@article {pmid40955050, year = {2025}, author = {Lake, ET and Tibbitt, CC and Iroegbu, C and Rizzo, JF and Smith, JG and Rogowski, JA}, title = {Including Nursing System Factors to Address Health Disparities: A Conceptual Framework.}, journal = {Inquiry : a journal of medical care organization, provision and financing}, volume = {62}, number = {}, pages = {469580251372763}, doi = {10.1177/00469580251372763}, pmid = {40955050}, issn = {1945-7243}, mesh = {Humans ; *Healthcare Disparities ; *Nursing Staff, Hospital/organization & administration ; Personnel Staffing and Scheduling ; *Health Status Disparities ; Workplace ; Social Determinants of Health ; }, abstract = {Nurses are the principal caregivers in acute care. Evidence links nursing to patient outcome disparities. Conceptual frameworks addressing health inequities, however, overlook nursing factors including staffing, work environment, and structural factors. This paper addresses this gap by presenting a framework postulating nursing system factors as contributors to inequities, distinguishing it from frameworks focusing mainly on individual or social determinants. The literature demonstrates that hospitals with better nurse staffing and work environments have lower mortality and complication rates, particularly among vulnerable populations. Additionally, nursing factors vary by hospital and correlate with patient racial composition and outcomes. Authoritative reports and frameworks on healthcare disparities from the National Academies of Sciences, Engineering, and Medicine and the National Institute on Minority Health and Health Disparities were reviewed. The role of nursing in each was summarized. Kilbourne et al.'s framework was adapted to propose that disparities in patient outcomes are shaped by the organizational context of nursing, for example, nurse staffing, work environment, structural competence, and the patient-nurse clinical encounter. Nursing's impact on equitable care and outcomes should be central to health disparity frameworks. This framework implies that policymakers include nursing elements in equity performance measures and incentivize them through payment systems. Administrators should consider nursing system features as integral to equitable care. Research on the framework assertions is warranted to inform health equity strategies through nursing. By highlighting mechanisms through which nursing factors contribute to disparities, this framework motivates health equity research and policy in acute care settings.}, } @article {pmid40952592, year = {2025}, author = {Chen, C and Wang, GQ and Li, DD and Zhang, F}, title = {Microbiota-gut-brain axis in neurodegenerative diseases: molecular mechanisms and therapeutic targets.}, journal = {Molecular biomedicine}, volume = {6}, number = {1}, pages = {64}, pmid = {40952592}, issn = {2662-8651}, support = {No. 82160690//National Natural Science Foundation of China/ ; No. ZK [2021]-014//Science and Technology Foundation of Guizhou Province/ ; No. 2020-39//Collaborative Innovation Center of Chinese Ministry of Education/ ; }, mesh = {Humans ; *Neurodegenerative Diseases/therapy/microbiology/metabolism/etiology ; *Gastrointestinal Microbiome ; *Brain/metabolism ; Animals ; Dysbiosis ; Probiotics/therapeutic use ; *Brain-Gut Axis ; }, abstract = {The microbiota-gut-brain axis (MGBA) is an intricate bidirectional communication network that links intestinal microbiota with the central nervous system (CNS) through immune, neural, endocrine, and metabolic pathways. Emerging evidence suggests that dysregulation of the MGBA plays pivotal roles in the onset and progression of neurodegenerative diseases. This review outlines the key molecular mechanisms by which gut microbes modulate neuroinflammation, blood-brain barrier integrity, protein misfolding, and neuronal homeostasis. We discuss how microbial metabolites, such as short-chain fatty acids, tryptophan derivatives, and bile acids, interact with host to influence CNS functions. Disease-specific features are described across Alzheimer's disease, Parkinson's disease, Multiple sclerosis, and Amyotrophic lateral sclerosis, emphasizing the distinct and overlapping pathways through which gut dysbiosis may contribute to pathogenesis. We further explore the translational potential of microbiota-targeted therapies, including probiotics, fecal microbiota transplantation, dietary interventions, and small-molecule modulators. While preclinical results are promising, clinical trials reveal considerable variability, highlighting the need for personalized approaches and robust biomarkers. Challenges remain in deciphering causal relationships, accounting for inter-individual variability, and ensuring reproducibility in therapeutic outcomes. Future research should integrate multi-omics strategies, longitudinal human cohorts, and mechanistic models to clarify the role of the MGBA in neurodegeneration. Collectively, understanding the MGBA provides a transformative perspective on neurodegenerative disease mechanisms and offers innovative therapeutic avenues that bridge neurology, microbiology, and precision medicine.}, } @article {pmid40952318, year = {2025}, author = {Guo, L and Xu, IQ and Nag, S and Xu, J and Chai, J and Simmons, Z and Ramasamy, S and Yeo, CJJ}, title = {Predicting Amyotrophic Lateral Sclerosis Mortality With Machine Learning in Diverse Patient Databases.}, journal = {Muscle & nerve}, volume = {72}, number = {4}, pages = {653-661}, pmid = {40952318}, issn = {1097-4598}, support = {C210112024//A*STAR Career Development Award (CDA)/ ; IRNMR21CPGJJ//National Neuroscience Institute (NNI) Pilot/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/mortality/diagnosis ; *Machine Learning ; Male ; Databases, Factual ; Female ; Middle Aged ; Aged ; Prognosis ; Predictive Value of Tests ; Adult ; }, abstract = {INTRODUCTION: Predicting mortality in Amyotrophic Lateral Sclerosis (ALS) guides personalized care and clinical trial optimization. Existing statistical and machine learning models often rely on baseline or diagnosis visit data, assume fixed predictor-survival relationships, lack validation in non-Western populations, and depend on features like genetic tests and imaging not routinely available. This study developed ALS mortality prediction models that address these limitations.

METHODS: We trained Royston-Parmar and eXtreme Gradient Boosting models on the PRO-ACT database for 6- and 12-month mortality predictions. Each visit was labeled positive (for death) if death occurred within 6 or 12 months, negative if survival was confirmed beyond that, and excluded if follow-up was insufficient, assuming patients were alive up to their last recorded visit. Models were validated on independent datasets from the North American Celecoxib trial and a Singapore ALS clinic population. Feature importance and the impact of reducing predictors on performance were evaluated.

RESULTS: Models predicted mortality from any clinical visit with area under the curve (AUC) of 0.768-0.819, rising to 0.865 for 12-month prediction using 3-month windows. Albumin was the top predictor, reflecting nutritional and inflammatory status. Other key predictors included ALS Functional Rating Scale-Revised slope, limb onset, absolute basophil count, forced vital capacity, bicarbonate, body mass index, and respiratory rate. Models maintained robust performance on the independent datasets and after reducing inputs to seven key predictors.

DISCUSSION: These visit-agnostic models, validated across diverse populations, identify key prognostic features and demonstrate the potential of predictive modeling to enhance ALS care and trial design.}, } @article {pmid40952044, year = {2025}, author = {Gao, Y and Brothwood, JL and Saini, H and O'Sullivan, GA and Bento, CF and McCarthy, JM and Wallis, NG and Di Daniel, E and Graham, B and Tams, DM}, title = {Altered Inflammatory Signature in a C9ORF72-ALS iPSC-Derived Motor Neuron and Microglia Coculture Model.}, journal = {Glia}, volume = {}, number = {}, pages = {}, doi = {10.1002/glia.70084}, pmid = {40952044}, issn = {1098-1136}, support = {//Astex Pharmaceuticals/ ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a complex neurodegenerative disorder involving multiple cell types in the central nervous system. The key pathological features of ALS include the degeneration of motor neurons and the initiation and propagation of neuroinflammation mediated by nonneuronal cell types such as microglia. Currently, the specific mechanisms underlying the involvement of microglia in neuroinflammation in ALS are unclear. Consequently, we generated several human-induced pluripotent stem cell (iPSC) derived motor neuron and microglia cocultures. We utilized ALS patient-derived iPSCs carrying a common genetic variant, the hexanucleotide repeat expansion (HRE) in C9ORF72, as well as C9ORF72 knockout (KO) iPSC lines. iPSC-derived motor neurons and microglia demonstrated expression of cell type-specific markers and were functional. Phenotypic assessments on motor neurons and microglia in mono- and cocultures identified dysfunction in the expression and secretion of inflammatory cytokines and chemokines in lipopolysaccharide (LPS)-stimulated C9ORF72 HRE and C9ORF72 KO microglia. Analysis of single-cell RNA sequencing data from microglia and motor neuron cocultures revealed cell type-specific transcriptomic changes. Specifically, we detected the removal of an LPS-responsive microglia subpopulation, correlating with a dampened inflammatory response in C9ORF72 HRE and C9ORF72 KO microglia. Overall, our results support the critical role of microglia-mediated neuroinflammation in ALS pathology, and our iPSC-derived models should prove a valuable platform for further mechanistic studies of ALS-associated pathways.}, } @article {pmid40951906, year = {2025}, author = {Telec, W and Al-Saad, S and Karbowski, L and Kłosiewicz, T and Baszko, A}, title = {Postshock Pacing in Cardiac Arrest: A Concise Review.}, journal = {Emergency medicine international}, volume = {2025}, number = {}, pages = {9067144}, pmid = {40951906}, issn = {2090-2840}, abstract = {Following an administered shock in cardiac arrest, the heart commonly experiences a short phase of inability to efficiently perfuse. Despite being a commonly used feature in the ICD population, postshock pacing (PSP) is yet to be adequately explored for its utility in this pulseless phase. Notably, an overwhelming proportion of available data for transcutaneous pacing in spontaneous cardiac arrest stem from the 1980s and 1990s and revolve largely around nonshockable, as opposed to shockable rhythms. The lack of large-scale clinical trials assessing the efficacy of transcutaneous PSP and the considerable advancements in technology and training facilities since the 1990s indicates a need for reevaluation of current understanding of PSP and its applicability in cardiac arrest. Shedding light into the possible implications of transcutaneous PSP in emergency setting cardiac arrest may not only reshape the current protocols of ALS but also carry the potential of improving survival rates. This concise review serves as a summary of the existing knowledge on the subject of PSP and reveals further possible directions for the development of this therapy.}, } @article {pmid40951286, year = {2025}, author = {Lill, C and Homann, J and Korologou-Linden, R and Viallon, V and Morgan, S and Dobricic, V and Deecke, L and Schessner, J and Smith-Byrne, K and Birtles, D and Zhao, Y and Wuu, J and Artaud, F and Hajizadah, F and Huerta, J and Ohlei, O and Lebedev, M and Kolijn, P and Eslava, MG and Jiménez-Zabala, A and Sánchez, MJ and Trobajo-Sanmartín, C and Colorado-Yohar, S and Alonso-Martin, S and Petrova, D and Sieri, S and Berger, K and Peters, S and Wareham, N and Kaaks, R and Travis, R and Vermeulen, R and Consortium, GNPCGN and Tzoulaki, I and Elbaz, A and Mann, M and Sacerdote, C and Masala, G and Katkze, V and Benatar, M and Bertram, L and Middleton, L and Riboli, E and Gunter, M and Robinson, O and Ferrari, P}, title = {Redefining ALS: Large-scale proteomic profiling reveals a prolonged pre-diagnostic phase with immune, muscular, metabolic, and brain involvement.}, journal = {Research square}, volume = {}, number = {}, pages = {}, doi = {10.21203/rs.3.rs-7452736/v1}, pmid = {40951286}, issn = {2693-5015}, abstract = {Background: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder with a largely unknown duration and pathophysiology of the pre-diagnostic phase, especially for the common non-monogenic form. Methods: We leveraged the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort with up to 30 years of follow-up to identify incident ALS cases across five European countries. Pre-diagnostic plasma samples from initially healthy participants underwent high-throughput proteomic profiling (7,285 protein markers, SomaScan). Cox proportional hazards models based on 4,567 participants (including 172 incident ALS cases) were used to identify protein biomarkers associated with future ALS diagnosis. Top results were indirectly validated in two independent case-control studies of prevalent ALS (n=417 ALS, 852 controls). Functional annotation included cross-disease comparisons, gene set and tissue enrichment testing, organ-specific proteomic clocks, and the application of large-language models (LLM). Findings: Five proteins (SECTM1, CA3, THAP4, KLHL41, SLC26A7) were identified as significant pre-diagnostic ALS biomarkers (FDR=0.05), detectable approximately two decades before diagnosis. Of these, all except SECTM1 were indirectly validated in independent cohorts of prevalent ALS cases, supporting their clinical significance. Additionally, 22 nominally significant (p<0.05) pre-diagnostic biomarkers were FDR-significant in prevalent ALS with consistent effect directions. Cross-disease comparisons with pre-diagnostic Parkinson's and Alzheimer's disease suggested a largely specific pre-diagnostic ALS biomarker signature. Gene ontology and tissue enrichment highlighted early involvement of immune, muscle, metabolic, and digestive processes. Furthermore, analyses of proteomic clocks revealed accelerated aging in brain-cognition, immune, and muscle tissues before clinical diagnosis. Druggability and LLM analyses revealed possible therapeutic targets and novel strategies, emphasizing translational relevance. Interpretation: Our study provides first evidence of ultra-early molecular changes in common ALS up to two decades prior to clinical onset, mainly affecting immune, muscle, metabolic, digestive, and cognitive systems. Our study nominates several compelling candidates for risk stratification studies and novel therapeutic targets for early intervention.}, } @article {pmid40950480, year = {2025}, author = {Wolff, AW and Leha, A and Koch, JC and Demleitner, AF and Neuwirth, C and Friede, T and Weber, M and Lingor, P}, title = {Fasudil attenuates disease spreading in ALS - a post-hoc analysis of the ROCK-ALS trial.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, doi = {10.1101/2025.09.02.25334770}, pmid = {40950480}, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by the spread of muscle weakness across body regions. The ROCK-ALS trial was a multicenter, randomized, double-blind, placebo-controlled phase 2 study assessing the safety, tolerability, and efficacy of the Rho kinase inhibitor fasudil as an add-on to riluzole in ALS patients. A key exploratory objective was to evaluate fasudil's effect on the spread of muscle weakness using the Motor Unit Number Index (MUNIX), a quantitative electrophysiological biomarker of lower motor neuron integrity. MUNIX was assessed in 10 muscles (5 on each body side) at baseline, day 26, day 90, and day 180. Correlations were assessed between baseline serum biomarkers-neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP)-and baseline clinical measures (ALSFRS-R, slow vital capacity, and MUNIX sum scores) as well as their monthly rates of change, to explore potential prognostic relationships. For the analysis of disease spreading, muscles were classified as newly affected based on MUNIX decline relative to contralateral values or prior measurements, using thresholds of ≥10%, ≥20%, or ≥30%. 118 participants were included in the intention-to-treat population, 78 had full MUNIX datasets at baseline and 67 had at least one follow-up. Baseline MUNIX sum scores correlated with subsequent ALSFRS-R decline, suggesting prognostic value. Additionally, at day 90, fasudil significantly reduced the number of newly affected muscles compared to placebo in a dose dependent manner over different thresholds. These findings support MUNIX as a sensitive biomarker for monitoring disease spreading and demonstrate that fasudil may attenuate the progression of lower motor neuron involvement in ALS.}, } @article {pmid40950010, year = {2025}, author = {De La Cruz, PM and Lockett, A and Gomes, MT and Banerjee, S and Razee, A and Fisher, A and Cook, T and Lloyd, CD and Magaki, S and Umar, S and Oblak, AL and Machado, RF}, title = {Pulmonary Hypertension Promotes Neuroinflammation and Neurodegeneration.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2025.09.02.673803}, pmid = {40950010}, issn = {2692-8205}, abstract = {INTRODUCTION: Pulmonary arterial hypertension (PAH) is associated with neurocognitive deficits and abnormal brain MRI. Little is known about the mechanisms underlying these clinical observations. TDP-43 is a proteinopathy associated with frontotemporal lobar degeneration (FTLD), Alzheimer's Disease, and Amyotrophic Lateral Sclerosis (ALS). In this study, we hypothesize PAH will result in gliosis, reduced neuronal density, and increased TDP-43 mislocalization.

METHODS: Sprague Dawley rats were randomly assigned to receive Vehicle (DMSO) Monocrotaline, or Sugen/Hypoxia to induce PH. Right heart catheterization was used to confirm PAH. Brain tissue was fixed and probed for microglia (Iba1), astrocytes (GFAP), neurons (NeuN), and TDP-43. Human PH vs control brain tissue was also probed for NeuN and TDP-43.

RESULTS AND CONCLUSIONS: We identify an increase in microglia and astrocyte density in the frontal cortex along with reduced neuronal density and neuronal TDP-43 mislocalization in rat models of PH. In addition, human PH frontal cortex demonstrated neuronal TDP-43 mislocalization. This is the first evidence of TDP-43 proteinopathy in PH.}, } @article {pmid40949955, year = {2025}, author = {Guo, C and Chen, K and Vatsavayai, SC and Akiyama, T and Zeng, Y and Liu, C and Sianto, O and Yang, E and Bombosch, J and Powell, R and Zhen, S and Mekhoubad, S and Morrie, RD and Miller, G and Green, EM and Petrucelli, L and Seeley, WW and Gitler, AD}, title = {Cryptic splicing in synaptic and membrane excitability genes links TDP-43 loss to neuronal dysfunction.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {40949955}, issn = {2692-8205}, abstract = {TDP-43 pathology is a defining pathological hallmark of multiple neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). A major feature of TDP-43 pathology is its nuclear depletion, leading to the aberrant inclusion of cryptic exons during RNA splicing. STMN2 and UNC13A have emerged as prominent TDP-43 splicing targets, but the broader impact of TDP-43-dependent cryptic splicing on neuronal function remains unclear. Here, we report new TDP-43 splicing targets critical for membrane excitability and synaptic function, including KALRN, RAP1GAP, SYT7 and KCNQ2 . Using human stem cell-derived neurons, we show that TDP-43 reduction induces cryptic splicing and downregulation of these genes, resulting in impaired excitability and synaptic transmission. In postmortem brains from patients with FTD, these cryptic splicing events occur selectively in neurons with TDP-43 pathology. Importantly, suppressing individual cryptic splicing events using antisense oligonucleotides partially restores neuronal function, and combined targeting almost fully rescues the synaptic deficit caused by TDP-43 loss. Together, our findings provide evidence that cryptic splicing in these synaptic and membrane excitability genes is not only a downstream marker but instead a direct driver of neuronal dysfunction, establishing a mechanistic link between TDP-43 pathology and neurodegeneration in ALS and FTD.}, } @article {pmid40949727, year = {2025}, author = {Gu, Q and Shen, J and Chu, S and Huang, Q and Chen, A and Li, L and Li, R}, title = {Analysis of the resistance level and target site resistance mechanisms of Echinochloa crus-galli to penoxsulam from Hubei Province, China.}, journal = {PeerJ}, volume = {13}, number = {}, pages = {e19973}, pmid = {40949727}, issn = {2167-8359}, abstract = {Echinochloa crus-galli is a grass weed that infests rice fields and causes significant crop yield losses. In this study, we surveyed 15 resistant E. crus-galli populations collected from rice fields in Hubei Province, China, and investigated the resistance levels and target site resistance mechanisms to the acetolactate synthase (ALS) inhibitor penoxsulam. The results of whole-plant bioassay experiments revealed that 15 populations presented different levels of resistance to penoxsulam. The Trp-574-Leu mutation was detected in ten resistant populations, and the Pro-197-Leu mutation was detected in one resistant population. Additionally, the in vitro ALS activity in resistant populations (18-ETF, 18-WJJ, and 18-WMJ) was 51.28-, 5.51-, and 8.46-fold greater than that in the susceptible population. The ALS from these resistant populations requires a much higher penoxsulam concentration for activity inhibition. ALS gene expression in three resistant populations (18-ETF, 18-WJJ, and 18-WMJ) was 1.53-, 1.58-, and 1.41-fold greater than that in the susceptible population 18-NJ before penoxsulam treatment. Our results indicated that target-site mutation in ALS is at least partially responsible for barnyardgrass resistance to penoxsulam in Hubei Province.}, } @article {pmid40949612, year = {2025}, author = {Gao, L and Wang, J and Bi, Y}, title = {Nanotechnology for Neurodegenerative Diseases: Recent Progress in Brain-Targeted Delivery, Stimuli-Responsive Platforms, and Organelle-Specific Therapeutics.}, journal = {International journal of nanomedicine}, volume = {20}, number = {}, pages = {11015-11044}, pmid = {40949612}, issn = {1178-2013}, abstract = {Neurodegenerative diseases-including Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis-are characterized by progressive neuronal loss and complex pathological mechanisms such as protein aggregation, mitochondrial dysfunction, and neuroinflammation. Conventional therapies offer limited efficacy due to the blood-brain barrier (BBB) and lack of targeted delivery. Nanotechnology has emerged as a transformative strategy for precise brain-targeted treatment. This review summarizes recent advances in nanoparticle-based drug delivery systems, including polymeric nanoparticles, liposomes, inorganic nanomaterials, and biomimetic carriers, highlighting their design features, BBB-penetration mechanisms, and disease-specific applications. Emphasis is placed on stimuli-responsive nanocarriers that react to pH, reactive oxygen species, or enzyme activity, enabling site-specific drug release. Additionally, organelle-targeting strategies-particularly those directed at mitochondria and lysosomes-are explored for their role in subcellular precision therapy. The integration of diagnostic and therapeutic modalities in theranostic nanoplatforms is also discussed. By consolidating preclinical progress and emerging technologies, this review offers insights into the future of nanomedicine in treating neurodegenerative diseases and lays the groundwork for clinical translation.}, } @article {pmid40949395, year = {2025}, author = {Han, S and Yu, LX and Zou, HP and Miao, YD and Lin, SX}, title = {Computed tomography-dominant surveillance strategies for colorectal cancer: Improving early detection of recurrence.}, journal = {World journal of gastrointestinal surgery}, volume = {17}, number = {8}, pages = {107340}, pmid = {40949395}, issn = {1948-9366}, abstract = {Colorectal cancer (CRC) is one of the most prevalent cancers globally, with a high recurrence rate following curative surgery, especially within the first 3 to 5 years. Post-surgical follow-up plays a vital role in detecting local and distant recurrences, significantly influencing survival rates. However, despite established guidelines recommending surveillance strategies, discrepancies persist regarding the optimal surveillance modality and patient adherence to follow protocols. Sala-Miquel et al's study emphasize the superiority of computed tomography in detecting metastasis and recurrence, while also shedding light on the critical role of adherence to surveillance protocols in improving patient outcomes. This editorial discusses the implications of these findings for clinical practice, providing a comprehensive overview of the current landscape of CRC surveillance and the path forward for improving patient outcomes.}, } @article {pmid40949365, year = {2025}, author = {Dai, JW and Xing, YX and Sun, NZ}, title = {Adjuvant chemotherapy for gallbladder cancer: Current evidence, controversies, and future directions.}, journal = {World journal of gastrointestinal surgery}, volume = {17}, number = {8}, pages = {108160}, pmid = {40949365}, issn = {1948-9366}, abstract = {Gallbladder cancer is an aggressive malignancy notorious for its poor prognosis and treatment challenges, even at early stages. In their recent work, Kim et al utilized data from the National Cancer Database to explore whether adding chemotherapy to surgical intervention could improve survival outcomes for patients diagnosed with stage II gallbladder cancer. The use of adjuvant chemotherapy following curative surgery in this patient population has been a long-standing source of debate. Historically, the lack of clear guidelines for managing stage II gallbladder cancer has resulted in inconsistent, sometimes contradictory findings from various studies regarding the effectiveness of postoperative chemotherapy. Consequently, many clinicians have relied on studies involving other biliary tract cancers to justify the routine use of prophylactic chemotherapy after surgery, aiming to minimize recurrence risk. Given the rarity, high mortality rate, and the small sample sizes typical in gallbladder cancer studies, Kim et al's contribution represents a significant and commendable effort to address these challenges. Kim et al designed a retrospective cohort study with well-defined inclusion criteria and clear treatment classifications. Notably, their findings suggested that in stage II gallbladder cancer, adjuvant chemotherapy did not yield a meaningful survival benefit over surgery alone. These results therefore casted doubt on the routine practice of administering chemotherapy to all patients postoperatively, prompted clinicians to reconsider their approach. Furthermore, this controversy directly influences clinical decisionmaking and guideline recommendations, as uncertainty regarding the benefit of adjuvant chemotherapy may lead to heterogeneous practices across different institutions and regions. This article critically assessed the research design, methodology, and clinical implications of the study by Kim et al. It also provided an in-depth exploration of the broader question regarding the appropriateness of adjuvant chemotherapy following surgery for stage II gallbladder cancer, highlighting the necessity of rigorous study designs to produce reliable evidence.}, } @article {pmid40949164, year = {2025}, author = {Roczkowsky, A and Rachubinski, RA and Hobman, TC and Power, C}, title = {Peroxisomes as emerging clinical targets in neuroinflammatory diseases.}, journal = {Frontiers in molecular neuroscience}, volume = {18}, number = {}, pages = {1642590}, pmid = {40949164}, issn = {1662-5099}, abstract = {Peroxisomes are membrane-bounded organelles that contribute to a range of physiological functions in eukaryotic cells. In the central nervous system (CNS), peroxisomes are implicated in several vital homeostatic functions including, but not limited to, reactive oxygen species signaling and homeostasis; generation of critical myelin sheath components (including ether phospholipids); biosynthesis of neuroprotective docosahexaenoic acid; breakdown of neurotoxic metabolites (such as very-long chain fatty acids); and, intriguingly, glial activation and response to inflammatory stimuli. Indeed, peroxisomes play a critical role in modulating inflammatory responses and are key regulators of the mitochondrial antiviral signaling (MAVS) protein-mediated response to infections. The importance of peroxisomes in CNS physiology is exemplified by the peroxisome biogenesis disorders (PBDs), a spectrum of inherited disorders of peroxisome assembly and/or abundance, that are characterized in part by neurological manifestations ranging from severe cerebral malformations to vision and hearing loss, depending on the individual disorder. Recently, peroxisome dysfunction has been implicated in neurological diseases associated with neuroinflammation including Alzheimer's disease, amyotrophic lateral sclerosis, multiple sclerosis, and Parkinson's disease while also contributing to the pathogenesis of neurotropic viruses including SARS-CoV-2, Human Pegivirus, HIV-1 and Zika virus. In the present review, we examine the diverse roles that peroxisomes serve in CNS health before reviewing more recent studies investigating peroxisome dysfunction in inflammatory brain disorders and also highlight potential peroxisomal targets for diagnostic biomarkers and therapeutic interventions.}, } @article {pmid40948263, year = {2025}, author = {Li, Y and Wang, JL and Ma, JJ and Sun, Z and Zhang, B}, title = {Bibliometric Analysis of Intelligent Ultrasound Imaging in the Diagnosis of Thyroid Nodules.}, journal = {Zhongguo yi xue ke xue yuan xue bao. Acta Academiae Medicinae Sinicae}, volume = {47}, number = {4}, pages = {590-600}, doi = {10.3881/j.issn.1000-503X.16324}, pmid = {40948263}, issn = {1000-503X}, abstract = {Objective To explore the research progress and hotspots of intelligent ultrasound imaging in the diagnosis of thyroid nodules and clarify the research directions via the bibliometric method.Methods The relevant research articles on intelligent ultrasound imaging in the diagnosis of thyroid nodules were retrieved from the Web of Science Core Collection,covering the period from January 2004 to August 2024.Python was used to analyze the number of annual publications.VOSviewer was used to create the co-occurrence network of authors and the keyword density map.CiteSpace was used to demonstrate the dual-map overlays of the journals,as well as the bursts and clustering of co-citations and keywords.Results A total of 1 179 articles were included.The annual number of publications increased steadily.The involved journals demonstrated high quality,and the publications showed a trend of cross-research.Chinese researchers were the core research force in this field.Haugen et al.'s study on the guidelines for thyroid nodules had the most citations.The clustering of co-citations and keywords indicated studies in multiple fields.Thyroid nodules,cancer,and deep learning were the representative keywords in this field.Conclusions The continuous enrichment of research topics promotes the rapid development of intelligent ultrasound imaging for thyroid nodules.Intelligent diagnosis methods based on deep learning can provide diagnostic suggestions,while there are still challenges such as interpretation.One of the research directions is the deep combination of intelligent diagnosis algorithms and medical knowledge.}, } @article {pmid40947692, year = {2025}, author = {Manubolu, K and Peeriga, R}, title = {Revolutionizing Neurodegenerative Disease Management: The Synergy of AI and Pharmacy.}, journal = {Current aging science}, volume = {}, number = {}, pages = {}, doi = {10.2174/0118746098375978250820220024}, pmid = {40947692}, issn = {1874-6128}, abstract = {Neurodegenerative diseases, including Alzheimer's, Parkinson's, and amyotrophic lateral sclerosis (ALS), represent major healthcare challenges worldwide. Despite advances in diagnosis and treatment, these conditions remain incurable, and there is a need for more effective management strategies. The integration of artificial intelligence (AI) in healthcare has emerged as a promising solution, offering new approaches to diagnosis, personalized treatment, and patient care. This paper explores the potential of AI to revolutionize the management of neurodegenerative diseases, with a focus on its synergistic role in pharmacy. By leveraging AI in drug discovery, personalized treatment plans, and clinical decision-making, AI can enhance therapeutic outcomes and improve patient quality of life. The study reviews the current landscape of AI applications in neurodegenerative disease management, with a focus on pharmacy-related interventions. The review includes AI-driven approaches in genomics, biomarkers, drug repurposing, and clinical trials. It also examines AI's role in optimizing pharmaceutical care, improving medication adherence, and tailoring treatments based on individual genetic profiles. AI has demonstrated its capability to analyze vast datasets, from genetic information to clinical records, to identify novel drug targets and predict patient responses to specific therapies. The use of AI in precision medicine has enabled more accurate diagnosis and has facilitated the development of personalized treatments for neurodegenerative diseases. Additionally, AI tools are enhancing medication management by providing personalized therapy adjustments and improving adherence. AI offers transformative potential for the future of neurodegenerative disease management. Its integration into pharmacy practice promises more effective, individualized treatments, accelerating drug discovery, and optimizing patient care. As AI technologies continue to advance, their role in managing complex neurological disorders will become increasingly vital.}, } @article {pmid40946454, year = {2025}, author = {Taussig, D and Dussaule, C and Jacquemin, E and Almes, M and Bouilleret, V and Sébille, V}, title = {Electroencephalogram in children with hepatic encephalopathy: towards a new classification?.}, journal = {Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology}, volume = {179}, number = {}, pages = {2111000}, doi = {10.1016/j.clinph.2025.2111000}, pmid = {40946454}, issn = {1872-8952}, abstract = {OBJECTIVE: Diagnosis of hepatic encephalopathy (HE) is challenging in children. The electroencephalogram (EEG) is an easily accessible and pivotal tool but no satisfactory classification is currently available.

METHODS: We studied inter-observer agreement with Gwet's AC2 coefficient with quadratic weights, for Navelet et al.'s (1990) classification (1990) in EEGs successively performed for chronic or acute liver disease in a reference centre. We analysed reasons for discordance and proposed a new classification. We studied the association between both classification, the neurological impairment and hepatic biological dysfunction.

RESULTS: 171 EEGs were analysed. Slowing of the dominant rhythm and loss of reactivity characterized the pathological awake EEGs. Using the Navelet classification, there was a very high inter-rater agreement beyond chance. We have refined it with Children's Hepatic Encephalopathy EEG Recording Scale (CHEERS). Inter-rater agreement for the CHEERS classification in 27 supplementary EEGs was almost perfect beyond chance. Association between each EEG scale and the neurological impairment and hepatic biological dysfunction was significant.

CONCLUSION: Our proposed classification is reliable in detailing abnormalities when suspecting HE in children.

SIGNIFICANCE: The next step will be to validate the classification in an external cohort by independent readers and to prove its utility in detecting the first stages of deterioration of hepatic function.}, } @article {pmid40946250, year = {2025}, author = {Zhu, J and Zhang, Y and Hu, S and He, X and Hong, X and Wei, W and Shu, S and Zhou, H and Yang, G and Zhang, H}, title = {Evaluating the predictive potential of Th1 (IFN-γ[+]CD4[+])/CD4[+] in rapidly progressive amyotrophic lateral sclerosis.}, journal = {Journal of neurology}, volume = {272}, number = {9}, pages = {631}, pmid = {40946250}, issn = {1432-1459}, support = {2025HZZD09//The Construction Fund of Key Medical Disciplines of Hangzhou - Rare Disease (Motor Neuron Disease)/ ; 2025KY1187//Zhejiang Provincial Medical and Health Science and Technology Project/ ; }, abstract = {BACKGROUND: Th1 (IFN-γ[+]CD4[+])/CD4[+] cells exacerbate the release of pro-inflammatory cytokines, contributing to neuronal death. It is proposed that the peripheral immune system plays a pivotal role in the pathophysiology of amyotrophic lateral sclerosis (ALS). This study aims to develop an interpretable machine learning model based on blood Th1/CD4[+] cells to predict rapidly progressive ALS.

METHODS: We enrolled 564 patients with sporadic ALS who met the eligibility inclusion criteria for further analysis. Immune cells and cytokines were quantified using flow cytometric cell counting and a flow cytometry-based fluorescent bead capture assay. Multivariate Cox proportional hazards models and restricted cubic spline analyses were applied to estimate the correlation between Th1/CD4[+] cells and rapidly progressive ALS. The important variables identified through LASSO regression analysis were incorporated into the development of the machine learning model.

RESULTS: The multivariate Cox proportional hazards model revealed that, compared to the low Th1/CD4[+] group (Th1/CD4[+]  < 16.21), the high Th1/CD4[+] group (Th1/CD4[+]  ≥ 16.21) was positively associated with the rate of ALS progression (HR: 1.90, 95% CI: 1.34-2.70). Th1/CD4[+] is also associated with the decline in forced vital capacity (r = 0.11, P = 0.01). The machine learning model was built using Th1/CD4[+] in combination with the other 4 features. Xgboost performed best in the validation cohort, achieving an AUC of 0.804 and a G mean of 0.756.

CONCLUSIONS: Th1/CD4[+] (with an optimal cutoff value of 16.21) was established as an independent risk factor for rapid progression in ALS. The machine learning model incorporating Th1/CD4[+] demonstrated strong predictive performance.

TRIAL REGISTRATION: The prospective cohort study is registered with the Chinese Clinical Trial Registry (ID: ChiCTR2400079885) (http://www.chictr.org.cn/).}, } @article {pmid40945542, year = {2025}, author = {Kollstrøm, AM and Grønlie, MB and Christiansen, N and Sandvig, A and Sandvig, I}, title = {Induced long-term potentiation improves synaptic stability and restores network function in ALS motor neurons.}, journal = {Neurobiology of disease}, volume = {}, number = {}, pages = {107077}, doi = {10.1016/j.nbd.2025.107077}, pmid = {40945542}, issn = {1095-953X}, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease causing progressive dysfunction and degeneration of upper and lower motor neurons. An increasing body of evidence has identified synaptic alterations in patients and experimental models of ALS. Importantly, these have been associated with functional impairments in motor neuron networks, suggesting that synaptic impairments are early events in the disease cascade resulting in functional compensatory reconfigurations. The synapse may therefore represent a disease-modifying target to delay disease progression. In this study, we aimed to stabilize synapses and modify structural connectivity to restore network balance in ALS patient-derived motor neuron networks. To this end, we blocked the potassium channels using tetraethylammonium (TEA) which has been shown to induce chemical long-term potentiation (cLTP). The unperturbed ALS patient-derived motor neuron networks developed clear signs of subtle network dysfunction, including increased firing rate and bursting, and accompanying structural abnormalities. These features were partially restored by temporarily blocking the potassium channels. Specifically, the TEA-treated ALS networks were characterized by a reduction in aberrant branching and stabilization of dendritic spines, alongside a temporary reduction in firing rate and bursting. Furthermore, protein expression assays revealed restoration of dysregulated molecular pathways, including protein synthesis and metabolic pathways, and upregulation of pathways involved in synapse organization in the TEA-treated ALS networks. This is one of the first studies to integrate synaptic potentiation, proteomics, and functional network analysis of human ALS motor neurons. Collectively, these findings improve our understanding of the association between synaptic impairments and functional alterations in ALS, and demonstrate the therapeutic potential of targeting neuronal excitability and plasticity to promote network balance.}, } @article {pmid40945007, year = {2025}, author = {Wang, X and Cui, T and Zhang, Y and Zhu, X and Li, H}, title = {Theoretical study on the modulation of ESIPT and AIE synergistic mechanisms in α-CAS fluorescent probe by binary solvents with contrasting polarity.}, journal = {Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy}, volume = {346}, number = {}, pages = {126920}, doi = {10.1016/j.saa.2025.126920}, pmid = {40945007}, issn = {1873-3557}, abstract = {Integrating Excited-State Intramolecular Proton Transfer (ESIPT) and Aggregation-Induced Emission (AIE) mechanism is central to achieving high sensitivity in luminescent materials. Based on Chen et al.'s experimental study, this work theoretically investigates the ESIPT and AIE properties of the α-CAS molecule in two mixed solvent systems (water/tetrahydrofuran (THF) and n-hexane/THF), revealing the mechanism by which the solvent environment regulates different AIE emission behavior. Analyses of potential energy curves (PECs), infrared spectra (IR), and radiative decay rates (Kr) confirmed the occurrence of ESIPT and pronounced AIE characteristics. Furthermore, electron-hole distribution analysis revealed a twisted intramolecular charge transfer (TICT) process, indicating that the luminescence of α-CAS is governed by the combined effects of multiple photophysical mechanisms. Notably, in the water/THF system, increasing the water content gradually enhances the polarity of the binary solution, thereby promoting the ESIPT and TICT processes. This leads to pronounced AIE behavior characterized by dominant enol* state fluorescence emission. In contrast, in the n-hexane/THF system, a rising n-hexane proportion gradually reduces solution polarity, suppressing ESIPT and TICT processes and resulting in AIE emission primarily driven by the keto* state. These results provide critical insights into the solvent environment's regulatory role in modulating the ESIPT, TICT, and AIE behaviors of α-CAS, establishing a robust theoretical framework for the design of multi-mode responsive fluorescent probes and highlighting their significant potential for diverse applications.}, } @article {pmid40944932, year = {2025}, author = {Drouin, E and Hautecoeur, P and Kwiatkowski, A}, title = {Jean-Martin Charcot and the Clinical Foundations of Amyotrophic Lateral Sclerosis: A Historical Case Revisited.}, journal = {European neurology}, volume = {}, number = {}, pages = {1-8}, doi = {10.1159/000548249}, pmid = {40944932}, issn = {1421-9913}, abstract = {We revisit a landmark clinical case recorded by Jean-Martin Charcot in 1877-78, describing a patient with bulbar-onset amyotrophic lateral sclerosis (ALS). This case offers a rich window into Charcot's observational method, clinical reasoning, and early neuropathological insights. We discuss the methodological rigor of Charcot's case analysis and place it in dialogue with modern understandings of ALS pathophysiology, diagnosis, and care. This historical reflection highlights how 19th-century neurology laid the foundation for current multidisciplinary approaches to managing neurodegenerative diseases.}, } @article {pmid40944442, year = {2025}, author = {Brown, A and Stubberfield, C and Vieira, F and Bedlack, R}, title = {Examining IGFBP7 as a potential therapeutic target in people with ALS.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {}, number = {}, pages = {1-4}, doi = {10.1080/21678421.2025.2559441}, pmid = {40944442}, issn = {2167-9223}, abstract = {A single nucleotide variant in an insulin-like growth factor (IGFBP7) promotor, which reduces IGFBP7 levels in brain, was previously associated with an ALS "reversal" phenotype. This raises the question of whether IGFBP7 might be a therapeutic target in ALS. Here, we use a combinatorial analysis to show that IGFBP7-Antisense (AS1) is associated with resistance to ALS. In ALS patients' blood, we demonstrate increased IGFPB7 protein relative to healthy controls. In ALS patients' spinal cords and iPS-derived motor neurons, we demonstrate increased IGFBP7 mRNA levels relative to healthy controls. These four new analyses support IGFBP7 as a possible therapeutic target in ALS.}, } @article {pmid40943950, year = {2025}, author = {Pochhammer, J and Kiani, S and Hobbensiefken, H and Hobbensiefken, H and Reichert, B and Taivankhuu, T and Becker, T and Gundlach, JP}, title = {Lactate in Drainage Fluid to Predict Complications in Robotic Esophagectomies-A Pilot Study in a Matched Cohort.}, journal = {Journal of clinical medicine}, volume = {14}, number = {17}, pages = {}, pmid = {40943950}, issn = {2077-0383}, abstract = {Background/Objectives: Despite advances in minimally invasive procedures, anastomotic leakages (ALs) after esophageal resections mark the most feared complication. Its early detection can lead to quick interventional treatment with improved survival. Nonetheless, early detection remains challenging, and scores are imprecise and complex. Methods: In our study we analyzed mediastinal drainage fluid to find parameters suggesting AL even before it became clinically evident and correlated them to routine biomarkers. All patients with AL after robotically assisted esophageal resections were included and matched 1:1 with uneventful controls. Additionally, transhiatal distal esophageal resections operated during this period were included. Drainage fluid was collected on postoperative days (PODs) 1-4 with consecutive blood gas analysis. Test quality was determined by the area under the curve (AUC) of the receiver operating characteristic curve (ROC). Results: In total, 40 patients were included, with 17 developing AL. There were no significant differences in gender, age, BMI or oncological treatment. The 30-day morbidity rate was 65.0%. The study was restricted to events in the first 12 days. While lactate value in drainage fluid differed significantly from POD 3 onwards in the two groups, serum CRP remained without significant differences. We developed the LacCRP score (CRP/30 + lactate/2). The AUC on POD 3 was 0.96, with a sensitivity and specificity of 100% and 75%, respectively. An estimator of 1.08 was found in multivariate analysis: one-point increase in the LacCRP score increases AL probability by 8%. Conclusions: This study demonstrates that postoperative lactate determinations in drainage fluid can predict AL after esophageal resection, and its combination with serum CRP results in a reliable LacCRP score.}, } @article {pmid40943639, year = {2025}, author = {Paniagua-Contreras, GL and Cano-Kobayashi, A and Fernández-Presas, AM and Ruíz-De la Cruz, M and Martínez-Gregorio, H and Vaca-Paniagua, F and Monroy-Pérez, E}, title = {Candida albicans Associated with Periodontal Disease Exhibits Different Clusters of Adhesion Gene and Protease Expression.}, journal = {International journal of molecular sciences}, volume = {26}, number = {17}, pages = {}, pmid = {40943639}, issn = {1422-0067}, abstract = {C. albicans has recently been described as a secondary colonizer associated with periodontal infections. This study aimed to determine the expression patterns of ALS and SAP family genes in C. albicans strains isolated from patients with periodontal disease (n = 268), and a control group of healthy individuals without any clinical signs of periodontal disease (n = 100) was included. C. albicans and the ALS and SAP genes were identified using polymerase chain reaction (PCR). An in vitro infection model was used with the strains using the human gingival fibroblast cell line. RNA was extracted using a QIAcube robotic workstation (Qiagen). A QuantiTect Reverse Transcription Kit (Qiagen) was used for first-strand cDNA synthesis. ALS and SAP gene expression in the strains was determined using real-time PCR. A total of 82.5% (n = 66) of the C. albicans strains were isolated from patients with moderate periodontitis, 10% (n = 8) from patients with chronic periodontitis, and 7.5% (n = 6) from patients with gingivitis. In the group of healthy individuals, C. albicans was identified in 9% (9/100). Overall, the most frequently expressed ALS genes in the strains from the three diagnoses were ALS1 (77/80), ALS3 (67/80), ALS4 (67/80), ALS6 (77/80), ALS7 (62/80), and ALS9 (73/80), while the most frequently expressed SAP genes were SAP1 (76/80), SAP6 (57/80), SAP9 (78/80), and SAP10 (77/80). The overall frequencies of expression of the ALS4, ALS9, SAP2, SAP3, SAP6, and SAP genes in the strains were statistically different across the three diagnoses. We identified different profiles of expression of the ALS and SAP genes in the strains of C. albicans that contribute directly to the degree of periodontal disease. Therefore, our findings may contribute to improving our knowledge of the molecular mechanisms of C. albicans in the pathogenesis of periodontal disease.}, } @article {pmid40943341, year = {2025}, author = {Yang, EJ}, title = {The Emerging Role of the Brain-Gut Axis in Amyotrophic Lateral Sclerosis: Pathogenesis, Mechanisms, and Therapeutic Perspectives.}, journal = {International journal of molecular sciences}, volume = {26}, number = {17}, pages = {}, pmid = {40943341}, issn = {1422-0067}, support = {(KIOM) KSN2224011//KIOM/ ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive loss of motor neurons. Although genetic and environmental factors are established contributors, recent research has highlighted the critical role of the gut-brain axis (GBA) in ALS pathogenesis. The GBA is a bidirectional communication network involving neural, immune, and endocrine pathways that connect the gut microbiota with the central nervous system. Dysbiosis in ALS disrupts this axis, leading to increased intestinal permeability, neuroinflammation, and excitotoxicity. Notably, reductions in butyrate-producing bacteria, alterations in microbial metabolites, and enhanced NLRP3 inflammasome activation have been observed in patients with ALS. These changes may precede motor symptoms, suggesting a potential causative role. Interventions targeting the microbiome, such as dietary modulation, have shown promise in delaying disease onset and reducing inflammation. However, the clinical evidence remains limited. Given that gut dysbiosis may precede neurological symptoms, microbiota-targeted therapies offer a novel and potentially modifiable approach to ALS treatment. Understanding the role of GBA in ALS will open new avenues for early diagnosis and intervention. Further clinical trials are required to clarify the causal links and evaluate the efficacy of microbiome-based interventions. Understanding the brain-gut-microbiota axis in ALS could lead to new diagnostic biomarkers and therapeutic strategies.}, } @article {pmid40943213, year = {2025}, author = {Liu, D and Yu, S and Ji, B and Peng, Q and Gao, J and Zhang, J and Guo, Y and Hu, M}, title = {Molecular Mechanisms of Herbicide Resistance in Rapeseed: Current Status and Future Prospects for Resistant Germplasm Development.}, journal = {International journal of molecular sciences}, volume = {26}, number = {17}, pages = {}, pmid = {40943213}, issn = {1422-0067}, support = {2023ZD0404203//Science and Technology Innovation 2030 Major Program/ ; 31901503//National Natural Science Foundation of China/ ; CARS-12//Agriculture Research System of China/ ; CX (23) 1001//Jiangsu Provincial Agricultural Science and Technology Independent Innovation Fund/ ; BE2021405//Jiangsu Province Key Research and Development Project/ ; }, abstract = {Rapeseed (Brassica napus) is a globally important oilseed crop whose yield and quality are frequently limited by weed competition. In recent years, there have been significant advances in our understanding of herbicide-resistance mechanisms in rapeseed and in the development of herbicide-resistant rapeseed germplasm. Here, we summarize the molecular mechanisms of resistance to three herbicides: glyphosate, glufosinate, and acetolactate synthase (ALS) inhibitors. We discuss progress in the identification of new resistance genes and the development of herbicide-resistant rapeseed germplasm, from the initial identification of natural mutants to artificial mutagenesis screening, introduction of exogenous resistance genes, and gene editing. In addition, we describe how synthetic biology and directed protein evolution will contribute to precision-breeding efforts in the near future. This is the first review to systematically integrate non-target resistance mechanisms and the potential applications of multi-omics and AI technologies for breeding of herbicide-resistant rapeseed, together with strategies for managing the risks associated with gene flow, the evolution of herbicide-resistant weeds, and the occurrence of volunteer plants resulting from deployment of herbicide-resistant rapeseed. By synthesizing current knowledge and future trends, this review provides guidance for safe, effective, and innovative approaches to the sustainable development of herbicide-resistant rapeseed.}, } @article {pmid40943143, year = {2025}, author = {Calcagnile, M and Alifano, P and Damiano, F and Pontieri, P and Del Giudice, L}, title = {A Perspective on the Role of Mitochondrial Biomolecular Condensates (mtBCs) in Neurodegenerative Diseases and Evolutionary Links to Bacterial BCs.}, journal = {International journal of molecular sciences}, volume = {26}, number = {17}, pages = {}, doi = {10.3390/ijms26178216}, pmid = {40943143}, issn = {1422-0067}, support = {project 'NutrAge' (project nr. 7022)//CNR-DISBA/ ; FOE-2019 DBA.AD003.139//CNR/ ; }, abstract = {Biomolecular condensates (BCs), formed through liquid-liquid phase separation (LLPS), are membraneless compartments that dynamically regulate key cellular processes. Beyond their canonical roles in energy metabolism and apoptosis, Mitochondria harbor distinct BCs, including mitochondrial RNA granules (MRGs), nucleoids, and degradasomes, that coordinate RNA processing, genome maintenance, and protein homeostasis. These structures rely heavily on proteins with intrinsically disordered regions (IDRs), which facilitate the transient and multivalent interactions necessary for LLPS. In this review, we explore the composition and function of mitochondrial BCs and their emerging involvement in neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, Amyotrophic lateral sclerosis, and Huntington's disease. We provide computational evidence identifying IDR-containing proteins within the mitochondrial proteome and demonstrate their enrichment in BC-related functions. Many of these proteins are also implicated in mitochondrial stress responses, apoptosis, and pathways associated with neurodegeneration. Moreover, the evolutionary conservation of phase-separating proteins from bacteria to mitochondria underscores the ancient origin of LLPS-mediated compartmentalization. Comparative analysis reveals functional parallels between mitochondrial and prokaryotic IDPs, supporting the use of bacterial models to study mitochondrial condensates. Overall, this review underscores the critical role of mitochondrial BCs in health and disease and highlights the potential of targeting LLPS mechanisms in the development of therapeutic strategies.}, } @article {pmid40940798, year = {2025}, author = {Li, L and Zheng, X and Ma, H and Zhu, M and Li, X and Sun, X and Feng, X}, title = {TREM2 in Neurodegenerative Diseases: Mechanisms and Therapeutic Potential.}, journal = {Cells}, volume = {14}, number = {17}, pages = {}, doi = {10.3390/cells14171387}, pmid = {40940798}, issn = {2073-4409}, abstract = {Neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS), represent significant global health challenges, affecting millions and straining healthcare systems. These disorders involve progressive neuronal loss and cognitive decline, with incompletely elucidated underlying mechanisms. Chronic neuroinflammation is increasingly recognized as a critical contributor to disease progression. The brain's resident immune cells, microglia, are central to this inflammatory response. When overactivated, microglia and other immune cells, such as peripheral macrophages, can exacerbate inflammation and accelerate disease development. Triggering Receptor Expressed on Myeloid Cells 2 (TREM2) is a transmembrane receptor of the immunoglobulin superfamily that demonstrates high expression on microglia in the central nervous system. TREM2 serves a vital role in regulating phagocytosis, synaptic pruning, and energy metabolism. This review examines the functions of TREM2 in neurodegenerative diseases and its potential as a therapeutic target, aiming to inform future treatment strategies.}, } @article {pmid40940752, year = {2025}, author = {Lee, JH and Chang, W and Min, SS and Song, DY and Yoo, HI}, title = {Beyond Support Cells: Astrocytic Autophagy as a Central Regulator of CNS Homeostasis and Neurodegenerative Diseases.}, journal = {Cells}, volume = {14}, number = {17}, pages = {}, doi = {10.3390/cells14171342}, pmid = {40940752}, issn = {2073-4409}, support = {2023//Eulji University/ ; RS-2024-00438628//Korea Health Industry Development Institute/Republic of Korea ; }, abstract = {Autophagy is a fundamental catabolic pathway critical for maintaining cellular homeostasis in the central nervous system (CNS). While neuronal autophagy has been extensively studied, growing evidence highlights the crucial roles of astrocytic autophagy in CNS physiology and pathology. Astrocytes regulate metabolic support, redox balance, and neuroinflammatory responses. These functions are closely linked to autophagic activity. The disruption of astrocytic autophagy contributes to synaptic dysfunction, chronic inflammation, myelin impairment, and blood-brain barrier instability. Dysregulation of astrocytic autophagy has been implicated in the pathogenesis of multiple neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. This review summarizes the molecular mechanisms of autophagy in astrocytes and delineates its role in intercellular communication with neurons, microglia, oligodendrocytes, and endothelial cells. Furthermore, we will discuss current pharmacological approaches targeting astrocytic autophagy, with particular attention to repurposed agents such as rapamycin, lithium, and caloric restriction mimetics. Although promising in preclinical models, therapeutic translation is challenged by the complexity of autophagy's dual roles and cell-type specificity. A deeper understanding of astrocytic autophagy and its crosstalk with other CNS cell types may facilitate the development of targeted interventions for neurodegenerative diseases.}, } @article {pmid40940730, year = {2025}, author = {Graber, DJ and Cook, WJ and Sentman, ML and Murad-Mabaera, JM and Stommel, EW and Sentman, CL}, title = {Human CAR Tregs Targeting SOD1 and Expressing BDNF Reduce Inflammation and Delay Disease in G93A hSOD1-NSG Mice.}, journal = {Cells}, volume = {14}, number = {17}, pages = {}, doi = {10.3390/cells14171318}, pmid = {40940730}, issn = {2073-4409}, support = {NS102556,//NIH NINDS/ ; NS117895//NIH NINDS/ ; NS132666//NIH NINDS/ ; }, abstract = {Regulatory T cells (Tregs) have anti-inflammatory immunomodulatory activity and hold therapeutic potential for chronic neuroinflammatory neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS). We are developing engineered human Tregs with enhanced disease-modifying activity for treating ALS. A combination of a disease-specific chimeric antigen receptor (CAR) recognizing misfolded human superoxide dismutase-1 (hSOD1) and constitutive expression of brain-derived neurotrophic factor (BDNF) was tested. The scFv region of CAR demonstrated binding to anterior horn tissues of ALS patients with and without familial ALS mutations in SOD1. Tregs transduced to express BDNF showed the ability to secrete BDNF and protect co-cultured neuronal cells from peroxidase toxicity. Co-expression of BDNF did not inhibit CAR Treg expansion, Treg markers, or CAR-mediated anti-inflammatory cytokine production. Human Tregs co-expressing CAR and BDNF were tested for activity in G93A hSOD1-NSG transgenic mice, which develop an early-onset and aggressive ALS-like disease and do not reject human cells. Human Tregs expressing CAR and BDNF delayed the onset of disease development, extended survival, and decreased spinal cord neuroinflammation. The engineered Tregs showed enhanced disease-modifying activity and hold promise as a therapy for ALS.}, } @article {pmid40940222, year = {2025}, author = {Poulin-Brière, A and Pozzi, S and Julien, JP}, title = {Antibody targeting TDP-43 mitigates pathogenic pathways induced by the cerebrospinal fluid of ALS.}, journal = {Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics}, volume = {}, number = {}, pages = {e00737}, doi = {10.1016/j.neurot.2025.e00737}, pmid = {40940222}, issn = {1878-7479}, abstract = {Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease characterized by the cytoplasmic mislocalization and accumulation of TAR DNA binding protein 43 (TDP-43). We reported previously the protective effects in a transgenic mouse model expressing ALS-linked mutant TDP-43[A315T] of a monoclonal antibody, called E6, binding specifically to the RNA Recognition Motif 1 (RRM1) domain of TDP-43. Here, we tested the effects of E6 antibody in an animal model of sporadic ALS based on the intracerebroventricular (i.c.v.) infusion during 14 days of cerebrospinal fluid (CSF) from sporadic ALS patients into transgenic mice expressing human TDP-43[WT]. Either intrathecal (i.t.) or i.c.v. injection of E6 antibody conferred protective effects in this model of disease. Thus, the CSF-inoculated E6 antibody reduced motor and cognitive impairments, mitigated TDP-43 proteinopathy and prevented neurofilament (Nf) disorganization in cortical and spinal neurons. Administration of E6 antibody reduced the loss of motor neurons in the spinal cord and the denervation of neuromuscular junctions. Moreover, E6 antibody promoted a switch toward features associated with a protective phenotype of microglial activation characterized by enhanced phagocytic function and reduced secretion of pro-inflammatory cytokines. The results suggest that an immunotherapy targeting the RRM1 domain of TDP-43 may confer protection against pathogenic pathways triggered by the CSF of ALS patients.}, } @article {pmid40939256, year = {2025}, author = {Novo-Rigueiro, M and Crespo-De, A and Antelo-Pose, A and Novo-Veleiro, I}, title = {[Shoulder pain as a preceding symptom in amyotrophic lateral sclerosis: A retrospective descriptive and exploratory study].}, journal = {Rehabilitacion}, volume = {59}, number = {4}, pages = {100932}, doi = {10.1016/j.rh.2025.100932}, pmid = {40939256}, issn = {1578-3278}, } @article {pmid40938412, year = {2025}, author = {Cantré, D and König, J and Makowsky, C and Dyrba, M and Prudlo, J}, title = {Midsagittal Midbrain Area and Midbrain-to-Pons-Ratio Cannot Distinguish Overlap Syndromes Between Amyotrophic Lateral Sclerosis and Progressive Supranuclear Palsy.}, journal = {Clinical neuroradiology}, volume = {}, number = {}, pages = {}, pmid = {40938412}, issn = {1869-1447}, abstract = {PURPOSE: When amyotrophic lateral sclerosis (ALS), a TDP-43 proteinopathy, and progressive supranuclear palsy (PSP), a tauopathy, are associated with frontotemporal dementia (ALS-FTD or PSP-FTD), clinical differentiation can be challenging. There are no established imaging biomarkers to differentiate ALS-FTD from PSP-FTD.

METHODS: We evaluated the midsagittal midbrain area (MBA) and the midbrain-to-pons-(MB/P)-ratios in T1 MPRAGE MRI of 36 PSP cases (n = 14 PSP-FTD), 77 ALS cases (n = 10 ALS-FTD), and 72 healthy controls (HC).

RESULTS: In ALS, both parameters were indistinguishable from HC. Patients with ALS-FTD had low MBA-values and MB/P-ratios not significantly different from cases of PSP. While ROC-analyses provided an excellent diagnostic accuracy of both parameters for differentiating PSP from HC (AUCMBA = 0.974) as well as PSP from ALS (AUCMBA = 0.982), midbrain morphometry provided poor diagnostic accuracy for distinguishing ALS-FTD from PSP-FTD (AUCMBA = 0,614).

CONCLUSION: The MBA and the MB/P-ratio are morphometric parameters that have proven reliable in atypical Parkinsonian syndromes. Both can distinguish between PSP and ALS in their typical clinical forms. However, they cannot differentiate between PSP-FTD and ALS-FTD.}, } @article {pmid40938039, year = {2025}, author = {Baroni, A and Moulton, C and Cristina, M and Sansone, L and Belli, M and Tasciotti, E}, title = {Nano- and Microplastics in the Brain: An Emerging Threat to Neural Health.}, journal = {Nanomaterials (Basel, Switzerland)}, volume = {15}, number = {17}, pages = {}, pmid = {40938039}, issn = {2079-4991}, support = {[Ricerca corrente]//Italian Ministry of Health/ ; }, abstract = {Nano- and microplastics (NMPs), with nanoplastics posing higher risks due to their smaller size and greater capacity for cellular and subcellular penetration, are being referred to as ubiquitous environmental neurotoxicants, due to their ability to pass through biological barriers, including the blood-brain barrier (BBB) and nasal olfactory epithelium, and to remain lodged in neural tissue. Upon uptake, such particles disturb neuronal homeostasis by multiple converging pathways, including oxidative stress, mitochondrial dysfunction, pathological protein aggregation, and chronic neuroinflammation, all closely involved with the molecular signatures of neurodegenerative disorders (Alzheimer's, Parkinson's, Amyotrophic Lateral Sclerosis-ALS). In addition to their neurotoxicity, recent findings suggest that NMPs could disturb synaptic communication and neuroplasticity, thereby compromising the brain's capacity to recover from an injury, a trauma, or neurodegeneration, thus impacting the progression of the disease, our ability to treat it and eventually the efficacy of rehabilitation approaches. Despite these findings, our understanding remains hampered by analytical issues, the scarcity of standard detection methods, and a total lack of longitudinal studies in humans. This review combines multidisciplinary evidence on brain-plastic interactions and calls for accelerated advances in our ability to monitor bioaccumulation in humans, and to integrate neurotoxicology paradigms in the assessment of this underappreciated but growing threat to brain health.}, } @article {pmid40935268, year = {2025}, author = {Bonares, M and Shapiro, J and Vijayanathan, V and Abrahao, A and Zinmanc, L and Lau, C}, title = {Goal-concordant care in people with amyotrophic lateral sclerosis receiving palliative care.}, journal = {Journal of pain and symptom management}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jpainsymman.2025.08.046}, pmid = {40935268}, issn = {1873-6513}, abstract = {CONTEXT: Although it is known where people with amyotrophic lateral sclerosis (ALS) are dying, less is known about whether they are dying where they want to.

OBJECTIVES: To determine the rate of dying in a preferred place and factors associated with doing so in people with ALS receiving clinic-based specialist palliative care.

METHODS: Retrospective cohort study of people with ALS receiving clinic-based specialist palliative care in Toronto, Canada between July 2022 and February 2024. Association between preferred and actual place of death was determined using a χ[2] test. Factors associated with dying in a preferred place were determined using a multivariable binary logistic regression analysis.

RESULTS: In 367 individuals, at time of consultation, median age was 67 years; 60.8% had a Palliative Performance Scale score between 50-60%, and 43.3% had non-invasive ventilation. Mortality rate up to February 2024 was 41.7%. 85.4% stated a preference to die at home, 8.7% in hospital, and 5.9% in a hospice facility; whereas, 54.9% died at home, 34% in hospital, and 11.1% in a hospice facility. Of those with known preferred and actual place of death, 70.1% died in a preferred place (χ[2]=36.2; p<0.001). Dying in a preferred place was associated with increasing age (OR=1.1; 95% CI=1.0-1.1) and having non-invasive ventilation (OR=2.5; 95% CI=1.0-6.2).

CONCLUSION: Younger age and not having non-invasive ventilation at the time of consultation may suggest a higher risk of goal-discordant end-of-life care and the need to engage in early future planning when these factors are identified.}, } @article {pmid40935037, year = {2025}, author = {Wang, C and Liu, L and Liu, Y and Wei, Y and Wang, M and Huang, Y and Li, K and Lu, Q}, title = {Deep eutectic solvents-assisted alkali lignin modification for pyrolytic monophenols production.}, journal = {International journal of biological macromolecules}, volume = {328}, number = {Pt 1}, pages = {147584}, doi = {10.1016/j.ijbiomac.2025.147584}, pmid = {40935037}, issn = {1879-0003}, abstract = {The efficient valorization of alkali lignin (AL) remains a significant challenge due to the multiple impurities and complex structure of AL. Lignin modification through deep eutectic solvent (DES) and subsequent fast pyrolysis offers a promising alternative for AL valorization. Thus, this study comprehensively investigated the potential of DES-pretreated ALs (DESALs) for producing pyrolytic monophenols, with particular focus on the modification process of AL during DES pretreatment, the interaction of lignin-DES, and the techno-economic feasibility of the integrated technology. Notably, under optimal experimental conditions, the ChCl/ethylene glycol (CCEG) system demonstrated the greatest potential to enhance the yields of 4-vinyl syringol (4VS) and 4-propenyl syringol (4PS) to 12.09 wt%, achieving a selectivity of 40.60 %, without using a catalyst. Moreover, multiscale simulations were performed to illustrate the enhancement effect of DESs on the production of pyrolytic monophenols. The CCEG system exhibited the lowest |HOMO-LUMO| energy gap (161.80 kcal/mol) and the highest interaction energy (-56.56 kcal/mol). The chloride ions played an integral role in forming robust hydrogen bonds between CC and EG. Further investigation indicated that the adduct and acetal structures were synthesized, and their formation pathways were subsequently modeled. Finally, the CCEG system exhibited a negligible environmental impact and high economic feasibility.}, } @article {pmid40934740, year = {2025}, author = {Omidbakhsh, S and Tankisi, H}, title = {Effect of reference electrode position on diagnostic accuracy of split hand index in ALS.}, journal = {Neurophysiologie clinique = Clinical neurophysiology}, volume = {55}, number = {5}, pages = {103101}, doi = {10.1016/j.neucli.2025.103101}, pmid = {40934740}, issn = {1769-7131}, } @article {pmid40934673, year = {2025}, author = {Misra, SR and Das, R}, title = {The imperative of careful selection and novel strategies: Comment on Mrosk et al.'s outcomes of primary chemoradiation for advanced oral cancer.}, journal = {Oral oncology}, volume = {169}, number = {}, pages = {107676}, doi = {10.1016/j.oraloncology.2025.107676}, pmid = {40934673}, issn = {1879-0593}, } @article {pmid40934454, year = {2025}, author = {Chen, Y and Sun, S and Bai, Z and Gao, N and Yu, W and Sun, X and Li, W and Zhao, Y and Yan, C and Lin, P and Liu, S}, title = {CSF Aβ, Tau, Axonal, Synaptic, Glial, Neural, and Inflammatory Biomarkers in Patients With Sporadic Amyotrophic Lateral Sclerosis.}, journal = {Neurology}, volume = {105}, number = {7}, pages = {e213914}, doi = {10.1212/WNL.0000000000213914}, pmid = {40934454}, issn = {1526-632X}, abstract = {BACKGROUND AND OBJECTIVES: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder with multifactorial pathophysiologic mechanisms, yet reliable CSF biomarkers for the diagnosis of ALS are lacking. The aim of this study was to systematically identify CSF protein alterations in patients with sporadic ALS and to develop an effective CSF protein panel to aid in ALS diagnosis.

METHODS: This observational study was conducted at Qilu Hospital, Cheeloo College of Medicine, Shandong University. Using proximity extension assay, single-molecule array, and ELISA, approximately 200 proteins involved in different pathogenic events, including axonal damage, neuronal damage, glial responses, synaptic dysfunction, β-amyloid (Aβ) pathology, tau pathology, and neuroinflammation, were measured in the CSF. Moreover, Xtreme gradient boosting and logistic regression models were applied to develop a CSF protein panel to distinguish patients with sporadic ALS from disease controls (DCs), and the diagnostic performance was verified in an independent cohort.

RESULTS: A total of 180 participants were included, comprising 109 patients with sporadic ALS (mean age 56.7 ± 11.9 years, 58.7% male), 30 DCs (56.9 ± 12.6 years, 56.7% male), and 41 healthy controls (HCs, 57.1 ± 12.4 years, 63.4% male). Compared with HCs, patients with ALS had significantly elevated CSF levels of neurofilament light chain, chitinase proteins including chitotriosidase (CHIT1), and 55 other proteins, whereas CSF Aβ40, Aβ42, and GAP43 levels were significantly lower. Moreover, we identified a 3-protein CSF panel (CHIT1, N-CDase, and PDGF-R-alpha) that effectively distinguished patients with ALS from DCs, achieving an area under the curve of 0.927 (95% CI 0.883-0.971) in the original cohort and 0.912 (95% CI 0.841-0.985) in the replication cohort.

DISCUSSION: Using a combined approach, we comprehensively investigated CSF protein alterations in a cohort of newly diagnosed patients with ALS and provided further in vivo evidence supporting the presence of mixed copathologies in patients with ALS. Moreover, we developed a 3-protein CSF biomarker panel that effectively distinguished patients with ALS from DCs and validated its performance in an independent cohort. However, considering the relatively small cohort and lack of multiple comparison adjustments, further validation in larger, multicenter studies is warranted.}, } @article {pmid40934045, year = {2025}, author = {Majzoobi, MR and Forstmeier, S}, title = {The relationship between marital reminiscence styles and psychological well-being through mediating role of marital quality.}, journal = {Frontiers in psychology}, volume = {16}, number = {}, pages = {1639240}, pmid = {40934045}, issn = {1664-1078}, abstract = {INTRODUCTION: Marital relationships are deeply shaped by the memories couples share, as reminiscence plays a pivotal role in fostering emotional connection and intimacy. Investigating how such reminiscence is related to marital quality provides valuable insights into its influence on relational dynamics. Therefore, the purpose of the present study was to examine the relationship between marital reminiscence styles (MRSs) and psychological well-being (PWB) through the mediating role of marital quality.

METHODS: This was a descriptive-correlational study. The statistical population included all married people living in Kermanshah, Iran in 2023, among whom a sample of 304 people were selected using convenience sampling method. The measures used in this study were Majzoobi and Forstmeier's (2025) marital reminiscence styles Questionnaire (MRSQ), Chonody et al.'s (2018) Relationship quality Questionnaire, and Ryff's PWB Questionnaire. Data were analyzed through Pearson's correlation coefficient and structural equations modeling (SEM) in SPSS-26 and LISREL-10 software.

RESULTS: The findings indicated that the hypothesized model had a good fit in the studied sample. MRSs were significantly associated with PWB through marital quality. As such, it was found that obsessive MRS is related negatively to marital quality, which, in turn, related positively to PWB. Moreover, narrative MRS was related positively to marital quality, which, in turn, related positively to PWB.

DISCUSSION: These results underscore the importance of fostering positive MRSs, such as narrative MRS, to enhance marital quality and PWB in marital relationships.}, } @article {pmid40933646, year = {2025}, author = {Ferguson, R and Subramanian, V}, title = {Functional variants of CFAP410 affect the DNA damage response leading to motor neuron degeneration - Implications for ALS.}, journal = {iScience}, volume = {28}, number = {9}, pages = {113338}, pmid = {40933646}, issn = {2589-0042}, abstract = {Mutations in CFAP410, a basal body protein known to be required for the formation of primary cilia, have been identified as risk modifiers in amyotrophic lateral sclerosis (ALS), a devastating late onset neurodegenerative disorder with poor prognosis. CFAP410 is also implicated in the DNA damage response and interacts with Nek1, which has been shown to be mutated in ALS. Herein, we investigated the effect of knocking in an HA epitope tag and functional mutations into the endogenous Cfap410 gene by gene editing in mouse embryonic stem cells (mESCs). We show that primary cilia in these edited mESCs, as well as in the neural progenitors and neurons differentiated from them do not exhibit any significant difference in frequency. However, ESCs, neural progenitors, and neurons with knock-in Cfap410 variants are more susceptible to DNA damage and exhibit impaired interaction with Nek1. Our findings point to DNA damage as a convergent pathway leading to ALS.}, } @article {pmid40933539, year = {2025}, author = {Aban, JL and Lucero-Prisno, DE and Ogaya, JB and Ong, CJN}, title = {Beyond Anaphylaxis: The Overlooked Forensic Complexity of COVID-19-Triggered Pseudoangioedema.}, journal = {Academic forensic pathology}, volume = {}, number = {}, pages = {19253621251374276}, pmid = {40933539}, issn = {1925-3621}, abstract = {Gray et al's investigation into angioedema-anaphylaxis deaths amidst the COVID-19 pandemic raises important forensic implications, particularly concerning differential diagnostics in postmortem settings (1). However, a critical avenue requiring deeper contextualization is the immunopathological intersection between SARS-CoV-2-induced mast cell activation and bradykinin-mediated pathways (2).}, } @article {pmid40933233, year = {2025}, author = {Kang, K and Nunes, AS and Potter, IY and Mishra, RK and Geronimo, A and Adams, JL and Isroff, C and Wang, JE and Vaziri, A and Wills, AM and Pantelyat, A}, title = {Digital speech assessments and machine learning for differentiation of neurodegenerative diseases.}, journal = {Clinical parkinsonism & related disorders}, volume = {13}, number = {}, pages = {100389}, doi = {10.1016/j.prdoa.2025.100389}, pmid = {40933233}, issn = {2590-1125}, abstract = {INTRODUCTION: Speech impairment is a prevalent symptom of neurological disorders, including Parkinson's disease (PD), Progressive Supranuclear Palsy (PSP), Huntington's disease (HD), and Amyotrophic Lateral Sclerosis (ALS), with mechanisms and severity varying across and within conditions. Scalable digital health tools and machine learning (ML) are essential for diagnosing and tracking neurodegenerative disease.

METHODS: A total of 92 individuals were included in this study (21 PSP, 21 PD, 18 HD, 15 ALS, and 16 healthy elderly controls (CTR)). The Rainbow Passage was collected on a digital device and analyzed to extract 12 speech features representing speech production. A set of Elastic Net ML models was trained on these speech features to differentiate between diagnostic classes. A specialized Support Vector Machine ML model was then developed to differentiate PSP from PD.

RESULTS: Elastic Net models achieved a balanced accuracy of 77% over 5 diagnostic classes (group-specific sensitivities of 76% for PSP, 67% for PD, 83% for HD, 73% for ALS, and 88% for CTR) and 83% over 4 diagnostic classes (group-specific sensitivities of 83% for PSP-PD, 83% for HD, 73% for ALS, and 94% for CTR). The PSP vs. PD classification model demonstrated a balanced accuracy of 85%, with sensitivity of 88% for PSP and 82% for PD. Key speech features differentiated clinical conditions, with Total Voiced Time being the strongest positive feature for combined PSP-PD. In HD, ALS, and CTR, Ratio Extra Words, Pauses per Second, and Intelligibility were the most strongly differentiating features, respectively. Articulatory Rate emerged as the most distinguishing feature between PD and PSP.

CONCLUSION: Our findings highlight the potential of digital health technology and ML in identifying and monitoring speech features in neurodegenerative diseases.}, } @article {pmid40932783, year = {2025}, author = {Strambler, MJ}, title = {Universalism is not White: Commentary on Sue et al. (2024).}, journal = {The American psychologist}, volume = {80}, number = {6}, pages = {966-967}, doi = {10.1037/amp0001489}, pmid = {40932783}, issn = {1935-990X}, abstract = {This commentary responds to Sue et al.'s (see record 2025-04512-010) claim that principles such as universalism, individualism, objectivism, and empiricism are pillars of White epistemology. Drawing on W. E. B. Du Bois's embrace of Western intellectual traditions, this commentary argues that such ideals are not inherently racialized but rather central to human flourishing. In their critique of universalism, Sue and colleagues conflated the misapplication of universalism with the intended meaning of the concept. Rather than characterizing universalism in racial terms, this commentary contends that its accurate application promotes fairness and inclusivity and aligns with civil rights and human rights movements. Defining valuable concepts like universalism through a racial lens risks alienating scholars and undermining ideas that could advance mental health and psychological research across all demographics. (PsycInfo Database Record (c) 2025 APA, all rights reserved).}, } @article {pmid40932199, year = {2025}, author = {Spittel, S and Grehl, T and Weydt, P and Kettemann, D and Fabian, R and Rödiger, A and Smesny, U and Steinbach, R and Ilse, B and Weyen, U and Petri, S and Lumi, R and Bjelica, B and Lingor, P and Grosskreutz, J and Göricke, BM and Pfeilschifter, W and Schmeja, W and Dorst, J and Mensch, A and Siebert, J and Norden, J and Bernsen, S and Subramanian, SK and Hildebrandt, B and Walter, B and Münch, C and Maier, A and Meyer, T}, title = {Dextromethorphan/quinidine (DMQ) for reducing bulbar symptoms in amyotrophic lateral sclerosis - assessment of treatment experience in a multicenter study.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {}, number = {}, pages = {1-13}, doi = {10.1080/21678421.2025.2557932}, pmid = {40932199}, issn = {2167-9223}, abstract = {BACKGROUND: In amyotrophic lateral sclerosis (ALS), dextromethorphan/quinidine (DMQ) has been reported to reduce bulbar symptoms, including dysarthria and dysphagia. However, data on patients' perceptions of DMQ treatment are limited.

METHODS: Data on DMQ treatment were collected from 1065 ALS patients treated at 13 ALS centers between 10-2015 and 06-2025. Patient-reported outcome measures (PROM) of 179 participants were remotely assessed via the "ALS App". PROM included the self-explanatory version of the ALS Functional Rating Scale (ALSFRS-R-SE), the Net Promoter Score (NPS); and Treatment Satisfaction Questionnaire for Medication (TSQM-9).

RESULTS: Mean disease duration was 29.3 months (SD 38.1). ALS progression before treatment was 0.82 points/month (ALSFRS-R). Mean DMQ treatment duration was 8.4 months (SD 10.8), including 35.2% (n = 374) of shorter (<3 months), 35.3% (n = 375) of longer (3-9 months), and 29.5% (n = 313) of very long DMQ treatment (>9 months). Patients' recommendation (n = 178) was positive (NPS: +23) with higher scores after very long DMQ treatment (NPS +37) compared to longer (NPS +15) and shorter treatment (NPS +7.5), respectively. TSQM-9 scores (n = 163) demonstrated high satisfaction for effectiveness 60.0 (SD 25.9), convenience 73.8 (SD 18.2), and global satisfaction 63.4 (SD 29.8).

INTERPRETATION: The positive perception in PROM underscores the value of DMQ as an individualized treatment option for bulbar symptoms in ALS. However, shortage of clinical data, online assessment, and selection biases are among the limitations of this study that need to be addressed in further investigations.}, } @article {pmid40931867, year = {2025}, author = {Pavey, N and Tieppo, A and Calma, AD and Hannaford, A and Grey, E and Orden, B and Ryder, J and Lee, E and Zablotska-Manos, I and Silsby, M and Menon, P and Vucic, S}, title = {Neck flexion weakness predicts respiratory dysfunction in amyotrophic lateral sclerosis.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {}, number = {}, pages = {1-7}, doi = {10.1080/21678421.2025.2557939}, pmid = {40931867}, issn = {2167-9223}, abstract = {Objective: Neck flexion (NF) weakness is a frequently observed clinical feature in amyotrophic lateral sclerosis (ALS), particularly in advanced disease. The aim of the present study was to assess whether NF weakness could be a clinical biomarker for development of respiratory dysfunction. Methods: Sixty-two ALS patients were prospectively recruited at Brain and Nerve Research Center. Neck flexion strength was assessed by the Medical Research Council (MRC) score and handheld dynamometry (HHD). Respiratory function testing was assessed by spirometry, including forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1). Site of disease onset, disease duration, and ALSFRS-R were recorded. Results: Neck flexion weakness (MRC ≤4) was evident in 27% of ALS patients. There was a significant reduction of FVC in ALS patients with weak NF (ALSNFweakness 70.0 ± 7.2%; ALSNFnormal 86.8 ± 2.4% predicted, p = 0.038). Additionally, reduction of HHD measurements was significantly correlated with FVC (R = 0.487, p < 0.001) and FEV1 (R = 0.465, p < 0.001), and was most prominent in bulbar onset ALS (FVC: R[2] = 0.673, p = 0.002). Of relevance, the presence of NF weakness (MRC ≤ 4) was a significant predictor of reduced FVC ≤50% predicted (Chi[2] = 7.68, p = 0.006), a threshold indicating need for ventilatory support. Conclusion: Neck flexion weakness, particularly when quantified by the MRC score and HHD, serves as a marker of respiratory dysfunction in ALS patients. This simple clinical assessment may herald the development of respiratory dysfunction and requirement for respiratory ventilatory support.}, } @article {pmid40931780, year = {2025}, author = {Sabirin, W and Abd Latif, SA and Ahmad, F and Zainuddin, SI and Lam, CL and Soo, CI and Sabirin, S and Chuah, KH and Shahrizaila, N and Capelle, DP}, title = {An evaluation of the ALSSQOL-SF in the Malaysian context through cognitive interviewing.}, journal = {Neurodegenerative disease management}, volume = {}, number = {}, pages = {1-8}, doi = {10.1080/17582024.2025.2558342}, pmid = {40931780}, issn = {1758-2032}, abstract = {BACKGROUND: Quality of life is an important goal of care for people living with amyotrophic lateral sclerosis (ALS) and their carers. The ALS Specific Quality of Life instrument Short Form (ALSSQOL-SF) has been translated and validated in various cultural contexts, however its utility in the Malaysian cultural context has not yet been evaluated.

METHODS: The quality of life of 21 patients with ALS was evaluated using the ALSSOL-SF in either the English version or translated to the Malay language. A cognitive interview approach was utilized and the responses were transcribed and thematically analyzed.

RESULTS: Culture and language-related factors affecting the application of the ALSSQOL-SF were identified. Interpretations of intimacy and religiosity varied and sometimes differed significantly from the constructs underlying the ALSSQOL-SF domains.

CONCLUSION: The ALSSQOL-SF captured items from the physical domain better than those from the psycho-social and spiritual domains. Cognitive interviewing showed that patients mostly could not grasp the intended meaning of the items from the psycho-social and spiritual domains despite translation into the Malay language. There are limitations in adapting the ALSSQOL-SF for use in evaluation of QOL in Malaysian ALS patients. In the local setting a better understanding is needed about how aspects such as religion, intimacy and spiritual well-being are culturally reflected and expressed.}, } @article {pmid40931498, year = {2025}, author = {Alemán-Villa, KM and Armienta-Rojas, DA and Camberos-Barraza, J and Rábago-Monzón, ÁR and Camacho-Zamora, A and Osuna-Ramos, JF and Magaña-Gómez, JA and Guadrón-Llanos, AM and Calderón-Zamora, L and Norzagaray-Valenzuela, CD and Valdez-Flores, MA and Picos-Cárdenas, VJ and De la Herrán-Arita, AK}, title = {Neuroinflammation across the spectrum of neurodegenerative diseases: mechanisms and therapeutic frontiers.}, journal = {Neuroimmunomodulation}, volume = {}, number = {}, pages = {1-33}, doi = {10.1159/000548021}, pmid = {40931498}, issn = {1423-0216}, abstract = {Neuroinflammation has emerged as a central and dynamic component of the pathophysiology underlying a wide range of neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease, and multiple sclerosis. Far from being a secondary consequence of neuronal damage, inflammatory processes (mediated by microglia, astrocytes, peripheral immune cells, and associated molecular mediators) actively shape disease onset, progression, and symptomatology. This review synthesizes current knowledge on the cellular and molecular mechanisms that govern neuroinflammatory responses, emphasizing both shared and disease-specific pathways. We examine how innate and adaptive immune interactions contribute to neuronal vulnerability and neurodegenerative cascades, and explore the reciprocal communication between systemic and central immune compartments. Particular attention is given to emerging therapeutic strategies aimed at modulating neuroinflammation, including immunomodulatory drugs, glial-targeted interventions, and novel delivery platforms. By integrating findings across disciplines and disease models, we outline key translational challenges and propose future directions to harness neuroinflammation as a therapeutic target in the era of precision medicine. Ultimately, a deeper understanding of neuroimmune dynamics holds promise for redefining both the diagnosis and treatment of neurodegenerative disorders.}, } @article {pmid40931339, year = {2025}, author = {Epplen, ASC and Rothöft, M and Stahlke, S and Theiss, C and Matschke, V}, title = {Caffeine mitigates ROS accumulation and attenuates motor neuron degeneration in the wobbler mouse model of amyotrophic lateral sclerosis.}, journal = {Cell communication and signaling : CCS}, volume = {23}, number = {1}, pages = {394}, pmid = {40931339}, issn = {1478-811X}, mesh = {Animals ; *Caffeine/pharmacology/therapeutic use ; *Amyotrophic Lateral Sclerosis/pathology/drug therapy/metabolism ; *Motor Neurons/drug effects/pathology/metabolism ; Disease Models, Animal ; *Reactive Oxygen Species/metabolism ; Mice ; Oxidative Stress/drug effects ; Male ; *Neuroprotective Agents/pharmacology ; *Nerve Degeneration/pathology/drug therapy ; NAD/metabolism ; Humans ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by oxidative stress and progressive motor neuron degeneration. This study evaluates the potential neuroprotective effects of caffeine in the Wobbler mouse, an established model of ALS.

METHODS: Wobbler mice received caffeine supplementation (60 mg/kg/day) via drinking water, and key parameters, including muscle strength, NAD metabolism, oxidative stress, and motor neuron morphology, were assessed at critical disease stages.

RESULTS: Caffeine delayed motor performance decline, as observed in grip strength tests during the early symptomatic phase. Histological analyses revealed that significantly fewer motor neurons were lost in caffeine-treated mice at p41, despite no changes in soma morphology. Biochemical assays demonstrated that caffeine significantly reduced ROS levels and restored NAD levels to wildtype-like values, although NMNAT2 protein expression remained unaffected. The data suggest that caffeine mitigates oxidative stress through alternative pathways, potentially involving enhanced mitochondrial function and antioxidative defenses.

CONCLUSIONS: These findings highlight the potential of caffeine as a protective agent for delaying motor neuron degeneration in ALS. Future studies should explore optimal dosing strategies, combinatorial treatment approaches, and the underlying molecular mechanisms, to enable translation of these findings to human ALS patients.}, } @article {pmid40931262, year = {2025}, author = {Bonan, L and D'Angeli, D and Vacchiano, V and Postiglione, E and Incensi, A and Valentino, ML and Capellari, S and Donadio, V and Rizzo, G and Liguori, R}, title = {In-vivo evidence of synucleinopathy in parkinsonism due to VCP mutation.}, journal = {Journal of neural transmission (Vienna, Austria : 1996)}, volume = {}, number = {}, pages = {}, pmid = {40931262}, issn = {1435-1463}, abstract = {Multisystem proteinopathy 1 (MSP1) is a rare autosomal dominant disorder caused by mutations in the valosin-containing protein (VCP) gene typically presenting with inclusion body myopathy (IBM), Paget's disease of bone (PDB), frontotemporal dementia (FTD), and amyotrophic lateral sclerosis (ALS). Parkinsonism is a rare feature of MSP1, occurring in 3-4% of cases, with limited post-mortem evidence suggesting neuronal synucleinopathy. We report a case of VCP-related parkinsonism providing the first in vivo demonstration of phosphorylated alpha-synuclein deposition in skin biopsy, a highly sensitive and specific in vivo biomarker of synucleinopathy. A focused literature review on VCP-related parkinsonism is also presented to contextualize our findings. A 76-year-old man presented with akinetic-rigid parkinsonism, myopathy, pyramidal signs, and PDB. Genetic testing identified a pathogenic VCP mutation (c.277 C > T; p.R93C). Diagnostic workup included neuroimaging, electromyography, muscle biopsy, neuropsychological assessment, bone scintigraphy, and skin biopsy, which revealed abnormal intraneural phosphorylated α-synuclein deposits. Current evidence suggests that VCP mutations may promote alpha-synuclein aggregation in a subset of patients, leading to parkinsonism. This is the first in vivo demonstration of phosphorylated α-synuclein in a MSP1 patient, reinforcing the association between VCP mutations and synucleinopathy.}, } @article {pmid40930972, year = {2025}, author = {Narita, ZC}, title = {Concerns Regarding Masataka et al.'s "Revisiting the Gateway Drug Hypothesis for Cannabis: A Secondary Analysis of a Nationwide Survey Among Community Users in Japan".}, journal = {Neuropsychopharmacology reports}, volume = {45}, number = {3}, pages = {e70057}, doi = {10.1002/npr2.70057}, pmid = {40930972}, issn = {2574-173X}, mesh = {Humans ; Japan/epidemiology ; *Cannabis ; *Marijuana Use/epidemiology ; *Illicit Drugs ; Surveys and Questionnaires ; *Marijuana Abuse/epidemiology ; }, abstract = {Masataka et al.'s cannabis gateway study misrepresents the 43.8% probability of cannabis users transitioning to illegal drugs as "rare," and misuses regression via the Table 2 Fallacy. These critical issues discredit their conclusion.}, } @article {pmid40930692, year = {2025}, author = {Wei, Y and Miao, H and Najafi, H and Kim, WJ}, title = {Precise measurement of motor neuron dysfunction in Drosophila ALS model via climbing assay and leg imaging.}, journal = {Methods in cell biology}, volume = {197}, number = {}, pages = {127-148}, doi = {10.1016/bs.mcb.2025.02.008}, pmid = {40930692}, issn = {0091-679X}, mesh = {Animals ; *Amyotrophic Lateral Sclerosis/pathology/physiopathology ; Disease Models, Animal ; *Motor Neurons/pathology/metabolism ; *Drosophila melanogaster/physiology ; *Optical Imaging/methods ; Humans ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a severe neurodegenerative disorder characterized by progressive degeneration of motor neurons, leading to muscle weakness, paralysis, and death. While there is a plethora of studies focusing on many aspects of ALS, the pathogenesis of this disease is not well understood, and effective treatments are scarce. Drosophila melanogaster is a powerful model organism for studying ALS due to its genetic tractability and its evolutionarily conserved cellular and molecular processes which are also shared between the fly and human. Here, we introduce two simple and cost-effective methodologies for assessing motor neuron dysfunction in Drosophila: (1) Fast Inexpensive Climbing Test (FICT), and (2) Economical Leg Fluorescence Imaging (ELFI). These methods are established based on using basic equipment and straightforward procedures, making them accessible and applicable in various research and educational settings. FICT provides a non-invasive and high-throughput measure of motor dysfunction, while ELFI allows for direct visualization of fluorescently labeled cells in the Drosophila leg, facilitating the study of cell-cell communications in vivo. Our approach emphasizes the importance of both neuronal and glial contributions to ALS pathogenesis, offering valuable insights for the development of novel therapeutic strategies. These methods democratize access to ALS research tools, promoting global scientific collaboration and advancing our understanding of this devastating disease.}, } @article {pmid40930530, year = {2025}, author = {Geng, Y and Liu, C and Miao, H and Suen, MC and Xie, Y and Zhang, B and Han, W and Wu, C and Ren, H and Chen, X and Tai, HC and Wang, Z and Zhu, G and Cai, Q}, title = {Crystal structures of distinct parallel and antiparallel DNA G-quadruplexes reveal structural polymorphism in C9orf72 G4C2 repeats.}, journal = {Nucleic acids research}, volume = {53}, number = {17}, pages = {}, doi = {10.1093/nar/gkaf879}, pmid = {40930530}, issn = {1362-4962}, support = {32301023//Natural Scientific Foundation of China/ ; 32071188//Natural Scientific Foundation of China/ ; 32471312//Natural Scientific Foundation of China/ ; 3502Z202373009//Natural Scientific Foundation of Xiamen/ ; 16101120//Hong Kong Special Administrative Region, China/ ; 161011121//Hong Kong Special Administrative Region, China/ ; AoE/M-403-16//Hong Kong Special Administrative Region, China/ ; AoE/M-401/20//Hong Kong Special Administrative Region, China/ ; //Hong Kong University of Science and Technology/ ; 3502Z20214001//Project of Xiamen Cell Therapy Research, China/ ; }, mesh = {*G-Quadruplexes ; *C9orf72 Protein/genetics/chemistry ; Humans ; Crystallography, X-Ray ; *DNA Repeat Expansion ; Models, Molecular ; Amyotrophic Lateral Sclerosis/genetics ; Frontotemporal Dementia/genetics ; *DNA/chemistry/genetics ; Polymorphism, Genetic ; Nucleic Acid Conformation ; }, abstract = {The abnormal expansion of GGGGCC (G4C2) repeats in the noncoding region of the C9orf72 gene is a major genetic cause of two devastating neurodegenerative disorders, amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). These G4C2 repeats are known to form G-quadruplex (G4) structures, which are hypothesized to contribute to disease pathogenesis. Here, we demonstrated that four DNA G4C2 repeats can fold into two structurally distinct G4 conformations: a parallel and an antiparallel topology. The high-resolution crystal structure of the parallel G4 reveals an eight-layered dimeric assembly, formed by two identical monomeric units. Each unit contains four stacked G-tetrads connected by three propeller CC loops and is stabilized through 5'-to-5' π-π interactions and coordination with a central K+ ion. Notably, the 3'-ending cytosines form a C·C+·C·C+ quadruple base pair stacking onto the adjacent G-tetrad layer. In contrast, the antiparallel G4 adopts a four-layered monomeric structure with three edgewise loops, where the C6 and C18 bases engage in stacking interaction with neighboring G-tetrad via a K+ ion. These structurally distinct G-quadruplexes provide mechanistic insights into C9orf72-associated neurodegeneration and offer potential targets for the development of structure-based therapeutic strategies for ALS and FTD.}, } @article {pmid40930472, year = {2025}, author = {Roger, AL and Huston, ML and Spaulding, M and Metz, CM and Froeb, R and Wu, R and Kehoe, S and Mitchell, GS and ElMallah, MK}, title = {Therapeutic Acute Intermittent Hypoxia Modestly Improves Breathing in Pompe Disease.}, journal = {Respiratory physiology & neurobiology}, volume = {}, number = {}, pages = {104489}, doi = {10.1016/j.resp.2025.104489}, pmid = {40930472}, issn = {1878-1519}, abstract = {Pompe disease is an autosomal recessive neuromuscular disorder characterized by a deficiency of acid α-glucosidase (GAA), an enzyme responsible for lysosomal glycogen degradation in all cells. Respiratory distress is a common symptom among patients with Pompe disease resulting from weakness of primary respiratory neuromuscular units of the diaphragm and genioglossus and the motor neurons which innervate them. The only FDA approved treatment is enzyme replacement therapy (ERT) of recombinant human GAA (rhGAA) which slows the decline of motor function and extends life expectancy. However, ERT does not cross the blood-brain barrier and thus, is unable to treat the critical pathology present in motor neurons hindering long-term efficacy. In the present study, we sought to explore an alternative treatment for Pompe patients to improve breathing by improving the function of motor neurons. Therapeutic acute intermittent hypoxia (tAIH) is a non-invasive therapeutic modality which has had success in improving respiratory and non-respiratory motor function in patients with spinal cord injury, amyotrophic lateral sclerosis, multiple sclerosis, and stroke. Here, we treated adult Gaa[-/-] mice with a single, week-long tAIH protocol, followed by bi-weekly tAIH for 4 months. We report three critical findings: (1) both short and long-term tAIH therapy modestly improve breathing in Gaa[-/-] mice; (2) long-term tAIH-therapy in WT mice moderately elevates breathing responses; and (3) these trending improvements to respiration in Gaa[-/-] may be related to changes in chemoreflex activation, reduced kyphosis, and improved overlap of acetylcholine receptors and phrenic motor neuron axon terminals in the diaphragm muscle.}, } @article {pmid40928612, year = {2025}, author = {Farhana, S}, title = {Implementation of standardized HRQoL measurement for Chinese ischemic stroke patients: comments on Wang et al.'s longitudinal multi‑center study.}, journal = {Quality of life research : an international journal of quality of life aspects of treatment, care and rehabilitation}, volume = {}, number = {}, pages = {}, doi = {10.1007/s11136-025-04059-x}, pmid = {40928612}, issn = {1573-2649}, } @article {pmid40928564, year = {2025}, author = {Davidow, D and Paul, L and Jones, B and Hohlfeld, A and Rasenyalo, S and Dane, K and Shill, IJ and Hendricks, S}, title = {Player-Level Tackle Training Interventions in Tackle-Collision Sports: A Systematic Scoping Review.}, journal = {Sports medicine - open}, volume = {11}, number = {1}, pages = {103}, pmid = {40928564}, issn = {2199-1170}, abstract = {BACKGROUND: In tackle-collision sports, the tackle has the highest incidence, severity, and burden of injury. Head injuries and concussions during the tackle are a major concern within tackle-collision sports. To reduce concussion and head impact risk, evaluating optimal tackle techniques to inform tackle-related prevention strategies has been recommended. The purpose of this study was to perform a systematic scoping review of player-level tackle training intervention studies in all tackle-collision sports.

METHODS: The Arksey and O'Malley's five-stage scoping review process and Levac et al.'s framework were used, along with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis extension for Scoping Reviews (PRISMA-ScR) checklist. The main inclusion criteria were that the study included an intervention aimed at improving a player's tackle abilities, and the intervention had to be delivered/implemented at the player-level in a training setting.

RESULTS: Thirteen studies were included in this review, seven studies in American Football (54%), followed by a combined cohort of rugby union and rugby league players (three studies; 23%), rugby union (two studies; 15%), and one study reported on a rugby league cohort (8%). Studies focused primarily on the tackler, with the intervention incorporating a form of instruction or feedback, delivered through video or an expert coach. Other interventions included an 8-week strength and power training programme, designing practice sessions based on baseline data, and helmetless training in American Football. All interventions demonstrated a favourable change in the outcome measured-which included tackler and ball-carrier kinematics based on motion capture video, tackler proficiency scoring, tackling task analysis, head impact frequencies by xPatch head-impact sensor technology, head impact kinematics using head-impact sensors (helmet or skin patches) and football tackle kinematics with motion capture systems or video.

CONCLUSION: This review shows that a range of studies have been undertaken focusing on player-level training interventions. The quality of studies were rated as 'good', and all studies showed improvements in outcome measures. Coaches and policy makers should ensure tackle technique is profiled alongside other player characteristics, and an evidence-based approach to improving player tackling is adopted, improving both performance and reducing injury risk.

KEY POINTS: Only 13 studies tested or implemented interventions at the player level in tackle-collision sports. The focus of the studies was primarily on the tackler, with the interventions incorporating a form of instruction or feedback, which was delivered through video or an expert coach. Other interventions included an 8-week strength and power training programme, designing practice sessions based on baseline data, and helmetless training in American Football. All interventions demonstrated a favourable change in the outcome measure and provide coaches and policymakers with tackle training insights.

REGISTRATION: The systematic scoping review was prospectively registered with OSF (registration number: https://doi.org/10.17605/OSF.IO/V3KZC).}, } @article {pmid40928424, year = {2025}, author = {Matsubara, T and Izumi, Y and Hatanaka, Y and Takahara, M and Kondo, A and Matsukura, K and Arakawa, A and Haga, T and Miyamoto, R and Naruse, H and Morino, H and Toda, T and Murayama, S and Saito, Y}, title = {A Novel Neuropathological Subtype of Amyotrophic Lateral Sclerosis Characterised by Prominent Astroglial TDP-43 Pathology.}, journal = {Neuropathology and applied neurobiology}, volume = {51}, number = {5}, pages = {e70036}, doi = {10.1111/nan.70036}, pmid = {40928424}, issn = {1365-2990}, support = {JP21wm0425019//AMED/ ; JP24tm0524002//AMED/ ; JP22H04923//JSPS KAKENHI/ ; JP22K15740//JSPS KAKENHI/ ; JP24K18698//JSPS KAKENHI/ ; JPMH23FC1008//MHLW Research on rare and intractable diseases Program/ ; //Kato Memorial Bioscience Foundation/ ; //Yukihiko Miyata Memorial Trust for ALS Research/ ; //Medical Research Grants of Takeda Science Foundation/ ; //Integrated Research Initiative for Living Well with Dementia (IRIDE) of the Tokyo Metropolitan Institute for Geriatrics and Gerontology/ ; }, } @article {pmid40928392, year = {2025}, author = {Silva, S and Aires, D and Souza, A and Macedo, J and Melo, L and Câmara, S and Valentim, R and Lindquist, AR and Samora, G and Ribeiro, T}, title = {What is the influence of fatigue, ALSFRS-R scores, cognitive status, and pain in individuals with Amyotrophic Lateral Sclerosis? A cross-sectional study.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {}, number = {}, pages = {1-8}, doi = {10.1080/21678421.2025.2557971}, pmid = {40928392}, issn = {2167-9223}, abstract = {Introduction: Fatigue remains a poorly understood symptom in individuals with ALS, and little is known about its associtation with other symptoms, including functional impairment, cognition, and pain. Objective: To identify the levels of fatigue, pain, ALSFRS-R, and cognition of a Brazilian group of individuals with ALS, in order to verify possible influences between these symptoms and fatigue. Methods: This is a cross-sectional study conducted with individuals with ALS who were recruited intentionally, using a non-probabilistic sampling method. After agreeing to participate, they were assessed using a standardized assessment form, and data regarding fatigue level, ALSFRS-R scores, cognition, and pain were collected. Data were analyzed by categorizing fatigue (with and without fatigue) and considering sociodemographic and clinical covariates, followed by comparisons, bivariate analyses, and multiple linear regression analyses. Results: Data were collected from 72 individuals with ALS. Inferential statistics indicated differences between fatigue categories concerning ALSFRS-R scores, cognition, and pain. After multiple linear regression analyses, an association between fatigue and the dependent variables was identified. Conclusion: Fatigue is associated with lower ALSFRS-R scores, poorer cognitive status, and higher levels of pain in a Brazilian cohort of ALS. Additionally, age, sex, education, and length of illness were identified as potential factors for fatigue occurrence, observed more frequently in females than in males with the condition.}, } @article {pmid40927826, year = {2025}, author = {Oh, YS and Jung, R and Yon, DK and Kim, MS and Shin, JH and Shin, JI and Song, TJ}, title = {The Burden of Motor Neuron Diseases in the United States, 1990-2021: A Systematic Analysis of the Global Burden of Disease Study 2021.}, journal = {Muscle & nerve}, volume = {}, number = {}, pages = {}, doi = {10.1002/mus.70023}, pmid = {40927826}, issn = {1097-4598}, support = {//Ministry of Science and ICT, South Korea/ ; //Korea Health Industry Development Institute/ ; HI22C073600//Ministry of Health & Welfare, South Korea/ ; RS-2023-00262087//Ministry of Health & Welfare, South Korea/ ; //BK21 FOUR (Fostering Outstanding Universities for Research) funded by the Ministry of Education (MOE, Korea) and National Research Foundation of Korea (NRF-5199990614253, Education Research Center for 4IR-Based Health Care)./ ; //Bill and Melinda Gates Foundation/ ; //Australian National Health and Medical Research Council/ ; //Queensland Department of Health, Australia/ ; //Yonsei Fellowship/ ; IITP-2024-RS-2024-00438239//Institute for Information & Communications Technology Planning & Evaluation (IITP)/ ; TJS (RS-2022-II220621//Korean government (MSIT)/ ; //Korean Health Industry Development Institute (KHIDI)/ ; //Ministry of Education (MOE, Korea)/ ; NRF-5199990614253//National Research Foundation of Korea/ ; }, abstract = {INTRODUCTION/AIMS: There is a lack of up-to-date information on the burden of motor neuron diseases (MNDs) in the United States (US). This study aimed to estimate trends in the prevalence, incidence, mortality, and disability-adjusted life years (DALYs) for MNDs in the US from 1990 to 2021.

METHODS: We performed a secondary analysis of MNDs in the US using estimates of prevalence, incidence, and mortality obtained from analyses of the Global Burden of Disease 2021 dataset. These data were generated using DisMod-MR 2.1, a Bayesian meta-regression tool. Estimates were analyzed by age group, sex, region, and sociodemographic index (SDI).

RESULTS: In 2021, the age-standardized prevalence rate of MNDs in the US was 8.82 (95% uncertainty interval, 7.96-9.74) per 100,000, a 12.89% (3.10-23.66) increase from 1990 (7.82 per 100,000). Age-standardized MND-related DALY and mortality rates in 2021 were 41.36 (39.47-42.94) and 1.49 (1.38-1.56) per 100,000, respectively, increases of 4.14% (0.41%-7.68%) and 18.34% (13.86%-22.70%) compared to 1990. Geographic disparities were observed, with the West North Central reporting the highest DALY rates and the Middle Atlantic showing the lowest. The burden of MNDs was consistently greater in males across all metrics, with a male-to-female ratio of approximately 1.4:1. SDI was negatively correlated with age-standardized DALYs, years of life lost, and mortality rates.

DISCUSSION: The observed burden of MNDs in the US highlights the necessity for targeted public health interventions; equitable resource distribution; and further research into environmental, genetic, and sociodemographic factors that contribute to MNDs.}, } @article {pmid40926822, year = {2025}, author = {Guo, W and Dong, L and Lu, Q and Xie, M and Yang, Y and Zhang, Y and Lu, X and Yu, Q}, title = {Association Between Cannabis Use and Neuropsychiatric Disorders: A Two-sample Mendelian Randomization Study.}, journal = {Alpha psychiatry}, volume = {26}, number = {4}, pages = {46108}, pmid = {40926822}, issn = {2757-8038}, abstract = {BACKGROUND: The progressive legalization and widespread use of cannabis has led to its use as a treatment for certain neuropsychiatric disorders. Traditional epidemiological studies suggest that cannabis use has an effect on some neurocognitive aspects. However, it is unclear whether cannabis use is causally related to common neuropsychiatric disorders. The present study was conducted to illustrate the causal relationships of genetically predicted cannabis use with common neuropsychiatric disorders.

METHODS: We used a two-sample Mendelian randomization method using genome-wide association study (GWAS) summary statistics obtained from publicly available databases on lifetime cannabis use and 10 neuropsychiatric disorders, including multiple sclerosis (MS), Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), autism spectrum disorder (ASD), epilepsy, generalized epilepsy, focal epilepsy, migraine, migraine with aura, migraine without aura, schizophrenia (SCZ), anorexia nervosa (AN), attention-deficit/hyperactivity disorder (ADHD), and Parkinson's disease (PD) were studied with a two-sample Mendelian randomization method for GWAS summary statistics. The inverse variance weighted (IVW) method was used as the main analysis model.

RESULTS: Our study suggests that lifetime cannabis use is associated with an increased risk of developing PD (odds ratio (OR) = 1.782; 95% CI 1.032-3.075; p = 0.038) and an increased risk of ADHD in female participants (OR = 1.650; 95% CI 1.051-2.590; p = 0.029).

CONCLUSIONS: Cannabis intake may cause adverse effects relating to certain neuropsychiatric disorders. Therefore, special attention should be paid to the side effects of addictive drugs during clinical treatment to avoid harmful effects on the brain and neurocognition.}, } @article {pmid40925732, year = {2025}, author = {, }, title = {[Expert consensus on the diagnosis and treatment of sleep-disordered breathing related to neuromuscular diseases].}, journal = {Zhonghua jie he he hu xi za zhi = Zhonghua jiehe he huxi zazhi = Chinese journal of tuberculosis and respiratory diseases}, volume = {48}, number = {9}, pages = {815-830}, doi = {10.3760/cma.j.cn112147-20250614-00332}, pmid = {40925732}, issn = {1001-0939}, support = {82270107//National Natural Science Fundation of China/ ; }, mesh = {Humans ; *Neuromuscular Diseases/complications ; *Sleep Apnea Syndromes/diagnosis/therapy/etiology ; Consensus ; Noninvasive Ventilation ; Sleep Apnea, Obstructive/diagnosis/therapy ; China ; }, abstract = {Neuromuscular diseases are often accompanied by various types of sleep-related breathing disorders, which can exacerbate the underlying condition and are associated with a poor prognosis. Early identification is essential, and interventions such as non-invasive ventilation, oxygen therapy, and respiratory rehabilitation should be initiated promptly to mitigate disease progression and improve outcomes. Nevertheless, the rates of missed and misdiagnosed cases remain common in clinical practice. Currently, there are no standardized guidelines for the diagnosis and treatment of sleep-disordered breathing related to neuromuscular diseases in China. Therefore, based on the latest domestic and international research progress, and combined with domestic clinical diagnosis and treatment experience, the Sleep Disorder Group of Chinese Thoracic Society has brought together multidisciplinary experts to develop this expert consensus. This consensus provides a comprehensive overview of the epidemiology, clinical manifestations, diagnostic approaches, assessment strategies, and treatment of sleep-disordered breathing related to neuromuscular diseases. It formulates evidence-based recommendations to guide clinical practice, with the aim of providing standardized recommendations for their diagnosis and management.Statement 1: The neuromuscular disorders that are most frequently associated with sleep-disordered breathing include: myasthenia gravis (1A), amyotrophic lateral sclerosis (2B), post-polio syndrome (2B), myotonic dystrophy (2B), peripheral neuropathies (2C), and metabolic myopathies, among other neuromuscular conditions.Statement 2: Patients with neuromuscular disorders frequently develop multiple types of sleep-disordered breathing concurrently or sequentially, with obstructive sleep apnea (OSA) being the most prevalent manifestation. Distinct clinical manifestations of OSA are observed across different neuromuscular disease subtypes (1A).Statement 3: Neuromuscular disorders predispose to central sleep apnea (CSA), with clinical manifestations varying significantly across disease subtypes, stages of progression, and severity levels (1A).Recommendation 1: In patients with neuromuscular disorders exhibiting progressive hypercapnia or worsening hypoxemia, clinicians should investigate potential comorbid nocturnal alveolar hypoventilation and/or sleep-associated hypoxemia (1A).Recommendation 2: When sleep-disordered breathing is suspected, patients with neuromuscular disorders should be evaluated for symptoms of sleep-disordered breathing. Meanwhile, sleep monitoring, non-invasive CO2 monitoring, and related examinations should be actively performed according to the actual situation (1A). A polysomnography should be performed when there is a high clinical suspicion of sleep-disordered breathing but a negative result on a portable sleep monitor (1A).Recommendation 3: (1) Noninvasive positive pressure ventilation (NPPV) titration under polysomnography is the standard method to determine the effective treatment parameters for neuromuscular diseases with sleep-disordered breathing (1A). (2) Positive airway pressure titration in OSA patients with neuromuscular diseases should follow American Academy of Sleep Medicine (AASM) guidelines (1A). (3) For neuromuscular disorders with CSA or Cheyne-Stokes respiration, bi-level positive airway pressure (BPAP) with ST pattern is recommended (1A); When BPAP is not tolerated or accompanied by severe Cheyne-Stokes respiratory and heart failure in patients, adaptive support ventilation (ASV) should be used (2B). (4) Patients with neuromuscular disease and sleep-related alveolar hypoventilation should be treated with BPAP or variable assurance pressure support (VAPS) (1A). (5) BPAP with alternate frequency is preferred for neuromuscular disorders with "pseudo-central events" (1A).Recommendation 4: Oxygen therapy alone is not recommended for neuromuscular disease patients combined with sleep-disordered breathing (2D). Oxygen therapy with monitoring of CO2 level is recommended when non-invasive ventilation therapy cannot effectively correct hypoxemia (2C). Diaphragmatic pacing should not be routinely used in amyotrophic lateral sclerosis patients with respiratory failure (2B). Transvenous phrenic nerve stimulation is not currently applied to CSA caused by neuromuscular disorders (2D). Respiratory rehabilitation may improve respiratory muscle strength in a subset of patients with neuromuscular disorders (2B). Protiline can be used for REM-associated alveolar hypoventilation, and daytime sleepiness could be addressed with methylphenidate and modafinil (2C).Recommendation 5: Neuromuscular disease combined with sleep-disordered breathing is a chronic disease requiring patient-centered, individualized education and long-term follow-up management (1A).}, } @article {pmid40924345, year = {2025}, author = {Kutlubaev, MA and Pervushina, EV and Kiernan, MC}, title = {The nature of fatigue in amyotrophic lateral sclerosis: a systematic review and meta-analysis.}, journal = {Acta neurologica Belgica}, volume = {}, number = {}, pages = {}, pmid = {40924345}, issn = {2240-2993}, abstract = {OBJECTIVES: Patients diagnosed with amyotrophic lateral sclerosis (ALS) typically describe symptoms of fatigue. Despite this frequency, the underlying mechanisms of fatigue are poorly understood, and are likely multifactorial. To help clarify mechanisms, the present systematic review was undertaken to determine the risk factors related to fatigue in ALS.

METHODS: A systematic review was conducted using PubMed and Google Scholar databases using key words. From a total of 40,014 articles, 18 articles were included in the final review, following PRISMA guidelines. Meta-regression and subgroup analyses were conducted to study the relationship between fatigue in ALS and different covariates.

RESULTS: Eighteen studies were included in the analysis. A number of factors were investigated, including age, sex, disease severity and duration, site of disease onset, neurophysiological parameters, and respiratory symptoms, depression and anxiety, sleep disorders, and pain. Combined analyses established that participants with ALS who reported fatigue had more severe disease, as confirmed by lower functional rating scores, than those who did not report fatigue. The remaining factors including depression, anxiety and pain, were not found to be related to the onset of fatigue in ALS. Overall, fatigue worsened quality of life in patients diagnosed with ALS.

DISCUSSION: Fatigue in ALS appears to be particularly associated with progressive neurological deficit and disability, linked to both central and peripheral neuromuscular mechanisms.}, } @article {pmid40923926, year = {2025}, author = {Arnold, L and Tomsitz, D and Buchillon, R and Leding, J and Senner, S and Frey, S and Janjic, N and French, LE and Heinzerling, L}, title = {Successful treatment of localized Merkel cell carcinoma with avelumab in a patient with amyotrophic lateral sclerosis.}, journal = {Immunotherapy}, volume = {}, number = {}, pages = {1-4}, doi = {10.1080/1750743X.2025.2554566}, pmid = {40923926}, issn = {1750-7448}, abstract = {Currently, the first-line treatment of non-metastatic Merkel cell carcinoma (MCC) is complete resection. In case of unresectable or metastatic MCC, immune checkpoint inhibitor (ICI) therapy with avelumab (or in the US also pembrolizumab or retifanlimab) is indicated. We report on a patient with a primary, non-metastatic MCC on the left eyelid and amyotrophic lateral sclerosis (ALS). Due to ALS, the patient's communication was limited to eye movement and blinking. Complete resection or definitive radiotherapy of the tumor while preserving the function of the eye muscles was not possible. No prior data was available for patients with ALS under ICI therapy. In agreement with the patient and his family, a monotherapy with avelumab, a programmed death ligand 1 (PD-L1) inhibitor, was initiated. This led to a complete remission of the tumor with a progression-free survival of over 24 months and importantly no deterioration of the ALS.}, } @article {pmid40923569, year = {2025}, author = {Stikvoort García, DJL and Goedee, HS and van den Berg, LH and Sleutjes, BTHM}, title = {Nerve Excitability in Asymptomatic Carriers and Amyotrophic Lateral Sclerosis Patients With C9orf72.}, journal = {Annals of clinical and translational neurology}, volume = {}, number = {}, pages = {}, doi = {10.1002/acn3.70187}, pmid = {40923569}, issn = {2328-9503}, support = {//Stichting ALS Nederland/ ; }, abstract = {OBJECTIVE: We investigated the effects of C9orf72 mutation carriership on peripheral nerve excitability in asymptomatic individuals from families with a history of C9orf72 amyotrophic lateral sclerosis (ALS) and patients.

METHODS: We included 47 asymptomatic individuals from families with a history of C9orf72 ALS, of whom 23 were carriers (C9[+]) and 24 were noncarriers (C9[-]). In addition, 11 C9[+] and 110 C9[-] ALS patients and 50 healthy controls participated. Nerve excitability tests were conducted on the median nerve. We obtained standard excitability measurements as well as composites of these measurements that reflect various passive and active membrane properties. Data of C9[+] and C9[-] asymptomatic individuals were compared, followed by a kinship-adjusted comparison in asymptomatic individuals from the same families. We then compared C9[+] to C9[-] ALS patients.

RESULTS: In the subset of asymptomatic individuals from the same families, C9[+] individuals had lower values than C9[-] individuals on one of the composite excitability measurements (t = -2.15, p = 0.034), corresponding to a hypoexcitable profile consistent with smaller Na[+]-window currents. C9[+] ALS patients had a hyperexcitable profile with larger refractoriness at 2 ms and relative refractory periods than C9[-] ALS patients (t = 4.58, p < 0.001; t = 3.43, p = 0.002, respectively), which is in line with slower recovery of the Na[+]-channels from inactivation.

INTERPRETATION: Asymptomatic individuals and ALS patients carrying the C9orf72 mutation exhibit a unique electrophysiological phenotype, implicating altered Na[+]-channel characteristics compared to asymptomatic noncarriers and sporadic ALS patients. Monitoring hypoexcitable to hyperexcitable profile transitions in individuals carrying the C9orf72 mutation may be valuable as an early indicator of phenoconversion.}, } @article {pmid40922888, year = {2025}, author = {Kademani, A and Avraam, C and Montenegro, D and Paloh, A and Somannagari, N and Gupta, A and Lafi, AW and Algaba, AE and Islam, R and Fahima, C and Siddiqui, HF}, title = {Exploring the Emerging Role of Stem Cell Therapy in Neurodegenerative Diseases and Spinal Cord Injury: A Narrative Review.}, journal = {Cureus}, volume = {17}, number = {8}, pages = {e89629}, pmid = {40922888}, issn = {2168-8184}, abstract = {Neurodegenerative diseases and spinal cord injuries (SCI) pose a significant burden on the healthcare system globally. Diseases such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease precipitate cognitive, motor, and behavioral deficits. Parallelly, spinal cord injuries produce sensory and motor deficits, which are burdensome psychologically, socially, and economically. Current management strategies focus only on symptomatic relief, with no definitive cure. Stem cells have been explored for regenerative therapy. This review focuses on developments, limitations, and future potential of stem cell therapy. Stem cells affect the central nervous system via neuroprotective mechanisms, immunomodulatory effects, and mitigation of oxidative stress. The clinical implications of stem cell therapy in treating neurodegenerative diseases and SCI are debatable due to varied outcomes. Challenges related to sample size, long-term follow-up, and assessment of adverse effects should be mitigated in future research. Researchers are currently exploring optimal stem cell types along with various transplantation strategies. Biomaterials integrated with stem cells are a novel approach for treating neurodegenerative diseases and spinal cord injuries. Certain genetic modifications have shown improved results. Screening patients to ascertain better responses to therapy has proven to be a challenge. Other complications include graft vs. host reaction and degeneration of transplanted neurons due to pathogenesis and tumorigenesis. However, the majority of the potential stem cell therapeutic avenues are in the preclinical stage and are being tested on animal models. Guidelines pertaining to ethical concerns and regulatory frameworks need to be established to unfold the full potential of stem cell therapy in the clinical setting. Recent advances also show an increased need to formulate patient-specific approaches to treatment, ranging from stem cell selection to the technique of transplantation. Ongoing clinical trials can address the current challenges and leverage emerging technologies, leading to definitive treatments for neurodegenerative diseases and spinal cord injuries.}, } @article {pmid40922457, year = {2025}, author = {Eroglu, E and Harmanci, N}, title = {Emerging Molecular Targets in Neurodegenerative Disorders: New Avenues for Therapeutic Intervention.}, journal = {Basic & clinical pharmacology & toxicology}, volume = {137}, number = {4}, pages = {e70107}, doi = {10.1111/bcpt.70107}, pmid = {40922457}, issn = {1742-7843}, mesh = {Humans ; *Neurodegenerative Diseases/drug therapy/physiopathology/metabolism/genetics ; Animals ; *Molecular Targeted Therapy ; Autophagy/drug effects ; Drug Development ; }, abstract = {Neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis and frontotemporal dementia represent a significant global health burden with limited therapeutic options. Current treatments are primarily symptomatic and fail to modify disease progression, emphasizing the urgent need for novel, mechanism-based interventions. Recent advances in molecular neuroscience have identified several non-classical pathogenic pathways, including neuroinflammation, mitochondrial dysfunction, impaired autophagy and proteostasis, synaptic degeneration and non-coding RNA dysregulation. In this focused review, we highlight emerging molecular targets such as TREM2, NLRP3, mTOR, TFEB, PINK1 and SIRT3, which offer promising avenues for therapeutic intervention. We also address challenges in target validation and translational drug development, while proposing future research directions that may facilitate the design of more effective treatments. A deeper understanding of these molecular mechanisms is essential for developing disease-modifying strategies to combat neurodegeneration.}, } @article {pmid40920400, year = {2025}, author = {Urso, D and Giannoni-Luza, S and Brayne, C and Ray, N and Logroscino, G}, title = {Incidence and Prevalence of Frontotemporal Dementia: A Systematic Review and Meta-Analysis.}, journal = {JAMA neurology}, volume = {}, number = {}, pages = {}, pmid = {40920400}, issn = {2168-6157}, abstract = {IMPORTANCE: Comprehensive incidence and prevalence rates of frontotemporal dementia are currently not available.

OBJECTIVE: To estimate the incidence and prevalence of frontotemporal dementia and its clinical variants in the overall population and age subgroups.

We systematically searched PubMed, EMBASE, and Scopus between January 1, 1990, and October 22, 2024, for population-based studies estimating the incidence and/or prevalence of FTD.

DATA EXTRACTION AND SYNTHESIS: Studies and data were screened and extracted independently by 2 investigators in accordance with PRISMA guidelines. Incident and prevalent cases together with the population at risk were pooled using random-effects meta-analysis. Differences in heterogeneity by FTD variants and populations at risk were estimated.

MAIN OUTCOMES AND MEASURES: Prevalent and incident cases as numerator were based on well-defined clinical criteria. Denominators were derived either from census population data or from author-defined populations at risk.

RESULTS: From 1854 screened articles, 32 eligible population-based studies were identified. Sixteen were on prevalence and 22 on incidence reporting FTD measures, including those with estimates for the whole population and for specific age subgroups. Pooled crude incidence for FTD was 2.28 (95% CI, 1.55-3.36) per 100 000 person-years and prevalence, 9.17 (95% CI, 3.59-23.42) per 100 000 people. The behavioral-variant FTD pooled crude incidence was 1.20 (95% CI, 0.67-2.16) per 100 000 person-years and prevalence, 9.74 (95% CI, 2.90-32.73) per 100 000 people. The primary progressive aphasia variant pooled crude incidence was 0.52 (95% CI, 0.35-0.79) per 100 000 person-years and prevalence, 3.67 (95% CI, 3.05-4.43). FTD incidence among individuals younger than 65 years was 1.84 (95% CI, 0.79-4.30) per 100 000 person-years and prevalence, 7.47 (95% CI, 4.13-13.49) per 100 000 people. The denominator based on census data showed less heterogeneity than the population at risk defined by the authors (I2: for incidence, 91.6% vs 97.6%, respectively, and for prevalence, 98.8% vs 99.2%, respectively).

CONCLUSIONS AND RELEVANCE: In this systematic review and meta-analysis, estimates indicate that FTD is comparable in frequency to dementia with Lewy bodies and occurs at higher rates than progressive supranuclear palsy, corticobasal syndrome, and amyotrophic lateral sclerosis. These results provide a foundation for future research and public health strategy, especially for underrepresented populations, to better comprehend the global burden of FTD. Our findings provide robust pooled estimates of the incidence and prevalence of FTD and its subtypes, offering a foundation for future research and public health planning.}, } @article {pmid40920272, year = {2025}, author = {Ku, JB and Pak, RJ and Ku, SS and Holland, RD and Kim, HS}, title = {Clinical Efficacy of Stem Cell Therapy in Neurotraumatic and Neurodegenerative Conditions: A Comparative Review.}, journal = {Tissue engineering and regenerative medicine}, volume = {}, number = {}, pages = {}, pmid = {40920272}, issn = {2212-5469}, abstract = {BACKGROUND: Neurotraumatic conditions, such as spinal cord injury, brain injury, and neurodegenerative conditions, such as amyotrophic lateral sclerosis, pose a challenge to the field of rehabilitation for its complexity and nuances in management. For decades, the use of cell therapy in treatment of neurorehabilitation conditions have been explored to complement the current, mainstay treatment options; however, a consensus for standardization of the cell therapy and its efficacy has not been reached in the medical community. This study aims to provide a comparative review on the very topic of cell therapy use in neurorehabilitation conditions in an attempt to bridge the gap in knowledge.

METHODS: Studies were searched from the PubMed database published from 2014 to 2024 employing the terms including but not exclusive to "spinal cord injury," "brain injury," "amyotrophic lateral sclerosis," "regenerative medicine," "cell therapy," and "stem cell." Following the PRISMA 2020 statement, the studies were screened, included, and excluded. Thirty three studies were identified and selected for this review.

RESULTS: Countless researchers investigated the efficacy of various stem cell products for the treatment of numerous neurotraumatic conditions, such as spinal cord injury, traumatic brain injury, and neurodegenerative conditions such as amyotrophic lateral sclerosis. The recent decade of studies suggest that in neurotraumatic conditions, bone-marrow-derived and neural stem cells can be effective, and in neurodegenerative conditions, such as ALS, mesenchymal and neural stem cells can be efficacious.

CONCLUSION: Emerging data from the latest research is encouraging to the patients suffering from neurotraumatic and neurodegenerative conditions, which present themselves as a need for further studies with improved standardization in study design, including cell source specification, differentiation and culture method, and outcome measures to ensure a wide applicability.}, } @article {pmid40919318, year = {2025}, author = {Harrison, D and Billinton, A and Bock, MG and Clarke, NP and Digby, Z and Gabel, CA and Lindsay, N and Reader, V and Scanlon, J and Smolak, P and Thornton, P and Wescott, H and Watt, AP}, title = {Profile of NT-0527, a brain penetrant NLRP3 Inflammasome inhibitor suitable as an in vivo tool compound for neuroinflammatory disorders.}, journal = {RSC medicinal chemistry}, volume = {}, number = {}, pages = {}, pmid = {40919318}, issn = {2632-8682}, abstract = {Inhibition of the NLRP3 inflammasome has emerged as a high potential treatment paradigm for the treatment of neuroinflammation, with demonstrated anti-neuroinflammatory effects in Parkinson's disease patients and a strong rationale in Alzheimer's disease and amyotrophic lateral sclerosis. To facilitate further progress in this field, brain penetrant NLRP3 inflammasome inhibitors as leads and tool compounds are required. We discovered a small molecule NLRP3 inflammasome inhibitor, NT-0527 (11), and extensively profiled this to reveal a highly potent, selective and brain penetrant compound. This was shown to be orally bioavailable, efficacious in an in vivo model of inflammation, and with good developability characteristics. However, NT-0527 exhibited CYP 2C19 time-dependent inhibition, which halted development, but this molecule could be employed as a valuable tool compound for the investigation of neuroinflammatory conditions where NLRP3 inflammasome activation is implicated.}, } @article {pmid40917547, year = {2025}, author = {Tai, XY and Toniolo, S and Llewellyn, DJ and van Duijn, CM and Husain, M and Manohar, SG}, title = {Detection of cognitive deficits years prior to clinical diagnosis across neurological conditions.}, journal = {Brain communications}, volume = {7}, number = {5}, pages = {fcaf307}, pmid = {40917547}, issn = {2632-1297}, abstract = {Understanding the cognitive trajectory of a neurological disease can provide important insight on underlying mechanisms and disease progression. Cognitive impairment is now well established as beginning many years before the diagnosis of Alzheimer's disease, but pre-diagnostic profiles are unclear for other neurological conditions that may be associated with cognitive impairment. We analysed data from the prospective UK Biobank cohort with study baseline assessment performed between 2006 and 2010 and participants followed until 2021. We examined data from 497 252 participants, aged between 38 and 72 years at baseline, with an imaging sub-sample of 42 468 participants. Using time-to-diagnosis and time-from-diagnosis data in relation to time of assessment, we compared a continuous measure of executive function and magnetic resonance imaging brain measures of total grey matter (GM) and hippocampal volume in individuals with ischaemic stroke, focal epilepsy, Parkinson's disease, multiple sclerosis, motor neurone disease (amyotrophic lateral sclerosis) and migraine. Of the 497 252 participants [226 206 (45.5%) men, mean (SD) age, 57.5(8.1) years], 12 755 had ischaemic stroke, 6758 had a diagnosis of focal epilepsy, 3315 had Parkinson's disease, 2315 had multiple sclerosis, 559 had motor neurone disease and 18 254 had migraine either at study baseline or diagnosed during the follow-up period. Apart from motor neurone disease, all conditions had lower pre-diagnosis executive function compared to controls (assessment performed median 7.4 years before diagnosis). At a group level, focal epilepsy and multiple sclerosis showed a gradual worsening in executive function up to 15 years prior to diagnosis, while ischaemic stroke was characterised by a modest decline for a few years followed by a substantial reduction at the time of diagnosis. By contrast, participants with migraine showed a mild reduction in pre-diagnosis cognition compared to controls which improved following clinical diagnosis. Pre-diagnosis MRI GM volume was lower than controls for stroke, Parkinson's disease and multiple sclerosis (scans performed median 1.7 years before diagnosis), while other conditions had lower volumes post-diagnosis. These cognitive trajectory models reveal disease-specific temporal patterns at a group level, including a long cognitive prodrome associated with focal epilepsy and multiple sclerosis. The findings may help to prioritise risk management of individual diseases and inform clinical decision-making.}, } @article {pmid40917070, year = {2025}, author = {Xie, J and Xu, J and Tian, Z and Liang, J and Tang, H}, title = {Extended Insights Into Advancing Multi-Omics and Prognostic Methods for Cancer Prognosis Forecasting.}, journal = {Frontiers in bioscience (Landmark edition)}, volume = {30}, number = {8}, pages = {44091}, doi = {10.31083/FBL44091}, pmid = {40917070}, issn = {2768-6698}, mesh = {Humans ; *Adenocarcinoma of Lung/genetics/pathology ; *Biomarkers, Tumor/genetics ; Gene Expression Regulation, Neoplastic ; Genomics/methods ; *Lung Neoplasms/genetics/pathology/therapy/diagnosis ; Multiomics ; Prognosis ; }, abstract = {Zhang et al.'s recent article utilizes comprehensive single-cell data to identify differences in tumor cell populations, highlighting the CKS1B+ malignant cell subcluster as a potential target for immunotherapy. It develops a prognostic and immunotherapeutic signature (PIS) based on this subcluster, demonstrating good performance in predicting lung adenocarcinoma (LUAD) prognosis. The study also validates the role of PSMB7 in LUAD progression. However, there are areas for improvement. There is a lack of clarity regarding the relationship between the CKS1B+ malignant cell subcluster and the PIS, particularly in terms of why PSMB7 was selected for functional studies. The sequencing data are retrospectively obtained from public databases and lack prospective clinical validation. It is suggested to collect LUAD patient tissues for RT-qPCR and RNA-seq analysis and seek external multi-center validations. Additionally, integrating emerging multi-omics methods is recommended to further validate the findings. Despite these limitations, the study represents progress in understanding LUAD and treatment strategies, and continuous evaluation and refinement of multi-omics and machine learning methods are expected for future research and clinical practice.}, } @article {pmid40916891, year = {2025}, author = {Ludolph, A}, title = {Progress in ALS research 2025.}, journal = {Current opinion in neurology}, volume = {38}, number = {5}, pages = {566-567}, doi = {10.1097/WCO.0000000000001410}, pmid = {40916891}, issn = {1473-6551}, } @article {pmid40916690, year = {2025}, author = {Sharma, S and Gupta, M and Sharma, S}, title = {Exploring Thiophene-Based Pharmacophores as Emerging Therapeutics for Neurodegenerative Disorders.}, journal = {Critical reviews in analytical chemistry}, volume = {}, number = {}, pages = {1-29}, doi = {10.1080/10408347.2025.2554239}, pmid = {40916690}, issn = {1547-6510}, abstract = {Neurodegenerative disorders (NDD) i.e., dementia of the Alzheimer's type, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis are a rising worldwide epidemic driven by aging populations and characterized by progressive neuronal impairment. In the face of symptomatic therapies, disease-modifying treatments are beyond reach, for many years, at least, owing to the multifactorial origin, including protein aggregation, oxidative stress, neuroinflammation, and neurotransmitter dysregulation. Here, we point out thiophene, a five-membered heterocyclic sulfur-containing scaffold, as an underinvestigated but highly versatile pharmacophore with great potential in therapeutics of NDD. Here, we provide a systematic review of thiophene derivatives identified between 2006 and 2024, highlighting that these compounds are capable of modulating the aggregation of amyloid-β, inhibiting acetylcholinesterase, alleviating oxidative stress, inhibiting the toxicity of α-synuclein, and restoring neurotransmitter homeostasis. Specific emphasis is placed on their structural malleability, blood-brain barrier penetrability, and multi-targeting, which collectively present advantages over traditional heterocyclic templates. Progress in the areas of structure-activity relationship (SAR)-motivated design, synthetic methods, molecular docking, and preclinical assessment is reviewed, leading to the establishment of lead thiophene scaffolds with micro or nanomolar-range activity. This review also provides future directions, such as the requirement of pharmacokinetic improvement, target verification, and translational research to bridge preclinical discoveries with clinical utility. This article collectively places thiophene derivatives as an innovative chemical platform for the design of next-generation drugs for neurodegenerative diseases.}, } @article {pmid40916417, year = {2025}, author = {Liu, Y and Li, J and Liu, Y}, title = {HIV-Associated Lymphomas: Updates from Pathogenesis to Treatment Strategies.}, journal = {Current HIV research}, volume = {}, number = {}, pages = {}, doi = {10.2174/011570162X367092250901062629}, pmid = {40916417}, issn = {1873-4251}, abstract = {HIV-associated lymphoma (HAL) is an aggressive malignancy directly linked to HIV infection and accounts for more than 30% of cancer-related deaths in people living with HIV (PLWH). HAL subtypes, including diffuse large B-cell lymphoma (DLBCL), Burkitt lymphoma (BL), primary effusion lymphoma (PEL), and plasmablastic lymphoma (PBL), exhibit five to ten times higher incidence rates and distinct molecular profiles compared to HIV-negative lympho-mas. Pathogenesis involves HIV-driven CD4+ T-cell depletion, chronic B-cell activation, and on-cogenic viral coinfection. First-line therapy combines antiretroviral therapy (ART) with chemo-therapy, achieving complete remission rates of 60-70% for DLBCL using R-EPOCH and 50-60% for BL with CODOX-M/IVAC. Relapsed/refractory cases show durable responses to CD19-CAR-T therapy; however, only 10% of HAL patients are enrolled in pivotal immunotherapy tri-als. Severe immunosuppression necessitates PET-CT-guided de-escalation and nanoparticle-based drug delivery systems to minimize toxicity. Emerging strategies include PD-1 inhibitors and broad-spectrum antivirals targeting HIV reservoirs, underscoring the need for precision med-icine that integrates tumor genomics and viral dynamics.}, } @article {pmid40916343, year = {2025}, author = {Wu, J and Guo, J and Wu, J and Song, J and Xu, J and Lin, Y and Huang, C and Shi, C and Li, J and Li, C and Chen, Y and Wang, W and Gao, J and Zhou, Q and Zhang, Y and Li, S and Li, XJ and Zhang, CY and Chen, X and Yan, S}, title = {In vivo self-assembled siRNAs ameliorate neurological pathology in TDP-43-associated neurodegenerative disease.}, journal = {Brain : a journal of neurology}, volume = {}, number = {}, pages = {}, doi = {10.1093/brain/awaf330}, pmid = {40916343}, issn = {1460-2156}, abstract = {Abnormal accumulation of TAR DNA-binding protein-43 (TDP-43) is a hallmark of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Small interfering RNAs (siRNAs) targeting TDP-43 offer potential therapeutic strategies for these diseases. However, efficient and safe delivery of siRNAs to the central nervous system (CNS) remains a critical challenge. Here, we present a synthetic biology-based approach that leverages endogenous small RNA processing machinery to self-assemble siRNA-encapsulating small extracellular vesicles (sEVs) and utilizes the host's natural circulatory system to transport siRNAs. Specifically, we engineered liver cells to express and package TDP-43-targeting siRNAs into rabies virus glycoprotein (RVG)-tagged sEVs, which are released into circulation and cross the blood-brain barrier to deliver siRNAs to the CNS. In a mouse model of TDP-43 pathology induced by stereotactic injection of mutant TDP-43 (M337V) virus, treatment with in vivo self-assembled TDP-43 siRNAs (IVSA-siR-TDP43) effectively reduced TDP-43 accumulation, leading to significant improvements in motor function and neuropathology. Additionally, an adeno-associated virus (AAV)-based delivery system was utilized to produce IVSA-siR-TDP43, demonstrating sustained therapeutic effects in TDP-43-associated neurodegeneration. These findings highlight a novel, effective, and minimally invasive gene therapy platform for addressing TDP-43 pathology in ALS and FTLD, offering a promising avenue for future clinical applications.}, } @article {pmid40915850, year = {2025}, author = {Zhan, Y and Cao, Z and Qi, J and Luo, Y and Hu, L and Bai, L and Pan, L}, title = {Fenoxaprop-P-ethyl resistance in Alopecurus aequalis: Involvement of GSTF13 in addition to Ile-1781-Leu mutation.}, journal = {Pesticide biochemistry and physiology}, volume = {214}, number = {}, pages = {106614}, doi = {10.1016/j.pestbp.2025.106614}, pmid = {40915850}, issn = {1095-9939}, mesh = {*Herbicides/pharmacology ; *Herbicide Resistance/genetics ; *Oxazoles/pharmacology ; *Propionates/pharmacology ; *Plant Proteins/genetics/metabolism ; *Poaceae/genetics/drug effects ; Mutation ; Acetyl-CoA Carboxylase/genetics/antagonists & inhibitors ; Acetolactate Synthase/genetics/antagonists & inhibitors ; *Glutathione Transferase/genetics/metabolism ; }, abstract = {Shortawn foxtail (Alopecurus aequalis Sobol.) is a challenging weed species to manage in wheat production systems globally. In prior research, we identified a field population of A. aequalis (Aa-R) that had developed resistance to the widely used acetolactate synthase (ALS)-inhibiting herbicide mesosulfuron-methyl. In this study, we found that the Aa-R population also exhibited significant resistance to the acetyl-CoA carboxylase (ACCase)-inhibiting herbicide fenoxaprop-P-ethyl and showed broad-spectrum resistance to other three ACCase-inhibiting herbicides, haloxyfop-P-methyl, clodinafop-propargyl, clethodim, and pinoxaden. Sequence analysis of the ACCase gene revealed the presence of a known resistance mutation (Ile-1781-Leu) in the Aa-R population. Pretreatment with the GST inhibitor 4-chloro-7-nitrobenzoxadiazole (NBD-Cl) decreased the resistance to fenoxaprop-P-ethyl in the Aa-R population. We amplified an upregulated GST gene in the Aa-R population, designated AaGSTF13. Transgenic rice calli and seedlings overexpressing AaGSTF13 exhibited resistance specifically to fenoxaprop-P-ethyl, and might enhance reactive oxygen species (ROS) scavenging capacity. Further transcriptome analyses suggested that the expressions of genes associated with ROS scavenging was upregulated in transgenic plants. Our results indicate that AaGSTF13 enhances detoxification metabolism and could potentially enhances ROS scavenging in transgenic rice, which might contribute to enhanced herbicide resistance. These findings suggest that AaGSTF13 represents a promising candidate gene for the genetic improvement of new rice varieties under herbicide stress conditions.}, } @article {pmid40915735, year = {2025}, author = {Mazivila, SJ and Soares, JX and Santos, JLM}, title = {Multi-way calibration strategies involving excitation-emission data measurements from drug-modulated fluorescence in CdTe quantum dots and AgInS2 nanocrystals.}, journal = {Analytica chimica acta}, volume = {1373}, number = {}, pages = {344547}, doi = {10.1016/j.aca.2025.344547}, pmid = {40915735}, issn = {1873-4324}, abstract = {BACKGROUND: When using semiconductor quantum dots (QDs) for single-analyte sensing, recognition is commonly achieved through interactions with capping ligands attached to the QDs surface. These ligands form an organic layer that provides stability in solution and assures selectivity by binding the target analyte via surface functional groups. However, a common analytical challenge arises in the subsequent stage of the QD-based sensing scheme. Specifically, in a system combining CdTe and AgInS2 QDs, the CdTe QD core can effectively dock sodium-2-mercaptoethane sulfonate (MES) ligands, which act as recognition elements for amlodipine. In contrast, the AgInS2 QD core, may not properly anchor d-penicillamine (PCM) ligands, which bind selectively to olmesartan. This disparity in ligand-QDs affinity may lead to inconsistent excitation-emission fluorescence matrix (EEFM) signals. Such inconsistencies arise when the contribution of the four components present in the system 'CdTe QD-MES-amlodipine & AgInS2 QD-PCM-olmesartan' deviates from low-rank subspace estimated across different excitation/emission modes.

RESULTS: Upon analyzing a fixed-dosage form sample of amlodipine and olmesartan medoxomil, we demonstrate that the complexity of the mixture signal in EEFM measurements - whether from individual or combined single-analyte QD-based sensing scheme - can be experimentally assessed by determining the low-rank subspace of the analytical signals. Specifically, we evaluated whether the number of fluorescently responsive constituents across different excitation and emission modes matches the four components present in the system 'CdTe QD-MES-amlodipine & AgInS2 QD-PCM-olmesartan' - a prerequisite for the joint calibration of both analytes. If this condition is not met the analytes must be individually calibrated. Thus, a mixture of single-analyte QD-based sensing scheme, involving different concentrations of amlodipine and olmesartan medoxomil, was used to generate a set of EEFM measurements. A rank-two model was found optimal for emission wavelengths, while a rank-three model was calculated for excitation wavelengths. These results reveal an evident rank-deficient as at least four-components are present in the QD-sensing photoluminescence modulation process.

SIGNIFICANCE: The unfolded partial least-squares (U-PLS) model was successfully applied for the determination of amlodipine-net analyte signal (NAS) from binary CdTe QDs fluorescence modulation. In contrast, the olmesartan- NAS from ternary AgInS2 QDs fluorescence modulation did not allow a combined calibration. Consequently, the analytes must be individually calibrated based on their respective individual mixture signals using either PARAllel FACtor (PARAFAC) analysis or multivariate curve resolution - alternating least-squares (MCR-ALS) model according to the data structure.}, } @article {pmid40914817, year = {2025}, author = {Alves, I and Aiello, EN and Lopes, D and Gromicho, M and Simão, S and Moreschi, A and De Luca, G and Curti, B and Silani, V and Ticozzi, N and Poletti, B and de Carvalho, M}, title = {Reliable change indices for the cognitive section of Portuguese version of the Edinburgh Cognitive and Behavioural ALS screen (ECAS).}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {}, number = {}, pages = {1-4}, doi = {10.1080/21678421.2025.2555216}, pmid = {40914817}, issn = {2167-9223}, abstract = {This study aimed to derive standardized regression-based (SRB) reliable change indices (RCIs) for the cognitive section of the Portuguese Edinburgh Cognitive and Behavioral ALS Screen (ECAS-C). Forty-nine MND patients undergoing the ECAS were followed-up (T1) at 7.2 ± 2 months (range = 5-12). RCIs were derived via an SRB approach by accounting for demographic, motor-functional and test-related variables. Practice effects were detected as to Total and Memory measures; all ECAS-C measures proved to be reliable at retest. Baseline ECAS-C measures predicted their follow-up performances. SRB RCIs herewith delivered will help assess MND patients' cognition over time, although they would benefit from further validation in independent cohorts.}, } @article {pmid40914405, year = {2025}, author = {Wang, J and Li, X and Yang, F and Guo, P and Ren, C and Duan, Z and Bi, M and Kong, Y and Zhang, Y and Lu, J}, title = {Exploration of endoplasmic reticulum stress-related gene markers in amyotrophic lateral sclerosis: a comprehensive analysis of bioinformatics and machine learning.}, journal = {Analytical biochemistry}, volume = {}, number = {}, pages = {115969}, doi = {10.1016/j.ab.2025.115969}, pmid = {40914405}, issn = {1096-0309}, abstract = {This study aimed to investigate potential biomarkers related to Endoplasmic reticulum (ER) stress in Amyotrophic lateral sclerosis (ALS) through a comprehensive bioinformatic approach. The gene expression profiles of ALS patients and healthy controls were downloaded from the Gene Expression Omnibus (GEO) database. ER stress-related genes were collected from the MSigDB databases and document literature. The "limma" R package was employed to detect the differentially expressed ER stress-related genes (DE-ERSGs). Three methods of machine learning were applied to select the hub DE-ERSGs. ROC curves were conducted to evaluate model performance. An external dataset was chosen to evaluate the diagnostic capability of hub genes. The CIBERSORT algorithm was used to evaluate the immune cell infiltration characteristics. Additionally, we constructed a systematic ceRNA regulatory network using Cytoscape software and predicted the possible drug candidates using the Enrichr platform. Molecular docking analysis was used to further validate the binding ability of the candidate drug molecules to the hub genes. Six hub DE-ERSGs (ABCA1, CKAP4, TOR1AIP1, MMP9, EDC4, and ALPP) were identified, and the related models performed well. These hub genes were concentrated in multiple pathways and related to various immune cells. Drugs such as nitroglycerin, diazepam, FENRETINIDE, and edaravone exhibited good binding affinity to the hub genes, indicating that they may be promising drugs for the management of ALS. This study revealed the essential role of ER stress in the pathogenesis of ALS from an integrative perspective, providing guidance for the development of new therapeutic targets and diagnostic strategies.}, } @article {pmid40913874, year = {2025}, author = {Peethambaran, ST and Ashokan, A and Subhose, V}, title = {A case report on Ayurvedic management of progressive bulbar palsy-A rare amyotrophic lateral sclerosis phenotype.}, journal = {Journal of Ayurveda and integrative medicine}, volume = {16}, number = {5}, pages = {101176}, doi = {10.1016/j.jaim.2025.101176}, pmid = {40913874}, issn = {0975-9476}, abstract = {This case report is the description of a devastating illness, Progressive Bulbar Palsy (PBP) of a sixty-seven years old male patient. He presented with complaints of slurred speech, hearing impairment, generalised weakness of limbs, weakened grip to hold objects in hand, difficulty to walk with normal speed, frequent dizzy feeling while walking, severe fatigue, increased anger, heaviness of head, depression, anxiety, decreased memory and headache for 1 year. When he consulted conventional medicine, in Magnetic Resonance Imaging (MRI) of brain, only 'Partial empty sella' and age related mild cerebral atrophy was detected and the patient was diagnosed PBP clinically. They prescribed Riluzole 50 mg tablet twice a day and Fluoxetine 10mg capsules at night time for 3 months, but obtained no relief for symptoms and consulted this Out Patient Department (OPD). In Ayurvedic parlance, PBP resembles conditions like Kaphavruta vata. In this patient, Pittavritavata symptoms like bhrama (∼dizziness) was also present in increased severity. Diagnosis was done with the aid of Gold Coast diagnostic criteria. Internal and external medications with properties alleviating avarana (∼occlusion) of vata by kapha and pitta, shodhana (∼expelling the aggravated doshas and cleanses the body internally), rejuvenating (Rasayana) properties, for overall strengthening of nervous system and musculoskeletal system, enhancing balance and coordination, improving speech and memory were used. The assessment was done before and after the treatment by 'Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R). The score before and after the treatment was 35 and 45 respectively out of 48. The treatment helped to increase the quality of life exceptionally as symptomatic relief was obtained. As it is a devastating disorder with poor prognosis and most probably will lead to death, it is advisable to repeat the treatments in regular intervals, depending on the recurrence of symptoms, if any.}, } @article {pmid40913365, year = {2025}, author = {Zhang, J and Kaiser, E and Marcelis, LFM and Vialet-Chabrand, S}, title = {DynG: a dynamic scaling factor for thermographic stomatal conductance estimation under changing environmental conditions.}, journal = {The New phytologist}, volume = {}, number = {}, pages = {}, doi = {10.1111/nph.70555}, pmid = {40913365}, issn = {1469-8137}, support = {202006300044//China Scholarship Council/ ; 19652//Nederlandse Organisatie voor Wetenschappelijk Onderzoek/ ; }, abstract = {Thermal imaging is a key plant phenotyping and monitoring technique but faces major bottlenecks in accurately and efficiently inferring stomatal conductance (gsw) from leaf temperature. The conductance index (Ig) was previously proposed to estimate gsw from thermography by linking temperature differences between real and artificial leaves (ALs) based on the leaf energy balance. However, Ig is highly sensitive to environmental fluctuations, hampering interpretation and reducing reproducibility. We developed a simple and novel correction factor (named DynG) for Ig that accounts for environmental fluctuations when scaling Ig to gsw. This was achieved by capturing temperature variations in a set of ALs with a range of known constant pore conductances. This approach provided the Ig-conductance relationship, using ALs as a reference, to infer gsw of real leaves from their measured Ig. In fluctuating environments, gsw estimated using DynG showed greater accuracy and stability than gsw calculated from Ig alone, and was in good agreement with gsw determined using lysimetric and gas exchange methods. DynG's power was further showcased in distinguishing gsw of Arabidopsis genotypes differing in stomatal traits (Col-0, epf1epf2, and EPF2OE). We conclude that Ig corrected with DynG can reliably estimate gsw in fluctuating environments without complex modeling, opening new avenues for gsw phenotyping and monitoring.}, } @article {pmid40912729, year = {2025}, author = {LaBarbera, V and Dai, X and Sachs, G}, title = {Co-occurrence of ipsilateral partial Horner's syndrome in a patient with monomelic amyotrophy.}, journal = {BMJ case reports}, volume = {18}, number = {9}, pages = {}, doi = {10.1136/bcr-2025-265315}, pmid = {40912729}, issn = {1757-790X}, mesh = {Humans ; *Horner Syndrome/complications/diagnosis ; *Spinal Muscular Atrophies of Childhood/complications/diagnosis ; Male ; Female ; Diagnosis, Differential ; Middle Aged ; }, abstract = {Monomelic amyotrophy (MMA) is a lower motor neuron predominant disorder affecting an upper limb, which can mimic amyotrophic lateral sclerosis (ALS). It often presents with unilateral, distal upper limb weakness and atrophy, whose trajectory is one of an initial period of progression followed by a prolonged plateau, as opposed to the typically relentless progression as is seen in ALS. This case report describes a novel observation of a patient with MMA with an unexplained ipsilateral partial Horner's syndrome (miosis and ptosis). Horner's syndrome is known to result from sympathetic dysfunction from lesions from the hypothalamus to the cervical/upper thoracic spine and can be seen with brachial plexopathies, but has never been, to our knowledge, described in MMA. This finding is of interest because it may facilitate earlier diagnosis of MMA in isolated upper extremity, lower motor neuron-predominant syndromes, as Horner's syndrome is not known to complicate ALS.}, } @article {pmid40912409, year = {2025}, author = {Bordoni, M and Scarian, E and Jacchetti, E and Viola, C and Diamanti, L and Dragoni, F and Di Gerlando, R and Rizzo, B and Raimondi, MT and Gagliardi, S and Pansarasa, O}, title = {HDAC6 and TDP-43 promote autophagy impairment in amyotrophic lateral sclerosis.}, journal = {Neurobiology of disease}, volume = {}, number = {}, pages = {107079}, doi = {10.1016/j.nbd.2025.107079}, pmid = {40912409}, issn = {1095-953X}, abstract = {TDP-43 is known to bind the mRNA of histone deacetylase 6 (HDAC6), influencing its RNA translation. Many studies suggest that HDAC6 participates in the regulation of autophagy, which we found impaired in sporadic ALS (sALS) patients. Aim of this work is to evaluate the interaction between TDP-43 and HDAC6 mRNA and to evaluate the effect of the up- and down-regulation of HDAC6 on autophagy in SH-SY5Y cells. Protein level of HDAC6 and TDP-43 binding with HDAC6 mRNA by RNA immunoprecipitation were studied on sALS peripheral blood mononuclear cells (PBMCs). Initially, we observed increased level of HDAC6 protein and increased binding of its mRNA with TDP-43 in sALS PBMCs. We observed that TDP-43 transfection and aggregation in SH-SY5Y cells leads to overexpression of HDAC6. Our results indicate that the autophagy pathway is sensitive to both extremes of α-tubulin acetylation. Indeed, a marked reduction due to HDAC6 overexpression, as well as an excessive increase following HDAC6 downregulation, both result in autophagic dysfunction. This work supports the hypothesis that dysregulation of HDAC6 is a key factor in the disruption of the autophagy pathway previously detected in sALS PBMCs. Our work suggests for the first time that TDP-43 influences autophagy by binding and modulating HDAC6 mRNA. This new pathway suggests that in ALS the aggregation of TDP-43 leads to the overexpression of HDAC6 which impairs autophagy pathway. Thus, our work suggest that in sALS HDAC6 should be tuned and these findings could be exploited in the future as possible therapeutic target.}, } @article {pmid40912321, year = {2025}, author = {Durpoix, A and Blay, M and Moog, C and Rolling, J and Weiner, L and Lalanne, L and Weibel, S}, title = {Clarifying conceptualization of emotional dysregulation: Differences with emotional lability during 4-month DBT skills training - A naturalistic study.}, journal = {Journal of affective disorders}, volume = {}, number = {}, pages = {120199}, doi = {10.1016/j.jad.2025.120199}, pmid = {40912321}, issn = {1573-2517}, abstract = {INTRODUCTION: Emotion dysregulation is common in many different psychiatric disorders and it can be effectively treated with the well-established Dialectical Behavioral Therapy (DBT). Despite its clinical relevance and increasing scientific interest, emotional dysregulation (ED) is sometimes conflated with emotional lability (EL). However, these constructs differ: ED involves top-down neurobiological processes, while EL involves bottom-up processes. As psychotherapy essentially influences top-down processes compared to pharmacotherapy, this study aimed to investigate whether ED is more sensitive to DBT than EL.

METHOD: Our naturalistic study involved the 39 participants (sex ratio = 9 m/30w, mean age = 33.23) who completed questionnaires assessing ED (DERS-36) and EL (ALS-18) before then after transdiagnostic DBT skills training (DBT-ST). The diagnoses of participants included BPD (64 %), BD (23 %), ADHD (23 %), addiction (17 %) or eating disorder (17 %). DBT was performed in a transdiagnostic group over 4 months.

RESULT: After DBT-ST, ED improved significantly with a medium effect size (d = 0.73), while EL showed no significant change (d = 0.13). The percentages of improvement on DERS were significantly higher than on ALS (p < 0.002, d = 0.50). The correlation between these both measures decreased during therapy from r = 0.37 to r = 0.32.

DISCUSSION: Our findings indicate that ED improved more than EL after DBT and that their correlation diminished during therapy. These results suggest that ED is a different process from EL and that ED is more sensitive to treatments like DBT Skills Training. To confirm these findings, further studies are needed ideally with larger sample size, long-term follow-up and a controlled design.}, } @article {pmid40912271, year = {2025}, author = {Heyne, S and Kuzmanova, A and Esser, P and Mehnert-Theuerkauf, A and Metelmann, M}, title = {[Psychosocial support needs and requirements for psychosocial care programs for caregivers of patients with ALS - A qualitative analysis from the "potentiALS" project].}, journal = {Psychotherapie, Psychosomatik, medizinische Psychologie}, volume = {}, number = {}, pages = {}, doi = {10.1055/a-2679-1065}, pmid = {40912271}, issn = {1439-1058}, abstract = {ALS is a terminal illness that places significant burden on caregivers due to the intensive care demands. Little research exists on the specific design of psychological support programs for caregivers of ALS patients. This study aims to identify psychosocial needs of caregivers, specific therapeutic topics and structural requirements for tailored support programs.The study is based on a subset of qualitative data from a participatory mixed-methods observational study. Semi-structured, one-hour interviews were conducted with caregivers of ALS patients, either online or in person. The transcripts were analyzed using Mayring's qualitative content analysis.Four caregivers participated in the study. They reported a high need for psychological support, especially immediately following the diagnosis. Key themes included emotional relief through dialogue with psychologists, strategies for emotion regulation, and fostering self-care. Practical needs highlighted the importance of clear guidelines for caregiving organization, assistance with medical devices, and the development of supportive programs to help manage life and plan for the future during challenging circumstances. Participants emphasized that support programs should be flexible, easily accessible, and personalized. Individual sessions with the option of in-person or online formats were preferred. Caregivers highlighted the necessity of continuous support throughout the disease trajectory, particularly during critical phases.The results of our study highlight the psychosocial challenges faced by caregivers of ALS patients. The findings emphasize the need for comprehensive support systems that address both the emotional and practical needs of caregivers.}, } @article {pmid40911608, year = {2025}, author = {Li, Z and Qiao, Q and Han, Z and Liu, X and Wang, Y and Tang, H and Deng, L}, title = {Terrestrial laser scanning in forestry: Accuracy and efficiency in measuring individual tree parameters.}, journal = {PloS one}, volume = {20}, number = {9}, pages = {e0331126}, doi = {10.1371/journal.pone.0331126}, pmid = {40911608}, issn = {1932-6203}, mesh = {*Trees/anatomy & histology/growth & development ; *Forestry/methods ; Forests ; *Lasers ; Populus ; }, abstract = {With the growing global emphasis on forest resource monitoring, evaluating the accuracy of retrieving key individual tree parameters-such as tree position, tree height, and diameter at breast height (DBH)-using Terrestrial Laser Scanning (TLS) has become an important research focus. TLS has been widely applied in forest surveys due to its significant advantages in data acquisition efficiency and measurement precision. However, studies on the accuracy of extracting forest parameters from single-station, single-scan TLS data remain limited, underscoring the need for systematic evaluation and validation. This paper analyzes the accuracy and effectiveness of TLS in extracting structural parameters (tree height and DBH) and its position using Poplar and Styphnolobium as examples by using TLS, Airborne laser Scanning (ALS), and combining with field measurements. Results show that tree height estimates from single-scan TLS is limited in accuracy: the RMSE of 11.61 m in the Populus plot and 2.13 m in the Styphnolobium plot. Within a 50 m radius, single-scan TLS achieves a tree detection rate of 55.96-64.26% and a DBH RMSE of 1.60 cm (RRMSE: 9.03%). In addition, the point root mean square error of individual tree measurements remains at 0.11 m. These findings highlight the potential of TLS as an effective tool for forest inventory and provide a basis for evaluating the reliability of TLS-based plot measurements.}, } @article {pmid40911406, year = {2025}, author = {Vieira, RGS and Lima, ÍNDF and Pondofe, KM and Maciel, ACMG and Dourado-Júnior, MET and Otto-Yáñez, M and Vilaró, J and Torres-Castro, R and Uribe, RV and da Fonsêca, JDM and Lo Mauro, A and Resqueti, VR and Aliverti, A and Fregonezi, GAF}, title = {Acute Effects of Mechanical Insufflation-Exsufflation on Cough Peak Flow, Chest Wall Volumes, and Breathing Pattern of Patients With Amyotrophic Lateral Sclerosis.}, journal = {Respiratory care}, volume = {}, number = {}, pages = {}, doi = {10.1177/19433654251367414}, pmid = {40911406}, issn = {1943-3654}, abstract = {Background: Mechanical insufflation-exsufflation (MI-E) consists of increasing expiratory air flow, thereby promoting an increase in cough peak flow (CPF) and secretion clearance. Respiratory impairment, characterized by reduced lung volumes and ineffective cough, is the major cause of morbidity and mortality in patients with amyotrophic lateral sclerosis (ALS). This study aimed to assess the acute effects of MI-E on CPF and chest wall compartmental and operational volumes in patients with ALS. Methods: Ten ALS subjects (6 males) were studied by optoelectronic plethysmography (OEP) to assess the immediate effects of MI-E on CPF, chest wall volume variations and their distribution in the chest wall compartments, breathing pattern, and shortening velocity of the respiratory muscles before, during, and after the application of MI-E. Results: No differences were observed in the CPF analysis between time points (pre, MI-E, post). A significant increase in CPF (P = .01) was obtained immediately after the application of MI-E in subjects with spinal-onset ALS (n = 7). No significant differences in total and compartmental lung volumes and chest wall operational volumes were observed between pre MI-E (quiet breathing), during MI-E (after coughs 1, 2, and 3), and post MI-E time points. Conclusions: The application of the MI-E technique may increase CPF in individuals with spinal ALS. However, no significant changes in total thoracic volumes, total and compartmental chest wall volumes, or changes in breathing patterns in the participants in our sample after the application of the technique were observed.}, } @article {pmid40911048, year = {2025}, author = {Massey, C and Hobson, E and McDermott, C and Griffiths, AW}, title = {Living with cough and secretion issues: the experiences of people with amyotrophic lateral sclerosis and their caregivers.}, journal = {Disability and rehabilitation}, volume = {}, number = {}, pages = {1-16}, doi = {10.1080/09638288.2025.2555973}, pmid = {40911048}, issn = {1464-5165}, abstract = {PURPOSE: To explore the experiences of people living with amyotrophic lateral sclerosis (ALS) and their caregivers managing cough and secretion problems.

METHODS: A qualitative study was completed with 15 individuals participating in 10 interviews; 10 people living with ALS and five informal caregivers. Interview methods were adapted to ensure inclusivity of participants who had physical, respiratory and communication impairments. Data was analysed inductively using reflexive thematic analysis.

RESULTS: Our analysis identified the challenges of living day to day with cough and secretion problems. Care coordination and the presence of informal caregivers were important in ensuring that cough and secretion interventions could be implemented successfully. Participants felt access to cough and secretion knowledge and skills specific to ALS was key to supporting care and supported them to acquire information which influenced decision-making around their care.

CONCLUSION: Cough and secretion care in ALS is multifaceted and multifactorial. Future development of clinical interventions in this area are needed to support the complex web of professionals, treatments and knowledge to optimise care.}, } @article {pmid40910745, year = {2025}, author = {Simoni, D and Gotkine, M and Ben-Dov, IZ and Lerner, B}, title = {Identifying diagnostic markers in the health records of prediagnostic amyotrophic lateral sclerosis patients.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {}, number = {}, pages = {1-11}, doi = {10.1080/21678421.2025.2539898}, pmid = {40910745}, issn = {2167-9223}, abstract = {Objective: Amyotrophic lateral sclerosis (ALS) has a poorly understood preclinical phase, particularly concerning diagnostic blood markers. Our objective was to determine whether distinct patterns in routinely collected clinical and laboratory markers exist during the preclinical phase and could be incorporated to facilitate early diagnosis. Methods: We conducted a longitudinal, retrospective, case-control study with health records of prediagnostic ALS patients (PDALS) from health maintenance organizations covering approximately 40% of the Israeli population. We included PDALS with at least 10 clinical visits and a minimal observation period of 36 months prior to the diagnosis date to measure differences between PDALS and controls and analyzed data from 1,810 adult individuals; 362 PDALS and 1,448 age- and sex-matched controls. Results: Significant differences were found in PDALS many months before the diagnosis date. These included biochemical parameters such as urea, creatinine, CK, calcium, iron, and liver enzymes, hematological values, and BMI. Some differences were detectable over 10 years prior to the diagnosis date. Conclusions: This study highlights the potential for early detection of ALS based on blood markers in the years preceding clinical diagnosis. These findings could significantly expedite diagnosis, identify individuals at risk for ALS, and uncover unrecognized disease mechanisms.}, } @article {pmid40910231, year = {2025}, author = {He, M and Zeng, S and Tang, Z and Qin, L and Yan, W and Wang, C and Zhang, H and Chen, Z and Long, Z}, title = {A Decade of Research on C9orf72 in Frontotemporal Dementia (2014-2024): A Bibliometric Analysis of Global Trends and Hotspots.}, journal = {Current neuropharmacology}, volume = {}, number = {}, pages = {}, doi = {10.2174/011570159X388118250808030811}, pmid = {40910231}, issn = {1875-6190}, abstract = {INTRODUCTION: Frontotemporal dementia (FTD) is the third most frequent dementia and the leading dementia subtype in individuals under 65. The discovery of C9orf72 (chromosome 9 open reading frame 72) GGGGCC abnormal expansion is a major genetic cause of both FTD and amyotrophic lateral sclerosis (ALS), linking these diseases along a clinicopathological spectrum. This study aimed to depict the research landscape of C9orf72 in FTD over the past decade, track emerging research hotspots, and provide insights into under-researched areas.

METHOD: Based on the Web of Science database, a bibliometric analysis was conducted to explore publication trends, key contributors, funding sources, journal categories, co-authorship networks, and keyword co-occurrence, clustering, and bursts.

RESULTS: A total of 1,220 articles were identified, with sustained output of over 100 articles annually. The majority of contributions and funding support came from North America and Europe. Hot research themes included hexanucleotide repeats, nucleocytoplasmic transport, disease mechanisms, and therapeutic targets.

DISCUSSION: North America and Europe were highly productive, supported by higher regional prevalence, genetic burden, and robust funding. Ploy-GR in cerebrospinal fluid has emerged as a diagnostic biomarker. Pathogenic mechanisms remain complex, involving both gain- and loss-of-function effects. Metformin and antisense oligonucleotides were considered as potential therapeutics. Further research is needed in underrepresented populations and on the translational potential of emerging molecular targets.

CONCLUSION: This study offers a comprehensive overview of current trends and future directions over the past decade in C9orf72-related FTD research, allowing researchers-particularly those new to the area-to quickly understand the current landscape.}, } @article {pmid40909873, year = {2025}, author = {Wang, X and Dong, B and Gan, Q and Li, J and Wu, P and Guan, Y and Wang, J}, title = {Unraveling the Vicious Cycle: Oxidative Stress and Neurotoxicity in Neurodegenerative Diseases.}, journal = {FASEB bioAdvances}, volume = {7}, number = {8}, pages = {e70041}, pmid = {40909873}, issn = {2573-9832}, abstract = {Oxidative stress is characterized by an imbalance between the production and elimination of free radicals, where the rate of free radical generation surpasses the rate of their removal. This imbalance can lead to tissue and organ damage, contributing to the pathogenesis of various diseases. The nervous system, due to its high oxygen consumption, is particularly susceptible to oxidative stress. Numerous neurotoxins can induce neurotoxicity through oxidative stress, thereby contributing to the onset of neurodegenerative diseases, such as Parkinson's disease, Alzheimer's disease, Huntington's disease, and amyotrophic lateral sclerosis. Furthermore, neurotoxicity can exacerbate oxidative stress by disrupting mitochondrial metabolism and impairing the activity of antioxidant enzymes, thereby intensifying neurotoxic effects. This review examines the mechanisms underlying the interaction between oxidative stress and neurotoxicity and explores strategies to mitigate neurotoxicity by reducing oxidative stress, with the aim of informing future clinical approaches for the treatment of neurodegenerative diseases.}, } @article {pmid40909834, year = {2025}, author = {Homann, J and Korologou-Linden, R and Viallon, V and Morgan, S and Dobricic, V and Deecke, L and Schessner, JP and Smith-Byrne, K and Birtles, D and Zhao, Y and Wuu, J and Artaud, F and Hajizadah, F and Huerta, JM and Ohlei, O and Lebedev, M and Kolijn, PM and Guevara, M and Jimenez-Zabala, A and Sánchez, MJ and Trobajo-Sanmartín, C and Colorado-Yohar, SM and Alonso-Martín, S and Petrova, D and Sieri, S and Berger, K and Peters, S and Wareham, N and Kaaks, R and Travis, RC and Vermeulen, RCH and , and Tzoulaki, I and Elbaz, A and Mann, M and Sacerdote, C and Masala, G and Katzke, V and Benatar, M and Bertram, L and Middleton, L and Riboli, E and Gunter, MJ and Ferrari, P and Robinson, O and Lill, CM}, title = {Redefining ALS: Large-scale proteomic profiling reveals a prolonged pre-diagnostic phase with immune, muscular, metabolic, and brain involvement.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, doi = {10.1101/2025.08.20.25334061}, pmid = {40909834}, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder with a largely unknown duration and pathophysiology of the pre-diagnostic phase, especially for the common non-monogenic form.

METHODS: We leveraged the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort with up to 30 years of follow-up to identify incident ALS cases across five European countries. Pre-diagnostic plasma samples from initially healthy participants underwent high-throughput proteomic profiling (7,285 protein markers, SomaScan). Cox proportional hazards models based on 4,567 participants (including 172 incident ALS cases) were used to identify protein biomarkers associated with future ALS diagnosis. Top results were indirectly validated in two independent case-control studies of prevalent ALS (n=417 ALS, 852 controls). Functional annotation included cross-disease comparisons, gene set and tissue enrichment testing, organ-specific proteomic clocks, and the application of large-language models (LLM).

FINDINGS: Five proteins (SECTM1, CA3, THAP4, KLHL41, SLC26A7) were identified as significant pre-diagnostic ALS biomarkers (FDR=0.05), detectable approximately two decades before diagnosis. Of these, all except SECTM1 were indirectly validated in independent cohorts of prevalent ALS cases, supporting their clinical significance. Additionally, 22 nominally significant (p<0.05) pre-diagnostic biomarkers were FDR-significant in prevalent ALS with consistent effect directions. Cross-disease comparisons with pre-diagnostic Parkinson's and Alzheimer's disease suggested a largely specific pre-diagnostic ALS biomarker signature. Gene ontology and tissue enrichment highlighted early involvement of immune, muscle, metabolic, and digestive processes. Furthermore, analyses of proteomic clocks revealed accelerated aging in brain-cognition, immune, and muscle tissues before clinical diagnosis. Druggability and LLM analyses revealed possible therapeutic targets and novel strategies, emphasizing translational relevance.

INTERPRETATION: Our study provides first evidence of ultra-early molecular changes in common ALS up to two decades prior to clinical onset, mainly affecting immune, muscle, metabolic, digestive, and cognitive systems. Our study nominates several compelling candidates for risk stratification studies and novel therapeutic targets for early intervention.

FUNDING: Clinical Research in ALS and Related Disorders for Therapeutic Development (CreATe) Consortium, Cure Alzheimer's Fund, Michael J Fox Foundation, Interdisciplinary Centre for Clinical Research, University Münster.}, } @article {pmid40909710, year = {2025}, author = {Gautier, O and Blum, JA and Nguyen, TP and Klemm, S and Yamakawa, M and Sinnott-Armstrong, N and Zeng, Y and Davis, CO and Bombosch, J and Nakayama, L and Guttenplan, KA and Chen, D and Kathira, A and Zhao, L and Rexach, JE and Greenleaf, WJ and Gitler, AD}, title = {An emergent disease-associated motor neuron state precedes cell death in a mouse model of ALS.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2025.08.21.671404}, pmid = {40909710}, issn = {2692-8205}, abstract = {To uncover molecular determinants of motor neuron degeneration and selective vulnerability in amyotrophic lateral sclerosis (ALS), we generated longitudinal single-nucleus transcriptomes and chromatin accessibility profiles of spinal motor neurons from the SOD1-G93A ALS mouse model. Vulnerable alpha motor neurons showed thousands of molecular changes, marking a transition into a novel cell state we named 'disease-associated motor neurons' (DAMNs). We identified transcription factor regulatory networks that govern how healthy cells transition into DAMNs as well as those linked to vulnerable and resistant motor neuron subtypes. Using spatial transcriptomics, we found reactive glia located near motor neurons early in disease, suggesting early signaling events between motor neurons and glia. Finally, we found that the human orthologs of genomic regions with differential accessibility in SOD1-G93A alpha motor neurons are enriched for single nucleotide polymorphisms associated with human ALS, providing evidence that the genetic underpinnings of motor neuron vulnerability are conserved.}, } @article {pmid40909641, year = {2025}, author = {Dhawka, L and Evangelista, BA and Arooji, OK and Iannone, MA and Pellegrino, K and Traub, R and Li, X and Bedlack, R and Meeker, RB and Cohen, TJ and Stanley, N}, title = {Peripheral immune patterns enable robust cross-platform prediction of ALS onset and progression.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2025.08.26.672381}, pmid = {40909641}, issn = {2692-8205}, abstract = {Amyotrophic lateral sclerosis (ALS) progression rates vary dramatically between patients, yet the basis of this heterogeneity remains elusive, with no prognostic biomarkers existing to guide clinical decisions or stratify patients for therapeutic trials. Here, we identify a network of coordinated immune cell types, which exhibit differential disruption across progression groups. Using mass cytometry (CyTOF) to profile 2.2 million immune cells from 35 ALS patients stratified by progression rate and 9 healthy controls, we find that the extent of immune dysfunction cannot be reflected by examining differences in individual cell type frequencies. In contrast, analyses of correlation patterns between cell types revealed distinct immune organization patterns, where coordination complexity varied with disease progression. Across all progression groups, we observed striking immune reorganization in natural killer (NK) cells and a major shift from B cell/basophil coordination hubs in healthy controls to neutrophil/T cell-dominated patterns in ALS. Having established coordinated immune patterns, we developed machine learning models to further improve our ability to stratify between disease and non-disease cohorts, achieving superior performance compared to models using cell frequencies alone. Central and effector memory (CM/EM) CD4+ T cell interactions emerged as top discriminative features for disease status, while plasmacytoid dendritic cell (pDC) relationships, especially their ratio with regulatory T cells (T-regs), distinguished progression rates, supporting T-reg-based therapeutic approaches. These findings reframe ALS as a disease of immune coordination breakdown, pointing towards cell-type specific therapeutics and biomarkers that may extend beyond ALS to other neurodegenerative diseases characterized by immune dysfunction.}, } @article {pmid40908789, year = {2025}, author = {Carletta, O and Perfetto, C and Rifai, OM and Manganelli, F and Waldron, FM and Maniatis, T and Gregory, JM and Gerbino, V}, title = {Genotype-specific interferon signatures in amyotrophic lateral sclerosis relate to disease severity.}, journal = {Brain : a journal of neurology}, volume = {}, number = {}, pages = {}, doi = {10.1093/brain/awaf324}, pmid = {40908789}, issn = {1460-2156}, abstract = {Innate immune signaling pathways are hyperactivated in the central nervous system (CNS) of patients with Amyotrophic Lateral Sclerosis (ALS), as well as in preclinical models with diverse causative backgrounds including TDP-43, SOD1, and C9orf72 mutations. This raises an important question of whether these pathways are key pathogenic features of the disease, and whether therapeutic amelioration could be beneficial. Here, we systematically profile Type-I interferon (IFN)-stimulated gene (ISG) expression signatures using a non-biased approach in CNS tissue from a cohort of 36 individuals with ALS, including sporadic ALS (sALS; n=18), genetic ALS caused by (i) a C9orf72 hexanucleotide repeat expansion (C9-ALS; n=11), and (ii) a SOD1 mutation (SOD1-ALS; n=5), alongside age- and sex-matched individuals who died of a non-neurological cause (n=12). Using this deeply phenotyped cohort we have implemented targeted transcriptomic analysis and immunohistochemistry to interrogate the nature and extent of the activation of the Type-I IFN response in patients. We determined disease and genotype specific IFN signatures that correlate with clinical phenotype. Correlation analysis linked six ISGs with aggressive disease progression, as indicated by negative correlation with age at death in ALS patients. Notably, significant upregulation of ISGs was observed in C9-ALS patients, with higher ISG expression correlating with shorter disease duration. Noting that our genotype and disease specific signatures correlated with metrics of disease progression, we explored the therapeutic potential of targeting this pathway in a mouse model of ALS. Treatment with an IFN pathway inhibitor reduced IFN response markers, delayed disease progression, including motor decline, and extended survival in ALS mice. We conclude that upregulation of gene expression in the Type-I IFN pathway represents a key pathological feature of ALS and that inhibiting this pathway may provide a promising therapeutic approach for treating ALS.}, } @article {pmid40908745, year = {2025}, author = {Pask, S and Okwuosa, C and Mohamed, A and Price, R and Young, J and Curtis, T and Henderson, S and Winter-Luke, I and Sunny, A and Chambers, RL and Greenley, S and Johansson, T and Bone, AE and Barclay, S and Higginson, IJ and Sleeman, KE and Murtagh, FE}, title = {Models, components and outcomes of palliative and end-of-life care provided to adults living at home: A systematic umbrella review of reviews.}, journal = {Palliative medicine}, volume = {}, number = {}, pages = {2692163251362567}, doi = {10.1177/02692163251362567}, pmid = {40908745}, issn = {1477-030X}, abstract = {BACKGROUND: There is growing demand for home-based palliative care because of patient preference, and increased number of deaths. Optimal models for community-based palliative and end-of-life care are unknown.

AIM: To identify, synthesise and describe review-level evidence to better understand models of palliative and end-of-life care for adults living at home, and examine components of these models and their association with outcomes.

DESIGN: Systematic umbrella review, using key concepts established a priori from Firth et al. and Brereton et al.''s model descriptions. Quality assessment used AMSTAR-2 or equivalent.

DATA SOURCES: MEDLINE, EMBASE, CINAHL, Cochrane Database, Epistemonikos (inception - 2024), supplemented by CareSearch, PROSPERO and citation searches.

RESULTS: From 6683 initial papers, n = 66 reviews were included. Seven models of care were identified; by setting (in-home, outpatient); type of professionals (specialist, integrated, non-specialist); or mode (telehealth, education/training). Components included: holistic person-centred assessment, skilled professionals, access to medicines/care/equipment, patient/family support, advance care planning, integration of services, virtual/remote technology and education. We categorised outcomes into: (i) patient outcomes, (ii) family/informal caregiver outcomes, (iii) professional outcomes and iv) service utilisation/cost outcomes. The 'in-home palliative care' model was most researched with good evidence of positive benefit. Specialist and integrated models of care were next most researched, with evidence of improved patient and service utilisation outcomes. Cost-effectiveness evidence was lacking.

CONCLUSION: This meta-level evidence supports provision of in-home palliative care, with most review level evidence showing positive effect on patient outcomes. There was also evidence to support specialist palliative care and integration of primary palliative care with specialist support.}, } @article {pmid40908710, year = {2025}, author = {Giove, E and Ferraro, PM and Lungu, M and Pasquinelli, L and Truffelli, R and Trinchero, C and Rebagliati, B and Caponnetto, C and Vignolo, M and Rao, F}, title = {Effects of Dog-Assisted Occupational Therapy on Upper Limb Functions in ALS and Other Neuromuscular Disorders: A Randomized Controlled Pilot Study.}, journal = {Muscle & nerve}, volume = {}, number = {}, pages = {}, doi = {10.1002/mus.70012}, pmid = {40908710}, issn = {1097-4598}, abstract = {INTRODUCTION/AIMS: The beneficial effects of animal-assisted therapy (AAT) on balance, walking endurance, and mood symptoms in amyotrophic lateral sclerosis (ALS) have been previously demonstrated. In this study, we aimed at expanding upon these findings by further evaluating its effects on upper limb (UL) functions and mood symptoms both in ALS and other neuromuscular disorders (NMDs).

METHODS: Sixty-eight patients participated in a regular 2-week occupational therapy program once a day. For three days a week, in place of the traditional treatment, the AAT group (N = 34) performed a session in interaction with the therapy dog. Outcome measures included hand grip strength, manual dexterity, and mood symptoms. Differences between baseline and post-treatment values were assessed using the Wilcoxon Signed-Rank Test, and one-way analysis of covariance was used to examine between-group differences in post-treatment values, adjusting for baseline measurements.

RESULTS: Both groups improved in hand grip strength (p = 0.004-0.03), whereas mood symptoms improved exclusively in the AAT group (p = 0.0003-0.03). Post-treatment values were significantly better in the AAT group (p = 0.01-0.03). When ALS patients were analyzed separately, the improvement of hand grip strength and mood symptoms was observed only in the AAT group (p = 0.001-0.04), which accordingly showed better post-treatment values (p = 0.0007-0.05).

DISCUSSION: Our findings indicate that AAT has greater beneficial effects than traditional treatments on UL strength and mood symptoms. These findings have the potential to facilitate more effective rehabilitation strategies both in ALS and other NMDs.}, } @article {pmid40908696, year = {2025}, author = {Paul, S and Tiwari, P and Dubey, S}, title = {Precision Enzyme: Targeted Drug Discovery in Neurodegenerative Disorders.}, journal = {Protein and peptide letters}, volume = {}, number = {}, pages = {}, doi = {10.2174/0109298665391103250825102319}, pmid = {40908696}, issn = {1875-5305}, abstract = {INTRODUCTION: Neurodegenerative disorders such as Alzheimer's, Parkinson's, and ALS are characterized by progressive neuronal dysfunction with limited therapeutic options. Recent advances in molecular biology and drug development have highlighted the therapeutic promise of precision enzyme targeting, offering novel strategies for disease modulation and symptom management.

METHODS: A comprehensive literature review spanning recent/current was conducted using PubMed, Scopus, and ScienceDirect. Studies focusing on enzyme-based targets, high-throughput screening, and molecular docking in neurodegeneration were included. Thematic synthesis was employed to categorize findings based on enzyme class, disease relevance, and therapeutic outcomes.

RESULTS: Key enzyme families such as kinases, proteases, and oxidoreductases were identified as pivotal modulators in disease progression. Emerging enzyme-targeted compounds demonstrated enhanced bioavailability, blood-brain barrier permeability, and disease-specific efficacy. Novel screening platforms and computational modeling enabled the precise selection of inhibitors, significantly improving the therapeutic index and reducing off-target effects.

DISCUSSION: Targeting enzymes implicated in neuroinflammation, oxidative stress, and protein misfolding has shown disease-modifying potential. Integrating precision drug discovery tools, such as AI-assisted modeling and enzyme kinetics, supports rational drug design. However, translational challenges persist due to variability in enzyme expression and disease heterogeneity.

CONCLUSION: Future research should focus on refining enzyme inhibitors and integrating biomarkers to facilitate personalized treatment strategies for neurodegenerative disorders. As the understanding of enzymatic roles in neurodegeneration deepens, precision enzyme-targeted drug discovery holds significant promise in transforming neurotherapeutic approaches.}, } @article {pmid40908144, year = {2025}, author = {Kim, SK and Gelfand, VI}, title = {PolyQ-expansion of Ataxin-2 disrupts microtubule stability and impairs axon outgrowth.}, journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, volume = {}, number = {}, pages = {}, doi = {10.1523/JNEUROSCI.0682-25.2025}, pmid = {40908144}, issn = {1529-2401}, abstract = {Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease characterized by mislocalization and aggregation of proteins in motor neurons. Ataxin-2 (ATXN2), an RNA-binding protein harboring 22-polyglutamine (polyQ) repeats, is a risk factor for ALS, when its polyQ repeats are expanded to 27-33 repeats. However, the physiological function of ATXN2 beyond its role in RNA regulation, and how polyQ expansion in ATXN2 increases risk for ALS, remain unclear. We previously demonstrated that Drosophila Atx2 functions as a regulator of microtubule (MT) dynamics in motor neurons. Here, we uncover the molecular mechanism underlying Atx2-mediated MT regulation and how polyQ expansion disrupts its function, using a mixed-sex population of Drosophila as a model system. Specifically, we show that Atx2 requires its RNA-binding Lsm domain to regulate MTs. Notably, the LSM domains of human ATXN2 rescue MT phenotype in Drosophila, demonstrating an evolutionarily conserved role of ATXN2 in MT regulation. Importantly, we find that polyQ-expanded ATXN2 forms cytoplasmic aggregates and leads to excessive MT destabilization. Additionally, polyQ expansion severely impairs axon outgrowth. Finally, we identify Uncoordinated-76 (UNC-76/FEZ1) as a downstream effector of Atx2 in MT regulation and neuronal development.Significance Statement ALS is a progressive neurodegenerative disease with no effective treatment. Although polyglutamine (polyQ) expansion in the RNA-binding protein ATXN2 is a known risk factor for ALS, its mechanistic role in ALS pathogenesis has remained unclear. We demonstrate that ATXN2 regulates MT dynamics via its RNA-binding domain, and this role is evolutionarily conserved between Drosophila and humans. We further identify UNC-76/FEZ1 as a downstream effector of ATXN2 in regulating MT dynamics and neuronal development. Importantly, this study reveals how polyQ expansion in ATXN2 disrupts MT stability and axon growth, proposing a mechanism that may contribute to increased ALS risk.}, } @article {pmid40908143, year = {2025}, author = {Rodemer, W and Ra, I and Gujral, J and Jia, E and Juul, H and Zhang, B and Hoxha, K and Xing, B and Mehta, S and Farag, M and Rekulak, S and Porta, S and Jensen, FE and Talos, DM and Lee, VM}, title = {Network dysfunction precedes neurodegeneration in a dox-regulatable TDP-43 mouse model of ALS-FTD.}, journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, volume = {}, number = {}, pages = {}, doi = {10.1523/JNEUROSCI.2297-24.2025}, pmid = {40908143}, issn = {1529-2401}, abstract = {Neuronal hyperexcitability is a hallmark of amyotrophic lateral sclerosis (ALS) but its relationship with the TDP-43 aggregates that comprise the predominant pathology in over 90% of ALS cases remains unclear. Emerging evidence indicates that TDP-43 pathology induces neuronal hyperexcitability, which may contribute to excitotoxic neuronal death. To characterize TDP-43 mediated network excitability changes in a disease-relevant model, we performed in vivo continuous electroencephalography monitoring and ex vivo acute hippocampal slice electrophysiology in rNLS8 mice (males and females), which express human TDP-43 with a defective nuclear localization signal (hTDP-43ΔNLS). Surprisingly, we identified the presence of seizures in approximately 64% of rNLS8 mice beginning around 2.5 weeks after transgene induction (off-DOX). More broadly, we observed longitudinal changes in cortical EEG patterns and circuit hyperexcitability preceding neurodegeneration of vulnerable hippocampal subfields. Consistent with previous reports, we have observed broad dysregulation of AMPA subunit expression in mice expressing hTDP-43ΔNLS. These changes were most pronounced in the hippocampus, where we hypothesized they promote hyperexcitability and ultimately, excitotoxic cell death. Interestingly, hippocampal injection of AAV encoding inhibitory DREADDs (hM4Di) and daily activation with CNO ligand rescued anxiety deficits on the elevated zero maze but did not reduce neurodegeneration. Moreover, therapeutic doses of the anti-seizure medications, valproic acid and levetiracetam, did not improve behavior or prevent neurodegeneration. These results highlight the complex relationship between TDP-43 -mediated neuronal hyperexcitability and neurodegeneration. Although targeting hyperexcitability may ameliorate some behavioral deficits, our study suggests it may not be sufficient to halt or slow neurodegeneration in TDP-43-related proteinopathies.Significance Statement Cytoplasmic aggregates of TDP-43 are the predominant pathology in over 90% of ALS and 50% of frontotemporal lobar degeneration cases. Understanding how TDP-43 pathology promotes neurodegeneration may lead to therapeutic strategies to slow disease progression in humans. In this study, we identified hippocampal network hyperexcitability and generalized seizures that preceded neurodegeneration in the inducible rNLS8 mouse model. Local suppression of hippocampal hyperexcitability with chemogenetics (hM4Di) improved behavioral function but did not reduce neuron loss. Systemic anti-seizure medications had no beneficial effects. These results highlight the complexity of TDP-43 induced excitability changes but ultimately suggest that directly targeting hyperexcitability may not be therapeutically effective.}, } @article {pmid40907612, year = {2025}, author = {Kumar, AP and Puthussery, DT}, title = {Regulation of PPAR-γ coactivator-1α and its implication in mitochondrial function and neurodegenerative diseases.}, journal = {Ageing research reviews}, volume = {112}, number = {}, pages = {102887}, doi = {10.1016/j.arr.2025.102887}, pmid = {40907612}, issn = {1872-9649}, abstract = {Peroxisome proliferator-activated receptor (PPAR)-γ coactivator (PGC)-1α, interacts with numerous transcription factors implicated in a wide spectrum of biological responses. It has been identified as a key player in the transcriptional regulation of many mitochondrial components. The activity of PGC1-α is regulated at multiple levels, such as gene expression, transcriptional, post-transcriptional, and post-translational modification. The purpose of this review is to highlight the data supporting PGC1-α-mediated regulation by transcriptional and post-translational modification. We summarize the mechanisms involved in PGC1-α regulation by phosphorylation (AMPK, p38 MAPK, Akt, and GSK3β), acetylation (GCN5, p300, and SRCC), and ubiquitination (E3-ubiquitin ligase). Moreover, the review focuses on the multidomain structure of PGC1-α, its expression in the brain, and the importance of PGC1-α-mediated mitochondrial functions. Mitochondrial dysfunction and impaired energy metabolism are key characteristics of neurodegenerative diseases like Alzheimer's, Huntington's, Parkinson's, amyotrophic lateral sclerosis, and multiple sclerosis. It is associated with reduced PGC1-α expression or activity, resulting in an imbalance in the maintenance of mitochondrial dynamics. In this backdrop, we additionally provide a comprehensive overview of the implication of PGC1-α in the pathogenesis of neurodegenerative disease. Overall, PGC1-α acts as a potential target for therapies to reduce mitochondrial dysfunction associated with neurodegenerative diseases and aid in neuroprotection.}, } @article {pmid40906916, year = {2025}, author = {Kakoty, V and Kang, JH and Lee, OH and Oh, DH and Ko, YT}, title = {Grueneberg Ganglion: An Unexplored Site for Intranasal Drug Delivery in Alzheimer's Disease.}, journal = {ACS chemical neuroscience}, volume = {}, number = {}, pages = {}, doi = {10.1021/acschemneuro.5c00376}, pmid = {40906916}, issn = {1948-7193}, abstract = {Neurological disorders such as Alzheimer's Disease, Parkinson's Disease, Huntington's Disease, Multiple Sclerosis, and Amyotrophic Lateral Sclerosis pose significant challenges for treatment. Reasons for the difficulty in finding cures for these conditions include complications in early diagnosis, progressive and irreversible neuronal damage, and the presence of the blood-brain barrier (BBB), which hinders the delivery of drugs to the affected areas of the brain. Intranasal (INL) drug administration has increasingly gained popularity among researchers for targeting neurological conditions, because of its ability to bypass the BBB. However, chronic INL administration leads to nasal mucosa irritation. Additionally, rapid mucociliary clearance, a lack of targeted drug delivery, increased enzymatic degradation, and tight junctions that obstruct drug transport limit the clinical applicability of the INL route. To overcome these challenges, a unique region in the rodent nose, known as the Grueneberg Ganglion (GG), can be considered to be a novel site for INL drug administration. GG is a small structure housed under the snout cartilage of the nasal septum, approximately 1.5 mm from the nasal opening in mice. It is directly connected to the main olfactory bulb through axons. This Perspective aims to expand knowledge on why GG may be a viable option for INL delivery to combat neurological conditions. For better understanding, we have explained the INL administration in GG, using Alzheimer's Disease and INL insulin therapy as a role model for the current review.}, } @article {pmid40906311, year = {2025}, author = {Oubari, H and Berkane, Y and Jeljeli, M and Lellouch, AG and Smadja, DM}, title = {Engineering the Future of Stem Cells in Vascular Reconstruction: A Leap Towards Functional Endothelialized Tissue-Engineered Vascular Conduits.}, journal = {Stem cell reviews and reports}, volume = {}, number = {}, pages = {}, pmid = {40906311}, issn = {2629-3277}, abstract = {The transition from reconstructive to regenerative strategies in vascular surgery has intensified the need for grafts that are biocompatible, growth-capable, and resistant to thrombosis. Addressing this challenge, Park et al. introduce a groundbreaking method for engineering fully biological, endothelialized tissue-engineered vascular conduits (TEVCs) using decellularized human umbilical arteries (dHUAs) coated with human induced pluripotent stem cell-derived endothelial cells (hiPSC-ECs). These constructs undergo shear stress training in bioreactors, mimicking physiological blood flow to enhance endothelial functionality and anti-thrombotic properties. Upon implantation in animal models, the grafts showed long-term patency, resistance to thrombosis, and progressive replacement of hiPSC-ECs by host endothelial cells, highlighting their regenerative and integrative potential. The study emphasizes the pivotal role of hemodynamic conditioning and key regulators such as KLF2 in promoting endothelial quiescence and vascular homeostasis. It further explores alternative strategies like endothelial colony-forming cells (ECFCs) and microfluidic systems for flow-induced maturation. Clinically, this approach offers a promising, scalable avenue for patient-specific, immune-compatible vascular grafts applicable in congenital heart disease, dialysis access, vascular grafts and coronary bypass. While challenges such as long-term durability and mechanical reinforcement remain, this research marks a transformative step toward functional, off-the-shelf vascular grafts. Park et al.'s work bridges biomimicry with regenerative medicine, paving the way for next-generation vascular therapies rooted in endothelial mechanobiology and personalized bioengineering.}, } @article {pmid40906043, year = {2025}, author = {García-Toledo, I and Godoy-Corchuelo, JM and Fernández-Beltrán, LC and Ali, Z and Guindo-Arroyo, A and Jiménez-Coca, I and Jiménez-Rodríguez, J and Javaloyes-García, K and Viñuela, M and Gómez-Pinedo, U and Saiz-Aúz, L and Rábano, A and Área-Gómez, E and Cunningham, TJ and Corrochano, S}, title = {TDP-43 dysregulation impairs cholesterol metabolism linked with myelination defects.}, journal = {Acta neuropathologica}, volume = {150}, number = {1}, pages = {23}, pmid = {40906043}, issn = {1432-0533}, support = {PIPF-2022/SAL-GL-24282//Consejería de educación, ciencia y universidades, Comunidad de Madrid/ ; PDI2020-1153-70RB-100//Ministerio de Ciencia e Innovación/ ; PID2023-147947OB-I00//Ministerio de Ciencia e Innovación/ ; CT58/21-CT59/21//Unversidad Complutense de Madrid/ ; }, mesh = {*Cholesterol/metabolism ; Animals ; *DNA-Binding Proteins/metabolism/genetics ; *Myelin Sheath/metabolism/pathology ; Mice ; Humans ; *TDP-43 Proteinopathies/metabolism/pathology/genetics ; Male ; Brain/metabolism/pathology ; Mice, Transgenic ; Female ; Mice, Inbred C57BL ; Lipid Metabolism ; Frontal Lobe/metabolism/pathology ; Disease Models, Animal ; }, abstract = {TDP-43 is a nuclear protein encoded by the TARDBP gene, which forms pathological aggregates in various neurodegenerative diseases, collectively known as TDP-43 proteinopathies, including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). These diseases are characterized by multiple pathological mechanisms, with disruptions in lipid regulatory pathways emerging as a critical factor. However, the role of TDP-43 in the regulation of the brain lipid homeostasis and the potential connection of TDP-43 dysfunction to myelin alterations in TDP-43 proteionopathies remain poorly understood, despite the fact that lipids, particularly cholesterol, comprise nearly 70% of myelin. To investigate the causal relationship between TDP-43 dysfunction and disruptions in brain cholesterol homeostasis, we conducted multi-omics analyses (lipidomics, transcriptomics, and functional splicing) on the frontal cortex from the Tardbp[M323K/M323K] knock-in mouse model. Lipidomic analysis revealed alterations in lipid pathways related to membrane composition and lipid droplet accumulation, particularly affecting cholesterol-related species. We found higher lipid droplet accumulation in primary fibroblasts derived from these mice, as well as in the brain of the mutant mice. Similarly, the immunohistochemical detection of a lipid droplet marker was higher in the postmortem frontal cortex, gray matter, and white matter of FTLD-TDP patients compared to non-neurological controls. Transcriptomic analyses showed that TDP-43 pathology led to transcriptional dysregulation of genes essential for myelin production and maintenance. We identified impaired cholesterol metabolism, mainly through the downregulation of endogenous cholesterol synthesis, alongside upregulated cholesterol transport pathways, which we further replicated in FTLD-TDP patients transcriptomic datasets. Collectively, our findings suggest that TDP-43 dysfunction disrupts brain cholesterol homeostasis, potentially compromising myelin integrity.}, } @article {pmid40906007, year = {2025}, author = {Howard-Williams, EL and Ossman, P and Fuller, J}, title = {Respiratory-Onset Amyotrophic Lateral Sclerosis (ALS): A Rare Initial Presentation.}, journal = {Journal of general internal medicine}, volume = {}, number = {}, pages = {}, pmid = {40906007}, issn = {1525-1497}, } @article {pmid40905788, year = {2025}, author = {Willemse, SW and Demaegd, KC and Van Eijk, RPA and Van Damme, P and Harrington, E and Harms, MB and Shneider, NA and Van Rheenen, W and Veldink, JH and Van Den Berg, LH and Van Es, MA}, title = {A VAPB (P56S) mutation in a Dutch patient with familial motor neuron disease: a case report.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {}, number = {}, pages = {1-3}, doi = {10.1080/21678421.2025.2555218}, pmid = {40905788}, issn = {2167-9223}, abstract = {The c.166C > T p.(Pro56Ser) or P56S mutation in the VAPB gene was initially identified as a cause of motor neuron disease in Brazil in a large extended pedigree comprising >1,500 individuals including more than 200 cases. This VAPB mutation gives rise to three phenotypes: late-onset spinal muscular atrophy, classical ALS with bulbar involvement, pyramidal signs and rapid disease progression, and atypical ALS with slow progression. Nearly all known cases originate from a single founder, with most cases outside of Brazil being related to this pedigree. However, there is one report of an independent German family with the same mutation on a different haplotype, indicating a second founder event. Here, we report the first Dutch patient with a P56S mutation in VAPB and motor neuron disease. Documenting rare genetic causes of MND and their natural history are of increasing importance in light of emerging gene-specific therapies.}, } @article {pmid40905723, year = {2025}, author = {Peng, C and Maiuri, T and Truant, R}, title = {Tipping the PARylation scale: Dysregulation of PAR signaling in Huntington and neurodegenerative diseases.}, journal = {Journal of Huntington's disease}, volume = {}, number = {}, pages = {18796397251372667}, doi = {10.1177/18796397251372667}, pmid = {40905723}, issn = {1879-6400}, abstract = {Poly(ADP-ribosyl)ation (PARylation), a crucial post-translational modification, is catalyzed by ADP-ribosyltransferases (ARTs) and has significant implications in various cellular processes, including DNA damage response, cell signaling, and immune processes. Aberrant PAR signaling is implicated in numerous neurodegenerative diseases, including Alzheimer, Parkinson, amyotrophic lateral sclerosis, and cerebellar ataxia, where increased PAR levels and PARP1 activity are commonly observed. However, Huntington disease exhibits a unique characteristic: reduced PAR levels and impaired PARP1 activity even in prodromal phase. This finding challenges the prevailing understanding of PAR's role in neurodegeneration and suggests that dysregulation of PAR signaling, whether through overactivation or suppression, can lead to neuronal dysfunction. Herein, we discuss how this balance may impact neurodegenerative diseases, and possible connections between PAR signaling and emerging modifiers of disease onset identified by HD genome-wide association studies (GWAS).}, } @article {pmid40905633, year = {2025}, author = {Verdés, S and Navarro, X and Bosch, A}, title = {Targeting Amyotrophic Lateral Sclerosis with Gene Therapy: From Silencing Genes to Enhancing Neuroprotection.}, journal = {Human gene therapy}, volume = {}, number = {}, pages = {}, doi = {10.1177/10430342251372898}, pmid = {40905633}, issn = {1557-7422}, abstract = {Gene therapy is emerging as a transformative approach for treating amyotrophic lateral sclerosis (ALS), a progressive and fatal neurodegenerative disease. While gene replacement has shown a groundbreaking success in spinal muscular atrophy, the complexity of ALS-due to frequent gain-of-function mutations and a heterogeneous etiology-presents significant challenges. Importantly, approximately 90% of ALS cases are sporadic, with unknown genetic mutation, further complicating patient stratification and therapeutic targeting. As a result, gene therapy strategies must often address multiple pathological mechanisms simultaneously. So far, current gene therapy strategies aim to either suppress toxic gene expression or promote neuroprotection, predominantly via viral-mediated delivery systems. This review will provide an overview of emerging preclinical and clinical gene therapy approaches for ALS, focusing on two main strategies: gene silencing and neuroprotection. Gene silencing techniques, including antisense oligonucleotides (ASOs), viral-mediated RNA interference, and gene editing, have demonstrated efficacy in reducing mutant gene expression, particularly in SOD1 and C9orf72 models, although clinical translation has so far yielded limited success. The recent Food and Drug Administration's approval of the ASO therapy Qalsody for SOD1-ALS underscores the clinical potential of these approaches. Neuroprotective strategies aim to enhance motor neuron survival through delivery of trophic factors, often targeting both central and peripheral tissues to harness retrograde transport mechanisms. We will discuss the advantages and limitations of various delivery vectors, targeting specificity, timing of intervention, and translational challenges, alongside current clinical trial data. This review aims to synthesize how these approaches may converge to address the multifaceted nature of ALS and guide the development of next-generation therapeutics.}, } @article {pmid40905501, year = {2025}, author = {Huang, Y and Wan, Y and Chen, J and Qin, M and Wang, J and Liang, H}, title = {Knowledge mapping of biomarkers in amyotrophic lateral sclerosis: a comprehensive bibliometric and visual analysis.}, journal = {Neurodegenerative disease management}, volume = {}, number = {}, pages = {1-17}, doi = {10.1080/17582024.2025.2554525}, pmid = {40905501}, issn = {1758-2032}, abstract = {BACKGROUND: Amyotrophic Lateral Sclerosis (ALS) is a severe neurodegenerative disease, and there is currently an urgent need to identify valuable biomarkers to accelerate diagnosis, optimize treatment and prognosis.

METHODS: To conduct a bibliometric analysis of publications related to "ALS biomarker" over the past 20 years, utilizing the subject search feature of the Web of Science Core Collection along with CiteSpace, VOSviewer, and Bibliometrix.

RESULTS: This review presents a 20-year bibliometric analysis of ALS biomarker research (2004-2024), analyzing 2535 publications showing rising trends. The United States led contributions, with Turner, Martin R as the most productive/cited author. Key research hotspots included cerebrospinal fluid, tdp-43, clinical trial, and neuroinflammation. Topics such as neurofilament light chain, machine learning, and exosomes could potentially represent the cutting edge of future research.

CONCLUSION: In summary, this study uses bibliometric analysis of ALS biomarker research to provide a forward-looking perspective on its future limitations and potential.}, } @article {pmid40904817, year = {2025}, author = {Kuo, T and Reynolds, T and Chen, L and Park, C and Rascati, K and Godley, P}, title = {Racial and ethnic disparities in ALS: a longitudinal electronic health records study.}, journal = {Therapeutic advances in neurological disorders}, volume = {18}, number = {}, pages = {17562864251365001}, pmid = {40904817}, issn = {1756-2856}, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease with limited treatment options and significant variability in care. Racial and ethnic disparities in ALS management and outcomes have been reported, but findings remain inconsistent.

OBJECTIVES: This study aimed to evaluate racial and ethnic disparities in ALS care, specifically differences in healthcare utilization, treatment patterns, and survival, within a large healthcare system.

DESIGN: This retrospective cohort study analyzed electronic health records from a large healthcare system in Texas for patients diagnosed with ALS between 2013 and 2023, examining racial and ethnic differences in treatment and outcomes.

METHODS: Patients were identified using International Classification of Diseases (ICD) codes. Baseline characteristics, including race/ethnicity and socioeconomic factors, were collected. Primary outcomes included the use of noninvasive ventilation (NIV), tracheostomy, gastrostomy, mobility aids, and ALS medications; secondary outcomes included time to diagnosis and survival. Racial and ethnic disparities were assessed using generalized linear regression and Cox proportional hazards models, adjusting for demographic and socioeconomic factors.

RESULTS: A total of 636 patients were included (74.5% Non-Hispanic White, 5.3% Non-Hispanic Black, 7.4% Hispanic, and 12.7% Other). Non-Hispanic Black patients had significantly higher tracheostomy rates than Non-Hispanic White patients (35.3% vs 8.7%; adjusted odds ratio (OR), 6.20; 95% confidence interval (CI), 2.43-15.84). Hispanic patients had lower odds of receiving riluzole (42.6% vs 61.8%; adjusted OR, 0.36; 95% CI, 0.18-0.71) and higher rates of emergency department visits (adjusted OR, 2.00; 95% CI, 1.09-3.65) and hospitalizations (adjusted OR, 2.57; 95% CI, 1.37-4.81). No significant racial or ethnic differences were observed in time to diagnosis or survival after adjustment.

CONCLUSION: Significant racial and ethnic disparities exist in ALS care, particularly in tracheostomy utilization, medication prescribing, and healthcare access. These findings underscore the need for targeted interventions to promote equitable ALS management, including provider education and improved healthcare accessibility.}, } @article {pmid40904199, year = {2025}, author = {Isik, S and Osman, S and Yeman-Kiyak, B and Shamshir, SRM and Sanchez, NME}, title = {Advances in Neurodegenerative Disease Therapy: Stem Cell Clinical Trials and Promise of Engineered Exosomes.}, journal = {CNS neuroscience & therapeutics}, volume = {31}, number = {9}, pages = {e70577}, doi = {10.1111/cns.70577}, pmid = {40904199}, issn = {1755-5949}, mesh = {Humans ; *Exosomes/transplantation/metabolism ; *Neurodegenerative Diseases/therapy ; Animals ; *Stem Cell Transplantation/methods/trends ; *Clinical Trials as Topic/methods ; }, abstract = {AIM: This review provides a systematic evaluation of 94 stem cell clinical trials to treat neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease.

METHODS: Data were collected from using relevant search terms, focusing exclusively on stem cell therapy. Of the 8000+ participants in these trials, nearly 70% were enrolled in AD-related studies. Only three Phase 3 studies were conducted, and most trials were in the early phases (Phases 1 and 2). Mesenchymal stem cells, neural stem cells, induced pluripotent stem cells, and embryonic stem cells are used the most to treat neurodegenerative diseases. This review also explores the emerging fields of preclinical and clinical investigations of stem cell-derived exosome-based therapies for neurodegenerative diseases.

RESULTS: Exosomes can cross the blood-brain barrier to deliver therapeutic molecules directly to the brain, offering a less invasive alternative to stem cell transplantation. Mesenchymal stem cell-derived exosomes, in particular, have demonstrated significant potential in preclinical models by reducing neuroinflammation, oxidative stress, and promoting neuronal regeneration. Additionally, recent advances in exosome engineering, including surface modifications, therapeutic agent loading, and transgenic modifications, have improved targeting, stability, blood-brain barrier delivery, and neural cell interactions, enabling targeted and effective treatment. Exosome-based therapies are in the preliminary phases of clinical investigation, with only three clinical trials.

CONCLUSION: Given the increasing interest in exosome therapy, clinical investigations are expected to increase. This growth will be driven by ongoing advancements in exosome technology, a deeper understanding of their therapeutic potential, and escalating demand for innovative treatment strategies for neurodegenerative diseases.}, } @article {pmid40903966, year = {2025}, author = {Abbassi, Y and Fink, D and Cei, F and Niccolai, E and Amedei, A}, title = {TDP-43-immunity-microbiota axis in amyotrophic lateral sclerosis: A potential pathogenic mechanism.}, journal = {Neural regeneration research}, volume = {}, number = {}, pages = {}, doi = {10.4103/NRR.NRR-D-25-00440}, pmid = {40903966}, issn = {1673-5374}, abstract = {Amyotrophic lateral sclerosis is a devastating neurodegenerative disease marked by progressive motor neuron degeneration. Despite extensive research, effective treatments remain elusive, underscoring the need to explore the molecular mechanisms driving disease progression. The amyotrophic lateral sclerosis complexity is further compounded by its large heterogeneity, encompassing both genetic and sporadic forms, diverse phenotypic presentations, and highly variable progression rates. A key pathological feature of amyotrophic lateral sclerosis is the aggregation of TAR DNA-binding protein 43, which contributes to cellular toxicity, neuroinflammation, and neuronal dysfunction. This review explores the complex interplay between TAR DNA-binding protein 43 pathology, immunity dysregulation, and the gut-brain axis, with a focus on the role of microbiome-derived metabolites in amyotrophic lateral sclerosis. Neuroinflammation, mediated by both innate and adaptive immunity, plays a central role in disease pathogenesis, with TAR DNA-binding protein 43 influencing immune signaling and exacerbating neurotoxicity. Additionally, disruptions in gut microbiota composition and intestinal barrier integrity, frequently observed in amyotrophic lateral sclerosis patients, suggest a potential role for the gut-brain axis in modulating neurodegenerative processes. By integrating evidence from emerging studies, our aim is to clarify how TAR DNA-binding protein 43 aggregation contributes to neuroinflammation and immune dysfunction while exploring the gut microbiota role as both a modulator and potential biomarker of disease. Understanding these interactions could pave the way for novel therapeutic strategies, including microbiome-targeted interventions such as probiotics, dietary modifications, or immune-modulating therapies. Finally, unraveling the TAR DNA-binding protein 43-immune system-microbiome axis may offer new avenues for personalized treatments aimed at mitigating neuroinflammation, slowing amyotrophic lateral sclerosis progression, and improving patient outcomes and life quality.}, } @article {pmid40903965, year = {2025}, author = {Parikh, A and Cholavaram, A and Chitti Babu, AK and Deepankumar, K and Vijayan, M}, title = {Role of voltage-dependent anion channel 1 in neurodegeneration: Mechanisms, implications, and therapeutic potential.}, journal = {Neural regeneration research}, volume = {}, number = {}, pages = {}, doi = {10.4103/NRR.NRR-D-25-00368}, pmid = {40903965}, issn = {1673-5374}, abstract = {Voltage-dependent anion channel 1 is an integral outer membrane protein of the mitochondria that governs apoptosis, enables metabolite exchange, and influences mitochondrial activity. In neurodegenerative diseases, such as amyotrophic lateral sclerosis, Parkinson's disease, Huntington's disease, and Alzheimer's disease, oxidative stress, neuroinflammation, and mitochondrial dysfunction are frequent features. Voltage-dependent anion channel 1 is a key regulator of these processes. This review described the structure, membrane topology, and physiological function of voltage-dependent anion channel 1 in neurons and glial cells. We emphasize how it affects mitophagy, oxidative damage, and changes in mitochondrial permeability. Special attention is focused on how voltage-dependent anion channel 1 interacts with pathogenic proteins that damage mitochondrial integrity and cause neurotoxicity, including mutant huntingtin, phosphorylated tau, α-synuclein, amyloid-beta, and TAR DNA-binding protein 43. Furthermore, the paper examines the function of voltage-dependent anion channel 1 in astrocytic dysfunction and microglial activation, highlighting its impact on neuroinflammation. In a nutshell, we assess treatment strategies that target voltage-dependent anion channel 1, such as VBIT-4, a selective inhibitor of voltage-dependent anion channel 1 oligomerization, and newer methods, including structure-based drug design and CRISPR/Cas9 regulation. Improved knowledge of the hinter voltage-dependent anion channel 1 of the molecular mechanism may allow for new therapeutic approaches in neurodegenerative diseases.}, } @article {pmid40903956, year = {2025}, author = {Chen, Y and Yin, P and Chen, Q and Zhang, Y and Tang, Y and Jin, W and Yu, L}, title = {Neurodegenerative diseases and immune system: From pathogenic mechanism to therapy.}, journal = {Neural regeneration research}, volume = {}, number = {}, pages = {}, doi = {10.4103/NRR.NRR-D-25-00274}, pmid = {40903956}, issn = {1673-5374}, abstract = {Neurodegenerative diseases are a class of disorders with the gradual loss of the central nervous system and peripheral nervous system. Neurodegenerative diseases manifest primarily as cognitive and behavioral disorders that adversely affect the lives of millions of people worldwide. Therefore, it is necessary to elucidate the mechanism of neurodegenerative diseases further and find effective new therapies. In recent years, increasing evidence has shown that the immune system plays a significant role in the pathophysiology of neurodegenerative diseases and regulates this process. The central and peripheral immune systems exert different roles in the disease progression. The development of neurodegenerative diseases is influenced by interactions between them. This review focuses on how the immune system, including microglia mediated nucleotide-binding oligomerization domainlike receptor protein 3 inflammation activation and T cell-mediated neuroinflammation, interactions with neurodegenerative diseases by modulating protein aggregation and blood-brain barrier permeability. Besides, we gave particular attention to glial cell-centered multicellular interactions and the inflammatory signaling pathway. Insight into the immune system's functions and cellular interactions is essential for progressing disease research. In addition, the functions and mechanisms of these immune cells also suggest new ideas and targets for treatment. Therefore, this review summarizes some of the existing treatment strategies for amyloid-beta, tau, neuroinflammation, α-synuclein, associated microbiota, immune modulation, and neural injury repair. In addition, this review summarizes and compares animal models of different common neurodegenerative diseases and clinical research progress. In view of the current research status, new research directions and suggestions are proposed.}, } @article {pmid40903950, year = {2025}, author = {Liu, Y and Tang, T and Cai, H and Liu, Z}, title = {Bidirectional communication between the gut microbiota and the central nervous system.}, journal = {Neural regeneration research}, volume = {}, number = {}, pages = {}, doi = {10.4103/NRR.NRR-D-25-00434}, pmid = {40903950}, issn = {1673-5374}, abstract = {In recent years, an increasing number of researchers have become interested in the bidirectional communication between the gut microbiota and the central nervous system. This communication occurs through the microbiota-gut-brain axis. As people age, the composition of the gut microbiota undergoes considerable changes, which are now known to play an important role in the development of many neurodegenerative diseases. This review aims to investigate the complex bidirectional signaling pathways between the gut and the brain. It summarizes the latest research findings on how the gut microbiota and its metabolites play critical roles in regulating inflammation, maintaining gut health, and influencing the development of neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. The review also analyzes the current clinical applications of gut microbiota-based treatments for neurological disorders, including fecal microbiota transplantation, probiotics, and prebiotics. Many studies show that the gut microbiota affects the brain in several ways. For example, it can produce substances such as short-chain fatty acids and activate inflammatory pathways. Studies involving animals and laboratory models have demonstrated that adjusting the gut microbiota can help improve behavior and reduce neurological problems. Recent metagenomic and metabolomics studies have shown that the microbiota plays a crucial role in maintaining the organism's health. Microorganisms primarily colonize the gut and are involved in host nutrient metabolism, maintaining the structural integrity of the intestine, preserving the intestinal mucosal barrier, and modulating the immune system. The gut microbiota communicates with the brain through a bidirectional microbiota-gut-brain axis. The composition of the gut flora changes considerably with age, and ecological dysregulation has been recognized as one of the twelve most recent hallmarks of aging. Recent studies have linked these changes to a variety of age-related neurological disorders, including Alzheimer's disease, amyotrophic lateral sclerosis, Parkinson's disease, multiple sclerosis, and Huntington's disease. Specifically, the gut microbiota influences the brain through the production of key metabolites such as short-chain fatty acids and the activation of inflammatory and other relevant signaling pathways. In preclinical studies, targeted modulation of the gut microbiota, through methods such as fecal microbiota transplantation, probiotics, and prebiotics, has demonstrated potential in improving host behavioral outcomes. Therefore, gut microbiotabased treatments offer new hope for the treatment of nervous system diseases. However, due to the complexity of the gut microbiota and the potential adverse reactions associated with these therapies, researchers need to carefully assess their safety and efficacy before widespread clinical application.}, } @article {pmid40903937, year = {2025}, author = {Martinez, P and van Zundert, B and Bustos, FJ}, title = {Reevaluating the role of skeletal muscle in amyotrophic lateral sclerosis pathogenesis: Insights from muscle-derived factors.}, journal = {Neural regeneration research}, volume = {}, number = {}, pages = {}, doi = {10.4103/NRR.NRR-D-25-00567}, pmid = {40903937}, issn = {1673-5374}, } @article {pmid40903936, year = {2025}, author = {Shao, N and Zhang, X and Ge, Y and Tang, J and Gao, H and Si, W and Cai, B}, title = {O-GlcNAcylation: A molecular switch linking brain health to neurodegeneration.}, journal = {Neural regeneration research}, volume = {}, number = {}, pages = {}, doi = {10.4103/NRR.NRR-D-25-00101}, pmid = {40903936}, issn = {1673-5374}, abstract = {Neurodegenerative disorders are typically caused by harmful protein accumulation and nerve cell damage. A post-translational modification called O-linked N-acetylglucosamine ylation acts as a critical regulator in these disorders by controlling protein behavior, cell signaling, and energy balance. This modification is dynamically balanced through the cooperative actions of O-linked N-acetylglucosamine transferase and O-GlcNAcase. In healthy brains, O-GlcNAcylation supports nerve cell function and survival, but its imbalance contributes to disease progression. Notably, the effects of O-GlcNAcylation differ across disorders. This review reveals how O-GlcNAcylation bridges molecular mechanisms to neurodegeneration, as well as the prospects of targeted O-linked N-acetylglucosamine acylation therapy for neurodegenerative diseases. In Alzheimer's disease, it blocks toxic changes in key proteins like tau and amyloid-beta. In Parkinson's disease, it reduces the clumping of alpha-synuclein, yet may disrupt dopamine production. In amyotrophic lateral sclerosis, it protects nerve fiber transport systems. Additionally, O-GlcNAcylation plays an indispensable part in other neurodegenerative conditions, including Huntington's disease, aging, Machado-Joseph disease, multiple sclerosis, and giant axonal neuropathy. New therapies targeting this mechanism include glucosamine supplements and O-GlcNAcase inhibitors, which show clinical promise but face translational challenges.}, } @article {pmid40903652, year = {2025}, author = {Koyuncu, S and Dominguez-Canterla, Y and Alis, R and Salarzai, N and Petrovic, D and Flames, N and Vilchez, D}, title = {The aging factor EPS8 induces disease-related protein aggregation through RAC signaling hyperactivation.}, journal = {Nature aging}, volume = {}, number = {}, pages = {}, pmid = {40903652}, issn = {2662-8465}, support = {VI742/4-2//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; EXC 2030-390661388//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; 0.22.2.030MN//Fritz Thyssen Stiftung (Fritz Thyssen Foundation)/ ; CIAICO/2022/195//Generalitat Valenciana (Regional Government of Valencia)/ ; }, abstract = {Aging is a major risk factor for neurodegenerative diseases associated with protein aggregation, including Huntington's disease and amyotrophic lateral sclerosis (ALS). Although these diseases involve different aggregation-prone proteins, their common late onset suggests a link to converging changes resulting from aging. In this study, we found that age-associated hyperactivation of EPS8/RAC signaling in Caenorhabditis elegans promotes the pathological aggregation of Huntington's disease-related polyglutamine repeats and ALS-associated mutant FUS and TDP-43 variants. Conversely, knockdown of eps-8 or RAC orthologs prevents protein aggregation and subsequent deficits in neuronal function during aging. Similarly, inhibiting EPS8 signaling reduces protein aggregation and neurodegeneration in human cell models. We further identify the deubiquitinating enzyme USP4 as a regulator of EPS8 ubiquitination and degradation in both worms and human cells. Notably, reducing USP-4 upregulation during aging prevents EPS-8 accumulation, extends longevity and attenuates disease-related changes. Our findings suggest that targeting EPS8 and its regulatory mechanisms could provide therapeutic strategies for age-related diseases.}, } @article {pmid40903341, year = {2025}, author = {Vedula, P and Ishizuka, K and Hayashida, A and Sueo, K and Sawa, A}, title = {Stress-induced nuclear GAPDH: Scientific update and clinical application.}, journal = {Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics}, volume = {}, number = {}, pages = {e00725}, doi = {10.1016/j.neurot.2025.e00725}, pmid = {40903341}, issn = {1878-7479}, abstract = {Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) is known as a moonlighting protein beyond its original glycolytic function. Stress-induced nuclear translocation of GAPDH has been reproducibly reported, which results in variety types of cellular responses, including cell death and dysfunction. Blocking this stress-induced cascade has been regarded as a target of drug discovery and development for human disease conditions, particularly for neurological and psychiatric diseases. There are promising small compounds that can block this cascade in cell and animal models. Nevertheless, the clinical trials for Parkinson's disease and amyotrophic lateral sclerosis with one of these compounds Omigapil were unsuccessful. Including these failure cases, this review article discussed the scientific frontline of GAPDH, particularly stress-induced nuclear GAPDH, and its potential for clinical applications.}, } @article {pmid40903205, year = {2025}, author = {Ng, L and Sweeney, KD and Mercer, SW}, title = {Challenges in reducing the 10-item CARE measure to a two-item version: comparison of patients' preferences with psychometric evaluation in a cross-sectional survey in Scotland.}, journal = {BJGP open}, volume = {}, number = {}, pages = {}, doi = {10.3399/BJGPO.2025.0085}, pmid = {40903205}, issn = {2398-3795}, abstract = {BACKGROUND: The Consultation and Relational Empathy (CARE) Measure is a widely used 10-item measure to assess patients' perceptions of physician empathy. Takahashi et al.'s (2022) recent study proposed a two-item version based on psychometric evaluation of survey responses, without considering patient preferences.

AIM: To apply Takahashi et al's psychometric method to UK data, and compare findings with patients' preferences on the two most important items.

DESIGN AND SETTING: In 2022, a cross-sectional postal survey of 6,291 Scottish adults was conducted.

METHOD: Using Takahashi et al..'s method, psychometric evaluation compared correlations between all possible two-item combinations with the original 10-item CARE measure to identify the optimal two-item combination. Patients were also asked to select the two items they considered most important. Descriptive analysis examined the proportion of patients selecting each item, and level of agreement on the most popular two-item combination.

RESULTS: 1053 (17%) of 6,291 patients responded. Psychometric evaluation identified items 6 ("Showing care and compassion") and 8 ("Explaining things clearly") as the optimal two-item combination (Cronbach's alpha=0.916, correlation=0.953). This differed from patient preferences, with items 3 ("Really listening") and 8 receiving the highest proportion of votes (19% and 17%, respectively). Preferences also varied by age, deprivation level, and consultation complexity. The most popular two-item combination (items 3 and 8) was selected by 10% of respondents, with 90% selecting other combinations.

CONCLUSION: The psychometrically optimal two-item combination did not align with patient preferences. Given variation in patient preferences and low agreement, reducing the CARE Measure to two-items may be inadvisable.}, } @article {pmid40902435, year = {2025}, author = {Midya, V and Bello, G and Andrew, AS and Re, DB and Stommel, EW and Arora, M}, title = {Dysregulation of hair-strand-based elemental biodynamics in amyotrophic lateral sclerosis.}, journal = {EBioMedicine}, volume = {119}, number = {}, pages = {105907}, doi = {10.1016/j.ebiom.2025.105907}, pmid = {40902435}, issn = {2352-3964}, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a rare motor neurodegenerative disorder and is predominantly diagnosed in older adults. Altered levels of essential and toxic elements have been implicated in ALS pathophysiology; however, little is known about the longitudinal biodynamic patterns of these elements in patients with ALS.

METHODS: Using a single individual hair strand, we generated time series data of 400-800 time points approximately at 2 to 4 hourly resolution on 17 elemental intensities in ALS-positive cases and ALS-negative controls from a national collection and a regional centre in the US (on a total sample of 391, with 295 cases and 96 controls, with median age at hair collection over 60 years). The elements included were Li, Mg, P, S, Ca, Cr, Mn, Fe, Co, Ni, Cu, Zn, As, Sr, Sn, Ba, and Pb. We analysed the growth increments in single hair strands using laser ablation-inductively coupled plasma-mass spectrometry to create time-resolved signals of elemental exposure and intensity along the hair strand. Two complementary information-theoretic methods, cross-recurrence quantification analysis and transfer entropy-based network analysis, were employed to generate time-resolved features that quantify the synchronisation of multi-element biodynamics.

FINDINGS: Male ALS-positive cases had significantly lower synchronicity in Cu-Zn temporal biodynamics than ALS-negative controls (recurrence: log(β) = -1.64, p-value < 0.001, q-value = 0.03). Female ALS-positive cases had lower synchronicity in Cr-Ni temporal biodynamics than ALS-negative controls (recurrence: log(β) = -1.59, p-value < 0.001, q-value = 0.46). In both males and females, multiple centrality measures of Cu (that quantify the importance of Cu within a network of all elemental intensities) were significantly lower in ALS-positive cases than in ALS-negative controls [in males, closeness centrality of Cu: log(β) = -0.64, p-value = 0.002, q-value = 0.04; in females, eigenvector centrality of Cu: log(β) = -0.53, p-value = 0.02, q-value = 0.97].

INTERPRETATION: We demonstrate that ALS-positive cases have significantly higher odds of collapse in the synchronisation of elemental biodynamics and worse connectedness in copper-based networks compared to ALS-negative controls.

FUNDING: US National Institutes of Health (P30ES023515, R01ES026033, U2CES030859, U2CES026561, R35ES030435, UL1TR004419, 1OT2NS136938-01, 1R01ES034133-01) and CDC/ATSDR (R01TS000331, R01TS000324 and R01TS000285).}, } @article {pmid40901987, year = {2025}, author = {Sun, Z and Li, C and Leitner, D and Wu, M and Zhang, J and Wisniewski, T and Ge, Y}, title = {Age-related Vascular Alterations in the Choroid Plexus: Novel Insights from Pathophysiology and Imaging Studies.}, journal = {Aging and disease}, volume = {}, number = {}, pages = {}, doi = {10.14336/AD.2025.0735}, pmid = {40901987}, issn = {2152-5250}, abstract = {The choroid plexus (ChP), a highly vascularized brain structure responsible for cerebrospinal fluid (CSF) production, undergoes significant age-related changes that may contribute to neurodegenerative diseases involving disrupted immune regulation, fluid homeostasis and waste clearance. Compared to other brain regions, vascular research on the ChP remains limited despite its critical role as a central interface between the blood and CSF. This review focuses on age-related vascular and structural alterations in the ChP from both histopathological and neuroimaging perspectives, and explores their impact on CSF dynamics, immune regulation, and the integrity of the blood-CSF barrier (BCSFB). Rather than shrinking, the aging ChP often enlarges due to dystrophic changes, as shown in volumetric MRI studies. Histological studies reveal epithelial degeneration, basement membrane thickening, and stromal fibrosis in the normal aging process. In dementia such as Alzheimer's disease (AD), proteomic studies have identified upregulation of AD- and immune-related proteins, along with downregulation of proteins linked to CSF clearance and metabolic support. Emerging high-resolution contrast-enhanced MRI techniques now allow in vivo visualization of microvascular changes within the ChP, shedding light on its normal and abnormal aging processes. Understanding these alterations is critical, as they may influence the onset and progression of various neurological diseases such as AD, Parkinson's disease (PD), normal pressure hydrocephalus, and amyotrophic lateral sclerosis (ALS). The recent advancements and challenges described in this study underscore the need for deeper investigation into ChP aging to inform future diagnostic and therapeutic strategies of neurodegenerative diseases.}, } @article {pmid40901879, year = {2025}, author = {Sun, G and Li, X and Hu, J and Yang, T and Liu, C and Wang, Z and Li, D and Xu, W}, title = {De novo design of protein binders to stabilize monomeric TDP-43 and inhibit its pathological aggregation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {122}, number = {36}, pages = {e2505320122}, doi = {10.1073/pnas.2505320122}, pmid = {40901879}, issn = {1091-6490}, support = {2020YFA0909200//MOST | National Key Research and Development Program of China (NKPs)/ ; 32101181//MOST | National Natural Science Foundation of China (NSFC)/ ; 32494764//MOST | National Natural Science Foundation of China (NSFC)/ ; 92353302//MOST | National Natural Science Foundation of China (NSFC)/ ; 32170683//MOST | National Natural Science Foundation of China (NSFC)/ ; 82188101//MOST | National Natural Science Foundation of China (NSFC)/ ; 22425704//MOST | National Natural Science Foundation of China (NSFC)/ ; 22JC1410400//Science and Technology Commission of Shanghai Municipality (STCSM)/ ; JCYJ-SHFY-2022-005//Chinese Academy of Sciences, Shanghai Branch (ä¸ç§'院上海分院)/ ; }, mesh = {*DNA-Binding Proteins/metabolism/chemistry/genetics ; Humans ; *Protein Aggregation, Pathological/metabolism ; Protein Aggregates ; Protein Binding ; Amyotrophic Lateral Sclerosis/metabolism/genetics ; Amyloid/metabolism/chemistry ; Frontotemporal Lobar Degeneration/metabolism ; Protein Stability ; }, abstract = {Pathological aggregation of transactive response DNA binding protein of 43 kDa (TDP-43), primarily driven by its low-complexity domain, is closely associated with various neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Despite the therapeutic potential of preventing TDP-43 aggregation, no effective small molecule or biomacromolecule therapeutics have been successfully developed so far. Here, we introduce a protein design strategy that yields de novo designed proteins capable of stabilizing the key amyloidogenic region of TDP-43 in its native helical conformation with nanomolar binding affinity. The binding mechanism was further characterized by the NMR and mutagenesis study. More importantly, we demonstrated that our designed protein binders efficiently reduced TDP-43 amyloid aggregation both in vitro and in cells. Our work provides a strategy for designing protein stabilizer of the native conformation of pathological proteins for preventing its amyloid aggregation, shedding light on the development of potential therapeutic approaches for ALS, FTLD, and other protein aggregation-associated diseases.}, } @article {pmid40901491, year = {2025}, author = {Igarashi, K and Ohue, M}, title = {Protein-ligand affinity prediction via Jensen-Shannon divergence of molecular dynamics simulation trajectories.}, journal = {Biophysics and physicobiology}, volume = {22}, number = {3}, pages = {e220015}, doi = {10.2142/biophysico.bppb-v22.0015}, pmid = {40901491}, issn = {2189-4779}, abstract = {Predicting the binding affinity between proteins and ligands is a critical task in drug discovery. Although various computational methods have been proposed to estimate ligand target affinity, the method of Yasuda et al. (2022) ranks affinities based on the dynamic behavior obtained from molecular dynamics (MD) simulations without requiring structural similarity among ligand substituents. Thus, its applicability is broader than that of relative binding free energy calculations. However, their approach suffers from high computational costs due to the extensive simulation time and the deep learning computations needed for each ligand pair. Moreover, in the absence of experimental ΔG values (oracle), the sign of the correlation can be misinterpreted. In this study, we present an alternative approach inspired by Yasuda et al.'s method, offering an alternative perspective by replacing the distance metric and reducing computational cost. Our contributions are threefold: (1) By introducing the Jensen-Shannon (JS) divergence, we eliminate the need for deep learning-based similarity estimation, thereby significantly reducing computation time; (2) We demonstrate that production run simulation times can be halved while maintaining comparable accuracy; and (3) We propose a method to predict the sign of the correlation between the first principal component (PC1) and ΔG by using coarse ΔG estimations obtained via AutoDock Vina.}, } @article {pmid40901333, year = {2025}, author = {Agrawal, H and Gupta, N}, title = {Deep learning models for pathological classification and staging of oesophageal cancer.}, journal = {World journal of clinical oncology}, volume = {16}, number = {8}, pages = {109893}, doi = {10.5306/wjco.v16.i8.109893}, pmid = {40901333}, issn = {2218-4333}, abstract = {This letter comments on Wei et al's study applying the Wave-Vision Transformer for oesophageal cancer classification. Highlighting its superior accuracy and efficiency, we discuss its potential clinical impact, limitations in dataset diversity, and the need for explainable artificial intelligence to enhance adoption in pathology and personalized treatment.}, } @article {pmid40901171, year = {2025}, author = {Budha, B and Chapagain, A and Adhikari, D and Bajracharya, S and Poudel, D and Budha, R and Adhikari, S and Gurmaita, RK}, title = {Acquired hemophilia a in a female with minimal change disease and hypothyroidism: a rare case report.}, journal = {Annals of medicine and surgery (2012)}, volume = {87}, number = {9}, pages = {6168-6172}, doi = {10.1097/MS9.0000000000003645}, pmid = {40901171}, issn = {2049-0801}, abstract = {INTRODUCTION: Juvenile amyotrophic lateral sclerosis (J-ALS) is extremely rare neurodegenerative motor neuron disorder that begins in early childhood or adolescence, before the age of 25 years old. It is characterized by gradual disease progression with comparison to adult-onset ALS and is often linked to genetic mutations.

CASE PRESENTATION: A 16-years-old female presented with long history of generalized weakness since age of 10 years, followed by bilateral sensorineural hearing loss, bulbar symptoms, and limb spasticity. Neurological examination revealed upper motor neuron signs in upper limbs, lower motor neuron signs in lower limbs, and bulbar involvement. Nerve conduction test was normal however, MRI showed early degenerative changes, and diagnosed with J-ALS after careful evaluation. She was started on Riluzole. Despite ICU care and supportive interventions including PEG and tracheostomy, she succumbed to respiratory failure.

DISCUSSION: Rarity, atypical presentation, and finical constraints can delay diagnosis of J-ALS. However, early diagnosis after careful evaluation of clinical symptoms, medical history, electrophysiological and imaging studies followed by prompt treatment with Riluzole and supportive interventions can help prolong survival and improve quality of life.

CONCLUSION: J-ALS is a rare motor neuron disease which possess immense diagnostic challenges, can exhibit relentless progression over short period of time with time.}, } @article {pmid40901053, year = {2025}, author = {Satapathy, P and Mehta, R and Sah, R}, title = {Comment on "Clinical Significance of Biochemical Pregnancy Loss in Recurrent Pregnancy Loss Patients: Insights From Euploid Embryo Transfers Minimizing Embryonic Bias".}, journal = {Reproductive medicine and biology}, volume = {24}, number = {1}, pages = {e12674}, doi = {10.1002/rmb2.12674}, pmid = {40901053}, issn = {1445-5781}, abstract = {This commentary addresses Kuwabara et al.'s study on biochemical pregnancy loss (BPL) in recurrent pregnancy loss (RPL) patients following euploid embryo transfers. While their methodology minimizes embryonic bias and strengthens maternal factor assessment, concerns regarding statistical interpretation and potential ascertainment bias limit generalizability. Nonetheless, this study raises important questions regarding the incorporation of BPL into RPL diagnostic frameworks.}, } @article {pmid40900744, year = {2025}, author = {Mani, S and Wasnik, S and Shandilya, C and Srivastava, V and Khan, S and Singh, KK}, title = {Pathogenic synergy: dysfunctional mitochondria and neuroinflammation in neurodegenerative diseases associated with aging.}, journal = {Frontiers in aging}, volume = {6}, number = {}, pages = {1615764}, pmid = {40900744}, issn = {2673-6217}, abstract = {The term "neurodegenerative diseases" (NDDs) refers to a range of aging-associated conditions, including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. Unique clinical symptoms and underlying pathological mechanisms distinguish each of these illnesses. Although these conditions vary, they share chronic neuroinflammation as a defining characteristic. Protein aggregation and mitochondrial dysfunction are believed to play a role in initiating the neuroinflammatory response and, subsequently, the development and course of these illnesses. Apart from providing energy to the cells, mitochondria are involved in the immunoinflammatory response associated with neurological disorders such as Alzheimer's disease, Parkinson's disease, multiple sclerosis, and epilepsy. This involvement is attributed to controlling processes such as inflammasome activation and cell death. Under inflammatory conditions, the underlying regulatory mechanisms for these aging-associated disorders may include calcium homeostasis imbalance, mitochondrial oxidative stress, mitochondrial dynamics, and epigenetics. Various NDDs are linked to neuroinflammation and mitochondrial dysfunction. The linkages between these occurrences are becoming more apparent, but the etiology of these pathologic lesions is yet to be elucidated. This review examines the role of neuroinflammation and mitochondrial dysfunction in the growth and course of NDDs, emphasizing the possibility of identifying novel therapeutic targets to address aging-related neurodegenerative processes and retard the progression of these illnesses.}, } @article {pmid40900615, year = {2025}, author = {Lee, Y and Park, MJ}, title = {Response to Li et al.'s Letter to the Editor Regarding "Do Skin Prick Tests Predict Nasal Provocation Test Outcomes in Allergic Rhinitis Patients?".}, journal = {International forum of allergy & rhinology}, volume = {}, number = {}, pages = {}, doi = {10.1002/alr.70029}, pmid = {40900615}, issn = {2042-6984}, } @article {pmid40899661, year = {2025}, author = {Atici Endes, E and Sherratt, JA and Gerisch, A}, title = {The Effect of Cell Adhesion on the Interpretation of Scratch Assay Data: A Non-Local Model.}, journal = {Mathematical medicine and biology : a journal of the IMA}, volume = {}, number = {}, pages = {}, doi = {10.1093/imammb/dqaf010}, pmid = {40899661}, issn = {1477-8602}, abstract = {Scratch assays are affordable methods developed for sampling wound healing in a laboratory setting. Thanks to these assays, it is possible to investigate the dynamical structure of cell migration and proliferation, which play a central role in the healing process of the wound. Johnston et al. (BMC Systems Biology 9:38, 2015) use scratch assay data to estimate migration and proliferation parameters in a Fisher-type model. The present study is a new attempt to interpret the same data using a non-local continuum approach that incorporates cell-cell adhesion. The non-local part of our model includes two different force functions representing different types of cell adhesion. Using these functions, we estimate the parameters involved in the diffusive and adhesive motion. The original and our model give similarly good agreement with the experimental data for their respective (optimal) parameter sets but the estimated diffusion coefficients differ significantly between both sets. Consequently, Johnston et al.'s data, and thus their experimental methodology are incapable of providing guidance on the effect of cell-cell adhesion in wound healing.}, } @article {pmid40898684, year = {2025}, author = {Zhu, Y and Bai, J and Wang, H and Li, M and Yang, F and Pang, X and Du, R and Zhao, J and Huang, X and Cui, F}, title = {The difference between cystatin C- and creatinine-based estimated glomerular filtration rate and survival in amyotrophic lateral sclerosis: a population-based cohort study.}, journal = {Neurodegenerative disease management}, volume = {}, number = {}, pages = {1-9}, doi = {10.1080/17582024.2025.2554224}, pmid = {40898684}, issn = {1758-2032}, abstract = {OBJECTIVES: We investigated the relationship between cystatin C- and creatinine-based estimated glomerular filtration rate (eGFRdiff) and amyotrophic lateral sclerosis (ALS) outcomes.

METHODS: We enrolled ALS patients diagnosed between January 2014 and December 2019. Experienced neurologists followed up the participants until January 2022. Absolute difference between eGFR (eGFRabdiff) and relative difference between eGFR (eGFRrediff) were obtained. Cox proportional hazard models were used to evaluate the relationship between eGFRdiff and ALS survival.

RESULTS: Negative eGFRabdiff were common in the patients (74.7%). For each SD increase of eGFRabdiff, the risk of poor prognosis for ALS patients decreased by 1.9% (HR, 0.981; 95% CI, 0.973-0.989). For each 10% increment in eGFRrediff, the risk of poor prognosis for ALS patients decreased by 17.7% (HR, 0.823; 95% CI, 754-0.898).

CONCLUSIONS: We found that large eGFRdiff was associated with poor prognosis in ALS. Monitoring eGFRdiff in ALS population facilitates prognostic stratification assessment and precise management.}, } @article {pmid40898457, year = {2025}, author = {Peng, S and Ouyang, J and Liu, Y and Wang, L and Liu, R}, title = {Causal effect of infectious mononucleosis on neurodegenerative diseases: A Mendelian randomization study.}, journal = {Medicine}, volume = {104}, number = {35}, pages = {e44145}, doi = {10.1097/MD.0000000000044145}, pmid = {40898457}, issn = {1536-5964}, support = {2019YFE0117100//the National key research and development program of China/ ; 82104603//the National Natural Science Foundation of China/ ; 82074174//the National Natural Science Foundation of China/ ; }, mesh = {Humans ; *Infectious Mononucleosis/complications/genetics/epidemiology/virology ; Mendelian Randomization Analysis ; *Neurodegenerative Diseases/genetics/virology/etiology/epidemiology ; Genome-Wide Association Study ; Polymorphism, Single Nucleotide ; Alzheimer Disease/genetics ; Parkinson Disease/genetics ; Multiple Sclerosis/genetics ; }, abstract = {Neurodegenerative diseases (NDs) are common chronic diseases with unknown etiology, and the association between virus and its pathogenesis is not clear. The aim of this study is to explore the role of virus in the pathogenesis of NDs by analyzing the causal effect between infectious mononucleosis (IM) mainly caused by Epstein-Barr virus and NDs. Based on the summary statistics of a large-scale genome-wide association study, we analyzed the causal effects of IM and NDs by Mendelian randomization (MR) using genetic variants as instrumental variables, including Alzheimer disease, Parkinson disease, amyotrophic lateral sclerosis, and multiple sclerosis. The reliability and stability of the MR analysis results were assessed by the MR-Egger intercept test, MR-PRESSO test, and heterogeneity test. Twenty-two single nucleotide polymorphisms that were significantly and strongly associated with IM were used as instrumental variables in the MR analysis. Inverse variance weighted as the main method of MR analysis shows that there were significant causal effects between IM and Alzheimer disease (OR: 1.037, 95% CI: 1.006-1.070) and Parkinson disease (OR: 0.964, 95% CI: 0.930-1.000), while IM was not significantly associated with amyotrophic lateral sclerosis (P = .269) and multiple sclerosis (P = .182). Sensitivity analyses showed that the results were robust. This study suggests that EB virus may contribute to the pathogenesis of NDs, and more research is needed to explore the specific mechanism of virus action on NDs.}, } @article {pmid40898454, year = {2025}, author = {Alharthi, S and Jafri, SA and Alzaedi, MA and Aljaed, NM and Eldoskey, MM and Abosabie, SAS and Oshi, M and Abosabie, SA and Kamal, NM}, title = {Multisystem inflammatory syndrome in children (MIS-C) presenting with valvulitis, myocarditis, and QTc prolongation: A case report from Saudi Arabia.}, journal = {Medicine}, volume = {104}, number = {35}, pages = {e43995}, doi = {10.1097/MD.0000000000043995}, pmid = {40898454}, issn = {1536-5964}, mesh = {Humans ; Female ; Child ; *COVID-19/complications/diagnosis/therapy ; *Myocarditis/etiology/diagnosis ; Saudi Arabia ; *Systemic Inflammatory Response Syndrome/diagnosis/complications/therapy ; *Long QT Syndrome/etiology/diagnosis ; Electrocardiography ; Diagnosis, Differential ; SARS-CoV-2 ; Echocardiography ; }, abstract = {RATIONALE: This case report highlights the complex clinical course and successful multidisciplinary management of a pediatric patient with multisystem inflammatory syndrome in children (MIS-C), who posed clinical dilemma at presentation. It underscores the ongoing clinical relevance of MIS-C as a post-Coronavirus disease 2019 sequelae and emphasizes the importance of maintaining a high index of suspicion for MIS-C in pediatric differential diagnoses, especially when symptoms overlap with other common conditions.

PATIENT CONCERNS: An 11-year-old previously healthy Saudi girl presented with gastrointestinal symptoms initially suggestive of acute appendicitis. Her condition rapidly deteriorated with signs of cardiovascular compromise.

DIAGNOSES: Surgical exploration confirmed a perforated appendix. Cardiac workup revealed elevated troponin levels, corrected QT interval prolongation (500 ms), ST-segment changes, and echocardiographic evidence of mitral and aortic regurgitation with reduced ejection fraction, leading to a diagnosis of MIS-C fulfilling both Centers for Disease Control and Prevention and World Health Organization criteria. Schwartz et al's criteria are widely accepted for diagnosing long QT syndrome, which guided our interpretation of the corrected QT interval prolongation observed in this case. According to the Centers for Disease Control and Prevention, MIS-C is defined by a constellation of symptoms occurring in individuals under 21 years with recent severe acute respiratory syndrome coronavirus 2 infection or exposure.

INTERVENTIONS: Management included intravenous immunoglobulin, corticosteroids, inotropes, diuretics, aspirin, and broad-spectrum antibiotics, coordinated by a multidisciplinary care team.

OUTCOMES: The patient experienced full cardiac recovery, confirmed through serial electrocardiogram and echocardiography over 1 year.

LESSONS: This case underscores the importance of recognizing MIS-C in children presenting with atypical symptoms such as abdominal pain. Timely diagnosis and early multidisciplinary intervention are essential to prevent serious cardiac complications.}, } @article {pmid40898372, year = {2025}, author = {Augur, ZM and Fogo, GM and Arbery, MR and Stern, AM and Benoit, CR and Hsieh, YC and Young-Pearse, TL}, title = {Optineurin deficiency disrupts phosphorylated tau proteostasis and clusterin expression in human neurons.}, journal = {Acta neuropathologica communications}, volume = {13}, number = {1}, pages = {188}, pmid = {40898372}, issn = {2051-5960}, support = {F31AG082393-03//NIA Ruth L. Kirschstein Predoctoral Individual National Research Service Award/ ; K00AG079793//NIA Pathway to Independence Award/ ; R01AG055909//NIH Grant/ ; }, mesh = {Humans ; *Neurons/metabolism/pathology ; *Membrane Transport Proteins/deficiency ; *Cell Cycle Proteins/deficiency ; *tau Proteins/metabolism ; *Alzheimer Disease/metabolism/pathology/genetics ; *Clusterin/metabolism ; Induced Pluripotent Stem Cells/metabolism ; *Proteostasis/physiology ; Phosphorylation ; *Transcription Factor TFIIIA/deficiency/genetics ; Female ; Autophagy ; Male ; Brain/metabolism/pathology ; Astrocytes/metabolism ; Aged ; }, abstract = {Optineurin (OPTN) is an autophagy adaptor protein involved in selective autophagy, including aggrephagy and mitophagy. Pathogenic mutations in OPTN have also been linked to amyotrophic lateral sclerosis, frontotemporal dementia, and glaucoma, supporting its role in the etiology of neurodegenerative diseases. Despite its established biological roles, knowledge about its potential contribution to Alzheimer's disease (AD) pathology and neuronal functioning is lacking. AD is characterized by the accumulation of extracellular amyloid-β plaques and intracellular phosphorylated tau (pTau) tangles, with dysfunction in the autophagy-lysosomal pathway exacerbating tau pathology and impairing proteostasis. To investigate the role of OPTN in neuronal proteostasis and AD, we utilized induced pluripotent stem cell-derived neuron (iN) and astrocyte (iA) models. Analyses revealed a significant negative correlation between OPTN and specific pTau epitopes in neurons, as well as a decrease in OPTN protein abundance in brain tissues of individuals with AD. Given these findings, we generated OPTN knockout (KO), heterozygous, and wildtype iNs and iAs using CRISPR/Cas9 editing of iPSCs in two genetic backgrounds. Loss of OPTN in iNs increased specific pTau proteoforms without substantially affecting autophagy processes or mitochondrial respiration. Despite no clear effect on mitochondrial function, several mitochondrial proteins, including OXCT1, were enriched in an unbiased analysis of the OPTN interactome in iNs, as well as proteins involved in intracellular trafficking. Proteomic analyses further identified intracellular clusterin, an AD risk gene, as significantly upregulated in OPTN KO iNs, suggesting OPTN may influence its intracellular processing. Our model system demonstrates modest roles for OPTN in certain neuronal biological processes and potential implications for AD pathogenesis. These findings also suggest that OPTN may exhibit functional redundancy with other autophagy adaptor proteins in human neurons, leading to relatively mild phenotypic changes with complete loss of OPTN.}, } @article {pmid40898360, year = {2025}, author = {Scholl, LS and Demleitner, AF and Riedel, J and Adachi, S and Neuenroth, L and Meijs, C and Tzeplaeff, L and Caldi Gomes, L and Galhoz, A and Cordts, I and Lenz, C and Menden, M and Lingor, P}, title = {Identification and validation of a tear fluid-derived protein biomarker signature in patients with amyotrophic lateral sclerosis.}, journal = {Acta neuropathologica communications}, volume = {13}, number = {1}, pages = {187}, pmid = {40898360}, issn = {2051-5960}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism/diagnosis ; Male ; Female ; Middle Aged ; Biomarkers/metabolism ; Aged ; *Tears/metabolism ; Adult ; Machine Learning ; Cohort Studies ; Proteomics ; *Eye Proteins/metabolism ; }, abstract = {The diagnosis of Amyotrophic Lateral Sclerosis (ALS) remains challenging, particularly in early stages, where characteristic symptoms may be subtle and nonspecific. The development of disease-specific and clinically validated biomarkers is crucial to optimize diagnosis. Here, we explored tear fluid (TF) as a promising ALS biomarker source, given its accessibility, anatomical proximity to the brainstem as an important site of neurodegeneration, and proven discriminative power in other neurodegenerative diseases. Using a discovery approach, we profiled protein abundance in TF of ALS patients (n = 49) and controls (n = 54) via data-independent acquisition mass spectrometry. Biostatistical analysis and machine learning identified differential protein abundance and pathways in ALS, leading to a protein signature. These proteins were validated by Western blot in an independent cohort (ALS n = 51; controls n = 52), and their discriminatory performance was assessed in-silico employing machine learning. 876 proteins were consistently detected in TF, with 106 differentially abundant in ALS. A six-protein signature, including CRYM, PFKL, CAPZA2, ALDH16A1, SERPINC1, and HP, exhibited discriminatory potential. We replicated significant differences of SERPINC1 and HP levels between ALS and controls across the cohorts, and their combination yielded the best in-silico performance. Overall, this investigation of TF proteomics in ALS and controls revealed dysregulated proteins and pathways, highlighting inflammation as a key disease feature, strengthening the potential of TF as a source for biomarker discovery.}, } @article {pmid40897992, year = {2025}, author = {Quigley, SE and Quigg, KH and Goutman, SA}, title = {Genetic and Mechanistic Insights Inform Amyotrophic Lateral Sclerosis Treatment and Symptomatic Management: Current and Emerging Therapeutics and Clinical Trial Design Considerations.}, journal = {CNS drugs}, volume = {}, number = {}, pages = {}, pmid = {40897992}, issn = {1179-1934}, support = {R01NS120926/NH/NIH HHS/United States ; R01NS127188/NH/NIH HHS/United States ; R01TS000344/ACL/ACL HHS/United States ; R01TS000327//Centers for Disease Control and Prevention/Agency for Toxic Substances and Disease Registry/ ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder affecting both upper and lower motor neurons. ALS is classically characterized by painless progressive weakness, causing impaired function of limbs, speech, swallowing, and respiratory function. The disease is fatal within 2-4 years, often the result of respiratory failure. The pathologic hallmark for a majority of ALS cases is aberrant cytoplasmic accumulations of the nuclear protein TAR-DNA binding protein (TDP-43). A total of 10-15% of ALS can be attributed to a single gene mutation, known as genetic or "familial" ALS, while the remainder of cases are termed nongenetic or "sporadic" although heritability has been measured in up to 37% in this population. Complex interactions between genetics, environment, and physiologic susceptibility are thought to contribute to disease. Management is primarily supportive in nature, though there are several approved treatments worldwide. This review details the mechanisms and evidence of approved disease-modifying treatments, relevant measures to track disease burden and progression used in clinical trials, and approaches to pharmacologic management of common symptoms in ALS. As there is not currently a cure for ALS, research into the complex pathophysiologic and genetic alterations contributing to disease is of great interest. This review further discusses the current understanding of genetic etiologies and altered physiology leading to disease, such as neuroinflammation, integrated stress response, aberrant proteostasis and mitochondrial dysfunction, among others. The translation of preclinical discoveries into current investigational therapeutics, novel therapeutic categories such as antisense oligonucleotides and stem cell transplantation, as well as future horizons harnessing the power of artificial intelligence in drug development and clinical trials are discussed.}, } @article {pmid40897843, year = {2025}, author = {Lai, Q and Zhang, X and Jiang, S and Krzyaniak, MD and Alayoglu, S and Agarwal, A and Liu, Y and Edenfield, WC and Kobayashi, T and Wang, Y and Dravid, V and Wasielewski, MR and Miller, JT and Kratish, Y and Marks, TJ}, title = {Stable single-site organonickel catalyst preferentially hydrogenolyses branched polyolefin C-C bonds.}, journal = {Nature chemistry}, volume = {}, number = {}, pages = {}, pmid = {40897843}, issn = {1755-4349}, support = {DOE DE-SC0024448//U.S. Department of Energy (DOE)/ ; DE-FG02-99ER14999//U.S. Department of Energy (DOE)/ ; DE-SC0001329//U.S. Department of Energy (DOE)/ ; DE-FG02-99ER14999//U.S. Department of Energy (DOE)/ ; DE-SC0012704//U.S. Department of Energy (DOE)/ ; NSF ECCS-2025633//National Science Foundation (NSF)/ ; NNA04CC36G//NASA | Ames Research Center/ ; }, abstract = {Current methods of processing accumulated polyolefin waste typically require harsh conditions, precious metals or high metal loadings to achieve appreciable activities. Here we examined supported, single-site organonickel catalysts for polyolefin upcycling. Chemisorption of Ni(COD)2 (COD, 1,5-cyclooctadiene) onto Brønsted acidic sulfated alumina (AlS) yields a highly electrophilic Ni(I) precatalyst, AlS/Ni(COD)2, which is converted under H2 to the active AlS/Ni[II]H catalyst. This single-site system exhibits unique hydrogenolysis selectivity that favours cleaving branched polyolefin C-C linkages, enabling the hydrogenolytic separation of polyethylene and isotactic polypropylene (iPP) mixtures. Moreover, AlS/Ni[II]H remains highly selective and active for hydrogenolysis of iPP admixed with polyvinyl chloride, and the spent catalyst can be repeatedly regenerated by AlEt3 treatment. Experimental mechanistic analysis and density functional theory modelling reveal a turnover-limiting C-C scission pathway featuring β-alkyl transfer and strong olefin binding. These results highlight the potential of nickel-based systems for the selective upcycling of complex plastic waste streams.}, } @article {pmid40896928, year = {2025}, author = {Issa, NP and Aydin, S and Goicoechea, EB and Carberry, N and Garret, MA and Smith, S and Habib, AA and Soliven, B and Rezania, K}, title = {Intermuscular coherence from muscle pairs in the leg as a biomarker for amyotrophic lateral sclerosis.}, journal = {Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology}, volume = {179}, number = {}, pages = {2110986}, doi = {10.1016/j.clinph.2025.2110986}, pmid = {40896928}, issn = {1872-8952}, abstract = {OBJECTIVE: To evaluate the diagnostic potential of intermuscular coherence (IMC) measured from leg muscle pairs as an early-stage biomarker for amyotrophic lateral sclerosis (ALS).

METHODS: Surface electromyography (sEMG) was recorded in neurotypical subjects and patients with early-stage ALS from muscle pairs: gastrocnemius lateralis-gastrocnemius medialis (GLGM), tibialis anterior-extensor digitorum brevis (TAED), and vastus lateralis-vastus medialis (VLVM). IMC within the 20-40 Hz range (IMCβγ) and the imaginary component of coherency in the 20-40 Hz range (ICOHβγ) were calculated. Area under the receiver operating characteristic curves (AUC) was used to assess diagnostic performance.

RESULTS: IMCβγ was lower in ALS patients than neurotypical subjects for all three muscle pairs (p < 0.05 in all cases). Diagnostic performance (AUC) ranged from 0.69 to 0.78 and was highest for TAED. Reducing the effect of volume conduction by using ICOHβγ tended to improve the diagnostic ability (AUC range 0.76 to 0.84).

CONCLUSIONS: IMCβγ from leg muscles, particularly TAED, can help differentiate early-stage ALS patients from neurotypical individuals. ICOHβγ further improves diagnostic performance by reducing volume conduction artifacts.

SIGNIFICANCE: Leg muscle IMC measurements could aid in the early and accurate diagnosis of ALS.}, } @article {pmid40896593, year = {2025}, author = {Ueno, Y and Nakamura, Y and Hata, T}, title = {The potential role of microRNA-mediated motor neuron-muscle pathologic interactions in amyotrophic lateral sclerosis.}, journal = {Molecular therapy. Nucleic acids}, volume = {36}, number = {3}, pages = {102675}, pmid = {40896593}, issn = {2162-2531}, } @article {pmid40895800, year = {2025}, author = {D'Arrigo, C and Labbate, S and Galante, D}, title = {Boosting the Therapeutic Potential of Extracellular Vesicles Derived From Mesenchymal Stem Cells via Advanced Preconditioning for Neurodegenerative Disorders.}, journal = {Stem cells international}, volume = {2025}, number = {}, pages = {2616653}, doi = {10.1155/sci/2616653}, pmid = {40895800}, issn = {1687-966X}, abstract = {Acute and chronic neurodegenerative conditions (NDs) are major causes of disability and mortality worldwide. Acute NDs encompass conditions such as stroke, traumatic brain injury (TBI), and spinal cord injury (SCI). On the other hand, chronic NDs include Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS). Currently, no definitive cure exists for these diseases, and available therapies focus primarily on slowing the progression of symptoms. Mesenchymal stem cells (MSCs), due to their multilineage differentiation capacity, immunomodulatory abilities, and regenerative properties, have gained attention in regenerative medicine. In recent years, extracellular vesicles (EVs) derived from MSCs have shown great promise as a cell-free therapeutic approach, eliminating the risks associated with direct MSCs use, such as tumorigenicity and poor cell survival after transplantation. EVs have emerged as powerful mediators of intercellular communication and tissue repair, exhibiting immunomodulatory, anti-inflammatory, and proregenerative properties. However, limitations such as low EVs yield and reduced efficacy due to MSCs replicative senescence restrict their therapeutic potential. Preconditioning strategies, including hypoxia, 3D cultures, and biochemical priming, have been explored in other fields to enhance EVs properties, yet their specific application to NDs remains under-reported. This review aims to address this gap by analyzing the preconditioning methods used to boost the therapeutic potential of MSCs-derived EVs for neurodegenerative diseases. These preconditioning strategies may enhance EVs yield, functional cargo, and targeted therapeutic efficacy for treating acute and chronic NDs.}, } @article {pmid40895324, year = {2025}, author = {Tan, X and Liu, G and Li, X and Zhong, F and Su, Z and Wang, H}, title = {Amyotrophic Lateral Sclerosis and Risk of Common Cancer: Mendelian Randomization Interrogation of Causality and Mediation.}, journal = {Phenomics (Cham, Switzerland)}, volume = {5}, number = {3}, pages = {270-283}, doi = {10.1007/s43657-024-00159-9}, pmid = {40895324}, issn = {2730-5848}, abstract = {UNLABELLED: Compared with the well-documented inverse comorbidity of common neurodegenerative diseases with some types of cancer, the association of amyotrophic lateral sclerosis (ALS) with cancer was obscure. This Mendelian randomization (MR) analysis was aimed to appraise the causal relationship of ALS with cancer. Leveraging summary statistics of genome-wide association study (GWAS) for ALS, overall-cancer and nine types of site-specific common solid cancer including colorectal cancer (CRC) in populations of European (discovery and replication) and East Asian ancestry, we investigated the causal association of ALS with cancer using inverse-variance weighted (IVW) method and complementary sensitivity analyses. We performed MR-based mediation analysis to assess possible role of serum lipid traits such as hyperlipidemia, one shared risk factor of ALS and CRC, in their causal association. We found that genetically-predicted ALS was not associated with overall-cancer and other tested types of cancer, but was causally associated with reduced risk of CRC [odds ratio (OR) 0.84; 95% confidence interval (95% CI) 0.74-0.96; p = 0.011, OR 0.32; 95% CI 0.15-0.69; p = 0.004, in datasets of European (discovery) and East Asian ancestry respectively]. We observed absences of directional pleiotropy (MR Egger, intercept = -0.02 and -0.02, p = 0.49 and 0.60), instrumental outlier (MR-PRESSO, p = 0.95 and 0.84) or heterogeneity (Cochran Q, p = 0.95 and 0.82). Null reverse causality of CRC with ALS was found in either datasets. However, we found no evidence of the inverse association of ALS with CRC in either the replication (OR 0.99; 95% CI 0.93-1.06) or the combined European datasets (OR 0.92; 95% CI 0.79-1.09). Mediation analysis in European datasets suggested that hyperlipidemia may affect the risk of CRC via ALS in an indirect manner, with the measured mediation effect of hyperlipidemia on CRC being -0.02 (95% CI -0.04 to -0.002, p = 0.03). Our two-sample MR study in trans-ethnic populations uncovered that genetically proxied ALS may be causally associated with reduced risk of CRC, providing new insight into the inverse comorbidity and etiological causality of neurodegenerative disease and cancer.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s43657-024-00159-9.}, } @article {pmid40894870, year = {2025}, author = {Manville, RW and Sidlow, R and Abbott, GW}, title = {Conifer metabolite pisiferic acid restores activity in human Kv1.2 potassium channels carrying pathogenic sequence variants.}, journal = {iScience}, volume = {28}, number = {9}, pages = {113283}, doi = {10.1016/j.isci.2025.113283}, pmid = {40894870}, issn = {2589-0042}, abstract = {Sequence variants in KCNA2, the gene encoding voltage-gated potassium channel Kv1.2, cause epilepsy, delayed cognitive development, and movement disorders. Drugs that directly correct mutant Kv1.2 function are lacking. Kv1.2 downregulation is also implicated in pain and amyotrophic lateral sclerosis (ALS). We recently found that the abietane diterpenoid pisiferic acid (PA) from conifer Chamaecyparis pisifera beneficially restores activity in pathogenic loss-of-function (LOF)-variant Kv1.1 channels. Here, using cellular electrophysiology, we classified 19 human Kv1.2 gene variants (pathogenic or of unknown significance) into LOF, gain of function (GOF), or mixed LOF/GOF. By hyperpolarizing their voltage dependence of activation, PA improved function in 13/13 LOF and 1/1 LOF/GOF pathogenic Kv1.2 variants tested, using cRNA ratios representative of autosomal dominant KCNA2 disorders. In silico docking, mutagenesis, and electrophysiology identified a PA binding site in the Kv1.2 voltage sensor. Given its in vitro efficacy and low preclinical toxicity, PA is a promising lead compound for Kv1.2 LOF disorders.}, } @article {pmid40894255, year = {2025}, author = {Hu, N and Chen, L and Hu, G and Ma, R}, title = {Advancements in extracellular vesicle therapy for neurodegenerative diseases.}, journal = {Exploration of neuroprotective therapy}, volume = {5}, number = {}, pages = {}, doi = {10.37349/ent.2025.1004104}, pmid = {40894255}, issn = {2769-6510}, abstract = {Neurodegenerative diseases represent a significant and growing challenge to public health worldwide. Current therapeutic strategies often fall short in halting or reversing disease progression, highlighting the urgent need for novel approaches. Extracellular vesicles (EVs) have garnered attention as potential therapeutic agents due to their role in intercellular communication and their ability to transport bioactive cargo, including proteins, nucleic acids, and lipids. This review provides a comprehensive overview of the biology of EVs, their involvement in neurodegenerative diseases, and the potential for EV-based therapies. We discuss the different types of EVs, their biogenesis, and their cargo composition, emphasizing their relevance to neurological processes such as protein misfolding, neuroinflammation, and oxidative stress. Preclinical studies investigating EVs as carriers of therapeutic cargo and their ability to promote neuronal survival and regeneration are examined, with a focus on evidence from animal models of neurodegenerative disorders. We explore the use of EVs in the treatment of neurodegenerative diseases, including ongoing clinical trials, methods for EV isolation and modification, and future perspectives on personalized EV-based therapies designed to meet the unique needs of individual patients. Overall, this review highlights the potential of EVs as a promising avenue for neurodegenerative disease therapy, while also addressing key research gaps and translational hurdles that need to be overcome for their successful clinical implementation.}, } @article {pmid40892373, year = {2025}, author = {Dietrich, J and Hollstein, A}, title = {Authors' response to Tiffet et al.'s comment on "Performance and Reproducibility of Large Language Models in Named Entity Recognition: Considerations for the Use in Controlled Environments".}, journal = {Drug safety}, volume = {}, number = {}, pages = {}, pmid = {40892373}, issn = {1179-1942}, } @article {pmid40891814, year = {2025}, author = {Ekaterina Slotina, DM and Ditscheid, DRNB and Meissner, DPF and Wiese, A and Hezel, J and Marschall Dipl Oec, DMU and Wedding, APDMU and Freytag, PDRPMA}, title = {Quality of Palliative Care in Nursing Homes and Community Care in Deceased with Chronic Obstructive Pulmonary Disease (COPD), Dementia, Amyotrophic Lateral Sclerosis (ALS), and Cancer: A Retrospective Analysis of Claims Data (2016-2019).}, journal = {Journal of palliative care}, volume = {}, number = {}, pages = {8258597251353315}, doi = {10.1177/08258597251353315}, pmid = {40891814}, issn = {2369-5293}, abstract = {ObjectivePalliative care is more commonly provided to patients with cancer than to those with non-oncological conditions. Little is known about the prevalence of inappropriate care and whether differences exist depending on the underlying disease. This study investigates the care during the last month of life in patients with cancer and non-oncological conditions, such as amyotrophic lateral sclerosis (ALS), chronic obstructive pulmonary disease (COPD), and dementia, considering the care setting (nursing home vs. community care).MethodsWe conducted a population-based, retrospective analysis of deceased in 2016-2019 with COPD (n = 4,036), dementia (n = 40,853), or ALS (n = 608). Logistic regression analyses compared the care quality with that of the deceased with cancer (n = 58,315). Interaction analyses examined setting effects. Outcome measures included validated quality indicators: hospital and intensive care unit (ICU) stays, emergency service utilization, and place of death.ResultsDeceased with COPD, dementia, and ALS more frequently utilized emergency services compared to those with cancer (40.4%, 28.4%, 29.0% vs. 24.4%, respectively, p < .05) and were less likely to die in a hospital (excluding palliative care units; 38.2%, 15.3%, 25.7% vs. 40.3%, respectively, p < .05). Differences were observed in ICU (13.6%, 3.4%, 6.1% vs. 4.3%, respectively, p < .05) and hospital admissions (42.7% for COPD vs. 31.5% for oncological patients, p < .001). The same pattern was observed across all conditions: deceased in community care had higher rates in all quality indicators than those in nursing homes.ConclusionsThe results suggest differences in care quality depending on the underlying disease. Nononcological patients in community care are less frequently and less adequately cared for than oncological patients.}, } @article {pmid40891578, year = {2025}, author = {Toyota, S}, title = {Expanding Chemistry of Expanded Helicenes.}, journal = {Chemistry (Weinheim an der Bergstrasse, Germany)}, volume = {}, number = {}, pages = {e02193}, doi = {10.1002/chem.202502193}, pmid = {40891578}, issn = {1521-3765}, support = {23K26637//Japan Society for the Promotion of Science/ ; 20H02721//Japan Society for the Promotion of Science/ ; 23H01944//Japan Society for the Promotion of Science/ ; }, abstract = {Expanded helicenes are interesting compounds created by modifying the original helicene structure through the incorporation of linearly fused benzene rings, enlarging the helical diameter. Motivated by Tilley et al.'s report of a key expanded helicene structure in 2017, several research groups have synthesized such nonplanar aromatic compounds, aiming to explore their impressive structures, properties, and chiroptical performance. This review highlights recent advances in the expanded helicene chemistry through experimental and theoretical studies. The shape and length of helical structures depend on the number and combination of angularly and linearly fused benzene rings. Helical structures are classified using notations, and specific compounds corresponding to each structural form, namely, hexagonal, triangular, rhombic, or others, are introduced herein. As an extension of the molecular design, examples of nonhexagonal and heteroaromatic ring-embedded expanded helicenes are presented. Specifically, this review focuses on how the diameters, lengths, and turn numbers of helical structures depend on dynamic processes involving helical inversion and chiroptical properties (circular dichroism (CD) and circularly polarized luminescence (CPL)). The characteristics and perspectives of this molecular design are also discussed.}, } @article {pmid40891506, year = {2025}, author = {Pir, GJ and Buddenkotte, J and Alam, MA and Own, A and Eck, RJ and Kraemer, BC and Mandelkow, E and Steinhoff, M}, title = {TDP-43 proteinopathies and neurodegeneration: insights from Caenorhabditis elegans models.}, journal = {The FEBS journal}, volume = {}, number = {}, pages = {}, doi = {10.1111/febs.70239}, pmid = {40891506}, issn = {1742-4658}, support = {11S-0117 180326//Qatar National Research Fund/ ; //Katharina Hardt Foundation/ ; F99AG088436/NH/NIH HHS/United States ; //Cure Alzheimer's Fund/ ; }, abstract = {TDP-linked proteinopathies, including amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD) and limbic-predominant age-related TDP-43 encephalopathy (LATE), are characterised by pathogenic deposits containing transactive response DNA-binding protein 43 (TDP-43) in the brain and spinal cord of patients. These hallmark pathological features are associated with widespread neuronal dysfunction and progressive neurodegeneration. TDP-43's role as an essential RNA/DNA-binding protein in RNA metabolism and gene expression regulation is clear, but deciphering the intricate pathophysiological mechanisms underpinning TDP-43-mediated neurodegeneration is paramount for developing effective therapies and novel diagnostic tools for early detection before frank neuronal loss occurs. The nematode Caenorhabditis elegans, with highly conserved TDP-43 orthologue TDP-1, serves as a powerful genetic model to investigate the molecular underpinnings of TDP-43 proteinopathies. Here, we provide a brief overview of the structural and functional characteristics of TDP-43 and TDP-1, highlighting their conserved roles in RNA metabolism, stress responses, and neurodegeneration. We then delve into the pathobiology of TDP-43, drawing insights from C. elegans models expressing either monogenic TDP-43 variants or bigenic combinations with ALS-associated risk genes, and discuss how these models have advanced our understanding of the pathomechanisms of TDP-43 proteinopathies. By employing its simplicity and genetic manipulability, we discuss how these models have helped identify chemical and genetic suppressors of TDP-43-induced phenotypes, including small molecules like Pimozide and the probiotic Lacticaseibacillus rhamnosus HA-114, now in clinical trials. This review underscores the translational value of C. elegans in unraveling the biochemical pathways and interactions in TDP-43 proteinopathies that perturb cellular physiology, potentially facilitating mechanism-based therapy development.}, } @article {pmid40891053, year = {2025}, author = {Bilican, S and Nabawi, Y and Zhang, WH and Petrovic, D and Wehrmann, M and Muñoz-García, S and Koyuncu, S and Vilchez, D}, title = {C9orf72 ALS-causing mutations lead to mislocalization and aggregation of nucleoporin Nup107 into stress granules.}, journal = {FEBS letters}, volume = {}, number = {}, pages = {}, doi = {10.1002/1873-3468.70156}, pmid = {40891053}, issn = {1873-3468}, support = {CRC1678 (project B06 to D.V)//Deutsche Forschungsgemeinschaft/ ; Germany's Excellence Strategy-CECAD (EXC2030-39390661388)//Deutsche Forschungsgemeinschaft/ ; Largeinstrument grant (INST216/1329-1 FUGG to CECAD Proteomics Facility)//Deutsche Forschungsgemeinschaft/ ; Research Unit FOR5762 (project VI742/10-1 to D.V)//Deutsche Forschungsgemeinschaft/ ; 2021-EKSE.95 to D.V//Else Kröner-Fresenius-Stiftung/ ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal disorder caused by motor neuron degeneration. Hexanucleotide repeat expansions in the C9orf72 gene, the most common genetic cause of ALS (C9-ALS), drive toxicity through different mechanisms. These pathological changes include alterations in stress granules (SGs), ribonucleoprotein complexes formed under stress conditions. Here, we show that G3BP1, a core component of SGs, exhibits enhanced interaction with the nucleoporin Nup107 in motor neurons derived from patient iPSCs carrying C9orf72 mutations. Moreover, Nup107 colocalizes with SGs and aggregates in C9-ALS motor neurons. Notably, knockdown of npp-5, the Caenorhabditis elegans ortholog of Nup107, alleviates ALS-associated phenotypes in worm models, including reduced lifespan and impaired motility. Together, our findings provide insights into disease-related changes in C9-ALS pathogenesis.}, } @article {pmid40891024, year = {2025}, author = {Pan, Y and Spiteri, AG and Runwal, P and Sun, J and Hutchinson, DS and Kagawa, Y and Turner, BJ and Huang, C and Shah, AD and Schittenhelm, RB and Nicolazzo, JA}, title = {Increased ATP production and P-glycoprotein activity underlie the marked changes in blood-brain barrier transport of drugs in a mouse model of amyotrophic lateral sclerosis.}, journal = {British journal of pharmacology}, volume = {}, number = {}, pages = {}, doi = {10.1111/bph.70147}, pmid = {40891024}, issn = {1476-5381}, support = {23AARF-1020292/ALZ/Alzheimer's Association/United States ; GNT2007912//National Health and Medical Research Council/ ; //FightMND/ ; }, abstract = {BACKGROUND AND PURPOSE: Patients with amyotrophic lateral sclerosis (ALS) are prescribed many medications for symptomatic relief. However, how potential alterations to the blood-brain barrier (BBB) affect the brain exposure of drugs in ALS remains under-investigated.

EXPERIMENTAL APPROACH: We used high-dimensional proteomic analysis, cellular metabolism, and mitochondrial functional assays to characterise isolated brain microvascular endothelial cells (BMECs) from wildtype and SOD1[G93A] transgenic mice, a mouse model of familial ALS, at a late-symptomatic age (P115-120), together with a transcardiac brain perfusion technique to assess BBB function in situ.

KEY RESULTS: The BBB of the SOD1[G93A] transgenic (TG) mice was significantly altered, including a 1.3-fold decrease in apparent brain microvascular volume, and decreased BBB transport of [3]H-diazepam (1.4-fold) and [3]H-2-deoxy-D-glucose (1.2-fold). BMEC proteomic analysis revealed multiple changes in TG mice including altered transmembrane activity, metabolism, and mitochondrial function, as revealed by gene set enrichment analysis, alongside altered glucose transporter (Glut1) abundance. These proteomic findings supported the identified increase in mitochondrial basal/ATP-linked respiration, mitochondrial action potential, ATP production, and intracellular ATP levels in SOD1[G93A] mouse BMECs. The BBB transport of [3]H-digoxin, a specific ATP-binding cassette efflux P-glycoprotein (P-gp) substrate, was reduced by 11.0% in SOD1[G93A] mice. This was confirmed by a 46.7% reduction in BMEC uptake of [3]H-digoxin, an observation that was reversed by resolving the hypermetabolic state of SOD1[G93A] BMECs.

CONCLUSION AND IMPLICATIONS: These findings open possible therapeutic avenues that could be exploited to overcome P-gp-mediated CNS drug resistance in ALS.}, } @article {pmid40888144, year = {2025}, author = {Hullock, K and O'Cathain, A and Sampson, F and Woodward, J and Coates, E and Stavroulakis, T and White, SM and White, D and Norman, P and McDermott, C}, title = {Optimising Calorie Intake for People With Amyotrophic Lateral Sclerosis: A Process Evaluation of a Complex Behaviour Change Intervention.}, journal = {Health expectations : an international journal of public participation in health care and health policy}, volume = {28}, number = {5}, pages = {e70417}, pmid = {40888144}, issn = {1369-7625}, support = {//This project is funded by the National Institute for Health Research (NIHR) Programme Grants for Applied Research Programme (Grant Reference Number RP-PG-1016-20006) and supported by the NIHR Sheffield Biomedical Research Centre./ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diet therapy/psychology ; Female ; Male ; *Energy Intake ; United Kingdom ; Middle Aged ; Aged ; Caregivers/psychology ; Process Assessment, Health Care ; Qualitative Research ; Adult ; }, abstract = {OBJECTIVE: To explore intervention fidelity and experiences of using a new intervention designed to optimise calorie intake in people with amyotrophic lateral sclerosis (ALS).

METHODS: A mixed-methods process evaluation was conducted alongside an ongoing randomised controlled trial across 15 ALS specialist centres in the United Kingdom. Data collection included 146 healthcare professional-completed fidelity checklists, audio recordings of 5 intervention sessions, and qualitative interviews with 32 healthcare professionals, patients and informal caregivers.

RESULTS: Intervention fidelity was high (88%: 1059/1204 items completed by healthcare professionals). Healthcare professionals, patients and informal caregivers within the sample recognised the intervention's value and engaged with it. Patients were motivated to use the intervention because they believed it could slow disease progression, and it gave them a sense of control. Despite challenges with the intervention, including patient concerns about weight gain and physical limitations in food preparation and consumption, patients in this sample remained committed to using the intervention. However, healthcare professionals suggested that these challenges may have negatively influenced trial recruitment and retention. Caregivers played a crucial role in supporting patients emotionally and physically, helping them to adhere to the intervention.

CONCLUSIONS: The intervention was feasible to implement and was delivered with fidelity. While patient engagement in this sample was strong, the intervention usability may be time-limited as physical function declines. Therefore, the intervention may be best suited for those with slower-progressing ALS who can manage the intervention and dietary changes. Moving forward, continued evaluation is needed to assess effectiveness and explore subgroup differences based on ALS type (slow vs. fast progressing).

PPIE CONTRIBUTION: PPI was integral to the process evaluation. PPI members reviewed key study documents, including the Participant Information Sheet and consent forms, leading to participant materials that were clear and easily understood. They also participated in developing the intervention.

TRIAL REGISTRATION: IRAS ID 275949, ISRCTN30588041.}, } @article {pmid40888932, year = {2025}, author = {Platikanov, S and Palomas, A and Mata, MC and Tauler, R and Villar, J and Bragós, R and Bermejo, S and Jaumot, J and Lacorte, S}, title = {Coupling electrochemical and spectroscopic methods for river water dissolved organic matter characterization.}, journal = {Environmental monitoring and assessment}, volume = {197}, number = {9}, pages = {1071}, pmid = {40888932}, issn = {1573-2959}, support = {TED2021-131552B-C21 and TED2021-131552B-C22//Ministerio de Ciencia e Innovación (MCIN) y la Agencia Estatal de Investigación (AEI) and the European Union 'Next Generation EU/PRTR/ ; }, mesh = {*Rivers/chemistry ; *Environmental Monitoring/methods ; *Water Pollutants, Chemical/analysis ; Electrochemical Techniques ; Spectrometry, Fluorescence ; Spectrum Analysis ; *Humic Substances/analysis ; Dielectric Spectroscopy ; }, abstract = {Monitoring dissolved organic matter (DOM) in surface waters is essential for assessing ecosystem health and detecting pollution. However, conventional spectroscopic techniques often provide limited information about the electrochemical behavior of DOM. This study integrates electrochemical impedance spectroscopy (EIS) with classical methods such as UV-Vis absorption and fluorescence spectroscopies to improve DOM characterization in river water samples. In particular, this coupling provides additional insights into the electrochemical properties of DOM, which are not captured by conventional spectroscopic techniques. This study combined multiple data sources, including physicochemical parameters (e.g., water temperature, pH, conductivity), EIS spectral scores, fluorescence indices, and DOM fractions resolved by multivariate curve resolution-alternating least squares (MCR-ALS) applied to excitation-emission matrix (EEM) fluorescence data. The results from these different methods were then merged into a single dataset for a global principal component analysis (PCA), which allowed us to identify shared patterns and correlations across methods. The results revealed that low-altitude rivers showed the highest DOM content, followed by mid-altitude rivers, while high-altitude rivers presented the lowest. The PCA model indicated that low-frequency regions in the EIS spectra correlated with higher DOM content, whereas mid- to high-frequency regions were associated with lower DOM levels. These frequency-dependent patterns reflected differences in charge transfer and dielectric behavior of DOM in the river samples, which are not accessible through optical techniques. This highlights the potential of EIS as a complementary tool that provides electrochemical information on DOM composition for better water quality assessment.}, } @article {pmid40888599, year = {2025}, author = {Mearelli, M and Hirschberg, I and Weissleder, C and Giachino, C and Pérez, MJ and Dubroux, M and Provenzano, F and Rizzuti, M and Ottoboni, L and Sheth, U and Gendron, TF and Corti, S and Deleidi, M}, title = {C9orf72 Repeat Expansion Induces Metabolic Dysfunction in Human iPSC-Derived Microglia and Modulates Glial-Neuronal Crosstalk.}, journal = {Glia}, volume = {}, number = {}, pages = {}, doi = {10.1002/glia.70080}, pmid = {40888599}, issn = {1098-1136}, support = {01GM1913//E-Rare3 INTEGRALS/ ; 101003329/ERC_/European Research Council/International ; 490761034//Deutsche Forschungsgemeinschaft/ ; 01ED2005B//EU Joint Programme - Neurodegenerative Disease Research/ ; }, abstract = {The C9orf72 hexanucleotide repeat expansion mutation is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia, but its cell type-specific effects on energy metabolism and immune pathways remain poorly understood. Using induced pluripotent stem cell (iPSC)-derived motor neurons, astrocytes, and microglia from C9orf72 patients and their isogenic controls, we investigated metabolic changes at the single-cell level under basal and inflammatory conditions. Our results showed that microglia are particularly susceptible to metabolic disturbances. While C9orf72 motor neurons exhibited impaired mitochondrial respiration and reduced ATP production, C9orf72 microglia presented pronounced increases in glycolytic activity and oxidative stress, accompanied by the upregulation of the expression of key metabolic enzymes. These metabolic changes in microglia were exacerbated by inflammatory stimuli. To investigate how these changes affect the broader cellular environment, we developed a human iPSC-derived triculture system comprising motor neurons, astrocytes, and microglia. This model revealed increased metabolic activity in all cell types and highlighted that microglia-driven metabolic reprogramming in astrocytes contributes to the vulnerability of motor neurons under inflammatory conditions. Our findings highlight the central role of microglia in driving metabolic dysregulation and intercellular crosstalk in ALS pathogenesis and suggest that targeting metabolic pathways in immune cells may provide new therapeutic avenues.}, } @article {pmid40887399, year = {2025}, author = {Wang, Y and Lin, J and Qu, Y and Ding, Y and Ye, Z and Zhu, Z and Chen, W and Chen, Z and Sun, H and Hu, F and Chen, C and Fang, L and Li, R and Zhang, B and Wang, N and Fu, Y and Chen, W and Zhang, Q and , }, title = {Corrigendum to "Biomarker profile of a Chinese ALS cohort: A comprehensive clinical-biomarkers-imaging analysis".}, journal = {Neurobiology of disease}, volume = {}, number = {}, pages = {107073}, doi = {10.1016/j.nbd.2025.107073}, pmid = {40887399}, issn = {1095-953X}, } @article {pmid40887165, year = {2025}, author = {Eising, J and Dissmeyer, N}, title = {Identification of arginylated N-termini with specific reagents.}, journal = {Methods in enzymology}, volume = {718}, number = {}, pages = {307-317}, doi = {10.1016/bs.mie.2025.06.024}, pmid = {40887165}, issn = {1557-7988}, mesh = {Humans ; *Protein Processing, Post-Translational ; *Arginine/metabolism/chemistry ; *Aminoacyltransferases/metabolism ; *Proteins/metabolism/chemistry ; Animals ; }, abstract = {N-terminal arginylation is a posttranslational modification of proteins that may determine their fate with respect to their stability and half-life and timing of their physiological and molecular function. Arginylated N-termini are in some documented cases N-degrons leading to degradation through the proteasome or autophagic-lysosomal system (ALS) regulating cellular homeostasis and global physiological alterations. Proteins that are targets of arginyl-transferases (Ates) capable of ligating arginine (Arg) residues to N-terminal amino groups and internal side chains show therefore high importance for manipulation in therapeutic and research contexts. Because of that, identifying those substrates is of high interest for all organisms from human to plant research. This chapter will shed some light onto methods for identification of arginylated N-termini with focus on specific antibodies targeting the N-terminally modified proteins.}, } @article {pmid40887101, year = {2025}, author = {Guillot, SJ and Luppi, PH and Dupuis, L and Bolborea, M}, title = {Sleep in neurodegenerative diseases: A focus on melatonin, melanin-concentrating hormone and orexin.}, journal = {Journal of neuroendocrinology}, volume = {}, number = {}, pages = {e70085}, doi = {10.1111/jne.70085}, pmid = {40887101}, issn = {1365-2826}, support = {ANR-16-CE16-0015//Agence Nationale de la Recherche/ ; ANR-16-CE92-0031//Agence Nationale de la Recherche/ ; ANR-19-CE17-0016//Agence Nationale de la Recherche/ ; ANR-20-CE17-0008//Agence Nationale de la Recherche/ ; ANR-24-CE37-4064//Agence Nationale de la Recherche/ ; //TargetALS/ ; //Fondation Thierry Latran/ ; //Association Francaise de Recherche sur la sclérose latérale amyotrophique/ ; //Radala Foundation for ALS Research/ ; //ARSLA/ ; //University of Starsbourg fundation/ ; //Fondation Bettencourt Schueller/ ; DEQ20180339179//Fondation pour la Recherche Médicale/ ; //Axa Research Funds/ ; }, abstract = {Sleep and circadian rest-activity rhythm alterations are recognised as inherent clinical features of various neurodegenerative diseases. Traditionally viewed as secondary manifestations of neurodegeneration, recent studies have revealed that disruptions in circadian rhythm and sleep-wake cycles can precede clinical symptoms and significantly contribute to the underlying pathophysiological progression. In this review, we summarise recent research on the impact of sleep and circadian rhythm alterations in ageing and major neurodegenerative diseases, including Alzheimer's, Parkinson's, Huntington's, amyotrophic lateral sclerosis, and frontotemporal dementia, highlighting the roles of melatonin, orexin, and melanin-concentrating hormone (MCH) systems as key regulators at the intersection of sleep and neurodegeneration. We argue that sleep and circadian alterations may serve as early biomarkers and therapeutic targets for these diseases.}, } @article {pmid40886845, year = {2025}, author = {Beraja, GE and Eber, AE and Yosipovitch, G}, title = {Response to Peng et al.'s "Efficacy and safety of 308-nanometer light-emitting diode phototherapy for Prurigo Nodularis: A randomized and self-controlled clinical trial.".}, journal = {Journal of the American Academy of Dermatology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jaad.2025.08.064}, pmid = {40886845}, issn = {1097-6787}, } @article {pmid40885478, year = {2025}, author = {Hafiz, B and Aldahlawi, A and Ashqar, A and Hamzah, A and Alotaibi, Y and Bajunaid, K and Baeesa, S}, title = {Outcomes of Surgical Versus Endovascular Treatment of Spinal Dural Arteriovenous Fistula: A Systematic Review and Meta-Analysis.}, journal = {World neurosurgery}, volume = {}, number = {}, pages = {124420}, doi = {10.1016/j.wneu.2025.124420}, pmid = {40885478}, issn = {1878-8769}, abstract = {BACKGROUND: Spinal dural arteriovenous fistulas (SDAVFs) are the most prevalent type of spinal vascular malformation and can lead to progressive neurological impairments if left untreated. Endovascular embolization and microsurgical resection are treatment options, although the optimal treatment method remains a subject of debate.

OBJECTIVE: A comprehensive systematic review and meta-analysis to compare the endovascular and microsurgical treatment outcomes of SDAVFs.

METHODS: An exhaustive literature search was conducted in the PubMed, Embase, Scopus, and Web of Science databases, encompassing publications from 2014 to 2024. A total of 522 patients from seven studies (417 surgical and 105 endovascular) met the inclusion criteria. Information on post-treatment complications, recurrence/failure rates, and functional improvement as assessed by the Aminoff-Logue Scale (ALS) or modified ALS (mALS) was extracted. I[2] statistics were used to evaluate heterogeneity, and random-effects models were used to compute risk ratios (RRs) and odds ratios (ORs).

RESULTS: Compared to endovascular intervention, surgical treatment was linked to significantly lower rates of recurrence or treatment failure (RR: 0.19; 95% CI: 0.09-0.39; p < 0.001), especially in long-term follow-up and thoracic-level studies. With greater ALS/mALS gains and a higher percentage of patients achieving full or partial recovery, functional improvement favored surgery. Although complication types varied, complication rates were similar across modalities (OR: 0.84; 95% CI: 0.48-1.49). Asymmetry in funnel plots indicated possible publication bias in favor of successful surgical outcomes.

CONCLUSION: For SDAVFs, surgical ligation provides better long-term results than endovascular embolization in terms of neurological recovery and recurrence prevention. Even though both procedures are usually safe, surgery is the recommended first-line course of action due to the higher failure and recurrence rates linked to embolization, especially in patients with operable anatomy and progressive symptoms.}, } @article {pmid40885336, year = {2025}, author = {Pavlović, MD}, title = {Response to Li et al.'s "Therapeutic efficacy of platelet-rich plasma combining with microneedling and topical minoxidil in refractory severe androgenic alopecia["].}, journal = {Journal of the American Academy of Dermatology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jaad.2025.05.1463}, pmid = {40885336}, issn = {1097-6787}, } @article {pmid40884740, year = {2025}, author = {Kalasa Anil Kumar, AP and Subair, S and Basthikoppa Shivamurthy, P and Ummar, S and Rajeev, AC and Raju, R}, title = {Decoding ATXN2 Phosphocode: Structural Insights and Therapeutic Opportunities in Disease.}, journal = {The protein journal}, volume = {}, number = {}, pages = {}, pmid = {40884740}, issn = {1875-8355}, abstract = {Ataxin-2 (ATXN2), a key RNA-binding protein, regulates RNA metabolism, stress granule formation, and neuronal homeostasis, with dysregulated phosphorylation contributing to Spinocerebellar Ataxia type 2 (SCA2), amyotrophic lateral sclerosis (ALS), and cancer. This review integrates structural biology, phosphoproteomics, and interactome analyses to map six critical phosphosites (S772, T741, S624, S684, S784, S889) within ATXN2's intrinsically disordered regions. Modulated by kinases GSK3β and CDK13 and phosphatases like INPP5F, these sites orchestrate interactions with RNA-binding partners (e.g., ATXN2L, FXR2, STAU2) and co-regulated proteins (e.g., TP53BP1, NUP153), driving pathogenesis through disrupted autophagy, nucleocytoplasmic transport, and stress granule dynamics. We propose targeted therapies, including GSK3β inhibitors for ALS, antisense oligonucleotides for SCA2, and MTOR modulators for cancer, to restore ATXN2 function. By elucidating phosphocode of ATXN2, this work highlights novel avenues for precision medicine in neurodegenerative and oncogenic diseases.}, } @article {pmid40884702, year = {2025}, author = {Hu, X and Wei, M and Zhang, H and Wang, M and Zhang, S and Li, B}, title = {Characteristics and influencing factors of pain in amyotrophic lateral sclerosis: a focus on symptom management.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {}, number = {}, pages = {}, pmid = {40884702}, issn = {1590-3478}, abstract = {PURPOSE: To investigate the characteristics and influencing factors of pain symptoms in ALS patients, provide references for the formulation of pain coping measures in clinical practice.

MATERIALS AND METHODS: The research design was a cross-sectional study.ALS patients were investigated using scales such as the Brief Pain Inventory (BPI). Binary logistic regression equation and multiple linear regression equation were used to analyze the influencing factors of whether occur pain and pain degree in ALS patients.

RESULTS: 149 (74.1%) patients had pain symptoms, and 51 (25.4%) patients had pain as the first symptom. Patients with moderate to severe pain accounted for 60.4%. Fatigue, social support, self-efficacy, and poor sleep quality have been associated with whether occur pain in ALS patients. Personality traits, education, fatigue, social support, physical function, and self-efficacy were associated with pain levels in ALS patients.

CONCLUSIONS: Pain is an important indicator of functional decline, which can directly affect the rehabilitation outcome, reduce the quality of life of patients, and is crucial for predicting disease progression and optimizing end-of-life care, which should arouse the full attention of clinical medical personnel and scientific researchers. In the future, it is necessary to strengthen pain intervention in rehabilitation programs.}, } @article {pmid40884436, year = {2025}, author = {Berry, JD and Bowser, R}, title = {Cardiac Troponin T in Tofersen-Treated SOD1 ALS Patients: Beginning to Resolve the Catch-22 of Identifying Treatment Responsive Biomarkers in ALS Drug Development.}, journal = {Muscle & nerve}, volume = {}, number = {}, pages = {}, doi = {10.1002/mus.70017}, pmid = {40884436}, issn = {1097-4598}, } @article {pmid40884086, year = {2025}, author = {Khamkar, AS and Jha, S and Bakhla, AK and Chauhan, G}, title = {Large-scale genetic study identifies shared genetic regions between cerebrovascular and neurodegenerative diseases.}, journal = {International journal of stroke : official journal of the International Stroke Society}, volume = {}, number = {}, pages = {17474930251377513}, doi = {10.1177/17474930251377513}, pmid = {40884086}, issn = {1747-4949}, abstract = {IntroductionCerebrovascular diseases (CeVD) and neurodegenerative diseases (ND) are two major neurological disorders, which are associated with increasing global morbidity and mortality. Population-based studies have indicated a complex link between CeVD and ND. However, the shared genetic etiology between these disease conditions remains less explored.MethodsWe conducted genome-wide genetic correlation analysis and investigated the shared genetic architecture through pleiotropy analysis between ND and CeVD, like stroke and its subtypes, to understand shared genetic factors and biological mechanisms. Publicly available large-scale genome-wide association studies (GWAS) summary statistics data of cross-ancestry, European and South Asian (SAS) ancestry were analyzed using methods implemented in the tools LDSC, PLACO, and COLOC.ResultsWe detected 116 shared genetic loci consisting of 770 lead pleiotropic SNPs (ND-CeVD P-range: 4.81×10-8 to 4.57×10-16) and 40 shared causal genetic regions (ND-CeVD PP.H4-range: 0.70-0.9, posterior probability of H4 (PP.H4) ≥ 0.7) between multiple CeVD and ND pairs. The genetic regions near ICA1L, HLA-DQA1, HLA-DRB1, MIR297, and PITX2 genes were identified as highly pleiotropic across multiple CeVD-ND pairs. We report ERGIC1 (5q35.1) for the first time as a shared causal genetic locus between Amyotrophic Lateral Sclerosis and small vessel stroke. The genetic risk score of stroke derived from the SAS population of the GIGASTROKE study was associated with ND (P-range=2.23×10-28 to 0.02), despite a small sample size compared to other ethnic groups, indicating high penetrance.ConclusionThe shared genetic loci and pathway analysis in this study provides new genes and pathways shared between ND and CeVD, which may help in a better understanding of disease mechanisms in these neurological diseases.}, } @article {pmid40883810, year = {2025}, author = {Downs, J}, title = {A shift or a substitution? On naming, exclusion, and co-production in longstanding eating disorders: matters arising from Lubieniecki et al. (2025).}, journal = {Journal of eating disorders}, volume = {13}, number = {1}, pages = {196}, pmid = {40883810}, issn = {2050-2974}, abstract = {This Matters Arising piece responds to the article by Lubieniecki et al. (2025), which explores lived experience perspectives on the 'SEED' (Severe and Enduring Eating Disorder) classification. Written from the standpoint of someone with lived experience of a longstanding eating disorder and professional involvement in research, policy, and service development, the piece supports Lubieniecki et al.'s analysis of 'SEED' as both validating and restrictive. It extends their work by situating the classification within a broader landscape of psychiatric labelling associated with treatment exclusion. The limitations of replacing 'SEED' with alternative terminology alone are considered, with emphasis on the need for corresponding reforms to care pathways and their provision. The author highlights how diagnostic language can serve not only descriptive but also administrative and prognostic functions, often reflecting institutional constraints rather than individual need. The importance of co-produced approaches to diagnostic frameworks is also discussed, with emphasis on embedding lived experience throughout classificationand service design.}, } @article {pmid40883656, year = {2025}, author = {García-Parra, B and Guiu, JM and Povedano, M and Modamio, P}, title = {Geographic distribution of amyotrophic lateral sclerosis-related genes: a systematic review.}, journal = {Neurodegenerative disease management}, volume = {}, number = {}, pages = {1-7}, doi = {10.1080/17582024.2025.2554382}, pmid = {40883656}, issn = {1758-2032}, abstract = {INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a rare motor neuron disease. There is no effective treatment, but disease-modifying therapies do exist. Objective. To identify the geographical distribution of ALS-related genes.

METHODS: A systematic review was conducted according to the PRISMA 2020 guidelines in PubMed and Web of Science. Inclusion criteria: patients with ALS, no age or gender restriction, English and Spanish languages, studies published until 31 July 2025.

RESULTS: Thirty-eight results were obtained, 32 were selected, 19 articles were assessed for eligibility, and 8 articles were included from databases. Three articles recommended by clinical experts were added, so 11 results were reviewed. This research showed that published articles on the geographic distribution of ALS-related genes are limited, particularly for underrepresented regions such as Africa.

CONCLUSION: The findings demonstrate the need for intensified international research to improve knowledge of the genetic epidemiology of ALS.}, } @article {pmid40881903, year = {2025}, author = {Shi, DD and Ding, J and Tian, J}, title = {Unraveling the enigma of salivary uric acid in periodontitis: Independent association, mechanistic insights, and future trajectories.}, journal = {World journal of clinical cases}, volume = {13}, number = {27}, pages = {108117}, doi = {10.12998/wjcc.v13.i27.108117}, pmid = {40881903}, issn = {2307-8960}, abstract = {This article explores the association between salivary uric acid (UA) and periodontitis, systematically analyzing its dual roles and research progress. Studies indicate that UA acts as a primary antioxidant in saliva under physiological conditions (accounting for 70%), protecting periodontal tissues by scavenging reactive oxygen species. However, when gum disease becomes severe, UA can switch roles and fuel inflammation, worsening tissue damage. Lorente et al's research found an independent inverse correlation between salivary UA levels and periodontitis severity (odds ratio = 6.14, P = 0.001), establishing 111 nmol/mL as a diagnostic threshold (area under the curve = 66%). Nevertheless, limitations include sample heterogeneity and failure to distinguish between gingivitis and periodontitis. Mechanistically, three hypotheses are proposed: The Antioxidant Depletion Hypothesis (UA oxidation consumption leading to feedback loops), the Microbial Metabolic Hijacking Hypothesis (pathogens utilizing UA as a carbon source to disrupt redox balance), and the Epithelial Barrier Dysfunction Hypothesis (UA deficiency causing downregulation of tight junction proteins). Future research should prioritize longitudinal cohorts to validate predictive value, integrate multi-omics to explore dysregulated signatures, and develop UA supplementation or targeted antioxidant therapies. This study provides novel insights into periodontitis diagnosis and mechanisms, advancing the application of salivary biomarkers in precision periodontics.}, } @article {pmid40881744, year = {2025}, author = {Zeppieri, M}, title = {Advantages and future outlooks in the use of telemedicine in liver transplantation.}, journal = {World journal of transplantation}, volume = {15}, number = {3}, pages = {104825}, doi = {10.5500/wjt.v15.i3.104825}, pmid = {40881744}, issn = {2220-3230}, abstract = {To maintain care during the coronavirus disease 2019 outbreak, telemedicine was implemented quickly. Jowell et al's pandemic study on telehealth integration and liver transplant evaluation is examined in this editorial. The study showed that telehealth did not affect clinical outcomes including time to evaluation, listing rates, or pre-transplant death. The study found that telehealth did not increase sociodemographic inequalities, suggesting a fair care framework. The editorial discusses how telemedicine in hepatology might help patients receive expert treatment while reducing logistical and financial burdens. Telehealth can democratize liver transplantation by delivering equivalent clinical results as in-person examinations. However, the editorial highlights technological barriers, difficulties in remotely assessing mental and physical health, and the need for specialized outreach to underserved communities. After the pandemic, telemedicine is essential to a more flexible, patient-centered healthcare system. The editorial encourages creativity and research to overcome challenges, improve hybrid care models, and ensure telehealth's egalitarian and successful potential. Pandemic insights can improve liver transplantation treatment and outcomes for diverse patient populations.}, } @article {pmid40881531, year = {2025}, author = {Chase, RC and Cortes, P and Lamb, CJ and Francis, D and DeVault, KR and Pang, M}, title = {Factors That Predict Endoscopic Evaluation and Gastrostomy Placement in Patients With Neurologic Disorders and Dysphagia.}, journal = {Cureus}, volume = {17}, number = {7}, pages = {e88853}, doi = {10.7759/cureus.88853}, pmid = {40881531}, issn = {2168-8184}, abstract = {BACKGROUND: Although patients with neurologic disorders commonly develop dysphagia, there remains little consensus on the role of initial esophagogastroduodenoscopy (EGD) or temporal guidance on gastrostomy placement. We aimed to characterize the predictors associated with EGD and gastrostomy recommendation at the initial gastroenterology consultation in patients with progressive neurologic disorders.

METHODS: This retrospective study spanned from December 31, 2010, to December 31, 2021, and included patients with both dysphagia and neurologic disorders. Multivariate logistic regression determined the predictors for EGD and gastrostomy recommendation after the initial visit.

RESULTS: Out of 273 patients, EGD was recommended for 163 (59.7%) at the initial evaluation. A diagnosis of amyotrophic lateral sclerosis (ALS) (odds ratio: 0.20; 95% confidence interval (CI): 0.07-0.52; P=0.001) and being referred by a neurologist (odds ratio: 0.37; 95% CI: 0.17-0.84; P<0.02) were the negative predictors of an initial EGD recommendation. Gastrostomy was recommended for 38 patients (13.9%) at the initial consultation. Dysphagia to both liquids and solids, body mass index, diagnosis of ALS, and clinical frailty scale scores were associated with gastrostomy (P≤0.01). A model of six variables had high predictive accuracy for EGD recommendation (area under the receiver operating characteristic curve: 0.7741).

CONCLUSIONS: This study proposes a predictive model for initial EGD recommendation. We suggest that when considered in conjunction with the predictive clinical features of ALS diagnosis and dysphagia to both solids and liquids, the clinical frailty scale and American Society of Anesthesiologists physical status classification system scores may help clinicians anticipate gastrostomy when applied to patients with any neurologic disorder.}, } @article {pmid40881516, year = {2025}, author = {Swarnakar, R}, title = {Brain-Computer Interfaces in Rehabilitation: Implementation Models and Future Perspectives.}, journal = {Cureus}, volume = {17}, number = {7}, pages = {e88873}, doi = {10.7759/cureus.88873}, pmid = {40881516}, issn = {2168-8184}, abstract = {Brain-computer interfaces (BCIs) represent an emerging advancement in rehabilitation, enabling direct communication between the brain and external devices to aid recovery in individuals with neurological impairments. BCIs can be classified into invasive, semi-invasive, non-invasive, or hybrid types. By interpreting neural signals and converting them into control commands, BCIs can bypass damaged pathways, offering therapeutic potential for conditions such as stroke, spinal cord injury, traumatic brain injury, and neurodegenerative diseases such as amyotrophic lateral sclerosis. BCIs' current applications, such as motor restoration via robotic exoskeletons and functional electrical stimulation, cognitive enhancement through neurofeedback and attention training, and communication tools for individuals with severe physical limitations, are largely being explored within research settings and are not yet part of routine clinical practice. Advances in EEG signal acquisition, machine learning, wearable and wireless systems, and integration with virtual reality are enhancing the clinical utility of BCIs by improving accuracy, adaptability, and usability. However, widespread clinical adoption faces challenges, including signal variability, training complexity, data privacy, and ethical and regulatory issues. Ethical challenges in BCI include issues related to the ownership and misuse of brain data, risks of neural interference, threats to autonomy and personal identity, as well as concerns around data privacy, user consent, emotional manipulation, and accountability in neural interventions. In this context, this editorial has also proposed one model (NEURO model checklist) for BCI implementation in rehabilitation. The future of BCIs in rehabilitation lies in developing personalized, closed-loop, and home-based systems, enabled by interdisciplinary collaboration among clinicians, engineers, neuroscientists, and policymakers. With continued research and ethical implementation, BCIs have the potential to transform neurorehabilitation and greatly enhance patient outcomes and quality of life.}, } @article {pmid40879853, year = {2025}, author = {Tu, JY}, title = {Letter to the Editor- The association between sarcopenic obesity and depression in middle-aged and elderly U.S. adults: insights from the NHANES study.}, journal = {Aging clinical and experimental research}, volume = {37}, number = {1}, pages = {260}, pmid = {40879853}, issn = {1720-8319}, mesh = {Humans ; *Sarcopenia/complications/psychology/epidemiology ; *Obesity/complications/epidemiology/psychology ; Aged ; *Depression/epidemiology/complications ; Middle Aged ; Nutrition Surveys ; United States/epidemiology ; Male ; Female ; }, abstract = {After reading "The association between sarcopenic obesity and depression in middle-aged and elderly U.S. adults: insights from the NHANES study", we sincerely appreciate Zhang et al.'s exploration of the relationship between sarcopenic obesity and depression in middle-aged and elderly populations, which provides new clinical perspectives for preventing sarcopenic obesity and depression. However, to more rigorously and clearly elucidate this relationship, several concerns must be addressed.}, } @article {pmid40879603, year = {2025}, author = {Karimi, S and Ghaheri, A and Madani, H and Beheshti Maal, A and Sadri, B and Khodadoust, E and Sharafi, F and Vosough, M and Nabavi, SM}, title = {Intravenous vs intrathecal transplantation of allogeneic GMP/GCP compliant Wharton's jelly mesenchymal stromal cells in ALS patients: a phase I study.}, journal = {Neurodegenerative disease management}, volume = {}, number = {}, pages = {1-9}, doi = {10.1080/17582024.2025.2553499}, pmid = {40879603}, issn = {1758-2032}, abstract = {INTRODUCTION: There are a few therapeutic approaches for Amyotrophic Lateral Sclerosis (ALS) which can only slow down or stop the disease progression for a limited period of time. Since it has been proven that Mesenchymal Stromal Cells (MSCs) produce neurotrophic factors and have some neuroprotective effects, stem cell therapy has been proposed as an alternative or add-on treatment for ALS patients.

METHOD & MATERIAL: In this open-label clinical trial, two-repeated dose of 60 million GMP compliant Wharton's Jelly-derived Mesenchymal Stromal Cells (WJ-MSCs) were transplanted intrathecally (#6 patients) or intravenously (#6 patients) twice with a 3-month interval.

RESULTS: No adverse events related to the intervention or injected cells were reported. While no significant improvement in the total revised amyotrophic lateral sclerosis functional rating scale (ALSFRS-R) score or overall clinical efficacy was achieved, patients reported improvements in specific sub-items such as salivation, swallowing, and their speech. Additionally, reductions in muscle tremors and fasciculations, as well as increased muscle strength were observed.

CONCLUSION: In conclusion, using WJ-MSCs is safe and feasible in ALS patients, but the efficacy of these cells should be assessed in future studies with more patients, different routes of cell administration, and maybe with higher doses of the injected cells.}, } @article {pmid40879079, year = {2025}, author = {Talbot, K and Thompson, AG}, title = {Unpacking the relationship between exercise and amyotrophic lateral sclerosis.}, journal = {Brain : a journal of neurology}, volume = {}, number = {}, pages = {}, doi = {10.1093/brain/awaf310}, pmid = {40879079}, issn = {1460-2156}, } @article {pmid40878928, year = {2025}, author = {Chakraborty, A and Benassy, MN and Weil, D and Kundu, B}, title = {Optineurin Localization at the Centrosome, Spindle, and Midbody Implies Its Role in Cell Division.}, journal = {Cytoskeleton (Hoboken, N.J.)}, volume = {}, number = {}, pages = {}, doi = {10.1002/cm.70015}, pmid = {40878928}, issn = {1949-3592}, abstract = {Optineurin (OPTN), a multifunctional cytosolic protein, is recognized as an autophagy adaptor. Its association with neurodegenerative diseases, like ALS, triggered extensive research. OPTN has been found in intracellular organelles, including the mitochondria, Golgi body, endosomes, microtubules, and the nucleus. The report of mitotic defects and delayed cell division in OPTN-depleted cells prompted us to explore OPTN's exact localization in the cell that could interfere with cell division assemblies. We used three distinct human cell lines, HeLa, HEK293, and SH-SY5Y, and probed them for OPTN localization using both centrosomal (Aurora A kinase, pericentrin, PCM1, Cep170, and γ-tubulin) and mitotic spindle markers (β-tubulin). Our immunofluorescence-based detection using wide-field fluorescence, confocal, and structured illumination microscopy (SIM) placed OPTN at the centrosome, which remained associated with the centriole after duplication and their migration during mitosis. OPTN was also observed at the junction of daughter cells during cytokinesis. Our finding reveals unmapped localizations of OPTN with key cytosolic assemblies that are directly involved in cell division.}, } @article {pmid40878817, year = {2025}, author = {Lester, DG and Talbot, K and Turner, MR and Thompson, AG and , }, title = {A Validated Model to Predict Severe Weight Loss in Amyotrophic Lateral Sclerosis.}, journal = {Annals of clinical and translational neurology}, volume = {}, number = {}, pages = {}, doi = {10.1002/acn3.70129}, pmid = {40878817}, issn = {2328-9503}, support = {Lester/2450/795/MNDA_/Motor Neurone Disease Association/United Kingdom ; Thompson/Jan20/952-795/MNDA_/Motor Neurone Disease Association/United Kingdom ; MR/T006927/1/MRC_/Medical Research Council/United Kingdom ; MR/Y001095/1/MRC_/Medical Research Council/United Kingdom ; }, abstract = {Severe weight loss in amyotrophic lateral sclerosis (ALS) is common, multifactorial, and associated with shortened survival. Using longitudinal weight data from over 6000 patients with ALS across three cohorts, we built an accelerated failure time model to predict the risk of future severe (≥ 10%) weight loss using five single-timepoint clinical predictors: symptom duration, revised ALS Functional Rating Scale, site of onset, forced vital capacity, and age. Model performance and generalisability were evaluated using internal-external cross-validation and random-effects meta-analysis. The overall concordance statistic was 0.71 (95% CI 0.63-0.79), and the calibration slope and intercept were 0.91 (0.69-1.13) and 0.05 (-0.11-0.21). This study highlights clinical factors most associated with severe weight loss in ALS and provides the basis for a stratification tool.}, } @article {pmid40878665, year = {2025}, author = {Abrahao, A and Da Silva, P and Ciepielewska, M and Zinman, L}, title = {Real-world safety and tolerability of intravenous edaravone in patients with amyotrophic lateral sclerosis.}, journal = {Neurodegenerative disease management}, volume = {}, number = {}, pages = {1-8}, doi = {10.1080/17582024.2025.2552610}, pmid = {40878665}, issn = {1758-2032}, abstract = {AIMS: This retrospective cohort study describes real-world safety and tolerability outcomes in United States-based edaravone-treated patients with ALS.

PATIENTS & METHODS: Amerita Specialty Infusion Services provided IV edaravone to patients with ALS treated with their first dose between 25 September 2017-30 September 2022. Mean ALS Functional Rating Scale-Revised (ALSFRS-R) scores and forced vital capacity (FVC) %-predicted measures were recorded within ± 100 days from care initiation to approximate baseline values.

RESULTS: Included patients (n = 243) received/were still receiving IV edaravone/edaravone oral suspension as of 30 September 2022. At initiation, 66.7% were male, mean age ± SD was 61.2 ± 11.2 years, and 61.3% were covered by government insurance. In patients with provider-recorded ALSFRS-R (n = 115) and FVC (n = 84) %-predicted measures within ± 100 days from care initiation, mean ± SD values were 35.1 ± 8.9 and 72.3% ± 21.7%, respectively. Mean ± SD therapy duration was 13.5 ± 11.4 months. Discontinuation reasons included death/hospice (n = 82), patient's choice (n = 38), doctor's choice (n = 31), insurance (n = 18), and other (n = 12). Reasons for IV edaravone discontinuation and IV edaravone administration access device were not associated.

CONCLUSIONS: Treatment discontinuation was primarily related to ALS disease progression/death, rather than safety or tolerability. This study representative of real-world patients with ALS suggests that edaravone showed consistent safety and tolerability profiles with previous studies.}, } @article {pmid40878249, year = {2025}, author = {Silva, MM and Cunha, EM and Briois, V and Rochet, A}, title = {Unraveling hydride dynamics on cubic palladium nanoparticles.}, journal = {Physical chemistry chemical physics : PCCP}, volume = {}, number = {}, pages = {}, doi = {10.1039/d5cp02672e}, pmid = {40878249}, issn = {1463-9084}, abstract = {Palladium-based materials exhibit a high affinity for hydrogen molecules, enabling the effortless formation of a hydride phase. This property is widely exploited in several catalytic reactions and hydrogen storage materials. However, the effects of morphological parameters, support interactions, and formation kinetics remain incompletely understood. In this work, we applied in situ time-resolved X-ray absorption spectroscopy (XAS) to investigate the impact of nanoparticle sizes and support materials on the dynamic formation of palladium hydrides during thermal treatment under H2. A detailed analysis using multivariate curve resolution with alternating least squares (MCR-ALS) enabled the extraction of concentration profiles and the identification of pure species involved in the process, thereby revealing distinct kinetic behaviours across the samples. This study provides valuable insights into how particle size and support influence the kinetics of hydrogen absorption in palladium systems, which can significantly impact catalytic performance.}, } @article {pmid40877115, year = {2025}, author = {Hu, N and Ding, J and Tian, H and Shen, D and Yang, X and Niu, J and Liu, M and Cui, L}, title = {Impacts of oral supplementation of vitamin B12 and plasma levels of homocysteine on progression and survival in a Chinese ALS cohort.}, journal = {Neurological research}, volume = {}, number = {}, pages = {1-9}, doi = {10.1080/01616412.2025.2553147}, pmid = {40877115}, issn = {1743-1328}, abstract = {OBJECTIVE: We investigate the impact of plasma levels of folate, vitamin B12 (VB12), homocysteine (HCY) and oral supplementation of folate and VB12 on amyotrophic lateral sclerosis (ALS) progression and survival.

METHODS: Patients with sporadic ALS were consecutively enrolled and regularly followed up. Oral supplementation of folate and VB12 was recommended to all involved patients. Tests of plasma levels of folate, VB12 and HCY were conducted before or after medication.

RESULTS: A total of 120 sporadic ALS patients with results of plasma folate, VB12 or HCY were finally included. Oral supplementation of VB12 significantly increased the plasma levels of folate (p < 0.01) and VB12 (p < 0.01), and lower HCY (p < 0.001). The progression rate of ALS patients in the first 3-6 months was negatively related to the plasma level of VB12 (p = 0.008). After taking VB supplements, the progression rate in the first 3-6 months was comparable to previous progression rate (p = 0.102) and significantly lower than that in the 9-12 month follow-up (p < 0.01). There was no significant difference in survival time between the two groups that took VB12 and those who did not take it neither between patients with high and low serum levels of folate, VB12 or HCY.

CONCLUSION: Oral intake of VB12 supplements may significantly increase plasma levels of folate and VB12 and decrease plasma levels of HCY in ALS patients. Oral supplementation of folate and VB12, and subsequent high levels of VB12 in serum, may lower the ALS progression at the early stages but show no significant impact on ALS survival time.}, } @article {pmid40876628, year = {2025}, author = {Pytel, D and Longo, JF}, title = {The Proteostasis Network in Proteinopathies: Mechanisms and Interconnections.}, journal = {The American journal of pathology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ajpath.2025.07.011}, pmid = {40876628}, issn = {1525-2191}, abstract = {Proteinopathies are neurodegenerative disorders that are characterized by accumulation of misfolded toxic protein aggregates that lead to synaptic and neuronal dysfunction. Though genetically, clinically and pathologically distinct, a common feature of these diseases is disruption of protein homeostasis (proteostasis), which causes accumulation of misfolded proteins. The machinery mediating proteostasis exquisitely balances and interlaces protein synthesis, protein folding and trafficking, and protein degradation processes within the proteostasis network to maintain homeostasis. The proteostasis network governs a functional and dynamic proteome by modulating the timing, location, and stoichiometry of protein expression, surveillance and maintenance of protein folding and removal of misfolded or excess proteins. Although a functional proteome is essential for the health of all cell types, this is especially true for neurons which are prone to enhanced cellular stress. Aging is the most important risk factor for proteostasis decline and the development of proteinopathies. However, germline and somatic mutations can also functionally impair components of the proteostasis network. Post-mitotic cells, particularly neurons, are rendered further susceptible to proteostasis dysfunction due to their extended lifespan. This review discusses the interconnections between the functional components mediating proteostasis in neuronal cells and how aberrations in proteostasis contribute to neuronal dysfunction and disease.}, } @article {pmid40876427, year = {2025}, author = {Ibrahim, SI and Zaher, DM and Hersi, FA and Hamouda, AO and Al Hindawi, MA and Omar, HA}, title = {Repurposing edaravone in oncology: Bridging antioxidant defense and immune modulation.}, journal = {International immunopharmacology}, volume = {164}, number = {}, pages = {115413}, doi = {10.1016/j.intimp.2025.115413}, pmid = {40876427}, issn = {1878-1705}, abstract = {Edaravone, a synthetic free radical scavenger originally approved for neurological disorders such as stroke and amyotrophic lateral sclerosis (ALS), is gaining attention for its emerging potential role in cancer. Beyond its well-established antioxidant properties, edaravone demonstrates significant anti-inflammatory and immunomodulatory activities, including the inhibition of key pathways such as NF-κB, JAK2/STAT3, and TLR4/IL-6, suggesting potential to modulate immune responses within the tumor microenvironment. This review discusses how edaravone disrupts oncogenic signaling, induces cell cycle arrest, and enhances apoptosis, particularly in cancer stem cells and therapy-resistant models. It also examines edaravone's dual role in combination therapies, where it may improve the cytotoxicity of chemotherapeutic and radiotherapeutic agents while simultaneously protecting normal tissues from treatment-induced toxicities. By linking mechanistic insights with therapeutic outcomes, this review highlights the rationale for repurposing edaravone as a potential adjuvant in cancer therapy. Although clinical data are currently limited, preliminary findings are encouraging and warrant further investigation into edaravone's potential use in cancer treatment regimens.}, } @article {pmid40875997, year = {2025}, author = {Kaufman Goldberg, T and Hadlock, TA}, title = {Invited Commentary on: Frants et al.'s "Dual Innervation of the Depressor Labii Inferioris and Implications for Deep Plane Facelift and Structural Neck Contouring": Converging Evidence for Cervical Branch Innervation of the Depressor Labii Inferioris.}, journal = {Facial plastic surgery & aesthetic medicine}, volume = {27}, number = {5}, pages = {406-407}, doi = {10.1177/26893614251370279}, pmid = {40875997}, issn = {2689-3622}, } @article {pmid40875690, year = {2025}, author = {Abdallah, W and Picard-Turcot, MA and Lafontaine-Trudel, I and Codsi, E and Wavrant, S and Carmant, L and Raboisson, MJ and Khalil, A and Audibert, F}, title = {Prediction of dual twin survival after laser for twin-to-twin transfusion syndrome.}, journal = {Fetal diagnosis and therapy}, volume = {}, number = {}, pages = {1-14}, doi = {10.1159/000547995}, pmid = {40875690}, issn = {1421-9964}, abstract = {OBJECTIVES: To evaluate the predictive value of sonographic parameters at diagnosis of Twin-to-Twin Transfusion Syndrome (TTTS) treated with fetoscopic laser photocoagulation for post-natal dual twin survival, and to validate Krispin et al's calculator.

METHODS: This is a retrospective cohort study of cases of TTTS treated by FLPC. The primary outcome was dual survival 30 days after delivery. The calculator used preoperative variables: donor's estimated fetal weight (EFW)<10th centile, intertwin growth discordance >25%, anterior placenta, pulsatility index (PI) in the umbilical artery (UA), ductus venosus (DV) and middle cerebral artery (MCA), with scores ranging 0-300.

RESULTS: Among 157 patients, 84 (53.5%) had dual twin survival (A), compared to 73 (46.5%) with one or no survivors (B). No significant differences were seen in donor's EFW <10th centile (57.1%(A) vs. 57.5%(B), p=0.96), intertwin growth discordance (26.2%(A) vs. 38.4%(B) p=0.95), rates of PI>95th centile in the donor's UA and DV, and PI<5th centile in the MCA (p>0.05). However, a significant difference was found for anterior placenta (38.1% (A) vs. 58.9% (B), p=0.009). The observed dual survival was higher than predicted for scores ≥100.

CONCLUSIONS: We did not externally validate the calculator of dual survival after laser for TTTS, especially for elevated scores.}, } @article {pmid40875372, year = {2025}, author = {Ghaffari, LT and Welebob, EA and Newton, SEB and Boehringer, AV and Cyliax, KL and Pasinelli, P and Trotti, D and Haeusler, AR}, title = {Neuronal Activity-Dependent Gene Dysregulation in C9orf72 i[3]Neuronal Models of ALS/FTD Pathogenesis.}, journal = {American journal of physiology. Cell physiology}, volume = {}, number = {}, pages = {}, doi = {10.1152/ajpcell.00238.2025}, pmid = {40875372}, issn = {1522-1563}, support = {RF1NS114128//HHS | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; R01NS114128//HHS | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; R01NS109150//HHS | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; NA//Farber Family Foundation/ ; NA//Aldrich Foundation/ ; }, abstract = {The GGGGCC nucleotide repeat expansion (NRE) mutation in the C9orf72 (C9) gene is the most common cause of ALS and FTD. Neuronal activity plays an essential role in shaping biological processes within both healthy and neurodegenerative disease scenarios. Here, we show that at baseline conditions, C9-NRE iPSC-cortical neurons display aberrations in several pathways, including synaptic signaling and transcriptional machinery, potentially priming diseased neurons for an altered response to neuronal stimulation. Indeed, exposure to two pathophysiologically relevant stimulation modes, prolonged membrane depolarization, or a blockade of K[+] channels, followed by RNA sequencing, induces a temporally divergent activity-dependent transcriptome of C9-NRE cortical neurons compared to healthy controls. This study provides new insights into how neuronal activity influences the ALS/FTD-associated transcriptome, offering a dataset that enables further exploration of pathways necessary for conferring neuronal resilience or degeneration.}, } @article {pmid40875341, year = {2025}, author = {Dang, J and Xiao, S}, title = {A meta-analytic reassessment of the vicious cycle of psychopathology and stressful life events: Commentary on Rnic et al. (2023).}, journal = {Psychological bulletin}, volume = {151}, number = {7}, pages = {930-939}, doi = {10.1037/bul0000475}, pmid = {40875341}, issn = {1939-1455}, mesh = {Humans ; *Stress, Psychological/psychology ; *Life Change Events ; *Mental Disorders/psychology/epidemiology ; Psychopathology ; }, abstract = {Rnic et al. (2023) conducted a comprehensive multilevel meta-analysis examining the stress generation hypothesis across various forms of psychopathology. They utilized the bivariate correlation between psychopathology at Time 1 and stress at Time 2 to estimate effect sizes. To address potential confounding from baseline stress assessments, we reanalyzed the data by (a) using the cross-lagged association in a multilevel meta-analysis to examine longitudinal links between Time 1 psychopathology and Time 2 stress and (b) incorporating Time 1 stress as a control variable in a meta-analytic structural equation model. Based on a subset of Rnic et al.'s original data set (33 studies with 18,684 participants and 126 effect sizes), our findings revealed cross-lagged associations of rC.L = .12 for the predictive effect of baseline psychopathology, especially internalizing psychopathology, on subsequent dependent stress and rC.L = .06 for independent stress. These effects were homogeneous across diverse samples, measures, and contexts. Moreover, even after controlling for Time 1 stress, dependent stress continued to mediate the relationship between baseline psychopathology and subsequent symptoms, whereas independent stress did not mediate, underscoring the role of dependent stress in perpetuating the cycle of stress and psychopathology. (PsycInfo Database Record (c) 2025 APA, all rights reserved).}, } @article {pmid40875336, year = {2025}, author = {Yuan, Z and Yin, J and Sun, J}, title = {The paradox of team conflict revisited: An updated meta-analysis of the team conflict-team performance relationships.}, journal = {The Journal of applied psychology}, volume = {}, number = {}, pages = {}, doi = {10.1037/apl0001315}, pmid = {40875336}, issn = {1939-1854}, abstract = {The possibility that team conflict, especially task conflict, might improve team performance has stimulated a large body of empirical research that continues to grow to this day. Nevertheless, 12 years has passed since de Wit et al.'s (2012) comprehensive meta-analysis. To synthesize the even larger body of empirical evidence now available, we provide an updated meta-analysis of the team conflict-team performance relationships by revisiting the population average estimates and their effect size heterogeneity. Given the recent developments in the team conflict literature, we also incorporate status conflict into our synthesis. Moreover, to shed light on the contextual factors that may help explain the heterogeneous team conflict-team performance relationships, we examine a host of moderators pertaining to national culture, team features, and research methods. Our results based on psychometric meta-analysis indicate that all four team conflict dimensions (i.e., task conflict, relationship conflict, process conflict, and status conflict) are negatively related to team performance. Moreover, the relationships of task conflict and relationship conflict with team performance have substantial cross-situation heterogeneity. Examining the contingencies of these heterogeneous relationships, our metaregression analyses reveal that national culture (e.g., individualism), team features (e.g., team performance facet), and methodological factors (e.g., team conflict scale) all play important roles in helping to explain the mixed effects of team conflict on team performance. Based on our quantitative synthesis, we discuss the implications for the next waves of team conflict research. (PsycInfo Database Record (c) 2025 APA, all rights reserved).}, } @article {pmid40874900, year = {2025}, author = {Shive, M and Hawryluk, E and Drucker, AM and Frazer-Green, L}, title = {Response to Chu et al's "Atopic dermatitis (eczema) guidelines: 2023 American Academy of Allergy, Asthma and Immunology/American College of Allergy, Asthma and Immunology Joint Task Force on Practice Parameters GRADE- and Institute of Medicine-based recommendations".}, journal = {Journal of the American Academy of Dermatology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jaad.2025.07.061}, pmid = {40874900}, issn = {1097-6787}, } @article {pmid40873038, year = {2025}, author = {Dulski, J and Boddapati, AK and Risi, B and Iruzubieta, P and Orlacchio, A and Fernández-Torrón, R and Castillo-Triviño, T and López de Munain, A and Vucic, S and Padovani, A and Kaat, LD and Barakat, TS and Petrucelli, L and Prudencio, M and Landers, JE and Weishaupt, JH and Prokop, A and Filosto, M and Wszolek, ZK and Pant, DC}, title = {Targeted plasma proteomics uncover proteins associated with KIF5A-linked SPG10 and ALS spectrum disorders.}, journal = {HGG advances}, volume = {}, number = {}, pages = {100498}, doi = {10.1016/j.xhgg.2025.100498}, pmid = {40873038}, issn = {2666-2477}, abstract = {KIF5A (Kinesin family member 5A) is a motor protein that functions as a key component of the axonal transport machinery. Variants in KIF5A are linked to several neurodegenerative diseases, mainly spastic paraplegia type 10 (SPG10), Charcot-Marie-Tooth disease type 2 (CMT2), and amyotrophic lateral sclerosis (ALS). These diseases share motor neuron involvement but vary significantly in clinical presentation, severity, and progression. KIF5A variants are mainly categorized into N-terminal variants associated with SPG10/CMT2 and C-terminal variants linked to ALS. This study utilized a multiplex NULISA targeted platform to analyze plasma proteome from KIF5A-linked SPG10, ALS individuals and compared to healthy controls. Our results revealed distinct proteomic signatures, with significant alterations in proteins related to synaptic function, and inflammation. Notably, neurofilament light polypeptide, a biomarker for neurodegenerative diseases, was elevated in KIF5A ALS but not in SPG10 individuals. Moreover, these findings can now be taken forward to gain mechanistic understanding of axonopathies linking to N- versus C-terminal KIF5A variants affecting both central and peripheral nervous systems.}, } @article {pmid40872233, year = {2025}, author = {Garcia-Sherman, MC and Hamid, SA and Jackson, DN and Thomas, J and Lipke, PN}, title = {Functional Amyloids in Adhesion of Non-albicans Candida Species.}, journal = {Pathogens (Basel, Switzerland)}, volume = {14}, number = {8}, pages = {}, doi = {10.3390/pathogens14080723}, pmid = {40872233}, issn = {2076-0817}, support = {1R01GM098616-01/NH/NIH HHS/United States ; }, mesh = {Humans ; *Cell Adhesion ; *Candida/physiology/metabolism ; *Amyloid/metabolism ; Biofilms/growth & development ; Fungal Proteins/metabolism ; Candida albicans ; Candidiasis/microbiology ; Epithelial Cells/microbiology ; }, abstract = {Candida fungal species are the most common fungal opportunistic pathogens. Their ability to form antifungal resistant biofilms contributes to their increasing clinical frequency. These fungi express surface-anchored adhesins including members of the Als family. These adhesins mediate epithelial adhesion, aggregation, and biofilm formation. Many of the adhesins contain cross-β core sequences that form amyloid-like protein aggregates on the fungal surface. The aggregates mediate high-avidity bonding that contributes to biofilm establishment and persistence. Accordingly, autopsy sections from individuals with candidiasis and other mycoses have amyloids within abscesses. An amyloid-forming peptide containing a sequence from Candida albicans Als5 bound to C. albicans, C. tropicalis, and C. parapsilosis. C. albicans and C. tropicalis aggregated with beads coated with serum albumin, and the aggregates stained with the amyloid-binding dye thioflavin T. Additionally, an Als5-derived amyloid-inhibiting peptide blocked cell aggregation. The amyloid-inhibiting peptide also blocked C. albicans, C. tropicalis, and C. parapsilosis adhesion to monolayers of FaDu epithelial cells. These results show the involvement of amyloid-like interactions in pathogenesis in several Candida species.}, } @article {pmid40871062, year = {2025}, author = {Yang, HM}, title = {Overcoming the Blood-Brain Barrier: Advanced Strategies in Targeted Drug Delivery for Neurodegenerative Diseases.}, journal = {Pharmaceutics}, volume = {17}, number = {8}, pages = {}, doi = {10.3390/pharmaceutics17081041}, pmid = {40871062}, issn = {1999-4923}, support = {03-2025-0200//Seoul National University Hospital/ ; }, abstract = {The increasing global health crisis of neurodegenerative diseases such as Alzheimer's, Parkinson's, amyotrophic lateral sclerosis, and Huntington's disease is worsening because of a rapidly increasing aging population. Disease-modifying therapies continue to face development challenges due to the blood-brain barrier (BBB), which prevents more than 98% of small molecules and all biologics from entering the central nervous system. The therapeutic landscape for neurodegenerative diseases has recently undergone transformation through advances in targeted drug delivery that include ligand-decorated nanoparticles, bispecific antibody shuttles, focused ultrasound-mediated BBB modulation, intranasal exosomes, and mRNA lipid nanoparticles. This review provides an analysis of the molecular pathways that cause major neurodegenerative diseases, discusses the physiological and physicochemical barriers to drug delivery to the brain, and reviews the most recent drug targeting strategies including receptor-mediated transcytosis, cell-based "Trojan horse" approaches, gene-editing vectors, and spatiotemporally controlled physical methods. The review also critically evaluates the limitations such as immunogenicity, scalability, and clinical translation challenges, proposing potential solutions to enhance therapeutic efficacy. The recent clinical trials are assessed in detail, and current and future trends are discussed, including artificial intelligence (AI)-based carrier engineering, combination therapy, and precision neuro-nanomedicine. The successful translation of these innovations into effective treatments for patients with neurodegenerative diseases will require essential interdisciplinary collaboration between neuroscientists, pharmaceutics experts, clinicians, and regulators.}, } @article {pmid40870776, year = {2025}, author = {Semyalo, D and Joshi, R and Kim, Y and Omia, E and Alal, LB and Kim, MS and Baek, I and Cho, BK}, title = {Short-Wavelength Infrared Hyperspectral Imaging and Spectral Unmixing Techniques for Detection and Distribution of Pesticide Residues on Edible Perilla Leaves.}, journal = {Foods (Basel, Switzerland)}, volume = {14}, number = {16}, pages = {}, doi = {10.3390/foods14162864}, pmid = {40870776}, issn = {2304-8158}, support = {N/A//Chungnam National University/ ; }, abstract = {Pesticide residue analysis of agricultural produce is vital because of associated health concerns, highlighting the need for effective non-destructive techniques. This study introduces a method that combines short-wavelength infrared hyperspectral imaging with spectral unmixing to detect chlorfenapyr and azoxystrobin residues on perilla leaves. Sixty-six leaves were treated with pesticides at concentrations between 0 and 0.06%. The study utilized multicurve resolution-alternating least squares (MCR-ALS), a spectral unmixing method, to identify and visualize the distribution of pesticide residues. This technique achieved lack-of-fit values of 1.03% and 1.78%, with an explained variance of 99% for both pesticides. Furthermore, a quantitative model was developed that integrates insights from MCR-ALS with Gaussian process regression to estimate chlorfenapyr residue concentrations, resulting in a root mean square error of double cross-validation (RMSEV) of 0.0012% and a double cross-validation coefficient of determination (R[2]v) of 0.99. Compared to other chemometric approaches, such as partial least squares regression and support vector regression, the proposed integrated method decreased RMSEV by 67.57% and improved R[2]v by 2.06%. The combination of hyperspectral imaging with spectral unmixing offers advancements in the real-time monitoring of agricultural product safety, supporting the delivery of high-quality fresh vegetables to consumers.}, } @article {pmid40870005, year = {2025}, author = {Jeong, J and Kim, J and Kim, MS}, title = {Dual Nature of Mitochondrial Integrated Stress Response: Molecular Switches from Protection to Pathology.}, journal = {Genes}, volume = {16}, number = {8}, pages = {}, doi = {10.3390/genes16080957}, pmid = {40870005}, issn = {2073-4425}, mesh = {Humans ; *Mitochondria/metabolism/pathology/genetics ; *Stress, Physiological ; Animals ; *Amyotrophic Lateral Sclerosis/metabolism/drug therapy/pathology/genetics ; }, abstract = {BACKGROUND: The mitochondrial integrated stress response (ISR) represents a fundamental cellular adaptation mechanism with dual protective and pathological roles. We critically analyzed current literature on ISR mechanisms, focusing on recent paradigm shifts including the 2020 discovery of the OMA1-DELE1-HRI axis, emerging controversies over context-dependent activation patterns, and the January 2025 clinical trial failures that have reshaped the therapeutic landscape.

METHODS: We reviewed recent literature (2020-2025) examining ISR mechanisms, clinical trials, and therapeutic developments through comprehensive database searches.

RESULTS: The field has evolved from simple linear pathway models to recognition of complex, context-dependent networks. Recent findings reveal that ISR activation mechanisms vary dramatically based on cellular metabolic state, with distinct pathways operating in proliferating versus differentiated cells. The "dark microglia" phenotype in neurodegeneration and DR5-mediated apoptotic switches exemplify pathological ISR manifestations, while adaptive responses include metabolic reprogramming and quality control enhancement.

CONCLUSIONS: The 2025 failures of DNL343 and ABBV-CLS-7262 in ALS trials underscore the need for precision medicine approaches that account for context-dependent ISR functions, temporal dynamics, and disease-specific mechanisms.}, } @article {pmid40869392, year = {2025}, author = {Șerban, M and Toader, C and Covache-Busuioc, RA}, title = {Blueprint of Collapse: Precision Biomarkers, Molecular Cascades, and the Engineered Decline of Fast-Progressing ALS.}, journal = {International journal of molecular sciences}, volume = {26}, number = {16}, pages = {}, doi = {10.3390/ijms26168072}, pmid = {40869392}, issn = {1422-0067}, mesh = {*Amyotrophic Lateral Sclerosis/metabolism/genetics/pathology/diagnosis ; Humans ; *Biomarkers/metabolism ; Disease Progression ; Animals ; Mitochondria/metabolism ; Precision Medicine ; Neurofilament Proteins/metabolism ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is still a heterogeneous neurodegenerative disorder that can be identified clinically and biologically, without a strong set of biomarkers that can adequately measure its fast rate of progression and molecular heterogeneity. In this review, we intend to consolidate the most relevant and timely advances in ALS biomarker discovery, in order to begin to bring molecular, imaging, genetic, and digital areas together for potential integration into a precision medicine approach to ALS. Our goal is to begin to display how several biomarkers in development (e.g., neurofilament light chain (NfL), phosphorylated neurofilament heavy chain (pNfH), TDP-43 aggregates, mitochondrial stress markers, inflammatory markers, etc.) are changing our understanding of ALS and ALS dynamics. We will attempt to provide a framework for thinking about biomarkers in a systematic way where our candidates are not signals alone but part of a tethered pathophysiological cascade. We are particularly interested in the fast progressor phenotype, a devastating and under-characterized subset of ALS due to a rapid axonal degeneration, early respiratory failure, and very short life span. We will try to highlight the salient molecular features of this ALS subtype, including SOD1 A5V toxicity, C9orf72 repeats, FUS variants, mitochondrial collapse, and impaired autophagy mechanisms, and relate these features to measurable blood and CSF (biomarkers) and imaging platforms. We will elaborate on several interesting tools, for example, single-cell transcriptomics, CSF exosomal cargo analysis, MRI techniques, and wearable sensor outputs that are developing into high-resolution windows of disease progression and onset. Instead of providing a static catalog, we plan on providing a conceptual roadmap to integrate biomarker panels that will allow for earlier diagnosis, real-time disease monitoring, and adaptive therapeutic trial design. We hope this synthesis will make a meaningful contribution to the shift from observational neurology to proactive biologically informed clinical care in ALS. Although there are still considerable obstacles to overcome, the intersection of a precise molecular or genetic association approach, digital phenotyping, and systems-level understandings may ultimately redefine how we monitor, care for, and treat this challenging neurodegenerative disease.}, } @article {pmid40869205, year = {2025}, author = {Lewandowski, D and Konieczny, M and Różycka, A and Chrzanowski, K and Owecki, W and Kalinowski, J and Stepura, M and Jagodziński, P and Dorszewska, J}, title = {Cathepsins in Neurological Diseases.}, journal = {International journal of molecular sciences}, volume = {26}, number = {16}, pages = {}, doi = {10.3390/ijms26167886}, pmid = {40869205}, issn = {1422-0067}, mesh = {Humans ; *Cathepsins/metabolism ; Animals ; *Nervous System Diseases/metabolism/pathology ; Lysosomes/metabolism ; Biomarkers/metabolism ; }, abstract = {Cathepsins, a family of lysosomal proteases, play critical roles in maintaining cellular homeostasis through protein degradation and modulation of immune responses. In the central nervous system (CNS), their functions extend beyond classical proteolysis, influencing neuroinflammation, synaptic remodeling, and neurodegeneration. Emerging evidence underscores the crucial role of microglial cathepsins in the pathophysiology of several neurological disorders. This review synthesizes current knowledge on the involvement of cathepsins in a spectrum of CNS diseases, including Parkinson's disease, Alzheimer's disease, multiple sclerosis, amyotrophic lateral sclerosis, epilepsy, Huntington's disease, and ischemic stroke. We highlight how specific cathepsins contribute to disease progression by modulating key pathological processes such as α-synuclein and amyloid-β clearance, tau degradation, lysosomal dysfunction, neuroinflammation, and demyelination. Notably, several cathepsins demonstrate both neuroprotective and pathogenic roles depending on disease context and expression levels. Additionally, the balance between cathepsins and their endogenous inhibitors, such as cystatins, emerges as a critical factor in CNS pathology. While cathepsins represent promising biomarkers and therapeutic targets, significant gaps remain in our understanding of their mechanistic roles across diseases. Future studies focusing on their regulation, substrate specificity, and interplay with genetic and epigenetic factors may yield novel strategies for early diagnosis and disease-modifying treatments in neurology.}, } @article {pmid40868609, year = {2025}, author = {Lisiecka, D and Dyson, N and Malpress, K and Smith, A and McNeice, E and Shack, P and Hutchinson, K}, title = {'Finally, in Hands I Can Trust': Perspectives on Trust in Motor Neurone Disease Care.}, journal = {Healthcare (Basel, Switzerland)}, volume = {13}, number = {16}, pages = {}, doi = {10.3390/healthcare13161994}, pmid = {40868609}, issn = {2227-9032}, abstract = {Integrated multidisciplinary care is recognised as essential for people living with motor neurone disease (PlwMND) and their families. The values underpinning integrated care, such as person-centredness, respect, empowerment, and co-production, are central to delivering meaningful and comprehensive support. Trust is an essential yet often overlooked element of effective person- and family-centred integrated care, particularly for PlwMND. While specialist multidisciplinary MND clinics represent the benchmark for evidence-based care, many PlwMND and their families depend significantly on local and community-based support services to maintain quality of life. Trust directly influences their engagement with these services and the continuity of care provided. Trust enables understanding of personal priorities and how they change as the disease progresses, ultimately allowing for person-centred care to happen. Trust is necessary to enable service co-production, which is a strong value of integrated care. Research highlights seven key domains of support essential to PlwMND and their carers: practical, social, informational, psychological, physical, emotional, and spiritual. Effective integrated care requires strong relationships built upon trust, shared decision-making, respect for individuality, and clear communication. Furthermore, due to the rapidly progressive nature of MND, care priorities and perceived symptom burdens may shift significantly over short periods, making flexible, temporally sensitive approaches critical. A dynamic, inclusive model of decision-making that fosters autonomy within and regular co-review of needs is recommended. This perspective paper examines how person- and family-centred integrated care is currently being delivered, what is working well, and how these practices can be further strengthened to enhance the care experiences of PlwMND, their families, and the health and social care providers involved. This paper builds on both theoretical knowledge and clinical experience to offer our perspective on the critical role of trust in co-producing integrated care for PlwMND. It brings together the voices of clinicians and researchers, alongside those with lived experience of MND. We propose a diagram of care that embeds the core values of integrated, person-centred care within the specific context of MND. Our aim is to enhance collaborative practices, strengthen cross-sector partnerships, and ultimately improve the care experiences for professionals, PlwMND, and their families.}, } @article {pmid40868276, year = {2025}, author = {Voicu, V and Toader, C and Șerban, M and Covache-Busuioc, RA and Ciurea, AV}, title = {Systemic Neurodegeneration and Brain Aging: Multi-Omics Disintegration, Proteostatic Collapse, and Network Failure Across the CNS.}, journal = {Biomedicines}, volume = {13}, number = {8}, pages = {}, doi = {10.3390/biomedicines13082025}, pmid = {40868276}, issn = {2227-9059}, abstract = {Neurodegeneration is increasingly recognized not as a linear trajectory of protein accumulation, but as a multidimensional collapse of biological organization-spanning intracellular signaling, transcriptional identity, proteostatic integrity, organelle communication, and network-level computation. This review intends to synthesize emerging frameworks that reposition neurodegenerative diseases (ND) as progressive breakdowns of interpretive cellular logic, rather than mere terminal consequences of protein aggregation or synaptic attrition. The discussion aims to provide a detailed mapping of how critical signaling pathways-including PI3K-AKT-mTOR, MAPK, Wnt/β-catenin, and integrated stress response cascades-undergo spatial and temporal disintegration. Special attention is directed toward the roles of RNA-binding proteins (e.g., TDP-43, FUS, ELAVL2), m6A epitranscriptomic modifiers (METTL3, YTHDF1, IGF2BP1), and non-canonical post-translational modifications (SUMOylation, crotonylation) in disrupting translation fidelity, proteostasis, and subcellular targeting. At the organelle level, the review seeks to highlight how the failure of ribosome-associated quality control (RQC), autophagosome-lysosome fusion machinery (STX17, SNAP29), and mitochondrial import/export systems (TIM/TOM complexes) generates cumulative stress and impairs neuronal triage. These dysfunctions are compounded by mitochondrial protease overload (LONP1, CLPP), UPR maladaptation, and phase-transitioned stress granules that sequester nucleocytoplasmic transport proteins and ribosomal subunits, especially in ALS and FTD contexts. Synaptic disassembly is treated not only as a downstream event, but as an early tipping point, driven by impaired PSD scaffolding, aberrant endosomal recycling (Rab5, Rab11), complement-mediated pruning (C1q/C3-CR3 axis), and excitatory-inhibitory imbalance linked to parvalbumin interneuron decay. Using insights from single-cell and spatial transcriptomics, the review illustrates how regional vulnerability to proteostatic and metabolic stress converges with signaling noise to produce entropic attractor collapse within core networks such as the DMN, SN, and FPCN. By framing neurodegeneration as an active loss of cellular and network "meaning-making"-a collapse of coordinated signal interpretation, triage prioritization, and adaptive response-the review aims to support a more integrative conceptual model. In this context, therapeutic direction may shift from damage containment toward restoring high-dimensional neuronal agency, via strategies that include the following elements: reprogrammable proteome-targeting agents (e.g., PROTACs), engineered autophagy adaptors, CRISPR-based BDNF enhancers, mitochondrial gatekeeping stabilizers, and glial-exosome neuroengineering. This synthesis intends to offer a translational scaffold for viewing neurodegeneration as not only a disorder of accumulation but as a systems-level failure of cellular reasoning-a perspective that may inform future efforts in resilience-based intervention and precision neurorestoration.}, } @article {pmid40868211, year = {2025}, author = {Flor, J and Silveira, AT and Martins, IA and Otero, LB and Silva, FM and Vizuete, AFK and Wink, MR and Rigatto, K}, title = {Biological Actions of Alamandine: A Scoping Review.}, journal = {Biomedicines}, volume = {13}, number = {8}, pages = {}, doi = {10.3390/biomedicines13081957}, pmid = {40868211}, issn = {2227-9059}, abstract = {Objective: This scoping review aims to comprehensively map the existing literature on the mechanisms of action of Alamandine (ALA), a peptide within the renin-angiotensin system, and its effects across various physiological systems. Materials and Methods: Utilizing the Joanna Briggs Institute methodology, a thorough search of databases including PubMed, Embase, Scopus, and Web of Science was conducted up to 30 January 2025. The review focused on identifying studies that explore the biological and therapeutic roles of ALA in different contexts, incorporating in vivo, in vitro, and in silico research. Results: A total of 590 records were initially identified, with 25 meeting the eligibility criteria for inclusion in this review. China emerged as the leading contributor to the research in this area, with a significant focus on the cardiovascular system. The studies revealed that ALA exhibits a range of beneficial effects, including anti-inflammatory, vasodilatory, antifibrotic, and antiapoptotic actions. These effects are primarily mediated through the inhibition of the mitogen-activated protein kinase (MAPK) signaling pathway and modulation of the nitric oxide pathway. The review also highlighted AL's potential in mitigating oxidative stress and its implications in treating cardiovascular diseases, fibrosis, and cancer. Conclusions: The findings suggest that ALA holds significant therapeutic potential, offering antihypertensive, anti-inflammatory, antifibrotic, and anticancer benefits without notable adverse effects, warranting further research to explore its full potential and mechanism of action.}, } @article {pmid40866928, year = {2025}, author = {Tsang, VSK and Malaspina, A and Henson, SM}, title = {The metabolic intersection between immunosenescence and neuroinflammation in amyotrophic lateral sclerosis.}, journal = {Journal of inflammation (London, England)}, volume = {22}, number = {1}, pages = {36}, pmid = {40866928}, issn = {1476-9255}, support = {BBX009610/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the progressive loss of motor neurons. Although it is traditionally viewed as a neuron-centric disease, neurodegeneration is increasingly linked to immunosenescence and age-related immune dysfunction, but the mechanisms connecting immune ageing to neurodegeneration remain poorly understood. In this review, we explore how metabolic reprogramming, especially the loss of metabolic plasticity in senescent immune cells, drives neuroinflammation in ALS. Senescent immune cells, including microglia and T cells, exhibit mitochondrial dysfunction, redox imbalance, impaired autophagy, and altered nutrient-sensing pathways that impair their homeostatic and reparative capacities. These cells adopt a metabolically demanding pro-inflammatory phenotype, sustaining an inflammatory secretome while promoting glial activation and neuronal damage. Finally, we discuss how targeting immunometabolic pathways may offer new therapeutic opportunities to restore immune balance, mitigate neuroinflammation, and potentially slow ALS progression. Understanding the metabolic basis of immune ageing is essential for developing effective, age-tailored interventions for ALS.}, } @article {pmid40866479, year = {2025}, author = {Waheed, ZA and Colagar, AH and Seyedalipour, B and Baziyar, P}, title = {Uncovering the protein aggregation process through effect of G41D mutant SOD1 charge variation in ALS disease.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {31661}, pmid = {40866479}, issn = {2045-2322}, abstract = {Neurodegenerative disorders are a group of hereditary and sporadic conditions that are characterized by progressive nervous system dysfunctions. Mutations in the gene encoding human superoxide dismutase 1 (hSOD1) were among the first to be proposed in line with the protein aggregation theory for ALS disease. This study aimed to characterize the (G41D) mutation/charge effects on the biochemical and biophysical properties of the SOD1 structure through computational and experimental methods. The computed average values of RMSD, RMSF, and Rg demonstrate that mutation results in a loss of conformational stability, increased flexibility, and greater compactness, all supporting the observed aggregation. The G41D mutant revealed distinct changes in β-sheet content compared to WT-SOD1 under amyloidogenic conditions, as confirmed by FTIR spectroscopy. Furthermore, the formation of amyloid/amorphous species was identified using ThT/ANS fluorescence and confirmed by TEM analysis. Mutations that alter the net negative charge of the SOD1 protein are crucial in misfolding and shortening the lag phase in SOD1 aggregation. Our results provide supporting evidence that these charge alterations, alongside amyloid-inducing agents at near-physiological pH, significantly contribute to the formation of amyloid-like species. Therefore, studying the G41D mutation may provide valuable insights into the mechanisms of fALS-associated aggregate formation, which holds promise for the development of highly effective inhibitors in reducing aggregates and therapeutic potential.}, } @article {pmid40865732, year = {2025}, author = {Deighen, MR and Fakult, NJ and Mani, KA and Cullison, CR and Wang, M and Bordeaux, JS and Carroll, BT and Rothermel, LD and Zaorsky, NG}, title = {Response to Sheu et al., "Comments on Fakult et al.'s 'Epidemiology of Merkel Cell Carcinoma in the United States'".}, journal = {Journal of the American Academy of Dermatology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jaad.2025.08.055}, pmid = {40865732}, issn = {1097-6787}, } @article {pmid40865726, year = {2025}, author = {Li, Y and Wang, Y and Li, Y and Jia, X and Du, X}, title = {[Response][to][Pavlović] '[s] "[Response][to][Li][et][al.'s] '[Therapeutic efficacy of platelet-rich plasma combining with microneedling and topical minoxidil in refractory severe androgenic alopecia]'".}, journal = {Journal of the American Academy of Dermatology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jaad.2025.08.056}, pmid = {40865726}, issn = {1097-6787}, } @article {pmid40865585, year = {2025}, author = {Xu, C and Naudet, F and Kim, TT and Hengartner, MP and Horowitz, MA and Kirsch, I and Moncrieff, J and Pigott, E and Plöderl, M}, title = {Large responses to antidepressants or methodological artifacts? A secondary analysis of STAR*D, a single-arm, open-label, non-industry antidepressant trial.}, journal = {Journal of clinical epidemiology}, volume = {}, number = {}, pages = {111943}, doi = {10.1016/j.jclinepi.2025.111943}, pmid = {40865585}, issn = {1878-5921}, abstract = {OBJECTIVES: To replicate Stone et al.'s (2022) [1] finding that the distribution of response in clinical antidepressant trials is trimodal with large, medium-effect, and small subgroups.

METHODS: To apply finite mixture modeling to pre-post Hamilton Depression Rating Scale (HDRS) differences (n = 2184) of STAR*D study's level 1, a single-arm, open-label study. For a successful replication, the best fitting model had to be trimodal, with comparable components as in Stone et al. Secondary/sensitivity analyses repeated the analysis for different baseline levels of depression severity, imputed values, and patient-reported depression symptoms.

RESULTS: The best fitting models were either bimodal or trimodal but the trimodal solution did not meet criteria for replication. The bimodal model had one component with HDRS mean change of M = -13.0, SD = 6.7 and included 65.3% of patients, and another component with M = -1.8, SD = 5.1, 34.7%, respectively. For the trimodal model, the component with the largest change (M = -14.3, SD = 6.4) applied to 52% of patients, which differed substantially from the large effect component in Stone et al. (M = -18.8, SD = 5.1) which applied to 7.2%. Secondary/sensitivity analyses arrived at similar conclusions and for patient-reported depression symptoms the best fitting models were unimodal or bimodal.

CONCLUSIONS: This analysis failed to identify the trimodal distribution of response reported in Stone et al. In addition to being difficult to operationalize for regulatory purposes, results from mixture modeling are not sufficiently reliable to replace the more robust approach of comparing mean differences in depression rating scale scores between treatment arms.}, } @article {pmid40865525, year = {2025}, author = {McEachin, ZT and Chung, M and Stratton, SA and Han, C and Kim, WJ and Sheth, U and Thomas, EV and Issenberg, E and Kamra, T and Merino, P and Levites, Y and Raj, N and Dammer, EB and Duong, DM and Ping, L and Shantaraman, A and Trautwig, AN and Gadhavi, J and Assefa, E and Gearing, M and Kelly, KM and Roemer, SF and DeTure, M and Asress, S and Kukar, T and Fournier, C and Dickson, DW and Petrucelli, L and Golde, TE and Oskarsson, B and Gendron, TF and Seyfried, NT and Glass, JD}, title = {Molecular impact of antisense oligonucleotide therapy in C9orf72-associated ALS.}, journal = {Cell}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.cell.2025.07.045}, pmid = {40865525}, issn = {1097-4172}, abstract = {C9orf72-associated amyotrophic lateral sclerosis (c9ALS) is caused by an intronic G4C2 repeat expansion that leads to toxic RNA transcripts and dipeptide repeat proteins (DPRs). A clinical trial using the antisense oligonucleotide (ASO) BIIB078 to target these transcripts was discontinued after failing to provide clinical benefit. Here, we determine the extent of target engagement in the central nervous system (CNS) and elucidate pharmacodynamic cerebrospinal fluid (CSF) biomarkers following treatment. CSF from BIIB078-treated cases showed reduced DPRs and sustained increases in inflammatory biomarkers, including C-C motif chemokine ligand 26 (CCL26). BIIB078 was widely distributed in postmortem CNS tissue; however, DPRs and phosphorylated TDP-43 remained abundant. Proteomic signatures in c9ALS spinal cord were not altered with treatment, although a distinct increase in RNase T2 abundance that correlated with BIIB078 concentration was observed. Thus, despite widespread distribution, BIIB078 did not significantly impact key CNS pathologies, emphasizing the need to identify pharmacodynamic biomarkers that reflect disease-relevant neuropathological changes in response to ASO therapies.}, } @article {pmid40864790, year = {2025}, author = {Du, Y and Fan, SS and Wu, H and He, J and He, Y and Meng, XY and Xu, X}, title = {Convergent and Divergent Mitochondrial Pathways as Causal Drivers and Therapeutic Targets in Neurological Disorders.}, journal = {Current issues in molecular biology}, volume = {47}, number = {8}, pages = {}, doi = {10.3390/cimb47080636}, pmid = {40864790}, issn = {1467-3045}, support = {0801059201//the Research Fund for the Doctoral Program of Anhui Medical University/ ; 82303057//National Natural Science Foundation of China/ ; 2023AFB521//Natural Science Foundation of Hubei Province of China/ ; }, abstract = {Mitochondrial dysfunction is implicated across a spectrum of neurological diseases, yet its causal role and mechanistic specificity remain unclear. This study employed a multi-modal integrative analysis of mitochondrial gene expression in Alzheimer's Disease (AD), Amyotrophic Lateral Sclerosis (ALS), Multiple Sclerosis (MS), and Parkinson's Disease (PD) to address these gaps. We combined machine learning for predictive modeling with genetic causal inference methods (Mendelian Randomization, colocalization, PheWAS), followed by drug enrichment analysis and molecular docking. Our machine learning models, particularly Support Vector Machine and Multi-layer Perceptron, effectively classified these conditions, with MS exhibiting the highest predictability (mean Accuracy: 0.758). Causal inference analyses identified specific gene-disease links; for instance, genetically predicted increased expression of PDK1 was causally associated with an elevated risk for both AD (OR = 1.041) and ALS (OR = 1.037), identifying pyruvate metabolism as a shared vulnerability. In contrast, genes like SLC25A38 emerged as highly predictive specifically for PD. We also observed evidence of potential brain-periphery interaction, such as a bidirectional causal relationship between red blood cell indices and MS risk. Finally, drug enrichment analysis highlighted Celecoxib, and subsequent molecular docking predicted a strong binding affinity to PDK1 (docking score S = -6.522 kcal/mol), generating hypotheses for potential metabolic modulation. Taken together, this study provides a computational hypothesis framework suggesting mitochondrial pathways and targets that warrant future biological validation. This study provides specific, genetically supported evidence for the causal role of mitochondrial pathways in neurological diseases and identifies tangible targets for future therapeutic development.}, } @article {pmid40864664, year = {2025}, author = {Popoli, R and Wells, TL and Akay, T}, title = {Unlocking new mechanisms for future ALS therapies: early interventions with cholinergic antagonists reduce neuromuscular decline.}, journal = {Journal of neurophysiology}, volume = {}, number = {}, pages = {}, doi = {10.1152/jn.00306.2025}, pmid = {40864664}, issn = {1522-1598}, support = {2017//ALS Society of Canada (ALS Canada)/ ; 162357//Canadian Government | Canadian Institutes of Health Research (CIHR)/ ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative condition characterized by motor neuron loss, leading to muscle paralysis and death. C-boutons have been shown to be part of the compensatory mechanism behind delayed symptom onset, and are most active during vigorous exercises, like swimming. When mutant mice with silenced C-boutons perform this exercise, disease progression and behavioral performance drastically improve. Genetic manipulation of C-boutons in human patients remains limited, therefore, we sought to manipulate these synapses using cholinergic antagonists in the presence and absence of exercise in a mouse model of ALS. We demonstrate that atropine and methoctramine administration yield significant improvements in human endpoints, weight maintenance, treadmill performance, and grip strength. Most remarkably, muscle innervation was greatly enhanced at humane endpoints compared to controls, suggesting these drugs provide a protective effect against loss of motor control. We found that methoctramine provided greater benefits in the absence of exercise, hinting at the presence of novel cholinergic mechanisms that can be manipulated in order to preserve motor function. Moreover, we provide evidence that these results are independent of C-boutons, and that methoctramine does not appear to cross the blood-brain barrier. Our results reveal pharmacological mechanisms by which muscle denervation can be reduced, thereby decreasing the rate of disease progression. We have uncovered a promising avenue for improving ALS symptoms by pharmacologically manipulating cholinergic transmission. This mechanism presents as a possible therapy translatable to the clinical setting, which has the potential to prevent the loss of motor control in patients with ALS.}, } @article {pmid40864229, year = {2025}, author = {Xu, Y and Raban, MZ and Li, L and Nguyen, AD and Silva, SSM and Huang, G and Arnolda, G and Westbrook, JI and Wabe, N}, title = {Anticholinergic medication use and falls in Australian residential aged care: a retrospective multisite cohort study.}, journal = {Aging clinical and experimental research}, volume = {37}, number = {1}, pages = {257}, pmid = {40864229}, issn = {1720-8319}, support = {APP1170898//Australian National Health and Medical Research Council/ ; APP1170898//Australian National Health and Medical Research Council/ ; }, mesh = {Humans ; *Accidental Falls/statistics & numerical data/prevention & control ; *Cholinergic Antagonists/adverse effects/therapeutic use ; Female ; Male ; Aged ; Retrospective Studies ; Aged, 80 and over ; *Homes for the Aged/statistics & numerical data ; Australia ; New South Wales ; }, abstract = {BACKGROUND: Associations between anticholinergic load and falls remain understudied in residential aged care facilities (RACFs).

AIMS: To examine associations between anticholinergic load and falls in the first year after entry to an RACF.

METHODS: We aggregated routinely collected data from 27 RACFs in New South Wales, Australia. Anticholinergic load and falls were repeatedly measured for one year after residents first entered an RACF. Thirteen 28-day review periods were set. Associations between anticholinergic load in a review period and any falls in the next review period were examined, comprising 12 repeated measurements of associations. We included new residents aged ≥ 65 years, who entered an RACF between 1 July 2014 and 2 September 2021. Six scales were used: Anticholinergic Cognitive Burden (ACB), Anticholinergic Drug Scale (ADS), Anticholinergic Loading Scale (ALS), Anticholinergic Risk Scale (ARS), Chew's list, and Clinician-rated Anticholinergic Score (CrAS). We used mixed-effect logistic regression models, adjusting for potential confounders. Facility was used as a cluster variable.

RESULTS: For the 2300 residents (67.7% females), there were steady increases in mean anticholinergic load from the first to the 12th review period. Per one-point higher anticholinergic load was associated with an increased risk of falls, adjusted odds ratios: 1.08 (95% confidence interval[CI] 1.04, 1.12) using ACB, 1.11 (95%CI 1.06, 1.15) using ADS, 1.15 (95%CI 1.10, 1.21) using ALS, 1.10 (95%CI 1.04, 1.17) using ARS, 1.18 (95%CI 1.09, 1.27) using Chew's list, and 1.14 (95%CI 1.10, 1.19) using CrAS.

CONCLUSION: Anticholinergic scales may be useful to inform falls prevention programs for new RACF residents.}, } @article {pmid40864161, year = {2025}, author = {Zhu, Y and Cho, K and Lacin, H and Zhu, Y and DiPaola, JT and Wilson, BA and Patti, G and Skeath, JB}, title = {Loss of dihydroceramide desaturase drives neurodegeneration by disrupting endoplasmic reticulum and lipid droplet homeostasis in glial cells.}, journal = {eLife}, volume = {13}, number = {}, pages = {}, pmid = {40864161}, issn = {2050-084X}, support = {NS036570/NS/NINDS NIH HHS/United States ; NS122903/NS/NINDS NIH HHS/United States ; ES2028365/ES/NIEHS NIH HHS/United States ; }, mesh = {Animals ; *Endoplasmic Reticulum/metabolism ; *Neuroglia/metabolism/pathology ; *Lipid Droplets/metabolism ; *Oxidoreductases/metabolism/genetics ; Homeostasis ; *Drosophila Proteins/metabolism/genetics ; Ceramides/metabolism ; *Drosophila melanogaster/genetics ; }, abstract = {Dihydroceramide desaturases convert dihydroceramides to ceramides, the precursors of all complex sphingolipids. Reduction of DEGS1 dihydroceramide desaturase function causes pediatric neurodegenerative disorder hypomyelinating leukodystrophy-18 (HLD-18). We discovered that infertile crescent (ifc), the Drosophila DEGS1 homolog, is expressed primarily in glial cells to promote CNS development by guarding against neurodegeneration. Loss of ifc causes massive dihydroceramide accumulation and severe morphological defects in cortex glia, including endoplasmic reticulum (ER) expansion, failure of neuronal ensheathment, and lipid droplet depletion. RNAi knockdown of the upstream ceramide synthase schlank in glia of ifc mutants rescues ER expansion, suggesting dihydroceramide accumulation in the ER drives this phenotype. RNAi knockdown of ifc in glia but not neurons drives neuronal cell death, suggesting that ifc function in glia promotes neuronal survival. Our work identifies glia as the primary site of disease progression in HLD-18 and may inform on juvenile forms of ALS, which also feature elevated dihydroceramide levels.}, } @article {pmid40863128, year = {2025}, author = {Pawłowska, M and Kruszka, J and Porzych, M and Garbarek, J and Nuszkiewicz, J}, title = {Ketogenic Metabolism in Neurodegenerative Diseases: Mechanisms of Action and Therapeutic Potential.}, journal = {Metabolites}, volume = {15}, number = {8}, pages = {}, pmid = {40863128}, issn = {2218-1989}, abstract = {Neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis, are characterized by progressive neuronal loss and share key pathological features such as oxidative stress, mitochondrial dysfunction, and chronic neuroinflammation. Recent research has highlighted the potential of ketogenic metabolism, particularly the use of ketone bodies like β-hydroxybutyrate, as a therapeutic approach targeting these shared mechanisms. This review provides a comprehensive synthesis of current knowledge on the neuroprotective effects of ketogenic interventions, including both dietary strategies and exogenous ketone supplementation. We discuss how ketone bodies improve mitochondrial function, reduce reactive oxygen species, modulate inflammatory pathways, and influence neurotransmission and synaptic plasticity. Additionally, we examine experimental and clinical evidence supporting the application of ketogenic therapies in neurodegenerative diseases, highlighting disease-specific findings, benefits, and limitations. While preclinical data are robust and suggest meaningful therapeutic potential, clinical studies remain limited and heterogeneous, with challenges related to adherence, safety, and patient selection. The review also addresses the translational relevance of ketogenic strategies, considering their feasibility, combination with other therapies, and the need for personalized approaches based on genetic and metabolic profiles. By critically evaluating existing data, this article aims to clarify the mechanisms through which ketogenic metabolism may exert neuroprotective effects and to outline future directions for research and clinical application in the context of neurodegenerative disorders.}, } @article {pmid40862353, year = {2025}, author = {Harji, ZA and Rampal, CJ and Rodríguez, EC and Petel Légaré, V and Lissouba, A and Semmler, S and Liao, M and Ross, JP and Rouleau, GA and Vande Velde, C and Armstrong, GAB}, title = {TARDBP (TDP-43) Knock-in Zebrafish Display a Late-Onset Motor Phenotype and Loss of Large Spinal Cord Motor Neurons.}, journal = {Annals of neurology}, volume = {}, number = {}, pages = {}, doi = {10.1002/ana.78012}, pmid = {40862353}, issn = {1531-8249}, support = {/CAPMC/CIHR/Canada ; //ALS Society of Canada/ ; //Weston Family Foundation/ ; //Fonds de Recherche du Québec/ ; }, abstract = {OBJECTIVE: Mutations in TARDBP (encoding TDP-43) are associated with the neurodegenerative disease amyotrophic lateral sclerosis (ALS) and include familial missense mutations where there are a lack of models and mechanisms examining how they are pathogenic.

METHODS: In this study, we developed 2 tardbp (Tdp-43) knock-in (KI) zebrafish mutant models encoding the analogous A382T and G348C variants and investigated their degenerative phenotypes.

RESULTS: We show that both models display reduced survival as well as an age-dependent motor phenotype that manifests at 1.5 years. Both variants in either the heterozygous or homozygous state did not impact protein expression levels of Tdp-43 in the central nervous system. However, homozygous G347C zebrafish displayed reduced expression levels of the tardbp transcript. We observed muscle cell atrophy starting at 1 year of age and loss of large spinal cord motor neurons in both KI models in older fish (2.35-3 years of age). We did not observe Tdp-43 aggregates. However, we did observe increased cytoplasmic Tdp-43 localization in spinal cord motor neurons in A379T zebrafish. At 1 year of age, whole spinal cord RNA-sequencing revealed an upregulation of neuroinflammatory transcripts in both models, as well as the selective downregulation of transcripts involved with synaptic function in G347C zebrafish, including syn2a, syn2b, syt2a, and stxbp1a.

INTERPRETATION: These novel models of common TDP-43 disease variants provide a unique opportunity to further our understanding of neurodegeneration in vivo and demonstrate that mutations in the same protein and domain can manifest with different phenotypes. ANN NEUROL 2025.}, } @article {pmid40861195, year = {2025}, author = {Chapman, LR and Shepheard, S and Verber, N and Turner, MR and Malaspina, A and Rogers, ML and Shaw, PJ}, title = {Urinary P75: a promising biomarker for amyotrophic lateral sclerosis.}, journal = {BMJ neurology open}, volume = {7}, number = {2}, pages = {e001088}, pmid = {40861195}, issn = {2632-6140}, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive and fatal disease. The urinary neurotrophin receptor p75 extracellular domain (p75[ECD]) has previously been reported as a potential disease biomarker for diagnosis, severity assessment and monitoring therapeutic response.

METHODS: This study measured urinary p75[ECD] using an enzyme-linked immunoassay and normalised the results against urinary creatinine. Participants were recruited via A Multicentre Biomarker Resource Strategy in ALS (AMBroSIA) programme. Study participants included 97 ALS patients, 24 of whom were studied longitudinally, and 27 healthy controls. The study focused on urinary p75[ECD] and its potential association with different subtypes of ALS, change over time, disease progression, severity of symptoms and survival from symptom onset.

RESULTS: Confirming previous findings, urinary p75[ECD] levels were significantly higher in patients with ALS (median 6.78 ng/mg, 95% CI (5.12 to 9.23)) compared with controls (4.57 ng/mg, 95% CI (3.35 to 5.89)) at first study visit. There was a significant negative correlation between absolute change in the Revised ALS Functional Rating Scale score and p75[ECD] levels (Spearman's rho=-0.371, p≤0.0004, 95% CI (-0.543 to -0.169)), indicating that an increase in the severity of motor neuron injury correlated with an increase in p75[ECD] levels. There was a significant increase in p75[ECD] between first and second samples in the same participants, indicating an increase in the level of this biomarker longitudinally during the disease course (moderate effect size of -0.3).

CONCLUSIONS: Urinary p75[ECD] is a promising candidate as a biomarker, which increases with disease progression and has the potential to serve as a pharmacodynamic biomarker.}, } @article {pmid40860154, year = {2025}, author = {Li, D and Wei, Y and Yang, R and Luo, X and Liu, Y and Zhao, W and Yang, H and Wu, Y and Wang, Y and Huang, Z}, title = {An unrecognized mechanism of self-protection in degenerating neurons mediated by astrocytic YAP through Wnts/β-catenin/EAAT2 signaling in C9orf72-poly-GA mice.}, journal = {Theranostics}, volume = {15}, number = {16}, pages = {8176-8201}, pmid = {40860154}, issn = {1838-7640}, mesh = {Animals ; *Astrocytes/metabolism/pathology ; *Amyotrophic Lateral Sclerosis/metabolism/pathology/genetics ; YAP-Signaling Proteins ; Mice ; Disease Models, Animal ; *C9orf72 Protein/genetics/metabolism ; Mice, Knockout ; *Excitatory Amino Acid Transporter 2/metabolism ; *Cell Cycle Proteins/metabolism ; *Adaptor Proteins, Signal Transducing/metabolism/genetics ; beta Catenin/metabolism ; Motor Neurons/metabolism/pathology ; *Wnt Signaling Pathway ; Neurons/metabolism ; Humans ; Signal Transduction ; }, abstract = {Rationale: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by the progressive loss of motor neurons in the central nervous system (CNS). Non-neuronal cells, particularly astrocytes, have been recognized as pivotal contributors to ALS onset and progression. However, the underlying mechanisms of interactions between astrocytes and motor neurons during ALS remain unclear. Recent studies have identified the neuronal Hippo kinase mammalian sterile 20-like kinase 1 (MST1) as a key regulator of neurodegeneration in ALS. Yes-associated protein (YAP), a major downstream effector of the Hippo pathway, is predominantly expressed in astrocytes. However, the role of astrocytic YAP in ALS and its underlying mechanisms remain unexplored. Methods: To evaluate the function of YAP in ALS, we established a C9orf72-poly-GA mouse model (ALS mice) via intracerebroventricular injection of AAV viruses. Furthermore, mice with conditional knockout (CKO) of YAP in astrocytes (YAP[GFAP]-CKO mice) were generated and then YAP[GFAP]-CKO ALS mice and their littermate controls (YAP[f/f] ALS mice) were used as experimental subjects. Behavioral tests, immunostaining, Nissl staining, quantitative real-time PCR (qPCR), and Western blotting were used to assess the effects of astrocytic YAP deletion in ALS progression. In addition, we investigated the role and mechanism of astrocytic YAP in the pathogenesis of ALS by integrating RNA sequencing (RNA-seq) from primary cultured astrocytes with single-nucleus transcriptomic (snRNA-seq) from C9orf72-ALS/FTD patients. Then, in vitro experiments including primary cultured astrocytes and neurons were used to further elucidate the potential molecular mechanism of astrocytic YAP in ALS. Finally, we evaluated the therapeutic effects of the excitatory amino acid transporter-2 (EAAT2) activator LDN-212320 and the Hippo kinase MST1/2 inhibitor XMU-MP-1 as candidate treatments for ALS. Results: We found that YAP was upregulated and activated specifically in astrocytes, but not in neurons or microglia, within the motor cortex of ALS mice. Conditional knockout of YAP in astrocytes exacerbated motor deficits, neuronal loss, pathological translocation of TDP-43, inflammatory infiltration, and reduced astrocytic proliferation in ALS mice. Mechanistically, Wnts secreted by degenerating neurons and astrocytes activated YAP/β-catenin signaling and further promoted the expression of EAAT2 in astrocytes, which prevented neuronal glutamate excitotoxicity, neuronal loss, and motor dysfunction in ALS mice. Interestingly, treatment with LDN-212320 promoted EAAT2 expression and partially restored motor deficits and neuronal loss in YAP[GFAP]-CKO ALS mice. Finally, activation of YAP by XMU-MP-1 upregulated β-catenin and EAAT2 expression, and partially alleviated motor deficits and neurodegeneration in ALS mice. Conclusions: These results identify an unrecognized mechanism of self-protection in degenerating neurons mediated by astrocytic YAP through Wnts/β-catenin/EAAT2 signaling to prevent glutamate excitotoxicity of neurons in ALS mice, and provide a novel drug target for ALS.}, } @article {pmid40859959, year = {2025}, author = {Mao, S and Qiao, R and Wang, Q and Shen, L and Li, D and Huo, X and Wang, J and Liu, K and Chen, W and Zhu, T and Zhang, B and Leng, S and Bai, Y}, title = {Activity and Heterogeneity of Astrocytes in Neurological Diseases: Molecular Mechanisms and Therapeutic Targets.}, journal = {MedComm}, volume = {6}, number = {9}, pages = {e70329}, pmid = {40859959}, issn = {2688-2663}, abstract = {Astrocytes, the most prevalent glial cells in the central nervous system (CNS), play crucial roles in maintaining CNS homeostasis and responding to various pathological stimuli. They play key roles in neural development, neurotransmission, neuroinflammation, metabolic support, and tissue repair. Recent advancements in single-cell sequencing have revealed the remarkable heterogeneity of astrocytes, with distinct subpopulations differentially contributing to disease progression in neurological disorders, including Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, ischemic stroke, intracerebral hemorrhage, and multiple sclerosis. In addition, they play an important role in various behavioral neuropsychiatric disorders. This review highlights the dual roles of astrocytes in disease progression, driven by their diverse molecular profiles and functions. It outlines the key molecular mechanisms underlying astrocyte heterogeneity and their impact on neuroinflammation, neuronal support, and ionic balance regulation. Additionally, the review discusses potential therapeutic strategies targeting astrocytes to modulate these processes, aiming to improve treatment outcomes in neurological diseases. By elucidating the specific roles of astrocyte subsets in disease, this review seeks to advance the development of precision medicine for astrocyte-related neurological disorders.}, } @article {pmid40859014, year = {2025}, author = {Zhang, MY and Ma, Y and Wang, LQ and Xia, W and Li, XN and Zhao, K and Chen, J and Li, D and Zou, L and Wang, Z and Liu, C and Liang, Y}, title = {Distinct amyloid fibril structures formed by ALS-causing SOD1 mutants G93A and D101N.}, journal = {EMBO reports}, volume = {}, number = {}, pages = {}, pmid = {40859014}, issn = {1469-3178}, support = {32271326//MOST | National Natural Science Foundation of China (NSFC)/ ; 32201040//MOST | National Natural Science Foundation of China (NSFC)/ ; 32071212//MOST | National Natural Science Foundation of China (NSFC)/ ; 22425704//MOST | National Natural Science Foundation of China (NSFC)/ ; 82188101//MOST | National Natural Science Foundation of China (NSFC)/ ; 12272276//MOST | National Natural Science Foundation of China (NSFC)/ ; 2024YFA1307301//MOST | National Key Research and Development Program of China (NKPs)/ ; 2023ZD0507202//National Science and Technology Major Project ()/ ; 2021TQ0252//China Postdoctoral Science Foundation (China Postdoctoral Foundation Project)/ ; 2021M700103//China Postdoctoral Science Foundation (China Postdoctoral Foundation Project)/ ; JCYJ20200109144418639//| Science and Technology Planning Project of Shenzen Municipality (Science and Technology Planning Project of Shenzhen of China)/ ; }, abstract = {Two hundred eight genetic mutations in SOD1 have been linked to amyotrophic lateral sclerosis (ALS). Of these, the G93A and D101N variants maintain much of their physiological function, closely resembling that of wild-type SOD1, and the SOD1-G93A transgenic mouse is the most extensively used mouse line in the study of ALS. In this study, we report two cryo-EM structures of amyloid fibrils formed by G93A and D101N mutants of SOD1 protein. These mutations give rise to amyloid fibrils with distinct structures compared to native SOD1 fibrils. The fibril core displays a serpentine configuration featuring four β-strands, held together by two hydrophobic cavities and a salt bridge between Arg143 and Asp96 in the G93A fibril, and by a hydrophobic cavity and a salt bridge between Arg143 and Asp132 in the D101N fibril, demonstrating unique structural features for each mutant. Moreover, our results show that G93A fibrils are significantly more toxic than those formed by D101N, which do not show a marked increase in toxicity compared to wild-type SOD1 fibrils. This study sheds light on the structural mechanisms through which SOD1 mutants aggregate and induce cytotoxicity in ALS.}, } @article {pmid40858858, year = {2025}, author = {Loo, YS and Yusoh, NA and Yap, K and Ng, CS}, title = {Programmable self-replicating JEV nanotherapeutics redefine RNA delivery in ALS.}, journal = {Communications biology}, volume = {8}, number = {1}, pages = {1282}, doi = {10.1038/s42003-025-08579-7}, pmid = {40858858}, issn = {2399-3642}, support = {PM010CNI000148//International Brain Research Organization (IBRO)/ ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive motor neuron degeneration, leading to paralysis and respiratory failure. Current therapies offer limited benefits, highlighting the need for novel therapeutic strategies. Antisense oligonucleotides (ASO) and CRISPR/Cas9 gene editing hold promise, but their effective delivery to the central nervous system (CNS) remains a significant challenge. Here, a potential approach involves utilizing engineered Japanese encephalitis virus (JEV) as a self-replicating nanocarrier for targeted ASO delivery to motor neurons. By leveraging JEV's natural neurotropism and "Trojan horse" mechanism of immune cell-mediated CNS entry, this strategy overcomes the blood-brain and blood-spinal cord barriers (BBB/BSCB). Incorporation of ASO sequences within the JEV genome facilitates co-packaging and sustained therapeutic delivery, while microRNA (miRNA)-mediated attenuation may enhance safety and CNS specificity. This theoretical framework offers a potential paradigm shift in CNS gene therapy for ALS and other neurodegenerative diseases by enabling efficient, targeted, and sustained ASO delivery. However, experimental validation remains critical to assess its safety and therapeutic efficacy.}, } @article {pmid40858618, year = {2025}, author = {Lenoel, I and Ribon, M and Lorenc, F and Diebold, A and Philibert, CE and Robaldo, D and Badsi, M and Perronnet, J and Lameth, J and Berriat, F and Misawa, H and Coutelier, M and Cassel, R and Sarrazin, N and Jost-Mousseau, C and Bohl, D and Millecamps, S and Mallat, M and Brenner, D and Weishaupt, JH and Boillée, S and Lobsiger, CS}, title = {ALS/FTD-linked TBK1 deficiency in microglia induces an aged-like microglial signature and drives social recognition deficits in mice.}, journal = {Nature communications}, volume = {16}, number = {1}, pages = {7951}, pmid = {40858618}, issn = {2041-1723}, abstract = {TANK-Binding Kinase 1 (TBK1) is involved in autophagy and immune signaling. Dominant loss-of-function mutations in TBK1 have been linked to Amyotrophic Lateral Sclerosis (ALS), Fronto-temporal dementia (FTD), and ALS/FTD. However, pathogenic mechanisms remain unclear, particularly the cell-type specific disease contributions of TBK1 mutations. Here, we show that deleting Tbk1 from mouse motor neurons does not induce transcriptional stress, despite lifelong signs of autophagy deregulations. Conversely, Tbk1 deletion in microglia alters their homeostasis and reactive responses. In both spinal cord and brain, Tbk1 deletion leads to a pro-inflammatory, primed microglial signature with features of ageing and neurodegeneration. While it does not induce or modify ALS-like motor neuron damage, microglial Tbk1 deletion is sufficient to cause early FTD-like social recognition deficits. This phenotype is linked to focal microglial activation and T cell infiltration in the substantia nigra pars reticulata and pallidum. Our results reveal that part of TBK1-linked FTD disease originates from microglial dysfunction.}, } @article {pmid40858507, year = {2025}, author = {Barajas, CB and Young, MT and Bustamante, AV and Padilla-Frausto, I and Garcia, RE and Langellier, BA and Roby, DH and Stimpson, JP and Ponce, NA and Eberth, JM and Stehr, M and Ortega, AN}, title = {Organizational Perspectives on the Public Charge Rule and Health Care Access for Latino Immigrants in California.}, journal = {Health services research}, volume = {}, number = {}, pages = {e70032}, doi = {10.1111/1475-6773.70032}, pmid = {40858507}, issn = {1475-6773}, support = {R01MD014146/MD/NIMHD NIH HHS/United States ; R01MD018727/MD/NIMHD NIH HHS/United States ; }, abstract = {OBJECTIVE: To examine how mis- and disinformation about the Public Charge Ground of Inadmissibility final rule ("public charge rule") influences health care access for Latino immigrants in California as seen through the perspectives of leaders in health-serving organizations.

STUDY SETTING AND DESIGN: This qualitative study included semi-structured interviews with healthcare and community-based organizational leaders serving Latino immigrants in California. Viswanath et al.'s structural influence model of communication and equity guided the analyses and interpretation of the findings.

Between May 2024 and April 2025, primary data were collected from 31 organizations, resulting in 32 semi-structured interviews with 38 participants. Interviews were conducted via Zoom and transcribed verbatim. Researchers coded the data based on recurring themes using Dedoose software.

PRINCIPAL FINDINGS: Participants identified the public charge rule as a significant barrier to health care access for Latino immigrants. The policy has discouraged many Latinos from accessing public benefits, particularly the state's Medicaid and Supplemental Nutrition Assistance Program. In addition, immigrants' trusted sources of information (e.g., family, friends, and attorneys) were often misinformed about the policy, which amplified confusion and fear. Organizations respond by providing accurate information and connecting individuals with reliable resources to clarify that using public benefits would not necessarily result in being classified as a public charge. However, most efforts focused on education rather than directly countering mis- and disinformation.

CONCLUSIONS: Healthcare and community-based organizations offer unique perspectives as trusted intermediaries who help Latino immigrant families navigate health care and public benefits. Their close daily interactions reveal how misinformation about the public charge rule deters families from accessing essential services and makes it more challenging for organizations to fulfill their missions. These insights underscore the need for culturally responsive outreach and policy solutions that address information gaps and the climate of fear affecting community health.}, } @article {pmid40858416, year = {2025}, author = {Hao, R and He, C and Cheng, Y and Sang, S and Bai, Y}, title = {A plug-and-play data processing module for complex faults diagnosis.}, journal = {ISA transactions}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.isatra.2025.07.061}, pmid = {40858416}, issn = {1879-2022}, abstract = {Intelligent fault diagnosis technology is a vital approach to detect and sustain contemporary equipment. Although it is widely utilized for equipment monitoring, the limited number of samples available in the industry and complex faults restrict its further development. This paper presents a plug-and-play data processing module to expand the number of samples and improve the internal relationship between them to improve the overall performance of the deep learning model. an Amplitude-phase composite data enhancement (APCUP) method for expanding training samples is designed in the module, which uses Discrete Fourier Transform to randomly fuse multiple fault types in proportion to generate new fault samples, achieving the goal of expanding the training dataset. Based on the interdependence of faults in real scenes, the module also designs an adjacent label smoothing (ALS) strategy to process the original label data, which smoothen the label over, prevents the excessive absolute classification and improves the robustness of the model. The efficacy and viability of the module have been demonstrated through comprehensive experimentation on the cutting-edge industrial robot arm platform and two public datasets. The incorporation of a data processing module has markedly enhanced the model's capacity to diagnose intricate faults. As the module processes the input, there is a significant increase in accuracy and a reduction in errors.}, } @article {pmid40858193, year = {2025}, author = {Wu, Q and Liu, X and Zhang, T and Cui, S and Huang, B and Huang, C and Cao, Q and Xia, XG and Zhou, H}, title = {Astrocytes Expressing Mutant hnRNPA1 Induce Non-cell-autonomous Motor Neuron Death.}, journal = {Brain research bulletin}, volume = {}, number = {}, pages = {111522}, doi = {10.1016/j.brainresbull.2025.111522}, pmid = {40858193}, issn = {1873-2747}, abstract = {Pathogenic mutation of heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) is causative to amyotrophic lateral sclerosis (ALS). Neuron death resulting from pathogenic hnRNPA1 may not require its presence across all pertinent cells types, including neurons, glia, and muscles. Rather, the exclusive presence of pathogenic hnRNPA1 in a specific cell type, such as astrocytes, may suffice to substantially alter cellular functions. Consequently, this alteration initiates abnormal interaction within intricate neuron-glia networks, culminating in non-cell-autonomous motor neuron death. To investigate the pivotal role of non-cell-autonomous neuron death in hnRNPA1-associated ALS, we developed transgenic rats overexpressing mutant hnRNPA1 in specifically astrocytes. The confined overexpression of pathogenic hnRNPA1 in astrocytes instigated a sequence of events resulting in motor neuron death and subsequent muscle atrophy. These findings underscore the critical, non-cell-autonomous contribution of astrocytes to hnRNPA1-induced neurodegeneration in ALS, and point toward astrocytic pathways as potential therapeutic targets.}, } @article {pmid40857498, year = {2025}, author = {Zhao, B and Huggins, JE and Kang, J}, title = {Bayesian Inference on Brain-Computer Interfaces via GLASS.}, journal = {Journal of the American Statistical Association}, volume = {}, number = {}, pages = {}, doi = {10.1080/01621459.2025.2498088}, pmid = {40857498}, issn = {0162-1459}, abstract = {Brain-computer interfaces (BCIs), particularly the P300 BCI, facilitate direct communication between the brain and computers. The fundamental statistical problem in P300 BCIs lies in classifying target and non-target stimuli based on electroencephalogram (EEG) signals. However, the low signal-to-noise ratio (SNR) and complex spatial/temporal correlations of EEG signals present challenges in modeling and computation, especially for individuals with severe physical disabilities-BCI's primary users. To address these challenges, we introduce a novel Gaussian Latent channel model with Sparse time-varying effects (GLASS) under a Bayesian framework. GLASS is built upon a constrained multinomial logistic regression particularly designed for the imbalanced target and non-target stimuli. The novel latent channel decomposition efficiently alleviates strong spatial correlations between EEG channels, while the soft-thresholded Gaussian process (STGP) prior ensures sparse and smooth time-varying effects. We demonstrate GLASS substantially improves BCI's performance in participants with amyotrophic lateral sclerosis (ALS) and identifies important EEG channels (PO8, Oz, PO7, and Pz) in parietal and occipital regions that align with existing literature. For broader accessibility, we develop an efficient gradient-based variational inference (GBVI) algorithm for posterior computation and provide a user-friendly Python module available at https://github.com/BangyaoZhao/GLASS.}, } @article {pmid40857153, year = {2025}, author = {Szewczyk, B and Zimyanin, V and Japtok, J and Held, A and Pal, A and Großmann, D and Glaß, H and Jürs, AV and Dash, BP and Bak, M and Naumann, M and Hartmann, C and Kuksenko, O and Günther, R and Kao, TT and Sameith, K and Dahl, A and Sterneckert, J and Aronica, E and Shneider, NA and Büttner, A and Catanese, A and Phatnani, H and Kipp, M and Wainger, BJ and Goswami, A and Hermann, A}, title = {Activation of polo-like kinase 1 correlates with selective motor neuron vulnerability in familial ALS.}, journal = {Cell reports}, volume = {44}, number = {9}, pages = {116113}, doi = {10.1016/j.celrep.2025.116113}, pmid = {40857153}, issn = {2211-1247}, abstract = {Mutations in the Fused in Sarcoma (FUS) gene cause familial amyotrophic lateral sclerosis (ALS), characterized by selective degeneration of spinal motor neurons (sMNs) with relative sparing of cortical neurons (CNs). The mechanisms underlying this cell-type vulnerability remain unclear. Here, we compare CNs and sMNs derived from FUS-ALS models to assess differential responses to FUS mutations. We find that CNs are less affected than sMNs in DNA damage repair, axonal organelle trafficking, and stress granule dynamics. RNA sequencing (RNA-seq) reveals distinct transcriptomic signatures, with sMNs uniquely activating DNA damage responses involving cell cycle regulators, particularly polo-like kinase 1 (PLK1). PLK1 is highly expressed in sMNs but not CNs, correlating with greater nuclear FUS loss and splicing defects in sMNs. Cross-comparison with other familial ALS RNA-seq datasets highlights PLK1 upregulation as a shared molecular feature. These findings identify intrinsic differences between CNs and sMNs in FUS-ALS and suggest PLK1 as a potential driver of sMN vulnerability.}, } @article {pmid40857025, year = {2025}, author = {Ercan, V and Kuas, C and Cetin, M}, title = {Commentary on Sheppard et al.'s Study of First Trimester POCUS Behaviors.}, journal = {Academic emergency medicine : official journal of the Society for Academic Emergency Medicine}, volume = {}, number = {}, pages = {}, doi = {10.1111/acem.70130}, pmid = {40857025}, issn = {1553-2712}, } @article {pmid40857020, year = {2025}, author = {Krivickas, B and Scirocco, E and Giacomelli, E and Sharma, S and Benson, M and Keegan, M and Kulesa-Kelley, J and Chibnik, LB and Casagrande, G and Heyd, L and Chase, M and Drake, K and Mohapatra, S and Hagar, JL and Hasenoehrl, MG and Dagostino, D and Sherman, AV and Leite, A and Yu, H and Rosenthal, J and Miller, T and McCaffrey, A and Gwathmey, K and Locatelli, E and Bayat, E and Heitzman, D and Young, E and Goyal, NA and Whitesell, J and Felice, K and Ilieva, H and Swenson, A and Walk, D and Alameda, G and Foster, L and McIlduff, CE and Walsh, A and Zilliox, L and Ajroud-Driss, S and Bodkin, C and Katz, J and Ladha, S and Rivner, M and Rosow, L and Twydell, P and Wasiewski, W and Babu, S and Berry, JD and Paganoni, S}, title = {Multicenter Expanded Access Protocol for Research Through Access to Trehalose in People With Amyotrophic Lateral Sclerosis.}, journal = {Muscle & nerve}, volume = {}, number = {}, pages = {}, doi = {10.1002/mus.70011}, pmid = {40857020}, issn = {1097-4598}, support = {UF1NS131791//Office of the Director of the National Institutes of Health/ ; }, abstract = {INTRODUCTION/AIMS: Expanded access protocols (EAPs) allow individuals ineligible for clinical trials to receive investigational products. EAP data can be collected in parallel to randomized clinical trials (RCTs) and serve as a source of evidence in clinical practice. Here, we present the results of a National Institutes of Health (NIH)-funded EAP for amyotrophic lateral sclerosis (ALS).

METHODS: Participants received trehalose, a drug studied in a parallel RCT, for up to 24 weeks; clinical and biomarker data were collected throughout the study.

RESULTS: Seventy participants were enrolled at 20 study centers across the United States. Treatment with trehalose did not affect the levels of neurofilament light chain [estimated flat slope per month was -0.005, SE = 0.0078; 95% CI (-0.021, 0.011)] or disease progression [estimated least square mean change of the ALS Functional Rating Scale-Revised total score and slow vital capacity (percent predicted) from baseline to Week 24 were -5.6 (0.67); 95% CI (-7.0, -4.3) and -4.53 (4.308); 95% CI (-13.55, 4.48)], respectively. No unexpected treatment-related risks were identified. Serious adverse events were deemed not related to trehalose (20 occurrences in 13 [18.6%] participants with eight deaths).

DISCUSSION: This EAP establishes a framework for implementing multi-center EAPs that complement data collected from RCTs. Additional NIH-funded EAPs are currently underway. Data and additional serum samples collected in this study are available to the research community for further study.

TRIAL REGISTRATION: ClinicalTrials.gov: NCT05597436.}, } @article {pmid40856961, year = {2025}, author = {Solh Dost, L and Guignard, B and Gastaldi, G and Hasan Hamzo, A and Nendaz, M and Audétat, MC and Schneider, MP}, title = {Community pharmacists' practices and clinical reasoning towards hospital discharge prescription: a study using simulations and retrospective think-aloud methodology.}, journal = {International journal of clinical pharmacy}, volume = {}, number = {}, pages = {}, doi = {10.1007/s11096-025-01978-0}, pmid = {40856961}, issn = {2210-7711}, abstract = {BACKGROUND: The roles of community pharmacists have evolved from dispensing medications to clinical decision makers. This shift requires a clearer understanding of pharmacists' clinical reasoning. Managing hospital discharge prescriptions requires analytical reasoning to ensure patient safety through medication reconciliation and patient education.

AIM: This study assessed community pharmacists' practices and their clinical reasoning towards hospital discharge prescriptions.

METHOD: This mixed-method study consisted of two phases. First, community pharmacists participated in a simulated encounter in their pharmacy, where a patient presented a discharge prescription. Their practices and the structure of the encounter were assessed using a structured checklist of practices adapted from the MEDICODE checklist. Following the simulation, participants verbalised their thought processes in a retrospective think-aloud session. These semi-structured interviews were transcribed and analysed using both inductive and deductive qualitative methods. Charlin et al.'s model was used to assess clinical reasoning, while the Calgary-Cambridge model evaluated communication structure.

RESULTS: Among 14 participating pharmacists, 13 performed medication reconciliation, and 10 contacted the simulated prescriber to address discrepancies. While most provided adherence aids, only seven assessed non-adherence, and five actively collaborated with the patient. Pharmacists exhibited diverse interview structures, often revisiting previous discussion points. Clinical reasoning misconceptions, such as assumptions or premature closure, were observed at multiple stages of the clinical reasoning process.

CONCLUSION: Community pharmacists demonstrate strong medication-related skills but face challenges in clinical reasoning for discharge prescriptions. Clinical reasoning training, semi-structured consultations, and greater patient engagement would help tailor and improve post-discharge care.}, } @article {pmid40856865, year = {2025}, author = {Shandilya, C and Mani, S}, title = {Rho kinase isoforms in neurodegeneration: from cellular functions to therapeutic targets.}, journal = {Molecular biology reports}, volume = {52}, number = {1}, pages = {846}, pmid = {40856865}, issn = {1573-4978}, mesh = {Humans ; *rho-Associated Kinases/metabolism/antagonists & inhibitors/genetics ; *Neurodegenerative Diseases/metabolism/drug therapy ; Mitochondria/metabolism ; Animals ; Mitophagy ; Neurons/metabolism ; Protein Isoforms/metabolism ; Signal Transduction ; Reactive Oxygen Species/metabolism ; Mitochondrial Dynamics ; Isoenzymes/metabolism ; Oxidative Stress ; }, abstract = {Mitochondria serve as an important cellular organelle for maintaining neurotransmission and synaptic plasticity in neuronal cells by playing a key role in ATP generation, maintaining calcium homeostasis, and regulating the levels of reactive oxygen species (ROS), etc. The regulation of the dynamic nature of mitochondria, including their fission, fusion, and removal of damaged mitochondria by mitophagy, is also very important for neuronal health. Abnormalities in mitochondrial processes, including but not limited to fission, fusion, and mitophagy, are known to be associated with numerous neurodegenerative diseases (NDDs), such as Parkinson's disease (PD), Alzheimer's disease (AD), Amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD). In the recent past, the Rho kinase (ROCK) isoforms, particularly ROCK1 and ROCK2, have gained a lot of attention in NDDs, mainly for their role in regulating the dynamics of the mitochondria, mitophagy, and other cell signalling pathways. By adding phosphate groups to Drp1, ROCK1 is crucial in supporting excessive mitochondrial fission, causing the death of neuronal cells. On the other hand, ROCK2 inhibits Parkin-dependent mitophagy by inhibiting the PTEN protein, the activator of Parkin-dependent mitophagy. This impaired mitochondrial quality control via reduced mitophagic flux leads to oxidative stress and neuronal degeneration, the central pathological feature of NDDs. The inhibition of ROCK isoforms has shown great promise in neuroprotective effects, controlling the dynamics of mitochondria in neuronal cells, lowering inflammation, and improving motor and cognitive functions in preclinical models of different NDDs, indicating ROCK isoforms as an attractive therapeutic target in different NDDs. This review aims to highlight the therapeutic significance of targeting ROCK isoforms in different NDDs.}, } @article {pmid40856243, year = {2025}, author = {Seven, YB and Seven, ES and Kirbas Cilingir, E and Parikh, K and Aydin, M and Luca, EK and Nair, J and Leblanc, RM}, title = {Rapid mapping of spinal and supraspinal connectome via self-targeting glucose-based carbon dots.}, journal = {Nanoscale}, volume = {}, number = {}, pages = {}, doi = {10.1039/d5nr02670a}, pmid = {40856243}, issn = {2040-3372}, abstract = {The spinal cord is a highly dynamic network, playing significant roles in the vital functions of the brain. Disorders of the spinal cord, such as spinal cord injury and amyotrophic lateral sclerosis (ALS), are associated with neurodegeneration, often resulting in morbidity and mortality. The blood-brain barrier (BBB) poses a major challenge to imaging and therapeutic agents because less than 2% of small-molecule drugs and almost no large-molecule drugs can cross the BBB. Furthermore, spatial spectroscopy studies have shown highly heterogeneous BBB crossing with significant accumulation at the unintended brain regions. Thus, targeting systems that can cross the BBB at the spinal cord and precisely target specific cell types/populations are vitally needed. Carbon dots can be custom-designed to accumulate at the spinal cord; thus, they offer great potential as delivery platforms for imaging and therapeutic approaches. Since neurons are metabolically highly active and rely on glucose, we designed glucose-based carbon dots (GluCDs) with a diameter of ∼4 nm and glucose-like surface groups. We determined the CNS distribution of GluCDs on three scales: 1. brain regional distribution, 2. cellular tropism (e.g. neurons vs. glia), and 3. intracellular localization. We found that GluCDs (1) crossed the BBB at the spinal cord level, localized primarily to the spinal cord, and were quickly transported to higher centers in the brain, revealing supraspinal connectome within 4 hours after systemic delivery (minimally invasive and significantly faster than the available technologies); (2) almost exclusively localized to neurons without the need for a targeting ligand (neuronal self-targeting), and (3) were confined to late endosomal/lysosomal compartments in the neurons. Then, we verified our findings in a cervical spinal cord contusion injury model with GluCDs targeting the neurons at the injury epicenter. Therefore, GluCDs can be used as robust imaging agents to obtain rapid snapshots of the spinal/supraspinal network. GluCD nanoconjugates can open new avenues for targeted imaging of spinal cord injury. These findings can be extended to other spinal disorders such as ALS, spinal muscular atrophy, and spinal stroke.}, } @article {pmid40856102, year = {2025}, author = {Göksun, T and Aktan-Erciyes, A}, title = {Diversity as a Core Feature of Language Acquisition: A Commentary on Scaff et al. (2025).}, journal = {Developmental science}, volume = {28}, number = {5}, pages = {e70064}, doi = {10.1111/desc.70064}, pmid = {40856102}, issn = {1467-7687}, support = {//James S. McDonnell Foundation Human Cognition Scholar Award/ ; }, abstract = {This commentary builds on Scaff et al.'s (2025) systematic review of the CHILDES database, highlighting persistent biases in child language corpora and research. We expand the discussion, emphasizing three key areas: (1) the need to diversify naturalistic data across languages to strengthen language acquisition theories; (2) the importance of including diverse child and parent demographics within specific language environments; and (3) the underrepresentation of bilingual samples from non-WEIRD, non-Indo-European contexts. We argue that these limitations not only hinder generalizability but also shape prevalent theoretical assumptions. Promoting inclusive, globally representative corpora is important for advancing a fair and accurate understanding of child language acquisition. SUMMARY: Diversification of naturalistic data across languages strengthens language acquisition theories. Child and parent characteristics within specific language environments should be included in child language research. Bilingual samples in CHILDES corpora should be evaluated on their generalizability.}, } @article {pmid40856010, year = {2025}, author = {Boyanova, S and Banks, G and Lipina, TV and Bains, RS and Forrest, H and Stewart, M and Carcolé, M and Milioto, C and Isaacs, AM and Wells, SE and Wiseman, FK}, title = {Multi-modal comparative phenotyping of knock-in mouse models of frontotemporal dementia/amyotrophic lateral sclerosis.}, journal = {Disease models & mechanisms}, volume = {18}, number = {8}, pages = {}, doi = {10.1242/dmm.052324}, pmid = {40856010}, issn = {1754-8411}, support = {UKDRI-1014//UK Dementia Research Institute/ ; UKDRI-CIP0202//UK Dementia Research Institute/ ; UKDRI-1203//UK Dementia Research Institute/ ; ARUK-SRF2018A-001//Alzheimer's Research UK/ ; Isaacs/Apr20/876-791/MNDA_/Motor Neurone Disease Association/United Kingdom ; A410-53658/MRC_/Medical Research Council/United Kingdom ; }, abstract = {Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are progressive adult-onset neurodegenerative diseases with overlapping pathological and genetic origins. They are caused by multiple underlying mechanisms leading to a common collection of clinical features that occur in a spectrum. Here, we report side-by-side longitudinal behavioural, cognitive and sensory phenotyping of two mouse models of ALS/FTD, to determine which aspects of the disease they recapitulate. We used knock-in models, in which the endogenous mouse orthologues of the C9orf72 and TARDBP (encoding TDP-43) genes have been altered to model specific molecular aspects of ALS/FTD. We found that the C9orf72GR400/+ model exhibits age-related deficit in short-term memory and that parental genotype affects exploration activity in offspring. In the TardbpQ331K/Q331K model, we found age-related changes in weight, fat mass, locomotion and marble burying. In both models, we found no evidence of deficits in vision or olfactory habituation-dishabituation. These data provide new insight into genotype-phenotype relationships in these ALS/FTD mice, which can be used to inform model choice and experimental design in future research studies.}, } @article {pmid40855953, year = {2025}, author = {Logroscino, G and Giannoni-Luza, S and Urso, D and Hamdi, N}, title = {Heterogeneity of frequencies of motor neuron disease across ethnicities and geographical areas: focus on Arabic countries in the Mediterranean area.}, journal = {Current opinion in neurology}, volume = {}, number = {}, pages = {}, doi = {10.1097/WCO.0000000000001415}, pmid = {40855953}, issn = {1473-6551}, abstract = {PURPOSE OF REVIEW: Although amyotrophic lateral sclerosis (ALS) epidemiology has been increasingly characterized in many regions, data from Arabic countries remain limited. This review aims to summarize the current knowledge on the burden of ALS in Arabic Mediterranean countries, with a particular focus on Egypt.

RECENT FINDINGS: ALS exhibits significant geographic and ethnic variability in terms of incidence, phenotype, and genetic background. Data from the Global Burden of Disease Study 2021 show that Egypt has one of the lowest age-standardized rates of ALS incidence, prevalence, and mortality in the Mediterranean basin. During the past three decades, Egypt has seen a notable decline in ALS-related Disability-Adjusted Life Years and deaths, in contrast to neighboring countries. A national registry has recently been initiated to enhance epidemiological surveillance in the country.

SUMMARY: ALS in Arabic Mediterranean countries presents a distinct epidemiological profile. These differences likely reflect a combination of genetic, demographic, and healthcare-related factors. Strengthening national registries and promoting regional collaborations will be crucial for gaining a deeper understanding of the determinants of ALS in these underrepresented populations.}, } @article {pmid40855203, year = {2025}, author = {Ferreira, J}, title = {Lymphatic system role in ALS.}, journal = {Lab animal}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41684-025-01610-8}, pmid = {40855203}, issn = {1548-4475}, } @article {pmid40854500, year = {2025}, author = {Sheu, KL and Chen, CC and Chen, SC}, title = {Comments on Fakult et al.'s "Epidemiology of Merkel Cell Carcinoma in the United States".}, journal = {Journal of the American Academy of Dermatology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jaad.2025.06.080}, pmid = {40854500}, issn = {1097-6787}, } @article {pmid40854024, year = {2025}, author = {Stiles, K and LaBarbera, V}, title = {Recognition and Treatment of Concurrent Amyotrophic Lateral Sclerosis and Myasthenia Gravis.}, journal = {Rhode Island medical journal (2013)}, volume = {108}, number = {9}, pages = {16-18}, pmid = {40854024}, issn = {2327-2228}, } @article {pmid40853517, year = {2025}, author = {Kokotis, P and Bakola, E and Schmelz, M and Rentzos, M and Papagiannopoupou, G and Tsivgoulis, G}, title = {Motor neuron axonal excitability changes in the clinical course of amyotrophic lateral sclerosis.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {}, number = {}, pages = {}, pmid = {40853517}, issn = {1590-3478}, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal disease characterized by slowly progressive degeneration of upper motor neurons (UMNs) and lower motor neurons (LMNs). Although the pathogenesis of sporadic form of ALS has not been fully elucidated, the initial damage mostly leads to hyperexcitability of the central and peripheral motor neuron. The results of our study aimed to confirm the changes in the excitability of the peripheral motor axon and contribute to the emergence of these measurements as potential biomarkers for disease progression. A total of 56 ALS patients [24 women (43%), median age 62.5 (interquartile range: 53.75-70.25) years] were finally included in the study. Twenty-four healthy controls that were age- and sex-matched to the cases [12 women (50%), mean age 58.46 ± 8.84] were recruited. The first main finding of our study is the fact that abnormalities of the voltage gated K[+] ion channels were constantly present in ALS patients than in the controls. The multivariate analysis revealed that Superexcitability 7ms lower than - 21.06%, related to shorter survival. Additionally using receiver operating characteristic (ROC) curves, the c-statistic showed Superexcitability 7ms moderate predictive ability. The clinical significance of our results is that Superexcitability 7ms can be used as a biomarker not only for survival but also for disease progression.}, } @article {pmid40852304, year = {2025}, author = {Yang, JE and Lee, JH and Boya, BR and Kim, YG and Byun, Y and Lee, J}, title = {Novel Pyrone-Based Biofilm Inhibitors against Azole-Resistant.}, journal = {ACS omega}, volume = {10}, number = {32}, pages = {36441-36454}, pmid = {40852304}, issn = {2470-1343}, abstract = {is an opportunistic fungus that is pathogenic in immunocompromised patients with life-threatening diseases such as HIV and cancer. is the most common fungal species isolated from biofilms formed on implanted medical devices or on human tissue. Biofilm development of is mainly driven by a transition from yeast to hyphal form involving core proteins such as HWP and ALS. We designed and synthesized novel α-pyrone-based analogues to investigate their potential in inhibiting biofilm formation and hyphal development of . Among the synthesized compounds, three compounds (6f, 6j, and 6n) significantly inhibited biofilm formation and reduced cell aggregation and hyphal formation in a dose-dependent manner. These compounds had minimal effects on planktonic cell growth while significantly reducing biofilm formation at 20-50 μg/mL, suggesting novel candidate compounds for managing drug-resistant strains of . The three compounds may represent promising therapeutic options with potential synergistic effects when combined with existing antifungal agents.}, } @article {pmid40852180, year = {2025}, author = {Corcia, P and Stenson, K and Doutriaux, A and Hadjrabia, H and Boer, F and Issa, S and Marguet, S and Bernard, F and Nasanbat, E and Nowacki, G and de Pouvourville, G and Couratier, P}, title = {Epidemiology, disease evolution and economic burden of amyotrophic lateral sclerosis in France using the French national health data system.}, journal = {Brain communications}, volume = {7}, number = {4}, pages = {fcaf292}, pmid = {40852180}, issn = {2632-1297}, abstract = {Amyotrophic lateral sclerosis is a rare neurodegenerative disease that requires multidisciplinary care, resulting in extensive healthcare resource utilization. No study has explored the prevalence of amyotrophic lateral sclerosis or characterized associated healthcare resource utilization in France, despite its high burden on people living with amyotrophic lateral sclerosis, caregivers and the healthcare system. Herein, we conducted a France-wide retrospective study to describe the epidemiology, disease course and economic burden of amyotrophic lateral sclerosis. People living with amyotrophic lateral sclerosis were identified from the French population from 2012 to 2019 using the French national health data system. A milestone and symptom-based staging algorithm was developed to categorize the incident cohort into early, mid and late stages. Data were extracted on epidemiology, demographic and clinical characteristics and clinical treatments. Healthcare resource utilization and costs were analysed for amyotrophic lateral sclerosis cases and matched non-amyotrophic lateral sclerosis controls and at disease stages. Events of interests were identified, and a competing risk analysis was conducted. Comparative statistics were performed using paired t-test, ANOVA and χ[2] test. We identified 18 289 incident amyotrophic lateral sclerosis cases, 56.1% of whom were male. The average age at diagnosis was 68.4 (± 12.5) years. In 2019, the estimated incidence and prevalence were 3.5/100 000 person-years and 11.0/100 000 persons, respectively. All-cause hospitalizations were higher among people at mid stage (1.66 person-years) and late stage (2.82 person-years) than among people at early stage (1.46 person-years) and for the amyotrophic lateral sclerosis cases (1.98 person-years) than for the matched non-amyotrophic lateral sclerosis controls (0.45 person-years). Home hospitalization and rehabilitation admission were more prevalent among people in later stages. The rate of out-patient and ambulatory consultations to all specialties was 13.8 person-years for people at early and mid stages and 11.1 person-years for people at late stage and 13.0 and 8.7 person-years for the amyotrophic lateral sclerosis cases and the matched non-amyotrophic lateral sclerosis controls, respectively. Direct costs increased as the disease progressed and were also higher for the amyotrophic lateral sclerosis cases than for the matched non-amyotrophic lateral sclerosis controls. Amyotrophic lateral sclerosis imposes a significant health burden through incremental healthcare resource utilization across all stages that increases with disease progression. Out-patient and ambulatory resource consumption decreased as the disease progressed to a more severe form, accompanied by a corresponding increase in in-patient services. These findings shed light on the complex needs of people living with amyotrophic lateral sclerosis and the continued need for more efficacious treatments.}, } @article {pmid40851522, year = {2025}, author = {Morgan, KH and Havranek, K and Horn, C and Lee, ML and Thomas, S}, title = {You look at life through a different lens: a phenomenological study of living with amyotrophic lateral sclerosis.}, journal = {Neurodegenerative disease management}, volume = {}, number = {}, pages = {1-11}, doi = {10.1080/17582024.2025.2546761}, pmid = {40851522}, issn = {1758-2032}, abstract = {AIMS: Amyotrophic lateral sclerosis (ALS) is a motor neuron disease that progresses without periods of remission; few live more than five years beyond diagnosis. In this study we investigated the lived experiences of people diagnosed with ALS in the United States, in South Central Appalachia.

PATIENTS & METHODS: We selected the philosophical and methodological approach of existential phenomenology of Merleau-Ponty to identify what was most important or figural to participants, within the contexts of Body, Other People, World, and Time.

RESULTS: Through phenomenological interviews with 10 people living with ALS, six themes and 17 subthemes were identified covering the process of diagnosis, loss and devastation, support from others, assistive devices, a new purpose, and a change in perspective.

CONCLUSIONS: These themes offer insight into life with an ALS diagnosis so that this unique patient population may be better understood from a physical, medical, emotional, and spiritual standpoint.}, } @article {pmid40851455, year = {2025}, author = {Ido, BJF and Dabilgou, AA and Doulgou, AS and Carama, EA and Ganame, MKL and Napon, C}, title = {Epidemiology, clinical features, and management of amyotrophic lateral sclerosis in the neurology department of the Bogodogo University Hospital in Ouagadougou, Burkina Faso.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {}, number = {}, pages = {1-3}, doi = {10.1080/21678421.2025.2549323}, pmid = {40851455}, issn = {2167-9223}, abstract = {Objective: To describe the epidemiology, the clinical features, and the management of amyotrophic lateral sclerosis (ALS) in the neurology department of the Bogodogo University Hospital. Methods: This was a retrospective study including patients followed in the neurology department of the Bogodogo University Hospital between April 15, 2017 and December 31, 2024 for ALS. The socio-demographic, clinical and follow-up data of these patients were studied. Results: During our study period, 14 patients were followed for ALS, an average of 2 cases per year. The mean age of patients at symptom onset was 38.50 ± 14.23 years. The mean time to diagnosis was 19.71 ± 5.27 months. Four patients underwent no spinal cord magnetic resonance imaging (MRI). Riluzole was prescribed in 02 patients (14.29%). No patient benefited from noninvasive ventilation or gastrostomy. Six patients (42.85%) were discharged against medical advice. On December 31, 2024, there were 2 patients alive (14.29%), 5 patients who died (14.29%) and 7 patients (50%) who were lost to follow-up. Conclusion: Our cohort is characterized by a low hospital incidence, a young age of patients and difficulties in the care and follow-up of patients.}, } @article {pmid40851280, year = {2025}, author = {Tröger, J and Rouvalis, A and Dörr, F and Schwed, L and Linz, N and König, A and Machts, J and Vielhaber, S and Thies, T and Prudlo, J and Hermann, A and Kasper, E}, title = {Automatically measured speech intelligibility models bulbar-specific disease severity and progression in Amyotrophic Lateral Sclerosis.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {}, number = {}, pages = {1-9}, doi = {10.1080/21678421.2025.2549317}, pmid = {40851280}, issn = {2167-9223}, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that leads to widespread motor deterioration, including significant motor speech impairments. Speech intelligibility is a crucial component of communication affected in ALS, requiring objective, scalable assessment methods as an indicator of disease progression and treatment efficacy. Objective: This study investigates whether speech and bulbar function in ALS could be evaluated and monitored utilizing an automated digital measure of speech intelligibility derived from naturalistic picture descriptions. Methods: Speech recordings from 44 patients living with ALS (plwALS) and 49 matched healthy controls (HC) were analyzed and processed utilizing an automated speech analysis pipeline to extract an intelligibility score. These were part of a cross-sectional and longitudinal study involving two assessments. Results: The findings confirmed that speech intelligibility is significantly reduced in plwALS compared to HC. Those with bulbar-onset ALS have lower intelligibility than those with spinal-onset ALS, and the intelligibility of individuals with bulbar symptoms-regardless of the onset type-is lower than in plwALS without bulbar symptoms. Declining ALS-related speech scores correspond with worsening intelligibility in longitudinal assessments. Intelligibility correlates strongly with bulbar-specific clinical measures but not with global scores, highlighting its role in tracking bulbar progression. In some plwALS, we were able to demonstrate that automated speech analyses are more effective in detecting worsening in intelligibility earlier than standard clinical scoring. Conclusion: Our findings highlight that automated speech intelligibility assessments can be a valuable marker to improve clinical monitoring and facilitate earlier intervention in ALS as a supplement to standard assessments.}, } @article {pmid40849781, year = {2025}, author = {Kurochkina, N and Rudrabhatla, P}, title = {Role of Calmodulin in Neurodegeneration and Neuroprotection.}, journal = {Mini reviews in medicinal chemistry}, volume = {}, number = {}, pages = {}, doi = {10.2174/0113895575403663250812115441}, pmid = {40849781}, issn = {1875-5607}, abstract = {Intracellular calcium (Ca2+) levels are critical in maintaining cellular activities and are tightly regulated. Neuronal degeneration and regeneration rely on calcium-binding proteins. Calmodulin (CaM) is a calcium sensor and the primary regulator of receptors and ion channels that maintain calcium homeostasis. The calmodulin binding domains are present in proteins that serve as risk factors and biomarkers associated with Alzheimer's disease, Parkinson's disease, Huntington's disease, Amyotrophic Lateral Sclerosis, and other neurodegenerative diseases, suggesting calmodulin ligands as emerging therapeutic targets for treatment. Inhibiting CaM to develop new therapies has drawbacks, as CaM is a ubiquitous molecule involved in many regulatory pathways. Recently, new strategies for disrupting CaM interactions with its targets have shown promising approaches to treatment. The structures of human CaM, its binding proteins, and inhibitors are well studied, with particular emphasis on the conservation of CaM amino acid sequences and the ability to bind protein fragments of high sequence variability, which exhibit common characteristics of amphipathic helices carrying basic amino acids. In this review, we discuss structural characteristics of CaM and its ligands in the context of transcriptional regulation. Specific binding of CaM to (1) basic region/helix-loop-helix/leucine zipper and (2) helix-turn-helix high mobility group box containing Sox families of transcription factors highlights common features of CaM binding sequences, which suggest their regulatory functions. We describe key proteins involved in neurodegeneration and transcription factors subject to calmodulin regulation that are candidates for the development of new approaches to treating neuronal diseases.}, } @article {pmid40849485, year = {2025}, author = {Helal, MM and AbouShawareb, H and Abbas, OH and Haddad, R and Zain, Y and Osman, ASA and Hassan, AK}, title = {GLP-1 receptor agonists in Parkinson's disease: an updated comprehensive systematic review with meta-analysis.}, journal = {Diabetology & metabolic syndrome}, volume = {17}, number = {1}, pages = {352}, pmid = {40849485}, issn = {1758-5996}, abstract = {Previous studies have demonstrated an increased risk of developing Parkinson's disease (PD) in patients with type 2 diabetes mellitus (T2DM), as well as more severe and rapid motor and non-motor deterioration in diabetic PD patients compared to their non-diabetic counterparts. Additional research has suggested that diabetic subjects treated with glucagon-like peptide-1 (GLP-1) receptor agonists exhibit a reduced incidence of PD compared to those receiving other anti-diabetic medications. GLP-1 receptor agonists are FDA-approved therapies for T2DM, and recent studies have explored their potential as repurposed treatments for neurodegenerative diseases, including PD, AD, and ALS, as well as cerebrovascular disorders. This systematic review aims to assess the available literature on the efficacy and safety profiles of GLP-1 receptor agonists in PD management. A comprehensive search of PubMed, Scopus, CENTRAL, Web of Science, Embase, and ClinicalTrials.gov was conducted to identify relevant studies. The primary outcomes of this review include motor impairment in PD, as assessed by MDS-UPDRS Part III, as well as motor complications (Part IV) and motor experiences of daily living (Part II), and the incidence of gastrointestinal and systemic side effects. Meta-analysis showed that GLP-1 receptor agonists significantly improved motor function, as reflected by MDS-UPDRS Part III scores in the ON state (mean difference = - 2.88; p = 0.01; I[2] = 30%), although they were associated with a higher incidence of adverse events across all safety outcomes. Findings and conclusions of this review will contribute to a clearer understanding of the therapeutic potential of GLP-1 receptor agonists in PD, guiding future clinical research and treatment strategies.}, } @article {pmid40849231, year = {2025}, author = {Fu, X and Gable, K and Gupta, SD and Zhang, K and Jia, B and Wang, W and Yang, X and Wang, L and Ge, L and Bönnemann, CG and Dunn, TM and Xiong, H}, title = {Characterization of novel and recurrent SPTLC2 variants in childhood-onset amyotrophic lateral sclerosis: Insights into sphingolipid dysregulation.}, journal = {Journal of neuromuscular diseases}, volume = {}, number = {}, pages = {22143602251370586}, doi = {10.1177/22143602251370586}, pmid = {40849231}, issn = {2214-3602}, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a severe neurodegenerative disorder that progressively affects motor neurons. Gain-of-function mutations in serine palmitoyltransferase (SPT) genes, notably SPTLC1 and SPTLC2, have been linked to juvenile ALS. Here, we describe two childhood-onset ALS cases with distinct SPTLC2 mutations, providing new insights into sphingolipid dysregulation and its role in ALS pathogenesis.

MATERIAL AND METHODS: Two Chinese patients with early-onset ALS, both carrying SPTLC2 mutations, were recruited from Beijing Children's Hospital. We conducted whole-exome sequencing (WES) to identify genetic variants, followed by Sanger sequencing for validation. Sphingolipid profiles were analyzed using ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Clinical evaluations included neurological assessments, brain MRI and electromyography. Additionally, mutant cell lines were established to assess the functional effects of the specific mutations.

RESULTS: Patient 1, a 6-year-old male, exhibited a novel heterozygous de-novo SPTLC2 variant (c.197T > G, p.T66R). Patient 2, a 7-year-old female, had a recurrent heterozygous de-novo SPTLC2 variant (c.778G > A, p.E260K). Both patients showed elevated levels of specific sphingolipids compared to controls, with distinct profiles between the SPTLC2-ALS and SPTLC1-hereditary sensory and autonomic neuropathy type 1 (HSAN1) cases. The novel p.T66R mutation was predicted to alter protein interactions within the SPT complex, potentially impairing sphingolipid homeostasis. Functional studies further revealed that the p.T66R variant reduces the inhibitory regulation of SPT by ORMDL proteins, leading to unrestrained SPT activity and excess sphingolipid production.

CONCLUSIONS: Our findings identify a novel SPTLC2 variant linked to childhood-onset ALS and reveal altered sphingolipid profiles associated with different genetic mutations. These results underscore the importance of sphingolipid metabolism in ALS and suggest potential avenues for targeted therapeutic interventions. Further research is needed to explore treatment options aimed at modulating sphingolipid levels and correcting genetic defects, as well as investigating potential biomarkers for early diagnosis.}, } @article {pmid40848858, year = {2025}, author = {Chen, X and Ma, Y and Liu, H and Wang, Y}, title = {Multifunctional regulation and treatment of ubiquitin specific protease 10.}, journal = {Biochemical pharmacology}, volume = {}, number = {}, pages = {117251}, doi = {10.1016/j.bcp.2025.117251}, pmid = {40848858}, issn = {1873-2968}, abstract = {USP10 is a critical deubiquitinating enzyme within the ubiquitin-specific protease family, playing multifaceted roles in cellular physiology and disease pathogenesis. Structurally composed of a G3BP1-interacting motif, a N-terminal domain (mediating most protein interactions), and a catalytic USP domain (residues 415-795, catalytic triad C424-H736-D751), USP10 regulates diverse cellular pathways by stabilizing key proteins through deubiquitination. It exhibits context-dependent functional duality, particularly in cancer: USP10 promotes tumorigenesis in various cancers (e.g., glioblastoma, esophageal, pancreatic, breast cancers) by stabilizing oncoproteins like CCND1, YAP1, HDAC7, and RUNX1, enhancing proliferation, metastasis, and immune evasion. Conversely, it suppresses tumors (e.g., NSCLC, CRC, thyroid cancer) by stabilizing tumor suppressors like p53, PTEN, and Axin1, inhibiting pathways such as Wnt/β-catenin. Beyond oncology, USP10 contributes to neurodegenerative diseases (neuroprotective in PD/ALS, neurotoxic in AD via Tau stabilization), viral immunity (inhibits SARS-CoV-2 infection), inflammatory responses, male reproduction, and metabolic/cardiovascular disorders. Its regulatory mechanisms include phosphorylation (e.g., by AMPK, AKT, ATM) controlling subcellular localization and activity, and ubiquitination via USP13. USP10's therapeutic significance drives inhibitor development (Spautin-1, D1, Wu-5, P22077, Parthenolide), though cross-reactivity within the USP family due to conserved catalytic domains remains a challenge. Novel strategies like PROTACs and engineered ubiquitin variants (UbVs) offer promise for future selective targeting of USP10 dysregulation in diverse diseases. A comprehensive understanding of its structure and context-specific functions is essential for exploiting its full therapeutic potential.}, } @article {pmid40848625, year = {2025}, author = {Gauden, AJ and Gu, B and Han, S and Telischak, NJ and Dodd, R and Do, HM and Marks, MP and Steinberg, GK}, title = {Multimodality treatment maximizing outcome in spinal dural arteriovenous fistulae.}, journal = {Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia}, volume = {141}, number = {}, pages = {111571}, doi = {10.1016/j.jocn.2025.111571}, pmid = {40848625}, issn = {1532-2653}, abstract = {BACKGROUND: Spinal dural arteriovenous fistula (sDAVF) is a rare cause of myelopathy and progressive paraplegia. sDAVFs are the most frequent type of spinal vascular malformation and comprise 70 % of all vascular spinal malformations. Despite the availability and published efficacy of both microsurgical resection and endovascular embolization, the optimal treatment for sDAVFs remains to be determined. We aimed to assess the efficacy of a multimodal treatment approach to sDAVFs at our institution.

METHODS: A retrospective review of all sDAVFs treated between 1998 and 2021 at Stanford Hospital and Clinics was conducted. The medical records were inspected and data, including presenting symptoms, duration, angiographic features, and treatment modality, were extracted. Cure was defined as the absence of an arteriovenous fistulous connection on digital subtraction angiography and radiologic improvement on follow-up MRI. Functional outcomes were assessed at presentation and at last follow-up using the Aminoff-Logue Scale (ALS).

RESULTS: 47 patients underwent treatment of sDAVFs between August 1998 to May 2021. As an initial treatment, 32 patients underwent microsurgical excision, and 15 had endovascular embolization. Radiological cure was achieved in 84.4 % of patients during the first treatment and in 97.9 % of patients at the final treatment time point. At initial treatment, surgery cured the sDAVF in 84.4 % of patients, with endovascular embolization curing in 86.7 % of patients. When assessed as an additional treatment for failed prior treatment, surgery achieved cure in 80 % of patients and endovascular embolization in 100 % of patients. At all time points, high cure rates were observed, with success rates achieving 96.9 % and 100 % for surgery and endovascular embolization, respectively. A significant improvement in ALS Gait score was noted after treatment, with a mean reduction of 0.6 from baseline (p = 0.0003). A similar improvement trend was observed in the ALS Micturition score with a mean decrease of 0.3 points (p = 0.057).

CONCLUSIONS: Our study demonstrates high efficacy for cure and improved functional outcomes in both surgical and endovascular treatments, assuming good patient selection. This series also highlights the importance of a multimodality treatment approach in managing spinal dural arteriovenous fistulae. Further delineation is required to determine the radiological and patient factors that might recommend specific initial treatment modalities.}, } @article {pmid40848497, year = {2025}, author = {Jiang, W and Su, Y and Guo, M and Wang, X and Liu, H and Liu, X and Zhang, Y}, title = {Detection of aging-induced vascular remodeling based on Raman imaging and deep learning.}, journal = {Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy}, volume = {345}, number = {}, pages = {126832}, doi = {10.1016/j.saa.2025.126832}, pmid = {40848497}, issn = {1873-3557}, abstract = {Vascular aging-related remodeling is a common pathological basis for many chronic diseases, so early detection of physical arterial aging is important for their prevention and control. Existing staining methods can only analyze a limited number of tissue components at a time and often suffer from inaccuracies caused by over- or under-staining. In this study, we performed high-quality Raman imaging to simultaneously analyze five components in mouse aortic sections: elastic fibers, types I and III collagen fibers, nuclei, and cytoplasm of vascular smooth muscle cells (VSMCs), detailing their content and distribution changes. Despite subtle differences in Raman spectra, young and aged aortic tissues were successfully distinguished using multivariate curve resolution-alternating least squares (MCR-ALS) analysis and deep learning, achieving an AUC of 0.986 (95 % CI: 0.979-0.992). Additionally, Raman imaging and metabolomics revealed metabolic changes in arterial aging related to collagen synthesis and post-modifications, offering new potential therapeutic targets. Thus we show that Raman imaging combined with advanced algorithms is potentially useful in detecting vascular-aging remodeling, as well as monitoring the aging process.}, } @article {pmid40848171, year = {2025}, author = {Xu, H and Shao, Y and Zhang, J and Ni, Y and Xu, G and Liu, C and Liang, Y and Le, W}, title = {HSF-1 Regulates Autophagy to Govern Motor Function and Facilitate Toxic Protein Clearance in a C. elegans Model of Amyotrophic Lateral Sclerosis.}, journal = {Neuroscience bulletin}, volume = {}, number = {}, pages = {}, pmid = {40848171}, issn = {1995-8218}, abstract = {Heat shock factor-1 (HSF-1) plays a crucial role in orchestrating stress responses across diverse organisms and disease conditions. Here, we investigate how the HSF-1 signaling pathway influences the degradation of toxic proteins and neuropathological changes in the Caenorhabditis elegans model of amyotrophic lateral sclerosis (ALS). We found that overexpressing HSF-1 improves locomotor ability and increases the survival rate of ALS C. elegans. Moreover, we observed a deceleration of motor neuron degeneration, demonstrating the protective effect of HSF-1 on neurodegenerative processes. Transcriptomic analysis revealed notable changes in genes associated with autophagy and neurodegeneration, underscoring HSF-1's critical involvement in ALS pathology. In addition, metabolomic profiling further highlighted the involvement of this pathway in metabolic reprogramming. Overall, our study underscores the critical role of the HSF-1 signaling pathway in improving survival rate, movement velocity, cellular integrity, and metabolic adaptation, providing new insights into the mechanisms underlying ALS and potential targets for therapeutic intervention.}, } @article {pmid40847753, year = {2025}, author = {Yang, M and Wang, Q and Yan, R and Wang, X and Gu, J}, title = {Dimer-Specific FokT-seq Reveals DNA-Binding Dimerization and Novel Genomic Targets of TDP-43.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {}, number = {}, pages = {e08902}, doi = {10.1002/advs.202508902}, pmid = {40847753}, issn = {2198-3844}, support = {32171258//National Natural Science Foundation of China/ ; 82330041//National Natural Science Foundation of China/ ; 92049107//National Natural Science Foundation of China/ ; 2022-72-18//Department of Science and Technology of Hubei Province/ ; }, abstract = {In postmortem brain tissues of patients with sporadic amyotrophic lateral sclerosis (ALS), the dimerization ability of TAR DNA-binding protein 43 (TDP-43) is impaired, accompanied by an accumulation of insoluble TDP-43. Thus, the loss of TDP-43 dimerization may play a critical driving role in ALS pathogenesis, although its underlying mechanism remains unclear. In this study, the FokT (FokI-TDP-43) system is developed, which fuses TDP-43 protein with FokI nuclease. By restoring TDP-43 dimerization, this system reactivates FokI nuclease activity, enabling the cleavage of DNA targets bound by TDP-43. Additionally, the FokT-seq (FokT combined with genome-wide unbiased identification of DNA double-strand breaks enabled by sequencing, Guide-seq) method is established, allowing genome-wide detection of DNA sites bound by dimerized TDP-43. These findings reveal the essential role of TDP-43 dimerization in DNA binding, identify a series of related targets. Furthermore, this study offers a powerful tool for investigating dimerized transcription factors.}, } @article {pmid40847737, year = {2025}, author = {Novikov, V and Timothy, LTC and Fan, J and Sadek, K and Cowan, MF and Onuska, KM and Duennwald, M and Prado, VF and Prado, MAM}, title = {A Longitudinal Study of Sex Differences in a TDP-43 Mouse Model Reveals STI1 Regulation of TDP-43 Proteinopathy and Motor Deficits.}, journal = {Journal of neurochemistry}, volume = {169}, number = {8}, pages = {e70204}, doi = {10.1111/jnc.70204}, pmid = {40847737}, issn = {1471-4159}, support = {03592-2021 RGPIN//Natural Sciences and Engineering Research Council of Canada/ ; 06577-2018 RGPIN//Natural Sciences and Engineering Research Council of Canada/ ; //Canadian Institutes of Health Research CGS-D/ ; //ALS Society of Canada/ ; PJT 159781/CAPMC/CIHR/Canada ; PJT 162431/CAPMC/CIHR/Canada ; //Canadian Institutes of Health Research CGS-M/ ; }, mesh = {Animals ; Mice ; Male ; Female ; *DNA-Binding Proteins/genetics/metabolism ; *Sex Characteristics ; Mice, Transgenic ; *TDP-43 Proteinopathies/metabolism/genetics/pathology ; Disease Models, Animal ; *Amyotrophic Lateral Sclerosis/metabolism/genetics/pathology ; Longitudinal Studies ; Humans ; *HSP90 Heat-Shock Proteins/metabolism/genetics ; Mice, Inbred C57BL ; Spinal Cord/metabolism ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a disease influenced by a complex interplay of age, genetics, and sex. Most ALS cases are sporadic, and individuals with this disease show elevated levels of TDP-43 in their central nervous system and aggregated cytoplasmic inclusions containing TDP-43 in neurons. Misfolded and aggregated proteins like TDP-43 can be refolded or marked for degradation by molecular chaperones and their co-chaperone partners. In this study, we use a mouse model of ALS that mildly overexpresses human wild-type TDP-43 in neurons to explore how aging affects the onset of motor abnormalities and proteinopathy in male and female mice. We found that the age-dependent onset of motor symptoms is more pronounced in male mice, despite both sexes sharing similar TDP-43 pathology. Further, we found that reducing the activity of STI1, an Hsp90 co-chaperone, was associated with reduced mislocalized TDP-43 in the brain and spinal cord and partially rescued some motor deficits. By contrast, overexpressing STI1 seemed to be deleterious, exacerbating the levels of C-terminal TDP-43 fragments in the cytoplasm, worsening motor abnormalities and reducing lifespan. Our findings reveal that sex is a key biological factor in an ALS mouse model of TDP-43 overexpression and provide novel insights on the role of STI1 and proteostasis in mediating TDP-43 pathology.}, } @article {pmid40847590, year = {2025}, author = {Spillinger, A and Ellefson, J and Yang, Q and Yin, LX and Stokken, JK and Pasic, T and Koszewski, IJ and Lin, SY}, title = {External Validation of a Multivariable Diagnostic Prediction Model for Acute Invasive Fungal Rhinosinusitis in Tertiary Care Settings.}, journal = {International forum of allergy & rhinology}, volume = {}, number = {}, pages = {}, doi = {10.1002/alr.70024}, pmid = {40847590}, issn = {2042-6984}, abstract = {BACKGROUND: Prompt detection and intervention are crucial for improving outcomes in acute invasive fungal rhinosinusitis (AIFS). Diagnostic prediction models assist in risk-stratification, but their accuracy requires testing through external validation. This study aims to validate a previously published diagnostic prediction model for AIFS in an independent cohort.

METHODS: A retrospective chart review was conducted at a tertiary care center (2008-2023) to identify patients with an otolaryngology consult for suspected AIFS. Of 65 patients identified, 11 (16.9%) were diagnosed with AIFS based on histopathology. Risk was calculated using Yin et al.'s predictive model. Predictive performance was assessed by calibration and discrimination.

RESULTS: Patients had significantly higher rates of diabetes (46.2% vs. 26.1%, p = 0.002), long-term steroid use (60% vs. 28.2%, p < 0.0001), and solid organ transplantation (38.5% vs. 8.5%, p < 0.001), compared with the development cohort, with conversely lower rates of hematologic malignancy (29.2% vs. 58.7, p < 0.001) and neutropenia (19.4% vs. 41%, p = 0.001). Despite these differences, both the three-variable (C-index: 0.844; 95% CI, 0.736-0.952) and four-variable models (C-index: 0.963; 95% CI, 0.919-1) showed adequate discrimination. Both models exhibited slight overprediction of risk, with a calibration-in-the-large predicted risk of 24.1% (95% CI, 13.68-34.46) for the three-variable model and 24.2% (95% CI, 13.76-34.57) for the four-variable model. Calibration plots confirmed overprediction.

CONCLUSION: The AIFS diagnostic model demonstrates acceptable discrimination and calibration on external validation, with generalizability to patients with different comorbidities. Larger studies are recommended to further test the model's predictive performance and clinical applicability.}, } @article {pmid40846833, year = {2025}, author = {Won, W and Lee, EH and Gotina, L and Chun, H and Lee, JH and Bhalla, M and Park, U and Kim, D and Kim, TY and Choi, JW and Kim, Y and Park, SJ and Lim, J and Park, JH and Kim, HJ and Heo, JY and Chung, W and Oh, MJ and An, HJ and Lee, J and Oh, SJ and Ryu, H and Pae, AN and Park, KD and Lee, CJ}, title = {Hemoglobin as a pseudoperoxidase and drug target for oxidative stress-related diseases.}, journal = {Signal transduction and targeted therapy}, volume = {10}, number = {1}, pages = {270}, pmid = {40846833}, issn = {2059-3635}, support = {IBS-R001-D2//Institute for Basic Science (IBS)/ ; }, mesh = {*Oxidative Stress/drug effects/genetics ; Humans ; Hydrogen Peroxide/metabolism ; Animals ; *Hemoglobins/metabolism/genetics ; *Alzheimer Disease/drug therapy/genetics/pathology/metabolism ; Astrocytes/metabolism/drug effects/pathology ; Mice ; *Parkinson Disease/drug therapy/genetics/pathology/metabolism ; Dopaminergic Neurons/metabolism/pathology/drug effects ; }, abstract = {Hemoglobin (Hb) is well known for transporting oxygen in the blood, but its role in the brain remains poorly understood. Here, we identified Hb in the cytosol, mitochondria, and nuclei of hippocampal and substantia nigra astrocytes and dopaminergic neurons. As a pseudoperoxidase, Hb decomposes hydrogen peroxide (H2O2) and mitigates H2O2-induced oxidative damage. However, in Alzheimer's disease, Parkinson's disease, and aging, excessive H2O2 diminishes astrocytic Hb, perpetuating a vicious cycle of oxidative stress and neurodegeneration. To counter the harmful effects of aberrant H2O2 production in diseases, we developed KDS12025, a BBB-permeable small molecule that enhances Hb pseudoperoxidase activity 100-fold, even at a low level of Hb. KDS12025 and its analogs achieve this enhancement through its electron-donating amine group, possibly stabilizing the complex between Hb, H2O2, and KDS12025. KDS12025 reduces astrocytic H2O2, alleviates astrogliosis, normalizes Hb, and reverts to a virtuous cycle of redox balance, preventing neurodegeneration without altering the oxygen-transport function of Hb. Gene silencing of Hb abrogates the impact of KDS12025 in both culture and animal models, confirming the necessity of Hb for the effects of KDS12025. KDS12025 extends survival and improves motor function even in severe amyotrophic lateral sclerosis and aging. Furthermore, the enrichment of astrocytic Hb in the nucleolus highlights a novel antioxidative mechanism potentially protecting against nuclear oxidative damage. Our findings suggest that Hb is a new therapeutic target for neurodegenerative diseases, with KDS12025 emerging as a first-in-class approach that enhances Hb pseudoperoxidase activity to reduce H2O2. Increasing Hb pseudoperoxidase activity with KDS12025 mitigates oxidative stress and alleviates neurodegeneration in AD, PD, and ALS patients and increases the degree of aging, with broad applicability for numerous oxidative-stress-driven diseases.}, } @article {pmid40846160, year = {2025}, author = {Chen, J and Liu, J}, title = {Navigating the paradoxes and potential of digital phenotyping for bipolar relapse prediction.}, journal = {Journal of affective disorders}, volume = {}, number = {}, pages = {120116}, doi = {10.1016/j.jad.2025.120116}, pmid = {40846160}, issn = {1573-2517}, abstract = {This commentary responds to the important study by Ludwig et al. on using smartphone data and critical slowing down (CSD) to predict bipolar disorder (BD) relapse. While commending the study's methodological rigor, we highlight a key paradoxical finding: a decrease in activity variance preceding manic episodes, which challenges the classic CSD model. We posit this may not be a failure of the theory but instead reveals a distinct pre-manic signature of behavioral 'rigidification' rather than instability. Furthermore, we discuss the ambiguity of the 'euthymic' baseline in a clinically complex, medicated population, suggesting that unmeasured pharmacological effects may confound the detected signals. The commentary argues that the limited individual-level predictive power underscores the need to shift from searching for universal nomothetic signals to developing personalized, idiographic (N-of-1) models. Ultimately, we conclude that Ludwig et al.'s work is pivotal in reframing the research agenda towards more nuanced, individualized, and clinically translatable digital phenotyping for BD.}, } @article {pmid40845103, year = {2025}, author = {Neeves, J and Petrić Howe, M and Ziff, OJ and Callaghan, B and Jutzi, D and Pal, K and Roumeliotis, TI and Choudhary, J and Isaacs, AM and Rigo, F and Bennett, CF and Ruepp, MD and Patani, R}, title = {An alternative cytoplasmic SFPQ isoform with reduced phase separation potential is up-regulated in ALS.}, journal = {Science advances}, volume = {11}, number = {34}, pages = {eadt4814}, doi = {10.1126/sciadv.adt4814}, pmid = {40845103}, issn = {2375-2548}, mesh = {*Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology ; Humans ; *Cytoplasm/metabolism ; Protein Isoforms/genetics/metabolism ; *Alternative Splicing ; *PTB-Associated Splicing Factor/genetics/metabolism ; RNA, Messenger/genetics/metabolism ; Cell Nucleus/metabolism ; *Up-Regulation ; Animals ; Phase Separation ; }, abstract = {Splicing factor proline- and glutamine-rich (SFPQ) is an RNA binding protein that broadly regulates RNA metabolism. Although its nuclear roles are well studied, evidence of SFPQ's cytoplasmic functionality is emerging. Altered expression and nuclear-to-cytoplasmic redistribution of SFPQ have been recognized in amyotrophic lateral sclerosis (ALS) pathology, yet the mechanistic bases for these phenomena remain undetermined. We identified altered SFPQ splicing in ALS, increasing the expression of an alternative mRNA isoform lacking a nuclear localization sequence, which we termed "altSFPQ." We find that altSFPQ mRNA contributes to SFPQ autoregulation and is highly unstable yet exhibits context-specific translation with cytoplasm-predominant localization. Notably, reduced canonical SFPQ coincides with increased altSFPQ transcript expression in familial and sporadic ALS models, providing a mechanistic basis for SFPQ nuclear-to-cytoplasmic redistribution in patients with ALS. Last, we observe that the altSFPQ protein has reduced phase separation potential and differential protein binding compared to its canonical counterpart, providing insight into its mechanistic relevance to physiology and ALS pathogenesis.}, } @article {pmid40844868, year = {2025}, author = {Ramgopal, S and Cash, R and Martin-Gill, C}, title = {Agency-Level Factors Associated with EMS Volume for High-impact Clinical Conditions and Patient Populations.}, journal = {Prehospital emergency care}, volume = {}, number = {}, pages = {1-14}, doi = {10.1080/10903127.2025.2550598}, pmid = {40844868}, issn = {1545-0066}, abstract = {BACKGROUND: Emergency medical services (EMS) agencies play a crucial role in delivering prehospital care, yet significant variability exists in EMS call volume and the conditions encountered. Variation in EMS call volume across agencies (i.e., high- vs. low-frequency) for specific patient populations and clinical presentations across EMS agencies can have substantial impact on implementation strategies for new guidelines and performance measures. We sought to evaluate agency-level factors associated with EMS volume of specific clinical presentations to inform the planning of targeted quality improvement efforts and resource allocation related to specific high-impact clinical categories.

METHODS: We conducted a retrospective analysis of the 2022 and 2023 National EMS Information System datasets, identifying EMS agencies that consistently reported patient encounters over a two-year period. We categorized encounters by key patient populations and clinical presentations, including cardiac arrest, trauma, stroke, pediatric cases, advanced airway management, and non-transport disposition. We used negative binomial regression to assess factors associated with EMS volumes.

RESULTS: We included 7,230 EMS agencies, with 55,705,469 encounters. The median number of encounters by EMS agency was 1,988 encounters averaged per year (IQR 706-5,584 encounters averaged per year). Cardiac arrest was more frequent in mixed/volunteer agencies and less common in for-profit, non-hospital, and tribal-based EMS services. Trauma volume was higher in advanced life support (ALS) and critical care agencies, the West (relative to Midwest), and mixed/volunteer agencies (relative to non-volunteer agencies). Stroke volume was linked to greater ALS/critical care agencies and mixed/volunteer agencies but was lower in urban areas. Pediatric encounters were more common in urban, mixed/volunteer agencies, and tribal services but less frequent in for-profit and hospital-based agencies. Airway interventions were associated with ALS/critical care agencies, but were less frequent in tribal agencies. Non-transport occurred more commonly in ALS agencies and tribal agencies.

CONCLUSIONS: Distinct patterns of agency-level characteristics appear to exist in relation to the volume of EMS responses for specific patient populations and clinical presentations. These findings can inform agency-specific strategic planning for guideline implementation, resource allocation, and quality improvement in prehospital care.}, } @article {pmid40844737, year = {2025}, author = {Manini, A and Brusati, A and Grassano, M and Scacciatella, G and Peverelli, S and Spagliardi, J and Pensato, V and Doretti, A and Vasta, R and Manera, U and Canosa, A and Brunetti, M and Gentilini, D and Messina, S and Verde, F and Moglia, C and Morelli, C and Dalla Bella, E and Keagle, PJ and Landers, JE and Gellera, C and Lauria Pinter, G and Chiò, A and Ratti, A and Calvo, A and Silani, V and Ticozzi, N}, title = {Whole genome sequencing analysis in primary lateral sclerosis (PLS) patients reveals mutations in neurological diseases-causing genes.}, journal = {Journal of neurology}, volume = {272}, number = {9}, pages = {587}, pmid = {40844737}, issn = {1432-1459}, support = {RF-2021-12374238//Ministero della Salute/ ; RF-2018-12367768//Ministero della Salute/ ; }, mesh = {Humans ; Male ; Female ; Middle Aged ; Aged ; *Motor Neuron Disease/genetics ; Adult ; *Mutation/genetics ; Whole Genome Sequencing ; }, abstract = {BACKGROUND: Primary Lateral Sclerosis (PLS) is a rare, adult-onset neurodegenerative disease that predominantly affects upper motor neurons. Despite being considered mostly sporadic, familial cases and rare genetic variants in genes associated with amyotrophic lateral sclerosis, hereditary spastic paraplegia and other neurological disorders have been reported in some PLS cases. Due to its rare prevalence among general population, large genetic studies of PLS are lacking.

METHODS: Fifty patients diagnosed with PLS based on consensus criteria were enrolled between 2013 and 2022 for comprehensive phenotypic and genotypic analysis using whole genome sequencing. We analyzed rare single nucleotide variants (SNVs), deemed pathogenic, likely pathogenic or of uncertain significance (VUS) based on the American College of Medical Genetics and Genomics criteria, and repeat expansions (REs) exceeding the pathogenic threshold, in 290 genes involved in neurological disorders.

RESULTS: We identified mutations in 7 patients (13.7%), specifically SNVs in CAPN1 (Spastic paraplegia 76), TBK1 (amyotrophic lateral sclerosis/frontotemporal dementia, ALS4/FTD), LITAF (Charcot-Marie-Tooth disease 1C), POLG (chronic progressive external ophthalmoplegia), APP (Alzheimer's disease) and OPTN (ALS12 ± FTD), and one RE in ATXN8OS (spinocerebellar ataxia 8). Additionally, two VUS were found in ANTXR2, a candidate gene for PLS recently identified via truncating variant collapsing analysis, but none of them was loss-of-function (one synonymous and one in-frame insertion).

CONCLUSIONS: Our study demonstrates a notable genetic intersection between PLS and various neurological disorders, including motor neuron diseases, neuropathies, mitochondrial disorders, ataxias, and dementias. These findings underscore the relevance of further investigation in larger cohorts to fully elucidate PLS genetic architecture and highlight the need to reconsider the role of genetic testing in its diagnostic criteria.}, } @article {pmid40843943, year = {2025}, author = {Musson, LS and Baxter, SK and Norman, P and O'Brien, D and Elliott, M and Bianchi, S and Kaltsakas, G and Mcdermott, CJ and Hobson, EV and Stavroulakis, T}, title = {Perceptions of healthcare professionals on optimal delivery of noninvasive ventilation care to people living with motor neuron disease.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {}, number = {}, pages = {1-8}, doi = {10.1080/21678421.2025.2539896}, pmid = {40843943}, issn = {2167-9223}, abstract = {Background: Patients with motor neuron disease (MND) often do not experience the full survival and quality of life benefits of noninvasive ventilation (NIV). Successful delivery of NIV is challenging to multiple healthcare professionals involved in the respiratory care patient journey and considering their perspectives is crucial in order to understand how to deliver optimal care. Objective: To identify the factors that influence NIV delivery in MND from a healthcare professional perspective and understand how obstacles can be overcome to optimize care. Methods: Qualitative focus group discussions with healthcare professionals delivering respiratory care and support to MND patients in the UK and charity representatives. Results: Thirty healthcare professionals and three charity representatives participated in five focus groups. A range of factors that influence the delivery of NIV across the entire respiratory care pathway were identified. These were grouped under four main themes: multidisciplinary working; NIV service structure; professional further education and training; and good use of NIV and effective ventilation. Conclusions: There is a need for specific resources to support service delivery; frequent, funded, and structured training to support healthcare professionals to deliver good care; as well as ways to encourage optimal staff practice so patients get the best care.}, } @article {pmid40843685, year = {2025}, author = {Epplen, ASC and Stahlke, S and Theiss, C and Matschke, V}, title = {Which One Would You Choose?-Investigation of Widely Used Housekeeping Genes and Proteins in the Spinal Cord of an Animal Model of Amyotrophic Lateral Sclerosis.}, journal = {NeuroSci}, volume = {6}, number = {3}, pages = {}, doi = {10.3390/neurosci6030069}, pmid = {40843685}, issn = {2673-4087}, abstract = {Amyotrophic lateral sclerosis (ALS) remains a progressive neurodegenerative disease, lacking effective causal therapies. The Wobbler mouse model harboring a spontaneous autosomal recessive mutation in the vacuolar protein sorting associated protein (Vps54), has emerged as a valuable model for investigating ALS pathophysiology and potential treatments. This model exhibits cellular and phenotypic parallels to human ALS, including protein aggregation, microglia and astrocyte activation, as well as characteristic disease progression at distinct stages. Exploring the underlying pathomechanisms and identifying therapeutic targets requires a comprehensive analysis of gene and protein expression. In this study, we examined the expression of three well-established housekeeping genes and proteins-calnexin, ß-actin, and ßIII-tubulin-in the cervical spinal cord of the Wobbler model. These candidates were selected based on their demonstrated stability across various systems like animal models or cell culture. Calnexin, an integral protein of the endoplasmic reticulum, ß-actin, a structural component of the cytoskeleton, and ß-tubulin III, a component of microtubules, were quantitatively assessed using quantitative reverse transcription-polymerase chain reaction (RT-PCR) for gene expression and Western blotting for protein expression. Our results revealed no significant differences in the expression of CANX, ACTB, and TUBB3 between spinal cords of wild-type and Wobbler mice at the symptomatic stage (p40) at both the gene and protein levels. These findings suggest that the pathophysiological alterations induced by the Wobbler mutation do not significantly affect the expression of these crucial housekeeping genes and proteins at p40. Overall, this study provides a basis for further investigations using the Wobbler mouse model, while highlighting the potential use of calnexin, ß-actin, and ßIII-tubulin as reliable reference genes and proteins in future research to aid in the discovery for effective therapeutic interventions.}, } @article {pmid40843608, year = {2025}, author = {Marshall, A and Goul, R and Dodson, B and Sakidja, R and Peelaers, H and Seacat, S and Bray, K and Ewing, D and Walsh, M and Wu, JZ}, title = {Probing the Effects of the First Atomic Layer on the Dynamic Behavior of Sub-2 nm MgO/Al2O3 Memristors.}, journal = {ACS applied materials & interfaces}, volume = {}, number = {}, pages = {}, doi = {10.1021/acsami.5c04654}, pmid = {40843608}, issn = {1944-8252}, abstract = {As electronic devices continue to scale down from the current sub-5 nm range, atomic-scale control of defects becomes increasingly crucial to suppressing their impact on the physical properties of the devices. Memristors present an excellent example of a nonlinear and dynamic device with high speed and endurance required for electronic applications ranging from neuromorphic computing to nonvolatile memories. Herein we investigate the impact of atomic defects in sub-2 nm thick MgO/Al2O3 atomic layer stack (ALS) memristors that use an M1 (switching layer)/M2 (oxygen vacancy reservoir layer) bilayer structure grown using in vacuo atomic layer deposition (iALD). Intriguingly, we revealed a direct correlation of the atomic defects in the M2 layer with the memristor dynamic behavior using combined analysis of in situ scanning tunneling spectroscopy (iSTS) on the M2 layer and ex situ characterization on the memristors. Specifically, incomplete coverage of the first ALD atomic layer of M2 on the electrode yields defects at the M2/electrode interface. Despite the monotonic increase of ALD coverage, by almost 3-fold from ∼30% to >90%, at completion of the M2 layer of ∼0.7 nm in thickness, the impact of the defects on the M2/electrode interface has been found to be detrimental to both memristor switching speed and endurance. Guided by atomistic simulation, we addressed the issue of interface defects via tuning of the Al surface hydroxylation to increase the first atomic layer ALD coverage to ∼75%, leading to improved memristor switching speed and endurance by several orders of magnitude. These findings shed light on the correlation between the atomic defects and the dynamic behavior of sub-2 nm memristors and the importance of minimizing the atomic defects in memristors for future electronic applications.}, } @article {pmid40842350, year = {2025}, author = {Long, JW and Hankins, DL and Adams, MM}, title = {Indigenous Fire Stewardship to Revitalize Disrupted Ecosystems.}, journal = {Global change biology}, volume = {31}, number = {8}, pages = {e70411}, doi = {10.1111/gcb.70411}, pmid = {40842350}, issn = {1365-2486}, mesh = {*Conservation of Natural Resources/methods ; *Wildfires ; *Ecosystem ; *Fires ; Australia ; Biodiversity ; }, abstract = {This commentary highlights the significance of Bowd et al.'s (2025) study with Wiradjuri and Ngunnawal community members in quantifying the effects of Indigenous Fire Stewardship on plant biocultural diversity in southeastern Australia's box-gum grassy woodlands. Their work is a model for bridging ecological science and Indigenous stewardship in restoring fire-adapted ecosystems. Accelerating and scaling such efforts can counter the disruption of Indigenous practices, the spread of nonnative species, the intensification of wildfires, and other global changes.}, } @article {pmid40841847, year = {2025}, author = {Du, C}, title = {Selection bias, overfitting, and generalisability in predicting postoperative complications: insights from Fang et al.'s work.}, journal = {Journal of robotic surgery}, volume = {19}, number = {1}, pages = {504}, pmid = {40841847}, issn = {1863-2491}, } @article {pmid40841608, year = {2025}, author = {Snow, M and Cameron, B and Pond, R and Trudell, R and Snyder, S and Torres-Hernandez, L and Deschamps, D and Tulimaiau, D and Hawkinson, K and Russell, M and Horan, D and Walters, J and Fox, JH and Arlian, B and Chariot, A and Nguyen, L and George, L}, title = {An Elongator mouse model of ALS spotlights TDP-43 in the motor neuron nucleolus.}, journal = {Communications biology}, volume = {8}, number = {1}, pages = {1259}, pmid = {40841608}, issn = {2399-3642}, support = {R15NS090384//U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; P20GM103474//U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)/ ; }, mesh = {Animals ; *Amyotrophic Lateral Sclerosis/metabolism/genetics/pathology ; *Motor Neurons/metabolism/pathology ; *Cell Nucleolus/metabolism ; *DNA-Binding Proteins/metabolism/genetics ; Disease Models, Animal ; Mice ; Mice, Knockout ; Humans ; Spinal Cord/metabolism/pathology ; }, abstract = {Dysfunction of Elongator is associated with amyotrophic lateral sclerosis (ALS). Here, we describe mouse models in which either Elongator subunit 1(Elp1) or subunit 3 (Elp3) is selectively ablated in alpha motor neurons of the spinal cord. These mice exhibit a progressive loss of motor strength and motor neuron degeneration. To interrogate the molecular mechanisms that contribute to motor neuron cell death in these mice, we examine multiple disease pathways, including the expression of TDP-43 whose cytoplasmic aggregation is associated with the human disease. Although TDP-43 is a well-characterized nuclear protein functioning in RNA metabolism and gene transcription, here we document TDP-43's robust presence in the nucleolus of wild-type motor neurons and its clearance from both the nucleus and the nucleolus of motor neurons in Elp conditional knockout mice. Thus, this study directly links dysfunction of Elongator with nucleolar disruption and TDP-43 clearing, two hallmark cellular pathologies of ALS.}, } @article {pmid40841583, year = {2025}, author = {Watanabe, K and Ema, T and Shimizu, K and Yamada, K and Nakashima, M and Saitsu, H}, title = {A Japanese familial spastic paraplegia associated with a missense UBQLN2 variant.}, journal = {Journal of human genetics}, volume = {}, number = {}, pages = {}, pmid = {40841583}, issn = {1435-232X}, support = {JP23K27566//MEXT | Japan Society for the Promotion of Science (JSPS)/ ; JP25ek0109760//Japan Agency for Medical Research and Development (AMED)/ ; JP25ek0109674//Japan Agency for Medical Research and Development (AMED)/ ; JP25ek0109637//Japan Agency for Medical Research and Development (AMED)/ ; }, abstract = {UBQLN2 is located on Xp11.21 and encodes the ubiquilin 2 protein involved in protein homeostasis. Heterozygous or hemizygous missense variants in UBQLN2 cause amyotrophic lateral sclerosis (ALS). In addition, rare cases of primary lateral sclerosis (PLS) and spastic paraplegia (SPG) associated with UBQLN2 variants have also been reported. Here, we report four male patients in a family with SPG carrying a hemizygous missense UBQLN2 variant (NM_013444.4:c.1442G>T, p.(Gly481Val)). These patients showed childhood-onset lower limb spasticity, progressing to gait disturbance. The mean onset age (11 years) was earlier than that of previous ALS (49.6 years), SPG (29 years) and PLS (25.5 years) cases, and their progression was slower than in ALS or PLS. Literature review reveals Pro506 missense variants are associated with various motor neuron disease phenotypes, with some SPG patients progressing to ALS. Therefore, we consider that careful follow-up is warranted for UBQLN2-related SPG patients.}, } @article {pmid40841001, year = {2025}, author = {Zheng, X and Jia, G and Zhao, Y and Yan, T}, title = {Involvement of four alga toxins in the risks of human neurodegenerative diseases: Toxicogenomic data mining and bioinformatics analysis.}, journal = {Journal of environmental sciences (China)}, volume = {158}, number = {}, pages = {151-164}, doi = {10.1016/j.jes.2025.02.036}, pmid = {40841001}, issn = {1001-0742}, mesh = {Humans ; *Neurodegenerative Diseases/chemically induced/epidemiology ; Computational Biology ; *Marine Toxins/toxicity ; Toxicogenetics ; Data Mining ; Amino Acids, Diamino/toxicity ; Okadaic Acid/toxicity ; Oxocins/toxicity ; Cyanobacteria Toxins ; Microcystins ; }, abstract = {Alga toxins have recently emerged as an environmental risk factor, especially to neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis. However, the association between the alga toxins β-N-methylamino-L-alanine (BMAA), brevetoxin B, cyanoginosin LR, okadaic acid and neurodegenerative diseases remains inadequately investigated. Therefore, the aim of this study was to elucidate the potential associations. Four sets of differentially expressed genes related with BMAA, brevetoxin B, cyanoginosin LR and okadaic acid in Homo sapiens and genes linked to neurodegenerative disease development were respectively collected from the Comparative Toxicogenomic Database. Metascape analysis and cluster community analysis of four alga toxins highlighted protein-protein interaction enrichment and hub genes, while biological processes analysis showed that the dominant pathways involved in harmful effects triggered by four alga toxins were the apoptotic signaling pathway, regulation of amyloid protein formation, inflammatory response and endoplasmic reticulum stress. Genes related to the interactions between four alga toxins and neurodegenerative diseases were selected and analyzed, revealing that the relevant pathways and genes were those involved in apoptotic mitochondrial changes and neuroinflammatory response pathways. The adverse outcome pathway frameworks were constructed according to the analysis results for toxins and associated neurodegenerative diseases. These discoveries provide a new perspective for us to gain a deeper understanding of the neurotoxic effects of four alga toxins.}, } @article {pmid40840854, year = {2025}, author = {Fernàndez-Bernal, A and Mota, N and Pamplona, R and Area-Gómez, E and Portero-Otin, M}, title = {Mission cholesterol: Uncovering its hidden role in ALS neurodegeneration.}, journal = {Biochimica et biophysica acta. Molecular basis of disease}, volume = {}, number = {}, pages = {168021}, doi = {10.1016/j.bbadis.2025.168021}, pmid = {40840854}, issn = {1879-260X}, abstract = {Cholesterol is a central determinant of membrane architecture, signaling, and cellular homeostasis in the central nervous system (CNS). While historically viewed as a structural component, emerging evidence highlights its dynamic regulatory role in neuronal function, particularly through its compartmentalized synthesis, trafficking, and turnover. This review examines the complex landscape of cholesterol metabolism in the CNS, emphasizing the cooperative roles of astrocytes and neurons, the partitioning of biosynthetic pathways, and the barriers that distinguish brain cholesterol pools from peripheral sources. We focus on mitochondria-associated endoplasmic reticulum membranes (MAMs) as key regulatory platforms for cholesterol sensing, esterification, and signaling, underscoring their emerging role in neurodegenerative diseases. Disruptions in MAM integrity, lipid raft composition, and transcriptional regulation of cholesterol-handling genes have been linked to pathologies such as amyotrophic lateral sclerosis (ALS), particularly through the actions of TDP-43. By consolidating recent findings from lipidomics, cell biology, and disease models, we propose that cholesterol dyshomeostasis constitutes a shared mechanistic axis across diverse neurodegenerative conditions. Understanding this axis offers novel insights into the metabolic vulnerability of neurons and highlights cholesterol metabolism as a promising target for therapeutic intervention.}, } @article {pmid40839404, year = {2025}, author = {Li, Z and Jiang, J and Song, J and Bai, L and Pan, L}, title = {One Glutathione S-Transferase Gene, GSTU163, Was Involved in Mesosulfuron-methyl Resistance in Alopecurus japonicus.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.5c08615}, pmid = {40839404}, issn = {1520-5118}, abstract = {Alopecurus japonicus, an annual grass damaging wheat and canola fields in China, has evolved resistance to mesosulfuron-methyl, an acetolactate synthase (ALS)-inhibiting herbicide commonly used for its control. In this study, the resistant population (R) exhibited 22.93-fold resistance to mesosulfuron-methyl, and single-dose screening revealed cross-resistance to five other ALS-inhibiting herbicides. ALS gene sequencing revealed no known resistance mutations. Pretreatment with the glutathione S-transferase (GST) inhibitor 4-chloro-7-nitrobenzoxadiazole (NBD-Cl) increased the sensitivity of the R population to mesosulfuron-methyl. RNA-seq and quantitative real-time polymerase chain reaction (RT-qPCR) identified significant upregulation of one cytochrome P450 gene, two GST genes, and three glycosyltransferase genes, with AjGSTU163 showing the highest upregulation in the R population. Heterologous expression of AjGSTU163 in yeast significantly enhanced growth on mesosulfuron-methyl-containing media by mitigating ROS accumulation. Knockout of rice homologue OsGSTU163 slightly increased sensitivity to mesosulfuron-methyl in rice. This study first reported that GST contributes to mesosulfuron-methyl resistance in A. japonicus.}, } @article {pmid40839108, year = {2025}, author = {Mukherjea, N and Khandelwal, A and Saluja, R and Kalra, N}, title = {The Role of the human microbiome in neurodegenerative diseases: A Perspective.}, journal = {Current genetics}, volume = {71}, number = {1}, pages = {17}, pmid = {40839108}, issn = {1432-0983}, mesh = {Humans ; *Neurodegenerative Diseases/microbiology ; *Microbiota ; Parkinson Disease/microbiology ; *Gastrointestinal Microbiome ; Alzheimer Disease/microbiology ; Inflammasomes ; Inflammation/microbiology ; }, abstract = {Advances in diagnostics, therapeutics, and large-scale clinical studies have significantly expanded our understanding how human health is shaped by the microorganisms that colonize the body since birth. This article explores the rapidly evolving field of human microbiome research, focusing upon how microbial communities influence neurological health and contribute to the development of neurodegenerative diseases (NDs). Multiple factors, including age, lifestyle, and immunological memory, are recognized as major determinants of an individual's microbiome composition, which in turn can influence the onset and the progression of disorders such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. These conditions have been linked to mechanisms including the aggregation of pathogenic proteins (e.g., amyloid-β and α-synuclein), inflammation driven by activation of the Toll-like receptor (TLR) signaling pathway, the NLRP3 inflammasome, as well as the modulatory effect of microbial metabolites such as short-chain fatty acids (SCFAs) and lipopolysaccharides (LPS). The article also highlights ongoing research and emerging strategies aimed at leveraging the human microbiome for better diagnosis, and management of NDs.}, } @article {pmid40838943, year = {2025}, author = {Hiraoka, T and Tamura, M and Moriguchi, Y and Kuji, R and Mino, T and Akiba, M and Takahashi, Y and Yoshino, K and Suzaki, A and Sugimoto, K and Oshika, T}, title = {Choroidal Thickness Distribution and Its Association With Axial Length and Spherical Equivalent in Schoolchildren Assessed by Wide-Field Swept-Source Optical Coherence Tomography.}, journal = {Translational vision science & technology}, volume = {14}, number = {8}, pages = {33}, doi = {10.1167/tvst.14.8.33}, pmid = {40838943}, issn = {2164-2591}, mesh = {Humans ; *Tomography, Optical Coherence/methods ; Child ; *Choroid/diagnostic imaging/anatomy & histology ; Adolescent ; Female ; Male ; Prospective Studies ; *Axial Length, Eye/diagnostic imaging ; Myopia ; }, abstract = {PURPOSE: The purpose of this study was to evaluate the distribution of choroidal thickness (ChT) in schoolchildren using wide-field swept-source optical coherence tomography (SS-OCT) and to investigate its association with axial length (AL) and spherical equivalent (SE).

METHODS: This prospective study included 176 eyes from 88 healthy Japanese schoolchildren aged 6 to 15 years (mean age = 9.9 ± 2.4 years). Wide-field SS-OCT was used to measure ChT across a 57 degrees × 57 degrees fundus area. After excluding poor-quality images, 169 eyes were included in the final analysis. The ChT distribution was evaluated by dividing the obtained images into a 3 × 3 grid comprising 9 sections. ChT measurements were performed automatically with custom-designed software. ChT values were compared among the nine regions, and correlations with AL and SE were assessed for each grid section. Additionally, the findings in schoolchildren were compared with historical data from adults.

RESULTS: Mean ChT values across the 9 regions ranged from 172 ± 29 µm in the nasal-inferior region to 307 ± 39 µm in the temporal region. The choroid was thicker in the temporal and macular regions and thinner around the optic disc and inferior regions. Significant negative correlations were found between ChT and AL across all regions (R = -0.50 to -0.23, P < 0.05), indicating that longer ALs were associated with thinner choroids. Similarly, significant positive correlations were observed between ChT and SE (R = 0.19 to 0.55, P < 0.05), demonstrating that higher degrees of myopia were associated with thinner choroids. Moreover, ChT in schoolchildren was generally thicker compared to that in adults.

CONCLUSIONS: This study provides a detailed analysis of ChT distribution in schoolchildren, revealing regional variability and a generally thicker choroid compared with adults. The significant correlations between ChT, AL, and SE across all regions suggest a potential role for ChT in ocular growth and myopia progression. These findings underscore the need for longitudinal studies to investigate causal relationships between ChT distribution and myopia development.

TRANSLATIONAL RELEVANCE: Wide-field choroidal mapping identifies early structural biomarkers for pediatric myopia progression and control.}, } @article {pmid40838713, year = {2025}, author = {Noor, SM and Reddy, DH and Srikanth, Y and Viswanadh, MK and Dumala, N and Chakravarthy, G and Nalluri, BN and Naryanarao, A and Duguluri, S and Yadagiri, G and Prasanna, VS and Sundaram, S and Gujjari, L and Ramakrishna, K}, title = {Morin hydrate: a comprehensive review on therapeutic potential in treating neurological diseases.}, journal = {Nutritional neuroscience}, volume = {}, number = {}, pages = {1-25}, doi = {10.1080/1028415X.2025.2544605}, pmid = {40838713}, issn = {1476-8305}, abstract = {Background: Morin hydrate is a polyphenolic flavonoid present in various vegetables, fruits, nuts, and sea products. It has been reported to offer multiple protective effects against a range of diseases, including cancer, cardiovascular, liver, neurological, metabolic, and renal disorders.Objective: This review highlights the molecular mechanisms and therapeutic potential of Morin in neurological diseases, including Parkinson's disease, Alzheimer's disease, traumatic brain injury, neuropathic pain, stroke, Huntington's disease, multiple sclerosis, amyotrophic lateral sclerosis, depression, anxiety, sleep, encephalopathy, schizophrenia, and psychosis, etc.Methods: The research and review articles were collected from the Pubmed, Scopus, Web of Science, and Google Scholar databases using 'Morin' and the above-mentioned neurological diseases as keywords.Results: The neuroprotective effects of Morin are primarily attributed to its ability to mitigate oxidative stress, inflammation, excitotoxicity, calcium dysregulation, mitochondrial dysfunction, neurotransmitter alterations, protein modifications, and enzymatic inhibition.Conclusion: Despite its promising pharmacological profile, the clinical adaptation of Morin for combating neurological diseases requires further validation through comprehensive preclinical and clinical investigations.}, } @article {pmid40838580, year = {2025}, author = {Tse, NY and Caga, J and Ahmed, RM and Mazumder, S and Nguyen, C and Huynh, W and Karjalainen, A and Timmins, HC and Ramsey, E and Talbot, DL and Halliday, GM and Kiernan, MC and Devenney, EM}, title = {Behavioral subtypes impact prognosis and survival in amyotrophic lateral sclerosis: a clustering-based approach.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {}, number = {}, pages = {1-10}, doi = {10.1080/21678421.2025.2522402}, pmid = {40838580}, issn = {2167-9223}, abstract = {BACKGROUND: Behavioral impairments are well established in amyotrophic lateral sclerosis (ALS). A refined understanding of the contribution of delineated patterns of behavioral impairments to prognosis is vitally important.

METHODS: Leveraging data-driven two-step cluster analysis, we first stratified a large cross-sectional cohort of 170 ALS patients into distinct phenotypic subtypes based on their baseline behavioral profiles, as determined by the well-validated and informant-rated Motor Neuron Disease Behavioral Instrument (MiND-B). Mixed-effects model and multivariate Cox regression analyses were performed to compare rate of functional decline as measured by the revised ALS functional rating scale (ALSFRS-R) over follow-up assessments in 121 participants, as well as survival duration (n = 130), between the behavioral subtypes. Results: Clustering analysis yielded three behavioral phenotypes characterized by 1) intact behavioral functioning (n = 125), 2) apathy alone (n = 20), and 3) concurrent disinhibition and stereotypical behavior (n = 25). Apathy was associated with both significantly shorter survival (p = .003) and most rapid functional decline across follow-up assessments (both p <.001). Importantly, this pervasive effect was not observed in other behavioral cluster groups.

CONCLUSIONS: Extending previous cross-sectional work, current findings offer delineation of the trajectory of clinical outcomes associated with classic behavioral phenotypes of ALS. Converging with past evidence of unique disease and progression profile in ALS patients with apathy, our work provides strong support for behavioral change and in particular apathy as a reliable indicator of poor prognosis across cross-sectional and longitudinal markers of clinical outcomes.}, } @article {pmid40837865, year = {2025}, author = {Khan, H and Riaz, H and Ahmed, A and Kiyani, MM and Jawad, SM and Ud Din Shah, SS and Abualait, T and Al-Hussain, F and Li, HT and Bashir, S}, title = {CRISPR/Cas9 a genomic engineering technology for treatment in ALS mouse models.}, journal = {Regenerative therapy}, volume = {30}, number = {}, pages = {575-583}, pmid = {40837865}, issn = {2352-3204}, abstract = {Amyotrophic Lateral Sclerosis (ALS) is a complex neurodegenerative disorder characterized by the death of motor neurons in the spinal cord and brain regions, leading to a reduced survival rate in patients. Nearly 20 gene mutations are associated with ALS, with SOD1, FUS, TARDBP, and C9orf72 mutations being more common. Ninety percent of ALS cases are related to sporadic ALS, while the remaining 10 % are associated with familial ALS. CRISPR/Cas9, a genome engineering technology known as clustered regularly interspaced short palindromic repeats/CRISPR-associated system 9, has the potential for gene editing and for studying the underlying mechanisms of ALS in mouse models. This technique enables neuroscientists to reverse mutations found in ALS mouse models, providing new hope for understanding the complexities of ALS. Additionally, this tool can create mutations to probe the functional changes of genetic diseases. Using CRISPR/Cas9 with an in vivo delivery method involving adeno-associated vectors, it is possible to silence mutations in the SOD1-linked ALS mouse model. Some limitations related to CRISPR/Cas9 have been discussed in previous studies and need to be addressed before clinical trials can proceed. In this review-based study, we summarise the latest research on CRISPR/Cas9 genome editing for ALS in mouse models and discuss its limitations and future prospects as well.}, } @article {pmid40837837, year = {2025}, author = {Zhao, S and Chen, R and An, Y and Zhang, Y and Ma, C and Gao, Y and Lu, Y and Yang, F and Bai, X and Zhang, J}, title = {Correction: Optineurin overexpression ameliorates neurodegeneration through regulating neuroinflammation and mitochondrial quality in a murine model of amyotrophic lateral sclerosis.}, journal = {Frontiers in aging neuroscience}, volume = {17}, number = {}, pages = {1670545}, doi = {10.3389/fnagi.2025.1670545}, pmid = {40837837}, issn = {1663-4365}, abstract = {[This corrects the article DOI: 10.3389/fnagi.2025.1522073.].}, } @article {pmid40836724, year = {2025}, author = {Gupta, S and Tomar, S and Soni, R and Anadure, R and Somashekhar, M and Singhal, A}, title = {Efficacy and Safety of Edaravone in Amyotrophic Lateral Sclerosis: It is Safe but Does Not Stop Progression.}, journal = {The Journal of the Association of Physicians of India}, volume = {73}, number = {7}, pages = {68-71}, doi = {10.59556/japi.73.1044}, pmid = {40836724}, issn = {0004-5772}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy ; *Edaravone/therapeutic use/adverse effects/administration & dosage ; Middle Aged ; Male ; Female ; Prospective Studies ; Disease Progression ; Riluzole/therapeutic use/administration & dosage ; Aged ; Adult ; India ; *Free Radical Scavengers/therapeutic use/adverse effects/administration & dosage ; Treatment Outcome ; Neuroprotective Agents/therapeutic use/administration & dosage ; }, abstract = {BACKGROUND: Edaravone is recommended for amyotrophic lateral sclerosis (ALS) based on a study showing an effect on a defined subset of patients.

AIM: To document the effect of edaravone in a cohort of ALS patients from India to find out if, after starting edaravone, there is a plateau period or significant slowing from baseline to compare results with existing literature.

METHODS: This was a single-center, prospective observational study with no control arm (due to ethical reasons). ALS patients >18 years of age, not requiring respiratory support or tube feeding, were included. All patients were given edaravone infusion in addition to standard of care and oral riluzole 50 mg twice daily. This consisted of giving the drug in monthly cycles over 6 months. The first cycle consisted of daily infusion of the drug for 14 days followed by a drug-free interval for the remaining part of the month. From cycle 2 to cycle 6, the patients received the drug for the first 10 days of the month followed by a drug-free interval for the remaining part of the month. The primary outcome was a significant change in Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) score from baseline at 6 months. Secondary outcomes were monthly change in ALSFRS-R scores when compared with the previous month and baseline, change in the first 3 months compared to the change in the next 3 months, adverse drug effects, and number of deaths. The study was registered with the Indian Council of Medical Research Clinical Trial Registry of India with the trial number CTRI/2019/11/021838. Paired t-test was used for statistical analysis.

RESULTS: Thirty patients received the drug along with riluzole. Twenty-three patients completed all six monthly infusions. Two died (3 months), two developed adverse reactions (3 months) and did not want further infusions (one had breathing difficulty and the other had hypotension during infusion). Two withdrew consent due to perceived poor effectiveness of the drug. The mean ALSFRS-R at baseline was 35.17 [standard deviation (SD) 8.01; range 20-46]. The primary outcome showed a significant decline in the mean last available ALSFRS-R score 6 months by -4.9 (SD 1.21) (p < 0.01). For the secondary outcome measure, mean monthly ALSFRS-R score was calculated before each infusion after excluding dropouts. There was a significant monthly decline in ALSFRS-R score: -0.93 (SD 0.58), -1.0 (-0.52), -0.90 (SD 0.71), -0.87 (SD 0.61), -0.82 (SD 0.57), -0.95 (SD 0.63), respectively (p < 0.001). There was also a progressive monthly decline when compared to baseline. The rate of decline in the first 3 months was the same as in the remaining 3 months: -2.5 (SD 0.73) vs -2.6 (SD 0.98) (p = 0.3).

CONCLUSION: Edaravone infusion does not stop or significantly slow progression of disease from baseline but is safe.}, } @article {pmid40835551, year = {2025}, author = {Rajsic, S and Treml, B and Breitkopf, R and Lederer, W}, title = {Ethical Considerations for Patients Requiring Extracorporeal Cardiopulmonary Resuscitation.}, journal = {Journal of cardiothoracic and vascular anesthesia}, volume = {}, number = {}, pages = {}, doi = {10.1053/j.jvca.2025.07.032}, pmid = {40835551}, issn = {1532-8422}, abstract = {Immediate recognition of cardiac arrest and the initiation of cardiopulmonary resuscitation (CPR) can significantly improve survival chances. The use of extracorporeal membrane oxygenation during CPR (eCPR) could further enhance survival rates. Current evidence supports the implementation of eCPR as a part of the Advanced Life Support protocol, which may positively affect survival and long-term neurological outcomes and provide additional time for diagnosing and treating the underlying cause of cardiac arrest. Based on the patient's potential for recovery and neurological outcome, multidisciplinary teams can pursue weaning of the patient from mechanical support or withdrawal of care in the case of an unfavorable outcome. These decisions should align with the patient's values, prognosis, and ethical guidelines. A healthcare system that actively promotes eCPR as a standardized part of every Advanced Life Support protocol may face challenges, such as an increased number of patients requiring constant care in long-term care facilities. This could potentially lead to a reduced quality of life and create burdens on patients, families, the healthcare system, and society. Furthermore, in cases of potential organ donation, the principles of beneficence and autonomy may place healthcare providers in significant ethical dilemmas. Given the potential for eCPR to become a standard of care for eligible patients, this work focuses on the ethical and social implications, as well as the impact on the healthcare system.}, } @article {pmid40834778, year = {2025}, author = {Wang, X and Madihie, AB and Sze, SN}, title = {Translation and psychometric evaluation of the Chinese version of the mathematical resilience scale.}, journal = {Acta psychologica}, volume = {259}, number = {}, pages = {105412}, doi = {10.1016/j.actpsy.2025.105412}, pmid = {40834778}, issn = {1873-6297}, abstract = {The translation of the Mathematics Resilience Scale (MRS) into Chinese provides an essential tool for educational research within Chinese cultural contexts, and this study supports educators in identifying emotional and cognitive barriers that students encounter in mathematics learning, thereby enabling targeted interventions. This study focuses on translating the MRS into Chinese and evaluating its reliability and validity within the Chinese context. The translation adhered to Beaton et al.'s (2000) guidelines, with validity and reliability assessed through item analysis, reliability analysis, validity analysis, item response theory, and differential item functioning. The Cronbach's α value for the MRS was .969, indicating strong performance, while item factor loadings ranged from .514 to .859, and the Kaiser-Meyer-Olkin value was .968. The Chinese version of the MRS has been accurately and thoroughly translated, demonstrating robust psychometric properties. This study provides a quantitative instrument for addressing resilience-related issues in mathematics education, offering valuable data to inform interventions for policymakers and educators. The study significantly contributes to ensuring the cross-cultural applicability and validity of the MRS, offering a reliable tool for international research on mathematical resilience.}, } @article {pmid40834467, year = {2025}, author = {Bocquier, A and Simon, M and Michel, M and Bonnay, S and Adam, I and Gilberg, S and Bruel, S and Gauchet, A and LeDuc-Banaszuk, AS and Gagneux-Brunon, A and Mueller, JE and Giraudeau, B and Thilly, N and , }, title = {Implementation evaluation of a school- and primary care-based multicomponent intervention to improve HPV vaccine coverage: Results from the PrevHPV randomized controlled trial.}, journal = {Journal of infection and public health}, volume = {18}, number = {11}, pages = {102931}, doi = {10.1016/j.jiph.2025.102931}, pmid = {40834467}, issn = {1876-035X}, abstract = {BACKGROUND: Human papillomavirus (HPV) vaccine coverage (VC) remains lower than expected in France. The PrevHPV national research program aimed to codevelop and evaluate an intervention including three components: 'education and motivation' of adolescents in schools, 'at-school vaccination', 'general practitioners (GPs)' training'. This study aimed to evaluate the implementation outcomes of each component, whether they affected effectiveness, and identify factors influencing implementation in schools.

METHODS: A mixed-method study embedded in a cluster randomized controlled trial in 91 French municipalities (July 2021-June 2022). Quantitative data were collected through activity reports and questionnaires, and qualitative data through focus groups with school staff. The implementation outcomes were fidelity, dose, reach, acceptability and sustainability, as defined in the Medical Research Council guidance for process evaluation of complex interventions and Proctor et al.'s Implementation Outcomes Framework; the effectiveness outcome was HPV VC (≥ 1 dose) two months after the end of the intervention. Qualitative data were analyzed using the Consolidated Framework for Implementation Research.

RESULTS: The fidelity, acceptability, and sustainability of all three components among participants who completed the intervention were high. However, the withdrawal of one-third of schools before the trial started and difficulties in mobilizing GPs negatively impacted the dose and reach outcomes. Estimates for the on-treatment analyses of the effectiveness were greater than those for which the dose of intervention received was not considered; 'at-school vaccination' (11.25 percentage points, p < 0.001) and 'GPs' training' (3.56 percentage points, p = 0.049) increased VC, while 'education and motivation' remained nonsignificant.

CONCLUSIONS: Increasing HPV VC among adolescents could be achieved by combining interventions in both schools and primary care settings. This study provides practical implications for implementing such interventions in real life.

TRIAL REGISTRATION: Clinicaltrials.gov, NCT04945655. Registered 30 June 2021, https://clinicaltrials.gov/study/NCT04945655.}, } @article {pmid40833646, year = {2025}, author = {Das, B and Baruah, SMB and Roy, S and Bhattacharyya, DK}, title = {An effective framework to study signal transmission due to non-homogeneous extracellular space in neuron.}, journal = {Journal of biological physics}, volume = {51}, number = {1}, pages = {24}, pmid = {40833646}, issn = {1573-0689}, mesh = {*Extracellular Space/metabolism ; *Neurons/cytology/metabolism/physiology ; Neural Conduction ; *Models, Neurological ; Humans ; }, abstract = {Nerve conduction velocity studies are essential to understanding neurological disorders like ALS, Guillain-Barré syndrome, Charcot-Marie-Tooth disease, carpal tunnel syndrome, sciatic nerve disorders, and multiple sclerosis, which are marked by slowed signal conduction. Various ions in the extracellular space (ECS) and the nerve fiber regulate signal propagation, making it crucial to analyze ECS's impact on signal transmission. This study examines how a non-homogeneous extracellular space affects nerve conduction velocity using a modified cable model that incorporates ECS parameters such as its diameter and resistance. The results suggest that a non-homogeneous extracellular space significantly impacts the conduction velocity of propagating signals, leading to variations in the conduction velocity, signal delays, phase shifts, and resonance. The model has been thoroughly examined using various combinations of electrophysiological parameters of the ECS and nerve fibers to simulate a wide range of biological conditions, and the simulated results have been consistent and align with the existing findings.}, } @article {pmid40833060, year = {2025}, author = {Serrato-Diaz, LM and Cuevas, HE and Chilagane, LA and Rosas, JC and Velez, JM and Schadt, CW and Rivera-Vargas, LI and Bayman, P and Porch, TG}, title = {Population Genomics of Pseudocercospora griseola Reveals New Groups in the Middle American Clade and the Presence of the Endophytic Bacterium Achromobacter xylosoxidans.}, journal = {Phytopathology}, volume = {}, number = {}, pages = {}, doi = {10.1094/PHYTO-09-24-0302-R}, pmid = {40833060}, issn = {0031-949X}, abstract = {Angular leaf spot (ALS), caused by Pseudocercospora griseola is an important disease of common beans. P. griseola, is highly variable and has co-evolved with its host. In this study, 48 isolates of P. griseola from Puerto Rico, Guatemala, Honduras and Tanzania were sequenced (3RADseq), resulting in the de novo assembly of 42,214 contigs. Phylogenomic, population genetic structure and principal component analyses using 1,260 SNPs divided these isolates into two populations, Andean and Middle American, while the Middle American population was further divided into three sub-populations. There were moderate to high levels of differentiation between P. griseola populations, with pairwise Fst values ranging from 0.11 to 0.95. The Andean population was composed of isolates from Tanzania, and was separated from the Middle American population (Fst = 0.95). The Middle American population was separated into 3 subpopulations including isolates from: 1. Guatemala and Honduras, 2. Tanzania, and 3. Puerto Rico. Pathogenicity testing of 27 isolates from Puerto Rico, using 12 common bean differential lines, identified ten races, but these races were not associated with SNPs found in virulence genes. DNA of an endophytic bacterium (Achromobacter xylosoxidans) was found in seven mildly virulent isolates suggesting a possible role of the bacterium in the observed virulence patterns. To understand the evolution and diversity of P. griseola, further study of the virulence genes and the interactions among the endophytic bacterium, the fungus, and the host plant is required. Such information is critical to inform breeding strategies for the development of resistant germplasm and cultivars.}, } @article {pmid40833010, year = {2025}, author = {Schuster, NM and Broachwala, M and Ahadian, FM and Argoff, CE and Cohen, SP and Durbhakula, S and Gulati, A and Hurley, RW and Kohan, L and McCormick, ZL and Wahezi, SE and Barreveld, AM}, title = {Reply to Wang et al.'s Reply to "Notable Concerns in Methodology and Conclusions of the Wang et al. Meta-Analysis in BMJ by the American Academy of Pain Medicine" by Schuster et al.}, journal = {Pain medicine (Malden, Mass.)}, volume = {}, number = {}, pages = {}, doi = {10.1093/pm/pnaf108}, pmid = {40833010}, issn = {1526-4637}, } @article {pmid40832964, year = {2025}, author = {Chen, WL and Wei, LC}, title = {Cross-Cultural Reflections on Community Mental Health Centres: Lessons From Turkey for Taiwan and Beyond.}, journal = {Journal of psychiatric and mental health nursing}, volume = {}, number = {}, pages = {}, doi = {10.1111/jpm.70020}, pmid = {40832964}, issn = {1365-2850}, abstract = {BACKGROUND: Salik et al.'s phenomenological study documents the emotional, social and economic challenges faced by Turkish service-users of Community Mental Health Centres (CMHCs).

OBJECTIVE: To contextualise those findings within Taiwan's CMHC system and highlight universal priorities for culturally responsive care.

CONTENT: Drawing on Taiwanese qualitative studies and regional literature, the letter underscores persistent stigma, limited vocational opportunities and fragmented continuity of care. Evidence from Taiwan mirrors Turkish operational barriers, while employment research and deinstitutionalisation analyses reinforce the need for family-inclusive, vocationally oriented interventions. International data on religiosity in caregiving and psychosocial skills training illustrate transferable strategies for stigma reduction and functional recovery.

IMPLICATIONS: CMHCs worldwide should integrate anti-stigma campaigns, spiritual or cultural supports and structured vocational rehabilitation to enhance recovery and social inclusion.

CONCLUSION: Shared challenges demand globally informed yet locally adapted community mental health policies.}, } @article {pmid40832750, year = {2025}, author = {Erdi-Krausz, G and Shaw, PJ}, title = {Antisense oligonucleotide therapy in amyotrophic lateral sclerosis.}, journal = {Current opinion in neurology}, volume = {}, number = {}, pages = {}, doi = {10.1097/WCO.0000000000001413}, pmid = {40832750}, issn = {1473-6551}, abstract = {PURPOSE OF REVIEW: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder with few treatment options available. The approval of tofersen, an antisense oligonucleotide, for SOD1-ALS by the FDA and EMA may herald a new era of treatment in these patients.

RECENT FINDINGS: So far, trials against the most common genetic form of ALS, C9orf72, have been unsuccessful, but new preclinical data may show a promising new direction to take. Clinical trials targeting other, more rare genetic mutations associated with familial ALS are currently underway. Other research assessing the use of ASOs to target aberrant splicing associated with sporadic forms of ALS has also produced promising results in preclinical models, using patient-derived induced cellular models and animal models. These therapies are focussed largely on alleviating and reversing TDP-43 pathology, opening up the possibility of not only arresting disease progression, but reversing neurodegeneration.

SUMMARY: ASO therapies have made some promising steps towards treating familial ALS, particularly SOD1. Ongoing early clinical/preclinical phase research is underway to utilise this technology in other genetic mutations linked with ALS, as well as in sporadic cases.}, } @article {pmid40832743, year = {2025}, author = {Verde, F}, title = {Neurochemical biomarkers of amyotrophic lateral sclerosis: recent developments.}, journal = {Current opinion in neurology}, volume = {}, number = {}, pages = {}, doi = {10.1097/WCO.0000000000001411}, pmid = {40832743}, issn = {1473-6551}, abstract = {REVIEW PURPOSE: To provide an overview of the recent developments in the field of neurochemical biomarkers of amyotrophic lateral sclerosis (ALS).

RECENT FINDINGS: Neurofilaments, especially NFL, have been confirmed to be good biomarkers for ALS. NFL may be diagnostically useful but its main role is as prognostic and pharmacodynamic biomarker. Inflammatory biomarkers, especially the chitinases, might also serve as pharmacodynamic biomarkers in treatment trials targeting neuroinflammation. GFAP could reflect cognitive-behavioural impairment. CSF dipeptides are diagnostic biomarkers for ALS caused by the C9ORF72 exanucleotide repeat expansion and may be used to confirm target engagement by experimental drugs. Levels of TDP-43 (virtually the ideal biomarker for ALS) in CSF and plasma have not been demonstrated to be consistently altered in ALS. However, promising advancements have been achieved in seed amplification assays for the protein, in its quantification in plasma extracellular vesicles, and in the measurement of CSF levels of a protein reflecting splicing dysfunction of TDP-43. Finally, blood phosphorylated tau has emerged as an ALS biomarker linked to lower motor neuron (or muscle) pathology.

SUMMARY: NFL is still the best neurochemical biomarker for ALS. However, substantial advances have been recently made, especially regarding detection of TDP-43 and blood phosphorylated tau.}, } @article {pmid40832740, year = {2025}, author = {Lang, C}, title = {Sleep alterations in amyotrophic lateral sclerosis.}, journal = {Current opinion in neurology}, volume = {}, number = {}, pages = {}, doi = {10.1097/WCO.0000000000001424}, pmid = {40832740}, issn = {1473-6551}, abstract = {PURPOSE OF REVIEW: This review summarizes recent evidence on sleep disturbances in amyotrophic lateral sclerosis (ALS), emphasizing their role as intrinsic features of the disease process rather than consequence of motor decline.

RECENT FINDINGS: Emerging data suggest that sleep disturbances such as sleep fragmentation, rapid eye movement sleep (REM) to non rapid eye movement sleep (NREM) alterations and circadian changes often precede classic motor symptoms. Structural and functional hypothalamic changes have been observed in early ALS, suggesting a direct role in sleep-wake dysregulation. In addition, impaired glymphatic clearance during sleep may contribute to neurodegeneration by impairing the removal of protein waste. Polysomnographic studies and cohort data support the presence of prodromal sleep abnormalities in both symptomatic patients and gene mutation carriers. Noninvasive ventilation has shown benefits not only in respiratory management but also in improving sleep quality and overall prognosis.

SUMMARY: Sleep alterations in ALS are increasingly recognized as early indicators and potential modulators of disease progression. The hypothalamus and the glymphatic system emerge as key contributors to these disturbances, highlighting sleep as a therapeutic target. Understanding the role of sleep in ALS pathophysiology may aid in earlier diagnosis and novel intervention strategies aimed at modifying disease course.}, } @article {pmid40832332, year = {2025}, author = {Garrett, TL and Wintermute, L and Armitage, M and Ward, S and Halim, IA and Mousa, MH and Gerber, K and Elbasiouny, SM}, title = {Circular continuum of alpha motoneuron types.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2025.08.12.669858}, pmid = {40832332}, issn = {2692-8205}, abstract = {UNLABELLED: Alpha-motoneurons (α-MNs) are traditionally classified into slow (S), fast fatigue-resistant (FR), and fast-fatigable (FF), which exist along a continuum of properties between slow and fast, enabling the generation of graded force and seamless movement. Using combinations of markers, we developed novel immunohistochemistry protocols that enabled co-labeling of six major and transitional α-MN types throughout the mouse lumbar spinal cord with unprecedented detail. Intriguingly, our protocols labeled for the first time: α-MNs of the fast fatigue intermediate (FI) type; a previously undescribed transitional α-MN subtype (FR/FI); and a novel subtype of α-MNs exhibiting hybrid characteristics of both S and FF types - termed S/FF - which resist ALS degeneration. Electrophysiological recordings confirmed FR/FI and S/FF subtypes, both exhibiting mixed traits. The discovery of S/FF subtype reveals that α-MNs exist along a circular continuum between slow and fast types, challenging the traditional linear model and reshaping our understanding of their role in motor control.

SIGNIFICANCE STATEMENT: This work is significant in three major ways: Technical innovation : We introduce a novel immunohistochemistry protocol capable of co-labeling six distinct and transitional α-MN types in the adult spinal cord. This tool will be highly valuable for the broader neuroscience community. Conceptual breakthrough : The discovery of a circular rather than linear continuum of α-MN types represents a paradigm shift in our understanding of α-MN organization and their role in motor control. Relevance to disease : The distinct susceptibilities of α-MN subtypes to degeneration - particularly in aging and ALS - highlight the importance of this new framework in studying neurodegenerative diseases. Our protocol enables this research with new levels of precision and rigor. In summary, this study has broad implications for understanding motor control in both healthy and diseased states.}, } @article {pmid40832293, year = {2025}, author = {Inami, S and Jenny, BP and Akpoghiran, O and Gallagher, SI and Strich, AK and Tonoki, A and Trotti, D and Haeusler, AR and Koh, K}, title = {Increased neuronal activity restores circadian function in Drosophila models of C9orf72-ALS/FTD.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2025.08.07.669085}, pmid = {40832293}, issn = {2692-8205}, abstract = {UNLABELLED: Circadian rhythm disruptions are common across neurodegenerative diseases, but their link to amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) remains unclear. The C9orf72 hexanucleotide repeat expansion is the most prevalent genetic cause of ALS/FTD. Here, we used Drosophila models expressing toxic arginine-rich dipeptides (PR or GR) or GGGGCC hexanucleotide repeats to investigate circadian deficits in C9orf72-ALS/FTD. We found that circadian rhythmicity and period length were disrupted in a repeat number-, dosage-, and age-dependent manner. Additionally, we observed lower levels of the neuropeptide PDF, a key regulator of free-running circadian rhythms, as well as decreased projection complexity and reduced neuronal activity in PDF-expressing neurons. Importantly, increases in neuronal activity significantly restored circadian function under select conditions. These results implicate reduced neuronal activity in C9orf72-ALS/FTD circadian deficits, underscoring the importance of precisely tuned, circuit- and stage-specific interventions.

HIGHLIGHTS: C9orf72 dipeptide and nucleotide repeats disrupt circadian rhythms in Drosophila Circadian dysfunction with reduced PDF and neurites emerges before neuron lossIncreased neuronal activity rescues mild circadian dysfunctionActivity-based rescue is effective across ages and models when precisely tuned.}, } @article {pmid40832276, year = {2025}, author = {Ramani, B and Ehsani, K and Kampmann, M}, title = {The Hsp40 co-chaperone DNAJC7 modifies polyglutamine but not polyglycine aggregation.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2025.08.10.669490}, pmid = {40832276}, issn = {2692-8205}, abstract = {Polyglutamine (polyQ) diseases, including Huntington's disease and several spinocerebellar ataxias, are caused by abnormally expanded CAG nucleotide repeats, which encode aggregation-prone polyQ tracts. Substantial prior evidence supports a pathogenic role for polyQ protein misfolding and aggregation, with molecular chaperones showing promise in suppressing disease phenotypes in cellular and animal models. In this study, we developed a FRET-based reporter system that models polyQ aggregation in human cells and used it to perform a high-throughput CRISPR interference screen targeting all known molecular chaperones. This screen identified as a strong suppressor of polyQ aggregation the Hsp40 co-chaperone DNAJC7, which has previously been shown to modify aggregation of other disease proteins (tau and TDP-43) and has mutations causative for amyotrophic lateral sclerosis. We validated this phenotype and further established a physical interaction between DNAJC7 and polyQ-expanded protein. In contrast, DNAJC7 did not modify aggregation of polyglycine (polyG) in a FRET-based model of neuronal intranuclear inclusion disease. In addition to establishing new inducible, scalable cellular models for polyQ and polyG aggregation, this work expands the role of DNAJC7 in regulating folding of disease-associated proteins.}, } @article {pmid40832231, year = {2025}, author = {Jude, JJ and Haro, S and Levi-Aharoni, H and Hashimoto, H and Acosta, AJ and Card, NS and Wairagkar, M and Brandman, DM and Stavisky, SD and Williams, ZM and Cash, SS and Simeral, JD and Hochberg, LR and Rubin, DB}, title = {Decoding intended speech with an intracortical brain-computer interface in a person with longstanding anarthria and locked-in syndrome.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2025.08.12.668516}, pmid = {40832231}, issn = {2692-8205}, abstract = {Intracortical brain-computer interfaces (iBCIs) for decoding intended speech have provided individuals with ALS and severe dysarthria an intuitive method for high-throughput communication. These advances have been demonstrated in individuals who are still able to vocalize and move speech articulators. Here, we decoded intended speech from an individual with longstanding anarthria, locked-in syndrome, and ventilator dependence due to advanced symptoms of ALS. We found that phonemes, words, and higher-order language units could be decoded well above chance. While sentence decoding accuracy was below that of demonstrations in participants with dysarthria, we are able to attain an extensive characterization of the neural signals underlying speech in a person with locked-in syndrome and through our results identify several directions for future improvement. These include closed-loop speech imagery training and decoding linguistic (rather than phonemic) units from neural signals in middle precentral gyrus. Overall, these results demonstrate that speech decoding from motor cortex may be feasible in people with anarthria and ventilator dependence. For individuals with longstanding anarthria, a purely phoneme-based decoding approach may lack the accuracy necessary to support independent use as a primary means of communication; however, additional linguistic information embedded within neural signals may provide a route to augment the performance of speech decoders.}, } @article {pmid40831763, year = {2025}, author = {B S, P and Talwar, P}, title = {Influence of palmitoylation in axonal transport mechanisms in neurodegenerative diseases.}, journal = {Frontiers in cellular neuroscience}, volume = {19}, number = {}, pages = {1613379}, pmid = {40831763}, issn = {1662-5102}, abstract = {Progressive functional loss and death of neurons are characteristics of neurodegenerative diseases such as Alzheimer's disease (AD), Amyotrophic lateral sclerosis (ALS), and Parkinson's disease (PD). These diseases are often linked with disruptions in axonal transport and synaptic functions. Accumulation of misfolded proteins is observed as a commonly shared pathology for these diseases, where aberrant accumulation of amyloid beta (Aβ), tau, α-synuclein (α-syn) and TAR DNA-binding protein 43 (TDP-43), are found in AD, PD and ALS, respectively. These accumulations are observed to be involved in disrupting axonal transport and compromising neuronal survival. Axonal transport is an essential process where proper functioning of the transport mechanism is important for maintaining neuronal hemostasis by transporting of proteins, organelles and neurotransmitter complexes. This review explores the role of palmitoylation in regulating neuronal axonal transport and their impact on other neuronal functions along with neurodegeneration mechanisms. Palmitoylation is a reversible lipid modification, which is widely studied second to phosphorylation. Enzymes like palmitoyl acyltransferases and acyl-protein thioesterases are responsible for attachment and detachment of palmitic acid causing palmitoylation and depalmitoylation of neuronal proteins. In axonal transport, palmitoylation influences the localization and functioning of the proteins, which connectively plays a role in synaptic stability by interacting with synaptic scaffolding proteins and neurotransmission receptors.}, } @article {pmid40831234, year = {2025}, author = {Djordjevic, C}, title = {The Strange Afterlife of Logical Positivism: Nursing Research and Ghosts From the Past.}, journal = {Nursing philosophy : an international journal for healthcare professionals}, volume = {26}, number = {4}, pages = {e70036}, doi = {10.1111/nup.70036}, pmid = {40831234}, issn = {1466-769X}, mesh = {Humans ; *Nursing Research ; *Philosophy, Nursing ; *Logic ; *Nursing Theory ; }, abstract = {Corry, Porter, and McKenna recently argued that logical positivism is a dead 'research paradigm' and should be stricken from the textbooks. Though I wholeheartedly support moving beyond logical positivism, I think its demise has been greatly exaggerated. This essay traces the continued influence of logical positivism on the nursing discipline. It also examines how far-ranging the revisions would have to be if positivism is truly rejected from the nursing science. Section I argues that Corry et al.'s critique of positivism reiterates core positivist presuppositions. Sections II and III argue that positivist presuppositions about theories and operations still govern much nursing research. Section IV briefly discusses the role of values in the nursing science and argues that the positivists had an important point. This essay aims to clarify how deeply embedded positivism is in the nursing discipline, for it is only when we know how deep the infected tissue is that we can hope to excise it.}, } @article {pmid40830802, year = {2025}, author = {Tzeplaeff, L and Galhoz, A and Meijs, C and Caldi Gomes, L and Kovac, A and Menzel, A and Değirmenci, H and Alaamel, A and Kaya, HC and Çelik, AG and Dinçer, S and Korucuk, M and Karaüzüm, SB and Bayraktar, E and Çiftçi, V and Bilge, U and Koç, F and Demleitner, AF and Buchberger, A and von Heynitz, R and Gmeiner, V and Knellwolf, C and Mouzouri, M and Wuu, J and Başak, AN and Andersen, PM and Kohlmayer, F and Ashton, NJ and Kuban, W and Lenz, C and Rogers, ML and Zilka, N and Corcia, P and Lerner, Y and Weber, M and Turcanova Koprusakova, M and Uysal, H and Benatar, M and Menden, MP and Lingor, P}, title = {Identification of a presymptomatic and early disease signature for amyotrophic lateral sclerosis (ALS): protocol of the premodiALS study.}, journal = {Neurological research and practice}, volume = {7}, number = {1}, pages = {56}, pmid = {40830802}, issn = {2524-3489}, support = {01ED2204A//Bundesministerium für Bildung und Forschung/ ; 01ED2204A//Bundesministerium für Bildung und Forschung/ ; 01ED2204B//Bundesministerium für Bildung und Forschung/ ; 01ED2204B//Karlsruhe School of Elementary Particle and Astroparticle Physics: Science and Technology, Karlsruhe Institute of Technology/ ; EXC 2145//Germany's Excellence Strategy within the framework of the Munich Cluster for Systems Neurology/ ; SyNergy - ID 390857198//Germany's Excellence Strategy within the framework of the Munich Cluster for Systems Neurology/ ; No. 950293 - COMBAT-RES//European Union's Horizon 2020 Research and Innovation Programme/ ; 112N004//Scientific and Technological Research Council of Turkey (TÜBİTAK)/ ; 32ND30_206536//Swiss National Science Foundation (SNSF)/ ; ANR-21-JPW2-0007-03//Agence Nationale de la Recherche/ ; 2021/03/Y/NZ7/00111//Polish National Science Center (NCN)/ ; 3-18370//Ministry of Health of Israel/ ; 05-CIG-Rogers 2022//FightMND/ ; R01NS105479//U.S. National Institutes of Health/ ; R01NS105479//U.S. National Institutes of Health/ ; }, abstract = {INTRODUCTION: The median time to diagnosis of amyotrophic lateral sclerosis (ALS) is approximately 12 months after the onset of first symptoms. This diagnostic delay is primarily due to the nonspecific nature of early symptoms and the clinical challenges in differentiating ALS from its mimics. Therefore, the discovery of reliable biomarkers for the early and accurate diagnosis of ALS represents a critical medical need.

METHODS: A total of 330 participants will be recruited across six international study sites. The cohort will include (1) pre-symptomatic gene mutation carriers, (2) symptomatic individuals up to 12 months after symptom onset with either ALS, ALS mimics, or a pure motor syndrome with yet unclear assignment, and (3) healthy controls. Participants will engage in a one-year longitudinal study, consisting of an initial evaluation at baseline visit and a follow-up visit 12 months later. Assessments will include an environmental and medical history questionnaire, neurological examinations, olfactory testing, cognitive/behavioral evaluations, and the collection of biological samples (serum, plasma, urine, tear fluid, and cerebrospinal fluid). Proteomic, metabolomic, and lipidomic analyses will be performed using mass spectrometry and targeted immunoassays, with all samples processed under standardized protocols. The resulting multimodal dataset will be systematically integrated in an effort to uncover a presymptomatic and early ALS signature. Perspective The premodiALS study aim to identify a clinico-molecular signature characteristic of presymptomatic and early ALS. These findings may have relevance to early diagnosis and future clinical practice for ALS disease.}, } @article {pmid40657896, year = {2025}, author = {Dogra, SR and Bhonsle, J and Sharma, A}, title = {MicroRNA Dysregulation in Neurodegeneration: Role, Biomarker Potential and Therapeutics.}, journal = {The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques}, volume = {}, number = {}, pages = {1-12}, doi = {10.1017/cjn.2025.10361}, pmid = {40657896}, issn = {0317-1671}, abstract = {Neurodegenerative diseases (NDDs) are a group of complex disorders marked by pathophysiological mechanisms involving protein aggregation, mitochondrial dysfunction, oxidative stress and neuroinflammation. Irrespective of extensive research advances, NDDs have become a serious global concern and persist as a major therapeutic challenge. In recent years, microRNAs (miRNAs), a class of small non-coding RNAs, have established a pivotal role in combating NDDs. The altered expression of miRNAs is reported to be associated with the progression of various NDDs. This review aims to discuss miRNA biogenesis; dysregulation in NDDs, specifically Alzheimer's disease, Parkinson's disease (PD) and amyotrophic lateral sclerosis; their potential as biomarkers; and promising therapeutic targets. Additionally, there are various emerging technologies discussed that are advanced approaches to enhance miRNA-based diagnostics and therapeutics.}, } @article {pmid40830689, year = {2025}, author = {Rusecka, JM and Kierdaszuk, B and Stępniak, I and Rydzanicz, M and Stawiński, P and Gambin, T and Loska, D and Kacprzak, MM and Kaliszewska, M and Piekutowska-Abramczuk, D and Kamińska, AM and Pronicka, E and Bartnik, E and Kostera-Pruszczyk, A and Płoski, R and Sobczyńska-Tomaszewska, A and Tońska, K}, title = {Ataxia and oculomotor apraxia caused by a large-scale deletion in the senataxin gene.}, journal = {Journal of applied genetics}, volume = {}, number = {}, pages = {}, pmid = {40830689}, issn = {2190-3883}, support = {2014/15/B/NZ5/00434//Narodowe Centrum Nauki/ ; 2012/05/B/NZ2/01627//Narodowe Centrum Nauki/ ; 2013/09/N/NZ5/00836//Narodowe Centrum Nauki/ ; IP2015 019874//Ministerstwo Edukacji i Nauki/ ; VENTURES/2011-8/3//Fundacja na rzecz Nauki Polskiej/ ; }, abstract = {Senataxin, an RNA/DNA helicase, is a key protein providing genome stability and one of the best characterized R-loop-binding factors playing an important role in transcription and DNA repair processes. Pathogenic SETX gene variants cause autosomal recessive spinocerebellar ataxia with axonal neuropathy (AOA2, MIM #606002) and autosomal dominant juvenile amyotrophic lateral sclerosis (ALS4, MIM #602433), rare neurodegenerative disorders characterized by juvenile onset of progressive cerebellar ataxia, axonal sensorimotor peripheral neuropathy, combined upper and lower motor neuron symptoms, and increased serum alpha-fetoprotein (AFP; specific for AOA2). We report two cases of adult patients presenting with cerebellar syndrome, scanned speech, and exercise intolerance which started in the second/third decade of life and were followed by muscle weakness and impaired gait coordination. Whole exome sequencing (WES) was performed to analyze single nucleotide and copy number variants. A decreased coverage of a genomic region of around 16 kb on chromosome 9 (chr9:132,295,852-132,311,876), suggesting a deletion encompassing 5 exons of the SETX gene (exons 11-15, NM_015046.7) was observed. This homozygous SETX (9q34.13) deletion leads to a frame shift and consequently truncation of the helicase domain in the protein. Loss-of-function variants in the SETX gene are known to be pathogenic. Statistical analysis of NGS data from the Polish population identified a few heterozygous carriers, suggesting its region-specific origin.}, } @article {pmid40830661, year = {2025}, author = {Chia, R and Moaddel, R and Kwan, JY and Rasheed, M and Ruffo, P and Landeck, N and Reho, P and Vasta, R and Calvo, A and Moglia, C and Canosa, A and Manera, U and Snyder, A and Saez-Atienzar, S and Grassano, M and Brunetti, M and Casale, F and Ray, A and Arvind, K and Comertpay, B and Zhu, M and Gibbs, JR and , and Alba, C and Dawson, TM and Rosenthal, LS and Hall, AJ and Pantelyat, AY and Narendra, DP and Ehrlich, DJ and Walker, KA and Kosa, P and Bielekova, B and Egan, JM and Candia, J and Tanaka, T and Ferrucci, L and Dalgard, CL and Scholz, SW and Chiò, A and Traynor, BJ}, title = {A plasma proteomics-based candidate biomarker panel predictive of amyotrophic lateral sclerosis.}, journal = {Nature medicine}, volume = {}, number = {}, pages = {}, pmid = {40830661}, issn = {1546-170X}, support = {1ZIAAG000933//U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ ; }, abstract = {Identifying a reliable biomarker for amyotrophic lateral sclerosis (ALS) is crucial for clinical practice. Here, in this cross-sectional study, we used the Olink Explore 3072 platform to investigate plasma proteomics as a biomarker tool for this neurodegenerative condition. Thirty-three proteins were differentially abundant in the plasma of patients with ALS (n = 183) versus controls (n = 309). We replicated our findings in an independent cohort (n = 48 patients with ALS and n = 75 controls). We then applied machine learning to create a model that diagnosed ALS with high accuracy (area under the curve, 98.3%). By analyzing plasma samples from individuals before ALS symptoms emerged, we estimated the age of clinical onset and showed that the disease process-impacting skeletal muscle, nerves and energy metabolism-occurs years before symptoms appear. Our research suggests that plasma proteins can be a biomarker for this fatal disease and offers molecular insights into its prodromal phase.}, } @article {pmid40830488, year = {2025}, author = {Schippers, A and Vansteensel, MJ and Freudenburg, ZV and Luo, S and Crone, NE and Ramsey, NF}, title = {Don't put words in my mouth: speech perception can falsely activate a brain-computer interface.}, journal = {Journal of neuroengineering and rehabilitation}, volume = {22}, number = {1}, pages = {181}, pmid = {40830488}, issn = {1743-0003}, support = {SGW-406-18-GO-086//Nederlandse Organisatie voor Wetenschappelijk Onderzoek/ ; SGW-406-18-GO-086//Nederlandse Organisatie voor Wetenschappelijk Onderzoek/ ; SGW-406-18-GO-086//Nederlandse Organisatie voor Wetenschappelijk Onderzoek/ ; SGW-406-18-GO-086//Nederlandse Organisatie voor Wetenschappelijk Onderzoek/ ; UGT7685//Stichting voor de Technische Wetenschappen/ ; UGT7685//Stichting voor de Technische Wetenschappen/ ; UGT7685//Stichting voor de Technische Wetenschappen/ ; UGT7685//Stichting voor de Technische Wetenschappen/ ; ERC-Advanced 'iConnect' project, grant ADV 320708/ERC_/European Research Council/International ; ERC-Advanced 'iConnect' project, grant ADV 320708/ERC_/European Research Council/International ; ERC-Advanced 'iConnect' project, grant ADV 320708/ERC_/European Research Council/International ; ERC-Advanced 'iConnect' project, grant ADV 320708/ERC_/European Research Council/International ; U01DC016686/DC/NIDCD NIH HHS/United States ; U01DC016686/DC/NIDCD NIH HHS/United States ; U01DC016686/DC/NIDCD NIH HHS/United States ; U01DC016686/DC/NIDCD NIH HHS/United States ; U01DC016686/DC/NIDCD NIH HHS/United States ; U01DC016686/DC/NIDCD NIH HHS/United States ; UH3NS114439/NS/NINDS NIH HHS/United States ; UH3NS114439/NS/NINDS NIH HHS/United States ; UH3NS114439/NS/NINDS NIH HHS/United States ; UH3NS114439/NS/NINDS NIH HHS/United States ; UH3NS114439/NS/NINDS NIH HHS/United States ; UH3NS114439/NS/NINDS NIH HHS/United States ; PPS-2021-02//Dutch Brain Foundation/ ; PPS-2021-02//Dutch Brain Foundation/ ; 101070939//HORIZON EUROPE European Innovation Council/ ; 101070939//HORIZON EUROPE European Innovation Council/ ; }, mesh = {Humans ; *Brain-Computer Interfaces ; *Speech Perception/physiology ; Male ; Adult ; Electrocorticography ; Female ; Speech/physiology ; *Sensorimotor Cortex/physiology ; Support Vector Machine ; }, abstract = {BACKGROUND: Recent studies have demonstrated that speech can be decoded from brain activity which in turn can be used for brain-computer interface (BCI)-based communication. It is however also known that the area often used as a signal source for speech decoding BCIs, the sensorimotor cortex (SMC), is also engaged when people perceive speech, thus making speech perception a potential source of false positive activation of the BCI. The current study investigated if and how speech perception may interfere with reliable speech BCI control.

METHODS: We recorded high-density electrocorticography (HD-ECoG) data from five subjects while they performed a speech perception and a speech production task. We first evaluated whether speech perception and production activated the SMC. Second, we trained a support-vector machine (SVM) on the speech production data (including rest). To test the occurrence of false positives, this decoder was then tested on speech perception data where every perception segment that was classified as a produced syllable rather than rest was considered a false positive. Finally, we investigated whether perceived speech could be distinguished from produced speech and rest.

RESULTS: Our results show that both the perception and production of speech activate the SMC. In addition, we found that decoders that are highly reliable at detecting self-produced syllables from brain signals may generate false positive BCI activations during the perception of speech and that it is possible to distinguish perceived speech from produced speech and rest, with high accuracy.

CONCLUSIONS: We conclude that speech perception can interfere with reliable BCI control, and that efforts to limit the occurrence of false positives during daily-life BCI use should be implemented in BCI design to increase the likelihood of successful adoptation by end users.}, } @article {pmid40829936, year = {2025}, author = {Dey, S and Quintanilla, C and Bitlis, D and Gautam, M and Ozdinler, PH and Martina, M}, title = {Cell type-specific alterations in excitability and inhibition of upper motor neurons in AlsinKO mice, a model of juvenile onset ALS.}, journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, volume = {}, number = {}, pages = {}, doi = {10.1523/JNEUROSCI.2409-24.2025}, pmid = {40829936}, issn = {1529-2401}, abstract = {In amyotrophic lateral sclerosis (ALS) motor cortex hyperexcitability is detected in both familial and sporadic cases, suggesting its centrality in the ALS phenotype; the underlying mechanisms, however, remain largely obscure. Here we utilize male and female UCHL1-eGFP (UeGFP) mice, in which the corticospinal neurons of the motor cortex are labeled with green fluorescent protein, to investigate the intrinsic excitability and synaptic inhibitory inputs on distinct neuron populations in WT-UeGFP and presymptomatic AlsinKO-UeGFP mice, which lack Alsin function and are a well-characterized mouse model for juvenile cases of ALS. We show that in the motor cortex of AlsinKO-UeGFP mice, eGFP-positive layer 5 pyramidal neurons, which represent upper motor neurons, show a decrease in intrinsic excitability compared with WT, whereas the electrophysiological properties of eGFP-negative cells, which identify callosal projection neurons, are unaffected. This alteration in intrinsic excitability, however, is counterbalanced by a decrease in the frequency of spontaneous inhibitory currents due to a cell-specific reduction in the number of inhibitory synaptic contacts on upper motor neurons. Thus, the overall excitability of upper motor neurons only displays negligible changes despite large alterations in intrinsic excitability and inhibitory synaptic input, which may explain why mice do not exhibit a prominent motor phenotype. The presence of this homeostatic interaction between intrinsic excitability and synaptic inhibition raises the question of which of the two changes is primary, and which is secondary, and shows that decreased function of motor cortex interneurons is an early event in ALS with Alsin mutations.Significance Statement We found that in AlsinKO mice, which recapitulate ALS disease in patients with Alsin mutations, intrinsic excitability and inhibitory synaptic input of upper motoneurons (but not callosal-projection neurons) are significantly reduced at presymptomatic disease stage. We show that in this model: 1) impaired function of cortical interneurons is an early event; 2) excitability alteration in the motor cortex is cell type-specific; 3) intrinsic excitability and synaptic inhibition are linked by a homeostatic mechanism. These results stress the importance of cortical interneurons in ALS and suggest that either homeostatic overcompensation or failure of compensation contribute to disease onset and progression. If these mechanisms are common in ALS patients, this may have important consequences for the design of novel therapeutic interventions.}, } @article {pmid40829878, year = {2025}, author = {Malaspina, A}, title = {Moving past NfL? Multibiomarker models for ALS prognosis and stratification.}, journal = {Journal of neurology, neurosurgery, and psychiatry}, volume = {}, number = {}, pages = {}, doi = {10.1136/jnnp-2025-336814}, pmid = {40829878}, issn = {1468-330X}, } @article {pmid40829685, year = {2025}, author = {Wang, Y and Zhou, Y and Tian, H and Li, Q and Chen, Y and Wang, L and Yin, Z and Zhou, J and Liang, F}, title = {NF-κB signalling pathway in neurodegenerative diseases: Acupuncture as a potential therapeutic approach.}, journal = {Brain research}, volume = {}, number = {}, pages = {149893}, doi = {10.1016/j.brainres.2025.149893}, pmid = {40829685}, issn = {1872-6240}, abstract = {The NF-κB signaling pathway plays a crucial role in the pathogenesis of neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis, particularly through its role in the regulation neuroinflammation, oxidative stress, protein misfolding, and apoptosis. Emerging evidence suggests that acupuncture modulates the NF-κB pathway, thus offering therapeutic potential by mitigating neuroinflammation, reducing oxidative stress, and protecting mitochondrial function. Specifically, acupuncture inhibits NF-κB activation, downregulates pro-inflammatory mediators like TNF-α and IL-6, and mitigates neurotoxicity and apoptosis. These effects are substantiated in animal models of Alzheimer's and Parkinson's diseases, with preliminary evidence in amyotrophic lateral sclerosis models. However, current studies largely rely on preclinical models with limited acupoint selection, short observation periods, and a lack of standardized protocols, posing challenges for translation to clinical settings. Future research should prioritize well-designed clinical trials, expand acupoint combinations, and explore synergistic effects with conventional therapies, aiming to maximize acupuncture's therapeutic efficacy in neurodegenerative diseases.}, } @article {pmid40828747, year = {2025}, author = {Vijayaraghavan, A and Nair, SS and Poyuran, R and Sukumaran, S and Sundaram, S}, title = {Neuroimmunological Crossroads: A Rare Co-occurrence of Myasthenia Gravis and IgLON-related Amyotrophic Lateral Sclerosis.}, journal = {Neurology India}, volume = {}, number = {}, pages = {}, doi = {10.4103/neurol-india.Neurol-India-D-25-00148}, pmid = {40828747}, issn = {1998-4022}, } @article {pmid40828270, year = {2025}, author = {Harerimana, A and Pillay, JD and Mchunu, G}, title = {The pitfalls of "toughing it out": mapping stoic attitudes in cancer patients. A scoping review.}, journal = {Medicine, health care, and philosophy}, volume = {}, number = {}, pages = {}, pmid = {40828270}, issn = {1572-8633}, abstract = {Stoicism (with an upper-case 'S') as a life philosophy promotes resilience, self-control and rational acceptance of adversity. In contrast, lower-case stoicism, including pseudo-stoicism or stoic attitudes-characterised by emotional suppression and the silent endurance of pain or hardship-has been linked to adverse health outcomes among cancer patients. Thus, further research is needed to understand the drawbacks of stoic attitudes in cancer patients. This scoping review aims to map stoic attitudes in cancer patients, particularly in relation to potential health consequences. The review adhered to Levac et al.'s framework for scoping reviews. A systematic search was conducted from five electronic databases: CINAHL, Emcare, Medline Ovid, Scopus, and Web of Science. Manual searches were conducted using Google and Google Scholar. A total of 955 records were identified, 526 were screened (title and abstracts), and 450 were excluded. After reviewing 76 full-text articles, 12 studies satisfied the inclusion criteria for data extraction and thematic analysis, consisting of five qualitative and seven quantitative studies. A time frame of 10 years was considered, ranging from 2014 to 2024. This scoping review revealed that pseudo-stoic attitudes in cancer patients often lead to emotional suppression, reduced social support, delayed help-seeking and poor management of symptoms such as pain. These attitudes were linked to poorer psychological outcomes and underreporting of symptoms, especially among older males and rural cancer patients. Studies found that stoic traits were sometimes associated with persistence and treatment adherence among cancer patients. Pseudo-stoicism hinders emotional expression and delays help-seeking, leading to adverse health outcomes; however, stoic attitudes are also associated with adaptive qualities, such as psychological endurance and a commitment to care. Therefore, it is vital to promote balanced coping strategies that honour resilience while encouraging open emotional engagement among cancer patients.}, } @article {pmid40827427, year = {2025}, author = {Mehta, AK and Kojimoto, G and O'Riordan, DL and Leavell, YL and Maiser, S and Grouls, A and Smith, AK and Pantilat, SZ and Kluger, BM and Bischoff, KE}, title = {Patients' and Caregivers' Perceptions of Specialty Palliative Care for Amyotrophic Lateral Sclerosis: A Multicenter Evaluation.}, journal = {Muscle & nerve}, volume = {}, number = {}, pages = {}, doi = {10.1002/mus.70006}, pmid = {40827427}, issn = {1097-4598}, support = {A142921//ALS Association/ ; }, abstract = {INTRODUCTION/AIMS: Specialty palliative care (SPC) aims to optimize quality of life for people with life-limiting illnesses. Previous studies support benefits of SPC for people with amyotrophic lateral sclerosis (pALS) and their caregivers; however, few studies have compared patient and caregiver experiences with ALS care and SPC.

METHODS: An online survey assessing satisfaction with care was distributed to pALS and caregivers who had received SPC. Those who completed the survey were also invited to participate in a semi-structured interview.

RESULTS: Thirty-four people (10 pALS, 25 caregivers) from 26 ALS clinics in 20 states completed the survey. Sixteen also provided a qualitative interview. Respondents were most commonly satisfied with their ALS team's ability to answer questions (81%), counsel them regarding ALS medications (78%), and manage motor symptoms (77%). Respondents were least commonly satisfied with their ALS team's ability to manage mood (50%), address spiritual/existential concerns (48%), and help them find in-home care providers (38%). SPC was initiated an average of 14.6 months after ALS diagnosis. Respondents were most commonly satisfied with their SPC team's responsiveness to time-sensitive needs between scheduled visits (82%) and management of mood (80%) and non-pain physical symptoms (73%). Respondents were least commonly satisfied with their SPC team's ability to help with equipment needs (52%), make decisions about procedures (50%), and find in-home caregivers (46%). Interviews highlighted the emotional support and care coordination that SPC teams provide.

DISCUSSION: pALS and caregivers identified distinct and complementary strengths of ALS and SPC teams, suggesting that collaboration between teams may provide the most comprehensive care.}, } @article {pmid40826812, year = {2025}, author = {Asano, H and Kawaguchi, T and Kato, C and Morimoto, S and Yano, M and Minaguchi, M and Yasuda, D and Fukushima, K and Okano, H}, title = {Ropinirole Functions Through a Dopamine Receptor D2-Independent Mechanism to Ameliorate Amyotrophic Lateral Sclerosis Phenotypes in TARDBP-Mutant iPSC-Derived Motor Neurons.}, journal = {Journal of neurochemistry}, volume = {169}, number = {8}, pages = {e70183}, doi = {10.1111/jnc.70183}, pmid = {40826812}, issn = {1471-4159}, support = {JP21H05278//Japan Society for the Promotion of Science/ ; JP22K15736//Japan Society for the Promotion of Science/ ; JP20H00485//Japan Agency for Medical Research and Development/ ; JP21wm0425009//Japan Agency for Medical Research and Development/ ; JP22bm0804003//Japan Agency for Medical Research and Development/ ; JP22ek0109616//Japan Agency for Medical Research and Development/ ; JP23bm1123046//Japan Agency for Medical Research and Development/ ; JP23bm1423002//Japan Agency for Medical Research and Development/ ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by motor neuron (MN) degeneration. Ropinirole hydrochloride (ROPI), a dopamine receptor D2 (DRD2) agonist, was identified through phenotypic screening of MNs derived from patient-derived induced pluripotent stem cells (iPSCs) as a disease model and has emerged as a promising candidate drug for ALS treatment. The ROPALS trial, a phase I/IIa trial in patients with ALS, suggested the safety and efficacy of ROPI, albeit in a small sample size. Interestingly, a DRD2 antagonist and modulator only partially mitigated the suppressive effect of ROPI on the ALS phenotype, and the detailed mechanism of ROPI activity remains unclear. Therefore, in this study, we investigated whether the therapeutic effects of ROPI in ALS are dependent on DRD2. For this purpose, we generated DRD2-deficient iPSCs and showed that ROPI effectively reduced neuronal cell death, reactive oxygen species (ROS) production, and neuronal hyperexcitation, independently of DRD2. Further analyses revealed that ROPI corrected aberrant RNA splicing and restored the mRNA expression of mitochondrial proteins in a DRD2-independent manner. Our findings suggest that ROPI not only functions as a canonical DRD2 agonist but also has pleiotropic DRD2-independent effects, offering a novel avenue for treatment strategies that target multiple pathways involved in ALS pathology.}, } @article {pmid40826370, year = {2025}, author = {Feneberg, E and Thompson, AG and Charles, PD and Vendrell, I and Kessler, BM and Fischer, R and Ansorge, O and Gray, E and Talbot, K and Turner, MR}, title = {TDP-43 pathology is associated with divergent protein profiles in ALS brain and spinal cord.}, journal = {Acta neuropathologica communications}, volume = {13}, number = {1}, pages = {175}, pmid = {40826370}, issn = {2051-5960}, support = {ARUK AVR01961//Alzheimer's Research UK small grant/ ; Clinical Post Doctoral Fellowship//Guarantors of Brain/ ; }, abstract = {Neuronal and glial cytoplasmic inclusions positive for TAR DNA-binding protein 43 (TDP-43) are the defining pathological hallmark of 97% of amyotrophic lateral sclerosis (ALS) and 50% of frontotemporal dementia (FTD). The ALS-FTD clinicopathological spectrum variably involves cortical and spinal anterior horn cell pathology. The broader protein composition of these inclusions is of major importance to understanding pathogenesis, clinical heterogeneity and biomarker development. This study examined the proteome associated with TDP-43 inclusions in ALS, using mass spectrometry-based proteomic analysis of spinal cord and cerebral cortex from donors with phosphoTDP-43 positive ALS (n = 16), alpha-synuclein positive Parkinson's disease (PD, n = 8), phosphotau and beta-amyloid positive Alzheimer's disease (AD, n = 8) and age matched non-neurological controls (n = 8), comparing ALS with non-ALS conditions, spinal cord with cerebral cortex samples, and detergent-soluble with -insoluble fractions. Increased abundance of TDP-43 in the detergent-insoluble fraction of ALS cortex and spinal cord tissue confirmed disease-specific protein enrichment by serial fractionation. The most striking alterations between ALS and other conditions were found in the detergent-insoluble fraction of spinal cord, with predominant enrichment of endosomal and extracellular vesicle pathways. In the cortex mitochondrial membrane/envelope and ion transmembrane transport pathways were enriched in the detergent-insoluble fraction. RNA/DNA metabolic processes (in spinal cord) versus mitochondrial and synaptic protein pathways (in cortex) were upregulated in the detergent-soluble fraction of ALS cases and downregulated in the insoluble protein fraction. Whilst motor cortex and spinal cord may not optimally reflect disease-specific pathways in AD, in PD a significant enrichment of alpha-synuclein in the detergent-insoluble fraction of spinal cord was found. Among proteins concordantly elevated in the detergent-insoluble fractions of spinal cord and cortex, there was greater representation of proteins encoded by ALS-associated genes, specifically Cu/Zn superoxide dismutase 1, valosin containing protein and TDP-43 (odds ratio 16.34, p = 0.002). No significant increase in TDP-43 interacting proteins was observed in either detergent-soluble or -insoluble fractions. Together, this study shows a divergence in the composition of proteins associated with TDP-43 positive detergent-insoluble inclusions between spinal cord and cerebral cortex. A common upregulation of proteins encoded by ALS-causing genes implicates their role in the pathogenesis of the ALS-FTD spectrum of diseases beyond TDP-43. Data are available via ProteomeXchange with identifier PXD067060.}, } @article {pmid40825784, year = {2025}, author = {Flores, BN and Yu, SB and Cohen, IV and Fanok, MH and Luan, W and Maciuca, RD and Sun, LD and Tsai, RM and Vissers, M and Smits, L and Bunte, TM and Bakardjiev, A and Balasundar, S and Calvert, MEK and Chin, MY and Dobbins, SK and Dowdle, WE and Fang, M and Heuberger, JAAC and Ha, CL and Huang, F and Miyamoto, T and Osipov, M and Madrid San Martin, L and Saund, K and Tatarakis, D and Vu, AQ and Xiong, C and Yeo, GW and Groeneveld, GJ and van den Berg, LH and Dhuria, S and Estrada, AA and Jennings, D and Sandmann, T and Ho, C and Scearce-Levie, K and Yulyaningsih, E and Walker, AK and Di Paolo, G and Kane, LA and Troyer, MD and Lewcock, JW}, title = {Investigational eIF2B activator DNL343 modulates the integrated stress response in preclinical models of TDP-43 pathology and individuals with ALS in a randomized clinical trial.}, journal = {Nature communications}, volume = {16}, number = {1}, pages = {7690}, pmid = {40825784}, issn = {2041-1723}, abstract = {Neuronal TDP-43 aggregates are a hallmark ALS pathology. The integrated stress response (ISR) occurs downstream of TDP-43 pathology and may promote neurodegeneration. Here we demonstrate that a CNS penetrant small molecule eIF2B activator inhibits the ISR in cellular models of ALS and the brain of an inducible mouse model of TDP-43 pathology, where it transiently slowed progression of locomotor deficits and neurodegeneration. ISR activation was observed in ALS patient spinal cord and CSF. The investigational drug DNL343 was advanced into Phase 1 and Phase 1b randomized, double-blind, placebo-controlled trials in healthy and ALS participants, respectively (NCT04268784/NCT05006352); the primary objective in both studies was to investigate the safety and tolerability DNL343. DNL343 demonstrated a half-life supporting once-daily dosing and showed extensive CSF distribution. DNL343 was generally well tolerated and reduced ISR biomarkers in peripheral blood mononuclear cells and CSF of ALS participants. Therefore, DNL343 is a useful investigational drug to explore the effects of ISR inhibition in ALS models and individuals with neurological diseases.}, } @article {pmid40825663, year = {2025}, author = {Zhang, L and Pang, XW and Zhang, LY and Zhu, LF and Li, WN and Chu, YH and Zhou, LQ and Tian, DS and Qin, C and Chen, L}, title = {Gut microbiota and white matter integrity: a two-sample Mendelian randomization analysis.}, journal = {eNeuro}, volume = {}, number = {}, pages = {}, doi = {10.1523/ENEURO.0586-24.2025}, pmid = {40825663}, issn = {2373-2822}, abstract = {The causal relationship between gut microbiota (GM) and white matter injury and communication remains unclear. We aimed to scrutinize the plausible causal impact of GM on white matter hyperintensities (WMH), white matter microstructure, white matter connectivity and multiple neurological diseases via Mendelian randomization (MR) study. We identified 4 WMH-related bacterial taxa, including class Melainabacteria, order Gastranaerophilales, family Alcaligenaceae and genus Ruminiclostridium 6 In addition, 3 bacterial taxa were discovered that have consistent effect on multiple aspects of white matter microstructure. Furthermore, we found 12 strong associations between genetic liability in GM and white matter connectivity. Among these bacterial taxa, family Clostridiaceae 1 demonstrated a protective effect against ischemic stroke (IS). Genus Barnesiella showed protective effect on IS and small vessel stroke (SVS) while posed a risk effect on neuromyelitis optica spectrum disorder (NMOSD), as well as on aquaporin-4 immunoglobulin G-positive neuromyelitis optica spectrum disorder (AQP4-IgG + NMOSD). Order Desulfovibrionales and family Desulfovibrionaceae showed protective effect against cardioembolic stroke (CES) and genus Ruminococcus gnavus group showed a protective effect on amyotrophic lateral sclerosis (ALS). In terms of the mapped genes of statistically significant bacterial taxa, genes such as CPNE1, PIGU, MED22, SURF6, DOCK10, COPS3 exhibited a significant causal correlation with the corresponding white matter connectivity. This study demonstrated a genetically predicted causal relationship between GM and WMH, white matter microstructure, white matter connectivity, multiple neurological diseases, based on GWAS data from mixed-sex cohorts without sex-stratified summary statistics. These findings highlight the potential role of GM in influencing brain structural integrity.Significance Statement This is the first Mendelian randomization (MR) study to establish a relationship between the gut microbiota (GM) and brain white matter, identifying specific bacterial taxa with genetic responsibility for causal relationships with brain white matter. Our results indicate that 17 bacterial taxa associated with several white matter integrity and communication-related indexes. The MR study also identifies potential effects of GM in multiple neurological diseases, especially family Clostridiaceae 1, order Desulfovibrionales and family DesulfovibrionaceaeThis is the first study to utilize MR analysis in combination with Functional Mapping and Annotation analysis to explore the causal relationship between GM and brain white matter. Genes such as CPNE1, PIGU, MED22, SURF6, DOCK10, COPS3 exhibit a significant causal correlation with white matter connectivity.}, } @article {pmid40824756, year = {2025}, author = {García-Casanova, PH and Gascón-Giménez, F and Castillo-Villalba, J and Benatar, M and Vázquez-Costa, JF}, title = {Neurofilament light chain dynamics in the pre-symptomatic phase of amyotrophic lateral sclerosis: a case report.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {}, number = {}, pages = {1-5}, doi = {10.1080/21678421.2025.2542918}, pmid = {40824756}, issn = {2167-9223}, abstract = {This case report aims to describe the presymptomatic and prodromal phases of the disease in a sporadic patient with amyotrophic lateral sclerosis (ALS). A 41-year-old woman presented with acute hypesthesia due to transverse myelitis, with normal serum NfL levels. After six months, an increase in serum NfL, without clinical correlate, was found. One year after the myelitis, while serum NfL continued to increase, she experienced mild motor symptoms in the right hand, without definite signs of ALS. Disease progression over the following months finally lead to an ALS diagnosis, just as the NfL reached its peak. The emergence of both mild motor impairment as a prodromal stage of disease, and the sustained increase in NfL presymptomatically in a patient with sporadic ALS, highlights the expected similarities between genetic and non-genetic forms of disease. This case suggests the utility of NfL as a risk/susceptibility biomarker for predicting phenoconversion also in sporadic ALS patients.}, } @article {pmid40824693, year = {2025}, author = {Voronov, D and Park, S and Huang, L and Islegen-Wojdyla, A and Gullikson, E and Padmore, H and Wang, T and Idir, M}, title = {Fabrication and characterization of a full-size ultra-precise lamellar grating for the Cosmic beamline at ALS-U.}, journal = {Journal of synchrotron radiation}, volume = {}, number = {}, pages = {}, doi = {10.1107/S1600577525005946}, pmid = {40824693}, issn = {1600-5775}, support = {DE-AC02-05CH11231//US Department of Energy, Office of Science/ ; DE-SC0012704//US Department of Energy, Office of Science/ ; BNL LDRD 17-016//US Department of Energy, Office of Science/ ; FWP-PS032//US Department of Energy, Office of Science/ ; }, abstract = {We have developed a new process for the production of ultra-precise variable line spacing (VLS) lamellar diffraction gratings through nanofabrication. The process enables the fabrication of full-size X-ray gratings with sub-nanometre accuracy in groove depth, an optimal land-to-groove ratio, and uniform groove depth across the entire grating area. We also established a method for evaluating VLS groove density variation using stitched Fizeau interferometry. The measurements confirmed the exceptionally high accuracy of the VLS groove density in the fabricated gratings, which is well within the specification tolerances while the residual groove density errors are vanishingly small. The gold-coated grating demonstrated near-theoretical diffraction efficiency across the energy range of 100-1200 eV.}, } @article {pmid40823399, year = {2025}, author = {Soufi Amlashi, R and Forstmeier, S}, title = {The relationship of acculturative stress with meaning in life through the mediating role of difficulties in emotion regulation and meaning-centered coping style among international students in Germany.}, journal = {Frontiers in psychology}, volume = {16}, number = {}, pages = {1639194}, pmid = {40823399}, issn = {1664-1078}, abstract = {INTRODUCTION: With the increasing trend of international academic mobility, understanding the psychological outcomes of cultural transition has become crucial. The present study aimed to examine the relationship between acculturative stress and meaning in life (MIL), focusing on the mediating roles of difficulties in emotion regulation (DIER) and meaning-centered coping style (MCCS) among international students in Germany.

METHODS: This descriptive-correlational study recruited 443 students enrolled at German universities in 2024 through convenience sampling. Participants completed Sandhu & Asrabadi's Acculturative Stress Scale for International Students, Gratz & Roemer's DIER Scale, Eisenbeck et al.'s Meaning-Centered Coping Scale, and Steger et al.'s Meaning in Life Questionnaire. Data were analyzed using Pearson's correlation coefficient and structural equation modeling (SEM) in SPSS-26 and LISREL-10.20.

RESULTS: The findings indicated that acculturative stress was directly and positively associated with the search for meaning, and indirectly associated with both the presence of meaning and the search for meaning through DIER and MCCS. Specifically, acculturative stress was positively related to DIER, which in turn was negatively associated with the presence of meaning and positively with the search for meaning. Additionally, acculturative stress was negatively related to MCCS, which was positively linked to the presence of meaning, but not significantly to the search for meaning.

DISCUSSION: These results underscore the significance of emotional regulation and MCCS in mitigating the psychological effects of acculturative stress and promoting psychological wellbeing among international students.}, } @article {pmid40821767, year = {2025}, author = {Zhao, S and Fu, D and Lin, Y and Sun, X and Wang, X and Wu, X and Zhang, X}, title = {The role of the microbiome on immune homeostasis of the host nervous system.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1609960}, pmid = {40821767}, issn = {1664-3224}, abstract = {The gut microbiota is often termed the "second genome" of the human body. It has been shown to be one of the most significant environmental factors (non-genetic) influencing the onset, progression, and prognosis of various neurological and psychiatric disorders through its interactions with the host immune, nervous, and endocrine systems. Changes in the function and composition of the gut microbiota are strongly associated with amyotrophic lateral sclerosis, autism spectrum disorder, depression, Parkinson's disease, and Alzheimer's disease. This review summarizes the research regarding the associations and regulatory mechanisms between the gut microbiota and the central nervous system in order to explore the role of the gut microbiota in maintaining neural homeostasis.}, } @article {pmid40819701, year = {2025}, author = {Haslam, AX and Blandón, MDMT and Castro, ASR}, title = {Ocular manifestations in Dengue Fever: A Systematic Review and Meta-Analysis.}, journal = {American journal of ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ajo.2025.08.021}, pmid = {40819701}, issn = {1879-1891}, abstract = {TOPIC: Ocular manifestations in dengue fever remain underrecognized despite reports of vision-threatening complications. This systematic review and meta-analysis aimed to determine the pooled prevalence of ocular manifestations in dengue patients, characterizing their spectrum, frequency, and clinical significance.

CLINICAL RELEVANCE: Dengue fever affects millions globally, predominantly in tropical regions. While systemic complications are well documented, ophthalmic involvement remains poorly defined, with variable prevalence estimates and unclear risk factors. Early recognition is crucial for timely intervention, particularly in endemic areas where clinical suspicion is low.

METHODS: A comprehensive search was conducted in PubMed, CINAHL, and LILACS. Eligible studies included observational studies reporting the prevalence of ocular manifestations in dengue patients. Risk of bias was assessed using Hoy et al.'s tool for prevalence studies. Pooled prevalence estimates were calculated using a random-effects model, and heterogeneity was assessed using I[2] statistics.

RESULTS: A total of 32 studies, including 11,426 patients, were included. The pooled prevalence of ocular manifestations, calculated from 16 studies, was 0.32 (95% CI: 0.22-0.45, I[2] = 91.8%). Retro-ocular pain had a pooled prevalence of 0.20 (95% CI: 0.10-0.37, I[2] = 99.6%), while blurred vision was reported in 0.11 (95% CI: 0.05-0.23, I[2] = 92.8%). Among structural manifestations, subconjunctival hemorrhage had a prevalence of 0.18 (95% CI: 0.10-0.30, I[2] = 94.1%), retinal hemorrhage 0.08 (95% CI: 0.05-0.12, I[2] = 77.8%), maculopathy 0.04 (95% CI: 0.02-0.08, I[2] = 91.6%), and uveitis 0.05 (95% CI: 0.01-0.24, I[2] = 97.4%). Significant heterogeneity was observed across studies, likely due to differences in diagnostic criteria, study populations, and disease severity.

CONCLUSION: This study highlights a substantial prevalence of ocular manifestations in dengue patients, emphasizing the need for increased clinical awareness, particularly in endemic regions. Given the heterogeneity in reported prevalence, future research should focus on prospective, standardized ophthalmologic assessments to improve early diagnosis and management.}, } @article {pmid40819305, year = {2025}, author = {Guarnaccia, M and La Cognata, V and Gentile, G and Morello, G and Cavallaro, S}, title = {Unraveling the missing heritability of amyotrophic lateral sclerosis: should we focus more on copy number variations?.}, journal = {Neural regeneration research}, volume = {}, number = {}, pages = {}, doi = {10.4103/NRR.NRR-D-24-01604}, pmid = {40819305}, issn = {1673-5374}, } @article {pmid40819293, year = {2025}, author = {Abdurakhimova, D and Choi, S and Macheel, JM and Bednarchuk, HC and Lim, W}, title = {6-Minute Walk Test reference equation for individuals with Class III obesity in the U.S.: a comparison with an Italian cohort.}, journal = {Disability and rehabilitation}, volume = {}, number = {}, pages = {1-9}, doi = {10.1080/09638288.2025.2545594}, pmid = {40819293}, issn = {1464-5165}, abstract = {PURPOSE: This study aimed to develop a U.S.-specific reference equation for the 6-Minute Walk Test (6MWT) in individuals with Class III obesity and compare its performance with the Italian model by Capodaglio et al. The goal was to provide clinicians with a more accurate tool for assessing functional capacity.

METHODS: A retrospective review was conducted on 307 adults with Class III obesity referred to outpatient physical therapy from 2017 to 2023. Of these, 295 completed the 6MWT. Multiple linear regression was used to build a predictive model using age, sex, and BMI as independent variables. The model was validated via internal cross-validation and compared with Capodaglio et al.'s equation. Subgroup analyses by age group were also conducted.

RESULTS: The final model included age, BMI, and gender, explaining 41% of the variance in 6MWT distance. The mean absolute error was 53.2 meters, and the Spearman correlation was 0.67. Compared to Capodaglio's model, ours predicted 6.52% lower distances overall, with the largest differences in adults over 60.

CONCLUSION: The new U.S.-based model provides more accurate 6MWT predictions for individuals with Class III obesity, particularly older adults. It may help guide functional assessment and pre/post-metabolic and bariatric surgery care in this population.}, } @article {pmid40817431, year = {2025}, author = {SyBing, AB and Chen, H and Wang, DD}, title = {Re-Evaluation of Fixed Dosing Versus Body Size-Based Dosing Approaches for Large Molecule Therapeutics in Adults.}, journal = {Clinical pharmacology and therapeutics}, volume = {}, number = {}, pages = {}, doi = {10.1002/cpt.70015}, pmid = {40817431}, issn = {1532-6535}, abstract = {Wang et al.[1] (2009) and Zhang et al.[2] (2011) recommended a fixed dosing approach for large molecule therapeutics for first-in-human (FIH) trials, based on the finding that the majority of α values (body size effect on clearance) were < 0.5 across 12 monoclonal antibodies (mAbs) and 18 therapeutic proteins (TPs) and peptides, and fixed dosing provides advantages such as convenience, reduced medical errors, and cost-effectiveness. They also recommended that the approved dosing approach should be determined by α and the therapeutic window. This review aims to re-evaluate these recommendations using a larger dataset (N = 143) of diverse molecules. Results showed 62% (78/126) of non-ADC drugs were approved with fixed dosing, and 58% (28/48) of non-ADC drugs approved with body size-based dosing had an α < 0.7 where fixed dosing would be appropriate. Therefore, only the remaining 16% (20/126) of non-ADC drugs required body size-based dosing. In addition, the FIH dosing approach had significant implications on the approved dosing approach with 68% (90/133) of drugs using the same dosing approach in FIH and approval. Lastly, of non-ADC drugs evaluated, 56% (71/126) demonstrated a relationship between α and the approved dosing approach. When α did not explain the approved dosing approach, lack of clinically meaningful differences in exposure (49%, 27/55) was the most common justification. These findings confirm Wang et al.'s and Zhang et al.'s previous conclusions, continuing to support their recommendations. Based on these insights, a decision tree is proposed for selecting the appropriate dosing approach at each stage of drug development.}, } @article {pmid40813983, year = {2025}, author = {Wang, YT and Li, Q and Liu, JC and Chen, C and Ding, HX and Zha, X and Zhang, K}, title = {Cystatin F-a key player in central nervous system disease.}, journal = {Journal of neuroinflammation}, volume = {22}, number = {1}, pages = {203}, pmid = {40813983}, issn = {1742-2094}, support = {81901005//National Natural Science Foundation of China/ ; 81571046//National Natural Science Foundation of China/ ; 2022-MS-203//Natural Science Foundation of Liaoning Province/ ; JYTMS20230122//Basic Scientific Research Project of the Education Department of Liaoning Province/ ; LJKZ0755//Educational Department of Liaoning province/ ; 2023JH2/20200116//Department of Science & Technology of Liaoning province/ ; }, abstract = {Cystatin F is an endogenous cysteine protease inhibitor that belongs to the type II cystatin family. It has several unique characteristic structures that determine some of its specific functions. Cystatin F is expressed predominantly in peripheral immune cells and in the microglia of the central nervous system (CNS). Under physiological conditions, the expression of cystatin F in the CNS is minimal. However, emerging evidence suggests that it is significantly upregulated in several CNS diseases. Intriguingly, the role of cystatin F differs across disease contexts-serving a neuroprotective function while promoting pathological progression. Moreover, its function may shift across different pathological stages within the same disorder, reflecting a multifaceted pathophysiology. Cystatin F primarily acts by modulating neuroinflammation, clearing debris, and orchestrating immune responses via its selective expression in disease-associated microglia. As a vital player in CNS diseases, various intervention strategies targeting cystatin F have been proposed, including receptor-interacting protein kinase 1 pathway inhibition, miRNA targeting, mRNA stabilization, necroptosis inhibition, transcriptional regulation and upstream pathway modulation. Several approaches have yielded encouraging results in preclinical models, underscoring the therapeutic potential of modulating cystatin F activity. This review provides a comprehensive overview of the structural features, biological functions, and diverse roles of cystatin F in CNS diseases, including Alzheimer's disease, multiple sclerosis, Parkinson's disease, amyotrophic lateral sclerosis, stroke, Aicardi-Goutières syndrome, prion disease, and glioblastoma. Recent advances in therapeutic interventions focusing on cystatin F have been critically assessed, and key challenges related to clinical translation are outlined, offering new perspectives on therapeutic directions.}, } @article {pmid40813472, year = {2025}, author = {Satapathy, P and Mehta, R and Sah, R}, title = {Comment on "Outcomes of Percutaneous Cryoablation in Aneurysmal Bone Cysts: A Clinical and Imaging Analysis".}, journal = {Cardiovascular and interventional radiology}, volume = {}, number = {}, pages = {}, pmid = {40813472}, issn = {1432-086X}, abstract = {This commentary evaluates Shaikh et al.'s study on percutaneous cryoablation for aneurysmal bone cysts, highlighting its clinical relevance, strong methodology, and promising outcomes. It notes concerns about follow-up duration affecting fibrosis interpretation, limited subgroup analysis, and statistical power. The study supports cryoablation's safety and efficacy, while suggesting refinements for broader clinical adoption and future research.}, } @article {pmid40812494, year = {2025}, author = {Satapathy, P and Mehta, R and Sah, R}, title = {Comment on "Modified Eversion Carotid Endarterectomy is Potentially Associated with Improved Surgical Outcomes: Systematic Review and Meta-Analysis of the Clinical Efficacy of Modified Eversion Carotid Endarterectomy".}, journal = {Annals of vascular surgery}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.avsg.2025.08.002}, pmid = {40812494}, issn = {1615-5947}, abstract = {This commentary critiques Lee et al.'s meta-analysis on modified eversion carotid endarterectomy, noting selection bias, unadjusted follow-up outcomes, and a high risk of confounding factors. Although early stroke reduction appears promising, methodological flaws limit its clinical generalizability, necessitating well-designed randomized trials to validate its surgical efficacy.}, } @article {pmid40810164, year = {2025}, author = {Alo, B and Lamers, C}, title = {Crossing Barriers: Advancements in Macromolecular Therapeutics for Neurodegenerative Diseases and Strategies to Overcome the Blood-Brain Barrier.}, journal = {ACS pharmacology & translational science}, volume = {8}, number = {8}, pages = {2353-2383}, pmid = {40810164}, issn = {2575-9108}, abstract = {Neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis, present considerable challenges for our societies and health systems due to their progressive nature, the demographic shift toward older populations, and limited treatment options. Recent advances in macromolecular therapeutics, including antibodies, peptides, and proteins, offer novel therapeutic modalities for a broad range of diseases. Their high potency and specificity hold promise for disease-modifying therapies to combat neurodegenerative diseases. However, the blood-brain barrier poses a significant challenge for the effective delivery of these large molecules to the central nervous system. This review discusses the physiological role of the blood-brain barrier and its influence on restricting the exposure of macromolecules in the brain. Furthermore, emerging strategies for enhancing blood-brain barrier permeability to macromolecules are highlighted. This review summarizes modifications designed to utilize receptor-mediated uptake, adsorptive-mediated transcytosis, carrier-mediated transport, and nanoparticle-based delivery systems to overcome the blood-brain barrier. Additionally, we emphasize the importance of testing macromolecular therapeutics for their blood-brain barrier permeability and review the methods for such in vitro and in vivo testing. Finally, we shed light on therapeutics in preclinical and clinical development for neurodegenerative diseases and their challenges.}, } @article {pmid40808456, year = {2025}, author = {Frau, F and Bosia, M and Bischetti, L and Cappelli, G and Carotenuto, A and Diamanti, L and Montemurro, S and Agostoni, G and Bechi, M and D'Imperio, D and Lago, S and Noccetti, S and Simi, N and Ceroni, M and Iodice, R and Signorini, M and Arcara, G and Bambini, V}, title = {Ten years of using the APACS test: a multistudy cross-diagnostic analysis of pragmatic profiles and their relationship with Theory of Mind.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {380}, number = {1932}, pages = {20230495}, pmid = {40808456}, issn = {1471-2970}, abstract = {Pragmatic impairments are largely documented, yet rarely considered in clinical practice, also owing to a poor characterization of pragmatic profiles across conditions, as well as some overlap with theory of mind (ToM) in the conceptualization of pragmatics. Here, we present the outcome of a 10-year programme that started with creating a novel test, the Assessment of Pragmatic Abilities and Cognitive Substrates (APACS)-which we evolved by its application alongside ToM assessment in seven clinical groups (i.e. amyotrophic lateral sclerosis, multiple sclerosis, right-hemisphere stroke, Parkinson's disease, traumatic brain injury, schizophrenia and dyslexia). The multistudy cross-diagnostic analysis of 454 participants revealed that receptive pragmatic skills were impaired in all clinical groups compared with controls, with schizophrenia showing the most severely impaired profile, whereas expressive pragmatic skills were impaired in four neurological conditions (i.e. Parkinson's disease, amyotrophic lateral sclerosis, right-hemisphere stroke and traumatic brain injury). The association with ToM was limited to receptive pragmatics and was moderate in the whole sample. Overall, pragmatic impairment emerged as a diffuse feature of neurological and psychiatric illnesses, which contributes to defining complex socio-communicative phenotypes but cannot be equated to a social cognition deficit and should hence be the target of specific assessment and intervention.This article is part of the theme issue 'At the heart of human communication: new views on the complex relationship between pragmatics and Theory of Mind'.}, } @article {pmid40808423, year = {2025}, author = {Xia, K and Huang, N and Wang, Y and Zhang, G and Tang, L and Zhang, L and Yao, M and Liu, Z and Huang, T and Fan, D}, title = {Shared genetic link and causal inference between blood lipids, lipid-lowering drugs and amyotrophic lateral sclerosis.}, journal = {Neural regeneration research}, volume = {}, number = {}, pages = {}, doi = {10.4103/NRR.NRR-D-25-00266}, pmid = {40808423}, issn = {1673-5374}, abstract = {Growing evidence suggests that abnormal lipid metabolism occurs in amyotrophic lateral sclerosis, even in the presymptomatic stage, implying an etiologic link. However, the genetic mechanism underlying altered lipid levels in amyotrophic lateral sclerosis remains elusive. Therefore, in this study, we performed genetic correlation analysis, a cross-trait meta-analysis, tissue-specific enrichment analysis, and bidirectional two-sample Mendelian randomization analysis of European population to explore whether there is a genetic and causal relationship between lipids and amyotrophic lateral sclerosis. The effect of lipid-lowering drugs on amyotrophic lateral sclerosis was also evaluated using a drug target Mendelian randomization approach. The results showed a positive genetic correlation between amyotrophic lateral sclerosis and both high-density lipoprotein cholesterol and apolipoprotein A1 and identified 71 independent shared loci between amyotrophic lateral sclerosis and high-density lipoprotein cholesterol, as well as 55 independent shared loci between amyotrophic lateral sclerosis and apolipoprotein A1. These shared loci were enriched in the lipid metabolic pathway and the alcohol metabolic pathway. Further Mendelian randomization analysis targeting lipid-lowering drugs showed that single nucleotide polymorphisms within the ACLY and PCSK9 genes had a protective effect against amyotrophic lateral sclerosis risk by decreasing low-density lipoprotein cholesterol. The combination of ACLY and PCSK9 inhibitors has a greater protective effect on amyotrophic lateral sclerosis risk than that of PCSK9 inhibitors alone. In summary, there is a common genetic structure between lipids and amyotrophic lateral sclerosis. Mendelian randomization analysis supports an association between elevated blood lipids and the risk of developing amyotrophic lateral sclerosis, and the use of ACLY or PCSK9 inhibitors may improve disease prognosis.}, } @article {pmid40808411, year = {2025}, author = {Cheng, Y and Zhao, Y and Chen, C and Zhang, F}, title = {Metallothionein and neurodegenerative diseases.}, journal = {Neural regeneration research}, volume = {}, number = {}, pages = {}, doi = {10.4103/NRR.NRR-D-25-00011}, pmid = {40808411}, issn = {1673-5374}, abstract = {Neurodegenerative diseases, which mainly include Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Wilson's disease, and Huntington's disease, are a group of disorders characterized by loss of neurons in the brain and spinal cord. However, the underlying pathogenetic mechanisms of these disorders remain unclear. The metal ion hypothesis is considered a possible cause of a variety of neurodegenerative diseases. This hypothesis posits that the homeostatic imbalance of metal ions leads to oxidative stress, neuroinflammation, excessive aggregation of pathological proteins, and other serious consequences in neurons. The powerful endogenous metal ion chelator metallothionein plays an important role in regulating metal ion homeostasis to alleviate neurodegenerative diseases. This article provides an overview of the pathogenesis of neurodegenerative diseases in relation to metal ions such as copper, iron, and zinc and the contribution of metallothionein to the regulation of metal ion homeostasis. The review focuses on the role of metal ions in the course of neurodegenerative diseases and the molecular mechanisms through which endogenous metallothionein ameliorates metal ion overload to alleviate neurodegenerative diseases. A thorough understanding of these molecular mechanisms can provide a theoretical foundation for the development of new therapeutic strategies, with the aim of more effectively treating these devastating diseases in the future.}, } @article {pmid40808389, year = {2025}, author = {Petrovic, D and Perçin, G and Vilchez, D}, title = {Shuttle and stabilize: H1.2-FUS complex in amyotrophic lateral sclerosis pathogenesis.}, journal = {Neural regeneration research}, volume = {}, number = {}, pages = {}, doi = {10.4103/NRR.NRR-D-25-00422}, pmid = {40808389}, issn = {1673-5374}, } @article {pmid40807333, year = {2025}, author = {Godela, A and Rogacz, D and Pawłowska, B and Biczak, R}, title = {Natural Neuroinflammatory Modulators: Therapeutic Potential of Fungi-Derived Compounds in Selected Neurodegenerative Diseases.}, journal = {Molecules (Basel, Switzerland)}, volume = {30}, number = {15}, pages = {}, pmid = {40807333}, issn = {1420-3049}, abstract = {Neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis remain incurable. Current therapeutic strategies primarily focus on slowing disease progression, alleviating symptoms, and improving patients' quality of life, including the management of comorbid conditions. Over the past few decades, the incidence of diagnosed neurodegenerative disorders has risen significantly. As the number of affected individuals continues to grow, so does the urgent need for effective treatments that can halt or mitigate the progression of these diseases. Among the most promising therapeutic resources are bioactive compounds derived from fungi. The high quality of proteins, polysaccharides, unsaturated fatty acids, triterpenoids, sterols, and secondary metabolites found in fungi have attracted growing interest from researchers across multiple disciplines. One intensively studied direction involves the use of naturally occurring fungi-derived nutraceuticals in the treatment of various diseases, including neurodegenerative conditions. This article provides an overview of recent findings on fungal compounds-such as phenolic compounds, carbohydrates, peptides and proteins, and lipids-that may have potential applications in the treatment of neurodegenerative diseases and the alleviation of their symptoms.}, } @article {pmid40806339, year = {2025}, author = {Sonkodi, B}, title = {The Microbiota-Gut-Brain Axis in Light of the Brain Axes and Dysbiosis Where Piezo2 Is the Critical Initiating Player.}, journal = {International journal of molecular sciences}, volume = {26}, number = {15}, pages = {}, pmid = {40806339}, issn = {1422-0067}, abstract = {The current opinion paper puts into perspective how altered microbiota transplanted from Alzheimer's patients initiates the impairment of the microbiota-gut-brain axis of a healthy recipient, leading to impaired cognition primarily arising from the hippocampus, dysfunctional adult hippocampal neurogenesis, dysregulated systemic inflammation, long-term spatial memory impairment, or chronic pain with hippocampal involvement. This altered microbiota may induce acquired Piezo2 channelopathy on enterochromaffin cells, which, in turn, impairs the ultrafast long-range proton-based oscillatory synchronization to the hippocampus. Therefore, an intact microbiota-gut-brain axis could be responsible for the synchronization of ultradian and circadian rhythms, with the assistance of rhythmic bacteria within microbiota, to circadian regulation, and hippocampal learning and memory formation. Hippocampal ultradian clock encoding is proposed to be through a Piezo2-initiated proton-signaled manner via VGLUT3 allosteric transmission at a distance. Furthermore, this paper posits that these unaccounted-for ultrafast proton-based long-range oscillatory synchronizing ultradian axes may exist not only within the brain but also between the periphery and the brain in an analogous way, like in the case of this depicted microbiota-gut-brain axis. Accordingly, the irreversible Piezo2 channelopathy-induced loss of the Piezo2-initiated ultradian prefrontal-hippocampal axis leads to Alzheimer's disease pathophysiology onset. Moreover, the same irreversible microdamage-induced loss of the Piezo2-initiated ultradian muscle spindle-hippocampal and cerebellum-hippocampal axes may lead to amyotrophic lateral sclerosis and Parkinson's disease initiation, respectively.}, } @article {pmid40802439, year = {2025}, author = {Sousa, ES and Silva, LACD and Paiva, RM and Soares, KD and Azevedo, IC and Santos, VEP}, title = {Transitional Care for Patients with Amyotrophic Lateral Sclerosis to the Home: A Scoping Review.}, journal = {Revista brasileira de enfermagem}, volume = {78}, number = {3}, pages = {e20240297}, pmid = {40802439}, issn = {1984-0446}, abstract = {OBJECTIVES: to map the care required for the transition of patients with Amyotrophic Lateral Sclerosis to the home environment.

METHODS: a scoping review was conducted following the JBI guidelines. The search for publications on the topic was carried out in databases such as PubMed and Web of Science between February and May 2023. Full-text studies that addressed the research objective were included. Letters to the editor, editorials, and opinion articles were excluded.

RESULTS: the final sample consisted of seven articles. Regarding care, the studies highlighted assistance with basic life needs, care planning, protocol development, the use of telehealth, and communication between healthcare services.

CONCLUSIONS: the care required for the transition of individuals with Amyotrophic Lateral Sclerosis to the home environment ranges from assistance with basic human needs to the coordination with other healthcare services. Altogether, these actions contribute to a safe and effective transitional process.}, } @article {pmid40802083, year = {2025}, author = {Güvenç, U and Üney, G and Ünlü, N and Candan, Ö and Orman, G}, title = {Unveiling the limitations of OCT-based classification in diabetic epiretinal membranes: a call for integrative vascular and structural assessment with OCT-A.}, journal = {International ophthalmology}, volume = {45}, number = {1}, pages = {332}, pmid = {40802083}, issn = {1573-2630}, abstract = {PURPOSE: Govetto's optical coherence tomography (OCT)-based staging system is widely used for idiopathic epiretinal membranes (ERMs), but its applicability to diabetic ERMs remains unclear. Given the distinct microvascular pathology in diabetes, this study evaluated the system's applicability in diabetic ERMs and compared structural and vascular features of diabetic and idiopathic ERMs using OCT and OCT-angiography (OCT-A).

METHODS: This retrospective study included 142 eyes with diabetic ERM, idiopathic ERM, and healthy controls. All subjects underwent comprehensive ophthalmic examination, OCT, and OCT-A imaging. ERMs were staged using Govetto et al.'s classification. Correlations between visual acuity (VA), ERM stage, OCT metrics, and OCT-A parameters were analyzed. The macular vessel density ratio (MVR) was also calculated.

RESULTS: Ectopic inner foveal layer (EIFL), microcystoid changes, and retinal layer thicknesses were comparable across stages, with EIFL increasing as stages advanced in both groups. EIFL and outer foveal thickness showed no significant group differences, but EIFL was consistently thinner in diabetic cases. Diabetic ERMs had lower vessel densities (VD) and significantly reduced choriocapillaris flow area. Only in the diabetic group were strong correlations observed between outer retinal layer values and VD, as well as between VA, choriocapillaris flow, retinal thickness, and deep macular VD.

CONCLUSION: Although Govetto's OCT-based classification aligns with structural progression in both ERM types, it does not reflect the vascular alterations seen in diabetic ERMs. These findings suggest that structural staging alone may be insufficient in diabetic cases. Awareness of vascular differences and integration of OCT-A parameters may improve interpretation and guide prognosis in diabetic ERMs.}, } @article {pmid40800723, year = {2025}, author = {Jansen, J and Geijtenbeek, TBH and Kootstra, NA}, title = {Inducible HIV-1 Reservoir Reduction Assay (HIVRRA), a Fast and Sensitive Assay to Test Cytotoxicity and Potency of Cure Strategies to Reduce the Replication-Competent HIV-1 Reservoir in Ex Vivo PBMCs.}, journal = {Bio-protocol}, volume = {15}, number = {14}, pages = {e5384}, pmid = {40800723}, issn = {2331-8325}, abstract = {The HIV-1 reservoir, consisting of transcriptionally silent integrated HIV-1 proviruses, is a major barrier to a cure, as it persists during effective antiretroviral therapy (ART) and is the source of viral rebound upon treatment interruption. Some of the strategies explored for HIV cure focus on the identification of compounds to either reactivate and eliminate the HIV reservoir ("shock and kill") or to prevent HIV reservoir reactivation and induce deep proviral latency ("block and lock"). Paramount in developing these HIV-1 cure strategies is determining the effect of the compounds on the size of the inducible HIV-1 reservoir in blood from people living with HIV-1 (PWH). Traditionally, viral outgrowth assays have been the primary method to determine the inducible HIV-1 reservoir in CD4+ T cells from PWH. However, these assays are labor-intensive, time-consuming, and often have low sensitivity. We have recently developed the inducible HIV-1 reservoir reduction assay (HIVRRA), a rapid, cost-effective, and sensitive method to measure the impact of compounds on the inducible replication-competent HIV-1 reservoir in total peripheral blood mononuclear cells (PBMCs) from PWH ex vivo. The HIVRRA simultaneously evaluates the effect of test conditions on the size of the inducible replication-competent HIV-1 reservoir as well as the specificity and toxicity of the test strategy. Using total PBMCs instead of purified CD4+ T cells reduces processing time and resource requirements. This makes the HIVRRA a more practical, scalable tool for evaluating potential HIV-1 cure strategies. Key features • The HIVRRA builds on the TZM-BL cell-based assay to quantify the HIV-1 reservoir by Sanyal et al.'s [1] method. • The HIVRRA uses total PBMCs from PWH to determine infectious units per million cells. • The HIVRRA requires low PBMC input compared to other reservoir analysis methods. • The HIVRRA determines the toxicity of the compounds on HIV-1-infected and uninfected cells in the same assay.}, } @article {pmid40796877, year = {2025}, author = {Depuydt, L and Renders, L and Van de Vyver, S and Veys, L and Gagie, T and Fostier, J}, title = {b-move: faster lossless approximate pattern matching in a run-length compressed index.}, journal = {Algorithms for molecular biology : AMB}, volume = {20}, number = {1}, pages = {15}, pmid = {40796877}, issn = {1748-7188}, support = {1117322N//Fonds Wetenschappelijk Onderzoek/ ; RGPIN-07185-2020//Natural Sciences and Engineering Research Council of Canada/ ; 1SE7822N//Fonds Wetenschappelijk Onderzoek/ ; R01HG011392/NH/NIH HHS/United States ; R01 HG011392/HG/NHGRI NIH HHS/United States ; }, abstract = {BACKGROUND: Due to the increasing availability of high-quality genome sequences, pan-genomes are gradually replacing single consensus reference genomes in many bioinformatics pipelines to better capture genetic diversity. Traditional bioinformatics tools using the FM-index face memory limitations with such large genome collections. Recent advancements in run-length compressed indices like Gagie et al.'s r-index and Nishimoto and Tabei's move structure, alleviate memory constraints but focus primarily on backward search for MEM-finding. Arakawa et al.'s br-index initiates complete approximate pattern matching using bidirectional search in run-length compressed space, but with significant computational overhead due to complex memory access patterns.

RESULTS: We introduce b-move, a novel bidirectional extension of the move structure, enabling fast, cache-efficient, lossless approximate pattern matching in run-length compressed space. It achieves bidirectional character extensions up to 7 times faster than the br-index, closing the performance gap with FM-index-based alternatives. For locating occurrences, b-move performs ϕ and ϕ - 1 operations up to 7 times faster than the br-index. At the same time, it maintains the favorable memory characteristics of the br-index, for example, all available complete E. coli genomes on NCBI's RefSeq collection can be compiled into a b-move index that fits into the RAM of a typical laptop.

CONCLUSIONS: b-move proves practical and scalable for pan-genome indexing and querying. We provide a C++ implementation of b-move, supporting efficient lossless approximate pattern matching including locate functionality, available at https://github.com/biointec/b-move under the AGPL-3.0 license.}, } @article {pmid40795668, year = {2025}, author = {Gu, YG}, title = {Comment on "Nutrient enrichment by high aquaculture effluent input exacerbates imbalances between methane production and oxidation in mangrove sediments" by Dai et al. (Water Research 2025, 280: 123,552).}, journal = {Water research}, volume = {287}, number = {Pt A}, pages = {124360}, doi = {10.1016/j.watres.2025.124360}, pmid = {40795668}, issn = {1879-2448}, abstract = {We comment on Dai et al. (2025), who report that aquaculture-derived nutrient input increases methane (CH4) emissions and alters microbial communities in mangrove sediments, leading them to conclude that wastewater threatens the long-term carbon sink function of mangroves. While these findings are valuable, we argue that their conclusions overstate the risks to sedimentary carbon storage due to several methodological limitations in their experimental design and interpretation. Specifically, Dai et al.'s reliance on short-term CH4 flux data, without integrating sediment carbon accumulation measurements or biogeochemical controls (e.g., redox dynamics), limits the validity of their extrapolated conclusions regarding long-term carbon sink impairment. Drawing from both our own sediment core studies and broader biogeochemical principles, we argue that eutrophication-driven redox shifts can enhance, rather than impair, organic carbon and nitrogen burial under specific sedimentary conditions. We advocate for a more integrated methodological framework, including direct sediment carbon accumulation assessments and redox-sensitive proxies, when evaluating the carbon sink function of blue carbon ecosystems.}, } @article {pmid40794238, year = {2025}, author = {Jellinger, KA}, title = {Comorbid pathologies and their impact on progressive supranuclear palsy: current view.}, journal = {Journal of neural transmission (Vienna, Austria : 1996)}, volume = {}, number = {}, pages = {}, pmid = {40794238}, issn = {1435-1463}, support = {Society for the Promotion of Research in Experimental Neurology, Vienna, Austria//Society for the Promotion of Research in Experimental Neurology, Vienna, Austria/ ; }, abstract = {Progressive supranuclear palsy, a four-repeat tauopathy, is clinically characterized by early postural instability and falls, vertical supranuclear palsy, levodopa poorly-responsive parkinsonism, pseudobulbar palsy, and cognitive impairment. It is morphologically featured by accumulation of hyperphosphorylated tau protein in neurons and glia predominantly in the basal ganglia, brainstem tegmentum and frontal cortex, associated with degeneration of the extrapyramidal system and cortical atrophy. Isolated PSP neuropathology is uncommon, with nearly 70% showing co-neuropathologies including Alzheimer-type, Lewy body, TDP-43 pathologies, argyrophilic grains, and other tauopathies and neurodegenerative disorders (Parkinson disease, amyotrophic lateral sclerosis). The most common comorbid conditions are hypertension, cardiovascular and cerebrovascular diseases, diabetes mellitus, polyneuropathies, muscular and urological disorders. Due the increased prevalence of comorbidities and their eminent impact on the progress and outcome of the disease, clinical trials should account for them in their design and selection. However, currently little is known about co-pathologies in these patients. In view of the eminent burden of comorbidities and resulting therapeutic consequences, the frequency of the different co-pathologies in PSP and their clinical impact will be discussed. It should provide insight into their pathogenic backgrounds as a basis for adequate treatment procedures to improve the quality of life of patients with this fatal disease.}, } @article {pmid40791454, year = {2025}, author = {Storfer, A and Margres, MJ and Kozakiewicz, CP and Hamede, R and Ruiz-Aravena, M and Hamilton, DG and Comte, S and Stadler, T and Leaché, A and McCallum, H and Jones, M and Hohenlohe, PA}, title = {Response to "No evidence that transmissible cancer has shifted from emergence to endemism in Tasmanian devils".}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2025.07.14.664746}, pmid = {40791454}, issn = {2692-8205}, abstract = {Herein, we rebut the critique of Patton et al. (2020), entitled, "No evidence that a transmissible cancer has shifted from emergence to endemism", by Stammnitz et al. (2024). First and foremost, the authors do not conduct any phylogenetic or epidemiological analyses to rebut the inferences from the main results of the Patton et al. (2020) article, rendering the title of their rebuttal without evidence or merit. Additionally, Stammnitz et al. (2024) present a phylogenetic tree based on only 32 copy number variants (not typically used in phylogenetic analyses and evolve in a completely different way than DNA sequences) to "rebut" our tree that was inferred from 436.1 kb of sequence data and nearly two orders of magnitude more parsimony-informative sites (2520 SNPs). As such it is not surprising that their phylogeny did not have a similar branching pattern to ours, given that support for each branch of their tree was weak and the essentially formed a polytomy. That is, one could rotate their resulting tree in any direction and by nature, it would not match ours. While the authors are correct that we used suboptimal filtering of our raw whole genome sequencing data, re-analyses of the data with 30X coverage, as suggested, resulted in a mutation rate similar to that reported in Stammnitz et al. (2024). Most importantly, when we re-analyzed our data, as well as Stammnitz et al.'s own data, the results of the Patton et al. (2020) article are supported with both datasets. That is, the effective transmission rate of DFTD has transitioned over time to approach one, suggesting endemism; and, the spread of DFTD is rapid and omnidirectional despite the observed east-to-west wave of spread. Overall, Stammnitz et al. (2024) not only fail to provide evidence to contradict the findings of Patton et al. (2020), but rather help support the results with their own data.}, } @article {pmid40791023, year = {2025}, author = {}, title = {Correction to "Innovative Synchronous Spectrofluorometric Method for Assessing a Novel Drug Combination in Amyotrophic Lateral Sclerosis: In Vivo Human Application With Greenness and Sustainability Evaluation".}, journal = {Luminescence : the journal of biological and chemical luminescence}, volume = {40}, number = {8}, pages = {e70286}, doi = {10.1002/bio.70286}, pmid = {40791023}, issn = {1522-7243}, } @article {pmid40788946, year = {2025}, author = {Donjon, A and Boumendil, C}, title = {Using LEXY and LINuS Optogenetics Tools and Automated Image Analysis to Quantify Nucleocytoplasmic Transport Dynamics in Live Cells.}, journal = {Journal of visualized experiments : JoVE}, volume = {}, number = {221}, pages = {}, doi = {10.3791/68585}, pmid = {40788946}, issn = {1940-087X}, mesh = {*Optogenetics/methods ; *Active Transport, Cell Nucleus ; *Optical Imaging/methods ; Fluorescent Dyes ; Cell Culture Techniques ; }, abstract = {Nucleocytoplasmic transport (NCT) is essential for maintaining cellular homeostasis, and its disruption is involved in various diseases, including neurodegenerative disorders and amyotrophic lateral sclerosis. This underscores the need to develop tools to monitor and quantify NCT. Amongst these tools, the fast and reversible optogenetics probes, LEXY (light-inducible nuclear export system) and LINuS (light-inducible nuclear localization signal), allow the measurement of NCT dynamics in live cells. The original publications describe manual segmentation and quantification of the fluorescent probe signal in the nucleus and cytosol upon transfection of LEXY and LINuS constructs in live-cell imaging. However, both transfection and manual segmentation limit the number of cells that can be analyzed and are subject to imprecision due to potential user-dependent errors. While the high speed and reversibility provided by optogenetics should, in principle, allow for high sensitivity in detecting changes in NCT dynamics, it depends on the acquisition parameters and analysis of a sufficient number of cells. We have therefore established lentiviral vectors expressing LEXY and LINuS to create stable cell lines, tested live imaging markers and control conditions, and implemented a semi-automated image analysis pipeline that allows for the analysis of hundreds of cells. This analysis method uses the open-access software FIJI, is accessible to beginners in bioinformatics, and does not require advanced computer setups. Here we provide a step-by-step protocol to set up LEXY as an example of these optogenetic tools to monitor nuclear export, from preparation of the samples to live-cell imaging acquisition and automated analysis, while demonstrating how to adapt the protocol for other conditions, controls, or models in any lab. All plasmids and cell lines used in this protocol will be made available to the scientific community, therefore further increasing the accessibility of the method.}, } @article {pmid40787733, year = {2025}, author = {Raaphorst, J and Gullick, NJ and Shokraneh, F and Brassington, R and Min, M and Ali, SS and Gordon, PA}, title = {Non-targeted immunosuppressive and immunomodulatory therapies for idiopathic inflammatory myopathies.}, journal = {The Cochrane database of systematic reviews}, volume = {8}, number = {8}, pages = {CD015855}, pmid = {40787733}, issn = {1469-493X}, mesh = {Humans ; *Myositis/drug therapy ; *Immunosuppressive Agents/therapeutic use/adverse effects ; Randomized Controlled Trials as Topic ; Dermatomyositis/drug therapy ; *Immunomodulating Agents/therapeutic use/adverse effects ; Bias ; Child ; Adult ; Polymyositis/drug therapy ; }, abstract = {BACKGROUND: Idiopathic inflammatory myopathies (IIM) are autoimmune-mediated inflammatory disorders of skeletal muscles with non-muscle involvement in some people, which carry significant morbidity and mortality. Treatment of IIM represents an area of unmet need. This review is an update of a review previously published in 2012, as new and promising data on non-targeted treatments have emerged.

OBJECTIVES: To assess the effects (benefits and harms) of non-targeted immunosuppressant and immunomodulatory treatments for IIM: dermatomyositis (DM, including juvenile dermatomyositis, jDM), immune-mediated necrotising myopathy (IMNM), anti-synthetase syndrome (ASS), overlap-myositis (OM) and polymyositis (PM). We also included cancer-related myositis and amyopathic dermatomyositis.

SEARCH METHODS: On 3 February 2023, we searched the Cochrane Neuromuscular Specialised Register, CENTRAL, Embase, MEDLINE, ClinicalTrials.gov and WHO ICTRP. We intended to check references and citations, and contact experts to identify additional studies, but lacked the resources.

SELECTION CRITERIA: We included all randomised controlled trials (RCTs) or quasi-RCTs involving participants (adults and children) with IIM according to defined criteria. We included non-targeted immunosuppressants and immunomodulatory treatments alone or in combination, compared with a placebo, no treatment or another non-targeted immunosuppressant or immunomodulatory treatment. Our two primary outcomes were improvement of function or disability and improvement of muscle strength compared with baseline. By preference, we used the Health Assessment Questionnaire Disability Index (HAQ-DI) for disability and the Manual Muscle Test-8 (MMT8) score (adults or children) for muscle strength. Other outcomes were achievement of definitions of improvement (DOI) (the International Myositis Assessment and Clinical Studies (IMACS) Group or the more recent total improvement scores (TIS); for children, we reported achievement of improvement defined by the Paediatric Rheumatology International Trials Organisation (PRINTO)), cumulative corticosteroid dose, change in skin disease activity, serious adverse event and withdrawals for lack of benefit or adverse events.

DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methodology. To assess the risk of bias, we used the domain-based Cochrane risk of bias tool (RoB 1). We used fixed-effect models and, when needed, random-effects models for meta-analysis. We created summary of findings tables for any comparison for which data were available but prioritised comparisons of the following with placebo, no treatment or standard care: immunoglobulin, azathioprine and methotrexate. We included other comparisons as additional tables. We assessed the certainty of evidence using the GRADE approach.

MAIN RESULTS: We identified 16 studies (789 participants). The risk of bias in all but one study was high or unclear. Intravenous immunoglobulin (IVIg), compared to placebo, probably improves disability and muscle strength in participants with refractory IIM (standardised mean difference (SMD) 0.86, 95% confidence interval (CI) 0.51 to 1.21 (disability) and 0.78, 95% CI 0.43 to 1.13 (muscle strength); 3 RCTs, 136 participants; both moderate-certainty evidence). IVIg has a higher response rate based on American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) criteria than placebo (risk ratio (RR) 1.80, 95% CI 1.26 to 2.56; 1 RCT, 95 participants; moderate-certainty evidence). IVIg, compared to placebo, improves skin symptoms (Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) total activity score 0 to 100; higher worse) in people with refractory DM (mean difference (MD) -8.20, 95% CI -11.91 to -4.49; 1 RCT, 95 participants; moderate-certainty evidence). There may be more serious adverse events with IVIg than with placebo (RR 1.91, 95% CI 0.50 to 7.30; 2 RCTs, 144 participants; very low-certainty evidence), but little or no difference between IVIg and placebo in withdrawals for either lack of benefit or adverse events (RR 1.02, 95% CI 0.24 to 4.33; 3 RCTs, 154 participants; very low-certainty evidence). For azathioprine versus placebo, one study showed little or no effect of azathioprine on improvement in muscle strength, but the evidence was very uncertain (RR 1.33, 95% CI 0.43 to 4.13; 1 RCT; 16 participants; very low-certainty evidence). The evidence was also very uncertain for cumulative steroid dose (MD 12.06 mg/kg, 95% CI -6.09 to 30.21; 1 RCT, 16 participants; very low-certainty evidence). This early study did not assess IMACS DOI or CDASI or measure function or disability. Serious adverse events and withdrawals for either lack of benefit or adverse events were not systematically reported. For methotrexate, there may be little or no improvement in adults with DM or PM in function (Amyotrophic Lateral Sclerosis Functional Rating Scale 0 to 40, higher better) (MD 1.24, 95% CI -1.60 to 4.08; 1 RCT, 27 participants; very low-certainty evidence), muscle strength (MMT scale 0 to 80, higher better) (MD -5.68, 95% CI -12.94 to 1.58; 1 RCT, 27 participants; very low-certainty evidence), achievement of IMACS DOI (RR 1.01, 95% CI 0.74 to 1.39; 1 RCT, 27 participants; very low-certainty evidence). Cumulative steroid dose was measured, but the data could not be analysed, and change in CDASI was not measured. In children with new-onset jDM on a background therapy of prednisone, a higher proportion may achieve minimal improvement according to the PRINTO criteria with methotrexate than with placebo (RR 1.40, 95% CI 1.01 to 1.96; 1 RCT, 93 participants; low-certainty evidence). Serious adverse events may occur slightly more frequently with methotrexate (RR 1.48, 95% CI 0.54 to 4.07; 2 RCTs, 124 participants; low-certainty evidence). There may be fewer withdrawals for lack of benefit or adverse events with methotrexate (RR 0.62, 95% CI 0.37 to 1.05; 3 RCTs, 151 participants; low-certainty evidence).

AUTHORS' CONCLUSIONS: Our review shows improvement in disability, muscle strength and skin symptoms following IVIg in people with refractory DM (for PM, these data are not reliable; other subtypes have not been investigated in RCTs). The improvements related to IVIg in DM may be clinically meaningful, but the absence of established minimal clinically important differences (MCIDs) for both disability and muscle strength in IIM does not facilitate interpretation. For the other agents, the small number of trials of immunosuppressive and immunomodulatory therapies is inadequate to decide whether these agents are beneficial in IIM (excluding IBM). Our review shows room for improvement in the conduct and reporting of clinical trials in IIM, as well as the need to further investigate MCIDs for important outcome measures in IIM.}, } @article {pmid40787648, year = {2025}, author = {Mehta, R and Sah, R}, title = {Comment on "Healthcare-Seeking Behaviour for Obstetric Complications in Ethiopia: A Multilevel Mixed-Effect Analysis".}, journal = {Health services insights}, volume = {18}, number = {}, pages = {11786329251366920}, pmid = {40787648}, issn = {1178-6329}, abstract = {This commentary addresses methodological and interpretive limitations in Geremew et al.'s study on healthcare-seeking behaviour for obstetric complications in Ethiopia, emphasizing the need for clinically validated definitions, analytical exploration of variable interactions, inclusion of all obstetric events, and facility-level cross-validation to strengthen the policy relevance and accuracy of the findings.}, } @article {pmid40787603, year = {2025}, author = {Fonseca, I and Rueda, M and Cabanzo, C}, title = {The effect of dance interventions on well-being dimensions in older adults: a systematic review.}, journal = {Frontiers in sports and active living}, volume = {7}, number = {}, pages = {1594754}, pmid = {40787603}, issn = {2624-9367}, abstract = {BACKGROUND: Dance is increasingly recognized as a strategy that can support healthy aging. It incorporates physical, emotional, cognitive, and social engagement, which makes it particularly relevant for older populations. However, the effects of dance on multidimensional well-being have not yet been thoroughly synthesized.

OBJECTIVES: Systematically review empirical studies examining the effects of dance-based interventions on physical, emotional, cognitive, and social dimensions of well-being in older adults. We considered studies that assessed one or more of these dimensions as indicators of well-being.

DATA SOURCES: Studies were identified through database searches in Scopus, Web of Science, and SportDiscus conducted between October and November 2024.

Included studies were qualitative or quantitative empirical research published in peer-reviewed journals. Participants were adults aged 60 and older or identified as older adults. Interventions involved dance-based activities. Comparators included no intervention or alternative physical or recreational programs. The outcomes addressed at least one domain of well-being.

SYNTHESIS METHODS: This review followed the PRISMA 2020 guidelines. Eligibility criteria were defined using the PICOS framework. Study quality was assessed using Law et al.'s (1998) 16-item checklist. Due to methodological heterogeneity, a narrative synthesis was performed.

LIMITATIONS AND CONCLUSIONS: Although the results suggest that dance is a promising, low-cost intervention for promoting multidimensional well-being in older adults, several limitations should be noted. Many studies had small sample sizes or did not report effect sizes or randomization. Furthermore, some studies assessed only one or two dimensions of well-being rather than a multidimensional profile. This limits the scope of conclusions that can be drawn about integrated well-being. Future research should prioritize more rigorous designs, standardize multidimensional outcome measures, and assess long-term integrative effects to better inform health promotion policies.}, } @article {pmid40782717, year = {2025}, author = {Muller-Schoof, I and Meekes, W and Raaijmakers, N and Schellekens, M and Abdeselam Rocdi, Y and Luijkx, K}, title = {Implementing research findings into nursing homes: A mixed-methods study.}, journal = {International journal of nursing studies}, volume = {171}, number = {}, pages = {105179}, doi = {10.1016/j.ijnurstu.2025.105179}, pmid = {40782717}, issn = {1873-491X}, abstract = {BACKGROUND: As populations age worldwide, nursing homes face increasing pressure to deliver high-quality person-centered care for residents with complex needs. Despite advancements in implementation science, a significant theory-practice gap persists in nursing homes, where evidence-based practice adoption remains particularly slow among the predominantly practically-trained nursing staff.

OBJECTIVE: To identify implementation strategies currently used in nursing homes to integrate research findings into daily practice; and to explore the experiences, needs, and wishes of healthcare professionals and the experiences of implementation experts regarding research implementation.

DESIGN: An exploratory qualitative mixed-methods study.

SETTING: Nursing homes, with primary focus on The Netherlands.

PARTICIPANTS: Implementation experts from Academic Networks (n = 33) and healthcare professionals from nursing homes (n = 17).

METHODS: Data collection included: (1) eight focus groups and four interviews with implementation experts from the Collaborative Academic Networks for Care for Older Adults; (2) seventeen interviews with healthcare professionals; (3) analysis of 49 relevant documents from Academic Networks; and (4) a rapid review of 30 included articles. All data were systematically coded using Walter et al.'s (2003) taxonomy of implementation strategies and thematically analyzed through an iterative process. Data triangulation across sources enabled validation, while nursing home-specific adaptations emerged through constant comparison between empirical findings and the existing framework. Methodological rigor was enhanced through systematic coding by multiple researchers and regular team consensus meetings.

RESULTS: Nine implementation strategies were identified: dissemination, education, social influence, collaboration, incentives, evaluation, facilitation, mandating laws and regulations, and multifaceted initiatives. This study advances Walter et al.'s taxonomy by providing detailed nursing home-specific specifications of objectives, target groups, and approaches, including the valuable role of science practitioners as bridging agents and the need for facilitation approaches. Healthcare professionals expressed a need for practice-relevant research design with early stakeholder involvement, personalized feedback, accessible language, personal invitations to participate, and adequate support. Implementation wishes included dedicated internal organizational support, researcher involvement as advisors, collaborative plan development, sufficient resources, locally tailored solutions, and clear organizational communication.

CONCLUSION: This study delivers the first comprehensive overview of implementation strategies tailored to nursing home settings, providing researchers and practitioners with an expanded, evidence-based taxonomy. Three key insights emerge: implementation considerations must be embedded early in research design; multi-strategy approaches predominate and must be context-tailored; and stakeholder engagement requires reciprocal, continuous involvement throughout the research-implementation continuum, rather than one-directional consultation. This taxonomy serves as both a practical implementation tool and a foundation for advancing implementation science in nursing homes.}, } @article {pmid40780395, year = {2025}, author = {Wayment-Steele, HK and Ovchinnikov, S and Colwell, L and Kern, D}, title = {Does sequence clustering confound AlphaFold2?.}, journal = {Journal of molecular biology}, volume = {}, number = {}, pages = {169376}, doi = {10.1016/j.jmb.2025.169376}, pmid = {40780395}, issn = {1089-8638}, abstract = {Predicting multiple conformational states of proteins represents a significant open challenge in structural biology. Increasingly many methods have been reported for perturbing and sampling AlphaFold2 (AF2) [1] to achieve multiple conformational states. However, if multiple methods achieve similar results, that does not in itself invalidate any method, nor does it answer why these methods work. Interpreting why deep learning models give the results they do is a critically important endeavor for future model development and appropriate usage. To help the field continue to try to answer these questions, this work addresses misunderstandings and inaccurate conclusions in refs. [2-6]. Deep learning methods development moves quickly, and by no means did we think that the implementation of AF-Cluster in [7] would be the final word on how to sample multiple conformations. However, Porter et al.'s primary critique, that AF-Cluster does not use local evolutionary couplings in its MSA clusters, is incorrect. We report here further analysis that underscores our original finding that local evolutionary couplings do indeed play an important role in AF-Cluster predictions, and refute all false claims made against [7].}, } @article {pmid40779080, year = {2025}, author = {Huo, X and Wang, L and Ma, J and Wu, Z and Wang, K}, title = {Bibliometric analysis of publication trends in meningioma research (1992 - 2023).}, journal = {Neurosurgical review}, volume = {48}, number = {1}, pages = {595}, pmid = {40779080}, issn = {1437-2320}, support = {2024-4-2048//Capital's Funds for Health Improvement and Research/ ; 2022YFE0112500//National Natural Science Foundation of China/ ; 62027813//National Natural Science Foundation of China,China/ ; YGLX202518//Beijing Hospitals Authority Clinical medicine Development of special funding support/ ; }, mesh = {*Meningioma ; *Bibliometrics ; Humans ; *Meningeal Neoplasms ; *Biomedical Research ; }, abstract = {The purpose of this study was providing an overview of meningioma research and its current situation. We conducted a bibliometric study of 14,027 articles and reviews on meningioma between January, 1992 to June, 2023 with the bibliometrix tool and VOSviewer. The distribution of authorship and collaboration patterns among countries, institutions, publications, and authors were analyzed. Core sources was analyzed with Bradford's law and author productivity was analyzed with Lotka's Law. The current situation and key areas were assessed through co-occurrence analysis. The number of publications has steadily increased over the years. The United States and University California San Francisco made the most contribution country and institution, respectively. Among the cited authors, Zhang J. emerged as the leading contributor while Perry A. was the most productive. Black P.M. had the highest h-index and Nassiri F. ranked first among the m-index. The most frequently cited study was Louis D.N. et al.'s 2016 publication in Acta Neuropathologica, titled "The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary." The journals with the most published articles and most cited publications were World Neurosurgery and Journal of Neurosurgery, respectively. According to keyword analysis, treatment option, chemotherapy, NF2 gene and estrogen receptor, and progesterone receptor are becoming more popular. This study provided a comprehensive overview of meningioma research, as well as potential future research fields, such as the chemotherapy and NF2 gene.}, } @article {pmid40778462, year = {2025}, author = {Schvey, NA and Tanofsky-Kraff, M}, title = {Commentary on: The Prevalence of Eating Disorders and Disordered Eating in Adults Seeking Obesity Treatment: A Systematic Review With Meta-Analyses by Melville et al.}, journal = {The International journal of eating disorders}, volume = {}, number = {}, pages = {}, doi = {10.1002/eat.24522}, pmid = {40778462}, issn = {1098-108X}, abstract = {Melville et al.'s 2025 systematic review and meta-analysis highlight the prevalence of eating disorders and disordered eating among adults seeking obesity treatment. Findings showed that the prevalence of binge-eating disorder in obesity treatment-seeking samples exceeds community norms. Results corroborate prior research suggesting that high body weight and eating pathology frequently co-occur and that individuals seeking weight management may be a high-risk population for both sub- and full-threshold eating disorders. Although concerns persist that weight loss efforts may promote or worsen eating disorder symptoms, research indicates that structured, evidence-based interventions typically have neutral or positive effects on disordered eating outcomes. However, rigorous and consistent screening for eating disorders among individuals with high weight is lacking. Importantly, obesity and eating disorders share many common etiological factors, suggesting that integrated intervention is both feasible and highly beneficial. Despite this, the fields of obesity and eating disorders remain siloed. This bifurcation disproportionately impacts youth and adolescents who are at high risk for the onset of both conditions. Currently, standards of care fail to include screening for eating disorders, particularly in youth with high weight, who may be overlooked or misdiagnosed due, in part, to weight-based stigma. Universal, developmentally sensitive screening tools and comprehensive assessment of eating disorder risk factors are urgently needed in pediatric primary care settings. As evidence mounts for concurrent treatment models of high weight and eating disorders, integration across science and clinical care is vital to improve outcomes for youth affected by both conditions.}, } @article {pmid40777814, year = {2025}, author = {Sasaki, H and Yamamura, O and Onishi, H and Tsubouchi, H and Mizukami, Y and Kubota, M and Ikeda, R and Konoshita, N and Tanaka, T and Kishimoto, T and Kobayashi, K and Hayashi, H and Nishiyama, Y}, title = {Simple method for estimating low muscle mass in persons with bioelectrical impedance analysis measurement difficulties.}, journal = {Journal of clinical biochemistry and nutrition}, volume = {77}, number = {1}, pages = {91-98}, pmid = {40777814}, issn = {0912-0009}, abstract = {Bioelectrical impedance analysis cannot be used to measure muscle mass in some individuals. We aimed to determine cutoff values for low skeletal muscle mass index in sarcopenia diagnosis, based on the fat-free muscle mass index estimated using body fat percentage prediction equations, without relying on bioelectrical impedance analysis. The study included 564 residents from Wakasa, Fukui Prefecture, with a mean age of 76.0 ± 7.1 years. Body composition assessments using bioelectrical impedance analysis were conducted. Three prediction equations for body fat percentage (Ito et al., Deurenberg et al., and Gallagher et al.'s model for Asians) were applied. The cutoff value of the fat-free muscle mass index corresponding to low skeletal muscle mass index in sarcopenia diagnostic criteria was determined using receiver operating characteristic curves. Receiver operating characteristic curve analysis showed that the formula by Ito et al. yielded the highest area under the curve for estimating low skeletal muscle mass index in men, at 0.83. In women, the formulas by Ito et al. and Gallagher et al. performed similarly, each achieving an area under the curve of 0.779. The fat-free muscle mass index estimated using the body fat prediction formulas appear to be useful for screening low skeletal muscle mass index.}, } @article {pmid40776084, year = {2025}, author = {Rose, C and Davies, S and Arries-Kleyenstuber, E}, title = {The RAD Synthesis: Taxonomy and Decolonial Ethic of Emerging Digital Technologies for Nursing Informatics.}, journal = {Studies in health technology and informatics}, volume = {329}, number = {}, pages = {1387-1391}, doi = {10.3233/SHTI251066}, pmid = {40776084}, issn = {1879-8365}, mesh = {*Digital Technology/ethics ; *Nursing Informatics/ethics ; *Ethics, Nursing ; Humans ; }, abstract = {This paper is a response to Arries' call for exploration of a universal nursing ethics in the context of a pluralistic world, specifically consideration of an African ethics for nursing holding Ubuntu as a community-centred humanistic ideal with the "…ability to complement, extend and synthesize other ethical frameworks in nursing practice" [1]. Our discourse synthesizes the Arries-Davies taxonomy of ethical challenges of emerging digital technologies (EDTs) in healthcare [2] with sequential applications of Kwete et al.'s [3] colonial remnants framework and of Ubuntu [1][3][4][5]. This sequential synthesis of cognitive tools for identification, classification, and analysis of EDT ethical issues through a decolonial lens is dubbed the Rose-Arries-Davies (RAD) Synthesis. Key concepts explored include description of the Arries-Davies Taxonomy, introduction to the concept of colonial remnants, an introduction to Ubuntu, and demonstration of the RAD Synthesis to engage in decolonial critiques of global health informatics.}, } @article {pmid40775702, year = {2025}, author = {Seckin, M and Tiwana, R and Fry, D and Bailey, C}, title = {Key themes and approaches in palliative and end-of-life care education for the general public: a systematic review.}, journal = {BMC palliative care}, volume = {24}, number = {1}, pages = {219}, pmid = {40775702}, issn = {1472-684X}, support = {2683473//NHS England/ ; 2683473//NHS England/ ; 2683473//NHS England/ ; 2683473//NHS England/ ; }, mesh = {Humans ; *Terminal Care/methods/standards ; *Palliative Care/methods/standards ; }, abstract = {BACKGROUND: Families, friends, and communities play a vital role in supporting individuals facing declining health, caregiving duties, loss, or grief, especially with the growing desire to die at home. The general public can significantly impact end-of-life care and offer essential support mechanisms. This review aimed to explore and identify key educational components related to palliative and end-of-life care for citizens, volunteers, and the general public.

METHODS: A mixed-method systematic review was conducted, incorporating four electronic databases (MEDLINE, PsycINFO, CINAHL, and the Cochrane Library) and grey literature searches, and quality was assessed using Hawker et al.'s (2002) critical appraisal checklists.

RESULTS: Twenty studies published between 2011 and 2023 were included, covering topics in palliative, end-of-life care, and bereavement education. These studies involved a total of 10,307 participants and identified 16 different educational programmes for the public, volunteers, and lay caregivers. The analysis revealed six main themes: foundational concepts and philosophies, communication and decision-making, planning and preparation, symptom management, end-of-life care practices, and caregiving support.

CONCLUSIONS: This review highlights the importance of training programmes to improve community involvement in caregiving and enhance the quality of care for individuals with life-limiting conditions. Expanding access to such educational resources can empower more people to contribute confidently to end-of-life care in their communities.

PROSPERO-ID: CRD42024533124.}, } @article {pmid40772807, year = {2025}, author = {Sheppard, G and Boutis, K and Pusic, M}, title = {Response to the Commentary on Sheppard et al.'s Study of First Trimester POCUS Behaviors.}, journal = {Academic emergency medicine : official journal of the Society for Academic Emergency Medicine}, volume = {}, number = {}, pages = {}, doi = {10.1111/acem.70120}, pmid = {40772807}, issn = {1553-2712}, support = {ROMEO20210413//Memorial University of Newfoundland/ ; //Emergency Medicine Foundation-Council of Residency Directors/ ; }, } @article {pmid40772650, year = {2025}, author = {Zhang, Y and Guo, Z and Qiu, R and Ren, Z and Huo, J and Yang, Y and Qiao, B and Jiang, Z and Liu, T}, title = {The ConPET Mechanism Remains Veiled: Reply to "Unlocking the ConPeT Mechanism".}, journal = {Angewandte Chemie (International ed. in English)}, volume = {}, number = {}, pages = {e202514007}, doi = {10.1002/anie.202514007}, pmid = {40772650}, issn = {1521-3773}, support = {22171141//National Natural Science Foundation of China/ ; 22193010//National Natural Science Foundation of China/ ; 22193014//National Natural Science Foundation of China/ ; 21925103//National Natural Science Foundation of China/ ; 22271077//National Natural Science Foundation of China/ ; 020-63233022//Fundamental Research Funds for the Central Universities/ ; 24HASTIT001//Program for Science & Technology Innovation Talents in Universities of Henan Province/ ; }, abstract = {In this journal, a Correspondence by Ventura, Cozzi, and Ceroni reported time-resolved absorption spectroscopy studies in the electron transfer process from cyanoarene photocatalyst 3,4,5,6-tetrakis(diphenyl amino)phthalonitrile (4DPAPN) in the presence of tetrabutylammonium oxalate (TBAOx). This was used as a model reaction to investigate the mechanism of consecutive photoinduced electron transfer (ConPET) in our previously reported asymmetric [3+2] photocycloaddition. They proposed a new electron transfer pathway in which the electron from the excited state of the radical anion 4DPAPN*[•-] solvated in acetonitrile. This article replies to their Correspondence, including: the experimental and theoretical analysis on the driving force of electron transfer and a series of new experiments conducted with purer reagents under more stringent conditions, which suggest that the process of proton-coupled electron transfer (PCET) followed by ConPET cannot be excluded, as proposed in our previous publication. Yet, Ceroni et al.'s efforts to study organic photochemical reactions using time-resolved spectroscopy remain worthwhile, and their proposed mechanism also led us to consider other possible pathways for the reaction. This article concludes with a series of constructive suggestions for further studying the ConPET mechanism using time-resolved absorption spectroscopy and other techniques.}, } @article {pmid40758998, year = {2025}, author = {Jin, Y and Ganguly, P and Shea, JE and Buratto, SK and Bowers, MT}, title = {Aggregation of TDP-43307-319: A Dual Pathway to Forming Cylindrins and Fibrils and a Contribution to the Etiology of Amyotrophic Lateral Sclerosis.}, journal = {The journal of physical chemistry. B}, volume = {129}, number = {32}, pages = {8099-8114}, doi = {10.1021/acs.jpcb.5c02640}, pmid = {40758998}, issn = {1520-5207}, abstract = {The pathological aggregation of TAR DNA-binding protein of 43 kDa (TDP-43) is a hallmark of amyotrophic lateral sclerosis, and mutations within its low-complexity domain are known to influence its aggregation propensity and toxicity. Previous studies from our group and others have shown that TDP-43307-319 located at the C-terminus of TDP-43 is toxic and can form higher-order oligomers and fibrils. Of particular interest are the hexamers, which adopt a cylindrin structure that has been strongly correlated to neurotoxicity. In this study, we used a combination of ion mobility spectroscopy-mass spectrometry (IMS-MS), atomic force microscopy (AFM), and molecular dynamics simulations to probe the oligomer distribution resulting from the earliest times (the first 5 to 15 min) of incubation at varying concentrations for three different TDP-43307-319 mutations: wild-type (WT), A315T, and G314V. In this way, it was possible to trace the oligomer distributions at the initial stages of aggregation while avoiding the complication from aggregation-induced sedimentation over long periods. We found that both WT and A315T rapidly form stable hexamers and higher-order oligomers at low concentrations. As the concentration is increased, the IMS-MS oligomer distribution changes to favor small oligomers over the hexamers and higher-order oligomers for both WT and A315T. AFM shows that this shift in oligomer distribution is due to the formation of fibrils that are seeded by trimers and tetramers. This complex concentration dependence is attributed to two different kinetic paths: one at low concentration that favors the formation of hexamers/cylindrins and one at high concentration that favors fibril formation. Furthermore, the G314V mutation is nontoxic and does not show evidence of the two kinetic paths as hexamers are not formed at any concentration whereas fibril formation is observed at all concentrations.}, } @article {pmid40758298, year = {2025}, author = {Prpic, V}, title = {A "hidden gem" (Lidji et al., 2007) and future directions in embodied cognition.}, journal = {Journal of experimental psychology. Human perception and performance}, volume = {51}, number = {8}, pages = {994-995}, doi = {10.1037/xhp0001306}, pmid = {40758298}, issn = {1939-1277}, mesh = {Humans ; *Space Perception/physiology ; *Music ; *Pitch Perception/physiology ; *Cognition/physiology ; *Psychomotor Performance/physiology ; }, abstract = {Although the experiments and findings of Lidji et al. (2007) and Rusconi et al. (2006) are very similar, there is a detail in Lidji and colleagues' work with important implications for embodied cognition research. Specifically, Lidji et al. suggest that the vertical Spatial-Pitch Association of Response Codes effect is modulated by hand position and is stronger in musicians, particularly pianists. As the authors proposed, this is likely due to the influence of the keyboard structure, hence the article's title, "A Piano in the Head." In my view, this is a key finding of Lidji et al.'s study that is worth further investigation and discussion. (PsycInfo Database Record (c) 2025 APA, all rights reserved).}, } @article {pmid40758160, year = {2025}, author = {Nangare, NR and Katkar, A and Roy, K}, title = {Comment on "One-Anastomosis Versus Roux-en-Y Gastric Bypass in the Resolution of Comorbidities: A Non-inferiority Meta-analysis and Meta-regression".}, journal = {Obesity surgery}, volume = {}, number = {}, pages = {}, pmid = {40758160}, issn = {1708-0428}, abstract = {This commentary critiques the statistical framing and clinical implications of Ramos et al.'s meta-analysis comparing one-anastomosis and Roux-en-Y gastric bypass. While OAGB shows non-inferiority for type 2 diabetes remission under select conditions, its elevated risk of bile reflux and GERD limits its broad applicability. We emphasize the need for consistent non-inferiority thresholds and patient-specific surgical planning.}, } @article {pmid40757511, year = {2025}, author = {Rafiq, M and Bashir, A}, title = {Risk factors for mental health in Kashmir: a qualitative study.}, journal = {Journal of ethnicity in substance abuse}, volume = {}, number = {}, pages = {1-19}, doi = {10.1080/15332640.2025.2537176}, pmid = {40757511}, issn = {1533-2659}, abstract = {Mental health in Kashmir presents an alarming picture, with reports indicating that nearly 45% of the population experiences psychological distress. This research is undertaken to explore the mental health landscape of Kashmir's youth through Petraitis et al.'s (1995) theoretical framework which investigates various types of risk across various levels. To achieve this objective, themes were generated from in-depth interviews with the relevant stakeholders which were juxtaposed into this existing theoretical framework. Findings showed that while some risk factors are universal, yet Kashmir's transitioning into modernity poses unique mental health challenges. The implication of this study is that there is a need for adapting mental-health modalities through both top-down approaches (that is, culturally-adapting the existing therapeutic modalities) and bottom-up approaches (that is, making tradition palatable to modern sensibilities) in order to improve the mental health landscape of Kashmir.}, } @article {pmid40756428, year = {2025}, author = {Camanto, OJ and Campbell, L}, title = {Trust in close relationships revisited.}, journal = {Journal of social and personal relationships}, volume = {42}, number = {9}, pages = {2516-2544}, pmid = {40756428}, issn = {0265-4075}, abstract = {Trust is widely regarded as a fundamental psychological concept in the study of relationships yet-rather than being investigated as a primary, material focus-is often relegated to serving as a proxy for and/or a means to facilitate the exploration of aspects of relationship quality and functioning. We conducted two measurement-focused studies to garner deeper insight into the nature of trust in romantic relationships and explore an account of trust that reframes its development as a process of construction, rather than addition. In Study 1 (N = 494), we explored the nature and structure of the construct of trust as put forward by Rempel et al. (1985). In Study 2 (N = 847), we then confirmed our findings from Study 1 and, using measurement invariance techniques and a refined version of Rempel et al.'s (1985) assessment, investigated the extent to which the trust of individuals involved in newly-formed relationships (n Newly-formed = 387) versus individuals involved in long term relationships (n Long-term = 460) reflect different conceptualizations of the construct. Across both studies, we (a) identified a compilation of items reflecting key factors of trust-Predictability (3 items), Dependability (4 items), and Faith (10 items)-resembling Rempel et al.'s (1985) framework; and (b) found broad sameness in the construct of trust across newly-formed and long-term relationships but also some granular differences that potentially suggest how the construct may change across stages of relationship development.}, } @article {pmid40756105, year = {2025}, author = {Mazza, A and Voorrips, E and Hughes, G and Desender, K and Van den Bussche, E and Stuyck, H}, title = {Is Mental Effort Exertion Contagious? A Replication Study.}, journal = {Journal of cognition}, volume = {8}, number = {1}, pages = {43}, pmid = {40756105}, issn = {2514-4820}, abstract = {Daily, we perform activities in the presence of others (e.g., office work). While it's well-established that the mere presence of others can influence our performance, it is less clear whether others' performance, rather than just their presence, influences us. To address this, we replicated Desender et al.'s (2016) study, Is mental effort contagious?, and conducted a second experiment to follow up on our failure to replicate their findings. Desender et al. (2016) used a modified joint Simon task where two participants performed side by side. The manipulated participant completed an easy (mostly congruent trials) and a difficult (mostly incongruent trials) block, while the neutral participant completed two neutral blocks (equal proportion of congruent and incongruent trials). They found that the neutral participant mirrored the manipulated participants' mental effort, exerting more effort when the latter performed a difficult versus an easy task. In both Experiment 1 (exact replication; N = 176) and Experiment 2 (more demanding joint Simon task; N = 120), we failed to replicate this result even though the manipulated participants adjusted their mental effort as expected. We identified methodological explanations for this discrepancy in results, such as how conditions were counterbalanced in the original study, which likely produced carry-over effects, and limited visibility of participants' physiological cues. Moreover, the original study's effect vanished when re-analyzed with a more robust linear mixed model, suggesting their findings may not have been as reliable as initially thought. Our findings underscore the need for rigorous experimental designs and analyses in psychological research.}, } @article {pmid40742681, year = {2025}, author = {Fisher, CF and Byrne, M and Johnston, AM}, title = {Dogs (Canis familiaris) copy-all refine-later where children (Homo sapiens) overimitate.}, journal = {Journal of comparative psychology (Washington, D.C. : 1983)}, volume = {}, number = {}, pages = {}, doi = {10.1037/com0000426}, pmid = {40742681}, issn = {1939-2087}, support = {//Boston College/ ; }, abstract = {Overimitation is a social learning mechanism in which an observer replicates the actions of a communicative demonstrator even if some of the actions in the process are functionally irrelevant. While many consider overimitation a uniquely human mechanism, some scholars have hypothesized that domestic dogs may overimitate because of their shared evolutionary history and pedagogical learning structures with humans. Previous literature has presented conflicting evidence regarding the presence of overimitation in domestic dogs. This study expanded upon work by Johnston et al. (2017) and directly compared 3- to 5-year-old children and domestic dogs on the same overimitation task. For both dogs and children, we demonstrated an irrelevant action followed by a relevant action and examined how often subjects reproduced this sequence across four trials. Consistent with an overimitation pattern, children reproduced the irrelevant then relevant sequence at a constant rate across four trials. However, dogs decreased the rate with which they reproduced this sequence across trials-a change which is consistent with a copy-all refine-later strategy or simple exploration. These findings support those in Johnston et al.'s (2017) study and further support the hypothesis that dogs do not overimitate like children. (PsycInfo Database Record (c) 2025 APA, all rights reserved).}, } @article {pmid40739888, year = {2025}, author = {Hoyos, ME and O'Connor, M and Mery, CM and Carberry, K and Lamari-Fisher, A and Steward, E and Dillingham, C and Fraser, CD and Well, A}, title = {Prioritising gaps in care in the real-life journey of single ventricle CHD.}, journal = {Cardiology in the young}, volume = {}, number = {}, pages = {1-10}, doi = {10.1017/S1047951125101157}, pmid = {40739888}, issn = {1467-1107}, abstract = {BACKGROUND: Single ventricle CHD requires lifelong care, yet its broader impact on patients and families remains unclear. Engaging patients in care improvement can strengthen relationships and outcomes.

OBJECTIVES: This study evaluates how individuals with single ventricle CHD prioritise gaps in care based on personal and family impact.

METHODS: Using Mery et al.'s identified care gaps, a survey was distributed to parents of children with single ventricle CHD and adults with single ventricle CHD in English or Spanish. Participants rated each gap from 1(not important) to 10(extremely important), with a "Not Applicable" option. Responses were analysed using median, weighted, and total rating scores. Sociodemographic data were examined, and univariate analysis and a race/ethnicity and insurance matrix were conducted on parent responses.

RESULTS: Among 36 complete responses, 30(83.3%) were parents and 6(16.7%) patients. Most parents were female(29,96.7%), White non-Hispanic(24,80.0%), with 17(6.7%) having privately insured children. Median child age was 6.5[interquartile range: 3.0-12.8] years, and 55.3% had Hypoplastic Left Heart Syndrome. The highest-rated gap was "Uncertainty of prognosis in adulthood" (9.5[interquartile range: 8.0-10.0]). The lowest was "Pregnancy termination presented repeatedly" (1.0[interquartile range: 1.0-7.0]). Non-White parents rated "Transition to adult healthcare" (p = 0.017) and "Navigating resources" (p = 0.037) higher. Patients (median age 33.0 years) prioritised "Rescheduling surgical procedures" and "Transition to adult healthcare" (both 10.0). "Support in family planning" had the highest total rating score(12). The lowest-rated was "Limited guidance on transition to adolescence" (0.0[interquartile range:0.0-0.0]).

CONCLUSIONS: Patients and families prioritise care gaps differently. Aligning their perspectives with clinical expertise can guide tailored solutions to improve outcomes for single ventricle CHD patients.}, } @article {pmid40739866, year = {2025}, author = {Saad, A}, title = {Critical appraisal of Zhu et al.'s magnetic drive blood pump: Toward clinical translation.}, journal = {The International journal of artificial organs}, volume = {}, number = {}, pages = {3913988251360563}, doi = {10.1177/03913988251360563}, pmid = {40739866}, issn = {1724-6040}, } @article {pmid40738129, year = {2025}, author = {Döring, K and Satyavolu, S and Durisin, M and Götz, F and Lanfermann, H and Warnecke, A and Giesemann, A}, title = {Long-term evaluation of otosclerosis on temporal bone CT.}, journal = {RoFo : Fortschritte auf dem Gebiete der Rontgenstrahlen und der Nuklearmedizin}, volume = {}, number = {}, pages = {}, doi = {10.1055/a-2659-8853}, pmid = {40738129}, issn = {1438-9010}, abstract = {To assess the long-term progression of otosclerosis lesions on temporal bone CT, particularly with regard to lesion expansion, distribution, and changes in density.This retrospective study analyzed all patients who underwent HRCT or CBCT for the diagnosis of otosclerosis between 2012 and 2022. The study population was screened for the presence of follow-up imaging. Patients with available imaging over a period of five years were included in the study. Demographic data, clinical symptoms, and imaging findings were analyzed using descriptive statistics. The imaging findings were grouped according to otosclerosis subtype (fenestral, retrofenestral, or internal auditory canal (IAC)) and the long-term course of otosclerosis was assessed in terms of density and size.35 patients were included in a follow-up study with an average duration of 100 months (range: 62-168 months, 5 to 14 years) for otosclerosis. A total of 65 ears were affected. The patients were on average 48 ± 12.1 (range: 11-74) years old. Women (n= 24, 69%) were more than twice as likely to be affected as men (n= 11, 31%). Retrofenestral otosclerosis was the most common form (54%), followed by fenestral otosclerosis (40%). Otosclerosis around the IAC was significantly less common, accounting for just 6% of cases. In both fenestral and retrofenestral otosclerosis, an increase in otosclerotic volume between the initial and last follow-up imaging scans was observed in fewer than a third of cases (16% vs. 20.6%; Table 2). The density increased in some cases over time, affecting 24% of fenestral and 38.2% of retrofenestral cases. If the IAC was affected, imaging showed no changes in extent or density over time.Over the long term (five to 14 years), slight changes in density (increasing sclerosis) and size expansion can only be observed in approximately one third of patients. A progression from fenetral to retrofenestral otosclerosis was not documented in any of the cases. · There are no significant changes in density and volume increase in the long-term course of otosclerosis.. · Progression from fenestral to retrofenestral otosclerosis was not observed in any case.. · The slight morphological progression of CT lesions observed in individual cases in our study is consistent with the limited progression of hearing loss observed in two-thirds of the remaining patients in Ishai et al.'s study.. · Döring K, Satyavolu S, Durisin M et al. Long-term evaluation of otosclerosis on temporal bone CT. Rofo 2025; DOI 10.1055/a-2659-8853.}, } @article {pmid40736135, year = {2025}, author = {Katz-Dana, H and Shles, A and Friedman, N and Erez-Granat, O and Shiri, R and Fayyaz, J and Dana, E and Rosenbloom, E}, title = {Developing in situ large-scale simulation strategies for enhanced patient safety.}, journal = {Journal of healthcare risk management : the journal of the American Society for Healthcare Risk Management}, volume = {}, number = {}, pages = {}, doi = {10.1002/jhrm.70009}, pmid = {40736135}, issn = {2040-0861}, abstract = {The transition to a new emergency department (ED) facility can pose significant challenges to patient safety. This study utilized Colman et al.'s simulation-based clinical systems testing approach to identify latent safety threats (LSTs), ensure operational readiness, and enhance staff confidence in a newly constructed ED at an urban hospital. A three-stage framework comprising development, implementation, and evaluation phases was employed. A large-scale "day in a life" in situ simulation was conducted to test system integration and identify LSTs. Data from participants, observers, and facilitators were collected and analyzed to develop action plans. The simulation included 63 scenarios over 4 h, engaging 125 participants and 50 standardized patients. A total of 113 LSTs were identified, leading to the development of a detailed action plan. Feedback from staff was positive, with participants reporting increased confidence in providing safe patient care in the new facility. This approach successfully identified safety threats and enhanced staff preparedness, potentially informing future operational plans for transitions in healthcare facilities. The methodology and findings are generalizable to other healthcare facilities undergoing similar transitions, where system integration, safety evaluation, and staff readiness are key concerns.}, } @article {pmid40734622, year = {2025}, author = {Mwaniki, AW and Nyaboga, JM and Mecha, EO and Oyugi, B}, title = {Performance of community health volunteers during the COVID-19 pandemic: assessing the enablers and challenges in Machakos County, Kenya.}, journal = {Primary health care research & development}, volume = {26}, number = {}, pages = {e65}, doi = {10.1017/S1463423625100248}, pmid = {40734622}, issn = {1477-1128}, mesh = {Humans ; Kenya/epidemiology ; *COVID-19/epidemiology ; *Community Health Workers/standards/organization & administration ; *Volunteers ; Focus Groups ; SARS-CoV-2 ; Female ; Qualitative Research ; Male ; Pandemics ; Adult ; }, abstract = {AIM: This study explored the enablers and challenges influencing the performance of community health volunteers (CHVs) in Machakos County, Kenya, during the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic disrupted healthcare systems globally, with particularly severe impacts in developing countries. Community health workers (CHWs) played a critical role in crisis communication, community engagement, case detection, referrals, and maintaining care continuity. However, limited evidence exists on the factors enabling and hindering their performance during the pandemic.

METHODS: This study employed a convergent mixed-methods design, integrating focus group discussions (FGDs), in-depth interviews (IDIs), and structured data extraction from the Kenya Health Information System (KHIS). Analysis of the data was guided by Agarwal et al.'s conceptual framework for measuring community health workforce performance with the quantitative data being analyzed using descriptive statistics, while qualitative data being analyzed through thematic analysis.

FINDINGS: CHVs effectively disseminated COVID-19 information, addressed vaccine hesitancy, and mobilized communities, supported by training, supervision, and community recognition. Their efforts led to significant improvements in healthcare services, including increased household visits, immunizations, and maternal health referrals. Despite their contributions, CHVs faced challenges such as delayed stipends, limited resources, and occasional community stigma, which hindered performance. Social support networks, community appreciation, and priority healthcare access emerged as key enablers, fostering resilience and motivation. Improved reporting mechanisms also highlighted CHVs' expanded roles during the pandemic.

CONCLUSION: This study underscores the critical role of CHVs in sustaining healthcare services during the COVID-19 pandemic, despite facing financial, logistical, and social barriers. Their resilience and adaptability led to significant improvements in key health services, supported by effective supervision and training. Strengthening systemic support, integrating CHVs into long-term strategies, and enhancing community recognition are essential to maximize their impact in future health challenges.}, } @article {pmid40729899, year = {2025}, author = {Ronft, S and Beck, AK and Lachmann, T}, title = {Human-centric virtual lighting: Effects of color temperature and daylight simulation in virtual environments.}, journal = {Applied ergonomics}, volume = {129}, number = {}, pages = {104601}, doi = {10.1016/j.apergo.2025.104601}, pmid = {40729899}, issn = {1872-9126}, abstract = {As virtual environments and metaverse platforms transform human interaction, understanding how lighting influences perception and behavior in digital spaces is critical. This study investigates the effects of correlated color temperature (CCT) and virtual daylight on human evaluations of virtual environments across two complementary experiments: one conducted in an uncontrolled real-world setting and the other in a controlled laboratory environment. Building on principles of human-centric lighting (HCL), we propose a framework for human-centric virtual lighting (HCVL) to optimize user experience in immersive digital spaces. In Experiment 1, participants evaluated 12 renderings of virtual exhibition stands and meeting spaces under varied lighting conditions, using Flynn et al.'s semantic differential scale. The real-world setting prioritized ecological validity, with participants using personal devices (with, for example, heterogeneous brightness and resolution) and representing diverse demographics (22 nationalities, ages 20-58). Experiment 2 replicated the design in a controlled laboratory condition, utilizing standardized monitors, and a homogeneous participant group (German undergraduate students, ages 18-26). Both experiments assessed perceptions of warmth, brightness, spaciousness, and preference, with statistical analyses comparing warm vs. cool CCT and daylight vs. room lighting effects. Key findings revealed large effects of CCT on perceived brightness and medium effects on stimulation and spaciousness, aligning with physical lighting research. Virtual daylight elicited robust preferences, rated as brighter, more private and aesthetically appealing, reflecting innate human biases toward daylight. Crucially, the laboratory results confirmed the real-world findings but with greater consistency, underscoring the impact of device variability and demographic diversity on the result from real-world setting. This study makes three primary contributions: (1) Empirical validation of HCVL principles, demonstrating that the effects of CCT and daylight transcend environmental modality (physical vs. virtual); (2) A methodological framework for balancing ecological validity and experimental control in virtual lighting research; (3) Practical insights for virtual space designers, emphasizing the integration of user expectations (e.g., "conceptual lighting") and adaptive daylight simulations. These results bridge the gap between physical and virtual lighting research, offering actionable guidelines for creating immersive, well-being-oriented digital spaces. Future work should explore cultural and ambient moderators of HCVL to support inclusive virtual spaces design.}, } @article {pmid40729571, year = {2025}, author = {Qasim, S}, title = {Letter to Editor: Methodological Concerns in Saeed et al.'s Meta-Analysis on Role of Proton Pump Inhibitors for Upper Gastrointestinal Bleeding Prevention in Patients on Dual Antiplatelet Therapy.}, journal = {American journal of therapeutics}, volume = {}, number = {}, pages = {}, doi = {10.1097/MJT.0000000000002038}, pmid = {40729571}, issn = {1536-3686}, } @article {pmid40719968, year = {2025}, author = {Asadi, MR and Senmar, M and Shafiei Kisomi, Z and Hosseinkhani, Z and Ahmadi, AE and Mozafari, M and Oustam, F and Ahmadieh, A}, title = {The role of fear of intimacy and loneliness in predicting of academic enthusiasm in medical science students: a cross-sectional study from the Iran.}, journal = {Discover mental health}, volume = {5}, number = {1}, pages = {113}, pmid = {40719968}, issn = {2731-4383}, abstract = {BACKGROUND: Academic enthusiasm is one of the most effective factors in achieving the best in students' education. Therefore, this study aimed to determine the role of fear of intimacy and loneliness in predicting academic enthusiasm in medical science students. this descriptive-cross-sectional study was conducted among students of Qazvin University of Medical Sciences in iran, 2023-2024. The data was collected using the demographic profile checklist, Frederick et al.'s academic enthusiasm inventory, Russell's loneliness scale, and Thelen and Descunter's fear of intimacy scale. The data was analyzed using descriptive-analytical statistics and SPSS version 22 software.

RESULTS: In total, 212 (55.5%) of the 380 students participating in the study were female and the rest were male. The mean age of the students was (21.83 ± 9.97) years. According to the results, students' academic enthusiasm with an average of 42.79 ± 8.09, and a score of 45.0 out of 100 is average. Based on the results, the feeling of loneliness with a standard score of 45.0 and a mean of 47.02 ± 9.76, and fear of intimacy, with a standard score of 40.86 and a mean of 92.21 ± 20.17, are at the moderate and below-average levels, respectively. The results of univariate regression analysis showed that for one unit increase in loneliness score, the academic enthusiasm in students decreased by 0.17 (P < 0.001).

CONCLUSION: The results showed that in medical science students, academic enthusiasm and loneliness are at an average level, but the fear of intimacy in this group is below the average level. In addition, the results showed that the feeling of loneliness has a predictive role in academic enthusiasm, and as the feeling of loneliness increases, academic enthusiasm decreases. Based on this, students are expected to participate in cultural workshops, communication management and motivation to reduce feelings of loneliness and promote academic enthusiasm.}, } @article {pmid40719821, year = {2025}, author = {Nangare, NR and C, U and Roy, K}, title = {Comment on "Characteristics, mechanisms, and medicolegal perspectives of fatal cardiothoracic injuries in a tertiary care center".}, journal = {Forensic science, medicine, and pathology}, volume = {}, number = {}, pages = {}, pmid = {40719821}, issn = {1556-2891}, abstract = {This commentary appraises Sharif et al.'s prospective analysis of cardiothoracic trauma, commending its predictive model and forensic insights. We critically examine limitations in statistical validation, survival analysis interpretation, and causal attribution in mixed-mechanism deaths. Our discussion emphasizes the importance of model generalizability and temporal clarity to strengthen clinical decision-making and medico-legal applications.}, } @article {pmid40718374, year = {2025}, author = {Kas-Osoka, OA and Poitevien, P}, title = {Showing Up is Still Resistance: Contextualizing Black Trainee Resistance in Medical Education.}, journal = {Perspectives on medical education}, volume = {14}, number = {1}, pages = {423-426}, pmid = {40718374}, issn = {2212-277X}, mesh = {Humans ; *Education, Medical/methods/standards ; *Black or African American/psychology/ethnology ; *Racism/psychology ; Female ; Professionalism ; White ; }, abstract = {This commentary amplifies the contributions of Horton et al.'s study on Black physician trainees' professional resistance, situating it within the broader landscape of health professions education (HPE). As Black women physician-educators, we reflect on the profound resonance of the study's themes-resistance as survival, as existence, and as professionalism. Horton et al. employ Endarkened Storywork and Black quilting to not only document Black trainee experiences but to disrupt conventional research paradigms that marginalize their truths. This commentary argues that their work challenges the field to reimagine equity by centering marginalized voices, redefining resistance as a daily, embodied practice, and questioning research frameworks rooted in whiteness. We emphasize the urgency of methodological transformation in HPE and the ethical imperative to design and interpret data in ways that affirm rather than exploit minoritized communities. By framing the acts of showing up, mentoring, and refusing assimilation as legitimate resistance, this work redefines professionalism and provides a roadmap for institutional accountability. To advance equity, educators and researchers must not only study resistance-they must practice it.}, } @article {pmid40714289, year = {2025}, author = {Poliak, M and Chen, C and Gibson, E}, title = {Word and construction probabilities explain the acceptability of certain long-distance dependency structures.}, journal = {Cognition}, volume = {265}, number = {}, pages = {106265}, doi = {10.1016/j.cognition.2025.106265}, pmid = {40714289}, issn = {1873-7838}, abstract = {The factors that affect the acceptability of long-distance extractions have long been debated, with multiple accounts proposed. Liu et al. (2022) proposed a succinct probability-based account of a sub-class of these kinds of materials, wh-questions with long-distance dependencies across sentence-complement verbs (e.g., "What did Mary whine that John bought?"). The explanation that they proposed was that the acceptability of such sentences depends on the probability of the verb-frame of the intermediate verb (e.g., "whine that"). In the current work, we evaluate some potentially simpler probability-based accounts on Liu et al.'s original data set, and show how an alternative (but also probability-based) approach accounts for the data better. We replicate their experiment and conduct the same analysis on the new dataset, finding the same results. Finally, we apply the same analysis to wh-questions with predicate adjectives (e.g., "What was Mary glad that John bought?"), and again find similar results. We conclude that the acceptability of such constructions is higher the more probable the words and constructions that make up the sentence are.}, } @article {pmid40712472, year = {2025}, author = {Yousef, AM and Cantor-Cutiva, LC and Hunter, EJ}, title = {Mapping 74 years in acoustic analysis of voice disorders: A bibliometric review and future research directions.}, journal = {Journal of communication disorders}, volume = {117}, number = {}, pages = {106555}, pmid = {40712472}, issn = {1873-7994}, support = {R01 DC012315/DC/NIDCD NIH HHS/United States ; }, abstract = {PURPOSE: This paper conducts a bibliometric analysis to identify and examine the strengths, gaps, and trends in research on acoustic voice assessment for voice disorders.

METHODS: A bibliometric analysis was performed on journal articles about voice disorders and acoustic voice assessment in English, Spanish, and Portuguese using seven indexed databases. The analyzed bibliometric parameters included publication year, authors, institutions, countries, journals, subject areas, and keywords. VOSviewer software was used for keyword co-occurrence analysis and authorships network analysis. The initial search yielded 6532 publications, with 1253 relevant papers after screening (1951-2024).

RESULTS: Publications in acoustic voice assessment had 74 years of exponential growth (25 % published after 2021). The publishing journals covered 80 categories and subjects. Artificial Intelligence, though recent, was among the top journal subjects. Health conditions like dementia, Alzheimer's, Amyotrophic lateral sclerosis, and depression were underassessed compared to Parkinson's. The literature focused on four separate themes: physiology of voice-affecting conditions; speech acoustics for evaluating dysphonia; speech production measurements for treating voice disorders; machine learning integration for voice disorder assessment.

CONCLUSIONS: Taking a wide view of acoustic voice assessment demonstrated research strengths and gaps-highlighting where it is used and not used-and the co-occurrence of various voice assessment topics. These insights reveal future opportunities to implement acoustic voice assessment.}, } @article {pmid40712303, year = {2025}, author = {Arulmoorthy, MP}, title = {Navigating the diagnostic delay: optimizing timely biopsy and integrating NIR-based technologies for head and neck cancer.}, journal = {Oral oncology}, volume = {168}, number = {}, pages = {107518}, doi = {10.1016/j.oraloncology.2025.107518}, pmid = {40712303}, issn = {1879-0593}, abstract = {Lee et al.'s study critically explores the detrimental effects of diagnostic delays in head and neck cancer (HNC), focusing on patients who initially present through emergency departments (ED). The findings reveal that delayed biopsies, especially those performed more than 34 days after initial imaging, are associated with worse survival outcomes, highlighting the need for timely tissue diagnosis. Notably, the study identifies a 34-day threshold for biopsy completion that should guide clinical practice to improve patient prognosis. This commentary expands on the study's findings, emphasizing the importance of optimizing care coordination to minimize time from imaging to biopsy. Moreover, the integration of innovative diagnostic and theranostic technologies, particularly near-infrared (NIR) organic small molecules, presents a promising solution to expedite cancer diagnosis and treatment. NIR fluorophores, with their ability to penetrate deep tissues and provide real-time imaging, could significantly enhance the early detection and management of HNC, thereby reducing diagnostic delays and improving patient survival rates.}, } @article {pmid40711733, year = {2025}, author = {Granito, A and Muratori, P and Czaja, AJ}, title = {Autoimmune Hepatitis Treatment: Can Low-Dose Steroids Be Generalized?.}, journal = {Digestive diseases and sciences}, volume = {}, number = {}, pages = {}, pmid = {40711733}, issn = {1573-2568}, abstract = {We critically examine the implications of Aggarwal et al.'s study on low- versus high-dose prednisolone induction in autoimmune hepatitis (AIH). While acknowledging the study's contribution, this letter argues that the predominantly cirrhotic and often decompensated patient cohort limits the generalizability of its findings to the broader AIH population. We emphasize the potential influence of advanced liver disease on treatment response and side effect profiles, suggesting that similar efficacy between low- and high-dose prednisolone may not extend to all AIH patients. We contend that future research should prioritize more representative AIH cohorts across the spectrum of disease severity to establish universally applicable corticosteroid dosing strategies.}, } @article {pmid40709766, year = {2025}, author = {Albrecht, I and Gilissen, J and Robijn, L and Pype, P and Deliens, L and Chambaere, K}, title = {What determines quality in palliative sedation? A scoping review identifying elements contributing to palliative sedation quality.}, journal = {Palliative medicine}, volume = {}, number = {}, pages = {2692163251351534}, doi = {10.1177/02692163251351534}, pmid = {40709766}, issn = {1477-030X}, abstract = {BACKGROUND: Palliative sedation involves using sedatives to reduce consciousness until death. Though common in end-of-life care, it remains complex and controversial, with unclear quality parameters and limited guidance for improvement. A comprehensive overview of elements that reflect quality in palliative sedation is currently missing.

AIM: To identify quality reflecting elements for palliative sedation reported in peer-reviewed, indexed and gray literature.

DESIGN: Scoping review using Levac et al.'s methodological framework, including systematic searching, screening and narrative synthesis.

DATA SOURCES: Academic databases with indexed sources (MEDLINE, EMBASE, CENTRAL, CINAHL, PsycINFO) and databases also containing gray literature (MEDNAR, Web of Science) were searched between February and December 2023 for sources with primary data published after 2009, without restrictions on population or study design.

RESULTS: Among the 60 sources analyzed, 157 elements reflecting palliative sedation quality were identified and thematized into 22 themes and four overarching domains: (1) process elements of decision-making such as indication, proximity to death, timing, patient involvement, proactiveness, patient support, family involvement, artificial nutrition and hydration; (2) process elements of performance, such as level of sedation, medication use, monitoring, duration, care continuation, family support; (3) outcome elements covering patient comfort, family well-being, family satisfaction, professionals' well-being and satisfaction; (4) process elements of collaboration and documentation.

CONCLUSION: This scoping review found a broad range of elements reflecting palliative sedation quality - beyond clinical performance, sedation outcomes or patient level elements alone. These insights can inform the development of a core set of indicators to support quality monitoring in palliative sedation.}, } @article {pmid40705646, year = {2025}, author = {León, FR}, title = {How critics of racial hereditarian research (mis)categorize empirical studies: Commentary on Bird et al. (2024).}, journal = {The American psychologist}, volume = {80}, number = {5}, pages = {838-839}, doi = {10.1037/amp0001500}, pmid = {40705646}, issn = {1935-990X}, mesh = {Humans ; *Racism ; *Heredity ; *Empirical Research ; }, abstract = {According to Bird et al. (2024), racial hereditarian research (RHR) is scientific racism that should be curbed by the American Psychological Association. They presented an RHR bibliography in which I found eight works of Federico R. León addressing cognitive performance. The eight studies were animated by a socioecological rather than RHR perspective and two of them explicitly contradicted the racial/hereditarian position. I conclude that Bird et al.'s design of the RHR bibliographic classification was erroneous and counterproductive to their own aims and should be modified. I also suggest alternative ways to strengthen anti-RHR positions. (PsycInfo Database Record (c) 2025 APA, all rights reserved).}, } @article {pmid40705645, year = {2025}, author = {Anderson, AR}, title = {Applying the lifestyle lens to population mental health science: A commentary on Dodge et al. (2024).}, journal = {The American psychologist}, volume = {80}, number = {5}, pages = {835-837}, doi = {10.1037/amp0001536}, pmid = {40705645}, issn = {1935-990X}, mesh = {Humans ; *Mental Health ; *Life Style ; *Population Health ; *Health Promotion ; *Healthy Lifestyle ; }, abstract = {In response to Dodge et al.'s (2024) call for a new population mental health science, I propose that such an approach would be greatly benefited by focusing on the role of everyday lifestyle factors. In conjunction with the burgeoning evidence demonstrating the physical and mental health benefits of healthy lifestyles, applying a "lifestyle lens" to this endeavor would unify diverse providers and researchers in the common goal of healthy lifestyle promotion. A population health science built on a foundation of lifestyle could significantly impact many of the most common and pressing global physical and mental health challenges. (PsycInfo Database Record (c) 2025 APA, all rights reserved).}, } @article {pmid40704387, year = {2025}, author = {Punski-Hoogervorst, JL and Avital, A}, title = {Expanding the framework of attention in posttraumatic stress disorder: Commentary on Clauss et al. (2025).}, journal = {Journal of traumatic stress}, volume = {}, number = {}, pages = {}, doi = {10.1002/jts.70009}, pmid = {40704387}, issn = {1573-6598}, abstract = {This commentary expands on Clauss et al.'s (2025) meta-analysis of attention control training (ACT) for posttraumatic stress disorder (PTSD) by situating ACT and related interventions within a broader framework of attentional functioning. Although ACT and attention bias modification (ABM) show promise in targeting specific attentional processes, both neglect key domains, such as divided attention and multisensory regulation, which are often impaired in PTSD. Drawing on neuropsychological and neuroimaging findings, we highlight the need for the application of a multidimensional model of attention that accounts for the complexity of trauma-related attentional dysregulation. Future interventions should integrate a wider range of attentional components to improve clinical relevance and effectiveness.}, } @article {pmid40703412, year = {2025}, author = {Jablonowski, K and Hooker, B}, title = {Unadjusted Analysis of a Population-Based Study of Measles, Mumps, and Rubella Vaccination and Autism.}, journal = {Integrative medicine (Encinitas, Calif.)}, volume = {24}, number = {4}, pages = {10-12}, pmid = {40703412}, issn = {1546-993X}, abstract = {Madsen et al.'s unadjusted results do not support rejecting the causal link between the MMR (measles, mumps, and rubella) vaccine and autism. The summary statistics and errors in the original publication warrant the release of the raw data. Madsen et al. is a cornerstone publication that forms the basis of the claim that vaccines do not cause autism, and thus, correctness and transparency need to be ensured.}, } @article {pmid40702300, year = {2025}, author = {AlJuhani, AA and Desoky, RM and Binshalhoub, AA and Alzahrani, MJ and Alraythi, MS and Alzahrani, FF}, title = {Advances in postmortem interval estimation: A systematic review of machine learning and metabolomics across various tissue types.}, journal = {Forensic science, medicine, and pathology}, volume = {}, number = {}, pages = {}, pmid = {40702300}, issn = {1556-2891}, abstract = {BACKGROUND: Traditional postmortem interval (PMI) estimation methods rely on observable changes such as rigor mortis, livor mortis, and algor mortis but are often affected by environmental factors. Metabolomics, combined with techniques like nuclear magnetic resonance (NMR) and mass spectrometry, improves accuracy by identifying biochemical changes postmortem. Machine learning methods such as Principal Component Analysis (PCA), Partial Least Squares (PLS), and Support Vector Machines (SVMs), enhance PMI predictions by analyzing metabolite data. This review aims to summarize advances in using machine learning for PMI estimation and identify the optimal combination of tissue samples and algorithms for accurate predictions.

METHODS: We retrieved relevant articles up to September 2024 from PubMed, Scopus, Web of Science, IEEE, and Cochrane Library. Data were extracted from eligible studies by two independent reviewers. This included the number and species of subjects, tissue sample used, PMI range in the study, metabolic profiling technique, machine learning algorithms, potential PMI markers, and model performance.

RESULTS: We compared machine learning models for PMI estimation across various tissues. Zhang et al. (2022) had the best performance with a random forest (RF) model using cardiac blood, achieving a mean absolute error (MAE) of 1.067 h by selecting key metabolites. Wu et al. (2017) followed with an orthogonal signal-corrected PLS model (R[2] > 0.99, MAE 1.18-2.37 h). Lu et al. (2022) achieved 93% accuracy with a multi-organ stacking model. Other promising models include Zhang et al.'s (2017) nu-SVM on pericardial fluid (RMSE = 2.38 h) and Sato et al.'s (2015) PLS model on cardiac blood (MAE = 5.73 h).

CONCLUSION: Cardiac blood is best for short PMIs with random forest models, while skeletal muscle and stacking models excel for longer PMIs. Future studies should refine and validate these findings as well as extend the findings to human subjects.}, } @article {pmid40696825, year = {2025}, author = {Schmidt, R}, title = {Mind the Gaps: Revisiting the Validity, Consistency, and Scope of the Eating Disorder Examination. A Commentary on Reilly et al. (2025).}, journal = {The International journal of eating disorders}, volume = {}, number = {}, pages = {}, doi = {10.1002/eat.24509}, pmid = {40696825}, issn = {1098-108X}, abstract = {This commentary responds to Reilly et al.'s (2025) forum article and focuses primarily on Area of Focus #2: ensuring group-specific validity and adaptability of eating disorder assessment tools. Using the Eating Disorder Examination (EDE) as a case example, it is argued that psychometric flexibility must be accompanied by empirical accountability. Specifically, the commentary highlights the importance of testing measurement invariance (MI) to evaluate whether tools like the EDE function equivalently across different populations and time points. This is particularly relevant as the EDE or its self-report version (EDE-Q) are increasingly being used in populations for which they were not originally designed, for example, individuals with avoidant/restrictive food intake disorder or people of diverse gender identities. Additionally, the commentary discusses the need for harmonization between different versions of the instrument (EDE vs. EDE-Q), and calls for greater transparency in reporting and applying scoring conventions. A further consideration is the consistency of application across raters and research contexts, suggesting that interrater reliability should be examined more systematically across sites. Drawing on the metaphor of a long-serving but evolving vehicle, the commentary argues that modernization is necessary, but must not come at the cost of clinical depth or training relevance. Knowing how to drive remains essential, even when upgrading the vehicle.}, } @article {pmid40694206, year = {2025}, author = {Mahto, K and Kuwar, OK and Maloo, A and Kalia, N}, title = {Therapeutic potential of luteolin in neurodegenerative disorders: targeting Nrf2, NFĸB, MAPK, and JAK-STAT pathways to combat neuroinflammation and apoptosis.}, journal = {Inflammopharmacology}, volume = {}, number = {}, pages = {}, pmid = {40694206}, issn = {1568-5608}, abstract = {Neurodegenerative diseases, including Alzheimer's, Parkinson's, Huntington's disease, Multiple sclerosis and Amyotrophic Lateral Sclerosis, are characterized by progressive neuronal loss, oxidative stress, chronic neuroinflammation, mitochondrial dysfunction, and apoptosis. The Nrf2/ARE, IĸB/NFĸB, MAPK/AP-1, and JAK-STAT signaling pathways play a pivotal role in these pathological processes, making them promising therapeutic targets. Luteolin, a naturally occurring flavonoid, has demonstrated potent antioxidant, anti-inflammatory, and neuroprotective properties by modulating these interconnected pathways. Activation of Nrf2/ARE signaling by luteolin enhances cellular antioxidant defences, while its inhibition of NFĸB, MAPK/AP-1, and JAK-STAT pathways suppresses neuroinflammation and apoptotic signalling, thereby mitigating neuronal damage. Emerging evidences suggest that luteolin effectively reduces neurotoxic effects by regulating inflammatory cytokine production, stabilizing mitochondrial function, and maintaining redox homeostasis. Its ability to interfere with crosstalk between these signaling pathways highlights its potential as a multi-targeted neuroprotective agent. Preclinical studies have provided strong evidence supporting luteolin's role in mitigating neurodegeneration, suggesting its applicability in neurodegenerative disease management. These findings underscore the therapeutic potential of luteolin in neurodegenerative diseases by targeting multiple pathological mechanisms. However, further investigations are needed to fully elucidate its molecular mechanisms and optimize its therapeutic benefits.}, } @article {pmid40694109, year = {2025}, author = {Levy, G and Schizas, C}, title = {Use and misuse of the sedimentation sign in lumbar spine stenosis.}, journal = {European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society}, volume = {}, number = {}, pages = {}, pmid = {40694109}, issn = {1432-0932}, abstract = {PURPOSE: The nerve root sedimentation sign (SedSign), introduced in 2010, is a radiological marker for lumbar spinal stenosis (LSS) on MRI. Despite widespread adoption, methodological inconsistencies in its application across studies have raised concerns about validity. This systematic review evaluated the accuracy of SedSign definitions and their impact on conclusions in published research.

METHODS: PubMed and Google Scholar were searched for articles utilising the SedSign. Definitions and illustrations were independently assessed by two authors against Barz et al.'s original criteria, classified as accurate, inaccurate, or absent. Study conclusions regarding SedSign's clinical and radiological utility were categorised as positive or negative. Journal metrics were analysed for correlation with reported accuracy.

RESULTS: Only 14 out of 31 studies applied the SedSign definition correctly. Of the 21 studies endorsing its utility, 10 used inaccurate definitions. Notably, 3 of 5 studies dismissing its value also misapplied the criteria. Inaccurate reporting showed no significant association with journal metrics.

CONCLUSION: Frequent misapplication of the SedSign in the literature may impact the reliability of research on lumbar spinal stenosis-even in high-impact journals. These findings expose a critical need for stricter adherence to validated radiological criteria and more vigilant peer review. Professional societies may play a key role in the future by developing comprehensive open-access guidelines to support researchers and reviewers in the standardized application of gradings and classifications, thereby enhancing consistency across studies. Ensuring methodological rigour is essential to minimise misleading conclusions with potential clinical implications.}, } @article {pmid40690850, year = {2025}, author = {Sharma, A and Raj, R}, title = {Treatment comparisons for MS fatigue: A network meta-analysis in light of Toljan et al.'s findings.}, journal = {Multiple sclerosis and related disorders}, volume = {102}, number = {}, pages = {106618}, doi = {10.1016/j.msard.2025.106618}, pmid = {40690850}, issn = {2211-0356}, } @article {pmid40690785, year = {2025}, author = {Gates, KE and Mefferd, AS and Stipancic, KL}, title = {Exploring Methodological Decisions for Calculating the Minimally Detectable Change in Dysarthria: Reliability, Statistics, and Standard Error of Measurement.}, journal = {Journal of speech, language, and hearing research : JSLHR}, volume = {68}, number = {8}, pages = {3771-3788}, doi = {10.1044/2025_JSLHR-24-00899}, pmid = {40690785}, issn = {1558-9102}, abstract = {PURPOSE: The minimally detectable change (MDC), widely used in rehabilitation sciences to interpret changes in outcome measures, is calculated using a reliability method, reliability statistic, and standard error of measurement (SEM). This study examined how different methodological choices affect MDC thresholds of speech intelligibility in speakers with dysarthria. The goals of this study were to compare MDCs calculated using (a) three different reliability methods, (b) two different reliability statistics, and (c) three different SEM calculations.

METHOD: Recordings of the Speech Intelligibility Test from 200 speakers including speakers with amyotrophic lateral sclerosis (n = 16), Huntington's disease (n = 44), multiple sclerosis (n = 60), and Parkinson's disease (n = 40), along with healthy controls (n = 40), were drawn from two databases. Thirty inexperienced listeners completed two sessions, providing orthographic transcriptions of 20 speakers. MDCs of intelligibility were calculated using (a) three reliability methods (i.e., test-retest, split-half, and intrarater), (b) two reliability statistics (i.e., Pearson r and intraclass correlation coefficients [ICCs]), and (c) three different formulas for calculating the SEM. Kruskal-Wallis tests were used to assess the effects of reliability methods, statistics, and SEM calculations.

RESULTS: Significant differences were found between the MDCs when using split-half and test-retest reliability, when using Pearson r and ICC, and when using two of the three SEM calculations.

CONCLUSIONS: Results demonstrate that methodological decisions can impact MDCs of speech intelligibility in speakers with dysarthria, highlighting the need for specific, detailed reporting of methodology used to calculate MDCs in future work. Findings can provide methodological guidance for future studies and contextualize existing research on intelligibility changes.}, } @article {pmid40686030, year = {2025}, author = {Donders, J and Piccoli, K}, title = {Utility of two new embedded measures of performance validity for the Wisconsin Card Sorting Test-64.}, journal = {The Clinical neuropsychologist}, volume = {}, number = {}, pages = {1-12}, doi = {10.1080/13854046.2025.2536156}, pmid = {40686030}, issn = {1744-4144}, abstract = {Objective: We sought to determine the utility of two new embedded validity indices for the Wisconsin Card Sorting Test-64 (Henry, 2024; Kosky et al., 2022). The goal was to determine if these proposed indices would be associated with specificity ≥ .90, sensitivity ≥ .40, and positive likelihood ratio of ≥ 2, in a clinical traumatic brain injury (TBI) sample with a broad range of injury severity. Method: We used logistic regression to investigate how well each new index could distinguish performance validity classification of 173 persons with TBI who were evaluated within 1-36 months after injury. Participants were classified based on at least two independent performance validity tests as having provided valid performance (n = 146) or invalid performance (n = 27). Results: Both indices had acceptable Likelihood Ratios. The Kosky et al. index had suboptimal sensitivity and specificity, while the Henry index had acceptable sensitivity (.41) and better specificity (.88). However, when either index, considered in isolation or combined, indicated invalid performance, it was most often a false positive. Conclusion: Kosky et al.'s index did not meet the a priori criteria. While the Henry index was more robust, more than half (18/29) of the cases it identified as invalid were false positives. Differences in base rates between the original sample of Henry and the current one likely affected positive predictive power of the new index. Results suggest that this index is more useful to rule out invalid performance than to rule it in.}, } @article {pmid40683999, year = {2025}, author = {Zhang, L}, title = {Association of aerobic exercise habits with higher albumin-globulin ratio and lower cellular immune-inflammatory markers: implication of the preventive effect of aerobic exercise on atherosclerotic cardiovascular disease.}, journal = {Heart and vessels}, volume = {}, number = {}, pages = {}, doi = {10.1007/s00380-025-02585-9}, pmid = {40683999}, issn = {1615-2573}, abstract = {This correspondence identifies irreconcilable contradictions in Tani et al.'s article (Heart Vessels. 2025;40:509-522) that critically undermine its conclusions. Key concerns include paradoxical relationships between smoking and albumin-globulin ratio (AGR), discordant liver enzyme patterns, and inconsistent inflammatory marker responses. Alternative mechanisms involving humoral suppression and hepatic adaptation better explain the findings. The study's cross-sectional design cannot resolve these discrepancies, necessitating longitudinal validation before clinical interpretation.}, } @article {pmid40681787, year = {2025}, author = {Battistone, MJ and Maggio, LA and Konopasky, A}, title = {"There Is No Getting Perfect at It": Discussing Intellectual Humility with Academic General Internal Medicine Ward Attendings.}, journal = {Journal of general internal medicine}, volume = {}, number = {}, pages = {}, pmid = {40681787}, issn = {1525-1497}, support = {3HPE052021B//U.S. Department of Veterans Affairs/ ; }, abstract = {BACKGROUND: Physicians face two conflicting goals-demonstrating competence and showing awareness of their limits (intellectual humility [IH]). While competence has been studied extensively in health professions education (HPE), IH remains relatively unexamined, especially in relation to physician and trainee experiences. This gap is important because IH may improve quality of care by mitigating against premature closure in diagnosis and strengthening therapeutic relationships by demonstrating respect for patients' perspectives. This study addresses this gap by exploring academic hospitalists' experiences of IH, to facilitate trainees and clinicians engaging in IH in ways that avoid detrimental emotions (e.g., shame) and negative repercussions (e.g., remediation).

OBJECTIVE: To explore academic hospitalists' experiences of IH, focusing on work with students and residents.

DESIGN: Qualitative analysis of semi-structured interviews.

PARTICIPANTS: Twelve hospitalists (6 women, 6 men) at an academic medical center who supervise medical students and residents on general medicine teams.

APPROACH: We conducted virtual, semi-structured interviews, asking participants to share experiences in which IH was anticipated, experienced, or observed, including when they were aware of personal limitations and when their opinions differed from peers' or learners.' Transcripts were independently coded by two team members; regular meetings were held to discuss interpretations. Analysis was guided by Porter et al.'s work; the authors initially applied her six content categories derived through characterizations of IH surveys while remaining open to additional codes.

KEY RESULTS: Transcripts contained all six content categories Porter identified, but also additional themes including (1) mitigation of personal limitations, (2) anxiety, (3) arc of career, (4) modeling, and (5) psychological safety.

CONCLUSIONS: Lived experiences of hospitalists contain themes substantially different from those of IH surveys. HPE has unique affordances and constraints affecting IH, even for attending physicians. Conceptualizations of competence that include IH provide direction for stronger relationships, shared decision-making, and responsible action in high-stakes situations.}, } @article {pmid40676615, year = {2025}, author = {Mousavi, SK and Kamali, M}, title = {Explaining reasons for cheating in exams among undergraduate nursing students: a qualitative study.}, journal = {BMC medical education}, volume = {25}, number = {1}, pages = {1075}, pmid = {40676615}, issn = {1472-6920}, mesh = {Humans ; Qualitative Research ; *Students, Nursing/psychology ; *Deception ; *Education, Nursing, Baccalaureate ; Female ; *Educational Measurement ; Male ; Interviews as Topic ; Adult ; Young Adult ; }, abstract = {INTRODUCTION: Cheating in exams is a common problem in many educational settings. This issue is critical in the medical field because it can have a long-term impact on the health of society. Therefore, this study aims to explore the reasons why undergraduate nursing students cheat in exams.

METHODS: This qualitative content analysis study was conducted in 2024, involving 15 participants, comprising six undergraduate nursing students, five faculty members, a dean of the nursing college, a vice-chancellor of educational affairs, an expert in educational affairs, and an in-charge for exam administration, who were purposefully selected. Individual, in-depth, semi-structured interviews were conducted to collect information. Then, the data was analyzed using Elo and Kyngas' inductive content analysis approach with the help of MAXQDA 2020 software. Also, Elo et al.'s checklist was used to check the trustworthiness of the data.

RESULTS: The number of extracted final codes was 96, which were divided into two main themes and four categories, including personal (intrapersonal and interpersonal) and organizational factors (weakness in educational policies and implementation problems).

CONCLUSION: These findings can significantly influence the development of future educational policies and practices. Therefore, educational policymakers should pay special attention to this issue and take adequate measures to address the root causes of exam cheating.}, } @article {pmid40675519, year = {2025}, author = {Sheng, R and Tao, S and Jin, C}, title = {Unveiling the m[6]A regulatory axis in cigarette smoke-induced carcinogenesis: A landmark analysis in toxicology letters.}, journal = {Toxicology letters}, volume = {411}, number = {}, pages = {78-79}, doi = {10.1016/j.toxlet.2025.07.1407}, pmid = {40675519}, issn = {1879-3169}, mesh = {Humans ; *Smoke/adverse effects ; *Carcinogenesis/chemically induced/genetics ; Methyltransferases/genetics/metabolism ; A549 Cells ; Cytochrome P-450 CYP1A1/genetics/metabolism ; }, abstract = {This commentary highlights Nakano et al.'s significant study demonstrating that cigarette smoke extract (CSE) downregulates METTL3/METTL14, altering m[6]A RNA modification and establishing a novel regulatory axis where m[6]A dynamics control ARNT transcription via chromatin remodeling in A549 cells. The work provides important mechanistic insights linking environmental exposure to epitranscriptomic dysregulation relevant to carcinogenesis, particularly CYP1A1 induction. While technically rigorous and identifying m[6]A machinery as potential investigative targets, limitations include the A549 cell model, incomplete FTO characterization, dose-response, and CSE comparability to whole smoke. The findings underscore the need for follow-up studies to explore the therapeutic potential cautiously.}, } @article {pmid40668002, year = {2025}, author = {Uppal, P and Reed, D and Warwick, C}, title = {A framework for international Medical Graduate success in the applied Knowledge test: approach, awareness, assistance and application - a focus group study.}, journal = {Education for primary care : an official publication of the Association of Course Organisers, National Association of GP Tutors, World Organisation of Family Doctors}, volume = {}, number = {}, pages = {1-9}, doi = {10.1080/14739879.2025.2524809}, pmid = {40668002}, issn = {1475-990X}, abstract = {INTRODUCTION: Differential attainment (DA) is the disparity between attainment levels of different groups of doctors. The causes are multi-factorial, and variations have been highlighted between International Medical Graduate (IMG) General Practice Registrars (GPRs) and United Kingdom Medical Graduates (UKMGs) in their performance of the UK licensing examination for general practice, the Applied Knowledge Test (AKT). Despite existing support measures, there remains a gap in understanding the effectiveness of interventions aimed at improving examination success for IMGs in the AKT.

AIM: To explore the preparation and support methods that IMG GPRs consider contributed to their AKT examination success.

METHODS: A qualitative study using focus groups and Green et al.'s (2007) model of Thematic Analysis was used to generate codes, categories and themes. The verification techniques of member checking and inter-rater reliability were implemented.

RESULTS: Four focus groups with a total of 13 IMG GPRs were undertaken. Four primary themes emerged from the thematic analysis: 'Awareness of Preparation Required', 'Assistance that Aids AKT Examination Success','Application of Knowledge Gained and Individual Preferences' and 'Approach and Individual Influences'.

CONCLUSIONS: This study highlights the perceived importance of personal motivation, early awareness, and proactive support from peers and educators for IMG GPRs to succeed in the AKT. The model of the '4As' (Approach, Awareness, Assistance, and Application) was developed to aid IMG GPRs in achieving success. Local strategic examination support, such as the KSS Curriculum and AKT Support for Training (CAST) programme can facilitate the application of this model. Recommendations include early discussions on differential attainment, the development of a comprehensive AKT program, and tailored educational interventions. The study also recommends further research across diverse training regions to refine educational strategies and ensure equitable opportunities.}, } @article {pmid40658360, year = {2025}, author = {Ali, F and Malak, A and Wazir, S and Fakhar, A and Jawad, M}, title = {A Ring‑augmented Roux‑en‑Y Gastric Bypass with MiniMizer Ring is Effective and Safe in Patients with a BMI > 50 kg/m[2].}, journal = {Obesity surgery}, volume = {}, number = {}, pages = {}, pmid = {40658360}, issn = {1708-0428}, abstract = {This Letter to the Editor evaluates Jense et al.'s (2025) study on MiniMizer ring-augmented Roux-en-Y gastric bypass (RYGB) for patients with BMI > 50 kg/m[2]. While the study demonstrates promising outcomes-35.2% total weight loss (TWL) at 2 years and 83.3% diabetes remission-several limitations warrant discussion. Key concerns include (1) the absence of stratified data on ring diameters (6.5-8.0 cm), which obscures optimal size selection for balancing efficacy and complication risks; (2) limited applicability to revisional surgery, a common need for super-obese patients; and (3) insufficient reporting of micronutrient deficiencies and quality-of-life impacts, critical for holistic patient care. Additionally, the lack of cost-effectiveness analysis leaves the MiniMizer ring's economic justification unclear. We commend the authors' rigorous methodology but propose future research to address these gaps through standardized ring sizing, inclusion of revisional cases, and comprehensive nutritional and economic evaluations. These refinements would enhance the evidence base for ring-augmented RYGB in high-risk populations.}, } @article {pmid40658147, year = {2025}, author = {Ramzan, H and Saeed, I and Naveed, H}, title = {Comments on investigating leucine-enriched branched-chain amino acid (BCAA) supplementation in elderly chronic kidney disease (CKD) patients.}, journal = {International urology and nephrology}, volume = {}, number = {}, pages = {}, pmid = {40658147}, issn = {1573-2584}, abstract = {We comment on Sunsandee et al.'s RCT of leucine-enriched BCAA supplementation in elderly CKD patients. Despite a modest muscle gain, methodological and practical limitations-including unbalanced BCAA formulation, insensitive functional tests, lack of subgroup analysis, and high pill burden-undermine generalizability. Recommendations for future studies are discussed.}, } @article {pmid40654711, year = {2025}, author = {Major, AJ and Abdaltawab, A and Phillips, JM and Wang, T and Lee, EK and Lichtenfeld, MJ and Chandrasekaran, C and Saalmann, YB and Maier, A and Desimone, R and Miller, EK and Bastos, AM and Mendoza-Halliday, D}, title = {A ubiquitous spectrolaminar motif across independent studies, including Mackey et al.'s own data.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {40654711}, issn = {2692-8205}, abstract = {Our study (Mendoza-Halliday et al., 2024) made two contributions: (1) discovery of a ubiquitous cortical motif and (2) a tool derived from it-the Frequency-based Layer Identification Procedure (FLIP and vFLIP). Mackey et al. critique the tool, questioning its advantage over classic current source density (CSD) analysis, and reason backwards to challenge the motif's ubiquity. In our rebuttal, we confirm the spectrolaminar motif in diverse cortical areas using data from multiple research groups (who joined us in this rebuttal) as well as Mackey et al.'s own dataset. Additionally, we introduce vFLIP2, an improved version of our tool that addresses their comments. It reliably identified and localized the motif in our data and Mackey et al.'s data. Our findings reaffirm the motif's ubiquity. We value Mackey et al.'s comments, which helped refine our tool.}, } @article {pmid40653853, year = {2025}, author = {Vejlgaard, E and Langberg, C and Jervelund, SS and Øverup, CS}, title = {Experiences of Female Victims of Intimate Partner Violence Accessing Support Services in Denmark.}, journal = {Violence against women}, volume = {}, number = {}, pages = {10778012251356958}, doi = {10.1177/10778012251356958}, pmid = {40653853}, issn = {1552-8448}, abstract = {This study examined how female victims of intimate partner violence (IPV) in Denmark experience access to support services within the social and healthcare systems. Semistructured interviews were conducted with 10 women. Although women faced significant barriers to assistance, they were aided by their social networks. Societal perceptions on IPV, especially psychological violence, and frontline personnel's lack of expertise impeded their help-seeking behavior. We propose an adapted version of the Levesque et al.'s (2013) framework of access to this context. Addressing the barriers requires upskilling frontline personnel, delineation of responsibilities, and improved cross-sector collaboration.}, } @article {pmid40653468, year = {2025}, author = {Liu, Z and Sun, L and Gao, N and Li, W and Pang, L}, title = {Reciprocal regulation of GPNMB/HIF-1α for Inhibition of neuronal ferroptosis in delayed encephalopathy after acute carbon monoxide poisoning.}, journal = {Acta neuropathologica communications}, volume = {13}, number = {1}, pages = {154}, pmid = {40653468}, issn = {2051-5960}, support = {JJKH20231233KJ//Jilin Provincial Education Department/ ; Z2023LJL001//Tianhua Health Foundation of Jilin Province/ ; 82372211//National Natural Science Foundation of China/ ; }, mesh = {Animals ; *Ferroptosis/physiology/drug effects ; Rats ; *Hypoxia-Inducible Factor 1, alpha Subunit/metabolism ; *Carbon Monoxide Poisoning/metabolism/complications ; Male ; Rats, Sprague-Dawley ; *Neurons/metabolism/pathology ; *Membrane Glycoproteins/metabolism ; PC12 Cells ; *Brain Diseases/metabolism/etiology/pathology ; Oxidative Stress/physiology/drug effects ; }, abstract = {Delayed encephalopathy after acute carbon monoxide poisoning (DEACMP) is the most common complication after acute carbon monoxide (CO) poisoning. However, the pathogenesis of DEACMP remains ambiguous. The neuroprotective role of GPNMB has been observed in amyotrophic lateral sclerosis and Parkinson's disease. GPNMB was elevated in the brain tissues of DEACMP rats, while its function in DEACMP remains unclear. In this study, a CO poisoning rat model and oxygen-glucose deprivation (OGD)-treated PC-12 cells were established as an in vivo and in vitro DEACMP model, respectively. The ferroptosis inhibitor Ferrostatin-1 (Fer-1) ameliorated cognitive impairment, inflammation and oxidative stress of rats with DEACMP as assessed by Morris Water Maze test, ELISA assay and commercial kits of oxidative markers. Immunofluorescence, qRT-PCR or western blot showed that GPNMB was elevated in CA1 hippocampal tissues of CO-poisoned rats. Additionally, TUNEL staining, ELISA assay and western blot revealed that GPNMB rescued OGD-induced cell apoptosis, inflammation and ferroptosis in PC-12 cells. Mechanistical study showed that STAT3 was a transcriptional activator of GPNMB as detected by luciferase and ChIP assays, and co-immunoprecipitation and immunofluorescence staining revealed that GPNMB stabilized HIF-1α by direct binding. Functionally, GPNMB protected against OGD-induced impairments via inducing HIF-1α. Furthermore, GPNMB attenuated cognitive impairment, oxidative stress and neuronal ferroptosis of rats with DEACMP. In conclusion, GPNMB/HIF-1α exhibited neuroprotective effects via suppressing ferroptosis in DEACMP.}, } @article {pmid40651199, year = {2025}, author = {Carvalho, FR and Gavaia, PJ}, title = {Letter to the Editor: Robustness of osteoporosis risk prediction models with enhanced statistical analyses.}, journal = {Computers in biology and medicine}, volume = {196}, number = {Pt A}, pages = {110711}, doi = {10.1016/j.compbiomed.2025.110711}, pmid = {40651199}, issn = {1879-0534}, mesh = {Humans ; *Osteoporosis/epidemiology ; Female ; Male ; *Models, Statistical ; Middle Aged ; Risk Assessment ; Risk Factors ; Aged ; Adult ; Nutrition Surveys ; }, abstract = {In response to Oka et al.'s letter, we conducted additional statistical analyses to validate the robustness of our osteoporosis risk prediction model using NHANES 2007-2014 data (n = 7924). We evaluated 10 key predictors through Spearman's rho, Kendall's tau, Mutual Information (MI), and Total Correlation. Weight (BMX_BMXWT) and arm circumference (BMX_BMXARMC) showed strong negative correlations with osteoporosis risk (rho: 0.49, -0.47, p < 1e-270; MI: 0.17, 0.15), while age (DEMO_RIDAGEYR) exhibited a positive correlation (rho: 0.33, p < 1e-128; MI: 0.08). Total Correlation (32.68) confirmed significant multivariate interactions among predictors. These findings reinforce the model's predictive strength, addressing Oka et al.'s recommendations and affirming the importance of anthropometric and demographic factors in osteoporosis risk assessment.}, } @article {pmid40648551, year = {2025}, author = {Al-Ajlouni, YA and Al Ta'ani, O and Zweig, SA and Bak, M and Tanashat, M and Gabr, A and Khamis, Z and Al-Bitar, F and Islam, M}, title = {Assessing the Therapeutic Role of Rehabilitation Programs in Chemotherapy-Induced Peripheral Neuropathy (CIPN)-A Scoping Review.}, journal = {Healthcare (Basel, Switzerland)}, volume = {13}, number = {13}, pages = {}, pmid = {40648551}, issn = {2227-9032}, abstract = {Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a common, debilitating side effect of cancer treatment. Characterized by symptoms like pain, numbness, and muscle weakness, CIPN significantly impacts patients' quality of life. Current management strategies vary, with limited consensus on effective treatments. This scoping review aims to explore comprehensive rehabilitation interventions for CIPN, focusing on enhancing patient well-being and functional abilities. Methods: A scoping review, guided by Arksey and O'Malley's framework and Levac et al.'s refinements, was conducted to assess rehabilitation programs for CIPN. Searches across six databases were performed, with inclusion and exclusion criteria focusing on studies with physical rehabilitation interventions. Data were charted, detailing interventions, demographics, and outcomes. Results were synthesized descriptively and presented narratively with tables. Results: The review included 24 studies covering diverse cancer types and treatments, involving a total of 1167 participants. Various interventions for CIPN were assessed, and results were thematically categorized according to exercise category. Physical modalities like ultrasound and exercise showed promise in symptom relief for colorectal and breast cancer patients. No distinct advantage was found in the timing of exercise interventions. Complementary therapies such as acupuncture and yoga demonstrated effectiveness in managing CIPN symptoms. Conclusions: This review highlights the effectiveness of diverse physical and complementary interventions in managing CIPN, advocating for their integration into standard protocols. It emphasizes the need for holistic, patient-centered approaches that combine exercises, physical therapy, and complementary therapies to improve patient outcomes. These findings set a direction for future research and clinical practices focused on comprehensive and personalized CIPN management strategies.}, } @article {pmid40646421, year = {2025}, author = {McCormick, CR and Christie, J}, title = {Assessing Posner's theory of alerting: A meta-analysis of speed-accuracy effects.}, journal = {Attention, perception & psychophysics}, volume = {87}, number = {6}, pages = {2007-2028}, pmid = {40646421}, issn = {1943-393X}, mesh = {Humans ; *Reaction Time ; *Attention ; *Pattern Recognition, Visual ; *Psychological Theory ; *Orientation ; Cues ; Psychomotor Performance ; Discrimination, Psychological ; }, abstract = {Posner and his colleagues proposed a seminal theory of how alerting influenced information processing over 50 years ago (Posner et al., Memory & Cognition, 1, 2-12, 1973). In this study, participants were presented with warning signals at varying intervals before a target, and participants were asked to produce a spatial discrimination response. Trials in which participants were played a warning signal were compared to trials without a warning signal to understand the effect of phasic alerting using reaction time (RT) and error rate (ER). Posner and colleagues observed a general speed-accuracy trade-off (SAT) across conditions, in which faster RTs led to higher ER, and concluded that phasic alertness shifts response criteria without improving the efficiency of information processing. More recent research has questioned whether this theory of alerting applies generally across all time-courses and conditions. The current meta-analysis aimed to test Posner's theory of alerting (1975) using all available data in the field that closely matches the methodology used in Posner et al.'s Memory & Cognition, 1, 2-12, (1973) influential study. After including data from 16 published experiments across three different signal-target foreperiod durations, our conclusions support that while a speed-accuracy trade-off is likely present at shorter foreperiods (50 ms), the longer foreperiods (200 and 400 ms) show evidence of an increase in the rate of information processing when the participant was alerted.}, } @article {pmid40642997, year = {2025}, author = {Gordon, AD}, title = {Sexual Size Dimorphism in Australopithecus: Postcranial Dimorphism Differs Significantly Among Australopithecus afarensis, A. africanus, and Modern Humans Despite Low-Power Resampling Analyses.}, journal = {American journal of biological anthropology}, volume = {187}, number = {3}, pages = {e70093}, doi = {10.1002/ajpa.70093}, pmid = {40642997}, issn = {2692-7691}, support = {//Institute of Advanced Study, Durham University/ ; }, mesh = {Animals ; *Hominidae/anatomy & histology ; Humans ; Male ; Female ; Fossils ; *Sex Characteristics ; Pan troglodytes/anatomy & histology ; Anthropology, Physical ; Body Size ; }, abstract = {OBJECTIVES: Dimorphism estimates are used to infer competition levels, social structure, and mating system in fossil hominins. However, previous studies have reached conflicting conclusions about the degree of postcranial dimorphism present in Australopithecus afarensis, and statistical comparisons of postcranial size dimorphism between A. afarensis and other early hominins are lacking. This study addresses reasons for differences in published studies and directly compares dimorphism in A. afarensis, A. africanus, and extant hominids.

MATERIALS AND METHODS: Eight postcranial variables represent size for three extant hominids (gorillas, humans, and chimpanzees) and two extinct hominins (Australopithecus afarensis and A. africanus). A modified version of Gordon et al.'s (2008) geometric mean method is used to perform significance tests for direct comparisons of estimated sexual size dimorphism in two fossil samples with different patterns of missing data.

RESULTS: Both Australopithecus species are highly dimorphic-significantly more dimorphic than chimpanzees and modern humans. A. afarensis is also significantly more dimorphic than A. africanus.

DISCUSSION: Previous studies (and this analysis) are typically too low-powered to find significant differences between humans and extant African apes when sampled in the same manner as fossils, rendering negative results for fossil comparisons noninformative. In this study, effect sizes for differences in dimorphism between fossils and other species are large enough to be significant, even at low power. Results suggest intense sexual selection maintained high dimorphism in both fossil species, but also that different species-specific suites of selection pressure produced diversity in the degree of dimorphism present across Australopithecus species.}, } @article {pmid40640475, year = {2025}, author = {Heydari, K and Enichen, EJ and Li, B and Kvedar, JC}, title = {Leveraging retinal vascular features in non-invasive, early diagnosis of preeclampsia.}, journal = {NPJ digital medicine}, volume = {8}, number = {1}, pages = {422}, pmid = {40640475}, issn = {2398-6352}, abstract = {Wu et al.’s recent article, “Noninvasive early prediction of preeclampsia in pregnancy using retinal vascular features,” documents significant differences in retinal vascular features among women who develop preeclampsia and those with normotensive pregnancies. These findings provide evidence that retinal screening has the potential to be used as a low-cost, non-invasive screening strategy to support the earlier detection, prevention, and treatment of preeclampsia.}, } @article {pmid40640414, year = {2025}, author = {Pfaff, JAR}, title = {Commentary on Knapen et al.'s "Outcomes After Thrombectomy for Acute Ischemic Stroke Related to Type of Stent Retriever; a MR CLEAN Registry Study".}, journal = {Cardiovascular and interventional radiology}, volume = {48}, number = {8}, pages = {1140-1141}, pmid = {40640414}, issn = {1432-086X}, } @article {pmid40639550, year = {2025}, author = {Mondal, M and Chouksey, A and Gurjar, V and Tiwari, R and Srivasatava, RK and Mishra, PK}, title = {Micro(nano)plastics in the brain: Epigenetic perturbations in progression to neurodegenerative diseases.}, journal = {Neurotoxicology and teratology}, volume = {110}, number = {}, pages = {107521}, doi = {10.1016/j.ntt.2025.107521}, pmid = {40639550}, issn = {1872-9738}, abstract = {As global plastic production escalates, micro(nano)plastics (MNPs) have become pressing ecological and biomedical concerns. These pollutants are increasingly implicated in the pathogenesis of neurodegenerative diseases. Due to their nanoscale size and surface reactivity, MNPs can cross the blood-brain barrier, accumulating in neural tissues. Once internalized, they disrupt neuronal homeostasis by inducing oxidative stress, mitochondrial dysfunction, and chronic neuroinflammation, key processes in neurodegenerative progression. Mitochondria, central to neuronal energy and redox regulation, are particularly vulnerable, leading to impaired ATP production, elevated ROS, and pro-apoptotic signaling. Recent studies reveal that MNPs also induce epigenetic changes, including aberrant DNA methylation, histone modifications, and dysregulation of non-coding RNAs. These alterations can result in synaptic instability, persistent transcriptional reprogramming, and heightened susceptibility to diseases like Alzheimer's, Parkinson's, and amyotrophic lateral sclerosis. The mitochondrial epigenome is a vital target of MNP-induced disruption, offering potential biomarkers like methylated mtDNA and microRNAs for early diagnosis and prognosis. Understanding the molecular mechanisms behind these epigenetic alterations is essential for developing practical diagnostic tools and therapies. This review provides a comprehensive overview of MNP-induced neurodegeneration, focusing on mitochondrial and epigenetic disruptions. Moreover, it explores emerging biosensing technologies for detecting MNP-induced epigenetic alterations, highlighting the urgent need for further investigation to fully understand the neurotoxic potential of MNPs and develop preventive and therapeutic strategies for mitigating their effects on brain health.}, } @article {pmid40638257, year = {2025}, author = {Sadati, K and Mathieu, O and Cetrulo, CL and Lellouch, AG}, title = {Response to Letter: Sadati et al.'s "Anatomical Concerns and the Use of the Term Preservation in Referring to Procedures" A Scientific Defense of the Preservation Facelift Approach.}, journal = {Facial plastic surgery & aesthetic medicine}, volume = {}, number = {}, pages = {}, doi = {10.1177/26893614251358843}, pmid = {40638257}, issn = {2689-3622}, } @article {pmid40635292, year = {2025}, author = {Dartey, AF and Doe, TA and Klutsey, EE and Johnson, BB and Titiati, P and Agbalenyo, E and Otoo, A and Niebawiere, MD and Awuku, R and Ankomah, RA}, title = {A Qualitative Study of Community Health Nurses' Home Visiting Experiences in the Keta Municipality, Ghana.}, journal = {Journal of community health nursing}, volume = {}, number = {}, pages = {1-12}, doi = {10.1080/07370016.2025.2527657}, pmid = {40635292}, issn = {1532-7655}, abstract = {PURPOSE: This study explored the experiences of Community Health Nurses (CHNs) providing home-based services in the Keta Municipality, Ghana, emphasizing the challenges and barriers faced while delivering healthcare in remote and riverine communities.

DESIGN: An exploratory qualitative research approach was used to gain in-depth insights into CHNs' home visiting experiences within this specific context.

METHODS: Fifteen CHNs were purposively selected and interviewed using a semi-structured guide. The interviews were audio-recorded, transcribed, and thematically analyzed following Braun et al.'s six-step process to identify key themes and subthemes.

FINDINGS: Three themes with 12 subthemes emerged: (1) factors influencing the accessibility and frequency of home visits, (2) healthcare services provided during home visits, and (3) barriers to effective service delivery. The findings highlight geographical isolation, financial constraints, inadequate transportation, cultural barriers, and limited logistical resources as major challenges. Despite these, CHNs provide critical services, including antenatal and postnatal care, immunizations, health education, and health monitoring, to improve access to healthcare in underserved areas.

CONCLUSIONS: Home visiting is an essential healthcare delivery approach in Keta Municipality, serving as a bridge to healthcare for remote populations. Enhancing logistical support, addressing staffing shortages, and providing adequate incentives can significantly improve service delivery and healthcare outcomes.

CLINICAL EVIDENCE: The study underscores the importance of community-level interventions and policy support in optimizing healthcare delivery in rural and riverine communities, thereby improving maternal and child health and reducing healthcare inequities.}, } @article {pmid40634246, year = {2025}, author = {Uhrenfeldt, L and Galvin, K and Lorenzen, MD and Martinsen, B and Stie, M}, title = {Clinical Practice Based on Theory: Reflections on Mudd et al.'s Review for Excellence in Nursing.}, journal = {Journal of clinical nursing}, volume = {34}, number = {8}, pages = {3047-3050}, doi = {10.1111/jocn.70028}, pmid = {40634246}, issn = {1365-2702}, } @article {pmid40633015, year = {2025}, author = {Bandari, M and Osei, C and Bandari, M}, title = {Silent struggles: ADHD and anxiety during campus isolation.}, journal = {Journal of American college health : J of ACH}, volume = {}, number = {}, pages = {1-2}, doi = {10.1080/07448481.2025.2468836}, pmid = {40633015}, issn = {1940-3208}, abstract = {Building on Seddio et al.'s study of ADHD symptoms, anxiety, and internalizing behaviors among college students during COVID-19, we identify key methodological limitations and propose refinements. The study's cross-sectional design, small sample size (n=200) from a single northeastern institution, high ADHD prevalence (35%), gender imbalance (82.1% female), reliance on self-report measures, and lack of ADHD subtype differentiation limit its generalizability and clinical applicability. We recommend standardized mental health screenings for internalizing behaviors, integrated care pathways within student health services, and faculty training to recognize subtle signs of distress. Future research should adopt longitudinal designs with multi-institutional cohorts, control groups, and diverse demographics to better understand comorbid ADHD and anxiety during acute stress. These improvements would strengthen the evidence base for supporting collegiate mental health.}, } @article {pmid40632124, year = {2025}, author = {Boretti, A}, title = {Constructing Risk Ethically: A Normative Extension of Clark et al.'s "Risk-Making" Theory for Disorders of Consciousness.}, journal = {AJOB neuroscience}, volume = {16}, number = {3}, pages = {149-152}, doi = {10.1080/21507740.2025.2519433}, pmid = {40632124}, issn = {2150-7759}, } @article {pmid40631648, year = {2025}, author = {Brand, M}, title = {Cultural Considerations in the Context of the I-PACE Model of Addictive Behaviors: Commentary on Lee et al.'s "Applying the Interaction of Person-Affect-Cognition-Execution Model to Addictive Behaviors in East Asian Countries: Feasibility and Considerations".}, journal = {Journal of the Korean Academy of Child and Adolescent Psychiatry}, volume = {36}, number = {3}, pages = {172-173}, pmid = {40631648}, issn = {2233-9183}, } @article {pmid40631493, year = {2025}, author = {Li, W and Gillies, RM and Sun, H and Khan, A}, title = {Career indecision among medical students: A scoping review of contributing sources, associated factors, and support strategies.}, journal = {Medical teacher}, volume = {}, number = {}, pages = {1-19}, doi = {10.1080/0142159X.2025.2520927}, pmid = {40631493}, issn = {1466-187X}, abstract = {BACKGROUND: While career indecision is well-studied in vocational psychology, its application in medical education remains limited. This scoping review examined sources of indecision, associated factors, and strategies to support medical students' career decision-making.

METHODS: A systematic search of PubMed, Scopus, CINAHL, and ERIC identified relevant studies published from January 2014 to December 2024. Two reviewers independently screened articles and data were charted. Eligible articles were synthesised using directed qualitative content analysis with inductive expansion, guided by Kulcsár et al.'s career decision-making taxonomy.

RESULTS: Ninety-three studies were included. Most studies focused on the career aspect of specialty selection. Career decision-making difficulties were categorised into Readiness (dysfunctional beliefs, career decision-making self-efficacy, willingness, general indecisiveness), Lack of Information (about self, about world of work, about how to make career decisions) and Use of Information (unreliable information, internal conflicts, external conflicts). Personal coping strategies and institutional support recommendations were identified. Influencing factors included demographics, personal traits, educational experiences, attitudes, and macro-level disruptions.

CONCLUSIONS: This review maps medical students' career decision-making difficulties to a structured framework and outlines support strategies and influencing factors. Findings underscore the value of integrating career psychology into medical education and addressing structural barriers to better support students' career development.}, } @article {pmid40629221, year = {2025}, author = {Maheux-Caron, V and Hétu, S and Saleh, G and Rigoulot, S and Gamache, D}, title = {Empathy in dark and vulnerable personality traits: a multimethod study from self-reported, performance-based, and electrophysiological empathy correlates.}, journal = {Cognitive, affective & behavioral neuroscience}, volume = {}, number = {}, pages = {}, pmid = {40629221}, issn = {1531-135X}, support = {BESC M//Social Sciences and Humanities Research Council of Canada/ ; 261746//Fonds de Recherche du Québec - Santé/ ; 282269//Fonds de Recherche du Québec - Santé/ ; 35450//Quebec Bio-imaging Network/Fonds de recherche du Québec - Santé (FRQS): Réseaux de recherche thématiques/ ; 285259//Fonds de Recherche du Québec-Société et Culture/ ; ES D3 - 559180 - 2021//Natural Sciences and Engineering Research Council of Canada/ ; RGPIN-2020-06706//Natural Sciences and Engineering Research Council of Canada/ ; }, abstract = {Deficits in empathic functioning are a hallmark of dark personality traits, such as psychopathy, narcissism, Machiavellianism, and sadism, which form the Dark Tetrad construct (D4). The Vulnerable Dark Triad construct (VDT; borderline symptomatology, vulnerable narcissism, and secondary psychopathy) shares antagonism with the D4 but also includes emotionally vulnerable facets. Maheux-Caron et al. (2024) uncovered meaningful profiles based on D4 and VDT traits using Latent Class Analysis and found significant differences across profiles on self-reported empathy. The current study aimed to investigate differences in empathy and emotional face processing across profiles from Maheux-Caron et al.'s (2024) work-adopting a multimethod approach in which dispositional, behavioral, and electrophysiological empathy correlates were examined. An empathy task based on the Affective and Cognitive Measure of Empathy (ACME; Vachon & Lynam, 2016) was developed and preliminary construct validity data for the task are reported in the present paper. Significant differences were found across profiles on dispositional affective empathy and behavioral cognitive empathy. Although differences across profiles on electrophysiological data were not found, exploratory supplemental analyses showed associations between the personality measures of borderline and Machiavellian traits and a reduced N170 amplitude. The present study highlights how the operationalization of empathy and its related measures play a paramount role in understanding empathic functioning. Our findings support the idea that self-reported cognitive empathy measures are not valid proxies for actual empathic ability, and this should be carefully considered in research and clinical practice settings.}, } @article {pmid40628227, year = {2025}, author = {Chang, S and Jiang, R and Cao, Y and Pearson, J and Meng, M}, title = {Reply to Scholz et al.}, journal = {Current biology : CB}, volume = {35}, number = {13}, pages = {R647-R648}, doi = {10.1016/j.cub.2025.05.010}, pmid = {40628227}, issn = {1879-0445}, mesh = {Humans ; *Imagination/physiology ; *Visual Cortex/physiology/physiopathology ; *Visual Perception/physiology ; }, abstract = {In our recent study[1], we investigated the neural basis of attempts at forming voluntary visual imagery in individuals with aphantasia and found that although these individuals lack visual imagery experience, their early visual cortex exhibits stable, content-specific activation patterns during imagery attempts. Unlike in the neurotypicals, these neural representations, however, differ from those evoked during perception, as indicated by the failure of cross-decoding between imagery and perceptual tasks. In this response, we address Scholz et al.'s commentary[2] on our findings and the broader implications for theories of unconscious imagery, emphasizing that while we do not claim the presence of unconscious imagery, our results suggest that early visual activity in aphantasia may reflect perceptual-like, but transformed or non-conscious, representations.}, } @article {pmid40626040, year = {2024}, author = {Shifrer, D and Pappas Fly, S and Springer, R and Dinh, X}, title = {School-based health centers and mental health stigma before and during the pandemic.}, journal = {SSM. Qualitative research in health}, volume = {6}, number = {}, pages = {}, pmid = {40626040}, issn = {2667-3215}, support = {UL1 GM118964/GM/NIGMS NIH HHS/United States ; }, abstract = {The mental health of children, and especially adolescents, has been a global public health priority for decades. School-based health centers (SBHCs) are health clinics established in close proximity to elementary and secondary schools for the purpose of increasing access to medical, and particularly mental health services, for children and adolescents. Yet, like other health clinics, SBHCs struggle to overcome structural and interpersonal stigma related to mental health conditions and support. Then, the pandemic threatened the sustainability and efficacy of SBHCs just as youth's mental health needs skyrocketed. We use Stangl et al.'s (2019)framework for health-related stigma to analyze data from 36 interviews with SBHC Coordinators in Oregon and their Educator Partners to investigate: 1) What implications does mental health-related stigma have for SBHCs' delivery of mental health services to children and adolescents? 2) How did these factors change during the pandemic? Consistent with Stangl et al.'s (2019) framework for health-related stigma, mental-health-related stigma is evident in this study in terms of the secondary stigma youth are reported to experience from peers and families in terms of visiting a SBHC for mental health services, as well as in limitations in the quantity and quality of resources dedicated to providing mental health services. The pandemic had contradictory effects, both increasing and reducing stigma along two axes: cultural perceptions of mental health problems and telehealth.}, } @article {pmid40618132, year = {2025}, author = {Oliver, N and Twentyman, K and Howie, K}, title = {'Everybody's voice is important': using translational simulation as a component of change management.}, journal = {Advances in simulation (London, England)}, volume = {10}, number = {1}, pages = {38}, pmid = {40618132}, issn = {2059-0628}, abstract = {BACKGROUND: Changes in healthcare systems are often highly stressful experiences for healthcare teams, contributing to disengagement and resistance to change. Translational simulation has been shown to be impactful at both organisational and department-based levels; however, its impact on the experience of change for frontline staff has not, to date, been explicitly explored. Understanding the impact of translational simulation on the perception of teams exposed to healthcare system changes, and how to optimise our approaches to support change management on a team and individual level, may be the difference between an overwhelmed and disengaged workforce and a positive and engaged one.

METHODS: We used template analysis as an analytic tool to gain new understanding of the impact of translational simulation on the experiences of staff members undergoing change. Utilising Bartunek et al.'s (2006) conceptual framework to inform the priori themes of our template, we interviewed nine Registered Nurses involved in a major relocation into a purpose-built paediatric hospital in Edinburgh, UK. We sequenced the interviews to take place in the lead up to a planned simulation event, with a follow up second interview 1 month after the hospital move. On the day of the simulation, we additionally collected a series of 'headline' thoughts from the group across the simulation to track their thoughts and feelings toward the move. Interviews and 'headlines' were recorded, transcribed, and thematically analysed using template analysis methods.

RESULTS: Our findings demonstrate that the use of translational simulation significantly enhanced staff preparedness and engagement during a major hospital relocation, suggesting that incorporating such approaches can be a valuable component of change management strategies in healthcare settings.

CONCLUSIONS: Whilst further research is required, these findings promote the considered use of translational simulation as a potentially significant component of the change management process.}, } @article {pmid40616625, year = {2025}, author = {Chen, J and Zhao, H}, title = {Critical Insights On Enhancing Patient-centered Care to Improve Multivitamin Adherence After Bariatric Surgery: A Response to van Es et al.'s Observational Study.}, journal = {Obesity surgery}, volume = {}, number = {}, pages = {}, pmid = {40616625}, issn = {1708-0428}, abstract = {This letter addresses the study by van Es et al. on multivitamin adherence after bariatric surgery and the implementation of patient-centered care (PCC) by healthcare professionals (HCPs). The authors commend the study's efforts to advance PCC but offer critical insights into the limitations of its methodology. The letter highlights the need for a more nuanced understanding of how different healthcare providers apply PCC, the potential biases introduced by the knowledge of observation, and the subjectivity inherent in the observational data collection method. The authors suggest that incorporating patient feedback and using a more objective approach could improve the study's conclusions. Overall, the letter calls for further improvements in PCC practices and research on multivitamin adherence after bariatric surgery.}, } @article {pmid40616054, year = {2025}, author = {Jacobs, I and Vanden Bossche, D and Willems, S and Vanthomme, K}, title = {Understanding the profile of community health workers in breast cancer screening education: women's preferences and insights from a qualitative focus group study.}, journal = {International journal for equity in health}, volume = {24}, number = {1}, pages = {193}, pmid = {40616054}, issn = {1475-9276}, support = {CPR- 2022/1887c//Stichting Tegen Kanker/ ; }, abstract = {BACKGROUND: Despite efforts to reduce disparities in breast cancer screening uptake in Flanders, certain population groups, such as women with a lower income, a lower educational attainment, women living further from screening units, and with a migration background, remain less likely to participate in the population-based mammography screening program. Community Health Workers (CHWs) are effectively involved in breast cancer screening programs in various countries to reach underserved women. In Flanders, Belgium, the involvement of CHWs in breast cancer screening programs is relatively recent. However, little is known about the preferences of the target population regarding the potential profile of a CHW in breast cancer screening education in Flanders. This study aims to explore this gap.

METHODS: Four focus group discussions were conducted between August and December 2023. Data were analysed using Qualitative Content Analysis to identify key categories, which were subsequently organized according to Kok et al.’s framework of CHW performance.

RESULTS: The results emphasize the importance of the desired competencies of CHWs, including professional knowledge and expertise, personal experience in shaping competencies, effective communication skills, cultural awareness and motivational and supportive competencies. Empathy, sociability, and adaptability were identified as key attitudes for fostering trust and creating supportive relationships. Trust emerged as a central theme, where female CHWs were preferred for their ability to enhance safety and trust, especially when they had prior experience with breast cancer screening.

CONCLUSION: The findings of this study provide actionable insights regarding the profile of CHWs involved in breast cancer screening education, underscoring the need for a balanced combination of attributes to address the specific preferences of the target population. By integrating the target populations’ perspectives, this research bridges gaps in existing CHW performance frameworks, offering a more comprehensive understanding of CHW performance. Recruiting CHWs with the right combination of competencies, interpersonal skills and attitudes is critical for the success of breast cancer education programs. Further research is needed to explore these findings in other contexts.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12939-025-02508-0.}, } @article {pmid40615730, year = {2025}, author = {Hoos, O and Gronwald, T}, title = {Detrended fluctuation analysis of heart rate variability during exercise: Time to reconsider the theoretical and methodological background. Comment on: Cassirame et al.`s (2025) Detrended fluctuation analysis to determine physiologic thresholds, investigation and evidence from incremental cycling test. Eur J Appl Physiol 125:523-533.}, journal = {European journal of applied physiology}, volume = {}, number = {}, pages = {}, pmid = {40615730}, issn = {1439-6327}, } @article {pmid40604407, year = {2025}, author = {Goff, M and Hindi, A and Hammond, J and Jacobs, S}, title = {Access or continuity: a zero sum game? A systematic review of the literature examining the relationship between access and continuity in primary healthcare.}, journal = {BMC primary care}, volume = {26}, number = {1}, pages = {202}, pmid = {40604407}, issn = {2731-4553}, support = {Do the organisational and workforce developments associated with the introduction of primary care networks (PCNs) affect patients' experience of continuity of care?//Health Foundation/ ; Do the organisational and workforce developments associated with the introduction of primary care networks (PCNs) affect patients' experience of continuity of care?//Health Foundation/ ; Do the organisational and workforce developments associated with the introduction of primary care networks (PCNs) affect patients' experience of continuity of care?//Health Foundation/ ; Policy Research Unit in Health and Social Care Systems and Commissioning//National Institute for Health and Care Research/ ; }, mesh = {Humans ; *Continuity of Patient Care/organization & administration ; *Primary Health Care/organization & administration ; *Health Services Accessibility ; United Kingdom ; }, abstract = {BACKGROUND: In recent years there has been a policy drive in the UK to improve patients' access to appointments in primary care. However, the focus on timely access could undermine continuity of care. This paper aims to investigate how continuity of care and access to care are interrelated and their relative importance for patients and healthcare professionals.

METHODS: A systematic review was conducted using six academic databases (EMBASE, PubMed, Scopus, Web of Science, CINAHL and PsycINFO). Reference lists of included studies and Google Scholar were searched for additional papers. Included were peer-reviewed journal articles in English based on studies in primary care settings from any country, publication date and study design, based on data from any stakeholders. Conference abstracts, opinion papers, reports and literature reviews, studies in secondary or tertiary care or continuity between healthcare settings and studies about development of instruments to measure continuity of care or examining outcomes only were excluded. Fifty-six papers were identified for inclusion in the review. Studies presented differing perspectives on continuity and access, conceptualisations of access and continuity, and, measures used. We conducted thematic analysis of the literature and used Haggerty et al.'s (2003) conceptualization of continuity and Boyle et al.'s (2020) conceptualization of access to synthesise the data.

FINDINGS: Themes arising were: system-level, practice-level and patient-level factors that influence access and continuity of care, what is important to patients, and how providers can support access and continuity of care. We found that 'choice of access' has the strongest relationship with relational continuity, however, 'physical access', or the ability to get and 'attend' an appointment, supersedes other dimensions of access as necessary but not sufficient for continuity of care.

CONCLUSIONS: Our synthesis provides evidence that experiencing continuity depend on the combination of patients' demographic characteristics and health conditions, with situational circumstances, including characteristics of the health system and provider, which are more or less changeable. We propose a theoretical framing of the relationships between the dimensions of access and continuity. It can support policymakers and providers in understanding how to balance providing both access and continuity for patients.}, } @article {pmid40604073, year = {2025}, author = {Mahroos, F and Habiba, S and Lazreg, IK and Kanan, S and Samara, F}, title = {Characterization and health risk assessment of chemical and microbial pollutants in particulate matter from dust prone regions.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {23601}, pmid = {40604073}, issn = {2045-2322}, support = {Habiba_S_CAS-URG24//American University of Sharjah, United Arab Emirates/ ; Habiba_S_CAS-URG24//American University of Sharjah, United Arab Emirates/ ; Habiba_S_CAS-URG24//American University of Sharjah, United Arab Emirates/ ; FRG24-C-S30 (AS 1725)//American University of Sharjah/ ; FRG24-C-S30 (AS 1725)//American University of Sharjah/ ; }, mesh = {Risk Assessment ; *Particulate Matter/analysis ; *Dust/analysis ; Polycyclic Aromatic Hydrocarbons/analysis ; Humans ; Metals, Heavy/analysis ; *Air Pollutants/analysis ; Environmental Monitoring ; Bacteria/genetics/isolation & purification/classification ; }, abstract = {Increasing anthropogenic contributions to desert dust storms have raised significant public health concerns, particularly in arid/semi-arid regions. This study investigated particulate matter (PM) composition in an arid environment, focusing on organic, heavy metal, and microbial contaminants, along with comprehensive health risk assessments. ICP-OES analysis of inorganic matter showed moderate concentrations (> 8.21 µg/g) of Ca, Fe, Al, S, Mg, and Rb, while K, Cu, P, and Na were detected at low concentration levels, along with other trace metals. GC-MS analysis identified 11 targeted polycyclic aromatic hydrocarbons (PAHs), including phenanthrene, benzo[b]fluoranthene, and chrysene. Several organic pollutants, including some from the PFAS group, were detected in the samples. 16 S rRNA sequencing identified seven bacterial species, including Enterococcus faecium, Staphylococcus spp., and Acinetobacter radioresistens. Toxicity calculations indicated no significant lung cancer risk associated with PAHs, with further calculations suggesting minimal population-level risks. However, heavy metal risk metrics indicated greater non-carcinogenic risks than carcinogenic ones. The microbial species identified predominantly belonged to risk groups 1 and 2, representing opportunistic, infection-causing pathogens. This study highlights the necessity for a multidisciplinary approach to analyze complex dust particle constituents and their potential health impacts and calls for targeted air quality management policies to mitigate public health risks.}, } @article {pmid40600819, year = {2025}, author = {Sather, TW and Zorn, CR and Andersen, G}, title = {Mapping Primary Progressive Aphasia Best Practices to a Person-Centered Video Biopic.}, journal = {American journal of speech-language pathology}, volume = {}, number = {}, pages = {1-18}, doi = {10.1044/2025_AJSLP-24-00406}, pmid = {40600819}, issn = {1558-9110}, abstract = {PURPOSE: A stakeholder-engaged, collaboratively developed video biopic about the lived experience of primary progressive aphasia (PPA) was examined to assess its impact on graduate students' understanding of the lived experience of PPA and best practice principles in PPA.

METHOD: Using a post-then-pre-design, 22 graduate students were surveyed after watching the biopic regarding their understanding of the neurological aspects of PPA and the lived experience of PPA. Additionally, they mapped the presence of Volkmer et al.'s (2023) PPA best practice principles within the biopic. Quantitative measures of central tendency, as well as qualitative measures, were used to analyze the data. Reflexive thematic analysis was used to identify themes related to understanding of the neurological and lived experience components of PPA prior to and after watching the biopic.

RESULTS: After viewing the biopic, participants identified significant changes in understanding both the neurological aspects of PPA and the lived experience of PPA. However, their reported understanding of the lived experience of PPA was more influenced, impactful, and relevant than the changes in their understanding of the neurological aspects. Students identified occurrence of all seven PPA best practice principles within the biopic.

CONCLUSIONS: Students reported significant changes in understanding prior to and following viewing the biopic. Video biopics may be an effective tool to support increased understanding of the lived experience of conditions, including PPA, and support increased awareness and application of evidence-based practices.}, } @article {pmid40589838, year = {2024}, author = {Pourkhalili, S and Soltani Shal, R and Abolghasemi, A and Dianatkhah, M and Gharipour, M}, title = {Estimating the Heritability of Hoarding Symptoms: Insights from a Classical Twin Study "New Insights on the Nature of Clutter".}, journal = {Iranian journal of psychiatry}, volume = {19}, number = {4}, pages = {424-430}, pmid = {40589838}, issn = {1735-4587}, abstract = {Objective: Hoarding disorder is a complex condition that significantly impacts individuals' lives, characterized by excessive acquiring, difficulty discarding, clutter, distress, and impairment. This study aimed to examine the extent to which genetics and environment influence difficulty discarding, excessive acquisition, and clutter through the implementation of a classical twin study. Method : This classical twin study, conducted between April and September 2021, enrolled 194 twins (97 pairs) from Isfahan, recruited through the Isfahan Twins Registry (ITR). A total of 194 twins, consisting of 100 monozygotic (MZ) and 94 dizygotic (DZ) twins, participated in this study. Participants aged 16-50 were invited electronically and completed an online consent form and questionnaire. Hoarding symptoms were assessed using the saving inventory-revised. Zygosity was determined using a self-report method based on Song et al.'s questionnaire. To estimate the heritability of hoarding symptoms, the classical univariate twin model was employed. Results: Based on the univariate analysis, the heritability estimates for difficulty discarding and excessive acquisition were found to be 0.43 and 0.52, respectively. However, the results did not provide support for the role of genetics in clutter. Instead, it was indicated that the common environment accounted for 0.54 of the variance in clutter, while the specific environment contributed 0.46 to this symptom. Conclusion: The difficulty discarding and excessive acquisition were found to be moderately heritable. On the other hand, considering the contribution of genetics and environment to clutter, the results raise doubts about the association of clutter with hoarding. The relatively low genetic influence suggests that this trait may overlap with other behaviors rather than hoarding.}, } @article {pmid40585776, year = {2025}, author = {Brisson, R}, title = {Bullying Trends or Definitional Drift? A Methodological Critique of Molcho et al.'s Study.}, journal = {International journal of public health}, volume = {70}, number = {}, pages = {1608711}, pmid = {40585776}, issn = {1661-8564}, } @article {pmid40585668, year = {2025}, author = {Kunhikannan, A and Suresh, TN and Mohiyuddin, SMA}, title = {A Study on Cancer-Associated Fibroblast Using Alpha-Smooth Muscle Actin Immunohistochemistry in Oral Squamous Cell Carcinoma.}, journal = {Cureus}, volume = {17}, number = {5}, pages = {e85027}, pmid = {40585668}, issn = {2168-8184}, abstract = {Background Oral squamous cell carcinoma (OSCC) represents a significant global health burden with complex pathophysiology involving tumor microenvironment interactions. The tumor stroma, particularly cancer-associated fibroblasts (CAFs), plays a crucial role in tumor advancement, invasion, and metastasis. CAFs, identified by alpha-smooth muscle actin (α-SMA) expression, influence tumor behavior through extracellular matrix remodelling and pro-tumorigenic signalling. Despite emerging evidence of their prognostic significance, the relationship between CAF expression patterns and clinicopathological parameters in OSCC remains inadequately characterized. Objectives This study aimed to detect CAFs using α-SMA immunohistochemistry in OSCC and evaluate their association with LNM and pTNM staging, potentially identifying new prognostic markers for clinical management. Methodology This laboratory-based analytical study was conducted between September 2022 and December 2023. Histopathologically confirmed OSCC cases (n=88) treated by composite resection and cervical lymph node dissection were included, excluding recurrent cases, patients who received neoadjuvant chemotherapy, and second primary cancers. H&E slides were reviewed for LNM and pTNM staging. Immunohistochemical staining for α-SMA was performed on 4 μm formalin-fixed paraffin-embedded tissue sections using heat-induced antigen retrieval, followed by incubation with primary antibody and horseradish peroxidase (HRP)-conjugated secondary antibody. CAF expression was quantified using Kellermann et al.'s scoring system (Score 1 is <1%, Score 2 is between 1% and 50%, and Score 3 is >50% stained cells) and categorized by distribution pattern (focal, network, or spindle). Additional parameters assessed included tumor-stroma ratio (TSR), worst pattern of invasion (WPOI), tumor budding (TB), and tumor-infiltrating lymphocytes (TILs). Results The study population comprised 88 patients (69.3% female, 30.7% male) (average age: 56.97 years). The buccal mucosa represented the most frequent site (50%), with well-differentiated tumors predominating (80.7%). Pathological staging revealed Stage IVA as the most prevalent (33%), followed by Stage III (31.8%). Regarding CAF expression, Score 3 (abundant CAFs) was observed in 55.7% of cases, Score 2 in 40.9%, and Score 1 in only 3.4%. Network pattern CAF distribution predominated (38.6%), with equal representation of focal and spindle configurations (30.7% each). Statistical analysis revealed no significant association between CAF scores and LNM (p=0.758); however, CAF distribution patterns demonstrated a statistically significant association with pTNM staging (χ[2]=26.716; p=0.001), with advanced stages showing a distinct pattern shift toward network and spindle arrangements. Notably, significant correlations were observed between TSR and CAF score (p<0.0001), TB and CAF score (p=0.021), and TB and LNM (p=0.047). More aggressive invasion patterns demonstrated higher CAF scores and increased TB intensity. Conclusion While CAF scores alone did not predict LNM, CAF architectural patterns demonstrated significant associations with pathological staging in OSCC. The correlations between CAF expression, TB, and invasion patterns suggest that CAF distribution may serve as a valuable prognostic indicator. These findings highlight the potential of CAF architectural evaluation as an adjunctive histopathological parameter for risk stratification in OSCC patients.}, } @article {pmid40584275, year = {2025}, author = {Mishra, A and Kumar, G}, title = {Ligand-Receptor Analysis of Brain Cell Type Marker Data Reveals Intricate Endothelial Interaction.}, journal = {Annals of neurosciences}, volume = {}, number = {}, pages = {09727531251343254}, pmid = {40584275}, issn = {0972-7531}, abstract = {BACKGROUND: Brain endothelial interaction with neurons, astrocytes, oligodendrocytes and microglial cells is critical for brain physiology; it is still far from being mapped. Understanding of the endothelial communication with other brain cell type could unravel novel insight into neurovascular homeostasis.

PURPOSE: This study aims to construct neurovascular interaction network, focusing on brain endothelial cell interactome using brain cell marker gene dataset and ligand-receptor (LR) pair.

METHODS: We curated brain marker gene list from McKenzie et al.'s brain cell type top 1000 marker list of endothelial, microglia, astrocyte, neuron, oligodendrocyte and oligodendrocyte progenitor cell (OPC) and extracted LR interaction between them. Subsequently, using Cytoscape, endothelial cell interaction map was constructed and top interaction and hub gene were derived. Moreover, we performed Kyoto encyclopedia of genes and genomes (KEGG) pathways enrichment (p value < .1) to infer biological information hidden.

RESULTS: Neurovascular LR interaction showed endothelial cells as the top network having 25.34% of total interaction with 176 outgoing and 171 incoming interactions. A considerable portion of signalling (11%) is involved in autocrine signalling functionally related to vascular tone, angiogenesis and others. Paracrine signalling between endothelial cells with microglia, astrocytes, neurons and OPC constituted 13.5%, 8.9%, 5.8% and 4.9% of total interactions, respectively. Functional enrichment of LR interaction in endothelial-microglia, endothelial-astrocyte and endothelial-neuron networks constitutes 49, 45 and 36 significant KEGG pathways (p value < .1) respectively. These pathways include extracellular matrix (ECM) receptor, axon guidance, chemokine, nuclear factor kappa B (NF-kB) and signalling pathways, among others. Hub gene analysis showed ITGB1 in endothelial cells, ITGA4 in microglia, NOTCH2 in astrocytes and LAMC2 in neurons having maximum interaction in the endothelial network.

CONCLUSION: This study recapitulated not only previously known gene interactions using a markers gene list but also identified novel interactions between endothelial and other brain cell types. In conclusion, this analysis underscores the critical role of endothelial cell interactions in brain physiology.}, } @article {pmid40577943, year = {2025}, author = {Jain, NR}, title = {Haunted by ableism: Ghosts of the past, present, and future in medical education.}, journal = {Social science & medicine (1982)}, volume = {382}, number = {}, pages = {118321}, doi = {10.1016/j.socscimed.2025.118321}, pmid = {40577943}, issn = {1873-5347}, abstract = {Western medical education teaches a haunted curriculum of ableism. Bringing the hidden curriculum into conversation with hauntology and spectral studies, Ansari et al.'s haunted curriculum invites exploration of how professional education challenges and reproduces specters of injustice. I take Derrida's assertion that the specter brings together the past, present, and future and draw from critical disability theory to argue that medical education is haunted by three morphing ghosts that echo ableism through time. These ghosts illustrate medical education's imputation of bodymind hierarchies, attending to their violent effects towards disabled people as patients and as learners. Elimination/exclusion, the ghost of medicine's past, carries the memory of medical education's involvement in eugenics practices that removed disabled people from society, and its creation of technical standards that sought to exclude disabled people from medical education. Cure/inclusionism, the ghost of medical education's present, may appear more benign but rattles past ableism by perpetuating ideals of cure and maintaining rigid educational standards. Crip/transformation, the ghost of medical education's future, activates Kafer's politics of crip futurity through anti-ableist education and the stories of successful disabled physicians across time. These ghosts carry the possibility for a reckoning. I propose that medical education channel all three of these ghosts, feel the frictions of ableism past, present, and future, learn from them to resist further harm, and transform toward justice for learners and patients.}, } @article {pmid40572054, year = {2025}, author = {Arnahoutova, K and De Geest, S and Mielke, J and Boaz, A and Schoemans, H and Valenta, S}, title = {Exploring Stakeholder Involvement in Intervention Implementation Studies: Systematic Evidence Synthesis With an Evidence Gap Map Approach.}, journal = {Evaluation & the health professions}, volume = {}, number = {}, pages = {1632787251352837}, doi = {10.1177/01632787251352837}, pmid = {40572054}, issn = {1552-3918}, abstract = {Stakeholder involvement (SI) is essential for effective and sustainable intervention implementation, yet practical guidance is lacking. This study mapped SI use in implementation science studies, identified gaps, and proposed a practical framework for improved SI planning. Using an evidence gap map approach, this study built on Mielke et al.'s (2022) methodology, which identified implementation studies from 2015-2020. The search was updated to include studies from 2021-2023 from PubMed, using the same search strategy and inclusion criteria. Data extraction followed the Guidance for Reporting on Involvement of Patients and the Public reporting checklist. From 10,184 studies, a random sample of 2,005 was screened, adding 162 implementation science studies to Mielke et al.'s 110, totaling 272 studies for SI analysis. SI was reported in 89% of studies, but often lacked depth and strategic planning. Stakeholders were mainly engaged during the preparatory phase. Most studies involved micro- and meso-level stakeholders, rarely including macro-level stakeholders. Few described stakeholder selection or preparation. SI was mostly consultative, via interviews, surveys, and focus groups, with limited active collaboration. SI processes and costs were rarely evaluated. Our findings underscore the need for structured, comprehensive SI planning and offer practical recommendations to strengthen SI efforts in implementation research.}, } @article {pmid40571723, year = {2025}, author = {Li, TY and Gao, AW and Yang, R and Sun, Y and Lei, Y and Li, X and Chen, L and Liu, YJ and Arey, RN and Morales, K and Liu, RB and Wang, W and Zhou, A and Zhao, TJ and Li, W and Lalou, A and Wang, Q and Lima, T and Houtkooper, RH and Auwerx, J}, title = {A lysosomal surveillance response to stress extends healthspan.}, journal = {Nature cell biology}, volume = {27}, number = {7}, pages = {1083-1097}, pmid = {40571723}, issn = {1476-4679}, support = {ERC-AdG-787702//EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council)/ ; SNSF 31003A_179435; Sinergia CRSII5_202302//Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (Swiss National Science Foundation)/ ; NRF 2017K1A1A2013124//National Research Foundation of Korea (NRF)/ ; LT000731/2018-L//Human Frontier Science Program (HFSP)/ ; PF-19-0232//United Mitochondrial Disease Foundation (UMDF)/ ; 82300708//National Natural Science Foundation of China (National Science Foundation of China)/ ; }, mesh = {*Lysosomes/metabolism/genetics ; *Caenorhabditis elegans/genetics/metabolism ; Animals ; *Caenorhabditis elegans Proteins/metabolism/genetics ; *Longevity/genetics ; *Stress, Physiological ; Vacuolar Proton-Translocating ATPases/genetics/metabolism ; Humans ; Proteolysis ; Disease Models, Animal ; }, abstract = {Lysosomes are cytoplasmic organelles central for the degradation of macromolecules to maintain cellular homoeostasis and health. However, how lysosomal activity can be boosted to counteract ageing and ageing-related diseases remains elusive. Here we reveal that silencing specific vacuolar H[+]-ATPase subunits (for example, vha-6), which are essential for intestinal lumen acidification in Caenorhabditis elegans, extends lifespan by ~60%. This longevity phenotype can be explained by an adaptive transcriptional response typified by induction of a set of transcripts involved in lysosomal function and proteolysis, which we termed the lysosomal surveillance response (LySR). LySR activation is characterized by boosted lysosomal activity and enhanced clearance of protein aggregates in worm models of Alzheimer's disease, Huntington's disease and amyotrophic lateral sclerosis, thereby improving fitness. The GATA transcription factor ELT-2 governs the LySR programme and its associated beneficial effects. Activating the LySR pathway may therefore represent an attractive mechanism to reduce proteotoxicity and, as such, potentially extend healthspan.}, } @article {pmid40569742, year = {2025}, author = {Kimonis, ER and Gooi, CH}, title = {Treating populations with antagonistic traits-Reflections on Hyatt, Phillips, et al. (2025) and considerations for clinical psychology training programs.}, journal = {Personality disorders}, volume = {16}, number = {4}, pages = {310-314}, doi = {10.1037/per0000719}, pmid = {40569742}, issn = {1949-2723}, support = {//The University of New South Wales/ ; }, mesh = {Humans ; *Psychology, Clinical/education ; *Antisocial Personality Disorder/therapy ; *Clinical Competence ; *Conduct Disorder/therapy ; }, abstract = {The treatment of populations with antagonistic traits and disorders, particularly psychopathic personalities, poses a significant challenge for mental health practitioners and trainees. This commentary reviews Hyatt, Phillips, et al. (2025), highlighting the critical clinical training gaps related to working with individuals exhibiting externalizing and antagonistic behaviors. Hyatt, Phillips, et al.'s (2025) findings reveal that graduate students receive less training and experience working with these populations compared to clients with internalizing disorders, contributing to lower self-efficacy and greater emotional strain in therapeutic encounters. This commentary discusses the urgent need for enhanced training, including exposure to structured evidence-based interventions for child conduct disorders, such as Parent-Child Interaction Therapy and its adaptation for children with callous-unemotional traits. It also discusses possible reasons for Hyatt, Phillips, et al.'s (2025) findings, including the pervasive underfunding of research on conduct disorders and psychopathy, which contributes to the scarcity of effective treatments. Finally, future training initiatives are considered, including the potential of novel training techniques such as deliberate practice and simulation-based education to improve psychology trainee's clinical competence in working with clients with antagonism. This commentary emphasizes the importance of equipping future clinicians with the skills needed to address the complex needs of these challenging populations to help reduce their societal burden. (PsycInfo Database Record (c) 2025 APA, all rights reserved).}, } @article {pmid40564630, year = {2025}, author = {Papastefanou, T and Binos, P and Minaidou, D and Petinou, K and Christophi, CA and Theodorou, E}, title = {Delivery of Pediatric Student-Led Speech and Language Therapy Services at a University Rehabilitation Clinic in Cyprus: Children Accessing Services.}, journal = {Children (Basel, Switzerland)}, volume = {12}, number = {6}, pages = {}, pmid = {40564630}, issn = {2227-9067}, abstract = {Background/Objectives: Early identification and intervention in speech and language therapy (SLT) are essential for children's academic, social, and emotional development. In Cyprus, barriers such as long waiting lists, financial constraints, and limited public awareness restrict access to SLT services. University-led clinics offer a promising alternative by providing affordable, accessible care while training future clinicians. This study aimed to examine the demographic profiles, referral pathways, and diagnostic patterns of children accessing services at a university-led SLT clinic. By documenting referral trends and diagnostic outcomes, this study offers preliminary insights into patterns of service use and potential access disparities in the Cypriot context. Methods: A retrospective analysis was conducted using records from 235 children, aged 0;7 to 15 years, assessed at the University Rehabilitation Clinic between 2015 and 2024. Data included age, gender, socioeconomic status (SES), bilingualism, referral source, and diagnostic outcomes. Diagnoses were classified using Bishop et al.'s (2016) framework. Results: Significant associations were identified between age, parental education, referral source, and diagnostic category. Older children (9;1-12 years) demonstrated a markedly increased likelihood of receiving a developmental language disorder (DLD) diagnosis. Higher parental education levels and referrals from teachers or parents were also predictive of DLD and other communication impairments. Bilingualism was not a significant predictor of diagnostic category. Conclusions: The findings suggest that university-led clinics may serve as an important access point for underserved populations in Cyprus. This study provides preliminary evidence concerning demographic and referral factors that can inform outreach strategies and future service planning.}, } @article {pmid40562989, year = {2025}, author = {Burgoyne, AP and Frank, DJ and Macnamara, BN}, title = {Complex span and the n-back lack convergent validity as measures of working memory: Reply to Wilhelm et al. (2025).}, journal = {Psychonomic bulletin & review}, volume = {}, number = {}, pages = {}, pmid = {40562989}, issn = {1531-5320}, support = {W911NF-22-1-0226//Army Research Institute for the Behavioral and Social Sciences/ ; }, abstract = {In our target article, "Which Working Memory Are We Talking About? N-Back vs. Complex Span Tests," we analyzed data from 1,272 participants and demonstrated that complex span and n-back tasks lack convergent validity as measures of working memory. Evidence for their dissociation included 1) exploratory factor analyses revealing two distinct factors with near-zero cross-loadings, 2) confirmatory factor analyses showing these factors share one-fifth of their reliable variance, and 3) both factors correlating more strongly with fluid intelligence than with each other. Structural equation modeling demonstrated that n-back and complex span factors each explained significant unique variance in fluid intelligence (24% and 14% respectively), beyond their jointly explained variance (30%). These findings align with previous meta-analytic results and support a theoretical framework where complex span tasks emphasize information maintenance while n-back tasks require rapid disengagement from outdated information. Our analyses extended beyond method-specific effects by replicating these results at the broader construct level with additional measures of updating and working memory capacity. In their commentary, Wilhelm et al.'s alternative single-factor model suggests a near-perfect association between working memory and fluid intelligence (β = .97). Their model relies on inconsistently applied correlated error terms selected through a data-driven approach. Notably, modification indices suggest improvements to their model that would bring it closer to our two-factor structure, consisting of clusters of measures representing working memory capacity on one hand and updating on the other. Recognizing these distinctions advances our understanding of cognitive abilities and helps avoid the jingle fallacy.}, } @article {pmid40557867, year = {2025}, author = {Merrill, KG and Dougherty, A and Battalio, SL and Hartstein, ML and Silva, A and Moskowitz, DA and De Pablo, MG and Margellos-Anast, H and Baumann, AA and Navalpakkam, P and Sandoval, A and Bailey, L and Chapman, M and DiCesare, J and Ortiz, E and Habibi, B and Bautista, BA and Martinez, I and Wilson, N and Martin, MA}, title = {Implementing capacity-building initiatives addressing health equity through community-academic partnerships: A qualitative study.}, journal = {Translational behavioral medicine}, volume = {15}, number = {1}, pages = {}, pmid = {40557867}, issn = {1613-9860}, support = {OT2HL161610/NH/NIH HHS/United States ; }, mesh = {Humans ; *Capacity Building ; *Health Equity ; Qualitative Research ; *Community-Institutional Relations ; Focus Groups ; Implementation Science ; Universities ; }, abstract = {BACKGROUND: Capacity-building is a common goal of community-academic partnerships, but there are literature gaps in the components of capacity-building efforts that support success and how implementation science can contribute to these efforts. We studied the core components and implementation determinants of capacity-building initiatives carried out through Chicagoland CEAL community-academic partnerships.

METHODS: We conducted seven focus group discussions with 26 community organization representatives and researchers exploring six capacity-building initiatives. We used Juckett et al.'s typology to summarize the initiatives' core components and grouped emerging themes on implementation determinants according to the domains and constructs of the Exploration, Preparation, Implementation, Sustainment (EPIS) implementation science framework.

RESULTS: The core components of the capacity-building initiatives varied widely in their use of didactic, practical application, knowledge-sharing, and technical assistance activities, but the implementation barriers and facilitators showed greater consistency. Bridging factors: Findings demonstrated the importance of developing mutually beneficial, trusting relationships among community-academic partners with clear goals. Innovation factors: Tailoring capacity-building activities to populations' needs and adapting over time were notable facilitators. Outer context: Flexible funding supported implementation, while social climate and local infrastructure limitations were barriers. Inner context: Barriers included competing priorities, space limitations, and staff availability.

CONCLUSIONS: Our findings on core components, barriers, and facilitators can promote the equitable implementation of capacity-building initiatives carried out by community-academic partnerships. Our study addresses calls to place greater emphasis on health equity and attention to context in the field of implementation science. Our findings further strengthen the literature on the EPIS framework through practical application.}, } @article {pmid40551453, year = {2025}, author = {Ahmad, AAK and Tehan, PE and Hopson, AM and Roberts, EG and Rose, AJ}, title = {Evaluation of eHealth Interventions to Prevent Pressure Injuries: A Scoping Review.}, journal = {International wound journal}, volume = {22}, number = {7}, pages = {e70680}, pmid = {40551453}, issn = {1742-481X}, support = {G2300448//University of Newcastle, College of Health, Medicine and Well-being: CWMWB Industry Pilot/ ; }, mesh = {Humans ; *Pressure Ulcer/prevention & control ; *Telemedicine ; Male ; Female ; }, abstract = {The aim of this scoping review was to map the literature pertaining to the use of eHealth interventions to prevent pressure injuries in populations at risk of the complication, and describe the interventions encountered with the help of Greenhalgh et al.'s Nonadoption, Abandonment, Scale-up, Spread and Sustainability framework. Articles were retrieved using database queries to CINAHL, Medline, ScienceDirect and the Cochrane library with a search string strategy that considered articles from the inception of each database until the 29th of January 2024. The interventions from the 27 included studies were then evaluated using the Nonadoption, Abandonment, Scale-up, Spread and Sustainability framework. The included studies had a publication date range from 1997 to 2023 and included diverse study designs encompassing experimental trials, qualitative designs, mixed-methods, cohort studies and randomised control trials (including secondary analyses). There was a preference for app-based interventions (15/27) that are installed on smartphones, while other interventions encompassed a bed with sensors that automatically adjusted air cell pressure, clinical support algorithms and continuous sensing devices. In conclusion, this scoping review provides an overview of the various technological solutions currently available for pressure injury prevention as well as recommendations for improving the long-term adoption of future eHealth interventions.}, } @article {pmid40544661, year = {2025}, author = {Zelek, WM and Tenner, AJ}, title = {Complement therapeutics in neurodegenerative diseases.}, journal = {Immunobiology}, volume = {230}, number = {4}, pages = {153089}, doi = {10.1016/j.imbio.2025.153089}, pmid = {40544661}, issn = {1878-3279}, mesh = {Humans ; *Neurodegenerative Diseases/immunology/therapy/drug therapy/metabolism/etiology ; *Complement System Proteins/metabolism/immunology ; Animals ; Brain/immunology ; Complement Activation/drug effects ; }, abstract = {Neurodegenerative diseases (NDDs) such as Alzheimer's, Parkinson's, and amyotrophic lateral sclerosis pose considerable therapeutic challenges, not only due to their complex pathophysiology, but also because any effective drug must be capable of penetrating the brain. Inflammation is a key feature of NDDs. Increasingly, the complement system, long studied in the context of host defence, has emerged as a central player in the brain, with roles extending far beyond its classical immune functions. Complement contributes to synaptic pruning and immune surveillance, but when dysregulated, it can drive chronic inflammation, synapse loss, and neurodegeneration. Complement is also implicated in neurodevelopmental and neuropsychiatric diseases, including schizophrenia and mood disorders, where overactivation of the cascade impacts brain maturation and circuit stability. In this review, we take a broad view of roles of the complement system in both health and disease in the central nervous system (CNS). We summarise key mechanisms through which complement contributes to pathology, discuss emerging therapeutic strategies, and consider major hurdles in CNS drug development, including brain delivery and the need for patient stratification. As our understanding of the pathological roles of the complement system in the brain advances, it is becoming clear that complement therapeutics may offer a novel approach in slowing neurodegeneration, and in addressing a broader spectrum of disorders affecting the brain.}, } @article {pmid40543562, year = {2025}, author = {Pope, E and Ameral, V and Falcón, A and Smith, J and Shoemaker-Hunt, SJ and Bounthavong, M and McCullough, M and Kim, B}, title = {Knowledge and attitudes regarding substance use disorder treatment and harm reduction practices among US pharmacists: a scoping review.}, journal = {Journal of the American Pharmacists Association : JAPhA}, volume = {}, number = {}, pages = {102462}, doi = {10.1016/j.japh.2025.102462}, pmid = {40543562}, issn = {1544-3450}, abstract = {BACKGROUND: Pharmacists are uniquely positioned to address substance use disorders (SUDs) and expand harm reduction services due to their accessibility and expertise in medication management. However, attitudinal and structural barriers may limit their full potential in this role.

OBJECTIVE: This scoping review examines pharmacists' knowledge, attitudes, and engagement in SUD treatment and harm reduction.

METHODS: A scoping review was conducted using Levac et al.'s enhancement of Arksey and O'Malley's framework. A systematic search of MEDLINE (PubMed), PsycInfo, Embase, ProQuest Health & Medical, and ProQuest Psychology was performed on August 3, 2024, yielding 87 articles addressing pharmacists' knowledge, attitudes, and practices related to SUD and harm reduction.

RESULTS: Pharmacists generally acknowledge the efficacy of medications for opioid use disorder (MOUDs) in reducing opioid-related mortality but often hold stigmatizing beliefs about individuals with SUDs. While supportive of harm reduction strategies, such as naloxone distribution and needle and syringe programs, engagement varies widely. Significant gaps in education and training persist, leaving pharmacists with limited confidence and practical experience in SUD care, despite their reported familiarity with MOUDs and naloxone pharmacology.

CONCLUSION: This review highlights a complex interplay of support, barriers, and knowledge gaps shaping pharmacists' roles in SUD treatment and harm reduction. Targeted education, supportive policies, and interprofessional collaboration are crucial to enabling pharmacists to provide stigma-free, comprehensive care for individuals with SUDs.}, } @article {pmid40540117, year = {2025}, author = {Blanchet Garneau, A and Lavoie, P and Bélisle, M and Cassivi, C and Chamoun, L and Bytyqi, T}, title = {Outcomes of antiracist pedagogy in health professions education: a scoping review.}, journal = {Advances in health sciences education : theory and practice}, volume = {}, number = {}, pages = {}, pmid = {40540117}, issn = {1573-1677}, abstract = {In health professions education, there is a call to rethink pedagogical practices and institutions that often perpetuate racism, colonialism, and other systems of oppression. Researchers have stressed the importance of integrating critical pedagogies, such as antiracist pedagogy, to help learners understand societal and structural factors behind health inequities and recognize power dynamics in health science and healthcare. Various antiracist pedagogical interventions have been designed, but their outcomes remain unclear. Based on Levac et al.'s framework, a scoping review was conducted to map the literature evaluating the outcomes of antiracist pedagogy in health professions education. A systematic database search was conducted between April and June 2022 for articles describing evaluation methods and outcomes of antiracist pedagogical interventions in health professions education. We included 41 articles in the final selection. The data was organized within the following themes: aim of intervention, type of intervention, evaluation tools, outcomes and indicators for each of Kirkpatrick's levels of training evaluation, theoretical frameworks, and authors' positionalities. The thematic analysis revealed that, in most cases, evaluations targeted participants' attitudes on systemic racism, their racial identity and critical awareness, as well as their satisfaction with the activities. The antiracist pedagogical interventions were rarely evaluated beyond learners' perceptions. Discrepancies were also raised between the principles of antiracist education and the use of antiracist pedagogy to design, implement and evaluate the outcomes of antiracist pedagogical interventions in health professions education. Although only a few interventions had transformative outcomes beyond individuals, we identified promising pedagogical strategies to foster engagement and motivation to transform professional practices.}, } @article {pmid40534156, year = {2025}, author = {Persson, S and Liljegren, AE and Olsson, C and Rydén, P}, title = {Use and Perception of Video Consultations Among Swedish Dietitians Before and After COVID-19 Onset.}, journal = {Journal of human nutrition and dietetics : the official journal of the British Dietetic Association}, volume = {38}, number = {3}, pages = {e70080}, pmid = {40534156}, issn = {1365-277X}, support = {//This study was supported by Företagsforskarskolan för Samverkan och Innovation, Umeå Universitet and The Swedish Centre for Rural Health, Region Västerbotten./ ; }, mesh = {Humans ; *COVID-19/epidemiology ; Sweden/epidemiology ; *Nutritionists/psychology/statistics & numerical data ; Male ; Female ; *Telemedicine/statistics & numerical data ; Adult ; Middle Aged ; Surveys and Questionnaires ; SARS-CoV-2 ; *Remote Consultation/statistics & numerical data ; *Dietetics ; Pandemics ; Health Services Accessibility ; *Videoconferencing ; Perception ; }, abstract = {INTRODUCTION: The implementation of telehealth began globally before the onset of COVID-19 but the use of telehealth, particularly video consultations (VCs), is expected to have increased with pandemic restrictions on face-to-face consultations (FTFCs). However, little is known about its actual usage. In Sweden, VCs have the potential to bridge long distances between Registered Dietitians (RDs) and their patients. This study investigates the use and perceptions of VCs among Swedish RDs before and after the onset of COVID-19.

METHODS: Swedish RDs were invited to participate in web-based surveys in 2016 (n = 61) and 2021 (n = 112). Data are analysed and later discussed through the lens of Levesque et al.'s framework for patient-centred access to healthcare.

RESULTS: More RDs reported having VC-experience in 2021 compared to the 2016 survey, 67% and 16% respectively. A majority of the RDs (85%-88%) believed that access to dietetic care would increase with the use of VCs compared to FTFCs. In 2021, about half of RDs (55% and 46%) perceived treatment quality and relational quality to be unaffected by VCs, while approximately one-third (31% and 43%) saw it as being reduced. With their additional experience, there was the caution by 69% of RDs in 2021 that consultations requiring language interpretation services were less suitable for VCs.

CONCLUSIONS: The findings suggest broader VC usage among Swedish RDs participating in the study. Implications for clinical practice include maintained access to healthcare and further practice development to meet quality needs and increased equity.}, } @article {pmid40529804, year = {2025}, author = {Yolay, O and Kasapbasi, EE and Tezcan, E and Kucuk, C and Karaoglu, H and Canturk, E and Inan, B and Oksen, D and Cetinarslan, O and Umihanić, F and Albayrak, SB and Olcay, A}, title = {Postmortem Inductively Coupled Plasma Mass Spectrometry Analysis Reveals Elevated Heavy Metal Concentrations in Coronary Arteries: A Comparative Autopsy Study Supporting a Toxic Inflammatory Hypothesis for Atherosclerosis.}, journal = {Biomedicine hub}, volume = {10}, number = {1}, pages = {124-133}, pmid = {40529804}, issn = {2296-6870}, abstract = {INTRODUCTION: A large number of studies have been carried out for the etiology of atherosclerosis and many risk factors have been identified, including environmental factors and heavy metals, which are related to the pathogenesis. This study aimed to determine the effects of heavy metals, which have activation and inhibition effects on various metabolic pathways, on atherosclerosis by examining coronary arteries obtained from autopsy series.

METHODS: Coronary arteries of 28 autopsy cases were analyzed by inductively coupled plasma mass spectrometry method. Sixteen of the cases had coronary atherosclerotic plaques and 12 of the coronaries were normal. Twenty trace metal concentrations were examined from the samples obtained.

RESULTS: Twenty-eight coronary artery samples (16 with atherosclerosis, 12 normal) were analyzed using ICP-MS. Levels of Mg, K, Ca, P, Fe, Zn, Al, S, As, Pt, Sb, Hg were significantly higher in atherosclerotic arteries (e.g., Ca: 51,384 vs. 1,723 ppm, p = 0.005; P: 30,791 vs. 3,443 ppm, p = 0.003; Hg: 3.2 vs. 0 ppm, p < 0.001). Elements such as lead, cobalt, and cadmium remained below detection limits in both groups.

CONCLUSION: Heavy metals through inflammation, oxidative stress, and disrupted antioxidant pathways are independent risk factors that increase the risk of atherosclerosis. These findings provide tissue-level evidence that heavy metal accumulation may contribute to atherosclerosis through oxidative stress, inflammation, and disruption of antioxidant defenses.}, } @article {pmid40529731, year = {2025}, author = {Liu, F and Huang, Y and Chen, C and Chen, L and Huang, X and Dong, Z and Jiang, H and He, Y and Xue, W}, title = {Application and validation of a newly developed lung donor (LUNDON) acceptability score for lung transplantation: a retrospective cohort study.}, journal = {Journal of thoracic disease}, volume = {17}, number = {5}, pages = {3297-3306}, pmid = {40529731}, issn = {2072-1439}, abstract = {BACKGROUND: Organ shortage remains a considerable challenge in the field of lung transplantation. There is an urgent need now for a new standard that can include more donor lungs and expand the donor pool to benefit more patients. To increase lung utilization rates and facilitate the standardization of the lung donor evaluation process, Heiden et al. formulated a novel lung donor (LUNDON) acceptability score. Our study applied data from a Chinese hospital to this model to demonstrate the practicability of the new model and reveal its potential to expand the donor lung pool and improve the efficiency and success rate of lung transplantation.

METHODS: This study was conducted in one of the largest lung transplant centers in China. Our study retrospectively analyzed a cohort of patients who underwent lung transplantation in Wuxi People's Hospital, Jiangsu Province, China, between January 1, 2018 and December 31, 2022, and applied the same exclusion criteria as those described in Heiden et al.'s study. The LUNDON score is an integer score established based on the model. Higher scores correspond to an increased likelihood of lung acceptance.

RESULTS: A total of 553 donor lungs were used for transplantation. According to the LUNDON score, the donors' integer-based score ranged from 9 to 30 points, and the predicted probability of donor lung acceptance was about 6.0% to 95.3%. Utilization of low-LUNDON-score donors increased progressively over the study period. The LUNDON score demonstrated concordance with the lung acceptance rate as designated by the International Society for Heart and Lung Transplantation (ISHLT) standard score. There was a statistically significant difference in the survival rate between donors and recipients with high or low LUNDON scores (P=0.03). The survival rate at 1 year after transplantation was 66.1% for the high-score group and 55.7% for the low-score group. The LUNDON score, as a newly developed practical model, can promote a further understanding of donor lung assessment and has the potential to effectively expand the donor pool.

CONCLUSIONS: This study confirmed the practicability of the newly developed lung donor (LUNDON) scoring model. The LUNDON score was found to be a valuable tool and may revolutionize and optimize the allocation of scarce organ resources. It is possible that the novel model can be applied to various populations, expand the pool of potential available lungs, and enhance the efficiency and success of lung transplantation.}, } @article {pmid40529608, year = {2025}, author = {Hailu, DT and Melaku, MS and Abebe, SA and Walle, AD and Tilahun, KN and Gashu, KD}, title = {A modified UTAUT model for acceptance to use telemedicine services and its predictors among healthcare professionals at public hospitals in North Shewa Zone of Oromia Regional State, Ethiopia.}, journal = {Frontiers in digital health}, volume = {7}, number = {}, pages = {1469365}, pmid = {40529608}, issn = {2673-253X}, abstract = {INTRODUCTION: The shortage of healthcare professionals, long waiting time for treatment, inadequate transportation, and hard-to-reach geographical locations remained challenging in the healthcare service delivery in resource-limited settings. To overcome these challenges, healthcare providers are looking to use telemedicine technologies as an alternative solution. However, user resistance has consistently been identified as a major obstacle to the successful implementation of telemedicine. Thus, this study aimed to assess acceptance to use telemedicine services and its predictors among healthcare professionals at public hospitals in the North Shewa Zone of Oromia Regional State, Ethiopia.

METHOD: A cross-sectional study design was employed among a total of 627 healthcare professionals working at public hospitals in the North Shewa Zone from 3 April to 1 May 2023. The study participants were selected using simple random sampling techniques. A questionnaire, which is adapted from the original instrument developed by Venkatesh et al.'s study and several studies regarding the UTAUT model was used. Data were collected using a self-administered structured questionnaire in English version. The descriptive statistics were estimated using the SPSS version 25, and structural equation modeling analysis was employed using AMOS V.21 software.

RESULTS: In this study, 601 (95.85% response rate) study subjects participated. The study has shown that 315 (52.4%) (95% CI: 48.3-56.5) of the participants accepted to use telemedicine in their routine healthcare services. Performance expectancy (β = 0.184, p = 0.001), effort expectancy (β = 0.183, p < 0.001), facilitating conditions (β = 0.249, p < 0.001), and digital literacy (β = 0.403, p < 0.001) had a significant positive effect on the acceptance to use telemedicine services. Age was used to moderate facilitating conditions (β = 0.400, p < 0.001) and digital literacy (β = 0.598, p < 0.001) in relation to acceptance to use telemedicine services.

CONCLUSION: The healthcare professionals' acceptance to use the offered telemedicine services was promising for the future. Additionally, our research found significant effects between healthcare professionals' acceptance to use telemedicine services with the predictors except social influence. Facilitating conditions and digital literacy with acceptance to use were moderated by age. Thus, the health facility should strengthen its telemedicine technology by raising awareness of its usefulness and ease of use.}, } @article {pmid40525994, year = {2025}, author = {Feldman, LM and Lian, L and Ahmed, N and Chen, BY}, title = {Using the Six-Step Approach for Curriculum Development in a Blended Learning Dentistry Curriculum.}, journal = {JDR clinical and translational research}, volume = {10}, number = {1_suppl}, pages = {76S-83S}, doi = {10.1177/23800844251328668}, pmid = {40525994}, issn = {2380-0852}, mesh = {*Curriculum/standards ; Humans ; *Education, Dental/methods/standards ; Students, Dental/psychology ; *Pediatric Dentistry/education ; Faculty, Dental ; }, abstract = {PURPOSE/OBJECTIVES: This study documents lessons learned from the revision of the predoctoral advanced pediatric dentistry course administered during the academic year 2019-2020. Insight on the use of and recommendations for adopting the Six-Step Approach for dental curriculum revision are provided.

METHODS: Thomas et al.'s Curriculum Development for Medical Education: A Six-Step Approach was adapted and applied by dental faculty after the predoctoral director completed a Medical Education Principles and Practice course. Literature review, anonymous student and faculty surveys administered via Qualtrics, individual faculty feedback sessions, and aggregate course data were assessed.

RESULTS: The identification of the specific health care problem to be solved and the assessment of targeted learners and learning environment helped clarify course goals and specific measurable objectives. With a shared understanding of learners' needs, faculty united in adopting new educational strategies to promote the achievement of revised objectives. This facilitated rapid course implementation. Evaluation results demonstrated increased student engagement and faculty satisfaction.

CONCLUSIONS: The framework provided by the Six-Step Approach aided the revision of the pediatric dental curriculum, clarified goals of promoting learner engagement, and increased faculty enjoyment of teaching. Dental educators may find this framework useful when revising their curricula.Knowledge Transfer Statement:This article aims to support dental educators in familiarizing themselves with and using a defined approach to curriculum development.}, } @article {pmid40519824, year = {2025}, author = {Michalec, B and Forbes, CE and Pardon, K and Ayala, B and Beltran, DG and Douille, C and Felix, K and Gnall, S and Hoenack, M and McKeever, B and Nguyen, D and Piemonte, N and Portle, S}, title = {A scoping review of emotional contagion research with human subjects: identifying common trends of previous research and potential areas for future research.}, journal = {Frontiers in psychology}, volume = {16}, number = {}, pages = {1573375}, pmid = {40519824}, issn = {1664-1078}, abstract = {INTRODUCTION: Emotional contagion (EC) involves the automatic mimicry and synchronization of expressions, vocalizations, and movements, resulting in emotional alignment between individuals. Despite consistent scholastic explorations of the various nuances and tenets associated with emotional contagion processes and outcomes, there has yet to be a thorough review of human subjects-based emotional contagion research.

METHODS: This review examines human subjects EC research trends, analyzing 277 articles (published from 1992 to 2022) to identify common conceptualizations, triggers, and measurement methods.

RESULTS: Analyses indicated that Hatfield et al.'s classic conceptualization is the most cited, and common triggers include facial expressions in images and videos, and real-time interactions - though many studies did not stimulate EC. While many studies did utilize validated EC scales, about 28% of the studies reviewed used non-validated questions to measure EC. Moreover, the EC research reviewed heavily relies on college-aged, predominantly white participants, indicating a need for more diverse samples.

DISCUSSION: Future EC research should explore processes and nuances associated with EC among older adults, minoritized groups, and diverse contexts (e.g., healthcare, schools), using novel triggers and multiple measurement methods.}, } @article {pmid40517843, year = {2025}, author = {Guberina, M and Rating, P and Sokolenko, E and Jabbarli, L and Kiefer, T and Biewald, E and Guberina, N and Fiorentzis, M and Bechrakis, N and Flühs, D and Stuschke, M}, title = {Response to: Commentary on Maja Guberina et al.'s study of dose response relation for optic nerve atrophy at low-dose rate brachytherapy of uveal melanoma.}, journal = {Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology}, volume = {209}, number = {}, pages = {110989}, doi = {10.1016/j.radonc.2025.110989}, pmid = {40517843}, issn = {1879-0887}, } @article {pmid40517842, year = {2025}, author = {Wang, Z and Guan, W and Bu, M and Lu, S and Zhao, H}, title = {Commentary on Maja Guberina et al.'s study of dose response relation for optic nerve atrophy at low-dose rate brachytherapy of uveal melanoma.}, journal = {Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology}, volume = {209}, number = {}, pages = {110986}, doi = {10.1016/j.radonc.2025.110986}, pmid = {40517842}, issn = {1879-0887}, } @article {pmid40504117, year = {2025}, author = {Morgan, KJ and Carley, E and Coyne, AN and Rothstein, JD and Lusk, CP and King, MC}, title = {Visualizing nuclear pore complex plasticity with pan-expansion microscopy.}, journal = {The Journal of cell biology}, volume = {224}, number = {9}, pages = {}, pmid = {40504117}, issn = {1540-8140}, support = {R01 NS122236/NH/NIH HHS/United States ; F31 HL158119/NH/NIH HHS/United States ; F31 HL158119/HL/NHLBI NIH HHS/United States ; R35 GM15374/NH/NIH HHS/United States ; R01 NS122236/NS/NINDS NIH HHS/United States ; R01 GM129308/GM/NIGMS NIH HHS/United States ; 2420904//National Science Foundation/ ; R01 GM129308/NH/NIH HHS/United States ; }, mesh = {*Nuclear Pore/metabolism/ultrastructure ; Humans ; Induced Pluripotent Stem Cells/metabolism ; Neurons/metabolism ; Amyotrophic Lateral Sclerosis/pathology/genetics/metabolism ; C9orf72 Protein/genetics/metabolism ; Nuclear Envelope/metabolism ; *Microscopy/methods ; Membrane Glycoproteins ; }, abstract = {The exploration of cell-type and environmentally responsive nuclear pore complex (NPC) plasticity requires new, accessible tools. Using pan-expansion microscopy (pan-ExM), NPCs were identified by machine learning-facilitated segmentation. They exhibited a large range of diameters with a bias for dilated NPCs at the basal nuclear surface in clusters suggestive of local islands of nuclear envelope tension. Whereas hyperosmotic shock constricted NPCs analogously to those found in annulate lamellae, depletion of LINC complexes specifically eliminated the modest nuclear surface diameter biases. Therefore, LINC complexes may contribute locally to nuclear envelope tension to toggle NPC diameter between dilated, but not constricted, states. Lastly, POM121 shifts from the nuclear ring to the inner ring of the NPC specifically in induced pluripotent stem cell-derived neurons from a patient with C9orf72 amyotrophic lateral sclerosis. Thus, pan-ExM is a powerful tool to visualize NPC plasticity in physiological and pathological contexts at single NPC resolution.}, } @article {pmid40502754, year = {2025}, author = {Lorincz-Comi, N and Song, W and Chen, X and Paz, IR and Hou, Y and Zhou, Y and Xu, J and Martin, W and Barnard, J and Pieper, AA and Haines, JL and Chung, M and Cheng, F}, title = {Combining xQTL and genome-wide association studies from ethnically diverse populations improves druggable gene discovery.}, journal = {Research square}, volume = {}, number = {}, pages = {}, pmid = {40502754}, issn = {2693-5015}, support = {R21 AG083003/AG/NIA NIH HHS/United States ; R01 AG082118/AG/NIA NIH HHS/United States ; R56 AG074001/AG/NIA NIH HHS/United States ; RF1 AG082211/AG/NIA NIH HHS/United States ; R01 AG084250/AG/NIA NIH HHS/United States ; RF1 NS133812/NS/NINDS NIH HHS/United States ; U01 AG073323/AG/NIA NIH HHS/United States ; R01 AG066707/AG/NIA NIH HHS/United States ; R01 AG076448/AG/NIA NIH HHS/United States ; }, abstract = {Repurposing existing medicines to target disease-associated genes represents a promising strategy for developing new treatments for complex diseases. However, progress has been hindered by a lack of viable candidate drug targets identified through genome-wide association studies (GWAS). Gene-based association tests provide a more powerful alternative to traditional single nucleotide polymorphism (SNP)-based methods, yet current approaches often fail to leverage shared heritability across populations and to effectively integrate functional genomic data. To address these challenges, we developed GenT and its various extensions, comprising a framework of gene-based tests utilizing summary-level GWAS data. Using GenT, we identified 16, 15, 35, and 83 druggable genes linked to Alzheimer's disease (AD), amyotrophic lateral sclerosis, major depression, and schizophrenia, respectively. Additionally, our multi-ancestry gene-based test (MuGenT) uncovered 28 druggable genes associated with type 2 diabetes that previous trans-ancestry or ancestry-specific GWAS had missed. By integrating brain expression and protein quantitative trait loci (e/pQTLs) into our analysis, we identified 43 druggable genes (e.g., RIPK2, NTRK1, RIOK1) associated with AD that had supporting xQTL evidence. Notably, experimental assays demonstrated that the NTRK1 protein inhibitor GW441756 significantly reduced tau hyper-phosphorylation (including p-tau181 and p-tau217) in AD patient-derived iPSC neurons, thus providing mechanistic support for our predictions. Overall, our findings underscore the power of gene-based association testing as a strategic tool for informed drug target discovery and validation based on human genetic and genomic data for complex diseases.}, } @article {pmid40498248, year = {2025}, author = {Pahwa, R and Molho, E and Lew, M and Dashtipour, K and Gil, RA and Revilla, FJ and Clinch, T and Qin, P and Isaacson, SH and , }, title = {Long-Term Safety and Efficacy of Repeated Cycles of RimabotulinumtoxinB in the Treatment of Chronic Sialorrhea: Results of the OPTIMYST Trial.}, journal = {Neurology and therapy}, volume = {14}, number = {4}, pages = {1553-1567}, pmid = {40498248}, issn = {2193-8253}, abstract = {INTRODUCTION: Botulinum toxin injections into the salivary glands inhibit saliva production by reducing the release of acetylcholine at the parasympathetic nerve terminals within the salivary gland. The phase 3 study reported here assessed the safety, tolerability, and effectiveness of repeated cycles of rimabotulinumtoxinB (RIMA) injections in adults with troublesome sialorrhea.

METHODS: In this phase 3, open-label multicenter study, 187 adult participants with troublesome sialorrhea due to Parkinson disease (65.8%), amyotrophic lateral sclerosis (13.9%), and other etiologies (20.3%) received up to 4 cycles of RIMA treatment (3500 U every 11-15 weeks).

RESULTS: Participants (69% male, 31% female; mean age 64.1 years) had sialorrhea for a mean of 3.2 years at baseline with a mean Unstimulated Salivary Flow Rate (USFR) of 0.63 ± 0.49 g/min. During the first treatment cycle, RIMA significantly reduced the mean±standard deviation (SD) USFR from baseline to week 4 by - 0.34 ± 0.37 g/min (p < 0.0001), and efficacy was maintained through week 13 (- 0.14 ± 0.29 g/min; p < 0.0001). Reductions were maintained at subsequent injection cycles 2-4, with mean absolute USFRs at weeks 4 and 13 of each cycle similar to those of cycle 1. Most adverse events (AEs) were mild, and the most commonly reported AEs in each cycle that were considered to be treatment-related were dry mouth (≤ 15.5% participants/cycle) and dental caries (≤ 6.0% participants/cycle).

CONCLUSION: This study demonstrates that RIMA 3500 U safely reduces saliva production over repeated treatment cycles through 1 year, thereby supporting its utility in the management of troublesome sialorrhea in adults.

GOV IDENTIFIER: NCT02610868.}, } @article {pmid40497325, year = {2025}, author = {Shahid, I and Ahmad, I and Ali, A and Raza, A and Zhang, X and Tang, D and Kallel, M and Abdelmohsen, SAM}, title = {Square octagon haeckelites as efficient photocatalysts with enhanced solar-to-hydrogen conversion and high carrier mobilities.}, journal = {Physical chemistry chemical physics : PCCP}, volume = {27}, number = {25}, pages = {13415-13423}, doi = {10.1039/d5cp01522g}, pmid = {40497325}, issn = {1463-9084}, abstract = {The increasing demand for renewable energy solutions underscores the importance of photocatalytic water splitting as a sustainable technology. In this study, we present a first-principles investigation of synthesized novel square-octagon haeckelite AB compounds (A = Sb, Be, Cd, In, Mg, Zn; B = Al, S, Se, Te, P), revealing their superior photocatalytic properties. These 3D materials exhibit unique square-octagonal geometries, optimized band gaps (1.33-3.83 eV), and favorable band edge alignments for water splitting under both acidic (pH = 0) and neutral (pH = 7) conditions. Notably, AlSb achieves the highest solar-to-hydrogen efficiency of 49.00%, followed by CdTe (38.97%), CdSe (18.35%), and InP (38.21%), outperforming conventional photocatalysts. The study also highlights the exceptional carrier mobilities (μ) of AB haeckelite compounds, with ZnTe achieving an electron mobility of 19.3 × 10[6] cm[2] V[-1] s[-1] and hole mobility of 24.9 × 10[4] cm[2] V[-1] s[-1]. These high mobilities facilitate efficient charge transport and minimize recombination losses, enhancing their photocatalytic performance. Additionally, CdTe and CdSe demonstrate strong visible-light absorption, while MgSe and BeSe excel in ultraviolet absorption, showcasing their versatility for optoelectronic applications. This work establishes AB haeckelite compounds as transformative materials for solar-driven hydrogen production by overcoming conventional photocatalysts' limitations, like poor sunlight utilization and low carrier mobility, paving the way for sustainable energy technologies.}, } @article {pmid40495142, year = {2025}, author = {Matting, L and Pfeifer, K and Sudeck, G and Jung, A and Langhirt, F and Geidl, W}, title = {Physical activity promotion in physical therapy, exercise therapy and other movement-based therapies: a scoping review and content analysis of intervention studies and theoretical works.}, journal = {The international journal of behavioral nutrition and physical activity}, volume = {22}, number = {1}, pages = {72}, pmid = {40495142}, issn = {1479-5868}, mesh = {Humans ; *Exercise ; *Exercise Therapy/methods ; *Health Promotion/methods ; *Physical Therapy Modalities ; Noncommunicable Diseases/therapy ; }, abstract = {BACKGROUND: Movement-based therapists, including physical, exercise, and sport therapists, play a key role in promoting physical activity in individuals with non-communicable diseases. However, no clear consensus exists on effective intervention approaches. This scoping review examines available intervention studies and theoretical works for physical activity promotion in movement-based therapy.

METHODS: In accordance with Colquhoun et al.'s framework and PRISMA-ScR guidelines, we systematically searched PubMed, Scopus, Web of Science, and PsycINFO until March 31, 2024. Eligible records described physical activity-promoting concepts including interventional studies and theoretical works applicable in movement-based therapies for individuals with non-communicable diseases. Data extraction covered assessment, therapeutic content, didactic-methodological principles, and theoretical underpinnings. Interventions were categorized based on behavior change techniques (BCTs), the behavior change wheel, and a clinical reasoning model for clients behavior change. Network analysis explored relationships between therapeutic content and didactic-methodological principles.

RESULTS: Fifty-seven records met inclusion criteria; 77% were intervention studies, and 23% were theoretical works. Most concepts originated from orthopedics/rheumatology (23%), neurology (21%), and oncology (9%), while 12% were generic concepts. Across concepts, 66 biopsychosocial assessment instruments and 60 BCTs were applied (Median BCTs per concept: 11.5, range: 4-37). Key didactic-methodological principles included tailoring/individualization (n = 47), active participation (n = 39), collaborative communication (n = 21), and patient self-responsibility and independence (n = 14). Least mentioned was facilitating positive movement experiences and enjoyment of physical activity (n = 3). Network analysis identified action planning, goal setting, and feedback as central BCTs.

CONCLUSION: This review provides an overview of 57 physical activity promotion concepts used in movement-based therapies for individuals with non-communicable diseases. Findings reveal considerable heterogeneity, highlighting diverse strategies used by movement-based therapists to influence physical activity behavior.

TRIAL REGISTRATION: Open Science Framework (OSF), December 23, 2022 (DOI: https://doi.org/10.17605/OSF.IO/AXZSJ).}, } @article {pmid40493065, year = {2025}, author = {Arredondo Montero, J}, title = {Letter to the Editor: on the use of odds ratios in diagnostic reviews: comment on Shan et al.'s review on biomarkers for pediatric obstructive sleep apnea.}, journal = {European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery}, volume = {}, number = {}, pages = {}, pmid = {40493065}, issn = {1434-4726}, } @article {pmid40491120, year = {2025}, author = {Lin, T and Wu, J}, title = {Comment on Ozgungor et al.'s "Albumin Levels as Prognostic Markers in ICU Mortality".}, journal = {Journal of the College of Physicians and Surgeons--Pakistan : JCPSP}, volume = {35}, number = {6}, pages = {803-804}, doi = {10.29271/jcpsp.2025.06.803}, pmid = {40491120}, issn = {1681-7168}, mesh = {Humans ; Prognosis ; Biomarkers/blood ; *Intensive Care Units ; *Serum Albumin/analysis/metabolism ; *Hospital Mortality ; *Critical Illness/mortality ; }, abstract = {Null.}, } @article {pmid40480480, year = {2025}, author = {Menon, S and Morikawa, L and Tummala, S and Buckner-Petty, S and Chhabra, A}, title = {Response to Douoguih et al.'s Letter to the Editor.}, journal = {Arthroscopy : the journal of arthroscopic & related surgery : official publication of the Arthroscopy Association of North America and the International Arthroscopy Association}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.arthro.2025.05.032}, pmid = {40480480}, issn = {1526-3231}, } @article {pmid40479789, year = {2025}, author = {Hosseini, MM and Masoumian Hosseini, ST and Haghighi, E and Qayumi, K and Ebrahimipour, H and Pourabbasi, A and Koohpaei, A and Alizadeh, M and Shafiei, Z}, title = {The revolutionary impact of 6G technology on empowering health and building a smart society: A scoping review.}, journal = {Computers in biology and medicine}, volume = {194}, number = {}, pages = {110496}, doi = {10.1016/j.compbiomed.2025.110496}, pmid = {40479789}, issn = {1879-0534}, mesh = {Humans ; *Wireless Technology ; Telemedicine ; Delivery of Health Care ; Artificial Intelligence ; Computer Security ; }, abstract = {OBJECTIVE: This scoping review investigates the potential of 6G technology in healthcare, particularly in smart city settings, focusing on its enhanced data capabilities, AI's role in healthcare optimization, infrastructure support, interoperability, quality standards, and privacy and security concerns.

PATIENTS AND METHODS: The scoping review followed the Arksey and O'Malley framework, with Levac et al.'s methodological advancements. The review team searched academic databases like PubMed/Medline, SCOPUS, Embase, Web of Sciences, and IEEE Xplore. They also explored grey literature sources like Google Scholar, OpenGrey, and Web of Science Conference Proceedings. A search strategy was developed, and 145 studies were selected from an initial pool of 9835 records from 2010 to 2025. The review categorized 145 studies into three phases, focusing on deploying 6G technology in healthcare, the infrastructure required, and ethical considerations related to the technology's ethical implications.

RESULT: Phase one focused on advancements like real-time imaging, performing medical procedures remotely, using predictive tools to analyze data, and providing care tailored to individual patients. Phase two examined how the next generation of wireless technology (6G) could interact with communication systems, including techniques to handle large amounts of data (massive MIMO) and using extremely high-frequency signals (terahertz communications) to transfer information faster. Phase three explored ethical concerns about applying 6G technology, such as systems that make decisions based on user intentions (intent-driven management) and organizing information around data-based designs (data-driven architecture). The review highlights how 6G technology could revolutionize patient care and medical services by enabling faster data transfers, reducing delays, increasing system capacity, and incorporating artificial intelligence.

CONCLUSION: The scoping review shows the capability of the transformative potential of 6G technology, particularly in healthcare and urban development, emphasizing its enhanced data transfer speeds, reduced latency, and increased capacity that can significantly improve patient care through better remote monitoring, security, and telemedicine services. It stresses the vital role of policymakers in guiding the development of 6G infrastructure, ensuring effective spectrum allocation, and implementing robust security measures while addressing health and electromagnetic exposure concerns. Policymakers are urged to adopt security-by-design principles, adhere to international standards, and foster collaboration among academia, industry, and government to drive innovation and ensure the responsible deployment of 6G technology. By stimulating research and establishing clear performance metrics, they can facilitate continuous improvement and adaptation, ultimately benefiting society as a whole. The review concludes that strategic policy formulation is essential for maximizing the advantages of 6G technology, leading to more intelligent, productive, and sustainable societal frameworks.}, } @article {pmid40472412, year = {2025}, author = {Sathian, B and Al Hamad, H and Iqbal, J}, title = {Reassessing predictors of non-functioning pituitary macroadenoma growth: Beyond tumor volume.}, journal = {Clinical neurology and neurosurgery}, volume = {256}, number = {}, pages = {108979}, doi = {10.1016/j.clineuro.2025.108979}, pmid = {40472412}, issn = {1872-6968}, mesh = {Humans ; *Pituitary Neoplasms/pathology/diagnosis ; *Adenoma/pathology ; Female ; *Tumor Burden ; Disease Progression ; Male ; Middle Aged ; }, abstract = {Kim et al.'s study (Clinical Neurology and Neurosurgery, 2025;254:108920) investigates the natural history of 232 conservatively managed non-functioning pituitary macroadenomas (NFPMAs), identifying female sex and initial tumor volume (≥2.5 cm[3]) as predictors of growth. While offering valuable insights, the study's reliance on static tumor volume is questioned by recent evidence emphasizing dynamic features (e.g., growth velocity) and molecular markers (e.g., Ki-67, USP8 mutations) as stronger predictors. The reported 47.4 % growth rate may underestimate risks, with other studies noting higher progression (up to 60 %) and visual/hormonal deficits. Furthermore, dismissing age as a predictor contradicts findings linking younger age (<50 years) to increased progression risk. These limitations highlight the need for a more comprehensive approach to NFPMA risk stratification.}, } @article {pmid40471866, year = {2025}, author = {Quaranta, VN and Portacci, A and Lulaj, E and Dragonieri, S and Ferrulli, S and Sana, F and Buonamico, E and Resta, E and Carpagnano, GE}, title = {Real-life preliminary evidence for basophils as predictors of Tezepelumab response in severe asthma.}, journal = {Expert review of clinical immunology}, volume = {21}, number = {7}, pages = {977-989}, doi = {10.1080/1744666X.2025.2517157}, pmid = {40471866}, issn = {1744-8409}, mesh = {Humans ; *Asthma/drug therapy/immunology/diagnosis ; *Basophils/immunology ; Female ; Male ; *Antibodies, Monoclonal, Humanized/therapeutic use ; Adult ; Middle Aged ; Prospective Studies ; *Anti-Asthmatic Agents/therapeutic use ; Biomarkers ; Thymic Stromal Lymphopoietin ; Cytokines ; Treatment Outcome ; Severity of Illness Index ; }, abstract = {BACKGROUND: Severe asthma is a complex disease with persistent symptoms despite high-dose inhaled therapy. Tezepelumab, a monoclonal antibody targeting thymic stromal lymphopoietin (TSLP), has shown efficacy across asthma phenotypes. However, identifying early responders remains a challenge. Basophils, key players in type 2 inflammation, may serve as predictive biomarkers.

OBJECTIVE: We evaluated the presence of super-responder status after six months of Tezepelumab therapy and explored the predictive role of blood basophil levels.

METHODS: A real-life, prospective study was conducted on 16 severe asthma patients. Super-responders were defined per Upham et al.'s criteria, adapted for a six-month assessment. Clinical, functional, and inflammatory parameters, including blood basophil counts, were analyzed.

RESULTS: After six months, 62.5% of patients achieved super-responder status, with complete exacerbation elimination, reduced oral corticosteroid use, and improved asthma control. A significant logarithmic association (p = 0.019) was found between baseline basophil levels and super-responder status, indicating that higher basophil counts were associated with an increased likelihood of super-response. This finding was supported by a trend toward significance in ROC curve analysis (AUC = 0.800, p = 0.050), suggesting potential predictive value.

CONCLUSION: Tezepelumab demonstrates early efficacy in severe asthma, and baseline blood basophil levels may represent a promising biomarker for response prediction.}, } @article {pmid40468792, year = {2025}, author = {Machado, PPP}, title = {EDE and EDE-Q: A Call for Field Wide International Collaboration When Revisiting a Classic, Commentary on Reilly et al. (2025).}, journal = {The International journal of eating disorders}, volume = {}, number = {}, pages = {}, doi = {10.1002/eat.24481}, pmid = {40468792}, issn = {1098-108X}, support = {UID/PSI/01662/2019//Fundação para a Ciência e a Tecnologia/ ; }, abstract = {In their 2025 article in the International Journal of Eating Disorders, Reilly, Gorrell, Chapa, Drury, Stalvey, Goldschmidt, and le Grange examine the widespread use of the Eating Disorder Examination (EDE) and its self-report version, the Eating Disorder Examination-Questionnaire (EDE-Q), in assessing eating disorder symptoms. While acknowledging the popularity of these instruments, the authors highlight important limitations-including restricted scope, psychometric shortcomings, and practical challenges such as inconsistent scoring practices and limited applicability across diverse populations. Rather than advocating for the development of entirely new measures, the authors propose building a field-wide consensus to refine existing tools and promote their broader and more consistent use. Reilly et al.'s paper is a timely and valuable contribution to ongoing conversations about assessment practices in the field. In this commentary, we extend their perspective by drawing on previous experiences in the field that support their call to action and suggest that future consensus efforts should built on international experience and collaboration, and ensure that lived experience voices are integral to the process.}, } @article {pmid40464631, year = {2025}, author = {Jowsey, T and Matthews, R}, title = {Agency: Intention and the eco-systemic dimension. Letter of response to Konopasky et al.'s 2025 conceptualisations of agency (AMEE guide No.177).}, journal = {Medical teacher}, volume = {}, number = {}, pages = {1}, doi = {10.1080/0142159X.2025.2513417}, pmid = {40464631}, issn = {1466-187X}, } @article {pmid40464500, year = {2025}, author = {Dedoni, S and Avdoshina, V and Olianas, MC and Onali, P}, title = {Role of Lysophosphatidic Acid in Neurological Diseases: From Pathophysiology to Therapeutic Implications.}, journal = {Frontiers in bioscience (Landmark edition)}, volume = {30}, number = {5}, pages = {28245}, doi = {10.31083/FBL28245}, pmid = {40464500}, issn = {2768-6698}, mesh = {Humans ; *Lysophospholipids/metabolism ; *Nervous System Diseases/physiopathology/metabolism/drug therapy ; Animals ; Receptors, Lysophosphatidic Acid/metabolism ; Signal Transduction ; }, abstract = {Lysophosphatidic acid (LPA), a bioactive lipid molecule, has been identified as a critical regulator of several cellular processes in the central nervous system, with significant impacts on neuronal function, synaptic plasticity, and neuroinflammatory responses. While Alzheimer's disease, Multiple Sclerosis, and Parkinson's disease have garnered considerable attention due to their incidence and socioeconomic significance, many additional neurological illnesses remain unclear in terms of underlying pathophysiology and prospective treatment targets. This review synthesizes evidence linking LPA's function in neurological diseases such as traumatic brain injury, spinal cord injury, cerebellar ataxia, cerebral ischemia, seizures, Huntington's disease, amyotrophic lateral sclerosis, Hutchinson-Gilford progeria syndrome, autism, migraine, and human immunodeficiency virus (HIV)-associated complications Despite recent advances, the specific mechanisms underlying LPA's actions in various neurological disorders remain unknown, and further research is needed to understand the distinct roles of LPA across multiple disease conditions, as well as to investigate the therapeutic potential of targeting LPA receptors in these pathologies. The purpose of this review is to highlight the multiple functions of LPA in the aforementioned neurological diseases, which frequently share the same poor prognosis due to a scarcity of truly effective therapies, while also evaluating the role of LPA, its receptors, and signaling as promising actors for the development of alternative therapeutic strategies to those proposed today.}, } @article {pmid40457402, year = {2025}, author = {Nosratzehi, M and Nosratzehi, S and Keikha, M}, title = {Beyond recommendations: expanding the ethical discourse on AI-assisted academic writing.}, journal = {Advances in simulation (London, England)}, volume = {10}, number = {1}, pages = {31}, pmid = {40457402}, issn = {2059-0628}, abstract = {In response to Cheng et al.'s article on ethical recommendations for artificial intelligence (AI)-assisted academic writing, we propose an expanded ethical discourse to address the evolving role of AI in scholarly communication. While applauding the authors' foundational framework, we argue for greater disciplinary specificity, clearer thresholds for AI contribution, and broader consideration of systemic risks including linguistic bias, environmental impact, and corporate concentration. We advocate for the development of a graded typology of AI involvement, institution-led regulatory mechanisms, and integration of ethical AI use into editorial and research training practices. These enhancements are essential for building equitable, transparent, and sustainable AI governance in academic publishing.}, } @article {pmid40457369, year = {2025}, author = {Zangouei, Z and Amouzeshi, Z and Mohsenizadeh, SM and Ayati, R}, title = {The impact of self-care training using the teach-back method with telephone follow-up on adherence to treatment in patients with hypothyroidism: a randomized controlled clinical trial.}, journal = {BMC health services research}, volume = {25}, number = {1}, pages = {781}, pmid = {40457369}, issn = {1472-6963}, abstract = {BACKGROUND: Thyroid disorders represent a prevalent chronic disease category in the general population and become more prevalent with age. Adherence to treatment and regular follow-up are critical issues determining the recovery of these patients. The present study aimed to determine the impact of self-care training using the teach-back method combined with telephone follow-up on adherence to treatment in patients with hypothyroidism.

METHODS: A randomized controlled clinical trial was conducted in 2024. A total of 62 eligible patients with hypothyroidism visiting Vali-e-Asr Hospital, affiliated with Birjand University of Medical Sciences, were selected and randomly assigned to two groups. The intervention group members received self-care training using the teach-back method over two sessions, each lasting 45 to 60 min. The control group only received the routine care provided by the center. Data were collected using Fatemi et al.’s Adherence to Treatment Questionnaire and a demographic characteristics form. Data were analyzed using SPSS software version 23 and independent t-test, Mann-Whitney, Repeated measures ANOVA, Friedman non-parametric test, Fisher’s Exact test and chi-square test.

RESULTS: According to findings, 80.6% (n = 25) of the participants were women. The mean age of the intervention and the control group was 45.42 ± 15.74 and 43.97 ± 15.77 years, respectively, with no statistically significant difference (P = 0.72). The results showed a statistically significant difference in the mean overall adherence score (P < 0.001) and its components (P < 0.001) between the two groups. The effect size for all variables immediately and 2 months after the intervention, based on Cohen’s d formula, is greater than 0.80.

CONCLUSION: It seems that self-care training using the teach-back method has a significant impact on adherence to treatment in patients with hypothyroidism. Therefore, it is recommended to use teach-back method alongside other educational methods to enhance adherence to treatment in patients with hypothyroidism.

TRIAL REGISTRATION: Iranian Registry of Clinical Trials (IRCT20241125063855N1, Registration Date:22/12/2024).}, } @article {pmid40457309, year = {2025}, author = {Gupta, A and Wyatt, LC and Mammen, S and Zanowiak, JM and Lim, S and Islam, NS and Kumar, R and Beane, S and Gold, HT}, title = {Cost analysis of implementing a community health worker-led weight reduction randomized-controlled trial among prediabetic south asian patients at primary care sites in NYC.}, journal = {Implementation science : IS}, volume = {20}, number = {1}, pages = {26}, pmid = {40457309}, issn = {1748-5908}, support = {U48 DP001904/DP/NCCDPHP CDC HHS/United States ; UL1 TR001445/TR/NCATS NIH HHS/United States ; UL1TR0001445/TR/NCATS NIH HHS/United States ; 1UG3HL15310/HL/NHLBI NIH HHS/United States ; U48DP001904/CC/CDC HHS/United States ; 1U2CDK137135/DK/NIDDK NIH HHS/United States ; R01 MD018528/MD/NIMHD NIH HHS/United States ; R01DK110048-01A1/DK/NIDDK NIH HHS/United States ; R18DK110740/DK/NIDDK NIH HHS/United States ; R18 DK110740/DK/NIDDK NIH HHS/United States ; R01MD018528/MD/NIMHD NIH HHS/United States ; R01 DK110048/DK/NIDDK NIH HHS/United States ; U54MD000538/MD/NIMHD NIH HHS/United States ; }, mesh = {Humans ; *Community Health Workers/economics ; *Primary Health Care/economics ; *Prediabetic State/therapy/ethnology ; New York City ; *Weight Reduction Programs/economics/methods ; COVID-19/epidemiology ; Male ; Costs and Cost Analysis ; Female ; Middle Aged ; Weight Loss ; Cost-Benefit Analysis ; SARS-CoV-2 ; }, abstract = {BACKGROUND: We conducted a cost analysis of implementing a randomized controlled trial that proved the effectiveness of a community health worker (CHW) facilitated weight loss intervention among South Asian patients with prediabetes receiving care at primary care practices in New York City. South Asians have a high prevalence of diabetes, but no study to date has evaluated the cost of implementing an evidence-based lifestyle intervention in this population. Cost estimates are necessary for an intervention's adoption and scale-up.

METHODS: The first wave of the intervention was implemented in-person, followed by two waves implemented remotely during the COVID-19 pandemic. We estimated the implementation, intervention, and adaptation costs and the costs by each wave of implementation, by applying the Gold et al.'s economic framework and ERIC discrete implementation strategy compilation Costs were calculated from the perspective of a health care payer, public health agency, or health care system. The CHW intervention included group education sessions over six months. For each wave, we separately estimated the total cost, cost per practice, and cost when implemented at only one practice. Using the Bureau of Labor Statistics salary estimates, we calculated the national average (mean salary) and lower (25th percentile salary) and upper (75th percentile salary) bounds.

RESULTS: The average total 6-month implementation costs over 3 waves, each targeting seven practices was $215,420 (range: $158,620-$257,020). Program staff salaries comprised > 93% of total costs. Adaptation cost was nearly 1/3 of start-up costs. On average, implementation at one practice would cost twice as much as the per-practice costs when implemented simultaneously at seven practices in a wave, due to spread of start-up costs across multiple sites.

CONCLUSIONS: Staff salaries comprise most of the budget to implement such an intervention. It is most efficient for an agency to implement this intervention across several practices simultaneously. Decision-makers will need to evaluate relative costs and effectiveness of other options to achieve weight loss in a minority community with constrained resources.

CLINICALTRIALS: GOV: This study was registered on June 15, 2017 at  https://www.

CLINICALTRIALS: gov as NCT03188094. https://clinicaltrials.gov/ct2/show/NCT03188094 .}, } @article {pmid40456872, year = {2025}, author = {Pertek Hatipoğlu, F and Magat, G and Karobari, MI and Madarati, AA and Tulegenova, I and Hatipoğlu, Ö and Taha, N and Makahleh, N and Fernández-Grisales, R and Bekjanova, O and Rahimi, M and Donnermeyer, D and Madfa, AA and Petridis, X and Intriago, MG and Shah, T and Allawi, S and Ivica, A and Lim, WY and Hamouda, A and Jagtap, R and Martín-Biedma, B and Lehmann, AP and Alfirjani, S and Palma, PJ and Buchanan, GD}, title = {Root and canal configurations of maxillary first premolars in 22 countries using two classification systems: a multinational cross-sectional study.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {19290}, pmid = {40456872}, issn = {2045-2322}, mesh = {Humans ; Female ; Male ; Cross-Sectional Studies ; *Bicuspid/diagnostic imaging/anatomy & histology ; Adult ; *Tooth Root/diagnostic imaging/anatomy & histology ; Cone-Beam Computed Tomography ; *Maxilla/diagnostic imaging/anatomy & histology ; Adolescent ; Young Adult ; *Dental Pulp Cavity/diagnostic imaging/anatomy & histology ; Middle Aged ; }, abstract = {This study aimed to evaluate the root and root canal morphology of maxillary first premolars (M1Ps) globally using cone-beam computed tomography (CBCT), comparing results with Vertucci's and Ahmed et al.'s classification systems. CBCT images were obtained for various purposes such as orthodontic treatment planning, tooth impaction, implant surgery, and trauma cases. M1Ps were evaluated in three planes to determine root and root canal morphology, and root bifurcation levels were assessed using integrated software. Prevalence variations between countries and overall prevalence were analyzed using meta-analysis software. A total of 6,600 patients (13,200 bilateral M1Ps) were examined. According to Vertucci's classification, Type IV (59%), Type II (12%), Type I (9%), and Type III (8%) were the most common configurations. Based on Ahmed's classification,[2]MP B[1] P[1] was the most prevalent configuration (53%), followed by [1]MP[1] (9%),[1]MP[1-2-1] (8%), and [1]MP[2-1-1] (7%). The prevalence of [2]MP B[1] P[1] by gender revealed a pooled prevalence of 58% in males and 50% in females. No significant difference was found across age ranges (p > 0.05). Ahmed's classification system provided a more comprehensive analysis by successfully classifying all cases, whereas Vertucci's system failed to categorize 1.8-2.7% of the cases. Significant bilateral symmetry in root morphology was noted. There are regional and gender-specific differences in the root canal morphology of M1Ps. Ahmed et al.'s classification system was more comprehensive, effectively categorizing all observed morphologies compared to Vertucci's system, which had limitations and left some morphologies unclassified.}, } @article {pmid40454774, year = {2025}, author = {Madrer, N and Perera, ND and Uccelli, NA and Abbondanza, A and Andersen, JV and Carsana, EV and Demmings, MD and Fernandez, RF and de Fragas, MG and Gbadamosi, I and Kulshrestha, D and Lima-Filho, RAS and Marian, OC and Markussen, KH and McGovern, AJ and Neal, ES and Sarkar, S and Šimončičová, E and Soto-Verdugo, J and Yandiev, S and Fernández-Moncada, I}, title = {Neural Metabolic Networks: Key Elements of Healthy Brain Function.}, journal = {Journal of neurochemistry}, volume = {169}, number = {6}, pages = {e70084}, pmid = {40454774}, issn = {1471-4159}, mesh = {Humans ; *Brain/metabolism ; Animals ; *Nerve Net/metabolism ; *Energy Metabolism/physiology ; *Metabolic Networks and Pathways/physiology ; *Neurons/metabolism ; }, abstract = {Neural networks are responsible for processing sensory stimuli and driving the synaptic activity required for brain function and behavior. This computational capacity is expensive and requires a steady supply of energy and building blocks to operate. Importantly, the neural networks are composed of different cell populations, whose metabolic profiles differ between each other, thus endowing them with different metabolic capacities, such as, for example, the ability to synthesize specific metabolic precursors or variable proficiency to manage their metabolic waste. These marked differences likely prompted the emergence of diverse intercellular metabolic interactions, in which the shuttling and cycling of specific metabolites between brain cells allows the separation of workload and efficient control of energy demand and supply within the central nervous system. Nevertheless, our knowledge about brain bioenergetics and the specific metabolic adaptations of neural cells still warrants further studies. In this review, originated from the Fourth International Society for Neurochemistry (ISN) and Journal of Neurochemistry (JNC) Flagship School held in Schmerlenbach, Germany (2022), we describe and discuss the specific metabolic profiles of brain cells, the intercellular metabolic exchanges between these cells, and how these bioenergetic activities shape synaptic function and behavior. Furthermore, we discuss the potential role of faulty brain metabolic activity in the etiology and progression of Alzheimer's disease, Parkinson disease, and Amyotrophic lateral sclerosis. We foresee that a deeper understanding of neural networks metabolism will provide crucial insights into how higher-order brain functions emerge and reveal the roots of neuropathological conditions whose hallmarks include impaired brain metabolic function.}, } @article {pmid40446633, year = {2025}, author = {Sümer, N and Kahya, Y and Erel, S and Alsancak-Akbulut, C}, title = {A screening measure for infant attachment: The Turkish adaptation of the Brief Attachment Scale-16.}, journal = {Infant behavior & development}, volume = {80}, number = {}, pages = {102074}, doi = {10.1016/j.infbeh.2025.102074}, pmid = {40446633}, issn = {1879-0453}, abstract = {Considering the need for a brief but valid screening measure for infant attachment, we aimed to examine the psychometric quality of Cadman et al.'s (2018) Brief Attachment Scale-16 (BAS-16) in Turkish mother-child samples. The validity of the BAS-16 Turkish was examined in two independent samples based on its associations with well-established constructs of attachment security and maternal sensitivity, child adjustment, and temperament measures, namely, the Attachment Q-Set (AQS), the Maternal Behavior Q-Set (MBQS), the Child Behavior Checklist (CBCL), the Emotionality, Activity, Sociability Temperament Survey (EAS), respectively. The results of Study 1 and Study 2 supported the two-factor structure of BAS-16 Turkish. In Study 1, the BAS-16 Turkish total scores were significantly associated with the AQS security and MBQS sensitivity scores, and marginally with child externalizing problems but not with child temperament. In Study 2, aiming to cross-validate the findings of Study 1, the BAS-16 Turkish total and subscale scores strongly correlated with the AQS security scores; the BAS-16 Turkish total and Harmonious Interaction (HI) subscale scores were related to the MBQS sensitivity scores. In both samples, regression analyses showed that maternal sensitivity significantly predicted the BAS-16 Turkish total score above and beyond the effects of demographic characteristics and temperament. The findings from two studies suggest that the BAS-16 has adequate validity in assessing infant/child attachment in Turkish samples, representing a non-WEIRD cultural context, and can be used as a practical screening tool.}, } @article {pmid40444996, year = {2025}, author = {Lunnay, B and MacLean, S and Hughes, T and Pennay, A and Ward, PR}, title = {'Moderation Is the Holy Grail': The Acceptability of 'Sober Curious' Tools for Alcohol Reduction Among Midlife Women.}, journal = {Drug and alcohol review}, volume = {44}, number = {5}, pages = {1496-1507}, doi = {10.1111/dar.14085}, pmid = {40444996}, issn = {1465-3362}, support = {//Flinders Foundation/ ; }, mesh = {Humans ; Female ; Middle Aged ; *Alcohol Drinking/psychology/prevention & control ; Australia ; Qualitative Research ; *Patient Acceptance of Health Care/psychology ; }, abstract = {INTRODUCTION: Midlife Australian women are a population group in which alcohol consumption is not decreasing across generations, as in other groups. We explored midlife women's perceptions and experiences of engaging with sober curious tools (self-guided programs, apps, literature, podcasts, online forums) to determine the acceptability of such tools among those seeking to reduce drinking.

METHOD: Qualitative interviews with 26 Australian women (aged 45-64) of varying social classes, work and relationship statuses living in Adelaide/Melbourne/Sydney who self-reported heavy/medium drinking during 2021. We applied Sekhon et al.'s 'acceptability of healthcare interventions' framework to understand components that increase the acceptability of sober curious tools and an abductive logic to explain the mechanisms that impact acceptability.

RESULTS: Acceptability was stronger among women who felt a sense of security and belonging when tools cohered with their preparedness to reduce drinking and accounted for their perceptions about feasible reductions. Importantly, sober curious tools increased the acceptability of reducing alcohol by increasing women's agency to 'question' heavy-drinking norms, especially when combined with social supports. It is important to women that they envisage themselves as the intended 'user' of sober curious tools. Acceptability differed for women based on social class inequities that result in marginalisation and that intersect with stigma because of ageism.

DISCUSSION AND CONCLUSIONS: Sober curious tools are most acceptable to middle class and affluent women and represent capacities to reduce alcohol consumption. Understanding the experiences of diverse groups of women and their agency to engage with sober curiosity is important to inform future interventions.}, } @article {pmid40444312, year = {2025}, author = {Noble, FJ and Lahane, ST and Lahane, TP and Parekh, RH and Lahane, ST and Dhaytadak, PP and Jain, AK}, title = {Validation of ocular trauma score (OTS) in open- and closed-globe injuries in Indian patients.}, journal = {Indian journal of ophthalmology}, volume = {73}, number = {Suppl 3}, pages = {S498-S501}, pmid = {40444312}, issn = {1998-3689}, mesh = {Humans ; Male ; Female ; India/epidemiology ; Prospective Studies ; Adult ; *Visual Acuity ; Middle Aged ; Young Adult ; Adolescent ; *Eye Injuries, Penetrating/diagnosis/epidemiology ; *Wounds, Nonpenetrating/diagnosis/epidemiology ; Child ; *Eye Injuries/epidemiology/diagnosis ; Follow-Up Studies ; Predictive Value of Tests ; Child, Preschool ; Reproducibility of Results ; }, abstract = {PURPOSE: To validate the predictive value of the ocular trauma score (OTS) in open- and closed-globe eye injuries in the Indian context.

DESIGN: Prospective interventional case series.

METHODS: This study, conducted at a tertiary healthcare institute from January 2018 to June 2019, included 150 eyes of 150 patients with open- and closed-globe injuries. Inclusion criteria were patients with globe injuries who provided informed consent and had complete OTS data. Exclusion criteria included electric, chemical, and thermal injuries, prior surgery, pre-existing poor visual acuity (VA), and severe systemic injuries. There was no randomization. Demographic details, initial and final VA, injury type, and OTS variables were recorded. Patients were classified into OTS categories preoperatively based on Kuhn et al.'s system, and VA distribution was compared with the original study. The main outcome was to assess the correlation between the final BCVA at 6 months post-intervention and the predicted VA based on the OTS category.

RESULTS: A total of 150 patients (72% open globe, 28% closed globe) were included, with a male-to-female ratio of 4.5:1. The mean age ± SD was 29.34 ± 17.49 years. OTS classification showed 6% in OTS 1, 17% in OTS 2, 67% in OTS 3, 4% in OTS 4, and 6% in OTS 5. Final VA was ≤20/40 (41%), 20/50-20/200 (20%), 20/200-1/200 (15%), HM/PL (15%), and NLP (9%). Final VA post-treatment correlated with predicted VA as per the OTS category (Spearman's r = 0.53, P < 0.001).

CONCLUSION: OTS provides reliable prognostic information and has fair predictive value for final VA in open- and closed-globe injuries.}, } @article {pmid40440110, year = {2025}, author = {Dong, J and Liu, H}, title = {When predictors sum to a constant: Trade-off effect analysis using a regression model based on isometric log-ratio transformation.}, journal = {Psychological methods}, volume = {}, number = {}, pages = {}, doi = {10.1037/met0000668}, pmid = {40440110}, issn = {1939-1463}, support = {//National Natural Science Foundation of China/ ; }, abstract = {The standard regression model is not feasible when the sum of predictors is a constant, which is a common occurrence in proportional data or ipsative data. Davison et al. (2022) described a set of reduced-rank regression models in which each regression coefficient can be interpreted as a predictor trade-off effect. However, the assumption of linearity and symmetry in their method is too rigid, and the compositional nature of the predictors should not be disregarded. In this article, from the perspective of compositional data, a new method named isometric-log-ratio-transformed trade-off effect analysis (ITEA) is proposed. The predictors are transformed into isometric log-ratio coordinates using a planned sequential binary partition, and trade-off effects are then estimated using a regression model with isometric log-ratio coordinates. Instead of directly relying on regression coefficients, the trade-off effect is defined as the difference in the dependent variable before and after the trade-off, from which the 95% confidence interval can be further derived. Moreover, the main results of the ITEA are not affected by the variation in orthonormal bases. Applying the ITEA to the data in Davison et al.'s (2022) study yields more flexible and interpretable results of trade-off effects. We also provide an empirical example of a forced-choice questionnaire to verify the validity of the ITEA, with visualization attempts of trade-off effects under different conditions. Usefulness, suitable applications, and potential extensions are discussed. (PsycInfo Database Record (c) 2025 APA, all rights reserved).}, } @article {pmid40436909, year = {2025}, author = {Subbiah, V}, title = {Tissue-agnostic cancer therapies: promise, reality, and the path forward.}, journal = {Nature communications}, volume = {16}, number = {1}, pages = {4972}, pmid = {40436909}, issn = {2041-1723}, abstract = {Tissue-agnostic cancer therapies promise to revolutionize oncology by targeting molecular drivers. Sledge et al.’s study of nearly 300,000 tumors found 21.5% with tissue-agnostic indications. Despite nine FDA approvals, real-world implementation challenges persist. Progress depends on universal genomic testing, an oncogenomic-savvy workforce, innovative trials, updated regulations, and real-world evidence to maximize potential.}, } @article {pmid40428895, year = {2025}, author = {Meļņikova, V and Timčenko, M and Bērziņa, S and Karelis, G}, title = {Can Antidromic and Orthodromic Stimulation Both Be Used for Correct Carpal Tunnel Syndrome Staging by J. D. Bland and L. Padua?.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {61}, number = {5}, pages = {}, pmid = {40428895}, issn = {1648-9144}, mesh = {Humans ; *Carpal Tunnel Syndrome/diagnosis/physiopathology/classification ; Female ; Male ; Middle Aged ; Neural Conduction/physiology ; Adult ; Aged ; ROC Curve ; Median Nerve/physiopathology ; *Electric Stimulation/methods ; Action Potentials/physiology ; Sensitivity and Specificity ; Severity of Illness Index ; }, abstract = {Background and Objectives: Padua (1997) and Bland (2000) have already proposed neurophysiological classification scales for patients with carpal tunnel syndrome (CTS), where the absence of orthodromic sensory response is used as a criterion of a severe stage. We hypothesized that antidromic values cannot be used equally for correct staging. Materials and Methods: We performed a consecutive investigation with nerve conduction studies in 60 arms of patients with CTS and prolonged distal motor latency. Results: In 11 out of 60 arms (18.3% of cases), orthodromic sensory nerve action potential (SNAP) was undetectable, while the antidromic SNAP was present. ROC curve analysis with Yoden index calculation were utilized in the study. The cut-off value of antidromic SNAP amplitude as a diagnostic marker of unrecordable orthodromic SNAP was 3.9 µV with high sensitivity and specificity. Conclusions: Our findings conflict with Padua et al.'s assertion that CTS staging can be determined irrespective of the stimulation technique. Antidromic SNAP amplitude is the most reliable parameter for predicting the absent orthodromic SNAP. Our study addresses the bias associated with the application of antidromic stimulation of median nerve sensory fibers for accurately staging moderate to severe CTS.}, } @article {pmid40426065, year = {2025}, author = {Schantz, C and Gnangnon, FHR and Aboubakar, M and Agbodande, AK and Puig, P and Denakpo, JL and Tonato Bagnan, A and Bottin, M and Agbodjavou, KM and Sacca, HR and Teixeira, L and Ridde, V and , }, title = {Barriers and opportunities related to access to oncology care in Benin: a qualitative study on breast cancer.}, journal = {BMC cancer}, volume = {25}, number = {1}, pages = {947}, pmid = {40426065}, issn = {1471-2407}, support = {DA N°2022-135 SCHANTZ//Institut National Du Cancer/ ; ANR-17- CONV-0001//French Collaborative Institute on Migration/ ; IdEx University of Paris, ANR-18-IDEX-0001//Cité du Genre/ ; }, mesh = {Humans ; Female ; Benin/epidemiology ; *Breast Neoplasms/therapy/diagnosis/epidemiology ; *Health Services Accessibility ; Qualitative Research ; Middle Aged ; Adult ; Aged ; Palliative Care ; *Medical Oncology ; }, abstract = {BACKGROUND: Breast cancer is the most prevalent cancer among women globally, including in Africa. Oncology is a relatively new discipline in many West African countries, particularly in Benin. There is currently a lack of data concerning the current state of cancer care infrastructure and oncology practices within these countries. The aim of the article is to describe the barriers and opportunities related to access to oncology care in Benin.

METHODS: We employed a qualitative research design. Fifty-six semi-structured interviews were conducted with caregivers treating cancer (n=26), women with breast cancer (n=23), and representatives of associations (n=2). Additionally, 18 days of participant observation were conducted in a chemotherapy and palliative care departments in Cotonou, Benin. The data was analysed using Levesque et al.'s theoretical framework on access to healthcare.

RESULTS: Women encounter obstacles such as delayed diagnosis and unequal access to information, as well as socio-cultural beliefs that favour traditional medicine and discourage surgical interventions like mastectomy. The treatment pathway is often chaotic due to insufficient specialised caregivers and limited infrastructure, with services centralised in Cotonou forcing patients to travel long distances around the country. The current lack of radiotherapy requires patients in need to travel abroad for treatment. High costs of biomedical tests and treatments often lead to care abandonment, worsening health inequalities. However, positive changes should be highlighted, such as the establishment of the Inter-University Diploma in Gynaecological and Breast Oncology in 2013, the expansion of palliative care services in the country, and the planned opening of the Calavi International Hospital Centre in 2025. Challenges include continuing to train health professionals in oncology, further developing health financing and supporting civil society to raise awareness of breast cancer.

CONCLUSIONS: Benin is facing several challenges in relation to the provision of timely and high-quality care for women with breast cancer. However, there is a growing commitment to enhancing breast cancer care in Benin.}, } @article {pmid40422459, year = {2025}, author = {You, Q and Yang, H and Zhang, X and Jiang, X and Guo, K and Hu, K}, title = {Forensic Support for Abraham et al.'s BB Protocol.}, journal = {Entropy (Basel, Switzerland)}, volume = {27}, number = {5}, pages = {}, pmid = {40422459}, issn = {1099-4300}, support = {2022YFB2701600//National Key Research and Development Program of China/ ; }, abstract = {The consensus protocol is a fundamental building block in distributed computing and has been widely used in blockchain systems in recent years. Paxos, introduced by Lamport, stands out as one of the most widely adopted consensus protocols and has found application in renowned distributed systems, including Google's Spanner system. Abraham et al. analyzed the FaB Paxos protocol, a Byzantine version of Paxos. They abstracted the single-shot FaB Paxos into a Byzantine broadcast protocol and further gave an enhanced protocol known as Abraham et al.'s BB. Abraham et al.'s BB protocol achieved optimal two-round message interaction under good conditions, satisfying the optimal fault tolerance threshold of n=5t-1 where n represents total number of nodes in the system and t denotes the tolerable number of Byzantine nodes. This paper delves into scenarios wherein the actual number of Byzantine nodes surpasses the fault tolerance threshold during the operation of Abraham et al.'s BB protocol. To address this, we propose a forensic protocol designed to offer forensic support in cases of agreement violations. The forensic protocol aims to label Byzantine nodes through irrefutable evidence. We analyze the forensic protocol, elucidating the number of Byzantine nodes that the forensic protocol can label under different circumstances, along with the corresponding number of required messages. Additionally, we present an impossibility result, indicating that forensic support for Abraham et al.'s BB is impossible when the number of Byzantine nodes exceeds 2t-2.}, } @article {pmid40421202, year = {2025}, author = {Giusti, S and Susca, M and Cerulli, S and De Fenu, E and Adriani, E}, title = {Donor-Site Morbidity in Anterior Cruciate Ligament (ACL) Reconstruction With All-Soft Tissue Quadriceps Tendon Autograft vs. Hamstring Tendon Autograft: A Retrospective Monocentric Observational Study.}, journal = {Advances in orthopedics}, volume = {2025}, number = {}, pages = {8833546}, pmid = {40421202}, issn = {2090-3464}, abstract = {Background: Graft choice, together with operative technique, remains the most controversial topic surrounding ACL reconstruction. The ideal graft choice should recreate normal anatomy and biomechanics, allow for rapid return to play and have minimal harvest-site morbidity. The purposes of this study were to compare donor-site morbidity in all-soft-tissue quadriceps autograft vs. hamstring autografts based on Hacken et al.'s ACL Donor-Site Morbidity Questionnaire (32,587,874) and to assess the role played by external factors such as sex, mood, activity level and smoking status. Materials and Methods: We performed a retrospective analysis of our patients' records to identify individuals who were 30 years old or younger at the time of surgery and underwent ACL reconstruction using the anteromedial portal technique, without any additional treatments for ligament or meniscal injuries. At 12 months postintervention, donor-site morbidity was evaluated using the ACL donor-site morbidity questionnaire by Hacken et al. (2020). Analyses were performed using Jamovi freeware Version 2.3.19.0 (the Jamovi project, 2021). Independent samples t-test with Cohen's d as the effects' size statistics were used to compare donor-site morbidity and functional outcomes. Results: Significant differences between quadriceps tendon (QT) and STG groups were found for ACL donor-site morbidity questionnaire total score, numbness, size of numbness and muscle atrophy, all in favour of the QT cohort. Weak associations were found between female sex and low mood, both negatively impacting the reported donor site morbidity. No statistically significant differences were found for functional outcomes. Conclusion: ACL reconstruction with all-soft-tissue QT autograft showed overall superior donor-site morbidity outcomes when compared with HT autograft. Statistically significant results were also found in favour of QT when comparing numbness and size of numbness at the donor site and self-perceived muscle atrophy. Female sex and low mood have been found to impact donor-site morbidity negatively although larger samples are necessary to confirm this association. Graft choice in ACL reconstruction should always remain an individualized choice, but QT should be considered an equal, if not superior, alternative to other autologous autografts when comparing donor-site morbidity. Trial Registration: CINECA: 6458.}, } @article {pmid40420117, year = {2025}, author = {Phelan, H and Hassan, A and MacFarlane, A}, title = {The role of music and singing as research methods to improve migrants' involvement in health research and policy-making.}, journal = {Health research policy and systems}, volume = {23}, number = {1}, pages = {67}, pmid = {40420117}, issn = {1478-4505}, support = {NF-2021-Strand1a//Irish Research Council/ ; NF-2022-39186433//Irish Research Council/ ; IRPPI-2023-001//Health Research Board and Irish Research Council funded National PPI Ignite Network, Ireland/ ; }, mesh = {Humans ; Community-Based Participatory Research ; *Health Policy ; Health Services Research ; *Music ; *Policy Making ; Public Health ; Research Design ; *Singing ; *Transients and Migrants ; }, abstract = {This commentary explores the potential of arts-based research methods, particularly music and singing, to address issues of participatory inequity and the structural bias this creates in health research systems and policies. Focusing on migration as a pressing public health issue in resettlement countries in the Global North, this commentary's objective is to investigate the use of such creative methods as a means of improving migrants' participation in health research, knowledge translation and the development of health policy. In doing so, it challenges the overreliance on cognitively and verbally oriented methods in the Global North, which fail to harness the participatory potential of the whole-body sensorium. Drawing on Palmer et al.'s explanatory theoretical model of change and centralizing the concept of participatory space, it advances this discussion within a participatory health research paradigm. The exploration is further informed by a recent scoping review on the use of music as an arts-based method in migrant health research, as well as two case studies using the Irish World Music Café method. It concludes with the proposal that further exploration of music and singing as mechanisms of change in health research is essential if we are to fully understand whether/how music and singing for participatory space-making may reset the health research agenda, putting meaningful, whole-person engagement at the heart of research to inform systems and policies.}, } @article {pmid40418725, year = {2025}, author = {Letley, C and Kritzer, I and Sakuma, Y and Conyers, H and Randazzo, S and Ong, JJ and Day, S and Wu, D and Terris-Prestholt, F and Tucker, JD and Kpokiri, EE}, title = {Barriers and facilitators to accessing sexual health services among middle-aged and older adults in the UK, including those with disabilities: a qualitative analysis.}, journal = {Sexual health}, volume = {22}, number = {}, pages = {}, doi = {10.1071/SH24093}, pmid = {40418725}, issn = {1449-8987}, mesh = {Humans ; *Health Services Accessibility ; Male ; Middle Aged ; Female ; *Persons with Disabilities/psychology ; Qualitative Research ; Aged ; United Kingdom ; *Sexual and Gender Minorities/psychology ; *Sexual Health ; Social Stigma ; England ; *Reproductive Health Services ; Interviews as Topic ; }, abstract = {Background Middle-aged and older adults have unmet sexual health needs but often encounter challenges in accessing sexual health services (SHS). Individual, social, and environmental issues discourage middle-aged and older adults from accessing SHS. This study aimed to examine the barriers and facilitators experienced by middle-aged and older adults when accessing SHS in the UK. We included disabled people and sexual minorities with intersectional needs. Methods We organised semi-structured interviews with residents in England aged 45 years and older, including disabled people and sexual minorities. Participants were recruited using social media, primary care clinics, and community-based organisations. Interviews were audio-recorded and transcribed. Levesque et al .'s framework of healthcare access was used as a theoretical guide for analysing and presenting the study findings. After initial coding and theme generation, sub-themes of barriers and facilitators were mapped onto the healthcare access framework. Results The mean age of the 22 participants was 59years with 15 men and 7 women. Participants included people of different ethnicities (White British, Black African, and White mixed), disabilities, and sexualities. These participants highlighted various barriers to accessing SHS. Physical obstacles, such as narrow corridors, were cited as significant hindrances, although accommodations, such as physical assistance, were noted to enhance accessibility. Additionally, participants noted the pervasive stigma surrounding sexual health in older adults, exacerbated by healthcare providers presuming asexuality within this demographic. To address these multi-faceted challenges, greater involvement of disabled older individuals in the design of SHS is advocated. This collaborative approach is believed to expedite the development of age-responsive clinical services, fostering inclusivity and accessibility while simultaneously addressing psychological and social barriers. Conclusions Our data suggest that physical inaccessibility and stigma are persistent barriers to accessing SHS for older disabled people. Increasing training for healthcare providers, further research, and supportive policies are needed to improve delivery and access to SHS for older adults, including those with disabilities in the UK.}, } @article {pmid40413932, year = {2025}, author = {Nuryana, Z and Herdian, }, title = {Addressing the policy gap between adolescent mental health and school systems in indonesia.}, journal = {Asian journal of psychiatry}, volume = {109}, number = {}, pages = {104543}, doi = {10.1016/j.ajp.2025.104543}, pmid = {40413932}, issn = {1876-2026}, mesh = {Humans ; Indonesia ; Adolescent ; *Health Policy/legislation & jurisprudence ; *Mental Health ; *Adolescent Health ; *Adolescent Health Services/legislation & jurisprudence ; *School Health Services ; *Mental Disorders/therapy ; *School Mental Health Services ; *Mental Health Services ; }, abstract = {Adolescent mental health remains an under-addressed priority in national policies across Southeast Asia, including Indonesia. Although mental health legislation and adolescent health programs exist, integration within the school system is limited and inconsistent with international standards. This commentary builds on Mudunna et al.'s regional policy review by highlighting the critical gap in Indonesia's cross-sectoral coordination between health and education. Drawing on recent national data, we underscore the urgency of school-based mental health interventions in Indonesia, where prevalence rates of anxiety, depression, and suicidal ideation among adolescents are high, yet treatment access remains alarmingly low. We argue that adolescence must be understood not only as a period of psychological vulnerability but also as a transformative stage shaped by biological, social, and legal factors. In the context of LMICs like Indonesia, policy development must consider rights-based, participatory, and culturally appropriate approaches. We call for context-specific frameworks to embed mental health within the national education system as an essential investment in Indonesia's youth and national development.}, } @article {pmid40413335, year = {2025}, author = {Enichen, EJ and Heydari, K and Li, B and Kvedar, JC}, title = {Platform matters -- Differences in COVID data collected from Android and iOS app users.}, journal = {NPJ digital medicine}, volume = {8}, number = {1}, pages = {307}, pmid = {40413335}, issn = {2398-6352}, abstract = {Winter et al.’s recent investigation, “A Comparison of Self-Reported COVID-19 Symptoms Between Android and iOS CoronaCheck App Users,” reveals differences in the demographics and COVID-19 symptoms reported by users of Android and iOS systems. These findings not only provide more information about the varied experiences of individuals during the COVID-19 pandemic but also suggest that conclusions reached in studies using one operating platform may not be generalizable to users of other platforms.}, } @article {pmid40411403, year = {2025}, author = {Cheung, K and Ehrenkranz, R and Hinkle, JT and Yaden, DB}, title = {Commentary: A framework for assessment of adverse events in psychedelic research.}, journal = {Journal of psychopharmacology (Oxford, England)}, volume = {39}, number = {5}, pages = {431-433}, doi = {10.1177/02698811241309623}, pmid = {40411403}, issn = {1461-7285}, mesh = {*Hallucinogens/adverse effects ; Humans ; Research Design ; Clinical Trials as Topic/methods ; }, abstract = {Recent discussions about the methodological rigor of psychedelic clinical trials have focused on potential underreporting or misreporting of adverse events (AEs), with many calling for their systematic assessment to help mitigate these issues. In their recent paper, Palitsky et al. offer a comprehensive framework for the assessment of AEs in psychedelic-assisted therapies, with consideration of the spiritual, existential, religious, and theological impacts that psychedelics can have. In this commentary, we respond to Palitsky et al.'s proposal, discussing the framework, its feasibility, and various assessment methods. We emphasize the need to ensure that AE assessment in psychedelic clinical trials is held to the same rigor and standard as research in other areas, in addition to maintaining and improving transparency and accessibility in AE reporting.}, } @article {pmid40400560, year = {2025}, author = {Evans-Mitchell, GS and Sacca, L and Markham, C and Schultz, K and McCurdy, S and Tingey, L and Peskin, MF}, title = {A Systematic Review of Trauma-Informed Sexual Health Education Interventions for Adolescents and Young Adults Within the United States and Canada.}, journal = {International journal of sexual health : official journal of the World Association for Sexual Health}, volume = {37}, number = {2}, pages = {198-208}, pmid = {40400560}, issn = {1931-762X}, abstract = {OBJECTIVE: To systematically identify and critically examine trauma-informed sexual health education interventions developed for adolescents and young adults and describe how they integrate key principles of a trauma-informed approach.

METHODS: Using the Preferred Reporting Items for Systematic review and Meta-Analysis Protocols (PRISMA-P) guidelines, Substance Abuse and Mental Health Services Administration (SAMHSA) principles, and Khan et al.'s review methodology, we reviewed sexual health intervention studies described as trauma-informed published between 2014 and 2023 within the United States and Canada.

RESULTS: The review found three interventions integrated five to six aspects of a trauma-informed approach relative to Kahn's definition and SAMHSA's principles.

CONCLUSIONS: Based on the limited number of trauma-informed interventions being identified, this highlights a continuation of the gap in trauma-informed sexual health interventions.}, } @article {pmid40399048, year = {2025}, author = {Komatsu, T and Kawai, Y and Takayama, Y and Akamada, Y and Miyagawa, M and Ikeda, M and Tsumura, H and Ishii, D and Matsumoto, K and Iwamura, M and Okamoto, H and Hanaki, H and Otori, K}, title = {External Validation of Population Pharmacokinetic Models for Unbound Cefazolin in Patients Receiving Prophylactic Dosing.}, journal = {Biological & pharmaceutical bulletin}, volume = {48}, number = {5}, pages = {650-656}, doi = {10.1248/bpb.b25-00027}, pmid = {40399048}, issn = {1347-5215}, mesh = {*Cefazolin/pharmacokinetics/administration & dosage ; Humans ; *Anti-Bacterial Agents/pharmacokinetics/administration & dosage/blood ; *Models, Biological ; *Antibiotic Prophylaxis ; }, abstract = {This study aimed to evaluate published population pharmacokinetic models of unbound cefazolin to assess their predictive performance using an independent dataset. A systematic literature search was conducted on PubMed to identify studies evaluating the population pharmacokinetics of unbound cefazolin in patients. Subsequently, the selected models were used for external validation. Predictive bias was visually assessed by plotting the prediction errors (PEs) and relative PEs. Predictive precision was evaluated by calculating the mean absolute error (MAE), root mean square error (RMSE), and mean relative error (MRE). The predictive performance of the 4 unbound population pharmacokinetic models was evaluated using clinical data from 64 patients and 218 unbound concentration samples. The PEs for unbound cefazolin concentrations in the Komatsu model indicated a positive bias, while the RPEs demonstrated similar predictive distributions along the y = 0 line, regardless of the predicted values. In contrast, the other 3 models showed a negative bias for both PE and RPE at unbound cefazolin concentrations. The best MAE, RMSE, and MRE (%) values were 4.71, 9.02, and 30.2 in Komatsu et al.'s model, while the next best values were 11.5, 16.1, and 107.2 in Chung et al.'s model. Both models, which performed best regarding bias and accuracy, were also utilized in studies on unbound concentrations and the correlation between total concentrations and protein-binding sites. This study identified these models as the most suitable for predicting unbound cefazolin concentration profiles in surgical patients.}, } @article {pmid40398684, year = {2025}, author = {Naufal, E and Shadbolt, C and Wouthuyzen-Bakker, M and Rele, S and Sahebjada, S and Thuraisingam, S and Babazadeh, S and Choong, PF and Dowsey, MM}, title = {Clinical prediction models to guide treatment of periprosthetic joint infections: a systematic review and meta-analysis.}, journal = {The Journal of hospital infection}, volume = {162}, number = {}, pages = {53-61}, doi = {10.1016/j.jhin.2025.04.035}, pmid = {40398684}, issn = {1532-2939}, mesh = {Humans ; *Prosthesis-Related Infections/therapy ; }, abstract = {BACKGROUND: Several clinical prediction models that aim to guide decisions about the management of periprosthetic joint infections (PJIs) have been developed. While some models have been recommended for use in clinical settings, their suitability remains uncertain.

METHODS: We systematically reviewed and critically appraised all multi-variable prediction models for the treatment of PJI. We searched MEDLINE, EMBASE, Web of Science, and Google Scholar from inception until 1[st] March 2024 and included studies that developed or validated models that predict the outcome of PJI. We used PROBAST (Prediction model Risk Of Bias ASsessment Tool) to assess the risk of bias and applicability. Model performance estimates were pooled via random effect meta-analysis.

RESULTS: Thirteen predictive models and seven external validations were identified. Methodological issues were identified in all studies. Pooled estimates indicated that the KLIC (Kidney, Liver, Index surgery, Cemented prosthesis, C-reactive protein) score had fair discriminative performance (pooled c-statistic 0.62, 95% CI 0.55-0.69). Both the τ[2] (0.02) and I[2] (33.4) estimates indicated that between-study heterogeneity was minimal. Meta-analysis indicated Shohat et al.'s model had good discriminative performance (pooled c-statistic 0.74, 95% CI 0.57-0.85). Both the τ[2] (0.0) and I[2] (0.0) indicated that between study heterogeneity was minimal.

CONCLUSIONS: Clinicians should be aware of limitations in the methods used to develop available models to predict outcomes of PJI. As no models have consistently demonstrated adequate performance across external validation studies, it remains unclear whether any available models would provide reliable information if used to guide clinical decision making.}, } @article {pmid40395863, year = {2025}, author = {Ikeda, S and Sudo, K and Iwamoto, A and Kanda, M and Aoyagi, R and Ota, S and Shakya, M and Nii, M and Sawada, T and Nakasa, T and Fujita, M}, title = {A critical role of navigator for vulnerable migrants in health emergency: overcoming administrative barriers to COVID-19 vaccination in Japan.}, journal = {Journal of migration and health}, volume = {11}, number = {}, pages = {100332}, pmid = {40395863}, issn = {2666-6235}, abstract = {INTRODUCTION: Migrants face significant barriers in accessing healthcare, particularly during public health emergencies such as the COVID-19 pandemic. In Japan, the residency-based healthcare system posed administrative challenges for migrants, especially undocumented individuals, in obtaining vaccination vouchers-a prerequisite for receiving COVID-19 vaccines. The COVID-19 Vaccination Information Center for International Citizens (COVIC) was established to bridge this gap by offering multilingual support and direct casework assistance.

METHODS: This study employed a case study design, analyzing 275 inquiries involving 418 migrants who sought assistance from COVIC between September 2021 and March 2022. Using Castañeda et al.'s framework on migration and health, administrative barriers were examined, and COVIC's role as a navigator was evaluated. Descriptive statistics were used to assess COVIC's impact on vaccine access.

RESULTS: The majority of migrants seeking assistance (38.5 %) were undocumented, and 91.3 % of them lacked a vaccination voucher before contacting COVIC. The intervention facilitated voucher issuance for 73.8 % of migrants who inquired about it. While COVIC successfully helped all short-term and mid-to-long-term residents obtain vouchers, only 54.2 % of undocumented migrants were able to receive one, reflecting persistent systemic exclusions.

CONCLUSION: COVIC played a crucial role in mitigating administrative barriers, yet structural limitations prevented full healthcare access for undocumented migrants. These findings underscore the need for standardized administrative policies, integrated navigator programs, and inclusive healthcare strategies to enhance equitable access for migrant populations in future health crises.}, } @article {pmid40393206, year = {2025}, author = {Fatima, A and Adnan, M and Hussain Bakhtiari, MI}, title = {Anti-NMDAR encephalitis and MOGAD - Clinical and treatment insights.}, journal = {Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia}, volume = {137}, number = {}, pages = {111333}, doi = {10.1016/j.jocn.2025.111333}, pmid = {40393206}, issn = {1532-2653}, mesh = {Humans ; *Anti-N-Methyl-D-Aspartate Receptor Encephalitis/therapy/complications/drug therapy ; Autoantibodies/immunology ; *Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease ; Rituximab/therapeutic use ; }, abstract = {This letter responds to Yan et al.'s study on anti-NMDAR encephalitis combined with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), highlighting its valuable findings on clinical features, MRI lesion diversity, high relapse rates, and rituximab's efficacy in reducing recurrence. We emphasize limitations including reliance on the modified Rankin Scale, which overlooks cognitive and psychosocial impairments, advocating for comprehensive neuropsychological and quality-of-life assessments in future research. The absence of control groups limits comparison to isolated NMDARE or MOGAD cases. Additionally, we propose that the observed high cortical encephalitis rate may reflect additive rather than synergistic effects of both antibodies, given that cortical involvement is known in each condition independently. Further studies should clarify these mechanisms to improve understanding and management of this complex overlap syndrome.}, } @article {pmid40389744, year = {2025}, author = {El-Masry, H and Abouegylah, M and Abokhozima, A}, title = {Critical Aspects into Surgical Management, Classification, and Therapeutic Guidelines for Incidental GISTs During Bariatric Surgeries.}, journal = {Obesity surgery}, volume = {35}, number = {7}, pages = {2762-2764}, pmid = {40389744}, issn = {1708-0428}, mesh = {Humans ; Incidental Findings ; *Bariatric Surgery ; *Gastrointestinal Stromal Tumors/surgery/classification/pathology/diagnosis ; *Obesity, Morbid/surgery/complications ; Practice Guidelines as Topic ; *Gastrointestinal Neoplasms/surgery/classification/diagnosis ; }, abstract = {Incidental gastrointestinal stromal tumors (GISTs) discovered during bariatric surgeries present unique diagnostic and management challenges. In response to Khan et al.'s report on a sleeve-preserving approach to GIST resection, we highlight several critical considerations. Contrary to the notion that incidental GISTs rarely alter surgical plans, tumor characteristics, especially size and location near critical structures like the gastroesophageal junction, can necessitate procedural modifications. Preoperative endoscopy plays a pivotal role in early detection and surgical planning. We also underscore the importance of individualized oncologic decision-making, integrating tumor parameters and procedural classification systems.}, } @article {pmid40383754, year = {2025}, author = {Heidari, N and Ghannadzadeh Kermani Pour, R and Farshbafnadi, M and Heidari, A and Ghane, Y}, title = {A systematic review of tumor necrosis factor-α blockers, anti-interleukins, and small molecule inhibitors for dissecting cellulitis of the scalp treatment.}, journal = {Orphanet journal of rare diseases}, volume = {20}, number = {1}, pages = {236}, pmid = {40383754}, issn = {1750-1172}, mesh = {Humans ; *Cellulitis/drug therapy ; *Scalp/pathology/drug effects ; *Scalp Dermatoses/drug therapy ; *Skin Diseases, Genetic/drug therapy ; *Tumor Necrosis Factor-alpha/antagonists & inhibitors ; }, abstract = {BACKGROUND: Dissecting cellulitis of the scalp (DCS) is a type of neutrophilic scarring alopecia identified by the development of folliculitis with clusters of perifollicular pustules and then progresses to abscesses and intercommunicating sinus formation. In the absence of evidence-based guidelines, the treatment of DCS remains a therapeutic challenge. Our study aimed to assess the safety and efficacy of biologics, including tumor necrosis factor-α (TNF-α) blockers, anti-interleukins (ILs), and small molecule inhibitors, including Janus kinase (JAK) inhibitors and phosphodiesterase inhibitors in treating DCS.

METHODS: PubMed/Medline, Scopus, and Ovid Embase databases were systematically searched until February 4th, 2024. Study selection was restricted to case reports, case series, cohort studies, and clinical trials published in English-language. NIH and Murad et al.'s quality assessment tools were utilized for critical appraisal.

RESULTS: A total of 34 articles involving 81 patients met the inclusion criteria. The immunomodulators studied for the treatment of DCS include adalimumab, infliximab, certolizumab pegol, ustekinumab, secukinumab, guselkumab, risankizumab, tildrakizumab, apremilast, upadacitinib, and baricitinib. Our findings implied that TNF-α blockers and IL inhibitors were associated with clinical improvement in most individuals with moderate-to-severe DCS, especially in those who had failed earlier treatments. Moreover, certolizumab pegol could be a safe option for DCS in pregnancy. In addition, the prescription of small molecule inhibitors, including JAK inhibitors and apremilast in DCS patients, demonstrated a significant amelioration in DCS symptoms with a desirable safety profile. Nevertheless, the available data was limited, warranting further investigation. Besides, all aforementioned immunomodulators are still debated for their effectiveness on hair regrowth and reversing the scarring process.

CONCLUSIONS: The application of immunomodulators in treating DCS was associated with satisfactory outcomes, although there is still a need to assess the long-term safety and effectiveness of these therapeutic agents in preventing disease progression and new flare-ups.}, } @article {pmid40378149, year = {2025}, author = {Liu, S and Li, J and Xie, G}, title = {Gender differences in the association between weight-adjusted waist index and migraine: A cross-sectional study.}, journal = {PloS one}, volume = {20}, number = {5}, pages = {e0323087}, pmid = {40378149}, issn = {1932-6203}, mesh = {Humans ; *Migraine Disorders/epidemiology/etiology ; Female ; Male ; Cross-Sectional Studies ; Adult ; Middle Aged ; Body Mass Index ; *Waist Circumference ; Sex Factors ; Nutrition Surveys ; Prevalence ; Risk Factors ; Obesity/complications ; United States/epidemiology ; }, abstract = {OBJECTIVE: This study examines how weight-adjusted waist index (WWI) correlates with the occurrence of migraine in U.S. adults.

BACKGROUND: Being overweight significantly increases the likelihood of experiencing migraines; nonetheless, conventional metrics like waist circumference (WC) and body mass index (BMI) might not completely capture the level of migraine risk tied to obesity. WWI integrates the strengths of WC while minimizing its correlation with BMI, which might make it a more accurate indicator of central obesity-related migraine susceptibility.

METHODS: This study performed a cross-sectional analysis using data from 9,688 participants obtained from the National Health and Nutrition Examination Survey (NHANES), covering the years 1999-2004. Migraine occurrence was evaluated through questionnaires, and participants' WWI was computed. Weighted multivariable logistic regression models were used to examine the association between WWI and migraines. Restricted cubic splines (RCS) were applied to evaluate the dose-response relationship between WWI and migraines. Furthermore, interaction tests and subgroup analyses were executed. The receiver operating characteristic (ROC) curve, paired with DeLong et al.'s test, was employed to compare the predictive power of WWI, BMI, and WC for migraines.

RESULTS: The overall prevalence of migraines was found to be 21.50% (weighted population: 31,888,075 out of 148,278,824). In Model 3, the link between WWI and migraines in women showed no statistical significance (OR = 0.94, 95% CI: 0.82-1.07). In this model, each unit increase in WWI among men was linked to a 22% higher risk of migraines (OR = 1.22, 95% CI: 1.05-1.42). When stratified by quintiles, individuals in the third quintile (Q3) displayed a 69% higher likelihood of experiencing migraines compared to those in the first quintile (Q1) (OR = 1.69, 95% CI: 1.19-2.40), with a significant inflection point observed at 10.95 cm/√kg. Significant interactions were noted among various age groups (p for interaction = 0.018). WWI demonstrated a stronger predictive capability for migraine compared to BMI and WC.

CONCLUSION: A U-shaped positive correlation of WWI with migraines was observerd among adult males in the U.S., while no significant correlation was found in females. Within the context of BMI and WC, WWI exhibited a superior predictive capacity for migraines.}, } @article {pmid40375745, year = {2025}, author = {Benjamin, LR and Stahmer, AC and Lau, A and Brookman-Frazee, L}, title = {Caregiver concerns for autistic children differ between publicly funded educational and mental health settings: Findings from a community implementation-effectiveness trial.}, journal = {Autism : the international journal of research and practice}, volume = {}, number = {}, pages = {13623613251337536}, pmid = {40375745}, issn = {1461-7005}, support = {R01 MH111950/MH/NIMH NIH HHS/United States ; R01 MH111981/MH/NIMH NIH HHS/United States ; }, abstract = {This study sought to characterize caregiver concerns for autistic children receiving care in two public service systems-schools and mental health programs-and to identify child and family characteristics associated with these concerns. Caregivers of 353 school-age autistic children in mental health services (n = 192) or schools (n = 161) named, in their own words, the top three concerns for their child. A modified version of Weisz et al.'s Top Problem coding system was developed to expand beyond the original codes, capturing child emotional and behavioral problems, autism features, and adaptive behaviors. Most caregivers (61.8%) identified externalizing behaviors like aggression, as well as social differences (36.3%) and attention difficulties (35.4%) as top problems. Caregivers also mentioned autism-specific concerns related to social responsiveness (54.7%). Participant characteristics, including child age and caregiver race/ethnicity, were associated with concerns. Controlling for child age and caregiver ethnicity, concerns differed by setting; caregivers in mental health (vs. school) settings named more externalizing behaviors, while those in school settings named more restricted repetitive behaviors and social differences. Findings highlight the need to implement setting-specific interventions individualized to caregivers' priorities and to ensure opportunities for cross-system coordination.Lay abstractThis study explored what concerns caregivers have about their autistic children when receiving care from either mental health programs or schools. Caregivers shared, in their own words, the top three concerns they worry about most for their child. Caregivers had many different concerns, including worries about their child's emotions and behaviors, autism-related traits, daily living skills, and ability to manage feelings and behavior. The study also found that caregivers' concerns were linked to family characteristics like their child's age, the caregiver's race or ethnicity, and how many children live in the home. Caregivers' concerns also differed based on where they were getting help. Caregivers in mental health programs were more likely to worry about challenging behaviors like aggression. Caregivers in school settings were more likely to be concerned about their child's social skills and repetitive behaviors. These findings help us better understand what caregivers worry about when seeking support for their child. The findings also show why it is important to use the right strategies in each setting to meet the specific needs of caregivers and their children.}, } @article {pmid40371978, year = {2025}, author = {Shafran, R and Egan, SJ}, title = {Widening the Reach: The Broad Impact of Unguided Self-Help for Eating Disorders.}, journal = {The International journal of eating disorders}, volume = {58}, number = {8}, pages = {1432-1435}, pmid = {40371978}, issn = {1098-108X}, mesh = {Humans ; *Feeding and Eating Disorders/therapy/psychology/prevention & control ; *Cognitive Behavioral Therapy/methods ; *Self Care ; Self Concept ; }, abstract = {A systematic review and meta-analysis conducted by Linardon and colleagues on 27 controlled trials using pure self-help for the prevention and treatment of eating disorders, reported small benefits for co-occurring difficulties such as anxiety, depression, distress and self-esteem. The findings were strongest for pre-selected samples considered at risk or who were symptomatic, and are consistent with literature from other areas indicating that focused interventions have a positive impact on comorbid difficulties. The meta-analysis raises questions about the optimal approach to address comorbidity both within and beyond pure self-help. Understanding the wider impact of disorder-specific approaches compared to transdiagnostic approaches is critical to helping clinicians determine what interventions to use and when. It is notable that CBT interventions across disorders often share treatment techniques and methods to optimize the generalization of learning across difficulties, but such common elements are rarely made explicit. The value of session-by-session measurement as an essential tool to guide clinical decision-making in the context of comorbid difficulties is emphasized. Whilst further work is needed, particularly in clinical samples, the message from Linardon et al.'s meta-analysis is straightforward-pure self-help for the prevention and treatment of eating disorders can have a broad impact in improving mental health.}, } @article {pmid40370097, year = {2025}, author = {Zhai, J and Qi, X and Cai, L and Liu, Y and Tang, H and Xie, L and Wang, J}, title = {NNKcat: deep neural network to predict catalytic constants (Kcat) by integrating protein sequence and substrate structure with enhanced data imbalance handling.}, journal = {Briefings in bioinformatics}, volume = {26}, number = {3}, pages = {}, pmid = {40370097}, issn = {1477-4054}, support = {1955260//National Science Foundation/ ; R01 GM149705/GM/NIGMS NIH HHS/United States ; R01 AG057555/AG/NIA NIH HHS/United States ; R01GM149705//National Science Foundation/ ; /NH/NIH HHS/United States ; R01AG057555//National Science Foundation/ ; }, mesh = {*Neural Networks, Computer ; *Proteins/chemistry/metabolism ; Substrate Specificity ; Catalysis ; *Computational Biology/methods ; Amino Acid Sequence ; Algorithms ; }, abstract = {Catalytic constant (Kcat) is to describe the efficiency of catalyzing reactions. The Kcat value of an enzyme-substrate pair indicates the rate an enzyme converts saturated substrates into product during the catalytic process. However, it is challenging to construct robust prediction models for this important property. Most of the existing models, including the one recently published by Nature Catalysis (Li et al.), are suffering from the overfitting issue. In this study, we proposed a novel protocol to construct Kcat prediction models, introducing an intermedia step to separately develop substrate and protein processors. The substrate processor leverages analyzing Simplified Molecular Input Line Entry System (SMILES) strings using a graph neural network model, attentive FP, while the protein processor abstracts protein sequence information utilizing long short-term memory architecture. This protocol not only mitigates the impact of data imbalance in the original dataset but also provides greater flexibility in customizing the general-purpose Kcat prediction model to enhance the prediction accuracy for specific enzyme classes. Our general-purpose Kcat prediction model demonstrates significantly enhanced stability and slightly better accuracy (R2 value of 0.54 versus 0.50) in comparison with Li et al.'s model using the same dataset. Additionally, our modeling protocol enables personalization of fine-tuning the general-purpose Kcat model for specific enzyme categories through focused learning. Using Cytochrome P450 (CYP450) enzymes as a case study, we achieved the best R2 value of 0.64 for the focused model. The high-quality performance and expandability of the model guarantee its broad applications in enzyme engineering and drug research & development.}, } @article {pmid40369838, year = {2025}, author = {Daneshpour, M and Ducommun-Nagy, C}, title = {Introduction to the Special Section on Contextual Therapy.}, journal = {Family process}, volume = {64}, number = {2}, pages = {e70039}, doi = {10.1111/famp.70039}, pmid = {40369838}, issn = {1545-5300}, mesh = {Humans ; *Family Therapy/methods ; *Couples Therapy/methods ; *Intergenerational Relations ; }, abstract = {This special section on Contextual Therapy offers an in-depth exploration of its foundational principles and evolving applications in addressing complex relational dynamics. Contextual Therapy, founded by Ivan Boszormenyi-Nagy, emphasizes relational ethics, trust, and accountability, providing a framework for understanding intergenerational relationships and addressing systemic injustices. This issue begins with Ducommun-Nagy's conceptual paper, which revisits Contextual Therapy's core principles and introduces innovative ideas for modern therapeutic practice. The collection includes articles that apply Contextual Therapy to diverse cultural contexts, such as Daneshpour's exploration of trust and fairness in couples therapy and Glebova et al.'s examination of sociocultural trauma in immigrant families. van der Meiden delves into the concepts of exoneration and forgiveness, offering insights into their therapeutic implications. Further contributions include Gutierrez and Nleko's analysis of systemic healing in families affected by father absence, and Natrajan-Tyagi and Poulsen's culturally sensitive work with Asian Indian families. Empirical studies, like Rived Ocana's investigation of relational ethics and self-differentiation, provide valuable clinical insights. van Bremen and Natrajan-Tyagi critique neoliberal ideology's impact on family dynamics, showcasing Contextual Therapy's role in promoting authentic relationships. Together, these articles reaffirm Contextual Therapy's relevance, offering practical strategies for therapists and underscoring its adaptability to diverse sociocultural challenges. This special section ensures that Contextual Therapy remains a vital, evolving approach in contemporary therapeutic practice.}, } @article {pmid40369790, year = {2025}, author = {Suga, T and Toyofuku, A}, title = {Challenging the 'Central vs. Peripheral' Classification in Burning Mouth Syndrome: A Critical Analysis of Yang et al.'s Studies.}, journal = {Journal of oral rehabilitation}, volume = {52}, number = {7}, pages = {1160-1163}, doi = {10.1111/joor.14031}, pmid = {40369790}, issn = {1365-2842}, support = {//Japan Society for the Promotion of Science/ ; }, mesh = {Humans ; *Burning Mouth Syndrome/classification/physiopathology/diagnosis ; Nerve Block/methods ; Pain Measurement ; }, abstract = {OBJECTIVE: To critically evaluate the classification of Burning Mouth Syndrome (BMS) into 'peripheral' or 'central' subtypes based on short-term pain relief (≥ 1 cm on the Visual Analogue Scale, VAS) following lingual nerve block, and to explore how quantitative sensory testing (QST) might refine BMS diagnosis.

MATERIALS AND METHODS: We reviewed two recent publications by Yang et al. investigating conditioned pain modulation (CPM) and lingual nerve block efficacy in BMS. We examined their reliance on immediate VAS reductions, sample size, QST findings, and adherence to International Classification of Headache Disorders (ICHD-3) criteria.

RESULTS: Yang et al. reported diminished CPM responses, particularly in the wind-up ratio, among patients classified as central BMS, and highlighted short-term pain relief exclusively in the peripheral subtype. However, categorising patients solely by a ≥ 1 cm VAS reduction may oversimplify the multifactorial nature of BMS, especially when QST findings did not consistently distinguish between groups. Additionally, a small sample size (n = 20) could limit generalisability and obscure subtle pathophysiological differences.

CONCLUSION: Although Yang et al. appropriately applied standard diagnostic guidelines, we recommend integrating subjective (e.g., McGill Pain Questionnaire, Pain Catastrophizing Scale) and objective (e.g., QST, CPM) assessments to capture the complex interplay of peripheral and central mechanisms in BMS. These findings underscore the difficulty of reducing BMS to a strict dichotomy and highlight the need for nuanced, multidimensional approaches. Larger, more diverse cohorts and multidimensional evaluations may improve patient stratification and treatment targeting, ultimately enhancing clinical outcomes for individuals with BMS.}, } @article {pmid40368121, year = {2025}, author = {Irfan, B and Wiseman, E and Boyd, JW and Reader, J and Rahman-Filipiak, A}, title = {Toward a person-centered return of research results of dementia risk: A pluralistic, constructive expansion.}, journal = {Journal of Alzheimer's disease : JAD}, volume = {106}, number = {2}, pages = {540-546}, pmid = {40368121}, issn = {1875-8908}, support = {K23 AG070044/AG/NIA NIH HHS/United States ; P30 AG072931/AG/NIA NIH HHS/United States ; R01 AG074887/AG/NIA NIH HHS/United States ; }, mesh = {Humans ; *Dementia/psychology ; Risk Factors ; *Disclosure/ethics ; Return of Individual Research Results ; }, abstract = {Graham et al.'s article offers a thoughtful account of why disclosing modifiable dementia risk factors to cognitively unimpaired research participants may be ethically defensible. In this Ethics Response, we seek to engage constructively with their arguments, affirming value in a person-centered approach, while also expanding on how cultural, communal, and religious contexts can further illuminate the ethics of returning individual research results. Drawing on emerging ethical issues and examples from diverse settings, this response highlights how stigmatization, religious worldviews, family care traditions, and broader socioeconomic factors may influence the perceived meaning and impact of dementia risk communication.}, } @article {pmid40365114, year = {2025}, author = {Christos, N and Mulholland, J and O'Leary, M and White, RC}, title = {The curious transference of sensations in the 'mismatched-palm' rubber hand illusion.}, journal = {i-Perception}, volume = {16}, number = {3}, pages = {20416695251335161}, pmid = {40365114}, issn = {2041-6695}, abstract = {We describe a disconcerting illusion. The participant looks at the palm of a left rubber hand being touched while receiving synchronous touch on the back of their own hidden right hand. Despite postural incongruence, mismatching handedness and touch being at a different location on the viewed and hidden hands, participants experience the illusion of ownership of the rubber hand and the illusion of feeling touch on the rubber hand. The robustness of the rubber hand illusion to seemingly profound incongruencies is explained with reference to Riemer et al.'s four basic principles for successful embodiment.}, } @article {pmid40355723, year = {2025}, author = {Terao, I}, title = {Comment on Itaya et al.'s trial of anesthetic agents.}, journal = {Journal of anesthesia}, volume = {}, number = {}, pages = {}, pmid = {40355723}, issn = {1438-8359}, } @article {pmid40354274, year = {2025}, author = {Young, JF and Wilfley, DE and Tanofsky-Kraff, M and Mufson, L}, title = {Considerations in selecting comparison conditions in psychotherapy trials: Recommendations for future research.}, journal = {Journal of consulting and clinical psychology}, volume = {93}, number = {5}, pages = {390-395}, doi = {10.1037/ccp0000933}, pmid = {40354274}, issn = {1939-2117}, mesh = {Humans ; *Psychotherapy/standards/methods ; *Randomized Controlled Trials as Topic/standards ; *Research Design/standards ; *Feeding and Eating Disorders/therapy ; }, abstract = {OBJECTIVE: In this commentary, we outline conceptual and methodological concerns we have with a recent randomized trial of two group-delivered transdiagnostic eating disorder treatments (Stice et al., 2023), particularly regarding the description, implementation, and labeling of the comparison condition.

METHOD: We discuss the selection of a control condition in comparative psychotherapy trials; the distinction between adaptations and other types of intervention modifications; the need for processes to ensure that an intervention is developmentally and diagnostically appropriate; and the provision of detailed descriptions of interventions in articles and supplementary materials, as well as making manuals publicly available, to ensure that reviewers and readers can understand the interventions delivered and can accurately interpret the results.

RESULTS: We highlight the potential downstream implications of mislabeling an intervention and conclude that the comparison condition in Stice et al.'s (2023) article should be reclassified to avoid misinterpretation.

CONCLUSIONS: There are published frameworks and guidelines available that promote more detail, precision, and transparency about interventions being tested in clinical trials. We believe it is time for journals to implement these guidelines to ensure that reviewers and readers can fully understand what interventions were tested to draw informed conclusions from the study, replicate research findings, and reliably deliver these interventions in clinical practice. (PsycInfo Database Record (c) 2025 APA, all rights reserved).}, } @article {pmid40352492, year = {2025}, author = {Pang, X and Zhao, K and Yang, C and Zhong, Q and Zhang, N and Jiang, C}, title = {Study on the Photoinduced Isomerization Mechanism of Hydrazone Derivatives Molecular Switch.}, journal = {ACS omega}, volume = {10}, number = {17}, pages = {17898-17906}, pmid = {40352492}, issn = {2470-1343}, abstract = {Improving quantum yield is an important characteristic for enhancing the operational efficiency of light-driven molecular motors. Building upon Cigan et al.'s pioneering work on CH3 substitution for H (RSC Adv., 2015, 5, 62449), we have developed a structural modification strategy for hydrazone-based molecular switches through the replacement of a single oxygen atom with two hydrogen atoms, resulting in a remarkable enhancement of the quantum yield. We systematically investigate the photoinduced isomerization mechanism of the hydrazone derivatives molecular switch using the Tully's surface hopping method on the semiempirical OM2/MRCI level. The results show that the calculated quantum yield for the E-to-Z photoisomerization of this molecular rotary motor is approximately (55 ± 3)% (16.01% for original (Pang, X.-J.; Zhao, K.-Y.; He, H.-Y.; Zhang, N.-B.; Jiang, C.-W. Photoinduced isomerization mechanism of isatin N[2]-diphenylhydrazones molecular switch. Acta Phys. Sin. 2024, 73 (17).) with an average lifetime of the excited state of 122 fs. Additionally, we calculate the time-dependent fluorescence emission spectra and observe a redshift in wavelength accompanied by fluorescence emission quenching, which shows a blue shift compared to the original isatin N[2]-diphenylhydrazone spectrum. Furthermore, we propose that this molecular switch may not have a "dark state".}, } @article {pmid40351578, year = {2025}, author = {Boero, P and Trizano-Hermosilla, I and Vinet, EV}, title = {Psychometric models of emerging adulthood: an evaluation in a Chilean university sample.}, journal = {Frontiers in psychology}, volume = {16}, number = {}, pages = {1483934}, pmid = {40351578}, issn = {1664-1078}, abstract = {This study analyzed three models of the Inventory of the Dimensions of Emerging Adulthood (IDEA): the original by Reifman et al., the version based on Arnett's proposals, and the abbreviated version by Crocetti et al. The sample included 1935 students from four Chilean universities (56% women), with an average age of 21.3 years (SD = 2.04). The 31 items of the instrument were descriptively analyzed, followed by analyses to determine the best-fitting factorial model. Confirmatory Factor Analyses and Exploratory Structural Equation Modeling were utilized. Finally, reliability estimates were obtained. The results showed that Crocetti et al.'s model offered the best fit, consistent with theoretical postulations, and acceptable reliability levels, proving to be the best of the evaluated models. This version confirmed five correlated latent dimensions, providing an integrated interpretation of the Emerging Adulthood construct for use in the Chilean population.}, } @article {pmid40346719, year = {2025}, author = {Öktem, H and Jamil, Y and Sever, SN}, title = {Mapping the anterolateral ligament of the knee: a bibliometric analysis.}, journal = {Knee surgery & related research}, volume = {37}, number = {1}, pages = {21}, pmid = {40346719}, issn = {2234-0726}, abstract = {BACKGROUND: This study aims to evaluate research trends, key contributors, and thematic focuses in research of the anterolateral ligament (ALL) of the knee. It seeks to identify future direction for studies related to long-term clinical outcomes regarding ALL's role in rotational stability, especially in the context of anterior cruciate ligament (ACL) injuries.

METHODS: A bibliometric analysis was conducted using the Web of Science (WoS) database, covering publications from 2012 to 2024 with the search term "anterolateral ligament". A total of 942 studies were identified. Descriptive statistics summarized publication trends, authorship, institutional contributions, and citation metrics. VOSviewer software was used to analyze co-authorship network analysis, keyword co-occurrence mapping, and total citation analysis. Yearly publication and citation trends were analyzed using WoS data. Studies addressing the ALL in other body regions were excluded. Additionally, only authors with at least one publication and one citation were considered, and documents with more than 25 authors were excluded. A total citation analysis was conducted, and 24 relevant keywords with more than 5 occurrences were identified using VOSviewer.

RESULTS: Among 942 publications, 707 were original articles. Research output peaked in 2017 (125 articles). Sonnery-Cottet was the leading author (75 publications), while Universidade De São-Paulo emerged as the top institution (57 publications). Key journals included Arthroscopy: Journal of Arthroscopic and Related Surgery (143 articles) and The American Journal of Sports Medicine (131 articles). Keywords such as "anterior cruciate ligament", "reconstruction", and "rotational stability" dominated, reflecting a focus on ACL injury management. The top ten cited studies accrued 3,86 citations, with Claes et al.'s anatomical study leading (621 citations). Of the 942 ALL-related articles in WoS, 381 focused on anatomy (11,278 citations) while 814 addressed reconstruction (17,048 citations). Keyword trends shifted from anatomical to clinical terms, with anatomy declining and stability, injury, and outcomes gaining prominence from 2021 to 2024.

CONCLUSIONS: This bibliometric analysis underscores the growing interest in ALL research, peaking between 2016 and 2017. While foundational studies on ALL anatomy and biomechanics appear saturated, future research should prioritize clinical outcomes in terms of failure rate, reoperation, the long-term efficacy of ACL-ALL reconstruction, and advancements in imaging techniques.}, } @article {pmid40339220, year = {2025}, author = {Takefuji, Y}, title = {Methodological limitations of linear parametric analysis in biological research: A critical review of NEO-Five personality traits and sleep characteristics study.}, journal = {Sleep medicine reviews}, volume = {81}, number = {}, pages = {102094}, doi = {10.1016/j.smrv.2025.102094}, pmid = {40339220}, issn = {1532-2955}, mesh = {Humans ; Linear Models ; *Personality/physiology ; *Sleep/physiology ; }, abstract = {This paper critically examines the methodological approach employed in Wang et al.'s systematic review and meta-analysis of NEO-Five Personality Traits and sleep characteristics. We identify significant concerns regarding the use of linear parametric methods (Pearson's correlation and meta-regression) in analyzing potentially nonlinear and nonparametric biological data. The paper demonstrates how these analytical tools can lead to distorted results and erroneous conclusions when applied to complex biological systems. We propose alternative nonlinear nonparametric methods, including Spearman's correlation and Kendall's tau for monotonic relationships, and Mutual Information analysis and Effective Transfer Entropy for nonmonotonic interactions, to better capture the intricate relationships in biological research without restrictive assumptions about linearity or data distribution.}, } @article {pmid40338930, year = {2025}, author = {Yousefzadeh, H and Yurdusen, A and Tüter, A and Aksu, GO and Mouchaham, G and Keskin, S and Serre, C and Erkey, C}, title = {Calcium Alginate Aerogel-MIL160 Nanocomposites for CO2 Removal.}, journal = {Langmuir : the ACS journal of surfaces and colloids}, volume = {41}, number = {19}, pages = {11912-11922}, doi = {10.1021/acs.langmuir.5c00143}, pmid = {40338930}, issn = {1520-5827}, abstract = {Using MOFs in powder form leads to mass transfer limitations and large pressure drops in packed bed adsorbers. Use of MOF/aerogel composites (called MOFACs) in bead form could overcome these challenges without compromising the MOF's adsorption performance, as observed with other shaping methods, such as the use of polymeric binders. In this study, Ca-alginate-aerogel-MIL-160(Al) MOFACs (AlgMIL160) were prepared via sol/gel-assisted direct mixing methods, followed by supercritical drying. The gas sorption, powder X-ray diffraction, FTIR, and scanning electron microscopy characterization results showed that the MOF was successfully incorporated into the aerogel, while the MOF structure was preserved. Adsorption measurements were carried out in both static single-component and dynamic binary gas mixture modes. Obtained isotherms were successfully fitted to the Langmuir model followed by ideal adsorbed solution theory (IAST). The single-component gas adsorption isotherms of CO2 on MOFACs with MIL-160(Al) loadings of 25, 50, and 75 wt % revealed a CO2 uptake of 0.43, 0.70, and 0.98 mmol/g at 150 mbar and 25 °C which were higher than that of pure MOF (1.23 mmol/g) based on the MOF loading in the composites, showing the synergistic effect of aerogel and MOF composites. Incorporation of MIL-160(Al) into the aerogel network which is comprised of 75% MIL-160(Al) and 25% Ca-alginate aerogel enhanced MIL-160(Al)'s CO2/N2 IAST selectivity from 53 to 70 at 25 °C and 1000 mbar. Both experimental and simulated CO2 adsorption isotherms showed good agreement. The dynamic adsorption performance of the MOFACs studied by using a binary mixture of 15% CO2/85% N2 was close to the single-component CO2 adsorption with slightly decreased uptake showing the competitive adsorptions between CO2 and N2 molecules. This novel nanocomposite with remarkable CO2 capture performance can be used in gas adsorbers without causing large pressure drops.}, } @article {pmid40338639, year = {2025}, author = {Barchiesi, MA and Calabrese, A and Costa, R and Di Pillo, F and D'Uffizi, A and Tiburzi, L and Zahid, E}, title = {Continuous glucose monitoring in type 2 diabetes: a systematic review of barriers and opportunities for care improvement.}, journal = {International journal for quality in health care : journal of the International Society for Quality in Health Care}, volume = {37}, number = {3}, pages = {}, pmid = {40338639}, issn = {1464-3677}, mesh = {Humans ; *Diabetes Mellitus, Type 2/blood ; *Blood Glucose Self-Monitoring/methods/instrumentation ; Blood Glucose/analysis ; Quality Improvement ; Telemedicine ; Continuous Glucose Monitoring ; }, abstract = {BACKGROUND: Diabetes mellitus, particularly type 2 diabetes (T2DM), is a chronic disease associated with serious complications, such as heart disease, kidney failure, and blindness. Continuous glucose monitoring (CGM) systems have emerged as a more effective alternative to traditional fingerstick testing, offering patients greater control over their condition. Despite their potential benefits, several barriers to CGM sensor use persist, limiting their widespread adoption among patients with T2DM. This review explores the barriers to CGM sensor use, particularly from the patient's perspective.

METHODS: A systematic literature review is conducted following PRISMA guidelines. The search focuses on studies published between January 2018 and June 2024 and is performed in two primary databases, PubMed and Scopus, selected for their relevance to T2DM research. Studies are included if they explore challenges and barriers to CGM adoption, report patient perspectives, or provide insights into the usability and accessibility of technology. The data are analyzed using deductive content analysis, applying Wilson et al.'s thematic categories as a predefined framework to systematically classify and interpret barriers to CGM adoption. This approach ensures methodological consistency and alignment with existing research on eHealth adoption challenges.

RESULTS: The review identifies several key barriers to CGM sensor use despite the benefits, such as improved glucose control and reduced hypoglycemic events. Major challenges include the high cost of sensors, wearability issues, discomfort from adhesive materials, and concerns about the visibility of the sensors. Additionally, patients report difficulties in interpreting the large volumes of data generated by CGM systems, as well as discomfort or fear related to sensor insertion. Lack of technological support, low health literacy, and insufficient social support are also identified as factors contributing to non-adoption.

CONCLUSIONS: Policymakers and healthcare providers are encouraged to address these barriers by developing patient-centered strategies that support the adoption of CGM sensors. Successfully overcoming these challenges can further support integrating CGM sensors with the Chronic Care Model and Automated Insulin Delivery systems. As an implication, this integration has the potential to enhance glycemic control and improve patient quality of life in the management of T2DM. Furthermore, addressing these barriers may drive advancements in sensor design, improve accessibility, and minimize the environmental impact of CGM sensor use.}, } @article {pmid40337818, year = {2025}, author = {Shaw, L and Masood, M and Neufeld, K and Connelly, DM and Stanley, M and Guitar, NA and Garnett, A and Nikkhou, A}, title = {A conceptual framework for defining work disparities: A case of nurses in long term care.}, journal = {Work (Reading, Mass.)}, volume = {80}, number = {4}, pages = {1927-1937}, doi = {10.1177/10519815241295931}, pmid = {40337818}, issn = {1875-9270}, mesh = {Humans ; *Long-Term Care/methods ; *Nurses/psychology ; Workplace/psychology/standards ; Surveys and Questionnaires ; }, abstract = {BackgroundIncreasing the recruitment and retention of nurses within long-term care (LTC) is a growing challenge faced by the healthcare community. Addressing this problem will require a greater understanding of the day-to-day experiences of nurses, including the disparities and unequal treatment experienced by this group of workers (e.g., pay parity, discrimination, and unfair job demands). However, while there is a need to better understand work disparities faced by nurses, a formalized definition and framework for examining work disparities do not exist within the literature.ObjectiveTo create a conceptual framework to define and analyze work disparities experienced by nurses in LTC.MethodsThis analysis was conducted in adherence to Podsakoff et al.'s four-stage series of recommendations. A partial survey of the literature and operationalizations of work disparities were analyzed to create a core list of attributes of work disparities among nurses in LTC. A definition and framework for classifying work disparities were then posited through a dialogic process and refined by testing on two studies.ResultsA definition of work disparities was posited and four categories of work disparities were identified: job security, work compensation, work opportunities, and workplace treatment. A matrix for classifying the variables of work disparities and comparator groups was refined.ConclusionWith the increasing recognition of unequal treatment of nurses in LTC, this framework can enable further research within this area to support and enhance opportunities for the retention and health of the LTC workforce.}, } @article {pmid40335852, year = {2025}, author = {Chea, MS and Keller, EX and Uvin, P and De Coninck, V}, title = {RE: transurethral resection of the prostate across continents: a meta-analysis evaluating quality of gold standard in the twenty-first century.}, journal = {World journal of urology}, volume = {43}, number = {1}, pages = {281}, pmid = {40335852}, issn = {1433-8726}, mesh = {Humans ; Male ; Meta-Analysis as Topic ; *Prostatic Hyperplasia/surgery ; Systematic Reviews as Topic ; *Transurethral Resection of Prostate/standards ; }, abstract = {Porto et al.'s systematic review and meta-analysis of transurethral resection of the prostate (TURP) outcomes across different regions reveals significant improvements in IPSS, Qmax, and postvoid residual (PVR) volume. However, the study is limited by high heterogeneity in PVR outcomes, with substantial variability in clot evacuation, irritative symptoms, and incontinence, suggesting inconsistencies in patient populations, methodologies, and surgical techniques. The study fails to address key confounders such as prostate size, age at surgery, and the use of antiplatelet or anticoagulant therapy, which could significantly influence TURP's outcomes. Additionally, the analysis overlooks the rise of newer treatment alternatives like endoscopic enucleation of the prostate (EEP), which offers better outcomes for high-risk patients. Despite presenting valuable data, the lack of standardization, the omission of emerging treatment options, and failure to consider clinical guidelines limit the generalizability and applicability of Porto et al.'s conclusions on TURP as the gold standard for benign prostatic obstruction.}, } @article {pmid40334916, year = {2025}, author = {Kaltchenko, M and Radtke, S and Kim, E and Wan, J}, title = {Response to Lai and Wei's "Comment on Kaltchenko et al.'s Dupilumab and neuropsychiatric outcomes in pediatric atopic dermatitis: A real-world cohort analysis.".}, journal = {Journal of the American Academy of Dermatology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jaad.2025.04.054}, pmid = {40334916}, issn = {1097-6787}, } @article {pmid40333921, year = {2025}, author = {Schonck, F and Luyer, M and van der Meer, N and Bouwman, A and Nienhuijs, S}, title = {Implementation of a surgical ward innovation: Telemonitoring controlled by healthdot [SWITCH-trial PROTOCOL].}, journal = {PloS one}, volume = {20}, number = {5}, pages = {e0322472}, pmid = {40333921}, issn = {1932-6203}, mesh = {Humans ; Heart Rate ; *Monitoring, Physiologic/methods/instrumentation ; Respiratory Rate ; Telemedicine ; Vital Signs ; *Wearable Electronic Devices ; Workload ; Observational Studies as Topic ; }, abstract = {BACKGROUND: Monitoring patients' vital signs is important to detect abnormalities that may indicate a disturbed postoperative course. However, manual monitoring or so-called spot checks performed by nursing staff require a significant amount and are time-consuming. Wearable devices have been shown to be at least equally effective in collecting these data and have the possibility for continuous monitoring. This technology could enhance improvements in early warning score systems by continuous measurement or ease onward monitoring after earlier discharge. Furthermore, the implementation of wearables for patient monitoring may also decrease the workload for nursing staff. However, it is still unclear how workload is impacted after the implementation of continuous monitoring by wearables in a surgical ward.

METHODS: The level of workload for nursing staff will be assessed by the Integrated Workload Scale [IWS] in an observational study on the stepwise implementation of continuous monitoring at a surgical ward. In a 6-month period, the vital parameters of 500 oncological surgery patients will be recorded using an accelerometer [Healthdot ® Philips] which measures heart rate and respiration rate, gradually leaving out spot checks by nurses. Proctor et al.'s taxonomy of implementation outcomes is used to guide other outcomes: acceptability, appropriateness, feasibility, adoption, penetration, implementation cost and sustainability. Measurements will be performed by device performances of signal noise ratio and [suspected] adverse events, questionnaires Evidence Based Practice Attitude [EBPAS] and System Usability Scale [SUS] and a focus group information that will be processed and objectified by means of a Braun and Clarke thematic analysis.

DISCUSSION: Implementation is complex, especially within healthcare. While the validity of monitoring devices has been studied, their implementation in daily practice has been explored to a limited extent. This study focuses on implementation, with nurses as the primary research group.

AIM: The aim is to investigate the implementation of continuous monitoring using a wearable device regarding efficiency and workload primarily on nursing perspective.

TRIAL REGISTRATION: ClinicalTrials.gov NCT05956210, Registered on 21 July 2023.}, } @article {pmid40322244, year = {2025}, author = {Pflaeging, J and Mackay, B and Schleef, E}, title = {Sociolinguistic monitoring and L2 speakers of English.}, journal = {Linguistics}, volume = {63}, number = {3}, pages = {607-638}, pmid = {40322244}, issn = {1613-396X}, abstract = {This study contributes to a growing body of research on the social meanings of linguistic variation with particular interest in the cognitive processes governing their emergence. Our research follows in the tradition of Labov et al.'s (2011) work on the sociolinguistic monitor, a cognitive mechanism hypothesized to track quantitative linguistic variation and prompt social evaluations (Labov et al. 2011. Properties of the sociolinguistic monitor. Journal of Sociolinguistics 15(4). 431-463). Previous research shows that L1 English listeners are sensitive to frequency variation, but it is unclear whether this also applies to L2 listeners. This study thus replicates Labov et al.'s (2011) original experiment in a context where English is primarily acquired through L2 instruction. To test the generality of sociolinguistic monitoring, we investigate L2 listeners' sensitivity to quantitative differences in sociolinguistic variation (ing) as well as proficiency-based variation. Since participants were L1 speakers of (Austrian) German, we tested evaluations of varying realizations of /θ/ ([θ]/[s]), /d/ ([d]/[t]), and /w/ ([w]/[v]). Experiments included 135 participants, who rated several versions of newscaster test passages regarding professionalism. Our data shows that both sociolinguistic and proficiency-based variation are monitored and evaluated by L2 listeners, albeit to different extents. This supports the assumption that the focus of the monitoring process is socially meaningful variation that includes L1 sociolinguistic but also L2 proficiency-based features.}, } @article {pmid40318295, year = {2025}, author = {Takefuji, Y}, title = {Beyond SHAP: Reliable feature selection methods for clinical prediction models.}, journal = {Archives of gerontology and geriatrics}, volume = {135}, number = {}, pages = {105873}, doi = {10.1016/j.archger.2025.105873}, pmid = {40318295}, issn = {1872-6976}, mesh = {Humans ; Algorithms ; *Depression/diagnosis ; *Models, Statistical ; }, abstract = {This study critically examines the limitations of model-dependent feature importance methods used in clinical prediction modeling, specifically addressing inconsistencies in Xu et al.'s (2025) depression prediction research. We demonstrate how algorithm selection fundamentally alters featured rankings despite similar prediction accuracies, revealing a methodological gap where accuracy validation exists but feature importance validation does not. We propose a comprehensive alternative framework combining statistical and information-theoretic approaches: (1) monotonic relationship detection using Spearman's correlation and Kendall's tau with p-value assessment, and (2) complex interaction analysis using Mutual Information and Effective Transfer Entropy. This dual methodology enables identification of both straightforward variable associations and complex nonlinear dependencies, providing more robust and reliable insights for clinical prediction models.}, } @article {pmid40316871, year = {2025}, author = {Veit, W and Browning, H and Garcia-Pelegrin, E and Davies, JR and DuBois, JG and Clayton, NS}, title = {Dimensions of corvid consciousness.}, journal = {Animal cognition}, volume = {28}, number = {1}, pages = {35}, pmid = {40316871}, issn = {1435-9456}, mesh = {*Consciousness ; Animals ; Animal Welfare ; *Crows ; }, abstract = {Corvids have long been a target of public fascination and of scientific attention, particularly in the study of animal minds. Using Birch et al.'s (2020) 5-dimensional framework for animal consciousness we ask what it is like to be a corvid and propose a speculative but empirically informed answer. We go on to suggest future directions for research on corvid consciousness and how it can inform ethical treatment and animal welfare legislation.}, } @article {pmid40315798, year = {2025}, author = {Andrade, GM and Malbouisson, LMS and Vezozzo, DP and Andraus, W and Mesquita, PS and D'Albuquerque, LAC and Farias, AQ and Carrilho, FJ}, title = {Can elastography predict early allograft dysfunction or loss after liver transplantation? A prospective study of diagnostic accuracy.}, journal = {Clinics (Sao Paulo, Brazil)}, volume = {80}, number = {}, pages = {100634}, pmid = {40315798}, issn = {1980-5322}, mesh = {Humans ; *Elasticity Imaging Techniques/methods ; *Liver Transplantation/adverse effects ; Prospective Studies ; Male ; Female ; Middle Aged ; Adult ; Predictive Value of Tests ; Sensitivity and Specificity ; *Primary Graft Dysfunction/diagnostic imaging ; *Allografts/diagnostic imaging ; Time Factors ; Reproducibility of Results ; Liver/diagnostic imaging ; }, abstract = {INTRODUCTION: The imbalance between the demand for liver transplants and the shortage of donors can be addressed by expanding the donor pool, including using extended criteria donors. This strategy may reduce waiting time and list mortality but can increase poor graft function rates, affecting short-term outcomes. Tools to predict and diagnose Early Allograft Dysfunction (EAD) are crucial. Elastography for Liver Stiffness Measurement (LSM) may predict EAD and graft loss early post-transplant.

METHODS: In this prospective observational study, the authors assessed the diagnostic accuracy of elastography for predicting EAD or loss in liver transplant recipients admitted to the ICU of Hospital das Clínicas, Universidade de São Paulo, from 2016 to 2018. Patients underwent daily LSM from ICU admission to day 7 post-transplant. EAD was defined by Olthoff et al.'s criteria, and allograft loss was defined by the need for retransplantation or death within 180 days.

RESULTS: EAD developed in 27 patients (44.3 %). The median LSM was 2.12 m/s (IQR 1.87-2.67 m/s) for the EAD group and 1.70 m/s (IQR 1.55-1.90 m/s) for the non-EAD group. For predicting EAD, elastography on day 1 had a c-statistic of 0.83, sensitivity 41 %, specificity 97 %, and accuracy 83 % at a cutoff of 2.39 m/s. For predicting early allograft loss, the c-statistic was 0.93, with a sensitivity 76 %, specificity 100 %, and accuracy 93 % at a cutoff of 2.25 m/s on day 1.

CONCLUSION: Elastography demonstrated robust performance in predicting EAD and early graft loss post-transplant, outperforming traditional prognostic scores. Further multicenter studies are needed to confirm these findings.}, } @article {pmid40315223, year = {2025}, author = {Brehon, K and Hung, P and Miciak, M and Leung, WM and Perreault, K and Gross, DP and Weatherald, J and Ronksley, PE and Stickland, MK and Lam, GY}, title = {Living with cystic fibrosis during the COVID-19 pandemic: An interpretive description of healthcare access from patients with cystic fibrosis and their providers in Alberta, Canada.}, journal = {PloS one}, volume = {20}, number = {5}, pages = {e0322911}, pmid = {40315223}, issn = {1932-6203}, mesh = {Humans ; *Cystic Fibrosis/therapy/epidemiology/psychology ; *COVID-19/epidemiology ; *Health Services Accessibility ; Female ; Male ; Adult ; Alberta/epidemiology ; SARS-CoV-2/isolation & purification ; Health Personnel/psychology ; Pandemics ; Young Adult ; Middle Aged ; }, abstract = {BACKGROUND: The current study aimed to explore patient and provider perspectives of the impact of the pandemic on cystic fibrosis healthcare access and service delivery.

METHODS: We used Interpretive Description, a qualitative approach with the end-goal of informing decisions and actions in clinical practice by generating findings that are clinically meaningful and useful. Levesque et al.'s "Conceptual framework of access to health care" informed the development of our interview guides. Interviews were conducted via telephone or Zoom and confidentially transcribed verbatim. Data generation and analysis occurred concurrently to allow for iterative refinements of the interview guides. Analysis was informed by Braun and Clarke's six phases of reflexive thematic analysis. Strategies to enhance rigour and trustworthiness of the findings were utilized.

RESULTS: We completed 13 interviews: 8 with patients and 5 with providers. Three key themes were generated: (a) Tensions due to infection prevention at micro- meso-, and macro- levels; (b) Modifying aspects of person-focused care can bolster perceived quality of clinical encounters; and (c) Accessibility of appropriate healthcare services could improve efficiency of service delivery. Infection prevention at the individual level was not found to be burdensome. Society's compliance with public health measures, or lack thereof, impacted the level of stigma and anxiety experienced by patients with cystic fibrosis. A changed model of care reliant on patient self-report instead of clinician-led testing and in-person assessment due to the transition to virtual care was associated with mixed perceptions since patients with cystic fibrosis were comfortable making care decisions but many participants (patient and provider) felt challenged by the lack of objective data for decision-making. It was essential for patients with cystic fibrosis to feel known, heard, and seen by their providers in order to feel the care was effective. Finally, critical insights around the need for a balance of in-person and virtual care as well as the need for mental health supports were offered.

CONCLUSIONS: The learnings from this study could be translated into practical strategies for improving cystic fibrosis care during the pandemic and beyond. We recommend: (1) a hybrid approach to care moving forward, (2) each patient having a lead physician with others filling in as necessary when scheduling demands, and (3) a reallocation of resources to fund a mental health practitioner position.}, } @article {pmid40314439, year = {2025}, author = {Austin, GI and Korem, T}, title = {Compositional transformations can reasonably introduce phenotype-associated values into sparse features.}, journal = {mSystems}, volume = {10}, number = {5}, pages = {e0002125}, pmid = {40314439}, issn = {2379-5077}, support = {T15 LM007079/LM/NLM NIH HHS/United States ; T15LM007079//U.S. National Library of Medicine/ ; }, mesh = {Humans ; Phenotype ; *Microbiota ; Female ; Machine Learning ; }, abstract = {UNLABELLED: Gihawi et al. (mBio 14:e01607-23, 2023, https://doi.org/10.1128/mbio.01607-23) argued that the analysis of tumor-associated microbiome data by Poore et al. (Nature 579:567-574, 2020, https://doi.org/10.1038/s41586-020-2095-1) is invalid because features that were originally very sparse (genera with mostly zero read counts) became associated with the phenotype following batch correction. Here, we examine whether such an observation should necessarily indicate issues with processing or machine learning pipelines. We show counterexamples using the centered log ratio (CLR) transformation, which is often used for analysis of compositional microbiome data. The CLR transformation has similarities to voom-SNM, the batch-correction method brought into question by Gihawi et al., and yet is a sample-wise operation that cannot, in itself, "leak" information or invalidate downstream analyses. We show that because the CLR transformation divides each value by the geometric mean of its sample, common imputation strategies for missing or zero values result in transformed features that are associated with the geometric mean. Through analyses of both synthetic and vaginal microbiome data sets, we demonstrate that when the geometric mean is associated with a phenotype, sparse and CLR-transformed features will also become associated with it. We re-analyze features highlighted by Gihawi et al. and demonstrate that the phenomenon of sparse features becoming phenotype-associated can also be observed after a CLR transformation, which serves as a counterexample to the claim that such an observation necessarily means information leakage. While we do not intend to address other concerns regarding tumor microbiome analyses, validate Poore et al.'s results, or evaluate batch-correction pipelines, we conclude that because phenotype-associated features that were initially sparse can be created by a sample-wise transformation that cannot artifactually inflate machine learning performance, their detection is not independently sufficient to demonstrate information leakage in machine learning pipelines. Microbiome data are multivariate, and as such, a value of 0 carries a different meaning for each sample. Many transformations, including CLR and other batch-correction methods, are likewise multivariate, and, as these issues demonstrate, each individual feature should be interpreted with caution.

IMPORTANCE: Gihawi et al. claim that finding that a transformation turned highly sparse (mostly zero) features into features that are associated with a phenotype is sufficient to conclude that there is information leakage and to invalidate an analysis. This claim has critical implications for both the debate regarding The Cancer Genome Atlas (TCGA) cancer microbiome analysis and for interpretation and evaluation of analyses in the microbiome field at large. We show by counterexamples and by reanalysis that such transformations can be valid.}, } @article {pmid40314217, year = {2025}, author = {Ju, T and Zhang, Y and Liu, L and Zhao, X and Li, X and Liu, C and Sun, S and Wu, LA}, title = {The role of gut microbiota-mitochondria crosstalk in neurodegeneration: Underlying mechanisms and potential therapies.}, journal = {Neural regeneration research}, volume = {}, number = {}, pages = {}, doi = {10.4103/NRR.NRR-D-24-01419}, pmid = {40314217}, issn = {1673-5374}, abstract = {Emerging evidence suggests that the gut microbiota is closely associated with the pathological manifestations of multiple neurodegenerative diseases via the gut-brain axis, which refers to the crosstalk between the gut and the central nervous system. More importantly, mitochondria have been considered prominent mediators of the interplay between the gut microbiota and the brain. Intestinal microbes may modulate mitochondrial function in the central nervous system to affect the progression of neurodegenerative diseases. Mitochondria are essential for meeting the host's substantial neuronal metabolic demands, maintaining excitability, and facilitating synaptic transmission. Dysfunctional mitochondria are considered critical hallmarks of various neurodegenerative diseases. Therefore, this review provides novel insights into the intricate roles of gut microbiota-mitochondrial crosstalk in the underlying mechanisms during the progression of neurodegeneration, as well as the existing potential therapeutic strategies for neurodegenerative disorders. These suggest intestinal microbiota-mitochondrial interaction play a crucial role in the occurrence and development of neurodegenerative diseases, and targeting this interaction may be a promising therapeutic approach to neurodegenerative diseases. However, this review found that there was relatively little research on the effect of this crosstalk on other neurodegenerative diseases, such as Huntington's disease and Multiple sclerosis, and the potential therapeutic strategies were translated into clinical trials, which face many challenges in developing personalized treatment plans based on the unique gut microbiota of different individuals.}, } @article {pmid40313114, year = {2026}, author = {Zhou, M and Zheng, M and Liang, S and Li, M and Ma, J and Zhang, S and Song, X and Hu, Y and Lyu, Y and Ou, X and Yue, C}, title = {Inherent potential of mitochondria-targeted interventions for chronic neurodegenerative diseases.}, journal = {Neural regeneration research}, volume = {21}, number = {4}, pages = {1409-1427}, doi = {10.4103/NRR.NRR-D-24-01507}, pmid = {40313114}, issn = {1673-5374}, abstract = {The cure rate for chronic neurodegenerative diseases remains low, creating an urgent need for improved intervention methods. Recent studies have shown that enhancing mitochondrial function can mitigate the effects of these diseases. This paper comprehensively reviews the relationship between mitochondrial dysfunction and chronic neurodegenerative diseases, aiming to uncover the potential use of targeted mitochondrial interventions as viable therapeutic options. We detail five targeted mitochondrial intervention strategies for chronic neurodegenerative diseases that act by promoting mitophagy, inhibiting mitochondrial fission, enhancing mitochondrial biogenesis, applying mitochondria-targeting antioxidants, and transplanting mitochondria. Each method has unique advantages and potential limitations, making them suitable for various therapeutic situations. Therapies that promote mitophagy or inhibit mitochondrial fission could be particularly effective in slowing disease progression, especially in the early stages. In contrast, those that enhance mitochondrial biogenesis and apply mitochondria-targeting antioxidants may offer great benefits during the middle stages of the disease by improving cellular antioxidant capacity and energy metabolism. Mitochondrial transplantation, while still experimental, holds great promise for restoring the function of damaged cells. Future research should focus on exploring the mechanisms and effects of these intervention strategies, particularly regarding their safety and efficacy in clinical settings. Additionally, the development of innovative mitochondria-targeting approaches, such as gene editing and nanotechnology, may provide new solutions for treating chronic neurodegenerative diseases. Implementing combined therapeutic strategies that integrate multiple intervention methods could also enhance treatment outcomes.}, } @article {pmid40313084, year = {2026}, author = {Zhang, T and Yin, Y and Xia, X and Que, X and Liu, X and Zhao, G and Chen, J and Chen, Q and Xu, Z and Tang, Y and Qin, Q}, title = {Regulation of synaptic function and lipid metabolism.}, journal = {Neural regeneration research}, volume = {21}, number = {3}, pages = {1037-1057}, pmid = {40313084}, issn = {1673-5374}, abstract = {Synapses are key structures involved in transmitting information in the nervous system, and their functions rely on the regulation of various lipids. Lipids play important roles in synapse formation, neurotransmitter release, and signal transmission, and dysregulation of lipid metabolism is closely associated with various neurodegenerative diseases. The complex roles of lipids in synaptic function and neurological diseases have recently garnered increasing attention, but their specific mechanisms remain to be fully understood. This review aims to explore how lipids regulate synaptic activity in the central nervous system, focusing on their roles in synapse formation, neurotransmitter release, and signal transmission. Additionally, it discusses the mechanisms by which glial cells modulate synaptic function through lipid regulation. This review shows that within the central nervous system, lipids are essential components of the cell membrane bilayer, playing critical roles in synaptic structure and function. They regulate presynaptic vesicular trafficking, postsynaptic signaling pathways, and glial-neuronal interactions. Cholesterol maintains membrane fluidity and promotes the formation of lipid rafts. Glycerophospholipids contribute to the structural integrity of synaptic membranes and are involved in the release of synaptic vesicles. Sphingolipids interact with synaptic receptors through various mechanisms to regulate their activity and are also involved in cellular processes such as inflammation and apoptosis. Fatty acids are vital for energy metabolism and the synthesis of signaling molecules. Abnormalities in lipid metabolism may lead to impairments in synaptic function, affecting information transmission between neurons and the overall health of the nervous system. Therapeutic strategies targeting lipid metabolism, particularly through cholesterol modulation, show promise for treating these conditions. In neurodegenerative diseases such as Alzheimer's disease, Parkinson disease, and amyotrophic lateral sclerosis, dysregulation of lipid metabolism is closely linked to synaptic dysfunction. Therefore, lipids are not only key molecules in neural regeneration and synaptic repair but may also contribute to neurodegenerative pathology when metabolic dysregulation occurs. Further research is needed to elucidate the specific mechanisms linking lipid metabolism to synaptic dysfunction and to develop targeted lipid therapies for neurological diseases.}, } @article {pmid40309753, year = {2025}, author = {Chen, L and Smith, M and Roe, DR and Miranda-Quintana, RA}, title = {Extended Quality (eQual): Radial Threshold Clustering Based on n-ary Similarity.}, journal = {Journal of chemical information and modeling}, volume = {65}, number = {10}, pages = {5062-5070}, pmid = {40309753}, issn = {1549-960X}, support = {R35 GM150620/GM/NIGMS NIH HHS/United States ; }, mesh = {Cluster Analysis ; *Algorithms ; }, abstract = {We are transforming Radial Threshold Clustering (RTC), an O(N[2]) algorithm, into Extended Quality Clustering (eQual), an O(N) algorithm with several novel features. Daura et al.'s RTC algorithm is a partitioning clustering algorithm that groups similar frames together based on their similarity to the seed configuration. RTC has two main issues: it scales as O(N[2]), making it inefficient for large frame counts, and its clustering results depend on the order of input frames whenever there is a tie in the most populated cluster. To address the first issue, we have increased the speed of the seed selection by using k-means++ to select the seeds of the available frames. To address the second issue and make the results invariant with respect to frame order, the densest and most compact cluster is chosen using the extended similarity indices. The new algorithm is able to cluster in linear time and produce more compact and separate clusters.}, } @article {pmid40309191, year = {2025}, author = {Horsham, Z and Haydock-Symonds, AN and Imada, H and Tai, HC and Lau, WL and Shum, TL and Zeng, Y and Chow, HTK and Feldman, G}, title = {Does learning more about others impact liking them? Replication and extension Registered Report of Norton et al.'s (2007) lure of ambiguity.}, journal = {Royal Society open science}, volume = {12}, number = {4}, pages = {250441}, pmid = {40309191}, issn = {2054-5703}, abstract = {Norton et al., 2007, demonstrated a counterintuitive phenomenon that knowing other people better and/or having more information about them is associated with decreased liking. They summarized it as ambiguity leads to liking, whereas familiarity can breed contempt. In a Registered Report with a US Prolific undergraduate student sample (N = 801), we directly replicated Studies 1a, 1b and 2 and conceptually replicated Studies 3 and 4 from Norton et al., 2007. Extending their research, we also proposed that curiosity provides an alternative path to liking, hypothesizing that curiosity mediates the relationship between knowledge and liking. Overall, we found weak support for the original findings. Consistent with the original article, participants believed they would like someone who they knew more about (original: h = 0.52-0.70; replication: h = 0.55-0.75) and that knowledge positively predicts liking (original: h = 0.21-0.45; replication: h = 0.57-0.76). However, we found no indication of the number of traits known influencing liking (original: r = -0.43 to -0.005; replication: r = -0.05 to 0.06) or perceived similarity to the target (d = 0.00), for a mediating effect of perceived similarity, for a dissimilarity cascade effect, or for changes in liking or perceived similarity as a factor of learning more about the target. In our extensions, we found support for a positive relationship between curiosity and liking (r = 0.62-0.70), but not for knowledge and curiosity (r = -0.06 to 0.05). Overall, our findings suggest that learning more about others may not influence perceptions of liking, similarity or curiosity towards them. Materials, data and code are available on https://osf.io/j6tqr/. This Registered Report has been officially endorsed by Peer Community in Registered Reports: https://doi.org/10.24072/pci.rr.100947.}, } @article {pmid40302068, year = {2025}, author = {Nourmohammadi, M and Rahimi Moghadam, S and Jalalian Moghadam, A and Yari, S}, title = {Assessment of Cancer Rate in Mine Workers Exposed to Crystalline Silica.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {26}, number = {4}, pages = {1173-1179}, pmid = {40302068}, issn = {2476-762X}, mesh = {Humans ; *Occupational Exposure/adverse effects ; *Silicon Dioxide/adverse effects ; *Silicosis/etiology/mortality/epidemiology ; *Lung Neoplasms/mortality/epidemiology/etiology/chemically induced ; *Mining ; Male ; Middle Aged ; Follow-Up Studies ; Prognosis ; *Occupational Diseases/etiology/epidemiology ; Adult ; Risk Factors ; }, abstract = {OBJECTIVE: Exposure to Respirable Crystalline silica is considered a significant occupational hazard that can greatly impact the health of workers in mining industries. Consequently, the objective of this study is to evaluate the potential risks associated with exposure to crystalline silica for workers employed in mine.

METHODS: In this descriptive-analytical study, evaluate the occupational exposure of 65 mine workers across five distinct occupational groups by NIOSH 7500 method. To assess the probability of mortality resulting from silicosis and lung cancer, utilized the Mannetje and Rice model. Moreover, the study also focused on evaluating the carcinogenic and non-carcinogenic risks associated with occupational exposure to silica by using the method recommended by the US EPA.

RESULTS: The results of the study indicate that the crusher section, which had a concentration of 0.53 mg/m3, showed the highest level of silica exposure, while the security section, with a concentration of 0.09 mg/m3, exhibited the lowest concentration of Respirable Crystalline silica exposure. The results showed that 85% of the samples exceeded the established occupational exposure limit. The risk of death from lung cancer, as indicated by Rice et al.'s linear model, was estimated to be between 15-139 deaths per 1000 worker exposed to Respirable Crystalline silica. However, according to the Mannetje model, worker with a cumulative exposure range of 4.33-2.84 have a 26.3% risk of developing lung cancer. This cause to approximately 6.3 deaths/1000 P. The carcinogenic risk of 92.1% and the non-carcinogenic risk of 65.5% of the workers were at an unacceptable level.

CONCLUSION: Considering the elevated levels of average exposure within work groups, as well as the increased risk of mortality associated with silicosis and lung cancer, it is imperative to implement comprehensive management and engineering control for the mine workers.}, } @article {pmid40300556, year = {2025}, author = {Zhou, S and Zhou, P and Yang, T and Si, J and An, W and Jiang, Y}, title = {Glucosamine supplementation contributes to reducing the risk of type 2 diabetes: Evidence from Mendelian randomization combined with a meta-analysis.}, journal = {The Journal of international medical research}, volume = {53}, number = {4}, pages = {3000605251334460}, pmid = {40300556}, issn = {1473-2300}, mesh = {Humans ; *Diabetes Mellitus, Type 2/genetics/prevention & control/epidemiology ; *Glucosamine/administration & dosage/therapeutic use ; Mendelian Randomization Analysis ; *Dietary Supplements ; Genome-Wide Association Study ; Risk Factors ; Polymorphism, Single Nucleotide ; }, abstract = {ObjectiveObservational studies on glucosamine supplementation and type 2 diabetes risk have shown inconsistent results, necessitating the use of Mendelian randomization to clarify the true causal relationship.MethodsThe glucosamine supplementation-related genome-wide association study dataset was obtained from the MRC Integrative Epidemiology Unit consortium, whereas type 2 diabetes-related genome-wide association study datasets were obtained from the FinnGen consortium (discovery) and Xue et al.'s meta-analysis (validation). Two-sample Mendelian randomization analyses were performed separately in the discovery and validation datasets, followed by meta-analysis and multivariable Mendelian randomization analyses to verify the robustness of the results of two-sample Mendelian randomization. The estimation of the causal relationship was conducted through the inverse variance weighted method.ResultsGlucosamine supplementation exhibited a significant protective effect against type 2 diabetes, as identified by two-sample Mendelian randomization analysis in the FinnGen consortium (odds ratio: 0.13, 95% confidence interval: 0.02-0.89) and validated in Xue et al.'s meta-analysis (odds ratio: 0.06, 95%; confidence interval: 0.01-0.29). A combined meta-analysis (odds ratio: 0.08, 95%; confidence interval: 0.02-0.27) of the results of two-sample Mendelian randomization confirmed the robustness of these findings. Additionally, multivariable Mendelian randomization analysis (odds ratio: 0.12, 95%; confidence interval: 0.02-0.94), after adjusting for confounding factors, supported the results of two-sample Mendelian randomization. No evidence of heterogeneity or pleiotropy was observed.ConclusionOverall, our results revealed that genetically predicted glucosamine supplementation was inversely associated with the risk of type 2 diabetes, highlighting the potential importance of glucosamine supplementation in preventing type 2 diabetes.}, } @article {pmid40297569, year = {2025}, author = {Bluhm, H and Wohlschlager, D and Pohl, J and Beucker, S and Bieser, J and Schien, D and Widdicks, K and Friday, A and Blair, GS}, title = {Understanding digitalization's environmental impact: why LCA is essential for informed decision-making.}, journal = {npj climate action}, volume = {4}, number = {1}, pages = {41}, pmid = {40297569}, issn = {2731-9814}, abstract = {This comment critiques Gritsenko et al.'s dismissal of environmental assessments such as Life Cycle Analysis (LCA) in analyzing digitalization's environmental impacts. While acknowledging the need for action amidst uncertainty, we argue that LCA yet provides valuable insights into potential impacts, trade-offs, and areas to focus on in a supply chain. Especially in the rapidly evolving digital landscape, LCA helps manage decision-makers' uncertainty and informs targeted measures for sustainable digital infrastructure deployment and use.}, } @article {pmid40297375, year = {2025}, author = {Cheng, X and Fan, Y and Li, S and Li, X and Jin, S and Zhou, C and Feng, Y}, title = {Research landscape and trends of internet addiction disorder: A comprehensive bibliometric analysis of publications in the past 20 years.}, journal = {Digital health}, volume = {11}, number = {}, pages = {20552076251336940}, pmid = {40297375}, issn = {2055-2076}, abstract = {BACKGROUND: Internet addiction disorder (IAD) has emerged as a significant public health concern in the digital age, with implications for mental health and social wellbeing. Despite growing recognition, IAD remains a relatively nascent field within academic research.

METHODS: We conducted a comprehensive bibliometric analysis to explore the global research landscape and trends of IAD. Our methodology involved analyzing author analysis, journal analysis, keywords, and citations in publications related to IAD from 2004 to 2024.

RESULTS: We identified "internet addiction," "internet gaming disorder," and "adolescent" as the most frequently occurring keywords, highlighting significant research areas within IAD. The analysis revealed that terms like "social media addiction," "problematic smartphone use," and "COVID-19" have gained prominence in recent years, reflecting the evolving nature of digital technology's impact on mental health. Clustering analysis illustrated the interdisciplinary nature of IAD research, integrating insights from psychology, sociology, network science, and psychiatry. Citation analysis identified highly influential papers, such as Kuss and Griffiths' review on social networking addiction and Brand et al.'s I-PACE model for internet-use disorders.

CONCLUSIONS: Our findings highlighted the importance of continuing interdisciplinary research to address the multifaceted challenges of IAD. Future research should focus on the intersections of digital behaviors with mental health, personality traits, and social dynamics to develop comprehensive strategies for prevention and intervention.}, } @article {pmid40296838, year = {2025}, author = {Roskies, M and Bray, D and Gualdi, A and Gordon, NA and Nayak, M and Talei, B}, title = {Response to Letter: Roskies et al.'s "Limited Delamination Modifications to the Extended Deep Plane Rhytidectomy: An Anatomical Basis for Improved Outcomes": Anatomical Concerns and the Use of the Term Preservation in Referring to Procedures.}, journal = {Facial plastic surgery & aesthetic medicine}, volume = {27}, number = {3}, pages = {209-211}, doi = {10.1089/fpsam.2025.0098}, pmid = {40296838}, issn = {2689-3622}, } @article {pmid40296836, year = {2025}, author = {Gentile, R}, title = {Letter: Roskies et al.'s "Limited Delamination Modifications to the Extended Deep Plane Rhytidectomy: An Anatomical Basis for Improved Outcomes": Anatomical Concerns and the Use of the Term Preservation in Referring to Procedures.}, journal = {Facial plastic surgery & aesthetic medicine}, volume = {27}, number = {3}, pages = {206-208}, doi = {10.1089/fpsam.2025.0070}, pmid = {40296836}, issn = {2689-3622}, } @article {pmid40287687, year = {2025}, author = {Seo, M and Ryu, J and Park, J}, title = {Effectiveness of a competency-based coordinator of advance care planning competency enhancement program: a mixed method.}, journal = {BMC palliative care}, volume = {24}, number = {1}, pages = {116}, pmid = {40287687}, issn = {1472-684X}, support = {2018R1C1B5086052//National Research Foundation of Korea/ ; 2018R1C1B5086052//National Research Foundation of Korea/ ; 2018R1C1B5086052//National Research Foundation of Korea/ ; }, mesh = {Humans ; *Advance Care Planning/standards/trends ; Female ; Male ; Adult ; Qualitative Research ; Middle Aged ; *Clinical Competence/standards ; }, abstract = {BACKGROUND: Clinical Ethics Support Services (CESS) improve health-care quality by systematically identifying and resolving ethical issues. CESS providers should be trained to understand patients' difficulties with existential issues and advocate on their behalf. This study evaluates the effectiveness of educational programs to enhance the competencies to solve ethical issues in clinical practice for CESS providers related to life-sustaining-treatment, based on Jonsen et al.'s "the four topics approach."

METHODS: This is an explanatory sequential mixed-method study conducted in quantitative and qualitative phases. Participants included 52 life-sustaining medical workers at general hospitals. The participants were categorized into 24 experimental and 28 control groups, including nurses, social workers, and legal administrations. The program encompassed bioethics, end-of-life care, critical thinking, decision-making training through clinical ethics cases, role-playing, communication skills, and discussions. In the quantitative phase, a quasi-experimental study design with pre-test, intervention, and post-test was used. The program for experimental group was provided through 8 sessions spread across 4 weeks. The participants' experiences were explored through semi-structured interviews in the qualitative phase.

RESULTS: After the education, the experimental and control groups differed significantly in critical thinking disposition, and hospice and palliative care knowledge. Participants acknowledged that critical thinking education improved their ability to analyze and evaluate clinical ethical dilemmas.

DISCUSSION: The case-based, role-playing intervention effectively enhanced participants' communication and critical thinking skills concerning life-sustaining treatments. Participants highlighted the importance of ongoing education and professional development to maintain core knowledge and skills, aiming to enhance the quality of care for patients, families, and colleagues.

TRIAL REGISTRATION: This study was retrospectively registered as a code (No: KCT0009687) in the Korean Clinical Trial Service on August 9, 2024.URL: https://cris.nih.go.kr/cris/search/detailSearch.do?seq=27805&status=5&seq_group=27805&search_page=M .}, } @article {pmid40280282, year = {2025}, author = {Matsuda, KM and Kotani, H and Sato, S and Yoshizaki, A}, title = {Unveiling the hidden syndrome: The enigma of anti-transcobalamin receptor autoantibodies.}, journal = {Immunology letters}, volume = {275}, number = {}, pages = {107028}, doi = {10.1016/j.imlet.2025.107028}, pmid = {40280282}, issn = {1879-0542}, mesh = {Humans ; *Autoantibodies/immunology ; *Autoimmune Diseases/immunology ; Vitamin B 12/therapeutic use ; Animals ; *Vitamin B 12 Deficiency/immunology ; Syndrome ; *Antigens, CD/immunology ; *Receptors, Cell Surface/immunology ; }, abstract = {The transcobalamin receptor (CD320) functions as a critical mediator for vitamin B12 uptake in cells, with emerging evidence linking autoantibodies against CD320 to various autoimmune conditions. Pluvinage et al.'s recent study identified anti-CD320 autoantibodies as a cause of autoimmune vitamin B12 central deficiency, specifically affecting the central nervous system while sparing peripheral nerves. Their findings align with our previous work showing anti-CD320's role in cutaneous arteritis. Both studies identified overlapping CD320 epitopes targeted by autoantibodies and demonstrated the therapeutic efficacy of high-dose vitamin B12 supplementation in mitigating symptoms. Expanding on these findings, we observed anti-CD320 autoantibodies in other inflammatory disorders such as systemic sclerosis, suggesting a broader clinical relevance. The work by Pluvinage et al. and our group supports the concept of an "anti-CD320-associated syndrome," with high-dose B12 supplementation as a promising treatment strategy. Further research is needed to fully elucidate the tissue-specific mechanisms and pathophysiology underlying these autoimmune conditions.}, } @article {pmid40271071, year = {2025}, author = {Luo, H and Wei, S and Fu, S and Han, L}, title = {Role of Achyranthes aspera in neurodegenerative diseases: current evidence and future directions.}, journal = {Frontiers in pharmacology}, volume = {16}, number = {}, pages = {1511011}, pmid = {40271071}, issn = {1663-9812}, abstract = {Neurodegenerative diseases are caused by the progressive degeneration of neurons and/or their myelin sheaths, ultimately leading to cognitive and motor dysfunction. Due to their complex pathogenesis and the limited efficacy of therapeutic drugs, these diseases have attracted significant attention. Achyranthes aspera, belongs to family Amaranthaceae, has been extensively used in the traditional and folk medicines for the treatment of various ailments. Modern research has revealed that Achyranthes aspera possesses various pharmacological effects, including cardiocerebrovascular protection, immune regulation, antioxidation, and anti-aging. Furthermore, the neuroprotective effects of Achyranthes aspera have been confirmed by numerous scientific studies. This review focuses on the primary pharmacological effects and mechanisms of Achyranthes aspera in the prevention and treatment of neurodegenerative diseases, as well as their potential application prospects. This review aims to provide insights into the potential clinical applications and research directions of Achyranthes aspera in neurodegenerative diseases.}, } @article {pmid40261585, year = {2025}, author = {Chen, Z}, title = {Challenges and potential of ccfDNA as a preoperative biomarker for adrenocortical adenomas: insights from Xu et al.'s study.}, journal = {Journal of endocrinological investigation}, volume = {48}, number = {7}, pages = {1689-1690}, pmid = {40261585}, issn = {1720-8386}, } @article {pmid40260721, year = {2025}, author = {Gerber, LM and Shulman, KS and Wright, MS and Schiff, ND and Fins, JJ}, title = {Qualitative Analysis of Symptoms from the Central Thalamic Deep Brain Stimulation Trial for Traumatic Brain Injury.}, journal = {NeuroRehabilitation}, volume = {56}, number = {2}, pages = {143-151}, doi = {10.1177/10538135241296732}, pmid = {40260721}, issn = {1878-6448}, mesh = {Humans ; *Brain Injuries, Traumatic/therapy/complications/psychology ; *Deep Brain Stimulation/methods ; Male ; Female ; Adult ; Middle Aged ; Qualitative Research ; Family/psychology ; *Thalamus ; }, abstract = {BackgroundStudies of moderate-to-severe traumatic brain injury (TBI) report persistent clinical impairment post-injury. In the CENTURY-S study of deep brain stimulation (DBS) in chronic TBI, Schiff et al.'s paper, "Thalamic deep brain stimulation in traumatic brain injury: a phase 1, randomized feasibility study" demonstrated improvements in executive control. A companion narrative analysis by Fins et al., "Subject and Family Perspectives from the Central Thalamic Deep Brain Stimulation Trial for Traumatic Brain Injury" Parts I and II described improvements in cognitive, behavioral, and emotional capabilities.ObjectiveThe present study provides an aggregate symptom assessment utilizing pre- and post-DBS narratives from subjects and their family members.MethodsDrawing upon participants from the CENTURY-S study, Fins et al. conducted semi-structured interviews with five subjects with moderate-to-severe TBI and their family members. Transcripts were subsequently coded deductively and inductively in Dedoose by two independent investigators.ResultsSubjects and families frequently volunteered memory and cognitive symptoms as well as difficulties with self-regulation, frustration, and irritability pre-DBS. Following stimulation, four subjects and four families noted improvement in memory and attention and focus, while three subjects and five families volunteered improvements in self-regulation. Fatigue improved in three subjects who previously reported this symptom and in one who did not.ConclusionsSecondary qualitative analysis of narrative data of DBS trial participants supports the incorporation of qualitative data as additional outcome measures in studies of DBS in TBI.}, } @article {pmid40254355, year = {2025}, author = {Sun, H}, title = {From MC1R to MC5R, a new horizon for the podoprotective effect of melanocortin.}, journal = {Kidney international}, volume = {107}, number = {5}, pages = {779-781}, doi = {10.1016/j.kint.2025.01.026}, pmid = {40254355}, issn = {1523-1755}, support = {R01 DK136563/DK/NIDDK NIH HHS/United States ; }, mesh = {*Receptor, Melanocortin, Type 1/metabolism/agonists ; Humans ; Signal Transduction/drug effects ; *Podocytes/drug effects/metabolism/pathology ; Animals ; *Receptors, Melanocortin/metabolism/agonists ; Glycogen Synthase Kinase 3 beta/metabolism ; *Melanocortins ; }, abstract = {The successful use of adrenocorticotropic hormone in treating proteinuric glomerulopathies attached new importance to the melanocortin receptors. While MC1R was originally identified as the receptor mediating melanocortins' podoprotection, Chen et al.'s work in this issue highlights the role of MC5R in maintaining podocyte integrity in the face of stressors, by modulating glycogen synthase kinase-3 β signaling. These findings fill in a gap about melanocortin signaling in podocytes, supporting the therapeutic potential of MC5R agonism, while prompting questions for discussion.}, } @article {pmid40252666, year = {2025}, author = {Balendra, R and Sreedharan, J and Hallegger, M and Luisier, R and Lashuel, HA and Gregory, JM and Patani, R}, title = {Amyotrophic lateral sclerosis caused by TARDBP mutations: from genetics to TDP-43 proteinopathy.}, journal = {The Lancet. Neurology}, volume = {24}, number = {5}, pages = {456-470}, doi = {10.1016/S1474-4422(25)00109-7}, pmid = {40252666}, issn = {1474-4465}, support = {/WT_/Wellcome Trust/United Kingdom ; CC0103/CRUK_/Cancer Research UK/United Kingdom ; R01 NS127186/NS/NINDS NIH HHS/United States ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/pathology/metabolism ; *DNA-Binding Proteins/genetics/metabolism ; *TDP-43 Proteinopathies/genetics/pathology ; *Mutation/genetics ; }, abstract = {Mutations in the TARDBP gene, which encodes the TDP-43 protein, account for only 3-5% of familial cases of amyotrophic lateral sclerosis and less than 1% of cases that are apparently idiopathic. However, the discovery of neuronal inclusions of TDP-43 as the neuropathological hallmark in the majority of cases of amyotrophic lateral sclerosis has transformed our understanding of the pathomechanisms underlying neurodegeneration. An individual TARDBP mutation can cause phenotypic heterogeneity. Most mutations lie within the C-terminus of the TDP-43 protein. In pathological conditions, TDP-43 is mislocalised from the nucleus to the cytoplasm, where it can be phosphorylated, cleaved, and form insoluble aggregates. This mislocalisation leads to dysfunction of downstream pathways of RNA metabolism, proteostasis, mitochondrial function, oxidative stress, axonal transport, and local translation. Biomarkers for TDP-43 dysfunction and targeted therapies are being developed, justifying cautious optimism for personalised medicine approaches that could rescue the downstream effects of TDP-43 pathology.}, } @article {pmid40249032, year = {2025}, author = {Jangid, C and Dalal, J and Malik, KK}, title = {Estimation of postmortem submersion interval using total aquatic decomposition scores of human cadavers from Punjab.}, journal = {Journal of forensic sciences}, volume = {70}, number = {4}, pages = {1593-1602}, doi = {10.1111/1556-4029.70040}, pmid = {40249032}, issn = {1556-4029}, mesh = {Humans ; *Postmortem Changes ; *Immersion ; Forensic Pathology ; Male ; Female ; India ; Middle Aged ; Adult ; Temperature ; Aged ; *Water ; Reproducibility of Results ; Young Adult ; Regression Analysis ; }, abstract = {Estimation of the postmortem submersion interval (PMSI) using total aquatic decomposition scores (TADS) has shown considerable promise in recent forensic research. Since decomposition is a time- and temperature-dependent process, the Accumulated Degree Day (ADD) of water has been linked with TADS to improve the accuracy of PMSI estimations. Expanding research across diverse geographical areas and aquatic environments (lentic, lotic, freshwater, and saltwater) is essential to enhance the reliability and applicability of scoring methods. This study analyzed 50 cases from different districts of Punjab, with TADS ranging from 4 to 22, calculated using Heaton et al.'s method. These scores corresponded to various decomposition stages, with 22 cases in the early floating stage (ADD: 9.79-104.54), 21 cases in the floating decay stage (ADD: 104.54-459.33), and 7 cases in the advanced floating decay stage (ADD: 617.58-2018.19). Furthermore, a robust correlation between TADS and PMSI (R[2] = 0.925, p < 0.001) confirms the reliability of TADS in estimating PMSI. The established regression equation, PMSI = 10 - 0.160 + 0.07316 × TADS $$ \mathrm{PMSI} \kern0.5em =\kern0.5em {10} ^{\left(-0.160\kern0.5em +\kern0.5em 0.07316\times \mathrm{TADS} \right)} $$ , provides a predictive tool for PMSI estimation. The findings suggest that TADS is a reliable indicator of PMSI and can be effectively applied in subtropical climates. The established regression equations provide a practical tool for estimating PMSI in human remains recovered from regions with similar climatic conditions.}, } @article {pmid40246656, year = {2025}, author = {Wu, S}, title = {Enhancing methodological rigor: Re-evaluating statistical model selection in Tian et al.'s Baduanjin study.}, journal = {Complementary therapies in medicine}, volume = {91}, number = {}, pages = {103166}, doi = {10.1016/j.ctim.2025.103166}, pmid = {40246656}, issn = {1873-6963}, } @article {pmid40238835, year = {2025}, author = {Schafheutle, EI and Moss, AA and Hindi, AMK and Gibson, J and Lovatt, E and Robinson, K and Jacobs, S}, title = {Do pay-for-performance schemes improve quality in community pharmacy? A mixed-methods study exploring stakeholder perspectives on implementation of the nationwide Pharmacy Quality Scheme (PQS) in England?.}, journal = {PloS one}, volume = {20}, number = {4}, pages = {e0319215}, pmid = {40238835}, issn = {1932-6203}, mesh = {England ; Humans ; *Reimbursement, Incentive ; *Community Pharmacy Services/economics/standards ; *Pharmacies/economics/standards ; Pharmacists ; Stakeholder Participation ; *Quality Improvement ; }, abstract = {MAIN STUDY OBJECTIVES: To evaluate implementation and impact (at pharmacy and system level) of the pharmacy quality scheme (PQS), a pay-for-performance quality incentive scheme in community pharmacies in England since 2017.

METHODS: Mixed-methods evaluation. Three linked datasets for 2021/22 (n = 10,135) were analysed for impact of pharmacy size, type (independent, chain, supermarket), location, prescription volume, and region on PQS participation, domains completion and payments. Forty-one qualitative interviews conducted with pharmacists, employers and representative bodies explored views and experiences of PQS implementation and impact. Harrington et al.'s conceptual framework for evaluating community pharmacy pay-for-performance programmes guided qualitative data analysis.

RESULTS: Nearly all community pharmacies in England participated in PQS, with differences identified between chains (99% participation) and independents (16.5%), with income via PQS being an important motivator. Interviewees agreed with policy-makers about the purpose of the PQS being patient safety, patient experience, and clinical effectiveness. Beyond these core dimensions, consistency of service provision, sustainability, and wider system integration were considered important. While PQS was largely viewed as positively impacting pharmacy teams, clinical practice, and patient care, interviewees felt that increasing workloads across the sector made it challenging to focus on quality. They felt that there was a lack of feedback, that impacts were not always visible, and indeed frontline pharmacists were often not aware of published evidence of PQS impacts. Multiple sources of guidance lead to duplication and confusion. Particularly independent pharmacies found PQS workload burdensome and complex.

CONCLUSION: The primary incentive for PQS engagement revolved around income stability for employers, with some positive impact achieved, but obstacles concerning resource implications and sustainability persist. Considering concerns about the viability of community pharmacy and the importance of increasing the scope of pharmaceutical services, these implementation challenges should lead policy-makers to question how best to incentivise quality.}, } @article {pmid40238437, year = {2025}, author = {Jimenez, C and Hoepner, LA}, title = {Exploring Methods to Evaluate HPAI Transmission Risk in Iowa During Peak HPAI Incidence, February 2022-December 2023.}, journal = {International journal of environmental research and public health}, volume = {22}, number = {3}, pages = {}, pmid = {40238437}, issn = {1660-4601}, mesh = {Animals ; Iowa/epidemiology ; *Influenza in Birds/epidemiology/transmission/virology ; *Influenza A Virus, H5N1 Subtype/physiology ; *Geese/virology ; Incidence ; Risk Factors ; Poultry ; Risk Assessment ; *Poultry Diseases/epidemiology/virology/transmission ; }, abstract = {Highly pathogenic avian influenza (HPAI), H5N1 strain, began to circulate in the United States on 8 February 2022. The state of Iowa lost the most domestic poultry to HPAI from February 2022-December 2023. This study conducted preliminary evaluations on two environmental risk factors, (inland water surface area, Canada geese abundance) and the availability of the data needed to evaluate them. Higher Canada geese abundance was significantly associated (X[2] = 4.29, p = 0.04) with HPAI negative counties. Farm location data were unavailable, limiting our analysis. Van den Broeck et al.'s framework was used to evaluate the available data. Outcome data from Animal and Plant Health Inspection Service (APHIS) had the highest data quality score (11). Canada geese and inland water surface area are predictors worth evaluating, but poultry farm location data are needed for a comprehensive evaluation.}, } @article {pmid40237179, year = {2025}, author = {Bas, LM and Roberts, ID and Hutcherson, CA and Tusche, A}, title = {A neurocomputational account of the link between social perception and social action.}, journal = {eLife}, volume = {12}, number = {}, pages = {}, pmid = {40237179}, issn = {2050-084X}, support = {P50 MH094258/MH/NIMH NIH HHS/United States ; 435-2016-1274//Social Sciences and Humanities Research Council of Canada/ ; Conte Center P50 MH094258/MH/NIMH NIH HHS/United States ; RGPIN-2019-04329//Natural Sciences and Engineering Research Council of Canada/ ; }, mesh = {Humans ; Male ; *Social Perception ; Magnetic Resonance Imaging ; Female ; Adult ; Altruism ; Young Adult ; *Brain/physiology ; *Social Behavior ; Computer Simulation ; }, abstract = {People selectively help others based on perceptions of their merit or need. Here, we develop a neurocomputational account of how these social perceptions translate into social choice. Using a novel fMRI social perception task, we show that both merit and need perceptions recruited the brain's social inference network. A behavioral computational model identified two non-exclusive mechanisms underlying variance in social perceptions: a consistent tendency to perceive others as meritorious/needy (bias) and a propensity to sample and integrate normative evidence distinguishing high from low merit/need in other people (sensitivity). Variance in people's merit (but not need) bias and sensitivity independently predicted distinct aspects of altruism in a social choice task completed months later. An individual's merit bias predicted context-independent variance in people's overall other-regard during altruistic choice, biasing people toward prosocial actions. An individual's merit sensitivity predicted context-sensitive discrimination in generosity toward high and low merit recipients by influencing other- and self-regard during altruistic decision-making. This context-sensitive perception-action link was associated with activation in the right temporoparietal junction. Together, these findings point toward stable, biologically based individual differences in perceptual processes related to abstract social concepts like merit, and suggest that these differences may have important behavioral implications for an individual's tendency toward favoritism or discrimination in social settings.}, } @article {pmid40229643, year = {2025}, author = {Pereira, F and Lehmann-Wellig, B and Verloo, H}, title = {Enhancing beliefs and implementation of evidence-based practice among undergraduate nurses using a multi-component educational programme: a pre-post study.}, journal = {BMC medical education}, volume = {25}, number = {1}, pages = {531}, pmid = {40229643}, issn = {1472-6920}, support = {IB-UAS-Nur&Phy/001/17//School of Health Sciences, HES-SO Valais/ Wallis, Switzerland/ ; IB-UAS-Nur&Phy/001/17//School of Health Sciences, HES-SO Valais/ Wallis, Switzerland/ ; IB-UAS-Nur&Phy/001/17//School of Health Sciences, HES-SO Valais/ Wallis, Switzerland/ ; }, mesh = {Humans ; *Students, Nursing/psychology ; *Education, Nursing, Baccalaureate/methods ; Female ; Male ; Curriculum ; *Evidence-Based Practice/education ; Adult ; *Attitude of Health Personnel ; Young Adult ; Surveys and Questionnaires ; }, abstract = {BACKGROUND: Using evidence-based practice (EBP) is one of the core skills that students should have acquired by the end of their Bachelor of Science in Nursing (BSN). However, little is known about how their beliefs about EBP and their frequency of implementation relate to multi-component educational programmes on this topic. This study aims to investigate the impact of a multi-component educational programme on nursing students' beliefs about EBP and their frequency of implementation at the School of Health Sciences, HES-SO Valais.

METHODS: This quantitative, pre-post-design study compared undergraduate nursing students' beliefs about EBP and their frequency of implementation before and after completing a multi-component educational programme on EBP. The programme included integrative workshops based on the steps of EBP held during their clinical internships throughout their three-year curriculum. The study occurred between September 2017 and June 2020: the start and end of their studies. The programme's impact was measured using Melnyk et al.'s self-reported EBP Beliefs and Implementation Scales. Descriptive, comparative, correlational and regression statistics were computed to evaluate nurses' responses and scores.

RESULTS: Ninety-five eligible first-year undergraduate nursing students were invited to participate in this EBP study and 81 completed the pre- and post-test questionnaires. Mean EBP scores improved significantly versus baseline on both the Beliefs (49.1 vs. 53.3; p < 0.001) and Implementation (1.7 vs. 9.0; p < 0.001) scales. Cronbach alphas for the EBP Beliefs scale were 0.799 pre-test (95% CI: 0.729, 0.858) and 0.869 post-test (95% CI: 0.823, 0.907). Cronbach's alphas for the EBP Implementation scale were 0.804 pre-test (95% CI: 0.736, 0.861) and 0.939 post-test (95% CI: 0.918, 0.957). There were significant correlations between EBP Beliefs and Implementation scores (p < 0.001). Linear regression analysis showed that the programme's theory-based component contributed significantly more than clinical internships to raising EBP Beliefs and Implementation scores.

CONCLUSIONS: The multi-component educational programme on EBP improved undergraduate nursing students' EBP Beliefs and Implementation scores. Future research should investigate means of optimally integrating EBP into undergraduate nursing curricula and explore nursing students' intentions to implement EBP in clinical practice.}, } @article {pmid40228738, year = {2025}, author = {Bonomo, G and Bonomo, R and Iess, G and Alimonti, P and Restelli, F and Falco, J and Mazzapicchi, E and Schiariti, MP and Broggi, M and Acerbi, F and Ferroli, P}, title = {Arterial Hypertension After Macrovascular Decompression of Vertebrobasilar Dolichoectasia: Rethinking the Cause-Effect Relationship.}, journal = {World neurosurgery}, volume = {198}, number = {}, pages = {123974}, doi = {10.1016/j.wneu.2025.123974}, pmid = {40228738}, issn = {1878-8769}, mesh = {Humans ; Male ; Female ; *Vertebrobasilar Insufficiency/surgery/complications ; Middle Aged ; *Hypertension/etiology/epidemiology ; Retrospective Studies ; Aged ; *Postoperative Complications/etiology/epidemiology ; *Microvascular Decompression Surgery/adverse effects ; Adult ; *Decompression, Surgical/adverse effects ; Treatment Outcome ; Hemifacial Spasm/etiology ; }, abstract = {OBJECTIVE: This study evaluates the short-term and long-term efficacy, safety, and blood pressure (BP) outcomes in patients with hyperactive dysfunction syndromes (HDSs) caused by neurovascular conflict (NVC) from vertebrobasilar dolichoectasia (VBDE) treated with macrovascular decompression (MaVD), with a focus on BP changes postsurgery.

METHODS: We retrospectively analyzed 38 patients with HDS due to VBDE who underwent MaVD at Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Istituto Neurologico Carlo Besta, Milan. Patients were grouped based on BP changes: worsened hypertension (HT), de novo HT, stable HT, and no HT. Demographic, clinical, surgical, and BP data were recorded and analyzed.

RESULTS: The majority of patients (65.8%) had hemifacial spasm, and 50% were hypertensive preoperatively. Postoperatively, 65.8% developed HT, with 52% showing worsened preoperative HT and 24% developing new HT. MaVD resolved symptoms in 86.8% of patients, with partial resolution in 13.1%. Left-sided NVC was more common, and preoperative HT was significantly associated with postoperative BP elevation. Complications included facial nerve deficits (13.1%) and hearing impairment (21%).

CONCLUSIONS: MaVD proves highly effective in treating HDS from VBDE, with most patients achieving complete symptom resolution. However, a significant proportion experienced increased BP postoperatively, especially those with preexisting HT. These findings support Jannetta et al.'s theory of neurogenic HT and suggest that cardiovascular risk factors like age, male sex, and obesity may predispose patients to BP increases. Left-sided NVC and glossopharyngeal neuralgia may be protective. The transient nature of BP elevation indicates possible long-term compensation. Further studies are needed to clarify the mechanisms behind BP changes and improve management strategies postsurgery.}, } @article {pmid40223466, year = {2025}, author = {Lo, SW and Ko, A and Lin, J and Tu, YF}, title = {Comments on 'Propensity score matching methodology in Riley et al.'s study on type 2 diabetes and obstructive sleep apnoea'.}, journal = {Diabetes, obesity & metabolism}, volume = {27}, number = {7}, pages = {4031-4033}, doi = {10.1111/dom.16396}, pmid = {40223466}, issn = {1463-1326}, } @article {pmid40223280, year = {2025}, author = {Seyyedmoharrami, I and Shamaeian-Razavi, N and Rashidi, A and Alizadeh-Ghandashi, AR}, title = {The mediating role of job resilience in the relationship between humble leadership and teachers' responsibility.}, journal = {Work (Reading, Mass.)}, volume = {81}, number = {3}, pages = {2898-2906}, doi = {10.1177/10519815251324013}, pmid = {40223280}, issn = {1875-9270}, mesh = {Humans ; *Leadership ; *Resilience, Psychological ; *School Teachers/psychology ; Iran ; Male ; Female ; Adult ; Surveys and Questionnaires ; Middle Aged ; }, abstract = {BackgroundThe leadership style of managers is the most important factor in any organization that can play a decisive role on the mental health of employees.ObjectiveThe aim of this research is to investigate the mediating role of job resilience in the relationship between humble leadership and responsibility in primary school teachers.MethodsThe current research method was descriptive and correlational. The statistical population was all first grade elementary school teachers in the east of Iran. 176 people were selected by cluster sampling using Cochran's formula. The data collection tools were Morgan Lyons Job resilience questionnaire, Owens et al.'s humble leadership scale, and Glenn and Nelson's responsibility questionnaire. Data were analyzed using PLS software and structural equation modeling (SEM).ResultsExamining the path coefficients showed that the direct effect of humble leadership on teachers' responsibility (P ≥ 0.05, β=0.32) and job resilience is positive and significant (P ≥ 0.05, β=0.59). The direct effect of job resilience on responsibility was also positive and significant (P ≥ 0.05, β=0.55). Also, the examination of standardized coefficients showed that the indirect effect of humble leadership on teachers' responsibility through job resilience is positive and significant.ConclusionsThe results showed that the variable of job resilience plays a mediating role in the influence of humble leadership on taking responsibility, and by understanding the impact of humble leader behaviors on the development of employee resilience, the development of resilience training programs can be learned and developed.}, } @article {pmid40222791, year = {2025}, author = {Bhardwaj, I and Singh, S and Ansari, AH and Rai, SP and Singh, D}, title = {Effect of stress on neuronal cell: Morphological to molecular approach.}, journal = {Progress in brain research}, volume = {291}, number = {}, pages = {469-502}, doi = {10.1016/bs.pbr.2025.01.010}, pmid = {40222791}, issn = {1875-7855}, mesh = {Humans ; Animals ; *Neurons/pathology/metabolism/physiology ; *Stress, Psychological/pathology/metabolism ; *Brain/pathology ; }, abstract = {Stress can be characterized as any perceived or actual threat that necessitates compensatory actions to maintain homeostasis. It can alter an organism's behavior over time by permanently altering the composition and functionality of brain circuitry. The amygdala and prefrontal cortex are two interrelated brain regions that have been the focus of initial research on stress and brain structural and functional plasticity, with the hippocampus serving as the entry point for most of this knowledge. Prolonged stress causes significant morphological alterations in important brain regions such as the hippocampus, amygdala, and prefrontal cortex. Memory, learning, and emotional regulation are among the cognitive functions that are adversely affected by these changes, including neuronal shrinkage, dendritic retraction, and synaptic malfunction. Stress perturbs the equilibrium of neurotransmitters, neuronal plasticity, and mitochondrial function at the molecular level. On the other hand, chronic stress negatively impacts physiology and can result in neuropsychiatric diseases. Recent molecular research has linked various epigenetic processes, such as DNA methylation, histone modifications, and noncoding RNAs, to the dysregulation of genes in the impacted brain circuits responsible for the pathophysiology of chronic stress. Numerous disorders, including neurodegenerative diseases (NDDs) including Alzheimer's, amyotrophic lateral sclerosis, Friedreich's ataxia, Huntington's disease, multiple sclerosis, and Parkinson's disease, have been linked to oxidative stress as a possible cause.}, } @article {pmid40221694, year = {2025}, author = {Chepo, M and Martin, S and Déom, N and Khalid, AF and Vindrola-Padros, C}, title = {Mind the gap: examining policy and social media discourse on Long COVID in children and young people in the UK.}, journal = {BMC public health}, volume = {25}, number = {1}, pages = {1373}, pmid = {40221694}, issn = {1471-2458}, support = {MR/W029766/1//MRC-UKRI Better Methods, Better Research/ ; MR/W029766/1//MRC-UKRI Better Methods, Better Research/ ; MR/W029766/1//MRC-UKRI Better Methods, Better Research/ ; MR/W029766/1//MRC-UKRI Better Methods, Better Research/ ; MR/W029766/1//MRC-UKRI Better Methods, Better Research/ ; }, mesh = {Humans ; *Social Media ; *COVID-19/epidemiology ; United Kingdom/epidemiology ; Child ; *Health Policy ; Adolescent ; *Policy Making ; }, abstract = {BACKGROUND: Long COVID in children and young people (CYP) has posed significant challenges for health systems worldwide. Despite its impact on well-being and development, policies addressing the needs of CYP remain underdeveloped. This study examines UK Long COVID policies using ethical frameworks, integrating policy and social media analyses to explore public and professional concerns.

METHODS: A mixed-methods approach was applied. Policy documents were reviewed using Thompson et al.'s pandemic preparedness framework and Campbell and Carnevale's child-inclusive ethical model. Social media discourse (12,650 posts) was analysed using Brandwatch™ to identify key themes around CYP and Long COVID policies. Data was collected and triangulated through the LISTEN method, which integrates policy analysis with social media discourse to ensure a holistic understanding of systemic gaps and public perceptions.

RESULTS: Analysis highlighted gaps in accountability, inclusiveness, and transparency in policy development. Social media data reflected significant public dissatisfaction, primarily critiquing government accountability (90% of posts) and delayed policy responsiveness (29% of posts). Key ethical challenges included limited CYP representation and unequal access to services.

CONCLUSIONS: Recommendations include improving transparency, incorporating CYP perspectives in policymaking, and ensuring equitable access to care. These findings provide a foundation for ethically sound and inclusive policies addressing Long COVID in CYP.}, } @article {pmid40217193, year = {2025}, author = {Pataer, M and Abulizi, A and Jumatai, S and Zhang, X and Zhang, X and Zhao, J}, title = {C-shaped canal configuration in mandibular second molars of a selected Uyghur adults in Xinjiang: prevalence, correlation, and differences of root canal configuration using cone-beam computed tomography.}, journal = {BMC medical imaging}, volume = {25}, number = {1}, pages = {116}, pmid = {40217193}, issn = {1471-2342}, support = {82160189, 82260196//National Natural Science Foundation of China/ ; }, mesh = {Humans ; Female ; Male ; *Cone-Beam Computed Tomography/methods ; Adult ; China ; Retrospective Studies ; *Molar/diagnostic imaging/anatomy & histology ; *Dental Pulp Cavity/diagnostic imaging/anatomy & histology ; Middle Aged ; Mandible/diagnostic imaging ; Prevalence ; Young Adult ; *Tooth Root/diagnostic imaging/anatomy & histology ; Aged ; Adolescent ; }, abstract = {OBJECTIVES: To determine the prevalence of C-shaped root canal system configurations and assess the correlation between C-shaped root canal prevalence and root morphology in mandibular second molars among adults in Xinjiang Uyghur population using cone-beam computed tomography (CBCT).

MATERIALS AND METHODS: CBCT imaging data from patients treated at the First Affiliated Hospital of Xinjiang Medical University (Affiliated Stomatology Hospital) were retrospectively analyzed. The prevalence of C-shaped root canal configurations in mandibular second molars was determined based on Fan et al.'s classification. Axial sections of each tooth were evaluated in the coronal, middle, and apical thirds to identify canal configurations and analyze root morphology. The differences in C-shaped canal prevalence between genders and tooth positions were compared. Statistical analysis was performed using the chi-square test (p < 0.05).

RESULTS: A total of 1748 patients were included, with 510 (29.17%) exhibiting C-shaped root canals. Females exhibited a higher prevalence (31.49%) than males (25.15%). C-shaped canals were more frequently observed on the lingual surface (76.8%) than the buccal surface (22.2%). Bilateral symmetry of C-shaped canals was observed in 64.7% of cases. A significant association was found between C-shaped canals and root morphology (p < 0.001). Among patients with C-shaped canals, 66.9% demonstrated symmetrical configurations. The most common configuration was C3 (present in all axial levels), followed by C1 and C2. Mandibular second molars with three roots or type 3/type 4 morphologies exhibited a high probability of C-shaped canals.

CONCLUSIONS: C-shaped canals were more prevalent in females and lingually positioned in mandibular second molars. Bilateral C-shaped canals were frequently symmetrical and more common than unilateral cases. Mandibular second molars with three-root or type 3/type 4 morphologies may indicate a high likelihood of C-shaped canals. The most common configuration was C3, followed by C1 and C2, all present across all axial levels. Understanding these anatomical variations preoperatively can improve clinical management.}, } @article {pmid40214867, year = {2025}, author = {Chen, PF and Dexter, F}, title = {Estimating sample means and standard deviations from the log-normal distribution using medians and quartiles: evaluating reporting requirements for primary and secondary endpoints of meta-analyses in anesthesiology.}, journal = {Canadian journal of anaesthesia = Journal canadien d'anesthesie}, volume = {72}, number = {4}, pages = {633-643}, pmid = {40214867}, issn = {1496-8975}, mesh = {*Anesthesiology/methods/statistics & numerical data ; Humans ; *Meta-Analysis as Topic ; Sample Size ; Data Interpretation, Statistical ; Research Design ; Likelihood Functions ; Normal Distribution ; Confidence Intervals ; Clinical Trials as Topic ; }, abstract = {PURPOSE: Clinical trials often report medians and quartiles due to skewed data distributions. We sought to evaluate the methods currently used in meta-analyses in anesthesiology to estimate means and standard deviations (SDs) from medians and quartiles.

METHODS: We simulated sample sizes (n = 15, 27, 51) and coefficients of variation (CV = 0.15, 0.3, 0.5), representative scenarios in anesthesiology studies, generating data that have a log-normal distribution with zero log-scale means. We calculated generalized confidence intervals for the ratios of means and ratios of SDs using means and SDs estimated from three quartiles in time scale, using Luo et al.'s and Wan et al.'s methods, McGrath et al.'s quantile estimation and Box-Cox transformation, and Cai et al.'s maximum likelihood estimation method.

RESULTS: The method by Luo et al. and Wan et al. produced 95% confidence intervals for the ratio of means with coverage ranging from 92.4% to 93.6%, and for SDs from 79.2 to 89.6. McGrath et al.'s quantile estimation method yielded coverage for mean ratios between 88.5% and 91.5% and SDs between 78.0 and 82.7. McGrath et al.'s Box-Cox transformation method showed coverage for mean ratios from 86.6% to 94.4% and SDs from 67.1 to 83.1. The maximum likelihood estimation method by Cai et al. for nonnormal distributions showed coverage for mean ratios from 78.9% to 86.4% and SDs from 67.6 to 78.0.

CONCLUSIONS: All evaluated methods of estimating means and standard deviations from quartiles of log-normal distributed data result in confidence interval coverages below the expected 95%. Because these methods are widely used in meta-analyses of anesthesiology data, P values reported as < 0.05 cannot be trusted. Anesthesiology journals and investigators should revise reporting requirements for continuous skewed variables. We advise reporting the quartiles, mean, and SD, or the quartiles and including the raw data for the relevant variables as supplemental content. This holistic approach could improve the reliability of statistical inferences in meta-analyses of anesthesiology research, particularly when skewed distributions are involved.}, } @article {pmid40205567, year = {2025}, author = {Darling, EK and Graybrook, R and Jameel, B and Dion, A and Ku-Carbonell, S and Begun, S and Mattison, CA}, title = {How has the integration of midwives into primary healthcare settings impacted access to care? A qualitative descriptive study from Ontario, Canada.}, journal = {BMC health services research}, volume = {25}, number = {1}, pages = {516}, pmid = {40205567}, issn = {1472-6963}, support = {MRC - 167971//Canadian Institutes for Health Research/ ; MRC - 167971//Canadian Institutes for Health Research/ ; MRC - 167971//Canadian Institutes for Health Research/ ; }, mesh = {Humans ; Ontario ; Qualitative Research ; *Primary Health Care/organization & administration ; *Health Services Accessibility/organization & administration ; *Midwifery/organization & administration ; Interviews as Topic ; Female ; Continuity of Patient Care ; Pregnancy ; }, abstract = {PROBLEM: Most primary health care settings in Canada do not offer midwifery care. Midwifery remains poorly understood in Canada by some members of the public and healthcare providers.

BACKGROUND: Most midwives in Canada work in community-based midwifery-led continuity of care models that are not integrated into interprofessional primary healthcare settings.

AIM: To investigate perceptions of how integrating midwives into primary health care teams impacts access to care.

METHODS: We conducted a qualitative descriptive study of expanded midwifery care models in Ontario, Canada. We completed 28 semi-structured interviews with midwives, other healthcare providers, healthcare administrators and policy makers. Interviews were audio recorded, transcribed, and then coded using open coding followed by axial coding in NVivo. We used Levesque et al.'s (Int J Equity Health 12:18, 2013) conceptualization of access to care to inform the interview questions and organize our findings.

FINDINGS: We identified themes related to each of Levesque et al.'s supply side dimensions of access to care. Integrating midwives increased visibility and trust of the profession (approachability and acceptability), decreased access barriers such as travel time and cost (affordability), increased collaboration between healthcare providers (appropriateness), and ensured more timely and available care (availability and accommodation).

DISCUSSION: Integrating midwives into primary healthcare settings can improve access to care, particularly for groups underserved by midwives. Integrating midwifery-led care within interprofessional teams can also enhance care appropriateness for equity-deserving populations.

CONCLUSION: While stand-alone community-based midwifery care remains effective and efficient, policy makers should consider creating or expanding funding that supports the further integration of midwives into primary healthcare teams.}, } @article {pmid40197733, year = {2025}, author = {Lin, J and Kao, TW}, title = {Comments on Xie et al.'s Study on Artificial Intelligence-Assisted Perfusion Density as Biomarker for Screening Diabetic Nephropathy.}, journal = {Translational vision science & technology}, volume = {14}, number = {4}, pages = {11}, pmid = {40197733}, issn = {2164-2591}, } @article {pmid40193512, year = {2025}, author = {Heidelburg, K and Sipior, C and King, J and Cueto Brito, M and Fredrick, S}, title = {A systematic review of cultural adaptations to social emotional learning interventions for PreK-12th grade Black students.}, journal = {School psychology (Washington, D.C.)}, volume = {40}, number = {2}, pages = {121-132}, doi = {10.1037/spq0000676}, pmid = {40193512}, issn = {2578-4226}, mesh = {Humans ; *Black or African American/psychology ; Adolescent ; Child ; *Social Learning ; *Students/psychology ; *Emotions ; Schools ; }, abstract = {Due to the lack of culturally responsive social-emotional learning (SEL) interventions and the negative implications of discipline disproportionality of Black students in schools, there is a dire need to develop and implement SEL interventions that promote racial equity and align with the specific cultural needs of Black youth. This systematic review explores cultural adaptations used in SEL interventions for Black PreK-12 students and their associated outcomes. A total of 15 studies with 339 Black/African American students ranging from 8 to 15 years old were included. Each study used at least four or more culturally adapted elements outlined in Bernal et al.'s (1995) Ecological Validity Framework, and every study utilized content and method adaptation elements to meet the needs of Black students. Outcomes associated with cultural adaptation SEL interventions for Black students included positive changes in racial/ethnic identity and increases in skill acquisition and performance across various social, emotional, and behavioral domains. Findings from the current review expand the research on evidence-based, culturally responsive SEL interventions for Black students and highlight the positive outcomes associated with cultural adaptations of SEL interventions for Black students. (PsycInfo Database Record (c) 2025 APA, all rights reserved).}, } @article {pmid40193176, year = {2025}, author = {Koevoet, D and Van Zantwijk, L and Naber, M and Mathôt, S and van der Stigchel, S and Strauch, C}, title = {Effort drives saccade selection.}, journal = {eLife}, volume = {13}, number = {}, pages = {}, pmid = {40193176}, issn = {2050-084X}, support = {10.3030/863732/ERC_/European Research Council/International ; }, mesh = {Humans ; *Saccades/physiology ; }, abstract = {What determines where to move the eyes? We recently showed that pupil size, a well-established marker of effort, also reflects the effort associated with making a saccade ('saccade costs'). Here, we demonstrate saccade costs to critically drive saccade selection: when choosing between any two saccade directions, the least costly direction was consistently preferred. Strikingly, this principle even held during search in natural scenes in two additional experiments. When increasing cognitive demand experimentally through an auditory counting task, participants made fewer saccades and especially cut costly directions. This suggests that the eye-movement system and other cognitive operations consume similar resources that are flexibly allocated among each other as cognitive demand changes. Together, we argue that eye-movement behavior is tuned to adaptively minimize saccade-inherent effort.}, } @article {pmid40189634, year = {2025}, author = {Hay, WW}, title = {Recommended nutrition for preterm infants-on track, but more research is needed.}, journal = {Pediatric research}, volume = {}, number = {}, pages = {}, pmid = {40189634}, issn = {1530-0447}, abstract = {In this issue of Pediatric Research, Naseh, et al. document that extremely to very preterm infants fed recommended macronutrient intakes using early parenteral nutrition and early and reasonably rapidly advanced enteral feeding of supplemented maternal and donor milk have relatively common outcomes of brain size and morphology at term gestational age and cognition at 2 years of age. Growth rates, ranges of data, and data for individual infants would have been helpful to better assess the impact of the feeding approaches and macronutrient intakes on growth and development of the study infants, but the success of Naseh, et al.'s feeding approaches and meeting recommended macronutrient intakes is encouraging. IMPACT: Preterm infants who are fed recommended macronutrient intakes using early parenteral nutrition and early enteral feeding of supplemented maternal and donor milk have relatively common brain size and morphology at term gestation and cognition at 2 years. These results expand the literature documenting that following rational feeding guidelines produces more optimal nutritional outcomes of preterm infants. Early enteral feeding helps produce more optimal nutrition for preterm infants. More research is needed to produce more optimal intravenous amino acid and lipid products and more optimal feeding approaches, and assess longer term growth, neurodevelopment, and cogniation.}, } @article {pmid40181642, year = {2025}, author = {Blomster Lyshol, JK and Bastos, RVS and Isager, PM and Blystad, MH}, title = {What is empathy for laypeople? - A replication study of Hall, Schwartz, and Duong (2021).}, journal = {The Journal of social psychology}, volume = {}, number = {}, pages = {1-19}, doi = {10.1080/00224545.2025.2482014}, pmid = {40181642}, issn = {1940-1183}, abstract = {To understand how laypeople define empathy, Hall, Schwartz, and Duong (2021) asked U.S. participants to rate how well items from various empathy measures matched their own definitions. The current paper (N = 549) is a replication of Hall, Schwartz, and Duong (2021, Study 2) using a highly similar study procedure, with a small extension consisting of items from an emotional contagion scale. We conducted a multi-group CFA to test the replicability of Hall et al.'s model, but the factor structure was not replicated. As an extension, we conducted an exploratory graph analysis (EGA), that revealed a similar factor structure, though some items were discarded due to poor fit. Additionally, the ranking of the items (i.e. what the participants saw as closest to their definition of empathy) shows the same pattern as in the original study. We consider this to be a successful partial replication of Hall et al.'s (2021) findings.}, } @article {pmid40178423, year = {2025}, author = {Cheong, WSC and Au, XYJ and Lim, MY and Fu, EW and Li, H and Pua, U and Soon, YQA and Gan, YJ}, title = {The efficacy and safety of radiofrequency ablation in papillary thyroid carcinoma: A systematic review and meta-analysis.}, journal = {Annals of the Academy of Medicine, Singapore}, volume = {54}, number = {3}, pages = {170-177}, doi = {10.47102/annals-acadmedsg.2024241}, pmid = {40178423}, issn = {2972-4066}, mesh = {Humans ; *Radiofrequency Ablation/adverse effects/methods ; *Thyroid Cancer, Papillary/surgery ; *Thyroid Neoplasms/surgery ; Treatment Outcome ; Postoperative Complications/epidemiology/etiology ; }, abstract = {INTRODUCTION: Radiofrequency ablation (RFA) avoids the complications of general anaesthesia, reduces length of hospitalisation and reduces morbidity from surgery. As such, it is a strong alternative treatment for patients with comorbidities who are not surgical candidates. However, to our knowledge, there have only been 1 systematic review and 3 combined systematic review and meta-analyses on this topic to date. This systematic review and meta-analysis seeks to evaluate the efficacy and safety of RFA in the treatment of papillary thyroid carcinoma (PTC) with longer follow-up durations.

METHOD: PubMed, Embase and Cochrane databases were searched for relevant studies published from 1990 to 2021; 13 studies with a total of 1366 patients were included. The Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines and Sandelowski et al.'s approach1 to "negotiated consensual validation" were used to achieve consensus on the final list of articles to be included. All authors then assessed each study using a rating scheme modified from the Oxford Centre for Evidence-Based Medicine.

RESULTS: Pooled volume reduction rates (VRRs) from 1 to 48 months after RFA, complete disappearance rates (CDR) and complications were assessed. Pooled mean VRRs were 96.59 (95% confidence interval [CI] 91.05-102.13, I2=0%) at 12 months2-6 and 99.31 (95% CI 93.74-104.88, I2=not applicable) at 48 months.2,5 Five studies showed an eventual CDR of 100%.2,4,7-9 No life-threatening complications were recorded. The most common complications included pain, transient voice hoarseness, fever and less commonly, first-degree burn.

CONCLUSION: RFA may be an effective and safe alternative to treating PTC. Larger clinical trials with longer follow-up are needed to further evaluate the effectiveness of RFA in treating PTC.}, } @article {pmid40170226, year = {2025}, author = {Kue, J and Tate, JA and Piñeiro, B and Szalacha, LA and Phommasathit, B and Pich, S and Menon, U}, title = {Cultural and Linguistic Adaptation of an Evidence-Based Tailored Navigation Intervention to Increase Cancer Screening Uptake Among Southeast Asian Women.}, journal = {Cancer control : journal of the Moffitt Cancer Center}, volume = {32}, number = {}, pages = {10732748251329867}, pmid = {40170226}, issn = {1526-2359}, mesh = {Humans ; Female ; *Early Detection of Cancer/statistics & numerical data/psychology/methods ; *Uterine Cervical Neoplasms/diagnosis/ethnology/prevention & control ; *Breast Neoplasms/diagnosis/ethnology/prevention & control ; Middle Aged ; Adult ; Asia, Southeastern/ethnology ; Emigrants and Immigrants/psychology ; Focus Groups ; Health Knowledge, Attitudes, Practice ; Patient Navigation ; Southeast Asian People ; }, abstract = {BackgroundSoutheast Asian immigrant women in the U.S. have high rates of breast and cervical cancer, yet they are the least likely of all racial/ethnic groups to get screened. To address this disparity, we adapted the evidence-based Tailored Intervention Messaging System[©] (TIMS[©]), which uses tailored messages and navigation by culturally and linguistically matched community health advisors to overcome barriers to cancer screening.ObjectivesThis study describes the cultural and linguistic adaptation of TIMS[©] to improve breast and cervical cancer screening among Southeast Asian immigrant women in the U.S.MethodsGuided by Stirman et al.'s adaptation framework, we conducted focus groups and in-depth interviews to identify key constructs related to cancer screening (knowledge, perceived barriers, perceived risk, benefits, self-efficacy). Using the TIMS[©] and the thematic content from qualitative data, we modified messages for content and context. Messages were divided into three categories: 1) existing messages identified in thematic analyses, 2) existing messages not identified in thematic analyses, and 3) new messages that emerged from thematic analyses.ResultsContextual and content modifications were made to the TIMS[©] message library. Messages were translated into Lao, Khmer, and Vietnamese. Through an iterative process, the investigator, community health advisors, and cultural community advisory board members reviewed and revised the messages for translation accuracy, relevance, and clarity.ConclusionUsing relatable language and context is critical to engaging women from Southeast Asian communities in improving breast and cervical cancer screening uptake. This adaptation approach can be applied to tailor interventions for other languages, cultures, and underrepresented groups.}, } @article {pmid40165691, year = {2025}, author = {Bunce, B and Apostolopoulou, E and Andres, SM and Choy, AP and Requena-I-Mora, M and Brockington, D}, title = {A social network analysis of an epistemic community studying neoliberal conservation.}, journal = {Conservation biology : the journal of the Society for Conservation Biology}, volume = {39}, number = {2}, pages = {e70001}, pmid = {40165691}, issn = {1523-1739}, support = {//Women for Africa Foundation/ ; //María de Maeztu, Spanish Ministry of Science and Innovation/ ; ERC/ERC_/European Research Council/International ; CONDJUST/ERC_/European Research Council/International ; 101054259/ERC_/European Research Council/International ; }, mesh = {*Conservation of Natural Resources ; *Social Network Analysis ; *Politics ; Cooperative Behavior ; Knowledge ; }, abstract = {Researchers typically operate in epistemic communities: groups that share common approaches to research agendas and sociopolitical action and define areas of debate. Although productive in their own spheres, a lack of understanding among these communities can undermine scientific progress. Thus, analyzing epistemic communities is important for understanding the politics of knowledge production. Social network analysis sheds light on these dynamics by mapping the collaborative networks that shape academic output. We used 255 publications examined in Apostolopoulou et al.'s review of neoliberal conservation literature and 2135 additional publications in a social network analysis. We compiled a coauthorship network for 318 authors and found a dispersed and polycentric network with low connectivity and relatively small clusters of scholars collaborating within tightly knit groups. Although the structure is conducive to innovation and diversity, building new connections among dispersed coauthor groups could enrich knowledge sharing to drive novel approaches. We identified central actors in building collaborations among communities and communicating ideas across the network. We considered actor attributes, such as gender and geographic location, alongside centrality measures. We found that seventy percent of the 20 authors with the highest betweenness centrality were men, and only one male author was affiliated to an institution in the Global South. Our analysis of thematic clusters in the literature highlighted the spatial patchiness and partialness of the literature across different subfields. Scholars should undertake more work on identified themes in currently excluded geographic regions through effective interdisciplinary collaborations and with local communities of research and practice and grassroots movements. There is a need to strengthen the field's intellectual diversity and to have a deeper engagement with issues of class, gender, and race. This would allow neoliberal conservation to reimagine conservation in ways that are not only environmentally sustainable, but also socially just.}, } @article {pmid40164635, year = {2025}, author = {Roithmeier, M and Geck, S and Bühner, M and Wehr, S and Weigel, L and Priller, J and Davis, JM and Leucht, S}, title = {COSMIN review of the PANSS Marder factor solution and other factor models in people with schizophrenia.}, journal = {Schizophrenia (Heidelberg, Germany)}, volume = {11}, number = {1}, pages = {51}, pmid = {40164635}, issn = {2754-6993}, abstract = {The Positive and Negative Syndrome Scale (PANSS) is widely used to assess schizophrenia symptoms. Initially designed with three subscales, Marder et al.´s 5-factor-Model (M5M) first proposed in 1997 has been frequently used in treatment trials, but it has never been systematically reviewed for its measurement properties. We utilized the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) guideline for systematic reviews and meta-analytical procedures to assess the psychometric properties of the M5M-PANSS. COSMIN comprises several steps: literature search, risk-of-bias assessments, assessing the updated criteria for good measurement properties, feasibility aspects and grading the quality of the evidence. We further assessed the goodness of fit of other PANSS factor models. We included 95 publications. The M5M-PANSS showed good construct validity, but "insufficient" structural validity. Evidence of other COSMIN domains is largely lacking. Among the multiple (73) factor solutions examined with confirmatory methods, several other 5-factor solutions had better model fit. According to COSMIN rules the M5M should not be recommended for use. Other five-factor models such as the one proposed by Wallwork et al.[1] warrant further evaluation. Nevertheless, the factor composition of the M5M and these other models was relatively similar, so previously published results should not be disregarded.}, } @article {pmid40164522, year = {2025}, author = {Rabel, K and Zimmermann, L and Nold, J and Kohal, RJ and Spies, BC and Adolfsson, E and Lüchtenborg, J and Altmann, B}, title = {Identification of a surface texture parameter panel characterizing surface micromorphologies of differently processed oral implant surfaces.}, journal = {Dental materials : official publication of the Academy of Dental Materials}, volume = {41}, number = {6}, pages = {631-643}, doi = {10.1016/j.dental.2025.03.013}, pmid = {40164522}, issn = {1879-0097}, mesh = {Surface Properties ; *Dental Implants ; Microscopy, Electron, Scanning ; *Titanium/chemistry ; Materials Testing ; Interferometry ; Ceramics/chemistry ; *Dental Prosthesis Design ; Humans ; Biocompatible Materials/chemistry ; Dental Materials/chemistry ; }, abstract = {OBJECTIVES: Inconsistent characterization of oral implant microtopography makes it difficult to compare and evaluate available data on microtopography and the biological response to topographical characteristics. The aim of this investigation was therefore to identify a surface texture parameter panel that enables a discriminative characterization of differently processed oral implant surfaces.

MATERIALS AND METHODS: Surface micromorphologies of titanium- and ceramic-based biomaterials processed by machining or by machining and subsequent post-processing, including blasting, etching, anodization or porous sintering, were analyzed by scanning electron microscopy and white light interferometry. It was then analyzed which of the parameters Sa, Sq, Sz, Ssk, Sku, Str, Sal, Spd, Spc, Sdq and Sdr best characterized morphological surface features and hence should be reported as minimum parameter panel for implant surface characterization.

RESULTS: SEM demonstrated that each surface processing resulted in a specific and biomaterial-dependent micromorphology. The data revealed that the micromorphology of machined surfaces was best characterized by Sa, Sdr, Str and Ssk, and that for post-processed surfaces Spd and Spc were additionally required. Based on these data, Sa, Sdr, Str, Ssk, Spd and Spc were identified as minimum parameter panel for discriminative description of the investigated implant microtopographies.

SIGNIFICANCE: The present investigation identified Sa, Sdr, Str, Ssk, Spd and Spc as minimum parameter panel for discriminative oral implant surface characterization. The widespread use of such a panel combined with biological data will help to identify cell-relevant implant surface structures, thus enabling the design of oral implants with predefined biological response.}, } @article {pmid40164145, year = {2025}, author = {Furze, C and Newall, J and Nickbakht, M and Dawes, P and Ching, TYC and Sharma, M}, title = {A systematic review of barriers and facilitators for ethnically diverse communities in accessing adult and paediatric hearing services.}, journal = {International journal of audiology}, volume = {}, number = {}, pages = {1-11}, doi = {10.1080/14992027.2025.2477755}, pmid = {40164145}, issn = {1708-8186}, abstract = {OBJECTIVE: To conduct a systematic review of identified barriers and facilitators for ethnically diverse adults and children in accessing hearing health services.

DESIGN: Searches were performed in electronic databases MEDLINE, EMBASE, CINAHL, Pychinfo, LLBA, and Scopus. The Strengthening of Reporting of Observational Studies in Epidemiology and Standards for Reporting Qualitative Research were used to assess quality of articles. Barriers and facilitators for ethnically diverse adults and children to access hearing services were summarised descriptively using Levesque et al.'s conceptual framework of access to healthcare.

STUDY SAMPLE: 25 articles met the inclusion criteria.

RESULTS: Barriers and facilitators were identified for every domain of Levesque's framework for ethnically diverse adults, children, and their families. Personal barriers included health literacy, health beliefs, and stigma. Environmental barriers included language, limited cultural and interpreter training for clinicians, time constraints in appointments, direct and indirect costs. Facilitators included availability of translated and/or simplified information, cultural responsiveness training, outreach programs, and community health workers to engage with ethnically diverse communities.

CONCLUSION: With increasingly multicultural societies globally, there is an increased need to provide culturally responsive care and accessible hearing health services. Understanding current barriers and facilitators to accessibility would facilitate global sustainable development goals around reduced inequality, health, and wellbeing.}, } @article {pmid40160764, year = {2025}, author = {Furui, K and Ohue, M}, title = {Benchmarking HelixFold3-Predicted Holo Structures for Relative Free Energy Perturbation Calculations.}, journal = {ACS omega}, volume = {10}, number = {11}, pages = {11411-11420}, pmid = {40160764}, issn = {2470-1343}, abstract = {Free energy perturbation (FEP) calculations are a powerful tool for predicting binding affinities in drug discovery, but their accuracy heavily depends on accurate protein-ligand complex structures. While AlphaFold2 revolutionized protein structure prediction, its inability to predict holo structures limits its application in structure-based drug design. AlphaFold3 and its reproduction HelixFold3 demonstrated the ability to predict protein complexes with various binding partners, including small molecules. In this study, we evaluated HelixFold3's ability to predict protein-ligand complexes using eight targets from Wang et al.'s FEP benchmark set. Our analysis revealed that HelixFold3 outperformed the existing methods, including AlphaFold2, in predicting binding site conformations. Notably, the prediction of holo structures yielded a higher binding site accuracy compared to apo structures. FEP calculations using both HelixFold3-predicted holo and apo structures achieved accuracy comparable to that of calculations using crystal structures. Furthermore, HelixFold3 successfully predicted complex structures for novel derivatives not present in its training data, and FEP calculations using these predicted structures maintained reliable accuracy. These results suggest that HelixFold3-predicted structures can effectively substitute for crystal structures in early stage drug discovery.}, } @article {pmid40151661, year = {2025}, author = {Tamura, M and Cage, E and Perry, E and Hongo, M and Takahashi, T and Seto, M and Shimizu, E and Oshima, F}, title = {Understanding Camouflaging, Stigma, and Mental Health for Autistic People in Japan.}, journal = {Autism in adulthood : challenges and management}, volume = {7}, number = {1}, pages = {52-65}, pmid = {40151661}, issn = {2573-959X}, abstract = {BACKGROUND: Camouflaging refers to behaviors in which autistic individuals mask their autistic characteristics and "pass" as non-autistic people. It is postulated that camouflaging is a response to stigma, and preliminary evidence supports this hypothesis. However, research on this topic outside of Western countries is limited. This study replicated and extended previous work in the West that examined the relationships between camouflaging, stigma, and mental health of autistic adults, with a Japanese sample.

METHODS: Two-hundred eighty-seven autistic people living in Japan (146 men, 120 women, 14 nonbinary, 5 other gender identities, 2 preferred not to say; mean age = 37.5 years, standard deviation = 9.8 years) completed an online survey on camouflaging, perceived stigma, coping strategies for stigma, mental well-being, generalized anxiety, social anxiety, and depression. We used hierarchical multiple regression analyses to investigate the relationships between camouflaging and stigma and coping strategies for stigma. Mediation analyses were also employed to examine whether camouflaging mediated the relationships between stigma and autistic people's mental health.

RESULTS: Replicating previous work, we found that higher camouflaging was associated with higher perceived stigma. Both coping strategies of hiding/denying and valuing/embracing stigmatized characteristics were positively related to camouflaging. Camouflaging mediated the association of stigma with depression, generalized anxiety, and social anxiety (but not well-being).

CONCLUSIONS: Our findings support the hypothesis that camouflaging is closely related to autism-related stigma and can influence the impact of stigma on mental health. More work around social outreach and addressing autism-related stigma would be beneficial to reduce the negative role of camouflaging.}, } @article {pmid40151179, year = {2025}, author = {Parchem, B and Poquiz, J and Rider, GN}, title = {Policy and Health Justice: A Conceptual Model Relating the Legislative Climate to the Suicide Disparity Among Transgender and Gender Diverse Youth.}, journal = {Transgender health}, volume = {10}, number = {1}, pages = {1-6}, pmid = {40151179}, issn = {2688-4887}, abstract = {The suicide disparity among transgender and gender diverse (TGD) youth in the United States is occurring in a legislative climate with an unprecedented increase in anti-trans bills, yet limited restrictive firearm laws. The Policy and Health Justice: Collective Resilience/Resistance Against Trans (youth) Exclusion and Suicide model, based on Wesp et al.'s Intersectionality Research for Transgender Health Justice framework, proposes a pathway for how anti-trans bills and firearm laws contribute to TGD youth suicide through structures of domination, institutional systems, and socio-structural processes. The framework suggests targets for resilience and resistance to restructure the flow of power within systems to ameliorate the TGD youth suicide disparity.}, } @article {pmid40148980, year = {2025}, author = {Harerimana, A and Mchunu, G and Pillay, JD}, title = {Menstrual hygiene management among girls and women refugees in Africa: a scoping review.}, journal = {Conflict and health}, volume = {19}, number = {1}, pages = {20}, pmid = {40148980}, issn = {1752-1505}, abstract = {BACKGROUND: Menstrual Hygiene Management (MHM) presents a significant public health challenge for refugee women and girls in Africa. Displaced populations often lack access to menstrual products, adequate Water, Sanitation, and Hygiene (WASH) infrastructure, as well as comprehensive menstrual health education.

AIM: This scoping review aimed to understand the state of MHM, identify key challenges, and evaluate existing interventions among refugee women and girls in Africa.

METHODS: Employing Levac et al.'s framework, the review analysed evidence from databases like CINAHL, Emcare, PubMed, Scopus, and Web of Science, focusing on studies published between 2014 and 2024. Sixteen articles met the inclusion criteria, and both numerical summaries and descriptive analyses were conducted.

RESULTS: Refugee women and girls often lack access to both disposable and reusable menstrual products, resorting to unhygienic alternatives such as clothing, leaves, and paper. Inadequate WASH facilities restrict safe and private spaces for menstrual management. Cultural stigma and taboos surrounding menstruation contribute to social exclusion and school absenteeism among girls. The interventions included distributing dignity kits, enhancing WASH infrastructure, and providing menstrual health education; however, they were inconsistently implemented due to resource limitations and cultural obstacles.

CONCLUSION: This study highlights the urgent need for sustainable menstrual health solutions in refugee settings. Without access to necessary products, WASH facilities, and stigma-free education, women and girls risk exclusion, health issues, and interrupted education. Addressing these barriers requires consistent, well-resourced interventions that integrate cultural sensitivity to ensure dignity and long-term impact.}, } @article {pmid40147433, year = {2025}, author = {Katz, M and Hilsenroth, M and Rokah, N and Wolster, O and Ziv-Beiman, S}, title = {The Interaction Between Alliance and Technique Use in the Prediction of Client Change: Replication and Extension of Owen et al. (2013) in a Different Cultural Context.}, journal = {Clinical psychology & psychotherapy}, volume = {32}, number = {2}, pages = {e70057}, doi = {10.1002/cpp.70057}, pmid = {40147433}, issn = {1099-0879}, mesh = {Humans ; Male ; Female ; *Therapeutic Alliance ; Adult ; *Cognitive Behavioral Therapy/methods ; United States ; Israel ; *Mental Disorders/therapy/psychology ; Middle Aged ; *Cross-Cultural Comparison ; Treatment Outcome ; Surveys and Questionnaires ; *Psychotherapy, Psychodynamic/methods ; Reproducibility of Results ; *Professional-Patient Relations ; }, abstract = {Although the relationship between alliance and outcome is well established, the relationship between technique and outcome seems to be more complex. Accordingly, interest has been rising in the interaction between alliance and technique. In this study, using the new Hebrew version of the Comparative Psychotherapy Process Scale (CPPS), we set out to replicate and extend Owen et al.'s findings regarding the interaction between psychodynamic-interpersonal (PI) technique, cognitive-behavioural (CB) technique and the alliance with patient rated change, 10 years later, and in a different cultural context (Israel vs. United States). A sample of 112 clients completed an online survey including three measures to rate their most recent session: the CPPS, the Working Alliance Inventory (WAI-SF-P) and the Client Task Specific Change Measure Revised (CTSC-R). We found a significant positive relationship between both PI and CB technique with patient rated change, as well as a significant positive relationship between PI technique and the working alliance. We also found interactions between both PI and CB technique use with alliance, in predicting patient rated change. A PROCESS moderation analysis was utilized to better understand these interactions. Whereas amplified PI technique use was most effective in low alliance levels; CB technique was most effective in the context of a strong alliance. The findings support the notion that the technique-alliance interaction may be related to whether the technique a therapist is considering amplifying is adherent or non-adherent to their primary model.}, } @article {pmid40146602, year = {2025}, author = {Lee, JC and Schlegelmilch, R}, title = {The role of perception in generalization: Commentary on Zaman, Yu, and Verheyen (2023).}, journal = {Journal of experimental psychology. General}, volume = {154}, number = {4}, pages = {1167-1175}, doi = {10.1037/xge0001658}, pmid = {40146602}, issn = {1939-2222}, mesh = {Humans ; *Generalization, Psychological/physiology ; *Perception/physiology ; Individuality ; }, abstract = {Stimulus generalization, or the transfer of learned responses between stimuli, is a critical ability for adaptation to everyday life. In a typical experiment, generalization is assessed by measuring responses to stimuli varying along a physical dimension. Variations in the gradient of learned responses are usually interpreted as differences in the underlying cognitive process of generalization. A recent study by Zaman, Yu, and Verheyen (2023) seeks to challenge this view, arguing that generalization is best modeled by perceptual factors and that individual differences in perception or ability to identify the stimuli are primary drivers of generalization. In this commentary, we outline issues in the methodology and analysis of Zaman et al.'s study and show that their key result is not robust to the addition of theoretically informed alternative models. We conclude that the evidence is not strong enough to support their conclusions regarding the primacy of perceptual processes in generalization. We propose some ways forward for researchers in this field attempting to understand the psychological mechanisms underlying individual differences in stimulus generalization. (PsycInfo Database Record (c) 2025 APA, all rights reserved).}, } @article {pmid40141471, year = {2025}, author = {Shi, J and Yang, L and Peng, B and Wei, G and Yuan, Y}, title = {Analysis of Typical Inclusion Evolution and Formation Mechanism in the Smelting Process of W350 Non-Oriented Silicon Steel.}, journal = {Materials (Basel, Switzerland)}, volume = {18}, number = {6}, pages = {}, pmid = {40141471}, issn = {1996-1944}, support = {21162480ZD//The Major Program of the Central Iron and Steel Research Institute Research and Development Special Fund/ ; }, abstract = {The production of silicon steel involves complex metallurgical processes, where the kind, composition, size, and quantity of the inclusions generated affect the silicon steel properties. This article is based on the smelting process for W350 non-oriented silicon steel produced by a certain factory. By systematically sampling, at key nodes of the converter-RH refining-tundish smelting process, the change in cleanliness of molten steel in the whole smelting process, the evolution of typical inclusions, and the transformation rules for the precipitated phase were analyzed by means of SEM-EDS, ASPEX, and Thermal-Calc. The results indicate that the total oxygen mass fraction in the steel decreases by more than 95% after deoxidation alloying, and the average oxygen mass fraction in the RH outbound steel is 0.0012%. While the nitrogen mass fraction shows a rising trend as a whole, the average nitrogen mass fraction in the tundish steel reaches approximately 0.0014%. Before RH refining, large Al2O3-CaO-SiO2 and Al2O3-CaO-SiO2-MgO composite inclusions are the main inclusions. MnO and Al2O3-SiO2-MnO inclusions are the main inclusions after RH inlet and RH decarburization. After RH deoxidation with aluminum, the inclusions were almost entirely transformed into Al2O3 inclusions. After RH alloying, with the content of Si and Mn increased, the inclusions transformed into Al2O3-SiO2-MnO inclusions. The number of inclusions from RH desulfurization to the RH outbound stage declined significantly, and composite inclusions containing CaS and precipitates such as AlN and MnS began to appear. The inclusions' main types were Al2O3-MgO-CaS, AlN-MnS, AlN, and Al2O3-MgO. The inclusions inside the tundish were the same, but the numbers were slightly increased due to the secondary oxidation of molten steel. More than 80% of the oxide inclusions in the whole process were between 1 μm and 5 μm in size. The average size and the number of inclusions per unit area reached 5.45 μm and 63.1 per mm[2], respectively, after RH deoxidation, and respectively decreased to 3.71 μm and 1.9 per mm[2] during the RH outbound stage, but both increased slightly in the tundish. Thermodynamic calculation shows that Al2O3-MgO inclusions are formed when w([Mg]) > 0.0033% in molten steel at 1873 K. Under the actual temperature of 1828K and w([Al]s) = 0.6515%, the range of w([Mg]) corresponding to the stable existence of Al2O3-MgO is between 0.0053% and 0.1676%. The liquidus temperature of W350 non-oriented silicon steel is 1489 °C. MnS and AlN inclusions are precipitated successively with the solidification of molten steel, and the precipitation temperatures are 1460.7 °C and 1422.2 °C, respectively. As the temperature decreases, the sequence of inclusion precipitation calculated in liquid was as follows: Al2O3-CaO → 2Al2O3-CaO + MnS → 6Al2O3-CaO → Al2O3 + AlN + MnS + CaS.}, } @article {pmid40140866, year = {2025}, author = {Taheri-Ezbarami, Z and Jafaraghaee, F and Sighlani, AK and Mousavi, SK}, title = {Understanding the educational needs of undergraduate nursing students regarding end-of-life care: a qualitative content analysis.}, journal = {BMC research notes}, volume = {18}, number = {1}, pages = {129}, pmid = {40140866}, issn = {1756-0500}, mesh = {Humans ; *Terminal Care ; *Students, Nursing/psychology ; Qualitative Research ; *Education, Nursing, Baccalaureate ; Female ; Male ; Adult ; Young Adult ; *Needs Assessment ; }, abstract = {BACKGROUND: Although nurses have a fundamental role in end-of-life care, nursing curricula have not paid enough attention to this area. This research aimed to understand the educational needs of undergraduate nursing students regarding end-of-life care.

METHODS: This study was a qualitative content analysis conducted in 2023 in which 16 participants, including faculty members, nurses, head nurses, nursing educational supervisors, nursing service managers, PhD and MSc students, were selected purposefully. Individual in-depth semi-structured interviews were used face-to-face and over the phone to collect information. The data was analyzed using Elo and Kyngas' inductive content analysis approach with the help of MAXQDA 2020 software. Also, Elo et al.'s checklist was used to check the rigor of the data.

RESULTS: After coding the interviews, 773 initial codes were generated, which were reduced to 679 after several revisions. These codes were placed into 46 subcategories, 17 categories, and six themes, including the principles of end-of-life care, physical care, psycho-social care, spiritual care, ethical challenges, and after-death care.

CONCLUSION: This study determined the educational needs of undergraduate nursing students regarding end-of-life care. Therefore, it is suggested that the results of this study be considered when designing related educational programs for nursing students and nurses.}, } @article {pmid40137505, year = {2025}, author = {Calderón-Garcidueñas, L and González-Maciel, A and Reynoso-Robles, R and Cejudo-Ruiz, FR and Silva-Pereyra, HG and Gorzalski, A and Torres-Jardón, R}, title = {Alzheimer's, Parkinson's, Frontotemporal Lobar Degeneration, and Amyotrophic Lateral Sclerosis Start in Pediatric Ages: Ultrafine Particulate Matter and Industrial Nanoparticles Are Key in the Early-Onset Neurodegeneration: Time to Invest in Preventive Medicine.}, journal = {Toxics}, volume = {13}, number = {3}, pages = {}, pmid = {40137505}, issn = {2305-6304}, abstract = {Billions of people are exposed to fine particulate matter (PM2.5) levels above the USEPA's annual standard of 9 μg/m[3]. Common emission sources are anthropogenic, producing complex aerosolized toxins. Ultrafine particulate matter (UFPM) and industrial nanoparticles (NPs) have major detrimental effects on the brain, but the USA does not measure UFPM on a routine basis. This review focuses on the development and progression of common neurodegenerative diseases, as diagnosed through neuropathology, among young residents in Metropolitan Mexico City (MMC). MMC is one of the most polluted megacities in the world, with a population of 22 million residents, many of whom are unaware of the brain effects caused by their polluted atmosphere. Fatal neurodegenerative diseases (such as Alzheimer's and Parkinson's) that begin in childhood in populations living in air polluted environments are preventable. We conclude that UFPM/NPs are capable of disrupting neural homeostasis and give rise to relentless neurodegenerative processes throughout the entire life of the highly exposed population in MMC. The paradigm of reaching old age to have neurodegeneration is no longer supported. Neurodegenerative changes start early in pediatric ages and are irreversible. It is time to invest in preventive medicine.}, } @article {pmid40135943, year = {2025}, author = {Mrayyan, MT}, title = {Effects of Nursing Leaders' Toxic Leadership on Nurses' Workplace Satisfaction, Job Engagement, and Turnover Intention: An Online Cross-Sectional Study.}, journal = {Journal of advanced nursing}, volume = {}, number = {}, pages = {}, doi = {10.1111/jan.16923}, pmid = {40135943}, issn = {1365-2648}, abstract = {AIM: Toxic leadership has become prevalent in nursing; however, the literature provides limited evidence of the different outcomes of toxic leadership behaviours. This research investigated nursing leaders' toxic leadership, nurses' workplace satisfaction, job engagement, and turnover intention in Jordan and whether toxic leadership and sample characteristics predict nurses' workplace satisfaction, job engagement, and turnover intention.

METHODS: To reach a more diverse and larger population of nurses, data were gathered in 2023 using an online survey and a cross-sectional research design with convenience snowball sampling of 384 nurses from different hospitals. Nurses "agreed" on the presence of nursing leaders' toxic leadership.

RESULTS: Nurses "agreed" on the presence of nursing leaders' toxic leadership. Similar to Sexton et al.'s (2006) scoring, it was still low (Mean = 3.08/5, Standard Error (SE) = 0.043), which applied in the same magnitude for low nurses' workplace satisfaction (Mean = 2.45/5, SE = 0.036), low nurses' job engagement (Mean = 3.57/5, SE = 0.040), and low nurses' turnover intention (Mean = 3.25/5, SE = 0.038). The highest and lowest means for the four variables. As a part of the workplace satisfaction tool, nurses were asked two open ended-questions about the best and the worst things about their jobs; they answered that nursing provides humanitarian care for patients (n = 178, 95.33%), while the worst thing was the poor work environments, especially related to salaries and workload were (n = 85, 27.25%). Perceived nursing leaders' toxic leadership only predicted perceived nurses' workplace satisfaction (t = 5.79, p = 0.001, Adjusted R[2] = 0.066); perceived nurses' job engagement (t = 5.52, p = 0.001, Adjusted R[2] = 0.067); and perceived nurses' turnover intention (t = 11.16, p = 0.001, Adjusted R[2] = 0.249).

CONCLUSIONS: The major effect of toxic leadership of nursing leaders was on nurses' intention to leave. Given the high global nurse turnover rates, toxic leadership would result in low job satisfaction, stress and emotional exhaustion, and, in turn, decreased quality of nursing care. Therefore, it is essential to confront toxic leadership immediately. Nursing leaders' toxic leadership, nurses' workplace satisfaction, job engagement, and turnover intention were low in the current study. However, even if it has a low level, it should be diagnosed and eradicated at early stages to avoid its disastrous outcomes; toxic leadership has detrimental consequences.

Low workplace satisfaction and job engagement are dangerous; thus, they warrant immediate managerial interventions, such as establishing training programmes and using effective communication.

IMPACT: This study highlights the urgent need for innovative managerial interventions to overcome low workplace satisfaction and job engagement; they are alarming in such rapidly changing work environments.

REPORTING METHOD: Guidelines were followed using the STROBE reporting method.

None.}, } @article {pmid40133015, year = {2025}, author = {Smith, JW and Mayo, A}, title = {A response to Henderson et al.'s commentary on Smith and Mayo (2024).}, journal = {Nursing outlook}, volume = {73}, number = {3}, pages = {102387}, doi = {10.1016/j.outlook.2025.102387}, pmid = {40133015}, issn = {1528-3968}, } @article {pmid40132732, year = {2025}, author = {He, Y and Zheng, Q and Zhifang, Z and Xiaofeng, N and Shenggen, W and Xue, M and Zheng, C and Liu, Z}, title = {When COVID-19 meets diabetes: A bibliometric analysis.}, journal = {Diabetes research and clinical practice}, volume = {223}, number = {}, pages = {112118}, doi = {10.1016/j.diabres.2025.112118}, pmid = {40132732}, issn = {1872-8227}, mesh = {*COVID-19/epidemiology/complications ; Humans ; *Bibliometrics ; *Diabetes Mellitus/epidemiology ; SARS-CoV-2 ; }, abstract = {Coronavirus disease 2019 (COVID-19) survivors are concerned about the likelihood of developing further diseases. This study examines the global trends in scientific research on diabetes associated with COVID-19 from several perspectives. Bibliometric analyses are used to undertake a scientific review of the literature. The Web of Science Core Collection (WoSCC) database was used to acquire bibliographic information on diabetes related to COVID-19 from Jan 2020 to Dec. 2023. The visual map was built via advanced CiteSpace 6.2.R6. 7,348 papers were found. Khunti Kamlesh and Rizzo-Manfredi are the most well-known high-yield authors in this area, and the top ten authors collaborate extensively. Most of these papers came from universities. Harvard Medical School has the most publications, followed by Wuhan University and Huazhong University of Science and Technology. China and the United States are the countries with the most publications. Angiotensin-converting enzymes, chronic disease, intensive care unit, viral infection, and gestational diabetes mellitus were scored 0-11, 2, 3, and 4, respectively. Zhou et al.'s work on this topic, which appeared in the prominent medical journal The Lancet, was cited 1,366 times, highlighting its importance. "clinical characteristics," "diabetes mellitus," "metabolic syndrome," and "angiotensin-converting enzyme" were used as keywords for reference co-citation and clustering data identify. Over the last four years, related investigations have focused primarily on observing clinical aspects. This report is important for developing treatment strategies, directing future research, and guiding clinical practice.}, } @article {pmid40129698, year = {2025}, author = {Wu, J and Liao, S and Li, Y and Xu, F and Zhao, H and Li, C and Liu, Y and Zhi, X and Lin, H and Tu, Z and Shu, L and Li, J and Li, Y and Canavese, F and Xu, H and Liu, Y}, title = {Radiographic features of Wu et al. type A2 congenital thumb duplication and implications for management: new subtypes and surgical strategies.}, journal = {Frontiers in pediatrics}, volume = {13}, number = {}, pages = {1536872}, pmid = {40129698}, issn = {2296-2360}, abstract = {OBJECTIVE: This study aimed to assess the radiographic features of patients diagnosed with congenital thumb duplication (CTD) type A2 based on the Wu et al. classification, describe the different subtypes of duplications and propose a classification system that permits identifying various surgical strategies.

METHODS: We evaluated 665 patients (680 thumbs) diagnosed with type A2 CTDs by examining the alignment of the interphalangeal (IP) and metacarpophalangeal (MP) joints of the primary thumb on posteroanterior (PA) radiographs. The classification system has four types: Type I (no deviation); Type II (ulnar deviation); Type III (hypertrophic epiphysis); and Type IV (convergent). Types I-IV were compared to Hung et al.'s system Type A-D (Hypoplastic, Ulnar Deviation, Divergent, and Convergent).

RESULTS: Of the 680 fingers, 436 (64.1%) were determined to be Wassel type IV while 244 (35.9%) were classified as Wassel type VII. All of the 436 fingers could be categorized according to the subtypes of the Hung et al. system; in particular, 369 (84.6%) were identified as type B, 52 (11.9%) as type D, and 15 cases (3.4%) as type C. The proposed classification system worked effectively for all CTDs (n = 680). 494 cases were classified as type II (72.6%), while 75 cases were classified as type I (11.0%). The remaining 111 cases were further classified as either type IV (9.3%) or type III (7.1%). The Wu et al. systems showed excellent intra-rater (0.881) and inter-rater (0.873) reliability compared to the Hung et al. systems (0.842 and 0.823, respectively).

CONCLUSIONS: The proposed radiographic pathoanatomical system has the potential to improve communication and guide optimal procedure selection for different subtypes of CTD depending on the attachment of the extra digit to the main thumb and the alignment of the interphalangeal and metacarpophalangeal joints of the primary thumb (Wu et al. type A2).

LEVEL OF EVIDENCE: III.}, } @article {pmid40126301, year = {2025}, author = {Sohn, J and Rochester, E and Oluyase, AO}, title = {Features of COPD That Lead to Stigmatisation and Its Consequences: A Framework Synthesis.}, journal = {COPD}, volume = {22}, number = {1}, pages = {2476435}, doi = {10.1080/15412555.2025.2476435}, pmid = {40126301}, issn = {1541-2563}, mesh = {Humans ; *Pulmonary Disease, Chronic Obstructive/psychology ; *Social Stigma ; Smoking/psychology ; Patient Acceptance of Health Care/psychology ; Qualitative Research ; Social Isolation ; }, abstract = {COPD is a highly stigmatised condition. To develop effective measures to reduce COPD-related stigma, it is important to understand patients' experiences and identify contributing factors. This systematic review explores qualitative evidence regarding the features of COPD leading to stigmatisation and how it can potentially influence health outcomes. Electronic databases were searched to identify primary qualitative studies focussing on stigma-related experiences of adults with COPD, published between January 1988 to August 2024. Data were synthesised using framework synthesis. Twenty-nine studies with 427 participants were included in this review. Findings fit well into six themes identified from Jones et al.'s framework of stigma dimensions and provide rich description. Smoking habit was not the only factor of stigma but also factors that contributed to disability of individuals. Patients experience COPD-related stigma mainly from themselves and healthcare professionals. Potential consequences of stigma identified are mental distress, isolation, reduced help-seeking behaviour and non-compliance to management. Collective effort by society and healthcare systems will be necessary to alleviate the stigma associated with chronic symptoms and smoking behaviour of COPD and to promote the benefit of pulmonary rehabilitation and available mental health support.}, } @article {pmid40125926, year = {2025}, author = {Hung, YC and Wei, LC}, title = {Letter to the Editor: Integrating context-specific and universal strategies: reflections on Birrell et al.'s universal school-based mental health interventions.}, journal = {Child and adolescent mental health}, volume = {}, number = {}, pages = {}, doi = {10.1111/camh.12778}, pmid = {40125926}, issn = {1475-357X}, abstract = {This letter responds to Birrell et al.'s (Child and Adolescent Mental Health, 30, 92) article on universal school-based mental health interventions, emphasizing the importance of refining universal approaches rather than discarding them. The letter discusses critical aspects of program adaptation to cultural contexts, the role of meaningful co-design with students and staff, and the integration of targeted strategies in concert with universal approaches. It also highlights the potential of digital health technologies, emphasizing equitable access and personalization to diverse populations. Additionally, the letter calls for a broader evaluation of intervention impacts beyond symptom reduction, including stigma reduction, school climate, and help-seeking behaviors. Drawing from recent evidence, the letter advocates for integrated models that combine universal and targeted strategies, offering practical recommendations for future research and policy.}, } @article {pmid40125382, year = {2024}, author = {Davis, DA and Casper, MJ and Hammonds, E and Post, W}, title = {The Continued Significance of Obstetric Violence: A Response to Chervenak, McLeod-Sordjan, Pollet et al.}, journal = {Health equity}, volume = {8}, number = {1}, pages = {513-518}, pmid = {40125382}, issn = {2473-1242}, abstract = {This guest editorial offers a critical response to Chervenak, McLeod-Sordjan, Pollet et al.'s clinical opinion dismissing obstetric violence as both emotionally charged and damaging to provider-patient relationships. We assert that obstetric violence remains a significant and useful framework to name and challenge racist, misogynist, and harmful medical practices. We note that such harmful practices are embedded in systems and cannot be addressed merely by individual physicians or shifts in the provider-patient relationship. Throughout, we situate the term obstetric violence in historical and legal context and demonstrate its continuing relevance to contemporary reproductive health care.}, } @article {pmid40120071, year = {2025}, author = {Robinson, OC and Richards, SH and Shoesmith, E and Pini, S and Fallon, M and Mulvey, MR}, title = {Contextual Adaptation of a Complex Intervention for the Management of Cancer Pain in Oncology Outpatient Services: A Case Study Example of Applying the ADAPT Guidelines.}, journal = {Psycho-oncology}, volume = {34}, number = {3}, pages = {e70132}, pmid = {40120071}, issn = {1099-1611}, support = {RA/2019/R1/001/YCR_/Yorkshire Cancer Research/United Kingdom ; }, mesh = {Humans ; *Cancer Pain/therapy/diagnosis/drug therapy ; *Pain Management/methods/standards ; *Pain Measurement/methods/standards ; United Kingdom ; Outpatients ; Practice Guidelines as Topic ; *Ambulatory Care ; *Neoplasms/complications ; Quality of Life ; }, abstract = {OBJECTIVES: Standardising pain assessment in oncology outpatient services (OOS) leads to improvements in patients' pain and quality of life. The Edinburgh Pain Assessment Tool (EPAT) is a standardised cancer pain management tool that has been implemented on inpatient oncology wards (the original setting). Routine use of EPAT reduced post-surgical pain in cancer patients (the original scenario) and led to more appropriate analgesic prescribing. We describe here a case study of adapting the EPAT intervention for use in tertiary OOS in the United Kingdom (UK) National Health Services (NHS), using the ADAPT guidelines.

METHODS: The adaptation process followed Moore et al.'s ADAPT guidance: Step 1: We assessed rationale for adapting EPAT by reviewing existing literature of pain management in OOS. Step 2: Semi-structured interviews with 20-healthcare professionals (HCPs) to understand current practice and how the intervention might fit the new context (OOS). Step 3: Identified the 'core' and 'peripheral' components of EPAT, undertook four co-design workshops with 7-HCPs to reconfigure EPAT to fit OOS (adapted version is referred to as EPAT+). Four HCPs trialled the EPAT+ intervention in practice to refine the intervention.

RESULTS: Combining qualitative data from interviews with feedback from the co-design workshops and preliminary testing the prototype intervention highlighted several key adaptation goals for EPAT+. These included: (1) reduce length/time to complete EPAT+ due to time constraints in outpatient appointments, (2) the importance of pain re-assessment and using EPAT to facilitate patients to self-monitor their pain at home, and (3) the creation of new peripheral components to support communication with primary care providers.

CONCLUSIONS: Using a theoretical driven conceptual guidance provided important learning on how to adapt an existing cancer pain management tool to a new setting (OOS). The result is a novel complex theory- and evidence-based intervention that will be formally tested in a cluster randomised pilot trial.}, } @article {pmid40116286, year = {2025}, author = {Cleverley, K and Salman, S and Davies, J and Ewing, L and McCann, E and Sainsbury, K and Gray, M and Lau, CKY and Lipsitz, O and Prompiengchai, S}, title = {Frameworks Used to Engage Postsecondary Students in Campus Mental Health Research: A Scoping Review.}, journal = {Health expectations : an international journal of public participation in health care and health policy}, volume = {28}, number = {2}, pages = {e70144}, pmid = {40116286}, issn = {1369-7625}, support = {//This research was supported by a grant from the Connaught Global Challenge Award at the University of Toronto awarded to K.C./ ; }, mesh = {Humans ; *Students/psychology ; *Mental Health ; Universities ; }, abstract = {BACKGROUND: There is an increasing prevalence of mental health concerns reported among postsecondary students (PSS) and growing demands for care on campuses around the world, as such there is an urgent need for research and innovations in PSS mental health that engages PSS. However, best practices and guidelines for facilitating PSS engagement in research is lacking. To address this gap, we undertook this review to explore frameworks used for engaging with PSS in research focused on PSS mental health.

METHODS: A scoping review of the academic literature was conducted. Frameworks used to engage PSS in mental health research were identified and categorized using the taxonomy of patient and public engagement by Greenhalgh et al. A list of barriers and facilitators to engaging with PSS was also identified and reported.

RESULTS: Of the articles assessed for full-text screening (n = 167), 26 journal articles were included. Frameworks used for engaging PSS in mental health research were classified into one of the three categories from Greenhalgh et al.'s taxonomy: study-focused (n = 14), partnership-focused (n = 9) and power-focused (n = 3). No relevant frameworks were found for two categories: priority- and report-focused. Seven documents reported relational or process-related barriers and/or facilitators to engaging with PSS. Based on these findings, recommendations were drafted with PSS advisors on how to implement an engagement framework in PSS mental health research.

CONCLUSIONS: We identified existing practices outlined within frameworks used to engage PSS and barriers and facilitators to engage with PSS in mental health research. Based on the review findings and PSS advisors recommendations, a need for developing a comprehensive engagement framework specific to the PSS context was identified.

The research team led consultations with a PSS advisory group for this review. Student advisors were actively engaged in data analysis, which included categorizing and drafting of recommendations, and the preparation of this manuscript.}, } @article {pmid40114332, year = {2025}, author = {Yildirim, JG and Lawn, S}, title = {Psychometric Properties of the Turkish Version of the Partners in Health Scale: Chronic Disease Self-Management in Primary Healthcare.}, journal = {International journal of nursing practice}, volume = {31}, number = {2}, pages = {e70007}, pmid = {40114332}, issn = {1440-172X}, mesh = {Humans ; Turkey ; *Psychometrics ; *Primary Health Care ; Female ; Middle Aged ; Male ; Aged ; Cross-Sectional Studies ; Adult ; Chronic Disease/therapy ; Aged, 80 and over ; *Self-Management ; Reproducibility of Results ; Surveys and Questionnaires ; *Self Care ; }, abstract = {BACKGROUND: This study aimed to assess the psychometric properties of the Turkish version of the Partners in Health Scale (PIH-TR), which was developed to assess the perceptions of patients with chronic conditions in primary care. Accurate assessment of facilitators and barriers to self-management of chronic conditions, from the patients' perspective, is important for working effectively with them to promote better health outcomes.

METHODS: A cross-sectional validation study was conducted and designed according to the STROBE guidelines. One hundred thirty-six patients, aged 30-90 years (86.7% aged > 60), were recruited from family care centres. Data were collected using the revised PIH, an adapted version of Model-2 (PIH-TR), which is a 12-item self-rated measure of self-management of chronic conditions. The PIH was translated into Turkish using Beaton et al.'s method. Content, construct validity and internal consistency analyses were undertaken to evaluate the data.

RESULTS: The PIH-TR had satisfactory reliability and validity and revealed a four-factor structure appropriate to the original scale: knowledge, partnership in treatment, recognition and management of symptoms and coping. Omega coefficient (0.860), test-retest reliability (0.841) and comparative fit indices (CFI) (0.99) were high.

CONCLUSION: The PIH-TR has good specifics and is reliable and valid as an objective self-rated tool to assess self-management of Turkish patients' chronic conditions.}, } @article {pmid40114110, year = {2025}, author = {Anderson, T and Mitchell, G and Prue, G and McLaughlin, S and Graham-Wisener, L}, title = {The psychosocial impact of pancreatic cancer on caregivers: a scoping review.}, journal = {BMC cancer}, volume = {25}, number = {1}, pages = {511}, pmid = {40114110}, issn = {1471-2407}, mesh = {Humans ; *Caregivers/psychology ; *Pancreatic Neoplasms/psychology/therapy ; Quality of Life ; *Stress, Psychological/psychology ; }, abstract = {BACKGROUND: Family caregivers are essential members of the care team of someone with pancreatic cancer, supporting their physical and psychological needs. Caregivers are often unprepared for this which may cause substantial psychosocial impact. This may be exacerbated by the short life-expectancy and rapid deterioration associated with pancreatic cancer. A scoping review was conducted to identify, from the existing literature, what is currently known about the psychosocial impact of pancreatic cancer on caregivers across the disease trajectory.

METHODS: A Joanna Briggs Institute (JBI) mixed methods scoping review was conducted across four databases (CINAHL, EMBASE, MEDLINE, PsycINFO). All identified citations were uploaded to Covidence, and were screened independently by two reviewers. Data were extracted and synthesised following a deductive approach guided by 'The Cancer Family Caregiving Experience' model (Fletcher et al., 2012).

RESULTS: 42 studies were included: 22 qualitative, 15 quantitative, 5 mixed methods. Results of the included studies were collated into the proposed constructs of Fletcher et al.'s (2012) model: primary stressors, secondary stressors, appraisal, cognitive-behavioural responses, health and wellbeing outcomes, as well as the influence of disease trajectory and contextual factors. The literature highlighted pancreatic cancer caregivers experienced stress related to caregiving activities, disruptions in their daily life and family relationships, high levels of unmet need, and poorer quality of life compared to other cancer caregivers. They were also at increased risk for various psychiatric disorders and reported a persistent lack of support which exacerbated the psychosocial impact.

CONCLUSIONS: Pancreatic cancer caregivers experience negative psychosocial impacts, exacerbated by the disease's trajectory. Feelings of a lack of support were reflected throughout the included literature and emphasise the need for future research into how pancreatic cancer caregivers may be best supported, and sign-posted to existing support, to minimise the substantial psychosocial impact they may experience.}, } @article {pmid40110864, year = {2025}, author = {Kornhaber, R and Mc Kittrick, A and Rossiter, R and Cleary, M}, title = {Pain experiences in adult burn survivors during rehabilitation and recovery: A qualitative systematic review.}, journal = {Journal of burn care & research : official publication of the American Burn Association}, volume = {}, number = {}, pages = {}, doi = {10.1093/jbcr/iraf031}, pmid = {40110864}, issn = {1559-0488}, abstract = {Despite advancements in burn care, pain persists despite multidisciplinary management efforts. This review aimed to synthesise the qualitative research that explored the impact of pain on burn survivors' rehabilitation and recovery. In September 2023, PubMed, CINAHL, and Scopus were searched for peer-reviewed published research in English. Nineteen articles from 17 studies met the inclusion criteria. The review used Thomas and Harden's thematic synthesis framework for qualitative research evidence. Two descriptors of pain were described, physical and psychological pain. Pain in burn survivors, both physical and psychological, was complex, intertwined, and dynamic across three stages: before, during, and after interventions. This was found to closely align with Cleary et al.'s trauma-informed model of care in burn settings, which emphasises a three-stage process, underlining that pain is not static but evolves and fluctuates, necessitating adaptive and patient-centred burn care and post-treatment mental health support. Adopting a Trauma-Informed Care (TIC) approach in burn injury settings is crucial. Individuals post-burn encounter varying degrees of physical and psychological pain, which for some remains persistent. Using patient-reported measures throughout recovery deepens the understanding of burn survivors' pain, respecting their personal experiences and insights. It is essential to conduct future longitudinal research and push for a burn-specific qualitative pain assessment to address these complex needs effectively.}, } @article {pmid40107852, year = {2025}, author = {Galaitsi, SE and Trump, BD and Cline, EH and Kitsak, M and Linkov, I}, title = {Navigating the precipice: Lessons on collapse from the Late Bronze Age.}, journal = {Risk analysis : an official publication of the Society for Risk Analysis}, volume = {}, number = {}, pages = {}, doi = {10.1111/risa.70019}, pmid = {40107852}, issn = {1539-6924}, support = {Laboratory Enhancements (FLEX-4) Program//US Army Corps of Engineers/ ; }, abstract = {Around 1200 BCE, the societies of the Late Bronze Age (LBA) in the Eastern Mediterranean experienced a collective collapse, evident in the archeological remains of destroyed and abandoned cities. Following our prior explorations in this topic, we hypothesize that the network structure between the LBA societies amplified compounding threats, producing a cascade of failures that culminated in a precipitous broad systemic collapse. The network, so often seen as a conduit for prosperity, propagated the problems of individual nodes. Herein we discuss the findings of Linkov et al.'s (2024) network analysis of the LBA collapse and its implications regarding vulnerabilities in our current global context as our systems surpass carrying capacity in our pursuit of societal complexity.}, } @article {pmid40090827, year = {2025}, author = {Giordana, JY and Caci, H}, title = {Stigma by association revealed in a survey conducted among UNAFAM members.}, journal = {L'Encephale}, volume = {51}, number = {4}, pages = {429-436}, doi = {10.1016/j.encep.2024.12.007}, pmid = {40090827}, issn = {0013-7006}, mesh = {Humans ; Female ; Male ; *Social Stigma ; Adult ; Middle Aged ; *Mental Disorders/psychology ; Young Adult ; Adolescent ; *Family/psychology ; Surveys and Questionnaires ; Aged ; Factor Analysis, Statistical ; Psychometrics ; Prejudice/psychology ; }, abstract = {BACKGROUND: Stigma by association (also known as secondary, family, or courtesy stigma) adds to public stigma and self-stigma. First described by Erwin Goffman in 1963, it affects those close to stigmatized individuals, particularly people with mental health conditions. King et al.'s scale from 2007 models public stigma based on three components: Discriminatory Reactions, Disclosure Concerns, and Positive Aspects.

METHOD: King's scale was adapted for use by family members and administered through UNAFAM's (National Union of Families and Friends of People with Mental Health Conditions) online survey. The sample included 3650 participants (2962 women). Confirmatory and exploratory factor analyses were conducted to examine the scale's structure. We explored the effects of sex and kinship on factor scores using ANOVA/ANCOVA models.

RESULTS: While confirmatory factor analyses showed significant deviation from the original structure, exploratory analyses largely recovered the three original dimensions. The "Discrimination" dimension revealed experienced and perceived prejudice along with resulting reactions. The "Disclosure" dimension demonstrated persistent difficulties in discussing a family member's mental health condition due to fears of personal and professional consequences. The "Positive Aspects" dimension showed that respondents became more understanding and tolerant toward their family member with a mental health condition, although only 40% reported becoming more resilient through this experience.

CONCLUSIONS: The adapted King's scale can now be used to investigate determinants and consequences of stigma by association in other populations, including neurodevelopmental disorders (such as autism spectrum disorder and attention-deficit/hyperactivity disorder), schizophrenia, mood disorders, substance use disorders, and dementias.}, } @article {pmid40088786, year = {2025}, author = {Świsłowski, P and Hebda, G and Zinicovscaia, I and Chaligava, O and Isinkaralar, O and Isinkaralar, K and Rajfur, M}, title = {I believe I can fly… but in polluted air, why? Bird feathers as an example of environmental contaminant monitoring.}, journal = {The Science of the total environment}, volume = {972}, number = {}, pages = {179033}, doi = {10.1016/j.scitotenv.2025.179033}, pmid = {40088786}, issn = {1879-1026}, mesh = {Animals ; *Feathers/chemistry ; *Environmental Monitoring/methods ; *Air Pollutants/analysis/metabolism ; Female ; Male ; *Passeriformes/metabolism ; Principal Component Analysis ; }, abstract = {Metallic element pollution is a global environmental problem, and it is important to study various local conditions to understand the mechanisms on a larger scale. Environmental contamination can be studied in many ways, but non-destructive techniques and methods that preserve the sample are increasingly gaining attention, especially in relation to studies on living organisms. The present study aimed to analyze the feathers of the great tit (Parus major) for Al, S, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, Cd, Ba and Hg content. Discriminant analysis showed that according to elemental composition young females and males make separate groups. At the same time, old birds are in the same group. From principal component analysis (PCA), elements distribution depends on age and gender and sources of elements can be natural and anthropogenic. However, not all element accumulation was dependent on both parameters: Al, Cr, Fe, and Ni were statistically significant from both parameters. Bird feathers can be regarded as promising biomonitors of air quality.}, } @article {pmid40072597, year = {2025}, author = {Helton, WS}, title = {Perceptual decoupling in the sustained attention to response task is indeed unlikely: a reply to Shelat and Geisbrecht (in press).}, journal = {Experimental brain research}, volume = {243}, number = {4}, pages = {88}, pmid = {40072597}, issn = {1432-1106}, mesh = {Humans ; *Attention/physiology ; *Psychomotor Performance/physiology ; *Reaction Time/physiology ; }, abstract = {Shelat and Geisbrecht (in press) challenge Bedi et al.'s (Exp Brain Rese 242(8):2033-2040 2024b) position that perceptual decoupling in the Sustained Attention to Response Task (SART) is unlikely. Instead they argue perceptual decoupling is likely in the SART and advocate for the SART's continued use in perceptual decoupling research. Shelat and Geisbrecht, however, are overlooking the extensive behavioral evidence that perceptual decoupling in the SART is indeed unlikely, including research by the researchers who originally developed the task demonstrating nearly 100% awareness of the task stimuli. The SART was developed to be a very short replacement for the long duration low Go, high No-Go target detection tasks used by sustained attention or vigilance researchers. While altering the response format in the SART to a high Go, low No-Go task indeed resulted in errors occurring reliably in a very short duration, the resulting SART has a substantial speed-accuracy trade-off. This causes immense confusion when interpreting performance in the SART. Furthermore, Shelat and Geisbrecht suggest DeBettencourt et al. (Nat Hum Behav 3(8):808-816, 2019) as a method improvement on the original SART, but ignore the entire point of the SART which was to be a short duration replacement for traditional vigilance tasks. The task utilized by DeBettencourt et al. (Nat Hum Behav 3(8):808-816, 2019) is as long in duration or longer than traditional vigilance tasks, but still is contaminated with a speed-accuracy trade-off, which makes untangling the underlying processes involved challenging. If researchers want to study sustained attention- perceptual decoupling, vigilance researchers have already figured out how to do this and the way to do this is not the SART.}, } @article {pmid40075376, year = {2025}, author = {Bourke, L and Conway, C and Abdalla, ME}, title = {Mentorship in surgical training; a systematic scoping review to inform a mentorship framework for ophthalmology trainees.}, journal = {BMC medical education}, volume = {25}, number = {1}, pages = {373}, pmid = {40075376}, issn = {1472-6920}, mesh = {Humans ; *Ophthalmology/education ; *Mentors ; Clinical Competence ; }, abstract = {BACKGROUND: Mentorship plays a vital role in surgical training. In the field of ophthalmology, effective mentorship is particularly critical due to the specialised nature of surgeries and the need for comprehensive skill development. However, the landscape of mentorship remains underexplored. Understanding key characteristics and components of effective mentorship is essential for optimising training and ensuring the success of future generations of surgeons. This scoping review aims to analyse existing literature on mentorship in surgical training and to employ Levac et al.'s enhanced methodological framework to construct a conceptual framework for a bespoke mentorship programme tailored to the needs of ophthalmology trainees.

METHODS: The search strategy adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and included relevant databases such as MEDLINE, Scopus, CINAHL Complete, ERIC, EMBASE, and the Cochrane Library. Selection criteria encompassed studies exploring mentorship experiences, perceptions, and outcomes across all surgical training domains. A two-step screening process was employed, followed by thematic analysis using Braun and Clarke's approach. The Medical Education Research Study Quality Instrument (MERSQI) assessed study quality.

RESULTS: Of the 81 identified articles, 24 were included in the review, with an average MERSQI score of 11.65. Studies comprised randomised controlled trials, systematic reviews, cohort, cross-sectional studies, and reviews. The thematic analysis identified five domains: (1) mentorship and burnout; (2) surgical skill and performance; (3) career paths and professional development; (4) diversity promotion; and (5) work-life balance.

CONCLUSIONS: This review underscores the significance of mentorship in surgical training and proposes a conceptual framework tailored to ophthalmology trainees. By synthesising existing literature and through author engagement with relevant training bodies, the study contributes to the development of an imminent mentoring programme, aiming to enhance surgical training outcomes and foster trainee well-being and professional growth.}, } @article {pmid40070057, year = {2025}, author = {Holzner, A and Ruppert, N and Ilham, K and Kaburu, SSK and Koch Liston, AL and Fuentes, A and Hansen, MF}, title = {Threatened synanthropes depend on intact forests: a critical evaluation of Moore et al. (2023).}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {100}, number = {4}, pages = {1444-1451}, pmid = {40070057}, issn = {1469-185X}, support = {CF21-0473//Carlsberg Foundation/ ; //Animal Protection Denmark/ ; //Re:wild/ ; }, mesh = {Animals ; *Conservation of Natural Resources ; Ecosystem ; *Endangered Species ; *Forests ; *Presbytini/physiology ; Review Literature as Topic ; }, abstract = {Synanthropes are known for their remarkable adaptability to coexist with humans, yet increased visibility exposes them to significant threats, such as hunting or conflict over resources. Moore et al.'s review 'The rise of hyperabundant native generalists threatens both humans and nature' (https://doi.org/10.1111/brv.12985) explores distribution patterns and impacts of macaques and pigs in anthropogenic environments. Our critical evaluation of this study revealed several substantial issues: the pooling of data from species that are ecologically and behaviourally distinct, an error in data acquisition, potential biases in statistical analyses, and critical misrepresentations of threats to and from wildlife in human-impacted habitats. Additionally, we highlight the lack of evidence supporting the authors' core assertion of hyperabundance of the study species. While Moore et al. compare species densities and abundance across various habitat types, their analyses did not demonstrate population increases over time. On the contrary, our re-analysis of their data sets showed a decreasing population trend in Macaca nemestrina and the absence of M. fascicularis from 44% of surveyed habitats characterized by medium to high forest integrity. Further, our findings emphasize the importance of intact forests for predicting a high relative abundance of macaques and pigs. Overall, we recommend a more careful interpretation of the data, as misrepresentations of abundance data can result in negative or sensational discourses about overabundance, which may threaten the conservation of species that often thrive in anthropogenic landscapes.}, } @article {pmid40064766, year = {2025}, author = {Lewis, KA and Ray, P and Janibekyan, E and Kaushik, N and Anigol, D and Tieu, D and Luo, Z and Hernandez, L and Sen, A and Kumar, S and Fehrenbacher, AE and Swendeman, D}, title = {The Impact of the COVID-19 Pandemic and Lockdowns on Sex Workers in West Bengal, India.}, journal = {Journal of community health}, volume = {50}, number = {4}, pages = {668-681}, pmid = {40064766}, issn = {1573-3610}, support = {K01 TW012173/TW/FIC NIH HHS/United States ; }, mesh = {Humans ; *COVID-19/epidemiology/psychology ; India/epidemiology ; *Sex Workers/psychology/statistics & numerical data ; Female ; Male ; Adult ; Stress, Psychological ; Qualitative Research ; Social Isolation/psychology ; Interviews as Topic ; SARS-CoV-2 ; Young Adult ; Food Insecurity ; Pandemics ; }, abstract = {India's COVID-19 lockdowns were among the strictest globally, and sex workers were uniquely impacted. Extremely limited literature has examined pandemic consequences on sex workers. We use a qualitative approach to examine the impact of the COVID-19 pandemic and lockdowns on the lives and livelihoods of sex workers in urban West Bengal, India. Cisgender female and male, and transgender female sex workers (N = 40) participated in individual in-depth interviews. Interviews were coded using inductive thematic coding. Nine themes arose from the data: (1) COVID-19 pandemic and lockdowns, (2) Social isolation, (3) Lack of customers, (4) Financial stress, (5) Decreased negotiating power, (6) Food insecurity, (7) Receiving support, (8) Providing support, and (9) Mental health. We propose a Gendered Stress Proliferation Model incorporating Pearlin et al.'s 1997 conceptualization of stress proliferation and Swendeman, Fehrenbacher et al.'s 2018 gendered stress process model. In this model, primary stressors of COVID-19 pandemic and lockdowns proliferated into secondary stressors across multiple domains (social isolation, lack of customers, financial stress, food insecurity, reliance on support, decreased negotiating power). All of these pathways were shaped by pre-existing vulnerabilities and systems of intersectional marginalization. These stressors had significant mental health impacts including feelings of depression and anxiety. Food insecurity has implications for physical health outcomes, and financial stress coupled with decreased negotiating power has implications for sexual health, potentially placing sex workers at increased risk of sexually transmitted infections and HIV. Gendered Stress Proliferation may be a useful framework to examine how marginalized populations uniquely experience population-level crises.}, } @article {pmid40063458, year = {2025}, author = {Noah, N and Das, S}, title = {From PINs to Gestures: Analyzing Knowledge-Based Authentication Schemes for Augmented and Virtual Reality.}, journal = {IEEE transactions on visualization and computer graphics}, volume = {31}, number = {5}, pages = {3172-3182}, doi = {10.1109/TVCG.2025.3549862}, pmid = {40063458}, issn = {1941-0506}, abstract = {As Augmented and Virtual Reality (AR/VR) advances, secure and user-friendly authentication becomes vital. We evaluated 17 authentication schemes across gaze, gesture, PIN, spatial, and recognition-based categories using a systematic framework focused on effectiveness, security, and usability. Our analysis revealed varied performance and significant gaps requiring standardized methods. For example, Beat-PIN demonstrated strong security with 140-bit entropy, while RubikAuth achieved high usability with authentication times of 1.69 seconds. Gaze-based methods, though innovative, faced accuracy issues. We also observed a preference for schemes like In-Air Handwriting and Things, which balanced security and ease of use. By extending Bonneau et al.'s framework [5] to develop an AR/VR-specific evaluation model, we identified schemes like RubikAuth and Things as particularly promising for AR/VR. This study highlights the strengths and limitations of current methods and emphasizes the need for cross-modal and context-aware techniques to advance AR/VR authentication.}, } @article {pmid40060295, year = {2025}, author = {Ghonchehpour, A and Nasab, FRS and Maghsoudi, F and Mehdipour-Rabori, R}, title = {Existential Anxiety of Nurses in the COVID-19-Virus Units and Its Relation With Resilience and Posttraumatic Growth.}, journal = {Health science reports}, volume = {8}, number = {3}, pages = {e70547}, pmid = {40060295}, issn = {2398-8835}, abstract = {AIM: The study aimed to investigate the relationship between existential anxiety, posttraumatic growth, and resilience in nurses working in COVID-19units.

DESIGN: The study was a descriptive-analytical study.

METHODS: The researchers conducted the study on 224 nurses working in the COVID-19units of four hospitals affiliated with Kerman University of Medical Sciences in Southeast Iran from 2021 to 2020 with census method. the data were collected using a demographic questionnaire, Masoudi Sani et al.'s existential anxiety questionnaire, the Conner-Davidson resilience scale, posttraumatic growth inventory.

RESULTS: The mean age of nurses were 30.88% ± 6.53% and 76.3% of them were female. The results showed there were a negative and significant correlation between posttraumatic growth and resilience (p < 0.001, r = -0.38) but no statistically significant relationship between existential anxiety, resilience, and posttraumatic growth (p > 0.05). Regression analysis indicated a negative and significant relationship between posttraumatic growth and resilience, but no statistically significant relationship between existential anxiety, resilience (p = 0.28), and Posttraumatic growth (p = 0.20). There was no significant difference between the mean existential anxiety score, age, sex, and education level, but the mean existential anxiety score in the emergency personnel was significantly higher than of other departments.

CONCLUSION: The results demonstrated that the mean scores of existential anxiety, resilience and posttraumatic growth were moderate. The researchers suggest educational and interventional measures to improve resilience, posttraumatic growth and reduce existential anxiety among nurses.}, } @article {pmid40053085, year = {2025}, author = {Baffi, A and Crispiatico, V and Aiello, EN and Curti, B and De Luca, G and Poletti, B and Buratti, M and Montali, L}, title = {Cross-Cultural Adaptation and Preliminary Validation of the Italian Version of the Feeding-Swallowing Impact Survey for both Members of Parental Dyads.}, journal = {Dysphagia}, volume = {}, number = {}, pages = {}, pmid = {40053085}, issn = {1432-0460}, abstract = {The Feeding/Swallowing Impact Survey (FS-IS) is the first validated instrument to measure the impact of Pediatric Feeding Disorder (PFD) on their caregivers. This study aimed to translate and adapt the FS-IS into Italian (FS-IS-IT) and analyze its reliability and validity, for both fathers and mothers. The FS-IS-IT was developed using Beaton et al.'s 5-stage process. This cross-sectional study involved 32 dyads of parents of children with PFD and 15 dyads of caregivers of children with developmental disorders without PFD. Twenty caregivers completed the FS-IS-IT questionnaire twice to ensure test-retest reliability. All caregivers completed the Zarit Burden Inventory (ZBI) and the IDDSI Diet Functional Scale for construct validity analysis. ROC analysis was used to evaluating the diagnostic properties of FS-IS-IT in screening between dyads of children with PFD and dyads without these symptoms. The FS-IS-IT was reliable for both fathers and mothers, with satisfactory internal consistency (mothers' McDonald's ω=0.93; fathers' McDonald's ω=0.94) and test-retest reliability (intraclass correlation coefficient > 0.97). Moderate-to-strong statistically significant correlations (mothers: r(32)=0.73; p =.018; fathers: r(32)=-0.42; p=.018). r(32)=-0.41; p=.018). The FSIS-IT was featured by optimal diagnostics (mothers: AUC=0.97; fathers: AUC=0.94), a cut-off of 1.58 for mothers and 1.65 for fathers has shown good specificity and sensitivity. The FS-IS-IT is a reliable and valid tool for the assessment of the impact of PFD and shows optimal diagnostic properties.}, } @article {pmid40047392, year = {2025}, author = {Alkaabi, O and Babenko-Mould, Y and Kerr, M and Cranley, L and Aboshaiqah, A}, title = {Testing the psychometric properties of the Authentic Leadership Questionnaire among nurses in Saudi Arabia.}, journal = {Leadership in health services (Bradford, England)}, volume = {38}, number = {2}, pages = {318-333}, doi = {10.1108/LHS-05-2024-0049}, pmid = {40047392}, issn = {1751-1887}, mesh = {Saudi Arabia ; Psychometrics ; Humans ; Surveys and Questionnaires ; *Leadership ; Female ; Male ; Adult ; Reproducibility of Results ; *Nursing Staff, Hospital/psychology ; }, abstract = {PURPOSE: This paper aims to evaluate the psychometric properties of the "rater" version of the Authentic Leadership Questionnaire in nursing practice within the context of Saudi Arabia.

DESIGN/METHODOLOGY/APPROACH: The analysis of the psychometric properties of Avolio et al.'s Authentic Leadership Questionnaire (2007). This version of the Authentic Leadership Questionnaire was in the English language. A convenience sampling method was used to obtain data from 215 Saudi early career nurses working at public hospitals affiliated with the Ministry of Health in Saudi Arabia. Data analysis included assessing internal consistency (Cronbach's alpha) analysis and the exploratory factor analysis using the Statistical Package for Social Sciences version. Face and content validity were evaluated using a content validity index, and Mplus was also used to assess the factor structure of the Authentic Leadership Questionnaire by conducting confirmatory factors analysis.

FINDINGS: The results of psychometric testing of the Authentic Leadership Questionnaire provide initial support for the content and construct validity and internal reliability of the instrument among early career nurses in Saudi Arabia.

ORIGINALITY/VALUE: The results supported that the 16 items of the rater's version of the Authentic Leadership Questionnaire measure nurses' perceptions of the authentic leadership of their leaders. The psychometric properties of the Authentic Leadership Questionnaire yield a valuable contribution to empirical research within the nursing population. The results of this study suggest that the Authentic Leadership Questionnaire will be useful for health service researchers and nursing leaders seeking to understand and capture authentic leadership qualities in Saudi Arabia.}, } @article {pmid40035928, year = {2025}, author = {Amos, J and Moase, J and Sladeczek, IE}, title = {A scoping review of school-based expressive writing implementation reporting practices: missed opportunities and new research directions.}, journal = {Discover mental health}, volume = {5}, number = {1}, pages = {27}, pmid = {40035928}, issn = {2731-4383}, abstract = {BACKGROUND: Expressive writing (EW) interventions are an effective, flexible, and cost-efficient option for mental health promotion, making them ideally suited for resource-limited school settings. However, the effectiveness of EW interventions varies greatly across studies, which may be partly explained by how EW interventions are implemented. As school-based EW interventions become increasingly popular and more widely used, rigorous reporting of implementation can help advance this emerging field by informing how variation in implementation across studies influences intervention outcomes.

PURPOSE: The purpose of this scoping review was to evaluate the implementation reporting practices of EW interventions in school settings as they can profoundly impact EW effectiveness.

METHODS: The present scoping review assessed the current state of fidelity of implementation (implementation) reporting in the school-based EW literature and identified areas where more rigorous reporting is needed. Out of an initial sample of 367 studies, 19 were eligible for inclusion in the review. Data were analyzed for critical issues and themes derived from Cargo et al.'s (2015) Checklist for Implementation (Ch-IMP).

RESULTS: Overall, the results of this scoping review indicate that researchers who implement EW in school settings have not consistently assessed key implementation domains such as dose received and fidelity.

CONCLUSIONS: To address this problem, the present review adds a unique contribution to the literature by identifying how rigorous reporting of implementation can strengthen the evidence base for school-based EW interventions. Specifically, researchers can support the use of EW interventions in schools through increased implementation reporting to better understand how variability in fidelity of implementation affects treatment outcomes.}, } @article {pmid40035360, year = {2025}, author = {Li, X and Yang, H}, title = {Capturing Forest Ecosystem Dynamics After Disturbances: From Individual Trees to Landscapes.}, journal = {Global change biology}, volume = {31}, number = {3}, pages = {e70107}, doi = {10.1111/gcb.70107}, pmid = {40035360}, issn = {1365-2486}, support = {42401105//National Natural Science Foundation of China/ ; }, mesh = {*Forests ; *Trees/physiology ; *Climate Change ; *Ecosystem ; Conservation of Natural Resources ; }, abstract = {Adopting a multiscale perspective that connects forest dynamics from tree stands to landscapes is crucial for understanding how forest ecosystems will evolve under global environmental change. This commentary highlights the significance of Perret et al.'s (2025) study in providing valuable insights into how individual tree plasticity drives community reorganization and ultimately alters ecosystem resilience, via integrating individual tree species into community-level analyses. Their study has important implications for modeling and predicting forest resilience, as well as for informing sustainable management strategies in response to future climate change and increasing disturbances.}, } @article {pmid40033513, year = {2025}, author = {Evans, SC and Althoff, RR}, title = {On the regulation and dysregulation of emotions in child psychopathology: commentary on Blader et al. (2025).}, journal = {Journal of child psychology and psychiatry, and allied disciplines}, volume = {66}, number = {4}, pages = {595-598}, pmid = {40033513}, issn = {1469-7610}, support = {R01 MH124965/MH/NIMH NIH HHS/United States ; }, mesh = {Adolescent ; Child ; Humans ; *Affective Symptoms/physiopathology ; *Emotional Regulation/physiology ; *Mental Disorders/physiopathology ; }, abstract = {Blader et al.'s (2025) recent annual review article makes an important contribution to the literature on emotion dysregulation in child and adolescent mental health. In addition to synthesizing the current evidence base, the authors put forth a cogent formalized view of emotion regulatory processes and how they go awry. Much has been written on emotion (dys)regulation and psychopathology (for overviews, see Lincoln et al., 2022; Paulus et al., 2021; Sheppes et al., 2015). It would therefore be reasonable to ask what novel contribution could be made by a new review article at this time. But for all that has been written, there is much work still to be done. Blader et al. (2025) admirably rise to meet this challenge. We hope this commentary amplifies and adds to their effort. Below, we reflect on a few aspects of their contribution and offer some further thoughts that may inform future work in this area.}, } @article {pmid40032540, year = {2025}, author = {Norris, P and George, M and Symon, V and Keown, S and Bhawan, S and Richard, L and Richards, R}, title = {Does access to medicines differ from access to healthcare? Experiences of barriers to medicines access by people facing social disadvantage.}, journal = {Research in social & administrative pharmacy : RSAP}, volume = {21}, number = {6}, pages = {480-486}, doi = {10.1016/j.sapharm.2025.02.010}, pmid = {40032540}, issn = {1934-8150}, mesh = {Humans ; *Health Services Accessibility ; Longitudinal Studies ; Female ; New Zealand ; Male ; Middle Aged ; Adult ; Refugees ; Communication Barriers ; Qualitative Research ; *Prescription Drugs ; }, abstract = {BACKGROUND: Levesque et al.'s widely-cited five dimensional model of access to healthcare has been used in a variety of contexts, including access to medicines. However the model is based on healthcare, i.e., facilities where health professionals work. We examined whether there were other important features of access to medicines, not captured by this model.

METHODS: A longitudinal qualitative study was conducted, repeatedly interviewing 21 households about their lives and access to medicines, over the course of a year. Participants were Māori, Pacific, former refugee, or New Zealand Europeans with limited incomes. Analysis was thematic and inductive.

RESULTS: Our participants experienced a number of barriers to accessing medicine, some of which do not fit comfortably within existing models of access to healthcare. For example, communication difficulties with healthcare staff (lack of appropriateness of care), had implications for medicine-taking after participants got home. Confusion about medicines identity, purpose and possible side effects, led to poorer access or under-use of prescribed medicines. Communication problems were particularly acute for former refugee participants. For them, communication in pharmacies was impossible because of lack of interpreters, severely restricting the information they had access to, and increasing the use of other less reliable sources of information. Crime, fear of crime, and the justice system also impacted on access in a variety of ways.

CONCLUSION: Because medicines are portable, physical objects taken at home, the effects of appropriateness of healthcare are played out in the home. Aspects of the wider, non-healthcare environment also impact on access to medicines in unexpected ways.}, } @article {pmid40032170, year = {2025}, author = {Placidi, E and Fionda, B and Rosa, E and Tagliaferri, L and De Spirito, M}, title = {Commentary on feliciani Giacomo et al.'s study of comparison of HDR-brachytherapy and tomotherapy for the treatment of non-melanoma skin cancers of the head and neck.}, journal = {Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology}, volume = {206}, number = {}, pages = {110826}, doi = {10.1016/j.radonc.2025.110826}, pmid = {40032170}, issn = {1879-0887}, } @article {pmid40029574, year = {2025}, author = {Belsti, Y and Mousa, A and Jackson, H and Moran, LJ and Palmer, KR and Dhungana, RR and Callander, E and Rolnik, DL and Teede, H and Enticott, J}, title = {Authors' response to Tran et al.'s comment on "The Use of Multiple Medications During Pregnancy Among an Ethnically Diverse Population in South-Eastern Melbourne: A Retrospective Analysis to Explore Potential Risks and Complications".}, journal = {Drug safety}, volume = {48}, number = {4}, pages = {439-441}, pmid = {40029574}, issn = {1179-1942}, } @article {pmid40027280, year = {2025}, author = {Gesualdo, P and Melin, J and Karban, R and Crouch, C and Killian, M and Hopkins, D and Adamsson, A and Stock, J and Johnson, SB and Baxter, J and , }, title = {Structures and strategies for retaining an international pediatric cohort from birth: Lessons from The Environmental Determinants of Diabetes in the Young (TEDDY) study.}, journal = {Contemporary clinical trials communications}, volume = {44}, number = {}, pages = {101405}, pmid = {40027280}, issn = {2451-8654}, abstract = {BACKGROUND: Retention of study participants in observational studies is essential to maintaining the representativeness of the population, minimizing selection bias, and assuring sufficient statistical power. The aim of this report is to describe the structures and strategies used to retain participants in The Environmental Determinants of Diabetes in the Young (TEDDY) Study, an observational study of children at increased genetic risk for type 1 diabetes followed in an intensive protocol from birth until age 15.

METHODS: Teague et al.'s systematic review of study retention strategies identified four domains: barrier reduction; community building; follow-up/reminder; and tracing strategies (1). TEDDY retention strategies were categorized into each of these domains. A fifth category presented strategies unique to TEDDY.

RESULTS: TEDDY employed over one hundred retention strategies during the 15 years of follow-up; many could be categorized within the Teague domains. Strategies unique to TEDDY included (1) study structures to support retention; (2) risk communication and education strategies specific to this population; (3) Data-informed retention strategies that addressed protocol challenges in real-time; and (4) implementation of a re-engagement protocol for those who had withdrawn from the study.

CONCLUSION: Pediatric cohort studies should include strategies, structures, and resources to address retention at the study's initiation and on an ongoing basis. Retention strategies should not remain static but change with the developmental needs of the child. Collecting and analyzing data on an ongoing basis permits retention strategies to be put in place to address protocol and retention challenges in real time.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00279318.}, } @article {pmid40025745, year = {2025}, author = {Norén, L and Bergström, M and Wallander, L}, title = {Coming to Terms with Risk Factors for Intimate Partner Violence Perpetration: A Scoping Review.}, journal = {Journal of evidence-based social work (2019)}, volume = {22}, number = {4}, pages = {469-498}, doi = {10.1080/26408066.2025.2469670}, pmid = {40025745}, issn = {2640-8074}, mesh = {Humans ; *Intimate Partner Violence/statistics & numerical data/prevention & control/psychology ; Risk Factors ; Female ; Male ; }, abstract = {PURPOSE: Intimate partner violence (IPV) is a global issue requiring a thorough understanding of risk factors to inform prevention strategies. This study applies Kraemer et al.'s (2005) categorization system to classify risk factors for IPV perpetration, addressing two research questions: 1) What variables or attributes are commonly employed to assess the risks associated with IPV perpetration, and how can these be thematized? 2) Which non-correlates, correlates, fixed markers, variable markers, and causal risk factors related to IPV perpetration are identified and examined in the existing literature?

MATERIAL AND METHODS: A scoping review of 62 publications on risk factors for IPV perpetration in married- and cohabiting couples was conducted. Risk factors were categorized using Kraemer et al.'s (2005) system.

RESULTS: The risk factors were classified into eight themes based on their shared characteristics. All variables fit Kraemer et al.'s categorization system. The majority showed correlational relationships. Fixed markers appeared in two themes, while variable markers appeared in six themes, however publications on these were limited. No causal risk factors were found.

DISCUSSION: The risk categorization system by Kraemer et al. enhances understanding of IPV perpetration risk factors. Priority areas for preventing IPV include reducing the risk of experiencing violence in childhood and ensuring access to higher education. More longitudinal research is needed for the remaining categories to establish temporal relationships.

CONCLUSION: The study highlights the value of Kraemer et al.'s categorization system for distinguishing correlation from causality in IPV risk factors, advancing prevention efforts. Important areas for preventive measures were targeted.}, } @article {pmid40024817, year = {2025}, author = {Zheng, C and Du, C and Lv, J}, title = {Improving screening participation: The need for socioeconomic considerations and psychological interventions in colorectal cancer programs.}, journal = {Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver}, volume = {57}, number = {6}, pages = {1331-1332}, doi = {10.1016/j.dld.2025.02.005}, pmid = {40024817}, issn = {1878-3562}, mesh = {Humans ; *Colorectal Neoplasms/diagnosis/psychology ; *Early Detection of Cancer/psychology ; Socioeconomic Factors ; *Mass Screening/psychology ; *Patient Compliance/psychology ; Healthcare Disparities ; }, abstract = {This correspondence discusses Silva et al.'s study on colorectal cancer (CRC) screening adherence and preferences, highlighting its contributions to understanding screening education, method choices, and barriers. While acknowledging the study's insights, we identify critical limitations, including insufficient consideration of socioeconomic disparities in screening access and participation. Lower socioeconomic groups often face barriers such as financial constraints, time limitations, and healthcare mistrust, which may skew adherence outcomes. Additionally, the study overlooks post-screening psychological impacts (e.g., anxiety from false positives) on long-term compliance. We propose integrating socioeconomic analyses, psychological interventions, and technological innovations (e.g., AI-driven tools for personalized reminders and counseling) to enhance screening equity and adherence. Future research should prioritize these dimensions to optimize CRC screening strategies globally.}, } @article {pmid40023051, year = {2025}, author = {Gastaldon, S and Calignano, G}, title = {Linguistic alignment with an artificial agent: A commentary and re-analysis.}, journal = {Cognition}, volume = {259}, number = {}, pages = {106099}, doi = {10.1016/j.cognition.2025.106099}, pmid = {40023051}, issn = {1873-7838}, mesh = {Humans ; *Psycholinguistics ; Reaction Time/physiology ; Semantics ; *Concept Formation/physiology ; *Pattern Recognition, Visual/physiology ; *Linguistics ; }, abstract = {In this manuscript we provide a commentary and a complementary analysis of Cirillo et al.'s (2022) study on conceptual alignment in a joint picture naming task involving a social robot (Cognition, 227, 105,213). In their study, Cirillo and collaborators present evidence suggesting automatic alignment by examining response proportions, reflecting adaptation to the lexical choices made by the artificial agent (i.e., providing category names instead of basic names for specific semantic categories). Here, we conducted a complementary analysis using the openly available dataset, employing a multiverse approach and focusing on response times as a more nuanced measure of cognitive processing and automaticity. Our findings indicate that alignment in the Category condition (i.e., when the robot provided a superordinate label) is associated with longer response times and greater variability. When providing the basic label in the Basic condition, RTs are much shorter and variability is reduced, compatible with the Basic-level advantage phenomenon. Non-alignment to each condition completely reverses the pattern. This suggests that aligning when producing a superordinate label is a strategic and effortful rather than an automatic response mechanism. Furthermore, through comprehensive visual exploration of response proportions across potentially influential variables, we observed category naming alignment primarily emerging in specific semantic categories, and mostly for stimuli with basic labels at low lexical frequency and newly designed pictures not taken from the MultiPic database, thus suggesting a limited generalizability of the effect. These insights were confirmed using leave-one-out robustness checks. In conclusion, our contribution provides complementary evidence in support of strategic rather than automatic responses when aligning with Category labels in the analyzed dataset, with a limited generalizability despite all the balancing procedures the authors carefully implemented in the experimental material. This is likely to reflect individual task strategies rather than genuine alignment. Lastly, we suggest directions for future research on linguistic alignment, building on insights from both Cirillo et al.'s study and our commentary. We also briefly discuss the Open Science principles that shaped our approach to this work.}, } @article {pmid40016277, year = {2025}, author = {Keykha, KA and Alinejad-Naeini, M and Peyrovi, H}, title = {The mediating role of psychological capital in the association between work engagement and occupational stress in pediatric nurses.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {7041}, pmid = {40016277}, issn = {2045-2322}, mesh = {Humans ; *Occupational Stress/psychology/epidemiology ; Female ; Male ; Adult ; *Work Engagement ; Surveys and Questionnaires ; *Nurses, Pediatric/psychology ; Middle Aged ; }, abstract = {Pediatric nurses are exposed to occupational stress due to the demanding care of sick children and complex interactions with families. The negative impact on nurse's physical and mental health, stress can also affect the quality of care. On the other hand, work engagement as a positive mental state and psychological capital as one of the supporting factors can help improve conditions and reduce occupational stress. However, the role of psychological capital in the relationship between occupational stress and work engagement in pediatric nurses needs further research. The aim of this study was to determine the mediating role of psychological capital in the relationship between work engagement and occupational stress in nurses working on pediatric wards. The present study was a predictive correlational study using the path analysis model. The statistical population of this study consisted of 251 pediatric nurses. The sampling was conducted from December 2023 to May 2024. Data collection instruments included the Demographic Profile Form, Chen's occupational Stress Questionnaire, Schaufeli et al.'s Work Engagement Questionnaire, and Luthans' Psychological Capital Questionnaire. The data analysis was carried out using the SPSS 26 and AMOS 24 software. The results of this study showed that there was an inverse and significant relationship between work engagement and occupational stress in nurses working in the pediatric ward (p < 0.001, β = -0.22). In addition, a positive and significant relationship was observed between work engagement and psychological capital among nurses (p < 0.001, β = 0.39). The results also showed that there was an inverse and significant relationship between psychological capital and occupational stress (p < 0.001, β = -0.23). The results of the final model represented psychological capital as a mediating variable that explains the relationship between work engagement and occupational stress of nurses. The results of this study showed that higher work engagement leads to a reduction in occupational stress in nurses working in the pediatric ward and that psychological capital acts as a mediating variable in this relationship. Nurses who have higher work engagement and psychological capital, experience less occupational stress. Age and work experience were also related to reduced stress and increased work engagement and psychological capital. It is suggested that hospital managers focus on educational and supportive programs to enhance psychological capital and increase the work engagement of nurses working in pediatric wards to improve the quality of care for children.}, } @article {pmid40012856, year = {2025}, author = {Minkels, C and van der Kamp, J and de Vries, R and Beek, PJ}, title = {Learning how to swim in 5- to 12-year-old children: a scoping review of evidence-based motor learning methods.}, journal = {Frontiers in sports and active living}, volume = {7}, number = {}, pages = {1505301}, pmid = {40012856}, issn = {2624-9367}, abstract = {BACKGROUND: Swimming is widely acknowledged for its safety and health benefits. Across the world children are receiving swimming lessons in which a variety of learning methods are employed. However, little is known about the effectiveness of those methods, and a comprehensive overview of pertinent research is lacking. Such an overview is needed for both researchers and instructors seeking to improve swimming skill acquisition in children.

OBJECTIVE: This scoping review aims to provide an overview of studies examining the effectiveness of motor learning methods for the acquisition of swimming skills by 5- to 12-year-old children, including an evaluation of their theoretical underpinnings, methodological quality, and core findings.

METHODS: This scoping review adhered to the PRISMA guidelines and followed Tricco et al.'s framework for conducting and reporting scoping reviews. Five bibliographic databases were systematically searched. Peer-reviewed studies in all languages published before 2025 were considered. Studies focusing on children with water-related fear were included. Gray literature, non-peer-reviewed studies and studies on specific groups (e.g., young, competitive swimmers or children with disabilities), or cognitive/motivational outcomes were excluded. Review selection and characterization were performed by three independent reviewers using pretested forms.

RESULTS: A total of 23 studies were included, which were classified into three main categories: traditional motor learning methods (n = 4), contemporary methods (n = 1), and atheoretical methods (n = 18). Traditional methods focused on video-based instruction and feedback (n = 4). Contemporary methods involved a single study on a non-linear swimming program (n = 1). Atheoretical methods were further classified into learn-to-swim programs (n = 12), learning environments (n = 3), and assistive devices (n = 3). Most studies (87%) reported a positive effect of the motor learning method under investigation during practice. However, significant methodological limitations were identified. Specifically, 87% of studies did not incorporate retention or transfer tests, 35% lacked control or comparison groups, and 48% did not provide detailed descriptions of the investigated intervention(s). Additionally, 83% of studies were not explicitly grounded in theoretical frameworks, except for the video-based studies and the study on a non-linear swimming program.

CONCLUSION: The literature on this topic is scarce, generally atheoretical and of questionable methodological quality. Addressing these shortcomings in future research will improve the evidence-base for the effectiveness of theoretically inspired learning methods for the acquisition of swimming skills in children, and their long-term retention and transfer, which in turn might result in evidence-based innovations in swimming lessons.

PRISMA (RRID:SCR_018721).}, } @article {pmid39998031, year = {2025}, author = {Burke, KM and Shea, C and Arulanandam, V and Sullivan, S and Ellrodt, AS and MacAdam, C and Carney, K and Casagrande, G and Christiansen, E and Paganoni, S}, title = {Cervical Collar Satisfaction and Functional Impact in Amyotrophic Lateral Sclerosis: A Survey Study.}, journal = {American journal of physical medicine & rehabilitation}, volume = {104}, number = {9}, pages = {809-813}, doi = {10.1097/PHM.0000000000002716}, pmid = {39998031}, issn = {1537-7385}, abstract = {OBJECTIVES: Many people with amyotrophic lateral sclerosis develop cervical muscle weakness, often managed with cervical collars. Finding supportive and comfortable collars can be challenging. This study aimed to evaluate satisfaction with various collars and their impact on activities of daily living.

DESIGN: This electronic survey study collected demographic information, clinical status, and participant experiences with commonly used cervical collars.

RESULTS: Thirty-four participants (33 with amyotrophic lateral sclerosis, 1 with primary lateral sclerosis) completed the survey, with 79% reporting neck weakness and 38% experiencing neck pain. Among those who tried cervical collars (65%), many had tried multiple options. The mean satisfaction across all collar types was 5.03 (SD = 2.92) out of 10.

CONCLUSIONS: These findings suggest current collars do not fully meet the needs of people living with amyotrophic lateral sclerosis, emphasizing the importance of improved treatment options. Future research should explore innovative technologies to improve cervical support, function, and quality of life.}, } @article {pmid39987280, year = {2025}, author = {Gellner, R and Begonia, MT and Wood, M and Rockwell, L and Geiman, T and Jung, C and Gellner, B and MacMartin, A and Manlapit, S and Rowson, S}, title = {Comparison of Instrumented Mouthguard Post-Processing Methods.}, journal = {Annals of biomedical engineering}, volume = {53}, number = {5}, pages = {1138-1147}, pmid = {39987280}, issn = {1573-9686}, mesh = {Humans ; *Mouth Protectors ; Female ; Adolescent ; *Hockey ; *Acceleration ; *Head/physiology ; }, abstract = {Instrumented head acceleration measurement devices are commonly used in research studies to determine head acceleration exposure in certain populations. Instrumented mouthguards pair directly to the user's teeth and offer six-degree-of-freedom measurements. Though many studies have recently used these devices, post-processing techniques vary by study. Other studies have attempted to label impact quality or coupling status, also with varying methods. This study sought to compare the effect of post-processing and labeling methods on reported exposure distribution characteristics in instrumented mouthguard data from ice hockey players. We collected data from 18 female adolescent ice hockey players on two teams for an entire season. We then post-processed the measured signals using five different techniques: (1) the instrumented mouthguard manufacturer's data output, (2) a 500 Hz linear acceleration filter and a 300 Hz angular velocity filter, (3) HEADSport, (4) a 100 Hz linear acceleration filter and a 175 Hz angular velocity filter, and (5) a salvaging process to detect and remove decoupling based on signal frequency content. The post-processing techniques affected the reported exposure distributions by changing the mean, median, and 95th percentile values of peak linear and angular kinematics. We also compared labeling techniques by measuring agreement and inter-rater reliability between three labeling techniques: the instrumented mouthguard manufacturer's label, Luke et al.'s coupling label, and our classification learner that detects and labels decoupling. We found that the labeling techniques had low agreement about which acceleration events were the best to keep. Labeling technique also influenced the reported distributions' descriptive statistics. Post-processing and event labeling are crucial components of head acceleration event exposure studies. Methods should be described by researchers, and standardization should be sought to allow for better cross-study comparison. Published and publicly available techniques can help move the field toward this ideal. Researchers should be aware of the potential effect post-processing can have on a population's final reported exposure metrics.}, } @article {pmid39985386, year = {2025}, author = {Peralta, LR and Marvell, CL and Barkell, J and Burns, K and Otten, C}, title = {An Ongoing Teacher Professional Development Programme to Enhance Critical Health Literacy Pedagogies and Assessment.}, journal = {Health promotion journal of Australia : official journal of Australian Association of Health Promotion Professionals}, volume = {36}, number = {2}, pages = {e70016}, pmid = {39985386}, issn = {2201-1617}, mesh = {Humans ; *Health Literacy ; Curriculum ; Australia ; Adolescent ; *School Teachers ; *Teacher Training/organization & administration ; Female ; Male ; Program Development ; }, abstract = {ISSUE ADDRESSED: Health literacy is an important asset for adolescents to develop through engagement in schooling and curriculum. The few studies that have focused on teachers, health literacy pedagogies and assessment, show that teachers find it difficult to enhance students' critical health literacy levels and to measure students' health literacy knowledge and capabilities using valid models. The aim of this study was to develop a longer-term PD programme for secondary school teachers to enhance their ability to plan for critical health literacy learning and to co-design with teachers a curricular model for assessing health literacy.

METHODS: Two face-to-face (F2F) PD sessions and two online PD sessions were scheduled with three participating specialist Health and Physical Education (HPE) teachers, seven HPE programmes were deductively analysed using Nutbeam's health literacy hierarchy and the Australian Curriculum: HPE outcomes and content.

RESULTS: Analysis showed that interactive learning activities were dominant (64%), compared with functional (4%) and critical learning activities (4%). The co-designed curriculum model for measuring student health literacy was also developed for use in Australian schools. The resultant rubric is informed by Nutbeam's model, Broder et al.'s definition and Bloom's taxonomy.

CONCLUSION: To our knowledge, this is the first ongoing teacher PD programme that has embedded co-design processes for teachers and researchers to design a curricular health literacy assessment model for Australian and international HPE programmes. SO WHAT?: The valid measurement and assessment of child and adolescent health literacy has largely been ignored in previous research. This study is the first attempt to co-design a curricular health literacy assessment for secondary schools that can be used by teachers and health professionals.}, } @article {pmid39981669, year = {2025}, author = {Falzarano, F and Greenfield, A and Osso, F and Bumbalova, K and Bloom, RF}, title = {"Diagnose & Adios": Multi-Perspective Insights on Formal Service Use in Dementia Family Caregivers.}, journal = {The Gerontologist}, volume = {65}, number = {6}, pages = {}, pmid = {39981669}, issn = {1758-5341}, support = {K99 AG073509/AG/NIA NIH HHS/United States ; R00 AG073509/AG/NIA NIH HHS/United States ; K99AG073509/AG/NIA NIH HHS/United States ; }, mesh = {Humans ; *Caregivers/psychology ; *Dementia/nursing/psychology/therapy ; Female ; Male ; Focus Groups ; Middle Aged ; Aged ; Adult ; *Home Care Services/statistics & numerical data ; Qualitative Research ; *Community Health Services/statistics & numerical data ; }, abstract = {BACKGROUND AND OBJECTIVES: Dementia family caregiving is a complex role that becomes increasingly intense and demanding over time. The utilization of home and community-based services (HCBS) can provide knowledge and skills to foster preparedness, which may protect against adverse caregiving outcomes; yet actual uptake of services remains low. The current study aims to gather multi-perspective insights underlying the disconnect between caregivers' need for-versus utilization of-HCBS using Pearlin et al.'s (1990) stress process model as a guiding theoretical framework.

RESEARCH DESIGN AND METHODS: Five focus groups of 4-8 participants each were conducted with dementia family caregivers (n = 13) and subject matter experts (n = 17). A deductive-inductive thematic approach was used for data analysis.

RESULTS: Three overarching concepts were identified: "Pathways to Preparedness'", 'Multi-Level Barriers', and 'Bridging the Gap.' Findings reflected caregivers" need for support in 4 core areas: (a) dementia-specific education/training; (b) competent mental health support; (c) financial/legal navigation, and (4) emergency readiness. Results revealed cross-dimensional barriers across individual-, provider-, and systemic-contexts impeding HCBS access and utilization. Personalized caregiving navigation and technology were deemed potential solutions to facilitate clearer clinical pathways between unmet needs and relevant services.

DISCUSSION AND IMPLICATIONS: Results underscore the complexity of the HCBS system in the United States and highlight the multidimensional barriers disrupting the pipeline connecting caregivers to HCBS. Findings can inform web-based behavioral interventions aiming to enhance family caregivers' knowledge of, access to, and utilization of formal services in community settings.}, } @article {pmid39980064, year = {2025}, author = {Downs, J}, title = {Furthering the benefits of DBT for eating disorders: a lived experience correspondence on McColl et al.}, journal = {Journal of eating disorders}, volume = {13}, number = {1}, pages = {37}, pmid = {39980064}, issn = {2050-2974}, abstract = {This Correspondence article provides a lived experience perspective on McColl et al.'s study, which examines the use of Dialectical Behaviour Therapy for individuals with eating disorders. Drawing on experiences of DBT treatment for longstanding and severe anorexia, the author critically engages with the study's findings, highlighting both the strengths and limitations of the treatment approach McColl et al. describe. While DBT has shown promise in addressing the emotional dysregulation and distress tolerance that underlie many eating disorder behaviours, the author emphasises the need for further adaptation to cater to the complexities of co-occurring physical, psychological, and neurodivergent conditions. The benefits of DBT for eating disorders are explored through personal reflections which emphasise the value and importance of skill-development, therapeutic validation, and motivation to build a "life worth living". Additional, co-produced research is required to further develop the evidence for DBT-based approaches, with particular attention needed in addressing language, stigma, cultural biases, and exclusionary research and clinical practices. Writing from a UK context, the author ends by advocating for the reinstatement of DBT within national guidelines for eating disorder treatment, highlighting its transdiagnostic relevance and potential to provide comprehensive, holistic support for those with more complex presentations.}, } @article {pmid39978961, year = {2025}, author = {Brown, T and Gustafsson, L and McKinstry, C and Robinson, L}, title = {Advancing occupational therapy scoping reviews: Recommendations to enhance quality and methodological rigour.}, journal = {Australian occupational therapy journal}, volume = {72}, number = {1}, pages = {e70003}, pmid = {39978961}, issn = {1440-1630}, mesh = {*Occupational Therapy/standards ; Humans ; Scoping Review as Topic ; *Research Design/standards ; }, abstract = {INTRODUCTION: Scoping reviews are an increasingly popular methodological approach to collate evidence and synthesise knowledge in many fields including occupational therapy. However, many are published with potential methodological weaknesses. To address this issue, nine methodological recommendations that authors could adopt to improve the quality and rigour of published scoping reviews are proposed based on the authors' opinions and the published evidence.

OVERVIEW: It is suggested that when authors are completing a scoping review, they can consider completing one or more of the following methodological guidelines: (1) refer to the Levac et al.'s (2010) scoping review recommendations, the JBI Scoping Review Protocol, and the PRISMA Extension for Scoping Reviews (PRISMA-ScR) Checklist as methodological guides; (2) include grey literature as a standard component search strategy approach; (3) include thesis and dissertations as recognised sources of evidence; (4) apply a recognised research methodology critical appraisal/quality assessment tools and scales to evidence selected for inclusion in scoping reviews; (5) assign a level of evidence (LoE) framework to the selected evidence; (6) apply a recognised qualitative knowledge syntheses approach to the data extracted; (7) report the steps taken to ensure the trustworthiness of the qualitative knowledge synthesis approach used; (8) include consumer, stakeholder and community consultation; and (9) apply a scoping review-specific critical appraisal/quality assessment tool as a quality assurance activity. The authors are not proposing that the nine recommendations are mandatory, but instead they are methodological guidelines that scoping review authors can incorporate if they choose.

Consumers and community members were not involved in the writing of the manuscript.

CONCLUSION: Adopting the suggested methodological recommendations as a regular part of completing occupational therapy-related scoping reviews will increase their quality, precision, and rigour.}, } @article {pmid39976244, year = {2025}, author = {Herrenkohl, TI}, title = {A commentary on Kim et al.'s (2025) mapping the multifaceted approaches and impacts of adverse childhood experiences: an umbrella review of meta-analyses for Journal of Child Psychology and Psychiatry's Annual Research Review.}, journal = {Journal of child psychology and psychiatry, and allied disciplines}, volume = {66}, number = {4}, pages = {606-608}, pmid = {39976244}, issn = {1469-7610}, mesh = {Humans ; *Adverse Childhood Experiences ; Child ; Systematic Reviews as Topic ; Meta-Analysis as Topic ; }, abstract = {Research on Adverse Childhood Experiences (ACEs) has progresses at a rapid pace over the last 30 years and publications now span many fields and disciplines. With a literature this vast, it is important to stake stock of what is known and where gaps in knowledge remain by reviewing and synthesizing published findings. In this commentary, I center remarks on a well-designed umbrella review conducted by Kim et al. on the impact of ACEs. Their review adds depth and precision to earlier reviews on this topic and draws attention to areas where further research is needed, including mechanisms underlying the transmission of risk and the onset of health-related outcomes associated with ACE exposure. I conclude the commentary by echoing a call by Kim and colleagues for more investment in public health prevention to reduce ACE exposure, lessen trauma symptoms, and reduce costs to society.}, } @article {pmid39972510, year = {2025}, author = {Endres-Dighe, S and Sucaldito, AD and McDowell, R and Wright, A and LoVette, A and Miller, WC and Go, V and Gottfredson O'Shea, N and Lancaster, KE}, title = {Mechanisms of resilience and coping to intersectional HIV prevention and drug-use stigma among people who inject drugs in rural Appalachian Ohio.}, journal = {Harm reduction journal}, volume = {22}, number = {1}, pages = {18}, pmid = {39972510}, issn = {1477-7517}, support = {K01 DA048174/DA/NIDA NIH HHS/United States ; UG3DA044822//National Institute of Drug Abuse/ ; K01DA048174//National Institute of Drug Abuse/ ; R36DA060059//National Institute of Drug Abuse/ ; }, mesh = {Humans ; *Social Stigma ; *HIV Infections/prevention & control/psychology ; *Resilience, Psychological ; Male ; *Adaptation, Psychological ; *Substance Abuse, Intravenous/psychology ; Female ; Rural Population ; Adult ; Social Support ; Ohio ; Middle Aged ; Appalachian Region ; }, abstract = {BACKGROUND: Intersectional stigma of drug-use and HIV hinders provision and utilization of HIV prevention services for people who inject drugs (PWID), particularly within rural US communities. Resilience and coping may be critical for PWID to counter pervasive stigma.

METHODS: Between October 2021 and July 2022, 35 in-depth interviews were conducted in Appalachian Ohio to understand the intersection of drug-use and HIV prevention stigma and how resilience and coping processes are displayed, shared, and enacted. Interviews were audio-recorded and transcribed verbatim. Thematic analysis was conducted, guided by Harper et al.'s four key resilience processes: (a) engaging in health-promoting cognitive processes, (b) enacting in health behavioral practices, (c) exchanging social support, and (d) empowering other PWID to engage in health behavior practices.

RESULTS: Resilience processes aligned with the Harper framework with additional coping processes identified, including anticipation strategies and maladaptive coping. Empowering other PWID emerged as a prominent resiliency process, often supported by systems of support like syringe service programs (SSPs), which provided resources and helped reduce stigma. However, bidirectional social support was constrained, as PWID frequently acted as providers of resources and referrals for peers despite limited knowledge of HIV prevention strategies and feeling unsupported themselves. Anticipation strategies were employed to manage anticipated stigma, including accessing support or, conversely, avoiding healthcare and refraining from disclosing drug use. Maladaptive coping included behaviors such as social isolation and self-administered medical care, highlighting critical gaps in opportunities to foster resilience.

CONCLUSIONS: Findings highlight that empowering peers and anticipation strategies can be key resilience processes, while maladaptive coping and limited bidirectional social support underscore the need for resilience-building and stigma-reduction interventions. Tailored systems of support for PWID in rural communities are critical to fostering adaptive coping and enhancing engagement with HIV prevention services.}, } @article {pmid39968231, year = {2025}, author = {Nagadi, E and Muryani, A and Adang, RAF}, title = {Integrated Endodontic and Restorative Management of C-Shaped Canals with Severe Coronal Loss in Mandibular Second Molar: A Case Report.}, journal = {Clinical, cosmetic and investigational dentistry}, volume = {17}, number = {}, pages = {121-134}, pmid = {39968231}, issn = {1179-1357}, abstract = {This case report describes the endodontic treatment of a lower right second molar with a C-shaped root canal in a 49-year-old woman exhibiting severe loss of coronal structure. Clinical examination revealed a cavity with temporary filling on tooth 47, which tested negative to cold stimuli but was positive to percussion and bite tests. Cone beam computed tomography (CBCT) scan revealed a C-shaped canal morphology with associated periapical radiolucency, graded as CBCT-PAI score 4. The canal was classified as C3 subdivision III (Melton et al), C3 type II (Fan et al), and [2]47 M[2-2]D[2-1] (Ahmed et al's). A non-surgical endodontic procedure was performed using metallurgically gold heat-treated files, passive ultrasonic irrigation, and warm hydraulic condensation obturation. Post-endodontic restoration included a post and core build-up with the wallpapering technique and a zirconia overlay. This case highlights the importance of CBCT imaging for diagnosis and treatment planning, careful selection of endodontic instruments and technique, and the use of advanced restoration methods to improve the outcome of challenging C-shaped canal treatments with extensive cavity involvement.}, } @article {pmid39967061, year = {2025}, author = {Jensen, M}, title = {Social media component effects: a commentary on Maheux et al. (2024).}, journal = {Journal of child psychology and psychiatry, and allied disciplines}, volume = {66}, number = {4}, pages = {592-594}, pmid = {39967061}, issn = {1469-7610}, mesh = {*Social Media ; Humans ; Adolescent ; *Adolescent Development/physiology ; *Adolescent Behavior ; }, abstract = {Maheux et al.s' annual review (2024) summarizes a rapidly evolving literature on the specific components (including content, features and functions) of social media that can help or hinder healthy adolescent development, highlighting how proposed effects of social media components appear to matter more for some adolescents than others. This commentary explores how conclusions of Maheux et al. (2024) can help shape future translational research on what components of social media may facilitate or undermine healthy adolescent development and who is most susceptible to these social media component effects. Future research must also address when and where social media components matter most, situating our understanding within temporal and physical context. Finally, the promise of future research is highlighted on why youth engage with social media components (motivations) and how specific components of social media exert their effects (mechanisms).}, } @article {pmid39966966, year = {2025}, author = {Downs, J}, title = {Eating disorders, dentistry, and the need for shared learning: a lived experience commentary on Gidlund et al.}, journal = {Journal of eating disorders}, volume = {13}, number = {1}, pages = {35}, pmid = {39966966}, issn = {2050-2974}, abstract = {This Commentary builds upon the findings of Gidlund et al.'s study on the oral health experiences of women in remission from eating disorders. By exploring the nuanced and deeply embodied dimensions of oral health in eating disorders, their findings also highlight the intersectional challenges faced by individuals when accessing dental care, including stigma, shame, and ambivalence about treatment. Drawing on lived experience examples and published research, this Commentary aims to add to existing evidence demonstrating the need for a more integrated, patient-centred approach to both dental and eating disorders treatment, advocating for harm-reduction strategies to prevent and minimise damage during active illness alongside more inclusive and nuanced conceptualisations of illness, treatment, and recovery. Recommendations are made to adopt non-stigmatising language, expand demographic diversity in research, and to co-produce research and treatment provision alongside people with lived experience. The bidirectional relationship between oral health and eating disorder symptoms requires the creation of greater collaboration between dentistry and ED treatment providers, where shared learning and co-produced training can improve care pathways and address systemic gaps in knowledge and treatment.}, } @article {pmid39957320, year = {2025}, author = {Lubbers-Wolterink, R and van Os-Medendorp, H and Jansen Klomp, W and Kamphorst, K}, title = {Exploring patient, informal caregiver, and nurse experiences with home-based hospital-level care for decompensated heart failure: a mixed-methods study.}, journal = {European journal of cardiovascular nursing}, volume = {24}, number = {4}, pages = {569-577}, doi = {10.1093/eurjcn/zvaf025}, pmid = {39957320}, issn = {1873-1953}, mesh = {Humans ; *Heart Failure/nursing/therapy ; *Caregivers/psychology ; Female ; Male ; Middle Aged ; Aged ; *Home Care Services, Hospital-Based ; *Patient Satisfaction ; Adult ; Surveys and Questionnaires ; Aged, 80 and over ; *Attitude of Health Personnel ; Qualitative Research ; Quality of Health Care ; }, abstract = {AIMS: Hospitals are encouraged to provide care closer to patients' homes. This study investigates how patients, informal caregivers, and nurses experience home-based hospital-level care for decompensated heart failure.

METHODS AND RESULTS: This mixed-methods study employed semi-structured interviews with 11 patients and 4 informal caregivers, a questionnaire administrated to 16 nurses from the intensive care, cardiac care, and general cardiology ward, and interviews with 4 nurses, supplemented by two group discussions.A convenience sample was utilized, member checks were performed, and two researchers analysed the patient interviews using thematic analysis based on the normalization process theory. Five overarching themes emerged: (i) Appreciation of personal environment, routines, and autonomy. (ii) Quality of care. (iii) Commitment to the treatment. (iv) Influence of personal characteristics. (v) Changing role of informal caregivers.Regarding nurse satisfaction, findings were mapped according to Proctor et al.'s implementation outcomes: acceptability: hospital-at-home care increases job satisfaction, through increased autonomy, personalized care, and patient satisfaction; appropriateness: hospital-at-home was perceived positively, although safety and adherence needed attention; adoption: hospital-at-home was not particularly challenging but offered a refreshing change; feasibility: on-call duty impacted personal commitments for some nurses; fidelity: information folders with clear protocols were deemed helpful.

CONCLUSION: Patients, caregivers, and nurses generally favour home-based heart failure treatment over hospital-based treatment. Key conditions include comprehensive education on home treatment, adherence support like dietary restriction maintenance, prioritizing patient autonomy, recognizing caregiver burden, and exploring cost-effective strategies such as collaboration with home care organizations.}, } @article {pmid39956037, year = {2025}, author = {Anis, S and Zimmerman, E and Jansen, AE and Kaya, RD and Fernandez, HH and Lopez-Lennon, C and Dibble, LE and Rosenfeldt, AB and Alberts, JL}, title = {Cognitive measures predict falls in Parkinson's disease: Insights from the CYCLE-II cohort.}, journal = {Parkinsonism & related disorders}, volume = {133}, number = {}, pages = {107328}, doi = {10.1016/j.parkreldis.2025.107328}, pmid = {39956037}, issn = {1873-5126}, mesh = {Humans ; *Accidental Falls/statistics & numerical data/prevention & control ; *Parkinson Disease/complications/physiopathology ; Male ; Female ; Aged ; Middle Aged ; *Cognitive Dysfunction/etiology/physiopathology/diagnosis ; Cohort Studies ; }, abstract = {BACKGROUND: Accurate prediction of falls in patients with Parkinson's disease (PWP) is crucial for effective prevention efforts. Historically, fall risk models have heavily relied on motor features, overlooking the vital cognitive-motor interplay essential for locomotion.

METHODS: Baseline assessments and year-long fall data from the CYClical Lower Extremity Exercise for Parkinson's disease II (CYCLE-II) trial's control group were utilized. A LASSO logistic regression model assessed thirty-seven demographic, motor, and cognitive variables to identify key fall predictors. To explore the practical implementation of predicting falls in a clinical setting, a second model was developed using a subset of nine candidate measures conducive for retrieval from electronic medical records. Models' accuracy was validated against Paul et al.'s 3-step fall prediction model.

RESULTS: Analysis included 123 participants (mean age 65.3 ± 8.3 years, 66 % males, mean disease duration 4.9 ± 4.1 years). Seventy-two participants (58.5 %) fell at least once; with 33.1 % occurring during walking, 34.4 % resulting in injuries. The initial model identified 8 predictors with an AUC of 0.68. The second model, incorporating disease duration and cognitive tests, achieved an AUC of 0.67, comparable to Paul et al.'s validation (AUC 0.66). Participants with poorer information processing and spatial memory were more prone to falling over the 12-month period.

CONCLUSIONS: Impaired cognitive performance and longer disease duration were powerful predictors in identifying a future fall in PWP. The link between cognitive performance and potential for falling reinforces the strong interplay between gait and cognition.}, } @article {pmid39955147, year = {2025}, author = {Robinson, J and Abrams, R and Price, O and Barley, E}, title = {Tools used to measure the therapeutic relationship between staff and service users in adult mental health care: A scoping review.}, journal = {Archives of psychiatric nursing}, volume = {54}, number = {}, pages = {73-83}, doi = {10.1016/j.apnu.2025.01.007}, pmid = {39955147}, issn = {1532-8228}, mesh = {Humans ; *Mental Health Services ; Adult ; *Mental Disorders/therapy ; *Professional-Patient Relations ; }, abstract = {BACKGROUND: Therapeutic relationships are key to both service user recovery and the safety of staff and service users in adult mental health care. However, staff over-involvement (crossing professional boundaries including sexual and emotional exploitation) and under-involvement (staff disinterest, avoidance or neglect) is often a cause for concern within mental health care. Little is known about measuring and assessing over / under involvement. This scoping review provides a broad understanding of existing tools used to measure this in adult mental health care.

OBJECTIVE: To explore what measures are used, and the characteristics of the identified measures, to understand the therapeutic relationship between staff and adult service users in mental health care settings.

DESIGN: Scoping review.

SETTING(S): Adult mental health settings.

PARTICIPANTS: Service users and staff.

METHODS: This review is guided by Levac et al.'s six stage methodology of scoping review frameworks. The reporting of this review has been guided by the PRISMA-ScR.

RESULTS: Of 2863 papers found, 23 were eligible for inclusion. The papers identified 14 scales. No tool specifically measured over- or under- involvement. Finally, data indicates that scales should be specific to their intended setting as the nature of therapeutic relationships may vary by setting.

CONCLUSIONS: Definitions of therapeutic relationships and over- and under-involvement relevant to different settings are needed. There is a need to develop setting-specific scales to measure therapeutic involvement and definitions for over- and under- involvement. This would enhance care provided to service users and encourage staff members to challenge their own boundary setting practices.

REGISTRATION: https://osf.io/93dxp/.}, } @article {pmid39954573, year = {2025}, author = {Kiernan, MC and Timmins, HC}, title = {Utility of the Gold Coast criteria for amyotrophic lateral sclerosis: Experience with fast progressors.}, journal = {Journal of the neurological sciences}, volume = {470}, number = {}, pages = {123417}, doi = {10.1016/j.jns.2025.123417}, pmid = {39954573}, issn = {1878-5883}, } @article {pmid39952846, year = {2025}, author = {Campbell, KM and Collazo, A and Yu, X and Walcher, C}, title = {Institutional characteristics, faculty rank and URM faculty representation.}, journal = {Journal of the National Medical Association}, volume = {117}, number = {1}, pages = {42-54}, doi = {10.1016/j.jnma.2025.01.006}, pmid = {39952846}, issn = {1943-4693}, mesh = {*Faculty, Medical/statistics & numerical data ; Humans ; *Schools, Medical/statistics & numerical data/organization & administration ; United States ; *Minority Groups/statistics & numerical data ; }, abstract = {INTRODUCTION: It has been well documented that underrepresented faculty in academic medicine are concentrated in lower faculty ranks than their well represented counterparts. This promotion disparity has resulted in concerted efforts by medical institutions to change academic culture and climate surrounding this group. This study provides a more detailed characterization of minority faculty underrepresentation, evaluating longitudinal trends in faculty rank among US medical schools looking particularly at academic rank, region, ownership, institution type, social mission score and research intensity ranking.

MATERIALS AND METHODS: Using data from the AAMC Faculty Roster, AAMC Organizational database, and Mullan et al.'s social mission score, multiple adjusted Generalized Estimating Equation (GEE) models were constructed to evaluate trends in faculty number by race/ethnicity, academic rank, and specific institutional characteristics as noted above.

RESULTS AND DISCUSSION: Compared to URM faculty in the South, the change rate of URM faculty is higher by 1.7 % in the West. At the Instructor rank, there are increased rates of change for all racial groups in the West when compared to the South by 6.3 % for Asian faculty, 5.1 % for White faculty, and 5 % for URM faculty. URM faculty at HBCUs at the Instructor level have decreased rates of change by 4.9 % as compared to predominantly white institutions. URM Professor rank faculty at private institutions showed significant increased rates of change of 1.7 % as compared to public institutions. URM faculty at the Professor rank had a decreased rate of 1.4 % at schools with high social mission score compared to low social mission scores.

IMPLICATIONS: There are differences in overall URM faculty trends based on region, ownership, institution type, social mission score and research intensity ranking. All institutional characteristics showed different effects on URM faculty at specific academic ranks and the reasons for these differences need further study to be more fully understood.}, } @article {pmid39950243, year = {2025}, author = {Shyr, C and Harris, PA}, title = {Reply to Layne et al.'s Letter to the Editor.}, journal = {Journal of the American Medical Informatics Association : JAMIA}, volume = {32}, number = {6}, pages = {1089}, pmid = {39950243}, issn = {1527-974X}, support = {K99 LM014429/LM/NLM NIH HHS/United States ; U24 TR004432/TR/NCATS NIH HHS/United States ; 1K99LM014429-01/TR/NCATS NIH HHS/United States ; 1U24TR004432-01/TR/NCATS NIH HHS/United States ; }, } @article {pmid39946651, year = {2025}, author = {Supianto, }, title = {Expanding Intersectionality: Rethinking Inclusive Sexualities Education for Queer Multi-Minority Identities.}, journal = {Journal of homosexuality}, volume = {}, number = {}, pages = {1-3}, doi = {10.1080/00918369.2024.2442652}, pmid = {39946651}, issn = {1540-3602}, abstract = {This commentary critically evaluates Decaro et al.'s study on inclusive sexualities education for queer individuals with multi-minority identities in Italy and the Netherlands. While the study highlights systemic inadequacies and advocates for intersectional frameworks, it must address broader identity dimensions and actionable reforms. This critique emphasizes methodological limitations, the need for cross-cultural parity, and alternative policy pathways, including digital education tools. By broadening the scope and proposing systemic changes, this commentary aims to advance transformative practices in inclusive sexuality education.}, } @article {pmid39946632, year = {2025}, author = {Wendt, LP}, title = {Points of contention in measure evaluation can arise from the use of divergent validity frameworks: A reply to Conway et al. (2025).}, journal = {Psychological assessment}, volume = {37}, number = {3}, pages = {133-136}, doi = {10.1037/pas0001361}, pmid = {39946632}, issn = {1939-134X}, mesh = {Humans ; Reproducibility of Results ; *Theory of Mind ; *Psychometrics/standards ; }, abstract = {This reply to Conway et al. (2025) illustrates how points of contention in the evaluation of mindreading (or theory of mind) measures can arise from the use of divergent validity concepts. The construct validity model used in Wendt et al.'s (2024) empirical study contrasts with the perspective implicit in Conway and colleagues' commentary, which is more consistent with Lennon's (1956) content validity model. This is reflected in the authors' conception of the nature of what is to be measured (i.e., the measurand), the criterion for what makes a measure superior (i.e., validity), and the proposed methods for judging this (i.e., validation). The mismatch between the validity concepts adopted by the respective authors has three major implications: First, Conway and colleagues' critique does not fully address the specific goals, assumptions, and intricacies of construct validation methodology. Second, their approach to measuring mindreading should not be confused with, or considered as an alternative to, construct validation but is valuable in its own right. Third, the two validity frameworks mentioned offer unique opportunities for different phases of the research process. While a content validity approach can be valuable for describing an empirical phenomenon that seems worthy of explanation (e.g., real-world mindreading), a construct validity approach can identify the theoretical constructs that might help explain it (e.g., mindreading ability). (PsycInfo Database Record (c) 2025 APA, all rights reserved).}, } @article {pmid39945515, year = {2025}, author = {Floyd, K and Ray, CD and Hesse, C}, title = {Theoretic principles of rational emotive behavior therapy (REBT) and loneliness: a multinational replication of Hyland et al. (2019).}, journal = {Cognitive behaviour therapy}, volume = {}, number = {}, pages = {1-19}, doi = {10.1080/16506073.2025.2465760}, pmid = {39945515}, issn = {1651-2316}, abstract = {Loneliness has detrimental effects on physical and mental well-being, making relevant any systematic means of inhibiting its impact. Whereas interventions based on cognitive behavior therapies have shown efficacy, interventions based on Ellis's rational emotive behavior therapy (REBT) have not been systematically assessed. In 2019, Hyland et al. demonstrated that the REBT theoretic principles of psychopathology and psychological health significantly predict loneliness scores, providing an empirical justification for later intervention efforts. The Hyland et al. sample was small, with limited demographic and geographic diversity. This paper replicates the Hyland et al. analyses using a larger (N = 3,064) sample drawn from the United States, United Kingdom, Canada, Australia, and South Africa. The present results replicate Hyland et al.'s results for both the psychopathology and psychological health models, with minimal variation in model fit from country to country. Implications for the development of an REBT-based intervention to treat loneliness are discussed.}, } @article {pmid39945200, year = {2025}, author = {Rovito, MJ and Martinez, S and Thomas, K and Chauhan, K and Gibson, S}, title = {Women, Men, and Cancer Survivorship: A Commentary on Current Data and Possible Underlying Issues.}, journal = {American journal of men's health}, volume = {19}, number = {1}, pages = {15579883241309039}, pmid = {39945200}, issn = {1557-9891}, mesh = {Humans ; Male ; Female ; *Cancer Survivors/statistics & numerical data ; *Neoplasms/mortality/epidemiology/diagnosis ; *Survivorship ; United States/epidemiology ; Survival Rate ; Sex Factors ; }, abstract = {Tonorezos et al.'s recent analysis of U.S. cancer survivorship prevalence provides insightful commentary on the dramatic increase of those surviving the disease over the last 50 years. This growth is reflective of improvements in cancer detection, treatment, and the effects of an aging population. While survival rates have seen a significant increase, more focus is needed on the long term and postsurvivorship health care. What Tonorezos et al.'s piece also indicates is that survivorship trends reveal disparities based on several variables, such as age, sex, and cancer type. Women tend to be diagnosed earlier and have higher survival rates when compared to men, arguably due to more frequent screenings vis-a-vis a sequela of increased utilization of care. Men have higher cancer incidence rates among the aging population, accompanied by lower survival rates, frequently linked to late diagnosis and less utilization of preventive care. Addressing sex-specific disparities is pivotal to developing future treatment plans among cancer survivors. Health care providers must adjust to the multifaceted demands of the population. Public health movements should focus on increasing awareness and promotion of early detection in the male population, taking note of the successful initiatives seen in women's health. It is imperative that these disparities and long-term needs are assimilated into the comprehensive conversation about cancer care to improve outcomes for all survivors.}, } @article {pmid39943621, year = {2025}, author = {Choi, J and Son, S and Kwon, D and Park, Y}, title = {A PUF-Based Secure Authentication and Key Agreement Scheme for the Internet of Drones.}, journal = {Sensors (Basel, Switzerland)}, volume = {25}, number = {3}, pages = {}, pmid = {39943621}, issn = {1424-8220}, support = {RS-2024-00450915//National Research Foundation of Korea/ ; }, abstract = {The Internet of Drones (IoD) is an emerging industry that offers convenient services for humans due to the high mobility and flexibility of drones. The IoD substantially enhances human life by enabling diverse drone applications across various domains. However, a malicious adversary can attempt security attacks because communication within an IoD environment is conducted through public channels and because drones are vulnerable to physical attacks. In 2023, Sharma et al. proposed a physical unclonable function (PUF)-based authentication and key agreement (AKA) scheme for the IoD. Regrettably, we discover that their scheme cannot prevent impersonation, stolen verifier, and ephemeral secret leakage (ESL) attacks. Moreover, Sharma et al.'s scheme cannot preserve user untraceability and anonymity. In this paper, we propose a secure and lightweight AKA scheme which addresses the shortcomings of Sharma et al.'s scheme. The proposed scheme has resistance against diverse security attacks, including physical capture attacks on drones, by leveraging a PUF. Furthermore, we utilize lightweight operations such as hash function and XOR operation to accommodate the computational constraints of drones. The security of the proposed scheme is rigorously verified, utilizing "Burrows-Abadi-Needham (BAN) logic", "Real-or-Random (ROR) model", "Automated Validation of Internet Security Protocols and Application (AVISPA)", and informal analysis. Additionally, we compare the security properties, computational cost, communication cost, and energy consumption of the proposed scheme with other related works to evaluate performance. As a result, we determine that our scheme is efficient and well suited for the IoD.}, } @article {pmid39943460, year = {2025}, author = {Lee, HJ and Kook, S and Kim, K and Ryu, J and Lee, Y and Won, D}, title = {LAMT: Lightweight and Anonymous Authentication Scheme for Medical Internet of Things Services.}, journal = {Sensors (Basel, Switzerland)}, volume = {25}, number = {3}, pages = {}, pmid = {39943460}, issn = {1424-8220}, support = {RS-2023-00239728//National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT)/ ; }, mesh = {*Internet of Things ; *Computer Security ; Humans ; Confidentiality ; Algorithms ; Privacy ; Internet ; }, abstract = {Medical Internet of Things (IoT) systems can be used to monitor and treat patient health conditions. Security and privacy issues in medical IoT services are more important than those in any other IoT-enabled service. Therefore, various mutual authentication and key-distribution schemes have been proposed for secure communication in medical IoT services. We analyzed Hu et al.'s scheme and found that an attacker can impersonate legitimate sensor nodes and generate illegitimate session keys using the information stored in the sensor node and the information transmitted over the public channel. To overcome these vulnerabilities, we propose a scheme that utilizes physically unclonable functions to ensure a secure session key distribution and increase the computational efficiency of resource-limited sensor nodes. In addition, the proposed scheme enhances privacy protection using pseudonyms, which we prove using a formal security analysis tool, ProVerif 2.05.}, } @article {pmid39937978, year = {2025}, author = {Montés-Micó, R and Nilsson, M and Brautaset, R and Venkataraman, AP and Domínguez-Vicent, A}, title = {Analysis of Crystalline Lens Tilt and Decentration Using a Fully Automated Swept-Source Optical Coherence Tomography Biometer.}, journal = {Journal of refractive surgery (Thorofare, N.J. : 1995)}, volume = {41}, number = {2}, pages = {e155-e163}, doi = {10.3928/1081597X-20241230-03}, pmid = {39937978}, issn = {1938-2391}, mesh = {Humans ; *Tomography, Optical Coherence/methods/instrumentation ; Prospective Studies ; *Lens, Crystalline/diagnostic imaging ; Male ; Female ; Biometry/methods ; Middle Aged ; Adult ; Axial Length, Eye ; Aged ; Reproducibility of Results ; Anterior Chamber/diagnostic imaging ; Young Adult ; Aged, 80 and over ; }, abstract = {PURPOSE: To evaluate the repeatability of a fully automated swept-source optical coherence tomography (SS-OCT) biometer to measure healthy crystalline lens decentration and tilt and their correlation with other biometric parameters.

METHODS: In this prospective study, 135 eyes of 135 patients were included. Ocular biometric parameters including crystalline decentration and tilt were measured three times with the Eyestar 900 SS-OCT (Haag-Streit AG). The repeatability was analyzed with the within-subject standard deviation (Sw), coefficient of variability, and coefficient of repeatability. Other biometric parameters such as keratometry (K1 flat and K2 steep), anterior chamber depth (ACD), lens thickness (LT), and axial length (AL) were also analyzed to explore possible relationships.

RESULTS: For K1, K2, ACD, LT, and AL, Sw values were 0.07 diopters (D), 0.14 D, 0.01 mm, 0.02 mm, and 0.01 mm, respectively. For X and Y decentration and tilt, Sw values were 0.01, 0.02, and 0.39 mm, respectively. The correlation coefficient (r) between the crystalline lens tilt was low (r < -0.300) for all ocular biometric parameters, and was only associated with the AL (P < .001, r = -0.295). The r value between the decentration along the X and Y direction and the ocular biometric parameters was in all cases lower than 0.300. There was only a correlation between the decentration (Y direction) and K2 and ACD parameters (P < .001, P = .007, respectively). The linear regression parameters resulted in a slope value lower than -0.15 between any direction of the decentration and the other ocular biometric parameters.

CONCLUSIONS: The Eyestar 900 provides repeatable measurements for crystalline lens decentration and tilt. AL was the only biometric parameter correlated with the crystalline lens tilt, and keratometry, ACD, and LT were correlated with the crystalline lens decentration along the Y direction. [J Refract Surg. 2025;41(2):e155-e163.].}, } @article {pmid39935463, year = {2025}, author = {van Genugten, CR and Thong, MSY and van Ballegooijen, W and Kleiboer, AM and Spruijt-Metz, D and Smit, AC and Sprangers, MAG and Terhorst, Y and Riper, H}, title = {Beyond the current state of just-in-time adaptive interventions in mental health: a qualitative systematic review.}, journal = {Frontiers in digital health}, volume = {7}, number = {}, pages = {1460167}, pmid = {39935463}, issn = {2673-253X}, abstract = {BACKGROUND: Just-In-Time Adaptive Interventions (JITAIs) are interventions designed to deliver timely tailored support by adjusting to changes in users' internal states and external contexts. To accomplish this, JITAIs often apply complex analytic techniques, such as machine learning or Bayesian algorithms to real- or near-time data acquired from smartphones and other sensors. Given the idiosyncratic, dynamic, and context dependent nature of mental health symptoms, JITAIs hold promise for mental health. However, the development of JITAIs is still in the early stages and is complex due to the multifactorial nature of JITAIs. Considering this complexity, Nahum-Shani et al. developed a conceptual framework for developing and testing JITAIs for health-related problems. This review evaluates the current state of JITAIs in the field of mental health including their alignment with Nahum-Shani et al.'s framework.

METHODS: Nine databases were systematically searched in August 2023. Protocol or empirical studies self-identifying their intervention as a "JITAI" targeting mental health were included in the qualitative synthesis if they were published in peer-reviewed journals and written in English.

RESULTS: Of the 1,419 records initially screened, 9 papers reporting on 5 JITAIs were included (sample size range: 5 to an expected 264). Two JITAIs were for bulimia nervosa, one for depression, one for insomnia, and one for maternal prenatal stress. Although most core components of Nahum-Shani's et al.'s framework were incorporated in the JITAIs, essential elements (e.g., adaptivity and receptivity) within the core components were missing and the core components were only partly substantiated by empirical evidence (e.g., interventions were supported, but the decision rules and points were not). Complex analytical techniques such as data from passive monitoring of individuals' states and contexts were hardly used. Regarding the current state of studies, initial findings on usability, feasibility, and effectiveness appear positive.

CONCLUSIONS: JITAIs for mental health are still in their early stages of development, with opportunities for improvement in both development and testing. For future development, it is recommended that developers utilize complex analytical techniques that can handle real-or near-time data such as machine learning, passive monitoring, and conduct further research into empirical-based decision rules and points for optimization in terms of enhanced effectiveness and user-engagement.}, } @article {pmid39934874, year = {2025}, author = {Prananto, K and Cahyadi, S and Lubis, FY and Hinduan, ZR}, title = {Perceived teacher support and student engagement among higher education students - a systematic literature review.}, journal = {BMC psychology}, volume = {13}, number = {1}, pages = {112}, pmid = {39934874}, issn = {2050-7283}, mesh = {Humans ; *Students/psychology ; *Motivation ; *Social Support ; *School Teachers/psychology ; *Academic Success ; Self Efficacy ; Universities ; }, abstract = {BACKGROUND: Research on student engagement has garnered significant interest from educators and practitioners because of its direct impact on academic success and achievement. Engaged students tend to perform better academically and exhibit fewer undesirable study behaviors, thereby enhancing academic outcomes.

OBJECTIVE: This systematic literature review consolidates research on the impact of perceived teacher support on student engagement in higher education. This study emphasizes the association between teacher support in improving students' academic performance, motivation, and retention. Furthermore, the review explores key theoretical frameworks, such as self-determination theory and social cognitive theory, alongside methodological tools such as measurement instruments and statistical analyses. The goal is to equip psychologists and educational researchers with insights into the relevant frameworks, tools, and methods for advancing future studies within the context of higher education.

METHODS: This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology. We conducted a comprehensive search for academic studies published in English within databases such as APA PsycNet, Scopus, ERIC, EBSCOHost, ProQuest, and PubMed to identify eligible studies published between 2014 and 2024.

RESULTS: A review of 13 selected articles revealed that both students' personal characteristics and school environment factors mediate and moderate the relationship between perceived teacher support and student engagement. The students' personal characteristics factors include self-efficacy, the fulfillment of psychological needs, and motivation, whereas school environment factors involve the learning environment and the quality of teacher-student and peer relationships. Our findings show a lack of studies prior to 2020, with most research conducted in China and limited contributions from Malaysia and Vietnam. The reviewed articles predominantly used cross-sectional quantitative designs and self-report questionnaires, employing statistical methods like path analysis and structural equation modeling. Theoretical frameworks on student engagement mostly followed Fredricks et al.'s model, while teacher support theories varied, with three main patterns identified: direct influence, mediation through basic psychological needs, and social cognitive perspectives. This review emphasizes the crucial role of teacher support in enhancing student engagement in higher education and urges further exploration in this under-researched area.

CONCLUSION: In conclusion, this review underscores the significant role of teacher support in enhancing student engagement in higher education. It highlights key theoretical frameworks and research methodologies, offering valuable insights for future studies aimed at advancing teacher support and student engagement in this context.}, } @article {pmid39930076, year = {2025}, author = {Kalantari, F and Faez, K and Amindavar, H and Nazari, S}, title = {Improved image reconstruction from brain activity through automatic image captioning.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {4907}, pmid = {39930076}, issn = {2045-2322}, mesh = {Humans ; *Brain/diagnostic imaging/physiology ; *Magnetic Resonance Imaging/methods ; *Image Processing, Computer-Assisted/methods ; *Brain Mapping/methods ; Semantics ; Algorithms ; Neural Networks, Computer ; }, abstract = {Significant progress has been made in the field of image reconstruction using functional magnetic resonance imaging (fMRI). Certain investigations reconstructed images with visual information decoded from brain signals, yielding insufficient accuracy and quality. The combination of semantic information in the reconstruction was recommended to improve performance. However, this issue continues to come across numerous difficulties. To address such problems, we proposed an approach that combines semantically complex details with visual details for reconstruction. Our proposed method consists of two main modules: visual reconstruction and semantic reconstruction. In the visual reconstruction module, visual information is decoded from brain data using a decoder. This module employs a deep generator network (DGN) to produce images and utilizes a VGG19 network to extract visual features from the generated images. Image optimization is performed iteratively to minimize the error between features decoded from brain data and features extracted from the generated image. In the semantic reconstruction module, two models BLIP and LDM are employed. Using the BLIP model, we generate 10 captions for each training image. The semantic features extracted from the image captions, along with brain data obtained from training sessions, are used to train a decoder. The trained decoder is then utilized to decode semantic features from human brain activity. Finally, the reconstructed image from the visual reconstruction module is used as input to the LDM model, while the semantic features decoded from brain activity are provided as conditional input for semantic reconstruction. Including decoded semantic features improves reconstruction quality, as confirmed by our ablation study. Our strategy is superior both qualitatively and quantitatively to Shen et al.'s method, which utilizes a similar dataset. Our methodology achieved an accuracy of 0.812 and 0.815 for the inception and contrastive language-image pre-training (CLIP) metrics, respectively, which are excellent for the quantitative evaluation of semantic content. We achieved an accuracy of 0.328 in the structural similarity index measure (SSIM), indicating superior performance as a low-level metric. Moreover, our proposed approach for semantic reconstruction of artificial shapes and imagined images achieved acceptable success, attaining accuracies of 0.566 and 0.627 based on the CLIP metric, and 0.671 and 0.565 based on the SSIM metric, respectively.}, } @article {pmid39924724, year = {2025}, author = {Chen, LH and Wei, LC}, title = {Addressing the Unique Challenges of Paediatric Mental Health Emergency Care: Response to Bourke et al.'s Study on Young Children's Emergency Department Presentations.}, journal = {Journal of paediatrics and child health}, volume = {61}, number = {4}, pages = {653-654}, doi = {10.1111/jpc.70004}, pmid = {39924724}, issn = {1440-1754}, } @article {pmid39924695, year = {2025}, author = {Liu, S and Geng, D}, title = {White-Matter Structural Connectivity and Alzheimer's Disease: A Mendelian Randomization Study.}, journal = {Brain and behavior}, volume = {15}, number = {2}, pages = {e70286}, pmid = {39924695}, issn = {2162-3279}, support = {82372048//National Natural Science Foundation of China/ ; 22TS1400900//Science and Technology Commission of Shanghai Municipality/ ; 22ZR1409500//Science and Technology Commission of Shanghai Municipality/ ; 23S31904100//Science and Technology Commission of Shanghai Municipality/ ; 24SF1904200//Science and Technology Commission of Shanghai Municipality/ ; 24SF1904201//Science and Technology Commission of Shanghai Municipality/ ; }, mesh = {Humans ; *Alzheimer Disease/genetics/pathology/diagnostic imaging ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Magnetic Resonance Imaging ; Mendelian Randomization Analysis/methods ; Neural Pathways/pathology ; *White Matter/diagnostic imaging/pathology ; }, abstract = {BACKGROUND: Alzheimer's disease (AD) and white-matter structural connectivity have been linked in some observational studies, although it is unknown if this is a causal relationship. The purpose of this study was to examine the impact of various white-matter structural connectivity on AD via a two-sample multivariate Mendelian randomization (MR) approach.

METHODS: The genome-wide association study (GWAS) of Wainberg et al. provided the summary data on white-matter structural connectivity, and Bellenguez et al.'s study provided the GWAS aggregated data for AD. MR methods included inverse variance weighted, Mendelian randomization Egger, simple mode, weighted median, and weighted mode. Heterogeneity, horizontal pleiotropy, and "leave-one-out" analysis guaranteed the robustness of causation. Finally, reverse MR analysis was conducted on the white-matter structural connectivity that showed positive results in the forward MR analysis.

RESULTS: Among 206 white-matter structural connections, we identified 10 connections were strongly correlated with genetic susceptibility to AD. Right-hemisphere limbic network to thalamus white-matter structural connectivity and Right-hemisphere salience_ventral attention network to accumbens white-matter structural connectivity were positively correlated with the likelihood of AD, while the remaining 8 white-matter structural connections were negatively related with AD. None of the above 10 white-matter structural connections have a reverse causal relationship with AD.

CONCLUSION: Our MR study reveals a certain degree of association between white-matter structural connectivity and AD, which may provide support for future diagnosis and treatment of AD.}, } @article {pmid39923277, year = {2025}, author = {Hall, S and Koslouski, JB and Richter, CG and Chafouleas, SM}, title = {Measures of emotional well-being for individuals with intellectual disabilities: A scoping review of reviews.}, journal = {Research in developmental disabilities}, volume = {158}, number = {}, pages = {104940}, pmid = {39923277}, issn = {1873-3379}, support = {U24 AT011281/AT/NCCIH NIH HHS/United States ; }, mesh = {Humans ; *Intellectual Disability/psychology ; *Quality of Life/psychology ; *Emotions ; }, abstract = {OBJECTIVE: This scoping review of reviews examines how one facet of quality of life, emotional well-being (EWB), has been assessed for individuals with intellectual disabilities (ID), including the characteristics of measures that have been designed, adapted, or administered to individuals in this population.

METHODS: Following established practices for scoping reviews, we searched the ERIC, APA Psych Info, and Academic Search Premier databases in November 2022 for review articles that included measures of EWB that had been designed, adapted, or administered to individuals with ID. Following PRISMA guidelines, we conducted independent double coding at the title and abstract and full text review stages. From each included review article, we extracted the review's purpose, EWB-related construct of interest, and EWB-related measure names and authors. We then located each measure and coded its items using Park et al.'s (2023) definition of EWB. We also coded the "non-EWB" domains assessed by these measures. We used the PRISMA Extension for Scoping Reviews (PRISMA-Scr) checklist to structure our manuscript.

RESULTS: The scoping review identified 10 review articles that included 14 unique measures of EWB. Each of these measures included at least 1 item (M = 2.8) that assessed EWB. Quality of life was the most common EWB-related construct specified by review articles. Measures frequently assessed additional constructs beyond EWB, including self-determination, interpersonal relations, physical well-being, and material well-being.

CONCLUSIONS: In measures designed or adapted for individuals with ID, EWB is often included as a subcomponent of quality of life. Because of EWB's link to positive social, emotional, behavioral, and health outcomes, research is needed to identify the most salient components of EWB for individuals with ID. This would allow for measures and interventions to be developed to promote EWB in this population.

WHAT THIS PAPER ADDS: This study provides a scoping review of available measures of EWB that have been designed, adapted, or administered to individuals with ID. Study findings detail the characteristics of these measures, highlighting gaps in available EWB measures for children and adolescents with ID. We also found that emotional well-being is frequently assessed as a component of a broader construct (e.g., quality of life) using a small number of items. This suggests a need and opportunity for growth in further understanding emotional well-being assessment in individuals with ID.}, } @article {pmid39915896, year = {2025}, author = {Wassef, K and Ma, K and Durieux, BN and Brown, TL and Paladino, J and Thorne, S and Sanders, JJ}, title = {Measuring the quality of patient-provider relationships in serious illness: A scoping review.}, journal = {Palliative medicine}, volume = {39}, number = {3}, pages = {332-345}, pmid = {39915896}, issn = {1477-030X}, mesh = {Humans ; *Critical Illness/psychology ; *Professional-Patient Relations ; Male ; Female ; *Quality of Health Care/standards ; *Physician-Patient Relations ; Middle Aged ; }, abstract = {BACKGROUND: People affected by serious illness face several threats to their well-being: physical symptoms, psychological distress, disrupted social relations, and spiritual/existential crises. Relationships with clinicians provide a form of structured support that promotes shared decision-making and adaptive stress coping. Measuring relationship quality may improve quality assessment and patient care outcomes. However, researchers and those promoting quality improvement lack clear guidance on measuring this.

AIM: To identify and assess items from valid measures of patient-provider relationship quality in serious illness settings for guiding quality assessment.

DESIGN: Scoping review.

DATA SOURCES: We identified peer-reviewed, English-language articles published from 1990 to 2023 in CINAHL, Embase, and PubMed. Eligible articles described the validation of measures assessing healthcare experiences of patient populations characterized by serious illness. We used Clarke et al.'s theory of relationship quality to assess relationship-focused items.

RESULTS: From 3868 screened articles, we identified 101 publications describing 47 valid measures used in serious illness settings. Measures assessed patients and other caregivers. We determined that 597 of 2238 items (26.7%) related to relationships. Most measures (n = 46) included items related to engaging the patient as a whole person. Measures evaluated how providers promote information exchange (n = 35), foster therapeutic alliance (n = 35), recognize and respond to emotion (n = 27), and include patients in care-related decisions (n = 23). Few instruments (n = 9) assessed patient self-management and navigation.

CONCLUSIONS: Measures include items that assess patient-provider relationship quality in serious illness settings. Researchers may consider these for evaluating and improving relationship quality, a patient-centered care and research outcome.}, } @article {pmid39912530, year = {2025}, author = {Chen, CL and Wei, LC}, title = {Enhancing support for nurses' moral competence: A commentary on Wiisak et al.'s multilevel framework.}, journal = {International nursing review}, volume = {72}, number = {1}, pages = {e70003}, doi = {10.1111/inr.70003}, pmid = {39912530}, issn = {1466-7657}, } @article {pmid39904709, year = {2025}, author = {Vahey, N and Nicholson, E and Barnes-Holmes, D}, title = {A decade on: Reflecting on the limitations of the first meta-analysis of the Implicit Relational Assessment Procedure's (IRAP) criterion validity in the clinical domain.}, journal = {Journal of behavior therapy and experimental psychiatry}, volume = {87}, number = {}, pages = {102016}, doi = {10.1016/j.jbtep.2024.102016}, pmid = {39904709}, issn = {1873-7943}, mesh = {Humans ; *Meta-Analysis as Topic ; Reproducibility of Results ; }, abstract = {Hussey (in press) recently conducted a detailed critical reanalysis of Vahey, Nicholson and Barnes-Holmes' (2015) meta-analysis. Its stated purpose was to (a) examine the extent to which Vahey et al.'s (2015) meta-analysis contains errors; and (b) to test how computationally reproducible it is by current standards of best practice. Hussey identified a small number of minor numerical errors, but crucially was unable to exactly replicate the original meta-effect of r‾ = .45. Six different variations of the meta-analysis reported by Vahey et al. were used and obtained meta-effects that deviated from the original by Δr‾ = .01-.02. Hussey also reported corresponding 95% credibility intervals that were all of zero width. These discrepancies prompted the present authors to conduct a detailed audit of the original meta-analysis. This revealed one minor transposing error in addition to three identified by Hussey. Once corrected this resulted in a marginally increased Hunter and Schmidt meta-analytic effect of r‾ = .46 without a credibility interval, and a Hedges-Vevea meta-effect of r‾ = .47 with 95% confidence interval (.40, .54). This correction was too small to have any bearing on Vahey et al.'s supplementary analyses regarding publication bias or statistical power. Vahey et al. contained a much lower proportion of transposing errors than is typical of meta-analyses even still (cf. Kadlec, Sainani, & Nimphius, 2023; Lakens et al., 2016; Lakens et al., 2017). Nonetheless, Hussey highlighted important ambiguities about the theoretical and practical meaning of the meta-effect reported by Vahey et al. We clarify our position on these matters in summary, and in so doing explain why we believe that the wider IRAP literature would undoubtedly benefit from increased adoption of contemporary open science standards.}, } @article {pmid39901261, year = {2025}, author = {Ghaznavi, A and Nosratpour, M and Moteshakereh, SM and Parvandi, A and Amiri, S}, title = {Reconstructive surgery to preserve ankle function in a 5-year-old girl with bilobed distal tibia in an unclassified case of tibial hemimelia: a case report.}, journal = {Journal of medical case reports}, volume = {19}, number = {1}, pages = {46}, pmid = {39901261}, issn = {1752-1947}, mesh = {Humans ; Female ; *Tibia/abnormalities/surgery/diagnostic imaging ; Child, Preschool ; *Ectromelia/surgery/diagnostic imaging ; *Plastic Surgery Procedures/methods ; *Ankle Joint/surgery/physiopathology ; Treatment Outcome ; *Ankle/surgery/physiopathology ; }, abstract = {BACKGROUND: Tibial hemimelia is an uncommon congenital abnormality ranging from a solitary skeletal deformity to associations with other syndromes. Despite Paley et al.'s detailed classification of tibial hemimelia, some unique sporadic cases still do not fit within this system. In 2021, Chong et al. proposed the most recent surgical approach based on the Paley classification, which inspired cases such as ours.

CASE PRESENTATION: This case study presents a novel case of tibial hemimelia characterized by a bilobed distal tibia, a shortened first ray, and an equinovarus deformity in a 5-year-old Iranian (Lur) girl. She experienced pain, limping, and cosmetic concerns. The surgical procedures performed for preservation are thoroughly described and discussed.

CONCLUSION: This case has been identified as a new variant of Paley type 2. A staged approach to reconstructive surgery was advocated to ensure the preservation of ankle function and to prevent extreme procedures such as amputation. The most recent follow-up demonstrated promising results.}, } @article {pmid39901141, year = {2025}, author = {O'Connor, H and Meloncelli, N and Wilkinson, SA and Scott, AM and Vincze, L and Rushton, A and Dawson, S and Hollis, J and Whiteoak, B and Gauci, S and de Jersey, S}, title = {Effective dietary interventions during pregnancy: a systematic review and meta-analysis of behavior change techniques to promote healthy eating.}, journal = {BMC pregnancy and childbirth}, volume = {25}, number = {1}, pages = {112}, pmid = {39901141}, issn = {1471-2393}, mesh = {Humans ; Female ; Pregnancy ; *Diet, Healthy/methods ; *Behavior Therapy/methods ; Randomized Controlled Trials as Topic ; *Prenatal Care/methods ; *Health Promotion/methods ; Feeding Behavior ; }, abstract = {Improving dietary intake during pregnancy can mitigate adverse consequences for women and their children. The effective techniques and features for supporting and sustaining dietary change during pregnancy and postpartum are minimally reported. The primary aims of this systematic review and meta-analysis were to summarise the effectiveness of dietary interventions for pregnant woman, identify which behaviour change techniques (BCTs) and intervention features were most frequently used and determine which were most effective at improving dietary intake. Six databases were searched to identify randomised control trials (RCTs) reporting on dietary intake in pregnant women over the age of sixteen, with an active intervention group compared to a control group receiving usual care or less intensive interventions. The Cochrane Risk of Bias Tool 1 was used to assess study validity. BCTs were coded by two authors using Michie et al.'s BCT taxonomy V1. A random effect model assessed intervention effects on indices of dietary quality and food groups (fruit, vegetables, grains and cereals, meat, and dairy) in relation to the use of BCTs and intervention features. Thirty- seven RCTs met the inclusion criteria. High heterogeneity was observed across intervention characteristics and measures of fidelity. Only half of the available BCTs were used, with eleven used once. The BCT category Reward and threat was successful in improving dietary quality and vegetable intake, whilst 'Action planning' (1.4) from the category Goals and planning significantly improved dietary quality. Interventions delivered by a nutrition professional and those that included group sessions improved dietary quality more than those delivered by other health professionals, research staff, or application-delivered interventions and delivered via other modalities. Future dietary interventions during pregnancy should incorporate and report on BCTs used in the intervention. Successful design elements for improving antenatal dietary intake may include multimodal interventions delivered by nutrition professionals and the use of Rewards and Goal setting.}, } @article {pmid39898689, year = {2025}, author = {Farrell, S and Mills, TA and Lavender, DT}, title = {Exploring parental knowledge, care-seeking, and support strategies for neonatal illness: an integrative review of the African Great Lakes region.}, journal = {Global health action}, volume = {18}, number = {1}, pages = {2450137}, pmid = {39898689}, issn = {1654-9880}, support = {/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Humans ; *Health Knowledge, Attitudes, Practice ; *Parents/psychology ; Infant, Newborn ; *Patient Acceptance of Health Care ; Africa South of the Sahara ; *Infant, Newborn, Diseases/therapy ; Female ; Socioeconomic Factors ; }, abstract = {BACKGROUND: Sub-Saharan Africa shoulders much of the global burden of neonatal mortality. Quality postnatal care is often lacking due to availability, accessibility, mistrust of health systems, and socio-economic barriers, yet delays in care-seeking contribute to avoidable neonatal deaths. Research highlights the urgent need for improved health education about neonatal illness; however, contextual factors are rarely considered, and few interventions have been implemented.

OBJECTIVES: To critically examine the literature on parents' knowledge of neonatal illness and care-seeking behaviour and evaluate interventions supporting parental understanding in sub-Saharan African Great Lakes countries.

METHODS: Systematic searches were conducted in CINAHL, MEDLINE, Global Health, the Cochrane Library, and thesis repositories. Studies meeting inclusion criteria were critically analysed using Whittemore and Knafl's framework, and quality was assessed with Hawker et al.'s tool, following PRISMA guidelines.

RESULTS: Seventy studies (48 quantitative, 14 qualitative, eight mixed methods) were reviewed. The first theme, "poor knowledge of neonatal illness", showed parents struggled to recognise illness, with knowledge affected by maternity and socio-economic factors. The second theme, "sub-optimal healthcare-seeking behaviour", highlighted delayed care-seeking due to cultural, social, and economic factors. Finally, "strategies to support parents' understanding" emphasised the roles of community workers, health education phone calls, SMS, and videos, and neonatal monitoring systems.

CONCLUSIONS: Parental knowledge of neonatal illness is generally low, and care-seeking is influenced by beliefs, trust in healthcare, and logistical challenges. While community health workers and multi-media interventions appear effective, health education efforts must address contextual barriers and beliefs to improve recognition and care-seeking for neonatal illness.}, } @article {pmid39887681, year = {2025}, author = {Frenzel, AC and Kleen, H and Marx, AKG and Sachs, DF and Baier-Mosch, F and Kunter, M}, title = {Is it in their words? Teachers' enthusiasm and their natural language in class-A sentiment analysis approach.}, journal = {The British journal of educational psychology}, volume = {}, number = {}, pages = {}, doi = {10.1111/bjep.12734}, pmid = {39887681}, issn = {2044-8279}, support = {(FR 2642/8-1)//Deutsche Forschungsgemeinschaft/ ; }, abstract = {INTRODUCTION: Teacher enthusiasm is an undisputedly important characteristic of teachers, with demonstrated positive effects on student outcomes. Existing research typically operationalised teacher enthusiasm via trait-based teacher- or student ratings. Strikingly little is known about how teachers' trait enthusiasm manifests in their actual in-situ classroom behaviour. Some findings have been reported regarding teachers' nonverbal behaviours, but the links between teacher enthusiasm and teacher language are unknown so far.

METHODS: The present contribution fills this research gap by applying lexicon-based sentiment analysis to quantify teachers' emotional tone from transcribed teacher utterances obtained from video recordings of full mathematics lessons (45 min). N = 19 secondary school mathematics teachers and their N = 393 students participated in our study. We realised the sentiment analysis using Remus et al.'s emotion lexicon SentiWS (v2.0, 2019). We obtained both teacher self-reports and student ratings to assess teachers' enthusiasm, shown habitually (trait), and during the videotaped lesson (in situ).

RESULTS: Regarding trait enthusiasm, teachers' own, but not the students', ratings were positively linked with teachers' verbally expressed sentiment in the videotaped lesson, specifically its positive valence. Regarding in-situ enthusiasm, associations were even larger but also did not reach significance for the student ratings.

CONCLUSION: This is the first study to employ sentiment analysis on transcripts of German teachers' in-class talk. Besides the quantitative links between teacher enthusiasm and their language, it also provides qualitative insights on positive emotional teacher talk in mathematics.}, } @article {pmid39886812, year = {2025}, author = {De Troij, J and Bervoets, C}, title = {Points regarding neuroscience-based nomenclature: evaluating its impact on psychiatric residency training.}, journal = {International clinical psychopharmacology}, volume = {40}, number = {2}, pages = {119-122}, doi = {10.1097/YIC.0000000000000561}, pmid = {39886812}, issn = {1473-5857}, mesh = {Humans ; *Internship and Residency/methods ; *Terminology as Topic ; *Psychiatry/education ; *Neurosciences/education ; Belgium ; Male ; Female ; Longitudinal Studies ; Focus Groups ; Adult ; Surveys and Questionnaires ; }, abstract = {This study evaluates the impact of neuroscience-based nomenclature (NbN) training on psychiatric residents in Flanders, Belgium. Addressing Zemach et al.'s findings on NbN's potential, we investigated its application in clinical practice. We assessed changes in knowledge, prescribing habits, and communication skills through focus groups and a longitudinal survey. Our results indicated no statistically significant shifts post-training, highlighting the complexity of integrating NbN into clinical practice. These findings underscore the critical need for psychopharmacological nomenclature and psychopathology to evolve in tandem, ensuring that advancements in understanding mental disorders align with pharmacological education.}, } @article {pmid39886649, year = {2024}, author = {AlJoghaiman, E}, title = {The Relationship Between Mental Health and Periodontal Disease: Insights from NHANES Data.}, journal = {F1000Research}, volume = {13}, number = {}, pages = {709}, pmid = {39886649}, issn = {2046-1402}, mesh = {Humans ; Female ; Male ; Middle Aged ; Nutrition Surveys ; *Periodontal Diseases/epidemiology/psychology ; *Mental Health ; Adult ; Aged ; United States/epidemiology ; Prevalence ; }, abstract = {INTRODUCTION AND AIM: Periodontal disease, initiated by dental biofilm and influenced by various local and systemic factors, includes stress as a potential contributor to its progression. Despite associations with severe forms like acute necrotizing ulcerative gingivitis, a comprehensive large-sample study linking stress to periodontal disease is lacking. This study aims to investigate the relationship between mental health and periodontal disease.

MATERIALS AND METHODS: Leveraging data (secondary dataset) from the National Health and Nutrition Examination Survey (NHANES) from 2011-2012 and NHANES 2013-2014 cycles, relevant information was extracted. Mental health was the exposure variable, and periodontal disease, assessed through indices following Eke et al.'s definition, served as the outcome. Covariates (demographical characteristics) impacting periodontal disease were considered, and disease status analyses employed the Rao-Scott chi-squared test. A logistic regression model assessed mental health's impact on periodontal disease.

RESULTS: Among the 2764 Participants, more than a quarter (29.1%) were aged over 60 years, 52% were females. Logistic regression indicated higher odds of periodontal disease among individuals feeling bad about themselves for more than half of the day (OR 1.170, 95% CI 0.533-2.474), though statistical significance was not reached. Periodontitis prevalence significantly varied based on marital status, with 6.6% of married and 10.8% of unmarried Participants affected. Notably, a statistically significant difference in periodontitis prevalence existed between Participants with health insurance (8.3%) and those without (16.5%).

CONCLUSION: Our findings suggest trends in periodontal disease prevalence linked to mental health, marital status, and access to health insurance. However, the absence of statistically significant findings calls for caution in interpreting these relationships. We recommend that future studies further investigate these potential associations to provide a clearer understanding.}, } @article {pmid39885294, year = {2025}, author = {Enichen, EJ and Heydari, K and Li, B and Kvedar, JC}, title = {Telemedicine expands cardiovascular care in China - lessons for health equity in the United States.}, journal = {NPJ digital medicine}, volume = {8}, number = {1}, pages = {71}, pmid = {39885294}, issn = {2398-6352}, abstract = {Liu et al.’s recent study reveals that telemedicine expanded access to cardiovascular care in China, enabling patients in poorer areas of the country to access care in cities with more resources. While these findings may support the global expansion of telemedicine, implementation often proves challenging. This article examines the potential and limitations of adopting similar telemedicine efforts within the U.S. to advance geographic health equity.}, } @article {pmid39881246, year = {2025}, author = {Tajalli, S and Parvizy, S and Ebadi, A and Zamaniashtiani, F and Kenner, C}, title = {Understanding the experience of the mothers' ability to take care of their preterm infants related to in-hospital and post-discharge: a qualitative content analysis.}, journal = {BMC pediatrics}, volume = {25}, number = {1}, pages = {72}, pmid = {39881246}, issn = {1471-2431}, mesh = {Humans ; *Infant, Premature ; Female ; Infant, Newborn ; *Mothers/psychology ; Adult ; Qualitative Research ; Patient Discharge ; Iran ; Male ; Middle Aged ; Intensive Care Units, Neonatal ; Mother-Child Relations ; *Infant Care/psychology ; Interviews as Topic ; }, abstract = {BACKGROUND: Preterm infants may experience many health and developmental issues, which continue even after discharge from the neonatal intensive care unit. Once home, the mother, as a non-professional and the primary caregiver will be responsible for the essential care of her preterm infant.

PURPOSE: Understanding the take care ability in mothers with preterm infants.

METHODS: The content analysis method was used. The data were collected using in-depth and semi-structured interviews from April 2021 to February 2022. Eleven mothers, two fathers, two grandmothers, one neonatal nurse, and two neonatologists with a mean age of 36.05 ± 10.88 years were selected using purposeful and snowballing sampling in Tehran, Iran. Allocating adequate time for data collection, gathering data through different methods, peer checking by two qualitative researchers, long interaction with the settings, maximum variation sampling, appropriate quotations, and showing the range of facts fairly and honestly were considered to ensure the trustworthiness of this study. The data were analyzed through Lindgren et al.'s approach using MAXQDA software.

RESULTS: Based on the findings and participants' experiences in 18 deep interviews, the mothers with desirable care ability have adequate ability as described by 17 subcategories and are categorized into five dimensions. The care ability of the mothers of preterm infants upon neonatal intensive care unit discharge consisted of five categories including maternal identity, infant's needs, cognitive ability, technical ability, and psychological ability.

In the mothers of preterm infants, maternal identity and the infant's needs are antecedents of the care ability concept. The care ability of the mothers with preterm infants is distinct from those of other caregivers. This is a multi-dimensional concept and trait related to maternal cognitive ability, technical ability, and maternal psychological ability. Professional neonatal nurses should assess their care ability from multiple perspectives: cognitive, technical, and psychological abilities. They should be considered in designing empowerment and engagement programs for the improvement of the care ability of the mothers of preterm infants. Both mothers and professional neonatal nurses should take responsibility for improving the mothers' ability to take care of their preterm infants.}, } @article {pmid39866725, year = {2024}, author = {Kohnert, E and Kreutz, C}, title = {Computational Study Protocol: Leveraging Synthetic Data to Validate a Benchmark Study for Differential Abundance Tests for 16S Microbiome Sequencing Data.}, journal = {F1000Research}, volume = {13}, number = {}, pages = {1180}, pmid = {39866725}, issn = {2046-1402}, mesh = {*Benchmarking ; *RNA, Ribosomal, 16S/genetics ; Humans ; *Microbiota/genetics ; *Computational Biology/methods ; }, abstract = {BACKGROUND: Synthetic data's utility in benchmark studies depends on its ability to closely mimic real-world conditions and reproduce results obtained from experimental data. Building on Nearing et al.'s study (1), who assessed 14 differential abundance tests using 38 experimental 16S rRNA datasets in a case-control design, we are generating synthetic datasets that mimic the experimental data to verify their findings. We will employ statistical tests to rigorously assess the similarity between synthetic and experimental data and to validate the conclusions on the performance of these tests drawn by Nearing et al. (1). This protocol adheres to the SPIRIT guidelines, demonstrating how established reporting frameworks can support robust, transparent, and unbiased study planning.

METHODS: We replicate Nearing et al.'s (1) methodology, incorporating synthetic data simulated using two distinct tools, mirroring the 38 experimental datasets. Equivalence tests will be conducted on a non-redundant subset of 46 data characteristics comparing synthetic and experimental data, complemented by principal component analysis for overall similarity assessment. The 14 differential abundance tests will be applied to synthetic and experimental datasets, evaluating the consistency of significant feature identification and the number of significant features per tool. Correlation analysis and multiple regression will explore how differences between synthetic and experimental data characteristics may affect the results.

CONCLUSIONS: Synthetic data enables the validation of findings through controlled experiments. We assess how well synthetic data replicates experimental data, try to validate previous findings with the most recent versions of the DA methods and delineate the strengths and limitations of synthetic data in benchmark studies. Moreover, to our knowledge this is the first computational benchmark study to systematically incorporate synthetic data for validating differential abundance methods while strictly adhering to a pre-specified study protocol following SPIRIT guidelines, contributing to transparency, reproducibility, and unbiased research.}, } @article {pmid39865390, year = {2025}, author = {Cheng, SW and Wei, LC}, title = {Addressing Improper Medicine Storage Practices: Commentary on Louhisalmi et al.'s Study.}, journal = {Basic & clinical pharmacology & toxicology}, volume = {136}, number = {2}, pages = {e70005}, doi = {10.1111/bcpt.70005}, pmid = {39865390}, issn = {1742-7843}, } @article {pmid39864718, year = {2025}, author = {Boyle, LD and Marty, B and Haugarvoll, K and Steihaug, OM and Patrascu, M and Husebo, BS}, title = {Selecting a smartwatch for trials involving older adults with neurodegenerative diseases: A researcher's framework to avoid hidden pitfalls.}, journal = {Journal of biomedical informatics}, volume = {162}, number = {}, pages = {104781}, doi = {10.1016/j.jbi.2025.104781}, pmid = {39864718}, issn = {1532-0480}, mesh = {Humans ; *Neurodegenerative Diseases/therapy ; Aged ; *Clinical Trials as Topic ; Female ; Male ; *Wearable Electronic Devices ; Aged, 80 and over ; }, abstract = {BACKGROUND: Increased prevalence of neurodegenerative diseases complicates care needs for older adults. Sensing technologies, such as smartwatches, are one available solution which can help address the challenges of aging. Knowledge of the possibilities and pitfalls of these sensing technologies is of key importance to researchers when choosing a device for a trial and considering the sustainability of these technologies in real-world settings.

OBJECTIVE: This study aims to uncover hidden truths related to the suitability of smartwatches for use in clinical trials which include older adults with neurodegenerative diseases, including end-of-life and palliative care studies.

METHOD: We perform an analysis of smartwatch features vs. user and researcher needs and provide an overview of hidden expenses which should be considered by the research team. Investigative research on 11 smartwatches is presented, selected based on previous use in clinical studies and recommendations from fellow researchers.

RESULTS: We found that expenses, battery life, choice of research vs. commercial grade devices, data management, study methodology, and participant demographics are principal factors in selecting a smartwatch for a clinical trial involving older adults with neurodegenerative diseases. A revised framework based on our findings, and concepts from Connely (2021), Mattison (2023), and Espay (2019) et al.'s previous work, is presented as a tool for researchers in evaluation of smartwatches and future sensing technologies.

CONCLUSION: Careful consideration must be given to the fitness of technologies for future research, especially considering that this is a rapidly changing field. The process of selection of a smartwatch for a clinical trial should be thoughtful, scrutinous, and include interdisciplinary collaboration.}, } @article {pmid39851621, year = {2024}, author = {Hu, X and Yu, Y and Tu, Y and Wang, J and Chen, S and Bao, Y and Zhang, T and Xing, Y and Zheng, S}, title = {A Secure and Efficient White-Box Implementation of SM4.}, journal = {Entropy (Basel, Switzerland)}, volume = {27}, number = {1}, pages = {}, pmid = {39851621}, issn = {1099-4300}, support = {SGSC0000AQQT2400701//Laboratory Specialized Scientific Research Projects of Beijing Smart-chip Microelectronics Technology/ ; }, abstract = {Differential Computation Analysis (DCA) leverages memory traces to extract secret keys, bypassing countermeasures employed in white-box designs, such as encodings. Although researchers have made great efforts to enhance security against DCA, most solutions considerably decrease algorithmic efficiency. In our approach, the Feistel cipher SM4 is implemented by a series of table-lookup operations, and the input and output of each table are protected by affine transformations and nonlinear encodings generated randomly. We employ fourth-order non-linear encoding to reduce the loss of efficiency while utilizing a random sequence to shuffle lookup table access, thereby severing the potential link between memory data and the intermediate values of SM4. Experimental results indicate that the DCA procedure fails to retrieve the correct key. Furthermore, theoretical analysis shows that the techniques employed in our scheme effectively prevent existing algebraic attacks. Finally, our design requires only 1.44 MB of memory, significantly less than that of the known DCA-resistant schemes-Zhang et al.'s scheme (24.3 MB), Yuan et al.'s scheme (34.5 MB) and Zhao et al.'s scheme (7.8 MB). Thus, our SM4 white-box design effectively ensures security while maintaining a low memory cost.}, } @article {pmid39850295, year = {2024}, author = {Barati, M and Amouzeshi, Z and Nikraftar, F}, title = {The impact of self-care training using the teach-back method on health anxiety in patients with coronary artery disease: A randomized controlled clinical trial.}, journal = {Journal of education and health promotion}, volume = {13}, number = {}, pages = {469}, pmid = {39850295}, issn = {2277-9531}, abstract = {BACKGROUND: Coronary artery disease (CAD) is the most prevalent heart disease and a leading cause of death among both men and women. It is worth noting that anxiety is highly prevalent among patients with CAD, and it can significantly affect their overall performance and well-being. This study aimed to determine the impact of self-care training, specifically using the teach-back method, on health anxiety in patients with CAD.

MATERIALS AND METHODS: In this randomized controlled clinical trial, a total of 50 patients with coronary artery disorders were selected from the coronary care unit of Rasool Hospital in Ferdows City, Iran, in 2022. The participants were randomly assigned to two groups. The intervention group received self-care training based on the teach-back method, which consisted of three individual sessions lasting 30-45 minutes each, conducted over the course of one week. However, the control group received routine care. To collect data, the researchers utilized Salkovskis et al.'s (2002) health anxiety questionnaire. The collected data were analyzed using the Chi-square test, Fisher's exact test, independent t-test, and paired t-test at a significance level of P < 0.05.

RESULTS: Most participants in the control and intervention groups were female. The mean ages of the intervention and control groups were 47.1 ± 12.83 and 48.1 ± 44.81 years, respectively, with no statistically significant difference (P = 0.67). The results indicated that there was a statistically significant difference in the total mean score (P = 0.000) and mean scores of subscales of health anxiety (awareness of bodily sensations or changes (P = 0.001), feared consequences of having an illness (P = 0.001), and worry about health (P = 0.008)) between the two groups.

CONCLUSIONS: The self-care training based on the teach-back method reduced health anxiety in patients with CAD. Therefore, it is recommended to incorporate the teach-back method as an educational approach by nursing team to effectively reduce health anxiety in patients with CAD.}, } @article {pmid39848183, year = {2025}, author = {Hossain, SA and Murali R, M}, title = {Assessing the potential effects of climate change on the morphodynamics of the tropical coral reef islands in the Gulf of Mannar, Indian Ocean.}, journal = {Journal of environmental management}, volume = {375}, number = {}, pages = {124122}, doi = {10.1016/j.jenvman.2025.124122}, pmid = {39848183}, issn = {1095-8630}, mesh = {*Climate Change ; *Coral Reefs ; Indian Ocean ; Ecosystem ; Anthozoa ; Animals ; }, abstract = {Low-lying and small tropical coral reef islands around the world are extremely vulnerable to the effects of global environmental change caused by the combination of anthropogenic climate change and escalating extreme hydrodynamic events. Erosion and inundation are anticipated to physically destabilize the tropical coral reef islands, rendering them uninhabitable within the next century. Therefore, it is crucial to assess the repercussions of these hazardous events on the delicate reef island ecosystem in order to conserve and ensure sustainable management. Multitemporal remotely sensed Landsat satellite imageries were utilized to investigate the net and decadal morphological transformation of tropical coral reef islands in the Gulf of Mannar, Indian Ocean. Over the past half-century, these islands have consistently adapted to global environmental changes, even while local sea levels rise at a rate of 3.38 mm per year. Advanced statistical techniques, such as net shoreline movement (NSM), end point rate (EPR), and linear regression rate (LRR), were employed for estimating the shoreline change rate using a Digital Shoreline Analysis System (DSAS). In addition, the GIS-based overlay analysis methods were applied to examine the net and decadal areal (planform) changes and also utilized for estimating the inundation trajectories of reef islands under the sea level rise scenarios of 1 m and 2 m. Furthermore, time series analysis was performed to analyze the variability of critical climate-induced factors using archived reanalysis oceanographic data. In addition, linear and polynomial statistical techniques were applied to investigate the driving factors behind the coral reef island morphological transition. The findings show that two islands have already disappeared, while others have experienced a dramatic reduction in their footprint. Approximately 62.64% of the shoreline experienced significant erosion, while 36.91% witnessed gradual accretion. The Tuticorin group confronted the severe reduction in island footprint, with a significant decrease of 83.04%, followed by Keelakarai groups (33.35%), Mandapam groups (29.60%), Vembar groups (28.14%), and Rameswaram islands (3.43%). The study also predicts that the island footprint could submerge in an area of 627.30 ha and 1284.21 ha within the next century, with an expected sea level rise (SLR) of 1 m and 2 m, respectively. The study emphasizes that the combination of human-induced factors and regional coastal processes such as sea level rise and swells are the key drivers engendering the stress on the physical resilience of the coral reef islands. Urgent and continual monitoring of the reef islands is crucial for a better understanding of their dynamic trajectories and for developing nature-based solutions to catastrophic erosion. These nature-based solutions (NbS) for minimizing island erosion are initiatives that use natural ecosystems to safeguard islands while enhancing biodiversity, climate resilience, and community livelihoods. The interactions between nature-based solutions (NbS) for combating erosion, reef island resilience, and Sustainable Development Goals are evaluated based on the positive correlation, our expert knowledge, and Griggs et al.'s 2017 seven-point scale framework. The outcomes of this study may provide comprehensive insights to decision-makers and administrators for formulating and implementing policies for long-term resilience building and sustainable island management.}, } @article {pmid39843284, year = {2025}, author = {Fargier, PB and Damin-Pernik, M and Launay, M and Gagneux-Brunon, A and Bellet, F and Beyens, MN}, title = {COVID-19 infection and risk of adverse drug reactions: Cohort study.}, journal = {Therapie}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.therap.2024.12.012}, pmid = {39843284}, issn = {1958-5578}, abstract = {AIM: During coronavirus disease 2019 (COVID-19), the incidence rate of adverse drug reactions (ADRs) in hospitalized patients seemed higher than before the pandemic. Severe inflammation triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was cited as an explanation. We aimed to determine whether COVID-19 infection was associated with a higher risk of ADRs compared to other infectious diseases.

METHODS: A monocentric historic cohort, "exposed/unexposed" study, was conducted in the university hospital of Saint-Étienne (inclusion period from March 05, 2020 to April 16, 2020 for "COVID-19" and from January to December 2019 for "non-COVID-19"). All ADRs reported in patients' medical records were retrospectively assessed using Bégaud et al.'s algorithm. A multivariable Cox regression was performed to assess the hazard ratio (HR).

RESULTS: The incidence rate of 4.64 ADRs per person-month in the "COVID-19" group did not differ from the 3.52 ADRs per person-month in the "non-COVID-19" group (multivariable adjusted HR 1.29, 95% confidence interval [CI], 0.91-1.81, P=0.1436). COVID-19 patients had more hepatobiliary disorders whereas non-COVID-19 patients had more renal and urinary disorders. Classes of drugs mostly involved in ADRs occurrence were antibiotics, followed by antithrombotics in both groups. Compared to patients with no ADR, patients with ADRs had higher C-reactive protein (CRP) levels and a lower estimated glomerular filtration rate (eGFR).

CONCLUSION: In this study, the incidence rate in hospitalized patients with COVID-19 was not statistically different from that in the group with another infection. High CRP levels, as well as low eGFR, were the main risk factors for the occurrence of ADRs and should be considered in further ADR prevention strategies.}, } @article {pmid39842248, year = {2025}, author = {Micallef, C and Somanadhan, S and O'Donnell, D and Thompson, W and Stokes, D and Koe, S and Davies, C}, title = {Distraction-based interventions for children in the emergency care setting: A realist synthesis based on primary research.}, journal = {Journal of pediatric nursing}, volume = {81}, number = {}, pages = {43-54}, doi = {10.1016/j.pedn.2025.01.017}, pmid = {39842248}, issn = {1532-8449}, mesh = {Humans ; Child ; *Pain Management/methods ; *Emergency Service, Hospital ; *Anxiety/prevention & control/therapy ; Male ; Female ; *Stress, Psychological/prevention & control ; Child, Preschool ; }, abstract = {BACKGROUND: The literature underscores the prevalence of pain as the most common presenting symptom in the Emergency Care Setting (ECS) and is associated with anxiety and stress for children. On top of that painful procedures are often required as part of their treatment, making procedural pain a common experience. The substantial evidence supporting the effectiveness of distraction-based interventions (DBI) in relieving pain and anxiety and reducing stress underscores the urgency of addressing this issue. However, the fragmented adoption of standardised DBI highlights the need for further research and implementation.

PURPOSE: To conduct a realist synthesis based on primary research exploring "what works for whom under what circumstances, how and why?" when implementing DBI in the ECS.

REVIEW METHODS: Empirical research evidence was retrieved systematically from eight databases covering health and social sciences. The studies were synthesised based on the principles of realist science, drawing on Pawson and Tilley's (1997) and Dalkin et al.'s (2015) programme theory development, which explains the contexts and mechanisms that generate positive outcomes about DBI for children in the ECS.

RESULTS: Of the 2099 studies screened, 64 were included. Screening was conducted 2023 to December 2024. A synthesis of the findings generated five Programme Theories (PT). PT1 focuses on the personalisation of DBI for children in the ECS, PT2 explains the importance of parental participation, PT3 highlights the importance of healthcare workers (HCWs) commitment to adopting DBI in practice, PT4 draws attention to policy-level efforts necessary for implementation support, and PT5 focuses on engaging all stakeholders in the implementation process.

CONCLUSION: To the authors' knowledge, this is the first study to apply a realist lens to understand the use of DBI in children attending the ECS and present the mechanisms that enable and/or inhibit its implementation and utilisation in everyday clinical practice.

IMPLICATIONS TO PRACTICE: This realist synthesis provides methodological guidance in the form of PT that can be utilised by clinical practitioners to adopt and implement DBI within the healthcare setting.}, } @article {pmid39836321, year = {2025}, author = {Lazzaro, C and Bergamaschi, R and Zaffaroni, M and Totaro, R and Paolicelli, D}, title = {Matters arising: cost-utility and cost-effectiveness analysis of disease-modifying drugs of relapsing-remitting multiple sclerosis: a systematic review.}, journal = {Health economics review}, volume = {15}, number = {1}, pages = {3}, pmid = {39836321}, issn = {2191-1991}, abstract = {BACKGROUND: In their interesting systematic review, Gallehzan et al. quoted our article Cost-utility analysis of teriflunomide in naïve vs. previously treated patients with relapsing-remitting multiple sclerosis (RRMS) in Italy. While we are grateful to Gallehzan et al. for their interest in the aim of our research, we would like to clarify some points.

METHODS: We compare Gallehzan et al.'s statements about our article with the original publication.

RESULTS: Gallehzan et al. omitted or misreported some relevant methodological issues and findings presented in our article. As far as methods are concerned, the main omissions were the 7-year time horizon of our study (that falls in between the 5-10 years range mentioned by Gallehzan et al. for other contributions) and the number of simulated RRMS naïve patients (1000). Regarding findings, Gallehzan et al. mistook the 0.480 incremental Quality-Adjusted Life Year gained by RRMS naïve patients vs. RRMS experienced patients on teriflunomide for the base case Incremental Cost-Utility Ratio (ICUR) calculated according to the societal viewpoint. In fact, for both the healthcare sector and societal perspectives adopted in our Markov model-based cost-utility analysis, the baseline results showed teriflunomide in RRMS naïve patients to be strongly dominant (that is, producing more QALYs and being, at the same time, cost-saving) vs. RRMS experienced patients. Therefore, the calculation of the two ICURs was not necessary.

CONCLUSIONS: As systematic reviews play a remarkable role in disseminating health economic research, a careful description of the methods and the findings reported in the included studies is of paramount importance.}, } @article {pmid39834841, year = {2024}, author = {Coutinho, KMD and Fernandes, F and Medeiros, KC and Coutinho, KD and Dias, AP and Valentim, RAM and Leite-Lais, L and Lima, KC}, title = {Data Report: Educational pathway addressing food and nutrition in amyotrophic lateral sclerosis on the AVASUS platform.}, journal = {Frontiers in digital health}, volume = {6}, number = {}, pages = {1476293}, pmid = {39834841}, issn = {2673-253X}, } @article {pmid39833779, year = {2025}, author = {Zhang, XN and Zhang, S and Liu, CY and Ni, ZH and Lv, HT}, title = {Caregivers' experience of having a child with Down syndrome: a meta-synthesis.}, journal = {BMC nursing}, volume = {24}, number = {1}, pages = {66}, pmid = {39833779}, issn = {1472-6955}, support = {No. SKY 2023183//Suzhou Science and Technology Bureau Research Program/ ; No. SKY 2023183//Suzhou Science and Technology Bureau Research Program/ ; No. SKY 2023183//Suzhou Science and Technology Bureau Research Program/ ; No. SKY 2023183//Suzhou Science and Technology Bureau Research Program/ ; No. SKY 2023183//Suzhou Science and Technology Bureau Research Program/ ; }, abstract = {BACKGROUND: This study aimed to integrate the experiences of caregivers of children with Down syndrome during the care process and understand their feelings and needs.

METHODS: We used Page et al.'s (2021) Preferred Reporting Items for Systematic Reviews and Meta-synthesis Statement. Ten databases (Web of Science, PubMed, EMBASE, Cochrane Library, CINAHL, PsycInfo, China Biology Medicine, China National Knowledge Infrastructure, Wanfang Data, and China Science and Technology Journal Database) were searched for relevant studies published from the inception of the database to October 2023. Eight qualitative studies were analysed. The following seven themes were included: 'feeding pressure', 'hope for education', 'societal rejection and stigma', 'psychological pressure', 'caring burden', 'family burden', and 'family adaptation and self-growth'.

RESULTS: We found that feeding pressures, educational concerns, language difficulties, and discrimination and stigmatisation led to psychological, economic, and family stress in caregivers of children with Down syndrome. We document the need for strong coping mechanisms and support systems for these families from medical and psychological institutions and a need for public education and awareness.

CONCLUSIONS: We summarised the daily care experiences of caregivers of children with Down syndrome. Our findings provide a scientific basis for further research focused on reducing physical and mental pressure on caregivers and improving the quality of family life.}, } @article {pmid39833536, year = {2025}, author = {Curtis, TJ and Chant, C and Quek, S and Giarenis, I and Gray, TG}, title = {Fistulae Secondary to Vaginal Pessary Use for Pelvic Organ Prolapse: A Systematic Review.}, journal = {International urogynecology journal}, volume = {36}, number = {3}, pages = {491-521}, pmid = {39833536}, issn = {1433-3023}, mesh = {Humans ; *Pessaries/adverse effects ; Female ; *Pelvic Organ Prolapse/therapy ; Risk Factors ; *Rectovaginal Fistula/etiology/epidemiology ; Retrospective Studies ; Prevalence ; }, abstract = {INTRODUCTION AND HYPOTHESIS: Urogenital and rectovaginal fistulae are rare complications of pessary use for pelvic organ prolapse (POP). This systematic review investigates the prevalence of these complications in patients using pessary for POP, potential risk factors and approaches to their investigation and management.

METHODS: All studies in English reporting urogenital or rectovaginal fistulae secondary to pessaries for POP were eligible for inclusion. AMED, CINAHL, MedLine, Scopus and Web of Science databases were searched from inception to March 2024. Risk of bias was assessed using validated tools: Murad et al.'s tool for case series/reports and ROBINS-I for non-randomised studies. Quantitative synthesis of descriptive statistics and narrative summary were performed.

RESULTS: Two retrospective studies and 60 case series/reports were included, describing 76 fistulae (34 urogenital, 42 rectovaginal). The retrospective studies estimated the prevalence of fistulae to be 3%. Of reported fistulae, 45% occurred with Gellhorn, 16% with ring, 11% with shelf and 9% with cube pessaries. Fifty percent were associated with neglected pessary care. Conservative management resulted in size reduction or resolution in 69% of fistulae: this approach should be considered. Vaginal (88%) and abdominal (100%) vesicovaginal fistula repairs were successful. Diverting ostomies were popular for rectovaginal fistulae but often resulted in permanent stoma without reducing mortality, recurrence or repair failure. Colpocleisis represents an effective procedure for managing co-existing POP.

CONCLUSIONS: The prevalence of fistulae from pessary use is likely < 1% but may rise to 3% with risk factors present, including Gellhorn pessaries and neglected care. Both conservative and surgical management are viable treatment options.}, } @article {pmid39829831, year = {2025}, author = {Austin, GI and Korem, T}, title = {Compositional transformations can reasonably introduce phenotype-associated values into sparse features.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {39829831}, issn = {2692-8205}, support = {T15 LM007079/LM/NLM NIH HHS/United States ; }, abstract = {It was recently argued[1] that an analysis of tumor-associated microbiome data[2] is invalid because features that were originally very sparse (genera with mostly zero read counts) became associated with the phenotype following batch correction[1]. Here, we examine whether such an observation should necessarily indicate issues with processing or machine learning pipelines. We show counterexamples using the centered log ratio (CLR) transformation, which is often used for analysis of compositional microbiome data[3]. The CLR transformation has similarities to Voom-SNM[4,5], the batch-correction method brought into question[1,2], yet is a sample-wise operation that cannot, in itself, "leak" information or invalidate downstream analyses. We show that because the CLR transformation divides each value by the geometric mean of its sample, common imputation strategies for missing or zero values result in transformed features that are associated with the geometric mean. Through analyses of both synthetic and vaginal microbiome datasets we demonstrate that when the geometric mean is associated with a phenotype, sparse and CLR-transformed features will also become associated with it. We re-analyze features highlighted by Gihawi et al.[1] and demonstrate that the phenomenon of sparse features becoming phenotype-associated can also be observed after a CLR transformation, which serves as a counterexample to the claim that such an observation necessarily means information leakage. While we do not intend to address other concerns regarding tumor microbiome analyses[1,6], validate Poore et al.'s[2] results, or evaluate batch-correction pipelines, we conclude that because phenotype-associated features that were initially sparse can be created by a sample-wise transformation that cannot artifactually inflate machine learning performance, their detection is not independently sufficient to demonstrate information leakage in machine learning pipelines. Microbiome data is multivariate, and as such, a value of zero carries a different meaning for each sample. Many transformations, including CLR and other batch-correction methods, are likewise multivariate, and, as these issues demonstrate, each individual feature should be interpreted with caution.}, } @article {pmid39822898, year = {2024}, author = {Malamule, MM and Gundo, R and Mulaudzi, M}, title = {The effect of coronavirus disease 2019 vaccination on pregnant women: A scoping review.}, journal = {Health SA = SA Gesondheid}, volume = {29}, number = {}, pages = {2577}, pmid = {39822898}, issn = {2071-9736}, abstract = {BACKGROUND: Globally, reports have shown that pregnant women refuse to receive the coronavirus disease 2019 (COVID-19) vaccine. This has posed a significant concern given the global impact of the COVID-19 pandemic.

AIM: This study aims to explore the current evidence on the effect of COVID-19 vaccination on pregnant women.

METHOD: A scoping review was conducted using Levac et al.'s five-stage framework. Relevant articles were searched in the Web of Science, PubMed, Scopus and EBSCOhost (CINAHL) databases. The identified articles were screened based on predetermined inclusion and exclusion criteria. Data from the selected articles were charted and summarised into meaningful units.

RESULTS: Twelve articles from developed countries were included in the review. Studies have reported that COVID-19 vaccination during pregnancy is generally safe and does not increase the risk of pregnancy complications. There was no significant difference in delivery outcomes between vaccinated and unvaccinated women. Neonatal outcomes were not affected by the vaccination. However, one study identified a potential risk of spontaneous abortion between 6 and 9 weeks of gestation among vaccinated women.

CONCLUSION: Coronavirus disease 2019 vaccination is considered safe during pregnancy. While some studies have identified potential associations with certain conditions, the overall benefits of vaccination outweigh the risks. Continued monitoring of the safety and effectiveness of COVID-19 vaccines during pregnancy is recommended. Pregnant women should consult healthcare providers to make informed decisions regarding vaccination.

CONTRIBUTION: The findings of this review may assist in alleviating anxiety and reducing vaccine hesitancy among pregnant women.}, } @article {pmid39816800, year = {2025}, author = {Shokr, MM and Badawi, GA and Elshazly, SM and Zaki, HF and Mohamed, AF}, title = {Sigma 1 Receptor and Its Pivotal Role in Neurological Disorders.}, journal = {ACS pharmacology & translational science}, volume = {8}, number = {1}, pages = {47-65}, pmid = {39816800}, issn = {2575-9108}, abstract = {Sigma 1 receptor (S1R) is a multifunctional, ligand-activated protein located in the membranes of the endoplasmic reticulum (ER). It mediates a variety of neurological disorders, including epilepsy, amyotrophic lateral sclerosis, Alzheimer's disease, Huntington's disease. The wide neuroprotective effects of S1R agonists are achieved by a variety of pro-survival and antiapoptotic S1R-mediated signaling functions. Nonetheless, relatively little is known about the specific molecular mechanisms underlying S1R activity. Many studies on S1R protein have highlighted the importance of maintaining normal cellular homeostasis through its control of calcium and lipid exchange between the ER and mitochondria, ER-stress response, and many other mechanisms. In this review, we will discuss S1R different cellular localization and explain S1R-associated biological activity, such as its localization in the ER-plasma membrane and Mitochondrion-Associated ER Membrane interfaces. While outlining the cellular mechanisms and important binding partners involved in these processes, we also explained how the dysregulation of these pathways contributes to neurodegenerative disorders.}, } @article {pmid39815868, year = {2024}, author = {Alexander, J and Gendera, S and Robinson, S and Fisher, KR and Howe, K}, title = {On-the-job training supports for people with intellectual disability employed in aged care.}, journal = {Journal of intellectual & developmental disability}, volume = {49}, number = {2}, pages = {163-174}, doi = {10.3109/13668250.2023.2256075}, pmid = {39815868}, issn = {1469-9532}, mesh = {Humans ; *Intellectual Disability/rehabilitation ; Male ; Female ; Adult ; *Inservice Training/methods ; *Mentors ; Middle Aged ; *Health Personnel/education ; Aged ; }, abstract = {BACKGROUND: Traineeships have been proven to be beneficial vocational pathways for people with intellectual disability however to date the on-the-job training provision associated with traineeships has not been well documented.

METHOD: This study describes components of on-the-job training provided to eight people, most with intellectual disability undergoing traineeships for 12 months in four aged care services. Sheri et al.'s (2019) framework for mentors during training was used to examine the findings.

RESULTS: Challenges in the traineeships were common to most new staff, such as developing confidence, recognising the urgency of some tasks, and time to learn how to support aged-care residents. The findings highlighted on-the-job training that was individualised, incorporating a variety of approaches was most beneficial to the trainees.

CONCLUSIONS: Traineeships for people with intellectual disability require support from both the trainee and mentors. This support is essential to develop skills and ensure positive workplace attitudes.}, } @article {pmid39815448, year = {2025}, author = {Brocklehurst, P and Langley, J and Wassall, R and Daniyal, S and Syed, SS and Harvey, M and Goulden, N and Sherriff, A and Heilmann, A and Hoare, Z and Smith, C and Watt, R and O'Neill, C and Kee, F and Cairns, P and Lievesley, N and McKenna, G and Tsakos, G}, title = {A Theoretically Informed Process Evaluation in Parallel to a Feasibility Study of a Complex Oral Health Intervention Using NICE Guidelines in a Care Home Setting.}, journal = {Community dentistry and oral epidemiology}, volume = {53}, number = {2}, pages = {152-159}, pmid = {39815448}, issn = {1600-0528}, support = {//National Institute for Health and Care Research/ ; }, mesh = {Humans ; Feasibility Studies ; *Oral Health ; Interviews as Topic ; *Process Assessment, Health Care ; *Practice Guidelines as Topic ; *Home Care Services ; Qualitative Research ; *Nursing Homes ; }, abstract = {BACKGROUND: A theoretically informed process evaluation was undertaken in parallel to a study examining the feasibility of an oral health intervention based on an existing guideline for care homes. The objectives were to explore the factors that influenced the implementation of the intervention in order to understand the potential pathway to impact. The research team initially utilised Pfadenhauer et al.'s framework, which focuses on a number of different implementation factors: intervention characteristics, context, theory, process, strategy, agents, outcomes and setting.

METHODS: Nine semi-structured interviews were undertaken with care home managers and staff, predominantly within the intervention arm of the study. Interview schedules were originally based on Pfadenhauer et al.'s framework. These were coded and analysed using thematic analysis. Given the range of themes that emerged, the research team ran a reflexive workshop to determine whether Pfadenhauer et al.'s framework was able to capture and frame the authentic voice of those interviewed.

RESULTS: The research team found that a systems lens approach better fitted the data from the interviews, capturing the idiosyncrasy of the different settings and the importance of values and beliefs of the key stakeholders. It was clear that unlike the structure proposed by Pfaednhauer et al., many of the factors were interdependent and hierarchical in nature, that is, paradigm and goals within the care home had a direct impact on the system structure, which fed into how the care home was maintained, which led onto how the different actors (care home managers and staff) behaved. The process also highlighted key factors for intervention delivery: time poverty, competing needs, staff turnover, differences between shift patterns and between permanent and agency staff. Cognitive capacity of the residents and staff attitudes were also key.

CONCLUSIONS: Adding a reflexive workshop enabled the research to critically review the Pfadenhauer et al.'s framework and change to a systems lens approach, which better explained the interdependent and hierarchical nature of the findings. It also highlighted a number of key factors that could influence the pathway to impact for the intervention.

TRIAL REGISTRATION: ISRCTN10276613.}, } @article {pmid39815393, year = {2025}, author = {Arattu Thodika, AR and Pan, X and Shao, Y and Nam, K}, title = {Machine Learning Quantum Mechanical/Molecular Mechanical Potentials: Evaluating Transferability in Dihydrofolate Reductase-Catalyzed Reactions.}, journal = {Journal of chemical theory and computation}, volume = {21}, number = {2}, pages = {817-832}, pmid = {39815393}, issn = {1549-9626}, support = {R01 GM132481/GM/NIGMS NIH HHS/United States ; R35 GM153297/GM/NIGMS NIH HHS/United States ; R43 GM133270/GM/NIGMS NIH HHS/United States ; R44 GM133270/GM/NIGMS NIH HHS/United States ; }, mesh = {*Machine Learning ; *Quantum Theory ; *Tetrahydrofolate Dehydrogenase/metabolism/chemistry/genetics ; Biocatalysis ; Thermodynamics ; Molecular Dynamics Simulation ; }, abstract = {Integrating machine learning potentials (MLPs) with quantum mechanical/molecular mechanical (QM/MM) free energy simulations has emerged as a powerful approach for studying enzymatic catalysis. However, its practical application has been hindered by the time-consuming process of generating the necessary training, validation, and test data for MLP models through QM/MM simulations. Furthermore, the entire process needs to be repeated for each specific enzyme system and reaction. To overcome this bottleneck, it is required that trained MLPs exhibit transferability across different enzyme environments and reacting species, thereby eliminating the need for retraining with each new enzyme variant. In this study, we explore this potential by evaluating the transferability of a pretrained ΔMLP model across different enzyme mutations within the MM environment using the QM/MM-based ML architecture developed by Pan, X. J. Chem. Theory Comput. 2021, 17(9), 5745-5758. The study includes scenarios such as single point substitutions, a homologous enzyme from different species, and even a transition to an aqueous environment, where the last two systems have MM environment that is substantially different from that used in MLP training. The results show that the ΔMLP model effectively captures and predicts the effects of enzyme mutations on electrostatic interactions, producing reliable free energy profiles of enzyme-catalyzed reactions without the need for retraining. The study also identified notable limitations in transferability, particularly when transitioning from enzyme to water-rich MM environments. Overall, this study demonstrates the robustness of the Pan et al.'s QM/MM-based ML architecture for application to diverse enzyme systems, as well as the need for further research and the development of more sophisticated MLP models and training methods.}, } @article {pmid39813072, year = {2025}, author = {Raines, C and Mefferd, A}, title = {Disease-Specific Speech Movement Characteristics of the Tongue and Jaw.}, journal = {Journal of speech, language, and hearing research : JSLHR}, volume = {68}, number = {7S}, pages = {3544-3557}, pmid = {39813072}, issn = {1558-9102}, support = {R01 DC019648/DC/NIDCD NIH HHS/United States ; R03 DC015075/DC/NIDCD NIH HHS/United States ; T32 DC020141/DC/NIDCD NIH HHS/United States ; UL1 TR002243/TR/NCATS NIH HHS/United States ; }, mesh = {Humans ; *Tongue/physiopathology ; *Dysarthria/physiopathology/etiology ; Male ; Female ; *Jaw/physiopathology ; Middle Aged ; Aged ; Biomechanical Phenomena ; *Speech/physiology ; Parkinson Disease/physiopathology/complications ; Movement/physiology ; Multiple Sclerosis/physiopathology/complications ; Adult ; Huntington Disease/physiopathology/complications ; Amyotrophic Lateral Sclerosis/physiopathology/complications ; Range of Motion, Articular/physiology ; Speech Production Measurement ; }, abstract = {PURPOSE: To advance our understanding of disease-specific articulatory impairment patterns in speakers with dysarthria, this study investigated the articulatory performance of the tongue and jaw in speakers with differing neurological diseases (Parkinson's disease [PD], amyotrophic lateral sclerosis, multiple sclerosis, and Huntington's disease).

METHOD: Fifty-seven speakers with dysarthria and 30 controls produced the sentence "Buy Kaia a kite" five times. A three-dimensional electromagnetic articulography was used to record the articulatory movements of the posterior tongue and jaw. Sentence-length kinematic measures (e.g., duration, tongue range of motion [ROM], jaw ROM, tongue speed, jaw speed) were extracted.

RESULTS: Results revealed significant group effects for the duration, jaw ROM, and tongue speed but not for tongue ROM. Post hoc pairwise comparisons revealed more significant between-groups differences for duration and jaw ROM than for tongue speed. Statistically significant findings between clinical groups were predominantly driven by the difference between speakers with PD and speakers of other clinical groups.

CONCLUSIONS: Reduced jaw ROM and trends toward reduced tongue ROM confirm hypokinesia as a distinguishing motor feature of speakers with PD. However, deviancies in speed or movement duration did not emerge as a distinguishing motor feature for any of the four studied clinical groups. Nevertheless, movement duration, but not movement speed, may be useful to index dysarthria severity.}, } @article {pmid39800967, year = {2025}, author = {Furui, K and Shimizu, T and Akiyama, Y and Kimura, SR and Terada, Y and Ohue, M}, title = {PairMap: An Intermediate Insertion Approach for Improving the Accuracy of Relative Free Energy Perturbation Calculations for Distant Compound Transformations.}, journal = {Journal of chemical information and modeling}, volume = {65}, number = {2}, pages = {705-721}, pmid = {39800967}, issn = {1549-960X}, mesh = {*Thermodynamics ; *Drug Discovery/methods ; }, abstract = {Accurate prediction of the difference in binding free energy between compounds is crucial for reducing the high costs associated with drug discovery. Relative binding free energy perturbation (RBFEP) calculations are effective for small structural changes; however, large topological changes pose significant challenges for calculations, leading to high errors and difficulties in convergence. To address such issues, we propose a new approach─PairMap─that focuses on introducing appropriate intermediates for complex transformations between two input compounds. PairMap-generated intermediates exhaustively, determined the optimal conversion paths, and introduced thermodynamic cycles into the perturbation map to improve accuracy and reduce computational cost. PairMap succeeded in introducing appropriate intermediates that could not be discovered by existing simple approaches by comprehensively considering intermediates. Furthermore, we evaluated the accuracy of the prediction of binding free energy using 9 compounds selected from Wang et al.'s benchmark set, which included particularly complex transformations. The perturbation map generated by PairMap achieved excellent accuracy with a mean absolute error of 0.93 kcal/mol compared to 1.70 kcal/mol when using the perturbation map generated by the conventional Flare FEP intermediate introduction method. Moreover, in a scaffold hopping experiment conducted with the PDE5a target involving complex transformations, PairMap provided more accurate free energy predictions than ABFEP calculations, yielding more reliable results compared to experimental data. Additionally, PairMap can be utilized to introduce intermediates into congeneric series, demonstrating that complex links on the perturbation map can be resolved with minimal addition of intermediates and links. In conclusion, PairMap overcomes the limitations of existing methods by enabling RBFEP calculations for more complex transformations, further streamlining lead optimization in drug discovery.}, } @article {pmid39795468, year = {2024}, author = {Yao, X and Yang, X and Lu, Y and Qiu, Y and Zeng, Q}, title = {Review of the Synthesis and Degradation Mechanisms of Some Biodegradable Polymers in Natural Environments.}, journal = {Polymers}, volume = {17}, number = {1}, pages = {}, pmid = {39795468}, issn = {2073-4360}, support = {E0600591//Fujian University of Technology/ ; GY-Z23074//Fujian University of Technology/ ; JAT210285//Education Department of Fujian Province/ ; }, abstract = {The escalating demand for sustainable materials has been fueling the rapid proliferation of the biopolymer market. Biodegradable polymers within natural habitats predominantly undergo degradation mediated by microorganisms. These microorganisms secrete enzymes that cleave long-chain polymers into smaller fragments for metabolic assimilation. This review is centered around dissecting the degradation mechanisms of specific biodegradable polymers, namely PLA, starch-based polymers, and plant fiber-based polymers. Recent investigations have unveiled that PLA exhibits augmented biocompatibility when combined with HA, and its degradation is subject to the influence of enzymatic and abiotic determinants. In the case of starch-based polymers, chemical or physical modifications can modulate their degradation kinetics, as evidenced by Wang et al.'s superhydrophobic starch-based nanocomposite cryogel. For plant fiber-based polymers, the effects of temperature, humidity, and cellulose degradation on their properties, along with the implications of various treatments and additives, are probed, as exemplified by Liu et al.'s study on jute/SiO2/PP composites. Specifically, with respect to PLA, the polymerization process and the role of catalysts such as SnCl2 in governing the structure and biodegradability are expounded in detail. The degradation of PLA in SBF and its interaction with β-TCP particles constitute crucial aspects. For starch-based polymers, the enzymatic degradation catalyzed by amylase and glucosidase and the environmental impacts of temperature and humidity, in addition to the structural ramifications of amylose and amylopectin, are further elucidated. In plant fiber-based polymers, the biodegradation of cellulose and the effects of plasma treatment, electron beam irradiation, nanoparticles, and crosslinking agents on water resistance and stability are explicated with experimental substantiation. This manuscript also delineates technological accomplishments. PLA incorporated with HA demonstrates enhanced biocompatibility and finds utility in drug delivery systems. Starch-based polymers can be engineered for tailored degradation. Plant fiber-based polymers acquire water resistance and durability through specific treatments or the addition of nanoparticles, thereby widening their application spectrum. Synthetic and surface modification methodologies can be harnessed to optimize these materials. This paper also consolidates reaction conditions, research techniques, their merits, and demerits and delves into the biodegradation reaction mechanisms of these polymers. A comprehensive understanding of these degradation mechanisms is conducive to their application and progression in the context of sustainable development and environmental conservation.}, } @article {pmid39793505, year = {2025}, author = {Ansorge, L and Stejskalová, L}, title = {Water footprint which is not the water footprint: Critical review of the article by Müller et al. (2024).}, journal = {Journal of environmental management}, volume = {374}, number = {}, pages = {124038}, doi = {10.1016/j.jenvman.2025.124038}, pmid = {39793505}, issn = {1095-8630}, mesh = {Water ; *Water Supply ; }, abstract = {This paper presents a critical analysis of the article "Comparison of cooling tower blowdown and enhanced make up water treatment to minimize cooling water footprint" by Müller et al. (2024), which claims to reduce the water footprint (WF) of cooling circuits. The WF concept, introduced in 2002, has evolved with two main approaches: the "volumetric" approach, quantifying water consumption, and the "impact-oriented" approach, assessing impacts associated with water usage. Müller et al.'s method is examined against these established methodologies. The analysis reveals that Müller et al. do not specify their WF approach, but their calculation suggests a "volumetric" WF focus. They claim WF reduction by minimizing cooling tower make-up water and blowdown discharge. However, this does not necessarily reduce the blue WF, as blowdown is typically a return flow that is not included in WF calculations unless it is discharged to another watershed or during a different period. Additionally, the grey WF impact is unclear due to insufficient data on pollutant concentrations in discharged water. The article also does not mention any characterization models or impact categories, making it unlikely that an "impact-oriented" WF approach was used. In conclusion, Müller et al.'s study does not align with established "volumetric" or "impact-oriented" WF methodologies. Instead of reducing water consumption (WF), it focuses on reducing water withdrawals. The use of the term "water footprint" appears to be a misapplication, taking advantage of its popularity. This misuse may mislead readers and underscores the need for rigorous review and critical assessment of published papers.}, } @article {pmid39789117, year = {2025}, author = {Heydari, K and Enichen, EJ and Wang, S and Nickel, GC and Kvedar, JC}, title = {A novel model for retinal imaging in the diagnosis of Alzheimer's disease.}, journal = {NPJ digital medicine}, volume = {8}, number = {1}, pages = {19}, pmid = {39789117}, issn = {2398-6352}, abstract = {Alzheimer’s disease is the fifth-leading cause of death for adults over the age of 65. Retinal imaging has emerged to find more accurate diagnostic tool for Alzheimer’s Disease. This paper highlights Hao et al.’s development of a new deep learning tool, EyeAD, which studies Optical Coherence Tomography Angiography (OCT-A) of patients with Alzheimer’s. Integrating this model into clinical workflows may offer novel insights into the progression of this disease.}, } @article {pmid39787049, year = {2025}, author = {Gurung, S and Chaudhury, H}, title = {Relationship-Centered Care for Older Adults in Long-Term Care Homes: A Scoping Review.}, journal = {Journal of applied gerontology : the official journal of the Southern Gerontological Society}, volume = {44}, number = {9}, pages = {7334648241309761}, pmid = {39787049}, issn = {1552-4523}, abstract = {This scoping review, following Levac et al.'s methodology, examines the implementation and impact of relationship-centered care (RCC) in long-term care (LTC) settings for older adults. Peer-reviewed articles from AgeLine, CINAHL Complete, MEDLINE, PsycINFO, and Web of Science were included if published after 2000, involved older adults in LTC homes, focused on RCC, and conducted in Australia, Europe, New Zealand, or North America. Key findings were organized using inductive content analysis, and 41 empirical studies with qualitative, quantitative, and mixed-methods designs were included. Three categories emerged: (1) Core Practices of RCC-relationship building and reciprocal exchange; (2) Transformative Impacts of RCC-improved care quality and collaboration; and (3) Pathways and Roadblocks to RCC-individual and organizational factors. By understanding the key elements, facilitators, and barriers of RCC, policymakers and practitioners can develop targeted strategies to improve care experiences and outcomes for residents, families, staff, and all others involved in LTC.}, } @article {pmid39779598, year = {2025}, author = {Liu, Y and Chen, S and Yang, Y}, title = {Semantic alignment: A measure to quantify the degree of semantic equivalence for English-Chinese translation equivalents based on distributional semantics.}, journal = {Behavior research methods}, volume = {57}, number = {1}, pages = {51}, pmid = {39779598}, issn = {1554-3528}, support = {21BYY114//The National Social Science Fund of China/ ; }, mesh = {*Semantics ; Humans ; *Multilingualism ; Language ; Translations ; Translating ; Psycholinguistics/methods ; East Asian People ; }, abstract = {The degree of semantic equivalence of translation pairs is typically measured by asking bilinguals to rate the semantic similarity of them or comparing the number and meaning of dictionary entries. Such measures are subjective, labor-intensive, and unable to capture the fine-grained variation in the degree of semantic equivalence. Thompson et al. (in Nature Human Behaviour, 4(10), 1029-1038, 2020) propose a computational method to quantify the extent to which translation equivalents are semantically aligned by measuring the contextual use across languages. Here, we refine this method to quantify semantic alignment of English-Chinese translation equivalents using word2vec based on the proposal that the degree of similarity between the contexts associated with a word and those of its multiple translations vary continuously. We validate our measure using semantic alignment from GloVe and fastText, and data from two behavioral datasets. The consistency of semantic alignment induced across different models confirms the robustness of our method. We demonstrate that semantic alignment not only reflects human semantic similarity judgment of translation equivalents but also captures bilinguals' usage frequency of translations. We also show that our method is more cognitively plausible than Thompson et al.'s method. Furthermore, the correlations between semantic alignment and key psycholinguistic factors mirror those between human-rated semantic similarity and these variables, indicating that computed semantic alignment reflects the degree of semantic overlap of translation equivalents in the bilingual mental lexicon. We further provide the largest English-Chinese translation equivalent dataset to date, encompassing 50,088 translation pairs for 15,734 English words, their dominant Chinese translation equivalents, and their semantic alignment Rc values.}, } @article {pmid39779285, year = {2025}, author = {Sreedharan, SE and Surendran, M and Krishnan, AS and Sylaja, PN}, title = {Reversible Cerebral Vasoconstriction Syndrome: A Retrospective study from South India.}, journal = {Annals of Indian Academy of Neurology}, volume = {28}, number = {1}, pages = {87-91}, pmid = {39779285}, issn = {0972-2327}, abstract = {BACKGROUND AND OBJECTIVES: Reversible cerebral vasoconstriction syndrome (RCVS) is a rare cause of stroke characterized by headache, seizures, focal deficits, or encephalopathy. Very little is known about this rare condition from the Indian subcontinent. Here, we present the clinical and imaging characteristics and short-term outcomes of RCVS patients from South India.

METHODS: A single-center retrospective study of all consecutive subjects with a clinical-radiological diagnosis of RCVS from January 2014 to December 2023 with a 3-month completed follow-up was conducted. The clinical features, vascular imaging patterns, and outcomes of patients with ischemic and hemorrhagic forms of RCVS were compared.

RESULTS: Of the 22 patients who fulfilled Calabrese et al.'s criteria for RCVS, the majority were women with a mean age of 47.59 (±13.55) years. While headache was the most common presenting symptom in our cohort (18/22, 81.81%), 14/22 (63.6%) developed focal neurologic deficits during the course of illness. Four of 22 patients (18%) did not report headaches during the course of illness. The most common imaging finding at presentation was cortical subarachnoid hemorrhage (SAH) in 9/22 (40.9%), followed by infarcts in 6/22, (27.2%), while 12/22 (54.5%) patients developed new ischemic lesions on repeat imaging. Ischemic and hemorrhagic presentations of RCVS did not differ in terms of clinical presentation or outcome. All patients with ischemic lesions showed diffuse vasospasm on imaging, while those with SAH had both diffuse and focal vascular abnormalities.

CONCLUSIONS: We present the largest single series of RCVS from India, with a favorable short-term outcome. Although the most common vascular abnormality is diffuse vasospasm, it can remain focal in a quarter of patients.}, } @article {pmid39775365, year = {2025}, author = {Aiello, EN and Verde, F and Curti, B and De Luca, G and Diana, L and Sirtori, MA and Maranzano, A and Curatoli, C and Zanin, A and Camporeale, E and Gnesa, A and Silani, V and Bolognini, N and Ticozzi, N and Poletti, B}, title = {Screening properties of the updated normative framework for the Italian MMSE in MCI and dementia.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {46}, number = {5}, pages = {2073-2080}, pmid = {39775365}, issn = {1590-3478}, support = {Ministero della Salute//Ministero della Salute/ ; }, mesh = {Humans ; *Cognitive Dysfunction/diagnosis/etiology ; Female ; Male ; Aged ; *Dementia/diagnosis/etiology ; Italy ; *Mental Status and Dementia Tests/standards ; Retrospective Studies ; Aged, 80 and over ; Middle Aged ; ROC Curve ; Neuropsychological Tests ; }, abstract = {BACKGROUND: This study aimed to assess the screening properties of Foderaro et al.s' updated normative framework for the Italian MMSE in detecting mild cognitive impairment (MCI) and dementia due to neurodegenerative, chronic cerebrovascular, and mixed etiologies, as well as in differentiating between these two syndromes.

METHODS: Data on 234 patients with either MCI (N = 83) or dementia (N = 151) due to Alzheimer's disease (N = 112), Lewy body disease (N = 11), frontotemporal lobar degeneration (N = 20), chronic cerebrovascular disease (N = 39), or mixed (N = 47) etiologies having been administered Foderaro et al.'s version of the MMSE were retrospectively recruited. Moreover, N = 247 healthy controls (HCs) with a normal Montreal Cognitive Assessment performance were prospectively recruited. Receiver-operating characteristics analyses were run to test the capability of both raw and demographically adjusted MMSE scores to discriminate both HCs from MCI/dementia and MCI from dementia. For these comparisons, screening metrics were also computed at Foderaro et al.'s cut-off (<26.02).

RESULTS: The capability of demographically adjusted MMSE scores to discriminate both HCs from dementia and MCI from dementia was excellent (AUC = 0.91 and 0.93, respectively), whilst good for MCI case-finding (AUC = 0.85). Consistently, the screening metrics associated with the cut-off at hand were optimal-to-excellent for dementia case-finding (sensitivity = 0.95; specificity = 0.99) and for the differentiation between MCI and dementia (sensitivity = 0.95; specificity = 0.64), whilst imbalanced for detecting MCI (sensitivity = 0.35; specificity = 0.99).

DISCUSSION: Foderaro et al.'s updated normative framework for the Italian MMSE has optimal screening properties for both dementia case-finding and the discrimination between MCI and dementia, being at variance unbalanced towards specificity when it comes to detecting MCI.}, } @article {pmid39768645, year = {2024}, author = {Onafowokan, OO and Lafage, R and Tretiakov, P and Smith, JS and Line, BG and Diebo, BG and Daniels, AH and Gum, JL and Protopsaltis, TS and Hamilton, DK and Buell, T and Soroceanu, A and Scheer, J and Eastlack, RK and Mullin, JP and Mundis, G and Hosogane, N and Yagi, M and Anand, N and Okonkwo, DO and Wang, MY and Klineberg, EO and Kebaish, KM and Lewis, S and Hostin, R and Gupta, MC and Lenke, LG and Kim, HJ and Ames, CP and Shaffrey, CI and Bess, S and Schwab, FJ and Lafage, V and Burton, D and Passias, PG and , }, title = {Comparative Analysis of Outcomes in Adult Spinal Deformity Patients with Proximal Junctional Kyphosis or Failure Initially Fused to Upper Versus Lower Thoracic Spine.}, journal = {Journal of clinical medicine}, volume = {13}, number = {24}, pages = {}, pmid = {39768645}, issn = {2077-0383}, abstract = {Background: Patients with proximal junctional kyphosis (PJK) or failure (PJF) may demonstrate disparate outcomes and recovery when fused to the upper (UT) versus lower (LT) thoracic spine. Few studies have distinguished the reoperation and recovery abilities of patients with PJK or PJF when fused to the upper (UT) versus lower (LT) thoracic spine. Methods: Adult spine deformity patients ≥ 18 yrs with preoperative and 5-year (5Y) data fused to the sacrum/pelvis were included. The rates of PJK, PJK revision, and radiographic PJF were compared between patients with upper instrumented vertebra (UIV) in the upper thoracic spine (UT; T1-T7) and lower thoracic spine (LT; T8-L1). Mean differences were assessed via analyses of covariance, factoring in any differences between cohorts at baseline and any use of PJF prophylaxis. Backstep logistic regressions assessed predictors of achieving Smith et al.'s Best Clinical Outcomes (BCOs) and complications, controlling for similar covariates. Results: A total of 232 ASD patients were included (64.2 ± 10.2 years, 78% female); 36.3% were UT and 63.7% were LT. Postoperatively, the rates of PJK for UT were lower than LT at 1Y (34.6 vs. 50.4%, p = 0.024), 2Y (29.5 vs. 49.6% (p = 0.003), and 5Y (48.7 vs. 62.8%, p = 0.048), with comparable rates of PJF. In total, 4.0% of UT patients underwent subsequent reoperation, compared to 13.0% of LT patients (p = 0.025). A total of 6.0% of patients had recurrent PJK, and 3.9% had recurrent PJF (both p > 0.05). After reoperation, UT patients reported higher rates of improvement in the minimum clinically important difference for ODI by 2Y (p = 0.007) and last follow-up (p < 0.001). While adjusted regression revealed that, for UT patients, the minimization of construct extension was predictive of achieving BCOs by last follow-up (model p < 0.001), no such relationship was identified in LT patients. Conclusions: Patients initially fused to the lower thoracic spine demonstrate an increased incidence of PJK and lower rates of disability improvement, but are at a lessened risk of neurologic complications if reoperation is required.}, } @article {pmid39749367, year = {2025}, author = {Bhardwaj, G and Smitha, MV and Jelly, P and Stephen, S and Cook, JE and Panda, S}, title = {Breastfeeding Challenges Experienced by Mothers Following Multiple Births-a Systematic Review and Meta-Synthesis of Quantitative, Qualitative, and Mixed-Methods Studies.}, journal = {Breastfeeding medicine : the official journal of the Academy of Breastfeeding Medicine}, volume = {20}, number = {4}, pages = {219-230}, doi = {10.1089/bfm.2024.0207}, pmid = {39749367}, issn = {1556-8342}, mesh = {Female ; Humans ; Infant, Newborn ; Pregnancy ; *Breast Feeding/psychology ; *Mothers/psychology ; *Multiple Birth Offspring/psychology ; Qualitative Research ; Twins ; }, abstract = {Background: Breastfeeding is vital for infant nutrition, especially for multiple babies (twins) born prematurely, yet breastfeeding rates among mothers of twins are lower compared with mothers of singleton babies. This review presents a synthesis of research findings on breastfeeding challenges experienced by mothers following twins' births. Methods: The electronic databases of CINAHL, MEDLINE, PsycINFO, EMBASE, and Web of Science were systematically searched in August 2023. All eligible quantitative, qualitative, and mixed-methods studies reported on breastfeeding challenges experienced by mothers of twins were included. The review adhered to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and followed Lucas et al.'s framework for thematic synthesis. Two reviewers independently screened all studies by title, abstract, and full text. The methodological quality of studies was independently assessed by two reviewers using the Joanna Briggs Institute critical appraisal tool and mixed-methods appraisal tool based on study design. Results: The review included 16 studies: quantitative (n = 5), qualitative (n = 8), and mixed methods (n = 3), published between 1980 and 2022, involving 3,351 mothers from 16 countries. Three main themes were generated as follows: (1) transitioning to a new role, finding the balance between self and the newborns' needs; (2) the inevitability of emotional challenges; and (3) navigating support and information. Conclusion: The integrated findings of quantitative, qualitative, and mixed-methods studies on challenges experienced by mothers of twins will have scope for researchers to address the challenges through tailored intervention, education, and support and can help health care professionals revisit policy and practices to extend support services for mothers of twins beyond the initial postpartum and to the community for improving breastfeeding practices among mothers following multiple births.}, } @article {pmid39747860, year = {2025}, author = {Bagherinia, M and Rezaeian, S and Shakiba, E and Maleki, R and Mohammad Karimi Mazhin, A and Darvishigilan, H and Janatolmakan, M and Karami, B}, title = {Analysis of the mediating role of life style in the relationship between health literacy and self-rated health employing structural equation modeling.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {283}, pmid = {39747860}, issn = {2045-2322}, mesh = {Humans ; *Health Literacy ; Adult ; Middle Aged ; Female ; Male ; Aged ; Adolescent ; Cross-Sectional Studies ; Young Adult ; *Life Style ; Surveys and Questionnaires ; Latent Class Analysis ; Health Status ; Self Report ; }, abstract = {Self-rated health is related to the reduction of the burden of diseases and health outcomes. Various factors affect self-rated health. This study aimed to investigate the mediating role of life style in the relationship between health literacy and self-rated health. In 2023, 495 people aged 18-65 participated in this cross-sectional study. Montazeri et al.'s health literacy questionnaire, Eshaghi et al.'s healthy life style assessment questionnaire, and the self-rated health (SRH) questionnaire developed by the World Health Organization were used. The structural equation modeling (SEM) was used. Statistical analysis of data was performed using Stata version 14.2 software. Based on the results, a significant total effect of health literacy on self-rated health (β = - 0.27,p = 0.001), was identified. Life style (β = - 0.20) had a direct effect on self-rated health (p < 0.001). The result from SEM indicated that health literacy exhibited a direct effect on life style (β = 0.72). In addition, the principal hypothesis of this research posits the mediating function of lifestyle within the interrelationship between the two constructs of health literacy and self-rated health. Considering the mediating role of life style in the relationship between health literacy and self-rated health, to improve self-rated health, in addition to paying attention to the role of health literacy, it is necessary to take effective measures to positively change people's lifestyle.}, } @article {pmid39743215, year = {2024}, author = {Chiu, Y and Xia, S and Qiao, H and Zhao, Z}, title = {Genetically Engineered Mouse Models for Alzheimer Disease and Frontotemporal Dementia: New Insights from Single-Cell and Spatial Transcriptomics.}, journal = {The American journal of pathology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ajpath.2024.11.006}, pmid = {39743215}, issn = {1525-2191}, support = {R21 AG066090/AG/NIA NIH HHS/United States ; R56 AG082361/AG/NIA NIH HHS/United States ; R61 NS137365/NS/NINDS NIH HHS/United States ; R01 AG089640/AG/NIA NIH HHS/United States ; R03 AG063287/AG/NIA NIH HHS/United States ; R01 AG089756/AG/NIA NIH HHS/United States ; R01 AG061288/AG/NIA NIH HHS/United States ; }, abstract = {Neurodegenerative diseases, including Alzheimer disease, frontotemporal dementia, Parkinson disease, Huntington disease, and amyotrophic lateral sclerosis, are often casually linked to protein aggregation and inclusion. As the origins of those proteinopathies have been biochemically traced and genetically mapped, genetically engineered animal models carrying the specific mutations or variants are widely used for investigating the etiology of these diseases, as well as for testing potential therapeutics. This article focuses on the mouse models of Alzheimer disease and closely related frontotemporal dementia, particularly the ones that have provided most valuable knowledge, or are in a trajectory of doing so. More importantly, some of the major findings from these models are summarized, based on the recent single-cell transcriptomics, multiomics, and spatial transcriptomics studies. While no model is perfect, it is hoped that the new insights from these models and the practical use of these models will continue to help to establish a path forward.}, } @article {pmid39734637, year = {2024}, author = {Dave, J and Hakkinen, I and Zhang, P}, title = {Comprehensive list of preventative migraine headache medications without significant drug-drug interactions.}, journal = {Frontiers in neurology}, volume = {15}, number = {}, pages = {1527897}, pmid = {39734637}, issn = {1664-2295}, abstract = {BACKGROUND/OBJECTIVE: Preventive medications are crucial in migraine prevention. In cases of refractory migraine headaches, multiple medications may be required. We seek to identify a comprehensive list of preventive migraine headache medications that can be used as two, three, and four drug combinations without drug-drug interactions.

METHODS: We compiled a list of prevention medications from Szperka et al.'s "Migraine Care in the Era of COVID-19" as well as American Headache Society's 2018 and 2021 "Consensus Statements on Integrating New Migraine Treatments into Clinical Practice." We obtained all possible two to four combinations of prevention medications through this list. We then filtered out all combinations containing at least one interaction based on DrugBank database and also identified least to most interacting medications.

RESULTS: A total of 26 unique prevention medications are identified. This results in a total of 325 combinations of two preventives, 2,600 combinations of three preventives, and 14,950 combinations of four preventives. There are a total of 124, 146, and 0 non-interacting two, three, and four preventive combinations, respectively. All except 16 combinations of pick-twos can be placed within a pick-three combinations. The resulting distinct non-interacting medications can be represented by a condensed list of 162 unique combinations of medications. CGRP antagonists, Botulinum toxin A, melatonin, and candesartan are least interacting.

CONCLUSION: This list of migraine preventive medications without drug-drug interactions is a useful tool for clinicians seeking to manage refractory headaches more effectively by implementing an evidence-based polypharmacy.}, } @article {pmid39727293, year = {2025}, author = {Gefen, N and Mazer, B and Krasovsky, T and Weiss, PL}, title = {Novel rehabilitation technologies in pediatric rehabilitation: knowledge towards translation.}, journal = {Disability and rehabilitation. Assistive technology}, volume = {20}, number = {5}, pages = {1209-1218}, doi = {10.1080/17483107.2024.2445017}, pmid = {39727293}, issn = {1748-3115}, mesh = {Humans ; Child ; *Self-Help Devices ; *Children with Disabilities/rehabilitation ; *Translational Research, Biomedical ; Telerehabilitation ; Brain-Computer Interfaces ; Robotics ; }, abstract = {PURPOSE: Knowledge translation (KT) refers to the process of applying the most promising research outcomes into practice to ensure that new discoveries and innovations improve healthcare accessibility, effectiveness, and accountability. The objective of this perspective paper is to discuss and illustrate via examples how the KT process can be implemented in an era of rapid advancement in rehabilitation technologies that have the potential to significantly impact pediatric healthcare.

METHODS: Using Graham et al.'s (2006) Knowledge-to-Action cycle, which includes the knowledge creation funnel and the action cycle, we illustrate its application in implementing novel technologies into clinical practice and informing healthcare policy changes. We explore three successful applications of technology research: powered mobility, head support systems, and telerehabilitation. Additionally, we examine less clinically mature technologies such as brain-computer interfaces and robotic assistive devices, which are hindered by cost, robustness, and ease-of-use issues.

CONCLUSIONS: The paper concludes by discussing how technology acceptance and usage in clinical settings are influenced by various barriers and facilitators at different stakeholder levels, including clients, families, clinicians, management, researchers, developers, and society. Recommendations include focusing on early and ongoing design partnerships, transitioning from research to real-life implementation, and identifying optimal timing for clinical adoption of new technologies.}, } @article {pmid39723480, year = {2025}, author = {Lydecker, JA}, title = {The Need to Increase Help-Seeking for Eating Disorders in General and Binge-Eating Disorder Specifically: Commentary on Ali et al.'s (2024) Meta-Analysis.}, journal = {The International journal of eating disorders}, volume = {58}, number = {3}, pages = {514-517}, pmid = {39723480}, issn = {1098-108X}, support = {K23 DK115893/DK/NIDDK NIH HHS/United States ; }, mesh = {Humans ; *Binge-Eating Disorder/therapy/psychology ; *Feeding and Eating Disorders/therapy/psychology ; *Help-Seeking Behavior ; Meta-Analysis as Topic ; *Patient Acceptance of Health Care ; }, abstract = {Ali et al.'s (2025) systematic review and meta-analysis updated a previous meta-analysis on the gap between the need for eating disorder treatment and rates of seeking and receiving eating disorder treatment. They found that less than one-third of individuals with eating disorders sought help for their eating disorder, which was an improvement of only 8% over more than a decade. This updated analysis makes it apparent that we need to dedicate research and resources to meeting this treatment need. Building on this work, this commentary reviews changes in help-seeking behaviors, particularly online help-seeking. The commentary also discusses binge-eating disorder (BED) help-seeking because the addition of BED as a diagnosis occurred in the time between the original and updated meta-analysis. Barriers to seeking eating disorder treatment, including identifying behaviors as indicative of an eating disorder and problematic, appear pronounced among individuals with BED. The commentary concludes by highlighting that it is essential to direct research and policy efforts along multiple pathways to close the gap between those who need and those who seek eating disorder treatment.}, } @article {pmid39718020, year = {2025}, author = {Kajee, N and Archer, E}, title = {Beyond one-size-fits-all: Reimagining well-being programmes in medical education through student expectations and agency.}, journal = {Medical education}, volume = {59}, number = {3}, pages = {258-260}, pmid = {39718020}, issn = {1365-2923}, support = {//Rhodes Trust/ ; }, abstract = {Kajee & Archer comment on Tan et al.'s exploration of student well‐being programs, outlining additional implications for medical schools.}, } @article {pmid39717339, year = {2024}, author = {Peterson, T and AbouAssaly, J and Burgin, S and Sherwin, R and Strale, F}, title = {Long-Term Effects of Neurofeedback and Hyperbaric Oxygen Therapy on Traumatic Brain Injury: A Principal Component Analysis (PCA)-Based Secondary Analysis.}, journal = {Cureus}, volume = {16}, number = {11}, pages = {e74305}, pmid = {39717339}, issn = {2168-8184}, abstract = {Severe traumatic brain injury (TBI) poses significant public health challenges, but treatments like neurofeedback and hyperbaric oxygen therapy (HBOT) show promise in aiding recovery. Neurofeedback enhances brain healing through operant conditioning, while HBOT increases cerebral oxygenation, supporting cognitive recovery. A 33-year-old woman, after suffering a severe TBI in 2018 and a long rehabilitation, began HBOT and neurofeedback in late 2021. By early 2022, she demonstrated significant cognitive, emotional, and social improvements. After numerous sessions, a June 2024 quantitative electroencephalogram (qEEG) revealed substantial brain recovery, with marked gains (Peterson et al.'s initial study) in daily functioning and specific tasks. This secondary analysis conducted in November 2024 used principal component analysis (PCA) on the initial pretest, posttest, and difference score data from the treatment period to explore the neurophysiological effects of the combined therapies. The results showed notable factor structure differences in brainwave patterns and electrode activity from the pretest to the posttest. The simpler structure observed in pretests evolved into a more complex factor structure with posttest and difference scores, indicating neurophysiological adaptations due to the interventions. This study's PCA findings align with the post-treatment qEEG statistical results conducted in June 2024 (Peterson et al.'s initial study), which identified moderate to large improvement effect sizes in the patient's brain's average frequency band parameters (g = 0.612) and small to moderate effect sizes on 19 electrode placement outcomes (uV[2] g = 0.339 and Hz g = 0.333). The June 2024 results indicated significant progress over a 31-month treatment period. In June 2024, the Disability Rating Scale (DRS) and the Glasgow Outcome Scale Extended (GOSE) showed substantial improvements in cognitive abilities such as feeding, toileting, grooming, and communication skills. According to the qEEG effect sizes, as well as DRS and GOSE scores from the pretest (2021) and posttest (2024), the patient demonstrated meaningful gains in brain recovery and overall quality of life. The cognitive improvements identified in the June 2024 Wilcoxon test were further corroborated by the factor structure analysis conducted in the November 2024 PCA. This alignment between the Wilcoxon test results and the PCA findings underscores the robustness of the observed cognitive gains, providing a comprehensive validation of the patient's progress. The consistency across these distinct analytical methods highlights the significant strides made in cognitive function, reinforcing the efficacy of the treatment regimen over the observed period.}, } @article {pmid39715366, year = {2024}, author = {Eisenberg, N and Spinrad, TL and Hernández, MM and Zuffianò, A}, title = {Top-down self-regulation as a core construct in children's and adolescents' optimal development.}, journal = {The American psychologist}, volume = {79}, number = {9}, pages = {1255-1268}, doi = {10.1037/amp0001408}, pmid = {39715366}, issn = {1935-990X}, support = {//American Institutes for Research's Equity Initiative/ ; //Bill and Melinda Gates Foundation/ ; //Progetto di Ricerca di Rilevante Interesse Nazionale/ ; }, mesh = {Humans ; *Self-Control ; Child ; Adolescent ; *Child Development ; Adolescent Development ; Social Skills ; }, abstract = {Research and theory on the role of top-down self-regulation (TDSR) in children's developmental outcomes has received considerable attention in the last few decades. In this review, we distinguish TDSR (and overlapping self-regulatory processes) from bottom-up regulation. With a particular focus on Eisenberg et al.'s body of work, we review evidence for the role of individual differences in children's TDSR to a variety of developmental outcomes. Children's TDSR processes are consistently inversely related to externalizing problems and internalizing problems, although less consistently for the latter. Moreover, TDSR processes are positively associated with social competence, empathy-related responding and prosocial outcomes, and school-related outcomes. We briefly review complexities in these associations, such as bidirectional relations, mediators, and moderators. Key areas for future work are also discussed. (PsycInfo Database Record (c) 2024 APA, all rights reserved).}, } @article {pmid39710436, year = {2025}, author = {Oddleifson, C and Kilgus, S and Klingbeil, DA and Latham, AD and Kim, JS and Vengurlekar, IN}, title = {Using a naive Bayesian approach to identify academic risk based on multiple sources: A conceptual replication.}, journal = {Journal of school psychology}, volume = {108}, number = {}, pages = {101397}, doi = {10.1016/j.jsp.2024.101397}, pmid = {39710436}, issn = {1873-3506}, support = {R305B200026//US Department of Education/ ; R305A210019//US Department of Edcuation/ ; }, mesh = {Humans ; *Bayes Theorem ; Male ; Female ; Child ; *Students/psychology ; *Schools ; Academic Success ; Educational Measurement/methods ; Academic Performance ; Risk Assessment/methods ; }, abstract = {The purpose of this study was to conduct a conceptual replication of Pendergast et al.'s (2018) study that examined the diagnostic accuracy of a nomogram procedure, also known as a naive Bayesian approach. The specific naive Bayesian approach combined academic and social-emotional and behavioral (SEB) screening data to predict student performance on a state end-of-year achievement test. Study data were collected in a large suburban school district in the Midwest across 2 school years and 19 elementary schools. Participants included 5753 students in Grades 3-5. Academic screening data included aimswebPlus reading and math composite scores. SEB screening data included Academic Behavior subscale scores from the Social, Academic, and Emotional Behavior Risk Screener. Criterion scores were derived from the Missouri Assessment Program (MAP) tests of English Language Arts and Mathematics. The performance of each individual screener was compared to the naive Bayesian approach that integrated pre-test probability information (i.e., district-wide base rates of risk derived from prior year MAP test scores), academic screening scores, and SEB screening scores. Post-test probability scores were then evaluated using a threshold model (VanDerHeyden, 2013) to determine the percentage of students within the sample that could be differentiated in terms of ruling in or ruling out intervention versus those who remained undifferentiated (as indicated by the need for additional assessment to determine risk status). Results indicated that the naive Bayesian approach tended to perform similarly to individual aimswebPlus measures, with all approaches yielding a large percentage (65%-87%) of undifferentiated students when predicting proficient performance. Overall, the results indicated that we likely failed to replicate the findings of the original study. Limitations and future directions for research are discussed.}, } @article {pmid39707498, year = {2024}, author = {Aagesen, M and Pilegaard, MS and Janssens, A and Hauken, MA and Cour, K}, title = {Development of a rehabilitation programme for young adult cancer survivors using co-production.}, journal = {Research involvement and engagement}, volume = {10}, number = {1}, pages = {134}, pmid = {39707498}, issn = {2056-7529}, support = {R224-A13434//Kræftens Bekæmpelse/ ; 19/37135//Region Syddanmark/ ; }, abstract = {BACKGROUND: Young adult cancer survivors, defined as individuals aged 18-39 who have completed primary curative treatment, face numerous age-specific biopsychosocial late effects that impact health-related quality of life negatively. Rehabilitation can enhance participation in life roles, work, leisure activities and health-related quality of life. However, there is a lack of age-specific cancer rehabilitation for this population, leaving many young adults with diminished self-efficacy in managing their challenges, resulting in unmet needs. This study aimed to co-produce and develop an age-specific, municipality-based cancer rehabilitation intervention programme to improve young adults' self-efficacy and health-related quality of life.

METHODS: The development process was completed between September 2019 and June 2023 and followed Hawkins et al.'s three-staged framework for co-production: (1) A literature review and stakeholder consultations; (2) four workshops with 2-6 young adult cancer survivors, 3-4 professionals, and two researchers and one workshop with 20 young adult cancer survivors and two researchers to co-produce the name, component content, delivery methods and potential outcomes; and (3) Refinement of the programme and its programme theory. Key findings from each stage informed the subsequent stages.

RESULTS: The Young Adults Taking ACtion programme was developed. It applies a person-centred approach and is grounded in social cognitive theory and experiential learning theory. It comprises one mandatory component, a needs assessment and goal setting that tailor which of the following seven components the young adults will receive: (1) everyday life, (2) physical activity, (3) psychological issues, (4) education and work, (5) sexuality and relationships, (6) funds and grants, and (7) family and friends. The programme is primarily group-based and will be delivered by an interdisciplinary team over 16 weeks.

CONCLUSIONS: We co-produced a comprehensive, goal-oriented, and peer-based rehabilitation programme for young adult cancer survivors. The engagement of young adults and professionals ensured that the programme aligned with the population's needs and preferences and was context specific. Thus, it is likely that the programme will be more realistic and feasible to implement in clinical practice.}, } @article {pmid39696782, year = {2025}, author = {Gause, G and Sehularo, LA and Matsipane, MJ}, title = {A Conceptual Framework to Improve Resilience Among Undergraduate First-Year Nursing Students: A Mixed-Methods Study.}, journal = {International journal of mental health nursing}, volume = {34}, number = {1}, pages = {}, pmid = {39696782}, issn = {1447-0349}, support = {//University Capacity Development Grant/ ; //Health and Welfare Sector Education and Training Authority/ ; }, mesh = {Humans ; *Resilience, Psychological ; *Students, Nursing/psychology ; South Africa ; Female ; Male ; Education, Nursing, Baccalaureate/methods ; Young Adult ; Adult ; }, abstract = {It is generally presumed that most undergraduate first-year nursing students are not prepared for the transition from basic to higher education. Resilience is recommended as a viable coping strategy that acts as a buffer to the adversities that undergraduate first-year nursing students experience. Therefore, the aim of this study was to develop and validate a conceptual framework to improve resilience among undergraduate first-year nursing students at a South African university. A multiphase concurrent mixed-methods research design was followed through concept analysis, and the empirical, development and validation phases. Development and validation of a conceptual framework were guided by Dickoff et al.'s practice-oriented theory model and e-Delphi, respectively. Data used for development of the conceptual framework were gathered from undergraduate first-year nursing students from two campuses of a South African university, while national and international experts in nursing education were used to validate a conceptual framework. The conceptual framework developed shows that the undergraduate first-year nursing students are at the centre of four contexts, namely South African university, work-integrated clinical facilities, the South African Nursing Council and South African higher education. The conceptual framework includes collaboration of stakeholders, mentoring and debriefing. The guiding principles of the conceptual framework encompass strengthening internal resources and establishment of a support group to achieve the terminus, which is characterised by undergraduate nursing students' improved transition from basic to higher education. In conclusion, the newly developed conceptual framework has the potential to improve resilience among undergraduate first-year nursing students.}, } @article {pmid39696529, year = {2024}, author = {Geng, Z and Tong, Y and Chen, Y and Wang, J and Liu, Z and Miao, J and Li, R}, title = {Investigating the causal relationship between immune factors and ankylosing spondylitis: insights from a Mendelian Randomization study.}, journal = {Advances in rheumatology (London, England)}, volume = {64}, number = {1}, pages = {89}, pmid = {39696529}, issn = {2523-3106}, mesh = {*Spondylitis, Ankylosing/genetics/immunology ; Humans ; *Mendelian Randomization Analysis ; *Genome-Wide Association Study ; *Monocytes/immunology ; HLA-DR Antigens/genetics ; Lipopolysaccharide Receptors/genetics ; Receptors, IgG/genetics ; Phenotype ; Polymorphism, Single Nucleotide ; Causality ; }, abstract = {BACKGROUND: Despite previous studies indicating a close relationship between immune system and ankylosing spondylitis (AS), the causal relationship between them remains unclear.

METHODS: Genome-wide association data were utilized to explore the causal link between 731 immune cells and AS using a bidirectional two-sample MR approach. The data included immune cell data from Orrù et al.'s study and AS data from the FinnGen consortium. Cochran's Q test and leave-one-out checked instrument variable (IV) heterogeneity. IVW was the primary method for causal analysis, with MR-Egger and MR-PRESSO addressing horizontal pleiotropy. FDR correction was applied to both analysis directions to rectify multiple testing errors.

RESULTS: In our study, 22 immune phenotypes out of 731 were casually linked to AS. After excluding 5 less robust features, 17 immune factors remained, with 4 being protective and the rest posing risks. Through FDR correction, we found a significant causal relationship between HLA DR on CD14- CD16+ monocyte and AS (OR (95%CI) = 0.70(0.60 ~ 0.83), P = 2.06*10[-5]). In the reverse analysis with AS as exposure, potential effects on 34 immune features were discovered. After correction, we confirmed significant causal relationships between AS and two immune features, namely CD20- B cell %lymphocyte (OR (95%CI) = 1.16(1.08-1.25), P = 1.91*10[-5]) and CD20- B cell %B cell (OR (95%CI) = 1.17(1.09-1.26), P = 1.50*10[-5]).

CONCLUSIONS: Our study identified various features associated with AS in different types of immune cells. These findings provide important clues and a theoretical basis for further understanding the pathogenesis of AS, guiding clinical treatment, and drug design.}, } @article {pmid39696263, year = {2024}, author = {Abou-Abbas, L and Sabbagh, D and Rossi, R and Vijayasingham, L and Lteif, MR and Rawi, H and Mitri, R and Al Sultan, H and Benyaich, A and Al-Mosa, A and Truppa, C}, title = {Challenges in accessing health care services for women and girls with disabilities using a humanitarian physical rehabilitation program in Lebanon: a mixed method study.}, journal = {International journal for equity in health}, volume = {23}, number = {1}, pages = {267}, pmid = {39696263}, issn = {1475-9276}, mesh = {Humans ; Lebanon ; *Health Services Accessibility/statistics & numerical data ; Female ; Retrospective Studies ; *Persons with Disabilities/statistics & numerical data ; Adolescent ; Child ; Adult ; Young Adult ; Male ; Healthcare Disparities/statistics & numerical data ; Child, Preschool ; Middle Aged ; Altruism ; Gender Equity ; }, abstract = {BACKGROUND: Achieving equitable healthcare access for persons with disabilities is vital, as they often face various barriers that impact their health and well-being. Recognizing the importance of gender equity, this study aims to explore the specific barriers faced by women and girls with disabilities in accessing quality healthcare services in Lebanon.

METHODS: A mixed-method sequential explanatory approach was employed. Initially, a retrospective descriptive study analyzed data from the International Committee of the Red Cross (ICRC)-supported physical rehabilitation programme (PRP) database. Subsequently, in-depth interviews were conducted to delve into factors influencing gender-disproportionate service users and to uncover barriers to accessing healthcare. Levesque et al.'s 'Conceptual framework on healthcare access' was used to organize and map the results.

RESULTS: The quantitative analysis of service utilization at ICRC PRP centers from 2015 to 2022 revealed significant gender disparities, with males comprising 66.6% of service users compared to 33.4% females. This trend was consistent across age categories, nationalities, and clinical conditions. Healthcare access for women and girls with disabilities was found to be inadequate across all five dimensions of the Levesque framework: adequacy, accessibility, affordability, appropriateness, and availability, as well as their corresponding abilities. While certain challenges such as transportation, financial constraints, inadequate infrastructure, and limited information on available services were common to both genders, gender-specific barriers primarily included societal norms, safety concerns during unaccompanied visits to healthcare facilities, limited access to societal information, economic disparities, preferences for female healthcare providers, and the need for privacy during consultations.

CONCLUSION: This study underscores key barriers hindering healthcare access for women and girls with disabilities in Lebanon, necessitating tailored interventions. Gender-specific challenges, including societal norms and safety concerns, require targeted solutions for improved access and outcomes. This study serves as a call to action for stakeholders at various levels to collaborate and implement concrete measures to bridge the gap in healthcare access and ensure that no one is left behind.}, } @article {pmid39690656, year = {2024}, author = {Ngoc, NPN and Thi, HA and Van Vinh, N}, title = {Exactly solvable dual bus-route model.}, journal = {Physical review. E}, volume = {110}, number = {5-1}, pages = {054130}, doi = {10.1103/PhysRevE.110.054130}, pmid = {39690656}, issn = {2470-0053}, abstract = {In 1998, O'Loan et al. introduced a simplified bus-route model to illustrate bus dynamics. However, fluctuations in passenger numbers make it challenging to achieve an exact solution for the model's stationary state, as these fluctuations can impact bus behavior. In this study, we present an exactly solvable model for a dual bus-route system that builds upon O'Loan et al.'s model. This dual model allows us to comprehensively analyze bus-route dynamics. Our model introduces additional parameters not previously considered by O'Loan et al. to account for neighboring effects and align with an observation in the original model, which can influence the average stationary current and velocity of buses. When the neighboring effect is weak, our model behaves similarly to O'Loan et al.'s bus-route model. However, with a strong neighboring effect, our model exhibits intriguing characteristics. Additionally, in some limiting cases, our model recovers well-known models such as the simple exclusion process, its generalization, the cooperative exclusion process, and the RNA polymerase model during the elongation stage.}, } @article {pmid39690247, year = {2025}, author = {Jiao, XF and Zhang, Z and Gong, L and Lan, S and Zhang, S and Wang, J and Chen, X and Wei, Q and Li, H and Zeng, L and Han, L and Zhang, L}, title = {The quantity, reliability, transparency, reporting, and interpretation of pharmacovigilance signal detection studies in pregnancy: a meta-epidemiological study.}, journal = {European journal of clinical pharmacology}, volume = {81}, number = {2}, pages = {309-319}, pmid = {39690247}, issn = {1432-1041}, support = {2022NSFSC0644//Natural Science Foundation of Sichuan Province/ ; }, mesh = {*Pharmacovigilance ; Humans ; Pregnancy ; Female ; *Adverse Drug Reaction Reporting Systems/standards ; *Drug-Related Side Effects and Adverse Reactions/epidemiology ; Reproducibility of Results ; Pregnancy Complications ; Epidemiologic Studies ; Databases, Factual ; }, abstract = {PURPOSE: To systematically review the characteristics of the available pharmacovigilance signal detection studies in pregnancy, and comprehensively assess the reliability, transparency, reporting, and interpretation of these studies.

METHODS: We searched five databases from inception to February 2024 to identify the available pharmacovigilance signal detection studies in pregnancy. We extracted three aspects of information (basic information, data processing modes, signal detection analyses) to assess the reliability, transparency, and reporting of each study. Moreover, we adopted the criteria of Mouffak et al.'s study to assess the misinterpretation of signal detection results in these studies.

RESULTS: A total of 33 pharmacovigilance signal detection studies in pregnancy were identified. Among them, there were great methodological heterogeneities in the data processing modes (restriction to the population, comparator, standardization of drug names and adverse event names, the assigned roles of drugs, counting unit, etc.) and signal detection analyses (signal detection method, sensitivity analysis, subgroup analysis, adjustment for confounding factors, etc.). Moreover, 13 (39%) studies had at least one type of inappropriate interpretation and/or extrapolation of signal detection results.

CONCLUSION: Our results reveals that the quantity of pharmacovigilance signal detection studies in pregnancy is relatively limited. Furthermore, the reliability, transparency, reporting, and interpretation of the existing studies are less optimistic. The main issues existing in the available pharmacovigilance signal detection studies in pregnancy consist of two aspects: (1) great methodological heterogeneities exist in the data processing modes and signal detection analyses among different studies and (2) inappropriate interpretation and extrapolation of signal detection results are frequent.}, } @article {pmid39685451, year = {2024}, author = {Kim, W and Kim, T and Lee, T}, title = {Experimental Evaluation of Concrete Blended with Eco-Friendly Bio-Sulfur as a Cement Replacement Material.}, journal = {Materials (Basel, Switzerland)}, volume = {17}, number = {23}, pages = {}, pmid = {39685451}, issn = {1996-1944}, support = {G232022017963//the Ministry of Environment (ME, Korea)/ ; }, abstract = {Bio-sulfur (BS), extracted from landfill bio-gas via microbial methods, was examined herein as a potential cement replacement material. The study developed five modified BS variants through limestone incorporation processes (sulfur-to-limestone ratios of 1:0.5, 1:1, 1:1.5, 1:3, and 1:5). The study revealed that modified BS with higher limestone ratios demonstrates significant workability and strength reductions of over 50% with increased content, leading to the adoption of a sulfur-to-limestone ratio of 1:1. The concrete specimens exhibited compressive strength improvements of up to 12% with increased BS content, while the UPV showed proportional increases with increased BS content that remained independent of the water/binder (W/B) ratio. Statistical analysis confirmed significance with p-values below 0.05. XRD analysis identified initial cement hydrate peaks at 3 d that evolved into distinct Mg-S hydrate and Ca-Al-S hydrate formations in the BS-containing specimens by 28 d.}, } @article {pmid39670762, year = {2024}, author = {Uramatsu, M and Andoh, Y and Kojima, T and Mishima, S and Takahashi, M and Uchida, K and Wada, J and Oto, T and Ishikawa, T and Barach, P and Fujisawa, Y}, title = {Five-year analysis of hospital complaints at a Japanese tertiary teaching hospital.}, journal = {International journal for quality in health care : journal of the International Society for Quality in Health Care}, volume = {36}, number = {4}, pages = {}, doi = {10.1093/intqhc/mzae113}, pmid = {39670762}, issn = {1464-3677}, mesh = {Humans ; *Hospitals, Teaching ; *Tertiary Care Centers ; Japan ; *Patient Satisfaction ; Quality of Health Care ; Quality Improvement ; East Asian People ; }, abstract = {BACKGROUND: Patient complaint taxonomies strongly support the use of healthcare complaints as a powerful tool to improve the quality and safety of patient care. Hospitals use complaint data at the organizational level to address quality variation across service lines and departments.

METHODS: We applied a validated typology method to identify where the complaints occured and gained deeper insights about how they can be more effectively utilized to drive and implement continuous quality and service improvement activities within a tertiary hospital. We included all complaints and opinions from patients and their families over a 5-year period at a large tertiary teaching hospital in Japan. Two analysts categorized the opinions into complaints and gratitude expressions, with complaints classified using Reader et al.'s taxonomy. We performed statistical tabulations and determined the number of complaints across hospital sectors using the chi-squared test, residual analysis, and Cramer's V tests to check for significant correlations between the variables.

RESULTS: A total of 6607 complaints and comments were received. Of these, 5401 related to the Clinical, Administrative, and Human Relations domains, respectively (11.1%, 56.1%, and 32.8%). At the domain level, the most common complaints are related to the Relationships domain in both the Medical and Nursing departments. However, a detailed analysis of the category levels demonstrated that the Medicine department received the most complaints in the Communication and Patient Rights category, whereas in the Nursing department, the Humanness/Caring and Patient Rights categories were the most common sources for complaints. The Administrative department complaints were mostly related to the Management domain, with the largest number of complaints related to the Institutional Issues category.

CONCLUSIONS: We used a validated taxonomy to identify and address trends in patient complaints and identified the key hospital departments that required remedial improvement actions. All hospital departments received direct and targeted feedback on how to effectively improve the quality, safety and services of their clinical service lines.}, } @article {pmid39667988, year = {2025}, author = {Miler, K}, title = {Ethanol and pollinators: expanding Bowland et al.'s framework.}, journal = {Trends in ecology & evolution}, volume = {40}, number = {2}, pages = {115-116}, doi = {10.1016/j.tree.2024.11.019}, pmid = {39667988}, issn = {1872-8383}, } @article {pmid39666494, year = {2025}, author = {Marx, BP and Sloan, DM and Keane, TM and Pollack, S and Schnurr, PP}, title = {Veterans health administration leads the way in population mental health science: Commentary on Dodge et al. (2024).}, journal = {The American psychologist}, volume = {80}, number = {2}, pages = {279-281}, doi = {10.1037/amp0001428}, pmid = {39666494}, issn = {1935-990X}, mesh = {Humans ; United States ; *United States Department of Veterans Affairs ; *Mental Health Services/organization & administration ; *Mental Health ; *Veterans/psychology ; }, abstract = {Recently, Dodge et al. (2024) published an article in American Psychologist offering recommendations to the mental health field for changing from an individual-level to a population-level focus. These recommendations included scaling up evidence-based programs, innovating and evaluating population-level interventions, and creating a primary system of care to promote mental health and well-being. For the past 2 decades, the Veterans Health Administration has been successfully engaged in these activities. In this commentary, we describe some of these ongoing efforts to demonstrate that Dodge et al.'s (2024) recommendations are indeed feasible with the proper infrastructure and resources and that the Veterans Health Administration's efforts can serve as a model for the field. (PsycInfo Database Record (c) 2025 APA, all rights reserved).}, } @article {pmid39657971, year = {2025}, author = {Solum, S and Salbaş, E}, title = {Validity and Reliability of the Turkish Version of the Low Back Activity Confidence Scale (LoBACS).}, journal = {Evaluation & the health professions}, volume = {48}, number = {3}, pages = {347-354}, doi = {10.1177/01632787241307031}, pmid = {39657971}, issn = {1552-3918}, mesh = {Reproducibility of Results ; Humans ; Translations ; Turkey ; Language ; *Low Back Pain/diagnosis/psychology ; *Self Concept ; Factor Analysis, Statistical ; Male ; Female ; Adolescent ; Young Adult ; Adult ; Middle Aged ; Aged ; Disability Evaluation ; *Surveys and Questionnaires/standards ; *Pain Measurement/methods/psychology/statistics & numerical data ; Psychometrics ; }, abstract = {The Low Back Activity Confidence Scale (LoBACS) is a 15-item scale designed to assess low back pain (LBP) through self-efficacy, a key predictor of functional recovery. This study aimed to culturally adapt and evaluate the validity and reliability of the Turkish version of LoBACS in patients with LBP. The translation and adaptation followed Beaton et al.'s protocol. Content and face validity were assessed with a pre-patient group. Both exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were performed to evaluate construct validity. Internal consistency, as well as test-retest reliability, were evaluated in a sample of 150 patients aged 18-70 years. Concurrent validity was measured alongside the Oswestry Back Pain Disability Questionnaire (ODQ) and Quebec Back Pain Disability Scale (QBPDS). Two factors emerged from factor analysis, with item loadings for Functional Self-efficacy (FnSE) ranging from 0.745 to 0.896 and for Self-Regulatory and Exercise Self-efficacy (Self-Reg&ExSE) from 0.817 to 0.940. Cronbach's alpha was high for FnSE, Self-Reg&ExSE, and the total scale (α = 0.941). Total correlation for each item ranged between 0.770 and 0.925. Test-retest reliability was also high (r = 0.941, p < .01). LoBACS showed moderate agreement with ODQ and QBPDS, demonstrating concurrent validity. In conclusion, the Turkish version of LoBACS is a valid and reliable tool for measuring LBP-related self-efficacy.}, } @article {pmid39657546, year = {2025}, author = {Stüber, AT and Heimer, MM and Ta, J and Fabritius, MP and Hoppe, BF and Sheikh, G and Brendel, M and Unterrainer, L and Jurmeister, P and Tufman, A and Ricke, J and Cyran, CC and Ingrisch, M}, title = {Replication study of PD-L1 status prediction in NSCLC using PET/CT radiomics.}, journal = {European journal of radiology}, volume = {183}, number = {}, pages = {111825}, doi = {10.1016/j.ejrad.2024.111825}, pmid = {39657546}, issn = {1872-7727}, mesh = {Humans ; *Carcinoma, Non-Small-Cell Lung/diagnostic imaging/metabolism ; *Lung Neoplasms/diagnostic imaging/metabolism ; *Positron Emission Tomography Computed Tomography/methods/statistics & numerical data ; Female ; Male ; Middle Aged ; *B7-H1 Antigen/metabolism ; Reproducibility of Results ; Aged ; Sensitivity and Specificity ; Biomarkers, Tumor/metabolism ; Machine Learning ; Radiopharmaceuticals ; Fluorodeoxyglucose F18 ; Aged, 80 and over ; Adult ; Radiomics ; }, abstract = {This study investigates the predictive capability of radiomics in determining programmed cell death ligand 1 (PD-L1) expression (>=1%) status in non-small cell lung cancer (NSCLC) patients using a newly collected [18F]FDG PET/CT dataset. We aimed to replicate and validate the radiomics-based machine learning (ML) model proposed by Zhao et al. [1] predicting PD-L1 status from PET/CT-imaging. An independent cohort of 254 NSCLC patients underwent [18F]FDG PET/CT imaging, with primary tumor segmentation conducted using lung tissue window (LTW) and more conservative soft tissue window (STW) methods. Radiomics models ("Rad-score" and "complex model") and a clinical-stage model from Zhao et al. were evaluated via 10-fold cross-validation and AUC analysis, alongside a benchmark-study comparing different ML-model pipelines. Clinicopathological data were collected from medical records. On our data, the Rad-score model yielded mean AUCs of 0.593 (STW) and 0.573 (LTW), below Zhao et al.'s 0.761. The complex model achieved mean AUCs of 0.505 (STW) and 0.519 (LTW), lower than Zhao et al.'s 0.769. The clinical model showed a mean AUC of 0.555, below Zhao et al.'s 0.64. All models performed significantly lower than Zhao et al.'s findings. Our benchmark study on four ML pipelines revealed consistently low performance across all configurations. Our study failed to replicate original findings, suggesting poor model performance and questioning predictive value of radiomics features in classifying PD-L1 expression from PET/CT imaging. These results highlight challenges in replicating radiomics-based ML models and stress the need for rigorous validation.}, } @article {pmid39654263, year = {2025}, author = {Beck, V and Brooks, JL and Stephens, R}, title = {The effect of swearing on error-related negativity as an indicator for state disinhibition.}, journal = {Quarterly journal of experimental psychology (2006)}, volume = {}, number = {}, pages = {17470218241308560}, doi = {10.1177/17470218241308560}, pmid = {39654263}, issn = {1747-0226}, abstract = {Swearing has been linked to increased strength performance, and state disinhibition may be the mechanism linking swearing and strength. Error-related negativity (ERN) is a neural signal associated with response monitoring. Its reduction has been proposed as neural marker for state disinhibition, and therefore, we predicted that swearing would lead to a decreased ERN compared with neutral word repetition, indicating state disinhibition. The study (N = 52) used a within-subjects experimental design with two conditions. Participants repeated either a swear or neutral word aloud for 10 s before engaging in an arrowhead flanker task, a grip strength task, and several questionnaires. ERN was measured continually using electroencephalography (EEG). The study replicated previously found effects of swearing on strength, humour, positive emotion, and distraction. In addition, swearing was found to have a significant effect on state behavioural activation (BAS drive). However, results indicated no significant difference between conditions on ERN amplitude. This pre-registered study has confirmed that, relative to a neutral word, repeating a swear word leads to increased performance on a grip strength task while also confirming effects of swearing on positive emotion, humour, and distraction. Its novel contribution is confirming that swearing raises state behavioural activation. This supports application of Hirsh et al.'s state disinhibition theory to swearing to some extent, although the absence of any effect of swearing on ERN limits this interpretation.}, } @article {pmid39648359, year = {2025}, author = {Lagacé, MB and Lachance-Grzela, M and Ross-Plourde, M and Brassard, A}, title = {The explanatory role of psychological distress in the link between role blurring and relationship satisfaction: A dyadic study.}, journal = {Journal of marital and family therapy}, volume = {51}, number = {1}, pages = {e12753}, pmid = {39648359}, issn = {1752-0606}, support = {//Faculty of Research and Graduate Studies at Moncton University/ ; }, mesh = {Humans ; Female ; Adult ; *Personal Satisfaction ; *Psychological Distress ; Male ; *Interpersonal Relations ; Middle Aged ; Spouses/psychology ; Canada ; Young Adult ; Surveys and Questionnaires ; }, abstract = {Role blurring has been associated with negative outcomes, such as anxiety and stress. Paulin et al.'s study found that role blurring is linked to lower relationship satisfaction through higher psychological distress. However, this link has not been explored from a dyadic perspective, neglecting the interrelation between partners in a couple. The current study aimed to address this limitation by examining the explanatory role of psychological distress in the link between role blurring and relationship satisfaction from a dyadic perspective. The sample comprised 382 Canadian participants (191 couples) over 18 years old who answered online questionnaires through the SurveyMonkey platform. The results showed that women's life-work role blurring is negatively associated with their own and their partner's relationship satisfaction through their own more significant psychological distress. These findings underscore the importance of researchers further investigating life-work role blurring in the future from a dyadic perspective.}, } @article {pmid39647137, year = {2024}, author = {Fitzhugh, K and Mortimer, K and Brasil, ACDS}, title = {The monophyly of Magelona F. Müller, 1858 (Polychaeta, Magelonidae): Comments on Meißner et al.'s (2023) reinstatement of Octomagelona Aguirrezabalaga, Ceberio & Fiege, 2001.}, journal = {Zootaxa}, volume = {5497}, number = {4}, pages = {496-504}, doi = {10.11646/zootaxa.5497.4.2}, pmid = {39647137}, issn = {1175-5334}, mesh = {Animals ; *Polychaeta/classification/anatomy & histology ; *Phylogeny ; Animal Distribution ; }, abstract = {The first published phylogenetic hypotheses involving members of the polychaete taxon Magelonidae Cunningham & Ramage, 1888, were reported by Mortimer et al. (2021), wherein results showed that for the two genera in the family, Magelona F. Müller, 1858, was paraphyletic relative to Octomagelona Aguirrezabalaga, Ceberio & Fiege, 2001. The only option to formally name at least some of the resultant phylogenetic hypotheses was to place Octomagelona into synonymy with Magelona, leaving the definition of Magelonidae redundant with that of a monophyletic Magelona. Meißner et al. (2023) subsequently described specimens as members of new species, Octomagelona borowskii Fiege, Knebelsberger & Meißner, 2023, and O. sp. cf. O. borowskii, with the view that Octomagelona should be maintained as distinct from Magelona. We present reasons why reestablishing the paraphyly of Magelona is scientifically unwarranted.}, } @article {pmid39644513, year = {2025}, author = {Varasteh, S and Nia, HS and Navidhamidi, M and Esmaeili, M}, title = {Explaining the Concept of Moral Resilience in Intensive Care Unit Nurses: A Directed Content Analysis.}, journal = {Nursing inquiry}, volume = {32}, number = {1}, pages = {e12692}, doi = {10.1111/nin.12692}, pmid = {39644513}, issn = {1440-1800}, support = {//This work was supported by the Tehran University of Medical Sciences and Health Services./ ; }, mesh = {Humans ; *Resilience, Psychological ; *Intensive Care Units/organization & administration ; *Qualitative Research ; Female ; Adult ; *Morals ; Male ; Nursing Staff, Hospital/psychology ; Critical Care Nursing/standards ; Interviews as Topic/methods ; Middle Aged ; }, abstract = {Moral resilience is an emerging concept that has not been fully acknowledged. The aim of this study is to explain lived experiences of moral resilience in intensive care units nurses. This is a qualitative study with a content analysis approach guided by the method of Elo and Kyngäs and based on the theoretical framework of Defilippis et al. Data were collected through 17 in-depth, individual, and semi-structured interviews with 17 nurses, who were selected by purposeful sampling. The results of the present study support the theory of Defilippis et al. while adding another category to it. Three categories of self-awareness, harmonized connection, and moral well-being, which are consistent with the result of Defilippis et al. were extracted deductively, while the category of moral agency was also extracted inductively from the data. The explanatory theory resulting from Defilippis et al.'s study can be used as a guide to cultivate and improve the moral resilience of nurses working in intensive care units. Moral resilience is fostered in nurses by nurturing and improving their capacities, such as self-awareness, self-efficacy, self-confidence, and self-reflection. These traits can help maintain and promote moral agency while establishing harmonized connections. Acquiring moral resilience skills can lead to positive outcomes and reduced moral distress.}, } @article {pmid39644171, year = {2025}, author = {Andrews, JL and Foulkes, L}, title = {Debate: Where to next for universal school-based mental health interventions? Time to move towards more effective alternatives.}, journal = {Child and adolescent mental health}, volume = {30}, number = {1}, pages = {102-104}, pmid = {39644171}, issn = {1475-357X}, support = {/WT_/Wellcome Trust/United Kingdom ; CQR02370//Prudence Trust/ ; WT/227640/Z/23/Z//Wellcome/ ; }, mesh = {Humans ; Adolescent ; *Mental Disorders/prevention & control ; *School Mental Health Services ; }, abstract = {There is an urgent need to improve mental health outcomes among young people. One approach taken to address this problem has been the design and delivery of universal school-based prevention, based on therapeutic models such as CBT and mindfulness. Such interventions are delivered to groups of young people, irrespective of risk or need. However, in this commentary, we argue that the initial appeal of universal interventions has not been supported by the evidence: universal school-based prevention is less effective than targeted approaches, often leads to null or unsustained positive effects, has the potential to elicit negative effects and is not well liked by young people themselves. In addition, many young people in each classroom already meet the criteria for a mental disorder, meaning that prevention approaches may not be appropriate or effective for this group. In this commentary, we respond to Birrell et al.'s (2025) paper by arguing that the field should move away from universal prevention and instead invest our limited resources in the refinement and dissemination of interventions with a stronger evidence base, such as one-to-one, targeted and indirect approaches.}, } @article {pmid39630638, year = {2025}, author = {Hauenstein, CE and Thomas, RP and Illingworth, DA and Dougherty, MR}, title = {Rethinking the Role of Teams and Training in Geopolitical Forecasting: The Effect of Uncontrolled Method Variance on Statistical Conclusions.}, journal = {Psychological science}, volume = {36}, number = {1}, pages = {3-18}, doi = {10.1177/09567976241266481}, pmid = {39630638}, issn = {1467-9280}, mesh = {Humans ; Forecasting/methods ; Male ; Female ; Adult ; Young Adult ; *Group Processes ; }, abstract = {Using data from a geopolitical forecasting tournament, Mellers et al. (2014) [Psychological strategies for winning a geopolitical forecasting tournament. Psychological Science, 25, 1106-1115] concluded that forecasting ability was improved by allowing participants to work in teams and providing them with probability training. Here, we reevaluated Mellers et al.'s conclusions using an item response theory framework that models latent ability from forecasting choices. We found that the relationship between latent ability estimates and forecast accuracy differed from the interpretation of the original findings once key extraneous variables were statistically controlled. The best fit models across the first 2 years of the tournament included one or more extraneous variables that substantially eliminated, reduced, and, in some cases, even reversed the effects of the experimental manipulations of teaming and training on latent forecasting ability. We also show that latent traits associated with strategic responding can discriminate between superforecasters and non-superforecasters, making it difficult to identify the latent factors that underlie the superforecasters' superior performance.}, } @article {pmid39628859, year = {2024}, author = {Chen, R and Lin, T and Liu, L and Liu, J and Chen, R and Zou, J and Liu, C and Natarajan, L and Tang, W and Zhang, X and Tu, X}, title = {A doubly robust estimator for the Mann Whitney Wilcoxon rank sum test when applied for causal inference in observational studies.}, journal = {Journal of applied statistics}, volume = {51}, number = {16}, pages = {3267-3291}, pmid = {39628859}, issn = {0266-4763}, abstract = {The Mann-Whitney-Wilcoxon rank sum test (MWWRST) is a widely used method for comparing two treatment groups in randomized control trials, particularly when dealing with highly skewed data. However, when applied to observational study data, the MWWRST often yields invalid results for causal inference. To address this limitation, Wu et al. (Causal inference for Mann-Whitney-Wilcoxon rank sum and other nonparametric statistics, Stat. Med. 33 (2014), pp. 1261-1271) introduced an approach that incorporates inverse probability weighting (IPW) into this rank-based statistic to mitigate confounding effects. Subsequently, Mao (On causal estimation using U-statistics, Biometrika 105 (2018), pp. 215-220), Zhang et al. (Estimating Mann Whitney-type causal effects, J. Causal Inference 7 (2019), ARTICLE ID 20180010), and Ai et al. (A Mann-Whitney test of distributional effects in a multivalued treatment, J. Stat. Plan. Inference 209 (2020), pp. 85-100) extended this IPW estimator to develop doubly robust estimators. Nevertheless, each of these approaches has notable limitations. Mao's method imposes stringent assumptions that may not align with real-world study data. Zhang et al.'s (Estimating Mann Whitney-type causal effects, J. Causal Inference 7 (2019), ARTICLE ID 20180010) estimators rely on bootstrap inference, which suffers from computational inefficiency and lacks known asymptotic properties. Meanwhile, Ai et al. (A Mann-Whitney test of distributional effects in a multivalued treatment, J. Stat. Plan. Inference 209 (2020), pp. 85-100) primarily focus on testing the null hypothesis of equal distributions between two groups, which is a more stringent assumption that may not be well-suited to the primary practical application of MWWRST. In this paper, we aim to address these limitations by leveraging functional response models (FRM) to develop doubly robust estimators. We demonstrate the performance of our proposed approach using both simulated and real study data.}, } @article {pmid39623427, year = {2024}, author = {Chamut, S and Alhassan, M and Hameedaldeen, A and Kaplish, S and Yang, AH and Wade, CG and Alghamdi, S and Chamut, D and Novy, BB and Chandel, T}, title = {Every bite counts to achieve oral health: a scoping review on diet and oral health preventive practices.}, journal = {International journal for equity in health}, volume = {23}, number = {1}, pages = {261}, pmid = {39623427}, issn = {1475-9276}, mesh = {Humans ; *Oral Health/standards ; *Dental Caries/prevention & control ; *Diet/standards ; Oral Hygiene/methods ; Health Behavior ; Social Determinants of Health ; }, abstract = {OBJECTIVE: To examine the landscape of preventive strategies and interventions directed to achieve oral health equity, with particular emphasis on the interplay between dental caries prevention, individual behaviors, and population-level strategies across various demographic and geographic regions.

METHODS: This scoping review was guided by Peters et al.'s framework, which incorporates four key concepts aimed at reducing caries: education for individuals and healthcare providers, behavioral modifications, addressing broader social determinants of health, and extending oral health education programs beyond traditional dental settings. A systematic search was conducted across five databases, from 2011 to 2022.

RESULTS: This review identified 107 studies highlighting three main themes: behavioral practices (N = 33), which focused on reducing the prevalence of caries, improving oral hygiene practices, and enhancing overall oral health knowledge; educational interventions (N = 39), which explored strategies to integrate oral health with broader public health initiatives; and dietary interventions (N = 35), which emphasized the critical relationship between diet and oral health.

CONCLUSION: This SR highlights the critical need for comprehensive multilevel approaches that address the complex interplay between nutrition, oral health, and sociodemographic factors, while emphasizing the critical relationship between societal factors and individual health behaviors. Multifaceted interventions that include behavioral change, education, and dietary modifications are crucial for improving oral and overall health outcomes across diverse populations. Comprehensive strategies should prioritize medical-dental integration and data-driven approaches to effectively reduce oral health disparities for vulnerable populations, promoting long-term health equity.}, } @article {pmid39621188, year = {2025}, author = {Gerometta, M and Henderson, RD and Friend, R and Cooper, LT and Zhao, J and Boyd, AW and Bartlett, PF}, title = {Evaluation of NUN-004, a Novel Engineered Ephrin Antagonist, in Healthy Volunteers and Patients with Amyotrophic Lateral Sclerosis: A Phase I/Ib, Open-Label, Escalating Dose and Extended Access Study.}, journal = {Clinical drug investigation}, volume = {45}, number = {1}, pages = {17-28}, pmid = {39621188}, issn = {1179-1918}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy ; Male ; Female ; Middle Aged ; Adult ; Dose-Response Relationship, Drug ; Aged ; Healthy Volunteers ; *Receptor, EphA4/antagonists & inhibitors ; Half-Life ; Young Adult ; *Recombinant Fusion Proteins/pharmacokinetics/adverse effects/administration & dosage/therapeutic use ; }, abstract = {BACKGROUND: Erythropoietin-producing hepatocellular carcinoma A4 (EphA4) is implicated in the pathophysiology of amyotrophic lateral sclerosis. EphA4 fusion protein (EphA4-Fc) inhibits EphA4 function in vivo but is too short-lived for prolonged therapy. NUN-004 (mEphA4-Fc) is a modified EphA4-Fc engineered for an extended half-life.

OBJECTIVE: This first-in-human phase I/Ib study evaluated the safety, tolerability, pharmacokinetics, immunogenicity and efficacy of NUN-004 in healthy volunteers and patients with amyotrophic lateral sclerosis.

METHODS: In this open-label study, Part 1 enrolled 20 healthy volunteers in five single ascending dose cohorts (1, 3, 10, 20 and 30 mg/kg), followed by Part 2, which enrolled eight patients with amyotrophic lateral sclerosis in two multiple ascending dose cohorts (cycle 1: 15 and 30 mg/kg) who could continue into an extended access phase (cycles 2-6: 15 mg/kg) for a total of 6 months' treatment. All participants received intravenous NUN-004; multiple dosing was administered weekly in 28-day cycles. Primary endpoints included safety assessments, single-dose and multiple-dose pharmacokinetics, and anti-drug antibodies. Efficacy assessments were Amyotrophic Lateral Sclerosis Function Rating Score Revised (ALSFRS-R) and forced vital capacity.

RESULTS: NUN-004 was well tolerated, with no serious adverse events or discontinuations. NUN-004 exposure generally increased with dose. Single-dose half-life was 111.7 (± 22.8) h in healthy volunteers (n = 20) and 74.4 (± 19.4) h in patients (n = 6). Steady state was observed in patients by day 8. Steady-state half-life (cycle 1 doses 2-4) was 83.7 (± 26.6) to 101.1 (± 46.0) h. No antibody response was observed. ALSFRS-R showed a slight improvement (+0.09 points/month) to cycle 4 and a slight decline (-0.35 points/month) over the whole study. Forced vital capacity trends were consistent with ALSFRS-R.

CONCLUSIONS: This study supports the safety, tolerability and extended half-life of NUN-004, and provides preliminary evidence for its ability to ameliorate disease progression in an amyotrophic lateral sclerosis cohort.

CLINICAL TRIAL REGISTRATION: Registered on ANZCTR under identifier ACTRN12621000514808 (3 May, 2021).}, } @article {pmid39617962, year = {2025}, author = {Hervik, SEK and Hervik, AK and Thoresen, T and Thurston, M}, title = {"When you've been living in darkness, the light suddenly becomes frightening" - prisoners' experiences of health promotion in a Norwegian prison.}, journal = {International journal of prison health}, volume = {21}, number = {1}, pages = {42-54}, doi = {10.1108/IJOPH-05-2024-0026}, pmid = {39617962}, issn = {2977-0262}, mesh = {Humans ; Male ; Norway ; *Prisoners/psychology ; *Health Promotion/organization & administration ; Adult ; *Prisons/organization & administration ; Qualitative Research ; Middle Aged ; Interviews as Topic ; }, abstract = {PURPOSE: A settings-based approach to health promotion emphasizes everyday environments in shaping health. Prisons are, therefore, potentially important arenas for health promotion. However, the inherent restriction of prisoner agency presents a fundamental challenge in this regard. There is a gap in qualitative research on prisoners' perspectives on health-related topics and a need for greater understanding of health promotion within prisons. This study aims to explore male prisoners' experiences of a Norwegian low-security prison as a setting for health promotion.

DESIGN/METHODOLOGY/APPROACH: This study was conducted in Forest Prison, a Norwegian low-security facility for 125 male prisoners. The prison offers various amenities and activities to prepare inmates for reintegration into society. The research used semi-structured interviews with 20 diverse prisoners. Interviews were transcribed and analyzed using Gale et al.'s framework method.

FINDINGS: This study revealed varied prisoner perspectives on Forest Prison as a setting for health promotion. In prisoners' talk, the importance of agency was evident. Restricted agency triggered negative emotions and distrust, while extended agency fostered trust and wellbeing. Although Forest Prison provides a considerable degree of agency, some prisoners did not fully benefit from this agentic context because of disparities in resources.

ORIGINALITY/VALUE: Initiatives across three areas of action will strengthen Forest Prison as a setting for health promotion: extending agency, empowering prisoners and developing a prison culture with positive social relationships, effective communication and information flow. The findings of this study provide theoretical insights beyond the specific context, which can serve as a basis for developing prisons as health promoting settings.}, } @article {pmid39616821, year = {2025}, author = {Norris, D and McQueen, JM}, title = {Why might there be lexical-prelexical feedback in speech recognition?.}, journal = {Cognition}, volume = {255}, number = {}, pages = {106025}, doi = {10.1016/j.cognition.2024.106025}, pmid = {39616821}, issn = {1873-7838}, mesh = {Humans ; *Speech Perception/physiology ; *Recognition, Psychology/physiology ; Feedback, Psychological/physiology ; Speech/physiology ; Psycholinguistics ; }, abstract = {In reply to Magnuson, Crinnion, Luthra, Gaston, and Grubb (2023), we challenge their conclusion that on-line activation feedback improves word recognition. This type of feedback is instantiated in the TRACE model (McClelland & Elman, 1986) as top-down spread of activation from lexical to phoneme nodes. We give two main reasons why Magnuson et al.'s demonstration that activation feedback speeds up word recognition in TRACE is not informative about whether activation feedback helps humans recognize words. First, the same speed-up could be achieved by changing other parameters in TRACE. Second, more fundamentally, there is room for improvement in TRACE's performance only because the model, unlike Bayesian models, is suboptimal. We also challenge Magnuson et al.'s claim that the available empirical data support activation feedback. The data they base this claim on are open to alternative explanations and there are data against activation feedback that they do not discuss. We argue, therefore, that there are no computational or empirical grounds to conclude that activation feedback benefits human spoken-word recognition and indeed no theoretical grounds why activation feedback would exist. Other types of feedback, for example feedback to support perceptual learning, likely do exist, precisely because they can help listeners recognize words.}, } @article {pmid39615954, year = {2024}, author = {Murphy, BA and Hall, JA}, title = {How a strong measurement validity review can go astray: A look at and recommendations for future measurement-focused reviews.}, journal = {Clinical psychology review}, volume = {114}, number = {}, pages = {102506}, doi = {10.1016/j.cpr.2024.102506}, pmid = {39615954}, issn = {1873-7811}, mesh = {Humans ; *Psychometrics/standards ; Reproducibility of Results ; }, abstract = {Critical reviews of a test's measurement validity are valuable scientific contributions, yet even strong reviews can be undermined by subtle problems in how evidence is compiled and presented to readers. First, if discussions of poor reporting practices by a test's users are interwoven with discussions about validity support for the test itself, readers can be inadvertently misled into impressions of the latter which are improperly conflated with the former. Second, test reviewers should give at least as much careful attention to a test's external validity as to its structural validity; test reviewers who prioritize factor analysis and internal consistency at the expense of discriminant and convergent validity can inadvertently mislead readers into perceptions of a test which are more negative or more positive than is warranted by the evidence overall. In this commentary, we aim to help test evaluators in crafting critical investigations of measurement validity. We use Higgins et al.'s (2024) review of the Reading the Mind in the Eyes Test (RMET; Baron-Cohen et al., 2001) as a basis for discussion. We argue that their otherwise impressive review went astray in the two ways described above. After considering both the psychometric evidence that Higgins et al. (2024) provided and the external validity evidence that they did not provide, we conclude that their recommendations that the RMET should be abandoned, and that most prior research findings based on it should be reassessed or disregarded, are unwarranted.}, } @article {pmid39614750, year = {2024}, author = {George, DN and Dwyer, DM and Haselgrove, M and Le Pelley, ME}, title = {Apparent statistical inference in crows may reflect simple reinforcement learning.}, journal = {Quarterly journal of experimental psychology (2006)}, volume = {}, number = {}, pages = {17470218241305622}, doi = {10.1177/17470218241305622}, pmid = {39614750}, issn = {1747-0226}, abstract = {Johnston et al. report results which they argue demonstrate that crows engage in statistical inference during decision-making. They trained two crows to associate a set of stimuli with different reward probabilities (from 10% to 90%) before choice tests between pairs of stimuli. Across most pairwise combinations, and in a control task in which the number of rewards was equated between probabilities, both crows preferred the stimulus associated with higher reward probability. The magnitude of this preference was affected by the absolute difference between the two probabilities, although (contrary to a claim made by Johnston et al. 2023) preference did not reflect the ratio of prior probabilities independently of absolute differences. Johnston et al. argue that preference for the stimulus with the higher reward probability is "the signature of true statistical inference" (p. 3238), implemented by an analogue magnitude system that represents the reward probability associated with each stimulus. Here, we show that a simple reinforcement learning model, with no explicit representation of reward probabilities, reproduces the critical features of crows' performance-and indeed better accounts for the observed empirical findings than the concept of statistical inference based on analogue magnitude representations, because it correctly predicts the absence of a ratio effect that would reflect magnitudes when absolute distance is controlled. Contrary to Johnston et al.'s claims, these patterns of behaviour do not necessitate retrieval of calculated reward probabilities from long-term memory and dynamic application of this information across contexts, or (more specifically) require the involvement of an analogue magnitude system in representing abstract probabilities.}, } @article {pmid39610604, year = {2024}, author = {Alhazmi, AY and Faqih, SN and Alsalem, BS and Alsalem, MS and Alnoman, H}, title = {Plastic Surgeons' Attitudes and Understanding of Body Dysmorphic Disorder.}, journal = {Cureus}, volume = {16}, number = {10}, pages = {e72630}, pmid = {39610604}, issn = {2168-8184}, abstract = {Introduction Body dysmorphic disorder (BDD) involves an intense preoccupation with perceived or minor defects in physical appearance. Patients with BDD often experience dissatisfaction across various domains, including mental and physical well-being, relationships, and role functioning. Purpose This study evaluated the awareness, knowledge, and attitudes of plastic surgeons in Saudi Arabia toward BDD. Participants and methods This was a cross-sectional study that included board-certified plastic surgeons in Saudi Arabia. The data was collected through a self-administered survey from July 2022 until May 2023. The total number of participants was 213. The survey includes questions about demographic data, familiarity with BDD, and participant's attitudes toward BDD. The questionnaire was adapted from Bouman et al.'s study. Results Most of the participants were familiar with the clinical picture of BDD; 46.9% were reasonably familiar with the clinical picture of BDD, and 11.3% were totally familiar with the diagnosis. Furthermore, the most common symptoms frequently seen in patients with BDD were "dissatisfaction with previous cosmetic surgery" (68.5%) and "unusual/excessive requests for cosmetic surgery" (67.6%). However, only 21.1% of participants will consult a psychiatrist/psychologist about what to do before proceeding to a cosmetic procedure. Notably, the potential verbal and physical aggression encountered by our participants was 85% among patients with BDD. Conclusion This research demonstrated that plastic surgeons exhibit a high familiarity with BDD. Also, the findings of the current study could be valuable in shaping policies and providing recommendations to assist plastic surgeons and cosmetic treatment institutes in managing BDD patients. Subsequently, a significant proportion of our participants reported receiving threats from BDD patients. Therefore, this highlights the need to explore the risk of post-surgery violence in individuals with BDD.}, } @article {pmid39606487, year = {2024}, author = {Depuydt, L and Renders, L and Van de Vyver, S and Veys, L and Gagie, T and Fostier, J}, title = {b-move: Faster Lossless Approximate Pattern Matching in a Run-Length Compressed Index.}, journal = {Research square}, volume = {}, number = {}, pages = {}, pmid = {39606487}, issn = {2693-5015}, support = {R01 HG011392/HG/NHGRI NIH HHS/United States ; }, abstract = {BACKGROUND: Due to the increasing availability of high-quality genome sequences, pan-genomes are gradually replacing single consensus reference genomes in many bioinformatics pipelines to better capture genetic diversity. Traditional bioinformatics tools using the FM-index face memory limitations with such large genome collections. Recent advancements in run-length compressed indices like Gagie et al.'s r-index and Nishimoto and Tabei's move structure, alleviate memory constraints but focus primarily on backward search for MEM-finding. Arakawa et al.'s br-index initiates complete approximate pattern matching using bidirectional search in run-length compressed space, but with significant computational overhead due to complex memory access patterns.

RESULTS: We introduce b-move, a novel bidirectional extension of the move structure, enabling fast, cache-efficient, lossless approximate pattern matching in run-length compressed space. It achieves bidirectional character extensions up to 7 times faster than the br-index, closing the performance gap with FM-index-based alternatives. For locating occurrences, b-move performs ϕ and ϕ - 1 operations up to 7 times faster than the br-index. At the same time, it maintains the favorable memory characteristics of the br-index, for example, all available complete E. coli genomes on NCBI's RefSeq collection can be compiled into a b-move index that fits into the RAM of a typical laptop.

CONCLUSIONS: b-move proves practical and scalable for pan-genome indexing and querying. We provide a C++ implementation of b-move, supporting efficient lossless approximate pattern matching including locate functionality, available at https://github.com/biointec/b-move under the AGPL-3.0 license.}, } @article {pmid39604072, year = {2025}, author = {Stone, BM and Thrul, J}, title = {Commentary on Serre et al. : Demonstrating the next era of addiction science.}, journal = {Addiction (Abingdon, England)}, volume = {120}, number = {1}, pages = {59-60}, pmid = {39604072}, issn = {1360-0443}, support = {F32 DA061600/DA/NIDA NIH HHS/United States ; T32 DA007292/DA/NIDA NIH HHS/United States ; F32DA061600;T32DA007292/DA/NIDA NIH HHS/United States ; F32DA061600;T32DA007292/DA/NIDA NIH HHS/United States ; }, abstract = {Innovative real-time data collection methodologies, including ecological momentary assessments, allow researchers to apply cutting-edge analytical tools, such as network analyses—unlocking insights that reshape our understanding of substance use and behavioral addictions. Serre et al.’s study epitomizes these innovative approaches poised to advance addiction research.}, } @article {pmid39601384, year = {2025}, author = {Wei, LC and Chiu, HJ}, title = {Reconsidering the Genetic Overlap Between Cognition and Bipolar Disorder: A Commentary on D'Amico et al.'s Family Study.}, journal = {American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics}, volume = {198}, number = {3}, pages = {e33017}, doi = {10.1002/ajmg.b.33017}, pmid = {39601384}, issn = {1552-485X}, } @article {pmid39589160, year = {2025}, author = {Wang, Y and Li, D and Xu, K and Wang, G and Zhang, F}, title = {Copper homeostasis and neurodegenerative diseases.}, journal = {Neural regeneration research}, volume = {20}, number = {11}, pages = {3124-3143}, pmid = {39589160}, issn = {1673-5374}, abstract = {Copper, one of the most prolific transition metals in the body, is required for normal brain physiological activity and allows various functions to work normally through its range of concentrations. Copper homeostasis is meticulously maintained through a complex network of copper-dependent proteins, including copper transporters (CTR1 and CTR2), the two copper ion transporters the Cu -transporting ATPase 1 (ATP7A) and Cu-transporting beta (ATP7B), and the three copper chaperones ATOX1, CCS, and COX17. Disruptions in copper homeostasis can lead to either the deficiency or accumulation of copper in brain tissue. Emerging evidence suggests that abnormal copper metabolism or copper binding to various proteins, including ceruloplasmin and metallothionein, is involved in the pathogenesis of neurodegenerative disorders. However, the exact mechanisms underlying these processes are not known. Copper is a potent oxidant that increases reactive oxygen species production and promotes oxidative stress. Elevated reactive oxygen species levels may further compromise mitochondrial integrity and cause mitochondrial dysfunction. Reactive oxygen species serve as key signaling molecules in copper-induced neuroinflammation, with elevated levels activating several critical inflammatory pathways. Additionally, copper can bind aberrantly to several neuronal proteins, including alpha-synuclein, tau, superoxide dismutase 1, and huntingtin, thereby inducing neurotoxicity and ultimately cell death. This study focuses on the latest literature evaluating the role of copper in neurodegenerative diseases, with a particular focus on copper-containing metalloenzymes and copper-binding proteins in the regulation of copper homeostasis and their involvement in neurodegenerative disease pathogenesis. By synthesizing the current findings on the functions of copper in oxidative stress, neuroinflammation, mitochondrial dysfunction, and protein misfolding, we aim to elucidate the mechanisms by which copper contributes to a wide range of hereditary and neuronal disorders, such as Wilson's disease, Menkes' disease, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease, and multiple sclerosis. Potential clinically significant therapeutic targets, including superoxide dismutase 1, D-penicillamine, and 5,7-dichloro-2-[(dimethylamino)methyl]-8-hydroxyquinoline, along with their associated therapeutic agents, are further discussed. Ultimately, we collate evidence that copper homeostasis may function in the underlying etiology of several neurodegenerative diseases and offer novel insights into the potential prevention and treatment of these diseases based on copper homeostasis.}, } @article {pmid39587033, year = {2024}, author = {Green, AR and Chakrabarti, S and Shivakumar, S and Hughes, C and Banerjee, S and Kinyanjui, MW and Mbizah, MM and Ohrens, O and Thiemkey, AR}, title = {Creating constellations of coexistence through connections between people in human-wildlife conflict areas.}, journal = {Conservation biology : the journal of the Society for Conservation Biology}, volume = {38}, number = {6}, pages = {e14402}, pmid = {39587033}, issn = {1523-1739}, support = {//Macalester College Dewitt Wallace Library Open Access Fund/ ; }, mesh = {*Conservation of Natural Resources/methods ; Humans ; Animals ; Biodiversity ; Animals, Wild ; Human-Animal Interaction ; }, abstract = {Human-wildlife conflict (HWC) is a critical challenge to human development and well-being and threatens biodiversity conservation. Ideally, HWC mitigation should benefit both wildlife and communities and limit the costs associated with living alongside wildlife. However, place- and context-dependent realizations of conflict are often overlooked in HWC mitigation. Social and systemic dimensions of human-wildlife relationships often receive limited consideration in HWC as a concept and in mitigation strategies implemented globally. In recognizing our collective symmetries as a diverse group of researchers, we pose the idea of constellations of coexistence, based on Atallah et al.'s "constellation of co-resistance." Building on literature and our interdisciplinary and cross-sectoral experiences of working with diverse species inhabiting different sociocultural, sociopolitical, and socioeconomic landscapes, we considered evidence of cultural nuances (e.g., sociocultural dimensions of human-elephant and human-lion interactions in East Africa and India) in HWC mitigation and argue that failing to incorporate them in mainstream practices poses a myriad of ethical and practical consequences. Locally situated but globally relevant, participation of local and Indigenous communities in HWC mitigation activities produces better conservation outcomes. Centering communities in the ideation, implementation, and evaluation of HWC mitigation promotes more equitable and sustainable management strategies for long-term human-wildlife coexistence.}, } @article {pmid39565381, year = {2025}, author = {Miyazaki, K and Yamada, T and Kaida, H and Hanaoka, K and Ishii, K}, title = {The eagle-wing finding in FP-CIT SPECT, as a characteristic finding in patients with DESH- type iNPH.}, journal = {Neuroradiology}, volume = {67}, number = {1}, pages = {79-87}, pmid = {39565381}, issn = {1432-1920}, mesh = {Humans ; *Tomography, Emission-Computed, Single-Photon/methods ; Male ; Female ; *Tropanes ; Retrospective Studies ; Aged ; Radiopharmaceuticals ; *Hydrocephalus, Normal Pressure/diagnostic imaging ; Middle Aged ; Diagnosis, Differential ; Aged, 80 and over ; Dopamine Plasma Membrane Transport Proteins/metabolism ; }, abstract = {PURPOSE: Although dopamine transporter (DAT) imaging has been reported to be useful for differentiating idiopathic Normal Pressure Hydrocephalus (iNPH) from its mimics, the radiological findings of DAT imaging in iNPH have not been established. We investigated [[123]I] N-ω-fluoropropyl-2β-carboxymethoxy-3β-(4-iodophenyl) nortropane (FP-CIT) single photon emission computed tomography (SPECT) images from patients with disproportionately enlarged subarachnoid-space hydrocephalus (DESH)-type iNPH to understand the characteristics of DAT images of iNPH.

METHODS: We retrospectively collected 11 DESH-type iNPH patients without comorbidities who underwent FP-CIT SPECT imaging. The patients' FP-CIT SPECT were examined using both visual and quantitative evaluations. Visual assessment used Kahraman et al.'s five-step grading, and quantitative assessment used DaTView and MIM software to calculate specific binding ratios (SBRs) for four volumes of interest (VOIs): the entire striatum, caudate nucleus, anterior putamen, and posterior putamen. Intergroup comparisons were made between the DESH group and a normal control (NC) group adjusted for age and sex.

RESULTS: The visual assessment classified 91% of DESH patients as showing grade 4 'eagle-wing' on FP-CIT SPECT, with a Kappa coefficient of 0.601. The median SBR was lower in the DESH group than in the NC group for all four VOIs, and significantly lower in the anterior and posterior putamen (p < 0.05).

CONCLUSION: In DESH-type iNPH, FP-CIT SPECT imaging typically shows the 'eagle-wing' finding due to decreased DAT concentration in the putamen. Our results enhance the utility of FP-CIT SPECT in diagnosing iNPH and distinguishing it from mimics.}, } @article {pmid39561515, year = {2025}, author = {Fiveash, A and Bedoin, N and Tillmann, B}, title = {Examining methodological influences on the rhythmic priming effect: A commentary on Kim, McLaren, and Lee (2024).}, journal = {Journal of experimental child psychology}, volume = {250}, number = {}, pages = {106111}, doi = {10.1016/j.jecp.2024.106111}, pmid = {39561515}, issn = {1096-0457}, mesh = {Humans ; Child ; *Repetition Priming/physiology ; Language ; Female ; Male ; }, abstract = {The rhythmic priming effect (RPE) refers to improved language performance (typically grammaticality judgements) following regular rhythmic primes compared to various control conditions. This effect has been observed primarily in French, but also in English and Hungarian. However, a recent implementation by Kim, McLaren & Lee (2024), aiming to replicate the RPE in English (Chern, Tillmann, Vaughan & Gordon, 2018), was not successful, inviting a discussion about the conditions under which the RPE could be observed. We here discuss features of Kim et al.'s (2024) implementation that might have reduced the probability of observing the RPE. Compared to Chern et al. (2018), and numerous other studies reporting the RPE, additional delays after the primes and before each sentence were introduced by Kim et al. (2024). This change might have limited beneficial prime effects, which persist, but decay over time. Further, their instruction to "relax and have some rest" might have reduced attentive processing of the primes and related entrainment. Finally, their sample was small (n =16 per experiment) and with a large age range for investigating typically developing children (7-12y), potentially reducing experimental effects due to development-related individual variations. These methodological changes and sample characteristics are discussed in relation to previous research on the RPE, and entrainment in general. This discussion prompts the need for future research to investigate conditions leading to the RPE, with the aim to shed light on underlying mechanisms. Better understanding the RPE will be critical for the use of rhythmic priming within clinical and educational settings.}, } @article {pmid39560813, year = {2024}, author = {Ergen, Hİ and Yiğit, S and Maden, T and Keskinbıçkı, MV}, title = {The Turkish version of the brief Michigan hand outcomes questionnaire: cross-cultural adaptation, validity, and reliability testing.}, journal = {Acta orthopaedica et traumatologica turcica}, volume = {58}, number = {5}, pages = {286-289}, pmid = {39560813}, issn = {2589-1294}, mesh = {Humans ; Turkey ; Reproducibility of Results ; Female ; Male ; Surveys and Questionnaires ; *Disability Evaluation ; Adult ; Middle Aged ; *Cross-Cultural Comparison ; Pain Measurement/methods ; Translations ; Hand/physiopathology ; Hand Injuries ; Psychometrics/methods ; }, abstract = {OBJECTIVE: This study aimed to develop the Turkish version of the Brief Michigan Hand Outcomes Questionnaire (B-MHQ) and to demonstrate its reliability and validity for evaluating hand function in the Turkish population with hand/wrist disorders.

METHODS: This study was conducted in accordance with Beaton et al.'s Guidelines for the Process of Cross-Cultural Adaptation of SelfReport Measures. A total of 54 patients with various hand and wrist problems were included in the study. The B-MHQ and Quick Disabilities of the Arm, Shoulder, and Hand (Q-DASH) were used to evaluate hand function, and the visual analog scale (VAS) was used for the assessment of pain, which were completed by the subjects at baseline and 7 days later.

RESULTS: The Turkish version of the B-MHQ showed good internal consistency, as evidenced by Cronbach alpha coefficients ranging from 0.895 to 0.876, and excellent test-retest reliability with an intraclass correlation coefficient of 0.968. In addition, B-MHQ was strongly correlated with Q-DASH (r=-0.878) and moderately correlated with VAS (r=-0.445).

CONCLUSION: The Turkish version of the B-MHQ seems to be a reliable and valid tool for assessing hand function in Turkish-speaking patients with hand disorders.

LEVEL OF EVIDENCE: Level III, Diagnostic Study.}, } @article {pmid39557995, year = {2024}, author = {Enichen, EJ and Heydari, K and Wang, S and Nickel, GC and Kvedar, JC}, title = {The utility of personal wearable data in long COVID and personalized patient care.}, journal = {NPJ digital medicine}, volume = {7}, number = {1}, pages = {326}, pmid = {39557995}, issn = {2398-6352}, abstract = {Radin et al.’s recent study on patients with long COVID demonstrates that personal wearable data can provide critical insight into complex conditions. This editorial argues that research insights gained through personal wearables support the integration of personal wearables into healthcare. Challenges in incorporating wearable data in the clinic point towards AI data sorting, data sharing, device interoperability, FDA oversight, and expanded insurance coverage as first steps towards addressing these challenges.}, } @article {pmid39557175, year = {2025}, author = {Liu, Y and Zhang, B and Ye, J and Zhang, Z and Liu, R and Li, M and Chen, X and Yu, T and Liang, B and Wang, X and Li, R and Yuan, C and Guo, H}, title = {The effects of reference selection methods on PROPELLER MRI.}, journal = {Magnetic resonance imaging}, volume = {116}, number = {}, pages = {110275}, doi = {10.1016/j.mri.2024.110275}, pmid = {39557175}, issn = {1873-5894}, mesh = {Humans ; *Magnetic Resonance Imaging/methods ; *Algorithms ; *Image Processing, Computer-Assisted/methods ; Motion ; Brain/diagnostic imaging ; Artifacts ; Computer Simulation ; Reproducibility of Results ; Adult ; Male ; Female ; }, abstract = {PROPELLER MRI has been shown effective for rigid motion compensation, while the performance of existing PROPELLER reconstruction methods critically depend on selecting a proper reference blade. In this work, we proposed a robust implementation for PROPELLER reconstruction, which was incorporated with different reference selection methods, including single blade reference (SBR), combined blades reference (CBR), grouped blades reference (GBR) and Pipe et al.'s revised method, which requires no blade reference (NBR). Both simulation and in vivo studies were performed to evaluate the precision and robustness of motion estimation for reference selection methods. In vivo data sets from 10 volunteers with instructed motion and 11 patients with random motion were collected and images were scored independently and blindly by two experienced radiologists. Both simulation and in vivo studies demonstrate that the four reference selection methods have similar performances according to visual inspection. In our tests, one iteration for the motion estimation can be sufficient for SBR, CBR, or GBR, and comparable to NBR in terms of image quality for clinical diagnosis. With two iterations, SBR, CBR, and GBR are comparable to NBR in terms of motion estimation precision. With our proposed PROPELLER reconstruction, reference selection is not critical for robust motion correction. NBR with no iterations and SBR, CBR, and GBR with two iterations are recommended for accurate motion correction.}, } @article {pmid39551194, year = {2024}, author = {Chu, KH and Bollinger, JC}, title = {A critique of Rajendran et al.'s "A critical and recent developments on adsorption technique for removal of heavy metals from wastewater - A review".}, journal = {Chemosphere}, volume = {368}, number = {}, pages = {143761}, doi = {10.1016/j.chemosphere.2024.143761}, pmid = {39551194}, issn = {1879-1298}, mesh = {Adsorption ; *Metals, Heavy/chemistry/analysis ; Waste Disposal, Fluid/methods ; *Wastewater/chemistry ; *Water Pollutants, Chemical/analysis/chemistry ; Water Purification/methods ; }, abstract = {This critique examines a review article in this journal on adsorption techniques for removing metal ions from wastewater. The article is marred by several flaws, including tortured phrases, miscitations, incoherent statements, and factual inaccuracies. These problems weaken the article's clarity and reliability, raising doubts about the authors' understanding of the subject. As a result, the review's credibility is compromised, limiting its value as a reliable resource for researchers. This critique highlights these issues, stressing the importance of accuracy and rigor in scientific writing.}, } @article {pmid39548440, year = {2024}, author = {Finderup, J and Bekker, HL and Albèr, NT and Boel, S and Buur, LE and von Essen, HS and Kristensen, AW and Lyng, KD and Vedelø, TW and Rasmussen, GS and Skovlund, PC and Søndergaard, SR and Giguère, A}, title = {Measuring healthcare professionals' perceptions of their ability to adopt shared decision making: Translation and psychometric evaluation of the Danish version of the IcanSDM questionnaire.}, journal = {BMC medical informatics and decision making}, volume = {24}, number = {1}, pages = {340}, pmid = {39548440}, issn = {1472-6947}, mesh = {Humans ; *Psychometrics/standards ; *Decision Making, Shared ; Denmark ; Adult ; Male ; Female ; *Health Personnel ; Surveys and Questionnaires/standards ; Translations ; Middle Aged ; Attitude of Health Personnel ; Translating ; Reproducibility of Results ; }, abstract = {BACKGROUND: Shared decision making in healthcare is a fundamental right for patients. Healthcare professionals' perception of their own abilities to enable shared decision making is crucial for implementing shared decision making within service. IcanSDM (I can shared decision making) is a brief measure to investigate healthcare professionals' perception of shared decision making approaches to their practices. It was developed in Canada with French and English versions, and recently translated into German. This study aims to adapt the IcanSDM measure for Danish-speaking healthcare professionals, and evaluate its psychometric properties.

METHODS: Cultural adaptation and translation based on Beaton et al.'s approach was applied. A forward translation by ten people and a backward translation by two people were performed. To assess comprehensibility, cognitive interviews were conducted with 24 healthcare professionals. Eighty healthcare professionals who were trained in shared decision making for either one hour (n = 65) or one day (n = 15) participated in the psychometric evaluation. The evaluation concerned acceptance, item characteristics, skewness, item difficulties, corrected item-total correlations, inter-item correlations, factorial structure, internal consistency, and responsiveness.

RESULTS: The forward and backward translation revealed few discrepancies, and participants understood the items well. The psychometric evaluation showed a high completion rate and acceptable item difficulties and discrimination values. Both the factor analysis and the internal consistency showed a 2-factor structure: 1) healthcare professionals' capacity to implement shared decision making; and 2) healthcare professionals' capacity to practise shared decision making. The IcanSDM_Danish obtained a Cronbach's alpha coefficient of 0.74. The evaluation of responsiveness showed improvement, but was not statistically significant.

CONCLUSION: The IcanSDM_Danish has good cross-cultural validity and internal consistency, and a 2-factor structure. The IcanSDM_Danish is capable of providing reliable and valid measurement when evaluating constructed knowledge about shared decision making, and may be able to support the implementation of shared decision making training and evaluation of its impact.}, } @article {pmid39545947, year = {2025}, author = {Kingsland, SE and Taiz, L}, title = {Reply to Calvo, Raja, and Segundo-Ortin, "Don't jump the gun quite yet: aiming for the true target in plant neurobiology research".}, journal = {Protoplasma}, volume = {262}, number = {2}, pages = {277-278}, pmid = {39545947}, issn = {1615-6102}, mesh = {*Neurobiology ; *Plants ; }, abstract = {We reply to the response by P Calvo, V Raja, and M Segundo-Ortin to our article titled "Plant 'intelligence' and the misuse of historical sources as evidence." Their response draws on the authority of psychologist Edward C. Tolman in support of their suggestion that the study of plant intelligence requires an interdisciplinary approach, including cognitive science and other disciplines. We argue that there is no justification for using Tolman as an authority in support of the study of plant intelligence. For Tolman, psychology was confined to the study of organisms with brains, and therefore his comment, when taken in context, has no bearing on the subject of plant intelligence. Calvo et al.'s use of this quotation is a further example of the misuse of a historical authority to support their claim that disciplines such as cognitive science can be applied to the study of those plant behaviors that they consider to be "intelligent."}, } @article {pmid39540802, year = {2025}, author = {Shang, B and Hu, Z and Xie, R and Wu, J and Qu, W and Zhang, W and Zhou, A and Feng, L and Bi, X and Shou, J}, title = {Predictive Value of Neutrophil Extracellular Traps in Neoadjuvant Chemotherapy for Muscle-Invasive Bladder Cancer.}, journal = {Molecular carcinogenesis}, volume = {64}, number = {2}, pages = {305-316}, doi = {10.1002/mc.23844}, pmid = {39540802}, issn = {1098-2744}, support = {//This work was supported by The National Natural Science Foundation of China (ID Number: 82072837). This study was also funded by the Clinical and Translational Medicine Research Project of Chinese Academy of Medical Sciences (2022-I2M-C&T-B-056), Beijing Municipal Natural Science Foundation (ID Number: 7212083), and CAMS Initiative for Innovative Medicine (CAMS-I2M) [2021-I2M-C&T-B-052]./ ; }, mesh = {Humans ; *Urinary Bladder Neoplasms/drug therapy/pathology/metabolism ; *Extracellular Traps/metabolism ; Female ; Male ; Neoadjuvant Therapy/methods ; *Neutrophils/metabolism/pathology ; Middle Aged ; Prognosis ; Aged ; *Biomarkers, Tumor/metabolism ; Neoplasm Invasiveness ; Cisplatin/therapeutic use ; }, abstract = {Cisplatin-based chemotherapy is the recommended therapy for muscle-invasive bladder cancer (MIBC). However, the efficacy of MIBC for chemotherapy is only about 40%. Therefore, predictors of therapy response are urgently needed. Neutrophils form neutrophil extracellular traps (NETs), a network structure, and growing evidence indicated that it could be a prognostic and predictive marker in cancer. In MIBC, the predictive role of NETs in chemotherapy resistance is unclear. We used the Least Absolute Shrinkage and Selection Operator (LASSO) logistic regression analyses to develop a NETs-associated signature score (NETs-score) for therapeutic response prediction in the discovery cohort (GSE169455). Then the NETs score-based risk stratification was verified in two validation cohorts (Taber et al.'s cohort, our institutional cohort). In the training cohort, high NETs-score was associated with poor chemotherapy response (AUC = 0.781) and reduced recurrence-free survival (RFS) (hazard ratio [HR] = 2.07, 95% confidence interval [CI]: [1.26-3.40], p = 0.003) in MIBC patients. The NETs-score was also demonstrated to be a predictive factor for the efficacy of neoadjuvant chemotherapy in the validation cohort (AUC = 0.731). The accuracy of the NETs-score was superior to other chemotherapy response predictors such as Ba/Sq expression subtype (AUC = 0.711), BRCA2 mutation (AUC = 0.692) and ERCC2 mutation (AUC = 0.548). Furthermore, in our center cohort, the expression level of H3Cit showed a significant difference between the response and no-response group (p = 0.01). Through immunohistochemical validation, NETs was an independent predictor of MIBC neoadjuvant chemotherapy efficacy as determined by the multivariate logistic regression analysis (OR = 5.94, 95% CI: 1.20-45.50, p = 0.045). Patients with high levels of NETs predicted poor response to neoadjuvant chemotherapy. This study was the first to reveal the correlation between the level of NETs in MIBC and the efficacy of chemotherapy, which may provide a theoretical basis regarding NETs inhibitors.}, } @article {pmid39540594, year = {2024}, author = {Rogoff, B and Aceves-Azuara, I}, title = {Mother-child collaboration in an Indigenous community: Changing and enduring across generations.}, journal = {Child development}, volume = {95}, number = {6}, pages = {1858-1878}, pmid = {39540594}, issn = {1467-8624}, support = {//Spencer Foundation/ ; //Consejo Nacional de Humanidades, Ciencias y Tecnologías/ ; //SEP/ ; }, mesh = {Humans ; *Mother-Child Relations/ethnology ; Female ; Guatemala/ethnology ; Child ; Adult ; Child, Preschool ; Longitudinal Studies ; Male ; Infant ; Cooperative Behavior ; Indigenous Peoples ; }, abstract = {Changes in family life related to globalization may include reduction in the collaborativeness observed in many Indigenous American communities. The present study examined longitudinal changes and continuities in collaboration in a Guatemalan Maya community experiencing rapid globalization. Fluid collaboration was widespread 3 decades ago among triads of mothers and 1- to 6-year-olds in 24 Mayan families exploring novel objects during home visits (Dayton et al., 2022). However, in the "same" situation 30 years later, 22 mother-child triads of their relatives spent half as much time in collaboration among all three people. This aligns with globalizing changes and with the pattern of Dayton et al.'s middle-class European American families. Nonetheless, the Mayan families maintained harmonious interactions, in line with preserving important cultural values.}, } @article {pmid39538080, year = {2024}, author = {Liang, I and Tay, DL and Kirchhoff, AC and Schwanke, G and Ellington, L and Pisu, M and Mooney, K}, title = {Financial toxicity of total cancer care immunotherapy patients and caregivers: impacts of COVID-19 pandemic and inflation.}, journal = {Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer}, volume = {32}, number = {12}, pages = {790}, pmid = {39538080}, issn = {1433-7339}, support = {K07AG068185//National Institute of Aging/ ; }, mesh = {Humans ; *COVID-19/economics ; Middle Aged ; *Neoplasms/therapy/economics ; Male ; Female ; *Caregivers/psychology/economics ; *Immunotherapy/methods/economics/adverse effects ; Aged ; Cost of Illness ; Adult ; }, abstract = {PURPOSE: Financial toxicity, cancer-treatment-related financial harm, is associated with expensive treatments like immunotherapy. The purpose of this study was to explore financial toxicity among advanced cancer patients receiving immunotherapies and their caregivers and, secondarily, to study how recent inflation and the COVID-19 pandemic impacted these experiences.

METHODS: Advanced cancer patients receiving immunotherapies and their caregivers were recruited to participate in semi-structured interviews about supportive care needs from 2022 to 2023. The Comprehensive Score for Financial Toxicity was collected. Guided by Jones et al.'s cancer financial toxicity model, the content analysis was conducted by two trained coders using NVIVO R1.

RESULTS: Sixteen patients and 10 caregivers (including 7 dyads) across 5 states participated in interviews in 2022-2023. Participants averaged 63.43 years (SD = 12.75), and patients received an average of 14.6 months of immunotherapy (SD = 9.415). The majority lived in non-metropolitan areas (67%) and were white (95%). Three theory-driven themes were developed: (1) Sources of Financial Toxicity, (2) Buffers of Financial Toxicity, and (3) Consequences of Financial Toxicity. Inflation was added to financial toxicity for non-metropolitan dwelling participants due to increased prices of gas and accommodation. Social support systems buffered the impact of financial toxicity. Material and psychological impacts of financial toxicity disproportionately affected younger and privately insured participants.

CONCLUSION: While immunotherapy patients face high medical costs of treatment, the burdens of accessing treatment for people living at a distance from the cancer center can exacerbate financial toxicity. Clinicians and researchers should also consider external financial pressures such as national economic impacts that compound the financial toxicity of treatment.}, } @article {pmid39526636, year = {2024}, author = {Tsai, YY and Wei, LC}, title = {Enhancing Perinatal Cannabis Use Counseling: Insights From Taiwan's Addiction Treatment Practice.}, journal = {Birth (Berkeley, Calif.)}, volume = {51}, number = {4}, pages = {878-879}, doi = {10.1111/birt.12898}, pmid = {39526636}, issn = {1523-536X}, mesh = {Humans ; Female ; Taiwan ; Pregnancy ; *Counseling/methods ; Pregnancy Complications/therapy/psychology ; Marijuana Abuse/therapy/psychology ; Adult ; Perinatal Care/methods ; }, abstract = {This letter responds to Cernat et al.'s study on counseling about cannabis use during pregnancy and lactation, drawing parallels with addiction treatment practices in Taiwan. We highlight the importance of open, non-judgmental approaches and harm reduction strategies in counseling pregnant women with substance use disorders. Our experience at a psychiatric center in Taiwan emphasizes the need for continuous counseling throughout pregnancy and postpartum, particularly given the observed increase in cannabis use among new mothers. We support the study's emphasis on exploring patients' perceived benefits from cannabis use and addressing underlying reasons for use. By integrating insights from qualitative studies on patient perspectives, we have improved patient engagement and outcomes in our practice. This commentary underscores the global relevance of the study's findings and calls for continued research to bridge the gap between clinician and patient experiences in perinatal cannabis use counseling.}, } @article {pmid39520258, year = {2025}, author = {Cianciolo, AT and Konopasky, A and Jain, NR and Wyatt, TR and Ibrahim, H and Chow, CJ and Andon, A and Torre, D and Naidu, T}, title = {What can a journal editorial team do to strive for equity in health professions education publishing? Leading by example.}, journal = {Medical teacher}, volume = {47}, number = {6}, pages = {946-948}, doi = {10.1080/0142159X.2024.2425026}, pmid = {39520258}, issn = {1466-187X}, mesh = {Humans ; *Health Occupations/education ; *Periodicals as Topic/standards ; *Publishing/standards ; *Education, Medical ; Peer Review ; Peer Review, Research ; }, abstract = {Representation gaps in medical education publishing are widely recognized and may be attributed to epistemic injustice, defined as 'wrong done to someone in their capacity as a knower.' Although peer review is meant to ensure 'rigor,' some quality assurance practices can inadvertently silence entire populations and impede understanding of a field's foundational concepts.

To honor our journal's commitment to equitable knowledge production, a diversity, equity, and inclusion working group at Teaching and Learning in Medicine (TLM) reimagined rigor to include striving for a 'more equitable, diverse, and inclusive research system.'

We implemented structural peer review reform at TLM by adapting Hogan et al.'s Dimensionality and R4P framework for health equity, prioritizing change in our communication with contributors.

Since implementation, our journal has received feedback expressing appreciation for humanity and personal connection in our peer review, and we have observed increased publications from geographically marginalized authors. We believe our outcomes result from respecting marginalized authors' authority to pursue their own interests, concerns, and successes with respect to knowledge production.

WHAT ARE THE NEXT STEPS?: We believe our approach can be adopted by other peer-reviewed journals. We invite application and critique of our framework to advance community development in creating relevant, accessible, and equitable knowledge production for all people.}, } @article {pmid39520248, year = {2025}, author = {Ji, C and Garcia, J and Sabuga, AJ and Ricard, M and Dion, F and Rosu, VA and Legris, MÈ and Marsot, A and Nguyen, VD}, title = {External evaluation of intravenous vancomycin population pharmacokinetic models in adults receiving high-flux intermittent haemodialysis.}, journal = {British journal of clinical pharmacology}, volume = {91}, number = {3}, pages = {856-865}, pmid = {39520248}, issn = {1365-2125}, support = {//Amélie Marsot acknowledges support from the Fonds de Recherche du Québec-Santé (FRQS) Research Scholars-Junior 1 (Young Researcher Establishment) Career/ ; //Faculty of Pharmacy of the University of Montreal/ ; }, mesh = {Humans ; *Vancomycin/pharmacokinetics/administration & dosage ; *Anti-Bacterial Agents/pharmacokinetics/administration & dosage ; *Renal Dialysis/methods/adverse effects ; Retrospective Studies ; *Models, Biological ; Drug Monitoring/methods ; Middle Aged ; Male ; Methicillin-Resistant Staphylococcus aureus/drug effects ; Female ; Aged ; Adult ; Staphylococcal Infections/prevention & control/drug therapy ; Nomograms ; Administration, Intravenous ; }, abstract = {AIMS: Patients undergoing haemodialysis (HD) are at greater risk of methicillin-resistant Staphylococcus aureus infections requiring intravenous vancomycin. Close vancomycin therapeutic drug monitoring is warranted in HD patients as renal clearance is the primary elimination pathway. Clinically, population pharmacokinetics (popPK) model-informed dosing is commonly used. This study aimed to perform an external evaluation of published vancomycin popPK models developed for adults undergoing high-flux intermittent HD, and to create a dosing nomogram derived from the model that performed best.

METHODS: A literature review was conducted through PubMed and EMBASE to identify relevant popPK models. an external dataset was collected retrospectively from patients of 2 healthcare centres in Quebec, Canada. Selected models were implemented in NONMEM (v7.5; ICON Development Solutions). Predictive performance was assessed through prediction and simulation-based diagnostics.

RESULTS: In total, 2386 vancomycin concentrations were collected from 274 patients and 476 antibiotic courses. Four vancomycin popPK models were selected for evaluation. None of the models demonstrated overall satisfactory or clinically acceptable predictive performance. Nonetheless, Bae et al.'s model performed best with a median prediction error of 16.25% and median absolute prediction error of 34.66%. Different predictive performance was also observed for vancomycin concentrations from samples collected during and between HD sessions.

CONCLUSION: All evaluated models presented poor overall predictive performance. Further studies are required, through existing popPK model parameter re-estimation or new model development, to adequately describe vancomycin pharmacokinetics for our high-flux intermittent HD patient cohort.}, } @article {pmid39514721, year = {2024}, author = {Kelty-Stephen, DG and Mangalam, M}, title = {Ball Don't Lie: Commentary on Chemero (2024) and Wallot et al. (2024).}, journal = {Topics in cognitive science}, volume = {}, number = {}, pages = {}, doi = {10.1111/tops.12764}, pmid = {39514721}, issn = {1756-8765}, abstract = {The interaction-dominant approach to perception and action, originally formulated in the mid-1990s, has matured and gained remarkable momentum as an entailment of the dynamical hypotheses proposed at that time. This framework seeks to explain the fluid and intricate interplay of causality spanning the entire organism by integrating high-dimensional details with low-dimensional constraints across various scales of behavior. Both Chemero (2024) and Wallot et al. (2024) have skillfully explored the theoretical implications and methodological challenges this perspective introduces. We echo Chemero's (2024) and Wallot et al.'s (2024) focus on multifractality, while also underscoring new efforts to model the synergetic relationships and cascading dynamics inherent in this interaction-dominant approach.}, } @article {pmid39513187, year = {2024}, author = {Bozonnat, A and Serret-Larmande, A and Beylot-Barry, M and Bagot, M and de Masson, A and , }, title = {Response to Campbell et al.'s comments on our study "Real-life efficacy of immunotherapy for Sézary syndrome: a multicenter observational cohort study".}, journal = {EClinicalMedicine}, volume = {77}, number = {}, pages = {102895}, pmid = {39513187}, issn = {2589-5370}, } @article {pmid39512096, year = {2024}, author = {Vranceanu, AM and Szapary, C}, title = {The partner paradox: How can we better understand shared cognitive decline in couples?.}, journal = {Journal of Alzheimer's disease : JAD}, volume = {102}, number = {2}, pages = {308-310}, doi = {10.1177/13872877241289056}, pmid = {39512096}, issn = {1875-8908}, mesh = {Humans ; *Cognitive Dysfunction/psychology ; *Spouses/psychology ; }, abstract = {Shared cognitive decline among spouses remains in the early stages of being understood. In this commentary, we discuss Meng et al.'s systematic review and meta-analysis, which synthesizes the evidence for concordance of cognitive decline in couples. The study's methodology is robust and brings to light the challenges that persist within this field of research, namely the lack of specificity and standardization across outcomes and long-term follow-up. Here, we also situate the findings within the broader context of the many social influences on health and underscore the importance of dyadic preventive strategies and future longitudinal and mechanistic research.}, } @article {pmid39507469, year = {2024}, author = {DeJohn, J and Ahluwalia, T and Madhok, M and Gidwani, S and Douglass, K and Owens, S}, title = {Bridging Hospital Resource Variability: Adapting the Escape Room to Integrate Procedure Teaching for Emergency Medicine Trainees in India.}, journal = {Journal of education & teaching in emergency medicine}, volume = {9}, number = {4}, pages = {S24-S48}, pmid = {39507469}, issn = {2474-1949}, abstract = {AUDIENCE: This is an in-person escape room and procedure simulation activity based on complications of human immunodeficiency virus (HIV) in India, which was created by using local HIV management guidelines. Emergency Medicine (EM) trainees of all post-graduate levels are the target audience. This may also be used by trainees in other specialties, such as infectious disease or internal medicine, who require an understanding of HIV and its complications. This escape room can be completed in teams of varying sizes and is designed to be adaptable to local resource availability.

BACKGROUND: Patients with HIV present to the Emergency Department (ED) for a variety of reasons such as initial viral syndrome, medication side effects, and opportunistic infections. While the widespread use of antiretroviral therapy (ART) has significantly increased the life expectancy of patients living with HIV and decreased the incidence of classical opportunistic infections, EM providers should still be vigilant and competent in diagnosing and managing these pathologies. This is particularly critical in India, where the prevalence of HIV was most recently estimated at 0.22% (2.2 million people older than 15 years) in 2020.1 This patient population, primarily infected through unprotected heterosexual contact, is at high risk for interruptions in ART and development of opportunistic infections for a variety of reasons including migration for work, low social status of women, and significant social stigma against HIV.2 Simulation is an educational opportunity to review these high-acuity low-occurrence presentations to prepare EM trainees for independent practice.

EDUCATIONAL OBJECTIVES: By the end of the escape room, learners should be able to: 1) describe the mechanism of action of antiretroviral therapies available in India, 2) prescribe initial antiretroviral therapy to a patient presenting to the emergency department with a new diagnosis of HIV, 3) develop a differential diagnosis for a patient with HIV presenting to the ED with chest pain, 4) identify common dermatologic manifestations of opportunistic infections in patients with HIV, 5) identify computerized tomography scan and lumbar puncture features for central nervous system infections seen in patients with Acquired Immunodeficiency Syndrome (AIDS), 6) identify red flag features and appropriate workup for a patient with HIV presenting with a headache to the ED, 7) interpret images obtained during a Rapid Ultrasound for Shock and Hemorrhage (RUSH) exam, 8) identify cardiac tamponade and perform a pericardiocentesis, and 9) communicate and collaborate as a team to manage a complex, unstable patient with HIV in the ED.

EDUCATIONAL METHODS: We sought to create and implement an educational tool that could meet the complex education needs of EM trainees while being low cost, easily adapted to local resources, and engaging for trainees. Hospitals participating in the Masters in Emergency Medicine (MEM) program, a global partnership between the Ronald Reagan Institute for Emergency Medicine at the George Washington University and 18 hospitals in India, have resource variability for traditional simulation. The escape room created combines simulation, content review specific to the contextual practice of EM in India focused on HIV and its complications, and critical procedure teaching on pericardiocentesis. This innovation framework is based on Kolb's experiential learning cycle and incorporates the gamification principles of a sense of autonomy, perception of competitiveness, and learner-relatedness.3-4 Escape rooms have been shown to engage learners, and low-fidelity procedure models could further maximize the experience for learners in resource variable settings.5 A pericardiocentesis model was adapted from Lord et al.'s low-fidelity model, ensuring it could be assembled with materials readily available in-country.6.

RESEARCH METHODS: We adapted the escape room format to combine simulation, content review, and procedural training in a cost-effective, contextually relevant, and scalable way. The escape room was trialed using a case of chest pain and altered mental status caused by a pericardial effusion due to tuberculosis in a patient with HIV. Local practice patterns and guidelines were used to develop puzzles and clinical clues. A pericardiocentesis model was constructed using materials readily available in India. Pre- and post-surveys were developed to assess baseline trainee experience with escape rooms, self-reported knowledge of the differential diagnosis and management for altered mental status, and ways to incorporate escape room content into daily practice.

RESULTS: A total of 47 trainees participated; 41 of 47 participants completed both pre- and post-surveys (87% response rate). Participants represented all program trainee levels: 49% (n = 20) PGY-1, 27% (n = 11) PGY-2, and 24% (n = 10) PGY-3. Based on a score greater than seven on a 1-10 Likert scale, the escape room was rated as "highly effective" by 93.5% of respondents in reviewing medical knowledge. The trainees were allotted 60 minutes to escape the room; the median time for escape room completion was 57 minutes. The escape room and pericardiocentesis model cost under $100 USD, were repeated up to six times in one day, and could be recycled for future use.

DISCUSSION: Utilizing simulation in the escape room format that can be adaptable to variable resource settings is a valuable educational tool. The integrated escape room and procedure training proved to be an effective educational tool that was scalable and maintained efficacy across variable hospital resource levels. The next step includes adapting this format for other disease pathologies. This is a useful way to meet the education needs of MEM program trainees, regardless of hospital resource availability, that could be replicable in other EM training programs.

TOPICS: HIV, AIDS, dermatologic manifestations of HIV, HIV medications, CNS complications of HIV, chest pain, headache, tuberculosis, RUSH exam, pericardiocentesis, escape room, simulation.}, } @article {pmid39501147, year = {2024}, author = {Perron, ME and Hudon, C and Roux-Levy, PH and Poitras, ME}, title = {Shared decision-making with patients with complex care needs: a scoping review.}, journal = {BMC primary care}, volume = {25}, number = {1}, pages = {390}, pmid = {39501147}, issn = {2731-4553}, mesh = {Humans ; *Decision Making, Shared ; *Patient Participation/methods/psychology ; Multimorbidity ; }, abstract = {BACKGROUND: A number of patients have complex care needs that arise from interactions among multiple factors, such as multimorbidity, mental health issues, and social vulnerability. These factors influence decisions about healthcare and health services. Shared decision-making (SDM), a collaborative process between patients and professionals, is known to improve the quality of the decision-making process. However, follow-up challenges of patients with complex care needs (PCCNs) can lead to SDM specificities.

OBJECTIVE: To identify specificities of SDM with PCCNs.

METHODS: We conducted a scoping review using the Joanna Briggs Institute (JBI) methodology. We conducted a systematic search across MEDLINE, CINAHL, PsycINFO, and Academic Search Complete databases. Empirical studies about SDM with PCCNs published between 1997 and 2023 were eligible for inclusion. We conducted a mixed thematic analysis using deductive (Ottawa Decision Support Framework and Interprofessional Shared Decision-Making Model) and inductive approaches. Following Arksey & O'Malley's and Levac et al.'s methodological recommendations, we consulted experts (researchers, healthcare professionals, and patient partners) to enhance the findings.

RESULTS: Twelve studies were included in the review. Overall, our results demonstrated the importance of recognizing some specificities of SDM with PCCNs, such as the simultaneous presence of multiple decisions and the multidisciplinary and intersectoral nature of the healthcare and health services they receive.

CONCLUSION: This scoping review highlights some specificities that must be considered in SDM with PCCNs to maintain its already-known benefits and ensure positive health and decision-making outcomes.}, } @article {pmid39498497, year = {2024}, author = {Bakaa, L and Al-Mosawi, F and Bakaa, N and de Oliveira, LA and Laberge, M and Macedo, LG}, title = {Content validation of the COST for patient questionnaire (COPAQ) for patients with low back pain: a qualitative study.}, journal = {International journal of technology assessment in health care}, volume = {40}, number = {1}, pages = {e46}, pmid = {39498497}, issn = {1471-6348}, mesh = {Humans ; *Low Back Pain/therapy/economics ; Middle Aged ; Adult ; Cross-Sectional Studies ; Male ; Female ; Aged ; Surveys and Questionnaires/standards ; *Qualitative Research ; Reproducibility of Results ; Interviews as Topic ; }, abstract = {INTRODUCTION: The costs of low back pain (LBP) are complex and difficult to estimate. This study aims to adapt the Cost for Patients Questionnaire (CoPaQ) for use in LBP populations.

MATERIALS AND METHODS: In a cross-sectional qualitative study, we conducted cognitive interviews to assess the CoPaQ's suitability for addressing costs related to LBP. Three groups of participants were included (n = 5 each): (i) persons with a history of LBP or primary caregiver, (ii) researchers with expertise in LBP, and (iii) primary care providers specialized in treating LBP. The interpretation, analysis, and summary of results used Knafl et al.'s qualitative content analysis method.

RESULTS: Persons with a history of LBP (n = 5), had a median age of 60 years (Interquartile Range (IQR): 26-71.5), and varying durations of LBP, the median duration of LBP 7 years (IQR: 4-32.5). Researchers (n = 5) had a median age of 33 years (IQR: 29-45). Primary care providers (n = 5) had a median age of 40 years (IQR: 37.5-65), and a background in chiropractic care (n = 3) and physiotherapy (n = 2). Content analysis of the interviews revealed sources of error with five pre-determined themes (clarity/comprehension, relevance, inadequate response definition, reference point, perspective modifiers) and one developed theme (organization). We modified the questionnaire for LBP populations based on the feedback.

CONCLUSION: Our study evaluated the content validity of a questionnaire that assesses the direct and indirect costs associated with LBP. Future studies should pilot this questionnaire with persons of varying LBP severity and compare it with cost diaries.}, } @article {pmid39497334, year = {2024}, author = {Adam-Troian, J and Bélanger, J}, title = {Beyond Eyeball Tests: A Methodical Rebuttal to Fillon et al.'s Commentary.}, journal = {Aggressive behavior}, volume = {50}, number = {6}, pages = {e70005}, doi = {10.1002/ab.70005}, pmid = {39497334}, issn = {1098-2337}, support = {//The authors received no specific funding for this work./ ; }, mesh = {Humans ; *Obsessive-Compulsive Disorder/psychology/diagnosis ; }, abstract = {In our original study, "Consumed by Creed" (Adam-Troian & Bélanger, 2024), we established significant and consistent associations between obsessive-compulsive disorder symptom severity and radical intentions across four distinct U.S. population samples-Environmentalists, Republicans, Democrats, and Muslims-partially or fully mediated by obsessive passion. Fillon et al. (2024) challenged our findings, alleging methodological errors and an excessive degree of researcher flexibility, which they claim could lead to false-positive results. In this response, we critically examine Fillon et al.'s commentary, arguing that it exemplifies flawed meta-scientific critique. We demonstrate that their approach relies on a series of unsupported and misleading claims, including a misinterpretation of the literature, unjustified reliance on visual data inspection, speculative assumptions about religious influences on our findings, and a shifting of the burden of proof. Through rigorous re-analyses, we reaffirm the robustness of our original results and address the unfounded allegations regarding our methodological practices. We also critique Fillon et al.'s approach, highlighting the necessity of domain-specific expertize in meta-scientific evaluations and cautioning against the risks of speculative and defamatory criticism in academic discourse. This exchange underscores the importance of maintaining rigorous standards in both original research and its critique, ensuring that scientific debate remains grounded in evidence rather than conjecture.}, } @article {pmid39495231, year = {2024}, author = {Xiao, LY}, title = {Mainland China's 2021 restrictions on under-18s' video game time were imposed when older 2019 restrictions already applied: Omitting the historical regulatory context is misleading.}, journal = {Journal of behavioral addictions}, volume = {}, number = {}, pages = {}, doi = {10.1556/2006.2024.00061}, pmid = {39495231}, issn = {2063-5303}, abstract = {Investigating the impacts of addiction policymaking following implementation is important. Effective policies should be considered for emulation elsewhere, whilst ineffective policies should be repealed. Zhou et al. (2024) reported how Mainland Chinese under-18s responded to the 2021 restrictions on their online videogame playtime, which were intended to curb online gaming addiction. However, Zhou et al. failed to mention that Mainland China had previously tried to achieve the same regulatory aim by imposing rules in 2019 that were more lenient than the 2021 rules but nonetheless restricted under-18s' gameplay time. These 2019 restrictions were neither acknowledged as crucial background in the introduction section nor accounted for by Zhou et al. when interpreting their results, thus giving readers the incorrect impression that the 2021 rules were the first ones introduced and that under-18s' gameplay time was not restricted at all prior to 2021. Importantly, Zhou et al.'s entire sample of young people therefore consisted not merely of 'heavy gamers' as they euphemistically described them as, but 'counterplayers' who actively contravened the 2019 rules. The misleading omission of this context is a major limitation and misrepresentation. The results should be interpreted accordingly and not overgeneralised.}, } @article {pmid39491625, year = {2025}, author = {Vrijsen, E and Van Bauwel, S and Dhoest, A and De Backer, C}, title = {Sizzling steaks and manly molds: Exploring the meanings of meat and masculinities in young men's lives.}, journal = {Appetite}, volume = {204}, number = {}, pages = {107754}, doi = {10.1016/j.appet.2024.107754}, pmid = {39491625}, issn = {1095-8304}, mesh = {Humans ; Male ; *Masculinity ; Adult ; Young Adult ; Adolescent ; Belgium ; Meat ; Feeding Behavior/psychology ; Diet/psychology ; Red Meat ; Food Preferences/psychology ; }, abstract = {Eating (red) meat and masculinity are historically and culturally associated, leading to the stereotype "real men eat meat" in western societies. Existing literature primarily examines men's motivations, justifications, and attitudes toward meat consumption; however, there is limited understanding of the themes that emerging adult men associate with their meat consumption and how these themes relate to their masculine identity. This study employed semi-structured interviews with thirty men aged 18 to 29, living in Flanders, Belgium. Through inductive analysis, we identified five meat themes (i.e. the topics men talk about when discussing their meat-eating behavior): "traditional cuisine", "doing meat", "fitness", "taste", and "meat ethics". Subsequently, these themes were deductively connected to the frameworks of Wong and Wang's (2022) model of masculinities and Piazza et al.'s (2015) 4N scale of meat justification to gain insight into the link between masculine identities and meat consumption. Finally, we formulated five "masculine meat identities": "normative", "performative", "embodied", "hedonistic" and "ethical" meat masculinities. Each identity reflects how men utilize meat, particularly red meat, for communicating and reinforcing their masculine identity, while also serving as a medium for expressing personal and social identities. This research contributes to a deeper understanding of how food, especially meat, operates as a means of communicating gender, bridging the disciplines of food and masculinities studies. Moreover, insights obtained from these masculine meat identities provide implications for public health, marketing, and policy. By tailoring strategies that resonate with diverse masculine identities, stakeholders can better align their initiatives with global health and sustainable objectives.}, } @article {pmid39488108, year = {2025}, author = {Xu, K and Wang, M and Zou, X and Liu, J and Wei, A and Chen, J and Tang, C}, title = {HSTrans: Homogeneous substructures transformer for predicting frequencies of drug-side effects.}, journal = {Neural networks : the official journal of the International Neural Network Society}, volume = {181}, number = {}, pages = {106779}, doi = {10.1016/j.neunet.2024.106779}, pmid = {39488108}, issn = {1879-2782}, mesh = {*Neural Networks, Computer ; *Algorithms ; Humans ; *Drug-Related Side Effects and Adverse Reactions ; }, abstract = {Identifying the frequencies of drug-side effects is crucial for assessing drug risk-benefit. However, accurately determining these frequencies remains challenging due to the limitations of time and scale in clinical randomized controlled trials. As a result, several computational methods have been proposed to address these issues. Nonetheless, two primary problems still persist. Firstly, most of these methods face challenges in generating accurate predictions for novel drugs, as they heavily depend on the interaction graph between drugs and side effects (SEs) within their modeling framework. Secondly, some previous methods often simply concatenate the features of drugs and SEs, which fails to effectively capture their underlying association. In this work, we present HSTrans, a novel approach that treats drugs and SEs as sets of substructures, leveraging a transformer encoder for unified substructure embedding and incorporating an interaction module for association capture. Specifically, HSTrans extracts drug substructures through a specialized algorithm and identifies effective substructures for each SE by employing an indicator that measures the importance of each substructure and SE. Additionally, HSTrans applies convolutional neural network (CNN) in the interaction module to capture complex relationships between drugs and SEs. Experimental results on datasets from Galeano et al.'s study demonstrate that the proposed method outperforms other state-of-the-art approaches. The demo codes for HSTrans are available at https://github.com/Dtdtxuky/HSTrans/tree/master.}, } @article {pmid39468524, year = {2024}, author = {Abdi, K and Najafi, Z and Foroughi, Z and Afshari, M}, title = {Health policy analysis for stewardship of rehabilitation services.}, journal = {BMC health services research}, volume = {24}, number = {1}, pages = {1301}, pmid = {39468524}, issn = {1472-6963}, mesh = {Humans ; *Health Policy ; Iran ; *Rehabilitation/standards ; Policy Making ; Qualitative Research ; }, abstract = {BACKGROUND AND AIM: There have been a growing interest in investigating the effect of stewardship on other functions of rehabilitation service delivery. Effective stewardship of rehabilitation services can ensure that these services are of high quality, accessible, affordable, and sustainable, and can help achieve the goals of universal health coverage. The purpose of this study was to identify and analyze the policies adopted in the field of rehabilitation services in Iran and in the international arena, and finally to identify policy gaps, areas for improvement, and areas that have been overlooked.

METHOD: This research is a policy analysis, carried out through document analysis and Dalglish et al.'s READ approach. Data were analyzed and interpreted using qualitative methodology and directed content analysis. For this purpose, Veillard et al.'s health system stewardship framework was used to analyze the stewardship of rehabilitation services. The dimensions of the stewardship framework, were: Defining the vision for health and strategies and policies to achieve better health; influencing all sectors and advocating for better health; ensuring good governance in line with prevailing values; ensuring the alignment of system design with health system goals; improving existing legal and regulatory instruments; and compiling, disseminating, and applying information. Scott's four criteria were used to assess the authenticity, credibility, representativeness, and meaning of the documents. Those that did not meet even one of the Scott's criteria were excluded from content analysis.

FINDINGS: A total of 16 documents were identified, all of which met Scott's criteria and none were excluded from the study. A total of six themes and 56 subthemes were extracted. The contents of all the documents were extracted under six themes of Veillard et al.'s health system stewardship framework. Overall, the results show that national documents place greater emphasis on the development of preventive healthcare and health promotion. Documents often focus on engaging NGOs and the families of people with disabilities and on intersectoral collaboration for knowledge production and the development of intersectoral knowledge networks. In terms of health system governance in line with prevailing values, documents are mainly focused on health system stewardship by the Ministry of Health and on evidence-based decision-making with the participation of target groups. Also, documents place more emphasis on upgrading the national infrastructure and increasing access to rehabilitation services.

CONCLUSION: In some areas of rehabilitation services, there is a gap between national documents, which reflects differences in priorities, approaches, resources, and instruments available to strengthen rehabilitation services at the national and international levels.}, } @article {pmid39468071, year = {2024}, author = {Li, JX and Wang, YH and Bair, H and Hsu, SB and Chen, C and Wei, JC and Lin, CJ}, title = {Reply to: mRNA COVID-19 vaccinations are not associated with RVO development 21 days and 12 weeks after vaccination.}, journal = {NPJ vaccines}, volume = {9}, number = {1}, pages = {203}, pmid = {39468071}, issn = {2059-0105}, abstract = {We appreciate your interest in our study. This study contrasts with Dorney et al.'s focus on the first 21 days. We conducted a re-analysis regarding selection bias and found consistent results. Our research highlights the elevated risk of retinal vascular occlusion after vaccination, which can last up to two years. We also discussed the differences in study design and the effects of different vaccine brands.}, } @article {pmid39467007, year = {2025}, author = {Jane, K and Wood, D and Gallagher, K and Livermore, P and Shoemark, H and Robert, G}, title = {Parents' experiences of psychotherapeutic support on the neonatal unit: A mixed methods systematic review to inform intervention development for a multicultural population.}, journal = {Nursing in critical care}, volume = {30}, number = {3}, pages = {e13194}, pmid = {39467007}, issn = {1478-5153}, support = {//National Institute for Health and Care Research/ ; }, mesh = {Humans ; *Parents/psychology ; *Intensive Care Units, Neonatal ; Infant, Newborn ; *Cultural Diversity ; *Psychotherapy/methods ; Intensive Care, Neonatal/psychology ; *Social Support ; }, abstract = {BACKGROUND: Parents of infants admitted to neonatal intensive care require support to minimize the impact on their mental health and to encourage engagement with their infants to support infant neurodevelopment. Many interventions aim to address this need, but there is a lack of research considering the accessibility of these for a multicultural population.

AIM: To systematically identify sources of psychotherapeutic support available for parents with infants admitted to neonatal care (NNU, neonatal intensive care unit [NICU] and special care units), assess their accessibility and acceptability and identify challenges and facilitators.

STUDY DESIGN: Six electronic databases with no restrictions on language or date were used to identify relevant studies following Preferred Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. Publications were included in the review if they reviewed parent experience of an intervention actively in place to support parent experience during the neonatal unit stay. Any studies where the intervention's primary aim was infant focused, such as developmental care, were excluded. All publications were quality-assessed using quality appraisal tools appropriate for their design type. Data were extracted line by line using Sekhon et al.'s theoretical acceptability framework and questionnaire.

RESULTS: A total of 3309 studies were found, of which 36 studies met the inclusion criteria. Included studies were published worldwide between 2000 and 2023 and explored 15 different interventions. Challenges for parental engagement were due to preconceived ideas about intervention requirements and parents' ability to participate in them. Timely information and providers' experience in delivering the intervention were reported to support engagement and as being valuable for enhancing participant knowledge. The emotional content of interventions was found to be challenging by parents across most studies. This was prominent in interventions designed to be carried out in a group format and where keepsakes were created. However, the value of these interventions was in reducing parents' feelings of isolation through increased social support and providing a starting point for conversations with wider family and friends about the family's neonatal experience. Participant demographics were poorly reported, with only two studies taking into consideration the ethicality of the intervention.

CONCLUSION: Poor reporting of participant demographics, and a focus on mothers as participants, means findings are not transferrable to the wider population of parents in neonatal units. Future studies should consider how to ensure that research and interventions are accessible to multicultural populations to improve the understanding of the acceptability of interventions. Better knowledge of neonates and the NNU setting amongst intervention providers could increase the accessibility of psychotherapeutic support for parents. Training for providers on how to manage sensitive conversations may also be beneficial to support parents during interventions.

The impact of neonatal admission on parental mental health is increasingly recognized and reported. Interventions have been developed to reduce the negative impact on the mental health of parents. There continue to be significant health inequalities as a result of many services not taking into account the acceptability and accessibility of interventions in this setting for their multicultural populations. This review highlights the need for better reporting of participant demographics in research and the inclusion of those seldom heard to ensure interventions are culturally, religiously and linguistically appropriate for multicultural populations.}, } @article {pmid39466802, year = {2024}, author = {Rasp, DM and Paternoster, FK and Kern, J and Schwirtz, A}, title = {Precise instruction and consideration of the vertical and horizontal force component increases validity and reliability of the 90:20 Isometric Posterior Chain Test.}, journal = {PloS one}, volume = {19}, number = {10}, pages = {e0312843}, pmid = {39466802}, issn = {1932-6203}, mesh = {Humans ; *Muscle Strength/physiology ; Reproducibility of Results ; *Hamstring Muscles/physiology ; Male ; Young Adult ; *Isometric Contraction/physiology ; Female ; Adult ; Torque ; }, abstract = {Hamstring injuries are associated with decreased hamstring strength. Matinlauri et al.'s 90:20 Isometric Posterior Chain Test (90:20 IPCT) efficiently assesses hamstring strength, but has not been validated so far. Furthermore, their rather unprecise original instruction allows high variability in test execution. We added a new instruction and variables and examined, whether this measure leads to increased reliability and validity. We assessed hamstring strength of 23 sport students via the 90:20 IPCT under the original instruction, to exert vertical force, and our new instruction, to exert vertical and horizontal force. Instead of only using bare vertical force as variable under the original (Fz_V) and our new instruction (Fz_VH), we also calculated the resultant force (Fres_VH) and the applied torque onto the force place (M_F_ortho_VH). To test for validity, we correlated the outcome variables with peak torque of gold standard dynamometry. Furthermore, we measured muscle activities of the mm. rectus femoris, biceps femoris, semitendinosus, and gluteus maximus under our new instruction and compared them to those under the original variable (Fz_V) via one sample t-tests. To evaluate reliability, tests were repeated on two separate days, for which we calculated intra class correlation coefficients (ICCs) and coefficients of variation (CVs). Our new instruction and variables (Fz_VH, Fres_VH, M_F_ortho_VH) showed better validity (mean r = 0.77, r = 0.81, and r = 0.85) and equally good or better reliability (ICCs: 0.87, 0.89, and 0.94; CVs: 4.7%, 4.1%, and 4.7%) than the original instruction and variable (Fz_V) (mean r = 0.70; ICC: 0.91; CV: 5.6%). There were no differences in muscle activities between the variables and instructions of the 90:20 IPCT. We recommend our new instruction and the applied torque onto the force plate as it makes the 90:20 IPCT a more reliable and valid tool to assess hamstring strength.}, } @article {pmid39466016, year = {2024}, author = {Joyce, M and Wrigley, C and Kells, M and Suarez, C and Flynn, D and Spillane, A and Owens, A}, title = {The Questionnaire for Suicidal Ideation (QSI): Psychometric Properties of a Brief Tool Measuring Suicidal Ideation in Adult and Adolescent Clinical Populations.}, journal = {Psicothema}, volume = {36}, number = {4}, pages = {361-368}, doi = {10.7334/psicothema2023.252}, pmid = {39466016}, issn = {1886-144X}, mesh = {Humans ; *Suicidal Ideation ; Adolescent ; Male ; Female ; *Psychometrics ; Adult ; Young Adult ; Surveys and Questionnaires ; Middle Aged ; Reproducibility of Results ; Self Report ; }, abstract = {BACKGROUND: Identifying accurate methods of assessing suicidal ideation has important implications. The lack of a universal definition of suicidal ideation has complicated measurement efforts. This study details the development of a brief self-report measure of suicidal ideation which specifically focuses on thoughts of suicide.

METHOD: The Questionnaire for Suicidal Ideation (QSI) was developed by collating items from three existing measures of suicidal ideation. Items explicitly describing acts or behaviours were removed and Posner et al.'s (2007) definition of suicidal ideation was applied to the remaining items. The final questionnaire consisted of 6 items. Participants were adults (n = 192) and adolescents (n = 152) attending community mental health services in the Irish public health service.

RESULTS: The QSI demonstrated excellent reliability in adult (α = .91) and adolescent (= .90) samples. Exploratory factor analysis produced a one-factor solution explaining 70% and 66% of the variance in adult and adolescent samples respectively. Evidence of relation with other variables was demonstrated with strong correlations between the QSI and measures of depression, hopelessness and borderline symptoms (r = .48 - .68).

CONCLUSIONS: The results suggest that the QSI may be a reliable and valid method of assessing suicidal ideation in clinical populations.}, } @article {pmid39463451, year = {2024}, author = {Li, Z and Duan, Y and Yang, X}, title = {Linking Thermal Conductivity to Equations of State Using the Residual Entropy Scaling Theory.}, journal = {Industrial & engineering chemistry research}, volume = {63}, number = {42}, pages = {18160-18175}, pmid = {39463451}, issn = {0888-5885}, abstract = {In recent years, the application of the residual entropy scaling (RES) method for modeling transport properties has become increasingly prominent. Based on Yang et al. (Ind. Eng. Chem. Res. 2021, 60, 13052) in modeling the thermal conductivity of refrigerants, we present here an RES model that extends Yang et al.'s approach to a wider range of pure fluids and their mixtures. All fluids available in the REFPROP 10.0 software, i.e., those with reference equations of state (EoS), were studied. A total of 71,554 experimental data of 125 pure fluids and 16,702 experimental data of 164 mixtures were collected from approximately 647 references, mainly based on the NIST ThermoData Engine (TDE) database 10.1. As a result, over 68.2% (corresponding to the standard deviation of a normal distribution) of the well-screened experimental data agree with the developed RES model within 3.1% and 4.6% for pure fluids and mixtures, respectively. Comparative analysis against the various models implemented in the REFPROP 10.0 (one of the state-of-the-art software packages for thermophysical property calculations) reveals that our RES model demonstrates analogous statistical agreement with experimental data yet with much fewer parameters. Regarding the average absolute value of the relative deviation (AARD) from experimental values to model predictions, the developed RES model shows a smaller or equal AARD for 74 pure fluids out of 125 and 76 mixtures out of 164. Besides, a detailed examination of the impact of the critical enhancement term on mixture calculations was conducted. To use our model easily, a software package written in Python is provided in the Supporting Information.}, } @article {pmid39457678, year = {2024}, author = {Forrest, BD and Goyal, NA and Fleming, TR and Bracci, PM and Brett, NR and Khan, Z and Robinson, M and Azhir, A and McGrath, M}, title = {The Effectiveness of NP001 on the Long-Term Survival of Patients with Amyotrophic Lateral Sclerosis.}, journal = {Biomedicines}, volume = {12}, number = {10}, pages = {}, pmid = {39457678}, issn = {2227-9059}, support = {01//Neuvivo, Inc./ ; }, abstract = {BACKGROUND/OBJECTIVES: The aim of this study was to estimate the effect of a 6 months' treatment course of the innate immune modulator NP001 (a pH-adjusted intravenous formulation of purified sodium chlorite), on disease progression, as measured by overall survival (OS) in patients with amyotrophic lateral sclerosis.

METHODS: Blinded survival data were retrospectively collected for 268 of the 273 patients who had participated in two phase 2 placebo-controlled clinical trials of NP001 (ClinicalTrials.gov: NCT01281631 and NCT02794857) and received at least one dose of either 1 mg/kg or 2 mg/kg of NP001 as chlorite based on actual body weight, or placebo. Kaplan-Meier methods were used on the intent-to-treat population to estimate survival probabilities.

RESULTS: In the overall population, the median OS was 4.8 months (2.7 years [95% CI: 2.3, 3.5] in the 2 mg/kg NP001group and 2.3 years [95% CI: 1.8, 2.9] in the placebo group). Hazard ratio (HR): 0.77 (95% CI: 0.57, 1.03), p = 0.073. Among patients aged ≤ 65 years, the median OS for the 2 mg/kg NP001 group was 10.8 months (3.3 years [95% CI: 2.4, 3.8] in the 2 mg/kg NP001 group and 2.4 years [95% CI: 1.7, 3.3] in the placebo group). HR: 0.69 (95% CI: 0.50, 0.95). No differences were observed in the 1 mg/kg NP001 group or in patients aged > 65 years.

CONCLUSIONS: The findings from this study suggest that a 6 months' treatment course of NP001 resulted in a 4.8-month increase in overall survival in patients with ALS. The findings from this study indicate that targeting inflammation associated with the innate immune system may provide a pathway for new therapeutic options for the treatment of ALS.}, } @article {pmid39457470, year = {2024}, author = {Trabacca, A and Ferrante, C and Oliva, MC and Fanizza, I and Gallo, I and De Rinaldis, M}, title = {Update on Inherited Pediatric Motor Neuron Diseases: Clinical Features and Outcome.}, journal = {Genes}, volume = {15}, number = {10}, pages = {}, pmid = {39457470}, issn = {2073-4425}, support = {2024//The Italian Health Ministry - Ricerca Corrente/ ; }, mesh = {Humans ; *Motor Neuron Disease/genetics/pathology ; Child ; Mutation ; Muscular Atrophy, Spinal/genetics/pathology/diagnosis ; Exome Sequencing ; }, abstract = {BACKGROUND: Inherited pediatric motor neuron diseases (MNDs) are a group of neurodegenerative disorders characterized by the degeneration of motor neurons in the brain and the spinal cord. These diseases can manifest as early as infancy and originate from inherited pathogenic mutations in known genes. Key clinical features of MNDs include muscle weakness, hypotonia, and atrophy due to the degeneration of lower motor neurons or spasticity, hypertonia, and hyperreflexia caused by upper motor neuron dysfunction. The course of the disease varies among individuals and is influenced by the specific subtype.

METHODS: We performed a non-systematic, narrative clinical review, employing a systematic methodology for the literature search and article selection to delineate the features of hereditary pediatric motor neuron diseases.

RESULTS: The growing availability of advanced molecular testing, such as whole-exome sequencing (WES) and whole-genome sequencing (WGS), has expanded the range of identified genetic factors. These advancements provide insights into the genetic complexity and underlying mechanisms of these disorders. As more MND-related genes are discovered, the accumulating genetic data will help prioritize promising candidate genes for future research. In some cases, targeted treatments based on specific genetic mechanisms have already emerged, underscoring the critical role of early and timely diagnosis in improving patient outcomes. Common MNDs include amyotrophic lateral sclerosis, spinal muscular atrophy, and bulbar spinal muscular atrophy.

CONCLUSION: This narrative clinical review covers the clinical presentation, genetics, molecular features, and pathophysiology of inherited pediatric MNDs.}, } @article {pmid39456004, year = {2024}, author = {Reihani, H and Zare, F and Moosavi, M and Amini, M}, title = {The correlation between medical students' clinical dishonesty, psychological distress, and moral intelligence.}, journal = {BMC medical education}, volume = {24}, number = {1}, pages = {1217}, pmid = {39456004}, issn = {1472-6920}, mesh = {Humans ; *Students, Medical/psychology ; Female ; Male ; Cross-Sectional Studies ; *Morals ; Psychological Distress ; Young Adult ; Surveys and Questionnaires ; Professional Misconduct/psychology ; Adult ; Stress, Psychological ; Emotional Intelligence ; }, abstract = {INTRODUCTION: Clinical dishonesty is one of the components of academic dishonesty that deals with the unprofessional behavior of students in hospital and clinic environments (medical students, nursing students, etc.). Psychological distress and low moral intelligence among students can be known as predisposing factors in performing dishonest clinical behaviors. The present research addresses a gap in the scientific literature by investigating dishonest behavior among medical students.

METHODS: This cross-sectional study examined medical students' clinical dishonesty, psychological distress, and moral intelligence. Rafati et al.'s questionnaire was used to investigate clinical dishonesty, Kessler's Psychological Distress Questionnaire (K6) was used for psychological distress, and Lenik and Keil's (2005) questionnaire was used to determine moral intelligence. Cochran's formula was used to calculate the sample size and the simple random sample (SRS) method was used for sampling. Data were statistically analyzed in SPSS version 27 (SPSS Inc., Chicago, IL, United States). a P-value less than 0.05 was considered significant.

RESULTS: 317 medical students were included in this study, of which 176 (55.5%) were male and 141 (44.5%) were female. We found a direct and significant statistical correlation between clinical dishonesty and students' distress (Correlation Coefficient: 0.162, P-value < 0.001). In addition, there was a statistically significant inverse correlation between clinical dishonesty and moral intelligence (Correlation Coefficient: -0.241, P-value: 0.004). Moreover, there was a higher rate of clinical dishonesty among senior medical students (P-value < 0.001). Moreover, the most dishonest clinical behaviors are as follows: [1] Disclosure of patient information in public or with non-medical personnel (76%), Incorrect examination of vital signs and physical examinations (69.4%), Not reporting incidents or errors of others involving patients (41.6%).

CONCLUSION: Finally, most students have experienced engaging in at least one clinically dishonest behavior. Such actions increase with the progress of the educational level so that it reaches its peak at the internship stage. Moral intelligence is a learnable concept, and mental distress also has its own treatments. Therefore, improving these two factors can reduce clinical dishonesty among medical students.}, } @article {pmid39454309, year = {2025}, author = {McKechnie, T and Bogdan, RM and Brennan, K and Shi, V and Grewal, S and Eskicioglu, C and Farooq, A and Patel, S}, title = {Fragility index for extended prophylaxis following abdominopelvic surgery: A methodological survey.}, journal = {American journal of surgery}, volume = {239}, number = {}, pages = {116020}, doi = {10.1016/j.amjsurg.2024.116020}, pmid = {39454309}, issn = {1879-1883}, mesh = {Humans ; *Abdomen/surgery ; *Pelvis/surgery ; *Postoperative Complications/epidemiology/etiology/prevention & control ; Randomized Controlled Trials as Topic ; Venous Thromboembolism/epidemiology/etiology/prevention & control ; }, abstract = {BACKGROUND: Fragility Index (FI) is increasingly used to assess robustness of statistically significant p-values reported in randomized controlled trials (RCTs). FI represents the lowest number of non-events changed to events that would make study findings non-significant. This methodological survey was designed to assess the fragility of the evidence for extended VTEp following major abdominopelvic surgery.

METHODS: MEDLINE, Embase, and CENTRAL were searched from inception to November 2023. RCTs with parallel, double-armed, superiority design comparing extended VTEp for patients undergoing major abdominopelvic surgery to controls with at least one statistically significant dichotomous outcome were included. Walsh et al.'s method of calculating FI was utilized.

RESULTS: After review of 611 citations, 6 RCTs were identified with 12 statistically significant outcomes between groups. The mean number of patients randomized per RCT was 419 (SD 176). The median FI was 1.5 (range: 1-4). The number of patients lost to follow-up was greater than the FI for 10/12 (83.3 ​%) outcomes.

CONCLUSIONS: Statistically significant differences reported in RCTs evaluating extended VTEp following major abdominopelvic surgery are not robust.}, } @article {pmid39454052, year = {2025}, author = {Nicolaou, N and Valentino, M and Nicolaou, D}, title = {Comment on Dutta Majumder et al.'s 2019 'Ocular Syphilis: An Update'.}, journal = {Ocular immunology and inflammation}, volume = {33}, number = {3}, pages = {497-498}, doi = {10.1080/09273948.2024.2414232}, pmid = {39454052}, issn = {1744-5078}, mesh = {Humans ; *Eye Infections, Bacterial/diagnosis/microbiology/drug therapy ; *Syphilis/diagnosis/drug therapy/microbiology ; }, abstract = {The article 'Ocular Syphilis: An Update (2019)' provides a thorough review of the challenges in diagnosing ocular syphilis. However, our research on 'Dermatological and Ocular Manifestations of Syphilis,' identifies a significant gap in both literature and clinical practice: the lack of recognition of dermatological signs during ophthalmological assessments. Ocular syphilis often mimics other conditions and can remain undiagnosed for months or years. Detecting dermatological signs, such as the characteristic palmar rash of secondary syphilis and extragenital chancres, could prompt earlier investigation and serological testing, reducing unnecessary diagnostic workups and inappropriate management. Early recognition would facilitate timely administration of Penicillin G, helping prevent vision loss, which is often reversible with prompt treatment. We urge Ocular Immunology and Inflammation to highlight the importance of incorporating dermatological assessments in future ocular syphilis publications to improve diagnostic protocols and patient outcomes.}, } @article {pmid39450245, year = {2024}, author = {Schlunk, S and Byram, B}, title = {Expanding generalized contrast-to-noise ratio into a clinically relevant measure of lesion detectability by considering size and spatial resolution.}, journal = {Journal of medical imaging (Bellingham, Wash.)}, volume = {11}, number = {5}, pages = {057001}, pmid = {39450245}, issn = {2329-4302}, abstract = {PURPOSE: Early image quality metrics were often designed with clinicians in mind, and ideal metrics would correlate with the subjective opinion of practitioners. Over time, adaptive beamformers and other post-processing methods have become more common, and these newer methods often violate assumptions of earlier image quality metrics, invalidating the meaning of those metrics. The result is that beamformers may "manipulate" metrics without producing more clinical information.

APPROACH: In this work, Smith et al.'s signal-to-noise ratio (SNR) metric for lesion detectability is considered, and a more robust version, here called generalized SNR (gSNR), is proposed that uses generalized contrast-to-noise ratio (gCNR) as a core. It is analytically shown that for Rayleigh distributed data, gCNR is a function of Smith et al.'s C ψ (and therefore can be used as a substitution). More robust methods for estimating the resolution cell size are considered. Simulated lesions are included to verify the equations and demonstrate behavior, and it is shown to apply equally well to in vivo data.

RESULTS: gSNR is shown to be equivalent to SNR for delay-and-sum (DAS) beamformed data, as intended. However, it is shown to be more robust against transformations and report lesion detectability more accurately for non-Rayleigh distributed data. In the simulation included, the SNR of DAS was 4.4 ± 0.8 , and minimum variance (MV) was 6.4 ± 1.9 , but the gSNR of DAS was 4.5 ± 0.9 , and MV was 3.0 ± 0.9 , which agrees with the subjective assessment of the image. Likewise, the DAS 2 transformation (which is clinically identical to DAS) had an incorrect SNR of 9.4 ± 1.0 and a correct gSNR of 4.4 ± 0.9 . Similar results are shown in vivo.

CONCLUSIONS: Using gCNR as a component to estimate gSNR creates a robust measure of lesion detectability. Like SNR, gSNR can be compared with the Rose criterion and may better correlate with clinical assessments of image quality for modern beamformers.}, } @article {pmid39450104, year = {2024}, author = {Wu, S}, title = {Potential differences in ephedrine requirements between left lateral and right lateral decubitus positions during neuraxial anesthesia for cesarean delivery.}, journal = {Frontiers in medicine}, volume = {11}, number = {}, pages = {1454681}, pmid = {39450104}, issn = {2296-858X}, abstract = {The recent article by Wen et al., published in PLOS ONE, titled "Effects of neuraxial anesthesia in sitting and lateral positions on maternal hemodynamics in cesarean section: A systematic review and meta-analysis," caught my attention. In their study, the authors observed the effects of neuraxial anesthesia in sitting and lateral positions on maternal hemodynamics during cesarean section. Given the anatomical differences between the left and right sides of the body, which could result in differences in maternal hemodynamics and vasopressor requirements during neuraxial anesthesia for cesarean delivery, I was intrigued by the idea of further dividing the lateral position data from Wen et al.'s study into three subgroups: "left lateral position," "right lateral position," and "not mentioned" (where the included original study did not mention the lateral position) for a subgroup analysis. It seems to be more rigorous, the subgroup analysis revealed that the usage rate of ephedrine support was 1.42 times higher for parturients in the right lateral position compared to those in the sitting position. This finding supports our recommendation to distinguish between left and right lateral decubitus positioning in neuraxial anesthesia for cesarean delivery. But in contrast, no significant difference was observed between the sitting and lateral positions in terms of the number of parturients requiring ephedrine in Wen et al.'s. Given the limited research on the right-lateral position and its hemodynamic effects, further studies are needed to explore its clinical applications. Future research should also focus on conducting larger trials with greater sample sizes to evaluate the long-term neonatal outcomes associated with varying maternal positions. Additionally, researchers should conduct subgroup analyses that separate the left- and right-lateral positions to provide clearer guidance for anesthesiologists.}, } @article {pmid39449555, year = {2024}, author = {Hagan, KE and Christensen Pacella, KA}, title = {Balancing Objective Markers and Subjective Experience in Eating Disorder Diagnoses: Commentary on Dang et al. (2024).}, journal = {The International journal of eating disorders}, volume = {57}, number = {10}, pages = {2049-2052}, pmid = {39449555}, issn = {1098-108X}, support = {K12 AR084233/AR/NIAMS NIH HHS/United States ; K12AR084233/NH/NIH HHS/United States ; }, mesh = {Humans ; *Feeding and Eating Disorders/diagnosis/psychology ; *Diagnostic and Statistical Manual of Mental Disorders ; Feeding Behavior/psychology ; }, abstract = {The results of Dang et al.'s recent systematic review and meta-analysis suggested that individuals diagnosed with other specified feeding or eating disorder (OSFED) and those diagnosed with specified eating disorders (EDs, such as bulimia nervosa) endorse similar, elevated levels of ED-related cognitions (but not behaviors). The DSM has traditionally conceptualized EDs primarily as disturbances in eating behavior, and the diagnostic boundaries for EDs are based on objective markers, such as behavioral frequencies and weight. Although focusing on objective markers for ED diagnoses and severity indices has advantages (e.g., clinical communication, measurement), pitfalls include diagnostic migration and low emphasis on ED cognitions. Dang et al.'s findings provide a basis for rethinking DSM's conceptualization of EDs as primarily behavioral. This commentary discusses the potential merits and challenges of emphasizing subjective cognitions when assigning ED diagnoses. We explore how objective markers (e.g., behavioral frequency, weight) and subjective experience (e.g., fear of weight gain) may be balanced to improve the clinical utility of ED diagnoses. In all, research that more deeply phenotypes the subjective experiences of people with EDs across contexts, identities, and cultures will enrich our understanding of eating pathology and may inform diagnostic revisions.}, } @article {pmid39449549, year = {2024}, author = {Keel, PK}, title = {Guidelines for Rigorous and Reproducible Research on Other Specified Feeding or Eating Disorder: Commentary on Dang et al. (2024).}, journal = {The International journal of eating disorders}, volume = {57}, number = {10}, pages = {2041-2044}, doi = {10.1002/eat.24262}, pmid = {39449549}, issn = {1098-108X}, support = {R01MH126990/MH/NIMH NIH HHS/United States ; R01MH126990/MH/NIMH NIH HHS/United States ; }, mesh = {Humans ; *Feeding and Eating Disorders/diagnosis ; Diagnostic and Statistical Manual of Mental Disorders ; Anorexia Nervosa/diagnosis ; Practice Guidelines as Topic ; }, abstract = {Dang et al.'s review concludes that atypical anorexia nervosa (atypical AN), purging disorder (PD), and night eating syndrome (NES) are clinically significant and severe eating disorders (EDs). However, findings are unlikely to alter their status in future editions of the DSM due to limitations in the literature to date. Guidelines are offered to promote rigorous and reproducible research on other specified feeding or eating disorder OSFED. First, published research diagnostic criteria for atypical AN, PD, and NES should be consistently used to ensure findings across studies reflect the same conditions. Second, operational definitions are recommended for "recurrent" as at least twice within a 3-month period, minimum duration as at least 1 month, and "significant weight loss" as >5% BMI reduction within 1 month. Third, Thomas's and Gydus's trumping scheme for differential diagnosis of OSFED subcategories is endorsed but should prioritize identifying treatment targets based on medical morbidity over mirroring existing diagnostic algorithms. Fourth, a systematic approach for establishing clinical significance is recommended that explicitly notes medical risk associated with malnutrition, purging and nonpurging behaviors, and relevance of marked distress related to binge eating and body image disturbance. Adoption of these guidelines will facilitate necessary research on clinical utility.}, } @article {pmid39449539, year = {2024}, author = {Claudino, AM and Hay, PJ}, title = {Taking a Global View of the OSFED Category From Inside and Outside the DSM-5: Comment on Dang et al. 2024.}, journal = {The International journal of eating disorders}, volume = {57}, number = {10}, pages = {2045-2048}, doi = {10.1002/eat.24267}, pmid = {39449539}, issn = {1098-108X}, mesh = {Humans ; *Diagnostic and Statistical Manual of Mental Disorders ; *Feeding and Eating Disorders/diagnosis/classification ; International Classification of Diseases ; }, abstract = {This Commentary discusses the findings of Dang et al.'s systematic review and metanalysis on the "Other Specified Feeding or Eating Disorder" (OSFED) category in the context of current conceptualizations and main international diagnostic schemes of classification, the DSM-5 and the ICD-11. The aim to reduce less specified eating disorder categories in these classifications has not been completely achieved and OSFED cases remain prevalent. Different definitions of OSFED contribute to difficulties in study selection and limitation of data aggregation in metanalysis, highlighting the need for improving methodologies for studying OSFED subtypes. Although use of either the DSM-5 or ICD-11 scheme concurs with Dang et al.'s main finding that OSFED comprises categories of similar clinical significance to the recognized eating disorders, the ICD-11 includes more people with anorexia nervosa, bulimia nervosa, or binge-eating disorder who would receive a DSM-5 OSFED diagnosis. This may have impacts for epidemiological studies of distribution as well as for identification and treatment of the individual. We support that before creating new eating disorder categories, consideration be given to also broadening current DSM-5 criteria. This approach may result in fewer OSFED subtypes needing elevation to distinct categories, potentially limiting these to just purging disorder and night eating syndrome.}, } @article {pmid39449110, year = {2024}, author = {Yang, F and Wang, P and Tang, Y and Song, M and Jing, J and Lu, G and Wee, B}, title = {Family caregivers' administration of medications at the end-of-life in China: a qualitative study.}, journal = {BMC palliative care}, volume = {23}, number = {1}, pages = {248}, pmid = {39449110}, issn = {1472-684X}, support = {IGS202004//The first batch of Independent Projects from the Tsinghua Institute for Governance Studies/ ; 2022THZWJC27//Tsinghua University for Initiative Scientific Research Program/ ; }, mesh = {Humans ; *Caregivers/psychology ; China ; *Qualitative Research ; Male ; *Terminal Care/methods/standards/psychology ; Female ; Middle Aged ; Adult ; Aged ; Interviews as Topic/methods ; }, abstract = {BACKGROUND: Effective medication management is crucial for ensuring timely pain and symptom control at the end of life. Dying in pain is a major concern for patients, yet some find less effective pain control at home. Family caregivers (FCGs) play a vital role in managing pain and symptom control for dying patients. However, the experience of administering medications at home for terminal-stage patients has not been widely recognized or understood. Our study aimed to explore the experiences of FCGs in administering medications to adult dying patients.

METHODS: We conducted a directed content analysis of data from 73 semi-structured interviews with FCGs across 19 Chinese provinces from 2021 to 2023. FCGs were recruited through the Voluntary Cooperative Network Research. We asked, "Could you recall the end-of-life care process for the patients?" We aligned the themes with the five issues identified by Wilson et al. (2018): administration, organizational skills, empowerment, relationships, and support.

RESULTS: FCGs in China exhibit concerns about over-engagement and empowerment in medication administration, concealing medication information from the patient, and medication accessibility. FCGs faced significant challenges in accurately identifying and addressing pain and symptoms, determining appropriate dosages, accessing effective medications, and managing the emotional stress associated with potential medication errors. Financial burden, medication regulatory restrictions, geographical inequality, and travel restrictions during COVID impeded patients and FCGs from accessing medication. A culturally specific finding is the use of alternative medicine at the end of life.

CONCLUSION: Our findings build upon Wilson et al.'s framework and extend their insights on empowerment, highlighting the need for policies to support home-based palliative care professionals in training FCGs for effective medication administration.}, } @article {pmid39441804, year = {2024}, author = {Khezri, SF and Ebrahimi, A and Eslahchi, C}, title = {Target controllability: a feed-forward greedy algorithm in complex networks, meeting Kalman's rank condition.}, journal = {Bioinformatics (Oxford, England)}, volume = {40}, number = {11}, pages = {}, pmid = {39441804}, issn = {1367-4811}, mesh = {*Algorithms ; Humans ; Computational Biology/methods ; }, abstract = {MOTIVATION: The concept of controllability within complex networks is pivotal in determining the minimal set of driver vertices required for the exertion of external signals, thereby enabling control over the entire network's vertices. Target controllability further refines this concept by focusing on a subset of vertices within the network as the specific targets for control, both of which are known to be NP-hard problems. Crucially, the effectiveness of the driver set in achieving control of the network is contingent upon satisfying a specific rank condition, as introduced by Kalman. On the other hand, structural controllability provides a complementary approach to understanding network control, emphasizing the identification of driver vertices based on the network's structural properties. However, in structural controllability approaches, the Kalman condition may not always be satisfied.

RESULTS: In this study, we address the challenge of target controllability by proposing a feed-forward greedy algorithm designed to efficiently handle large networks while meeting the Kalman controllability rank condition. We further enhance our method's efficacy by integrating it with Barabasi et al.'s structural controllability approach. This integration allows for a more comprehensive control strategy, leveraging both the dynamical requirements specified by Kalman's rank condition and the structural properties of the network. Empirical evaluation across various network topologies demonstrates the superior performance of our algorithms compared to existing methods, consistently requiring fewer driver vertices for effective control. Additionally, our method's application to protein-protein interaction networks associated with breast cancer reveals potential drug repurposing candidates, underscoring its biomedical relevance. This study highlights the importance of addressing both structural and dynamical aspects of network controllability for advancing control strategies in complex systems.

The source code is available for free at:Https://github.com/fatemeKhezry/targetControllability.}, } @article {pmid39430798, year = {2025}, author = {Bicknell, K and Bushong, W and Tanenhaus, MK and Jaeger, TF}, title = {Maintenance of subcategorical information during speech perception: revisiting misunderstood limitations.}, journal = {Journal of memory and language}, volume = {140}, number = {}, pages = {}, pmid = {39430798}, issn = {0749-596X}, support = {R01 HD073890/HD/NICHD NIH HHS/United States ; R01 HD075797/HD/NICHD NIH HHS/United States ; T32 DC000035/DC/NIDCD NIH HHS/United States ; }, abstract = {Accurate word recognition is facilitated by context. Some relevant context, however, occurs after the word. Rational use of such "right context" would require listeners to have maintained uncertainty or subcategorical information about the word, thus allowing for consideration of possible alternatives when they encounter relevant right context. A classic study continues to be widely cited as evidence that subcategorical information maintenance is limited to highly ambiguous percepts and short time spans (Connine et al., 1991). More recent studies, however, using other phonological contrasts, and sometimes other paradigms, have returned mixed results. We identify procedural and analytical issues that provide an explanation for existing results. We address these issues in two reanalyses of previously published results and two new experiments. In all four cases, we find consistent evidence against both limitations reported in Connine et al.'s seminal work, at least within the classic paradigms. Key to our approach is the introduction of an ideal observer framework to derive normative predictions for human word recognition expected if listeners maintain and integrate subcategorical information about preceding speech input rationally with subsequent context. We test these predictions in Bayesian mixed-effect analyses, including at the level of individual participants. While we find that the ideal observer fits participants' behavior better than models based on previously proposed limitations, we also find one previously unrecognized aspect of listeners' behavior that is unexpected under any existing model, including the ideal observer.}, } @article {pmid39425480, year = {2025}, author = {Wu, YC and Wei, LC}, title = {Applying global lessons from limerick: Insights for Taiwan's drug policy development.}, journal = {The International journal of health planning and management}, volume = {40}, number = {1}, pages = {254-256}, doi = {10.1002/hpm.3862}, pmid = {39425480}, issn = {1099-1751}, abstract = {This letter responds to Duopah et al.'s study on illicit drug use in Limerick City, drawing parallels with Taiwan's experiences in drug policy development and highlighting lessons from other countries with advanced harm reduction policies, including Portugal and Switzerland. The application of Kingdon's multiple streams model is used to analyse cross-cultural policy development. Taiwan's shift from punitive to health-oriented strategies, such as supervised injection facilities and rehabilitation programs, is explored. This letter emphasises the challenges of stakeholder engagement, particularly in integrating the perspectives of people who use drugs, and discusses the broader implications for international policy adaptation, especially in countries with similar health system challenges. Taiwan's development of multi-tiered interventions and integrated care models serves as an example of evidence-based policymaking. These insights highlight the potential for global cross-cultural learning in drug policy development.}, } @article {pmid39425065, year = {2024}, author = {Jones, AT and Tremblay, É and Costeux, AL and Strus, JA and Barcket, A}, title = {What tools are available to assess climate and environmental health impacts on perinatal families with an equity lens? A rapid review of the Canadian context.}, journal = {BMC pregnancy and childbirth}, volume = {24}, number = {1}, pages = {680}, pmid = {39425065}, issn = {1471-2393}, mesh = {Humans ; Canada ; *Climate Change ; Female ; Pregnancy ; *Perinatal Care ; *Environmental Health ; Health Equity ; Social Determinants of Health ; }, abstract = {OBJECTIVES: This rapid review is designed to identify existing tools in the Canadian literature that assess the impacts of climate change on the health of perinatal families, particularly those who are equity-denied. Addressing the needs of equity-denied perinatal populations in the face of climate change is crucial to promoting equitable and inclusive perinatal care in Canada.

METHODS: Rapid review methodology was selected to provide evidence in a timely and cost-effective manner. PubMed/MEDLINE and gray literature (Google and Google Scholar) were searched for English and French papers published from 2013 onward. The original research question, focused on climate change and health, yielded very few relevant results. Therefore, the search was broadened to include environmental health. Garrity et al.'s (J Clin Epidemiol 130:13-22, 2021) nine-stage process was used to identify 11 relevant papers, extract the relevant data, and complete the narrative synthesis.

SYNTHESIS: This review revealed a significant lack of tools for comprehensively assessing climate-health impacts on perinatal families and equity-denied perinatal families. While Canadian perinatal health screenings focus on equity via indicators of several social determinants of health (e.g., income, social support), they largely omit climate considerations. Environmental health factors are more commonly included but remain minimal.

CONCLUSION: Climate-health screening tools are lacking yet needed in routine perinatal healthcare. Given the seriousness of climate change, urgent engagement of health systems and healthcare workers is essential to help mitigate and adapt to climate-health challenges, particularly for perinatal families experiencing health inequities.}, } @article {pmid39423220, year = {2024}, author = {Ahmady, S and Khajeali, N and Kohan, N and Zarei, A and Biswas, B and Barzegar, M and Moghaddam, AK}, title = {Medical students' perception of mobile learning during COVID-19 in Iran: A national study.}, journal = {PloS one}, volume = {19}, number = {10}, pages = {e0308248}, pmid = {39423220}, issn = {1932-6203}, mesh = {Humans ; *COVID-19/epidemiology/psychology ; *Students, Medical/psychology ; Iran/epidemiology ; Cross-Sectional Studies ; Male ; Female ; Surveys and Questionnaires ; *Mobile Applications ; Adult ; Education, Distance/methods ; Young Adult ; SARS-CoV-2 ; Pandemics ; Learning ; Education, Medical/methods ; Perception ; }, abstract = {INTRODUCTION: Mobile learning has gained significant attention in medical education in recent years. The COVID-19 crisis has further accelerated its adoption. A lack of research on student perceptions of mobile learning during pandemics limits strategies for maintaining education during these times. This study examines the perceptions of medical students in Iran regarding the mobile learning during COVID-19. It is imperative that these perceptions are understood to optimize mobile learning effectiveness in medical education during disruptions.

METHOD: A cross-sectional study was done in 2022 among 785 medical students in Iran who spent summer semester. Convenience sampling was used to select the sample. We used Biswas et al.'s scale for measuring medical students' perceptions of mobile learning during pandemics. Face and content validity was determined by qualitative methods. Internal consistency was measured with Cronbach's Alpha (0.79). Data was collected through an online questionnaire. To analyze the data, descriptive and analytical statistics were conducted with SPSS software at a significance level of p<0.05.

RESULTS: In total, 1,200 medical students were asked to complete the survey, and 785 responded, resulting in a 65.4% response rate. Mobile learning has been embraced by majority of medical students, with Android devices being used the most frequently. They also have frequent access to the internet, and they rely on a wide range of apps and platforms for academic purposes. Students perceive mobile devices to be highly advantageous for improving subject knowledge (Mean = 4.71±0.58), accessing study materials (Mean = 4.44±0.75), and providing flexible learning opportunities (Mean = 4.40±0.79). Despite this, participants were less confident about the ability of mobile devices to assist with specific study problems (Mean = 3.12 ± 1.28), facilitate class discussions (Mean = 3.33 ± 1.38), and overcome screen size limitations (Mean = 3.32 ± 1.38).

CONCLUSION: Medical students in Iran have widely adopted mobile learning and perceive it as beneficial for acquiring knowledge, accessing material, and being flexible during COVID-19. M-learning's effectiveness in specific learning activities must be investigated in further research, and concerns regarding problem-solving, discussion facilitation, and screen size limitations should be addressed.}, } @article {pmid39415558, year = {2024}, author = {Tien, Y and Wei, LC}, title = {Expanding perspectives on figurative language processing in autism spectrum disorder: A commentary on Lampri et al.'s review.}, journal = {Autism research : official journal of the International Society for Autism Research}, volume = {17}, number = {11}, pages = {2194-2195}, doi = {10.1002/aur.3249}, pmid = {39415558}, issn = {1939-3806}, } @article {pmid39413998, year = {2025}, author = {Dinc, R and Ardic, N}, title = {Role of Potential Biomarkers in Aortic Aneurysms: Does It Hold Promise for Clinical Decision Making?.}, journal = {Annals of vascular surgery}, volume = {110}, number = {Pt A}, pages = {349-352}, doi = {10.1016/j.avsg.2024.07.128}, pmid = {39413998}, issn = {1615-5947}, mesh = {Humans ; *Aortic Aneurysm/surgery/diagnostic imaging/metabolism ; *Biomarkers/blood ; *Clinical Decision-Making ; *Predictive Value of Tests ; Prognosis ; Risk Factors ; }, abstract = {Aortic aneurysms (AAs) are a life-threatening disease with a mortality rate of up to 80% when they rupture. AA has a multifactorial etiology, including smoking, advanced age, and family history, and has multifaceted pathophysiological mechanisms underlying its formation, mainly including inflammation of the aortic wall, reduction of medial smooth muscle cells, and degradation of the extracellular matrix. It is also a progressive disease. Their treatments are limited to open surgical repair and endovascular aneurysm repair. There is no effective drug treatment. The diagnosis of AA is usually made as a result of a scan performed for another reason. There is no specific diagnostic and prognostic biomarker available, and great efforts are being made on this subject. These studies reveal that in the future, the causal pathophysiological mechanisms for the occurrence and progression of AA will be elucidated and some potential biomarkers will be adopted to facilitate clinical decision-making. This commentary provides a brief contribution to Teng et al.'s analysis of the causal influence between AA and immune-metabolic interactions, and eventually identification of biomarkers.}, } @article {pmid39405603, year = {2024}, author = {Asim, M}, title = {Decoding androgen receptor signalling: Genomic vs. non-genomic roles in prostate cancer.}, journal = {Neoplasia (New York, N.Y.)}, volume = {58}, number = {}, pages = {101066}, pmid = {39405603}, issn = {1476-5586}, mesh = {Animals ; Humans ; Male ; Androgens/metabolism ; Cell Proliferation ; Gene Expression Regulation, Neoplastic ; Genomics/methods ; *Prostatic Neoplasms/genetics/metabolism/pathology ; *Receptors, Androgen/metabolism/genetics ; Signal Transduction/genetics ; }, abstract = {The Androgen receptor (AR) is known to manifest the biological actions of male sex hormones. Androgens are now known to exert a multitude of responses, sometimes contrasting, in physiological and pathological conditions. Several groups have attempted to explain the underlying mechanisms of these varying androgen responses, including the non-genomic actions of androgens. These actions lead to increased activity of pro-proliferative signal transduction pathways, resulting in rapid molecular effects that cannot be explained by the conventional model in which AR functions as a transcription factor to modulate target gene expression [1,2]. This spotlight article examines Safi et al.'s research on the androgen receptor (AR) in prostate cancer, revealing that low androgen levels drive proliferation via non-genomic mechanisms involving AR monomers, while high levels suppress growth through genomic actions with AR dimers. These findings challenge current paradigms and suggest novel therapeutic strategies targeting both AR forms, particularly focusing on the role of AR monomers in cancer progression and treatment resistance.}, } @article {pmid39402501, year = {2024}, author = {Madzimbe, P and Maart, S and Corten, L and Dambi, J}, title = {Participation of fathers and siblings in home rehabilitation programmes for children with neuro-developmental delay: a scoping review.}, journal = {BMC pediatrics}, volume = {24}, number = {1}, pages = {659}, pmid = {39402501}, issn = {1471-2431}, mesh = {Humans ; Child ; *Fathers/psychology ; *Developmental Disabilities/rehabilitation ; *Siblings/psychology ; Caregivers/psychology ; Home Care Services ; }, abstract = {BACKGROUND: The role of, and impact on, mothers caring for children with neuro-developmental delay (NDD) is well documented. However, the role of fathers and siblings in families of children with NDD remains significantly understudied, particularly in low- and middle-income countries (LMICs). There has been an increased call for holistic rehabilitation of children with NDD at the family level. This study aimed to explore the involvement of fathers and siblings in the home rehabilitation programmes of children with NDD.

METHODS: A scoping review was conducted using the Joanna Briggs Institute (JBI) Peters et al.'s methodology and reported according to Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines. Articles were retrieved from PUBMED, ScienceDirect, PsycINFO, SCOPUS, PEDro, and Google Scholar. Reference lists of relevant studies were also manually searched.

RESULTS: Thirty research articles were identified. Father and sibling participation in home-based rehabilitation and caregiving is low in LMICs compared to high-income countries due to economic factors and cultural beliefs. Reduced participation stresses mothers and reduces developmental outcomes in children with NDD.

CONCLUSIONS: This review highlights the need for rehabilitation professionals to encourage father and sibling participation in caregiving for children with NDD in home rehabilitation programmes.}, } @article {pmid39394531, year = {2024}, author = {Shaheen, S and Aiman, U and Haque, ZA and Azad, Z}, title = {"Navigating the complexities of low-Grade glioma treatment: insights into SBT I-125 and novel assessment tools".}, journal = {Neurosurgical review}, volume = {47}, number = {1}, pages = {788}, doi = {10.1007/s10143-024-03028-1}, pmid = {39394531}, issn = {1437-2320}, mesh = {Humans ; *Brachytherapy/methods ; *Brain Neoplasms/pathology/therapy ; *Glioma/pathology/therapy/radiotherapy ; Neoplasm Grading ; Treatment Outcome ; Systematic Reviews as Topic ; Meta-Analysis as Topic ; }, abstract = {Central nervous system tumors, classified by the WHO into four grades based on their aggressiveness, present significant challenges in treatment, particularly low-grade gliomas (LGGs) which, despite their slower growth, can progress to high-grade gliomas. Lucca B. Palavani and colleagues evaluated the efficacy and safety of SBT I-125 brachytherapy for LGMs in a systematic review and meta-analysis of 20 studies involving 988 patients. The analysis revealed an overall complication rate of 10%, with headaches and cyst formation being the most frequent issues. The five-year progression-free survival (PFS) rate was 66%, while the ten-year PFS rate was 30%, and the rate of malignant transformation was 26%. The mortality rate was 33%. Despite these findings, significant limitations were noted, including data insufficiencies, study heterogeneity, lack of randomized controlled trials, and potential publication bias. Inconsistencies in follow-up durations further hindered the evaluation of long-term efficacy and safety. Recent advancements in automated tumor assessment, such as Cheng et al.'s deep learning-based pipeline, are revolutionizing glioma management by enhancing the accuracy and consistency of tumor volume and RANO measurements. These innovations facilitate improved glioma grading, genetic mutation prediction, surgical planning, real-time intraoperative guidance, and histopathological analysis. Integrating such advanced tools into clinical practice can significantly enhance the precision and efficiency of glioma management. In conclusion, while SBT I-125 brachytherapy shows promise, concerns regarding safety and efficacy underscore the need for further research with standardized methodologies. Incorporating advanced automated assessment tools could improve treatment evaluation and patient outcomes.}, } @article {pmid39391178, year = {2024}, author = {Morris, C and Donovan, MT and Switzer, EJ}, title = {The Scope of Practice of Applied Behavior Analysis in State Licensure Laws.}, journal = {Behavior analysis in practice}, volume = {17}, number = {3}, pages = {773-782}, pmid = {39391178}, issn = {1998-1929}, abstract = {The scope of applied behavior analysis has historically been defined by behavior analytic publications like Baer et al., Journal of Applied Behavior Analysis, 1, 91, (1968). However, starting in 2009, state legislators began creating licensure laws for behavior analysts that formalized the scope of practice for applied behavior analysis (ABA) within the applicable states. The purpose of this study was twofold: (1) to evaluate the degree scope of practice statements found in state licensure laws aligned with the individual components of Baer et al.'s seven dimensions of ABA and the APBA Model Act and (2) to evaluate the consistency of the scope of practice statements across states. Each licensed state law was identified, and the section that outlined the scope of practice was isolated and coded. The results of this study identified varying degrees of alignment with the individual components of Baer et al.'s seven dimensions and the APBA Model Act, as well as inconsistencies in the scope of practice among states with licensure for ABA. The component scores of each content area will be discussed, along with the implications for practice.}, } @article {pmid39384637, year = {2024}, author = {Haque, ZA and Nazakat, K}, title = {"Revolutionizing retrosigmoid surgical precision: AI in free bone flap reconstruction".}, journal = {Neurosurgical review}, volume = {47}, number = {1}, pages = {768}, pmid = {39384637}, issn = {1437-2320}, mesh = {Humans ; *Artificial Intelligence ; *Free Tissue Flaps ; Microvascular Decompression Surgery/methods ; *Plastic Surgery Procedures/methods ; }, abstract = {Free bone flap reconstruction is essential to the retrosigmoid method of microvascular decompression (MVD) and can completely transform surgical methods worldwide. According to studies like Liao et al. (2023), 92.3% of patients report feeling better after receiving treatment. The study by Shize Li et al. emphasizes the affordability and accessibility of free bone flap reconstruction, demonstrating shorter recovery times, lower expenses, and similar rates of complications to those of conventional fixation techniques. With benefits like fewer headaches and a quicker recovery in the free bone flap group, their retrospective analysis of 189 patients showed no significant differences in hospital stay or complication rates between the fixed and unfixed bone flap groups.Despite these results, larger sample sizes and longer-term studies are needed to confirm these findings and address issues such as leakage of cerebrospinal fluid. Furthermore, adding Artificial Intelligence (AI) to this method may improve accuracy and results. AI has the potential to enhance MVD procedures and patient outcomes through its capacity to create 3D models, direct bone flap placement, and track postoperative progress. Standardizing AI's application in clinical practice still presents difficulties, though. In the end, even though Shize Li et al.'s research significantly advances the body of knowledge already in existence, more creativity and investigation are required to maximize free bone flap reconstruction in MVD.}, } @article {pmid39383331, year = {2024}, author = {Wessel, I and Lehmann, R and Wiechert, S}, title = {Two replications of Wiechert et al.'s (2023) online Think/No-Think study in undergraduate students.}, journal = {Memory (Hove, England)}, volume = {}, number = {}, pages = {1-11}, doi = {10.1080/09658211.2024.2412025}, pmid = {39383331}, issn = {1464-0686}, abstract = {The Think/No-Think (TNT) task examines the effects of attempts at suppressing particular stimuli. First, participants learn cue-target word pairs. Subsequently, they either recall (Think trials) or avoid thinking about targets whatsoever (No-Think trials) in response to cues. The critical finding is that No-Think targets are recalled less well than Baseline items (i.e., Suppression-Induced Forgetting; SIF). Wiechert et al.'s [(2023). Suppression-induced forgetting: A pre-registered replication of the think/no-think paradigm. Memory (Hove, England), 31(7), 989-1002] null-findings in Prolific workers using online video calls casted doubts on the robustness of the effect. We adapted their procedure in two replication studies testing undergraduate psychology students. The first study (N = 54) adapted Wiechert's procedure to an in-person laboratory setting using Same Probe (SP) recall and found evidence for SIF. Hypothesizing that an online test should yield SIF in undergraduates as well, study 2 replicated both the in-person laboratory (n = 54) and online (n = 54) procedures. The results suggested evidence for SIF in the in-lab setting, yet no evidence was observed in the online setting. As exploratory Bayesian analyses showed conclusive evidence for a null effect, this pattern of results does not imply that the in-lab and online settings actually differed. Yet, overall, the results cast doubts on the generalisability of the SIF-effect .}, } @article {pmid39382326, year = {2024}, author = {Shafiq, M and Matamoros-Angles, A and Meister, SC and Glatzel, M}, title = {Comment on "Extracellular Vesicles Slow Down Aβ(1-42) Aggregation by Interfering with the Amyloid Fibril Elongation Step".}, journal = {ACS chemical neuroscience}, volume = {15}, number = {21}, pages = {3791-3793}, pmid = {39382326}, issn = {1948-7193}, mesh = {*Amyloid beta-Peptides/metabolism ; *Extracellular Vesicles/metabolism ; Humans ; *Peptide Fragments/metabolism ; Alzheimer Disease/metabolism/pathology ; Amyloid/metabolism ; Protein Aggregation, Pathological/metabolism ; Animals ; }, abstract = {Halipi et al. explored the impact of extracellular vesicles (EVs) on amyloid-β (Aβ) aggregation. They concluded that EVs reduce Aβ aggregation, as seen by shorter and thicker fibrils. While we agree with the complex role of EVs in Alzheimer's disease, we are sceptical of the claim that EVs slow down Aβ aggregation, noting missing key references. Previous literature rather suggests that EVs (derived from neuronal cell lines) accelerate the process of Aβ fibrillation and plaque formation. Halipi et al.'s findings may be skewed due to the lack of essential neuronally expressed Aβ-binding partners, like the prion protein (PrP[C]) in their EV samples. The commentary, in the light of included original experiments and cited literature, suggests that membrane proteins like PrP[C] are crucial to fully understand the role of EVs in Aβ aggregation, and Halipi et al.'s conclusions should be reexamined in light of these factors.}, } @article {pmid39381815, year = {2024}, author = {Vaismoradi, M and Rae, J and Turunen, H and Logan, PA}, title = {Specialized nurses' role in ensuring patient safety within the context of telehealth in home care: A scoping review.}, journal = {Digital health}, volume = {10}, number = {}, pages = {20552076241287272}, pmid = {39381815}, issn = {2055-2076}, abstract = {OBJECTIVES: Specialized nurses are uniquely positioned to implement innovative telehealth solutions to improve the quality and safety of home care, and this has become a focal point of contemporary healthcare research. This review aimed to identify the nature and scope of specialized nurses' roles in ensuring patient safety within the context of telehealth in home care.

METHODS: A scoping review of the international literature was carried out from January 1, 2013, to August 29, 2024. The review employed Levac et al.'s framework to delineate the research phenomenon and consolidate existing empirical research findings. Through a comparative analysis, the review integrated findings from selected studies, highlighting both similarities and differences related to this phenomenon, which led to the development of distinct categories.

RESULTS: The search yielded 1127 articles, from which 23 studies met the inclusion criteria for research synthesis and subsequent reporting of results. These studies spanned specialized nurses' roles in telehealth and various fields in which specialized nurses utilized telehealth to deliver high-quality and safe home care. The findings highlighted key outcomes linked to the improvement of patient safety in home care encompassing continuity of care, confidence in care, monitoring and early intervention, medication safety, engagement and adherence, and healthcare costs.

CONCLUSIONS: The review revealed the crucial role played by specialized nurses in harnessing telehealth in healthcare to meet the highest care standards, creating an environment that prioritizes the well-being and patient safety in home care.}, } @article {pmid39381597, year = {2024}, author = {Parkinson, LV and Geueke, B and Muncke, J}, title = {Potential mammary carcinogens used in food contact articles: implications for policy, enforcement, and prevention.}, journal = {Frontiers in toxicology}, volume = {6}, number = {}, pages = {1440331}, pmid = {39381597}, issn = {2673-3080}, abstract = {Many nations have food contact material (FCM) legislation purporting to protect citizens from hazardous chemicals, often specifically by regulating genotoxic carcinogens. Despite such regulations, cancers that are associated with harmful chemical exposures are highly prevalent, especially breast cancer. Using the novel Key Characteristics of Toxicants framework, Kay et al. found 921 substances that are potential mammary carcinogens. By comparing Kay et al.'s chemicals list with our own Database on migrating and extractable food contact chemicals (FCCmigex), we found that 189 (21%) of the potential mammary carcinogens have been measured in FCMs. When limiting these results to migration studies published in 2020-2022, 76 potential mammary carcinogens have been detected to migrate from FCMs sold in markets across the globe, under realistic conditions of use. This implies that chronic exposure of the entire population to potential mammary carcinogens from FCMs is the norm and highlights an important, but currently underappreciated opportunity for prevention. Reducing population-wide exposure to potential mammary carcinogens can be achieved by science-based policy amendments addressing the assessment and management of food contact chemicals.}, } @article {pmid39377829, year = {2024}, author = {Haque, ZA and Shaheen, S}, title = {"Enhancing post-craniotomy recovery: leveraging AI and network analysis for improved outcomes".}, journal = {Neurosurgical review}, volume = {47}, number = {1}, pages = {753}, doi = {10.1007/s10143-024-03020-9}, pmid = {39377829}, issn = {1437-2320}, mesh = {Humans ; *Craniotomy/methods ; *Artificial Intelligence ; *Brain Neoplasms/surgery ; Machine Learning ; Quality of Life ; Postoperative Complications ; }, abstract = {This letter addresses the importance of enhancing post-craniotomy care for primary brain tumor patients by leveraging insights from Rongqing Li et al.'s study on symptom networks. The study identified key central and bridge symptoms, such as sadness and difficulty understanding, which influence post-surgical recovery and quality of life. It also highlighted that patients with noninvasive tumors showed more cohesive symptom networks compared to those with invasive tumors. However, the study had limitations, including a short observation period and reliance on self-reported data, which restricted the depth of the findings.To optimize recovery, integrating artificial intelligence (AI) and machine learning (ML) could revolutionize post-craniotomy care. AI can assist with surgical planning, predict complications, and monitor recovery through wearable devices and real-time alerts. Natural Language Processing (NLP) can improve symptom detection from electronic health records, enhancing clinical decision-making. Despite the potential of these technologies, ethical concerns regarding data privacy and AI-generated report accuracy must be addressed. Future research should focus on long-term outcomes and refining AI applications to improve post-craniotomy symptom management and overall patient outcomes.}, } @article {pmid39375656, year = {2024}, author = {Wickramasinghe, S and Fisher, J and Taft, A and Makleff, S}, title = {Experiences of abortion care in Australia: a qualitative study examining multiple dimensions of access.}, journal = {BMC pregnancy and childbirth}, volume = {24}, number = {1}, pages = {652}, pmid = {39375656}, issn = {1471-2393}, mesh = {Humans ; Female ; *Health Services Accessibility ; *Qualitative Research ; Adult ; Australia ; *Abortion, Induced/psychology ; Pregnancy ; *COVID-19/epidemiology ; Young Adult ; Social Stigma ; SARS-CoV-2 ; }, abstract = {BACKGROUND: The United Nations' Sustainable Development Goals identify universal access to sexual and reproductive health services as a global priority. Yet barriers to abortion access remain, including legal restrictions, cost, stigma, and limited services and information. The aim was to identify barriers to and facilitators of abortion care access experienced in Australia.

METHODS: This qualitative phenomenological study examined abortion access in Australia, where abortion is decriminalised, from March 2020 to December 2022. We used social media and flyers in clinics to recruit adults who had sought abortion care, then interviewed them in-depth. We mapped participant experiences to five dimensions of access identified by Levesque et al.'s patient-centred access to healthcare framework: approachability, acceptability, availability and accommodation, affordability, and appropriateness.

RESULTS: The 24 participants lived across Australia and sought abortion during the COVID-19 pandemic. Approachability: Before seeking abortion, most did not know where to access information about the service and where to obtain it. Acceptability: Many were uncomfortable disclosing their abortion to family or friends; they reported that healthcare providers demonstrated varying levels of support. Availability and accommodation: Regional participants travelled far and faced long wait-times, exacerbated by pandemic restrictions. Affordability: Participants described financial stress paying for the service, travel, and related expenses. Appropriateness: Most participants expected judgemental care. Experiences varied widely: many participants experienced unempathetic, rushed, or judgemental interactions with healthcare staff, and many also reported at least one non-judgmental and supportive interaction on the same pathway to care.

DISCUSSION: Abortion seekers experienced varying obstacles when seeking care. The findings illustrate the need for population- and system-level initiatives such as: providing accurate information about and normalising abortion; implementing system-level strategies to reduce wait times, travel, and costs, especially for rural populations; and developing regulatory and quality improvement initiatives to increase the workforce and its readiness to provide high-quality, non-judgemental abortion care. Challenges seeking care during pandemic restrictions illustrate the importance of social support during care and choice between abortion modalities and service types. Consumer voices can help understand the diverse pathways to abortion care and inform solutions to overcome the multidimensional barriers to access.}, } @article {pmid39374999, year = {2024}, author = {Barry Hultquist, T and Kupzyk, K and LaFramboise, L and Leeseberg Stamler, L}, title = {Refinement and Evaluation of the Critical Thinking Self-Assessment Scale.}, journal = {Journal of nursing measurement}, volume = {}, number = {}, pages = {}, doi = {10.1891/JNM-2024-0061}, pmid = {39374999}, issn = {1945-7049}, abstract = {Background and Purpose: Critical thinking (CT) skills are necessary tools for enhancing patient care. The Critical Thinking Self-Assessment Scale (CTSAS) was based on Facione et al.'s (1990) schema of 6 CT skills and 16 subskills. Although early results indicated a strong instrument, it was lengthy at 115 items. The study purpose was to statistically reduce the number of items in the instrument. Methods: Using a sample of 712 undergraduate nursing students, item analysis and confirmatory factor analysis were used to determine items to retain and delete. The scale was validated by comparing to the Need for Cognition Scale. Results: Items were reduced to 46 and spread over the 16 subskills. Conclusions: The revised CTSAS is a valid, reliable tool that is greatly reduced in length without compromising its psychometric properties. Faculty could use the measure as a reflection of students' levels on these skills and design learning activities to target problem areas.}, } @article {pmid39366522, year = {2024}, author = {Taylor, N and Boyland, E and Hardman, CA}, title = {Conceptualising food banking in the UK from drivers of use to impacts on health and wellbeing: A systematic review and directed content analysis.}, journal = {Appetite}, volume = {203}, number = {}, pages = {107699}, doi = {10.1016/j.appet.2024.107699}, pmid = {39366522}, issn = {1095-8304}, mesh = {Humans ; United Kingdom ; *Food Insecurity ; Food Assistance ; Female ; Male ; Food Supply ; }, abstract = {Food banks have become commonplace in the UK as an emergency response to food insecurity. However, food banks are not a long-term solution to food insecurity and are often not accessed by those in need. In the context of the cost-of-living crisis, and increased food insecurity, this systematic review applied market/government failure theory, voluntary failure theory, and Radimer et al.'s (1990) domains of food insecurity to explore three important aspects relevant to the food banking experience: the drivers of food bank use; the limitations of the current food bank model; and the impacts of the food banking model for food bank clients. Empirical, peer-reviewed articles written in English with a UK food bank context and reporting relevant data to these aspects were eligible for inclusion. In total, 221 titles were identified using four databases (Web of Science, SCOPUS, PubMed, CINHAL Plus) in July 2022. The final sample of 41 articles (comprising qualitative, quantitative and mixed methods studies), were quality assessed using the Mixed Methods Appraisal Tool. Data were extracted and analysed through directed content analysis. Market and government failures were widely reported to drive food bank use. Insufficiency, paternalism and particularism represented key limitations of the food bank model. Negative health and psychological impacts of food bank use were prominent, yet social impacts were largely positive. Consequently, new solutions are needed to promote positive health and psychological impacts for food bank clients in the UK. The application of these findings to other high-income countries experiencing food insecurity should be determined.}, } @article {pmid39361407, year = {2024}, author = {Kim, SY and Neblett, EW and Ross, RJ and Millan, F and Hsu, HH}, title = {Apology for the publication of Sheng et al. (2024).}, journal = {Cultural diversity & ethnic minority psychology}, volume = {30}, number = {4}, pages = {599-602}, doi = {10.1037/cdp0000708}, pmid = {39361407}, issn = {1099-9809}, mesh = {Child ; Humans ; Cultural Diversity ; *Empathy ; Ethnicity/psychology ; *Racism/psychology ; Tibet/ethnology ; }, abstract = {Recently, Cultural Diversity & Ethnic Minority Psychology (CDEMP) published Sheng et al.'s (see record 2024-72017-001) article titled "The Development of Tibetan Children's Racial Bias in Empathy: The Mediating Role of Ethnic Identity and Wrongfulness of Ethnic Intergroup Bias." The article went through the standard peer review process. Subsequent to its publication, one of our readers expressed concerns regarding the biased language (e.g., "backwardness of education") and deficit-oriented interpretation of findings (e.g., "the geographical environment and traditional way of life in Tibet can also impact the development of [racial biases in empathy] in Tibetan children"). The reader rightly pointed out that this language and interpretation reinforce imperialism, particularly given the complex relations between Tibet and China. We sincerely apologize to our readers, and especially to our Tibetan colleagues, for failing to identify these issues prior to the publication of the article.Wetake accountability for the oversight and have followed due process to correct our mistakes in the publication of this article. We will also take action to prevent this from happening again. In this editorial, we describe the study, actions taken by the CDEMP Editorial Team, the authors' response, and future actions to be taken by the CDEMP Editorial Team. (PsycInfo Database Record (c) 2024 APA, all rights reserved).}, } @article {pmid39358759, year = {2024}, author = {Nilsson, I and Busck-Rasmussen, M and Villadsen, SF}, title = {Development of a complex intervention to strengthen municipality-based breastfeeding support to reduced social inequity in breastfeeding.}, journal = {Archives of public health = Archives belges de sante publique}, volume = {82}, number = {1}, pages = {174}, pmid = {39358759}, issn = {0778-7367}, abstract = {BACKGROUND: Breastfeeding is the ideal nutrition for infants and protects infants and mothers from a range of adverse health outcomes during their lifespan. In Denmark, while the breastfeeding initiation rate is high, only 14% of mothers meet the World Health Organization's recommendation of exclusive breastfeeding at six months. Furthermore, a notable social inequity exists among those who achieve this recommendation. Knowledge of effective interventions to reduce breastfeeding inequity is limited. A previous hospital-based intervention succeeded in increasing breastfeeding duration. However, most breastfeeding support is provided in Danish municipalities by health visitors. This called for adapting the intervention to the health visiting program and developing an intensified intervention addressing the social inequity in breastfeeding. This article describes the adaptation and development process of a municipality-based intervention.

METHODS: During a 15-month period in 2020-21, the municipal intervention was iteratively developed using a three-stage framework for developing complex health interventions described by Hawkins et al. The three stages were 1) need assessment and stakeholder consultation, 2) co-production and 3) prototyping. The process was inspired by O'Cathain et al.'s principles for a user-centred, co-created and theory- and evidence-based approach, involving parents and health visitors.

RESULTS: In stage 1, we identified the needs and priorities of the target groups of the intervention. In stage 2, the intervention was developed through action research design and inspired by Duus' 'learning cycles' as the method to enhance motivation and ownership and to strengthen the implementation process by creating a joint room for learning and reflection with health visitors and developers. In stage 3, the intervention was tested for feasibility and usefulness during a 2.5-month period accompanied by monthly dialogue meetings with health visitors and developers. In this period, the intervention was refined based on the gathered experiences and was subsequently prepared for evaluation.

CONCLUSION: The description of the development of this complex intervention, aimed at increasing breastfeeding duration and reducing inequity, offers breastfeeding practitioners and researchers a transparent foundation for continuously improving breastfeeding support and a methodology for complex intervention development.

TRIAL REGISTRATION: Registered at Clinical Trials NCT05311631.}, } @article {pmid39353224, year = {2024}, author = {Johnson, B and Shakes, P and Maylea, C}, title = {Prenatal testing technologies in Australia: Unintended clinical and emotional complexities in underprepared systems.}, journal = {Social science & medicine (1982)}, volume = {361}, number = {}, pages = {117368}, doi = {10.1016/j.socscimed.2024.117368}, pmid = {39353224}, issn = {1873-5347}, mesh = {Humans ; Australia ; Female ; Pregnancy ; *Prenatal Diagnosis/methods/psychology ; Health Personnel/psychology ; Surveys and Questionnaires ; Emotions ; }, abstract = {The past decade has seen technological advances in prenatal screening technologies rapidly integrated into clinical practice. These technologies have revolutionised healthcare and raised complex socio-ethical issues such as equitable access, medical commercialisation, and new eugenics. However, the important issue of the impact of these technologies on healthcare professionals is receiving less attention. Exploring this issue in the Australian context, we conducted a survey from August to November 2022, targeting health and allied health professionals who work with parents in the perinatal period who have received a fetal diagnosis. We received 75 substantive responses from a diversity of professionals, including sonographers, midwives, genetic counsellors and medical providers. In this article, we consider the unintended impacts of prenatal screening technologies on healthcare workers, drawing from Ziebland et al., 's 2021 unintended consequences framework. Our reflexive thematic analysis produced three key themes: "Unintended Clinical Complexities", "Adapting Work Practices to Keep Up in Systems that Lack", and "Unintended Intensification of Emotional Labour". Prenatal testing technologies have intentionally increased early testing and fetal information, offering veiled promises of increased certainty in pregnancy. However, our analysis highlights that these advancing technologies also generate more ambiguous results, creating unintended clinical and emotional complexities for healthcare providers. Workers must manage increased clinical uncertainty and constant change, creating intensified emotional labour in under-prepared systems. We conclude by identifying the need to recognise the impacts of advancing prenatal screening technologies on healthcare workers and for targeted professional training to prepare healthcare professionals for the complexities introduced by these new technologies.}, } @article {pmid39353040, year = {2024}, author = {Cifuentes-González, C and Bocanegra-Oyola, N and de-la-Torre, A}, title = {Authors Reply to Letter to the Editor - In Response to: Comment on Bocanegra-Oyola et al.'s "Clinical Characteristics of Ocular Mucous Membrane Pemphigoid: A Systematic Review and Meta-Analysis".}, journal = {Ocular immunology and inflammation}, volume = {32}, number = {10}, pages = {2624-2625}, doi = {10.1080/09273948.2024.2408649}, pmid = {39353040}, issn = {1744-5078}, mesh = {Humans ; *Pemphigoid, Benign Mucous Membrane/diagnosis ; Biopsy ; Diagnosis, Differential ; }, abstract = {In response to Dr. Kasperkiewicz's commentary on our meta-analysis conducted by Bocanegra-Oyola et al., we fully agree with refining diagnostic processes for ocular pemphigoid, particularly in differentiating it from pseudopemphigoid. We concur that relying solely on clinical findings may result in misdiagnoses. Confirming the diagnosis via biopsy can be challenging, requiring multiple biopsies in some patients, and should always be supported by a multidisciplinary clinical assessment involving ophthalmologists and dermatologists.}, } @article {pmid39356431, year = {2024}, author = {Shin, J and Gibson, JS and Jones, RA and Debnam, KJ}, title = {Factors associated with anxiety in colorectal cancer survivors: a scoping review.}, journal = {Journal of cancer survivorship : research and practice}, volume = {}, number = {}, pages = {}, pmid = {39356431}, issn = {1932-2267}, abstract = {PURPOSE: Anxiety is one of the most common psychological issues among colorectal cancer (CRC) survivors. It can interact with physical symptoms, impacting cancer progression, survival, and quality of life. This scoping review aims to explore the factors associated with anxiety in patients with CRC and the instruments used to measure anxiety.

METHODS: Using Arksey and O'Malley's (2005) framework for the scoping review, studies investigating anxiety in CRC patients published in CINAHL, PubMed, PsycINFO, and Scopus between 2013 and 2024 were included.

RESULTS: We analyzed fifty-one studies for this review. The review identified several risk factors and consequences of anxiety in CRC patients. The risk factors were classified into six domains using Niedzwiedz et al.'s (2019) framework: individual characteristics, social/ contextual factors, prior psychological factors, psychological responses to diagnosis and treatment, characteristics of cancer, and treatment. The consequences of anxiety were classified into three categories: global health status/quality of life, functions, and symptoms/problems. The most frequently used tool was the Hospital Anxiety and Depression Scale, with International Classification of Diseases codes being the second most used.

CONCLUSIONS: This scoping review highlighted the intricate interaction between biological and psychosocial aspects in the lives of CRC survivors. It also identified unique factors associated with anxiety among these individuals. However, the review found some inconsistencies in the results related to anxiety-related factors, potentially due to differences in study populations, designs, measurement tools, and analysis methods.

This review underscores the potential for interventions targeting modifiable factors to prevent or reduce anxiety and enhance the quality of life for CRC survivors.}, } @article {pmid39356236, year = {2024}, author = {Quadrelli, M and Baccaglini, T and Morra, A}, title = {Quadrelli et al.'s comments on Cohort studies using 3D-CT are needed to assess whether "home Gym-Bed" exercises are beneficial against sarcopenia.}, journal = {European journal of translational myology}, volume = {34}, number = {3}, pages = {}, doi = {10.4081/ejtm.2024.13135}, pmid = {39356236}, issn = {2037-7452}, abstract = {We appreciate the thorough and insightful comments provided by Josef Finsterer regarding our study on the prevention of sarcopenia using the "Gym Bed" exercise regimen. We welcome the opportunity to address the points raised and to elaborate on the implications and limitations of our research.[...].}, } @article {pmid39344387, year = {2024}, author = {Cao, S and Su, H and Zhang, X and Fang, C and Wu, N and Zeng, Y and Chen, M}, title = {Mendelian Randomization Study Supports Genetic Liability to Obsessive-Compulsive Disorder Associated With the Risk of Alzheimer's Disease.}, journal = {Brain and behavior}, volume = {14}, number = {10}, pages = {e70081}, pmid = {39344387}, issn = {2162-3279}, support = {2022JJ70149//Natural Science Foundation of Hunan Province/ ; }, mesh = {Humans ; *Alzheimer Disease/genetics ; *Obsessive-Compulsive Disorder/genetics/epidemiology ; *Mendelian Randomization Analysis ; *Genome-Wide Association Study ; *Genetic Predisposition to Disease ; Risk Factors ; Polymorphism, Single Nucleotide ; }, abstract = {BACKGROUND: Observational studies have suggested that obsessive-compulsive disorder (OCD) may be associated with Alzheimer's disease (AD). However, whether OCD is a causal risk factor for AD remains unclear. This study aimed to assess the causal effect of OCD on AD risk by performing a two-sample Mendelian randomization (MR) analysis.

METHODS: Genome-wide association summary statistics were obtained for OCD, comprising 2688 cases and 7037 controls, as well as for AD, including 21,982 cases and 41,944 controls from Kunkle et al.'s study, and 39,918 cases and 358,140 controls from Wightman et al.'s study. On the basis of two diverse thresholds, OCD-associated genetic variants were screened as instrumental variables (IVs) for subsequent MR analyses. Inverse variance weighed was the primary MR method. MR-Egger, weighted median, and weighted mode were used as supplementary MR methods. Various sensitivity tests assessed the reliability of MR results.

RESULTS: On the basis of strict IV selecting thresholds, inverse-variance weighted (IVW) identified significant causal associations between genetic liability to OCD and increased risk of AD in two different sources ((i) Kunkle et al.: odds ratio [OR] = 1.070, 95% confidence interval [CI]: 1.015-1.127, p = 0.012; (ii) Wightman et al. 0.012; (iii) Wightman et al.: OR = 1.051, 95% CI: 1.014-1.090, p = 0.007). Three other supplementary MR methods yielded similar results to IVWs (OR > 1). Furthermore, all results were replicated in MR analyses based on lenient IV selecting thresholds. The sensitivity tests indicated that MR results were stable and not affected by significant horizontal pleiotropy.

CONCLUSIONS: This comprehensive MR study suggests that genetic liability to OCD is a causal risk factor for AD. Early intervention in patients with OCD may be beneficial in preventing future AD progression.}, } @article {pmid39329232, year = {2024}, author = {Campbell, H and Gustafson, P}, title = {Discussion on "LEAP: the latent exchangeability prior for borrowing information from historical data" by Ethan M. Alt, Xiuya Chang, Xun Jiang, Qing Liu, May Mo, H. Amy Xia, and Joseph G. Ibrahim.}, journal = {Biometrics}, volume = {80}, number = {3}, pages = {}, doi = {10.1093/biomtc/ujae084}, pmid = {39329232}, issn = {1541-0420}, support = {RGPIN-2019-03957//NSERC/ ; }, mesh = {Humans ; *Models, Statistical ; Biometry/methods ; Data Interpretation, Statistical ; }, abstract = {We commend Alt et al.'s innovative approach for analysis with a hybrid control arm while offering insights into two key considerations: the necessity for extrapolation and the potential benefits of curating historical control data before analysis.}, } @article {pmid39328851, year = {2024}, author = {Gorgy, A and Al Hashemi, R and Efanov, JI}, title = {Insights into upper blepharoplasty: Conservative volume-preserving techniques.}, journal = {World journal of clinical cases}, volume = {12}, number = {27}, pages = {6129-6131}, pmid = {39328851}, issn = {2307-8960}, abstract = {This editorial commentary critically examines the systematic review by Miotti et al, which discusses the evolving trends in upper lid blepharoplasty towards a conservative, volume-preserving approach. The review emphasizes the shift from traditional tissue resection to techniques that maintain anatomical integrity, paralleling broader trends in panfacial rejuvenation. Miotti et al delve into the nuances of fat pad management, advocating for conservation over reduction to sustain natural contours and improve long-term aesthetic outcomes. This perspective is supported by comparative studies and empirical data, such as those from Massry and Alghoul et al, highlighting the benefits of conservative approaches in terms of patient satisfaction and aesthetic longevity. The review also stresses the importance of surgeon discretion in adapting procedures to diverse patient demographics, particularly in addressing distinct features such as the Asian upper eyelid. However, it identifies a significant gap in long-term comparative research, underscoring the need for future studies to substantiate the safety and efficacy of these minimalist techniques. Overall, Miotti et al.'s work contributes profoundly to the discourse on personalized, conservative cosmetic surgery, urging ongoing research to refine and validate surgical best practices in upper eyelid blepharoplasty.}, } @article {pmid39328732, year = {2024}, author = {Topkan, E and Somay, E and Besen, AA and Mertsoylu, H}, title = {Comment on: Does the Planning Target Volume Correlate with Toxicity for Head and Neck Cancer Patients Undergoing Radiation? A Prospective Observational Study.}, journal = {Indian journal of surgical oncology}, volume = {15}, number = {Suppl 3}, pages = {481-482}, pmid = {39328732}, issn = {0975-7651}, abstract = {We highly praised Ujjayani et al.'s [1] report on the effect of target volume planning (PTV) on toxicities in 35 patients with head and neck cancer (HNC) who underwent intensity-modulated radiation therapy (IMRT) with/without chemotherapy. Although the results of the current study are quite valuable and inspiring, we have two suggestions.}, } @article {pmid39325718, year = {2024}, author = {Salvioli, M and Vandelaer, L and Baena, E and Schneider, K and Cavill, R and Staňková, K}, title = {The effect of tumor composition on the success of adaptive therapy: The case of metastatic Castrate-Resistant Prostate Cancer.}, journal = {PloS one}, volume = {19}, number = {9}, pages = {e0308173}, pmid = {39325718}, issn = {1932-6203}, mesh = {Male ; Humans ; *Prostate-Specific Antigen/metabolism ; *Prostatic Neoplasms, Castration-Resistant/pathology/metabolism/drug therapy ; *Testosterone/blood ; Neoplasm Metastasis ; Disease Progression ; }, abstract = {Prostate-specific antigen (PSA) is the most commonly used serum marker for prostate cancer. It plays a role in cancer detection, treatment monitoring, and more recently, in guiding adaptive therapy protocols, where treatment is alternated based on PSA levels. However, the relationship between PSA levels and tumor volume remains poorly understood. Empirical evidence suggests that different cancer cell types produce varying amounts of PSA. Despite this, current mathematical cancer models often assume either that all cell types contribute equally to PSA levels or that only certain subpopulations produce PSA at fixed rates. In this study, we compare Zhang et al.'s classical adaptive therapy protocol with the standard of care, which involves continuous maximum tolerable dose treatment, under different assumptions regarding PSA production. Specifically, we explore the possibility that testosterone-dependent, testosterone-producing, and testosterone-independent cells contribute to PSA production to varying degrees. We use the time to competitive release as a proxy for the time to disease progression. Our findings indicate that adaptive therapy consistently results in a longer time to competitive release compared to the standard of care, regardless of the assumptions about PSA production. However, when testosterone-independent cells are the sole PSA producers, Zhang et al.'s adaptive therapy protocol becomes inapplicable, as PSA levels never fall to half of their initial value, preventing therapy discontinuation. Additionally, we observe that the number and duration of treatment cycles in adaptive therapy are highly sensitive to assumptions about how much each cell type contributes to PSA production. Overall, our results emphasize the need for a deeper understanding of patient-specific PSA dynamics, which could enhance the effectiveness of adaptive therapy in prostate cancer treatment.}, } @article {pmid39325387, year = {2024}, author = {Abramson, L and Pener-Tessler, R and Kleper, D and Saudino, KJ and Gagne, JR and Angel, M and Knafo-Noam, A}, title = {The structure, development, and etiology of observed temperament during middle childhood.}, journal = {Developmental psychology}, volume = {60}, number = {11}, pages = {2084-2100}, doi = {10.1037/dev0001818}, pmid = {39325387}, issn = {1939-0599}, support = {//European Research Council; H2020/ ; }, mesh = {Humans ; *Temperament/physiology ; Male ; Female ; Child ; *Child Development/physiology ; Child Behavior/physiology ; Israel ; Longitudinal Studies ; Factor Analysis, Statistical ; }, abstract = {Investigating the structure and etiology of temperament is key to understanding how children interact with the world (Kagan, 1994). Although these topics have yielded an abundance of research, fewer studies have employed observational data during middle childhood, when unique environmental challenges could influence temperament development. To address this gap, Israeli twin children were observed at Age 6.5 (N = 1,083, 564 families; 50.6% females) and again at Age 8-9 (N = 768, 388 families; 52.0% females; 611 children from 322 families had data from both ages). Temperament was assessed globally by trained coders and, at Age 8-9, also by the experimenter who interacted with the child. We examined whether Rothbart et al.'s (2000) three-factor model, according to which temperament includes the domains negative affect, positive affect/surgency, and effortful control, emerges from the data. In addition, we considered a bifactor model, where a fourth global factor accounts for all behaviors' commonality. Across the two ages and rating methods, confirmatory factor analyses supported the bifactor model. The global factor's loadings suggested that it reflects children's expressiveness. Adding this factor changed the associations between the other factors and enabled differentiation between surgency and positive affect. This suggests that in observational settings that capture temperament impressions holistically, children's expressiveness affects other traits' behavioral displays. Twin models revealed genetic influences for most traits. Importantly, twin models revealed shared-environmental influences for negative affect and expressiveness, which modestly contributed to temperament consistency across ages. These findings shed light on temperament traits' interrelatedness and stress the importance of the shared environment to temperament development during middle childhood. (PsycInfo Database Record (c) 2024 APA, all rights reserved).}, } @article {pmid39324557, year = {2024}, author = {Maccarone, MC and Caregnato, A and Regazzo, G and Carriero, A and Casellato, G and Finamoni, C and Jirillo, R and Laskova, O and Marigo, E and Sánchez, DY and Seno, I and Venturin, C and Veronese, H and Ravara, B and Giurati, W and Carraro, U and Masiero, S}, title = {Maccarone et al.'s comments on Cohort studies using 3D-CT are needed to assess whether "home Gym-Bed" exercises are beneficial against sarcopenia.}, journal = {European journal of translational myology}, volume = {34}, number = {3}, pages = {}, pmid = {39324557}, issn = {2037-7452}, abstract = {We appreciate the insightful comments provided by Josef Finsterer regarding our article on the first evidence on the effects of the Home Full-Body in-Bed Gym protocol as a potential intervention to mitigate age-related muscle loss based on the preliminary positive results of a Padua prospective observational study.1 We acknowledge the importance of the points raised and would like to address them in this response. At the University of Padua, we conducted a study aimed at evaluating the impact of a home-based Full-Body in-Bed Gym protocol on various outcomes in elderly individuals, which was published in 2023.1 The rational of our proposal is based on the fact that functional muscle decay of aging is inevitable, but that the general population is highly hypoactive, let's say "lazy". The increase in daily muscular activity even through "Home In-Bed Gym" recovers at least in part the potential abilities progressively lost. Therefore, it is easy to rejuvenate the "lazy" population, that is, the vast majority of elderlies.[...].}, } @article {pmid39324295, year = {2024}, author = {Shaw, J and Nizzer, S and McKay, S}, title = {Technology, Aging and Home and Community Care: Picking the Right Problems to Solve.}, journal = {HealthcarePapers}, volume = {22}, number = {2}, pages = {25-30}, doi = {10.12927/hcpap.2024.27400}, pmid = {39324295}, issn = {1929-6339}, mesh = {Humans ; Canada ; *Home Care Services ; *Aging ; Community Health Services/organization & administration ; Digital Technology ; Aged ; }, abstract = {As the Canadian population ages, the imperative to support aging in the community grows increasingly urgent. In this commentary, we build on Kokorelias et al.'s (2024) article to address the ethically appropriate role of digital technologies in supporting aging at home. We argue that a nuanced perspective on this topic is crucial. Focusing on the pivotal role of personal support workers in home and community care, we highlight the multiple challenges they face, from precarious employment to safety concerns. While digital innovations offer promise, we suggest that a holistic approach blending policy initiatives with technological advancements is imperative.}, } @article {pmid39315426, year = {2024}, author = {Hussain, NA}, title = {Heteronormativity in Canadian Healthcare: Revisioning a Queer-Focused Realm.}, journal = {HealthcarePapers}, volume = {22}, number = {1}, pages = {63-68}, doi = {10.12927/hcpap.2024.27384}, pmid = {39315426}, issn = {1929-6339}, mesh = {Humans ; Canada ; *Sexual and Gender Minorities ; *Delivery of Health Care ; Health Policy ; Health Equity ; }, abstract = {Kia et al.'s (2024) article, "Beyond the Rainbow: Advancing 2S/LGBTQ+ Health Equity at a Time of Political Volatility," illustrates the health discrepancies that the Two-Spirit, lesbian, gay, bisexual, transgender, queer, intersex, asexual and other sexual and gender minority (2SLGBTQIA+) community withstand and the Canadian healthcare system's legacy of heteronormativity. This commentary focuses on the straight-centred approach of the Canadian medical system that neglects, harms and fails the 2SLGBTQIA+ population, resulting in a decline in their mental and physical well-being and increased rates of morbidity for queer individuals. The 2SLGBTQIA+ community must be placed in the front and centre of integral decision making and have the final word in policy changes within Canadian regulatory bodies.}, } @article {pmid39311518, year = {2024}, author = {Stussi, Y and Dukes, D and Sander, D}, title = {The added value of affective processes for models of human cognition and learning.}, journal = {The Behavioral and brain sciences}, volume = {47}, number = {}, pages = {e165}, doi = {10.1017/S0140525X24000207}, pmid = {39311518}, issn = {1469-1825}, mesh = {Humans ; *Cognition/physiology ; *Learning/physiology ; *Affect/physiology ; Social Learning/physiology ; Models, Psychological ; Reinforcement, Psychology ; Emotions/physiology ; }, abstract = {Building on the affectivism approach, we expand on Binz et al.'s meta-learning research program by highlighting that emotion and other affective phenomena should be key to the modeling of human learning. We illustrate the added value of affective processes for models of learning across multiple domains with a focus on reinforcement learning, knowledge acquisition, and social learning.}, } @article {pmid39311515, year = {2024}, author = {Calderan, M and Visalli, A}, title = {Challenges of meta-learning and rational analysis in large worlds.}, journal = {The Behavioral and brain sciences}, volume = {47}, number = {}, pages = {e148}, doi = {10.1017/S0140525X24000128}, pmid = {39311515}, issn = {1469-1825}, mesh = {Humans ; *Bayes Theorem ; Learning ; Cognition/physiology ; }, abstract = {We challenge Binz et al.'s claim of meta-learned model superiority over Bayesian inference for large world problems. While comparing Bayesian priors to model-training decisions, we question meta-learning feature exclusivity. We assert no special justification for rational Bayesian solutions to large world problems, advocating exploring diverse theoretical frameworks beyond rational analysis of cognition for research advancement.}, } @article {pmid39308380, year = {2024}, author = {Laham, KB and Duea, SR and Sigmon, LB and Santibanez-Mendez, A and Koernig, HL}, title = {Partnership to Increase Care Access Through Mobile Outreach to Migrant Farm Communities: A Feasibility Study.}, journal = {Progress in community health partnerships : research, education, and action}, volume = {18}, number = {3}, pages = {363-370}, pmid = {39308380}, issn = {1557-055X}, mesh = {Humans ; *Transients and Migrants ; *Feasibility Studies ; *Health Services Accessibility/organization & administration ; *Community-Institutional Relations ; *Farmers ; Mobile Health Units/organization & administration ; Community-Based Participatory Research/organization & administration ; }, abstract = {BACKGROUND: Health care access for migrant farmworkers is limited given the nature of seasonal farm work, including migration patterns, capacity, and availability of local community health services. Consideration of these contextual elements when exploring a community-academic partnership to increase access to care for migrant farmworkers is essential.

OBJECTIVE: Explore the partnerships and processes for integrating nursing faculty and students from a regional public university's school of nursing into a farmworker health outreach program's mobile clinic process.

METHODS: A feasibility study was undertaken using Bowen et al.'s feasibility framework.

RESULTS: Integrating faculty and students into the farmworker health outreach program's mobile clinic process was determined to be feasible.

CONCLUSIONS: Integrating faculty providers and students into a farmworker outreach program's mobile health process has several nuances requiring consideration before operationalizing the partnership, including nursing faculty practice (e.g., credentialing, malpractice insurance), student clinical placement processes, the farmworker outreach program's processes, and farmworker availability.}, } @article {pmid39307154, year = {2024}, author = {Pal, S and Chataway, J and Swingler, R and Macleod, MR and Carragher, NO and Hardingham, G and Selvaraj, BT and Smith, C and Wong, C and Newton, J and Lyle, D and Stenson, A and Dakin, RS and Ihenacho, A and Colville, S and Mehta, AR and Stallard, N and Carpenter, JR and Parker, RA and Keerie, C and Weir, CJ and Virgo, B and Morris, S and Waters, N and Gray, B and MacDonald, D and MacDonald, E and Parmar, MKB and Chandran, S and , }, title = {Safety and efficacy of memantine and trazodone versus placebo for motor neuron disease (MND SMART): stage two interim analysis from the first cycle of a phase 3, multiarm, multistage, randomised, adaptive platform trial.}, journal = {The Lancet. Neurology}, volume = {23}, number = {11}, pages = {1097-1107}, doi = {10.1016/S1474-4422(24)00326-0}, pmid = {39307154}, issn = {1474-4465}, mesh = {Humans ; *Trazodone/therapeutic use/pharmacology ; Male ; Middle Aged ; Female ; Aged ; *Memantine/therapeutic use ; Double-Blind Method ; *Motor Neuron Disease/drug therapy ; Treatment Outcome ; Adult ; }, abstract = {BACKGROUND: Motor neuron disease represents a group of progressive and incurable diseases that are characterised by selective loss of motor neurons, resulting in an urgent need for rapid identification of effective disease-modifying therapies. The MND SMART trial aims to test the safety and efficacy of promising interventions efficiently and definitively against a single contemporaneous placebo control group. We now report results of the stage two interim analysis for memantine and trazodone.

METHODS: MND SMART is an investigator-led, phase 3, double-blind, placebo-controlled, multiarm, multistage, randomised, adaptive platform trial recruiting at 20 hospital centres in the UK. Individuals older than 18 years with a confirmed diagnosis of either amyotrophic lateral sclerosis classified by the revised El Escorial criteria, primary lateral sclerosis, progressive muscular atrophy, or progressive bulbar palsy, regardless of disease duration, were eligible for screening. Participants were randomised (1:1:1) to receive oral trazodone 200 mg once a day, oral memantine 20 mg once a day, or matched placebo using a computer-generated minimisation algorithm delivered via a secure web-based system. Co-primary outcome measures were clinical functioning, measured by rate of change in the Amyotrophic Lateral Sclerosis Functional Rating Scale Revised (ALSFRS-R), and survival. Comparisons were conducted in four stages, with predefined criteria for stopping at the end of stages one and two. We report interim analysis from the stage two results, which was done when 100 participants per group (excluding long survivors, defined as >8 years since diagnosis at baseline) completed a minimum of 12 months of follow-up for the candidate investigational medicinal products. The trial is registered on the European Clinical Trials Registry, 2019-000099-41, and ClinicalTrials.gov, NCT04302870, and is ongoing.

FINDINGS: Between Feb 27, 2020, and July 24, 2023 (database lock for interim analysis two), 554 people with a motor neuron disease were randomly allocated to memantine (183 [33%]), trazodone (185 [33%]), or placebo (186 [34%]). The primary interim analysis population comprised 530 participants, of whom 175 (33%) had been allocated memantine, 175 (33%) had been allocated trazodone, and 180 (34%) had been allocated placebo. Over 12 months of follow-up, the mean rate of change per month in ALSFRS-R was -0·650 for memantine, -0·625 for trazodone, and -0·655 for placebo (memantine versus placebo estimated mean difference 0·033, one-sided 90% CI lower level -0·085; one-sided p=0·36; trazodone vs placebo: 0·065, -0·051; one-sided p=0·24). The one-sided p values were both above the significance threshold of 10%, indicating that neither memantine nor trazodone groups met the criteria for continuation. There were 483 participants with at least one adverse event (145 [77%] on placebo, 170 [91%] on memantine, and 168 [90%] on trazodone). There were 88 participants with at least one serious adverse event (37 [20%] on memantine, 27 [14%] on trazodone, and 24 [13%] on placebo). A total of 11 serious adverse event led to treatment discontinuation. There was no survival difference between comparisons, with 49 deaths in the memantine group, 52 deaths in the trazodone group, and 48 deaths in the placebo group.

INTERPRETATION: Neither memantine nor trazodone improved efficacy outcomes compared with placebo. This result is sufficiently powered to warrant no further testing of trazodone or memantine in motor neuron disease at the doses evaluated in this study. The multiarm multistage design shows important benefits in reducing the time, cost, and participant numbers to reach a definitive result.

FUNDING: The Euan MacDonald Centre, MND Scotland, My Name'5 Doddie Foundation, and Baillie Gifford.}, } @article {pmid39306243, year = {2025}, author = {Tugcu, AO and Dogru, GD and Dursun, CU}, title = {Commentary on Bentsen et al.'s study of rib fracture risk after stereotactic body radiotherapy.}, journal = {Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology}, volume = {202}, number = {}, pages = {110536}, doi = {10.1016/j.radonc.2024.110536}, pmid = {39306243}, issn = {1879-0887}, } @article {pmid39298210, year = {2024}, author = {Fritzson, E and Salafia, C and Bellizzi, KM and Park, CL}, title = {Cascading pathways from physical symptom burden to distress in adults with cancer.}, journal = {Health psychology : official journal of the Division of Health Psychology, American Psychological Association}, volume = {}, number = {}, pages = {}, pmid = {39298210}, issn = {1930-7810}, support = {UH3 CA220642/CA/NCI NIH HHS/United States ; }, abstract = {OBJECTIVE: Psychological distress in cancer survivors may be partially attributable to fear of cancer recurrence (FCR). Simonelli et al. (2017) proposed a conceptual model of FCR, which suggests that cancer cues (e.g., physical symptoms) may prompt maladaptive emotional processing leading to heightened FCR, and thus increased psychological distress. This prospective study tested this model by examining the cascading pathways by which physical symptom burden, emotion dysregulation, and FCR were associated with posttraumatic stress symptoms (PTSS) and anxiety among recently diagnosed cancer survivors.

METHOD: Psychosocial and well-being data from 486 breast (63.7%), prostate (25.7%), and colorectal (10.7%) cancer survivors (Mage = 58.7 years; 31% male) were collected over 12 months as they transitioned off primary treatment into early survivorship. A path analysis was performed to examine whether physical symptom burden led to more emotion dysregulation and elevated FCR and, in turn, more psychological distress (PTSS and anxiety).

RESULTS: Greater physical symptom burden at Time 1 was associated with more emotion dysregulation at Time 2, which was related to heightened FCR at Time 3 and, in turn, more psychological distress at Time 4. Additionally, the indirect effect of physical symptom burden on FCR through emotion dysregulation and the indirect effects of emotion dysregulation on PTSS and anxiety through FCR were also significant.

CONCLUSIONS: The findings support Simonelli et al.'s (2017) conceptual model of FCR and distress and highlight the importance of assessing and addressing physical symptom burden and improving emotional processing abilities to help mitigate heightened psychological distress among cancer survivors. (PsycInfo Database Record (c) 2024 APA, all rights reserved).}, } @article {pmid39304878, year = {2024}, author = {Gozzi, P and Persson, M and Nielsen, A and Kilander, H and Kågesten, AE and Iwarsson, KE and Ljungcrantz, D and Bredell, M and Larsson, EC}, title = {Contraceptive access and use among women with migratory experience living in high-income countries: a scoping review.}, journal = {BMC public health}, volume = {24}, number = {1}, pages = {2569}, pmid = {39304878}, issn = {1471-2458}, mesh = {Humans ; Female ; *Health Services Accessibility ; *Developed Countries ; *Contraception Behavior/statistics & numerical data/psychology ; Transients and Migrants/psychology/statistics & numerical data ; Contraception/statistics & numerical data/psychology ; Europe ; North America ; Australasia ; }, abstract = {BACKGROUND: Women who have migrated often encounter difficulties in accessing healthcare and experience inequitable sexual and reproductive health outcomes in destination countries. These health inequities include contraceptive access and use. To better understand what influences contraceptive access and use, this scoping review set out to synthesize the evidence on contraceptive access and use and on associated interventions among women with migratory experience in high-income countries (HICs) in Europe, North America and Australasia.

METHODS: The scientific databases PubMed, Web of Science and CINAHL were searched for peer-reviewed quantitative, qualitative and mixed method articles published between January 2000 and June 2023. Articles were included if they reported on studies exploring contraceptive use to prevent pregnancies among women of reproductive age with migratory experience living in HICs. Two researchers independently screened and extracted data from the articles. Findings were categorized by patient and health system level factors according to Levesque et al.'s framework of access to health care.

RESULTS: A total of 68 articles were included, about half (n = 32) from North America. The articles focused on the individual level rather than the health system level, including aspects such as women's contraceptive knowledge, the influence of culture and religion on accessing and using contraception, partner involvement, and differing health insurance coverage. On the health system level, the articles highlighted lack of information on contraceptive services, cultural (in)adequacy of services and communication aspects, contraceptives' side effects, as well as geographic availability and cost of services. The review further identified three articles reporting on interventions related to contraceptive counselling.

CONCLUSIONS: There is a lack of knowledge regarding how health systems impose obstacles to contraceptive services for women with migratory experience on an organizational level, as research has focused heavily on the individual level. This review's findings may serve as a foundation for further research and advances in policy and practice, specifically recommending early provision of health system related information and contraceptive education, engagement of male partners in contraceptive discourses, cultural competency training for healthcare professionals, and strengthening of interpretation services for contraceptive counselling.}, } @article {pmid39298990, year = {2024}, author = {Nicholls-Clow, R and Simmonds-Buckley, M and Waller, G}, title = {Avoidant/restrictive food intake disorder: Systematic review and meta-analysis demonstrating the impact of study quality on prevalence rates.}, journal = {Clinical psychology review}, volume = {114}, number = {}, pages = {102502}, doi = {10.1016/j.cpr.2024.102502}, pmid = {39298990}, issn = {1873-7811}, mesh = {Humans ; Prevalence ; *Avoidant Restrictive Food Intake Disorder ; }, abstract = {OBJECTIVES: The prevalence of Avoidant/Restrictive Food Intake Disorder (ARFID) is unclear. This paper is the first to present meta-analysis based estimates of the prevalence of ARFID, and to assess the impact of the quality of the research on these estimates.

DESIGN: A pre-registered (Prospero: CRD42023487621) systematic review and meta-analysis.

METHODS: PubMed, PsychInfo, Web of Science and CINAHL were searched (final date of retrieval 30th July 2024) for peer reviewed papers published between 2013 and 2024. Random-effects and quality effects meta-analyses were used to compute and compare prevalence estimates and to evaluate the impact of study quality on prevalence rates. Subgroups were also considered (gender, age group, clinical status). Loney et al.'s (1998) Critical Appraisal of the Health Research Literature: Prevalence or Incidence of a Health Problem scale was used to assign each study a quality score across three categories - methodological validity (six points); interpretation of results (one point); and applicability of the results (one point).

RESULTS: Twenty-six studies were identified (n = 122,861). Meta-analysis using random-effects indicated a prevalence of 11.14 % (95 % CI 8.16-14.5 %), whereas quality effects prevalence was 4.51 % (95 % CI 0.7-10.68 %). Similar contrasts were evident among subgroups.

CONCLUSIONS: Even taking the more conservative estimate of 4.51 %, this review demonstrates that ARFID is a common disorder, meriting further research and clinical and service developments. Future research needs to be more methodologically robust (larger samples; standardised diagnostic measures; clearer data presentation).}, } @article {pmid39298423, year = {2024}, author = {Roher, SIG and Martin, DH and Yu, Z and Pride, T and Amirault, M and Rand, JR and Benoit, AC}, title = {How Etuaptmumk/Two-Eyed Seeing is used in indigenous health research: A scoping review.}, journal = {PloS one}, volume = {19}, number = {9}, pages = {e0310247}, pmid = {39298423}, issn = {1932-6203}, mesh = {Humans ; *Health Services, Indigenous ; }, abstract = {Our scoping review sought to describe how Etuaptmumk or Two-Eyed Seeing is used and reported on in Indigenous health research. Using the JBI scoping review methodology, we extracted uses of Etuaptmumk/Two-Eyed Seeing from 83 articles and then categorized the reported uses of Etuaptmumk/Two-Eyed Seeing according to Huria et al.'s eight CONSIDER statement domains (governance, prioritization, relationships, methodologies, participation, capacity, analysis and interpretation, and dissemination). We found that while authors used Etuaptmumk/Two-Eyed Seeing in varied ways and at different stages of their research projects, characterizations of the guiding principle were often insufficiently described or overly simplified. This scoping review intends to contribute to a greater dialogue about how Etuaptmumk/Two-Eyed Seeing is conceptualized and used in Indigenous health research with the goal of encouraging more intentional reporting of the guiding principle.}, } @article {pmid39278337, year = {2024}, author = {Wan, H and Green, L and Myerson, J}, title = {Delayed monetary losses: Do different procedures and discounting measures assess the same construct?.}, journal = {Behavioural processes}, volume = {222}, number = {}, pages = {105101}, doi = {10.1016/j.beproc.2024.105101}, pmid = {39278337}, issn = {1872-8308}, mesh = {Humans ; *Delay Discounting/physiology ; Male ; Female ; Adult ; *Reward ; Young Adult ; *Choice Behavior/physiology ; Surveys and Questionnaires ; Adolescent ; }, abstract = {The present study examined two procedures for assessing the discounting of delayed, hypothetical, monetary losses: the Adjusting-Amount procedure (Estle et al., 2006) and the Delayed Losses Questionnaire (Myerson et al., 2017), which was modeled on Kirby et al.'s (1999) delayed reward Monetary Choice Questionnaire. Of interest was whether these two procedures assess the same underlying construct. Online participants (N = 431) completed both the Adjusting-Amount procedure and the Delayed Losses Questionnaire. Results revealed that regardless of the delayed amount and whether the discounting measure used was atheoretical (area under the curve and immediate-choice proportion) or theoretically based (log k), the discounting on the Adjusting-Amount procedure was highly correlated with the discounting on the Delayed Losses Questionnaire (all r > .72). In addition, most of the participants (72.2 %) who showed one type of discounting pattern on one procedure (e.g., who increased choice of the larger payment with increases in its delay or who always chose the immediate payment) showed the same pattern on the other procedure. These findings are consistent with the hypothesis that the loss discounting procedures and measures studied here all assess the same construct.}, } @article {pmid39268672, year = {2024}, author = {Dickie, M and Serrouya, R and Becker, M and DeMars, C and Noonan, MJ and Steenweg, R and Boutin, S and Ford, AT}, title = {The influence of habitat alteration is widespread, but the impact of climate cannot continue to be discounted.}, journal = {Global change biology}, volume = {30}, number = {9}, pages = {e17497}, doi = {10.1111/gcb.17497}, pmid = {39268672}, issn = {1365-2486}, support = {//Regional Industry Caribou Collaboration/ ; }, mesh = {Animals ; *Ecosystem ; *Climate Change ; *Deer/physiology ; Population Density ; Conservation of Natural Resources ; }, abstract = {In Dickie et al. (2024), we contrasted the effects of climate and habitat alteration on white-tailed deer density, recognizing the role of both these factors. Barnas et al.'s (2024) critique raised concerns about data transformations, model overfitting, and inference methods, but our analysis demonstrates that these criticisms are either unfounded or align with our original conclusions. We reaffirm that while both climate and habitat alteration contribute to deer densities, management decisions cannot ignore the strong role of climate, which is only predicted to increase in coming decades.}, } @article {pmid39269809, year = {2025}, author = {Solen, M and Sultana, N and Lukes, L and Munzner, T}, title = {DeLVE into Earth's Past: A Visualization-Based Exhibit Deployed Across Multiple Museum Contexts.}, journal = {IEEE transactions on visualization and computer graphics}, volume = {31}, number = {1}, pages = {952-961}, doi = {10.1109/TVCG.2024.3456174}, pmid = {39269809}, issn = {1941-0506}, abstract = {While previous work has found success in deploying visualizations as museum exhibits, it has not investigated whether museum context impacts visitor behaviour with these exhibits. We present an interactive Deep-time Literacy Visualization Exhibit (DeLVE) to help museum visitors understand deep time (lengths of extremely long geological processes) by improving proportional reasoning skills through comparison of different time periods. DeLVE uses a new visualization idiom, Connected Multi-Tier Ranges, to visualize curated datasets of past events across multiple scales of time, relating extreme scales with concrete scales that have more familiar magnitudes and units. Museum staff at three separate museums approved the deployment of DeLVE as a digital kiosk, and devoted time to curating a unique dataset in each of them. We collect data from two sources, an observational study and system trace logs. We discuss the importance of context: similar museum exhibits in different contexts were received very differently by visitors. We additionally discuss differences in our process from Sedlmair et al.'s design study methodology which is focused on design studies triggered by connection with collaborators rather than the discovery of a concept to communicate. Supplemental materials are available at: https://osf.io/z53dq/.}, } @article {pmid39268456, year = {2024}, author = {Eftekhari, A and Baghian, N and Yoshany, N and Dehghan Moori Abadi, F and Jambarsang, S and Dehghani, MH and Askari, R}, title = {Predictors of performing preventive behaviors against affliction with COVID-19 based on vaccination: An application of the health belief model.}, journal = {Journal of education and health promotion}, volume = {13}, number = {}, pages = {187}, pmid = {39268456}, issn = {2277-9531}, abstract = {BACKGROUND: Nowadays, the COVID-19 pandemic has become one of the greatest global threats to human communities. Presently, the most important solution to deal with this pandemic is to fully comply with health protocols along with general vaccination. Given the increased vaccination rate in the community and the change in the thought of some people in the field of durable immunity and changing health behaviors, the present study determined the predictors of preventive behaviors against affliction with COVID-19 in two vaccinated and non-vaccinated groups based on the health belief model in the Iranian population aged 15-65 years.

MATERIALS AND METHODS: This descriptive-analytical study was conducted cross-sectionally in 2022. A sample size of 500 Yazdi citizens was selected using the convenience non-random sampling method using the contact numbers received from the SIB system of the Iranian health deputy. They were examined online in two vaccinated and unvaccinated groups. The instrument used was Delshad Noghabi et al.'s questionnaire which was based on the health belief model. Due to the adjustment of the questionnaire according to the target group, its validity and reliability were re-checked and confirmed. Data were analyzed with SPSS22 using descriptive and analytical statistics, t-test, and linear regression.

RESULTS: Based on the findings of the study, a significant difference was observed between the three variables of income level (P = 0.019), smoking (P <0.001), and employment status (P = 0.025) in two vaccinated and unvaccinated groups at the level of preventive behaviors. Besides, the constructs of perceived sensitivity (P <0.001), perceived benefits (P <0.001), action guide (P <0.001), and self-efficacy (P = 0.018) significantly predict preventive behaviors, so that the predictive value of perceived benefits (β =3.67) was more than other variables.

CONCLUSION: To prevent diseases, it is very important to increase people's awareness and information (self-efficacy) about the use of vaccination and pay attention to individual demographic characteristics in vaccination programs. Also, perceived sensitivity, perceived benefits, action guidelines, and perceived self-efficacy can be considered as important factors in determining people's willingness to be vaccinated. Therefore, education and information programs should be focused on these factors to increase people's willingness to be vaccinated.}, } @article {pmid39264656, year = {2025}, author = {Weinberg, JR and Cooper, JM}, title = {Providing LGBTQIA+ affirming mental health services in schools: A cultural adaptation of dialectical behavior therapy Skills Training for Emotional Problem Solving for Adolescents (DBT STEPS-A).}, journal = {School psychology (Washington, D.C.)}, volume = {40}, number = {2}, pages = {159-172}, doi = {10.1037/spq0000665}, pmid = {39264656}, issn = {2578-4226}, mesh = {Humans ; Adolescent ; *Sexual and Gender Minorities/psychology ; *Dialectical Behavior Therapy/methods ; *Problem Solving ; Schools ; *Mental Health Services ; Curriculum ; *School Mental Health Services ; *Emotions ; Female ; Male ; *School Health Services ; }, abstract = {Despite growing concerns related to the youth mental health crisis and the well-being of sexual and gender minority youth, specifically, most mental health interventions fail to meet the unique needs of this population. Research and clinical guidance have recommended that approaching mental health treatments through a lens of minority stress and intersectionality can be particularly helpful in addressing the mental health concerns of LGBTQIA+ (lesbian, gay, bisexual, transgender, questioning/queer, intersex, and asexual, with the '+' capturing other identities within the gender and sexually diverse population) youth. Because many adolescents do not have access to mental health care, schools have an important role to play in meeting the mental health needs of LGBTQIA+ youth. To address these issues, we propose LGBTQIA+ affirming adaptations to the dialectical behavior therapy (DBT) Skills Training for Emotional Problem Solving for Adolescents (STEPS-A) curriculum using Pachankis et al.'s (2023) Adaptation Model to provide practitioners with a culturally affirming model of this social-emotional curriculum, while highlighting the utility of this framework in adapting other evidence-based interventions in schools. We walk readers through each module of DBT STEPS-A and provide rationale for adapting these skills for LGBTQIA+ youth. We offer specific adaptations that facilitators can make through psychoeducation and skills training. For example, we provide sample dialectics that mirror the experience of minority stress and propose examples of coping skills that are relevant for LGBTQIA+ youth (e.g., distracting and self-soothing to tolerate distress). Finally, the role of school psychologists in meeting the mental health needs of LGBTQIA+ youth is discussed along with implications for practice and future research. (PsycInfo Database Record (c) 2025 APA, all rights reserved).}, } @article {pmid39263965, year = {2025}, author = {Brisson, R and Adayeva, A and Abdrakhmanova, S}, title = {Gender differences in adolescents' life satisfaction: A replication study in Kazakhstan.}, journal = {Journal of adolescence}, volume = {97}, number = {1}, pages = {301-309}, doi = {10.1002/jad.12404}, pmid = {39263965}, issn = {1095-9254}, mesh = {Humans ; Female ; Kazakhstan ; Male ; *Personal Satisfaction ; Adolescent ; Cross-Sectional Studies ; Sex Factors ; }, abstract = {INTRODUCTION: Whether adolescents' life satisfaction varies with gender is unclear. In a recently published study, Brisson et al. found unadjusted mean scores of life satisfaction to be higher in boys than in girls in Luxembourg, a country ranking high in gender-equality indexes. However, gender was no longer predictive of life satisfaction when well-identified predictors of life satisfaction were included in the model. The present work aimed to replicate Brisson et al.'s study in Kazakhstan, a less gender-equal country than Luxembourg, and test the gender-equality-paradox hypothesis.

METHODS: We used cross-sectional data from the Health-Behavior in School-aged Children study conducted in 2022 to mirror Brisson et al.'s study design. We relied on a nationally representative sample of 7369 school attendees in Kazakhstan (MAGE = 13.4; SDAGE = 1.7; 52.3% female). We performed general linear modeling analyses to achieve our research goals.

RESULTS AND CONCLUSIONS: In keeping with Brisson et al.'s study, we found unadjusted mean scores of life satisfaction to be higher in boys than in girls. The magnitude of the gender gap was lower in Kazakhstan than in Luxembourg. In contrast to Brisson et al.'s study, controlling for well-identified predictors of life satisfaction did not annul the gap in question but changed its sign. This result suggests that, ceteris paribus, girls were more satisfied with their life than boys. Overall, our replication study supports the gender-equality-paradox hypothesis. Future studies may investigate whether this paradox stems from gendered criteria of life satisfaction assessment and/or sociobiological differences in health profiles.}, } @article {pmid39261852, year = {2024}, author = {Nakhostin-Ansari, A}, title = {Does lecture playback speed not affect memory and concentration in medical students?.}, journal = {BMC medical education}, volume = {24}, number = {1}, pages = {993}, pmid = {39261852}, issn = {1472-6920}, mesh = {Humans ; *Students, Medical/psychology ; *Memory ; Learning ; Attention ; Education, Medical, Undergraduate ; Teaching ; }, abstract = {Merhavy et al.'s study on the impact of lecture playback speeds on concentration and memory is valuable as it is one of the few studies on how different playback speeds may affect medical students' learning. However, despite the novelty of this study, some limitations concerning its methodological rigor, including statistical analyses, lack of evaluation of confounders, unclear characteristics of participants, and lack of a true control group, need to be considered in the interpretation of findings.}, } @article {pmid39258748, year = {2025}, author = {Seo, H and Park, S and Kim, S and Lee, S and Choi, C}, title = {RETRACTED: Evaluating cardiac risks of TASER: An in-depth case study through probable current analysis.}, journal = {Journal of forensic sciences}, volume = {70}, number = {3}, pages = {e1-e5}, doi = {10.1111/1556-4029.15614}, pmid = {39258748}, issn = {1556-4029}, support = {NFS2024FSA02//National Forensic Service/ ; }, mesh = {Humans ; *Ventricular Fibrillation/etiology ; *Conducted Energy Weapon Injuries/complications ; Fatal Outcome ; Electric Impedance ; Risk Assessment ; Republic of Korea ; Male ; }, abstract = {This study investigates the cardiac safety concerns related to TASER discharges centering on a pivotal case that marked the first TASER-related fatality in South Korea. Employing Pratt et al.'s theoretical framework, the research evaluates the potential for ventricular fibrillation (VF) from these discharges. The methodology incorporated a high-resolution waveform analysis using sophisticated equipment and considered specific incident details, including dart impact locations verified through a forensic examination. A human body impedance of 500 Ω, chosen based on empirical studies and coupled with non-inductive resistance for high-voltage handling, was utilized in the model. By applying a heart-current factor from IEC 60479 standards, the study found a VF risk of up to 5% depending on the impact location and current pathways. In this specific case, although the calculated risk did not exceed critical thresholds, the VF risk was high enough to suggest that TASER discharges played a role in the fatal outcome. This study underscores the importance of dart impact location in TASER safety evaluations, contributing to a broader understanding of TASER cardiac risks and providing a basis to advocate for rigorous safety protocols.}, } @article {pmid39256473, year = {2024}, author = {Wang, Y and Ji, Z and Xu, B and Li, S and Xie, Y}, title = {The incidence of acute exacerbation of idiopathic pulmonary fibrosis: a systematic review and meta-analysis.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {21080}, pmid = {39256473}, issn = {2045-2322}, support = {No.212300410056//The Natural Science Foundation of Henan Youth Fund/ ; No.81830116//National Natural Science Foundation of China/ ; HSRP-DFCTCM-2023-3-16//Henan Province Scientific Research Project - Double First-Class Traditional Chinese medicine/ ; DFCTCM-2023-4-05//Henan Province Scientific Research Project - Double First-Class Traditional Chinese medicine/ ; 2023ZY2055//Special Project of Traditional Chinese Medicine Research of Henan Province/ ; No. LHGJ20220586//The Henan Province Medical Science and Technology Program/ ; 2021 No. 15//Henan Province Second Batch of Top-notch Chinese Medicine Talent Projects/ ; No. 2023YFC3502601//The National Key Research and development Program/ ; }, mesh = {Humans ; *Disease Progression ; *Idiopathic Pulmonary Fibrosis/epidemiology/therapy ; Incidence ; Prognosis ; Risk Factors ; }, abstract = {Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial lung disease with a high incidence of acute exacerbation and an increasing mortality rate. Currently, treatment methods and effects are limited. Therefore, we conducted a meta-analysis of the incidence of acute exacerbation in patients with IPF, hoping to provide reference for the prevention and management of IPF. We systematically searched the PubMed, Embase, Cochrane Library and Web of Science databases. From the creation of the database to the cohort study on April 3, 2023, we collected studies on the incidence of acute exacerbation of IPF patients, and used Stata software (version 16.0) for meta analysis. We used the Newcastle Ottawa Quality Assessment Scale (NOS) to assess the risk of bias for each study. We calculated the incidence of acute exacerbation in IPF patients and analyzed the risk factors for acute exacerbation in IPF patients and prognostic factors for overall survival from the initial IPF diagnosis. A total of ten cohort studies on the incidence of AE-IPF were included, including 11,855 IPF patients. The results showed that the incidence of acute exacerbation within one year was 9%; the incidence of acute exacerbation within 2 years is 13%; the incidence of acute exacerbation within 3 years is 19%; the incidence of acute exacerbation within 4 years is 11%. In addition, one study reported an acute exacerbation rate of 1.9% within 30 days. The incidence of acute exacerbation within ten years reported in one study was 9.8%. Mura et al.'s article included a retrospective cohort study and a prospective cohort study. The prospective cohort study showed that the incidence of acute exacerbation within 3 years was 18.6%, similar to the results of the retrospective cohort study meta-analysis. Our system evaluation and meta-analysis results show that the incidence of AE-IPF is relatively high. Therefore, sufficient attention should be paid to the research results, including the management and prevention of the disease, in order to reduce the risk of AE.Trial registration: PROSPERO, identifier CRD42022341323.}, } @article {pmid39250271, year = {2024}, author = {Lo Coco, G and Kivlighan, DM and Di Blasi, M and Giordano, C and Giannone, F and Gullo, S}, title = {The social microcosm revisited: A replication of Kivlighan et al. (2021) on the reciprocal relationship between in-session and intersession intimate behaviors.}, journal = {Journal of counseling psychology}, volume = {71}, number = {6}, pages = {583-595}, doi = {10.1037/cou0000739}, pmid = {39250271}, issn = {0022-0167}, mesh = {Humans ; Female ; Male ; Adult ; *Interpersonal Relations ; Young Adult ; Students/psychology ; Psychotherapy, Group/methods ; Italy ; Sexual Partners/psychology ; }, abstract = {The present study represents a replication and extension of Kivlighan et al.'s (2021) study, focusing on the social microcosm hypothesis, which posits that group members' interpersonal relationships, operationalized by intimate behaviors such as expressing anger or caring, inside the group, mirror their interpersonal relationships outside of the group. We examined the reciprocal associations between a group member's (e.g., actors) and the other group members' (e.g., partners) in-session and intersession intimate behaviors. The participants were 122 Italian graduate students (89.3% identifying as women) participating in eight-session interpersonal growth groups led by six experienced group therapists. Before each session group members completed the Interpersonal Relations Scale Checklist (Shadish, 1984) indicating their intersession intimate behaviors in the previous week. After each session group members completed the Interpersonal Relations Scale Checklist indicating their own in-session intimate behaviors. We used dynamic structural equation modeling to examine the reciprocal, temporal associations among group members' intersession and in-session intimate behaviors. The replication hypotheses were not confirmed. However, when partners engaged in higher than average intersession intimate behaviors in the previous week, then actors engaged in more in-session intimate behaviors in the current session. In addition, when actors and partners engaged in higher than average in-session intimate behaviors in the previous session, then actors engaged in significantly more intersession intimate behaviors in the current week. The results provide partial support for social microcosm theory, which predicts a reciprocal relationship for in-session and intersession intimate behaviors. As described above, there was a reciprocal relationship for partners' but not for actors' intimate behaviors. (PsycInfo Database Record (c) 2024 APA, all rights reserved).}, } @article {pmid39246238, year = {2024}, author = {Stock, NM and Blaso, D and Hotton, M}, title = {Caring for a Child with a Cleft Lip and/or Palate: A Narrative Review.}, journal = {The Cleft palate-craniofacial journal : official publication of the American Cleft Palate-Craniofacial Association}, volume = {}, number = {}, pages = {10556656241280071}, doi = {10.1177/10556656241280071}, pmid = {39246238}, issn = {1545-1569}, abstract = {Raising a child with healthcare needs places additional demands on caregivers. In 2012, Nelson and colleagues authored a review of 57 papers pertaining to parents' experiences of caring for a child with cleft lip and/or palate (CL/P). Thanks in large part to this review, available literature on this topic has grown considerably. The aim of the present review was to update and critically appraise recent literature, with the wider goal of assessing progress in the field and setting recommendations for future work. All original, peer-reviewed articles pertaining to the psychological adjustment of parents of children with CL/P living in high-income countries (published May 2009 to May 2024) were examined. A total of 126 articles were included. Findings were narratively synthesised according to three salient themes: Emotional Impact; Social Experiences; and Care Delivery. Recent research has built on Nelson et al.'s recommendations, addressing some prior gaps in knowledge. Nonetheless, some areas remained largely unexplored and critical methodological limitations were still evident. Recommendations for clinical practice include: improved informational resources for parents and non-specialist health professionals, regular audit of services in collaboration with parents and families, routine psychological screening for known risk factors and integrated psychological support from diagnosis onward. Recommendations for future research include the design of multicentre, prospective, longitudinal studies with sufficient sample sizes and appropriate control/reference groups, inclusion of families from diverse ethnic and socioeconomic backgrounds, further examination of factors contributing to psychological growth, the development and evaluation of psychological interventions, and cross-condition learning.}, } @article {pmid39241342, year = {2024}, author = {Bioy, A and Lignier, B and Servillat, T}, title = {The development of the therapeutic alliance during the first five hypnotherapy sessions.}, journal = {Complementary therapies in clinical practice}, volume = {57}, number = {}, pages = {101894}, doi = {10.1016/j.ctcp.2024.101894}, pmid = {39241342}, issn = {1873-6947}, mesh = {Humans ; *Hypnosis/methods ; *Therapeutic Alliance ; Male ; Female ; Adult ; Surveys and Questionnaires ; Middle Aged ; Young Adult ; Professional-Patient Relations ; }, abstract = {The therapeutic alliance is a principal element that allows the dynamics and effects of psychotherapy to be analyzed. In the past half-century, many studies have explored various psychotherapeutic approaches, including psychoanalytic, cognitive-behavioral and systemic psychotherapy, but hypnotherapy has not been addressed. This article presents the first analysis using current methods of verifying and understanding the dynamics of change in hypnotherapy, regarding to the therapeutic alliance. Luborsky et al.'s (1996) revised Helping Alliance Questionnaire (HAq-II) was administered to 59 patients in treatment with psychologists and psychiatrists using Ericksonian hypnosis. Our results suggest that the dynamics of the alliance in the first sessions of hypnotherapy involve factors related more to the therapist's adjustment to the patient than to the progress the patient makes in these initial sessions.}, } @article {pmid39241269, year = {2025}, author = {Doty, S and Petitt, JC and Kashkoush, A and Whiting, BB and Xiao, T and Francis, JJ and Gunzler, D and Roach, MJ and Kelly, ML}, title = {Novel application of latent class analysis to outcome assessment in traumatic brain injury with multiple injury subtypes or poly-TBI.}, journal = {Journal of neurosurgery}, volume = {142}, number = {2}, pages = {561-568}, doi = {10.3171/2024.5.JNS232842}, pmid = {39241269}, issn = {1933-0693}, mesh = {Humans ; *Brain Injuries, Traumatic/mortality/classification/therapy/complications ; Male ; *Latent Class Analysis ; Female ; Middle Aged ; Retrospective Studies ; Adult ; *Outcome Assessment, Health Care/methods ; Aged ; *Multiple Trauma/mortality/classification/therapy ; Hospital Mortality ; Glasgow Coma Scale ; Registries ; Withholding Treatment ; }, abstract = {OBJECTIVE: The aim of this study was to stratify poly-traumatic brain injury (poly-TBI) patterns into discrete classes and to determine the association of these classes with mortality and withdrawal of life-sustaining treatment (WLST).

METHODS: The authors performed a single-center retrospective review of their institutional trauma registry from 2018 to 2020 to identify patients with traumatic brain injury (TBI). Patients were included if they had moderate to severe TBI, defined as Glasgow Coma Scale score ≤ 12 and Abbreviated Injury Scale (AIS) head score ≥ 3, and the presence of more than one TBI subtype. TBI subtypes were defined as subdural hemorrhage (SDH), subarachnoid hemorrhage (SAH), intracerebral hemorrhage (ICH), and epidural hemorrhage (EDH). Latent class analysis was used to identify patient classes based on TBI subtypes and Rotterdam CT (RCT) scores. The authors then evaluated class membership in relation to categorical outcomes of in-hospital mortality and WLST by using Lanza et al.'s method.

RESULTS: A total of 125 patients met inclusion criteria for poly-TBI. Latent class analysis yielded 3 poly-TBI classes: class 1-mixed; class 2-SDH/SAH; and class 3-EDH/SAH. Class 1-mixed had a higher likelihood of SDH, SAH, and ICH, and a lower likelihood of EDH. Class 2-SDH/SAH had a higher likelihood of only SDH and SAH. Class 3-EDH/SAH had a higher likelihood of EDH and SAH, and a lower likelihood of SDH and ICH. Class 1-mixed was relatively more likely to have an RCT score of 2. Class 2-SDH/SAH was relatively more likely to have an RCT score of 2, 3, and 4. Class 3-EDH/SAH had a higher likelihood of an RCT score of 3, 4, and 5. Class 1-mixed had significantly lower mortality (χ2 = 7.968; p = 0.005) and less WLST (χ2 = 4.618; p = 0.032) than Class 2-SDH/SAH. Class 2-SDH/SAH had the highest probability of death (0.612), followed by class 3-EDH/SAH (0.385) and class 1-mixed (0.277). Similarly, class 2-SDH/SAH had the highest WLST probability (0.498), followed by class 3-EDH/SAH (0.615) and class 1-mixed (0.238).

CONCLUSIONS: Distinct poly-TBI classes were associated with increased in-hospital mortality and WLST. Further research with larger datasets will allow for more comprehensive poly-TBI class definitions and outcomes analysis.}, } @article {pmid39236524, year = {2024}, author = {Campos, TAM and Anjos, LAD and Wady, MTB and Wahrlich, V}, title = {Measured and predicted resting metabolic rate in patients with inflammatory bowel disease.}, journal = {Nutrition (Burbank, Los Angeles County, Calif.)}, volume = {127}, number = {}, pages = {112552}, doi = {10.1016/j.nut.2024.112552}, pmid = {39236524}, issn = {1873-1244}, mesh = {Humans ; *Basal Metabolism/physiology ; Male ; Female ; Adult ; *Calorimetry, Indirect/methods ; Middle Aged ; *Body Composition ; *Inflammatory Bowel Diseases/metabolism/physiopathology ; Colitis, Ulcerative/physiopathology/metabolism ; Crohn Disease/metabolism/physiopathology ; Young Adult ; }, abstract = {OBJECTIVE: The present study aimed to compare measured and estimated resting metabolic rate (RMR) predicted by selected equations in patients with nonactive inflammatory bowel disease (IBD) on an outpatient university clinic regimen.

Seventy-two adult (≥20 years) IBD patients (45 with Crohn's disease-CD) had RMR measured (mRMR) by indirect calorimetry and also estimated by predictive equations (Cunningham, Henry, Anjos et al., and Marra et al.). Body composition was assessed by DXA. Absolute Bias (estimated - mRMR) and % Bias (Bias/mRMR) were calculated. Agreement was assessed as the limit of agreement (LoA) in the Bland & Altman approach.

RESULTS: There was no difference in age, body composition and mRMR between individuals with CD (5414.2 ± 1023.7 kJ/day) and ulcerative colitis (5443.9 ± 1008.9 kJ/day). Among the equations, only the Anjos et al.'s population-specific equation (-52.1 [642.0] kJ/day, P = 0.493; LoA: -1311; 1206 kJ/d) accurately estimated RMR. The equations of Marra et al. produced the highest % Bias (24.1 ± 14.8%). The Bland & Altman plots showed that the range of the LoA was relatively similar for all equations. In the simple regression analysis, the model with FFM resulted in a higher coefficient of determination (R[2] = 0.51 for DC 0.74 for UC) compared to the model that included BM (R[2] = 0.35 for DC and 0.65 for UC).

CONCLUSIONS: Among the equations analyzed, only Anjos et al.'s accurately estimated RMR in outpatients with nonactive IBD. However, caution is advised when applying it at the individual level, due to the wide observed LoA.}, } @article {pmid39226000, year = {2024}, author = {Bartlett, VL}, title = {Safety in Numbers and Other Questions from Pierson et al.'s Bioethics Survey.}, journal = {The American journal of bioethics : AJOB}, volume = {24}, number = {9}, pages = {53-55}, doi = {10.1080/15265161.2024.2377102}, pmid = {39226000}, issn = {1536-0075}, mesh = {Humans ; *Bioethics ; Surveys and Questionnaires ; }, } @article {pmid39213875, year = {2024}, author = {Antonio, ICF and Lee, PH}, title = {'What if I get sick?' Healthcare (non)decisions of overseas Filipino workers in Taiwan.}, journal = {Social science & medicine (1982)}, volume = {358}, number = {}, pages = {117268}, doi = {10.1016/j.socscimed.2024.117268}, pmid = {39213875}, issn = {1873-5347}, mesh = {Humans ; Taiwan ; Philippines/ethnology ; Female ; Male ; Adult ; *Patient Acceptance of Health Care/psychology ; Transients and Migrants/psychology/statistics & numerical data ; Decision Making ; Health Services Accessibility ; Qualitative Research ; }, abstract = {The increasing presence of overseas Filipino workers (OFWs) in Taiwan, particularly in the electronics and technology (E&T) industry, has raised concerns about their health and health-seeking behaviours. Our study draws on a theoretical framework combining Brandenberger et al.'s 3C model, which considers challenges in communication, continuity of care, and confidence regarding healthcare delivery for migrant workers, with Scott's sociology of nothing. This framework enables us to interpret the decisions of OFWs on seeking care, not seeking care, or not making any decision. Although the National Health Insurance covers migrant workers and the New South Bound Policy commits to promoting migrant health, narrative accounts of individual workers, migrant rights advocates, and shelter organisers inform us of OFWs' ambivalence towards utilising the healthcare resources available. The decisions made by OFWs in the E&T industry may include seeking assistance, not seeking assistance, or not addressing health concerns due to legal, financial, or cultural reasons. The contextual nuances behind their decisions led us to look beyond the challenges they face and argue for interventions such as peer education on legal rights awareness and health literacy to enable OFWs to make informed decisions about their well-being.}, } @article {pmid39203722, year = {2024}, author = {Park, SG and Kim, H}, title = {Lack of Association between Insufficient Intake of Multiple Vitamins and Frailty in Older Adults Who Consume Sufficient Energy and Protein: A Nationwide Cross-Sectional Study.}, journal = {Nutrients}, volume = {16}, number = {16}, pages = {}, pmid = {39203722}, issn = {2072-6643}, mesh = {Humans ; Aged ; Female ; Male ; *Frailty/epidemiology ; Cross-Sectional Studies ; *Vitamins/administration & dosage ; *Energy Intake ; *Dietary Proteins/administration & dosage ; *Frail Elderly/statistics & numerical data ; Republic of Korea/epidemiology ; Aged, 80 and over ; Nutrition Surveys ; Nutritional Status ; Prevalence ; }, abstract = {Frailty is a complex condition that intensifies with age and is marked by decreased physiological function. We rigorously investigated the effects of lower vitamin intake on frailty using data from 665 adults aged over 65 years who consumed sufficient recommended daily energy and protein intakes from the Korean Nutrition and Health Survey, 2016-2019. The definition of frailty was modified based on Fried et al.'s definition of weight loss, exhaustion, weakness, slowness, and low energy expenditure. Based on daily intake, we analyzed vitamins such as vitamin A, thiamine, riboflavin, niacin, folic acid, and vitamin C. Our results of logistic regression showed that increasing multiple deficiencies in several kinds of vitamins (mild to moderate to severe) is not associated with frailty (odds ratio: 1, 1.24 (0.24-3.10), 0.82 (0.28-2.39), p for trend = 0.626) in older adults who consumed sufficient calories and proteins. A subgroup analysis of age and sex, which may interfere with the relationship between vitamin intake and frailty, showed that vitamin intake was not associated with frailty when sufficient energy and proteins were consumed. Furthermore, there was no difference in the prevalence of frailty between the groups with sufficient and insufficient intakes of individual vitamins.}, } @article {pmid39203208, year = {2024}, author = {Liao, M and Zhang, K and Luo, C and Wu, G and Zeng, H}, title = {In-Situ Sulfuration of CoAl Metal-Organic Framework for Enhanced Supercapacitor Properties.}, journal = {Materials (Basel, Switzerland)}, volume = {17}, number = {16}, pages = {}, pmid = {39203208}, issn = {1996-1944}, support = {52203285//National Natural Science Foundation of China/ ; 2023JJ40732//Natural Science Foundation of Hunan Province/ ; }, abstract = {Designing efficient electrode materials is necessary for supercapacitors but remains highly challenging. Herein, cobalt sulfide with crystalline/amorphous heterophase (denoted as Co(Al)S) derived from an Al metal-organic framework was constructed by ion exchange/acid etching and subsequent sulfidation strategy. It was found that rational sulfidation by adjusting the sulfur source concentration to a suitable level was favorable to form a 3D nanosheet-interconnected network architecture with a large specific surface area, which promoted ion/electron transport and charge separation. Benefiting from the features of the unique network structure and heterophase accompanied by aluminum, nitrogen and carbon coordinated in amorphous phase, the optimal Co(Al)S(10) exhibited a high specific capacity (1791.8 C g[-1] at 1 A g[-1]), an outstanding rate capability and an excellent cycling stability. Furthermore, the as-assembled Co(Al)S//AC device afforded an energy density of 72.3 Wh kg[-1] at a power density of 750 W kg[-1], verifying that the Co(Al)S was a promising material for energy storage devices. The developed scheme is expected to promote the application of MOF-derived electrode materials in electrochemical energy storage and conversion fields.}, } @article {pmid39201947, year = {2024}, author = {Festa, F and Festa, M and Medori, S and Perrella, G and Valentini, P and Bolino, G and Macrì, M}, title = {Midpalatal Suture Maturation in Relation to Age, Sex, and Facial Skeletal Growth Patterns: A CBCT Study.}, journal = {Children (Basel, Switzerland)}, volume = {11}, number = {8}, pages = {}, pmid = {39201947}, issn = {2227-9067}, abstract = {BACKGROUND: The evaluation of midpalatal suture maturation is essential to undertake the most predictable maxillary expansion approach. Several factors, such as age, gender, and facial growth patterns, seem to be involved in midpalatal suture staging and, consequently, in its opening; however, the link between these variables and the stages of midpalatal suture development remains poorly understood. Our study aimed to analyse the midpalatal suture maturation in relation to age, sex, and skeletal growth patterns by CBCT.

METHODS: We enrolled 263 patients (119 males and 144 females) aged from 8 to 20 years. The midpalatal suture maturation was defined according to Angelieri et al.'s classification using a low-dose CBCT. The chi-square test and linear regression were applied to investigate the suture stages by age, sex, and vertical and sagittal growth patterns.

RESULTS: Stage A was present in 8- and 9-year-olds with a larger prevalence in boys, while the prevalence of stage E increased progressively with age. Stage D was the most prevalent in our sample. The statistical analysis described that stage A was more likely in the youngest subjects, and stage E in the oldest participants. The males tended to have lower maturation stages. Moreover, the hypodivergent and normodivergent subjects tended to have higher maturation stages, while Class III was more likely in subjects in stages D or E.

CONCLUSIONS: A total of 127 patients were in stages A, B, and C, showing an unfused suture. In young individuals, the opening of the midpalatal suture leads to a proper facial growth development by correcting the transverse superior hypoplasia. The midpalatal sutural maturation classification was related to age, sex, and divergence.}, } @article {pmid39200095, year = {2024}, author = {Marinello, D and Favero, C and Albetti, B and Barbuto, D and Vigna, L and Pesatori, AC and Bollati, V and Ferrari, L}, title = {Investigating the Relationship between Epigenetic Age and Cardiovascular Risk in a Population with Overweight/Obesity.}, journal = {Biomedicines}, volume = {12}, number = {8}, pages = {}, pmid = {39200095}, issn = {2227-9059}, support = {ERC-2011-StG 282413//European Research Council ERC Ideas/ ; }, abstract = {Introduction: Cardiovascular diseases stand as the leading global cause of mortality. Major modifiable risk factors encompass overweight/obese conditions, high blood pressure, elevated LDL cholesterol, diabetes, smoking, secondhand smoke exposure, unhealthy diet, and physical inactivity. In the present study, we explored the relationship between cardiovascular risk factors and epigenetic age (DNAm age), an estimate reflecting an individual's actual physiological functionality and overall health. Additionally, we assessed the association between DNAm age acceleration and cardiovascular risk, as evaluated through the Framingham risk score (FRS). Methods: The study includes 190 subjects with overweight/obese conditions. We calculated their DNAm age using Zbieć-Piekarska et al.'s DNAm age estimator on five sets of CpGs analyzed in the peripheral leucocytes. Linear regression models were employed to test the associations. Results: Various parameters contributing to increased cardiovascular risk were associated with DNAm age acceleration, such as systolic blood pressure (β = 0.045; SE = 0.019; p = 0.019), heart rate (β = 0.096; SE = 0.032; p = 0.003), blood glucose (β = 0.025; SE = 0.012; p = 0.030), glycated hemoglobin (β = 0.105; SE = 0.042; p = 0.013), diabetes (β = 2.247; SE = 0.841; p = 0.008), and menopausal conditions (β = 2.942; SE = 1.207; p = 0.016), as well as neutrophil (β = 0.100; SE = 0.042; p = 0.018) and granulocyte (β = 0.095; SE = 0.044; p = 0.033) counts. Moreover, DNAm age acceleration raised the FRS (∆% 5.3%, 95% CI 0.8; 9.9, p = 0.019). Conclusion: For the first time, we report that cardiovascular risk factors accelerated DNAm age in a selected population of hypersusceptible individuals with overweight or obesity. Our results highlight the potential of DNAm age acceleration as a biomarker of cumulative effects in cardiovascular risk assessment.}, } @article {pmid39198955, year = {2024}, author = {Leung, TCH and Snell, RS and Lee, D}, title = {Organisational learning through a charitable trust-initiated project focusing on end-of-life care.}, journal = {Journal of health organization and management}, volume = {38}, number = {6}, pages = {781-799}, doi = {10.1108/JHOM-01-2023-0019}, pmid = {39198955}, issn = {1758-7247}, mesh = {Hong Kong ; Humans ; *Terminal Care ; *Interviews as Topic ; *Charities ; Organizational Case Studies ; Qualitative Research ; Learning ; }, abstract = {PURPOSE: We identify lessons from a project sponsored by a large charitable trust, which sought to build capability for end-of-life (EOL) care in Hong Kong through interdisciplinary and multi-agency collaboration.

DESIGN/METHODOLOGY/APPROACH: An in-depth case study drawing on 21 in-depth interviews with diverse stakeholders was conducted. Lyman et al.'s (2018) model of organisational learning (OL) in healthcare settings was applied to analyse the relative emphasis on particular contextual factors and mechanisms, and to identify outcomes perceived to have been achieved.

FINDINGS: Infrastructure such as materials for assessment and education received the most emphasis among the contextual factors and deliberate learning such as training sessions received the greatest attention among the mechanisms. While perceptions indicated that desired outcomes were being achieved in terms of social impact, there were relatively few mentions of "soft" factors such as enhanced motivation, leadership or OL skills among staff.

ORIGINALITY/VALUE: This study extends the literature on how to create valuable social impact through OL. While prior studies have examined social impact in terms of solutions for social and environmental problems, ours is one of the few that examines how improvements are made to organisations' capability to deliver such impacts in the context of healthcare.}, } @article {pmid39198327, year = {2024}, author = {Wang, JY and Speechley, K and Anderson, KK and Gainham, G and Ali, S and Trottier, ED and Sabhaney, V and Heath, A and Sich, C and Forbes, A and Poonai, N}, title = {Intranasal midazolam for procedural distress in children in the emergency department: a systematic review and meta-analysis.}, journal = {CJEM}, volume = {26}, number = {9}, pages = {658-670}, pmid = {39198327}, issn = {1481-8043}, mesh = {Humans ; *Midazolam/administration & dosage ; *Administration, Intranasal ; *Emergency Service, Hospital ; Child ; Hypnotics and Sedatives/administration & dosage ; Pain, Procedural/prevention & control/etiology ; Child, Preschool ; Anti-Anxiety Agents/administration & dosage/therapeutic use ; Adolescent ; Infant ; }, abstract = {OBJECTIVES: Intranasal (IN) midazolam is the most common anxiolytic for children in the emergency department (ED), but evidence of benefit is conflicting. We synthesized the evidence on IN midazolam for procedural distress in children undergoing ED painful procedures.

METHODS: We included trials involving painful ED procedures in children 0-18 years involving IN midazolam. Primary outcome was procedural distress. We summarized results using Tricco et al.'s classification of "neutral" (p ≥ 0.05), "favorable," and "unfavorable" (p < 0.05), supporting IN midazolam or comparator, respectively, or "indeterminate" (unable to judge). Where possible, we pooled results using meta-analysis. Methodologic quality of evidence was evaluated using Cochrane Collaboration's risk of bias tool and GRADE system.

RESULTS: We included 41 trials (n = 2973 participants). Thirty trials involved intravenous insertion. IN midazolam was superior to placebo (RR = 7.2; 95% CI: 3.43, 15.25; 3 trials; I[2] = 0%). However, 56-90% of the IN midazolam group resisted the procedure. Focusing on the three trials that used validated measures, IN midazolam was "neutral" versus IN ketamine and either "neutral" or "unfavorable" versus IN dexmedetomidine. There was no difference in the proportion of children with a satisfactory distress score between IN midazolam and oral midazolam (RR = 1.1; 95% CI: 0.74, 1.73; 2 trials; I[2] = 53%), IN ketamine (RR = 1.1; 95% CI: 0.91, 1.25; 6 trials; I[2] = 0%), or IN dexmedetomidine (RR = 0.4; 95% CI: 0.17, 1.05; 3 trials; I[2] = 84%). Ten trials involved laceration repair. IN midazolam was "favorable" versus placebo; however, both groups scored in the anxious range. There was no difference in distress between IN midazolam and oral midazolam (SMD = 0.01; 95% CI:-0.32, 0.34; 2 trials; I[2] = 0%) (Fig. 3E) [64,65]. Using validated instruments, IN midazolam was "unfavorable" versus IN dexmedetomidine but "favorable" versus oral diazepam and placebo.

CONCLUSIONS: There is limited methodologically rigorous evidence that IN midazolam is better than placebo for IV insertion and laceration repair. At the doses studied, preliminary evidence suggests that IN dexmedetomidine may be superior to IN midazolam for both IV insertion and laceration repair.}, } @article {pmid39186645, year = {2024}, author = {Burunat, I and Levitin, DJ and Toiviainen, P}, title = {Breaking (musical) boundaries by investigating brain dynamics of event segmentation during real-life music-listening.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {121}, number = {36}, pages = {e2319459121}, pmid = {39186645}, issn = {1091-6490}, support = {346210//Research Council of Finland (AKA)/ ; }, mesh = {Humans ; *Music/psychology ; *Magnetic Resonance Imaging ; *Auditory Perception/physiology ; Male ; Adult ; Female ; *Brain/physiology/diagnostic imaging ; Brain Mapping/methods ; Young Adult ; Acoustic Stimulation ; }, abstract = {The perception of musical phrase boundaries is a critical aspect of human musical experience: It allows us to organize, understand, derive pleasure from, and remember music. Identifying boundaries is a prerequisite for segmenting music into meaningful chunks, facilitating efficient processing and storage while providing an enjoyable, fulfilling listening experience through the anticipation of upcoming musical events. Expanding on Sridharan et al.'s [Neuron 55, 521-532 (2007)] work on coarse musical boundaries between symphonic movements, we examined finer-grained boundaries. We measured the fMRI responses of 18 musicians and 18 nonmusicians during music listening. Using general linear model, independent component analysis, and Granger causality, we observed heightened auditory integration in anticipation to musical boundaries, and an extensive decrease within the fronto-temporal-parietal network during and immediately following boundaries. Notably, responses were modulated by musicianship. Findings uncover the intricate interplay between musical structure, expertise, and cognitive processing, advancing our knowledge of how the brain makes sense of music.}, } @article {pmid39184428, year = {2024}, author = {Venkatachalam, V and Pandiarajan, R and Meyappan, A and Anbukkarasu, H}, title = {Evaluation of Surgical Outcomes of Zygomatic Implant-Supported Rehabilitation of Atrophic Maxillary Arches - A Prospective Study.}, journal = {Annals of maxillofacial surgery}, volume = {14}, number = {1}, pages = {27-32}, pmid = {39184428}, issn = {2231-0746}, abstract = {INTRODUCTION: Prosthetic rehabilitation with implants in the atrophic edentulous maxilla often requires a bone augmentation procedure to enable implant placement and integration. However, rigid anchorage can also be achieved using long zygomatic implants. The aim of this study was to evaluate the surgical outcomes of rehabilitation of atrophic posterior maxillary ridges with zygomatic implants using the zygomatic success code (ZSC) and derive the success grade for the procedure based on the observed results.

MATERIALS AND METHODS: A total of eight implants were placed in an extrasinus technique based on the zygomatic anatomy-guided approach. The following were evaluated postoperatively - primary stability, maxillary sinus pathology, soft-tissue healing and prosthetic offset. The ZSC score was calculated, and success grading was given with ZSC based on Aparacio et al.,'s guidelines.

RESULTS: One implant had Grade 1 mobility and partial maxillary sinus opacification, 25% (n = 2) revealed a mild recession exposing the implant head and 12.5% (n = 1) showed significant recession up to 7 mm. The prosthetic offset of zygomatic implants was scored -1 for all eight implants. Five implants were given a success code of 1/1/1/1 and a success grade of Grade I, two implants were given code 1/1/2/1 with Grade II and one implant 2/2/3/1 and grade III. The results imply that zygomatic implants can be a successful option in maxillary rehabilitation.

DISCUSSION: The zygomatic implants, as a graft less and promising solution to the rehabilitation of atrophied maxillary arches, have excellent surgical outcomes with varied advantages.}, } @article {pmid39184100, year = {2024}, author = {Sikirzhytskaya, A and Tyagin, I and Sutton, SS and Wyatt, MD and Safro, I and Shtutman, M}, title = {AI-based mining of biomedical literature: Applications for drug repurposing for the treatment of dementia.}, journal = {Research square}, volume = {}, number = {}, pages = {}, doi = {10.21203/rs.3.rs-4750719/v1}, pmid = {39184100}, issn = {2693-5015}, support = {R01 DA054992/DA/NIDA NIH HHS/United States ; }, abstract = {Neurodegenerative pathologies such as Alzheimer's disease, Parkinson's disease, Huntington's disease, Amyotrophic lateral sclerosis, Multiple sclerosis, HIV-associated neurocognitive disorder, and others significantly affect individuals, their families, caregivers, and healthcare systems. While there are no cures yet, researchers worldwide are actively working on the development of novel treatments that have the potential to slow disease progression, alleviate symptoms, and ultimately improve the overall health of patients. Huge volumes of new scientific information necessitate new analytical approaches for meaningful hypothesis generation. To enable the automatic analysis of biomedical data we introduced AGATHA, an effective AI-based literature mining tool that can navigate massive scientific literature databases, such as PubMed. The overarching goal of this effort is to adapt AGATHA for drug repurposing by revealing hidden connections between FDA-approved medications and a health condition of interest. Our tool converts the abstracts of peer-reviewed papers from PubMed into multidimensional space where each gene and health condition are represented by specific metrics. We implemented advanced statistical analysis to reveal distinct clusters of scientific terms within the virtual space created using AGATHA-calculated parameters for selected health conditions and genes. Partial Least Squares Discriminant Analysis was employed for categorizing and predicting samples (122 diseases and 20889 genes) fitted to specific classes. Advanced statistics were employed to build a discrimination model and extract lists of genes specific to each disease class. Here we focus on drugs that can be repurposed for dementia treatment as an outcome of neurodegenerative diseases. Therefore, we determined dementia-associated genes statistically highly ranked in other disease classes. Additionally, we report a mechanism for detecting genes common to multiple health conditions. These sets of genes were classified based on their presence in biological pathways, aiding in selecting candidates and biological processes that are exploitable with drug repurposing.}, } @article {pmid39168920, year = {2024}, author = {Maxwell, NP and Huff, MJ and Hajnal, A and Namias, JM and Blau, JJC and Day, B and Marsh, KL and Meagher, BR and Shelley-Tremblay, JF and Thomas, GF and Wagman, JB}, title = {Affordance norms for 2825 concrete nouns.}, journal = {Behavior research methods}, volume = {56}, number = {8}, pages = {8480-8491}, pmid = {39168920}, issn = {1554-3528}, mesh = {Humans ; *Semantics ; Female ; Male ; Young Adult ; Adult ; Adolescent ; Psycholinguistics/methods ; }, abstract = {Objects are commonly described based on their relations to other objects (e.g., associations, semantic similarity, etc.) or their physical features (e.g., birds have wings, feathers, etc.). However, objects can also be described in terms of their actionable properties (i.e., affordances), which reflect interactive relations between actors and objects. While several normed datasets have been developed to categorize various aspects of meaning (e.g., semantic features, cue-target associations, etc.), to date, norms for affordances have not been generated. We address this limitation by developing a set of affordance norms for 2825 concrete nouns. Using an open-response format, we computed affordance strength (AFS; i.e., the probability of an item eliciting a particular action response), affordance proportion (AFP; i.e., the proportion of participants who provided a specific action response), and affordance set size (AFSS; i.e., the total number of unique action responses) for each item. Because our stimuli overlapped with Pexman et al.'s, Behavior Research Methods, 51, 453-466, (2019) body-object interaction norms (BOI), we tested whether AFS, AFP, and AFSS were related to BOI, as objects with more perceived action properties may be viewed as being more interactive. Additionally, we tested the relationship between AFS and AFP and two separate measures of relatedness: cosine similarity (Buchanan et al., Behavior Research Methods, 51, 1849-1863, 2019a, Behavior Research Methods, 51, 1878-1888, 2019b) and forward associative strength (Nelson et al., Behavior Research Methods, Instruments, & Computers, 36(3), 402-407, 2004). All analyses, however, revealed weak relationships between affordance measures and existing semantic norms, suggesting that affordance properties reflect a separate construct.}, } @article {pmid39157427, year = {2024}, author = {Behnke, M and Lakens, D and Petrova, K and Chwiłkowska, P and Białek, SJ and Kłoskowski, M and Krzyżaniak, W and Maciejewski, P and Kaczmarek, LD and Szymański, K and Jamieson, JP and Gross, JJ}, title = {Applying a synergistic mindsets intervention to an esports context.}, journal = {Royal Society open science}, volume = {11}, number = {6}, pages = {240691}, pmid = {39157427}, issn = {2054-5703}, abstract = {Affective responses during stressful, high-stakes situations can play an important role in shaping performance. For example, feeling shaky and nervous at a job interview can undermine performance, whereas feeling excited during that same interview can optimize performance. Thus, affect regulation-the way people influence their affective responses-might play a key role in determining high-stakes outcomes. To test this idea, we adapted a synergistic mindsets intervention (SMI) (Yeager et al. 2022 Nature 607, 512-520 (doi:10.1038/s41586-022-04907-7)) to a high-stakes esports context. Our approach was motivated by the idea that (i) mindsets both about situations and one's stress responses to situations can be shaped to help optimize stress responses, and (ii) challenge versus threat stress responses will be associated with improved outcomes. After a baseline performance task, we randomly assigned gamers (n = 300) either to SMI or a control condition in which they learned brain facts. After two weeks of daily gaming, gamers competed in a cash-prize tournament. We measured affective experiences before the matches and cardiovascular responses before and throughout the matches. Contrary to predictions, gamers did not experience negative affect (including feeling stressed), thus limiting the capacity for the intervention to regulate physiological responses and optimize performance. Compared with the control participants, synergistic mindsets participants did not show greater challenge responses or improved performance outcomes. Though our adaptation of Yeager et al.'s SMI did not optimize esports performance, our findings point to important considerations regarding the suitability of an intervention such as this to different performance contexts of varying degrees of stressfulness.}, } @article {pmid39152390, year = {2024}, author = {Phillip, E and Walsh, A and Jewitt, S and Elnakoury, F and Simon, J and Conroy, RM and Stanistreet, D}, title = {Exploring community-based participatory research for household and ambient air pollution projects: insights from key informants.}, journal = {BMC public health}, volume = {24}, number = {1}, pages = {2233}, pmid = {39152390}, issn = {1471-2458}, support = {COALESCE/2020/13//Irish Research Council for the Humanities and Social Sciences/ ; }, mesh = {Humans ; *Community-Based Participatory Research ; *Air Pollution/prevention & control ; Interviews as Topic ; Qualitative Research ; }, abstract = {BACKGROUND: Despite the extensive use of community-based participatory research (CBPR) in health-related projects, there is limited work on how CBPR processes result in outcomes, especially in household and ambient air pollution (HAAP) research. This study explores the reflections of key informants on factors that shape the implementation and outcomes of CBPR in HAAP projects.

METHODS: We conducted semi-structured interviews with 13 key stakeholders, including academic researchers, non-governmental organisation administrators, a policymaker, and community members. All interviewees have experience in CBPR projects. Interviews were analysed using framework analysis, and findings were mapped to Wallerstein et al.'s CBPR conceptual model, which consists of four constructs: context, partnership processes, intervention and research, and outcomes.

RESULTS: The findings are described under two main categories: 'barriers to participation' and 'good practices for effective CBPR design and implementation'. Relevant sub-categories were barriers at the structural, research, community, and individual levels. Suggestions for good practices included respect, cultural humility, trust, effective communication, suitable and affordable interventions such as improved cookstoves, appropriate participatory research tools, and gratuity for the community's time.

CONCLUSION: Key informants' perspectives identified factors supported by the CBPR model to inform the design and implementation of the CBPR approach. The add-ons to some of the model's factors, such as intra-community dynamics, give value to the informants' knowledge to support community-research partnerships and improve outcomes in HAAP intervention projects. Addressing these factors at the design stage and reporting CBPR evaluation could deepen the understanding of community-research partnerships.}, } @article {pmid39151910, year = {2025}, author = {Eymundsdottir, H and Blondal, BS and Geirsdottir, ÓG and Ramel, A}, title = {Poor Activities of Daily Living Predict Future Weight Loss in Older Adults After Hospital Discharge-Secondary Analysis of a Randomized Trial.}, journal = {Journal of aging and physical activity}, volume = {33}, number = {1}, pages = {42-50}, doi = {10.1123/japa.2023-0104}, pmid = {39151910}, issn = {1543-267X}, mesh = {Humans ; Aged ; *Activities of Daily Living ; *Weight Loss/physiology ; Female ; Male ; *Patient Discharge ; Aged, 80 and over ; *Nutrition Therapy ; Independent Living ; Malnutrition/prevention & control ; }, abstract = {This study examined whether participants with poor activities of daily living (ADLs) at hospital discharge had increased weight loss after 6 months of follow-up and whether nutrition therapy can prevent this weight loss. This dietary randomized controlled trial (N = 104) examined community-dwelling older adults (66-95 years) discharged from hospital and at risk for malnutrition, receiving either 6 months of nutrition therapy (intervention) or only standard care (control). ADL was assessed using seven questions on self-care based on the Katz et al.'s method. At discharge, 45 (43%), 36 (35%), and 23 (22%) had high, medium, and poor ADL, respectively, with no differences between the control and intervention groups according to chi-square test. Participants in the control group with poor ADL had significantly higher weight loss than participants with high ADL (age- and sex-adjusted analysis of covariance: 3.6 kg; 95% confidence interval [1.0, 6.1] kg, p = .007). No such difference was observed in the intervention group. Participants with poor ADL at hospital discharge develop lower body weight by around 3.5 kg 6 months later when compared with participants with high ADL. Receiving nutrition therapy could help older adults with poor ADL to maintain body weight after hospital discharge.}, } @article {pmid39151678, year = {2024}, author = {Li, D and Wang, Y and Weng, X}, title = {Response letter to Kaiqing Li et al.'s Commentary on "Efficacy and safety of Gutong Patch compared with NSAIDs for knee osteoarthritis: A real-world multicenter, prospective cohort study in China".}, journal = {Pharmacological research}, volume = {208}, number = {}, pages = {107351}, doi = {10.1016/j.phrs.2024.107351}, pmid = {39151678}, issn = {1096-1186}, mesh = {Humans ; *Osteoarthritis, Knee/drug therapy ; *Anti-Inflammatory Agents, Non-Steroidal/adverse effects/therapeutic use ; China ; Drugs, Chinese Herbal/adverse effects/therapeutic use ; Prospective Studies ; Treatment Outcome ; Multicenter Studies as Topic ; }, } @article {pmid39137917, year = {2024}, author = {Ribeiro Júnior, HL}, title = {Molecular monitoring of myelodysplastic neoplasm: Don't just watch this space, consider the patient's ancestry.}, journal = {British journal of haematology}, volume = {205}, number = {3}, pages = {759-760}, doi = {10.1111/bjh.19689}, pmid = {39137917}, issn = {1365-2141}, support = {UNI-0210-00007.01.00/23//Fundação Cearense de Apoio ao Desenvolvimento Científico e Tecnológico/ ; 305659/2023//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; }, mesh = {Humans ; *Myelodysplastic Syndromes/genetics/diagnosis ; Prognosis ; Mutation ; Biomarkers, Tumor/genetics ; }, abstract = {The heterogeneity of Myelodysplastic Neoplasm (MDS) extends beyond mutational diversity to include significant ethnic variability, a factor that has been underexplored. While the development of the IPSS-M prognostic tool has advanced our understanding of MDS, its reliance on data primarily from European cohorts limits its applicability to non-European populations. Duployez et al.'s review highlighted the importance of molecular markers in MDS for personalized treatment and disease monitoring yet did not address the impact of genetic ancestry. This commentary critiques the IPSS-M's limited sample of 110 Brazilian patients, questioning its adequacy in reflecting the influence of patient ancestry on prognostic accuracy. Given the potential for differing mutation profiles and prognostic implications across diverse ethnic groups, robust genomic ancestry studies are urgently needed. These studies should stratify MDS patients by ethnic background to investigate mutation incidence and impacts, thereby validating IPSS-M and potentially identifying new prognostic markers. Incorporating ethnic diversity into prognostic models is essential for ensuring they are truly universal and inclusive, thereby improving personalized treatment and care for all MDS patients. Commentary on: Duployez and Preudhomme. Monitoring molecular changes in the management of myelodysplastic syndromes. Br J Haematol 2024; 205:772-779.}, } @article {pmid39135068, year = {2024}, author = {Khanian, A and Homayuni, A and Jamshidian, Z and Salehi, A}, title = {Investigating the correlation between organizational ethics and professional ethics with job burnout and organizational commitment: a cross-sectional study in the nursing staff.}, journal = {BMC nursing}, volume = {23}, number = {1}, pages = {560}, pmid = {39135068}, issn = {1472-6955}, abstract = {BACKGROUND: Adherence to ethical principles and standards in all health professions, especially in the nursing, can have positive outcomes. This study was conducted with the aim of investigating the correlation between organizational ethics and professional ethics with organizational commitment and job burnout in nursing staff.

METHODS: This cross-sectional study was conducted on the nurses working in Shahid Montazeri hospital in Najafabad city. Participants were selected by census method. An online questionnaire was used to collect the data, which consisted of demographic information, Hunt et al.'s organizational ethics questionnaire, Petty's professional ethics inventory, Maslach and Jackson's job burnout questionnaire and Allen and Mayer's organizational commitment questionnaire. Data were analyzed using t-test, one-way analysis of variance, Pearson correlation coefficient and structural equation modeling (SEM) with SPSS-27 and Amos-23 statistical software.

RESULTS: A total of 197 subjects with the mean age of 34.67 ± 7.74 years participated in this study. Most of the participants were female (89.3%) and married (77.2%). The majority of them had a bachelor's degree (86.3%) and 61.4% of the participants participated as a nurse. There were significant positive correlations between organizational ethics (r = 0.551, p < 0.01) and professional ethics (r = 0.44, p < 0.01) with organizational commitment. Also, there were significant negative correlations between organizational ethics (r=-0.532, p < 0.01) and professional ethics (r=-0.602, p < 0.01) with job burnout.

CONCLUSION: Considering the importance of compliance with ethics in the workplace by nursing staff and its consequences such as increasing organizational commitment and reducing job burnout, it is suggested that hospital managers emphasize the compliance with ethics in the workplace as a model. They can also familiarize nursing staff with the principles and basics of organizational and professional ethics by holding training courses.}, } @article {pmid39116413, year = {2024}, author = {Fonollosa, A and Agarwal, A}, title = {Author Reply to Letter to the Editor: In Response to: Comment on Fonollosa et al.'s "Hyper-Reflective Outer Nuclear Layer (HONL) in Vogt-Koyanagi-Harada Disease and Sympathetic Ophthalmia".}, journal = {Ocular immunology and inflammation}, volume = {32}, number = {10}, pages = {2620-2621}, doi = {10.1080/09273948.2024.2389462}, pmid = {39116413}, issn = {1744-5078}, mesh = {*Uveomeningoencephalitic Syndrome/diagnosis/physiopathology/drug therapy/complications ; Humans ; *Ophthalmia, Sympathetic/diagnosis/physiopathology/drug therapy ; *Tomography, Optical Coherence ; *Visual Acuity/physiology ; }, abstract = {We have recently described an OCT sign in two patients (one with Vogt-Koyanagi-Harada (VKH) and the other with Sympathetic Ophthalmia) consisting of hyperreflectivity of the outer nuclear layer (HONL) that subsequently evolved into outer retina atrophy and associated with poor functional outcomes. Ali et al. have published a comment on our letter regarding HONL. They have evaluated it in 90 eyes of VKH patients. It was observed in 37 eyes (41.1%) and no associations were found between HONL and structural outcomes or final visual acuity, and no cases of retinal atrophy were described. In the present author's reply, we point out two reasons for these contradictory observations. First, we considered HONL a full thickness hyperreflectivity of the outer nuclear layer, whereas they included cases with partial thickness hyperreflectivity, hence probably milder cases. Second: they have assessed visual function by means of visual acuity, so cases with extrafoveal involvement whose functional deficiency might only be measured by other tests (i.e. visual field) might have been missed.}, } @article {pmid39115328, year = {2025}, author = {Xie, J and Li, R and Hong, Y}, title = {Comment on Dheyab AM. et al.'s "Long-Term Efficacy of Oral Valganciclovir in Presumed Cytomegalovirus Unilateral Hypertensive Anterior Uveitis".}, journal = {Ocular immunology and inflammation}, volume = {33}, number = {2}, pages = {324-325}, doi = {10.1080/09273948.2024.2386628}, pmid = {39115328}, issn = {1744-5078}, mesh = {Humans ; *Uveitis, Anterior/drug therapy/virology/diagnosis ; *Valganciclovir ; *Antiviral Agents/administration & dosage/therapeutic use ; *Cytomegalovirus Infections/drug therapy/diagnosis/virology ; *Eye Infections, Viral/drug therapy/virology/diagnosis ; Administration, Oral ; Cytomegalovirus ; Treatment Outcome ; }, abstract = {The inclusion criteria of patients in this study were inconsistent especially in distinguishing Fuchs' uveitis and herpetic uveitis from Posner-Schlossman syndrome, indicating well-defined inclusion criteria were needed. CMV anterior uveitis and Posner-Schlossman syndrome may not be the same disease, CMV may only act as a triggering factor for Posner-Schlossman syndrome, and the clinical manifestations of mild anterior segment inflammation were mainly caused by inflammatory reactions mediated by autoimmune factors. Although the antiviral medication was important in the treatment of Posner-Schlossman syndrome, the role of other treatment methods especially topical steroids should not be ignored.}, } @article {pmid39115030, year = {2025}, author = {Mancuso, M and Valentini, I and Basile, M and Bowen, A and Fordell, H and Laurita, R and Möller, MC and Williams, LJ and Zoccolotti, P}, title = {Cost-effectiveness of neuropsychological rehabilitation for acquired brain injuries: Update of Stolwyk et al.'s (2019) review.}, journal = {Journal of neuropsychology}, volume = {19}, number = {1}, pages = {115-139}, pmid = {39115030}, issn = {1748-6653}, mesh = {Humans ; *Cost-Benefit Analysis ; *Brain Injuries/rehabilitation/economics/complications ; *Neurological Rehabilitation/economics ; *Stroke Rehabilitation/economics ; }, abstract = {Acquired brain injuries (ABI), resulting from stroke or traumatic brain injury, cause a range of neuropsychological impairments and many patients continue to experience neuropsychological deficits years after onset. The increasing average age of the population highlights the importance of effective management strategies for the consequences of ABI. Despite the well-documented impact of rehabilitation interventions, the cost-effectiveness of neuropsychological rehabilitation remains largely unknown. This study conducted a scoping review to update the findings of Stolwyk et al. (Neuropsychological Rehabilitation, 2021, 31, 316), focusing on the economic evaluations of neuropsychological rehabilitation for individuals with ABI. Following the PIO framework, PRISMA ScR guidelines, and systematic review reporting checklist, the review screened 1027 articles and included eight studies published between 2019 and 2024. The studies encompassed either language rehabilitation or general neuropsychological programs, including neuropsychological interventions. The economic analyses, including two cost-effectiveness, five cost-utility, and one cost-benefit study, mostly adhered to CHEERS guidelines, enhancing the transparency and methodological rigour of their reporting. These studies demonstrated varying degrees of cost-effectiveness for interventions targeting post-stroke language disorders and neuropsychological rehabilitation for ABI, with significant cost savings and health benefits observed, particularly for home-based rehabilitation interventions. The included studies suffered from a short time horizon, limiting the ability to capture the long-term economic impacts and effectiveness of the interventions. Future research should focus on longer-term follow-up data and include broader search strategies to enhance understanding and optimise health care interventions. A comprehensive implementation of these economic analyses is crucial for informing policymakers, enabling them to introduce rehabilitative interventions based on solid evidence.}, } @article {pmid39113059, year = {2024}, author = {Sawyer, ADM and van Lenthe, F and Kamphuis, C and Bengoechea, EG and Luszczynska, A and Terragni, L and Volf, K and Roos, G and Woods, C and Forberger, S and Scheidmeir, M and Langøien, LJ and Neumann-Podczaska, A and Wieczorowska-Tobis, K and Stronks, K}, title = {Hypothetical mechanisms driving physical activity levels in ethnic minority groups living in Europe: a systematically identified evidence-based conceptual systems model.}, journal = {The international journal of behavioral nutrition and physical activity}, volume = {21}, number = {1}, pages = {87}, pmid = {39113059}, issn = {1479-5868}, mesh = {Humans ; *Exercise/psychology ; Europe ; *Minority Groups ; *Ethnicity ; Models, Theoretical ; }, abstract = {BACKGROUND: In Europe, physical activity levels tend to be lower in ethnic minority groups than the general population. Interventions and policies based on research examining isolated determinants of physical activity have had limited success in increasing physical activity levels. This study used systems dynamics theory and the capability approach theoretical framework to develop a conceptual model of how individual characteristics, institutional and physical environments and the migration context may interact to promote or hinder physical activity in ethnic minority groups living in Europe.

METHODS: A systematic update of Langøien et al.'s 2017 review of the determinants of physical activity in ethnic minority groups living in Europe was conducted. Our target population included individuals of all ages who reported a familial migration background from any low- and middle-income countries or belonging to minority indigenous population in Europe. Outcomes pertaining to non-work related physical activity of light, moderate or vigorous intensity performed in any setting were included. Included studies provided an evidence base from which to derive the causal loop diagrams comprising our conceptual model. Sub-system causal loop diagrams were interpreted in co-author review sessions to explicate non-linear system mechanisms, such as reinforcing and balancing feedback loops.

RESULTS: Forty-one studies were identified, of which the majority was qualitative. The conceptual model consisted of 4 causal loop diagrams relating to psychosocial constructs; sociocultural constructs; health and health communication and social and material resources, in interaction with environmental/migration context. Four hypothetical mechanisms were identified, e.g. hypothesizing that participation in organised activities leads to increased self-efficacy, thereby enabling further participation.

CONCLUSIONS: This study contributes an evidence-based conceptual systems model which elucidates how low levels of physical activity in ethnic minority groups in Europe could be supported by reinforcing and balancing mechanisms involving factors relating to physical and institutional environments, migration context and individuals. A pluralistic approach to literature review, integrating complexity methods such as CLDs into more conventional systematic literature review, supports novel insights into how factors could interact to support persistently low levels of activity, moving beyond the identification of potential relationships between isolated factors to indicating the ways in which these relationships are sustained and could be modified by intervention or policy.}, } @article {pmid39103301, year = {2024}, author = {Ghanima, W and Cooper, N}, title = {Could machine learning revolutionize how we treat immune thrombocytopenia?.}, journal = {British journal of haematology}, volume = {205}, number = {3}, pages = {770-771}, doi = {10.1111/bjh.19684}, pmid = {39103301}, issn = {1365-2141}, mesh = {Humans ; *Machine Learning ; *Purpura, Thrombocytopenic, Idiopathic/drug therapy/therapy/diagnosis ; Rituximab/therapeutic use ; Receptors, Thrombopoietin/agonists ; Adrenal Cortex Hormones/therapeutic use ; }, abstract = {The absence of reliable biomarkers in immune thrombocytopenia (ITP) complicates treatment choice, necessitating a trial-and-error approach. Machine learning (ML) holds promise for transforming ITP treatment by analysing complex data to identify predictive factors, as demonstrated by Xu et al.'s study which developed ML-based models to predict responses to corticosteroids, rituximab and thrombopoietin receptor agonists. However, these models require external validation before can be adopted in clinical practice. Commentary on: Xu et al. A novel scoring model for predicting efficacy and guiding individualised treatment in immune thrombocytopenia. Br J Haematol 2024; 205:1108-1120.}, } @article {pmid39101893, year = {2024}, author = {Brimbal, L and Roche, SP and Martaindale, MH}, title = {Interviewing and interrogation practices and beliefs, 20 years later: A national self-report survey of American police.}, journal = {Law and human behavior}, volume = {48}, number = {4}, pages = {247-261}, doi = {10.1037/lhb0000570}, pmid = {39101893}, issn = {1573-661X}, mesh = {Humans ; *Police ; United States ; Male ; *Interviews as Topic ; Female ; Adult ; *Self Report ; Middle Aged ; Surveys and Questionnaires ; Law Enforcement/methods ; Truth Disclosure ; }, abstract = {OBJECTIVE: This survey examined current law enforcement beliefs and practices about interviewing and interrogation to gauge whether they have evolved given the research and training developed over the past 20 years.

HYPOTHESES: We hypothesized that police beliefs and practices would have evolved along with research findings over the past 20 years.

METHOD: We surveyed 526 law enforcement officers about the practices and beliefs regarding interviewing and interrogation. We asked questions about officers' beliefs about rates of true and false confessions, time spent in the interrogation room, beliefs about their ability to detect deception, training experience, practices of recording interrogations, and their self-reported use of interrogation techniques.

RESULTS: Overall, when we compared our survey with Kassin et al.'s (2007) seminal survey, we found both similar results and evolving positive trends. The average interview was reportedly 1.6 hr, virtually no different from that in Kassin and colleagues' study. In addition, our sample reported that 26.2% of innocent suspects at least partially falsely confessed. Further, whereas Kassin and colleagues found that fewer than one in 10 interrogations were video recorded, we found that now more than half of interrogations are recorded in this way.

CONCLUSIONS: In a geographically diverse sample of U.S. law enforcement officers, we found significant positive trends toward knowledge and practices informed by research generated over the past decades on interviewing and interrogation. Although causality could not be determined, these findings indicate an evolution of the U.S. law enforcement mindset in a more science-based direction. (PsycInfo Database Record (c) 2024 APA, all rights reserved).}, } @article {pmid39100659, year = {2024}, author = {Eady, K and Giroux, C and Heath, S and Moreau, KA}, title = {An Innovative Course on Involving Patients in Health Professions Education.}, journal = {Perspectives on medical education}, volume = {13}, number = {1}, pages = {417-422}, pmid = {39100659}, issn = {2212-277X}, mesh = {Humans ; *Health Occupations/education ; *Patient Participation/methods/psychology ; Surveys and Questionnaires ; Curriculum/trends/standards ; Canada ; }, abstract = {Patients can be actively involved in various aspects of health professions education (HPE). However, learners in HPE graduate programs have minimal opportunities to learn how to involve patients in HPE.

We designed, implemented, and evaluated a 12-week asynchronous, online graduate course that provides learners such opportunities. We established an advisory committee of patients, clinician-educators, and professors to guide course development. Using Thomas et al.'s framework, we established the general and targeted need for the course, identified the learning outcomes, determined the learning activities, and implemented and evaluated the course. It is offered within the asynchronous, online Diploma and Master in HPE at the University of Ottawa, Canada.

EVALUATION OF INNOVATION: Forty learners participated in the course between 2020 and 2022. Using a survey with closed- and open-ended items, learners reported satisfaction with all course components, and they valued the patient narrative videos created for the course. After course completion, learners reported that the course is relevant to their professional practice. They also reported confidence in their abilities to actively involve patients in HPE. Based on the culminating assignment assessment data, learners attained course expectations.

CRITICAL REFLECTION: Although patients who participated in the narrative videos represented diverse age ranges, health conditions, and experiences in HPE, they were often Caucasian, educated, and from a higher socio-economic background. Also, the level of engagement between patients and learners in the course was limited. We are committed to improving our own patient involvement efforts.}, } @article {pmid39098257, year = {2024}, author = {Kacem, H and Poonlaphdecha, S and Ribas, A and Maceda, A and Miquel, J}, title = {Sperm characteristics of the Telorchiidae (Digenea, Plagiorchioidea): First ultrastructural data on Telorchis attenuatus an intestinal parasite of Trachemys scripta elegans.}, journal = {Tissue & cell}, volume = {90}, number = {}, pages = {102513}, doi = {10.1016/j.tice.2024.102513}, pmid = {39098257}, issn = {1532-3072}, mesh = {Animals ; Male ; *Turtles/parasitology ; *Spermatozoa/ultrastructure ; *Trematoda/ultrastructure ; Microscopy, Electron, Transmission ; Microtubules/ultrastructure ; Axoneme/ultrastructure ; Mitochondria/ultrastructure ; Intestines/parasitology/ultrastructure ; }, abstract = {The ultrastructural features of the mature spermatozoon of Telorchis attenuatus (Digenea, Telorchiidae), an intestinal parasite of the red-eared turtle Trachemys scripta elegans (Testudines, Emydidae), are described using transmission electron microscopy (TEM). The mature spermatozoon of T. attenuatus is a filiform cell tapered at both ends and displays Bakhoum et al.'s type IV of digenean sperm cells. Spermatozoa of T. attenuatus have: (i) two axonemes of different lengths with the 9+'1' pattern of trepaxonematan Platyhelminthes, surrounded by a continuous submembranous layer of cortical microtubules at their anterior end, (ii) an external ornamentation of the plasma membrane following Quilichini et al.'s type 2 and associated with cortical microtubules, (iii) two bundles of parallel cortical microtubules with the maximum number situated in the anterior part of the sperm cell, (iv) spine-like bodies, (v) two mitochondria, and (vi) a large number of irregularly distributed glycogen granules. Furthermore, the morphology of the posterior spermatozoon extremity in T. attenuatus corresponds to the Quilichini et al.'s fasciolidean type. The results of the current study are especially compared to the existing information from other families within the superfamily Plagiorchioidea.}, } @article {pmid39095710, year = {2024}, author = {Li, A and Zhou, H and Xiong, S and Li, J and Mallik, S and Fei, R and Liu, Y and Zhou, H and Wang, X and Hei, X and Wang, L}, title = {PLEKv2: predicting lncRNAs and mRNAs based on intrinsic sequence features and the coding-net model.}, journal = {BMC genomics}, volume = {25}, number = {1}, pages = {756}, pmid = {39095710}, issn = {1471-2164}, support = {2024JC-YBMS-484//Natural Science Basic Research Program of Shaanxi Province/ ; 61971347//the National Natural Science Foundation of China/ ; 62202374//the National Natural Science Foundation of China/ ; U21A20524//the National Natural Science Foundation of China/ ; 62176146//the National Natural Science Foundation of China/ ; 62120106011//the National Natural Science Foundation International cooperation and exchange projects/ ; }, mesh = {*RNA, Long Noncoding/genetics ; *RNA, Messenger/genetics ; Humans ; Animals ; Software ; Computational Biology/methods ; }, abstract = {BACKGROUND: Long non-coding RNAs (lncRNAs) are RNA transcripts of more than 200 nucleotides that do not encode canonical proteins. Their biological structure is similar to messenger RNAs (mRNAs). To distinguish between lncRNA and mRNA transcripts quickly and accurately, we upgraded the PLEK alignment-free tool to its next version, PLEKv2, and constructed models tailored for both animals and plants.

RESULTS: PLEKv2 can achieve 98.7% prediction accuracy for human datasets. Compared with classical tools and deep learning-based models, this is 8.1%, 3.7%, 16.6%, 1.4%, 4.9%, and 48.9% higher than CPC2, CNCI, Wen et al.'s CNN, LncADeep, PLEK, and NcResNet, respectively. The accuracy of PLEKv2 was > 90% for cross-species prediction. PLEKv2 is more effective and robust than CPC2, CNCI, LncADeep, PLEK, and NcResNet for primate datasets (including chimpanzees, macaques, and gorillas). Moreover, PLEKv2 is not only suitable for non-human primates that are closely related to humans, but can also predict the coding ability of RNA sequences in plants such as Arabidopsis.

CONCLUSIONS: The experimental results illustrate that the model constructed by PLEKv2 can distinguish lncRNAs and mRNAs better than PLEK. The PLEKv2 software is freely available at https://sourceforge.net/projects/plek2/ .}, } @article {pmid39093076, year = {2024}, author = {Oriá, RB and Smith, CJ and Ashford, JW and Vitek, MP and Guerrant, RL}, title = {Pros and Cons of APOE4 Homozygosity and Effects on Neuroplasticity, Malnutrition, and Infections in Early Life Adversity, Alzheimer's Disease, and Alzheimer's Prevention.}, journal = {Journal of Alzheimer's disease : JAD}, volume = {100}, number = {s1}, pages = {S179-S185}, doi = {10.3233/JAD-240888}, pmid = {39093076}, issn = {1875-8908}, mesh = {Humans ; *Alzheimer Disease/genetics/prevention & control ; *Apolipoprotein E4/genetics ; *Neuronal Plasticity/genetics ; *Malnutrition/genetics/complications ; Homozygote ; Life Style ; }, abstract = {Fortea et al.'s. (2024) recent data analysis elegantly calls attention to familial late-onset Alzheimer's disease (AD) with APOE4 homozygosity. The article by Grant (2024) reviews the factors associated with AD, particularly the APOE genotype and lifestyle, and the broad implications for prevention, both for individuals with the lifestyles associated with living in resource-rich countries and for those enduring environmental adversity in poverty settings, including high exposure to enteric pathogens and precarious access to healthcare. Grant discusses the issue of APOE genotype and its implications for the benefits of lifestyle modifications. This review highlights that bearing APOE4 could constitute an evolutionary benefit in coping with heavy enteric infections and malnutrition early in life in the critical formative first two years of brain development. However, the critical issue may be that this genotype could be a health concern under shifts in lifestyle and unhealthy diets during aging, leading to severe cognitive impairments and increased risk of AD. This commentary supports the discussions of Grant and the benefits of improving lifestyle for decreasing the risks for AD while providing further understanding and modelling of the early life benefits of APOE4 amidst adversity. This attention to the pathophysiology of AD should help further elucidate these critical, newly appreciated pathogenic pathways for developing approaches to the prevention and management in the context of the APOE genetic variations associated with AD.}, } @article {pmid39086823, year = {2024}, author = {Wu, R and Lim, JT and Ahmed, Z and Berger, R and Acem, E and Chowdhury, I and White, SJ}, title = {Do autistic adults spontaneously reason about belief? A detailed exploration of alternative explanations.}, journal = {Royal Society open science}, volume = {11}, number = {7}, pages = {231889}, pmid = {39086823}, issn = {2054-5703}, abstract = {Southgate et al.'s (Southgate 2007 Psychol. Sci. 18, 587-92 (doi:10.1111/j.1467-9280.2007.01944.x)) anticipatory-looking paradigm has presented exciting yet inconclusive evidence surrounding spontaneous mentalizing in autism. The present study aimed to develop this paradigm to address alternative explanations for the lack of predictive eye movements on false-belief tasks by autistic adults. This was achieved through implementing a multi-trial design with matched true-belief conditions, and both high and low inhibitory demand false-belief conditions. We also sought to inspect if any group differences were related to group-specific patterns of attention on key events. Autistic adults were compared with non-autistic adults on this adapted implicit mentalizing task and an established explicit task. The two groups performed equally well in the explicit task; however, autistic adults did not show anticipatory-looking behaviour in the false-belief trials of the implicit task. Critically, both groups showed the same attentional distribution in the implicit task prior to action prediction, indicating that autistic adults process information from social cues in the same way as non-autistic adults, but this information is not then used to update mental representations. Our findings further document that many autistic people struggle to spontaneously mentalize others' beliefs, and this non-verbal paradigm holds promise for use with a wide range of ages and abilities.}, } @article {pmid39081613, year = {2024}, author = {Wong, J and Hung, L and Bayabay, C and Wong, KLY and Berndt, A and Mann, J and Wong, L and Jackson, L and Gregorio, M}, title = {A critical reflection on using the Patient Engagement In Research Scale (PEIRS) to evaluate patient and family partners' engagement in dementia research.}, journal = {Frontiers in dementia}, volume = {3}, number = {}, pages = {1422820}, pmid = {39081613}, issn = {2813-3919}, abstract = {INTRODUCTION: Research involvement of people with lived experiences is increasing. Few tools are designed to evaluate their engagement in research. The Patient Engagement In Research Scale (PEIRS) is one of the few validated tools. Our team employed the PEIRS with patient and family partners with lived experiences of dementia every 6 months in a two-year telepresence robot project. This reflection paper reports our self-study on key learnings and proposes practical tips on using the PEIRS to evaluate patient and family partners' engagement in dementia research. It is the first to document a case using the PEIRS multiple times in a dementia research project.

METHODS: Guided by Rolfe et al.'s reflective model, we conducted three team reflective sessions to examine the team's experiences using the PEIRS to improve and evaluate patient and family partners' engagement in the research. We also reviewed our meeting notes and fieldnotes documented in the research journal. A reflexive thematic analysis was performed.

RESULTS: The team identified three key learnings: the values of using the PEIRS survey, the adaptations, and the factors influencing its implementation as an evaluation tool. Using the PEIRS provided significant benefits to the project, although some patient and family partners felt it was burdensome. The evaluation tool was enhanced with emojis and comment boxes based on suggestions from patient partners. The emojis introduced an element of fun, while the comment boxes allowed for personalized responses. Several factors influenced the PEIRS tool's effectiveness: the interviewer's identity, the confidentiality of responses and follow-ups, the timing and frequency of using the tool, and the presentation of the evaluations. These learnings led to the development of six practical tips,-"ENGAGE": Enjoyable and fun process, Never impose, Get prepared early, Adapt to the team's needs, Give people options, and Engage and reflect.

CONCLUSION: With the emerging trend of including people with lived experiences in dementia research, there is a need for ongoing assessment of engagement from both patient and family partners and the research team strategies. Future research can further explore survey logistics, co-development of evaluation tools, and the use of tools with people living with dementia.}, } @article {pmid39079101, year = {2024}, author = {Watkins, NW and Calel, R and Chapman, SC and Chechkin, A and Klages, R and Stainforth, DA}, title = {The challenge of non-Markovian energy balance models in climate.}, journal = {Chaos (Woodbury, N.Y.)}, volume = {34}, number = {7}, pages = {}, doi = {10.1063/5.0187815}, pmid = {39079101}, issn = {1089-7682}, abstract = {We first review the way in which Hasselmann's paradigm, introduced in 1976 and recently honored with the Nobel Prize, can, like many key innovations in complexity science, be understood on several different levels. It can be seen as a way to add variability into the pioneering energy balance models (EBMs) of Budyko and Sellers. On a more abstract level, however, it used the original stochastic mathematical model of Brownian motion to provide a conceptual superstructure to link slow climate variability to fast weather fluctuations, in a context broader than EBMs, and led Hasselmann to posit a need for negative feedback in climate modeling. Hasselmann's paradigm has still much to offer us, but naturally, since the 1970s, a number of newer developments have built on his pioneering ideas. One important one has been the development of a rigorous mathematical hierarchy that embeds Hasselmann-type models in the more comprehensive Mori-Zwanzig generalized Langevin equation (GLE) framework. Another has been the interest in stochastic EBMs with a memory that has slower decay and, thus, longer range than the exponential form seen in his EBMs. In this paper, we argue that the Mori-Kubo overdamped GLE, as widely used in statistical mechanics, suggests the form of a relatively simple stochastic EBM with memory for the global temperature anomaly. We also explore how this EBM relates to Lovejoy et al.'s fractional energy balance equation.}, } @article {pmid39073213, year = {2024}, author = {Brown, T and Fagerlin, A and Samore, MH and Harris, AHS and Galyean, P and Zickmund, S and Pettey, WBP and Vanneman, ME}, title = {Information and resources VA health system leaders need to manage enrollment and retention for Post-9/11 veterans.}, journal = {Health services research}, volume = {59}, number = {5}, pages = {e14351}, pmid = {39073213}, issn = {1475-6773}, support = {RCS 14-232/HX/HSRD VA/United States ; CDA15-259//VA Health Services Research and Development (HSR&D) Career Development Award/ ; UM1 TR004409/TR/NCATS NIH HHS/United States ; CIN13-414//VA Health Services Research and Development (HSR&D) Career Development Award/ ; IK2 HX002625/HX/HSRD VA/United States ; 1IK2HX002625-01A1//VA Health Services Research and Development (HSR&D) Career Development Award/ ; CIN 13-414//Informatics, Decision-Enhancement and Analytic Sciences (IDEAS) Center of Innovation/ ; }, mesh = {Humans ; United States ; *United States Department of Veterans Affairs/organization & administration ; *Veterans/psychology ; Leadership ; September 11 Terrorist Attacks ; Interviews as Topic ; Qualitative Research ; Male ; Female ; }, abstract = {OBJECTIVE: To understand Veterans Health Administration (VA) leaders' information and resource needs for managing post-9/11 Veterans' VA enrollment and retention.

Interviews conducted from March-May 2022 of VA Medical Center (VAMC) leaders (N = 27) across 15 sites, using stratified sampling based on VAMC characteristics: enrollment rates, number of recently separated Veterans in catchment area, and state Medicaid expansion status.

STUDY DESIGN: Interview questions were developed using Petersen et al.'s Factors Influencing Choice of Healthcare System framework as a guide. Interviews were transcribed verbatim, and two coders analyzed the interviews using Atlas.ti, a qualitative software program. Coders followed the qualitative coding philosophy developed by Crabtree and Miller, a process of developing codes for salient concepts as they are identified during the analysis process.

Two coders analyzed 22% (N = 6) of the interviews and discussed and adjudicated any discrepancies. One coder independently coded the remainder of the interviews.

PRINCIPAL FINDINGS: Several key themes were identified regarding facilitators and barriers for VA enrollment including reputation for high-quality VA care, convenience of VA services, awareness of VA services and benefits, and VA mental health services. Nearly every VA leader actively used tools and data to understand enrollment and retention rates and sought to enroll and retain more Veterans. To improve the management of enrollment and retention, VA leaders would like data shared in an easily understandable format and the capability to share data between the VA and community healthcare systems.

CONCLUSIONS: Enrollment and retention information is important for healthcare leaders to guide their health system decisions. Various tools are currently being used to try to understand the data. However, a multifunctional tool is needed to better aggregate the data to provide VA leadership with key information on Veterans' enrollment and retention.}, } @article {pmid39070890, year = {2024}, author = {Nordmann, K and Sauter, S and Redlich, MC and Möbius-Lerch, P and Schaller, M and Fischer, F}, title = {Challenges and conditions for successfully implementing and adopting the telematics infrastructure in German outpatient healthcare: A qualitative study applying the NASSS framework.}, journal = {Digital health}, volume = {10}, number = {}, pages = {20552076241259855}, pmid = {39070890}, issn = {2055-2076}, abstract = {BACKGROUND: Germany's healthcare system provides high-quality, universal health coverage to almost all residents. However, a major challenge lies in the strong separation of healthcare structures, which hinders efficient interprofessional and intersectoral communication and collaboration. The mandatory nationwide implementation of the telematics infrastructure may offer a solution to enhance healthcare professionals' communication and collaboration.

OBJECTIVE: Our study aims to elicit participants' perceptions of and attitudes towards the implementation and usage of the telematics infrastructure in fostering interprofessional communication and collaboration between home-care nursing services and general practitioner practices.

METHODS: We conducted interviews with seven members of general practitioner practices and 10 in home-care nursing services. Using thematic content analysis, we identified five themes, of which four along with 10 subthemes were integrated into Greenhalgh et al.'s 'nonadoption, abandonment, scale-up, spread and sustainability' framework.

RESULTS: Participants recognised the potential of digital technology to enhance interprofessional communication and collaboration. However, this potential largely depended on individual healthcare actors' willingness to seek information, invest and adapt. Attitudes towards the telematics infrastructure varied widely from hopeful confidence to outright rejection. Home-care nursing services generally viewed the telematics infrastructure with optimism, while general practitioners expressed reservations, particularly due to technological disruptions, lack of user-friendliness, and organisational structures.

CONCLUSION: Our findings highlight the potential of digital technology to enhance interprofessional communication. Successful implementation of technological innovations, however, goes beyond technological aspects and involves social, political and organisational processes. Future implementation strategies for such innovations in healthcare should involve users early and ensure clear communication.}, } @article {pmid39070556, year = {2024}, author = {Wu, D and Xia, X}, title = {Frontiers in premature beats research: a bibliometric analysis.}, journal = {Frontiers in cardiovascular medicine}, volume = {11}, number = {}, pages = {1343274}, pmid = {39070556}, issn = {2297-055X}, abstract = {BACKGROUND: This study aimed to assess the scientific results and activities of premature beats research from a global perspective.

METHODS: Publications related to premature beats published between 2003 and 2024 were identified and selected from the Web of Science core collection. VOSviewer was used to conduct co-authorship, co-citation, and co-occurrence analyses of the authors, organizations, countries/regions, references, sources, cited authors, and keywords.

RESULTS: In total, 5,283 publications on the topic of premature beats were identified from the Web of Science core collection. The number of publications on this topic has steadily grown since 2003. Fred Morady, Frank Bogun and Krit Jongnarangsin were the top three researchers with the strongest total link strengths. The University of Washington, Johns Hopkins University, and the University of Minnesota are the top three organizations with the strongest total link strengths. The United States has made the greatest contributions to the field of premature beats. Haïssaguerre, M et al.'s publication in The New England Journal of Medicine in 1998 entitled "Spontaneous initiation of atrial fibrillation by ectopic beats originating in the pulmonary veins" is the most cited reference. The most cited references come from the journal named Circulation. Haïssaguerre, M has the highest number of citations. The keywords for all current publications can be divided into four categories: "mortality rate," "risk and prevention," "mechanism," and "classification and treatment."

CONCLUSIONS: This bibliometric study provides insights into the current status and research trends in premature beats over more than 20 years. Future research will focus on an in-depth exploration of the nature of premature beats, especially ventricular premature beats, mastering the development law of premature beats, and optimizing existing detection methods.}, } @article {pmid39063666, year = {2024}, author = {Aşır, F and Korak, T and Çankırı, Z}, title = {Reply to Abid et al. Comment on "Aşır et al. Investigation of Vitamin D Levels in Men with Suspected Infertility. Life 2024, 14, 273".}, journal = {Life (Basel, Switzerland)}, volume = {14}, number = {7}, pages = {}, pmid = {39063666}, issn = {2075-1729}, abstract = {In response to the insightful comments made by Dr. Abid et al. on our article "Investigation of Vitamin D Levels in Men with Suspected Infertility", we address several key points concerning the generalizability and methodology of our study. Dr. Abid et al.'s critique primarily focused on the single-center nature of our research, regional variations in ultraviolet (UV) exposure, dietary factors affecting vitamin D levels, and the sample size of our study. We discuss the inherent value and controlled environment of single-center studies while acknowledging the need for multi-center validation. Additionally, we explain our consideration of sun exposure and dietary intake in our analysis, and recognize the importance of larger, more diverse studies to strengthen our findings. Our response aims to clarify these aspects and emphasize the significance of vitamin D in male infertility, encouraging further research in this field.}, } @article {pmid39061054, year = {2024}, author = {Vaishya, R and Vaish, A}, title = {The influence of operation time for hip hemiarthroplasty on complication rates and mortality in patients with femoral neck fracture: a retrospective data analysis.}, journal = {Journal of orthopaedic surgery and research}, volume = {19}, number = {1}, pages = {438}, pmid = {39061054}, issn = {1749-799X}, mesh = {Humans ; *Femoral Neck Fractures/surgery/mortality ; *Hemiarthroplasty/methods/adverse effects ; Retrospective Studies ; *Postoperative Complications/epidemiology/etiology/mortality/prevention & control ; *Operative Time ; Female ; Male ; Aged ; Aged, 80 and over ; Arthroplasty, Replacement, Hip/adverse effects/methods ; }, abstract = {Ramadanov et al.'s study highlights the importance of minimizing operative time in HHA for femoral neck fractures. Future prospective studies are needed to explore causality and refine strategies for achieving shorter, yet safe, procedures.}, } @article {pmid39058668, year = {2024}, author = {Miller, MQ}, title = {Invited Commentary: Ozucer et al.'s "Tips and Tricks for Safe and Precise Decision-Making during Modified Selective Neurectomy Surgery": An Innovative Technique That Improves but Does Not Resolve Unpredictability in Neurectomy Surgery.}, journal = {Facial plastic surgery & aesthetic medicine}, volume = {}, number = {}, pages = {}, doi = {10.1089/fpsam.2024.0170}, pmid = {39058668}, issn = {2689-3622}, } @article {pmid39057588, year = {2024}, author = {Notarnicola, I and Duka, B and Lommi, M and Prendi, E and Cristofori, E and Mele, T and Ivziku, D and Rocco, G and Stievano, A}, title = {Empowering Nurse Health Education: Linguistic and Cultural Validation of the Nurse Health Education Competence Instrument (NHECI) in the Italian Context.}, journal = {Healthcare (Basel, Switzerland)}, volume = {12}, number = {14}, pages = {}, pmid = {39057588}, issn = {2227-9032}, abstract = {BACKGROUND: Nurses worldwide are acknowledged for their role in health education across various settings. However, doubts often arise regarding their competence in this domain. This study aims to validate the Nurse Health Education Competence Instrument (NHECI) linguistically and culturally in the Italian context.

METHODS: Following Beaton et al.'s (2000) guidelines, we conducted cross-cultural adaptation to develop the Italian version of the questionnaire.

RESULTS: The Italian version demonstrates a good internal consistency and stability, making it suitable for assessing nursing students during clinical internships and practicing nurses. The availability of Italian tools promotes healthcare research, ensuring patient-centric care.

CONCLUSIONS: The validity and reliability of the Italian version of the instrument for assessing health education competencies, essential for self-assessment among health education nurses, are established.}, } @article {pmid39052394, year = {2024}, author = {Tse, CS and Yap, MJ and Chan, YL}, title = {Neighborhood in Chinese lexicon: A megastudy analysis of lexical decision and naming of two-character Chinese words.}, journal = {Journal of experimental psychology. Learning, memory, and cognition}, volume = {50}, number = {9}, pages = {1489-1515}, doi = {10.1037/xlm0001357}, pmid = {39052394}, issn = {1939-1285}, support = {//Hong Kong Research Grants Council/ ; }, mesh = {Humans ; *Psycholinguistics ; *Pattern Recognition, Visual/physiology ; *Reading ; Semantics ; China ; Adult ; Decision Making/physiology ; Recognition, Psychology/physiology ; }, abstract = {The present study examines the impact of neighborhood size (number of other two-character words sharing the same character at the same position) on Chinese lexical processing, along with its joint effects with variables such as character frequency, word frequency, and semantic transparency. Previous factorial experiments have yielded conflicting results that are difficult to reconcile with existing models (Li et al., 2015, 2017). To provide high-powered tests for these theoretically important effects on visual word recognition, we leveraged the megastudy approach and used linear mixed-effect analyses to investigate lexical decision and naming responses to a large pool of two-character Chinese words (N > 17,000) sourced from Tse et al.'s (2017, 2023) database. In all analyses we controlled for extraneous orthographic (e.g., stroke count), phonological (e.g., consistency), and semantic (e.g., transparency) variables. In addition to evaluating Li et al.'s (2015, 2017) models, we also investigated whether the parallel dual-route mechanism, which entails lexical access via whole-word or character decomposition-then-composition, could account for neighborhood size effect and its interactions in lexical decision and naming. Finally, we discuss the implications of our findings on the specificity of lexical effects with regard to character position and lexical processing task. (PsycInfo Database Record (c) 2024 APA, all rights reserved).}, } @article {pmid39046885, year = {2024}, author = {Schmertmann, CP}, title = {Commentary on van Raalte et al.'s "The Dangers of Drawing Cohort Profiles From Period Data: A Research Note".}, journal = {Demography}, volume = {61}, number = {4}, pages = {967-971}, doi = {10.1215/00703370-11484875}, pmid = {39046885}, issn = {1533-7790}, mesh = {Humans ; *Algorithms ; Cohort Studies ; Birth Rate/trends ; Age Factors ; Female ; }, abstract = {van Raalte et al. (2023) alerted demographers to the potential dangers of calculating cohort measures from the "diagonals" of gridded age-period (AP) data. In the case of cohort fertility, however, a minor change to the estimation procedure can mitigate the trend and cohort size biases that the authors identify. With an appropriate algorithm, researchers can estimate cohort fertility indices from AP data quite well.}, } @article {pmid39042835, year = {2025}, author = {Yamani, Y and Long, SK and Sato, T and Braitman, AL and Politowicz, MS and Chancey, ET}, title = {Multilevel Confirmatory Factor Analysis Reveals Two Distinct Human-Automation Trust Constructs.}, journal = {Human factors}, volume = {67}, number = {2}, pages = {166-180}, doi = {10.1177/00187208241263774}, pmid = {39042835}, issn = {1547-8181}, mesh = {*Trust ; Humans ; Factor Analysis, Statistical ; *Man-Machine Systems ; Adult ; Automation ; Male ; Female ; }, abstract = {OBJECTIVE: This work examined the relationship of the constructs measured by the trust scales developed by Chancey et al. (2017) and Jian et al. (2000) using a multilevel confirmatory factor analysis (CFA).

BACKGROUND: Modern theories of automation trust have been proposed based on data collected using trust scales. Chancey et al. (2017) adapted Madsen and Gregor's (2000) trust scale to align with Lee and See's (2004) human-automation trust framework. In contrast, Jian et al. (2000) developed a scale empirically with trust and distrust as factors. However, it remains unclear whether these two scales measure the same construct.

METHOD: We analyzed data collected from previous experiments to investigate the relationship between the two trust scales using a multilevel CFA.

RESULTS: Data provided evidence that Jian et al. (2000) and Chancey et al. (2017) automation trust scales are only weakly related. Trust and distrust are found to be distinct factors in Jian et al.'s (2000) scale, whereas performance, process, and purpose are distinct factors in Chancey et al.'s (2017) trust scale.

CONCLUSION: The analysis suggested that the two scales purporting to measure human-automation trust are only weakly related.

APPLICATION: Trust researchers and automation designers may consider using Chancey et al. (2017) and Jian et al. (2000) scales to capture different characteristics of human-automation trust.}, } @article {pmid39039396, year = {2025}, author = {Gunduz, H and Ozkan Ceylan, A}, title = {Load effect of visual working memory on distractor interference: An investigation with two replication experiments.}, journal = {Memory & cognition}, volume = {53}, number = {3}, pages = {832-852}, pmid = {39039396}, issn = {1532-5946}, mesh = {Humans ; *Memory, Short-Term/physiology ; *Attention/physiology ; Young Adult ; Adult ; *Visual Perception/physiology ; Female ; Male ; *Psychomotor Performance/physiology ; }, abstract = {Konstantinou et al. (Experiment 1B; Attention, Perception, & Psychophysics, 76, 1985-1997, 2014) reported that an increase in visual short-term memory (VSTM) load reduced distractor interference in the flanker task. Yao et al. (Experiment 3; Attention, Perception, & Psychophysics, 82, 3291-3313, 2020) replicated the design of Konstantinou et al.'s experiment and showed that the VSTM load did not modulate the distractor interference effect, contradicting the original findings. However, it is unknown whether differences in task-design between the two experiments contributed to the inconsistent results. Therefore, we first replicated the original two studies with Experiment 1 (N = 54) and Experiment 2 (N = 54) and performed a statistical comparison between the data from these two experiments. In a third experiment (N = 28), we incorporated articulatory suppression into the design to exclude possible effects of verbalization. According to the ANOVA analyses, the VSTM load did not change the level of distractor interference in all three experiments, indicating that differences in task design alone do not explain the inconsistency.}, } @article {pmid39036664, year = {2023}, author = {Su, X and Wang, Z and Duan, S}, title = {Targeted drug delivery systems for pancreatic ductal adenocarcinoma: overcoming tumor microenvironment challenges with CAF-specific nanoparticles.}, journal = {Journal of the National Cancer Center}, volume = {3}, number = {4}, pages = {306-309}, pmid = {39036664}, issn = {2667-0054}, abstract = {Pancreatic ductal adenocarcinoma (PDAC) stands as a profoundly heterogeneous and aggressive malignancy, manifesting a discouragingly limited response to conventional therapeutic interventions. Within the intricate tapestry of the tumor microenvironment (TME), cancer-associated fibroblasts (CAFs) emerge as pivotal constituents, wielding the capacity to propel the malignant attributes of neoplastic cells while bolstering their deftness in thwarting treatments. The rapid evolution of nanomedicinal technologies ushers in fresh avenues for therapeutic paradigms meticulously honed to target CAFs. Notably, a recent proposition by Yuan et al. introduces a PDAC treatment strategy metaphorically akin to "shooting fish in a barrel." By adeptly capitalizing on the spatial distribution of the CAF barricade encircling the tumor, this innovative approach orchestrates a metamorphosis of CAFs, transitioning them from impediments to drug delivery into reservoirs of therapeutic agents. The resultant outcome, an augmentation of chemotherapy and immunotherapy efficacy, attests to the transformative potential of this concept. The study not only bequeaths novel insights and methodologies to surmount barriers in drug delivery for tumor treatment but also holds promise in elevating the precision, efficacy, and safety of tailored therapeutic regimens. Within this discourse, we meticulously evaluate Yuan et al.'s research, scrutinizing its merits and limitations, and cast a forward-looking gaze upon the formulation, validation of efficacy, and clinical translation of nanomedicines targeting CAFs.}, } @article {pmid39030857, year = {2024}, author = {Lazarus, L and McClarty, LM and Herpai, N and Pavlova, D and Tarasova, T and Gnatenko, A and Bondar, T and Lorway, R and Becker, ML and , }, title = {"…because the social work never ends": a qualitative study exploring how NGOs responded to emerging needs while upholding responsibility to HIV prevention and treatment during the war in Ukraine.}, journal = {Journal of the International AIDS Society}, volume = {27 Suppl 3}, number = {Suppl 3}, pages = {e26309}, pmid = {39030857}, issn = {1758-2652}, support = {PJT-148876/CAPMC/CIHR/Canada ; }, mesh = {Humans ; Ukraine/epidemiology ; *HIV Infections/prevention & control/psychology/drug therapy ; Male ; *Qualitative Research ; Female ; *Organizations ; Interviews as Topic ; Adult ; Armed Conflicts ; }, abstract = {INTRODUCTION: Since the onset of the Russian invasion on 24 February 2022, the health system in Ukraine has been placed under tremendous pressure, with damage to critical infrastructure, large losses of human resources, restricted mobility and significant supply chain interruptions. Based on a longstanding partnership between the Ukrainian Institute for Social Research after Oleksandr Yaremenko (UISR after O. Yaremenko) and the Institute for Global Public Health at the University of Manitoba, we explore the impact of the full-scale war on non-governmental organizations (NGOs, including charitable organizations) providing services for key population groups in Ukraine.

METHODS: We conducted in-depth qualitative interviews with key representatives from NGOs working with key population groups (i.e., people living with HIV, sex workers, men who have sex with men, people who inject drugs and transgender people) throughout Ukraine. Members of the UISR after O. Yaremenko research team recruited participants from organizations working at national, regional and local levels. The research team members conducted 26 interviews (22 with women and four with men) between 15 May and 7 June 2023. Interviews were conducted virtually in Ukrainian and interpretively analysed to draw out key themes.

RESULTS: Applying Roels et al.'s notion of "first responders", our findings explore how the full-scale war personally and organizationally impacted workers at Ukrainian NGOs. Despite the impacts to participants' physical and mental health, frontline workers continued to support HIV prevention and treatment while also responding to the need for humanitarian aid among their clients and the wider community. Furthermore, despite inadequate pay and compensation for their work, frontline workers assumed additional responsibilities, thereby exceeding their normal workload during the extraordinary conditions of war.

CONCLUSIONS: NGOs play a vital role as responders, adapting their services to meet the emergent needs of communities during structural shocks, such as war. There is an urgent need to support NGOs with adequate resources for key population service delivery and to increase support for their important role in humanitarian aid.}, } @article {pmid39024057, year = {2024}, author = {Jung, I and Suh, Y and Kim, MH and Roh, JH}, title = {Response to: Possible biases in Roh et al.'s article about the association between COVID-19 vaccination and Alzheimer's disease.}, journal = {QJM : monthly journal of the Association of Physicians}, volume = {117}, number = {10}, pages = {755-756}, doi = {10.1093/qjmed/hcae139}, pmid = {39024057}, issn = {1460-2393}, support = {RS-2023-00220894//National Research Foundation/ ; //Korea Dementia Research/ ; //Korea Dementia Research Center/ ; //Ministry of Health & Welfare and Ministry of Science/ ; RS-2024-00344521//ICT/ ; //Republic of Korea/ ; K2123751//Korea University/ ; }, } @article {pmid39024056, year = {2024}, author = {Cerqueira-Silva, T and Boaventura, VS and Oliveira-Filho, J and Barral-Netto, M and Pearce, N}, title = {Possible biases in Roh et al.'s article about the association between COVID-19 vaccination and Alzheimer's disease.}, journal = {QJM : monthly journal of the Association of Physicians}, volume = {117}, number = {10}, pages = {753-754}, doi = {10.1093/qjmed/hcae137}, pmid = {39024056}, issn = {1460-2393}, support = {NIF\R1\231435//Royal Society/ ; //Brazilian National Research Council research/ ; }, } @article {pmid39023845, year = {2024}, author = {Nicholson, T and Lee, R}, title = {Parental illness work across the attention deficit hyperactivity disorder diagnostic journey.}, journal = {Sociology of health & illness}, volume = {46}, number = {8}, pages = {1647-1667}, doi = {10.1111/1467-9566.13817}, pmid = {39023845}, issn = {1467-9566}, support = {//Doctoral Project at Northumbria University/ ; }, mesh = {Humans ; *Attention Deficit Disorder with Hyperactivity/diagnosis/psychology ; *Parents/psychology ; Female ; Male ; Child ; Adult ; England ; Longitudinal Studies ; Interviews as Topic ; Qualitative Research ; Adolescent ; }, abstract = {The process of referral, assessment, and diagnosis of attention deficit hyperactivity disorder (ADHD) within the UK is often protracted. Given that parents are frequently the instigators of the diagnostic process, understanding the experience of parents is important. Drawing on findings from a longitudinal study, this article explores how the parental experience of the ADHD diagnostic journey includes three significant and distinct forms of 'illness work'. Twenty-one semi-structured serial interviews were conducted over a 2-year period with seven parents of children on the ADHD diagnostic journey in North East England. We present three significant forms of parental illness work: (1) The 'diagnostic quest', parental work recognising and fighting for their children's needs and selfhood, seeking diagnosis and engaging with systems, (2) 'self-biographical illness work', the personal parental biographical response to the diagnostic journey and (3) 'child biographical illness work and recontextualizing the child', parental biographical adjustment and recontextualisation of their children. We advance Rasmussen et al.'s (2021) model by demonstrating its usefulness in understanding how parents with a personal ADHD diagnosis experience biographical disruption or cohesion in response to their children's diagnosis. That a child's diagnosis leads parents with ADHD to experience a self-biographical cohesive or disruptive response is a unique and significant finding.}, } @article {pmid39023156, year = {2024}, author = {Isaac, DM and Lefèvre, C}, title = {[Life satisfaction and emotional regulation in aging: temporal perspective and effect of gender].}, journal = {Geriatrie et psychologie neuropsychiatrie du vieillissement}, volume = {22}, number = {2}, pages = {209-216}, doi = {10.1684/pnv.2024.1174}, pmid = {39023156}, issn = {2115-7863}, mesh = {Humans ; Female ; Male ; *Personal Satisfaction ; Aged ; *Aging/psychology ; Middle Aged ; *Emotional Regulation ; Aged, 80 and over ; Surveys and Questionnaires ; Time Perception ; Sex Factors ; }, abstract = {Few studies have examined the relationship between life satisfaction, emotional regulation and perception of future time in the elderly. Thirty-one women and 28 men (age M = 70,51 ± 3,98) were questioned using the Gross and John's Emotion Regulation Questionnaire (2003), the Blais et al.'s Life Satisfaction Scale (1989) and the Castersen and Lang's Future Time Perception Scale (1996). The results show that there is no gender effect, and do not support the motivational theory of Carstensen, Isaacowitch and Charles (1999), which postulates a link between temporal perspective and the selection of the most efficient emotional regulation strategies. This research shows that it is the use of compensatory strategies that enables people to continue to be satisfied with their lives despite advancing age. Nor do these strategies influence the effect of gender or perception of future time on life satisfaction. Against a backdrop of an aging population, this study is helping to better define the features of well-being in the advancing age.}, } @article {pmid39014459, year = {2024}, author = {Cao, S and Hu, X and Tang, Y and Wu, K and Yang, W and Li, X}, title = {Weight-adjusted-waist index is positively associated with urinary incontinence: results from the National Health and Nutrition Examination Survey (NHANES) 2001-2018.}, journal = {European journal of medical research}, volume = {29}, number = {1}, pages = {368}, pmid = {39014459}, issn = {2047-783X}, support = {2022YFS0133//Sichuan Province Science and Technology Support Program/ ; }, mesh = {Humans ; Female ; *Nutrition Surveys ; Middle Aged ; Male ; Cross-Sectional Studies ; *Waist Circumference ; Adult ; *Urinary Incontinence/epidemiology/diagnosis ; *Body Mass Index ; Obesity/epidemiology ; Aged ; Body Weight ; Risk Factors ; United States/epidemiology ; }, abstract = {BACKGROUND: Urinary incontinence (UI) is closely related to obesity. The aim of this study is to evaluate the association of a novel anthropometric indicator weight-adjusted-waist index (WWI) with UI.

METHODS: This cross-sectional study used the data from National Health and Nutrition Examination Survey (NHANES) 2001-2018. Weighted multivariable logistic regression was used to evaluate the relationship between WWI and three types of UI [stress UI (SUI), urgency UI (UUI), and mixed UI (MUI)]. The receiver operating characteristic (ROC) curve and Delong et al.'s test were utilized for comparison of the predictive capability for UI between WWI and body mass index (BMI), waist circumference (WC).

RESULTS: A total of 41,614 participants were included in this study, of whom 23.57% had SUI, 19.24% had UUI, and 9.43% had MUI. In the fully adjusted model, WWI was positively associated with three types of UI [SUI: odds ratio (OR) = 1.19, 95%Confidence interval (CI) 1.13-1.25; UUI: OR = 1.18, 95%CI 1.13-1.24; MUI: OR = 1.19, 95%CI 1.11-1.27, all p < 0.001]. Compared to the lowest WWI interval, the positive correlation between WWI and UI still existed in the highest WWI group after converting WWI to a categorical variable by quartiles (SUI: OR = 1.52, 95%CI 1.35-1.71, p < 0.001; UUI: OR = 1.50, 95%CI 1.33-1.69, p < 0.001; MUI: OR = 1.55, 95%CI 1.32-1.83, p < 0.001). WWI had a stronger prediction for three types of UI than BMI and WC (all p < 0.001).

CONCLUSION: A higher WWI was linked with an increased likelihood of three types of UI (SUI, UUI, and MUI) in the United State population. Compared to BMI and WC, WWI had a stronger predictive power for UI. WWI may be a better adiposity parameter for evaluating UI.}, } @article {pmid39013662, year = {2024}, author = {Band, G and Leffler, EM}, title = {Malaria endemicity linked to shorter telomeres in leukocytes.}, journal = {Trends in parasitology}, volume = {40}, number = {8}, pages = {660-661}, pmid = {39013662}, issn = {1471-5007}, support = {R35 GM147709/GM/NIGMS NIH HHS/United States ; }, mesh = {Humans ; *Malaria/epidemiology ; *Leukocytes ; *Telomere ; Endemic Diseases ; Telomere Shortening ; Incidence ; }, abstract = {Leukocyte telomere length is a highly polygenic trait that has been associated with a complex range of lifestyle factors and disease risk. McQuillan et al.'s results comparing telomere length to malaria incidence rates suggest that infections may be another important factor, possibly through permanent shortening of telomeres in hematopoietic progenitor cells.}, } @article {pmid39012784, year = {2024}, author = {Liao, M and Zhang, K and Luo, C and Zeng, H}, title = {Al-Based MOF-Derived Amorphous/Crystalline Heterophase Cobalt Sulfides as High-Performance Supercapacitor Materials.}, journal = {Inorganic chemistry}, volume = {63}, number = {30}, pages = {14074-14085}, doi = {10.1021/acs.inorgchem.4c01881}, pmid = {39012784}, issn = {1520-510X}, abstract = {Transition metal sulfides (TMSs) are promising electrode materials due to their high theoretical specific capacitance, but sluggish charge transfer kinetics and an insufficient number of active sites hamper their applications in supercapacitors. In this work, a self-sacrificial template strategy was employed to construct Al-based MOF-derived metal sulfides with an amorphous/crystalline (a/c) heterophase, in which aluminum, nitrogen, and carbon species were evenly coordinated in the amorphous phase. The metal sulfides a/c-Co(Al)S-1 and a/c-Co(Al)S-2, originating from the CAU-1 and CoAl-MOF on NF as self-sacrificial templates, were investigated as electrode materials, respectively, in which the a/c-Co(Al)S-1 showed a more excellent electrochemical performance. Through acid etching CAU-1 using Co(NO3)2 followed by sulfuration, the a/c-Co(Al)S-1 with a unique 3D network structure was constructed, whose unique architecture expanded the interfacial contact with the electrolyte and provided vast active sites, accelerating the charge transportation and ion diffusion. Notably, the a/c-Co(Al)S-1 displayed a high specific charge of 1791.8 C g[-1] at 1 A g[-1], satisfactory cycle stability, and good rate capability. The corresponding assembled a/c-Co(Al)S-1//AC device delivered a high energy density of 77.1 Wh kg[-1] at 800 W kg[-1] and good durability (87.4% capacitance retention over 10 000 cycles).}, } @article {pmid39011456, year = {2024}, author = {He, Y and Liu, J and Wei, S and Chen, J}, title = {Super-refractory status epilepticus in a woman with Aeromonas caviae meningitis: a rare case report and review of the literature.}, journal = {Frontiers in medicine}, volume = {11}, number = {}, pages = {1410762}, pmid = {39011456}, issn = {2296-858X}, abstract = {Currently, there is a lack of knowledge regarding Aeromonas caviae meningitis. We report the first case of super-refractory status epilepticus (SRSE) in a woman with Aeromonas caviae meningitis. The case report demonstrates that this condition can lead to severe SRSE. Effective treatment for epilepsy is crucial for improving the prognosis for similar patients. According to Gomes et al.'s consensus protocol for SRSE, using a combination of up to one anesthetic drug and three non-anesthetic anti-epileptic drugs may be helpful and important in managing SRSE that is caused by Aeromonas caviae meningitis.}, } @article {pmid39011173, year = {2024}, author = {Cakan, KN}, title = {Comparison of the Cameriere's third molar maturity index and Olze et al.'s stages of radiographic visibility of the root pulp in a Turkish population.}, journal = {European oral research}, volume = {58}, number = {2}, pages = {88-94}, pmid = {39011173}, issn = {2651-2823}, abstract = {PURPOSE: The purpose of this study was to compare the Cameriere's third molar maturity index and Olze et al.'s stages of radiographic visibility of the root pulp in estimating the age of maturity in the Turkish population. The age of majority, which is legally significant, marks the transition from childhood to adulthood. In Turkey, the age of majority is set at 18 years. As the third molars continue to develop at this age, they can serve as an indicator of dental age.

MATERIALS AND METHODS: A total of 705 panoramic radiographs obtained from individuals aged 15 to 22 years, including children and adults, were included in this study. The left mandibular third molars were evaluated on panoramic radiographs using Cameriere's third molar maturity index and Olze's method of radiographic root pulp visibility (RPV) stages. Minimum and maximum values were noted for each stage, and a median with upper and lower quartiles, as well as mean and standard deviation were calculated. Sensitivity and specificity values were calculated.

RESULTS: In males, Cameriere's third molar maturity index demonstrated a sensitivity of 0.77% and specificity of 0.96%, while in females, it showed a sensitivity of 0.57% and specificity of 0.92%. Regarding Olze et al.'s stage 0, the sensitivity and specificity values were 0.86% and 0.79% in males, and 0.85% and 0.75% in females, respectively.

CONCLUSION: Although both methods can be used to distinguish individuals below or above the age of 18, the cut-off value suggested by Cameriere's method resulted in a higher rate of type 2 error (false negativity). Therefore, the method proposed by Olze et al., based on the radiographic visibility of the root pulp, can be employed to differentiate between adults and minors in the Turkish population.}, } @article {pmid39008114, year = {2024}, author = {Suresh, S}, title = {Comment on Ma et al.'s "The Preventive Effect of Gentamicin in the Irrigating Solution on Endophthalmitis Caused by Methicillin-Resistant Staphylococcus epidermidis After Phacoemulsification with Intraocular Lens Implantation in Rabbits".}, journal = {Ocular immunology and inflammation}, volume = {32}, number = {10}, pages = {2612-2613}, doi = {10.1080/09273948.2024.2375603}, pmid = {39008114}, issn = {1744-5078}, mesh = {Animals ; *Endophthalmitis/prevention & control/microbiology ; Rabbits ; *Gentamicins/therapeutic use ; *Phacoemulsification ; *Staphylococcus epidermidis/drug effects ; *Staphylococcal Infections/prevention & control/microbiology ; *Eye Infections, Bacterial/prevention & control/microbiology ; *Anti-Bacterial Agents/therapeutic use ; *Lens Implantation, Intraocular ; Therapeutic Irrigation ; Methicillin Resistance ; }, abstract = {In their recent publication, the authors explored the preventive effect of gentamicin in the irrigating solution on endophthalmitis caused by methicillin-resistant Staphylococcus epidermidis (MRSE) after phacoemulsification with intraocular lens (IOL) implantation in rabbits. This letter commends the authors for their innovative approach and discusses the potential of chitosan-based intraocular lenses as a future solution for reducing the incidence of endophthalmitis. Chitosan's natural antibacterial properties, coupled with its capacity for sustained drug release and surface modification, make it a promising material for IOLs. This letter highlights recent advancements and suggests areas for further research to fully realize the potential of chitosan-based IOLs in ocular surgery.}, } @article {pmid39007382, year = {2024}, author = {Huber, TB and Wheeler, RA}, title = {Fixed-node diffusion Monte Carlo shows promise for modeling reaction thermochemistry of hydrocarbon-based radicals.}, journal = {The Journal of chemical physics}, volume = {161}, number = {3}, pages = {}, doi = {10.1063/5.0211903}, pmid = {39007382}, issn = {1089-7690}, abstract = {Reliable thermodynamic and kinetic properties of free radical polymerization reactions are essential for synthesizing both primary polymeric materials and specialty polymers. The computational generation of these data from quantum chemistry requires a time-efficient method capable of capturing the essential physics. One such method, fixed-node diffusion Monte Carlo (FN-DMC) (using single Slater-Jastrow trial wavefunctions), has demonstrated the capability to recover 90%-95% of missing dynamic correlation energy for typical systems. In this study, methyl radical addition to ethylene serves as a simple model to test FN-DMC's ability to calculate enthalpies of reaction and activation energies with different time steps, antisymmetric trial wavefunctions, basis set sizes, and effective core potentials. The FN-DMC computational protocol thus defined for methyl radical addition to ethylene is subsequently benchmarked against Weizmann-1 and experimental reaction enthalpies from Lin et al.'s test set of 21 radical addition and 28 hydrogen abstraction enthalpies. Our findings reveal that FN-DMC consistently generates reaction enthalpies with chemical accuracy, exhibiting mean absolute deviation of 3.5(7) and 1.4(8) kJ/mol from the Weizmann-1 reference for radical addition and hydrogen abstraction reactions, respectively. Given its favorable computational scaling and high degree of parallelizability, we, therefore, recommend more comprehensive testing of FN-DMC with effective core potentials to address more extensive and intricate polymerization reactions and reactions with other radicals.}, } @article {pmid38993137, year = {2024}, author = {Lheem, AJ and Becker, AE}, title = {Culturally Local Perspectives Are Imperative to Scientific Excellence and Health Equity in Eating Disorders Research: Commentary on Monocello et al. (2024).}, journal = {The International journal of eating disorders}, volume = {57}, number = {10}, pages = {2063-2066}, doi = {10.1002/eat.24261}, pmid = {38993137}, issn = {1098-108X}, mesh = {Humans ; *Feeding and Eating Disorders/ethnology/therapy ; *Body Image/psychology ; *Health Equity ; Republic of Korea/ethnology ; Male ; }, abstract = {This commentary discusses a principal contribution of Monocello et al.'s paper presenting a cultural models approach to body fatness perceptions, which provides a rigorous and systematic means of identifying analytic categories that are locally meaningful, in contrast to categories derived from a solely universalizing perspective. In situating their work within an underrepresented population in eating disorders research-young men in South Korea-the authors step beyond the constraints of a universalizing, or etic, framework for probing how body dissatisfaction relates to eating disorder risk. The value of an alternative analytic framework, based on a culturally local, or emic, perspective on how bodies are perceived is demonstrated through the use of a cultural models approach exploring the relationship between culturally defined conceptualizations of body image and eating disorder risk. Understanding such relationships and the meanings attributed to the myriad aspects of body image through locally grounded frameworks provides an essential tool for investigators and clinicians to better understand the lived experience of body dissatisfaction and disordered eating, and also to inform more culturally salient approaches to diagnosis, treatment, and prevention. An emic approach that centers local perspectives and priorities also facilitates participation of communities underrepresented in research in knowledge production.}, } @article {pmid38992702, year = {2024}, author = {Finch, TL and Potthoff, S and May, CR and Girling, M and Perkins, N and Vis, C and Bührmann, L and Etzelmueller, A and van Genugten, CR and Schuurmans, J and Piera-Jiménez, J and Rapley, T and , }, title = {How is tailored implementation undertaken using a self-guided toolkit? Qualitative study of the ItFits-toolkit in the ImpleMentAll project.}, journal = {Implementation science : IS}, volume = {19}, number = {1}, pages = {48}, pmid = {38992702}, issn = {1748-5908}, support = {733025//Horizon 2020/ ; 733025//Horizon 2020/ ; 733025//Horizon 2020/ ; 733025//Horizon 2020/ ; 733025//Horizon 2020/ ; 733025//Horizon 2020/ ; 733025//Horizon 2020/ ; }, mesh = {Humans ; *Qualitative Research ; Australia ; *Implementation Science ; *Cognitive Behavioral Therapy/methods ; Europe ; Internet ; Internet-Based Intervention ; }, abstract = {BACKGROUND: The process of tailored implementation is ill-defined and under-explored. The ItFits-toolkit was developed and subsequently tested as a self-guided online platform to facilitate implementation of tailored strategies for internet-based cognitive behavioural therapy (iCBT) services. In ImpleMentAll, ItFits-toolkit had a small but positive effect on the primary outcome of iCBT normalisation. This paper investigates, from a qualitative perspective, how implementation teams developed and undertook tailored implementation using the toolkit within the trial.

METHODS: Implementation teams in thirteen sites from nine countries (Europe and Australia) used the ItFits-toolkit for six months minimum, consistent with the trial protocol. A qualitative process evaluation was conducted. Descriptive data regarding goals, barriers, strategies, and implementation plans collected within the toolkit informed qualitative data collection in real time. Qualitative data included remote longitudinal interviews (n = 55) with implementation team members (n = 30) and observations of support calls (n = 19) with study sites. Qualitative data were analysed thematically, using a team-based approach.

RESULTS: Implementation teams developed and executed tailored implementation projects across all steps in the toolkit process. Working in a structured way but with room for flexibility, decisions were shaped by team members' ideas and goals, iterative stakeholder engagement, internal and external influences, and the context of the ImpleMentAll project. Although teams reported some positive impacts of their projects, 'time', both for undertaking the work, and for seeing project impacts, was described as a key factor in decisions about implementation strategies and assessments of success.

CONCLUSION: This study responds directly to McHugh et al.'s (2022) call for empirical description of what implementation tailoring looks like in action, in service settings. Self-guided facilitation of tailored implementation enables implementers in service settings to undertake tailoring within their organisations. Implementation tailoring takes considerable time and involves detailed work but can be supported through the provision of implementation science informed guidance and materials, iterative and ongoing stakeholder engagement, and working reflectively in response to external influencing factors. Directions for advancement of tailored implementation are suggested.}, } @article {pmid38992500, year = {2024}, author = {Boyle, A and McDonald, I and Wall, D}, title = {Response to Mounessa et al.'s "Commonly prescribed medications associated with alopecia''.}, journal = {Journal of the American Academy of Dermatology}, volume = {91}, number = {6}, pages = {e161}, doi = {10.1016/j.jaad.2024.06.077}, pmid = {38992500}, issn = {1097-6787}, } @article {pmid38990849, year = {2024}, author = {Cobos, PL and Quintero, MJ and López, FJ and Luque, D and Ciria, LF and Morís, YJ}, title = {Intolerance of uncertainty does not significantly predict decisions about delayed, probabilistic rewards: A failure to replicate Luhmann, C. C., Ishida, K., & Hajcak, G. (2011).}, journal = {PloS one}, volume = {19}, number = {7}, pages = {e0298503}, pmid = {38990849}, issn = {1932-6203}, mesh = {Humans ; Uncertainty ; *Reward ; Male ; Female ; Adult ; *Decision Making ; Young Adult ; Middle Aged ; Adolescent ; }, abstract = {Intolerance of Uncertainty (IU) is thought to lead to maladaptive behaviours and dysfunctional decision making, both in the clinical and healthy population. The seminal study reported by Luhmann and collaborators in 2011 showed that IU was negatively associated with choosing a delayed, but more certain and valuable, reward over choosing an immediate, but less certain and valuable, reward. These findings have been widely disseminated across the field of personality and individual differences because of their relevance to understand the role of IU in maladaptive behaviours in anxiety-related disorders. We conducted a study to replicate and extend Luhmann et al.'s results with a sample of 313 participants, which exceeded the size necessary (N = 266) to largely improve the statistical power of the original study by using the small telescopes approach. The results of our well powered study strongly suggest that the relationship between IU and the tendency to prefer an immediate, but less certain and less valuable reward is virtually negligible. Consequently, although this relationship cannot be definitely discarded, we conclude that it cannot be detected with Luhmann et al.'s (2011) decision-making task.}, } @article {pmid38985783, year = {2024}, author = {Gamache, D and Leclerc, P and Côté, A and Théberge, D and Savard, C}, title = {Broader Issues in Test Translation and Validation: A Commentary Inspired by Macina et al. (2023).}, journal = {Journal of personality assessment}, volume = {106}, number = {6}, pages = {724-726}, doi = {10.1080/00223891.2024.2375213}, pmid = {38985783}, issn = {1532-7752}, mesh = {Humans ; *Psychometrics ; *Personality Disorders/diagnosis ; Reproducibility of Results ; Personality Assessment/standards ; }, abstract = {Macina et al. (2023) recently reported mixed results on the German translation of the Self and Interpersonal Functioning Scale (SIFS). By focusing on suboptimal indices of structural validity, they recommended choosing other available instruments over the SIFS in future research on personality impairment. Reflecting on Macina et al.'s overall conclusions inspired us to consider broader issues in the field of personality impairment assessment. In this commentary, we discuss some issues regarding test translation and validity raised by Macina et al.'s article. We advise against assuming equivalence between original and translated versions of a test and discuss some caveats regarding comparison between different instruments based on structural validity. We also call into question whether the latter should be the litmus test for judging the quality of a measure. Finally, we discuss how the proliferation of personality impairment measures can benefit the broader field. Notably, this would allow moving toward a "what works for whom" approach that considers the match between psychometric property, desired use of the instrument, and characteristics of the target population.}, } @article {pmid38976420, year = {2024}, author = {McCauley, TG and McAuliffe, WHB and McCullough, ME}, title = {Does empathy promote helping by activating altruistic motivation or concern about social evaluation? A direct replication of Fultz et al. (1986).}, journal = {Emotion (Washington, D.C.)}, volume = {24}, number = {8}, pages = {1868-1884}, doi = {10.1037/emo0001339}, pmid = {38976420}, issn = {1931-1516}, support = {//John Templeton Foundation/ ; //Army Research Institute/ ; }, mesh = {Humans ; *Empathy/physiology ; *Altruism ; Female ; Male ; *Motivation ; Young Adult ; Adult ; *Helping Behavior ; Adolescent ; Social Behavior ; }, abstract = {When people experience empathy for a needy stranger, efforts to help are often not far behind. But does empathy actually cause prosocial behavior? And if so, does it activate genuine concern or more self-interested motivations? To rule out the alternative hypothesis that empathy motivates prosocial behavior by generating fear of social disapproval for acting selfishly, Fultz et al. (1986) manipulated empathy for a lonely stranger using perspective-taking instructions; they also manipulated whether subjects believed their decision to help would remain anonymous. However, Fultz et al. conducted their experiment decades ago, with few subjects, and before some potentially important cultural changes in college students' values and social lives. Here, in a preregistered replication with 280 undergraduates, we tested Fultz et al.'s key assertions. The perspective-taking and social evaluation manipulations influenced scores on the manipulation check measures mostly in theory-consistent ways but did not significantly influence helping. Consistent with theory, empathy was positively associated with prosocial behavior. We also found evidence that endorsement of the principle of care reflects genuine concern for needy strangers and that moral identity symbolization reflects a desire to help in order to avoid social disapproval. We consider these results a partially successful replication of key tenets of the empathy-altruism hypothesis, though questions remain about the conditions under which perspective-taking promotes prosocial behavior and about the generalizability of our findings to populations beyond undergraduate women circa 1986. Our results also help illuminate the motivational underpinnings of two individual differences that predicted prosocial behavior in previous research. (PsycInfo Database Record (c) 2024 APA, all rights reserved).}, } @article {pmid38972036, year = {2024}, author = {Zhang, J and Fan, R and Mao, C and Zhou, X and Zhang, Q and Li, S and Zhuang, Z}, title = {Artificial sweetener and respiratory system cancer: A Mendelian randomization analysis.}, journal = {Clinical nutrition ESPEN}, volume = {63}, number = {}, pages = {259-266}, doi = {10.1016/j.clnesp.2024.06.008}, pmid = {38972036}, issn = {2405-4577}, mesh = {Humans ; *Mendelian Randomization Analysis ; *Polymorphism, Single Nucleotide ; *Sweetening Agents ; Aspartame ; Mouth Neoplasms/genetics ; Pharyngeal Neoplasms/genetics ; Taste ; Reproducibility of Results ; }, abstract = {BACKGROUND & AIMS: The association between artificial sweeteners and various cancers has been investigated, but their relationship with respiratory system cancers remains uncertain. To address this knowledge gap, we conducted a comprehensive Mendelian Randomization (MR) analysis.

METHODS: We looked for SNPs associated with artificial sweetener intake and respiratory system cancers from the IEU OpenGWAS project, as well as SNPs related to sweet taste in artificial sweeteners from Hwang et al.'s study. Rigorous quality control procedures were implemented to select instrumental Single Nucleotide Polymorphisms that were closely linked to artificial sweetener intake. To ensure the reliability of our findings, we employed five different analytical methods, with the inverse variance weighting method being the primary approach. Additionally, we thoroughly assessed heterogeneity, pleiotropy, and sensitivity. Finally, we conducted Multivariable Mendelian Randomization (MVMR) to validate our results.

RESULTS: Intake of artificial sweetener added to cereal showed a positive association with malignant neoplasm of the lip, oral cavity, and pharynx (OR: 1027.54; 95% CI: 4.8-219994.46; P = 0.011), and the result was also confirmed by the MVMR analysis. In addition, better perceived intensity of aspartame was negatively associated with cancers in these regions (OR: 0.49; 95% CI: 0.28-0.88; P = 0.016). Intake of artificial sweetener added to coffee or tea was not related with respiratory system cancer.

CONCLUSIONS: Our research offers evidence that the consumption of artificial sweeteners in cereals could increase the risk of cancers in the lip, oral cavity, and pharynx. Additionally, a greater sensitivity to the taste of aspartame may lower this risk.}, } @article {pmid38968276, year = {2024}, author = {El Ouardi, L and Yeou, M}, title = {Are Personal and Reflexive Pronouns Dissociated in Agrammatic Comprehension? An Individual Participant Meta-Analysis With Clinical Implications.}, journal = {American journal of speech-language pathology}, volume = {33}, number = {6S}, pages = {3218-3235}, pmid = {38968276}, issn = {1558-9110}, mesh = {Humans ; Aphasia, Broca/physiopathology ; *Comprehension/physiology ; Semantics ; }, abstract = {PURPOSE: This study had three objectives: (a) to verify if Grodzinsky et al.'s (1993) findings of worse comprehension of personal than reflexive pronouns can be replicated in a larger meta-analysis of individual participant data, (b) to examine if the heterogeneity found in the patterns of pronoun comprehension in agrammatism can be attributed to task effects, and (c) to evaluate the risk of bias in the reviewed studies.

METHOD: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a systematic literature search was performed to identify studies examining the personal-reflexive pronoun dissociation in agrammatic comprehension. Seven studies met the search criteria and were included in the meta-analysis. For each participant, individual accuracy scores for the comprehension of personal and reflexive pronouns were extracted in addition to information on the study methods. Individual accuracy data were analyzed using the Fisher's exact test and the binomial test. The risk of bias in the studies was assessed using an adapted version of the Newcastle-Ottawa Quality Assessment Scale.

RESULTS: The meta-analysis had three main findings: (a) The majority of the persons with agrammatic aphasia (89%) had no dissociation between the comprehension of personal and reflexive pronouns; (b) 8% revealed a pattern consistent with a neuropsychological dissociation, faring worse on the comprehension of personal than reflexive pronouns; and (c) 2% performed worse on reflexive than personal pronouns. The type of the task used affected pronoun comprehension accuracy and accounted for the heterogeneity in the patterns of pronoun comprehension attested across the different participants.

CONCLUSIONS: Taken together, the meta-analysis did not support a dissociation between personal and reflexive pronoun comprehension in agrammatic comprehension. When confirmed, the dissociation was driven by task effects. The clinical implications of these findings were discussed together with implications to minimize the risk of bias in future examinations of the topic.}, } @article {pmid38967835, year = {2024}, author = {Brusselaers, N}, title = {Author's Reply to Avó-Baião et al.'s Comment on "Maternal and Early-Life Exposure to Antibiotics and the Risk of Autism and Attention-Deficit Hyperactivity Disorder in Childhood: A Swedish Population-Based Cohort Study".}, journal = {Drug safety}, volume = {47}, number = {8}, pages = {823-825}, pmid = {38967835}, issn = {1179-1942}, mesh = {Humans ; *Attention Deficit Disorder with Hyperactivity/drug therapy/epidemiology ; Female ; Pregnancy ; Sweden/epidemiology ; *Anti-Bacterial Agents/adverse effects ; *Autistic Disorder/epidemiology/chemically induced ; *Prenatal Exposure Delayed Effects/chemically induced/epidemiology ; Child ; Cohort Studies ; Risk Factors ; }, } @article {pmid38967065, year = {2024}, author = {Zhu, Y and Bi, Y and Zhu, T}, title = {Mendelian randomization highlights sleep disturbances mediated the effect of depression on chronic pain.}, journal = {Brain and behavior}, volume = {14}, number = {7}, pages = {e3596}, pmid = {38967065}, issn = {2162-3279}, mesh = {Humans ; *Chronic Pain/genetics/physiopathology ; *Mendelian Randomization Analysis ; *Depressive Disorder, Major/genetics/physiopathology ; *Genome-Wide Association Study ; Sleep Wake Disorders/genetics/epidemiology/physiopathology ; Sleep Initiation and Maintenance Disorders/genetics/epidemiology ; Fibromyalgia/genetics ; Genetic Predisposition to Disease ; Mediation Analysis ; }, abstract = {INTRODUCTION: Depression and chronic pain are significant contributors to the global burden of disease. Previous research has revealed complex relationships between these two conditions, which may be influenced by sleep quality. However, observational studies have limitations, including confounding factors and reverse causation. This study aims to explore the mediating effects of sleep on the relationship between depression and chronic pain using Mendelian randomization (MR).

METHODS: We conducted a two-step, two-sample MR study using mediation analysis. We obtained major depressive disorder (MDD) Genome-Wide Association Studdies (GWAS) data from Wray et al.'s GWAS meta-analysis. Phenotypic data related to sleep were collected from the UK Biobank. Chronic pain data were obtained from the Finnish database.

RESULTS: MR analysis revealed significant genetic associations between MDD and chronic localized pain [IVW: odds ratio (OR) = 1.26, 95% confidence interval (CI) = 1.16-1.38, p = 2.52 × 10[-7]] as well as fibromyalgia (IVW: OR = 2.17, 95% CI = 1.34-3.52, p = .002). Genetic susceptibility for MDD was also associated with insomnia (IVW: OR = 1.10, 95% CI = 1.06-1.13, p = 3.57 × 10[-8]) and self-reported short sleep duration (IVW: OR = 1.03, 95% CI = 1.00-1.06, p = .047). The mediating effects of insomnia and fibromyalgia on the pathway from depression to chronic regional pain were 1.04 and 1.03, respectively, with mediation proportions of 12.8% and 15.2%. Insomnia mediated the pathway between depression and fibromyalgia with an effect of 1.12, accounting for 15.2% of the total effect.

CONCLUSION: This two-step MR analysis strengthens the evidence of genetic predictive associations between depression and chronic pain, highlighting the mediating roles of insomnia and short sleep duration. It further elucidates the specific roles of distinct sleep disorders, differentiating insomnia and short sleep duration from other sleep-related phenotypes.}, } @article {pmid38955505, year = {2024}, author = {Yuill, C and Sinesi, A and Meades, R and Williams, LR and Delicate, A and Cheyne, H and Maxwell, M and Shakespeare, J and Alderdice, F and Leonard, R and Ayers, S and , }, title = {Women's experiences and views of routine assessment for anxiety in pregnancy and after birth: A qualitative study.}, journal = {British journal of health psychology}, volume = {29}, number = {4}, pages = {958-971}, doi = {10.1111/bjhp.12740}, pmid = {38955505}, issn = {2044-8287}, mesh = {Humans ; Female ; Pregnancy ; *Qualitative Research ; Adult ; *Anxiety/psychology ; Pregnancy Complications/psychology ; Young Adult ; Postpartum Period/psychology ; }, abstract = {BACKGROUND: Anxiety in pregnancy and postnatally is highly prevalent but under-recognized. To identify perinatal anxiety, assessment tools must be acceptable to women who are pregnant or postnatal.

METHODS: A qualitative study of women's experiences of anxiety and mental health assessment during pregnancy and after birth and views on the acceptability of perinatal anxiety assessment. Semi-structured interviews were conducted with 41 pregnant or postnatal women. Results were analysed using Sekhon et al.'s acceptability framework, as well as inductive coding of new or emergent themes.

RESULTS: Women's perceptions of routine assessment for perinatal anxiety were generally favourable. Most participants thought assessment was needed and that the benefits outweighed potential negative impacts, such as unnecessary referrals to specialist services. Six themes were identified of: (1) Raising awareness; (2) Improving support; (3) Surveillance and stigma; (4) Gatekeeping; (5) Personalized care and (6) Trust. Assessment was seen as a tool for raising awareness about mental health during the perinatal period and a mechanism for normalizing discussions about mental health more generally. However, views on questionnaire assessments themselves were mixed, with some participants feeling they could become an administrative 'tick box' exercise that depersonalizes care and does not provide a space to discuss mental health problems.

CONCLUSION: Routine assessment of perinatal anxiety was generally viewed as positive and acceptable; however, this was qualified by the extent to which it was informed and personalized as a process. Approaches to assessment should ideally be flexible, tailored across the perinatal period and embedded in continuity of care.}, } @article {pmid38951787, year = {2024}, author = {Otiso, L and Alhassan, Y and Odhong, T and Onyango, B and Muturi, N and Hemingway, C and Murray, L and Ogwang, E and Okoth, L and Oguche, M and Doyle, V and Fomuso, N and Taegtmeyer, M}, title = {Exploring acceptability, opportunities, and challenges of community-based home pregnancy testing for early antenatal care initiation in rural Kenya.}, journal = {BMC public health}, volume = {24}, number = {1}, pages = {1742}, pmid = {38951787}, issn = {1471-2458}, support = {MR/T003324/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Humans ; Female ; Kenya ; Pregnancy ; *Prenatal Care ; Adult ; *Patient Acceptance of Health Care/statistics & numerical data/psychology ; Adolescent ; Young Adult ; *Rural Population ; *Pregnancy Tests ; Community Health Workers ; Qualitative Research ; Interviews as Topic ; Home Care Services ; }, abstract = {BACKGROUND: Many women in low- and middle-income countries, including Kenya, access antenatal care (ANC) late in pregnancy. Home pregnancy testing can enable women to detect pregnancy early, but it is not widely available. Our study explored the acceptability and potential of home pregnancy testing delivered by community health volunteers (CHV) on antenatal care initiation in rural Kenya.

METHODS: This study was part of a public health intervention to improve uptake and quality of ANC. Between November and December 2020, we conducted 37 in-depth interviews involving women who tested positive or negative for a urine pregnancy test provided by CHVs; CHVs and their supervisors involved in the delivery of the pregnancy tests; facility healthcare workers; and key informants. Using Sekhon et al.'s framework of acceptability, the interviews explored participants' perceptions and experiences of home pregnancy testing, including acceptability, challenges, and perceived effects on early ANC uptake. Data were analysed thematically in NVivo12 software.

RESULTS: Home pregnancy testing was well-received by women who trusted test results and appreciated the convenience and autonomy it offered. Adolescents cherished the privacy, preferring home testing to facility testing which could be a stigmatising experience. Testing enabled earlier pregnancy recognition and linkage to ANC as well as reproductive decision-making for those with undesired pregnancies. Community delivery of the test enhanced the reputation and visibility of the CHVs as credible primary care providers. CHVs in turn were motivated and confident to deliver home pregnancy testing and did not find it as an unnecessary burden; instead, they perceived it as a complement to their work in providing ANC in the community. Challenges identified included test shortages, confidentiality and safeguarding risks, and difficulties accessing facility-based care post-referral. Newly identified pregnant adolescents hesitated to seek ANC due to stigma, fear of reprimand, unwanted parental notification, and perceived pressure from healthcare workers to keep the pregnancy.

CONCLUSION: Home pregnancy testing by CHVs can improve early ANC initiation in resource-poor settings. Mitigating privacy, confidentiality, and safeguarding concerns is imperative. Additional support for women transitioning from pregnancy identification to ANC is essential to ensure appropriate care. Future research should focus on integrating home pregnancy testing into routine community health services.}, } @article {pmid38949073, year = {2024}, author = {He, J and Barnhart, WR}, title = {A Call for More Culture-Based Research to Understand Body Dissatisfaction and Disordered Eating in Men: Commentary on Monocello et al. (2024).}, journal = {The International journal of eating disorders}, volume = {57}, number = {10}, pages = {2060-2062}, doi = {10.1002/eat.24249}, pmid = {38949073}, issn = {1098-108X}, support = {2023SC0028//Science, Technology, and Innovation Commission of Shenzhen Municipality/ ; 72204208//National Natural Science Foundation of China/ ; }, mesh = {Humans ; Male ; *Feeding and Eating Disorders/psychology/ethnology ; *Body Dissatisfaction/psychology ; Body Image/psychology ; Republic of Korea/ethnology ; Culture ; }, abstract = {Using culture-based approaches, Monocello et al. revealed that young Korean men generally shared the same perceptions of fatness, including three categories ("too thin," "balanced," and "too fat"). The "balanced" category was most consistent with local South Korean culture, and the "too fat" category was associated with higher body dissatisfaction and disordered eating. Even though cultural differences in body ideals are an essential factor to consider in the development of body dissatisfaction and disordered eating, little research has applied culture-based approaches to explore body ideals in men, including how these ideals may be related to men's body image or eating behaviors. Thus, Monocello et al.'s work is a timely and vital contribution to the literature. In this commentary, we expand on Monocello et al.'s work by not only illustrating the roles of local cultures but also introducing the potential influences of external cultures via acculturation in shaping body ideals which, in turn, contribute to body dissatisfaction and disordered eating in men. We also provide future research directions to call for more culture-based research to understand body dissatisfaction and disordered eating among men in different cultural contexts.}, } @article {pmid38947464, year = {2024}, author = {Yaşar Dinçer, FC and Yirmibeşoğlu, G and Bilişli, Y and Arık, E and Akgün, H}, title = {Trends and emerging research directions of sustainable aviation: A bibliometric analysis.}, journal = {Heliyon}, volume = {10}, number = {11}, pages = {e32306}, pmid = {38947464}, issn = {2405-8440}, abstract = {This study aims to conduct a bibliometric analysis to determine trends and emerging research directions of sustainable aviation between 2001 and 2023. 726 studies indexed in the Web of Science were examined through VOSviewer software. Science mapping and performance analyses were implemented to demonstrate a systematic quantitative review and the characteristics of the research area. Moreover, by using co-occurrence of keywords, citation, bibliographic coupling, co-authorship, and co-citation analyses, the trends of the research area were revealed in detail. Findings indicated that the publications on sustainable aviation literature were mainly conducted between 2020 and 2023. Research areas of the publications were mainly on "engineering" and "energy fuels". In terms of number of the publications, "International Journal of Sustainable Aviation Fuel" was the most productive source and Heyne was the most productive author. Co-occurrence analysis demonstrated that "sustainable aviation fuel" was the most frequently used keyword. Furthermore, sustainable aviation research has shifted in focus toward more challenging and technology-oriented research over time. Citation analysis indicated that the most cited author was Heyne, the most cited study was Ma et al.'s study on "Aviation biofuel from renewable resources: routes, opportunities and challenges" and the most cited sources was "Energy". Among countries, the U.S.A was the most cited country and Chinese Academy of Sciences was the most cited organization. Bibliographic analysis showed that Heyne was the author with the highest connection strength. Co-authorship analysis demonstrated that Washington State University was the most collaborative organization. Finally, co-citation analysis of cited references indicated that fundamental subjects and related references were mainly sustainable aviation fuel, production of sustainable aviation fuel and its use in aviation studies. It is anticipated that results of this study would contribute to sustainable aviation research and ensure guidance and new perspectives for future research topics and directions on sustainable aviation.}, } @article {pmid38939220, year = {2024}, author = {Galla, B and Karanam, A and Pelakh, A and Goldberg, SB}, title = {Adolescents do not benefit from universal school-based mindfulness interventions: a reanalysis of Dunning et al. (2022).}, journal = {Frontiers in psychology}, volume = {15}, number = {}, pages = {1384531}, pmid = {38939220}, issn = {1664-1078}, support = {K23 AT010879/AT/NCCIH NIH HHS/United States ; R24 AT012845/AT/NCCIH NIH HHS/United States ; }, abstract = {Are universal school-based mindfulness interventions an effective way to reduce risk for mental disorders and improve adolescents' lives? To answer this question, we reanalyzed data from Dunning et al.'s (2022) meta-analysis of randomized controlled trials of mindfulness interventions delivered to children and adolescents. Though Dunning et al. (2022) reported some benefits of universal mindfulness interventions, their analysis did not examine adolescents separately from children. Consequently, their conclusions may not entirely reflect the effectiveness of universal mindfulness interventions specifically for adolescents, a developmental period when mental disorders are known to increase. Using their open-access data tables, we tested impacts of 22 randomized controlled trials (N = 16,558) on eight outcome categories-anxiety/stress, attention, depression, executive functioning, mindfulness, negative behavior, social behavior, and wellbeing-at immediate post-test and longest follow-up. Our reanalysis shows that when compared to passive controls, mindfulness interventions significantly reduced trait mindfulness (d = -0.10). When compared to active controls, mindfulness interventions significantly improved anxiety/stress (d = 0.17) and wellbeing (d = 0.10). When compared to all controls combined, mindfulness interventions did not significantly improve any outcome (ds = 0.01 to 0.26). No effects of mindfulness interventions were observed at follow-up assessment. Overall, results of our analysis cast doubt about the value of existing school-based mindfulness interventions as a universal prevention strategy for adolescents.}, } @article {pmid38935661, year = {2024}, author = {Verschuuren, AEH and Tankink, JB and Postma, IR and Bergman, KA and Goodarzi, B and Feijen-de Jong, EI and Erwich, JJHM}, title = {Suboptimal factors in maternal and newborn care for refugees: Lessons learned from perinatal audits in the Netherlands.}, journal = {PloS one}, volume = {19}, number = {6}, pages = {e0305764}, pmid = {38935661}, issn = {1932-6203}, mesh = {Humans ; *Refugees ; Female ; Netherlands ; Pregnancy ; Infant, Newborn ; Adult ; Retrospective Studies ; *Perinatal Care/standards ; Pregnancy Outcome ; Health Services Accessibility ; Quality of Health Care ; Young Adult ; Patient Acceptance of Health Care ; }, abstract = {INTRODUCTION: Refugees and their healthcare providers face numerous challenges in receiving and providing maternal and newborn care. Research exploring how these challenges are related to adverse perinatal and maternal outcomes is scarce. Therefore, this study aims to identify suboptimal factors in maternal and newborn care for asylum-seeking and refugee women and assess to what extent these factors may contribute to adverse pregnancy outcomes in the Netherlands.

METHODS: We conducted a retrospective analysis of national perinatal audit data from 2017 to 2019. Our analysis encompassed cases with adverse perinatal and maternal outcomes in women with a refugee background (n = 53). Suboptimal factors in care were identified and categorized according to Binder et al.'s Three Delays Model, and the extent to which they contributed to the adverse outcome was evaluated.

RESULTS: We identified 29 suboptimal factors, of which seven were related to care-seeking, six to the accessibility of services, and 16 to the quality of care. All 53 cases contained suboptimal factors, and in 67.9% of cases, at least one of these factors most likely or probably contributed to the adverse perinatal or maternal outcome.

CONCLUSION: The number of suboptimal factors identified in this study and the extent to which they contributed to adverse perinatal and maternal outcomes among refugee women is alarming. The wide range of suboptimal factors identified provides considerable scope for improvement of maternal and newborn care for refugee populations. These findings also highlight the importance of including refugee women in perinatal audits as it is essential for healthcare providers to better understand the factors associated with adverse outcomes to improve the quality of care. Adjustments to improve care for refugees could include culturally sensitive education for healthcare providers, increased workforce diversity, minimizing the relocation of asylum seekers, and permanent reimbursement of professional interpreter costs.}, } @article {pmid38920439, year = {2024}, author = {López-Higes, R and Rubio-Valdehita, S and Fernandes, SM and Rodrigues, PFS}, title = {Differentiation between Normal Cognition and Subjective Cognitive Decline in Older Adults Using Discrepancy Scores Derived from Neuropsychological Tests.}, journal = {Geriatrics (Basel, Switzerland)}, volume = {9}, number = {3}, pages = {}, pmid = {38920439}, issn = {2308-3417}, support = {RTI2018-098762-B-C31//Spanish Ministry of Science, Innovation and Universities/ ; }, abstract = {Several studies have reported subtle differences in cognition between individuals with subjective cognitive decline (SCD) compared to those with normal cognition. This study aimed to (i) identify these differences using discrepancy scores (e.g., categorial-phonemic verbal fluency performance) derived from neuropsychological tests in three cognitive domains (memory: Wechsler's Word List and Digits; executive functions: Stroop and verbal fluency; and language: BNT and ECCO_Senior) and (ii) determine which discrepancy scores are significant for classification. Seventy-five older adults were included: 32 who were labeled SCD+ (age 71.50 ± 5.29), meeting Jessen et al.'s criteria, and 43 in the normal cognition group (SCD-; age 69.81 ± 4.62). Both groups completed a protocol including screening and the specified neuropsychological tests. No differences were found between the groups in their age, education, episodic memory, global cognitive state, or mood. Significant differences between the groups were observed regarding the discrepancy scores derived from BNT (naming) and ECCO_Senior (sentence comprehension). These scores accurately classified participants (71.6%), with ECCO_Senior having a primary role. ROC curves indicated a poor-to-fair model quality or diagnostic accuracy (AUC_BNT = 0.690; AUC_ECCO = 0.722). In conclusion, discrepancy scores in the language domain are important for distinguishing between individuals with SCD and normal cognition, complementing previous findings in this domain. However, given their relatively poor diagnostic accuracy, they should be used with caution as part of a more detailed neuro-psychological assessment.}, } @article {pmid38919633, year = {2024}, author = {Findeis, H and Strauß, M and Kröber, HL}, title = {The TCO concept in German forensic homicide offenders with schizophrenia spectrum disorders - new findings from a file-based, retrospective cross-sectional study.}, journal = {Frontiers in psychiatry}, volume = {15}, number = {}, pages = {1404263}, pmid = {38919633}, issn = {1664-0640}, abstract = {INTRODUCTION: There is evidence that there is a small group of people with schizophrenia spectrum disorders who are more likely to commit homicide than those in the general population. However, there is limited knowledge about the psychopathology that leads to homicide in this group. The aim of this study was to examine two commonly used definitions of the Threat/Control-Override (TCO) concept, which aims to identify a certain risk of serious violence in patients with schizophrenia spectrum disorders.

METHODS: This is a sub analysis of a file-based, retrospective and exploratory cross-sectional study. All forensic homicide offenders with schizophrenia spectrum disorders who were detained at the Forensic Hospital Berlin as of 31 December 2014 were examined for the occurrence of TCO according to two commonly used definitions.

RESULTS: Of a total of 419 forensic patients with schizophrenia spectrum disorders, 78 committed homicide (18.6%). The forensic homicide offenders with schizophrenia spectrum disorders were characterised by being male, unemployed, single and having committed (attempted) manslaughter. Irrespective of the definition used, the entire TCO complex was present in less than a third of the sample. In both definitions, Threat symptoms were slightly less frequent than Control-Override symptoms. While Threat symptoms occurred less frequently in Stompe et al.'s definition, Control-Override symptoms were the most common. With regard to Kröber's definition of Threat and Control-Override, the situation is exactly the opposite.

DISCUSSION: Regarding the entire TCO complex, Kröber's definition seems a little more open and Stompe et al.'s more strict (38.5% vs. 35.9%). Since TCO only occurs in about one third of the subjects in both definitions, neither definition appears to be conclusive. A combination with proportions from both definitions could be a contribution to a future definition of TCO. The present study provides scarcely published primary data on psychopathology in homicide offenders with schizophrenia spectrum disorders, especially on the much discussed TCO concept in two definitions. In order to determine the most useful definition of TCO, to avoid false positives and to identify clear psychopathological risk symptoms, larger samples and comparative studies with offenders and non-offenders should be conducted in the future.}, } @article {pmid38917177, year = {2024}, author = {Engels, B and Kloek, CJJ and Sol, ME and Bolster, EAM and Kotte, EMW and Wittink, H and Engelbert, RHH and Gorter, JW and Bloemen, MAT}, title = {Exploring needs and requirements for a prototype device measuring physical activity in pediatric physical therapy: A qualitative study.}, journal = {PloS one}, volume = {19}, number = {6}, pages = {e0305968}, pmid = {38917177}, issn = {1932-6203}, mesh = {Humans ; Child ; Adolescent ; Male ; Female ; *Qualitative Research ; *Exercise ; Physical Therapy Modalities/instrumentation ; Adult ; Parents ; Physical Therapists ; Developmental Disabilities/therapy/rehabilitation ; }, abstract = {AIMS: To analyze needs and requirements of Pediatric Physical Therapists (PPTs), parents, children and adolescents with and without developmental disabilities in the future use of an activity monitor prototype (AM-p) in everyday clinical practice.

METHODS: Qualitative exploratory study with a thematic analysis approach, based on Braun and Clarke's six steps. Codes derived from the analysis and central themes were collated, based on Fleuren et al.'s groupings of determinants.

RESULTS: We interviewed 25 PPTs, 12 parents, and 12 children and adolescents. Within four groupings of determinants, we found nine themes: 1) development of information materials; 2) application: output visualization and ease of use; 3) design; 4) relevance and acceptance; 5) shared decision-making; 6) compatibility in daily living; 7) finances, 8) time, and 9) legislation and regulations.

CONCLUSIONS: End-users have similar basic needs, with individual fine-tuning to be addressed during further development of the AM-p. A child-friendly design, information material, and an easy-to-use application to read and interpret results, need to be developed. Efficient training for PPTs is important for the use of the AM-p and analysis of results. Communication between PPTs and children as well as parents enhances shared decision-making. We recommend involving diverse end-users to enable maximum customization of the AM-p.}, } @article {pmid38913725, year = {2024}, author = {Marsh, JE and Hurlstone, MJ and Marois, A and Ball, LJ and Moore, SB and Vachon, F and Schlittmeier, SJ and Röer, JP and Buchner, A and Aust, F and Bell, R}, title = {Changing-state irrelevant speech disrupts visual-verbal but not visual-spatial serial recall.}, journal = {Journal of experimental psychology. Learning, memory, and cognition}, volume = {50}, number = {11}, pages = {1772-1790}, doi = {10.1037/xlm0001360}, pmid = {38913725}, issn = {1939-1285}, support = {//Bial Foundation/ ; //Deutscher Akademischer Austauschdienst/ ; //University of Central Lancashire/ ; }, mesh = {Humans ; *Mental Recall/physiology ; Young Adult ; Female ; Adult ; Male ; *Serial Learning/physiology ; *Memory, Short-Term/physiology ; *Attention/physiology ; Space Perception/physiology ; Visual Perception/physiology ; Speech/physiology ; Adolescent ; Pattern Recognition, Visual/physiology ; }, abstract = {In an influential article, Jones et al. (1995) provide evidence that auditory distraction by changing relative to repetitive auditory distracters (the changing-state effect) did not differ between a visual-verbal and visual-spatial serial recall task, providing evidence for an amodal mechanism for the representation of serial order in short-term memory that transcends modalities. This finding has been highly influential for theories of short-term memory and auditory distraction. However, evidence vis-à-vis the robustness of this result is sorely lacking. Here, two high-powered replications of Jones et al.'s (1995) crucial Experiment 4 were undertaken. In the first partial replication (n = 64), a fully within-participants design was adopted, wherein participants undertook both the visual-verbal and visual-spatial serial recall tasks under different irrelevant sound conditions, without a retention period. The second near-identical replication (n = 128), incorporated a retention period and implemented the task-modality manipulation as a between-participants factor, as per the original Jones et al. (1995; Experiment 4) study. In both experiments, the changing-state effect was observed for visual-verbal serial recall but not for visual-spatial serial recall. The results are consistent with modular and interference-based accounts of distraction and challenge some aspects of functional equivalence accounts. (PsycInfo Database Record (c) 2024 APA, all rights reserved).}, } @article {pmid38913707, year = {2024}, author = {Hennessy, S and Greer, T and Narayanan, S and Habibi, A}, title = {Unique affective profile of music-evoked nostalgia: An extension and conceptual replication of Barrett et al.'s (2010) study.}, journal = {Emotion (Washington, D.C.)}, volume = {24}, number = {8}, pages = {1803-1825}, doi = {10.1037/emo0001389}, pmid = {38913707}, issn = {1931-1516}, support = {//University of Southern California; Department of Psychology/ ; }, mesh = {Humans ; Female ; Male ; Adult ; *Music ; *Personality/physiology ; *Affect/physiology ; Young Adult ; Middle Aged ; Arousal/physiology ; Emotions/physiology ; Adolescent ; }, abstract = {Nostalgia is a mixed emotion, often evoked by music. This study sought to conceptually replicate and extend Barrett et al.'s (see record 2010-09991-008) pioneering work exploring music-evoked nostalgia, where the authors identified person- and context-level predictors of the experience of nostalgia in music. In a sample of 582 adults across the United States, we identified self-selected nostalgic and musically matched nonnostalgic, familiar songs for each individual, using an online survey in 2021. The participants listened to music and indicated feelings of valence and arousal, followed by assessments of affect (Positive and Negative Affect Schedule, Short Form) and personality (Ten-Item Personality Inventory, Brief Affective Neuroscience Personality Scales, and Southampton Nostalgia Scale). Nostalgic songs were rated higher in valence and arousal than familiar, nonnostalgic control songs, and higher in mixed valence in some metrics. Individuals with higher trait-level Trait Nostalgia reported higher nostalgia ratings across nostalgic and control songs. Interactions between context- and person-level factors indicated that personality influenced the felt valence and arousal profile of music-evoked nostalgia, distinct from familiar control music. While some personality types found nostalgic music to make them feel more aroused and positive (those high in care, trait nostalgia, anger), others felt more negative while listening (those high in sadness). Last, we extend the personality profile of a highly nostalgic person; trait-level Trait Nostalgia was associated with care, play, agreeableness, extraversion, and neuroticism. We demonstrate affective and person-level contributors to music-evoked nostalgia observed in Barrett et al.'s (2010) hold even when controlling for familiarity and musical features. We provide novel insights on complex interactions supporting this emotion, in a larger and more diverse sample with personalized stimuli. (PsycInfo Database Record (c) 2024 APA, all rights reserved).}, } @article {pmid38903557, year = {2023}, author = {Grant, M and Bhana, A and Kathree, T and Khuzwayo, N and van Rensburg, AJ and Mthethwa, L and Gigaba, S and Ntswe, E and Luvuno, Z and Petersen, I}, title = {The feasibility of a Community Mental Health Education and Detection (CMED) tool in South Africa.}, journal = {SSM. Mental health}, volume = {3}, number = {}, pages = {}, pmid = {38903557}, issn = {2666-5603}, support = {U19 MH113191/MH/NIMH NIH HHS/United States ; }, abstract = {BACKGROUND: Poor mental health literacy, misinformation about treatment and stigma result in low demand for mental health services in low-and middle-income countries. Community-based interventions that raise mental health awareness and facilitate detection of mental health conditions, are instrumental in increasing demand through strengthened mental health literacy, as well as supply of available mental health services through strengthened detection and linkage to care.

OBJECTIVE: To assess the feasibility of a Community Mental Health Education and Detection Tool (CMED) for use with household members by community health teams in South Africa.

METHODS: The feasibility of using the CMED in households was assessed using Bowen et al.'s framework which informed the study design, interview tools and analysis. The feasibility study involved four phases: (1) observations of the CMED consultation to evaluate the administration of the tool; (2) semi-structured interviews with household member/s after the CMED was administered to explore experiences of the visit; (3) follow-up interviews of household members referred using the CMED tool to assess uptake of referrals; (4) and weekly focus group discussions with the community health team to explore experiences of using the tool. Framework analysis was used to inform a priori themes and allow inductive themes to emerge from the data.

RESULTS: The CMED was found to be acceptable by both community health teams and household members, demand for the tool was evident, implementation, practicality and integration within the existing health system were also indicated.

CONCLUSION: The CMED is perceived as feasible by household members and community health teams, suggesting a 'goodness of fit" within the existing health system.}, } @article {pmid38895485, year = {2024}, author = {Sikirzhytskaya, A and Tyagin, I and Sutton, SS and Wyatt, MD and Safro, I and Shtutman, M}, title = {AI-based mining of biomedical literature: Applications for drug repurposing for the treatment of dementia.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2024.06.06.597745}, pmid = {38895485}, issn = {2692-8205}, abstract = {UNLABELLED: Neurodegenerative pathologies such as Alzheimer's disease, Parkinson's disease, Huntington's disease, Amyotrophic lateral sclerosis, Multiple sclerosis, HIV-associated neurocognitive disorder, and others significantly affect individuals, their families, caregivers, and healthcare systems. While there are no cures yet, researchers worldwide are actively working on the development of novel treatments that have the potential to slow disease progression, alleviate symptoms, and ultimately improve the overall health of patients. Huge volumes of new scientific information necessitate new analytical approaches for meaningful hypothesis generation. To enable the automatic analysis of biomedical data we introduced AGATHA, an effective AI-based literature mining tool that can navigate massive scientific literature databases, such as PubMed. The overarching goal of this effort is to adapt AGATHA for drug repurposing by revealing hidden connections between FDA-approved medications and a health condition of interest. Our tool converts the abstracts of peer-reviewed papers from PubMed into multidimensional space where each gene and health condition are represented by specific metrics. We implemented advanced statistical analysis to reveal distinct clusters of scientific terms within the virtual space created using AGATHA-calculated parameters for selected health conditions and genes. Partial Least Squares Discriminant Analysis was employed for categorizing and predicting samples (122 diseases and 20889 genes) fitted to specific classes. Advanced statistics were employed to build a discrimination model and extract lists of genes specific to each disease class. Here we focus on drugs that can be repurposed for dementia treatment as an outcome of neurodegenerative diseases. Therefore, we determined dementia-associated genes statistically highly ranked in other disease classes. Additionally, we report a mechanism for detecting genes common to multiple health conditions. These sets of genes were classified based on their presence in biological pathways, aiding in selecting candidates and biological processes that are exploitable with drug repurposing.

AUTHOR SUMMARY: This manuscript outlines our project involving the application of AGATHA, an AI-based literature mining tool, to discover drugs with the potential for repurposing in the context of neurocognitive disorders. The primary objective is to identify connections between approved medications and specific health conditions through advanced statistical analysis, including techniques like Partial Least Squares Discriminant Analysis (PLSDA) and unsupervised clustering. The methodology involves grouping scientific terms related to different health conditions and genes, followed by building discrimination models to extract lists of disease-specific genes. These genes are then analyzed through pathway analysis to select candidates for drug repurposing.}, } @article {pmid38894894, year = {2024}, author = {Komatsu, T and Fraune, MR and Tsui, KM and Suda, S and Kobayashi, M}, title = {How did COVID-19 pandemic affect the older adults' needs for robot technologies in Japan?: comparison of participatory design workshops during versus after the COVID-19 pandemic.}, journal = {Frontiers in robotics and AI}, volume = {11}, number = {}, pages = {1363243}, pmid = {38894894}, issn = {2296-9144}, abstract = {Social technology can improve the quality of social lives of older adults (OAs) and mitigate negative mental and physical health outcomes. When people engage with technology, they can do so to stimulate social interaction (stimulation hypothesis) or disengage from their real world (disengagement hypothesis), according to Nowland et al.'s model of the relationship between social Internet use and loneliness. External events, such as large periods of social isolation like during the COVID-19 pandemic, can also affect whether people use technology in line with the stimulation or disengagement hypothesis. We examined how the COVID-19 pandemic affected the social challenges OAs faced and their expectations for robot technology to solve their challenges. We conducted two participatory design (PD) workshops with OAs during and after the COVID-19 pandemic. During the pandemic, OAs' primary concern was distanced communication with family members, with a prevalent desire to assist them through technology. They also wanted to share experiences socially, as such OA's attitude toward technology could be explained mostly by the stimulation hypothesis. However, after COVID-19 the pandemic, their focus shifted towards their own wellbeing. Social isolation and loneliness were already significant issues for OAs, and these were exacerbated by the COVID-19 pandemic. Therefore, such OAs' attitudes toward technology after the pandemic could be explained mostly by the disengagement hypothesis. This clearly reflect the OA's current situation that they have been getting further digitally excluded due to rapid technological development during the pandemic. Both during and after the pandemic, OAs found it important to have technologies that were easy to use, which would reduce their digital exclusion. After the pandemic, we found this especially in relation to newly developed technologies meant to help people keep at a distance. To effectively integrate these technologies and avoid excluding large parts of the population, society must address the social challenges faced by OAs.}, } @article {pmid38890057, year = {2025}, author = {Giommoni, L}, title = {The impact of precursor regulations on illicit drug markets: An analysis of Cunningham et al.'s studies.}, journal = {The International journal on drug policy}, volume = {138}, number = {}, pages = {104498}, doi = {10.1016/j.drugpo.2024.104498}, pmid = {38890057}, issn = {1873-4758}, mesh = {Humans ; *Illicit Drugs/economics/supply & distribution/legislation & jurisprudence ; *Drug and Narcotic Control/legislation & jurisprudence ; *Substance-Related Disorders/prevention & control/epidemiology/economics ; *Drug Trafficking/legislation & jurisprudence/economics ; *Commerce/legislation & jurisprudence ; }, abstract = {This review examines a series of twelve studies led by James K. Cunningham and his team, focusing on the effects of precursor regulation on illicit drug markets. Their research shows that the regulation of chemicals essential for the production of drugs such as heroin, cocaine, and methamphetamine is associated with several positive outcomes. These include a decrease in drug purity, a reduction in seizures, lower demand for treatment and hospitalization, and an increase in drug prices. According to the research, this decrease in harmful outcomes results from a combination of diminished overall consumption and a reduction in harm per dose. However, this review identifies some inconsistencies within their studies. These inconsistencies include premature assumptions about the timing of intervention impacts, uneven influences of similar interventions, variations in the implementation of these interventions, and the disregard of alternate explanations for sudden shifts in drug markets. Cunningham's work can be considered one of the most substantial contributions in this field. However, to secure the full confidence of the drug policy community in the authenticity of their findings, they must effectively address the issues identified in this review.}, } @article {pmid38890001, year = {2024}, author = {Pergent, M and Prevot, J and Solis, L and Farrugia, A}, title = {Immunoglobulin solutions for patients with primary immunodeficiency. Comments on Burnouf et al.'s 'Stepwise options for preparing therapeutic plasma proteins from domestic plasma in low- and middle-income countries'.}, journal = {Vox sanguinis}, volume = {119}, number = {9}, pages = {1021-1022}, doi = {10.1111/vox.13696}, pmid = {38890001}, issn = {1423-0410}, mesh = {Humans ; *Developing Countries ; Plasma ; Immunologic Deficiency Syndromes/therapy ; Immunoglobulins, Intravenous/therapeutic use ; }, } @article {pmid38889548, year = {2024}, author = {Balty, F and Baret, A and Silhanek, A and Nguyen, ND}, title = {Insight into the morphological instability of metallic nanowires under thermal stress.}, journal = {Journal of colloid and interface science}, volume = {673}, number = {}, pages = {574-582}, doi = {10.1016/j.jcis.2024.06.074}, pmid = {38889548}, issn = {1095-7103}, abstract = {HYPOTHESIS: Metallic nanowires, particularly polyol-grown silver nanowires, exhibit a morphological instability at temperatures significantly lower than their bulk melting point. This instability is commonly named after Rayleigh's description of the morphological instability of liquid jets, even though it has been shown that its quantitative predictions are not consistent with experimental measurements. In 1996, McCallum et al. proposed a description of the phenomenon assuming a solid wire lying on a substrate. It is assumed that the latter description depicts more accurately the reality.

EXPERIMENTS: Nanowires with varying diameters have been deposited on silicon wafers. Statistical analysis of their radius and the wavelength of their periodical instability have been performed.

FINDINGS: McCallum et al.'s model better aligns with experimental observations compared to Rayleigh's description. This validation provides a robust theoretical framework for enhancing the stability of nanowires, addressing a crucial aspect of their development.}, } @article {pmid38888358, year = {2024}, author = {Gewecke, A and Hare, RK and Salgård, C and Kyndi, L and Høg, M and Petersen, G and Nahimana, D and Abou-Chakra, N and Knudsen, JD and Rosendahl, S and Vissing, NH and Arendrup, MC}, title = {A single-source nosocomial outbreak of Aspergillus flavus uncovered by genotyping.}, journal = {Microbiology spectrum}, volume = {12}, number = {8}, pages = {e0027324}, pmid = {38888358}, issn = {2165-0497}, mesh = {*Aspergillus flavus/genetics/isolation & purification/classification ; Humans ; *Disease Outbreaks ; *Cross Infection/epidemiology/microbiology ; *Genotype ; *Aspergillosis/epidemiology/microbiology ; *Microsatellite Repeats ; Male ; Denmark/epidemiology ; Female ; Child ; Child, Preschool ; Mycological Typing Techniques/methods ; Adolescent ; }, abstract = {UNLABELLED: During construction work (2017-2019), an increase in Aspergillus flavus infections was noted among pediatric patients, the majority of whom were receiving amphotericin B prophylaxis. Microsatellite genotyping was used to characterize the outbreak. A total of 153 A. flavus isolates of clinical and environmental origin were included. Clinical isolates included 140 from 119 patients. Eight patients were outbreak-related patients, whereas 111 were outbreak-unrelated patients from Danish hospitals (1994-2023). We further included four control strains. Nine A. flavus isolates were from subsequent air sampling in the outbreak ward (2022-2023). Typing followed Rudramurthy et al.(S. M. Rudramurthy, H. A. de Valk, A. Chakrabarti, J. Meis, and C. H. W. Klaassen, PLoS One 6:e16086, 2011, https://doi.org/10.1371/journal.pone.0016086). Minimum spanning tree (MST) and discriminant analysis of principal components (DAPC) were used for cluster analysis. DAPC analysis placed all 153 isolates in five clusters. Microsatellite marker pattern was clearly distinct for one cluster compared to the others. The same cluster was observed in an MST. This cluster included all outbreak isolates, air-sample isolates, and additional patient isolates from the outbreak hospital, previously undisclosed as outbreak related. The highest air prevalence of A. flavus was found in two technical risers of the outbreak ward, which were then sealed. Follow-up air samples were negative for A. flavus. Microsatellite typing defined the outbreak as nosocomial and facilitated the identification of an in-hospital source. Six months of follow-up air sampling was without A. flavus. Outbreak-related/non-related isolates were easily distinguished with DAPC and MST, as the outbreak clone's distinct marker pattern was delineated in both statistical analyses. Thus, it could be a variant of A. flavus, with a niche ability to thrive in the outbreak-hospital environment.

IMPORTANCE: Aspergillus flavus can cause severe infections and hospital outbreaks in immunocompromised individuals. Although lack of isogeneity does not preclude an outbreak, our study underlines the value of microsatellite genotyping in the setting of potential A. flavus outbreaks. Microsatellite genotyping documented an isogenic hospital outbreak with an internal source. This provided the "smoking gun" that prompted the rapid allocation of resources for thorough environmental sampling, the results of which guided immediate and relevant cleaning and source control measures. Consequently, we advise that vulnerable patients should be protected from exposure and that genotyping be included early in potential A. flavus outbreak investigations. Inspection and sampling are recommended at any site where airborne spores might disperse from. This includes rarely accessed areas where air communication to the hospital ward cannot be disregarded.}, } @article {pmid38880485, year = {2024}, author = {Hill, RC and Zeldin, SD and Lipner, SR}, title = {Scarcity and imbalanced distribution of nail specialists in the United States: A cross-sectional study: Response to Shah et al.'s 'Analysis of Trends in US Dermatologist Density and Geographic Distribution'.}, journal = {Journal of the American Academy of Dermatology}, volume = {91}, number = {4}, pages = {e105-e106}, doi = {10.1016/j.jaad.2024.04.080}, pmid = {38880485}, issn = {1097-6787}, mesh = {United States ; Humans ; Cross-Sectional Studies ; *Dermatology/trends/statistics & numerical data ; *Dermatologists/statistics & numerical data/trends/supply & distribution ; *Nail Diseases/epidemiology ; Workforce/statistics & numerical data/trends ; }, } @article {pmid38867023, year = {2024}, author = {Gearin, B and Turtura, J and Anderson, K and Durrance, S and Mele-McCarthy, J and Schultz, L and Spitulnik, K}, title = {An interdisciplinary perspective on the strengths and weaknesses of the International Dyslexia Association definition of dyslexia.}, journal = {Annals of dyslexia}, volume = {74}, number = {3}, pages = {337-354}, pmid = {38867023}, issn = {1934-7243}, mesh = {Humans ; *Dyslexia/diagnosis/physiopathology ; Delphi Technique ; Terminology as Topic ; }, abstract = {This commentary article describes the results of a Delphi Method discussion between an interdisciplinary team of state dyslexia policy implementers. The authors argue that the International Dyslexia Association (IDA) definition of dyslexia from 2001 skews toward the perspectives of the research community, inadvertently creating implementation challenges for school practice. The article describes how the authors reached this determination; why they believe Vaughn et al.'s (Annals of Dyslexia, 2024) proposed definition marks an improvement over the 2001 IDA definition; and the need for continued support in the dyslexia policy implementation process, including knowledge dissemination efforts and updates to other relevant policy documents. This collaboration between policymakers, educators, and researchers contributes to the special issue by considering how the definition of dyslexia is situated in policy and practice. In so doing, it addresses a longstanding gap in academic research on how policy implementers understand and use the IDA definition.}, } @article {pmid38857818, year = {2024}, author = {Valentini, E and Halder, S and Romei, V}, title = {The independence and predictivity of resting pain-free slow alpha frequency as a biomarker of pain: A reply to Mazaheri et al.}, journal = {NeuroImage}, volume = {296}, number = {}, pages = {120681}, doi = {10.1016/j.neuroimage.2024.120681}, pmid = {38857818}, issn = {1095-9572}, mesh = {Humans ; *Alpha Rhythm/physiology ; *Biomarkers ; *Pain/physiopathology ; Pain Perception/physiology ; Electroencephalography/methods ; Bayes Theorem ; Brain/physiology ; }, abstract = {In response to Mazaheri et al.'s critique, we revisited our study (Valentini et al., 2022) on the relationship between peak alpha frequency (PAF) and pain. Their commentary prompted us to reassess our data to address the independence between slow and slowing alpha brain oscillations, as well as the predictivity of slow alpha oscillations in pain perception. Bayesian correlation analyses revealed mixed support for independence. Investigating predictivity, we found inconsistent associations between pre-PAF and unpleasantness ratings. We critically reflected on methodological and theoretical issues on the path to PAF validation as a pain biomarker. We emphasized the need for diversified methodology and analytical approaches as well as robust findings across research groups.}, } @article {pmid38856718, year = {2024}, author = {Luo, Y and Cao, K and Chiu, J and Chen, H and Wang, HJ and Thornton, ME and Grubbs, BH and Kolb, M and Parmacek, MS and Mishina, Y and Shi, W}, title = {Defective mesenchymal Bmpr1a-mediated BMP signaling causes congenital pulmonary cysts.}, journal = {eLife}, volume = {12}, number = {}, pages = {}, pmid = {38856718}, issn = {2050-084X}, support = {R01 HL141352/HL/NHLBI NIH HHS/United States ; R01 HL151699/HL/NHLBI NIH HHS/United States ; HL151699/HL/NHLBI NIH HHS/United States ; HL141352/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; *Bone Morphogenetic Protein Receptors, Type I/genetics/metabolism/deficiency ; *Signal Transduction ; Mice ; *Mice, Knockout ; *Lung/embryology/metabolism/pathology ; *Mesoderm/embryology/metabolism ; Cysts/metabolism/pathology/genetics ; Bone Morphogenetic Proteins/metabolism/genetics ; Lung Diseases/metabolism/pathology/genetics ; Disease Models, Animal ; }, abstract = {Abnormal lung development can cause congenital pulmonary cysts, the mechanisms of which remain largely unknown. Although the cystic lesions are believed to result directly from disrupted airway epithelial cell growth, the extent to which developmental defects in lung mesenchymal cells contribute to abnormal airway epithelial cell growth and subsequent cystic lesions has not been thoroughly examined. In the present study using genetic mouse models, we dissected the roles of bone morphogenetic protein (BMP) receptor 1a (Bmpr1a)-mediated BMP signaling in lung mesenchyme during prenatal lung development and discovered that abrogation of mesenchymal Bmpr1a disrupted normal lung branching morphogenesis, leading to the formation of prenatal pulmonary cystic lesions. Severe deficiency of airway smooth muscle cells and subepithelial elastin fibers were found in the cystic airways of the mesenchymal Bmpr1a knockout lungs. In addition, ectopic mesenchymal expression of BMP ligands and airway epithelial perturbation of the Sox2-Sox9 proximal-distal axis were detected in the mesenchymal Bmpr1a knockout lungs. However, deletion of Smad1/5, two major BMP signaling downstream effectors, from the lung mesenchyme did not phenocopy the cystic abnormalities observed in the mesenchymal Bmpr1a knockout lungs, suggesting that a Smad-independent mechanism contributes to prenatal pulmonary cystic lesions. These findings reveal for the first time the role of mesenchymal BMP signaling in lung development and a potential pathogenic mechanism underlying congenital pulmonary cysts.}, } @article {pmid38854079, year = {2024}, author = {Depuydt, L and Renders, L and de Vyver, SV and Veys, L and Gagie, T and Fostier, J}, title = {b-move: faster bidirectional character extensions in a run-length compressed index.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {38854079}, issn = {2692-8205}, support = {R01 HG011392/HG/NHGRI NIH HHS/United States ; }, abstract = {Due to the increasing availability of high-quality genome sequences, pan-genomes are gradually replacing single consensus reference genomes in many bioinformatics pipelines to better capture genetic diversity. Traditional bioinformatics tools using the FM-index face memory limitations with such large genome collections. Recent advancements in run-length compressed indices like Gagie et al.'s r-index and Nishimoto and Tabei's move structure, alleviate memory constraints but focus primarily on backward search for MEM-finding. Arakawa et al.'s br-index initiates complete approximate pattern matching using bidirectional search in run-length compressed space, but with significant computational overhead due to complex memory access patterns. We introduce b-move, a novel bidirectional extension of the move structure, enabling fast, cache-efficient bidirectional character extensions in run-length compressed space. It achieves bidirectional character extensions up to 8 times faster than the br-index, closing the performance gap with FM-index-based alternatives, while maintaining the br-index's favorable memory characteristics. For example, all available complete E. coli genomes on NCBI's RefSeq collection can be compiled into a b-move index that fits into the RAM of a typical laptop. Thus, b-move proves practical and scalable for pan-genome indexing and querying. We provide a C++ implementation of b-move, supporting efficient lossless approximate pattern matching including locate functionality, available at https://github.com/biointec/b-move under the AGPL-3.0 license.}, } @article {pmid38846619, year = {2024}, author = {Ravindranath, R and Sarma, PS and Sivasankaran, S and Thankappan, KR and Jeemon, P}, title = {Voices of care: unveiling patient journeys in primary care for hypertension and diabetes management in Kerala, India.}, journal = {Frontiers in public health}, volume = {12}, number = {}, pages = {1375227}, pmid = {38846619}, issn = {2296-2565}, mesh = {Humans ; *Hypertension/drug therapy/therapy ; *Primary Health Care/statistics & numerical data ; Male ; India ; Middle Aged ; Female ; *Qualitative Research ; *Diabetes Mellitus/therapy ; *Health Services Accessibility/statistics & numerical data ; Adult ; *Focus Groups ; Aged ; Interviews as Topic ; Patient Acceptance of Health Care/statistics & numerical data ; }, abstract = {BACKGROUND: Diabetes and hypertension are leading public health problems, particularly affecting low- and middle-income countries, with considerable variations in the care continuum between different age, socio-economic, and rural and urban groups. In this qualitative study, examining the factors affecting access to healthcare in Kerala, we aim to explore the healthcare-seeking pathways of people living with diabetes and hypertension.

METHODS: We conducted 20 semi-structured interviews and one focus group discussion (FGD) on a purposive sample of people living with diabetes and hypertension. Participants were recruited at four primary care facilities in Malappuram district of Kerala. Interviews were transcribed and analyzed deductively and inductively using thematic analysis underpinned by Levesque et al.'s framework.

RESULTS: The patient journey in managing diabetes and hypertension is complex, involving multiple entry and exit points within the healthcare system. Patients did not perceive Primary Health Centres (PHCs) as their initial points of access to healthcare, despite recognizing their value for specific services. Numerous social, cultural, economic, and health system determinants underpinned access to healthcare. These included limited patient knowledge of their condition, self-medication practices, lack of trust/support, high out-of-pocket expenditure, unavailability of medicines, physical distance to health facilities, and attitude of healthcare providers.

CONCLUSION: The study underscores the need to improve access to timely diagnosis, treatment, and ongoing care for diabetes and hypertension at the lower level of the healthcare system. Currently, primary healthcare services do not align with the "felt needs" of the community. Practical recommendations to address the social, cultural, economic, and health system determinants include enabling and empowering people with diabetes and hypertension and their families to engage in self-management, improving existing health information systems, ensuring the availability of diagnostics and first-line drug therapy for diabetes and hypertension, and encouraging the use of single-pill combination (SPC) medications to reduce pill burden. Ensuring equitable access to drugs may improve hypertension and diabetes control in most disadvantaged groups. Furthermore, a more comprehensive approach to healthcare policy that recognizes the interconnectedness of non-communicable diseases (NCDs) and their social determinants is essential.}, } @article {pmid38844709, year = {2024}, author = {Farooqi, HA and Nabi, R and Zahid, T and Hayder, Z}, title = {Breaking new ground: can artificial intelligence and machine learning transform papillary glioneuronal tumor diagnosis?.}, journal = {Neurosurgical review}, volume = {47}, number = {1}, pages = {261}, pmid = {38844709}, issn = {1437-2320}, mesh = {Humans ; *Artificial Intelligence ; *Brain Neoplasms/diagnosis/diagnostic imaging/pathology ; Glioma/diagnosis/diagnostic imaging/pathology ; *Machine Learning ; }, abstract = {Papillary glioneuronal tumors (PGNTs), classified as Grade I by the WHO in 2016, present diagnostic challenges due to their rarity and potential for malignancy. Xiaodan Du et al.'s recent study of 36 confirmed PGNT cases provides critical insights into their imaging characteristics, revealing frequent presentation with headaches, seizures, and mass effect symptoms, predominantly located in the supratentorial region near the lateral ventricles. Lesions often appeared as mixed cystic and solid masses with septations or as cystic masses with mural nodules. Given these complexities, artificial intelligence (AI) and machine learning (ML) offer promising advancements for PGNT diagnosis. Previous studies have demonstrated AI's efficacy in diagnosing various brain tumors, utilizing deep learning and advanced imaging techniques for rapid and accurate identification. Implementing AI in PGNT diagnosis involves assembling comprehensive datasets, preprocessing data, extracting relevant features, and iteratively training models for optimal performance. Despite AI's potential, medical professionals must validate AI predictions, ensuring they complement rather than replace clinical expertise. This integration of AI and ML into PGNT diagnostics could significantly enhance preoperative accuracy, ultimately improving patient outcomes through more precise and timely interventions.}, } @article {pmid38843612, year = {2024}, author = {Tan, YQ and Loh, CK and Mohd Saffian, S and Makpol, S}, title = {Improved HPLC method with automated pre-column sample derivatisation for serum pegylated L-asparaginase activity measurement in paediatric acute lymphoblastic leukaemia patients.}, journal = {Journal of pharmaceutical and biomedical analysis}, volume = {247}, number = {}, pages = {116243}, doi = {10.1016/j.jpba.2024.116243}, pmid = {38843612}, issn = {1873-264X}, mesh = {*Asparaginase/blood ; *Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy/blood ; Humans ; Chromatography, High Pressure Liquid/methods ; Child ; *Polyethylene Glycols/chemistry ; *Drug Monitoring/methods ; Antineoplastic Agents/blood ; Reproducibility of Results ; Chromatography, Reverse-Phase/methods ; Calibration ; }, abstract = {Therapeutic drug monitoring of pegylated L-asparaginase (ASNase) ensures the drug effectiveness in childhood acute lymphoblastic leukaemia (ALL) patients. The biological drug property with variable immunogenic host clearance, and the prescription of its generic formulation urge the need for a reliable assay to ensure an optimal treatment and improve outcome. This study aimed to optimise an existing isocratic reversed-phase high performance liquid chromatography (RP-HPLC) method with an automated pre-column sample derivatisation and injection program, and a computational algorithm for measuring serum pegylated ASNase activity in children with ALL. Nath et al.'s method in 2009 was adopted and modified using a pegylated ASNase. A set of Microsoft Excel macros was developed for the serum drug activity computation. An Agilent InfinityLab LC Series 1260 Infinity II Quaternary System with fluorescence detection was employed with an Agilent Poroshell 120 EC-C18 4.6×100 mm, 2.7 µm analytical column. System flow rate was optimised to 2.0 mL/min with 40×10[-6]/bar pump compressibility. The O-phthaldialdehyde (OPA) solution composition was optimised to 1 % o-phthaldialdehyde, 0.8 % 2-mercaptoethanol, 7.13 % methanol, and 1.81 % sodium tetraborate. The pre-column derivatisation program mixed 0.1 µL sample with 25 µL OPA solution before the automated injection. Method validation was according to the ICH guidelines. Total analysis time was 15 min, with L-aspartic acid eluted at 0.96 min and internal standard at 4.7 min. The calibration curves showed excellent linearity (R ≥0.9999). Interday precision for the drug activity at 0.1 IU/mL, 0.5 IU/mL, and 1 IU/mL were 4.15 %, 3.05 %, and 3.09 % (n = 6). Mean %error for the drug activity at 0.1 IU/mL, 0.5 IU/mL, and 1 IU/mL were 0.90±4.41 %, -1.37±3.04 %, and -3.03±3.02 % (n = 6). Limit of quantitation was 0.03 IU/mL. Majority of the patients' serum drug activity fell within the assay calibration range. Our improved method is automated, having shorter analysis time with a well-maintained separation resolution that enables a high-throughput analysis for application.}, } @article {pmid38840096, year = {2024}, author = {Sundareswaran, M and Martignetti, L and Purkey, E}, title = {Barriers to primary care among immigrants and refugees in Peterborough, Ontario: a qualitative study of provider perspectives.}, journal = {BMC primary care}, volume = {25}, number = {1}, pages = {199}, pmid = {38840096}, issn = {2731-4553}, mesh = {Humans ; Ontario ; *Refugees/statistics & numerical data ; *Health Services Accessibility ; *Primary Health Care ; *Qualitative Research ; *Emigrants and Immigrants/psychology ; *Focus Groups ; Female ; Male ; Adult ; Attitude of Health Personnel ; Middle Aged ; Social Stigma ; }, abstract = {BACKGROUND: Canada's immigrants and refugees have often settled in large Canadian cities, but this is changing with rising costs of living and rural settlement initiatives. However, little consideration is made regarding systemic changes needed to accommodate this distribution, particularly in healthcare in medium-sized cities or smaller communities. For most Canadians, primary care is an entry point into the healthcare system but immigrants and refugees face unique barriers to accessing care compared to the general Canadian population. This project aimed to better understand the barriers to accessing primary care among newcomers in Peterborough, Ontario from the perspective of newcomer service providers.

METHODOLOGY: Participants were recruited from community organizations identified by the local settlement agency, the New Canadians Centre, as having regular interactions with newcomer clients including clinics, not-for-profit organizations, and volunteer groups. Four focus groups were completed, each with three participants (n=12). A coding grid was deductively developed to guide thematic analysis by adapting Levesque et al.'s conceptual framework defining access to healthcare with five specific dimensions: approachability, acceptability, availability and accommodation, affordability, and appropriateness.

RESULTS: Participants identified lack of awareness of the healthcare system, stigma, competing priorities, and direct costs as some of the barriers for newcomers. Participants highlighted barriers unique to Peterborough including proximity to services, social isolation, and a shortage of family physicians. The results also highlighted strengths in the community such as its maternal-child health programming.

CONCLUSION: The results provide a glimpse of the challenges to accessing primary care among newcomers in medium-sized communities and identify opportunities to prepare for changing settlement patterns.}, } @article {pmid38839870, year = {2024}, author = {Ye, C and Li, H and Chen, Y and Hao, J and Liu, J and Shan, J and Qiao, SZ}, title = {The role of electrocatalytic materials for developing post-lithium metal||sulfur batteries.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {4797}, pmid = {38839870}, issn = {2041-1723}, abstract = {The exploration of post-Lithium (Li) metals, such as Sodium (Na), Potassium (K), Magnesium (Mg), Calcium (Ca), Aluminum (Al), and Zinc (Zn), for electrochemical energy storage has been driven by the limited availability of Li and the higher theoretical specific energies compared to the state-of-the-art Li-ion batteries. Post-Li metal||S batteries have emerged as a promising system for practical applications. Yet, the insufficient understanding of quantitative cell parameters and the mechanisms of sulfur electrocatalytic conversion hinder the advancement of these battery technologies. This perspective offers a comprehensive analysis of electrode parameters, including S mass loading, S content, electrolyte/S ratio, and negative/positive electrode capacity ratio, in establishing the specific energy (Wh kg[-1]) of post-Li metal||S batteries. Additionally, we critically evaluate the progress in investigating electrochemical sulfur conversion via homogeneous and heterogeneous electrocatalytic approaches in both non-aqueous Na/K/Mg/Ca/Al||S and aqueous Zn||S batteries. Lastly, we provide a critical outlook on potential research directions for designing practical post-Li metal||S batteries.}, } @article {pmid38839476, year = {2024}, author = {Pillai, RR and Sara, B}, title = {Effectiveness of bladder retraining programme on bedwetting frequency and relapse rate of children with nocturnal enuresis.}, journal = {Journal of pediatric urology}, volume = {20}, number = {4}, pages = {602.e1-602.e12}, doi = {10.1016/j.jpurol.2024.05.014}, pmid = {38839476}, issn = {1873-4898}, mesh = {Humans ; *Nocturnal Enuresis/therapy/epidemiology ; Child ; Male ; Female ; *Recurrence ; Surveys and Questionnaires ; Treatment Outcome ; India/epidemiology ; Urinary Bladder/physiopathology ; Adolescent ; Prevalence ; }, abstract = {BACKGROUND OF THE STUDY: Nocturnal enuresis, or bedwetting, is a prevalent and emotionally challenging condition that has a significant impact on the behavior, psychological well-being, and social lives of school-aged children.

AIM: This study aimed to assess the effectiveness of bladder retraining programme on bedwetting frequency and relapse rate among children with nocturnal enuresis.

METHODS: The study was conducted in two phases. The Phase I included a survey questionnaire to identify the prevalence of nocturnal enuresis among school children studying in Grade I to Grade X of 3 selected schools in Nashik, India. Out of 2150 prevalence questionnaires, 1900 filled in questionnaires were received back. 226 children were found to be positive for monosymptomatic nocturnal enuresis. A total of 160 children were selected from which 80 samples were included in experimental group and 80 were in control group. A three-step bladder retraining program was provided for parents and children in the experimental group. The parents and children from experimental group were called on the 15th day to reinforce the interventions. Posttests were conducted at 1st month (Posttest I), 3rd month (Posttest II), and 6th month (Posttest III/Relapse) for both experimental and control group.

RESULTS: The total prevalence of nocturnal enuresis among 1900 school age children aged 6 years-15 years is found to be 11.89%. Out of the 226 enuretic children, majority 101 (44.69%) wet their beds 1-3 times per week while 48 (21.23%) children wet their beds Every night. Comparison of bedwetting frequency in both groups during Pretest, Posttest I, Posttest II and Posttest III using chi-square test showed that: In pretest there was no significant difference between children in experimental and control group as indicated by the non-significant P value 0.43. Whereas in posttest I, II & III, P value 0.001 indicates highly significant difference in bedwetting frequency of children in both the groups. Children in experimental group had a relapse rate of 3.75% and 100% relapse was observed in control group during posttest III (at 6th month).

DISCUSSION: The study findings revealed a statistically significant reduction in bedwetting frequency within the experimental group (p = 0.001), contrasting with the control group's non-significant change (p = 0.17). Additionally, the relapse rate was markedly lower in the experimental group (3.75%) compared to the control group (100%). This aligns with Garcia-Fernandez and Petros' (2020) findings, where a squatting-based pelvic floor rehabilitation method demonstrated a significant reduction in bedwetting frequency, curing 86% of children. Van Kampen et al.'s (2009) study also supported the efficacy of pelvic floor muscle training in reducing relapse rates, providing further validation for the current study's findings.

CONCLUSION: The 3 step bladder retraining programme was found to be very effective in reducing the bedwetting frequency and relapse rate among children. This study provides evidence supporting effectiveness of such tailored bladder retraining interventions in managing monosymptomatic nocturnal enuresis in school-aged children.}, } @article {pmid38832742, year = {2024}, author = {Song, CX and Yan, ST and Godefroid, M and Bieroń, J and Jönsson, P and Gaigalas, G and Ekman, J and Zhang, XM and Chen, CY and Ning, CG and Si, R}, title = {Isotope shifts in electron affinities and in binding energies of Pb and hyperfine structure of 207Pb.}, journal = {The Journal of chemical physics}, volume = {160}, number = {21}, pages = {}, doi = {10.1063/5.0212299}, pmid = {38832742}, issn = {1089-7690}, abstract = {The isotope shifts in electron affinities of Pb were measured by Walter et al. [Phys. Rev. A 106, L010801 (2022)] to be -0.002(4) meV for 207-208Pb and -0.003(4) meV for 206-208Pb by scanning the threshold of the photodetachment channel Pb-(S3/2◦4) - Pb (3P0), while Chen and Ning reported 0.015(25) and -0.050(22) meV for the isotope shifts on the binding energies measured relative to 3P2 using the SEVI method [J. Chem. Phys. 145, 084303 (2016)]. Here we revisited these isotope shifts by using our second-generation SEVI spectrometer and obtained -0.001(15) meV for 207-208Pb and -0.001(14) meV for 206-208Pb, respectively. In order to aid the experiment by theory, we performed the first ab initio theoretical calculations of isotope shifts in electron affinities and binding energies of Pb, as well as the hyperfine structure of 207Pb-, by using the MCDHF and RCI methods. The isotope shifts in electron affinities of 207-208Pb and 206-208Pb are -0.0023(8) and -0.0037(13) meV for the 3P0 channel, respectively, in good agreement with Walter et al.'s measurements. The isotope shifts in binding energies relative to 3P1,2, -0.0015(8) and -0.0026(13) meV for 207-208Pb and 206-208Pb, respectively, are compatible with the present measurements. The hyperfine constant for the ground state of 207Pb- obtained by the present calculations, A(S3/2◦4)=-1118 MHz, differs by a factor of 3 from the previous estimation by Bresteau et al. [J. Phys. B: At., Mol. Opt. Phys. 52, 065001 (2019)]. The reliability is supported by the good agreement between the theoretical and experimental hyperfine parameters of 209Bi.}, } @article {pmid38832734, year = {2024}, author = {Kumar, R and Ghosh, A and Vaval, N}, title = {Relaxation of the 2a1 ionized water dimer: An interplay of intermolecular Coulombic decay (ICD) and proton transfer processes.}, journal = {The Journal of chemical physics}, volume = {160}, number = {21}, pages = {}, doi = {10.1063/5.0199888}, pmid = {38832734}, issn = {1089-7690}, abstract = {This article investigates the relaxation dynamics of the ionized 2a1 state of a water molecule within a water dimer. The study was motivated by findings from two previous pieces of research that focused on the relaxation behaviors of the inner-valence ionized water dimer. The present study discloses an observation indicating that water dimers display specific fragmentation patterns following inner-valence ionization, depending on the position of the vacancy. Vacancies were created in the 2a1 state of the proton-donating water molecule (PDWM) and proton-accepting water molecule (PAWM). Utilizing Born-Oppenheimer molecular dynamics simulations, the propagation of the 2a1 ionized state was carried out for both scenarios. The results revealed proton transfer occurred when the vacancy resided in the PDWM, accompanied by the closing of decay channels for O-H bond distance (RO-H) > 1.187 Å (matching Richter et al.'s findings). Conversely, when vacancy was on PAWM, we observed no closing of decay channels (aligning with Jahnke et al.'s findings). This difference translates to distinct fragmentation pathways. In PDWM cases, 2a1 state ionization leads to H3O+ -OH• formation. In contrast, PAWM vacancies result in decay pathways leading to H2O+-H2O+ products.}, } @article {pmid38829331, year = {2024}, author = {Beidas, RS and Saldana, L and Shelton, RC}, title = {Advancing a mission of translational intervention science: Comment on premature implementation.}, journal = {Journal of consulting and clinical psychology}, volume = {92}, number = {5}, pages = {324-326}, doi = {10.1037/ccp0000885}, pmid = {38829331}, issn = {1939-2117}, support = {UH3 DA050193/DA/NIDA NIH HHS/United States ; }, mesh = {Humans ; *Translational Research, Biomedical ; }, abstract = {Replies to comments made by Kenneth E. Freedland et al. (see record 2024-89430-002) on Rinad S. Beida, Lisa Saldana, and Rachel C. Shelton's original article (see record 2023-46817-001). In reading Freedland et al.'s (2024) commentary, it appears that their lens prioritizes internal validity and more explanatory and mechanistic work. While we also value these scientific goals and concur that the approaches they identify are clearly methodologically rigorous, we do not think the approaches will substantially reduce the unacceptable translation gap or address the fundamental issues of context. Our approach recognizes that there is tremendous value in cocreating solutions and interventions with patients, clinicians, and community members in the settings where we are seeking to promote health and address health inequities, and questions traditional assumptions and paradigms that scientists "know best" have effective solutions or should hold all of the power and knowledge (Brownson et al., 2022; Sanchez et al., 2023; Shelton, Adsul, & Oh, 2021; Shelton, Adsul, Oh, et al., 2021). We believe it is critical that we expand the pathways through which we advance intervention science in a meaningful and impactful way, and with more explicit attention to issues of context, equity, engagement, and external validity. (PsycInfo Database Record (c) 2024 APA, all rights reserved).}, } @article {pmid38821782, year = {2024}, author = {Ridley, AR and Speechley, EM}, title = {Problem-solving ability: a link between cognition and conservation?.}, journal = {Trends in ecology & evolution}, volume = {39}, number = {7}, pages = {609-611}, doi = {10.1016/j.tree.2024.05.010}, pmid = {38821782}, issn = {1872-8383}, mesh = {*Cognition ; *Conservation of Natural Resources ; *Problem Solving ; Animals ; }, abstract = {Traditionally, conservation and cognition have been disparate research disciplines. However, Audet et al.'s recent research contributes to an increasing body of evidence that innovative behaviours may determine the ability of species to respond to rapid environmental change, identifying an opportunity for cognition research to directly contribute to conservation outcomes.}, } @article {pmid38818588, year = {2024}, author = {Korchmaros, JD and Hall, K}, title = {Addressing Bioethical Implications of Implementing Diversion Programs in Resource-Constrained Service Environments.}, journal = {The Journal of law, medicine & ethics : a journal of the American Society of Law, Medicine & Ethics}, volume = {52}, number = {1}, pages = {76-79}, doi = {10.1017/jme.2024.53}, pmid = {38818588}, issn = {1748-720X}, mesh = {Humans ; Beneficence ; Bioethical Issues ; Opioid Epidemic/prevention & control ; Opioid-Related Disorders/prevention & control ; Personal Autonomy ; *Prescription Drug Diversion/prevention & control ; United States ; }, abstract = {The opioid epidemic demands the development, implementation, and evaluation of innovative, research-informed practices such as diversion programs. Aritürk et al. have articulated important bioethical considerations for implementing diversion programs in resource-constrained service environments. In this commentary, we expand and advance Aritürk et al.'s discussion by discussing existing resources that can be utilized to implement diversion programs that prevent or otherwise minimize the issues of autonomy, non-maleficence, beneficence, and justice identified by Aritürk et al.}, } @article {pmid38807700, year = {2024}, author = {Rodrigues, D and Rodrigues, N and Rebelo, T}, title = {Extending the understanding of the impact of conscientiousness on individual soccer performance: examining the mediating role of mental toughness.}, journal = {Current issues in personality psychology}, volume = {12}, number = {2}, pages = {140-151}, pmid = {38807700}, issn = {2353-561X}, abstract = {BACKGROUND: Drawing upon Motowidlo et al.'s theory of individual differences in individual performance, the current study aims to contribute to a better understanding of the relationship between conscientiousness and individual soccer performance, by examining whether mental toughness, posited as a characteristic adaptation, acts as a psychological mechanism underlying this link.

PARTICIPANTS AND PROCEDURE: Relying upon a concurrent validity design, 130 soccer players completed a survey including the measures of conscientiousness and mental toughness. Participants were also instructed to provide a subjective assessment of their individual soccer performance, by self-rating their physical, technical and tactical performance levels. Their objective performance was also measured as the total amount of minutes each player participated in official games, during the first half-season.

RESULTS: The findings showed that conscientiousness and mental toughness represent significant and meaningful predictors of both individual soccer performance measures gathered, i.e. individual soccer subjective and objective performance. As expected, further mediation analyses showed that the influence of conscientiousness on subjective performance is totally indirect, via mental toughness. Still, for the objective performance criterion, only the direct effect of conscientiousness was supported.

CONCLUSIONS: These findings support the merits of conscientiousness as a valid predictor of human performance across achievement contexts, namely in sports settings and specifically in the domain of soccer. They also suggest that while this personality factor exerts a direct impact on individual soccer objective performance, it seems to play a more distal influence on subjective performance, by enacting individual mental toughness resources. Major theoretical and applied research implications are discussed.}, } @article {pmid38801477, year = {2025}, author = {Parrillas-Manchón, S and Castroviejo, E and Hernández-Conde, JV and Rodríguez-Armendariz, E and Vicente, A}, title = {Testing the Labeling Effect in Autistic Children.}, journal = {Journal of autism and developmental disorders}, volume = {55}, number = {8}, pages = {2774-2787}, pmid = {38801477}, issn = {1573-3432}, support = {IT1537-22//Eusko Jaurlaritza/ ; PID2021-122233OB-I00 (FUNLAT)//Spanish Ministry of Science and Innovation and Spanish National Research Agency/ ; }, mesh = {Humans ; Male ; Child ; Female ; *Autistic Disorder/psychology ; *Concept Formation/physiology ; Child, Preschool ; }, abstract = {PURPOSE: Our objective was to test the labeling effect in autistic children. The effect has been robustly tested in typically developing (TD) individuals. TD children expect that any two objects that receive the same linguistic label will have similar properties, which suggests that they generate concepts based on acts of labeling. The labeling effect has not been tested on autistic children, who may not be equally attuned to the relevance of linguistic clues or may not generalize as swiftly as TD children.

METHODS: We reproduced Graham et al.,'s (Frontiers in Psychology 10.3389/fpsyg.2012.00586, 2013) design on 30 autistic children of different ages. Participants were divided into two groups depending on whether objects presented to them were named alike or differently (Same or Distinct Label between-individuals condition). The dependent variable was the number of target actions the child performed on an object, depending on whether that object made the same sound as a previously shown test object.

RESULTS: We did not reproduce results similar to those reported in Graham et al., (Frontiers in Psychology 10.3389/fpsyg.2012.00586, 2013). Children in the Same Label group did not perform significantly more actions than children in the Distinct Label group when the objects that were handed to the children did not make the same sound as the test object.

CONCLUSIONS: Autistic children do not seem to be sensitive to the labeling effect to the same extent as TD children. If these results are confirmed, intervention programs for autistic children should consider trainings on this way of generating concepts shared by their linguistic community.}, } @article {pmid38797132, year = {2024}, author = {Wakimoto, Y and Chen, Y and Honda, H and Shibahara, H}, title = {Advancements in the detection and implications of sperm-immobilizing antibodies in female infertility.}, journal = {Journal of reproductive immunology}, volume = {164}, number = {}, pages = {104256}, doi = {10.1016/j.jri.2024.104256}, pmid = {38797132}, issn = {1872-7603}, mesh = {Humans ; Female ; *Spermatozoa/immunology ; Male ; *Infertility, Female/immunology/therapy/diagnosis ; Pregnancy ; *Sperm Motility/immunology ; Autoantibodies/immunology ; Animals ; Fertilization in Vitro/methods ; Fertilization/immunology ; }, abstract = {This review highlights over five decades of research on sperm-immobilizing antibodies (SI-Abs), which are crucial for understanding female infertility due to their effects on sperm motility and fertilization. Since the 1960s, Isojima et al. have made significant strides, notably with the Sperm Immobilization Test (SIT), which revolutionized the quantification of SI-Abs and their roles in infertility. Drawing from a comprehensive PubMed search on "the sperm immobilization test" and "sperm immobilizing antibody," our review underscores the critical insights gained into SI-Abs' impact on reproductive functions. SI-Abs result from the body's response to sperm antigens, potentially leading to infertility by affecting post-intercourse sperm function. However, the presence of anti-sperm antibodies does not guarantee infertility, indicating a complex relationship between these antibodies and reproductive outcomes. Isojima et al.'s pioneering studies paved the way for SIT and sperm immobilization titer (SI50), tools that have clarified the link between SI-Abs and infertility, focusing on disrupted sperm mobility and fertilization as key infertility mechanisms. Clinically, interventions such as in-vitro fertilization (IVF), which bypasses or eliminates SI-Abs, have improved pregnancy rates, whereas Freund's complete adjuvant therapy has deepened our understanding of infertility mechanisms. The SI50 value is crucial for predicting fertility treatment success and guiding therapeutic decisions based on antibody levels. In summary, the evolution of SI-Abs research has provided new hope for addressing infertility, significantly enriching the field of reproductive immunology, and highlighting the need for ongoing investigation.}, } @article {pmid38790403, year = {2024}, author = {Samantaray, T and Anand, M and Saini, J and Gupta, CN}, title = {Introspection of UBNIN and Modified-UBNIN Algorithms for Structural MRI. Reply to Kelly et al. A Comparison of Brain-State Representations of Binary Neuroimaging Connectivity Data. Comment on "Samantaray et al. Unique Brain Network Identification Number for Parkinson's and Healthy Individuals Using Structural MRI. Brain Sci. 2023, 13, 1297".}, journal = {Brain sciences}, volume = {14}, number = {5}, pages = {}, pmid = {38790403}, issn = {2076-3425}, support = {Doctoral Scholarship//Ministry of Education (MoE), Government of India/ ; NEWGEN-IEDC//Department of Science and Technology, Government of India/ ; }, abstract = {The purpose of this reply is to address the comments given by Kelly et al. on our original paper "Unique Brain Network Identification Number for Parkinson's and Healthy Individuals using Structural MRI". We agree to the inadvertent rounding pitfall in our original paper due to the non-inclusion of symbolic math toolbox (MATLAB). We now provide the actual ranges (with decimal values) of the UBNIN values of healthy individuals and those with Parkinson's disease and further observations. Upon further introspection, we propose another variant, called Modified-UBNIN (UBNIN-MT,MN) which is highly weighted on the node with the highest network degree (i.e., connections). The italicized sentences within inverted commas are statements from Kelly et al.'s comment paper.}, } @article {pmid38780579, year = {2024}, author = {Oh, H and Sami, M and Bluthenthal, R and Huh, J}, title = {Racial discrimination and substance use among people of color.}, journal = {Psychology of addictive behaviors : journal of the Society of Psychologists in Addictive Behaviors}, volume = {38}, number = {4}, pages = {405-408}, pmid = {38780579}, issn = {1939-1501}, support = {R01 DA055839/DA/NIDA NIH HHS/United States ; }, mesh = {North American People ; Adolescent ; *Substance-Related Disorders/ethnology ; Black or African American ; *Racism/ethnology ; Racial Groups ; Humans ; Canada/epidemiology/ethnology ; }, abstract = {OBJECTIVE: We provide insights into studying racial discrimination and substance use among people of color, in response to Cénat et al.'s (2023) findings from Black youth in Canada.

METHOD: We discuss relevant literature on the topic.

RESULTS: Studying racial discrimination requires a dynamic and temporal conceptualization of race/racism within social contexts and an acknowledgment of the inadequacies of our current approaches. Further, studying the impact of racial discrimination may require an eclectic use of theories and the incorporation of community voices.

CONCLUSIONS: We recommend collecting measures of racism whenever possible, disaggregating race into ethnic groups and intersections of identities, engaging with communities to clarify concepts and select appropriate measures, and disseminating findings with opportunities for communities to speak and for researchers to listen. (PsycInfo Database Record (c) 2024 APA, all rights reserved).}, } @article {pmid38780277, year = {2025}, author = {Essex, R and Booth, L and Sirois, F and Burch, J and Dibley, L}, title = {A scoping review of the qualitative literature reporting experiences of living with a stoma for inflammatory bowel disease.}, journal = {Journal of advanced nursing}, volume = {81}, number = {1}, pages = {53-68}, pmid = {38780277}, issn = {1365-2648}, mesh = {Humans ; *Inflammatory Bowel Diseases/surgery/psychology ; *Surgical Stomas ; *Quality of Life/psychology ; *Qualitative Research ; *Adaptation, Psychological ; Cross-Sectional Studies ; Female ; Adult ; Male ; Middle Aged ; Aged ; }, abstract = {AIMS: Surgical treatment for inflammatory bowel disease (IBD) potentially includes stoma formation. Although positive clinical outcomes are widely reported, patients' responses to stoma surgery, including coming to terms with and adjusting to the stoma, vary widely. This scoping review charts the qualitative literature addressing the question: What is known about any personal psychosocial and quality of life factors that inform adjustment to living well with an intestinal stoma for IBD?

DESIGN: A scoping review methodology was employed.

DATA SOURCES: Searches of Scopus, Web of Science, CINAHL, Medline and PsycInfo in August 2023.

REVIEW METHODS: Levac et al.'s (2010) methodology was followed. PRISMA-ScR guidelines were adhered to.

RESULTS: Thirteen cross-sectional studies were included, involving a total of 142 participants. Four themes were identified: (1) facilitative factors; (2) barriers to adjustment; (3) personal attributes; and (4) time and temporality. Data indicate that personal and psychological factors influence adjustment, but not how this occurs. Adjustment takes longer to achieve than is conventionally (clinically) expected.

CONCLUSION: All available evidence is cross-sectional. The identified gap in the evidence is the notable lack of longitudinal research to assess, monitor and understand the complex process of adjustment in people with IBD having stoma-forming surgery. Detailed understanding of the process of adjustment would enable more targeted support for patients preparing for, and learning to live with, a stoma for IBD.

IMPACT: This paper highlights the need to understand the multiple personal and psychosocial factors that affect adjustment to life with a stoma and identifies that adjustment takes significantly longer than the few weeks required to become competent in managing the stoma.

Not applicable.}, } @article {pmid38778708, year = {2024}, author = {Peck, JL and Hettenhaus, K and King, K and Rigby, K}, title = {Empowering School Nurses: Enhancing Child Trafficking Awareness and Preparedness in American Public Schools.}, journal = {The Journal of school nursing : the official publication of the National Association of School Nurses}, volume = {40}, number = {6}, pages = {703-723}, doi = {10.1177/10598405241245955}, pmid = {38778708}, issn = {1546-8364}, mesh = {Humans ; *School Nursing/methods ; Child ; *Human Trafficking/prevention & control ; Oklahoma ; Schools ; Health Knowledge, Attitudes, Practice ; Female ; United States ; Male ; School Health Services/organization & administration ; }, abstract = {Child trafficking poses a momentous public health threat to students in public schools. Although school nurses are exceptionally positioned to identify and respond to trafficking, most lack training and resources in this critical area. This project aimed to evaluate the impact of a multifaceted intervention on school nurse preparedness and practices related to child trafficking in an Oklahoma public school district. The project involved Unbound Now's nationally accredited training program for school nurses, implementation of the Fuentes et al.'s Toolkit for Building a Human Trafficking School Safety Protocol (HTSSP) funded by the U.S. Department of Health and Human Services, and facilitation of a roundtable discussion to initiate community collaboration. The results of the pretraining Fraley and Aronowitz School Nurses' Awareness and Perceptions Survey (SNAPS) illuminated variations in school nurses' knowledge and awareness of child trafficking, demonstrating the need for continued training. Post-training evaluations exhibited highly positive feedback, suggesting its effectiveness in meeting the training's objectives. Following the community stakeholder roundtable, the lead school nurse employed the HTSSP toolkit and directed efforts in successfully constructing and implementing a district-wide policy of procedures to respond to suspected cases of human trafficking. However, the project's limitations include a small sample and a single-school district focus. Despite these limitations, this project delivers valuable insights into the challenges and opportunities for enhancing school nurse preparedness in addressing trafficking. This project serves as a foundation for future initiatives to improve students' safety and wellbeing in public schools.}, } @article {pmid38778316, year = {2024}, author = {Kukka, AJ and Bhattarai, P and Sundelin, HEK and Gurung, R and Brown, NJW and Litorp, H and Axelin, A and Kc, A}, title = {'We did everything by phone': a qualitative study of mothers' experience of smartphone-aided screening of cerebral palsy in Kathmandu, Nepal.}, journal = {BMC pediatrics}, volume = {24}, number = {1}, pages = {357}, pmid = {38778316}, issn = {1471-2431}, mesh = {Humans ; *Cerebral Palsy/diagnosis ; *Smartphone ; *Qualitative Research ; Female ; *Mothers/psychology ; Nepal ; *Focus Groups ; Infant, Newborn ; Adult ; *Mobile Applications ; Male ; }, abstract = {BACKGROUND: International guidelines recommend early intervention to all children at risk of cerebral palsy, but targeted screening programs are often lacking in low- and middle-income settings with the highest burden of disease. Smartphone applications have the potential to improve access to early diagnostics by empowering parents to film their children at home followed by centralized evaluation of videos with General Movements Assessment. We explored mothers' perceptions about participating in a smartphone aided cerebral palsy screening program in Kathmandu, Nepal.

METHODS: This is an explorative qualitative study that used focus group discussions (n = 2) and individual interviews (n = 4) with mothers of term-born infants surviving birth asphyxia or neonatal seizures. Parents used the NeuroMotion™ smartphone app to film their children at home and the videos were analysed using Precthl's General Movements Assessment. Sekhon et al.'s framework on the acceptability of health care interventions guided the design of the group discussions and interviews, and the deductive qualitative content analysis.

RESULTS: Mothers were interested in engaging with the programme and expressed hope it would benefit their children. Most felt using the app was intuitive. They were, however, unclear about the way the analysis was performed. Support from the research team was often needed to overcome an initial lack of self-confidence in using the technology, and to reduce anxiety related to the follow-up. The intervention was overall perceived as recommendable but should be supplemented by a face-to-face consultation.

CONCLUSION: Smartphone aided remote screening of cerebral palsy is acceptable in a lower middle-income population but requires additional technical support.}, } @article {pmid38775669, year = {2024}, author = {Guo, H and Tsige, M}, title = {Comment on "Effects of topological constraints on linked ring polymers in solvents of varying quality" by Z. A. Dehaghani, I. Chubak, C. N. Likos and M. R. Ejtehadi, Soft Matter, 2020, 16, 3029.}, journal = {Soft matter}, volume = {20}, number = {23}, pages = {4648-4650}, doi = {10.1039/d3sm01614e}, pmid = {38775669}, issn = {1744-6848}, abstract = {This comment critically evaluates the work of Dehaghani et al., who investigated the conformational behavior of catenated polymers under diverse solvent conditions using coarse-grained molecular dynamics simulations. While their study provides valuable insights into the scaling behavior of poly[n]catenane's radius of gyration in a good solvent, significant discrepancies arise, particularly concerning the reported θ-temperature trends. The validity of their methodology in determining θ-temperatures for linear and ring polymers is questioned, given observed disparities in chosen number of bead ranges that imply varying molecular weights. This comment underscores the need for a meticulous reassessment of the methodologies and interpretations presented in Dehaghani et al.'s study, emphasizing the importance of rigorous considerations in the investigation of the physical properties of catenated polymers.}, } @article {pmid38770870, year = {2024}, author = {Becker, S and Modirshanechi, A and Gerstner, W}, title = {Computational models of intrinsic motivation for curiosity and creativity.}, journal = {The Behavioral and brain sciences}, volume = {47}, number = {}, pages = {e94}, doi = {10.1017/S0140525X23003424}, pmid = {38770870}, issn = {1469-1825}, mesh = {*Creativity ; *Motivation ; Humans ; *Exploratory Behavior/physiology ; Models, Psychological ; Learning/physiology ; Memory/physiology ; Computer Simulation ; }, abstract = {We link Ivancovsky et al.'s novelty-seeking model (NSM) to computational models of intrinsically motivated behavior and learning. We argue that dissociating different forms of curiosity, creativity, and memory based on the involvement of distinct intrinsic motivations (e.g., surprise and novelty) is essential to empirically test the conceptual claims of the NSM.}, } @article {pmid38770858, year = {2024}, author = {Vaisarova, J and Lucca, K}, title = {A developmental account of curiosity and creativity.}, journal = {The Behavioral and brain sciences}, volume = {47}, number = {}, pages = {e116}, doi = {10.1017/S0140525X23003485}, pmid = {38770858}, issn = {1469-1825}, mesh = {*Creativity ; Humans ; *Exploratory Behavior/physiology ; Models, Psychological ; Human Development/physiology ; }, abstract = {Ivancovsky et al.'s Novelty-Seeking Model suggests several mechanisms that might underlie developmental change in creativity and curiosity. We discuss how these implications both do and do not align with extant developmental findings, suggest two further elements that can provide a more complete developmental account, and discuss current methodological barriers to formulating an integrated developmental model of curiosity and creativity.}, } @article {pmid38770848, year = {2024}, author = {Grüning, DJ and Krueger, JI}, title = {Toward a causal model of curiosity and creativity.}, journal = {The Behavioral and brain sciences}, volume = {47}, number = {}, pages = {e99}, doi = {10.1017/S0140525X23003382}, pmid = {38770848}, issn = {1469-1825}, mesh = {*Creativity ; Humans ; *Exploratory Behavior/physiology ; *Motivation ; *Models, Psychological ; Information Seeking Behavior ; }, abstract = {We extend Ivancovsky et al.'s finding on the association between curiosity and creativity by proposing a sequential causal model assuming that (a) curiosity determines the motivation to seek information and that (b) creativity constitutes a capacity to act on that motivation. This framework assumes that both high levels of curiosity and creativity are necessary for information-seeking behavior.}, } @article {pmid38759509, year = {2024}, author = {Pehlivan Sarıbudak, T and Üstün, B}, title = {Cancer patients' perceptions of nursing: Expectations & realities, a phenomenological study.}, journal = {European journal of oncology nursing : the official journal of European Oncology Nursing Society}, volume = {70}, number = {}, pages = {102603}, doi = {10.1016/j.ejon.2024.102603}, pmid = {38759509}, issn = {1532-2122}, mesh = {Humans ; Female ; Male ; *Neoplasms/psychology/nursing ; Middle Aged ; Adult ; *Qualitative Research ; *Nurse-Patient Relations ; Aged ; Oncology Nursing ; Patient Satisfaction ; Perception ; }, abstract = {PURPOSE: Determining the perception and expectations of cancer patients will inform nurses' understanding of how to conduct nursing care to meet patients' needs. Studies have mainly used quantitative methods to understand nursing image from the perspective of the public and the profession, and there are no recent studies to date on nursing image from the perspective of cancer patients. The aim of this qualitative study was to explore cancer patients' experiences and perceptions of nursing within the conceptual framework of Watson's Human Care Theory.

METHODS: In total, 19 phenomenological semi-structured interviews were conducted with cancer patients between November 2022 and January 2023. Data were analyzed using Assarroudi et al.'s content analysis.

RESULTS: Three themes emerged from the phenomenological analysis of the interviews: (1) nursing image, (2) expectations, and (3) realities. Patients stated that nurses act as assistants and that health services cannot be provided without them. Under the main theme of 'expectations,' five subthemes emerged: psychosocial care, physical care, ethics, individual characteristics, and no expectations, while the theme of 'realities' contained two subthemes: (1) satisfaction with nurse behaviors, and (2) dissatisfaction with nurse behaviors.

CONCLUSIONS: Our study provides important insight for nurses working with cancer patients in the management of patient care and treatment. Empowering cancer nurses will increase patient care satisfaction. We recommend the implementation of programs designed to support nurses and improve nursing communication skills. We also recommend that the technical and psychosocial aspects of nursing care should be considered as a whole.}, } @article {pmid38757496, year = {2024}, author = {Cihan, ÖF and Can, H and Yalçın, ED}, title = {Investigation of the relationship of the maxillary sinus floor with maxillary posterior teeth using cone beam CT.}, journal = {Folia morphologica}, volume = {83}, number = {4}, pages = {858-867}, doi = {10.5603/fm.99268}, pmid = {38757496}, issn = {1644-3284}, mesh = {Humans ; Male ; *Maxillary Sinus/diagnostic imaging/anatomy & histology ; Female ; Middle Aged ; *Cone-Beam Computed Tomography ; Adult ; Aged ; Adolescent ; Aged, 80 and over ; Young Adult ; *Molar/diagnostic imaging ; *Bicuspid/diagnostic imaging ; Retrospective Studies ; *Maxilla/diagnostic imaging ; }, abstract = {BACKGROUND: Any intervention to the maxillary posterior teeth (MPT) and alveola pose a risk of sinus perforation. Given the proximity of these structures, this study aimed to investigate the relationship between the maxillary sinus (MS) and MPT.

MATERIALS AND METHODS: CBCT images obtained from 207 patients (mean age, 45 ± 17 years; age range: 18-92 years) including 99 females and 108 males were examined retrospectively. Patients with sinus pathologies affecting the structure of MS and a history of oral and maxillofacial surgery were excluded from the study. On these images, the relationship of maxillary sinus floor (MSF) with 2 premolars and 3 molars was examined bilaterally for each patient using Kwak et al.'s classification. The presence, number, frequency and location of septa within the MSF were investigated.

RESULTS: Examination of a total of 410 maxillary sinuses on the images of 207 patients with no sinus perforation or pathology revealed that septa were most commonly (48.7%) located in the middle segment (second molars). When the relationship between the MSF and MPT was evaluated, molar teeth were found to have a closer relationship with the MSF than premolars.

CONCLUSIONS: It is believed that the findings of this study may provide further guidance to the dental practitioners and other clinicians for future studies.}, } @article {pmid38756563, year = {2024}, author = {Yousefi Afrashteh, M and Majzoobi, MR and Janjani, P and Forstmeier, S}, title = {The relationship between the meaning of life, psychological well-being, self-care, and social capital, with depression and death anxiety in the elderly living in nursing homes: The mediating role of loneliness.}, journal = {Heliyon}, volume = {10}, number = {9}, pages = {e30124}, pmid = {38756563}, issn = {2405-8440}, abstract = {The current study aims to investigate the meaning of life, psychological well-being, self-care, and social capital, with depression and death anxiety in the elderly living in nursing homes through the mediating role of loneliness. The statistical population included all the elderly aged at least 60 years living in Tehran, Qazvin and Zanjan, Iran in 2020, among whom 489 (273 men and 216 women) were selected using convenience sampling method. Participants filled out Steger's Meaning of Life, Ryff and Singer's Psychological Well-Being Scale, Söderhamn et al.'s Self-Care Ability, Nahapiet and Ghoshal's Social capital, Beck's depression, Templer's Death Anxiety, Russell et al.'s Loneliness questionnaires. The results indicated that meaning of life, psychological well-being, self-care, and social capital are negatively associated with loneliness, which in turn, is positively associated to depression. Furthermore, meaning of life, psychological well-being, self-care, and social capital are negatively associated with loneliness, which in turn, is positively associated to death anxiety. Moreover, the results of path analysis revealed that the hypothesized model of the current study has an excellent fit in the study sample. That is, meaning of life, psychological well-being, self-care, and social capital are related to depression and death anxiety through mediating role of loneliness.}, } @article {pmid38753426, year = {2024}, author = {Johnson, E and Sunil Kumar Sharma, R and Ruiz Cuenca, P and Byrne, I and Salgado-Lynn, M and Suraya Shahar, Z and Col Lin, L and Zulkifli, N and Dilaila Mohd Saidi, N and Drakeley, C and Matthiopoulos, J and Nelli, L and Fornace, K}, title = {Landscape drives zoonotic malaria prevalence in non-human primates.}, journal = {eLife}, volume = {12}, number = {}, pages = {}, pmid = {38753426}, issn = {2050-084X}, support = {/WT_/Wellcome Trust/United Kingdom ; 221963/Z/20/Z/WT_/Wellcome Trust/United Kingdom ; LRGS/1/2018/UM/01/1//Ministry of Higher Education Malaysia/ ; 221963/Z/20/Z//Royal Society/ ; }, mesh = {Animals ; Humans ; Asia, Southeastern/epidemiology ; Ecosystem ; *Malaria/epidemiology/transmission/parasitology ; *Plasmodium knowlesi ; Prevalence ; Primate Diseases/epidemiology/parasitology/transmission ; *Primates/parasitology ; *Zoonoses/epidemiology/parasitology/transmission ; }, abstract = {Zoonotic disease dynamics in wildlife hosts are rarely quantified at macroecological scales due to the lack of systematic surveys. Non-human primates (NHPs) host Plasmodium knowlesi, a zoonotic malaria of public health concern and the main barrier to malaria elimination in Southeast Asia. Understanding of regional P. knowlesi infection dynamics in wildlife is limited. Here, we systematically assemble reports of NHP P. knowlesi and investigate geographic determinants of prevalence in reservoir species. Meta-analysis of 6322 NHPs from 148 sites reveals that prevalence is heterogeneous across Southeast Asia, with low overall prevalence and high estimates for Malaysian Borneo. We find that regions exhibiting higher prevalence in NHPs overlap with human infection hotspots. In wildlife and humans, parasite transmission is linked to land conversion and fragmentation. By assembling remote sensing data and fitting statistical models to prevalence at multiple spatial scales, we identify novel relationships between P. knowlesi in NHPs and forest fragmentation. This suggests that higher prevalence may be contingent on habitat complexity, which would begin to explain observed geographic variation in parasite burden. These findings address critical gaps in understanding regional P. knowlesi epidemiology and indicate that prevalence in simian reservoirs may be a key spatial driver of human spillover risk.}, } @article {pmid38750390, year = {2024}, author = {Chan, YL and Tse, CS}, title = {Decoding the essence of two-character Chinese words: Unveiling valence, arousal, concreteness, familiarity, and imageability through word norming.}, journal = {Behavior research methods}, volume = {56}, number = {7}, pages = {7574-7601}, pmid = {38750390}, issn = {1554-3528}, mesh = {Humans ; *Arousal/physiology ; *Recognition, Psychology/physiology ; Female ; *Semantics ; Male ; Young Adult ; Adult ; Psycholinguistics/methods ; China ; Language ; }, abstract = {Investigation of affective and semantic dimensions of words is essential for studying word processing. In this study, we expanded Tse et al.'s (Behav Res Methods 49:1503-1519, 2017; Behav Res Methods 55:4382-4402, 2023) Chinese Lexicon Project by norming five word dimensions (valence, arousal, familiarity, concreteness, and imageability) for over 25,000 two-character Chinese words presented in traditional script. Through regression models that controlled for other variables, we examined the relationships among these dimensions. We included ambiguity, quantified by the standard deviation of the ratings of a given lexical variable across different raters, as separate variables (e.g., valence ambiguity) to explore their connections with other variables. The intensity-ambiguity relationships (i.e., between normed variables and their ambiguities, like valence with valence ambiguity) were also examined. In these analyses with a large pool of words and controlling for other lexical variables, we replicated the asymmetric U-shaped valence-arousal relationship, which was moderated by valence and arousal ambiguities. We also observed a curvilinear relationship between valence and familiarity and between valence and concreteness. Replicating Brainerd et al.'s (J Exp Psychol Gen 150:1476-1499, 2021; J Mem Lang 121:104286, 2021) quadratic intensity-ambiguity relationships, we found that the ambiguity of valence, arousal, concreteness, and imageability decreases as the value of these variables is extremely low or extremely high, although this was not generalized to familiarity. While concreteness and imageability were strongly correlated, they displayed different relationships with arousal, valence, familiarity, and valence ambiguity, suggesting their distinct conceptual nature. These findings further our understanding of the affective and semantic dimensions of two-character Chinese words. The normed values of all these variables can be accessed via https://osf.io/hwkv7 .}, } @article {pmid38746640, year = {2024}, author = {Jamshidi-Naeini, Y and Escobar Velasquez, N and Golzarri-Arroyo, L and Ali, S and Howard, LR and Dickinson, S and Allison, DB}, title = {Promoting Trustworthiness of Science: Reproducing and Verifying Agarwal et al.'s (2022) Findings Through Collaborative Endeavors.}, journal = {Journal of Alzheimer's disease reports}, volume = {8}, number = {1}, pages = {677-679}, pmid = {38746640}, issn = {2542-4823}, } @article {pmid38741125, year = {2024}, author = {Liu, L and Tang, Y and Baxter, GD and Yin, H and Tumilty, S}, title = {Responses to the correspondence from McDowell et al.'s on CAM integrative review of health care professionals in New Zealand.}, journal = {BMC complementary medicine and therapies}, volume = {24}, number = {1}, pages = {188}, pmid = {38741125}, issn = {2662-7671}, mesh = {New Zealand ; Humans ; *Complementary Therapies ; *Health Personnel ; Attitude of Health Personnel ; Health Knowledge, Attitudes, Practice ; }, abstract = {The authors of the manuscript 'Complementary and alternative medicine - practice, attitudes, and knowledge among healthcare professionals in New Zealand: an integrative review' [1] disagree with the assertion by McDowell et al. that our manuscript has extrapolation errors.}, } @article {pmid38741124, year = {2024}, author = {McDowell, JM and Kohut, SH and Betts, D}, title = {Extrapolation errors in Liu et al.'s CAM integrative review of health care professionals in New Zealand.}, journal = {BMC complementary medicine and therapies}, volume = {24}, number = {1}, pages = {187}, pmid = {38741124}, issn = {2662-7671}, mesh = {New Zealand ; Humans ; *Health Personnel ; *Complementary Therapies/statistics & numerical data ; Acupuncture Therapy ; Health Knowledge, Attitudes, Practice ; Attitude of Health Personnel ; }, abstract = {This letter is to highlight errors made by Liu et al. in their 2020 paper in BMC Complementary Medicine and Therapies, "Complementary and alternative medicine-practice, attitudes, and knowledge among healthcare professionals in New Zealand: an integrative review". Substantial errors in their citation of the recent research and methodology by McDowell, Kohut & Betts (2019) pertaining to the practice of acupuncture in New Zealand by physiotherapists are presented. The actual results of McDowell et al.'s work and the true state of acupuncture use by their sample group is reported.}, } @article {pmid38739430, year = {2024}, author = {Bell, RT and Sahakyan, H and Makarova, KS and Wolf, YI and Koonin, EV}, title = {CoCoNuTs are a diverse subclass of Type IV restriction systems predicted to target RNA.}, journal = {eLife}, volume = {13}, number = {}, pages = {}, pmid = {38739430}, issn = {2050-084X}, support = {Intramural Research Program/NH/NIH HHS/United States ; }, mesh = {*RNA, Bacterial/metabolism/chemistry/genetics ; Phylogeny ; Bacterial Proteins/metabolism/chemistry/genetics ; Bacteria/genetics/metabolism ; RNA/metabolism/genetics/chemistry ; }, abstract = {A comprehensive census of McrBC systems, among the most common forms of prokaryotic Type IV restriction systems, followed by phylogenetic analysis, reveals their enormous abundance in diverse prokaryotes and a plethora of genomic associations. We focus on a previously uncharacterized branch, which we denote coiled-coil nuclease tandems (CoCoNuTs) for their salient features: the presence of extensive coiled-coil structures and tandem nucleases. The CoCoNuTs alone show extraordinary variety, with three distinct types and multiple subtypes. All CoCoNuTs contain domains predicted to interact with translation system components, such as OB-folds resembling the SmpB protein that binds bacterial transfer-messenger RNA (tmRNA), YTH-like domains that might recognize methylated tmRNA, tRNA, or rRNA, and RNA-binding Hsp70 chaperone homologs, along with RNases, such as HEPN domains, all suggesting that the CoCoNuTs target RNA. Many CoCoNuTs might additionally target DNA, via McrC nuclease homologs. Additional restriction systems, such as Type I RM, BREX, and Druantia Type III, are frequently encoded in the same predicted superoperons. In many of these superoperons, CoCoNuTs are likely regulated by cyclic nucleotides, possibly, RNA fragments with cyclic termini, that bind associated CARF (CRISPR-Associated Rossmann Fold) domains. We hypothesize that the CoCoNuTs, together with the ancillary restriction factors, employ an echeloned defense strategy analogous to that of Type III CRISPR-Cas systems, in which an immune response eliminating virus DNA and/or RNA is launched first, but then, if it fails, an abortive infection response leading to PCD/dormancy via host RNA cleavage takes over.}, } @article {pmid38738680, year = {2024}, author = {Russell, I}, title = {Debate: More, not less social media content moderation? How to better protect youth mental health online.}, journal = {Child and adolescent mental health}, volume = {29}, number = {3}, pages = {319-321}, doi = {10.1111/camh.12717}, pmid = {38738680}, issn = {1475-357X}, mesh = {*Social Media ; Humans ; Adolescent ; Mental Health ; }, abstract = {BACKGROUND: This article challenges Zhang et al.'s claims that social media content moderation is proving detrimental to youth mental health and asserts that greater emphasis on the systemic risks posed by social media platforms is required.

METHOD: This commentary draws on my lived experience as a bereaved parent, empiricial evidence and ongoing public policy and regulatory debates.

CONCLUSIONS: Greater attention should be paid to the effects of algorithmic recommendation systems, which can result in teenagers becoming rapidly exposed to large amounts of harmful content on social media sites such as Instagram, Pinterest and TikTok.}, } @article {pmid38738356, year = {2024}, author = {Nonacs, P}, title = {The cost of success or failure for proxy signals in ecological problems.}, journal = {The Behavioral and brain sciences}, volume = {47}, number = {}, pages = {e79}, doi = {10.1017/S0140525X23002959}, pmid = {38738356}, issn = {1469-1825}, mesh = {Animals ; *Biological Evolution ; Marsupialia ; Humans ; }, abstract = {Two of John et al.'s examples of proxy failures in ecological situations are not failures: Runaway sexual selection and marsupial neonate competition. Instead, more appropriate ecological examples may be paternal genetic kin recognition and warning coloration. These differ in proxy effectiveness and failure in ways that illustrate the importance of "costs" in the evolution of ecological proxy traits.}, } @article {pmid38727799, year = {2025}, author = {Huddle, TS}, title = {On Seeing Long Shadows: Is Academic Medicine at its Core a Practice of Racial Oppression?.}, journal = {HEC forum : an interdisciplinary journal on hospitals' ethical and legal issues}, volume = {37}, number = {1}, pages = {107-125}, pmid = {38727799}, issn = {1572-8498}, mesh = {Humans ; *Racism/psychology ; Education, Medical/standards/methods ; United States ; *Systemic Racism ; }, abstract = {Suggestions that academic medicine is systemically racist are increasingly common in the medical literature. Such suggestions often rely upon expansive notions of systemic racism that are deeply controversial. The author argues for an empirical concept of systemic racism and offers a counter argument to a recent suggestion that academic medicine is systemically racist in its treatment of medical trainees: Anderson et al.'s (Academic Medicine, 98(8S), S28-S36, 2023) "The Long Shadow: a Historical Perspective on Racism in Medical Education." Contra the authors of "The Long Shadow," the author argues that racial performance disparities in medical education cannot be validly attributed to racism without careful empirical confirmation; he further argues that standards of assessment in medical education cannot be properly deemed racist merely because minority trainees are disproportionately disadvantaged by them. Furthermore, the history of medicine and society in the Anglo-European West is not, as argued by the authors of "The Long Shadow," best viewed as one long tale of racial oppression culminating in the present day pervasive racism of academic medicine in the United States. Racism is a deplorable stain on our history and our present but it is not the historical essence of Christianity, European civilization, Western medicine, or contemporary academic medical institutions.}, } @article {pmid38725362, year = {2024}, author = {Akhoundzadeh Yamchi, A and Sharifian, F and Khalife, E and Kaveh, M}, title = {Drying kinetic, thermodynamic and quality analyses of infrared drying of truffle slices.}, journal = {Journal of food science}, volume = {89}, number = {6}, pages = {3666-3686}, doi = {10.1111/1750-3841.17096}, pmid = {38725362}, issn = {1750-3841}, mesh = {*Thermodynamics ; Kinetics ; *Desiccation/methods ; *Food Handling/methods ; Infrared Rays ; Food Preservation/methods ; Temperature ; Water/chemistry ; }, abstract = {Kinetic and thermodynamic parameters are the most important part for making a suitable tool for drying agricultural products. Moreover, calculation of the energy required for the drying of product, the properties of the rehydration ratio, the food appearance changes, and the evaluation of the microstructure of food are crucial. Since the thermodynamic properties of truffle slices have not yet been reported, this study aims to establish a mathematical model to describe drying process of agriculture product, evaluate the effective moisture diffusion coefficient (Deff), determining the activation energy (Ea) to elucidate the thermodynamic characteristics, measure color characteristics, and rehydration ratio (RR) during the drying process of truffle slices. Truffle slices were dried in an infrared (IR) dryer at four temperatures of 50-80°C and two thicknesses of 0.5 and 1 cm. The best model to describe the drying process of truffle slices was Midilli et al.'s model. The value of Deff, SEC, and RR were in the range of 3.06 × 10[-8] to 2.48 × 10[-7] m[2]/s, 79.68-191.271 kWh/kg, and 5.99-7.49, respectively. The Deff of truffle slices increased with the above-mentioned parameters of the samples. The Ea obtained was 26.62-27.43 kJ/mol. The results indicated that enthalpy and entropy decreased with increasing drying temperature, while Gibbs free energy improved. The enthalpy, entropy, and Gibbs free energy values changed between 24.48-25.28 kJ/mol, -130.47 to -122.63 J/mol °K, and 63.97-70.17 kJ/mol, respectively. In addition, the results of color attributes decreased with increasing temperature, while chroma oppositely increased.}, } @article {pmid38724945, year = {2024}, author = {Li, X and Zhang, Y and Han, Y}, title = {The substitution effect of financial and non-financial incentives at different income levels in physician recruitment: evidence from medical students in China.}, journal = {BMC medical education}, volume = {24}, number = {1}, pages = {503}, pmid = {38724945}, issn = {1472-6920}, support = {72174129//National Natural Science Foundation of China/ ; }, mesh = {Humans ; *Students, Medical/psychology ; China ; *Motivation ; *Income ; *Altruism ; *Career Choice ; Female ; Male ; *Personnel Selection ; Adult ; Young Adult ; Physicians/psychology ; }, abstract = {BACKGROUND: Understanding how medical students respond to financial and non-financial incentives is crucial for recruiting health workers and attracting health talents in medical education. However, both incentives are integrated in working practice, and existing theoretical studies have suggested that various income levels may influence the substitution effect of both incentives, while the empirical evidence is lacking. Furthermore, little attention has been paid to the intrinsic motivation. This study aimed to explore the substitution effect of extrinsic incentives at different income levels, also taking intrinsic altruism into account.

METHODS: We used the behavioral data from Zhang et al.'s experiments, which involved discrete choice experiments (DCEs) to assess the job preferences of medical students from six teaching hospitals in Beijing, China. The incentive factors included monthly income, work location, work environment, training and career development opportunities, work load, and professional recognition. Additionally, a lab-like experiment in the medical decision-making context was conducted to quantify altruism based on utility function. Furthermore, we separated the choice sets based on the actual income and distinguished the medical students on altruism. The willingness to pay (WTP) was used to estimate the substitution effect of incentives through conditional logit model.

RESULTS: There was a significant substitution effect between non-financial and financial incentives. As income increased, non-financial incentives such as an excellent work environment, and sufficient career development became relatively more important. The impact of the increase in income on the substitution effect was more pronounced among individuals with higher altruism. Concerning the non-financial incentive work environment, in contrast to the growth of 546 CNY (84 USD) observed in the low-altruism group, the high-altruism group experienced a growth of 1040 CNY (160 USD) in the substitution effect.

CONCLUSIONS: The increase in the income level exerted an influence on the substitution effect of non-financial incentives and financial incentives, especially in high-altruism medical students. Policymakers should attach importance to a favorable environment and promising career prospects on the basis of ensuring a higher income level. Medical school administrations should focus on promoting altruistic values in medical education, enhancing talent incentives and teaching strategies to encourage medical students to devote themselves to the medical professions.}, } @article {pmid38722088, year = {2024}, author = {Zhong, X and Barnes, CR and Adamson-Macedo, EN and Li, X and Guo, X and He, T and Li, D and Li, Z and Wang, B and Wu, H}, title = {Psychometric testing of the Chinese version of the Perceived Maternal Parenting Self-Efficacy Scale among postpartum women.}, journal = {Child: care, health and development}, volume = {50}, number = {3}, pages = {e13267}, doi = {10.1111/cch.13267}, pmid = {38722088}, issn = {1365-2214}, support = {JKRWY23-19//Health Humanities Research Center, Key Research Base of Philosophy and Social Sciences, Zigong City/ ; 22007//Sichuan Hospital Association/ ; }, mesh = {Humans ; Female ; *Psychometrics ; Adult ; *Parenting/psychology ; *Self Efficacy ; *Postpartum Period/psychology ; Reproducibility of Results ; *Mothers/psychology ; China ; Surveys and Questionnaires/standards ; Young Adult ; Translations ; Depression, Postpartum/psychology/diagnosis ; }, abstract = {BACKGROUND: Maternal parenting self-efficacy plays a critical role in facilitating positive parenting practices and successful adaption to motherhood. The Perceived Maternal Parenting Self-Efficacy Scale (PMPS-E), as a task-specific measure, confirms its psychometric properties in cultural contexts. Compared with other tools, the advantages of the PMPS-E are as follows: (i) specific context or time period during the lifespan of a child, (ii) explicitly assess parenting self-efficacy across a diverse enough range of parenting tasks or activities during the perinatal/postnatal period and (iii) having robust psychometric properties. The aim of this study was to translate and determine the psychometric properties of the PMPS-E among Chinese postpartum women (C-PMPS-E).

METHOD: The cross-cultural adaptation process followed Beaton et al.'s intercultural debugging guidelines. A total of 471 women were included to establish the psychometric properties of the C-PMPS-E. Mothers were asked to complete the C-PMPS-E, Edinburgh Postnatal Depression Scale (EPDS), the Generalized Anxiety Disorder-7 (GAD-7) and several demographic questions. The psychometric testing of the C-PMPS-E was established through item analysis, construct validity and internal consistency reliability.

RESULTS: Item analysis showed that the critical ratios of all items were greater than 3 between the low-score group and high-score group, and all item-total correlation coefficients were greater than 0.4. The fit indices showed that the original correlated four-factor model of C-PMPS-E was observed to be an excellent fit to the data. The PMPS-E was negatively correlated with the EPDS and GAD-7 demonstrating its discriminant validity. As expected, no significant correlation was found between PMPS-E total or subscale scores and mothers' age. In addition, statistically significant differences for parity were detected for C-PMPS-E total and subscale scores with multipara having higher scores. This was taken as further evidence of the scale known-groups discriminant validity. In terms of internal consistency, the Cronbach's alpha of the C-PMPS-E total scale was 0.950, and subscales ranged from 0.76 to 0.89. Furthermore, a ROC curve analysis was conducted to establish the ability of the C-PMPS-E to distinguish between symptoms of depression and symptoms of anxiety. A cut-off value of 55 was identified that resulted in good specificity and fair sensitivity.

CONCLUSION: The C-PMPS-E is a reliable and valid tool to assess maternal parenting self-efficacy in a Chinese context.}, } @article {pmid38721953, year = {2024}, author = {Wang, J and Chen, X and Yuan, M}, title = {Bibliometric analysis of traditional Chinese medicine in the treatment of inflammatory bowel disease.}, journal = {Allergologia et immunopathologia}, volume = {52}, number = {3}, pages = {31-41}, pmid = {38721953}, issn = {1578-1267}, mesh = {*Bibliometrics ; Humans ; *Medicine, Chinese Traditional/methods ; *Inflammatory Bowel Diseases/drug therapy ; Drugs, Chinese Herbal/therapeutic use ; Animals ; }, abstract = {OBJECTIVE: This study conducts a bibliometric analysis of literature on the treatment of inflammatory bowel disease (IBD) with traditional Chinese medicine (TCM) to explore its research status, hotspots, and development trends, providing ideas and references for further research.

METHOD: We screened literature for treating IBD with TCM from the Web of Science Core Collection (WOSCC), and used the VOSviewer software (1.6.18) to discover cooperation among countries, institutions, authors, and information on journals, keywords, etc. We use the CiteSpace software (6.2.R2) to analyze co-citation and burst discovery of references.

RESULTS: In all, 440 relevant literature papers were searched and screened from the WOSCC database. The results showed that the number of publications concerning treating IBD with TCM has shown a significant growth in the past decade. China is far ahead in terms of article output, occupying a dominant position. The institution with the most published articles is Nanjing University of Traditional Chinese Medicine. The authors who have published most of the articles are Dai Yancheng, Shi Rui, and Zhou Lian. The Journal of Ethnopharmacology published maximum articles in this field, while Gastroenterology was the most cited journal. Ungaro et al.'s article entitled "Ulcerative colitis" (https://doi.org/10.1016/S0140-6736(16)32126-2), published in The Lancet in 2017 was the most cited study. The high-frequency keywords mainly include ulcerative colitis, inflammation, NF-κB, expression, traditional Chinese medicine, gut microbiota, activation, mice, cells, etc.

CONCLUSIONS: The research heat for treating IBD with TCM has risen over the past decade, with studies focusing on three main aspects: clinical studies of TCM, basic pharmacology, and animal experimental research. The research hotspot shifted from pathogenesis, clinical study of TCM, basic pharmacology, and complementary therapies to the study of network pharmacology and the mechanism of action of TCM related to gut microbiota. Network pharmacology and gut microbiota are at the frontiers of research and turning to be the future research trends to provide new insights and ideas for further research for treating IBD with TCM.}, } @article {pmid38717102, year = {2024}, author = {Goshtasbi, K and Tollefson, TT and Wong, BJ}, title = {Invited Commentary: Durairaj et al.'s "Artificial Intelligence vs. Expert Plastic Surgeon: Comparative Study Shows ChatGPT 'Wins' Rhinoplasty Consultations-Should We Be Worried?".}, journal = {Facial plastic surgery & aesthetic medicine}, volume = {26}, number = {3}, pages = {280-282}, doi = {10.1089/fpsam.2023.0310}, pmid = {38717102}, issn = {2689-3622}, mesh = {Humans ; *Rhinoplasty/methods ; *Artificial Intelligence ; Referral and Consultation ; Clinical Competence ; Surgery, Plastic ; }, } @article {pmid38715316, year = {2024}, author = {Smith, SK and Pryce, H and O'Connell, GB and Hussain, S and Shaw, R and Straus, J}, title = {'The burden is very much on yourself': A qualitative study to understand the illness and treatment burden of hearing loss across the life course.}, journal = {Health expectations : an international journal of public participation in health care and health policy}, volume = {27}, number = {3}, pages = {e14067}, pmid = {38715316}, issn = {1369-7625}, support = {131597//National Institute for Health and Care Research/ ; //University Hospitals Bristol/ ; //Weston NHS Foundation Trust/ ; }, mesh = {Humans ; *Qualitative Research ; Female ; Adult ; Middle Aged ; Male ; Aged ; *Hearing Loss/psychology/therapy ; *Cost of Illness ; *Adaptation, Psychological ; Aged, 80 and over ; Adolescent ; *Interviews as Topic ; Young Adult ; }, abstract = {INTRODUCTION: Hearing loss is a chronic health condition that rises sharply with age. The way people respond to and cope with health conditions is influenced by their capacity to perform illness and treatment-related work. The aim was to explore the cumulative burdens of living with hearing loss and the resources mobilised to ease the burdens.

METHODS: A qualitative design was used with semi-structured interviews (online or in-person) with participants recruited through audiology services and nonclinical services, such as lip-reading classes. Forty-six participants with hearing loss aged between 16 and 96 years were interviewed. An abductive approach, informed by May et al.'s burden of treatment theory, was used to analyse the data.

RESULTS: The illness burden involved participants working to make sense of their hearing loss, engaging in emotional work in response to changes in sound, social interactions and identity and coping with the daily frustrations required to communicate with others. Abandonment and uncertainty characterised the treatment burden; participants engaged in emotional work to adjust to hearing technology and deal with the uncertainty of how their hearing might progress. To ameliorate the burdens, participants drew on internal resources (psychological, health literacy, cognitive) and external resources (social support, financial, information, technology).

CONCLUSIONS: The workload of hearing loss appears largely devolved to the patient and is not always visible. Our work indicates the need to widen approaches in audiological care through the implementation of lifeworld-led care, family-centred care and peer support to build support for those with hearing loss.

We developed the project in consultation with members of the public who have lived experience of hearing loss recruited through Aston University and volunteer links to audiology services. We also consulted people more likely to be affected by hearing loss adults including adults with learning disabilities, older adults in residential care and people from South Asia (Bangladeshi, Indian and Pakistani communities). These individuals commented on the study aims, interview schedule and participant recruitment practices. One of our co-authors (expert by experience) contributed to the development and interpretation of themes and preparation of the final manuscript.}, } @article {pmid38715094, year = {2024}, author = {Nevedal, AL and Widerquist, MAO and Reardon, CM and Arasim, M and Jackson, GL and White, B and Burns, M and Fix, GM and DeLaughter, K and Cutrona, SL and Gifford, AL and Jasuja, GK and Hogan, TP and King, HA and Henderson, B and Damschroder, LJ}, title = {Understanding pathways from implementation to sustainment: a longitudinal, mixed methods analysis of promising practices implemented in the Veterans Health Administration.}, journal = {Implementation science : IS}, volume = {19}, number = {1}, pages = {34}, pmid = {38715094}, issn = {1748-5908}, mesh = {United States ; Humans ; *United States Department of Veterans Affairs/organization & administration ; Longitudinal Studies ; Implementation Science ; Diffusion of Innovation ; Program Evaluation ; Evidence-Based Practice/organization & administration ; COVID-19/epidemiology ; }, abstract = {BACKGROUND: The Veterans Health Administration (VHA) is the United States largest learning health system. The Diffusion of Excellence (DoE) program is a large-scale model of diffusion that identifies and diffuses evidence-informed practices across VHA. During the period of 2016-2021, 57 evidence-informed practices were implemented across 82 VHA facilities. This setting provides a unique opportunity to understand sustainment determinants and pathways. Our objective was to characterize the longitudinal pathways of practices as they transition from initial implementation to long-term sustainment at each facility.

METHODS: A longitudinal, mixed-methods evaluation of 82 VHA facilities. Eighty-two facility representatives, chosen by leadership as points-of-contact for 57 DoE practices, were eligible for post-implementation interviews and annual sustainment surveys. Primary outcomes (implementation, sustainment), and secondary outcomes (institutionalization, effectiveness, anticipated sustainment) at four time-points were collected. We performed descriptive statistics and directed content analysis using Hailemariam et al.'s factors influencing sustainment.

RESULTS: After approximately five years post-implementation (e.g., 2021 sustainment outcomes), of the 82 facilities, about one-third fully sustained their practice compared to one-third that did not fully sustain their practice because it was in a "liminal" stage (neither sustained nor discontinued) or permanently discontinued. The remaining one-third of facilities had missing 2021 sustainment outcomes. A higher percentage of facilities (70%) had inconsistent primary outcomes (changing over time) compared to facilities (30%) with consistent primary outcomes (same over time). Thirty-four percent of facilities with sustained practices reported resilience since they overcame implementation and sustainment barriers. Facilities with sustained practices reported more positive secondary outcomes compared to those that did not sustain their practice. Key factors facilitating practice sustainment included: demonstrating practice effectiveness/benefit, sufficient organizational leadership, sufficient workforce, and adaptation/alignment with local context. Key factors hindering practice sustainment included: insufficient workforce, not able to maintain practice fidelity/integrity, critical incidents related to the COVID-19 pandemic, organizational leadership did not support sustainment of practice, and no ongoing support.

CONCLUSIONS: We identified diverse pathways from implementation to sustainment, and our data underscore that initial implementation outcomes may not determine long-term sustainment outcomes. This longitudinal evaluation contributes to understanding impacts of the DoE program, including return on investment, achieving learning health system goals, and insights into achieving high-quality healthcare in VHA.}, } @article {pmid38713446, year = {2024}, author = {Dai, X and Liao, W and Xu, F and Lu, W and Xi, X and Fang, X and Wu, Q}, title = {External validation of predictive models for new vertebral fractures following percutaneous vertebroplasty.}, journal = {European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society}, volume = {}, number = {}, pages = {}, pmid = {38713446}, issn = {1432-0932}, support = {220602184532348//Shaoguan City Science and Technology Bureau Shaoguan City Social Development Science and Technology Collaborative Innovation System Construction Project/ ; }, abstract = {OBJECTIVE: To investigate the external validation and scalability of four predictive models regarding new vertebral fractures following percutaneous vertebroplasty.

METHODS: Utilizing retrospective data acquired from two centers, compute the area under the curve (AUC), calibration curve, and Kaplan-Meier plot to assess the model's discrimination and calibration.

RESULTS: In the external validation of Zhong et al.'s 2015 predictive model for the probability of new fractures post-vertebroplasty, the AUC for re-fracture at 1, 2, and 3 years postoperatively was 0.570, 0.617, and 0.664, respectively. The AUC for Zhong et al.'s 2016 predictive model for the probability of new fractures in neighboring vertebrae was 0.738. Kaplan-Meier plot results for both models indicated a significantly lower incidence of re-fracture in low-risk patients compared to high-risk patients. Li et al.'s 2021 model had an AUC of 0.518, and its calibration curve suggested an overestimation of the probability of new fractures. Li et al.'s 2022 model had an AUC of 0.556, and its calibration curve suggested an underestimation of the probability of new fractures.

CONCLUSION: The external validation of four models demonstrated that the predictive model proposed by Zhong et al. in 2016 exhibited superior external generalization capabilities.}, } @article {pmid38703337, year = {2024}, author = {Idnay, B and Cordoba, E and Ramirez, SO and Xiao, E and Wood, OR and Batey, DS and Garofalo, R and Schnall, R}, title = {Social Marketing Perspective on Participant Recruitment in Informatics-Based Intervention Studies.}, journal = {AIDS and behavior}, volume = {28}, number = {9}, pages = {2836-2849}, pmid = {38703337}, issn = {1573-3254}, support = {U01 MD011279/MD/NIMHD NIH HHS/United States ; T15 LM007079/LM/NLM NIH HHS/United States ; K24 NR018621/NR/NINR NIH HHS/United States ; R01NR019758/NR/NINR NIH HHS/United States ; P30 NR016587/NR/NINR NIH HHS/United States ; P30NR016587/NR/NINR NIH HHS/United States ; T32 NR007969/NR/NINR NIH HHS/United States ; R01 NR019758/NR/NINR NIH HHS/United States ; R01MH118151/MH/NIMH NIH HHS/United States ; T15LM007079//U.S. National Library of Medicine/ ; K24NR018621/NR/NINR NIH HHS/United States ; T32NR007969/NR/NINR NIH HHS/United States ; R01 MH118151/MH/NIMH NIH HHS/United States ; R36HS028752//Agency for Healthcare Research and Quality/ ; U01MD011279/MD/NIMHD NIH HHS/United States ; R01 HS025071/HS/AHRQ HHS/United States ; R36 HS028752/HS/AHRQ HHS/United States ; R01HS025071//Agency for Healthcare Research and Quality/ ; }, mesh = {Humans ; Male ; *Social Marketing ; Female ; *Qualitative Research ; Adult ; *Patient Selection ; *HIV Infections/psychology ; Middle Aged ; Interviews as Topic ; Motivation ; Decision Making ; }, abstract = {Effective recruitment strategies are pivotal for informatics-based intervention trials success, particularly for people living with HIV (PLWH), where engagement can be challenging. Although informatics interventions are recognized for improving health outcomes, the effectiveness of their recruitment strategies remains unclear. We investigated the application of a social marketing framework in navigating the nuances of recruitment for informatics-based intervention trials for PLWH by examining participant experiences and perceptions. We used qualitative descriptive methodology to conduct semi-structured interviews with 90 research participants from four informatics-based intervention trials. Directed inductive and deductive content analyses were guided by Howcutt et al.'s social marketing framework on applying the decision-making process to research recruitment. The majority were male (86.7%), living in the Northeast United States (56%), and identified as Black (32%) or White (32%). Most participants (60%) completed the interview remotely. Sixteen subthemes emerged from five themes: motivation, perception, attitude formation, integration, and learning. Findings from our interview data suggest that concepts from Howcutt et al.'s framework informed participants' decisions to participate in an informatics-based intervention trial. We found that the participants' perceptions of trust in the research process were integral to the participants across the four trials. However, the recruitment approach and communication medium preferences varied between older and younger age groups. Social marketing framework can provide insight into improving the research recruitment process. Future work should delve into the complex interplay between the type of informatics-based interventions, trust in the research process, and communication preferences, and how these factors collectively influence participants' willingness to engage.}, } @article {pmid38702707, year = {2024}, author = {Pouresmail, Z and Heshmati Nabavi, F and Rassouli, M}, title = {Quality of services in health education nurse-led clinics: an Iranian service providers and service recipients experience.}, journal = {BMC health services research}, volume = {24}, number = {1}, pages = {581}, pmid = {38702707}, issn = {1472-6963}, support = {980401//Fatemeh Heshmati Nabavi/ ; }, mesh = {Humans ; Iran ; *Qualitative Research ; *Quality of Health Care ; Male ; Female ; Adult ; Practice Patterns, Nurses' ; Middle Aged ; Health Education ; }, abstract = {BACKGROUND: Patient education is a vital role of nurses in nurse-led clinics(NLCs). Since 2011, independent NLCs entitled health education Nurse-led clinics(HENLCs) have been established in Iran. In order for this newly developed service to be able to perform perfectly in implementation and evaluation, it should be explained based on one of the quality evaluation models. The objective of the study was to determine the dimension of service quality in HENLCs based on service providers' and service recipients' experience.

METHODS: This research is a qualitative study of directed content analysis type conducted between May and November 2020. Twenty-nine participants who had rich experiences in the patient education in HENLCs were interviewed in this study. Asarroodi et al.'s (2018) qualitative content analysis method was used for data analysis, and MaxQDA software was used for data management. We used credibility, dependability, and Confirmability to confirm the trustworthiness of the study's findings.

RESULTS: In this study service providers including managers, policymakers, decision-makers, nurses, physicians, and service recipients including patients and families participated. Seven generic categories, including (1) a competent and self-motivated nurse educator, (2) an easily accessible and comfortable environment, (3) informational-educational materials and health education equipment, (4) motivational facilities, (5) access to the health education support team, (6) organizational communication supporting the education process, and (7) receiving the patient education fee, constituted the main category of structure. Five generic categories, including (1) assessment and determination of the educational needs of the target group, (2) description of the nurse's duties, (3) teaching-learning methods, (4) patient referral, and (5) the process of preparing and publishing educational content, constituted the main category of process. One generic category called evaluation constituted the main category of outcome.

CONCLUSION: Based on the results of this study, it is suggested to managers to pay attention to the dimensions of the quality model of Donabedian (SPO) in setting up and developing the performance of HENLCs, it is recommended that future quantitative studies based on the categories formed in this study evaluate the observance of the dimensions of structure, process and outcome.}, } @article {pmid38695821, year = {2024}, author = {Refaeli, T and Achdut, N}, title = {Ethnocultural disparities in loneliness among women in Israel: A population-based study.}, journal = {The American journal of orthopsychiatry}, volume = {94}, number = {6}, pages = {692-704}, doi = {10.1037/ort0000755}, pmid = {38695821}, issn = {1939-0025}, mesh = {Humans ; *Loneliness/psychology ; Israel/ethnology ; Female ; *Arabs/statistics & numerical data/psychology ; *Jews/statistics & numerical data/psychology ; Adult ; *Emigrants and Immigrants/psychology/statistics & numerical data ; Cross-Sectional Studies ; Middle Aged ; USSR/ethnology ; Socioeconomic Factors ; Risk Factors ; Residence Characteristics/statistics & numerical data ; Young Adult ; }, abstract = {Loneliness was predicted for women in three ethnocultural groups in Israel: native Jews, Israeli Arabs, and Former Soviet Union (FSU) immigrants. The study was based on Lund et al.'s (2018) conceptualization of social determinant domains of mental health disorders, as in the United Nations Sustainable Development Goals. Social determinants were demographic, economic, social-cultural, and neighborhood factors. We examined whether ethnocultural disparities in loneliness persist when controlling for social determinants in these four domains or whether ethnic disparities are related to other forms of inequality among the three study groups, as reflected in these four domains. Next, we explored associations between the co-occurrence of key social determinants with loneliness. We used cross-sectional representative data of working-age women from the Israeli Social Survey (N = 5,600). Hierarchical logistic regression analyses indicated a higher risk for loneliness among FSU immigrants and Israeli Arabs than among native Jews. Economic risk factors significantly increased the risk of loneliness. Social and cultural factors decreased the risk of loneliness, while discrimination increased it. Improved neighborhood conditions decreased the risk of loneliness. Ethnocultural disparities in loneliness diminished when economic determinants were controlled. Co-occurrence of risk factors greatly increased the risk for loneliness, demonstrating a stepped relationship. Developing supportive networks for women, mainly from minority groups, to increase trust and fight discrimination against any background is necessary. Moreover, significant efforts must be made to combat poverty and narrow socioeconomic inequalities. (PsycInfo Database Record (c) 2024 APA, all rights reserved).}, } @article {pmid38690007, year = {2024}, author = {Kanmodi, KK and Amzat, J and Aminu, K}, title = {Theories, determinants, and intervention models and approaches on inequalities of undernutrition amongst under fives: A literature review.}, journal = {Health science reports}, volume = {7}, number = {5}, pages = {e2078}, pmid = {38690007}, issn = {2398-8835}, abstract = {BACKGROUND AND AIMS: One of the greatest public health problems of the 21st century is undernutrition in children under the age of 5 years (CAUFY). Globally, over 232 million CUAFY are undernourished and approximately 45% of mortality in this population are undernutrition-induced. This paper reviewed and critically explained the factors perpetuating undernutrition in CUAFY in the global space. It further explained the multi-level determinants that influence health inequalities and consequently exacerbate undernutrition amongst CUAFY globally. It also went further to explain the intervention models and approaches that can be used to tackle undernutrition in CUAFY.

Demiris et al.'s approach to narrative review was utilized for this paper. Relevant articles on child nutrition were retrieved from multiple credible databases and websites of foremost health organizations. Using an iterative process, multiple combinations of search terms were done by stringing relevant key terms and their synonyms with Boolean Operators. This process was constantly refined to align search results with the study aim. Database search produced relevant and resourceful publications which were utilized to develop this review.

RESULTS: The global burden of undernutrition remains high, especially in Oceania with the highest prevalence of stunting and wasting (41.4% and 12.5%), with Africa and Asia following closely. Malnutrition eradication is a global health issue of high priority as demonstrated by the "Goal 2" of the Sustainable Development Goals (SDGs), and the United Nations (UN) Decade of Action on Nutrition 2016-2025. The review identified no significant positive outcome from previous interventions due to the endemic health inequalities. Determinants of the multi-level health inequalities associated with undernutrition in CUAFY, and probable solutions are explained with theoretical models of health inequalities. A diagonal intervention approach was proposed as a viable solution to ending undernutrition in CUAFY.

CONCLUSION: The application of relevant theoretical models and context-specific intervention approaches can be utilized by stakeholders to close the existing inequality gaps, thereby reducing undernutrition amongst CUAFY globally.}, } @article {pmid38687997, year = {2024}, author = {Freestone, J and Noble, WS and Keich, U}, title = {Reinvestigating the Correctness of Decoy-Based False Discovery Rate Control in Proteomics Tandem Mass Spectrometry.}, journal = {Journal of proteome research}, volume = {23}, number = {6}, pages = {1907-1914}, doi = {10.1021/acs.jproteome.3c00902}, pmid = {38687997}, issn = {1535-3907}, mesh = {*Tandem Mass Spectrometry/methods ; *Proteomics/methods ; *Databases, Protein ; *Protein Processing, Post-Translational ; Peptides/analysis/chemistry ; Machine Learning ; Humans ; Algorithms ; Software ; }, abstract = {Traditional database search methods for the analysis of bottom-up proteomics tandem mass spectrometry (MS/MS) data are limited in their ability to detect peptides with post-translational modifications (PTMs). Recently, "open modification" database search strategies, in which the requirement that the mass of the database peptide closely matches the observed precursor mass is relaxed, have become popular as ways to find a wider variety of types of PTMs. Indeed, in one study, Kong et al. reported that the open modification search tool MSFragger can achieve higher statistical power to detect peptides than a traditional "narrow window" database search. We investigated this claim empirically and, in the process, uncovered a potential general problem with false discovery rate (FDR) control in the machine learning postprocessors Percolator and PeptideProphet. This problem might have contributed to Kong et al.'s report that their empirical results suggest that false discovery (FDR) control in the narrow window setting might generally be compromised. Indeed, reanalyzing the same data while using a more standard form of target-decoy competition-based FDR control, we found that, after accounting for chimeric spectra as well as for the inherent difference in the number of candidates in open and narrow searches, the data does not provide sufficient evidence that FDR control in proteomics MS/MS database search is inherently problematic.}, } @article {pmid38687302, year = {2024}, author = {Walker, F and Whiteing, N and Aggar, C}, title = {Exploring clinical facilitation and student learning on undergraduate nursing placements through a community of practice lens: A qualitative study.}, journal = {Contemporary nurse}, volume = {60}, number = {2}, pages = {192-207}, doi = {10.1080/10376178.2024.2347874}, pmid = {38687302}, issn = {1839-3535}, mesh = {Humans ; *Education, Nursing, Baccalaureate/methods ; *Qualitative Research ; New South Wales ; *Students, Nursing/psychology ; Female ; Adult ; Male ; Middle Aged ; Clinical Competence ; Learning ; Community of Practice ; }, abstract = {Background: High-quality clinical placement experiences are important for preparing undergraduate student nurses for practice. Clinical facilitation and support significantly impact student placement experiences and their development of skills, knowledge, and attitudes in the healthcare setting.Aim: This research aimed to explore university-employed clinical facilitators' perspectives on providing quality clinical facilitation and student learning on placement.Design: An exploratory, descriptive research design was used to examine the perspectives of n = 10 university-employed clinical facilitators working in regional New South Wales, Australia (March 2020-December 2021).Methods: Semi-structured interviews were used to explore the experiences of a purposeful sample of university-employed clinical facilitators. Data was thematically analysed using Miles et al.'s (2014) qualitative data analysis framework.Results: Five key themes were identified 1) relationships at the core of quality, 2) a culture of commitment to student learning, 3) connection to the curriculum, 4) examining the model, and 5) empowering growth and development. Clinical facilitators perceive their role as misunderstood, undervalued, and isolating and that they require further preparation and ongoing professional development to provide quality facilitation. Building rapport and relationships with staff and students was at the core of quality clinical facilitation.Conclusions: The clinical facilitator role has an important function in preparing student nurses for practice and needs further recognition and continued professional development. Education providers and healthcare organisations need to examine strategies to provide inclusive and supportive work environments, building communities of practice for clinical facilitators and stakeholders to share their experiences and knowledge, promoting individual and group learning, thus improving the student placement experience and fostering the professional identity of clinical facilitators.}, } @article {pmid38677177, year = {2024}, author = {Lin, X and Wang, R and Chen, J}, title = {The reliability and validity of the brief measures of perceived childhood harshness and unpredictability: A revised Chinese version for emerging adults.}, journal = {Child abuse & neglect}, volume = {153}, number = {}, pages = {106810}, doi = {10.1016/j.chiabu.2024.106810}, pmid = {38677177}, issn = {1873-7757}, mesh = {Humans ; Male ; Female ; Reproducibility of Results ; *Psychometrics ; Young Adult ; China ; Adolescent ; Surveys and Questionnaires/standards ; Factor Analysis, Statistical ; Adult ; Child ; Child Abuse/psychology ; Translations ; Students/psychology ; }, abstract = {BACKGROUND: Childhood harshness and unpredictability significantly shape life history strategies, as well as downstream psychological and behavioral patterns. However, prior research involving Chinese populations has suffered from inconsistent metrics and limited measurement items.

OBJECTIVE: We adapted the English version of Maranges et al.'s (2022) Harshness and Unpredictability Scale in Childhood, translating it into Chinese and assessing its reliability and validity.

PARTICIPANTS AND SETTING: Six groups of different college student samples have been collected and the Chinese version of the Harshness and Unpredictability scales has been revised in two separate studies.

METHODS: We evaluated the factor structure using both exploratory and confirmatory factor analyses, determined internal consistency, item discrimination, concurrent validity, and assessed gender measurement invariance through multiple CFAs. The test-retest reliability was subsequently established by assessing participants after a designated interval.

RESULTS: Both scales passed psychometric tests, including exploratory and confirmatory factor analyses, and exhibited strong internal consistency and item discrimination. Gender invariance in the measurements was also confirmed.

CONCLUSIONS: The Chinese version of the Childhood Harshness and Unpredictability Scale demonstrates high reliability and validity, making it suitable for deeper examinations into the relationship between early environments and life history strategies in Chinese contexts.}, } @article {pmid38676932, year = {2024}, author = {Oppegaard, KR and Mayo, SJ and Armstrong, TS and Dokiparthi, V and Melisko, M and Levine, JD and Olshen, AB and Anguera, JA and Roy, R and Paul, S and Cooper, B and Conley, YP and Hammer, MJ and Miaskowski, C and Kober, KM}, title = {Neurodegenerative disease pathways are perturbed in patients with cancer who self-report cognitive changes and anxiety: A pathway impact analysis.}, journal = {Cancer}, volume = {130}, number = {16}, pages = {2834-2847}, doi = {10.1002/cncr.35336}, pmid = {38676932}, issn = {1097-0142}, support = {T32NR016920/NR/NINR NIH HHS/United States ; CA134900/CA/NCI NIH HHS/United States ; CA233774/CA/NCI NIH HHS/United States ; CA082103/CA/NCI NIH HHS/United States ; //International Society of Nurses in Genetics/ ; //Sigma Theta Tau International Honor Society of Nursing-Alpha Eta Chapter/ ; T32NR016920/NR/NINR NIH HHS/United States ; 5U54CA156734-12//University of Massachusetts Boston-Dana-Farber/Harvard Cancer Center U54 Comprehensive Partnership for Cancer Health Disparities Research/ ; //Leavitt PhD Student Scholarship/ ; CA134900/CA/NCI NIH HHS/United States ; CA233774/CA/NCI NIH HHS/United States ; CA082103/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; Female ; Male ; *Anxiety ; Middle Aged ; *Neoplasms/psychology/complications ; *Neurodegenerative Diseases/psychology ; *Self Report ; Aged ; Signal Transduction ; Cognitive Dysfunction/etiology ; Adult ; }, abstract = {BACKGROUND: Cancer-related cognitive impairment (CRCI) and anxiety co-occur in patients with cancer. Little is known about mechanisms for the co-occurrence of these two symptoms. The purposes of this secondary analysis were to evaluate for perturbed pathways associated with the co-occurrence of self-reported CRCI and anxiety in patients with low versus high levels of these two symptoms and to identify potential mechanisms for the co-occurrence of CRCI and anxiety using biological processes common across any perturbed neurodegenerative disease pathways.

METHODS: Patients completed the Attentional Function Index and the Spielberger State-Trait Anxiety Inventory six times over two cycles of chemotherapy. Based on findings from a previous latent profile analysis, patients were grouped into none versus both high levels of these symptoms. Gene expression was quantified, and pathway impact analyses were performed. Signaling pathways for evaluation were defined with the Kyoto Encyclopedia of Genes and Genomes database.

RESULTS: A total of 451 patients had data available for analysis. Approximately 85.0% of patients were in the none class and 15.0% were in the both high class. Pathway impact analyses identified five perturbed pathways related to neurodegenerative diseases (i.e., amyotrophic lateral sclerosis, Huntington disease, Parkinson disease, prion disease, and pathways of neurodegeneration-multiple diseases). Apoptosis, mitochondrial dysfunction, oxidative stress, and endoplasmic reticulum stress were common biological processes across these pathways.

CONCLUSIONS: This study is the first to describe perturbations in neurodegenerative disease pathways associated with CRCI and anxiety in patients receiving chemotherapy. These findings provide new insights into potential targets for the development of mechanistically based interventions.}, } @article {pmid38671345, year = {2024}, author = {Kwok, VK and Reid, N and Hubbard, RE and Thavarajah, H and Gordon, EH}, title = {Multicomponent perioperative interventions to improve outcomes for frail patients: a systematic review.}, journal = {BMC geriatrics}, volume = {24}, number = {1}, pages = {376}, pmid = {38671345}, issn = {1471-2318}, mesh = {Humans ; *Perioperative Care/methods ; Aged ; *Frail Elderly ; Postoperative Complications/prevention & control/epidemiology ; Frailty ; Aged, 80 and over ; Treatment Outcome ; }, abstract = {BACKGROUND: Preoperative frailty is associated with increased risk of adverse outcomes. In 2017, McIsaac and colleagues' systematic review found that few interventions improved outcomes in this population and evidence was low-quality. We aimed to systematically review the evidence for multicomponent perioperative interventions in frail patients that has emerged since McIsaac et al.'s review.

METHODS: PUBMED, EMBASE, Cochrane, and CINAHL databases were searched for English-language studies published since January 1, 2016, that evaluated multicomponent perioperative interventions in patients identified as frail. Quality was assessed using the National Institute of Health Quality Assessment Tool. A narrative synthesis of the extracted data was conducted.

RESULTS: Of 2835 articles screened, five studies were included, all of which were conducted in elective oncologic gastrointestinal surgical populations. Four hundred and thirteen patients were included across the five studies and the mean/median age ranged from 70.1 to 87.0 years. Multicomponent interventions were all applied in the preoperative period. Two studies also applied interventions postoperatively. All interventions addressed exercise and nutritional domains with variability in timing, delivery, and adherence. Multicomponent interventions were associated with reduced postoperative complications, functional deterioration, length of stay, and mortality. Four studies reported on patient-centred outcomes. The quality of evidence was fair.

CONCLUSIONS: This systematic review provides evidence that frail surgical patients undergoing elective oncologic gastrointestinal surgery may benefit from targeted multicomponent perioperative interventions. Yet methodological issues and substantial heterogeneity of the interventions precludes drawing clear conclusions regarding the optimal model of care. Larger, low risk of bias studies are needed to evaluate optimal intervention delivery, effectiveness in other populations, implementation in health care settings and ascertain outcomes of importance for frail patients and their carers.}, } @article {pmid38666562, year = {2024}, author = {Lin, YH and Pan, PY and Wu, CT}, title = {Interlinking circadian rhythms with urological health and blood pressure fluctuations: Insights from Kato Y et al.'s study on nocturnal polyuria in men with LUTS.}, journal = {International journal of urology : official journal of the Japanese Urological Association}, volume = {31}, number = {8}, pages = {948-949}, doi = {10.1111/iju.15481}, pmid = {38666562}, issn = {1442-2042}, mesh = {Humans ; Male ; *Circadian Rhythm/physiology ; *Blood Pressure/physiology ; *Lower Urinary Tract Symptoms/physiopathology/etiology ; *Polyuria/physiopathology ; Nocturia/physiopathology ; }, } @article {pmid38661440, year = {2024}, author = {Tate, K and Cummings, G and Jacobsen, F and Halas, G and Van den Bergh, G and Devkota, R and Shrestha, S and Doupe, M}, title = {Strategies to Improve Emergency Transitions From Long-Term Care Facilities: A Scoping Review.}, journal = {The Gerontologist}, volume = {64}, number = {7}, pages = {}, pmid = {38661440}, issn = {1758-5341}, support = {//Norges Forskningsråd/ ; }, mesh = {Humans ; Aged ; *Emergency Service, Hospital ; *Long-Term Care/standards/organization & administration ; *Patient Transfer/standards ; Homes for the Aged/standards/organization & administration ; Aged, 80 and over ; Quality Improvement ; }, abstract = {BACKGROUND AND OBJECTIVES: Older adults residing in residential aged care facilities (RACFs) often experience substandard transitions to emergency departments (EDs) through rationed and delayed ED care. We aimed to identify research describing interventions to improve transitions from RACFs to EDs.

RESEARCH DESIGN AND METHODS: In our scoping review, we included English language articles that (a) examined an intervention to improve transitions from RACF to EDs; and (b) focused on older adults (≥65 years). We employed content analysis. Dy et al.'s Care Transitions Framework was used to assess the contextualization of interventions and measurement of implementation success.

RESULTS: Interventions in 28 studies included geriatric assessment or outreach services (n = 7), standardized documentation forms (n = 6), models of care to improve transitions from RACFs to EDs (n = 6), telehealth services (n = 3), nurse-led care coordination programs (n = 2), acute-care geriatric departments (n = 2), an extended paramedicine program (n = 1), and a web-based referral system (n = 1). Many studies (n = 17) did not define what "improvement" entailed and instead assessed documentation strategies and distal outcomes (e.g., hospital admission rates, length of stay). Few authors reported how they contextualized interventions to align with care environments and/or evaluated implementation success. Few studies included clinician perspectives and no study examined resident- or family/friend caregiver-reported outcomes.

DISCUSSION AND IMPLICATIONS: Mixed or nonsignificant results prevent us from recommending (or discouraging) any interventions. Given the complexity of these transitions and the need to create sustainable improvement strategies, future research should describe strategies used to embed innovations in care contexts and to measure both implementation and intervention success.}, } @article {pmid38652785, year = {2024}, author = {Jussim, L}, title = {Diversity Is Diverse: Social Justice Reparations and Science.}, journal = {Perspectives on psychological science : a journal of the Association for Psychological Science}, volume = {19}, number = {3}, pages = {564-575}, doi = {10.1177/17456916241236171}, pmid = {38652785}, issn = {1745-6924}, mesh = {*Social Justice ; Humans ; *Cultural Diversity ; Psychology ; }, abstract = {Because the term "diversity" has two related but different meanings, what authors mean when they use the term is inherently unclear. In its broad form, it refers to vast variety. In its narrow form, it refers to human demographic categories deemed deserving of special attention by social justice-oriented activists. In this article, I review Hommel's critique of Roberts et al. (2020), which, I suggest, essentially constitutes two claims: that Roberts et al.'s (2020) call for diversity in psychological science focuses exclusively on the latter narrow form of diversity and ignores the scientific importance of diversity in the broader sense, and ignoring diversity in the broader sense is scientifically unjustified. Although Hommel's critique is mostly justified, this is not because Roberts et al. (2020) are wrong to call for greater social justice-oriented demographic diversity in psychology but because Hommel's call for the broader form of diversity subsumes that of Roberts et al. (2020) and has other aspects critical to creating a valid, generalizable, rigorous, and inclusive psychological science. In doing so, I also highlight omissions, limitations, and potential downsides to the narrow manner in which psychology and the broader academy are currently implementing diversity, equity, and inclusion.}, } @article {pmid38647728, year = {2024}, author = {Diamand, R and Roche, JB and Lacetera, V and Simone, G and Windisch, O and Benamran, D and Fourcade, A and Fournier, G and Fiard, G and Ploussard, G and Roumeguère, T and Peltier, A and Albisinni, S}, title = {Predicting contralateral extraprostatic extension in unilateral high-risk prostate cancer: a multicentric external validation study.}, journal = {World journal of urology}, volume = {42}, number = {1}, pages = {247}, pmid = {38647728}, issn = {1433-8726}, mesh = {Humans ; Male ; *Prostatic Neoplasms/pathology/surgery ; Aged ; Middle Aged ; Risk Assessment ; *Prostatectomy/methods ; Retrospective Studies ; Neoplasm Invasiveness ; Algorithms ; Extranodal Extension ; Prostate/pathology ; }, abstract = {PURPOSE: Accurate prediction of extraprostatic extension (EPE) is crucial for decision-making in radical prostatectomy (RP), especially in nerve-sparing strategies. Martini et al. introduced a three-tier algorithm for predicting contralateral EPE in unilateral high-risk prostate cancer (PCa). The aim of the study is to externally validate this model in a multicentric European cohort of patients.

METHODS: The data from 208 unilateral high-risk PCa patients diagnosed through magnetic resonance imaging (MRI)-targeted and systematic biopsies, treated with RP between January 2016 and November 2021 at eight referral centers were collected. The evaluation of model performance involved measures such as discrimination (AUC), calibration, and decision-curve analysis (DCA) following TRIPOD guidelines. In addition, a comparison was made with two established multivariable logistic regression models predicting the risk of side specific EPE for assessment purposes.

RESULTS: Overall, 38%, 48%, and 14% of patients were categorized as low, intermediate, and high-risk groups according to Martini et al.'s model, respectively. At final pathology, EPE on the contralateral prostatic lobe occurred in 6.3%, 12%, and 34% of patients in the respective risk groups. The algorithm demonstrated acceptable discrimination (AUC 0.68), comparable to other multivariable logistic regression models (p = 0.3), adequate calibration and the highest net benefit in DCA. The limitations include the modest sample size, retrospective design, and lack of central revision.

CONCLUSION: Our findings endorse the algorithm's commendable performance, supporting its utility in guiding treatment decisions for unilateral high-risk PCa patients.}, } @article {pmid38644404, year = {2024}, author = {Szczygieł, M and Sarı, MH}, title = {The relationship between numerical magnitude processing and math anxiety, and their joint effect on adult math performance, varied by indicators of numerical tasks.}, journal = {Cognitive processing}, volume = {25}, number = {3}, pages = {421-442}, pmid = {38644404}, issn = {1612-4790}, support = {BN.610-104/PBU/2020//Uniwersytet Pedagogiczny im. Komisji Edukacji Narodowej w Krakowie/ ; }, mesh = {Humans ; Female ; Male ; Young Adult ; *Anxiety/physiopathology/psychology ; *Reaction Time/physiology ; *Mathematics ; Adult ; *Problem Solving/physiology ; Adolescent ; Mathematical Concepts ; Neuropsychological Tests ; }, abstract = {According to the hypothesis of Maloney et al. (Cognition 114(2):293-297, 2010. https://doi.org/10.1016/j.cognition.2009.09.013), math anxiety is related to deficits in numerical magnitude processing, which in turn compromises the development of advanced math skills. Because previous studies on this topic are contradictory, which may be due to methodological differences in the measurement of numerical magnitude processing, we tested Maloney et al.'s hypothesis using different tasks and their indicators: numerical magnitude processing (symbolic and non-symbolic comparison tasks: accuracy, reaction time, numerical ratio, distance and size effects, and Weber fraction; number line estimation task: estimation error), math anxiety (combined scores of learning, testing, math problem solving, and general math anxiety), and math performance. The results of our study conducted on 119 young adults mostly support the hypothesis proposed by Maloney et al. that deficiency in symbolic magnitude processing is related to math anxiety, but the relationship between non-symbolic processes and math anxiety was opposite to the assumptions. Moreover, the results indicate that estimation processes (but not comparison processes) and math anxiety are related to math performance in adults. Finally, high math anxiety moderated the relationship between reaction time in the symbolic comparison task, reaction time in the non-symbolic comparison task, numerical ratio effect in the symbolic comparison task, and math performance. Because the results of the joint effect of numerical magnitude processing and math anxiety on math performance were inconsistent, this part of the hypothesis is called into question.}, } @article {pmid38635204, year = {2024}, author = {Javalagi, AA and Newman, DA and Li, M}, title = {Personality and leadership: Meta-analytic review of cross-cultural moderation, behavioral mediation, and honesty-humility.}, journal = {The Journal of applied psychology}, volume = {109}, number = {9}, pages = {1489-1511}, doi = {10.1037/apl0001182}, pmid = {38635204}, issn = {1939-1854}, mesh = {Humans ; *Leadership ; *Personality ; *Cross-Cultural Comparison ; Social Behavior ; }, abstract = {We advance the trait approach to leadership by leveraging a large multinational database on leader emergence (k = 120 samples, N = 32,579) and leader effectiveness (k = 116, N = 42,487) to extend Judge et al.'s (2002) classic meta-analysis of Big Five personality and leadership. By testing novel hypotheses rooted in culturally endorsed implicit leadership theory and socioanalytic theory, we offer three unique insights. First, in collectivist societies (cultures that value interdependence with one's group), the five factor model traits-and leader Extraversion and Agreeableness in particular-are stronger predictors of leader effectiveness, consistent with the theorized need for enhanced social coordination in such cultures. Second, a theoretical model is proposed to specify that leader Big Five trait effects are mediated by leader behavior (confirming that Consideration mediates Extraversion and Agreeableness, whereas Initiating Structure mediates Conscientiousness, Extraversion, and Openness). Third, trait Honesty-Humility robustly predicts leader effectiveness beyond the Big Five traits, expanding the trait approach. New implications for understanding when and why personality traits predict leadership are discussed. (PsycInfo Database Record (c) 2024 APA, all rights reserved).}, } @article {pmid38634768, year = {2024}, author = {Murray, AJ and Durrheim, K}, title = {Studying intersectionality using ideological dilemmas: The case of paid domestic labour.}, journal = {The British journal of social psychology}, volume = {63}, number = {4}, pages = {1743-1756}, doi = {10.1111/bjso.12750}, pmid = {38634768}, issn = {2044-8309}, mesh = {Humans ; Female ; Adult ; *Employment ; Women, Working/psychology ; Household Work ; }, abstract = {Intersectionality has gained a great deal of academic purchase within the social sciences but there is still a need for further conceptual and methodological innovation and clarity. As such, this study uses paid domestic labour as a case study to apply Billig et al.'s (Ideological dilemmas: A social psychology of everyday thinking, 1988) notion of ideological dilemmas to explore the common sense that paid domestic workers draw on to position themselves as women and workers. The analysis highlights how participants use (often contradictory) themes of common sense when speaking about their place in the household through dilemmas of servitude, belonging, and intimacy. Speakers draw on gendered ideology, not as a fixed set of ideas, but rather as a mobile discursive resource that can be deployed in situ, allowing them to justify, subvert, and evaluate social positions of domestic womanhood. The study provides both a conceptual window and a robust method for studying nonessentialist intersectionality through ideological dilemmas.}, } @article {pmid38631676, year = {2024}, author = {Wolbers, M and Noci, A and Delmar, P and Yiu, S and Bartlett, JW}, title = {Rejoinder to the letter: "Standard and reference-based conditional mean imputation: Regulators and trial statisticians be aware!".}, journal = {Pharmaceutical statistics}, volume = {23}, number = {5}, pages = {604-610}, doi = {10.1002/pst.2374}, pmid = {38631676}, issn = {1539-1612}, mesh = {Humans ; Data Interpretation, Statistical ; *Bayes Theorem ; Research Design ; Models, Statistical ; Clinical Trials as Topic/methods/statistics & numerical data ; }, abstract = {We appreciate Cro et al.'s efforts to bring wider attention to the debate surrounding variance estimation for reference-based imputation methods. However, we believe that the way this debate is presented as "multiple imputation" versus "conditional mean imputation" can be misleading. Both of these imputation methods rely on identical assumptions and provide essentially identical treatment effect estimates. While conditional mean imputation naturally focuses on the frequentist repeated sampling variance, we show here that it can be easily adapted to target a variance with similar properties to Rubin's variance. Therefore, conditional mean imputation combined with jackknife resampling remains a valid and effective deterministic method for handling missing data under missing-at-random or reference-based assumptions regardless of the user's preference for variance estimation. We also reappraise the frequentist variance by arguing that it correctly reflects the strong assumptions of reference-based imputation. In contrast, we are not aware of any frequentist or Bayesian framework under which Rubin's variance provides correct inference.}, } @article {pmid38629547, year = {2024}, author = {Huang, SW and Zhao, YK and Zhu, XY and Liu, HL and Liu, JJ and Chen, S and Chen, JY and Zhang, AF}, title = {[Integrated Analysis of Soil Organic Matter Molecular Composition Changes Under Different Land Uses].}, journal = {Huan jing ke xue= Huanjing kexue}, volume = {45}, number = {5}, pages = {2848-2858}, doi = {10.13227/j.hjkx.202306067}, pmid = {38629547}, issn = {0250-3301}, abstract = {The application of biomarkers to study the molecular composition of soil organic matter (SOM) can be used to analyze the source and degradation of SOM and reveal the stability mechanism of soil organic carbon (SOC) at the molecular level. In order to further clarify the effects of different land use patterns (farmland, grassland, and forest) on the molecular composition of SOM, the changes in molecular composition of organic matter (free lipids, cutin, suberin, and lignin) on a global scale were studied using a meta-analysis method. The results showed that there were significant differences in the molecular composition of organic matter under different land use patterns. The contents of free lipids (n-alkanes, n-alkanols, n-alkanoic acids, and cyclic lipids), cutin, and lignin phenols in forest soil were significantly higher than those in grassland and farmland. There was no significant difference in the content of suberin between grassland and forest soil. The ratio of suberin to cutin in grassland was the highest, with an average of 2.96, and the averages of farmland and forest were 1.68 and 2.21, respectively. The ratio of syringic acid to syringaldehyde (Ad/Al)S and the ratio of vanillic acid to vanillin (Ad/Al)V of farmland soil were the largest, which were 1.25 and 1.58, respectively, and were significantly higher than those in grassland (0.46 and 0.69) and forest (0.78 and 0.7). The results of correlation analysis showed that in farmland soil, suberin was significantly correlated with mean annual precipitation (MAP) and clay; cutin was significantly correlated with clay; and lignin was significantly correlated with mean annual temperature (MAT), MAP, sand, and bulk density. In grassland soil, total free lipids were significantly correlated with MAP and bulk density; suberin and cutin were significantly correlated with MAT and MAP; and lignin was significantly correlated with MAP, pH, sand, and bulk density. However, only lignin was significantly correlated with MAP and sand in forest soils. Overall, the contents of SOC and molecular components in forest soil were higher under the three land use practices, and the contribution of plant roots to SOM in grassland soil was greater. In farmland soil, the degradation of lignin was accelerated due to human farming activities. Future research should focus on the regulation of soil physicochemical properties and climatic conditions on the molecular composition of SOM.}, } @article {pmid38619501, year = {2024}, author = {Xu, Z and Zhang, Y}, title = {Reevaluating the Case of an Allegedly Absent Circumflex Artery: A Detailed Analysis of İnce et al.'s Report.}, journal = {Anatolian journal of cardiology}, volume = {28}, number = {5}, pages = {258-259}, pmid = {38619501}, issn = {2149-2271}, } @article {pmid38619500, year = {2024}, author = {İnce, O and Gülşen, K and Tuğrul, S and Şahin, İ and Okuyan, E}, title = {Reply to Letter to the Editor: 'Reevaluating the Case of an Allegedly Absent Circumflex Artery: A Detailed Analysis of İnce et al.'s Report'.}, journal = {Anatolian journal of cardiology}, volume = {28}, number = {5}, pages = {260-262}, pmid = {38619500}, issn = {2149-2271}, } @article {pmid38610039, year = {2024}, author = {Mäkelä, P and Boaz, A and Oliver, K}, title = {A modified action framework to develop and evaluate academic-policy engagement interventions.}, journal = {Implementation science : IS}, volume = {19}, number = {1}, pages = {31}, pmid = {38610039}, issn = {1748-5908}, mesh = {Humans ; *Ecosystem ; *Organizations ; Health Policy ; Government ; Schools ; }, abstract = {BACKGROUND: There has been a proliferation of frameworks with a common goal of bridging the gap between evidence, policy, and practice, but few aim to specifically guide evaluations of academic-policy engagement. We present the modification of an action framework for the purpose of selecting, developing and evaluating interventions for academic-policy engagement.

METHODS: We build on the conceptual work of an existing framework known as SPIRIT (Supporting Policy In Health with Research: an Intervention Trial), developed for the evaluation of strategies intended to increase the use of research in health policy. Our aim was to modify SPIRIT, (i) to be applicable beyond health policy contexts, for example encompassing social, environmental, and economic policy impacts and (ii) to address broader dynamics of academic-policy engagement. We used an iterative approach through literature reviews and consultation with multiple stakeholders from Higher Education Institutions (HEIs) and policy professionals working at different levels of government and across geographical contexts in England, alongside our evaluation activities in the Capabilities in Academic Policy Engagement (CAPE) programme.

RESULTS: Our modifications expand upon Redman et al.'s original framework, for example adding a domain of 'Impacts and Sustainability' to capture continued activities required in the achievement of desirable outcomes. The modified framework fulfils the criteria for a useful action framework, having a clear purpose, being informed by existing understandings, being capable of guiding targeted interventions, and providing a structure to build further knowledge.

CONCLUSION: The modified SPIRIT framework is designed to be meaningful and accessible for people working across varied contexts in the evidence-policy ecosystem. It has potential applications in how academic-policy engagement interventions might be developed, evaluated, facilitated and improved, to ultimately support the use of evidence in decision-making.}, } @article {pmid38606542, year = {2024}, author = {Diamond, A}, title = {From mutation to management: Advancing Langerhans cell histiocytosis treatment through combination therapies.}, journal = {British journal of haematology}, volume = {204}, number = {5}, pages = {1588-1589}, doi = {10.1111/bjh.19473}, pmid = {38606542}, issn = {1365-2141}, mesh = {Humans ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Disease Management ; *Histiocytosis, Langerhans-Cell/drug therapy/genetics/therapy ; MAP Kinase Signaling System/drug effects ; Mutation ; Protein Kinase Inhibitors/therapeutic use ; }, abstract = {The treatment landscape for relapsed Langerhans cell histiocytosis (LCH) is fraught with uncertainty due to a scarcity of data. Karri et al.'s study provides promising evidence that combining MAPK pathway inhibitors with chemotherapy could improve outcomes, even for patients with multiple relapses. Although larger studies are needed, this approach suggests a shift towards more aggressive, potentially curative strategies in the management of LCH. Commentary on: Karri et al. Clinical, radiological and molecular responses to combination chemotherapy with MAPK pathway inhibition in relapsed and refractory Langerhans cell histiocytosis. Br J Haematol 2024;204:1882-1887.}, } @article {pmid38604121, year = {2024}, author = {C, BG and Zhou, P and Wu, C}, title = {Fusobacterium nucleatum subsp. animalis comes to the spotlight in oral diseases.}, journal = {Cell host & microbe}, volume = {32}, number = {4}, pages = {443-444}, doi = {10.1016/j.chom.2024.03.009}, pmid = {38604121}, issn = {1934-6069}, support = {R01 DE030895/DE/NIDCR NIH HHS/United States ; }, mesh = {*Fusobacterium ; *Fusobacterium nucleatum ; }, abstract = {Krieger et al.'s study in this issue of Cell Host & Microbe reveals that Fusobacterium nucleatum subsp. animalis strains, previously underestimated, are significant in disease-affected oral areas. This challenges the long-held notion of the dominance of Fusobacterium nucleatum subsp. nucleatum, reshaping our understanding of Fusobacterium distribution in the oral microbiome.}, } @article {pmid38602953, year = {2023}, author = {Biesaga, M and Domaradzka, A and Roszczyńska-Kurasińska, M and Talaga, S and Nowak, A}, title = {The effect of the pandemic on European narratives on smart cities and surveillance.}, journal = {Urban studies (Edinburgh, Scotland)}, volume = {60}, number = {10}, pages = {1894-1914}, pmid = {38602953}, issn = {0042-0980}, abstract = {This article presents an analysis of European smart city narratives and how they evolved under the pressure of the COVID-19 pandemic. We start with Joss et al.'s observation that the smart-city discourse is presently in flux, engaged in intensive boundary-work and struggling to gain wider support. We approach this process from the critical perspective of surveillance capitalism, as proposed by Zuboff, to highlight the growing privacy concerns related to technological development. Our results are based on analysing 184 articles regarding smart-city solutions, published on social media by five European journals between 2017 and 2021. We adopted both human and machine coding processes for qualitative and quantitative analysis of our data. As a result, we identified the main actors and four dominant narratives: regulation of artificial intelligence and facial recognition, technological fight with the climate emergency, contact tracing apps and the potential of 5G technology to boost the digitalisation processes. Our analysis shows the growing number of positive narratives underlining the importance of technology in fighting the pandemic and mitigating the climate emergency, but the latter is often mentioned in a tokenistic fashion. Right to privacy considerations are central for two out of four discovered topics. We found that the main rationale for the development of surveillance technologies relates to the competitiveness of the EU in the global technological rivalry, while ambitions like increasing societal well-being or safeguarding the transparency of new policies are nearly non-existent.}, } @article {pmid38599206, year = {2024}, author = {Nohria, A and Desai, D and Lo Sicco, K and Shapiro, J}, title = {Comment on Luo et al.'s "A Bibliometrics of the Treatment of Alopecia Areata in the Past Twenty Years".}, journal = {Dermatology (Basel, Switzerland)}, volume = {240}, number = {4}, pages = {684-686}, pmid = {38599206}, issn = {1421-9832}, mesh = {*Alopecia Areata/drug therapy ; Humans ; *Bibliometrics ; }, } @article {pmid38596406, year = {2024}, author = {Tanaka, Y and Kozuma, L and Hino, H and Takeya, K and Eto, M}, title = {Abemaciclib and Vacuolin-1 decrease aggregate-prone TDP-43 accumulation by accelerating autophagic flux.}, journal = {Biochemistry and biophysics reports}, volume = {38}, number = {}, pages = {101705}, pmid = {38596406}, issn = {2405-5808}, abstract = {(Macro)autophagy is a cellular degradation system for unnecessary materials, such as aggregate-prone TDP-43, a central molecule in neurodegenerative diseases including amyotrophic lateral sclerosis and frontotemporal lobar degeneration. Abemaciclib (Abe) and vacuolin-1 (Vac) treatments are known to induce vacuoles characterized by an autophagosome and a lysosome component, suggesting that they facilitate autophagosome-lysosome fusion. However, it remains unknown whether Abe and Vac suppress the accumulation of aggregate-prone TDP-43 by accelerating autophagic flux. In the present study, the Abe and Vac treatment dose-dependently reduced the GFP/RFP ratio in SH-SY5Y neuroblastoma cells stably expressing the autophagic flux marker GFP-LC3-RFP-LC3ΔG. Abe and Vac also increased the omegasome marker GFP-ATG13 signal and the autophagosome marker mCherry-LC3 localized to the lysosome marker LAMP1-GFP. The Abe and Vac treatment decreased the intracellular level of the lysosome marker LAMP1-GFP in SH-SY5Y cells stably expressing LAMP1-GFP, but did not increase the levels of LAMP1-GFP, the autophagosome marker LC3-II, or the multivesicular body marker TSG101 in the extracellular vesicle-enriched fraction. Moreover, Abe and Vac treatment autophagy-dependently inhibited GFP-tagged aggregate-prone TDP-43 accumulation. The results of a PI(3)P reporter assay using the fluorescent protein tagged-2 × FYVE and LAMP1-GFP indicated that Abe and Vac increased the intensity of the PI(3)P signal on lysosomes. A treatment with the VPS34 inhibitor wortmannin (WM) suppressed Abe-/Vac-facilitated autophagic flux and the degradation of GFP-tagged aggregate-prone TDP-43. Collectively, these results suggest that Abe and Vac degrade aggregate-prone TDP-43 by accelerating autophagosome formation and autophagosome-lysosome fusion through the formation of PI(3)P.}, } @article {pmid38594217, year = {2024}, author = {Lenton, E and Kagan, D and Seear, K and Mulcahy, S and Farrugia, A and Valentine, K and Edwards, M and Jeffcote, D}, title = {Troubling complaint: Addressing hepatitis C-related stigma and discrimination through complaint mechanisms.}, journal = {Sociology of health & illness}, volume = {46}, number = {7}, pages = {1400-1418}, doi = {10.1111/1467-9566.13776}, pmid = {38594217}, issn = {1467-9566}, support = {DP200100941//Australian Research Council/ ; }, mesh = {Humans ; *Social Stigma ; *Hepatitis C/psychology ; Australia ; Female ; Male ; Interviews as Topic ; Adult ; Middle Aged ; Social Discrimination/psychology ; Qualitative Research ; }, abstract = {The need to grapple with hepatitis C-related stigma and discrimination in Australian health-care settings has been recognised in public policy, and work is underway to address it. But how likely are people to raise a complaint when they experience stigma or discrimination? And how effective and accessible are complaints mechanisms? Given complaint procedures are considered important parts of the delivery of safe and ethical health care, these are important questions that have yet to be substantially explored. Drawing on interviews with people with lived experience of hepatitis C (n = 30), this article considers how affected people feel about complaints processes and the act of complaining. Alongside these perspectives, we discuss complaint mechanisms, and the views of stakeholders who work with hepatitis C-affected communities in policy, health, legal and advocacy roles (n = 30) on the institutional and cultural dynamics of complaint. We draw on Sara Ahmed's Complaint! and Fraser et al.'s work on drug-related stigma to analyse these concerns that have yet to be researched, and argue that the (unlikely) prospect of successful complaint is a key part of the network of forces that perpetuate stigma, discrimination and disadvantage among people who have (lived with) hepatitis C. Although people with lived experience are often powerful advocates and acutely aware of the deficiencies in the quality of their treatment, our interviews suggest that the obstacles they face to accessing health care are seen as commonplace, intractable and insurmountable; and, that mechanisms for addressing them-where they exist at all-treat complaints in narrowly individualising terms and expose complainants to dismissal. Following Ahmed, we call for a 'troubling' of complaints-responding to them not as individual problems but rather as collective, structural concerns, necessitating new approaches.}, } @article {pmid38568405, year = {2024}, author = {Schlier, B and Ellett, L and Thompson, E and Gaudiano, B and Krkovic, K and Kingston, JL}, title = {Measuring Paranoid Beliefs in Adolescents: A Comparison of the Revised-Green et al.'s Paranoid Thoughts Scale (R-GPTS) and the Bird Checklist of Adolescent Paranoia (B-CAP).}, journal = {Research on child and adolescent psychopathology}, volume = {52}, number = {8}, pages = {1319-1327}, pmid = {38568405}, issn = {2730-7174}, mesh = {Humans ; Adolescent ; Female ; Male ; *Paranoid Disorders/psychology/diagnosis ; Cross-Sectional Studies ; *Psychometrics/instrumentation/methods ; Reproducibility of Results ; Psychiatric Status Rating Scales/standards ; Checklist ; United States/epidemiology ; United Kingdom ; }, abstract = {Research on paranoid beliefs in adolescents is in its infancy. Valid and reliable assessments are essential to advancing the field, yet there is no current consensus as to which are optimal to use in this population. This study compared the psychometric properties of two measures of paranoia in a general population adolescent sample. A cross-sectional study with quota sampling (gender and age) recruited adolescents (14-17 years) from the UK (n = 262) and USA (n = 200), who completed the Revised Green et al. Paranoid Thoughts Scale (R-GPTS) and the Bird Checklist for Adolescent Paranoia (B-CAP). We assessed factor structures, intercorrelations, overlap of participants identified as at-risk for paranoid thoughts via both scales, convergent validity (scales with one another) and discriminant validity (distress, wellbeing, bullying and discrimination). Both scales performed equally well in terms of factorial validity. Intercorrelations between the subscales and with general distress were high for both measures. However, a substantial percentage of participants were identified as having paranoid beliefs according to the R-GPTS but not the B-CAP. Furthermore, the B-CAP showed a very high correlations (0.69 ≤ r ≤ 0.79) with self-reported bullying experiences, which bordered on multicollinearity. Findings highlight the possibility that B-CAP may risk confounding paranoid beliefs with exposure to bullying more so than R-GPTS, and that B-CAP may miss instances of elevated paranoia that are captured by the R-GPTS. Future research needs to further explore this by validating both scales with an external (e.g., interview-based) criterion for paranoia.}, } @article {pmid38556034, year = {2024}, author = {Zhang, MD and Huang, WY and Luo, JY and He, RQ and Huang, ZG and Li, JD and Qin, F and Chen, G and Lei, L}, title = {The 'whole landscape' of research on systemic sclerosis over the past 73 years.}, journal = {Autoimmunity reviews}, volume = {23}, number = {5}, pages = {103538}, doi = {10.1016/j.autrev.2024.103538}, pmid = {38556034}, issn = {1873-0183}, mesh = {Humans ; *Bibliometrics ; Biomedical Research/trends/history ; History, 21st Century ; *Scleroderma, Systemic/history/immunology/physiopathology ; History, 20th Century ; }, abstract = {OBJECTIVE: This study aimed to analyse existing research on systemic sclerosis (SSc) conducted over the past 73 years to develop an essential reference for a comprehensive and objective understanding of this field of inquiry.

METHODS: Using the Web of Science Core Collection, PubMed, and Scopus databases as data sources for the bibliometric analysis, we searched for published literature related to SSc over the past 73 years. The Bibliometrix package was used to analyse key bibliometric indicators, such as annual publication volume, countries, journals, author contributions, and research hotspots.

RESULTS: From 1970 to 2022, the number of SSc articles steadily increased, reaching its peak in 2020-2022, with approximately 1200 papers published in each of these three years. Matucci-Cerinic et al.'s team published the most articles (425). The United States (11,282), Italy (7027), and France (5226) were the most predominant contexts. The most influential scholars in the field were Denton, Leroy, Steen, and Khanna, with H-indices of 86, 84, and 83, respectively. Arthritis and Rheumatism was the most influential journal in this field (H-index 142). High-frequency keywords in the SSc field included fibrosis (738), inflammation (242), vasculopathy (145), fibroblasts (120), and autoantibodies (118) with respect to pathogenesis, and interstitial lung disease (ILD, 708), pulmonary arterial hypertension (PAH, 696), and Raynaud's phenomenon (326) with regards to clinical manifestations.

CONCLUSION: In the past three years, SSc research has entered a period of rapid development, mainly driven by research institutions in Europe and the United States. The most influential journal has been Arthritis and Rheumatism, and autoimmune aspects, vasculopathy, fibrogenesis, PAH, and ILD remain the focus of current research and indicate trends in future research.}, } @article {pmid38530617, year = {2024}, author = {Jiang, C and Chen, Z and Wolfe, JM}, title = {Toward viewing behavior for aerial scene categorization.}, journal = {Cognitive research: principles and implications}, volume = {9}, number = {1}, pages = {17}, pmid = {38530617}, issn = {2365-7464}, support = {R01 CA207490/CA/NCI NIH HHS/United States ; R01 EY017001/EY/NEI NIH HHS/United States ; EY017001/EY/NEI NIH HHS/United States ; CA207490/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; Photic Stimulation/methods ; *Visual Perception ; *Eye Movements ; Automation ; Records ; }, abstract = {Previous work has demonstrated similarities and differences between aerial and terrestrial image viewing. Aerial scene categorization, a pivotal visual processing task for gathering geoinformation, heavily depends on rotation-invariant information. Aerial image-centered research has revealed effects of low-level features on performance of various aerial image interpretation tasks. However, there are fewer studies of viewing behavior for aerial scene categorization and of higher-level factors that might influence that categorization. In this paper, experienced subjects' eye movements were recorded while they were asked to categorize aerial scenes. A typical viewing center bias was observed. Eye movement patterns varied among categories. We explored the relationship of nine image statistics to observers' eye movements. Results showed that if the images were less homogeneous, and/or if they contained fewer or no salient diagnostic objects, viewing behavior became more exploratory. Higher- and object-level image statistics were predictive at both the image and scene category levels. Scanpaths were generally organized and small differences in scanpath randomness could be roughly captured by critical object saliency. Participants tended to fixate on critical objects. Image statistics included in this study showed rotational invariance. The results supported our hypothesis that the availability of diagnostic objects strongly influences eye movements in this task. In addition, this study provides supporting evidence for Loschky et al.'s (Journal of Vision, 15(6), 11, 2015) speculation that aerial scenes are categorized on the basis of image parts and individual objects. The findings were discussed in relation to theories of scene perception and their implications for automation development.}, } @article {pmid38530446, year = {2024}, author = {Duwe, G and Haferkamp, A and Höfner, T}, title = {Author reply on the Letter to the Editor on "Standardized reports of focal-HIFU results is paramount: a closer look at the Duwe et al.'s cohort on focal HIFU for localized prostate cancer".}, journal = {World journal of urology}, volume = {42}, number = {1}, pages = {190}, pmid = {38530446}, issn = {1433-8726}, mesh = {Male ; Humans ; *Prostatic Neoplasms/surgery ; *Ultrasound, High-Intensity Focused, Transrectal ; Treatment Outcome ; }, } @article {pmid38523029, year = {2024}, author = {Dal-Ré, R}, title = {Peer-review: Considerations to Candal-Pedreira et al.'s proposals.}, journal = {Anales de pediatria}, volume = {100}, number = {4}, pages = {311-312}, doi = {10.1016/j.anpede.2024.01.017}, pmid = {38523029}, issn = {2341-2879}, mesh = {Humans ; *Peer Review, Research ; Peer Review ; Pediatrics ; Periodicals as Topic ; }, } @article {pmid38522247, year = {2024}, author = {Flodgren, GM and Bezuidenhoudt, JE and Alkanhal, N and Brinkwirth, S and Lee, ACK}, title = {Conceptualisation and implementation of integrated disease surveillance globally: a scoping review.}, journal = {Public health}, volume = {230}, number = {}, pages = {105-112}, doi = {10.1016/j.puhe.2024.02.018}, pmid = {38522247}, issn = {1476-5616}, mesh = {Humans ; *Pandemics ; Concept Formation ; *COVID-19/epidemiology ; Africa/epidemiology ; }, abstract = {OBJECTIVES: The objective of this study was to examine the conceptualisation and operationalisation of Integrated Disease Surveillance (IDS) systems globally and the evidence for their effectiveness. Furthermore, to determine whether the recommendations made by Morgan et al. are supported by the evidence and what the evidence is to inform country development of IDS.

STUDY DESIGN: The study incorporated a scoping review.

METHODS: This review summarised evidence meeting the following inclusion criteria: Participants: any health sector; Concept: IDS; and Context: global. We searched Medline, Embase, and Epistemonikos for English publications between 1998 and 2022. Standard review methods were applied. A bespoke conceptual framework guided the narrative analysis. This scoping review is part of a research programme with three key elements, with the other studies being a survey of the International Association of National Public Health Institutes members on the current status of their disease surveillance systems and a deeper analysis and case studies of the surveillance systems in seven countries, to highlight the opportunities and challenges of integration.

RESULTS: Eight reviews and five primary studies, which were assessed as being of low quality, were included, mostly examining IDS in Africa, the human sector, and communicable diseases. None reported on the effects on disease control or on the evolution of IDS during the COVID-19 pandemic. Descriptions of IDS and of integration varied. Prerequisites of effective IDS systems mostly related to the adequacy of core functions and resourcing requirements. Laws or regulations supporting system integration and data sharing were not addressed. The provision of core functions and resourcing requirements were described as inadequate, financing as non-sustainable, and governance as poor. Enablers included active data sharing, close cooperation between agencies, clear reporting channels, integration of vertical programs, increased staff training, and adopting mobile reporting. Whilst the conceptual framework for IDS and Morgan et al.'s proposed principles were to some extent reflected in the highlighted priorities for IDS in the literature, the evidence base remains weak.

CONCLUSIONS: Available evidence is fragmented, incomplete, and of poor quality. The review found a lack of robust evaluation studies on the impact of IDS on disease control. Whilst a lack of evidence does not imply a lack of benefit or effect, it should signal the need to evaluate the process and impact of integration in the future development of surveillance systems. A common IDS definition and articulation of the parts that constitute an IDS system are needed. Further robust impact evaluations, as well as country reviews and evaluations of their IDS systems, are required to improve the evidence base.}, } @article {pmid38520811, year = {2024}, author = {Li, J and Hodson, ME and Brown, CD and Bottoms, MJ and Ashauer, R and Alvarez, T}, title = {Evaluation of models to estimate the bioaccumulation of organic chemicals in earthworms.}, journal = {Ecotoxicology and environmental safety}, volume = {275}, number = {}, pages = {116240}, doi = {10.1016/j.ecoenv.2024.116240}, pmid = {38520811}, issn = {1090-2414}, mesh = {Animals ; *Oligochaeta ; *Soil Pollutants/analysis ; Bioaccumulation ; *Pesticides ; Organic Chemicals ; Soil/chemistry ; }, abstract = {Modelling approaches to estimate the bioaccumulation of organic chemicals by earthworms are important for improving the realism in risk assessment of chemicals. However, the applicability of existing models is uncertain, partly due to the lack of independent datasets to test them. This study therefore conducted a comprehensive literature review on existing empirical and kinetic models that estimate the bioaccumulation of organic chemicals in earthworms and gathered two independent datasets from published literature to evaluate the predictive performance of these models. The Belfroid et al. (1995a) model is the best-performing empirical model, with 91.2% of earthworm body residue simulations within an order of magnitude of observation. However, this model is limited to the more hydrophobic pesticides and to the earthworm species Eisenia fetida or Eisenia andrei. The kinetic model proposed by Jager et al. (2003b) which out-performs that of Armitage and Gobas (2007), predicted uptake of PCB 153 in the earthworm E. andrei to within a factor of 10. However, the applicability of Jager et al.'s model to other organic compounds and other earthworm species is unknown due to the limited evaluation dataset. The model needs to be parameterised for different chemical, soil, and species types prior to use, which restricts its applicability to risk assessment on a broad scale. Both the empirical and kinetic models leave room for improvement in their ability to reliably predict bioaccumulation in earthworms. Whether they are fit for purpose in environmental risk assessment needs careful consideration on a case by case basis.}, } @article {pmid38514494, year = {2024}, author = {Lehmann, RJB and Schäfer, T and Bartels, R and Sabic, S and Schache, C}, title = {Testing the Factor Structure and Construct Validity of the German Version of Gray et al.'s (2003) Sexual Fantasy Questionnaire.}, journal = {Archives of sexual behavior}, volume = {53}, number = {6}, pages = {2225-2236}, pmid = {38514494}, issn = {1573-2800}, mesh = {Humans ; Female ; Adult ; Male ; Surveys and Questionnaires/standards ; *Sexual Behavior/psychology ; *Fantasy ; Factor Analysis, Statistical ; Reproducibility of Results ; Germany ; Middle Aged ; Psychometrics ; Adolescent ; Young Adult ; Self Report/standards ; }, abstract = {Gray et al.'s (2003) Sexual Fantasy Questionnaire (SFQ) is becoming an increasingly used self-report measure of sexual fantasy use. The current study analyzed the factorial structure and construct validity of the behavioral items of the SFQ using a nomological network of other sexuality-related measures in a large German-speaking sample (N = 846). Participants' (27.7% females) mean age was 30.8 years (SD = 11.0). Exploratory factor analysis revealed a 65-item scale comprising five-factors, which were termed: normophilic sexual fantasies, sexualized aggression, sexualized submission, submissive courtship, and bodily functions. This German version of the SFQ was found to have high construct validity indicated by its association with other related constructs. Based on these results, we argue that the SFQ is a valid self-report measure that can be used in both research and clinical practice (foremost the factors sexualized aggression and sexualized submission). Suggestions for future research are discussed in light of the results and the study's limitations.}, } @article {pmid38512564, year = {2024}, author = {Rimmer, B and Balla, M and Dutton, L and Williams, S and Araújo-Soares, V and Gallagher, P and Finch, T and Lewis, J and Burns, R and Menger, F and Sharp, L and , }, title = {Barriers and facilitators to self-management in people living with a lower-grade glioma.}, journal = {Journal of cancer survivorship : research and practice}, volume = {}, number = {}, pages = {}, pmid = {38512564}, issn = {1932-2267}, support = {GN-000435//Brain Tumour Charity/ ; GN-000435//Brain Tumour Charity/ ; GN-000435//Brain Tumour Charity/ ; GN-000435//Brain Tumour Charity/ ; GN-000435//Brain Tumour Charity/ ; GN-000435//Brain Tumour Charity/ ; GN-000435//Brain Tumour Charity/ ; GN-000435//Brain Tumour Charity/ ; GN-000435//Brain Tumour Charity/ ; GN-000435//Brain Tumour Charity/ ; }, abstract = {PURPOSE: Self-management can have clinical and quality-of-life benefits. However, people with lower-grade gliomas (LGG) may face chronic tumour- and/or treatment-related symptoms and impairments (e.g. cognitive deficits, seizures), which could influence their ability to self-manage. Our study aimed to identify and understand the barriers and facilitators to self-management in people with LGG.

METHODS: We conducted semi-structured interviews with 28 people with LGG across the United Kingdom, who had completed primary treatment. Sixteen participants were male, mean age was 50.4 years, and mean time since diagnosis was 8.7 years. Interviews were audio-recorded and transcribed. Following inductive open coding, we deductively mapped codes to Schulman-Green et al.'s framework of factors influencing self-management, developed in chronic illness.

RESULTS: Data suggested extensive support for all five framework categories ('Personal/lifestyle characteristics', 'Health status', 'Resources', 'Environmental characteristics', 'Healthcare system'), encompassing all 18 factors influencing self-management. How people with LGG experience many of these factors appears somewhat distinct from other cancers; participants described multiple, often co-occurring, challenges, primarily with knowledge and acceptance of their incurable condition, the impact of seizures and cognitive deficits, transport difficulties, and access to (in)formal support. Several factors were on a continuum, for example, sufficient knowledge was a facilitator, whereas lack thereof, was a barrier to self-management.

CONCLUSIONS: People with LGG described distinctive experiences with wide-ranging factors influencing their ability to self-manage.

These findings will improve awareness of the potential challenges faced by people with LGG around self-management and inform development of self-management interventions for this population.}, } @article {pmid38511853, year = {2024}, author = {Campagna, MP and Havrdova, EK and Horakova, D and Izquierdo, G and Matesanz, F and Eichau, S and Lechner-Scott, J and Taylor, BV and García-Sanchéz, MI and Alcina, A and van der Walt, A and Butzkueven, H and Jokubaitis, VG}, title = {No evidence for association between rs10191329 severity locus and longitudinal disease severity in 1813 relapse-onset multiple sclerosis patients from the MSBase registry.}, journal = {Multiple sclerosis (Houndmills, Basingstoke, England)}, volume = {30}, number = {9}, pages = {1216-1220}, pmid = {38511853}, issn = {1477-0970}, mesh = {Humans ; *Registries ; *Severity of Illness Index ; Longitudinal Studies ; Adult ; Male ; Female ; *Multiple Sclerosis, Relapsing-Remitting/genetics ; Polymorphism, Single Nucleotide ; Middle Aged ; Multiple Sclerosis/genetics ; Genotype ; }, abstract = {BACKGROUND: The International Multiple Sclerosis Genetics Consortium and MultipleMS Consortium recently reported a genetic variant associated with multiple sclerosis (MS) severity. However, it remains unclear if these variants remain associated with more robust, longitudinal measures of disease severity.

METHODS: We examined the top variant, rs10191329, from Harroud et al.'s study in 1813 relapse-onset MS patients from the MSBase Registry to assess association with longitudinal disease severity.

RESULTS: Our analysis revealed no significant association between rs10191329 genotype and longitudinal binary disease severity (p > 0.05).

CONCLUSION: These findings highlight the complexity of genetic factors mediating long-term MS outcomes and the need for further research.}, } @article {pmid38509039, year = {2024}, author = {Klein, LB and Melnik, J and Curran, K and Luebke, J and Moore, KM and Ruiz, AM and Brown, C and Parker, D and Hernandez-White, I and Walsh, K}, title = {Trauma- and Violence-Informed Empowering Care for Sexual Assault Survivors.}, journal = {Journal of forensic nursing}, volume = {20}, number = {3}, pages = {166-173}, pmid = {38509039}, issn = {1939-3938}, support = {UL1 TR002373/TR/NCATS NIH HHS/United States ; }, mesh = {Humans ; *Forensic Nursing ; *Sex Offenses ; *Survivors/psychology ; Crime Victims/psychology ; Nurse-Patient Relations ; Empowerment ; Empathy ; Trust ; }, abstract = {BACKGROUND: Forensic nurse examiners, including sexual assault nurse examiners, provide care for survivors holistically through healthcare, emotional support, connection to follow-up care, safety planning, and, if desired, evidence collection to aid in the prosecution of sexual assault. There is increasing recognition that trauma-informed care must also include an understanding of the impacts of structural violence on minoritized patients to ensure health equity.

AIM: To help address this guidance gap, we expanded Campbell and colleagues' empowering care model using a trauma- and violence-informed care (TVIC) lens.

METHODS: We used an iterative discussion-based process that included five joint meetings between a seven-member transdisciplinary research team and a five-member nurse advisory board.

RESULTS: In a TVIC-informed empowering care model, we propose behavioral examples for forensic nurses for each of Campbell et al.'s five key domains of empowering care for forensic nurse examinations (i.e., build rapport and establish trust, show compassion, provide patient-directed care, convey professionalism, and provide resource referral and follow-up).

CONCLUSIONS: These behavioral examples for nurses can help guide forensic nurse training and practice to reduce disparities in treatment and follow-up support. Structures and systems are needed that enable forensic nurses to provide trauma- and violence-informed empowering care to survivors of sexual assault and, over time, increase the accessibility of forensic nurse examinations and improve patient outcomes.}, } @article {pmid38508134, year = {2024}, author = {Marchand, S}, title = {Unlocking hypnotizability: Transcranial brain stimulation for enhanced impact in chronic pain.}, journal = {Cell reports. Medicine}, volume = {5}, number = {3}, pages = {101475}, pmid = {38508134}, issn = {2666-3791}, mesh = {Humans ; *Chronic Pain/therapy ; *Hypnosis ; Brain ; }, abstract = {Hypnosis provides a therapeutic option for health issues like chronic pain, but individual responsiveness, termed hypnotizability, varies. Faerman et al.'s[1] study showed that transcranial magnetic stimulation (TMS) can significantly improve hypnotizability, offering potential for patients with limited response to hypnosis in pain management.}, } @article {pmid38502837, year = {2024}, author = {Kowalczyk, DM}, title = {Commentary on: "Outcomes of Autologous Versus Irradiated Homologous Costal Cartilage Grafts in Rhinoplasty" by Virginia E. Drake et al.}, journal = {Facial plastic surgery & aesthetic medicine}, volume = {26}, number = {5}, pages = {582-583}, doi = {10.1089/fpsam.2024.0024}, pmid = {38502837}, issn = {2689-3622}, mesh = {*Rhinoplasty/methods ; Humans ; *Costal Cartilage/transplantation ; *Transplantation, Autologous/methods ; Transplantation, Homologous/methods ; Treatment Outcome ; }, abstract = {In this commentary, I discuss Drake et al.'s manuscript, "Outcomes of Autologous versus Irradiated Homologous Costal Cartilage Grafts in Rhinoplasty"[1] and its greater implications for cartilage selection for grafting in septorhinoplasty. The authors provide a robust institutional example of the similarities shared between both autologous costal cartilage and irradiated homologous costal cartilage in terms of warping, infection, resorption, and overall result possible. This study adds to the current body of literature regarding this topic and helps surgeons make better, evidence-based decisions regarding cartilage grafting for their rhinoplasty patients.}, } @article {pmid38502230, year = {2024}, author = {Monsma, E and Seiler, BD}, title = {Picture this! Suggested instructions for guiding the Neuroscience of action imagery: A commentary on Krüger et al. (2022).}, journal = {Psychological research}, volume = {88}, number = {6}, pages = {1885-1887}, pmid = {38502230}, issn = {1430-2772}, mesh = {Humans ; *Imagination/physiology ; Neurosciences ; Movement/physiology ; }, abstract = {Our commentary expands the multisensory and modulating factors proposed by Kruger et al.'s (2023) internal models of action imagery and sensory crossovers. We will discuss the essence of imagery experiences as conceptual intersections among sensory, movement and affective properties that require further neuro-anatomical-contextual mapping to better understand the practical application of imagery. Accordingly, we will propose alternative ideas of daisy-chaining and motor imagery systems. The role of imagery speed, and other properties of movement for refining movement and self-regulation will be considered along with sex as a modulating factor in intra-individual abilities to image movement.}, } @article {pmid38499401, year = {2024}, author = {Leite, TRA and de Souza Junior, SA and Silva, ALSD and Gomes, SP and Gomes de Matos E Souza, F and Bisol, LW}, title = {Challenges and missed opportunities in lithium monitoring for bipolar disorder: A reflection on Bosi et al.'s finding.}, journal = {Bipolar disorders}, volume = {26}, number = {4}, pages = {388-389}, doi = {10.1111/bdi.13417}, pmid = {38499401}, issn = {1399-5618}, mesh = {Humans ; *Bipolar Disorder/drug therapy ; *Antimanic Agents/therapeutic use ; Lithium Compounds/therapeutic use ; Drug Monitoring/methods ; }, } @article {pmid38494149, year = {2024}, author = {Upadhyay, UD and Adkins, CE}, title = {Deception by obfuscation: Studnicki et al.'s retracted longitudinal cohort study of emergency room utilization following abortion.}, journal = {Contraception}, volume = {134}, number = {}, pages = {110417}, doi = {10.1016/j.contraception.2024.110417}, pmid = {38494149}, issn = {1879-0518}, mesh = {Humans ; Female ; *Mifepristone/administration & dosage ; *Abortion, Induced/legislation & jurisprudence ; Pregnancy ; United States ; Longitudinal Studies ; *Emergency Service, Hospital/statistics & numerical data ; Medicaid ; United States Food and Drug Administration ; Retraction of Publication as Topic ; Abortifacient Agents ; }, abstract = {OBJECTIVES: In November 2022, the anti-abortion advocacy group Alliance for Hippocratic Medicine filed a lawsuit against the U.S. Food and Drug Administration challenging the initial 2000 approval of mifepristone and its subsequent approvals, which removed unnecessary restrictions on its use, by disputing the medication's safety record. Such challenges relied on a study examining the incidence of emergency room visits following medication abortion with mifepristone and procedural abortion using Medicaid claims data from 1999-2015. In February 2024 that study was retracted by its publisher. In this paper, we analyzed the methods and presentations of the data used in the study.

STUDY DESIGN: We drew upon commonly accepted principles in responsible epidemiologic and scientific research to evaluate the methods and presentations of the data and organized our findings into themes.

RESULTS: We found multiple instances of methodological flaws, mischaracterizations, and obfuscations of data in this study, including use of a misleading research question and framing, analytic flaws, inappropriate use of an unvalidated proxy measure for outcomes of interest, and inappropriate and deceptive visualizations of data. In each instance, the resulting effect obfuscated and misrepresented the safety of medication abortion with mifepristone.

CONCLUSIONS: The misrepresentation and exaggeration of data promoted and exacerbated misinterpretations about the study's findings, resulting in substantial harm before it was retracted. Recognizing that ongoing judicial proceedings threaten access to conventional reproductive health care in the United States, public health policies must be informed by scientific and medical literature that is comprehensive, methodologically sound, and absent any obfuscations or misrepresentations.

IMPLICATIONS: Studnicki et al.'s study of emergency room visits after abortion misrepresented the safety of mifepristone with multiple instances of methodological flaws and obfuscations of data. While the study has now been retracted, it led to irrevocable harm, threatening access to medication abortion, which has an established safety record.}, } @article {pmid38492323, year = {2024}, author = {Chinni, SS and Shahnaz, W and Akkanapally, S and Sultana, R and Mula, AP and Balla, SB and Zolotenkova, G and Angelakopoulos, N}, title = {Evaluating legal age of 18 years through observation of third molars using Gambier et al. method in an orthopantomographic sample of subadults from South India.}, journal = {Legal medicine (Tokyo, Japan)}, volume = {68}, number = {}, pages = {102435}, doi = {10.1016/j.legalmed.2024.102435}, pmid = {38492323}, issn = {1873-4162}, mesh = {Humans ; *Molar, Third/diagnostic imaging ; *Age Determination by Teeth/methods ; Adolescent ; Male ; Female ; *Radiography, Panoramic ; Young Adult ; India ; Retrospective Studies ; Forensic Dentistry/methods ; Adult ; Tooth Eruption ; }, abstract = {In forensic practice, medicolegal physicians are often tasked with estimating age using dental evidence. This calls for an uncomplicated, reliable, and reproducible method for dental age estimation, enabling physicians to proceed without specific odontological expertise. Among various dental methods, third molar eruption analyses are less complicated and easier to perform. In our study, we explored the effectiveness of Gambier et al.'s scoring system, which examines the eruption of all third molars. We retrospectively analysed 1032 orthopantomograms (528 males and 504 females) of individuals aged between 15 and 24 years. The mean chronological age increased with the progression of stages (1 to 3) and phases (A to D) of the third molar eruption for both sexes. In terms of stages, none showed significant discrimination between minors (<18 years) and adults (>18 years), especially for males. However, Gambier's phase D displayed a relatively high likelihood of being 18 years or older, with an overall 85.9 % of males and 95.7 % of females having all third molars in stage 3 being 18 years or older. While the tested method could be helpful in indicating the completion of the 18th year of life, caution is advised (due to a high percentage of false positives), and it should be used alongside other age assessment methods by experts.}, } @article {pmid38488428, year = {2024}, author = {Dehkordi, LM and Kianian, T and Nasrabadi, AN}, title = {Nursing students' experience of moral distress in clinical settings: A phenomenological study.}, journal = {Nursing open}, volume = {11}, number = {3}, pages = {e2141}, pmid = {38488428}, issn = {2054-1058}, support = {IR.TUMS.VCR.REC.1397.567//Tehran University of Medical Sciences/ ; }, mesh = {Humans ; *Students, Nursing ; *Education, Nursing, Baccalaureate/methods ; Qualitative Research ; Emotions ; Morals ; }, abstract = {AIM: To explore nursing students' moral distress (MD) experiences in clinical settings.

DESIGN: An interpretative phenomenological analysis (IPA) design was employed.

METHODS: Purposive sampling was used. In-depth semi-structured face-to-face interviews were conducted from December 2020 to June 2021 with nursing students who were taking the internship course in clinical settings. Data analysis was conducted following Dickman et al.'s (1989) method.

RESULTS: Ten nursing students participated in this study. Three main themes were identified, including (1) negative learning environments, (2) internal disgust and (3) threats to professional identity.

CONCLUSION: Findings showed that value conflict, lack of knowledge of ethical standards and its application, and unprofessional approaches result in negative environmental learning perceptions from the nursing students. Therefore, due to being unable to change the situation, they start to feel guilt and shame and, as a result, decide to escape the problem instead of managing it. These feelings lead to internal disgust. This issue indicates the importance of improving the knowledge and perception of these situations. Thus, nursing students must be prepared for the real world, where their ideals are constantly challenged. MDs were experienced as threats to dignity, inequality, distrust, and change of mentality towards nursing, characterised as threats to professional identity. It is suggested to inquire about the process of nursing students' resiliency in morally disturbing situations to deduce the suitable approach for clinical education.}, } @article {pmid38488273, year = {2024}, author = {Power, SJ and Stewart, KE and Tanaka, KA and Butt, AL}, title = {In response: Caution in prediction: Evaluating Zhang et al.'s approach to red blood cell transfusion risk.}, journal = {Transfusion}, volume = {64}, number = {3}, pages = {560-561}, doi = {10.1111/trf.17731}, pmid = {38488273}, issn = {1537-2995}, mesh = {Humans ; *Erythrocyte Transfusion/adverse effects ; Phylogeny ; }, } @article {pmid38487369, year = {2024}, author = {Fagnani, E and Bonì, F and Seneci, P and Gornati, D and Muzio, L and Mastrangelo, E and Milani, M}, title = {Stabilization of the retromer complex: Analysis of novel binding sites of bis-1,3-phenyl guanylhydrazone 2a to the VPS29/VPS35 interface.}, journal = {Computational and structural biotechnology journal}, volume = {23}, number = {}, pages = {1088-1093}, pmid = {38487369}, issn = {2001-0370}, abstract = {The stabilization of the retromer protein complex can be effective in the treatment of different neurological disorders. Following the identification of bis-1,3-phenyl guanylhydrazone 2a as an effective new compound for the treatment of amyotrophic lateral sclerosis, in this work we analyze the possible binding sites of this molecule to the VPS35/VPS29 dimer of the retromer complex. Our results show that the affinity for different sites of the protein assembly depends on compound charge and therefore slight changes in the cell microenvironment could promote different binding states. Finally, we describe a novel binding site located in a deep cleft between VPS29 and VPS35 that should be further explored to select novel molecular chaperones for the stabilization of the retromer complex.}, } @article {pmid38487318, year = {2023}, author = {Busch, H}, title = {The Association Between Parental Generativity and Parent-Child Attitude-Similarity Through Parent- and Child-Reported Authoritative Parenting: A Replication.}, journal = {Europe's journal of psychology}, volume = {19}, number = {4}, pages = {348-357}, pmid = {38487318}, issn = {1841-0413}, abstract = {Generativity is the desire to pass something on to the coming generations. Through parents' and children's reports on authoritative parenting, parents' generativity is associated with how similar young adults think their attitudes are to those of their parent (Peterson et al., 1997; https://doi.org/10.1037/0022-3514.72.5.1202). The present study represents a direct replication of these results. Altogether, a sample of 365 German parent-child dyads participated in the study (parents' age: M = 52.87, SD = 4.89; children's age: M = 20.81, SD = 2.26). Parents provided information on their generativity (Loyola Generativity Scale) and parenting styles (Parental Authority Questionnaire). Their child provided information on perceived parenting styles (Parental Authority Questionnaire) and attitudinal similarity to the parent (Psychological Separation Inventory). A serial mediation was found for authoritative parenting. It was not found, however, for authoritarian and permissive parenting. This pattern replicates Peterson et al.'s (1997) results. Potential questions for future research on how generative adults transmit their values and attitudes are discussed.}, } @article {pmid38483050, year = {2024}, author = {Motawea, KR and Nashwan, AJ}, title = {Response to Nguyen et al.'s letter regarding "Anteriolateral versus anterior-posterior electrodes in external cardioversion of atrial fibrillation: A systematic review and meta-analysis of clinical trials".}, journal = {Clinical cardiology}, volume = {47}, number = {3}, pages = {e24253}, pmid = {38483050}, issn = {1932-8737}, mesh = {Humans ; *Atrial Fibrillation/therapy/physiopathology ; *Electric Countershock/instrumentation/methods ; Electrodes ; Meta-Analysis as Topic ; Treatment Outcome ; Systematic Reviews as Topic ; Clinical Trials as Topic ; }, } @article {pmid38481181, year = {2024}, author = {Li, M and Gao, Q and Yang, J and Yu, T}, title = {Evaluating inter-rater reliability in the context of "Sysmex UN2000 detection of protein/creatinine ratio and of renal tubular epithelial cells can be used for screening lupus nephritis": a statistical examination.}, journal = {BMC nephrology}, volume = {25}, number = {1}, pages = {94}, pmid = {38481181}, issn = {1471-2369}, support = {145209121//Fundamental Research Funds in Heilongjiang Provincial Universities/ ; Not available//Heilongjiang Province Leading Talent Echelon Reserve Leader Funding Project/ ; }, mesh = {Humans ; Creatinine ; Reproducibility of Results ; *Lupus Nephritis/diagnosis ; Observer Variation ; Epithelial Cells ; }, abstract = {BACKGROUND: The evaluation of inter-rater reliability (IRR) is integral to research designs involving the assessment of observational ratings by two raters. However, existing literature is often heterogeneous in reporting statistical procedures and the evaluation of IRR, although such information can impact subsequent hypothesis testing analyses.

METHODS: This paper evaluates a recent publication by Chen et al., featured in BMC Nephrology, aiming to introduce an alternative statistical approach to assessing IRR and discuss its statistical properties. The study underscores the crucial need for selecting appropriate Kappa statistics, emphasizing the accurate computation, interpretation, and reporting of commonly used IRR statistics between two raters.

RESULTS: The Cohen's Kappa statistic is typically used for two raters dealing with two categories or for unordered categorical variables having three or more categories. On the other hand, when assessing the concordance between two raters for ordered categorical variables with three or more categories, the commonly employed measure is the weighted Kappa.

CONCLUSION: Chen and colleagues might have underestimated the agreement between AU5800 and UN2000. Although the statistical approach adopted in Chen et al.'s research did not alter their findings, it is important to underscore the importance of researchers being discerning in their choice of statistical techniques to address their specific research inquiries.}, } @article {pmid38479436, year = {2025}, author = {Gimžauskaitė, A and Trumpa, E and Lukoševičius, S and Plisienė, J and Antuševas, A and Velička, L and Benetis, R and Basevičius, A and Inčiūra, D}, title = {Assessment of atherosclerotic plaque morphology using contrast-enhanced ultrasound and its impact on primary cardiovascular events following simultaneous carotid endarterectomy and coronary artery bypass grafting.}, journal = {Vascular}, volume = {33}, number = {1}, pages = {205-211}, doi = {10.1177/17085381241239499}, pmid = {38479436}, issn = {1708-539X}, mesh = {Humans ; *Endarterectomy, Carotid/adverse effects ; *Coronary Artery Bypass/adverse effects ; Male ; Female ; *Plaque, Atherosclerotic ; Aged ; Retrospective Studies ; *Carotid Stenosis/diagnostic imaging/surgery/complications/pathology ; *Contrast Media/administration & dosage ; Predictive Value of Tests ; Middle Aged ; *Coronary Artery Disease/surgery/diagnostic imaging/complications ; Treatment Outcome ; Risk Factors ; Risk Assessment ; *Stroke/etiology/epidemiology ; Time Factors ; Ultrasonography ; Aged, 80 and over ; }, abstract = {OBJECTIVE: The incidence of stroke after on-pump cardiac surgery during the perioperative period can affect up to 2% of patients, and is frequently linked to carotid artery disease. Notably, in patients with significant unilateral carotid artery stenosis of 80%-99%, the risk of stroke reaches 4%. Among individuals undergoing coronary artery bypass grafting (CABG), 3% to 10% exhibit significant carotid artery stenosis. To mitigate the risk of stroke and mortality, patients can undergo either simultaneous or staged carotid endarterectomy and CABG. The aim of this study was to assess whether early postoperative complications, including stroke, following simultaneous CABG/CAE procedures, correlate with morphological attributes of carotid plaque, assessed via contrast-enhanced ultrasound.

METHODS: A single centre retrospective analysis was performed including 62 patients who underwent simultaneous CABG/CEA between 2019 and 2022. Our study excluded patients who underwent staged carotid endarterectomy and CABG procedures, off-pump CABG, or those necessitating urgent CABG. Our analysis focused on patients meeting elective CABG criteria, diagnosed with symptomatic triple-vessel or left main trunk coronary artery disease (CAD), alongside asymptomatic carotid stenosis (a. carotis internae) exceeding 70% or symptomatic ipsilateral carotid stenosis surpassing 50%. The extent of contralateral carotid artery stenosis was not taken into account. Prior to the CEA/CABG procedure, each patient underwent contrast-enhanced ultrasound to assess atherosclerotic lesions, which were classified using Nakamura et al.'s classification. Among the patients, 37.1% exhibited no neovascularisation within the atherosclerotic plaque, 56.5% showed insignificant neovascularisation, and 6.5% displayed notable neovascularization within the plaque. Our study aimed to establish a connection between the degree of plaque vascularisation identified through contrast-enhanced ultrasound and subsequent postoperative complications.

RESULTS: Upon evaluating postoperative complications occurring within 30 days after the surgery and the plaque morphology identified through contrast-enhanced ultrasound, a statistically significant correlation was observed between a higher grade of plaque vascularisation and the occurrence of ischaemic stroke (r = 0.329, p = .008). Monte Carlo calculations of the Chi-square test indicated a significant association between a higher grade of plaque vascularisation and the presence of peripheral artery disease (χ2 = 15.175, lls = 2, p = .003).

CONCLUSION: Within 30 days of surgery, a significant correlation exists between the occurrence of ischaemic stroke following carotid endarterectomy subsequent to CABG and the presence of a higher grade plaque vascularisation as identified by contrast-enhanced ultrasound.}, } @article {pmid38471312, year = {2024}, author = {Lorenc, T and Stokes, G and Fulbright, H and Sutcliffe, K and Sowden, A}, title = {Communicating cardiovascular risk: Systematic review of qualitative evidence.}, journal = {Patient education and counseling}, volume = {123}, number = {}, pages = {108231}, doi = {10.1016/j.pec.2024.108231}, pmid = {38471312}, issn = {1873-5134}, mesh = {Humans ; *Communication ; *Qualitative Research ; *Cardiovascular Diseases/prevention & control ; Risk Assessment ; Decision Making ; Physician-Patient Relations ; Heart Disease Risk Factors ; Risk Factors ; }, abstract = {INTRODUCTION: Cardiovascular risk prediction models are widely used to help individuals understand risk and make decisions.

METHODS: Systematic review of qualitative evidence. We searched MEDLINE, Embase, PsycINFO and CINAHL. We included English-language qualitative studies on the communication of cardiovascular risk. We assessed study quality using Hawker et al.'s tool and synthesised data thematically.

RESULTS: Thirty-seven studies were included. Many patients think that risk scores are of limited practical value. Other sources of information feed into informal estimates of risk, which may lead patients to reject the results of clinical risk assessment when the two conflict. Clinicians identify a number of barriers to risk communication, including patients' limited understanding of risk and excessive anxiety. They use a range of strategies for adapting risk communication. Both clinicians and individuals express specific preferences for risk communication formats.

DISCUSSION: Ways of communicating risk that provide some comparison or reference point seem more promising. The broader context of communication around risk may be more important than the risk scoring instrument. Risk communication interventions, in practice, may be more about appeals to emotion than a rationalistic model of decision-making.}, } @article {pmid38459406, year = {2024}, author = {Yamamori, Y and Robinson, OJ}, title = {Thinking computationally in translational psychiatry. A commentary on Neville et al. (2024).}, journal = {Cognitive, affective & behavioral neuroscience}, volume = {24}, number = {2}, pages = {384-387}, pmid = {38459406}, issn = {1531-135X}, support = {/WT_/Wellcome Trust/United Kingdom ; 222268/Z/20/Z/WT_/Wellcome Trust/United Kingdom ; MR/R020817/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Humans ; *Translational Research, Biomedical/methods ; Animals ; Mental Disorders ; Psychiatry/methods/trends ; Thinking/physiology ; Reinforcement, Psychology ; Disease Models, Animal ; }, abstract = {There is a growing focus on the computational aspects of psychiatric disorders in humans. This idea also is gaining traction in nonhuman animal studies. Commenting on a new comprehensive overview of the benefits of applying this approach in translational research by Neville et al. (Cognitive Affective & Behavioral Neuroscience 1-14, 2024), we discuss the implications for translational model validity within this framework. We argue that thinking computationally in translational psychiatry calls for a change in the way that we evaluate animal models of human psychiatric processes, with a shift in focus towards symptom-producing computations rather than the symptoms themselves. Further, in line with Neville et al.'s adoption of the reinforcement learning framework to model animal behaviour, we illustrate how this approach can be applied beyond simple decision-making paradigms to model more naturalistic behaviours.}, } @article {pmid38455738, year = {2024}, author = {Klumb, C and Morris, M and Goodreau, SM and Jenness, SM}, title = {Improving and Extending STERGM Approximations Based on Cross-Sectional Data and Tie Durations.}, journal = {Journal of computational and graphical statistics : a joint publication of American Statistical Association, Institute of Mathematical Statistics, Interface Foundation of North America}, volume = {33}, number = {1}, pages = {166-180}, pmid = {38455738}, issn = {1061-8600}, support = {P2C HD042828/HD/NICHD NIH HHS/United States ; R01 AI138783/AI/NIAID NIH HHS/United States ; R24 HD042828/HD/NICHD NIH HHS/United States ; }, abstract = {Temporal exponential-family random graph models (TERGMs) are a flexible class of models for network ties that change over time. Separable TERGMs (STERGMs) are a subclass of TERGMs in which the dynamics of tie formation and dissolution can be separated within each discrete time step and may depend on different factors. The Carnegie et al. (2015) approximation improves estimation efficiency for a subclass of STERGMs, allowing them to be reliably estimated from inexpensive cross-sectional study designs. This approximation adapts to cross-sectional data by attempting to construct a STERGM with two specific properties: a cross-sectional equilibrium distribution defined by an exponential-family random graph model (ERGM) for the network structure, and geometric tie duration distributions defined by constant hazards for tie dissolution. In this paper we focus on approaches for improving the behavior of the Carnegie et al. approximation and increasing its scope of application. We begin with Carnegie et al.'s observation that the exact result is tractable when the ERGM is dyad-independent, and then show that taking the sparse limit of the exact result leads to a different approximation than the one they presented. We show that the new approximation outperforms theirs for sparse, dyad-independent models, and observe that the errors tend to increase with the strength of dependence for dyad-dependent models. We then develop theoretical results in the dyad-dependent case, showing that when the ERGM is allowed to have arbitrary dyad-dependent terms and some dyad-dependent constraints, both the old and new approximations are asymptotically exact as the size of the STERGM time step goes to zero. We note that the continuous-time limit of the discrete-time approximations has the desired cross-sectional equilibrium distribution and exponential tie duration distributions with the desired means. We show that our results extend to hypergraphs, and we propose an extension of the Carnegie et al. framework to dissolution hazards that depend on tie age.}, } @article {pmid38447803, year = {2024}, author = {Porter, L and Sultan, O and Mitchell, BG and Jenney, A and Kiernan, M and Brewster, DJ and Russo, PL}, title = {How long do nosocomial pathogens persist on inanimate surfaces? A scoping review.}, journal = {The Journal of hospital infection}, volume = {147}, number = {}, pages = {25-31}, doi = {10.1016/j.jhin.2024.01.023}, pmid = {38447803}, issn = {1532-2939}, mesh = {Humans ; *Bacteria/classification/isolation & purification ; *Cross Infection/prevention & control/microbiology ; Environmental Microbiology ; *Fungi/isolation & purification/classification ; Time Factors ; Viruses/classification/isolation & purification/pathogenicity ; }, abstract = {Healthcare hygiene plays a crucial role in the prevention of healthcare-associated infections. Patients admitted to a room where the previous occupant had a multi-drug-resistant bacterial infection are at an increased risk of colonization and infection with the same organism. A 2006 systematic review by Kramer et al. found that certain pathogens can survive for months on dry surfaces. The aim of this review is to update Kramer et al.'s previous review and provide contemporary data on the survival of pathogens relevant to the healthcare environment. We systematically searched Ovid MEDLINE, CINAHL and Scopus databases for studies that described the survival time of common nosocomial pathogens in the environment. Pathogens included in the review were bacterial, viral, and fungal. Studies were independently screened against predetermined inclusion/exclusion criteria by two researchers. Conflicts were resolved by one of two senior researchers. A spreadsheet was developed for the data extraction. The search identified 1736 studies. Following removal of duplicates and application of the search criteria, the synthesis of results from 62 included studies were included. 117 organisms were reported. The longest surviving organism reported was Klebsiella pneumoniae which was found to have persisted for 600 days. Common pathogens of concern to infection prevention and control, can survive or persist on inanimate surfaces for months. This data supports the need for a risk-based approach to cleaning and disinfection practices, accompanied by appropriate training, audit and feedback which are proven to be effective when adopted in a 'bundle' approach.}, } @article {pmid38441750, year = {2024}, author = {Bu, F and Arshad, F and Hripcsak, G and Ryan, PB and Schuemie, MJ and Suchard, MA}, title = {Authors' Response to Huang et al.'s Comment on "Serially Combining Epidemiological Designs Does Not Improve Overall Signal Detection in Vaccine Safety Surveillance".}, journal = {Drug safety}, volume = {47}, number = {4}, pages = {403-404}, pmid = {38441750}, issn = {1179-1942}, } @article {pmid38439717, year = {2024}, author = {Cook, D and Hauxwell, C}, title = {Providing rigor in bee colony strength auditing methods.}, journal = {Journal of economic entomology}, volume = {117}, number = {2}, pages = {410-416}, pmid = {38439717}, issn = {1938-291X}, support = {//Hort Frontiers Pollination Fund/ ; //Hort Innovation/ ; //Queensland University of Technology/ ; //Australian Government/ ; }, mesh = {Bees ; Animals ; *Hymenoptera ; Pollination ; *Prunus dulcis ; }, abstract = {The primary method used to audit honey bee (Apis mellifera Linnaeus, 1758 [Hymenoptera: Apidae]) colony strength for almond pollination services, Nasr et al.'s (1990) frame-top cluster count method, is a subjective visual audit that relies on an auditor's spot assessment and may lack rigor and repeatability. We created novel, open-source software for the analysis of frame-top cluster count photographic assessments to improve methodological rigor and repeatability. We evaluated 2 existing visual audit methods, created 3 novel audit method variations, and determined between-method conversion factors using linear modeling. The software has potential applications in apiological research, apiarist and orchardist colony auditing, as well as training future generations of apiarists in auditing techniques. The software enhances the rigor and repeatability of Nasr et al.'s (1990) frame-top cluster count population assessment. In this article, we introduce the novel open-source software and between-method regression equations and review the tested visual assessment methods and their application.}, } @article {pmid38437421, year = {2024}, author = {Qin, W and Fu, Q and Zhang, Y and Zhang, B and Wang, P and Poon, TC and Gu, X}, title = {Rendering of 3D scenes in analytical polygon-based computer holography with texture mapping.}, journal = {Journal of the Optical Society of America. A, Optics, image science, and vision}, volume = {41}, number = {3}, pages = {A32-A39}, doi = {10.1364/JOSAA.507221}, pmid = {38437421}, issn = {1520-8532}, abstract = {A computer-generated hologram (CGH) is a technique that generates an object light field by superimposing elementary holograms. Unlike traditional holography, this technique does not require the generation of an additional reference light to interfere with the calculated object light field. Texture mapping is a method that enhances the realism of 3D scenes. A fast method is presented that allows users to render holograms of 3D scenes consisting of triangular meshes with texture mapping. All calculations are performed with analytical expressions to ensure that the holograms generated by this method are fast and can reconstruct three-dimensional scenes with high quality. Using this method, a hologram of a three-dimensional scene consisting of thousands of triangles is generated. Our algorithm generates the same reconstruction results as those of Kim et al. [Appl. Opt.47, D117 (2008)APOPAI0003-693510.1364/AO.47.00D117], but significantly reduces the computation time (the computation time of our algorithm is only one-third of that of Kim et al.'s algorithm). The results show that the proposed method is computationally efficient as compared to a previous work. The proposed method is verified by simulations and optical experiments.}, } @article {pmid38433528, year = {2024}, author = {Reichenberger, V and Corona, AP and Ramos, VD and Shakespeare, T and Hameed, S and Penn-Kekana, L and Kuper, H}, title = {Access to primary healthcare services for adults with disabilities in Latin America and the Caribbean: a review and meta-synthesis of qualitative studies.}, journal = {Disability and rehabilitation}, volume = {46}, number = {25}, pages = {6011-6020}, pmid = {38433528}, issn = {1464-5165}, support = {MR/R022755/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Adult ; Humans ; Caribbean Region ; *Persons with Disabilities/statistics & numerical data ; *Health Services Accessibility/standards/statistics & numerical data ; Latin America ; *Primary Health Care ; Qualitative Research ; }, abstract = {PURPOSE: This review and meta-synthesis of qualitative studies aims to provide an overview of qualitative evidence on primary healthcare access of people with disability in Latin America and the Caribbean, as well as to identify barriers that exist in this region.

METHODS: Six databases were searched for studies from 2000 to 2022. 34 qualitative studies were identified.

RESULTS: Barriers exist on both demand and supply sides. The thematic synthesis process generated three broad overarching analytical themes, which authors have related to Levesque et al.'s aspects of "ability to perceive," "availability, accommodation and ability to reach" and "appropriateness and ability to engage." Access to information and health literacy are compromised due to a lack of tailored health education materials. Barriers in the urban environment, including inadequate transportation, and insufficient healthcare facility accessibility create challenges for people with disabilities to reach healthcare facilities independently. Attitudinal barriers contribute to suboptimal care experiences.

CONCLUSION: People with disabilities face several barriers in accessing healthcare. Lack of healthcare provider training, inappropriate urban infrastructure, lack of accessible transport and inaccessibility in healthcare centers are barriers that need to be addressed. With these actions, people with disabilities will be closer to having their rights met.}, } @article {pmid38430252, year = {2024}, author = {Carson, HJ and Bobrownicki, R}, title = {Advancing mental imagery research from an interdisciplinary sport science perspective: a commentary on Frank et al. (2023).}, journal = {Psychological research}, volume = {88}, number = {6}, pages = {1833-1836}, pmid = {38430252}, issn = {1430-2772}, mesh = {Humans ; *Imagination/physiology ; Sports/psychology ; Interdisciplinary Research ; Athletes/psychology ; Psychology, Sports ; }, abstract = {Frank et al.'s (2023) perceptual-cognitive scaffold meaningfully extends the cognitive action architecture approach and we support this interdisciplinary advancement. However, there are theoretical and applied aspects that could be further developed within this research to maximise practical impact across domains such as sport. In particular, there is a need to consider how these mechanisms (1) might critically inform or relate to other prominent theories within sport (e.g., constrained action hypothesis and ecological approaches) and, (2) reflect the real-world challenges experienced by athletes. With these ideas in mind, this commentary aims to stimulate discussion and enhance the translational application of Frank et al.'s research.}, } @article {pmid38419098, year = {2024}, author = {Abraham, K and Kvamme, I and Magrin Sammut, S and de Vries, S and Formosa, T and Dupree, R and Corro Ramos, I and Goettsch, W and Franken, M}, title = {A blueprint for health technology assessment capacity building: lessons learned from Malta.}, journal = {International journal of technology assessment in health care}, volume = {40}, number = {1}, pages = {e11}, pmid = {38419098}, issn = {1471-6348}, mesh = {Humans ; *Technology Assessment, Biomedical ; Malta ; *Capacity Building ; Cost-Benefit Analysis ; Knowledge ; }, abstract = {OBJECTIVES: The development and strengthening of health technology assessment (HTA) capacity on the individual and organizational level and the wider environment is relevant for cooperation on HTAs. Based on the Maltese case, we provide a blueprint for building HTA capacity.

METHODS: A set of activities were developed based on Pichler et al.'s framework and the starting HTA capacity in Malta. Individual level activities focused on strengthening epidemiological and health economic skills through online and in-person training. On the organizational level, a new HTA framework was developed which was subsequently utilized in a shadow assessment. Awareness campaign activities raised awareness and support in the wider environment where HTAs are conducted and utilized.

RESULTS: The time needed to build HTA capacity exceeded the planned two years accommodating the learning progress of the assessors. In addition to the planned trainings, webinars supplemented the online courses, allowing for more knowledge exchange. The advanced online course was extended over time to facilitate learning next to the assessors' daily tasks. Training sessions were added to implement the new economic evaluation framework, which was utilized in a second shadow assessment. Awareness by decision-makers was achieved with reports, posters, and an article on the current and developing HTA capacity.

CONCLUSIONS: It takes time and much (hands-on) training to build skills for conducting complex assessment such as HTAs. Facilitating exchange with knowledgeable parties is crucial for succeeding as well as the buy-in of local managers motivating staff. Decision-makers need to be on-boarded for the continued success of HTA capacity building.}, } @article {pmid38415397, year = {2024}, author = {Miller, KN and Bourne, SV and Dahl, CM and Costello, C and Attinelly, J and Jennings, K and Dozier, M}, title = {Using randomized controlled trials to ask questions regarding developmental psychopathology: A tribute to Dante Cicchetti.}, journal = {Development and psychopathology}, volume = {36}, number = {5}, pages = {2305-2314}, pmid = {38415397}, issn = {1469-2198}, support = {R01 MH074374/MH/NIMH NIH HHS/United States ; }, mesh = {Humans ; Female ; Adolescent ; Male ; *Mother-Child Relations/psychology ; *Object Attachment ; *Parenting/psychology ; Randomized Controlled Trials as Topic ; Mothers/psychology ; Psychotherapy/methods ; Child ; }, abstract = {Dante Cicchetti, the architect of developmental psychopathology, has influenced so many of us in profound ways. One of his many contributions was in demonstrating the power of randomized controlled trials (RCTs) to study the effects of Child-Parent Psychotherapy (CPP). These RCTs have shed light on causal mechanisms in development. Following Cicchetti and colleagues' work, we designed a brief home visiting program, Attachment and Biobehavioral Catch-up (ABC), to help parents respond in sensitive, nurturing ways, so as to enhance children's attachment and self-regulatory capabilities. In the current study, we assessed adolescents' reports of the closeness of their relationships with their mothers 12 years after their mothers completed the intervention. A total of 142 adolescents participated (47 randomized to ABC, 45 randomized to a control intervention, and 50 from a low-risk comparison group). Adolescents whose mothers had been randomized to ABC reported closer relationships with their mothers than adolescents randomized to the control condition, with significant differences seen on approval, support, companionship, and emotional support subscales. Consistent with Cicchetti et al.'s work, these results provide powerful evidence of the long-term effects of an early parenting intervention.}, } @article {pmid38411036, year = {2025}, author = {Douglas, RD and Alli, JO and Gaylord-Harden, N and Opara, I and Gilreath, T}, title = {Examining the integrated model of the interpersonal-psychological theory of suicide and intersectionality theory among Black male adolescents.}, journal = {Suicide & life-threatening behavior}, volume = {55}, number = {1}, pages = {e13066}, pmid = {38411036}, issn = {1943-278X}, support = {DP1 DA058982/DA/NIDA NIH HHS/United States ; DP5 OD029636/OD/NIH HHS/United States ; L60 DA054692/DA/NIDA NIH HHS/United States ; }, mesh = {Adolescent ; Humans ; Male ; *Black or African American/psychology ; Interpersonal Relations ; Models, Psychological ; Poverty/psychology ; *Psychological Theory ; *Racism/psychology ; *Suicidal Ideation ; Suicide/psychology/ethnology ; Violence/psychology ; }, abstract = {INTRODUCTION: Guided by Opara et al.'s (2022), Integrated Model of the Interpersonal Psychological Theory of Suicide and Intersectionality Theory, the current study examined contextual stressors experienced disparately by Black youth (racial discrimination, poverty, and community violence) as moderators of the association between individual motivating factors for suicidal thoughts and behaviors (perceived burdensomeness, thwarted belongingness, and hopelessness) and active suicidal ideation.

METHOD: Participants were 457 Black adolescent boys (mean age = 15.31, SD = 1.26) who completed self-report surveys.

RESULTS: As predicted, the association between perceived burdensomeness and active suicidal ideation was significantly moderated by economic stress. In addition, the association between peer belongingness and suicidal ideation was significantly moderated by racial discrimination, but there were no moderating effects for school belongingness. Finally, the association between hopelessness and suicidal ideation was significantly moderated by both racial discrimination and witnessing community violence.

CONCLUSION: These findings highlight the need for research, interventions, and policy work devoted to using integrated approaches of individual and socioeconomically relevant patterns of suicidal thoughts and behaviors to support Black youth exposed to various forms of structural oppression.}, } @article {pmid38402380, year = {2024}, author = {Stefanik-Guizlo, K and Allen, C and Brush, S and Mogk, J and Canada, S and Peck, M and Ramos, K and Volpe, K and Lozano, P}, title = {Sustaining connections: feasibility and impact of long-term virtual patient engagement.}, journal = {Research involvement and engagement}, volume = {10}, number = {1}, pages = {28}, pmid = {38402380}, issn = {2056-7529}, abstract = {BACKGROUND: Virtual patient engagement has become more common in recent years. Emerging research suggests virtual engagement can increase accessibility for patients managing long-term health conditions and those living in larger geographic areas, but it can also be challenging to establish relationships and maintain engagement over time. Little is known about virtual engagement lasting more than two years, nor about the specific contributions of patients to virtual engagement projects. Here we describe a project where virtual engagement was sustained over a long period of time (3.5 years), measure patients' contributions to the work, and describe the facilitators and challenges of the project using the Valuing All Voices (VAV) patient engagement framework.

METHODS: Five researchers recruited four patient partners living with persistent pain to work together virtually on a project to improve care for others with long-term pain. Researchers documented engagement activities and patient partner contributions and categorized them using Carman et al.'s 3 types of engagement. They also collected data via semi-structured group interviews with patient partners about the facilitators and challenges of the project using the VAV framework.

RESULTS: In 3.5 years, patient partners contributed 487 h to the project, averaging 3.0 h per month, and participated in 40 meetings. They contributed to 17 products for patients, health care teams, and researchers. Most products (12 of 17) were created using the more in-depth engagement approaches of involvement or partnership and shared leadership. The group identified facilitators of the project across the five VAV domains of relationship-building, trust, understanding & acceptance, education & communication, and self-awareness, as well as some specific challenges such as keeping track of products across virtual platforms and managing the high volume of project information.

CONCLUSIONS: Long-term virtual patient engagement is feasible and can use more in-depth engagement approaches. Additionally, it can result in substantial contributions from patients in terms of time, effort, and products. These findings can inform future long-term virtual patient engagement efforts and provide insight into how researchers can structure their activities to encourage and maintain deep engagement over time.}, } @article {pmid38388779, year = {2024}, author = {Friedgen, E and Koch, I and Poljac, E and Liefooghe, B and Stephan, DN}, title = {Voluntary task switching is affected by modality compatibility and preparation.}, journal = {Memory & cognition}, volume = {52}, number = {5}, pages = {1195-1209}, pmid = {38388779}, issn = {1532-5946}, support = {KO2045/19-2//Deutsche Forschungsgemeinschaft/ ; }, mesh = {Humans ; Young Adult ; Adult ; *Psychomotor Performance/physiology ; Male ; Female ; *Executive Function/physiology ; *Auditory Perception/physiology ; Visual Perception/physiology ; Choice Behavior/physiology ; }, abstract = {Cognitive task control can be examined in task-switching studies. Performance costs in task switches are usually smaller with compatible stimulus-response modality mappings (visual-manual and auditory-vocal) than with incompatible mappings (visual-vocal and auditory-manual). Modality compatibility describes the modality match of sensory input and of the anticipated response effect (e.g., vocal responses produce auditory effects, so that auditory stimuli are modality-compatible with vocal responses). Fintor et al. (Psychological Research, 84(2), 380-388, 2020) found that modality compatibility also biased task choice rates in voluntary task switching (VTS). In that study, in each trial participants were presented with a visual or auditory spatial stimulus and were free to choose the response modality (manual vs. vocal). In this free-choice task, participants showed a bias to create more modality-compatible than -incompatible mappings. In the present study, we assessed the generality of Fintor et al.'s (2020) findings, using verbal rather than spatial stimuli, and more complex tasks, featuring an increased number of stimulus-response alternatives. Experiment 1 replicated the task-choice bias to preferentially create modality-compatible mappings. We also found a bias to repeat the response modality just performed, and a bias to repeat entire stimulus-response modality mappings. In Experiment 2, we manipulated the response-stimulus interval (RSI) to examine whether more time for proactive cognitive control would help resolve modality-specific crosstalk in this free-choice paradigm. Long RSIs led to a decreased response-modality repetition bias and mapping repetition bias, but the modality-compatibility bias was unaffected. Together, the findings suggest that modality-specific priming of response modality influences task choice.}, } @article {pmid38369706, year = {2024}, author = {Hautea, S and Besley, JC and Choung, H}, title = {Communicating trust and trustworthiness through scientists' biographies: Benevolence beliefs.}, journal = {Public understanding of science (Bristol, England)}, volume = {33}, number = {7}, pages = {872-883}, doi = {10.1177/09636625241228733}, pmid = {38369706}, issn = {1361-6609}, mesh = {*Trust ; Communication ; Beneficence ; Humans ; Science ; Research Personnel/psychology ; Male ; }, abstract = {A goal of many science communicators is to foster trust in scientists and their work. This study investigates if existing textual resources that scientists create in the course of their regular activities can be improved to enhance perceptions of scientists as trustworthy. Building on Mayer et al.'s integrative model of organizational trust, we examine how communicating benevolence through short biographies can affect trustworthiness perceptions using a 3 (degree of benevolence information: high, unspecified, low) × 3 (research area: crop genetics, corn and soy genetics, biotechnology use) survey design. We find that the degree of benevolence information significantly influences perceptions of benevolence and integrity, as well as willingness to trust, with these effects being consistent across different research areas. However, the degree of benevolence communicated had no significant effect on the perceived competence of the scientists. These findings underscore the importance of highlighting benevolence in communication to positively influence trustworthiness perceptions, thus offering insights for science communication practices.}, } @article {pmid38368678, year = {2024}, author = {Pachur, T}, title = {The perception of dramatic risks: Biased media, but unbiased minds.}, journal = {Cognition}, volume = {246}, number = {}, pages = {105736}, doi = {10.1016/j.cognition.2024.105736}, pmid = {38368678}, issn = {1873-7838}, mesh = {Humans ; *Judgment ; *Mass Media ; Bayes Theorem ; Risk ; Adult ; }, abstract = {In their famous study on risk judgments, Lichtenstein, Slovic, Fischhoff, Layman, and Combs (1978) concluded that people tend to overestimate the frequencies of dramatic causes of death (e.g., homicide, tornado) and underestimate the frequencies of nondramatic ones (e.g., diabetes, heart disease). Further, their analyses of newspapers indicated that dramatic risks are overrepresented in the media-suggesting that people's distorted risk perceptions might be driven by distortions in media coverage. Although these patterns were not evaluated statistically in the original analyses, the conclusions have become a staple in the social sciences. How reliable are they? And are they replicable? In a systematic literature search, I identified existing replications of Lichtenstein et al.'s investigation and submitted both the original data and the data from the replications to a Bayesian statistical analysis. All datasets indicated very strong evidence for an overrepresentation of dramatic risks and an underrepresentation of nondramatic risks in media coverage. However, a reliable overestimation (underestimation) of dramatic (nondramatic) risks in people's frequency judgments emerged only in Lichtenstein et al.'s dataset; it did not replicate in the other datasets. In fact, aggregated across all datasets, there was evidence for the absence of a differential distortion of dramatic and nondramatic causes of death in people's risk frequency judgments. Additional analyses suggest that when judging risk frequency, people rely on samples from their personal social networks rather than from the media. The results reveal a limited empirical basis for the common notion that distortions in people's risk judgments echo distortions in media coverage. They also suggest that processes of risk frequency judgments include a metacognitive mechanism that is sensitive to the source of mentally available samples.}, } @article {pmid38364750, year = {2024}, author = {Mercier, A and Dorris, L}, title = {A systematic review of psychosocial interventions for children and young people with epilepsy.}, journal = {European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society}, volume = {49}, number = {}, pages = {35-44}, doi = {10.1016/j.ejpn.2024.02.002}, pmid = {38364750}, issn = {1532-2130}, mesh = {Adolescent ; Child ; Humans ; *Epilepsy/psychology/therapy ; *Psychosocial Intervention/methods ; Quality of Life/psychology ; }, abstract = {BACKGROUND: Epilepsy is a lifelong neurological disorder that has a profound impact on the lives of millions of children and young people throughout the world, and is linked with mental ill-health and a poorer quality of life. Psychosocial interventions have showed promise for children and young people with epilepsy (CYPE), however there is an absence of large-scale RCT's that would add robustness to the evidence base. The present systematic review provides an update and extension of findings from an earlier review by Corrigan et al. to assess the state of the literature in 2023.

METHODS: The present systematic review carried out a search of six electronic databases. Forward and backward chaining was carried out on review articles as well as the studies returned through the search to source additional studies. In total, ten articles were included in this review and appraised for quality using the Crowe Critical Appraisal Tool (CCAT).

RESULTS: Forty percent (4/10) of the included studies were rated as high quality according to the CCAT, which represents a significant proportional increase since Corrigan et al.'s review. A meta-analysis of results was not possible due to significant methodological heterogeneity, and the variability of outcome measures, however effect sizes were reported or calculated for the majority of studies (7/10), which facilitated comparison. Despite the issues of relatively small samples, there are promising findings with regard to psychosocial interventions increasing epilepsy knowledge, coping strategies, self-efficacy, and quality of life markers.

CONCLUSIONS: There is a growing evidence base supporting the efficacy of psychosocial interventions for children and young people with epilepsy. This evidence base is also increasing in quality. Particular components of treatment that prove to be effective include psychoeducation, components based on cognitive behavioural therapy principles, as well as mindfulness techniques. This aligns with the evidence-based recommendations for adult populations. Intervention goals centre around improving quality of life, reducing symptom distress, and increasing knowledge and skills. The instruments used to measure these outcomes are predominantly standardised, however remain heterogeneous between studies which impacts the overall robustness of the evidence base.}, } @article {pmid38361279, year = {2024}, author = {Wu, W and Meng, Y and Tsauo, C and Chen, M and Huang, D and Zhou, X and Zou, L and Gao, Y}, title = {Internal and external morphological analysis of fused-rooted mandibular second molars in the Chinese population: A micro-computed tomographic study.}, journal = {Australian endodontic journal : the journal of the Australian Society of Endodontology Inc}, volume = {50}, number = {2}, pages = {285-298}, doi = {10.1111/aej.12833}, pmid = {38361279}, issn = {1747-4477}, support = {2023NSFSC0554//Science & Technology Department of Sichuan Province/ ; 62171193//National Natural Science Foundation of China/ ; 62373263//National Natural Science Foundation of China/ ; }, mesh = {Humans ; China ; *Dental Pulp Cavity/anatomy & histology/diagnostic imaging ; East Asian People ; Fused Teeth/diagnostic imaging ; *Mandible/anatomy & histology/diagnostic imaging ; *Molar/anatomy & histology/diagnostic imaging ; *Tooth Root/anatomy & histology/diagnostic imaging ; *X-Ray Microtomography/methods ; }, abstract = {This study investigated the root canal morphology of fused-rooted mandibular second molars based on the pulp chamber floor (PCF) and analysed the correlation between the external morphology of the radicular groove, and the internal morphology of the PCF and root canal configuration. A total of 291 fused-rooted teeth collected from the Chinese population were scanned using micro-computed tomography and a dental operating microscope was used for observing the PCFs. The classification of the PCF and root canal configuration were identified according to modified Min et al.'s and Gao et al.'s classifications, respectively. Additionally, a new radicular groove classification was proposed. The correlation among these morphological characteristics was investigated using the chi-square test and Fisher's exact test (p < 0.05). The results showed that 74.2% of teeth had C-shaped PCFs, while 21.0% had non-C-shaped PCFs. As for the root canal configurations, 37.5% of teeth were merging type, 40.9% were symmetrical type, and 14.8% were asymmetrical type. Statistical analysis revealed a significant correlation between the PCF types and the root canal configurations (p < 0.001). The dominant root canal types for teeth with C-shaped PCFs were merging and symmetrical types, while the asymmetrical type was not identified in non-C-shaped PCFs. In addition, significant morphological association between the root canals and radicular grooves was also revealed (p < 0.001). Teeth with different PCF morphologies exhibit specific patterns of root canal category distribution. Understanding the morphological nuances of the root canal based on the PCF can assist clinicians in predicting and identifying the canal configuration beneath the visible orifice.}, } @article {pmid38361250, year = {2024}, author = {Wu, T and Weiland, C and McCormick, M and Hsueh, J and Snow, C and Sachs, J}, title = {One Score to Rule Them All? Comparing the Predictive and Concurrent Validity of 30 Hearts and Flowers Scoring Approaches.}, journal = {Assessment}, volume = {31}, number = {8}, pages = {1702-1720}, doi = {10.1177/10731911241229566}, pmid = {38361250}, issn = {1552-3489}, mesh = {Humans ; Male ; Female ; *Executive Function ; Reproducibility of Results ; Child ; Child, Preschool ; Reaction Time ; Neuropsychological Tests ; }, abstract = {The Hearts and Flowers (H&F) task is a computerized executive functioning (EF) assessment that has been used to measure EF from early childhood to adulthood. It provides data on accuracy and reaction time (RT) across three different task blocks (hearts, flowers, and mixed). However, there is a lack of consensus in the field on how to score the task that makes it difficult to interpret findings across studies. The current study, which includes a demographically diverse population of kindergarteners from Boston Public Schools (N = 946), compares the predictive and concurrent validity of 30 ways of scoring H&F, each with a different combination of accuracy, RT, and task block(s). Our exploratory results provide evidence supporting the use of a two-vector average score based on Zelazo et al.'s approach of adding accuracy and RT scores together only after individuals pass a certain accuracy threshold. Findings have implications for scoring future tablet-based developmental assessments.}, } @article {pmid38360549, year = {2024}, author = {Higdon, KF and Neath, I and Surprenant, AM and Ensor, TM}, title = {Distinctiveness, not dual coding, explains the picture-superiority effect.}, journal = {Quarterly journal of experimental psychology (2006)}, volume = {}, number = {}, pages = {17470218241235520}, doi = {10.1177/17470218241235520}, pmid = {38360549}, issn = {1747-0226}, abstract = {The picture-superiority effect is the finding that memory for pictures exceeds memory for words on many tasks. According to dual-coding theory, the pictures' mnemonic advantage stems from their greater likelihood to be labelled relative to words being imaged. In contrast, distinctiveness accounts hold that the greater variability of pictures compared to words leads to their mnemonic advantage. Ensor, Surprenant, et al. tested these accounts in old/new and forced-choice recognition by increasing the physical distinctiveness of words and decreasing the physical distinctiveness of pictures. Half of the words were presented in standard black font, and half were presented in varying font styles, font sizes, font colours, and capitalisation patterns. Half of the pictures were presented in black and white and half in colour. Consistent with the physical-distinctiveness account but contrary to the dual-coding account, the picture-superiority effect was eliminated when comparing the black-and-white pictures to distinctive words. In the present study, we extend Ensor, Surprenant, et al.'s results to associative recognition and free recall. Results were consistent with physical distinctiveness. We argue that dual-coding theory is no longer a viable explanation of the picture-superiority effect.}, } @article {pmid38355728, year = {2024}, author = {Lin, YH and Juang, HH}, title = {Influence of anterior fibromuscular stroma on incontinence outcomes in RASP and HoLEP: a critical analysis of Grosso et al.'s findings.}, journal = {Prostate cancer and prostatic diseases}, volume = {27}, number = {3}, pages = {573-574}, pmid = {38355728}, issn = {1476-5608}, mesh = {Humans ; Male ; *Urinary Incontinence/etiology ; Prostatectomy/methods/adverse effects ; Treatment Outcome ; Robotic Surgical Procedures/methods ; Prostatic Hyperplasia/surgery/pathology ; }, } @article {pmid38355335, year = {2024}, author = {Eyni, S and Mousavi, SE and Sepahvand, H}, title = {Acceptance of Chronic Pain in Cancer Patients in Iran: the Role of Anxiety Sensitivity, Emotional Suppression, and Learned Helplessness.}, journal = {Pain management nursing : official journal of the American Society of Pain Management Nurses}, volume = {25}, number = {2}, pages = {e144-e151}, doi = {10.1016/j.pmn.2023.12.012}, pmid = {38355335}, issn = {1532-8635}, mesh = {Humans ; *Chronic Pain/complications ; Helplessness, Learned ; Iran ; *Cancer Pain ; Anxiety/etiology/psychology ; *Neoplasms/complications ; }, abstract = {BACKGROUND: Acceptance of pain is one of the most significant topics in the field of chronic pain due to its influence on the adaptation and response of people. Also, chronic pain and pain caused by the progress of cancer have a high prevalence in all stages and types of cancer.

AIMS: The present study aimed to predict the acceptance of chronic pain in patients with cancer based on anxiety sensitivity and emotional suppression with the mediating role of learned helplessness.

METHODS: The current research method was descriptive-correlation and structural equation modeling. A number of patients with cancer (400), admitted to the oncology department of Imam Khomeini Hospital in Ardabil City of Iran in the second half of 2022, were selected as the convenience sample and responded to McCracker et al.'s chronic pain acceptance scale, Rees et al.'s anxiety sensitivity scale, Roger and Nasho's emotional control questionnaire, and Quinles and Nielson's learned helplessness questionnaire.

RESULTS: Based on the obtained results, the causal relationship between anxiety sensitivity, emotional suppression, learned helplessness, and acceptance of chronic pain in patients with cancer was confirmed based on various fit indices. Anxiety sensitivity, emotional suppression, and learned helplessness had a direct effect on the acceptance of chronic pain in patients with cancer. Moreover, anxiety sensitivity and emotional suppression through learned helplessness had indirect effects on pain acceptance in patients with cancer (p < .05).

CONCLUSIONS: Thus, anxiety sensitivity, emotional suppression, and learned helplessness play an essential role in the level of pain acceptance in patients with cancer, and targeting these three components through psychological treatments can be effective in the level of pain acceptance in these patients.}, } @article {pmid38351700, year = {2024}, author = {Piredda, M and Gambalunga, F and Enrico, SM and Mangado, R and D'Angelo, AG and Marchetti, A and Mastroianni, C and Iacorossi, L and De Marinis, MG}, title = {Nurses' experiences of caring for nursing care-dependent ICU patients: A qualitative study.}, journal = {Nursing in critical care}, volume = {29}, number = {5}, pages = {896-904}, doi = {10.1111/nicc.13047}, pmid = {38351700}, issn = {1478-5153}, mesh = {Qualitative Research ; Focus Groups ; *Nurse-Patient Relations ; *Intensive Care Units ; *Critical Care Nursing ; Humans ; Male ; Female ; Adult ; Middle Aged ; Time Factors ; Trust/psychology ; Empathy ; Attitude of Health Personnel ; *Nursing Staff, Hospital/psychology ; }, abstract = {BACKGROUND: Nursing care dependency is a key, yet under-studied, nursing phenomenon. Patients in intensive care units are highly dependent on nursing care. Patients find dependency challenging, experiencing feelings of powerlessness and shame. The nurse-patient care relationship can influence patients' perception of dependency. Understanding how nurses experience their care for dependent patients is crucial, as nurses might not always grasp the impact of their actions on patients' dependency experiences.

AIM: To explore and interpret ICU nurses' perceptions of patients' nursing care dependency and their experiences in caring for nursing care-dependent patients.

STUDY DESIGN: A qualitative interpretative phenomenological study inspired by Merleau-Ponty's philosophical stance was conducted using focus groups with nurses who had been caring for adult patients for at least 6 months in ICUs of two hospitals. Data analysis followed Smith et al.'s guidance. Researchers immersed themselves in the transcripts, noted individual's experiences before transitioning to shared insights, coded significant phrases and generated themes and superordinate themes.

RESULTS: Four focus groups were conducted with 18 nurses with widely ranging ages and work experience. Four superordinate themes emerged: 'Time and context define dependency', 'Empathetic relationships help nurses understand patients' experience of dependency', 'Trusting nurse-patient relationships change the dependency experience' and 'Nurses' skills help patients to recover independence'.

CONCLUSION: This study increases critical care nurses' awareness of the overlooked phenomenon of caring for nursing care dependent patients and offers them an opportunity to reflect on their care for dependent patients and adapt it to patients' experiences. Further studies are needed with nurses and patients in different ICUs, cultures and countries, to gain a broader picture of experiences of nursing care dependency.

ICU nurses need strong relational skills to offer high-quality care for dependent patients, facilitating meaningful nurse-patient relationships based on empathy and trust. These relationships can significantly impact the patient's experience of dependence.}, } @article {pmid38345481, year = {2024}, author = {De Laet, J and Goloboff, PA}, title = {Nothing to it: a reply to Wheeler's "much ado about nothing".}, journal = {Cladistics : the international journal of the Willi Hennig Society}, volume = {40}, number = {4}, pages = {456-467}, doi = {10.1111/cla.12571}, pmid = {38345481}, issn = {1096-0031}, support = {PIP 110//Consejo Nacional de Investigaciones Científicas y Técnicas/ ; PIP 11220200102052//Consejo Nacional de Investigaciones Científicas y Técnicas/ ; PUE 0070//Consejo Nacional de Investigaciones Científicas y Técnicas/ ; 2148768//National Science Foundation/ ; }, mesh = {*Phylogeny ; *Algorithms ; }, abstract = {Wheeler (Cladistics 2023, 39, 475) recently suggested that the issues with inapplicable characters in phylogenetic analysis can be dealt with directly by treating observed absences of a feature not in a separate absence/presence character but as insertion/deletion events in a complex character that describes the feature in all its variation; and that this dynamic homology view can be achieved by imposing a sequence or linear order on a set of characters and by analysing the resulting sequence character using custom alphabet tree alignment algorithms. As Wheeler observed, this approach can lead to considering inappropriate character states (such as a head state and a foot state) homologous. We show that it is also sensitive to the specific ordering assumption used and that such different character orders can lead to a preference for different trees. We present a simple four-taxon dataset with observations of absence, but no inapplicable characters or other kinds of character dependence, for which the dynamic homology framework gives different results to classic algorithms for independent characters, including an optimal tree with biologically impossible reconstructions at inner nodes (every terminal has a head but the inner nodes are headless). We show how these issues can be solved by removing the character ordering assumption that the approach requires. Doing so, the dynamic homology framework reduces in general to Maddison's (Syst. Biol. 1993, 42, 576) well-known proposal to deal with inapplicability using step matrix analysis of complex characters. If in addition costs are interpreted in terms of homology, it reduces to Goloboff et al.'s (Cladistics 2021, 37, 596) step matrix implementation for maximization of homology as applied to inapplicable characters. However, if used with homogeneous costs, as Wheeler suggested, it reduces to unordered analysis of such complex characters, which is known to treat tails that may share many observed features as irrelevant for establishing kinship when they differ in just one feature, e.g. colour.}, } @article {pmid38341094, year = {2024}, author = {McKechnie, T and Brennan, K and Eskicioglu, C and Farooq, A and Patel, SV}, title = {Applying the fragility index to randomized controlled trials evaluating total neoadjuvant therapy for rectal cancer: A methodological survey.}, journal = {Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology}, volume = {194}, number = {}, pages = {110148}, doi = {10.1016/j.radonc.2024.110148}, pmid = {38341094}, issn = {1879-0887}, mesh = {Humans ; *Neoadjuvant Therapy ; Randomized Controlled Trials as Topic ; *Rectal Neoplasms/therapy/pathology ; }, abstract = {BACKGROUND: Recently, there has been significant interest in, and adoption of, total neoadjuvant therapy (TNT) for locally advanced rectal cancer (LARC). We designed the present study to assess the robustness of the randomized controlled trials (RCTs) evaluating contemporary TNTs for LARC using the fragility index (FI).

MATERIALS AND METHODS: Relevant articles were identified through a review article by Johnson et al. in the Canadian Journal of Surgery. Dichotomous outcomes within these RCTs were eligible for inclusion if the reported effect size had a p-value < 0.05. The main outcome was FI for each included outcome. Walsh et al.'s method of calculating FI was utilized. Correlations between FI and research characteristics were assessed using the Spearman's rank correlation coefficients. Risk of bias was assessed using Cochrane recommended tools.

RESULTS: Ten RCTs were identified with 25 outcomes having statistically significant differences between groups. Eleven outcomes were time-to-event outcomes, while the remainder were dichotomous outcomes. Approximately half (n = 13) were oncologic outcomes. The median FI was 2 (interquartile range [IQR] 1-16). The number of patients lost to follow-up exceeded the FI in 17 outcomes (68.0 %) and thus these results were considered "fragile". Lower FI was associated with high risk of bias (rho = -0.5594) and greater loss to follow-up (rho = -0.4394), while higher FI was associated with large study size (rho = 0.5120).

CONCLUSIONS: The robustness of outcomes from trials assessing TNT for LARC was found to be questionable. Most outcomes were fragile, as determined by the FI. This survey is limited by the number of included studies.}, } @article {pmid38339695, year = {2024}, author = {Purnama, H and Mambo, M}, title = {IHIBE: A Hierarchical and Delegated Access Control Mechanism for IoT Environments.}, journal = {Sensors (Basel, Switzerland)}, volume = {24}, number = {3}, pages = {}, pmid = {38339695}, issn = {1424-8220}, abstract = {Ensuring authorized access control in the IoT is vital for privacy and safety protection. Our study presents the novel IHIBE framework, which combines IOTA (a distributed ledger technology) with hierarchical identity-based encryption (HIBE), thereby enhancing both IoT security and scalability. This approach secures access tokens and policies while reducing the computational demand on data owners. Our empirical findings reveal a significant performance gap, with access rights delegation on the Raspberry Pi 4 exceeding those on AWS by over 250%. Moreover, our analysis uncovers optimal identity policy depths: up to 640 identities on AWS and 640 on the Raspberry Pi 4 for systems with higher tolerable delays, and 320 identities on AWS versus 160 on the Raspberry Pi 4 for systems with lower tolerable delays. The system shows practical viability, exhibiting insignificant operational time differences compared to Zhang et al.'s schemes, particularly in access rights verification processes, with a minimal difference of 33.35%. Our extensive security assessment, encompassing scenarios like encrypted token theft and compromise of authority, affirms the efficacy of our challenge-response and last-word challenge (LWC) mechanisms. This study underscores the importance of platform choice in IoT system architectures and provides insights for deploying efficient, secure, and scalable IoT environments.}, } @article {pmid38335614, year = {2024}, author = {Degli-Innocenti, F}, title = {Rebuttal of the arguments put forward in the Letter to the Editor by Nizzetto et al.}, journal = {Journal of hazardous materials}, volume = {467}, number = {}, pages = {133691}, doi = {10.1016/j.jhazmat.2024.133691}, pmid = {38335614}, issn = {1873-3336}, abstract = {In their Letter to the Editor, Nizzetto et al. challange a recent article in which I show that there has been unwarranted alarmism about biodegradable mulch films due to the publication of numerous articles based on preliminary data that are irrelevant for drawing conclusions on environmental risk. The tendency to over-emphasise results in order to attract attention is a growing problem in the scientific world and has been studied by many scholars. Nizzetto et al. accuse me of not using scientific methodology and of not disclosing that I am a scientist working for a company that produces biodegradable plastics. In this rebuttal I show that Nizzetto et al.'s accusations suffer from a number of logical fallacies, in particular the "straw man" fallacy and the "ad hominem" fallacy.}, } @article {pmid38332485, year = {2024}, author = {Alrashdi, DH and Alyafei, AH and Alanazi, SA and Meyer, C and Gould, RL}, title = {Cultural adaptations of third-wave psychotherapies in Gulf Cooperation Council countries: A systematic review.}, journal = {Transcultural psychiatry}, volume = {61}, number = {2}, pages = {209-228}, pmid = {38332485}, issn = {1461-7471}, mesh = {Humans ; *Psychotherapy ; }, abstract = {The effectiveness of third-wave psychotherapies has been demonstrated in a range of mental and physical health conditions in Western cultures. However, little is known about the cultural appropriateness and effectiveness of third-wave psychotherapies for Gulf Cooperation Council (GCC) populations. This review aimed to critically evaluate cultural adaptations to third-wave psychotherapies and explored the effectiveness of these interventions on physical and mental health outcomes in GCC populations. Five bibliographic databases and grey literature were searched; both English and Arabic studies conducted in the GCC were included. Mental and physical health-related outcomes were included. Eleven studies were identified. The overall degree of cultural adaptation ranged from 2 to 5, based on Bernal et al.'s cultural adaptation framework. Language and assessment tools were most frequently adapted. Several studies incorporated goal, method, and context adaptations, whereas metaphor and content were least frequently adapted. None of the studies incorporated person or concept adaptations. Culturally adapted third-wave psychotherapies were associated with improvement in numerous mental health outcomes, including psychological distress, well-being, and psychological traits. No physical health outcomes were identified. Although findings are promising with respect to the effectiveness of third-wave psychotherapies for GCC populations, they should be interpreted with caution due to the small number of studies conducted, cultural adaptation evaluations relying on explicit reporting in studies, and the weak methodological quality of studies. Future rigorous research is needed in the evaluation of culturally adapted third-wave psychotherapies in GCC populations, with more comprehensive reporting of cultural considerations.}, } @article {pmid38323802, year = {2024}, author = {Sharma, R and Chen, C and Tan, L and Rolfe, K and Fiţa, IG and Jones, S and Pingle, A and Gibson, RA and Goyal, N and Sharma, H and Bird, P}, title = {Comment on 'The clinical pharmacology of tafenoquine in the radical cure of Plasmodium vivax malaria: An individual patient data meta-analysis'.}, journal = {eLife}, volume = {13}, number = {}, pages = {}, pmid = {38323802}, issn = {2050-084X}, mesh = {Humans ; *Aminoquinolines ; *Antimalarials/therapeutic use ; Chloroquine/therapeutic use ; *Malaria, Vivax/drug therapy ; Primaquine/therapeutic use ; Meta-Analysis as Topic ; }, abstract = {A single 300 mg dose of tafenoquine, in combination with chloroquine, is currently approved in several countries for the radical cure (prevention of relapse) of Plasmodium vivax malaria in patients aged ≥16 years. Recently, however, Watson et al. suggested that the approved dose of tafenoquine is insufficient for radical cure, and that a higher 450 mg dose could reduce P. vivax recurrences substantially (Watson et al., 2022). In this response, we challenge Watson et al.'s assertion based on empirical evidence from dose-ranging and pivotal studies (published) as well as real-world evidence from post-approval studies (ongoing, therefore currently unpublished). We assert that, collectively, these data confirm that the benefit-risk profile of a single 300 mg dose of tafenoquine, co-administered with chloroquine, for the radical cure of P. vivax malaria in patients who are not G6PD-deficient, continues to be favourable where chloroquine is indicated for P. vivax malaria. If real-world evidence of sub-optimal efficacy in certain regions is observed or dose-optimisation with other blood-stage therapies is required, then well-designed clinical studies assessing safety and efficacy will be required before higher doses are approved for clinical use.}, } @article {pmid38322242, year = {2023}, author = {Serrao, F and Tiberi, E and Verdolotti, T and Romeo, DMM and Corsello, M and Pede, E and Cota, F and Costa, S and Gallini, F and Colosimo, C and Mercuri, EM and Vento, G}, title = {pCO2 values in asphyxiated infants under therapeutic hypothermia after tailored respiratory management: a retrospective cohort study.}, journal = {Frontiers in pediatrics}, volume = {11}, number = {}, pages = {1293526}, pmid = {38322242}, issn = {2296-2360}, abstract = {BACKGROUND: Hypoxic-ischemic encephalopathy (HIE) represents one of the major causes of neonatal death and long-term neurological disability. Both hypoxic-ischemic insults and therapeutic hypothermia (TH) can affect respiratory function. Currently, there is no evidence regarding optimal respiratory management in these infants.

METHODS: This is a retrospective cohort study examining newborns with HIE treated with TH between January 2015 and September 2020. The study population was divided into two groups based on different respiratory assistance during TH: spontaneous breathing (Group A) or mechanical ventilation (Group B). The primary outcome of the study was the mean pCO2 ± SD evaluation during TH in ventilated and non-ventilated asphyxiated infants. The secondary outcome was the correlation between ventilation strategy and short-term neurologic outcome according to Rutherford et al.'s MRI scoring system.

RESULTS: A total of 126 newborns were enrolled, 75 in Group A and 51 in Group B. Respiratory management was individualized, and volume guarantee (VG) ventilation was the first choice for ventilated infants. Group B infants showed more severe conditions at birth. During TH, ventilated infants showed optimal mean pCO2 comparable with those breathing spontaneously (40.6 mmHg vs. 42.3 mmHg, respectively, p 0.091), with no significant difference in pCO2 standard deviation between (7.7 mmHg vs. 8.1 mmHg, respectively, p 0.522). Mean pH, pH standard deviation, mean pO2, pO2 standard deviation, and mean respiratory rate also did not differ between groups. MRI patterns of brain injury predictive of abnormal neurodevelopmental outcomes were similar in both groups. Logistic regression analysis demonstrated that only umbilical cord arterial blood pH-affected MRI lesions were associated with poor neurodevelopmental outcomes (OR 1.505; CI 95% 1.069-2.117).

CONCLUSIONS: Infants cooled after HIE should receive individualized respiratory management, not necessarily involving intubation. In those infants requiring mechanical ventilation, a volume-targeted strategy appeared to be effective in maintaining stable blood gas levels. Short-term neurological outcomes appeared comparable in ventilated and non-ventilated infants.}, } @article {pmid38315007, year = {2024}, author = {Hickman, R and Nguyen, J and Lee, TD and Tyson, JR and Azana, R and Tsang, F and Hoang, L and Prystajecky, NA}, title = {Rapid, high-throughput, cost-effective whole-genome sequencing of SARS-CoV-2 using a condensed library preparation of the Illumina DNA Prep kit.}, journal = {Journal of clinical microbiology}, volume = {62}, number = {3}, pages = {e0010322}, pmid = {38315007}, issn = {1098-660X}, mesh = {Humans ; *SARS-CoV-2 ; *COVID-19 ; Cost-Benefit Analysis ; Pandemics ; Gene Library ; DNA ; High-Throughput Nucleotide Sequencing/methods ; }, abstract = {UNLABELLED: The ongoing COVID-19 pandemic necessitates cost-effective, high-throughput, and timely whole-genome sequencing (WGS) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viruses for outbreak investigations, identifying variants of concern (VoC), characterizing vaccine breakthrough infections, and public health surveillance. In addition, the enormous demand for WGS on supply chains and the resulting shortages of laboratory supplies necessitated the use of low-reagent and low-consumable methods. Here, we report an optimized library preparation method (the BCCDC cutdown method) that can be used in a high-throughput scenario, where one technologist can perform 576 library preparations (6 plates of 96 samples) over the course of one 8-hour shift. The same protocol can also be used in a rapid turnaround time scenario, from primary samples (up to 96 samples) to loading on a sequencer in an 8-hour shift. This new method uses Freed et al.'s 1,200 bp primer sets (Biol Methods Protoc 5:bpaa014, 2020, https://doi.org/10.1093/biomethods/bpaa014) and a modified and condensed Illumina DNA Prep workflow (Illumina, CA, USA). Compared to the original protocol, the application of this new method using hundreds of clinical specimens demonstrated equivalent results to the full-length DNA Prep workflow at 45% of the cost, 15% of consumables required (such as pipet tips), 25% of manual hands-on time, and 15% of on-instrument time if performing on a liquid handler, with no compromise in sequence quality. Results demonstrate that this new method is a rapid, simple, cost-effective, and high-quality SARS-CoV-2 WGS protocol.

IMPORTANCE: Sequencing has played an invaluable role in the response to the COVID-19 pandemic. Ongoing work in this area, however, demands optimization of laboratory workflow to increase sequencing capacity, improve turnaround time, and reduce cost without compromising sequence quality. This report describes an optimized DNA library preparation method for improved whole-genome sequencing of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pathogen. The workflow advantages summarized here include significant time, cost, and consumable savings, which suggest that this new method is an efficient, scalable, and pragmatic alternative for SARS-CoV-2 whole-genome sequencing.}, } @article {pmid38311450, year = {2024}, author = {Holleman, GA and Dhami, MK and Hooge, ITC and Hessels, RS}, title = {Representative design: A realistic alternative to (systematic) integrative design.}, journal = {The Behavioral and brain sciences}, volume = {47}, number = {}, pages = {e48}, doi = {10.1017/S0140525X23002200}, pmid = {38311450}, issn = {1469-1825}, abstract = {We disagree with Almaatouq et al. that no realistic alternative exists to the "one-at-a-time" paradigm. Seventy years ago, Egon Brunswik introduced representative design, which offers a clear path to commensurability and generality. Almaatouq et al.'s integrative design cannot guarantee the external validity and generalizability of results which is sorely needed, while representative design tackles the problem head on.}, } @article {pmid38311436, year = {2024}, author = {Hoffman, M and Quillien, T and Burum, B}, title = {The social sciences needs more than integrative experimental designs: We need better theories.}, journal = {The Behavioral and brain sciences}, volume = {47}, number = {}, pages = {e47}, doi = {10.1017/S0140525X23002297}, pmid = {38311436}, issn = {1469-1825}, mesh = {Humans ; *Social Sciences ; *Research Design ; }, abstract = {Almaatouq et al.'s prescription for more integrative experimental designs is welcome but does not address an equally important problem: Lack of adequate theories. We highlight two features theories ought to satisfy: "Well-specified" and "grounded." We discuss the importance of these features, some positive exemplars, and the complementarity between the target article's prescriptions and improved theorizing.}, } @article {pmid38304502, year = {2023}, author = {Pillai, JP and Dodia, V and Monpara, P and Shah, K and Odedra, S}, title = {Assessment of the mineralisation stages of third molars and validation of Mincer et al.'s age estimation method: A retrospective, cross-sectional study in Western India population.}, journal = {Journal of oral and maxillofacial pathology : JOMFP}, volume = {27}, number = {4}, pages = {748-753}, pmid = {38304502}, issn = {0973-029X}, abstract = {CONTEXT: Age estimation is one of the prime requisites in forensic human identification cases and the criminal justice system. There are several age estimation methods using dental parameters. A method proposed by Mincer et al. which uses the mineralization stages of third molars based on Demirjian's developmental stages is less tested in the Indian population.

AIM: The present study aimed to assess the developmental status of the third molars and to apply and validate Mincer et al.'s method on the Western India population.

METHODS AND MATERIAL: A total of 306 orthopantomograms (OPGs) from 128 males and 178 females with a mean age of 16.89 years ± 3.68 were analysed. Demirjian's A-H staging was applied to record the developmental stages of 1100 third molars. Mincer et al.'s mean age of attainment was applied based on the American Whites (Caucasian) population for males and females separately using stages of #18 and #38.

RESULTS: There was a slight overestimation of the chronological age (CA) in both #18 and #38. The females showed more accurate estimated age (EA) than males.

CONCLUSIONS: Mincer et al.'s method is a convenient age estimation method using the third molar's developmental stage. The mean age of attainment mentioned in the original Mincer et al.'s study can be used in the Western Indian population, with a residual value ranging from 0.21 to 0.25 years.}, } @article {pmid38294530, year = {2024}, author = {O'Shea, H and Bek, J}, title = {The complex interplay between perception, cognition, and action: a commentary on Bach et al. 2022.}, journal = {Psychological research}, volume = {88}, number = {6}, pages = {1814-1816}, pmid = {38294530}, issn = {1430-2772}, mesh = {Humans ; *Imagination/physiology ; *Cognition/physiology ; Motor Activity/physiology ; Perception/physiology ; Psychomotor Performance/physiology ; }, abstract = {Bach (Psychological Research 2022, https://doi.org/10.1007/s00426-022-01773-w) offer a re-conceptualisation of motor imagery, influenced by older ideas of ideomotor action and formulated in terms of action effects rather than motor output. We share the view of an essential role of action effect in action planning and motor imagery processes, but we challenge the claim that motor imagery is non-motoric in nature. In the present article, we critically review some of Bach et al.'s proposed ideas and pose questions of whether effect and motor processes are functionally separable, and if not, what mechanisms underlie motor imagery and what terminology best captures its function.}, } @article {pmid38291679, year = {2024}, author = {Tasdemir, V and Sirin, NG and Cakar, A and Culha, A and Soysal, A and Elmali, AD and Gunduz, A and Arslan, B and Yalcin, D and Atakli, D and Orhan, EK and Sanli, E and Tuzun, E and Gozke, E and Gursoy, E and Savrun, FK and Uslu, FI and Aysal, F and Durmus, H and Bulbul, H and Ertas, FI and Uluc, K and Tutkavul, K and Baysal, L and Baslo, MB and Kiziltan, M and Mercan, M and Pazarci, N and Uzun, N and Akan, O and Cokar, O and Koytak, PK and Sürmeli, R and Gunaydin, S and Ayas, S and Baslo, SA and Yayla, V and Yilmaz, V and Parman, Y and Matur, Z and Acar, ZU and Oge, AE}, title = {Electrodiagnostic methods to verify Guillain-Barré syndrome subtypes in Istanbul: A prospective multicenter study.}, journal = {Journal of the peripheral nervous system : JPNS}, volume = {29}, number = {1}, pages = {72-81}, doi = {10.1111/jns.12612}, pmid = {38291679}, issn = {1529-8027}, support = {TSA-2020-36889//Scientific Research Projects Coordination Unit of Istanbul University/ ; }, mesh = {Humans ; *Guillain-Barre Syndrome ; Prospective Studies ; Neural Conduction/physiology ; Electrodiagnosis/methods ; Gangliosides ; Antibodies ; }, abstract = {BACKGROUND AND AIMS: This study aimed to identify the clinical characteristics and electrodiagnostic subtypes of Guillain-Barré syndrome (GBS) in Istanbul.

METHODS: Patients with GBS were prospectively recruited between April 2019 and March 2022 and two electrodiagnostic examinations were performed on each patient. The criteria of Ho et al., Hadden et al., Rajabally et al., and Uncini et al. were compared for the differentiation of demyelinating and axonal subtypes, and their relations with anti-ganglioside antibodies were analyzed.

RESULTS: One hundred seventy-seven patients were included, 69 before the coronavirus disease 2019 pandemic (April 2019-February 2020) and 108 during the pandemic (March 2020-March 2022), without substantial changes in monthly frequencies. As compared with the criteria of Uncini et al., demyelinating GBS subtype diagnosis was more frequent according to the Ho et al. and Hadden et al. criteria (95/162, 58.6% vs. 110/174, 63.2% and 121/174, 69.5%, respectively), and less frequent according to Rajabally et al.'s criteria (76/174, 43.7%). Fourteen patients' diagnoses made using Rajabally et al.'s criteria were shifted to the other subtype with the second electrodiagnostic examination. Of the 106 analyzed patients, 22 had immunoglobulin G anti-ganglioside antibodies (14 with the axonal subtype). They had less frequent sensory symptoms (54.5% vs. 83.1%, p = 0.009), a more frequent history of previous gastroenteritis (54.5% vs. 22.9%, p = 0.007), and a more severe disease as compared with those without antibodies.

INTERPRETATION: Serial electrodiagnostic examinations are more helpful for accurate subtype diagnosis of GBS because of the dynamic pathophysiology of the disease. We observed no significant increase in GBS frequency during the pandemic in this metropolis.}, } @article {pmid38287478, year = {2024}, author = {Kelly, JP}, title = {Expanding the Health Narrative Frame.}, journal = {Health communication}, volume = {39}, number = {13}, pages = {3502-3506}, doi = {10.1080/10410236.2024.2309813}, pmid = {38287478}, issn = {1532-7027}, mesh = {Humans ; *Narration ; *Health Communication/methods ; }, abstract = {How might we expand the frame of health narratives so as to avoid genre calcification and more effectively harness these stories' transformative potential? This essay builds on the continued success of the "Defining Moments" forum while responding to Harter et al.'s 2020 call for "new stories shaped and shared in novel ways." Drawing on interdisciplinary research and theorizing, I suggest three narrative strategies for storytelling based on, respectively, the extended duration of a health context, the agentic power of nonhuman kinds, and the implicit collectivity of polyphonic narratives. Brief examples precede my discussion of each strategy. I invite others to join me in shaping innovative narratives that further challenge tacit assumptions of embodied health.}, } @article {pmid38284619, year = {2025}, author = {Shuman, E and van Zomeren, M and Saguy, T and Knowles, E and Halperin, E}, title = {Defend, Deny, Distance, and Dismantle: A New Measure of Advantaged Identity Management.}, journal = {Personality & social psychology bulletin}, volume = {51}, number = {8}, pages = {1490-1518}, doi = {10.1177/01461672231216769}, pmid = {38284619}, issn = {1552-7433}, mesh = {Humans ; *Social Identification ; Male ; Female ; Adult ; Young Adult ; Israel ; *Interpersonal Relations ; United States ; *Group Processes ; *Psychological Distance ; Adolescent ; Middle Aged ; }, abstract = {The experience of privilege can trigger psychological conflict among advantaged group members. Nonetheless, little work has explored strategies that advantaged group members use to manage their identities as privileged actors. Building on Knowles et al.'s framework and theories of intergroup relations, we address the conceptualization and measurement of advantaged group identity-management strategies. We aim to refine theorizing and validate a measure of these strategies across three contexts (U.S.'s White-Black relations, Israel's Jewish-Arab/Palestinian relations, and U.S.'s gender relations). This process yielded two novel conceptual and empirical contributions. First, we add a strategy-defend-in which advantaged-group members overtly justify inequality. Second, we discover that distancing has two facets (distancing from inequality and from identity). Across six studies, we find support for our proposed factor structure, measurement invariance, and construct validity. We discuss how advantaged groups contend with privilege and offer a tool for studying these strategies across domains and contexts.}, } @article {pmid38279141, year = {2024}, author = {Murphy, JK and Chau, LW and Nguyen, VC and Minas, H and Anh, DV and O'Neil, J}, title = {An integrated knowledge translation (iKT) approach to advancing community-based depression care in Vietnam: lessons from an ongoing research-policy collaboration.}, journal = {BMC health services research}, volume = {24}, number = {1}, pages = {142}, pmid = {38279141}, issn = {1472-6963}, mesh = {Humans ; Vietnam ; *Translational Science, Biomedical ; *Depression ; Pandemics ; Health Policy ; }, abstract = {BACKGROUND: Evidence-based mental health policies are key to supporting the expansion of community-based mental health care and are increasingly being developed in low and middle-income countries (LMICs). Despite this, research on the process of mental health policy development in LMICs is limited. Engagement between researchers and policy makers via an integrated Knowledge Translation (iKT) approach can help to facilitate the process of evidence-based policy making. This paper provides a descriptive case study of a decade-long policy and research collaboration between partners in Vietnam, Canada and Australia to advance mental health policy for community-based depression care in Vietnam.

METHODS: This descriptive case study draws on qualitative data including team meeting minutes, a focus group discussion with research team leaders, and key informant interviews with two Vietnamese policy makers. Our analysis draws on Murphy et al.'s (2021) findings and recommendations related to stakeholder engagement in global mental health research.

RESULTS: Consistent with Murphy et al.'s findings, facilitating factors across three thematic categories were identified. Related to 'the importance of understanding context', engagement between researchers and policy partners from the formative research stage provided a foundation for engagement that aligned with local priorities. The COVID-19 pandemic acted as a catalyst to further advance the prioritization of mental heath by the Government of Vietnam. 'The nature of engagement' is also important, with findings demonstrating that long-term policy engagement was facilitated by continuous funding mechanisms that have enabled trust-building and allowed the research team to respond to local priorities over time. 'Communication and dissemination' are also crucial, with the research team supporting mental health awareness-raising among policy makers and the community, including via capacity building initiatives.

CONCLUSIONS: This case study identifies factors influencing policy engagement for mental health system strengthening in an LMIC setting. Sustained engagement with policy leaders helps to ensure alignment with local priorities, thus facilitating uptake and scale-up. Funding agencies can play a crucial role in supporting mental health system development through longer term funding mechanisms. Increased research related to the policy engagement process in global mental health will further support policy development and improvement in mental health care in LMICs.}, } @article {pmid38271664, year = {2024}, author = {Pineda, R and Kellner, P and Gruskin, BA and Smith, J}, title = {Organizational Barriers to and Facilitators of the Successful Implementation and Sustainability of the Supporting and Enhancing NICU Sensory Experiences (SENSE) Program.}, journal = {The American journal of occupational therapy : official publication of the American Occupational Therapy Association}, volume = {78}, number = {1}, pages = {}, doi = {10.5014/ajot.2024.050450}, pmid = {38271664}, issn = {0272-9490}, mesh = {Infant, Newborn ; Humans ; *Intensive Care Units, Neonatal ; *Infant, Premature ; Health Personnel ; Language ; Allied Health Personnel ; }, abstract = {IMPORTANCE: The Supporting and Enhancing NICU Sensory Experiences (SENSE) program is an evidence-based intervention that promotes daily, positive sensory exposures for infants in the neonatal intensive care unit (NICU). Understanding program implementation across sites may aid in optimizing strategies for uptake of the program and subsequently improve outcomes for infants and families.

OBJECTIVE: To investigate health care professionals' perceptions of implementing the SENSE program.

DESIGN: The SENSE Program Implementation Survey was developed using Proctor et al.'s model and the BARRIERS scale to probe organizational practices across sites worldwide.

SETTING: Survey distributed to 211 hospitals with a SENSE program license obtained before March 2020.

PARTICIPANTS: One hundred fourteen NICU personnel (response rate = 54%).

OUTCOMES AND MEASURES: The survey sought to understand barriers and facilitators, adaptations during implementation, and associated costs.

RESULTS: Of the 53% (n = 57 of 107) of respondents who had implemented the SENSE program, many (n = 14; 31%) experienced quick timing (<1 mo) to use, including spread to nearly all infants in their NICU within 6 mo (n = 18; 35%). Most reported the program was used to educate families ≤3 days of birth (n = 20/59; 34%). Most of the sensory interventions in the program were performed by parents (n = 38; 67%) and therapists (n = 44; 77%). Barriers and facilitators at the organizational and individual levels were identified. No additional staff were hired to implement the program.

CONCLUSIONS AND RELEVANCE: Given perceived successes and challenges, strategic enhancement of implementation can inform future administrations of the SENSE program. Plain-Language Summary: This study provides occupational therapists who are interested in implementing the SENSE program (Supporting and Enhancing NICU Sensory Experiences) with an understanding of common barriers, facilitators, costs, and adaptations, which can be used to advocate for program implementation in NICUs to improve outcomes for preterm infants worldwide.}, } @article {pmid38267281, year = {2024}, author = {Lambert, E and Chartier-Kastler, E and Vaessen, C and Beaugerie, A and Cotte, J and Rouprêt, M and Mozer, P and Parra, J and Seisen, T and Lenfant, L}, title = {Reply to Carmen Gravina, Matteo Romagnoli, Antonio Nacchia, et al.'s Letter to the Editor re: Edward Lambert, Emmanuel Chartier-Kastler, Christophe Vaessen, et al. Robot-assisted Periprostatic Artificial Urinary Sphincter Implantation in Men with Neurogenic Stress Urinary Incontinence: Description of the Surgical Technique and Comparison of Long-term Functional Outcomes with the Open Approach. Eur Urol. 2024;85:139-145.}, journal = {European urology}, volume = {85}, number = {5}, pages = {e140-e141}, doi = {10.1016/j.eururo.2023.12.016}, pmid = {38267281}, issn = {1873-7560}, mesh = {Male ; Humans ; *Urinary Incontinence, Stress/surgery ; *Robotics/methods ; *Urinary Sphincter, Artificial ; Prosthesis Implantation/methods ; *Laparoscopy/methods ; }, } @article {pmid38243425, year = {2023}, author = {Qi, Y and Wang, LP and Guo, Z and Chen, S}, title = {Consistent lifting relations for the initialization of total-energy double-distribution-function kinetic models.}, journal = {Physical review. E}, volume = {108}, number = {6-2}, pages = {065301}, doi = {10.1103/PhysRevE.108.065301}, pmid = {38243425}, issn = {2470-0053}, abstract = {A lifting relation connecting the distribution function explicitly with the hydrodynamic variables is necessary for the Boltzmann equation-based mesoscopic approaches in order to correctly initialize a nonuniform hydrodynamic flow. We derive two lifting relations for Guo et al.'s total-energy double-distribution-function (DDF) kinetic model [Z. L. Guo et al., Phys. Rev. E 75, 036704 (2007)1539-375510.1103/PhysRevE.75.036704], one from the Hermite expansion of the conserved and nonconserved moments, and the second from the O(τ) Chapman-Enskog (CE) approximation of the Maxwellian exponential equilibrium. While both forms are consistent to the compressible Navier-Stokes-Fourier system theoretically, we stress that the latter may introduce numerical oscillations under the recently optimized discrete velocity models [Y. M. Qi et al., Phys. Fluids 34, 116101 (2022)10.1063/5.0120490], namely a 27 discrete velocity model of the seventh-order Gauss-Hermite quadrature (GHQ) accuracy (D3V27A7) for the velocity field combined with a 13 discrete velocity model of the fifth-order GHQ accuracy (D3V13A5) for the total energy. It is shown that the Hermite-expansion-based lifting relation can be alternatively derived from the latter approach using the truncated Hermite-polynomial equilibrium. Additionally, a relationship between the order of CE expansions and the truncated order of Hermite equilibria is developed to determine the minimal order of a Hermite equilibria required to recover any multiple-timescale macroscopic system. Next, three-dimensional compressible Taylor-Green vortex flows with different initial conditions and Ma numbers are simulated to demonstrate the effectiveness and potential issues of these lifting relations. The Hermite-expansion-based lifting relation works well in all cases, while the Chapman-Enskog-expansion-based lifting relation may produce numerical oscillations and a theoretical model is developed to predict such oscillations. Furthermore, the corresponding lifting relations for Qi et al.'s total energy DDF model [Y. M. Qi et al., Phys. Fluids 34, 116101 (2022)10.1063/5.0120490] are derived, and additional simulations are performed to illustrate the generality of our approach.}, } @article {pmid38237267, year = {2024}, author = {Wisbey, K and Lane, R and Neil, J and Advocat, J and Alexander, K and Crabtree, BF and Miller, WL and Russell, G}, title = {Leading primary care under the weight of COVID-19: how leadership was enacted in six australian general practices during 2020.}, journal = {Australian journal of primary health}, volume = {}, number = {}, pages = {}, doi = {10.1071/PY23045}, pmid = {38237267}, issn = {1836-7399}, abstract = {BACKGROUND: The COVID-19 pandemic challenged health care delivery globally, providing unique challenges to primary care. Australia's primary healthcare system (primarily general practices) was integral to the response. COVID-19 tested the ability of primary health care to respond to the greater urgency and magnitude than previous pandemics. Early reflections highlighted the critical role of leaders in helping organisations negotiate the pandemic's consequences. This study explores how general practice leadership was enacted during 2020, highlighting how leadership attributes were implemented to support practice teams.

METHODOLOGY: We performed secondary analysis on data from a participatory prospective qualitative case study involving six general practices in Melbourne, Victoria, between April 2020 and February 2021. The initial coding template based on Miller et al.'s relationship-centred model informed a reflexive thematic approach to data re-analysis, focused on leadership. Our interpretation was informed by Crabtree et al.'s leadership model.

RESULTS: All practices realigned clinical and organisational routines in the early months of the pandemic - hierarchical leadership styles often allowing rapid early responses. Yet power imbalances and exclusive communication channels at times left practice members feeling isolated. Positive team morale and interdisciplinary teamwork influenced practices' ability to foster emergent leaders. However, emergence of leaders generally represented an inherent 'need' for authoritative figures in the crisis, rather than deliberate fostering of leadership.

CONCLUSION: This study demonstrates the importance of collaborative leadership during crises while highlighting areas for better preparedness. Promoting interdisciplinary communication and implementing formal leadership training in crisis management in the general practice setting is crucial for future pandemics.}, } @article {pmid38237129, year = {2024}, author = {Shehan, JN and Tollefson, TT}, title = {Commentary on Benjamin et al.'s "Assessing the Prevalence of Craniomaxillofacial Injuries Among Helmeted and Unhelmeted Electric Scooter Users": A Call to Action for Logical Protection.}, journal = {Facial plastic surgery & aesthetic medicine}, volume = {26}, number = {4}, pages = {505-506}, doi = {10.1089/fpsam.2023.0293}, pmid = {38237129}, issn = {2689-3622}, mesh = {Humans ; *Head Protective Devices/statistics & numerical data ; Craniocerebral Trauma/prevention & control/epidemiology ; Prevalence ; Maxillofacial Injuries/epidemiology ; Motorcycles ; }, } @article {pmid38229413, year = {2024}, author = {Allwood, MA}, title = {Moving forward with a culturally inclusive PTSD Criterion A: Commentary on Marx et al. (2023).}, journal = {Journal of traumatic stress}, volume = {37}, number = {1}, pages = {16-18}, doi = {10.1002/jts.23016}, pmid = {38229413}, issn = {1573-6598}, mesh = {Humans ; *Stress Disorders, Post-Traumatic/psychology ; *Depressive Disorder, Major/psychology ; Life Change Events ; Mental Health ; }, abstract = {In response to Marx et al.'s (2023) article, "The PTSD Criterion A debate: A brief history, current status, and recommendations for moving forward," this commentary offers agreement with the recommendation to conduct population-based studies to inform future Criterion A changes. However, to fully address the debate as to whether Criterion A should be expanded, limited, eliminated, or remain unchanged, it is critical that future population-based research focus on cultural inclusivity and the addition of potentially traumatic experiences that are collective and/or cumulative versus individual and discrete. To further understand the etiology of mental health distress and disorder and the role of adverse life experiences, it is also recommended that adverse event specifiers be added to disorders not currently considered to be event-related. The ability to identify the potential long-term effects of adverse life experiences in relation to disorders other than posttraumatic stress disorder (e.g., major depressive disorder) could help validate experiences, reduce stigma, and further advance research on etiology and interventions.}, } @article {pmid38229074, year = {2024}, author = {Draper, B and Yee, WL and Bowring, A and Naing, W and Kyi, KP and Htay, H and Howell, J and Hellard, M and Pedrana, A}, title = {Patients' experience of accessing hepatitis C treatment through the Myanmar national hepatitis C treatment program: a qualitative evaluation.}, journal = {BMC health services research}, volume = {24}, number = {1}, pages = {80}, pmid = {38229074}, issn = {1472-6963}, mesh = {Humans ; *Health Services Accessibility ; Myanmar ; Health Services ; Patients ; *Hepatitis C/drug therapy/epidemiology ; Qualitative Research ; }, abstract = {BACKGROUND: Globally, 56.8 million people are living with hepatitis C and over three-quarters of those reside in low and middle-income countries (LMICs). Barriers and enablers to hepatitis C care among people who inject drugs in high-income countries are well documented. However, there is scant literature describing the patient experience in LMICs. Understanding the barriers and enablers to care from the patient perspective is important to inform service refinements to improve accessibility and acceptability of hepatitis C care.

METHODS: We conducted a qualitative evaluation of the patient experience of accessing the national hepatitis C program at eight hospital sites in Myanmar. Semi-structured interviews were conducted with four to five participants per site. Interview data were analysed thematically, with deductive codes from Levesque et al.'s (2013) Framework on patient-centred access to healthcare.

RESULTS: Across the eight sites, 38 participants who had completed treatment were interviewed. Barriers to accessing care were mostly related to attending for care and included travel time and costs, multiple appointments, and wait times. Some participants described how they did not receive adequate information on hepatitis C, particularly its transmission routes, and on the level of cirrhosis of their liver and what they were required to do after treatment (i.e. reduce alcohol consumption, liver cirrhosis monitoring). Many participants commented that they had few or no opportunities to ask questions. Provision of treatment at no cost was essential to accessibility, and gratitude for free treatment led to high acceptability of care, even when accessing care was inconvenient.

CONCLUSIONS: These findings highlight the importance of streamlining and decentralising health services, adequate human resourcing and training, and affordable treatment in maximising the accessibility and acceptability of hepatitis C care in LMICs. Findings from this work will inform future service delivery refinements for national program and other decentralised programs to improve accessibility and acceptability of hepatitis C care in Myanmar.}, } @article {pmid38227460, year = {2024}, author = {Choe, R and Lardier, DT and Hess, JM and Blackwell, MA and Amer, S and Ndayisenga, M and Deewa, S and Isakson, B and Goodkind, JR}, title = {Measuring culturally and contextually specific distress among Afghan, Iraqi, and Great Lakes African refugees.}, journal = {The American journal of orthopsychiatry}, volume = {94}, number = {3}, pages = {246-261}, pmid = {38227460}, issn = {1939-0025}, support = {R01 MD007712/MD/NIMHD NIH HHS/United States ; R01 MH127733/MH/NIMH NIH HHS/United States ; }, mesh = {Humans ; *Refugees/psychology ; Female ; Male ; Adult ; Iraq/ethnology ; Afghanistan/ethnology ; Psychological Distress ; Reproducibility of Results ; Young Adult ; Great Lakes Region ; United States ; Stress, Psychological/psychology/ethnology ; Adolescent ; Middle Aged ; Qualitative Research ; }, abstract = {Culturally and contextually valid measurement of psychological distress is critical, given the increasing numbers of forcibly displaced people and transnational migration. This study replicates an inductive process that elicited culturally specific expressions, understandings, and idioms of distress among Afghans to develop culturally specific measures of distress for Great Lakes Africans and Iraqis and expands this methodology to include a focus on the contexts of refugees resettled in the United States. To create the measures, we adapted Miller et al.'s (2006) model for the Afghan Symptom Checklist (ASCL) and conducted 18 semistructured qualitative interviews that attended to refugees' multiple settings; the impact of potentially traumatic events initially and postresettlement; and the experiences and impact of resettlement stressors. We tested the newly developed measures and existing ASCL with 280 recently resettled refugees (< 3 years) from Afghanistan, the Great Lakes region of Africa, and Iraq to assess factor structure, reliability, and construct validity. We successfully replicated and adapted a process for creating culturally specific measures of distress to create reliable and valid scales that consider culturally and contextually specific distress among several groups of forcibly displaced people. Our results highlight the salience of individuals' social contexts and how they are manifested as idioms of distress, bringing together two key areas of research: the social construction of mental health and social determinants of mental health. These findings have implications for improving measurement of psychological distress and for developing multilevel interventions that are culturally resonant and address factors beyond the individual level. (PsycInfo Database Record (c) 2024 APA, all rights reserved).}, } @article {pmid38218112, year = {2024}, author = {de Albuquerque, LCP and Torres, CM and Batista, CEA and Cunha, DRMF and Bizzi, JWJ and Bianchin, MM}, title = {Measuring quality and safety of epilepsy monitoring units in Brazil: Adoption of quality indicators.}, journal = {Seizure}, volume = {115}, number = {}, pages = {68-74}, doi = {10.1016/j.seizure.2023.12.021}, pmid = {38218112}, issn = {1532-2688}, mesh = {Humans ; Brazil ; *Quality Indicators, Health Care ; Video Recording/methods ; Seizures/diagnosis/etiology ; *Epilepsy/diagnosis/etiology ; Monitoring, Physiologic/methods ; Electroencephalography/methods ; }, abstract = {PURPOSE: Drug-resistant epilepsy affects a substantial proportion (30-40 %) of patients with epilepsy, often necessitating video-electroencephalography (video-EEG) monitoring. In 2016, Sauro et al. introduced a set of measures aimed at improving the quality and safety indicators reported in video-EEG evaluations. This study aims to report our experience with the implementation of these measures.

METHODS: We analyzed video-EEG data regarding quality and safty from a period spanning January 2016 to January 2018, involving a total of 101 patients monitored in our video-EEG unit.

RESULTS: Among the patients included in the study, a definitive diagnosis was attainable for 92.1 %, with 36.6 % experiencing a change in diagnosis and 65.3 % undergoing a change in treatment as a result of the video-EEG evaluation. Additionally, the referral question was fully addressed in 60.4 % of admissions, and video-EEG was considered to be very useful or extremely useful in 66.4 % of cases. Adverse events were observed in 26.7 % of patients, with the most common being the progression of focal seizures to bilateral tonic-clonic seizures (11.9 %) and the occurrence of seizure clusters (5.9 %).

CONCLUSION: Our findings support the implementation of Sauro et al.'s set of measures, as they provide valuable criteria for improving the reporting of video-EEG quality and safety indicators. However, challenges may arise due to variations in terminology across studies and the lack of standardized criteria for defining essential questions in video-EEG evaluations. Further research utilizing these measures is necessary to enhance their effectiveness and encourage consistent reporting of results from epilepsy monitoring units.}, } @article {pmid38215538, year = {2024}, author = {Garizoain, G and Parra, RC and Aranda, CM and Luna, LH}, title = {Three decades after the publication of the Lamendin method for adult age-at-death estimation: Methodological evolution of the procedure and interpretations.}, journal = {Forensic science international}, volume = {355}, number = {}, pages = {111917}, doi = {10.1016/j.forsciint.2023.111917}, pmid = {38215538}, issn = {1872-6283}, mesh = {Adult ; Humans ; Middle Aged ; Aged ; *Tooth Root ; Reproducibility of Results ; Bayes Theorem ; *Age Determination by Teeth/methods ; }, abstract = {More than three decades have passed since the publication of Lamendin et al.'s proposal in 1992. Over this time, numerous investigations have been conducted to assess the applicability of the technique in different populations with acceptable results in terms of estimation errors. The proposal by Lamendin and colleagues remains relevant today, and has made a significant contribution to adult age-at-death estimation due to its simplicity, repeatability, replicability, and high performance. Indeed, significant progress towards systematizing and strengthening the procedure has been reported in the published literature. One noteworthy advancement is the development of an international database that supports the use of Bayesian statistics for age-at-death estimation. This resource plays a crucial role in standardizing the methodology and improving the reliability for obtaining more reliable results on a global scale. The aim of this study is to investigate the historical evolution of the technique, to assess the accuracy of the results obtained by different analytic procedures, and to explore its impact in forensic applications through a systematic analysis of the specialized literature on this field. The current state of research indicates that this type of methodological research is an ongoing process, far from being completed. Many questions and challenges that require further attention to address effectively these issues remain unanswered, such as the development of non-linear regressions and probabilistic approaches, the deepening of procedures that improve global approximations, and the intensification of research focused on achieving more accurate estimations among individuals over 70 years-old. However, studies generally agree that the Lamendin technique works well for individuals between the ages of 30-60 years. It is still in force today, although the method has been significantly perfected. Despite the degree of research development in this area, further efforts are needed to improve the understanding and performance of these kinds of procedures. This will ultimately lead to an improvement in the accuracy and reliability of forensic investigation results worldwide.}, } @article {pmid38204780, year = {2024}, author = {Han, J and Zhang, M and Liu, J and Song, Y and Yamada, Y}, title = {The Medusa effect: a registered replication report of Will, Merritt, Jenkins and Kingstone (2021).}, journal = {Royal Society open science}, volume = {11}, number = {1}, pages = {231802}, pmid = {38204780}, issn = {2054-5703}, abstract = {Will et al.'s (2021 Proc. Natl Acad. Sci. USA 118, e2106640118 (doi:10.1073/pnas.2106640118)) found the Medusa effect, which refers to the tendency that people evaluate a 'person in picture' more mindful than a 'person in picture of a picture'. The present study tried to directly replicate the Experiments 2 and 5 of Will et al.'s (2021), to examine the reliability, validity and generalization of the Medusa effect, as well as its effect on prosocial behaviour. We used the same stimuli and methodology as the original research, but recruited participants in Japan with a larger sample size (N = 1387 in total) as a registered report. In our two replication experiments, we again found that pictures with lower levels of abstraction (L1) were perceived to convey more mind and lead to higher levels of prosocial behaviour, successfully replicating the original findings. The results of the present study suggested the high reproducibility and generalizability of the Medusa effect. Pre-registered Stage 1 protocol: https://osf.io/xj46z (date of in-principle acceptance: 9 February 2023).}, } @article {pmid38183969, year = {2023}, author = {AlOtaibi, NN and Aldawood, FA and AlQahtani, SJ}, title = {Accuracy of dental age estimations based on individual teeth and staging system comparisons.}, journal = {The Journal of forensic odonto-stomatology}, volume = {41}, number = {3}, pages = {13-25}, pmid = {38183969}, issn = {2219-6749}, mesh = {Child ; Humans ; *Incisor ; Molar ; Confusion ; *Household Articles ; Metal Workers ; }, abstract = {AIM: To investigate whether a specific tooth or teeth provide the most accurate estimation of chronological age (CA), and determine which of the three staging systems studied represents dental development for an individual tooth.

METHOD: Data were collected from 400 digital panoramic radiographs of healthy Saudi children aged 6.00-15.99 years. Each permanent tooth on the left side was evaluated to determine its developmental stage and dental age using the methods by Moorrees, Fanning, and Hunt (MFH) (1963), as adapted by Smith (1991), Gleiser and Hunt (1955), and Nicodemo et al. (1974). The accuracy (bias) of each tooth type and stage was assessed in relation to the CA, the teeth and the methods were compared, and the accuracy of age estimation using all teeth and the most accurate tooth in each method were compared.

RESULTS: Regarding staging systems, comparatively, Gleiser and Hunt's method had the lowest bias for the lower first molar (-0.50 ± 1.05 years). Nicodemo et al.'s method had a lower bias for all other mandibular teeth compared to the MFH method. For individual teeth using the MFH method, the most and least accurate teeth for the combined sexes were the lower central incisor (-0.59 ± 0.77 years) and the lower first molar (-1.54 ± 0.93 years), respectively. No significant difference was found between the biases when using the lower central incisor alone and when using all teeth for the combined sexes. For individual teeth using Nicodemo et al.'s method, the most and least accurate teeth for combined sexes were the upper central incisor (-0.03 ± 1.01 years) and the lower first molar (-1.08 ± 1.59 years), respectively. A significant difference was found between the biases using the upper central incisor alone and all teeth for the combined sexes, with the upper central incisor exhibiting the lowest bias (P=0.028).

CONCLUSIONS: Comparatively, Nicodemo et al.'s method had the lowest bias for all teeth except for the lower first molar, where Gleiser and Hunt's method had the lowest bias. This, however, should not be confused with precision. MFH's staging system was more representative of dental development for an individual tooth. For combined sexes, the lower central and lateral incisors were the most accurate teeth using the MFH method. The upper central incisor and lower first premolar were the most accurate teeth using Nicodemo et al.'s method. The lower first molar was the least accurate tooth using both methods.}, } @article {pmid38181731, year = {2024}, author = {Alvarado, CX and Makarious, MB and Weller, CA and Vitale, D and Koretsky, MJ and Bandres-Ciga, S and Iwaki, H and Levine, K and Singleton, A and Faghri, F and Nalls, MA and Leonard, HL}, title = {omicSynth: An open multi-omic community resource for identifying druggable targets across neurodegenerative diseases.}, journal = {American journal of human genetics}, volume = {111}, number = {1}, pages = {150-164}, pmid = {38181731}, issn = {1537-6605}, support = {Z01 AG000949/ImNIH/Intramural NIH HHS/United States ; ZIA AG000534/ImNIH/Intramural NIH HHS/United States ; ZIA NS003154/ImNIH/Intramural NIH HHS/United States ; }, mesh = {Humans ; *Alzheimer Disease/drug therapy/genetics ; Community Resources ; Multiomics ; *Neurodegenerative Diseases/drug therapy/genetics ; *Parkinson Disease ; Mendelian Randomization Analysis ; }, abstract = {Treatments for neurodegenerative disorders remain rare, but recent FDA approvals, such as lecanemab and aducanumab for Alzheimer disease (MIM: 607822), highlight the importance of the underlying biological mechanisms in driving discovery and creating disease modifying therapies. The global population is aging, driving an urgent need for therapeutics that stop disease progression and eliminate symptoms. In this study, we create an open framework and resource for evidence-based identification of therapeutic targets for neurodegenerative disease. We use summary-data-based Mendelian randomization to identify genetic targets for drug discovery and repurposing. In parallel, we provide mechanistic insights into disease processes and potential network-level consequences of gene-based therapeutics. We identify 116 Alzheimer disease, 3 amyotrophic lateral sclerosis (MIM: 105400), 5 Lewy body dementia (MIM: 127750), 46 Parkinson disease (MIM: 605909), and 9 progressive supranuclear palsy (MIM: 601104) target genes passing multiple test corrections (pSMR_multi < 2.95 × 10[-6] and pHEIDI > 0.01). We created a therapeutic scheme to classify our identified target genes into strata based on druggability and approved therapeutics, classifying 41 novel targets, 3 known targets, and 115 difficult targets (of these, 69.8% are expressed in the disease-relevant cell type from single-nucleus experiments). Our novel class of genes provides a springboard for new opportunities in drug discovery, development, and repurposing in the pre-competitive space. In addition, looking at drug-gene interaction networks, we identify previous trials that may require further follow-up such as riluzole in Alzheimer disease. We also provide a user-friendly web platform to help users explore potential therapeutic targets for neurodegenerative diseases, decreasing activation energy for the community.}, } @article {pmid38180685, year = {2024}, author = {Anis, S and Khan, MA and Fatima, A and Kanani, F and Aijaz, J and Hussain, A and Sarfaraz, S}, title = {Response to: regarding the significance of anti-COVID-IgA antibody response in COVID-19 breakthrough infection.}, journal = {Immunologic research}, volume = {72}, number = {3}, pages = {366-367}, pmid = {38180685}, issn = {1559-0755}, mesh = {Humans ; *COVID-19/immunology/prevention & control ; *Antibodies, Viral/immunology/blood ; *SARS-CoV-2/immunology ; *COVID-19 Vaccines/immunology ; *Immunoglobulin A/immunology/blood ; Vaccination ; Immunocompromised Host/immunology ; Antibody Formation/immunology ; Breakthrough Infections ; }, abstract = {In response to Chen et al.'s comments on our paper regarding the significance of anti-COVID-IgA antibody response in COVID-19 breakthrough infection in vaccinated patients, we have highlighted the role and the scope of this paper in this correspondence. The role of anti-COVID-19-IgA is already known. The objective of the previous study was to see its role in breakthrough-infected patients. To analyse this effect, we recruited patients with COVID-19 infection after they were fully vaccinated and compared them with the vaccinated group who did not get the infection. Both groups were equally exposed to the virus as all of them were health care workers. We also showed that the anti-COVID-19-NP-IgA was absent in the healthy cohort of our study groups, signifying the absence of natural infection in them during this period. The article also highlights the importance of vaccinating all individuals including those who are immunosuppressed, as it prevents severe COVID-19 infection in these individuals. The physicians should be aware of the fact that immunosuppressed patients are more likely to get COVID-19 breakthrough infection. However, proper vaccination with booster doses prevents severe infection in them.}, } @article {pmid38180246, year = {2024}, author = {Lee, HM and Shih, PC and Wei, JC}, title = {Comment on Shao et al.'s "Risk factors associated with COVID-19 pneumonia in Chinese patients with pre-existing interstitial lung disease during the SARS-CoV-2 pandemic".}, journal = {Journal of medical virology}, volume = {96}, number = {1}, pages = {e29383}, doi = {10.1002/jmv.29383}, pmid = {38180246}, issn = {1096-9071}, mesh = {Humans ; *SARS-CoV-2 ; *COVID-19/epidemiology ; Pandemics ; Risk Factors ; China/epidemiology ; }, } @article {pmid38179006, year = {2023}, author = {Trüeb, RM and Luu, NC and Rezende, HD}, title = {Comment on Topical Dapsone for Folliculitis Decalvans.}, journal = {International journal of trichology}, volume = {15}, number = {3}, pages = {88-90}, pmid = {38179006}, issn = {0974-7753}, abstract = {Folliculitis decalvans (FD) represents a chronic and recurrent pustulofollicular scalp inflammation resulting in scarring alopecia. The presence of a bacterial bioflilm at the interface of the hair shaft may provide an explanation for the chronicity and high relapse rate of FD, even after prolonged systemic antibiotic treatments. We originally read with enthusiasm Melián-Olivera et al.'s retrospective study of patients with FD treated with topical dapsone published in the Journal of the American Academy of Dermatology. However, we experienced an unsuccessful trial of 5% dapsone gel in a patient with FD resulting in worsening of the disease with a pustular flareup and questioned why positive study reports with novel therapeutic options in dermatology often fail in practice. The authors admitted the limitations of their study: small sample size, retrospective, uncontrolled nature of the study, and concomitant use of other treatments. Clinical research ultimately aims at improving the patient outcome. For this purpose, trials must evaluate the outcomes that genuinely reflect the clinical utility of drugs. Therefore, we postulate stricter criteria for treatment trials and statistics in dermatology before publication in peer-reviewed scientific journals to avoid frustrations of physicians and patients alike.}, } @article {pmid38177559, year = {2024}, author = {Gutkin, A and Suero, M and Botella, J and Juola, JF}, title = {Benefits of multinomial processing tree models with discrete and continuous variables in memory research: an alternative modeling proposal to Juola et al. (2019).}, journal = {Memory & cognition}, volume = {52}, number = {4}, pages = {793-825}, pmid = {38177559}, issn = {1532-5946}, mesh = {Humans ; *Recognition, Psychology/physiology ; *Models, Psychological ; *Reaction Time/physiology ; Signal Detection, Psychological/physiology ; Models, Statistical ; Adult ; }, abstract = {Signal detection theory (SDT) and two-high threshold models (2HT) are often used to analyze accuracy data in recognition memory paradigms. However, when reaction times (RTs) and/or confidence levels (CLs) are also measured, they usually are analyzed separately or not at all as dependent variables (DVs). We propose a new approach to include these variables based on multinomial processing tree models for discrete and continuous variables (MPT-DC) with the aim to compare fits of SDT and 2HT models. Using Juola et al.'s (2019, Memory & Cognition, 47[4], 855-876) data we have found that including CLs and RTs reduces the standard errors of parameter estimates and accounts for interactions among accuracy, CLs, and RTs that classical versions of SDT and 2HT models do not. In addition, according to the simulations, there is an increase in the proportion of correct model selections when relevant DV are included. We highlight the methodological and substantive advantages of MPT-DC in the disentanglement of contributing processes in recognition memory.}, } @article {pmid38174362, year = {2024}, author = {Chang, MC}, title = {Regarding Yalçınkaya et al.'s "Ossified/sequestrated lumbar disc: A ricochet in diffuse idiopathic skeletal hyperostosis".}, journal = {Pain practice : the official journal of World Institute of Pain}, volume = {24}, number = {5}, pages = {817}, doi = {10.1111/papr.13344}, pmid = {38174362}, issn = {1533-2500}, mesh = {Humans ; *Hyperostosis, Diffuse Idiopathic Skeletal/complications/diagnostic imaging ; *Lumbar Vertebrae/diagnostic imaging ; Intervertebral Disc/diagnostic imaging ; }, } @article {pmid38165996, year = {2024}, author = {Kusumaningrum, FM and Dewi, FST and Santosa, A and Pangastuti, HS and Yeung, P}, title = {Factors related to quality of life in community-dwelling adults in Sleman Regency, Special Region of Yogyakarta, Indonesia: Results from a cross-sectional study.}, journal = {PloS one}, volume = {19}, number = {1}, pages = {e0296245}, pmid = {38165996}, issn = {1932-6203}, mesh = {Aged ; Adult ; Humans ; *Independent Living/psychology ; *Quality of Life/psychology ; Cross-Sectional Studies ; Activities of Daily Living/psychology ; Indonesia/epidemiology ; Geriatric Assessment/methods ; Chronic Disease ; }, abstract = {BACKGROUND: Quality of life studies in low- and middle-income countries have demonstrated the influence of socioeconomic factors on the quality of life (QoL). However, further studies are required to confirm this association in developing countries with rapidly ageing populations. Using Ferrans et al.'s QoL model, this study aimed to identify the factors associated with the QoL of community-dwelling adults in Indonesia.

METHODS: A cross-sectional study among 546 community-dwelling adults aged 50+ years was conducted in Yogyakarta, Indonesia, in 2018. QoL was measured using the Short Form 12 questionnaire, which consists of a summary of physical and mental health. We performed stepwise logistic regression analyses to determine odds ratios (ORs) with 95% confidence intervals (CIs) and examined the association between the QoL (physical and mental health) and demographic characteristics, socioeconomic status, financial management behaviour, multimorbidity status, nutritional status, cognitive impairment status, depression status, and independence. Statistical significance was set at p<0.05.

RESULTS: Among the respondents, 15% reported poor physical health, and 9.2% reported poor mental health. Good physical health was significantly associated with the absence of chronic disease (OR 2.39; 95% CI: 1.07-5.33), independence in activities of daily living (OR 3.90; 95% CI 1.57-9.67) and instrumental activities of daily living (OR 4.34; 95% CI 2.28-8.26). Absence of depression was significantly associated with good mental health (OR 2.80; 95% CI 1.3-5.96).

CONCLUSION: The QoL of community-dwelling adults in Indonesia is associated with activities of daily living and instrumental activities of daily living, as well as the absence of chronic disease and depression. Efforts should be made to prevent chronic disease and delay functional decline through healthy lifestyles and routine physical and mental health screenings.}, } @article {pmid38159049, year = {2024}, author = {Wang, KP and Yu, CL and Shen, C and Schack, T and Hung, TM}, title = {A longitudinal study of the effect of visuomotor learning on functional brain connectivity.}, journal = {Psychophysiology}, volume = {61}, number = {5}, pages = {e14510}, doi = {10.1111/psyp.14510}, pmid = {38159049}, issn = {1469-8986}, support = {MOST 103-2410-H-003 -113 -MY3//Ministry of Science and Technology, Taiwan/ ; }, mesh = {Humans ; Male ; *Brain ; Brain Mapping/methods ; Electroencephalography ; Learning ; Longitudinal Studies ; *Motor Cortex ; }, abstract = {Neural adaptation in the frontoparietal and motor cortex-sensorimotor circuits is crucial for acquiring visuomotor skills. However, the specific nature of highly dynamic neural connectivity in these circuits during the acquisition of visuomotor skills remains unclear. To achieve a more comprehensive understanding of the relationship between acquisition of visuomotor skills and neural connectivity, we used electroencephalographic coherence to capture highly dynamic nature of neural connectivity. We recruited 60 male novices who were randomly assigned to either the experimental group (EG) or the control group (CG). Participants in EG were asked to engage in repeated putting practice, but CG did not engage in golf practice. In addition, we analyzed the connectivity by using 8-13 Hz imaginary inter-site phase coherence in the frontoparietal networks (Fz-P3 and Fz-P4) and the motor cortex-sensorimotor networks (Cz-C3 and Cz-C4) during a golf putting task. To gain a deeper understanding of the dynamic nature of learning trajectories, we compared data at three time points: baseline (T1), 50% improvement from baseline (T2), and 100% improvement from baseline (T3). The results primarily focused on EG, an inverted U-shaped coherence curve was observed in the connectivity of the left motor cortex-sensorimotor circuit, whereas an increase in the connectivity of the right frontoparietal circuit from T2 to T3 was revealed. These results imply that the dynamics of cortico-cortical communication, particularly involving the left motor cortex-sensorimotor and frontal-left parietal circuits. In addition, our findings partially support Hikosaka et al.'s model and provide additional insight into the specific role of these circuits in visuomotor learning.}, } @article {pmid38158151, year = {2024}, author = {Pesta, D}, title = {Mitochondrial density in skeletal and cardiac muscle.}, journal = {Mitochondrion}, volume = {75}, number = {}, pages = {101838}, doi = {10.1016/j.mito.2023.101838}, pmid = {38158151}, issn = {1872-8278}, mesh = {Humans ; *Mitochondria, Muscle/metabolism ; *Muscle, Skeletal/metabolism ; Muscle Fibers, Skeletal ; Mitochondria ; Myocytes, Cardiac ; Citrate (si)-Synthase/metabolism ; }, abstract = {Kubat et al. provide a review on the role Mitochondrial density in skeletal and cardiac muscle of mitochondrial dysfunction in muscle atrophy. They stress mitochondria's pivotal function, citing a 52 % density in skeletal muscle. However, the reference to Park et al.'s work misinterprets their findings. Park et al. report citrate synthase (CS) activity, indicating mitochondrial density as 222 ± 13 μmol.min[-1].mg[-1] for cardiac muscle and 115 ± 2 μmol.min[-1].mg[-1] for skeletal muscle. Thus, the authors should clarify that skeletal muscle density is approximately 52 % of cardiac muscle, not an absolute 52 %. Mitochondrial volume density assessment, predominantly through TEM, establishes cardiomyocytes at 25-30 % and untrained skeletal muscle at 2-6 %, increasing to 11 % in trained athletes. However, this remains modest compared to myofibrils' 75 %-85 % of muscle fiber volume. Although the utility of CS activity is evident, TEM and other novel approaches such as three-dimensional focused ion beam scanning electron microscopy are likely superior for assessing mitochondrial volume density and morphology.}, } @article {pmid38155249, year = {2023}, author = {Mashayekh-Amiri, S and Asghari Jafarabadi, M and Rashidi, F and Mirghafourvand, M}, title = {Psychometric evaluation and cross-cultural adaptation of the Australian Pelvic Floor Questionnaire (APFQ-IR) in Iranian reproductive age women.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {23015}, pmid = {38155249}, issn = {2045-2322}, mesh = {Humans ; Female ; Iran ; *Pelvic Floor Disorders/diagnosis ; Cross-Cultural Comparison ; Psychometrics ; Cross-Sectional Studies ; Reproducibility of Results ; Pelvic Floor ; Australia ; Quality of Life ; Surveys and Questionnaires ; }, abstract = {Pelvic floor disorders (PFDs), as a silent alert, is one of the pervasive debilitating health concerns among women all over the world, such that in developed countries, one in four women, suffers from PFDs. Validity and reliability of the Australian Pelvic Floor Questionnaire (APFQ) has not been determined in Iran, so to determine APFQ's psychometric characteristics, we decided to conduct this study on women of reproductive age in Tabriz city, Iran. This methodological cross-sectional study was intended to determine the psychometric properties of the Persian version of the APFQ-IR in 5 steps including "translation process, content validity, face validity, construct validity (exploratory and confirmatory factor analyses and examination of ceiling and floor effects) and reliability" on 400 reproductive age women referring to health centers in Tabriz city, Iran, with cluster random sampling method in the period between May 2022 to September 2022. The translation process was done based on two approaches, Dual panel, and Beaton et al.'s five steps. Then, in order to evaluate content validity, face validity, and construct validity, 10 instrument and PFDs experts, 10 women from the target group investigated the instrument's items, and 400 eligible women completed the instrument. Finally, to determine the reliability, two internal consistency methods, (Cronbach's alpha and McDonald's omega) and test-retest method (ICC) were used. In the present study, content validity assessment of APFQ-IR, showed a good level of validity (CVR = 0.96, CVI = 0.94). To assess construct validity, exploratory factor analysis results on 36 items, led to the identification of 4 factors including bladder function, bowel function, prolapse symptom and sexual function, which explained 45.53% of the cumulative variance and indicated the sufficiency of the sample size (Kaiser-Meyer-Olkin = 0.750). Implementing confirmatory factor analysis, (RMSEA = 0.08, SRMR = 0.08, TLI = 0.90, CFI = 0.93, χ[2]/df = 3.52) confirmed the model fit indices. Finally the internal consistency and reliability was high for the entire instrument (Cronbach's alpha = 0.85; McDonald's omega (95% CI) = 0.85 (0.83-0.87) and Intraclass Correlation Coefficient (95% CI) = 0.88 (0.74-0.94)). The Persian version of the APFQ-IR, has a good validity and reliability and has acceptable psychometric properties, thus can be used both for research purposes and for clinical evaluation of pelvic floor disorders symptoms in health centers.}, } @article {pmid38152836, year = {2023}, author = {Spears, D and Zuber, S}, title = {Foundations of utilitarianism under risk and variable population.}, journal = {Social choice and welfare}, volume = {61}, number = {1}, pages = {101-129}, pmid = {38152836}, issn = {0176-1714}, support = {K01 HD098313/HD/NICHD NIH HHS/United States ; P2C HD042849/HD/NICHD NIH HHS/United States ; }, abstract = {Utilitarianism is the most prominent social welfare function in economics. We present three new axiomatic characterizations of utilitarian (that is, additively-separable) social welfare functions in a setting where there is risk over both population size and individuals' welfares. We first show that, given uncontroversial basic axioms, Blackorby et al.'s (1998) Expected Critical-Level Generalized Utilitarianism is equivalent to a new axiom holding that it is better to allocate higher utility-conditional-on-existence to possible people who have a higher probability of existence. The other two characterizations extend and clarify classic axiomatizations of utilitarianism from settings with either social risk or variable-population, considered alone.}, } @article {pmid38151660, year = {2024}, author = {Chen, J and Gale, RP}, title = {Response to Pfirrmann et al.'s comment on How should we interpret conclusions of TKI-stopping studies.}, journal = {Leukemia}, volume = {38}, number = {2}, pages = {463-464}, pmid = {38151660}, issn = {1476-5551}, support = {2021-I2M-1-001//Chinese Academy of Medical Sciences (CAMS)/ ; 2022-I2M-2-003//Chinese Academy of Medical Sciences (CAMS)/ ; 82370212//National Natural Science Foundation of China (National Science Foundation of China)/ ; 84000-51200002//Ministry of Science and Technology of the People's Republic of China (Chinese Ministry of Science and Technology)/ ; }, mesh = {Humans ; *Protein Kinase Inhibitors/pharmacology/therapeutic use ; *Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; }, } @article {pmid38139612, year = {2023}, author = {Ju, S and Park, Y}, title = {Provably Secure Lightweight Mutual Authentication and Key Agreement Scheme for Cloud-Based IoT Environments.}, journal = {Sensors (Basel, Switzerland)}, volume = {23}, number = {24}, pages = {}, pmid = {38139612}, issn = {1424-8220}, support = {2022//Keimyung University/ ; }, abstract = {A paradigm that combines cloud computing and the Internet of Things (IoT) allows for more impressive services to be provided to users while addressing storage and computational resource issues in the IoT environments. This cloud-based IoT environment has been used in various industries, including public services, for quite some time, and has been researched in academia. However, various security issues can arise during the communication between IoT devices and cloud servers, because communication between devices occurs in open channels. Moreover, issues such as theft of a user's IoT device or extraction of key parameters from the user's device in a remote location can arise. Researchers interested in these issues have proposed lightweight mutual authentication key agreement protocols that are safe and suitable for IoT environments. Recently, a lightweight authentication scheme between IoT devices and cloud servers has been presented. However, we found out their scheme had various security vulnerabilities, vulnerable to insider, impersonation, verification table leakage, and privileged insider attacks, and did not provide users with untraceability. To address these flaws, we propose a provably secure lightweight authentication scheme. The proposed scheme uses the user's biometric information and the cloud server's secret key to prevent the exposure of key parameters. Additionally, it ensures low computational costs for providing users with real-time and fast services using only exclusive OR operations and hash functions in the IoT environments. To analyze the safety of the proposed scheme, we use informal security analysis, Burrows-Abadi-Needham (BAN) logic and a Real-or-Random (RoR) model. The analysis results confirm that our scheme is secure against insider attacks, impersonation attacks, stolen verifier attacks, and so on; furthermore, it provides additional security elements. Simultaneously, it has been verified to possess enhanced communication costs, and total bit size has been shortened to 3776 bits, which is improved by almost 6% compared to Wu et al.'s scheme. Therefore, we demonstrate that the proposed scheme is suitable for cloud-based IoT environments.}, } @article {pmid38131859, year = {2023}, author = {Rosales, KP and Wong, EH and Looney, L}, title = {The Psychometric Structure of Executive Functions: A Satisfactory Measurement Model? An Examination Using Meta-Analysis and Network Modeling.}, journal = {Behavioral sciences (Basel, Switzerland)}, volume = {13}, number = {12}, pages = {}, pmid = {38131859}, issn = {2076-328X}, abstract = {A long-standing debate among cognitive scientists has focused on describing the underlying nature of executive functions, which has important implications for both theoretical and applied research. Miyake et al.'s three-factor model has often been considered the gold-standard representation of executive functions and has driven much research in the field. More recently, however, there have been increasing concerns that the three-factor model does not adequately describe a highly complex construct such as executive functions. The current project presents two studies that examine the veracity of Miyake et al.'s model and propose a new approach (i.e., network modeling) for detecting the underlying nature of executive functions. The current results raise questions about the psychometric strength and adequacy of the three-factor model. Further, the studies presented here provide evidence that network modeling provides a better understanding of executive functions as it better captures (relative to latent variable modeling) the complexity of cognitive processes. Theoretical and applied implications are discussed.}, } @article {pmid38111717, year = {2023}, author = {Almroth, H and Karlsson, LO and Carlhäll, CJ and Charitakis, E}, title = {Response to Kataoka et al.'s 'How to assess haemodynamic impact of atrial fibrillation'.}, journal = {European heart journal open}, volume = {3}, number = {6}, pages = {oead126}, pmid = {38111717}, issn = {2752-4191}, } @article {pmid38105389, year = {2024}, author = {Paton, M and Zakeri, B and Rowland, P and Tavares, W and Williams, BW and Schneeweiss, S and Wiljer, D}, title = {Decision making in continuing professional development organisations during a crisis.}, journal = {Medical education}, volume = {58}, number = {6}, pages = {722-729}, doi = {10.1111/medu.15265}, pmid = {38105389}, issn = {1365-2923}, mesh = {*COVID-19 ; Humans ; *Education, Medical, Continuing/organization & administration ; *Qualitative Research ; SARS-CoV-2 ; Decision Making ; Pandemics ; Ontario ; Interviews as Topic ; }, abstract = {INTRODUCTION: Early in COVID-19, continuing professional development (CPD) providers quickly made decisions about program content, design, funding and technology. Although experiences during an earlier pandemic cautioned providers to make disaster plans, CPD was not entirely prepared for this event. We sought to better understand how CPD organisations make decisions about CPD strategy and operations during a crisis.

METHODS: This is a descriptive qualitative research study of decision making in two organisations: CPD at the University of Toronto (UofT) and the US-based Society for Academic Continuing Medical Education (SACME). In March 2021, using purposive and snowball sampling, we invited faculty and staff who held leadership positions to participate in semi-structured interviews. The interview focused on the individual's role and organisation, their decision-making process and reflections on how their units had changed because of COVID-19. Transcripts were reviewed, coded and analysed using thematic analysis. We used Mazmanian et al.'s Ecological Framework as a further conceptual tool.

RESULTS: We conducted eight interviews from UofT and five from SACME. We identified that decision making during the pandemic occurred over four phases of reactions and impact from COVID-19, including shutdown, pivot, transition and the 'new reality'. The decision-making ability of CPD organisations changed throughout the pandemic, ranging from having little or no independent decision-making ability early on to having considerable control over choosing appropriate pathways forward. Decision making was strongly influenced by the creativity, adaptability and flexibility of the CPD community and the need for social connection.

CONCLUSIONS: This adds to literature on the changes CPD organisations faced due to COVID-19, emphasising CPD organisations' adaptability in making decisions. Applying the Ecological Framework further demonstrates the importance of time to decision-making processes and the relational aspect of CPD. To face future crises, CPD will need to embrace creative, flexible and socially connected solutions. Future scholarship could explore an organisation's ability to rapidly adapt to better prepare for future crises.}, } @article {pmid38104421, year = {2024}, author = {Albery, IP and Milia, C and Gunstone, B and Spada, MM and Moss, AC}, title = {Components of identity expression in problem and non-problem gamblers.}, journal = {Addictive behaviors}, volume = {151}, number = {}, pages = {107936}, doi = {10.1016/j.addbeh.2023.107936}, pmid = {38104421}, issn = {1873-6327}, mesh = {Humans ; *Gambling ; *Behavior, Addictive ; Social Identification ; }, abstract = {Few studies have examined whether specific aspects of group identification predict problematic and non-problematic addictive behaviours and none have focused on gambling. Applying Leach et al.'s (2008) hierarchical model of in-group identification, we tested the associations between components of self-investment (satisfaction, solidarity, and centrality) and components of self-definition (individual self-stereotyping, in-group homogeneity) on distinguishing between problem and non-problem gambling (n = 10,157) and on the severity of problematic gambling behaviour (n = 2,568). Results showed that (i) in-group-based identities are important in predicting problematic vs. non-problematic gambling behaviours; (ii) in-group-based identities are important in predicting the severity of problematic gambling; (iii) how self-invested an individual is with their in-group and aspects associated with self-definition processes are both important predictors; (iv) perceptions related to how chronically salient one's group membership is for the self (centrality) are essential features of the self-investment mechanism; and (v) self-stereotypical beliefs about one's essential similarities to the prototypical gambling group member norm are fundamental for the defining oneself as a gambler.}, } @article {pmid38103919, year = {2024}, author = {Kettrey, HH and Thompson, MP and Marx, RA and Davis, AJ}, title = {Kettrey et al.'s Meta-Analysis Is Not About Empowerment Self-Defense Programs: A Response to Hollander et al.}, journal = {The Journal of adolescent health : official publication of the Society for Adolescent Medicine}, volume = {74}, number = {1}, pages = {209-210}, doi = {10.1016/j.jadohealth.2023.10.002}, pmid = {38103919}, issn = {1879-1972}, } @article {pmid38103918, year = {2024}, author = {Hollander, JA and Edwards, KM and McCaughey, M and Cermele, J and Ullman, SE and Senn, CY and Beaujolais, B and Orchowski, LM and Peitzmeier, SM}, title = {Empowerment Self-Defense Prevents Rape: A Response to Kettrey et al.'s Meta-Analysis.}, journal = {The Journal of adolescent health : official publication of the Society for Adolescent Medicine}, volume = {74}, number = {1}, pages = {208-209}, doi = {10.1016/j.jadohealth.2023.08.009}, pmid = {38103918}, issn = {1879-1972}, mesh = {Humans ; *Rape/prevention & control ; *Empowerment ; Meta-Analysis as Topic ; }, } @article {pmid38103278, year = {2024}, author = {Kowalik, BA and Delfabbro, PH and King, DL}, title = {Impaired control and gaming-related harm in relation to gaming Disorder.}, journal = {Addictive behaviors}, volume = {151}, number = {}, pages = {107926}, doi = {10.1016/j.addbeh.2023.107926}, pmid = {38103278}, issn = {1873-6327}, mesh = {Humans ; *Behavior, Addictive/psychology ; *Video Games/psychology ; *Gambling/psychology ; Surveys and Questionnaires ; *Psychological Distress ; Internet ; }, abstract = {The concept of impaired control (IC) over gaming is an important element of assessment and interventions for problem gaming and gaming-related harm. Past studies have reported that gaming disorder (GD) is associated with various negative consequences, but there is limited research on the relationship between IC over gaming and negative outcomes. To address this gap, the study investigated the relationship between impaired control and gaming-related harm among individuals with self-identified gaming disorder. It was hypothesized that IC would be positively associated with gaming-related harm and harm severity. In addition, it was predicted that IC would be a significant predictor of harm when controlling for age, gender, psychological distress, and gaming urges. The current study recruited 513 participants through an online survey platform. The Impaired Control Over Gaming Scale (ICOGS) was used to measure IC, and modified items from Browne et al.'s taxonomy of gambling harms were used to assess gaming harm severity. The logistic regression results showed that IC was positively related to all forms of harm, after controlling for other variables. The predictive value of IC was similar across financial, psychological, relationship, social and work/school domains. These results supported the importance of IC as a mechanism that contributes to the experience of gaming-related harm, and the need to target IC in interventions for GD.}, } @article {pmid38102945, year = {2024}, author = {Bhamra, IB and Gallagher, JE and Patel, R}, title = {Telehealth technologies in care homes: a gap for dentistry?.}, journal = {Journal of public health (Oxford, England)}, volume = {46}, number = {1}, pages = {e106-e135}, pmid = {38102945}, issn = {1741-3850}, mesh = {Humans ; *Telemedicine ; *Remote Consultation ; Delivery of Health Care ; Health Facilities ; Dentistry ; }, abstract = {BACKGROUND: Telehealth technologies are playing an increasing role in healthcare. This study aimed to review the literature relating to the use of telehealth technologies in care homes with a focus on teledentistry.

METHODS: Khangura et al.'s (Evidence summaries: the evolution of a rapid review approach. Syst Rev 2012;1:10) rapid review method included an electronic database search on Embase, PubMed, Web of Science and OpenGrey. Out of 1525 papers, 1108 titles and abstracts were screened, and 75 full texts assessed for eligibility. Risk of bias was assessed using the Mixed Methods Assessment Tool 2018.

RESULTS: Forty-seven papers (40 studies) from 10 countries, published 1997-2021, were included in the review, four studies related to teledentistry. Whilst some preferred in-person consultations, perceived benefits by stakeholders included reduced hospitalization rates (n = 14), cost-savings (n = 8) and high diagnostic accuracy (n = 7). Studies investigating teledentistry using intra-oral cameras reported that teleconsultations were feasible with potentially high diagnostic accuracy (n = 2), cost-savings (n = 1) and patient acceptability (n = 1).

CONCLUSION: There is limited published research on teledentistry, but wider telehealth research is applicable to teledentistry, with findings suggesting that telehealth technologies play a role in care homes consultations that are acceptable, cost-saving and with potential diagnostic accuracy. Further research is needed on the mode, utility and acceptability of teledentistry in care homes.}, } @article {pmid38102783, year = {2024}, author = {Barger, B}, title = {Epidemiology with psychometric spirit: MoBa leads autism's interdisciplinary future-a commentary on Havdahl et al. (2023).}, journal = {Journal of child psychology and psychiatry, and allied disciplines}, volume = {65}, number = {8}, pages = {1115-1118}, doi = {10.1111/jcpp.13933}, pmid = {38102783}, issn = {1469-7610}, support = {90DD0662//Center for Leadership in Disability as a University Center for Excellence in Developmental Disabilities. Administration on Intellectual and Developmental Disabilities/ ; }, mesh = {Humans ; *Psychometrics/standards/instrumentation ; Norway ; Child ; Autistic Disorder/psychology ; Autism Spectrum Disorder ; Longitudinal Studies ; }, abstract = {Havdahl et al.'s (2023) Norwegian Mother, Father and Child Cohort Study (MoBa) skill loss study stands out for their creative consideration of scale items to gain a better understanding of skill loss/regression. This commentary outlines how the MoBa team continues to challenge the field by conducting "basic" measurement analyses with their public health longitudinal population data. Their creative use of items, validity-oriented analyses, and transparent reporting of item correlations emulates early-stage scale development in psychometric research, and sets the stage for considering how psychometricians and epidemiologists might more directly work with each other to improve early autism identification research.}, } @article {pmid38100009, year = {2024}, author = {Zhao, DW and Robinson, SG and Pozzar, R and Leiter, R and Walsh, C and Siemens, I and Lovrics, E and Cellarius, V and Mahtani, R and Jia, Z}, title = {The Evolving Roles and Expectations of Inpatient Palliative Care Through COVID-19: a Systematic Review and Meta-synthesis.}, journal = {Journal of general internal medicine}, volume = {39}, number = {4}, pages = {661-682}, pmid = {38100009}, issn = {1525-1497}, mesh = {Humans ; *COVID-19/therapy/epidemiology/psychology ; *Palliative Care/methods ; Inpatients/psychology ; SARS-CoV-2 ; }, abstract = {BACKGROUND: Palliative care performed a central role in responding to the systemic suffering incurred by the COVID-19 pandemic. Yet, few studies have elucidated the inpatient palliative care specialists' experiences and perceptions.

OBJECTIVE: Systematically review and synthesize the evolving roles and expectations of inpatient palliative care specialists in response to COVID-19.

DESIGN: A systematic review and meta-synthesis informed by Thomas and Harden's framework and Pozzar et al.'s approach was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines.

DATA SOURCES: MEDLINE, EMBASE, CINAHL, and PubMed were systematically searched for articles published between December 2019 and March 2023. We included all peer-reviewed qualitative and mixed-method literature studying the roles and expectations of inpatient palliative care specialists. A mixed-method appraisal tool was used for quality assessment.

RESULTS: Of 3869 unique articles, 52 were included. Studies represented North American (n = 23), European (n = 16), South American (n = 4), Oceanic (n = 2), Asian (n = 2), West African (n = 1), Middle Eastern (n = 1), and inter-continental settings (n = 3). Most were reported in English (n = 50), conducted in 2020 (n = 28), and focused on the perspectives of inpatient palliative care clinicians (n = 28). Three descriptive themes captured the roles and expectations of inpatient palliative care specialists: shifting foundations, reorienting to relationships, and evolving identity. Two analytical themes were synthesized: palliative care propagates compassion through a healing presence, and palliative care enhances the systemic response to suffering through nimble leadership.

CONCLUSION: Inpatient palliative care specialists responded to the COVID-19 pandemic by establishing their healing presence and leading with their adaptability. To develop institutionally tailored and collaborative responses to future pandemics, future studies are needed to understand how inpatient palliative care clinicians are recognized and valued within their institutions.}, } @article {pmid38087299, year = {2023}, author = {Brehon, K and Miciak, M and Hung, P and Chen, SP and Perreault, K and Hudon, A and Wieler, M and Hunter, S and Hoddinott, L and Hall, M and Churchill, K and Brown, DA and Brown, CA and Bostick, G and Skolnik, K and Lam, G and Weatherald, J and Gross, DP}, title = {"None of us are lying": an interpretive description of the search for legitimacy and the journey to access quality health services by individuals living with Long COVID.}, journal = {BMC health services research}, volume = {23}, number = {1}, pages = {1396}, pmid = {38087299}, issn = {1472-6963}, support = {466857/CAPMC/CIHR/Canada ; 466857/CAPMC/CIHR/Canada ; }, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; Qualitative Research ; *COVID-19/epidemiology ; Health Services ; Delivery of Health Care ; Health Services Accessibility ; }, abstract = {BACKGROUND: Understanding of Long COVID has advanced through patient-led initiatives. However, research about barriers to accessing Long COVID services is limited. This study aimed to better understand the need for, access to, and quality of, Long COVID services. We explored health needs and experiences of services, including ability of services to address needs.

METHODS: Our study was informed by the Levesque et al.'s (2013) "conceptual framework of access to health care." We used Interpretive Description, a qualitative approach partly aimed at informing clinical decisions. We recruited participants across five settings. Participants engaged in one-time, semi-structured, virtual interviews. Interviews were transcribed verbatim. We used reflexive thematic analysis. Best practice to ensure methodological rigour was employed.

RESULTS: Three key themes were generated from 56 interviews. The first theme illustrated the rollercoaster-like nature of participants' Long COVID symptoms and the resulting impact on function and health. The second theme highlighted participants' attempts to access Long COVID services. Guidance received from healthcare professionals and self-advocacy impacted initial access. When navigating Long COVID services within the broader system, participants encountered barriers to access around stigma; appointment logistics; testing and 'normal' results; and financial precarity and affordability of services. The third theme illuminated common factors participants liked and disliked about Long COVID services. We framed each sub-theme as the key lesson (stemming from all likes and dislikes) that, if acted upon, the health system can use to improve the quality of Long COVID services. This provides tangible ways to improve the system based directly on what we heard from participants.

CONCLUSION: With Long COVID services continuously evolving, our findings can inform decision makers within the health system to better understand the lived experiences of Long COVID and tailor services and policies appropriately.}, } @article {pmid38079579, year = {2024}, author = {Stefánsdóttir, H and Crowe, K and Magnússon, E and Guiberson, M and Másdóttir, T and Ágústsdóttir, I and Baldursdóttir, ÖV}, title = {Measuring speech intelligibility with deaf and hard-of-hearing children: A systematic review.}, journal = {Journal of deaf studies and deaf education}, volume = {29}, number = {2}, pages = {265-277}, pmid = {38079579}, issn = {1465-7325}, mesh = {Humans ; *Speech Intelligibility/physiology ; Child ; *Deafness/psychology ; Persons with Hearing Disabilities/psychology ; }, abstract = {There is great variability in the ways in which the speech intelligibility of d/Deaf and hard-of-hearing (DHH) children who use spoken language as part, or all, of their communication system is measured. This systematic review examined the measures and methods that have been used when examining the speech intelligibility of children who are DHH and the characteristics of these measures and methods. A systematic database search was conducted of CENTRAL; CINAHL; Cochrane; ERIC; Joanna Briggs; Linguistics, Language and Behavior Abstracts; Medline; Scopus; and Web of Science databases, as well as supplemental searches. A total of 204 included studies reported the use of many different measures/methods which measured segmental aspects of speech, with the most common being Allen et al.'s (2001, The reliability of a rating scale for measuring speech intelligibility following pediatric cochlear implantation. Otology and Neurotology, 22(5), 631-633. https://doi.org/10.1097/00129492-200109000-00012) Speech Intelligibility Rating scale. Many studies included insufficient details to determine the measure that was used. Future research should utilize methods/measures with known psychometric validity, provide clear descriptions of the methods/measures used, and consider using more than one measure to account for limitations inherent in different methods of measuring the speech intelligibility of children who are DHH, and consider and discuss the rationale for the measure/method chosen.}, } @article {pmid38076288, year = {2023}, author = {Bray, EA and George, A and Everett, B and Salamonson, Y and Ramjan, LM}, title = {Feasibility and Acceptability of a Codesigned Health Care Transition Intervention for Young People With Spinal Cord Injuries.}, journal = {Topics in spinal cord injury rehabilitation}, volume = {29}, number = {3}, pages = {89-97}, pmid = {38076288}, issn = {1945-5763}, mesh = {Adult ; Humans ; Child ; Adolescent ; *Spinal Cord Injuries/complications ; Feasibility Studies ; *Transition to Adult Care ; Patient Transfer ; Caregivers ; }, abstract = {BACKGROUND: Due in part to medical complications, adults with a pediatric onset spinal cord injury (SCI) are at higher risk of experiencing dissatisfaction with life and lower perceived physical health when compared to their peers with no disability. To support the prevention of medical complications, young people with SCI must successfully transition to adult health care. Health care transition (HCT) interventions can support young people with chronic conditions in their move to adult health care.

OBJECTIVES: To evaluate the feasibility and acceptability of a web-based HCT intervention codesigned with young people with SCI and parents/caregivers.

METHODS: Semi-structured individual interviews were conducted online with young people with SCI and parents/caregivers who transitioned or were preparing for the transition from pediatric to adult health care. Interviews were also conducted with health care professionals. The interviews were analyzed using a hybrid deductive and inductive qualitative content analysis process. Feasibility and acceptability were measured using Bowen and colleagues' framework, which includes eight focus areas: acceptability, demand, implementation, practicality, adaption, integration, expansion, and limited efficacy.

RESULTS: Overall, participants responded positively to the intervention and believed that it would be useful to young people with SCI and parents/caregivers. Two areas of Bowen et al.'s framework, implementation and integration, require further consideration in terms of how to embed the intervention into the current transition process.

CONCLUSION: This study found the HCT intervention to be an innovative approach to support young people with SCI and their parent/caregivers that demonstrates promise in the areas of feasibility and acceptability.}, } @article {pmid38073361, year = {2024}, author = {Kaleeny, J and Janis, J}, title = {Correspondence: Morphological features of the greater occipital nerve and its possible importance for interventional procedures.}, journal = {Journal of anatomy}, volume = {244}, number = {4}, pages = {676-677}, pmid = {38073361}, issn = {1469-7580}, mesh = {Humans ; *Spinal Nerves ; *Headache ; }, abstract = {This response applauds Saglam et al.'s (2023) recent study on the greater occipital nerve's anatomy while urging readers to consider earlier pivotal studies overlooked. It emphasizes how prior research has significantly shaped headache treatments and provides valuable insights for future practices and discussions.}, } @article {pmid38072634, year = {2024}, author = {Su, X and Jin, X and Wang, Z and Duan, S}, title = {Unraveling Exogenous DNA Processing in Cas4-Lacking Crispr Systems: A Novel Bypass Pathway Explored.}, journal = {Advanced biology}, volume = {8}, number = {3}, pages = {e2300454}, doi = {10.1002/adbi.202300454}, pmid = {38072634}, issn = {2701-0198}, support = {210000-581835//Qiantang Scholars Fund in Hangzhou City University/ ; }, mesh = {*CRISPR-Cas Systems/genetics ; *CRISPR-Associated Proteins/genetics/metabolism ; DNA/genetics/metabolism ; }, abstract = {Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) systems are widely distributed adaptive immune systems found in prokaryotes. The process involves three main stages: adaptation, expression, and interference. While the adaptation stage has been extensively studied, there is still an incomplete understanding of the mechanisms underlying the capture, trimming, and integration of exogenous DNA. For instance, Cas4, a CRISPR-Cas protein with endonuclease activity, is responsible for selecting and processing protospacer adjacent motif (PAM) sequences. However, some CRISPR isoforms lack Cas4 activity, relying on other enzymes for adaptive immunity. Recently, Wang et al. presented a novel model of exogenous DNA processing in a type I-E CRISPR system lacking Cas4 in a Nature article. This model integrates protospacer processing into CRISPR arrays through fine-tuned synthases formed by DnaQ-like exonuclease (DEDDh) and Cas1-Cas2 complexes. Their study introduces a novel model, shedding new light on the evolution of CRISPR adaptive immunity. This perspective comprehensively examines the fundamental process of CRISPR adaptive immunity, detailing both the classical pathway mediated by Cas4 and the alternative pathway mediated by DEDDh. Furthermore, a thorough evaluation of Wang et al.'s work is conducted, highlighting its strengths, weaknesses, and existing research challenges.}, } @article {pmid38062267, year = {2024}, author = {Kolak, M and Kızılgöz, V and Kantarci, M}, title = {Examination of ethmoidal roof regarding Keros and Yenigun classifications in a Turkish population: a computerized tomography study.}, journal = {Surgical and radiologic anatomy : SRA}, volume = {46}, number = {1}, pages = {19-25}, pmid = {38062267}, issn = {1279-8517}, mesh = {Male ; Humans ; Female ; Retrospective Studies ; Turkey ; *Ethmoid Bone/diagnostic imaging/anatomy & histology ; Tomography, X-Ray Computed ; *Paranasal Sinuses/anatomy & histology ; Ethmoid Sinus/diagnostic imaging/surgery/anatomy & histology ; }, abstract = {PURPOSE: Understanding ethmoid roof morphology is crucial to prevent complications in endoscopic sinus surgery. This study aimed to evaluate the morphological properties of the ethmoidal roof regarding gender and age differences using Keros and Yenigun classifications on high-resolution computed tomography images.

METHODS: We retrospectively analyzed 891 high-resolution computed tomography paranasal sinus study images and measured the depth of the cribriform plate in coronal sections and the anterior-posterior length in axial planes. The study retrospectively examined CT images of paranasal sinuses of patients living in the eastern Anatolian region of Turkey.

RESULTS: In both Keros and Yenigun Classifications, the most common class was type 2, and the least common class was type 3. According to Keros et al.'s method, no significant difference was observed between men and women (p = 0.698). However, according to Yenigun et al., the average values of women in terms of the anterior-posterior distance of the ethmoid roof were significantly higher than men (p = 0.001). When examined according to age, a very low, negative correlation was revealed regarding Keros and Yenigun classifications (p = 0.047 and p < 0.001 retrospectively). According to Keros and Yenigun's classification, there was no significant difference between the left and right sides (p = 0.488 and p = 0.919, respectively).

CONCLUSION: The morphological properties of the ethmoidal roof have importance to be considered for preoperative planning. Studying larger patient groups and meta-analyses that gather various research results about this subject might help better understand the ethmoidal roof morphology among populations.}, } @article {pmid38057777, year = {2023}, author = {Pellowski, JA and Jensen, D and Tsawe, N and Colvin, C and Cu-Uvin, S and Operario, D and Lurie, M and Harrison, A and Myer, L and Knight, L}, title = {Womandla Health: development and rationale of a behavioral intervention to support HIV treatment adherence among postpartum women in South Africa.}, journal = {BMC women's health}, volume = {23}, number = {1}, pages = {649}, pmid = {38057777}, issn = {1472-6874}, support = {K01 MH112443/MH/NIMH NIH HHS/United States ; R25 MH067127/MH/NIMH NIH HHS/United States ; K01MH112443/MH/NIMH NIH HHS/United States ; }, mesh = {Pregnancy ; Female ; Humans ; *HIV Infections/drug therapy/psychology ; South Africa ; Medication Adherence/psychology ; Postpartum Period/psychology ; Anti-Retroviral Agents/therapeutic use ; *Pregnancy Complications, Infectious/drug therapy ; Treatment Adherence and Compliance ; Infectious Disease Transmission, Vertical/prevention & control ; *Anti-HIV Agents/therapeutic use ; }, abstract = {BACKGROUND: While Option B + has made great strides in eliminating vertical transmission of HIV and improving access to lifelong antiretroviral therapy (ART) for women, the postpartum period remains a risk period for disengagement from HIV care and non-adherence.

METHODS: Longitudinal qualitative data was collected from 30 women living with HIV in Cape Town, South Africa from pregnancy through 1 year postpartum to examine key barriers and facilitators to HIV treatment adherence across this transition. Participants were also asked about their preferences for behavioral intervention content, format, and scope. The intervention development process was guided by Fernandez et al.'s Intervention Mapping process and was informed by the qualitative data, the wider literature on ART adherence, and Transition Theory.

RESULTS: The Womandla Health Intervention is a multicomponent intervention consisting of four individual sessions with a lay health worker and four peer group sessions, which span late pregnancy and early postpartum. These sessions are guided by Transition Theory and utilize motivational interviewing techniques to empower women to ascertain their own individual barriers to HIV care and identify solutions and strategies to overcome these barriers.

CONCLUSIONS: This intervention will be tested in a small scale RCT. If successful, findings will provide an innovative approach to HIV treatment by capitalizing on the transition into motherhood to bolster self-care behaviors, focusing on ART adherence and also women's overall postpartum health and psychosocial needs.}, } @article {pmid38054285, year = {2023}, author = {Lin, H}, title = {The scientific value of explanation and prediction.}, journal = {The Behavioral and brain sciences}, volume = {46}, number = {}, pages = {e399}, doi = {10.1017/S0140525X23001735}, pmid = {38054285}, issn = {1469-1825}, mesh = {Humans ; *Neural Networks, Computer ; *Knowledge ; }, abstract = {Deep neural network models have revived long-standing debates on the value of explanation versus prediction for advancing science. Bowers et al.'s critique will not make these models go away, but it is likely to prompt new work that seeks to reconcile explanatory and predictive models, which could change how we determine what constitutes valuable scientific knowledge.}, } @article {pmid38051457, year = {2024}, author = {Delmas, H and Ciocan, C and Novopashyna, M and Paeye, C}, title = {Resistance of a short-term memory concealed information test with famous faces to countermeasures.}, journal = {Memory & cognition}, volume = {52}, number = {3}, pages = {632-647}, pmid = {38051457}, issn = {1532-5946}, mesh = {Humans ; *Memory, Short-Term ; *Recognition, Psychology/physiology ; Eye Movements ; Cognition ; Pattern Recognition, Visual/physiology ; }, abstract = {The concealed information test (CIT) aims at identifying knowledge that a person wants to hide, by measuring physiological indices during the presentation of known versus unknown items. Recently, Lancry-Dayan et al. (Journal of Applied Research in Memory and Cognition, 7 (2), 291-302, 2018) proposed a new version of this test that included a short-term memory task to maximize differences between responses to items. Participants were asked to memorize four pictures of faces that included one face of an acquaintance. The authors observed that participants looked at the familiar face during the first second and then tended to avoid it. This specific orientation-avoidance pattern occurred even in participants instructed to conceal their familiarity with the known faces (in a spontaneous or a guided manner). In a first experiment, we reproduced Lancry-Dayan et al.'s (2018) study using photos of famous faces. The pattern found by Lancry-Dayan et al. was observed in participants asked to perform the memory task only, participants asked to conceal their familiarity with the famous faces, and participants of a countermeasure group. In a second experiment, we tested the robustness of Lancry-Dayan et al.'s countermeasure. We modified the instructions by emphasizing the oculomotor task or giving feedback. While between-group differences in gaze-pattern appeared after feedback was provided, classification analyses were still able to distinguish between familiar and unfamiliar faces accurately, which revealed the good resistance of this new CIT protocol to countermeasures.}, } @article {pmid38049900, year = {2023}, author = {Flynn, R and Cassidy, C and Dobson, L and Al-Rassi, J and Langley, J and Swindle, J and Graham, ID and Scott, SD}, title = {Knowledge translation strategies to support the sustainability of evidence-based interventions in healthcare: a scoping review.}, journal = {Implementation science : IS}, volume = {18}, number = {1}, pages = {69}, pmid = {38049900}, issn = {1748-5908}, mesh = {Humans ; *Translational Science, Biomedical ; *Evidence-Based Medicine ; Delivery of Health Care ; }, abstract = {BACKGROUND: Knowledge translation (KT) strategies are widely used to facilitate the implementation of EBIs into healthcare practices. However, it is unknown what and how KT strategies are used to facilitate the sustainability of EBIs in institutional healthcare settings.

OBJECTIVES: This scoping review aimed to consolidate the current evidence on (i) what and how KT strategies are being used for the sustainability of EBIs in institutional healthcare settings; (ii) the reported KT strategy outcomes (e.g., acceptability) for EBI sustainability, and (iii) the reported EBI sustainability outcomes (e.g., EBI activities or component of the intervention continue).

METHODS: We conducted a scoping review of five electronic databases. We included studies describing the use of specific KT strategies to facilitate the sustainability of EBIs (more than 1-year post-implementation). We coded KT strategies using the clustered ERIC taxonomy and AIMD framework, we coded KT strategy outcomes using Tierney et al.'s measures, and EBI sustainability outcomes using Scheirer and Dearing's and Lennox's taxonomy. We conducted descriptive numerical summaries and a narrative synthesis to analyze the results.

RESULTS: The search identified 3776 studies for review. Following the screening, 25 studies (reported in 27 papers due to two companion reports) met the final inclusion criteria. Most studies used multi-component KT strategies for EBI sustainability (n = 24). The most common ERIC KT strategy clusters were to train and educate stakeholders (n = 38) and develop stakeholder interrelationships (n = 34). Education was the most widely used KT strategy (n = 17). Many studies (n = 11) did not clearly report whether they used different or the same KT strategies between EBI implementation and sustainability. Seven studies adapted KT strategies from implementation to sustainability efforts. Only two studies reported using a new KT strategy for EBI sustainability. The most reported KT strategy outcomes were acceptability (n = 10), sustainability (n = 5); and adoption (n = 4). The most commonly measured EBI sustainability outcome was the continuation of EBI activities or components (n = 23), followed by continued benefits for patients, staff, and stakeholders (n = 22).

CONCLUSIONS: Our review provides insight into a conceptual problem where initial EBI implementation and sustainability are considered as two discrete time periods. Our findings show we need to consider EBI implementation and sustainability as a continuum and design and select KT strategies with this in mind. Our review has emphasized areas that require further research (e.g., KT strategy adaptation for EBI sustainability). To advance understanding of how to employ KT strategies for EBI sustainability, we recommend clearly reporting the dose, frequency, adaptations, fidelity, and cost of KT strategies. Advancing our understanding in this area would facilitate better design, selection, tailored, and adapted use of KT strategies for EBI sustainability, thereby contributing to improved patient, provider, and health system outcomes.}, } @article {pmid38047911, year = {2023}, author = {Nobes, G}, title = {Daly and colleagues have overestimated the magnitude of the "Cinderella effect" in lethal child abuse, and underestimated the role of confounding variables in its explanation: A reply to Daly (2022).}, journal = {Journal of experimental psychology. General}, volume = {152}, number = {12}, pages = {3599-3604}, doi = {10.1037/xge0001501}, pmid = {38047911}, issn = {1939-2222}, mesh = {*Family Structure ; *Age Factors ; Male ; White People ; Adolescent ; Child ; Fathers ; Humans ; European People ; *Child Abuse/mortality ; Child, Preschool ; Confounding Factors, Epidemiologic ; Homicide ; }, abstract = {Nobes et al. (2019) used updated data from the same source-the British Home Office's Homicide Index-as that used by Daly and Wilson (1994) to investigate the Cinderella effect (increased risk to stepchildren), and in particular their claim (e.g., Daly, 2022; Daly & Wilson, 1994, 2001, 2008) that stepfathers fatally assault their young children at rates more than 100 times those of genetic fathers. Nobes et al. reported much lower-though still substantial-increased risk to young stepchildren, and little or none to older children, particularly when they took the mislabeling of noncohabiting perpetrators into account. In his Commentary, Daly (2022) largely accepts this analysis, but does not acknowledge its implications for his own findings and claims. Nobes et al. also reported that controlling for father's age accounted for much of the remaining increased risk, and argued that this and other confounding variables are likely to explain most or all of the Cinderella effect. Daly says very little about this too, but instead responds with a series of criticisms, many of which misrepresent Nobes et al.'s account, and most of which are incorrect. Young stepchildren are at increased risk, but if stepparenthood per se (i.e., lack of genetic relatedness) contributes to the explanation, its influence is considerably less than Daly claims. (PsycInfo Database Record (c) 2023 APA, all rights reserved).}, } @article {pmid38047910, year = {2023}, author = {Wood, W and Mazar, A}, title = {Habits are not goal-dependent: Commentary on Buabang et al. (2023).}, journal = {Journal of experimental psychology. General}, volume = {152}, number = {12}, pages = {3594-3598}, doi = {10.1037/xge0001502}, pmid = {38047910}, issn = {1939-2222}, mesh = {Humans ; *Cues ; *Habits ; }, abstract = {People sometimes commit action slips by absentmindedly repeating unwanted responses, such as entering an old password instead of the current one. Most accounts hold that such slips demonstrate stimulus-response habits in which familiar contexts directly trigger well-practiced but now-incorrect responses. In contrast, Buabang et al. (2023) argue that action slips arise due to the continued influence of old, no longer accurate goal outcomes. In a reanalysis, we show that Buabang et al.'s participants actually provide striking evidence of goal-independent S-R habits: They correctly repeated well-practiced responses despite reporting incorrect goals. We also show that Buabang et al. misinterpreted the results of their mediation analyses by overlooking the direct influence of stimuli on responses. Understanding how habits work is important because habit change interventions are unlikely to succeed with goal-directed strategies that overlook context cues' direct activation of practiced responses. (PsycInfo Database Record (c) 2023 APA, all rights reserved).}, } @article {pmid38047437, year = {2024}, author = {Muroi, D and Kodama, K and Tomono, T and Saito, Y and Koyake, A and Higuchi, T}, title = {Approaching Process in Walking through an Aperture for Individuals with Stroke.}, journal = {Journal of motor behavior}, volume = {56}, number = {2}, pages = {139-149}, doi = {10.1080/00222895.2023.2280259}, pmid = {38047437}, issn = {1940-1027}, mesh = {Humans ; Walking ; *Stroke/complications ; *Stroke Rehabilitation/methods ; Biomechanical Phenomena ; }, abstract = {Muroi et al. show that individuals with stroke have improved collision avoidance behavior when passing through an aperture while entering from the paretic-side of the body. However, the underlying mechanism remains unknown. We reanalyzed Muroi et al.'s data to reveal how individuals with stroke walk through an aperture by examining changes in walking velocity and behavioral complexity (i.e., sample entropy, an index of (ir)regularity of time series, regarded lower entropy as more regular and less complex) by focusing on the approaching process. The results showed that individuals with stroke reduced their walking velocity and behavioral complexity before passing through the narrow aperture when approaching from the paretic side. We interpreted that the improved obstacle avoidance when penetrating from the paretic side may be due to careful body rotation and adjusting the walking velocity in advance.}, } @article {pmid38041985, year = {2024}, author = {Kumar, N and Rauf, SA and Riya, and Arbab, S}, title = {Commentary on "Relationship between miRNA-21, miRNA-155, and miRNA-182 expression and inflammatory factors in cerebrospinal fluid from patients with multiple sclerosis".}, journal = {Clinical neurology and neurosurgery}, volume = {236}, number = {}, pages = {108054}, doi = {10.1016/j.clineuro.2023.108054}, pmid = {38041985}, issn = {1872-6968}, mesh = {Humans ; *Multiple Sclerosis/diagnosis ; Biomarkers/cerebrospinal fluid ; *MicroRNAs/genetics/metabolism ; *Persons with Disabilities ; }, abstract = {This letter provides insightful perspectives on multiple sclerosis (MS) biomarkers, building upon Behrouz Shademan et al.'s study on miRNA-21, miRNA-155, and miRNA-182 [1]. Beyond these miRNAs, we delve into recent advancements, highlighting promising biomarkers such as ELTD1, CHI3L1, and Fecal Lcn-2. ELTD1 exhibits potential for MS diagnosis, CHI3L1 correlates with disability aspects, and Fecal Lcn-2 serves as a sensitive indicator for gut dysbiosis. Our exploration underscores the evolving landscape of MS biomarker research, urging further investigation for integrating these new markers into diagnostic and monitoring strategies.}, } @article {pmid38039863, year = {2024}, author = {Dotov, D and Paxton, A}, title = {Grounding social timing: A commentary on "The evolution of social timing" by Verga et al. (2023).}, journal = {Physics of life reviews}, volume = {48}, number = {}, pages = {8-10}, doi = {10.1016/j.plrev.2023.11.005}, pmid = {38039863}, issn = {1873-1457}, abstract = {We are excited about Verga et al.'s [22] exhortation to look beyond humans to understand the purpose, scope, and evolution of social timing. We argue that the field should expand even further. We first point out the enabling role of the spatial environment, which constrains social interaction and in which social interaction is embedded. Second, we argue that a full appreciation of the emergence of social timing must include a focus on physical prerequisites of interactive systems, exemplified by studies of dissipative structures more broadly. By situating interacting systems-whether biological or not-within their shared dynamic environment, we can more clearly and more fully understand social timing.}, } @article {pmid38033517, year = {2023}, author = {Ludlow, K and Russell, JK and Ryan, B and Brown, RL and Joynt, T and Uhlmann, LR and Smith, GE and Donovan, C and Hides, L and Spence, SH and March, S and Cobham, VE}, title = {Co-designing a digital mental health platform, "Momentum", with young people aged 7-17: A qualitative study.}, journal = {Digital health}, volume = {9}, number = {}, pages = {20552076231216410}, pmid = {38033517}, issn = {2055-2076}, abstract = {INTRODUCTION: Digital mental health interventions (DMHIs) offer a promising alternative or adjunct treatment method to face-to-face treatment, overcoming barriers associated with stigma, access, and cost. This project is embedded in user experience and co-design to enhance the potential acceptability, usability and integration of digital platforms into youth mental health services.

OBJECTIVE: To co-design a digital mental health platform that provides self-directed, tailored, and modularised treatment for young people aged 7-17 years experiencing anxiety, depression and other related problems.

METHODS: Sixty-eight participants, aged 7-17 years, engaged in one of 20 co-design workshops. Eight workshops involved children (n  =  26, m  =  9.42 years, sd  =  1.27) and 12 involved adolescents (n  =  42, m  =  14.57 years, sd  =  1.89). Participants engaged in a variety of co-design activities (e.g., designing a website home page and rating self-report assessment features). Workshop transcripts and artefacts (e.g., participants' drawings) were thematically analysed using Gale et al.'s Framework Method in NVivo.

RESULTS: Six themes were identified: Interactive; Relatable; Customisable; Intuitive; Inclusive; and Personalised, transparent and trustworthy content. The analysis revealed differences between children's and adolescents' designs and ideas, supporting the need for two different versions of the platform, with age-appropriate activities, features, terminology, and content.

CONCLUSIONS: This research showcased co-design as a powerful tool to facilitate collaboration with young people in designing DMHIs. Two sets of recommendations were produced: 1) recommendations for the design, functionality, and content of youth DMHIs, supported by child- and adolescent-designed strategies; and 2) recommendations for clinicians and researchers planning to conduct co-design and intervention development research with children and adolescents.}, } @article {pmid38028947, year = {2023}, author = {Kenney, EL and Poole, MK and Frost, N and Kinderknecht, K and Mozaffarian, RS and Andreyeva, T}, title = {How policy implementation shapes the impact of U.S. food assistance policies: the case study of the Child and Adult Care Food Program.}, journal = {Frontiers in health services}, volume = {3}, number = {}, pages = {1286050}, pmid = {38028947}, issn = {2813-0146}, support = {K01 DK125278/DK/NIDDK NIH HHS/United States ; T32 HL098048/HL/NHLBI NIH HHS/United States ; }, abstract = {Much of the chronic disease burden in the U.S. population can be traced to poor diet. There has been a sustained focus on influencing children's diets and encouraging healthier eating habits by changing policies for what foods and beverages can be served to children through large federally-funded nutrition assistance programs. Yet without attention to how nutrition policies are implemented, and the surrounding context for these policies, these policy changes may not have the intended results. In this perspective, we used Bullock et al.'s (2021) Process Model of Implementation from a Policy Perspective to analyze how the complexities of the implementation process of large-scale nutrition policies can dilute potential health outcomes. We examine the Child and Adult Care Food Program (CACFP), a federal program focused on supporting the provision of nutritious meals to over 4 million children attending childcare, as a case study. We examine how the larger societal contexts of food insecurity, attitudes towards the social safety net, and a fragmented childcare system interact with CACFP. We review the "policy package" of CACFP itself, in terms of its regulatory requirements, and the various federal, state, and local implementation agencies that shape CACFP's on-the-ground implementation. We then review the evidence for how each component of the CACFP policy implementation process impacts uptake, costs, feasibility, equity, and effectiveness at improving children's nutrition. Our case study demonstrates how public health researchers and practitioners must consider the complexities of policy implementation processes to ensure effective implementation of nutrition policies intended to improve population health.}, } @article {pmid38023780, year = {2023}, author = {Cassivi, C and Blanchet Garneau, A}, title = {More than juxtaposition: a commentary to Willis et al.'s (2023) mixed method study on mobile mental health interventions.}, journal = {mHealth}, volume = {9}, number = {}, pages = {38}, pmid = {38023780}, issn = {2306-9740}, } @article {pmid38022788, year = {2023}, author = {Garland, WJ and Smith, KL and Dixon, JC and Horton, S}, title = {Developmental activities of elite junior hockey players: an analysis of early sport specialization.}, journal = {Frontiers in sports and active living}, volume = {5}, number = {}, pages = {1253007}, pmid = {38022788}, issn = {2624-9367}, abstract = {Early sport specialization is a popular and contentious topic in the scientific literature and popular media. The lure of extrinsic rewards has led to increasing rates of specialization among young athletes, while expert recommendations promote multisport participation. The purpose of this study was to describe and analyze developmental activities of a group of elite junior hockey players in Canada. Within this context, elements of specialization were investigated in accordance with existing theoretical frameworks and long-term athlete development models to enhance the literature. Fifteen participants from the Ontario Hockey League completed quantitative retrospective interviews, detailing past sport and recreational activities. Thirty-one developmental milestones were assessed. Accumulated hours of activity were categorized in accordance with Côté's (1999) Developmental Model of Sports Participation, along with the number and types of sports in which they participated during childhood. Jayanthi et al.'s (2015) continuum was utilized to determine the age at which the athletes became moderately and highly specialized. Accrued hours of deliberate practice reported by participants increased from ages 6 to 16 years, as did competition in organized hockey games. Reported hours of deliberate play peaked at 9 years of age and decreased thereafter. Participants played a combined 16 sports other than hockey, ranging from an average of 2.0 at age 6, to a maximum average of 5.6 at 12 years old, and decreasing each year to 2.3 by age 15. The greatest number of hours in other sports was accumulated at 12 years of age. Using a three-point scale, participants considered themselves "highly specialized" at 14 years old; however, other quantitative indicators suggested this may have occurred at 12 years of age. Relative to previous research on early sport specialization, participants in this study spent more time practicing hockey, while ceasing hockey-specific play and other sports at younger ages. Despite a diverse sport history, hockey competition was initiated earlier than recommended, showing high levels of sport commitment as young as 9 years old. The early specialization path remains a popular trajectory among coaches, parents, and athletes in Canadian ice hockey.}, } @article {pmid38019902, year = {2023}, author = {Lackner, CL and Wang, CH}, title = {Predictors of Intention to Vaccinate or Continue to Vaccinate Children Against SARS-CoV-2 During the Fifth Wave of the COVID-19 Pandemic in the USA.}, journal = {Psychological reports}, volume = {}, number = {}, pages = {332941231219644}, doi = {10.1177/00332941231219644}, pmid = {38019902}, issn = {1558-691X}, abstract = {The Centre for Disease Control recommends vaccination of children against SARS-CoV-2 to reduce the severity of COVID-19 disease and reduce the likelihood of associated complications. Vaccination of children requires the consent of parents or guardians, and levels of consent may ebb and flow over the course of the pandemic. This exploratory study examines predictors of parental intentions to vaccinate their children and the speed with which they would have them vaccinated during the fifth wave of the pandemic when vaccines were just being approved for use in children using a convenience sample of 641 parents reporting on 962 children. Multi-level regression analyses demonstrated regional differences in likelihood, with those in the Northeast reporting higher likelihood than those in the West. Parents with a conservative belief system were less likely to want to have their children vaccinated. Parents were more likely to have their child vaccinated if the child had COVID-19-related health risks, their child had a more complete vaccination history, and COVID-19 was perceived to be a greater threat to oneself and one's family. Faster intended vaccination speed was associated with regional urbanicity, liberal belief systems, more complete vaccination histories, and parental COVID-19 vaccination history. Higher levels of parental anxiety and lower levels of perceived vaccine danger were associated with increased speed. The severity of the COVID-19 pandemic within one's county was marginally related to speed, but not likelihood. These results underscore the importance of regular assessment of parental intentions across the pandemic, for practitioners to probe parental anxiety levels when discussing vaccination, to explicitly address risk/benefit analyses when communicating with parents, and to target previously routine unvaccinated parents and those in more rural areas to increase vaccine uptake. Comparisons are made with Galanis et al.'s (2022) recent meta-analysis on the topic.}, } @article {pmid38013976, year = {2023}, author = {Garrett, N and Sharot, T}, title = {There is no belief update bias for neutral events: failure to replicate Burton et al. (2022).}, journal = {Journal of cognitive psychology (Hove, England)}, volume = {35}, number = {8}, pages = {876-886}, pmid = {38013976}, issn = {2044-5911}, support = {209108/Z/17/Z/WT_/Wellcome Trust/United Kingdom ; }, abstract = {In a recent paper, Burton et al. claim that individuals update beliefs to a greater extent when learning an event is less likely compared to more likely than expected. Here, we investigate Burton's et al.'s, findings. First, we show how Burton et al.'s data do not in fact support a belief update bias for neutral events. Next, in an attempt to replicate their findings, we collect a new data set employing the original belief update task design, but with neutral events. A belief update bias for neutral events is not observed. Finally, we highlight the statistical errors and confounds in Burton et al.'s design and analysis. This includes mis-specifying a reinforcement learning approach to model the data and failing to follow standard computational model fitting sanity checks such as parameter recovery, model comparison and out of sample prediction. Together, the results find little evidence for biased updating for neutral events.}, } @article {pmid38012710, year = {2023}, author = {Hysong, SJ and Giardina, TD and Freytag, J and SoRelle, R and Murphy, DR and Cully, JA and Sada, YH and Amspoker, AB}, title = {Study protocol: maintaining preventive care during public health emergencies through effective coordination.}, journal = {Implementation science communications}, volume = {4}, number = {1}, pages = {150}, pmid = {38012710}, issn = {2662-2211}, support = {I01 HX003571/HX/HSRD VA/United States ; VA HSR&D SDR 21-248//U.S. Department of Veterans Affairs/ ; }, abstract = {BACKGROUND: Screening lies at the heart of preventive care. However, COVID-19 dramatically disrupted routine screening efforts, resulting in excess mortality not directly attributable to COVID-19. Screening rates during COVID varied markedly by facility and clinical condition, suggesting susceptibilities in screening and referral process workflow. To better understand these susceptibilities and identify new practices to mitigate interrupted care, we propose a qualitative study comparing facilities that exhibited high, low, and highly variable performance (respectively) in screening rates before and during the pandemic. We will be guided by Weaver et al.'s multi-team systems (MTS) model of coordination, using cancer and mental health screening rates as exemplars.

METHOD: Qualitative analysis of interviews and focus groups with primary care personnel, leadership, and patients at 10 VA medical centers. We will select sites based on rurality, COVID-19 caseload at the beginning of the pandemic, and performance on five outpatient clinical performance indicators of cancer and mental health screening. Sites will be categorized into one of five screening performance groups: high performers, low performers, improvers, plummeters, and highly variable. We will create process maps for each performance measure to create a workflow baseline and then interview primary care leadership to update the map at each site. We will clinician conduct focus groups to elicit themes regarding clinician coordination patterns (e.g., handoffs), strategies, and barriers/facilitators to screening during COVID. We will also conduct patient interviews to examine their screening experience during this period, for context. All interviews and focus groups will be audio-recorded, transcribed, and enhanced by field notes. We will analyze clinician transcripts and field notes using iterative, rapid analysis. Patient interviews will be analyzed using inductive/deductive content analysis.

DISCUSSION: Our study represents a unique opportunity to inform the multi-team systems literature by identifying specific forms of information exchange, collective problem solving, and decision-making associated with higher and improved clinical performance. Specifically, our study aims to detect the specific points in the screening and referral process most susceptible to disruption and coordination processes that, if changed, will yield the highest value. Findings apply to future pandemics or any event with the potential to disrupt care.}, } @article {pmid37976670, year = {2024}, author = {van der Schoot, V and van der Meer, E and Hillen, MA and Yntema, HG and Brunner, HG and Oerlemans, AJM}, title = {Exploring uncertainties regarding unsolicited findings in genetic testing.}, journal = {Patient education and counseling}, volume = {119}, number = {}, pages = {108064}, doi = {10.1016/j.pec.2023.108064}, pmid = {37976670}, issn = {1873-5134}, mesh = {Humans ; Uncertainty ; *Genetic Testing ; Genetic Counseling/psychology ; *Counselors/psychology ; Emotions ; }, abstract = {OBJECTIVES: Non-normative uncertainty (uncertainty about empirical facts) and normative uncertainty (uncertainty about moral values or beliefs) regarding unsolicited findings (UFs) might play an important role in clinical genetics. Identifying normative uncertainty is of special interest since it might guide towards novel directions for counseling practice. This study aims to gain insight into the role of non-normative and normative uncertainty regarding UFs, as expressed by counselees and counselors.

METHODS: We performed a secondary qualitative analysis of interviews with counselees (n = 20) and counselors (n = 20) who had been confronted with UFs. Following a deductive approach, we used Han et al.'s existing theoretical framework of uncertainty, in which we additionally incorporated normative uncertainty.

RESULTS: Major issues of non-normative uncertainty were practical and personal for counselees, whilst counselors' uncertainty pertained mainly to scientific issues. Normative uncertainty was a major theme throughout the interviews. We encountered the moral conflicts of autonomy vs. beneficence and non-maleficence and of autonomy vs. truthfulness.

CONCLUSION: Non-normative uncertainty regarding UFs highlights the need to gain more insight in their penetrance and clinical utility. This study suggests moral conflicts are a major source of feelings of uncertainty in clinical genetics.

PRACTICE IMPLICATIONS: Exploring counselees' non-normative uncertainties and normative conflicts seems a prerequisite to optimize genetic counseling.}, } @article {pmid37974182, year = {2023}, author = {Soskolne, CL}, title = {Exposing additional authors who suppress evidence about radiation-induced thyroid cancer in children: a Comment adding to Tsuda et al.'s response to Schüz et al. (2023).}, journal = {Environmental health : a global access science source}, volume = {22}, number = {1}, pages = {79}, pmid = {37974182}, issn = {1476-069X}, mesh = {Adult ; Humans ; Child ; *Thyroid Neoplasms/epidemiology/etiology ; Public Health ; *Fukushima Nuclear Accident ; *Neoplasms, Radiation-Induced/epidemiology ; }, abstract = {BACKGROUND: The need to call out and expose authors for their persistence in improperly using epidemiology has been previously noted. Tsuda et al. have done well to expose Schüz et al.'s arguments/assertions in their recent publication in Environmental Heath. In this Comment, I point out that, also warranting being called out, are the arguments/assertions of Cléro et al. who, in their recent response to an article by Tsuda et al., reiterated the conclusions and recommendations derived from their European project, which were published in Environment International in 2021. Tsuda et al. had critiqued the Cléro et al. 2021 publication in their 2022 review article. However, in their response to it, Cléro et al. deflected by not addressing any of the key points that Tsuda et al. had made in their review regarding the aftermath of the Chernobyl and Fukushima nuclear accidents. In this Comment, I critique Cléro et al.'s inadequate response. Publication of this Comment will help in routing out the improper use of epidemiology in the formulation of public health policy and thereby reduce the influence of misinformation on both science and public policy. My critique of Cléro et al. is not dissimilar from Tsuda et al.'s critique of Schüz et al.: in as much as Schüz et al. should withdraw their work, so should Cléro et al.'s article be retracted.

MAIN BODY: The response by Cléro et al. consists of four paragraphs. First was their assertion that the purpose of the SHAMISEN project was to make recommendations based on scientific evidence and that it was not a systematic review of all related articles. I point out that the Cléro et al. recommendations were not based on objective scientific evidence, but on biased studies. In the second paragraph, Cléro et al. reaffirmed the SHAMISEN Consortium report, which claimed that the overdiagnosis observed in non-exposed adults was applicable to children because children are mirrors of adults. However, the authors of that report withheld statements about secondary examinations in Fukushima that provided evidence against overdiagnosis. In the third paragraph, Cléro et al. provided an explanation regarding their disclosure of conflicting interests, which was contrary to professional norms for transparency and thus was unacceptable. Finally, their insistence that the Tsuda et al. study was an ecological study susceptible to "the ecological fallacy" indicated their lack of epidemiological knowledge about ecological studies. Ironically, many of the papers cited by Cléro et al. regarding overdiagnosis were, in fact, ecological studies.

CONCLUSION: Cléro et al. and the SHAMISEN Consortium should withdraw their recommendation "not to launch a mass thyroid cancer screening after a nuclear accident, but rather to make it available (with appropriate information counselling) to those who request it." Their recommendation is based on biased evidence and would cause confusion regarding public health measures following a nuclear accident. Those authors should, in my assessment, acquaint themselves with modern epidemiology and evidence-based public health. Like Tsuda et al. recommended of Schüz et al., Cléro et al. ought also to retract their article.}, } @article {pmid37953435, year = {2023}, author = {Meyer, GA and Leroux, SJ}, title = {Towards a mechanistic understanding of animal-ecosystem interactions.}, journal = {The Journal of animal ecology}, volume = {92}, number = {12}, pages = {2244-2247}, doi = {10.1111/1365-2656.14023}, pmid = {37953435}, issn = {1365-2656}, support = {#RGPIN-2020-04132//Natural Sciences and Engineering Research Council of Canada/ ; }, mesh = {Animals ; *Ecosystem ; *Forests ; Biomass ; Plants/microbiology ; Soil ; Soil Microbiology ; Nitrogen ; Carbon ; Mammals ; }, abstract = {Research Highlight: Ferraro, K. M., Welker, L., Ward, E. B., Schmitz, O. J., & Bradford, M. A. (2023). Plant mycorrhizal associations mediate the zoogeochemical effects of calving subsidies by a forest ungulate. Journal of Animal Ecology, https://doi.org/10.1111/1365-2656.14002. Animals play large roles in ecosystem elemental cycling but predicting effects in diverse contexts remains a substantial challenge. Fundamental to progress is (1) identifying mechanisms by which animals impact nutrient distribution and cycling, and (2) disentangling how environmental context mediates the operation of alternative mechanisms. In an elegant field experiment, Ferraro et al. (2023) provide the first detailed exploration of the impact of nutrient inputs from mammalian parturition on soil functioning and the stoichiometry of plant tissues. The authors find that nitrogen from experimental additions of ungulate parturition material (natal fluids) is rapidly incorporated into microsite soil organic pools and plant tissues. They also find that soil processes (soil microbial biomass, rates of carbon mineralization, nitrogen mineralization and nitrification) and the nitrogen content of plant tissues above- and belowground are increased by addition of parturition material. Notably, the authors identify that increases in some soil processes and plant tissue nitrogen are weaker in microsites dominated by ericoid mycorrhizal plants than those dominated by ectomycorrhizal plants. These findings demonstrate that parturition depositions, a ubiquitous but overlooked mechanism of mammalian impacts on ecosystems, impact ecosystem processes and plant tissue stoichiometry. Furthermore, plant-fungal associations are a predictive axis of context dependency mediating zoogeochemical effects at fine scales. Ferraro et al.'s (2023) novel approach simultaneously advances mechanistic understanding of animal-ecosystem interactions at fine scales and facilitates prediction of ungulate effects on nutrient availability at landscape extents.}, } @article {pmid37949785, year = {2023}, author = {Camviel, N and Akkari, L}, title = {Uniting innate and adaptive immunity in glioblastoma; an α-CTLA-4 quest.}, journal = {Trends in immunology}, volume = {44}, number = {12}, pages = {933-935}, doi = {10.1016/j.it.2023.10.011}, pmid = {37949785}, issn = {1471-4981}, mesh = {Humans ; Mice ; Animals ; CTLA-4 Antigen ; *Glioblastoma ; Adaptive Immunity ; Antibodies ; Immunotherapy ; Immunity, Innate ; }, abstract = {Immunotherapies have thus far led to disappointing outcomes in patients suffering from glioblastoma. Published in Immunity, Chen et al.'s recent study shows the therapeutic potential of an αCTLA-4 antibody (Ab), specifically in murine mesenchymal-like glioblastoma. αCTLA-4 Ab efficacy relied on the distinctive cooperation between CD4[+] Th1 T cells and microglia, unleashing a potent antitumor response.}, } @article {pmid37947875, year = {2024}, author = {Azaad, S and Sebanz, N}, title = {Potential benefits of synchronous action observation and motor imagery: a commentary on Eaves et al. 2022.}, journal = {Psychological research}, volume = {88}, number = {6}, pages = {1908-1910}, pmid = {37947875}, issn = {1430-2772}, mesh = {Humans ; *Imagination/physiology ; *Psychomotor Performance/physiology ; Motor Activity/physiology ; }, abstract = {In a recent Psychological Research article, Eaves et al. (2022) review the literature on how motor imagery (MI) practice combined with action observation (AO) enhances motor performance. The authors propose that the synchronous form of AO and MI (AOMI) affords unique benefits to performance that are not possible when the two interventions are performed asynchronously. We discuss three questions raised by Eaves et al.'s review: (1) are there any clear advantages to synchronous AOMI? (2) Are there super-additive benefits to AOMI, and if so, are they unique to synchronous AOMI? (3) How might coordinative AOMI, in which people imagine complementary actions, facilitate joint actions?}, } @article {pmid37942709, year = {2023}, author = {Furuya, S and Liu, J and Sun, Z and Lu, Q and Fletcher, JM}, title = {The Big (Genetic) Sort? A Research Note on Migration Patterns and Their Genetic Imprint in the United Kingdom.}, journal = {Demography}, volume = {60}, number = {6}, pages = {1649-1664}, doi = {10.1215/00703370-11054960}, pmid = {37942709}, issn = {1533-7790}, mesh = {Humans ; United Kingdom ; *Transients and Migrants ; Educational Status ; }, abstract = {This research note reinvestigates Abdellaoui et al.'s (2019) findings that genetically selective migration may lead to persistent and accumulating socioeconomic and health inequalities between types (coal mining or non-coal mining) of places in the United Kingdom. Their migration measure classified migrants who moved to the same type of place (coal mining to coal mining or non-coal mining to non-coal mining) into "stay" categories, preventing them from distinguishing migrants from nonmigrants. We reinvestigate the question of genetically selective migration by examining migration patterns between places rather than place types and find genetic selectivity in whether people migrate and where. For example, we find evidence of positive selection: people with genetic variants correlated with better education moved from non-coal mining to coal mining places with our measure of migration. Such findings were obscured in earlier work that could not distinguish nonmigrants from migrants.}, } @article {pmid37939113, year = {2024}, author = {Wang, Z and Liu, YL and Chen, Y and Siegel, L and Cappelleri, JC and Chu, H}, title = {Double-Negative Results Matter: A Reevaluation of Sensitivities for Detecting SARS-CoV-2 Infection Using Saliva Versus Nasopharyngeal Swabs.}, journal = {American journal of epidemiology}, volume = {193}, number = {3}, pages = {548-560}, pmid = {37939113}, issn = {1476-6256}, support = {R01 LM012982/LM/NLM NIH HHS/United States ; UL1 TR002494/TR/NCATS NIH HHS/United States ; }, mesh = {Humans ; *COVID-19/diagnosis ; SARS-CoV-2 ; Negative Results ; Saliva ; Nasopharynx ; }, abstract = {In a recent systematic review, Bastos et al. (Ann Intern Med. 2021;174(4):501-510) compared the sensitivities of saliva sampling and nasopharyngeal swabs in the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection by assuming a composite reference standard defined as positive if either test is positive and negative if both tests are negative (double negative). Even under a perfect specificity assumption, this approach ignores the double-negative results and risks overestimating the sensitivities due to residual misclassification. In this article, we first illustrate the impact of double-negative results in the estimation of the sensitivities in a single study, and then propose a 2-step latent class meta-analysis method for reevaluating both sensitivities using the same published data set as that used in Bastos et al. by properly including the observed double-negative results. We also conduct extensive simulation studies to compare the performance of the proposed method with Bastos et al.'s method for varied levels of prevalence and between-study heterogeneity. The results demonstrate that the sensitivities are overestimated noticeably using Bastos et al.'s method, and the proposed method provides a more accurate evaluation with nearly no bias and close-to-nominal coverage probability. In conclusion, double-negative results can significantly impact the estimated sensitivities when a gold standard is absent, and thus they should be properly incorporated.}, } @article {pmid37936131, year = {2023}, author = {Lv, C and Yang, L and Ngan, P and Xiao, W and Zhao, T and Tang, B and Chen, X and He, H}, title = {Role of the tonsil-oropharynx ratio on lateral cephalograms in assessing tonsillar hypertrophy in children seeking orthodontic treatment.}, journal = {BMC oral health}, volume = {23}, number = {1}, pages = {836}, pmid = {37936131}, issn = {1472-6831}, mesh = {Male ; Female ; Child ; Humans ; Child, Preschool ; *Palatine Tonsil/diagnostic imaging ; Cross-Sectional Studies ; *Oropharynx/diagnostic imaging ; Radiography ; Hypertrophy ; }, abstract = {OBJECTIVES: To analyze the diagnostic value of the tonsil-oropharynx (T/O) ratio on lateral cephalograms for evaluating tonsillar hypertrophy (TH).

METHODS: A cross-sectional study was performed on 185 consecutive children (101 males, 84 females; mean age 7.3 ± 1.4 years) seeking orthodontic treatment. The T/O ratios on lateral cephalograms were calculated following Baroni et al.'s method. Tonsil sizes were clinically determined according to the Brodsky grading scale. Spearman correlation coefficients between the T/O ratio and clinical tonsil size were calculated with the total sample and subgroups and then compared between subgroups. Diagnostic value was analyzed using the receiver operating characteristic (ROC) curve, sensitivity, specificity, positive and negative predictive values, and accuracy.

RESULTS: There was a strong correlation between the T/O ratio and clinical tonsil size in children (ρ = 0.73; P < 0.001). A significantly higher correlation coefficient was found in the Class III children. The ROC curve revealed an area under the curve of 0.90 (95% CI, 0.86-0.94; P < 0.001). The optimal cutoff value of the T/O ratio for predicting TH was 0.58, with a sensitivity of 98.7% and specificity of 64.2%. Employing the cutoff value of 0.5, the sensitivity was 100% and the specificity was 45.9%.

CONCLUSIONS: Measurement of the T/O ratio on lateral cephalograms may be helpful to initial screening in children for TH. Practitioners may combine the clinical examination of tonsil size with the cephalometric findings for a more comprehensive evaluation.}, } @article {pmid37929915, year = {2023}, author = {Ganta, PK and Teja, MR and Chang, CJ and Sambandam, A and Kamaraj, R and Chu, YT and Ding, S and Chen, HY and Chen, HY}, title = {Improvement of catalytic activity of aluminum complexes for the ring-opening polymerization of ε-caprolactone: aluminum thioamidate and thioureidate systems.}, journal = {Dalton transactions (Cambridge, England : 2003)}, volume = {52}, number = {46}, pages = {17132-17147}, doi = {10.1039/d3dt03198e}, pmid = {37929915}, issn = {1477-9234}, abstract = {In this study, a series of Al complexes bearing amidates, thioamidates, ureidates, and thioureidates were synthesized and their catalytic activity for ε-caprolactone (CL) polymerization was evaluated. SPr-Al exhibited a higher catalytic activity than OPr-Al (3.2 times as high for CL polymerization; [CL] : [SPr-Al] : [BnOH] = 100 : 0.5 : 2; [SPr-Al] = 10 mM, conv. = 93% after 14 min at 25 °C), and USCl-Al exhibited a higher catalytic activity than UCl-Al (4.6 times as high for CL polymerization; [CL] : [USCl-Al] : [BnOH] = 100 : 0.5 : 2; [USCl-Al] = 10 mM, conv. = 90% after 15 min at 25 °C). Regardless of whether aluminum amidates or ureidates were present, thioligands improved the polymerization rate of aluminum catalysts. Density functional theory calculations revealed that the eight-membered ring [SPr-AlOMe2]2 decomposed into the four-membered ring SPr-AlOMe2. However, [OPr-AlOMe2]2 did not decompose because of its strong bridging Al-O bond. The overall activation energy required for CL polymerization was lower when using [SPr-AlOMe2]2 (18.1 kcal mol[-1]) as a catalyst than when using [OPr-AlOMe2]2 (23.9 kcal mol[-1]). This is because the TS2a transition state of SPr-AlOMe2 had a more open coordination geometry with a small N-Al-S angle (72.91°) than did TS3c of [OPr-AlOMe2]2, the crowded highest-energy transition state of [OPr-AlOMe2]2 with a larger N-Al-O angle (99.63°).}, } @article {pmid37929319, year = {2024}, author = {Hofmann, MJ and Mokros, A and Schneider, S}, title = {The joy of being frightened: Fear experience in psychopathy.}, journal = {Journal of personality}, volume = {92}, number = {2}, pages = {321-341}, doi = {10.1111/jopy.12890}, pmid = {37929319}, issn = {1467-6494}, mesh = {Humans ; *Fear/physiology ; *Happiness ; Antisocial Personality Disorder ; Pleasure ; }, abstract = {OBJECTIVE: Psychopathic traits are associated with abnormalities in fear processing. While traditional theories focus on a lack of fear, Hosker-Field et al. (2016) provided a new perspective. They suggested that individuals with elevated psychopathic traits may experience threatening situations with appreciation or positivity, resulting in reduced negative fear responses and heightened positive responses (fear enjoyment hypothesis, FEH).

METHOD: Our study aimed to refine Hosker-Field et al.'s (2016) study design, addressing methodological limitations and improving the inconsistent operationalization of fear experience in the literature. In an online sample of 353 participants from the general population, we examined the relationship between the FEH and relevant psychopathic traits, specifically those derived from the PCL-R framework (i.e., SRP 4 Factor 1), and from a more trait-based approach to psychopathy with assumed links to fearlessness (i.e., TriPM Boldness).

RESULTS: By employing linear mixed effect models, we extended Hosker-Field et al.'s correlational analysis and provided further evidence for the FEH, particularly in relation to psychopathic traits measured using the PCL-R framework. The results regarding Boldness, however, are somewhat inconclusive.

CONCLUSION: The present study enhances existing research on fear deficits in psychopathy by assessing the subjective experience of individuals facing threat.}, } @article {pmid37920911, year = {2024}, author = {Greenfield, TK}, title = {Debating Shield et al.'s perspectives on how to formulate alcohol drinking guidelines.}, journal = {Addiction (Abingdon, England)}, volume = {119}, number = {1}, pages = {22-23}, doi = {10.1111/add.16375}, pmid = {37920911}, issn = {1360-0443}, support = {P50 AA005595/AA/NIAAA NIH HHS/United States ; P50 AA005595/AA/NIAAA NIH HHS/United States ; }, mesh = {Humans ; *Alcohol Drinking ; }, } @article {pmid37919859, year = {2024}, author = {Evans, SC and Shaughnessy, S}, title = {Emotion regulation as central to psychopathology across childhood and adolescence: a commentary on Nobakht et al. (2023).}, journal = {Journal of child psychology and psychiatry, and allied disciplines}, volume = {65}, number = {3}, pages = {354-357}, doi = {10.1111/jcpp.13910}, pmid = {37919859}, issn = {1469-7610}, mesh = {Humans ; Adolescent ; Child ; Cohort Studies ; *Emotional Regulation/physiology ; Psychopathology ; Irritable Mood/physiology ; *Mental Disorders/etiology ; Attention Deficit and Disruptive Behavior Disorders ; }, abstract = {An important goal of clinical/developmental research is to identify factors contributing to the onset and maintenance of psychopathology - particularly factors that could be modified through intervention. Large-scale, multi-informant, longitudinal studies provide valuable opportunities for testing such etiological hypotheses, as illustrated by Nobakht et al.'s recent six-wave cohort study spanning ages 4-14. At a within-person level, emotion regulation (ER) deficits consistently predicted oppositional defiant disorder (ODD) symptoms (including both irritability and defiance), whereas victimization did not. These results comport with growing evidence highlighting ER's centrality to ODD and psychopathology more broadly. While the ER findings carry promising implications, caution is warranted in interpreting the results for victimization given that its association with psychopathology is well-documented. More research is needed to test precise questions about within- and between-person processes involving ER, victimization, and psychopathology across development. Pressing research questions include whether, how, and when youths' ER can be modified, and with what effects on clinical outcomes.}, } @article {pmid37916181, year = {2023}, author = {Liu, K and Chen, CY and Wang, LS and Jo, H and Kung, CC}, title = {Is increased activation in the fusiform face area to Greebles a result of appropriate expertise training or caused by Greebles' face likeness?.}, journal = {Frontiers in neuroscience}, volume = {17}, number = {}, pages = {1224721}, pmid = {37916181}, issn = {1662-4548}, abstract = {BACKGROUND: In 2011, Brants et al. trained eight individuals to become Greeble experts and found neuronal inversion effects [NIEs; i.e., higher fusiform face area (FFA) activity for upright, rather than inverted Greebles]. These effects were also found for faces, both before and after training. By claiming to have replicated the seminal Greeble training study by Gauthier and colleagues in 1999, Brants et al. interpreted these results as participants viewing Greebles as faces throughout training, contrary to the original argument of subjects becoming Greeble experts only after training. However, Brants et al.'s claim presents two issues. First, their behavioral training results did not replicate those of Gauthier and Tarr conducted in 1997 and 1998, raising concerns of whether the right training regime had been adopted. Second, both a literature review and meta-analysis of NIEs in the FFA suggest its impotency as an index of the face(-like) processing.

OBJECTIVES: To empirically evaluate these issues, the present study compared two documented training paradigms Gauthier and colleagues in 1997 and 1998, and compared their impact on the brain.

METHODS: Sixteen NCKU undergraduate and graduate students (nine girls) were recruited. Sixty Greeble exemplars were categorized by two genders, five families, and six individual levels. The participants were randomly divided into two groups (one for Greeble classification at all three levels and the other for gender- and individual-level training). Several fMRI tasks were administered at various time points, specifically, before training (1st), during training (2nd), and typically no <24 h after reaching expertise criterion (3rd).

RESULTS: The ROI analysis results showed significant increases in the FFA for Greebles, and a clear neural "adaptation," both only in the Gauthier97 group and only after training, reflecting clear modulation of extensive experiences following an "appropriate" training regime. In both groups, no clear NIEs for faces nor Greebles were found, which was also in line with the review of extant studies bearing this comparison.

CONCLUSION: Collectively, these results invalidate the assumptions behind Brants et al.'s findings.}, } @article {pmid37914100, year = {2024}, author = {Chu, WM and Ho, HE and Wei, JC}, title = {Comment on Cheng et al.'s "Risk factors for poor COVID-19 outcomes in patients with psychiatric disorders".}, journal = {Brain, behavior, and immunity}, volume = {115}, number = {}, pages = {333-334}, doi = {10.1016/j.bbi.2023.10.028}, pmid = {37914100}, issn = {1090-2139}, mesh = {Humans ; *COVID-19 ; *Mental Disorders/complications/psychology ; Risk Factors ; }, } @article {pmid37903574, year = {2023}, author = {Laurenzi, C and Operario, D and Mutambo, C and Mupakile, E and Banda, B and Ngakongwa, F and Kilonzo, R and Busakhwe, C and Ronan, A and Toska, E}, title = {Lessons From Implementing Ask-Boost-Connect-Discuss, a Peer-Delivered Psychosocial Intervention for Young Mothers Living With HIV in Malawi, Tanzania, Uganda, and Zambia.}, journal = {Global health, science and practice}, volume = {11}, number = {5}, pages = {}, pmid = {37903574}, issn = {2169-575X}, support = {K43 TW011434/TW/FIC NIH HHS/United States ; P30 AI050409/AI/NIAID NIH HHS/United States ; R25 MH067127/MH/NIMH NIH HHS/United States ; }, mesh = {Pregnancy ; Adolescent ; Humans ; Female ; Zambia ; Malawi ; Uganda ; Tanzania ; *Psychosocial Intervention ; *HIV Infections/therapy ; }, abstract = {Adolescent girls and young women in sub-Saharan Africa are at high risk of HIV, unintended pregnancy, and early motherhood. These intersecting risks can adversely affect their developmental trajectories and lifelong well-being. Because young mothers living with HIV in these settings experience high levels of stigma, shame, and isolation, tailored psychosocial intervention approaches for this group are critical yet unavailable. Enlisting young peer supporters may be a promising way to expand the reach of health services and enhance psychosocial well-being. To date, few peer-based interventions have targeted young mothers living with HIV. In 2019-2021, we codeveloped a peer-based, facility-embedded intervention package, Ask-Boost-Connect-Discuss (ABCD), with young peer supporters to address the psychosocial needs of young mothers living with HIV in Malawi, Tanzania, Uganda, and Zambia. We then analyzed programmatic data from ABCD to assess the feasibility of using young peers to deliver psychosocial support. Data sources included post-intervention interviews, focus groups, and written feedback from multiple stakeholders (participants, peer supporters, their supervisors, and clinic-based mentors), which were analyzed thematically. We organized our findings according to Bowen et al.'s feasibility framework. Findings spoke to the acceptability, practicality, and integration of the ABCD program. We found that young peer supporters were seen as acceptable program implementers; able to adopt responsive, engaging, and nonjudgmental approaches; and supported through training, technical skills development, and supervision, alongside purposeful facility integration. Importantly, we also found evidence reflecting the roles of demand and adaptation in program delivery (i.e., how peers responded to emerging participant needs or pivoted in their approach based on shifting circumstances). We conclude that considerations of intervention feasibility and/or program fidelity should be attuned to the dynamic qualities of young peer supporters as implementers and should extend beyond standard modes of assessment to consider intervention codevelopment and implementation as an iterative and adaptive process.}, } @article {pmid37902132, year = {2024}, author = {Anderson, H and Scantlebury, A and Galdas, P and Adamson, J}, title = {The well-being of nurses working in general practice during the COVID-19 pandemic: A qualitative study (The GenCo Study).}, journal = {Journal of advanced nursing}, volume = {80}, number = {4}, pages = {1574-1591}, doi = {10.1111/jan.15919}, pmid = {37902132}, issn = {1365-2648}, support = {N/A//General Nursing Council for England and Wales Trust/ ; }, mesh = {Humans ; *COVID-19/epidemiology ; Pandemics ; Quality of Health Care ; *General Practice ; Qualitative Research ; *Nurses ; }, abstract = {AIM: Exploration of experiences of nurses working in general practice during the COVID-19 pandemic to evaluate the impact on nurses' professional well-being.

DESIGN: An exploratory qualitative study comprised of case studies of three general practice sites in England and a nationwide interview study of nurses working in general practice and nurse leaders. The study was funded by The General Nursing Council for England and Wales Trust. University of York ethics approval (HSRGC/2021/458/I) and Health Research Authority approval was obtained (IRAS: 30353, Protocol number: R23982, Ref 21/HRA/5132, CPMS: 51834).

METHODS: Forty participants took part. Case site data consisted of interviews/focus groups and national data consisted of semi-structured interviews. Data collection took place between April and August 2022. Analysis was underpinned by West et al.'s The courage of compassion. Supporting nurses and midwives to deliver high-quality care, The King's fund, 2020 ABC framework of nurses' core work well-being needs.

FINDINGS: The majority of participants experienced challenges to their professional well-being contributed to by lack of recognition, feeling undervalued and lack of involvement in higher-level decision-making. Some participants displayed burnout and stress. Structural and cultural issues contributed to this and many experiences pre-dated, but were exacerbated by, the COVID-19 pandemic.

CONCLUSIONS: By mapping findings to the ABC framework, we highlight the impact of the COVID-19 pandemic on the well-being of nurses working in general practice and contributing workplace factors. The issues identified have implications for retention and for the future of nursing in general practice. The study highlights how this professional group can be supported in the future.

IMPACT: The study contributes to our understanding of the experiences of nurses working in general practice during the COVID-19 pandemic and beyond. Findings have implications for this skilled and experienced workforce, for retention of nurses in general practice, the sustainability of the profession more broadly and care quality and patient safety.

REPORTING METHOD: Standards for Reporting Qualitative Research (O'Brien et al. in Journal of the Association of American Medical Colleges, 89(9), 1245-1251, 2014).

As this was a workforce study there was no patient or public contribution.}, } @article {pmid37898804, year = {2023}, author = {Mensah, ABB and Nunoo, H and Mensah, KB and Okyere, J and Dzomeku, VM and Apiribu, F and Asoogo, C and Clegg-Lamptey, JN}, title = {Impact of childhood and adolescence cancer on family caregivers: a qualitative analysis of strains, resources and coping behaviours.}, journal = {BMC psychology}, volume = {11}, number = {1}, pages = {361}, pmid = {37898804}, issn = {2050-7283}, mesh = {Child ; Humans ; Adolescent ; *Caregivers/psychology ; Stress, Psychological/psychology ; Quality of Life ; Adaptation, Psychological ; *Neoplasms/therapy ; Qualitative Research ; Family ; }, abstract = {BACKGROUND: The physical demands of caring for children and adolescents diagnosed with cancer, over a lengthy period, exert significant strain on the health and well-being of family caregivers. The capacity of family caregivers to surmount and cope with the various strains they experience due to the diagnosis and treatment trajectory is essential to the quality of life of the child and adolescent who has been diagnosed with cancer. However, the experiences of family caregivers have been under-explored. This study explored the strains, resources, and coping strategies of family caregivers of children and adolescents diagnosed with cancer in Ghana.

METHODS: Guided by a descriptive phenomenological design, 20 semi-structured interviews with family caregivers were conducted at a tertiary health facility that provides paediatric oncology services. The study was conducted between June and October 2022. The interviews were transcribed verbatim, translated and coded using NVivo software. An inductive thematic analysis approach using Vaismoradi et al.'s thematic analysis framework was followed in analysing the data.

RESULTS: The study revealed that family caregivers of children diagnosed with cancer experienced three main strains: somatic strains (poor sleep quality, loss of appetite, and unintended weight loss), economic strains (financial burden and loss of economic livelihood), and psychosocial strains (isolation from social activities and network, frustration and helplessness, and balancing multiple family needs). The following themes emerged as coping resources: family cohesiveness, community support, and support from health care providers. Coping strategies that emerged included trusting in God and being self-motivated.

CONCLUSION: The study concludes that family caregivers experience somatic, economic, and psychosocial strains. However, they can leverage available resources (family cohesiveness, community support, and support from healthcare providers) to cope with these strains. There is a need to educate and sensitize family caregivers about the potential strains that they are likely to experience prior to the assumption of care roles. Also, the formal inclusion of non-governmental organizations and religious bodies will ensure that family caregivers receive sufficient community support to cope with the strains of caregiving.}, } @article {pmid37893789, year = {2023}, author = {Lyon, TR and Galbraith, A}, title = {Mindful Self-Compassion as an Antidote to Burnout for Mental Health Practitioners.}, journal = {Healthcare (Basel, Switzerland)}, volume = {11}, number = {20}, pages = {}, pmid = {37893789}, issn = {2227-9032}, abstract = {The objective of this correlational study was to explore the relationship between levels of self-compassion and burnout for currently practicing mental health practitioners (MHPs) in the United States. All professionals are vulnerable to burnout based on various types of organizational stressors, but burnout is of particular concern for health care service providers who may need to adopt a stance of detachment, or emotional distance, as relief from intense workloads, with clients. The data were collected through an online survey. Regression analysis found that scores from Neff's Self-Compassion Scale were a significant negative predictor of levels of MHP burnout, as assessed by Schaufeli et al.'s Burnout Assessment Tool, p < 0.001. The implication of this finding is that cultivating self-compassion appears to be a pragmatic self-care strategy for MHPs to mitigate the negative effects of burnout. More educational and occupational training in self-compassion practices as self-care should be provided to help protect the physical and emotional well-being of MHPs. The deleterious systemic effects of burnout make MHP self-care an ethical issue, along with the need to identify protective factors, prevention, and treatment of burnout.}, } @article {pmid37891613, year = {2023}, author = {Cao, Y and Kong, X and Yang, D and Li, J}, title = {Precise placement of a triple-cavity drainage tube by guide wire exchange method for esophagojejunal anastomotic fistula after gastrectomy.}, journal = {World journal of surgical oncology}, volume = {21}, number = {1}, pages = {344}, pmid = {37891613}, issn = {1477-7819}, mesh = {Humans ; *Drainage/methods ; *Fistula/surgery ; Anastomosis, Surgical/adverse effects ; Gastrectomy/adverse effects ; Abscess/therapy ; Anastomotic Leak/surgery ; Retrospective Studies ; }, abstract = {This is a letter to the editor on a study by Ding et al. on the role of the three-tube method via precise interventional placement for esophagojejunal anastomotic fistula after gastrectomy. They suggest using transnasal insertion of abscess drainage catheter, jejunal decompression tube, and jejunal nutrition tube under fluoroscopy as a simple, minimally invasive, effective, and safe method for treating esophagojejunal anastomotic fistula. Compared to Ding et al.'s method, we presented a new procedure for the esophagojejunal anastomotic fistula. In this procedure, we precisely place a homemade triple-cavity drainage tube by guide wire exchange method near the esophagojejunal anastomotic fistula for continuous irrigation and negative pressure suction, which can provide adequate drainage and result in fistula's self-healing. This procedure can also be performed at bedside without any anesthesia; therefore, it is a more simple, minimally invasive, effective, and safe treatment for esophagojejunal anastomotic fistula.}, } @article {pmid37888422, year = {2023}, author = {Zhao, W and Xu, M and Xu, C and Li, B and Hu, X and Yang, C and Luo, L}, title = {Judgments of Learning Following Retrieval Practice Produce Minimal Reactivity Effect on Learning of Education-Related Materials.}, journal = {Journal of Intelligence}, volume = {11}, number = {10}, pages = {}, pmid = {37888422}, issn = {2079-3200}, support = {32000742//National Natural Science Foundation of China/ ; 32171045//National Natural Science Foundation of China/ ; 32200841//National Natural Science Foundation of China/ ; 2022-01-132-BZK01//Research Program Funds of the Collaborative Innovation Center of Assessment toward Basic Education Quality at Beijing Normal University/ ; }, abstract = {Testing (i.e., retrieval practice) is one of the most powerful strategies to boost learning. A recent study observed an incidental finding that making judgments of learning (JOLs) following retrieval practice further enhanced learning of education-related texts to a medium extent (Cohen's d = 0.44) by comparison with retrieval practice itself, suggesting that making JOLs may serve as an easy-to-implement educational intervention to improve the benefits of testing. Three experiments (one pre-registered) were conducted to test the replicability of Ariel et al.'s incidental finding and to further determine whether making JOLs following retrieval practice reactively enhances the benefits of testing for text learning. The three experiments consistently provided Bayesian evidence supporting no reactivity effect of JOLs following retrieval practice, regardless of whether the replication experiments were conducted in a laboratory (Experiment 1) or online (Experiments 2 and 3), whether the stimuli were presented in the same language (Experiments 2 and 3) or not (Experiment 1), and whether participants were recruited from the sample pool (Experiment 2) or not (Experiments 1 and 3) as in the original study. These null findings imply that making JOLs cannot be utilized as a practical strategy to enhance the benefits of testing for learning of educationally related materials. Possible explanations for the null reactivity effect of JOLs following retrieval practice are discussed.}, } @article {pmid37878155, year = {2024}, author = {Mingolo, S and Prpic, V and Mariconda, A and Brugger, P and Drack, T and Bilotta, E and Agostini, T and Murgia, M}, title = {It's SNARC o' clock: manipulating the salience of the context in a conceptual replication of Bächtold et al.'s (1998) clockface study.}, journal = {Psychological research}, volume = {88}, number = {3}, pages = {837-851}, pmid = {37878155}, issn = {1430-2772}, mesh = {Humans ; Reaction Time/physiology ; *Space Perception/physiology ; *Judgment/physiology ; Memory, Short-Term ; }, abstract = {The Spatial-Numerical Association of Response Codes (SNARC) effect consists in faster left-/right-key responses to small/large numbers. (Bächtold et al., Neuropsychologia 36:731-735, 1998) reported the reversal of this effect after eliciting the context of a clockface-where small numbers are represented on the right and large numbers on the left. The present study investigates how the salience of a particular spatial-numerical context, which reflects the level of activation of the context in working memory, can alter Spatial Numerical Associations (SNAs). Four experiments presented the clockface as context and gradually increased its salience using different tasks. In the first two experiments (low salience), the context was presented at the beginning of the experiment and its retrieval was not required to perform the tasks (i.e., random number generation in Experiment 1, magnitude classification and parity judgement in Experiment 2). Results revealed regular left-to-right SNAs, unaffected by the context. In Experiment 3 (medium salience), participants performed magnitude classification and parity judgement (primary task), and a Go/No-go (secondary task) which required the retrieval of the context. Neither the SNARC effect nor a reversed-SNARC emerged, suggesting that performance was affected by the context. Finally, in Experiment 4 (high salience), the primary task required participants to classify numbers based on their position on the clockface. Results revealed a reversed SNARC, as in (Bächtold et al., Neuropsychologia 36:731-735, 1998). In conclusion, SNARC is disrupted when the context is retrieved in a secondary task, but its reversal is observed only when the context is relevant for the primary task.}, } @article {pmid37872408, year = {2023}, author = {Xu, L and Zhang, G and Zhang, D and Zhang, J and Zhang, X and Bai, X and Chen, L and Peng, Q and Xiao, Y and Wang, H and Jin, Z and Sun, H}, title = {An MRI-based grading system for preoperative risk estimation of positive surgical margin after radical prostatectomy.}, journal = {Insights into imaging}, volume = {14}, number = {1}, pages = {178}, pmid = {37872408}, issn = {1869-4101}, support = {2022-PUMCH-A-033//National High Level Hospital Clinical Research Funding/ ; 2022-PUMCH-A-035//National High Level Hospital Clinical Research Funding/ ; 2022-PUMCH-B-069//National High Level Hospital Clinical Research Funding/ ; 2022-I2M-C&T-B-019//CAMS Innovation Fund for Medical Sciences (CIFMS)/ ; }, abstract = {OBJECTIVE: To construct a simplified grading system based on MRI features to predict positive surgical margin (PSM) after radical prostatectomy (RP).

METHODS: Patients who had undergone prostate MRI followed by RP between January 2017 and January 2021 were retrospectively enrolled as the derivation group, and those between February 2021 and November 2022 were enrolled as the validation group. One radiologist evaluated tumor-related MRI features, including the capsule contact length (CCL) of lesions, frank extraprostatic extension (EPE), apex abutting, etc. Binary logistic regression and decision tree analysis were used to select risk features for PSM. The area under the curve (AUC), sensitivity, and specificity of different systems were calculated. The interreader agreement of the scoring systems was evaluated using the kappa statistic.

RESULTS: There were 29.8% (42/141) and 36.4% (32/88) of patients who had PSM in the derivation and validation cohorts, respectively. The first grading system was proposed (mrPSM1) using two imaging features, namely, CCL ≥ 20 mm and apex abutting, and then updated by adding frank EPE (mrPSM2). In the derivation group, the AUC was 0.705 for mrPSM1 and 0.713 for mrPSM2. In the validation group, our grading systems showed comparable AUC with Park et al.'s model (0.672-0.686 vs. 0.646, p > 0.05) and significantly higher specificity (0.732-0.750 vs. 0.411, p < 0.001). The kappa value was 0.764 for mrPSM1 and 0.776 for mrPSM2. Decision curve analysis showed a higher net benefit for mrPSM2.

CONCLUSION: The proposed grading systems based on MRI could benefit the risk stratification of PSM and are easily interpretable.

CRITICAL RELEVANCE STATEMENT: The proposed mrPSM grading systems for preoperative prediction of surgical margin status after radical prostatectomy are simplified compared to a previous model and show high specificity for identifying the risk of positive surgical margin, which might benefit the management of prostate cancer.

KEY POINTS: • CCL ≥ 20 mm, apex abutting, and EPE were important MRI features for PSM. • Our proposed MRI-based grading systems showed the possibility to predict PSM with high specificity. • The MRI-based grading systems might facilitate a structured risk evaluation of PSM.}, } @article {pmid37871962, year = {2023}, author = {Lei, F and Chen, WT and Brecht, ML and Zhang, ZF and Hu, Y and Xu, T and Wang, S and Lee, E}, title = {Cross-Cultural Adaptation of Lung Cancer Screening Health Belief Scale in Chinese Americans: A Methodological Study.}, journal = {Journal of nursing measurement}, volume = {31}, number = {4}, pages = {489-501}, doi = {10.1891/JNM-2021-0093}, pmid = {37871962}, issn = {1945-7049}, mesh = {Humans ; *Cross-Cultural Comparison ; Early Detection of Cancer ; *Lung Neoplasms/diagnosis ; Psychometrics ; Reproducibility of Results ; Surveys and Questionnaires ; Asian ; }, abstract = {Background and Purpose: The purpose of this study is to report the process of adapting the existing Lung Cancer Screening Health Belief Scale to be used in Chinese Americans. Methods: Guided by Flaherty et al.'s cross-cultural equivalency model, the methodology used in the adaptation process consists of four steps, including preliminary modification after a comprehensive literature review, forward and backward translation, expert review, and cognitive interviews among participants. Results: The modified culturally fitted Lung Cancer Screening Health Belief Scale included 57 items and 6 subscales, which proved highly reliable and valid through the expert review and participants' review. Conclusions: This study provided an example for a novice cross-cultural researcher to adapt an instrument to be used in another population with a different language. Further research is needed to work out a standard guideline for cross-cultural instrument adaptation.}, } @article {pmid37870612, year = {2024}, author = {Çelik, N and Ünsal, G and Taştanoğlu, H}, title = {Predictive markers of metabolically healthy obesity in children and adolescents: can AST/ALT ratio serve as a simple and reliable diagnostic indicator?.}, journal = {European journal of pediatrics}, volume = {183}, number = {1}, pages = {243-251}, pmid = {37870612}, issn = {1432-1076}, mesh = {Humans ; Child ; Adolescent ; *Obesity, Metabolically Benign/diagnosis/epidemiology ; *Pediatric Obesity/diagnosis/epidemiology ; Risk Factors ; ROC Curve ; Waist Circumference ; Body Mass Index ; *Metabolic Syndrome/diagnosis/epidemiology ; Phenotype ; }, abstract = {UNLABELLED: This study aimed to estimate the prevalence of metabolically healthy obesity (MHO) according to two different consensus-based criteria and to investigate simple, measurable predictive markers for the diagnosis of MHO. Five hundred and ninety-three obese children and adolescents aged 6-18 years were included in the study. The frequency of MHO was calculated. ROC analysis was used to estimate the predictive value of AST/ALT ratio, waist/hip ratio, MPV, TSH, and Ft4 cut-off value for the diagnosis of MHO. The prevalence of MHO was 21.9% and 10.2% according to 2018 and 2023 consensus-based MHO criteria, respectively. AST/ALT ratio cut-off value for the diagnosis of MHO was calculated as ≥ 1 with 77% sensitivity and 52% specificity using Damanhoury et al.'s criteria (AUC = 0.61, p = 0.02), and 90% sensitivity and 51% specificity using Abiri et al.'s criteria (AUC = 0.70, p = 0.01). Additionally, using binomial regression analysis, only the AST/ALT ratio is independently and significantly associated with the diagnosis of MHO (p = 0.03 for 2018 criteria and p = 0.04 for 2023 criteria).

CONCLUSION: The ALT/AST ratio may be a useful indicator of MHO in children and adolescents.

WHAT IS KNOWN: • Metabolically healthy obesity refers to people who are obese but do not have any of the standard cardio-metabolic risk factors. • Metabolically healthy obesity is not entirely harmless; the metabolic characteristics of individuals with this phenotype are less favorable than those of healthy lean groups. Moreover, it is not a constant state, and there may be a transition to metabolically unhealthy phenotypes over time.

WHAT IS NEW: • The prevalence of MHO is 21.9% and 10.2% according to 2018 and 2023 consensus-based metabolically healthy obesity criteria, respectively. • The ALT/AST ratio may be a useful indicator of metabolically healthy obesity in children and adolescents.}, } @article {pmid37868461, year = {2023}, author = {Sammoud, K and Mahdi, Z and Benzaida, K and Elrhaffouli, Y and Yamlahi, M and Gourinda, A and Charif, F and Bousgheiri, F and Elbouri, H and Adil, N}, title = {Cross-Cultural Adaptation of Mediterranean Diet Adherence Screener (MEDAS) Into Moroccan Arabic to Measure the Degree of Mediterranean Diet Adherence.}, journal = {Cureus}, volume = {15}, number = {9}, pages = {e45556}, pmid = {37868461}, issn = {2168-8184}, abstract = {Background The Mediterranean diet (MD) has been recognized by several studies as beneficial for health improvement. The degree of adherence to this diet has also been evaluated using several scales, particularly time-consuming measures such as the Food Frequency Questionnaire (FFQ). This study aims to (a) adapt into Moroccan Arabic the 14-item Mediterranean Diet Adherence Screener (MEDAS), which is a simple and brief tool that assesses the degree of diet adherence and was used in the Prevencion con Dieta Mediterranea (PREDIMED) study, and (b) determine its psychometric properties. Methods MEDAS consists of 12 questions on food frequency and two on dietary habits, with each question scoring 0 or 1. To translate and adapt the scale, Beaton et al.'s six-step cross-cultural adaptation process guidelines were followed. The screener's psychometric properties were tested on staff at the CHU Mohammed VI (Tangier), i.e., the hospital's administrative and maintenance staff, excluding medical and paramedical personnel. Internal consistency was evaluated using the Kuder-Richardson 21 (K-R 21) formula, while test-retest reliability was assessed using the intraclass correlation coefficient (ICC). Moreover, criterion validity was performed using the Spearman correlation between the MEDAS and the MedQ-Sus scores. Discrimination performance was also tested using the receiving operating characteristic (ROC) curve. Results The validation study included 160 participants who completed both questionnaires. The K-R 21 formula estimated strong internal consistency in the range of 0.851. The ICC of test-retest reliability was significant at 0.876 95% CI [0.831-0.909]. The MEDAS score correlated significantly with the comparative MedQ-Sus score (Spearman's rho = 0.494 95% CI [0.363-0.606], p < 0.001). Also, MEDAS can strongly distinguish between MD adherence and non-adherence (optimal cut-off = 7.5, sensitivity 0.81, specificity = 0.57), with an area under the curve (AUC) value of 0.743 95% CI [0.667-0.819], p < 0.001. Conclusion The results showed that MEDAS is a valid and time-saving instrument for assessing adherence to the MD in the Moroccan population.}, } @article {pmid37865708, year = {2023}, author = {Inoue, Y and Burriss, RP and Hasegawa, T and Kiyonari, T}, title = {Testosterone promotes dominance behaviors in the Ultimatum Game after players' status increases.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {18029}, pmid = {37865708}, issn = {2045-2322}, mesh = {Humans ; *Testosterone/analysis ; *Competitive Behavior ; Social Dominance ; Saliva/chemistry ; Cross-Sectional Studies ; Hydrocortisone/analysis ; }, abstract = {Although testosterone is generally considered to promote dominance behaviors, in humans it fosters behaviors appropriate to achieving and maintaining social status, contingent upon the situation. Recent cross-sectional studies, such as Inoue et al. (Sci Rep 7:5335, 2017), have shown that dominance behaviors induced by testosterone are modulated by high status. Yet, it remains ambiguous whether a rise in social status within real-world social groups reshapes the relationship between testosterone and dominance behavior. To investigate this longitudinal question, we added a second wave to Inoue et al.'s study, collecting further data after an interval of 2 years. Members of a university rugby team that adheres to a rigid hierarchical order rooted in seniority played the Ultimatum Game with teammates and provided saliva for assays of testosterone and cortisol. Our analysis reveals that individuals with higher baseline salivary testosterone levels exhibited more dominance as their position in the hierarchy increased according to their seniority.}, } @article {pmid37858387, year = {2023}, author = {Alpert, E and Sloan, DM and Lee, DJ and Cole, TA and Shotwell Tabke, C}, title = {Response to Sonis's (2023) commentary on Alpert et al.'s (2023) systematic review of mediators and mechanisms of PTSD treatments.}, journal = {Clinical psychology review}, volume = {106}, number = {}, pages = {102338}, doi = {10.1016/j.cpr.2023.102338}, pmid = {37858387}, issn = {1873-7811}, mesh = {Humans ; *Stress Disorders, Post-Traumatic/therapy ; Systematic Reviews as Topic ; }, } @article {pmid37837871, year = {2023}, author = {Nakamori, M and Shimizu, Y and Takahashi, T and Toko, M and Yamada, H and Hayashi, Y and Ushio, K and Yoshikawa, K and Hiraoka, A and Yoshikawa, M and Nagasaki, T and Mikami, Y and Maruyama, H}, title = {Swallowing sound index analysis using electronic stethoscope and artificial intelligence for patients with Parkinson's disease.}, journal = {Journal of the neurological sciences}, volume = {454}, number = {}, pages = {120831}, doi = {10.1016/j.jns.2023.120831}, pmid = {37837871}, issn = {1878-5883}, mesh = {Humans ; Deglutition/physiology ; *Parkinson Disease/diagnosis/diagnostic imaging ; *Deglutition Disorders/diagnostic imaging/etiology ; Artificial Intelligence ; *Stethoscopes ; Electronics ; }, abstract = {BACKGROUND AND PURPOSE: Several noninvasive tools assess swallowing disorders, including electronic stethoscope artificial intelligence (AI) analysis for remote diagnosis, with the potential for telemedicine. This study investigated the swallowing sound index in patients with Parkinson's disease (PD).

METHODS: This single-arm, open-label trial assessed the impact of cervical percutaneous interferential current stimulation on swallowing in patients with PD classified as Hoehn-Yahr stages 2-4. Stimulation was conducted for 8 weeks. Baseline data were used to examine the link between the swallowing sound index and indicators such as videofluoroscopy (VF). Furthermore, we examined changes in the swallowing sound index after the intervention.

RESULTS: Twenty-five patients were included. The swallowing sound index in patients with PD was higher than that in those with amyotrophic lateral sclerosis but considerably lower than that in healthy controls. The number of patients with normal EAT-10 scores positively correlated with the swallowing sound index, whereas elevated C-reactive protein levels were negatively correlated with the swallowing sound index. However, the index displayed no correlation with other indicators, including the VF results. Despite the intervention, the index remained unchanged throughout the study.

CONCLUSION: In patients with PD, a decrease in the swallowing sound index suggests a potential association between swallowing disorders and the risk of aspiration pneumonia.

TRIAL REGISTRATION NUMBER: jRCTs062220013.}, } @article {pmid37831653, year = {2023}, author = {Mairson, TM}, title = {Patient Autonomy: How a Student's Surgical Experience Highlights the Need for a New Standard Operating Procedure.}, journal = {The Journal of clinical ethics}, volume = {34}, number = {3}, pages = {285-287}, doi = {10.1086/726814}, pmid = {37831653}, issn = {1046-7890}, mesh = {Humans ; *Informed Consent ; *Students ; }, abstract = {AbstractThe concerns regarding patient autonomy presented in August A. Culbert et al.'s "Navigating Informed Consent and Patient Safety in Surgery: Lessons for Medical Students and Junior Trainees" fall just short of addressing the main issue. Patient autonomy is not something that just one member of a team should consider, and it should not be something that any protocol should have the power to subvert, particularly in an environment as tenuous as the operating room. This article will take the concerns regarding the ethics of removing a patient's hearing aid prior to entering the operating room presented in the aforementioned article and show the necessity for a new standard operating procedure.}, } @article {pmid37831645, year = {2023}, author = {Kwak, CB}, title = {Practical Ethics: A Medical Student's Ethical Case in Surgery Clerkship.}, journal = {The Journal of clinical ethics}, volume = {34}, number = {3}, pages = {282-284}, doi = {10.1086/726810}, pmid = {37831645}, issn = {1046-7890}, mesh = {Humans ; *Students, Medical ; Curriculum ; *Clinical Clerkship ; Informed Consent ; Ethics, Medical ; }, abstract = {AbstractOne factor that impedes medical students from speaking up about ethical situations is the lack of sufficient knowledge and skills in conflict resolution. This may also affect students' decision and timing to intervene. This article will provide practical ways to effectively and efficiently address the medical student's ethical case presented in August A. Culbert et al.'s "Navigating Informed Consent and Patient Safety in Surgery: Lessons for Medical Students and Junior Trainees."}, } @article {pmid37821653, year = {2023}, author = {Hjerppe, J and Shahramian, K and Rosqvist, E and Lassila, LVJ and Peltonen, J and Närhi, TO}, title = {Gastric acid challenge of lithium disilicate-reinforced glass-ceramics and zirconia-reinforced lithium silicate glass-ceramic after polishing and glazing-impact on surface properties.}, journal = {Clinical oral investigations}, volume = {27}, number = {11}, pages = {6865-6877}, pmid = {37821653}, issn = {1436-3771}, mesh = {Humans ; *Lithium ; *Gastric Acid ; Materials Testing ; Computer-Aided Design ; Dental Porcelain/chemistry ; Ceramics/chemistry ; Zirconium/chemistry ; Silicates ; Surface Properties ; }, abstract = {OBJECTIVES: To investigate the impact of simulated gastric acid on the surface properties of lithium disilicate-reinforced glass-ceramics and zirconia-reinforced lithium silicate glass-ceramic after certain polishing and glazing procedures.

MATERIALS AND METHODS: Four different types of square-shaped specimens (10 × 10 × 2 mm[3], n = 13) were manufactured: lithium disilicate-reinforced glass-ceramic milled and polished (LDS-P); milled, polished, and glazed (LDS-PG); milled, glazed, and no polishing (LDS-G); and milled and polished zirconia-reinforced lithium silicate glass-ceramic (ZR-LS). Specimens were immersed in hydrochloride acid (HCl 0.06 M, pH 1.2) to simulate gastric acid irritation and stored in the acid for 96 h in 37 °C. Specimen weight, surface gloss, Vickers surface microhardness and surface roughness (Ra, Rq, with optical profilometer), and surface roughness on nanometer level (Sq, Sal, Sq/Sal, Sdr, Sds with atomic force microscope) were measured before and after the acid immersion.

RESULTS: ZR-LS specimens lost significantly more weight after acid immersion (p = 0.001), also surface microhardness of ZR-LS was significantly reduced (p = 0.001). LDS-G and LDS-PG showed significantly lower surface roughness (Sa, Sq) values compared to LDS-P before (p ≤ 0.99) and after (p ≤ 0.99) acid immersion and ZR-LS after acid immersion (p ≤ 0.99).

CONCLUSIONS: Gastric acid challenge affects the surface properties of lithium disilicate-reinforced glass-ceramic and zirconia-reinforced lithium silicate glass-ceramic. Glazing layer provides lower surface roughness, and the glazed surface tends to smoothen after the gastric acid challenge.

CLINICAL RELEVANCE: Surface finish of lithium disilicate-reinforced glass-ceramic and zirconia-reinforced lithium silicate glass-ceramic has a clear impact on material's surface properties. Gastric acidic challenge changes surface properties but glazing seems to function as a protective barrier. Nevertheless, also glazing tends to smoothen after heavy gastric acid challenge. Glazing can be highly recommended to all glass-ceramic restorations but especially in patients with gastroesophageal reflux disease (GERD) and eating disorders like bulimia nervosa.}, } @article {pmid37806668, year = {2023}, author = {Marchand, GJ and Masoud, A}, title = {Response to Dr. Somovilla del Saz's letter to the editor regarding "Risk of all-cause and cardiac-related mortality after vaccination against COVID-19: A meta-analysis of self-controlled case series studies".}, journal = {Human vaccines & immunotherapeutics}, volume = {19}, number = {3}, pages = {2264599}, pmid = {37806668}, issn = {2164-554X}, abstract = {This is a response to Dr. Somovilla del Saz's letter to the editor regarding Marchand et al.'s article, "Risk of all-cause and cardiac-related mortality after vaccination against COVID-19: A meta-analysis of self-controlled case series studies." The response is on behalf of all authors clarifying misconceptions about the work.}, } @article {pmid37793343, year = {2023}, author = {Wu, G and Zhao, N and Zhao, L}, title = {Microbial-host isozyme: A novel target in "drug the bug" strategies for diabetes.}, journal = {Cell metabolism}, volume = {35}, number = {10}, pages = {1677-1679}, doi = {10.1016/j.cmet.2023.09.008}, pmid = {37793343}, issn = {1932-7420}, mesh = {Humans ; Isoenzymes/metabolism ; *Diabetes Mellitus/drug therapy ; *Gastrointestinal Microbiome/physiology ; *Metabolic Diseases ; Bacteria/metabolism ; }, abstract = {The role of the gut microbiome in metabolic diseases, such as diabetes, has emerged as a pivotal area of medical research. Wang et al.'s recent work reported that a gut bacteria-derived microbial-host isozyme, mimicking a human enzyme responsible for blood glucose regulation, can significantly impact the efficacy of diabetes medications.}, } @article {pmid37789555, year = {2023}, author = {Weinstein, NY and Baldwin, DA}, title = {The many faces of moralized self-control: Puritanical morality is not reducible to cooperation concerns.}, journal = {The Behavioral and brain sciences}, volume = {46}, number = {}, pages = {e320}, doi = {10.1017/S0140525X23000419}, pmid = {37789555}, issn = {1469-1825}, mesh = {Humans ; *Morals ; *Judgment ; }, abstract = {Fitouchi et al.'s moral disciplining approach highlights the significant role social evaluations of self-control appear to play in human moral judgment. At the same time, attributing the wide range of puritanical concerns to a singular focus on self-control seems unwarranted. A more pluralistic approach would enrich understanding of moral judgment in all its cultural and historical diversity.}, } @article {pmid37789546, year = {2023}, author = {Starmans, C}, title = {Little puritans?.}, journal = {The Behavioral and brain sciences}, volume = {46}, number = {}, pages = {e314}, doi = {10.1017/S0140525X23000328}, pmid = {37789546}, issn = {1469-1825}, mesh = {Child ; Adult ; Humans ; Child, Preschool ; *Morals ; }, abstract = {I propose that young children may be a useful test case for Fitouchi et al.'s theory that certain seemingly harmless acts are moralized because they are seen as risk factors for future poor cooperation. The theory predicts that prior to the development of certain folk-psychological beliefs about self-control, children should be untroubled by violations of puritanical morality, and that an adult-like folk psychology of self-control should develop in tandem with disapproval of such violations.}, } @article {pmid37789536, year = {2023}, author = {Becker, D and Bernecker, K}, title = {Don't throw the baby out with the bathwater: Indulging in harmless pleasures can support self-regulation and foster cooperation.}, journal = {The Behavioral and brain sciences}, volume = {46}, number = {}, pages = {e295}, doi = {10.1017/S0140525X23000456}, pmid = {37789536}, issn = {1469-1825}, mesh = {Humans ; *Pleasure ; *Self-Control ; }, abstract = {In this commentary we challenge Fitouchi et al.'s puritanical morality account by presenting evidence showing (1) that pursuing harmless pleasures can actually support self-regulation, and (2) that sharing pleasurable experiences can foster cooperation. We conclude that puritanical morality is not as adaptive as presented, and may even suppress the potential benefits pleasure can have for the individual and society.}, } @article {pmid37789525, year = {2023}, author = {Kollareth, D and Russell, JA}, title = {Purity is not a distinct moral domain.}, journal = {The Behavioral and brain sciences}, volume = {46}, number = {}, pages = {e308}, doi = {10.1017/S0140525X23000365}, pmid = {37789525}, issn = {1469-1825}, mesh = {Humans ; *Emotions ; Morals ; *Disgust ; Judgment ; Intention ; }, abstract = {Purity violations overlap with other moral domains. They are not uniquely characterized by hypothesized markers of purity - the witness's emotion of disgust, taint to perpetrator's soul, or the diminished role of intention in moral judgment. Thus, Fitouchi et al.'s proposition that puritanical morality (a subset of violations in the purity domain) is part of cooperation-based morality is an important advance.}, } @article {pmid37787470, year = {2024}, author = {Parshina, O and Zdorova, N and Kuperman, V}, title = {Cross-linguistic comparison in reading sentences of uniform length: Visual-perceptual demands override readers' experience.}, journal = {Quarterly journal of experimental psychology (2006)}, volume = {77}, number = {8}, pages = {1694-1702}, doi = {10.1177/17470218231206719}, pmid = {37787470}, issn = {1747-0226}, mesh = {Humans ; *Reading ; *Saccades/physiology ; Female ; Adult ; Male ; Young Adult ; Visual Perception/physiology ; Psycholinguistics ; Pattern Recognition, Visual/physiology ; Linguistics ; Fixation, Ocular/physiology ; Language ; }, abstract = {Accurate saccadic targeting is critical for efficient reading and is driven by the sensory input under the eye-gaze. Yet whether a reader's experience with the distributional properties of their written language also influences saccadic targeting is an open debate. This study of Russian sentence reading follows Cutter et al.'s (2017) study in English and presents readers with sentences consisting of words of the same length. We hypothesised that if the readers' experience matters as per discrete control account, Russian readers would produce longer saccades and farther landing positions than the ones produced by English readers. On the contrary, if the saccadic targeting is primarily driven by the immediate perceptual demands that override readers' experience as per the dynamic adjustment account, the saccades of Russian and English readers would be of the same length, resulting in similar landing positions. The results in both Cutter et al. and the present study provided evidence for the latter account: Russian readers showed rapid and accurate adjustment of saccade lengths and landing positions to the highly constrained input. Crucially, the saccade lengths and landing positions did not differ between English and Russian readers even in the cross-linguistically length-matched stimuli.}, } @article {pmid37786971, year = {2023}, author = {Javdani, S and Larsen, SE and Allen, NE and Blackburn, AM and Griffin, B and Rieger, A}, title = {Mixed methods in community psychology: A values-forward synthesis.}, journal = {American journal of community psychology}, volume = {72}, number = {3-4}, pages = {355-365}, pmid = {37786971}, issn = {1573-2770}, support = {L40 MH108089/MH/NIMH NIH HHS/United States ; }, mesh = {Humans ; *Research Design ; *Psychology ; }, abstract = {Mixed methods research (MMR) combines multiple traditions, methods, and worldviews to enrich research design and interpretation of data. In this virtual special issue, we highlight the use of MMR within the field of community psychology. The first MMR studies appeared in flagship community psychology journals over 30 years ago (in 1991). To explore the uses of MMR in the field, we first review existing literature by identifying all papers appearing in either Journal of Community Psychology or American Journal of Community Psychology in which the word "mixed" appeared. A total of 88 publications were identified. Many of these papers illustrate the pragmatic use of MMR to evaluate programs and to answer different research questions using different methods. We coded articles based on Green et al.'s classifications of the purpose of the mixing: triangulation, development, complementarity, expansion, and initiation. Complementarity was the most frequently used purpose (46.6% of articles), and nearly a quarter of articles mixed for multiple purposes (23.86%). We also coded for any community psychology values advanced by the use of mixed methods. We outline three themes here with corresponding exemplars. These articles illustrate how MMR can highlight ecological analysis and reconsider dominant, individual-level paradigms; center participant and community member experiences; and unpack paradoxes to increase the usefulness of research findings.}, } @article {pmid37781486, year = {2023}, author = {Nartker, M and Firestone, C and Egeth, H and Phillips, I}, title = {Six ways of failing to see (and why the differences matter).}, journal = {i-Perception}, volume = {14}, number = {5}, pages = {20416695231198762}, pmid = {37781486}, issn = {2041-6695}, abstract = {Sometimes we look but fail to see: our car keys on a cluttered desk, a repeated word in a carefully proofread email, or a motorcycle at an intersection. Wolfe and colleagues present a unifying, mechanistic framework for understanding these "Looked But Failed to See" errors, explaining how such misses arise from natural constraints on human visual processing. Here, we offer a conceptual taxonomy of six distinct ways we might be said to fail to see, and explore: how these relate to processes in Wolfe et al.'s model; how they can be distinguished experimentally; and, why the differences matter.}, } @article {pmid37777802, year = {2023}, author = {Baba, A and Richards, DP and Smith, M and Pallone, N and Vanderhout, S and Prebeg, M and Elsman, EBM and Potter, BK and Offringa, M and Butcher, NJ}, title = {Youth and family involvement in the development of a plain language trial results communication tool: CommuniKIDS.}, journal = {Research involvement and engagement}, volume = {9}, number = {1}, pages = {88}, pmid = {37777802}, issn = {2056-7529}, support = {MYG-171684/CAPMC/CIHR/Canada ; }, abstract = {BACKGROUND: Pediatric trials are possible through voluntary participation of children, youth (age ≤ 18 years), and their families. Despite important arguments for trialists to provide trial progress or results, and evidence that participants desire it, this information remains rarely shared with youth and their families. Little guidance exists on how trialists can best communicate trial results back to participants and their families. Guided by Liabo et al.'s framework, we describe how we developed a pediatric-specific, "plain language summary" clinical trial results template called CommuniKIDS with an adult patient partner, family partner (parent), youth advisors, and parent advisors, taking into account their unique knowledge needs and preferences.

MAIN TEXT: Patient and Public Involvement (PPI) was integrated in the development of the CommuniKIDS template. In collaboration with Clinical Trials Ontario, we used a generic trial results template as a starting point. The core project leadership team included a patient partner and a family partner from project inception to completion. Five youth (ages 13-18 years) and eight parent advisors were consulted at each point of the development process through three virtual workshops conducted separately; youth workshops were led by a youth facilitator. During these workshops, advisors agreed on the importance and value of sharing trial results, and expressed their preferences on content, format, and timing of sharing trial results. PPI-led improvements included the addition of three new sections to the CommuniKIDS template: "at a glance," "side effects," and "next steps." We reflect on our PPI strategy in the context of five "values" and six "practicalities" identified as good PPI principles, and summarize lessons learned when collaborating with youth and families from this project.

CONCLUSION: Involvement of a patient partner, a family partner, youth advisors, and parent advisors in the development of CommuniKIDS was critical to create a clinical trial results template that is useful and relevant to its end-users. To our knowledge, CommuniKIDS is the first to meaningfully engage youth and parents as advisors and partners in developing a plain language summary results template for pediatric trial participants and their families. Our experience of co-developing CommuniKIDS demonstrates that meaningful PPI can be achieved in trial results communication and knowledge translation practices. This report provides resources for those seeking to involve youth and families in their initiatives and in meaningfully sharing trial results.}, } @article {pmid37775032, year = {2023}, author = {Desmedt, O and Corneille, O and Luminet, O and Maurage, P and Vögele, C and Schulz, A}, title = {Do Schulz et al.'s (2021) findings support the validity of the heartbeat counting task? Joint conclusion to commentaries.}, journal = {Biological psychology}, volume = {184}, number = {}, pages = {108694}, doi = {10.1016/j.biopsycho.2023.108694}, pmid = {37775032}, issn = {1873-6246}, mesh = {Humans ; Heart Rate ; *Interoception ; }, } @article {pmid37769938, year = {2023}, author = {Schulz, A and Vögele, C}, title = {Why Desmedt et al.'s commentary does not apply to the findings of Schulz et al. (2021) concerning the validity of the heartbeat counting task.}, journal = {Biological psychology}, volume = {184}, number = {}, pages = {108689}, doi = {10.1016/j.biopsycho.2023.108689}, pmid = {37769938}, issn = {1873-6246}, mesh = {Humans ; Heart Rate ; *Interoception ; Awareness ; }, } @article {pmid37766622, year = {2023}, author = {Grüning, DJ}, title = {Advanced testing of the LoT hypothesis by social reasoning.}, journal = {The Behavioral and brain sciences}, volume = {46}, number = {}, pages = {e276}, doi = {10.1017/S0140525X2300184X}, pmid = {37766622}, issn = {1469-1825}, mesh = {Humans ; *Language ; *Problem Solving ; }, abstract = {I elaborate on Quilty-Dunn et al.'s integration of the language-of-thought hypothesis in social reasoning by outlining two discrepancies between the experimental paradigms referred to by the authors and the social world: Self-referential projection and deliberate thinking in experiments. Robust tests of the hypothesis in social reasoning should include observational, natural, and cross-cultural approaches.}, } @article {pmid37766621, year = {2023}, author = {Cesana-Arlotti, N}, title = {The reemergence of the language-of-thought hypothesis: Consequences for the development of the logic of thought.}, journal = {The Behavioral and brain sciences}, volume = {46}, number = {}, pages = {e268}, doi = {10.1017/S0140525X23001802}, pmid = {37766621}, issn = {1469-1825}, mesh = {Humans ; *Cognition ; *Logic ; Language ; Cognitive Science ; }, abstract = {Quilty-Dunn et al. defended the reemergence of language-of-thought hypothesis (LoTH). My commentary builds up implications for the study of the development of our logical capacities. Empirical support for logically augmented LoT systems calls for the investigation of their logical primitives and developmental origin. Furthermore, Quilty-Dunn et al.'s characterization of LoT helps the quest for the foundation of logic by dissociating logical cognition from natural language.}, } @article {pmid37766618, year = {2023}, author = {Kibbe, MM}, title = {The language-of-thought as a working hypothesis for developmental cognitive science.}, journal = {The Behavioral and brain sciences}, volume = {46}, number = {}, pages = {e280}, doi = {10.1017/S0140525X23002030}, pmid = {37766618}, issn = {1469-1825}, abstract = {A science of prelinguistic infant cognition must take seriously the language-of-thought (LoT) hypothesis. I show how the LoT framework enables us to identify the representational and computational capacities of infant minds and the developmental factors that act on these capacities, and explain how Quilty-Dunn et al.'s take on LoT has important upshots for developmental theory-building.}, } @article {pmid37766613, year = {2023}, author = {Attah, NO and Machery, E}, title = {Is evidence of language-like properties evidence of a language-of-thought architecture?.}, journal = {The Behavioral and brain sciences}, volume = {46}, number = {}, pages = {e264}, doi = {10.1017/S0140525X23001875}, pmid = {37766613}, issn = {1469-1825}, mesh = {Humans ; *Language ; *Cognitive Science ; }, abstract = {We argue that Quilty-Dunn et al.'s commitment to representational pluralism undermines their case for the language-of-thought hypothesis as the evidence they present is consistent with the operation of the other representational formats that they are willing to accept.}, } @article {pmid37766604, year = {2023}, author = {Hafri, A and Green, EJ and Firestone, C}, title = {Compositionality in visual perception.}, journal = {The Behavioral and brain sciences}, volume = {46}, number = {}, pages = {e277}, doi = {10.1017/S0140525X23001838}, pmid = {37766604}, issn = {1469-1825}, mesh = {Humans ; *Visual Perception ; *Language ; }, abstract = {Quilty-Dunn et al.'s wide-ranging defense of the Language of Thought Hypothesis (LoTH) argues that vision traffics in abstract, structured representational formats. We agree: Vision, like language, is compositional - just as words compose into phrases, many visual representations contain discrete constituents that combine in systematic ways. Here, we amass evidence extending this proposal, and explore its implications for how vision interfaces with the rest of the mind.}, } @article {pmid37755550, year = {2024}, author = {Ortega, E and Bryan, CYX and Christine, NSC}, title = {The Pulse of Singapore: Short-Term HRV Norms.}, journal = {Applied psychophysiology and biofeedback}, volume = {49}, number = {1}, pages = {55-61}, pmid = {37755550}, issn = {1573-3270}, support = {RGRF 20 CAR20//National Council for Social Services, Singapore & Ngee Ann Kongsi, Singapore/ ; }, mesh = {Humans ; Male ; Female ; Singapore ; Adult ; *Heart Rate/physiology ; Adolescent ; Middle Aged ; Young Adult ; Aged ; Child ; Aged, 80 and over ; *Autonomic Nervous System/physiology ; Reference Values ; Age Factors ; Sex Factors ; }, abstract = {Short-term heart rate variability (HRV) is increasingly used to assess autonomic nervous system activity and found to be useful for monitoring and providing care due to its quick measurement. With evidence of low HRV associated with chronic diseases, mental disorders, and an increased risk of cardiovascular disease, having normative data of HRV across the age spectrum would be useful for monitoring health and well-being of a population. This study examines HRV of healthy Singapore sample, with ages ranging from 10 to 89 years. Short-term HRV of five minutes was measured from 2,143 participants. 974 males and 1,169 females, and overall HRV was found to be 42.4ms (RMSSD) and 52.0 ms (SDNN) with a further breakdown of HRV by age and gender. Overall HRV declined with age and gender, although gender differences dissipated in the 60s age range onwards, with the 50s age range having the sharpest decline in HRV. Short-term HRV norms were similar to Nunan et al.'s (2010) systematic review in various populations and less similar to Choi et al.'s (2020) study on Koreans.}, } @article {pmid37747484, year = {2023}, author = {van Baal, ST and Hohwy, J and Verdejo-García, A and Konstantinidis, E and Walasek, L}, title = {Fenneman et al.'s (2022) review of formal impulsivity models: Implications for theory and measures of impulsivity.}, journal = {Psychological bulletin}, volume = {149}, number = {11-12}, pages = {746-756}, doi = {10.1037/bul0000404}, pmid = {37747484}, issn = {1939-1455}, support = {//Monash-Warwick Alliance Accelerator Fund/ ; }, abstract = {In Fenneman et al.'s (2022) review of theories and integrated impulsivity model, the authors distinguish between information impulsivity (i.e., acting without considering consequences) and temporal impulsivity (i.e., the tendency to pick sooner outcomes over later ones). The authors find that both types of impulsivity can be adaptive in different contexts. For example, when individuals experience scarcity of resources or when they are close to a minimum level of reserves (critical threshold). In this commentary, we extend their findings to a discussion about the measurement of impulsivity. We argue that a common method for measuring temporal impulsivity in which people make decisions between outcomes that are spaced out in time (intertemporal choice tasks), puts individuals in a specific context that is unlikely to generalize well to other situations. Furthermore, trait measures of impulsivity may only be modestly informative about future impulsive behavior because they largely abstract away from important context. To address these issues, we advocate for the development of dynamic measures of the two types of impulsivity. We argue that measuring temporal impulsivity in naturalistic contexts with varying environmental and state parameters could provide insights into whether individuals (i.e., humans and nonhuman animals) react to environmental changes adaptively, while trait measures of impulsivity more generally should collect and provide more contextual information. Dynamic measurement of different types of impulsivity will also allow for more discussion about adaptive impulsive responses in different contexts, which could help combat the stigmatization of various disorders associated with impulsivity. (PsycInfo Database Record (c) 2025 APA, all rights reserved).}, } @article {pmid37744641, year = {2023}, author = {Yi, S and Kanetkar, V and Brauer, P}, title = {Campus food service users' support for nudge strategies for fruit and vegetable-rich items: findings from a large Canadian national sample.}, journal = {Journal of nutritional science}, volume = {12}, number = {}, pages = {e93}, pmid = {37744641}, issn = {2048-6790}, mesh = {Humans ; Canada ; *Fruit ; Vegetables ; *Food Services ; Health Facilities ; }, abstract = {Although customer support is critical to the wider uptake of nudging strategies to promote fruits and vegetables (FV) in institutional food service (FS) settings, empirical research is sparse and typically based on small convenience samples. An online survey was conducted to assess support, perceived effectiveness and intrusiveness of nine nudge types drawn from Münscher et al.'s Taxonomy of Choice Architecture. We focused on the setting of campus FSs across Canada. A national sample of post-secondary students regularly using campus FSs was used (N 1057). Support for changing the range of options (B3) was the highest, closely followed by changing option-related effort (B2) and changing option-related consequences (B4). Facilitating commitment (C2), changing default (B1) and providing a social reference point (A3) received lowest support. Furthermore, we extracted three clusters of respondents based on perceived effectiveness and intrusiveness of nudge types. Characterised by a relatively low level of perceived effectiveness and moderately high level of intrusiveness, Cluster 1 (61⋅7 % of the sample) reported the lowest support for nudges. Cluster 2 (26⋅6 %), characterised by intermediate effectiveness and low intrusiveness of nudging, reported a high level of support for nudges. Lastly, Cluster 3 (11⋅7 %), characterised by high perceived effectiveness of as well as high perceived intrusiveness, reported the highest level of support for nudges. Findings confirm overall support for FV nudging, with significant differences across nudge types. Differences in customers' acceptance and perception across nudge types offer campus FS operators initial priors in selecting nudges to promote FV.}, } @article {pmid37743917, year = {2023}, author = {Ghasemisedaghat, S and Eslamian, G and Kazemi, SN and Rashidkhani, B and Taheripanah, R}, title = {Association of fertility diet score with endometriosis: a case-control study.}, journal = {Frontiers in nutrition}, volume = {10}, number = {}, pages = {1222018}, pmid = {37743917}, issn = {2296-861X}, abstract = {BACKGROUND AND AIMS: Different factors, such as environmental, epigenetic, genetic and immunological, have been identified as potential risks for developing endometriosis. However, the correlation between dietary patterns and endometriosis is currently unknown. The aim of this study was to explore the potential link between fertility diet score and the odds of endometriosis.

METHODS: This study was a hospital-based case-control study that took place in a gynecology clinic in Tehran, Iran, between February 2021 and January 2022. A total of 107 newly diagnosed endometriosis cases and 210 controls were included. The participants' habitual diets were evaluated using a food frequency questionnaire, and their fertility diet score was estimated using a point system based on Chavarro et al.'s criteria. The logistic regression was utilized to calculate the odds ratios (OR) with 95% confidence intervals (CIs).

RESULTS: The study found that women who adherence to fertility diet have a lower odds of endometriosis. This was observed in both the base model and the adjusted model, with a significant decrease in odds of endometriosis by 66% (OR = 0.44, 95%CI = 0.27-0.71, p = 0.001) and 54% (aOR = 0.46, 95%CI = 0.23-0.90, p = 0.022), respectively. Additionally, consuming vegetable proteins and multivitamins were also associated with lower odds of endometriosis. On the other hand, consuming animal proteins, heme iron, and having a high glycemic load were associated with significantly higher odds of endometriosis.

CONCLUSION: Our research supports the hypothesis that following a fertility diet may decrease the odds of endometriosis in Iranian women. However, these findings should be verified through extensive, prospective studies.}, } @article {pmid37741176, year = {2024}, author = {He, H and Jian, X and Zen, T and Feng, B and Hu, Y and Yuan, Z and Zhao, Z and Gao, X and Lv, L and Cao, Z}, title = {Sulfur defect induced Cd0.3Zn0.7S in-situ anchoring on metal organic framework for enhanced photothermal catalytic CO2 reduction to prepare proportionally adjustable syngas.}, journal = {Journal of colloid and interface science}, volume = {653}, number = {Pt A}, pages = {687-696}, doi = {10.1016/j.jcis.2023.09.103}, pmid = {37741176}, issn = {1095-7103}, abstract = {The rapid recombination of interfacial charges is considered to be the main obstacle limiting the photocatalytic CO2 reduction. Thus, it is a challenge to research an accurate and stable charge transfer control strategy. MIL-53 (Al)-S/Cd0.3Zn0.7S (MAS/CZS-0.3) photocatalysts with chemically bonded interfaces were constructed by in-situ electrostatic assembly of sulfur defect Cd0.3Zn0.7S (CZS-0.3) on the surface of MIL-53 (Al) (MAW), which enhanced interfacial coupling and accelerated electron transfer efficiency. An adjustable proportion of syngas (H2/CO) was prepared by photothermal catalytic CO2 reduction at micro-interface. and the optimal yield of CO (66.10 μmol∙g[-1]∙h[-1]) and H2 (71.0 μmol∙g[-1]∙h[-1]) was realized by the MAS/CZS-0.3 photocatalyst. The improved activity was due to the photogenerated electrons migrated from CZS-0.3 to the adsorption active sites of MAS, which strengthened the adsorption and activation of CO2 on MAS. The photothermal catalytic CO2 reduction to CO follows the pathway of CO2→*COOH → CO and CO2→*HCO3[-]→CO. This work provided a reference for the research, characterization, and application of in-situ anchoring of metal organic frameworks in photothermal catalytic CO2 reduction, and provided a green path for the supply of Syngas in industry.}, } @article {pmid37734696, year = {2024}, author = {Kumar, N and Rauf, SA and Rajendar, R and Arbab, S}, title = {Cost-Effectiveness Analysis of Sacubitril/Valsartan for Reducing the Use of Implantable Cardioverter-Defibrillator (ICD) and the Risk of Death in ICD-Eligible Heart Failure Patients With Reduced Ejection Fraction.}, journal = {Current problems in cardiology}, volume = {49}, number = {1 Pt B}, pages = {102093}, doi = {10.1016/j.cpcardiol.2023.102093}, pmid = {37734696}, issn = {1535-6280}, mesh = {Humans ; Stroke Volume ; Cost-Effectiveness Analysis ; *Defibrillators, Implantable ; Tetrazoles/therapeutic use ; Valsartan ; *Heart Failure/therapy ; *Ventricular Dysfunction, Left/chemically induced ; }, abstract = {This critical review of Kaddoura et al.'s article on sacubitril/valsartan in heart failure patients underscores the importance of considering potential adverse effects, including renal failure, hyperkalemia, angioedema, and increased reports of sudden cardiac death. It highlights the need for rigorous monitoring and precise treatment regimens, especially in diabetic heart failure patients. Additionally, the review questions the generalizability of the study's results to diverse healthcare settings and emphasizes the importance of grounded patient follow-up data for accurate long-term assessment. These considerations are vital for informed decision-making regarding sacubitril/valsartan use in heart failure management.}, } @article {pmid37732867, year = {2022}, author = {Hui, CL}, title = {Research on maintenance treatment to prevent relapse of psychotic disorders.}, journal = {Psychiatry research}, volume = {317}, number = {}, pages = {114928}, doi = {10.1016/j.psychres.2022.114928}, pmid = {37732867}, issn = {1872-7123}, mesh = {Humans ; *Antipsychotic Agents/adverse effects ; *Psychotic Disorders/drug therapy ; Chronic Disease ; Antisocial Personality Disorder ; Recurrence ; }, abstract = {The issue of antipsychotic (dis)continuation has been a long-standing clinical dilemma. While the routine usage of antipsychotic is associated with side effects and stigma, short-term evidence suggest that the risk of relapse is heightened following antipsychotics withdrawal. Clinical guidelines therefore propose a one to two years duration of maintenance treatment upon remission in first episode psychosis (FEP), but guidance beyond which remains unclear. Only two controlled studies have addressed the long-term consequences of antipsychotic discontinuation. While Wunderink et al. concluded that dose reduction is associated with a higher rate of recovery, Hui et al. found discontinuation to be associated with better clinical outcomes. Data from Hui et al.'s study further suggests that treatment should be maintained for at least the first three years upon remission in FEP in order reduce the risk of relapse, as well as subsequent poor long-term outcome. It is noted that the two studies not only differ in outcome measures, but also in their strategies of "antipsychotic discontinuation". Considering that discontinuation is a more compelling option to most patients, it may therefore be more clinically relevant. More long-term follow-up discontinuation studies are needed to provide further evidence in the development of treatment guidelines for FEP.}, } @article {pmid37726779, year = {2023}, author = {Wang, Y and Wong, EL and Nilsen, P and Chung, VC and Tian, Y and Yeoh, EK}, title = {A scoping review of implementation science theories, models, and frameworks - an appraisal of purpose, characteristics, usability, applicability, and testability.}, journal = {Implementation science : IS}, volume = {18}, number = {1}, pages = {43}, pmid = {37726779}, issn = {1748-5908}, mesh = {Humans ; *Implementation Science ; Databases, Factual ; }, abstract = {BACKGROUND: A proliferation of theories, models, and frameworks (TMFs) have been developed in the implementation science field to facilitate the implementation process. The basic features of these TMFs have been identified by several reviews. However, systematic appraisals on the quality of these TMFs are inadequate. To fill this gap, this study aimed to assess the usability, applicability, and testability of the current TMFs in a structured way.

METHODS: A scoping review method was employed. Electronic databases were searched to locate English and Chinese articles published between January 2000 and April 2022. Search terms were specific to implementation science. Additionally, hand searches were administered to identify articles from related reviews. Purpose and characteristics such as the type of TMF, analytical level, and observation unit were extracted. Structured appraisal criteria were adapted from Birken et al.'s Theory Comparison and Selection Tool (T-CaST) to conduct an in-depth analysis of the TMFs' usability, applicability, and testability.

RESULTS: A total of 143 TMFs were included in this analysis. Among them, the most common purpose was to identify barriers and facilitators. Most TMFs applied the descriptive method to summarize the included constructs or the prescriptive method to propose courses of implementation actions. TMFs were mainly mid-range theories built on existing conceptual frameworks or demonstrated grand theories. The usability of the TMFs needs to be improved in terms of the provision of conceptually matched strategies to barriers and facilitators and instructions on the TMFs usage. Regarding the applicability, little attention was paid to the constructs of macro-level context, stages of scale-up and sustainability, and implementation outcomes like feasibility, cost, and penetration. Also, fewer TMFs could propose recommended research and measurement methods to apply the TMFs. Lastly, explicit hypotheses or propositions were lacking in most of the TMFs, and empirical evidence was lacking to support the claimed mechanisms between framework elements in testability.

CONCLUSIONS: Common limitations were found in the usability, application, and testability of the current TMFs. The findings of this review could provide insights for developers of TMFs for future theoretical advancements.}, } @article {pmid37720931, year = {2023}, author = {Martínez-Camarena, Á and Sour, A and Faller, P}, title = {Impact of human serum albumin on Cu[II] and Zn[II] complexation by ATSM (diacetyl-bis(N4-methylthiosemicarbazone)) and a water soluble analogue.}, journal = {Dalton transactions (Cambridge, England : 2003)}, volume = {52}, number = {38}, pages = {13758-13768}, doi = {10.1039/d3dt02380j}, pmid = {37720931}, issn = {1477-9234}, mesh = {Humans ; *Coordination Complexes ; *Organometallic Compounds/chemistry ; Diacetyl ; Serum Albumin, Human ; Ligands ; Zinc ; *Thiosemicarbazones/chemistry ; Copper Radioisotopes ; Radiopharmaceuticals ; }, abstract = {The chelator diacetyl-bis(N4-methylthiosemicarbazone) (ATSM) and its complexes with Cu[II] and Zn[II] are becoming increasingly investigated for medical applications such as PET imaging for anti-tumour therapy and the treatment of amyotrophic lateral sclerosis. However, the solubility in water of both the ligand and the complexes presents certain limitations for in vitro studies. Moreover, the stability of the Cu[II] and Zn[II] complexes and their metal exchange reaction against the potential biological competitor human serum albumin (HSA) has not been studied in depth. In this work it was observed that the ATSM with an added carboxylic group into the structure increases its solubility in aqueous solutions without altering the coordination mode and the conjugated system of the ligand. The poorly water-soluble Cu[II]- and Zn[II]-ATSM complexes were prevented from precipitating due to the binding to HSA. Both HSA and ATSM show a similar thermodynamic affinity for Zn[II]. Finally, the Cu[II]-competition experiments with EDTA and the water-soluble ATSM ligands yielded an apparent log Kd at pH 7.4 of about -19. When ATSM was added to Cu[II]- and Zn[II]-loaded HSA, withdrawing of Zn[II] was kinetically favoured, but this metal is slowly substituted by the Cu[II] afterwards taken from HSA so that this protein could be considered as a source of Cu[II] for ATSM.}, } @article {pmid37719300, year = {2023}, author = {Kittle, S}, title = {The Conditional Analysis of the Agentive Modals: a Reply to Mandelkern et al.}, journal = {Philosophia (Ramat-Gan, Israel)}, volume = {51}, number = {4}, pages = {2117-2138}, pmid = {37719300}, issn = {1574-9274}, abstract = {A proper understanding of agentive modals promises to clarify issues to do with free will, know how, and other philosophically interesting topics. In this paper I identify one constraint on, and one structural feature of, trying-based versions of the conditional analysis of the agentive modals. I suggest that the constraint and structural feature together provide a novel account of why the famous Lehrer-Chisholm objection to conditional analyses of ability modals is so powerful. I argue that Mandelkern et al.'s 'Agentive Modals' (Philosophical Review, 126/3, 301-343, 2017) conditional analysis of the agentive modals fails to avoid this problem. I also identify two further problems for their account. I close by summarising a number of criteria which any successful semantic analysis of the agentive modals should satisfy.}, } @article {pmid37718822, year = {2023}, author = {Chen, S and Wang, Y and Mueller, C}, title = {Code-Based Algorithms for Identifying Dementia in Electronic Health Records: Bridging the Gap Between Theory and Practice.}, journal = {Journal of Alzheimer's disease : JAD}, volume = {95}, number = {3}, pages = {941-943}, doi = {10.3233/JAD-230887}, pmid = {37718822}, issn = {1875-8908}, mesh = {Humans ; Electronic Health Records ; *Cognitive Dysfunction ; Delivery of Health Care ; Algorithms ; *Dementia/diagnosis ; }, abstract = {Code-based algorithms are crucial tools in the detection of dementia using electronic health record data, with broad applications in medical research and healthcare. Vassilaki et al.'s study explores the efficacy of code-based algorithms in dementia detection using electronic health record data, achieving approximately 70% sensitivity and positive predictive value. Despite the promising results, the algorithms fail to detect around 30% of dementia cases, highlighting challenges in distinguishing cognitive decline factors. The study emphasizes the need for algorithmic improvements and further exploration across diverse healthcare systems and populations, serving as a critical step toward bridging gaps in dementia care and understanding.}, } @article {pmid37717544, year = {2023}, author = {Findley, E}, title = {"It's already stressful being a foster parent": A qualitative inquiry into foster parenting stress during COVID-19.}, journal = {Child abuse & neglect}, volume = {146}, number = {}, pages = {106455}, doi = {10.1016/j.chiabu.2023.106455}, pmid = {37717544}, issn = {1873-7757}, mesh = {Humans ; *Parenting ; Pandemics ; *COVID-19/epidemiology ; Parents ; Foster Home Care ; }, abstract = {BACKGROUND: Emerging literature suggests parents were under increased stress as a result of the COVID-19 pandemic; however, fewer studies to date have examined the wellbeing of foster parents in this season. Miller et al.'s (2020) quantitative study recommended in-depth, qualitative study of the stressors faced by foster parents during COVID-19.

OBJECTIVE: Accordingly, this qualitative study sought to fill a gap in the literature regarding foster parents' lived experiences of foster parenting stress during the COVID-19 pandemic.

PARTICIPANTS AND SETTING: Virtual, semi-structured interviews were conducted with n = 20 foster parents from across one Southern U.S. state between April and July 2021.

METHODS: Verbatim transcripts were analyzed utilizing Braun and Clarke's (2006) thematic analysis.

RESULTS: Five themes emerged in the analysis: (1) Varied Descriptions of Fostering in a Pandemic; (2) Nowhere to Go; (3) COVID-Consciousness; (4) The Virtual Reality; and (5) Stress Relief. Eight total additional subthemes were recorded. All themes and subthemes were described with representative direct quotations from the data.

CONCLUSIONS: Findings from this study demonstrated foster parents experienced both shared and unique parenting challenges during COVID-19. Three areas for further consideration and development in practice included improving online service delivery, strengthening guidance for online parent-child visitation, and enhancing support for foster parents of children with special needs. Developing social support and self-care practices should continue to be ongoing priorities for foster parents and foster parent-serving agencies.}, } @article {pmid37714967, year = {2023}, author = {Séguier, D and Villers, A and Olivier, J}, title = {Standardized reports of focal-HIFU results is paramount: a closer look at the Duwe et al.'s cohort on focal HIFU for localized prostate cancer.}, journal = {World journal of urology}, volume = {41}, number = {10}, pages = {2873-2874}, pmid = {37714967}, issn = {1433-8726}, mesh = {Male ; Humans ; Prospective Studies ; *Prostatic Neoplasms/surgery ; *Ultrasound, High-Intensity Focused, Transrectal ; Patients ; }, } @article {pmid37701627, year = {2023}, author = {Tipton, E and Bryan, C and Murray, J and McDaniel, M and Schneider, B and Yeager, DS}, title = {Why Meta-Analyses of Growth Mindset and Other Interventions Should Follow Best Practices for Examining Heterogeneity: Commentary on Macnamara and Burgoyne (2023) and Burnette et al. (2023).}, journal = {Psychological bulletin}, volume = {149}, number = {3-4}, pages = {229-241}, pmid = {37701627}, issn = {1939-1455}, support = {P2C HD042849/HD/NICHD NIH HHS/United States ; R01 HD084772/HD/NICHD NIH HHS/United States ; R24 HD042849/HD/NICHD NIH HHS/United States ; }, abstract = {Meta-analysts often ask a yes-or-no question: Is there an intervention effect or not? This traditional, all-or-nothing thinking stands in contrast with current best practice in meta-analysis, which calls for a heterogeneity-attuned approach (i.e., focused on the extent to which effects vary across procedures, participant groups, or contexts). This heterogeneity-attuned approach allows researchers to understand where effects are weaker or stronger and reveals mechanisms. The current article builds on a rare opportunity to compare two recent meta-analyses that examined the same literature (growth mindset interventions) but used different methods and reached different conclusions. One meta-analysis used a traditional approach (Macnamara and Burgoyne, in press), which aggregated effect sizes for each study before combining them and examined moderators one-by-one by splitting the data into small subgroups. The second meta-analysis (Burnette et al., in press) modeled the variation of effects within studies-across subgroups and outcomes-and applied modern, multi-level meta-regression methods. The former concluded that growth mindset effects are biased, but the latter yielded nuanced conclusions consistent with theoretical predictions. We explain why the practices followed by the latter meta-analysis were more in line with best practices for analyzing large and heterogeneous literatures. Further, an exploratory re-analysis of the data showed that applying the modern, heterogeneity-attuned methods from Burnette et al. (in press) to the dataset employed by Macnamara and Burgoyne (in press) confirmed Burnette et al.'s conclusions; namely, that there was a meaningful, significant effect of growth mindset in focal (at-risk) groups. This article concludes that heterogeneity-attuned meta-analysis is important both for advancing theory and for avoiding the boom-or-bust cycle that plagues too much of psychological science.}, } @article {pmid37695099, year = {2023}, author = {Chu, WM and Hsieh, TH and Wei, JC}, title = {Comment on Tsai et al.'s "clinical effectiveness of oral antiviral agents in older patients with COVID-19 based on real-world data".}, journal = {Journal of medical virology}, volume = {95}, number = {9}, pages = {e29086}, doi = {10.1002/jmv.29086}, pmid = {37695099}, issn = {1096-9071}, mesh = {Humans ; Aged ; *COVID-19 ; Treatment Outcome ; }, } @article {pmid37691053, year = {2023}, author = {Amaral, L and Oliveira, F and Oliveira, C}, title = {The Meaning of Inchoative se in Brazilian Portuguese: A Replication of Lundquist et al.'s (2016) Experiment.}, journal = {Journal of psycholinguistic research}, volume = {52}, number = {6}, pages = {2567-2598}, pmid = {37691053}, issn = {1573-6555}, support = {APQ-00693-18//fapemig/ ; }, mesh = {Humans ; Child ; *Semantics ; Brazil ; *Language ; Child Language ; Language Tests ; }, abstract = {In the well-known causative alternation, a verb appears either in a causative-transitive or in an inchoative-intransitive form. The inchoative form is marked with a reflexive clitic in some languages, such as Norwegian, but is unmarked in others, such as English. There are two main proposals to explain the alternation: a lexical-derivational account (a lexical rule is responsible for the demotion of the cause argument), and a syntactic-derivational one (in a type of reflexivization, the theme/patient is construed as responsible for causing the event). A third type of approach posits that the alternation emerges when a verb can be found in different constructions and no derivation is involved. Lundquist et al. (Glossa J Gen Linguist 1:1-30, 2016) put the first two approaches to experimental testing and found that while the decausativization approach is adequate for English, the reflexivization approach explains the Norwegian facts. The present experimental study investigates which proposal is adequate to explain the alternation in Brazilian Portuguese. Differently from both English and Norwegian, Brazilian Portuguese allows reflexive-marked and unmarked inchoatives with the same verb. In a replication of Lundquist et al.'s (Glossa J Gen Linguist 1:1-30, 2016) experiment, our results show that Brazilian Portuguese assigns distinct meanings to the two forms of the inchoative. We conclude that the reflexive pronoun se indicates that the change of state described in the inchoative sentence was caused by some entity, but not an agent. We then argue that a non-derivational approach explains the alternation, as a single verb occurs in distinct syntactic configurations, with distinct meaning implications.}, } @article {pmid37690961, year = {2023}, author = {Castro-Santos, P and Carracedo, Á and Díaz-Peña, R}, title = {HLA alleles: important pieces to the COVID-19 puzzle.}, journal = {Trends in immunology}, volume = {44}, number = {10}, pages = {754-756}, doi = {10.1016/j.it.2023.08.011}, pmid = {37690961}, issn = {1471-4981}, mesh = {Humans ; *COVID-19/genetics ; Alleles ; Histocompatibility Antigens Class I/genetics ; HLA Antigens/genetics ; HLA-B Antigens/genetics ; }, abstract = {Research on human leukocyte antigen (HLA) molecules in coronavirus disease 2019 (COVID-19) raised high expectations but has yielded limited results. Augusto et al.'s recent study in Nature unveils a strong association of HLA-B*15:01 with asymptomatic COVID-19, representing an important contribution to genetics in COVID-19.}, } @article {pmid37679738, year = {2023}, author = {Birkeli, CN and Normand, C and Rø, KI and Kvernenes, M}, title = {Educational supervision in internal medicine residency training - a scoping review.}, journal = {BMC medical education}, volume = {23}, number = {1}, pages = {644}, pmid = {37679738}, issn = {1472-6920}, mesh = {Humans ; *Internship and Residency ; Educational Status ; Learning ; *Mentoring ; Internal Medicine ; }, abstract = {BACKGROUND: Although supervision is an important part of residency training, its scope and how it relates to other types of support, such as mentoring, precepting and feedback, remain unclear. While clinical supervision consists of ongoing instructions and feedback in the workplace setting, educational supervision is a formalized component of postgraduate medical educational and supports the process that facilitates a trainee's progression throughout their training. Since medical specialties have different supervisory traditions, this study focuses on educational supervision in internal medicine. Our aim was to investigate what is known about educational supervision practices in internal medicine and the role of educational supervision in supporting residents' learning.

METHODS: We conducted a scoping review of the literature on educational supervision in residency training in internal medicine based on Levac et al.'s modification of Arksey and O'Malley's six-step framework. The literature search was performed in the following databases: Medline, Embase, Web of Science and the Educational Resources Information Center. In addition, we conducted a handsearch in Medical Teacher and Google Scholar. We followed the PRISMA guidelines for systematic research.

RESULTS: Eighteen of the 3,284 identified articles were included in the analysis. We found few empirical studies describing how educational supervision is conducted and what effect routine educational supervision has on residents' learning. Our findings suggest that the terminology can be confusing and that educational supervision practices in internal medicine has a weak theoretical foundation.

CONCLUSION: The distinction between educational supervision and other support structures, such as mentoring and feedback, has not been clearly defined in the research literature. We argue that shared terminology is needed to better understand current educational practices and to facilitate clear communication about how to help residents learn.}, } @article {pmid37669153, year = {2023}, author = {Hui, V and Litton, E and Edibam, C and Geldenhuys, A and Hahn, R and Larbalestier, R and Wright, B and Pavey, W}, title = {Using machine learning to predict bleeding after cardiac surgery.}, journal = {European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery}, volume = {64}, number = {6}, pages = {}, doi = {10.1093/ejcts/ezad297}, pmid = {37669153}, issn = {1873-734X}, mesh = {Humans ; Australia/epidemiology ; *Machine Learning ; *Cardiac Surgical Procedures/adverse effects ; Hemorrhage ; Heart ; Retrospective Studies ; }, abstract = {OBJECTIVES: The primary objective was to predict bleeding after cardiac surgery with machine learning using the data from the Australia New Zealand Society of Cardiac and Thoracic Surgeons Cardiac Surgery Database, cardiopulmonary bypass perfusion database, intensive care unit database and laboratory results.

METHODS: We obtained surgical, perfusion, intensive care unit and laboratory data from a single Australian tertiary cardiac surgical hospital from February 2015 to March 2022 and included 2000 patients undergoing cardiac surgery. We trained our models to predict either the Papworth definition or Dyke et al.'s universal definition of perioperative bleeding. Our primary outcome was the performance of our machine learning algorithms using sensitivity, specificity, positive and negative predictive values, accuracy, area under receiver operating characteristics curve (AUROC) and area under precision-recall curve (AUPRC).

RESULTS: Of the 2000 patients undergoing cardiac surgery, 13.3% (226/2000) had bleeding using the Papworth definition and 17.2% (343/2000) had moderate to massive bleeding using Dyke et al.'s definition. The best-performing model based on AUPRC was the Ensemble Voting Classifier model for both Papworth (AUPRC 0.310, AUROC 0.738) and Dyke definitions of bleeding (AUPRC 0.452, AUROC 0.797).

CONCLUSIONS: Machine learning can incorporate routinely collected data from various datasets to predict bleeding after cardiac surgery.}, } @article {pmid37668567, year = {2023}, author = {Lupker, SJ and Spinelli, G}, title = {An examination of models of reading multi-morphemic and pseudo multi-morphemic words using sandwich priming.}, journal = {Journal of experimental psychology. Learning, memory, and cognition}, volume = {49}, number = {11}, pages = {1861-1880}, doi = {10.1037/xlm0001289}, pmid = {37668567}, issn = {1939-1285}, support = {//Natural Sciences and Engineering Research Council/ ; }, mesh = {Humans ; *Semantics ; *Reading ; Pattern Recognition, Visual ; Perceptual Masking ; Reaction Time ; }, abstract = {Rastle et al. (2004) reported that true (e.g., walker) and pseudo (e.g., corner) multi-morphemic words prime their stem words more than form controls do (e.g., brothel priming BROTH) in a masked priming lexical decision task. This data pattern has led a number of models to propose that both of the former word types are "decomposed" into their stem (e.g., walk, corn) and affix (e.g., -er) early in the reading process. The present experiments were designed to examine the models proposed to explain Rastle et al.'s effect, including models not assuming a decomposition process, using a more sensitive priming technique, sandwich priming (Lupker & Davis, 2009). Experiment 1, using the conventional masked priming procedure, replicated Rastle et al.'s results. Experiments 2 and 3, involving sandwich priming procedures, showed a clear dissociation between priming effects for true versus pseudo multi-morphemic words, results that are not easily explained by any of the current models. Nonetheless, the overall data pattern does appear to be most consistent with there being a decomposition process when reading real and pseudo multi-morphemic words, a process that involves activating (and inhibiting) lexical-level representations including a representation for the affix (e.g., -er), with the ultimate lexical decision being based on the process of resolving the pattern created by the activated representational units. (PsycInfo Database Record (c) 2023 APA, all rights reserved).}, } @article {pmid37658452, year = {2023}, author = {Tsuda, T and Miyano, Y and Yamamoto, E}, title = {Mistaken information can lead only to misguided conclusions and policies: a commentary regarding Schüz et al.'s response.}, journal = {Environmental health : a global access science source}, volume = {22}, number = {1}, pages = {62}, pmid = {37658452}, issn = {1476-069X}, mesh = {Adolescent ; Adult ; Child ; Humans ; Environmental Health ; Japan ; *Lead ; Policy ; *Thyroid Neoplasms/epidemiology ; Review Literature as Topic ; }, abstract = {BACKGROUND: After reviewing selected scientific evidence, Schüz et al. made two recommendations in the 2018 International Agency for Research on Cancer (IARC) Technical Publication No. 46. Their first recommendation was against population thyroid screening after a nuclear accident, and the second was that consideration be given to offering a long-term thyroid monitoring program for higher-risk individuals (100-500 mGy or more radiation) after a nuclear accident. However, their review of the scientific evidence was inadequate and misrepresented the information from both Chernobyl and Fukushima. We wrote a review article published in Environmental Health in 2022 using the "Toolkit for detecting misused epidemiological methods." Schüz et al. critiqued our 2022 review article in 2023; their critique, based also on their 2018 IARC Technical Publication No. 46, was so fraught with problems that we developed this response.

MAIN BODY: Schüz et al. suggest that hundreds of thyroid cancer cases in children and adolescents, detected through population thyroid examinations using ultrasound echo and conducted since October 2011 in Fukushima, were not caused by the 2011 Fukushima Daiichi Nuclear Power Plant accident. Schüz et al. compared thyroid cancers in Fukushima directly with those in Chernobyl after April 1986 and listed up to five reasons to deny a causal relationship between radiation and thyroid cancers in Fukushima; however, those reasons we dismiss based on available evidence. No new scientific evidence was presented in their response to our commentary in which we pointed out that misinformation and biased scientific evidence had formed the basis of their arguments. Their published article provided erroneous information on Fukushima. The article implied overdiagnosis in adults and suggested that overdiagnosis would apply to current Fukushima cases. The IARC report did not validate the secondary confirmatory examination in the program which obscures the fact that overdiagnosis may not have occurred as much in Fukushima. The report consequently precluded the provision of important information and measures.

CONCLUSION: Information provided in the IARC Technical Publication No. 46 was based on selected scientific evidence resulting in both public and policy-maker confusion regarding past and present nuclear accidents, especially in Japan. It should be withdrawn.}, } @article {pmid37650790, year = {2024}, author = {Payne, JW and Schimmack, U}, title = {Valence explains how and why positive affects and negative affects correlate: A conceptual replication and extension of Diener et al.'s (1995) the personality structure of affect.}, journal = {Emotion (Washington, D.C.)}, volume = {24}, number = {2}, pages = {522-530}, doi = {10.1037/emo0001281}, pmid = {37650790}, issn = {1931-1516}, support = {//Social Sciences and Humanities Research Council of Canada/ ; }, mesh = {Adult ; Middle Aged ; Humans ; *Personality ; Neuroticism ; *Extraversion, Psychological ; Students ; }, abstract = {Diener et al. (1995) used a multimethod approach to test a hierarchical model of trait affect. The model suggests that specific trait affects are related to each other by two, distinct, but negatively correlated factors. We report the results of a conceptual replication study that addressed several limitations of Diener et al.'s (1995) study. We used three ethnically diverse samples which included a group of undergraduates along with both of their biological parents. As such, in terms of generalizability, we improved upon the original study which was limited to a student sample by also including middle-aged adults as targets. Most importantly, we included measures of hedonic tone to validate the interpretation of the higher-order factors as positive affect and negative affect. Also, we did not average informant ratings to model individual rating biases. Further, we used item-level indicators rather than item averages as indicators of basic affects. Our results confirm Diener et al.'s (1995) model and demonstrate that positive trait affect and negative trait affect are negatively correlated and account for the covariance among specific affects. We discuss the implications of these results in the context of personality theories that consider positive trait affect and negative trait affect as independent factors related to extraversion and neuroticism, respectively (Costa & McCrae, 1980). We argue that this model cannot account for the negative correlation between positive affect and negative affect and that further research is needed to locate affect within the Big Five model of personality. (PsycInfo Database Record (c) 2024 APA, all rights reserved).}, } @article {pmid37650250, year = {2023}, author = {Szabó, D and Békés, V and Lévay, EE and Salgó, E and Unoka, ZS}, title = {Moral injury in psychiatric patients with personality and other clinical disorders: development, psychometric properties, and validity of the Moral Injury Events Scale-Civilian Version.}, journal = {European journal of psychotraumatology}, volume = {14}, number = {2}, pages = {2247227}, pmid = {37650250}, issn = {2000-8066}, mesh = {Adult ; Humans ; Female ; Male ; *Stress Disorders, Post-Traumatic/diagnosis ; Cross-Sectional Studies ; *Non-alcoholic Fatty Liver Disease ; Psychometrics ; Personality Disorders ; Personality ; }, abstract = {Background: Moral injury emerges when someone perpetrates, fails to prevent, or witnesses acts that violate their own moral or ethical code. Nash et al. [(2013). Psychometric evaluation of the moral injury events scale. Military Medicine, 178(6), 646-652] developed a short measure, the Moral Injury Events Scale (MIES) to facilitate the empirical study of moral injury in the military. Our study aimed to develop a civilian version of the measure (MIES-CV) and examine its psychometric properties in a sample of psychiatric inpatients .Methods: In this cross-sectional study, the sample comprised 240 adult patients (71.7% female) with a mean age of 31.57 (SD = 11.69). The most common diagnoses in the sample were anxiety disorders (58.3%), depressive disorders (53.8%), and borderline personality disorder (39.6%). Participants were diagnosed using structured clinical interviews and filled out psychological questionnaires.Results: Exploratory factor analysis suggested that Nash et al.'s model (Perceived Transgressions, Perceived Betrayals) represents the data well. This two-factor solution showed an excellent fit in the confirmatory factor analysis, as well. Meaningful associations were observed between moral injury and psychopathology dimensions, shame, reflective functioning, well-being, and resilience. The Perceived Betrayals factor was a significant predictor of bipolar disorders, PTSD, paranoid personality disorder, borderline personality disorder, and avoidant personality disorder.Conclusions: Our study demonstrated that this broad version of the MIES is a valid measure of moral injury that can be applied to psychiatric patients.}, } @article {pmid37648065, year = {2023}, author = {Novice, M and Shapiro, J and Lo Sicco, KI}, title = {Response to Corona-Rodarte et al.'s "Pressure alopecias: a review".}, journal = {Journal of the American Academy of Dermatology}, volume = {89}, number = {6}, pages = {e285-e287}, doi = {10.1016/j.jaad.2023.08.062}, pmid = {37648065}, issn = {1097-6787}, mesh = {Humans ; *Alopecia ; *Folliculitis ; }, } @article {pmid37647882, year = {2023}, author = {Stegwee, SI and Verberkt, C and Huirne, JAF}, title = {Letter on Genovese et al.'s "Impact of Hysterotomy Closure Technique on Subsequent Cesarean Scar Defects Formation: A Systematic Review".}, journal = {Gynecologic and obstetric investigation}, volume = {88}, number = {5}, pages = {322-324}, pmid = {37647882}, issn = {1423-002X}, mesh = {Female ; Humans ; Pregnancy ; *Cicatrix ; *Hysterotomy ; }, } @article {pmid37645636, year = {2023}, author = {Kovačić Petrović, Z and Peraica, T and Blažev, M and Kozarić-Kovačić, D}, title = {Association between problematic Internet use and specific Internet activities and COVID-19- and earthquake-related stress, anxiety, and depression symptoms among Croatian young adults.}, journal = {Frontiers in psychiatry}, volume = {14}, number = {}, pages = {1227182}, pmid = {37645636}, issn = {1664-0640}, abstract = {BACKGROUND: During the COVID-19 pandemic and concomitant earthquakes in Croatia in 2020, increased Internet use (IU) and Internet-based addictive behaviors were associated with decreasing mental well-being. We determined the changes in IU, problematic IU (PIU), and problematic specific Internet activities in young adults during the prolonged stress caused by the pandemic and earthquakes, age differences in PIU and differences in perceived source of stress (pandemic or earthquakes), and association between PIU and increase in specific Internet activities and stress, anxiety, and depression symptoms in young adults.

METHODS: A cross-sectional online survey conducted from September 30, 2021 to October 17, 2021 included 353 young adults aged 22.6 ± 2.1 years, 382 early adults aged 32.1 ± 4.4 years, and 371 middle-aged adults aged 49.0 ± 6.5 years. Data on sociodemographic characteristics, stressors (without perceived stressors, only pandemic-related stressor, only earthquake-related stressor, and both pandemic and earthquake-related stressors), PIU and IU were collected with a self-report questionnaire. The Impact of Event Scale and the Hospital Anxiety Depression Scale were used to evaluate mental symptoms. PIU and problematic specific Internet activities were assessed using Tao et al.'s criteria. Data were anaylzed with paired-sample Wilcoxon test, McNemar's and Pearson's chi-square tests, and structural equation modeling.

RESULTS: In 17% of young adults, we found increased PIU (OR = 5.15, 95% CI [2.82, 10.18]), problematic social media use (OR = 2.77, 95% CI [1.56, 5.14]), and uncontrolled online shopping (OR = 5.75, 95% CI [1.97, 22.87]) (p < 0.001 for all). PIU and problematic social media use were more common among young adults (60.8%), as well as problematic online gaming (25.9%). Problematic social media use was more frequent among young adults reporting pandemic stress than among those without perceived stress (69.9% vs. 43.2%). Increased online gaming predicted more severe avoidance symptoms (p = 0.041), increased social media use predicted more severe depression symptoms (p = 0.017), increased online shopping predicted more severe intrusion (p = 0.013) and anxiety symptoms (p = 0.001). PIU predicted more severe intrusion (p = 0.008), avoidance (p = 0.01), anxiety (p < 0.001), and depression (p = 0.012) symptoms.

CONCLUSION: Different effects of the pandemic and earthquakes on IU could reflect a different effect of various stressors on Internet behavior of young adults. Type of problematic Internet behavior may predict for the type of mental health problem.}, } @article {pmid37633493, year = {2023}, author = {Heard, JC and Lee, Y and Ezeonu, T and Lambrechts, MJ and Issa, TZ and Yalla, GR and Tran, K and Singh, A and Purtill, C and Somers, S and Becsey, A and Canseco, JA and Kurd, MF and Kaye, ID and Hilibrand, AS and Vaccaro, AR and Schroeder, GD and Kepler, CK}, title = {Does the Severity of Foraminal Stenosis Impact Outcomes of Lumbar Decompression Surgery?.}, journal = {World neurosurgery}, volume = {179}, number = {}, pages = {e296-e304}, doi = {10.1016/j.wneu.2023.08.081}, pmid = {37633493}, issn = {1878-8769}, mesh = {Humans ; Constriction, Pathologic/diagnostic imaging/surgery/etiology ; *Spinal Stenosis/complications/diagnostic imaging/surgery ; Retrospective Studies ; *Radiculopathy/diagnostic imaging/etiology/surgery ; Decompression, Surgical/methods ; Lumbar Vertebrae/diagnostic imaging/surgery ; Treatment Outcome ; }, abstract = {OBJECTIVE: To establish the relationship between the magnitude of foraminal stenosis and 1) improvement in patient-reported outcomes, 2) improvement in motor function after lumbar decompression surgery, and 3) difference in surgical outcomes.

METHODS: Patients who underwent one-level posterior lumbar decompression for radiculopathy were retrospectively identified. Patient demographics and surgical characteristics were collected through a query search and manual chart review of the electronic medical records. Foraminal stenosis was determined on magnetic resonance imaging and graded using Lee et al.'s validated methodology as none, mild, moderate, or severe. Surgical outcomes, motor function, and patient-reported outcome measures (PROMs) were compared based on the amount of stenosis (mild vs. moderate vs. severe). Bivariant and multivariant analyses were performed.

RESULTS: Severe stenosis demonstrated more 90-day readmissions (0.00% vs. 0.00% vs. 8.57%, respectively, P = 0.019), though this effect did not remain significant on multivariate analysis (P = 0.068). There was no association between stenosis severity and the degree of functional impairment or PROMs preoperatively. Patients with moderate or severe preoperative foraminal stenosis showed improvement in all PROMs after surgery (P < 0.05) except the mental component of the Short Form 12 survey. Notably, central stenosis grade was insignificantly different between groups (P = 0.358). Multivariable logistic regression analysis did not identify any significant independent predictors of surgical outcomes or changes in PROMs.

CONCLUSIONS: We demonstrated that regardless of foraminal stenosis severity preoperatively, patients have a similar improvement in PROMs, surgical outcomes, and restoration of motor function after lumbar decompression surgery for radiculopathy.}, } @article {pmid37626309, year = {2023}, author = {Li, M and Gao, Q and Yu, T}, title = {Kappa statistic considerations in evaluating inter-rater reliability between two raters: which, when and context matters.}, journal = {BMC cancer}, volume = {23}, number = {1}, pages = {799}, pmid = {37626309}, issn = {1471-2407}, support = {145209121//Fundamental Research Funds in Heilongjiang Provincial Universities/ ; HLJ2019017//Chinese Ministry of Education "Chunhui Plan" International Scientific Research Cooperation Project/ ; Not applicable.//Heilongjiang Province Leading Talent Echelon Reserve Leader Funding Project/ ; }, mesh = {Humans ; Reproducibility of Results ; *Research Design ; *Upper Extremity ; }, abstract = {BACKGROUND: In research designs that rely on observational ratings provided by two raters, assessing inter-rater reliability (IRR) is a frequently required task. However, some studies fall short in properly utilizing statistical procedures, omitting essential information necessary for interpreting their findings, or inadequately addressing the impact of IRR on subsequent analyses' statistical power for hypothesis testing.

METHODS: This article delves into the recent publication by Liu et al. in BMC Cancer, analyzing the controversy surrounding the Kappa statistic and methodological issues concerning the assessment of IRR. The primary focus is on the appropriate selection of Kappa statistics, as well as the computation, interpretation, and reporting of two frequently used IRR statistics when there are two raters involved.

RESULTS: The Cohen's Kappa statistic is typically utilized to assess the level of agreement between two raters when there are two categories or for unordered categorical variables with three or more categories. On the other hand, when it comes to evaluating the degree of agreement between two raters for ordered categorical variables comprising three or more categories, the weighted Kappa is a widely used measure.

CONCLUSION: Despite not substantially affecting the findings of Liu et al.?s study, the statistical dispute underscores the significance of employing suitable statistical methods. Rigorous and accurate statistical results are crucial for producing trustworthy research.}, } @article {pmid37621279, year = {2023}, author = {Thijs, Z and Dumican, M}, title = {Laryngeal symptoms related to motor phenotypes in Parkinson's disease: A systematic review.}, journal = {Laryngoscope investigative otolaryngology}, volume = {8}, number = {4}, pages = {970-979}, pmid = {37621279}, issn = {2378-8038}, abstract = {OBJECTIVE: This study aimed to systematically review the associations between motor clinical phenotypes in Parkinson's disease (PD) and laryngeal disease symptoms. Laryngeal dysfunctions such as dysphonia and dysphagia are ubiquitous in people with Parkinson's disease (PwPD). Similar to other disease symptoms, they manifest variably across PwPD. Some of the variability within PD has been explained by clinical phenotypes. However, it is unclear how laryngeal symptoms of PD express themselves across these phenotypes.

METHODS: Five databases were searched (MEDLINE, CINAHL, Web of Science, Embase, Scopus) in May 2022. After the removal of duplicates, all retrieved records were screened. Cohort, case-control, and cross-sectional studies in English discussing laryngeal symptoms and clinical PD phenotypes were included. Data were extracted, tabulated, and assessed using Moola et al.'s (2021) appraisal tool for systematic reviews of risk and etiology.

RESULTS: The search retrieved 2370 records, representing 540 PwPD. After the removal of duplicates and screening, eight articles were included for review. The most common phenotype categories were tremor-dominant and postural-instability gait disordered (PIGD). Five studies addressed vocal characteristics, while four considered swallowing. Differences and lack of rigor in methodology across studies complicated conclusions, but a tendency for tremor-dominant phenotypes to present with less severe laryngeal symptoms was found.

CONCLUSION: Some minor differences in laryngeal function were found between tremor-dominant and PIGD phenotypes in PD. However, there is a need for more standardized and high-quality studies when comparing motor phenotypes for laryngeal function.}, } @article {pmid37615263, year = {2024}, author = {McFadyen, A}, title = {'Everyone needs to know that infant mental health is important' - a commentary/reflection on 'Improving access to mental health interventions for children from birth to five years: a scoping review' (Hickey et al., 2023).}, journal = {Child and adolescent mental health}, volume = {29}, number = {1}, pages = {96-98}, doi = {10.1111/camh.12675}, pmid = {37615263}, issn = {1475-357X}, mesh = {Humans ; Infant ; Australia ; *Mental Health ; *Mental Health Services ; Infant, Newborn ; Child, Preschool ; Scoping Reviews As Topic ; }, abstract = {Hickey et al.'s scoping of infant mental health (IMH) services and the challenges faced in ensuring that vulnerable infants can access them highlights important issues and suggests some solutions (Hickey et al., Child and Adolescent Mental Health, 2023). Their synthesis of useful research in the field is limited only by its focus on more affluent English-speaking countries, which is acknowledged. Writing from an Australian perspective, they highlight the need for culturally sensitive service delivery. This commentary draws attention to the concept of candidacy as a helpful way of thinking about patents' journeys into services. It can support a deeper understanding of the barriers to referral for infants most in need. One key issue is the knowledge and understanding of both professionals and the public about the importance of the early years for later well-being. Infants cannot advocate for themselves and depend on those around them to exercise their right to services. Good relationships between professionals and between family members and clinicians are essential for IMH service development and delivery.}, } @article {pmid37608498, year = {2023}, author = {Najafi, F and Mardanian Dehkordi, L and Khodayari, S and Jaafarpour, M and Nasrabadi, AN}, title = {Nurses' bereavement experiences of a deceased colleague due to COVID-19: A phenomenological study.}, journal = {Nursing open}, volume = {10}, number = {11}, pages = {7233-7243}, pmid = {37608498}, issn = {2054-1058}, support = {IR.TUMS.FNM.REC.1399. 568//Tehran University of Medical Sciences and Health Services/ ; }, abstract = {AIM: Healthcare workers have little time to mourn due to the intensification of the COVID-19 pandemic. Although grief is a normal part of life and death, the circumstances surrounding the death can affect the grieving process. So far, the nurses' experience in mourn for a deceased colleague in the COVID-19 pandemic has not been determined. Identifying these experiences can provide opportunities to formulate appropriate strategies to functionally adapt to death and promote mental health and well-being during this crisis. This study aimed to understand the nurses' experiences in mourning for a deceased colleague due to COVID-19.

DESIGN: This was an interpretive phenomenological study.

METHOD: Participants included 10 nurses with the bereavement experience following the death of a colleague due to COVID-19, who were selected through purposive sampling, and the data were collected through in-depth and semi-structured interviews and analysed using Diekelmann et al.'s (1989) approach.

RESULTS: The nurses' bereavement experiences were in the form of eight themes: disbelief and amazement, acceptance with grief, lasting sadness, unsung laments, bringing back memories, impulse to leave the service, a professional myth and holy death. For nurses, mourning for the death of a colleague due to COVID-19 is like a lasting sadness that begins with disbelief and amazement and changes to acceptance with sadness. From the fellow nurses' point of view, this type of death was perceived as a holy death, which along with countless unsung laments and memories brought to us the association of a professional legend, and that such a fate would be inevitable for us as well, it was a push to leave the service.

PUBLIC CONTRIBUTION: Crisis managers and policymakers need to add protocols and training programs for resilience skills and healthy mourning.}, } @article {pmid37591228, year = {2024}, author = {Lai, SW}, title = {Comment on Kang et al.'s "Comparison between the Effects of Allopurinol and Febuxostat on the Survival of Patients on Maintenance Hemodialysis".}, journal = {American journal of nephrology}, volume = {55}, number = {2}, pages = {260-261}, doi = {10.1159/000533172}, pmid = {37591228}, issn = {1421-9670}, mesh = {Humans ; *Febuxostat/therapeutic use ; Allopurinol/therapeutic use ; Gout Suppressants/therapeutic use ; *Hyperuricemia/drug therapy ; Renal Dialysis/adverse effects ; }, } @article {pmid37579672, year = {2023}, author = {Lee, DYH and Shanks, DR}, title = {Conscious and unconscious memory and eye movements in context-guided visual search: A computational and experimental reassessment of Ramey, Yonelinas, and Henderson (2019).}, journal = {Cognition}, volume = {240}, number = {}, pages = {105539}, doi = {10.1016/j.cognition.2023.105539}, pmid = {37579672}, issn = {1873-7838}, mesh = {Humans ; *Eye Movements ; Reproducibility of Results ; *Recognition, Psychology ; Learning ; Consciousness ; }, abstract = {Are eye movements unconsciously guided towards target locations in familiar scenes? In a recent eyetracking study, Ramey, Yonelinas, and Henderson (2019) measured eye-movement efficiency (scanpath ratio) and memory judgments when participants searched for targets in repeated and novel scenes. When trials judged new with high confidence were selected, scanpath ratio was lower for old scenes (misses) than for new scenes (correct rejections). In addition, familiarity as measured by recognition confidence did not significantly predict scanpath ratio. Ramey et al. attributed these results to unconscious learning guiding eye movements. In a re-assessment of Ramey et al.'s data, we show that their findings can be accounted for by a single-system computational model in which eye movements and memory judgments are driven by a common latent memory representation. In particular, (a) the scanpath ratio difference between high-confidence misses and correct rejections is a consequence of regression to the mean, while (b) the null correlation between familiarity and scanpath ratio, partly a natural consequence of the low reliability of the scanpath ratio measure, is also reproduced by the model. Two pre-registered experiments confirm a novel prediction of the alternative single-system model. This work offers a parsimonious account of Ramey et al.'s findings without recourse to unconscious guidance of eye movements.}, } @article {pmid37579347, year = {2022}, author = {Rycroft-Malone, J and Rogers, L and Burton, CR}, title = {Optimising the Conceptualisation of Context Comment on "Stakeholder Perspectives of Attributes and Features of Context Relevant to Knowledge Translation in Health Settings: A Multi-country Analysis".}, journal = {International journal of health policy and management}, volume = {11}, number = {10}, pages = {2365-2367}, pmid = {37579347}, issn = {2322-5939}, mesh = {Humans ; *Concept Formation ; *Translational Science, Biomedical ; }, abstract = {Context matters. Therefore, efforts to develop greater conceptual clarity are important for science and practice. In this commentary, we outline some key issues that were prompted by Squire's et al.'s contribution. Specifically, we reinforce context as an interactive concept and therefore something that is hard to 'pin down', the problematic nature of conceptualising context in implementation and de-implementation, and a requirement for the development of culturally sensitive understandings. Finally, we suggest it is vital that continued investment into providing a more comprehensive list of determinants needs to be accompanied by an equal effort in developing practical methods and tools to support use and application.}, } @article {pmid37573394, year = {2023}, author = {Guan, SW and Lin, Q and Wu, XD and Yu, HB}, title = {Weighted gene coexpression network analysis and machine learning reveal oncogenome associated microbiome plays an important role in tumor immunity and prognosis in pan-cancer.}, journal = {Journal of translational medicine}, volume = {21}, number = {1}, pages = {537}, pmid = {37573394}, issn = {1479-5876}, mesh = {Female ; Humans ; Prognosis ; Gene Regulatory Networks ; *Breast Neoplasms/genetics/pathology ; *Ovarian Neoplasms ; RNA, Messenger ; }, abstract = {BACKGROUND: For many years, the role of the microbiome in tumor progression, particularly the tumor microbiome, was largely overlooked. The connection between the tumor microbiome and the tumor genome still requires further investigation.

METHODS: The TCGA microbiome and genome data were obtained from Haziza et al.'s article and UCSC Xena database, respectively. Separate WGCNA networks were constructed for the tumor microbiome and genomic data after filtering the datasets. Correlation analysis between the microbial and mRNA modules was conducted to identify oncogenome associated microbiome module (OAM) modules, with three microbial modules selected for each tumor type. Reactome analysis was used to enrich biological processes. Machine learning techniques were implemented to explore the tumor type-specific enrichment and prognostic value of OAM, as well as the ability of the tumor microbiome to differentiate TP53 mutations.

RESULTS: We constructed a total of 182 tumor microbiome and 570 mRNA WGCNA modules. Our results show that there is a correlation between tumor microbiome and tumor genome. Gene enrichment analysis results suggest that the genes in the mRNA module with the highest correlation with the tumor microbiome group are mainly enriched in infection, transcriptional regulation by TP53 and antigen presentation. The correlation analysis of OAM with CD8+ T cells or TAM1 cells suggests the existence of many microbiota that may be involved in tumor immune suppression or promotion, such as Williamsia in breast cancer, Biostraticola in stomach cancer, Megasphaera in cervical cancer and Lottiidibacillus in ovarian cancer. In addition, the results show that the microbiome-genome prognostic model has good predictive value for short-term prognosis. The analysis of tumor TP53 mutations shows that tumor microbiota has a certain ability to distinguish TP53 mutations, with an AUROC value of 0.755. The tumor microbiota with high importance scores are Corallococcus, Bacillus and Saezia. Finally, we identified a potential anti-cancer microbiota, Tissierella, which has been shown to be associated with improved prognosis in tumors including breast cancer, lung adenocarcinoma and gastric cancer.

CONCLUSION: There is an association between the tumor microbiome and the tumor genome, and the existence of this association is not accidental and could change the landscape of tumor research.}, } @article {pmid37561512, year = {2024}, author = {Long, M and Rohde, H and Oraa Ali, M and Rubio-Fernandez, P}, title = {The role of cognitive control and referential complexity on adults' choice of referring expressions: Testing and expanding the referential complexity scale.}, journal = {Journal of experimental psychology. Learning, memory, and cognition}, volume = {50}, number = {1}, pages = {109-136}, doi = {10.1037/xlm0001273}, pmid = {37561512}, issn = {1939-1285}, support = {//Research Council of Norway/ ; //Leverhulme Trust/ ; }, mesh = {Humans ; Male ; Female ; Aged ; *Language ; *Linguistics ; Cognition ; Aging/psychology ; Longevity ; }, abstract = {This study aims to advance our understanding of the nature and source(s) of individual differences in pragmatic language behavior over the adult lifespan. Across four story continuation experiments, we probed adults' (N = 496 participants, ages 18-82) choice of referential forms (i.e., names vs. pronouns to refer to the main character). Our manipulations were based on Fossard et al.'s (2018) scale of referential complexity which varies according to the visual properties of the scene: low complexity (one character), intermediate complexity (two characters of different genders), and high complexity (two characters of the same gender). Since pronouns signal topic continuity (i.e., that the discourse will continue to be about the same referent), the use of pronouns is expected to decrease as referential complexity increases. The choice of names versus pronouns, therefore, provides insight into participants' perception of the topicality of a referent, and whether that varies by age and cognitive capacity. In Experiment 1, we used the scale to test the association between referential choice, aging, and cognition, identifying a link between older adults' switching skills and optimal referential choice. In Experiments 2-4, we tested novel manipulations that could impact the scale and found both the TIMING of a competitor referent's presence and EMPHASIS placed on competitors modulated referential choice, leading us to refine the scale for future use. Collectively, Experiments 1-4 highlight what type of contextual information is prioritized at different ages, revealing older adults' preserved sensitivity to (visual) scene complexity but reduced sensitivity to linguistic prominence cues, compared to younger adults. (PsycInfo Database Record (c) 2024 APA, all rights reserved).}, } @article {pmid37545148, year = {2023}, author = {Rimvall, MK and Wesselhoeft, R}, title = {Commentary: Mind the blip in the curve when assessing educational attainment in youths - a reflection on Wickersham et al. (2023).}, journal = {Journal of child psychology and psychiatry, and allied disciplines}, volume = {64}, number = {11}, pages = {1628-1630}, doi = {10.1111/jcpp.13878}, pmid = {37545148}, issn = {1469-7610}, mesh = {Humans ; Adolescent ; Educational Status ; *Academic Success ; *Neurodevelopmental Disorders ; }, abstract = {Dr. Wickersham et al.'s study linked educational and health records providing important knowledge on educational trajectories in youths with mental disorders. They found that youths diagnosed with depression prior to age 18 were more likely to have a decline in educational attainment over time than youths without depression. Furthermore, educational attainment trajectories showed some specificity with different patterns between youths with depression and youths with neurodevelopmental disorders. In this commentary, we highlight the clinical implications of these findings, showing that low or declining educational attainment in youths might serve as a marker for psychopathology, providing the opportunity to identify youths that could benefit from coordinated interventions across diagnostic boundaries.}, } @article {pmid37532603, year = {2024}, author = {Escolà-Gascón, Á and Serra, MV and Houran, J and Dagnall, N and Drinkwater, K and Denovan, A}, title = {Resources on Escolà-Gascón et al.'s (2023) remote viewing research per the original CIA experiments.}, journal = {Explore (New York, N.Y.)}, volume = {20}, number = {1}, pages = {10-16}, doi = {10.1016/j.explore.2023.07.008}, pmid = {37532603}, issn = {1878-7541}, mesh = {Humans ; United States ; *Cognition ; *Intelligence ; }, abstract = {This report describes and presents the raw data from Escolà-Gascón et al.'s[1] remote viewing study, which extended similar experiments initiated by the American Central Intelligence Agency (CIA). Remote viewing is a research technique that allows scientists to examine the degree to which individuals might access "distant (or nonlocal) information" without using known logical-perceptual channels. Many parapsychologists regard such effects as evidence of psychic (or psi) ability, whereas other researchers more cautiously designate beyond-chance results as "anomalous cognition." The original research commissioned by the CIA provided favorable (though highly controversial) results, and several subsequent replications have shown positive and non-significant results. This has fostered heated scientific debate about the nature or meaning of these anomalous cognitions from theoretical, methodological, and statistical viewpoints. This report contextualizes the data obtained from our investigation that conceptually replicated the results of prior remote viewing experiments. Specifically, the authors found a positive association between emotional intelligence (EI) and positive performance (or "hits") in remote viewing cognitive experiments, employing statistical controls based on structural equation modeling (SEM). We thus clarify certain methodological issues about our data to ensure transparency with their future use. We focus on three essential points: (1) more detailed explanation of our EI measures; (2) justification of our effect size calculation and why we obtained underestimated standard deviations per the population parameter; and (3) further consideration of the nuances with interpreting the statistical anomalies (or hits) in the remote viewing tests.}, } @article {pmid37529415, year = {2023}, author = {Smith, MJ and Katikireddi, SV and Skivington, K and Hilton, S}, title = {Contextual influences on the role of evidence in e-cigarette recommendations: a multi-method analysis of international and national jurisdictions.}, journal = {Evidence & policy : a journal of research, debate and practice}, volume = {19}, number = {3}, pages = {400-422}, pmid = {37529415}, issn = {1744-2656}, support = {MC_UU_00022/1/MRC_/Medical Research Council/United Kingdom ; MC_PC_13027/MRC_/Medical Research Council/United Kingdom ; SPHSU18/CSO_/Chief Scientist Office/United Kingdom ; SCAF/15/02/CSO_/Chief Scientist Office/United Kingdom ; MC_UU_00022/3/MRC_/Medical Research Council/United Kingdom ; SPHSU16/CSO_/Chief Scientist Office/United Kingdom ; }, abstract = {BACKGROUND: E-cigarette policy has varied across jurisdictions, contrasting with the previous coordinated approach of international tobacco control communities.

AIMS AND OBJECTIVES: A multi-method case study approach was used to understand the role of evidence and external and internal contextual factors in the development of public health recommendations across four purposively selected jurisdictions (WHO, UK, Australia and USA).

METHODS: Informed by Dobrow et al.'s (2004) conceptual framework for context-based evidencebased decision-making, four data sources were drawn upon: 1) 15 public health bodies' e-cigarette recommendation documents, 2) seven development documents produced by the public health bodies, 3) sources of evidence cited in the public health bodies' recommendation documents and 4) 15 qualitative interviews with experts. Thematic analysis and citation analysis were conducted to aid triangulation of evidence.

FINDINGS: We found a complex interplay between internal and external factors which influence the role and use of evidence in the development of e-cigarette recommendations. For example, recommendation documents' remit (internal factor) was influenced by various external factors such as epidemiology and policy history, with decisions made over time having reshaped the external context. Considering the findings with respect to evidence utilisation, we propose a modified version of Dobrow et al.'s (2004) framework, highlighting the important interplay between internal and external contextual factors.

DISCUSSION AND CONCLUSION: This research suggest internal and external contextual factors mutually interact and influence how evidence is incorporated into recommendations. This dynamic interplay of contextual factors may help explain the why different policy approaches are pursued concerning public health topics, particularly e-cigarettes.}, } @article {pmid37523288, year = {2023}, author = {Wright, AGC and Ringwald, WR and Hopwood, CJ and Pincus, AL}, title = {On definition and description in psychopathology: Reply to Widiger et al. (2023).}, journal = {The American psychologist}, volume = {78}, number = {5}, pages = {716-717}, doi = {10.1037/amp0001172}, pmid = {37523288}, issn = {1935-990X}, mesh = {Humans ; *Personality ; Personality Inventory ; Diagnostic and Statistical Manual of Mental Disorders ; *Personality Disorders/psychology ; International Classification of Diseases ; }, abstract = {We reply to Wright et al.'s (2023) commentary and suggestion that personality trait models would be the preferred way to reconfigure the personality disorders (PDs). Though we agree that personality trait models are powerful descriptive tools, we highlight that they lack definitional or explanatory power, and that is why they have not been able to define or distinguish what PDs are (Hopwood, 2018; Mõttus et al., 2020; Pincus, 2011). Scientific models must do more than describe; they must define. This is why we propose a specific interpersonal model, contemporary integrative interpersonal theory, and why a generic interpersonal model has been formally adopted in psychiatric classification (e.g., International Classification of Diseases; 11th ed.; World Health Organization, 2019) but traits remain optional adjunct descriptors. (PsycInfo Database Record (c) 2023 APA, all rights reserved).}, } @article {pmid37514907, year = {2023}, author = {Mahali, MI and Leu, JS and Darmawan, JT and Avian, C and Bachroin, N and Prakosa, SW and Faisal, M and Putro, NAS}, title = {A Dual Architecture Fusion and AutoEncoder for Automatic Morphological Classification of Human Sperm.}, journal = {Sensors (Basel, Switzerland)}, volume = {23}, number = {14}, pages = {}, pmid = {37514907}, issn = {1424-8220}, mesh = {Male ; Humans ; *Artificial Intelligence ; Reproducibility of Results ; Semen ; *Infertility ; Spermatozoa ; }, abstract = {Infertility has become a common problem in global health, and unsurprisingly, many couples need medical assistance to achieve reproduction. Many human behaviors can lead to infertility, which is none other than unhealthy sperm. The important thing is that assisted reproductive techniques require selecting healthy sperm. Hence, machine learning algorithms are presented as the subject of this research to effectively modernize and make accurate standards and decisions in classifying sperm. In this study, we developed a deep learning fusion architecture called SwinMobile that combines the Shifted Windows Vision Transformer (Swin) and MobileNetV3 into a unified feature space and classifies sperm from impurities in the SVIA Subset-C. Swin Transformer provides long-range feature extraction, while MobileNetV3 is responsible for extracting local features. We also explored incorporating an autoencoder into the architecture for an automatic noise-removing model. Our model was tested on SVIA, HuSHem, and SMIDS. Comparison to the state-of-the-art models was based on F1-score and accuracy. Our deep learning results accurately classified sperm and performed well in direct comparisons with previous approaches despite the datasets' different characteristics. We compared the model from Xception on the SVIA dataset, the MC-HSH model on the HuSHem dataset, and Ilhan et al.'s model on the SMIDS dataset and the astonishing results given by our model. The proposed model, especially SwinMobile-AE, has strong classification capabilities that enable it to function with high classification results on three different datasets. We propose that our deep learning approach to sperm classification is suitable for modernizing the clinical world. Our work leverages the potential of artificial intelligence technologies to rival humans in terms of accuracy, reliability, and speed of analysis. The SwinMobile-AE method we provide can achieve better results than state-of-the-art, even for three different datasets. Our results were benchmarked by comparisons with three datasets, which included SVIA, HuSHem, and SMIDS, respectively (95.4% vs. 94.9%), (97.6% vs. 95.7%), and (91.7% vs. 90.9%). Thus, the proposed model can realize technological advances in classifying sperm morphology based on the evidential results with three different datasets, each having its characteristics related to data size, number of classes, and color space.}, } @article {pmid37510779, year = {2023}, author = {Pirri, C and Biz, C and Pirri, N and Macchi, V and Porzionato, A and De Caro, R and Ruggieri, P and Stecco, C}, title = {Crural and Plantar Fasciae Changes in Chronic Charcot Diabetic Foot: A Cross-Sectional Ultrasound Imaging Study-An Evidence of Fascial Continuity.}, journal = {Journal of clinical medicine}, volume = {12}, number = {14}, pages = {}, pmid = {37510779}, issn = {2077-0383}, abstract = {Crural fascia (CF) and plantar fascia (PF) are biomechanically crucial in the gait and in the proprioception, particularly in the propulsion phase of the foot during the gait cycle and in the dissipation of forces during weight-bearing activities. Recent studies have revealed an association between increases in PF thickness and diabetes. The purpose of this study was to measure and compare by ultrasound (US) imaging the thickness of the CF and PF at different regions/levels in chronic Charcot diabetic foot patients (group 1) and in healthy volunteers (group 2). A cross-sectional study was performed using US imaging to measure the CF with Pirri et al.'s protocol and PF with a new protocol in a sample of 31 subjects (15 patients and 16 healthy participants). The findings for CF and PF revealed statistically significant differences in the poster region of CF (Post 1: group 1 vs. group 2: p = 0.03; Post 2: group 1 vs. group 2: p = 0.03) and in PF at two different levels (PF level 1: group 1 vs. group 2: p < 0.0001; PF level 2: group 1 vs. group 2: p < 0.0001). These findings suggest that chronic Charcot diabetic foot patients have CF and PF thicker compared to healthy volunteers. The US examination suggests that fascial thicknesses behavior in these patients points out altered fascial remodeling due to diabetes pathology and biomechanical changes.}, } @article {pmid37498722, year = {2023}, author = {Oh, IS and Le, H and Roth, PL}, title = {Revisiting Sackett et al.'s (2022) rationale behind their recommendation against correcting for range restriction in concurrent validation studies.}, journal = {The Journal of applied psychology}, volume = {108}, number = {8}, pages = {1300-1310}, doi = {10.1037/apl0001078}, pmid = {37498722}, issn = {1939-1854}, abstract = {Sackett et al. (2022) recommend against correcting for range restriction (RR) in concurrent validation studies. The main rationale behind their recommendation is that unless "rzx" (an unrestricted true-score correlation between the third variable Z where actual selection occurred in a top-down manner [a.k.a., suitability] and the predictor of interest, X) is as high as .90 and selection ratios are as low as .30-both unlikely events in their view, the degree of RR (ux) in concurrent validation studies is unlikely to be low enough (i.e., lower than .90) to warrant RR correction. That is, (a) the "rzx" ≥ .90 and (b) the selection ratio ≤ .30 are two critical conditions for the third condition, (c) ux ≤ .90, a need for RR correction. In this study, we revisit each of these conditions that constitute the rationale behind their recommendation: (a) whether "rzx" is unlikely to be as high as .90; (b) whether selection ratios of .30 or lower are "extreme"; and (c) whether the degree of RR is "little to no" (i.e., ux ≥ .90) in concurrent validation studies, thus no need for correcting for RR in concurrent validation studies. First, our reanalysis of their Table 1 indicates that it is not implausible that "rzx" is as high as .90. Second, several studies report that selection ratios of .30 or lower are not extreme. Finally, our reanalysis of their Table 5 indicates that Sackett et al. substantially underestimate the severity of RR and its biasing effect on operational validity in concurrent validation studies due to their use of a particular RR correction method (Case IV). We believe these findings suggest that there is not sufficient support for the rationale behind Sackett et al.'s recommendation and, thus, their recommendation itself should be reconsidered. (PsycInfo Database Record (c) 2023 APA, all rights reserved).}, } @article {pmid37487179, year = {2025}, author = {Kotzé, JL and Frazier, PA and Huber, KA and Lust, KA}, title = {Predictors of Sexual Harassment Using Classification and Regression Tree Analyses and Hurdle Models: A Direct Replication.}, journal = {Journal of sex research}, volume = {62}, number = {2}, pages = {165-176}, doi = {10.1080/00224499.2023.2232354}, pmid = {37487179}, issn = {1559-8519}, mesh = {Humans ; *Sexual Harassment/statistics & numerical data ; Female ; Male ; *Students/statistics & numerical data ; Young Adult ; Adolescent ; Universities/statistics & numerical data ; Adult ; *Crime Victims/statistics & numerical data ; *Sexual and Gender Minorities/statistics & numerical data ; Risk Factors ; *Models, Statistical ; }, abstract = {Sexual harassment affects a large percentage of higher education students in the US. A previous study identified several risk factors for sexual harassment using hurdle models and classification and regression tree (CART) analyses. The purpose of the present study was to assess the robustness of these findings by replicating the analyses with a new sample of students. Secondary data analysis was conducted using data from 9,552 students from two- and four-year colleges. Hurdle model coefficients were assessed for replicability based on statistical significance and consistency of the replication effect size relative to the original effect size. Kotzé et al.'s findings were robust, with 91% of all tested effects meeting at least one of two replication criteria in the hurdle models and 88% of the variables replicating in the CARTs. Being younger, consuming alcohol more frequently, attending a four-year college, and having experienced more prior victimization and adversity were important predictors of peer harassment whereas being LGBQ+ was an important predictor of sexual harassment from faculty/staff. These findings can inform targeted prevention and intervention programs. More research is needed to understand why certain demographic and contextual variables are associated with greater harassment risk.}, } @article {pmid37481584, year = {2023}, author = {Yu, X and Capers, PL and Zoh, RS and Allison, DB}, title = {Correcting calculation and data errors reveals that the original conclusions were incorrect in "The best drug supplement for obesity treatment: a systematic review and network meta-analysis".}, journal = {Diabetology & metabolic syndrome}, volume = {15}, number = {1}, pages = {163}, pmid = {37481584}, issn = {1758-5996}, support = {R25 HL124208/HL/NHLBI NIH HHS/United States ; R25HL124208/NH/NIH HHS/United States ; R01DK132385/NH/NIH HHS/United States ; }, abstract = {The goal of this study was to reproduce and evaluate the reliability of the network meta-analysis performed in the article "The best drug supplement for obesity treatment: A systematic review and network meta-analysis" by Salari et al. In recent years, it has become more common to employ network meta-analysis to assess the relative efficacy of treatments often used in clinical practice. To duplicate Salari et al.'s research, we pulled data directly from the original trials and used Cohen's D to determine the effect size for each treatment. We reanalyzed the data since we discovered significant differences between the data we retrieved and the data given by Salari et al. We present new effect size estimates for each therapy and conclude that the prior findings were somewhat erroneous. Our findings highlight the importance of ensuring the accuracy of network meta-analyses to determine the quality and strength of existing evidence.}, } @article {pmid37475658, year = {2023}, author = {Roleston, C and Shaw, R and West, K}, title = {Compassionate communities interventions: a scoping review.}, journal = {Annals of palliative medicine}, volume = {12}, number = {5}, pages = {936-951}, doi = {10.21037/apm-22-867}, pmid = {37475658}, issn = {2224-5839}, mesh = {Humans ; *Palliative Care/methods ; Australia ; Europe ; }, abstract = {BACKGROUND: The compassionate communities (CC) movement is an emergent health promotion approach to palliative care that views illness, dying, death, and loss as universal experiences, and challenges the notion that disease precludes one from health care attention and interest. It seeks to normalise these phenomena and reorientate care to communities by activating naturally occurring networks and mobilising community resources. A surge of interventions aligned with the ethos of CC has been observed over the last decade. This scoping review seeks to synthesise what is currently known about the design, efficacy, and impact of CC interventions.

METHODS: Cochrane, PubMed, Scopus, and Web of Science were systematically searched. Hand searching was performed on three key journals, reference lists and citation lists of included articles, and relevant review articles. Two levels of analysis were conducted. First, a numerical presentation of the characteristics of CC interventions. Second, a thematically orientated narrative analysis of intervention efficacy.

RESULTS: A total of 1,882 records were screened; 62 papers were included. Most were implemented by palliative care organisations in Europe, North America, and Australia. Included studies were mapped against Clark et al.'s taxonomy of end-of-life interventions: educational (n=17); service (n=20); clinical (n=3); cultural (n=4); and multi-dimensional (n=18) interventions are discussed. While preliminary findings are positive, claims of efficacy are limited due to methodological paucity in the field.

CONCLUSIONS: We argue that the field would benefit from more transparent and theoretically driven CC interventions in order to explicate the mechanism(s) for successful intervention implementation.}, } @article {pmid37467728, year = {2023}, author = {Jia, X and Wang, S and Lu, J}, title = {Plasma protein biomarkers trailblaze as early predictors of type 1 diabetes.}, journal = {Cell reports. Medicine}, volume = {4}, number = {7}, pages = {101116}, pmid = {37467728}, issn = {2666-3791}, mesh = {Child ; Humans ; *Diabetes Mellitus, Type 1/diagnosis ; *Islets of Langerhans/metabolism ; Autoimmunity ; Autoantibodies ; Biomarkers ; }, abstract = {Nakayasu et al.'s investigation[1] on children from TEDDY study revealed robust predictive value of plasma protein biomarkers in identifying the emergence of persistent autoantibodies and type 1 diabetes. Remarkably, this predictive accuracy was observed six months prior to autoimmunity initiation.}, } @article {pmid37458245, year = {2023}, author = {Yu, S and Wei, JC}, title = {Regarding Mastorino et al.'s 'Efficacy of anti-IL-23 and anti-IL-17 after adalimumab failure in psoriatic patients'.}, journal = {Journal of the European Academy of Dermatology and Venereology : JEADV}, volume = {37}, number = {12}, pages = {e1388-e1389}, doi = {10.1111/jdv.19334}, pmid = {37458245}, issn = {1468-3083}, mesh = {Humans ; Adalimumab/therapeutic use ; *Arthritis, Psoriatic/drug therapy ; Antibodies, Monoclonal/therapeutic use ; *Antirheumatic Agents/therapeutic use ; *Psoriasis/drug therapy ; Treatment Outcome ; }, } @article {pmid37451603, year = {2024}, author = {Levin, MG and Aragam, KG}, title = {Truncations of Titin and Left Atrial Cardiomyopathy: Comment on Henkens et al.'s article, Left Atrial Function in Patients With Titin Cardiomyopathy.}, journal = {Journal of cardiac failure}, volume = {30}, number = {1}, pages = {61-63}, doi = {10.1016/j.cardfail.2023.06.019}, pmid = {37451603}, issn = {1532-8414}, mesh = {Humans ; Connectin/genetics ; Atrial Function, Left ; *Heart Failure ; *Cardiomyopathies ; Muscle Proteins ; }, } @article {pmid37449983, year = {2023}, author = {Dureux, A and Zanini, A and Selvanayagam, J and Menon, RS and Everling, S}, title = {Gaze patterns and brain activations in humans and marmosets in the Frith-Happé theory-of-mind animation task.}, journal = {eLife}, volume = {12}, number = {}, pages = {}, pmid = {37449983}, issn = {2050-084X}, support = {FRN 148365//CIHR/Canada ; }, mesh = {Humans ; Animals ; *Callithrix ; Brain ; *Theory of Mind ; Cognition ; Movement ; }, abstract = {Theory of Mind (ToM) refers to the cognitive ability to attribute mental states to other individuals. This ability extends even to the attribution of mental states to animations featuring simple geometric shapes, such as the Frith-Happé animations in which two triangles move either purposelessly (Random condition), exhibit purely physical movement (Goal-directed condition), or move as if one triangle is reacting to the other triangle's mental states (ToM condition). While this capacity in humans has been thoroughly established, research on nonhuman primates has yielded inconsistent results. This study explored how marmosets (Callithrix jacchus), a highly social primate species, process Frith-Happé animations by examining gaze patterns and brain activations of marmosets and humans as they observed these animations. We revealed that both marmosets and humans exhibited longer fixations on one of the triangles in ToM animations, compared to other conditions. However, we did not observe the same pattern of longer overall fixation duration on the ToM animations in marmosets as identified in humans. Furthermore, our findings reveal that both species activated extensive and comparable brain networks when viewing ToM versus Random animations, suggesting that marmosets differentiate between these scenarios similarly to humans. While marmosets did not mimic human overall fixation patterns, their gaze behavior and neural activations indicate a distinction between ToM and non-ToM scenarios. This study expands our understanding of nonhuman primate cognitive abilities, shedding light on potential similarities and differences in ToM processing between marmosets and humans.}, } @article {pmid37431925, year = {2024}, author = {Atay, EJ and Murry, AT and Barnabe, C and Sawyer, O and Bednar, MA}, title = {Indigenous Mentorship for the Health Sciences: An Appraisal of a Contemporary Model by Indigenous Stakeholders.}, journal = {Teaching and learning in medicine}, volume = {36}, number = {5}, pages = {637-653}, doi = {10.1080/10401334.2023.2230577}, pmid = {37431925}, issn = {1532-8015}, mesh = {Humans ; *Mentors ; Female ; Male ; Qualitative Research ; Mentoring ; Adult ; Interviews as Topic ; }, abstract = {Construct: In 2021, Murry et al. put forward a model of Indigenous mentorship within the health sciences based on the behaviors of Indigenous mentors toward their Indigenous mentees. This study explored mentees' endorsements and/or criticisms of the IM model and how IM constructs and behaviors described in the model benefited them. Background: Models of Indigenous mentorship have been developed previously yet have not yet been empirically examined, restricting our ability to measure or make claims as to their consequences, correlates, and antecedents. Approach: Interviews with six Indigenous mentees asked about their: 1) resonance with the model, 2) stories related to mentors' behaviors, 3) perceived benefits of their mentors' behaviors on their journey, and 4) components they felt were missing from the model. Data were analyzed using qualitative content analysis. Findings: Overall, the model resonated with participants. Mentees told stories about mentors engaging in the IM constructs practicing relationalism most frequently, followed by fostering Indigenous identity development, utilizing a mentee-centered focus, and imbuing criticality, advocacy, and abiding by Indigenous ethics. Benefits included improved career and work attitudes, motivation, and overall well-being, engaging in helping behaviors, and enhanced criticality. Recommendations to expand the model included incorporating: 1) additional mentor behaviors (e.g., transference of traditional knowledge), 2) higher-order dimensions (e.g., the impact of the institution), 3) specific mentee characteristics (e.g., age and gender), and 4) additional types of mentoring relationships (e.g., peer, multiple mentors). Conclusions: This study showed that Murry et al.'s model resonated with primary stakeholders (i.e., Indigenous mentees), that Indigenous mentorship behaviors have perceived consequences that are important for adjustment, and ways the model is limited or mis-specified. This information can inform mentor practices, selection and support, and program evaluation.}, } @article {pmid37431780, year = {2023}, author = {Potente, C and Chumbley, J and Xu, W and Levitt, B and Cole, SW and Ravi, S and Bodelet, JS and Gaydosh, L and Harris, KM and Shanahan, MJ}, title = {Socioeconomic Inequalities and Molecular Risk for Aging in Young Adulthood.}, journal = {American journal of epidemiology}, volume = {192}, number = {12}, pages = {1981-1990}, pmid = {37431780}, issn = {1476-6256}, support = {P01 HD031921/HD/NICHD NIH HHS/United States ; R01 AG043404/AG/NIA NIH HHS/United States ; P30 AG017265/AG/NIA NIH HHS/United States ; R01 AG033590/AG/NIA NIH HHS/United States ; P2C HD050924/HD/NICHD NIH HHS/United States ; R01 HD087061/HD/NICHD NIH HHS/United States ; }, mesh = {Adult ; Adolescent ; Humans ; Young Adult ; Longitudinal Studies ; *Social Class ; *Aging/genetics ; Smoking ; Income ; Socioeconomic Factors ; }, abstract = {Diverse manifestations of biological aging often reflect disparities in socioeconomic status (SES). In this paper, we examine associations between indicators of SES and an mRNA-based aging signature during young adulthood, before clinical indications of aging are common. We use data from wave V (2016-2018) of the National Longitudinal Study of Adolescent to Adult Health, a nationally representative study of adults aged 33-43 years, with transcriptomic data from a subset of 2,491 participants. Biological aging is measured using 1) a composite transcriptomic aging signature previously identified by Peters et al.'s out-of-sample meta-analysis (Nat Commun. 2015;6:8570) and 2) 9 subsets that represent functional pathways of coexpressed genes. SES refers to income, education, occupation, subjective social status, and a composite measure combining these 4 dimensions. We examine hypothesized mechanisms through which SES could affect aging: body mass index, smoking, health insurance status, difficulty paying bills, and psychosocial stress. We find that SES-especially the composite measure and income-is associated with transcriptomic aging and immune, mitochondrial, ribosomal, lysosomal, and proteomal pathways. Counterfactual mediational models suggest that the mediators partially account for these associations. The results thus reveal that numerous biological pathways associated with aging are already linked to SES in young adulthood.}, } @article {pmid37430249, year = {2023}, author = {Linden-Lahti, C and Takala, A and Holmström, AR and Airaksinen, M}, title = {Applicability of drug-related problem (DRP) classification system for classifying severe medication errors.}, journal = {BMC health services research}, volume = {23}, number = {1}, pages = {743}, pmid = {37430249}, issn = {1472-6963}, mesh = {Humans ; Retrospective Studies ; *Document Analysis ; *Group Processes ; Health Facilities ; Medication Errors ; }, abstract = {BACKGROUND: Several classification systems for medication errors (MEs) have been established over time, but none of them apply optimally for classifying severe MEs. In severe MEs, recognizing the causes of the error is essential for error prevention and risk management. Therefore, this study focuses on exploring the applicability of a cause-based DRP classification system for classifying severe MEs and their causes.

METHODS: This was a retrospective document analysis study on medication-related complaints and authoritative statements investigated by the Finnish National Supervisory Authority for Welfare and Health (Valvira) in 2013-2017. The data was classified by applying a previously developed aggregated DRP classification system by Basger et al. Error setting and harm to the patient were identified using qualitative content analysis to describe the characteristics of the MEs in the data. The systems approach to human error, error prevention, and risk management was used as a theoretical framework.

RESULTS: Fifty-eight of the complaints and authoritative statements concerned MEs, which had occurred in a wide range of social and healthcare settings. More than half of the ME cases (52%, n = 30) had caused the patient's death or severe harm. In total, 100 MEs were identified from the ME case reports. In 53% (n = 31) of the cases, more than one ME was identified, and the mean number of MEs identified was 1.7 per case. It was possible to classify all MEs according to aggregated DRP system, and only a small proportion (8%, n = 8) were classified in the category "Other," indicating that the cause of the ME could not be classified to specific cause-based category. MEs in the "Other" category included dispensing errors, documenting errors, prescribing error, and a near miss.

CONCLUSIONS: Our study provides promising preliminary results for using DRP classification system for classifying and analyzing especially severe MEs. With Basger et al.'s aggregated DRP classification system, we were able to categorize both the ME and its cause. More research is encouraged with other ME incident data from different reporting systems to confirm our results.}, } @article {pmid37428923, year = {2023}, author = {Yang, Q and Zhang, W and Liu, S and Gong, W and Han, Y and Lu, J and Jiang, D and Nie, J and Lyu, X and Liu, R and Jiao, M and Qu, C and Zhang, M and Sun, Y and Zhou, X and Zhang, Q}, title = {Unraveling controversies over civic honesty measurement: An extended field replication in China.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {120}, number = {29}, pages = {e2213824120}, pmid = {37428923}, issn = {1091-6490}, mesh = {Humans ; *Individuality ; China ; }, abstract = {Cohn et al. (2019) conducted a wallet drop experiment in 40 countries to measure "civic honesty around the globe," which has received worldwide attention but also sparked controversies over using the email response rate as the sole metric of civic honesty. Relying on the lone measurement may overlook cultural differences in behaviors that demonstrate civic honesty. To investigate this issue, we conducted an extended replication study in China, utilizing email response and wallet recovery to assess civic honesty. We found a significantly higher level of civic honesty in China, as measured by the wallet recovery rate, than reported in the original study, while email response rates remained similar. To resolve the divergent results, we introduce a cultural dimension, individualism versus collectivism, to study civic honesty across diverse cultures. We hypothesize that cultural differences in individualism and collectivism could influence how individuals prioritize actions when handling a lost wallet, such as contacting the wallet owner or safeguarding the wallet. In reanalyzing Cohn et al.'s data, we found that email response rates were inversely related to collectivism indices at the country level. However, our replication study in China demonstrated that the likelihood of wallet recovery was positively correlated with collectivism indicators at the provincial level. Consequently, relying solely on email response rates to gauge civic honesty in cross-country comparisons may neglect the vital individualism versus collectivism dimension. Our study not only helps reconcile the controversy surrounding Cohn et al.'s influential field experiment but also furnishes a fresh cultural perspective to evaluate civic honesty.}, } @article {pmid37423096, year = {2023}, author = {Goodhines, PA and Rathod, K}, title = {Substance use and sleep health in young adults: Implications for integrated treatment and harm reduction.}, journal = {Sleep medicine reviews}, volume = {70}, number = {}, pages = {101811}, doi = {10.1016/j.smrv.2023.101811}, pmid = {37423096}, issn = {1532-2955}, mesh = {Humans ; Young Adult ; *Harm Reduction ; Sleep ; *Substance-Related Disorders/therapy ; Systematic Reviews as Topic ; Meta-Analysis as Topic ; }, abstract = {In their systematic review and meta-analysis, Meneo and colleagues document distinct substance-sleep effects reported by young adults (ages 18-30) across multidimensional sleep health and different substances used in the naturalistic environment, including alarming rates of self-medication for sleep aid. Key innovations of Meneo et al.'s review include (a) a multidimensional approach to defining sleep health and (b) robust inclusion of various substances commonly used in young adults. Although future research will be essential to clarifying transdiagnostic risk mechanisms, interplay of co-used substances, and the role of expectancies in risk processes, the developing literature reviewed herein may inform much-needed clinical recommendations. This work by Meneo et al should prompt an emphasis on approaching young adult substance use and self-medication through a harm reduction lens, highlighting recommendations for integrated behavioral sleep treatment tailored to stage of change using motivational interviewing.}, } @article {pmid37420428, year = {2022}, author = {Yang, CW and Lin, J and Tsai, CW and Cheng, CL}, title = {Cryptanalysis of a Semi-Quantum Bi-Signature Scheme Based on W States.}, journal = {Entropy (Basel, Switzerland)}, volume = {24}, number = {10}, pages = {}, pmid = {37420428}, issn = {1099-4300}, support = {NSTC 111-2221-E-039-014, NSTC 110-2221-E-143-003, NSTC 110-2221-E-259-001, NSTC 110-2221-E-143-004, NSTC 110-2222-E-005-006, NSTC 110-2634-F-005-006, NSTC 111-2218-E-005-007-MBK, NSTC 111-2221-E-005-048, and NSTC 111-2221-E-025-010//National Science and Technology Council, Taiwan, R.O.C./ ; CMU110-S-21 and CMU111-MF-112//China Medical University, Taiwan/ ; }, abstract = {Recently, Zhao et al. proposed a semi-quantum bi-signature (SQBS) scheme based on W states with two quantum signers and just one classical verifier. In this study, we highlight three security issues with Zhao et al.'s SQBS scheme. In Zhao et al.'s SQBS protocol, an insider attacker can perform an impersonation attack in the verification phase and an impersonation attack in the signature phase to capture the private key. In addition, an eavesdropper can perform a man-in-the-middle attack to obtain all of the signer's secret information. All of the above three attacks can pass the eavesdropping check. Without considering these security issues, the SQBS protocol could fail to ensure the signer's secret information.}, } @article {pmid37416830, year = {2023}, author = {Bartoš, F and Maier, M and Shanks, DR and Stanley, TD and Sladekova, M and Wagenmakers, EJ}, title = {Meta-analyses in psychology often overestimate evidence for and size of effects.}, journal = {Royal Society open science}, volume = {10}, number = {7}, pages = {230224}, pmid = {37416830}, issn = {2054-5703}, abstract = {Adjusting for publication bias is essential when drawing meta-analytic inferences. However, most methods that adjust for publication bias do not perform well across a range of research conditions, such as the degree of heterogeneity in effect sizes across studies. Sladekova et al. 2022 (Estimating the change in meta-analytic effect size estimates after the application of publication bias adjustment methods. Psychol. Methods) tried to circumvent this complication by selecting the methods that are most appropriate for a given set of conditions, and concluded that publication bias on average causes only minimal over-estimation of effect sizes in psychology. However, this approach suffers from a 'Catch-22' problem-to know the underlying research conditions, one needs to have adjusted for publication bias correctly, but to correctly adjust for publication bias, one needs to know the underlying research conditions. To alleviate this problem, we conduct an alternative analysis, robust Bayesian meta-analysis (RoBMA), which is not based on model-selection but on model-averaging. In RoBMA, models that predict the observed results better are given correspondingly larger weights. A RoBMA reanalysis of Sladekova et al.'s dataset reveals that more than 60% of meta-analyses in psychology notably overestimate the evidence for the presence of the meta-analytic effect and more than 50% overestimate its magnitude.}, } @article {pmid37401352, year = {2024}, author = {Vancappel, A and Hingray, C and Reveillere, C and El-Hage, W}, title = {Disentangling the Link Between Mindfulness and Dissociation in PTSD: The Mediating Role of Attention and Emotional Acceptance.}, journal = {Journal of trauma & dissociation : the official journal of the International Society for the Study of Dissociation (ISSD)}, volume = {25}, number = {1}, pages = {30-44}, doi = {10.1080/15299732.2023.2231907}, pmid = {37401352}, issn = {1529-9740}, mesh = {Humans ; Female ; *Stress Disorders, Post-Traumatic/psychology ; *Mindfulness ; Emotions ; Attention ; *Emotional Regulation ; }, abstract = {INTRODUCTION: A number of studies have investigated the relationship between mindfulness and dissociation and suggested that mindfulness-based interventions could be effective in the treatment of dissociative symptoms. A recent study in healthy volunteers found that attention and emotional acceptance mediates this relationship. However, no study has yet been performed among a clinical sample to assess this association.

METHOD: We recruited 90 patients (76 women) suffering from Posttraumatic Stress Disorder (PTSD). They completed self-report questionnaires to measure PTSD, dissociation, emotion regulation difficulties, childhood trauma, mindfulness abilities and cognitive abilities.

RESULTS: We found that mindfulness abilities, emotional difficulties, dissociation and attention-concentration were all related to each other. Using a step-by-step approach and bootstrapping techniques, we found a significant indirect effect of mindfulness abilities on dissociation through non-acceptance (confidence interval 95%=-.14 to -.01) and attentional difficulties (confidence interval 95%=-.23 to -.05).

CONCLUSION: Patients with higher levels of dissociative symptoms have less capacity for mindfulness. Our results support Bishop et al.'s model proposing that attention and emotional acceptance are the two active components of mindfulness. To extend our findings, clinical trials are required to evaluate a causal relationship and the effectiveness of mindfulness-based interventions for patients suffering from dissociation.}, } @article {pmid37400014, year = {2023}, author = {Venanzi, MS and Martini, G and Rossi, A and Piatelli, G and Pavanello, M}, title = {Intrasacral meningoceles: Clinical presentation, surgical management, and postoperative outcome: The Giannina Gaslini Hospital's experience.}, journal = {Neuro-Chirurgie}, volume = {69}, number = {5}, pages = {101466}, doi = {10.1016/j.neuchi.2023.101466}, pmid = {37400014}, issn = {1773-0619}, mesh = {Humans ; Adult ; *Meningocele/diagnosis/surgery ; Retrospective Studies ; Laminectomy ; *Cysts/surgery ; Endoscopy ; *Arachnoid Cysts/surgery ; }, abstract = {INTRODUCTION: Intrasacral meningoceles are cysts associated with herniating arachnoid with no nerve root within due to an area of weakness of the dura mater. They are thought to be congenital, but they are usually not symptomatic until adulthood. Surgical treatment is generally indicated in the presence of symptoms.

METHODS: We selected cases belonging to the IB category of Nabors et al.'s classification who underwent surgery between 2008 and 2021 at Giannina Gaslini Hospital. Exclusion criteria were prior history of trauma, infections, or operations. Patients' clinical details, associated conditions, surgical techniques, peri- and postoperative complications, and outcomes were collected retrospectively from clinical charts. We compared our series to literature: keywords "intrasacral meningocele" were used on the search engine MEDLINE - Pubmed.

RESULTS: We identified 23 cases: 5 of the 14 symptomatic patients had a complete resolution, and 5 had a substantial clinical improvement after surgery. Cyst recurrence and major postoperative complication occurred in none. Among 59 articles considered for evaluation, 50 were excluded and remaining 9 articles underwent full-text analysis.

DISCUSSION AND CONCLUSION: The pathogenesis of instrasacral meningoceles is still not completely understood and the spectrum of symptoms is wide. A posterior surgical approach with sacral laminectomy is preferred, although in selected cases it is possible to perform a supplemental anterior approach (sometimes endoscopic). In our surgical series, the largest one published in the literature, a good clinical outcome was achieved in most patients with no cyst's recurrence, pointing out the importance of surgical interruption of communication between cyst and subdural space.}, } @article {pmid37394876, year = {2023}, author = {Brown, H and De'Ambrosis, B and Yong-Gee, S and Muir, J}, title = {Reply to: Adler et al.'s Melanoma diagnosis at a specialist dermatology practice without the use of photographic surveillance.}, journal = {The Australasian journal of dermatology}, volume = {64}, number = {4}, pages = {e399-e400}, doi = {10.1111/ajd.14124}, pmid = {37394876}, issn = {1440-0960}, mesh = {Humans ; *Dermatology ; *Melanoma/diagnosis ; *Skin Neoplasms/diagnosis ; Photography ; Dermoscopy ; }, } @article {pmid37380975, year = {2023}, author = {Salehi, N and Afrashteh, MY and Majzoobi, MR and Ziapour, A and Janjani, P and Karami, S}, title = {Does coping with pain help the elderly with cardiovascular disease? The association of sense of coherence, spiritual well-being and self-compassion with quality of life through the mediating role of pain self-efficacy.}, journal = {BMC geriatrics}, volume = {23}, number = {1}, pages = {393}, pmid = {37380975}, issn = {1471-2318}, mesh = {Aged ; Male ; Female ; Humans ; *Sense of Coherence ; Quality of Life ; *Cardiovascular Diseases/diagnosis/epidemiology/therapy ; Iran ; Self Efficacy ; Self-Compassion ; Adaptation, Psychological ; Pain/epidemiology ; }, abstract = {BACKGROUND: Population ageing is considered one of the biggest challenges facing the world, and the status of the elderly in society and their quality of life (QOL) have proved to be a concern in professional and scientific research circles. As a result, the current study sought to investigate the role of pain self-efficacy (PSE) as a moderator in the relationship between sense of coherence (SOC), spiritual well-being, and self-compassion with QOL in Iranian elderly with cardiovascular disease (CVD).

METHOD: This was a correlational study of the path analysis type. The statistical population included all elderly people with CVD who were at least 60 years of age in Kermanshah Province, Iran, in 2022, of whom 298 (181 men and 117 women) were selected using convenience sampling and according to the inclusion and exclusion criteria. The participants answered questionnaires from the World Health Organization on QOL, Paloutzian and Ellison's spiritual well-being, Nicholas's PSE, Antonovsky's SOC, and Raes et al.'s self-compassion.

RESULTS: The results of path analysis demonstrated that the hypothesized model of this study has a good fit in the studied sample. There were significant paths between SOC (β = 0.39), spiritual well-being (β = 0.13) and self-compassion (β = 0.44) with PSE. Although there were significant paths between SOC (β = 0.16) and self-compassion (β = 0.31) with QOL, there was no significant path between spiritual well-being and QOL (β = 0.06). Besides, there was a significant path between PSE and QOL (β = 0.35). Finally, PSE was found to mediate the relationship of SOC, spiritual well-being and self-compassion with QOL.

CONCLUSION: The results may provide psychotherapists and counselors working in this field of inquiry with advantageous information to choose or create a useful therapeutic method to work with the elderly with CVD. Meanwhile, other researchers are suggested to examine other variables which may serve a mediating role in the mentioned model.}, } @article {pmid37374567, year = {2023}, author = {Shah, AW and Ha, SH and Siddique, JA and Kim, BH and Yoon, YO and Lim, HK and Kim, SK}, title = {Investigating the Influence of Mg Content Variations on Microstructures, Heat-Treatment, and Mechanical Properties of Al-Cu-Mg Alloys.}, journal = {Materials (Basel, Switzerland)}, volume = {16}, number = {12}, pages = {}, pmid = {37374567}, issn = {1996-1944}, support = {20011420//Ministry of Trade, Industry and Energy South Korea/ ; }, abstract = {The objective of this study was to examine the impact of varying magnesium levels in the α-Al + S + T region of the Al-Cu-Mg ternary phase diagram on the solidification process, microstructure development, tensile properties, and precipitation hardening of Al-Cu-Mg-Ti alloys. The outcomes indicate that alloys with 3% and 5% Mg solidified with the formation of binary eutectic α-Al-Al2CuMg (S) phases, whereas in the alloy with 7% Mg, the solidification process ended with the formation of eutectic α-Al-Mg32(Al, Cu)49 (T) phases. Additionally, a significant number of T precipitates were noticed inside the granular α-Al grains in all alloys. In the as-cast condition, the 5% Mg-added alloy showed the best combination of yield strength (153 MPa) and elongation (2.5%). Upon T6 heat treatment, both tensile strength and elongation increased. The 7% Mg-added alloy had the best results, with a yield strength of 193 MPa and an elongation of 3.4%. DSC analysis revealed that the increased tensile strength observed after the aging treatment was associated with the formation of solute clusters and S″/S' phases.}, } @article {pmid37365747, year = {2023}, author = {Lavigne, KN and Grawitch, MJ}, title = {Work-life conflict and facilitation: Mostly indirect effects on domain-specific and work-life balance satisfaction over time.}, journal = {International journal of psychology : Journal international de psychologie}, volume = {58}, number = {6}, pages = {526-535}, doi = {10.1002/ijop.12927}, pmid = {37365747}, issn = {1464-066X}, mesh = {Humans ; *Work-Life Balance ; Cross-Sectional Studies ; Longitudinal Studies ; *Personal Satisfaction ; Job Satisfaction ; Surveys and Questionnaires ; }, abstract = {The majority of work-life research has been anchored around work-life conflict/facilitation and balance constructs, though these constructs have largely been examined in isolation from one another. The purpose of the current study is to provide a direct replication and longitudinal extension of Grawitch et al.'s cross-sectional study exploring work-life balance satisfaction's relation to interdomain conflict and facilitation. We conducted a three-wave longitudinal study (0, 1 and 6 months) to test the causal assumptions of the original study. In addition to exploring relationships between bidirectional conflict/facilitation and work-non-work balance (WLB) satisfaction variables, the pathways by which work-life constructs influence work and non-work life satisfaction were examined. Time 1 results largely replicated those from Grawitch et al. Time 2 and Time 3 models demonstrated consistency in the relationships between satisfaction with work and non-work life and work-life balance and general stability across time points. Work-life conflict and life-work facilitation demonstrated the strongest indirect effects from Time 1 to Time 3 satisfaction constructs. Theoretical and practical implications are discussed in light of these findings.}, } @article {pmid37363649, year = {2023}, author = {Zhi, H and Fienup, DM and Greer, RD and Henderson, SS}, title = {A Comparison of Stimulus Set Sizes: Systematic Replication with Operant Analysis Acquisition Criteria.}, journal = {Behavior analysis in practice}, volume = {16}, number = {4}, pages = {1-13}, pmid = {37363649}, issn = {1998-1929}, abstract = {We conducted a systematic replication of Kodak et al.'s Journal of Applied Behavior Analysis, 53(1), 265-283 (2020) and Vladescu et al.'s Behavior Analysis in Practice, 14(1), 193-197 (2021) experiments on the effects of stimulus set sizes on skill acquisition. The researchers manipulated the stimulus set sizes by teaching 3, 6, and 12 sight words simultaneously during learn unit instruction. Researchers taught participants until the participant's responding reached the acquisition criterion for 12 different sight words per set size condition. The acquisition criterion was set for an individual operant, whereby when accuracy met criterion for a single sight word, that sight word was replaced in the following session. The results showed that the set-size-3 was more efficient in producing criterion-level responding during acquisition than the set-size-6, and -12, which was consistent with Vladescu et al.'s findings. However, the set-size-12 reliably produced the highest maintenance levels for all participants. The definition of "effectiveness" based on acquisition or maintenance was discussed.}, } @article {pmid37362759, year = {2023}, author = {Jonbekova, D}, title = {Government scholarships for international higher education: pathways for social change in Kazakhstan.}, journal = {Higher education}, volume = {}, number = {}, pages = {1-17}, pmid = {37362759}, issn = {1573-174X}, abstract = {Globally, scholarships for international higher education play a critical role in human capital development. While substantial research has documented the benefits such scholarships provide for individuals, their impact on the creation of pathways for social change remains under-researched. This paper bridges this gap by examining the extent to which a government scholarship for international education has created pathways for social change in Kazakhstan. Data were collected through interviews with 67 scholarship alumni. Drawing on Dassin et al.'s (2018) framework for pathways to social change, the findings reveal that international education fosters social change in Kazakhstan in four ways. First, the scholarship program develops local talent and builds agents of change. Second, it widens access to international education, particularly for individuals from marginalized communities, who would otherwise lack access owing to their scarce financial resources. Third, the program develops alumni's cosmopolitan and intercultural competencies and strengthens international collaborations. Finally, it creates associations and groups through which alumni can collectively contribute to society. The findings highlight that while the interviewed alumni foster strong patriotic feelings and are determined to contribute to the prosperity of their country, underdeveloped industries, economic volatility, and top-down bureaucracy in workplaces limit their potential contributions to social changes. These findings may help policymakers and administrators to reconsider and improve on the design and structure of scholarship programs.}, } @article {pmid37358995, year = {2023}, author = {Sun, L and Wei, X and Wang, K and Zhou, J}, title = {Research trends from 1992 to 2022 of acupuncture anesthesia: a bibliometric analysis.}, journal = {Frontiers in medicine}, volume = {10}, number = {}, pages = {1194005}, pmid = {37358995}, issn = {2296-858X}, abstract = {BACKGROUND: Acupuncture anesthesia is a significant technical development that originated in China in 1958 and was introduced to the West in the early 1970s. Due to its relative novelty, it has been the subject of intense scrutiny and contestation. Since the early 1970s, the use of acupuncture as a complementary treatment for opioid analgesics has been accepted. Research on acupuncture anesthesia has helped to reduce clinical opioid abuse. However, only a few articles have focused on previous publications that reflect the trend of the study, the main investigators, reciprocal collaboration, and other information in this field. In view of this, we utilized bibliographic analysis methods to objectively analyze current trends and research hotspots in this field, aiming to provide a foundation and reference for future studies.

METHODS: The Web of Science database was searched for publications related to acupuncture anesthesia between 1992 and 2022. The CiteSpace and VOSviewer were used to analyze the annual publications, authors, Co-cited authors, and their countries (regions) and institutions, co-occurrence keywords, burst keywords, Co-citation references and Co-citation journals.

RESULTS: A total of 746 eligible publications were retrieved from the database for the analysis, including 637 articles and 109 reviews. And the trend of annual publications continued to grow. Aashish J. Kumar, Daniel I. Sessler, Baoguo Wang, and Paul F. White published the most papers in this field (7), and all authors, had a very low centrality (<0.01). China (252) and the University of California System (21) were the most productive country (region) and institution, respectively, while the United States (0.62) and University of California System (0.16) had the highest centrality. After removing keywords related to the search strategy, the three most frequent were pain (115), electroacupuncture (109), and stimulation (91). The six most recent burst keywords were recovery, transcutaneous electrical acupoint stimulation, systematic review, quality, general anesthesia, and surgery. Wang et al.'s article had the highest co-citation count (20), whereas Zhang et al.'s articles had the highest centrality (0.25). The Journal of Anesthesia and Analgesia was the most influential one (408 co-citations).

CONCLUSION: This research provides valuable information for the study of acupuncture anesthesia. In recent years, frontier topics in acupuncture anesthesia research have been the promotion of perioperative rehabilitation, anesthesia management, and quality improvement.}, } @article {pmid37358532, year = {2023}, author = {Verona, E and Joyner, K}, title = {What is this measuring? Comment on Gatner et al. (2022).}, journal = {Personality disorders}, volume = {14}, number = {4}, pages = {401-404}, doi = {10.1037/per0000614}, pmid = {37358532}, issn = {1949-2723}, mesh = {Humans ; *Antisocial Personality Disorder ; *Crime ; Canada ; }, abstract = {In their crime cost estimation, Gatner et al. (2022) conclude that psychopathic personality disorder (PPD) is associated with billions of dollars of crime costs in the United States (US) and Canada. Gatner et al.'s analysis goes far in putting a cost estimate to PPD, when the burden of psychopathy for the criminal justice system has been unspecified for years. Nonetheless, in the present commentary, we identify two broad problems with their analyses that motivate caution in the interpretation of the findings and their potential applicability: (a) the conceptualization of psychopathy that formed the bases for estimates of PPD, and (b) the assumptions underlying crime cost estimates made by Gatner et al. The questionable assumptions and diminished focus on the criminal justice context in the US versus Canada limit the extent to which these estimates can produce useful policy implications and may instead perpetuate misconceptions of crime and PPD. (PsycInfo Database Record (c) 2023 APA, all rights reserved).}, } @article {pmid37356271, year = {2023}, author = {Sánchez-Dorado, J}, title = {Creativity, pursuit and epistemic tradition.}, journal = {Studies in history and philosophy of science}, volume = {100}, number = {}, pages = {81-89}, doi = {10.1016/j.shpsa.2023.05.003}, pmid = {37356271}, issn = {0039-3681}, mesh = {Phylogeny ; Prospective Studies ; *Creativity ; *Philosophy/history ; Paleontology ; }, abstract = {This paper revisits the standard definition of scientific creativity in the contemporary philosophical literature. The standard definition of creativity says that there are two necessary, and jointly sufficient, conditions for creativity, novelty and value. This paper proposes to characterize the value condition of creativity in terms of "pursuitworthiness". The notion of pursuitworthiness, adopted from the recent debate on scientific pursuit in philosophy of science, refers to a form of prospective epistemic worth. It indicates that a certain object (such as a scientific hypothesis) is promising or has the potential to be epistemically fertile in the future, if further investigated. To support the claim that creative scientific instances are, qua creative, valuable in the sense of pursuitworthy, three examples of creative hypotheses taken from the history of the geosciences are introduced: MacCulloch's continuity hypothesis in mid-19th-century geology, Baron et al.'s phylogenetic hypothesis in contemporary paleontology, and the widely discussed Anthropocene hypothesis.}, } @article {pmid37347372, year = {2023}, author = {Adidharma, P and Prasetya, M and Wardhana, AW and Inoue, T and Sulistyanto, A and Fadhil, and Oswari, S and Keswani, RR and Kusdiansah, M and Aji, YK and Ramadhan, R and Arham, A}, title = {Analyzing the cost-effectiveness of microvascular decompression and percutaneous radiofrequency rhizotomy for trigeminal neuralgia: the role of clinical classification.}, journal = {Neurosurgical review}, volume = {46}, number = {1}, pages = {144}, pmid = {37347372}, issn = {1437-2320}, mesh = {Humans ; *Microvascular Decompression Surgery ; *Trigeminal Neuralgia/surgery ; Cost-Benefit Analysis ; Treatment Outcome ; Rhizotomy ; Prospective Studies ; Retrospective Studies ; *Radiosurgery ; }, abstract = {Trigeminal neuralgia (TN) is a neuropathic pain that can be treated with microvascular decompression (MVD) or percutaneous radiofrequency rhizotomy (PRR) when medications fail. However, the cost-effectiveness of these interventions is uncertain, and it is unclear whether TN should be considered as a single entity for cost-effectiveness analysis. To address these issues, a prospective cohort study was conducted between 2017 and 2020, documenting Burchiel et al.'s clinical classification, pain-free survival, complications, and costs. Two models of quality-adjusted life years (QALYs) were calculated: pain-specific (PQALY) and pain-complication-specific (PCQALY), based on pain-free survival and complications data, followed by cost-effectiveness analysis. The study included 112 patients, of whom 70 underwent MVD and 42 underwent PRR. Our findings revealed that MVD was less cost-effective in the PCQALY model than PRR, but more cost-effective in the PQALY model and had an incremental cost-effectiveness ratio (ICER) that met the World Health Organization cost-effectiveness threshold in both models. Further clinical classification analysis showed that MVD was only cost-effective in type 1 TN patients, with an ICER of 0.9 and 1.3 times the GDP/capita, based on PQALY and PCQALY, respectively, meeting the cost-effectiveness criteria. Conversely, MVD was economically dominated by PRR for type 2 TN patients based on PQALY. These findings indicate that PRR may be more cost-effective for type 2 TN patients, while MVD remains the cost-effective option for type 1 TN patients. Our study highlights the importance of clinical classification and complication in determining the cost-effectiveness of MVD and PRR for refractory TN.}, } @article {pmid37346720, year = {2023}, author = {Wang, X and Huang, J and Qi, C and Peng, Y and Zhang, S}, title = {An anti-collusion attack defense method for physical layer key generation scheme based on transmission delay.}, journal = {PeerJ. Computer science}, volume = {9}, number = {}, pages = {e1349}, pmid = {37346720}, issn = {2376-5992}, abstract = {Physical layer security (PLS) is considered one of the most promising solutions to solve the security problems of massive Internet of Things (IoTs) devices because of its lightweight and high efficiency. Significantly, the recent physical layer key generation (PLKG) scheme based on transmission delay proposed by Huang et al. (2021) does not have any restrictions on communication methods and can extend the traditional physical layer security based on wireless channels to the whole Internet scene. However, the secret-sharing strategy adopted in this scheme has hidden dangers of collusion attack, which may lead to security problems such as information tampering and privacy disclosure. By establishing a probability model, this article quantitatively analyzes the relationship between the number of malicious collusion nodes and the probability of key exposure, which proves the existence of this security problem. In order to solve the problem of collusion attack in Huang et al.'s scheme, this article proposes an anti-collusion attack defense method, which minimizes the influence of collusion attack on key security by optimizing parameters including the number of the middle forwarding nodes, the random forwarding times, the time delay measurement times and the out-of-control rate of forwarding nodes. Finally, based on the game model, we prove that the defense method proposed in this article can reduce the risk of key leakage to zero under the scenario of the "Careless Defender" and "Cautious Defender" respectively.}, } @article {pmid37343539, year = {2023}, author = {Kallhoff, L and Moua, PT and Salomon, D and Wambaugh, J}, title = {The Outcomes of Remote Administration of Combined Aphasia and Apraxia of Speech Treatment: A Single-Subject Experimental Design Study.}, journal = {American journal of speech-language pathology}, volume = {32}, number = {5S}, pages = {2402-2417}, doi = {10.1044/2023_AJSLP-22-00297}, pmid = {37343539}, issn = {1558-9110}, mesh = {Humans ; *Aphasia/therapy/complications ; *Apraxias/diagnosis/therapy/complications ; Research Design ; Speech ; Speech Therapy/methods ; Treatment Outcome ; }, abstract = {PURPOSE: This study was designed to examine the outcomes of Combined Aphasia and Apraxia of Speech Treatment (CAAST) administered remotely in terms of acquisition and generalization effects and to compare these effects to previous in-person CAAST studies and Response Elaboration Training (RET)/Modified-Response Elaboration Training (M-RET) benchmarks.

METHOD: Multiple probe designs across participants and behaviors were employed with three speakers with chronic aphasia and apraxia of speech. Correct information units (CIUs) were the primary outcome measure to measure changes in language production. Percent consonants correct (PCC) was used as the secondary outcome measure to evaluate changes in speech sound accuracy. Production of CIUs was compared with existing benchmarks from Bunker et al.'s (2019) meta-analysis of previous RET/M-RET studies. In addition, both CIUs and PCC were compared with the most recent CAAST in-person studies.

RESULTS: All participants demonstrated substantial increases in CIUs for treated and untreated picture sets, comparable to outcomes of in-person CAAST administration. These language changes were maintained at posttreatment intervals for all participants. PCC also improved for all participants, with gains in articulatory accuracy being maintained posttreatment.

CONCLUSIONS: Improvements in CIU production and PCC for all three participants were in keeping with results from Wambaugh et al. (2017). These findings provide additional support for the efficacy of CAAST and indicate that remote administration may be a viable alternative to in-person application.

SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.23418635.}, } @article {pmid37341649, year = {2024}, author = {Yu, C and Wang, L and Xu, G and Chen, G and Sang, Q and Wuyun, Q and Wang, Z and Tian, C and Zhang, N}, title = {Comparison of various prediction models in the effect of laparoscopic sleeve gastrectomy on type 2 diabetes mellitus in the Chinese population 5 years after surgery.}, journal = {Chinese medical journal}, volume = {137}, number = {3}, pages = {320-328}, pmid = {37341649}, issn = {2542-5641}, mesh = {Male ; Humans ; Adult ; Female ; Treatment Outcome ; *Diabetes Mellitus, Type 2/surgery ; Retrospective Studies ; *Laparoscopy/methods ; Gastrectomy/methods ; Weight Loss ; Body Mass Index ; *Obesity, Morbid ; }, abstract = {BACKGROUND: The effect of bariatric surgery on type 2 diabetes mellitus (T2DM) control can be assessed based on predictive models of T2DM remission. Various models have been externally verified internationally. However, long-term validated results after laparoscopic sleeve gastrectomy (LSG) surgery are lacking. The best model for the Chinese population is also unknown.

METHODS: We retrospectively analyzed Chinese population data 5 years after LSG at Beijing Shijitan Hospital in China between March 2009 and December 2016. The independent t -test, Mann-Whitney U test, and chi-squared test were used to compare characteristics between T2DM remission and non-remission groups. We evaluated the predictive efficacy of each model for long-term T2DM remission after LSG by calculating the area under the curve (AUC), sensitivity, specificity, Youden index, positive predictive value (PPV), negative predictive value (NPV), and predicted-to-observed ratio, and performed calibration using Hosmer-Lemeshow test for 11 prediction models.

RESULTS: We enrolled 108 patients, including 44 (40.7%) men, with a mean age of 35.5 years. The mean body mass index was 40.3 ± 9.1 kg/m 2 , the percentage of excess weight loss (%EWL) was (75.9 ± 30.4)%, and the percentage of total weight loss (%TWL) was (29.1± 10.6)%. The mean glycated hemoglobin A1c (HbA1c) level was (7.3 ± 1.8)% preoperatively and decreased to (5.9 ± 1.0)% 5 years after LSG. The 5-year postoperative complete and partial remission rates of T2DM were 50.9% [55/108] and 27.8% [30/108], respectively. Six models, i.e., "ABCD", individualized metabolic surgery (IMS), advanced-DiaRem, DiaBetter, Dixon et al' s regression model, and Panunzi et al 's regression model, showed a good discrimination ability (all AUC >0.8). The "ABCD" (sensitivity, 74%; specificity, 80%; AUC, 0.82 [95% confidence interval [CI]: 0.74-0.89]), IMS (sensitivity, 78%; specificity, 84%; AUC, 0.82 [95% CI: 0.73-0.89]), and Panunzi et al' s regression models (sensitivity, 78%; specificity, 91%; AUC, 0.86 [95% CI: 0.78-0.92]) showed good discernibility. In the Hosmer-Lemeshow goodness-of-fit test, except for DiaRem (P <0.01), DiaBetter (P <0.01), Hayes et al (P = 0.03), Park et al (P = 0.02), and Ramos-Levi et al' s (P <0.01) models, all models had a satifactory fit results (P >0.05). The P values of calibration results of the "ABCD" and IMS were 0.07 and 0.14, respectively. The predicted-to-observed ratios of the "ABCD" and IMS were 0.87 and 0.89, respectively.

CONCLUSION: The prediction model IMS was recommended for clinical use because of excellent predictive performance, good statistical test results, and simple and practical design features.}, } @article {pmid37326525, year = {2023}, author = {Anders, C and Kivlighan, DM}, title = {Identity salience: An intersectional approach to understanding multicultural processes and outcomes in psychotherapy.}, journal = {Journal of counseling psychology}, volume = {70}, number = {5}, pages = {477-485}, doi = {10.1037/cou0000688}, pmid = {37326525}, issn = {0022-0167}, support = {//University of Iowa/ ; }, mesh = {Humans ; *Professional-Patient Relations ; *Psychotherapy/methods ; Surveys and Questionnaires ; Cultural Diversity ; }, abstract = {A growing body of research has demonstrated the importance of therapists' multicultural orientation (MCO), namely, their cultural humility (CH), cultural comfort, and cultural missed opportunities, on treatment processes and outcomes (Davis et al., 2018). However, to date, few research has attempted to identify client factors that may moderate the relationship between therapists' MCO and therapeutic processes and outcomes. Informed by Yakushko et al.'s (2009) identity salience model, this study seeks to advance the MCO literature by examining the saliency of clients' cultural identities, therapists' MCO, and improvement in therapy. Data for this study consisted of 193 individuals who had received at least five sessions of psychotherapy in the last 6 months and responded to an online survey about their experience in therapy. Moderated polynomial regression and response surface analysis was used to examine if the relationship between therapists' MCO and clients' perceived improvement in psychotherapy differed as a function of the salience of clients' first and second most important cultural identities. The results indicated that when clients report only one highly salient cultural identity and perceive their therapist high in cultural humility, they report high levels of improvement. In contrast, when clients reported two highly salient identities, cultural humility and improvement in therapy were not significantly related. (PsycInfo Database Record (c) 2023 APA, all rights reserved).}, } @article {pmid37322525, year = {2023}, author = {Karlsson, AW and Kragh-Sørensen, A and Børgesen, K and Behrens, KE and Andersen, T and Kidholm, ML and Rothmann, MJ and Ketelaar, M and Janssens, A}, title = {Roles, outcomes, and enablers within research partnerships: A rapid review of the literature on patient and public involvement and engagement in health research.}, journal = {Research involvement and engagement}, volume = {9}, number = {1}, pages = {43}, pmid = {37322525}, issn = {2056-7529}, abstract = {BACKGROUND: Recent studies mention a need to investigate partnership roles and dynamics within patient and public involvement and engagement (PPIE) in health research, and how impact and outcomes are achieved. Many labels exist to describe involvement processes, but it is unknown whether the label has implications on partnerships and outcomes. This rapid review investigates how roles between patients, relatives and researchers in a broad variety of PPIE activities in health research are described in peer reviewed papers and explores what enables these partnerships.

METHODS: Rapid review of articles published between 2012 and February 2022 describing, evaluating, or reflecting on experiences of PPIE in health research. All research disciplines and research areas were eligible. Four databases (Medline, Embase, PsychInfo and CINAHL) were searched between November 2021 and February 2022. We followed PRISMA guidelines and extracted descriptive factors: year, origin, research area and discipline, study focus, framework used and co-authorship. On a selection of articles, we performed a narrative analysis of partnership roles using Smits et al.'s. Involvement Matrix. Lastly, we performed a meta synthesis of reported enablers and outcomes of the partnerships. Patients and Relatives (PRs) have been involved in the whole rapid review process and are co-authors of this article.

RESULTS: Seventy articles from various research disciplines and areas were included. Forty articles were selected for a narrative analysis of the role description of PRs and researchers, and a meta synthesis of enablers and outcomes. Most articles described researchers as decision-makers throughout the research cycle. PRs most often were partners when they were included as co-authors; they were mostly partners in the design, analysis, write-up, and dissemination stages. Enablers of partnerships included: PR training, personality of PRs and communication skills, trust, remuneration and time.

CONCLUSIONS: Researchers' decision-making roles gives them control of where and when to include PRs in their projects. Co-authorship is a way of acknowledging patients' contributions which may lead to legitimation of their knowledge and the partnership. Authors describe common enablers, which can help future partnership formation.}, } @article {pmid37318233, year = {2024}, author = {Sutton, SS and Magagnoli, J and Cummings, TH and Hardin, JW and Ambati, J}, title = {Author Reply to Letter to the Editor: In Response to: Comment on Sutton et al.'s "Allopurinol and the Risk of Diabetic Macular Edema among U.S. Veterans with Type 2 Diabetes".}, journal = {Ocular immunology and inflammation}, volume = {32}, number = {7}, pages = {1454-1456}, pmid = {37318233}, issn = {1744-5078}, support = {R01 EY028027/EY/NEI NIH HHS/United States ; R01 DA054992/DA/NIDA NIH HHS/United States ; R01 EY029799/EY/NEI NIH HHS/United States ; VA 999999/VA/VA/United States ; R01 EY031039/EY/NEI NIH HHS/United States ; }, mesh = {Humans ; *Macular Edema/drug therapy/etiology ; *Diabetes Mellitus, Type 2/drug therapy/complications/epidemiology ; *Diabetic Retinopathy/epidemiology/drug therapy ; *Veterans ; United States/epidemiology ; *Allopurinol/therapeutic use ; Risk Factors ; }, } @article {pmid37318224, year = {2024}, author = {Ali, N and Thotathil, A and Niederer, R}, title = {Letter to the Editor: Comment on Fonollosa et al.'s "Hyper-Reflective Outer Nuclear Layer (HONL) in Vogt-Koyanagi-Harada Disease and Sympathetic Ophthalmia".}, journal = {Ocular immunology and inflammation}, volume = {32}, number = {4}, pages = {437-439}, doi = {10.1080/09273948.2023.2217919}, pmid = {37318224}, issn = {1744-5078}, mesh = {Humans ; *Uveomeningoencephalitic Syndrome/diagnosis/complications/drug therapy ; *Ophthalmia, Sympathetic/diagnosis/drug therapy ; *Tomography, Optical Coherence ; }, } @article {pmid37316881, year = {2023}, author = {Khan, T and Coultas, C and Kieslich, K and Littlejohns, P}, title = {The complexities of integrating evidence-based preventative health into England's NHS: lessons learnt from the case of PrEP.}, journal = {Health research policy and systems}, volume = {21}, number = {1}, pages = {53}, pmid = {37316881}, issn = {1478-4505}, mesh = {Humans ; *State Medicine ; Learning ; England ; Health Policy ; *HIV Infections/prevention & control ; }, abstract = {BACKGROUND: The integration of preventative health services into England's National Health Service is one of the cornerstones of current health policy. This integration is primarily envisaged through the removal of legislation that blocks collaborations between NHS organisations, local government, and community groups.

AIMS AND OBJECTIVES: This paper aims to illustrate why these actions are insufficient through the case study of the PrEP judicial review.

METHODS: Through an interview study with 15 HIV experts (commissioners, activists, clinicians, and national health body representatives), we explore the means by which the HIV prevention agenda was actively blocked, when NHS England denied responsibility for funding the clinically effective HIV pre-exposure prophylaxis (PrEP) drug in 2016, a case that led to judicial review. We draw on Wu et al.'s (Policy Soc 34:165-171, 2016) conceptual framing of 'policy capacity' in undertaking this analysis.

RESULTS: The analyses highlight three main barriers to collaborating around evidence-based preventative health which indicate three main competence/capability issues in regard to policy capacity: latent stigma of 'lifestyle conditions' (individual-analytical capacity); the invisibility of prevention in the fragmented health and social care landscape related to issues of evidence generation and sharing, and public mobilisation (organizational-operational capacity); and institutional politics and distrust (systemic-political capacity).

DISCUSSION AND CONCLUSION: We suggest that the findings hold implications for other 'lifestyle' conditions that are tackled through interventions funded by multiple healthcare bodies. We extend the discussion beyond the 'policy capacity and capabilities' approach to connect with a wider range of insights from the policy sciences, aimed at considering the range of actions needed for limiting the potential of commissioners to 'pass the buck' in regard to evidence-based preventative health.}, } @article {pmid37316399, year = {2024}, author = {Tilki, D and Chen, MH and D'Amico, AV}, title = {Reply to Ugo Giovanni Falagario, Alberto Martini, Francesco Pellegrino, et al.'s Letter to the Editor re: Derya Tilki, Ming-Hui Chen, Jing Wu, et al. Prostate-specific Antigen Level at the Time of Salvage Therapy After Radical Prostatectomy for Prostate Cancer and the Risk of Death. J Clin Oncol 2023;41:2428-35.}, journal = {European urology oncology}, volume = {7}, number = {1}, pages = {166}, doi = {10.1016/j.euo.2023.05.009}, pmid = {37316399}, issn = {2588-9311}, mesh = {Male ; Humans ; *Prostate-Specific Antigen ; Salvage Therapy ; Prostate ; *Prostatic Neoplasms/surgery ; Prostatectomy ; }, } @article {pmid37316397, year = {2023}, author = {Yip, W and Ghoreifi, A and Djaladat, H}, title = {Reply to Daniel D. Shapiro, Jose A. Karam, Viraj A. Master, et al.'s Letter to the Editor re: Wesley Yip, Alireza Ghoreifi, Thomas Gerald, et al. Perioperative Complications and Oncologic Outcomes of Nephrectomy Following Immune Checkpoint Inhibitor Therapy: A Multicenter Collaborative Study. Eur Urol Oncol. Eur Urol. Onc. 2023;604-610.}, journal = {European urology oncology}, volume = {6}, number = {6}, pages = {637}, doi = {10.1016/j.euo.2023.05.010}, pmid = {37316397}, issn = {2588-9311}, mesh = {Humans ; *Immune Checkpoint Inhibitors ; Nephrectomy/adverse effects ; *Kidney Neoplasms/surgery ; }, } @article {pmid37312885, year = {2023}, author = {Enns, C and van Vliet, N and Mbane, J and Muhindo, J and Nyumu, J and Bersaglio, B and Massé, F and Cerutti, PO and Nasi, R}, title = {Vulnerability and coping strategies within wild meat trade networks during the COVID-19 pandemic.}, journal = {World development}, volume = {170}, number = {}, pages = {106310}, pmid = {37312885}, issn = {0305-750X}, abstract = {Measures adopted to prevent the spread of COVID-19 and economic shocks caused by the pandemic have affected food networks globally, including wild meat trade networks that support the livelihoods and food security of millions of people around the world. In this article, we examine how COVID-related shocks have affected the vulnerability and coping strategies of different actors along wild meat trade networks. Informed by 1,876 questionnaires carried out with wild meat hunters, traders, vendors, and consumers in Cameroon, Colombia, Democratic Republic of Congo (DRC), and Guyana, the article presents qualitative evidence as to how COVID-19 impacted different segments of society involved in wild meat trade networks. Our findings largely align with McNamara et al. (2020) and Kamogne Tagne et al.'s (2022) causal model hypothesising how the impacts of the pandemic could lead to a change in local incentives for wild meat hunting in sub-Saharan African countries. Like McNamara et al. (2020) and Kamogne Tagne et al. (2022), we find that the pandemic reduced wild meat availability for wild meat actors in urban areas while increasing reliance on wild meat for subsistence purposes in rural areas. However, we find some impact pathways to be more relevant than others, and also incorporate additional impact pathways into the existing causal model. Based on our findings, we argue that wild meat serves as an important safety net in response to shocks for some actors in wild meat trade networks. We conclude by advocating for policies and development interventions that seek to improve the safety and sustainability of wild meat trade networks and protect access to wild meat as an environmental coping strategy during times of crisis.}, } @article {pmid37283936, year = {2023}, author = {Margeta, M}, title = {Neuromuscular disease: 2023 update.}, journal = {Free neuropathology}, volume = {4}, number = {}, pages = {2}, pmid = {37283936}, issn = {2699-4445}, abstract = {This review highlights ten important advances in the neuromuscular disease field that were reported in 2022. As with prior updates in this article series, the overarching topics include (i) advances in understanding of fundamental neuromuscular biology; (ii) new / emerging diseases; (iii) advances in understanding of disease etiology and pathogenesis; (iv) diagnostic advances; and (v) therapeutic advances. Within this general framework, the individual disease entities that are discussed in more detail include neuromuscular complications of COVID-19 (another look at the topic first covered in the 2021 and 2022 reviews), DNAJB4-associated myopathy, NMNAT2-deficient hereditary axonal neuropathy, Guillain-Barré syndrome, sporadic inclusion body myositis, and amyotrophic lateral sclerosis. In addition, the review highlights a few other advances (including new insights into mechanisms of fiber maturation during muscle regeneration and fiber rebuilding following reinnervation, improved genetic testing methods for facioscapulohumeral and myotonic muscular dystrophies, and the use of SARM1 inhibitors to block Wallerian degeneration) that will be of significant interest for clinicians and researchers who specialize in neuromuscular disease.}, } @article {pmid37280625, year = {2023}, author = {Ding, H and Song, Y and Xin, W and Sun, J and Zhong, L and Zhou, Q and He, C and Gong, L and Fang, L}, title = {Reply to "A better interpretation of data regarding the opioid switching to methadone".}, journal = {BMC palliative care}, volume = {22}, number = {1}, pages = {66}, pmid = {37280625}, issn = {1472-684X}, mesh = {Humans ; Methadone/therapeutic use ; Analgesics, Opioid/therapeutic use ; *Cancer Pain ; Dose-Response Relationship, Drug ; *Pain, Intractable/chemically induced ; Palliative Care ; *Neoplasms ; }, abstract = {In our article ?Methadone switching for refractory cancer pain' (BMC palliative care, 2022) we explore the efficacy, safety and economics of methadone in treatment of patients with refractory cancer pain in China. Professor Mercadante provided a better interpretation of data regarding the opioid switching to methadone in the Matters Arising. In this article, we answered the questions in Mercadante et al.'s comments one by one.}, } @article {pmid37262138, year = {2023}, author = {Steed, R and Acquisti, A and Wu, ZS and Liu, T}, title = {Response to comment on "Policy impacts of statistical uncertainty and privacy".}, journal = {Science (New York, N.Y.)}, volume = {380}, number = {6648}, pages = {eadh2297}, doi = {10.1126/science.adh2297}, pmid = {37262138}, issn = {1095-9203}, abstract = {We offer our thanks to the authors for their thoughtful comments. Cui, Gong, Hannig, and Hoffman propose a valuable improvement to our method of estimating lost entitlements due to data error. Because we don't have access to the unknown, "true" number of children in poverty, our paper simulates data error by drawing counterfactual estimates from a normal distribution around the official, published poverty estimates, which we use to calculate lost entitlements relative to the official allocation of funds. But, if we make the more realistic assumption that the published estimates are themselves normally distributed around the "true" number of children in poverty, Cui et al.'s proposed framework allows us to reliably estimate lost entitlements relative to the unknown, ideal allocation of funds-what districts would have received if we knew the "true" number of children in poverty.}, } @article {pmid37255606, year = {2023}, author = {Inglis, D}, title = {Towards a historical sociology of associations and dissociations between food, food events and alcoholic drinks: A reply to Warde et al.}, journal = {Nordisk alkohol- & narkotikatidskrift : NAT}, volume = {40}, number = {3}, pages = {319-322}, pmid = {37255606}, issn = {1458-6126}, abstract = {This commentary reflects on the strengths of the paper by Warde et al. entitled "Situated drinking: the association between eating and alcohol consumption in Great Britain". It suggests that practice-theoretical approaches towards studying contemporary connections between foods, food events and alcoholic drinks provides an excellent basis for overcoming the analytical limits of fields such as food studies, drinks studies, alcohol studies and related areas. This is especially so if Warde et al.'s quantitative methodology were to be yoked to two further sources of inspiration, namely Mary Douglas's structuralist analysis of food combinations within food events and Stephen Mennell's utilisation of the concepts and concerns of Norbert Elias to produce a systematic historical sociology of food. An extended inter-paradigmatic approach to the study of how alcoholic drinks relate to foods and eating practices emerges as a result.}, } @article {pmid37247824, year = {2023}, author = {Harpaz, N and Goldblum, JR and Shepherd, NA and Riddell, RH and Rubio, CA and Vieth, M and Wang, HH and Odze, RD}, title = {Colorectal dysplasia in chronic inflammatory bowel disease: a contemporary consensus classification and interobserver study.}, journal = {Human pathology}, volume = {138}, number = {}, pages = {49-61}, doi = {10.1016/j.humpath.2023.05.008}, pmid = {37247824}, issn = {1532-8392}, mesh = {Humans ; Consensus ; Reproducibility of Results ; Intestines ; *Colorectal Neoplasms ; *Inflammatory Bowel Diseases/complications ; *Carcinoma in Situ ; Hyperplasia ; Chronic Disease ; }, abstract = {The clinical management of patients with dysplasia in chronic inflammatory bowel disease (IBD) is currently guided by Riddell et al.'s grading system (negative, indefinite, low grade, high grade) from 1983 which was based primarily on nuclear cytoarchitectural characteristics. Although most dysplasia in IBD resembles sporadic adenomas morphologically, other distinctive potential cancer precursors in IBD have been described over time. Recognizing the need for a updated comprehensive classification for IBD-associated dysplasia, an international working group of pathologists with extensive clinical and research experience in IBD devised a new classification system and assessed its reproducibility by having each participant assess test cases selected randomly from a repository of electronic images of potential cancer precursor lesions. The new classification system now encompasses three broad categories and nine sub-categories: 1) intestinal dysplasia (tubular/villous adenoma-like, goblet cell deficient, crypt cell, traditional serrated adenoma-like, sessile serrated lesion-like and serrated NOS), 2) gastric dysplasia (tubular/villous and serrated), and 3) mixed intestinal-gastric dysplasia. In the interobserver analysis, 67% of the diagnoses were considered definitive and achieved substantial inter-rater agreement. The key distinctions between intestinal and gastric lesions and between serrated and non-serrated lesions achieved substantial and moderate inter-rater agreement overall, respectively, however, the distinctions among certain serrated sub-categories achieved only fair agreement. Based on the Riddell grading system, definite dysplasia accounted for 86% of the collective responses (75% low grade, 11% high grade). Based on these results, this new classification of dysplasia in IBD can provide a sound foundation for future clinical and basic IBD research.}, } @article {pmid39678215, year = {2023}, author = {Sandejas, BNAI}, title = {Addressing Problems in Accident Management in a Shopping Complex through Action Research.}, journal = {Acta medica Philippina}, volume = {57}, number = {5}, pages = {51-62}, pmid = {39678215}, issn = {2094-9278}, abstract = {INTRODUCTION: Accidents are unpredictable and sometimes unavoidable. Businesses such as shopping complexes need to follow safety protocols to ensure that nobody is hurt. The shopping complex should have preventive measures and an accident management team to offer efficient and timely treatment for these accident victims.

OBJECTIVE: This paper aims to identify problems experienced by the accident management team in dealing with accidents in a shopping complex. The report will also propose and implement solutions to all issues identified.

METHODS: Two action research cycles were conducted for this paper, with the results of the first action research flowing into the second action research cycle. Reeves et al.'s interprofessional teamwork framework addressed concerns related to teamwork. The data used in this action research came from journal entries, informal and formal one-on-one discussions, and discussions with each department.

RESULTS: The workflow for the current post-accident management activities was evaluated. The problems identified were grouped into 5: roles and responsibilities, procedures, knowledge transfer, logistics, and skills. The issues concerning the roles and responsibilities of each team member were addressed by realigning these with their current skills, training, and job description. The remaining and new problems were addressed by developing an accident management policy. Inclusions in the policy are protocols on transporting patients, communication and transportation procedures, letter of authorization (LOA) approval procedures, post-accident evaluation procedures, pre-accident recommendations, policy revision procedures to address organizational changes, changes in the job description or government regulatory mandates, and the evaluation of current skills in case training is needed.

CONCLUSION: Accident management requires a coordinated effort amongst all the team members, with members from different social and health specialties. Using Reeves et al.'s interprofessional teamwork framework, the team identified the problems and implemented solutions by realigning the roles and responsibilities of each team member and implementing an accident management policy that can improve preventive measures and improve post-accident responses.}, } @article {pmid37246928, year = {2023}, author = {Coss-Adame, E and Arenas-Martinez, J}, title = {Thoughts on Ma et al.'s publication: "Clinical efficacy and mechanism of transcutaneous neuromodulation on ineffective esophageal motility in patients with gastroesophageal reflux disease".}, journal = {Neurogastroenterology and motility}, volume = {35}, number = {9}, pages = {e14622}, doi = {10.1111/nmo.14622}, pmid = {37246928}, issn = {1365-2982}, mesh = {Humans ; *Gastroesophageal Reflux/therapy ; Treatment Outcome ; }, } @article {pmid37237247, year = {2023}, author = {Paton, A and Cupit, C and Armstrong, N}, title = {Organising work in neonatal transfer: Optimising place of care for babies born moderately preterm.}, journal = {Sociology of health & illness}, volume = {45}, number = {8}, pages = {1634-1651}, doi = {10.1111/1467-9566.13656}, pmid = {37237247}, issn = {1467-9566}, support = {15/70/104//Health Services and Delivery Research Programme/ ; //Health Foundation Improvement Science Fellowship/ ; //National Institute for Health & Care Research, NIHR Applied Research Collaboration East Midlands, ARC EM/ ; }, mesh = {Infant, Newborn ; Infant ; Pregnancy ; Female ; Humans ; *Parturition ; Gestational Age ; *Parents ; England ; }, abstract = {The organisation of neonatal units into geographically-based networks that offer different levels of care is intended to ensure babies receive the care they need via transfers between different units. In this article, we explore the significant organisational work required in practice to accomplish such transfers. Conducted within a wider study of optimal place of care for babies born between 27 and 31 weeks' gestation, we draw on ethnographic work exploring the accomplishment of transfers in this complex care context. We undertook fieldwork in six neonatal units across two networks in England, representing 280 hours of observation and formal interviews with 15 health-care professionals. Drawing on Strauss et al.'s concept of the social organisation of medicine and Allen's concept of 'organising work', we identify three distinct forms of such work central to the successful accomplishment of a neonatal transfer: (1) 'matchmaking', to identify a suitable transfer location; (2) 'transfer articulation', to successfully effect the planned transfer; and (3) 'parent engagement', to support parents through the transfer process. Our findings build on and extend Strauss et al. and Allen's work by both highlighting the different forms of 'organising work' undertaken in this clinical context and the distribution of such work across different professional groups.}, } @article {pmid37229764, year = {2024}, author = {Turgoose, D and McKie, RE and Connelly, P}, title = {Insurance Discrimination, Companion Animal Harm, and Domestic Violence and Abuse - Double Jeopardy in the UK.}, journal = {Violence against women}, volume = {30}, number = {12-13}, pages = {3350-3371}, pmid = {37229764}, issn = {1552-8448}, mesh = {Humans ; United Kingdom ; *Domestic Violence/statistics & numerical data ; Animals ; *Pets ; Female ; Insurance/statistics & numerical data ; }, abstract = {Prompted by Signal et al.'s study, this research examines UK "Pet Insurance" policies to see if and how experiencing domestic violence and abuse (DVA) in interspecies households is excluded under insurance policies terms. Situating our findings within the existing literature on human and companion animal victims of DVA, we discuss the implications for improving cross-reporting and multi-agency action to protect and prevent harm to humans and companion animal victims of DVA. In turn we identify a series of recommendations to combat discrimination in insurance, set out in our conclusion.}, } @article {pmid37228480, year = {2022}, author = {Barkus, E}, title = {Invited discussant comments during the UCL-Penn Global COVID Study webinar 'How Do We Trust (Again): Paranoia and Mental Health': part 1 of 2.}, journal = {UCL open. Environment}, volume = {4}, number = {}, pages = {e002}, pmid = {37228480}, issn = {2632-0886}, abstract = {The article provides commentary on Wong et al.'s investigation of the relationship between schizotypal traits, social mistrust and aggression, mental and physical health outcomes across three waves of data collection commencing in April 2020. The researchers aimed to consider the nature of the relationship between these variables and the stability of these relationships as coronavirus (Covid-19) restrictions fluctuated over time. Their results suggested that loneliness reflects a hub which links the trait variables of schizotypal and social mistrust to aggression and mental and physical health symptoms. Their network did not vary by demographic factors nor wave of data collection, suggesting that stable individual differences were driving results. Their results propose that interventions which increase social connection could provide positive health benefits as well as decreasing aggression (via reductions in social mistrust). Their data contributes to understanding about how schizotypal traits link to outcomes under conditions of social stress.}, } @article {pmid37227862, year = {2023}, author = {McCabe, GA and Smith, MM and Widiger, TA}, title = {Psychopathy and antisocial personality disorder in the fifth edition of the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders: An attempted replication of Wygant et al. (2016).}, journal = {Personality disorders}, volume = {14}, number = {6}, pages = {636-648}, doi = {10.1037/per0000626}, pmid = {37227862}, issn = {1949-2723}, mesh = {Humans ; Male ; *Antisocial Personality Disorder/diagnosis/psychology ; Diagnostic and Statistical Manual of Mental Disorders ; *Personality Disorders/diagnosis ; Personality ; Personality Inventory ; }, abstract = {The fifth edition of the American Psychiatric Association's (APA) Diagnostic and Statistical Manual of Mental Disorders (DSM-5) Section III Alternative Model of Personality Disorder (AMPD) was developed to ameliorate some of the concerns of the DSM-5 Section II categorical model by moving away from the discrete boundaries of behaviorally specific criteria to a hybridized dimensional trait-based approach. Wygant et al. (2016) examined the extent to which the AMPD improved the operationalization of antisocial personality disorder to more closely align with psychopathy, a notable weakness of DSM-5 Section II (Crego & Widiger, 2015; Lynam & Vachon, 2012; Strickland et al., 2013). Wygant et al. found that the DSM-5 Section III AMPD outperformed Section II in predicting various operationalizations of psychopathy in a sample of 200 male inmates. In the spirit of the importance in exploring replication (Tackett et al., 2017), the current study sought to replicate and extend these findings by comparing the ability of the AMPD and alternative trait models to account for psychopathy. Analyses showed a partial replication of Wygant et al.'s findings, indicating that additional traits to account for psychopathy should be included in DSM-5 Section III. The current study was not preregistered. (PsycInfo Database Record (c) 2023 APA, all rights reserved).}, } @article {pmid37211659, year = {2023}, author = {O'Keefe, DJ}, title = {Commentary on "Do Vaping Prevention Messages Impact Adolescents and Young Adults? A Meta-Analysis of Experimental Studies".}, journal = {Health communication}, volume = {38}, number = {8}, pages = {1723-1726}, doi = {10.1080/10410236.2023.2212467}, pmid = {37211659}, issn = {1532-7027}, mesh = {Humans ; Adolescent ; Young Adult ; *Vaping/prevention & control ; }, abstract = {Preventing vaping by adolescents and young adults is unquestionably an important goal. Ma et al.'s meta-analysis invites the conclusion that vaping prevention messages are effective. This commentary discusses two concerns about that conclusion and the affiliated meta-analysis: (1) None of the analyzed effect sizes describes the effectiveness of vaping prevention messages; the effect sizes describe the difference in effectiveness (the difference on an outcome variable) between the two conditions being compared. (2) As the two conditions being compared vary, so do the relevant conclusions--but the review combines different kinds of comparisons.}, } @article {pmid37206891, year = {2022}, author = {Cave-Freeman, D and Mancini, VO and Wakschlag, LS and Finlay-Jones, A}, title = {Maternal Emotion Regulation and Early Childhood Irritability: The Role of Child Directed Emotion Regulation Strategies.}, journal = {Personality and individual differences}, volume = {196}, number = {}, pages = {}, pmid = {37206891}, issn = {0191-8869}, support = {R01 MH107652/MH/NIMH NIH HHS/United States ; }, abstract = {Parental assistance with children's emotion regulation (ER) is a form of emotion socialization behavior that has recently been operationalized with the development of the Parent Assistance with Child Emotion Regulation (PACER) questionnaire. In line with Eisenberg et al.'s heuristic model of the socialization of emotion, this study sought to test the links between mothers' ER difficulties, their use of ER strategies with their child, and child irritability - a salient dimension of child regulatory difficulties. Cross-sectional data was collected online with mothers (N = 371) of children aged one month to 5 years (M = 2.07 years, SD = 1.25) and data were analysed using hierarchical multiple regression analysis. After controlling for child age and gender, maternal distress, and household income, we found small but significant associations between maternal ER difficulties and child irritability. However, maternal use of ER strategies did not account for further variance in child irritability. These findings suggest that there are meaningful associations between maternal ER and child irritability, although maternal strategies to support child ER appear independent of their own ER capacity. Whilst not associated with child irritability, maternal support for children's ER may be associated with other indicators of mental health risk and resilience.}, } @article {pmid37196907, year = {2023}, author = {Srisuka, W and Takaoka, H and Aupalee, K and Saeung, A}, title = {Simulium (Gomphostilbia) wijiti, a new species of black fly (Diptera: Simuliidae) from northern Thailand and its genetic position with related species in the Simulium ceylonicum species-group.}, journal = {Acta tropica}, volume = {244}, number = {}, pages = {106947}, doi = {10.1016/j.actatropica.2023.106947}, pmid = {37196907}, issn = {1873-6254}, mesh = {Animals ; Female ; Male ; *Simuliidae ; Thailand ; Phylogeny ; Larva ; Pupa ; }, abstract = {A new black fly species, Simulium (Gomphostilbia) wijiti, is described based on adult females, males, pupal exuviae and mature larvae from Mae Hong Son Province, Thailand. This new species is placed in the Simulium ceylonicum species-group. It is distinguished from four Thai members of the S. ceylonicum species-group [S. (G.) curtatum Jitklang et al., S. (G.) pangsidaense Takaoka, Srisuka & Saeung, S. (G.) sheilae Takaoka & Davies, and S. (G.) trangense Jitklang et al.], in the female by the short to medium long sensory vesicle; in the male by the large number of upper-eye (large) facets in 15 vertical columns and 15 or 16 horizontal rows; in the pupa by the dorsum of abdominal segments darkened; and in the larva by the antenna as long as or slightly shorter than the stem of the labral fan (longer than the stem of the labral fan in four other species). Phylogenetic analysis based on the COI gene sequences revealed that this new species is genetically closely related to S. leparense of the S. ceylonicum species-group, but is clearly separated from the latter species, and also from the three Thai related species (S. curtatum, S. sheilae and S. trangense) of the same species-group with interspecific genetic distances ranging from 9.65% to 12.67%. This is the fifth member of the S. ceylonicum species-group recorded from Thailand.}, } @article {pmid37193974, year = {2023}, author = {Lawes-Wickwar, S and Lovat, E and Alao, A and Hamer-Hunt, J and Yurtoglu, N and Jensen, C and Clarke, N and Roberts, N and Park, S}, title = {Digital undergraduate medical education and patient and carer involvement: a rapid systematic review of current practice.}, journal = {BMC medical education}, volume = {23}, number = {1}, pages = {335}, pmid = {37193974}, issn = {1472-6920}, mesh = {Humans ; Caregivers ; *Education, Medical, Undergraduate ; Health Personnel/education ; Learning ; *Students, Medical ; }, abstract = {BACKGROUND: Involving patients and carers in medical students' learning aims to centralise the perspective of healthcare users and supports our future medical workforce in the development of key skills. Medical schools are increasingly using digital technology for teaching and it is timely to understand how to maintain patient and carer involvement in this context.

METHODS: Ovid MEDLINE, Ovid EMBASE and medRxiv were searched in October 2020 and reference lists of key articles were hand searched. Eligible studies reported authentic patient or carer involvement in undergraduate medical education where technology was also used. Study quality was assessed by the Mixed Methods Appraisal Tool (MMAT). Levels of patient or carer involvement were assessed using Towle et al.'s (2010) taxonomy, from Level 1 (lowest level) to Level 6 (highest level).

RESULTS: Twenty studies were included in this systematic review. In 70% of studies, patients and carers featured in video or web-based case scenarios with no interaction between healthcare users and students. The remaining 30% of studies reported real-time interactions between students and patients via remote clinical encounters. Digital teaching sessions involving patients or carers were perceived to be valuable by students and educators, and increased student engagement, patient-centred attitudes, clinical knowledge, and communication skills. No studies reported the perspective of patients or carers.

DISCUSSION: Digital technology has not yet driven higher levels of patient and carer involvement in medical training. "Live" interactions between students and patients are becoming more common but challenges need addressing to ensure positive experiences for all involved. Future teaching should enhance the role of patients and carers in medical education and support them to overcome any potential barriers to doing so remotely.}, } @article {pmid37192499, year = {2023}, author = {Miller, MQ and Hadlock, TA}, title = {Commentary on: "Chemodenervation Algorithm: Functional and Aesthetic Considerations for Facial Harmony in Patients with Post-Facial Paralysis Synkinesis," by Hetzler et al.}, journal = {Facial plastic surgery & aesthetic medicine}, volume = {25}, number = {6}, pages = {519-520}, doi = {10.1089/fpsam.2023.0111}, pmid = {37192499}, issn = {2689-3622}, mesh = {Humans ; *Facial Paralysis ; *Synkinesis/drug therapy/etiology ; *Nerve Block ; Outcome Assessment, Health Care ; Patients ; }, abstract = {In this commentary, we discuss Hetzler et al.'s article, "Chemodenervation Algorithm: Functional and Aesthetic Considerations for Facial Harmony in Patients with Post-Facial Paralysis Synkinesis." The authors do an excellent job of presenting a guide for practitioners to use when initiating chemodenervation treatment for patients with nonflaccid facial paralysis. Standardization of outcome assessment tools and rigorous data collection will further refine treatment algorithms.}, } @article {pmid37183300, year = {2023}, author = {Nelsen, J and Shive, N and Bennett, CR and Coats, H}, title = {Experiences of dignity: Age at onset of serious illness matters.}, journal = {Nursing ethics}, volume = {30}, number = {7-8}, pages = {1038-1050}, pmid = {37183300}, issn = {1477-0989}, support = {R00 NR016686/NR/NINR NIH HHS/United States ; }, mesh = {Humans ; Qualitative Research ; *Respect ; Age of Onset ; *Renal Dialysis ; Feminism ; }, abstract = {BACKGROUND: Preserving persons' dignity is integral to nursing. More research is needed to explore how a diversity of patients, particularly those that experience illness from a young age, experience dignity.

AIM: Describe the characteristics of dignity for persons living with serious illness.

RESEARCH DESIGN: Using a secondary data set of twenty audio-recorded interviews, a thematic content analysis was conducted to identify characteristics of dignity. The research team employed van Gennip et al.'s, 2013 "Model of Dignity in Illness" (1) to create a codebook, which the authors utilized to independently code twenty narrative interview transcripts.

Twenty persons living with serious illness of heart failure and/or dialysis-dependent renal failure who were admitted in an acute care hospital.

ETHICAL CONSIDERATIONS: This study was approved on August 26, 2019, by the Colorado Multiple Institutional Review Board (COMIRB) IRB Protocol #19-1874.

FINDINGS: Early-onset participants expressed markedly different dignity concerns than late-onset participants. In the individual domain, early-onset participants felt that their illness was "normal"; they did not experience the "healthy person to patient" transition described by older onset participants. In the relational domain, early-onset participants expressed that their relationships had already integrated their illness while late-onset participants felt that their illness harmed many of their relationships. In the societal domain, early-onset participants described dignity concerns related to how society impacted their ability to financially support themselves during their illness.

DISCUSSION: Differences in the dignity experience of early-onset and late-onset participants are informed by Erikson's "Model of Development" and by Aranda and Jones feminist critique of dignity in healthcare.

CONCLUSIONS: Persons with early-onset illness experience dignity differently. Awareness of the importance of work and financial independence to the experience of dignity for seriously ill patients may enhance persons' dignity experience.}, } @article {pmid37181040, year = {2023}, author = {Cao, S and Hu, X and Shao, Y and Wang, Y and Tang, Y and Ren, S and Li, X}, title = {Relationship between weight-adjusted-waist index and erectile dysfunction in the United State: results from NHANES 2001-2004.}, journal = {Frontiers in endocrinology}, volume = {14}, number = {}, pages = {1128076}, pmid = {37181040}, issn = {1664-2392}, mesh = {Male ; Adult ; Humans ; *Erectile Dysfunction/diagnosis/epidemiology ; Nutrition Surveys ; Risk Factors ; Obesity ; Adiposity ; }, abstract = {OBJECTIVE: The purpose of this study is to examine the association between a novel adiposity parameter, the weight-adjusted-waist index (WWI), and erectile dysfunction (ED).

METHODS: According to National Health and Nutrition Examination Survey (NHANES) 2001-2004, a total of 3884 participants were categorized as ED and non-ED individuals. WWI was calculated as waist circumference (WC, cm) divided by the square root of weight (kg). Weighted univariable and multivariable logistic regression models were conducted to assess the correlation between WWI and ED. Smooth curve fitting was utilized to examine the linear association. The receiver operating characteristic (ROC) curve and DeLong et al.'s test were applied to compare the area under curve (AUC) value and predictive power among WWI, body mass index (BMI), and WC for ED.

RESULTS: WWI was positively related to ED with the full adjustment [odds ratio (OR)=1.75, 95% confidence interval (95% CI): 1.32-2.32, p=0.002]. After converting WWI to a categorical variable by quartiles (Q1-Q4), compared to Q1 the highest WWI quartile was linked to an obviously increased likelihood of ED (OR=2.78, 95% CI: 1.39-5.59. p=0.010). Subgroup analysis revealed the stability of the independent positive relationship between WWI and ED. It was shown that WWI had a stronger prediction for ED (AUC=0.745) than BMI (AUC=0.528) and WC (AUC=0.609). Sensitivity analysis was performed to verify the significantly positive connection between WWI and stricter ED (OR=2.00, 95% CI: 1.36-2.94, p=0.003).

CONCLUSION: An elevated WWI was related to higher risks of ED in the United State adults, and a stronger predictive power of WWI for ED was observed than BMI and WC.}, } @article {pmid37178447, year = {2024}, author = {Gutiérrez-Tiznado, P and López-Lázaro, S and Fonseca, GM}, title = {Age estimation by evaluation of obliteration of the palatine sutures: a scoping review.}, journal = {Forensic science, medicine, and pathology}, volume = {20}, number = {2}, pages = {716-723}, pmid = {37178447}, issn = {1556-2891}, mesh = {Humans ; *Age Determination by Skeleton/methods ; *Cranial Sutures ; Palate, Hard/pathology ; Forensic Anthropology/methods ; Palate/pathology ; }, abstract = {The age estimation (AE) of human remains is a challenging task since it is dependent on the state in which these remains are found. Since the macroscopic evaluation of palatal sutures has been proposed as a method for AE, the aim of this study was to review the literature on this method, considering that the cases of edentulous elderly are among the greatest challenges in anthropological and forensic contexts. A scoping review was performed using a specific search strategy in PubMed, Web of Science, SciELO, LILACS, and Google Scholar. The search identified 13 articles, among which the USA yielded the most information with 3 articles. Only 1 study was identified in Latin America (Peru). There was great diversity regarding the origin of samples, and the studies were carried out on both historical and modern populations. Only 6 articles exceeded the average sample size (168.08) and 4 articles studied samples of fewer than 100 individuals. Although 6 different methods were identified, Mann et al.'s revised method was the most used. The selection of appropriate methods for AE depends on what skeletal elements are present and the general age of the specimens. Although evaluation of the obliteration of the palatal sutures has been found to be simple and promising for AE in individuals over 60 years of age, this method has been reported to have less precision than other more complex methods, which makes the use of a combination of methods necessary to increase the level of confidence and the percentage of success. Further research could resolve this weakness, and methodological refinement (perhaps the digitization and automation of processes, or the application of Bayesian methodology) could provide the necessary solidity to comply with international standards in the forensic scenario.}, } @article {pmid37171705, year = {2023}, author = {Poonai, N and Creene, C and Dobrowlanski, A and Geda, R and Hartling, L and Ali, S and Bhatt, M and Trottier, ED and Sabhaney, V and O'Hearn, K and Jain, R and Osmond, MH}, title = {Inhaled nitrous oxide for painful procedures in children and youth: a systematic review and meta-analysis.}, journal = {CJEM}, volume = {25}, number = {6}, pages = {508-528}, pmid = {37171705}, issn = {1481-8043}, mesh = {Child ; Adolescent ; Humans ; Nitrous Oxide/adverse effects ; Midazolam ; *Ketamine ; *Lacerations ; Pain ; Anesthetics, Local ; Lidocaine, Prilocaine Drug Combination ; Oxygen ; }, abstract = {OBJECTIVES: The objective of this study was to synthesize indication-based evidence for N2O for distress and pain in children.

STUDY DESIGN: We included trials of N2O in participants 0-21 years, reporting distress or pain for emergency department procedures. The primary outcome was procedural distress. Where meta-analysis was not possible, we used Tricco et al.'s classification of "neutral" (p ≥ 0.05), "favorable," or "unfavorable" (p < 0.05, supporting N2O or comparator, respectively). We used the Cochrane Collaboration's Risk of Bias tool and the Grading of Recommendations Assessment, Development, and Evaluation system to evaluate risk of bias and quality of evidence, respectively.

RESULTS: We included 30 trials. For pain using the Visual Analog Scale (0-100 mm) during IV insertion, 70% N2O (delta:-16.5; 95%CI:-28.6 to -4.4; p = 0.008; three trials; I[2] = 0%) and 50% N2O plus eutectic mixture of local anesthetics (EMLA) (delta:-1.2; 95%CI:-2.1 to -0.3; p = 0.007; two trials; I[2] = 43%) were superior to EMLA. 50% N2O was not superior to EMLA (delta:-0.4; 95%CI:-1.2 to 0.3; p = 0.26; two trials; I[2] = 15%). For distress and pain during laceration repair, N2O was "favorable" versus each of SC lidocaine, oxygen, and oral midazolam but "neutral" versus IV ketamine (five trials). For distress and pain during fracture reduction (three trials), N2O was "neutral" versus each of IM meperidine plus promethazine, regional anesthesia, and IV ketamine plus midazolam. For distress and pain during lumbar puncture (one trial), N2O was "favorable" versus oxygen. For distress and pain during urethral catheterization (one trial), N2O was "neutral" versus oral midazolam. For pain during intramuscular injection (one trial), N2O plus EMLA was "favorable" versus N2O and EMLA alone. Common adverse effects of N2O included nausea (4.4%), agitation (3.7%), and vomiting (3.6%) AEs were less frequent with N2O alone (278/1147 (24.2%)) versus N2O plus midazolam (48/52 (92.3%)) and N2O plus fentanyl (123/201 (61.2%)).

CONCLUSIONS: There is sufficient evidence to recommend N2O plus topical anesthetic for IV insertion and laceration repair. Adverse effects are greater when combined with other sedating agents.}, } @article {pmid37166838, year = {2023}, author = {French, BH and Neville, HA and Lewis, JA and Mosley, DV and Adames, HY and Chavez-Dueñas, NY}, title = {"We can create a better world for ourselves": Radical hope in communities of color.}, journal = {Journal of counseling psychology}, volume = {70}, number = {4}, pages = {327-340}, doi = {10.1037/cou0000670}, pmid = {37166838}, issn = {0022-0167}, mesh = {Adult ; Humans ; *Racism/prevention & control/psychology ; Mental Health ; Racial Groups ; }, abstract = {The negative impact of racism on Black, Indigenous, and People of Color's (BIPOC's) mental and physical health is well-documented. Research supports the critical role of personal hope as a buffer against despair and adverse health outcomes among BIPOC. However, there is a dearth of empirical research exploring the experiences of BIPOC's sense of collective hope. This study aimed to help fill this gap in the literature by extending Mosley et al.'s (2020) multidimensional psychological framework of radical hope via a qualitative study. Radical hope includes a collective motivation of hope for BIPOC communities to work toward a more egalitarian future. In this study, focus groups and interviews were conducted with 29 BIPOC adults, with and without mental health training, to explore participants' perceptions of radical hope. Seven interrelated themes were identified. Two core components and four themes aligned with and extended Mosley et al.'s (2020) framework: Collective Orientation, Faith and Agency, Resisting Racism, Embracing Racial Pride, Envisioning Possibilities, and Meaning Making and Purpose. We also identified a new theme, Valuing Self. Implications for clinical practice and research are discussed. (PsycInfo Database Record (c) 2023 APA, all rights reserved).}, } @article {pmid37163189, year = {2023}, author = {Sandset, T and Villadsen, K}, title = {Pandemic modelling and model citizens: Governing COVID-19 through predictive models, sovereignty and discipline.}, journal = {The Sociological review}, volume = {71}, number = {3}, pages = {624-641}, pmid = {37163189}, issn = {0038-0261}, abstract = {Pandemic modelling functions as a means of producing evidence of potential events and as an instrument of intervention that Tim Rhodes and colleagues describe as entangling science into social practices, calculations into materializations, abstracts into effects and models into society. This article seeks to show how a model society evinced through mathematical models produces a model not only for society but also for citizens, showing them how to act in a certain model manner that prevents an anticipated pandemic future. To this end, we analyse political speeches by various Norwegian ministers to elucidate how various model-based COVID-19 responses enact a 'model citizen'. Theoretically, we combine Rhodes et al.'s arguments with Foucault's concepts of law, discipline and security, thus showing what a model society might imply for the model citizen. Finally, we conclude that although the model society is largely informed by epidemiological models and liberal biopolitics that typically place responsibility on individual subjects, sovereign state power remains manifestly present in the speeches' rhetoric.}, } @article {pmid37162154, year = {2023}, author = {Macias, W and Lee, M}, title = {Refining the online health information searcher typology: Applying the patient health engagement model.}, journal = {Health information and libraries journal}, volume = {}, number = {}, pages = {}, doi = {10.1111/hir.12486}, pmid = {37162154}, issn = {1471-1842}, support = {//Texas Christian University/ ; }, abstract = {BACKGROUND: Despite numerous quantitative findings on online health information seeking, little is known about the process of online health information seeking itself.

OBJECTIVES: The study aimed to learn about how adults search for health information online, whether Macias et al.'s Online Health Searcher Typology applies to a broader, non-university sample, and to better identify and understand online health searchers by employing the Patient Health Engagement (PHE) model.

METHODS: This study examined the role of engagement in online health information search processes using think-aloud qualitative interviews with 11 participants in their 30s to 70s. The research applied both thematic analysis and a quantitative coding scheme based on the PHE model to analyse the qualitative data that consists of 500 pages of think-aloud verbatim transcripts.

RESULTS: This study found that four (flounderer, skimmer, digester and devourer) out of five types emerged as distinct search styles. Insights into engagement helped distinguish online health searcher types in this sample.

CONCLUSION: The dynamics of the engagement dimension indicate that the online health information search process is multi-dimensional. It is comprised of different levels of cognitive, emotional, and conative responses, further extending the PHE model. Health science librarians and health professionals have a unique opportunity to help individuals better navigate online health search.}, } @article {pmid37161178, year = {2023}, author = {Zhang, J and Ogiela, U and Taniar, D and Nedjah, N}, title = {Improved cloud storage auditing scheme with deduplication.}, journal = {Mathematical biosciences and engineering : MBE}, volume = {20}, number = {5}, pages = {7905-7921}, doi = {10.3934/mbe.2023342}, pmid = {37161178}, issn = {1551-0018}, abstract = {Cloud storage has become a crucial service for many users who deal with big data. The auditing scheme for cloud storage is a mechanism that checks the integrity of outsourced data. Cloud storage deduplication is a technique that helps cloud service providers save on storage costs by storing only one copy of a file when multiple users outsource the same file to cloud servers. However, combining storage auditing and deduplication techniques can be challenging. To address this challenge, in 2019 Hou et al. proposed a cloud storage auditing scheme with deduplication that supports different security levels of data popularity. This proposal is interesting and has practical applications. However, in this paper, we show that their proposal has a flaw: the cloud or other adversaries can easily forge the data block's authenticators, which means the cloud can delete all the outsourced encrypted data blocks but still provide correct storage proof for the third-party auditor. Based on Hou et al.'s scheme, we propose an improved cloud storage auditing scheme with deduplication and analyze its security. The results show that the proposed scheme is more secure.}, } @article {pmid37154146, year = {2023}, author = {Breithaupt, F and Hicks, M and Hiskes, B and Lagrange, V}, title = {High-stakes decisions do not require narrative conviction but narrative flexibility.}, journal = {The Behavioral and brain sciences}, volume = {46}, number = {}, pages = {e85}, doi = {10.1017/S0140525X22002606}, pmid = {37154146}, issn = {1469-1825}, mesh = {Humans ; Uncertainty ; *Decision Making ; }, abstract = {We challenge Johnson et al.'s assumption that people reduce unclear situations to a single narrative explanation and that such reduction would be adaptive for decision-making under radical uncertainty. Instead, we argue that people imagine and maintain multiple narrative possibilities throughout the decision-making process and that this process provides cognitive flexibility and adaptive benefits within the proposed model.}, } @article {pmid37154139, year = {2023}, author = {Caldwell, L}, title = {Conviction Narrative Theory gains from a richer formal model.}, journal = {The Behavioral and brain sciences}, volume = {46}, number = {}, pages = {e86}, doi = {10.1017/S0140525X2200262X}, pmid = {37154139}, issn = {1469-1825}, abstract = {Conviction Narrative Theory (CNT) is a convincing descriptive theory, and Johnson et al.'s formal model is a welcome contribution to building more precise, testable hypotheses. However, some extensions to the proposed model would make it better defined and more powerful. The suggested extensions enable the model to go beyond CNT, predicting choice outcomes and explaining affective phenomena.}, } @article {pmid37150801, year = {2024}, author = {Aharoni, M and Breska, A and Müller, MM and Schröger, E}, title = {Mechanisms of sustained perceptual entrainment after stimulus offset.}, journal = {The European journal of neuroscience}, volume = {59}, number = {5}, pages = {1047-1060}, doi = {10.1111/ejn.16032}, pmid = {37150801}, issn = {1460-9568}, support = {//Deutsche Forschungsgemeinschaft/ ; }, mesh = {Humans ; *Brain ; *Event-Related Potentials, P300 ; }, abstract = {Temporal alignment of neural activity to rhythmic stimulation has been suggested to result from a resonating internal neural oscillator mechanism, but can also be explained by interval-based temporal prediction. Here, we investigate behavioural and brain responses in the post-stimulation period to compare an oscillatory versus an interval-based account. Hickok et al.'s (2015) behavioural paradigm yielded results that relate to a neural oscillatory entrainment mechanism. We adapted the paradigm to an event-related potential (ERP) suitable design: a periodic sequence was followed, in half of the trials, by near-threshold targets embedded in noise. The targets were played in various phases in relation to the preceding sequences' period. Participants had to detect whether targets were played or not, and their EEG was recorded. Both behavioural results and the P300 component of the ERP were not only partially consistent with an oscillatory mechanism but also partially consistent with an interval-based attentional gain mechanism. Instead, data obtained in the post-entrainment period can best be explained with a combination of both mechanisms.}, } @article {pmid37145497, year = {2024}, author = {Lai, SW}, title = {Comment on Sutton et al.'s "Allopurinol and the Risk of Diabetic Macular Edema Among U.S. Veterans with Type 2 Diabetes".}, journal = {Ocular immunology and inflammation}, volume = {32}, number = {7}, pages = {1509}, doi = {10.1080/09273948.2023.2209169}, pmid = {37145497}, issn = {1744-5078}, mesh = {Humans ; *Macular Edema/epidemiology/drug therapy/etiology ; *Diabetes Mellitus, Type 2/complications/drug therapy/epidemiology ; *Diabetic Retinopathy/epidemiology ; *Veterans ; United States/epidemiology ; *Allopurinol/therapeutic use/adverse effects ; Risk Factors ; }, } @article {pmid37142911, year = {2024}, author = {Rollins, PR and Rangel-Uribe, C and Rojas, R and Brantley, S}, title = {Examining Cultural and Linguistic Sensitivity of Pathways Early Autism Intervention with Hispanic Families.}, journal = {Journal of autism and developmental disorders}, volume = {54}, number = {7}, pages = {2564-2577}, pmid = {37142911}, issn = {1573-3432}, support = {THECB AGP 2018-2020 #20476; NCE #22842//Texas Higher Education Coordinating Board/ ; THECB AGP 2020-2022 #22974, NCE #22974//Texas Higher Education Coordinating Board/ ; }, mesh = {Humans ; *Hispanic or Latino/psychology ; Male ; Female ; Child, Preschool ; *Parents ; *Autistic Disorder/ethnology/psychology/therapy ; Adult ; Early Intervention, Educational/methods ; Language ; Autism Spectrum Disorder/ethnology/psychology/therapy ; }, abstract = {PURPOSE: This research aimed to evaluate evidence of Pathways parent-mediated early autism intervention as a culturally and linguistically sensitive intervention (CLSI) for Hispanic families with autistic children.

METHODS: We used Bernal et al.'s ecologically valid (EV) framework to evaluate current practice and Hispanic parents' perceptions of Pathways 1 ½ years after completing the intervention. Both quantitative and qualitative methods were used. Nineteen parents were contacted, of which 11 completed a semi-structured interview about their experience with Pathways.

RESULTS: On average, the group that completed the interview was less educated, had more monolingual Spanish speakers, and rated their general experience with the intervention slightly more positively than those who did not agree to complete the interview. A review of Pathways's current practices through the lens of the EV framework suggested that Pathways was a CLSI for Hispanic participants in the domains of context, methods, language, and persons. Parental interviews echoed these strengths. However, Pathways did less well balancing evidence-based intervention strategies for autistic children with the heritage value of respeto.

CONCLUSION: Pathways demonstrated strengths regarding cultural and linguistic sensitivity for Hispanic families with young autistic children. Future work with our community stakeholder group will integrate heritage and majority culture perspectives to strengthen Pathways as a CLSI.}, } @article {pmid37140842, year = {2023}, author = {Janík, M and Hejna, P}, title = {Letter regarding Ledinek et al.'s "Death from exsanguination due to power drill injuries in a complex suicide".}, journal = {Forensic science, medicine, and pathology}, volume = {19}, number = {4}, pages = {630-632}, pmid = {37140842}, issn = {1556-2891}, mesh = {Humans ; *Exsanguination/etiology ; *Suicide ; Autopsy ; }, } @article {pmid37133671, year = {2023}, author = {Bruinvels, G and Hackney, AC and Pedlar, CR}, title = {Authors' Reply to Carina Enea et al.'s Comment on "Menstrual Cycle: The Importance of Both the Phases and the Transitions Between Phases on Training and Performance".}, journal = {Sports medicine (Auckland, N.Z.)}, volume = {53}, number = {3}, pages = {763-764}, pmid = {37133671}, issn = {1179-2035}, support = {R03 AR055262/AR/NIAMS NIH HHS/United States ; }, mesh = {Female ; Humans ; *Menstrual Cycle ; }, } @article {pmid37132030, year = {2023}, author = {Pearce, L and Costa, N and Sherrington, C and Hassett, L}, title = {Implementation of digital health interventions in rehabilitation: A scoping review.}, journal = {Clinical rehabilitation}, volume = {37}, number = {11}, pages = {1533-1551}, doi = {10.1177/02692155231172299}, pmid = {37132030}, issn = {1477-0873}, mesh = {Humans ; *Rehabilitation ; *Telemedicine ; }, abstract = {OBJECTIVE: Digital health interventions have potential to enhance rehabilitation services by increasing accessibility, affordability and scalability. However, implementation of digital interventions in rehabilitation is poorly understood. This scoping review aims to map current strategies, research designs, frameworks, outcomes and determinants used to support and evaluate the implementation of digital interventions in rehabilitation.

DATA SOURCES: Comprehensive searches from inception until October 2022 of MEDLINE, CINAHL, PsycINFO, PEDro, SpeechBITE, NeuroBITE, REHABDATA, WHO International Clinical Trial Registry and the Cochrane Library.

METHODS: Two reviewers screened studies against the eligibility criteria. Implementation science taxonomies and methods, including Powell et al.'s compilation of implementation strategies, were used to guide analysis and synthesis of findings.

RESULTS: The search retrieved 13,833 papers and 23 studies were included. Only 4 studies were randomised controlled trials and 9 studies (39%) were feasibility studies. Thirty-seven discrete implementation strategies were reported across studies. Strategies related to training and educating clinicians (91%), providing interactive assistance (61%), and developing stakeholder interrelationships (43%) were most frequently reported. Few studies adequately described implementation strategies and methods for selecting strategies. Almost all studies measured implementation outcomes and determinants; most commonly, acceptability, compatibility and dose delivered of digital interventions.

CONCLUSION: The rigour of implementation methods in the field is currently poor. Digital interventions require carefully planned and tailored implementation to facilitate successful adoption into rehabilitation practice. To keep pace with rapidly advancing technology, future rehabilitation research should prioritise using implementation science methods to explore and evaluate implementation while testing effectiveness of digital interventions.}, } @article {pmid37131211, year = {2023}, author = {Maas, J and Simeunovic-Ostojic, M and Bodde, NMG}, title = {Is a dissonance-based group intervention targeting thin-ideal internalization a successful potential add-on for specialized eating disorder care? A randomized feasibility and acceptability pilot study.}, journal = {Journal of eating disorders}, volume = {11}, number = {1}, pages = {68}, pmid = {37131211}, issn = {2050-2974}, abstract = {BACKGROUND: Dissonance-based eating disorder programs have successfully targeted body dissatisfaction by challenging the thin beauty ideal in the preventive context and in groups of patients with a subthreshold and full threshold DSM-5 eating disorder. As there is a need for interventions specifically targeting thin-ideal internalization in (highly) specialized treatment centres, the present study adapted Stice's et al.'s Body Project for its use as an add-on treatment for severe eating disorders with the aims to identify whether it was feasible and acceptable in this treatment context, to determine any necessary modifications with regard to the treatment and study procedures, and to test preliminary effectiveness.

METHODS: The study was a randomized controlled pilot/feasibility trial. Thirty patients started in the Body Project group and 25 in the Psycho-education group. Measurements took place pre- and post-intervention, and at three and six months follow-up. Patients and staff evaluated treatment and study procedures, and patients completed questionnaires on thin-ideal internalization, body dissatisfaction, self-objectification, negative affect and eating disorder pathology.

RESULTS: The Body Project group and Psycho-education group both proved highly feasible and acceptable, as well as preliminarily effective, based on quantitative scores and qualitative feedback. Preliminary analyses showed that treatment effects did not differ between treatment groups. As both groups were an add-on to standard treatment, treatment effects cannot be disentangled from effects resulting from standard treatment. Qualitative feedback for the Body Project group included several recommendations for future implementation: increasing the number of treatment sessions, creating homogeneous therapy groups, and optimizing timing of the treatment.

CONCLUSIONS: Future research should examine further modifications to the Body Project group for severe eating disorders, as well as for whom, and when in the course of treatment the intervention is most effective. The present study also showed the benefits of implementing a structured Psycho-education group. We tested the feasibility and acceptability of a group intervention targeting the thin beauty ideal (Body Project group) in patients with severe eating disorders and compared this intervention to a group intervention focusing on psycho-education about eating disorders (Psycho-education group). Both interventions were added to standard treatment. We adapted the protocol for patients with severe eating disorders. Both the Body Project group and the Psycho-education group were evaluated by patients as well as staff as highly feasible and acceptable, and effects were positive. Treatment effects did not differ between treatment groups. As both treatments were an add-on to standard treatment, treatment effects cannot be disentangled from effects resulting from standard treatment. The study suggested further modifications to the Body Project group. Future research should examine these modifications as well as for whom, and when in the course of treatment the intervention is most effective. The present study also showed the benefits of implementing a structured Psycho-education group.}, } @article {pmid37125795, year = {2023}, author = {Moore, EE and Moore, HB and Thomas, SG and Farrell, MS and Sixta, S and Coleman, JR and Miller, JB and Bunch, CM and Waxman, D and Walsh, MM}, title = {Serial "death diamond" TEGs are a bedside indicator of futile resuscitation during massive transfusion.}, journal = {The journal of trauma and acute care surgery}, volume = {95}, number = {3}, pages = {e19-e21}, pmid = {37125795}, issn = {2163-0763}, mesh = {Humans ; *Blood Transfusion ; Resuscitation ; Medical Futility ; *Wounds and Injuries ; }, abstract = {Serial DDs could serve as rapid check points to gauge the likelihood of success of continued resuscitation. Loudon et al.’s work combined with the use of serial DDs may serve as building blocks toward a trial using VETs to predict continued futile resuscitation.}, } @article {pmid37119320, year = {2023}, author = {Neumann, JO and Schmidt, S and Nohman, A and Jakobs, M and Unterberg, A}, title = {Routine ICU admission after brain tumor surgery: retrospective validation and critical appraisal of two prediction scores.}, journal = {Acta neurochirurgica}, volume = {165}, number = {6}, pages = {1655-1664}, pmid = {37119320}, issn = {0942-0940}, mesh = {Adult ; Humans ; Retrospective Studies ; *Hospitalization ; Intensive Care Units ; Postoperative Complications/epidemiology ; *Brain Neoplasms/surgery ; }, abstract = {BACKGROUND: Routine admission to an intensive care unit (ICU) following brain tumor surgery has been a common practice for many years. Although this practice has been challenged by many authors, it has still not changed widely, mainly due to the lack of reliable data for preoperative risk assessment. Motivated by this dilemma, risk prediction scores for postoperative complications following brain tumor surgery have been developed recently. In order to improve the ICU admission policy at our institution, we assessed the applicability, performance, and safety of the two most appropriate risk prediction scores.

METHODS: One thousand consecutive adult patients undergoing elective brain tumor resection within 19 months were included. Patients with craniotomy for other causes, i.e., cerebral aneurysms and microvascular decompression, were excluded. The decision for postoperative ICU-surveillance was made by joint judgment of the operating surgeon and the anesthesiologist. All data and features relevant to the scores were extracted from clinical records and subsequent ICU or neurosurgical floor documentation was inspected for any postoperative adverse events requiring ICU admission. The CranioScore derived by Cinotti et al. (Anesthesiology 129(6):1111-20, 5) and the risk assessment score of Munari et al. (Acta Neurochir (Wien) 164(3):635-641, 15) were calculated and prognostic performance was evaluated by ROC analysis.

RESULTS: In our cohort, both scores showed only a weak prognostic performance: the CranioScore reached a ROC-AUC of 0.65, while Munari et al.'s score achieved a ROC-AUC of 0.67. When applying the recommended decision thresholds for ICU admission, 64% resp. 68% of patients would be classified as in need of ICU surveillance, and the negative predictive value (NPV) would be 91% for both scores. Lowering the thresholds in order to increase patient safety, i.e., 95% NPV, would lead to ICU admission rates of over 85%.

CONCLUSION: Performance of both scores was limited in our cohort. In practice, neither would achieve a significant reduction in ICU admission rates, whereas the number of patients suffering complications at the neurosurgical ward would increase. In future, better risk assessment measures are needed.}, } @article {pmid37106462, year = {2023}, author = {Jalilian, K and Momeni, K and Jebraeili, H}, title = {The mediating role of early maladaptive schemas in the relationship between attachment styles and loneliness.}, journal = {BMC psychology}, volume = {11}, number = {1}, pages = {136}, pmid = {37106462}, issn = {2050-7283}, mesh = {Adult ; Humans ; *Loneliness ; *Emotions ; Affect ; Students/psychology ; Object Attachment ; }, abstract = {BACKGROUND: As with the increasing prevalence of loneliness among college students, it seems necessary to investigate the early grounds of its formation. Therefore, the present study was conducted to examine the relationship between attachment styles and loneliness through the mediating role of early maladaptive schemas (EMS).

METHODS: This research was correlational, of structural equations modeling (SEM) type. The statistical population included all the college students of the universities of Kermanshah in the academic year 2020-2021, of whom 338 were selected using convenience sampling. The measures used in this study included DiTomasso et al.'s social and emotional loneliness of adults, Hazan and Shaver's adult attachment, and Young's schema scales. For data analysis, Pearson's correlation coefficient and SEM were used in Lisrel 8.8 and SPSS-22 software.

RESULTS: The results illustrated that the hypothesized model of the study has a good fit in the studied sample. It was also found that both the avoidant and ambivalent attachment styles are related to loneliness through two EMS of disconnection-rejection and other-directedness.

CONCLUSIONS: Based on the findings, measures are recommended to increase information regarding the basic and underlying factors affecting loneliness for therapists and psychological specialists.}, } @article {pmid37102801, year = {2023}, author = {An, JS and Suh, KH}, title = {Relationship between Grateful Disposition and Subjective Happiness of Korean Young Adults: Focused on Double Mediating Effect of Social Support and Positive Interpretation.}, journal = {Behavioral sciences (Basel, Switzerland)}, volume = {13}, number = {4}, pages = {}, pmid = {37102801}, issn = {2076-328X}, abstract = {This study aimed to identify the relationship between grateful disposition and the subjective happiness of young adults; it examined a sequential double mediating effect model of social support and positive interpretation on this relationship. The study participants included 389 male and female Korean young adults. The Korean version of Gratitude Questionnaire-6, a modified subscale of the SU Mental Health Test, Iverson et al.'s scale for social support, and the Subjective Happiness Scale were used. PROCESS Macro 3.5 Model 6 was used to analyze the double mediating effect. The correlation analysis showed that grateful disposition was positively correlated with social support, positive interpretation, and subjective happiness in young adults. Moreover, social support was positively correlated with positive interpretation and subjective happiness, whereas positive interpretation was positively correlated with subjective happiness. In addition, the sequential mediating effect of social support and positive interpretation on grateful disposition and the subjective happiness of young adults was significant. This study confirmed the determinant roles of social support and positive interpretation in grateful disposition and the subjective happiness of young adults, providing useful information for planning future studies and developing education materials and interventions for cultivating grateful disposition in childhood and promoting happiness in young adults.}, } @article {pmid37094022, year = {2023}, author = {Kundu, N and Kumar, V and Nandi, D}, title = {Breakdown of dipole Born approximation and the role of Rydberg's predissociation for the electron-induced ion-pair dissociation to oxygen in the presence of background gases.}, journal = {The Journal of chemical physics}, volume = {158}, number = {15}, pages = {}, doi = {10.1063/5.0141973}, pmid = {37094022}, issn = {1089-7690}, abstract = {We study the electron-induced ion-pair dissociation to gas-phase oxygen molecules using a state-of-the-art velocity-map ion-imaging technique. The analysis is entirely based on the conical time-gated wedge-shaped velocity slice images of O-/O2 nascent anionic fragments, and the resulting observations are in favor of Van Brunt et al.'s report [R. J. Van Brunt and L. J. Kieffer, J. Chem. Phys. 60, 3057 (1974)]. A new image reconstruction method, Jacobian over parallel slicing, is introduced to overcome the drawback of ion exaggeration in determining the kinetic energy distribution from the time-gated parallel slicing technique, which offers an alternative approach to the wedge slicing method. Most importantly, the role of the quintet-heavy Rydberg state has been drawn out to the complex ion-pair formalism. The extracted kinetic energy and angular distributions from the wedge slice images reveal a high momentum transfer during the ion-pair dissociation process, which could be the finest rationale to observe the breakdown of dipole Born approximation driven by multipole moment associated with the incident electron beam. Three distinct dissociative momentum bands have been precisely identified for O- dissociation. However, radiationless Rydberg's predissociation continuum (≥15%) has become an inherent character of electron-induced ion-pair dissociation, which could be dealt with using the beyond Born-Oppenheimer treatment. The incoherent sum of Σ and Π symmetric-associated ion-pair final states has been precisely identified by modeling the angular distribution of O-/O2 for each of the kinetic energy bands. A negligibly small amount of forward-backward asymmetry is observed in the angular distribution of O-/O2, which might be explained by the dissociative state-specific quantum coherence mechanism as reported [Krishnakumar et al., Nat. Phys. 14, 149 (2018); Kumar et al., arXiv:2206.15024 (2022)] by Prabhudesai et al.}, } @article {pmid37089783, year = {2023}, author = {Steiner, A and Calò, F and Shucksmith, M}, title = {Rurality and social innovation processes and outcomes: A realist evaluation of rural social enterprise activities.}, journal = {Journal of rural studies}, volume = {99}, number = {}, pages = {284-292}, pmid = {37089783}, issn = {0743-0167}, support = {MR/L003287/1/MRC_/Medical Research Council/United Kingdom ; }, abstract = {Although increasingly prominent in research, policy and practice, little is known about social innovation in a rural context. To address this knowledge gap, our paper explores how rurality might affect the social innovation process. Drawing on 68 interviews carried out with beneficiaries, service providers and external stakeholders of a rural social enterprise initiative in Scotland, the paper adopts a realist evaluation theory (Pawson and Tilley, 1997) approach combined with Calò et al.'s (2019) social innovation analytical framework to identify Context-Mechanism-Outcome configurations for rural social innovation. The findings highlight that specific characteristics of rural places can act as stimuli of social innovation. Positive outcomes of a social innovation can potentially be rooted in rural peculiarity and its problematic context. Push factors, born out of necessity, lead to reactive social innovation and pull factors, derived through harnessing perceived opportunities in the environment, lead to proactive social innovation. Importantly, push factors do not undermine the establishment of social innovation - indeed, they can actually promote social innovation and strengthen its validity. The paper also shows that outcomes of the social innovation process might not be specific to rural areas. Instead, the pathway to the desired outcomes is conditioned by rural factors, shaping the contexts and mechanisms of rural social innovation. As different rural locations might have different resources to address local challenges, social innovation processes vary from one case to another, although the challenges being addressed might be similar. As such, rural social innovation policies should not be 'over prescribed'. Context creates both challenges and solutions and influences the type and form of mechanisms used to achieve a desirable social innovation outcome.}, } @article {pmid37087974, year = {2023}, author = {Casale, M and Somefun, O and Haupt Ronnie, G and Desmond, C and Sherr, L and Cluver, L}, title = {A conceptual framework and exploratory model for health and social intervention acceptability among African adolescents and youth.}, journal = {Social science & medicine (1982)}, volume = {326}, number = {}, pages = {115899}, doi = {10.1016/j.socscimed.2023.115899}, pmid = {37087974}, issn = {1873-5347}, mesh = {Adolescent ; Humans ; Africa ; *Black People ; Interdisciplinary Studies ; *Social Work ; *Health Promotion ; }, abstract = {Intervention acceptability has become an increasingly key consideration in the development, evaluation and implementation of health and social interventions. However, to date this area of investigation has been constrained by the absence of a consistent definition of acceptability, comprehensive conceptual frameworks disaggregating its components, and few reliable assessment measures. This paper aims to contribute to this gap, by proposing a conceptual framework and exploratory model for acceptability with a specific priority population for health and developmental interventions: adolescents and youth in Africa. We document our multi-staged approach to model development, comprising both inductive and deductive components, and both systematic and interpretative review methods. This included thematic analyses of respective acceptability definitions and findings, from 55 studies assessing acceptability of 60 interventions conducted with young people aged 10-24 in (mainly Southern and Eastern) Africa over a decade; a consideration of these findings in relation to Sekhon et al.'s Theoretical Framework of Acceptability (TFA); a cross-disciplinary review of acceptability definitions and models; a review of key health behavioural change models; and expert consultation with interdisciplinary researchers. Our proposed framework incorporates nine component constructs: affective attitude, intervention understanding, perceived positive effects, relevance, perceived social acceptability, burden, ethicality, perceived negative effects and self-efficacy. We discuss the rationale for the inclusion and definition of each component, highlighting key behavioural models that adopt similar constructs. We then extend this framework to develop an exploratory model for acceptability with young people, that links the framework components to each other and to intervention engagement. Acceptability is represented as an emergent property of a complex, adaptive system of interacting components, which can influence user engagement directly and indirectly, and in turn be influenced by user engagement. We discuss opportunities for applying and further refining or developing these models, and their value as a point of reference for the development of acceptability assessment tools.}, } @article {pmid37085508, year = {2023}, author = {Winter, K and Menne, NM and Bell, R and Buchner, A}, title = {Evaluating the impact of first-yes-counts instructions on eyewitness performance using the two-high threshold eyewitness identification model.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {6572}, pmid = {37085508}, issn = {2045-2322}, mesh = {Humans ; *Recognition, Psychology ; *Crime ; Police ; Probability ; Mental Recall ; }, abstract = {In eyewitness research, multiple identification decisions in sequential lineups are typically prevented by telling participants that only their first identification decision counts. These first-yes-counts instructions are incompatible with standard police protocols prescribing that witnesses shall see the entire lineup. Horry et al. were the first to experimentally test how this discrepancy between eyewitness research and standard police protocols affects eyewitness identification decisions. Here, the two-high threshold eyewitness identification model was used to disentangle the effect of the first-yes-counts instructions on the detection and guessing processes underlying eyewitness identification decisions. We report both a reanalysis of Horry et al.'s data and a conceptual replication. Both the reanalysis and the results of the conceptual replication confirm that first-yes-counts instructions do not affect the detection of the culprit but decrease the probability of guessing-based selections. To improve the ecological validity, research on sequential lineups should avoid first-yes-counts instructions.}, } @article {pmid37079838, year = {2023}, author = {Durán, JI and Fernández-Dols, JM}, title = {Basic emotions do not reliably co-occur with predicted facial expressions: Reply to Witkower et al. (2023).}, journal = {Emotion (Washington, D.C.)}, volume = {23}, number = {3}, pages = {908-910}, doi = {10.1037/emo0001227}, pmid = {37079838}, issn = {1931-1516}, mesh = {Humans ; *Facial Expression ; Emotions ; Anxiety ; Anxiety Disorders ; *Meditation ; }, abstract = {Replies to the comments made by Witkower, et al. (see record 2023-63008-004) on the current authors original article (see record 2022-03375-001). A core assumption of Basic Emotion Theory is that the conscious experience of a basic emotion co-occurs with a facial expression signal of that same emotion. Our analysis of available evidence found co-occurrence in only 13% of cases-thus calling into question basic and applied studies in which the emotion is inferred from the face. Our second analysis counted as a co-occurrence even when only part of the facial signal was observed. Co-occurrence was found in only 23% of cases. Witkower et al.'s rebuttal failed to undermine these important findings. They claimed that similar degrees of correlation are found in other areas of psychology, but they confuse co-occurrence of two intrinsic manifestations of the same event (expression and experience of emotion) with the correlation between one potential causal antecedent and an observed event (e.g., effects of meditation on anxiety). Our results stand as a major challenge to Basic Emotion Theory. (PsycInfo Database Record (c) 2023 APA, all rights reserved).}, } @article {pmid37079836, year = {2023}, author = {Murphy, BA and Dickens, LR}, title = {Authentic/hubristic pride controversies as a window on broader emotion measurement issues: Reply to Tracy et al. (2023).}, journal = {Emotion (Washington, D.C.)}, volume = {23}, number = {3}, pages = {899-902}, doi = {10.1037/emo0001197}, pmid = {37079836}, issn = {1931-1516}, support = {//John Templeton Foundation/ ; }, mesh = {Humans ; *Self Concept ; *Emotions ; }, abstract = {Replies to Tracy, et al. (see record 2023-63008-002) on the current authors' comments (see record 2023-63008-001) to Tracy, et al.'s original article (see record 2007-02840-009). In our conceptual and empirical review of the Authentic Pride (AP) and Hubristic Pride (HP) scales, we concluded that they do not validly assess a two-facet model of the emotion of pride. For instance, we concluded that the HP scale is not a measure of pride at all and suffers from other deficits (e.g., zero-inflated scores and lack of measurement precision), which make it unsuitable for use in most research. Yet, Tracy et al. raised insightful questions and counterpoints that show some of our arguments to be less dispositive than we had perceived them to be. In addition, some of the issues raised in this exchange speak to important issues in emotion assessment generally, some of which have thus far been inadequately discussed in the field of emotion research. We (a) highlight a few of the main areas of disagreement between us and Tracy et al., and (b) describe how these disagreements point to important issues in emotion assessment more broadly. (PsycInfo Database Record (c) 2023 APA, all rights reserved).}, } @article {pmid37070015, year = {2023}, author = {Campos, B and Sanchez Hernandez, H}, title = {Well-being: Strengthening and Broadening a Key Psychological Construct.}, journal = {Affective science}, volume = {4}, number = {1}, pages = {21-23}, pmid = {37070015}, issn = {2662-205X}, abstract = {Park et al.'s (2022) goal of bringing conceptual clarity to the study of psychological aspects of well-being is a good one. We consider their work in terms of its implications for moving towards an understanding of well-being that reflects the full spectrum of human experience, especially the experience of people who remain underrepresented, and poorly accounted for, in psychological science. In our view, there is reason to think that strengthening existing frameworks and broadening in terms of methodologies will be most productive for developing a comprehensive and inclusive understanding of well-being. We describe the distinct strength of the subjective well-being (SWB) construct for this purpose and offer two empirical examples that highlight the value of multiple measures and methods for understanding well-being. We suggest that continued use of the SWB measure, combined with state-of-the-art emotion measurement, and a mix of qualitative and quantitative methodologies be recommended as the way forward.}, } @article {pmid37070007, year = {2023}, author = {Willroth, EC}, title = {The Benefits and Challenges of a Unifying Conceptual Framework for Well-being Constructs.}, journal = {Affective science}, volume = {4}, number = {1}, pages = {41-44}, pmid = {37070007}, issn = {2662-205X}, support = {R00 AG071838/AG/NIA NIH HHS/United States ; }, abstract = {Centuries of philosophical debate and decades of empirical research have sought to characterize what it means to be psychologically well. A unifying conceptual framework to organize these diverse perspectives is needed to facilitate clear communication and cumulative science within the field of well-being science. Although a handful of overarching theoretical and measurement models of well-being have been proposed, they typically make strong claims about which constructs should be included or excluded as well as the manner and degree to which well-being constructs are related to one another. Thus, these models are often not widely adopted as organizational or communicative tools, due to their exclusion of particular theoretical perspectives or disagreement among researchers about the empirical structure of well-being. While the field continues to grapple with these issues, it would benefit from a unifying conceptual framework that is broad in scope and that can flexibly accommodate diverse theoretical perspectives and new empirical advances. In this paper, I discuss the benefits of a unifying conceptual framework for well-being, as well as the challenges in its construction. Specifically, I review strengths and limitations of Park et al.'s proposed framework of "emotional well-being," and suggest an alternative framework of "psychosocial well-being" that encompasses the diverse array of constructs that have been proposed as positive psychological aspects of well-being.}, } @article {pmid37067076, year = {2023}, author = {Nukui, K and Ishiai, S}, title = {Full-field input generated from right visual field information for healthy participants reproduces performance simulating left unilateral spatial neglect in line bisection.}, journal = {Journal of neuropsychology}, volume = {17}, number = {3}, pages = {505-520}, doi = {10.1111/jnp.12316}, pmid = {37067076}, issn = {1748-6653}, mesh = {Male ; Adult ; Humans ; Female ; Young Adult ; *Visual Fields ; Functional Laterality ; Healthy Volunteers ; *Perceptual Disorders ; Brain ; Space Perception ; }, abstract = {Patients with left unilateral spatial neglect (USN) typically place the subjective midpoint to the right of the objective centre when bisecting a horizontal line. This pathological phenomenon may be explained as a result of greater dependence on the right endpoint in the external reference frame (Koyama et al., Brain Cogn, 35, 1997, 271; McIntosh et al., Cogn Brain Res, 25, 2005, 833). Ishiai et al. (Brain, 112, 1989, 1485) reported that once patients with USN fixated on a certain point on the right part of the presented line, they persisted with this point and marked the subjective midpoint there without leftward searches. Ishiai et al.'s interpretation was that the patients saw a totalised line representation that extended equidistantly to the right and left sides, based on the information of the attended rightward extent from the subjective midpoint. Accordingly, we used virtual reality goggles (VRG) and devised a mirror-image viewing (MV) condition that showed a full-field view based on the right visual field information to test whether healthy participants would thereby show neglect-like bisection performance. The participants were 30 healthy adults (22-37 years old; 15 women and 15 men). In this condition, 96.7% (29/30) of participants were judged to exhibit USN-like performance of line bisection, indicating the effectiveness of MV condition to simulate USN. The novelty of the present study lies in the use of a task-specific intervention of neglect-like visuospatial processing during line bisection without attempting to modify the direction of spatial attention. This approach may contribute to the understanding of the pathological visuospatial processing of USN.}, } @article {pmid37063985, year = {2023}, author = {Latham, GP and Chen, X and Piccolo, RF and Itzchakov, G}, title = {An updated meta-analysis of the primed goal-organizational behaviour relationship.}, journal = {Royal Society open science}, volume = {10}, number = {4}, pages = {221494}, pmid = {37063985}, issn = {2054-5703}, abstract = {Environmental cues (e.g. achievement-related words and pictures) can prime/activate, in the absence of awareness, a mental representation of importance stored in memory. Chen et al.'s 2021 Applied Psychology: An International Review 70, 216-253. (doi:10.1111/apps.12239) meta-analysis revealed a moderate, significant overall effect for the goal priming-organizational behaviour relationship, with three moderators identified: context-specific versus a general prime, prime modality (i.e. visual versus linguistic) and experimental setting (field versus laboratory). An independent researcher found that their finding was negligibly affected by a publication bias. Shanks & Vadillo (2021), Royal Society Open Science 8, 210544. (doi:10.1098/rsos.210544) (field: k = 13, N = 683, d = 0.64), questioned Chen et al.'s conclusion regarding the effect size found in field studies (field: k = 8, N = 357, d = 0.68). In this paper, we discussed Shanks & Vadillo's selection of additional field experiments that led to their conclusion of a publication bias. We updated Chen et al.'s meta-analysis to include relevant studies conducted since that study's publication. The present meta-analysis reproduced the original findings in Chen et al. (field: k = 11, N = 534, d = 0.67). The updated findings are consistent with: (i) laboratory findings, (ii) the findings obtained in field experiments on consciously set goals and (iii) goal setting theory (Latham & Locke, 2018 In Handbook of industrial, work & organizational Psychology, vol. 1 (eds D Ones, N Anderson, C Viswesvaran, H Sinangil), pp. 103-124).}, } @article {pmid37063107, year = {2023}, author = {Thieffry, L and Olyff, G and Pioda, L and Detandt, S and Bazan, A}, title = {Running away from phonological ambiguity, we stumble upon our words: Laboratory induced slips show differences between highly and lowly defensive people.}, journal = {Frontiers in human neuroscience}, volume = {17}, number = {}, pages = {1033671}, pmid = {37063107}, issn = {1662-5161}, abstract = {INTRODUCTION: Freud proposed that slips of the tongue, including apparently simple ones, always have a sense and constitute « a half-success and a half-failure » compromise resulting from defensive mechanisms.

MATERIAL AND METHODS: A total of 55 subjects participated in a French adaptation of the Spoonerisms of Laboratory Induced Predisposition or SLIP-technique including 32 "neutral" and 32 taboo spoonerisms and measures of defensiveness. In accordance with a psychoanalytical and empirically supported distinction, we considered two kinds of defenses: elaborative or primary process and inhibitory or secondary process defenses, which were operationalized with the GeoCat and the Phonological-Nothing (PN) WordList, respectively. The GeoCat is a validated measure of primary process mentation and the PN WordList was shown to measure the defensive avoidance of language ambiguity.

RESULTS: Participants produced 37 slips, with no significant difference in the number of "neutral" and taboo slips. The GeoCat and the N/PN parameters explained 30% of the variance in the production of parapraxes, confirming the defensive logics of slips. When dividing the population into lowly and highly defensive participants (with the Marlowe Crowne Social Desirability scale), primary process mentation appears as a baseline default defense, but only highly defensive participants mobilize an additional inhibitory secondary process type of defense. Taking into account the a priori difference between taboo and "neutral" parapraxes, highly defensive participants made 2.7 times more taboo parapraxes than lowly defensive participants. However, if "neutral" parapraxes in both subgroups followed the same logic as the total group of parapraxes (significant contribution of primary process mentation in lowly defensives and of primary and secondary process mentation in highly defensives), these measures had no contribution to explain the occurrence of taboo parapraxes.

CONCLUSION: We propose that Motley et al.'s prearticulatory editor, ensuring the censorship over taboo parapraxes, is an external instance of inhibition, proximal to uttering, equivalent to the censorship between the systems Preconscious and Conscious in Freud's metapsychology. By contrast, the defenses measured in this research are internal, intimate control systems, probing for the censorship between the systems Unconscious and Preconscious, this is, for repression. This study contributes to support a psychodynamic explanatory model for the production of parapraxes.}, } @article {pmid37055758, year = {2023}, author = {Dean, L and Tolhurst, R and Nallo, G and Kollie, K and Bettee, A and Theobald, S}, title = {A health-systems journey towards more people-centred care: lessons from neglected tropical disease programme integration in Liberia.}, journal = {Health research policy and systems}, volume = {21}, number = {1}, pages = {29}, pmid = {37055758}, issn = {1478-4505}, support = {PO6407//Foreign and Commonwealth Office/ ; }, mesh = {Humans ; Liberia ; *Tropical Medicine ; Neglected Diseases/therapy ; }, abstract = {BACKGROUND: Neglected tropical diseases (NTDs) are associated with high levels of morbidity and disability as a result of stigma and social exclusion. To date, the management of NTDs has been largely biomedical. Consequently, ongoing policy and programme reform within the NTD community is demanding the development of more holistic disease management, disability and inclusion (DMDI) approaches. Simultaneously, integrated, people-centred health systems are increasingly viewed as essential to ensure the efficient, effective and sustainable attainment of Universal Health Coverage. Currently, there has been minimal consideration of the extent to which the development of holistic DMDI strategies are aligned to and can support the development of people-centred health systems. The Liberian NTD programme is at the forefront of trying to establish a more integrated, person-centred approach to the management of NTDs and provides a unique learning site for health systems decision makers to consider how shifts in vertical programme delivery can support overarching systems strengthening efforts that are designed to promote the attainment of health equity.

METHODS: We use a qualitative case study approach to explore how policy and programme reform of the NTD programme in Liberia supports systems change to enable the development of integrated people-centred services.

RESULTS: A cumulation of factors, catalysed by the shock to the health system presented by the Ebola epidemic, created a window of opportunity for policy change. However, programmatic change aimed at achieving person-centred practice was more challenging. Deep reliance on donor funding for health service delivery in Liberia limits the availability of flexible funding, and the ongoing funding prioritization towards specific disease conditions limits flexibility in health systems design that can shape more person-centred care.

CONCLUSION: Sheikh et al.'s four key aspects of people centred health systems, that is, (1) putting peoples voices and needs first; (2) people centredness in service delivery; (3) relationships matter: health systems as social institutions; and (4) values drive people centred health systems, enable the illumination of varying push and pull factors that can facilitate or hinder the alignment of DMDI interventions with the development of people-centred health systems to support disease programme integration and the attainment of health equity.}, } @article {pmid37053133, year = {2023}, author = {Hung, J and Chen, J and Chen, O}, title = {Are the relationships between mental health issues and being left-behind gendered in China: A systematic review and meta-analysis.}, journal = {PloS one}, volume = {18}, number = {4}, pages = {e0279278}, pmid = {37053133}, issn = {1932-6203}, mesh = {Male ; Child ; Female ; Humans ; *Mental Health ; *Suicide, Attempted ; Parents ; Suicidal Ideation ; China/epidemiology ; Randomized Controlled Trials as Topic ; }, abstract = {BACKGROUND: While most existing studies reveal left-behind children (LBC) are prone to suffering from mental health issues, some other literature fails to develop a statistical significance between being left-behind and facing mental health dilemmas. In further detail, it is noteworthy that suicide ideation is a gendered issue. Here girls, relative to their male counterparts, are more likely to experience emotional and affective challenges, alongside a higher risk of suicide ideation. Aside from suicide ideation, the rate of suicide attempts is also higher among Chinese female than among male LBC. However, Chang et al. counter-argue that, within the LBC cohorts, it is not statistically significant to state that girls were more likely for suicide attempts than boys.

METHODS: In this paper, a systematic review of relevant literature and a meta-analysis of all qualified randomised controlled trial (RCT) studies were conducted. The authors aim to examine all relevant studies with similar methodologies to observe the nuanced relationships between being left-behind and mental health issues in Chinese contexts. Specifically, the authors will, grounded on the findings from the systematic review and meta-analysis, assess whether the relationship between mental health issues and being left-behind is gendered in Chinese contexts by analysing all relevant findings derived from similar methodologies and the same method (i.e., RCT).

RESULTS: Aside from Wanjie et al.'s studies, it is noticeable that the rest of the studies share similar point estimates and their CIs overlapped to a large extent. As per the I2, given the presence of Wanjie et al.'s studies that demonstrate an observably higher degree of heterogeneity than the rest of the studies, the I2 values, each for the measurement of anxiety and depression, are 74.8 percent and 34.7 percent respectively. This shows that there is a considerable heterogeneity level for anxiety, while the heterogeneity level for depression is moderate. However, both p-values for the I2 statistics are larger than 0.05. Therefore, at the 0.05 significance level, it is statistically insignificant to reject the null hypothesis that there is no heterogeneity between individual studies in both the subgroups of anxiety and depression. Therefore, the concern of the potentially substantial heterogeneity should be irrelevant in this meta-analysis. Beyond the discussion from the forest plot, when looking at the single study addressing the relationship between being left-behind and having suicide attempts (note: LBC-OR is 1.22; 95 percent CI is 1.22 -and NLBC-OR is 1.42; 95 percent CI is 1.09-1.86 -at the p-value of 0.34), the findings demonstrate that such a relationship per se is not gendered at the 0.05 statistical significance level. However, when examining the relationship between being resilient and left-behind, such an association is gendered where the OR of female left-behind university students being resilient, relative to male left-behind university students, is slightly higher than that of female non-left-behind university students being resilient, relative to their male non-left-behind university student counterparts. It is noteworthy that this study focuses on studying left-behind and non-left-behind samples who entered universities. Since a raft of LBC are socially, educationally disadvantaged, they lack the opportunities to receive higher education. Therefore, the findings of this study might not be indicative of the LBC population at large.

CONCLUSIONS: While the findings of this meta-analysis project fail to reflect any gendered issues statistically, the authors are aware of the fact that the data included in this project were collected based on perception. Here samples, or their parents and teachers, were responsible for answering the questions with respect to samples' mental health status and demographic details. In China, especially in less developed rural regions, the discourse on mental health challenges might continue to be seen as taboo, so individuals giving responses might, consciously or not, tend to give socially desirable answers to avoid any potential social stigmatisation. Therefore, there is some extent of reservation regarding the validity of the included studies' data.}, } @article {pmid37049077, year = {2023}, author = {Shah, AW and Ha, SH and Siddique, JA and Kim, BH and Yoon, YO and Lim, HK and Kim, SK}, title = {Microstructure Evolution and Mechanical Properties of Al-Cu-Mg Alloys with Si Addition.}, journal = {Materials (Basel, Switzerland)}, volume = {16}, number = {7}, pages = {}, pmid = {37049077}, issn = {1996-1944}, support = {Materials & Components Technology Development Program (20011420)//The Ministry of Trade, Industry and Energy, South Korea/ ; }, abstract = {The aim of this study was to investigate the impact of the addition of a minor quantity of Si on the microstructure evolution, heat treatment response, and mechanical properties of the Al-4.5Cu-0.15Ti-3.0Mg alloy. The microstructure analysis of the base alloy revealed the presence of α-Al grains, eutectic α-Al-Al2CuMg (S) phases, and Mg32(Al, Cu)49 (T) phases within the Al grains. In contrast, the Si-added alloy featured the eutectic α-Al-Mg2Si phases, eutectic α-Al-S-Mg2Si, and Ti-Si-based intermetallic compounds in addition to the aforementioned phases. The study found that the Si-added alloy had a greater quantity of T phase in comparison to the base alloy, which was attributed to the promotion of T phase precipitation facilitated by the inclusion of Si. Additionally, Si facilitated the formation of S phase during aging treatment, thereby accelerating the precipitation-hardening response of the Si-added alloy. The as-cast temper of the base alloy displayed a yield strength of roughly 153 MPa, which increased to 170 MPa in the Si-added alloy. As a result of the aging treatment, both alloys exhibited a notable increase in tensile strength, which was ascribed to the precipitation of S phases. In the T6 temper, the base alloy exhibited a yield strength of 270 MPa, while the Si-added alloy exhibited a significantly higher yield strength of 324 MPa. This novel Si-added alloy demonstrated superior tensile properties compared to many commercially available high-Mg-added Al-Cu-Mg alloys, making it a potential replacement for such alloys in various applications within the aerospace and automotive industries.}, } @article {pmid37045076, year = {2023}, author = {Träff, U and Skagerlund, K and Östergren, R and Skagenholt, M}, title = {The importance of domain-specific number abilities and domain-general cognitive abilities for early arithmetic achievement and development.}, journal = {The British journal of educational psychology}, volume = {93}, number = {3}, pages = {825-841}, doi = {10.1111/bjep.12599}, pmid = {37045076}, issn = {2044-8279}, support = {721-2011-2872//Vetenskapsrådet/ ; }, mesh = {Male ; Child ; Humans ; Child, Preschool ; *Cognition ; *Problem Solving ; Memory, Short-Term ; Mathematics ; Achievement ; }, abstract = {BACKGROUND: Children's numerical and arithmetic skills differ greatly already at an early age. Although research focusing on accounting for these large individual differences clearly demonstrates that mathematical performance draws upon several cognitive abilities, our knowledge concerning key abilities underlying mathematical skill development is still limited.

AIMS: First, to identify key cognitive abilities contributing to children's development of early arithmetic skills. Second, to examine the extent to which early arithmetic performance and early arithmetic development rely on different or similar constellations of domain-specific number abilities and domain-general cognitive abilities.

SAMPLE: In all, 134 Swedish children (Mage  = 6 years and 4 months, SD = 3 months, 74 boys) participated in this study.

METHOD: Verbal and non-verbal logical reasoning, non-symbolic number comparison, counting knowledge, spatial processing, verbal working memory and arithmetic were assessed. Twelve months later, arithmetic skills were reassessed. A latent change score model was computed to determine whether any of the abilities accounted for variations in arithmetic development.

RESULTS: Arithmetic performance was supported by counting knowledge, verbal and non-verbal logical reasoning and spatial processing. Arithmetic skill development was only supported by spatial processing.

CONCLUSIONS: Results show that young children's early arithmetic performance and arithmetic development are supported by different cognitive processes. The findings regarding performance supported Fuchs et al.'s model (Dev Psychol, 46, 2010b, 1731) but the developmental findings did not. The developmental findings align partially to Geary et al.'s (J Educ Psychol, 109, 2017, 680) hypothesis stating that young children's early arithmetic development is more dependent on general cognitive abilities than number abilities.}, } @article {pmid37038031, year = {2023}, author = {Newman, PM and Qi, Y and Mou, W and McNamara, TP}, title = {Statistically Optimal Cue Integration During Human Spatial Navigation.}, journal = {Psychonomic bulletin & review}, volume = {30}, number = {5}, pages = {1621-1642}, pmid = {37038031}, issn = {1531-5320}, mesh = {Humans ; *Cues ; *Spatial Navigation ; Bayes Theorem ; }, abstract = {In 2007, Cheng and colleagues published their influential review wherein they analyzed the literature on spatial cue interaction during navigation through a Bayesian lens, and concluded that models of optimal cue integration often applied in psychophysical studies could explain cue interaction during navigation. Since then, numerous empirical investigations have been conducted to assess the degree to which human navigators are optimal when integrating multiple spatial cues during a variety of navigation-related tasks. In the current review, we discuss the literature on human cue integration during navigation that has been published since Cheng et al.'s original review. Evidence from most studies demonstrate optimal navigation behavior when humans are presented with multiple spatial cues. However, applications of optimal cue integration models vary in their underlying assumptions (e.g., uninformative priors and decision rules). Furthermore, cue integration behavior depends in part on the nature of the cues being integrated and the navigational task (e.g., homing versus non-home goal localization). We discuss the implications of these models and suggest directions for future research.}, } @article {pmid37035963, year = {2023}, author = {Timm, A and Kragelund Nielsen, K and Jensen, DM and Maindal, HT}, title = {Acceptability and adoption of the Face-it health promotion intervention targeting women with prior gestational diabetes and their partners: A qualitative study of the perspectives of healthcare professionals.}, journal = {Diabetic medicine : a journal of the British Diabetic Association}, volume = {40}, number = {7}, pages = {e15110}, doi = {10.1111/dme.15110}, pmid = {37035963}, issn = {1464-5491}, mesh = {Pregnancy ; Humans ; Female ; *Diabetes, Gestational/prevention & control ; *Diabetes Mellitus, Type 2/prevention & control ; Qualitative Research ; Health Personnel/psychology ; Health Promotion ; Delivery of Health Care ; }, abstract = {AIM: In this study, we investigated healthcare professionals' (HCPs) experiences with delivering home visits and digital coaching in the Face-it health promotion intervention targeting women with recent GDM and their families. Understanding the acceptability and adoption of a health promotion intervention can provide insights into intervention fidelity and future scalability.

METHODS: In total, 13 HCPs were interviewed. Data were analysed thematically through an abductive approach using Sekhon et al.'s theoretical framework of acceptability and Greenhalgh et al.'s framework for non-adoption, abandonment, scale-up, spread, and sustainability.

RESULTS: Acceptability and adoption of the intervention among HCPs were influenced by (1) skills and technology, (2) values, and (3) organisation. The intervention was experienced as acceptable to HCPs because the dialogue tool, visualising different topics, used in the home visits and digital coaching through the LIVA app were flexible and enabled them to address psychosocial health and personalise goal setting in families. However, delivering asynchronous and non-verbal communication was experienced as straining HCPs' relationship with families, which misaligned with HCPs' values. Establishing a non-judgemental environment was needed to increase intervention acceptability among HCPs towards addressing type 2 diabetes risk after GDM. Increased collaboration between HCPs may have aligned advice and support to families and could have benefitted delivery.

CONCLUSIONS: When delivering health promotion to women with prior GDM, flexible intervention components that support psychosocial- and mental health topics may increase acceptability and adoption of the intervention among HCPs. HCPs' skills, values, and organisational factors should be considered prior and during implementation.}, } @article {pmid37015195, year = {2023}, author = {Koopmans, M}, title = {Roughness as a Fractal Property in Univariate Time Series Data.}, journal = {Nonlinear dynamics, psychology, and life sciences}, volume = {27}, number = {2}, pages = {149-168}, pmid = {37015195}, issn = {1090-0578}, abstract = {In the analysis of time series data, roughness is sometimes seen as a distinct feature of fractality. This paper seeks to distinguish it from other aspects of that construct (self-affinity and long-range memory processes) and it examines the reliability of the roughness measures currently available, i.e., Gneiting et al.'s (2010) fractal dimension and Marmelat et al.'s (2012) relative roughness. The response of these estimators is evaluated to simulations at varying levels of persistence, as specified by the Hurst exponent, and to the presence or absence of short-range ARMA processes. Four empirical time series datasets are subjected to roughness estimation: the flow of the river Nile, daily recordings of the number of births to teens in the state of Texas, daily school attendance rates at an urban middle school, and unemployment figures provided by the US Department of Labor. Results from the simulation study indicate that persistence levels are faithfully reproduced by both estimation techniques, which also show the (dis)attenuating effects of the short-range dependencies. Analysis of the empirical data indicates that the fractal dimension works best for non-stationary data, while relative roughness is more suitable for stationary data. In the simulations as well as the empirical situation, both estimations reliably identify randomness, and are therefore recommended as goodness of fit measures when time series are analyzed.}, } @article {pmid37006534, year = {2023}, author = {Yu, X and Wu, R and Ji, Y and Feng, Z}, title = {Bibliometric and visual analysis of machine learning-based research in acute kidney injury worldwide.}, journal = {Frontiers in public health}, volume = {11}, number = {}, pages = {1136939}, pmid = {37006534}, issn = {2296-2565}, mesh = {Humans ; *Artificial Intelligence ; Machine Learning ; *Acute Kidney Injury ; Algorithms ; Bibliometrics ; }, abstract = {BACKGROUND: Acute kidney injury (AKI) is a serious clinical complication associated with adverse short-term and long-term outcomes. In recent years, with the rapid popularization of electronic health records and artificial intelligence machine learning technology, the detection rate and treatment of AKI have been greatly improved. At present, there are many studies in this field, and a large number of articles have been published, but we do not know much about the quality of research production in this field, as well as the focus and trend of current research.

METHODS: Based on the Web of Science Core Collection, studies reporting machine learning-based AKI research that were published from 2013 to 2022 were retrieved and collected after manual review. VOSviewer and other software were used for bibliometric visualization analysis, including publication trends, geographical distribution characteristics, journal distribution characteristics, author contributions, citations, funding source characteristics, and keyword clustering.

RESULTS: A total of 336 documents were analyzed. Since 2018, publications and citations have increased dramatically, with the United States (143) and China (101) as the main contributors. Regarding authors, Bihorac, A and Ozrazgat-Baslanti, T from the Kansas City Medical Center have published 10 articles. Regarding institutions, the University of California (18) had the most publications. Approximately 1/3 of the publications were published in Q1 and Q2 journals, of which Scientific Reports (19) was the most prolific journal. Tomašev et al.'s study that was published in 2019 has been widely cited by researchers. The results of cluster analysis of co-occurrence keywords suggest that the construction of AKI prediction model related to critical patients and sepsis patients is the research frontier, and XGBoost algorithm is also popular.

CONCLUSION: This study first provides an updated perspective on machine learning-based AKI research, which may be beneficial for subsequent researchers to choose suitable journals and collaborators and may provide a more convenient and in-depth understanding of the research basis, hotspots and frontiers.}, } @article {pmid37003773, year = {2023}, author = {Cabaleiro-Lago, EM and Fernández, B and Rodríguez-Fernández, R and Rodríguez-Otero, J and Vázquez, SA}, title = {Functional group corrections to the GFN2-xTB and PM6 semiempirical methods for noncovalent interactions in alkanes and alkenes.}, journal = {The Journal of chemical physics}, volume = {158}, number = {12}, pages = {124105}, doi = {10.1063/5.0140668}, pmid = {37003773}, issn = {1089-7690}, abstract = {Analytical corrections were developed to improve the accuracy of the PM6 and GFN2-xTB semiempirical quantum mechanical methods for the evaluation of noncovalent interaction energies in alkanes and alkenes. We followed the approach of functional group corrections, wherein the atom-atom pair corrections depend on the nature of the interacting functional groups. The training set includes 21 alkane and 13 alkene complexes taken from the Donchev et al.'s database [Sci. Data 8, 55 (2021)], with interaction energies calculated at the CCSD(T)/CBS level, and our own data obtained for medium-size complexes (of 100 and 112 atoms). In general, for the systems included in the training and validation sets, the errors obtained with the PM6-FGC and xTB-FGC methods are within the chemical accuracy.}, } @article {pmid37003194, year = {2023}, author = {Clay, S and Treloar, C and Degenhardt, L and Grebely, J and Christmass, M and Gough, C and Hayllar, J and McDonough, M and Henderson, C and Crawford, S and Farrell, M and Marshall, A}, title = {'I just thought that was the best thing for me to do at this point': Exploring patient experiences with depot buprenorphine and their motivations to discontinue.}, journal = {The International journal on drug policy}, volume = {115}, number = {}, pages = {104002}, doi = {10.1016/j.drugpo.2023.104002}, pmid = {37003194}, issn = {1873-4758}, mesh = {Humans ; Male ; Female ; Adult ; *Buprenorphine/therapeutic use ; Motivation ; Analgesics, Opioid/therapeutic use ; *Opioid-Related Disorders/drug therapy ; Opiate Substitution Treatment ; Patient Outcome Assessment ; }, abstract = {INTRODUCTION: Long-acting injectable depot buprenorphine is a recent addition to the suite of opioid agonist therapies (OAT) used to treat opioid use disorder (OUD). However, there has been little research that focuses on the lived experience of people receiving depot buprenorphine treatment and reasons for why people decide to discontinue. The aim of this study was to explore what it is like to receive depot buprenorphine and to understand the motivations behind why people discontinue.

METHODS: Open-ended, semi-structured interviews were conducted between November 2021 and January 2022 with individuals who were either currently receiving depot buprenorphine or had discontinued or were in the process of discontinuing depot buprenorphine. Liberati, et al.'s (2022) adaptation of Dixon-Woods's (2006) candidacy framework was used to analyse the participant experiences.

RESULTS: 40 participants (26 male, 13 female, 1 undisclosed; mean age 42 years) were interviewed about their experience with depot buprenorphine. At the time of the interview, 21 were currently receiving depot buprenorphine and 19 had discontinued this treatment or were in the process of discontinuing. Participants cited 4 key reasons why they decided to discontinue depot buprenorphine:1) feeling forced into the program, 2) experiencing negative side-effects, 3) finding the treatment ineffective, and 4) wanting to stop depot buprenorphine/OAT to use opioids again or feeling 'cured' and no longer in need of OAT. Participants were ultimately discussing issues related to clinician-patient power relations, agency and bodily autonomy, and the pursuit of well-being.

CONCLUSION: Depot buprenorphine remains a promising treatment for OUD and offers potential to improve treatment adherence. Instances of restricted OAT choice and consumer concerns regarding a lack of agency must be addressed in order to enhance therapeutic relationships. Clinicians and other healthcare workers in this field also need greater access to information about depot buprenorphine to better address issues patients face during treatment. More research is required to understand patient and treatment choice given the options of these new treatment formulations.}, } @article {pmid37002705, year = {2023}, author = {Kagan, D and Seear, K and Lenton, E and Farrugia, A and Valentine, K and Mulcahy, S and Fraser, S}, title = {The trouble with normalisation: Transformations to hepatitis C health care and stigma in an era of viral elimination.}, journal = {Sociology of health & illness}, volume = {45}, number = {7}, pages = {1421-1440}, doi = {10.1111/1467-9566.13638}, pmid = {37002705}, issn = {1467-9566}, mesh = {Humans ; Antiviral Agents/therapeutic use ; *Hepatitis C, Chronic/drug therapy ; Social Stigma ; Delivery of Health Care ; *Hepatitis C/drug therapy/diagnosis ; *Acquired Immunodeficiency Syndrome ; *HIV Infections/drug therapy/diagnosis ; }, abstract = {Modern health-care systems have customarily approached hepatitis C in ways that resemble the public health approach to HIV/AIDS known as 'HIV exceptionalism'. HIV exceptionalism describes the unusual emphasis on privacy, confidentiality and consent in approaches to HIV and was partly developed to address HIV/AIDS-related stigma. In the case of hepatitis C, exceptionalist approaches have included diagnosis and treatment by specialist physicians and other 'boutique' public health strategies. The recent availability of highly effective, direct-acting antivirals alongside goals to eliminate hepatitis C have heralded dramatic changes to hepatitis C health care, including calls for its 'normalisation'. The corollary to exceptionalism, normalisation aims to bring hepatitis C into routine, mainstream health care. This article draws on interviews with stakeholders (n = 30) who work with hepatitis C-affected communities in policy, community, legal and advocacy settings in Australia, alongside Fraser et al.'s (2017, International Journal of Drug Policy, 44, 192-201) theorisation of stigma, and Rosenbrock et al.'s (1999, The AIDS policy cycle in Western Europe: from exceptionalism to normalisation. WZB Discussion Paper, No. P 99-202) critique of normalisation to consider the perceived effects of hepatitis C normalisation. Stakeholders described normalisation as a stigma-reducing process. However, they also expressed concerns about the ongoing stigma and discrimination that is not ameliorated by normalisation. We suggest that in centring normalisation, changes in health care may exaggerate the power of technological solutions to transform the meanings of hepatitis C.}, } @article {pmid37002507, year = {2023}, author = {Arora, S and Brakey, HR and Jones, JL and Hood, N and Fuentes, JE and Cirolia, L}, title = {Project ECHO for Cancer Care: a Scoping Review of Provider Outcome Evaluations.}, journal = {Journal of cancer education : the official journal of the American Association for Cancer Education}, volume = {38}, number = {5}, pages = {1509-1521}, pmid = {37002507}, issn = {1543-0154}, support = {UL1 TR001449/TR/NCATS NIH HHS/United States ; }, mesh = {Humans ; *Outcome Assessment, Health Care ; Education, Medical, Continuing ; Data Collection ; *Neoplasms/diagnostic imaging/therapy ; }, abstract = {The Project ECHO model of telementoring has been used for the past 10 years to expand access to specialized cancer care. This scoping review identifies evidence for the model's ability to improve provider outcomes, synthesizing findings from existing studies within Moore et al.'s (2009) framework for continuing medical education outcomes. We search two large research databases and a collection maintained by Project ECHO staff for articles that focus on cancer ECHO programs, involve primary data collection, and were published between December 1, 2016, and November 30, 2021. We identified 25 articles for inclusion in our scoping review. Most articles reported results for outcomes related to program participation: attendance, satisfaction, and learning. Yet, just under half reported changes in provider practices. Results demonstrate widespread participation and improved learning resulting from ECHO programs focused on cancer care. There is also evidence of improved practices related to HCV vaccination and palliative care. We highlight examples of best practices as well as opportunities to improve provider outcome evaluations for cancer ECHO programs.}, } @article {pmid37002462, year = {2023}, author = {Landwehr, K}, title = {Sanford's L dissected: A partial replication and extension of Cai et al. (2017).}, journal = {Attention, perception & psychophysics}, volume = {85}, number = {4}, pages = {1304-1316}, pmid = {37002462}, issn = {1943-393X}, support = {LA 487/6-4//Deutsche Forschungsgemeinschaft/ ; }, mesh = {Humans ; *Optical Illusions/physiology ; Orientation ; Psychophysics ; Discrimination Learning ; Learning ; }, abstract = {Partial replications of experiments reported by Cai et al. (Attention, Perception, & Psychophysics, 79(4), 1217-1226, 2017) on the so-called Horizontal-vertical illusion confirmed that dissecting L-figures into two separate lines yields greater overestimation of (near-)verticals than do intact Ls. However, contrary to Cai et al.'s findings, which had been obtained with a staircase procedure, with the method of constant stimuli, the amount of illusion was much smaller. This divergence is explained by the self-reinforcing nature of adjustment procedures. Another finding, already reported by Cormack and Cormack (Perception & Psychophysics, 16(2), 208-212, 1974), that obtuse angles between an L's lines yield greater bias than acute angles, was also replicated in one experiment but tended to be reversed in another. Mixing dissected, upright and top-down inverted Ls and laterally oriented Ts, both with tilted lines, within one experiment confirmed that the bias for Ts is opposite to the one for Ls: For Ts, the effect of (virtual) bisection dominates, yielding an overestimation of the length of the undivided line, whereas for Ls, the horizontal-vertical anisotropy dominates, yielding an overestimation of the length of the vertical line. The differential gap effects can possibly be explained by interactions within the neural substrate between orientation-sensitive and end-inhibited neurons, and the method effects by perceptual learning.}, } @article {pmid37001277, year = {2023}, author = {Arroyos-Calvera, D and Covey, J and McDonald, R}, title = {Are distributional preferences for safety stable? A longitudinal analysis before and after the COVID-19 outbreak.}, journal = {Social science & medicine (1982)}, volume = {324}, number = {}, pages = {115855}, pmid = {37001277}, issn = {1873-5347}, mesh = {Humans ; *COVID-19/epidemiology ; Pandemics ; Health Policy ; Administrative Personnel ; Surveys and Questionnaires ; }, abstract = {Policy makers aim to respect public preferences when making trade-offs between policies, yet most estimates of the value of safety neglect individuals' preferences over how safety is distributed. Incorporating these preferences into policy first requires measuring them. Arroyos-Calvera et al. (2019) documented that people cared most about efficiency, but that equity followed closely, and self-interest mattered too, but not enough to override preferences for efficiency and equity. Early 2020 saw the outbreak of the COVID-19 pandemic. This event would impose major changes in how people perceived and experienced risk to life, creating an opportunity to test whether safety-related preferences are stable and robust to important contextual changes. Further developing Arroyos-Calvera et al.'s methodology and re-inviting an international general population sample of participants that had taken part in pre-pandemic online surveys in 2017 and 2018, we collected an April 2020 wave of the survey and showed that overall preferences for efficiency, equity and self-interest were remarkably stable before and after the pandemic outbreak. We hope this offers policy makers reassurance that once these preferences have been elicited from a representative sample of the population, they need not be re-estimated after important contextual changes.}, } @article {pmid36985281, year = {2023}, author = {Osório, N and Oliveira, V and Costa, MI and Santos-Costa, P and Serambeque, B and Gama, F and Adriano, D and Graveto, J and Parreira, P and Salgueiro-Oliveira, A}, title = {Short Peripheral Venous Catheters Contamination and the Dangers of Bloodstream Infection in Portugal: An Analytic Study.}, journal = {Microorganisms}, volume = {11}, number = {3}, pages = {}, pmid = {36985281}, issn = {2076-2607}, support = {024371//European Regional Development Fund (FEDER) through the Operational Program Competitiveness and Internationalization (PORTUGAL 2020)/ ; }, abstract = {Peripheral venous catheters (PVCs) are the most used vascular access devices in the world. However, failure rates remain considerably high, with complications such as PVC-related infections posing significant threats to patients' well-being. In Portugal, studies evaluating the contamination of these vascular medical devices and characterizing the associated microorganisms are scarce and lack insight into potential virulence factors. To address this gap, we analyzed 110 PVC tips collected in a large tertiary hospital in Portugal. Experiments followed Maki et al.'s semi-quantitative method for microbiological diagnosis. Staphylococcus spp. were subsequently studied for the antimicrobial susceptibility profile by disc diffusion method and based on the cefoxitin phenotype, were further classified into strains resistant to methicillin. Screening for the mecA gene was also done by a polymerase chain reaction and minimum inhibitory concentration (MIC)-vancomycin as determined by E-test, proteolytic and hemolytic activity on skimmed milk 1% plate and blood agar, respectively. The biofilm formation was evaluated on microplate reading through iodonitrotetrazolium chloride 95% (INT). Overall, 30% of PVCs were contaminated, and the most prevalent genus was Staphylococcus spp., 48.8%. This genus presented resistance to penicillin (91%), erythromycin (82%), ciprofloxacin (64%), and cefoxitin (59%). Thus, 59% of strains were considered resistant to methicillin; however, we detected the mecA gene in 82% of the isolates tested. Regarding the virulence factors, 36.4% presented α-hemolysis and 22.7% β-hemolysis, 63.6% presented a positive result for the production of proteases, and 63.6% presented a biofilm formation capacity. Nearly 36.4% were simultaneously resistant to methicillin and showed expression of proteases and/or hemolysins, biofilm formation, and the MIC to vancomycin were greater than 2 µg/mL. Conclusion: PVCs were mainly contaminated with Staphylococcus spp., with high pathogenicity and resistance to antibiotics. The production of virulence factors strengthens the attachment and the permanence to the catheter's lumen. Quality improvement initiatives are needed to mitigate such results and enhance the quality and safety of the care provided in this field.}, } @article {pmid36976537, year = {2023}, author = {Huang, HM and Huang, CY and Lin, KC and Yu, CH and Cheng, SF}, title = {Development and Psychometric Testing of the Clinical Reasoning Scale Among Nursing Students Enrolled in Three Types of Programs in Taiwan.}, journal = {The journal of nursing research : JNR}, volume = {31}, number = {2}, pages = {e263}, pmid = {36976537}, issn = {1948-965X}, mesh = {Humans ; *Clinical Competence ; Psychometrics ; *Students, Nursing ; Taiwan ; Reproducibility of Results ; Surveys and Questionnaires ; }, abstract = {BACKGROUND: There is no instrument currently available to assess the essential nursing competency of clinical reasoning (CR).

PURPOSE: The purpose of this study was to develop and test the psychometric properties of CR assessment instrument appropriate for use with nursing students across different types of programs.

METHODS: H. M. Huang et al.'s (2018) Framework of Competencies of Clinical Reasoning for Nursing Students was used to guide this study. Two rounds of Delphi study and confirmatory factor analysis (CFA) were conducted to test content and construct validity. Internal consistency was tested for reliability.

RESULTS: The four-domain, 16-item Likert-scale Clinical Reasoning Scale (CRS) was developed. One thousand five hundred four nursing students currently enrolled in three different types of nursing programs completed the CRS. The content validity index was .85-1.0, the CFA indicated goodness of fit, and the Cronbach's α score range was .78-.89.

CONCLUSION: The CRS is a valid and reliable tool for assessing CR in nursing students in different types of nursing program.}, } @article {pmid36959608, year = {2023}, author = {Yanful, B and Kirubarajan, A and Bhatia, D and Mishra, S and Allin, S and Di Ruggiero, E}, title = {Quality of care in the context of universal health coverage: a scoping review.}, journal = {Health research policy and systems}, volume = {21}, number = {1}, pages = {21}, pmid = {36959608}, issn = {1478-4505}, support = {407149/CAPMC/CIHR/Canada ; }, mesh = {Humans ; *Health Services ; Quality of Health Care ; *Universal Health Insurance ; }, abstract = {INTRODUCTION: Universal health coverage (UHC) is an emerging priority of health systems worldwide and central to Sustainable Development Goal 3 (target 3.8). Critical to the achievement of UHC, is quality of care. However, current evidence suggests that quality of care is suboptimal, particularly in low- and middle-income countries. The primary objective of this scoping review was to summarize the existing conceptual and empirical literature on quality of care within the context of UHC and identify knowledge gaps.

METHODS: We conducted a scoping review using the Arksey and O'Malley framework and further elaborated by Levac et al. and applied the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Extension for Scoping Reviews reporting guidelines. We systematically searched MEDLINE, EMBASE, CINAHL-Plus, PAIS Index, ProQuest and PsycINFO for reviews published between 1 January 1995 and 27 September 2021. Reviews were eligible for inclusion if the article had a central focus on UHC and discussed quality of care. We did not apply any country-based restrictions. All screening, data extraction and analyses were completed by two reviewers.

RESULTS: Of the 4128 database results, we included 45 studies that met the eligibility criteria, spanning multiple geographic regions. We synthesized and analysed our findings according to Kruk et al.'s conceptual framework for high-quality systems, including foundations, processes of care and quality impacts. Discussions of governance in relation to quality of care were discussed in a high number of studies. Studies that explored the efficiency of health systems and services were also highly represented in the included reviews. In contrast, we found that limited information was reported on health outcomes in relation to quality of care within the context of UHC. In addition, there was a global lack of evidence on measures of quality of care related to UHC, particularly country-specific measures and measures related to equity.

CONCLUSION: There is growing evidence on the relationship between quality of care and UHC, especially related to the governance and efficiency of healthcare services and systems. However, several knowledge gaps remain, particularly related to monitoring and evaluation, including of equity. Further research, evaluation and monitoring frameworks are required to strengthen the existing evidence base to improve UHC.}, } @article {pmid36951730, year = {2023}, author = {Awad, MN and Connors, EH}, title = {Active bystandership by youth in the digital era: Microintervention strategies for responding to social media-based microaggressions and cyberbullying.}, journal = {Psychological services}, volume = {20}, number = {3}, pages = {423-434}, pmid = {36951730}, issn = {1939-148X}, support = {K08 MH116119/MH/NIMH NIH HHS/United States ; T32 DA019426/DA/NIDA NIH HHS/United States ; UL1 TR001863/TR/NCATS NIH HHS/United States ; }, mesh = {Humans ; Adolescent ; Aggression/psychology ; *Cyberbullying/psychology ; Microaggression ; *Social Media ; Hostility ; }, abstract = {Microaggressions are intentional or unintentional slights, insults, invalidations, and offensive behaviors that communicate hostile or derogatory messages to minoritized populations. When microaggressions cross over to social media, they can be considered a form of cyberbullying, which occurs over digital devices and harms, threatens, undermines, or socially excludes others. Microaggressions and cyberbullying have adverse mental health outcomes for racial and cultural minority youth, and there is an urgent need for practical strategies youth can use online to interrupt and disarm negative and harmful social media content. We used a multimethod approach to critically appraise and adapt Sue et al.'s (2019) microinterventions framework for use on social media with youth bystanders. Our analysis found high compatibility between microinterventions and youth bystander research, supporting transferability to social media for use with youth. Relevant adaptations include incorporating strategies that promote cognitive appraisal, cognitive empathy, education via social media, and use of social media features for external support. Using a social media microaggression example for each of the four microinterventions, we provide concrete tactics and example social media posts that youth can use when they come across insulting or offensive commentary online. The resulting framework offers a promising set of theory and research-informed strategies ready for further testing and refinement. When validated and refined, these microinterventions could be used as stand-alone strategies and/or incorporated into existing cyberbullying prevention or media literacy programs. (PsycInfo Database Record (c) 2023 APA, all rights reserved).}, } @article {pmid36947387, year = {2023}, author = {Kaud, Y and McKeon, D and Lydon, S and O'Connor, P}, title = {Measuring and monitoring patient safety in hospitals in the Republic of Ireland.}, journal = {Irish journal of medical science}, volume = {192}, number = {6}, pages = {2581-2593}, pmid = {36947387}, issn = {1863-4362}, mesh = {Humans ; Ireland ; *Patient Safety ; Reproducibility of Results ; *Hospitals ; Qualitative Research ; }, abstract = {BACKGROUND: Measuring and monitoring safety (MMS) is critical to the success of safety improvement efforts in healthcare. However, a major challenge to improving safety is the lack of high quality information to support performance evaluation.

AIMS: The aim of this study was to use Vincent et al.'s MMS framework to evaluate the methods used to MMS in Irish hospitals and make recommendations for improvement.

METHODS: The first phase of this qualitative study used document analysis to review national guidance on MMS in Ireland. The second phase consisted of semi-structured interviews with key stakeholders on their understanding of MMS. The MMS framework was used to classify the methods identified.

RESULTS: Six documents were included for analysis, and 24 semi-structured interviews were conducted with key stakeholders working in the Irish healthcare system. A total of 162 methods of MMS were identified, with one method of MMS addressing two dimensions. Of these MMS methods, 30 (18.4%) were concerned with past harm, 40 (24.5%) were concerned with the reliability of safety critical processes, 16 (9.8%) were concerned with sensitivity to operations, 28 (17.2%) were concerned with anticipation and preparedness, and 49 (30%) were concerned with integration and learning.

CONCLUSIONS: There are a wide range of methods of MMS in Irish hospitals. It is suggested that there is a need to identify those methods of MMS that are particularly useful in reducing harm and supporting action and improvement and do not place a large burden on healthcare staff to either use or interpret.}, } @article {pmid36931832, year = {2023}, author = {Fragaszy, DM}, title = {Adaptable navigation in bull ants (Myrmecia midas).}, journal = {Journal of comparative psychology (Washington, D.C. : 1983)}, volume = {137}, number = {1}, pages = {1-3}, doi = {10.1037/com0000343}, pmid = {36931832}, issn = {1939-2087}, mesh = {Animals ; *Ants/physiology ; Learning ; }, abstract = {In an early scientific description of navigation (finding one's way from a known location to a known destination) in an arthropod, Charles Turner, one of comparative psychology's staunchest early proponents of studying individual variation. The field of comparative psychology has caught up with Charles Turner. In this essay, the author presents an overview of the results of previous studies which suggest that several species of ants use vision effectively to navigate in three dimensions, in daylight, and in darkness. Bull ants, a species that navigates in dim light, have large compound eyes containing receptors that are sensitive to ultraviolet (UV), blue, and green regions of the electromagnetic spectrum. Islam et al.'s findings illustrate a very general point about behavior that comparative psychologists do (and should continue to) take seriously, theoretically, and empirically. When we take the time to look closely, the behavior of individuals varies in biologically and psychologically important ways, no matter the size of their bodies or nervous systems. The adaptability of individuals arises from variation within the individual over time, manifest in this study as the adoption of novel routes as circumstances required. The adaptability of populations arises from variation across individuals, evident in this study in ants that learned to travel directly to the edge of the barrier and ants that learned to travel directly to the barrier, then make a right-angle turn to travel along it to an edge. The sources and consequences of behavioral variability, within and across individuals, and its manifestations across species, must remain core concerns for comparative psychology, as they were for Charles Turner more than 100 years ago. (PsycInfo Database Record (c) 2023 APA, all rights reserved).}, } @article {pmid36931503, year = {2023}, author = {Beckers, G and Manon, J and Lejeune, G and Gläser, M and Kaminski, L and Cornu, O and Van Cauter, M}, title = {How to avoid systematic postoperative blood test after total hip arthroplasty: A new risk scoring system compared to Wu's score.}, journal = {Orthopaedics & traumatology, surgery & research : OTSR}, volume = {109}, number = {7}, pages = {103597}, doi = {10.1016/j.otsr.2023.103597}, pmid = {36931503}, issn = {1877-0568}, mesh = {Humans ; Female ; *Arthroplasty, Replacement, Hip/adverse effects ; Retrospective Studies ; Case-Control Studies ; *Arthroplasty, Replacement, Knee/adverse effects ; Risk Factors ; Hematologic Tests ; }, abstract = {BACKGROUND: Routine laboratory studies are often performed following total hip arthroplasty (THA). However, lately, their necessity has been challenged and risk factors for postoperative transfusion are still debated. Recently, a risk scoring system to single out patients that should have a postoperative blood test has been published by Wu et al. The purposes of this retrospective study were: (1) to validate this recently published risk scoring system to identify patients who should have a postoperative laboratory test; (2) to single out risk factors of postoperative transfusion; (3) to determine if another score can more accurately predict the need for postoperative transfusion.

HYPOTHESIS: Wu et al.'s risk scoring system can accurately identify patients who should have a postoperative blood test.

METHODS: In all, 1693 patients who underwent primary THAs between June 2015 and October 2020 were screened for potential eligibility to include 1000 patient for analysis. Preoperative and postoperative blood tests were done for every patient. Clinical information and laboratory results were retrospectively collected and analyzed. A descriptive analysis followed by univariate and multivariate analysis were sequentially performed. A multiple logistic regression model was employed to determine a formula predicting the transfusion risk called THABUS for Total Hip Arthroplasty Blood test Usefulness Score. The risk scoring system for complete blood count published by Wu et al. in may 2020 was performed for every patient and compared to the THABUS predictive model.

RESULTS: The transfusion rate was 2.3% (23/1000). The risk-scoring system published by Wu and al. showed that a laboratory test was necessary for 60.6% (606/1000) however 13% (3/23) of the patients who needed a blood transfusion were missed by the risk-scoring system, giving it a sensitivity of 86.95% and a specificity of 40%. Increasing age, arterial hypertension, female gender, low preoperative hemoglobin, ASA score≥2 and diagnosis of osteonecrosis of the femoral head were significantly associated with postoperative transfusion. The THABUS formula can predict the risk for transfusion with a sensibility of 96.65% and a specificity of 75.54%. In our cohort of 1000 patients, following the THABUS formula would have led to 261 postoperative blood test and cost savings of 32,132$. Only one patient (4.3%) was missed by our new score. The THABUS formula is significantly better than Wu et al.'s complete blood count score in identifying both patient that will need a transfusion (p<0.01) and those who shouldn't have a postoperative blood test (p<0.001). Medical intervention because of creatinine or electrolytes abnormality was needed in 0.3% (3/1000) of patients.

DISCUSSION: In this study Wu et al.'s recently published complete blood count risk-scoring system was not validated. However, in the studied population the THABUS formula can accurately target patients who might need a transfusion. The use of the THABUS formula could reduce hospitalization costs without compromising the patients' safety.

LEVEL OF EVIDENCE: III, case-control study.}, } @article {pmid36928224, year = {2023}, author = {Eshtiaghi, A and Margolin, E and Micieli, JA}, title = {Inaccuracy of idiopathic intracranial hypertension diagnosis in case reports.}, journal = {Eye (London, England)}, volume = {37}, number = {15}, pages = {3243-3248}, pmid = {36928224}, issn = {1476-5454}, mesh = {Humans ; *Pseudotumor Cerebri/complications ; *Papilledema/diagnosis/etiology ; Neuroimaging ; }, abstract = {BACKGROUND: We reviewed the medical case report literature to determine the proportion of cases of idiopathic intracranial hypertension (IIH) that were either inappropriately labelled as IIH or prematurely given this diagnosis.

METHODS: We searched OVID MEDLINE from 2012 to 2022 to identify case reports that diagnosed patients with IIH. Case reports were assessed for diagnostic accuracy using Friedman et al.'s revised diagnostic criteria for primary pseudotumor cerebri syndrome. Our primary outcome was the crude prevalence of inappropriate or premature IIH diagnoses. Our secondary outcome was determining if inaccurate IIH diagnoses were associated with variables such as journal subscription model and impact factor, author affiliation, country of origin, and year of publication.

RESULTS: A total of 33/185 case reports (17.8%) either incorrectly labelled a patient as having IIH or did not perform all of the investigations necessary to make a diagnosis of IIH. Some of these studies (4.8%) were believed to still represent 'probable' IIH given the clinical presentation, whereas 13.0% of studies were determined to have mislabelled their patients as having IIH. The most common reason that case reports did not meet diagnostic criteria included: a lack of MRV in atypical patient cases (42.4%, n = 14), no papilledema in addition to a lack of characteristic neuroimaging features (33.3%, n = 11), intracranial hypertension being secondary to another documented cause (12.1%, n = 4), normal LP opening pressure in addition to other factors (12.1%,n = 4), no description of neuroimaging (6.1%, n = 2), and abnormal CSF composition (6.1%, n = 2). Case reports that used the term 'IIH' incorrectly had a significantly lower journal impact factor (2.0 vs. 2.6, p = 0.01).

CONCLUSIONS: There is a high prevalence of premature or inappropriate diagnoses of IIH in the peer-reviewed case report literature. Adherence to published diagnostic criteria is needed when publishing IIH case reports, and authors are expected to report all relevant data in their report to ensure that an accurate diagnosis is made.}, } @article {pmid36925350, year = {2023}, author = {Golcuk, Y and Golcuk, BK}, title = {Importance of nutritional assessment in evaluating patients with chemotherapy-induced febrile neutropenia: Insights from Heo et al.'s study and future implications.}, journal = {The American journal of emergency medicine}, volume = {67}, number = {}, pages = {183-184}, doi = {10.1016/j.ajem.2023.03.007}, pmid = {36925350}, issn = {1532-8171}, mesh = {Humans ; *Chemotherapy-Induced Febrile Neutropenia ; Nutrition Assessment ; *Febrile Neutropenia/chemically induced ; Antineoplastic Combined Chemotherapy Protocols ; Granulocyte Colony-Stimulating Factor ; }, } @article {pmid36918620, year = {2023}, author = {van Schie, K and Fawcett, JM and Anderson, MC}, title = {On the role of inhibition in suppression-induced forgetting.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {4242}, pmid = {36918620}, issn = {2045-2322}, support = {MC_UU_00030/1/MRC_/Medical Research Council/United Kingdom ; MC- A060-5PR00/MRC_/Medical Research Council/United Kingdom ; }, mesh = {*Mental Recall/physiology ; *Cues ; Inhibition, Psychological ; }, abstract = {Suppressing retrieval of unwanted memories can cause forgetting, an outcome often attributed to the recruitment of inhibitory control. This suppression-induced forgetting (SIF) generalizes to different cues used to test the suppressed content (cue-independence), a property taken as consistent with inhibition. But does cue-independent forgetting necessarily imply that a memory has been inhibited? Tomlinson et al. (Proc Natl Acad Sci 106:15588-15593, 2009) reported a surprising finding that pressing a button also led to cue-independent forgetting, which was taken as support for an alternative interference account. Here we investigated the role of inhibition in forgetting due to retrieval suppression and pressing buttons. We modified Tomlinson et al.'s procedure to examine an unusual feature they introduced that may have caused memory inhibition effects in their experiment: the omission of explicit task-cues. When tasks were uncued, we replicated the button-press forgetting effect; but when cued, pressing buttons caused no forgetting. Moreover, button-press forgetting partially reflects output-interference effects at test and not a lasting effect of interference. In contrast, SIF occurred regardless of these procedural changes. Collectively, these findings indicate that simply pressing a button does not induce forgetting, on its own, without confounding factors that introduce inhibition into the task and that inhibition likely underlies SIF.}, } @article {pmid36909012, year = {2023}, author = {Bampi, H and Barberi, M and Lima-Ribeiro, MS}, title = {Kill site database: A unified dataset on human-megafauna interactions across time and space.}, journal = {Data in brief}, volume = {47}, number = {}, pages = {108998}, pmid = {36909012}, issn = {2352-3409}, abstract = {The database presented in this data article is related to the paper "Megafauna kill sites in South America: a critical review" [1]. It includes a list of 134 publications on human-megafauna interaction, with 69 archaeological sites showing human-megafauna interaction. From these sites, 44 present a minimum human-megafauna association, from which up to 17 megafauna kill sites were classified, with up to 15 exploited extinct megafauna taxa. It also provides a list of current taxonomic classifications of extinct megafauna that humans have exploited according to empirical evidence presented in the related paper. The megafauna kill sites were classified based on five restrictive criteria according to Grayson and Meltzer's (2015, 2002), Borrero's (2009) and Mothé et al.'s (2020) protocol. The kill sites database reflects the empirical evidence on megafauna exploitation by humans available in scientific literature and is useful to understand the human-megafauna interactions in the late Quaternary. Finally, we also provide our online repository (www.killsitedatabase.com), an initiative to unify the evidence on megafauna kill sites (and their related data) worldwide, starting in South America.}, } @article {pmid36908585, year = {2023}, author = {Pietersen, PI and Lynggård Bo Madsen, J and Asmussen, J and Lund, L and Nielsen, TK and Pedersen, M and Engvad, B and Graumann, O}, title = {Multiparametric magnetic resonance imaging for characterizing renal tumors: A validation study of the algorithm presented by Cornelis et al.}, journal = {Journal of clinical imaging science}, volume = {13}, number = {}, pages = {7}, pmid = {36908585}, issn = {2156-7514}, abstract = {OBJECTIVES: In the last decade, the incidence of renal cell carcinoma (RCC) has been rising, with the greatest increase observed for solid tumors. Magnetic resonance imaging (MRI) protocols and algorithms have recently been available for classifying RCC subtypes and benign subtypes. The objective of this study was to prospectively validate the MRI algorithm presented by Cornelis et al. for RCC classification.

MATERIAL AND METHODS: Over a 7-month period, 38 patients with 44 renal tumors were prospectively included in the study and received an MRI examination in addition to the conventional investigation program. The MRI sequences were: T2-weighted, dual chemical shift MRI, diffusion-weighted imaging (DWI), and dynamic contrast-enhanced T1-weighted in wash-in and wash-out phases. The images were evaluated according to the algorithm by two experienced, blinded radiologists, and the histopathological diagnosis served as the gold standard.

RESULTS: Of 44 tumors in 38 patients, only 8 tumors (18.2%) received the same MRI diagnosis according to the algorithm as the histopathological diagnosis. MRI diagnosed 16 angiomyolipoma, 14 clear cell RCC (ccRCC), 12 chromophobe RCC (chRCC), and two papillary RCC (pRCC), while histopathological examination diagnosed 24 ccRCC, four pRCC, one chRCC, and one mixed tumor of both pRCC and chRCC. Malignant tumors were statistically significantly larger than the benign (3.16 ± 1.34 cm vs. 2.00 ± 1.04 cm, P = 0.006).

CONCLUSION: This prospective study could not reproduce Cornelis et al.'s results and does not support differentiating renal masses using multiparametric MRI without percutaneous biopsy in the future. The MRI algorithm showed few promising results to categorize renal tumors, indicating histopathology for clinical decisions and follow-up regimes of renal masses are still required.}, } @article {pmid36898944, year = {2023}, author = {Bravi, CA and Mottrie, A}, title = {Reply to Luca Sarchi, Maria Chiara Sighinolfi, Simone Assumma, et al.'s Letter to Editor re: Carlo A. Bravi, Marco Paciotti, Eleonora Balestrazzi, et al. Outcomes of Robot-assisted Radical Prostatectomy with the Hugo RAS Surgical System: Initial Experience at a High-volume Robotic Center. Eur Urol Focus. In press. https://doi.org/10.1016/j.euf.2023.01.008.}, journal = {European urology focus}, volume = {9}, number = {5}, pages = {843}, doi = {10.1016/j.euf.2023.03.002}, pmid = {36898944}, issn = {2405-4569}, mesh = {Male ; Humans ; *Robotic Surgical Procedures ; *Robotics ; Prostate ; Prostatectomy ; Seminal Vesicles ; }, } @article {pmid36898603, year = {2023}, author = {Youngstrom, EA}, title = {Editorial: Adding Measures of Emotion Dysregulation to Our Toolkits.}, journal = {Journal of the American Academy of Child and Adolescent Psychiatry}, volume = {62}, number = {7}, pages = {716-717}, doi = {10.1016/j.jaac.2023.03.003}, pmid = {36898603}, issn = {1527-5418}, mesh = {Adolescent ; Child ; Humans ; *Emotions/physiology ; *Irritable Mood ; Learning ; Psychopathology ; Surveys and Questionnaires ; Systematic Reviews as Topic ; }, abstract = {Emotion dysregulation is at the heart of our work with families. Learning to recognize and regulate emotions is among the most important developmental tasks. Culturally inappropriate displays of emotion are a major driver of clinical referrals for externalizing problems, but ineffective and maladaptive emotion regulation also contributes to internalizing problems; in fact, emotion dysregulation is central to most psychopathology. Given its ubiquity and importance, it is perhaps surprising that there have not been well-known and well-validated options for assessing it. That is changing. Freitag and Grassie et al.[1] conducted a systematic review of emotion dysregulation questionnaires in children and adolescents. Searching 3 databases, they scanned more than 2,000 articles, retaining more than 500 in their review, capturing 115 different instruments. They found an 8-fold increase in published research comparing the first and second decades of this millennium, and a quadrupling of the number of measures available from 30 to 115.[2] A recent narrative review by Althoff and Ametti[3] of measures of irritability and dysregulation included several neighboring scales outside the scope of Freitag and Grassie et al.'s review.[1].}, } @article {pmid36898316, year = {2023}, author = {Scheidegger, A and Blättler, LT and Gubler, DA and Penedo, JMG and Aybek, S and Bischoff, N and Egloff, N and Grosse Holtforth, M}, title = {War experiences and relationship problems predict pain sensitivity cross-sectionally among patients with chronic primary pain.}, journal = {Journal of psychosomatic research}, volume = {168}, number = {}, pages = {111209}, doi = {10.1016/j.jpsychores.2023.111209}, pmid = {36898316}, issn = {1879-1360}, mesh = {Humans ; *Chronic Pain/psychology ; Pain Measurement ; }, abstract = {BACKGROUND: Most patients suffering from chronic pain are more susceptible to pain and pressure due to higher pain sensitivity. Since psychosocial factors play a central role in developing and maintaining chronic pain, investigating associations between pain sensitivity and psychosocial stressors promises to advance the biopsychosocial understanding of chronic pain.

OBJECTIVES: We aimed to replicate Studer et al.'s (2016) findings about associations of psychosocial stressors with pain sensitivity in a new sample of patients with chronic primary pain (ICD-11, MG30.0).

METHODS: A pain provocation test was used on both middle fingers and earlobes to assess pain sensitivity among 460 inpatients with chronic primary pain. Potentially life-threatening accidents, war experiences, relationship problems, certified inability to work, and adverse childhood experiences were assessed as potential psychosocial stressors. Structural equation modeling was used to investigate associations between psychosocial stressors and pain sensitivity.

RESULTS: We partially replicated Studer et al.'s findings. Similar to the original study, patients with chronic primary pain showed enhanced pain sensitivity values. Within the investigated group, war experiences (β = 0.160, p < .001) and relationship problems (β = 0.096, p = .014) were associated with higher pain sensitivity. In addition, the control variables of age, sex, and pain intensity also showed a predictive value for higher pain sensitivity. Unlike Studer et al., we could not identify a certified inability to work as a predictor of higher pain sensitivity.

CONCLUSIONS: This study showed that beyond age, sex, and pain intensity, the psychosocial stressors of war experiences and relationship problems were associated with higher pain sensitivity.}, } @article {pmid36871963, year = {2023}, author = {Adams Nejatbakhsh, N and Dawson, D and Hutchison, M and Selby, P}, title = {Association between pediatric TBI and mental health and substance use disorders: A scoping review.}, journal = {Brain injury}, volume = {37}, number = {6}, pages = {525-533}, doi = {10.1080/02699052.2023.2184871}, pmid = {36871963}, issn = {1362-301X}, mesh = {Adolescent ; Child ; Humans ; Mental Health ; Cross-Sectional Studies ; Longitudinal Studies ; Prospective Studies ; *Brain Injuries, Traumatic/complications/epidemiology ; *Mental Disorders/epidemiology/etiology ; *Substance-Related Disorders/epidemiology ; }, abstract = {BACKGROUND: The relationship between pediatric Traumatic Brain Injury (TBI) and long-term mental health and substance use disorders is not well known, resulting in inadequate prevention and management strategies. The aim of this scoping review is to review the evidence on pediatric TBI and the development of mental health disorders and substance use later in life and to identify gaps in the literature to inform future research.

METHODS: We searched multiple databases for original articles published between September 2002 and September 2022 on TBI-related mental health and/or substance use disorders in children and youth. Two independent reviewers performed the screening using Arksey and O'Malley and Levac et al.'s scoping review framework.

RESULTS: A total of six papers are included in this scoping review. Studies included are comprised of cross-sectional and prospective longitudinal cohort studies.

DISCUSSION: A correlation between pediatric TBI and development of certain mental health disorders and substance use is suggested, although much of the current evidence is mixed and does not account for confounding variables. Future studies should aim to closely examine these links and identify modifiers that can influence these relationships.}, } @article {pmid39086850, year = {2023}, author = {Cao, W and Li, Y and Yu, Q}, title = {Sensitivity analysis for assumptions of general mediation analysis.}, journal = {Communications in statistics: Simulation and computation}, volume = {52}, number = {6}, pages = {2453-2470}, pmid = {39086850}, issn = {0361-0918}, support = {P42 ES013648/ES/NIEHS NIH HHS/United States ; R01 CA275089/CA/NCI NIH HHS/United States ; R15 MD012387/MD/NIMHD NIH HHS/United States ; }, abstract = {Mediation analysis is widely used to identify significant mediators and estimate the mediation (direct and indirect) effects in causal pathways between an exposure variable and a response variable. In mediation analysis, the mediation effect refers to the effect transmitted by mediator intervening the relationship between an exposure variable and a response variable. Traditional mediation analysis methods, such as the difference in the coefficient method, the product of the coefficient method, and counterfactual framework method, all require several key assumptions. Thus, the estimation of mediation effects can be biased when one or more assumptions are violated. In addition to the traditional mediation analysis methods, Yu et al. proposed a general mediation analysis method that can use general predictive models to estimate mediation effects of any types of exposure variable(s), mediators and outcome(s). However, whether this method relies on the assumptions for the traditional mediation analysis methods is unknown. In this paper, we perform series of simulation studies to investigate the impact of violation of assumptions on the estimation of mediation effects using Yu et al.'s mediation analysis method. We use the R package mma for all estimations. We find that three assumptions for traditional mediation analysis methods are also essential for Yu et al.'s method. This paper provides a pipeline for using simulations to evaluate the impact of the assumptions for the general mediation analysis.}, } @article {pmid38625196, year = {2023}, author = {Mossberger, K and Martini, NF and McCullough, M and Tolbert, CJ}, title = {Digital economic activity and resilience for metros and small businesses during Covid-19.}, journal = {Small business economics}, volume = {60}, number = {4}, pages = {1699-1717}, pmid = {38625196}, issn = {1573-0913}, abstract = {UNLABELLED: The Covid-19 pandemic had an unequal impact across businesses and communities and rapidly accelerated digital trends in the economy. What role, then, did website use play in community resilience and small business outcomes? This article examines a new source of population data on domain name hosts to provide a unique measure of digital economic activity within communities. Seventy-five percent are commercial, including online-only, brick-and-mortar, small, and microbusinesses. With geolocated data on 20 million US domain name hosts, we investigate how their density (per 100 people) affected economic outcomes in the nation's largest metros during the pandemic. Using monthly time series data for the 50 largest metropolitan areas, the domain host data is merged with the US Census Small Business Pulse Surveys and Chetty et al.'s Opportunity Insights data. Results indicate metros with higher concentrations of businesses with an online presence experienced more positive economic perceptions and outcomes from April to December 2020. This high-frequency, granular data on digital economic activity suggests that digitally enabled small and microbusinesses played an important role in local economic resilience and demonstrates how commercial data can be used to generate new insights in a fast-changing environment.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11187-022-00674-x.}, } @article {pmid38549784, year = {2023}, author = {Matchin, W}, title = {Lexico-semantics obscures lexical syntax.}, journal = {Frontiers in language sciences}, volume = {2}, number = {}, pages = {}, pmid = {38549784}, issn = {2813-4605}, support = {P50 DC014664/DC/NIDCD NIH HHS/United States ; }, abstract = {A recently emerging generalization about language and the brain is that brain regions implicated in language that show syntax-related activations (e.g., increased activation for more complex sentence structures) also tend to show word-related activations, such as increased activation to reading real words (e.g. RAIN) relative to pseudowords (e.g. PHREZ) (Fedorenko et al., 2016). Fedorenko et al., (2020) generalize as follows: "…syntactic/combinatorial processing is not separable from lexico-semantic processing at the level of brain regions-or even voxel subsets-within the language network". Based on this generalization, Fedorenko et al. have made the conclusion "…that a cognitive architecture whereby syntactic processing is not separable from the processing of individual word meanings is most likely", arguing against "syntax-centric" views of language as promulgated by Chomsky and others. However, the notion of "lexico-semantics" articulated here obscures the fact that words are both syntactic and semantic entities. Because of this, any functional neuroimaging experiment that manipulates lexicality will almost assuredly tax both syntactic and semantic resources, and is therefore inadequate for isolating conceptual-semantic processing in the brain in exclusion to syntax. In addition, Fedorenko et al. do not satisfactorily account for robust lesion data that shows clear functional-anatomical dissociations within the language network. Finally, a "syntax-centric" view of language is perfectly compatible with Fedorenko et al.'s conclusions about syntax-selectivity in the brain because of the multiple potential mappings between linguistic theory and neurobiology beyond individual brain regions.}, } @article {pmid40092333, year = {2025}, author = {Cihon, JH and Schlinger, HD and Ferguson, JL and Leaf, JB and Milne, CM}, title = {Is ACTraining Behavior Analytic? A Review of Tarbox et al. (2020).}, journal = {Behavior analysis in practice}, volume = {18}, number = {1}, pages = {29-33}, pmid = {40092333}, issn = {1998-1929}, abstract = {In an effort to determine if acceptance and commitment training (ACTraining) can be called behavior analytic, Tarbox et al. (2020) evaluated whether (1) ACTraining methods can be linked to behavior analytic principles, (2) they align with the seven dimensions of applied behavior analysis described by Baer et al. (1968, 1987), and (3) ACTraining relates to items on the Behavior Analyst Certification Board (BACB) task list. We briefly address, from a pragmatic, functional-analytic perspective, Tarbox et al.'s arguments and contend that they are not sufficient to conclude that ACTraining meets the conditions under which it would be considered behavior analytic. If this is the case, ACTraining would not fall under the scope of practice of Board Certified Behavior Analysts (BCBAs) and, moreover, may pose ethical problems for any BCBAs implementing ACTraining without a disclaimer that doing so is not covered by the BACB credential.}, } @article {pmid37885845, year = {2023}, author = {Himmelberger, ZM and Faught, GG and Tungate, AS and Conners, FA and Merrill, EC}, title = {Personality traits predict attitudes toward individuals with intellectual disability.}, journal = {International journal of developmental disabilities}, volume = {69}, number = {6}, pages = {906-914}, pmid = {37885845}, issn = {2047-3877}, abstract = {Background: Explaining individual differences in people's attitudes toward individuals with intellectual disability (ID) is important for increasing social inclusion of people with ID. The aim of the current study was to replicate and extend past research by formulating a single model of attitudes toward individuals with ID with several predictors: personality traits, quality and quantity of contact, perceived knowledge of ID, social desirability, and demographics. Methods: A sample of 221 undergraduate students in the United States completed several surveys in a lab setting: the Mental Retardation Attitude Inventory-Revised, the Big Five Inventory, McManus et al.'s measures of contact with and perceived knowledge of ID, and the Marlowe-Crowne Social Desirability Scale. Results: Results replicated previous findings by showing quality of contact was the strongest predictor of attitudes. Additionally, we found openness to experience and agreeableness remained significant predictors after holding all other variables constant. A follow-up mediation analysis demonstrated that quality of contact mediated the relations from openness and agreeableness to attitudes. Conclusions: Findings suggest personality factors can influence attitudes toward individuals with ID, and further emphasize the importance of quality of contact. Implications for the social inclusion of individuals with ID are discussed.}, } @article {pmid39238808, year = {2022}, author = {Meiling, JB and Barndt, BS and Ha, CT and Eubanks, JE and Schappell, JB and Raum, GM and Khan, SA and Prokop, L and Conger, A and McCormick, ZL and Hunt, CL}, title = {The therapeutic effect of genicular nerve radiofrequency for chronic knee pain after a total knee arthroplasty: A systematic review.}, journal = {Interventional pain medicine}, volume = {1}, number = {1}, pages = {100072}, pmid = {39238808}, issn = {2772-5944}, abstract = {OBJECTIVE: Summarize the therapeutic pain-reducing effects of GnRF for refractory post-TKA knee pain. A secondary objective was to summarize improvements in physical function after GnRF.

METHODS: A protocol was registered, and a database search conducted by an experienced librarian of all available studies in the English language up until November 3, 2021. Study inclusion criteria were randomized controlled trials (RCTs), prospective and retrospective longitudinal studies, cross-sectional studies, case series, case reports, studies involving adults ≥18 years of age, and studies written about the use of GnRF for the alleviation of chronic knee pain after receiving a TKA. The study quality and risk of bias was assessed using NHLBI Study Quality of Assessment Tools and Murad et al.'s Quality Assessment of Case Reports. Certainty in the evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation approach.

RESULTS: A total of 229 studies were screened, 11 met the inclusion criteria, and 265 patients underwent GnRF. Study designs included 1 double-blind pragmatic RCT, 5 retrospective cohort studies, 2 retrospective case series, and 3 case reports. The overall study quality assessment demonstrated three studies had "good", six "fair", and two "poor" quality. There have been positive responses to GnRF for post-TKA chronic knee pain in a range of 30-100% of patients.

CONCLUSIONS: According to GRADE, there is limited evidence, associated with low certainty to support the use of GnRF to ameliorate chronic knee pain after TKA, largely due to inconsistency and risk of bias. The studies included in this review reported positive results in pain and disability, and relatively few adverse events.}, } @article {pmid37520690, year = {2021}, author = {Lebrun, AM and Su, CJ and Bouchet, P}, title = {Domestic tourists' experience in protected natural parks: A new trend in pandemic crisis?.}, journal = {Journal of outdoor recreation and tourism}, volume = {35}, number = {}, pages = {100398}, pmid = {37520690}, issn = {2213-0799}, abstract = {Since December 2019, the Covid-19 pandemic crisis has led to profound changes around the world with a lot of interdictions or constraints to travel outside one's own country. One of the major consequences has been the development of proximity tourism in outdoor spaces less conducive to the spread of the virus. From a study preceding this pandemic, this article seeks to better understand the experiences lived by domestic tourists when they visited protected natural parks in their country. Beyond the health risks, it analyses the dimensions and the influences of experiences lived in these parks by French domestic tourists (n = 500) using Pine and Gilmore's 4Es model (1999). From a literature on the tourism experiences for domestic tourists adapted to natural parks and a critical review on the use and validation of Oh et al.'s scale (2007) in tourism, a structural equation model and a nested SEM show the positive relationship between three dimensions of the 4Es on the arousal and memory outcomes. Theoretically and methodologically speaking, this study extends the 4Es model in the direction of low arousal and mundane experiences for domestic tourists in protected natural parks, and questions Oh, Fiore, and Jeoung (2007) scale through the number of items, the use of EFA and the removal of the aesthetics dimension. This research can help managers of protected natural parks adapt their domestic tourists' experience offer during health crisis by implementing specific marketing strategies for low arousal and mundane experiences with more outdoor activities and digital services.}, } @article {pmid37052419, year = {2021}, author = {Fong, CJ and Taylor, J and Berdyyeva, A and McClelland, AM and Murphy, KM and Westbrook, JD}, title = {Interventions for improving employment outcomes for persons with autism spectrum disorders: A systematic review update.}, journal = {Campbell systematic reviews}, volume = {17}, number = {3}, pages = {e1185}, pmid = {37052419}, issn = {1891-1803}, abstract = {BACKGROUND: The incidence of autism spectrum disorders (ASD) is on the rise. Currently, 1 in 59 children are identified with ASD in the United States. ASD refers to a range of neurological disorders that involve some degree of difficulty with communication and interpersonal relationships. The range of the spectrum for autism disorders is wide with those at the higher functioning end often able to lead relatively independent lives and complete academic programs even while demonstrating social awkwardness. Those at the lower functioning end of the autism spectrum often demonstrate physical limitations, may lack speech, and have the inability to relate socially with others. As persons with ASD age, options such as employment become increasingly important as a consideration for long-term personal planning and quality of life. While many challenges exist for persons with ASD in obtaining and maintaining employment, some research shows that, with effective behavioral and social interventions, employment can occur. About 37% of individuals with ASD report having been employed for 12 months or more, 4 years after exiting high school. However, several studies show that individuals with ASD are more likely to lose their employment for behavioral and social interaction problems rather than their inability to perform assigned work tasks. Although Westbrook et al. (2012a, 2013, 2015) have reviewed the literature on interventions targeting employment for individuals with ASD, this review is outdated and does not account for recent developments in the field.

OBJECTIVES: The objective of this review is to determine the effectiveness of employment interventions in securing and maintaining employment for adults and transition-age youth with ASD, updating two reviews by Westbrook et al. (2012a, 2013).

SEARCH METHODS: The comprehensive search strategy used to identify relevant studies included a review of 28 relevant electronic databases. Search terminology for each of the electronic databases was developed from available database thesauri. Appropriate synonyms were used to maximize the database search output. Several international databases were included among the 28 databases searched. In addition, the authors identified and reviewed gray literature through analysis of reference lists of relevant studies. Unpublished dissertations and theses were also identified through database searches. The programs of conferences held by associations and organizations relevant to ASD and employment were also searched. In sum, the search strategy replicated and expanded the prior search methods used by Westbrook et al. (2012a, 2013).

SELECTION CRITERIA: Selection criteria consisted of an intervention evaluation using a randomized controlled trial or quasi-experimental design, an employment outcome, and a population of individuals with ASD.

DATA COLLECTION AND ANALYSIS: We updated the search from Westbrook et al., replicating and broadening the information retrieval processes. Our wide array of sources included electronic databases, gray literature, and conference and organization websites. Once all potentially relevant studies were located, pairs of coders evaluated the relevance of each title and abstract. Among the studies deemed potentially relevant, 278 were subjected to full-text retrieval and screening by pairs of coders. Because many intervention studies did not include employment outcomes, only three studies met our inclusion criteria. Given the small number of included studies, meta-analytic procedures were not used; rather, we opted to use more narrative and descriptive analysis to summarize the available evidence, including an assessment of risk of bias.

RESULTS: The systematic review update identified three studies that evaluated employment outcomes for interventions for individuals with ASD. All three studies identified in the review suggest that vocation-focused programs may have positive impacts on the employment outcomes for individuals with ASD. Wehman et al. indicated that participants in Project SEARCH had higher employment rates than control participants at both 9-month and 1-year follow-up time points. Adding autism spectrum disorder supports, Project SEARCH in Wehman et al.'s study also demonstrated higher employment rates for treatment participants than control participants at postgraduation, 3-month follow-up, and 12-month follow-up. Smith et al. found that virtual reality job interview training was able to increase the number of job offers treatment participants received compared to control participants.

AUTHORS' CONCLUSIONS: Given that prior reviews did not identify interventions with actual employment outcomes, the more recent emergence of evaluations of such programs is encouraging. This suggests that there is a growing body of evidence regarding interventions to enhance the employment outcomes for individuals with ASD but also greater need to conduct rigorous trials of vocation-based interventions for individuals with ASD that measure employment outcomes.}, } @article {pmid37089998, year = {2021}, author = {Pinto, RM and Park, SE and Miles, R and Ong, PN}, title = {Community engagement in dissemination and implementation models: A narrative review.}, journal = {Implementation research and practice}, volume = {2}, number = {}, pages = {2633489520985305}, pmid = {37089998}, issn = {2633-4895}, abstract = {BACKGROUND: Responding to the growing demand for scientific understanding of adoption and uptake of evidence-based interventions (EBIs), numerous dissemination and implementation ("D&I") models have been proposed in the extant literature. This review aimed to identify community-specific constructs with the potential to help researchers engage community partners in D&I studies or deploy EBIs.

METHODS: We identified 74 D&I models targeting community-level changes. We built on Tabak et al.'s narrative review that identified 51 D&I models published up to 2012 and identified 23 D&I models published between 2012 and 2020 from the Health Research & Practice website (16 models) and PubMed database (7 models). Three coders independently examined all 74 models looking for community-specific engagement constructs.

RESULTS: We identified five community engagement constructs: (1) Communication, (2) Partnership Exchange, (3) Community Capacity Building, (4) Leadership, and (5) Collaboration. Of the 74 models, 20% reflected all five constructs; 32%, four; 22%, three; 20%, two; and 5%, only one. Few models with strong community content have been introduced since 2009.

CONCLUSION: This article bridges the community-engaged and D&I research literature by identifying community engagement constructs reflected in existing D&I models, targeting community-level changes. Implications for future research and practice are discussed.

PLAIN LANGUAGE SUMMARY: Responding to the growing demand for scientific understanding of adoption and uptake of evidence-based interventions (EBIs), numerous dissemination and implementation ("D&I") models have been proposed. This review aimed to identify community-specific constructs with the potential to help researchers engage community partners in D&I studies or deploy EBIs. We identified 74 D&I models targeting community-level changes, published between 2012 and 2020. Three coders independently examined all 74 models looking for community-specific engagement constructs. We identified five community engagement constructs: (1) Communication, (2) Partnership Exchange, (3) Community Capacity Building, (4) Leadership, and (5) Collaboration. Of the 74 models, 20% reflected all five constructs; 32%, four; 22%, three; 20%, two; and 5%, only one. This article identified community engagement constructs reflected in existing D&I models targeting community-level changes. Implications for future research and practice are discussed.}, } @article {pmid38074596, year = {2018}, author = {Ledger, A and Joynes, V}, title = {"A huge part of my life": Exploring links between music, medical education, and students' developing identities as doctors.}, journal = {MedEdPublish (2016)}, volume = {7}, number = {}, pages = {183}, pmid = {38074596}, issn = {2312-7996}, abstract = {This article was migrated. The article was marked as recommended. This paper explores the place of music in the development of future doctors, through the lens of a mixed method, longitudinal evaluation of a two-week music and medicine special studies project for second and third year medical students. Methods of evaluation included a cohort-wide survey (n=147) and individual interviews with students who had undertaken the music and medicine project (n = 4). Analysis of survey responses indicated that music is important to medical students and that many students recognise links between music and medicine. Medical students who undertook the music and medicine project reported benefits for their ongoing development, including changes in the way they understand and use music in their own lives and exposure to career options they had not considered previously. These benefits are discussed in relation to Dennhardt et al.'s (2016) framework of epistemic functions of arts-based teaching in medical education and to wider debates about whether medical humanities teaching should be compulsory or optional. We then propose that there is room for music in medical education within integrated medical humanities teaching, to promote critical thinking and openness to new perspectives. Optional music and medicine study should also be available for medical students who identify as musicians, to support them in the process of developing their identities as doctors.}, } @article {pmid38406461, year = {2017}, author = {Ellaway, R and Topps, D}, title = {METRICS: a pattern language of scholarship in medical education.}, journal = {MedEdPublish (2016)}, volume = {6}, number = {}, pages = {199}, pmid = {38406461}, issn = {2312-7996}, abstract = {This article was migrated. The article was marked as recommended. Scholarly activity in health professions education has been growing steadily but despite the broad interest, quite what is considered to be scholarly activity in medical education has remained vague. Boyer's classes of scholarly activity (Boyer 1990) and Glassick et al.'s criteria required of an artefact to render it scholarly (Glassick et al. 1997) have been widely discussed. While the Glassick model has helped to define to what scholarly activity should be, we have found the Boyer model of what kinds of activity count as scholarship is lacking. We have developed the METRICS model of scholarly activity in medical education that maps more directly to scholarly activities. Metascholarship - activities that reflect on the nature of scholarshipEvaluation - activities that measure value or axiologyTranslation - activities that move findings or practices from one domain to anotherResearch - activities that focus on theory generation or testing (experimental, descriptive or explanatory)Innovation - activities that focus on creating new ideas, objects and practicesConceptual - activities that explore or develop new models, concepts, and paradigmsSynthesis - activities that focus on the integration of existing knowledge and practice Having built the METRICS model and tested it extensively in our own practice, we now seek to engage others in its use and appraisal.}, } @article {pmid37924192, year = {2015}, author = {Reed, LI and Deutchman, P and Schmidt, KL}, title = {Effects of Tearing on the Perception of Facial Expressions of Emotion.}, journal = {Evolutionary psychology : an international journal of evolutionary approaches to psychology and behavior}, volume = {13}, number = {4}, pages = {1474704915613915}, pmid = {37924192}, issn = {1474-7049}, abstract = {What is the function of emotional tearing? Previous work has found a tear effect, which resolves ambiguity in neutral expressions and increases perceptions of sadness in sad expressions. Tearing, however, is associated with a variety of emotional states, and it remains unclear how the tear effect generalizes to other emotion expressions. Here we expand upon previous works by examining ratings of video clips depicting posed facial expressions presented with and without tears. We replicate Provine et al.'s (2009) findings that tearing increases perceptions of sadness in sad expressions. Furthermore, we find that tearing has specific effects on ratings of emotion (happiness, sadness, anger, and fear) and ratings of intensity and valence in neutral, positive, and negative expressions. These results suggest that tearing may serve a specific and independent communicative function, interacting with those of various expressions.}, } @article {pmid36864740, year = {2023}, author = {Xiao, LY}, title = {Debate: Academics should collaborate with the technology industry, but not in lieu of noncollaborative research.}, journal = {Child and adolescent mental health}, volume = {28}, number = {2}, pages = {338-340}, doi = {10.1111/camh.12644}, pmid = {36864740}, issn = {1475-357X}, mesh = {Child ; Humans ; Adolescent ; *Industry ; *Technology ; }, abstract = {Academic research collaborations with the technology industry should be complementary to and, importantly, must not replace noncollaborative research that is independent from the industry (and, in particular, 'adversarial research' whose negative findings will likely operate against industry interests). Reflecting on the author's own research projects concerning companies' compliance with video game loot box regulation, he agrees with Livingstone et al.'s proposition (Child and Adolescent Mental Health, 2022, 28, 150) that research seeking to identify problems (and thereby work against the industry's interests) should be conducted independently (p. 151), at least initially. He also echoes the sentiment expressed by Zendle and Wardle (Child and Adolescent Mental Health, 2022, 28, 155) that 'a moratorium' (p. 156) or a ban on industry collaborations is not a proportional response to legitimate concerns about conflict of interest stemming from the video game industry's discretionary provision of data access. A combined approach that conducts both noncollaborative and collaborative research, but with the latter being conducted only after the former's unbiased results are known, might prove fruitful. Academics must bear in mind that industry involvement at any particular stage of the research, or at all, is not always appropriate. Some research questions should not and cannot be answered objectively with industry involvement. Funding bodies and other stakeholders should also recognise this and not render industry collaboration compulsory.}, } @article {pmid36855220, year = {2023}, author = {Albright, C and Limoges, J and Rempel, GR}, title = {Living with pulmonary sequelae of COVID-19 and the implications for clinical nursing practice: A qualitative systematised review.}, journal = {Journal of clinical nursing}, volume = {32}, number = {21-22}, pages = {7650-7660}, doi = {10.1111/jocn.16664}, pmid = {36855220}, issn = {1365-2702}, mesh = {Adult ; Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19/epidemiology ; Qualitative Research ; *Nursing Care ; Clinical Competence ; }, abstract = {AIM: To synthesise qualitative research on pulmonary sequelae of COVID-19 and identify patient needs and experiences to develop nursing care strategies.

BACKGROUND: Qualitative research on long COVID by subtype has not yet occurred. As pulmonary sequelae constitute a serious long COVID subtype, exploring patient experience and needs can generate knowledge to guide nursing practice.

DESIGN: Systematised review methodology utilised on a purposive sample of published articles and reported using the PRISMA guidelines and checklists. Searched MEDLINE, Cumulative Index to Nursing and Allied Health, and Google Scholar, for English or French articles published from February 2020 to June 2022; qualitative research with adults recovering from COVID-19 with evidence of pulmonary sequelae.

METHODS: Established principles for data extraction followed related to data reduction, data presentation, data comparison, and conclusion formulation and verification. Analysis was informed by Thorne's Interpretive Description and extended with Meleis' transitions theory, Mishel's uncertainty in illness theory and Moore et al.'s holistic theory of unpleasant symptoms. The quality of included studies was assessed Joanna Briggs Institute critical appraisal tool for qualitative research.

RESULTS: Four articles with six pooled participants provided data to yield three main themes: (1) a novel health-illness transition, (2) lung injury and pulmonary fibrosis as antecedent to illness uncertainty, (3) and pulmonary symptoms that are compounded by fatigue and weakness.

CONCLUSION: Pulmonary sequelae of COVID-19 confers a unique health-illness transition, uncertainties and symptoms that can be addressed by theory informed nursing practice.

Advocacy, optimising the nurse-patient relationship, offering up-to-date information and addressing uncertainty may help patients cope with pulmonary sequelae, a complex subtype of long COVID with important considerations for clinical nursing care. Despite a lack of evidence-informed clinical pathways, nurses can support patients to understand novel treatments, support discharge planning and acknowledge the synergistic nature of pulmonary symptoms and fatigue to support health-illness transitions.

This article involved analysis of previously published works.}, } @article {pmid36850634, year = {2023}, author = {Park, Y and Ryu, D and Kwon, D and Park, Y}, title = {Provably Secure Mutual Authentication and Key Agreement Scheme Using PUF in Internet of Drones Deployments.}, journal = {Sensors (Basel, Switzerland)}, volume = {23}, number = {4}, pages = {}, pmid = {36850634}, issn = {1424-8220}, support = {2019//Keimyung University/ ; }, abstract = {Internet of Drones (IoD), designed to coordinate the access of unmanned aerial vehicles (UAVs), is a specific application of the Internet of Things (IoT). Drones are used to control airspace and offer services such as rescue, traffic surveillance, environmental monitoring, delivery and so on. However, IoD continues to suffer from privacy and security issues. Firstly, messages are transmitted over public channels in IoD environments, which compromises data security. Further, sensitive data can also be extracted from stolen mobile devices of remote users. Moreover, drones are susceptible to physical capture and manipulation by adversaries, which are called drone capture attacks. Thus, the development of a secure and lightweight authentication scheme is essential to overcoming these security vulnerabilities, even on resource-constrained drones. In 2021, Akram et al. proposed a secure and lightweight user-drone authentication scheme for drone networks. However, we discovered that Akram et al.'s scheme is susceptible to user and drone impersonation, verification table leakage, and denial of service (DoS) attacks. Furthermore, their scheme cannot provide perfect forward secrecy. To overcome the aforementioned security vulnerabilities, we propose a secure mutual authentication and key agreement scheme between user and drone pairs. The proposed scheme utilizes physical unclonable function (PUF) to give drones uniqueness and resistance against drone stolen attacks. Moreover, the proposed scheme uses a fuzzy extractor to utilize the biometrics of users as secret parameters. We analyze the security of the proposed scheme using informal security analysis, Burrows-Abadi-Needham (BAN) logic, a Real-or-Random (RoR) model, and Automated Verification of Internet Security Protocols and Applications (AVISPA) simulation. We also compared the security features and performance of the proposed scheme and the existing related schemes. Therefore, we demonstrate that the proposed scheme is suitable for IoD environments that can provide users with secure and convenient wireless communications.}, } @article {pmid36849054, year = {2023}, author = {Foxon, F}, title = {Re: "Impact of the e-cigarette era on cigarette smoking among youth in the United States: A population-level study".}, journal = {Preventive medicine}, volume = {169}, number = {}, pages = {107444}, doi = {10.1016/j.ypmed.2023.107444}, pmid = {36849054}, issn = {1096-0260}, mesh = {Humans ; Adolescent ; United States/epidemiology ; *Cigarette Smoking/epidemiology ; *Electronic Nicotine Delivery Systems ; }, abstract = {This is a letter to the editor of Preventive Medicine responding to Harrell et al.'s "Impact of the e-cigarette era on cigarette smoking among youth in the United States: A population-level study." (Harrell MB, Mantey DS, Baojiang C, Kelder SH, Barrington-Trimis J. Impact of the e-cigarette era on cigarette smoking among youth in the United States: A population-level study. Preventive Medicine 2022;164:107265).}, } @article {pmid36847558, year = {2023}, author = {Kiel, EJ}, title = {The developmental psychopathology of detection and dual control - a commentary on Fox et al. (2023).}, journal = {Journal of child psychology and psychiatry, and allied disciplines}, volume = {64}, number = {4}, pages = {562-565}, doi = {10.1111/jcpp.13771}, pmid = {36847558}, issn = {1469-7610}, support = {R01 MH113669/MH/NIMH NIH HHS/United States ; }, mesh = {Humans ; *Psychopathology ; Anxiety Disorders ; Mental Health ; *Mental Disorders ; }, abstract = {Behavioral inhibition in early life is among the robust predictors of later anxiety problems, particularly social anxiety, one of the most pressing mental health concerns across the lifespan. However, the predictive relation is far from perfect. Fox et al. reviewed the literature and their Detection and Dual Control framework to emphasize the role of moderators in the etiology of social anxiety. In doing so, they exemplify a developmental psychopathology approach. This commentary aligns the core features of Fox et al.'s review and theoretical model with specific tenets of developmental psychopathology. These tenets provide a structure for integrating the Detection and Dual Control framework with other developmental psychopathology models and guiding future directions for the field.}, } @article {pmid36841319, year = {2023}, author = {Castelijns, MC and Hageman, SHJ and Teraa, M and van der Meer, MG and Westerink, J and Costa, F and Ten Berg, JM and Visseren, FLJ and , }, title = {External validation of bleeding risk models for the prediction of long-term bleeding risk in patients with established cardiovascular disease.}, journal = {American heart journal}, volume = {260}, number = {}, pages = {72-81}, doi = {10.1016/j.ahj.2023.02.011}, pmid = {36841319}, issn = {1097-6744}, mesh = {Humans ; *Cardiovascular Diseases/etiology/chemically induced ; Platelet Aggregation Inhibitors/adverse effects ; Risk Assessment ; Hemorrhage/etiology/chemically induced ; *Percutaneous Coronary Intervention/adverse effects ; Risk Factors ; }, abstract = {OBJECTIVE: The long-term predictive performance of existing bleeding risk models in patients with various manifestations of cardiovascular disease (CVD) is not well known. This study aims to assess and compare the performance of relevant existing bleeding risk models in estimating the long-term risk of major bleeding in a cohort of patients with established CVD.

METHODS: Seven existing bleeding risk models (PRECISE-DAPT, DAPT, Ducrocq et al, de Vries et al, S2TOP-BLEED, Intracranial B2LEED3S and HAS-BLED) were identified and externally validated in 7,249 patients with established CVD included in the Utrecht Cardiovascular Cohort-second manifestations of arterial disease study. Predictive performance was assessed in terms of discrimination and calibration, both at 10 years and the original prediction horizon of the models. Major bleeding was defined as Bleeding Academic Research Consortium type 3 or 5.

RESULTS: After a median follow-up of 8.4 years (interquartile range 4.5-12.5), a total of 233 (3.2%) major bleeding events occurred. C-statistics for discrimination at 10 years ranged from 0.53 (95%CI 0.49-0.57) to 0.64 (95%CI 0.60-0.68). Calibration plots after recalibration to 10 years showed best agreement between predicted and observed bleeding risk for De Vries et al, S2TOP-BLEED, DAPT and PRECISE-DAPT.

CONCLUSIONS: The performance of existing bleeding risk models to predict long-term bleeding in patients with CVD varied. Discrimination and calibration were best for the models of de Vries et al, S2TOP-BLEED, DAPT and PRECISE-DAPT. Of these, recalibrated models requiring the least predictors may be preferred for use to personalize prevention with antithrombotic therapy.}, } @article {pmid36832372, year = {2023}, author = {Aguayo-Estremera, R and Cañadas, GR and Albendín-García, L and Ortega-Campos, E and Ariza, T and Monsalve-Reyes, CS and De la Fuente-Solana, EI}, title = {Prevalence of Burnout Syndrome and Fear of COVID-19 among Adolescent University Students.}, journal = {Children (Basel, Switzerland)}, volume = {10}, number = {2}, pages = {}, pmid = {36832372}, issn = {2227-9067}, support = {P20_00627//Regional Government of Andalusia/ ; }, abstract = {This study aimed to estimate the prevalence of burnout syndrome in adolescents entering university studies, to detect differences in burnout levels, personality factors and fear of coronavirus in a pandemic context due to COVID-19. A cross-sectional predictive study was performed with a sample that comprised 134 individuals in their first year of a Psychology degree at Spanish universities. The Maslach Burnout Inventory Student Survey, the NEO Five-Factor Inventory and the Fear of COVID-19 Scale were applied. The prevalence of burnout is estimated according to three methods: Maslach and Jackson's severity classification, Golembiewski's phase model and Maslach et al.'s profile model. The estimates show significant differences. The results indicated that between 9 and 21% of students were at risk of developing burnout. On the other hand, students who reported having suffered psychological consequences of the pandemic showed greater emotional exhaustion, neuroticism and fear of COVID-19, and a lower level of personal accomplishment than those who did not suffer such consequences. Neuroticism was the only significant predictor for all burnout dimensions, and fear of COVID-19 did not contribute to any of them.}, } @article {pmid36830535, year = {2023}, author = {Wolframm, IA and Douglas, J and Pearson, G}, title = {Changing Hearts and Minds in the Equestrian World One Behaviour at a Time.}, journal = {Animals : an open access journal from MDPI}, volume = {13}, number = {4}, pages = {}, pmid = {36830535}, issn = {2076-2615}, abstract = {Equestrianism is currently facing a range of pressing challenges. These challenges, which are largely based on evolving attitudes to ethics and equine wellbeing, have consequences for the sport's social licence to operate. The factors that may have contributed to the current situation include overarching societal trends, specific aspects of the equestrian sector, and factors rooted in human nature. If equestrianism is to flourish, it is evident that much needs to change, not the least, human behaviour. To this end, using established behaviour change frameworks that have been scientifically validated and are rooted in practice-most notably, Michie et al.'s COM-B model and Behaviour Change Wheel-could be of practical value for developing and implementing equine welfare strategies. This review summarises the theoretical underpinnings of some behaviour change frameworks and provides a practical, step-by-step approach to designing an effective behaviour change intervention. A real-world example is provided through the retrospective analysis of an intervention strategy that aimed to increase the use of learning theory in (educational) veterinary practice. We contend that the incorporation of effective behaviour change interventions into any equine welfare improvement strategy may help to safeguard the future of equestrianism.}, } @article {pmid36821633, year = {2023}, author = {Mitchell, RE and Hartley, AE and Walker, VM and Gkatzionis, A and Yarmolinsky, J and Bell, JA and Chong, AHW and Paternoster, L and Tilling, K and Smith, GD}, title = {Strategies to investigate and mitigate collider bias in genetic and Mendelian randomisation studies of disease progression.}, journal = {PLoS genetics}, volume = {19}, number = {2}, pages = {e1010596}, pmid = {36821633}, issn = {1553-7404}, support = {MC_UU_00011/3/MRC_/Medical Research Council/United Kingdom ; MC_UU_00019/4/MRC_/Medical Research Council/United Kingdom ; MC_UU_00011/1/MRC_/Medical Research Council/United Kingdom ; MC_PC_20059/MRC_/Medical Research Council/United Kingdom ; MC_UU_00032/1/MRC_/Medical Research Council/United Kingdom ; MC_UU_00011/4/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Humans ; *Genome-Wide Association Study ; Bias ; Risk Factors ; Phenotype ; *Mendelian Randomization Analysis/methods ; Disease Progression ; }, abstract = {Genetic studies of disease progression can be used to identify factors that may influence survival or prognosis, which may differ from factors that influence on disease susceptibility. Studies of disease progression feed directly into therapeutics for disease, whereas studies of incidence inform prevention strategies. However, studies of disease progression are known to be affected by collider (also known as "index event") bias since the disease progression phenotype can only be observed for individuals who have the disease. This applies equally to observational and genetic studies, including genome-wide association studies and Mendelian randomisation (MR) analyses. In this paper, our aim is to review several statistical methods that can be used to detect and adjust for index event bias in studies of disease progression, and how they apply to genetic and MR studies using both individual- and summary-level data. Methods to detect the presence of index event bias include the use of negative controls, a comparison of associations between risk factors for incidence in individuals with and without the disease, and an inspection of Miami plots. Methods to adjust for the bias include inverse probability weighting (with individual-level data), or Slope-Hunter and Dudbridge et al.'s index event bias adjustment (when only summary-level data are available). We also outline two approaches for sensitivity analysis. We then illustrate how three methods to minimise bias can be used in practice with two applied examples. Our first example investigates the effects of blood lipid traits on mortality from coronary heart disease, while our second example investigates genetic associations with breast cancer mortality.}, } @article {pmid36821554, year = {2023}, author = {Saatchi, AG and Pallotti, F and Sullivan, P}, title = {Network approaches and interventions in healthcare settings: A systematic scoping review.}, journal = {PloS one}, volume = {18}, number = {2}, pages = {e0282050}, pmid = {36821554}, issn = {1932-6203}, mesh = {Humans ; *Health Personnel ; Hospitals ; Delivery of Health Care ; *Physicians ; Social Networking ; }, abstract = {INTRODUCTION: The growing interest in networks of interactions is sustained by the conviction that they can be leveraged to improve the quality and efficiency of healthcare delivery systems. Evidence in support of this conviction, however, is mostly based on descriptive studies. Systematic evaluation of the outcomes of network interventions in healthcare settings is still wanting. Despite the proliferation of studies based on Social Network Analysis (SNA) tools and techniques, we still know little about how intervention programs aimed at altering existing patterns of social interaction among healthcare providers affect the quality of service delivery. We update and extend prior reviews by providing a comprehensive assessment of available evidence.

METHODS AND FINDINGS: We searched eight databases to identify papers using SNA in healthcare settings published between 1st January 2010 and 1st May 2022. We followed Chambers et al.'s (2012) approach, using a Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) checklist. We distinguished between studies relying on SNA as part of an intervention program, and studies using SNA for descriptive purposes only. We further distinguished studies recommending a possible SNA-based intervention. We restricted our focus on SNA performed on networks among healthcare professionals (e.g., doctors, nurses, etc.) in any healthcare setting (e.g., hospitals, primary care, etc.). Our final review included 102 papers. The majority of the papers used SNA for descriptive purposes only. Only four studies adopted SNA as an intervention tool, and measured outcome variables.

CONCLUSIONS: We found little evidence for SNA-based intervention programs in healthcare settings. We discuss the reasons and challenges, and identify the main component elements of a network intervention plan. Future research should seek to evaluate the long-term role of SNA in changing practices, policies and behaviors, and provide evidence of how these changes affect patients and the quality of service delivery.}, } @article {pmid36814275, year = {2023}, author = {Wyatt, TR and Wood, EA and Waller, JL and Egan, SC and Stepleman, LM}, title = {Patient care ownership in medical students: a validation study.}, journal = {BMC medical education}, volume = {23}, number = {1}, pages = {127}, pmid = {36814275}, issn = {1472-6920}, mesh = {Humans ; *Students, Medical/psychology ; Ownership ; Reproducibility of Results ; Burnout, Psychological ; Patient Care ; *Burnout, Professional ; Surveys and Questionnaires ; Factor Analysis, Statistical ; Psychometrics ; }, abstract = {BACKGROUND: Psychological Ownership is the cognitive-affective state individuals experience when they come to feel they own something. The construct is context-dependent reliant on what is being owned and by whom. In medical education, this feeling translates to what has been described as "Patient Care Ownership," which includes the feelings of responsibility that physicians have for patient care. In this study, we adapted an instrument on Psychological Ownership that was originally developed for business employees for a medical student population. The aim of this study was to collect validity evidence for its fit with this population.

METHODS: A revised version of the Psychological Ownership survey was created and administered to 182 medical students rotating on their clerkships in 2018-2019, along with two other measures, the Teamwork Assessment Scale (TSA) and Maslach Burnout Inventory (MBI) Survey. A confirmatory factor analysis (CFA) was conducted, which indicated a poor fit between the original and revised version. As a result, an exploratory factor analysis (EFA) was conducted and validity evidence was gathered to assess the new instruments' fit with medical students.

RESULTS: The results show that the initial subscales proposed by Avey et al. (i.e. Territoriality, Accountability, Belongingness, Self-efficacy, and Self-identification) did not account for item responses in the revised instrument when administered to medical students. Instead, four subscales (Team Inclusion, Accountability, Territoriality, and Self-Confidence) better described patient care ownership for medical students, and the internal reliability of these subscales was found to be good. Using Cronbach's alpha, the internal consistency among items for each subscale, includes: Team Inclusion (0.91), Accountability (0.78), Territoriality (0.78), and Self-Confidence (0.82). The subscales of Territoriality, Team Inclusion, and Self-Confidence were negatively correlated with the 1-item Burnout measure (P = 0.01). The Team Inclusion subscale strongly correlated with the Teamwork Assessment Scale (TSA), while the subscales of Accountability correlated weakly, and Self-Confidence and Territoriality correlated moderately.

CONCLUSION: Our study provides preliminary validity evidence for an adapted version of Avey et al.'s Psychological Ownership survey, specifically designed to measure patient care ownership in a medical student population. We expect this revised instrument to be a valuable tool to medical educators evaluating and monitoring students as they learn how to engage in patient care ownership.}, } @article {pmid36810744, year = {2023}, author = {Salomons, H and Smith, KCM and Callahan-Beckel, M and Callahan, M and Levy, K and Kennedy, BS and Bray, EE and Gnanadesikan, GE and Horschler, DJ and Gruen, M and Tan, J and White, P and vonHoldt, BM and MacLean, EL and Hare, B}, title = {Response to Hansen Wheat et al.: Additional analysis further supports the early emergence of cooperative communication in dogs compared to wolves raised with more human exposure.}, journal = {Learning & behavior}, volume = {51}, number = {2}, pages = {131-134}, pmid = {36810744}, issn = {1543-4508}, support = {R01 HD097732/HD/NICHD NIH HHS/United States ; }, mesh = {Dogs ; Animals ; Humans ; *Wolves/physiology ; Triticum ; Domestication ; Gestures ; }, abstract = {Here, we address Hansen Wheat et al.'s commentary in this journal in response to Salomons et al. Current Biology, 31(14), 3137-3144.E11, (2021). We conduct additional analyses in response to Hansen Wheat et al.'s two main questions. First, we examine the claim that it was the move to a human home environment which enabled the dog puppies to outperform the wolf puppies in gesture comprehension tasks. We show that the youngest dog puppies who had not yet been individually placed in raisers' homes were still highly skilled, and outperformed similar-aged wolf puppies who had higher levels of human interaction. Second, we address the claim that willingness to approach a stranger can explain the difference between dog and wolf pups' ability to succeed in gesture comprehension tasks. We explain the various controls in the original study that render this explanation insufficient, and demonstrate via model comparison that the covariance of species and temperament also make this parsing impossible. Overall, our additional analyses and considerations support the domestication hypothesis as laid out by Salomons et al. Current Biology, 31(14), 3137-3144.E11, (2021).}, } @article {pmid36810106, year = {2023}, author = {Stadnick, NA and Viglione, C and Crable, EL and Montoya, JL and Gholami, M and Su, I and Rabin, B}, title = {Enhancing review criteria for dissemination and implementation science grants.}, journal = {Implementation science communications}, volume = {4}, number = {1}, pages = {17}, pmid = {36810106}, issn = {2662-2211}, support = {K01 DA056838/DA/NIDA NIH HHS/United States ; K23 DA051324/DA/NIDA NIH HHS/United States ; UL1 TR001442/TR/NCATS NIH HHS/United States ; UL1 TR001442/GF/NIH HHS/United States ; }, abstract = {BACKGROUND: The existing grant review criteria do not consider unique methods and priorities of Dissemination and Implementation Science (DIS). The ImplemeNtation and Improvement Science Proposals Evaluation CriTeria (INSPECT) scoring system includes 10 criteria based on Proctor et al.'s "ten key ingredients" and was developed to support the assessment of DIS research proposals. We describe how we adapted INSPECT and used it in combination with the NIH scoring system to evaluate pilot DIS study proposals through our DIS Center.

METHODS: We adapted INSPECT to broaden considerations for diverse DIS settings and concepts (e.g., explicitly including dissemination and implementation methods). Five PhD-level researchers with intermediate to advanced DIS knowledge were trained to conduct reviews of seven grant applications using both the INSPECT and NIH criteria. The INSPECT overall scores range from 0 to 30 (higher scores are better), and the NIH overall scores range from 1 to 9 (lower scores are better). Each grant was independently reviewed by two reviewers, then discussed in a group meeting to compare the experiences using both criteria to evaluate the proposal and to finalize scoring decisions. A follow-up survey was sent to grant reviewers to solicit further reflections on each scoring criterion.

RESULTS: Averaged across reviewers, the INSPECT overall scores ranged from 13 to 24, while the NIH overall scores ranged from 2 to 5. Reviewer reflections highlighted the unique value and utility for each scoring criterion. The NIH criteria had a broad scientific purview and were better suited to evaluate more effectiveness-focused and pre-implementation proposals not testing implementation strategies. The INSPECT criteria were easier to rate in terms of the quality of integrating DIS considerations into the proposal and to assess the potential for generalizability, real-world feasibility, and impact. Overall, reviewers noted that INSPECT was a helpful tool to guide DIS research proposal writing.

CONCLUSIONS: We confirmed complementarity in using both scoring criteria in our pilot study grant proposal review and highlighted the utility of INSPECT as a potential DIS resource for training and capacity building. Possible refinements to INSPECT include more explicit reviewer guidance on assessing pre-implementation proposals, providing reviewers with the opportunity to submit written commentary with each numerical rating, and greater clarity on rating criteria with overlapping descriptions.}, } @article {pmid36808758, year = {2023}, author = {Røysland, IØ}, title = {Moving from one state to another among patients experiencing unexplained chest pain during physical activity: A secondary qualitative analysis by Meleis transition theory.}, journal = {Scandinavian journal of caring sciences}, volume = {37}, number = {3}, pages = {851-861}, doi = {10.1111/scs.13153}, pmid = {36808758}, issn = {1471-6712}, mesh = {Humans ; *Exercise ; *Chest Pain ; Health Status ; Qualitative Research ; }, abstract = {BACKGROUND: Unexplained chest pain is a common condition in medical settings. Nurses usually coordinate the rehabilitation of patients. Physical activity is recommended; however, it is one of the major avoidance behaviours in patients with coronary heart disease. There is a need for a deeper understanding of the transition that patients with unexplained chest pain undergo during physical activity.

AIM: To develop deeper understanding about experiences of transition in patients with unexplained chest pain during physical activity.

DESIGN: Secondary qualitative analysis of data from three exploratory studies.

METHOD: Meleis et al.'s transition theory was used as a framework for the secondary analysis.

FINDINGS: The transition was complex and multidimensional. The participants experienced personal processes of change toward health within the illness, corresponding to indicators of healthy transitions.

CONCLUSION: The process can be identified as a transition from an uncertain and often sick role to a healthy role. Knowledge regarding transition promotes a person-centred approach in which patients' perspectives are included. Nurses and other health professionals can better direct and plan the caring and rehabilitation of patients with unexplained chest pain by deepening their knowledge of the transition process based on physical activity.}, } @article {pmid36807223, year = {2023}, author = {Scheidegger, A and Goméz Penedo, JM and Blättler, LT and Aybek, S and Bischoff, N and Grosse Holtforth, M}, title = {Motive Satisfaction Among Patients with Chronic Primary Pain: A Replication.}, journal = {Journal of clinical psychology in medical settings}, volume = {30}, number = {4}, pages = {893-908}, pmid = {36807223}, issn = {1573-3572}, mesh = {Humans ; *Patient Satisfaction ; Motivation ; *Chronic Pain/therapy ; Surveys and Questionnaires ; Personal Satisfaction ; }, abstract = {We set out to replicate findings of significant (a) reductions in pain, psychological distress, and motivational incongruence (i.e., insufficient motive satisfaction) after interdisciplinary multimodal pain treatment and (b) associations between reductions in motivational incongruence (i.e., improved motive satisfaction) and decreases in psychological distress (Vincent et al., Journal of Clinical Psychology in Medical Settings 28:331-343, 2021). 475 Patients with chronic primary pain completed standardized self-reported questionnaires assessing motivational incongruence, psychological distress, pain intensity, and pain interference at intake and discharge from a tertiary psychosomatic university clinic. We used hierarchical linear models to analyze motivational incongruence's effects on psychological distress. We partially replicated Vincent et al.'s findings. Significant reductions in pain, psychological distress, and motivational incongruence after treatment were found. Reductions in motivational incongruence were associated with reductions in psychological distress. Similarly, a better motive satisfaction mediated the relationship between pain interference and psychological distress. Our findings show that reducing motivational incongruence may be a key component of treating chronic primary pain; we recommend to assess and target motivational incongruence to improve interdisciplinary multimodal pain treatment.}, } @article {pmid36805731, year = {2023}, author = {Carl, J and Barratt, J and Arbour-Nicitopoulos, KP and Barnett, LM and Dudley, DA and Holler, P and Keegan, R and Kwan, M and Scurati, R and Sum, RK and Wainwright, N and Cairney, J}, title = {Development, explanation, and presentation of the Physical Literacy Interventions Reporting Template (PLIRT).}, journal = {The international journal of behavioral nutrition and physical activity}, volume = {20}, number = {1}, pages = {21}, pmid = {36805731}, issn = {1479-5868}, mesh = {Humans ; *Literacy ; Consensus ; *Exercise ; Physical Education and Training ; Qualitative Research ; }, abstract = {BACKGROUND: The physical literacy (PL) concept integrates different personal (e.g., physical, cognitive, psychological/affective, social) determinants of physical activity and has received growing attention recently. Although practical efforts increasingly adopt PL as a guiding concept, latest evidence has shown that PL interventions often lack specification of important theoretical foundations and basic delivery information. Therefore, the goal of the present study was to develop an expert-based template that supports researchers and practitioners in planning and reporting PL interventions.

METHODS: The development process was informed by Moher et al.'s guidance for the development of research reporting guidelines. We composed a group of ten distinguished experts on PL. In two face-to-face meetings, the group first discussed a literature-driven draft of reporting items. In the second stage, the experts anonymously voted and commented on the items in two rounds (each leading to revisions) until consensus was reached.

RESULTS: The panel recommended that stakeholders of PL initiatives should tightly interlock interventional aspects with PL theory while ensuring consistency throughout all stages of intervention development. The Physical Literacy Interventions Reporting Template (PLIRT) encompasses a total of 14 items (two additional items for mixed-methods studies) in six different sections: title (one item), background and definition (three items), assessment (one item each for quantitative and qualitative studies), design and content (five items), evaluation (one item plus one item each for quantitative and qualitative studies), discussion and conclusion (two items).

CONCLUSION: The PLIRT was designed to facilitate improved transparency and interpretability in reports on PL interventions. The template has the potential to close gaps between theory and practice, thereby contributing to more holistic interventions for the fields of physical education, sport, and health.}, } @article {pmid36802696, year = {2023}, author = {Fosse, A and Abelsen, B and Svensson, A and Konradsen, I}, title = {Tension between local, regional and national level in Norwegian handling of COVID-19.}, journal = {Rural and remote health}, volume = {23}, number = {1}, pages = {8124}, doi = {10.22605/RRH8124}, pmid = {36802696}, issn = {1445-6354}, mesh = {Humans ; *COVID-19 ; Pandemics/prevention & control ; Infection Control ; Norway/epidemiology ; }, abstract = {INTRODUCTION: The initial phase of the COVID-19 pandemic can be described as a crisis - a threat that must be urgently addressed under conditions of deep uncertainty. We wanted to explore the tension between local, regional and national authorities evoked by some rural municipalities' decisions to impose local infection control measures during the first weeks of the COVID-19 pandemic in Norway.

METHODS: Eight municipal chief medical officers of health (CMO) and six crisis management teams participated in semi-structured and focus group interviews. Data were analyzed with systematic text condensation. Boin and Bynander's interpretation of crisis management and coordination and Nesheim et al.'s framework for non-hierarchical coordination in the state sector inspired the analysis.

RESULTS: Uncertainty in the face of a pandemic with unknown damage potential, lack of infection control equipment, patient transport challenges, vulnerable staff situation and planning of local COVID-19 beds were some of the reasons for rural municipalities imposing local infection control measures. Local CMOs' engagement, visibility and knowledge contributed to trust and safety. Differences in perspectives between local, regional and national actors created tension. Existing roles and structures were adjusted, and new informal networks arose.

DISCUSSION: Strong municipal responsibility in Norway and the quite unique arrangement with local CMOs in every municipality with legal right to decide temporary local infection control measures seemed to facilitate a fruitful balance between top-down and bottom-up decision-making. The following dialogue and mutual adjustment of perspectives led to appropriate balance between national and local measures in Norway's handling of the COVID-19 pandemic.}, } @article {pmid36800559, year = {2023}, author = {Kaya, P and İnanç Tekin, M and Özdal, PÇ}, title = {Authors Reply to Letter to the Editor - In Response to Comment on Raul E. Ruiz-Lozano et al.'s "Predictive Factors for the Prognosis of Vogt-Koyanagi-Harada Disease".}, journal = {Ocular immunology and inflammation}, volume = {31}, number = {8}, pages = {1738-1739}, doi = {10.1080/09273948.2023.2178940}, pmid = {36800559}, issn = {1744-5078}, mesh = {Humans ; *Uveomeningoencephalitic Syndrome/diagnosis/drug therapy ; Prognosis ; }, abstract = {An aggressive treatment, including immunomodulatory therapy, is very important in preventing the development of the chronic recurrent stage in Vogt-Koyanagı-Harada (VKH) disease. However, the way of treatment is not the only factor determining the prognosis, and there are other factors that affect the outcome.}, } @article {pmid36789471, year = {2023}, author = {Wertz, J and Lewis, SJ}, title = {Something old, something new - can adding genomic data to family studies advance our understanding of the impact of nature and nurture on mental health? Commentary on McAdams et al. (2023).}, journal = {Journal of child psychology and psychiatry, and allied disciplines}, volume = {64}, number = {4}, pages = {708-710}, doi = {10.1111/jcpp.13762}, pmid = {36789471}, issn = {1469-7610}, mesh = {Humans ; *Mental Health ; *Psychopathology ; Genomics ; }, abstract = {In their annual research review, McAdams, Cheesman, and Ahmadzadeh (2023) provide a thorough overview of how the use of novel genetically informative approaches can increase our knowledge about the intergenerational transmission of psychopathology. Many JCPP readers will already be familiar with genetically sensitive family-based designs, such as twin and adoption studies, as well as with newer molecular-genetic approaches, such as polygenic-score studies. McAdams et al.'s (2023) review discusses the innovative combination of family-based and molecular-genetic methods, and what this combination can reveal about developmental psychopathology.}, } @article {pmid36781117, year = {2023}, author = {Del Giudice, M}, title = {Arbitrary, inappropriate grading criteria distort the evaluation of evidence: A comment on Kim et al.'s (2022) umbrella review.}, journal = {Neuroscience and biobehavioral reviews}, volume = {147}, number = {}, pages = {105089}, doi = {10.1016/j.neubiorev.2023.105089}, pmid = {36781117}, issn = {1873-7528}, } @article {pmid36780217, year = {2023}, author = {Riquelme, JL and Hemberger, M and Laurent, G and Gjorgjieva, J}, title = {Single spikes drive sequential propagation and routing of activity in a cortical network.}, journal = {eLife}, volume = {12}, number = {}, pages = {}, pmid = {36780217}, issn = {2050-084X}, mesh = {Reproducibility of Results ; *Neurons/physiology ; *Models, Neurological ; Synapses/physiology ; Action Potentials/physiology ; }, abstract = {Single spikes can trigger repeatable firing sequences in cortical networks. The mechanisms that support reliable propagation of activity from such small events and their functional consequences remain unclear. By constraining a recurrent network model with experimental statistics from turtle cortex, we generate reliable and temporally precise sequences from single spike triggers. We find that rare strong connections support sequence propagation, while dense weak connections modulate propagation reliability. We identify sections of sequences corresponding to divergent branches of strongly connected neurons which can be selectively gated. Applying external inputs to specific neurons in the sparse backbone of strong connections can effectively control propagation and route activity within the network. Finally, we demonstrate that concurrent sequences interact reliably, generating a highly combinatorial space of sequence activations. Our results reveal the impact of individual spikes in cortical circuits, detailing how repeatable sequences of activity can be triggered, sustained, and controlled during cortical computations.}, } @article {pmid36776446, year = {2023}, author = {Carrera, JS and Bailey, S and Wiggins, R and Watkins, C and Sullivan, L and Mays, M and Key, K}, title = {Community Science as Resistance to Neoliberal Scientific Praxis.}, journal = {Environmental justice (Print)}, volume = {16}, number = {1}, pages = {54-61}, doi = {10.1089/env.2021.0099}, pmid = {36776446}, issn = {1939-4071}, abstract = {BACKGROUND: Flint is a site of resistance to neoliberalism specifically because of the actions of Flint residents. The impacts of this organizing are due, in part, to sustained efforts to reimagine how communities can contribute to scientific knowledge production. We argue that Flint residents' efforts to advance a community-driven research (CDR) agenda represent an important and successful resistance to neoliberal scientific regulatory practices.

METHODS: We present Flint as a case study in CDR as a form of resistance. This article uses participatory observation within community-based research and draws from the personal experiences of the research team as long-term and lifelong residents of Flint who were actively involved in different aspects of community mobilizing during the water crisis.

CASE STUDY: We highlight Flint's rich and sustained community-based participatory research history, resident-led data collection efforts to assess the environmental and health conditions, a resident-led effort to tell the story of the water crisis from the residents' perspective, and recent efforts to develop and advance a CDR model.

DISCUSSION: Community-led research efforts in Flint follow Leitner et al.'s typology of contesting neoliberalism through opting in to neoliberal science to advance community needs, collecting data to support direct opposition through protest and mobilization, creating alternative knowledge frames, and using CDR to disengage from the traditional scientific model.

CONCLUSIONS: Through CDR, Flint residents work in direct resistance to the tacit integration of neoliberal values into science and alternatively advance community organizing as a key aspect of science toward environmental justice.}, } @article {pmid36761452, year = {2022}, author = {Sharkey, MJ and Tucker, EM and Baker, A and Smith, MA and Ratnasingham, S and Manjunath, R and Hebert, P and Hallwachs, W and Janzen, D}, title = {More discussion of minimalist species descriptions and clarifying some misconceptions contained in Meier et al. 2021.}, journal = {ZooKeys}, volume = {1110}, number = {}, pages = {135-149}, pmid = {36761452}, issn = {1313-2989}, abstract = {This is a response to a preprint version of "A re-analysis of the data in Sharkey et al.'s (2021) minimalist revision reveals that BINs do not deserve names, but BOLD Systems needs a stronger commitment to open science", https://www.biorxiv.org/content/10.1101/2021.04.28.441626v2. Meier et al. strongly criticized Sharkey et al.'s publication in which 403 new species were deliberately minimally described, based primarily on COI barcode sequence data. Here we respond to these criticisms. The following points are made: 1) Sharkey et al. did not equate BINs with species, as demonstrated in several examples in which multiple species were found to be in single BINs. 2) We reiterate that BINs were used as a preliminary sorting tool, just as preliminary morphological identification commonly sorts specimens based on color and size into unit trays; despite BINs and species concepts matching well over 90% of species, this matching does not equate to equality. 3) Consensus barcodes were used only to provide a diagnosis to conform to the rules of the International Code of Zoological Nomenclature just as consensus morphological diagnoses are. The barcode of a holotype is definitive and simply part of its cellular morphology. 4) Minimalist revisions will facilitate and accelerate future taxonomic research, not hinder it. 5) We refute the claim that the BOLD sequences of Plesiocoelusvanachterbergi are pseudogenes and demonstrate that they simply represent a frameshift mutation. 6) We reassert our observation that morphological evidence alone is insufficient to recognize species within species-rich higher taxa and that its usefulness lies in character states that are congruent with molecular data. 7) We show that in the cases in which COI barcodes code for the same amino acids in different putative species, data from morphology, host specificity, and other ecological traits reaffirm their utility as indicators of genetically distinct lineages.}, } @article {pmid36747293, year = {2023}, author = {Vandervelde, S and Vlaeyen, E and de Casterlé, BD and Flamaing, J and Valy, S and Meurrens, J and Poels, J and Himpe, M and Belaen, G and Milisen, K}, title = {Strategies to implement multifactorial falls prevention interventions in community-dwelling older persons: a systematic review.}, journal = {Implementation science : IS}, volume = {18}, number = {1}, pages = {4}, pmid = {36747293}, issn = {1748-5908}, mesh = {Humans ; Aged ; Aged, 80 and over ; *Independent Living ; *Health Personnel ; }, abstract = {BACKGROUND: One-third of the community-dwelling older persons fall annually. Guidelines recommend the use of multifactorial falls prevention interventions. However, these interventions are difficult to implement into the community. This systematic review aimed to explore strategies used to implement multifactorial falls prevention interventions into the community.

METHODS: A systematic search in PubMed (including MEDLINE), CINAHL (EBSCO), Embase, Web of Science (core collection), and Cochrane Library was performed and updated on the 25th of August, 2022. Studies reporting on the evaluation of implementation strategies for multifactorial falls prevention interventions in the community setting were included. Two reviewers independently performed the search, screening, data extraction, and synthesis process (PRISMA flow diagram). The quality of the included reports was appraised by means of a sensitivity analysis, assessing the relevance to the research question and the methodological quality (Mixed Method Appraisal Tool). Implementation strategies were reported according to Proctor et al.'s (2013) guideline for specifying and reporting implementation strategies and the Taxonomy of Behavioral Change Methods of Kok et al. (2016).

RESULTS: Twenty-three reports (eighteen studies) met the inclusion criteria, of which fourteen reports scored high and nine moderate on the sensitivity analysis. All studies combined implementation strategies, addressing different determinants. The most frequently used implementation strategies at individual level were "tailoring," "active learning," "personalize risk," "individualization," "consciousness raising," and "participation." At environmental level, the most often described strategies were "technical assistance," "use of lay health workers, peer education," "increasing stakeholder influence," and "forming coalitions." The included studies did not describe the implementation strategies in detail, and a variety of labels for implementation strategies were used. Twelve studies used implementation theories, models, and frameworks; no studies described neither the use of a determinant framework nor how the implementation strategy targeted influencing factors.

CONCLUSIONS: This review highlights gaps in the detailed description of implementation strategies and the effective use of implementation frameworks, models, and theories. The review found that studies mainly focused on implementation strategies at the level of the older person and healthcare professional, emphasizing the importance of "tailoring," "consciousness raising," and "participation" in the implementation process. Studies describing implementation strategies at the level of the organization, community, and policy/society show that "technical assistance," "actively involving stakeholders," and "forming coalitions" are important strategies.

TRIAL REGISTRATION: PROSPERO CRD42020187450.}, } @article {pmid36744835, year = {2023}, author = {Nielsen, M and Watter, K and Bohan, J and Kennedy, A}, title = {Implementation and modification of a service model for community transitional rehabilitation for people with acquired brain injury.}, journal = {Brain injury}, volume = {37}, number = {5}, pages = {446-456}, doi = {10.1080/02699052.2022.2163292}, pmid = {36744835}, issn = {1362-301X}, mesh = {Humans ; Pilot Projects ; *Brain Injuries/rehabilitation ; Australia ; }, abstract = {To examine the implementation of a novel Acquired Brain Injury (ABI) Transition-Specific Service Model in Queensland, Australia to explore its potential for successful operationalization in a clinical context and what, if any, modifications were indicated. This study is part of a larger evaluation of the ABI Transitional Rehabilitation Service (ABITRS) Pilot Project using a Hybrid Type 1 research design. Data was drawn from a process evaluation nested within the larger study. Stirman et al.'s FRAME guided assessment of modifications made to the proposed Transition-Specific Service Model during implementation. The proposed Transition-Specific Service Model provided a foundational framework for establishing an ABI transitional rehabilitation service in Queensland. All designated key service delivery features of the model were implemented; context and content modifications occurred in response to the implementation experience. Priority areas for intervention were comprehensively addressed, with significant changes made to the proposed staffing profile to address an identified need for more senior clinicians. The ABITRS Pilot Project provided an opportunity to test and refine elements of an ABI Transition-Specific Service Model in a clinical context. Knowledge gained from this process has the potential to inform future design of transitional rehabilitation services for acquired brain injury.}, } @article {pmid36740956, year = {2023}, author = {Green, BB}, title = {Defensive information processing and nonadherence to health-protective behaviors.}, journal = {Cancer}, volume = {129}, number = {8}, pages = {1156-1158}, doi = {10.1002/cncr.34602}, pmid = {36740956}, issn = {1097-0142}, mesh = {Humans ; *Mass Screening ; *Colorectal Neoplasms/diagnosis/prevention & control ; Health Behavior ; Occult Blood ; Early Detection of Cancer ; }, abstract = {In this issue of Cancer, Clarke et al. measure defensive information processing (DIP) to avoid fecal immunochemical testing for colorectal cancer. DIP is a way of reducing the negative psychological effects of threats such as cancer and may influence health-protective behaviors such as the completion of recommended cancer screening. This editorial complements Clarke et al.'s study with a discussion of interventions for decreasing DIP around cancer screening and other health-protective recommendations.}, } @article {pmid36720719, year = {2023}, author = {Lehmann, RJB and Schäfer, T and Helmus, LM and Henniges, J and Fleischhauer, M}, title = {Same Score, Different Audience, Different Message: Perceptions of Sex Offense Risk Depend on Static-99R Risk Level and Personality Factors of the Recipient.}, journal = {Sexual abuse : a journal of research and treatment}, volume = {35}, number = {7}, pages = {863-895}, doi = {10.1177/10790632221148667}, pmid = {36720719}, issn = {1573-286X}, mesh = {Humans ; Risk Assessment/methods ; *Criminals/psychology ; Prospective Studies ; *Sex Offenses/psychology ; Personality ; }, abstract = {There are multiple ways to report risk scale results. Varela et al. (2014) found that Static-99R results were interpreted differently by prospective jurors based on risk level (high vs low) and an interaction between risk level and risk communication format (categorical, absolute estimate, and risk ratio). We adapted and extended Varela et al.'s (2014) study using updated Static-99R norms, recruiting a population-wide sample (n = 166), and adding variables assessing the personality factors 'cognitive motivation' (i.e., need for cognition) and 'attitudinal affect' (i.e., attitudes toward sex offenders, authoritarianism). We found a main effect of risk level and no effect of either communication format or the interaction between the two. Adding the personality variables increased explained variance from 9% to 34%, suggesting risk perception may be more about the personality of the person receiving the information than the information itself. We also found an interaction between attitudes toward sex offenders and risk level. Our results suggest risk perception might be better understood if personality factors are considered, particularly attitudes toward sex offenders. Because biases/personality of the person receiving the information are unknown in real world settings we argue that sharing multiple methods for communicating risk might be best and more inclusive.}, } @article {pmid36708418, year = {2023}, author = {Murakami, S and Kohmura, Y and Someya, Y and Suzuki, K and Inoue, K and Amano, S and Aoki, K}, title = {Prevalence of dry eye syndrome and risk factors in physical education and sports science graduates.}, journal = {Japanese journal of ophthalmology}, volume = {67}, number = {2}, pages = {175-181}, pmid = {36708418}, issn = {1613-2246}, support = {Joint Research Program of Juntendo University Faculty of Health and Sports Science//Joint Research Program of Juntendo University Faculty of Health and Sports Science/ ; Institute of Health and Sports Science & Medicine, Juntendo University//Institute of Health and Sports Science & Medicine, Juntendo University/ ; }, mesh = {Male ; Humans ; Female ; *Quality of Life ; Cross-Sectional Studies ; Prevalence ; Physical Education and Training ; *Dry Eye Syndromes/diagnosis/epidemiology ; Risk Factors ; Surveys and Questionnaires ; }, abstract = {PURPOSE: There are only a few epidemiological studies of dry eye syndrome (DES) in populations with a common academic background. in this study, the prevalence of DES and associated factors were evaluated separately in men and women physical education and sports science graduates.

STUDY DESIGN: Cross-sectional survey.

METHODS: A questionnaire about the diagnosis of DES and associated factors was mailed to 9507 graduates of the Faculty of Health and Sports Science, Juntendo University. The questions covered subjective DES using Schaumberg et al.'s questionnaire and the prevalence of diagnosed DES. Associated factors, age, sex, smoking, alcohol consumption, body mass index, daily screen viewing time, and contact lens (CL) use were analyzed.

RESULTS: A total of 2048 valid responses were received. The prevalence of diagnosed DES was 2.9% in men and 9.3% in women. For subjective DES, the prevalence was 14.8% in men and 39.8% in women. The odds ratio for DES was high in men and women who used CLs and women whose daily screen viewing time was ≥ 4 h.

CONCLUSION: Both diagnosed and subjective DES were highly prevalent in men and women of all ages, particularly among those in their 20 and 30s. CL use was associated with DES in both men and women. Measures to deal with the factors that can be corrected might have a positive effect on the ocular health and quality of life of physical education and sports science graduates.}, } @article {pmid36703799, year = {2023}, author = {Houldsworth, C and Nair, KPS and Hariharan, RP}, title = {Cognition and Quality of Life of People with Spinal Cord Injury.}, journal = {Progress in rehabilitation medicine}, volume = {8}, number = {}, pages = {20230001}, pmid = {36703799}, issn = {2432-1354}, abstract = {OBJECTIVES: The aim of this study was to assess the cognitive abilities of people with spinal cord injury (SCI) using the Edinburgh Cognitive and Behavior Amyotrophic Lateral Sclerosis Screen (ECAS), a tool designed for testing cognition in individuals with limited hand motor function. The impact of cognitive dysfunction on quality of life was also assessed.

METHODS: Forty-one patients with SCI were assessed using ECAS, the brief version of the World Health Organisation Quality of Life questionnaire (WHOQOL-BREF), and the Spinal Cord Independence Measure.

RESULTS: Overall, 28 of the 41 participants scored below the cut-off threshold for normal population in ECAS. The domains affected were language, 63%; memory, 51%; executive function, 44%; verbal fluency, 44%; and visuospatial skills, 24%. On multiple regression analysis, the ECAS total score moderately strongly explained the variance in the WHOQOL-BREF psychological (β = 0.428, t = 2.958, P = 0.005) and environmental (β = 0.411, t = 2.819, P = 0.008) domains. ECAS memory scores independently influenced WHOQOL-BREF physical (β = 0.398, t = 2.67, P = 0.011) and environmental (β = 0.37, t = 2.697, P = 0.010) domains. WHOQOL-BREF psychological scores were significantly influenced by ECAS executive scores (β = 0.415, t = 2.85, P = 0.007), whereas the social domain was not significantly influenced by ECAS scores.

CONCLUSIONS: It was feasible to use ECAS in individuals with SCI. Cognitive ability influenced the quality of life of people with SCI.}, } @article {pmid36702767, year = {2023}, author = {Plaisime, MV}, title = {Invited Commentary: Undiagnosed and Undertreated-the Suffocating Consequences of the Use of Racially Biased Medical Devices During the COVID-19 Pandemic.}, journal = {American journal of epidemiology}, volume = {192}, number = {5}, pages = {714-719}, pmid = {36702767}, issn = {1476-6256}, mesh = {Humans ; Black or African American ; *COVID-19 ; Oximetry/methods ; Pandemics ; *Racism ; *Equipment and Supplies ; }, abstract = {While medical technology is typically considered neutral, many devices rely upon racially biased algorithms that prioritize care for White patients over Black patients, who may require more urgent medical attention. In their accompanying article, Sudat et al. (Am J Epidemiol. 2023;XXX(XX):XXX-XXX) document striking inaccuracies in pulse oximeter readings among Black patients, with significant clinical implications. Their findings suggest that this resulted in racial differences in delivery of evidence-based care during the coronavirus disease 2019 (COVID-19) pandemic, affecting admissions and treatment protocols. Despite the medical community's growing awareness of the pulse oximeter's significant design flaw, the device is still in use. In this article, I contextualize Sudat et al.'s study results within the larger history of racial bias in medical devices by highlighting the consequences of the continued underrepresentation of diverse populations in clinical trials. I probe the implications of racially biased assessments within clinical practice and research and illustrate the disproportionate impact on patients of color by examining 2 medical tools, the pulse oximeter and pulmonary function tests. Both cases result in the undertreatment and underdiagnosis of Black patients. I also demonstrate how the social underpinnings of racial bias in medical technology contribute to poor health outcomes and reproduce health disparities, and propose several recommendations for the field to rectify the harms of racial bias in medical technology.}, } @article {pmid36689888, year = {2023}, author = {Tabri, N and J A Wohl, M}, title = {There is (still) a global factor that underlies the PGSI: A reanalysis of Tseng, Flack, Caudwell, and Stevens (2023).}, journal = {Addictive behaviors}, volume = {140}, number = {}, pages = {107623}, doi = {10.1016/j.addbeh.2023.107623}, pmid = {36689888}, issn = {1873-6327}, mesh = {Humans ; *Gambling ; Severity of Illness Index ; Australia/epidemiology ; *Problem Behavior ; Factor Analysis, Statistical ; *Behavior, Addictive ; }, abstract = {Tseng, Flack, Caudwell, and Stevens (2023) conducted confirmatory factor analyses (CFA) of the Problem Gambling Severity Index (PGSI)-a gold-standard measure of disordered gambling symptomatology that has traditionally been indexed using a total score-with data from a large representative sample of Australians residing in Northern Territory who gamble (N = 3,740). Based on their results, Tseng et al. argued that a two-factor model best fit the data and so the PGSI items could be separated into two subscales: Problem Behaviours and Consequences of Problem Behaviours. We reanalyzed their data using CFA and found that a hierarchical model provided the best fit to the data. The hierarchical model includes a global factor underlying all PGSI items and two sub factors that correspond to the PGSI items assessing behaviours and consequences. The global factor was empirically well-defined, but the behaviours and consequences sub factors were not. Also, the two sub factors did not reliably measure the more narrowly defined behaviours and consequences constructs independent of the global factor. Based on our reanalyses of Tseng et al.'s (2023) data, we encourage researchers in the field of gambling studies to continue using the PGSI total score as an index of disordered gambling symptomatology.}, } @article {pmid36685717, year = {2023}, author = {Kamoche, K and Wood, G}, title = {International business and Africa: Theoretical and applied challenges, and future directions.}, journal = {Journal of international business studies}, volume = {}, number = {}, pages = {1-12}, pmid = {36685717}, issn = {0047-2506}, abstract = {In response to Nachum et al.'s (J Int Bus Stud, 2023) call for further research in Africa by international business (IB) scholars, we argue that while IB scholars may have been slow to engage with Africa, the same cannot be said of related and IB-relevant business and management scholarship. There is already a substantial body of work on Africa in other domains of business and management scholarship - and relevant theorizing - that represents an important resource for IB scholarship. In contextualizing the 'interesting', we identify several contemporary theoretical strands that have so far characterized 'Africa research', interrogate ongoing challenges that mitigate these efforts, and suggest ways in which further research that speaks to theoretical, practical, and policy issues might inform IB researchers' engagement with Africa. Specifically, we set out the broader scope of the African business/management debate that might inform IB research, re-examine African diversity through the prism of 'theoretical tensions and puzzles', and consider the role of emergent indigenous theorizing such as ubuntu and Africapitalism that make Africa both 'interesting' and worthy of IB inquiry.}, } @article {pmid36682070, year = {2023}, author = {Lee, AT and Chin, P and Nambiar, A and Hill Haskins, N}, title = {Addressing intergenerational trauma in Black families: Trauma-informed socioculturally attuned family therapy.}, journal = {Journal of marital and family therapy}, volume = {49}, number = {2}, pages = {447-462}, doi = {10.1111/jmft.12632}, pmid = {36682070}, issn = {1752-0606}, mesh = {Humans ; *Historical Trauma ; Family Therapy ; Mental Health ; *Adverse Childhood Experiences ; }, abstract = {Increased attention to the prevalence and impact of traumatic experiences have been highlighted within the mental health field since Felitti et al.'s study of adverse childhood experiences. Black communities experience traumatic events at a higher rate than other racial groups. The phenomena of historical trauma, race-based trauma, and intergenerational trauma have been speculated to be reasons for this discrepancy. In this article, the authors explore factors that compound the traumatic experiences of Black communities, review socioculturally attuned family therapy and trauma-informed care, and propose an approach to addressing intergenerational trauma in Black families that integrates socioculturally attuned family therapy and trauma-informed care.}, } @article {pmid36680965, year = {2023}, author = {Fallon, B and Joh-Carnella, N and Houston, E and Livingston, E and Trocmé, N}, title = {The more we change the more we stay the same: Canadian child welfare systems' response to child well-being.}, journal = {Child abuse & neglect}, volume = {137}, number = {}, pages = {106031}, doi = {10.1016/j.chiabu.2023.106031}, pmid = {36680965}, issn = {1873-7757}, mesh = {Child ; Humans ; *Child Health ; Canada/epidemiology ; Child Welfare ; *Child Abuse/prevention & control ; Cohort Studies ; }, abstract = {BACKGROUND: Child welfare services in Canada are guided by a dual mandate: to protect children from imminent harm and to promote their optimal development and well-being. To understand how child welfare systems respond to this dual mandate, Trocmé et al. (2014) developed a taxonomy to classify child welfare investigations as either being related to urgent protection or chronic needs.

OBJECTIVE: To extend Trocmé et al.'s (2014) analysis using data from the Canadian Incidence Study of Reported Child Abuse and Neglect 2019 (CIS-2019).

PARTICIPANTS AND SETTING: The CIS-2019 employs a file review methodology to collect information on child maltreatment-related investigations conducted in Canada in 2019. The study's unweighted sample included 41,948 investigations involving children aged 0-15 years.

METHODS: Secondary analyses of the CIS-2019 were conducted including frequency counts and bivariate analyses.

RESULTS: Ninety percent of investigations conducted in Canada in 2019 were focused on concerns related to chronic needs. Most investigations (90.9 % of urgent protection investigations and 98.3 % of chronic needs investigations) did not involve physical harm to the child. Urgent protection investigations were less likely to have been previously investigated and more likely to be substantiated, involve a child welfare court application, or involve a placement in out-of-home care.

CONCLUSIONS: Most child welfare investigations in Canada continue to be focused on chronic needs. Yet, the investigation response seems designed to respond to urgent protection concerns. A truly differential model is needed to appropriately respond to the dual mandate of Canadian child welfare services and better serve children and families.}, } @article {pmid36670213, year = {2023}, author = {Eyni, S and Hashemi, Z and Mousavi, SE and Taghavi, R}, title = {Spirituality, Trait Gratitude, and Post-Traumatic Growth in Iranian Veterans with PTSD: The Mediating Role of Ego Resilience.}, journal = {Journal of religion and health}, volume = {62}, number = {6}, pages = {4072-4087}, pmid = {36670213}, issn = {1573-6571}, mesh = {Humans ; *Stress Disorders, Post-Traumatic/psychology ; *Veterans/psychology ; Iran ; Spirituality ; *Posttraumatic Growth, Psychological ; *Resilience, Psychological ; Ego ; }, abstract = {In Iran, spirituality is one of the most critical factors affecting veterans' health. The present study aimed to determine the mediating role of ego resilience in the relationship between spirituality and trait gratitude with post-traumatic growth in Iranian veterans with PTSD. In the present descriptive and correlational study, 300 veterans with PTSD were hospitalized and treated at Isar Psychiatric Hospital in Ardabil in 2021 and were selected as the sample. Data were collected using Tedeschi and Calhoun's Traumatic Developmental Questionnaire, Parsian and Dunning, Mc Cullough et al.'s Trait Gratitude Questionnaire, and Block et al.'s Ego Resilience Questionnaire. Based on the obtained results and various fit indices, the direct and indirect relationships between spirituality, trait gratitude, ego resilience, and post-traumatic growth in veterans with post-traumatic stress disorder were confirmed (p < 0.01). Also, spirituality and trait gratitude through ego resilience indirectly affected the post-traumatic growth of veterans with PTSD (P < 0.05). Thus, targeting these three components through psychological therapies may effectively increase post-traumatic growth in veterans experiencing trauma.}, } @article {pmid36669446, year = {2023}, author = {Hadden, LM and Penny, H and Jones, AL and Partridge, AM and Lancaster, TM and Allen, C}, title = {Pre-frontal stimulation does not reliably increase reward responsiveness.}, journal = {Cortex; a journal devoted to the study of the nervous system and behavior}, volume = {159}, number = {}, pages = {268-285}, pmid = {36669446}, issn = {1973-8102}, support = {/WT_/Wellcome Trust/United Kingdom ; 104943/Z/14/Z/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Humans ; Reproducibility of Results ; *Transcranial Magnetic Stimulation ; *Learning ; Treatment Outcome ; Reward ; }, abstract = {Depression is the leading cause of disability worldwide and its effects can be fatal, with over 800,000 people dying by suicide each year. Neuromodulatory treatments such as transcranial magnetic stimulation (TMS) are being used to treat depression. Despite its endorsement by two regulatory bodies: NICE (2016) and the FDA (2008), there are major questions about the treatment efficacy and biological mechanisms of TMS. Ahn et al.'s (2013) justified the use of TMS in a clinical context in an important study indicating that excitatory TMS increases reward responsiveness. A pseudo-replication of this study by Duprat et al., (2016) also found a similar effect of active TMS, but only with the addition of an exploratory covariate to the analyses-trait reward responsiveness. Here we replicate Ahn et al.'s (2013) key study, and to test the reliability of the effects, and their dependency on trait reward responsiveness as described by Duprat et al., (2016). Using excitatory and sham TMS, we tested volunteers using the probabilistic learning task to measure their reward responsiveness both before and after stimulation. We also examined affect (positive, negative) following stimulation. Irrespective of TMS, the task was shown to be sensitive to reward responsiveness. However, we did not show TMS to be effective in increasing reward responsiveness and we did not replicate Ahn et al., (2013) or Duprat et al., (2016)'s key findings for TMS efficacy, where we provide evidence favouring the null. Moreover, exploratory analyses suggested following active stimulation, positive affect was reduced. Given our findings, we question the basic effects, which support the use of TMS for depression, particularly considering potential deleterious effects of reduced positive affect in patients with depression.}, } @article {pmid36656123, year = {2023}, author = {Mohamed, FF and Ge, C and Hallett, SA and Bancroft, AC and Cowling, RT and Ono, N and Binrayes, AA and Greenberg, B and Levi, B and Kaartinen, VM and Franceschi, RT}, title = {Control of craniofacial development by the collagen receptor, discoidin domain receptor 2.}, journal = {eLife}, volume = {12}, number = {}, pages = {}, pmid = {36656123}, issn = {2050-084X}, support = {P30AR069620/AR/NIAMS NIH HHS/United States ; R01DE11723/DE/NIDCR NIH HHS/United States ; R21DE029012/DE/NIDCR NIH HHS/United States ; R01DE029465/DE/NIDCR NIH HHS/United States ; R01 DE011723/DE/NIDCR NIH HHS/United States ; R01 AR078324/AR/NIAMS NIH HHS/United States ; R21 DE029012/DE/NIDCR NIH HHS/United States ; R01 DE029465/DE/NIDCR NIH HHS/United States ; R56 DE011723/DE/NIDCR NIH HHS/United States ; P30 AR069620/AR/NIAMS NIH HHS/United States ; R01AR078324/AR/NIAMS NIH HHS/United States ; }, mesh = {Animals ; Humans ; Mice ; Cartilage ; Chondrocytes/physiology ; Collagen ; *Discoidin Domain Receptor 2/genetics ; Receptors, Collagen ; }, abstract = {Development of the craniofacial skeleton requires interactions between progenitor cells and the collagen-rich extracellular matrix (ECM). The mediators of these interactions are not well-defined. Mutations in the discoidin domain receptor 2 gene (DDR2), which encodes a non-integrin collagen receptor, are associated with human craniofacial abnormalities, such as midface hypoplasia and open fontanels. However, the exact role of this gene in craniofacial morphogenesis is not known. As will be shown, Ddr2-deficient mice exhibit defects in craniofacial bones including impaired calvarial growth and frontal suture formation, cranial base hypoplasia due to aberrant chondrogenesis and delayed ossification at growth plate synchondroses. These defects were associated with abnormal collagen fibril organization, chondrocyte proliferation and polarization. As established by localization and lineage-tracing studies, Ddr2 is expressed in progenitor cell-enriched craniofacial regions including sutures and synchondrosis resting zone cartilage, overlapping with GLI1 + cells, and contributing to chondrogenic and osteogenic lineages during skull growth. Tissue-specific knockouts further established the requirement for Ddr2 in GLI +skeletal progenitors and chondrocytes. These studies establish a cellular basis for regulation of craniofacial morphogenesis by this understudied collagen receptor and suggest that DDR2 is necessary for proper collagen organization, chondrocyte proliferation, and orientation.}, } @article {pmid36655908, year = {2023}, author = {Monteiro, N}, title = {Mom and dad are not that different after all: Immune modulation as a prerequisite for the evolution of pregnancy.}, journal = {Molecular ecology}, volume = {32}, number = {4}, pages = {753-755}, pmid = {36655908}, issn = {1365-294X}, mesh = {Animals ; Male ; Pregnancy ; Female ; *Biological Evolution ; *Reproduction/genetics ; Ecology ; Transcriptome ; Oviparity ; Mammals/genetics ; }, abstract = {Pregnancy, the post-fertilization period when embryos are incubated within the body, is a dynamic multistage process that has convergently evolved in many vertebrates. To increase independence from environmental fluctuations and protect offspring from predation, challenges had to be initially overcome. The most obvious, when considering such an intimate relationship between the parent and its semi-allogenic offspring, was the pressing need to dodge immunity-associated embryo rejection. In mammals, immunological tolerance was found to be dependent on the active modulation of the immune system. Even though supporting much of the current knowledge on vertebrate pregnancy, mammals lack extant transitional stages that could help reconstruct the evolutionary pathway of this fascinatingly complex reproduction mode. In this issue of Molecular Ecology, Parker et al. selected an untraditional model-the seahorse and pipefish family, whose species evolved male pregnancy across an almost continuous gradient of complexity, from external oviparity to internal gestation. By contrasting gene expression profiles of syngnathids with distinct brooding architectures, this study allowed for the observation of subtle evolutionary adaptations, while confirming the existence of remarkable similarities to "female" pregnancy (e.g., the evolution of male pregnancy in pouched species occurred alongside immune downregulation, and inflammation seems vital during early pregnancy stages). In a world where the debate on sex-roles takes centre stage, Parker et al.'s appeasing results hint at the fact that the strongly convergent evolution of vertebrate pregnancy was seemingly unaffected by which sex carries the burden of gestation.}, } @article {pmid36649163, year = {2024}, author = {Morales, J and Firestone, C}, title = {Empirical evidence for perspectival similarity.}, journal = {Psychological review}, volume = {131}, number = {1}, pages = {311-320}, doi = {10.1037/rev0000403}, pmid = {36649163}, issn = {1939-1471}, support = {//National Science Foundation/ ; }, abstract = {When a circular coin is rotated in depth, is there any sense in which it comes to resemble an ellipse? While this question is at the center of a rich and divided philosophical tradition (with some scholars answering affirmatively and some negatively), Morales et al. (2020, 2021) took an empirical approach, reporting 10 experiments whose results favor such perspectival similarity. Recently, Burge and Burge (2022) offered a vigorous critique of this work, objecting to its approach and conclusions on both philosophical and empirical grounds. Here, we answer these objections on both fronts. We show that Burge and Burge's critique rests on misunderstandings of Morales et al.'s claims; of the relation between the data and conclusions; and of the philosophical context in which the work appears. Specifically, Burge and Burge attribute to us a much stronger (and stranger) view than we hold, involving the introduction of "a new entity" located "in some intermediate position(s) between the distal shape and the retinal image." We do not hold this view. Indeed, once properly understood, most of Burge and Burge's objections favor Morales et al.'s claims rather than oppose them. Finally, we discuss several questions that remain unanswered, and reflect on a productive path forward on these issues of foundational scientific and philosophical interest. (PsycInfo Database Record (c) 2024 APA, all rights reserved).}, } @article {pmid36647370, year = {2023}, author = {Khalfaoui, R and Mefteh-Wali, S and Dogan, B and Ghosh, S}, title = {Extreme spillover effect of COVID-19 pandemic-related news and cryptocurrencies on green bond markets: A quantile connectedness analysis.}, journal = {International review of financial analysis}, volume = {86}, number = {}, pages = {102496}, pmid = {36647370}, issn = {1873-8079}, abstract = {We provide the first empirical study on the role of panic and stress related to the COVID-19 pandemic, including six uncertainties and the four most traded cryptocurrencies, on three green bond market volatilities. Based on daily data covering the period from January 1, 2020 to January 31, 2022, we combine Diebold and Yilmaz's (2012, 2014) time domain spillover approach and Ando et al.'s (2022) quantile regression framework to investigate the time-frequency spillover connectedness among markets and measure the direction and intensity of the net transmission effect under extreme negative and positive event conditions, and normal states. We further provide novel insights into the green finance literature by examining sensitivity to quantile analysis of the net transfer mechanism between green bonds, cryptocurrencies, and pandemic uncertainty. Regarding the network connectedness analysis, the results reveal strong net information spillover transmission among markets under the bearish market. In extremely negative event circumstances, the MSCI Euro green bond acts as the leading net shock receiver in the system, whereas COVID-19 fake news appears as the largest net shock contributor, followed by BTC. According to sensitivity to quantile analysis, the net dynamic shock transfer mechanism is time-varying and quantile-dependent. Overall, our work uncovers crucial implications for investors and policymakers.}, } @article {pmid36645495, year = {2023}, author = {García-Mansilla, A and Castro Lalín, A and Holc, F and Molho, NM and Vescovo, A and Slullitel, PA and Buttaro, MA}, title = {Intraoperative unfractionated heparin before femoral component cementation should be avoided in femoral neck fracture treated with hybrid total hip arthroplasty.}, journal = {European journal of orthopaedic surgery & traumatology : orthopedie traumatologie}, volume = {33}, number = {6}, pages = {2547-2554}, pmid = {36645495}, issn = {1432-1068}, mesh = {Humans ; Heparin/adverse effects ; *Arthroplasty, Replacement, Hip/adverse effects ; Cementation ; Anticoagulants/adverse effects ; *Thromboembolism/etiology ; *Femoral Neck Fractures ; }, abstract = {PURPOSE: To compare the incidence of perioperative thromboembolic events in femoral neck fracture (FNF) patients treated with hybrid total hip arthroplasty (THA) with intraoperative unfractionated heparin (UFH) versus a control group without intraoperative UFH before femoral component cementation.

METHODS: We compared 139 cases without UFH (group A) versus 134 who received 10 UI/kg UFH (group B). Indication of UFH before cementation depended on the preferences of the anaesthesiologists in each case. We assessed intraoperative bone cement implantation syndrome (BCIS) and 30-day thromboembolic events, and 90-day and 1-year mortality. BCIS was classified as per Donaldson et al.'s classification according to the degree of hypotension, arterial desaturation or loss of consciousness.

RESULTS: BCIS was observed in 51 (18%) cases, including 37 (13%) grade 1 and 14 (5%) grade 2. Forty-seven BCISs (35%) were observed in group B and 4 (3%) in group A (p < 0.001). Multivariate regression showed that intraoperative UFH (OR = 18, CI 95% 6-52) and consumption of oral anticoagulants (OR = 3.3, CI 95% 1-10) increased the risk of BCIS. Five patients further developed a 30-day pulmonary embolism in group B, while 2 presented this complication in group A (p = 0.231). No association between BCIS and 30-day thromboembolic events was found (p = 0.62). 90-day (1% each, p = 0.98) and 1-year (2% vs. 3%, p = 0.38) mortality were similar.

CONCLUSIONS: BCIS was a frequent finding in FNF patients treated with hybrid THA. We found a paradoxically significant increase in BCIS with the use of UFH. Heparin did not seem to prevent BCIS, other thromboembolic events and mortality in this group of patients.}, } @article {pmid36645456, year = {2023}, author = {Jo, W and Park, HJ and Kim, JN and Kim, MS and Shin, H and Kang, CH}, title = {Aponeurotic expansion of the supraspinatus tendon and concomitant shoulder pathologies.}, journal = {European radiology}, volume = {33}, number = {7}, pages = {4782-4788}, pmid = {36645456}, issn = {1432-1084}, mesh = {Humans ; Rotator Cuff/pathology ; Shoulder ; *Tendon Injuries/diagnostic imaging/epidemiology ; Retrospective Studies ; Aponeurosis/pathology ; *Rotator Cuff Injuries/complications/diagnostic imaging/epidemiology ; Tendons/pathology ; Rupture ; Magnetic Resonance Imaging/methods ; *Tendinopathy/complications/diagnostic imaging/epidemiology ; }, abstract = {OBJECTIVES: We investigated the correlation of aponeurotic expansion of the supraspinatus tendon (AESST) with shoulder pathologies such as long head of biceps tendon (LHB), supraspinatus tendon (SST), and subscapularis tendon (SSc).

METHODS: We retrospectively evaluated 47 healthy patients and 163 patients with shoulder symptoms from August 2014 to March 2021. First, the presence of AESST was evaluated based on Moser et al.'s classification. Second, the presence of abnormal findings of including LHB tendinitis, LHB subluxation, SST tendinitis, SST tear, SSc tendinitis, and SSc tendon tear was evaluated. We analyzed the prevalence and type of AESST between the two study groups and the relationship between abnormal findings and the presence of AESST.

RESULTS: The prevalence of AESST for readers 1 and 2 was 26.1% and 30.4% in the asymptomatic group, respectively, and 22.8% and 31.3% in the symptomatic group. Type 1 was most common (17.3-23.9%) followed by types 2a and 2b. There were no significant differences in the distribution of aponeurosis type between the two groups. In the AESST-positive groups, 45.9% and 47.1% had SST tears on examination by readers 1 and 2, respectively, whereas only 26.4% and 27.9% had SST tears in the AESST-negative group suggesting AESST is associated with SST tear. The odds ratio for SST tear in the presence of AESST was 2.370 and 2.294 (readers 1 and 2).

CONCLUSIONS: There is an association between SST tears and the presence of AESST.

KEY POINTS: • We evaluated the prevalence of aponeurotic expansion of the supraspinatus tendon (AESST) on MR imaging by type in both symptomatic and asymptomatic groups. • We investigated the correlation of AESST with shoulder pathologies such as biceps tendon and supraspinatus tendon tears. • There is an association between SST tears and the presence of AESST. • Radiologists should be aware of the risk of rotator cuff pathology if AESST is detected.}, } @article {pmid36643384, year = {2022}, author = {Domínguez, DG and Cheng, HL and De La Rue, L}, title = {Career Barriers and Coping Efficacy with International Students in Counseling Psychology Programs.}, journal = {The Counseling psychologist}, volume = {50}, number = {6}, pages = {780-812}, pmid = {36643384}, issn = {0011-0000}, support = {R25 DA035692/DA/NIDA NIH HHS/United States ; }, abstract = {This study uses Lent et al.'s (1994) social cognitive career theory (SCCT) as a framework for understanding the career barriers and coping efficacy experienced by international master's of counseling psychology students. Grounded in SCCT, we described coping efficacy as international students' perceived capability to navigate career barriers. Using Braun and Clarke's (2006) thematic analysis, we explored the career barriers and coping efficacy of 12 international master's of counseling psychology students. The first focus area, International Journey with Multiple Barriers, included five themes: Interpersonal Stress, Language Barriers, Financial Pressures, Advising Concerns, and Visa and Immigration-Related Stress. The second focus area, Agents of Change in the Midst of Barriers, included five themes: Self-Regulating, Stepping into Discomfort, Cognitive Reappraising, Becoming a Change Agent, and Social Support Seeking. Findings demonstrated participants' coping efficacy and perceptions of themselves as agents of change. This study deepens the field's understanding of career development among international master's of counseling psychology students.}, } @article {pmid36628509, year = {2024}, author = {Liu, PL and Zhang, L and Ma, X and Zhao, X}, title = {Communication Matters: The Role of Patient-Centered Communication in Improving Old Adults' Health Competence and Health Outcomes.}, journal = {Health communication}, volume = {39}, number = {2}, pages = {363-375}, doi = {10.1080/10410236.2023.2166209}, pmid = {36628509}, issn = {1532-7027}, mesh = {Humans ; Aged ; *Patient-Centered Care/methods ; *Communication ; Surveys and Questionnaires ; Mental Health ; Outcome Assessment, Health Care ; }, abstract = {Research has demonstrated links between patient-centered communication (PCC) and patients' health outcomes. However, little is known about the underlying processes that may mediate the relationship. This study is one of the first to examine the influence of PCC on older adults' health outcomes, as well as the mediation role of health competence, from a longitudinal perspective. With a general basis of Street et al.'s pathway model, we proposed and tested mediation pathways linking patient-centered communication to the older population's general and mental health, mediated by health competence. Data from 2011, 2017 and 2020 iterations of the Health Information National Trends Survey (HINTS) were used for this study. This study focused on older adults aged 60 and above. Results indicated that after controlling participants' age, gender, education, income and race, PCC is related to the older people's health outcomes either directly or indirectly, irrespective of time series. Specifically, health competence was found to significantly mediate the associations between PCC and the older adults' general health or mental health over the three iterations. Noteworthily, findings from this study also revealed that different dimensions of PCC might exert different influences on older patients' health competence and health outcomes.}, } @article {pmid36624234, year = {2023}, author = {Yang, H and Hong, I and Kim, YB and Cho, KC and Oh, JH}, title = {Influence of blood viscosity models and boundary conditions on the computation of hemodynamic parameters in cerebral aneurysms using computational fluid dynamics.}, journal = {Acta neurochirurgica}, volume = {165}, number = {2}, pages = {471-482}, pmid = {36624234}, issn = {0942-0940}, mesh = {Humans ; *Intracranial Aneurysm ; Blood Viscosity ; Blood Flow Velocity ; Hydrodynamics ; Models, Cardiovascular ; Hemodynamics ; Computer Simulation ; }, abstract = {BACKGROUND: Computational fluid dynamics (CFD) is widely used to calculate hemodynamic parameters that are known to influence cerebral aneurysms. However, the boundary conditions for CFD are chosen without any specific criteria. Our objective is to establish the recommendations for setting the analysis conditions for CFD analysis of the cerebral aneurysm.

METHOD: The plug and the Womersley flow were the inlet boundary conditions, and zero and pulsatile pressures were the outlet boundary conditions. In addition, the difference in the assumption of viscosity was analyzed with respect to the flow rate. The CFD process used in our research was validated using particle image velocimetry experiment data from Tupin et al.'s work to ensure the accuracy of the simulations.

RESULTS: It was confirmed that if the entrance length was sufficiently secured, the inlet and outlet boundary conditions did not affect the CFD results. In addition, it was observed that the difference in the hemodynamic parameter between Newtonian and non-Newtonian fluid decreased as the flow rate increased. Furthermore, it was confirmed that similar tendencies were evaluated when these recommendations were utilized in the patient-specific cerebral aneurysm models.

CONCLUSIONS: These results may help conduct standardized CFD analyses regardless of the research group.}, } @article {pmid36622685, year = {2023}, author = {Mitchell, P and Lee, SCM and Yoo, PE and Morokoff, A and Sharma, RP and Williams, DL and MacIsaac, C and Howard, ME and Irving, L and Vrljic, I and Williams, C and Bush, S and Balabanski, AH and Drummond, KJ and Desmond, P and Weber, D and Denison, T and Mathers, S and O'Brien, TJ and Mocco, J and Grayden, DB and Liebeskind, DS and Opie, NL and Oxley, TJ and Campbell, BCV}, title = {Assessment of Safety of a Fully Implanted Endovascular Brain-Computer Interface for Severe Paralysis in 4 Patients: The Stentrode With Thought-Controlled Digital Switch (SWITCH) Study.}, journal = {JAMA neurology}, volume = {80}, number = {3}, pages = {270-278}, pmid = {36622685}, issn = {2168-6157}, support = {UH3 NS120191/NS/NINDS NIH HHS/United States ; }, mesh = {Aged ; Humans ; Male ; Middle Aged ; Brain ; *Brain-Computer Interfaces ; Cerebral Cortex ; Paralysis/etiology ; Prospective Studies ; }, abstract = {IMPORTANCE: Brain-computer interface (BCI) implants have previously required craniotomy to deliver penetrating or surface electrodes to the brain. Whether a minimally invasive endovascular technique to deliver recording electrodes through the jugular vein to superior sagittal sinus is safe and feasible is unknown.

OBJECTIVE: To assess the safety of an endovascular BCI and feasibility of using the system to control a computer by thought.

The Stentrode With Thought-Controlled Digital Switch (SWITCH) study, a single-center, prospective, first in-human study, evaluated 5 patients with severe bilateral upper-limb paralysis, with a follow-up of 12 months. From a referred sample, 4 patients with amyotrophic lateral sclerosis and 1 with primary lateral sclerosis met inclusion criteria and were enrolled in the study. Surgical procedures and follow-up visits were performed at the Royal Melbourne Hospital, Parkville, Australia. Training sessions were performed at patients' homes and at a university clinic. The study start date was May 27, 2019, and final follow-up was completed January 9, 2022.

INTERVENTIONS: Recording devices were delivered via catheter and connected to subcutaneous electronic units. Devices communicated wirelessly to an external device for personal computer control.

MAIN OUTCOMES AND MEASURES: The primary safety end point was device-related serious adverse events resulting in death or permanent increased disability. Secondary end points were blood vessel occlusion and device migration. Exploratory end points were signal fidelity and stability over 12 months, number of distinct commands created by neuronal activity, and use of system for digital device control.

RESULTS: Of 4 patients included in analyses, all were male, and the mean (SD) age was 61 (17) years. Patients with preserved motor cortex activity and suitable venous anatomy were implanted. Each completed 12-month follow-up with no serious adverse events and no vessel occlusion or device migration. Mean (SD) signal bandwidth was 233 (16) Hz and was stable throughout study in all 4 patients (SD range across all sessions, 7-32 Hz). At least 5 attempted movement types were decoded offline, and each patient successfully controlled a computer with the BCI.

CONCLUSIONS AND RELEVANCE: Endovascular access to the sensorimotor cortex is an alternative to placing BCI electrodes in or on the dura by open-brain surgery. These final safety and feasibility data from the first in-human SWITCH study indicate that it is possible to record neural signals from a blood vessel. The favorable safety profile could promote wider and more rapid translation of BCI to people with paralysis.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03834857.}, } @article {pmid36620634, year = {2022}, author = {Cappannoli, L and Laborante, R and Galli, M and Canonico, F and Ciliberti, G and Restivo, A and Princi, G and Arcudi, A and Sabatelli, M and De Cristofaro, R and Crea, F and D'Amario, D}, title = {Feasibility, effectiveness, and safety of edoxaban administration through percutaneous endoscopic gastrostomy: 12-months follow up of the ORIGAMI study.}, journal = {Frontiers in cardiovascular medicine}, volume = {9}, number = {}, pages = {1052053}, pmid = {36620634}, issn = {2297-055X}, abstract = {BACKGROUND AND AIMS: Edoxaban proved to be safe and effective also in fragile patients, but its administration through percutaneous endoscopic gastrostomy (PEG) has not been previously investigated. The purpose of this study was to evaluate the feasibility and the preliminary safety and efficacy profiles of edoxaban administered via PEG in patients with an indication for long-term oral anticoagulation.

METHODS: ORIGAMI was a prospective, single-arm, observational study (NCT04271293). Patients with PEG and an indication for long-term anticoagulation were prospectively enrolled. Crushed edoxaban at approved doses was administered via PEG. The primary endpoint was the composite of cardio-embolic events consisting of ischemic stroke, systemic embolism, or symptomatic deep venous thrombosis/pulmonary embolism (DVT/PE). Secondary endpoints were the number of bleeding events and edoxaban plasma concentrations at steady state. We here report the 12-month results.

RESULTS: A total of 12 patients were enrolled. The main indication for PEG implantation was amyotrophic lateral sclerosis (10/12). The primary endpoint of cardio-embolic events did not occur in any patients at 12 months. All patients were in the therapeutic range of steady-state edoxaban plasma levels. Three minor bleedings were observed, while no major bleedings occurred during the observational period. A total of five patients died. All deaths were from non-cardiovascular causes and were consistent with the natural history of the pre-existing severe disease.

CONCLUSION: Our study suggests that edoxaban administration via PEG is feasible and appears safe and effective in fragile, comorbid patients, resulting in therapeutic plasma concentrations of edoxaban.

CLINICAL TRIAL REGISTRATION: [ClinicalTrials.gov], identifier [NCT04271293].}, } @article {pmid36613058, year = {2022}, author = {Faiola, A and Kamel Boulos, MN and Bin Naeem, S and Ur-Rehman, A}, title = {Integrating Social and Family Support as a Measure of Health Outcomes: Validity Implications from the Integrated Model of Health Literacy.}, journal = {International journal of environmental research and public health}, volume = {20}, number = {1}, pages = {}, pmid = {36613058}, issn = {1660-4601}, mesh = {Adolescent ; Humans ; Young Adult ; Adult ; *Health Literacy ; Family Support ; Cross-Sectional Studies ; Reproducibility of Results ; Surveys and Questionnaires ; Psychometrics ; }, abstract = {(1) Background: Health literacy (HL) is one of the key determinants of health and healthcare outcomes. The objectives of this study are to measure and validate Sørensen et al.'s integrated model of health literacy (IMHL) in a developing country's youth population, as well as to assess the impact of family affluence and social and family support on healthcare domains. (2) Methods: A cross-sectional survey was carried out of undergraduate university students in 19 public and private sector universities in Pakistan during June-August 2022. A nine-factor measurement model was tested using confirmatory factor analysis (CFA), and structural equation modeling (SEM) based on the 56 valid items obtained from three different validated scales, such as the family affluence scale (FAS-II), the multidimensional scale of perceived social support (MSPSS), and the European Health Literacy Questionnaire (the HLS-EU-Q). (3) Results: The data were collected from 1590 participants with a mean age of 21.16 (±2.027) years. The model fit indices indicate that the model partially fitted the data: χ[2] = 4.435, df = 1448, p = 0.000, RMSEA = 0.048, TLI = 0.906, CFI = 0.912, IFI = 0.912, GFI = 0.872, NFI = 0.889, RFI = 0.882, PGFI = 0.791. The structural equation model showed acceptable goodness of fit indices, indicating a significant direct influence of social and family support on healthcare and disease prevention. (4) Conclusions: Social and family support are the most influential factors, with regard to HL dimensions, in improving healthcare, disease prevention, and health promotion in low-income settings and among non-English-speaking communities.}, } @article {pmid36607566, year = {2023}, author = {Koenig, HG}, title = {A Response to the Paal et al. Rejoinder: Religiosity and Risk of Parkinson's Disease in England and the USA.}, journal = {Journal of religion and health}, volume = {62}, number = {6}, pages = {4215-4221}, pmid = {36607566}, issn = {1573-6571}, mesh = {Humans ; *Parkinson Disease/epidemiology ; Religion ; England/epidemiology ; }, abstract = {This commentary provides a response to the rejoinder by Paal et al. (Journal of Religion and Health. https://doi.org/10.1007/s10943-022-01726-y , 2023), regarding the research of Otaiku (Journal of Religion and Health. https://doi.org/10.1007/s10943-022-01603-8 , 2022) "Religiosity and risk of Parkinson's disease in England and the USA." After providing a brief overview of Otaiku's work, the commentary then addresses each of Paal et al.'s arguments. While agreeing that more research needs to be undertaken, this commentary concludes that Otaiku's research findings are well founded, suggesting that greater religiosity may lower the risk of PD.}, } @article {pmid36606153, year = {2022}, author = {Akhtar, N and Dinishak, J and Frymiare, JL}, title = {Still Infantilizing Autism? An Update and Extension of Stevenson et al. (2011).}, journal = {Autism in adulthood : challenges and management}, volume = {4}, number = {3}, pages = {224-232}, pmid = {36606153}, issn = {2573-959X}, abstract = {BACKGROUND: Stevenson et al. (2011) examined photographs and language used to represent autism on chapter websites for the Autism Society of America, autism charity websites, movies, television shows, fictional books, and U.S. new stories and found that they overwhelmingly used children to represent autism.

METHODS: Using Stevenson et al.'s methods, we tested the hypothesis that, a decade on, these same sources would now include more representations of autistic adults. We statistically compared our findings with theirs.

RESULTS: On the chapter websites of the Autism Society of America and in fictional books, the hypothesis was supported in that there were more representations of adults (19%-20%) than in the original study (5%-9%), but there were still far more representations of children than of adults. In movies, television shows, and U.S. news stories, there were equal numbers of representations of autistic adults and autistic children.

CONCLUSIONS: These findings suggest a move away from infantilizing autism in some domains, but they rely on a narrow construal of "infantilizing": the underrepresentation of autistic adults in media. However, even when autistic adults are represented, they may still be infantilized in various ways. Future research will need to examine the impact of infantilizing media on both autistic and non-autistic people, and other ways in which these representations are limited (e.g., gender and race/ethnicity).}, } @article {pmid36596719, year = {2023}, author = {Caldwell, DM and Thorn, JC}, title = {Commentary/Response: Economic evidence should be routinely collected and reported for studies of intervention effectiveness in mental health. A commentary on Vartiainen et al. (2022).}, journal = {Child and adolescent mental health}, volume = {28}, number = {2}, pages = {327-329}, doi = {10.1111/camh.12635}, pmid = {36596719}, issn = {1475-357X}, mesh = {Child ; Adolescent ; Humans ; *Mental Health ; *Anxiety ; Cost-Benefit Analysis ; Anxiety Disorders/therapy ; Cost-Effectiveness Analysis ; }, abstract = {Anxiety and related disorders are increasingly widespread amongst children and adolescents. Preventing mental health disorders from developing has the potential to realise long-term benefits for children and adolescents. In their paper, 'Economic evidence of preventive interventions for anxiety disorders in children and adolescents-a systematic review', Vartiainen et al. conducted a systematic review to examine economic evidence of interventions for the primary prevention of anxiety disorders in children and adolescents, under 18 years of age. Five articles were eligible for inclusion in the review, of which two were model-based economic evaluations and three conducted alongside randomised controlled trials (RCTs). All five papers used either a cost-effectiveness analysis (CEA) or cost-utility analysis (CUA) as their main analysis. Vartiainen et al. concluded that, due to the small number of studies and relatively small sample sizes, the evidence for the cost-effectiveness of anxiety prevention interventions is weak. In this commentary, the challenges of conducting economic evaluations for prevention interventions are briefly outlined and Vartiainen et al.'s findings are discussed in the context of two further reviews of economic studies, published in 2021. The first focuses on the prevention of anxiety and depression in children and young people and the second takes a broader perspective and also includes interventions for mental health promotion. Both additional reviews note the small number of published economic evaluations, and all three reviews are united in their call for economic evaluations to be conducted alongside all future mental health prevention intervention trials.}, } @article {pmid36596311, year = {2023}, author = {Song, Y and Jung, MY and Park, S and Hasnain, M and Gruss, V}, title = {Challenges of interprofessional geriatric practice in home care settings: an integrative review.}, journal = {Home health care services quarterly}, volume = {42}, number = {2}, pages = {98-123}, doi = {10.1080/01621424.2022.2164541}, pmid = {36596311}, issn = {1545-0856}, mesh = {Humans ; Aged ; Qualitative Research ; *Interprofessional Relations ; }, abstract = {This integrative review identified challenges for interprofessional home care and provided recommendations for improving geriatric home care. A search of six databases identified 982 articles; 11 of them met the review's eligibility criteria and were included in the review. Quality appraisal of the included studies was performed using two tools (Critical Appraisal Skills Program for Qualitative Research and Mixed Methods Appraisal Tool), and their overall methodological quality was found to be satisfactory. After applying D'Amour et al.'s framework, four "challenge" themes emerged: (1) lack of sharing, (2) lack of partnership, (3) limited resources and interdependency, and (4) power issues. Recommendations included providing practical multidisciplinary training guided by a standardized model, establishing streamlined communication protocols and a communication platform reflecting the actual needs of users by involving them in its design, and asking interprofessional team members to commit to home care planning and to cultivate a collaborative culture and organizational support.}, } @article {pmid36588913, year = {2022}, author = {Sun, W and Kang, X and Zhao, N and Dong, X and Li, S and Zhang, G and Liu, G and Yang, Y and Zheng, C and Yu, G and Shuai, L and Feng, Z}, title = {Study on dysphagia from 2012 to 2021: A bibliometric analysis via CiteSpace.}, journal = {Frontiers in neurology}, volume = {13}, number = {}, pages = {1015546}, pmid = {36588913}, issn = {1664-2295}, abstract = {OBJECTIVES: This study aims to review the documents on dysphagia, summarize the research direction, analyze the research hot spots and frontiers, report the research trends, and provide new ideas for future development in the field via CiteSpace.

METHODS: We retrieved articles on dysphagia published between 2012 and 2021 from the Web of Science Core Collection database. We downloaded the entire data and utilized CiteSpace version 5.8.R3 (64-bit) to analyze the number of publications annually, cited journals, countries, institutions, authors, cited authors, cited references, and keywords. We visualized the data with a knowledge map, collaborative network analysis, cluster analysis, and strongest citation burst analysis.

RESULTS: We obtained 14,007 papers with a continually increasing trend over time. The most productive country and institute in this field were the United States (4,308) and Northwestern University (236), respectively. Dysphagia (5,062) and Laryngoscope (2,812) were the most productive journals, Elizabeth Ward had the highest number of publications (84), and Logeman et al.'s article (centrality: 0.02) was the most referenced. The most common keywords were dysphagia, management, quality of life, deglutition disorder, diagnosis, aspiration, prevalence, children, outcome, and oropharyngeal dysphagia.

CONCLUSION: This study analyzed the current literature on dysphagia via CiteSpace and identified its research hot spots and frontiers. The prevalent global trends in dysphagia research and the growing public awareness about healthcare and quality of life suggest that research on dysphagia will gain popularity with further breakthroughs.}, } @article {pmid36587208, year = {2022}, author = {Hopkins, RE and Degenhardt, L and Campbell, G and Farnbach, S and Gisev, N}, title = {"Frustrated with the whole system": a qualitative framework analysis of the issues faced by people accessing health services for chronic pain.}, journal = {BMC health services research}, volume = {22}, number = {1}, pages = {1603}, pmid = {36587208}, issn = {1472-6963}, support = {1190977//National Health and Medical Research Council/ ; 1073858//National Health and Medical Research Council/ ; n/a//National Drug and Alcohol Research Centre/ ; }, mesh = {Humans ; Female ; *Chronic Pain/therapy ; Analgesics, Opioid ; Australia ; Health Services Accessibility ; Health Services ; Qualitative Research ; }, abstract = {BACKGROUND: Chronic non-cancer pain (CNCP) is complex and often requires multimodal management comprising of both pharmacological and non-pharmacological treatments. To inform delivery of CNCP management, it is important to understand how current health services providing non-pharmacological treatments are accessed by exploring the experiences of people attempting to access services. In doing so, this study sought to explore the underlying drivers of service access barriers.

METHODS: This study explored the experiences of Australians accessing services for CNCP using semi-structured telephone interviews undertaken between 01 October 2020 and 31 March 2021. Thematic analysis was guided by Levesque et al.'s 2013 conceptual framework of access to health care, with emerging themes mapped to five dimensions of accessibility and corresponding abilities of consumers: Approachability/Ability to perceive; Acceptability/Ability to seek; Availability and Accommodation/Ability to reach; Affordability/Ability to pay; and Appropriateness/Ability to engage.

RESULTS: The 26 participants (aged 24-78 years, 22 female) reported accessing a range of services including general practitioners (GP), allied health services, and specialised pain clinics, for a variety of conditions. Three themes were mapped to accessibility dimensions (in brackets): 'GP as guide or gatekeeper' (Approachability); 'Outside of my control' (Availability and Accommodation; Affordability); and 'Services aren't always good enough' (Appropriateness). A fourth identified theme illustrated how participants responded to encountering these barriers: 'Leading my own pain management'. Participant experiences suggest problems with the translation of contemporary pain management principles into practice, including continued application of biomedical health models as opposed to the biopsychosocial model, and demonstrate systemic issues with service delivery, including a lack of benchmarking of specialised services.

CONCLUSIONS: The identified themes highlight several evidence-to-practice gaps in the delivery of health services for people with CNCP in Australia. To address these gaps, there is a need for improved clinician training, increased investment in specialised pain services, and development of clear primary care pathways for CNCP management for evidence-based multimodal pain management to be accessible and equitable.}, } @article {pmid36585471, year = {2023}, author = {Narins, PM and Llano, DA and Zupanc, GKH}, title = {Neuroethology of auditory systems: contributions in memory of Albert S. Feng.}, journal = {Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology}, volume = {209}, number = {1}, pages = {1-4}, pmid = {36585471}, issn = {1432-1351}, abstract = {Albert (Al) S. Feng (1944 - 1921) was a pioneer in the area of neuroethology of auditory systems. This special issue of the Journal of Comparative Physiology A commemorates his life and work by presenting 15 articles written by friends, students, and colleagues, many of whom have become leading experts themselves in this field. Their contributions not only provide a comprehensive overview of bioacoustics in amphibians and mammals (including bats), but also are intended to inspire a new generation of scientists to advance our understanding of brain mechanisms of acoustic perception.}, } @article {pmid36584963, year = {2023}, author = {Mendoza, J and Ghirlanda, S}, title = {Modeling relational responding with artificial neural networks.}, journal = {Behavioural processes}, volume = {205}, number = {}, pages = {104816}, doi = {10.1016/j.beproc.2022.104816}, pmid = {36584963}, issn = {1872-8308}, mesh = {Animals ; *Discrimination Learning ; *Learning ; Behavior, Animal ; Generalization, Stimulus ; Columbidae ; }, abstract = {Relational responding refers to behavior that conforms to a rule for com- paring stimuli. Lazareva et al. (2014) trained pigeons to choose either the smaller or the larger of two circles, using 1-3 pairs of circles for training and 17-19 new pairs for testing. The pigeons showed relational responding on some test pairs and systematic failures on others. We present a simple artificial neural network model that reproduces the animals' behavior well, similarly to Lazareva et al.'s (2014) statistical model based on stimulus features and stimulus relationships. We analyze how the network model gener- alizes from training to test stimuli, and show that it can reconcile contrasting ideas about relational responding from the seminal works by Köhler (1929, 1918/1938, 1924), positing that animals can learn relational rules such as "choose the larger stimulus," and Spence (1937), positing that relational re- sponding can be explained based on stimulus generalization.}, } @article {pmid36580617, year = {2023}, author = {Cornine, AE and Crawford, SL and Sullivan-Bolyai, S}, title = {Facilitators and Inhibitors of LPN-to-RN Student Transition: A Cross-Sectional National Survey.}, journal = {Nursing education perspectives}, volume = {44}, number = {1}, pages = {18-23}, pmid = {36580617}, issn = {1536-5026}, mesh = {Humans ; United States ; *Licensed Practical Nurses ; Cross-Sectional Studies ; Social Behavior ; Students ; *Education, Nursing, Baccalaureate ; }, abstract = {AIM: The aim of the study was to describe the transition conditions (facilitators and inhibitors) encountered by licensed practical nurses in registered nurse educational programs (LPN-to-RN students).

BACKGROUND: LPN-to-RN students are important because they may increase diversity and numbers of RNs. However, no prior study has examined transition experiences of LPN-to-RN students across the United States.

METHOD: A cross-sectional survey of LPN-to-RN students was conducted using Meleis et al.'s transition theory.

RESULTS: Students (n = 873) from 131 nursing programs responded. The most common facilitators were personal motivation and believing the content taught was valuable; the most common inhibitors were juggling multiple responsibilities and personal stress levels. Several significant relationships between transition conditions and program/student characteristics were identified.

CONCLUSION: Faculty in LPN-to-RN programs can increase support for students by refining their own actions and addressing potential challenges when LPN and non-LPN nursing students share classes.}, } @article {pmid36579440, year = {2023}, author = {Levine, MP and Sadeh-Sharvit, S}, title = {Preventing eating disorders and disordered eating in genetically vulnerable, high-risk families.}, journal = {The International journal of eating disorders}, volume = {56}, number = {3}, pages = {523-534}, doi = {10.1002/eat.23887}, pmid = {36579440}, issn = {1098-108X}, mesh = {Child ; Adolescent ; Humans ; Child, Preschool ; *Feeding and Eating Disorders/genetics/prevention & control ; *Anorexia Nervosa ; Anxiety Disorders ; Anxiety ; }, abstract = {OBJECTIVE: To close the chasm between theory about families containing a parent with an eating disorders (EDs) history and lack of selective or indicated prevention programming for such families with an older child or adolescent who is, genetically, at high risk.

METHOD: A search of four major databases for January 2000 through September 2022 yielded no publications that (a) identified genetically high-risk families with offspring ages 10 through 18; (b) devised a prevention program for the family; and (c) evaluated program effects on risk/protective factors. To rectify this gap, research on three lines of family-based prevention is reviewed: (1) programs for adolescents at genetic risk for depression or anxiety; (2) the Stanford-Dresden project for adolescents at high risk for anorexia nervosa; and (3) Sadeh-Sharvit et al.'s work concerning the Parent-Based Prevention program for mothers with an EDs history and a child under age 5.

RESULTS: The significant challenges for innovative prevention programming should be addressed by experts in effective EDs, depression, and anxiety prevention, and in family-based treatment (FBT) for EDs, collaborating with people from genetically vulnerable families. Innovative programming should focus on robust risk factors for EDs, adaptive expression of non-specific risk factors (e.g., temperament), and strengthening family functioning.

DISCUSSION: The field is overdue for development of prevention programs designed for older children or adolescents who are at risk because a parent has an ED. Evidence-based prevention programs for EDs and for depression and anxiety, as well as parent-based prevention informed by FBT, provide a springboard for addressing this gap.

PUBLIC SIGNIFICANCE: The foundation of theory and research is available for stakeholders to develop prevention programming that closes the huge gap between theory and research about families that are genetically vulnerable for eating disorders versus the complete lack of prevention programming for such families that have an older child or adolescent at high risk.}, } @article {pmid36576775, year = {2022}, author = {Gao, M and Nakajima An, D and Skolnick, J}, title = {Deep learning-driven insights into super protein complexes for outer membrane protein biogenesis in bacteria.}, journal = {eLife}, volume = {11}, number = {}, pages = {}, pmid = {36576775}, issn = {2050-084X}, support = {R35 GM118039/GM/NIGMS NIH HHS/United States ; }, mesh = {*Escherichia coli Proteins/metabolism ; *Deep Learning ; Escherichia coli/metabolism ; Molecular Chaperones/metabolism ; Peptide Hydrolases/metabolism ; Membrane Proteins/metabolism ; Bacterial Outer Membrane Proteins/metabolism ; }, abstract = {To reach their final destinations, outer membrane proteins (OMPs) of gram-negative bacteria undertake an eventful journey beginning in the cytosol. Multiple molecular machines, chaperones, proteases, and other enzymes facilitate the translocation and assembly of OMPs. These helpers usually associate, often transiently, forming large protein assemblies. They are not well understood due to experimental challenges in capturing and characterizing protein-protein interactions (PPIs), especially transient ones. Using AF2Complex, we introduce a high-throughput, deep learning pipeline to identify PPIs within the Escherichia coli cell envelope and apply it to several proteins from an OMP biogenesis pathway. Among the top confident hits obtained from screening ~1500 envelope proteins, we find not only expected interactions but also unexpected ones with profound implications. Subsequently, we predict atomic structures for these protein complexes. These structures, typically of high confidence, explain experimental observations and lead to mechanistic hypotheses for how a chaperone assists a nascent, precursor OMP emerging from a translocon, how another chaperone prevents it from aggregating and docks to a β-barrel assembly port, and how a protease performs quality control. This work presents a general strategy for investigating biological pathways by using structural insights gained from deep learning-based predictions.}, } @article {pmid36568523, year = {2023}, author = {Nawaz, MZ and Nawaz, S and Guzmán, F and Plotkina, D}, title = {The aftermath of Covid-19: The rise of pandemic animosity among consumers and its scale development.}, journal = {Journal of business research}, volume = {157}, number = {}, pages = {113550}, pmid = {36568523}, issn = {0148-2963}, abstract = {Consumer animosity captures negative attitudes to foreign products and impacts willingness to buy them. Existing constructs nevertheless fail to account for an emerging dimension: pandemic animosity. This article heeds recent calls to develop a pandemic animosity measurement scale. Its purpose is to: (i) extend Klein et al.'s (1998) animosity model by adding the pandemic animosity construct, (ii) provide a measurement scale for pandemic animosity, and (iii) explain how pandemic animosity impacts consumers' willingness to buy. Study 1 analyzes qualitative data from in-depth personal interviews with NVivo to identify themes and codes. An expert panel helped reach consensus of all indicators. Study 2 filters scale items using a pilot sample. Study 3 validates a 12-item scale with a larger representative sample. The results contribute to the consumer animosity literature by confirming the existence of pandemic animosity, providing an actionable measure, and confirming its negative impact on consumers' willingness to buy.}, } @article {pmid36567996, year = {2022}, author = {Ahmadian, M and Namnabati, M and Joonbakhsh, F}, title = {Investigation of correlation between Internet addiction and parent-child relationship in girls' adolescence in the COVID-19 pandemic.}, journal = {Journal of education and health promotion}, volume = {11}, number = {}, pages = {340}, pmid = {36567996}, issn = {2277-9531}, abstract = {BACKGROUND: Today, the increasing process with the using internet is a kind of disease among adolescents, especially in the COVID-19 pandemic. The activities such as learning-educational process and online games will become one of the problems for families. This study aimed to determine the relationship between internet addiction and parent-child relationships in high school girls in Isfahan.

MATERIALS AND METHODS: This descriptive-correlational study was conducted in girls' high school in Isfahan, Iran. One hundred and sixty students and one of their parents had participated through cluster sampling method. They filled out the Young Internet Addiction Questionnaire and the Fine et al.'s Child-Parent Questionnaire (PCRS). Data were analyzed using descriptive statistical tests and Pearson correlation test. The significance level of the data was considered 0.05.

RESULTS: The mean score (standard deviation) of internet addiction was 52.15 (5.67). 62.5% of the participants were not addicted to the use of the nternet. The mean score of the parent-child relationship was 118.24 (85.35). The results of the Pearson correlation test show that there is a significant negative correlation between parent-child relationships and Internet addiction in adolescent girls (P < 0.01).

CONCLUSIONS: Therefore, in the girl high school students who have a stronger parent-child relationship, the rate of Internet dependence is lower. Due to the current situation of the COVID-19 pandemic in terms of Internet addiction and the parent-child relationship, the present study can help nurses, teachers, and educational planners to provide a suitable information for appropriate intervention.}, } @article {pmid36563574, year = {2023}, author = {Wang, LYT and Lua, JYH and Chan, CXC and Ong, RLL and Wee, CF and Woo, BFY}, title = {Health information needs and dissemination methods for individuals living with ischemic heart disease: A systematic review.}, journal = {Patient education and counseling}, volume = {108}, number = {}, pages = {107594}, doi = {10.1016/j.pec.2022.107594}, pmid = {36563574}, issn = {1873-5134}, mesh = {Humans ; *Myocardial Ischemia/therapy ; *Information Dissemination ; *Health Services Needs and Demand ; Patient Education as Topic ; }, abstract = {OBJECTIVES: This review aimed to identify the health information needs and preferred approaches to receive health information of individuals with Ischaemic Heart Disease (IHD).

METHODS: A systematic review was conducted. Relevant literature, published in English (January 2011 to October 2021), was identified across six databases. Guided by Coulter et al.'s framework for developing patient information materials, thematic analysis was performed. The findings were presented in tables and prose.

RESULTS: Fifty-nine studies were included. Eleven themes summarised the information needs of individuals with IHD. Each theme was supported with subthemes. Forty-five studies included information on preferred methods of dissemination.

CONCLUSIONS: Our review has characterised the diverse information needs of individuals living with IHD and dissemination methods for outreach to this population. Such insights inform healthcare providers in formulating patient-centred educational interventions to empower patients to undertake successful behavioural modification.

PRACTICE IMPLICATIONS: Patient education should be personalised and delivered according to individuals' risks for IHD and modifiable risk factors. The use of web-based dissemination of patient education has gained popularity among healthcare providers but sub-optimal adherence to these web-based interventions limits behavioural modification. Adding elements of in-person patient education session to complement web-based interventions may be more propitious to effecting behavioural modification.}, } @article {pmid36563264, year = {2022}, author = {Huggins, WJ and Wan, K and McClean, J and O'Brien, TE and Wiebe, N and Babbush, R}, title = {Nearly Optimal Quantum Algorithm for Estimating Multiple Expectation Values.}, journal = {Physical review letters}, volume = {129}, number = {24}, pages = {240501}, doi = {10.1103/PhysRevLett.129.240501}, pmid = {36563264}, issn = {1079-7114}, abstract = {Many quantum algorithms involve the evaluation of expectation values. Optimal strategies for estimating a single expectation value are known, requiring a number of state preparations that scales with the target error ϵ as O(1/ϵ). In this Letter, we address the task of estimating the expectation values of M different observables, each to within additive error ϵ, with the same 1/ϵ dependence. We describe an approach that leverages Gilyén et al.'s quantum gradient estimation algorithm to achieve O(sqrt[M]/ϵ) scaling up to logarithmic factors, regardless of the commutation properties of the M observables. We prove that this scaling is worst-case optimal in the high-precision regime if the state preparation is treated as a black box, even when the operators are mutually commuting. We highlight the flexibility of our approach by presenting several generalizations, including a strategy for accelerating the estimation of a collection of dynamic correlation functions.}, } @article {pmid36548059, year = {2024}, author = {Cheng, T and Lin, Y and Wu, CW}, title = {Perspectival shapes are viewpoint-dependent relational properties.}, journal = {Psychological review}, volume = {131}, number = {1}, pages = {307-310}, doi = {10.1037/rev0000404}, pmid = {36548059}, issn = {1939-1471}, support = {//Ministry of Science and Technology/ ; }, abstract = {Recently, there is a renewed debate concerning the role of perspective in vision. Morales et al. (2020) present evidence that, in the case of viewing a rotated coin, the visual system is sensitive to what has often been called "perspectival shapes." It has generated vigorous discussions, including an online symposium by Morales and Cohen, an exchange between Linton (2021) and Morales et al. (2021), and most recently, a fierce critique by Burge and Burge (2022), in which they launch various conceptual and empirical objections. Although Morales and Firestone (2022) have responded to them recently, and we are in agreement with Morales and Firestone in general, there are further problems in Burge and Burge (2022) that are worth highlighting. The main point of this comment is that what the Burge-Burge team call "viewpoint-dependent relational properties" are simply instances of what the Morales-Firestone team call "perspectival shapes"; the confusion arises from Burge and Burge's misconstrual of Morales et al.'s claims. This shows that conceptually, the two teams are in large agreement, as Morales and Firestone (2022) also point out, and the focus should be put on the empirical disagreements, which has been covered by Morales and Firestone (2022). Relatedly, we argue that Burge and Burge (2022) misinterpret Morales et al. (2020) as supporting a new entity in perception science, and that this misinterpretation is a primary source of their apparent disagreement. This is worth pointing out because such misunderstanding generates many unnecessary quarrels that hinder progress. (PsycInfo Database Record (c) 2024 APA, all rights reserved).}, } @article {pmid36520601, year = {2023}, author = {Herbella, FAM and Katayama, RC and Patti, MG and Schlottmann, F}, title = {Chagas Disease esophagopathy may help understand Type II achalasia with focal elevated pressures. Comment on: Low et al.'s Type II achalasia with focal elevated pressures: A distinct manometric and clinical subgroup.}, journal = {Neurogastroenterology and motility}, volume = {35}, number = {3}, pages = {e14516}, doi = {10.1111/nmo.14516}, pmid = {36520601}, issn = {1365-2982}, mesh = {Humans ; *Esophageal Achalasia ; Esophageal Sphincter, Lower ; *Chagas Disease ; Manometry ; Pressure ; }, } @article {pmid36520407, year = {2023}, author = {Leimbigler, B and Li, EPH and Rush, KL and Seaton, CL}, title = {Response to Buse et al.'s letter to the editor.}, journal = {Canadian journal of public health = Revue canadienne de sante publique}, volume = {114}, number = {1}, pages = {154-155}, pmid = {36520407}, issn = {1920-7476}, } @article {pmid36516596, year = {2023}, author = {Mehrali, T and Cotte, F and Wicks, P and Gilbert, S}, title = {Response to Ben-Shabat et al.'s "Assessing data gathering of chatbot based symptom checkers - A clinical vignettes study".}, journal = {International journal of medical informatics}, volume = {170}, number = {}, pages = {104961}, doi = {10.1016/j.ijmedinf.2022.104961}, pmid = {36516596}, issn = {1872-8243}, mesh = {Humans ; *Software ; *Triage ; }, } @article {pmid36515978, year = {2022}, author = {Zhang, X and Florini, F and Visone, JE and Lionardi, I and Gross, MR and Patel, V and Deitsch, KW}, title = {A coordinated transcriptional switching network mediates antigenic variation of human malaria parasites.}, journal = {eLife}, volume = {11}, number = {}, pages = {}, pmid = {36515978}, issn = {2050-084X}, support = {F31 AI164897/AI/NIAID NIH HHS/United States ; R01 AI138499/AI/NIAID NIH HHS/United States ; R01 AI161299/AI/NIAID NIH HHS/United States ; T32 GM008539/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Humans ; *Malaria, Falciparum/parasitology ; *Parasites ; Plasmodium falciparum ; Protozoan Proteins/metabolism ; Antigenic Variation/genetics ; *Malaria ; Antigens ; }, abstract = {Malaria parasites avoid immune clearance through their ability to systematically alter antigens exposed on the surface of infected red blood cells. This is accomplished by tightly regulated transcriptional control of individual members of a large, multicopy gene family called var and is the key to both the virulence and chronic nature of malaria infections. Expression of var genes is mutually exclusive and controlled epigenetically, however how large populations of parasites coordinate var gene switching to avoid premature exposure of the antigenic repertoire is unknown. Here, we provide evidence for a transcriptional network anchored by a universally conserved gene called var2csa that coordinates the switching process. We describe a structured switching bias that shifts overtime and could shape the pattern of var expression over the course of a lengthy infection. Our results provide an explanation for a previously mysterious aspect of malaria infections and shed light on how parasites possessing a relatively small repertoire of variant antigen-encoding genes can coordinate switching events to limit antigen exposure, thereby maintaining chronic infections.}, } @article {pmid36513296, year = {2023}, author = {McGeown, L and De Young, KP and Mushquash, AR}, title = {Disconnect between sympathetically-induced hunger suppression and consumption among highly restrained eaters following stress.}, journal = {Appetite}, volume = {181}, number = {}, pages = {106419}, doi = {10.1016/j.appet.2022.106419}, pmid = {36513296}, issn = {1095-8304}, mesh = {Female ; Humans ; *Feeding Behavior ; *Hunger/physiology ; Taste Perception ; Cues ; Diet, Reducing ; Energy Intake ; Eating ; }, abstract = {Despite emphasis on findings suggesting restrained eaters increase food consumption under stress, unrestrained eaters' reduction in intake is more robust. Early proposals asserted unrestrained eaters significantly reduced intake after certain threats due to the hunger-inhibiting effects of autonomic influences, presuming unrestrained eaters are more responsive to these effects and restrained eaters rely less on physiological cues for eating. However, scant empirical evidence has substantiated these claims. This study examined whether a sequence exists whereby stress elicits autonomic activation, autonomic activation impacts hunger, and hunger then impacts eating, with dietary restraint altering the hunger-intake link. It was hypothesized that sympathetic nervous system activation would be greatest when ongoing safety from stress was uncertain, sympathetic activation would be linked to reduced hunger, and lower hunger would be associated with attenuated intake. Restraint, conceptualized via Hagan et al.'s (2017) latent restraint factors, was hypothesized to reduce the association between hunger and intake. Female participants (n = 147) were randomized to a stress + certain safety, stress + uncertain safety, or control condition. Sympathetic nervous system activity was recorded prior to a bogus taste test, which quantified ad libitum consumption of highly-palatable snack foods post-stress. Only the stress + uncertain safety condition exhibited greater sympathetic nervous system activity than the control condition. A significant index of moderated serial mediation emerged for Preoccupation with Dieting and Weight-Focused Restraint in the stress + uncertain safety condition. Though sympathetic activation decreased hunger similarly regardless of dietary restraint, only less restrained individuals significantly decreased intake. More restrained individuals ate more despite experiencing lower hunger. The disconnect between hunger and intake in more restrained eaters suggests that focus on enhancing attunement to hunger may yield greater benefit than enhancing restraint. 281 words.}, } @article {pmid36512913, year = {2023}, author = {Freeston, M and Komes, J}, title = {Revisiting uncertainty as a felt sense of unsafety: The somatic error theory of intolerance of uncertainty.}, journal = {Journal of behavior therapy and experimental psychiatry}, volume = {79}, number = {}, pages = {101827}, doi = {10.1016/j.jbtep.2022.101827}, pmid = {36512913}, issn = {1873-7943}, mesh = {Humans ; Uncertainty ; *Anxiety Disorders/psychology ; *Anxiety/psychology ; }, abstract = {Intolerance of uncertainty (IU) has gained widespread interest as a construct of broad interest from both transdiagnostic and trans-situational perspectives. We have approached this article inspired by the curiosity, clinical observation, consideration of different theoretical perspectives, speculation, optimism and indeed fun that can be seen in S. J. Rachman's work. We address some of what we know about IU before considering one way of conceptualizing IU from the standpoint of a felt sense or embodied experience. In the first part, we start with Woody and Rachman's (1994) observations of people with GAD. Second, we consider some key findings from the literature. Third, we consider two important perspectives on uncertainty, namely, Brosschot et al.'s (2016, 2018) influential Generalized Unsafety Theory of Stress and uncertainty as an emotion. In the second part, backing our clinical hunch about the importance of the felt sense of uncertainty, we consider IU from the perspective of interoception and the somatic error theory of anxiety (Khalsa & Feinstein, 2018). We propose the somatic error theory of intolerance of uncertainty, which places the experience of uncertainty at the heart of our understanding of intolerance of uncertainty. This is followed by predictions, unresolved questions, and potential clinical implications. Finally, we revisit Woody and Rachman's (1994) suggestions for treatment as internalizing "a sense of safety in a range of circumstances (p. 750)" and update this from the perspective of the felt sense of uncertainty. We finish by suggesting that uncertainty can be tolerated, perhaps accepted, and even embraced.}, } @article {pmid36508714, year = {2022}, author = {Santra, G and Martin, JML}, title = {Performance of Localized-Orbital Coupled-Cluster Approaches for the Conformational Energies of Longer n-Alkane Chains.}, journal = {The journal of physical chemistry. A}, volume = {126}, number = {50}, pages = {9375-9391}, pmid = {36508714}, issn = {1520-5215}, abstract = {We report an update and enhancement of the ACONFL (conformer energies of large alkanes [J. Phys. Chem. A2022,126, 3521-3535]) dataset. For the ACONF12 (n-dodecane) subset, we report basis set limit canonical coupled-cluster with singles, doubles, and perturbative triples [i.e., CCSD(T)] reference data obtained from the MP2-F12/cc-pV{T,Q} Z-F12 extrapolation, [CCSD(F12*)-MP2-F12]/aug-cc-pVTZ-F12, and a (T) correction from conventional CCSD(T)/aug-cc-pV{D,T} Z calculations. Then, we explored the performance of a variety of single and composite localized-orbital CCSD(T) approximations, ultimately finding an affordable localized natural orbital CCSD(T) [LNO-CCSD(T)]-based post-MP2 correction that agrees to 0.006 kcal/mol mean absolute deviation with the revised canonical reference data. In tandem with canonical MP2-F12 complete basis set extrapolation, this was then used to re-evaluate the ACONF16 and ACONF20 subsets for n-hexadecane and n-icosane, respectively. Combining those with the revised canonical reference data for the dodecane conformers (i.e., ACONF12 subset), a revised ACONFL set was obtained. It was then used to assess the performance of different localized-orbital coupled-cluster approaches, such as pair natural orbital localized CCSD(T) [PNO-LCCSD(T)] as implemented in MOLPRO, DLPNO-CCSD(T0) and DLPNO-CCSD(T1) as implemented in ORCA, and LNO-CCSD(T) as implemented in MRCC, at their respective "Normal", "Tight", "vTight", and "vvTight" accuracy settings. For a given accuracy threshold and basis set, DLPNO-CCSD(T1) and DLPNO-CCSD(T0) perform comparably. With "VeryTightPNO" cutoffs, explicitly correlated DLPNO-CCSD(T1)-F12/VDZ-F12 is the best pick among all the DLPNO-based methods tested. To isolate basis set incompleteness from localized-orbital-related truncation errors (domain, LNOs), we have also compared the localized coupled-cluster approaches with canonical DF-CCSD(T)/aug-cc-pVTZ for the ACONF12 set. We found that gradually tightening the cutoffs improves the performance of LNO-CCSD(T), and using a composite scheme such as vTight + 0.50[vTight - Tight] improves things further. For DLPNO-CCSD(T1), "TightPNO" and "VeryTightPNO" offer a statistically similar accuracy, which gets slightly better when TCutPNO is extrapolated to the complete PNO space limit. Similar to Brauer et al.'s [Phys. Chem. Chem. Phys.2016,18 (31), 20905-20925] previous report for the S66x8 noncovalent interactions, the dispersion-corrected direct random phase approximation (dRPA)-based double hybrids perform remarkably well for the ACONFL set. While the revised reference data do not affect any conclusions on the less accurate methods, they may upend orderings for more accurate methods with error statistics on the same order as the difference between reference datasets.}, } @article {pmid36507799, year = {2022}, author = {Jin, Z and Li, X and Li, T and Li, Y}, title = {Graphdiyne (CnH2n-2)-Based GDY/CuI/MIL-53(Al) S-Scheme Heterojunction for Efficient Hydrogen Evolution.}, journal = {Langmuir : the ACS journal of surfaces and colloids}, volume = {38}, number = {50}, pages = {15632-15641}, doi = {10.1021/acs.langmuir.2c02334}, pmid = {36507799}, issn = {1520-5827}, abstract = {Graphdiyne (g-CnH2n-2) is a new carbon material composed of sp and sp[2] hybrid carbon atoms. Since the synthesis by Li's team, graphdiyne has been widely studied in other fields because of its excellent properties. In this paper, graphdiyne was synthesized from copper-containing materials and the composite GDY/CuI/MIL-53(Al) S-scheme heterojunction is prepared for photocatalytic cracking of water to produce hydrogen. First, GDY/CuI was prepared by organic synthesis, and then GDY/CuI was anchored on the surface of MIL-53(Al) by in situ ultrasonic stirring. After the continuous optimization of experimental conditions, the final hydrogen evolution rate is much higher than that of MIL-53(Al). This efficient photocatalytic performance can be attributed to the S-scheme heterojunction formed by the unique energy band arrangement. At the same time, the mechanism of charge transfer was demonstrated by in situ irradiation X-ray photoelectron spectroscopy. The strong interaction among the three strongly promotes the separation and transfer of photogenerated electron-hole pairs.}, } @article {pmid36507069, year = {2022}, author = {Lissaman, R and Lancaster, TM and Parker, GD and Graham, KS and Lawrence, AD and Hodgetts, CJ}, title = {Tract-specific differences in white matter microstructure between young adult APOE ε4 carriers and non-carriers: A replication and extension study.}, journal = {Neuroimage. Reports}, volume = {2}, number = {4}, pages = {None}, pmid = {36507069}, issn = {2666-9560}, support = {MR/N01233X/1/MRC_/Medical Research Council/United Kingdom ; }, abstract = {The parahippocampal cingulum bundle (PHCB) interconnects regions known to be vulnerable to early Alzheimer's disease (AD) pathology, including posteromedial cortex and medial temporal lobe. While AD-related pathology has been robustly associated with alterations in PHCB microstructure, specifically lower fractional anisotropy (FA) and higher mean diffusivity (MD), emerging evidence indicates that the reverse pattern is evident in younger adults at increased risk of AD. In one such study, Hodgetts et al. (2019) reported that healthy young adult carriers of the apolipoprotein-E (APOE) ε4 allele - the strongest common genetic risk factor for AD - showed higher FA and lower MD in the PHCB but not the inferior longitudinal fasciculus (ILF). These results are consistent with proposals claiming that heightened neural activity and intrinsic connectivity play a significant role in increasing posteromedial cortex vulnerability to amyloid-β and tau spread beyond the medial temporal lobe. Given the implications for understanding AD risk, here we sought to replicate Hodgetts et al.'s finding in a larger sample (N = 128; 40 APOE ε4 carriers, 88 APOE ε4 non-carriers) of young adults (age range = 19-33). Extending this work, we also conducted an exploratory analysis using a more advanced measure of white matter microstructure: hindrance modulated orientational anisotropy (HMOA). Contrary to the original study, we did not observe higher FA or lower MD in the PHCB of APOE ε4 carriers relative to non-carriers. Bayes factors (BFs) further revealed moderate-to-strong evidence in support of these null findings. In addition, we observed no APOE ε4-related differences in PHCB HMOA. Our findings indicate that young adult APOE ε4 carriers and non-carriers do not differ in PHCB microstructure, casting some doubt on the notion that early-life variation in PHCB tract microstructure might enhance vulnerability to amyloid-β accumulation and/or tau spread.}, } @article {pmid36505760, year = {2022}, author = {Moore, G}, title = {Virtuous organizations: Desire, consumption and human flourishing in an era of climate change.}, journal = {Frontiers in sociology}, volume = {7}, number = {}, pages = {960054}, pmid = {36505760}, issn = {2297-7775}, abstract = {The notion of virtuous organizations has an established place in the business ethics/organization studies literature. But this conceptualization drew principally on Alasdair MacIntyre's After Virtue. His more recent work Ethics in the Conflicts of Modernity, with its focus on desire, consumption and human flourishing, demands a revisiting of the original concept. The first aim of this paper, therefore, is to provide an extended theory of the notion of the virtuous organization. An obvious application of this extended theory is to the issue of climate change. In exploring this, the paper has a further aim which is to respond to Banerjee et al.'s call for more theory building that articulates post-growth possibilities at the organization level in relation to the multiple challenges which society faces in response to the changing climate. The paper begins by summarizing the current conceptual framework of the virtuous organization while recognizing critiques of MacIntyre's work and its organizational application. It then turns to the issues of desire and consumption highlighted in MacIntyre's latest book, drawing also on an extended literature in these areas including insights from Girard's work, and concluding with MacIntyre's contentions in relation to human flourishing. This leads to the extended conceptual framework which is then applied to the issue of climate change. The particular theoretical contribution of the paper is to understand virtuous organizations as playing an important role in the redirection and re-education of desires, leading to the pursuit of goods that we have good reason to desire, and so to the good for individuals and communities, and ultimately to human flourishing within ecological limits. The similarities with and differences from the degrowth/post-growth movement are explored to demonstrate the distinctive contribution a MacIntyrean approach makes. The practical implications of this theoretical contribution are then spelled out, including a consideration of the potential ubiquity or otherwise of this approach, before conclusions are drawn.}, } @article {pmid36504290, year = {2023}, author = {Eldabe, S and Gilligan, C and Taylor, RS and Patel, KV and Duarte, RV}, title = {Issues in design, conduct, and conclusions of JAMA's Hara et al.'s randomized clinical trial of spinal cord burst stimulation versus placebo stimulation on disability in patients with chronic radicular pain after lumbar spine surgery.}, journal = {Pain practice : the official journal of World Institute of Pain}, volume = {23}, number = {3}, pages = {232-233}, doi = {10.1111/papr.13186}, pmid = {36504290}, issn = {1533-2500}, mesh = {Humans ; *Chronic Pain ; *Low Back Pain/surgery ; Spinal Cord ; *Spinal Cord Stimulation ; Treatment Outcome ; Randomized Controlled Trials as Topic ; }, } @article {pmid36497720, year = {2022}, author = {Suzuki, K and Hekmatikar, AHA and Jalalian, S and Abbasi, S and Ahmadi, E and Kazemi, A and Ruhee, RT and Khoramipour, K}, title = {The Potential of Exerkines in Women's COVID-19: A New Idea for a Better and More Accurate Understanding of the Mechanisms behind Physical Exercise.}, journal = {International journal of environmental research and public health}, volume = {19}, number = {23}, pages = {}, pmid = {36497720}, issn = {1660-4601}, mesh = {Humans ; Female ; *COVID-19 ; Exercise ; Obesity ; }, abstract = {The benefits of physical exercise are well-known, but there are still many questions regarding COVID-19. Chow et al.'s 2022 study, titled Exerkines and Disease, showed that a special focus on exerkines can help to better understand the underlying mechanisms of physical exercise and disease. Exerkines are a group of promising molecules that may underlie the beneficial effects of physical exercise in diseases. The idea of exerkines is to understand the effects of physical exercise on diseases better. Exerkines have a high potential for the treatment of diseases and, considering that, there is still no study of the importance of exerkines on the most dangerous disease in the world in recent years, COVID-19. This raises the fundamental question of whether exerkines have the potential to manage COVID-19. Most of the studies focused on the general changes in physical exercise in patients with COVID-19, both during the illness and after discharge from the hospital, and did not investigate the basic differences. A unique look at the management of COVID-19 by exerkines, especially in obese and overweight women who experience high severity of COVID-19 and whose recovery period is long after discharge from the hospital, can help to understand the basic mechanisms. In this review, we explore the potential of exerkines in COVID-19 by practicing physical exercise to provide compelling practice recommendations with new insights.}, } @article {pmid36490258, year = {2022}, author = {Sumner, PJ and Meyer, D and Carruthers, SP and Amirul Islam, FM and Rossell, SL}, title = {Assessing the dimensionality of scores derived from the Revised Formal Thought Disorder Self-Report Scale in schizotypy.}, journal = {PloS one}, volume = {17}, number = {12}, pages = {e0278841}, pmid = {36490258}, issn = {1932-6203}, mesh = {Humans ; *Self Report ; Surveys and Questionnaires ; Factor Analysis, Statistical ; Psychometrics ; Reproducibility of Results ; }, abstract = {The current work explored the dimensionality and convergent validity of responses to Barrera et al.'s (2015) 29-item Formal Thought Disorder-Self Scale (FTD-SS) obtained in two non-clinical samples. Exploratory factor analyses were conducted in Sample 1 (n = 324), yielding evidence of three correlated factors, although simple structure was not achieved until nine items were removed. Support for the correlated three factors model of responses to the revised 20-item scale (FTD-SS-R) was replicated when a confirmatory factor analysis was conducted in Sample 2 (n = 610). Finally, convergent associations were found between FTD-SS-R scores and scores from other schizotypy measures across both samples, though these measures only explained half of the variance in FTD-SS-R scores. Additional research is needed to evaluate the appropriateness of the items and incremental validity of the scale in non-clinical samples.}, } @article {pmid36482368, year = {2022}, author = {Yan, Y and Zeng, B and Gao, C and Song, Y and Chen, X}, title = {Reply to: 'comments on 'effects of refractive accommodation on subfoveal choroidal thickness in silicone oil-filled eyes".}, journal = {BMC ophthalmology}, volume = {22}, number = {1}, pages = {480}, pmid = {36482368}, issn = {1471-2415}, mesh = {Humans ; *Silicone Oils/adverse effects ; }, abstract = {In this article, we answered the questions in Lei Gao et al.'s comments on the "effects of refractive accommodation on subfoveal choroidal thickness in silicone oil-filled eyes" one by one.}, } @article {pmid36478017, year = {2023}, author = {Cook, KJ and Messick, C and McAuliffe, MJ}, title = {Written reflective practice abilities of SLT students across the degree programme.}, journal = {International journal of language & communication disorders}, volume = {58}, number = {4}, pages = {994-1016}, doi = {10.1111/1460-6984.12815}, pmid = {36478017}, issn = {1460-6984}, mesh = {Humans ; Cross-Sectional Studies ; Educational Status ; *Learning ; Problem Solving ; *Students ; Language Therapy ; Speech Therapy ; }, abstract = {BACKGROUND: Written reflective practice (WRP) is a teaching tool used across speech-language therapy (SLT) clinical education programmes. The process aims to support the development of reflective skills required for the workplace (e.g., problem-solving and self-evaluation).

AIMS: This cross-sectional and repeated-measures study design investigated students' demonstration of breadth of WRP across the clinical education programme.

METHODS & PROCEDURES: The participants were 77 undergraduate SLT students in their first, second or final professional year of the clinical programme. Participants wrote critical reflections following an interaction with a client/s as part of their clinical education experiences. Formative feedback was provided after each written reflection (WR). In total four WRs per participant were coded for breadth of WRP using a modification of Plack et al.'s coding schema from 2005. This was completed for each of the four time points across the academic year for each professional year.

OUTCOMES & RESULTS: There was a statistically significant association between time (i.e., professional year of the programme) and likelihood of demonstration of breadth of reflection for the lower level reflective element of 'attend' and higher level reflective element of 're-evaluate'. A positive trend between time and likelihood of demonstration of breadth of reflection was seen for the lower level element of 'reflection-for-action'. Final-professional-year students exhibited significant enhancements in the higher level elements (e.g., 'premise') compared with first- and second-professional-year students.

This group of SLT students exhibited significant change in breadth of WRP across the degree programme. This finding has positive implications for facilitating WRP with students and using the current coding framework in clinical programmes.

WHAT THIS PAPER ADDS: What is already known on this subject WRP is one form of reflective practice (RP) used in SLT, allied health, medical and nursing clinical education programmes. Researchers have suggested that RP skills develop over time for students. Previously, studies examining WRP have focused on one off assessment of skill or over a timeframe of 6-10 weeks. Here, we examine SLT students' WRP skills across the degree programme. What this paper adds to existing knowledge SLT students exhibited significant positive change in breadth of WRP across the degree programme as their clinical experience increased. Our results provide quantitative information in support of using RP as a learning tool throughout clinical education programmes for SLT. What are the potential or actual clinical implications of this work? This study offers support for educators of SLT students; for example, how educators can assess WRP, and how educators can foster SLT student skill development with formative feedback and reflective questioning. This study also offers support for student SLT, for example, describing how WRP can be part of their individualized learning approach and provide a purposeful examination of self and clinical skill development.}, } @article {pmid36468878, year = {2023}, author = {Turner, R and Vallée-Tourangeau, F}, title = {Challenges of measuring empathic accuracy: A mentalizing versus experience-sharing paradigm.}, journal = {The British journal of social psychology}, volume = {62}, number = {2}, pages = {972-991}, doi = {10.1111/bjso.12612}, pmid = {36468878}, issn = {2044-8309}, mesh = {Humans ; *Mentalization ; Empathy ; Emotions/physiology ; Interpersonal Relations ; Cues ; }, abstract = {Empathic accuracy, the ability to accurately infer the mental states of others, is essential to successful interpersonal relationships. Perceivers can interpret targets' emotional experiences by decoding facial and voice cues (mentalizing) or by using their own feelings as referents (experience-sharing). We examined the relative efficacy of these processes via a replication and extension of Zhou et al. (Psychol Sci., 28, 2017, 482) who found experience-sharing to be more successful but undervalued. Participants estimated targets' emotional ratings in response to positive, neutral and negative images in mentalizing or experience-sharing conditions. Our analysis of absolute magnitudes of error showed similar levels of accuracy across process conditions (a non-replication of Zhou et al.); however, our exploratory analysis of directional variation across valence using raw scores revealed a pattern of conservative estimates for affective stimuli, which was accentuated in the mentalizing condition. Thus, our exploratory analysis lends conceptual support to Zhou et al.'s finding that experience-sharing represents the more successful process, and we replicated their finding that it was nevertheless undervalued. Extending Zhou et al., we also found that empathic accuracy was predicted by individual differences in fiction-exposure. Future research may further examine the impact of individual differences and stimulus properties in the employment of empathic inferencing strategies.}, } @article {pmid36458870, year = {2023}, author = {Gerber, BL}, title = {Wideband cardiac magnetic resonance for myocardial tissue characterization in patients with implantable cardioverter defibrillators (ICDs): comment on Patel et al.'s Impact of wideband cardiac magnetic resonance on diagnosis, decision-making, and outcomes in patients with ICD.}, journal = {European heart journal. Cardiovascular Imaging}, volume = {24}, number = {2}, pages = {190-191}, doi = {10.1093/ehjci/jeac230}, pmid = {36458870}, issn = {2047-2412}, mesh = {Humans ; *Defibrillators, Implantable ; Heart ; Myocardium/pathology ; Magnetic Resonance Imaging ; Magnetic Resonance Spectroscopy ; }, } @article {pmid36455029, year = {2023}, author = {Brasil, KM and Mims, CE and McDermott, RC and Pritchard, ME}, title = {Checking the scales: A psychometric evaluation of the Weight Concerns Scale in a sample of college-aged cisgender men from the United States.}, journal = {Psychological assessment}, volume = {35}, number = {3}, pages = {218-228}, doi = {10.1037/pas0001198}, pmid = {36455029}, issn = {1939-134X}, mesh = {Adolescent ; Humans ; Male ; Female ; United States ; Young Adult ; Psychometrics ; *Body Image ; *Anxiety ; Universities ; Anxiety Disorders ; }, abstract = {Historically, western societies have considered body image issues to predominantly affect young, White women. While in recent years men's body image issues have been increasingly highlighted by researchers and the media alike, many instruments currently used to identify clinically significant body image disturbances were developed and validated with samples solely of women and/or girls. One such measure, Killen et al.'s (1994) Weight Concerns Scale (WCS), was initially validated in a sample of adolescent girls. The WCS has yet to be validated in samples of men, despite being used in large national surveys of college men and women (e.g., the Healthy Minds Study; HMS) used to inform resources on college campuses. Accordingly, we used structural equation modeling to conduct invariance testing between college student cisgender men's (n = 2,248) and women's (n = 4,733) responses on the WCS via the HMS. Through the use of two different approaches of invariance testing, evidence for metric noninvariance of two of the five items was identified, and all five items evidenced a response pattern that favored women over men. Additionally, removing noninvariant items on the WCS impacted the moderating effect of gender with indicators of depression, anxiety, and eating disorder symptomology. These findings suggest that the use of the WCS may not be appropriate for use in a cis-male sample without modification. (PsycInfo Database Record (c) 2023 APA, all rights reserved).}, } @article {pmid36453722, year = {2022}, author = {Bearce, EA and Irons, ZH and O'Hara-Smith, JR and Kuhns, CJ and Fisher, SI and Crow, WE and Grimes, DT}, title = {Urotensin II-related peptides, Urp1 and Urp2, control zebrafish spine morphology.}, journal = {eLife}, volume = {11}, number = {}, pages = {}, pmid = {36453722}, issn = {2050-084X}, support = {F32 AR078002/AR/NIAMS NIH HHS/United States ; R35 GM142949/GM/NIGMS NIH HHS/United States ; T32 HD007348/HD/NICHD NIH HHS/United States ; R00 AR070905/AR/NIAMS NIH HHS/United States ; F31 HD105435/HD/NICHD NIH HHS/United States ; R25 HD070817/HD/NICHD NIH HHS/United States ; }, mesh = {Animals ; *Urotensins/genetics ; Zebrafish/genetics ; Spine ; *Scoliosis ; }, abstract = {The spine provides structure and support to the body, yet how it develops its characteristic morphology as the organism grows is little understood. This is underscored by the commonality of conditions in which the spine curves abnormally such as scoliosis, kyphosis, and lordosis. Understanding the origin of these spinal curves has been challenging in part due to the lack of appropriate animal models. Recently, zebrafish have emerged as promising tools with which to understand the origin of spinal curves. Using zebrafish, we demonstrate that the urotensin II-related peptides (URPs), Urp1 and Urp2, are essential for maintaining spine morphology. Urp1 and Urp2 are 10-amino acid cyclic peptides expressed by neurons lining the central canal of the spinal cord. Upon combined genetic loss of Urp1 and Urp2, adolescent-onset planar curves manifested in the caudal region of the spine. Highly similar curves were caused by mutation of Uts2r3, an URP receptor. Quantitative comparisons revealed that urotensin-associated curves were distinct from other zebrafish spinal curve mutants in curve position and direction. Last, we found that the Reissner fiber, a proteinaceous thread that sits in the central canal and has been implicated in the control of spine morphology, breaks down prior to curve formation in mutants with perturbed cilia motility but was unaffected by loss of Uts2r3. This suggests a Reissner fiber-independent mechanism of curvature in urotensin-deficient mutants. Overall, our results show that Urp1 and Urp2 control zebrafish spine morphology and establish new animal models of spine deformity.}, } @article {pmid36448259, year = {2023}, author = {Frandsen, BR}, title = {Discussion on "Instrumental variable estimation of the causal hazard ratio," by Linbo Wang, Eric Tchetgen Tchetgen, Torben Martinussen, Stijn Vansteelandt.}, journal = {Biometrics}, volume = {79}, number = {2}, pages = {551-553}, doi = {10.1111/biom.13791}, pmid = {36448259}, issn = {1541-0420}, mesh = {*Proportional Hazards Models ; Causality ; }, abstract = {Wang, et al.'s estimator for causal hazard ratios for endogenous treatments makes an important addition to a researcher's toolkit for analyzing censored duration outcomes. Their method complements existing methods in the semiparametric treatment effects literature and suggests useful avenues for future research.}, } @article {pmid36444977, year = {2022}, author = {Irgen-Gioro, S and Yoshida, S and Walling, V and Chong, S}, title = {Fixation can change the appearance of phase separation in living cells.}, journal = {eLife}, volume = {11}, number = {}, pages = {}, pmid = {36444977}, issn = {2050-084X}, mesh = {*Intrinsically Disordered Proteins/metabolism ; *Biochemical Phenomena ; }, abstract = {Fixing cells with paraformaldehyde (PFA) is an essential step in numerous biological techniques as it is thought to preserve a snapshot of biomolecular transactions in living cells. Fixed-cell imaging techniques such as immunofluorescence have been widely used to detect liquid-liquid phase separation (LLPS) in vivo. Here, we compared images, before and after fixation, of cells expressing intrinsically disordered proteins that are able to undergo LLPS. Surprisingly, we found that PFA fixation can both enhance and diminish putative LLPS behaviors. For specific proteins, fixation can even cause their droplet-like puncta to artificially appear in cells that do not have any detectable puncta in the live condition. Fixing cells in the presence of glycine, a molecule that modulates fixation rates, can reverse the fixation effect from enhancing to diminishing LLPS appearance. We further established a kinetic model of fixation in the context of dynamic protein-protein interactions. Simulations based on the model suggest that protein localization in fixed cells depends on an intricate balance of protein-protein interaction dynamics, the overall rate of fixation, and notably, the difference between fixation rates of different proteins. Consistent with simulations, live-cell single-molecule imaging experiments showed that a fast overall rate of fixation relative to protein-protein interaction dynamics can minimize fixation artifacts. Our work reveals that PFA fixation changes the appearance of LLPS from living cells, presents a caveat in studying LLPS using fixation-based methods, and suggests a mechanism underlying the fixation artifact.}, } @article {pmid36444646, year = {2022}, author = {Smith, TP and Mombrikotb, S and Ransome, E and Kontopoulos, DG and Pawar, S and Bell, T}, title = {Latent functional diversity may accelerate microbial community responses to temperature fluctuations.}, journal = {eLife}, volume = {11}, number = {}, pages = {}, pmid = {36444646}, issn = {2050-084X}, support = {BB/J014575/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Temperature ; *Microbiota ; Acclimatization ; Adaptation, Physiological ; Soil ; }, abstract = {How complex microbial communities respond to climatic fluctuations remains an open question. Due to their relatively short generation times and high functional diversity, microbial populations harbor great potential to respond as a community through a combination of strain-level phenotypic plasticity, adaptation, and species sorting. However, the relative importance of these mechanisms remains unclear. We conducted a laboratory experiment to investigate the degree to which bacterial communities can respond to changes in environmental temperature through a combination of phenotypic plasticity and species sorting alone. We grew replicate soil communities from a single location at six temperatures between 4°C and 50°C. We found that phylogenetically and functionally distinct communities emerge at each of these temperatures, with K-strategist taxa favored under cooler conditions and r-strategist taxa under warmer conditions. We show that this dynamic emergence of distinct communities across a wide range of temperatures (in essence, community-level adaptation) is driven by the resuscitation of latent functional diversity: the parent community harbors multiple strains pre-adapted to different temperatures that are able to 'switch on' at their preferred temperature without immigration or adaptation. Our findings suggest that microbial community function in nature is likely to respond rapidly to climatic temperature fluctuations through shifts in species composition by resuscitation of latent functional diversity.}, } @article {pmid36443581, year = {2023}, author = {Tse, CS and Chan, YL and Yap, MJ and Tsang, HC}, title = {The Chinese Lexicon Project II: A megastudy of speeded naming performance for 25,000+ traditional Chinese two-character words.}, journal = {Behavior research methods}, volume = {55}, number = {8}, pages = {4382-4402}, pmid = {36443581}, issn = {1554-3528}, mesh = {Humans ; Young Adult ; *Recognition, Psychology/physiology ; *Language ; Semantics ; Linguistics ; Reaction Time/physiology ; }, abstract = {Using a megastudy approach, (Tse et al., 2017 Behavior Research Methods, 49, 1503-1519) established a large-scale repository of lexical variables and lexical decision responses for more than 25,000 traditional Chinese two-character words. In the current study, we expand their database by collecting norms for speeded naming reaction times (RTs) and accuracy rates, and compiling more lexical variables (e.g., phonological consistency and semantic neighborhood size). Following Tse et al.'s procedure, about 33 college-aged native Cantonese speakers in Hong Kong read aloud each word. We conducted item-level regression analyses to test the relative predictive power of orthographic variables (e.g., stroke count), phonological variables (e.g., phonological consistency), and semantic variables (e.g., semantic transparency) in naming performance. We also compared the effects of lexical variables on naming performance and Tse et al.'s lexical decision performance to examine the extent to which effects are task-specific or task-general. Freely accessible to the research community, this resource provides a valuable addition to other influential mega-databases, such as the English Lexicon Project (Balota et al., 2004 Journal of Experimental Psychology: General, 133, 283-316), and furthers our understanding of Chinese word recognition processes.}, } @article {pmid36441423, year = {2023}, author = {Burgess, E and Lien, MC}, title = {The role of perceptual difficulty in visual hindsight bias for emotional faces.}, journal = {Psychonomic bulletin & review}, volume = {30}, number = {3}, pages = {953-962}, pmid = {36441423}, issn = {1531-5320}, mesh = {Humans ; *Emotions ; *Anger ; Happiness ; Bias ; Facial Expression ; }, abstract = {Visual hindsight bias, also known as the "saw-it-all-along" effect, is the tendency to overestimate one's perceptual abilities with the aid of outcome knowledge. Recently, Giroux et al. (2022, Emotion, https://doi.org/10.1037/emo0001068) reported robust visual hindsight bias for emotional faces except for happy. We examined whether the difficulty of emotional processing could explain their finding. As in Giroux et al., participants saw a blurred image of an emotional face (happy, angry, or neutral) that progressed to clear and were instructed to stop the clearing process when they were able to identify the emotion (foresight trials). They then were shown the clearest image of each face and determined the emotion, followed by a memory task where they were asked to adjust the blur levels to indicate the point at which they had identified the emotion earlier (hindsight trials). Experiment 1 replicated Giroux et al.'s finding, showing that participants stopped the image at a higher degree of blur during the hindsight trials than they had during the foresight trials (i.e., a visual hindsight bias) for the angry and neutral faces but not happy faces. Experiment 2 manipulated the perceptual difficulty of angry and happy faces. While the easy faces replicated the results of Experiment 1, both angry and happy faces produced strong bias when made difficult. A multinomial processing tree model suggests that visual hindsight bias for emotional faces, while robust, is sensitive to perceptual processing difficulties across emotions.}, } @article {pmid36434594, year = {2022}, author = {Zamani, M and Sigaroudi, AE and Pouralizadeh, M and Kazemnejad-Leili, E}, title = {Effect of the Digital Education Package (DEP) on prevention of anxiety in hospitalized children: a quasi-experimental study.}, journal = {BMC nursing}, volume = {21}, number = {1}, pages = {324}, pmid = {36434594}, issn = {1472-6955}, abstract = {BACKGROUND: Hospitalization of children is a stressful event. However, the child's education at the time of hospital admission can be effective for the prevention of their anxiety via the use of more attractive methods. The study's aim was to assess the effectiveness of the education using a digital education package on the level of anxiety of hospitalized children.

METHODS: This is a quasi-experimental study with the randomized block method. The sample size was calculated based on Shahrabadi et al.'s study and sixty eligible hospitalized children were allocated to the two study groups from June 2019 to December 2020, in Hefdah-e-Sahrivar hospital which is the central pediatric hospital in Rasht city. The intervention was education using a digital package that was done 15 min after the hospitalization of the children. Pediatrics' Spielberger's anxiety Inventory was used for measuring the participants' anxiety before and after the intervention. We used Chi square test, Fisher exact test and paired t-test to analyze data. A p-value < 0.05 was considered statistically significant.

RESULTS: In the post-intervention phase, total mean scores of anxiety were significantly lower in the experimental group (60.17 ± 6.46) rather than in the control group (72.6 ± 8.83) (P < 0.001). The mean anxiety scores before and after the intervention were 87.43 ± 11 vs. 60.17 ± 6.46 in the intervention group and 81.5 ± 11 vs. 72.6 ± 8.83 in the control group, respectively. There were significant differences in intergroup anxiety scores between the two study groups (P < 0.001).

CONCLUSIONS: The current study showed that the Digital Education Package (DEP) is an effective method for reducing children's anxiety during hospitalization. Therefore, we recommended it as a preferred and simple method rather than routine education for pediatric nurses.}, } @article {pmid36433388, year = {2022}, author = {Tyagi, P and Kumari, S and Alzahrani, BA and Gupta, A and Yang, MH}, title = {An Enhanced User Authentication and Key Agreement Scheme for Wireless Sensor Networks Tailored for IoT.}, journal = {Sensors (Basel, Switzerland)}, volume = {22}, number = {22}, pages = {}, pmid = {36433388}, issn = {1424-8220}, support = {FP-089-43//The Deanship of Scientific Research at King Abdulaziz University, Jeddah, Saudi Arabia/ ; Dev./1043//Research and Development Scheme/ ; MOST 111-2221-E-033 -047 -//Ministry of Science and Technology/ ; MOST 111-2218-E-A49-013-MBK -//Ministry of Science and Technology/ ; MOST 111-2218-E-002-038-//Ministry of Science and Technology/ ; }, mesh = {Humans ; Reproducibility of Results ; *Privacy ; }, abstract = {A security protocol for wireless transmission is essential to defend sensitive information from malicious enemies by providing a variety of facilities such as privacy of the user's information, secure session key, associated authentication, and user-repeal facility when a person's authorizations are suddenly disclosed. Singh et al. proposed an improved user authentication and key agreement system for wireless sensor networks (WSNs). Authors are sure that their protocol is secure from various attacks. Here, we find several security pitfalls in their scheme, such as an offline password-guessing attack, failure to protect the session key, and a man-in-the-middle attack. To remove the identified pitfalls found in Singh et al.'s scheme, we design an enhanced authentication scheme for WSNs tailored for IoT. We prove the reliability of our proposed protocol using the real or random (RoR) model. We also evaluate the proposed scheme with the associated schemes and show its superior efficacy as compared to its counterparts.}, } @article {pmid36424761, year = {2023}, author = {Battisto, D and Li, X and Dong, J and Hall, L and Blouin, J}, title = {Research Methods Used in Evidence-Based Design: An Analysis of Five Years of Research Articles From the HERD Journal.}, journal = {HERD}, volume = {16}, number = {1}, pages = {56-82}, doi = {10.1177/19375867221125940}, pmid = {36424761}, issn = {2167-5112}, mesh = {Humans ; *Research Design ; }, abstract = {OBJECTIVE: This study aims to analyze research methodologies from 157 research articles published in this journal in the last five years (2016-2020).

BACKGROUND: Health environments research is comprised of research covering many topics and from various disciplines worldwide. No systematic study exists to uncover themes in evidence-based design (EBD) research concerning the types of research published, people engaged in research, and the research methods employed. Understanding the nature of health environment research performed can help researchers, practitioners, and students situate their work within an EBD research structure.

METHODS: Case study research was used to analyze 157 articles published in the Health Environments Research & Design Journal devoted to EBD and research. Secondary data were extracted to capture research methods from health environments studies and then analyzed to identify themes. The design and outcome categories were structured around and the Center for Health Design's (CHD) Knowledge Repository with origins to Ulrich et al.'s Evidence-Based Design Framework.

RESULTS: Findings are reported on categories commonly found in empirical research articles: (i) key words, (ii) disciplines from authors, (iii) settings studied, (iv) populations studied or sampled, (v) research approach and study design, (vi) research strategies, (vii) data collection methods, (viii) data analysis procedures, (ix) design categories and variables, and (x) outcome categories and variables.

CONCLUSIONS: The analyses highlighted the research methods most frequently used in health environments research. Findings revealed several inconsistencies across articles on key words and the framing of research methodologies. Results suggest that there should be a consistent and overarching research taxonomy with a set of acceptable terms for effective literature searches.}, } @article {pmid36423726, year = {2023}, author = {Caldana, CRG and Hanai-Yoshida, VM and Paulino, TH and Baldo, DA and Freitas, NP and Aranha, N and Vila, MMDC and Balcão, VM and Oliveira Junior, JM}, title = {Evaluation of urban tree barks as bioindicators of environmental pollution using the X-ray fluorescence technique.}, journal = {Chemosphere}, volume = {312}, number = {Pt 2}, pages = {137257}, doi = {10.1016/j.chemosphere.2022.137257}, pmid = {36423726}, issn = {1879-1298}, mesh = {*Environmental Biomarkers ; Plant Bark ; Fluorescence ; Lead ; X-Rays ; Environmental Pollution ; *Pinus ; Trees ; Soil ; }, abstract = {Some chemical elements released in nature due to anthropogenic actions are harmful to living beings, and finding efficient and low-cost ways to measure their presence is a challenge. The major goal of this work was to use the barks of urban trees as bioindicators of the presence of these elements. For this purpose, tree barks of sixteen individual trees were collected, including Ipê (Bignoniaceae Family); Sibipiruna (Fabaceae Family); Pine (Pinaceae Family), in the city of Sorocaba, SP, Brazil, in three different districts. Two samples, one of Ipê and another of Sibipiruna, collected in the Mata Atlântica forest in Juquitiba, SP, Brazil, were used as control samples. They were also analyzed; six soil samples were collected in the same places as the tree barks in Sorocaba. The samples were analyzed using the Energy Dispersion X-Ray Fluorescence Spectroscopy technique. The elements studied ranged from Al to Bi. The results were submitted to univariate and multivariate statistical analysis showing that Sibipiruna presented a high concentration of the element Ca. At the same time, Ipê and Pine showed high concentrations of K. In the identified elements, the probable sources of contamination were pointed out, such as elements from the dust of braking automobiles (Al, Si, S, Ti, Fe, Cu, and Ba), elements from the paint used to paint the asphalt (Si, Ca, Cr and Pb) and elements from the tire tread wear (Al, S, Ca and Zn). From the analysis of soil samples and trees, it was found that there was high pollution by the element Pb in the specimens collected in front of the old Saturnia battery factory, located in the district of Éden in the city of Sorocaba, SP, Brazil (Coordinates: Lat 23K253141 m E; Long 23K7405583 m S).}, } @article {pmid36422205, year = {2022}, author = {Liu, Y and Zhao, H and Xu, H and Shi, W and Li, J and Li, Y and Canavese, F}, title = {To Angulate or Not to Angulate the Ulna during the Progressive Distraction Period Performed with a Monolateral External Fixator in Paediatric Patients with a Chronic Monteggia Fracture?.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {58}, number = {11}, pages = {}, pmid = {36422205}, issn = {1648-9144}, mesh = {Male ; Female ; Child ; Humans ; Child, Preschool ; *Monteggia's Fracture/surgery ; Retrospective Studies ; Ulna/surgery ; External Fixators ; Radius/surgery ; }, abstract = {Background and Objectives: The purpose of this study was to compare the clinical and radiographic evolution of chronic Monteggia fractures (CMFs) treated by ulnar osteotomy and monolateral external fixators (MEFs) with or without angulation of the ulna during the distraction period. Materials and Methods: This retrospective study evaluated 20 children (14 boys and 6 girls) with CMFs. According to the strategy of ulnar lengthening, two groups of patients were identified: patients undergoing gradual lengthening with (Group A, n = 11) or without ulna angulation (Group B, n = 9). The mean age at the time of surgery was 7.7 years old (range, 5.4−12.9). The mean time from initial trauma to surgery was 26.3 months (range, 1−96), and the mean follow-up was 24.6 months (range, 5.5−45.4). Clinical outcomes were evaluated by Kim et al.’s Elbow Performance Score, while radiographic outcomes were assessed on plain radiographs. Results: Age at surgery, sex, laterality, time between trauma and surgery, and time of follow up in the two groups of patients showed no significant differences. The radial head was successfully reduced in 9 of 9 and 10 of 11 patients in Groups B and A, respectively (p = 1.00). The mean time to achieve radial head reduction was shorter in Group B (18.1 ± 5.3 days) than in Group A (39.2 ± 18.7 days; p = 0.004). The mean angulation of the ulna at the end of treatment was significantly lower in Group B (0.6° ± 1.1°) than in Group A (25.9° ± 6.3°; p < 0.0001). The average ulnar lengthening at the end of treatment in Group B (14.1 ± 5.8 mm) was, on average, 7.7 mm less than that in Group A (21.8 ± 9.7 mm; p = 0.05). The Kim et al. Elbow Performance Score at the last follow-up visit was comparable between the two groups of patients (p = 1.00). Conclusions: A shorter time to achieve radial head reduction and less deformity of the ulna can be expected in paediatric patients with CMFs undergoing intraoperative restoration of ulnar alignment and gradual lengthening without angulation postoperatively.}, } @article {pmid36419835, year = {2022}, author = {Du, L and Qin, J and Wang, D and Zhao, Y and Xu, N and Wu, C and Yuan, J}, title = {Meta-analysis assessing the effectiveness of SGLT2i+GLP1RA combination therapy versus monotherapy on cardiovascular and cerebrovascular outcomes in diabetic patients.}, journal = {Frontiers in physiology}, volume = {13}, number = {}, pages = {1028486}, pmid = {36419835}, issn = {1664-042X}, abstract = {Relevant meta-analyses have confirmed the cardiovascular and renal benefits of sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP1RA) among patients with type 2 diabetes (T2D) and/or cardiorenal disease. However, it is not established whether the combination therapy of SGLT2i and GLP1RA will yield an additive benefit on cardiorenal endpoints. Lopez and colleagues recently did a cohort study (Lopez et al., Am. J. Cardiol., 2022, 181, 87-93) and aimed to address this issue. However, their findings are not consistent with those of previous studies. To confirm Lopez et al.'s findings (Lopez et al., Am. J. Cardiol., 2022, 181, 87-93) and address the aforementioned inconsistencies, we conducted a meta-analysis based on relevant studies. Our meta-analysis identified that SGLT2i + GLP1RA combination therapy was significantly associated with the reduced risks of cardiovascular/cerebrovascular atherosclerotic, heart failure-associated, and death outcomes compared with SGLT2i/GLP1RA monotherapy. These might support this combination therapy used for better reducing cardiovascular and death events in T2D patients, especially in those with high or very high cardiovascular risk. This is a commentary on a previous article (Lopez et al.'s study (Lopez et al., Am. J. Cardiol., 2022, 181, 87-93)) published outside of Frontiers. Therefore, we submitted this manuscript as an Opinion article, as suggested in the Author Guidelines.}, } @article {pmid36417562, year = {2023}, author = {Janse, PD and Bakker-Brehm, DT and Geurtzen, N and Scholing, A and Hutschemaekers, GJ}, title = {Therapists' self-assessment of time spent on learning activities and its relationship to treatment outcomes: A replication study.}, journal = {Journal of clinical psychology}, volume = {79}, number = {4}, pages = {1070-1081}, doi = {10.1002/jclp.23459}, pmid = {36417562}, issn = {1097-4679}, mesh = {Humans ; *Psychotherapy/methods ; *Self-Assessment ; Longitudinal Studies ; Treatment Outcome ; Learning ; }, abstract = {OBJECTIVES: This study investigated whether therapists' self-assessed time spent on learning activities was associated with treatment outcomes. The study was a replication of Chow et al.'s (2015) study, which showed that the most effective therapists spent more total time on solitary learning activities than less effective therapists. The present study sought to replicate this finding, and it explored the association between 25 specific activities of therapists and clients' treatment outcomes. Also, this study explored which learning activities therapists found most relevant for improving their performance.

METHODS: In this naturalistic longitudinal study, data from 2424 outpatients who were being treated by 40 different therapists were analyzed using multilevel analyses. Posttreatment scores on the OQ-45 (controlled for pretreatment client variables) were used to measure treatment outcome. The RAPID Practice-D was used to measure therapists' learning and other activities spent with the aim of improving their therapeutic skills.

RESULTS: The results showed that the total amount of time that therapists indicated they spent on learning activities did not predict clients' treatment outcomes. Also, no specific learning activities were related to clients' outcomes. Nevertheless, therapists indicated that they perceived several specific activities to be highly relevant for improving their skills.

CONCLUSION: The results showed that therapists' perceptions of how much time they spent on learning activities was not related to their performance. This might suggest that therapists' perceptions of their activities is inaccurate or that they attach value to the wrong activities. It also indicates the importance of not relying solely on the self-assessments of therapists to evaluate a therapist's training and its relationship with outcome.}, } @article {pmid36416717, year = {2023}, author = {McDowell, JJ and Klapes, B and Arashanapalli, S}, title = {A test of the evolutionary theory's account of punishment superimposed on single-alternative schedules.}, journal = {Journal of the experimental analysis of behavior}, volume = {119}, number = {1}, pages = {117-128}, doi = {10.1002/jeab.811}, pmid = {36416717}, issn = {1938-3711}, mesh = {Humans ; Reinforcement Schedule ; *Reinforcement, Psychology ; *Punishment ; Biological Evolution ; }, abstract = {A test of the evolutionary theory was conducted by replicating Bradshaw et al.'s (1977, 1978, 1979) experiments in which human participants worked on single-alternative variable-interval (VI) schedules of reinforcement under three punishment conditions: no punishment, superimposed VI punishment, and superimposed variable-ratio (VR) punishment. Artificial organisms (AOs) animated by the theory worked in the same environments. Four principal findings were reported for the human participants: (1) their behavior was well described by an hyperbola in all conditions, (2) the asymptote of the hyperbola under VI punishment was equal to the asymptote in the absence of punishment, but the asymptote under VR punishment was lower than the asymptote in the absence of punishment, (3) the parameter in the denominator of the hyperbola was larger under both VI and VR punishment than in the absence of punishment, and (4) response suppression under punishment was greater at lower than at higher reinforcement frequencies. These four outcomes were also observed in the behavior of the AOs working in the same environments, thereby confirming the theory's first-order predictions about the effects of punishment on single-alternative responding.}, } @article {pmid36409986, year = {2022}, author = {Abbott, KC and Ji, F}, title = {Perfect Compensation Is Sufficient to Explain Insect Outbreaks Previously Attributed to Overcompensation : (A Comment on Stieha et al., "The Effects of Plant Compensatory Regrowth and Induced Resistance on Herbivore Population Dynamics").}, journal = {The American naturalist}, volume = {200}, number = {6}, pages = {877-880}, doi = {10.1086/721761}, pmid = {36409986}, issn = {1537-5323}, mesh = {Animals ; *Herbivory ; *Insecta ; Plants ; Population Dynamics ; Disease Outbreaks ; }, abstract = {AbstractIn "The Effects of Plant Compensatory Regrowth and Induced Resistance on Herbivore Population Dynamics," which appeared in The American Naturalist in 2016, Stieha et al. argued that overcompensatory regrowth of plant tissues lost to herbivory ("overcompensation") promotes cyclic herbivore outbreaks. In contrast, they concluded that partial regrowth ("tolerance") stabilizes herbivore dynamics, preventing outbreaks. These conclusions were based on a comparison between two plant-herbivore models that differed in two properties: (1) whether biomass could ever be higher after herbivory and regrowth than before herbivory (i.e., is overcompensatory regrowth possible?) and (2) how much herbivory the plants could withstand before only being able to partially compensate for losses (for overcompensating plants, there was a threshold herbivory level above which this occurred, whereas tolerant plants always showed partial compensation). While Stieha et al. supposed that difference 1 was responsible for the increased propensity for outbreaks in their overcompensation model, we show here that, in fact, difference 2 is responsible. Thus, we conclude that Stieha et al.'s results about "overcompensating" plants apply more broadly: the risk of herbivore outbreaks is elevated whenever plants with low-enough herbivore loads can perfectly compensate or overcompensate for losses to herbivory.}, } @article {pmid36400173, year = {2023}, author = {Cohen, M and Weisman, A and Quintner, J}, title = {Response to van Rysewyk S and Moseley GL et al.'s Comments on Cohen et al. J Pain 2022; 23(8):1283-1293.}, journal = {The journal of pain}, volume = {24}, number = {1}, pages = {184-185}, doi = {10.1016/j.jpain.2022.11.003}, pmid = {36400173}, issn = {1528-8447}, } @article {pmid36398761, year = {2022}, author = {Kretchy, IA and Okoibhole, LO and Sanuade, OA and Jennings, H and Strachan, DL and Blandford, A and Agyei, F and Asante, P and Todowede, O and Kushitor, M and Adjaye-Gbewonyo, K and Arhinful, D and Baatiema, L and Dankyi, E and Grijalva-Eternod, CS and Fottrell, EF and de-Graft Aikins, A}, title = {Scoping review of community health participatory research projects in Ghana.}, journal = {Global health action}, volume = {15}, number = {1}, pages = {2122304}, pmid = {36398761}, issn = {1654-9880}, support = {MR/T029919/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Humans ; *Public Health ; *Community-Based Participatory Research ; Ghana ; Community Participation ; }, abstract = {BACKGROUND: Community health participation is an essential tool in health research and management where community members, researchers and other relevant stakeholders contribute to the decision-making processes. Though community participation processes can be complex and challenging, evidence from previous studies have reported significant value of engaging with community in community health projects.

OBJECTIVE: To identify the nature and extent of community involvement in community health participatory research (CHPR) projects in Ghana and draw lessons for participatory design of a new project on diabetes intervention in Accra called the Contextual Awareness Response and Evaluation (CARE) diabetes project.

METHODS: A scoping review of relevant publications on CHPR projects in Ghana which had a participatory component was undertaken. PubMed, PsycINFO, African Journal Online, Health Source: Nursing/Academic Edition, Humanities International Complete and Google Scholar were searched for articles published between January 1950 and October 2021. Levac et al.'s (2010) methodological framework for scoping reviews was used to select, collate and characterise the data.

RESULTS: Fifteen studies were included in this review of CHPR projects from multiple disciplines. Participants included community health workers, patients, caregivers, policymakers, community groups, service users and providers. Based on Pretty's participation typology, several themes were identified in relation to the involvement of participants in the identified studies. The highest levels of participation were found in two studies in the diagnosis, four in the development, five in the implementation and three in the evaluation phases of projects. Community participation across all studies was assessed as low overall.

CONCLUSION: This review showed that community participation is essential in the acceptability and feasibility of research projects in Ghana and highlighted community participation's role in the diagnosis, development, implementation and evaluation stages of projects. Lessons from this review will be considered in the development, implementation, and future evaluation of the CARE diabetes project.}, } @article {pmid36397799, year = {2022}, author = {Kudo, Y and Toyoda, T and Sugimoto, N and Tsutsumi, A}, title = {Reply to Kayauchi et al.'s questions regarding the mental health of Japanese male registered nurses.}, journal = {Journal of rural medicine : JRM}, volume = {17}, number = {4}, pages = {277-278}, pmid = {36397799}, issn = {1880-487X}, } @article {pmid36387421, year = {2022}, author = {Raj, P and Gupta, N}, title = {A Review of the National Family Health Survey Data in Addressing India's Maternal Health Situation.}, journal = {Public health reviews}, volume = {43}, number = {}, pages = {1604825}, pmid = {36387421}, issn = {0301-0422}, abstract = {Objective: This study aims to understand the trend of research conducted on issues of maternal health in India considering data provided in five rounds of National Family Health Survey (NFHS). Methods: Systematic review of literature has been conducted using multi-stage search and review process adapted from Page et al.'s (2021) PRISMA. Initially 14,570 studies were identified and only 134 articles meeting selection criterion were considered in this study. Results: Approximately 32% studies have focused on regional and state variation of maternal health status; while 27% dealt with utilization of maternal healthcare services; and 19% the socio-economic determinants of maternal health. While few studies have discussed the place of delivery, antenatal care and post-natal care visits, only five studies focus on issues related to women's autonomy, including their health-seeking behaviour, knowledge, attitude and practices related to maternal health. Conclusion: Non-communicable diseases and its role in maternal health still remains an unexplored domain of research on maternal health in India. Moreover, there exists geographical skewness in the number of studies conducted, focusing especially on few provinces while none on few others.}, } @article {pmid36382778, year = {2023}, author = {Bovin, MJ and Mahoney, CT and Klein, AB and Keane, TM and Marx, BP}, title = {Comparing the Prevalence of Probable DSM-IV and DSM-5 Posttraumatic Stress Disorder in a Sample of U.S. Military Veterans Using the PTSD Checklist.}, journal = {Assessment}, volume = {30}, number = {7}, pages = {2050-2057}, doi = {10.1177/10731911221133483}, pmid = {36382778}, issn = {1552-3489}, support = {T32 MH019836/MH/NIMH NIH HHS/United States ; }, mesh = {Humans ; *Stress Disorders, Post-Traumatic/diagnosis/epidemiology ; *Veterans ; Diagnostic and Statistical Manual of Mental Disorders ; Checklist ; Prevalence ; }, abstract = {Posttraumatic stress disorder (PTSD) changed substantially when Diagnostic and Statistical Manual of Mental Disorders transitioned from fourth (DSM-IV) to fifth (DSM-5) edition. Hoge et al. found that although diagnostic prevalence remained consistent across nomenclatures, diagnostic concordance was low (55%). Study goals were to examine both the generalizability of these findings and whether either diagnosis systematically excluded patients. U.S. veterans (N = 1,171) who completed the PTSD Checklist for DSM-IV (PCL-S) and DSM-5 (PCL-5) were classified as: probable PTSD on both measures; probable PTSD on PCL-S only; probable PTSD on PCL-5 only; or no PTSD on either measure. Diagnostic prevalence was equivalent. Unlike Hoge et al.'s findings, diagnostic concordance was high (91.3%). Furthermore, observed demographic and severity differences were driven by disparities between veterans in the no PTSD versus the probable PTSD groups, not diagnostic changes. Findings suggest translatability across measures and that diagnostic changes do not systematically exclude patients.}, } @article {pmid36380123, year = {2023}, author = {Aiello, F and Gallo Afflitto, G and Alessandri Bonetti, M and Ceccarelli, F and Cesareo, M and Nucci, C}, title = {Lax eyelid condition (LEC) and floppy eyelid syndrome (FES) prevalence in obstructive sleep apnea syndrome (OSA) patients: a systematic review and meta-analysis.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {261}, number = {6}, pages = {1505-1514}, pmid = {36380123}, issn = {1435-702X}, mesh = {Humans ; Prevalence ; Syndrome ; *Eyelid Diseases/diagnosis/epidemiology ; *Sleep Apnea, Obstructive/complications/diagnosis/epidemiology ; Eyelids ; }, abstract = {PURPOSE: Lax eyelid condition (LEC) and floppy eyelid syndrome (FES) represent two distinct conditions which have been associated with several ocular and systemic comorbidities. The main aim of this systematic review and meta-analysis is to explore the available literature to estimate the prevalence rate of LEC and FES in obstructive sleep apnea (OSA).

METHODS: The protocol of this systematic review and meta-analysis has been registered in PROSPERO. Four electronic databases (PubMed/MEDLINE, Google Scholar, Cochrane Library, Web of Science) were searched from inception to December 24, 2021. A random intercept logistic regression model was carried out for the analysis of overall proportions. Odds ratio and mean difference were reported as measures of the effect size in the presence of binary and continuous outcomes, respectively. The estimated numbers of LEC/FES patients in OSA were calculated by multiplying the prevalence rate determined by our random-effects model and the corresponding Benjafield et al.'s population prospect.

RESULTS: We included 11 studies comprising 1225 OSA patients of whom 431 and 153 affected by LEC and FES, respectively. Our model estimated a pooled prevalence rate for LEC and FES in OSA patients of 40.2% (95%CI: 28.6-53.1%) and of 22.4% (95%CI: 13.8-34.2%), respectively. The number of LEC/FES affected individuals among OSA patients is expected to peak up to 376 and to 210 million, respectively. OSA patients appeared to have a 3.4 (95%CI: 2.2-5.2) and a 3.0 (95%CI: 1.7-5.5) increased risk of developing LEC and FES than the healthy counterpart.

CONCLUSION: Prevalence of LEC and FES is higher in OSA-affected patients compared to controls. More studies are warranted to investigate the mechanisms leading to the development of LEC and/or FES in OSA patients, as well as the feasibility of the adoption of these clinical findings as screening tools for OSA.}, } @article {pmid36373158, year = {2023}, author = {Silva, DS}, title = {Reply to Basseal et al.'s "Key lessons from the COVID-19 public health response in Australia".}, journal = {The Lancet regional health. Western Pacific}, volume = {30}, number = {}, pages = {100629}, pmid = {36373158}, issn = {2666-6065}, } @article {pmid36369153, year = {2022}, author = {Acuña, V and Otto, A and Cavieres, A and Villalobos, H}, title = {Efficacy of Metacognitive Training in a Chilean Sample of People with Schizophrenia.}, journal = {Revista Colombiana de psiquiatria}, volume = {51}, number = {4}, pages = {301-308}, doi = {10.1016/j.rcpeng.2020.12.002}, pmid = {36369153}, issn = {2530-3120}, mesh = {Humans ; *Schizophrenia/therapy ; Delusions ; *Metacognition ; *Psychotic Disorders/therapy ; *Cognitive Behavioral Therapy/methods ; }, abstract = {INTRODUCTION: Moritz et al.'s metacognitive training (MCT), a new development of cognitive therapy, is a manualised group training programme, designed to correct cognitive biases involved in the formation and maintenance of psychotic symptoms, especially delusions. We report on the efficacy of MCT in a Chilean sample of people with schizophrenia.

METHODS: 50 outpatients from the Hospital Del Salvador in Valparaíso, Chile, were randomly assigned to the intervention group that received MCT or the control group that only received treatment as usual (TAU). Subjects were assessed at the beginning and end of the study with the Positive and Negative Syndrome Scale (PANSS), Cognitive Biases Questionnaire for Psychosis (CBQ-P) and Beck Cognitive Insight Scale (BCIS).

RESULTS: Greater statistically significant improvements were recorded in the MCT group, both in symptoms and cognitive biases and in cognitive insight, than in the control group. When comparing both groups, significant results in favor of MCT were only observed in positive symptoms.

CONCLUSIONS: The results of this study suggest MCT is superior to TAU in treating positive symptoms. It was not possible to demonstrate its superiority in improving cognitive biases and cognitive insight.}, } @article {pmid36358316, year = {2022}, author = {Karydi, C and García-Donas, JG and Tsiminikaki, K and Bonicelli, A and Moraitis, K and Kranioti, EF}, title = {Estimation of Age-at-Death Using Cortical Bone Histomorphometry of the Rib and Femur: A Validation Study on a British Population.}, journal = {Biology}, volume = {11}, number = {11}, pages = {}, pmid = {36358316}, issn = {2079-7737}, abstract = {Histomorphometry constitutes a valuable tool for age estimation. Histological interpopulation variability has been shown to affect the accuracy of age estimation techniques and therefore validation studies are required to test the accuracy of the pre-existing methodologies. The present research constitutes a validation study of widely known histological methods on the sixth rib and the femoral midshaft of a 19th century British population originating from Blackburn, England. An evaluation of the histomorphometric features of eleven ribs and five femora was performed and used to test the accuracy of selected methods. Results indicated that osteon area and circularity were the only histomorphometric variables that presented significant interpopulation variability. Cho et al.'s method for the ribs and the average value produced using Kerley and Ubelaker's method for intact osteon and percentage of lamellar bone equations for femur were considered the only reliable markers for estimating the age on the Blackburn sample. In the case of old individuals, Goliath et al.'s method provided more satisfactory results. Overall, the present study provides evidence on the applicability of the aging histomorphometric methods on a British sample and highlights the limitations of applying histomorphometric methods developed on different reference populations than the one under investigation.}, } @article {pmid36356057, year = {2023}, author = {De Houwer, J and Buabang, EK and Boddez, Y and Köster, M and Moors, A}, title = {Reasons to Remain Critical About the Literature on Habits: A Commentary on Wood et al. (2022).}, journal = {Perspectives on psychological science : a journal of the Association for Psychological Science}, volume = {18}, number = {4}, pages = {871-875}, doi = {10.1177/17456916221131508}, pmid = {36356057}, issn = {1745-6924}, mesh = {Humans ; *Wood ; *Habits ; Motivation ; Dissent and Disputes ; Goals ; }, abstract = {Wood et al. (2022) reviewed arguments in support of the idea that much of human behavior is habitual. In this commentary, we first point at ambiguities in the way Wood et al. referred to habits. This allows us to clarify the question that lies at the core of the debate on habits: To what extent is habitual behavior mediated by stimulus-response associations or by goal representations? We then argue that Wood et al. dismissed goal-directed explanations of habitual behavior too easily. Finally, we point out that Wood et al.'s reanalysis of our data is misleading in that a more fine-grained analysis supports rather than questions goal-directed accounts.}, } @article {pmid36353897, year = {2022}, author = {Brown, RL and Pain, R}, title = {No tinkering allowed: When the end goal requires a highly specific or risky, and complex action sequence, expect ritualistic scaffolding.}, journal = {The Behavioral and brain sciences}, volume = {45}, number = {}, pages = {e252}, doi = {10.1017/S0140525X22001315}, pmid = {36353897}, issn = {1469-1825}, mesh = {Humans ; *Goals ; *Motivation ; Learning ; }, abstract = {On Jagiello et al.'s cultural action framework, end-goal resolvability and causal transparency make possible the transmission of complex technologies through low-fidelity cultural learning. We offer three further features of goal-directed action sequences - specificity, riskiness, and complexity - which alter the effectiveness of low-fidelity cultural learning. Incorporating these into the cultural action framework generates further novel, testable predictions for bifocal stance theory.}, } @article {pmid36353878, year = {2022}, author = {Samore, T and Fessler, DMT}, title = {Implications of instrumental and ritual stances for traditionalism-threat responsivity relationships.}, journal = {The Behavioral and brain sciences}, volume = {45}, number = {}, pages = {e267}, doi = {10.1017/S0140525X22001406}, pmid = {36353878}, issn = {1469-1825}, mesh = {Humans ; *Ceremonial Behavior ; }, abstract = {Jagiello et al.'s bifocal stance theory provides a useful theoretical framework for attempting to understand the connection between greater adherence to traditional norms and greater sensitivity to threats in the world. Here, we examine the implications of the instrumental and ritual stances with regard to various evolutionary explanations for traditionalism-threat sensitivity linkages.}, } @article {pmid36353873, year = {2022}, author = {Nonaka, T}, title = {Activation of stance by cues, or attunement to the invariants in a populated environment?.}, journal = {The Behavioral and brain sciences}, volume = {45}, number = {}, pages = {e263}, doi = {10.1017/S0140525X22001261}, pmid = {36353873}, issn = {1469-1825}, support = {JP21KK0182//Japan Society for the Promotion of Science/ ; JP22H00988//Japan Society for the Promotion of Science/ ; }, mesh = {Humans ; *Cues ; Learning ; *Cultural Evolution ; }, abstract = {While I agree with the distinction between expedient and proper ways of action, I find Jagiello et al.'s account of "stance switching" debatable. Fundamental to theories of cultural evolution is the fact that the shared environment is indefinitely rich, in which individuals are provided with opportunities for learning to tune themselves to specific affordances that are relevant to emerging situations.}, } @article {pmid36353861, year = {2022}, author = {Veit, W and Browning, H}, title = {On the evolutionary origins of the bifocal stance.}, journal = {The Behavioral and brain sciences}, volume = {45}, number = {}, pages = {e270}, doi = {10.1017/S0140525X22001273}, pmid = {36353861}, issn = {1469-1825}, mesh = {Humans ; *Cultural Evolution ; }, abstract = {In this commentary we advance Jagiello et al.'s proposal by zooming in on the possible evolutionary origins of the "bifocal stance" that may have enabled a major transition in human cultural evolution, arguing that the evolution of the bifocal stance was driven by an explosion in cultural complexity arising from cooperative foraging, which led to a feedback loop between the ritual and instrumental stances.}, } @article {pmid36344751, year = {2023}, author = {Pepperberg, IM}, title = {Are dogs indeed susceptible to Kanizsa's triangle illusion?.}, journal = {Learning & behavior}, volume = {51}, number = {1}, pages = {5-6}, pmid = {36344751}, issn = {1543-4508}, mesh = {Animals ; Dogs ; Phylogeny ; *Form Perception ; Photic Stimulation ; *Optical Illusions ; Brain ; }, abstract = {Survival often depends on the ability of the visual system to process information accurately; thus, research demonstrating that a brain is susceptible to optical illusions is of considerable interest, particularly when the experiments involve phylogenetic comparisons. Are Lõoke et al.'s (Anim. Cogn, 25:43-51, 2022) data strong enough to allow the inclusion of dogs on the list of nonhumans that can perceive illusory Kanizsa figures?}, } @article {pmid36335159, year = {2022}, author = {Mariconda, A and Prpic, V and Mingolo, S and Sors, F and Agostini, T and Murgia, M}, title = {A systematic investigation reveals that Ishihara et al.'s (2008) STEARC effect only emerges when time is directly assessed.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {18822}, pmid = {36335159}, issn = {2045-2322}, mesh = {Humans ; Reaction Time/physiology ; *Time Perception/physiology ; Auditory Perception/physiology ; Acoustic Stimulation ; }, abstract = {The Spatial-TEmporal Association of Response Codes (STEARC) effect (Ishihara et al. in Cortex 44:454-461, 2008) is evidence that time is spatially coded along the horizontal axis. It consists in faster left-hand responses to early onset timing and faster right-hand responses to late onset timing. This effect has only been established using tasks that directly required to assess onset timing, while no studies investigated whether this association occurs automatically in the auditory modality. The current study investigated the occurrence of the STEARC effect by using a procedure similar to Ishihara and colleagues. Experiment 1 was a conceptual replication of the original study, in which participants directly discriminated the onset timing (early vs. late) of a target sound after listening to a sequence of auditory clicks. This experiment successfully replicated the STEARC effect and revealed that the onset timing is mapped categorically. In Experiments 2, 3a and 3b participants were asked to discriminate the timbre of the stimuli instead of directly assessing the onset timing. In these experiments, no STEARC effect was observed. This suggests that the auditory STEARC effect is only elicited when time is explicitly processed, thus questioning the automaticity of this phenomenon.}, } @article {pmid36319796, year = {2022}, author = {Zeng, L and Li, H and Chen, R and Yang, H and Zou, Y and Ke, C and Chen, J and Yu, J}, title = {Integration of molecular pathology with histopathology to accurately evaluate the biological behaviour of WHO grade 2 meningiomas and patient prognosis.}, journal = {Journal of neuro-oncology}, volume = {160}, number = {2}, pages = {497-504}, pmid = {36319796}, issn = {1573-7373}, mesh = {Humans ; *Meningioma/genetics/surgery ; *Meningeal Neoplasms/genetics/surgery ; Pathology, Molecular ; Retrospective Studies ; Neoplasm Recurrence, Local ; Prognosis ; World Health Organization ; Neoplasm Grading ; }, abstract = {PURPOSE: A molecular pathological grading method was tested in WHO grade 2 meningiomas to judge whether this molecular grading can more accurately evaluate meningioma biological behaviour.

METHODS: The medical records and paraffin-embedded tissues of surgically resected WHO grade 2 meningioma patients in our department from January 1, 2010, to December 31, 2020, were collected. The molecular pathological risk grading suggested by Sahm et al. was adopted and the patients were graded as low, intermediate and high risk. Progression-free survival (PFS), malignant progression-free survival (MPFS) and overall survival (OS) were analysed. Univariate and multivariate analysis were performed to determine the relationship between molecular risk grading and patient survival.

RESULTS: Of the 98 patients, 13 (13.2%) were graded as low risk, 63 patients (64.3%) were graded as intermediate risk, and 22 patients (22.4%) were graded as high risk. With increasing molecular risk grade, the rates of tumour recurrence, malignant progression and mortality increased significantly (P < 0.05). Multivariate analysis showed that molecular risk grading was negatively associated with PFS (HR 0.018, 95% CI 0.003-0.092), MPFS (HR 0.040, 95% CI 0.006-0.266) and OS (HR 0.088, 95% CI 0.016-0.472) (P < 0.01), and gross total resection (Simpson grade I-III) significantly prolonged PFS (HR 5.882, 95% CI 2.538-13.699) and OS (HR 2.611, 95% CI 1.117-7.299) (P < 0.05).

CONCLUSION: Sahm et al.'s molecular risk grading can further refine the classification of WHO grade 2 meningiomas and more accurately evaluate their biological behaviour and patient prognosis.}, } @article {pmid36317755, year = {2022}, author = {Swan, LET and McDonald, SE and Price, SK}, title = {Pathways to reproductive autonomy: Using path analysis to predict family planning outcomes in the United States.}, journal = {Health & social care in the community}, volume = {30}, number = {6}, pages = {e6487-e6499}, pmid = {36317755}, issn = {1365-2524}, mesh = {Pregnancy ; Humans ; United States ; Female ; Adult ; *Family Planning Services/methods ; *Contraception/methods ; Pregnancy, Unplanned ; Contraceptive Agents ; Ethnicity ; }, abstract = {In the United States, about half of pregnancies are unintended, and most women of reproductive age are at risk of unintended pregnancy. Research has explored predictors of contraceptive use and unintended pregnancy, but there is a lack of research regarding access to preferred contraceptive method(s) and the complex pathways from sociodemographic factors to these family planning outcomes. This study applied Levesque et al.'s (2013) healthcare access framework to investigate pathways from sociodemographic factors and indicators of access to family planning outcomes using secondary data. Data were collected at four time points via an online survey between November 2012 and June 2014. Participants were US women of reproductive age who were seeking to avoid pregnancy (N = 1036; Mage = 27.91, SD = 5.39; 6.9% Black, 13.6% Hispanic, 70.2% white, 9.4% other race/ethnicity). We conducted mediational path analysis, and results indicated that contraceptive knowledge (β = 0.116, p = 0.004), insurance coverage (β = 0.423, p < 0.001), and relational provider engagement (β = 0.265, p = 0.011) were significant predictors of access to preferred contraceptive method. Access to preferred contraceptive method directly predicted use of more effective contraception (β = 0.260, p < 0.001) and indirectly predicted decreased likelihood of experiencing unintended pregnancy via contraceptive method(s) effectiveness (β = -0.014, 95% confidence interval: -0.041, -0.005). This study identifies pathways to and through access to preferred contraceptive methods that may be important in determining family planning outcomes such as contraceptive use and unintended pregnancy. This information can be used to improve access to contraception, ultimately increasing reproductive autonomy by helping family planning outcomes align with patients' needs and priorities.}, } @article {pmid36316961, year = {2022}, author = {Yalch, MM and Gallagher, AR and Watters, KN}, title = {Thinking hierarchically about posttraumatic response: Commentary on Lehinger et al. (2022).}, journal = {Journal of traumatic stress}, volume = {35}, number = {6}, pages = {1810-1812}, pmid = {36316961}, issn = {1573-6598}, mesh = {Humans ; *Stress Disorders, Post-Traumatic/etiology ; Survivors ; *Sex Offenses ; Cognition ; *Problem Behavior ; }, abstract = {Lehinger et al.'s (2022) study on the associations between posttraumatic stress symptoms, posttraumatic cognitions, and alcohol use in sexual assault survivors extends previous research on posttraumatic response to sexual trauma. The study is useful for these purposes but it also raises other interesting questions about the nature of posttraumatic response and the structure of psychopathology more generally. In this commentary, we describe Lehinger et al.'s (2022) study and its findings and discuss their potential relevance for emerging transdiagnostic, hierarchical models of psychopathology.}, } @article {pmid36314360, year = {2022}, author = {Ipsen, JA and Pedersen, LT and Draborg, E and Bruun, IH and Abrahamsen, C and Viberg, B}, title = {Cost-Effectiveness of Physical Rehabilitation and Care of Older Home-Dwelling Persons after Hip Fracture: A Systematic Review and Narrative Synthesis.}, journal = {Journal of rehabilitation medicine}, volume = {54}, number = {}, pages = {jrm00351}, pmid = {36314360}, issn = {1651-2081}, mesh = {Humans ; Aged ; Aged, 80 and over ; Cost-Benefit Analysis ; *Hip Fractures/surgery/rehabilitation ; Geriatric Assessment ; Quality-Adjusted Life Years ; Quality of Life ; }, abstract = {OBJECTIVE: To provide a systematic review of the literature and knowledge base of cost per quality-adjusted life year of physical rehabilitation and care of older persons after hip fracture.

MATERIAL AND METHODS: A research librarian assisted in searching 9 databases (14 May to 27 May 2021), with exclusion of studies on cognitively impaired or institutionalized individuals. A stepwise selection process was conducted by 2 authors, study quality was assessed using Drummond et al.'s checklist, and comparison between different countries was assessed using Welte et al.'s checklist.

RESULTS: Three studies were included, which employed 3 different interventions initiated at 3 different postoperative time-points. One high-quality study demonstrated that comprehensive geriatric assessment was cost-effective compared with coordinated care. The other 2 studies did not find the interventions studied to be cost-effective, and both studies were deemed to be of moderate quality.

CONCLUSION: The body of evidence on the cost-effectiveness of physical rehabilitation and care after hip fracture is limited and heterogeneous, with only 1 high-quality study. Thus, stakeholders perform decision-making with a limited knowledge base of the cost-effectiveness of physical rehabilitation and care. We recommend researchers to assess cost-per-QALY.}, } @article {pmid36311640, year = {2022}, author = {Balis, LE and Grocke-Dewey, M}, title = {Built environment approaches: Extension personnel's preferences, barriers, and facilitators.}, journal = {Frontiers in public health}, volume = {10}, number = {}, pages = {960949}, pmid = {36311640}, issn = {2296-2565}, mesh = {Cross-Sectional Studies ; *Exercise ; *Motivation ; Built Environment ; }, abstract = {INTRODUCTION: Interventions that modify the built environment can increase population physical activity levels and prevent chronic disease. The national Cooperative Extension System is poised to implement built environment approaches (i.e., pedestrian/bicycle infrastructure and enhanced access to physical activity spaces), but implementation strategies (i.e., methods or techniques to move research to practice) are needed to improve uptake. Effective implementation strategies address relevant barriers and capitalize on facilitators. The purpose of this study was to understand 1) barriers and facilitators to implementing built environment approaches in two state Extension systems, 2) preferences for built environment approaches, and 3) preferences for implementation strategies.

METHODS: A cross-sectional online survey was used to understand Extension personnel's preferences for and barriers and facilitators to built environment approaches through a mixed-methods study design. This work was informed by anthropological inquiry as the overall research philosophy, and by the Health Impact Pyramid, Leeman et al.'s classification of implementation strategies, and the Consolidated Framework for Implementation Research as the theoretical frameworks. The survey was distributed to eligible Extension personnel (n = 42) in two states. Quantitative data analysis consisted of numbers/proportions and Friedman tests. Qualitative analysis was completed through a rapid deductive approach to quickly produce actionable results.

RESULTS: Fourteen respondents (33%) completed the survey. Most had not implemented physical activity interventions in their communities or had implemented only individual-level interventions, though were interested in implementing built environment approaches. Benches, playground improvements, and crosswalks were the most desired approaches, while facilitation, assessing community strengths and needs, and technical assistance were desired implementation strategies. The most common barriers were relative priority and available resources; facilitators were external policy and incentives and implementation climate.

DISCUSSION: Extension personnel are receptive to built environment approaches and engaged with community coalitions. Yet, invested parties prefer individual-level interventions, and agents perceive a lack of resources for implementation. Implementation strategies that build capacity in both the Extension system and community coalitions may address these barriers through increasing relative priority and sharing existing resources. This work is a first step toward compiling implementation strategies to address relevant barriers to built environment approaches in community settings.}, } @article {pmid36310665, year = {2022}, author = {Karimi, E and Sohrabi, Z and Aalaa, M}, title = {Change Management in Medical Contexts, especially in Medical Education: A Systematized Review.}, journal = {Journal of advances in medical education & professionalism}, volume = {10}, number = {4}, pages = {219-227}, pmid = {36310665}, issn = {2322-2220}, abstract = {INTRODUCTION: Change is a multifaceted and challenging process. Due to the growing and increasing volume of technologies and organizational processes, there is a need to adapt to these changes because adaptation to changes is essential for the organization survival. The purpose of this study was to investigate change management in medical education in order to identify and categorize the strategies, barriers, and other important issues related to change management.

METHODS: A systematized review of the related studies was carried out according to the Khan et al.'s guideline. Five bibliographic databases and search engines including Cochrane Library, Eric, PubMed, SCOPUS, and Web of Sciences were searched. The following keywords were used with a period constraint of 2017 to March 2021 to search various online data sources: change management and medical issues. Advanced search options and Boolean operator (AND) were also used to find out more relevant records.

RESULTS: Overall, 498 records were identified. After removing duplicate records and those with irrelevant titles, abstracts, or full texts, we selected 40 articles for data extraction. The Kotter model is frequently used to manage change. Also, consideration of resistance to change and having a plan for it have been important elements of change management.

CONCLUSION: In most cases, resistance to change was observed, and several ways for resolution merged. Resistance to change and coping strategies are considered as one of the most important factors that must be considered in change situations. Awareness of change management principles and utilization of available models can pave the way for management of the change.}, } @article {pmid36295061, year = {2022}, author = {Liu, CW and Cheng, SL}, title = {Reply to Crimi, C.; Cortegiani, A. Comment on "Liu et al. Application of High-Flow Nasal Cannula in COVID-19: A Narrative Review. Life 2022, 12, 1419".}, journal = {Life (Basel, Switzerland)}, volume = {12}, number = {10}, pages = {}, pmid = {36295061}, issn = {2075-1729}, abstract = {Thanks for Crimi et al.'s comment [...].}, } @article {pmid36276772, year = {2022}, author = {Barak, G and Carroll, MR and Dean, A}, title = {The Kids Are Alright: a New Generation of Educators.}, journal = {Medical science educator}, volume = {32}, number = {5}, pages = {1189-1194}, pmid = {36276772}, issn = {2156-8650}, abstract = {Generational theory states that as a result of experiencing the same life-altering, world-wide events at key developmental ages, individuals of a given generation share unique perspectives, values, and traits compared to other generations as reported by Johnson and Romanello (Nurse Educ. 30(5):212-216, 2005) and Howe and Strauss 2000. Thus, while individual variation still exists, generational theory can be used as a tool to predict individual behavior and capitalize on shared traits in the workplace or educational setting. The millennial generation, born between 1981 and 1996, has previously been negatively perceived; however, application of generational theory can allow for a reshaping of public perception. For example, there now exists ample research, both within and outside of medical education, on how to take advantage of typical traits of the millennial student to maximize their learning, such as Twenge (Med Educ. 43(5):398-405, 2009), Eckleberry-Hunt and Tucciarone (J Grad Med Educ. 3(4):458-461, 2011), and Nicholas (Int J Learn Annu Rev. 15(6):27-34, 2008). As the cohort ages, the focus has shifted to helping millennials reach their full potential as employees. However, due to intensive and lengthy training required, medicine is only now seeing the first cohort of millennials entering the workforce as faculty physicians. As such, academic medicine is seeing millennials move from the learner role into that of the teacher. Thus far, the influence of the shared generational characteristics on their success and challenges as clinician educators and educational leaders is novel and has not been explored in the literature. By overlaying generational theory on Srinivasan et al.'s (Acad Med. 86(10):1211-1220, 2011) proposed six competencies for medical educators, we predict the strengths and challenges of millennial medical educators and hypothesize on the impact this generation may have on academic medicine.}, } @article {pmid36276761, year = {2022}, author = {Aghaei, S and Shokrpour, N and Bazrafkan, L}, title = {The Relationship Between Reflectivity and Self-Regulated Learning in MA Medical Education Students of Shiraz University in 2018 and 2019.}, journal = {Medical science educator}, volume = {32}, number = {5}, pages = {1065-1072}, pmid = {36276761}, issn = {2156-8650}, abstract = {INTRODUCTION: Reflectivity is one of the fundamental methods of education. This study aimed to investigate the relationship between reflectivity and self-regulated learning in MA medical education students of Shiraz University of Medical Sciences in 2018 and 2019.

METHODS: In this descriptive study, 34 full time and virtual MA students of medical education participated, using census method. Data were collected through the Pintrich and DeGroot self-regulated learning and the Kember et al.'s reflectivity questionnaires. Descriptive and inferential statistics were used for data analysis, through SPSS.

RESULTS: The results showed that self-regulatory learning strategies in subjects with good reflectivity were significantly higher than those with poor reflectivity; also, the scores of cognitive strategies and motivational beliefs were significantly higher in the participants with good reflectivity. There was no significant relationship between reflectivity and subscales of self-regulated learning strategies and also between reflectivity and self-regulated learning strategies in the full time and virtual courses.

CONCLUSION: It was found that there was a positive and meaningful relationship between reflectivity and self-regulated learning. Therefore, it is recommended that the managers and professors in medical universities should provide training programs in this field in order for the students to benefit from the advantages of reflectivity and self-regulated learning.}, } @article {pmid36274669, year = {2022}, author = {Tabaku, M and Tomori, S and Cullufi, P and Dervishi, E and Paknia, O and Bauer, P}, title = {A novel de novo pathogenic variant in KDM3B gene at the first Albanian case of Diets-Jongmans syndrome: DIJOS.}, journal = {Molecular genetics and metabolism reports}, volume = {33}, number = {}, pages = {100927}, pmid = {36274669}, issn = {2214-4269}, abstract = {Diets-Jongmans syndrome, DIJOS, is a very recently described autosomal dominant condition, which is caused by heterozygous pathogenic variants in KDM3B gene and characterized by impaired intellectual development, short stature, as well as facial dysmorphism. We describe a new DIJOS patient harboring a heterozygous, novel, de novo and likely pathogenic variant in KDM3B gene, which is the first case reported after Diets et al.`s publication, to the best of our knowledge.}, } @article {pmid36270813, year = {2022}, author = {Quinn, RL and Lepre, CJ}, title = {C4 plant food loss probably influenced Paranthropus boisei's extinction: A reply to Patterson et al.'s commentary on Quinn and Lepre (2021).}, journal = {Journal of human evolution}, volume = {173}, number = {}, pages = {103269}, doi = {10.1016/j.jhevol.2022.103269}, pmid = {36270813}, issn = {1095-8606}, mesh = {Animals ; *Hominidae ; Fossils ; }, } @article {pmid36258921, year = {2023}, author = {Richardson, JC and Castellanos Reyes, D and Janakiraman, S and Duha, MSU}, title = {The Process of Developing a Digital Repository for Online Teaching Using Design-Based Research.}, journal = {TechTrends : for leaders in education & training}, volume = {67}, number = {2}, pages = {217-230}, pmid = {36258921}, issn = {8756-3894}, abstract = {The Purdue Repository for Online Teaching and Learning (PoRTAL) was developed as an Open Educational Resource (OER) for graduate students and faculty in higher education settings to enhance their online teaching skills and strategies. The PoRTAL team used a design-based research approach (DBR; Wang & Hannafin, Educational Technology Research and Development, 53(4), 5-23, 2005). In this study context, we used Van Tiem et al.'s (2012) model to identify problems faced by instructors who struggled with or were new to online teaching from a Human Performance Technology (HPT) standpoint. To address the identified needs, we created resources for online teaching and embedded our research within practical activities to further study our design process. Our efforts resulted in an HPT-OER Model for Designing Digital Repositories. The purpose of this paper is to share the DBR process that we used to develop an OER repository within an HPT model.}, } @article {pmid36256533, year = {2023}, author = {Jacobson López, D}, title = {Enhancing Inclusivity for LGBTQIA+ Student Survivors of Color Commentary: Creating a University Strategic Plan to Address Relationship Violence and Sexual Misconduct (RVSM): An Application of Principles-Focused Evaluation at Michigan State University.}, journal = {Violence against women}, volume = {29}, number = {1}, pages = {35-43}, doi = {10.1177/10778012221130107}, pmid = {36256533}, issn = {1552-8448}, mesh = {Female ; Humans ; Universities ; Michigan ; *Students ; *Transgender Persons ; Violence ; Survivors ; Male ; }, abstract = {Campbell and colleagues propose a robust and rigorous strategic model to address and reduce Relationship Violence and Sexual Misconduct (RVSM) at Michigan State University, which significantly advances the field of RVSM prevention and education, particularly for survivors belonging to marginalized populations. While prior efforts have addressed RVSM on college and university campuses, Campbell and colleagues' model is groundbreaking in its ability to reduce RVSM against lesbian, gay, bisexual, transgender, queer/questioning, intersex, and asexual/agender (LGBTQIA+) students of color, by its principles of intersectional and trauma-informed action. This commentary highlights the contributions of Campbell et al.'s model and provides recommendations for enhancing programming and postassault services by addressing the totality of LGBTQIA+ survivors of color's identities.}, } @article {pmid36252825, year = {2022}, author = {Román-Caballero, R and Lupiáñez, J}, title = {Suggestive but not conclusive: An independent meta-analysis on the auditory benefits of learning to play a musical instrument. Commentary on.}, journal = {Neuroscience and biobehavioral reviews}, volume = {142}, number = {}, pages = {104916}, doi = {10.1016/j.neubiorev.2022.104916}, pmid = {36252825}, issn = {1873-7528}, mesh = {Humans ; *Music ; Auditory Perception ; Learning ; }, abstract = {The literature on musical training suggests benefits of this activity on auditory skills (i.e., near transfer) and general cognitive abilities (i.e., far transfer). However, other positions have taken those results more skeptically, rather arguing that studies with positive outcomes suffer from methodological issues that impede inferences of causality. In the context of this debate, we conducted an independent meta-analysis similar to one recently published by Neves et al.'s, also showing auditory benefits of musical training. Our meta-analysis suggests that the available evidence is not sufficient to reach firm conclusions as interventions with design-quality features (randomization and active control) are still scarce. Moreover, the reviewed studies measured auditory skills with tests based on same/different judgments that rely on short-term memory, therefore being less sensitive to changes produced by musicmaking experiences. Although the evidence is not conclusive, the results are in line with those observed with other cognitively stimulating activities and suggest a positive impact of musical training on auditory skills. Thus, the available evidence does not support extreme versions of skepticism.}, } @article {pmid36250183, year = {2023}, author = {Chen, Y and Chen, J}, title = {A biometrics-based mutual authentication and key agreement protocol for TMIS using elliptic curve cryptography.}, journal = {Multimedia tools and applications}, volume = {82}, number = {11}, pages = {16009-16032}, pmid = {36250183}, issn = {1380-7501}, abstract = {Telecare Medicine Information System (TMIS) refers to a medical model that uses communication and information technology to realize multiple medical functions such as remote disease diagnosis, treatment, and health care. Because TMIS is carried out on an insecure public Internet, a large number of mutual authentication and key agreement protocols for TMIS have been proposed to protect the privacy of patients. Recently, Ostad-Sharif et al. proposed a novel anonymous authentication and key agreement scheme for TMIS. In this work, we will demonstrate that Ostad-Sharif et al.'s scheme exists the problems of strong authentication and inefficient password change, and it cannot resist the off-line password guessing attack. To overcome the weaknesses found in Ostad-Sharif et al.'s scheme, we propose a biometrics-based mutual authentication and key agreement protocol for TMIS, making full use of the advantages of one-way hash function and elliptic curve cryptosystem (ECC). The security of the proposed scheme is formally proved under the widely used random oracle model (ROM), and various known malicious attack resistances also are presented by the heuristic discussion. Compared with the existing related schemes, the computation cost and communication overhead of our scheme are reduced by 74.5% and 27.3% respectively.}, } @article {pmid36249171, year = {2022}, author = {Smith, SW and Kronfli, FR and Vollmer, TR}, title = {Commentary on Slocum et al. (2022): Additional Considerations for Evaluating Experimental Control.}, journal = {Perspectives on behavior science}, volume = {45}, number = {3}, pages = {667-679}, pmid = {36249171}, issn = {2520-8977}, abstract = {In the target article, Slocum et al. (2022) suggested that nonconcurrent multiple baseline designs can provide internal validity comparable to concurrent multiple baseline designs. We provide further support for this assertion; however, we highlight additional considerations for determining the relative strength of each design. We advocate for a more nuanced approach to evaluating design strength and less reliance on strict adherence to a specific set of rules because the details of the design only matter insofar as they help researchers convince others that the results are valid and accurate. We provide further support for Slocum et al.'s argument by emphasizing the relatively low probability that within-tier comparisons would fail to identify confounds. We also extend this logic to suggest that staggering implementation of the independent variable across tiers may be an unnecessary design feature in certain cases. In addition, we provide an argument that nonconcurrent multiple baseline designs may provide verification within baseline logic contrary to arguments made by previous researchers. Despite our general support for Slocum et al.'s assertions and our advocacy for more nuanced approaches to determining the strength of experimental designs, we urge experimenters to consider the perspectives of researchers from other fields who may favor concurrent multiple-baseline designs and suggest that using concurrent multiple-baseline designs when feasible may foster dissemination of behavior analytic research.}, } @article {pmid36244189, year = {2022}, author = {Walz, L and Brooks, JC and Shavelle, RM and Robertson, N and Harding, KE}, title = {Life expectancy in multiple sclerosis by EDSS score.}, journal = {Multiple sclerosis and related disorders}, volume = {68}, number = {}, pages = {104219}, doi = {10.1016/j.msard.2022.104219}, pmid = {36244189}, issn = {2211-0356}, support = {MR/L010305/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Humans ; Middle Aged ; Aged ; *Multiple Sclerosis/diagnosis ; *Persons with Disabilities ; Life Expectancy ; Registries ; Wales ; Disability Evaluation ; }, abstract = {The median survival time of newly-diagnosed MS patients without severe disabilities is approximately 30-35 years. The prognosis after the onset of severe disability has not been reported. Based on Harding et al.'s 2018 study of the Southeast Wales MS registry, we calculated life expectancies according to the Expanded Disability Status Scale (EDSS). Upon loss of independent ambulation (EDSS 6-6.5; mean age 51.2) life expectancy was 13.3 additional years. At EDSS 9-9.5 (mean age 70.8) life expectancy was 1.1 additional years. These figures provide an empirical basis for discussions of advanced MS care planning.}, } @article {pmid36238753, year = {2022}, author = {Doyle, J and McAleer, P and van Leeuwen, C and Smith, S and Murphy, E and Sillevis Smitt, M and Galvin, M and Jacobs, A and Tompkins, L and Sheerin, J and Dinsmore, J}, title = {The role of phone-based triage nurses in supporting older adults with multimorbidity to digitally self-manage - Findings from the ProACT proof-of-concept study.}, journal = {Digital health}, volume = {8}, number = {}, pages = {20552076221131140}, pmid = {36238753}, issn = {2055-2076}, abstract = {BACKGROUND: Achieving patient-centred care necessitates supporting individuals to have more involvement in the self-management of their care. Digital health technologies are widely recognised as a solution to empower more effective self-management. However, given the complexity of multiple chronic condition (multimorbidity) management, coupled with changes that occur as part of the normal ageing process, human support alongside digital self-management is often necessary for older people with multimorbidity (PwM) to sustain successful self-management.

METHODS: The aim of the study was to explore the role played by a clinical, nurse-led telephone triage service in responding to alerts generated by older adults using a digital health platform, ProACT, to self-manage multiple chronic conditions over a period of 1 year. Semi-structured interviews with participants with multimorbidity were carried out across four time points during the trial, while interviews and focus groups were conducted with triage nurses at the end of the trial. Thematic analysis was conducted on the resulting transcripts.

RESULTS: Themes found in the data include the work of triage nurses; the benefits of triage support; tensions such as anxiety due to patient monitoring; and the relationship between triage nurses and participants.

DISCUSSION: This work contributes to an understanding of how older adults with multimorbidity and triage nurses collaborate in multiple chronic disease self-management. Findings are discussed within the context of Hudon et al.'s patient-centred care framework and indicate that patient-centred care was achieved, with both PwM and triage participants reporting positive experiences, relationships and several benefits of the triage support alongside digital self-management.}, } @article {pmid36234242, year = {2022}, author = {El-Hadad, S and Samuel, AM and Samuel, FH and Doty, HW and Songmene, V}, title = {Effect of Bi and Ca on the Solidification Parameters of Sr-Modified Al-S-Cu (Mg) Alloys.}, journal = {Materials (Basel, Switzerland)}, volume = {15}, number = {19}, pages = {}, pmid = {36234242}, issn = {1996-1944}, abstract = {The effect of tramp elements, mainly Bi and Ca, on the thermal characteristics of Sr-modified Al-Si-Cu and Al-Si-Cu-Mg alloys has been investigated using thermal analysis, X-ray radiography, and field emission scanning electron microscopy (FESEM) techniques. The high affinity of Bi to interact with Sr results in an increase in the Al-Si eutectic temperature, and hence an increase in the size of eutectic silicon particles. In contrast, the Ca-Sr interaction seems to have no significant effect on the alloy thermal behavior. The effect of these interactions on porosity formation has been discussed. Hot zones may be formed in thin cavities, in particular, near the bottom of the mold, leading to formation of unexpected coarse porosity, mostly shrinkage type. The study also highlights the significance of other parameters on porosity formation, such as no melt degassing, SrO, Al2O3 (strings or bifilms), as well as the presence of iron-based intermetallics.}, } @article {pmid36226874, year = {2023}, author = {Vo, T and Canty, L}, title = {Global mental health experiences of single mothers: A mixed methods research synthesis.}, journal = {Journal of advanced nursing}, volume = {79}, number = {1}, pages = {68-82}, doi = {10.1111/jan.15461}, pmid = {36226874}, issn = {1365-2648}, mesh = {Female ; Humans ; *Mental Health ; *Mothers ; Ethnicity ; Australia ; Minority Groups ; Qualitative Research ; }, abstract = {AIM: The aim of this research is to synthesize findings from primary studies (quantitative and qualitative) that investigated the global mental health experiences of single mothers to provide a deeper understanding to better care and respond to the support needs of single mothers.

DESIGN: Hayvaert et al.'s mixed methods research synthesis approach.

DATA SOURCES: The search process in the following databases, CINAHL, PsycINFO, and Scopus resulted in eight high-quality studies (5 qualitative and 3 quantitative) published between June 2016 and July 2021.

REVIEW METHODS: Descriptive statistics and instrument scores were provided in summary form. Themes were analysed using Krippendorff's content analysis. A joint display was provided to reveal a complementary relationship between two different data sets.

RESULTS: A total of 348 single mothers participated. Amongst the pooled sample, women identified as: Japanese (n = 174), Israeli (n = 147), Black African (n = 18), African American (n = 9), Native American (n = 5), Burundian-Australian (n = 8), UK British (n = 12), Asian (n = 3), South Korean (n = 7), Indian (n = 2), Malaysian (n = 44), Hispanic/Latina (n = 1) and Eastern European (n = 3). Four themes were identified: (1) Learning to let go of the past, (2) It takes a whole village: Importance of social support, (3) Seeking a self-reliant life: Challenges with balancing career & childcare and (4) Finding strength within: Personal growth. Only one intervention utilizing creative group counselling was found to significantly decrease depression (p = .008), anxiety (p = .005), and stress (p = .012) whilst increasing self-compassion (p = .013).

CONCLUSION: It is important for clinicians who care for single mothers, particularly if they recently immigrated, are multiparous, and an ethnic minority to encourage engagement in peer-initiated counselling and obtain mental health care as necessary.

IMPACT: This study identified and addressed the mental health issues that single mothers face worldwide. This is also the first mixed methods research synthesis to report single mothers' ethnicity in nursing and midwifery literature. Thus, findings from this mixed methods research synthesis can help nurses worldwide build culturally-concordant programs in their respective community organizations and partners (e.g. community health centres, mother-child enrichment clubs), inform health policies, and promote safer spaces for many single mothers, particularly for those who will immigrate to the Global North (i.e. UK, US, Canada) and become an ethnic minority.}, } @article {pmid36222668, year = {2022}, author = {Daly, M}, title = {"Cinderella effects" in lethal child abuse are genuine and large: A comment on Nobes et al. (2019).}, journal = {Journal of experimental psychology. General}, volume = {151}, number = {11}, pages = {2968-2976}, doi = {10.1037/xge0001230}, pmid = {36222668}, issn = {1939-2222}, mesh = {Child ; *Child Abuse ; Child, Preschool ; Homicide ; Humans ; Infant ; }, abstract = {Nobes et al. (2019) combined novel analyses of homicide victimization of British preschool children with a critique of previous research reporting large Cinderella effects (excess risk to stepchildren) in this domain. Whereas Nobes and colleagues' empirical contribution is useful, the critique contains factual errors and misrepresentations of the literature in support of their conclusion that the magnitude of such effects has been greatly exaggerated. It has not, as I show by addressing Nobes et al.'s many misstatements and reviewing relevant literature that they ignored. Fatal baby batterings, in particular, have been found to exhibit Cinderella effects on the order of 100-fold or more in many studies in several countries, including Britain. Nobes et al.'s efforts to deny this reality are misguided. (PsycInfo Database Record (c) 2022 APA, all rights reserved).}, } @article {pmid36217435, year = {2022}, author = {Abreu, LM and Brandão, PCS and de Montigny, M and Ouimet, PA}, title = {An effective field theory treatment of the production and annihilation of magnetic monopoles and their relic abundance.}, journal = {The European physical journal. C, Particles and fields}, volume = {82}, number = {10}, pages = {880}, pmid = {36217435}, issn = {1434-6044}, abstract = {We revisit the thermal production and annihilation of magnetic monopoles and their relic abundance in order to gain a deeper physical interpretation on the monopole phenomenology predicted from the Baines et al.'s effective field theory, recently proposed in the description of monopole pair production via Drell-Yan and photon fusion processes. In this sense, we use of the vacuum cross sections for the Drell-Yan reactions derived within the mentioned framework to evaluate the cross section averaged over the thermal distribution associated to other particles that constitute the hot medium where the monopoles propagate. In the considered range of monopole mass with spin-zero and spin-half, our findings suggest that the thermally averaged cross sections for the pair production are highly suppressed, while at higher temperatures those for the annihilation of lighter pairs reach larger magnitudes. Besides, we observe that smaller temperature leads to a rate of annihilation for scalar monopoles smaller than the one for fermionic monopoles, which might be interpreted as a theoretical evidence of a more pronounced stability for spin-zero and heavier monopoles. Then we input these thermally averaged cross sections into the kinetic equation that describes the evolution of the monopole abundance via an extension of a freeze-out theory. Our results infer that heavier monopoles achieve the equilibrium at earlier stages of the expansion, and consequently at higher temperatures. In addition, larger monopole masses produce higher values of the relic abundance. Besides, the results indicate that the abundance does not behave differently for spin-zero and spin-half relic monopoles.}, } @article {pmid36214070, year = {2023}, author = {Al-Sheikh Hassan, M}, title = {Commentary on Joseph et al.'s (2022) "Transition Experiences of Indian Nurses Into Australian Mental Health System".}, journal = {Journal of transcultural nursing : official journal of the Transcultural Nursing Society}, volume = {34}, number = {1}, pages = {6-7}, pmid = {36214070}, issn = {1552-7832}, mesh = {Humans ; *Mental Health ; Australia ; *Asian People ; }, } @article {pmid36200031, year = {2022}, author = {Lu, Y and Gao, Q and Ren, X and Li, J and Yang, D and Zhang, Z and Han, J}, title = {Incidence and prevalence of 121 rare diseases in China: Current status and challenges: 2022 revision.}, journal = {Intractable & rare diseases research}, volume = {11}, number = {3}, pages = {96-104}, pmid = {36200031}, issn = {2186-3644}, abstract = {The current study updated data on the incidence and prevalence of 121 rare diseases listed in China's First List of Rare Diseases to provide rationales and references for the development and promotion of rare-disease-related policies. The National Health Commission of the People's Republic of China issued the Rare Disease Diagnosis and Treatment Guide (2019) (denoted here as China's Rare Disease Diagnosis and Treatment Guide). Then 121 diseases were registered with the national rare disease diagnosis and treatment network. The incidence/prevalence of 121 rare diseases varied from country to country. Data are available for a total of 76 rare diseases (76 of 121 rare diseases, 62.81%) in China, including data on the incidence of 23 rare diseases (19.01%) and data on the prevalence of 66 (54.55%). There are data on the incidence/prevalence of 112 rare diseases (112 of 121 rare diseases, 92.56%) at the global level, including data on the incidence of 86 rare diseases (71.07%) and data on the prevalence of 91 (75.21%). On average, the incidence of progressive muscular dystrophies, hyperphenylalaninemia, citrullinemia, and methylmalonic acidemia is over 1/10,000 in China. The prevalence of coronary artery ectasia, congenital scoliosis, retinitis pigmentosa, severe congenital neutropenia, congenital hyperinsulinemic hypoglycemia, and osteogenesis imperfecta is over 1/10,000 in China. All of these figures are beyond the cut-off of 1/10,000 according to the 2021 definition of rare diseases in China. As registration and investigation of rare diseases continues, the spectrum of rare diseases in some provinces is expanding. Diseases such as idiopathic pulmonary arterial hypertension, hepatolenticular degeneration, hemophilia, amyotrophic lateral sclerosis, idiopathic pulmonary fibrosis, and multiple sclerosis are relatively prevalent in some regions and cities of China. Registration efforts promote the correction of incidence/prevalence data, development of orphan drugs, coverage by medical insurance, and development of clinical and diagnostic pathways.}, } @article {pmid36190119, year = {2022}, author = {Johnstone, PS and Ogueta, M and Akay, O and Top, I and Syed, S and Stanewsky, R and Top, D}, title = {Real time, in vivo measurement of neuronal and peripheral clocks in Drosophila melanogaster.}, journal = {eLife}, volume = {11}, number = {}, pages = {}, pmid = {36190119}, issn = {2050-084X}, support = {FRN-178220//CIHR/Canada ; }, mesh = {Animals ; Drosophila melanogaster/physiology ; *Drosophila Proteins/genetics/metabolism ; Biological Clocks/physiology ; Circadian Rhythm/genetics ; Drosophila/physiology ; *Circadian Clocks/genetics ; }, abstract = {Circadian clocks are highly conserved transcriptional regulators that control ~24 hr oscillations in gene expression, physiological function, and behavior. Circadian clocks exist in almost every tissue and are thought to control tissue-specific gene expression and function, synchronized by the brain clock. Many disease states are associated with loss of circadian regulation. How and when circadian clocks fail during pathogenesis remains largely unknown because it is currently difficult to monitor tissue-specific clock function in intact organisms. Here, we developed a method to directly measure the transcriptional oscillation of distinct neuronal and peripheral clocks in live, intact Drosophila, which we term Locally Activatable BioLuminescence, or LABL. Using this method, we observed that specific neuronal and peripheral clocks exhibit distinct transcriptional properties. Loss of the receptor for PDF, a circadian neurotransmitter critical for the function of the brain clock, disrupts circadian locomotor activity but not all tissue-specific circadian clocks. We found that, while peripheral clocks in non-neuronal tissues were less stable after the loss of PDF signaling, they continued to oscillate. We also demonstrate that distinct clocks exhibit differences in their loss of oscillatory amplitude or their change in period, depending on their anatomical location, mutation, or fly age. Our results demonstrate that LABL is an effective tool that allows rapid, affordable, and direct real-time monitoring of individual clocks in vivo.}, } @article {pmid36185016, year = {2023}, author = {Boots, DP and Gulledge, LM and Wareham, J}, title = {Commentary on Campbell et al.'s "Creating a University Strategic Plan to Address Relationship Violence and Sexual Misconduct": Sustainability and Replicability Concerns.}, journal = {Violence against women}, volume = {29}, number = {1}, pages = {65-73}, doi = {10.1177/10778012221130102}, pmid = {36185016}, issn = {1552-8448}, mesh = {Humans ; Universities ; *Sex Offenses/prevention & control ; Students ; Sexual Behavior ; Violence ; }, abstract = {Campbell et al. provided a candid summary of a long-term strategic plan to address relationship violence and sexual misconduct (RVSM) at Michigan State University (MSU). Coming in the aftermath of a national scandal and public outcry regarding MSU's lack of response to RVSM on its campus, the authors describe a coordinated university community response to understanding the prevalence of RVSM on campus, developing policy to respond to RVSM, and reestablishing community and survivor trust. In this commentary, we explore the innovations and sustainability of MSU's strategic plan and its potential replicability at other institutions of higher learning.}, } @article {pmid36180802, year = {2023}, author = {Çelik, O and Adali, Z and Bari, B}, title = {Does ecological footprint in ECCAS and ECOWAS converge? Empirical evidence from a panel unit root test with sharp and smooth breaks.}, journal = {Environmental science and pollution research international}, volume = {30}, number = {6}, pages = {16253-16265}, pmid = {36180802}, issn = {1614-7499}, mesh = {*Developing Countries ; Africa ; *Economic Development ; Climate Change ; Carbon Dioxide/analysis ; }, abstract = {The costs due to climate change have been increasing day by day. In addition to the risk of losing our planet's natural assets due to the increasing destructiveness of climate-related natural disasters and extreme climate events, we are also faced with grave economic risks. For this reason, researchers have recently focused on environmental issues. Nevertheless, they generally have investigated developed countries and ignored developing and least developed countries such as African countries. The United Nations (2015) report highlights that African countries should be specially investigated. Hence, the paper analyzes whether the ecological footprint in the Economic Community of Central African States (ECCAS) and Economic Community of West African States (ECOWAS) converges for the period from 1961 to 2017. We employ Bahmani-Oskooee et al.'s (2014) panel unit root test with sharp and smooth breaks. The empirical findings demonstrate that the ecological footprint is stationary in ECCAS and ECOWAS. Stated in other words, the ecological footprint in these countries converges. Therefore, policymakers could implement similar policies to reduce the ecological footprint in these countries. This policy framework paves the way for an effective sustainable development.}, } @article {pmid36180110, year = {2022}, author = {Sueca-Comes, M and Rusu, EC and Grabowska, AM and Bates, DO}, title = {Looking Under the Lamppost: The Search for New Cancer Targets in the Human Kinome.}, journal = {Pharmacological reviews}, volume = {74}, number = {4}, pages = {1136-1145}, doi = {10.1124/pharmrev.121.000410}, pmid = {36180110}, issn = {1521-0081}, support = {MR/N01247X/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {AMP-Activated Protein Kinases ; *Antineoplastic Agents/pharmacology/therapeutic use ; Humans ; *Neoplasms/drug therapy ; Protein Kinase Inhibitors/pharmacology/therapeutic use ; Protein Serine-Threonine Kinases ; Proto-Oncogene Proteins B-raf ; Serine ; }, abstract = {The number of cancer drugs is increasing as new chemical entities are developed to target molecules, often protein kinases, driving cancer progression. In 2009, Fedorov et al. identified that of the protein kinases in the human kinome, most of the focus has been on a small subset. They highlighted that many poorly investigated protein kinases were cancer drivers, but there was no relationship between publications and involvement in cancer development or progression. Since 2009, there has been a doubling in the number of publications, patents, and drugs targeting the kinome. To determine whether this was an expansion in knowledge of well-studied targets-searching in the light under the lamppost-or an explosion of investigations into previously poorly investigated targets, we searched the literature for publications on each kinase, updating Federov et al.'s assessment of the druggable kinome. The proportion of papers focusing on the 50 most-studied kinases had not changed, and the makeup of those 50 had barely changed. The majority of new drugs (80%) were against the same group of 50 kinases identified as targets 10 years ago, and the proportion of studies investigating previously poorly investigated kinases (<1%) was unchanged. With three exceptions [p38 mitogenactivated protein kinase (p38a), AMP-activated protein kinase catalytic α-subunit 1,2, and B-Raf proto-oncogene (BRAF) serine/threonine kinase], >95% of publications addressing kinases still focused on a relatively small proportion (<50%) of the human kinome independently of their involvement as cancer drivers. There is, therefore, still extensive scope for discovery of therapeutics targeting different protein kinases in cancer and still a bias toward well-characterized targets over the innovative searchlight into the unknown. SIGNIFICANCE STATEMENT: This study presents evidence that drug discovery efforts in cancer are still to some extent focused on a narrow group of well-studied kinases 10 years after the identification of multiple novel cancer targets in the human kinome. This suggests that there is still room for researchers in academia, industry, and the not-for-profit sector to develop new and diverse therapies targeting kinases for cancer.}, } @article {pmid36178023, year = {2023}, author = {Caro, T and Andrews, J and Clark, M and Borgerhoff Mulder, M}, title = {Practical guide to coproduction in conservation science.}, journal = {Conservation biology : the journal of the Society for Conservation Biology}, volume = {37}, number = {1}, pages = {e14011}, doi = {10.1111/cobi.14011}, pmid = {36178023}, issn = {1523-1739}, mesh = {*Conservation of Natural Resources ; Tanzania ; Guidelines as Topic ; }, abstract = {We considered a series of conservation-related research projects on the island of Pemba, Tanzania, to reflect on the broad significance of Beier et al.'s recommendations for linking conservation science with practical conservation outcomes. The implementation of just some of their suggestions can advance a successful coproduction of actionable science by small research teams. Key elements include, first, scientists and managers working together in the field to ensure feedback in real time; second, questions jointly identified by managers and researchers to facilitate engaged collaboration; third, conducting research at multiple sites, thereby broadening managers' abilities to reach multiple stakeholders; and fourth, establishing a multidisciplinary team because most of the concerns of local managers require input from multiple disciplines.}, } @article {pmid36172780, year = {2022}, author = {Colombo, M}, title = {Nothing but a useful tool? (F)utility and the free-energy principle.}, journal = {The Behavioral and brain sciences}, volume = {45}, number = {}, pages = {e191}, doi = {10.1017/S0140525X22000346}, pmid = {36172780}, issn = {1469-1825}, abstract = {Bruineberg and collaborators distinguish three philosophical positions about the status of Markov blankets in the context of active inference modelling, namely: literalism, realism, and instrumentalism. They criticize the first two positions and suggest that instrumentalism is "less problematic but also less interesting" (sect. 6.1.2, para. 5) Here, I sketch how literalists and realists might reply to Bruineberg et al.'s criticisms, and I explain why instrumentalism is more interesting and contentious than what Bruineberg and collaborators suggest.}, } @article {pmid36172752, year = {2022}, author = {Raja, V and Baggs, E and Chemero, A and Anderson, ML}, title = {The emperor has no blanket!.}, journal = {The Behavioral and brain sciences}, volume = {45}, number = {}, pages = {e204}, doi = {10.1017/S0140525X22000243}, pmid = {36172752}, issn = {1469-1825}, abstract = {While we applaud Bruineberg et al.'s analysis of the differences between Markov blankets and Friston blankets, we think it is not carried out to its ultimate consequences. There are reasons to think that, once Friston blankets are accepted as a theoretical construct, they do not do the work proponents of free energy principle (FEP) attribute to them. The emperor is indeed naked.}, } @article {pmid36162302, year = {2022}, author = {Yeh, CH and Huang, HM and Kuo, CL and Huang, CY and Cheng, SF}, title = {Effectiveness of e-STORY App in clinical reasoning competency and self-directed learning among students in associate nursing program: A quasi experimental study.}, journal = {Nurse education in practice}, volume = {64}, number = {}, pages = {103456}, doi = {10.1016/j.nepr.2022.103456}, pmid = {36162302}, issn = {1873-5223}, mesh = {Clinical Competence ; Clinical Reasoning ; Humans ; Learning ; *Mobile Applications ; *Students, Nursing ; }, abstract = {AIM: The purpose of this study was to promote students' clinical reasoning (CR) and self-directed learning (SDL). The specific aims were: (1) to examine effectiveness of the e-STORY App in promoting nursing students' CR and SDL; and (2) to explore the relationships between levels of learning motivation and suitability of the e-STORY App.

BACKGROUND: CR and SDL are core competencies for nursing students. However, new graduates tend to be in adequately prepared in these competencies. Humanoid diagram uses diagrams to guide students in gaining a comprehensive view of the patient issues, which may promote attainment of these competencies. The Z generation students favor learning through smart devices for the feature of no time and spatial limitations. The e-STORY App was developed to overcome the setbacks of creating hard-copy drawings to promote learning effectiveness.

DESIGN: This quasi-experimental study used two-group repeated measure design with a convenience sample.

METHODS: A total of 77 students from two sections of the "Seminar for Clinical Case Studies" course participated in the study (experimental group: 39 students; control group: 38 students). Data were collected before, one week after and four weeks after the teaching intervention. The instruments used were demographic information sheet, Huang et al.'s (in press) Clinical reasoning scale and Cheng et al. (2010) Self-directed learning instrument.

RESULTS: There were no significant differences in the CR and SDL scores between the experimental and control groups one week after the intervention (p＞.05). Analyses of the delay effects four weeks after the intervention found significantly higher CR scores in the experimental group than the control group (p < .05). However, there were no significant differences in the SDL scores between groups (p＞.05). Analysis of the findings from the experimental group found that students with moderate and low learning motivation showed significantly higher CR scores on the posttest and follow-up test (p < .05).

CONCLUSIONS: Application of the e-STORY App as a supplementary teaching strategy promoted nursing students' CR ability, especially in students with moderate or low learning motivation. It is recommended to use the App in students with moderate or low learning motivation to promote learning effectiveness.}, } @article {pmid36153396, year = {2022}, author = {Malekhosseini, M and Ensikat, HJ and McCoy, VE and Wappler, T and Weigend, M and Kunzmann, L and Rust, J}, title = {Traces of calcium oxalate biomineralization in fossil leaves from late Oligocene maar deposits from Germany.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {15959}, pmid = {36153396}, issn = {2045-2322}, mesh = {Biomineralization ; Calcium ; *Calcium Oxalate/chemistry ; Crystallization ; *Fossils ; Minerals ; Plant Leaves ; Plants ; }, abstract = {Calcium oxalate (CaOx) is one of the most common bio-mineral in extant plants and is believed to serve a variety of functions such as calcium storage and herbivore defense. However, traces of CaOx crystals have rarely been identified in fossil plants, and they are primarily known from fossil gymnosperms, where empty cavities of former CaOx crystals or ghost crystals have been reported from leaf cuticles of some Late Cretaceous and Cenozoic conifers. Here we investigate fossil angiosperm leaves from the late Oligocene Rott Fossil Lagerstätte and report ghost crystals of various shapes, sizes and topology (distribution patterns), and cavities. These micromorphological structures of fossil leaves are compared to CaOx deposits in leaves of extant plants: globular structures in fossil leaves resemble CaOx druses (crystal aggregates) in fresh leaves in size and distribution; and angular or brick-shaped structures in the vascular system of fossil leaves closely resemble prismatic CaOx crystals in the vascular system of extant leaves in both size and topology. Chemically, CaOx druses have survived fossilization as cavities only, and were replaced by organic matter and ghost minerals containing Ca, Si, Al, S, and Fe. The identification of former CaOx remains in leaf fossils provides novel insights on the fate of plant bio-minerals during fossilization. More importantly, it provides an additional aspect of the ecophysiology of fossil plants thus improving the accuracy of palaeoecological reconstructions and can provide a broader perspective on the evolution of CaOx and their rule in plant ecology across geological timescales. Alternative interpretations of the fossil microstructures are discussed but ruled out.}, } @article {pmid36153165, year = {2023}, author = {Olmos-Ochoa, TT and Luger, TM and Oishi, A and Dyer, KE and Sumberg, A and Canelo, I and Gideonse, TK and Cheney, A and Yano, EM and Hamilton, AB}, title = {Challenges to Engaging Women Veterans in Quality Improvement From Patient Care to Policy: Women's Health Managers' Perspectives.}, journal = {Women's health issues : official publication of the Jacobs Institute of Women's Health}, volume = {33}, number = {2}, pages = {199-207}, doi = {10.1016/j.whi.2022.08.004}, pmid = {36153165}, issn = {1878-4321}, mesh = {Humans ; Female ; *Patient Care ; Health Policy ; *Quality Improvement ; United States Department of Veterans Affairs ; United States ; *Veterans Health ; Women ; Women's Health ; Veterans ; }, abstract = {INTRODUCTION: Patients are uniquely positioned to identify issues and to provide innovative solutions to problems impacting their care. Yet, patient engagement in quality improvement (QI) and health care governance remains limited and underexplored. In the Veterans Health Administration, the work of women's health managers (WHMs) includes engaging women veterans, a numerical minority with unique health care needs, in QI. We aimed to understand the extent to which WHMs engage women veterans along a continuum, highlight challenges to engagement, and identify potential strategies to facilitate multilevel patient engagement.

METHODS: Data were generated from a multisite evaluation to improve delivery of comprehensive women's health care in Veterans Health Administration primary care sites. We conducted 39 semistructured interviews with WHMs across 21 sites. Guided by Carman et al.'s patient engagement framework, we analyzed the interviews using rapid-qualitative and content analysis methods.

RESULTS: When effectively engaged, women veterans were important champions and partners in QI activities to improve the structure and delivery of care. However, most WHMs engaged women veterans in mainly informal or passive ways-that is, solicited feedback through comment cards, surveys, focus groups, and townhall meetings-and did not report pursuing more in-depth or long-term forms of engagement. WHMs also identified a variety of facilitators and challenges to engaging women veterans in QI.

CONCLUSIONS: There may be unanticipated benefits to health care policy from engaging patients in QI, especially for patients with unique health care needs who represent a minority within the health care system. However, managers require training and workflow integration of patient engagement tasks to increase their efficiency and allow for meaningful patient engagement.}, } @article {pmid36149039, year = {2022}, author = {Banti, S and Sumathy, TK and Pramila, K}, title = {Insulin resistance in various grades of acanthosis nigricans.}, journal = {Acta dermatovenerologica Alpina, Pannonica, et Adriatica}, volume = {31}, number = {3}, pages = {101-104}, pmid = {36149039}, issn = {1581-2979}, mesh = {*Acanthosis Nigricans/complications/diagnosis ; Adolescent ; Adult ; Blood Glucose/metabolism ; Humans ; Insulin/metabolism ; *Insulin Resistance ; *Insulins ; Lipids ; Middle Aged ; Triglycerides ; Young Adult ; }, abstract = {INTRODUCTION: Insulin resistance (IR) is a metabolism disorder that contributes to the pathophysiology of acanthosis nigricans (AN). In turn, AN is a self-determining risk factor and cutaneous marker of IR. However, conflicting evidence makes the AN-IR relationship debatable and open to exploration. If established, it could provide opportunities for early diagnosis and management of IR before the onset of diabetes mellitus and its complications by screening AN patients. This study investigates the prevalence of IR among AN patients and evaluates the association between IR and AN severity.

METHODS: Eighty-seven patients, 18 to 60 years old, with untreated AN and absence of diabetes mellitus, underwent detailed history, systemic, and cutaneous examinations, as well as measurement of their body mass index (BMI), waist and hip circumference and their ratio (WHR), fasting blood glucose (FBG) and lipid profile, fasting serum insulin levels, and quantitative insulin-sensitivity check index (QUICKI). Severity of the neck lesions was graded according to Burke et al.'s grading system.

RESULTS: AN was noted most commonly in younger age groups with 93.1% of the cases younger than 45. All patients had lesions on the neck, and 63.3% of the cases had multiple site involvement. Nearly 84% of the cases were overweight or obese. AN grades exhibited a significant positive association with BMI (p = 0.002) and WHR (p = 0.016). High IR (< 0.35 QUICKI) was seen in 55 (63.2%) AN patients. IR, QUICKI, and triglyceride levels showed no significant association with AN severity and the number of AN lesion sites (p > 0.05). LDL levels (p = 0.02) and WHR (p = 0.049) showed a significant positive association with the number of AN lesion sites, but not with AN severity grading (p > 0.05).

CONCLUSIONS: IR is present in AN patients, but the association between IR and AN severity is not significant enough to qualify AN as a screening tool for IR.}, } @article {pmid36136770, year = {2022}, author = {Scott, LN}, title = {What are we missing in dimensional models that might explain core dynamic processes in borderline personality disorder? Commentary on Miskewicz et al. (2022).}, journal = {Personality disorders}, volume = {13}, number = {5}, pages = {445-446}, pmid = {36136770}, issn = {1949-2723}, support = {R01 MH115922/MH/NIMH NIH HHS/United States ; }, mesh = {*Borderline Personality Disorder ; Humans ; }, abstract = {Comments on the original article by Miskewicz et al. (see record 2021-98114-001) regarding dimensional models that might explain core dynamic processes in borderline personality disorder. Miskewicz et al.'s findings provide strong evidence that although dynamic processes in borderline personality disorderare important, a trait-only model cannot fully explain core dynamic processes underlying symptom fluctuations as a function of context in borderline personality disorder (BPD). In fact, any single model is likely insufficient to explain BPD functioning in all its complexity. An important next step is to examine how traits and other theoretically and empirically informed constructs might synergistically (rather than merely independently) explain the dynamic expression of BPD symptoms in real-world contexts. (PsycInfo Database Record (c) 2022 APA, all rights reserved).}, } @article {pmid36128713, year = {2023}, author = {Sanatkar, S and Rubin, M}, title = {An exploratory investigation of the reliability and validity of the Independent-Interdependent Problem-Solving Style Scale.}, journal = {International journal of psychology : Journal international de psychologie}, volume = {58}, number = {1}, pages = {30-41}, pmid = {36128713}, issn = {1464-066X}, mesh = {Humans ; Reproducibility of Results ; Psychometrics ; *Personality ; *Problem Solving ; Surveys and Questionnaires ; }, abstract = {The Independent-Interdependent Problem-Solving Scale is based on Cross et al.'s conceptualisation of relational-interdependent self-construal. The IIPSS provides a relatively context-free measure of people's tendencies to solve problems independently or with the help of others. Because previous investigations have not provided extensive evidence for the reliability and validity of the IIPSS, the current research aimed to test the psychometric properties of this novel measure. Investigations of four student samples (combined N = 1157) and one sample comprised of academic researchers (N = 198) generally supported the reliability and validity of the IIPSS. Exploratory factor analysis of IIPSS items yielded a single factor structure. However, confirmatory factor analyses did not demonstrate good model fit for the one factor solution and instead yielded good model fit for two underlying factors. The IIPSS showed adequate test-retest reliability and predicted positive associations with social personality traits. It also showed no significant associations with measures of demand characteristics and social desirability. Future research needs to be undertaken to further assess the factor structure and address shortcomings of the present research such as utilising objective data in addition to self-reports to assess the scale's validity.}, } @article {pmid36126538, year = {2022}, author = {Bellew, D and Davenport, L and Monaghan, R and Cogley, C and Gaughan, M and Yap, SM and Tubridy, N and Bramham, J and McGuigan, C and O'Keeffe, F}, title = {Interpreting the clinical importance of the relationship between subjective fatigue and cognitive impairment in multiple sclerosis (MS): How BICAMS performance is affected by MS-related fatigue.}, journal = {Multiple sclerosis and related disorders}, volume = {67}, number = {}, pages = {104161}, doi = {10.1016/j.msard.2022.104161}, pmid = {36126538}, issn = {2211-0356}, mesh = {Humans ; *Multiple Sclerosis/complications/psychology ; Neuropsychological Tests ; *Cognitive Dysfunction/etiology/complications ; Fatigue/complications ; Cognition ; }, abstract = {BACKGROUND: There is evidence that subjective fatigue can influence cognitive functioning in multiple sclerosis (MS). DeLuca et al.'s (2004) Relative Consequence Model proposes that impairments to other high-level cognitive functions, such as memory, result from the disease's effect on information processing speed.

OBJECTIVE: The primary aims of the study were to investigate both 1) the relationship between subjective fatigue and cognitive functioning, as measured by the widely used Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) in MS; and 2) the consequential effect of fatigue on information processing speed as predicted by the Relative Consequence Model.

METHODS: 192 participants with MS attending tertiary referral MS centre completed the Modified Fatigue Impact Scale and BICAMS.

RESULTS: Multiple correlation analyses determined that there were statistically significant relationships between all domains assessed by the BICAMS and levels of fatigue, such that higher levels of self-reported fatigue were associated with lower performance on information-processing, and visual and verbal learning. After controlling for information processing speed, the strength of correlation between fatigue and learning performance weakened. Linear regression analysis showed that fatigue predicted the most variance in verbal learning and 11.7% of the overall variance in BICAMS performance.

CONCLUSION: Subjective fatigue and objective cognitive performance in MS are related. Caution is advised in the interpretation of BICAMS scores in cases where high levels of fatigue are present, and more detailed neuropsychological assessments may be required in order to accurately identify objective cognitive impairment independent of subjective fatigue.}, } @article {pmid36125984, year = {2022}, author = {Ledesma, JR and Lurie, P and Yorlets, RR and Daly, G and Chrysanthopoulou, S and Lurie, MN}, title = {Spurious early ecological association suggesting BCG vaccination effectiveness for COVID-19.}, journal = {PloS one}, volume = {17}, number = {9}, pages = {e0274900}, pmid = {36125984}, issn = {1932-6203}, support = {P2C HD041020/HD/NICHD NIH HHS/United States ; }, mesh = {BCG Vaccine ; *COVID-19/epidemiology/prevention & control ; Humans ; SARS-CoV-2 ; *Tuberculosis/epidemiology ; Vaccination ; }, abstract = {BACKGROUND: Several ecologic studies have suggested that the bacillus Calmette-Guérin (BCG) vaccine may be protective against SARS-CoV-2 infection including a highly-cited published pre-print by Miller et al., finding that middle/high- and high-income countries that never had a universal BCG policy experienced higher COVID-19 burden compared to countries that currently have universal BCG vaccination policies. We provide a case study of the limitations of ecologic analyses by evaluating whether these early ecologic findings persisted as the pandemic progressed.

METHODS: Similar to Miller et al., we employed Wilcoxon Rank Sum Tests to compare population medians in COVID-19 mortality, incidence, and mortality-to-incidence ratio between countries with universal BCG policies compared to those that never had such policies. We then computed Pearson's r correlations to evaluate the association between year of BCG vaccination policy implementation and COVID-19 outcomes. We repeated these analyses for every month in 2020 subsequent to Miller et al.'s March 2020 analysis.

RESULTS: We found that the differences in COVID-19 burden associated with BCG vaccination policies in March 2020 generally diminished in magnitude and usually lost statistical significance as the pandemic progressed. While six of nine analyses were statistically significant in March, only two were significant by the end of 2020.

DISCUSSION: These results underscore the need for caution in interpreting ecologic studies, given their inherent methodological limitations, which can be magnified in the context of a rapidly evolving pandemic in which there is measurement error of both exposure and outcome status.}, } @article {pmid36106693, year = {2022}, author = {Staubitz, JL and Staubitz, JE and Pollack, MS and Haws, RA and Hopton, M}, title = {Effects of an enhanced choice model of skill-based treatment for students with emotional/behavioral disorders.}, journal = {Journal of applied behavior analysis}, volume = {55}, number = {4}, pages = {1306-1341}, doi = {10.1002/jaba.952}, pmid = {36106693}, issn = {1938-3703}, mesh = {Behavior Therapy/methods ; Child ; Humans ; *Mental Disorders ; *Problem Behavior ; Schools ; Students/psychology ; }, abstract = {The enhanced choice model of skill-based treatment (ECM-SBT; Rajaraman et al., 2021) is a package of behavioral treatment procedures with modifications designed to reduce risks associated with extinction of problem behavior. The skill-based treatment component of this package (Hanley et al., 2014) has been investigated thoroughly in clinical settings, though fewer studies have been conducted in public schools. In this investigation, we systematically replicated Rajaraman et al.'s (2021) demonstration of the ECM-SBT with 3 children enrolled in a public special day school for students with emotional and behavioral disorders. Intervention procedures were associated with increases in targeted alternative responses (i.e., communicative response, tolerance response, and cooperation with instructions) and decreased precursor behavior relative to baseline. Severe problem behavior was rare in both assessment and treatment. Participants chose to spend most appointment time participating in ECM-SBT, indicating preference for treatment procedures over alternative contexts (i.e., free access to a break area with preferred activities; regular classroom instruction). These outcomes suggest ECM-SBT has promise for safely teaching alternatives to problem behavior to children with emotional and behavioral disorders in school settings.}, } @article {pmid36103234, year = {2022}, author = {Strasser, R}, title = {Commentary: Burning Platforms, Icebergs and Tipping Points - Canada Needs a Single Socially Accountable Healthcare System.}, journal = {Healthcare policy = Politiques de sante}, volume = {18}, number = {1}, pages = {26-31}, pmid = {36103234}, issn = {1715-6580}, mesh = {Aged ; Canada ; *Delivery of Health Care ; Humans ; *National Health Programs ; Quality of Health Care ; Social Responsibility ; }, abstract = {Leslie et al.'s (2022) article caused me to reflect on the complexities and contradictions that are Canada. Healthcare in Canada is a hodgepodge of different health systems all assembled under the umbrella of the Canada Health Act (1985). Canadians expect medicare to deliver high-quality healthcare close to home wherever they live. For this aspiration to become a reality, there needs to be a single pan-Canadian health system focussed on the health needs of the populations being served. This socially accountable healthcare system is likely to be achieved only if there is a chorus of support across Canada for meaningful pan-Canadian health reforms.}, } @article {pmid36101740, year = {2022}, author = {Ben Cheikh, N and Ben Zaied, Y and Saidi, S and Sellami, M}, title = {Global pandemic crisis and risk contagion in GCC stock markets.}, journal = {Journal of economic behavior & organization}, volume = {202}, number = {}, pages = {746-761}, pmid = {36101740}, issn = {0167-2681}, abstract = {This study investigates how the COVID-19 outbreak has shaped the volatility spillover between oil and Gulf Cooperation Council (GCC) stock markets. Contagion analysis is conducted by implementing a vector error correction (VECM) asymmetric BEKK model, wherein both cointegration and asymmetric features are considered. Financial market uncertainty caused by the recent health crisis is captured using Baker et al.'s (2020) newly developed infectious disease tracker. Our results indicate a significant discrepancy in the GCC group, as shock and volatility linkages between oil and equities are more apparent for some countries but not for others. The estimated VECM-asymmetric BEKK model reveals cross-market asymmetric spillover effects only in Kuwait, Qatar, and Saudi Arabia. We report that the global pandemic has strongly affected crude oil market volatility, while the GCC region seems to be less affected by the emergence of the new infectious disease. Our findings underscore the diversification opportunities offered by Gulf equity markets to international investors.}, } @article {pmid36098503, year = {2022}, author = {Shvarev, D and Schoppe, J and König, C and Perz, A and Füllbrunn, N and Kiontke, S and Langemeyer, L and Januliene, D and Schnelle, K and Kümmel, D and Fröhlich, F and Moeller, A and Ungermann, C}, title = {Structure of the HOPS tethering complex, a lysosomal membrane fusion machinery.}, journal = {eLife}, volume = {11}, number = {}, pages = {}, pmid = {36098503}, issn = {2050-084X}, mesh = {*Membrane Fusion ; *Saccharomyces cerevisiae Proteins/metabolism ; Saccharomyces cerevisiae/metabolism ; Cryoelectron Microscopy ; rab GTP-Binding Proteins/metabolism ; SNARE Proteins/metabolism ; Lysosomes/metabolism ; Vacuoles/metabolism ; }, abstract = {Lysosomes are essential for cellular recycling, nutrient signaling, autophagy, and pathogenic bacteria and viruses invasion. Lysosomal fusion is fundamental to cell survival and requires HOPS, a conserved heterohexameric tethering complex. On the membranes to be fused, HOPS binds small membrane-associated GTPases and assembles SNAREs for fusion, but how the complex fulfills its function remained speculative. Here, we used cryo-electron microscopy to reveal the structure of HOPS. Unlike previously reported, significant flexibility of HOPS is confined to its extremities, where GTPase binding occurs. The SNARE-binding module is firmly attached to the core, therefore, ideally positioned between the membranes to catalyze fusion. Our data suggest a model for how HOPS fulfills its dual functionality of tethering and fusion and indicate why it is an essential part of the membrane fusion machinery.}, } @article {pmid36095136, year = {2022}, author = {Yin, L and Cui, J and Lin, X and Li, N and Fan, Y and Zhang, L and Liu, J and Chong, F and Wang, C and Liang, T and Liu, X and Deng, L and Yang, M and Yu, J and Wang, X and Cong, M and Li, Z and Weng, M and Yao, Q and Jia, P and Guo, Z and Li, W and Song, C and Shi, H and Xu, H}, title = {Identifying cancer cachexia in patients without weight loss information: machine learning approaches to address a real-world challenge.}, journal = {The American journal of clinical nutrition}, volume = {116}, number = {5}, pages = {1229-1239}, doi = {10.1093/ajcn/nqac251}, pmid = {36095136}, issn = {1938-3207}, mesh = {Male ; Female ; Humans ; Middle Aged ; *Cachexia/diagnosis/etiology ; Cohort Studies ; Retrospective Studies ; *Neoplasms/complications ; Weight Loss ; Machine Learning ; }, abstract = {BACKGROUND: Diagnosing cancer cachexia relies extensively on patient-reported historic weight, and failure to accurately recall this information can lead to severe underestimation of cancer cachexia.

OBJECTIVES: The present study aimed to develop inexpensive tools to facilitate the identification of cancer cachexia in patients without weight loss information.

METHODS: This multicenter cohort study included 12,774 patients with cancer. Cachexia was retrospectively diagnosed using Fearon et al.'s framework. Baseline clinical features, excluding weight loss, were modeled to mimic a situation where the patient is unable to recall their weight history. Multiple machine learning (ML) models were trained using 75% of the study cohort to predict cancer cachexia, with the remaining 25% of the cohort used to assess model performance.

RESULTS: The study enrolled 6730 males and 6044 females (median age = 57.5 y). Cachexia was diagnosed in 5261 (41.2%) patients and most diagnoses were made based on the weight loss criterion. A 15-variable logistic regression (LR) model mainly comprising cancer types, gastrointestinal symptoms, tumor stage, and serum biochemistry indexes was selected among the various ML models. The LR model showed good performance for predicting cachexia in the validation data (AUC = 0.763; 95% CI: 0.747, 0.780). The calibration curve of the model demonstrated good agreement between predictions and actual observations (accuracy = 0.714, κ = 0.396, sensitivity = 0.580, specificity = 0.808, positive predictive value = 0.679, negative predictive value = 0.733). Subgroup analyses showed that the model was feasible in patients with different cancer types. The model was deployed as an online calculator and a nomogram, and was exported as predictive model markup language to permit flexible, individualized risk calculation.

CONCLUSIONS: We developed an ML model that can facilitate the identification of cancer cachexia in patients without weight loss information, which might improve decision-making and lead to the development of novel management strategies in cancer care. This trial was registered at https://www.chictr.org.cn as ChiCTR1800020329.}, } @article {pmid36094666, year = {2023}, author = {Kerzel, D and Renaud, O}, title = {Does attentional suppression occur at the level of perception or decision-making? Evidence from Gaspelin et al.'s (2015) probe letter task.}, journal = {Psychological research}, volume = {87}, number = {4}, pages = {1243-1255}, pmid = {36094666}, issn = {1430-2772}, support = {100019_182146//Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung/ ; }, mesh = {Female ; Humans ; Male ; Young Adult ; *Attentional Bias/physiology ; Choice Behavior/physiology ; Cues ; *Decision Making/physiology ; Mental Recall/physiology ; Photic Stimulation ; Reaction Time ; Reproducibility of Results ; *Visual Perception/physiology ; Adolescent ; Adult ; }, abstract = {Visual attention is often inadvertently captured by salient stimuli. It was suggested that it is possible to prevent attentional capture in some search tasks by suppressing salient stimuli below baseline. Evidence for attentional suppression comes from a probe task that was interleaved with the main search task. In the probe task of Gaspelin et al. (Psychol Sci 26(11):1740-1750, 2015. https://doi.org/10.1177/0956797615597913), letters were shown on the stimuli of the search display and participants had to identify as many letters as possible. Performance was found to be worse for letters shown on the distractor compared to non-salient non-target stimuli, suggesting that distractor processing was suppressed below baseline. However, it is unclear whether suppression occurred at the level of perception or decision-making because participants may have reported letters on the distractor less frequently than letters on nontargets. This decision-level bias may have degraded performance for letters on distractor compared to nontarget stimuli without changing perception. After replicating the original findings, we conducted two experiments where we avoided report bias by cueing only a single letter for report. We found that the difference between distractor and nontarget stimuli was strongly reduced, suggesting that decision-level processes contribute to attentional suppression. In contrast, the difference between target and non-target stimuli was unchanged, suggesting that it reflected perceptual-level enhancement of the target stimuli.}, } @article {pmid36076194, year = {2022}, author = {Ren, X and Zhang, X and He, Q and Du, L and Chen, K and Chen, S and Pan, Y}, title = {Prevalence of sarcopenia in Chinese community-dwelling elderly: a systematic review.}, journal = {BMC public health}, volume = {22}, number = {1}, pages = {1702}, pmid = {36076194}, issn = {1471-2458}, mesh = {Aged ; China/epidemiology ; Humans ; Independent Living ; Prevalence ; *Sarcopenia/diagnosis/epidemiology ; Surveys and Questionnaires ; }, abstract = {BACKGROUND: Sarcopenia is associated with age-related loss of muscle mass and function and is becoming prevalent in the older Chinese population. This systematic review aims to obtain a reliable estimation of the prevalence of sarcopenia among community-dwelling Chinese populations aged 65 years and older and to characterize its epidemiology.

METHODS: A literature search was performed in the Cochrane Library, PubMed, Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang Data, and CQVIP databases up to September 31, 2021. All studies that reported the prevalence of sarcopenia in Chinese community-dwelling older adults were included, and Hoy et al.'s tool was used to assess the risk of bias. The overall prevalence of sarcopenia will be calculated as the primary outcome, and subgroup analyses will be performed by study year, age, sex, muscle mass assessment method, diagnostic criteria and area.

RESULTS: A total of 26 studies were included in this study, which involved 25,921 subjects, and 3597 had sarcopenia. Although significant heterogeneity between studies was reported, no statistically significant publication bias was detected. The overall prevalence of sarcopenia in community-dwelling older adults aged over 65 years in the Chinese population was 17.4% (95% CI: 14.6%-20.2%). Subgroup analysis based on study year, age and sex, muscle mass assessment method, diagnostic criteria, region and area showed that the prevalence of sarcopenia was different in each subgroup.

IMPLICATIONS: The prevalence of sarcopenia in Chinese community-dwelling older adults was higher than that in previous studies. As a multidimensional survey of the prevalence of sarcopenia in older adults, this meta-analysis provides data support for the targeted management of sarcopenia among Chinese older adults.}, } @article {pmid36075279, year = {2022}, author = {Collins, MS and Ezemma, O and Devjani, S and Senna, MM}, title = {Reply to "Response to Collins et al.'s 'Retrospective review of adverse events associated with oral hydroxychloroquine use in patients with cicatricial alopecia'".}, journal = {Journal of the American Academy of Dermatology}, volume = {87}, number = {6}, pages = {e221}, doi = {10.1016/j.jaad.2022.08.058}, pmid = {36075279}, issn = {1097-6787}, mesh = {Humans ; *Hydroxychloroquine/adverse effects ; Retrospective Studies ; *Alopecia/drug therapy/complications ; Cicatrix/pathology ; }, } @article {pmid36072040, year = {2022}, author = {Yang, S and Han, J}, title = {Perspectives of transformative learning and professional agency: A native Chinese language teacher's story of teacher identity transformation in Australia.}, journal = {Frontiers in psychology}, volume = {13}, number = {}, pages = {949673}, pmid = {36072040}, issn = {1664-1078}, abstract = {The notion of teacher identity has gained momentum in second language (L2) teacher education in the past decade. However, the research into Chinese as a Foreign Language (CFL) teacher identity has yet to receive more attention. The study employed a narrative inquiry to explore a native Chinese CFL in-service teacher's identity negotiation and transformation within an international teacher education program. Self-reported narrative accounts, including multiple in-depth interviews and once-a-term reflective journals, were complemented by field notes and program documents. This data captured how the participant teacher negotiated internally with self and externally with the new environment to pursue professional growth. Mezirow's transformative learning theory was used to reveal the cognitive trajectory of the participant's teacher identity transformation with critical reflection as the central stage. Further, guided by Eteläpelto et al.'s framework of professional agency, the study also unraveled multiple external and internal influences on the transformational trajectory. The findings confirmed the value of integrating these two theoretical perspectives to explore language teacher identity development and offer insights into L2 teacher education practices focusing on teacher identity development.}, } @article {pmid36066677, year = {2022}, author = {Sullins, DP}, title = {Sexual Orientation Change Efforts Do Not Increase Suicide: Correcting a False Research Narrative.}, journal = {Archives of sexual behavior}, volume = {51}, number = {7}, pages = {3377-3393}, pmid = {36066677}, issn = {1573-2800}, mesh = {Female ; Homosexuality ; Humans ; Male ; Risk Factors ; Sexual Behavior ; *Sexual and Gender Minorities ; Suicidal Ideation ; *Suicide, Attempted ; }, abstract = {Sexual orientation change efforts (SOCEs) signify activities designed to change or reduce homosexual orientation. Recent studies have claimed that such therapies increase suicide risk by showing positive associations between SOCE and lifetime suicidality, without excluding behavior that pre-dated SOCE. In this way, Blosnich et al.'s (2020) recent analysis of a national probability sample of 1518 sexual minority persons concluded that SOCE "may compound or create…suicidal ideation and suicide attempts" but after correcting for pre-existing suicidality, SOCE was not positively associated with any form of suicidality. For suicidal ideation, Blosnich et al. reported an adjusted odds ratio (AOR) of 1.92 (95% CI 1.01-3.64); the corrected AOR was .44 (.20-.94). For suicide planning, Blosnich et al.'s AOR was 1.75 (1.01-3.06); corrected was .60 (.32-1.14). For suicide attempts, Blosnich et al.'s AOR was 1.75 (.99-3.08); corrected was .74 (.36-1.43). Undergoing SOCE after expressing suicidal behavior reduced subsequent suicide attempts from 72 to 80%, compared to those not undergoing SOCE, when SOCE followed a prior expression of suicidal ideation (AOR .17, .05-.55), planning (AOR .13, .04-.45) or intention (AOR .10, .03-.30); however, SOCE following an initial suicide attempt did not significantly reduce further attempts. By violating the principle that a cause cannot occur after an effect, Blosnich et al. misstated the correct conclusion. Experiencing SOCE does not result in higher suicidality, as they claim, and may sharply reduce subsequent suicide attempts. Restrictions on SOCE will not reduce suicidal risk among sexual minorities and may deprive them of an important resource for reducing suicide attempts.}, } @article {pmid36057434, year = {2022}, author = {Saberi, K and Hickok, G}, title = {Confirming an antiphasic bicyclic pattern of forward entrainment in signal detection: A reanalysis of Sun et al. (2021).}, journal = {The European journal of neuroscience}, volume = {56}, number = {8}, pages = {5274-5286}, pmid = {36057434}, issn = {1460-9568}, support = {R01 DC003681/DC/NIDCD NIH HHS/United States ; R01 DC009659/DC/NIDCD NIH HHS/United States ; }, mesh = {*Fourier Analysis ; }, abstract = {Forward entrainment refers to that part of the entrainment process that persists after termination of an entraining stimulus. Hickok et al. (2015) reported forward entrainment in signal detection that lasted for two post-stimulus cycles. In a recent paper, Sun et al. (2021) reported new data which suggested an absence of entrainment effects (Eur. J. Neurosci, 1-18, doi.org/10.1111/ejn.15367). Here we show that when Sun et al.'s data are analysed using unbiased detection-theoretic measures, a clear antiphasic bicyclic pattern of entrainment is observed. We further show that the measure of entrainment strength used by Sun et al., the normalized Fourier transform of performance curves, is not only erroneously calculated but is also unreliable in estimating entrainment strength due to signal-processing artifacts.}, } @article {pmid36054132, year = {2022}, author = {Mamdani, Z and Feldman-Kiss, D and McKenzie, S and Knott, M and Cameron, F and Voyer, R and van Norren, J and Scott, T and Pauly, B and Buxton, JA}, title = {Core competencies of peer workers who use pulse oximeters to supplement their overdose response in British Columbia.}, journal = {PloS one}, volume = {17}, number = {9}, pages = {e0273744}, pmid = {36054132}, issn = {1932-6203}, mesh = {British Columbia ; *Drug Overdose ; Humans ; *Oximetry ; Oxygen ; Peer Group ; }, abstract = {INTRODUCTION: Peer workers (those with lived/living experience of substance use) are at the forefront of overdose response initiatives in British Columbia, Canada. The onset of the coronavirus disease pandemic has significantly compounded the impact of the overdose crisis. Peer workers are integral in supporting people who use substances. However, despite the important work they do, peer workers often lack formalized credibility and do not have the same resources available to them as service providers without lived experience. The peer-led project titled the Peer2Peer Project implemented several support programs for peer workers, including providing pulse oximeters to peer workers to supplement their overdose response procedures.

MATERIALS AND METHODS: This study was a component of a larger evaluation of the pulse oximeter program at two organizations in BC. The study aims to highlight the competencies of peer workers who use pulse oximeters. Telephone interviews were conducted with seven peer workers who were given pulse oximeters. The transcripts were thematically coded using Covert et al.'s framework of core competencies of community health workers to compare our sample with other widely recognized professions.

FINDINGS: We found that peer workers who used pulse oximeters described several core competencies in their work and these were aligned with Covert et al.'s core competencies for community health workers, including assessment, community health practice, communication, diversity and inclusion, professional practice, and disease prevention and management.

CONCLUSION: By aligning peer workers' skills to those of community health workers, we create awareness on the competencies of peer workers in using oximeters to supplement overdose response and advocate for them to receive more recognition and respect within the workplace. Further, our findings act as groundwork for future research in identifying the professional proficiencies of peer workers.}, } @article {pmid36052511, year = {2022}, author = {Ketcheson, LR and Pitchford, EA and Staples, KL and MacDonald, M and Ulrich, DA}, title = {Supporting the need for the motor domain to be included in the definition of autism spectrum disorder: A response to Bishop et al.'s critique of Bhat (2021).}, journal = {Autism research : official journal of the International Society for Autism Research}, volume = {15}, number = {10}, pages = {1796-1798}, doi = {10.1002/aur.2811}, pmid = {36052511}, issn = {1939-3806}, mesh = {*Autism Spectrum Disorder/diagnosis ; Humans ; }, } @article {pmid36034312, year = {2022}, author = {Levin, LA and Patrick, C and Choudry, NB and Sharif, NA and Goldberg, JL}, title = {Neuroprotection in neurodegenerations of the brain and eye: Lessons from the past and directions for the future.}, journal = {Frontiers in neurology}, volume = {13}, number = {}, pages = {964197}, pmid = {36034312}, issn = {1664-2295}, support = {P30 EY026877/EY/NEI NIH HHS/United States ; }, abstract = {BACKGROUND: Neurological and ophthalmological neurodegenerative diseases in large part share underlying biology and pathophysiology. Despite extensive preclinical research on neuroprotection that in many cases bridges and unifies both fields, only a handful of neuroprotective therapies have succeeded clinically in either.

MAIN BODY: Understanding the commonalities among brain and neuroretinal neurodegenerations can help develop innovative ways to improve translational success in neuroprotection research and emerging therapies. To do this, analysis of why translational research in neuroprotection fails necessitates addressing roadblocks at basic research and clinical trial levels. These include optimizing translational approaches with respect to biomarkers, therapeutic targets, treatments, animal models, and regulatory pathways.

CONCLUSION: The common features of neurological and ophthalmological neurodegenerations are useful for outlining a path forward that should increase the likelihood of translational success in neuroprotective therapies.}, } @article {pmid36029706, year = {2022}, author = {Al-Chalabi, M and DelCimmuto, NR and Beran, A and Devarasetty, PP and Mhanna, A and Mahfooz, N and Sheikh, A}, title = {Clinical characteristics, management, and outcomes of CLIPPERS: A comprehensive systematic review of 140 patients from 100 studies.}, journal = {Multiple sclerosis and related disorders}, volume = {68}, number = {}, pages = {104112}, doi = {10.1016/j.msard.2022.104112}, pmid = {36029706}, issn = {2211-0356}, mesh = {Middle Aged ; Male ; Humans ; Adult ; *Magnetic Resonance Imaging ; Prospective Studies ; *Pons/pathology ; Inflammation/drug therapy ; Steroids/therapeutic use ; Syndrome ; Chronic Disease ; }, abstract = {INTRODUCTION: Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a rare inflammatory disorder of the central nervous system, characterized by symptoms referable to the brainstem and cerebellum such as, diplopia, gait ataxia and cerebellar dysarthria. The features and outcomes of CLIPPERS remains uncertain. we conducted this comprehensive systematic review to summarize all the existing studies that described CLIPPERS in the literature and to provide a quantitative assessment on the clinical characteristics, management, and outcomes of this rare syndrome.

METHODS: A comprehensive search of PubMed and Web of Science databases was conducted from inception until January 15, 2022, was conducted. We only included the cases that clearly reported probable or definite diagnosis of CLIPPERS based on Taieb et al.'s criteria. The quality of the included studies was assessed using the JBI Critical Appraisal Tool. Descriptive statistics were performed to analyze the studies. Data were expressed as mean and standard deviation (SD) for continuous variables and proportions for categorical variables.

RESULTS: We identified 100 case reports and series including a total of 140 patients with CLIPPERS (mean age: 46±18 years and males were 60%). The average follow-up duration was 32.27±57.8 months. Ataxia was the most common presenting symptom. Sixteen percent of the cases were associated with malignancy, mostly hematologic malignancies. The overall relapse rate was 59.2%, and the duration of steroid therapy was considerably shorter in the relapsed cases than in the non-relapsed (mean 6.19±7.9 vs. 10.14±12.1 days, respectively, P = 0.04). The overall mortality rate was 10%, but mortality in patients with malignancy was 30% and it was 12% in patients with relapses. In the case of steroid dosing (less than 20 mg/d versus greater than 20 mg/d) there was no significant modification in the risk of relapse.

CONCLUSION: CLIPPERS is a rare clinical syndrome that affects mainly middle-aged males. Diagnosis of CLIPPERS is often challenging, and delays in diagnosis and treatment can lead to unfavorable outcomes. Therefore, neurologists should maintain a high index of suspicion for CLIPPERS in any patient presenting with symptoms and signs referrable to the brainstem. These patients should be screened for associated malignancies, especially hematological malignancies. The cases associated with malignancy tend to have worse outcomes. The relapse rate is relatively high. The relapse rate may be associated with worse mortality. Based on our findings, we recommend that CLIPPERS be treated with high-dose steroid therapy for at least ten days during the acute phase with a very slow taper. Prospective studies with a larger sample size are needed to validate our findings and guide the clinical care of these patients.}, } @article {pmid36027793, year = {2022}, author = {Xue, T and Wu, X and Chen, S and Zhang, J and Chen, Z and Wang, Z}, title = {Reply to Wang et al.'s commentary on Xue et al.: The efficacy and safety of dual orexin receptor antagonists in primary insomnia: A systematic review and network meta-analysis.}, journal = {Sleep medicine reviews}, volume = {65}, number = {}, pages = {101686}, doi = {10.1016/j.smrv.2022.101686}, pmid = {36027793}, issn = {1532-2955}, } @article {pmid36018386, year = {2023}, author = {Scheuermann, JS and Gräßel, E and Pendergrass, A}, title = {Predictors of expressed, felt, and normative needs for informal caregiver counseling : Domestic care for people aged 65+ years.}, journal = {Zeitschrift fur Gerontologie und Geriatrie}, volume = {56}, number = {5}, pages = {395-401}, pmid = {36018386}, issn = {1435-1269}, mesh = {Humans ; Male ; *Caregivers/psychology ; *Dementia/psychology ; Cross-Sectional Studies ; Adaptation, Psychological ; Counseling ; }, abstract = {BACKGROUND: Informal caregivers (CGs) often fail to recognize or express a need for informal caregiver counseling (ICC) but ICC is an essential but relatively rarely used support service for CGs.

OBJECTIVE: Our aim is to identify predictors of CGs' need for ICC. Stirling et al.'s need model, which includes three needs (expressed, felt, and normative), serves as a theoretical basis.

MATERIAL AND METHODS: Analyses are based on cross-sectional data (n = 958) from the "Benefits of being a caregiver" study. Predictors of the need to use ICC were analyzed with binary logistic regression. A sensitivity analysis using multiple linear regression was performed for the metric value of normative needs.

RESULTS: We found that 6.8% of CGs currently or have recently used ICC. This expressed need was related to higher education and higher effort in instrumental activities; 24.1% of CGs reported an intention to use ICC in the future. This felt need was related to male gender, lower care level, more problem-focused coping, and a desire for more informal help. Objective need for ICC (normative need), which was related to a higher burden of care, less experienced benefits, and negative relationship quality, was reported by 21.4% of CGs. According to a sensitivity analysis, higher education, a desire for informal help, and living in separate households also predicted a normative need for counseling.

DISCUSSION: Current utilization is significantly lower than the subjectively perceived and objectively existing need for ICC. The identified predictors provide initial strategies for motivating more CGs to use ICC.}, } @article {pmid36011633, year = {2022}, author = {Taylor, BM and Ash, M and King, LP}, title = {Initially High Correlation between Air Pollution and COVID-19 Mortality Declined to Zero as the Pandemic Progressed: There Is No Evidence for a Causal Link between Air Pollution and COVID-19 Vulnerability.}, journal = {International journal of environmental research and public health}, volume = {19}, number = {16}, pages = {}, pmid = {36011633}, issn = {1660-4601}, mesh = {*Air Pollutants/adverse effects/analysis ; *Air Pollution/adverse effects/analysis ; *COVID-19/epidemiology ; Environmental Exposure/analysis ; Humans ; Pandemics ; Particulate Matter/analysis ; }, abstract = {Wu et al. found a strong positive association between cumulative daily county-level COVID-19 mortality and long-term average PM2.5 concentrations for data up until September 2020. We replicated the results of Wu et al. and extended the analysis up until May 2022. The association between PM2.5 concentration and cumulative COVID-19 mortality fell sharply after September 2020. Using the data available from Wu et al.'s "updated_data" branch up until May 2022, we found that the effect of a 1 μg/m[3] increase in PM2.5 was associated with only a +0.603% mortality difference. The 95% CI of this difference was between -0.560% and +1.78%, narrow bounds that include zero, with the upper bound far below the Wu et al. estimate. Short-term trends in the initial spread of COVID-19, not a long-term epidemiologic association, caused an early correlation between air pollution and COVID-19 mortality.}, } @article {pmid36011522, year = {2022}, author = {Sasaki, N and Inoue, A and Asaoka, H and Sekiya, Y and Nishi, D and Tsutsumi, A and Imamura, K}, title = {The Survey Measure of Psychological Safety and Its Association with Mental Health and Job Performance: A Validation Study and Cross-Sectional Analysis.}, journal = {International journal of environmental research and public health}, volume = {19}, number = {16}, pages = {}, pmid = {36011522}, issn = {1660-4601}, mesh = {Cross-Sectional Studies ; Factor Analysis, Statistical ; Humans ; *Mental Health ; Psychometrics ; Reproducibility of Results ; Surveys and Questionnaires ; }, abstract = {OBJECTIVES: This study validated the Japanese version of O'Donovan et al.'s (2020) composite measure of the psychological safety scale and examined the associations of psychological safety with mental health and job-related outcomes.

METHODS: Online surveys were administered twice to Japanese employees in teams of more than three members. Internal consistency and test-retest reliability were tested using Cronbach's α and intra-class correlation coefficient (ICC), respectively. Structural validity was examined using confirmatory factor analysis (CFA) and exploratory factor analysis (EFA). Convergent validity was tested using Pearson's correlation coefficients. Multiple linear regression analyses were conducted to examine the relationship between psychological safety and psychological distress, work engagement, job performance, and job satisfaction.

RESULTS: Two hundred healthcare workers and 200 non-healthcare workers were analyzed. Internal consistency, test-retest reliability, and convergent validity were acceptable. CFA demonstrated poor fit, and EFA yielded a two-factor structure, with team leader as one factor and peers and team forming the second factor. The total score showed significant and expected associations with all outcomes in the adjusted model for all workers.

CONCLUSIONS: The Japanese version of the measure of the psychological safety scale presented good reliability and validity. Psychological safety is important for employees' mental health and performance.}, } @article {pmid36007374, year = {2022}, author = {Ruiz Pardo, AC and Minda, JP}, title = {Reexamining the "brain drain" effect: A replication of Ward et al. (2017).}, journal = {Acta psychologica}, volume = {230}, number = {}, pages = {103717}, doi = {10.1016/j.actpsy.2022.103717}, pmid = {36007374}, issn = {1873-6297}, mesh = {Humans ; *Attention ; *Smartphone ; }, abstract = {The present study was a pre-registered direct replication of Ward et al.'s (2017) second experiment (OSF pre-registration found at: https://osf.io/5fq4r). This replication assigned both smartphone location (on desk, in pocket/bag, or outside of the testing room) and smartphone power (on, or off) for a total of six conditions. Participants completed an automated operation span (OSpan) task, a Cue-Dependent Go/No-Go task, and the smartphone attachment and dependency inventory. It was hypothesized that performance on an attention-demanding task (i.e., the OSpan task) would be worse for those in closer proximity to their smartphone (on desk) and that those with greater smartphone attachment and dependency would have a larger "brain drain" effect. Using the same tasks and conditions as in Ward et al.'s (2017) second experiment, the present study found that the "brain drain" effect did not replicate: there was no difference between smartphone location conditions on performance on either the o-span task or the go/no-go task. These findings demonstrate that the mere presence of one's smartphone may not be enough to affect cognitive performance. Understanding these effects is crucial in a time where smartphones are a basic necessity.}, } @article {pmid36005163, year = {2022}, author = {Kraut, R and Manca, D and Lofters, A and Babenko, O}, title = {A Case for Offering HPV Self-Sampling to Well-Screened Women. Comment on Lesack et al. Willingness to Self-Collect a Sample for HPV-Based Cervical Cancer Screening in a Well-Screened Cohort: HPV FOCAL Survey Results. Curr. Oncol. 2022, 29, 3860-3869.}, journal = {Current oncology (Toronto, Ont.)}, volume = {29}, number = {8}, pages = {5368-5369}, pmid = {36005163}, issn = {1718-7729}, mesh = {Alberta ; *Alphapapillomavirus ; Cross-Sectional Studies ; Early Detection of Cancer/methods ; Female ; Humans ; Papillomaviridae ; *Papillomavirus Infections/diagnosis ; Self Care/methods ; *Uterine Cervical Neoplasms/diagnosis/prevention & control ; Vaginal Smears/methods ; }, abstract = {Lesack et al. recently published a cross-sectional study that focused on human papillomavirus (HPV) self-sampling in the screened population, a population not conventionally thought of for HPV self-sampling. They found 52% of well-screened, highly educated women who participated in the Human Papillomavirus For Cervical Cancer (HPV FOCAL) screening trial in British Columbia, Canada, would be willing to self-collect an HPV sample. We published a similar study in 2021 on well-screened, highly educated women affiliated with a family medicine clinic in Edmonton, Alberta, Canada, and found that 60% of these women preferred to have the option of HPV self-sampling. Our findings reinforce Lesack et al.'s results and together provide evidence for offering HPV self-sampling as an option for the well-screened population.}, } @article {pmid35998315, year = {2023}, author = {Zhang, X and Zhang, Y and Zhang, W and Zhang, M}, title = {Comment on Rie Tanaka et al.'s "Diagnosis of Vitreoretinal Lymphoma Using a Combination of Diagnostic Test Results".}, journal = {Ocular immunology and inflammation}, volume = {31}, number = {5}, pages = {1111}, doi = {10.1080/09273948.2022.2108463}, pmid = {35998315}, issn = {1744-5078}, mesh = {Humans ; *Retinal Neoplasms/diagnosis/pathology ; Vitreous Body/pathology ; *Eye Neoplasms/diagnosis ; *Lymphoma, Non-Hodgkin/pathology ; Diagnostic Tests, Routine ; }, } @article {pmid35993352, year = {2023}, author = {Capraro, V and Celadin, T}, title = {"I Think This News Is Accurate": Endorsing Accuracy Decreases the Sharing of Fake News and Increases the Sharing of Real News.}, journal = {Personality & social psychology bulletin}, volume = {49}, number = {12}, pages = {1635-1645}, pmid = {35993352}, issn = {1552-7433}, mesh = {Humans ; *Disinformation ; *Heuristics ; }, abstract = {Accuracy prompts, nudges that make accuracy salient, typically decrease the sharing of fake news, while having little effect on real news. Here, we introduce a new accuracy prompt that is more effective than previous prompts, because it does not only reduce fake news sharing, but it also increases real news sharing. We report four preregistered studies showing that an "endorsing accuracy" prompt ("I think this news is accurate"), placed into the sharing button, decreases fake news sharing, increases real news sharing, and keeps overall engagement constant. We also explore the mechanism through which the intervention works. The key results are specific to endorsing accuracy, rather than accuracy salience, and endorsing accuracy does not simply make participants apply a "source heuristic." Finally, we use Pennycook et al.'s limited-attention model to argue that endorsing accuracy may work by making people more carefully consider their sharing decisions.}, } @article {pmid35967828, year = {2023}, author = {Torrington, J and Bower, M and Burns, EC}, title = {What self-regulation strategies do elementary students utilize while learning online?.}, journal = {Education and information technologies}, volume = {28}, number = {2}, pages = {1735-1762}, pmid = {35967828}, issn = {1360-2357}, abstract = {Little is known about the strategies elementary school students use to self-regulate their learning while in a hypermedia environment. This exploratory study investigated the self-regulatory strategies that young students (N = 48, M age = 10.75) utilized while individually completing a 20-min online research task about space. Video data was coded using Azevedo et al.'s (2004) established coding scheme for analyzing self-regulatory behavior in hypermedia environments. Results showed that young students spent the majority of their time using cognitive strategies (M = 75.26%) to read and summarise information to complete the task. Little time was taken to plan (M = 6.99%) or monitor (M = 5.92%) their work or learning processes, which are key attributes of effective self-regulation. The study reveals the disparity between the ability to navigate within a hypermedia environment and utilizing planning and monitoring processes to enhance learning while using digital tools. This study highlights the need for the explicit teaching of planning and monitoring strategies in order for young students to develop the full range of self-regulation skills they need when using technology, for instance while learning from home during COVID-19. Implications for curriculum policy and teacher practice are discussed.}, } @article {pmid35965311, year = {2022}, author = {Manero, AC and McLinden, SL and Sparkman, J and Oskarsson, B}, title = {Evaluating surface EMG control of motorized wheelchairs for amyotrophic lateral sclerosis patients.}, journal = {Journal of neuroengineering and rehabilitation}, volume = {19}, number = {1}, pages = {88}, pmid = {35965311}, issn = {1743-0003}, mesh = {Aged ; *Amyotrophic Lateral Sclerosis ; Electromyography ; Feedback ; Female ; Humans ; Male ; Middle Aged ; *Wheelchairs ; }, abstract = {BACKGROUND: This study evaluated a novel control method for patients unable to independently control powered wheelchairs. Patients with amyotrophic lateral sclerosis often require a wheelchair but struggle with sufficient hand dexterity required for joystick control making them a population that needs this type of control method.

METHODS: The study employed a novel control mechanism, using electromyography surface sensors applied to temporalis muscles able to measure the myoelectric voltage. Pattern and magnitude control of muscle contraction allowed for steering intention recognition and were used to manipulate their power wheelchair joystick. Four patients ages 51 to 69, two female and two male with amyotrophic lateral sclerosis, conducted Wheelchair Skills Test developed by Dalhousie University and were surveyed on the experience's Clinical Global Impression of Change.

RESULTS: Findings showed independent steering was capable for patients without hand function and provided recommendations for improved human-machine interface. All patients demonstrated the ability to engage the system, with varying precision, for driving their wheelchair in a controlled environment.

CONCLUSIONS: Three patients in the pilot trial reported the highest score of clinical global impression of change, all of whom had lost independent control of their wheelchair joystick. Patient four retained impaired hand dexterity for joystick control and reported negative impression of change, comparatively. Feedback from the study will be leveraged to improve training outcomes. Trial registration Subjects provided signed informed consent according to the Declaration of Helsinki to enter the study that was approved by the Mayo Clinic Institutional Review Board in Rochester, Minnesota. The study is registered on ClinicalTrials.gov under identifier NCT04800926 as of March 14, 2021 retrospectively registered.}, } @article {pmid35964088, year = {2022}, author = {Nam, JY}, title = {Comparison of global indicators for severe maternal morbidity among South Korean women who delivered from 2003 to 2018: a population-based retrospective cohort study.}, journal = {Reproductive health}, volume = {19}, number = {1}, pages = {177}, pmid = {35964088}, issn = {1742-4755}, mesh = {Cohort Studies ; Female ; Humans ; Maternal Age ; Pregnancy ; *Pregnancy Complications/epidemiology ; *Prenatal Care ; Retrospective Studies ; }, abstract = {BACKGROUND: Even though several severe maternal morbidity (SMM) indicators exist globally, indicators that can serve as international standards are needed. Therefore, this study aimed to compare the SMM risk assessment using four international indicators and identify the factors underlying the differences among the risk assessments obtained by the various indicators.

METHODS: This study used the National Health Insurance delivery cohort in South Korea from 2003 to 2018. SMM was estimated using four indicators: the United States Centers for Disease Control and Prevention (US-CDC) SMM algorithm, the American College of Obstetricians and Gynecologists (ACOG) gold standard guidelines, Zwart et al.'s indicators for the Netherlands, and the European Network on Severe Acute Maternal Morbidity (EURONET-SAMM) index. Generalized estimating equations models were used to identify the relationships between SMM indicators and risk factors.

RESULTS: The SMM incidence rates in 6,421,091 deliveries, were 2.36%, 3.12%, 0.31%, and 1.36% using the US-CDC, ACOG, Zwart et al.'s, and EURONET SAMM indicators, respectively. In sub indicators, hemorrhage-related codes constituted the highest proportion of all SMM indicators. Advanced maternal age was related to high risk in all four SMM indicators (US-CDC: 40-44 years, RR 1.67, 95% CI 1.63-1.71; ACOG's guidelines: 40-44 years, RR 1.52, 95% CI 1.49-1.56; Zwart's indicators: RR 2.72, 95% CI 2.55-2.90; EURONET-SAMM: RR 2.04, 95% CI 1.97-2.11) compared to those aged 25-29 years. In residential area, women who lived in rural area had approximately 1.2- to 1.5-fold higher risk of SMM compared to those who lived in Seoul. Additionally, inadequate prenatal care was associated with a 1.1- to 1.4-fold higher risk of SMM compared to adequate prenatal care.

CONCLUSIONS: SMM was associated with maternal age, socioeconomic status, and adverse obstetric factors using various international SMM indicators. Further studies are needed to further determine risk and preventable factors for SMM and to identify more specific causes associated with the frequent sub-indicators of SMM.}, } @article {pmid35962857, year = {2022}, author = {Piozzi, GN and Khobragade, K and Kim, SH}, title = {Comment on Palmeri et al.'s (2022) pattern of recurrence and survival after D2 right colectomy for cancer: is there place for a routine more extended lymphadenectomy?.}, journal = {Updates in surgery}, volume = {74}, number = {5}, pages = {1791-1792}, pmid = {35962857}, issn = {2038-3312}, mesh = {Colectomy ; Humans ; *Lymph Node Excision ; *Neoplasms ; }, } @article {pmid35953813, year = {2022}, author = {Mang, JM and Seuchter, SA and Gulden, C and Schild, S and Kraska, D and Prokosch, HU and Kapsner, LA}, title = {DQAgui: a graphical user interface for the MIRACUM data quality assessment tool.}, journal = {BMC medical informatics and decision making}, volume = {22}, number = {1}, pages = {213}, pmid = {35953813}, issn = {1472-6947}, mesh = {*Data Accuracy ; Hospitals, University ; Humans ; *Software ; User-Computer Interface ; }, abstract = {BACKGROUND: With the growing impact of observational research studies, there is also a growing focus on data quality (DQ). As opposed to experimental study designs, observational research studies are performed using data mostly collected in a non-research context (secondary use). Depending on the number of data elements to be analyzed, DQ reports of data stored within research networks can grow very large. They might be cumbersome to read and important information could be overseen quickly. To address this issue, a DQ assessment (DQA) tool with a graphical user interface (GUI) was developed and provided as a web application.

METHODS: The aim was to provide an easy-to-use interface for users without prior programming knowledge to carry out DQ checks and to present the results in a clearly structured way. This interface serves as a starting point for a more detailed investigation of possible DQ irregularities. A user-centered development process ensured the practical feasibility of the interactive GUI. The interface was implemented in the R programming language and aligned to Kahn et al.'s DQ categories conformance, completeness and plausibility.

RESULTS: With DQAgui, an R package with a web-app frontend for DQ assessment was developed. The GUI allows users to perform DQ analyses of tabular data sets and to systematically evaluate the results. During the development of the GUI, additional features were implemented, such as analyzing a subset of the data by defining time periods and restricting the analyses to certain data elements.

CONCLUSIONS: As part of the MIRACUM project, DQAgui is now being used at ten German university hospitals for DQ assessment and to provide a central overview of the availability of important data elements in a datamap over 2 years. Future development efforts should focus on design optimization and include a usability evaluation.}, } @article {pmid35929650, year = {2022}, author = {Mundie, C and Donelle, L}, title = {Health activism as nursing practice: A scoping review.}, journal = {Journal of advanced nursing}, volume = {78}, number = {11}, pages = {3607-3617}, doi = {10.1111/jan.15399}, pmid = {35929650}, issn = {1365-2648}, mesh = {Humans ; *Nurse's Role ; }, abstract = {AIMS: The aim was to assess the current literature investigating health activism within nursing practice.

DESIGN: This was a scoping review of the literature utilizing the updated Levac et al.'s framework.

DATA SOURCE/REVIEW METHODS: A search of the CINAHL, PubMed, Scopus and Allied Health databases was conducted for peer-reviewed, English research published between January 2000 and April 2021.

RESULTS: Thirty-one articles met the criteria for inclusion in this study. The included research in nursing and health activism was heterogeneous in topic and method and primarily conducted in North America. Four themes resulted from the inductive thematic analysis: (1) Doing Health Activism, (2) Facilitators to Engaging in Health Activism, (3) Barriers to Health Activism Engagement and (4) Limited Education. Activism was not consistently defined and the term was used interchangeably with advocacy.

CONCLUSION: There is a gap between nursing scope of practice, and education and skills in health activism. There is limited research regarding health activism and what constitutes as health activism. There is an opportunity to improve health activism awareness and skills within the nursing profession and undergraduate education and to produce nursing research on health activism.

IMPACT: Health activism is integral to the nursing role, however, evidence suggests nurses lack confidence to engage in activism as practice. This is important for nurses across the world and in all care specialities.}, } @article {pmid35925916, year = {2022}, author = {Park, JW and Yea, JW and Park, J and Oh, SA}, title = {Setup uncertainties and appropriate setup margins in the head-tilted supine position of whole-brain radiotherapy (WBRT).}, journal = {PloS one}, volume = {17}, number = {8}, pages = {e0271077}, pmid = {35925916}, issn = {1932-6203}, mesh = {Brain ; Cone-Beam Computed Tomography/methods ; Humans ; *Radiotherapy Planning, Computer-Assisted/methods ; Radiotherapy Setup Errors/prevention & control ; *Radiotherapy, Image-Guided/methods ; Supine Position ; }, abstract = {Various applications of head-tilting techniques in whole-brain radiotherapy (WBRT) have been introduced. However, a study on the setup uncertainties and margins in head-tilting techniques has not been reported. This study evaluated the setup uncertainties and determined the appropriate planning target volume (PTV) margins for patients treated in the head-tilted supine (ht-SP) and conventional supine position (c-SP) in WBRT. Thirty patients who received WBRT at our institution between October 2020 and May 2021 in the c-SP and ht-SP were investigated. The DUON head mask (60124, Orfit Industries, Wijnegem, Belgium) was used in the c-SP, and a thermoplastic U-Frame Mask (R420U, Klarity Medical & Equipment Co. Ltd., Lan Yu, China) was used in the ht-SP. Daily setup verification using planning computed tomography (CT) and cone-beam CT was corrected for translational (lateral, longitudinal, and vertical) and rotational (yaw) errors. In the c-SP, the means of systematic errors were -0.80, 0.79, and 0.37 mm and random errors were 0.27, 0.54, and 0.39 mm in the lateral, longitudinal, and vertical translational dimensions, respectively. Whereas, for the ht-SP, the means of systematic errors were -0.07, 0.73, and -0.63 mm, and random errors were 0.75, 1.39, 1.02 mm in the lateral, longitudinal, and vertical translational dimensions, respectively. The PTV margins were calculated using Stroom et al.'s [2Σ+0.7σ] and van Herk et al.'s recipe [2.5Σ+0.7σ]. Appropriate PTV margins with van Herk et al.'s recipe in WBRT were <2 mm and 1.5° in the c-SP and <3 mm and 2° in the ht-SP in the translational and rotational directions, respectively. Although the head tilt in the supine position requires more margin, it can be applied as a sufficiently stable and effective position in radiotherapy.}, } @article {pmid35919096, year = {2022}, author = {Ogihara, Y}, title = {Ethnic differences in names in China: A comparison between Chinese Mongolian and Han Chinese cultures in Inner Mongolia.}, journal = {F1000Research}, volume = {11}, number = {}, pages = {55}, pmid = {35919096}, issn = {2046-1402}, mesh = {*Asian People ; China ; Humans ; }, abstract = {I propose two suggestions on Stojcic et al.'s (2020) Study 3, which examined ethnic differences in individualism between Chinese Mongolian and Han Chinese cultures in China. The authors analyzed the names of all residents in the Inner Mongolia Autonomous Region of China and found that the percentages of common names among Chinese Mongolians were smaller than those among Han Chinese. The authors concluded that Chinese Mongolians are more independent than Han Chinese. However, two questions remain unanswered. First, although the authors analyzed the names of people in all age groups together and did not analyze the names by birth year, how was the effect of time controlled? Second, although the authors treated name indices, which have been used as group-level indicators in previous research, as individual-level indicators, how did the authors confirm whether name indices can be used as individual-level indicators? Addressing these two questions would contribute to a better understanding of ethnic differences in individualism in China.}, } @article {pmid35916954, year = {2022}, author = {Larrague, C and Fieiras, C and Campelo, D and Comba, FM and Zanotti, G and Slullitel, PA and Buttaro, MA}, title = {Feasibility of total hip arthroplasty in cerebral palsy patients: a systematic review on clinical outcomes and complications.}, journal = {International orthopaedics}, volume = {46}, number = {11}, pages = {2493-2507}, pmid = {35916954}, issn = {1432-5195}, mesh = {Humans ; *Arthroplasty, Replacement, Hip/adverse effects/methods ; *Cerebral Palsy/complications/surgery ; Feasibility Studies ; *Hip Prosthesis/adverse effects ; Prospective Studies ; Prosthesis Failure ; Reoperation/adverse effects ; Retrospective Studies ; }, abstract = {PURPOSE: Total hip arthroplasty (THA) is a successful treatment for hip osteoarthritis secondary to hip dysplasia. However, the reported rate of complications following THA in the settings of neuromuscular diseases is high. This systematic review aimed to analyze the indications, functional outcomes and surgical failures of primary THA in cerebral palsy (CP) patients.

METHODS: MEDLINE, EMBASE and the Cochrane Database of Systematic Reviews were searched, and all clinical studies focusing on THA in patients with CP from inception through March 2020 were included. The methodological quality was assessed with Guo et al.'s quality appraisal checklist for case series and case-control studies, while cohort and prospective studies were evaluated with a modified version of the Downs and Black's quality assessment checklist.

RESULTS: The initial search returned 69 studies out of which 15, including 2732 THAs, met the inclusion criteria. The most frequent indication for THA was dislocated painful hip for which previous non-operative treatment had failed. Complications presented in 10 to 45% of cases. The most frequently reported complication was dislocation (1-20%), followed by component loosening (0.74-20%). Aseptic component loosening was the most frequent cause of revision surgery, followed by dislocation and periprosthetic fracture. Mean implant survival at ten years was 84% (range 81-86%).

CONCLUSION: The available literature suggests that although THA is a beneficial procedure in CP patients, it has a higher rate of complications and worse implant survival than the general population.}, } @article {pmid35910916, year = {2022}, author = {Infante, C and Vieitez-Martinez, I and Rodríguez-Chávez, C and Nápoles, G and Larrea-Schiavon, S and Bojorquez, I}, title = {Access to Health Care for Migrants Along the Mexico-United States Border: Applying a Framework to Assess Barriers to Care in Mexico.}, journal = {Frontiers in public health}, volume = {10}, number = {}, pages = {921417}, pmid = {35910916}, issn = {2296-2565}, mesh = {*COVID-19/epidemiology ; Health Services Accessibility ; Humans ; Mexico ; Pandemics ; Public Policy ; *Transients and Migrants ; United States ; }, abstract = {BACKGROUND: Migrants in Mexico are entitled to care at all levels, independently of their migration status. However, previous studies show that access to care is difficult for this population. As the movement of in-transit migrants and asylum seekers has been interrupted at the Mexico-United States border by migration policies such as the "Remain in Mexico" program, and by border closures due to the COVID-19 pandemic, the Mexican health system has the challenge of providing them with health care. Levesque et al.'s framework, according to which access occurs at the interface of health system characteristics and potential users' abilities to interact with it, is a useful theoretical tool to analyze the barriers faced by migrants.

OBJECTIVE: The objective of this article is to analyze the barriers to access the public Mexican health system, encountered by migrants in cities in Mexican states at the Mexico-United States border during the COVID-19 pandemic.

METHODS: Data came from a multiple case study of the response of migrant shelters to health care needs during the COVID-19 pandemic. The study consisted of a non-probability survey of migrants with a recent health need, and interviews with persons working in civil society organizations providing services to migrants, governmental actors involved in the response to migration, and academics with expertise in the subject. We analyzed the quantitative and qualitative results according to Levesque et al.'s framework.

RESULTS: 36/189 migrants surveyed had sought health care in a public service. The main limitations to access were in the availability and accommodation dimension (administrative barriers decreasing migrants' ability to reach the system), and the affordability dimension (out-of-pocket costs limiting migrants' ability to pay). Civil society organizations were a major source of social support, helping migrants overcome some of the barriers identified.

CONCLUSIONS: While Mexico's health regulations are inclusive of migrants, in practice there are major barriers to access public health services, which might inhibit migrants from seeking those services. In order to comply with its commitment to guarantee the right to health of all persons, the Mexican health authorities should address the implementation gap between an inclusive policy, and the barriers to access that still remain.}, } @article {pmid35909093, year = {2023}, author = {Callan, A and Corbally, M and McElvaney, R}, title = {A commentary on the challenges for nurses in identifying and responding to intimate partner violence amongst gay and bisexual men.}, journal = {Journal of advanced nursing}, volume = {79}, number = {4}, pages = {e21-e29}, doi = {10.1111/jan.15392}, pmid = {35909093}, issn = {1365-2648}, mesh = {Humans ; Male ; Female ; Homosexuality, Male ; *Sexual and Gender Minorities ; Sexual Behavior ; *Intimate Partner Violence ; *Nurses ; }, abstract = {AIM: This commentary elucidates the challenges for nurses in effectively identifying and supporting gay and bisexual men who experience intimate partner violence and offers guidance for education, training and practice to nurses when responding to patients who may be experiencing intimate partner violence.

DESIGN: The commentary highlights issues raised by Callan et al.'s (2020) scoping review, translating the experiences of male sexual minorities undergoing abuse to a nursing context, in particular, issues such as homophobic remarks and heteronormative practices in health care and nursing-led environments militate against the identification of individuals who may be experiencing coerced sexual risk-taking, homophobia and sexual orientation outing.

RESULTS: Intimate partner violence is a widespread issue that permeates across heterosexual and LGBTQ+ communities, while impressing on the everyday realities of nurses. The potential for discrimination against sexual minority patients may be offset by improving training, education and offering recommendations for nurses in how to identify IPV and how to assess risk.

CONCLUSIONS: Nurses possess essential training and transferable skills such as empathy, adaptability, active listening and diplomacy and are ideally placed to facilitate disclosure of intimate partner violence. Gaps in knowledge, training and organizational support for nurses may be effectively addressed through drawing on extant research and international best practice guidelines.

IMPACT: Suggestions for research, education and practice to identify gay and bisexual male survivors, intervene appropriately and avoid missed disclosure opportunities are made. We conclude with a table of recommendations with a view to enhancing the essential response of nurses in addressing intimate partner violence in marginalized communities.}, } @article {pmid35901113, year = {2022}, author = {Jo, HR and Pak, KS and Kim, CH and Zhang, IJ}, title = {Cryptanalysis and improved mutual authentication key agreement protocol using pseudo-identity.}, journal = {PloS one}, volume = {17}, number = {7}, pages = {e0271817}, pmid = {35901113}, issn = {1932-6203}, mesh = {Algorithms ; Communication ; *Computer Security ; Confidentiality ; Humans ; Logic ; *Telemedicine ; }, abstract = {The authentication key agreement is a scheme that generates a session key for encrypted communication between two participants. In the authentication key agreement, to provide the mutual authentication and the robust session key agreement is one of the important security requirements to enhance the security performance of key agreement. Recently Zhou et al. had proposed the key agreement protocol using pseudo-identifiers, but we found that there were weaknesses in their protocol. We have demonstrated that Zhou et al.'s protocol is vulnerable to replay attack, fails to provide mutual authentication, no key control, re-registration with the original identifier and efficiency in the verification of wrong password. We improved their scheme and proposed an improved authentication key agreement protocol that provides robust mutual authentication and the secure session key agreement. We analyzed its security performance using BAN logic and AVISPA tools and compared computational cost, communication overhead and security properties with other related schemes.}, } @article {pmid35895617, year = {2022}, author = {Xiao, LY}, title = {Reserve your judgment on "Draconian" Chinese video gaming restrictions on children •.}, journal = {Journal of behavioral addictions}, volume = {11}, number = {2}, pages = {249-255}, pmid = {35895617}, issn = {2063-5303}, mesh = {Adolescent ; *Behavior, Addictive ; Child ; China ; *Gambling ; Humans ; Judgment ; *Video Games ; }, abstract = {China imposed strict restrictions on young people's participation in videogaming from September 2021. Colder Carras et al.'s commentary (2021) referred to this policy as 'draconian,' i.e., 'excessively harsh and severe.' However, any opinion on whether this policy is 'draconian' is a value judgment, and any judgment on its 'effectiveness' ought to be reserved until proven or disproven by empirical evidence. Indeed, the Chinese policy is neither potentially ineffective nor draconian, and is already providing at least one identifiable benefit: enhancing consumer protection by effectively reducing underage players' monetary spending on videogames, including on randomised, gambling-like mechanics known as 'loot boxes.'}, } @article {pmid35895607, year = {2022}, author = {Szabo, A and Dinardi, JS and Egorov, AY}, title = {Apples and oranges in the basket of a clinical model for exercise addiction: Rebuttal to Brevers et al. (2022).}, journal = {Journal of behavioral addictions}, volume = {11}, number = {2}, pages = {240-242}, pmid = {35895607}, issn = {2063-5303}, mesh = {*Exercise ; Humans ; }, abstract = {This note is a reply to Brevers et al.'s (2022) the commentary. We first explain that the commentary's title is in discord with the theoretical implications of the Expanded Interactional Model of Exercise Addiction (EIMEA; Dinardi et al., 2021). Subsequently, we argue that in contrast to Brevers et al.'s arguments, exercise volume or intensive physical exercise is not even mentioned in the revised EIMEA. Most importantly, we point out that the commentary's reference to assessment scales of exercise addiction is irrelevant, because the EIMEA is intended for idiographic clinical cases rather than nomothetic research. Furthermore, we discuss how the ELMEA cannot account for secondary exercise addiction and motivational incentives due to its individual-specific orientation. Finally, we conclude our reply by highlighting that Brevers et al.'s commentary seems to revolve around nomothetic research assessing a certain level of 'risk' of exercise addiction, while the EIMEA accounts for specific clinically dysfunctional cases presented in the limited number of case studies published in the literature.}, } @article {pmid35894384, year = {2022}, author = {de Assis, LVM and Harder, L and Lacerda, JT and Parsons, R and Kaehler, M and Cascorbi, I and Nagel, I and Rawashdeh, O and Mittag, J and Oster, H}, title = {Rewiring of liver diurnal transcriptome rhythms by triiodothyronine (T3) supplementation.}, journal = {eLife}, volume = {11}, number = {}, pages = {}, pmid = {35894384}, issn = {2050-084X}, mesh = {Animals ; *Circadian Clocks/genetics ; *Circadian Rhythm/genetics ; Dietary Supplements ; Gene Expression Regulation ; Lipids ; Liver/metabolism ; Mice ; Transcriptome ; Triiodothyronine/genetics/metabolism ; Xenobiotics/metabolism ; }, abstract = {Diurnal (i.e., 24 hr) physiological rhythms depend on transcriptional programs controlled by a set of circadian clock genes/proteins. Systemic factors like humoral and neuronal signals, oscillations in body temperature, and food intake align physiological circadian rhythms with external time. Thyroid hormones (THs) are major regulators of circadian clock target processes such as energy metabolism, but little is known about how fluctuations in TH levels affect the circadian coordination of tissue physiology. In this study, a high triiodothyronine (T3) state was induced in mice by supplementing T3 in the drinking water, which affected body temperature, and oxygen consumption in a time-of-day-dependent manner. A 24-hr transcriptome profiling of liver tissue identified 37 robustly and time independently T3-associated transcripts as potential TH state markers in the liver. Such genes participated in xenobiotic transport, lipid and xenobiotic metabolism. We also identified 10-15% of the liver transcriptome as rhythmic in control and T3 groups, but only 4% of the liver transcriptome (1033 genes) were rhythmic across both conditions - amongst these, several core clock genes. In-depth rhythm analyses showed that most changes in transcript rhythms were related to mesor (50%), followed by amplitude (10%), and phase (10%). Gene set enrichment analysis revealed TH state-dependent reorganization of metabolic processes such as lipid and glucose metabolism. At high T3 levels, we observed weakening or loss of rhythmicity for transcripts associated with glucose and fatty acid metabolism, suggesting increased hepatic energy turnover. In summary, we provide evidence that tonic changes in T3 levels restructure the diurnal liver metabolic transcriptome independent of local molecular circadian clocks.}, } @article {pmid35882744, year = {2023}, author = {Tom, MA and Edson, TC and Louderback, ER and Nelson, SE and Amichia, KA and LaPlante, DA}, title = {Second Session at the Virtual Poker Table: A Contemporary Study of Actual Online Poker Activity.}, journal = {Journal of gambling studies}, volume = {39}, number = {3}, pages = {1295-1317}, pmid = {35882744}, issn = {1573-3602}, mesh = {Humans ; *Gambling/psychology ; Antisocial Personality Disorder ; Electronics ; Internet ; }, abstract = {Technological advancements and worldwide television exposure led to a poker boom in the early 2000s, and poker (both live and online) has retained some of that popularity today. The present study examined online poker playing trends based on actual electronic betting records data for 2489 subscribers to a major global internet gambling operator from 2015 to 2017. We found that overall financial involvement (median total overall spend: €439.7) and time commitment (median number of sessions: 43) during the two-year study period were relatively moderate. We identified the top 1% by total overall spend as a subgroup of highly involved players with disproportionately higher financial involvement (median total overall spend: €272,581.4) and time commitment (median number of sessions: 1149). Our results were similar to those reported in LaPlante et al.'s (Comput Hum Behav 25(3):711-717, 2009. https://doi.org/10.1016/j.chb.2008.12.027) study of online poker betting records, suggesting that players' levels of involvement are similar to those from ten years ago despite numerous changes to the online poker environment. We also analyzed records of deposits and withdrawals, and we observed similar indicators of moderate gambling behavior within the overall sample (median two-year total amount deposited: €176.4). In contrast to popular beliefs about internet gambling, in our sample, most online poker play was arguably moderate. However, a small percentage of highly involved players play poker at extreme levels and require closer scrutiny.}, } @article {pmid35882374, year = {2022}, author = {Brewin, CR and Miller, JK and Burchell, B}, title = {Estimating the total prevalence of PTSD among the UK police force: Formal comment on Stevelink et al. (2020).}, journal = {PloS one}, volume = {17}, number = {5}, pages = {e0268621}, pmid = {35882374}, issn = {1932-6203}, mesh = {Diagnostic and Statistical Manual of Mental Disorders ; Humans ; Police ; Prevalence ; *Stress Disorders, Post-Traumatic/epidemiology ; United Kingdom/epidemiology ; }, abstract = {Two recent surveys have reported widely differing prevalence rates for posttraumatic stress disorder (PTSD) within the U.K. police force. Stevelink et al. (2020) reported a rate of 3.9% whereas a survey conducted for the charity Police Care UK reported a rate of 20.6%. In this comment we discuss how definitions and methodological factors can impact prevalence rates. We consider a number of possible reasons for the discrepancy between the surveys, and conclude that it is most likely a method artefact. Stevelink et al.'s survey reported the prevalence of recent-onset DSM-IV PTSD only, whereas the Police Care UK survey reported the total ICD-11 PTSD and Complex PTSD prevalence, regardless of when in the person's career the traumatic events occurred. Analysing the Police Care UK data using Stevelink et al.'s procedures produced practically identical prevalence rates, suggesting that the discrepancy was apparent rather than real.}, } @article {pmid35881109, year = {2023}, author = {Kim, JL and Lewallen, KM and Hollingsworth, EK and Shah, AS and Simmons, SF and Vasilevskis, EE}, title = {Patient-Reported Barriers and Enablers to Deprescribing Recommendations During a Clinical Trial (Shed-MEDS).}, journal = {The Gerontologist}, volume = {63}, number = {3}, pages = {523-533}, pmid = {35881109}, issn = {1758-5341}, support = {I01 HX002441/HX/HSRD VA/United States ; R01 AG053264/AG/NIA NIH HHS/United States ; UL1 TR000445/TR/NCATS NIH HHS/United States ; }, mesh = {Humans ; Aged ; *Deprescriptions ; Patient Discharge ; Decision Making, Shared ; Dissent and Disputes ; Patient Reported Outcome Measures ; }, abstract = {BACKGROUND AND OBJECTIVES: Effective deprescribing requires shared decision making between a patient and their clinician, and should be used when implementing evidence-based deprescribing conversations. As part of the Shed-MEDS clinical trial, this study assessed barriers and enablers that influence patient decision making in deprescribing to inform future implementation efforts and adaptations.

RESEARCH DESIGN AND METHODS: Shed-MEDS, a randomized controlled deprescribing trial, included hospitalized older adults discharging to post-acute care facilities. A trained clinician reviewed each participant's medical history and medication list to identify medications with potential for deprescribing. The study clinician then conducted a semistructured patient-centered deprescribing interview to determine patient (or surrogate) concerns about medications and willingness to deprescribe. Reeve et al.'s (2013) framework was used to categorize barriers and enablers to deprescribing from the patient's perspective, including "appropriateness of cessation," "fear," "dislike of a medication," "influences," and "process of cessation."

RESULTS: Overall, participants/surrogates (N = 177) agreed with 63% (883 total medications) of the study clinician's deprescribing recommendations. Thematic analysis revealed that "appropriateness" of a medication was the most common barrier (88.2%) and enabler (67.3%) to deprescribing. Other deprescribing enablers were in the following domains: "influences" (22.7%), "process" (22.5%), "pragmatic" (19.4%), and "dislike" (5.3%).

DISCUSSION AND IMPLICATIONS: Use of a semistructured deprescribing interview conversation tool allowed study clinicians to elicit individual barriers and enablers to deprescribing from the patient's perspective. Participants in this study expressed more agreement than disagreement with study clinicians' deprescribing recommendations. These results should inform future implementation efforts that incorporate a patient-centered framework during deprescribing conversations.

NCT02979353.}, } @article {pmid35875962, year = {2022}, author = {Bleske-Rechek, A and Deaner, RO}, title = {Societies also prioritize female survival.}, journal = {The Behavioral and brain sciences}, volume = {45}, number = {}, pages = {e131}, doi = {10.1017/S0140525X22000528}, pmid = {35875962}, issn = {1469-1825}, mesh = {*Attitude ; Female ; Humans ; Male ; *Reproduction ; }, abstract = {We extend Benenson et al.'s hypothesis from the individual level to the societal level. Because women have highly limited reproductive rates, societies have generally prioritized female survival and regarded males as expendable. We describe various lines of evidence that are consistent with this hypothesis, and we offer additional predictions about differential attitudes toward male versus female endangerment.}, } @article {pmid35875959, year = {2022}, author = {March, DS and Gaertner, L}, title = {Female advantage in threat avoidance manifests in threat reaction but not threat detection.}, journal = {The Behavioral and brain sciences}, volume = {45}, number = {}, pages = {e142}, doi = {10.1017/S0140525X22000462}, pmid = {35875959}, issn = {1469-1825}, mesh = {*Fear ; Female ; Humans ; Male ; }, abstract = {Threat avoidance involves both detection of a threatening stimulus and reaction to it. We demonstrate with empirically validated stimuli (that are threatening, nonthreatening-negative, neutral, or positive) that threat detection is more pronounced among males, whereas threat reactivity is more pronounced among females. Why women are less efficient detectors of threat challenges Benenson et al.'s conceptual analysis.}, } @article {pmid35875005, year = {2022}, author = {Zhang, Z and Zhu, Y and Wang, Q and Chang, T and Liu, C and Zhu, Y and Wang, X and Cao, X}, title = {Global Trends and Research Hotspots of Exercise for Intervening Diabetes: A Bibliometric Analysis.}, journal = {Frontiers in public health}, volume = {10}, number = {}, pages = {902825}, pmid = {35875005}, issn = {2296-2565}, mesh = {*Bibliometrics ; Cardiorespiratory Fitness ; *Diabetes Mellitus/therapy ; *Exercise ; Glycated Hemoglobin ; Glycemic Control ; Humans ; Hypoglycemic Agents/therapeutic use ; Sedentary Behavior ; }, abstract = {BACKGROUND: Diabetes is a chronic metabolic disease characterized by hyperglycemia that often occurs in adults. Many studies have indicated that exercise is beneficial to the medical management of diabetes. Bibliometric analysis can help investigators to identify the current research concerns to guide future research directions. Nevertheless, the overview bibliometric analysis of this global research topic related to exercise and diabetes is lacking. The present bibliometric study aimed to investigate development trends and research hotspots of exercise and diabetes research and provide researchers with new perspectives in further studies.

MATERIALS AND METHODS: The articles and reviews regarding exercise and diabetes between 2000 and 2020 were retrieved from the Web of Science Core Collection. The scientometrics analytical tool CiteSpace software was used to analyze the cooperation among countries/institutions/journals/authors, analysis of co-occurrence keywords, keywords bursts, and references.

RESULTS: In all, 3,029 peer-reviewed papers were found with a persistently increased tendency over time. The most prolific country and institution were the USA (965) and Univ Alberta (76), respectively. Diabetes Care published most papers (178) and was the most co-cited journal (2,630). Riddell MC had the most publications (53), and Sigal RJ was the most influential author (503 cited times). Colberg et al.'s paper (co-citation counts: 183) showed the strongest citation bursts by the end of 2020, which was the most representative reference. The four research focuses were mellitus, exercise, physical activity, and glycemic control. The two frontiers trends were sedentary behavior and stress. The combination of aerobic and resistance training can effectively improve glycemic control, decrease HbA1c levels, enhance cardiorespiratory fitness, improve lipid levels, and decrease the demand for non-insulin antihyperglycemic agents.

CONCLUSIONS: This study offers a scientific perspective on exercise and diabetes research and provides investigators with valuable information to detect the current research condition, hotspots, and emerging trends for further study.}, } @article {pmid35874363, year = {2022}, author = {Wang, X and He, R}, title = {Supporting Vaccination on TikTok During the COVID-19 Pandemic: Vaccine Beliefs, Emotions, and Comments.}, journal = {Frontiers in psychology}, volume = {13}, number = {}, pages = {938377}, pmid = {35874363}, issn = {1664-1078}, abstract = {TikTok has been one of the most important social media platforms where pandemic-related information converged and has been disseminated. However, how vaccination-related visual content, particularly pro-vaccine videos, influences audiences remains unclear. Using Betsch et al.'s 5C model and Ekman's basic emotion model, we identified 200 trending videos under the hashtag #vaccine on TikTok, and examined the types of vaccine-related beliefs and emotions expressed in videos and the relationship between beliefs, emotions, and supportive comments. Confidence and joy were the most frequently expressed belief and emotion, respectively; confidence (B = 14.84, P < 0.05), surprise (B = 11.29, P < 0.05), and sadness (B = 37.49, P < 0.01) predicted the number of supportive comments. This study expands the 5C framework of vaccine hesitancy into the analysis of pro-vaccine content on social media and offers detailed insights into the specific type of beliefs and emotions and their effects. Practical implications regarding how to address vaccine hesitancy are discussed.}, } @article {pmid35858883, year = {2022}, author = {Li, X and Zhao, Y and Zhang, Z and Zheng, T and Li, S and Yang, G and Lu, Y}, title = {Correlations of magnetic resonance imaging classifications with preoperative functions among patients with refractory lateral epicondylitis.}, journal = {BMC musculoskeletal disorders}, volume = {23}, number = {1}, pages = {690}, pmid = {35858883}, issn = {1471-2474}, support = {2020-2-2073//the Capital's Funds for Health Improvement and Research/ ; 2020-2-2073//the Capital's Funds for Health Improvement and Research/ ; 2020-2-2073//the Capital's Funds for Health Improvement and Research/ ; }, mesh = {Adult ; Arthroscopy/methods ; Female ; Humans ; Magnetic Resonance Imaging/methods ; Male ; Middle Aged ; Pain Measurement ; Retrospective Studies ; *Tennis Elbow/diagnostic imaging/surgery ; }, abstract = {BACKGROUND: To evaluate the correlations between three magnetic resonance imaging (MRI) classifications and preoperative function in patients with refractory lateral epicondylitis (LE).

METHODS: We retrospectively reviewed patients with refractory LE who underwent arthroscopic treatment. Signal changes in the origin of the extensor carpi radialis brevis (ERCB) were evaluated based on three different MRI classification systems. Spearman's rank correlation analysis was used to analyse the correlation between each MRI classification and the preoperative functional and visual analogue scale (VAS). The lateral collateral ligament complex (LCL) in all patients was evaluated using both MRI and arthroscopy. The Mann-Whitney U test was used for the comparison of preoperative VAS and all functional scores between patients with refractory LE combined with LCL lesions, and those without.

RESULTS: There were 51 patients diagnosed with refractory LE between June 2014 to December 2020, all of whom were included in this study. The patients included 32 women and 19 men with a mean age of 49.1 ± 7.6 years (range, 39-60 years). The average duration of symptoms was 21.1 ± 21.2 months (range, 6-120 months). The intra-observer agreements for Steinborn et al.'s classification were 77.9%, 76.0%, and 76.7%, respectively. The inter-observer reliabilities of the three classifications were 0.734, 0.751, and 0.726, respectively. The average intra-observer agreement for the diagnosis of abnormal LCL signal was 89.9%, with an overall weighted kappa value of 0.904. The false-positive rate was 50%, and the false-negative rate was 48% for LCL evaluation on MRI. Spearman's rank correlation analysis did not find significant correlation between any of the three MRI classifications and preoperative VAS or any functional scores (all P > 0.05). There were no significant differences in the VAS and functional scores between patients with abnormal LCL signals on MRI and those without LCL lesions (all P > 0.05).

CONCLUSIONS: Preoperative MRI findings in patients with refractory LE cannot reflect the severity of functional deficiency. Preoperative MRI grading of the origin of the ERCB and preoperative MRI for LCL signal change cannot assist the surgical plan for the treatment of patients with refractory LE.}, } @article {pmid35857282, year = {2022}, author = {Saberi, K and Hickok, G}, title = {A critical analysis of Lin et al.'s (2021) failure to observe forward entrainment in pitch discrimination.}, journal = {The European journal of neuroscience}, volume = {56}, number = {8}, pages = {5191-5200}, pmid = {35857282}, issn = {1460-9568}, support = {R01 DC003681/DC/NIDCD NIH HHS/United States ; R01 DC009659/DC/NIDCD NIH HHS/United States ; }, mesh = {Acoustic Stimulation ; *Pitch Discrimination ; }, abstract = {Forward entrainment refers to that part of the entrainment process that outlasts the entraining stimulus. Several studies have demonstrated psychophysical forward entrainment in a pitch-discrimination task. In a recent paper, Lin et al. (2021) challenged these findings by demonstrating that a sequence of 4 entraining pure tones does not affect the ability to determine whether a frequency modulated pulse, presented after termination of the entraining sequence, has swept up or down in frequency. They concluded that rhythmic sequences do not facilitate pitch discrimination. Here, we describe several methodological and stimulus design flaws in Lin et al.'s study that may explain their failure to observe forward entrainment in pitch discrimination.}, } @article {pmid35845094, year = {2022}, author = {Pohl, A and Wong Hearing, T and Franc, A and Sepulchre, P and Scotese, CR}, title = {Dataset of Phanerozoic continental climate and Köppen-Geiger climate classes.}, journal = {Data in brief}, volume = {43}, number = {}, pages = {108424}, pmid = {35845094}, issn = {2352-3409}, abstract = {This article describes a suite of global climate model output files that provide continental climatic conditions (monthly temperatures, precipitation, evaporation, precipitation minus evaporation balance, runoff) together with the calculated Köppen-Geiger climate classes and topography, for 28 evenly spaced time slices through the Phanerozoic (Cambrian to Quaternary, 540 Ma to 0 Ma). Climatic variables were simulated with the Fast Ocean Atmosphere Model (FOAM), using a recent set of open-access continental reconstructions with paleotopography and recent atmospheric CO2 and solar luminosity estimates. FOAM is a general circulation model frequently used in paleoclimate studies, especially in the Palaeozoic. Köppen-Geiger climate classes were calculated based on simulated temperature and precipitation fields using Wong Hearing et al.'s [1] implementation of Peel et al.'s [2] updated classification. This dataset provides a unique window onto changing continental climate throughout the Phanerozoic that accounts for the simultaneous evolution of paleogeography (continental configuration and topography), atmospheric composition and greenhouse gas forcing, and solar luminosity.}, } @article {pmid35838877, year = {2022}, author = {Kant, A and van Hunsel, F}, title = {Authors' Reply to Mungmunpuntipantip et al.'s Comment on "Description of Frequencies of Reported Adverse Events Following Immunization Among Four Different COVID-19 Vaccine Brands".}, journal = {Drug safety}, volume = {45}, number = {8}, pages = {925-926}, pmid = {35838877}, issn = {1179-1942}, mesh = {*COVID-19/prevention & control ; *COVID-19 Vaccines/adverse effects ; Humans ; Immunization ; Vaccination ; }, } @article {pmid35819170, year = {2023}, author = {Zabel, TA and Jones, E and Peterson, RK and Comi-Morog, N and Stephan, C and Milla, K and Pritchard, AE and Jacobson, LA}, title = {Improved parent self-efficacy following pediatric evaluation: Evidence for value of a telemedicine approach in psychological and neuropsychological assessment.}, journal = {The Clinical neuropsychologist}, volume = {37}, number = {6}, pages = {1221-1238}, pmid = {35819170}, issn = {1744-4144}, support = {P50 HD103538/HD/NICHD NIH HHS/United States ; }, mesh = {Humans ; Child ; *Self Efficacy ; Neuropsychological Tests ; *Telemedicine/methods ; Parents ; }, abstract = {Objective: While considerable inquiry is currently underway into the comparability of psychological test results obtained in onsite/in-person settings versus telemedicine settings, there has been less attention given to the comparability of the impact/outcome of the assessment process across settings. The current quality improvement study conceptualized impact/outcome according to the model of Austin et al. and sought to determine whether the prior finding of increased parent self-efficacy following onsite neuropsychological assessment was also observed when psychological and neuropsychological assessment was conducted via a telemedicine modality. Method: In the course of standard care delivery, ratings from Austin et al.'s four parent self-efficacy items were obtained at time 1 prior to patients' assessment visits and then again at time 2 either (1) following their last assessment/feedback visit (the Complete Assessment group; n = 157) or (2) in the middle of the assessment process prior to the last planned visit (the Incomplete Assessment group; n = 117). Results: Analyses revealed significant findings for time and time × group. Parent self-efficacy ratings improved over time in both groups, with significantly higher ratings in the Complete Assessment group at time 2. When compared to reference means from the in-person/onsite Austin et al. study, ratings from the current study found comparable improvement in parent self-efficacy achieved via telemedicine assessment in the Complete Assessment group. Conclusions: These data support the use of telemedicine based psychological and neuropsychological evaluation and provide preliminary evidence that the impact/outcome is comparable with in-person/onsite assessment.}, } @article {pmid35815147, year = {2022}, author = {Oo, TZ and Habók, A}, title = {Reflection-based questioning: Aspects affecting Myanmar students' reading comprehension.}, journal = {Heliyon}, volume = {8}, number = {7}, pages = {e09864}, pmid = {35815147}, issn = {2405-8440}, abstract = {This study aimed to scrutinize the effects of the reflection-based questioning approach (RBQA) on Myanmar students' achievement in English reading comprehension. The RBQA approach covers Oo et al.'s (2021) reflective teaching model for reading comprehension (based on planning, acting, reflecting, and evaluating) in which the teacher uses a questioning strategy (initiate-response-evaluate model). Employing cluster randomized trials, quasi-experimental research was conducted to investigate RBQA's effectiveness in teaching reading comprehension skills to Grade-9 students. The experimental group (N = 228) received the RBQA intervention; the control group (N = 230) did not receive the intervention but was provided with traditional instruction. During RBQA intervention, teachers used the anonymous student questionnaire and observation scheme as effective reflection tools. After a five-week intervention, both groups completed post-tests to assess their achievement. The study findings revealed that teaching with RBQA had a significant positive effect on students' reading comprehension. Therefore, this study is of immense significance to English language teachers and their students.}, } @article {pmid35808492, year = {2022}, author = {Wang, HW and Tsai, CW and Lin, J and Yang, CW}, title = {Authenticated Semi-Quantum Key Distribution Protocol Based on W States.}, journal = {Sensors (Basel, Switzerland)}, volume = {22}, number = {13}, pages = {}, pmid = {35808492}, issn = {1424-8220}, mesh = {*Computers ; }, abstract = {In 2019, Wen et al. proposed authenticated semi-quantum key distribution (ASQKD) for identity and message using the teleportation of W states and GHZ-like states without pre-shared keys. However, the ASQKD protocol presents a vital issue in the teleportation of W states owing to its inappropriate design. Bob recovers the teleported W states without obtaining the position of the corresponding photons and then returns the recovered photons back to Alice. Hence, the teleportation of W states in Wen et al.'s ASQKD protocol was malfunctioning. Moreover, Wen et al.'s ASQKD protocol requires quantum memory, which strongly disobeys the definition of semi-quantum proposed by Boyer et al. Therefore, in this study, we discover the flaws of Wen et al.'s ASQKD protocol and propose an authenticated semi-quantum key distribution protocol. When compared to Wen et al.'s ASQKD protocol, the proposed ASQKD protocol has the following advantages: legal semi-quantum environment (i.e., does not require quantum memory), reduced quantum hardware requirement (i.e., based only on W states), does not involve classical cryptography (i.e., the hash function), and provided 1.6 times higher qubit efficiency.}, } @article {pmid35787112, year = {2022}, author = {Sharp, C}, title = {Fulfilling the promise of the LPF: Comment on Morey et al. (2022).}, journal = {Personality disorders}, volume = {13}, number = {4}, pages = {316-320}, doi = {10.1037/per0000567}, pmid = {35787112}, issn = {1949-2723}, mesh = {Emotions ; Humans ; *Metacognition ; Personality ; *Personality Disorders/diagnosis ; Personality Inventory ; }, abstract = {In this commentary, I highlight a perceived reluctance in Morey et al.'s (2022) contribution to fully commit to a definition of the level of personality functioning (LPF), not as the functional consequence of extreme traits, but as an intrapsychic system that drives trait manifestation. I argue that for the LPF to reach its full potential to innovate the assessment and diagnosis of personality pathology beyond mere signs and symptoms, it is essential to define the LPF as a subjective meaning-making system located in biological systems that support the metacognitive capacities necessary for abstracting a sense of self. This view reflects the idea that personality does not simply describe a person (as traits do) but also captures how a person manages their self in relation to others (as LPF does). It implies a definition of personality that includes structural motivational components that fulfill an intrapsychic, organizing function, acknowledging the fact that traits alone are not enough to fully describe personality. (PsycInfo Database Record (c) 2022 APA, all rights reserved).}, } @article {pmid35780375, year = {2022}, author = {Alauddin, M and Hossain, MZ and Rahman, MM and Roy, MK and Minto, MR and Islam, MA and Islam, MK and Islam, MS and Saha, MK and Mahmud, AA and Siddiquee, TH and Seraji, SI}, title = {Management of Neglected Rupture of Tendoachilles with Long Gap by Flexor Hallucis Longus Tendon Transfer.}, journal = {Mymensingh medical journal : MMJ}, volume = {31}, number = {3}, pages = {861-868}, pmid = {35780375}, issn = {2408-8757}, mesh = {*Achilles Tendon/injuries/surgery ; Adult ; Aged ; Humans ; Middle Aged ; *Plastic Surgery Procedures/methods ; Rupture/surgery ; *Tendon Injuries/surgery ; Tendon Transfer/methods ; Young Adult ; }, abstract = {The tendo achilles is one of most important tendon in human body which often injured through direct trauma or indirect stress on a weakened tendon. Longer the duration after injury the injured parts likely to move apart, fibrosis and degeneration leading to difficulty in repair or reconstruction. Usually a phase of 4 weeks or more without specific treatment is regarded as chronic or neglected rupture. Different authors described many management protocols about the tendo achilles rupture but there is no procedure of choice for neglected rupture with long gap. Prospective case series of 21 patients of neglected tendo achilles rupture with long gap treated with flexor hallucis longus tendon (FHLT) transfer was taken for study from January 2019 to December 2020 in Mymensingh Medical College Hospital, Bangladesh. Average age of patients was 39.47 years with range 22-65 years. Fifteen (15) cases of traumatic rupture in this study with average age 32.66 years and pathologic 6 cases with average age 56.5 years were recorded. We grafted FHLT from channel by incising Henry's knot. Krackow et al.'s technique was followed for tendon mobilization and bone fixation. We made procedure simpler and cheaper; instead of using interference screw the sutured tendon pulled through the heel and anchored over rubber tube or button by Cole method. Post-operative complications were less with one patient with superficial infection which eventually recovered 3 cases of mild pain and 2 cases of numbness. Questionnaire for surgical outcome measure are satisfactory in 19 patients (90.47%). Final follow up AOFAS score at 6 month (91.61±5.41) was highly significant (p<0.001) in comparison to preoperative score (38.71±9.78). These are comparable to other study. Above mentioned scores indicate the reliability of the surgical system. But our study is a prospective case series with minimum cases. To establish the best procedure for neglected tendo achilles rupture with long gap we recommend further study with larger group and Randomized Controlled Trial (RCT) study among different procedure.}, } @article {pmid35779238, year = {2022}, author = {Bhat, A}, title = {Why add motor to the definition of ASD: A response to Bishop et al.'s critique of Bhat (2021).}, journal = {Autism research : official journal of the International Society for Autism Research}, volume = {15}, number = {8}, pages = {1376-1379}, pmid = {35779238}, issn = {1939-3806}, support = {R01 MH125823/MH/NIMH NIH HHS/United States ; 1R01MH125823-02/NH/NIH HHS/United States ; }, mesh = {*Autism Spectrum Disorder/diagnosis ; Humans ; }, } @article {pmid35773133, year = {2022}, author = {Silva, ABJD and Barros, WMA and Silva, BM and de Oliveira Nogueira Souza, V and Lagranha, CJ}, title = {Letter to the editor: Comment on Bouziotis et al.'s (2022) Association of body mass index with COVID-19 related in-hospital death.}, journal = {Clinical nutrition (Edinburgh, Scotland)}, volume = {41}, number = {12}, pages = {3127-3128}, pmid = {35773133}, issn = {1532-1983}, mesh = {Humans ; Body Mass Index ; *COVID-19 ; Hospital Mortality ; }, } @article {pmid35771956, year = {2023}, author = {Preaux, J and Casadesús, M and Bernardo, M}, title = {A Conceptual Model to Evaluate Service Quality of Direct-to-Consumer Telemedicine Consultation from Patient Perspective.}, journal = {Telemedicine journal and e-health : the official journal of the American Telemedicine Association}, volume = {29}, number = {2}, pages = {156-171}, doi = {10.1089/tmj.2022.0089}, pmid = {35771956}, issn = {1556-3669}, mesh = {Humans ; *Telemedicine ; Delivery of Health Care ; Referral and Consultation ; }, abstract = {Objective and Background: This research aims to develop a theoretical service quality (SQ) model for direct-to-consumer (DTC) telemedicine consultations. Although it can change care delivery for the better, it is crucial to create the appropriate measurement tool to collect and analyze patient's perceptions of SQ to identify any service pitfall and encourage a faster adoption. To the best of the authors' knowledge, this article is one of the first to investigate and propose a SQ model for DTC telemedicine consultations. This study is therefore motivated by a clear need for such a model as it is currently inexistent. Methods: A literature review of health and e-service quality (e-SQ) models was conducted to identify a suitable instrument for the research. A total of 60 studies were included. Results: The main findings are threefold: (1) DTC telemedicine SQ is interdisciplinary: it encompasses generic and context-specific dimensions from the health, e-SQ, and information system literature; (2) the existing SQ models are not adequate, they do not cover all dimensions of DTC telemedicine services; (3) although LeRouge et al.'s Telemedicine service encounter quality model was identified as a reference model, it is inadequate to simply transpose it to the context of the study. Thus, the elaboration of a more suitable instrument and creation of a new updated model by the authors. Conclusion: The conceptual model captures three primary dimensions (system quality, interaction quality and use quality) that represent SQ of DTC telemedicine consultations from a patient perspective.}, } @article {pmid35771527, year = {2022}, author = {Fragaszy, DM}, title = {Rules and metarules: Adult cotton-top tamarins (Saguinus oedipus) and 5-year-old children (Homo sapiens) can master both.}, journal = {Journal of comparative psychology (Washington, D.C. : 1983)}, volume = {136}, number = {3}, pages = {151-154}, doi = {10.1037/com0000324}, pmid = {35771527}, issn = {1939-2087}, mesh = {Adult ; Animals ; Child, Preschool ; *Cues ; Humans ; *Saguinus/psychology ; }, abstract = {Developmental psychologists have noted a similar timeline of change for children's use of different perspectives about the same objects or events, as in the use of different labels for the same object, an aspect of language, and in understanding other's knowledge or beliefs, an aspect of social cognition as reviewed in the study by Neiworth et al. Comparative psychologists are interested to know what cognitive flexibility looks like in other species and how such variation relates to life history, ecology, and phylogeny. The general pattern of results to date indicates that monkeys can master both intra- and interdimensional shifts, but intradimensional shifts are learned far more quickly than interdimensional shifts (reviewed in the study by Neiworth et al, 2022). Neiworth et al. report that they have conducted exactly this kind of comparative study: They examined cognitive flexibility in adult cotton-top tamarins and human children in three age groups as they participated in a modified version of the Dimensional Change Card Sort (DCCS). Neiworth et al.'s study offers an example of careful consideration of one such possibility: that of using the experimenter's postural orientation to the cards as an inadvertent aid. Here the authors had the benefit of prior work showing that tamarins follow human-provided cues to make a spatially discriminated choice only if the experimenter's head, body, and eyes oriented to a particular location. Thus, in this study, the experimenter kept their head and body centered in the testing space between the two cards and looked at a point on the wall directly behind the midpoint of the testing tray. But the DCCS task, in abstract form, has potentially broader comparative value than to examine cognitive flexibility in primates alone. (PsycInfo Database Record (c) 2022 APA, all rights reserved).}, } @article {pmid35768240, year = {2022}, author = {Takeuchi, K}, title = {Idiopathic plasmacytic lymphadenopathy: A conceptual history along with a translation of the original Japanese article published in 1980.}, journal = {Journal of clinical and experimental hematopathology : JCEH}, volume = {62}, number = {2}, pages = {79-84}, pmid = {35768240}, issn = {1880-9952}, mesh = {*Castleman Disease/diagnosis/pathology ; *Herpesvirus 8, Human ; Humans ; Hypergammaglobulinemia/pathology ; Japan ; *Lymphadenopathy ; }, abstract = {The current consensus on Castleman disease is that it is a group of several distinct lymphoproliferative disorders with different underlying pathogenesis and clinical outcomes. In 1980, Mori et al. proposed the concept of idiopathic plasmacytic lymphadenopathy with polyclonal hyperimmunoglobulinemia (IPL), a disease of unknown etiology, characterized by severe polyclonal hypergammaglobulinemia and generalized superficial lymphadenopathy. After Frizzera et al.'s landmark report in 1983, the term multicentric Castleman disease (MCD) gradually became established, and for a time, IPL was regarded as identical to MCD. However, with the subsequent recognition of human herpesvirus 8 (HHV8)-related MCD in the 1990s and the contributions by Kojima et al. in the 2000s, in which non-HHV8-related MCD (now called idiopathic MCD) was at least subclassified into IPL and others (non-IPL), it is now clear that the original distinctiveness of IPL is still maintained in MCD, which is a diverse collection of diseases.}, } @article {pmid35758557, year = {2022}, author = {Delson, E and Stringer, C}, title = {The naming of Homo bodoensis by Roksandic and colleagues does not resolve issues surrounding Middle Pleistocene human evolution.}, journal = {Evolutionary anthropology}, volume = {31}, number = {5}, pages = {233-236}, doi = {10.1002/evan.21950}, pmid = {35758557}, issn = {1520-6505}, abstract = {Roksandic et al. (2022) proposed the new species name Homo bodoensis as a replacement name for Homo rhodesiensis Woodward, 1921, because they felt it was poorly and variably defined and was linked to sociopolitical baggage. However, the International Code of Zoological Nomenclature includes regulations on how and when such name changes are allowed, and Roksandic et al.'s arguments meet none of these requirements. It is not permitted to change a name solely because of variable (or erroneous) later use once it has been originally defined correctly, nor can a name be modified because it is offensive to one or more authors or to be politically expedient. We discuss past usage of H. rhodesiensis and the relevant nomenclatural procedures, the proposed evolutionary position of H. bodoensis, and issues raised about decolonizing paleoanthropology. We reject H. bodoensis as a junior synonym, with no value from its inception.}, } @article {pmid35752561, year = {2023}, author = {Sarna, K and Ngeow, WC and Kandimalla, A and Akram Estreed, M and Jayant Sonigra, K and Kamau, M}, title = {More than two - A cadaveric study on the morphometry and classification of the digastric muscle in a selected kenyan population.}, journal = {Morphologie : bulletin de l'Association des anatomistes}, volume = {107}, number = {357}, pages = {182-192}, doi = {10.1016/j.morpho.2022.06.001}, pmid = {35752561}, issn = {1286-0115}, mesh = {Humans ; Kenya ; *Neck Muscles ; Hyoid Bone/anatomy & histology ; Cadaver ; *Fractures, Bone ; }, abstract = {BACKGROUND: This study aims to elucidate anatomical variations of the digastric muscle in the Kenyan population.

METHODS: A total of 41 bilateral neck dissections were performed whereby morphologic observations and morphometric measurements were carried out to characterize and classify the various presentations of the muscle.

RESULTS: All cadavers presented with bilateral anterior (ABDM) and posterior (PBDM) bellies of the digastric muscle. Accessory ABDM was observed in 68.3% of cadavers with De-Ary-Pires et al.'s Type II (one accessory belly; 48.8%) and Type III (two accessory bellies; 34.1%) being the most common variations. Unilateral accessory ABDM (43.9%) was more common than bilateral accessory ABDM (24.4%). Two cadavers presented with a mentohyoid muscle. In addition, variations that have not been previously reported, namely fusion of ABDM to the midline and insertion of accessory ABDM into the hyoid bone were observed in one case each. Variation of the PBDM was less prominent, observed at 12.2% of sides dissected. Duplication of PBDM was observed on 4 sides with origin at the mastoid process. The PBDM was longer than the ABDM, but narrower in width. The mean length and width of the ABDM were 4.29±0.72cm and 1.52±1.07cm. The mean length and width of the PBDM were 5.64±1.31cm and 1.07±0.28cm, with the right side being statistically larger than the contralateral side.

CONCLUSION: Variations of the digastric muscle are a common finding, with a high incidence at the ABDM. Two new variants were discovered.}, } @article {pmid35749934, year = {2022}, author = {Hedayati-Azar, A and Sadeghi, H}, title = {Semi-empirical modelling of hydraulic conductivity of clayey soils exposed to deionized and saline environments.}, journal = {Journal of contaminant hydrology}, volume = {249}, number = {}, pages = {104042}, doi = {10.1016/j.jconhyd.2022.104042}, pmid = {35749934}, issn = {1873-6009}, mesh = {Clay ; *Soil ; Solutions ; *Waste Disposal Facilities ; Water ; }, abstract = {Clay liners are widely used as porous membrane barriers to control solute transport and to prevent the leakage of leachate both in horizontal and vertical flow scenarios, such as the isolated base and ramps of sanitary landfills. Despite the primary importance of saturated hydraulic conductivity in a reliable simulation of fluid flow through clay barriers, there is no model to predict hydraulic conductivity of clayey soils permeated with saline aqueous solutions because most of the current models were developed for pure water. Therefore, the main motivation behind this study is to derive semi-empirical models for simulating the hydraulic conductivity of clayey soils in the presence of arbitrary solute concentrations in addition to deionized water. In order to achieve this goal, a relatively comprehensive dataset of 842 measured hydraulic conductivities was retrieved from the experimental literature, where almost 44% of them are related to certain solute concentrations. Afterwards, two modelling approaches were introduced; the first one is a modified form of Mbonimpa et al.'s (2002) model, in which the constants are adjusted to take into consideration the variations in liquid limit due to a change in solute concentration. A modification term was added to the model for the sake of accuracy. In the second approach, a new form of solute concentration-dependent hydraulic conductivity function was proposed, where special attention was given to void ratio and adaptive liquid limit as effective parameters. The results revealed that hydraulic conductivity predictions could be erroneous if the influence of solute concentrations in permeating fluid is ignored. An error analysis was conducted to examine the models' applicability and deviations. A blind independent set of data, including 132 data points, was also used to verify models. On the other hand, both newly proposed models could predict the hydraulic conductivity for a variety of soils, salt species, and concentrations well. Therefore, the proposed modelling approaches are somehow unique by considering the salinity of the pore fluid in addition to deionized water. More importantly, both models are comprised of easy-to-measure parameters with clear physics-based implications.}, } @article {pmid35729792, year = {2022}, author = {Evrard, R and Pratte, E and Rabeyron, T}, title = {Sawing the branch of near-death experience research: A critical analysis of Parnia et al.'s paper.}, journal = {Annals of the New York Academy of Sciences}, volume = {1515}, number = {1}, pages = {5-9}, doi = {10.1111/nyas.14846}, pmid = {35729792}, issn = {1749-6632}, mesh = {Consciousness ; *Death ; Humans ; *Mental Recall ; }, abstract = {In their recent paper, Parnia and colleagues propose a new label for the near-death experience (NDE): recalled experience of death. They claimed NDEs are "authentic" only when an objective danger is present and that authentic NDEs have a proven core phenomenology. We consider that these claims are insufficiently supported by empirical data. NDEs appear as a continuum of heterogeneous experiences of consciousness precipitated by the disjunction of processes usually combined in normal mental activity. The "core phenomenology" of NDEs is also opened to several criticisms. Closeness to "real" death does not appear to be a decisive criterion for characterizing NDEs. The author's adhesion to Raymond Moody's NDE model produces a biased partition of this field of research that is unable to provide the basis for a consensus.}, } @article {pmid35727078, year = {2023}, author = {Norful, AA and Tucker, S and Miller, PS and Roberts, H and Kelley, MM and Monturo, C and O'Mathúna, D and Smith, J and Zadvinskis, IM and Zellefrow, C and Chipps, E}, title = {Nursing perspectives about the critical gaps in public health emergency response during the COVID-19 pandemic.}, journal = {Journal of nursing scholarship : an official publication of Sigma Theta Tau International Honor Society of Nursing}, volume = {55}, number = {1}, pages = {22-28}, pmid = {35727078}, issn = {1547-5069}, mesh = {Humans ; *COVID-19 ; Pandemics ; Public Health ; *Civil Defense ; *Nursing Staff ; Qualitative Research ; }, abstract = {INTRODUCTION: The purpose of this qualitative study was to synthesize frontline U.S. nursing perspectives about the current state of U.S. public health emergency preparedness and response. The study findings may inform public health policy change and improve future national pandemic planning and responses.

DESIGN: We conducted a secondary thematic qualitative analysis using grounded theory methodology.

METHODS: Data collection occurred through semi-structured, in-depth focus groups between July and December 2020, from 43 frontline nurses working in hospitals in four states (Ohio, California, Pennsylvania, and New York). Data were analyzed deductively, aligned with Khan et al.'s Public Health Emergency Preparedness Framework and inductively for emergent themes.

RESULTS: Three themes emerged: (1) Validation of the presence of health disparities and inequities across populations; (2) Perceived lack of consistency and coordination of messaging about pandemic policies and plans across all levels; and (3) challenges securing and allocating nursing workforce resources to areas of need.

CONCLUSION: From a frontline nursing perspective, this study demonstrates the critical need to address health inequities and inequalities across populations, a consistent national vehicle for communication, and national plan for securing and allocating nursing workforce resources.}, } @article {pmid35726854, year = {2022}, author = {Smith, TM and Youngblom, MA and Kernien, JF and Mohamed, MA and Fry, SS and Bohr, LL and Mortimer, TD and O'Neill, MB and Pepperell, CS}, title = {Rapid adaptation of a complex trait during experimental evolution of Mycobacterium tuberculosis.}, journal = {eLife}, volume = {11}, number = {}, pages = {}, pmid = {35726854}, issn = {2050-084X}, support = {R01 AI113287/AI/NIAID NIH HHS/United States ; T32 GM007133/GM/NIGMS NIH HHS/United States ; T32 GM007215/GM/NIGMS NIH HHS/United States ; T32 AI055396/AI/NIAID NIH HHS/United States ; }, mesh = {Biofilms ; Humans ; Multifactorial Inheritance ; *Mycobacterium tuberculosis/genetics ; *Tuberculosis/genetics/microbiology ; }, abstract = {Tuberculosis (TB), caused by Mycobacterium tuberculosis (M. tb), is a leading cause of death due to infectious disease. TB is not traditionally associated with biofilms, but M. tb biofilms are linked with drug and immune tolerance and there is increasing recognition of their contribution to the recalcitrance of TB infections. Here, we used M. tb experimental evolution to investigate this complex phenotype and identify candidate loci controlling biofilm formation. We identified novel candidate loci, adding to our understanding of the genetic architecture underlying M. tb biofilm development. Under selective pressure to grow as a biofilm, regulatory mutations rapidly swept to fixation and were associated with changes in multiple traits, including extracellular matrix production, cell size, and growth rate. Genetic and phenotypic paths to enhanced biofilm growth varied according to the genetic background of the parent strain, suggesting that epistatic interactions are important in M. tb adaptation to changing environments.}, } @article {pmid35726462, year = {2022}, author = {Bastos, JL and Constante, HM and Schuch, HS and Haag, DG and Jamieson, LM}, title = {How do state-level racism, sexism, and income inequality shape edentulism-related racial inequities in contemporary United States? A structural intersectionality approach to population oral health.}, journal = {Journal of public health dentistry}, volume = {82 Suppl 1}, number = {}, pages = {16-27}, doi = {10.1111/jphd.12507}, pmid = {35726462}, issn = {1752-7325}, mesh = {Humans ; Income ; Intersectional Framework ; Oral Health ; *Racism ; Sexism ; United States/epidemiology ; }, abstract = {OBJECTIVE: Research on racial oral health inequities has relied on individual-level data with the premise being that the unequal distribution of dental diseases is an intractable problem. We address these insufficiencies by examining the relationships between structural racism, structural sexism, state-level income inequality, and edentulism-related racial inequities according to a structural intersectionality approach.

METHODS: Data were from two sources, the 2010 survey of the U.S. Behavioral Risk Factor Surveillance System, and Patricia Homan et al.'s (2021) study on the health impacts from interlocking systems of oppression. While the first contains information on edentulism from a large probabilistic sample of older (65+) respondents, the second provides estimates of racism, sexism, and income inequality across the US states. Taking into account a range of individual characteristics and contextual factors in multilevel models, we determine the extent to which structural forms of marginalization underlie racial inequities in edentulism.

RESULTS: Our analysis reveals that structural racism, structural sexism, and state-level income inequality are associated with the overall frequency of edentulism and the magnitude of edentulism-related racial inequities, both individually and intersectionally. Coupled with living in states with both high racism and sexism (but not income inequality), the odds of edentulism were 60% higher among non-Hispanic Blacks, relative to Whites residing where these structural oppressions were at their lowest.

CONCLUSIONS: These findings provide evidence that racial oral health inequities cannot be disentangled from social forces that differentially allocate power and resources among population groups. Mitigating race-based inequities in oral health entails dismantling the multifaceted systems of oppression in the contemporary U.S. society.}, } @article {pmid35726445, year = {2022}, author = {Campbell, KA and Ford-Gilboe, M and Kennedy, K and Jackson, K and Mantler, T and Oudshoorn, A}, title = {Women's experiences of navigating chronic pain within the context of living with an episodic disability.}, journal = {Women's health (London, England)}, volume = {18}, number = {}, pages = {17455057221103994}, pmid = {35726445}, issn = {1745-5065}, mesh = {Canada ; *Chronic Pain/therapy ; *Persons with Disabilities ; Female ; Humans ; Qualitative Research ; Self Care ; }, abstract = {OBJECTIVES: Of the 6.2 million Canadians aged 15 years or older who live with disability, 61% have disabilities that are not static or continuous. These dynamic conditions are known as episodic disabilities and many disproportionately experienced by women. Chronic pain is also a common feature associated with many episodic disabilities. The purpose of this article is to explore the experience of chronic pain for women living with episodic disabilities.

METHODS: This qualitative study draws on the tenets of interpretive description. Thirty women, with one or more episodic disabilities and chronic pain, participated in a semi-structured interview and answered questions about their chronic pain levels, using Von Korff et al.'s graded chronic pain scale.

RESULTS: Women experienced gendered treatment within the healthcare system and reported that they were frequently dismissed by their healthcare providers, most often physicians. Healthcare professionals' practices around pain assessment were another common challenge for women. Women who were able to access financial support from government disability programs were more likely to access allied health professionals. Many of the holistic strategies that women researched and used to treat chronic pain were self-enacted. While diet, exercise, and other self-care activities are general health promotion strategies for all, they were seen as essential aspects of living that helped women have control over chronic pain and modifying the course of their episodic disability.

CONCLUSION: Living with chronic pain and an episodic disability is complex. The findings of this study present the impact that gendered treatment in the healthcare system has on women who live with an episodic disability and experience chronic pain. It is evident that the current system did not meet the needs of the women in our study and system changes could result in better experiences, more disclosure of alternative therapies, and increase women's agency in their care.}, } @article {pmid35725866, year = {2022}, author = {Sacristán, JA and Artime, E and Díaz-Cerezo, S and Comellas, M and Pérez-Carbonell, L and Lizán, L}, title = {The Impact of Patient Support Programs in Europe: A Systematic Literature Review.}, journal = {The patient}, volume = {15}, number = {6}, pages = {641-654}, pmid = {35725866}, issn = {1178-1661}, mesh = {Humans ; *Quality of Life ; *Checklist ; Treatment Outcome ; Europe ; }, abstract = {BACKGROUND AND OBJECTIVE: Patient support programs aim to provide solutions beyond the medication itself, by enhancing treatment adherence, improving clinical outcomes, elevating patient experience, and/or increasing quality of life. As patient support programs increasingly play an important role in assisting patients, numerous observational studies and pragmatic trials designed to evaluate their impact on healthcare have been conducted in recent years. This review aims to characterize these studies.

METHODS: A systematic literature review, supplemented by a broad search of gray literature, was conducted following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and Cochrane recommendations. Observational studies and pragmatic trials conducted in Europe to evaluate the impact of patient support programs, published in English or Spanish between 17/03/2010 and 17/03/2020, were reviewed. Two patient support program definitions were applied starting with Ganguli et al.'s broad approach, followed by the European Medicines Agency definition, narrowed to Marketing Authorization Holders organized systems and their medicines. The quality of publications was assessed using the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) statement 22-item checklist.

RESULTS: Of the 49 identified studies following the Ganguli et al. definition, 20 studies met the European Medicines Agency definition and were reviewed. Patient support program impact was evaluated based on a wide range of methodologies: 70% assessed patient support program-related patient-reported outcomes, 55% reported clinical outcomes, and 25% reported economic impacts on health resources. Only 45% conducted a comparative analysis. Overall, 75% of the studies achieved their proposed objectives.

CONCLUSIONS: The heterogeneity of the observational studies reviewed reflects the complexity of patient support programs that are built ad hoc for specific diseases, treatments, and patients. Results suggest that patient support programs play a key role in promoting treatment effectiveness, clinical outcomes, and satisfaction. However, there is a need for standardizing the definition of patient support programs and the methods to evaluate their impact.}, } @article {pmid35725640, year = {2022}, author = {Oravec, N and Monnin, C and Gregora, A and Bjorklund, B and Dave, MG and Schultz, ASH and Chudyk, AM}, title = {Protocol for a scoping review to map patient engagement in scoping reviews.}, journal = {Research involvement and engagement}, volume = {8}, number = {1}, pages = {27}, pmid = {35725640}, issn = {2056-7529}, abstract = {BACKGROUND: Scoping reviews of health research are increasing in popularity. However, only a minority of scoping reviews in this sector engage patients and caregivers as co-producers of the research. Despite developments in scoping review methodology, which insist that stakeholder consultation is essential, no guiding methods exist to instruct the conduct of this stage. Thus, it is necessary to understand how patients and caregivers have been engaged as part of scoping reviews, toward a unifying methodology.

METHODS: We have developed a protocol for a scoping review of methods used to engage patients and caregivers in scoping reviews of health research. The search strategy will comprise two phases: the first will involve a secondary analysis of retrieved articles from a prior scoping review, and the second will identify articles that cite Levac et al.'s update to the original scoping review framework by Arksey and O'Malley. Titles and full texts of retrieved articles will be screened in duplicate. Inclusion will be limited to articles related to heath research that follow the six-stage scoping review framework by Arksey and O'Malley and that report patient engagement activities during at least one stage. The method of analysis of charted variables will be decided once data have been collected. Two patients will be engaged as collaborators throughout this review. We will also consult with patients, caregivers, and researchers upon completion of preliminary analyses.

DISCUSSION: We anticipate that our scoping review will provide guidance for researchers seeking to involve health care stakeholders as co-producers of scoping reviews.}, } @article {pmid35723577, year = {2022}, author = {Sakaluk, JK and Daniel, A}, title = {How EIRD Is Sex Research?: A Commentary and Reanalysis of Klein et al. (2021).}, journal = {Journal of sex research}, volume = {59}, number = {7}, pages = {818-825}, doi = {10.1080/00224499.2022.2087854}, pmid = {35723577}, issn = {1559-8519}, abstract = {Klein, Savaș, and Conley (2021) argued that sexual science is overdependent on WEIRD (Western, Educated, Industrialized, Rich, and Democratic) samples. Though we agree that sexual science needs to increase its generalizability and inclusivity, we describe concerns with their measurement strategy of categorizing samples as WEIRD or Not WEIRD based on the country from which a sample was drawn. Reanalyzing their data with publicly available global metrics of Education, Industrialization, Richness, and Democratic Values (what we refer to as EIRDness), we find (1) EIRDness metrics were not particularly correlated; (2) countries coded as WEIRD by Klein et al. do not appear reliably EIRDer than those that were not; and (3) and categorical measurement models of EIRDness did not support profiles of EIRD and Not EIRD countries. With these limitations in mind, we then express further concerns about the application utility of Klein et al.'s WEIRDness critique, and unintended political implications embedded in its methodology. We conclude by harkening back to critiques of the WEIRD framework, and suggest that the pursuit of a more equitable and just sexual science - which we applaud Klein et al. for pushing our field to consider - may be better served to alternative frameworks for critiquing its sampling practices.}, } @article {pmid35721087, year = {2022}, author = {Hässler, S and Camilleri-Broët, S and Allez, M and Deisenhammer, F and Fogdell-Hahn, A and Mariette, X and Pallardy, M and Broët, P}, title = {A Genetic Association Test Accounting for Skewed X-Inactivation With Application to Biotherapy Immunogenicity in Patients With Autoimmune Diseases.}, journal = {Frontiers in medicine}, volume = {9}, number = {}, pages = {856917}, pmid = {35721087}, issn = {2296-858X}, abstract = {Despite being assayed on commercialized DNA chips, the X chromosome is commonly excluded from genome-wide association studies (GWAS). One of the reasons is the complexity to analyze the data taking into account the X-chromosome inactivation (XCI) process in women and in particular the XCI process with a potentially skewed pattern. This is the case when investigating the role of X-linked genetic variants in the occurrence of anti-drug antibodies (ADAs) in patients with autoimmune diseases treated by biotherapies. In this context, we propose a novel test statistic for selecting loci of interest harbored by the X chromosome that are associated with time-to-event data taking into account skewed X-inactivation (XCI-S). The proposed statistic relies on a semi-parametric additive hazard model and is straightforward to implement. Results from the simulation study show that the test provides higher power gains than the score tests from the Cox model (under XCI process or its escape) and the Xu et al.'s XCI-S likelihood ratio test. We applied the test to the data from the real-world observational multicohort study set-up by the IMI-funded ABIRISK consortium for identifying X chromosome susceptibility loci for drug immunogenicity in patients with autoimmune diseases treated by biotherapies. The test allowed us to select two single nucleotide polymorphisms (SNPs) with high linkage disequilibrium (rs5991366 and rs5991394) located in the cytoband Xp22.2 that would have been overlooked by the Cox score tests and the Xu et al.'s XCI-S likelihood ratio test. Both SNPs showed a similar protective effect for drug immunogenicity without any occurrence of ADA positivity for the homozygous females and hemizygous males for the alternative allele. To our knowledge, this is the first study to investigate the association between X chromosome loci and the occurrence of anti-drug antibodies. We think that more X-Chromosome GWAS should be performed and that the test is well-suited for identifying X-Chromosome SNPs, while taking into account all patterns of the skewed X-Chromosome inactivation process.}, } @article {pmid35719635, year = {2022}, author = {Wang, J and Tan, Z and Li, J and Wu, Q}, title = {Impact of the Gap Between Social Workers' Work Interaction Frequency With Governments and Clients on Their Burnout in China: Mediating Effects of Role Conflict and Moderating Effects of Non-front-line Work.}, journal = {Frontiers in public health}, volume = {10}, number = {}, pages = {908800}, pmid = {35719635}, issn = {2296-2565}, mesh = {*Burnout, Professional/psychology ; Burnout, Psychological ; China ; Cross-Sectional Studies ; Government ; Humans ; *Social Workers ; Surveys and Questionnaires ; }, abstract = {BACKGROUND: Since the 2000s, local governments have contracted out more and more social services to social work organizations in China. Social workers are thus experiencing the inconsistency between local governments' and clients' demands and the deviation from the professional duty of helping clients, which may result in conflicting and unclear roles in their jobs and further lead to burnout. Based on the Role Stress-burnout Model and the previous theoretical and field-work investigations, this study examined the effects of the government-client work interaction frequency gap on social workers' burnout as well as the mediating effects of role ambiguity and conflict and the moderating effects of the non-front-line work.

METHODS: A cross-sectional study of 2,643 front-line social workers and 2,599 supervisors or managers from 56 major cities all over China was conducted. Work burnout was measured by the 22-item three-dimension Maslach's Burnout Inventory Scale. Rizzo et al.'s 14-item scale measured role conflict and ambiguity. The government-client working interaction frequency gap was measured by the difference between the five-point level of work interaction frequency with governments minus the one with clients. Structural equation modeling was adopted to test the mediation and moderation models.

RESULTS: Results showed that for the front-line social workers, besides directly reducing personal accomplishment, the government-client work interaction frequency gap could indirectly neutralize its alleviating effects on emotional exhaustion (Mediating effect ratio = -63.64 %), make its total effects on depersonalization significant (37.03%), and reduce personal accomplishment further (23.08%) through increasing social workers' feeling of role conflict. However, the above mediating effects of role conflict were not significant for social workers with extra management or supervision workload, revealing the moderating effects of non-front-line work.

CONCLUSIONS: This study revealed that front-line social workers in China who had more work interaction with governments and less with clients could have higher role conflict, increasing their burnout further. Therefore, social work educational programs should include adequate mental adjustment courses and practical emplacement to prepare students for the potential role conflict. Furthermore, higher-level governments should issue relevant regulations to form a collaborative rather than an employment relationship between local governments and social worker organizations.}, } @article {pmid35713755, year = {2022}, author = {Blanchard, R and Skorska, MN}, title = {New Data on Birth Order in Homosexual Men and Women and a Reply to Vilsmeier et al. (2021a, 2021b).}, journal = {Archives of sexual behavior}, volume = {51}, number = {7}, pages = {3319-3349}, pmid = {35713755}, issn = {1573-2800}, mesh = {Birth Order ; Female ; *Homosexuality, Female ; Homosexuality, Male ; Humans ; Male ; Mothers ; *Sexual and Gender Minorities ; Siblings ; }, abstract = {The fraternal birth order effect (FBOE) is the repeated finding that older brothers increase the odds of homosexuality in later-born males. It has been our working assumption, based on the majority of previous studies, that a similar FBOE does not occur in females. In an elaborate quantitative review posted last year to a preprint server, Vilsmeier et al. (2021a) concluded that there is no valid evidence for an FBOE in men or women. Ablaza et al. (2022) subsequently published a study of population-level data from the Netherlands with conclusions completely opposite to those of Vilsmeier et al., namely, that there is robust evidence of an FBOE in both men and women. The present research was initially undertaken to refute the assertion of Vilsmeier et al. that there is no proof of an FBOE in men and to investigate how they obtained such a discrepant conclusion. We found evidence that the discrepancy may relate to Vilsmeier et al.'s use of the large and demonstrably unreliable sample published by Frisch and Hviid (2006). After the publication by Ablaza et al., we expanded our article to address their finding of an FBOE in women. We argue that our preferred explanation of the FBOE in men-that it reflects the progressive immunization of some mothers to Y-linked antigen by each succeeding male fetus and the concomitantly increasing effects of anti-male antibody on sexual differentiation in the brain in each succeeding male fetus-could plausibly be extended to female homosexuality.}, } @article {pmid35708936, year = {2022}, author = {Garinther, A and Arrow, H}, title = {Linguistic framing effects in business and refugee aid contexts: A replication and extension of Cooley et al. (2017).}, journal = {Journal of experimental psychology. General}, volume = {151}, number = {5}, pages = {e1-e18}, doi = {10.1037/xge0000627}, pmid = {35708936}, issn = {1939-2222}, mesh = {Emotions ; Humans ; Linguistics ; Persuasive Communication ; *Refugees ; }, abstract = {Cooley et al. (2017) found that subtle shifts in linguistic framing can enhance the amount of "mind" perceived in a target, and in turn increase feelings of sympathy toward that target. The four studies reported here evaluated whether these findings generalize to different populations and contexts. The first two studies served as conceptual replications in a different participant population (university students, instead of mTurk workers), and found results largely consistent with Cooley et al.'s (2017): the group composition frame ("15 individuals who work for a small accounting company") evoked greater perceptions of experience and agency, and more sympathy for the target, than the group frame ("a small accounting company comprising 15 people"). Studies 3 and 4 tested whether the group composition technique would lead to similar persuasive outcomes (increased mind perception, helping, and donations) in a refugee aid context and found only limited evidence that it might. These inconclusive findings were likely complicated by both the liberal skew of the sample and the strong impact of political identity on responses to the politically charged topic of refugees. For the purposes of practical application, an expanded understanding of boundary effects can help provide a better sense of when, why, and on whom the use of adjusted linguistic frames is most likely to be effective. (PsycInfo Database Record (c) 2022 APA, all rights reserved).}, } @article {pmid35697885, year = {2022}, author = {Smith, JG and Sage, AJ and McGlenn, M and Robbins, J and Garmon, SL}, title = {Is Sexual Racism Still Really Racism? Revisiting Callander et al. (2015) in the USA.}, journal = {Archives of sexual behavior}, volume = {51}, number = {6}, pages = {3049-3062}, pmid = {35697885}, issn = {1573-2800}, mesh = {Bisexuality ; Humans ; Male ; *Racism ; Sexual Behavior ; Sexual Partners ; *Sexual and Gender Minorities ; }, abstract = {As research on race and racism in the USA has suggested that it now takes a more subtle and neoliberal form, one of the areas in which race and racism are most explicit is in dating and sex. When finding dating and sexual partners, people tend to be explicit about their rejection of potential mates along racial lines while claiming that these preferences have no connection with racism. Callander et al.'s (2015) study was the first to provide the evidence that these expressions of sexual racism, or race-based rejections of partners in sexual contexts, were in fact related to cultural racism perpetuated in society at large. Despite all of this, the study has never been replicated. We aimed to partially replicate the study in the USA, using a sample of 616 gay, bisexual, and heterosexual men. Using the Quick Discrimination Index and online sexual racism surveys referenced in the original paper, we find a correlation of - 0.129, between the two measures. This suggests that respondents who demonstrate more openness and less racist beliefs in general are also less likely to be accepting of forms of online sexual racism, a finding that is consistent with prior research. Still, the correlation between these measures is not nearly as strong as that observed in Australia in the original paper (- 0.56), raising questions that require further exploration.}, } @article {pmid35694772, year = {2022}, author = {Watts, PC and Mappes, T and Tukalenko, E and Mousseau, TA and Boratyński, Z and Møller, AP and Lavrinienko, A}, title = {Interpretation of gut microbiota data in the 'eye of the beholder': A commentary and re-evaluation of data from 'Impacts of radiation exposure on the bacterial and fungal microbiome of small mammals in the Chernobyl Exclusion Zone'.}, journal = {The Journal of animal ecology}, volume = {91}, number = {7}, pages = {1535-1545}, pmid = {35694772}, issn = {1365-2656}, support = {287153//Academy of Finland/ ; 324602//Academy of Finland/ ; 268670//Academy of Finland/ ; 324604//Academy of Finland/ ; //Oskar Öflund Stiftelse/ ; //Samuel Freeman Charitable Trust/ ; //Scholarship Fund of the University of Oulu/ ; //University of Oulu Graduate School doctoral programme/ ; }, mesh = {Animals ; Animals, Wild ; Arvicolinae ; Bacteria ; *Chernobyl Nuclear Accident ; Fungi ; *Gastrointestinal Microbiome ; Mammals ; Mice ; Murinae ; *Mycobiome ; *Radiation Exposure ; Radioisotopes ; }, abstract = {Evidence that exposure to environmental pollutants can alter the gut microbiota composition of wildlife includes studies of rodents exposed to radionuclides. Antwis et al. (2021) used amplicon sequencing to characterise the gut microbiota of four species of rodent (Myodes glareolus, Apodemus agrarius, A. flavicollis and A. sylvaticus) inhabiting the Chernobyl Exclusion Zone (CEZ) to examine possible changes in gut bacteria (microbiota) and gut fungi (mycobiota) associated with exposure to radionuclides and whether the sample type (from caecum or faeces) affected the analysis. The conclusions derived from the analyses of gut mycobiota are based on data that represent a mixture of ingested fungi (e.g. edible macrofungi, polypores, lichens and ectomycorrhizae) and gut mycobiota (e.g. microfungi and yeasts), which mask the patterns of inter- and intraspecific variation in the authentic gut mycobiota. Implying that 'faecal samples are not an accurate indicator of gut composition' creates an unnecessary controversy about faecal sampling because the comparison of samples from the caecum and faeces confounds many other possible drivers (including different animals from different locations, sampled in different years) of variation in gut microbiota. It is relevant also that Antwis et al.'s (2021) data lack statistical power to detect an effect of exposure to radionuclides on the gut microbiota because (1) all of their samples of Apodemus mice had experienced a medium or high total absorbed dose rate and (2) they did not collect samples of bank voles (M. glareolus) from replicate contaminated and uncontaminated locations. Discussion of Antwis et al.'s (2021) analysis, especially the claims presented in the Abstract, is important to prevent controversy about the outcome of research on the biological impacts of wildlife inhabiting the CEZ.}, } @article {pmid35691653, year = {2022}, author = {Abd Naeeim, NS and Abdul Rahman, N}, title = {Spatio-temporal clustering analysis using two different scanning windows: A case study of dengue fever in Peninsular Malaysia.}, journal = {Spatial and spatio-temporal epidemiology}, volume = {41}, number = {}, pages = {100496}, doi = {10.1016/j.sste.2022.100496}, pmid = {35691653}, issn = {1877-5853}, mesh = {Animals ; Cluster Analysis ; *Dengue/epidemiology ; Humans ; Incidence ; Malaysia/epidemiology ; Spatio-Temporal Analysis ; }, abstract = {Dengue fever is a mosquito-borne viral infection of humans caused by a virus of the Flaviviridae family. In Malaysia the annual incidence risk of dengue fever for the period 2000 to 2019 ranged from 30 to 390 cases per 100,000. The aim of this paper was to identify spatial, temporal and spatio-temporal clusters of dengue fever in Peninsular Malaysia for the period 2015 to 2017. Counts of confirmed incident cases of dengue fever for each of the 86 districts of Peninsular Malaysia for the period 1 January 2015 to 31 December 2017 (inclusive) and district-level census data allowed us to calculate the incidence rate of dengue fever, defined as the number of confirmed cases of dengue fever per 100,000 person-years at risk. We applied Kulldorff's cylindrical space-time scan statistic and Takahashi et al.'s prismatic space-time scan statistic to the data. We identified no major differences in the number and location of spatial clusters of dengue incidence for 2015, 2016 and 2017 using Kulldorff's and Takahashi et al.'s method. Spatio-temporal clusters of dengue occurred at several times throughout each year in various high population dense areas. These clusters not only included high population density districts but also their adjacent district neighbours. The temporal clustering of dengue cases during the monsoon season (mid September to late December each year) implies that there is a biologically plausible causal association between rainfall and the incidence of dengue. Identification of locations and time periods when the frequency of dengue is high allows Malaysian public health authorities to be more objective in their decision making around vector control and dengue public awareness campaigns. Future research will quantify the association between population density and rainfall on dengue incidence. This will allow health authorities to take a more proactive approach for dengue control.}, } @article {pmid35672710, year = {2022}, author = {Desta, BN and Gobena, T and Macuamule, C and Fayemi, OE and Ayolabi, CI and Mmbaga, BT and Thomas, KM and Dodd, W and Pires, SM and Majowicz, SE and Hald, T}, title = {Practicalities of implementing burden of disease research in Africa: lessons from a population survey component of our multi-partner FOCAL research project.}, journal = {Emerging themes in epidemiology}, volume = {19}, number = {1}, pages = {4}, pmid = {35672710}, issn = {1742-7622}, support = {INV-008445//Bill & Melinda Gates Foundation (BMGF)/ ; OPP1195617//Foreign, Commonwealth & Development Office (FCDO) of the United Kingdom Government/ ; }, abstract = {BACKGROUND: Collaborative research is being increasingly implemented in Africa to study health-related issues, for example, the lack of evidence on disease burden, in particular for the presumptive high load of foodborne diseases. The FOCAL (Foodborne disease epidemiology, surveillance, and control in African LMIC) Project is a multi-partner study that includes a population survey to estimate the foodborne disease burden in four African low- and middle-income countries (LMICs). Our multi-partner study team had members from seven countries, all of whom contributed to the project from the grant application stage, and who play(ed) specific roles in designing and implementing the population survey.

MAIN TEXT: In this paper, we applied Larkan et al.'s framework for successful research partnerships in global health to self-evaluate our project's collaboration, management, and implementation process. Our partnership formation considered the interplay and balance between operations and relations. Using Larkan et al.'s seven core concepts (i.e., focus, values, equity, benefit, communication, leadership, and resolution), we reviewed the process stated above in an African context.

CONCLUSION: Through our current partnership and research implementing a population survey to study disease burden in four African LMICs, we observed that successful partnerships need to consider these core concepts explicitly, apply the essential leadership attributes, perform assessment of external contexts before designing the research, and expect differences in work culture. While some of these experiences are common to research projects in general, the other best practices and challenges we discussed can help inform future foodborne disease burden work in Africa.}, } @article {pmid35669718, year = {2022}, author = {Shady, K and Phillips, S and Newman, S}, title = {Barriers and Facilitators to Healthcare Access in Adults with Intellectual and Developmental Disorders and Communication Difficulties: an Integrative Review.}, journal = {Review journal of autism and developmental disorders}, volume = {}, number = {}, pages = {1-13}, pmid = {35669718}, issn = {2195-7185}, abstract = {UNLABELLED: This integrative review explores the barriers to and facilitators of healthcare access in adults with intellectual and developmental disorders (IDD) and communication difficulties (CD) using Levesque et al.'s conceptual framework of access to health. IDDs are a group of disorders that occur early in childhood and often involve language dysfunction. CDs are prevalent in adults with IDD. Several themes emerged as barriers to access for adults with IDDs and CDs including health literacy, understanding health information, and screening; fear and negative patient expectations; impaired autonomy; time; accommodation needs; insurance coverage and financial hardship; communication; coordination and continuity of care; and supporter presence and inclusion. Communication between providers, patients, and supporters is a significant barrier for adults with IDD and CD.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40489-022-00324-8.}, } @article {pmid35666917, year = {2022}, author = {Burlingame, GM and Rosendahl, J}, title = {A scientific response to Moritz et al. (2022).}, journal = {Psychotherapy (Chicago, Ill.)}, volume = {59}, number = {2}, pages = {136-139}, doi = {10.1037/pst0000433}, pmid = {35666917}, issn = {1939-1536}, abstract = {This brief response addresses questions and concerns raised by Moritz and colleagues regarding our Burlingame et al.'s (2020) meta-analysis of group protocols effectiveness with patients diagnosed with schizophrenia (PsycInfo Database Record (c) 2022 APA, all rights reserved).}, } @article {pmid35666899, year = {2022}, author = {Nicolotti, LM}, title = {Commentary on Integration of primary care and behavioral health services in Midwestern community health centers: A mixed methods study.}, journal = {Families, systems & health : the journal of collaborative family healthcare}, volume = {40}, number = {2}, pages = {286-287}, doi = {10.1037/fsh0000712}, pmid = {35666899}, issn = {1939-0602}, mesh = {Health Services ; Humans ; Primary Health Care ; *Psychiatry ; *Public Health ; Referral and Consultation ; }, abstract = {Comments on the original article by Staab et al. (see record 2022-14598-001) regarding the integration of primary care and behavioral health services in Midwestern community health centers. As a clinician, the author identifies with many of the findings in Staab et al.'s paper. Limited resources related to patient access were cited as a barrier to integration. In the academic medical center and the larger community, we have experienced too few behavioral health providers (BHPs) to meet the increasing demand for behavioral health (BH) services. There are long waitlists for BH care, and patients report difficulty accessing appropriate BH resources. A lack of funding within the health care system has been a barrier to hiring an adequate BH workforce to meet the demand of internal and external BH referrals. Integrated care requires a specific set of skills and training experiences to competently provide brief interventions and work as part of an interdisciplinary medical team in a fast-paced medical setting. The pool of qualified applicants for integrated care positions is limited, challenging recruitment efforts. Another factor reducing access within the integrated care setting is difficulty adhering to a short-term treatment model with patients who have severe mental health issues and long-term therapy needs, given their difficulty obtaining longer-term services. Unlike the majority of community health centers (CHCs) in this study, we have insufficient social work support to adequately meet all patients' care management needs. (PsycInfo Database Record (c) 2022 APA, all rights reserved).}, } @article {pmid35666898, year = {2022}, author = {Beachy, B and Bauman, D}, title = {Clinician's commentary to accompany "Implementing evidence-based practices in non-specialty mental health settings".}, journal = {Families, systems & health : the journal of collaborative family healthcare}, volume = {40}, number = {2}, pages = {283-285}, doi = {10.1037/fsh0000711}, pmid = {35666898}, issn = {1939-0602}, mesh = {Evidence-Based Practice ; Humans ; *Mental Health ; *Mental Health Services ; }, abstract = {Comments on the original article by Wolk et al. (see record 2022-18591-001) regarding the implementation of evidence-based practices in non-specialty mental health settings. The authors both had tremendous gratitude for Wolk et al.'s (2022) ability to accurately describe and elucidate numerous difficulties that frontline workers experience, especially in nonspecialty mental health (SMH) settings, such as primary care where we work. With increased identification of implementation barriers, those working in non-SMH settings can mitigate these challenges via intentional strategizing upfront, considering settings' contexts (as suggested by Wolk et al.), and normalizing the need for ongoing troubleshooting. The authors appreciated the elucidation that the majority of those receiving support for mental health receive care in non-SMH settings. As much as it is imperative for those working in non-SMH settings to learn concepts illuminated from the mental health field via evidence-based (EB) practices, when it comes to reaching the masses and implementation strategies, the field might have much to learn from these non-SMH settings. When it comes to integration of siloed fields, all can benefit. (PsycInfo Database Record (c) 2022 APA, all rights reserved).}, } @article {pmid35662513, year = {2022}, author = {Charns, MP and Bolton, RE}, title = {Commentary on Burns, Nembhard and Shortell, "Integrating network theory into the study of integrated healthcare": Revisiting and extending research on structural and processual factors affecting coordination.}, journal = {Social science & medicine (1982)}, volume = {305}, number = {}, pages = {115037}, doi = {10.1016/j.socscimed.2022.115037}, pmid = {35662513}, issn = {1873-5347}, mesh = {*Burns ; Communication ; *Delivery of Health Care, Integrated ; Health Facilities ; Humans ; Qualitative Research ; }, abstract = {Burns et al.'s innovative recommendation to use social network theory to study integration will contribute to our understanding of how healthcare systems can optimally deliver high quality, coordinated, person-centered care. We discuss three enhancements to this approach. (1) In increasing our attention to social network analysis and processual perspectives, we must not "throw out the baby with the bathwater" and abandon research that includes formal organizational structure. Structure remains an important focus for researchers and healthcare managers, who spend considerable resources on reorganizing. Since there is evidence that formal structure affects social processes and coordination, future research should build on that evidence and investigate how coordination is affected by the segmentation of organizations into units and the structures and processes designed to integrate interdependent work across those units. Conducting network analysis in the context of formal structure can help us better understand how formal structure affects both social networks and coordination. (2) Using multi-level, mixed methods, and qualitative research will be critically important to fully understand how and why formal organizational structure, social networks, and processual dynamics contribute to coordination or fragmentation of care. Because the relationships among these constructs occur not only within, but also across multiple levels, multi-level research is necessary to understand their effects on coordination. In considering the individual level, patients can be studied as a role embedded in networks. In addition, however, we must not lose a focus on patients as people at the center of multi-level networks, whose attitudes, values, preferences and goals may directly affect processual dynamics and coordination of care. (3) Finally, our field lacks precision in nomenclature, specification of levels, and the constructs within them, including ambiguity around even what is meant by "structure" and its variations. Furthermore, different authors use "macro", "meso", and "micro", differently, contributing to confusion in the discourse on organizational phenomena. Greater clarity and consistency in terminology is needed to facilitate research and improve communication across the field.}, } @article {pmid35659472, year = {2023}, author = {Evans, KM and Buser, TJ and Larouche, O and Kolmann, MA}, title = {Untangling the relationship between developmental and evolutionary integration.}, journal = {Seminars in cell & developmental biology}, volume = {145}, number = {}, pages = {22-27}, doi = {10.1016/j.semcdb.2022.05.026}, pmid = {35659472}, issn = {1096-3634}, mesh = {*Biological Evolution ; Phenotype ; }, abstract = {Patterns of integration and modularity among organismal traits are prevalent across the tree of life, and at multiple scales of biological organization. Over the past several decades, researchers have studied these patterns at the developmental, and evolutionary levels. While their work has identified the potential drivers of these patterns at different scales, there appears to be a lack of consensus on the relationship between developmental and evolutionary integration. Here, we review and summarize key studies and build a framework to describe the conceptual relationship between these patterns across organismal scales and illustrate how, and why some of these studies may have yielded seemingly conflicting outcomes. We find that among studies that analyze patterns of integration and modularity using morphological data, the lack of consensus may stem in part from the difficulty of fully disentangling the developmental and functional causes of integration. Nonetheless, in some empirical systems, patterns of evolutionary modularity have been found to coincide with expectations based on developmental processes, suggesting that in some circumstances, developmental modularity may translate to evolutionary modularity. We also advance an extension to Hallgrímsson et al.'s palimpsest model to describe how patterns of trait modularity may shift across different evolutionary scales. Finally, we also propose some directions for future research which will hopefully be useful for investigators interested in these issues.}, } @article {pmid35657484, year = {2022}, author = {Garashi, HY and Steinke, DT and Schafheutle, EI}, title = {A Systematic Review of Pharmacovigilance Systems in Developing Countries Using the WHO Pharmacovigilance Indicators.}, journal = {Therapeutic innovation & regulatory science}, volume = {56}, number = {5}, pages = {717-743}, pmid = {35657484}, issn = {2168-4804}, mesh = {Data Collection ; *Developing Countries ; *Pharmacovigilance ; World Health Organization ; }, abstract = {BACKGROUND: In the context of the growth of pharmacovigilance (PV) among developing countries, this systematic review aims to synthesise current research evaluating developing countries' PV systems' performance.

METHODS: EMBASE, MEDLINE, CINAHL Plus and Web of Science were searched for peer-reviewed studies published in English between 2012 and 2021. Reference lists of included studies were screened. Included studies were quality assessed using Hawker et al.'s nine-item checklist; data were extracted using the WHO PV indicators checklist. Scores were assigned to each group of indicators and used to compare countries' PV performance.

RESULTS: Twenty-one unique studies from 51 countries were included. Of a total possible quality score of 36, most studies were rated medium (n = 7 studies) or high (n = 14 studies). Studies obtained an average score of 17.2 out of a possible 63 of the WHO PV indicators. PV system performance in all 51 countries was low (14.86/63; range: 0-26). Higher average scores were obtained in the 'Core' (9.27/27) compared to 'Complementary' (5.59/36) indicators. Overall performance for 'Process' and 'Outcome' indicators was lower than that of 'Structural'.

CONCLUSION: This first systematic review of studies evaluating PV performance in developing countries provides an in-depth understanding of factors affecting PV system performance.}, } @article {pmid35642738, year = {2023}, author = {Drescher, J}, title = {Informed Consent or Scare Tactics? A Response to Levine et al.'s "Reconsidering Informed Consent for Trans-Identified Children, Adolescents, and Young Adults".}, journal = {Journal of sex & marital therapy}, volume = {49}, number = {1}, pages = {99-107}, doi = {10.1080/0092623X.2022.2080780}, pmid = {35642738}, issn = {1521-0715}, mesh = {Humans ; Child ; Adolescent ; Young Adult ; *Transsexualism/therapy ; Informed Consent ; *Transgender Persons ; Gender Identity ; Fear ; Male ; Female ; }, abstract = {This responds to "Reconsidering Informed Consent for Trans-Identified Children, Adolescents, and Young Adults" by Levine et al., part of a small but growing, critical response to contemporary treatments of gender dysphoric/incongruent (GD/GI) children and adolescents. This author, while disagreeing with Levine et al. and other critics, hopes that with dialogue, research and engagement with the wider world, needs of all children, adolescents and young adults-those who have GD/GI and those who may not-will be best served. Critics of gender affirming treatments cite growing numbers of cases, "low level of evidence" supporting treatment, irreversible side effects and expressing regrets as reasons to oppose gender affirmative treatments. Although sharing similar concerns, the author does not conclude treatments should not be offered when appropriate. The critics' alternative reads as "just talk to the young people and find out what is really bothering them." Lacking empirical evidence for that approach does not appear to trouble them.Levine et al.'s caricature of informed consent, which this author parodies, would dissuade anyone from treatment. Their approach does not appear to be written for purposes of engaging frontline clinicians with the aim of improving treatment. Instead, they read as appeals to third parties unfamiliar with the clinical presentations of these children-parents, caretakers courts, legislatures, state health departments and national health care systems-to discourage treatments from proceeding. This impression is further buttressed by a declaration of financial support from The Society for Empirical-Based Gender Medicine, a small group of outliers from mainstream clinicians treating minors with GD/GI who present as "truth-speaking" experts regarding "facts" being ignored, elided over or perhaps even covered up by the mainstream.The author concludes by noting that clinicians who advocate for delaying treatment to GD/GI minors who need and may benefit from it to "protect" those who "aren't really" transgender is an ethically troubling issue. In other words, "first, do no harm" is a sword that cuts two ways.}, } @article {pmid35642413, year = {2022}, author = {Iqbal, W and Andalib, S and Hasan Mohani, SNU and Hasan, MM and Arman, M and Ali, L}, title = {Elemental analysis of carrageenans isolated from Hypnea musciformis red algae of Karachi coast using SEM-EDX.}, journal = {Pakistan journal of pharmaceutical sciences}, volume = {35}, number = {2}, pages = {561-570}, pmid = {35642413}, issn = {1011-601X}, mesh = {*Biological Products ; Carrageenan ; Minerals ; Polysaccharides ; *Rhodophyta ; Sodium ; }, abstract = {The carrageenans with high molecular weight, crude and dialysed polysaccharide fractions obtained from Hypnea musciformis red algae of Karachi coast in Pakistan. The elemental composition was determined by using SEM-EDX technique which is one of the modern, reliable and accurate techniques. After analyzing multiple mineral elements were detected in different quantities. The numbers of elements found in crude extracts were greater than that in the dialysed extracts. All extracts contained the higher concentrations of C followed by O (except dialysed acidic extract). Among other elements, Cl and K were present in the highest amounts (>25.0%) in dialysed acidic extracts. However, Al was detected in low concentrations in only crude aqueous and acidic extracts. The mineral concentrations ranges were 30.34-52.46%, 17.00-43.46%, 0.63-4.05%, 0.49-3.35%, 0-0.33%, 0.74-17.92%, 0.59-25.31%, 0.58-25.46%, 1.10-6.72%, 0-2.60% for C, O, Na, Mg, Al, S, Cl, K, Ca and Zn in these crude and dialyzed extracts respectively. The study confirmed the presence of major elements such that Na, Mg, Ca, K and Zn in high quantities. However, there was no toxic element identified like Cd, Hg and Pb which show that these carrageenans are safer to utilize in food and pharmaceutical industries.}, } @article {pmid35639087, year = {2022}, author = {Manstead, ASR}, title = {Commentary on "how emotions, relationships, and culture constitute each other: advances in social functionalist theory" by Keltner, Sauter, Tracy, Wetchler, and Cowen.}, journal = {Cognition & emotion}, volume = {36}, number = {3}, pages = {402-405}, doi = {10.1080/02699931.2022.2035687}, pmid = {35639087}, issn = {1464-0600}, mesh = {*Emotions ; Humans ; }, abstract = {This paper is a commentary on the paper by Keltner and colleagues (this issue). Although Keltner at al.'s expanded version of a social functionalist theory of emotion is a welcome addition to theoretical thinking about the relation between emotion and social life, I argue that their paper accords too much importance to the ways in which emotion is shaped by the relational needs of the individual, and too little to the cultural context in which relationships take place.}, } @article {pmid35635085, year = {2023}, author = {Baldt, B and Slunecko, T}, title = {Shared Medical Decision Making Reconsidered: Challenging an Overly Cognitivist Perspective with a Linguistic Approach.}, journal = {Health communication}, volume = {38}, number = {11}, pages = {2281-2291}, doi = {10.1080/10410236.2022.2065736}, pmid = {35635085}, issn = {1532-7027}, support = {P 29509/FWF_/Austrian Science Fund FWF/Austria ; }, mesh = {Humans ; *Decision Making, Shared ; *Decision Making ; Physician-Patient Relations ; Clinical Decision-Making/methods ; Linguistics ; Patient Participation/methods ; }, abstract = {This article critically examines the four patterns of shared medical decision making (physician-dominated; physician-defined, patient-made; patient-defined, physician-made; and patient-dominated) suggested by Lippa et al. (2017). The aim of the study is to challenge these patterns with a new data set of conversations between physicians and cancer patients in a hospital ward. We recorded 13 physician-patient-conversations during the medical round in an Austrian hospital, which in total lasted about 1.5 h (language: German). We then categorized the medical decisions found in the data following Lippa et al.'s instructions and further analyzed them with a fine-grained linguistic approach. The study revealed no patient-dominated decisions and one decision, which could not be categorized with one of the patterns. Results from the linguistic approach call into question the generalizability, distinctiveness and validity of the patterns. Finally, the relationship between shared decision making and clinical distributed cognition is discussed.}, } @article {pmid35632834, year = {2022}, author = {Sul, H and Yun, NR and Kim, DM and Kim, YK and Kim, J and Hur, J and Jung, SI and Ryu, SY and Lee, JY and Huh, K and Kwak, YG and Jeong, HW and Heo, JY and Jung, DS and Lee, SH and Park, SH and Yeom, JS and Lee, H}, title = {Development of a Scoring System to Differentiate Severe Fever with Thrombocytopenia Syndrome from Scrub Typhus.}, journal = {Viruses}, volume = {14}, number = {5}, pages = {}, pmid = {35632834}, issn = {1999-4915}, mesh = {Humans ; *Leukopenia/diagnosis ; *Phlebovirus ; Retrospective Studies ; *Scrub Typhus/diagnosis/epidemiology ; *Severe Fever with Thrombocytopenia Syndrome/diagnosis ; *Thrombocytopenia/diagnosis ; }, abstract = {Severe fever with thrombocytopenia syndrome (SFTS) and scrub typhus are disorders with similar clinical features; therefore, differentiating between them is difficult. We retrospectively collected data from 183 SFTS and 178 scrub typhus patients and validated an existing scoring system to develop a more sensitive, specific, and objective scoring system. We first applied the scoring systems proposed by Kim et al. to differentiate SFTS from scrub typhus. Multivariable logistic regression revealed that altered mental status, leukopenia, prolonged activated partial thromboplastin time (aPTT), and normal C-reactive protein (CRP) level (≤1.0 mg/dL) were significantly associated with SFTS. We changed the normal CRP level from ≤1.0 mg/dL to ≤3.0 mg/dL and replaced altered mental status with the creatine kinase (CK) level. The modified scoring system showed 97% sensitivity and 96% specificity for SFTS (area under the curve (AUC): 0.983) and a higher accuracy than the original scoring system (p = 0.0308). This study’s scoring system had 97% sensitivity and 98% specificity for SFTS (AUC: 0.992) and a higher accuracy than Kim et al.’s original scoring system (p = 0.0308). Our scoring system that incorporated leukopenia, prolonged aPTT, normal CRP level (≤3.0 mg/dL), and elevated CK level (>1000 IU/L) easily differentiated SFTS from scrub typhus in an endemic area.}, } @article {pmid35602625, year = {2022}, author = {Ye, Q and Wang, M and Meng, H and Xia, F and Yan, X}, title = {Efficient Linkable Ring Signature Scheme over NTRU Lattice with Unconditional Anonymity.}, journal = {Computational intelligence and neuroscience}, volume = {2022}, number = {}, pages = {8431874}, pmid = {35602625}, issn = {1687-5273}, mesh = {*Algorithms ; *Computer Security ; }, abstract = {In cloud and edge computing, senders of data often want to be anonymous, while recipients of data always expect that the data come from a reliable sender and they are not redundant. Linkable ring signature (LRS) can not only protect the anonymity of the signer, but also detect whether two different signatures are signed by the same signer. Today, most lattice-based LRS schemes only satisfy computational anonymity. To the best of our knowledge, only the lattice-based LRS scheme proposed by Torres et al. can achieve unconditional anonymity. But the efficiency of signature generation and verification of the scheme is very low, and the signature length is also relatively long. With the preimage sampling, trapdoor generation, and rejection sampling algorithms, this study proposed an efficient LRS scheme with unconditional anonymity based on the e-NTRU problem under the random oracle model. We implemented our scheme and Torres et al.'s scheme, as well as other four efficient lattice-based LRS schemes. It is shown that under the same security level, compared with Torres et al.'s scheme, the signature generation time, signature verification time, and signature size of our scheme are reduced by about 94.52%, 97.18%, and 58.03%, respectively.}, } @article {pmid35601563, year = {2022}, author = {Kamogne Tagne, CT and Brittain, S and Booker, F and Challender, D and Maddison, N and Milner-Gulland, EJ and Mouamfon, M and Roe, D and Coad, L}, title = {Impacts of the COVID-19 pandemic on livelihoods and wild meat use in communities surrounding the Dja Faunal Reserve, South-East Cameroon.}, journal = {African journal of ecology}, volume = {60}, number = {2}, pages = {135-145}, pmid = {35601563}, issn = {0141-6707}, abstract = {The COVID-19 outbreak has had considerable negative impacts on the livelihoods and living conditions of communities around the world. Although the source of COVID-19 is still unknown, a widely spread hypothesis is that the virus could be of animal origin. Wild meat is used by rural communities as a source of income and food, and it has been hypothesised that the pandemic might alter their perceptions and use of wild meat. McNamara et al. (2020) developed a causal model hypothesising how the impacts of the pandemic could lead to a change in local incentives for wild meat hunting in sub-Saharan African countries. From February 27 to March 19, 2021, we carried out a survey around the Dja Faunal Reserve, Southeast Cameroon, to test McNamara et al.'s model in practice, using semi-structured questionnaires to investigate the impacts of the COVID-19 outbreak on wild meat hunting and consumption. Our results generally agree with the causal pathways suggested by McNamara et al. However, our study highlights additional impact pathways not identified in the model. We provide revisions to McNamara's model to incorporate these pathways and inform strategies to mitigate the impacts of the pandemic.}, } @article {pmid35594382, year = {2023}, author = {Kelley, LJ and Saenz, I and Curtis, DA}, title = {An analysis of Lilienfeld et al.'s (2015) problematic psychological terms.}, journal = {The Journal of general psychology}, volume = {150}, number = {3}, pages = {344-362}, doi = {10.1080/00221309.2022.2076060}, pmid = {35594382}, issn = {1940-0888}, mesh = {Humans ; *Health Personnel ; *Language ; }, abstract = {The language psychologists and other mental health professionals utilize impacts the formation of public perceptions concerning the practice of psychology. Psychologists from Warren, Calkins, Dunlap, Gardiner, and Ruckmich to Lilienfeld et al. have raised concerns about the clarity and use of problematic psychological terms. This study measured 309 mental health professionals' (1) recognition and use of 50 psychological terms identified as problematic by Lilienfeld et al., and (2) explored the jangle fallacy by providing potentially synonymous word-pairs for participants to rate for synonymity. Results of Part I indicated that 34 out of the 50 terms were not recognized as problematic by a significant majority of participants. Participants disagreed about whether or not six terms were problematic, and the remaining 10 terms were rated by a majority to be problematic. Results of Part II indicated a disagreement between participants regarding the synonymity of four word-pairs, and agreement regarding the synonymity (or lack thereof) of the remaining 16 word-pairs. These findings support the suggestion by Lilienfeld and colleagues that greater attention is needed in regard to problematic psychological terminology, including synonymous or jangling terminology.}, } @article {pmid35585426, year = {2022}, author = {Medeiros, APM and Santos, BA and Betancur-R, R}, title = {Does genome size increase with water depth in marine fishes?.}, journal = {Evolution; international journal of organic evolution}, volume = {76}, number = {7}, pages = {1578-1589}, doi = {10.1111/evo.14510}, pmid = {35585426}, issn = {1558-5646}, mesh = {Animals ; *Fishes/genetics ; Genome Size ; Phylogeny ; *Water ; }, abstract = {A growing body of research suggests that genome size in animals can be affected by ecological factors. Half a century ago, Ebeling et al. proposed that genome size increases with depth in some teleost fish groups and discussed a number of biological mechanisms that may explain this pattern (e.g., passive accumulation, adaptive acclimation). Using phylogenetic comparative approaches, we revisit this hypothesis based on genome size and ecological data from up to 708 marine fish species in combination with a set of large-scale phylogenies, including a newly inferred tree. We also conduct modeling approaches of trait evolution and implement a variety of regression analyses to assess the relationship between genome size and depth. Our reanalysis of Ebeling et al.'s dataset shows a weak association between these variables, but the overall pattern in their data is driven by a single clade. Although new analyses based on our "all-species" dataset resulted in positive correlations, providing some evidence that genome size evolves as a function of depth, only one subclade consistently yielded statistically significant correlations. By contrast, negative correlations are rare and nonsignificant. All in all, we find modest evidence for an increase in genome size along the depth axis in marine fishes. We discuss some mechanistic explanations for the observed trends.}, } @article {pmid35584100, year = {2022}, author = {Rich, C and Mavhu, W and France, NF and Munatsi, V and Byrne, E and Willis, N and Nolan, A}, title = {Exploring the beliefs, experiences and impacts of HIV-related self-stigma amongst adolescents and young adults living with HIV in Harare, Zimbabwe: A qualitative study.}, journal = {PloS one}, volume = {17}, number = {5}, pages = {e0268498}, pmid = {35584100}, issn = {1932-6203}, mesh = {Adolescent ; Adult ; *COVID-19 ; Female ; *HIV Infections/epidemiology ; Humans ; Male ; Qualitative Research ; Quality of Life ; SARS-CoV-2 ; Social Stigma ; Young Adult ; Zimbabwe ; }, abstract = {BACKGROUND: HIV-related self-stigma is a significant barrier to HIV management. However, very little research has explored this phenomenon, particularly in sub-Saharan Africa. This study explored the beliefs, experiences, and impacts of HIV self-stigma amongst adolescents and young adults (AYALHIV) in Harare, Zimbabwe to inform future interventions. It aimed to capture the lived experience of self-stigmatization among AYALHIV and its impact on their social context using Corrigan et al (2009) self-stigma framework of 'awareness', 'agreement', and 'application'.

METHODS: Virtual semi-structured key informant interviews were conducted between June and July 2020 with adolescents and young adults (Female = 8; Male = 8) living with HIV (18-24 years) in Harare, Zimbabwe. We conducted the interviews with a purposive sample of AYALHIV enrolled in Africaid's 'Zvandiri' program which provides HIV support services. Interviews were mainly conducted in English and with three in Shona, the main indigenous language. Audio-recorded qualitative data were transcribed, translated into English (where necessary) and deductively coded using Corrigan et al.'s self-stigma framework. The outbreak of SARS-CoV-2 coincided with the commencement of data collection activities, which impacted on both the sample size and a shift from in-person to virtual interviewing methods.

RESULTS: Sixteen respondents (50% male) took part in the interviews. The mean age of respondents was 22 years. All respondents reported HIV-related self-stigma either occasionally or frequently. Three main themes of self-stigmatizing experiences emerged: disclosure, relationships, and isolation. These themes were then analyzed within the self-stigma development framework by Corrigan et al. (2009) known as 'the three As': awareness, agreement, and application of self-stigmatizing thoughts. Respondents' experiences of self-stigma reportedly led to poor well-being and decreased mental and physical health. Gendered experiences and coping mechanisms of self-stigma were reported. Data suggested that context is key in the way that HIV is understood and how it then impacts the way people living with HIV (PLHIV) live with, and experience, HIV.

CONCLUSIONS: HIV-related negative self-perceptions were described by all respondents in this study, associated with self-stigmatizing beliefs that adversely affected respondents' quality of life. Study findings supported Corrigan et al.'s framework on how to identify self-stigma and was a useful lens through which to understand HIV-related self-stigma among young people in Harare. Study findings highlight the need for interventions targeting PLHIV and AYALHIV to be context relevant if they are to build individual resilience, while working concurrently with socio-political and systemic approaches that challenge attitudes to HIV at the wider societal levels. Finally, the gendered experiences of self-stigma point to the intersecting layers of self-stigma that are likely to be felt by particularly marginalized populations living with HIV and should be further explored.}, } @article {pmid35583077, year = {2022}, author = {Sergi, CM}, title = {Commentary on: SMARCB1 as a novel diagnostic and prognostic biomarker for osteosarcoma.}, journal = {Bioscience reports}, volume = {42}, number = {6}, pages = {}, pmid = {35583077}, issn = {1573-4935}, mesh = {Biomarkers, Tumor/genetics/metabolism ; *Bone Neoplasms/diagnosis/genetics ; Humans ; *Osteosarcoma/diagnosis/genetics ; Prognosis ; *Rhabdoid Tumor/diagnosis/genetics/pathology ; SMARCB1 Protein/genetics ; Sucrose ; }, abstract = {In the last couple of decades, biomarkers have been on the rise for diagnostic and predictive value. There has been a rush to identify new markers using new technologies and drug repurposing approaches. SMARCB1 acronym arises from the SWI/SNF (SWItch/Sucrose Non-Fermentable)-related Matrix-associated Actin-dependent Regulator of Chromatin subfamily B member 1 (SMARCB1). It is a molecule, whose role is associated with the sucrose metabolism. SMARCB1 is also called INI1 (Integrase Interactor 1). The molecule was discovered in the mid-1990s. Its role as a loss-of-function marker for malignant rhabdoid tumors (MRT) of renal and extrarenal origin has enormously expanded the spectrum of involved neoplasms since that time. Several tumors have been characterized by genetic aberrations in the SMARCB1 gene. They include reduction in expression, loss of expression, and mosaic expression. Most of the tumors are sarcomas, but a variegated group of tumors with mixed phenotypes has also been delineated. It is well known that the outcome of patients harboring genetic aberrations in the SMARCB1 gene has been poor. Guo et al. reported that reduced SMARCB1 expression occurred in 70% of osteosarcomas. Their data significantly correlated with poor neoadjuvant response. These authors emphasize a shorter progression-free and overall survival of the patients demonstrating an altered expression of this gene. Interestingly, mRNA in silico analysis established that SMARCB1 expression correlates with the response to chemotherapy of osteosarcoma patients, but there was no reliable correlation between SMARCB1 expression level and metastasis, response to neoadjuvant therapy, overall survival, and progression-free survival. The study involved a tissue microarray (TMA) on bone tumors that may limit the full evaluation of the gene expression. Nevertheless, Guo et al.'s study is remarkable. It expands the list of the tumors harboring an altered SMARCB1 gene expression and suggests that this marker should be investigated in every pathology workup for potential predictive value. On the other side, much work needs to be done if we hope that we strive to provide additional therapeutic strategies for osteosarcoma patients with altered SMARCB1 gene expression.}, } @article {pmid35578281, year = {2022}, author = {Samanidis, G and Kanakis, M and Kourelis, G and Kolovou, K and Perreas, K}, title = {Acute renal failure after acute type A aortic dissection repair. Insidious postoperative complication with poor short- and long-term prognosis.}, journal = {Journal of cardiac surgery}, volume = {37}, number = {9}, pages = {2618-2620}, doi = {10.1111/jocs.16613}, pmid = {35578281}, issn = {1540-8191}, mesh = {Acute Disease ; *Acute Kidney Injury/etiology ; *Aortic Dissection/complications/surgery ; Humans ; Postoperative Complications/etiology ; Prognosis ; Retrospective Studies ; Treatment Outcome ; }, abstract = {Acute type A aortic dissection (ATAAD) is a life-threatening aortic disease. Many systems and organs are affected by malperfusion which presents preoperatively and postoperatively. Postoperative acute renal failure after ATAAD constitutes a severe and insidious complication. Acute renal damage is observed in many patients with ATAAD preoperatively and it burdens the renal function postoperatively. Renal replacement therapy represents an additional risk factor for short-, mid-, and long-term outcomes after ATAAD repair. Brown et al.'s present study highlight the clinical significance of this complication. Also, they remind us of the importance of optimizing perioperative renal protective strategies in patients undergoing ATAAD repair.}, } @article {pmid35575973, year = {2022}, author = {Perdrizet, J and Horn, E and Nua, W and Perez-Peralta, J and Nailes, J and Santos, J and Ong-Lim, A}, title = {Response to Gomez et al.'s Letter to the Editor Regarding: "Cost-Effectiveness of the 13-Valent Pneumococcal Conjugate Vaccine (PCV13) Versus Lower-Valent Alternatives in Filipino Infants".}, journal = {Infectious diseases and therapy}, volume = {11}, number = {4}, pages = {1763-1765}, pmid = {35575973}, issn = {2193-8229}, } @article {pmid35573090, year = {2022}, author = {Kleijberg, M and Hilton, R and Ahlberg, BM and Tishelman, C}, title = {Conceptualizing impact in community-based participatory action research to engage communities in end-of-life issues.}, journal = {Palliative care and social practice}, volume = {16}, number = {}, pages = {26323524221095107}, pmid = {35573090}, issn = {2632-3524}, abstract = {BACKGROUND: A health promotion approach to end-of-life (EoL) care is gaining traction internationally. However, there is a lack of evaluations of the impact of this approach, particularly regarding community-based initiatives. Conceptualizations of impact in participatory action research (PAR) may contribute to understanding ways in which impact can be investigated in community-based health promotion approaches to EoL issues. We aim to investigate impact and the process of impact development in our community-based PAR project, Studio DöBra, a Swedish health promotion initiative to engage communities in EoL issues.

METHODS: We do this through a qualitative framework analysis expanding on Banks et al.'s theory of co-impact in PAR, based on longitudinal empirical data of Studio DöBra. Studio DöBra was developed in partnership with a range of community organizations and engaged children (9 years old) and older adults (most 80+) with topics related to dying, death, and loss through arts activities. The analyzed empirical data reflect the perspectives of community-partners and academic partners from interviews and meetings spanning 4.5 years.

FINDINGS: We present a model of impact development consisting of impact on individual and group development, action-oriented impact, and strategy-oriented impact; ways they relate to and evolve from one another; and how they may be affected by contextual influences.

CONCLUSION: Besides contributing to conceptualizations of impact in PAR, findings contribute a community perspective to the limited literature investigating the impact of health promotion initiatives related to EoL issues.}, } @article {pmid35564397, year = {2022}, author = {Hynie, M and Jaimes, A and Oda, A and Rivest-Beauregard, M and Perez Gonzalez, L and Ives, N and Ahmad, F and Kuo, BCH and Arya, N and Bokore, N and McKenzie, K}, title = {Assessing Virtual Mental Health Access for Refugees during the COVID-19 Pandemic Using the Levesque Client-Centered Framework: What Have We Learned and How Will We Plan for the Future?.}, journal = {International journal of environmental research and public health}, volume = {19}, number = {9}, pages = {}, pmid = {35564397}, issn = {1660-4601}, support = {173101//CIHR/Canada ; }, mesh = {*COVID-19/epidemiology ; Canada/epidemiology ; Health Services Accessibility ; Humans ; Mental Health ; Pandemics ; *Refugees/psychology ; }, abstract = {During the COVID-19 pandemic, mental health services rapidly transitioned to virtual care. Although such services can improve access for underserved populations, they may also present unique challenges, especially for refugee newcomers. This study examined the multidimensional nature of access to virtual mental health (VMH) care for refugee newcomers during the COVID-19 pandemic, using Levesque et al.'s Client-Centered Framework for Assessing Access to Health Care. One hundred and eight structured and semi structured interviews were conducted in four Canadian provinces (8 community leaders, 37 newcomer clients, 63 mental health or service providers or managers). Deductive qualitative analysis, based on the Client-Centered Framework, identified several overarching themes: challenges due to the cost and complexity of using technology; comfort for VMH outside clinical settings; sustainability post-COVID-19; and communication and the therapeutic alliance. Mental health organizations, community organizations, and service providers can improve access to (virtual) mental health care for refugee newcomers by addressing cultural and structural barriers, tailoring services, and offering choice and flexibility to newcomers.}, } @article {pmid35550673, year = {2022}, author = {Walker, TWN and Gavazov, K and Guillaume, T and Lambert, T and Mariotte, P and Routh, D and Signarbieux, C and Block, S and Münkemüller, T and Nomoto, H and Crowther, TW and Richter, A and Buttler, A and Alexander, JM}, title = {Lowland plant arrival in alpine ecosystems facilitates a decrease in soil carbon content under experimental climate warming.}, journal = {eLife}, volume = {11}, number = {}, pages = {}, pmid = {35550673}, issn = {2050-084X}, mesh = {Carbon ; Climate Change ; *Ecosystem ; Plants ; *Soil ; Soil Microbiology ; }, abstract = {Climate warming is releasing carbon from soils around the world, constituting a positive climate feedback. Warming is also causing species to expand their ranges into new ecosystems. Yet, in most ecosystems, whether range expanding species will amplify or buffer expected soil carbon loss is unknown. Here, we used two whole-community transplant experiments and a follow-up glasshouse experiment to determine whether the establishment of herbaceous lowland plants in alpine ecosystems influences soil carbon content under warming. We found that warming (transplantation to low elevation) led to a negligible decrease in alpine soil carbon content, but its effects became significant and 52% ± 31% (mean ± 95% confidence intervals) larger after lowland plants were introduced at low density into the ecosystem. We present evidence that decreases in soil carbon content likely occurred via lowland plants increasing rates of root exudation, soil microbial respiration, and CO2 release under warming. Our findings suggest that warming-induced range expansions of herbaceous plants have the potential to alter climate feedbacks from this system, and that plant range expansions among herbaceous communities may be an overlooked mediator of warming effects on carbon dynamics.}, } @article {pmid35535801, year = {2022}, author = {Asif, MK and Ibrahim, N and Khan, IM and Khan, SS and Nambiar, P}, title = {Dental age estimation of Malaysian children: a comparison of two-dimensional versus three-dimensional imaging analyses of the developing root apices.}, journal = {Annals of human biology}, volume = {49}, number = {2}, pages = {109-115}, doi = {10.1080/03014460.2022.2075034}, pmid = {35535801}, issn = {1464-5033}, mesh = {*Age Determination by Teeth/methods ; Asian People ; Child ; Ethnicity ; Humans ; Imaging, Three-Dimensional ; Radiography, Panoramic ; Reproducibility of Results ; }, abstract = {AIM: This study compared the effectiveness of the three-dimensional (3D) cone beam computed tomography (CBCT) method of age estimation developed by Asif et al. with two-dimensional Cameriere's method.

SUBJECTS AND METHODS: CBCT images belonging to 129 Malaysian Chinese and Malay ethnic groups aged 7-14 years were investigated and analysed.

RESULTS: The results indicated a strong correlation between chronological age and the predictor variables for both Cameriere's (r = 0.984) and Asif's (r = 0.988) methods of age estimation. Fisher Z test analysis indicated no statistically significant difference in the correlation values between the two methods. Mean absolute error (MAE) value of 0.613 was observed for Cameriere's and 0.290 was observed for Asif's method.

CONCLUSIONS: The results indicated that the methods of age estimation from both Asif et al. and Cameriere et al. are applicable on Malaysian children. However, Asif et al.'s 3D CBCT method of age estimation resulted in greater accuracy and reliability in estimating chronological age.}, } @article {pmid35528713, year = {2022}, author = {Horgan, J and Horowitz, A}, title = {Refocusing science professional learning: social justice at the heart.}, journal = {Cultural studies of science education}, volume = {17}, number = {3}, pages = {907-913}, pmid = {35528713}, issn = {1871-1502}, abstract = {This paper emerges from a reflection inspired by Kristen A. Searle et al.'s Whiteness at work in the elementary classroom: A case study. Through the lens of Whiteness, the authors explored how a White male elementary teacher, who engaged in an integrated technology professional development, implemented culturally responsive teaching. Unfortunately, the teacher was described as falling short of achieving the pedagogy and practice set out by the professional development. With this, we were left to wonder how the outcome of the study would have differed, if the authors chose to focus on social justice education, rather than make it a companion to their professional development on integrated technology. Therefore, in this piece, we explore how science teacher education, like the one presented in Kristen A. Searle et al.'s work, would look if it prioritized the development of socially just science teachers.}, } @article {pmid35513143, year = {2022}, author = {Beretta-Blanco, A and Carrasco-Letelier, L}, title = {Responses to Alcántara et al.'s (2021) comments.}, journal = {The Science of the total environment}, volume = {837}, number = {}, pages = {155555}, doi = {10.1016/j.scitotenv.2022.155555}, pmid = {35513143}, issn = {1879-1026}, } @article {pmid35508238, year = {2022}, author = {Truchet, DM and Ardusso, MG and Forero-López, AD and Rimondino, GN and Buzzi, NS and Malanca, F and Spetter, CV and Fernández-Severini, MD}, title = {Tracking synthetic microdebris contamination in a highly urbanized estuary through crabs as sentinel species: An ecological trait-based approach.}, journal = {The Science of the total environment}, volume = {837}, number = {}, pages = {155631}, doi = {10.1016/j.scitotenv.2022.155631}, pmid = {35508238}, issn = {1879-1026}, mesh = {Animals ; *Brachyura ; Ecosystem ; Environmental Monitoring/methods ; Estuaries ; Geologic Sediments ; Plastics ; Polyethylenes ; Sentinel Species ; Water ; *Water Pollutants, Chemical/analysis ; }, abstract = {Synthetic microdebris (particles of <5 mm) are a worldwide concern because they can affect the community structure of the aquatic ecosystems, organisms, and even food webs. For the biomonitoring of synthetic microdebris (especially microplastics, MPs), mainly benthic invertebrates are used, but crabs have been less studied in the literature. We studied the synthetic microdebris contamination in water, sediments, and three representative intertidal crabs (Neohelice granulata, Cyrtograpsus angulatus and Leptuca uruguayensis) with different lifestyles from the Bahía Blanca estuary, Argentina. The results obtained show the presence of cotton-polyamide (PA), polyethylene (PE), and polyethylene terephthalate (PET) in surface waters. In sediments, we identified cellulose modified (CE), polyester (PES), polyethylene (PE), and alkyd resin, while in crabs, cotton-PA and CE were the predominant ones. The MPs abundance ranged from 8 to 68 items L[-1] in surface water, from 971 to 2840 items Kg[-1] in sediments, and from 0 to 2.58 items g[-1] ww for the three species of crabs. Besides, paint sheets ranged from 0 to 17 in the total samples, with Cr, Mo, Ti, Pb, Cu, Al, S, Ba and Fe on their surface. There were significant differences between the microdebris abundances in the abiotic matrices but not among crabs species. The ecological traits of the different crabs helped to understand the accumulation of synthetic microdebris, an important characteristic when determining the choice of a good biomonitor.}, } @article {pmid35507295, year = {2023}, author = {Icht, M and Zukerman, G and Ben-Itzchak, E and Ben-David, BM}, title = {Response to McKenzie et al. 2021: Keep It Simple; Young Adults With Autism Spectrum Disorder Without Intellectual Disability Can Process Basic Emotions.}, journal = {Journal of autism and developmental disorders}, volume = {53}, number = {3}, pages = {1269-1272}, pmid = {35507295}, issn = {1573-3432}, mesh = {Humans ; Young Adult ; *Autism Spectrum Disorder/psychology ; *Intellectual Disability ; Emotions/physiology ; Empathy ; *Autistic Disorder ; }, abstract = {We recently read the interesting and informative paper entitled "Empathic accuracy and cognitive and affective empathy in young adults with and without autism spectrum disorder" (McKenzie et al. in Journal of Autism and Developmental Disorders 52: 1-15, 2021). This paper expands recent findings from our lab (Ben-David in Journal of Autism and Developmental Disorders 50: 741-756, 2020a; International Journal of Audiology 60: 319-321, 2020b) and a recent theoretical framework (Icht et al. in Autism Research 14: 1948-1964, 2021) that may suggest a new purview for McKenzie et al.'s results. Namely, these papers suggest that young adults with autism spectrum disorder without intellectual disability can successfully recruit their cognitive abilities to distinguish between different simple spoken emotions, but may still face difficulties processing complex, subtle emotions. McKenzie et al. (Journal of Autism and Developmental Disorders 52: 1-15, 2021) extended these findings to the processing of emotions in video clips, with both visual and auditory information.}, } @article {pmid35504365, year = {2022}, author = {Dell'Oro, M and Short, M and Wilson, P and Peukert, D and Hua, CH and Merchant, TE and Bezak, E}, title = {Lifetime attributable risk of radiation induced second primary cancer from scattering and scanning proton therapy - A model for out-of-field organs of paediatric patients with cranial cancer.}, journal = {Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology}, volume = {172}, number = {}, pages = {65-75}, doi = {10.1016/j.radonc.2022.04.027}, pmid = {35504365}, issn = {1879-0887}, mesh = {Child ; Child, Preschool ; Female ; Humans ; Male ; *Neoplasms, Radiation-Induced/epidemiology/etiology ; *Neoplasms, Second Primary/epidemiology/etiology ; Organs at Risk/radiation effects ; Phantoms, Imaging ; *Proton Therapy/adverse effects ; Radiation Dosage ; Radiotherapy Dosage ; Risk Assessment ; Risk Factors ; }, abstract = {BACKGROUND AND PURPOSE: Proton therapy (PT) can reduce side effects for paediatric cranial malignancies. Despite the high number of paediatric patients treated with PT, radiation induced risk factors for second primary cancer (SPC) in out-of-field organs are unknown. This study estimated lifetime attributable risk (LAR) of SPC as a function of age and sex for out-of-field organs following passive scattering and scanning beam PT in paediatric brain tumours.

MATERIALS AND METHODS: Measured neutron dose equivalent spectra for scattered and scanning PT were sourced from literature. The physical distance of 12 measured organs from paediatric CT dataset-based phantoms (5, 9 and 13 years-of-age) were applied to Schneider et al.'s analytical model using MATLAB (R2020B) to calculate the organ-specific LAR of SPC.

RESULTS: Scanning beam PT demonstrated smaller LAR (per 10,000 person years) of SPC compared to scattering. This was prominent for more radiosensitive organs, including the lung (320 vs 50), breast (1000 vs 150) and thyroid (350 vs 75), but not for all (i.e., rectum and reproductive organs were <10). For most organs, LAR was highest for 5-year-old females (i.e., breast LAR was 1,000 higher than for 13-year-olds), however, outliers existed for distal organs (i.e., stomach and lung).

CONCLUSION: There was large variation in LAR estimates of out-of-field organs based on measured neutron dose equivalents. Younger female cranial paediatric patients were found at higher risk compared to males, especially for passive scattering PT. Not all organs had improved LAR using scanning beam PT for younger age groups.}, } @article {pmid35496650, year = {2022}, author = {Sefcik, JS and Boltz, M and Dellapina, M and Gitlin, LN}, title = {Are Interventions for Formal Caregivers Effective for Improving Dementia Care? A Systematic Review of Systematic Reviews.}, journal = {Innovation in aging}, volume = {6}, number = {2}, pages = {igac005}, pmid = {35496650}, issn = {2399-5300}, support = {K23 NR018673/NR/NINR NIH HHS/United States ; U54 AG063546/AG/NIA NIH HHS/United States ; }, abstract = {BACKGROUND AND OBJECTIVES: Several systematic reviews exist that examine the efficacy of educational interventions in randomized controlled trials (RCTs) designed to improve formal caregivers' knowledge and skills and/or the outcomes of persons living with dementia. The aim of this article is to summarize existing systematic reviews to assess the effectiveness of educational interventions tested in RCTs and directed at formal caregivers.

RESEARCH DESIGN AND METHODS: Smith et al.'s methodology guided this systematic review of systematic reviews. We used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and the A MeaSurement Tool to Assess systematic Reviews 2 (AMSTAR 2) for quality appraisals. Reviews were included if they contained interventions with an RCT design that focused on changing staff behavior and/or practice toward persons living with dementia, in any setting and for any health care discipline.

RESULTS: We identified six systematic reviews, one rated as high-quality on the AMSTAR 2. Most interventions were directed at nursing staff, in long-term care facilities, focused on agitation, and were atheoretical. There is insufficient evidence to guide implementation of currently tested interventions; however, training in communication skills, person-centered care, and dementia-care mapping with supervision show promise for improving agitation.

DISCUSSION AND IMPLICATIONS: There's a critical need for additional research with well-designed RCTs, and clear reporting of protocols and findings to inform the field on how best to train and support the workforce. Although there is no conclusive evidence on what interventions are most effective, it could be argued that providing training using interventions with modest evidence of impact is better than no training at all until the evidence base is strengthened.}, } @article {pmid35483210, year = {2022}, author = {Jackson, J}, title = {"I love the job…" Thriving in nursing: A qualitative interview study with framework analysis.}, journal = {International emergency nursing}, volume = {62}, number = {}, pages = {101172}, doi = {10.1016/j.ienj.2022.101172}, pmid = {35483210}, issn = {1878-013X}, mesh = {*Burnout, Professional/psychology ; Humans ; *Job Satisfaction ; Qualitative Research ; Workplace/psychology ; }, abstract = {BACKGROUND: Burnout is a well-known issue among nurses in critical care settings, including emergency nurses. There are decades of research indicating that emergency nurses experience burnout in their work. However, many nurses have long careers in emergency settings, which suggests that burnout is not the only outcome for nurses. Thriving may also be part of nurses' experiences. The Model of Thriving at Work includes external factors (autonomy, climate of trust and respect, and information sharing) and internal factors (knowledge, personal outlook, and relationships). Thriving is characterized by the concepts of vitality and ongoing learning. Previous researchers suggest that thriving fits with some nurses' experiences, based on validated questionnaires. However, thriving has not been investigated among nurses using interview approaches.

AIMS: This article explores nurses' experiences of thriving and assesses the fit of Spreitzer et al.'s Model of Thriving at Work with nurses' experiences.

STUDY DESIGN: Qualitative interview study, using framework analysis.

METHODS: Eleven nurses, from a single site, completed semi-structured interviews. These interviews explored nurses' workplace experiences, both positive and negative.

RESULTS: Participants reported experiences that fit with the Model of Thriving at Work, consisting of vitality, ongoing learning, and external and internal factors. Nurses hesitated to describe themselves in positive ways, referring instead to being 'not burnt out'. Nurses could, however, readily identify qualities of thriving in others, and viewed those nurses as aspirational. In addition to the Model, participants highlighted their emotional burden, workload, and ethical issues as important contributors to thriving. The Model could potentially be expanded to include these factors.

CONCLUSIONS: Thriving at work could be part of a range of emergency nurses' workplace outcomes. External and internal factors contribute to thriving. Healthcare leaders could support thriving among emergency nurses by fostering a positive work environment.}, } @article {pmid35481294, year = {2022}, author = {Elshohna, M and Tsouklidis, N}, title = {Top 50 Cited Bone Graft Orthopedic Papers.}, journal = {Cureus}, volume = {14}, number = {3}, pages = {e23419}, pmid = {35481294}, issn = {2168-8184}, abstract = {The purpose of this research is to recognize the highest 50 most-mentioned articles in the literature concentrating on bone grafts. That has been accomplished with the use of the Scopus database and the search slogan "bone grafts," and we inquired for the 50 most-cited articles on bone grafting. The study was completed in September 2020. We investigated the articles issued between 1970 and 2020. The articles were organized and classified based on the total number of citations. We appraised the following information relating to each article: first author, year of publication, journal, and title. A total of 1,580 studies matched our search standards, of which the 50 most-cited extended between 1,862 and 403 citations. Seven articles were cited more than 1,000 times. The article by Marx et al. was the maximum-cited article, with 1,862 citations, followed by Younger et al.'s with 1,461 and Giannoudis et al.'s with 1,245. The majority of the studies originated from the United States (n = 30) and were published in the 2000s. Biomaterials was the most regular destination journal (n = 8), followed by the Journal of Bone and Joint Surgery American series (n = 7). A maximum of the articles focused on the different types of bone grafts and their alternatives including bone tissue engineering (n=29). Our investigation of the highest 50 articles linking to bone grafting has emphasized the most significant papers in the field. These cover a wide-ranging variety of topics including types, management, and mechanism of action of bone grafts. To recognize the present treatment guidelines and how the use of bone grafting has grown, it is vital to know the most-cited articles relating to this grafting.}, } @article {pmid35472420, year = {2022}, author = {Bakker, VJ and Finkelstein, ME and D'Elia, J and Doak, DF and Kirkland, S}, title = {Genetically based demographic reconstructions require careful consideration of generation time.}, journal = {Current biology : CB}, volume = {32}, number = {8}, pages = {R356-R357}, doi = {10.1016/j.cub.2022.03.048}, pmid = {35472420}, issn = {1879-0445}, mesh = {Animals ; Demography ; *Falconiformes ; }, abstract = {Bakker et al. use Robinson et al.'s reconstruction of three species of vulture to illustrate how incorrect generation time estimates can yield inaccurate results, underscoring the importance of generation time specification for genetically based reconstructions, especially for comparisons and species of conservation concern.}, } @article {pmid35469251, year = {2022}, author = {Li, SM and Chen, P and Yan, MZ and Du, WS and Guo, R and Luo, T}, title = {Modified Acupotomy versus Percutaneous Release for Trigger Thumb: A Retrospective Study.}, journal = {Journal of pain research}, volume = {15}, number = {}, pages = {1141-1148}, pmid = {35469251}, issn = {1178-7090}, abstract = {BACKGROUND: Acupotomy is now increasingly used for trigger thumb, while recent evidence showed it increased the risk of nerve injury. Based on the close proximity of the neurovascular bundles and the A1 pulley, we designed a modified acupotomy. Given that percutaneous release is the common surgical treatment, this retrospective study aimed to compare the effect and safety of modified acupotomy versus percutaneous release for trigger thumb.

METHODS: This is a retrospective study. All patients with trigger thumb were retrieved in the electronic records of the Department of Pain Medicine at the Beijing Hospital of Traditional Chinese Medicine from January 2016 to September 2018. Both short-term (3 months) and long-term (2 years) outcomes were evaluated using the criteria established through Gilberts et al.'s questionnaire, including triggering, residual pain, stiffness, digital nerve injury, scar, infection and satisfaction. Chi-square test or Fisher's exact test was used to compare differences between two groups.

RESULTS: A total of 305 patients with 334 trigger thumbs treated with either modified acupotomy (n = 194 thumbs) or percutaneous release (n = 140 thumbs) were included. Of them, 221 (72.5%) were female, and the mean age was 56.2 ± 10.0 years. The mean duration of trigger thumb lasted for 7.5 ± 3.6 months. At 3 months, all triggering were alleviated by both therapies. Although more digital nerve injury occurred in the percutaneous release (0 [0%] thumbs vs 5 [3.6%] thumbs, P = 0.012), more residual pain (30 [15.5%] thumbs vs 6 [4.3%] thumbs; rate ratio, 3.61; 95% confidence interval [CI]: 1.54-8.43; P = 0.001) and less satisfaction occurred in the modified acupotomy group. At 2 years, more recurrent triggering, residual pain and digital nerve injury occurred in the percutaneous release group (2 [1.0%] thumbs vs 12 [8.6%] thumbs; rate ratio, 0.12; 95% CI: 0.03-0.53; P = 0.001; 9 [4.6%] thumbs vs 22 [15.7%] thumbs; rate ratio, 0.30; 95% CI: 0.14-0.62 P < 0.001; 0 [0%] thumbs vs 4 [2.9%] thumbs, P = 0.030, respectively). Moreover, satisfaction was significantly better in the modified acupotomy group.

CONCLUSION: The modified acupotomy had better long-term outcomes and satisfaction than the percutaneous release for trigger thumb, although percutaneous release has less residual pain and better satisfaction in the short term. The modified acupotomy is a treatment option for trigger thumb.}, } @article {pmid35465635, year = {2022}, author = {Tharanon, V and Putthipokin, K and Sakthong, P}, title = {Drug-related problems identified during pharmaceutical care interventions in an intensive care unit at a tertiary university hospital.}, journal = {SAGE open medicine}, volume = {10}, number = {}, pages = {20503121221090881}, pmid = {35465635}, issn = {2050-3121}, abstract = {INTRODUCTION: Drug-related problems could potentially worsen the clinical outcomes in critically ill patients. Critically ill patients are generally considered more vulnerable to harm from drug-related problems due to frequent medication-related events and complicated clinical courses. However, drug-related problems identified by on-ward clinical pharmacists in medical intensive care units in Thailand are not well reported. This study reports clinically relevant data with the description of identified problems, common causes of drug-related problems, and pharmacists' interventions performed in real world, so that it may serve as an educational material for pharmacists who implement a pharmaceutical care and participate in medical intensive care units.

METHODS: A retrospective descriptive study was conducted at a tertiary university hospital in Bangkok, Thailand, from January 2015 to December 2020. The drug-related problems were categorized according to Cipolle et al.'s classification. The severity of drug-related problems in this study was rated by modifying the definition of The National Coordinating Council for Medication Error Reporting and Prevention Taxonomy of Medication Error to report harm from drug-related problem-related patient outcomes.

RESULTS: A total of 698 drug-related problems were detected in 374 critically ill patients. The prevalence of drug-related problems occurring in critically ill patients admitted to the medical intensive care unit was 73.9%. The most frequent drug-related problems were dosage too high (27.7%), ineffective drug (17.2%), need for additional drug therapy (15.3%), unnecessary drug therapy (14.6%), dosage too low (14.3%), adverse drug reaction (9.7%), and non-adherence (1.2%). The severity of drug-related problems in the medical intensive care unit was assessed as a drug-related problem with no harm (78.2%). Pharmacists' interventions were advised according to drug-related problem identification to provide personalized pharmacotherapy optimization in critically ill patients.

CONCLUSION: The most frequent drug-related problem identified during pharmaceutical care interventions in the medical intensive care unit at tertiary university hospital is dosage too high. The severity of drug-related problems is mostly determined as drug-related problems with no harm.}, } @article {pmid35463491, year = {2022}, author = {Chiu, YC and Huang, JT and Lee, WK and Lin, CJ and Lin, CH}, title = {Reanalyzing the Maia and McClelland (2004) Empirical Data: How Do Participants Really Behave in the Iowa Gambling Task?.}, journal = {Frontiers in psychiatry}, volume = {13}, number = {}, pages = {788456}, pmid = {35463491}, issn = {1664-0640}, abstract = {BACKGROUND: Since 2007, the Iowa Gambling Task (IGT) has been a standardized clinical assessment tool for assessing decision behavior in 13 psychiatric/neurological conditions. After the publication of Maia and McClelland's (1) article, there were two responses in 2005 from Bechara et al. and Maia and McClelland, respectively, discussing whether implicit emotion or explicit knowledge influences the development of foresighted decision strategies under uncertain circumstances (e.g., as simulated in the IGT).

METHODS AND RESULTS: We reanalyze and verify the data obtained by Maia and McClelland (1) in their study "What participants really know in the Iowa Gambling Task" and find that decision-makers were lured into shortsighted decisions by the prospect of immediate gains and losses.

CONCLUSION: Although the findings of this reanalysis cannot support any arguments concerning the effect of either implicit emotion or explicit knowledge, we find evidence that, based on the gain-loss frequency in the IGT, participants behave myopically. This is consistent with most IGT-related articles (58 out of 86) in Lee et al.'s (2) cross-cultural review. Alternatively, under uncertain circumstances, there is probably no such thing as foresighted decision strategy irrespective of the proposed mechanisms of implicit emotion or explicit knowledge.}, } @article {pmid35460556, year = {2022}, author = {Roncoroni, J and Okun, M and Hudson, A}, title = {Systematic review: sleep health in the US Latinx population.}, journal = {Sleep}, volume = {45}, number = {7}, pages = {}, doi = {10.1093/sleep/zsac092}, pmid = {35460556}, issn = {1550-9109}, mesh = {Adult ; Chronic Disease ; Ethnicity ; Humans ; Middle Aged ; Sleep ; *Sleep Initiation and Maintenance Disorders ; *Sleep Wake Disorders/epidemiology ; United States/epidemiology ; White People ; }, abstract = {Sleep disturbances are a common and unmet health problem in Latinx. While Latinx report similar sleep disturbances as non-Hispanic Whites [NHW], Latinx suffer from these disturbances to a greater degree than their NHW counterparts. Sleep disturbances are associated with increased risk of chronic health conditions, which Latinx experience at high rates. Research also points to significant sleep differences within Latinx. Given that Latinx are a rapidly growing population in the United States, sleep disparities between Latinx and NHWs and sleep differences within Latinx warrant further investigation. While research on Latinx sleep is growing, the last narrative review on US Latinx sleep health was published by Loredo and colleagues in 2010. Our narrative review expands on Loredo et al.'s work, adding the literature on Latinx sleep published since 2010 (N = 70). A total of 78 peer-reviewed articles related to young to middle-aged (i.e., 18-65 years) healthy Latinx adult sleep were identified in three databases-PsycInfo, PubMed/Medline, and Web of Science. With the socioecological model as framework, this review (1) summarizes current evidence pertaining to sleep health in healthy, community dwelling, urban Latinx adults; (2) discusses measurement challenges related to investigating Latinx sleep disparities and differences; and (3) discusses potential contributors to Latinx sleep. The prevalence of short sleep duration, long sleep duration, and poor sleep quality is high among Latinx; there are differences by Latinx subgroup. Our review identifies several multi-level influences associated with poor sleep: SES, sexual minority status, racial discrimination, access to care, neighborhood environment, and shift work. N = 250/250.}, } @article {pmid35450441, year = {2022}, author = {Lebel, S and Dewar, M and Brillon, P}, title = {Translation, validation and exploration of the factor structure in the French version of the Posttraumatic Cognitions Inventory (PTCI).}, journal = {Canadian journal of psychiatry. Revue canadienne de psychiatrie}, volume = {67}, number = {8}, pages = {648-658}, pmid = {35450441}, issn = {1497-0015}, mesh = {Cognition ; Humans ; Psychometrics ; Reproducibility of Results ; *Stress Disorders, Post-Traumatic/diagnosis ; Surveys and Questionnaires ; Translations ; }, abstract = {OBJECTIVES: In order to validate a French version of the PTCI, this study investigates two objectives using two French speaking samples: (1) test 10 factor structures identified in prior studies, and (2) assess the other psychometric properties of the best fitting factor structure.

METHOD: The PTCI was translated in French using a reverse translation method and administered to 202 university students and 114 aid workers. Suitability indexes of the appropriate factor structures previously identified in prior studies were examined. Internal consistency, correlations between subscales and convergent, divergent and discriminant validities in the most appropriate structure were evaluated.

RESULTS: Results support that only Wells et al.'s short 9-item version of the PTCI and three factors shows excellent suitability indexes. This version also outlines an excellent internal consistency and solid convergent, divergent, and discriminant validities.

CONCLUSIONS: This study confirms the empirical validity, fidelity, and utility of Wells et al.'s short version of the PTCI. This is the first PTCI French validation, which is a major advantage when it comes to assess posttraumatic cognitions in French trauma victims.}, } @article {pmid35448954, year = {2022}, author = {Momeni, K and Amani, R and Janjani, P and Majzoobi, MR and Forstmeier, S and Nosrati, P}, title = {Attachment styles and happiness in the elderly: the mediating role of reminiscence styles.}, journal = {BMC geriatrics}, volume = {22}, number = {1}, pages = {349}, pmid = {35448954}, issn = {1471-2318}, mesh = {*Affect ; Aged ; Female ; *Happiness ; Humans ; Iran ; Male ; Memory ; Surveys and Questionnaires ; }, abstract = {BACKGROUND: The current study aims to investigate the relationship between attachment styles and happiness through the mediating role of reminiscence styles in the elderly.

METHODS: This was a correlational study of structural equations modelling (SEM) type. The statistical population included all the elderly aged at least 60 years living in Kermanshah province, Iran in 2021, among whom 380 (182 men and 198 women) were selected using convenience sampling method. Participants filled out the questionnaires of Adult Attachment Styles, Oxford Happiness, and Amani et al.'s Reminiscence Styles.

RESULTS: The results indicated that secure attachment style has a positive and negative relationship with positive reminiscence (PR) and negative reminiscence (NR), respectively. However, the opposite held true for both avoidant and ambivalent attachment styles. It was also found that secure attachment style has a positive relationship, and avoidant and ambivalent attachment styles have a negative relationship with happiness. Moreover, participants' gender and age had no moderating effect on the mentioned relationships. The results of SEM indicated that secure and ambivalent attachment styles were associated with happiness through both PR and NR, and avoidant attachment style was associated with happiness only through NR.

CONCLUSIONS: The findings emphasize the significance of the development of internal working models based on the kind of parent-child's reminiscences and narratives, and the lifelong effects of these models.}, } @article {pmid35444863, year = {2022}, author = {DeYoung, CG and Kotov, R and Krueger, RF and Cicero, DC and Conway, CC and Eaton, NR and Forbes, MK and Hallquist, MN and Jonas, K and Latzman, RD and Rodriguez-Seijas, C and Ruggero, CJ and Simms, LJ and Waldman, ID and Waszczuk, MA and Widiger, T and Wright, AGC}, title = {Answering questions about the Hierarchical Taxonomy of Psychopathology (HiTOP): Analogies to whales and sharks miss the boat.}, journal = {Clinical psychological science : a journal of the Association for Psychological Science}, volume = {10}, number = {2}, pages = {279-284}, pmid = {35444863}, issn = {2167-7026}, support = {R01 MH122537/MH/NIMH NIH HHS/United States ; }, abstract = {This commentary discusses questions and misconceptions about HiTOP raised by Haeffel et al. (2021). We explain what the system classifies and why it is descriptive and atheoretical, highlighting benefits and limitations of this approach. We clarify why the system is organized according to patterns of covariation or comorbidity among signs and symptoms of psychopathology, and we discuss how it is designed to be falsifiable and revised in a manner that is responsive to data. We refer to the body of evidence for HiTOP's external validity and for its scientific and clinical utility. We further describe how the system is currently used in clinics. In sum, many of Haeffel et al.'s concerns about HiTOP are unwarranted, and for those concerns that reflect real current limitations of HiTOP, our consortium is working to address them, with the aim of creating a nosology that is comprehensive and useful to both scientists and clinicians.}, } @article {pmid35441739, year = {2022}, author = {Vaismoradi, M and Fredriksen Moe, C and Ursin, G and Ingstad, K}, title = {Looking through racism in the nurse-patient relationship from the lens of culturally congruent care: A scoping review.}, journal = {Journal of advanced nursing}, volume = {78}, number = {9}, pages = {2665-2677}, pmid = {35441739}, issn = {1365-2648}, mesh = {Culturally Competent Care ; Humans ; Nurse-Patient Relations ; *Occupational Stress ; *Racism ; }, abstract = {AIM: This review aimed to identify the nature of racism in the nurse-patient relationship and summarize international research findings about it.

DESIGN: A scoping review of the international literature.

DATA SOURCES: The search process encompassed three main online databases of PubMed (including MEDLINE), Scopus and Embase, from 2009 until 2021.

REVIEW METHODS: The scoping review was informed by the Levac et al.'s framework to map the research phenomenon and summarize current empirical research findings. Also, the review findings were reflected in the three-dimensional puzzle model of culturally congruent care in the discussion section.

RESULTS: The search process led to retrieving 149 articles, of which 10 studies were entered into data analysis and reporting results. They had variations in the research methodology and the context of the nurse-patient relationship. The thematical analysis of the studies' findings led to the development of three categories as follows: bilateral ignition of racism, hidden and manifest consequences of racism and encountering strategies.

CONCLUSION: Racism threatens patients' and nurses' dignity in the healthcare system. There is a need to develop a framework of action based on the principles of culturally congruent care to eradicate racism from the nurse-patient relationship in the globalized context of healthcare.

IMPACT: Racism in the nurse-patient relationship has remained a relatively unexplored area of the nursing literature. It hinders efforts to meet patients' and families' needs and increases their dissatisfaction with nursing care. Also, racism from patients towards nurses causes emotional trauma and enhances job-related stress among nurses. Further research should be conducted on this culturally variant phenomenon. Also, the participation of patients and nurses should be sought to prohibit racism in healthcare settings.}, } @article {pmid35438635, year = {2022}, author = {Takaine, M and Imamura, H and Yoshida, S}, title = {High and stable ATP levels prevent aberrant intracellular protein aggregation in yeast.}, journal = {eLife}, volume = {11}, number = {}, pages = {}, pmid = {35438635}, issn = {2050-084X}, mesh = {AMP-Activated Protein Kinases/metabolism ; Adenosine Triphosphate/metabolism ; Adenylate Kinase/metabolism ; *Protein Aggregates ; *Saccharomyces cerevisiae/genetics/metabolism ; alpha-Synuclein/genetics/metabolism ; }, abstract = {Adenosine triphosphate (ATP) at millimolar levels has recently been implicated in the solubilization of cellular proteins. However, the significance of this high ATP level under physiological conditions and the mechanisms that maintain ATP remain unclear. We herein demonstrated that AMP-activated protein kinase (AMPK) and adenylate kinase (ADK) cooperated to maintain cellular ATP levels regardless of glucose levels. Single-cell imaging of ATP-reduced yeast mutants revealed that ATP levels in these mutants underwent stochastic and transient depletion, which promoted the cytotoxic aggregation of endogenous proteins and pathogenic proteins, such as huntingtin and α-synuclein. Moreover, pharmacological elevations in ATP levels in an ATP-reduced mutant prevented the accumulation of α-synuclein aggregates and its cytotoxicity. The present study demonstrates that cellular ATP homeostasis ensures proteostasis and revealed that suppressing the high volatility of cellular ATP levels prevented cytotoxic protein aggregation, implying that AMPK and ADK are important factors that prevent proteinopathies, such as neurodegenerative diseases.}, } @article {pmid35437582, year = {2022}, author = {Li, J and Landsbergis, P and Sembajwe, G and Descatha, A and Siegrist, J}, title = {Comments to Moretti Anfossi et al.'s (2022) 'Work Exposures and Development of Cardiovascular Diseases: A Systematic Review': What Is Current Scientific Consensus?.}, journal = {Annals of work exposures and health}, volume = {66}, number = {6}, pages = {822-824}, doi = {10.1093/annweh/wxac026}, pmid = {35437582}, issn = {2398-7316}, mesh = {*Cardiovascular Diseases/epidemiology ; Consensus ; Humans ; *Occupational Exposure ; Systematic Reviews as Topic ; }, } @article {pmid35413918, year = {2022}, author = {Malakoane, B and Heunis, JC and Chikobvu, P and Kigozi, NG and Kruger, WH}, title = {Improving public health sector service delivery in the Free State, South Africa: development of a provincial intervention model.}, journal = {BMC health services research}, volume = {22}, number = {1}, pages = {486}, pmid = {35413918}, issn = {1472-6963}, mesh = {*Delivery of Health Care ; Government Programs ; Humans ; *Public Health ; South Africa ; Workforce ; }, abstract = {BACKGROUND: Public health sector service delivery challenges leading to poor population health outcomes have been observed in the Free State province of South Africa for the past decade. A multi-method situation appraisal of the different functional domains revealed serious health system deficiencies and operational defects, notably fragmentation of healthcare programmes and frontline services, as well as challenges related to governance, accountability and human resources for health. It was therefore necessary to develop a system-wide intervention to comprehensively address defects in the operation of the public health system and its major components.

METHODS: This study describes the development of the 'Health Systems Governance & Accountability' (HSGA) intervention model by the Free State Department of Health (FSDoH) in collaboration with the community and other stakeholders following a participatory action approach. Documented information collected during routine management processes were reviewed for this paper. Starting in March 2013, the development of the HSGA intervention model and the concomitant application of Kaplan and Norton's (1992) Balanced Scorecard performance measurement tool was informed by the World Health Organization's (2007) conceptual framework for health system strengthening and reform comprised of six health system 'building blocks.' The multiple and overlapping processes and actions to develop the intervention are described according to the four steps in Kaplan et al.'s (2013) systems approach to health systems strengthening: (i) problem identification, (ii) description, (iii) alteration and (iv) implementation.

RESULTS: The finalisation of the HSGA intervention model before end-2013 was a prelude to the development of the FSDoH's Strategic Transformation Plan 2015-2030. The HSGA intervention model was used as a tool to implement and integrate the Plan's programmes moving forward with a consistent focus on the six building blocks for health systems strengthening and the all-important linkages between them.

CONCLUSION: The model was developed to address fragmentation and improve public health service delivery by the provincial health department. In January 2016, the intervention model became an official departmental policy, meaning that it was approved for implementation, compliance, monitoring and reporting, and became the guiding framework for health systems strengthening and transform in the Free State.}, } @article {pmid35412544, year = {2022}, author = {Rangel, C and Espinosa-Garcia, J}, title = {Theoretical study of the O([3]P) + SiH4 reaction: global potential energy surface, kinetics and dynamics study.}, journal = {Physical chemistry chemical physics : PCCP}, volume = {24}, number = {16}, pages = {9735-9742}, doi = {10.1039/d2cp00524g}, pmid = {35412544}, issn = {1463-9084}, abstract = {In order to understand the gas-phase hydrogen abstraction reaction between O([3]P) and silane we began by developing the first full-dimensional analytical potential energy surface, named PES-2022. It is basically a valence bond function augmented with molecular mechanic terms describing in an intuitive way stretching and bending nuclei motions, and it is fitted to high level ab initio calculations. The surface presents continuous and smooth behaviour, with analytical first energy derivatives, on which the hydrogen atoms in silane are permutationally symmetric. Based on PES-2022, a kinetics study was performed using the variational transition-state theory with multidimensional tunnelling corrections in the temperature range of 300-1000 K. We observed that experimental and theoretical results show widely spread results, both in absolute value and temperature dependence, possibly because they include the reactivity from both O([3]P) and O([1]D) electronic states, which present different mechanisms and multiple channels. When the comparison is performed on the same footing, O([3]P) + SiH4 → HO + SiH3, the present results agree with Ding and Marshall's experiments and with Zhang et al.'s theoretical rate constants. The kinetic isotope effects (KIEs) reproduced the only experimental value, improving previous theoretical results. Finally, a dynamics study was performed on PES-2022 using quasi-classical trajectory calculations under two different initial conditions, at fixed room temperature and at a fixed collision energy of 8.0 kcal mol[-1]. In the first case, the available energy deposited as HO(v) vibration was 47%, with population inversion, P(v = 0)/P(v = 1) = 11/89%, reproducing the experimental evidence. In the second case, the experimental product translational distribution was reasonably simulated, while the angular product distribution presented opposite behaviour, backward versus forward. On analysing this discrepancy, we found that while in the present work the O([3]P) + SiH4 reaction was reported, in the experiment both O([3]P) and O([1]D) electronic states are reported. So, the comparison was not performed on the same footing. In sum, agreement of the present results with experiments permits us to be reasonably optimistic about the quality and accuracy of the new PES, and at the same time to highlight the fact that theory/experiment comparisons must be performed on the same footing.}, } @article {pmid35408092, year = {2022}, author = {Jin, S and Johansson, P and Kim, H and Hong, S}, title = {Enhancing Time-Frequency Analysis with Zero-Mean Preprocessing.}, journal = {Sensors (Basel, Switzerland)}, volume = {22}, number = {7}, pages = {}, pmid = {35408092}, issn = {1424-8220}, support = {2020M3F3A2A01082591//National Research Foundation of Korea/ ; }, mesh = {*Computer Security ; *Software ; }, abstract = {Side-channel analysis is a critical threat to cryptosystems on the Internet of Things and in relation to embedded devices, and appropriate side-channel countermeasure must be required for physical security. A combined countermeasure approach employing first-order masking and desynchronization simultaneously is a general and cost-efficient approach to counteracting side-channel analysis. With the development of side-channel countermeasures, there are plenty of advanced attacks introduced to defeat such countermeasures. At CARDIS 2013, Belgarric et al. first proposed time-frequency analysis, a promising attack regarding the complexity of computation and memory compared to other attacks, such as conventional second-order side-channel analysis after synchronization. Nevertheless, their time-frequency analysis seems to have lower performance than expected against some datasets protected by combined countermeasures. It is therefore required to study the factors that affect the performance of time-frequency analysis. In this paper, we investigate Belgarric et al.'s time-frequency analysis and conduct a mathematical analysis in regard to the preprocessing of frequency information for second-order side-channel analysis. Based on this analysis, we claim that zero-mean preprocessing enhances the performance of time-frequency analysis. We verify that our analysis is valid through experimental results from two datasets, which are different types of first-order masked Advanced Encryption Standard (AES) software implementations. The experimental results show that time-frequency analysis with zero-mean preprocessing seems to have an enhanced or complementary performance compared to the analysis without preprocessing.}, } @article {pmid35397417, year = {2022}, author = {Curley, CM and Johnson, BT}, title = {Sexuality and aging: Is it time for a new sexual revolution?.}, journal = {Social science & medicine (1982)}, volume = {301}, number = {}, pages = {114865}, doi = {10.1016/j.socscimed.2022.114865}, pmid = {35397417}, issn = {1873-5347}, mesh = {Aged ; *Ageism ; Aging ; Humans ; Sexual Behavior ; *Sexual Dysfunction, Physiological ; Sexuality ; }, abstract = {People in Western cultures live increasingly longer, and medical advancements, health care availability, and lifestyle changes have widened the possibilities of continued sexuality, sexual activity, and sexual diversity well into older adulthood. Yet, research studies have mainly eschewed discussions of sexual possibilities. Although studies have examined the benefits of sexual activity, often they focus purely on sexual function and sexual dysfunction, physical limitations, and the practicalities (such as finding a partner) of sex as persons age. This commentary posits that, in many instances, the social constraints around aging and sexuality inhibit sexuality in older adults in ways that may be more significant than functional or practical limitations. Portrayals in the media either reinforce social norms of the asexual older adult or portray images of the "sexy oldie" that may be unattainable for many older adults. We provide a brief review of sexuality research and prevailing sexual social norms. As Towler et al.'s (2021) elaborate study illustrates, many sexually active older adults struggle with ageism, stigma, and shame arising from the perceived social unacceptability of their sexuality. Studies of older adults from other Western countries reveal similar stories. Accordingly, achieving sexual well-being may be more dependent on changing social norms around sexuality and aging than on discovering new arousal medication to treat physical limitations. Moreover, we advocate for changing the social and academic dialogue from successful aging, which requires maintaining health and vitality-to the aging experience, which incorporates aspects of positive aging such as sexual wisdom, sexual experience, and the sexual diversity that comes with older adulthood. This "new sexual revolution" would elevate sexuality and aging as socially admirable and desirable.}, } @article {pmid35392709, year = {2022}, author = {Doe, MJ}, title = {Nursing Ethics Embedded in Nursing Theoretical Frameworks.}, journal = {Nursing science quarterly}, volume = {35}, number = {2}, pages = {270-272}, doi = {10.1177/08943184211070579}, pmid = {35392709}, issn = {1552-7409}, mesh = {*Education, Nursing ; *Ethics, Nursing ; Humans ; }, abstract = {This author reviews and provides an introduction to Glasgow et al.'s Legal and Ethical Issues in Nursing Education: An Essential Guide. Moreover, the author shares further insight about nursing ethics embedded in nursing theoretical frameworks.}, } @article {pmid35391659, year = {2022}, author = {Han, T and Proctor, RW}, title = {Revisiting variable-foreperiod effects: evaluating the repetition priming account.}, journal = {Attention, perception & psychophysics}, volume = {84}, number = {4}, pages = {1193-1207}, pmid = {35391659}, issn = {1943-393X}, mesh = {*Cognition ; Humans ; Reaction Time/physiology ; *Repetition Priming ; }, abstract = {A warning signal preceding an imperative stimulus by a certain foreperiod can accelerate responses (foreperiod effect). When foreperiod is varied within a block, the foreperiod effect on reaction time (RT) is modulated by both the current and the prior foreperiods. Using a non-aging foreperiod distribution in a simple-reaction task, Capizzi et al. (Cognition, 134, 39-49, 2015) found equal sequential effects for different foreperiods, which they credited to repetition priming. The multiple-trace theory of Los et al. (Frontiers in Psychology, 5, Article 1058, 2014) attributes the slope of the foreperiod-RT function to the foreperiod distribution. We conducted three experiments that examined these predicted relations. Experiment 1 tested Capizzi et al.'s prediction in a choice-reaction task and found an increasing foreperiod-RT function but a larger sequential effect at the shorter foreperiod. Experiment 2 used two distinct short foreperiods with the same foreperiod distribution and found a decreasing foreperiod-RT function. By increasing the difference between the foreperiods used in Experiment 2, Experiment 3 yielded a larger sequential effect overall. The experiments provide evidence that, with a non-aging foreperiod distribution, the variable-foreperiod paradigm yields unequal sequential-effect sizes at the different foreperiods, consistent with the multiple-trace theory but contrary to Capizzi et al.'s repetition-priming account. The foreperiod-RT functions are similar to those of the fixed-foreperiod paradigm, which is not predicted by the multiple trace theory.}, } @article {pmid35389702, year = {2022}, author = {Yang, H and Taikh, A and Lupker, SJ}, title = {A reexamination of the impact of morphology on transposed character priming effects.}, journal = {Journal of experimental psychology. Learning, memory, and cognition}, volume = {48}, number = {6}, pages = {785-797}, doi = {10.1037/xlm0001119}, pmid = {35389702}, issn = {1939-1285}, support = {//Zhejiang Provincial Philosophy and Social Science Planning Project/ ; //Natural Sciences and Engineering Research Council/ ; }, mesh = {Humans ; Motor Activity ; *Pattern Recognition, Visual/physiology ; *Reading ; }, abstract = {Using two-character Chinese word targets in a masked priming lexical-decision task, Gu and colleagues (2015) demonstrated a significant transposed character (TC) priming effect. More importantly, the priming effect was the same size for single-morpheme words and multiple-morpheme words, suggesting that TC priming effects are not influenced by morphemic structure. In Chinese, there are, however, two types of single-morpheme words, single-morpheme simple words (e.g., [similar to practice in English]) and single-morpheme complex words (e.g., [similar to carpet in English in that both components are words themselves and, hence, when presented in transposed order, may activate morphological information reflecting the individual components rather than the word itself]), a contrast that Gu et al. did not examine. In Experiment 1, we replicated Gu et al.'s finding of equal TC priming effects for their single- and multiple-morpheme words, although our priming effects were noticeably smaller than theirs. In Experiment 2, we split the single-morpheme condition in order to examine the TC priming effects for single-morpheme simple words, single-morpheme complex words and multiple-morpheme words. The results showed that the single-morpheme complex words produced the smallest priming effect, indicating that transposed morphemes can influence masked priming in Chinese; however, apparently only in an inhibitory fashion. (PsycInfo Database Record (c) 2022 APA, all rights reserved).}, } @article {pmid35386830, year = {2022}, author = {Hadfield, JD and Reed, TE}, title = {Directional selection and the evolution of breeding date in birds, revisited: Hard selection and the evolution of plasticity.}, journal = {Evolution letters}, volume = {6}, number = {2}, pages = {178-188}, pmid = {35386830}, issn = {2056-3744}, abstract = {The mismatch between when individuals breed and when we think they should breed has been a long-standing problem in evolutionary ecology. Price et al. is a classic theory paper in this field and is mainly cited for its most obvious result: if individuals with high nutritional condition breed early, then the advantage of breeding early may be overestimated when information on nutritional condition is absent. Price at al.'s less obvious result is that individuals, on average, are expected to breed later than the optimum. Here, we provide an explanation of their non-intuitive result in terms of hard selection, and go on to show that neither of their results are expected to hold if the relationship between breeding date and nutrition is allowed to evolve. By introducing the assumption that the advantage of breeding early is greater for individuals in high nutritional condition, we show that their most cited result can be salvaged. However, individuals, on average, are expected to breed earlier than the optimum, not later. More generally, we also show that the hard selection mechanisms that underpin these results have major implications for the evolution of plasticity: when environmental heterogeneity becomes too great, plasticity is selected against, prohibiting the evolution of generalists.}, } @article {pmid35385128, year = {2022}, author = {Utkin, A and Ermolova, L and Utkina, I and Dulepova, N and Rosbakh, S}, title = {Utkin et al.'s dataset on specific leaf area.}, journal = {Ecology}, volume = {103}, number = {7}, pages = {e3714}, doi = {10.1002/ecy.3714}, pmid = {35385128}, issn = {1939-9170}, mesh = {*Forests ; Humans ; Plant Development ; *Plant Leaves/physiology ; Plants ; }, abstract = {Specific leaf area (SLA; one-sided leaf area per unit of dry mass) is a key trait indicating plant growth strategy and its responses to changing environments. Despite its high relevance for ecological research and recent efforts to mobilize the trait data, information on SLA in many plant lineages and biogeographic regions is still underrepresented. To assist in closing this gap, we translated and digitized a large dataset on SLA titled the Surface areas of forest plants by Anatoly I. Utikin, Lyudmila S. Ermolova, and Irina A. Utkina, published in Russian in 2008 (Nakua, Moscow, Russia) and previously not accessible to the great majority of people in the international research community. The book contains a compendium of SLA values collected by A. Utkin and his colleagues published between 1918 and 2006 containing research on ~1100 gymnosperm species from 562 genera and 139 families. Additionally, Utkin et al. provided useful information on the SLA ranges and SLA responses to changing illumination for several species. Also, the dataset contains ~200 references to research on SLA conducted between 1918 and 2006. The dataset is ready to use in various trait analyses. There are no copyright or proprietary restrictions for research or teaching purposes. The authors would appreciate notification when and how the data are used.}, } @article {pmid35363607, year = {2022}, author = {Verma, R and Kumar, N and Patil, A and Kurian, NC and Rane, S and Sethi, A}, title = {Author's Reply to "MoNuSAC2020: A Multi-Organ Nuclei Segmentation and Classification Challenge".}, journal = {IEEE transactions on medical imaging}, volume = {41}, number = {4}, pages = {1000-1003}, doi = {10.1109/TMI.2022.3157048}, pmid = {35363607}, issn = {1558-254X}, mesh = {*Cell Nucleus ; *Histological Techniques ; Humans ; }, abstract = {We had released MoNuSAC2020 as one of the largest publicly available, manually annotated, curated, multi-class, and multi-instance medical image segmentation datasets. Based on this dataset, we had organized a challenge at the International Symposium on Biomedical Imaging (ISBI) 2020. Along with the challenge participants, we had published an article summarizing the results and findings of the challenge (Verma et al., 2021). Foucart et al. (2022) in their "Analysis of the MoNuSAC 2020 challenge evaluation and results: metric implementation errors" have pointed ways in which the computation of the segmentation performance metric for the challenge can be corrected or improved. After a careful examination of their analysis, we have found a small bug in our code and an erroneous column-header swap in one of our result tables. Here, we present our response to their analysis, and issue an errata. After fixing the bug the challenge rankings remain largely unaffected. On the other hand, two of Foucart et al.'s other suggestions are good for future consideration, but it is not clear that those should be immediately implemented. We thank Foucart et al. for their detailed analysis to help us fix the two errors.}, } @article {pmid35362928, year = {2022}, author = {Gallagher, S}, title = {Response-An Extreme Ordeal: Writing Emotion in Qualitative Research.}, journal = {Journal of bioethical inquiry}, volume = {19}, number = {1}, pages = {101-108}, pmid = {35362928}, issn = {1872-4353}, mesh = {Emotions ; *Hematopoietic Stem Cell Transplantation ; Humans ; Qualitative Research ; Transplantation, Autologous ; Writing ; }, abstract = {Responding to the stimulus afforded by Little et al.'s "Pragmatic pluralism: Mutual tolerance of contested understandings between orthodox and alternative practitioners in autologous stem cell transplantation," this paper explores how the norms of qualitative inquiry affect the representation of emotion in research reports. It describes a conflict between the construction of emotion in qualitative research accounts and its application to analysis and theorization, whose origins may lie in researchers' reticence when it comes to conveying or using the emotional features of data. The technical aspects of report writing that are associated with this conflict are explored via a deconstruction of Little et al.'s paper and a survey of the qualitative research methods literature. Writing to convey emotion and analysing to include author-constructed emotional context are neglected topics. Using data in Little et al.'s text, the paper demonstrates the importance of author-constructed emotional context to theory generation. The paper recommends the inclusion of emotional context as data in analysis and points to lessons Little et al.'s paper offers in the areas of narrative technique and reflexive practice.}, } @article {pmid35360793, year = {2022}, author = {Agarwal, N and Jain, P and Khan, TN and Gupta, R}, title = {Chest radiographic findings and their correlation with disease progression in COVID-19 patients in northern India.}, journal = {Journal of family medicine and primary care}, volume = {11}, number = {2}, pages = {559-566}, pmid = {35360793}, issn = {2249-4863}, abstract = {INTRODUCTION: The present study was undertaken to describe and quantify the spectrum of radiographic findings on coronavirus disease 2019 (COVID-19) patients. The study also aimed to analyse the changes in chest X-ray (CXR) with disease progression.

METHODS: COVID-19 patients admitted between the period of 15 March 2020 and 1 July 2020 were retrospectively enrolled. CXR images were assessed and reported as 'Normal' or 'Abnormal'. A severity score was calculated using Warren et al.'s Radiographic Assessment of Lung Edema scoring. Correlations of the severity score thus calculated were sought with age, sex, clinical manifestations and presence of comorbidities.

RESULTS: Five hundred patients (342 males, 158 females) were enrolled, median age being 35 years. Fever and cough were the most common symptoms but significant correlation of an abnormal CXR was found with dyspnoea. CXRs were normal in 67% and abnormal in 33% patients. The commonest comorbidities were diabetes mellitus and cardiovascular disease including hypertension, coronary artery disease and congestive heart failure. Predominant pattern was ground glass opacities, reticular alteration and consolidation peaking in the second week from symptom onset. The most frequent distribution was bilateral, peripheral with middle/lower predominance. Increasing age, male sex, presence of dyspnoea and comorbidities correlated with abnormal findings on CXR. Critical illness and mortality correlated strongly with increasing age, male sex and presence of dyspnoea, less so with presence of comorbidities.

CONCLUSION: In the current scenario with clinicians and radiologists working in tandem, CXR seems to be a promising tool in providing relevant information in a simplified way.}, } @article {pmid35357857, year = {2022}, author = {Christensen, KA and Hagan, KE and Forbush, KT}, title = {Clinical science can address rising eating disorder psychopathology during the COVID-19 pandemic: Comment on Gruber et al. (2020).}, journal = {The American psychologist}, volume = {77}, number = {1}, pages = {140-142}, pmid = {35357857}, issn = {1935-990X}, support = {R21 AG073892/AG/NIA NIH HHS/United States ; T32 MH096679/MH/NIMH NIH HHS/United States ; TL1 TR002368/TR/NCATS NIH HHS/United States ; }, mesh = {*COVID-19 ; *Feeding and Eating Disorders/epidemiology/therapy ; Female ; Humans ; Male ; Pandemics ; Prevalence ; Psychopathology ; }, abstract = {Eating disorders (EDs) are serious psychiatric disorders that affect 13%-18% of young men and women. EDs are associated with substantial psychiatric and medical morbidity and mortality, indicating a critical need for improved identification and treatment. Despite the relatively high prevalence and severity of EDs, they are often omitted from discussions of mental health. This comment is in response to Gruber et al. (2020), who wrote an important article on the challenges and opportunities facing clinical scientists in the time of COVID-19. Our response extends Gruber et al.'s article by noting additional challenges facing people with an ED during COVID-19 and recognizing opportunities for improved evidence-based assessment and treatment of this important population. (PsycInfo Database Record (c) 2022 APA, all rights reserved).}, } @article {pmid35357854, year = {2022}, author = {Orth, U and Robins, RW}, title = {The benefits of self-esteem: Reply to Krueger et al. (2022) and Brummelman (2022).}, journal = {The American psychologist}, volume = {77}, number = {1}, pages = {23-25}, pmid = {35357854}, issn = {1935-990X}, support = {R01 AG060164/AG/NIA NIH HHS/United States ; U01 AG060164/AG/NIA NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Child ; Humans ; *Interpersonal Relations ; Longitudinal Studies ; Mental Health ; Schools ; *Self Concept ; }, abstract = {Krueger et al. (2022) argue that our review (Orth & Robins, 2022) finds benefits of self-esteem primarily for subjective outcomes and largely fails to demonstrate any "objective" benefits. We disagree with this portrayal of the findings and highlight research that provides evidence for the benefits of self-esteem using objective measures. We also address Krueger et al.'s claim that positivity bias in self-reports can account for the effects of self-esteem on subjectively assessed life outcomes, and explain how the statistical analyses used to document these effects substantially control for this bias. We maintain that there is now a large body of evidence from meta-analyses and large-scale longitudinal studies demonstrating that high self-esteem has adaptive consequences for social relationships, school, work, mental health, physical health, and antisocial behavior. Brummelman (2022) presents a compelling theoretical framework that can guide the design of interventions to improve children's self-esteem. We agree with his concerns about the need for randomized controlled trials to evaluate the efficacy of self-esteem interventions and the importance of ensuring that children's self-esteem can be raised without causing them to become narcissistic. The research reviewed in our article indicates that high self-esteem is adaptive for children, adolescents, and adults, suggesting that well-designed and effective self-esteem interventions might be beneficial for individuals of all ages. (PsycInfo Database Record (c) 2022 APA, all rights reserved).}, } @article {pmid35356589, year = {2022}, author = {Hooghiemstra, H and Cleef, AM and Flantua, SGA}, title = {A paleoecological context to assess the development of oak forest in Colombia: A comment on Zorilla-Azcué, S., Gonzalez-Rodríguez, A., Oyama, K., González, M.A., & Rodríguez-Correa, H., The DNA history of a lonely oak: Quercus humboldtii phylogeography in the Colombian Andes. Ecology and Evolution 2021, doi: 10.100-2/ece3.7529.}, journal = {Ecology and evolution}, volume = {12}, number = {3}, pages = {e8702}, pmid = {35356589}, issn = {2045-7758}, abstract = {The present "comment" on Zorilla-Azcué et al.'s paper "The DNA history of a lonely oak: Quercus humboldtii phylogeography in the Colombian Andes. Ecology and Evolution 2021, doi:10.100-2/ece3.7529" provides the paleoecological understanding of oak forest since Quercus became apparent in the Northern Andes three glacial-interglacial cycles ago. The interpretation of phylogeographical data is placed in an up-to-date paleoecological context. We arrived at sharper conclusions how genetic diversity between Q. humboldtii populations might have been driven by the dynamic environmental theatre of the recent Pleistocene. This paleoecological context also serves the potential future analyses of other arboreal taxa from the Andean montane forest belt. We show that hypotheses to be tested should grow out of phylogenetic analysis and paleoecological understanding together.}, } @article {pmid35352678, year = {2022}, author = {Zhang, Y and Li, M and Yu, B and Lu, S and Zhang, L and Zhu, S and Yu, Z and Xia, T and Huang, H and Jiang, W and Zhang, S and Sun, L and Ye, Q and Sun, J and Zhu, H and Huang, P and Hong, H and Yu, S and Li, W and Ai, D and Fan, J and Li, W and Song, H and Xu, L and Chen, X and Chen, T and Zhou, M and Ou, J and Yang, J and Li, W and Hu, Y and Wu, W}, title = {Cold protection allows local cryotherapy in a clinical-relevant model of traumatic optic neuropathy.}, journal = {eLife}, volume = {11}, number = {}, pages = {}, pmid = {35352678}, issn = {2050-084X}, support = {P30 EY026877/EY/NEI NIH HHS/United States ; R01 EY023295/EY/NEI NIH HHS/United States ; R01 EY024932/EY/NEI NIH HHS/United States ; R01 EY028106/EY/NEI NIH HHS/United States ; }, mesh = {Animals ; Cold Temperature ; *Hypothermia ; *Hypothermia, Induced/methods ; Optic Nerve ; *Optic Nerve Injuries/therapy ; }, abstract = {Therapeutic hypothermia (TH) is potentially an important therapy for central nervous system (CNS) trauma. However, its clinical application remains controversial, hampered by two major factors: (1) Many of the CNS injury sites, such as the optic nerve (ON), are deeply buried, preventing access for local TH. The alternative is to apply TH systemically, which significantly limits the applicable temperature range. (2) Even with possible access for 'local refrigeration', cold-induced cellular damage offsets the benefit of TH. Here we present a clinically translatable model of traumatic optic neuropathy (TON) by applying clinical trans-nasal endoscopic surgery to goats and non-human primates. This model faithfully recapitulates clinical features of TON such as the injury site (pre-chiasmatic ON), the spatiotemporal pattern of neural degeneration, and the accessibility of local treatments with large operating space. We also developed a computer program to simplify the endoscopic procedure and expand this model to other large animal species. Moreover, applying a cold-protective treatment, inspired by our previous hibernation research, enables us to deliver deep hypothermia (4 °C) locally to mitigate inflammation and metabolic stress (indicated by the transcriptomic changes after injury) without cold-induced cellular damage, and confers prominent neuroprotection both structurally and functionally. Intriguingly, neither treatment alone was effective, demonstrating that in situ deep hypothermia combined with cold protection constitutes a breakthrough for TH as a therapy for TON and other CNS traumas.}, } @article {pmid35344777, year = {2022}, author = {Kracht, CL and Staiano, AE}, title = {Thinking inside the box: The future of young children's physical activity and the home environment.}, journal = {Social science & medicine (1982)}, volume = {301}, number = {}, pages = {114930}, pmid = {35344777}, issn = {1873-5347}, support = {T32 DK064584/DK/NIDDK NIH HHS/United States ; U54 GM104940/GM/NIGMS NIH HHS/United States ; }, mesh = {Child ; Child, Preschool ; *Exercise ; Family ; *Home Environment ; Humans ; Policy ; }, abstract = {Parrish et al.'s (2021) investigation of caregiver perceptions of preschoolers' physical activity (PA) within the home environment posits important opportunities for public policy to consider space and available opportunities for PA for preschoolers. This study uncovered qualitative themes on preschoolers' PA in the home, referencing the use of indoor and outdoor spaces, adaptations within the home, interplay between space and caregiving, and variability in child's PA. This work sparks a discussion into the current understanding of the home environment for preschooler PA and future research directions. We propose three main areas to bring forward physical activity and public health research, including 1) role of policies and community (e.g., societal norms) on the home environment and child physical activity, 2) reimagination of the home environment beyond the physical components as a complex system, and 3) advanced measurement of child physical activity using modern technology. Merging these new opportunities with past efforts may help design and facilitate healthier PA and movement patterns for preschoolers now and into the future.}, } @article {pmid35337611, year = {2022}, author = {Lim, ML and van Schooten, KS and Radford, KA and Delbaere, K}, title = {Development and initial validation of the falls health literacy scale.}, journal = {Maturitas}, volume = {159}, number = {}, pages = {40-45}, doi = {10.1016/j.maturitas.2021.12.002}, pmid = {35337611}, issn = {1873-4111}, mesh = {Accidental Falls/prevention & control ; Adolescent ; Adult ; Aged ; Educational Status ; Factor Analysis, Statistical ; *Health Literacy ; Humans ; Reproducibility of Results ; }, abstract = {OBJECTIVES: (i) To develop the Falls Health Literacy Scale (FHLS), a health literacy tool specific to falls, (ii) to evaluate the FHLS's construct validity towards differentiating individuals with different fall-related health literacy, and (iii) to determine its reliability, construct validity and structure in an older population.

METHODS: The initial FHLS, developed based on Sørensen et al.'s health literacy model, was first administered to 144 participants aged ≥18 years for feedback and scale improvement and preliminary analysis to determine the FHLS's construct validity in identifying individuals with different fall-related health literacy. After scale refinement, the FHLS was validated in 227 community-living people aged ≥65 years.

RESULTS: Adult participants with more fall prevention knowledge scored higher on the initial FHLS than those with less fall prevention knowledge (p≤0.001). The final FHLS includes a 25-item subjective and a 14-item objective scale. Older people with ≥1 fall in the past year reported lower FHLS-subjective scores than those who had no falls (Cohen's [d]=0.29, confidence interval [CI]:0.03-0.56, p=0.03). Older people with lower levels of education had lower FHLS-objective scores than their more educated counterparts (d=0.51, CI:0.38-1.43, p≤0.001). Factor analysis of the FHLS-subjective generated six subscales, with CFA showing adequate model fit (RMSEA=0.077, CFI=0.883 and χ2/df =2.35). FHLS-subjective (25-item) showed good reliability, with Cronbach's alpha=0.93, mean inter-item correlation=0.34 (range -0.03-0.81) and intra-class coefficient =0.86 (95% CI:0.69-0.93).

CONCLUSION: The novel, context-specific FHLS displayed good construct validity and reliability. The FHLS holds promise as a screening tool to differentiate individuals with different degrees of fall-related health literacy, which may help guide fall prevention interventions.}, } @article {pmid35332262, year = {2022}, author = {Hong, L and Shi, ZF and Li, KK and Wang, WW and Yang, RR and Kwan, JS and Chen, H and Li, FC and Liu, XZ and Chan, DT and Li, WC and Zhang, ZY and Mao, Y and Ng, HK}, title = {Molecular landscape of pediatric type IDH wildtype, H3 wildtype hemispheric glioblastomas.}, journal = {Laboratory investigation; a journal of technical methods and pathology}, volume = {102}, number = {7}, pages = {731-740}, pmid = {35332262}, issn = {1530-0307}, mesh = {*Brain Neoplasms/pathology ; Child ; ErbB Receptors/genetics ; *Glioblastoma ; Humans ; Mutation ; N-Myc Proto-Oncogene Protein/genetics ; Protein-Tyrosine Kinases/genetics ; Proto-Oncogene Proteins/genetics ; }, abstract = {The WHO (2021) Classification classified a group of pediatric-type high-grade gliomas as IDH wildtype, H3 wildtype but as of currently, they are characterized only by negative molecular features of IDH and H3. We recruited 35 cases of pediatric IDH wildtype and H3 wildtype hemispheric glioblastomas. We evaluated them with genome-wide methylation profiling, targeted sequencing, RNAseq, TERT promoter sequencing, and FISH. The median survival of the cohort was 27.6 months. With Capper et al.'s[36] methylation groups as a map, the cases were found to be epigenetically heterogeneous and were clustered in proximity or overlay of methylation groups PXA-like (n = 8), LGG-like (n = 10), GBM_MYCN (n = 9), GBM_midline (n = 5), and GBM_RTKIII (n = 3). Histology of the tumors in these groups was not different from regular glioblastomas. Methylation groups were not associated with OS. We were unable to identify groups specifically characterized by EGFR or PDGFRA amplification as proposed by other authors. EGFR, PDGFRA, and MYCN amplifications were not correlated with OS. 4/9 cases of the GBM_MYCN cluster did not show MYCN amplification; the group was also enriched for EGFR amplification (4/9 cases) and the two biomarkers overlapped in two cases. Overall, PDGFRA amplification was found in only four cases and they were not restricted to any groups. Cases in proximity to GBM_midline were all hemispheric and showed loss of H3K27me3 staining. Fusion genes ALK/NTRK/ROS1/MET characteristic of infantile glioblastomas were not identified in 17 cases successfully sequenced. BRAF V600E was only found in the PXA group but CDKN2A deletion could be found in other methylation groups. PXA-like cases did not show PXA histological features similar to findings by other authors. No case showed TERT promoter mutation. Mutations of mismatch repair (MMR) genes were poor prognosticators in single (p ≤ 0.001) but not in multivariate analyses (p = 0.229). MGMT had no survival significance in this cohort. Of the other common biomarkers, only TP53 and ATRX mutations were significant poor prognosticators and only TP53 mutation was significant after multivariate analyses (p = 0.024). We conclude that IDH wildtype, H3 wildtype pediatric hemispheric glioblastomas are molecularly heterogeneous and in routine practice, TP53, ATRX, and MMR status could profitably be screened for risk stratification in laboratories without ready access to methylation profiling.}, } @article {pmid35319416, year = {2022}, author = {Pennartz, CMA}, title = {What is exactly the problem with panpsychism?.}, journal = {The Behavioral and brain sciences}, volume = {45}, number = {}, pages = {e57}, doi = {10.1017/S0140525X21001916}, pmid = {35319416}, issn = {1469-1825}, mesh = {*Consciousness ; Humans ; }, abstract = {Merker et al.'s critique calls for a deeper analysis of panpsychism. In principle, the concept of integrated information can be applied to photodiodes and subatomic particles, but I suggest the main obstacle is the lack of any evidence to confirm the presence of consciousness. Also MRW's perspectivalist theory illustrates the difficulties in synthesizing a full-fledged theory of consciousness.}, } @article {pmid35296327, year = {2022}, author = {Mathisen, TS and Eilertsen, G and Ormstad, H and Falkenberg, HK}, title = {'If we don't assess the patient's vision, we risk starting at the wrong end': a qualitative evaluation of a stroke service knowledge translation project.}, journal = {BMC health services research}, volume = {22}, number = {1}, pages = {351}, pmid = {35296327}, issn = {1472-6963}, mesh = {*Activities of Daily Living ; Humans ; Quality of Life ; *Stroke/complications ; Translational Science, Biomedical ; Vision Disorders/diagnosis ; }, abstract = {BACKGROUND: Visual impairments (VIs) affect 60% of stroke survivors and have negative consequences for rehabilitation and quality of life poststroke. Symptoms of VIs post stroke are difficult to identify for stroke survivors and health care professionals without using a structured vision assessment. In this study, we qualitatively evaluate the implementation outcomes after implementing a structured visual assessment with the Competence, Rehabilitation of Sight after Stroke Vision (KROSS) assessment tool in stroke care services.

METHODS: This is a qualitative study comprising four focus group interviews. The health care personnel (HCP) involved in the implementation or with experience using the KROSS assessment tool in practice were invited to participate. We used Proctor et al.'s definitions of implementation outcomes as a framework, which informed the interview guide and analysis. We used a deductive - inductive content analysis, as described by Elo and Kyngäs.

RESULTS: The participants found the structured vision assessment with the KROSS tool as being acceptable; they expressed a motivation and intention to use the new routine in practice. They believed it was important to assess their patient's visual function because it influenced other rehabilitation activities and activities of daily living. Most of the participants reported having adopted the vision assessment in their practice, except for those participants from the home care services who experienced that they have few stroke survivors to follow up on. The assessment was believed to be more appropriate to perform within the rehabilitation services where there is more of a focus on functional assessments. Although vision assessment was new to all the participants, they felt that they improved their vision assessment skills by regularly using the assessment tool. Together with sufficient instructions and supervision, they believed that vison assessment was feasible for their practise. Including the vison assessment in the existing routines and systems was important to promote sustainable implementation.

CONCLUSION: Implementing a structured vision assessment with the KROSS tool in health care services was experienced as acceptable and feasible. The new routine led to increased attention towards poststroke VIs and increased collaboration with vision experts. Tailoring the routine to each practice and how they organise their work can support the integration of a vision assessment in their routines. To promote better vision care poststroke vision assessment and follow up should be included in the stroke care pathways.}, } @article {pmid35294164, year = {2022}, author = {Hasegawa, Y and Motoyama, M and Hamamoto, A and Kimura, S and Kamatari, YO and Kamishina, H and Oh-Hashi, K and Furuta, K and Hirata, Y}, title = {Identification of Novel Oxindole Compounds That Suppress ER Stress-Induced Cell Death as Chemical Chaperones.}, journal = {ACS chemical neuroscience}, volume = {13}, number = {7}, pages = {1055-1064}, doi = {10.1021/acschemneuro.2c00064}, pmid = {35294164}, issn = {1948-7193}, mesh = {Cell Death ; *Endoplasmic Reticulum Stress ; *Hippocampus/metabolism ; Oxindoles/pharmacology ; }, abstract = {Endoplasmic reticulum (ER) stress and oxidative stress lead to protein misfolding, and the resulting accumulation of protein aggregates is often associated with the pathogenesis of neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and prion disease. Small molecules preventing these pathogenic processes may be effective interventions for such neurodegenerative disorders. In this paper, we identify several novel oxindole compounds that can prevent ER stress- and oxidative stress-induced cell death. Among them, derivatives of the lead compound GIF-0726-r in which a hydrogen atom at the oxindole ring 5 position is substituted with a methyl (GIF-0852-r), bromine (GIF-0854-r), or nitro (GIF-0856-r) group potently suppressed global ER stress. Furthermore, GIF-0854-r and -0856-r prevented protein aggregate accumulation in vitro and in cultured hippocampal HT22 neuronal cells, indicating that these two compounds function effectively as chemical chaperones. In addition, GIF-0852-r, -0854-r, and -0856-r prevented glutamate-induced oxytosis and erastin-induced ferroptosis. Collectively, these results suggest that the novel oxindole compounds GIF-0854-r and -0856-r may be useful therapeutics against protein-misfolding diseases as well as valuable research tools for studying the molecular mechanisms of ER and oxidative stress.}, } @article {pmid35284290, year = {2022}, author = {Zhou, J and Yan, F and Xu, J and Lu, Q and Zhu, X and Gao, B and Zhang, H and Yang, R and Luo, Y}, title = {Diagnosis of steatohepatitis and fibrosis in biopsy-proven nonalcoholic fatty liver diseases: including two-dimension real-time shear wave elastography and noninvasive fibrotic biomarker scores.}, journal = {Quantitative imaging in medicine and surgery}, volume = {12}, number = {3}, pages = {1800-1814}, pmid = {35284290}, issn = {2223-4292}, abstract = {BACKGROUND: The aim of this retrospective study was to evaluate the accuracy of two-dimension real-time shear wave elastography (2D-SWE) for the diagnosis of steatohepatitis and fibrosis in a cohort patients confirmed nonalcoholic fatty liver diseases (NAFLD) by liver biopsy, and compare with four noninvasive fibrotic biomarker scores (NFS, FIB-4, BARD and APRI).

METHODS: 116 NAFLD patients and 23 normal control group were enrolled. The diagnostic performance of 2D-SWE and four noninvasive fibrotic biomarker scores was evaluated based on histopathological inflammation grades and fibrosis stages (F) according to Kleiner/Brunt et al.'s criteria classification. 5-fold cross validation and receiver operating characteristics curve (ROC) analyses were used to obtain an assessment of 2D-SWE and four noninvasive fibrotic biomarker scores; then cross validated area under the curves (AUCs) were compared using the test of Delong. Meanwhile, influence of steatosis on liver stiffness measurement (LSM) of 2D-SWE was also studied.

RESULTS: Liver stiffness measured by 2D-SWE proved to be an excellent diagnostic indicator for detecting steatohepatitis (AUROC =0.88), and fibrosis: ≥F2 stage (AUROC =0.86), ≥F3 stage (AUROC =0.89) and =F4 stage (AUROC =0.90) with the cutoff values were 7.3, 10.0, 11.6 and 12.6 kPa, respectively. Compared with fibrotic scores, 2D-SWE had the highest AUROC for predicting ≥F2, ≥F3, =F4 by Delong test (all P<0.05). No statistic differences of LSM were found among different steatosis levels (P=0.97).

CONCLUSIONS: The stiffness measured by 2D-SWE could be used to noninvasively identify steatohepatitis and stage fibrosis in NAFLD patients. Moreover, the diagnosis efficiency of the stiffness measured by 2D-SWE could not be influenced by steatosis.}, } @article {pmid35282604, year = {2022}, author = {Nakao, S and Nishida, T and Sonoda, KH}, title = {Removal of MIRAgel scleral buckle implants using Yankauer suction catheter with adjusted diameter.}, journal = {American journal of ophthalmology case reports}, volume = {26}, number = {}, pages = {101470}, pmid = {35282604}, issn = {2451-9936}, abstract = {PURPOSE: A variety of removal methods have been reported for cases wherein MIRAgel-associated complications have occurred. Recently, Santorum et al. reported an aspiration method using a metal microcannula. Herein, we report a novel alternative approach using Yankauer suction catheter based on Santorum et al.'s method.

OBSERVATIONS: This retrospective case involved a 40-year-old Caucasian man with MIRAgel implant-associated swelling-related complications (strabismus and disfiguring mass effect), who underwent suction-assisted implant removal in January 2020 at Kyushu University Hospital. Surgery was conducted under general anesthesia with an incision made in the superior quadrant, and the degraded MIRAgel implant was aspirated using a Yankauer suction catheter instrument with its diameter adjusted to the space. At the one-month follow-up, there were no early postsurgical complications, and the retina remained completely attached.

CONCLUSIONS: Yankauer suction catheter is a useful instrument for removal of MIRAgel scleral buckle implants. It is made up of polyvinyl chloride, which is safer and cheaper, and can be cut to adjust the instrument's diameter according to the surgical field.}, } @article {pmid35281153, year = {2021}, author = {Shivakumar, B and Arunakshi, and Niveditha, and Shivaprasad, and Manjuprasad, }, title = {Validation of demirjian's 8-teeth method of age estimation in the population of Bengaluru.}, journal = {Journal of oral and maxillofacial pathology : JOMFP}, volume = {25}, number = {3}, pages = {499-502}, pmid = {35281153}, issn = {0973-029X}, abstract = {INTRODUCTION: Demirjian's method of dental age assessment estimates the overall dental age by scoring based on the stage of tooth formation, using panoramic radiographs. This method was primarily based on data acquired from individuals of French-Canadian origin. It has since been applied and modified for the Indian population. Therefore, the aim of the present study is to assess the reliability of the Indian formula in the population of Bengaluru.

MATERIALS AND METHODS: Dental maturity of 297 subjects between 9 and 17 years was assessed using the India-specific formula of Demirjian et al.'s 8-teeth method and the chronological age of each subject was calculated. Pearson's correlation, Independent student test/Mann-Whitney test and Chi-square test were used for statistical analysis of the results obtained.

RESULTS AND DISCUSSION: A very strong correlation (P < 0.001) between the chronological and estimated age by Demirjian's method was obtained. The mean absolute error among the total samples was not significant and majority of the error in the estimated age was <1 year in males and females, indicating that the India specific formula gave nearly accurate estimation of the chronological age of the sample subjects.

CONCLUSION: Demirjian's Indian formula is relaible in the population of Bengaluru.}, } @article {pmid35274226, year = {2022}, author = {Fleming, WH}, title = {Complex Moral Injury: Shattered Moral Assumptions.}, journal = {Journal of religion and health}, volume = {61}, number = {2}, pages = {1022-1050}, pmid = {35274226}, issn = {1573-6571}, mesh = {Clergy ; Humans ; *Military Personnel ; Morals ; *Stress Disorders, Post-Traumatic/therapy ; United States ; *Veterans ; }, abstract = {An infographic model of moral injury (MI) is introduced in this conceptual paper that distinguishes the development of a worldview discrepancy-induced genus of MI, called complex moral injury (C-MI), from a standard expression of moral injury (S-MI), clearly delineated as perpetration-focused and a violation of moral belief in the contemporary view. It builds upon a previous essay that examined the potential of paradoxical circumstance (e.g., clashes of value, competing moral expectations, and moral paradox) to inflict MI among military personnel during wartime (Fleming in J Relig Health 60(5):3012-3033, 2021). Accordingly, it heeds Litz et al.'s recommendation to expand the research of MI beyond the effects of perpetration and investigate the impact of morally injurious events that shake one's core moral beliefs about the world and self (Litz et al. in Clin Psychol Rev 29(8):695-706, 2009). A review of definitional, scale, and qualitative studies shows evidence of a nuanced and complex form of MI that presents as moral disorientation and is a response to a disruption and subsequent failure of foundational moral beliefs to adequately appraise ethical problems and inform moral identity. Interrelations between MI, assumptive world, and meaning theories suggest the mechanism of C-MI and potential therapies. Case studies from a Veterans Administration hospital in the United States and a walk through the diagram will help illustrate the model. Clinical implications of a definition that includes morally injurious events that shatter fundamental moral assumptions are discussed. The role of chaplains in facilitating acceptance and meaning-making processes is recommended for C-MI recovery. Acknowledging the model's need for empirical support, a plausible scale is discussed for future research.}, } @article {pmid35272515, year = {2022}, author = {Yoong, SQ and Goh, HS and Zhang, H}, title = {Death doulas as supportive companions in end-of-life care: A scoping review.}, journal = {Palliative medicine}, volume = {36}, number = {5}, pages = {795-809}, doi = {10.1177/02692163221080659}, pmid = {35272515}, issn = {1477-030X}, mesh = {*Doulas ; Friends ; Health Personnel/psychology ; *Hospice Care ; Humans ; *Terminal Care ; }, abstract = {BACKGROUND: Death doulas have gained greater attention recently by offering psychosocial, spiritual and other non-clinical support for patients with time-limiting diseases, including their families, with the potential to complement existing end-of-life care services. However, their roles, scope of practice and care impact remain poorly understood.

AIM: To describe existing knowledge on death doulas regarding their roles, care impact, training and regulation.

DESIGN: This scoping review utilised Levac et al.'s framework and textual narrative synthesis to summarise the findings.

DATA SOURCES: PubMed, Scopus, CINAHL, PsycINFO, ProQuest, Google Scholar were searched for relevant articles from inception to 20 May 2021. Empirical studies, narrative reports, unpublished theses and studies in English were included.

RESULTS: Thirteen articles were included. Death doulas take on diverse roles in end-of-life care. Their roles include providing psychosocial, spiritual, practical support, companionship and resource navigation. The positive impacts of engaging a death doula include continuous presence, holistic service and flexible payment regime. The negative aspects include role inconsistencies and confusion among healthcare professionals and the public.

CONCLUSIONS: Death doulas can augment existing end-of-life care services by providing holistic and personalised care services at home or hospital settings. Their roles are still evolving and remain mostly unregulated, with little evidence about their impact. There is a need for more rigorous studies to explore healthcare professionals' views about this role and examine the clinical outcomes among dying persons and their families.}, } @article {pmid35263555, year = {2022}, author = {Keates, N}, title = {A Letter to the Editor Regarding Bambara et al. (2021), "Using Peer Supports to Encourage Adolescents With Autism Spectrum Disorder to Show Interest in Their Conversation Partners".}, journal = {Journal of speech, language, and hearing research : JSLHR}, volume = {65}, number = {4}, pages = {1600-1603}, doi = {10.1044/2022_JSLHR-22-00028}, pmid = {35263555}, issn = {1558-9102}, mesh = {Adolescent ; *Autism Spectrum Disorder/therapy ; *Autistic Disorder ; Communication ; Humans ; Peer Group ; }, abstract = {PURPOSE: The purpose of this letter is to address interpretations regarding Bambara et al.'s (2021) study and help resolve potential for further missteps within this line of research.

CONCLUSION: There is clear value in teaching skills that are wanted by autistic people. The primary issue within the article is that it does not acknowledge the double empathy problem and is constructed based on only a neurotypical system of interpretation or communication style. What is being promoted is to address skills autistic participants request.}, } @article {pmid35262960, year = {2022}, author = {Rudland, JR and Rennie, SC}, title = {Failure to fail: Fear of retribution or a response to neglecting the learner?.}, journal = {Medical education}, volume = {56}, number = {6}, pages = {594-596}, pmid = {35262960}, issn = {1365-2923}, mesh = {*Education, Medical ; *Fear ; Humans ; }, abstract = {Rudland and Rennie comment on Swails et al.'s observation that staff are failing fewer learners, offering reflection on the impact neglecting a learner may have on educator decisions if the failure to fail phenomenon is considered.}, } @article {pmid35262921, year = {2022}, author = {Caton, NR and Hannan, J and Dixson, BJW}, title = {Facial width-to-height ratio predicts fighting success: A direct replication and extension of Zilioli et al. (2014).}, journal = {Aggressive behavior}, volume = {48}, number = {5}, pages = {449-465}, pmid = {35262921}, issn = {1098-2337}, mesh = {Body Mass Index ; *Face/anatomy & histology ; Humans ; Male ; }, abstract = {Zilioli et al. (2014) were the first to show an association between male facial width-to-height ratio (fWHR) and physical aggression and fighting ability in professional mixed-martial-arts fighters. Here, we re-examined this relationship by replicating (using all original measures) and extending (using 23 new variables related to fighting performance) Zilioli et al. (2014) in a statistically well-powered sample of 520 fighters using automatic and manual measures of the fWHR involving both eyelid and eyebrow landmarks, used interchangeably in previous reports (Studies 1-2). Most importantly, we successfully replicated Zilioli et al.'s (2014) central finding that fighters' fWHR, when manually calculated using the eyebrow landmark, predicted their fighting success (p = .004, controlling for body mass index and total fights). Consistent with past criticisms of using fight rather than fighter data to examine fighting success, which have argued that individual fights can be suddenly and unexpectedly determined and do not capture an individual's overall ability to succeed, Study 3 (N = 1367 fights) found no association between fWHR and singular victories. Studies 1-3 showed continual evidence that larger fWHRs were associated with grappling abilities, even after controlling for demographic and allometric factors. Strikingly, Study 3 discovered associations between all fWHR measures and grappling skill that remained robust before and after controlling for 17 different control variables. We discuss that grappling, or the act of taking down an opponent, involves a more aggressive, close-combat approach than does striking. Combined, these results offer additional support for the argument that fWHR may have been shaped by sexual selection.}, } @article {pmid35252382, year = {2022}, author = {Cheng, Z and Cai, K and Xu, C and Zhan, Q and Xu, X and Xu, D and Zeng, Q}, title = {Prognostic Value of Serum Galectin-3 in Chronic Heart Failure: A Meta-Analysis.}, journal = {Frontiers in cardiovascular medicine}, volume = {9}, number = {}, pages = {783707}, pmid = {35252382}, issn = {2297-055X}, abstract = {OBJECTIVE: To evaluate the association between serum galectin-3 and all-cause death (ACD) and cardiovascular death (CVD) in patients with chronic heart failure (CHF).

METHODS: The PubMed and Embase databases and Clinical Trials Registry (www.clinicaltrials.gov) were searched for studies with data on serum galectin-3 and ACD and CVD in CHF patients. The hazard ratios (HRs) of ACD and CVD were calculated and presented with 95% CIs. HRs were pooled using fixed effects or random effects models when appropriate. Sensitivity analysis, meta-regression and subgroup analysis were applied to find the origin of heterogeneity. Visual inspection of Begg's funnel plot and Egger's test were performed to assess the possibility publication bias.

RESULTS: Pooled data included the results from 6,440 patients from 12 studies in the meta-analysis. Higher serum galectin-3 was associated with a higher risk of ACD (HR, 1.38; 95% CI, 1.14-1.67) and CVD (HR, 1.13; 95% CI, 1.02-1.25) in CHF patients. In the subgroup analyses, higher serum galectin-3 was associated with an increased risk of ACD in all subgroups. The pooled HR of the shorter follow-up group (1.78; 95% CI, 1.50-2.11) was significantly higher than the pooled HR of the longer follow-up group (1.15; 95% CI, 1.05-1.25). Sensitivity analysis of eliminating one study in each turn indicated that Koukoui et al.'s study had the largest influence on the risk of all-cause death. All-cause death publication bias was not detected (Pr>|z| = 0.35 for Begg's test and P>|t| = 0.15 for Egger's test).

CONCLUSIONS: Serum galectin-3 has prognostic value of both all-cause death and cardiovascular death in CHF. Serum galectin-3 could be useful for risk classification in patients with CHF.

https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=193399.}, } @article {pmid35232453, year = {2022}, author = {Moffett, J and Armitage-Chan, E and Hammond, J and Kelly, S and Pawlikowska, T}, title = {"It's okay to not know …" a qualitative exploration of faculty approaches to working with uncertainty.}, journal = {BMC medical education}, volume = {22}, number = {1}, pages = {135}, pmid = {35232453}, issn = {1472-6920}, mesh = {Faculty ; Health Occupations ; Humans ; Learning ; Qualitative Research ; *Students, Health Occupations ; Uncertainty ; }, abstract = {BACKGROUND: Whilst it is recognised that a capacity to manage uncertainty is an essential aspect of working as a healthcare professional, there is little clear guidance on how to facilitate student learning in this domain. A lack of faculty development opportunities also suggests that health professions' educators may feel ill-equipped to assist students in developing effective approaches to uncertainty. The purpose of this study was to explore a faculty development intervention designed to help educators unpack students' experiences of uncertainty, and identify attributes which may help students to manage uncertain situations.

METHODS: This qualitative study was informed by a constructivist methodological approach, where participants were encouraged to share meaning around the nature of uncertainty in health professions' education. Two 90-min faculty development sessions were held. These sessions invited participants to apply Han et al.'s taxonomy of uncertainty to role-played scenarios of student uncertainty within a focus group setting. Focus group data were collected, and examined using a two-stage, hybrid approach of deductive and inductive thematic analysis.

RESULTS: Han et al.'s taxonomy helped participants to identify multiple sources and issues of uncertainty in the role played scenarios, thus unveiling the extent of uncertainties encountered by health professions' learners. Data analysis revealed four themes overall: "Sources of uncertainty", "Issues of uncertainty", "Uncertainty attributes", and "Learning environment." Participants also contributed to a list of attributes which they considered helpful to undergraduate health professions' students in managing uncertain situations. These included an awareness of the nature of uncertainty within healthcare practice, an ability to recognise uncertainty, and adopting attitudes of adaptability, positivity, and resilience.

CONCLUSIONS: This study highlights the successful use of Han et al.'s taxonomy of uncertainty within a faculty development setting. Our findings suggest that the taxonomy is a practical and versatile tool that health professions' educators can use in shared reflections and conversations around uncertainty with students or colleagues.}, } @article {pmid35227330, year = {2022}, author = {Brierley-Jones, L and Ramsey, L and Canvin, K and Kendal, S and Baker, J}, title = {To what extent are patients involved in researching safety in acute mental healthcare?.}, journal = {Research involvement and engagement}, volume = {8}, number = {1}, pages = {8}, pmid = {35227330}, issn = {2056-7529}, support = {NIHR128070//Health Services and Delivery Research Programme/ ; }, abstract = {BACKGROUND: There is a growing need to involve patients in the development of patient safety interventions. Mental health services, despite their strong history of patient involvement, have been slow to develop patient safety interventions, particularly in inpatient settings.

METHODS: A systematic search was undertaken of both academic and grey literature. Whilst no lay member of the team worked directly on the review, they were part of the project steering group which provided oversight throughout the review process. This included people with lived experience of mental health services. From a research perspective the main focus for lay members was in co-producing the digital technology, the key project output. Smits et al.'s (Res Involv Engagem 6:1-30, 2020) Involvement Matrix was used to taxonomise levels of patient involvement. Studies were included if they were set in any inpatient mental health care context regardless of design. The quality of all selected studies was appraised using Mixed Methods Appraisal Methodology (MMAT).

RESULTS: Fifty-two studies were classified, synthesised and their levels of patient involvement in the research and development of patient safety interventions were taxonomised. Almost two-thirds of studies (n = 33) researched reducing restrictive practices. Only four studies reported engaging patients in the research process as decision-makers, with the remaining studies divided almost equally between engaging patients in the research process as partners, advisors and co-thinkers. Just under half of all studies engaged patients in just one stage of the research process.

CONCLUSION: Involvement of patients in researching patient safety and developing interventions in an inpatient mental health context seems diverse in its nature. Researchers need to both more fully consider and better describe their approaches to involving patients in safety research in inpatient mental health. Doing so will likely lead to the development of higher quality safety interventions.}, } @article {pmid35225216, year = {2022}, author = {Belman, S and Chaguza, C and Kumar, N and Lo, S and Bentley, SD}, title = {A new perspective on ancient Mitis group streptococcal genetics.}, journal = {Microbial genomics}, volume = {8}, number = {2}, pages = {}, pmid = {35225216}, issn = {2057-5858}, support = {/WT_/Wellcome Trust/United Kingdom ; WT QQ2016-2021/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Humans ; Pneumococcal Vaccines ; *Streptococcus/genetics ; Streptococcus mitis/genetics ; *Streptococcus pneumoniae/genetics ; Virulence Factors/genetics ; }, abstract = {Mitis group Streptococcus are human obligate bacteria residing in the nasopharynx and oral cavity. They comprise both commensal and pathogenic species with the most well-known being Streptococcus pneumoniae - a leading cause of meningitis and pneumonia. A primary difference between the commensal and pathogenic species is the presence of the polysaccharide capsule - a major virulence factor in S. pneumoniae, also present in other commensal species. Our current understanding of the evolutionary divergence of the pathogenic and commensal species has been inferred from extant strains. Ancient genomes can further elucidate streptococcal evolutionary history. We extracted streptococcal genome reads from a 5700-year-old ancient metagenome and worked towards characterizing them. Due to excessive within- and between-species recombination common among streptococci we were unable to parse individual species. Further, the composite reads of the ancient metagenome do not fit within the diversity of any specific extant species. Using a capsular gene database and AT-content analysis we determined that this ancient metagenome is missing polysaccharide synthesis genes integral to streptococcal capsule formation. The presence of multiple zinc metalloproteases suggests that adaptation to host IgA1 had begun and the presence of other virulence factors further implies development of close host-microbe interactions, though the absence of a capsule suggests an inability to cause invasive disease. The presence of specific virulence factors such as pneumolysin implies stable maintenance of such genes through streptococcal evolution that may strengthen their value as anti-pneumococcal vaccine antigens, while maintaining awareness of their potential presence in commensal species. Following from Jensen et al.'s initial analysis we provide historical context for this long time human nasopharyngeal resident, the Mitis group Streptococcus.}, } @article {pmid35223059, year = {2022}, author = {Lewis, M and Mathur, MB and VanderWeele, TJ and Frank, MC}, title = {The puzzling relationship between multi-laboratory replications and meta-analyses of the published literature.}, journal = {Royal Society open science}, volume = {9}, number = {2}, pages = {211499}, pmid = {35223059}, issn = {2054-5703}, support = {R01 LM013866/LM/NLM NIH HHS/United States ; R01 CA222147/CA/NCI NIH HHS/United States ; P30 DK116074/DK/NIDDK NIH HHS/United States ; P30 CA124435/CA/NCI NIH HHS/United States ; UL1 TR003142/TR/NCATS NIH HHS/United States ; }, abstract = {What is the best way to estimate the size of important effects? Should we aggregate across disparate findings using statistical meta-analysis, or instead run large, multi-laboratory replications (MLR)? A recent paper by Kvarven, Strømland and Johannesson (Kvarven et al. 2020 Nat. Hum. Behav. 4, 423-434. (doi:10.1038/s41562-019-0787-z)) compared effect size estimates derived from these two different methods for 15 different psychological phenomena. The authors reported that, for the same phenomenon, the meta-analytic estimate tended to be about three times larger than the MLR estimate. These results are a specific example of a broader question: What is the relationship between meta-analysis and MLR estimates? Kvarven et al. suggested that their results undermine the value of meta-analysis. By contrast, we argue that both meta-analysis and MLR are informative, and that the discrepancy between the two estimates that they observed is in fact still largely unexplained. Informed by re-analyses of Kvarven et al.'s data and by other empirical evidence, we discuss possible sources of this discrepancy and argue that understanding the relationship between estimates obtained from these two methods is an important puzzle for future meta-scientific research.}, } @article {pmid35220903, year = {2022}, author = {Morais, R and Bernardes, S and Verdonk, P}, title = {What is gender awareness in health? A scoping review of the concept, its operationalization, and its relation to health outcomes.}, journal = {Women & health}, volume = {62}, number = {3}, pages = {181-204}, doi = {10.1080/03630242.2022.2041150}, pmid = {35220903}, issn = {1541-0331}, mesh = {Delivery of Health Care ; Female ; *Health Personnel ; Humans ; Male ; Outcome Assessment, Health Care ; *Sexism ; }, abstract = {Gender awareness emerged in the 1990s and aimed to provide awareness and sympathy toward the needs of women, measuring health-care providers' attitudes toward them and understand if providers possessed the knowledge for appropriate care. According to Miller et al.'s seminal model, gender awareness incorporates three sub-dimensions: gender sensitivity, gender ideology, and knowledge. Gender awareness has the potential to minimize gender bias in health care, improving the ecological validity of research. This scoping review provides an analysis of how gender awareness has been conceptualized, operationalized, and investigated in its relationship with health-related outcomes. A search was conducted on PubMed, PsycINFO, and ERIC. The relevance of 2.589 articles was assessed and 14 empirical studies were selected and included. Difficulties conceptualizing gender awareness were found and gender awareness and gender sensitivity were often presented as interchangeable. Most papers aimed to measure and compare levels of gender awareness among health professionals and the relationship between gender awareness and relevant health-related outcomes was not studied. Drawing upon a critical analysis of our findings, a proposal for a revised gender awareness conceptualization and operationalization is put forth as to inform novel research on its association with gender bias in health and health care.}, } @article {pmid35203929, year = {2022}, author = {Kelly, RE and Ahmed, AO and Hoptman, MJ}, title = {What Do These Findings Tell Us? Comment on Tinella et al. Cognitive Efficiency and Fitness-to-Drive along the Lifespan: The Mediation Effect of Visuospatial Transformations. Brain Sci. 2021, 11, 1028.}, journal = {Brain sciences}, volume = {12}, number = {2}, pages = {}, pmid = {35203929}, issn = {2076-3425}, abstract = {Tinella et al.'s recent article [...].}, } @article {pmid35200138, year = {2022}, author = {Huiting, W and Dekker, SL and van der Lienden, JCJ and Mergener, R and Musskopf, MK and Furtado, GV and Gerrits, E and Coit, D and Oghbaie, M and Di Stefano, LH and Schepers, H and van Waarde-Verhagen, MAWH and Couzijn, S and Barazzuol, L and LaCava, J and Kampinga, HH and Bergink, S}, title = {Targeting DNA topoisomerases or checkpoint kinases results in an overload of chaperone systems, triggering aggregation of a metastable subproteome.}, journal = {eLife}, volume = {11}, number = {}, pages = {}, pmid = {35200138}, issn = {2050-084X}, support = {R01 GM126170/GM/NIGMS NIH HHS/United States ; }, mesh = {Ataxia Telangiectasia Mutated Proteins/*metabolism ; DNA Damage ; DNA Topoisomerases/*metabolism ; HEK293 Cells ; HSP70 Heat-Shock Proteins/metabolism ; Humans ; Molecular Chaperones/*metabolism ; Peptides/metabolism ; Protein Aggregates ; Protein Folding ; Proteome/metabolism ; alpha-Crystallin B Chain/metabolism ; }, abstract = {A loss of the checkpoint kinase ataxia telangiectasia mutated (ATM) leads to impairments in the DNA damage response, and in humans causes cerebellar neurodegeneration, and an increased risk of cancer. A loss of ATM is also associated with increased protein aggregation. The relevance and characteristics of this aggregation are still incompletely understood. Moreover, it is unclear to what extent other genotoxic conditions can trigger protein aggregation as well. Here, we show that targeting ATM, but also ATR or DNA topoisomerases, results in the widespread aggregation of a metastable, disease-associated subfraction of the proteome. Aggregation-prone model substrates, including Huntingtin exon 1 containing an expanded polyglutamine repeat, aggregate faster under these conditions. This increased aggregation results from an overload of chaperone systems, which lowers the cell-intrinsic threshold for proteins to aggregate. In line with this, we find that inhibition of the HSP70 chaperone system further exacerbates the increased protein aggregation. Moreover, we identify the molecular chaperone HSPB5 as a cell-specific suppressor of it. Our findings reveal that various genotoxic conditions trigger widespread protein aggregation in a manner that is highly reminiscent of the aggregation occurring in situations of proteotoxic stress and in proteinopathies.}, } @article {pmid35189029, year = {2022}, author = {Auer, A and Settypalli, TBK and Mouille, B and Angot, A and De Battisti, C and Lamien, CE and Cattoli, G}, title = {Comparison of the sensitivity, specificity, correlation and inter-assay agreement of eight diagnostic in vitro assays for the detection of African swine fever virus.}, journal = {Transboundary and emerging diseases}, volume = {69}, number = {5}, pages = {e3231-e3238}, doi = {10.1111/tbed.14491}, pmid = {35189029}, issn = {1865-1682}, support = {//The Veterinary Diagnostic Laboratory (VETLAB) Network is a global network of national veterinary laboratories coordinated by the Animal Production and Health Section (APH) of the Joint FAO/IAEA Centre of Nuclear Techniques in Food and Agriculture/ ; }, mesh = {*African Swine Fever/diagnosis/epidemiology ; *African Swine Fever Virus/genetics ; Animals ; DNA, Viral/genetics ; Real-Time Polymerase Chain Reaction/methods/veterinary ; Sensitivity and Specificity ; Swine ; *Swine Diseases ; }, abstract = {With the recent spread of African swine fever (ASF) in Europe, Asia and the Caribbean region, after being endemic for decades in Africa, PCR-based commercial kits and various master mixes are increasingly being used in addition to the Office International des Epizooties-recommended protocol from King et al. (World Organization for Animal Health). Often, the availability and cost of commercial kits or master mixes can be a limiting factor for diagnostic laboratories, in addition to the requirements for transportation and storage of temperature-sensitive reagents in remote areas. In such cases, alternatives should be ready to maximize surveillance and mining of ASF. To evaluate alternatives, we tested five commercial quantitative real-time PCR (qPCR) master mixes from Applied Biosystems, Bio-Rad, Biotechrabbit, Promega and Qiagen using the same primers and probe mix derived from the King et al.'s protocol for the sensitivity, specificity, correlation and inter-assay agreement. We further included three ad hoc molecular diagnostic kits (VetMax™ African Swine Fever Virus Detection Kit [Applied Biosystems], ID Gene African Swine Fever Duplex [ID-Vet] and Virotype ASF PCR Kit [Qiagen/Indical]). The limit of detection (LOD) was assessed for each assay. The comparative study panel comprised 83 archived DNA samples from ASF virus (ASFV) clinical samples, belonging to five different genotypes from outbreaks in 16 countries in Asia and Africa. The analytical specificity was assessed against a panel of swine pathogens. The LOD ranged from 13 to 41 gene copies per reaction; VetMax ™ African Swine Fever Virus Detection Kit from Applied Biosystems exhibited the lowest detection limit (13 gene copies per reaction) and iQ Supermix from Bio-Rad the highest detection limit (41 gene copies per reaction). Cq values obtained from the lowest dilution, in which all replicates (n = 25) could still be amplified (50 gene copies per reaction), were not significantly different between kits using Kruskal-Wallis test. Inter-assay agreement was assessed using statistical test Fleiss-Kappa and was shown to be excellent in all cases. Agreement using statistical test Bland-Altman was good for samples with Cq values <25 and moderate for Cq values >25. We conclude that all the assays evaluated in this study can be used for the routine detection of ASFV.}, } @article {pmid35187490, year = {2022}, author = {Olesen, LK and la Cour, K and With, H and Handberg, C}, title = {Reflections of family caregivers and health professionals on the everyday challenges of caring for persons with amyotrophic lateral sclerosis and cognitive impairments: a qualitative study.}, journal = {Palliative care and social practice}, volume = {16}, number = {}, pages = {26323524221077702}, pmid = {35187490}, issn = {2632-3524}, abstract = {AIMS AND OBJECTIVES: To explore reflections of family caregivers and health professionals regarding the challenges involved in caring for persons with amyotrophic lateral sclerosis and cognitive and/or behavioral impairments (PALS/CIs).

BACKGROUND: Family caregivers of PALS/CIs are highly burdened and at great risk of psychological sequela. Professionals working with these families can be negatively affected on their well-being and are at risk of burnout.

DESIGN: The design was a qualitative interview study.

METHODS: One focus group and 10 individual semi-structured interviews were conducted with seven family caregivers and nine professionals after the death of a PALS/CIs. The analysis was guided by the interpretive description methodology and the theory of sense of coherence. This study adheres to the COREQ guidelines and the ICMJE recommendations.

RESULTS: The family caregivers' challenges regarding coping with everyday needs related to the sick person were associated with 'Accepting that nothing else matters', 'Adjusting to new roles while balancing', and 'Realizing different values in relationships'; whereas the professionals' challenges were related to 'Collaboration a balancing act', 'Working in a home of sorrow', and 'Coordinating threads to tie'.

CONCLUSION: Family caregivers found coping with the complexity of the diseases a challenge, and their everyday life needed constant adjustment to new roles, coping with inappropriate behavior, and navigating through the progression of the diseases of their sick relatives while collaborating with numerous professionals. The professionals struggled with coordinating and collaborating with the families and with other colleagues due to the severeness and complexity of diseases.

Findings point to the importance of relationships for caregivers and professionals and a need to provide support through an online palliative rehabilitation program that encompass coping strategies in relation to the diseases.

TRIAL REGISTRATION DETAILS: Id no. NCT04638608.}, } @article {pmid35182305, year = {2023}, author = {Sun, PP}, title = {The Influence of Cognitive, Affective, and Sociocultural Individual Differences on L2 Chinese Speech Performance: A Multiple Indicators Multiple Causes Approach.}, journal = {Journal of psycholinguistic research}, volume = {52}, number = {1}, pages = {217-239}, pmid = {35182305}, issn = {1573-6555}, support = {18YJC740086//Ministry of Education of the People's Republic of China/ ; 19CYY008//National Social Science Foundation of China/ ; }, mesh = {Humans ; Cognition ; Individuality ; Language ; *Multilingualism ; *Speech ; }, abstract = {Informed by Segalowitz's (Cognitive bases of second language fluency, Routledge, 2010) L2 speech production model and MacIntyre et al.'s (Mod Lang J 82(4):545-562, 1998. https://doi.org/10.1111/j.1540-4781.1998.tb05543.x) L2 willingness to communicate model, this study sought to understand the influence of cognitive, affective and sociocultural individual differences on advanced learners' L2 Chinese speech performance. A total of 240 advanced L2 Chinese learners in China participated in the study. The participants' perceptions of the impact of cognitive, affective, and sociocultural factors on their L2 Chinese speech performance were measured by an adapted questionnaire. A speaking test, following the Hanyu Shuiping Kouyu Kaoshi (HSKK, an international standardized L2 Chinese speaking proficiency test for non-native speakers), was employed to evaluate the participants' L2 Chinese speech performance. The results of multiple indicators multiple causes (MIMIC) analysis show that (1) cognitive factors such as cognitive fluency, expression practice strategy, and assistance strategy, (2) affective factors such as speaking self-efficacy, speaking anxiety, and speaking motivation, and (3) sociocultural factors such as attitudes toward target language class and attitudes toward target language culture jointly influence advanced L2 Chinese learners' speech performance. Results and implications of the present study are discussed for enhancing learners' L2 Chinese speech performance.}, } @article {pmid35179485, year = {2022}, author = {Lidborg, LH and Cross, CP and Boothroyd, LG}, title = {A meta-analysis of the association between male dimorphism and fitness outcomes in humans.}, journal = {eLife}, volume = {11}, number = {}, pages = {}, pmid = {35179485}, issn = {2050-084X}, mesh = {*Choice Behavior ; Female ; Humans ; Male ; Masculinity ; *Sex Characteristics ; Sexual Behavior ; Testosterone ; }, abstract = {Humans are sexually dimorphic: men and women differ in body build and composition, craniofacial structure, and voice pitch, likely mediated in part by developmental testosterone. Sexual selection hypotheses posit that, ancestrally, more 'masculine' men may have acquired more mates and/or sired more viable offspring. Thus far, however, evidence for either association is unclear. Here, we meta-analyze the relationships between six masculine traits and mating/reproductive outcomes (96 studies, 474 effects, N = 177,044). Voice pitch, height, and testosterone all predicted mating; however, strength/muscularity was the strongest and only consistent predictor of both mating and reproduction. Facial masculinity and digit ratios did not significantly predict either. There was no clear evidence for any effects of masculinity on offspring viability. Our findings support arguments that strength/muscularity may be sexually selected in humans, but cast doubt regarding selection for other forms of masculinity and highlight the need to increase tests of evolutionary hypotheses outside of industrialized populations.}, } @article {pmid35179057, year = {2023}, author = {Geer, EA and Ganley, C}, title = {Sex differences in social and spatial perspective taking: A replication and extension of Tarampi et al. (2016).}, journal = {Quarterly journal of experimental psychology (2006)}, volume = {76}, number = {1}, pages = {93-108}, doi = {10.1177/17470218221085117}, pmid = {35179057}, issn = {1747-0226}, mesh = {Humans ; Male ; Female ; *Sex Characteristics ; *Space Perception ; Cues ; }, abstract = {Tarampi and colleagues (2016) found that females performed better on spatial perspective-taking tasks when social information was present. They interpreted this finding to suggest that adding social information would uniquely improve the performance of females due to their better social perspective taking. In this replication and extension study, we tested an alternative explanation for their results: the tasks with social information also provided spatial information which could explain improved performance. In a study with 278 college students, we used the two versions of the tasks from their study (no social or spatial information and with social and spatial information) and added two versions that isolate only social and only spatial information. Our replication of Tarampi et al.'s analyses found no difference in females' performance on the tasks; however, when both females and males were included, we found some evidence for better performance in the social and spatial condition. Examining both males' and females' performance in all four conditions, we found that males outperformed females. In addition, participants who completed tasks with spatial information performed better. Findings suggest the difference observed in Tarampi et al. may have been due to the inclusion of spatial information, not social information, that improves task performance for both females and males. These results suggest that spatial perspective-taking performance is better when given even subtle spatial cues, but that social information alone does not appear to improve performance, despite ties with social perspective taking.}, } @article {pmid35172393, year = {2023}, author = {Geambașu, A and Spit, S and van Renswoude, D and Blom, E and Fikkert, PJPM and Hunnius, S and Junge, CCMM and Verhagen, J and Visser, I and Wijnen, F and Levelt, CC}, title = {Robustness of the rule-learning effect in 7-month-old infants: A close, multicenter replication of Marcus et al. (1999).}, journal = {Developmental science}, volume = {26}, number = {1}, pages = {e13244}, pmid = {35172393}, issn = {1467-7687}, mesh = {Infant ; Humans ; *Learning ; *Speech ; }, abstract = {We conducted a close replication of the seminal work by Marcus and colleagues from 1999, which showed that after a brief auditory exposure phase, 7-month-old infants were able to learn and generalize a rule to novel syllables not previously present in the exposure phase. This work became the foundation for the theoretical framework by which we assume that infants are able to learn abstract representations and generalize linguistic rules. While some extensions on the original work have shown evidence of rule learning, the outcomes are mixed, and an exact replication of Marcus et al.'s study has thus far not been reported. A recent meta-analysis by Rabagliati and colleagues brings to light that the rule-learning effect depends on stimulus type (e.g., meaningfulness, speech vs. nonspeech) and is not as robust as often assumed. In light of the theoretical importance of the issue at stake, it is appropriate and necessary to assess the replicability and robustness of Marcus et al.'s findings. Here we have undertaken a replication across four labs with a large sample of 7-month-old infants (N = 96), using the same exposure patterns (ABA and ABB), methodology (Headturn Preference Paradigm), and original stimuli. As in the original study, we tested the hypothesis that infants are able to learn abstract "algebraic" rules and apply them to novel input. Our results did not replicate the original findings: infants showed no difference in looking time between test patterns consistent or inconsistent with the familiarization pattern they were exposed to.}, } @article {pmid35168660, year = {2022}, author = {Brinchmann, BS and Lyngmo, S and Herholdt-Lomholdt, SM and Blix, BH}, title = {Multiple perspectives and dialogue in understanding experiences of living with eating disorders: Two narratives-four unpackings.}, journal = {Journal of eating disorders}, volume = {10}, number = {1}, pages = {24}, pmid = {35168660}, issn = {2050-2974}, abstract = {BACKGROUND: This is a response to Conti et al.'s article, "Listening in the dark: why we need stories of people living with severe and enduring anorexia nervosa" (published in JED, 2016), and its call for relational metaphors and a relational approach to supplement the traditional medical/psychological diagnostic language used to describe the life experiences and complex emotions of people affected by an eating disorder.

METHODS: Four authors with different backgrounds unpack two narratives, 'The Prima Donna with the Green Dress' and 'Breaking down the Wall', both narrated during fieldwork in multifamily therapy. The narratives are unpacked from the perspective of a therapist within multifamily therapy, a researcher who conducted the fieldwork, a researcher based in phenomenology and a researcher based in narrative inquiry. The authors enter into dialogue with the narratives, and with each other.

RESULTS: The four authors focus on different elements within the narratives and understand them differently. One, focuses on strength and pride, and art expression as a different form of language for people living with an eating disorder. Another, on the experience of isolation, boundaries, and balancing openness and closedness. A third, sees the narratives as expressing a wish to see and be seen, and the fourth focuses on the absence of, and longing for, a shared space to explore.

CONCLUSION: The aim is not to reach a correct or shared interpretation of the narratives but to explore how different perspectives may contribute to different insights, not only about one family in particular but about, more generally, the experiences of people living with an eating disorder. Our work shows the significance of engaging with multiple perspectives and dialogue as supplements to the traditional medical/psychiatric diagnostic language in both clinical practice and research.}, } @article {pmid35166185, year = {2023}, author = {Liu, Y and Groot, B and de Kock, L and Abma, T and Dedding, C}, title = {How participatory arts can contribute to Dutch older adults' wellbeing - revisiting a taxonomy of arts interventions for people with dementia.}, journal = {Arts & health}, volume = {15}, number = {2}, pages = {153-168}, pmid = {35166185}, issn = {1753-3023}, mesh = {Humans ; Aged ; *Art ; *Art Therapy ; Emotions ; Family ; *Dementia/therapy ; }, abstract = {BACKGROUND: A growing body of evidence suggests the positive impact of arts on health and wellbeing. The mechanisms underlying the impact however, remain overlooked.

METHODS: 38 Semi-structured interviews were held with 30 older adults and 10 artists, involved in five participatory art projects in the Netherlands. Case-based framework and cross-over analyses were done on the basis of Cousins et al.'s taxonomy.

RESULTS: Participatory art initiatives contributed to the wellbeing of older adults in a complex interplay with the artist, art form, group of participants, material aspects and continuity of activities. A welcoming environment appeared a consistent underlying mechanism for participants to grow on a personal and artistic level, connect with others and feel supported in their psychosocial wellbeing.

CONCLUSION: This article demonstrates the important social function participatory art can have for older adults, and argues for the importance of a thorough consideration of the context wherein underlying mechanisms and outcomes emerge.}, } @article {pmid35158620, year = {2022}, author = {Kis, A and Bolló, H and Gergely, A and Topál, J}, title = {Social Stimulation by the Owner Increases Dogs' (Canis familiaris) Social Susceptibility in a Food Choice Task-The Possible Effect of Endogenous Oxytocin Release.}, journal = {Animals : an open access journal from MDPI}, volume = {12}, number = {3}, pages = {}, pmid = {35158620}, issn = {2076-2615}, support = {K128448//National Research, Development and Innovation Fund (Hungary)/ ; FK128242//National Research, Development and Innovation Fund (Hungary)/ ; bo_665_19//János Bolyai Research Scholarship of the Hungarian Academy of Sciences/ ; }, abstract = {Recent evidence suggests a human-like susceptibility to social influence in dogs. For example, dogs tend to ignore their 'natural' preference for the larger amount of food after having seen a human's explicit preference for a smaller quantity. However, it is still unclear whether this tendency to conform to the partner's behaviour can be influenced by social stimuli and/or the neurohormone oxytocin as primers to prosocial predispositions. In Experiment I, eighty two dogs were tested using Prato-Previde et al.'s food quantity preference task. In Experiment I, we investigated in a 2 × 2 design how (i) a 10-minute-long social stimulation by the owner versus a socially ignoring pre-treatment as well as (ii) on-line ostensive communications versus no communication during task demonstration affect dogs' (N = 82) choices in the abovementioned food choice task. Results indicate that the owners' pre-treatment with social stimuli (eye contact, petting) increased dogs' susceptibility to the experimenter's food preference, but the salient ostensive addressing signals accompanying human demonstration masked this social priming effect. In Experiment II, N = 32 dogs from the subjects of Experiment I were retested after oxytocin (OT) or placebo (PL) pre-treatments. This experiment aimed to study whether intranasal administration of oxytocin as compared to placebo treatment would similarly increase dogs' tendency to re-enact the human demonstrator's counterproductive choice in the same task. Results showed an increased susceptibility to the human preference in the OT group, suggesting that both socially stimulating pre-treatment and the intranasal administration of oxytocin have similar priming effects on dogs' social susceptibility.}, } @article {pmid35156404, year = {2022}, author = {Krause, KL and Koerner, N and Antony, MM}, title = {Cognitive Restructuring Before Versus After Exposure: Effect on Expectancy and Outcome in Individuals With Claustrophobia.}, journal = {Behavior modification}, volume = {46}, number = {6}, pages = {1432-1459}, pmid = {35156404}, issn = {1552-4167}, support = {//CIHR/Canada ; }, mesh = {*Cognitive Behavioral Therapy/methods ; Cognitive Restructuring ; Humans ; *Implosive Therapy ; Learning ; *Phobic Disorders ; }, abstract = {Maximizing the discrepancy between expected and actual outcomes during exposure (i.e., expectancy violation) is thought to optimize inhibitory learning. The current study examined Craske et al.'s suggestion that engaging in cognitive restructuring (CR) before exposure prematurely reduces expectancy and mitigates outcomes. Participants (N = 93) with claustrophobia were randomly assigned to either 15 minutes of CR before exposure (CR Before) or 15 minutes of CR after exposure (CR After). Although the CR Before condition experienced greater expectancy reduction before exposure than the CR After condition, both groups experienced similar overall expectancy reduction by the end of the intervention. Groups experienced similar gains, with large significant improvement at posttreatment and follow-up. Results suggest that both cognitive therapy and exposure therapy lead to expectancy reduction, but that the order of these interventions does not impact outcome. Clinicaltrials.org registration #NCT03628105.}, } @article {pmid35154743, year = {2022}, author = {Holm, CE and Grazal, CF and Raedkjaer, M and Baad-Hansen, T and Nandra, R and Grimer, R and Forsberg, JA and Petersen, MM and Skovlund Soerensen, M}, title = {Development and comparison of 1-year survival models in patients with primary bone sarcomas: External validation of a Bayesian belief network model and creation and external validation of a new gradient boosting machine model.}, journal = {SAGE open medicine}, volume = {10}, number = {}, pages = {20503121221076387}, pmid = {35154743}, issn = {2050-3121}, abstract = {BACKGROUND: Bone sarcomas often present late with advanced stage at diagnosis and an according, varying short-term survival. In 2016, Nandra et al. generated a Bayesian belief network model for 1-year survival in patients with bone sarcomas. The purpose of this study is: (1) to externally validate the prior 1-year Bayesian belief network prediction model for survival in patients with bone sarcomas and (2) to develop a gradient boosting machine model using Nandra et al.'s cohort and evaluate whether the gradient boosting machine model outperforms the Bayesian belief network model when externally validated in an independent Danish population cohort.

MATERIAL AND METHODS: The training cohort comprised 3493 patients newly diagnosed with bone sarcoma from the institutional prospectively maintained database at the Royal Orthopaedic Hospital, Birmingham, UK. The validation cohort comprised 771 patients with newly diagnosed bone sarcoma included from the Danish Sarcoma Registry during January 1, 2000-June 22, 2016. We performed area under receiver operator characteristic curve analysis, Brier score and decision curve analysis to evaluate the predictive performance of the models.

RESULTS: External validation of the Bayesian belief network 1-year prediction model demonstrated an area under receiver operator characteristic curve of 68% (95% confidence interval, 62%-73%). Area under receiver operator characteristic curve of the gradient boosting machine model demonstrated: 75% (95% confidence interval: 70%-80%), overall model performance by the Brier score was 0.09 (95% confidence interval: 0.077-0.11) and decision curve analysis demonstrated a positive net benefit for threshold probabilities above 0.5. External validation of the developed gradient boosting machine model demonstrated an area under receiver operator characteristic curve of 63% (95% confidence interval: 57%-68%), and the Brier score was 0.14 (95% confidence interval: 0.12-0.16).

CONCLUSION: External validation of the 1-year Bayesian belief network survival model yielded a poor outcome based on a Danish population cohort validation. We successfully developed a gradient boosting machine 1-year survival model. The gradient boosting machine did not outperform the Bayesian belief network model based on external validation in a Danish population-based cohort.}, } @article {pmid35152404, year = {2022}, author = {Yen, H and Huang, CH and Huang, IH and Hung, WK and Su, HJ and Yen, H and Tai, CC and Haw, WY and Flohr, C and Yiu, ZZN and Chi, CC}, title = {Systematic review and critical appraisal of psoriasis clinical practice guidelines: a Global Guidelines in Dermatology Mapping Project (GUIDEMAP).}, journal = {The British journal of dermatology}, volume = {187}, number = {2}, pages = {178-187}, doi = {10.1111/bjd.21047}, pmid = {35152404}, issn = {1365-2133}, mesh = {Academies and Institutes ; *Dermatology ; Europe ; Humans ; North America ; Practice Guidelines as Topic ; *Psoriasis/diagnosis/therapy ; }, abstract = {BACKGROUND: Clinical practice guidelines (CPGs) developed with rigorous methods can help optimize clinical care for patients with psoriasis.

OBJECTIVES: To conduct an updated systematic review and comprehensive critical appraisal of global psoriasis CPGs.

METHODS: A search of MEDLINE and Embase for psoriasis CPGs published between 1 January 2015 and 31 March 2021 was performed. Other guideline repositories were also searched for relevant CPGs. Descriptive analysis was conducted to summarize included guidelines. Three critical appraisal tools were used to assess the quality of included CPGs: the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument, Lenzer et al.'s red flags, and the US Institute of Medicine's (IOM) criteria of trustworthiness.

RESULTS: We included 33 psoriasis CPGs, with 25 openly accessible. Most CPGs were from high sociodemographic index countries in North America and Europe. Five CPGs received 'excellent quality' appraisals across all six AGREE II domains. Stakeholder involvement, rigour of development and applicability were the three domains with the lowest appraisal scores for AGREE II. Twenty-two CPGs raised at least one red flag indicative of potential bias. By the IOM's standards, external review of the guideline draft prior to publication and clear updating procedures were most often not addressed by guidelines, and only three CPGs were assessed as having higher overall trustworthiness.

CONCLUSIONS: Most psoriasis guidelines were unable to consistently demonstrate high quality across multiple appraisal tools. The EuroGuiDerm guideline on the systemic treatment of psoriasis vulgaris was the only CPG to receive 'excellent quality' across all six AGREE II domains, to raise no Lenzer's red flags, and to have higher trustworthiness by IOM criteria.}, } @article {pmid35151791, year = {2022}, author = {Mazefsky, CA}, title = {Editorial: The Boundaries of Irritability and Implications for Measurement.}, journal = {Journal of the American Academy of Child and Adolescent Psychiatry}, volume = {61}, number = {5}, pages = {610-611}, pmid = {35151791}, issn = {1527-5418}, support = {R01 HD079512/HD/NICHD NIH HHS/United States ; R01 HD100392/HD/NICHD NIH HHS/United States ; R01 DK100302/DK/NIDDK NIH HHS/United States ; R01 MH110623/MH/NIMH NIH HHS/United States ; }, mesh = {Aggression ; Anger ; Child ; Diagnostic and Statistical Manual of Mental Disorders ; Humans ; Irritable Mood ; }, abstract = {Irritability is a defining feature or symptom in at least 15 DSM-5 disorders,[1] and this does not even account for many more disorders that commonly co-occur with irritability. However, just as the transdiagnostic nature of irritability supports its unequivocal importance in child mental health, it also contributes to criticisms that it is "ubiquitous."[2] How to conceptualize the role of irritability in psychopathology rests on our ability to define it and its boundaries. Unfortunately, there is a lack of consensus on the definition of irritability. In fact, how to disentangle irritability's mood and behavioral components has been described as one of the biggest challenges related to irritability research.[3] This editorial is a commentary on Zik et al.'s[4] study, which takes an emprical approach to determine the overlap between questionnaire measures of irritability, anger, and aggression, thereby informing our conceptualization of irritabiltiy and focusing attention on critical measurement issues such as the impact of informant.}, } @article {pmid35147862, year = {2022}, author = {Xu, L and Naserpour, A and Rezai, A and Namaziandost, E and Azizi, Z}, title = {Exploring EFL Learners' Metaphorical Conceptions of Language Learning: A Multimodal Analysis.}, journal = {Journal of psycholinguistic research}, volume = {51}, number = {2}, pages = {323-339}, pmid = {35147862}, issn = {1573-6555}, mesh = {Female ; Humans ; Iran ; *Language ; Learning ; Male ; Metaphor ; *Multilingualism ; }, abstract = {Owing to the limitations of linguistic modes to portray aptly L2 learners' metaphors of language learning experience, growing attention has been paid to taking advantage of other modes like visual ones to ameliorate this concern. Hence, the present study sought to explore images and metaphors Iranian EFL learners may have in mind about the essence of English language as a foreign learning. To this end, Iranian EFL learners' verbal and non-verbal forms of metaphorical depiction were examined. One intact class, including intermediate male and female learners (n = 11) at a non-profit language institute was selected randomly. The data were collected through both verbal (a single-item questionnaire) and non-verbal (drawings) tools. The learners' drawings and written descriptions were examined so as to both tap into their mental representations of what 'English learning' means to them and get closer insights into the learners' belief system. The study's conceptual framework was mainly built on Oxford et al.'s (System 26:3-50, 1998) perspectives on education and Vygotsky's (Mind in society: the development of higher psychological processes, Harvard University Press, 1978) Socio-cultural theory (SCT) of learning. The multimodal analysis of the metaphors evidenced that the learners' verbal and visual metaphorical representations shared the common perspectives towards English learning. Additionally, the extracted metaphorical concepts disclosed the learners' positive attitudes, enthusiasm, and desire for English learning. Results unveiled that most of the visual and verbal metaphorical depictions portray language learning as a joyful, dynamic and discovery individual process. The study ends with presenting some implications and offering some avenues for further research.}, } @article {pmid35144732, year = {2022}, author = {Burchell, C and Kourmatzis, A and Zhao, Y and Raco, J and Mekonnen, T and Chan, HK and Cheng, S}, title = {Effects of respiratory rate on the fluid mechanics of a reconstructed upper airway.}, journal = {Medical engineering & physics}, volume = {100}, number = {}, pages = {103746}, doi = {10.1016/j.medengphy.2021.103746}, pmid = {35144732}, issn = {1873-4030}, mesh = {Humans ; *Hydrodynamics ; *Models, Biological ; Respiration ; *Respiratory Rate ; *Respiratory System ; Rheology ; }, abstract = {This study aims to utilise particle image velocimetry (PIV) techniques to investigate the time-dependant effects of respiratory rate in the extrathoracic airway, to show how they affect the flow field developed. There has been limited validation of computational fluid dynamics (CFD) models using experimental setups. Furthermore, the large majority of existing CFD models focus on rigid airways, not accounting for active deformation through the breathing cycle. Experiments were carried out to expand upon Zhao et al.'s previous study, in which a single respiratory rate was investigated. This studied utilised a transient, sinusoidal flow profile with two respiratory rates of 10 breaths per minute (BPM) and 25 BPM, both achieving a maximum flow rate correlating to 5 L/min in air to simulate tidal breathing. Results from this study showed that respiratory rate had the greatest influence near the onset of the inspiratory and expiratory manoeuvres, with the higher respiratory rate homogenising later in the cycle. It was shown that airway deformation at the level of the soft palate homogenised flow downstream of the deformation which resulted in a lower peak magnitude velocity for approximately 40% of the cycle at the level of the epiglottis, when compared to the rigid airway model.}, } @article {pmid35143242, year = {2022}, author = {Spicer, SG and Mitchell, CJ and Wills, AJ and Blake, KL and Jones, PM}, title = {Theory protection: Do humans protect existing associative links?.}, journal = {Journal of experimental psychology. Animal learning and cognition}, volume = {48}, number = {1}, pages = {1-16}, doi = {10.1037/xan0000314}, pmid = {35143242}, issn = {2329-8464}, support = {//University of Plymouth/ ; }, mesh = {*Association Learning ; Conditioning, Classical ; *Cues ; Humans ; Inhibition, Psychological ; Learning ; }, abstract = {Theories of associative learning often propose that learning is proportional to prediction error, or the difference between expected events and those that occur. Spicer et al. (2020) suggested an alternative, that humans might instead selectively attribute surprising outcomes to cues that they are not confident about, to maintain cue-outcome associations about which they are more confident. Spicer et al. reported three predictive learning experiments, the results of which were consistent with their proposal ("theory protection") rather than a prediction error account (Rescorla, 2001). The four experiments reported here further test theory protection against a prediction error account. Experiments 3 and 4 also test the proposals of Holmes et al. (2019), who suggested a function mapping learning to performance that can explain Spicer et al.'s results using a prediction-error framework. In contrast to the previous study, these experiments were based on inhibition rather than excitation. Participants were trained with a set of cues (represented by letters), each of which was followed by the presence or absence of an outcome (represented by + or -). Following this, a cue that previously caused the outcome (A+) was placed in compound with another cue (B) with an ambiguous causal status (e.g., a novel cue in Experiment 1). This compound (AB-) did not cause the outcome. Participants always learned more about B in the second training phase, despite A always having the greater prediction error. In Experiments 3 and 4, a cue with no apparent prediction error was learned about more than a cue with a large prediction error. Experiment 4 tested participants' relative confidence about the causal status of cues A and B prior to the AB- stage, producing findings that are consistent with theory protection and inconsistent with the predictions of Rescorla, and Holmes et al. (PsycInfo Database Record (c) 2022 APA, all rights reserved).}, } @article {pmid35143218, year = {2023}, author = {Marsman, M and Waldorp, L and Borsboom, D}, title = {Towards an encompassing theory of network models: Reply to Brusco, Steinley, Hoffman, Davis-Stober, and Wasserman (2019).}, journal = {Psychological methods}, volume = {28}, number = {4}, pages = {757-764}, doi = {10.1037/met0000373}, pmid = {35143218}, issn = {1939-1463}, support = {//Netherlands Organisation for Scientific Research/ ; }, mesh = {Humans ; *Algorithms ; }, abstract = {Network models like the Ising model are increasingly used in psychological research. In a recent article published in this journal, Brusco et al. (2019) provide a critical assessment of the conditions that underlie the Ising model and the eLasso method that is commonly used to estimate it. In this commentary, we show that their main criticisms are unfounded. First, where Brusco et al. (2019) suggest that Ising models have little to do with classical network models such as random graphs, we show that they can be fruitfully connected. Second, if one makes this connection it is immediately evident that Brusco et al.'s (2019) second criticism-that the Ising model requires complete population homogeneity and does not allow for individual differences in network structure-is incorrect. In particular, we establish that if every individual has their own topology, and these individual differences instantiate a random graph model, the Ising model will hold in the population. Hence, population homogeneity is sufficient for the Ising model, but it is not necessary, as Brusco et al. (2019) suggest. Third, we address Brusco et al.'s (2019) criticism regarding the sparsity assumption that is made in common uses of the Ising model. We show that this criticism is misdirected, as it targets a particular estimation algorithm for the Ising model rather than the model itself. We also describe various established and validated approaches for estimating the Ising model for networks that violate the sparsity assumption. Finally, we outline important avenues for future research. (PsycInfo Database Record (c) 2023 APA, all rights reserved).}, } @article {pmid35142607, year = {2022}, author = {Rhodes, K and Barr, KA and Popp, JM and Strober, BJ and Battle, A and Gilad, Y}, title = {Human embryoid bodies as a novel system for genomic studies of functionally diverse cell types.}, journal = {eLife}, volume = {11}, number = {}, pages = {}, pmid = {35142607}, issn = {2050-084X}, support = {F31 HL146171/HL/NHLBI NIH HHS/United States ; R35 GM131726/GM/NIGMS NIH HHS/United States ; R35 GM139580/GM/NIGMS NIH HHS/United States ; }, mesh = {Cell Differentiation/*genetics ; Cell Line ; Embryoid Bodies/*cytology/metabolism ; Female ; *Gene Expression Regulation ; Genome, Human ; Humans ; Induced Pluripotent Stem Cells ; Male ; Sequence Analysis, RNA ; }, abstract = {Practically all studies of gene expression in humans to date have been performed in a relatively small number of adult tissues. Gene regulation is highly dynamic and context-dependent. In order to better understand the connection between gene regulation and complex phenotypes, including disease, we need to be able to study gene expression in more cell types, tissues, and states that are relevant to human phenotypes. In particular, we need to characterize gene expression in early development cell types, as mutations that affect developmental processes may be of particular relevance to complex traits. To address this challenge, we propose to use embryoid bodies (EBs), which are organoids that contain a multitude of cell types in dynamic states. EBs provide a system in which one can study dynamic regulatory processes at an unprecedentedly high resolution. To explore the utility of EBs, we systematically explored cellular and gene expression heterogeneity in EBs from multiple individuals. We characterized the various cell types that arise from EBs, the extent to which they recapitulate gene expression in vivo, and the relative contribution of technical and biological factors to variability in gene expression, cell composition, and differentiation efficiency. Our results highlight the utility of EBs as a new model system for mapping dynamic inter-individual regulatory differences in a large variety of cell types.}, } @article {pmid35135565, year = {2022}, author = {Serhal, E and Pereira, C and Armata, R and Hardy, J and Sockalingam, S and Crawford, A}, title = {Describing implementation outcomes for a virtual community of practice: The ECHO Ontario Mental Health experience.}, journal = {Health research policy and systems}, volume = {20}, number = {1}, pages = {17}, pmid = {35135565}, issn = {1478-4505}, mesh = {*Health Personnel/education ; Humans ; *Mental Health ; Models, Educational ; Ontario ; }, abstract = {BACKGROUND: Project ECHO is a virtual education model aimed at building capacity among healthcare providers to support optimal management for a range of health conditions. The expansion of the ECHO model, further amplified by the pandemic, has demonstrated an increased need to evaluate implementation success to ensure that interventions are implemented as planned. This study describes how Proctor et al.'s implementation outcomes (acceptability, adoption, appropriateness, costs, feasibility, fidelity, penetration, and sustainability) were adapted and used to assess the implementation of ECHO Ontario Mental Health (ECHO-ONMH), a mental health-focused capacity-building programme.

METHODS: Using Proctor et al.'s implementation outcomes, the authors developed an implementation outcomes framework for ECHO-ONMH more generally. Using this, outcome measures and success thresholds were identified for each outcome for the ECHO-ONMH context, and then applied to evaluate the implementation of ECHO-ONMH using data from the first 4 years of the programme.

RESULTS: An ECHO-ONMH implementation outcomes framework was developed using Proctor's implementation outcomes. ECHO-ONMH adapted implementation outcomes suggest that ECHO-ONMH was implemented successfully in all domains except for penetration, which only had participation from 13/14 regions. Acceptability, appropriateness and adoption success thresholds were surpassed for all 4 years, showing strong signs of sustainability. The programme was deemed feasible all 4 years and was found to be more cost-effective. ECHO-ONMH also showed high rates of fidelity to the ECHO model, and high rates of penetration.

CONCLUSIONS: This is the first study to use Proctor et al.'s implementation outcomes to describe implementation success for a virtual capacity-building model. The proposed ECHO implementation outcomes framework provides a base for similar interventions to evaluate implementation success, which is an important precursor to understanding learning, service or health outcomes related to the model. Additionally, these findings can act as a benchmark for other international ECHOs and educational programmes.}, } @article {pmid35129786, year = {2022}, author = {Lima, RA and Drenowatz, C and Pfeiffer, KA}, title = {Expansion of Stodden et al.'s Model.}, journal = {Sports medicine (Auckland, N.Z.)}, volume = {52}, number = {4}, pages = {679-683}, pmid = {35129786}, issn = {1179-2035}, } @article {pmid35129413, year = {2022}, author = {Prochazka, J and Parilakova, K and Rudolf, P and Bruk, V and Jungwirthova, R and Fejtova, S and Masaryk, R and Vaculik, M}, title = {Pain as Social Glue: A Preregistered Direct Replication of Experiment 2 of Bastian et al. (2014).}, journal = {Psychological science}, volume = {33}, number = {3}, pages = {463-473}, doi = {10.1177/09567976211040745}, pmid = {35129413}, issn = {1467-9280}, mesh = {Humans ; *Pain ; Pilot Projects ; *Students ; }, abstract = {Bastian et al. (2014) found that sharing a painful experience promoted later intergroup cooperation. In Bastian et al.'s second experiment, 62 participants were assigned to groups of two to six people each. They performed either two painful or two painless tasks and then played an economic game. The present study consisted of two replications of the experiment: The first was a nonpreregistered pilot study (N = 153 students from the Czech Republic), and the second was a preregistered direct replication (N = 158 students from Slovakia). Important deviations from the original procedure were that (a) gender homogeneity of the small groups was balanced across the conditions and (b) the number of participants in each small group was fixed at three. No relevant effect of shared pain on cooperation emerged. The findings indicate that the true effect of shared pain on cooperation obtained in the original study may have been an overestimate or that the effect is not generally valid across various contexts.}, } @article {pmid35120346, year = {2022}, author = {Tello, HJ and Téllez, DJ and Gonzales, JE}, title = {Identifying Obstetric Mistreatment Experiences in U.S. Birth Narratives: Application of Internationally Informed Mistreatment Typologies.}, journal = {MCN. The American journal of maternal child nursing}, volume = {47}, number = {3}, pages = {138-146}, pmid = {35120346}, issn = {1539-0683}, mesh = {Attitude of Health Personnel ; Delivery, Obstetric ; Female ; Health Personnel ; Humans ; *Maternal Health Services ; Parturition ; Pregnancy ; *Quality of Health Care ; }, abstract = {BACKGROUND: Traumatic births are those resulting in feelings of distress that persist after the birth experience. Health care providers may play a role in these experiences through various forms of mistreatment. Analyses of global birth experiences have generated several domains of mistreatment. This study applies these evidence-based domains of mistreatment as an a priori coding scheme for analysis of 96 oral narratives of U.S.-based births to describe the nature of perceived mistreatment using participants' own descriptions of experiences.

METHOD: Ninety-six transcripts of oral birth stories from 61 participants were coded using the domains of mistreatment experiences described by the Bohren et al.'s (2015) systematic review of obstetric mistreatment.

RESULTS: N = 131 individual experiences of perceived obstetric mistreatment were identified in 41 out of 96 narratives (42.7%). The most frequent types of experiences were Poor Rapport (90 incidences) and Failure to Meet Professional Standards of Care (29).

CLINICAL IMPLICATIONS: Although most women in our study did not perceive any instances of obstetric mistreatment during their childbirth, over 40% of participants noted at least one event that fit one of the typologies we used as a framework for analysis. Visibility and review of the types of perceived mistreatment experiences that occur during birth enables health system leaders to implement prevention and accountability strategies. Most instances of perceived mistreatment during birth may be prevented through intentional implementation of individualized, respectful, supportive care during labor and birth.}, } @article {pmid35114861, year = {2023}, author = {Fosse, A and Svensson, A and Konradsen, I and Abelsen, B}, title = {Tension between local, regional and national levels in Norway's handling of COVID-19.}, journal = {Scandinavian journal of public health}, volume = {51}, number = {7}, pages = {995-1002}, pmid = {35114861}, issn = {1651-1905}, mesh = {Humans ; *COVID-19/epidemiology ; Pandemics ; Focus Groups ; Health Personnel ; Norway/epidemiology ; }, abstract = {AIMS: This study aimed to explore the tension between local, regional, and national authorities evoked by some rural municipalities' decisions to impose local infection-control measures during the first weeks of the COVID-19 pandemic in Norway.

METHODS: Eight municipal Chief Medical Officers of Health (CMOs) participated in semi-structured interviews, and six crisis management teams participated in focus-group interviews. Data were analysed with systematic text condensation. Boin and Bynander's interpretation of crisis management and coordination and Nesheim et al.'s framework for non-hierarchical coordination in the state sector inspired the analysis.

RESULTS: Uncertainty in the face of a pandemic with unknown damage potential, lack of infection-control equipment, patient transport challenges, vulnerable staff situation and planning of local COVID-19 beds were some of the reasons for rural municipalities imposing local infection-control measures the first weeks of the pandemic. Local CMOs' engagement, visibility and knowledge contributed to trust and safety. Differences in perspectives between local, regional and national actors created tension. Existing roles and structures were adjusted, and new informal networks arose.

CONCLUSIONS: Strong municipal responsibility in Norway and the quite unique arrangement with local CMOs in every municipality with the legal right to decide temporary local infection-control measures seemed to facilitate a balance between top-down and bottom-up decision making. Tension between rural, regional and national actors that arose due to local infection-control measures, and the following dialogue and mutual adjustment of perspectives, led to a fruitful balance between national and local measures in Norway's handling of the COVID-19 pandemic.}, } @article {pmid35106672, year = {2022}, author = {Tsenkov, T and Dimitrov, N}, title = {A systematic review of elbow arthroscopy complications : Complications, risk factors, and safety tips.}, journal = {International orthopaedics}, volume = {46}, number = {5}, pages = {1073-1083}, pmid = {35106672}, issn = {1432-5195}, mesh = {Adult ; Aged ; *Arthroscopy/adverse effects ; Elbow ; *Elbow Joint/surgery ; Female ; Humans ; Male ; Middle Aged ; Risk Factors ; }, abstract = {PURPOSE: To determine the complications from elbow arthroscopy for the past 16 years, and to summarize the most reported safety techniques and risk factors.

METHODS: Eligibility criteria included level I to IV evidence articles that were published after 2005 in the English language. Excluded were vet, paediatric, and cadaver studies. Open and arthroscopic-assisted elbow procedures were not included. Two online databases were comprehensively searched (PubMed and PMC) in April 2021. Relevant paper selection was conducted by two independent reviewers. MINORS score, demographic properties, indications, procedure type, complication rates, reoperation rates, reported risk factors, and safety techniques were recorded.

RESULTS: Fifty-two articles met the criteria and were included. No relevant level I to II evidence studies were discovered. The mean age ranged from 31 to 65 years. The average body mass indexes were between 26 and over 40 kg/m[2]. There was a prevalence of male sex (from 50.2 to 79.2%). Most of the studies reported a minimum follow-up (range, 4 weeks-12 months). The most common arthroscopic procedure was debridement (up to 73% in Leong et al.'s study). The average MINORS score was 12 (range, 10-16). The total complications rate ranged from 1.5 to 11%, with a few studies reporting over 25%. Nerve injury rate was 1.26-7.5%. Re-operation rate ranged from none (100 procedures) to 11.8%.

CONCLUSIONS: Elbow arthroscopy is a successful procedure with a low overall complications rate (from 1.5 to 11%), and a low nerve injury rate (from 1.26 to 7.5%). Risk factors include patient-related factors (obesity, female sex, age over 65 years, elevated blood sugar levels, hypercoagulable disorder, tobacco and alcohol use), preoperative elbow impairment/previous surgery, and periprocedural steroid injections. Our review discovered a re-operation rate of 2 to 18%.}, } @article {pmid35094642, year = {2023}, author = {Morse, N and Thomson, LJ and Elsden, E and Rogers, H and Chatterjee, HJ}, title = {Exploring the potential of creative museum-led activities to support stroke In-patient rehabilitation and wellbeing: A pilot mixed-methods study.}, journal = {Arts & health}, volume = {15}, number = {2}, pages = {135-152}, doi = {10.1080/17533015.2022.2032224}, pmid = {35094642}, issn = {1753-3023}, mesh = {Humans ; *Stroke Rehabilitation/methods ; Retrospective Studies ; Museums ; Pilot Projects ; *Stroke ; }, abstract = {BACKGROUND: This paper proposes a framework for studying the potential of museum-led interventions for supporting stroke rehabilitation goals.

METHODS: The intervention was based on Kirvevold et al.'s model for interventions for post-stroke wellbeing. Mixed-methods data wqas collected to review benefits in a pilot study, including retrospective video observations for six sessions with four patients; interviews with patients, carers and facilitators; pre-post patient assessments; and facilitator diaries.

RESULTS: Systematic analysis of videos showed high levels of concentration and engagement with museum objects, low levels of social interaction, and positive or neutral mood throughout. Thematic qualitative analysis suggested patients felt engaged in meaningful activities, which lifted negative mood, provided positive distraction from the ward, and increased self-esteem, including belief in patient abilities.

CONCLUSION: Further research is needed to fully establish the potential of museum-led interventions for stroke rehabilitation.}, } @article {pmid35083755, year = {2022}, author = {Williams, MN and Marques, MD and Hill, SR and Kerr, JR and Ling, M}, title = {Why are beliefs in different conspiracy theories positively correlated across individuals? Testing monological network versus unidimensional factor model explanations.}, journal = {The British journal of social psychology}, volume = {61}, number = {3}, pages = {1011-1031}, doi = {10.1111/bjso.12518}, pmid = {35083755}, issn = {2044-8309}, support = {RM22245//Massey University/ ; }, mesh = {Adult ; *Delusions/psychology ; Group Processes ; Humans ; Personality ; *Politics ; Self Concept ; United States ; }, abstract = {A substantial minority of the public express belief in conspiracy theories. A robust phenomenon in this area is that people who believe one conspiracy theory are more likely to believe in others. But the reason for this "positive manifold" of belief in conspiracy theories is unclear. One possibility is that a single underlying latent factor (e.g. "conspiracism") causes variation in belief in specific conspiracy theories. Another possibility is that beliefs in various conspiracy theories support one another in a mutually reinforcing network of beliefs (the "monological belief system" theory). While the monological theory has been influential in the literature, the fact that it can be operationalised as a statistical network model has not previously been recognised. In this study, we therefore tested both the unidimensional factor model and a network model. Participants were 1553 American adults recruited via Prolific. Belief in conspiracies was measured using an adapted version of the Belief in Conspiracy Theories Inventory. The fit of the two competing models was evaluated both by using van Bork et al.'s (Psychometrika, 83, 2018, 443, Multivariate Behavioral Research, 56, 2019, 175) method for testing network versus unidimensional factor models, as well as by evaluating goodness of fit to the sample covariance matrix. In both cases, evaluation of fit according to our pre-registered inferential criteria favoured the network model.}, } @article {pmid35073206, year = {2022}, author = {Sakamaki, T and Furusawa, Y and Hayashi, A and Otsuka, M and Fernandez, J}, title = {Remote Patient Monitoring for Neuropsychiatric Disorders: A Scoping Review of Current Trends and Future Perspectives from Recent Publications and Upcoming Clinical Trials.}, journal = {Telemedicine journal and e-health : the official journal of the American Telemedicine Association}, volume = {28}, number = {9}, pages = {1235-1250}, pmid = {35073206}, issn = {1556-3669}, mesh = {Clinical Trials as Topic ; *Epilepsy ; Humans ; Monitoring, Physiologic ; *Parkinson Disease/diagnosis/therapy ; *Telemedicine ; *Wearable Electronic Devices ; }, abstract = {Introduction: Telemedicine and remote patient monitoring are rapidly growing fields. This scoping review provides an update on remote patient monitoring for neuropsychiatric disorders from recent publications and upcoming clinical trials. Methods: Publications (PubMed and ICHUSHI; published January 2010 to February 2021) and trials (ClinicalTrials.gov and Japanese registries; active or recruiting by March 2021) that assessed wearable devices for remote management and/or monitoring of patients with neuropsychiatric disorders were searched. The review focuses on disorders with ≥3 publications. Results: We identified 44 publications and 51 active or recruiting trials, mostly from 2019 or 2020. Research on digital devices was most common for Parkinson's disease (11 publications and 19 trials), primarily for monitoring motor symptoms and/or preventing falls. Other disorders (3-5 publications each) included epilepsy (electroencephalogram [EEG] and seizure prediction), sleep disorder (sleep outcomes and behavioral therapies), multiple sclerosis (physical activity and symptoms), depression (physical activity, symptoms, and behavioral therapies), and amyotrophic lateral sclerosis (symptoms). Very few studies focused on newly emerging technologies (e.g., in-ear EEG and portable oximeters), and few studies integrated remote symptom monitoring with telemedicine. Discussion: Currently, development of digital devices for daily symptom monitoring is focused on Parkinson's disease. For the diseases reviewed, studies mostly focused on physical activity rather than psychiatric or nonmotor symptoms. Although the validity and usefulness of many devices are established, models for implementing remote patient monitoring in telehealth settings have not been established. Conclusions: Verification of the clinical effectiveness of digital devices combined with telemedicine is needed to further advance remote patient care for neuropsychiatric disorders.}, } @article {pmid35065536, year = {2021}, author = {Gurman, D and McCormick, CR and Klein, RM}, title = {Crossmodal Correspondence Between Auditory Timbre and Visual Shape.}, journal = {Multisensory research}, volume = {35}, number = {3}, pages = {221-241}, doi = {10.1163/22134808-bja10067}, pmid = {35065536}, issn = {2213-4808}, mesh = {Humans ; *Sound ; *Visual Perception ; }, abstract = {Crossmodal correspondences are defined as associations between crossmodal stimuli based on seemingly irrelevant stimulus features (i.e., bright shapes being associated with high-pitched sounds). There is a large body of research describing auditory crossmodal correspondences involving pitch and volume, but not so much involving auditory timbre, the character or quality of a sound. Adeli and colleagues (2014, Front. Hum. Neurosci. 8, 352) found evidence of correspondences between timbre and visual shape. The present study aimed to replicate Adeli et al.'s findings, as well as identify novel timbre-shape correspondences. Participants were tested using two computerized tasks: an association task, which involved matching shapes to presented sounds based on best perceived fit, and a semantic task, which involved rating shapes and sounds on a number of scales. The analysis of association matches reveals nonrandom selection, with certain stimulus pairs being selected at a much higher frequency. The harsh/jagged and smooth/soft correspondences observed by Adeli et al. were found to be associated with a high level of consistency. Additionally, high matching frequency of sounds with unstudied timbre characteristics suggests the existence of novel correspondences. Finally, the ability of the semantic task to supplement existing crossmodal correspondence assessments was demonstrated. Convergent analysis of the semantic and association data demonstrates that the two datasets are significantly correlated (-0.36) meaning stimulus pairs associated with a high level of consensus were more likely to hold similar perceived meaning. The results of this study are discussed in both theoretical and applied contexts.}, } @article {pmid35064820, year = {2022}, author = {Harder, LD and Miksha, RM}, title = {No statistical evidence that honey bees competitively reduced wild bee abundance in the Munich Botanic Garden-a comment on Renner et al. (2021).}, journal = {Oecologia}, volume = {198}, number = {2}, pages = {337-341}, pmid = {35064820}, issn = {1432-1939}, support = {RGPIN-2018-03907//Natural Sciences and Engineering Research Council of Canada/ ; }, mesh = {Animals ; *Bees/classification ; Competitive Behavior ; *Gardens ; Germany ; Plants ; }, abstract = {In a recent paper, Renner et al. (Oecologia 195:825-831, 2021) concluded, without supporting statistical evidence, that increased density of managed honey-bee hives between 2019 and 2020 intensified competitive effects of honey bees on non-Apis bee species in the Munich Botanic Garden. Analysis of Renner et al.'s observations revealed that, contrary to their assumption, the change in hive numbers did not statistically alter honey-bee visitation to 29 plant species within or between years. Given this consistency, changes in the proportion of non-Apis bees among visitors of the surveyed plant species between years likely represent their responses to reduced overall availability of floral resources during 2020. Thus, Renner et al.'s observations do not provide convincing evidence that honey bees competitively reduced the abundance of non-Apis bees in the Munich Botanic Garden.}, } @article {pmid35063250, year = {2022}, author = {Farina, MP}, title = {The importance of race and other social determinants of health for understanding cognitive health inequality found in Valdes et al.'s "Demographic and social determinants of cognitive dysfunction following hospitalization of COVID-19".}, journal = {Journal of the neurological sciences}, volume = {438}, number = {}, pages = {120151}, pmid = {35063250}, issn = {1878-5883}, mesh = {*COVID-19 ; Cognition ; *Cognitive Dysfunction/epidemiology/etiology ; Health Status Disparities ; Hospitalization ; Humans ; Social Determinants of Health ; Socioeconomic Factors ; }, } @article {pmid35047461, year = {2021}, author = {Ellis, C and Pease, A and Garstang, J and Watson, D and Blair, PS and Fleming, PJ}, title = {Interventions to Improve Safer Sleep Practices in Families With Children Considered to Be at Increased Risk for Sudden Unexpected Death in Infancy: A Systematic Review.}, journal = {Frontiers in pediatrics}, volume = {9}, number = {}, pages = {778186}, pmid = {35047461}, issn = {2296-2360}, abstract = {Background: Advice to families to follow infant care practices known to reduce the risks of Sudden Unexpected Death in Infancy (SUDI) has led to a reduction in deaths across the world. This reduction has slowed in the last decade with most deaths now occurring in families experiencing social and economic deprivation. A systematic review of the literature was commissioned by the National Child Safeguarding Practice Review Panel in England. The review covered three areas: interventions to improve engagement with support services, parental decision-making for the infant sleep environment, and interventions to improve safer sleep practices in families with infants considered to be at risk of SUDI. Aim: To describe the safer sleep interventions tested with families with infants at risk of SUDI and investigate what this literature can tell us about what works to reduce risk and embed safer sleep practices in this group. Methods: Eight online databases were systematically searched in December 2019. Intervention studies that targeted families with infants (0-1 year) at increased risk of SUDI were included. Studies were limited to those from Western Europe, North America or Australasia, published in the last 15 years. The Quality Assessment Tool for Studies with Diverse Designs was applied to assess quality. Data from included studies were extracted for narrative synthesis, including mode of delivery using Michie et al.'s Mode of Delivery Taxonomy. Results: The wider review returned 3,367 papers, with 23 intervention papers. Five types of intervention were identified: (1) infant sleep space and safer sleep education programs, (2) intensive or targeted home visiting services, (3) peer educators/ambassadors, (4) health education/raising awareness interventions, (5) targeted health education messages using digital media. Conclusion: Influencing behavior in families with infants at risk of SUDI has traditionally focused on "getting messages across," with interventions predominantly using education and awareness raising mechanisms. This review found evidence of interventions moving from "information giving" to "information exchange" models using personalized, longer term relationship-building models. This shift may represent an improvement in how safer sleep advice is implemented in families with infants at risk, but more robust evidence of effectiveness is required. Systematic Review Registration: https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/901091/DfE_Death_in_infancy_review.pdf, identifier: CRD42020165302.}, } @article {pmid35040381, year = {2022}, author = {Blanchard, R}, title = {A Novel Method for Studying the Effect of Older Brothers on Sexual Orientation and Its Robustness to Stopping Rule Distortions.}, journal = {Journal of sex research}, volume = {59}, number = {6}, pages = {684-689}, doi = {10.1080/00224499.2021.1984379}, pmid = {35040381}, issn = {1559-8519}, mesh = {Birth Order ; Child ; Female ; Homosexuality, Male ; Humans ; Kenya ; Male ; Research Design ; *Sex Workers ; Sexual Behavior ; *Siblings ; }, abstract = {In a recent article, Ablaza, Kabátek, and Perales describe a novel statistical methodology for studying the relation between sibship composition and sexual orientation, and they report the results of applying that methodology to a fresh sample. Research conducted for this commentary investigated whether Ablaza et al.'s method would be robust to the distorting effect of stopping rules, that is, quasi-rules that parents follow in deciding whether to have another child. Results obtained with an archived sample in which stopping rule distortion was known to be present indicated that their method probably is not robust to this particular problem. On another topic, it is argued that Ablaza et al.'s finding that older brothers increased the odds of homosexuality in women needs to be confirmed with further research, because past studies have been inconsistent in this regard. It is further argued that, even if an effect of older brothers on women's sexual orientation is confirmed, this would not necessarily falsify the hypothesis that maternal immunization underlies the effect of older brothers on men's sexual orientation. That hypothesis would need to be extended but not necessarily abandoned.}, } @article {pmid35040096, year = {2022}, author = {Smeele, HP and Dijkstra, RCH and Kimman, ML and van der Hulst, RRWJ and Tuinder, SMH}, title = {Patient-Reported Outcome Measures Used for Assessing Breast Sensation after Mastectomy: Not Fit for Purpose.}, journal = {The patient}, volume = {15}, number = {4}, pages = {435-444}, pmid = {35040096}, issn = {1178-1661}, mesh = {*Breast Neoplasms/psychology ; Female ; Humans ; *Mammaplasty/adverse effects/psychology ; Mastectomy/methods ; Patient Reported Outcome Measures ; Patient Satisfaction ; Quality of Life ; Sensation ; }, abstract = {AIMS: The aims of this review were (i) to evaluate whether patient-reported outcome measures used in clinical studies for assessing sensation after mastectomy and breast reconstruction are suitable for this purpose, and (ii) to explore whether any measures used for assessing sensation after non-oncologic breast surgery are worth modifying for use in post-mastectomy patients.

METHODS: PRISMA guidelines were followed (PROSPERO number CRD42020178066). We searched six databases for studies of oncologic (i.e., therapeutic, prophylactic, and reconstructive) and non-oncologic breast surgery (e.g., breast reduction) in which sensation was assessed with a patient-reported outcome measure. From the selected studies, we extracted eligible measures, evaluated their fitness for purpose, and summarized the content of sensation-specific items.

RESULTS: Of 6728 articles identified, we selected 135 studies that used 124 eligible patient-reported outcome measures. For 97% of these measures, details regarding development and measurement properties were unavailable. Four (3%) validated measures-the Sensory Disturbances subscale of the Breast Cancer Sequelae Cause Scales, the Discomfort subscale of the Breast Sensation Assessment Scale (BSAS), Didier et al.'s questionnaire for "Assessment of the patients' satisfaction with cosmetic results, physical and emotional impact of mastectomy", and the Breast Specific Pain subscale of the Breast Cancer Treatment Outcomes Scale (BCTOS)-each contain at least one item pertaining to breast sensation, but target different concepts of interest. In total, the measures feature 215 sensation-specific items, most of which concern symptom severity (97%) as opposed to impact on daily functioning (3%).

CONCLUSION: Patient-reported outcome measures used in clinical studies for assessing sensation after mastectomy and breast reconstruction are unsuitable for this purpose: they are either non-validated or non-specific. We failed to identify any measures for use in non-oncologic breast surgery populations worth modifying. To collect meaningful, patient-relevant data regarding sensation after mastectomy, it is pertinent that future clinical trials adopt psychometrically robust, specific patient-reported outcome measures.}, } @article {pmid35039104, year = {2022}, author = {Li, Z and Sturge-Apple, ML and Jones-Gordils, HR and Davies, PT}, title = {Sensory processing sensitivity behavior moderates the association between environmental harshness, unpredictability, and child socioemotional functioning.}, journal = {Development and psychopathology}, volume = {34}, number = {2}, pages = {675-688}, pmid = {35039104}, issn = {1469-2198}, support = {R01 HD087761/HD/NICHD NIH HHS/United States ; }, mesh = {Child ; Humans ; Child, Preschool ; *Parents ; *Perception ; Child Behavior/psychology ; }, abstract = {Building on Ellis et al.'s theorization for potent dimensions of environmental adversity, the present work sought to evaluate how environmental harshness and unpredictability might function directly and in interaction with child sensory processing sensitivity (SPS) to shape the development of child socioemotional functioning. Participants were 235 young children (Mage = 2.97 at the first measurement occasion) and their parents, who were followed for two consecutive annual measurement occasions. Child SPS was measured through behavioral observation across multiple tasks within the laboratory setting. Greater environmental unpredictability was significantly associated with the development of children's externalizing problems over a year only for children with high SPS. Follow-up analyses indicated that the unpredictability-x-SPS interaction was consistent with differential susceptibility, such that high SPS children showed greater increases in externalizing problems under high unpredictability, but also lower increases/greater decreases in externalizing problems under low unpredictability. Such association did not apply to children with low SPS.}, } @article {pmid35037705, year = {2022}, author = {Ost, AM}, title = {Age-at-death estimation from the auricular surface of the ilium: A test of a sex-specific component method.}, journal = {Journal of forensic sciences}, volume = {67}, number = {3}, pages = {868-876}, doi = {10.1111/1556-4029.14983}, pmid = {35037705}, issn = {1556-4029}, mesh = {Age Determination by Skeleton/methods ; Aged ; Female ; *Forensic Anthropology/methods ; Geroscience ; Humans ; *Ilium/anatomy & histology ; Male ; }, abstract = {Accurate age-at-death estimation is important for both paleodemographic studies and forensic casework. Although the auricular surface of the ilium is a well-validated skeletal indicator for aging studies, problems persist with identifying features that estimate age accurately in older individuals. This study tests the utility of one method, developed by Igarashi et al. (2005), which claims to estimate age more accurately in older individuals using a presence/absence scoring system for 13 auricular surface traits. Four hundred (400) individuals, aged 16-93 years, from the Hamann-Todd Collection were examined to test the performance of Igarashi et al.'s method in a North American sample. Pearson's product-moment correlation tests were performed for both the overall method and individual traits to assess correlation with chronological age. Eleven of the 13 traits showed statically significant correlations with chronological age, and nine were found to have higher correlations than originally reported. The method showed a tendency toward negative bias (i.e., a tendency to under-age individuals, particularly in the older age range). Models for both males and females and full and reduced models developed by Igarashi et al. were tested; the sex-pooled full model performed best, and the female full model performed most poorly. Although this method did not have significantly higher accuracy rates in a North American sample than other auricular surface methods, unique traits identified by Igarashi et al. did correlate with chronological age. In future studies, these traits should be investigated using different scoring systems (e.g., character states), as they show utility for aging research.}, } @article {pmid35032085, year = {2022}, author = {Ho, LYW and Kwong, EWY and Song, MS and Kawakami, A and Boo, S and Lai, CKY and Yamamoto-Mitani, N}, title = {Decision-making preferences on end-of-life care for older people: Exploration and comparison of Japan, the Hong Kong SAR and South Korea in East Asia.}, journal = {Journal of clinical nursing}, volume = {31}, number = {23-24}, pages = {3498-3509}, doi = {10.1111/jocn.16178}, pmid = {35032085}, issn = {1365-2702}, support = {//Univers Foundation/ ; }, mesh = {Aged ; Humans ; *Advance Care Planning ; Cross-Sectional Studies ; *Decision Making ; Asia, Eastern ; Hong Kong ; Japan ; Republic of Korea ; *Terminal Care/psychology ; Culture ; Independent Living/psychology ; *Patient Preference/psychology ; Personal Satisfaction ; *Family Relations/psychology ; Decision Making, Shared ; }, abstract = {AIMS AND OBJECTIVES: The aim of this study was to examine and compare decision-making preferences on end-of-life care for older people in Japan, the Hong Kong SAR and South Korea.

BACKGROUND: Cultural values and beliefs influence decision-making on end-of-life care.

DESIGN: A cross-sectional design was adopted.

METHODS: Community-dwelling people aged ≥65 with additional requirements were recruited in 2016-2017 in the three regions. Their decision-making preferences on end-of-life care were assessed using Pang et al.'s questionnaire. These preferences and their sociodemographic and personal experience variables were compared and analysed using univariate and multiple logistic regressions. The STROBE checklist was followed.

RESULTS: This study involved 415 participants. In all three regions, the most preferred decision maker and person with whom to discuss end-of-life care issues was a family member. Participants in the Hong Kong SAR were less likely to select a family member as their preferred decision maker than those in Japan (adjusted odds ratio = 0.129). Koreans were less likely to discuss end-of-life care issues with medical professionals than people in Japan (adjusted odds ratio = 0.278). More than 70% of the participants in each region indicated that they would not prefer to leave an advance directive to decide their end-of-life care.

CONCLUSION: Older Asians prefer to make their own decisions after consulting others. Family members play an important role in helping older people plan their preferred end-of-life care arrangements, even acting as decision makers when older people become incapable of deciding for themselves.

Sufficient information should be provided to older people and their families for the older people to determine their preferred care. Helping families to understand and support the planned care and advance directives is a strategy for maximising family compliance with the care. Continuous efforts should be made to promote advance care planning and advance directives.}, } @article {pmid35026693, year = {2022}, author = {Vorms, M and Harris, AJL and Topf, S and Hahn, U}, title = {Plausibility matters: A challenge to Gilbert's "Spinozan" account of belief formation.}, journal = {Cognition}, volume = {220}, number = {}, pages = {104990}, doi = {10.1016/j.cognition.2021.104990}, pmid = {35026693}, issn = {1873-7838}, mesh = {Bilirubin ; *Gilbert Disease ; Glucuronosyltransferase ; Humans ; }, abstract = {Most of the claims we encounter in real life can be assigned some degree of plausibility, even if they are new to us. On Gilbert's (1991) influential account of belief formation, whereby understanding a sentence implies representing it as true, all new propositions are initially accepted, before any assessment of their veracity. As a result, plausibility cannot have any role in initial belief formation on this account. In order to isolate belief formation experimentally, Gilbert, Krull, and Malone (1990) employed a dual-task design: if a secondary task disrupts participants' evaluation of novel claims presented to them, then the initial encoding should be all there is, and if that initial encoding consistently renders claims 'true' (even where participants were told in the learning phase that the claims they had seen were false), then Gilbert's account is confirmed. In this pre-registered study, we replicate one of Gilbert et al.'s (1990) seminal studies ("The Hopi Language Experiment") while additionally introducing a plausibility variable. Our results show that Gilbert's 'truth bias' does not hold for implausible statements - instead, initial encoding seemingly renders implausible statements 'false'. As alternative explanations of this finding that would be compatible with Gilbert's account can be ruled out, it questions Gilbert's account.}, } @article {pmid35026441, year = {2022}, author = {DeLisi, M and Drury, AJ and Elbert, MJ}, title = {The p factor, crime, and criminal justice: A criminological study of Caspi et al.'s general psychopathology general theory.}, journal = {International journal of law and psychiatry}, volume = {81}, number = {}, pages = {101773}, doi = {10.1016/j.ijlp.2021.101773}, pmid = {35026441}, issn = {1873-6386}, mesh = {Crime ; Criminal Law ; *Criminals ; Criminology ; Humans ; *Substance-Related Disorders/epidemiology ; }, abstract = {The general psychopathology general theory or p Factor is an influential theoretical development in the social and behavioral sciences, but has yet to gain traction in criminology and criminal justice. Drawing on data from a sample of 1722 federal pretrial defendants, we created a 22-item composite indicator or additive index of the p Factor containing externalizing, internalizing, substance use, paraphilic, and forensic indicators. Negative binomial regression models found that age, sex, and diverse forms of trauma exposure are associated with higher p Factor scores. Higher p scores strongly predicted total, violent, sexual, property, weapon, and drug arrest charges net the effects of demographic features and adverse childhood experiences. There is broad heterogeneity in psychopathology within this sample with nearly 29% of clients exhibiting zero psychopathology, nearly 61% showing average psychopathology or less, and nearly 40% evincing average to exceedingly high psychopathology. As a general theory, the p Factor has considerable potential to inform the assorted morbidities that often accompany criminal activity, including self-harm, reduced global functioning, substance use, and social dysfunction and thus is a parsimonious conceptual framework to understand the overlapping and systemic personal problems that typify chronic and serious criminal offenders.}, } @article {pmid35025549, year = {2022}, author = {Fragaszy, DM}, title = {End the search quickly: Pigeons (Columba livia) and humans (Homo sapiens) share the same bias.}, journal = {Journal of comparative psychology (Washington, D.C. : 1983)}, volume = {136}, number = {1}, pages = {1-2}, doi = {10.1037/com0000311}, pmid = {35025549}, issn = {1939-2087}, mesh = {Animals ; *Choice Behavior ; *Columbidae ; Humans ; Reinforcement, Psychology ; Research Design ; Reward ; }, abstract = {Comments on an article by W. T. Herbranson et al. (see record 2022-07304-001). The article by Herbranson et al. illustrates the care that must be taken, both in designing comparative research and in interpreting the findings, to understand how specific features of experimental design impact each species' choices. Herbranson et al. presented to pigeons a decision-making challenge known informally as "The Secretary Problem", a problem cast in the form of selecting a candidate for a job. The task is to make a single choice among a finite set of options when these options are presented in succession. The chooser must select a given option or pass on to the next without knowing what the remaining options are. Decisions are final-one either rejects an option when it appears or selects that option, ending the search. The authors trained pigeons to recognize the "reward value" of five different colors on keys that they could peck. Herbranson et al. subsequently replicated the study with humans, presenting humans with probabilistic outcomes (rather than the certain outcomes of varying value presented in earlier studies with humans). Their aim was to explore the consequences of altering reinforcement options on humans' choices, so as to understand more fully the ways in which pigeons and humans approach this problem. Herbranson et al.'s work is an example of the power of carefully constructed comparative behavioral experiments to expand the understanding of ourselves and other species in unexpected ways. (PsycInfo Database Record (c) 2022 APA, all rights reserved).}, } @article {pmid35023333, year = {2022}, author = {Figueroa, KC and Song, B and Sunny, S and Li, S and Gurushanth, K and Mendonca, P and Mukhia, N and Patrick, S and Gurudath, S and Raghavan, S and Imchen, T and Leivon, ST and Kolur, T and Shetty, V and Bushan, V and Ramesh, R and Pillai, V and Wilder-Smith, P and Sigamani, A and Suresh, A and Kuriakose, MA and Birur, P and Liang, R}, title = {Interpretable deep learning approach for oral cancer classification using guided attention inference network.}, journal = {Journal of biomedical optics}, volume = {27}, number = {1}, pages = {}, pmid = {35023333}, issn = {1560-2281}, support = {R44 CA265514/CA/NCI NIH HHS/United States ; UH2 EB022623/EB/NIBIB NIH HHS/United States ; R03 EB014852/EB/NIBIB NIH HHS/United States ; UH3 CA239682/CA/NCI NIH HHS/United States ; R21 CA087527/CA/NCI NIH HHS/United States ; R01 DE030682/DE/NIDCR NIH HHS/United States ; UL1 TR001414/TR/NCATS NIH HHS/United States ; P41 RR001192/RR/NCRR NIH HHS/United States ; P30 CA062203/CA/NCI NIH HHS/United States ; }, mesh = {Attention ; *Deep Learning ; Humans ; *Mouth Neoplasms/diagnostic imaging ; Neural Networks, Computer ; Reproducibility of Results ; }, abstract = {SIGNIFICANCE: Convolutional neural networks (CNNs) show the potential for automated classification of different cancer lesions. However, their lack of interpretability and explainability makes CNNs less than understandable. Furthermore, CNNs may incorrectly concentrate on other areas surrounding the salient object, rather than the network's attention focusing directly on the object to be recognized, as the network has no incentive to focus solely on the correct subjects to be detected. This inhibits the reliability of CNNs, especially for biomedical applications.

AIM: Develop a deep learning training approach that could provide understandability to its predictions and directly guide the network to concentrate its attention and accurately delineate cancerous regions of the image.

APPROACH: We utilized Selvaraju et al.'s gradient-weighted class activation mapping to inject interpretability and explainability into CNNs. We adopted a two-stage training process with data augmentation techniques and Li et al.'s guided attention inference network (GAIN) to train images captured using our customized mobile oral screening devices. The GAIN architecture consists of three streams of network training: classification stream, attention mining stream, and bounding box stream. By adopting the GAIN training architecture, we jointly optimized the classification and segmentation accuracy of our CNN by treating these attention maps as reliable priors to develop attention maps with more complete and accurate segmentation.

RESULTS: The network's attention map will help us to actively understand what the network is focusing on and looking at during its decision-making process. The results also show that the proposed method could guide the trained neural network to highlight and focus its attention on the correct lesion areas in the images when making a decision, rather than focusing its attention on relevant yet incorrect regions.

CONCLUSIONS: We demonstrate the effectiveness of our approach for more interpretable and reliable oral potentially malignant lesion and malignant lesion classification.}, } @article {pmid35014056, year = {2022}, author = {Vogel, M and Krüger, J and Junne, F}, title = {Eating disorder related research using Amazon Mechanical Turk (MTurk): Friend or foe?: Commentary on Burnette et al. (2021).}, journal = {The International journal of eating disorders}, volume = {55}, number = {2}, pages = {285-287}, doi = {10.1002/eat.23675}, pmid = {35014056}, issn = {1098-108X}, mesh = {*COVID-19 ; *Crowdsourcing ; *Feeding and Eating Disorders ; Humans ; Pandemics ; SARS-CoV-2 ; Surveys and Questionnaires ; }, abstract = {Burnette et al. reported a study that they sought to undertake to validate common eating disorder questionnaires in sexual and gender minorities. The researchers took advantage of the online recruitment platform Amazon Mechanical Turk (MTurk). Contrary to their expectations, the study proved not feasible due to invalid answering. Thus, Burnette et al. raise concerns against the trustworthiness of crowd-sourced data that may be undermined by financial interests and other kinds of motivations. Our commentary highlights the potential of the COVID-19 pandemic to inflate especially those intentions, which are monetary. Against the background of the COVID-19 pandemic, a further problem seems to be that the anonymity of online crowd sourcing platforms might tempt participants to provide inconsistent answers, possibly reflecting tendencies of reactance. The reported pattern of paradoxical responses in Burnette et al.'s work does not reflect malingering; rather we believe that the study might have served some participants as an outlet for negative emotions. We discuss mechanisms of quality control and highlight the lack of interpersonal interaction associated with online data collections.}, } @article {pmid35007773, year = {2022}, author = {Kalogerakis, GC and Boparai, HK and Yang, MI and Sleep, BE}, title = {A high-throughput and cost-effective microplate reader method for measuring persulfates (peroxydisulfate and peroxymonosulfate).}, journal = {Talanta}, volume = {240}, number = {}, pages = {123170}, doi = {10.1016/j.talanta.2021.123170}, pmid = {35007773}, issn = {1873-3573}, mesh = {Cost-Benefit Analysis ; *Groundwater ; Oxidants ; *Peroxides ; }, abstract = {Frequent use of persulfates as oxidants, for in situ chemical oxidation and advanced oxidation processes, warrants the need for developing a fast and efficient method for measuring persulfate concentrations in aqueous samples in the lab and on site. Here, we propose a modified method, based on Liang et al.'s (2008) spectrophotometric method, for measuring both peroxydisulfate (PDS) and peroxymonosulfate (PMS) in the aqueous samples. Our method involves a deep 96-well plate, multi-channel pipettes, a small orbital shaker, and a microplate reader; allowing the preparation and analysis of up to 96 samples in one run. Our proposed method shortens the time by 10 folds, consumes only ∼2% of the original reagents, and generates only ∼2% of the liquid waste compared to the Liang et al.'s method, thus, making our method high-throughput, time-efficient, and cost-effective with reduced environmental impact. The presented microplate reader method is validated in terms of linearity, LOD, LOQ, accuracy, precision, robustness, and selectivity. All the parameters satisfied the acceptance criteria, according to ICH guidelines. The linearity of calibration curves was evaluated by performing the F-test. In general, our method has linear ranges from 20 to 42,000 and 5 to 40,960 μM for PDS and PMS, respectively. Accuracy (% recovery) results suggested that the LOD and LOQ based on the standard deviation of y-intercepts of the regression lines were the most reliable. The LOD/LOQ values for PDS and PMS were 14.7/44.1 and 4.6/14.4 μM, respectively. The proposed method was also modified to work with a standard cuvette spectrophotometer and was validated. A comparison with the UHPLC analysis of PDS showed that our microplate reader method performed equivalently or even outperformed the UHPLC method, in the presence of common groundwater constituents and organic contaminants.}, } @article {pmid34999509, year = {2022}, author = {Grand-Guillaume-Perrenoud, JA and Origlia, P and Cignacco, E}, title = {Barriers and facilitators of maternal healthcare utilisation in the perinatal period among women with social disadvantage: A theory-guided systematic review.}, journal = {Midwifery}, volume = {105}, number = {}, pages = {103237}, doi = {10.1016/j.midw.2021.103237}, pmid = {34999509}, issn = {1532-3099}, mesh = {Female ; Health Services Accessibility ; Humans ; *Maternal Health Services ; Parturition ; Patient Acceptance of Health Care ; Pregnancy ; Qualitative Research ; }, abstract = {BACKGROUND: Women with social disadvantage have poorer perinatal outcomes compared to women in advantaged social positions, which may be linked to poorer healthcare utilisation. Disadvantaged groups may experience a greater diversity of barriers (e.g., feeling embarrassed about pregnancy, lack of transportation) or barriers judged to be particularly difficult (e.g., embarrassment about pregnancy). They may also experience barriers more frequently (e.g., depression). Using Levesque et al.'s (2013) framework of healthcare access, our review identifies the barriers and facilitators that affect maternal healthcare utilisation in the perinatal period among women with social disadvantage in high-income nations.

OBJECTIVES: Our review searches for the barriers and facilitators affecting maternal healthcare utilisation in the perinatal period, from pregnancy to the first year postpartum, among women with social disadvantage (Prospero registration CRD42020151506).

DESIGN: We conducted a theory-guided systematic review. PubMed, Embase, MEDLINE, PsycINFO, and Social Science Citation Index databases were searched for publications between 1999 and 2018.

FINDINGS: 37 articles out of 12'972 were included in the qualitative synthesis. 19 domains of barriers and facilitators were extracted. Domains on the provider side includes 'information regarding available treatments' and 'trustful relationships.' On the user-side, domains include 'awareness of pregnancy' and 'unplanned/unwanted pregnancy' KEY CONCLUSIONS: Provider- and user-side characteristics interact to affect access. User-side characteristics that pose a barrier can be offset by provider-side characteristics that lower barriers to access.

IMPLICATIONS FOR PRACTICE: User-side characteristics (e.g., lack of awareness of pregnancy) play an important role in the initial steps toward access. Among women with social disadvantage, reducing barriers may require active outreach on the part of providers.}, } @article {pmid34990173, year = {2021}, author = {Lyon, AR and Brewer, SK and Areán, PA}, title = {Collaboratively maximizing the impact of human-centered design in psychological and implementation science: Reply to Proctor et al. (2021).}, journal = {The American psychologist}, volume = {76}, number = {7}, pages = {1189-1190}, pmid = {34990173}, issn = {1935-990X}, support = {F32 MH116623/MH/NIMH NIH HHS/United States ; P50 MH115837/MH/NIMH NIH HHS/United States ; R34 MH109605/MH/NIMH NIH HHS/United States ; }, mesh = {Humans ; *Implementation Science ; }, abstract = {Proctor et al.'s (2021) comment "Division 21 Has Been Devoted to Human-Centered Design Since the 1950s" on our article (Lyon et al., 2020) is a welcome addition and useful touchpoint surrounding the historical and current relationship between human-centered design and psychological science. "Siloing" in psychology inhibits the progress of the discipline. We offer a set of recommendations for reducing silos and increasing the integration of engineering psychology with implementation science to advance human-centered design and the use of research evidence in practice. (PsycInfo Database Record (c) 2022 APA, all rights reserved).}, } @article {pmid34988279, year = {2021}, author = {Simandan, D}, title = {Social capital, population health, and the gendered statistics of cardiovascular and all-cause mortality.}, journal = {SSM - population health}, volume = {16}, number = {}, pages = {100971}, pmid = {34988279}, issn = {2352-8273}, abstract = {Scholars in the field of population health need to be on the constant lookout for the danger that their tacit ideological commitments translate into systematic biases in how they interpret their empirical results. This contribution illustrates this problematic by critically interrogating a set of concepts such as tradition, trust, social capital, community, or gender, that are routinely used in population health research even though they carry a barely acknowledged political and ideological load. Alongside this wider deconstruction of loaded concepts, I engage critically but constructively with Martin Lindström et al.'s paper "Social capital, the miniaturization of community, traditionalism and mortality: A population-based prospective cohort study in southern Sweden" to evaluate the extent to which it fits with other empirical findings in the extant literature. Taking as a point of departure the intriguing finding that social capital predicts cardiovascular and all-cause mortality only for men, but not for women, I argue that future research on the nexus of social capital, health, and mortality needs to frame gender not only as a demographic and statistical variable, but also as an ontological conundrum and as an epistemological sensibility.}, } @article {pmid34987373, year = {2021}, author = {Fan, R and Gao, Y and Zhang, H and Xin, X and Sang, F and Tan, Z and Zhang, B and Li, X and Huang, X and Li, S and Chang, J}, title = {Lesion Distribution and Early Changes of Right Hemisphere in Chinese Patients With Post-stroke Aphasia.}, journal = {Frontiers in aging neuroscience}, volume = {13}, number = {}, pages = {632217}, pmid = {34987373}, issn = {1663-4365}, abstract = {The role of the right hemisphere (RH) in post-stroke aphasia (PSA) has not been completely understood. In general, the language alterations in PSA are normally evaluated from the perspective of the language processing models developed from Western languages such as English. However, the successful application of the models for assessing Chinese-language functions in patients with PSA has not been reported. In this study, the features of specific language-related lesion distribution and early variations of structure in RH in Chinese patients with PSA were investigated. Forty-two aphasic patients (female: 13, male: 29, mean age: 58 ± 12 years) with left hemisphere (LH) injury between 1 and 6 months after stroke were included. The morphological characteristics, both at the levels of gray matter (GM) and white matter (WM), were quantified by 3T multiparametric brain MRI. The Fridriksson et al.'s dual-stream model was used to compare language-related lesion regions. Voxel-based lesion-symptom mapping (VLSM) analysis has been performed. Our results showed that lesions in the precentral, superior frontal, middle frontal, and postcentral gyri were responsible for both the production and comprehension dysfunction of Chinese patients with PSA and were quite different from the lesions described by using the dual-stream model of Fridriksson et al. Furthermore, gray matter volume (GMV) was found significantly decreased in RH, and WM integrity was disturbed in RH after LH injury in Chinese patients with PSA. The different lesion patterns between Chinese patients with PSA and English-speaking patients with PSA may indicate that the dual-stream model of Fridriksson et al. is not suitable for the assessment of Chinese-language functions in Chinese patients with PSA in subacute phase of recovery. Moreover, decreased structural integrity in RH was found in Chinese patients with PSA.}, } @article {pmid34983502, year = {2022}, author = {Beiranvand, S and Mohammad Khan Kermanshahi, S and Memarian, R and Almasian, M}, title = {From clinical expert nurse to part-time clinical nursing instructor: design and evaluation of a competency-based curriculum with structured mentoring: a mixed methods study.}, journal = {BMC nursing}, volume = {21}, number = {1}, pages = {10}, pmid = {34983502}, issn = {1472-6955}, abstract = {BACKGROUND: Transition from a clinical expert nurse to a part time clinical nursing instructor (PTCNI) poses several challenges. Designing a professional development curriculum to facilitate the transition from a clinical expert nurse to a PTCNI is critical to effective education. A comprehensive competency-based curriculum was developed and implemented with structured mentoring to prepare clinical expert nurses as PTCNIs.

METHODS: A mixed-methods study with a sequential-exploratory approach was conducted in Iran in 2019. In the qualitative phase, Saylor et al.'s (1981) seven-step model was used, consisting of (1) collecting evidence from a systematic review, (2) conducting interviews with learners, (3) setting goals and objectives, (4) design, (5) implementation, (6) evaluation, and (7) feedback. In the quantitative phase, curriculum domains were evaluated. Additionally, the effective professional communication skills module was implemented using a quasi-experimental study with a pre-test post-test single-group design for 5 PTCNIs in a pilot study.

RESULTS: After integrating the findings of the literature review and field interviews in the analysis stage, a curriculum was developed with a total of 150 h, six modules, and 24 topics. Results of the pilot study showed a significant improvement in the confidence of PTCNIs as a result of the implementation of the effective communication skills module using the mentoring method (t = - 16.554, p = 0.0005).

CONCLUSIONS: This competency-based curriculum was based on the evidence and needs of PTCNIs and provides a complete coverage of their clinical education competencies. It is suggested that managers of educational institutes that offer nursing programs use this curriculum to prepare them in continuing education programs. Further studies are needed to thoroughly evaluate the learning outcomes for students.}, } @article {pmid34981890, year = {2022}, author = {Sangari, S and Peyre, I and Lackmy-Vallée, A and Bayen, E and Pradat, PF and Marchand-Pauvert, V}, title = {Transient increase in recurrent inhibition in amyotrophic lateral sclerosis as a putative protection from neurodegeneration.}, journal = {Acta physiologica (Oxford, England)}, volume = {234}, number = {4}, pages = {e13758}, doi = {10.1111/apha.13758}, pmid = {34981890}, issn = {1748-1716}, mesh = {*Amyotrophic Lateral Sclerosis ; Humans ; Motor Neurons/physiology ; Neural Inhibition/physiology ; *Renshaw Cells ; Spinal Cord/physiology ; }, abstract = {AIM: Adaptive mechanisms in spinal circuits are likely involved in homeostatic responses to maintain motor output in amyotrophic lateral sclerosis. Given the role of Renshaw cells in regulating the motoneuron input/output gain, we investigated the modulation of heteronymous recurrent inhibition.

METHODS: Electrical stimulations were used to activate recurrent collaterals resulting in the Hoffmann reflex depression. Inhibitions from soleus motor axons to quadriceps motoneurons, and vice versa, were tested in 38 patients and matched group of 42 controls.

RESULTS: Compared with controls, the mean depression of quadriceps reflex was larger in patients, while that of soleus was smaller, suggesting that heteronymous recurrent inhibition was enhanced in quadriceps but reduced in soleus. The modulation of recurrent inhibition was linked to the size of maximal direct motor response and lower limb dysfunctions, suggesting a significant relationship with the integrity of the target motoneuron pool and functional abilities. No significant link was found between the integrity of motor axons activating Renshaw cells and the level of inhibition. Enhanced inhibition was particularly observed in patients within the first year after symptom onset and with slow progression of lower limb dysfunctions. Normal or reduced inhibitions were mainly observed in patients with motor weakness first in lower limbs and greater dysfunctions in lower limbs.

CONCLUSION: We provide the first evidence for enhanced recurrent inhibition and speculate that Renshaw cells might have transient protective role on motoneuron by counteracting hyperexcitability at early stages. Several mechanisms likely participate including cortical influence on Renshaw cell and reinnervation by slow motoneurons.}, } @article {pmid34962275, year = {2022}, author = {Lin, WY}, title = {Genome-wide association study for four measures of epigenetic age acceleration and two epigenetic surrogate markers using DNA methylation data from Taiwan Biobank.}, journal = {Human molecular genetics}, volume = {31}, number = {11}, pages = {1860-1870}, doi = {10.1093/hmg/ddab369}, pmid = {34962275}, issn = {1460-2083}, mesh = {Aging/genetics ; Biological Specimen Banks ; Biomarkers/metabolism ; *DNA Methylation/genetics ; Epigenesis, Genetic ; *Genome-Wide Association Study/methods ; Humans ; Taiwan ; }, abstract = {To highlight the genetic architecture for epigenetic aging, McCartney et al. recently identified 137 significant single-nucleotide polymorphisms based on genome-wide association study (GWAS) meta-analyses of four epigenetic clocks and two epigenetic surrogate markers. However, none Asian ancestry studies have been included in this or previous meta-analyses. I performed a GWAS on blood DNA methylation (DNAm) levels of 2309 Taiwan Biobank (TWB) participants. Owing to the fact that the sample size of an individual GWAS of DNAm data is still not large, I adopted the 'prioritized subset analysis' (PSA) method to boost the power of a GWAS. The four epigenetic clocks and the two epigenetic surrogate markers were investigated, respectively. I replicated 21 out of the 137 aging-associated genetic loci by applying the PSA method to the TWB DNAm data. Moreover, I identified five novel loci, including rs117530284 that was associated with the 'epigenetic age acceleration' (EAA) according to Lu et al.'s GrimAge (called 'GrimEAA'). Considering 16 covariates (sex, BMI, smoking status, drinking status, regular exercise, educational attainment and the first 10 ancestry principal components), each 'A' allele of rs117530284 in the IBA57 gene was found to be associated with a 1.5943-year GrimEAA (95% confidence interval = [1.0748, 2.1138]). IBA57 is a protein coding gene and is associated with multiple mitochondrial dysfunctions syndromes. A decline in mitochondrial activity and quality is associated with aging and many age-related diseases. This is one of the first DNAm GWAS for individuals of Asian ancestry.}, } @article {pmid34960353, year = {2021}, author = {Breasail, MÓ and Biswas, B and Smith, MD and Mazhar, MKA and Tenison, E and Cullen, A and Lithander, FE and Roudaut, A and Henderson, EJ}, title = {Wearable GPS and Accelerometer Technologies for Monitoring Mobility and Physical Activity in Neurodegenerative Disorders: A Systematic Review.}, journal = {Sensors (Basel, Switzerland)}, volume = {21}, number = {24}, pages = {}, pmid = {34960353}, issn = {1424-8220}, support = {GAT3676//The Gatsby Foundation/ ; }, mesh = {Accelerometry ; Exercise ; Geographic Information Systems ; Humans ; *Neurodegenerative Diseases ; Technology ; *Wearable Electronic Devices ; }, abstract = {Neurodegenerative disorders (NDDs) constitute an increasing global burden and can significantly impair an individual's mobility, physical activity (PA), and independence. Remote monitoring has been difficult without relying on diaries/questionnaires which are more challenging for people with dementia to complete. Wearable global positioning system (GPS) sensors and accelerometers present a cost-effective and noninvasive way to passively monitor mobility and PA. In addition, changes in sensor-derived outcomes (such as walking behaviour, sedentary, and active activity) may serve as potential biomarkers of disease onset, progression, and response to treatment. We performed a systematic search across four databases to identify papers published within the past 5 years, in which wearable GPS or accelerometers were used to monitor mobility or PA in patients with common NDDs (Parkinson's disease, Alzheimer's disease, motor neuron diseases/amyotrophic lateral sclerosis, vascular parkinsonism, and vascular dementia). Disease and technology-specific vocabulary were searched singly, and then in combination, identifying 4985 papers. Following deduplication, we screened 3115 papers and retained 28 studies following a full text review. One study used wearable GPS and accelerometers, while 27 studies used solely accelerometers in NDDs. GPS-derived measures had been validated against current gold standard measures in one Parkinson's cohort, suggesting that the technology may be applicable to other NDDs. In contrast, accelerometers are widely utilised in NDDs and have been operationalised in well-designed clinical trials.}, } @article {pmid34958154, year = {2022}, author = {Lozada, FT and Riley, TN and Catherine, E and Brown, DW}, title = {Black Emotions Matter: Understanding the Impact of Racial Oppression on Black Youth's Emotional Development: Dismantling Systems of Racism and Oppression During Adolescence: Dismantling Systems of Racism and Oppression During Adolescence.}, journal = {Journal of research on adolescence : the official journal of the Society for Research on Adolescence}, volume = {32}, number = {1}, pages = {13-33}, doi = {10.1111/jora.12699}, pmid = {34958154}, issn = {1532-7795}, mesh = {Adolescent ; Black or African American/psychology ; Emotions ; Humans ; Racial Groups ; *Racism/psychology ; Socialization ; United States ; }, abstract = {Black US Americans' emotions are subject to stereotypes about the anger and aggression of Black people. These stereotypes are readily applied to Black adolescents' emotions. The purpose of this conceptual paper is to operationalize racial oppression in the emotional lives of Black adolescents through an application of García Coll et al.'s (1996) ecological model for minority youth development. We specify emotionally inhibitive features of Black adolescents' schools, the adaptive culture of Black Americans in the United States that responds to emotional inhibition, Black families' emotion socialization processes, and Black adolescents' emotional flexibility behaviors. Throughout, we integrate findings from research on Black adolescents' emotional adjustment with research on cultural values, emotion and racial socialization, school-based racial experiences, and theory on emotion and cultural navigation.}, } @article {pmid34952487, year = {2022}, author = {Portnow, LH and Georgian-Smith, D and Haider, I and Barrios, M and Bay, CP and Nelson, KP and Raza, S}, title = {Persistent inter-observer variability of breast density assessment using BI-RADS® 5th edition guidelines.}, journal = {Clinical imaging}, volume = {83}, number = {}, pages = {21-27}, pmid = {34952487}, issn = {1873-4499}, support = {R01 CA172463/CA/NCI NIH HHS/United States ; R01 CA226805/CA/NCI NIH HHS/United States ; }, mesh = {*Breast Density ; *Breast Neoplasms/diagnostic imaging ; Female ; Humans ; Mammography/methods ; Observer Variation ; Radiologists ; }, abstract = {OBJECTIVES: Due to most states' legislation, mammographic density categorization has potentially far-reaching implications, but remains subjective based on BIRADS® guidelines. We aimed to determine 1) effect of BI-RADS® 5th edition (5th-ed) vs 4th-edition (4th-ed) guidelines on reader agreement regarding density assessment; 2) 5th-ed vs 4th-ed density distribution, and visual vs quantitative assessment agreement; 3) agreement between experienced vs less experienced readers.

METHODS: In a retrospective review, six breast imaging radiologists (BIR) (23-30 years' experience) visually assessed density of 200 screening mammograms performed September 2012-January 2013 using 5th-ed guidelines. Results were compared to 2016 data of the same readers evaluating the same mammograms using 4th-ed guidelines after a training module. 5th-ed density categorization by seven junior BIR (1-5 years' experience) was compared to eight experienced BIR. Nelson et al.'s kappas (κm, κw), Fleiss' κF, and Cohen's κ were calculated. Quantitative density using Volpara was compared with reader assessments.

RESULTS: Inter-reader weighted agreement using 5th-ed is moderately strong, 0.73 (κw, s.e. = 0.01), similar to 4th-ed, 0.71 (κw, s.e. = 0.03). Intra-reader Cohen's κ is 0.23-0.34, similar to 4th-ed. Binary not-dense vs dense categorization, using 5th-ed results in higher dense categorization vs 4th-ed (p < 0.001). 5th-ed density distribution results in higher numbers in categories B/C vs 4th-ed (p < 0.001). Distribution for 5th-ed does not differ based on reader experience (p = 0.09). Reader vs quantitative weighted agreement is similar (5th-ed, Cohen's κ = 0.76-0.85; 4th-ed, Cohen's κ = 0.68-0.83).

CONCLUSION: There is persistent subjectivity of visually assessed mammographic density using 5th-ed guidelines; experience does not correlate with better inter-reader agreement.}, } @article {pmid34950720, year = {2021}, author = {Qiu, M and Wei, XB and Wei, W}, title = {SGLT2is vs. GLP1RAs Reduce Cardiovascular and All-Cause Mortality.}, journal = {Frontiers in cardiovascular medicine}, volume = {8}, number = {}, pages = {791311}, pmid = {34950720}, issn = {2297-055X}, abstract = {Lin et al. recently did a network meta-analysis based on cardiovascular (CV) outcome trials (CVOTs) of sodium-glucose cotransporter 2 inhibitors (SGLT2is) and those of glucagon-like peptide-1 receptor agonists (GLP1RAs). Due to the absence of CVOTs directly comparing SGLT2is with GLP1RAs, Lin et al.'s network meta-analysis identified the indirect evidence that SGLT2is vs. GLP1RAs reduced hospitalization for heart failure (HHF) but did not reduce CV death and all-cause mortality (ACM) in patients with type 2 diabetes (T2D). We did another meta-analysis incorporating those CV outcome cohort studies directly comparing SGLT2is with GLP1RAs, and identified that SGLT2is vs. GLP1RAs were significantly associated with the lower risks of not only HHF but also CV death and ACM. These findings may suggest that SGLT2is should be considered over GLP1RAs in terms of preventing CV and all-cause death and HHF in T2D patients.}, } @article {pmid34900230, year = {2021}, author = {Vasilopoulou, C and Wingfield, B and Morris, AP and Duddy, W}, title = {snpQT: flexible, reproducible, and comprehensive quality control and imputation of genomic data.}, journal = {F1000Research}, volume = {10}, number = {}, pages = {567}, pmid = {34900230}, issn = {2046-1402}, mesh = {*Genome ; *Genomics ; Humans ; Quality Control ; Reproducibility of Results ; Software ; }, abstract = {Quality control of genomic data is an essential but complicated multi-step procedure, often requiring separate installation and expert familiarity with a combination of different bioinformatics tools. Software incompatibilities, and inconsistencies across computing environments, are recurrent challenges, leading to poor reproducibility. Existing semi-automated or automated solutions lack comprehensive quality checks, flexible workflow architecture, and user control. To address these challenges, we have developed snpQT: a scalable, stand-alone software pipeline using nextflow and BioContainers, for comprehensive, reproducible and interactive quality control of human genomic data. snpQT offers some 36 discrete quality filters or correction steps in a complete standardised pipeline, producing graphical reports to demonstrate the state of data before and after each quality control procedure. This includes human genome build conversion, population stratification against data from the 1,000 Genomes Project, automated population outlier removal, and built-in imputation with its own pre- and post- quality controls. Common input formats are used, and a synthetic dataset and comprehensive online tutorial are provided for testing, educational purposes, and demonstration. The snpQT pipeline is designed to run with minimal user input and coding experience; quality control steps are implemented with numerous user-modifiable thresholds, and workflows can be flexibly combined in custom combinations. snpQT is open source and freely available at https://github.com/nebfield/snpQT. A comprehensive online tutorial and installation guide is provided through to GWAS (https://snpqt.readthedocs.io/en/latest/), introducing snpQT using a synthetic demonstration dataset and a real-world Amyotrophic Lateral Sclerosis SNP-array dataset.}, } @article {pmid34941470, year = {2022}, author = {Ben-Porath, YS}, title = {A Comment on Krishnamurthy et al.'s (2022) Professional Practice Guidelines for Personality Assessment.}, journal = {Journal of personality assessment}, volume = {104}, number = {1}, pages = {17-18}, doi = {10.1080/00223891.2021.2006675}, pmid = {34941470}, issn = {1532-7752}, mesh = {Humans ; *Personality Assessment ; *Personality Disorders ; Professional Practice ; }, } @article {pmid34939510, year = {2022}, author = {Osman, SL and Lane, HL}, title = {Predicting College Women's Self-esteem Based on Verbal Coercion Experience and Verbal Tactic Items on the Revised Sexual Experiences Survey.}, journal = {Journal of interpersonal violence}, volume = {37}, number = {23-24}, pages = {NP23495-NP23503}, doi = {10.1177/08862605211062989}, pmid = {34939510}, issn = {1552-6518}, mesh = {Female ; Humans ; *Coercion ; Sexual Behavior ; Universities ; *Crime Victims ; Students ; }, abstract = {Verbal coercion experience is common among college women and has sometimes been associated with lower self-esteem. The current study examined self-esteem based on the two verbal coercion items included in the latest version of the most popular measure of sexual victimization experience, the Sexual Experiences Survey-Short Form Victimization (SES-SFV; Koss et al., 2007). One item includes verbal tactics categorized as "threat" and the other item includes verbal tactics categorized as "criticism." Undergraduate women (n = 479) completed the Rosenberg Self-Esteem Scale and the SES-SFV. Results showed that women who experienced criticism reported lower self-esteem than those who did not experience criticism. However, threat experience was not significantly related to women's self-esteem. Findings support Koss et al.'s suggestion that criticism tactics are more negative than threat tactics, and imply that self-esteem may be negatively associated with some sexually coercive verbal tactics but not associated with others. Future researchers should pay careful attention to operational definitions of verbal coercion.}, } @article {pmid34939115, year = {2022}, author = {Nelson, S and Agoston, M and Kovar-Gough, I and Cunningham, N}, title = {A Scoping Review and Proposed Framework for Coping in Youth With a History of Psychological Trauma and Chronic Pain.}, journal = {Journal of pediatric psychology}, volume = {47}, number = {4}, pages = {469-482}, pmid = {34939115}, issn = {1465-735X}, support = {K23 AT009458/AT/NCCIH NIH HHS/United States ; K23 AT010643/AT/NCCIH NIH HHS/United States ; K23AT009458//National Center for Complementary and Integrative Health-NCCIH/ ; }, mesh = {Adaptation, Psychological ; Adolescent ; Child ; *Chronic Pain ; Humans ; *Psychological Trauma ; *Stress Disorders, Post-Traumatic/diagnosis ; Surveys and Questionnaires ; }, abstract = {OBJECTIVE: Psychological trauma (e.g., abuse, neglect) and posttraumatic stress symptoms (PTSS) commonly occur in pediatric pain populations and may be related to various maladaptive coping strategies, which may in turn affect short- and long-term pain-related outcomes in youth. Accordingly, the current scoping review and conceptual framework seeks to identify important gaps in the field's current understanding of how coping impacts outcomes in youth who have experienced trauma/PTSS and pediatric chronic pain and explores avenues for future investigation.

METHODS: A scoping review of the literature was performed in Medline, Embase, Cochrane Library, PsycInfo, and Sociological Abstracts. Eligibility criteria included pediatric populations experiencing chronic pain, trauma, adverse childhood events, and/or PTSS and associated coping mechanisms. Nine research papers were selected and used to support the conceptual framework. The framework builds upon the work of Compas et al.'s' model of control-based coping (Compas et al., 2006; Compas & Harding Thomsen, 1999) and outlines the potential effects of trauma and/or PTSS and pain on coping and pain-related outcomes (e.g., pain chronicity, functional outcomes) in pediatric chronic pain populations.

RESULTS: A history of chronic pain and psychological trauma and/or PTSS in youth may contribute to increased risk for maladaptive coping and in turn, poorer pain-related and psychosocial outcomes long-term.

CONCLUSIONS: Findings from the current scoping review and proposed conceptual framework will guide future research and treatment efforts for youths experiencing pain and trauma and/or PTSS and thereby enhance long-term outcomes.}, } @article {pmid34936180, year = {2022}, author = {Clayton, A and Malone, WJ and Clarke, P and Mason, J and D'Angelo, R}, title = {Commentary: The Signal and the Noise-questioning the benefits of puberty blockers for youth with gender dysphoria-a commentary on Rew et al. (2021).}, journal = {Child and adolescent mental health}, volume = {27}, number = {3}, pages = {259-262}, doi = {10.1111/camh.12533}, pmid = {34936180}, issn = {1475-357X}, mesh = {Adolescent ; Adult ; *Gender Dysphoria/drug therapy ; Gender Identity ; Humans ; Puberty ; Sexual Behavior ; *Transgender Persons ; Male ; Female ; }, abstract = {This commentary is a critique of a recent systematic review of the evidence for the use of puberty blockers for youth with gender dysphoria (GD) by Rew et al. (2021). In our view, the review suffers from several methodological oversights including the omission of relevant studies and suboptimal analysis of the quality of the included studies. This has resulted in an incomplete and incorrect assessment of the evidence base for the use of puberty blockers. We find that Rew et al.'s conclusions and clinician recommendations are problematic, especially when discussing suicidality. A key message of the review's abstract appears to be that puberty blockers administered in childhood reduce adult suicidality. However, the study used for the basis of this conclusion (Turban et al., 2020) did not make a causal claim between puberty blockers and decreased adult suicidality. Rather, it reported a negative association between using puberty blockers and lifetime suicidal ideation. The study design did not allow for determination of causation. Our commentary concludes by demonstrating how the GD medical literature, as it moves from one publication to the next, can overstate the evidence underpinning clinical practice recommendations for youth with GD.}, } @article {pmid34931338, year = {2022}, author = {Gleibs, IH and Albayrak-Aydemir, N}, title = {Ethical concerns arising from recruiting workers from Amazon's Mechanical Turk as research participants: Commentary on Burnette et al. (2021).}, journal = {The International journal of eating disorders}, volume = {55}, number = {2}, pages = {276-277}, doi = {10.1002/eat.23658}, pmid = {34931338}, issn = {1098-108X}, mesh = {*Crowdsourcing/standards ; Data Collection/standards ; Humans ; }, abstract = {In this commentary, we respond to Burnette et al.'s (2021) paper, which gives significant practical recommendations to improve data quality and validity while gathering data via Amazon's Mechanical Turk (MTurk). We argue that it is also important to acknowledge and review the specific ethical issues that might arise when recruiting MTurk workers as participants. We particularly raise three main ethical concerns that need to be addressed when recruiting research participants from participant recruitment platforms: participants' economic vulnerability, participants' sensitivity, and power dynamics between participants and researchers. We elaborate on these issues by discussing the ways in which they may appear and be responded to. We conclude that considering the ethical aspects of data collection and the potential impacts of data collection on those involved would complement Burnette et al.'s recommendations. Consequently, data collection processes should be transparent as well, in addition to data screening processes.}, } @article {pmid34928693, year = {2022}, author = {Guimond, TH and Varma, S and Wnuk, SM and McMain, SF}, title = {A longitudinal approach to evaluating therapist and client contributions to alliance on outcomes in borderline personality disorder.}, journal = {Personality disorders}, volume = {13}, number = {6}, pages = {583-596}, doi = {10.1037/per0000526}, pmid = {34928693}, issn = {1949-2723}, support = {200204MCT-101123//CIHR/Canada ; }, mesh = {Humans ; *Borderline Personality Disorder/therapy/psychology ; Professional-Patient Relations ; Psychotherapy/methods ; }, abstract = {Methods for studying therapeutic alliance have primarily examined the impact of the early alliance on outcomes. This does not allow for an understanding of the contributions of client, therapist, and dyadic factors to the alliance. Also, the alliance may change over time, highlighting the need for longitudinal methods. Efforts have been made to develop approaches that decompose the contributing factors and their impact on outcomes, but these findings may not apply to clients with borderline personality disorder (BPD). Our study extends previous research by replicating Baldwin et al.'s (2007) approach to disentangling therapist versus client-therapist dyad effects while using a time-varying framework. Participants (n = 156) were individuals diagnosed with BPD randomized to 1 year of dialectical behavior therapy or general psychiatric management. Outcomes were general psychiatric severity and interpersonal functioning measured at baseline and every 4 months. Client-rated alliance was measured at these time points. Early alliance predicted interpersonal functioning (p = .0132) with a significant contribution from clients (p = .0248) but not therapists (p = .2854). In the time-varying analysis, client contribution to the alliance was significant (p = .0022). For general psychiatric severity, client contributions to the alliance were significant (p < .0001) but not therapist contributions (p = .6779). Client contribution to the alliance was significant (p = .0168) in the time-varying model. Results suggest that in a BPD sample, time-varying alliance is a better predictor of rate of change in outcomes compared with the alliance measured at a single time point. In contrast to other studies, client, not therapist, contributions to alliance were significant in predicting outcomes. (PsycInfo Database Record (c) 2022 APA, all rights reserved).}, } @article {pmid34928657, year = {2021}, author = {Ladd, GW and Troop-Gordon, W and Ettekal, I and Kochenderfer-Ladd, B}, title = {From social withdrawal to depression: A quasireplication and extension of Boivin, Hymel, and Bukowski (1995).}, journal = {Developmental psychology}, volume = {57}, number = {12}, pages = {2032-2049}, doi = {10.1037/dev0001162}, pmid = {34928657}, issn = {1939-0599}, mesh = {Child ; *Depression ; Female ; Humans ; *Loneliness ; }, abstract = {Tenets of the Boivin et al. (1995) social process model were reexamined with two longitudinal samples using both the original and contemporary analytic strategies. Study goals included reconstructing (e.g., quasireplicating) Boivin et al.'s (1995) original findings and evaluating hypothesized relations across both comparable and longer developmental epochs. Samples included 491 children (245 girls, Mage = 10.0; 80.1% White;19.1% low-, 43.1% middle- or higher-income) followed from grades 4 to 12 and 272 children (148 girls, Mage = 9.61; 84.2% White; 8.2% low-, 17.1% middle-, 74.7% upper middle to higher-income) followed from grades 4 to 5. The assumption that social withdrawal instigates a cascade of within-person changes in the quality of peer relationships, sense of loneliness and social dissatisfaction, and depression was evaluated using Boivin et al.'s (1995) original regression strategy plus two variants of cross-lagged panel models (classical CLPM; Latent Curve Model with Structured Residuals [LCM-SR]). Unlike classical CLPM, LCM-SR allowed for isolating within-person changes and testing hypothesized predictors of within-person increases and decreases. Results differed by type of analysis. Regression and classical CLPM yielded greater substantiation for some of the processes stipulated by Boivin et al. (1995). LCM-SR results, however, called into question the assumption of a cascade effect of early social withdrawal and the reliance on traditional regression and CLPM analyses to test for presumed predictors of within person change. (PsycInfo Database Record (c) 2021 APA, all rights reserved).}, } @article {pmid34927269, year = {2022}, author = {De Young, KP and Kambanis, PE}, title = {Practice makes perfect: Commentary on Burnette et al. (2021).}, journal = {The International journal of eating disorders}, volume = {55}, number = {2}, pages = {273-275}, doi = {10.1002/eat.23657}, pmid = {34927269}, issn = {1098-108X}, mesh = {Adult ; Cognition ; Data Collection/methods/standards ; *Feeding and Eating Disorders/diagnosis ; Humans ; Self Report ; }, abstract = {Underrepresented identities have been overlooked in the development of measures assessing eating disorders; therefore, limited normative data exist for these identities. To address this, Burnette et al. sought to provide Eating Disorder Examination-Questionnaire and Eating Attitudes Test-26 norms for transgender adults using Amazon's MTurk. However, they were unable to achieve this goal due to what they perceived as high rates of invalid responses. Instead, they provided recommendations for conducting MTurk research. However, little or no evidence supports the validity of several recommendations, partly because their study was not designed to derive or validate recommendations. By their own admission, their strategies failed to address what they identified as the central problem. We express concern about Burnette et al.'s recommendations because (a) the recommendations are built on assumptions about the problem that may not be true; and (b) the recommendations are not provided within the context of limitations of self-report/online data collection writ large. We detail these concerns and propose that strategies for mitigating inattentive/invalid responding be subjected to validation prior to being recommended to prevent the implementation of procedures that result in the exclusion of the target population, individuals who we historically, and perhaps still, unjustly exclude from research.}, } @article {pmid34923352, year = {2022}, author = {Ezumah, N and Manzano, A and Ezenwaka, U and Obi, U and Ensor, T and Etiaba, E and Onwujekwe, O and Ebenso, B and Uzochukwu, B and Huss, R and Mirzoev, T}, title = {Role of trust in sustaining provision and uptake of maternal and child healthcare: Evidence from a national programme in Nigeria.}, journal = {Social science & medicine (1982)}, volume = {293}, number = {}, pages = {114644}, pmid = {34923352}, issn = {1873-5347}, support = {MR/M01472X/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Child ; Child Health ; Female ; *Health Facilities ; Health Workforce ; Humans ; Nigeria ; Pregnancy ; *Trust ; }, abstract = {Despite increasing attention to implementation research in global health, evidence from low- and middle-income countries (LMICs) using realist evaluations, in understanding how complex health programmes work remains limited. This paper contributes to bridging this knowledge gap by reporting how, why and in what circumstances, the implementation and subsequent termination of a maternal and child health programme affected the trust of service users and healthcare providers in Nigeria. Key documents were reviewed, and initial programme theories of how context triggers mechanisms to produce intended and unintended outcomes were developed. These were tested, consolidated and refined through iterative cycles of data collection and analysis. Testing and validation of the trust theory utilized eight in-depth interviews with health workers, four focus group discussions with service users and a household survey of 713 pregnant women and analysed retroductively. The conceptual framework adopted Hurley's perspective on 'decision to trust' and Straten et al.'s framework on public trust and social capital theory. Incentives offered by the programme triggered confidence and satisfaction among service users, contributing to their trust in healthcare providers, increased service uptake, motivated healthcare providers to have a positive attitude to work, and facilitated their trust in the health system. Termination of the programme led to most service users' dissatisfaction, and distrust reflected in the reduction in utilization of MCH services, increased staff workloads leading to their decreased performance although residual trust remained. Understanding the role of trust in a programme's short and long-term outcomes can help policymakers and other key actors in the planning and implementation of sustainable and effective health programmes. We call for more theory-driven approaches such as realist evaluation to advance understanding of the implementation of health programmes in LMICs.}, } @article {pmid34914452, year = {2021}, author = {Lazarides, R and Dicke, AL and Rubach, C and Oppermann, E and Eccles, JS}, title = {Motivational profiles across domains and academic choices within Eccles et al.'s situated expectancy-value theoretical framework.}, journal = {Developmental psychology}, volume = {57}, number = {11}, pages = {1893-1909}, doi = {10.1037/dev0001250}, pmid = {34914452}, issn = {1939-0599}, support = {/MH/NIMH NIH HHS/United States ; //National Science Foundation/ ; //National Institute of Child Health and Human Development/ ; //NSF/ ; //Spencer Foundation/ ; //William T. Grant Foundation/ ; }, mesh = {Adolescent ; Adult ; Female ; Humans ; Male ; Michigan ; *Schools ; }, abstract = {This longitudinal person-centered study aimed to identify profiles of subjective task values and ability self-concepts of adolescents in the domain of mathematics, English, biology, and physics in Grades 10 and 12. We were interested in gendered changes of profile membership, and in relations between profile membership and educational and occupational outcomes in adulthood. Data were drawn from the Michigan Study of Adolescent and Adult Life Transitions. We focused on students who participated in the data collection in Grades 10 and 12 (N = 911; 56.1% female; Mage = 16.49, SD = .63; 91.2% European American, 4.6% African American, and 2.1% other ethnic groups such as Hispanic, Asian, Native American). Data on subsequent college majors were assessed 2, 6, and 10 years after finishing high school and data on occupational outcomes was assessed up to 22 years after high school. Using Latent Profile Analyses, our findings revealed five profiles in grade 10 and four profiles in grade 12, which were meaningfully related to student gender. Latent Transition Analyses showed that motivational beliefs became more hierarchical over time. Gendered changes in profile membership occurred, with boys experiencing a process of specialization into mathematics domains. We were also able to show that gender-specific intraindividual hierarchies of motivational beliefs were related to gender-specific specialization processes in adolescence and to subsequent gendered choices throughout the life course. (PsycInfo Database Record (c) 2021 APA, all rights reserved).}, } @article {pmid34914416, year = {2022}, author = {Gagnon, JC and Benedick, AR and Mason-Williams, L}, title = {Mental health interventions for youth who are incarcerated: A systematic review of literature.}, journal = {The American journal of orthopsychiatry}, volume = {92}, number = {4}, pages = {391-404}, doi = {10.1037/ort0000587}, pmid = {34914416}, issn = {1939-0025}, mesh = {Adolescent ; Correctional Facilities ; Humans ; *Mental Health ; *Prisoners ; }, abstract = {To promote the safety and well-being of youth who are incarcerated, the U.S. Departments of Justice and Education identified the importance of evidence-based mental health interventions. The purpose of this systematic review is to summarize and synthesize intervention research focusing on the mental health of youth who are incarcerated since the publication of Guiding Principles for Providing High-Quality Education in Juvenile Justice Secure Care Settings. ProQuest and Ebsco databases were searched to identify relevant published studies from 2015 to 2020. Eleven studies met the inclusion criteria. Studies mainly focused on cognitive-behavior interventions and included the following outcome domains: symptoms, functioning, personal growth, and multiple domains. To evaluate study quality, modified versions of Gersten et al.'s (2005) group design and Mulcahy et al.'s (2016) single-case design quality indicators were used. Of concern are the small number of studies, methodological limitations within studies, and lack of a common intervention and outcomes of focus that limit individual study conclusions and evaluation across studies. In particular, studies rarely included necessary information, such as participant mental health characteristics, interventionist training or qualifications, intervention details, and/or measures/reports of treatment integrity. For the Guiding Principles to be realized, one key issue is for government funding to target high-quality mental health interventions in juvenile correctional facilities within identified target areas. (PsycInfo Database Record (c) 2022 APA, all rights reserved).}, } @article {pmid34911656, year = {2022}, author = {Austin, EJ and Tsui, JI and Barry, MP and Tung, E and Glick, SN and Ninburg, M and Williams, EC}, title = {Health care-seeking experiences for people who inject drugs with hepatitis C: Qualitative explorations of stigma.}, journal = {Journal of substance abuse treatment}, volume = {137}, number = {}, pages = {108684}, pmid = {34911656}, issn = {1873-6483}, support = {R34 DA047660/DA/NIDA NIH HHS/United States ; }, mesh = {*Drug Users ; Female ; Hepacivirus ; *Hepatitis C ; Humans ; Male ; Patient Acceptance of Health Care ; Pharmaceutical Preparations ; Social Stigma ; *Substance Abuse, Intravenous ; }, abstract = {INTRODUCTION: People who inject drugs (PWID) have complex health needs and often experience poor health outcomes. For PWID, intersectional experiences of stigma and other social vulnerabilities may influence their experiences navigating medical care. We conducted a targeted subanalysis of qualitative interview data collected to inform development of a community-pharmacist care model for hepatitis C (HCV) among PWID to explore intersectional influences on health care-seeking experiences.

METHODS: The study recruited participants from community organizations in Seattle, Washington, and participants were eligible if they reported injection drug use within 3 months and having HCV. Study staff conducted semi-structured interviews and two independent coders transcribed and initially analyzed them using a Rapid Assessment Process, guided by the Consolidated Framework for Implementation Research. Themes emerged regarding intersections of stigma and social vulnerabilities; thus, we conducted a targeted subanalysis guided by Fundamental Cause Theory and Earnshaw et al.'s Stigma Framework.

RESULTS: Forty participants (65% male; 47% non-white) reported multiple social vulnerabilities (e.g., regarding unstable housing and food insecurity). Qualitative analysis identified that receiving health care in the context of social vulnerability is challenging and burdensome (Theme 1); health care interactions are fraught with stigma stemming from intersectional vulnerabilities (Theme 2); and the belief that abstaining from drug use is needed to prove worthiness for care (Theme 3). PWID described experiencing multiple social vulnerabilities (e.g., unmet basic needs) that made seeking health care burdensome. Interactions with health care teams further reinforced participants' feelings of shame about their drug use, which influenced how participants expressed their care preferences and felt heard by providers. And as PWID navigated health care, they felt that their status as an active drug user was used to control and sometimes coerce their access to services, discouraging PWID from seeking needed care.

CONCLUSIONS: Stigma and social vulnerabilities play a pervasive and intersecting role in the health care-seeking experiences of PWID and negatively impact their ability to navigate and receive care they need. Evidence-based stigma reduction interventions at multiple levels, coupled with person-centered approaches to care delivery, may help to mitigate negative impacts.}, } @article {pmid34901507, year = {2021}, author = {Alghazo, S and Al Salem, MN and Alrashdan, I and Rabab'ah, G}, title = {Grammatical devices of stance in written academic English.}, journal = {Heliyon}, volume = {7}, number = {11}, pages = {e08463}, doi = {10.1016/j.heliyon.2021.e08463}, pmid = {34901507}, issn = {2405-8440}, abstract = {Stance is a feature of academic writing that refers to how writers interact and engage with their readers by means of linguistic devices. This study focuses on the grammatical devices-and semantic distinctions thereof-that are employed by academic writers of English to express stance in research article abstracts in the areas of applied linguistics (AL) and literature (L). To this end, a corpus of 120 research article abstracts (60 in the area of AL and another 60 in that of L) was built and analysed using SPSS and following Biber et al.'s (1999) framework of grammatical devices of stance. The abstracts were extracted from high-quality journals in the respective areas: Applied Linguistics and English: Journal of the English Association. Both are ISI journals and published by Oxford Academic Publishing. A mixed-method approach, applying quantitative and qualitative measures, was adopted to answer the two questions: How is stance grammatically expressed in AL research article abstracts and L research article abstracts, and How is the expression of stance in AL research article abstracts similar to/different from that in L ones? The findings are construed in light of theories of academic discourse and English for Academic Purposes (EAP). The results reveal that there are important similarities and differences in the extent to which and the means through which stance is expressed in AL research article abstracts and L research article abstracts. In particular, the findings show that both AL and L abstracts were similar in the most frequently used stance marker which is the stance complement clause. However, they were different in the frequency of use of other devices. The study provides insights into the ways academic writers express stance in various fields which better our ability to write research article abstracts.}, } @article {pmid34900176, year = {2021}, author = {Chen, X and Zhang, X and Geng, D and Zhou, L and Chen, J and Lu, F}, title = {A RFID Authentication Protocol for Epidemic Prevention and Epidemic Emergency Management Systems.}, journal = {Journal of healthcare engineering}, volume = {2021}, number = {}, pages = {1550993}, pmid = {34900176}, issn = {2040-2309}, mesh = {*COVID-19 ; Humans ; Privacy ; *Radio Frequency Identification Device ; SARS-CoV-2 ; }, abstract = {The outbreak of the novel coronavirus has exposed many problems in the auxiliary information system for epidemic prevention and control, which needs to be resolved by using methods such as the antitampering of logistics data and the management and control of epidemic materials. This article discusses the introduction of emerging technologies such as Radio Frequency Identification (RFID), which support privacy protection into the auxiliary information system for epidemic prevention and control. Recently, this paper found that Khwaja et al.'s protocol (RAPUS protocol) is susceptible to database impersonation attacks and reader impersonation attacks. Therefore, this article proposes the enhanced protocol, which not only perfectly solves the problems of the abovementioned protocols but also comprehensively compares multiple protocols. The enhanced protocol has higher efficiency and security. The security of the proposed protocol (RAPUS + protocol) is analyzed by GNY logic and the AVISPA model. The designed scheme can help realize the safety and traceability of epidemic prevention materials and improve the automation and decision-making efficiency of the epidemic prevention.}, } @article {pmid34900022, year = {2021}, author = {Raveendran, A and Bazzul, J}, title = {Socialized medicine has always been political: COVID-19, science and biopower in India.}, journal = {Cultural studies of science education}, volume = {16}, number = {4}, pages = {995-1013}, pmid = {34900022}, issn = {1871-1502}, abstract = {In this article, we discuss the tensions surrounding science, biopower, and citizenship that have been thrown into sharp relief by the COVID 19 pandemic. We situate these tensions in the epistemological and political conflict between science, public health education, and alternative medical systems that has been rekindled by the pandemic in India. To do so, we critically examine media articles and health education documents in the form of illustrated narratives/posters to show how education, science, and biopower are inseparable; and must therefore be considered an important part of any programme of critical justice-oriented science education. We employ a biopolitical framework, drawing largely from the work of Michel Foucault, to expose relevant sociopolitical tensions between tradition and modernity, truth and power, governance and science, which are invoked in times of crisis (such as pandemics) and give shape to fundamentals issue of science and citizenship. This article attempts to add to the conversation begun by Flavia Rezende et al.'s (2021) "South Epistemologies to invent post-pandemic science education", who related the COVID-19 pandemic to the political situation in Brazil emphasizing the necessity to reclaim indigenous ways of being and relating to nature. We draw implications for science education research and praxis that exceed any one pandemic or political crisis.}, } @article {pmid34893725, year = {2021}, author = {Pausé, C and McAllister, TG and Simpson, AB and Graham, R and Calloway, L and Gillon, A and Halcrow, S and Jones, R and Keene, S and LaMarre, A and Parker, G and Powell, D and Santa Maria, T and Tohiariki, B and Tumilty, E and Vandewiele, C and Watkins, A and Withey-Rila, C}, title = {Teeth are for chewing: a critical review of the conceptualisation and ethics of a controversial intraoral weight-loss device.}, journal = {British dental journal}, volume = {231}, number = {11}, pages = {675-679}, doi = {10.1038/s41415-021-3680-x}, pmid = {34893725}, issn = {1476-5373}, mesh = {*Concept Formation ; Humans ; Male ; *Mastication ; }, abstract = {We are a diverse collective of researchers who are committed to improving the health and wellbeing of marginalised individuals. This article is a response to, and critique of, the DentalSlim Diet Control research. This device revises a controversial 1970s weight-loss technology connected to poor health outcomes, which is indicative of a culture that consistently promotes harm to fat and other marginalised communities.We address the historical context in which unruly bodies, particularly fat, and Indigenous bodies have been the site of unethical investigation conducted under the auspices of medical research. Existence outside the normative white, male, cis physical ideal demands regulation, and disciplinary measures. We demonstrate how Brunton et al.'s research is underpinned by anti-fat attitudes and assumptions which impose this punitive physical intervention onto healthy people in a way that should not be acceptable in medical research.Further, we address a range of harms, giving attention to Māori and to individuals with eating disorders, along with issues of research integrity. We argue that no ethics committee should have approved this research, no academic journal should have published it, and no member of the dental and medical community should promote or prescribe this device.}, } @article {pmid34883408, year = {2022}, author = {Holland, MR}, title = {More than chores: The invisible health work of family caregivers in rural New Brunswick, Canada.}, journal = {Health & place}, volume = {73}, number = {}, pages = {102726}, doi = {10.1016/j.healthplace.2021.102726}, pmid = {34883408}, issn = {1873-2054}, mesh = {Canada ; *Caregivers ; *Family ; Humans ; New Brunswick ; Rural Population ; }, abstract = {Most home care for people living with chronic illness or disability is provided by informal, or unpaid, family members. Family caregivers in rural New Brunswick engage in essential work to maintain the home as a site of care. Renovations, property maintenance, and the administrative work involved in accessing medical equipment and managing staff are examples of the types of invisible labour involved in interacting with a complex care environment. Conversations with 13 family caregivers across a small rural Canadian province suggest that even when resources are 'available', place-based factors involved in caring at home in a rural setting make it difficult for carers to use these resources and accessing them becomes another form of work itself. Similar to Wiles et al.'s (2018) findings in their study of end-of-life family care in Aotearoa, New Zealand, carers in rural New Brunswick spoke of their activities as part of an ongoing process of interaction with the care recipient and care environment. Carers with fewer financial and material resources experienced higher burdens of invisible work. The paper sheds light on the types of labour involved in 'knowing, doing, and negotiating' care at home and re-categorizes these activities as 'health work' as a means of informing home care policy. The paper finds that family caregivers are aware of their invisible work, characterize it as essential health work, and seek recognition for their complex contribution to the formal health system.}, } @article {pmid34882483, year = {2022}, author = {Bigler, RS and Pahlke, E and Williams, AD and Vittrup, B}, title = {White Parents' Socialization of Racial Attitudes: A Commentary on Scott et al. (2020).}, journal = {Perspectives on psychological science : a journal of the Association for Psychological Science}, volume = {17}, number = {3}, pages = {901-910}, doi = {10.1177/17456916211029947}, pmid = {34882483}, issn = {1745-6924}, mesh = {Attitude ; Child ; Humans ; Parenting/psychology ; Parents/psychology ; *Racism/psychology ; *Socialization ; }, abstract = {In the September 2020 issue of Perspectives, Scott et al. argued that there is insufficient empirical work on White parents' racial-socialization strategies to support generalizations about the topic and, therefore, that journalists' recommendation that White parents discuss race and racism with their children represents a case of speculation without evidence. Although we strongly support Scott et al.'s call for additional, rigorous research on racial socialization in White families, we argue that their critique of popular-press pieces was unwarranted. Specifically, we argue that, although definitive tests of the effects of specific White parental racial-socialization strategies are lacking, the recommendation for parents to discuss race and racism with their children is both appropriate and empirically grounded. We describe research on racial socialization, intergroup contact, and cognitive development that is consistent with recommendations from developmental scientists reported in the popular press. Furthermore, we argue that parents may be the ideal socializers of racial attitudes. We conclude with a discussion of the broad context concerning media reports of findings from psychological science.}, } @article {pmid34882036, year = {2022}, author = {Cheung, CK and Norlander, MG and Vest, AN and Thomas, BN and Zebrack, BJ}, title = {A Thin Line Between Helpful and Harmful Internet Usage: Embodied Research on Internet Experiences Among Adolescent and Young Adult Cancer Patients.}, journal = {Journal of adolescent and young adult oncology}, volume = {11}, number = {5}, pages = {478-485}, pmid = {34882036}, issn = {2156-535X}, support = {R25 CA186872/CA/NCI NIH HHS/United States ; }, mesh = {Young Adult ; Adolescent ; Humans ; Adult ; *Internet Use ; Health Promotion ; *Neoplasms ; Qualitative Research ; Internet ; }, abstract = {Purpose: The purpose of this study was to expand upon findings from a prior Delphi study of adolescent and young adults' (AYAs') preferences for cancer resources. Utilizing an embodied approach, this study intended to elucidate a deeper and nuanced understanding of the expressed benefits and risks of engaging in cancer-related online interactions. Methods: Using Gale et al.'s framework method for qualitative, multidisciplinary health research and Thanem and Knights's embodied research methods for the social sciences, an investigative team of embodied researchers (AYA cancer patients turned researchers) conducted semistructured in-depth interviews with AYA cancer patients (n = 10) diagnosed between ages 15 and 39 years. To generate themes, researchers identified commonalities and differences within the qualitative data, and indexed codes according to the agreed analytic framework. Furthermore, by fully engaging with personal reflexivity, bracketing, and analytic memos across data collection and analysis, the investigative team elucidated benefits and risks of embodied research. Results: Findings impart evidence on AYAs' needs for internet-based content at the time of cancer diagnosis, use of the internet to fulfill cancer-related needs, perception of gaps in online cancer resources, and advice to other AYA cancer patients accessing internet-based information and support. Content analysis of interview data on participants' descriptions of personal engagement with the internet revealed beneficial themes of empowerment and harmful themes of fear-inducing consequences. Conclusions: In our rapidly evolving context of postpandemic internet reliance, developers of online cancer content should prioritize and respond to the nuanced vulnerabilities of AYAs. Future research must include socioeconomically disadvantaged participants to better understand practical challenges and promote health equity.}, } @article {pmid34876323, year = {2022}, author = {Wintrup, J}, title = {Ethics, policy, and politics: A reply to Ashraf et al.}, journal = {Social science & medicine (1982)}, volume = {292}, number = {}, pages = {114624}, doi = {10.1016/j.socscimed.2021.114624}, pmid = {34876323}, issn = {1873-5347}, mesh = {*Global Health ; Humans ; Policy ; *Politics ; Poverty ; Zambia ; }, abstract = {In this reply to Ashraf et al.'s (2021) commentary, I defend my argument that the randomised control trial (RCT) conducted by Ashraf et al. has caused harm in Zambia. I engage with the central points made by Ashraf et al. (2021), but also discuss a broader issue that they chose not to address in their commentary: the politics and ethics of conducting RCTs in countries in the Global South and the political vision of economists who regard RCTs as a solution to poverty and global health problems.}, } @article {pmid34874003, year = {2021}, author = {Abrams, MJ and Tan, FH and Li, Y and Basinger, T and Heithe, ML and Sarma, A and Lee, IT and Condiotte, ZJ and Raffiee, M and Dabiri, JO and Gold, DA and Goentoro, L}, title = {A conserved strategy for inducing appendage regeneration in moon jellyfish, Drosophila, and mice.}, journal = {eLife}, volume = {10}, number = {}, pages = {}, pmid = {34874003}, issn = {2050-084X}, mesh = {Amputation, Surgical/*methods ; Animals ; Drosophila/*physiology ; Extremities/*physiology ; Hindlimb/*physiology ; Mice ; *Regeneration ; Scyphozoa/*physiology ; }, abstract = {Can limb regeneration be induced? Few have pursued this question, and an evolutionarily conserved strategy has yet to emerge. This study reports a strategy for inducing regenerative response in appendages, which works across three species that span the animal phylogeny. In Cnidaria, the frequency of appendage regeneration in the moon jellyfish Aurelia was increased by feeding with the amino acid L-leucine and the growth hormone insulin. In insects, the same strategy induced tibia regeneration in adult Drosophila. Finally, in mammals, L-leucine and sucrose administration induced digit regeneration in adult mice, including dramatically from mid-phalangeal amputation. The conserved effect of L-leucine and insulin/sugar suggests a key role for energetic parameters in regeneration induction. The simplicity by which nutrient supplementation can induce appendage regeneration provides a testable hypothesis across animals.}, } @article {pmid34872468, year = {2022}, author = {Shaw, J}, title = {Why Inconsistency Arguments Matter.}, journal = {The New bioethics : a multidisciplinary journal of biotechnology and the body}, volume = {28}, number = {1}, pages = {40-53}, doi = {10.1080/20502877.2021.2007643}, pmid = {34872468}, issn = {2050-2885}, mesh = {*Abortion, Induced ; *Abortion, Spontaneous ; Child ; Dissent and Disputes ; Female ; Humans ; Morals ; Pregnancy ; }, abstract = {Abortion opponents are sometimes accused of having inconsistent beliefs, actions, and/or priorities. If they were consistent, they would regard spontaneous abortions to be a greater moral tragedy, or they would adopt more frozen in vitro fertilization embryos, or they would support more robust social welfare programmes for children and single parents, or so on and so forth. Nicholas Colgrove, Bruce Blackshaw, and Daniel Rodger have recently argued that such inconsistency arguments 'fail en masse.' They propose three main objections: The Diversity Objection, The Other Beliefs Objection, and The Other Actions Objection. This paper argues that they are incorrect. First, Colgrove et al.'s objections rely on misrepresentations of inconsistency arguments, their structure and the extent to which their proponents have addressed counterarguments to them. Second, none of their objections show that these arguments fail as a whole.}, } @article {pmid34860623, year = {2022}, author = {Perry, SP and Skinner-Dorkenoo, AL and Abaied, JL and Waters, SF}, title = {Applying the Evidence We Have: Support for Having Race Conversations in White U.S. Families.}, journal = {Perspectives on psychological science : a journal of the Association for Psychological Science}, volume = {17}, number = {3}, pages = {895-900}, doi = {10.1177/17456916211029950}, pmid = {34860623}, issn = {1745-6924}, mesh = {Humans ; Parent-Child Relations ; Parenting/psychology ; Parents/psychology ; Race Relations ; *Racism/psychology ; Socialization ; }, abstract = {Popular press articles have advocated for parent-child conversations about race and racism to prevent children from developing racial biases, yet empirical investigations of the impact of racial socialization in White U.S. families are scarce. In an article published in Perspectives on Psychological Science in 2020, Scott et al. warned that, given the lack of empirical evidence, parents might actually do more harm than good by talking to their children about race. In this comment, we draw upon the literature on (a) racial socialization, (b) parenting and parent-child discourse, and (c) the role of nonverbal communication in parental socialization to inform our understanding of parents' ability to engage in race-related conversations in the absence of empirical guidance. We also highlight emerging evidence of the potential benefits of these conversations (even if parents are uncomfortable). In sum, the wealth of existing literature suggests that parents can successfully navigate challenging conversations with their children-which tends to result in better outcomes for children than avoiding those conversations. Thus, although we support Scott et al.'s call for researchers to develop more empirical research, we part with the authors' assertion that researchers need to wait for more sufficient evidence before providing recommendations to White parents-we believe that the time for White families to begin talking about race and racism is now.}, } @article {pmid34859360, year = {2022}, author = {Montgomery, K}, title = {Response-Corruption, Trust, and Professional Regulation.}, journal = {Journal of bioethical inquiry}, volume = {19}, number = {1}, pages = {129-134}, pmid = {34859360}, issn = {1872-4353}, mesh = {Humans ; Organizations ; Publishing ; *Scientific Misconduct ; *Trust ; }, abstract = {In their 2018 article in the Cambridge Quarterly of Healthcare Ethics, Little, Lipworth, and Kerridge unpack the concept of corruption and clarify the mechanisms that foster corruption and allow it to persist, noting that organizations are "corruptogenic." To address the "so-what" question, I draw on research about trust and trustworthiness, emphasizing that a person's well-being and sense of security require trust to be present at both the individual and organizational levels-which is not possible in an environment where corruption and misconduct prevail. I highlight similarities in Little et al.'s framing of corruption to the persistent problem of scientific misconduct in research and publishing. I acknowledge the challenges in stemming corruption in science and medicine and conclude with a discussion about the need to reinvigorate a web of stakeholders to actively engage in professional regulation.}, } @article {pmid34850996, year = {2022}, author = {Xu, H and Weetman, C and Hanusch, F and Inoue, S}, title = {Isolation of Cyclic Aluminium Polysulfides by Stepwise Sulfurization.}, journal = {Chemistry (Weinheim an der Bergstrasse, Germany)}, volume = {28}, number = {8}, pages = {e202104042}, pmid = {34850996}, issn = {1521-3765}, support = {ALLOWE 101001591//H2020 European Research Council/ ; }, abstract = {Despite the notable progress in aluminium chalcogenides, their sulfur congeners have rarely been isolated under mild conditions owing to limited synthetic precursors and methods. Herein, facile isolation of diverse molecular aluminium sulfides is achievable, by the reaction of N-heterocyclic carbene-stabilized terphenyl dihydridoaluminium (1) with various thiation reagents. Different to the known dihydridoaluminium 1[Tipp] , 1 features balanced stability and reactivity at the Al center. It is this balance that enables the first monomeric aluminium hydride hydrogensulfide 2, the six-membered cyclic aluminium polysulfide 4 and the five-membered cyclic aluminium polysulfide 6 to be isolated, by reaction with various equivalents of elemental sulfur. Moreover, a rare aluminium heterocyclic sulfide with Al-S-P five-membered ring (7) was obtained in a controlled manner. All new compounds were fully characterized by multinuclear NMR spectroscopy and elemental analysis. Their structures were confirmed by single-crystal X-ray diffraction studies.}, } @article {pmid34843318, year = {2022}, author = {Duan, C and Hill, CE and Jiang, G and Li, D and Li, Y and Zhang, S and Yan, Y and Yu, L and Lu, T}, title = {Meaning in life: Perspectives of experienced Chinese psychotherapists.}, journal = {Psychotherapy (Chicago, Ill.)}, volume = {59}, number = {1}, pages = {26-37}, doi = {10.1037/pst0000395}, pmid = {34843318}, issn = {1939-1536}, mesh = {China ; Humans ; *Professional-Patient Relations ; *Psychotherapists ; Psychotherapy ; Qualitative Research ; }, abstract = {We attempted a cross-cultural replication of Hill et al.'s (2017) consensual qualitative study of experienced Western therapists' perspectives on working with meaning in life (MIL) in psychotherapy. We thus interviewed 12 experienced Chinese therapists about their views on MIL, working with MIL in psychotherapy, and the meanings they derived from working as psychotherapists. Chinese participants typically defined MIL as involving freedom, responsibility, and valuing life and viewed MIL as underlying many clients' presenting concerns and thus playing a critical role in therapy. In terms of working with clients on MIL, therapists described specific intervention strategies (e.g., challenging clients to broaden their meaning) and related outcomes (e.g., enhanced motivation to change). They further indicated that for MIL work to be effective, therapists need to be competent for working with MIL and clients need to be aware of MIL issues and ready to work with them. Therapists also reported that they gained both personal and professional benefits from working with MIL in psychotherapy. A comparison with Hill et al. (2017) indicated some similarities (e.g., both viewed MIL as part of human existence and as underlying most client presenting concerns) and differences (e.g., Chinese therapists perceived MIL as involving a sense of responsibility to others whereas Western therapists did not mention this) between Chinese and Western therapists regarding MIL in psychotherapy. (PsycInfo Database Record (c) 2022 APA, all rights reserved).}, } @article {pmid34840531, year = {2022}, author = {Michalec, B and Hafferty, FW}, title = {Challenging the clinically-situated emotion-deficient version of empathy within medicine and medical education research.}, journal = {Social theory & health : STH}, volume = {20}, number = {3}, pages = {306-324}, pmid = {34840531}, issn = {1477-8211}, abstract = {In this paper, we argue that the notion of a clinically-situated empathy (e.g. physician empathy), is potentially problematic as it perpetuates an emotion-deficient version of empathy within medicine and medicine education research. Utilizing classic and contemporary empathy theory from various social science disciplines, we discuss how empathy in the general sense differs conceptually from clinically-situated empathy-paying particular attention to the role of emotional contagion. To highlight this contrast, we draw upon Hojat et al.'s model of physician empathy and how this body of work reflects broader medical-cultural norms that problematize the role and impact of emotions within the clinical encounter. Alternatively, we present a more encompassing model of empathy drawing upon the fields of social-psychology and social-neuroscience in order to bring the notion of "feeling with" and emotional contagion more specifically, into medical education, medical education research, and medicine more generally.}, } @article {pmid34824561, year = {2021}, author = {Lukey, A and Johnston, S and Montesanti, S and Donnelly, C and Wankah, P and Breton, M and Gaboury, I and Parniak, S and Pritchard, C and Berg, S and Maiwald, K and Mallinson, S and Green, LA and Oelke, ND}, title = {Facilitating Integration Through Team-Based Primary Healthcare: A Cross-Case Policy Analysis of Four Canadian Provinces.}, journal = {International journal of integrated care}, volume = {21}, number = {4}, pages = {12}, pmid = {34824561}, issn = {1568-4156}, abstract = {INTRODUCTION: Team-based care can improve integrated health services by increasing comprehensiveness and continuity of care in primary healthcare (PHC) settings. Collaborative models involving providers from different professions can help to achieve coordinated, high-quality person-centred care. In Canada, there has been variation in both the timing/pace of adoption and approach to interprofessional PHC (IPHC) policy. Provinces are at different stages in the development, implementation, and evaluation of team-based PHC models. This paper describes how different policies, contexts, and innovations across four Canadian provinces (British Columbia, Alberta, Ontario, Quebec) facilitate or limit integrated health services through IPHC teams.

METHODS: Systematic searches identified 100 policy documents across the four provinces. Analysis was informed by Walt and Gilson's Policy Triangle (2008) and Suter et al.'s (2009) health system integration principles. Provincial policy case studies were constructed and used to complete a cross-case comparison.

RESULTS: Each province implemented variations of an IPHC based model. Five key components were found that influenced IPHC and integrated health services: patient-centred care; team structures; information systems; financial management; and performance measurement.

CONCLUSION: Heterogeneity of the implementation of PHC teams across Canadian provinces provides an opportunity to learn and improve interprofessional care and integrated health services across jurisdictions.}, } @article {pmid34823133, year = {2021}, author = {Brupbacher, G and Gerger, H and Zander-Schellenberg, T and Straus, D and Porschke, H and Gerber, M and von Känel, R and Schmidt-Trucksäss, A}, title = {Reply to Hertenstein et al.'s commentary on Brupbacher et al.: The effects of exercise on sleep in unipolar depression: A systematic review and network meta-analysis.}, journal = {Sleep medicine reviews}, volume = {60}, number = {}, pages = {101562}, doi = {10.1016/j.smrv.2021.101562}, pmid = {34823133}, issn = {1532-2955}, mesh = {Humans ; *Depressive Disorder ; Exercise ; Network Meta-Analysis as Topic ; Sleep ; Systematic Reviews as Topic ; }, } @article {pmid34819898, year = {2021}, author = {Manini, G and Botta, F and Martín-Arévalo, E and Ferrari, V and Lupiáñez, J}, title = {Attentional Capture From Inside vs. Outside the Attentional Focus.}, journal = {Frontiers in psychology}, volume = {12}, number = {}, pages = {758747}, pmid = {34819898}, issn = {1664-1078}, abstract = {In this study, we jointly reported in an empirical and a theoretical way, for the first time, two main theories: Lavie's perceptual load theory and Gaspelin et al.'s attentional dwelling hypothesis. These theories explain in different ways the modulation of the perceptual load/task difficulty over attentional capture by irrelevant distractors and lead to the observation of the opposite results with similar manipulations. We hypothesized that these opposite results may critically depend on the distractor type used by the two experimental procedures (i.e., distractors inside vs. outside the attentional focus, which could be, respectively, considered as potentially relevant vs. completely irrelevant to the main task). Across a series of experiments, we compared both theories within the same paradigm by manipulating both the perceptual load/task difficulty and the distractor type. The results were strongly consistent, suggesting that the influence of task demands on attentional capture varies as a function of the distractor type: while the interference from (relevant) distractors presented inside the attentional focus was consistently higher for high vs. low load conditions, there was no modulation by (irrelevant) distractors presented outside the attentional focus. Moreover, we critically analyzed the theoretical conceptualization of interference using both theories, disentangling important outcomes for the dwelling hypothesis. Our results provide specific insights into new aspects of attentional capture, which can critically redefine these two predominant theories.}, } @article {pmid34817643, year = {2022}, author = {Copelli, F and Rovetti, J and Ammirante, P and Russo, FA}, title = {Human mirror neuron system responsivity to unimodal and multimodal presentations of action.}, journal = {Experimental brain research}, volume = {240}, number = {2}, pages = {537-548}, pmid = {34817643}, issn = {1432-1106}, mesh = {Electroencephalography/methods ; Humans ; *Mirror Neurons/physiology ; *Motor Cortex/physiology ; Movement/physiology ; }, abstract = {This study aims to clarify unresolved questions from two earlier studies by McGarry et al. Exp Brain Res 218(4): 527-538, 2012 and Kaplan and Iacoboni Cogn Process 8: 103-113, 2007 on human mirror neuron system (hMNS) responsivity to multimodal presentations of actions. These questions are: (1) whether the two frontal areas originally identified by Kaplan and Iacoboni (ventral premotor cortex [vPMC] and inferior frontal gyrus [IFG]) are both part of the hMNS (i.e., do they respond to execution as well as observation), (2) whether both areas yield effects of biologicalness (biological, control) and modality (audio, visual, audiovisual), and (3) whether the vPMC is preferentially responsive to multimodal input. To resolve these questions about the hMNS, we replicated and extended McGarry et al.'s electroencephalography (EEG) study, while incorporating advanced source localization methods. Participants were asked to execute movements (ripping paper) as well as observe those movements across the same three modalities (audio, visual, and audiovisual), all while 64-channel EEG data was recorded. Two frontal sources consistent with those identified in prior studies showed mu event-related desynchronization (mu-ERD) under execution and observation conditions. These sources also showed a greater response to biological movement than to control stimuli as well as a distinct visual advantage, with greater responsivity to visual and audiovisual compared to audio conditions. Exploratory analyses of mu-ERD in the vPMC under visual and audiovisual observation conditions suggests that the hMNS tracks the magnitude of visual movement over time.}, } @article {pmid34817138, year = {2021}, author = {Shapira, J and Norman, D}, title = {[ROBOTICS- WHY NOW?].}, journal = {Harefuah}, volume = {160}, number = {11}, pages = {727-728}, pmid = {34817138}, issn = {0017-7768}, mesh = {*Arthroplasty, Replacement, Knee ; Humans ; Knee Joint ; *Orthopedics ; *Robotics ; }, abstract = {Total knee arthroplasty is already one of the most successful procedures in orthopedics with high survival rates and excellent post-operative outcomes. Despite these satisfying results, robotic-guided arthroplasty is slowly but surely infiltrating both worldwide and domestic. In Steinfeld et al.'s review "Robotic Total Knee Arthroplasty" the authors navigate through the pros and cons of robotic-guided total knee arthroplasty and try to answer the question: Robotics, why now?}, } @article {pmid34814042, year = {2022}, author = {Kalenkovich, E and Shestakova, A and Kazanina, N}, title = {Frequency tagging of syntactic structure or lexical properties; a registered MEG study.}, journal = {Cortex; a journal devoted to the study of the nervous system and behavior}, volume = {146}, number = {}, pages = {24-38}, doi = {10.1016/j.cortex.2021.09.012}, pmid = {34814042}, issn = {1973-8102}, mesh = {Auditory Perception ; Comprehension ; Humans ; Language ; *Linguistics ; *Semantics ; }, abstract = {A traditional view on sentence comprehension holds that the listener parses linguistic input using hierarchical syntactic rules. Recently, physiological evidence for such a claim has been provided by Ding et al.'s (2016) MEG study that demonstrated, using a frequency-tagging paradigm, that regularly occurring syntactic constituents were spontaneously tracked by listeners. Even more recently, this study's results have been challenged as artifactual by Frank and Yang (2018) who successfully re-created Ding's results using a distributional semantic vector model that relied exclusively on lexical information and did not appeal to any hierarchical syntactic representations. The current MEG study was designed to dissociate the two interpretations of Ding et al.'s results. Taking advantage of the morphological richness of Russian, we constructed two types of sentences of different syntactic structure; critically, this was achieved by manipulating a single affix on one of the words while all other lexical roots and affixes in the sentence were kept the same. In Experiment 1, we successfully verified the intuition that due to almost complete lexical overlap the two types of sentences should yield the same activity pattern according to Frank and Yang's (2018) lexico-semantic model. In Experiment 2, we recorded Russian listeners' MEG activity while they listened to the two types of sentences. Contradicting the hierarchical syntactic account and consistent with the lexico-semantic one, we observed no difference across the conditions in the way participants tracked the stimuli properties. Corroborated by other recent evidence, our findings show that peaks interpreted by Ding et al. as reflecting higher-level syntactic constituency may stem from non-syntactic factors.}, } @article {pmid34810143, year = {2022}, author = {Miller, H and Bush, K and Delancy, M and Leo, N and Joshi, H and Saracco, B and Adams, A and Gaughan, J and Bonawitz, S}, title = {Effect of preoperative radiation on free flap outcomes for head and neck reconstruction: An updated systematic review and meta-analysis.}, journal = {Journal of plastic, reconstructive & aesthetic surgery : JPRAS}, volume = {75}, number = {2}, pages = {743-752}, doi = {10.1016/j.bjps.2021.09.050}, pmid = {34810143}, issn = {1878-0539}, mesh = {*Free Tissue Flaps ; *Head and Neck Neoplasms/complications/radiotherapy/surgery ; Humans ; Neck ; Postoperative Complications/epidemiology/etiology ; *Plastic Surgery Procedures/adverse effects/methods ; Retrospective Studies ; }, abstract = {BACKGROUND: There is an ongoing debate about whether neoadjuvant radiation therapy is associated with higher rates of postoperative complications after head and neck reconstruction. Herle et al. conducted a systematic review in 2014 of 24 studies, finding higher complication rates in irradiated fields. We sought to perform an exhaustive updated systematic review and meta-analysis.

METHODS: We conducted an updated systematic review of the literature, as outlined in our protocol, which was registered on PROSPERO. Databases included Medline, Embase, Cochrane Central, and Web of Science. There were no limits placed on the date range, place of publication, or origin. Exclusion criteria included patients less than 18 years of age, studies with less than 20 participants (n < 20), case studies, skull base reconstructions, and local tissue rearrangements. The combined results of the studies and relative risks (RR) were calculated.

RESULTS: 53 studies were included for analysis, including 5,086 free flaps in an irradiated field, and 9,110 free flaps in a non-irradiated field. Of the 53 studies, 21 studies overlapped with those discussed in Herle et al.'s study, with a total of 32 additional studies. Neoadjuvant radiation was found to be a statistically significant risk factor for postoperative complications (RR 1.579, P < 0.001), total flap failure (RR, 1.565; P < 0.001), and fistula (RR, 1.810; P < 0.001). Our work reaffirmed the findings of the Herle et al.

CONCLUSION: Preoperative radiation was associated with a statistically significant increase in the risk of total flap failure, fistula, and total complications but not partial flap failure. These high-morbidity complications must be taken into consideration when determining which patients should receive neoadjuvant radiation therapy.}, } @article {pmid34809673, year = {2021}, author = {Swan, LET}, title = {The impact of US policy on contraceptive access: a policy analysis.}, journal = {Reproductive health}, volume = {18}, number = {1}, pages = {235}, pmid = {34809673}, issn = {1742-4755}, mesh = {Contraception ; *Family Planning Policy ; Health Services Accessibility ; Humans ; *Patient Protection and Affordable Care Act ; Policy Making ; United States ; }, abstract = {BACKGROUND: Contraceptive access is influenced by policy decisions, which can expand and constrict the contraceptive options available. This study explored the impact of recent US federal policy on contraceptive access.

METHODS: Federal policy changes impacting contraceptive access over the past decade were identified in grey literature. These policy changes were organized into a timeline and analyzed according to Levesque et al.'s (2013) five dimensions of healthcare access (approachability, acceptability, availability/accommodation, affordability, and appropriateness), noting the most salient healthcare dimension impacted by the policy change and analyzing whether, according to this framework, the policy created a theoretical increase or decrease in contraceptive access.

RESULTS: Of those policy changes coded as increasing (n = 42) and decreasing (n = 28) contraceptive access, most were related to the affordability (increasing n = 13; decreasing n = 12), physical availability (increasing n = 10; decreasing n = 7), and appropriateness (increasing n = 12; decreasing n = 4) of contraceptive care. Policy changes largely followed partisan divides, with contraceptive access increasing in years with a Democratic president and decreasing when a Republican president was in office. Many policy changes were related to the Affordable Care Act (ACA) and Title X of the Public Health Services Act. The implementation of the ACA and subsequent updates to it have increased the affordability of contraception, whereas changes to Title X have decreased the availability and appropriateness of contraceptive care.

CONCLUSIONS: This study highlights recent policy changes impacting contraceptive access, organizing them according to the five dimensions of healthcare access. It outlines specific policy barriers to contraceptive access and provides suggestions for policy and practice action that will improve contraceptive access and reproductive autonomy. Opportunities to ensure contraceptive access for all Americans include promoting comprehensive sex education, extending the Community Health Center Fund, increasing contraceptive care options for people with employers who are exempted from the ACA contraceptive mandate, addressing discrimination and building trust in contraceptive care, and amplifying outreach efforts to combat misinformation and confusion created by continuous changes to key family planning policies. Continued research on the role of policy in determining reproductive autonomy is warranted, and practice and policy action is needed to improve contraceptive access.}, } @article {pmid34807670, year = {2023}, author = {Haaf, JM and Rouder, JN}, title = {Does every study? Implementing ordinal constraint in meta-analysis.}, journal = {Psychological methods}, volume = {28}, number = {2}, pages = {472-487}, doi = {10.1037/met0000428}, pmid = {34807670}, issn = {1939-1463}, abstract = {The most prominent goal when conducting a meta-analysis is to estimate the true effect size across a set of studies. This approach is problematic whenever the analyzed studies have qualitatively different results; that is, some studies show an effect in the predicted direction while others show no effect and still others show an effect in the opposite direction. In case of such qualitative differences, the average effect may be a product of different mechanisms, and therefore uninterpretable. The first question in any meta-analysis should therefore be whether all studies show an effect in the same, expected direction. To tackle this question a model with ordinal constraints is proposed where the ordinal constraint holds each study in the set. This "every study" model is compared with a set of alternative models, such as an unconstrained model that predicts effects in both directions. If the ordinal constraints hold, one underlying mechanism may suffice to explain the results from all studies, and this result could be supported by reduced between-study heterogeneity. A major implication is then that average effects become interpretable. We illustrate the model comparison approach using Carbajal et al.'s (2021) meta-analysis on the familiar-word-recognition effect, show how predictor analyses can be incorporated in the approach, and provide R-code for interested researchers. As common in meta-analysis, only surface statistics (such as effect size and sample size) are provided from each study, and the modeling approach can be adapted to suit these conditions. (PsycInfo Database Record (c) 2023 APA, all rights reserved).}, } @article {pmid34807660, year = {2021}, author = {Shipherd, JC and Lynch, K and Gatsby, E and Hinds, Z and DuVall, SL and Livingston, NA}, title = {Estimating prevalence of PTSD among veterans with minoritized sexual orientations using electronic health record data.}, journal = {Journal of consulting and clinical psychology}, volume = {89}, number = {10}, pages = {856-868}, doi = {10.1037/ccp0000691}, pmid = {34807660}, issn = {1939-2117}, mesh = {Female ; Humans ; Male ; Electronic Health Records ; Prevalence ; Sexual Behavior ; *Stress Disorders, Post-Traumatic/epidemiology ; United States/epidemiology ; United States Department of Veterans Affairs ; *Veterans ; Adolescent ; Young Adult ; Adult ; Middle Aged ; Aged ; Aged, 80 and over ; }, abstract = {Objective: Questionnaire studies show people with minoritized sexual orientations (MSOs) face increased risk for conditions including posttraumatic stress disorder (PTSD). This study replicated Harrington et al.'s (2019) electronic health record probabilistic algorithm to evaluate lifetime PTSD prevalence in Veterans Health Administration (VHA)-using veterans. Method: In 115,853 MSO veterans and a 1:3 matched (on sex assigned at birth, and age at and year of first VHA visit) sample of non-MSO veterans. Each veteran was given a probability of "likely PTSD" (0.0-1.0) and thresholds (e.g., 0.7) applied to minimize false positive classifications. Results: Veterans with MSO were 2.35 times, CI [2.33, 2.38], more likely to have "likely PTSD" than veterans with non-MSO. The prevalence of "likely PTSD" using the rule-based International Classification of Diseases (ICD) approach was 40.8% among the MSO group compared to 22.0% among the non-MSO group after excluding those with bipolar or schizophrenia diagnoses and those with limited VHA engagement. Without those exclusions, prevalence was slightly higher in both groups (46.1% vs. 24.3%, respectively; prevalence ratio: 1.90). Despite increased prevalence of exposure to military sexual trauma (MST; MSO = 20.7%; non-MSO = 8.3%) and double "likely PTSD" among MSO veterans, they were less likely to have a service-connected PTSD disability than their matched non-MSO (MSO = 78.1%; non-MSO = 87.6%) comparators. Conclusions: VHA-using veterans with MSO were twice as likely to have "likely PTSD" and exposure to MST than veterans with non-MSO. Veterans with MSO were less likely to be service connected for PTSD than non-MSO counterparts. (PsycInfo Database Record (c) 2021 APA, all rights reserved).}, } @article {pmid34807651, year = {2021}, author = {Mendenhall, T}, title = {We are in this together: Maintaining our health care teams' wellness during challenging times.}, journal = {Families, systems & health : the journal of collaborative family healthcare}, volume = {39}, number = {3}, pages = {541-543}, doi = {10.1037/fsh0000650}, pmid = {34807651}, issn = {1939-0602}, mesh = {*COVID-19 ; Child ; Communication ; Humans ; Pandemics ; Patient Care Team ; SARS-CoV-2 ; }, abstract = {Efforts to prevent or mitigate burnout in health care practice(s) are longstanding in both biomedical and mental health arenas-from early training in classrooms, internships, and residencies to postgraduate work in primary, secondary, tertiary, and other care contexts (Berg & Garrard, 1980; Chen et al., 2019; Prins et al., 2007). From generic advice about work/ life balance, sleep hygiene, physical activity, and healthy eating to specific interventions across individual and organizational levels designed to support trainees and providers who are personally decompensating and/or potentially putting their patients at risk, scientific and lay literature, resources, programming, and protocols are extant. Whether and how we-as individuals, care teams, and care systems-have advanced these efforts effectively are similarly diverse. COVID-19 changed this conversation-or at least the urgency of it. In some ways, this makes perfect sense in light of the increased hours that many of us suddenly found ourselves working (read: no more work/life balance). But there were a lot of other things-less expected things happened. In this issue, Cornelius et al.'s (2021) engagement with health care workers in New York City is illustrative. Unlike traversing something that is difficult but has a clear endpoint (like a 24-hr shift or a four-year residency), we do not know when this pandemic will be over. It feels like running a marathon with no mile markers or celebratory finish line. And unlike offering responsive care to a specific community in a defined geographic area (like one impacted by a terrorist attack or a hurricane), we do not know where this pandemic's virus is. Because we cannot actually see COVID-19, we worry more about catching it. If we catch it, we might bring it home. If we bring it home, we could kill our spouses. Or our children. Maybe our whole families. It is hard to do good work when we carry emotional burdens like that. (PsycInfo Database Record (c) 2021 APA, all rights reserved).}, } @article {pmid34806394, year = {2022}, author = {Lin, X and Chen, P and Lin, F}, title = {Mapping global research trends in diabetes and COVID-19 outbreak in the past year: a bibliometric analysis.}, journal = {Annals of palliative medicine}, volume = {11}, number = {4}, pages = {1241-1252}, doi = {10.21037/apm-21-2636}, pmid = {34806394}, issn = {2224-5839}, mesh = {Bibliometrics ; *COVID-19/epidemiology ; Cytokine Release Syndrome ; *Diabetes Mellitus/epidemiology ; Disease Outbreaks ; Humans ; *Hyperglycemia ; SARS-CoV-2 ; United States ; }, abstract = {BACKGROUND: Diabetes is an independent risk factor for COVID-19 patients, and SARS-CoV-2 infection may in turn induce hyperglycemia. In this work, we will map the trends of global research of COVID-19 and diabetes by using the method of bibliometric analysis, help researchers quickly understand the research hotspots and find meaningful research directions.

METHODS: Documents related to COVID-19 and diabetes were obtained from the database of Science Citation Index Expanded of Web of Science. We then analysed the data by country/organization coauthorship analysis, sources/documents citation analysis, and keywords co-occurrence analysis. VOSviewer was applied to map the global research trends and hotspots in this field.

RESULTS: A total of 1,206 articles were retrieved, including a total of 101 countries, 2,595 organizations, 526 journals, and 3,405 keywords. China had the highest total citations, followed by the United States, while these two countries were reversed in terms of the number of documents. Half of the top 10 highly cited organizations were from China, including Capital Medical University, which had the highest citations, and Huazhong University of Science and Technology, which had the largest number of documents. Diabetes Research and Clinical Practice was the most productive journal. Journal of Medical Virology was the most highly cited journal. Zhou et al.'s article (The Lancet, 2020) was the most representative and widely cited. The keywords mainly focused on 3 categories, namely risk factors & clinical outcomes, receptor ACE2 & cytokine storm, as well as clinical characteristics & epidemiology. Among them, hyperglycemia, obesity, outcomes, and cytokine storm are the hotspots of recent concern.

CONCLUSIONS: This research mapped the global research trends in COVID-19 and diabetes, which may help researchers identify relevant collaborators and discover current hotspots and potential research directions.}, } @article {pmid34806026, year = {2021}, author = {Sun, H and Zhou, W and Kang, J}, title = {A review of crack growth models for near-neutral pH stress corrosion cracking on oil and gas pipelines.}, journal = {Journal of infrastructure preservation and resilience}, volume = {2}, number = {1}, pages = {28}, pmid = {34806026}, issn = {2662-2521}, abstract = {This paper presents a review of four existing growth models for near-neutral pH stress corrosion cracking (NNpHSCC) defects on buried oil and gas pipelines: Chen et al.'s model, two models developed at the Southwest Research Institute (SwRI) and Xing et al.'s model. All four models consider corrosion fatigue enhanced by hydrogen embrittlement as the main growth mechanism for NNpHSCC. The predictive accuracy of these growth models is investigated based on 39 crack growth rates obtained from full-scale tests conducted at the CanmetMATERIALS of Natural Resources Canada of pipe specimens that are in contact with NNpH soils and subjected to cyclic internal pressures. The comparison of the observed and predicted crack growth rates indicates that the hydrogen-enhanced decohesion (HEDE) component of Xing et al.'s model leads to on average reasonably accurate predictions with the corresponding mean and coefficient of variation (COV) of the observed-to-predicted ratios being 1.06 and 61.2%, respectively. The predictive accuracy of the other three models are markedly poorer. The analysis results suggest that further research is needed to improve existing growth models or develop new growth models to facilitate the pipeline integrity management practice with respect to NNpHSCC.}, } @article {pmid34798721, year = {2022}, author = {Shah, S and Gwee, SXW and Ng, JQX and Lau, N and Koh, J and Pang, J}, title = {Wastewater surveillance to infer COVID-19 transmission: A systematic review.}, journal = {The Science of the total environment}, volume = {804}, number = {}, pages = {150060}, pmid = {34798721}, issn = {1879-1026}, mesh = {*COVID-19 ; Humans ; Public Health ; SARS-CoV-2 ; Wastewater ; *Wastewater-Based Epidemiological Monitoring ; }, abstract = {Successful detection of SARS-COV-2 in wastewater suggests the potential utility of wastewater-based epidemiology (WBE) for COVID-19 community surveillance. This systematic review aims to assess the performance of wastewater surveillance as early warning system of COVID-19 community transmission. A systematic search was conducted in PubMed, Medline, Embase and the WBE Consortium Registry according to PRISMA guidelines for relevant articles published until 31st July 2021. Relevant data were extracted and summarized. Quality of each paper was assessed using an assessment tool adapted from Bilotta et al.'s tool for environmental science. Of 763 studies identified, 92 studies distributed across 34 countries were shortlisted for qualitative synthesis. A total of 26,197 samples were collected between January 2020 and May 2021 from various locations serving population ranging from 321 to 11,400,000 inhabitants. Overall sample positivity was moderate at 29.2% in all examined settings with the spike (S) gene having maximum rate of positive detections and nucleocapsid (N) gene being the most targeted. Wastewater signals preceded confirmed cases by up to 63 days, with 13 studies reporting sample positivity before the first cases were detected in the community. At least 50 studies reported an association of viral load with community cases. While wastewater surveillance cannot replace large-scale diagnostic testing, it can complement clinical surveillance by providing early signs of potential transmission for more active public health responses. However, more studies using standardized and validated methods are required along with risk analysis and modelling to understand the dynamics of viral outbreaks.}, } @article {pmid34796817, year = {2021}, author = {Kampis, D and Csibra, G}, title = {Three cognitive mechanisms for knowledge tracking.}, journal = {The Behavioral and brain sciences}, volume = {44}, number = {}, pages = {e157}, doi = {10.1017/S0140525X20001843}, pmid = {34796817}, issn = {1469-1825}, mesh = {*Cognition ; Humans ; }, abstract = {We welcome Phillips et al.'s proposal to separate the understanding of "knowledge" from that of "beliefs." We argue that this distinction is best specified at the level of the cognitive mechanisms. Three distinct mechanisms are discussed: tagging one's own representations with those who share the same reality; representing others' representations (metarepresenting knowledge); and attributing dispositions to provide useful information.}, } @article {pmid34796813, year = {2021}, author = {Moss, J}, title = {Knowledge before belief in the history of philosophy.}, journal = {The Behavioral and brain sciences}, volume = {44}, number = {}, pages = {e162}, doi = {10.1017/S0140525X20001612}, pmid = {34796813}, issn = {1469-1825}, mesh = {Humans ; *Knowledge ; *Philosophy ; }, abstract = {I add support to Phillips et al.'s thesis that representations of knowledge are more basic than representations of belief through a historical account of the development of philosophical theories of knowledge and belief. On the basis of Aristotle's criticisms of his Presocratic predecessors, I argue that Western philosophy developed theories of knowledge long before it developed theories of belief.}, } @article {pmid34796800, year = {2021}, author = {Kano, F and Call, J}, title = {Evolutionary foundations of knowledge and belief attribution in nonhuman primates.}, journal = {The Behavioral and brain sciences}, volume = {44}, number = {}, pages = {e158}, doi = {10.1017/S0140525X20001521}, pmid = {34796800}, issn = {1469-1825}, mesh = {Animals ; *Hominidae ; Knowledge ; Social Perception ; *Theory of Mind ; }, abstract = {Recent findings from anticipatory-looking false-belief tests have shown that nonhuman great apes and macaques anticipate that an agent will go to the location where the agent falsely believed an object to be. Phillips et al.'s claim that nonhuman primates attribute knowledge but not belief should thus be reconsidered. We propose that both knowledge and belief attributions are evolutionary old.}, } @article {pmid34796796, year = {2021}, author = {Farina, M and Lavazza, A}, title = {Knowledge prior to belief: Is extended better than enacted?.}, journal = {The Behavioral and brain sciences}, volume = {44}, number = {}, pages = {e152}, doi = {10.1017/S0140525X2000076X}, pmid = {34796796}, issn = {1469-1825}, mesh = {*Cognition ; Humans ; *Knowledge ; }, abstract = {In this commentary, we argue that Phillips et al.'s findings can be used to provide new important insights in the debate between externalists' theories of cognition. In particular, we claim that the results presented in this target article may offer us the conceptual palette needed for a sustained defence of an extended account of cognition over an enactive one.}, } @article {pmid34793248, year = {2022}, author = {Giangrande, EJ and Turkheimer, E}, title = {Race, Ethnicity, and the Scarr-Rowe Hypothesis: A Cautionary Example of Fringe Science Entering the Mainstream.}, journal = {Perspectives on psychological science : a journal of the Association for Psychological Science}, volume = {17}, number = {3}, pages = {696-710}, doi = {10.1177/17456916211017498}, pmid = {34793248}, issn = {1745-6924}, support = {R01 AG063949/AG/NIA NIH HHS/United States ; R03 AG048850/AG/NIA NIH HHS/United States ; }, mesh = {*Ethnicity ; Humans ; Intelligence/genetics ; *Social Class ; United States ; }, abstract = {In 2020, Pesta et al. published an article entitled "Racial and Ethnic Group Differences in the Heritability of Intelligence: A Systematic Review and Meta-Analysis" in the journal Intelligence. The authors framed their analysis as an examination of the Scarr-Rowe hypothesis, which holds that the heritability of intelligence varies as a function of socioeconomic status. Pesta et al. concluded that the heritability of intelligence does not differ across racial and ethnic groups in the United States. They claimed their results challenge the Scarr-Rowe hypothesis and support the hereditarian position that mean differences in IQ among racial and ethnic groups are attributable to genetic differences rather than environmental disparities. In this commentary, we outline severe theoretical, methodological, and rhetorical flaws in every step of Pesta et al.'s meta-analysis. The most reliable finding from Pesta et al. is consistent with the Scarr-Rowe hypothesis and directly contradicts a hereditarian understanding of group differences in intelligence. Finally, we suggest that Pesta et al. serves as an example of how racially motivated and poorly executed work can find its way into a mainstream scientific journal, underscoring the importance of robust peer review and rigorous editorial judgment in the open-science era.}, } @article {pmid34784992, year = {2023}, author = {Sariaslan, A and Fazel, S}, title = {Reply to Seon et al.'s 'To prevent arrest and convictions, prescribe antipsychotics'.}, journal = {Psychological medicine}, volume = {53}, number = {7}, pages = {3236-3237}, doi = {10.1017/S0033291721004530}, pmid = {34784992}, issn = {1469-8978}, support = {202836/Z/16/Z/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Humans ; *Antipsychotic Agents ; Law Enforcement ; }, } @article {pmid34784982, year = {2021}, author = {Lamba, G and Shroff, ZC and Babar, ZU and Ghaffar, A}, title = {Drug shops for stronger health systems: learning from initiatives in six LMICs.}, journal = {Journal of pharmaceutical policy and practice}, volume = {14}, number = {Suppl 1}, pages = {94}, pmid = {34784982}, issn = {2052-3211}, support = {001/WHO_/World Health Organization/International ; }, abstract = {BACKGROUND: Private sector retail pharmacies, or drug shops, play an important role in access to essential medicines and services in low-and-middle-income countries. Recognising that they have the potential to contribute to health system strengthening efforts, many recent initiatives to engage with drug shops have been launched. These include initiatives that focus on changes in policy, regulation and training. However, the specific factors that influence their success remain poorly understood. Seven country case studies supported under the Alliance's programme of work 'Strengthening health systems: the role of drug shops' help to explore this issue.

METHODS: Country case studies from the above programme of research from Bangladesh, Indonesia, Myanmar, Nigeria, Tanzania and Zambia were used as the main sources of data for this paper. A modified version of Bigdeli et al.'s Access to Medicines framework was applied within a partially grounded approach to analyze each country case study and compare themes between countries.

RESULTS: Many factors may help initiatives targeting drug shops successfully achieve their intended outcomes. At the micro level, these include community demand for drug shops and a positive relationship between drug shops and their clients. At the meso level, facilitators of initiative success include training and positive attitudes from drug shops towards the initiative. Barriers include client pressure, procurement challenges and financial and administrative costs associated with initiatives. At the macro level, collaboration between stakeholders, high-level buy in and supervision, monitoring and regulation may influence initiative success. These factors are inter-dependent and interact with each other in a dynamic way.

CONCLUSIONS: Using a framework approach, these country case studies demonstrate common factors that influence how drug shops can strengthen health systems. These learnings can help inform the design and implementation of successful strategies to engage drug shops towards sustainable systems change.}, } @article {pmid34784502, year = {2021}, author = {Frank, JW and Marion, G and Doeschl-Wilson, A}, title = {Development of a critical appraisal tool for models predicting the impact of 'test, trace, and protect' programmes on COVID-19 transmission.}, journal = {Public health}, volume = {201}, number = {}, pages = {55-60}, pmid = {34784502}, issn = {1476-5616}, mesh = {*COVID-19 ; Humans ; Pandemics ; Public Health ; SARS-CoV-2 ; }, abstract = {OBJECTIVES: To develop a critical appraisal tool for non-computational-specialist public health professionals to assess the quality and relevance of modelling studies about Test and Trace (and Protect - TTP) programmes' impact on COVID-19 transmission.

STUDY DESIGN: Decision-making tool development.

METHODS: Using Tugwell et al.'s 1985 Health Care Effectiveness equation as a conceptual framework, combined with a purposive search of the relevant early modeling literature, we developed six critical appraisal questions for the rapid assessment of modeling studies related to the evaluation of TTP programmes' effectiveness.

RESULTS: By applying the critical appraisal tool to selected recent COVID-19 modeling studies, we demonstrate how models can be evaluated using the six questions to evaluate internal and external validity and relevance.

CONCLUSIONS: These six critical appraisal questions are able to discriminate between modeling studies of higher and lower quality and relevance to evaluating TTP programmes' impact. However, these questions require independent validation in a larger and systematic sample of relevant modeling studies which have appeared in later stages of the pandemic.}, } @article {pmid34780216, year = {2021}, author = {Webster, GD and Mahar, EA and Wongsomboon, V}, title = {American psychology is becoming more international, but too slowly: Comment on Thalmayer et al. (2020).}, journal = {The American psychologist}, volume = {76}, number = {5}, pages = {802-805}, doi = {10.1037/amp0000747}, pmid = {34780216}, issn = {1935-990X}, mesh = {*Societies, Scientific ; United States ; }, abstract = {Commenting on Thalmayer, Toscanelli, and Arnett (2020), we provide broader analysis of the national institutional affiliations of authors (2,978), editors (286), and consulting editors (2,652) from seven (vs. six) American Psychological Association (APA) journals that span over 40 (vs. 30) years. Using multilevel models, results showed that percentages of lead authors at American institutions decreased linearly and significantly and over time. Predicted mean percentages of American authors were 86% in 1978 versus 54% in 2018, a decrease of 37%. Percentages of editors and consulting editors at American institutions also decreased significantly; however, the effect for consulting editors was also quadratic-the linear decline accelerated over time. Predicted mean percentages of American consulting editors at 10-year intervals (1980-2020) were 94%, 92%, 89%, 80%, and 69%. Our 2020 predicted mean of 69% American consulting editors was notably lower than Thalmayer et al.'s (2020) 2018 mean of 82%. In addition, higher-impact journals had more pronounced quadratic declines in the percentages of American consulting editors over time. American psychology continues to become more international, but not quickly enough. We concur with Thalmayer et al.'s (2020) policy proposals, especially that APA journals and their editors should actively pursue non-American associate and consulting editors. (PsycInfo Database Record (c) 2021 APA, all rights reserved).}, } @article {pmid34758645, year = {2021}, author = {Wilson, YP and Nambiar, P and Yaacob, H and Asif, MK}, title = {Age estimation from developing third molars.}, journal = {The Medico-legal journal}, volume = {89}, number = {4}, pages = {254-259}, doi = {10.1177/00258172211052930}, pmid = {34758645}, issn = {2042-1834}, mesh = {Adolescent ; *Age Determination by Teeth ; Child ; Female ; Humans ; Male ; Mandible/diagnostic imaging ; *Molar, Third/diagnostic imaging ; Radiography, Panoramic ; }, abstract = {We investigated the development of third molars among Malaysians (including variations between jaws and genders) using Demirjian's method. Dental panoramic radiographs of 1224 subjects aged 8 to 24 years were examined, and the molars were assigned Demirjian et al.'s development grades (A-H). Results indicated that 18.8% had congenitally missing or extracted third molars. Development of molars begins earlier in females (also in the mandible), but by age 9, male children's molar development speeds up with more advanced grades in their middle teens than females. Grade C indicates the subject is a juvenile, while initiation of root development (Grade E), was observed from 13 years on. Grade H can occur in a child aged 18 years who technically is still a juvenile. We compared the development and growth patterns of the third molar from both the maxilla and the mandible.}, } @article {pmid34750773, year = {2022}, author = {Levaque, E and Dawson, SJ and Wan, C and Lalumière, ML}, title = {Sex Drive as a Possible Mediator of the Gender Difference in the Prevalence of Paraphilic Interests in a Nonclinical Sample.}, journal = {Archives of sexual behavior}, volume = {51}, number = {2}, pages = {867-877}, pmid = {34750773}, issn = {1573-2800}, mesh = {Female ; Humans ; Libido ; Male ; *Paraphilic Disorders/epidemiology ; Prevalence ; Sex Factors ; Sexual Behavior ; }, abstract = {There is a general gender difference in paraphilic interests, such that men report more interest (and greater engagement) in a variety of paraphilic behaviors. Using a nonclinical sample, Dawson et al. (Sexual Abuse, 28(1):20-45, 2016, https://doi.org/10.1177/1079063214525645) found that the gender difference in paraphilic interests was eliminated when scores on measures of sex drive were used as mediators. However, their measures of sex drive were about more than just sex drive and included a measure of hypersexuality (i.e., distress, perceived lack of control, and problematic consequences of one's sexuality). This study had two aims: to replicate Dawson et al.'s mediation results (using the same measures and scoring methods), and to discern the effect of sex drive itself (by replacing their measure of hypersexuality with a measure of sex drive). A nonclinical sample of 517 men and 615 women completed an online questionnaire. As expected, men reported less repulsion than women for most paraphilic themes. The gender difference in paraphilic interests was reduced (but not eliminated) both when reproducing Dawson et al.'s analysis and when examining a mediation model focused on sex drive specifically. The same results were obtained when examining the paraphilic interest with the largest gender difference (i.e., voyeurism). A full mediation effect was obtained in an unplanned supplementary analysis using a factor score (derived from eight measures) putatively assessing sex drive. While the main findings are consistent with Dawson et al.'s conclusions that sex drive is a possible mediator, they also suggest that other factors need to be considered to help explain the gender difference in the prevalence of paraphilic interests.}, } @article {pmid34748710, year = {2022}, author = {Smith, GC}, title = {Why is formulation daunting? A response to Bagster et al.'s 'instructions' for developing skills in formulation.}, journal = {Australasian psychiatry : bulletin of Royal Australian and New Zealand College of Psychiatrists}, volume = {30}, number = {2}, pages = {266-268}, doi = {10.1177/10398562211054038}, pmid = {34748710}, issn = {1440-1665}, mesh = {Humans ; *Mental Disorders/diagnosis ; }, abstract = {OBJECTIVE: To explore the theme identified by Bagster et al.[1] in their selective psychiatric literature review that formulation can appear daunting.

CONCLUSION: Formulation is understandably daunting, even though it occurs in all human encounters. The plural nature of mental symptoms is such that anxiety-provoking intuitive judgement is required at all points in both the process and explication of formulation, a type of instinctive guessing. There are no rules for this, because the laws of vertical integration of systems are not established. Guidelines are more appropriate than 'instructions'. Much of the wider mental health and clinical reasoning literature addresses intuitive judgement, but the current psychiatric literature tends to focus on pattern recognition as a deliberative cognitive act of Type 2 processes. Arguably this reductionism adds to the dauntingness. Anxiety detected about the intuitive judgement involved can be addressed in supervision, taking into account the psychological mindedness of the trainee.}, } @article {pmid34745382, year = {2021}, author = {Zuk, P and Lázaro-Muñoz, G}, title = {DBS and Autonomy: Clarifying the Role of Theoretical Neuroethics.}, journal = {Neuroethics}, volume = {14}, number = {Suppl 1}, pages = {83-93}, pmid = {34745382}, issn = {1874-5490}, support = {R01 MH114854/MH/NIMH NIH HHS/United States ; }, abstract = {Gilbert, Viaña, and Ineichen call for further empirical work on the effects of deep brain stimulation (DBS) on personality, identity, agency, authenticity, autonomy and self (PIAAAS) (Gilbert et al. 2018a). In particular, they emphasize the need for more sophisticated instruments measuring potential changes in PIAAAS. The development of such instruments, they argue, will provide a stronger empirical foundation for theoretical neuroethics work on DBS. We agree with this proposal. However, we believe that theoretical neuroethics has an important role to play in advancing empirical neuroethics that is not emphasized in Gilbert et al.'s remarks on the relationship between empirical and theoretical neuroethics. The development of instruments for more fully assessing changes in PIAAAS will require significant clarification of its component concepts. This task of clarification is the purview of theoretical neuroethics. In this article, we sketch how theoretical neuroethics can clarify the concept of autonomy. We hope that this can both serve as a model for the conceptual clarification of other components of PIAAAS and contribute to the development of the empirical measures that Gilbert and colleagues propose.}, } @article {pmid34740503, year = {2022}, author = {Saad, S and Osman, NI and Chapple, CR}, title = {Reply to Sanjay B. Kulkarni, Pankaj M. Joshi, Marco Bandini, et al.'s Letter to the Editor re: Sanad Saad, Nadir I. Osman, Christopher R. Chapple. Female Urethra: Is Ventral the True Dorsal? Eur Urol 2020;78:e218-9.}, journal = {European urology}, volume = {81}, number = {1}, pages = {e16-e17}, doi = {10.1016/j.eururo.2021.09.032}, pmid = {34740503}, issn = {1873-7560}, mesh = {Female ; Humans ; *Multiparametric Magnetic Resonance Imaging ; Urethra ; *Urinary Bladder Neoplasms ; }, } @article {pmid34735177, year = {2023}, author = {Sackett, PR and Zhang, C and Berry, CM}, title = {Challenging conclusions about predictive bias against Hispanic test takers in personnel selection.}, journal = {The Journal of applied psychology}, volume = {108}, number = {2}, pages = {341-349}, doi = {10.1037/apl0000978}, pmid = {34735177}, issn = {1939-1854}, mesh = {Humans ; *Personnel Selection ; Aptitude Tests ; Hispanic or Latino ; *Work Performance ; Research Design ; }, abstract = {Berry et al. (2020) noted that predictive bias is a function of three factors: subgroup mean difference on the predictor (dx), subgroup mean difference on the criterion (dy), and test validity (rxy). They used meta-analytic estimates of each of these three to examine predictive bias against Hispanic test takers when cognitive tests are used in personnel selection. They found that tests underpredict Hispanic job performance by an average of .21 SDs, which would call into question the fairness of cognitive test use in personnel selection. We located 119 studies in which all three parameters-dy, dx, and rxy-could be obtained, thus holding sample, setting, and operationalization constant in estimating the three parameters within each study. This produced a substantially different conclusion: We find that tests overpredict Hispanic performance by .04-.20 SDs, depending on assumptions made about artifact corrections. Factors contributing to differences between the two studies include differences in range restriction corrections, sample incomparability, and Berry et al.'s use of rxy estimated from the total sample rather than within the majority subgroup. (PsycInfo Database Record (c) 2023 APA, all rights reserved).}, } @article {pmid34734804, year = {2021}, author = {Quidwai, T and Wang, J and Hall, EA and Petriman, NA and Leng, W and Kiesel, P and Wells, JN and Murphy, LC and Keighren, MA and Marsh, JA and Lorentzen, E and Pigino, G and Mill, P}, title = {A WDR35-dependent coat protein complex transports ciliary membrane cargo vesicles to cilia.}, journal = {eLife}, volume = {10}, number = {}, pages = {}, pmid = {34734804}, issn = {2050-084X}, support = {MC_UU_00007/14/MRC_/Medical Research Council/United Kingdom ; MC_UU_12018/26/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Animals ; Chlamydomonas reinhardtii/*metabolism ; Cilia/*metabolism ; Cytoskeletal Proteins/*genetics/metabolism ; Intracellular Signaling Peptides and Proteins/*genetics/metabolism ; Mice ; Protein Binding ; Protein Transport ; }, abstract = {Intraflagellar transport (IFT) is a highly conserved mechanism for motor-driven transport of cargo within cilia, but how this cargo is selectively transported to cilia is unclear. WDR35/IFT121 is a component of the IFT-A complex best known for its role in ciliary retrograde transport. In the absence of WDR35, small mutant cilia form but fail to enrich in diverse classes of ciliary membrane proteins. In Wdr35 mouse mutants, the non-core IFT-A components are degraded and core components accumulate at the ciliary base. We reveal deep sequence homology of WDR35 and other IFT-A subunits to α and ß' COPI coatomer subunits and demonstrate an accumulation of 'coat-less' vesicles that fail to fuse with Wdr35 mutant cilia. We determine that recombinant non-core IFT-As can bind directly to lipids and provide the first in situ evidence of a novel coat function for WDR35, likely with other IFT-A proteins, in delivering ciliary membrane cargo necessary for cilia elongation.}, } @article {pmid34723068, year = {2021}, author = {Hirose, M}, title = {Predicting the Potential Applicability to Other Technical Fields Through the Linkage Between Backward and Forward Citations.}, journal = {Frontiers in research metrics and analytics}, volume = {6}, number = {}, pages = {736687}, pmid = {34723068}, issn = {2504-0537}, abstract = {This article is a modest attempt to shed some light on the question of linkages between backward and forward citations in technical fields posed by Trajtenberg et al. (1997). They found interesting similarities and high correlations between equivalent measures looking forward and backward. They also implied the linkage between distant backward and distant forward citations. There are several questions to be posed in applying their insights to Japanese patent applications, however, due to the differences in the patent classification system and the subject of citation, i.e., citations by the applicant or examiner, between the US and Japan. In addition, and most importantly, the possibility that subsequent classifications may match, even if the first classification is different, is unavoidable with existing measurement methods of technical distance. In order to investigate these research questions, the author proposes a new measurement method for the technological proximity between examiner's citations and their originating patents using IPC-based patent classifications. Using such a proposed method, the author created two hypotheses and tested them for about 14,000 examined patent applications filed in 2008 with the JPO. As a result of testing Hypothesis I, the author confirmed that Trajtenberg et al.'s insights can be applied to Japanese patent applications using citations by the examiners and IPC-based patent classifications. In other words, it was confirmed that patent applications citing backward citations categorized in a technical field distant from the invention are more likely to be cited by forward citations categorized in a technical field distant from the invention. As a result of the verification of Hypothesis Ⅱ, it was further confirmed in some technical fields that the backward citations categorized in a technical field distant from the invention are more likely to be in the same technical field as the forward citations categorized in a technical field distant from the invention. The author believes that these verified results indicate the possibilities of using backward citations as a starting point from which we can find patent applications for inventions at an early stage with potential applicability to other technical fields.}, } @article {pmid34714215, year = {2021}, author = {Andkjær, S and Klein-Wengel, TT and Ishøi, A and Bjørk Petersen, C}, title = {Being and doing in the outdoors brings something extra! Evaluating the Danish Healthy in Nature Project.}, journal = {International journal of qualitative studies on health and well-being}, volume = {16}, number = {1}, pages = {1983947}, pmid = {34714215}, issn = {1748-2631}, mesh = {Adult ; Denmark ; *Health Promotion ; *Health Status ; Humans ; Qualitative Research ; Surveys and Questionnaires ; }, abstract = {PURPOSE: Little is known of the potential of using nature and outdoor activities in relation to community-based health promotion programmes. This study seeks a better understanding of how people with mental or chronic physical health problems experience a local outdoor health promotion or rehabilitation programmes and a better understanding of how these programs contribute to the participant's health and well-being.

METHODS: The study is based on data from the Healthy in Nature project targeting adults with chronic physical health problems and adults with mental health problems. Data was collected using a qualitative multiple case study design involving five selected cases with both qualitative interviews and observation. Data was analysed using Braun et al.'s 6-phase guide to qualitative reflexive thematic analysis, employing Self-Determination Theory as a theoretical framework. Results: Overall, the participants in the two groups experienced increased competence, autonomy, and relatedness, and the participants expressed the importance of both being in a natural environment and doing outdoor activities (friluftsliv).

CONCLUSIONS: The study makes a valuable contribution to the field of health promotion and rehabilitation pointing to nature and friluftsliv as important elements that offer great potential to community-based health promotion.}, } @article {pmid34711227, year = {2021}, author = {Ketcher, D and Lutgendorf, SK and Leighton, S and Matzo, M and Carter, J and Peddireddy, A and Karlan, BY and Tew, WP and Sood, AK and Shinn, EH}, title = {Attributions of survival and methods of coping of long-term ovarian cancer survivors: a qualitative study.}, journal = {BMC women's health}, volume = {21}, number = {1}, pages = {376}, pmid = {34711227}, issn = {1472-6874}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; T32 CA090314/CA/NCI NIH HHS/United States ; }, mesh = {Adaptation, Psychological ; *Cancer Survivors ; Female ; Humans ; *Ovarian Neoplasms ; Qualitative Research ; Survivors ; }, abstract = {BACKGROUND: Only 8-23% of advanced epithelial ovarian cancer patients survive for 10 years or longer. Given the need for targeted interventions to improve survival, we interviewed this relatively rare survivor population to gain personalized insights into the reasons for their survival. The aim of this study was to characterize subjective attributions of survival and specific coping mechanisms long-term survivors of ovarian cancer.

METHODS: Twenty-two semi-structured, qualitative interviews assessing survival attributions and coping strategies were conducted from April to November 2014. Data were analyzed in a multistep process using ATLAS.ti.8: codes were identified during review of the transcripts and refined with literature review; the frequency of codes and code co-occurrence was calculated, and codes were grouped into themes. Resulting themes were checked by a national leader of an ovarian cancer advocacy organization and compared against available literature.

RESULTS: Thematic analysis found that participants credited their long-term survival to a variety of factors including medical, social, religious/spiritual, and lifestyle/personal characteristics. Some participants rejected these same attributions, concluding that the reason for survival was due to luck or unknowable. Several of Carver et al.'s theoretical dimensions of coping were evident in our sample: planning, positive reinterpretation, social support, religion and acceptance whereas three relatively new strategies were uncovered: conserving emotional energy, value-based activity coping, and self-care.

CONCLUSIONS: Long-term survivors' perspectives were largely consistent with those of newly diagnosed ovarian cancer patients and ovarian cancer survivors of shorter duration. However, the long-term survivors were also willing to reject conventional attributions for survival and recognized the importance of disciplined self-preservational coping strategies.}, } @article {pmid34708408, year = {2022}, author = {Minor, NR and Dougherty, PJ and Taylor, SA and Carling, MD}, title = {Estimating hybridization in the wild using citizen science data: A path forward.}, journal = {Evolution; international journal of organic evolution}, volume = {76}, number = {2}, pages = {362-372}, doi = {10.1111/evo.14392}, pmid = {34708408}, issn = {1558-5646}, mesh = {Animals ; Birds/genetics ; *Citizen Science ; Hybridization, Genetic ; Nucleic Acid Hybridization ; Seasons ; }, abstract = {Genomic evidence of introgression in natural populations has reinvigorated the study of hybridization in recent years. Still, it is largely unknown how frequently individual organisms mate across species lines. Recently, Justyn et al. suggested that eBird, one of the world's largest citizen science databases, may supply adequate data for estimating hybridization rates. Here, we compare Justyn et al.'s estimates-and their conclusions that hybridization is rare-with estimates from museum and molecular data. We also estimate hybridization using eBird observations from areas and times when hybridization is possible, namely, in contact zones during the breeding season. These estimates are all considerably higher than those reported in Justyn et al., emphasizing that inferences from multiple datasets can differ radically. Finally, we demonstrate an approach for predicting the location of hybrid zones using eBird data, which can be done with high confidence and with unprecedented resolution. We show that citizen science data, far from settling the question of how frequently bird species hybridize, instead offer a promising step toward more focused study of hybrid zones.}, } @article {pmid34671783, year = {2021}, author = {Sanchez-Segado, S and Lectez, S and Jha, A and Stackhouse, S}, title = {A comparison of methods for the estimation of the enthalpy of formation of rare earth compounds.}, journal = {Physical chemistry chemical physics : PCCP}, volume = {23}, number = {42}, pages = {24273-24281}, doi = {10.1039/d1cp03280a}, pmid = {34671783}, issn = {1463-9084}, abstract = {Rare earth elements are helping drive the global transition towards a greener economy. However, the way in which they are produced is far from being considered green. One of the major obstacles to developing greener production methods and the design of novel processes and materials involving rare earth elements is the limited thermodynamic data available. In the present work, we apply a suite of methods to estimate the enthalpy of formation of several rare earth compounds, including a new method based on a linear relationship, established by the authors. Experimental values of the enthalpy of formation of LnCl3, LnOCl, LnPO4, Ln2O2S, Ln2O2CO3 and NaLnO2 were collated and used to assess the accuracy of the different methods, which were then used to predict values for compounds for which no data exists. It is shown that Mostafa et al.'s group contribution method and the linear relationship proposed by the authors give the lowest mean absolute error (<9%). The volume based thermodynamics (VBT) method yields estimates with absolute mean errors below 16.0% for LnPO4 and Ln2O2S, but above 26.0% for other compounds. Correction of the VBT method using an improved estimate of the Madelung energy for the calculation of the lattice enthalpy decreases the absolute mean error below 12.0% for all compounds except LnPO4. These complementary methods provide options for calculating the enthalpy of formation of rare earth compounds, depending on the experimental data available and desired accuracy.}, } @article {pmid34670101, year = {2021}, author = {Focht Garand, KL and Suiter, DM and Reyes, S and York, JD and Chen, IA}, title = {Aspiration Screening in Motor Neuron Disease: Preliminary Results From Utilization of the Yale Swallow Protocol.}, journal = {American journal of speech-language pathology}, volume = {30}, number = {6}, pages = {2693-2699}, doi = {10.1044/2021_AJSLP-21-00092}, pmid = {34670101}, issn = {1558-9110}, mesh = {Aged ; Cross-Sectional Studies ; Deglutition ; *Deglutition Disorders/diagnosis ; Female ; Fluoroscopy ; Humans ; Male ; Middle Aged ; *Motor Neuron Disease/complications/diagnosis ; Predictive Value of Tests ; Video Recording ; }, abstract = {Purpose Dysphagia is a common symptom experienced by patients with motor neuron disease (MND). The Yale Swallow Protocol (YSP) is a validated screening instrument for identifying patients at risk for aspiration. The purpose of this exploratory cross-sectional, multicenter study was to investigate how the YSP results in identifying aspiration risk in patients with MND in comparison with aspiration observed during a videofluoroscopic swallow study (VFSS). Method Participants referred for VFSS as part of clinical management were recruited from four specialized MND clinics. All participants were administered the YSP immediately prior to the VFSS by a speech-language pathologist, with results recorded as pass or fail. Aspiration on VFSS was determined using the Penetration-Aspiration Scale (scores 6-8). A 2 × 2 contingency table was constructed to compare results of YSP with those on VFSS. Results Thirty-one patients with MND (13 males, 18 females; M age = 64 ± 12 years) referred for VFSS participated in this study. Of the 22 patients who failed the YSP, interrupted drinking was the most frequent reason (65%). Compared to the VFSS, the YSP yielded a sensitivity of 80%, a specificity of 33%, positive predictive value of 36%, and negative predictive value of 78%. Conclusions The YSP is a simple tool and easy to utilize and has a high sensitivity in identifying aspiration risk in amyotrophic lateral sclerosis. A future investigation with a larger sample size is needed to better investigate the utility of YSP as a screening tool for this population.}, } @article {pmid34667618, year = {2021}, author = {Shanks, DR and Vadillo, MA}, title = {Publication bias and low power in field studies on goal priming.}, journal = {Royal Society open science}, volume = {8}, number = {10}, pages = {210544}, pmid = {34667618}, issn = {2054-5703}, abstract = {Research on goal priming asks whether the subtle activation of an achievement goal can improve task performance. Studies in this domain employ a range of priming methods, such as surreptitiously displaying a photograph of an athlete winning a race, and a range of dependent variables including measures of creativity and workplace performance. Chen, Latham, Piccolo and Itzchakov (Chen et al. 2021 J. Appl. Psychol. 70, 216-253) recently undertook a meta-analysis of this research and reported positive overall effects in both laboratory and field studies, with field studies yielding a moderate-to-large effect that was significantly larger than that obtained in laboratory experiments. We highlight a number of issues with Chen et al.'s selection of field studies and then report a new meta-analysis (k = 13, N = 683) that corrects these. The new meta-analysis reveals suggestive evidence of publication bias and low power in goal priming field studies. We conclude that the available evidence falls short of demonstrating goal priming effects in the workplace, and offer proposals for how future research can provide stronger tests.}, } @article {pmid34664548, year = {2023}, author = {Horigome, T and Kurokawa, S and Sawada, K and Kudo, S and Shiga, K and Mimura, M and Kishimoto, T}, title = {Response to Morina et al.'s criticisms of Horigome et al.'s recent report on the efficacy of virtual reality exposure therapy for social anxiety disorder.}, journal = {Psychological medicine}, volume = {53}, number = {5}, pages = {2179-2180}, doi = {10.1017/S0033291721004086}, pmid = {34664548}, issn = {1469-8978}, mesh = {Humans ; *Phobia, Social/therapy ; *Virtual Reality Exposure Therapy ; *Phobic Disorders/therapy ; Anxiety Disorders/therapy ; }, } @article {pmid34661968, year = {2021}, author = {Liu, T and AgyeKum, E and Ma, S and Ye, H and Li, J and Gao, M and Ni, M and Zhang, X and Wang, X}, title = {Novel nanohybrids for effervescence enhanced magnetic solid-phase microextraction of wide-polarity organic pollutants in roasted meat samples.}, journal = {Journal of separation science}, volume = {44}, number = {24}, pages = {4313-4326}, doi = {10.1002/jssc.202100482}, pmid = {34661968}, issn = {1615-9314}, support = {//Jiangsu Postgraduate Scientific Research and Practice Innovation Program in 2020/ ; 21876125//National Natural Science Foundation of China/ ; 22076134//National Natural Science Foundation of China/ ; //Project of Suzhou City Science and Technology Bureau/ ; //Jiangsu Provincial Natural Science Foundation/ ; }, mesh = {Benzhydryl Compounds/isolation & purification ; Chromatography, High Pressure Liquid/methods ; Food Contamination/*analysis ; Limit of Detection ; *Magnetics ; Meat Products/*analysis ; Microscopy, Electron, Scanning ; Microscopy, Electron, Transmission ; *Nanostructures ; Organic Chemicals/*isolation & purification ; Phenols/isolation & purification ; Polycyclic Aromatic Hydrocarbons/isolation & purification ; Solid Phase Microextraction/*methods ; Spectrometry, Fluorescence/methods ; }, abstract = {To simultaneously and efficiently extract pollutants with differential polarities, we herein fabricated and characterized a multifunctional nanocomposite. The novel nanohybrids used NiFe2 O4 as magnetic cores, and NH2 -MIL-101(Al), β-cyclodextrin and graphene oxide as functional components combined with magnetic cores. With the aid of graphene oxide's large π-conjugated system, NH2 -MIL-101(Al)'s strong adsorption to moderately/strongly polar chemicals, and β-cyclodextrin's specific recognition effect, the nanohybrids realized synergistically efficient extraction of polyaromatic hydrocarbons and bisphenols with a log[Kow] range of 3-6. Combined with acidic and alkaline sources, the nanohybrids-based effervescent tablets were prepared. Based on effervescent reaction-enhanced nanohybrids-based efficient adsorption/extraction and high performance liquid chromatography and fluorescence detection, we successfully developed an excellent microextraction method for the simultaneous determination of both polyaromatic hydrocarbons and bisphenols in roasted meat samples. Several important variables were optimized as follows: Na2 CO3 and tartaric acid as acidic and alkaline sources, 900 μLof the mixed solvent (acetone and hexane at 2:1 by v/v) as the eluent, 5 min of elution time. Under optimized conditions, the novel method gave low limits of detection (0.07-0.30 μg kg[-1]), satisfactory recoveries (86.9-103.9%), and high precision (relative standard deviations of 1.9-6.7%) in roasted lamb, beef, pork, chicken, and sausage samples.}, } @article {pmid34641906, year = {2021}, author = {Parks, BN and Mason, J}, title = {The standardization of clinical ethics consultation and technique's "long encirclement" of humanity: a response to Brummett and Muaygil.}, journal = {Philosophy, ethics, and humanities in medicine : PEHM}, volume = {16}, number = {1}, pages = {13}, pmid = {34641906}, issn = {1747-5341}, mesh = {*Bioethics ; Ethicists ; *Ethics Consultation ; Ethics, Clinical ; Humans ; Reference Standards ; United States ; }, abstract = {In their recent article, Brummett and Muaygil reject Bishop et al.'s framing of the debate over standardization in clinical ethics consultation (CEC) "as one between pro-credentialing procedural and anti-credentialing phenomenological," claiming that this framing "amounts to a false dichotomy between two extreme approaches to CEC." Instead of accepting proceduralism and phenomenology as a binary, Brummett and Muaygil propose that these two views should be seen as the extreme ends of a spectrum upon which CEC should be done. However, as evidenced by several inconsistencies within their article, they have failed to fully appreciate the concern animating Bishop et al.'s proposal. Additionally, because of this failure, they do not seem to realize that credentialing ethicists for CEC will only create different problems in Saudi Arabia even as it possibly solves some of the current problems they identify. In this commentary, we highlight and clarify Brummet and Muaygil's five misunderstandings of Bishop et al. This leads us to conclude that while they claim to be advocating a middle way between proceduralism and phenomenology, in fact they would like for us to standardize another proceduralism, albeit one that incorporates some of the "qualitative" values of American bioethics.}, } @article {pmid34641758, year = {2023}, author = {Lam, C}, title = {The Link between Patients' Aggressive Communication and Nurses' Emotional Health Outcomes.}, journal = {Health communication}, volume = {38}, number = {5}, pages = {1033-1040}, doi = {10.1080/10410236.2021.1989788}, pmid = {34641758}, issn = {1532-7027}, mesh = {Humans ; *Emotions ; Aggression ; Communication ; Surveys and Questionnaires ; Outcome Assessment, Health Care ; *Nurses ; Job Satisfaction ; }, abstract = {The aggressive conduct of patients is a perennial problem that nurses face in health care. Studies have shown that such aggressiveness can be detrimental to the work and emotional wellbeing of nurses. Yet, the literature has had inconsistent findings; in some cases nurses are negatively affected by aggression, while in other cases nurses are not affected. Street and colleagues contended that such inconsistencies in research exist because social mechanisms embedded in communication are often not taken into consideration. This study adopts Street et al.'s pathways model and links patients' aggressive communication to nurses' emotional health outcomes, via the proximal outcome of communication satisfaction and the intermediate outcome of organizational identity. Results support Street et al.'s postulation and demonstrates that patients' aggressive communication does not have a direct effect on nurses' emotional health. Instead, the effect is indirect, mediated by communication satisfaction and organizational identity.}, } @article {pmid34636588, year = {2021}, author = {Gangestad, SW and Dinh, T}, title = {Robust evidence for moderation of ovulatory shifts by partner attractiveness in Arslan et al.'s (2020) data.}, journal = {Journal of personality and social psychology}, volume = {121}, number = {2}, pages = {432-440}, doi = {10.1037/pspp0000305}, pmid = {34636588}, issn = {1939-1315}, support = {//National Science Foundation/ ; }, mesh = {Female ; Fertility ; Humans ; Libido ; Male ; Ovulation ; *Sexual Behavior ; *Sexual Partners ; }, abstract = {Arslan et al. (2020) conducted a large-scale, preregistered daily diary study on over 400 normally ovulating women. Of core interest were hypotheses that women's ratings of their partner's sexual attractiveness moderate associations of fertility status with women's own extrapair sexual desires, their own interest in in-pair sex, and their partners' mate retention tactics. The authors claim that "no evidence for moderator effects" (p. 426) was found. In fact, their own analyses reported in their supplementary material show robust evidence for moderation effects. Moreover, a new reanalysis using a more comprehensive composite measure of male partner sexual attractiveness yielded even stronger results. Effect size estimates are consistent with the existence of large, meaningful moderation effects, revealing that this study actually does show evidence of moderation effects. Additional analyses show similarly strong moderator effects on male proprietariness. We discuss the findings in the context of reliance on binary (significant vs. nonsignificant) labels and the pitfalls of underreporting effects. (PsycInfo Database Record (c) 2021 APA, all rights reserved).}, } @article {pmid34634372, year = {2022}, author = {Fraser, CN and Möller, SP and Knowles, SR}, title = {Understanding disease-specific and non-specific factors predicting disordered eating in adults with coeliac disease.}, journal = {Appetite}, volume = {168}, number = {}, pages = {105744}, doi = {10.1016/j.appet.2021.105744}, pmid = {34634372}, issn = {1095-8304}, mesh = {Adult ; *Bulimia ; *Celiac Disease/complications ; *Feeding and Eating Disorders/complications ; Female ; Humans ; Male ; Middle Aged ; *Psychological Distress ; Surveys and Questionnaires ; }, abstract = {An adverse relationship between coeliac disease and the development of disordered eating patterns is well established. The aim of this study was to replicate and extend Satherley et al.'s (2016) study exploring coeliac-specific and non-specific factors predicting disordered eating. An online survey was completed by 187 adults with coeliac disease (90.4% female; Mean age = 48.92; Mean years living with coeliac disease = 11.86). Results indicated that greater disordered eating correlated with being female, poorer dietary adherence, greater gastrointestinal and psychological symptoms, and more coeliac-related food concerns. Hierarchical regression analyses found that psychological distress remained the only predictor of disordered eating when both coeliac-specific and non-specific factors were considered. Age, body mass index, psychological distress, years with coeliac disease and dietary nonadherence were found to significantly predict binge eating severity. The findings suggest that psychological distress is a risk factor for disordered eating in coeliac disease and that binge eating behaviours may be a particularly relevant factor for dietary nonadherence in those living with coeliac disease.}, } @article {pmid34629321, year = {2022}, author = {Feldner, HA and VanPuymbrouck, L and Friedman, C}, title = {Explicit and implicit disability attitudes of occupational and physical therapy assistants.}, journal = {Disability and health journal}, volume = {15}, number = {1}, pages = {101217}, doi = {10.1016/j.dhjo.2021.101217}, pmid = {34629321}, issn = {1876-7583}, mesh = {Attitude ; Attitude of Health Personnel ; *Persons with Disabilities ; Health Personnel ; Humans ; *Physical Therapist Assistants ; Prejudice ; }, abstract = {BACKGROUND: Reduction of explicit and implicit bias in healthcare providers is a critical issue faced by our society in moving toward more equitable and culturally appropriate health and rehabilitation care. Because resources for OT and PT services are limited and shortages in these professions exist, direct care provision by occupational and physical therapist assistants (OTA/PTA) is on the rise and valued in comprehensive rehabilitation practice. It is important to consider attitudes and biases of OTA/PTA, as they are directly involved in provision of rehabilitation services for people with disabilities.

OBJECTIVE: This study examined the explicit and implicit disability attitudes of a large cross-section of OTA/PTA.

METHODS: Secondary data analysis was completed using data from 6113 OTA/PTA from the Project Implicit Disability Attitudes Implicit Association Test. Implicit attitudes were calculated and OTA/PTA explicit and implicit disability attitudes were compared. Results were further categorized using an adapted version of Son Hing et al.'s two-dimensional model of prejudice.

RESULTS: Findings revealed the majority of OTA/PTA reported having no explicit preference for people with disabilities or nondisabled people. However, the majority of OTA/PTA were aversive ableists, indicating low explicit and high implicit bias.

CONCLUSIONS: Though explicit bias is lower in OTA/PTA, implicit bias is strong, indicating that people with disabilities face bias that may influence clinical interactions, and may be reproduced in professional education, practice, and policy. Concrete action must be taken to recognize and address disability bias to reduce health disparities in people with disabilities.}, } @article {pmid34622705, year = {2021}, author = {Barnhart, T and Rovito, MJ and Maresca, M and Rovito, K}, title = {Marginalized Males, Disparate COVID-19 Outcomes, and Health Equity: A Profile of Highest Risk.}, journal = {American journal of men's health}, volume = {15}, number = {5}, pages = {15579883211050523}, pmid = {34622705}, issn = {1557-9891}, mesh = {*COVID-19 ; *Health Equity ; Humans ; Male ; Public Health ; SARS-CoV-2 ; }, abstract = {This paper is a direct response to Smith et al.'s (2020) call for more insight into health equity concerns pertaining to COVID-19 outcomes. The goal of this discussion is to offer the field with an evidence-informed 'avatar' representing the most-impacted group as it pertains to COVID-19 mortality and morbidity. Policy and practice implications are offered as a call to action for public health professionals to support these most impacted and highest risk communities.}, } @article {pmid34613823, year = {2021}, author = {Riska, KM and Peskoe, SB and Gordee, A and Kuchibhatla, M and Smith, SL}, title = {Response to Powell et al., "Do Hearing Aids Prevent Falls? Commentary on Study From the National Health and Nutrition Examination Survey".}, journal = {American journal of audiology}, volume = {30}, number = {4}, pages = {1148-1149}, pmid = {34613823}, issn = {1558-9137}, support = {R21 DC018616/DC/NIDCD NIH HHS/United States ; UL1 TR002553/TR/NCATS NIH HHS/United States ; }, mesh = {Accidental Falls/prevention & control ; *Hearing Aids ; *Hearing Loss/prevention & control ; Humans ; Nutrition Surveys ; Self Report ; }, abstract = {This letter serves to respond to Powell et al.'s (2021) letter to the editor regarding our recent publication, "Preliminary Evidence on the Impact of Hearing Aid Use on Falls Risk in Individuals With Self-Reported Hearing Loss." In our letter, we respond to key concerns and commentary raised by the authors.}, } @article {pmid34612066, year = {2022}, author = {Chassid-Segin, M and Gueta, K and Ronel, N}, title = {Maintaining Normative Functioning Alongside Drug Use: The Recognition of Harms and Adoption of Change Strategies.}, journal = {International journal of offender therapy and comparative criminology}, volume = {66}, number = {16}, pages = {1879-1897}, doi = {10.1177/0306624X211049180}, pmid = {34612066}, issn = {1552-6933}, mesh = {Humans ; *Drug Users ; *Substance-Related Disorders ; }, abstract = {The current study examined drug users' perspectives on strategies that helped them to maintain normative functioning or resolve impaired functioning. We interviewed 29 drug users who described themselves as functioning normatively while using drugs on a regular basis until they experienced harms or raised concerns of future harms. The content analysis showed that the users maintain their normative functioning through diverse strategies that can be located on a continuum. This continuum was conceptualized as "normative functioning management" based on White et al.'s concept of "recovery management." This study found an ongoing continuum through self-management and social interaction consisting of three regions: the management of normative functioning, the recognition of the harm of drug use to functioning, and the subsequent adoption of change strategies for maintaining normative functioning. This continuum may provide a more nuanced theoretical understanding of the phenomenon of drug users with normative functioning and is therefore relevant for counselors encountering such users in their practice. This study highlights inner resources such as self-awareness and social interaction that help functioning users to maintain their normative functioning and fulfill basic obligations in their normal routines, that is, preserving their professional status, family lives, and relationships.}, } @article {pmid34611708, year = {2022}, author = {Matenge, S and Sturgiss, E and Desborough, J and Hall Dykgraaf, S and Dut, G and Kidd, M}, title = {Ensuring the continuation of routine primary care during the COVID-19 pandemic: a review of the international literature.}, journal = {Family practice}, volume = {39}, number = {4}, pages = {747-761}, pmid = {34611708}, issn = {1460-2229}, mesh = {*COVID-19/epidemiology ; Delivery of Health Care ; Humans ; Pandemics ; Primary Health Care ; *Telemedicine ; }, abstract = {BACKGROUND: The COVID-19 pandemic has resulted in the diversion of health resources away from routine primary care delivery. This disruption of health services has necessitated new approaches to providing care to ensure continuity.

OBJECTIVES: To summarize changes to the provision of routine primary care services during the pandemic.

METHODS: Rapid literature review using PubMed/MEDLINE, SCOPUS, and Cochrane. Eligible studies were based in primary care and described practice-level changes in the provision of routine care in response to COVID-19. Relevant data addressing changes to routine primary care delivery, impact on primary care functions and challenges experienced in adjusting to new approaches to providing care, were obtained from included studies. A narrative summary was guided by Burns et al.'s framework for primary care provision in disasters.

RESULTS: Seventeen of 1,699 identified papers were included. Studies reported on telehealth use and public health measures to maintain safe access to routine primary care, including providing COVID-19 screening, and establishing dedicated care pathways for non-COVID and COVID-related issues. Acute and urgent care were prioritized, causing disruptions to chronic disease management and preventive care. Challenges included telehealth use including disparities in access and practical difficulties in assessing patients, personal protective equipment shortages, and financial solvency of medical practices.

CONCLUSIONS: Substantial disruptions to routine primary care occurred due to the COVID-19 pandemic. Primary care practices' rapid adaptation, often with limited resources and support, demonstrates agility and innovative capacity. Findings underscore the need for timely guidance and support from authorities to optimize the provision of comprehensive routine care during pandemics.}, } @article {pmid34607337, year = {2021}, author = {Wang, J and Cao, S and Yang, L and Zhang, Y and Xing, K and Lu, X and Xu, J}, title = {Metastable marcasite NiSe2 nanodendrites on carbon fiber clothes to suppress polysulfide shuttling for high-performance lithium-sulfur batteries.}, journal = {Nanoscale}, volume = {13}, number = {39}, pages = {16487-16498}, doi = {10.1039/d1nr04879a}, pmid = {34607337}, issn = {2040-3372}, abstract = {The incorporation of catalytic components is a promising strategy to promote redox reaction kinetics and suppress polysulfide shuttling for high-performance lithium-sulfur batteries (LSBs). In this work, metastable marcasite NiSe2 nanodendrites grown on carbon fiber clothes (m-NiSe2/CFC) were synthesized to improve chemical adsorption and electrocatalytic activity towards lithium polysulfides. The multifunctional m-NiSe2/CFC film was utilized as both the interlayer and the three-dimensional (3D) current collector in LSBs. In comparison with the stable pyrite NiSe2 nanodendrite-covered CFC (p-NiSe2/CFC) counterpart, the m-NiSe2/CFC film exhibits even stronger chemisorption, higher catalytic activity and faster reaction kinetics, thereby resulting in significantly improved lithium storage performance. The Al@S/rGO@m-NiSe2/CFC cell has a high reversible capacity of 1646 mA h g[-1] at 0.2C, a high QL/QH ratio of 3.00 at 0.2C, a high rate capability of 900 mA h g[-1] at 4C, and an outstanding cyclic stability exhibiting a low capacity decay of 0.028% per cycle for 600 cycles at 4C. Moreover, a symmetrically sandwiched cathode of m-NiSe2/CFC@S/rGO@m-NiSe2/CFC was designed for high sulfur loading LSBs (4.5 mg cm[-2]) with superior electrochemical performance of 3.73 mA h cm[-2] after 100 cycles at 1C rate. Our work opens up a new opportunity to enhance the electrochemical performance of LSBs by phase engineering of NiSe2 catalysts in sandwiched structural cathodes.}, } @article {pmid34596767, year = {2021}, author = {Galassi, FM and Torrisi, E and Varotto, E}, title = {Comment on Turgut et al.'s Three mythic giants for common fetal malformation called "cyclopia": Polyphemus, Tepegöz, and Grendel.}, journal = {Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery}, volume = {37}, number = {12}, pages = {3665-3666}, pmid = {34596767}, issn = {1433-0350}, mesh = {*Holoprosencephaly ; Humans ; }, } @article {pmid34592575, year = {2021}, author = {Darling, EK and Easterbrook, R and Grenier, LN and Malott, A and Murray-Davis, B and Mattison, CA}, title = {Lessons learned from the implementation of Canada's first alongside midwifery unit: A qualitative explanatory study.}, journal = {Midwifery}, volume = {103}, number = {}, pages = {103146}, doi = {10.1016/j.midw.2021.103146}, pmid = {34592575}, issn = {1532-3099}, mesh = {Female ; Health Personnel ; Humans ; Leadership ; *Midwifery ; Ontario ; Pregnancy ; Qualitative Research ; }, abstract = {BACKGROUND: In July 2018, Canada's first midwife-led alongside midwifery unit (AMU) opened at Markham Stouffville Hospital (MSH) in Markham, Ontario. Our objectives were to examine how the conditions at MSH made it possible for the hospital to create the first AMU in Canada and to identify lessons to inform spread by examining how characteristics of the intervention, the inner and outer settings, the individuals involved, and the processes used influenced the MSH-AMU implementation process.

METHODS: We conducted key informant interviews and document analysis using Yin's research methods. We used the Consolidated Framework for Implementation Research to conceptualize the study and develop semi-structured interview guides. We recruited key informants, including midwives and other health professionals, hospital leaders, leaders of midwifery organizations, and consumers, by email using both purposive and respondent driven sampling. Interviews were digitally recorded and professionally transcribed. We identified documents through key informants and searches of Nexis Uni, Hansard, and Google databases. We analyzed the data using a coding framework based on Greenhalgh et al.'s evidence-informed theory of the diffusion of innovations.

RESULTS: Between November 2018 and February 2019, we conducted fifteen key informant interviews. We identified thirteen relevant documentary sources of evidence, including news media coverage, website content, Ontario parliamentary records, and hospital documents. Conditions that influenced implementation of the AMU fell within the following domains from Greenhalgh's diffusion of innovations theory: the innovation, the outer context, the inner context - system antecedents for innovation and system readiness for innovation, communication and influence, linkage - design phase and implementation stage, and the implementation process. While several unique features of MSH supported innovation, factors that could be adopted elsewhere include organizational investment in the development of midwifery leadership skills, intentional use of change management theory, broad stakeholder involvement in the design and implementation processes, and frequent, open communication.

CONCLUSIONS: The example of the MSH-AMU illustrates the value of utilizing best practices with respect to change management and system transformation and demonstrates the potential value of using implementation theory to drive the successful implementation of AMUs. Lessons learned from the MSH-AMU can inform successful spread of this innovative service model.}, } @article {pmid34591296, year = {2022}, author = {Li, ML and Luo, J and Ellis, MW and Riaz, M and Ajaj, Y and Qyang, Y}, title = {Methods for Differentiating hiPSCs into Vascular Smooth Muscle Cells.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {2375}, number = {}, pages = {21-34}, pmid = {34591296}, issn = {1940-6029}, mesh = {Cell Differentiation ; Humans ; *Induced Pluripotent Stem Cells ; *Muscle, Smooth, Vascular ; Myocytes, Smooth Muscle ; Tissue Engineering ; }, abstract = {Despite numerous efforts to generate vascular tissues that recapitulate the physiological characteristics of native vessels, vascular cell source remains one of the principal challenges in the construction of tissue-engineered vascular grafts (TEVGs). Human pluripotent stem cells, therefore, represent an indispensable source to supply a large production of vascular smooth muscle cells (VSMCs) for cell-based therapy. In particular, human induced pluripotent stem cells (hiPSCs) generated from the same individual have opened up new avenues of achieving patient specificity through the derivation of autologous and immunocompatible VSMCs. This book chapter will detail three representative methods of differentiating hiPSCs into VSMCs that are structurally and functionally mature for TEVG engineering. Luo et al. reported an embryoid body (EB)-based approach to generate a robust, large-scale production of mature, functional hiPSC-derived VSMCs as a cell replacement for vascular tissue engineering. EB formation has an advantage of resembling early embryonic development and allowing cellular interactions in three dimensions. Cheung et al. established a system to produce embryological origin-specific hiPSC-derived VSMCs from the neuroectoderm, lateral plate mesoderm, and paraxial mesoderm lineages in a chemically defined manner. This allows site-specific vascular disease modeling. Moreover, Eoh et al. followed Wanjare et al.'s method to construct hiPSC-derived VSMCs using monolayer cultures of extracellular matrix proteins, with the addition of a pulsatile flow for the secretion of mature, organized elastic fibers. The generation of TEVGs, powered by the unlimited supply of hiPSC-derived VSMCs, has begun a new era in cellular therapy for vascular bypass and defective vessel segment replacement, aimed at addressing millions of cases of cardiovascular diseases across the globe.}, } @article {pmid34591284, year = {2022}, author = {Hoffman, P and Lambon Ralph, MA and Rogers, TT}, title = {Semantic diversity is best measured with unscaled vectors: Reply to Cevoli, Watkins and Rastle (2020).}, journal = {Behavior research methods}, volume = {54}, number = {4}, pages = {1688-1700}, pmid = {34591284}, issn = {1554-3528}, support = {MC_UU_00005/18/MRC_/Medical Research Council/United Kingdom ; MC_UU_00030/9/MRC_/Medical Research Council/United Kingdom ; BB/T004444/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Humans ; *Judgment ; *Semantics ; }, abstract = {Semantic diversity refers to the degree of semantic variability in the contexts in which a particular word is used. We have previously proposed a method for measuring semantic diversity based on latent semantic analysis (LSA). In a recent paper, Cevoli et al. (2020) attempted to replicate our method and obtained different semantic diversity values. They suggested that this discrepancy occurred because they scaled their LSA vectors by their singular values, while we did not. Using their new results, they argued that semantic diversity is not related to ambiguity in word meaning, as we originally proposed. In this reply, we demonstrate that the use of unscaled vectors provides better fits to human semantic judgements than scaled ones. Thus we argue that our original semantic diversity measure should be preferred over the Cevoli et al. version. We replicate Cevoli et al.'s analysis using the original semantic diversity measure and find (a) our original measure is a better predictor of word recognition latencies than the Cevoli et al. equivalent and (b) that, unlike Cevoli et al.'s measure, our semantic diversity is reliably associated with a measure of polysemy based on dictionary definitions. We conclude that the Hoffman et al. semantic diversity measure is better-suited to capturing the contextual variability among words and that words appearing in a more diverse set of contexts have more variable semantic representations. However, we found that homonyms did not have higher semantic diversity values than non-homonyms, suggesting that the measure does not capture this special case of ambiguity.}, } @article {pmid34590580, year = {2021}, author = {Harada, A and Matsumoto, S and Yasumizu, Y and Shojima, K and Akama, T and Eguchi, H and Kikuchi, A}, title = {Localization of KRAS downstream target ARL4C to invasive pseudopods accelerates pancreatic cancer cell invasion.}, journal = {eLife}, volume = {10}, number = {}, pages = {}, pmid = {34590580}, issn = {2050-084X}, mesh = {ADP-Ribosylation Factors/*genetics/metabolism ; Aged ; Aged, 80 and over ; Animals ; Female ; *Gene Expression Regulation, Neoplastic ; Humans ; Male ; Mice ; Middle Aged ; Neoplasm Invasiveness/*genetics ; Pancreatic Neoplasms/*genetics ; Proto-Oncogene Proteins p21(ras)/*genetics/metabolism ; Pseudopodia/*physiology ; Tumor Cells, Cultured ; }, abstract = {Pancreatic cancer has a high mortality rate due to metastasis. Whereas KRAS is mutated in most pancreatic cancer patients, controlling KRAS or its downstream effectors has not been succeeded clinically. ARL4C is a small G protein whose expression is induced by the Wnt and EGF-RAS pathways. In the present study, we found that ARL4C is frequently overexpressed in pancreatic cancer patients and showed that its localization to invasive pseudopods is required for cancer cell invasion. IQGAP1 was identified as a novel interacting protein for ARL4C. ARL4C recruited IQGAP1 and its downstream effector, MMP14, to invasive pseudopods. Specific localization of ARL4C, IQGAP1, and MMP14 was the active site of invasion, which induced degradation of the extracellular matrix. Moreover, subcutaneously injected antisense oligonucleotide against ARL4C into tumor-bearing mice suppressed metastasis of pancreatic cancer. These results suggest that ARL4C-IQGAP1-MMP14 signaling is activated at invasive pseudopods of pancreatic cancer cells.}, } @article {pmid34588076, year = {2021}, author = {Savage, PE and Loui, P and Tarr, B and Schachner, A and Glowacki, L and Mithen, S and Fitch, WT}, title = {Toward inclusive theories of the evolution of musicality.}, journal = {The Behavioral and brain sciences}, volume = {44}, number = {}, pages = {e121}, doi = {10.1017/S0140525X21000042}, pmid = {34588076}, issn = {1469-1825}, support = {R43 AG078012/AG/NIA NIH HHS/United States ; }, mesh = {*Adaptation, Physiological ; Biological Evolution ; Humans ; *Music ; }, abstract = {We compare and contrast the 60 commentaries by 109 authors on the pair of target articles by Mehr et al. and ourselves. The commentators largely reject Mehr et al.'s fundamental definition of music and their attempts to refute (1) our social bonding hypothesis, (2) byproduct hypotheses, and (3) sexual selection hypotheses for the evolution of musicality. Instead, the commentators generally support our more inclusive proposal that social bonding and credible signaling mechanisms complement one another in explaining cooperation within and competition between groups in a coevolutionary framework (albeit with some confusion regarding terminologies such as "byproduct" and "exaptation"). We discuss the proposed criticisms and extensions, with a focus on moving beyond adaptation/byproduct dichotomies and toward testing of cross-species, cross-cultural, and other empirical predictions.}, } @article {pmid34588067, year = {2021}, author = {Ravignani, A}, title = {Isochrony, vocal learning, and the acquisition of rhythm and melody.}, journal = {The Behavioral and brain sciences}, volume = {44}, number = {}, pages = {e88}, doi = {10.1017/S0140525X20001478}, pmid = {34588067}, issn = {1469-1825}, mesh = {Humans ; Learning ; *Music ; }, abstract = {A cross-species perspective can extend and provide testable predictions for Savage et al.'s framework. Rhythm and melody, I argue, could bootstrap each other in the evolution of musicality. Isochrony may function as a temporal grid to support rehearsing and learning modulated, pitched vocalizations. Once this melodic plasticity is acquired, focus can shift back to refining rhythm processing and beat induction.}, } @article {pmid34588062, year = {2021}, author = {Bowling, DL and Hoeschele, M and Dunn, JC}, title = {Progress without exclusion in the search for an evolutionary basis of music.}, journal = {The Behavioral and brain sciences}, volume = {44}, number = {}, pages = {e97}, pmid = {34588062}, issn = {1469-1825}, support = {K01 MH122730/MH/NIMH NIH HHS/United States ; }, mesh = {Biological Evolution ; Humans ; *Music ; }, abstract = {Mehr et al.'s hypothesis that the origins of music lie in credible signaling emerges here as a strong contender to explain early adaptive functions of music. Its integration with evolutionary biology and its specificity mark important contributions. However, much of the paper is dedicated to the exclusion of popular alternative hypotheses, which we argue is unjustified and premature.}, } @article {pmid34588056, year = {2021}, author = {Trehub, SE}, title = {Challenging infant-directed singing as a credible signal of maternal attention.}, journal = {The Behavioral and brain sciences}, volume = {44}, number = {}, pages = {e117}, doi = {10.1017/S0140525X20001442}, pmid = {34588056}, issn = {1469-1825}, mesh = {Arousal ; Attention ; Female ; Humans ; Infant ; Mothers ; *Music ; *Singing ; }, abstract = {I challenge Mehr et al.'s contention that ancestral mothers were reluctant to provide all the attention demanded by their infants. The societies in which music emerged likely involved foraging mothers who engaged in extensive infant carrying, feeding, and soothing. Accordingly, their singing was multimodal, its rhythms aligned with maternal movements, with arousal regulatory consequences for singers and listeners.}, } @article {pmid34588046, year = {2021}, author = {Yifan Zou, I and Wang, WS}, title = {Music as social bonding: A cross-cultural perspective.}, journal = {The Behavioral and brain sciences}, volume = {44}, number = {}, pages = {e95}, doi = {10.1017/S0140525X20001326}, pmid = {34588046}, issn = {1469-1825}, mesh = {Cross-Cultural Comparison ; Humans ; *Music ; Social Identification ; }, abstract = {We extend Savage et al.'s music and social bonding hypothesis by examining it in the context of Chinese music. First, top-down functions such as music as political instrument should receive more attention. Second, solo performance can serve as important cues for social identity. Third, a right match between the tones in lyrics and music contributes also to social bonding.}, } @article {pmid34588021, year = {2021}, author = {Wood, C}, title = {Musical bonds are orthogonal to symbolic language and norms.}, journal = {The Behavioral and brain sciences}, volume = {44}, number = {}, pages = {e119}, doi = {10.1017/S0140525X20001272}, pmid = {34588021}, issn = {1469-1825}, mesh = {Humans ; Language ; *Music ; }, abstract = {Both Mehr et al.'s credible signaling hypothesis and Savage et al.'s music and social bonding hypothesis emphasize the role of multilevel social structures in the evolution of music. Although empirical evidence preferentially supports the social bonding hypothesis, rhythmic music may enable bonding in a way uniquely fitted to the normative and language-based character of multilevel human societies.}, } @article {pmid34584092, year = {2021}, author = {Dilliott, AA and Abdelhady, A and Sunderland, KM and Farhan, SMK and Abrahao, A and Binns, MA and Black, SE and Borrie, M and Casaubon, LK and Dowlatshahi, D and Finger, E and Fischer, CE and Frank, A and Freedman, M and Grimes, D and Hassan, A and Jog, M and Kumar, S and Kwan, D and Lang, AE and Mandzia, J and Masellis, M and McIntyre, AD and Pasternak, SH and Pollock, BG and Rajji, TK and Rogaeva, E and Sahlas, DJ and Saposnik, G and Sato, C and Seitz, D and Shoesmith, C and Steeves, TDL and Swartz, RH and Tan, B and Tang-Wai, DF and Tartaglia, MC and Turnbull, J and Zinman, L and , and Hegele, RA}, title = {Contribution of rare variant associations to neurodegenerative disease presentation.}, journal = {NPJ genomic medicine}, volume = {6}, number = {1}, pages = {80}, pmid = {34584092}, issn = {2056-7944}, support = {0000045188//Ontario Brain Institute (Institut Ontarien du Cerveau)/ ; 0000045188//Ontario Brain Institute (Institut Ontarien du Cerveau)/ ; 0000045188//Ontario Brain Institute (Institut Ontarien du Cerveau)/ ; 0000045188//Ontario Brain Institute (Institut Ontarien du Cerveau)/ ; 0000045188//Ontario Brain Institute (Institut Ontarien du Cerveau)/ ; 0000045188//Ontario Brain Institute (Institut Ontarien du Cerveau)/ ; 0000045188//Ontario Brain Institute (Institut Ontarien du Cerveau)/ ; 0000045188//Ontario Brain Institute (Institut Ontarien du Cerveau)/ ; 0000045188//Ontario Brain Institute (Institut Ontarien du Cerveau)/ ; 0000045188//Ontario Brain Institute (Institut Ontarien du Cerveau)/ ; 0000045188//Ontario Brain Institute (Institut Ontarien du Cerveau)/ ; 0000045188//Ontario Brain Institute (Institut Ontarien du Cerveau)/ ; 0000045188//Ontario Brain Institute (Institut Ontarien du Cerveau)/ ; 0000045188//Ontario Brain Institute (Institut Ontarien du Cerveau)/ ; 0000045188//Ontario Brain Institute (Institut Ontarien du Cerveau)/ ; 0000045188//Ontario Brain Institute (Institut Ontarien du Cerveau)/ ; 0000045188//Ontario Brain Institute (Institut Ontarien du Cerveau)/ ; 0000045188//Ontario Brain Institute (Institut Ontarien du Cerveau)/ ; 0000045188//Ontario Brain Institute (Institut Ontarien du Cerveau)/ ; 0000045188//Ontario Brain Institute (Institut Ontarien du Cerveau)/ ; 0000045188//Ontario Brain Institute (Institut Ontarien du Cerveau)/ ; 0000045188//Ontario Brain Institute (Institut Ontarien du Cerveau)/ ; 0000045188//Ontario Brain Institute (Institut Ontarien du Cerveau)/ ; 0000045188//Ontario Brain Institute (Institut Ontarien du Cerveau)/ ; 0000045188//Ontario Brain Institute (Institut Ontarien du Cerveau)/ ; 0000045188//Ontario Brain Institute (Institut Ontarien du Cerveau)/ ; 0000045188//Ontario Brain Institute (Institut Ontarien du Cerveau)/ ; 0000045188//Ontario Brain Institute (Institut Ontarien du Cerveau)/ ; 0000045188//Ontario Brain Institute (Institut Ontarien du Cerveau)/ ; 0000045188//Ontario Brain Institute (Institut Ontarien du Cerveau)/ ; 0000045188//Ontario Brain Institute (Institut Ontarien du Cerveau)/ ; 0000045188//Ontario Brain Institute (Institut Ontarien du Cerveau)/ ; 0000045188//Ontario Brain Institute (Institut Ontarien du Cerveau)/ ; 0000045188//Ontario Brain Institute (Institut Ontarien du Cerveau)/ ; 0000045188//Ontario Brain Institute (Institut Ontarien du Cerveau)/ ; 0000045188//Ontario Brain Institute (Institut Ontarien du Cerveau)/ ; 0000045188//Ontario Brain Institute (Institut Ontarien du Cerveau)/ ; 0000045188//Ontario Brain Institute (Institut Ontarien du Cerveau)/ ; 0000045188//Ontario Brain Institute (Institut Ontarien du Cerveau)/ ; }, abstract = {Genetic factors contribute to neurodegenerative diseases, with high heritability estimates across diagnoses; however, a large portion of the genetic influence remains poorly understood. Many previous studies have attempted to fill the gaps by performing linkage analyses and association studies in individual disease cohorts, but have failed to consider the clinical and pathological overlap observed across neurodegenerative diseases and the potential for genetic overlap between the phenotypes. Here, we leveraged rare variant association analyses (RVAAs) to elucidate the genetic overlap among multiple neurodegenerative diagnoses, including Alzheimer's disease, amyotrophic lateral sclerosis, frontotemporal dementia (FTD), mild cognitive impairment, and Parkinson's disease (PD), as well as cerebrovascular disease, using the data generated with a custom-designed neurodegenerative disease gene panel in the Ontario Neurodegenerative Disease Research Initiative (ONDRI). As expected, only ~3% of ONDRI participants harboured a monogenic variant likely driving their disease presentation. Yet, when genes were binned based on previous disease associations, we observed an enrichment of putative loss of function variants in PD genes across all ONDRI cohorts. Further, individual gene-based RVAA identified significant enrichment of rare, nonsynonymous variants in PARK2 in the FTD cohort, and in NOTCH3 in the PD cohort. The results indicate that there may be greater heterogeneity in the genetic factors contributing to neurodegeneration than previously appreciated. Although the mechanisms by which these genes contribute to disease presentation must be further explored, we hypothesize they may be a result of rare variants of moderate phenotypic effect contributing to overlapping pathology and clinical features observed across neurodegenerative diagnoses.}, } @article {pmid34583710, year = {2021}, author = {Brown, J and Goodridge, D and Thorpe, L and Hodson, A and Chipanshi, M}, title = {Factors influencing practitioners' who do not participate in ethically complex, legally available care: scoping review.}, journal = {BMC medical ethics}, volume = {22}, number = {1}, pages = {134}, pmid = {34583710}, issn = {1472-6939}, mesh = {*Conscience ; Delivery of Health Care ; Health Facilities ; Humans ; *Physicians ; }, abstract = {BACKGROUND: Evolving medical technology, advancing biomedical and drug research, and changing laws and legislation impact patients' healthcare options and influence healthcare practitioners' (HCPs') practices. Conscientious objection policy confusion and variability can arise as it may occasionally be unclear what underpins non-participation. Our objective was to identify, analyze, and synthesize the factors that influenced HCPs who did not participate in ethically complex, legally available healthcare.

METHODS: We used Arksey and O'Malley's framework while considering Levac et al.'s enhancements, and qualitatively synthesized the evidence. We searched Medline, CINAHL, JSTOR, EMBASE, PsychINFO, Sociological Abstracts, and ProQuest Dissertations and Theses Global from January 1, 1998, to January 15, 2020, and reviewed the references of the final articles. We included articles written in English that discussed the factors that influenced physicians and registered nurses (RNs) who did not participate in end-of-life (EOL), reproductive technology and health, genetic testing, and organ or tissue donation healthcare areas. Using Covidence, we conducted title and abstract screening, followed by full-text screening against our eligibility criteria. We extracted the article's data into a spreadsheet, analyzed the articles, and completed a qualitative content analysis using NVivo12.

RESULTS: We identified 10,664 articles through the search, and after the screening, 16 articles were included. The articles sampled RNs (n = 5) and physicians (n = 11) and encompassed qualitative (n = 7), quantitative (n = 7), and mixed (n = 2) methodologies. The care areas included reproductive technology and health (n = 11), EOL (n = 3), organ procurement (n = 1), and genetic testing (n = 1). One article included two care areas; EOL and reproductive health. The themed factors that influenced HCPs who did not participate in healthcare were: (1) HCPs' characteristics, (2) personal beliefs, (3) professional ethos, 4) emotional labour considerations, and (5) system and clinical practice considerations.

CONCLUSION: The factors that influenced HCPs' who did not participate in ethically complex, legally available care are diverse. There is a need to recognize conscientious objection to healthcare as a separate construct from non-participation in healthcare for reasons other than conscience. Understanding these separate constructs will support HCPs' specific to the underlying factors influencing their practice participation.}, } @article {pmid34577245, year = {2021}, author = {Kwon, D and Park, Y and Park, Y}, title = {Provably Secure Three-Factor-Based Mutual Authentication Scheme with PUF for Wireless Medical Sensor Networks.}, journal = {Sensors (Basel, Switzerland)}, volume = {21}, number = {18}, pages = {}, pmid = {34577245}, issn = {1424-8220}, mesh = {Biometry ; *Computer Security ; Computer Simulation ; Confidentiality ; Humans ; *Telemedicine ; }, abstract = {Wireless medical sensor networks (WMSNs) are used in remote medical service environments to provide patients with convenient healthcare services. In a WMSN environment, patients wear a device that collects their health information and transmits the information via a gateway. Then, doctors make a diagnosis regarding the patient, utilizing the health information. However, this information can be vulnerable to various security attacks because the information is exchanged via an insecure channel. Therefore, a secure authentication scheme is necessary for WMSNs. In 2021, Masud et al. proposed a lightweight and anonymity-preserving user authentication scheme for healthcare environments. We discover that Masud et al.'s scheme is insecure against offline password guessing, user impersonation, and privileged insider attacks. Furthermore, we find that Masud et al.'s scheme cannot ensure user anonymity. To address the security vulnerabilities of Masud et al.'s scheme, we propose a three-factor-based mutual authentication scheme with a physical unclonable function (PUF). The proposed scheme is secure against various security attacks and provides anonymity, perfect forward secrecy, and mutual authentication utilizing biometrics and PUF. To prove the security features of our scheme, we analyze the scheme using informal analysis, Burrows-Abadi-Needham (BAN) logic, the Real-or-Random (RoR) model, and Automated Verification of Internet Security Protocols and Applications (AVISPA) simulation. Furthermore, we estimate our scheme's security features, computation costs, communication costs, and energy consumption compared with the other related schemes. Consequently, we demonstrate that our scheme is suitable for WMSNs.}, } @article {pmid34559807, year = {2021}, author = {Ciria, LF and Quintero, MJ and López, FJ and Luque, D and Cobos, PL and Morís, J}, title = {Intolerance of uncertainty and decisions about delayed, probabilistic rewards: A replication and extension of Luhmann, C. C., Ishida, K., & Hajcak, G. (2011).}, journal = {PloS one}, volume = {16}, number = {9}, pages = {e0256210}, pmid = {34559807}, issn = {1932-6203}, mesh = {*Anticipation, Psychological ; Anxiety/*psychology ; *Decision Making ; Female ; Humans ; Impulsive Behavior/*physiology ; Individuality ; Male ; Personality ; *Psychomotor Performance ; *Reward ; Risk-Taking ; *Uncertainty ; }, abstract = {Intolerance of Uncertainty (IU) is thought to lead to maladaptive behaviours and dysfunctional decision making, both in the clinical and healthy population. The seminal study reported by Luhmann and collaborators in 2011 [1] showed that IU was negatively associated with choosing a delayed, but more probable and valuable, reward over choosing an immediate, but less probable and valuable, reward. These findings have been widely disseminated across the field of personality and individual differences because of their relevance for the understanding of the role of IU in the development and maintenance of anxiety-related disorders. Given their importance it would be desirable to have replications of this study, but none have been carried out so far. The current study has been designed to replicate and extend Luhmann et al.'s results. Our sample will include 266 healthy participants (more than five times the sample size used by Luhmann et al.) to detect with a power of 95% the effect size that can be detected with a power of 33% in the original study. To increase our chances of getting such a sample size, the experiment will be conducted online, To increase our chances of getting such a sample size, the experiment will be conducted online, adding check trials to the original decision-making task to monitor participants' engagement. Additionally, we will explore the role of impulsivity in the relationship between IU and willingness to wait. This study will add empirical evidence about the role of IU in decision making and, in case of replication of Luhmann et al.'s results, will support the hypothesis that high-IU individuals may engage in inefficient or costly behaviour in exchange for less time enduring an uncertain situation.}, } @article {pmid34555993, year = {2023}, author = {Jiang, S and Wang, P and Liu, PL and Ngien, A and Wu, X}, title = {Social Media Communication about HPV Vaccine in China: A Study Using Topic Modeling and Survey.}, journal = {Health communication}, volume = {38}, number = {5}, pages = {935-946}, doi = {10.1080/10410236.2021.1983338}, pmid = {34555993}, issn = {1532-7027}, mesh = {Humans ; *Papillomavirus Vaccines ; *Social Media ; *Papillomavirus Infections/prevention & control ; Vaccination ; Information Seeking Behavior ; China ; Health Knowledge, Attitudes, Practice ; }, abstract = {The human papillomavirus (HPV) vaccine is relatively novel to people in China. Social media is becoming an important channel for learning new health information. However, limited is known about what HPV vaccine information has been disseminated on social media, and how such online information is associated with health-related behaviors in China. Based on Longo et al.'s model of patient use of healthcare information for healthcare decision, and Longo's model of health information seeking behaviors, this study examined HPV vaccine-related information type and information acquisition pattern. Following the mixed-methods approach, we first crawled 67,773 postings about HPV vaccine on Weibo, the largest microblogging website in China, and performed topic modeling to identify HPV vaccine-related topics that are prevalent on Weibo. The results showed six major topics about HPV vaccine, namely policy, guidance information, advertising, scandals, personal experience sharing, and HPV risks. Second, we conducted an online survey (n = 1,982) to investigate how scanning, seeking, and discussing the six HPV vaccine topics identified from big data analytics can affect HPV vaccine knowledge, safety concern, and vaccination intention. We documented significant impacts of social media health communication on users' health knowledge, attitude and behavioral intention.}, } @article {pmid34546276, year = {2021}, author = {Li, P and Lu, J and Wang, WY and Sui, X and Zou, C and Zhang, Y and Wang, J and Lin, D and Lu, Z and Song, H and Fan, X and Hao, J and Li, J and Liu, W}, title = {Lattice distortion-enhanced superlubricity of (Mo, X)S2 (X = Al, Ti, Cr and V) with moiré superlattice.}, journal = {Nanoscale}, volume = {13}, number = {38}, pages = {16234-16243}, doi = {10.1039/d1nr02382a}, pmid = {34546276}, issn = {2040-3372}, abstract = {Two-dimensional (2D) materials with the advantage of low interlayer shear strain are ultilized as lubricants in aerospace and precision manufacturing. Moiré superlattices (MSL), with attractive physical properties of electronic structures, interlayer hybridization and atomic forces, have been widely investigated in superlubricity, which is caused by elimination of interlayer lock-in by incommensurate atomic reconstruction. Although the foundations of superlubricity and the development of 2D lubricants via vanishing friction have been investigated, it is still important to comprehensively reveal the influence of MSL on the interlayer van der Waals (vdW) interactions of 2D lubricants. Here, the contributions of lattice distortions of solute-doped twisted bilayers (Mo, X)S2 (X = Al, Ti, V and Cr) to superlubricity are comprehensively investigated by high-throughput modelling and DFT-D2 calculations. It is revealed that the lattice distortion not only breaks the interlayer balance of repulsion and van der Waals interactions but also yields layer corrugation. These layer-corrugation-induced changes of the interlayer interactions and spacing distances are utilized to optimize lubricity, which matches with the experimental friction coefficients in the order of (Mo, Al)S2 > (Mo, Cr)S2 > MoS2 >(Mo, V)S2 >(Mo, Ti)S2. The evolutions of the band structures show an exponential relationship of the band edge width and layer deformations, paving a path to accelerate the development of advanced superlubricity materials via lattice distortions.}, } @article {pmid34545808, year = {2021}, author = {Garcia, DM and Campbell, EA and Jakobson, CM and Tsuchiya, M and Shaw, EA and DiNardo, AL and Kaeberlein, M and Jarosz, DF}, title = {A prion accelerates proliferation at the expense of lifespan.}, journal = {eLife}, volume = {10}, number = {}, pages = {}, pmid = {34545808}, issn = {2050-084X}, support = {R01 AG063418/AG/NIA NIH HHS/United States ; F32 GM109680/GM/NIGMS NIH HHS/United States ; F32 GM125162/GM/NIGMS NIH HHS/United States ; DP2 GM119140/GM/NIGMS NIH HHS/United States ; P30 AG013280/AG/NIA NIH HHS/United States ; RF1 AG057334/AG/NIA NIH HHS/United States ; }, mesh = {Cell Enlargement ; *Cell Proliferation ; Epigenesis, Genetic ; Gene Expression Regulation, Enzymologic ; Gene Expression Regulation, Fungal ; HSP70 Heat-Shock Proteins/genetics/metabolism ; Intramolecular Transferases/genetics/*metabolism ; Longevity ; *Meiosis ; Prion Proteins/genetics/*metabolism ; Protein Biosynthesis ; Saccharomyces cerevisiae/*enzymology/genetics/growth & development ; Saccharomyces cerevisiae Proteins/genetics/*metabolism ; Time Factors ; }, abstract = {In fluctuating environments, switching between different growth strategies, such as those affecting cell size and proliferation, can be advantageous to an organism. Trade-offs arise, however. Mechanisms that aberrantly increase cell size or proliferation-such as mutations or chemicals that interfere with growth regulatory pathways-can also shorten lifespan. Here we report a natural example of how the interplay between growth and lifespan can be epigenetically controlled. We find that a highly conserved RNA-modifying enzyme, the pseudouridine synthase Pus4/TruB, can act as a prion, endowing yeast with greater proliferation rates at the cost of a shortened lifespan. Cells harboring the prion grow larger and exhibit altered protein synthesis. This epigenetic state, [BIG[+]] (better in growth), allows cells to heritably yet reversibly alter their translational program, leading to the differential synthesis of dozens of proteins, including many that regulate proliferation and aging. Our data reveal a new role for prion-based control of an RNA-modifying enzyme in driving heritable epigenetic states that transform cell growth and survival.}, } @article {pmid34543804, year = {2022}, author = {O'Brien, B and Kane, L and Houle, SA and Aquilina, F and Ashbaugh, AR}, title = {Recall, response bias and recognition are differentially impacted by social anxiety irrespective of feedback modality.}, journal = {Journal of behavior therapy and experimental psychiatry}, volume = {74}, number = {}, pages = {101694}, doi = {10.1016/j.jbtep.2021.101694}, pmid = {34543804}, issn = {1873-7943}, mesh = {Anxiety ; Feedback ; Humans ; *Mental Recall ; Recognition, Psychology ; *Speech ; }, abstract = {BACKGROUND AND OBJECTIVES: This study replicates and extends Houle-Johnson et al.'s (2019) findings to better understand the role of feedback modality, ambiguity and social anxiety in the recognition and recall of self-relevant feedback.

METHODS: Participants gave a speech and were provided with positive, negative, and ambiguous feedback via written text, (n = 33) or recorded sentences (n = 31) and later completed a recognition and recall task for the feedback.

RESULTS: Recognition (p = .80, ηp[2] = 0) and recall (p = .09, ηp[2] = 0.08) did not differ between written or recorded feedback. All participants demonstrated a negative response bias (p < .001, ηp[2] = 0.22) and recalled more negative than positive feedback (p = .02, ηp[2] = 0.10) but were no more accurate in recognizing negative compared to positive feedback (p = .08, ηp[2] = 0). Although social anxiety did not impact recognition accuracy (p = .94, ηp[2] = 0), participants with high social anxiety demonstrated a more pronounced negative response bias (p < .01, ηp[2] = 0.11) and negative recall bias (p = .02, SE = 1.12) than low social anxiety participants. Moreover, the more negatively ambiguous items were perceived, the more likely they were identified old in the high social anxiety group, whereas the opposite was true for the low social anxiety group (B = .13, p < .10).

LIMITATIONS: Task believability was relatively low across all participants.

CONCLUSIONS: Our findings suggest that modality does not influence memory for feedback. Moreover, social anxiety might be characterized by a negative bias in recall and response bias, but not necessarily increased accuracy in recognition of negative feedback.}, } @article {pmid34542147, year = {2022}, author = {Zhang, X and Tang, L}, title = {Cultural adaptation in HPV vaccine intervention among racial and ethical minority population: a systematic literature review.}, journal = {Health education research}, volume = {36}, number = {5}, pages = {479-493}, doi = {10.1093/her/cyab034}, pmid = {34542147}, issn = {1465-3648}, mesh = {Cultural Characteristics ; Ethnicity ; Health Knowledge, Attitudes, Practice ; Humans ; Minority Groups ; *Papillomavirus Infections/prevention & control ; *Papillomavirus Vaccines ; Racial Groups ; United States ; Vaccination ; }, abstract = {Racial and ethnic minorities in the United States face higher risks of human papillomavirus (HPV) and are less likely to benefit from HPV vaccines. Effective HPV vaccine promotion efforts need to acknowledge and adapt to the cultural characteristics of these minority groups. This systematic review examines and evaluates the cultural adaptations in the HPV vaccine intervention studies conducted in racial and ethnic minority communities in the United States. We searched five databases and identified 26 peer-reviewed English-language journal articles published between 2010 and 2019. These articles were analyzed using Healey et al.'s (2017) cultural adaptation framework for community health interventions. Almost all of these interventions involved some cultural adaptation. However, there is a lack of use of theories in guiding intervention design, lack of systematic, planned cultural adaptations and insufficient in-depth understanding of the targeted population's cultural characteristics associated with their HPV-related attitudes, beliefs and behaviors. Future intervention studies should identify specific cultural characteristics related to vaccine attitudes and behaviors to create more targeted cultural adaptations in HPV vaccine promotion.}, } @article {pmid34536404, year = {2021}, author = {Cudkowicz, M and Genge, A and Maragakis, N and Petri, S and van den Berg, L and Aho, VV and Sarapohja, T and Kuoppamäki, M and Garratt, C and Al-Chalabi, A and , }, title = {Safety and efficacy of oral levosimendan in people with amyotrophic lateral sclerosis (the REFALS study): a randomised, double-blind, placebo-controlled phase 3 trial.}, journal = {The Lancet. Neurology}, volume = {20}, number = {10}, pages = {821-831}, doi = {10.1016/S1474-4422(21)00242-8}, pmid = {34536404}, issn = {1474-4465}, mesh = {Administration, Oral ; *Amyotrophic Lateral Sclerosis/drug therapy ; Double-Blind Method ; Humans ; Simendan/therapeutic use ; Treatment Outcome ; }, abstract = {BACKGROUND: There is an urgent unmet need for new therapies in amyotrophic lateral sclerosis. In a clinical study with healthy volunteers, levosimendan, a calcium sensitiser, was shown to improve neuromechanical efficiency and contractile function of the human diaphragm. We aimed to evaluate the safety and efficacy of oral levosimendan in people with amyotrophic lateral sclerosis, with a focus on respiratory function.

METHODS: The REFALS study is a randomised, double-blind, placebo-controlled phase 3 trial at 99 amyotrophic lateral sclerosis specialist centres in 14 countries worldwide. People with amyotrophic lateral sclerosis were eligible for participation if they were at least 18 years of age and had a sitting slow vital capacity (SVC) of 60-90% predicted. Participants were randomly assigned (2:1) by interactive web-response system to receive either levosimendan or placebo. The capsules for oral administration were identical in appearance to maintain blinding of participants and investigators. The primary endpoint was the change from baseline in supine SVC at 12 weeks, assessed as the percentage of predicted normal sitting SVC. The key secondary endpoint was the combined assessment of function and survival (CAFS) up to 48 weeks. Analyses were done in the intention-to-treat population, comprising all participants who were randomly assigned. This trial is registered at ClinicalTrials.gov (NCT03505021) and has been completed. An extension study (REFALS-ES; NCT03948178) has also been completed, but will be reported separately.

FINDINGS: Between June 21, 2018, and June 28, 2019, 871 people were screened for the study, of whom 496 were randomly assigned either levosimendan (n=329) or placebo (n=167). Participants were followed up between June 27, 2018 and June 26, 2020, for a median duration of 50·1 (IQR 37·5-51·1) weeks. The median duration of treatment was 47·9 (IQR 26·4-48·1) weeks. Change from baseline in supine SVC at 12 weeks was -6·73% with levosimendan and -6·99% with placebo, with no significant difference between the treatments (estimated treatment difference 0·26%, 95% CI -2·03 to 2·55, p=0·83). Similarly, at week 48, CAFS did not differ between treatment groups (least squares mean change from baseline 10·69, 95% CI -15·74 to 37·12; nominal p value=0·43). The most frequent adverse events were increased heart rate (106 [33%] of 326 receiving levosimendan vs 12 [7%] of 166 receiving placebo), fall (85 [26%] vs 48 [29%]), headache (93 [29%] vs 36 [22%]), and dyspnoea (59 [18%] vs 32 [19%]). 33 (10%) participants allocated levosimendan and 20 (12%) assigned placebo died during the trial, mainly due to respiratory failure or progression of amyotrophic lateral sclerosis.

INTERPRETATION: Levosimendan was not superior to placebo in maintaining respiratory function in a broad population with amyotrophic lateral sclerosis. Although levosimendan was generally well tolerated, increased heart rate and headache occurred more frequently with levosimendan than with placebo. The possibility of a clinically relevant subgroup of responsive individuals requires further evaluation.

FUNDING: Orion Corporation.}, } @article {pmid34536261, year = {2021}, author = {Chen, L and Yang, Y}, title = {Response to Comment on 'Soil carbon persistence governed by plant input and mineral protection at regional and global scales'.}, journal = {Ecology letters}, volume = {24}, number = {11}, pages = {2529-2532}, doi = {10.1111/ele.13883}, pmid = {34536261}, issn = {1461-0248}, support = {31770557//National Natural Science Foundation of China/ ; 31922054//National Natural Science Foundation of China/ ; 31825006//National Natural Science Foundation of China/ ; 31988102//National Natural Science Foundation of China/ ; }, mesh = {*Carbon ; Minerals ; Plants ; *Soil ; }, abstract = {We demonstrated that ignoring the non-linear relationship between topsoil Δ[14] C and plant carbon (C) input in Wu et al.'s analysis was the fundamental reason for the discrepancy between their analysis and ours. By considering such a non-linear relationship, plant C input still predominantly governs the topsoil C turnover.}, } @article {pmid34520345, year = {2021}, author = {Spalla, D and Cornacchia, IM and Treves, A}, title = {Continuous attractors for dynamic memories.}, journal = {eLife}, volume = {10}, number = {}, pages = {}, pmid = {34520345}, issn = {2050-084X}, mesh = {*Memory, Episodic ; *Models, Biological ; *Neural Networks, Computer ; }, abstract = {Episodic memory has a dynamic nature: when we recall past episodes, we retrieve not only their content, but also their temporal structure. The phenomenon of replay, in the hippocampus of mammals, offers a remarkable example of this temporal dynamics. However, most quantitative models of memory treat memories as static configurations, neglecting the temporal unfolding of the retrieval process. Here, we introduce a continuous attractor network model with a memory-dependent asymmetric component in the synaptic connectivity, which spontaneously breaks the equilibrium of the memory configurations and produces dynamic retrieval. The detailed analysis of the model with analytical calculations and numerical simulations shows that it can robustly retrieve multiple dynamical memories, and that this feature is largely independent of the details of its implementation. By calculating the storage capacity, we show that the dynamic component does not impair memory capacity, and can even enhance it in certain regimes.}, } @article {pmid34506565, year = {2021}, author = {Cahyadi, EF and Hwang, MS}, title = {An improved efficient anonymous authentication with conditional privacy-preserving scheme for VANETs.}, journal = {PloS one}, volume = {16}, number = {9}, pages = {e0257044}, pmid = {34506565}, issn = {1932-6203}, mesh = {*Automobiles ; *Computer Communication Networks ; Computer Security ; *Privacy ; }, abstract = {The study of security and privacy in vehicular ad hoc networks (VANETs) has become a hot topic that is wide open to discussion. As the quintessence of this aspect, authentication schemes deployed in VANETs play a substantial role in providing secure communication among vehicles and the surrounding infrastructures. Many researchers have proposed a variety of schemes related to information verification and computation efficiency in VANETs. In 2018, Kazemi et al. proposed an evaluation and improvement work towards Azees et al.'s efficient anonymous authentication with conditional privacy-preserving (EAAP) scheme for VANETs. They claimed that the EAAP suffered from replaying attacks, impersonation attacks, modification attacks, and cannot provide unlinkability. However, we also found out if Kazemi et al.'s scheme suffered from the unlinkability issue that leads to a forgery attack. An adversary can link two or more messages sent by the same user by applying Euclid's algorithm and derives the user's authentication key. To remedy the issue, in this paper, we proposed an improvement by encrypting the message using a shared secret key between sender and receiver and apply a Nonce in the final message to guarantee the unlinkability between disseminated messages.}, } @article {pmid34505574, year = {2021}, author = {Venz, R and Pekec, T and Katic, I and Ciosk, R and Ewald, CY}, title = {End-of-life targeted degradation of DAF-2 insulin/IGF-1 receptor promotes longevity free from growth-related pathologies.}, journal = {eLife}, volume = {10}, number = {}, pages = {}, pmid = {34505574}, issn = {2050-084X}, support = {P40 OD010440/OD/NIH HHS/United States ; }, mesh = {Animals ; Caenorhabditis elegans/*genetics/growth & development/*physiology ; Caenorhabditis elegans Proteins/genetics/*metabolism ; Longevity/*genetics ; Mutation ; Phenotype ; Receptor, IGF Type 1/genetics/*metabolism ; Receptor, Insulin/*genetics/*metabolism ; Signal Transduction/genetics ; }, abstract = {Preferably, lifespan-extending therapies should work when applied late in life without causing undesired pathologies. Reducing insulin/insulin-like growth factor (IGF)-1 signaling (IIS) increases lifespan across species, but the effects of reduced IIS interventions in extreme geriatric ages remains unknown. Using the nematode Caenorhabditis elegans, we engineered the conditional depletion of the DAF-2/insulin/IGF-1 transmembrane receptor using an auxin-inducible degradation (AID) system. This allowed for the temporal and spatial reduction in DAF-2 protein levels at time points after which interventions such as RNAi become ineffective. Using this system, we found that AID-mediated depletion of DAF-2 protein surpasses the longevity of daf-2 mutants. Depletion of DAF-2 during early adulthood resulted in multiple adverse phenotypes, including growth retardation, germline shrinkage, egg retention, and reduced brood size. By contrast, AID-mediated depletion of DAF-2 post-reproduction, or specifically in the intestine in early adulthood, resulted in an extension of lifespan without these deleterious effects. Strikingly, at geriatric ages, when 75% of the population had died, AID-mediated depletion of DAF-2 protein resulted in a doubling in lifespan. Thus, we provide a proof-of-concept that even close to the end of an individual's lifespan, it is possible to slow aging and promote longevity.}, } @article {pmid34499387, year = {2021}, author = {Oliviero, G and Ruggiero, L and D'Antonio, E and Gagliardi, M and Nunziata, R and Di Sarno, A and Abbatiello, C and Di Feo, E and De Vivo, S and Santonicola, A and Iovino, P}, title = {Replay to Response to Oliviero et al.'s Publication: "Impact of COVID-19 lockdown on symptoms in patients with functional gastrointestinal disorders: Relationship with anxiety and perceived stress".}, journal = {Neurogastroenterology and motility}, volume = {33}, number = {11}, pages = {e14263}, pmid = {34499387}, issn = {1365-2982}, mesh = {Anxiety ; *COVID-19 ; Communicable Disease Control ; Depression ; *Gastrointestinal Diseases ; Humans ; SARS-CoV-2 ; Stress, Psychological ; }, } @article {pmid34498518, year = {2021}, author = {Williams, MT and Skinta, MD and Martin-Willett, R}, title = {After Pierce and Sue: A Revised Racial Microaggressions Taxonomy.}, journal = {Perspectives on psychological science : a journal of the Association for Psychological Science}, volume = {16}, number = {5}, pages = {991-1007}, doi = {10.1177/1745691621994247}, pmid = {34498518}, issn = {1745-6924}, mesh = {*Aggression ; Humans ; Microaggression ; Racial Groups ; *Racism ; }, abstract = {Harvard psychiatrist Chester Pierce's conception of "subtle and stunning" daily racial offenses, or microaggressions, remains salient even 50 years after it was introduced. Microaggressions were defined further by Sue and colleagues in 2007, and this construct has found growing utility as the deleterious effects of microaggressions on the health of people of color continues to mount. Many studies seek to frame microaggressions in terms of a taxonomic analysis of offender behavior to inform the assessment of and interventions for the reduction of racial microaggressions. This article proposes an expansion and refinement of Sue et al.'s taxonomy to better inform such efforts. We conducted a review of published articles that focused on qualitative and quantitative findings of microaggressions taxonomies (N = 32). Sixteen categories of racial microaggressions were identified, largely consistent with the original taxonomy of Sue et al. but expanded in several notable ways. Building on our prior research, other researchers supported such new categories as tokenism, connecting via stereotypes, exoticization and eroticization, and avoidance and distancing. The least studied categories included the denial of individual racism from Sue et al., and newer categories included reverse-racism hostility, connecting via stereotypes, and environmental attacks. A unified language of microaggressions may improve understanding and measurement of this important construct.}, } @article {pmid34495812, year = {2022}, author = {Link, JS and Lu, LH and Armistead-Jehle, P and Seegmiller, RA}, title = {Validation of grooved pegboard cutoffs as an additional embedded measure of performance validity.}, journal = {The Clinical neuropsychologist}, volume = {36}, number = {8}, pages = {2331-2341}, doi = {10.1080/13854046.2021.1942556}, pmid = {34495812}, issn = {1744-4144}, mesh = {Male ; Humans ; Female ; Neuropsychological Tests ; Reproducibility of Results ; *Malingering/diagnosis ; }, abstract = {OBJECTIVE: Using embedded performance validity (PVT) comparisons, Erdodi et al. suggested that Grooved Pegboard (GPB) T-score cutoffs for either hand (≤ 29) or both hands (≤ 31) could be used as additional embedded PVTs. The current study evaluated the relationship between these proposed cutoff scores and established PVTs (Medical Symptom Validity Test [MSVT]; Non-Verbal Medical Symptom Validity Test [NV-MSVT], and Reliable Digit Span [RDS]).

METHOD: Participants (N = 178) were predominately Caucasian (84%) males (79%) with a mean age and education of 41 (SD = 11.7) and 15.8 years (SD = 2.3), respectively. Participants were stratified as "passing" or "failing" the GPBviaErdodi's proposed criteria. "Failures" on the MSVT, NV-MSVT, and RDS were based on conventional recommendations.

RESULTS: Moderate correlations between GPB classification and a condition of interest (COI; i.e. at least two failures on reference PVTs) were observed for dominant (χ[2] (1, n = 178) = 34.72, ϕ = .44, p < .001), non-dominant (χ[2] (1, n = 178) = 16.46, ϕ = .30, p = .001), and both hand conditions (χ[2] (1, n = 178) = 32.48, ϕ = .43, p < .001). Sensitivity, specificity, and predictive power were generally higher than Erdodi et al.'s initial findings.

CONCLUSION: These findingsprovide supportfor the clinical utility of the GPB as an additional embedded PVT. More specifically, dominant and both hand cutoffs were found to be more robust measures ofnon-genuine performance in those without motor deficits. While promising, sensitivity continues to be low; therefore, it is ill-advised to use the GPB as a sole measure of -performance validity.}, } @article {pmid34493944, year = {2021}, author = {Diego-Mantecon, JM and Prodromou, T and Lavicza, Z and Blanco, TF and Ortiz-Laso, Z}, title = {An attempt to evaluate STEAM project-based instruction from a school mathematics perspective.}, journal = {ZDM : the international journal on mathematics education}, volume = {53}, number = {5}, pages = {1137-1148}, pmid = {34493944}, issn = {1863-9690}, abstract = {Official documents in several educational systems reflect the importance of integrating Science, Technology, Engineering, Arts, and Mathematics (STEAM) and consider project-based learning (PBL) as a way of integrating such disciplines in the classroom. Although STEAM-PBL has been characterized and evaluated in different ways, its impact on school mathematics teaching remains unclear. Mathematics is recognized as the fundamental basis of other disciplines; however, many students still perceive it as a difficult subject and abandon it. To analyze STEAM-PBL classroom implementation from a school mathematics standpoint, we examined 41 classroom experiences from 11 Spanish secondary education teachers (five in-field mathematics teachers), who participated in a STEAM training program for more than 4 years. To frame this study, Thibaut et al.'s (J STEM Educ 3(1):02, 2018) and Schoenfeld's (Educ Res 43(8):404-412, 2014) characterizations of well-designed and implemented projects, respectively, were employed. The results showed that in-field mathematics teachers avoided transdisciplinary projects in which school mathematics is difficult to address, while out-of-field teachers tended to overlook the mathematics in interdisciplinary projects. Unlike out-of-field teachers, mathematics teachers often eluded design-based learning processes for deeply exploiting school mathematics. The latter teachers promoted high cognitive demands and positive perceptions about mathematics in projects where formative environments were generated through discussion and a meaningful feedback loop.}, } @article {pmid34493422, year = {2022}, author = {Bowers, C and Randawa, A and Sloan, B and Anwar, U and Phipps, A and Muthayya, P}, title = {Enzymatic debridement in critically injured burn patients - Our experience in the intensive care setting and during burn resuscitation.}, journal = {Burns : journal of the International Society for Burn Injuries}, volume = {48}, number = {4}, pages = {846-859}, doi = {10.1016/j.burns.2021.07.023}, pmid = {34493422}, issn = {1879-1409}, mesh = {Adult ; *Bromelains/therapeutic use ; *Burns/surgery ; Critical Care ; Debridement/methods ; Humans ; Retrospective Studies ; Wound Healing ; }, abstract = {BACKGROUND: Much of the recent literature on bromelain based enzymatic debridement of burn injury has focused on its use in smaller burn injury and specialist areas such as the hands or genitals (Krieger et al., 2012; Schulz et al., 2017a,b,c,d). This is despite the original papers describing its use in larger burn injury (Rosenberg et al., 2004, 2014). The current EMA license for Nexobrid™ advises that it should not be used for burn injuries of more than 15% TBSA and should be used with caution in patients with pulmonary burn trauma and suspected pulmonary burn trauma. The original safety and efficacy trial of NexoBrid™ limited its use to 15% TBSA aliquots with concern regarding the effect of bromelain on coagulation. In a European consensus paper of experienced burns clinicians, now on its second iteration, 100% of respondents agreed that "up to 30% BSA can be treated by enzymatic debridement based on individual decision" (Hirche et al., 2017). Hofmaenner et al.'s recent study on the safety of enzymatic debridement in extensive burns larger than 15% provides some further evidence that "bromelain based enzymatic debridement can be carried out safely in large-area burns" (Hofmaenner et al., 2020) but the literature is scant in these larger debridement areas. In our centre we have been using enzymatic debridement for resuscitation level burn injury since 2016. We have gained significant learning in this time; this article aims to describe our current protocol for enzymatic debridement in this patient population and highlight specific learning points that might aid other centres in using enzymatic debridement for larger burn injury.

METHOD: We performed a search of the IBID database to identify all adult patients who satisfied the inclusion criteria of resuscitation level burn injury (defined as total burn surface area (TBSA) ≥15% in patients aged >16 years), or level 3 admission following burn injury and who underwent Enzymatic Debridement. A case note review was completed, and details comprising patient demographics, TBSA, mechanism of burn, presence of inhalation injury, sequencing of debridement, length of ICU and hospital stay, blood product utilisation and the need for autografting were recorded. No ethical approval has been sought for this retrospective review.

RESULTS: We identified 29 patients satisfying the inclusion criteria (Table 1). Between June 2016 and June 2020 the average total burn size of patients who had at least some of their burn treated by enzymatic debridement increased from 21.4% in 2016/17 to 34.7% in 2019/20. In these patients the actual area treated by enzymatic debridement also increased from 11.9% TBSA to 20.3% TBSA. 19 patients (66%) had enzymatic debridement performed within 24 h of injury, a further 2 patients (7%) within 48 h after injury. Patients were more likely to have enzymatic debridement commenced in the first 24 h after injury if they had circumferential limb injury (39% vs 9%) or were planned for enzyme only debridement (78% vs 28%). Those who were planned for combination enzyme and surgical debridement were more likely to have enzymatic debridement commenced after the first 48 h (75%). We have performed enzymatic debridement overnight on one occasion, for a patient who presented with circumferential limb injury and was determined to undergo urgent debridement.

CONCLUSION: Much of the literature has described the use of enzymatic debridement in smaller burns, and specialist areas. However, it is our opinion that the advantages of enzymatic debridement appear to be greater in larger burns with a facility for whole burn excision on the day of admission in the ICU cubicle. We have demonstrated significantly reduced blood loss, improved dermal preservation, reduced need for autografting, and a reduction in the number of trips to theatre. We would advocate that both the team and the patient need to be as prepared as they would be for a traditional surgical excision. The early part of our learning curve for enzymatic debridement in resuscitation level injuries was steep, and we were able to build on experience from managing smaller injuries. We recommend any team wishing to using enzymatic debridement gain experience in the same way and develop robust local pathways prior to attempting use in larger burn injuries.}, } @article {pmid34491075, year = {2022}, author = {Mathieu, JE and Wolfson, MA and Park, S and Luciano, MM and Bedwell-Torres, WL and Ramsay, PS and Klock, EA and Tannenbaum, SI}, title = {Indexing dynamic collective constructs using computer-aided text analysis: Construct validity evidence and illustrations featuring team processes.}, journal = {The Journal of applied psychology}, volume = {107}, number = {4}, pages = {533-559}, doi = {10.1037/apl0000856}, pmid = {34491075}, issn = {1939-1854}, support = {//Army Research Institute/ ; /NASA/NASA/United States ; }, mesh = {*Computers ; Humans ; }, abstract = {Organizational processes have been widely recognized as both multilevel and dynamic, yet traditional methods of measurements limit our ability to model and understand such phenomena. Featuring a popular model of team processes advanced by Marks et al. (2001), we illustrate a method to use individuals' communications as construct valid unobtrusive measures of collective constructs occurring over time. Thus, the purpose of this investigation is to develop computer-aided text analysis (CATA) techniques that can score members' communications into valid team process measures. We apply a deductive content validity-based method to construct CATA dictionaries for Marks et al.'s dimensions. We then demonstrate their convergent validity with subject matter experts' (SMEs) hand-coded team communications and different SMEs' behaviorally anchored rating scales based on video recordings of team interactions, using multitrait-multimethod analyses in two samples. Using a third sample of paramedics performing a high-fidelity mass casualty incident exercise, we further demonstrate the convergent validity of the CATA and SME scorings of communications. We then model the relationships among processes across episodes using all three samples. Next, we test criterion-related validity using a longitudinal dual-discontinuous change growth modeling design featuring the paramedic CATA-scored team processes as related to a dynamic performance criterion. Finally, we integrate behavioral data from wearable sensor badges to illustrate how CATA can be scored at the individual level and then leveraged to model dynamic networks of team interactions. Implications, limitations, directions for the future research, and guidelines for the application of these techniques to other collective constructs are discussed. (PsycInfo Database Record (c) 2022 APA, all rights reserved).}, } @article {pmid34490911, year = {2021}, author = {Lowder, MW and Gordon, PC}, title = {Relative Clause Effects at the Matrix Verb Depend on Type of Intervening Material.}, journal = {Cognitive science}, volume = {45}, number = {9}, pages = {e13039}, doi = {10.1111/cogs.13039}, pmid = {34490911}, issn = {1551-6709}, mesh = {Causality ; *Comprehension ; Eye Movements ; Humans ; Language ; *Psycholinguistics ; }, abstract = {Although a large literature demonstrates that object-extracted relative clauses (ORCs) are harder to process than subject-extracted relative clauses (SRCs), there is less agreement regarding where during processing this difficulty emerges, as well as how best to explain these effects. An eye-tracking study by Staub, Dillon, and Clifton (2017) demonstrated that readers experience more processing difficulty at the matrix verb for ORCs than for SRCs when the matrix verb immediately follows the relative clause (RC), but the difficulty is eliminated if a prepositional phrase (PP) intervenes. A careful examination of Staub et al.'s materials reveals that the types of PPs used in the experiment were a mixture of locative and temporal PPs. This is important in that locative PPs can modify either a noun phrase or a verb phrase (VP), whereas temporal PPs typically modify VPs, resulting in systematic differences in PP attachment across ORCs versus SRCs. In the current eye-tracking experiment, we systematically manipulated RC type and PP type in the same sentences used by Staub et al. The manipulation of PP type resulted in a crossover pattern at the matrix verb such that there was a trend for reading times to be longer for ORCs than SRCs when the PP was locative, but reading times were longer for SRCs than ORCs when the PP was temporal. These results provide important information regarding the locus of RC-processing effects and highlight the importance of carefully considering how intervening material might unintentionally alter the structure or the meaning of a sentence.}, } @article {pmid34487362, year = {2022}, author = {Meier, R and Blaimer, BB and Buenaventura, E and Hartop, E and von Rintelen, T and Srivathsan, A and Yeo, D}, title = {A re-analysis of the data in Sharkey et al.'s (2021) minimalist revision reveals that BINs do not deserve names, but BOLD Systems needs a stronger commitment to open science.}, journal = {Cladistics : the international journal of the Willi Hennig Society}, volume = {38}, number = {2}, pages = {264-275}, doi = {10.1111/cla.12489}, pmid = {34487362}, issn = {1096-0031}, support = {R-154-000-A22-112//Ministry of Education/ ; }, abstract = {Halting biodiversity decline is one of the most critical challenges for humanity, but monitoring biodiversity is hampered by taxonomic impediments. One impediment is the large number of undescribed species (here called "dark taxon impediment") whereas another is caused by the large number of superficial species descriptions, that can only be resolved by consulting type specimens ("superficial description impediment"). Recently, Sharkey et al. (2021) proposed to address the dark taxon impediment for Costa Rican braconid wasps by describing 403 species based on COI barcode clusters ("BINs") computed by BOLD Systems. More than 99% of the BINs (387 of 390) were converted into species by assigning binominal names (e.g. BIN "BOLD:ACM9419" becomes Bracon federicomatarritai) and adding a minimal diagnosis (consisting only of a consensus barcode for most species). We here show that many of Sharkey et al.'s species are unstable when the underlying data are analyzed using different species delimitation algorithms. Add the insufficiently informative diagnoses, and many of these species will become the next "superficial description impediment" for braconid taxonomy because they will have to be tested and redescribed after obtaining sufficient evidence for confidently delimiting species. We furthermore show that Sharkey et al.'s approach of using consensus barcodes as diagnoses is not functional because it cannot be applied consistently. Lastly, we reiterate that COI alone is not suitable for delimiting and describing species, and voice concerns over Sharkey et al.'s uncritical use of BINs because they are calculated by a proprietary algorithm (RESL) that uses a mixture of public and private data. We urge authors, reviewers and editors to maintain high standards in taxonomy by only publishing new species that are rigorously delimited with open-access tools and supported by publicly available evidence.}, } @article {pmid34486522, year = {2021}, author = {Friedman, RZ and Granas, DM and Myers, CA and Corbo, JC and Cohen, BA and White, MA}, title = {Information content differentiates enhancers from silencers in mouse photoreceptors.}, journal = {eLife}, volume = {10}, number = {}, pages = {}, pmid = {34486522}, issn = {2050-084X}, support = {R01 EY030075/EY/NEI NIH HHS/United States ; R01 EY025196/EY/NEI NIH HHS/United States ; R01 GM121755/GM/NIGMS NIH HHS/United States ; F31 HG011431/HG/NHGRI NIH HHS/United States ; R01 EY027784/EY/NEI NIH HHS/United States ; }, mesh = {Animals ; Binding Sites ; Female ; Male ; Mice ; Photoreceptor Cells/*physiology ; Protein Binding ; Retina/cytology/physiology ; Transcription Factors/genetics/*metabolism ; }, abstract = {Enhancers and silencers often depend on the same transcription factors (TFs) and are conflated in genomic assays of TF binding or chromatin state. To identify sequence features that distinguish enhancers and silencers, we assayed massively parallel reporter libraries of genomic sequences targeted by the photoreceptor TF cone-rod homeobox (CRX) in mouse retinas. Both enhancers and silencers contain more TF motifs than inactive sequences, but relative to silencers, enhancers contain motifs from a more diverse collection of TFs. We developed a measure of information content that describes the number and diversity of motifs in a sequence and found that, while both enhancers and silencers depend on CRX motifs, enhancers have higher information content. The ability of information content to distinguish enhancers and silencers targeted by the same TF illustrates how motif context determines the activity of cis-regulatory sequences.}, } @article {pmid34478467, year = {2021}, author = {Ding, N and Frohnwieser, A and Miller, R and Clayton, NS}, title = {Waiting for the better reward: Comparison of delay of gratification in young children across two cultures.}, journal = {PloS one}, volume = {16}, number = {9}, pages = {e0256966}, pmid = {34478467}, issn = {1932-6203}, mesh = {Child, Preschool ; China ; *Delay Discounting ; Female ; Humans ; Male ; *Reward ; Self-Control/*psychology ; United Kingdom ; }, abstract = {Delay of gratification-a form of self-control-is the ability to forsake immediately available rewards in order to obtain larger-valued outcomes in future, which develops throughout the pre-school years. The majority of previous research in this area has been conducted with Western populations, therefore knowledge of Eastern children's performance is scarcer. Here, utilising on a recently published dataset of British children (n = 61), we further tested delay of gratification in 3 to 5-year-old Chinese children (n = 75) using Bramlett et al.'s (2012) delay choice paradigm. The paradigm was previously used in non-human primates and it featured a mechanized rotating tray that sequentially moves rewards within reach. Additionally, we administered 3 inhibitory control tasks and 1 standardised delay choice task to Chinese pre-schoolers (British children were not tested). We aimed to investigate the influence of culture, reward type and reward visibility on pre-schoolers' ability to delay gratification. We found significant age-related improvements in delay of gratification ability in both countries and children performed better when presented with rewards varying in quality than quantity. Consistent with previous cross-cultural literature, Chinese children showed better overall performance than their British peers when reward visibility was manipulated (though reward visibility itself had no significant effect on performance). There were significant correlations in Chinese children's performance in Bramlett et al.'s (2012) delay choice paradigm and performance in some (though not all tested) inhibitory control tasks. We discuss these results in relation to task demands and the broader social orientation of self-control. We concluded that the intuitive comparative assessment of self-control task taps into children's delay of gratification ability. Our results emphasize the importance of testing for socio-cultural influences on children's cognitive development.}, } @article {pmid34473059, year = {2021}, author = {Roussel, Y and Gaudreau, SF and Kacer, ER and Sengupta, M and Bui, TV}, title = {Modeling spinal locomotor circuits for movements in developing zebrafish.}, journal = {eLife}, volume = {10}, number = {}, pages = {}, pmid = {34473059}, issn = {2050-084X}, mesh = {Animals ; Locomotion/*physiology ; *Models, Biological ; Motor Activity/physiology ; Motor Neurons/physiology ; Nerve Net/*physiology ; Neurons/physiology ; Spinal Cord/*physiology ; Swimming/physiology ; Zebrafish/*growth & development/*physiology ; }, abstract = {Many spinal circuits dedicated to locomotor control have been identified in the developing zebrafish. How these circuits operate together to generate the various swimming movements during development remains to be clarified. In this study, we iteratively built models of developing zebrafish spinal circuits coupled to simplified musculoskeletal models that reproduce coiling and swimming movements. The neurons of the models were based upon morphologically or genetically identified populations in the developing zebrafish spinal cord. We simulated intact spinal circuits as well as circuits with silenced neurons or altered synaptic transmission to better understand the role of specific spinal neurons. Analysis of firing patterns and phase relationships helped to identify possible mechanisms underlying the locomotor movements of developing zebrafish. Notably, our simulations demonstrated how the site and the operation of rhythm generation could transition between coiling and swimming. The simulations also underlined the importance of contralateral excitation to multiple tail beats. They allowed us to estimate the sensitivity of spinal locomotor networks to motor command amplitude, synaptic weights, length of ascending and descending axons, and firing behavior. These models will serve as valuable tools to test and further understand the operation of spinal circuits for locomotion.}, } @article {pmid34469639, year = {2021}, author = {Hesaraki, M and Akbarizadeh, M and Ahmadidarrehsima, S and Moghadam, MP and Izadpanah, F}, title = {Knowledge, attitude, practice and clinical recommendations of health care workers towards COVID-19: a systematic review.}, journal = {Reviews on environmental health}, volume = {36}, number = {3}, pages = {345-357}, doi = {10.1515/reveh-2020-0099}, pmid = {34469639}, issn = {2191-0308}, mesh = {*Attitude of Health Personnel ; COVID-19/*epidemiology ; Communication ; Cross-Sectional Studies ; *Health Knowledge, Attitudes, Practice ; Health Personnel/*psychology ; Humans ; Infection Control/standards ; Inservice Training ; SARS-CoV-2 ; }, abstract = {OBJECTIVES: This study aimed to evaluate the knowledge, attitude, practice, and clinical recommendations of health care workers (HCWs) towards COVID-19.

METHODS: In this systematic review study, international databases (Web of Science, PubMed, and Scopus) were searched for the relevant studies published in English from the inception of databases until July 30, 2020. Hoy et al.'s tool was used to evaluate the quality of studies. All search steps, screening, selection of studies, quality assessment, and data extraction were performed separately by two researchers.

RESULTS: Out of 3460 articles searched, 28 articles conducted on 16,427 HCWs were included in the study. Most of the HCWs had good knowledge (72.2%), a positive attitude (70.9%), and good practice (78.8%) towards COVID-19. The most important clinical recommendation to improve knowledge, attitude, and practice (KAP) was to provide HCWs with a periodic training program regarding COVID-19. The most important source of information for HCWs on COVID-19 was social networks.

CONCLUSIONS: Despite HCWs' good knowledge, attitude, and practice (KAP), it is recommended to periodically review KAP and carry out further studies in different countries as well. It is also recommended to use social media to improve KAP.}, } @article {pmid34469061, year = {2022}, author = {Chang, MC}, title = {Regarding Oh et al.'s "Ultrasound-guided pulsed radiofrequency of the saphenous nerve in a complex regional pain syndrome patient with lower limb pain".}, journal = {Pain practice : the official journal of World Institute of Pain}, volume = {22}, number = {2}, pages = {296}, doi = {10.1111/papr.13072}, pmid = {34469061}, issn = {1533-2500}, mesh = {*Complex Regional Pain Syndromes/therapy ; Humans ; Lower Extremity ; Pain ; *Pulsed Radiofrequency Treatment ; Ultrasonography, Interventional ; }, } @article {pmid34468950, year = {2021}, author = {Ash, GI and Stults-Kolehmainen, M and Busa, MA and Gaffey, AE and Angeloudis, K and Muniz-Pardos, B and Gregory, R and Huggins, RA and Redeker, NS and Weinzimer, SA and Grieco, LA and Lyden, K and Megally, E and Vogiatzis, I and Scher, L and Zhu, X and Baker, JS and Brandt, C and Businelle, MS and Fucito, LM and Griggs, S and Jarrin, R and Mortazavi, BJ and Prioleau, T and Roberts, W and Spanakis, EK and Nally, LM and Debruyne, A and Bachl, N and Pigozzi, F and Halabchi, F and Ramagole, DA and Janse van Rensburg, DC and Wolfarth, B and Fossati, C and Rozenstoka, S and Tanisawa, K and Börjesson, M and Casajus, JA and Gonzalez-Aguero, A and Zelenkova, I and Swart, J and Gursoy, G and Meyerson, W and Liu, J and Greenbaum, D and Pitsiladis, YP and Gerstein, MB}, title = {Establishing a Global Standard for Wearable Devices in Sport and Exercise Medicine: Perspectives from Academic and Industry Stakeholders.}, journal = {Sports medicine (Auckland, N.Z.)}, volume = {51}, number = {11}, pages = {2237-2250}, pmid = {34468950}, issn = {1179-2035}, support = {T35 HL007649/HL/NHLBI NIH HHS/United States ; R01 DA051906/DA/NIDA NIH HHS/United States ; R01 HL126770/HL/NHLBI NIH HHS/United States ; I01 CX001825/CX/CSRD VA/United States ; K99HG010909/NH/NIH HHS/United States ; U54 AA027989/AA/NIAAA NIH HHS/United States ; Fellowship//Office of Academic Affiliations, Department of Veterans Affairs/ ; K99 HG010909/HG/NHGRI NIH HHS/United States ; UL1 TR001863/TR/NCATS NIH HHS/United States ; K23 AA026890/AA/NIAAA NIH HHS/United States ; R00 NR018886/NR/NINR NIH HHS/United States ; K23AA026890/NH/NIH HHS/United States ; K12 DK094714/DK/NIDDK NIH HHS/United States ; #1I01CX001825//U.S. Department of Veterans Affairs/ ; K99 NR018886/NR/NINR NIH HHS/United States ; R01HL126770/NH/NIH HHS/United States ; K99NR018886/NH/NIH HHS/United States ; 220-BS-19//American Academy of Sleep Medicine/ ; }, mesh = {Consensus ; Exercise ; Humans ; *Sports ; *Sports Medicine ; *Wearable Electronic Devices ; }, abstract = {Millions of consumer sport and fitness wearables (CSFWs) are used worldwide, and millions of datapoints are generated by each device. Moreover, these numbers are rapidly growing, and they contain a heterogeneity of devices, data types, and contexts for data collection. Companies and consumers would benefit from guiding standards on device quality and data formats. To address this growing need, we convened a virtual panel of industry and academic stakeholders, and this manuscript summarizes the outcomes of the discussion. Our objectives were to identify (1) key facilitators of and barriers to participation by CSFW manufacturers in guiding standards and (2) stakeholder priorities. The venues were the Yale Center for Biomedical Data Science Digital Health Monthly Seminar Series (62 participants) and the New England Chapter of the American College of Sports Medicine Annual Meeting (59 participants). In the discussion, stakeholders outlined both facilitators of (e.g., commercial return on investment in device quality, lucrative research partnerships, and transparent and multilevel evaluation of device quality) and barriers (e.g., competitive advantage conflict, lack of flexibility in previously developed devices) to participation in guiding standards. There was general agreement to adopt Keadle et al.'s standard pathway for testing devices (i.e., benchtop, laboratory, field-based, implementation) without consensus on the prioritization of these steps. Overall, there was enthusiasm not to add prescriptive or regulatory steps, but instead create a networking hub that connects companies to consumers and researchers for flexible guidance navigating the heterogeneity, multi-tiered development, dynamicity, and nebulousness of the CSFW field.}, } @article {pmid34464937, year = {2021}, author = {Kikuta, S and Sakata, D and Fukuda, S}, title = {Computational modeling for the evaluation of suppressed scintillation yields in plastic scintillators using Geant4.}, journal = {Physica medica : PM : an international journal devoted to the applications of physics to medicine and biology : official journal of the Italian Association of Biomedical Physics (AIFB)}, volume = {89}, number = {}, pages = {258-264}, doi = {10.1016/j.ejmp.2021.08.005}, pmid = {34464937}, issn = {1724-191X}, mesh = {Linear Energy Transfer ; Monte Carlo Method ; Photons ; *Plastics ; *Scintillation Counting ; }, abstract = {The yield of scintillation photons emitted from scintillators is considered to be proportional to the LET (linear energy transfer) which is energy distribution per unit length, in the low-LET domain, but not proportional in the high LET domain due to the suppression yield from the so-called quenching effect. Ogawa et al. proposed a computational method to estimate scintillation yield using Monte Carlo simulations considering the principle of the FRET (fluorescence resonance energy transfer) process, which is a phenomenon of energy transfer between fluorescent molecules. In their study, the track structure simulations could reproduce measured yields of scintillation. However, Ogawa et al.'s model was not suitable for estimating the scintillation yields when the particle energy was low when using condensed history simulations. Therefore, we propose a new method for estimating scintillation yields more accurately using Geant4 to improve the model calculations based on condensed history simulations. We simulated the local energy deposition pattern in a NE102A plastic scintillator to calculate the number of excitors in the microscopic volume for various nuclides (helium to argon ions). The suppressed scintillation yields were estimated using the model calculations of sequential FRET processes while considering the inactivation of the excitors selected as donors of the FRET process. The model calculations successfully reproduced the experimental scintillation yields within 10% error for the lighter ions up to neon. However, when the analysis was repeated for silicon and argon, the maximum error in the scintillation yields increased up to 27%. The proposed computational model for the evaluation of the suppressed scintillation yields emitted from NE102A scintillator irradiated with heavy ions using sequential FRET calculations with condensed history method returned simulated scintillation yields.}, } @article {pmid34457325, year = {2021}, author = {Sakamoto, M and Benton, MJ and Venditti, C}, title = {Strong support for a heterogeneous speciation decline model in Dinosauria: a response to claims made by Bonsor et al. (2020).}, journal = {Royal Society open science}, volume = {8}, number = {8}, pages = {202143}, pmid = {34457325}, issn = {2054-5703}, abstract = {Through phylogenetic modelling, we previously presented strong support for diversification decline in the three major subclades of dinosaurs (Sakamoto et al. 2016 Proc. Natl Acad. Sci. USA 113, 5036-5040. (doi:10.1073/pnas.1521478113)). Recently, our support for this model has been criticized (Bonsor et al. 2020 R. Soc. Open Sci. 7, 201195. (doi:10.1098/rsos.201195)). Here, we highlight that these criticisms seem to largely stem from a misunderstanding of our study: contrary to Bonsor et al.'s claims, our model accounts for heterogeneity in diversification dynamics, was selected based on deviance information criterion (DIC) scores (not parameter significance), and intercepts were estimated to account for uncertainties in the root age of the phylogenetic tree. We also demonstrate that their new analyses are not comparable to our models: they fit simple, Dinosauria-wide models as a direct comparison to our group-wise models, and their additional trees are subclades that are limited in taxonomic coverage and temporal span, i.e. severely affected by incomplete sampling. We further present results of new analyses on larger, better-sampled trees (N = 961) of dinosaurs, showing support for the time-quadratic model. Disagreements in how we interpret modelled diversification dynamics are to be expected, but criticisms should be based on sound logic and understanding of the model under discussion.}, } @article {pmid34453335, year = {2021}, author = {Sun, Y and Zhu, Q and Huang, M and Shen, D and Zhou, Y and Feng, Q}, title = {Liver DCE-MRI registration based on sparse recovery of contrast agent curves.}, journal = {Medical physics}, volume = {48}, number = {11}, pages = {6916-6929}, doi = {10.1002/mp.15193}, pmid = {34453335}, issn = {2473-4209}, support = {2015B0101311011//Science and Technology Project of Guangdong Province/ ; 81801780//National Natural Science Foundation of China/ ; 202102020297//Guangzhou Science and Technology Project/ ; A2020311//Medical Scientific Research Foundation of Guangdong Province of China/ ; }, mesh = {Algorithms ; *Contrast Media ; Humans ; *Liver Neoplasms/diagnostic imaging ; Magnetic Resonance Imaging ; }, abstract = {PURPOSE: Dynamic contrast-enhanced MRI (DCE-MRI) registration is a challenging task because of the effect of remarkable intensity changes caused by contrast agent injections. Unrealistic deformation usually occurs by using traditional intensity-based algorithms. To alleviate the effect of contrast agent on registration, we proposed a DCE-MRI registration strategy and investigated the registration performance on the clinical DCE-MRI time series of liver.

METHOD: We reconstructed the time-intensity curves of the contrast agent through sparse representation with a predefined dictionary whose columns were the time-intensity curves with high correlations with respect to a preselected contrast agent curve. After reshaping 1D-reconstructed contrast agent time-intensity curves into a 4D contrast agent time series, we aligned the original time series to the reconstructed contrast agent time series through traditional free-form deformation (FFD) registration scheme combined with a residual complexity (RC) similarity and an iterative registration strategy. This study included the DCE-MRI time series of 20 patients with liver cancer.

RESULTS: Qualitatively, the time-cut images and subtraction images of different registration methods did not obviously differ. Quantitatively, the mean (standard deviation) of temporal intensity smoothness of all the patients achieved 54.910 (18.819), 54.609 (18.859), and 53.391 (19.031) in FFD RC, RDDR, Zhou et al.'s method and the proposed method, respectively. The mean (standard deviation) of changes in the lesion volume were 0.985 (0.041), 0.983 (0.041), 0.981 (0.046), and 0.989 (0.036) in FFD RC, RDDR, Zhou et al.'s method and the proposed method.

CONCLUSION: Our proposed method would be an effective registration strategy for DCE-MRI time series, and its performance was comparable with that of three advanced registration methods.}, } @article {pmid34447002, year = {2021}, author = {Datta, AK and Pandit, A and Biswas, S and Biswas, A and Roy, BK and Gangopaddhyay, G}, title = {Spectrum of Anti-NMDA Receptor Antibody Encephalitis: Clinical Profile, Management and Outcomes.}, journal = {Annals of Indian Academy of Neurology}, volume = {24}, number = {3}, pages = {383-389}, pmid = {34447002}, issn = {0972-2327}, abstract = {BACKGROUND: Anti-N-methyl D-aspartate receptor (anti NMDAR) antibody encephalitis is an immune-mediated entity characterised by a constellation of neuro-psychiatric symptoms.

OBJECTIVE: To describe clinical profile and treatment outcomes of patients with anti NMDAR antibody encephalitis.

SETTINGS AND DESIGN: Subjects were selected by screening for all patients satisfying Graus et al.'s criteria for probable anti NMDAR antibody encephalitis, admitted in neurology department of a tertiary care centre in Eastern India.

MATERIALS AND METHODS: A prospective, longitudinal study was conducted by identifying 25 patients with anti NMDAR antibodies in CSF and or serum, between September 2018 to February 2020.

STATISTICAL ANALYSIS: Chi square test was used to compare variables.

RESULTS: Out of 98 patients screened, 25 subjects (14 females: 11 male) were positive for anti NMDAR autoantibodies, with a mean age of 17 years. 13 subjects belonged to paediatric age group. Most common presenting feature was memory/learning deficit (88%) followed by behavioural abnormalities (84%) and seizures (68%). 11 patients (44%) patients needed escalation to second line therapy, rituximab. Seven (28%) and twelve (48%) patients underwent complete (mRS 0-1) and partial recovery (mRS 2-3) respectively, while 4 (16%) became disabled (mRS 4-5). Mortality was 8%. Paediatric population had a better outcome in terms of disability (p = 0.043).

CONCLUSION: Anti NMDAR-Ab encephalitis is the most common cause of antibody positive autoimmune encephalitis worldwide. There are important clinical markers and investigational profiles which carry prognostic significance.}, } @article {pmid34441120, year = {2021}, author = {Jia, H and Tang, C and Zhang, Y}, title = {Lattice-Based Logarithmic-Size Non-Interactive Deniable Ring Signatures.}, journal = {Entropy (Basel, Switzerland)}, volume = {23}, number = {8}, pages = {}, pmid = {34441120}, issn = {1099-4300}, support = {61802075, 61802241, 61902303//National Natural Science Foundation of China/ ; 2017YFB0802000//National Key R&D Program of China/ ; }, abstract = {Deniable ring signature can be regarded as group signature without group manager, in which a singer is capable of singing a message anonymously, but, if necessary, each ring member is allowed to confirm or disavowal its involvement in the signature via an interactive mechanism between the ring member and the verifier. This attractive feature makes the deniable ring signature find many applications in the real world. In this work, we propose an efficient scheme with signature size logarithmic to the cardinality of the ring. From a high level, we adapt Libert et al.'s zero-knowledge argument system (Eurocrypt 2016) to allow the prover to convince the verifier that its witness satisfies an additional condition. Then, using the Fait-Shamir transformation, we get a non-interactive deniable ring signature scheme that satisfies the anonymity, traceability, and non-frameability under the small integer solution assumption in the random oracle model.}, } @article {pmid34432889, year = {2021}, author = {Kosie, JE and Baldwin, DA}, title = {Dwell times showcase how goal structure informs preschoolers' analysis of unfolding motion patterns.}, journal = {Child development}, volume = {92}, number = {6}, pages = {2235-2243}, doi = {10.1111/cdev.13661}, pmid = {34432889}, issn = {1467-8624}, mesh = {Child ; Female ; *Goals ; Humans ; *Motivation ; }, abstract = {Using Hard et al.'s (2011) dwell-time paradigm, 85 preschoolers (aged 2.5-4.5; 43 female; primarily from white families) advanced at their own pace through one of three slideshows. All slideshows depicted an actor reaching toward, grasping, and retrieving a ball. However, motion patterns differed for one slideshow (straight-reach) relative to the other two (arcing-reaches), and one of the arcing-reach slideshows depicted a violation of typical goal-related motion. Preschoolers' knowledge of goal structure systematically modulated attention to event boundaries across slideshows despite surface differences, even when controlling for pixel change (an index of changes in motion). These findings showcase the value of the dwell time paradigm, and illuminate how children deploy attention as goal-related expectations shape their analysis of continuously unfolding activity.}, } @article {pmid34429484, year = {2021}, author = {Sutradhar, K and Om, H}, title = {Enhanced (t, n) threshold d-level quantum secret sharing.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {17083}, pmid = {34429484}, issn = {2045-2322}, abstract = {The quantum secret sharing is an essential and fundamental technique for sharing a secret with the all participants in quantum cryptography. It can be used to design many complex protocols such as secure multiparty summation, multiplication, sorting, voting, etc. Recently, Song et al. have discussed a quantum protocol for secret sharing, which has (t, n) threshold approach and modulo d, where t and n denote the threshold number of participants and total number of participants, respectively. Kao et al. point out that the secret in the Song et al.'s protocol cannot be reconstructed without other participants' information. In this paper, we discuss a protocol that overcomes this problem.}, } @article {pmid34428724, year = {2021}, author = {Slemon, A and Jenkins, EK and Bailey, E}, title = {Enhancing conceptual clarity of self-care for nursing students: A scoping review.}, journal = {Nurse education in practice}, volume = {55}, number = {}, pages = {103178}, doi = {10.1016/j.nepr.2021.103178}, pmid = {34428724}, issn = {1873-5223}, mesh = {Delivery of Health Care ; *Education, Nursing ; Humans ; Self Care ; *Students, Nursing ; }, abstract = {OBJECTIVE: This paper aims to explore how self-care is currently defined and conceptualized in nursing education literature and identify gaps in current conceptualizations of self-care for nursing students.

BACKGROUND: Given the considerable stressors experienced by nursing students, self-care is an important concept for enhancing well-being. However, self-care has been poorly defined in the literature to date, contributing to challenges in integrating self-care into nursing education in support of student mental health and well-being.

DESIGN: A scoping review was undertaken in accordance with Arksey and O'Malley's (2005) framework and Levac et al.'s (2010) subsequent guidance.

METHODS: The search was conducted up to 1 September 2020 across three databases: Medline (OVID), PsycINFO and CINAHL. Search terms 'self-care', 'nursing students' and 'nursing education' were used. Criteria for inclusion of articles included peer-reviewed articles published in English that addressed self-care in the context of nursing education and/or nursing students and provided a definition of self-care. Two reviewers independently screened 1181 records by title and abstract, with a third reviewer resolving discrepancies. Subsequently, full-text review was completed for 119 articles.

RESULTS: Twenty-seven studies were included in the review, including 21 empirical articles and 6 non-empirical articles. Sixteen (59%) articles described an educational intervention, including self-care courses, assignments, or integration of self-care modalities as a classroom activity. Qualitative thematic analysis of article aims, and self-care definitions illustrated three central themes in the conceptualization of self-care: self-care as an aspect of holistic nursing; self-care as practices that ensure a healthy lifestyle; and self-care as activities undertaken in response to stress.

CONCLUSIONS: There is considerable variability in how self-care for nursing students is conceptualized, contributing to inconsistencies in the integration of this concept into nursing education. Nurse educators are encouraged to support students in identifying their own self-care strategies and engage in reflection and action toward shifting systemic contributors to stress and burnout among nursing students.}, } @article {pmid34424757, year = {2021}, author = {Zuckerman, AL and Lo, SM}, title = {Transfer Student Experiences and Identity Navigation in STEM: Overlapping Figured Worlds of Success.}, journal = {CBE life sciences education}, volume = {20}, number = {3}, pages = {ar48}, pmid = {34424757}, issn = {1931-7913}, support = {R25 NS119707/NS/NINDS NIH HHS/United States ; }, mesh = {*Engineering ; Humans ; Mathematics ; *Students ; Technology ; Universities ; }, abstract = {Community colleges are a pathway in higher education for many students, including students who are pursuing baccalaureate degrees in science, technology, engineering, and mathematics (STEM). Because of the increased demand for professionals in the STEM workforce, a successful transition from community colleges to the university setting is essential for increasing the number of transfer students who complete STEM degree programs. Fostering a stabilized academic transition for transfer students requires an understanding of how different academic and sociocultural backgrounds can influence students' identity trajectories during their undergraduate education. In this study, Holland et al.'s framework of figured worlds was used to examine how transfer students pursuing STEM degrees negotiated their identities in their transition to the university. Because identity is a complex construct that can influence student experiences in STEM, this study examined areas of compatible and incompatible expectations of what constitutes success across the university, community college, and high school learning environments, and among students, families, and faculty. Inconsistent expectations across these figured worlds provide insight into the challenges associated with the community college to university transition that can affect transfer students' experiences and identity production at the university.}, } @article {pmid34423011, year = {2021}, author = {Canavese, F and Mansour, M and Souchon, L and Samba, A and Dimeglio, A}, title = {The 'Hybrid method' for the treatment of congenital clubfoot.}, journal = {Annals of translational medicine}, volume = {9}, number = {13}, pages = {1099}, pmid = {34423011}, issn = {2305-5839}, abstract = {BACKGROUND: The hybrid method combines the advantages of the Ponseti technique and of the French Physical Therapy method. The main goal of this study is to present our results on 139 consecutive newborns with clubfoot (n=212 feet) treated at our Institution with the hybrid method.

METHODS: From May 2010 until August 2020, 139 consecutive newborns with congenital clubfoot (66 unilateral; 73 bilateral) were treated by the hybrid method protocol and were retrospectively reviewed. All patients were admitted via the maternity ward with their family and personal history records, i.e., parental age, parity, gender, birth weight, involved side and presence/absence of associated medical conditions. At birth, all clubfeet were graded in ascending order of severity according to Dimeglio et al.'s classification system. AP and lateral radiographs of each foot are taken every 5 to 6 months from age 6 months to 2 years, then once a year until age 4 years, to assess divergence between talus and calcaneus on both projections.

RESULTS: The cohort counted a total of 100 boys (71.9%) and 39 girls (28.1%). Clubfoot was unilateral in 66 patients (47.5%) and bilateral in 73 (52.5%). All but 10 patients had idiopathic clubfoot deformity (92.8%). Mean number of casts per patient was 8 (range: 4-11). One hundred and thirty patients out of 139 underwent percutaneous Achilles tenotomy under general anesthesia (93.5%). Overall, tibialis anterior transfer was performed in 6/212 feet (2.8%), posterior release in 9/212 (4.2%) and medial release in 1/212 foot (0.05%).

CONCLUSIONS: Our experience with the hybrid method has allowed us to constantly reduce the number of patients requiring surgery over the years, as well as the extent of surgical release. These results are encouraging, but larger cohorts of patients from different institutions and with longer follow up are needed to confirm our findings.}, } @article {pmid34417845, year = {2021}, author = {Lu, C and Yang, B and Cui, X and Wang, S and Qu, C and Zhang, W and Zhou, B}, title = {Characteristics and Environmental Response of White Secondary Mineral Precipitate in the Acid Mine Drainage From Jinduicheng Mine, Shaanxi, China.}, journal = {Bulletin of environmental contamination and toxicology}, volume = {107}, number = {6}, pages = {1012-1021}, pmid = {34417845}, issn = {1432-0800}, support = {No.18JS087//Scientific Research Program Funded by Shaanxi Provincial Education Department/ ; }, mesh = {China ; *Environmental Monitoring ; Minerals/analysis ; Mining ; Spectroscopy, Fourier Transform Infrared ; *Water Pollutants, Chemical/analysis ; }, abstract = {The study focuses on the white secondary mineral precipitate and its environmental response formed in acid mine drainage (AMD) at Jinduicheng Mine (Shaanxi, China). The mineral composition of white precipitate was characterized by Scanning electron microscopy-energy dispersive spectrometer (SEM-EDS), X-ray photoelectron spectroscopy (XRD), Fourier transform infrared spectroscopy (FT-IR), X-ray photoelectron spectroscopy (XPS), Inductively coupled plasma-atomic emission spectrometer (ICP-AES), chemical quantitative calculation and PHREEQC software. The white precipitate was a kind of amorphous crystal with the characteristics of a fine powder, and its main elements were O, Al, S, F, OH[-] and SO4[2-] groups. Moreover, by comparing the mole number of chemical elements, the main mineral composition of the white precipitate was closest to basaluminite. The geochemical simulation result of the PHREEQC software verified that the white precipitate was basaluminite. According to the analysis of water quality characteristics of water samples, basaluminite can reduce the ions content in the AMD and enrich Cu, Ni, Mo, Cr and F ions, showing an excellent self-purification capacity of the water body. These results are helpful to improve the understanding of secondary mineral and its environmental response, and are of great significance for the environmental protection and sustainable development of mining area.}, } @article {pmid34408067, year = {2021}, author = {}, title = {Erratum: Liu et al., "S-Nitrosylation of Divalent Metal Transporter 1 Enhances Iron Uptake to Mediate Loss of Dopaminergic Neurons and Motoric Deficit".}, journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, volume = {41}, number = {37}, pages = {7921}, doi = {10.1523/JNEUROSCI.1197-21.2021}, pmid = {34408067}, issn = {1529-2401}, } @article {pmid34405231, year = {2021}, author = {O'Connor, P and Madden, C and O'Dowd, E and Byrne, D and Lydon, S}, title = {A meta-review of methods of measuring and monitoring safety in primary care.}, journal = {International journal for quality in health care : journal of the International Society for Quality in Health Care}, volume = {33}, number = {3}, pages = {}, pmid = {34405231}, issn = {1464-3677}, mesh = {Checklist ; Humans ; *Patient Safety ; *Primary Health Care ; Reproducibility of Results ; Systematic Reviews as Topic ; }, abstract = {BACKGROUND: A major barrier to safety improvement in primary care is a lack of safety data. The aims of this systematic meta-review (registration: CRD42021224367) were to identify systematic reviews of studies that examine methods of measuring and monitoring safety in primary care; classify the methods of measuring and monitoring safety in the included systematic reviews using the five safety domains of Vincent et al.'s framework and use this information to make recommendations for improving the measurement and monitoring of safety in primary care.

METHODS: Four databases (Medline, Academic Search Complete, Web of Science and CINAHL) and the grey literature were screened in November 2020, with searches updated in January 2021. Systematic reviews were included if they addressed the measurement of patient safety in primary care and were published in English. Studies were assessed using the Critical Appraisal Skills Programme for systematic reviews.

RESULTS: A total of 6904 papers were screened, with 13 systematic reviews included. A commonly reported method of measuring 'past harm' was through patient record review. The most frequent methods for assessing the 'reliability of safety critical processes' were checklists, observations and surveys of staff. Methods used to assess 'sensitivity to operations' included observation, staff surveys, interviews, focus groups, active monitoring and simulated patients. Safety climate surveys were a commonly used as an approach to assess 'anticipation and preparedness'. A number of the reviews concluded that safety data could, and should, be used for 'integration and learning'. The main limitation of the meta-review was that it was of systematic reviews only.

CONCLUSIONS: Many of the methods for measuring and monitoring safety are readily available, quick to administer, do not require external involvement and are inexpensive. However, there is still a need to improve the psychometric properties of many measures. Researchers must support the development of psychometrically sound safety measures that do not over burden primary care practitioners. Policymakers must consider how primary care practitioners can be supported to implement these measures.}, } @article {pmid34396104, year = {2021}, author = {Sol, J and Jové, M and Povedano, M and Sproviero, W and Domínguez, R and Piñol-Ripoll, G and Romero-Guevara, R and Hye, A and Al-Chalabi, A and Torres, P and Andres-Benito, P and Area-Gómez, E and Pamplona, R and Ferrer, I and Ayala, V and Portero-Otín, M}, title = {Lipidomic traits of plasma and cerebrospinal fluid in amyotrophic lateral sclerosis correlate with disease progression.}, journal = {Brain communications}, volume = {3}, number = {3}, pages = {fcab143}, pmid = {34396104}, issn = {2632-1297}, support = {AL-CHALABI/APR15/844-791/MNDA_/Motor Neurone Disease Association/United Kingdom ; }, abstract = {Since amyotrophic lateral sclerosis cases exhibit significant heterogeneity, we aim to investigate the association of lipid composition of plasma and CSF with amyotrophic lateral sclerosis diagnosis, its progression and clinical characteristics. Lipidome analyses would help to stratify patients on a molecular basis. For this reason, we have analysed the lipid composition of paired plasma and CSF samples from amyotrophic lateral sclerosis cases and age-matched non-amyotrophic lateral sclerosis individuals (controls) by comprehensive liquid chromatography coupled to mass spectrometry. The concentrations of neurofilament light chain-an index of neuronal damage-were also quantified in CSF samples and plasma. Amyotrophic lateral sclerosis versus control comparison, in a moderate stringency mode, showed that plasma from cases contains more differential lipids (n = 122 for raw P < 0.05; n = 27 for P < 0.01) than CSF (n = 17 for raw P < 0.05; n = 4 for P < 0.01), with almost no overlapping differential species, mainly characterized by an increased content of triacylglyceride species in plasma and decreased in CSF. Of note, false discovery rate correction indicated that one of the CSF lipids (monoacylglycerol 18:0) had high statistic robustness (false discovery rate-P < 0.01). Plasma lipidomes also varied significantly with the main involvement at onset (bulbar, spinal or respiratory). Notably, faster progression cases showed particular lipidome fingerprints, featured by decreased triacylclycerides and specific phospholipids in plasma, with 11 lipids with false discovery rate-P < 0.1 (n = 56 lipids in plasma for raw P < 0.01). Lipid species associated with progression rate clustered in a relatively low number of metabolic pathways, mainly triacylglyceride metabolism and glycerophospholipid and sphingolipid biosynthesis. A specific triacylglyceride (68:12), correlated with neurofilament content (r = 0.8, P < 0.008). Thus, the present findings suggest that systemic hypermetabolism-potentially sustained by increased triacylglyceride content-and CNS alterations of specific lipid pathways could be associated as modifiers of disease progression. Furthermore, these results confirm biochemical lipid heterogeneity in amyotrophic lateral sclerosis with different presentations and progression, suggesting the use of specific lipid species as potential disease classifiers.}, } @article {pmid34393879, year = {2021}, author = {Sousa, P and Allard, A and Piazza, J and Goodwin, GP}, title = {Folk Moral Objectivism: The Case of Harmful Actions.}, journal = {Frontiers in psychology}, volume = {12}, number = {}, pages = {638515}, pmid = {34393879}, issn = {1664-1078}, abstract = {It is controversial whether ordinary people regard beliefs about the wrongness of harmful actions as objectively correct. Our deflationary hypothesis, consistent with much of the evidence, is that people are objectivists about harmful actions that are perceived to involve injustice: when two parties disagree about whether such an action is wrong, people think that only one party is correct (the party believing that the action is wrong). However, Sarkissian and colleagues claimed that this evidence is misleading, showing that when the two disagreeing parties are from radically different cultures or species, people tend to think that both parties are correct (a non-objectivist position). We argue that Sarkissian et al.'s studies have some methodological limitations. In particular, participants may have assumed that the exotic or alien party misunderstood the harmful action, and this assumption, rather than a genuinely non-objectivist stance, may have contributed to the increase in non-objectivist responses. Study 1 replicated Sarkissian et al.'s results with additional follow-up measures probing participants' assumptions about how the exotic or alien party understood the harmful action, which supported our suspicion that their results are inconclusive and therefore do not constitute reliable evidence against the deflationary hypothesis. Studies 2 and 3 modified Sarkissian et al.'s design to provide a clear-cut and reliable test of the deflationary hypothesis. In Study 2, we addressed potential issues with their design, including those concerning participants' assumptions about how the exotic or alien party understood the harmful action. In Study 3, we manipulated the alien party's capacity to understand the harmful action. With these changes to the design, high rates of objectivism emerged, consistent with the deflationary hypothesis. Studies 4a and 4b targeted the deflationary hypothesis more precisely by manipulating perceptions of injustice to see the effect on objectivist responding and by probing the more specific notion of objectivism entailed by our hypothesis. The results fully supported the deflationary hypothesis.}, } @article {pmid34390790, year = {2022}, author = {Xiao, M and Chu, H and Cole, SR and Chen, Y and MacLehose, RF and Richardson, DB and Greenland, S}, title = {Controversy and Debate : Questionable utility of the relative risk in clinical research: Paper 4 :Odds Ratios are far from "portable" - A call to use realistic models for effect variation in meta-analysis.}, journal = {Journal of clinical epidemiology}, volume = {142}, number = {}, pages = {294-304}, pmid = {34390790}, issn = {1878-5921}, support = {R01 LM012607/LM/NLM NIH HHS/United States ; R01 LM012982/LM/NLM NIH HHS/United States ; R01 LM013049/LM/NLM NIH HHS/United States ; UL1 TR002494/TR/NCATS NIH HHS/United States ; }, mesh = {Bias ; Causality ; Humans ; *Odds Ratio ; Risk ; Systematic Reviews as Topic ; }, abstract = {OBJECTIVE: Recently Doi et al. argued that risk ratios should be replaced with odds ratios in clinical research. We disagreed, and empirically documented the lack of portability of odds ratios, while Doi et al. defended their position. In this response we highlight important errors in their position.

STUDY DESIGN AND SETTING: We counter Doi et al.'s arguments by further examining the correlations of odds ratios, and risk ratios, with baseline risks in 20,198 meta-analyses from the Cochrane Database of Systematic Reviews.

RESULTS: Doi et al.'s claim that odds ratios are portable is invalid because 1) their reasoning is circular: they assume a model under which the odds ratio is constant and show that under such a model the odds ratio is portable; 2) the method they advocate to convert odds ratios to risk ratios is biased; 3) their empirical example is readily-refuted by counter-examples of meta-analyses in which the risk ratio is portable but the odds ratio isn't; and 4) they fail to consider the causal determinants of meta-analytic inclusion criteria: Doi et al. mistakenly claim that variation in odds ratios with different baseline risks in meta-analyses is due to collider bias. Empirical comparison between the correlations of odds ratios, and risk ratios, with baseline risks show that the portability of odds ratios and risk ratios varies across settings.

CONCLUSION: The suggestion to replace risk ratios with odds ratios is based on circular reasoning and a confusion of mathematical and empirical results. It is especially misleading for meta-analyses and clinical guidance. Neither the odds ratio nor the risk ratio is universally portable. To address this lack of portability, we reinforce our suggestion to report variation in effect measures conditioning on modifying factors such as baseline risk; understanding such variation is essential to patient-centered practice.}, } @article {pmid34387519, year = {2021}, author = {Vaughan-Johnston, TI and Jacobson, JA and Prosserman, A and Sanders, E}, title = {Mind-Body Practices and Self-Enhancement: Direct Replications of Gebauer et al.'s (2018) Experiments 1 and 2.}, journal = {Psychological science}, volume = {32}, number = {9}, pages = {1510-1521}, doi = {10.1177/0956797621997366}, pmid = {34387519}, issn = {1467-9280}, mesh = {Canada ; Humans ; *Meditation ; Self Concept ; Students ; *Yoga ; }, abstract = {Mind-body practices such as yoga and meditation are often believed to instill a "quiet ego," entailing less self-enhancement. In two experiments, however, Gebauer et al. (2018) demonstrated that mind-body practices may actually increase self-enhancement, particularly because such practices become self-central bases for self-esteem. We conducted preregistered replications of both of Gebauer et al.'s experiments. Experiment 1 was a field study of Canadian yoga students (N = 97), and Experiment 2 was a multiwave meditation intervention among Canadian university students (N = 300). Our results supported Gebauer et al.'s original conclusions that mind-body practices increase self-enhancement. Although the self-centrality effects were not clearly replicated in either experiment, we found evidence that measurement and sampling differences may explain this discrepancy. Moreover, an integrative data analysis of the original and the replication data strongly supported all of Gebauer et al.'s conclusions. In short, we provide new evidence against the ego-quieting perspective and in support of the self-centrality interpretation of mind-body practices.}, } @article {pmid34384876, year = {2022}, author = {Xiao, M and Chen, Y and Cole, SR and MacLehose, RF and Richardson, DB and Chu, H}, title = {Controversy and Debate: Questionable utility of the relative risk in clinical research: Paper 2: Is the Odds Ratio "portable" in meta-analysis? Time to consider bivariate generalized linear mixed model.}, journal = {Journal of clinical epidemiology}, volume = {142}, number = {}, pages = {280-287}, pmid = {34384876}, issn = {1878-5921}, support = {R01 LM012982/LM/NLM NIH HHS/United States ; UL1 TR002494/TR/NCATS NIH HHS/United States ; R01 LM013049/LM/NLM NIH HHS/United States ; R01 LM012607/LM/NLM NIH HHS/United States ; }, mesh = {Humans ; Linear Models ; *Odds Ratio ; Risk ; Systematic Reviews as Topic ; }, abstract = {OBJECTIVES: A recent paper by Doi et al. advocated completely replacing the relative risk (RR) with the odds ratio (OR) as the effect measure in clinical trials and meta-analyses with binary outcomes. Besides some practical advantages of RR over OR, Doi et al.'s key assumption that the OR is "portable" in the meta-analysis, that is, study-specific ORs are likely not correlated with baseline risks, was not well justified.

STUDY DESIGNS AND SETTINGS: We summarized Spearman's rank correlation coefficient between study-specific ORs and baseline risks in 40,243 meta-analyses from the Cochrane Database of Systematic Reviews.

RESULTS: Study-specific ORs tend to be higher in studies with lower baseline risks of disease for most meta-analyses in Cochrane Database of Systematic Reviews. Using an actual meta-analysis example, we demonstrate that there is a strong negative correlation between OR (RR or RD) with the baseline risk and the conditional effects notably vary with baseline risks.

CONCLUSIONS: Replacing RR or RD with OR is currently unadvisable in clinical trials and meta-analyses. It is possible that no effect measure is "portable" in a meta-analysis. In addition to the overall (or marginal) effect, we suggest presenting the conditional effect based on the baseline risk using a bivariate generalized linear mixed model.}, } @article {pmid34383363, year = {2021}, author = {Cuartero, MC and Bertrand, R and Rauzy, S and Véron-Delor, L and Atkinson-Clement, C and Grabli, D and Vidailhet, M and Pinto, S}, title = {Acoustic, perceptual and clinical correlates of speech and voice in isolated dystonia: Preliminary findings.}, journal = {International journal of language & communication disorders}, volume = {56}, number = {6}, pages = {1204-1217}, doi = {10.1111/1460-6984.12661}, pmid = {34383363}, issn = {1460-6984}, mesh = {Acoustics ; Dysarthria/diagnosis/etiology ; *Dystonia ; Humans ; Speech Acoustics ; Speech Intelligibility ; Speech Production Measurement ; }, abstract = {BACKGROUND: Hyperkinetic dysarthria is often present in isolated dystonia (ID) and is still understudied. Four main clusters of deviant speech dimensions in dystonia hyperkinetic dysarthria were initially provided: articulatory inaccuracy, phonatory stenosis, prosodic excess and prosodic insufficiency.

AIM: The aim of our exploratory study was to provide preliminary data on both perceptual and acoustic analyses in relation to three out of these four main clusters.

METHODS & PROCEDURES: Eleven patients with ID and 11 healthy controls (HC) participated in this study. Clinical/perceptual assessments and acoustic analyses of speech recordings were performed, the latter allowing for the analysis of parameters referring to aerophonatory control, voice quality, prosodic features and speech intelligibility estimated by nine listeners. Between-group statistical comparisons were performed (Wilcoxon tests, p < 0.05). Single-case differences between each patient and the control group were also carried out (effect size index and t < 0.05).

OUTCOMES & RESULTS: Between-group comparisons confirmed the presence of a 'phonatory stenosis'; in addition, deficit in aerophonatory control and hypophonia was also displayed. 'Prosodic insufficiency' was confirmed, but not at the individual level. 'Prosodic excess' manifested only in patients with marked and severe dysarthria. Correlations between altered maximum phonation time, loudness variation, speech and articulatory rates on the one hand, and several clinical speech assessments on the other hand, were also found.

From these findings, altogether, perceptual characteristics of hyperkinetic dysarthria, as suggested by Darley et al., were quantified by the acoustic parameters we measured. As regards to our data obtained in a small participant sample, we would suggest that Darley et al.'s clusters of excess and insufficiency prosody should be questioned in future studies involving larger numbers of dystonic patients. Our study provides novel and preliminary results that demonstrate the relevance of using quantitative measures to further characterise speech/voice deficits in patients with ID.}, } @article {pmid34376878, year = {2021}, author = {Heibi, I and Peroni, S}, title = {A qualitative and quantitative analysis of open citations to retracted articles: the Wakefield 1998 et al.'s case.}, journal = {Scientometrics}, volume = {126}, number = {10}, pages = {8433-8470}, pmid = {34376878}, issn = {0138-9130}, abstract = {In this article, we show the results of a quantitative and qualitative analysis of open citations on a popular and highly cited retracted paper: "Ileal-lymphoid-nodular hyperplasia, non-specific colitis and pervasive developmental disorder in children" by Wakefield et al., published in 1998. The main purpose of our study is to understand the behavior of the publications citing one retracted article and the characteristics of the citations the retracted article accumulated over time. Our analysis is based on a methodology which illustrates how we gathered the data, extracted the topics of the citing articles and visualized the results. The data and services used are all open and free to foster the reproducibility of the analysis. The outcomes concerned the analysis of the entities citing Wakefield et al.'s article and their related in-text citations. We observed a constant increasing number of citations in the last 20 years, accompanied with a constant increment in the percentage of those acknowledging its retraction. Citing articles have started either discussing or dealing with the retraction of Wakefield et al.'s article even before its full retraction happened in 2010. Articles in the social sciences domain citing the Wakefield et al.'s one were among those that have mostly discussed its retraction. In addition, when observing the in-text citations, we noticed that a large number of the citations received by Wakefield et al.'s article has focused on general discussions without recalling strictly medical details, especially after the full retraction. Medical studies did not hesitate in acknowledging the retraction of the Wakefield et al.'s article and often provided strong negative statements on it.}, } @article {pmid34370493, year = {2022}, author = {Kiang, L and Wilkinson, BC and Juang, LP}, title = {The markings of linked fate among Asian Americans and Latinxs.}, journal = {Cultural diversity & ethnic minority psychology}, volume = {28}, number = {4}, pages = {523-532}, doi = {10.1037/cdp0000482}, pmid = {34370493}, issn = {1099-9809}, mesh = {Humans ; *Asian ; Minority Groups ; *Emigrants and Immigrants ; Racial Groups ; Residence Characteristics ; }, abstract = {OBJECTIVE: Linked fate, or the degree to which individuals feel that their lives are tied to other group members' lives, can mobilize collective action and strengthen commonalities. Yet, linked fate remains underresearched, particularly among Asian Americans and Latinxs.

METHOD: Using the 2016 Collaborative Multiracial Postelection Survey, the present study draws on García Coll et al.'s (1996) integrative model to examine associations between three domains of linked fate (immigrant, minority, coethnic) and demographic and structural factors (age, gender, nativity, education, income, language, skin color, neighborhood diversity, social stratification).

RESULTS: Education, discrimination, and feeling excluded are positively related to immigrant, minority, and coethnic-linked fate; age is negatively related. Income and nativity were not significant predictors.

CONCLUSIONS: Implications for fostering linked fate and coalition building within and across Asians and Latinxs are discussed. (PsycInfo Database Record (c) 2022 APA, all rights reserved).}, } @article {pmid34369321, year = {2021}, author = {Serra-Negra, JM and Dias, RB and Manfredini, D}, title = {Sleep bruxism, chronotype, and cardiovascular issues - an interesting triad. Dr. Júnia Serra-Negra et al.'s reply.}, journal = {Cranio : the journal of craniomandibular practice}, volume = {39}, number = {5}, pages = {459-460}, doi = {10.1080/08869634.2021.1956788}, pmid = {34369321}, issn = {2151-0903}, mesh = {Humans ; Sleep ; *Sleep Bruxism/complications ; }, } @article {pmid34344248, year = {2022}, author = {Galarraga, DB and Pratt, J and Cochrane, BA}, title = {Is the attentional SNARC effect truly attentional? Using temporal order judgements to differentiate attention from response.}, journal = {Quarterly journal of experimental psychology (2006)}, volume = {75}, number = {5}, pages = {808-817}, pmid = {34344248}, issn = {1747-0226}, mesh = {*Functional Laterality/physiology ; Hand ; Humans ; Judgment/physiology ; Reaction Time/physiology ; *Space Perception/physiology ; }, abstract = {The spatial-numerical association of response codes (SNARC) effect reflects the phenomenon that low digits are responded to faster with the left hand and high digits with the right. Recently, a particular variant of the SNARC effect known as the attentional SNARC (which reflects that attention can be shifted in a similar manner) has had notable replicability issues. However, a potentially useful method for measuring it was revealed by Casarotti et al. using a temporal order judgement (TOJ) task. Accordingly, the present study evaluated whether Casarotti et al.'s results were reproducible by presenting a low (1) or high (9) digit prior to a TOJ task where participants had to indicate which of two peripherally presented targets appeared first (Experiment 1) or second (Experiment 2). In Experiment 1, it was revealed that the findings of Casarotti et al.'s were indeed observable upon replication. In Experiment 2, when attention and response dimensions were put in opposition, the SNARC effect corresponded to the side of response rather than attention. Taken together, the present study confirms the robustness of the attentional SNARC in TOJ tasks, but that it is not likely due to shifts in attention.}, } @article {pmid34330329, year = {2021}, author = {Rafiei Alavi, SN and Madani Neishaboori, A and Hossein, H and Sarveazad, A and Yousefifard, M}, title = {Efficacy of adipose tissue-derived stem cells in locomotion recovery after spinal cord injury: a systematic review and meta-analysis on animal studies.}, journal = {Systematic reviews}, volume = {10}, number = {1}, pages = {213}, pmid = {34330329}, issn = {2046-4053}, mesh = {Adipose Tissue ; Animals ; Disease Models, Animal ; Humans ; Locomotion ; Rats ; Recovery of Function ; *Spinal Cord Injuries/therapy ; Stem Cells ; }, abstract = {BACKGROUND: Considerable disparities exist on the use of adipose tissue-derived stem cells (ADSCs) for treatment of spinal cord injury (SCI). Hence, the current systematic review aimed to investigate the efficacy of ADSCs in locomotion recovery following SCI in animal models.

METHODS: A search was conducted in electronic databases of MEDLINE, Embase, Scopus, and Web of Science until the end of July 2019. Reference and citation tracking and searching Google and Google Scholar search engines were performed to achieve more studies. Animal studies conducted on rats having SCI which were treated with ADSCs were included in the study. Exclusion criteria were lacking a non-treated control group, not evaluating locomotion, non-rat studies, not reporting the number of transplanted cells, not reporting isolation and preparation methods of stem cells, review articles, combination therapy, use of genetically modified ADSCs, use of induced pluripotent ADSCs, and human trials. Risk of bias was assessed using Hasannejad et al.'s proposed method for quality control of SCI-animal studies. Data were analyzed in STATA 14.0 software, and based on a random effect model, pooled standardized mean difference with a 95% confidence interval was presented.

RESULTS: Of 588 non-duplicated papers, data from 18 articles were included. Overall risk of bias was high risk in 8 studies, some concern in 9 studies and low risk in 1 study. Current evidence demonstrated that ADSCs transplantation could improve locomotion following SCI (standardized mean difference = 1.71; 95%CI 1.29-2.13; p < 0.0001). A considerable heterogeneity was observed between the studies (I[2] = 72.0%; p < 0.0001). Subgroup analysis and meta-regression revealed that most of the factors like injury model, the severity of SCI, treatment phase, injury location, and number of transplanted cells did not have a significant effect on the efficacy of ADSCs in improving locomotion following SCI (pfor odds ratios > 0.05).

CONCLUSION: We conclude that any number of ADSCs by any prescription routes can improve locomotion recovery in an SCI animal model, at any phase of SCI, with any severity. Given the remarkable bias about blinding, clinical translation of the present results is tough, because in addition to the complexity of the nervous system and the involvement of far more complex motor circuits in the human, blinding compliance and motor outcome assessment tests in animal studies and clinical trials are significantly different.}, } @article {pmid34329267, year = {2021}, author = {Chen, YP and Liu, JY and Sun, MS and Zhou, XX and Zhang, CH and Li, J and Wang, Q}, title = {Experimental measurement-device-independent quantum key distribution with the double-scanning method.}, journal = {Optics letters}, volume = {46}, number = {15}, pages = {3729-3732}, doi = {10.1364/OL.431061}, pmid = {34329267}, issn = {1539-4794}, abstract = {The measurement-device-independent quantum key distribution (MDI-QKD) can be immune to all detector side-channel attacks. Moreover, it can be easily implemented combining with the matured decoy-state methods under current technology. It, thus, seems a very promising candidate in practical implementation of quantum communications. However, it suffers from a severe finite-data-size effect in most existing MDI-QKD protocols, resulting in relatively low key rates. Recently, Jiang et al. [Phys. Rev. A103, 012402 (2021).PLRAAN1050-294710.1103/PhysRevA.103.012402] proposed a double-scanning method to drastically increase the key rate of MDI-QKD. Based on Jiang et al.'s theoretical work, here we for the first time, to the best of our knowledge, implement the double-scanning method into MDI-QKD and carry out corresponding experimental demonstration. With a moderate number of pulses of 10[10], we can achieve 150 km secure transmission distance, which is impossible with all former methods. Therefore, our present work paves the way toward practical implementation of MDI-QKD.}, } @article {pmid34320527, year = {2021}, author = {Myerson, J and Tye-Murray, N and Spehar, B and Hale, S and Sommers, M}, title = {Predicting Audiovisual Word Recognition in Noisy Situations: Toward Precision Audiology.}, journal = {Ear and hearing}, volume = {42}, number = {6}, pages = {1656-1667}, pmid = {34320527}, issn = {1538-4667}, support = {R01 AG018029/AG/NIA NIH HHS/United States ; R01 DC016594/DC/NIDCD NIH HHS/United States ; R56 AG018029/AG/NIA NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; *Audiology ; Bayes Theorem ; Female ; Hearing ; Humans ; Male ; Middle Aged ; Noise ; *Speech Perception ; Visual Perception ; Young Adult ; }, abstract = {OBJECTIVE: Spoken communication is better when one can see as well as hear the talker. Although age-related deficits in speech perception were observed, Tye-Murray and colleagues found that even when age-related deficits in audiovisual (AV) speech perception were observed, AV performance could be accurately predicted from auditory-only (A-only) and visual-only (V-only) performance, and that knowing individuals' ages did not increase the accuracy of prediction. This finding contradicts conventional wisdom, according to which age-related differences in AV speech perception are due to deficits in the integration of auditory and visual information, and our primary goal was to determine whether Tye-Murray et al.'s finding with a closed-set test generalizes to situations more like those in everyday life. A second goal was to test a new predictive model that has important implications for audiological assessment.

DESIGN: Participants (N = 109; ages 22-93 years), previously studied by Tye-Murray et al., were administered our new, open-set Lex-List test to assess their auditory, visual, and audiovisual perception of individual words. All testing was conducted in six-talker babble (three males and three females) presented at approximately 62 dB SPL. The level of the audio for the Lex-List items, when presented, was approximately 59 dB SPL because pilot testing suggested that this signal-to-noise ratio would avoid ceiling performance under the AV condition.

RESULTS: Multiple linear regression analyses revealed that A-only and V-only performance accounted for 87.9% of the variance in AV speech perception, and that the contribution of age failed to reach significance. Our new parabolic model accounted for even more (92.8%) of the variance in AV performance, and again, the contribution of age was not significant. Bayesian analyses revealed that for both linear and parabolic models, the present data were almost 10 times as likely to occur with a reduced model (without age) than with a full model (with age as a predictor). Furthermore, comparison of the two reduced models revealed that the data were more than 100 times as likely to occur with the parabolic model than with the linear regression model.

CONCLUSIONS: The present results strongly support Tye-Murray et al.'s hypothesis that AV performance can be accurately predicted from unimodal performance and that knowing individuals' ages does not increase the accuracy of that prediction. Our results represent an important initial step in extending Tye-Murray et al.'s findings to situations more like those encountered in everyday communication. The accuracy with which speech perception was predicted in this study foreshadows a form of precision audiology in which determining individual strengths and weaknesses in unimodal and multimodal speech perception facilitates identification of targets for rehabilitative efforts aimed at recovering and maintaining speech perception abilities critical to the quality of an older adult's life.}, } @article {pmid34314710, year = {2021}, author = {Koski, MH and MacQueen, D and Ashman, TL}, title = {Reply to Robson et al.}, journal = {Current biology : CB}, volume = {31}, number = {14}, pages = {R887-R888}, doi = {10.1016/j.cub.2021.06.020}, pmid = {34314710}, issn = {1879-0445}, mesh = {*Ozone ; Pigmentation ; Temperature ; *Ultraviolet Rays/adverse effects ; }, abstract = {Robson et al.'s commentary[1] on our article, 'Floral pigmentation has responded rapidly to global change in ozone and temperature'[2], questions the study's conclusion that floral ultraviolet (UV) pigmentation has responded to global change, particularly to total column ozone (TCO). Robson et al.[1] claim that our study spanned a time frame in which ozone was not declining and suggest no biological relationship between UV-B exposure and UV floral pigmentation. To support their claims, they selectively remove and reanalyze data. We respond with a critique of their interpretations of our results, and analyses of temporal patterns of TCO data from Koski et al.[2]. Despite Robson et al.'s concerns, our study continues to support a link between temporal changes in ozone and temperature, and temporal changes in UV floral pigmentation.}, } @article {pmid34309741, year = {2022}, author = {Dutton, E and Kirkegaard, E}, title = {The Negative Religiousness-IQ Nexus is a Jensen Effect on Individual-Level Data: A Refutation of Dutton et al.'s 'The Myth of the Stupid Believer'.}, journal = {Journal of religion and health}, volume = {61}, number = {4}, pages = {3253-3275}, pmid = {34309741}, issn = {1573-6571}, mesh = {Humans ; *Religion ; }, abstract = {A recent study by Dutton et al. (J Relig Health 59:1567-1579. https://doi.org/10.1007/s10943-019-00926-3 , 2020) found that the religiousness-IQ nexus is not on g when comparing different groups with various degrees of religiosity and the non-religious. It suggested, accordingly, that the nexus related to the relationship between specialized analytic abilities on the IQ test and autism traits, with the latter predicting atheism. The study was limited by the fact that it was on group-level data, it used only one measure of religiosity that measure may have been confounded by the social element to church membership and it involved relatively few items via which a Jensen effect could be calculated. Here, we test whether the religiousness-IQ nexus is on g with individual-level data using archival data from the Vietnam Experience Study, in which 4462 US veterans were subjected to detailed psychological tests. We used multiple measures of religiosity-which we factor-analysed to a religion-factor-and a large number of items. We found, contrary to the findings of Dutton et al. (2020), that the IQ differences with regard to whether or not subjects believed in God are indeed a Jensen effect. We also uncovered a number of anomalies, which we explore.}, } @article {pmid34309513, year = {2021}, author = {Higashi, TL and Pobegalov, G and Tang, M and Molodtsov, MI and Uhlmann, F}, title = {A Brownian ratchet model for DNA loop extrusion by the cohesin complex.}, journal = {eLife}, volume = {10}, number = {}, pages = {}, pmid = {34309513}, issn = {2050-084X}, support = {FC001750/MRC_/Medical Research Council/United Kingdom ; FC001750/CRUK_/Cancer Research UK/United Kingdom ; 15671/CRUK_/Cancer Research UK/United Kingdom ; FC001198/CRUK_/Cancer Research UK/United Kingdom ; FC001198/MRC_/Medical Research Council/United Kingdom ; FC001198/WT_/Wellcome Trust/United Kingdom ; FC001750/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Adenosine Triphosphatases/chemistry ; Cell Cycle Proteins/*chemistry ; Chromatin/chemistry ; Chromosomal Proteins, Non-Histone/*chemistry ; Chromosomes/*chemistry ; Computational Biology ; DNA/*chemistry ; Models, Molecular ; Protein Conformation ; Saccharomyces cerevisiae/genetics ; Saccharomyces cerevisiae Proteins/genetics ; Cohesins ; }, abstract = {The cohesin complex topologically encircles DNA to promote sister chromatid cohesion. Alternatively, cohesin extrudes DNA loops, thought to reflect chromatin domain formation. Here, we propose a structure-based model explaining both activities. ATP and DNA binding promote cohesin conformational changes that guide DNA through a kleisin N-gate into a DNA gripping state. Two HEAT-repeat DNA binding modules, associated with cohesin's heads and hinge, are now juxtaposed. Gripping state disassembly, following ATP hydrolysis, triggers unidirectional hinge module movement, which completes topological DNA entry by directing DNA through the ATPase head gate. If head gate passage fails, hinge module motion creates a Brownian ratchet that, instead, drives loop extrusion. Molecular-mechanical simulations of gripping state formation and resolution cycles recapitulate experimentally observed DNA loop extrusion characteristics. Our model extends to asymmetric and symmetric loop extrusion, as well as z-loop formation. Loop extrusion by biased Brownian motion has important implications for chromosomal cohesin function.}, } @article {pmid34294903, year = {2021}, author = {Sumara, I}, title = {Feeding nuclear pores with condensed ME-AL-S.}, journal = {Nature reviews. Molecular cell biology}, volume = {22}, number = {10}, pages = {651}, pmid = {34294903}, issn = {1471-0080}, mesh = {*Nuclear Pore ; }, } @article {pmid34294383, year = {2021}, author = {Conlon, A and Ashur, C and Washer, L and Eagle, KA and Hofmann Bowman, MA}, title = {Response to "Potential for bias in assessing risk and protective factors for COVID-19: Commentary on Conlon et al.'s 'Impact of the influenza vaccination on COVID-19 infection rates and Severity'".}, journal = {American journal of infection control}, volume = {49}, number = {8}, pages = {1090-1091}, pmid = {34294383}, issn = {1527-3296}, mesh = {*COVID-19 ; Humans ; *Influenza, Human/prevention & control ; Protective Factors ; SARS-CoV-2 ; Vaccination ; }, } @article {pmid34294382, year = {2021}, author = {Valente, PK}, title = {Potential for bias in assessing risk and protective factors for COVID-19: Commentary on Conlon et al.'s "Impact of the influenza vaccination on COVID-19 infection rates and severity".}, journal = {American journal of infection control}, volume = {49}, number = {8}, pages = {1089-1090}, pmid = {34294382}, issn = {1527-3296}, mesh = {*COVID-19 ; Humans ; *Influenza, Human/prevention & control ; Protective Factors ; SARS-CoV-2 ; Vaccination ; }, } @article {pmid34293987, year = {2022}, author = {Han, T and Proctor, RW}, title = {Effects of a neutral warning signal on spatial two-choice reactions.}, journal = {Quarterly journal of experimental psychology (2006)}, volume = {75}, number = {4}, pages = {754-764}, doi = {10.1177/17470218211037604}, pmid = {34293987}, issn = {1747-0226}, mesh = {*Attention ; Humans ; Reaction Time/physiology ; }, abstract = {Posner et al. reported that, at short fixed foreperiods, a neutral warning tone reduced reaction times (RTs) in a visual two-choice task while increasing error rates for both spatially compatible and incompatible stimulus-response mappings. Consequently, they concluded that alertness induced by the warning does not affect the efficiency of information processing but the setting of a response criterion. We conducted two experiments to determine the conditions under which the trade-off occurs. In Experiment 1, participants performed the same two-choice task as in Posner et al.'s study without RT feedback. Results showed that the warning tone speeded responses with no evidence of speed/accuracy trade-off. In Experiment 2, RT feedback was provided after each response, and a speed/accuracy trade-off was found for the 50-ms foreperiod. However, better information-processing efficiency was evident for the 200-ms foreperiod. We conclude that the foreperiod effect of a 50-ms foreperiod is a result of response criterion adjustment and that providing trial-level RT feedback is critical for replicating this pattern. However, fixed foreperiods of 200 ms or longer benefit both speed and accuracy, implying a more controlled preparation component that improves response efficiency.}, } @article {pmid34291841, year = {2021}, author = {Berninger, JP and Tillitt, DE}, title = {Response to Gard et al.'s (2021) Comments on the Critical Review "Polychlorinated Biphenyl Tissue-Concentration Thresholds for Survival, Growth, and Reproduction in Fish".}, journal = {Environmental toxicology and chemistry}, volume = {40}, number = {8}, pages = {2098-2109}, doi = {10.1002/etc.5074}, pmid = {34291841}, issn = {1552-8618}, mesh = {Animals ; Fishes ; *Polychlorinated Biphenyls ; Reproduction ; }, } @article {pmid34280619, year = {2021}, author = {White, S and Tait, D and Scammell, J}, title = {Nursing students' evolving professional values: Capturing their journey through co-operative inquiry.}, journal = {Nurse education in practice}, volume = {54}, number = {}, pages = {103117}, doi = {10.1016/j.nepr.2021.103117}, pmid = {34280619}, issn = {1873-5223}, mesh = {Curriculum ; *Education, Nursing, Baccalaureate ; Empathy ; England ; Humans ; *Students, Nursing ; }, abstract = {AIM/OBJECTIVE AND BACKGROUND: Despite a worldwide emphasis in nursing codes of practice that state nurses must uphold professional values to be caring and compassionate, evidence continues to emerge of poor-quality care standards. Existing literature attests to a tendency to deteriorating caring values as students' progress through their nursing programme. In response, one university in England exposed pre-registration nursing students to a values-based curriculum which embedded Todres et al.'s (2009) Humanising Values Framework.

DESIGN AND METHODS: This paper describes the later stages of a co-operative inquiry, where students as participants explore their evolving values around person-centred approaches to care as they engaged with clinical practice. Data were collected between 2013 and 2016.

RESULTS AND CONCLUSION: Findings reveal how students developed their confidence and resilience in the face of situations that challenged their value base by internalising a humanised approach to care. They demonstrated this in practice by using problem-based coping strategies, peer and mentor support. Engagement with a curriculum based on humanistic philosophy encouraged students as participants to feel confident in the practice of person-centred care.}, } @article {pmid34273110, year = {2022}, author = {Shevlin, M and Hyland, P and Nolan, E and Owczarek, M and Ben-Ezra, M and Karatzias, T}, title = {ICD-11 'mixed depressive and anxiety disorder' is clinical rather than sub-clinical and more common than anxiety and depression in the general population.}, journal = {The British journal of clinical psychology}, volume = {61}, number = {1}, pages = {18-36}, pmid = {34273110}, issn = {2044-8260}, mesh = {Anxiety/epidemiology ; Anxiety Disorders/diagnosis/epidemiology ; *Depression/diagnosis/epidemiology ; Humans ; *International Classification of Diseases ; Mood Disorders ; }, abstract = {BACKGROUND: The new International Classification of Diseases was published in 2018 (ICD-11; World Health Organization, 2018) and now includes 'Mixed depressive and anxiety disorder' (6A73: MDAD) designated as a mood disorder. This disorder is defined by symptoms of both anxiety and depression occurring more days than not, for a period of two weeks, and neither set of symptoms considered separately reaches a diagnostic threshold for either disorder. However, to date no study has examined the validity of these guidelines in a general population sample.

METHODS: Using Goldberg et al.'s (2017) guidelines regarding measurement of depression and anxiety, this study used factor mixture modelling (FMM) to examine the validity of the ICD-11 criteria of MDAD. Symptom endorsement rates are provided as well as demographic predictors and somatization outcomes.

RESULTS: Fit indices suggested the two-factor four-class solution was the best balance between model complexity and model fit. The results did not support a class that is subsyndromal to both anxiety and depression. On the contrary, we suggest that there exists a 'Comorbid' class that represents endorsement of both anxiety and depression symptoms at a higher level when compared to both 'anxiety' and 'depression' groups. Demographic predictors, as well as somatization and functional impairment outcomes, provided support for this FMM solution.

CONCLUSIONS: The 'Comorbid' group was the largest symptomatic group and had the highest levels of both anxiety and depression symptoms. Importantly, this group was larger than either the 'anxiety' or 'depression' group and was associated with high levels of functional impairment and somatization.}, } @article {pmid34273084, year = {2021}, author = {O'Mahony, JF}, title = {Comment on Keeney et al.'s "Delphi Analysis of Relevant Comparators in a Cost-Effectiveness Model of Prostate Cancer Screening".}, journal = {PharmacoEconomics}, volume = {39}, number = {8}, pages = {965-967}, pmid = {34273084}, issn = {1179-2027}, mesh = {Cost-Benefit Analysis ; *Early Detection of Cancer ; Humans ; Male ; Prostate-Specific Antigen ; *Prostatic Neoplasms/diagnosis ; Quality-Adjusted Life Years ; }, } @article {pmid34264726, year = {2021}, author = {Jones, PM and Mitchell, CJ and Wills, AJ and Spicer, SG}, title = {Similarities and differences: Comment on Chan et al. (2021).}, journal = {Journal of experimental psychology. Animal learning and cognition}, volume = {47}, number = {2}, pages = {216-217}, doi = {10.1037/xan0000277}, pmid = {34264726}, issn = {2329-8464}, mesh = {*Cues ; Humans ; *Learning ; }, abstract = {Spicer et al. (2020) reported a series of causal learning experiments in which participants appeared to learn most readily about cues when they were not certain of their causal status and proposed that their results were a consequence of participants' use of theory protection. In the present issue, Chan et al. (2021) present an alternative view, using a modification of Rescorla and Wagner's (1972) influential model of learning. Although the explanation offered by Chan et al. appears very different from that suggested by Spicer et al., there are conceptual commonalities. Here we briefly discuss the similarities and differences of the 2 approaches and agree with Chan et al.'s proposal that the best way to advance the debate will be to test situations in which the 2 theories make differing predictions. (PsycInfo Database Record (c) 2021 APA, all rights reserved).}, } @article {pmid34262508, year = {2021}, author = {Yang, YC and Karmol, AM and Stocco, A}, title = {Core Cognitive Mechanisms Underlying Syntactic Priming: A Comparison of Three Alternative Models.}, journal = {Frontiers in psychology}, volume = {12}, number = {}, pages = {662345}, pmid = {34262508}, issn = {1664-1078}, support = {CDP 13-003/HX/HSRD VA/United States ; }, abstract = {Syntactic priming (SP) is the effect by which, in a dialogue, the current speaker tends to re-use the syntactic constructs of the previous speakers. SP has been used as a window into the nature of syntactic representations within and across languages. Because of its importance, it is crucial to understand the mechanisms behind it. Currently, two competing theories exist. According to the transient activation account, SP is driven by the re-activation of declarative memory structures that encode structures. According to the error-based implicit learning account, SP is driven by prediction errors while processing sentences. By integrating both transient activation and associative learning, Reitter et al.'s hybrid model 2011 assumes that SP is achieved by both mechanisms, and predicts a priming enhancement for rare or unusual constructions. Finally, a recently proposed account, the reinforcement learning account, claims that SP driven by the successful application of procedural knowledge will be reversed when the prime sentence includes grammatical errors. These theories make different assumptions about the representation of syntactic rules (declarative vs. procedural) and the nature of the mechanism that drives priming (frequency and repetition, attention, and feedback signals, respectively). To distinguish between these theories, they were all implemented as computational models in the ACT-R cognitive architecture, and their specific predictions were examined through grid-search computer simulations. Two experiments were then carried out to empirically test the central prediction of each theory as well as the individual fits of each participant's responses to different parameterizations of each model. The first experiment produced results that were best explained by the associative account, but could also be accounted for by a modified reinforcement model with a different parsing algorithm. The second experiment, whose stimuli were designed to avoid the parsing ambiguity of the first, produced somewhat weaker effects. Its results, however, were also best predicted by the model implementing the associative account. We conclude that the data overall points to SP being due to prediction violations that direct attentional resources, in turn suggesting a declarative rather than a RL based procedural representation of syntactic rules.}, } @article {pmid34255604, year = {2022}, author = {Berkowitz, SR and Garrett, BL and Fenn, KM and Loftus, EF}, title = {Eyewitness confidence may not be ready for the courts: a reply to Wixted et al.}, journal = {Memory (Hove, England)}, volume = {30}, number = {1}, pages = {75-76}, doi = {10.1080/09658211.2021.1952271}, pmid = {34255604}, issn = {1464-0686}, mesh = {Awareness ; Emotions ; Humans ; *Memory ; *Mental Recall ; Police ; }, abstract = {Wixted et al. (in press. Doing right by the eyewitness evidence: A response to Berkowitz et al. Memory) remind us that they are aware of some conditions in which confidence does not trump all but suggest that initial high-confidence errors should be rare. In this reply, we draw attention to new lab research that continues to cast doubt on the value of an initial eyewitness identification made with high confidence. Additional data from field studies of police lineups lead us to conclude that it is far too risky in real-world cases to assume that eyewitnesses who have high initial confidence are also highly accurate. As a final point, we dispute Wixted et al.'s interpretation of "initial low confidence" in the DNA exoneration cases.}, } @article {pmid34254592, year = {2021}, author = {Kapica, Ł and Baka, Ł}, title = {[What is job crafting? Review of theoretical models of job crafting].}, journal = {Medycyna pracy}, volume = {72}, number = {4}, pages = {423-436}, doi = {10.13075/mp.5893.01115}, pmid = {34254592}, issn = {2353-1339}, mesh = {Humans ; *Job Satisfaction ; *Models, Theoretical ; }, abstract = {In recent years, there has been a clear increase in the interest in positive phenomena in work psychology. One of such issues is employee-initiated behavior aimed at transforming working conditions in order to increase job satisfaction and match it to one's needs and abilities. These behaviors are referred to as job crafting. With the development of research on this issue, different theoretical concepts and definitions of job crafting were created and then evolved. The aim of the work is to systematize them and perform a critical analysis. The article analyzes 5 theoretical models of job crafting: Wrzesniewski and Dutton's model, Tims and Bakker's model, Zhang and Parker's model, Bindl et al.'s model, and Kooij et al.'s model The publication presents the differences between these models, and strengths and critical points of each of them. Med Pr. 2021;72(4):423-36.}, } @article {pmid34245112, year = {2021}, author = {Livingston, LA and Shah, P and White, SJ and Happé, F}, title = {Further developing the Frith-Happé animations: A quicker, more objective, and web-based test of theory of mind for autistic and neurotypical adults.}, journal = {Autism research : official journal of the International Society for Autism Research}, volume = {14}, number = {9}, pages = {1905-1912}, doi = {10.1002/aur.2575}, pmid = {34245112}, issn = {1939-3806}, support = {/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Adult ; *Autism Spectrum Disorder ; *Autistic Disorder ; Humans ; Intelligence Tests ; Internet ; *Theory of Mind ; }, abstract = {The Frith-Happé Animations Test, depicting interactions between triangles, is widely used to measure theory of mind (ToM) ability in autism spectrum disorder (ASD). This test began with recording, transcribing, and subjectively scoring participants' verbal descriptions, which consistently found ToM-specific difficulties in ASD. More recently in 2011, White et al. created a more objective version of this ToM test using multiple-choice questions. However, there has been surprisingly little uptake of this test, hence it is currently unclear if White et al.'s findings replicate. Further, the lack of an online version of the test may be hampering its use in large-scale studies and outside of research settings. Addressing these issues, we report the development of a web-based version of the Frith-Happé Animations Test for autistic and neurotypical adults. An online version of the test was developed in a large general population sample (study 1; N = 285) and online data were compared with those collected in a lab-based setting (study 2; N = 339). The new online test was then administered to adults with a clinical diagnosis of ASD and matched neurotypical controls (study 3; N = 231). Results demonstrated that the test could successfully be administered online to autistic adults, who showed ToM difficulties compared to neurotypical adults, replicating White et al.'s findings. Overall, we have developed a quicker, more objective, and web-based version of the Frith-Happé Animations Test that will be useful for social cognition research within and beyond the field of autism, with potential utility for clinical settings. LAY SUMMARY: Many autistic people find it hard to understand what other people are thinking. There are many tests for this 'mentalising' ability, but they often take a long time to complete and cannot be used outside of research settings. In 2011, scientists used short silent animations of moving shapes to create a fast way to measure mentalising ability. We developed this into an online test to use in research and clinics to measure mentalising ability in autism.}, } @article {pmid34243911, year = {2021}, author = {McInally, W and Gray-Brunton, C and Chouliara, Z and Kyle, RG}, title = {Experiences of living with cancer of adolescents and young adults and their families: A narrative review and synthesis.}, journal = {Enfermeria clinica}, volume = {31}, number = {4}, pages = {234-246}, doi = {10.1016/j.enfcle.2020.12.005}, pmid = {34243911}, issn = {2445-1479}, mesh = {Adolescent ; Humans ; *Neoplasms/therapy ; Qualitative Research ; Young Adult ; }, abstract = {INTRODUCTION: Adolescence is a critical life stage marked by significant physical, psychological, and social change. Cancer diagnosis during adolescence profoundly affects this experience for adolescents and young adults (AYA) and their families with an impact that continues throughout life. It is important to understand these experiences to ensure delivery of appropriate and high-quality supportive care. This narrative review critically appraised and synthesised qualitative literature that explored the experiences of AYAs and their families living with cancer.

METHOD: Narrative review and synthesis of qualitative research of AYAs' and their families' experiences of cancer. MEDLINE, CINAHL and PsycINFO were searched between February 2000 and September 2019 using search terms including "adolescent", "young people", "young adult", "cancer", "family", and "qualitative". Literature was appraised and synthesised using Popay et al.'s[1] framework.

RESULTS: 3016 articles were retrieved (Medline n=1298, CINAHL n=1632, PsycINFO n=86). Of these, 151 duplicates were removed. 2865 papers were screened with 121 abstracts considered for eligibility for inclusion. Eighteen papers met the inclusion criteria. Three inter-related themes were identified: being diagnosed with cancer; uncertainty - holding on to life and gaps in care delivery.

Few studies discuss the impact of cancer on the families of AYA living with cancer. Future research should explore this experience. By doing so the relational impact of cancer will be better understood as the basis of supportive family-centred care. PROSPERO Registration: CRD42017084148.}, } @article {pmid34238256, year = {2021}, author = {Fisher, L and Dahal, M and Hawkes, S and Puri, M and Buse, K}, title = {Barriers and opportunities to restricting marketing of unhealthy foods and beverages to children in Nepal: a policy analysis.}, journal = {BMC public health}, volume = {21}, number = {1}, pages = {1351}, pmid = {34238256}, issn = {1471-2458}, support = {MR/P025188/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Beverages ; Child ; *Food ; Humans ; *Marketing ; Nepal ; Policy Making ; }, abstract = {BACKGROUND: Marketing of foods and non-alcoholic beverages high in saturated fats, trans-fatty acids, free sugars, or salt ("unhealthy foods") to children is contributing to increasing child obesity. However, many countries have not implemented WHO recommendations to restrict marketing of unhealthy foods to children. We sought to understand the absence of marketing restrictions and identify potential strategic actions to develop and implement such restrictions in Nepal.

METHODS: Eighteen semi-structured interviews were conducted. Thematic analysis was based on Baker et al.'s 18 factor-framework for understanding what drives political commitment to nutrition, organised by five categories: Actors; Institutions; Political and societal contexts; Knowledge, evidence and framing; Capacities and resources.

RESULTS: All factors in Baker et al.'s framework were reported to be acting largely as barriers to Nepal developing and implementing marketing restrictions. Six factors were identified by the highest number of respondents: the threat of private sector interference in policy-making; lack of international actor support; absence of well-designed and enacted policies and legislation; lack of political commitment to regulate; insufficient mobilisation of existing evidence to spur action and lack of national evidence to guide regulatory design; and weak implementation capacity. Opportunities for progress were identified as Nepal's ability to combat private sector interference - as previously demonstrated in tobacco control.

CONCLUSIONS: This is the first study conducted in Nepal examining the lack of restrictions on marketing unhealthy foods to children. Our findings reflect the manifestation of power in the policy process. The absence of civil society and a multi-stakeholder coalition demanding change on marketing of unhealthy food to children, the threat of private sector interference in introducing marketing restrictions, the promotion of norms and narratives around modernity, consumption and the primary role of the individual in regulating diet - all have helped create a policy vacuum on marketing restrictions. We propose that stakeholders focus on five strategic actions, including: developing a multi-stakeholder coalition to put and keep marketing restrictions on the health agenda; framing the need for marketing restrictions as critical to protect child rights and government regulation as the solution; and increasing support, particularly through developing more robust global policy guidance.}, } @article {pmid34232837, year = {2021}, author = {Srivastava, DK and George, EO and Lu, Z and Rai, SN}, title = {Impact of unequal censoring and insufficient follow-up on comparing survival outcomes: Applications to clinical studies.}, journal = {Statistical methods in medical research}, volume = {30}, number = {9}, pages = {2057-2074}, pmid = {34232837}, issn = {1477-0334}, support = {P30 ES030283/ES/NIEHS NIH HHS/United States ; P20 GM113226/GM/NIGMS NIH HHS/United States ; P20 GM125504/GM/NIGMS NIH HHS/United States ; R01 ES029846/ES/NIEHS NIH HHS/United States ; U54 HL120163/HL/NHLBI NIH HHS/United States ; P30 GM127607/GM/NIGMS NIH HHS/United States ; P30 CA021765/CA/NCI NIH HHS/United States ; R01 ES027778/ES/NIEHS NIH HHS/United States ; P20 GM135004/GM/NIGMS NIH HHS/United States ; R35 ES028373/ES/NIEHS NIH HHS/United States ; P42 ES023716/ES/NIEHS NIH HHS/United States ; }, mesh = {Computer Simulation ; *Follow-Up Studies ; Humans ; Proportional Hazards Models ; Survival Analysis ; }, abstract = {Clinical trials with survival endpoints are typically designed to enroll patients for a specified number of years, (usually 2-3 years) with another specified duration of follow-up (usually 2-3 years). Under this scheme, patients who are alive or free of the event of interest at the termination of the study are censored. Consequently, a patient may be censored due to insufficient follow-up duration or due to being lost to follow-up. Potentially, this process could lead to unequal censoring in the treatment arms and lead to inaccurate and adverse conclusions about treatment effects. In this article, using extensive simulation studies, we assess the impact of such censorings on statistical procedures (the generalized logrank tests) for comparing two survival distributions and illustrate our observations by revisiting Mukherjee et al.'s[1] findings of cardiovascular events in patients who took Rofecoxib (Vioxx).}, } @article {pmid34227939, year = {2021}, author = {van der Plas, MJ and Cai, J and Petrlova, J and Saleh, K and Kjellström, S and Schmidtchen, A}, title = {Method development and characterisation of the low-molecular-weight peptidome of human wound fluids.}, journal = {eLife}, volume = {10}, number = {}, pages = {}, pmid = {34227939}, issn = {2050-084X}, support = {LF18020//LEO Fondet/ ; 2017-02341//Swedish Research Council/ ; 2011.0037//Knut and Alice Wallenberg Foundation/ ; 2020-02016//Swedish Research Council/ ; }, mesh = {Body Fluids/*metabolism ; Humans ; Mass Spectrometry/*methods ; Molecular Weight ; Peptide Fragments/*analysis ; Proteomics/*methods ; Staphylococcal Infections/*physiopathology ; Staphylococcus aureus/physiology ; Wound Healing/*physiology ; }, abstract = {The normal wound healing process is characterised by proteolytic events, whereas infection results in dysfunctional activations by endogenous and bacterial proteases. Peptides, downstream reporters of these proteolytic actions, could therefore serve as a promising tool for diagnosis of wounds. Using mass-spectrometry analyses, we here for the first time characterise the peptidome of human wound fluids. Sterile post-surgical wound fluids were found to contain a high degree of peptides in comparison to human plasma. Analyses of the peptidome from uninfected healing wounds and Staphylococcus aureus -infected wounds identify unique peptide patterns of various proteins, including coagulation and complement factors, proteases, and antiproteinases. Together, the work defines a workflow for analysis of peptides derived from wound fluids and demonstrates a proof-of-concept that such fluids can be used for analysis of qualitative differences of peptide patterns from larger patient cohorts, providing potential biomarkers for wound healing and infection.}, } @article {pmid34225842, year = {2021}, author = {Watson, JA and Ndila, CM and Uyoga, S and Macharia, A and Nyutu, G and Mohammed, S and Ngetsa, C and Mturi, N and Peshu, N and Tsofa, B and Rockett, K and Leopold, S and Kingston, H and George, EC and Maitland, K and Day, NP and Dondorp, AM and Bejon, P and Williams, TN and Holmes, CC and White, NJ}, title = {Improving statistical power in severe malaria genetic association studies by augmenting phenotypic precision.}, journal = {eLife}, volume = {10}, number = {}, pages = {}, pmid = {34225842}, issn = {2050-084X}, support = {G0600230/MRC_/Medical Research Council/United Kingdom ; G0801439/MRC_/Medical Research Council/United Kingdom ; 206194/WT_/Wellcome Trust/United Kingdom ; WT077383/Z/05/Z/WT_/Wellcome Trust/United Kingdom ; 204911/Z/16/Z/WT_/Wellcome Trust/United Kingdom ; G0601027/MRC_/Medical Research Council/United Kingdom ; MC_UP_A390_1107/MRC_/Medical Research Council/United Kingdom ; MC_UU_00004/05/MRC_/Medical Research Council/United Kingdom ; 202800/Z/16/Z/WT_/Wellcome Trust/United Kingdom ; G0600718/MRC_/Medical Research Council/United Kingdom ; MC_UU_12023/26/MRC_/Medical Research Council/United Kingdom ; 093956/Z/10/C/WT_/Wellcome Trust/United Kingdom ; 090770/Z/09/Z/WT_/Wellcome Trust/United Kingdom ; MR/M006212/1/MRC_/Medical Research Council/United Kingdom ; 209265/Z/17/Z/WT_/Wellcome Trust/United Kingdom ; 203141/Z/16/Z/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Adolescent ; Adult ; Case-Control Studies ; Child ; Child, Preschool ; Extracellular Matrix Proteins/genetics ; Female ; *Genome-Wide Association Study ; Genomics ; Humans ; Kenya ; *Malaria/diagnosis/epidemiology ; Malaria, Falciparum ; Male ; *Phenotype ; Polymorphism, Genetic ; }, abstract = {Severe falciparum malaria has substantially affected human evolution. Genetic association studies of patients with clinically defined severe malaria and matched population controls have helped characterise human genetic susceptibility to severe malaria, but phenotypic imprecision compromises discovered associations. In areas of high malaria transmission, the diagnosis of severe malaria in young children and, in particular, the distinction from bacterial sepsis are imprecise. We developed a probabilistic diagnostic model of severe malaria using platelet and white count data. Under this model, we re-analysed clinical and genetic data from 2220 Kenyan children with clinically defined severe malaria and 3940 population controls, adjusting for phenotype mis-labelling. Our model, validated by the distribution of sickle trait, estimated that approximately one-third of cases did not have severe malaria. We propose a data-tilting approach for case-control studies with phenotype mis-labelling and show that this reduces false discovery rates and improves statistical power in genome-wide association studies.}, } @article {pmid34216191, year = {2021}, author = {Park, EJ and Jo, M and Park, M and Kang, SJ}, title = {Advance care planning for older adults in community-based settings: An umbrella review.}, journal = {International journal of older people nursing}, volume = {16}, number = {5}, pages = {e12397}, doi = {10.1111/opn.12397}, pmid = {34216191}, issn = {1748-3743}, support = {//Konkuk University/ ; }, mesh = {Aged ; Humans ; *Advance Care Planning ; Communication ; Palliative Care ; Systematic Reviews as Topic ; *Terminal Care ; }, abstract = {BACKGROUND: Advance care planning (ACP) is critical to ensure better quality end of life care, and older adults are often a target of ACP. However, ACP interventions and their outcomes are neither standardised nor conclusive.

OBJECTIVES: To synthesise existing ACP systematic reviews and identify the types and outcomes of ACP interventions for older adults in community-based settings.

METHODS: An umbrella review of systematic reviews. The Joanna Briggs Institute Reviewer's Manual was followed. Relevant systematic reviews were searched by utilising bibliographic databases, grey literature sources, and manual searches between April and July, 2019. Nine systematic reviews met the inclusion criteria. Critical appraisal on the selected reviews was conducted. Data were independently extracted using a data extraction tool by two researchers and synthesised based on consensus.

RESULTS: The systematic reviews suggest the critical features of ACP interventions for older adults in community-based settings including clinicians' face-to-face communication with patients and their family members, comprehensive and individualized decisional aids, a proper intensity of ACP interventions, and professional training. When categorising ACP outcomes according to Sudore et al.'s (Journal of Pain and Symptom Management, 55, 2018, 245) framework, action outcomes (e.g., documentation, discussion) were frequently measured with positive outcomes. Quality of care outcomes such as congruence with care preference and healthcare outcomes such as health status were not reported sufficiently.

CONCLUSIONS: The reviews suggested essential features of ACP interventions, which were often omitted in ACP interventions for older adults. Although the outcomes were generally positive, it is inconclusive as to whether ACP interventions eventually improved quality of end of life care or health status of older adults in community-based settings.

IMPLICATIONS FOR PRACTICE: For ACP interventions to be effective and comparable in their outcomes, we recommend adopting the key intervention components identified in this study. As the effects of ACP interventions are inconclusive, further investigations are warranted.}, } @article {pmid34214217, year = {2021}, author = {Wang, XJ and Murphy, B and Breen-Lyles, M and Fox, J}, title = {Response to Oliviero et al.'s publication: "Impact of COVID-19 lockdown on symptoms in patients with functional gastrointestinal disorders: Relationship with anxiety and perceived stress".}, journal = {Neurogastroenterology and motility}, volume = {33}, number = {11}, pages = {e14207}, pmid = {34214217}, issn = {1365-2982}, mesh = {Anxiety ; *COVID-19 ; Communicable Disease Control ; Depression ; *Gastrointestinal Diseases ; Humans ; SARS-CoV-2 ; Stress, Psychological ; }, } @article {pmid34206725, year = {2021}, author = {Donegan, C and Chun, Y and Griffith, DA}, title = {Modeling Community Health with Areal Data: Bayesian Inference with Survey Standard Errors and Spatial Structure.}, journal = {International journal of environmental research and public health}, volume = {18}, number = {13}, pages = {}, pmid = {34206725}, issn = {1660-4601}, mesh = {*Air Pollution/analysis ; Bayes Theorem ; Female ; Humans ; Male ; Middle Aged ; *Public Health ; Reproducibility of Results ; Surveys and Questionnaires ; United States ; }, abstract = {Epidemiologists and health geographers routinely use small-area survey estimates as covariates to model areal and even individual health outcomes. American Community Survey (ACS) estimates are accompanied by standard errors (SEs), but it is not yet standard practice to use them for evaluating or modeling data reliability. ACS SEs vary systematically across regions, neighborhoods, socioeconomic characteristics, and variables. Failure to consider probable observational error may have substantial impact on the large bodies of literature relying on small-area estimates, including inferential biases and over-confidence in results. The issue is particularly salient for predictive models employed to prioritize communities for service provision or funding allocation. Leveraging the tenets of plausible reasoning and Bayes' theorem, we propose a conceptual framework and workflow for spatial data analysis with areal survey data, including visual diagnostics and model specifications. To illustrate, we follow Krieger et al.'s (2018) call to routinely use the Index of Concentration at the Extremes (ICE) to monitor spatial inequalities in health and mortality. We construct and examine SEs for the ICE, use visual diagnostics to evaluate our observational error model for the ICE, and then estimate an ICE-mortality gradient by incorporating the latter model into our model of sex-specific, midlife (ages 55-64), all-cause United States county mortality rates. We urge researchers to consider data quality as a criterion for variable selection prior to modeling, and to incorporate data reliability information into their models whenever possible.}, } @article {pmid34205425, year = {2021}, author = {Bandy, A and Tantry, B}, title = {ESBL Activity, MDR, and Carbapenem Resistance among Predominant Enterobacterales Isolated in 2019.}, journal = {Antibiotics (Basel, Switzerland)}, volume = {10}, number = {6}, pages = {}, pmid = {34205425}, issn = {2079-6382}, abstract = {Antimicrobial-resistance in Enterobacterales is a serious concern in Saudi Arabia. The present study retrospectively analyzed the antibiograms of Enterobacterales identified from 1 January 2019 to 31 December 2019 from a referral hospital in the Aljouf region of Saudi Arabia. The revised document of the Centers for Disease Control (CDC) CR-2015 and Magiorakos et al.'s document were used to define carbapenem resistance and classify resistant bacteria, respectively. The association of carbapenem resistance, MDR, and ESBL with various sociodemographic characteristics was assessed by the chi-square test and odds ratios. In total, 617 Enterobacterales were identified. The predominant (n = 533 (86.4%)) isolates consisted of 232 (37.6%), 200 (32.4%), and 101 (16.4%) Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis, respectively. In general, 432 (81.0%) and 128 (24.0%) isolates were of MDR and ESBL, respectively. The MDR strains were recovered in higher frequency from intensive care units (OR = 3.24 (1.78-5.91); p < 0.01). E. coli and K. pneumoniae resistance rates to imipenem (2.55 (1.21-5.37); p < 0.01) and meropenem (2.18 (1.01-4.67); p < 0.04), respectively, were significantly higher in winter. The data emphasize that MDR isolates among Enterobacterales are highly prevalent. The studied Enterobacterales exhibited seasonal variation in antimicrobial resistance rates towards carbapenems and ESBL activity.}, } @article {pmid34195934, year = {2022}, author = {Schweppe, J and Schütte, F and Machleb, F and Hellfritsch, M}, title = {Syntax, morphosyntax, and serial recall: How language supports short-term memory.}, journal = {Memory & cognition}, volume = {50}, number = {1}, pages = {174-191}, pmid = {34195934}, issn = {1532-5946}, mesh = {Comprehension ; Humans ; *Language ; *Memory, Short-Term ; Mental Recall ; Semantics ; }, abstract = {In the classic view of verbal short-term memory, immediate recall is achieved by maintaining phonological representations, while the influence of other linguistic information is negligible. According to language-based accounts, short-term retention of verbal material is inherently bound to language production and comprehension, thus also influenced by semantic or syntactic factors. In line with this, serial recall is better when lists are presented in a canonical word order for English rather than in a noncanonical order (e.g., when adjectives precede nouns rather than vice versa; Perham et al., 2009, Quarterly Journal of Experimental Psychology, 62[7], 1285-1293). However, in many languages, grammaticality is not exclusively determined by word order. In German, an adjective-noun sequence is grammatical only if the adjective is inflected in congruence with the noun's person, number, and grammatical gender. Therefore, we investigated whether similar effects of syntactic word order occur in German. In two modified replications of Perham et al.'s study, we presented lists of three pairs of adjectives and nouns, presented in adjective-noun or in noun-adjective order. In addition, we manipulated morphosyntactic congruence between nouns and adjectives within pairs (Exp. 1: congruently inflected vs. uninflected adjectives; Exp. 2: congruently inflected vs. incongruently inflected adjectives). Both experiments show an interaction: Word order affected recall performance only when adjectives were inflected in congruence with the corresponding noun. These findings are in line with language-based models and indicate that, in a language that determines grammaticality in an interplay of syntactic and morphosyntactic factors, word order alone is not sufficient to improve verbal short-term memory.}, } @article {pmid34182987, year = {2021}, author = {Toben, D and Mak-van der Vossen, M and Wouters, A and Kusurkar, RA}, title = {Validation of the professional identity questionnaire among medical students.}, journal = {BMC medical education}, volume = {21}, number = {1}, pages = {359}, pmid = {34182987}, issn = {1472-6920}, mesh = {Factor Analysis, Statistical ; Humans ; Psychometrics ; Reproducibility of Results ; Social Identification ; *Students, Medical ; Surveys and Questionnaires ; }, abstract = {BACKGROUND: Professionalism represents a cornerstone of the medical profession, prompting medical educators to actively develop instruments to measure professional identity formation among medical students. A quantitative approach to this problem has been lacking. Hence in this study, we investigate the validity and reliability of using Brown et al.'s [1986] Professional Identity Questionnaire (PIQ) to measure professional identity among medical students.

METHODS: We used the American Psychological Association's account of validity and reliability to examine the PIQ in terms of its internal structure, its relation to a validated motivation scale, its content, and its internal consistency. To this end, we performed two factor analyses, a Pearson's correlation test, an expert evaluation and measured Cronbach's alpha, respectively..

RESULTS: Factor analysis revealed two latent factors underlying the items of the PIQ. We found a negative to positive spectrum of Pearson's correlations corresponding to increasingly internal qualities of motivation. Experts unanimously rated four out of ten of the PIQ's items as relevant, reliability analysis yielded a Cronbach's alpha value of 0.82.

CONCLUSION: Despite poor ratings by experts in the field, these results illustrate the PIQ as a valid and reliable quantitative measure of medical students' professional identity; its two factors reflecting the measure of attached and detached attitudes towards the medical profession. Educators may use the instrument as a tool for monitoring PIF among their students, as well as for designing and evaluating their medical curriculum. Future research might build on the current findings by investigating other dimensions of the PIQ's validity, including response process validity, predictive validity and consequential validity.}, } @article {pmid34178910, year = {2021}, author = {Ferschl, S and Till, M and Abu-Omar, K and Pfeifer, K and Gelius, P}, title = {Scientific Cooperation and the Co-production of Scientific Outcomes for Physical Activity Promotion: Results From a Transdisciplinary Research Consortium.}, journal = {Frontiers in public health}, volume = {9}, number = {}, pages = {604855}, pmid = {34178910}, issn = {2296-2565}, mesh = {Exercise ; Germany ; Humans ; *Interdisciplinary Research ; *Research Personnel ; }, abstract = {Background: To tackle complex societal challenges such as the high prevalence of physical inactivity, research funding is increasingly channeled toward cross-disciplinary research consortia. This study focused on exchange and cooperation (E&C) among the scientists of a 5-year transdisciplinary research initiative in Germany. Researchers' perceptions of E&C were combined with numbers of collaborative products during the project's life to make the developments of E&C and the quality of collaborative products visible. Methods: We applied a mixed-methods design including a qualitative content analysis of pre-interviews, focus-group interviews, and documents as well as a quantitative analysis of research (scientific publications, books, conference participations) and training outcomes (supervised bachelor's, master's, and Ph.D. theses). Inductive and deductive approaches were combined to analyze factors of collaborative readiness and to identify perceptions of E&C among project teams. Based on Hall et al.'s "Conceptual Model for Evaluation of Collaborative Initiatives," the project period was separated into phases of "collaborative readiness," "collaborative capacity," and "collaborative products." Results: Our findings revealed a discrepancy between the objectively assessed concepts of collaborative readiness and researchers' reported perceptions of E&C during the early project stage. A set of E&C hindering factors identified during the initial project phase remained present until the final project stage. Further, E&C among scientists increased over time, as reflected by researchers' perceptions. Reports of scientists also showed that outcomes were co-produced at the final project stage for the first time, while knowledge integration had not yet been achieved. Generally, the number of collaborative products (particularly scientific publications) also substantially increased over time. E&C was supported and promoted by the efforts of the coordinating sub-project. Conclusion: Scientific E&C is a learning process and needs time to develop. A participatory research approach taking into account the perspectives on and requirements for E&C during the project's design might lay the ground for suitable, supportive, and transparent conditions for effective and successful E&C. Despite their time- and resource-consuming nature, cross-disciplinary research initiatives provide a fertile context in which to generate new solutions for pressing societal issues given that long-term funding and the establishment of an overarching coordination organ is assured.}, } @article {pmid34178101, year = {2021}, author = {Morrissey, MB and Hubbs, A and Festa-Bianchet, M}, title = {Horn growth appears to decline under intense trophy hunting, but biases in hunt data challenge the interpretation of the evolutionary basis of trends.}, journal = {Evolutionary applications}, volume = {14}, number = {6}, pages = {1519-1527}, pmid = {34178101}, issn = {1752-4571}, abstract = {A recent article in Evolutionary Applications by LaSharr et al. reports on trends in the size of horns of bighorn sheep (Ovis canadensis) throughout much of the species' range. The article concludes that there are "... stable or increasing trends in horn growth over nearly 3 decades in the majority of hunt areas throughout the western U.S. and Canada." However, the article equates nonsignificance of predominantly negative trends in the areas with the most selective harvest as evidence for the null hypothesis of no trends and also fails to consider well-known and serious biases in the use of data collected in size-regulated hunts. By applying meta-analysis to the estimates reported by LaSharr et al., we show that there has been a pervasive overall trend of declining horn sizes in Alberta, where the combination of horn size-based legality, combined with unrestricted hunter numbers are understood to generate the greatest selective pressures. Given the nature of the biases in the underlying data, the magnitudes of the trends resulting from our re-analysis of LaSharr et al.'s (Evolutionary Applications, 2019, 12, 1823) trend estimates are probably underestimated.}, } @article {pmid34174834, year = {2021}, author = {Haley, AD and Powell, BJ and Walsh-Bailey, C and Krancari, M and Gruß, I and Shea, CM and Bunce, A and Marino, M and Frerichs, L and Lich, KH and Gold, R}, title = {Strengthening methods for tracking adaptations and modifications to implementation strategies.}, journal = {BMC medical research methodology}, volume = {21}, number = {1}, pages = {133}, pmid = {34174834}, issn = {1471-2288}, support = {R18 DK114701/DK/NIDDK NIH HHS/United States ; K01 MH113806/MH/NIMH NIH HHS/United States ; P50 CA244289/CA/NCI NIH HHS/United States ; }, mesh = {*Delivery of Health Care ; Humans ; *Implementation Science ; }, abstract = {BACKGROUND: Developing effective implementation strategies requires adequate tracking and reporting on their application. Guidelines exist for defining and reporting on implementation strategy characteristics, but not for describing how strategies are adapted and modified in practice. We built on existing implementation science methods to provide novel methods for tracking strategy modifications.

METHODS: These methods were developed within a stepped-wedge trial of an implementation strategy package designed to help community clinics adopt social determinants of health-related activities: in brief, an 'Implementation Support Team' supports clinics through a multi-step process. These methods involve five components: 1) describe planned strategy; 2) track its use; 3) monitor barriers; 4) describe modifications; and 5) identify / describe new strategies. We used the Expert Recommendations for Implementing Change taxonomy to categorize strategies, Proctor et al.'s reporting framework to describe them, the Consolidated Framework for Implementation Research to code barriers / contextual factors necessitating modifications, and elements of the Framework for Reporting Adaptations and Modifications-Enhanced to describe strategy modifications.

RESULTS: We present three examples of the use of these methods: 1) modifications made to a facilitation-focused strategy (clinics reported that certain meetings were too frequent, so their frequency was reduced in subsequent wedges); 2) a clinic-level strategy addition which involved connecting one study clinic seeking help with community health worker-related workflows to another that already had such a workflow in place; 3) a study-level strategy addition which involved providing assistance in overcoming previously encountered (rather than de novo) challenges.

CONCLUSIONS: These methods for tracking modifications made to implementation strategies build on existing methods, frameworks, and guidelines; however, as none of these were a perfect fit, we made additions to several frameworks as indicated, and used certain frameworks' components selectively. While these methods are time-intensive, and more work is needed to streamline them, they are among the first such methods presented to implementation science. As such, they may be used in research on assessing effective strategy modifications and for replication and scale-up of effective strategies. We present these methods to guide others seeking to document implementation strategies and modifications to their studies.

TRIAL REGISTRATION: clinicaltrials.gov ID: NCT03607617 (first posted 31/07/2018).}, } @article {pmid34163812, year = {2020}, author = {Ashuiev, A and Allouche, F and Wili, N and Searles, K and Klose, D and Copéret, C and Jeschke, G}, title = {Molecular and supported Ti(iii)-alkyls: efficient ethylene polymerization driven by the π-character of metal-carbon bonds and back donation from a singly occupied molecular orbital.}, journal = {Chemical science}, volume = {12}, number = {2}, pages = {780-792}, pmid = {34163812}, issn = {2041-6520}, abstract = {While Ti(iii) alkyl species are the proposed active sites in Ziegler-Natta ethylene polymerization catalysts, the corresponding well-defined homogeneous catalysts are not known. We report that well-defined neutral β-diiminato Ti(iii) alkyl species, namely [Ti(nacnac)(CH2 [t] Bu)2] and its alumina-grafted derivative [(AlsO)Ti(nacnac)(CH2 [t] Bu)], are active towards ethylene polymerization at moderate pressures and temperatures and possess an electron configuration well-adapted to insertion of ethylene. Advanced EPR spectroscopy showed that ethylene insertion into a Ti(iii)-C bond takes place during polymerization from Ti(nacnac)(CH2 [t] Bu)2. A combination of pulsed EPR spectroscopy and DFT calculations, based on a crystal structure of [Ti(nacnac)(CH2 [t] Bu)2], enabled us to reveal details about the structure and electronic configurations of both molecular and surface-grafted species. For both compounds, the α-agostic C-H interaction, which involves the singly occupied molecular orbital, indicates a π character of the metal-carbon bond; this π character is enhanced upon ethylene coordination, leading to a nearly barrier-less C2H4 insertion into Ti(iii)-C bonds after this first step. During coordination, back donation from the SOMO to the π*(C2H4) occurs, leading to stabilization of π-ethylene complexes and to a significant lowering of the overall energy of the C2H4 insertion transition state. In d[1] alkyl complexes, ethylene insertion follows an original "augmented" Cossee-Arlman mechanism that involves the delocalization of unpaired electrons between the SOMO, π*(C2H4) and σ*(Ti-C) in the transition state, which further favors ethylene insertion. All these factors facilitate ethylene polymerization on Ti(iii) neutral alkyl species and make d[1] alkyl complexes potentially more effective polymerization catalysts than their d[0] analogues.}, } @article {pmid34160317, year = {2022}, author = {Körner, R and Röseler, L and Schütz, A}, title = {Commentary on Elkjær et al.'s (2020) Meta-Analysis on Expansive Versus Contractive Nonverbal Displays.}, journal = {Perspectives on psychological science : a journal of the Association for Psychological Science}, volume = {17}, number = {1}, pages = {305-307}, doi = {10.1177/1745691620984474}, pmid = {34160317}, issn = {1745-6924}, abstract = {We offer a critical perspective on the meta-analysis by Elkjær et al. (2020) by pointing out three constraints: The first refers to open-science practices, the second addresses the selection of studies, and the third offers a broader theoretical perspective. We argue that preregistration and adherence to the highest standards of conducting meta-analyses is important. Further, we identified several missing studies. Regarding the theoretical perspective, we suggest that it may be useful to tie body positions into the dominance-prestige framework and, on that basis, to distinguish two types of body positions. Such an approach has the potential to account for discrepancies in previous meta-analytical evidence regarding the effects of expansive versus contractive nonverbal displays. Future research may thus be able to provide not only methodological but also theoretical innovations to the field of body positions.}, } @article {pmid34132193, year = {2021}, author = {McCormick, JW and Russo, MA and Thompson, S and Blevins, A and Reynolds, KA}, title = {Structurally distributed surface sites tune allosteric regulation.}, journal = {eLife}, volume = {10}, number = {}, pages = {}, pmid = {34132193}, issn = {2050-084X}, mesh = {Allosteric Regulation/*genetics ; Allosteric Site/*genetics ; Computational Biology ; Escherichia coli/genetics ; Models, Molecular ; Mutation/genetics ; Protein Binding/*genetics ; Protein Domains/genetics ; Recombinant Fusion Proteins/chemistry/genetics/metabolism ; Tetrahydrofolate Dehydrogenase/chemistry/genetics/metabolism ; }, abstract = {Our ability to rationally optimize allosteric regulation is limited by incomplete knowledge of the mutations that tune allostery. Are these mutations few or abundant, structurally localized or distributed? To examine this, we conducted saturation mutagenesis of a synthetic allosteric switch in which Dihydrofolate reductase (DHFR) is regulated by a blue-light sensitive LOV2 domain. Using a high-throughput assay wherein DHFR catalytic activity is coupled to E. coli growth, we assessed the impact of 1548 viable DHFR single mutations on allostery. Despite most mutations being deleterious to activity, fewer than 5% of mutations had a statistically significant influence on allostery. Most allostery disrupting mutations were proximal to the LOV2 insertion site. In contrast, allostery enhancing mutations were structurally distributed and enriched on the protein surface. Combining several allostery enhancing mutations yielded near-additive improvements to dynamic range. Our results indicate a path toward optimizing allosteric function through variation at surface sites.}, } @article {pmid34121958, year = {2022}, author = {Carey, PAK and Delfabbro, P and King, D}, title = {An Evaluation of Gaming-Related Harms in Relation to Gaming Disorder and Loot Box Involvement.}, journal = {International journal of mental health and addiction}, volume = {20}, number = {5}, pages = {2906-2921}, pmid = {34121958}, issn = {1557-1874}, abstract = {The specific nature of harm and functional impairment in the context of gaming disorder (GD) has received limited attention. In this study, we present one of the first concerted attempts to measure the types and degree of harm experienced by people displaying signs of problem gaming. Attempts were made to assess the extent to which types of harm were attributable to gaming as opposed to other factors. The study also investigated potential behavioural indicators of harmful involvement, including exposure to loot boxes. A sample of 471 regular gamers (M = 380, F = 73), recruited through the online platform Prolific, completed a survey where problem gaming was identified using Petry et al.'s (2014) checklist. Individuals who met the cut-off for gaming disorder scored higher than the non-problem group on most dimensions of harm, with physical and psychological types being the most common issues. Loot box expenditure was low (M = $25 in 3 months, for the 10.8% of respondents who played loot boxes) but significantly positively associated with the degree of gaming-related financial harm. This study shows that problem gaming is most strongly associated with physical or psychological harm and that financial harms may manifest in gaming activities that facilitate continuous spending options.}, } @article {pmid34119525, year = {2021}, author = {Braun, MN and Wessler, J and Friese, M}, title = {A meta-analysis of Libet-style experiments.}, journal = {Neuroscience and biobehavioral reviews}, volume = {128}, number = {}, pages = {182-198}, doi = {10.1016/j.neubiorev.2021.06.018}, pmid = {34119525}, issn = {1873-7528}, mesh = {Consciousness ; Humans ; Intention ; *Neurosciences ; Uncertainty ; *Volition ; }, abstract = {In the seminal Libet experiment (Libet et al., 1983), unconscious brain activity preceded the self-reported, conscious intention to move. This was repeatedly interpreted as challenging the view that (conscious) mental states cause behavior and, prominently, as challenging the existence of free will. Extensive discussions in philosophy, psychology, neuroscience, and jurisprudence followed, but further empirical findings were heterogeneous. However, a quantitative review of the literature summarizing the evidence of Libet-style experiments is lacking. The present meta-analysis fills this gap. The results revealed a temporal pattern that is largely consistent with the one found by Libet and colleagues. Remarkably, there were only k = 6 studies for the time difference between unconscious brain activity and the conscious intention to move - the most crucial time difference regarding implications about conscious causation and free will. Additionally, there was a high degree of uncertainty associated with this meta-analytic effect. We conclude that some of Libet et al.'s findings appear more fragile than anticipated in light of the substantial scientific work that built on them.}, } @article {pmid34114195, year = {2021}, author = {Wang, L and Ji, C and Kitchen, P and Williams, A}, title = {Social participation and depressive symptoms of carer-employees of older adults in Canada: a cross-sectional analysis of the Canadian Longitudinal Study on Aging.}, journal = {Canadian journal of public health = Revue canadienne de sante publique}, volume = {112}, number = {5}, pages = {927-937}, pmid = {34114195}, issn = {1920-7476}, support = {HWP - 146001//CIHR/SSHRC Healthy Productive Work Partnership Grant/ ; }, mesh = {Aged ; Canada/epidemiology ; *Caregivers/psychology/statistics & numerical data ; Cross-Sectional Studies ; *Depression/epidemiology ; Humans ; Longitudinal Studies ; *Social Participation/psychology ; }, abstract = {OBJECTIVES: This study used two waves of data from the Canadian Longitudinal Study on Aging (CLSA) to investigate the association between social participation and depressive symptoms in carer-employees (CEs) and non-carer-employees (NCEs).

METHODS: Adopting Pearlin et al.'s stress model, multivariate linear regression was used to examine the relationships among carer role, social participation, and depressive symptoms in Canadian employees using the first two waves of CLSA data, while controlling for possible confounders.

RESULTS: Higher levels of social participation were found to be associated with lower depressive symptoms in both waves. Social participation was found to moderate depressive symptoms for CEs when compared with NCEs in Wave 2 but not in Wave 1.

CONCLUSION: The present study highlights the importance of social participation in reducing CEs' depressive symptoms. The findings provide support for innovative policy and intervention efforts to encourage and enhance social participation at work via carer-friendly workplace policies for CEs across Canada.}, } @article {pmid34109872, year = {2023}, author = {Henriksen, L and Kisa, S and Lukasse, M and Flaathen, EM and Mortensen, B and Karlsen, E and Garnweidner-Holme, L}, title = {Cultural Sensitivity in Interventions Aiming to Reduce or Prevent Intimate Partner Violence During Pregnancy: A Scoping Review.}, journal = {Trauma, violence & abuse}, volume = {24}, number = {1}, pages = {97-109}, pmid = {34109872}, issn = {1552-8324}, mesh = {Female ; Pregnancy ; Humans ; United States ; Cultural Competency ; Longitudinal Studies ; *Intimate Partner Violence/prevention & control ; Pregnant People ; *Emigrants and Immigrants ; Randomized Controlled Trials as Topic ; }, abstract = {Intimate partner violence (IPV) around the time of pregnancy is a recognized global health problem. Ethnic minorities and immigrant pregnant women experiencing IPV require culturally responsive health services. The aim of this scoping review was to identify aspects of cultural sensitivity in interventions to prevent or reduce IPV among ethnic minorities and immigrant pregnant women in high-income countries. Eight databases were searched in November 2019. Any type of scientific research, quantitative, qualitative, or mixed methods studies regarding interventions against IPV among pregnant women were considered for inclusion. Resnicow et al.'s definition of cultural sensitivity was used to identify aspects of cultural sensitivity. Ten papers relating to nine interventions/studies met our inclusion criteria. These studies, which included randomized controlled trials, a mixed methods study, a program evaluation, and a longitudinal study, were conducted in Australia, Belgium, Norway, and the United States. Aspects of surface cultural sensitivity, including the translation of intervention content into the language of the target group(s) and the involvement of bilingual staff to recruit participants, were identified in eight studies. Deep structure aspects of cultural sensitivity were identified in one study, where the intervention content was pretested among the target group(s). Results that could be related to the culture-sensitive adaptions included successful recruitment of the target population. Three studies were planning to investigate women's experiences of interventions, but no publications were yet available. This scoping review provides evidence that culturally sensitive interventions to reduce or prevent IPV among immigrant pregnant women are limited in number and detail.}, } @article {pmid34105438, year = {2021}, author = {Ortner, CNM and Grapes, A and Stoney, M}, title = {The effect of temporal goals on emotion regulation choice: a replication and extension.}, journal = {Cognition & emotion}, volume = {35}, number = {6}, pages = {1248-1255}, doi = {10.1080/02699931.2021.1937947}, pmid = {34105438}, issn = {1464-0600}, mesh = {*Emotional Regulation ; Emotions ; *Goals ; Humans ; Motivation ; }, abstract = {To test predictions of the extended process model of emotion regulation, we conducted a pre-registered replication and extension of Sheppes et al.'s Study 3 ([2014]. Emotion regulation choice: A conceptual framework and supporting evidence. Journal of Experimental Psychology: General, 143(1), 163-181. doi:10.1037/a0030831) on the effects of intensity and temporal goal on reappraisal choice. In the original study, participants chose reappraisal over distraction more in response to low intensity stimuli than high intensity stimuli and when given a long-term emotion regulation goal than an immediate emotion regulation goal. We attempted a replication in a larger sample and extended the research to test whether individual differences in the tendency to consider future consequences of one's actions (CFC) would moderate the effect of goal on emotion regulation choice. We replicated the effects of intensity, but not temporal goal, on choice. CFC interacted with temporal goal: participants low in CFC chose reappraisal more often if given a short-term goal than a long-term goal, but participants high in CFC chose reappraisal more often if given a long-term goal than a short-term goal. Although the effects of temporal goal did not replicate, our results suggest that it may interact with individual differences to influence emotion regulation choice. These findings contribute to a growing interest in factors that influence emotion regulation behaviour.}, } @article {pmid34098430, year = {2021}, author = {Hong, W and Liu, RD and Ding, Y and Jiang, S and Yang, X and Sheng, X}, title = {Academic procrastination precedes problematic mobile phone use in Chinese adolescents: A longitudinal mediation model of distraction cognitions.}, journal = {Addictive behaviors}, volume = {121}, number = {}, pages = {106993}, doi = {10.1016/j.addbeh.2021.106993}, pmid = {34098430}, issn = {1873-6327}, mesh = {Adolescent ; *Cell Phone Use ; China/epidemiology ; Cognition ; Cross-Sectional Studies ; Humans ; *Procrastination ; Students ; }, abstract = {Cross-sectional studies have documented a positive association between academic procrastination and problematic mobile phone use (PMPU). However, the specific predictive direction has remained controversial and the potential mechanisms underlying the association have not been rigorously evaluated. According to Davis's cognitive-behavioral model, Brand et al.'s I-PACE model, and procrastination-related theories, academic procrastination and PMPU might have a reciprocal relationship and distraction cognitions might play a mediating role in this process. A total of 633 secondary school students completed three self-report questionnaires at three 6-month intervals over the course of 1.5 years. The cross-lagged panel model results showed that earlier academic procrastination positively predicted subsequent PMPU over time, but the reverse prediction was not stable. Furthermore, distraction cognitions played a mediating role in linking earlier academic procrastination and subsequent PMPU. These findings indicate that academic procrastination precedes PMPU with distraction cognitions as a potential mediator, which contributes to clarifying the controversial relationship and explicating the underlying mechanism. Overall, interventions for academic procrastination may be effective in reducing maladaptive cognitions associated with mobile phones and preventing adolescents from developing PMPU.}, } @article {pmid34096739, year = {2021}, author = {Venkatesh, V and Ganster, DC and Schuetz, SW and Sykes, TA}, title = {Risks and rewards of conscientiousness during the COVID-19 pandemic.}, journal = {The Journal of applied psychology}, volume = {106}, number = {5}, pages = {643-656}, doi = {10.1037/apl0000919}, pmid = {34096739}, issn = {1939-1854}, mesh = {Adult ; COVID-19/epidemiology/*psychology ; Emotional Adjustment ; Female ; Humans ; *Job Satisfaction ; Male ; Motivation ; Occupational Stress/epidemiology/psychology ; Reward ; Risk Factors ; *Teleworking ; *Work Performance ; }, abstract = {Highly conscientious workers are more motivated and productive than their less conscientious colleagues. Moreover, conscientious employees tend to be more satisfied and less stressed from their work. One consequence of the COVID-19 pandemic, however, is that many workers have transitioned to working remotely, often under conditions of less direct supervision and less clarity about expected work activities and outcomes. We proposed that this significant change in work context constitutes a weakening of situational strength that can change the relationship of conscientiousness with job strain, job satisfaction, and job performance. Using Meyer et al.'s (2010) conceptualization of situational strength, we tested the moderating effect of situational strength by surveying 474 white-collar employees in a Fortune-1000 firm in 2019 and again in 2020 after they had all transitioned to working remotely. We found that the changes in work context due to COVID-19 significantly lowered scores on situational strength and this was accompanied by a stronger positive effect of conscientiousness on performance. Importantly, during COVID-19, the relationships of conscientiousness with strain and satisfaction showed a reversal of sign, with more conscientious workers reporting higher strain and lower satisfaction. These effects were partially mediated by job demands and were replicated with work hours. The results provide a test of situational strength theory and suggest that changes in situational strength due to COVID-19 may cause an organization's most conscientious employees to be at elevated risk for burnout and dissatisfaction, and consequently, turnover, if not managed appropriately. (PsycInfo Database Record (c) 2021 APA, all rights reserved).}, } @article {pmid34091409, year = {2021}, author = {Corron, LK and Santos, F and Adalian, P and Chaumoitre, K and Guyomarc'h, P and Marchal, F and Brůžek, J}, title = {How low can we go? A skeletal maturity threshold for probabilistic visual sex estimation from immature human os coxae.}, journal = {Forensic science international}, volume = {325}, number = {}, pages = {110854}, doi = {10.1016/j.forsciint.2021.110854}, pmid = {34091409}, issn = {1872-6283}, mesh = {Adolescent ; Adult ; Age Determination by Skeleton/*methods ; Child ; Epiphyses/*anatomy & histology/diagnostic imaging ; Female ; Forensic Anthropology ; Humans ; Male ; Pelvic Bones/*anatomy & histology/diagnostic imaging ; Sex Determination by Skeleton/*methods ; Tomography, X-Ray Computed ; Young Adult ; }, abstract = {OBJECTIVES: The appearance of sexually dimorphic traits varies depending on the type of bone, age, environmental and genetic factors and is closely linked to skeletal maturation sequence. Subadult sex estimation currently shows inconsistent accuracy and methods do not incorporate indicators of maturation. The goal of this study is to apply the Santos et al. (2019) adult sex estimation method on virtually reconstructed subadult os coxae and account for pelvic maturation.

MATERIAL AND METHODS: The right os coxae of 194 female and male individuals aged 11-30 years from Marseille, France were virtually reconstructed from computed tomography (CT) scans. Santos et al.'s (2019) 11 traits were scored as female, male, or indeterminate. Maturation of 10 pelvic epiphyseal sites was scored using a four-stage system (0-3) to obtain a composite maturity score from 1 to 30.

RESULTS: Three maturity groups were identified based on composite maturity scores ranging from 0 to 30. Individuals with a composite maturity score of 15 or higher showed 98 % sex estimation accuracy and a 6 % indeterminate rate. Scores of 2 for the ischiatic tuberosity or 1 for the anterior superior iliac spine can be used as proxies for a composite maturity score of 15 and application on incomplete bones.

DISCUSSION: Sexual dimorphism was observed in the epiphyseal maturation sequence and the development of sexually dimorphic pelvic traits. The Santos et al. (2019) method is applicable on immature individuals who meet a maturation threshold with comparable accuracy to adults, without relying on known or estimated age.}, } @article {pmid34075724, year = {2021}, author = {Xu, J and Yang, L and Cao, S and Wang, J and Ma, Y and Zhang, J and Lu, X}, title = {Sandwiched Cathodes Assembled from CoS2 -Modified Carbon Clothes for High-Performance Lithium-Sulfur Batteries.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {8}, number = {16}, pages = {e2101019}, pmid = {34075724}, issn = {2198-3844}, support = {51972092//National Natural Science Foundation of China/ ; 51802145//National Natural Science Foundation of China/ ; 2020rcjj11//Hefei Normal University High-Level Talent Research Startup Fund/ ; }, abstract = {Structural design of advanced cathodes is a promising strategy to suppress the shuttle effect for lithium-sulfur batteries (LSBs). In this work, the carbon cloth covered with CoS2 nanoparticles (CC-CoS2) is prepared to function as both three-dimensional (3D) current collector and physicochemical barrier to retard migration of soluble lithium polysulfides. On the one hand, the CC-CoS2 film works as a robust 3D current collector and host with high conductivity, high sulfur loading, and high capability of capturing polysulfides. On the other hand, the 3D porous CC-CoS2 film serves as a multifunctional interlayer that exhibits efficient physical blocking, strong chemisorption, and fast catalytic redox reaction kinetics toward soluble polysulfides. Consequently, the Al@S/AB@CC-CoS2 cell with a sulfur loading of 1.2 mg cm[-2] exhibits a high rate capability (≈823 mAh g[-1] at 4 C) and delivers excellent capacity retention (a decay of ≈0.021% per cycle for 1000 cycles at 4 C). Moreover, the sandwiched cathode of CC-CoS2 @S/AB@CC-CoS2 is designed for high sulfur loading LSBs. The CC-CoS2 @S/AB@CC-CoS2 cells with sulfur loadings of 4.2 and 6.1 mg cm[-2] deliver high reversible capacities of 1106 and 885 mAh g[-1] , respectively, after 100 cycles at 0.2 C. The outstanding electrochemical performance is attributed to the sandwiched structure with active catalytic component.}, } @article {pmid34067062, year = {2021}, author = {Lin, CC and Chaou, CH and Gao, SY}, title = {Influential Factors of Local Tissue Necrosis after Taiwan Cobra Bites: A Secondary Analysis of the Clinical Significance of Venom Detection in Patients of Cobra Snakebites.}, journal = {Toxins}, volume = {13}, number = {5}, pages = {}, pmid = {34067062}, issn = {2072-6651}, mesh = {Adult ; Animals ; Antivenins/*administration & dosage ; Cohort Studies ; Elapid Venoms/*toxicity ; Elapidae ; Female ; Humans ; Male ; Middle Aged ; Necrosis/etiology ; Retrospective Studies ; Snake Bites/*complications/pathology/therapy ; Taiwan ; }, abstract = {Local tissue swelling, inflammation, and wound necrosis are observed in Taiwan cobra bites. Knowledge of the factors influencing local tissue necrosis after cobra bites might improve the cobra bite treatment strategy. Therefore, we aimed to explore the factors influencing local tissue necrosis after cobra bites. This was a retrospective observational cohort study. All patients clinical presentations including serum venom levels for determining the influential factors in this study were obtained from Hung et al.'s previous study. Clinical features, such as bite information, initial swelling, patient presentation time, serum venom levels, and antivenom, use were extracted. The measurement outcome was the development of wound necrosis. The factors influencing wound necrosis were investigated using univariate and logistic regression analyses. The influential factors of local tissue necrosis and their areas under the curve were: initial limb swelling, 0.88; presentation time × serum level, 0.80; initial necrosis, 0.75; patient presentation time, 0.70. Serum venom level alone cannot be used as a predictive factor. The development of tissue necrosis might be associated with the venom factor, time factor, and their interaction. These influential factors can be used in future studies to evaluate antivenom efficacy.}, } @article {pmid34066646, year = {2021}, author = {Lu, TC and Yang, PC and Jana, B}, title = {Improving the Reversible LSB Matching Scheme Based on the Likelihood Re-Encoding Strategy.}, journal = {Entropy (Basel, Switzerland)}, volume = {23}, number = {5}, pages = {}, pmid = {34066646}, issn = {1099-4300}, support = {109-2221-E-324 -025 -MY3//Ministry of Science and Technology, Taiwan/ ; }, abstract = {In 2018, Tseng et al. proposed a dual-image reversible embedding method based on the modified Least Significant Bit matching (LSB matching) method. This method improved on the dual-image LSB matching method proposed by Lu et al. In Lu et al.'s scheme, there are seven situations that cannot be restored and need to be modified. Furthermore, the scheme uses two pixels to conceal four secret bits. The maximum modification of each pixel, in Lu et al.'s scheme, is two. To decrease the modification, Tseng et al. use one pixel to embed two secret bits and allow the maximum modification to decrease from two to one such that the image quality can be improved. This study enhances Tseng et al.'s method by re-encoding the modified rule table based on the probability of each hiding combination. The scheme analyzes the frequency occurrence of each combination and sets the lowest modified codes to the highest frequency case to significantly reduce the amount of modification. Experimental results show that better image quality is obtained using our method under the same amount of hiding payload.}, } @article {pmid34065999, year = {2021}, author = {Zhang, J and Gu, X and Zhang, X and Lee, J and Chang, M and Zhang, T}, title = {Longitudinal Effects of Motivation and Physical Activity on Depressive Symptoms among College Students.}, journal = {International journal of environmental research and public health}, volume = {18}, number = {10}, pages = {}, pmid = {34065999}, issn = {1660-4601}, mesh = {Adolescent ; Adult ; China/epidemiology ; *Depression/epidemiology ; Exercise ; Female ; Humans ; Male ; *Motivation ; Students ; Surveys and Questionnaires ; Universities ; Young Adult ; }, abstract = {High prevalence of depression and physical inactivity have been consistently reported among college students, especially in females. Guided by Lubans et al.'s conceptual framework, the primary purpose of this study was to examine the longitudinal relationships of PA motivation with leisure-time PA and depressive symptoms among college students over one academic year. Employing a longitudinal repeated measure design, 1004 college students in China were recruited in this study (28.3% males and 71.7% females; M age = 18.93 ± 0.64 years; 18-22 years old). Participants completed previously validated questionnaires assessing PA motivation (perceived competence beliefs and task values toward PA), leisure-time PA participation, and depressive symptoms in Fall 2016 (Time 1) and Fall 2017 (Time 2). Both male and female college students showed a significant increase of depressive symptoms from freshmen to sophomores (p < 0.05). The regression models indicated that perceived competence beliefs and task values toward PA were significant predictors of depressive symptoms at Time 2 (p < 0.05) after controlling for Time 1 measures in males and females, respectively. Physically active college students consistently demonstrated higher PA motivation, and they displayed fewer depressive symptoms compared to inactive peers over time (p < 0.05). The findings suggest sex-specified motivational intervention strategies and PA promotion programs/opportunities are needed to reduce depression symptoms among college students over time.}, } @article {pmid34051243, year = {2021}, author = {Khin, YP and Nawa, N and Fujiwara, T and Surkan, PJ}, title = {Access to contraceptive services among Myanmar women living in Japan: A qualitative study.}, journal = {Contraception}, volume = {104}, number = {5}, pages = {538-546}, doi = {10.1016/j.contraception.2021.05.008}, pmid = {34051243}, issn = {1879-0518}, mesh = {Contraception ; *Contraceptive Agents ; Female ; Humans ; Japan ; Myanmar ; Pregnancy ; Qualitative Research ; *Transients and Migrants ; }, abstract = {OBJECTIVES: Despite relatively poor health outcomes of migrants in Japan, little is known about their access to reproductive healthcare. We conducted qualitative research to explore perceived barriers to access, with a specific focus on contraceptive services, and their consequences among Myanmar migrants in Japan.

STUDY DESIGN: From January to April 2020, we conducted 17 in-depth interviews with Myanmar migrant women and 4 key informant interviews with Myanmar interpreters working in health services in Tokyo, Saitama, and Chiba prefectures. We transcribed interviews and coded them in ATLAS.ti primarily using a deductive approach based on the 5 components of Levesque et al.'s conceptual framework of healthcare access. We also used inductive coding to allow for other themes outside of the framework to emerge.

RESULTS: Among the 17 women, almost half stated that they were using periodic abstinence based on the presumed fertility window or the withdrawal method. Furthermore, slightly over half of the women had a history of unintended pregnancy. Language barriers, limited health information sources, cultural and health beliefs and financial factors played important roles in access to contraceptives among Myanmar migrant women. Women described how these barriers resulted in feeling lack of control over family planning and unintended pregnancies.

CONCLUSIONS: Findings suggested that Myanmar migrants in Japan are faced with limited contraceptive access. Language barriers, limited information sources, health beliefs, and cultural and financial factors affected access.

IMPLICATIONS: Results suggest that to increase public awareness and contraceptive access of Myanmar women in Japan nonprofit support programs would benefit from the help of existing social networks of Myanmar migrants, interpreters, and Japanese doctors and researchers in reproductive health.}, } @article {pmid34045989, year = {2021}, author = {Miyajima, T and Murakami, F}, title = {Self-Interested Framed and Prosocially Framed Messaging Can Equally Promote COVID-19 Prevention Intention: A Replication and Extension of Jordan et al.'s Study (2020) in the Japanese Context.}, journal = {Frontiers in psychology}, volume = {12}, number = {}, pages = {605059}, pmid = {34045989}, issn = {1664-1078}, abstract = {How can we effectively promote the public's prevention of coronavirus disease 2019 (COVID-19) infection? Jordan et al. (2020) found with United States samples that emphasizing either self-interest or collective-interest of prevention behaviors could promote the public's prevention intention. Moreover, prosocially framed messaging was more effective in motivating prevention intention than self-interested messaging. A dual consideration of both cultural psychology and the literature on personalized matching suggests the findings of Jordan et al. (2020) are counterintuitive, because persuasion is most effective when the frame of the message delivered and the recipient of the message are culturally congruent. In order to better understand the potential influence of culture, the current research aimed to replicate and extend Jordan et al. (2020) findings in the Japanese context. Specifically, we examined the question (1) whether the relative effectiveness of the prosocial appeal is culturally universal and robust, (2) which types of 'others' especially promote prevention intention, and (3) which psychological mechanisms can explain the impact of messaging on prevention intention. In Study 1 (N = 1,583), we confirmed that self-interested framed, prosocially framed, and the combination of both types of messaging were equally effective in motivating prevention intention. In Study 2 (N = 1,686), we found that family-framed messaging also had a promoting effect similar to that from self-interested and prosocial appeals. However, the relative advantage of prosocial appeals was not observed. Further, a psychological propensity relevant to sensitivity to social rejection did not moderate the impact of messaging on prevention intention in both studies. These results suggest that since engaging in the infection control itself was regarded as critical by citizens after public awareness of COVID-19 prevention has been sufficiently heightened, for whom we should act might not have mattered. Further, concerns for social rejection might have had less impact on the prevention intentions under these circumstances. These results suggest that the relative advantage of a prosocial appeal might not be either culturally universal or prominent in a collectivistic culture. Instead, they suggest that the advantages of such an appeal depends on the more dynamic influence of COVID-19 infection.}, } @article {pmid34035906, year = {2020}, author = {Maaravi, Y and Heller, B}, title = {Studying the prominence effect amid the COVID-19 crisis: implications for public health policy decision-making.}, journal = {F1000Research}, volume = {9}, number = {}, pages = {1356}, pmid = {34035906}, issn = {2046-1402}, mesh = {Bias ; *COVID-19 ; Health Policy ; Humans ; SARS-CoV-2 ; }, abstract = {The novel coronavirus disease 2019 (COVID-19) has brought with it crucial policy- and decision-making situations, especially when making judgments between financial and health concerns. One particularly relevant decision-making phenomenon is the prominence effect, where decision-makers base their decisions on the most prominent attribute of the object at hand (e.g., health concerns) rather than weigh all the attributes together. This bias diminishes when the decision-making mode inhibits heuristic processes. In this study, we tested the prominence of health vs. financial concerns across two decision-making modes - choice (prone to heuristics) and matching (mitigates heuristics) - during the peak of the COVID-19 in the UK using Tversky et al.'s classic experimental paradigm. We added to the classic experimental design a priming condition. Participants were presented with two casualty-minimization programs, differing in lives saved and costs: program X would save 100 lives at the cost of 55-million-pound sterling, whereas program Y would save 30 lives at the cost of 12-million-pound sterling. Half of the participants were required to choose between the programs (choice condition). The other half were not given the cost of program X and were asked to determine what the cost should be to make it as equally attractive as the program Y. Participants in both groups were primed for either: a) financial concerns; b) health concerns; or c) control (no priming). Results showed that in the choice condition, unless primed for financial concerns, health concerns are more prominent. In the matching condition, on the other hand, the prominence of health concerns did not affect decision-makers, as they all "preferred" the cheaper option. These results add further support to the practical relevance of using the proper decision-making modes in times of consequential crises where multiple concerns, interests, and parties are involved.}, } @article {pmid34043069, year = {2021}, author = {Silva, ABJ and Silva, KG and Fernandes, MSS and Barros, WMA}, title = {Comment: Bardin et al.'s (2021) sex-related differences in accumulated O2-deficit incurre by high-intensity rowing exercise during childhood and adolescence. Eur J Appl Physiol.}, journal = {European journal of applied physiology}, volume = {121}, number = {8}, pages = {2365-2366}, pmid = {34043069}, issn = {1439-6327}, mesh = {Adolescent ; *Exercise ; Humans ; Oxygen Consumption ; *Water Sports ; }, } @article {pmid34030179, year = {2021}, author = {Crane, JM and Williamson, HJ and Raley, SK and Hagiwara, M and Lee, CE and Havercamp, SM}, title = {Who Is Leading the Field in 2020?: AAIDD Students and Early Career Professionals.}, journal = {Intellectual and developmental disabilities}, volume = {59}, number = {3}, pages = {217-223}, doi = {10.1352/1934-9556-59.3.217}, pmid = {34030179}, issn = {1934-9556}, mesh = {Humans ; *Intellectual Disability ; Students ; }, abstract = {The American Association on Intellectual and Developmental Disabilities (AAIDD) has been a leader in the field of intellectual and developmental disabilities since its founding in 1876. Today, student and early career professionals make up approximately 8.5% of the organization, with their engagement supported by the Student and Early Career Professional Interest Network (SECP). An article by Havercamp et al. (2003), "Who Will Lead the Field Beyond 2020?", recommended organizational changes that have been largely addressed in the years following by SECP. The present research replicates Havercamp et al.'s (2003) original survey of the organization's student and early career professionals, and results support the effectiveness of SECP as a welcoming platform from which students and early career professionals can establish themselves in the organization.}, } @article {pmid34025881, year = {2021}, author = {Gorgulu, R and Gokcek, E}, title = {The Effects of Avoiding Instructions Under Pressure: An Examination of the Volleyball Serving Task.}, journal = {Journal of human kinetics}, volume = {78}, number = {}, pages = {239-249}, pmid = {34025881}, issn = {1640-5544}, abstract = {Wegner predicts that under pressure self-avoiding instructions not to perform in a certain manner will break down precisely where it is least desired that is the hypothesis of the present study. Specifically, the aim was to test the hypothesis that when instructed not to serve into a certain zone, ironic error would be more prevalent under pressure. Our sample comprised 43 female participants between the age of 13 and 16 (Mage = 14.51, SD = 1.35) who were active volleyball players (Mtraining years = 5.40, SD = 2.38). We measured the participants' psychophysiological indications of anxiety via the heart rate, heart rate variability as well as the self-reported Mental Readiness Form-3. To measure performance, we counted the number of target and non-target serving zones under different anxiety conditions. Participants scored +5 points for serving into the target zone, scored -5 points for serving to the out or hitting the net and 1 point for serving into the court except the target zone. A 2 (anxiety) × 3 (serving zone) fully repeated measures ANOVA revealed a significant anxiety x serving zone interaction F (2, 84) = 36.52, p < .001. When instructed not to serve in a certain zone, players' overall performance did not change across anxiety conditions t (42) = .68, p =.50. Results did not provide support for the Wegner's theory as expected, but instead revealed evidence for the Woodman et al.'s (2015) differentiation of ironic performance error. The results demonstrate that the theory of ironic processes may account for practical instruction-based solution for reducing the susceptibility to ironic errors in the serving type of task in volleyball.}, } @article {pmid34023897, year = {2021}, author = {Lie, RT}, title = {Invited Commentary: Ionizing Radiation and Future Reproductive Health-Old Cohorts Still Deserve Attention.}, journal = {American journal of epidemiology}, volume = {190}, number = {11}, pages = {2334-2336}, doi = {10.1093/aje/kwab156}, pmid = {34023897}, issn = {1476-6256}, mesh = {Attention ; Female ; Humans ; *Neoplasms, Radiation-Induced ; *Nuclear Weapons ; Pregnancy ; Radiation, Ionizing ; Reproductive Health ; }, abstract = {Radiation from nuclear weapons or power plants has caused great concern among the public-concern that needs to be addressed with the best available data. Among the concerns associated with ionizing radiation are possible serious and far-reaching effects on reproductive health. Relevant data that can be used to address these concerns are scarce. The Hiroshima and Nagasaki bombings of World War II and the 1986 Chernobyl disaster in Ukraine are probably among the most dramatic and important sources of information on health effects, but much of the information is historical, and the exposed cohorts are getting old. In their accompanying article, Yamada et al. (Am J Epidemiol. 2021;190(11):2323-2333) revisit data on reproductive health outcomes in survivors of the Hiroshima and Nagasaki bombings during the years after the blasts. Exposure levels were very high, but after Yamada et al.'s reanalysis, effect estimates were low, and the evidence for overall effects on birth defects and perinatal mortality is still weak. The authors acknowledge that their data have limitations and that the generalizability of the findings is limited by the devastating conditions that prevailed in the 2 Japanese cities after the blasts.}, } @article {pmid33992026, year = {2021}, author = {Ezzina, S and Roume, C and Pla, S and Blain, H and Delignières, D}, title = {Restoring Walking Complexity in Older Adults Through Arm-in-Arm Walking: Were Almurad et al.'s (2018) Results an Artifact?.}, journal = {Motor control}, volume = {25}, number = {3}, pages = {475-490}, doi = {10.1123/mc.2020-0052}, pmid = {33992026}, issn = {1087-1640}, mesh = {Aged ; Arm ; *Gait ; Humans ; Motor Activity ; *Walking ; }, abstract = {The analysis of stride series revealed a loss of complexity in older people, which correlated with the falling propensity. A recent experiment evidenced an increase of walking complexity in older participants when they walked in close synchrony with a younger companion. Moreover, a prolonged experience of such synchronized walking yielded a persistent restoration of complexity. This result, however, was obtained with a unique healthy partner, and it could be related to a particular partner's behavior. The authors' aim was to replicate this important finding using a different healthy partner and to compare the results to those previously obtained. The authors successfully replicated the previous results: synchronization yielded an attraction of participants' complexity toward that of their partner and a restoration of complexity that persisted in two posttests, 2 and 6 weeks after the end of the training sessions. This study shows that this complexity restoration protocol can be applied successfully with another partner, and allows us to conclude that it can be generalized.}, } @article {pmid33982562, year = {2021}, author = {Asano, I and Sato, T}, title = {Partition of Block Copolymers in Phase-Separating Polymer Solutions.}, journal = {Langmuir : the ACS journal of surfaces and colloids}, volume = {37}, number = {20}, pages = {6268-6277}, doi = {10.1021/acs.langmuir.1c00704}, pmid = {33982562}, issn = {1520-5827}, abstract = {The distribution of the AB diblock copolymer in a phase-separating solution composed of immiscible A and B homopolymers in a common solvent has been investigated theoretically. We have utilized the mixing Gibbs energy density for the interfacial phase based on mean-field lattice theory to this four-component system. Distributions of the AB diblock copolymer in the A and B homopolymer-rich bulk phases and the interfacial region between the separating bulk phases are calculated as a function of the B-block content, degrees of polymerization of the copolymer and A and B homopolymers, as well as interaction parameters among the A and B monomer units and the solvent. The copolymer prefers to distribute more in the interfacial region rather than separating bulk phases at a higher copolymer degree of polymerization and a higher interaction parameter between A and B monomer units. The theory is also compared with Asano et al.'s experimental results [ Langmuir 2015, 31, 7488-7495] for polystyrene-b-poly(ethylene glycol) copolymer added to the phase-separating solution of polystyrene and poly(ethylene glycol) homopolymers dissolved in chloroform.}, } @article {pmid33975175, year = {2021}, author = {Malejka, S and Vadillo, MA and Dienes, Z and Shanks, DR}, title = {Correlation analysis to investigate unconscious mental processes: A critical appraisal and mini-tutorial.}, journal = {Cognition}, volume = {212}, number = {}, pages = {104667}, doi = {10.1016/j.cognition.2021.104667}, pmid = {33975175}, issn = {1873-7838}, mesh = {Bayes Theorem ; *Cognition ; Humans ; *Memory ; Research Design ; }, abstract = {As a method to investigate the scope of unconscious mental processes, researchers frequently obtain concurrent measures of task performance and stimulus awareness across participants. Even though both measures might be significantly greater than zero, the correlation between them might not, encouraging the inference that an unconscious process drives task performance. We highlight the pitfalls of this null-correlation approach and provide a mini-tutorial on ways to avoid them. As reference, we use a recent study by Salvador et al. (2018) reporting a non-significant correlation between the extent to which memory was suppressed by a Think/No-Think cue and an index of cue awareness. In the Null Hypothesis Significance Testing (NHST) framework, it is inappropriate to interpret failure to reject the null hypothesis (i.e., correlation = 0) as evidence for the null. Furthermore, psychological measures are often unreliable, which can dramatically attenuate the size of observed correlations. A Bayesian approach can circumvent both problems and compare the extent to which the data provide evidence for the null versus the alternative hypothesis (i.e., correlation > 0), while considering the usually low reliabilities of the variables. Applied to Salvador et al.'s data, this approach indicates no to moderate support for the claimed unconscious nature of participants' memory-suppression performance-depending on the model of the alternative hypothesis. Hence, more reliable data are needed. When analyzing correlational data, we recommend researchers to employ the Bayesian methods developed here (and made freely available as R scripts), rather than standard NHST methods, to take account of unreliability.}, } @article {pmid33972834, year = {2021}, author = {Motes-Rodrigo, A and Mundry, R and Call, J and Tennie, C}, title = {Evaluating the influence of action- and subject-specific factors on chimpanzee action copying.}, journal = {Royal Society open science}, volume = {8}, number = {2}, pages = {200228}, pmid = {33972834}, issn = {2054-5703}, abstract = {The ability to imitate has been deemed crucial for the emergence of human culture. Although non-human animals also possess culture, the acquisition mechanisms underlying behavioural variation between populations in other species is still under debate. It is especially controversial whether great apes can spontaneously imitate. Action- and subject-specific factors have been suggested to influence the likelihood of an action to be imitated. However, few studies have jointly tested these hypotheses. Just one study to date has reported spontaneous imitation in chimpanzees (Persson et al. 2017 Primates 59, 19-29), although important methodological limitations were not accounted for. Here, we present a study in which we (i) replicate the above-mentioned study addressing their limitations in an observational study of human-chimpanzee imitation; and (ii) aim to test the influence of action- and subject-specific factors on action copying in chimpanzees by providing human demonstrations of multiple actions to chimpanzees of varying rearing background. To properly address our second aim, we conducted a preparatory power analysis using simulated data. Contrary to Persson et al.'s study, we found extremely low rates of spontaneous chimpanzee imitation and we did not find enough cases of action matching to be able to apply our planned model with sufficient statistical power. We discuss possible factors explaining the lack of observed action matching in our experiments compared with previous studies.}, } @article {pmid33961926, year = {2021}, author = {Flowe, HD and Schreiber Compo, N}, title = {The lack of robust evidence for the effects of alcohol on false memory.}, journal = {Neuroscience and biobehavioral reviews}, volume = {127}, number = {}, pages = {332-333}, doi = {10.1016/j.neubiorev.2021.04.029}, pmid = {33961926}, issn = {1873-7528}, mesh = {*Ethanol ; Humans ; *Memory ; Prejudice ; }, abstract = {We comment on Kloft et al.'s (2021) review of the effects of alcohol and other drugs on false memory reporting. Across studies, problems of internal and external validity and methodological consistency preclude any blanket conclusions and recommendations regarding alcohol's effects on false memory reporting and suggestibility in witnesses. We argue that any policy and practice conclusions drawn from this limited literature are premature and would be unfairly prejudicial to witnesses and confusing to triers of fact at this time.}, } @article {pmid33956383, year = {2021}, author = {Gunaratne, R and Chong, YC and Heng, Y and Hahn, J and Lek, J and Randazzo, A and Brankov, B}, title = {Chronic Achilles tendon rupture: a novel modification of surgical technique described by El Shewy.}, journal = {ANZ journal of surgery}, volume = {91}, number = {7-8}, pages = {1447-1450}, doi = {10.1111/ans.16921}, pmid = {33956383}, issn = {1445-2197}, mesh = {*Achilles Tendon/surgery ; Humans ; Retrospective Studies ; Rupture/surgery ; *Tendon Injuries/surgery ; Treatment Outcome ; }, abstract = {BACKGROUND: Chronic Achilles tendon rupture is commonly defined as a rupture presenting 6 weeks after the time of injury and operative management is recommended. This research aims to describe a novel modified surgical technique in the repair of chronic Achilles tendon rupture and to report the result of this technique.

METHODS: This is a retrospective study performed between January 2007 and January 2017, and a novel modification of El Shewy et al.'s surgical technique is described. Fifteen patients with chronic rupture of Achilles tendon repaired with the technique by a single experienced surgeon were identified. Patients were contacted via phone call and questionnaires completed. Achilles Tendon Rupture Score and pain score were assessed via questionnaires.

RESULTS: Thirteen patients were contacted and two patients were uncontactable. Ten patients were able to return to their premorbid level of function. Twelve patients were satisfied or very satisfied with the outcome. Only one patient was very dissatisfied with the outcome. The average Achilles Tendon Rupture score was 72 (n = 7, 54%). The average pain score was 1.23 (n = 13, 100%).

CONCLUSIONS: This novel modified surgical technique demonstrated good functional outcomes and high levels of patient satisfaction in patient with chronic Achilles tendon rupture. It can be considered in the repair of chronic Achilles tendon rupture.}, } @article {pmid33952348, year = {2021}, author = {Stewart, T and Kilpela, L and Wesley, N and Baule, K and Becker, C}, title = {Psychometric properties of the contextual body image questionnaire for athletes: a replication and extension study in female collegiate athletes.}, journal = {Journal of eating disorders}, volume = {9}, number = {1}, pages = {59}, pmid = {33952348}, issn = {2050-2974}, support = {R01 MH094448/MH/NIMH NIH HHS/United States ; }, abstract = {BACKGROUND: Although the link between body dissatisfaction and eating disorder (ED) pathology is well-established in general female samples, less is known about contextual body image (CBI) among female athletes. CBI refers to female athletes' body image concerns in two contexts: sport and daily life. The Contextual Body Image Questionnaire for Athletes (CBIQA) measures four dimensions of body image (Appearance, Thin-Fat Self-Evaluation, Thin-Fat Others' Evaluation, and Muscularity) in both contexts. In a sample of female collegiate athletes, this study sought to A) investigate the psychometric properties of the CBIQA, B) examine the cross-sectional relation of CBI with ED pathology and negative affect, and C) assess the degree to which CBI prospectively predicts ED pathology and negative affect.

METHOD: Using self-report data collected from a multi-site parent trial, we examined the psychometric properties of the CBIQA by confirmatory factor analysis. We assessed construct and criterion validity via cross-sectional bivariate correlation analyses with thin-ideal internalization, negative affect, and ED pathology. Using data from Time 1 and 6 months later (Time 2), we investigated the degree to which CBI prospectively predicted ED pathology and negative affect.

RESULTS: Results from the CFA largely confirmed de Bruin et al.'s (2011) original factor analysis. Two CBIQA dimensions (Thin-Fat Self and Appearance) in both contexts correlated with ED pathology and negative affect. Thin-Fat Others also correlated with ED pathology in both contexts and negative affect in the sport context. The Muscularity dimension was predominantly orthogonal with other measures. CBIQA dimensions were uncorrelated with thin-ideal internalization. When controlling for BMI and Time 1 scores, daily life and sport appearance concerns predicted ED pathology, whereas perceived evaluation of thin-fat by others in the sport context predicted negative affect 6 months later.

CONCLUSIONS: Results support the psychometric validity of the CBIQA and suggest that it captures variance discrete from thin-ideal internalization. The Muscularity dimension largely was not related to other outcomes. Further, specific elements of perceived self- and other-evaluation in both contexts is relevant to risk for ED pathology and negative affect. Future research could examine the impact of dual body image between sports seasons and after transitioning out of sport.

CLINICAL TRIALS REGISTRATION: NCT01735994 .}, } @article {pmid33949924, year = {2022}, author = {LaVoi, NM and Glassford, SL}, title = {"This is Our Family": LGBTQ Family Narratives in Online NCAA D-I Coaching Biographies.}, journal = {Journal of homosexuality}, volume = {69}, number = {10}, pages = {1631-1654}, doi = {10.1080/00918369.2021.1921506}, pmid = {33949924}, issn = {1540-3602}, mesh = {Female ; Humans ; Male ; *Mentoring ; Narration ; *Sexual and Gender Minorities ; *Sports ; Universities ; }, abstract = {Intercollegiate sport in the US is known to be heteronormative, heterosexist, and often an unwelcoming space for LGBTQ individuals, including coaches. A decade ago, scholars documented the scarcity of LGBTQ family narratives in online coaching biographies on athletics Web sites. In the years following, a socio-cultural and legal shift occurred pertaining to LGBTQ rights and visibility in the US. This study extends and replicates Calhoun et al.'s research by examining family narratives of a sample of all NCAA Division-I head coaches of women's teams (N = 3601). Data collected in 2018 as part of the annual Women in College Coaching Report Card™ illustrated despite socio-cultural changes, very few (n = 18, .05%) online biographies included a same-sex family narratives-all were women. Eleven of the 18 head coaches were interviewed, and Erving Goffman's work was employed to theoretically ascertain why and how these women managed identities, stigma, enacted power, and performed character, namely courage. Implications and future research are offered.}, } @article {pmid33942719, year = {2021}, author = {Bifulco, SF and Scott, GD and Sarairah, S and Birjandian, Z and Roney, CH and Niederer, SA and Mahnkopf, C and Kuhnlein, P and Mitlacher, M and Tirschwell, D and Longstreth, WT and Akoum, N and Boyle, PM}, title = {Computational modeling identifies embolic stroke of undetermined source patients with potential arrhythmic substrate.}, journal = {eLife}, volume = {10}, number = {}, pages = {}, pmid = {33942719}, issn = {2050-084X}, support = {T32 EB001650/EB/NIBIB NIH HHS/United States ; MR/S015086/1/MRC_/Medical Research Council/United Kingdom ; 203148/Z/16/Z/WT_/Wellcome Trust/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; R01 HL152256/HL/NHLBI NIH HHS/United States ; RG/20/4/34803/BHF_/British Heart Foundation/United Kingdom ; U01 NS095869/NS/NINDS NIH HHS/United States ; }, mesh = {Aged ; Atrial Fibrillation/*complications/etiology ; Computer Simulation/*statistics & numerical data ; Embolic Stroke/*diagnosis/etiology ; Female ; Fibrosis/complications/diagnostic imaging ; Heart Atria/diagnostic imaging/pathology ; Humans ; Magnetic Resonance Imaging/standards/statistics & numerical data ; Male ; Middle Aged ; }, abstract = {Cardiac magnetic resonance imaging (MRI) has revealed fibrosis in embolic stroke of undetermined source (ESUS) patients comparable to levels seen in atrial fibrillation (AFib). We used computational modeling to understand the absence of arrhythmia in ESUS despite the presence of putatively pro-arrhythmic fibrosis. MRI-based atrial models were reconstructed for 45 ESUS and 45 AFib patients. The fibrotic substrate's arrhythmogenic capacity in each patient was assessed computationally. Reentrant drivers were induced in 24/45 (53%) ESUS and 22/45 (49%) AFib models. Inducible models had more fibrosis (16.7 ± 5.45%) than non-inducible models (11.07 ± 3.61%; p<0.0001); however, inducible subsets of ESUS and AFib models had similar fibrosis levels (p=0.90), meaning that the intrinsic pro-arrhythmic substrate properties of fibrosis in ESUS and AFib are indistinguishable. This suggests that some ESUS patients have latent pre-clinical fibrotic substrate that could be a future source of arrhythmogenicity. Thus, our work prompts the hypothesis that ESUS patients with fibrotic atria are spared from AFib due to an absence of arrhythmia triggers.}, } @article {pmid33936304, year = {2020}, author = {Canaz, G and Canaz, H and Erdogan, ET and Alatas, I and Emel, E and Matur, Z}, title = {Evaluation of Neurological Examination, SEP Results, MRI Results, and Lesion Levels in Patients Who Had Been Operated for Myelomeningocele.}, journal = {Journal of pediatric neurosciences}, volume = {15}, number = {4}, pages = {393-401}, pmid = {33936304}, issn = {1817-1745}, abstract = {OBJECTIVE: Myelomeningocele is the most severe and the most frequent form of spina bifida. Most of the myelomeningocele patients undergo operations in new-born age. In terms of life quality and rehabilitation, follow-up's of these patients in the growth and development period after the operation is critical. In our study, our aim is to emphasize the correlation of SEP results with MRI results and clinical features of the myelomeningocele patients.

MATERIALS AND METHODS: In our study, we included 36 patients who had undergone myelomeningocele operation and have been followed-up in Istanbul Bilim University Florence Nightingale Hospital, Spina Bifida Research and Treatment Centre. Posterior tibial nerve SEP was performed on each patient and neurological examinations were done in the same session. Results were compared with clinical functional lesion levels, levels of fusion defect and ambulation levels. In order to evaluate SEP results, we used age-related reference values from Boor et al.'s study in 2008. Patients were grouped as normal, unilaterally prolonged, bilaterally prolonged, unilaterally lost, and bilaterally lost.

RESULTS: The correlations of posterior tibial nerve SEP results were significant with ambulation levels (r = 0.428, P < 0.01), clinical functional lesion levels (r = 0.477, P < 0.01) and fusion defect levels (r = -0.528 P < 0.05). The lumbar SEP results were only significantly correlated with functional lesion levels (r = 0.443 P < 0.05).

CONCLUSIONS: Radiological studies are insufficient when evaluating the functionality of the central nervous system. To fully evaluate the functionality and watch the neurological development with accuracy, especially in operated patients, electrophysiological studies should be an indispensable part of myelomeningocele follow-ups.}, } @article {pmid33927667, year = {2021}, author = {Hao, J and Du, X}, title = {Preschoolers' Helping Motivations: Altruistic, Egoistic or Diverse?.}, journal = {Frontiers in psychology}, volume = {12}, number = {}, pages = {614868}, pmid = {33927667}, issn = {1664-1078}, abstract = {Based on Eisenberg et al.'s model of prosocial motivations, the present study examined what motivates preschoolers to display instrumental helping and how various motivations develop during the preschool years. The participants were 477 preschoolers aged 3-5 years assigned to one of five groups. In each experimental group, the experimenter emphasized an altruistic or egoistic helping motivation, namely, empathic concern, moral rules, praise or rewards. In the control group, no helping motivations were emphasized. Their instrumental helping was then measured by sorting cards for a sick child to play a game. The results show that each helping motivation had a positive effect on instrumental helping. Most of the motivational effects were similar across age, but the motivational effect of empathic concern increased obviously at the age of 5 years. Therefore, the present study reveals that both altruistic and egoistic motivations motivate preschoolers to help others. Most of the motivations develop steadily during the preschool years, but empathic concern as an altruistic motivation increases greatly at the end of the preschool years. The present study thus confirms the diversity of preschoolers' helping motivations with Eisenberg et al.'s model of prosocial motivations.}, } @article {pmid33916536, year = {2021}, author = {Matos, R and Monteiro, D and Antunes, R and Mendes, D and Botas, J and Clemente, J and Amaro, N}, title = {Home-Advantage during COVID-19: An Analysis in Portuguese Football League.}, journal = {International journal of environmental research and public health}, volume = {18}, number = {7}, pages = {}, pmid = {33916536}, issn = {1660-4601}, support = {UIDB/04748/2020//Fundação para a Ciência e a Tecnologia/ ; }, mesh = {*COVID-19 ; *Football ; Humans ; Pandemics ; Portugal ; SARS-CoV-2 ; }, abstract = {Covid-19 pandemic forced, at the final rounds of 2019-2020 season, in many different sport leagues worldwide, teams to play without an audience. Therefore, the present paper aims to compare the home advantage score in the last ten rounds in 2019-2020 season with the first 24 rounds in same season using Pollard's (1986) and Matos et al.'s (2020) methods. In addition, comparisons across different seasons (2016-2017; 2017-2018; 2018-2019 and 2019-2020) using the same methods were also analyzed. Results showed no differences (p > 0.05) between first 24 rounds and the last 10 in 2019-2020 season as well as in the 3 previous seasons. With Pollard's method, no differences (p > 0.05) were also found among those four seasons on global (all 34 rounds) home advantage. However, a significance difference between 2017-2018 and 2019-2020 (p < 0.05) was founded using Matos et al.'s (2020) method, which is an indicator of the importance of using complementary methods when analyzing the same realities. Overall, despite what might be expectable from recent findings, the lack of an audience in the last 10 rounds of Portuguese Football League 2019-2020 season, due to COVID-19 pandemic, did not affect home advantage. Therefore, future studies could try to analyze other different variables in Portuguese Football League, such as referees' behaviors, rules changing (e.g., the possibility of making five substitutions, instead of three), crowd dimension and density as well as include variables about odds as forecasts in football being played without crowds.}, } @article {pmid33915556, year = {2021}, author = {Brockett-Walker, C and Lall, M and Evans, DD and Heron, S}, title = {Racial Bias Among Emergency Providers: Strategies to Mitigate Its Adverse Effects.}, journal = {Advanced emergency nursing journal}, volume = {43}, number = {2}, pages = {89-101}, doi = {10.1097/TME.0000000000000352}, pmid = {33915556}, issn = {1931-4493}, mesh = {Adult ; Awareness ; *Emergency Service, Hospital ; Female ; Humans ; Nurse Practitioners/*psychology ; Personnel, Hospital/*psychology ; Pregnancy ; Prejudice ; Racism/*psychology ; }, abstract = {The Research to Practice column presents an analysis of current and controversial research findings with implications for practice change relevant to emergency care settings. This review critiques Johnson et al.'s (2016) investigation, titled "The Impact of Cognitive Stressors in the Emergency Department on Physician Implicit Racial Bias," that examined emergency department characteristics and stressors and their effects on physician racial bias and decision making. Their findings suggest that unconscious biases can affect clinical decisions when providers experience increased cognitive stress. The implications are significant for emergency providers as resources are especially strained during the COVID-19 pandemic and as the adverse effects of unconscious bias on health disparities and patient outcomes have become clearly apparent. Implicit bias training (IBT) is recommended for emergency providers and has significant implications for medical and nurse educators in executing and evaluating IBT outcomes.}, } @article {pmid33910410, year = {2022}, author = {Wesselmann, ED and Boyd, SW and Arellanes, JA and Driskell, A and Hesson-McInnis, MS}, title = {Manipulating Environmental Commitment: A Replication and Extension.}, journal = {Psychological reports}, volume = {125}, number = {4}, pages = {2178-2190}, doi = {10.1177/00332941211012621}, pmid = {33910410}, issn = {1558-691X}, mesh = {Humans ; *Personal Satisfaction ; }, abstract = {Environmental commitment, the subjective experience of dependence on the natural environment, is marked by a long-term orientation and psychological attachment towards the natural environment. The current research replicates and extends previous research on temporarily increasing environmental commitment (Davis et al., 2009). We employed Davis et al.'s manipulation in two experimental studies (one laboratory, one online): we asked participants to spend time writing either about ways in which they are interdependent with the natural environment (high commitment manipulation) or unconnected with the environment (low commitment manipulation). In both studies we replicated the key finding that reflecting on one's interdependence with the environment increases commitment. We extended the previous research by finding evidence that this commitment effect was mediated by satisfaction with one's relationship to the environment. We did not replicate the original findings that the interdependence manipulation influences environmental behavioral intentions.}, } @article {pmid33903404, year = {2021}, author = {Schodde, R and Christidis, L and Batalha-Filho, H and Ericson, PGP and Irestedt, M}, title = {Why neotypification of emLophorina/em emsuperba/em (Pennant, 1781) (Aves: Paradisaeidae) is justified-and necessary.}, journal = {Zootaxa}, volume = {4951}, number = {2}, pages = {zootaxa.4951.2.5}, doi = {10.11646/zootaxa.4951.2.5}, pmid = {33903404}, issn = {1175-5334}, mesh = {Animals ; Male ; *Passeriformes/classification ; }, abstract = {We review Irestedt et al.'s (2017) neotypification of the senior species name superba Pennant, 1781 in the bird-of-paradise genus Lophorina in response to Elliott et al. (2020) who challenged the resultant shift in name from the small isolate in New Guinea's Vogelkop to the widespread species in the island's central cordillera. In nine male plumage traits which differentiate the two species, six of which had been identified as novel by Irestedt et al., we show that the only two figures of the perished male holotype of superba match the central cordillera species more closely than the Vogelkop. We find as well that not only was the trading of bird-of-paradise skins from the central cordillera to coastal ports in the Vogelkop feasible before European contact, but application of superba to the central cordillera species also promotes nomenclatural stability: the name has been used overwhelmingly at species rank for that widespread form throughout post-19th century media. Re-assessment of Irestedt et al.'s point-by-point justification of neotypification under Article 75.3 of the ICZN (1999) Code establishes, furthermore, that their case meets the requirements of every condition specified in the article; the neotypification is thus valid. Elliott et al.'s alternative to fix superba to the Vogelkop isolate by type locality restriction is not Code-compliant, nor is their evidence for interpreting J.R. Forster as the author of the name. In conclusion, we lay out the correct nomenclature for the taxa of Lophorina under the Code.}, } @article {pmid33894422, year = {2021}, author = {Cornelissen, PL and Brokjøb, LG and Gumančík, J and Cornelissen, KK}, title = {Women's self-estimates of body size are more accurate and precise when made with three-quarter view than front-view stimuli.}, journal = {Body image}, volume = {38}, number = {}, pages = {171-180}, doi = {10.1016/j.bodyim.2021.04.003}, pmid = {33894422}, issn = {1873-6807}, mesh = {Adult ; *Body Image/psychology ; *Body Size ; Female ; Humans ; Reproducibility of Results ; *Visual Perception ; }, abstract = {Recently, Cornelissen, Cornelissen, Groves, McCarty and Tovée (2018) asked which image orientations (e.g. front-, side-, or three-quarter view) are most appropriate for tasks which are used for self-estimates of body size and shape. Based on psychophysical measurements, they showed that front view stimuli showed substantially poorer content validity compared to side- and three-quarter view stimuli. Here, we tested the real-world consequences of Cornelissen et al.'s (2018) findings. We carried out a body size self-estimation task in a sample of healthy adult women, once with front view stimuli, and once with three-quarter view stimuli. The order in which front- and three-quarter view tasks were carried out was randomized across participants. Compared to three-quarter view stimuli, we found that: a) the precision of participants' judgements was worse with front view stimuli, and b) that front view stimuli led to over-estimation of body size by ∼1.7 BMI units. While these results need to be replicated, they do suggest that careful consideration needs to be given to stimulus orientation in future studies.}, } @article {pmid33882919, year = {2021}, author = {Staal, J and Alsma, J and Mamede, S and Olson, APJ and Prins-van Gilst, G and Geerlings, SE and Plesac, M and Sundberg, MA and Frens, MA and Schmidt, HG and Van den Broek, WW and Zwaan, L}, title = {The relationship between time to diagnose and diagnostic accuracy among internal medicine residents: a randomized experiment.}, journal = {BMC medical education}, volume = {21}, number = {1}, pages = {227}, pmid = {33882919}, issn = {1472-6920}, mesh = {Bias ; Diagnostic Errors ; Humans ; *Internal Medicine ; *Problem Solving ; }, abstract = {BACKGROUND: Diagnostic errors have been attributed to cognitive biases (reasoning shortcuts), which are thought to result from fast reasoning. Suggested solutions include slowing down the reasoning process. However, slower reasoning is not necessarily more accurate than faster reasoning. In this study, we studied the relationship between time to diagnose and diagnostic accuracy.

METHODS: We conducted a multi-center within-subjects experiment where we prospectively induced availability bias (using Mamede et al.'s methodology) in 117 internal medicine residents. Subsequently, residents diagnosed cases that resembled those bias cases but had another correct diagnosis. We determined whether residents were correct, incorrect due to bias (i.e. they provided the diagnosis induced by availability bias) or due to other causes (i.e. they provided another incorrect diagnosis) and compared time to diagnose.

RESULTS: We did not successfully induce bias: no significant effect of availability bias was found. Therefore, we compared correct diagnoses to all incorrect diagnoses. Residents reached correct diagnoses faster than incorrect diagnoses (115 s vs. 129 s, p < .001). Exploratory analyses of cases where bias was induced showed a trend of time to diagnose for bias diagnoses to be more similar to correct diagnoses (115 s vs 115 s, p = .971) than to other errors (115 s vs 136 s, p = .082).

CONCLUSIONS: We showed that correct diagnoses were made faster than incorrect diagnoses, even within subjects. Errors due to availability bias may be different: exploratory analyses suggest a trend that biased cases were diagnosed faster than incorrect diagnoses. The hypothesis that fast reasoning leads to diagnostic errors should be revisited, but more research into the characteristics of cognitive biases is important because they may be different from other causes of diagnostic errors.}, } @article {pmid33880104, year = {2020}, author = {Delgado-Sánchez, A}, title = {Does It Feel Right or Wrong? The Neuroscience of Moral Judgement.}, journal = {Journal of undergraduate neuroscience education : JUNE : a publication of FUN, Faculty for Undergraduate Neuroscience}, volume = {19}, number = {1}, pages = {R4-R6}, pmid = {33880104}, issn = {1544-2896}, abstract = {Moral judgement has been a topic of great interest through the history of philosophy and psychology, but the neural basis of this behavior remains elusive. Greene et al.'s (2001) paper is a pioneering one that opened doors to studying the neuroscience of moral judgement. Greene and colleagues used functional Magnetic Resonance Imaging (fMRI) to measure brain activity in humans as they grappled with moral decisions. The researchers found higher activation in brain areas associated with emotion when subjects were processing dilemmas in which an individual was directly hurt, and higher activation of areas associated with working memory when subjects processed dilemmas in which individuals were hurt as a consequence of an indirect action. The paper has received some criticism, but overall, is still quite relevant in the field. This work generated the field of moral neuroscience and has sparked further research and controversy. This paper's impact at the intersection of psychology and neuroscience and its engaging topic make it valuable for teaching. Furthermore, criticism of the paper also has pedagogic value as it can serve as a tool to promote students' critical evaluation skills. The presentation of this research would be best suited for Neuroscience and Psychology students being introduced to Cognitive Neuroscience.}, } @article {pmid33871272, year = {2021}, author = {Van Iddekinge, CH and Aguinis, H and LeBreton, JM and Mackey, JD and DeOrtentiis, PS}, title = {Assessing and interpreting interaction effects: A reply to Vancouver, Carlson, Dhanani, and Colton (2021).}, journal = {The Journal of applied psychology}, volume = {106}, number = {3}, pages = {476-488}, doi = {10.1037/apl0000883}, pmid = {33871272}, issn = {1939-1854}, mesh = {Humans ; *Motivation ; *Research Design ; }, abstract = {Van Iddekinge et al. (2018)'s meta-analysis revealed that ability and motivation have mostly an additive rather than an interactive effect on performance. One of the methods they used to assess the ability × motivation interaction was moderated multiple regression (MMR). Vancouver et al. (2021) presented conceptual arguments that ability and motivation should interact to predict performance, as well as analytical and empirical arguments against the use of MMR to assess interaction effects. We describe problems with these arguments and show conceptually and empirically that MMR (and the ΔR and ΔR2 it yields) is an appropriate and effective method for assessing both the statistical significance and magnitude of interaction effects. Nevertheless, we also applied the alternative approach Vancouver et al. recommended to test for interactions to primary data sets (k = 69) from Van Iddekinge et al. These new results showed that the ability × motivation interaction was not significant in 90% of the analyses, which corroborated Van Iddekinge et al.'s original conclusion that the interaction rarely increments the prediction of performance beyond the additive effects of ability and motivation. In short, Van Iddekinge et al.'s conclusions remain unchanged and, given the conceptual and empirical problems we identified, we cannot endorse Vancouver et al.'s recommendation to change how researchers test interactions. We conclude by offering suggestions for how to assess and interpret interactions in future research. (PsycInfo Database Record (c) 2021 APA, all rights reserved).}, } @article {pmid33867369, year = {2021}, author = {Shanmugam, R}, title = {The lengths of spinal curvature stretch due to the angles of sitting on saddle chair to alleviate back pain: A statistical analysis.}, journal = {Work (Reading, Mass.)}, volume = {68}, number = {4}, pages = {1027-1033}, doi = {10.3233/WOR-213433}, pmid = {33867369}, issn = {1875-9270}, mesh = {Back Pain ; Humans ; Interior Design and Furnishings ; *Low Back Pain ; Posture ; *Spinal Curvatures ; }, abstract = {BACKGROUND: By dividing the burden of one's weight between the shins and the buttocks in the sitting position on an office or saddle chair, a person can avoid back pain. In this 21st century, sitting on a chair for long hours in workplace on office chair is unavoidable necessity and hence, millions in different countries undergo a risk for backpain. Is there a right sitting position?

OBJECTIVE: The aim of this article is to find out how much a correlation exists between the angle of sitting and the length of spinal curvature which is the source of backpain. An experiment can be designed and carried out to measure various angles in sitting and the changing length of the person's spinal cord curvature.

METHOD: The usual statistical methodology requires a pair of values namely x and y to quantify the correlation. The data on sitting angles and the length of spinal curvature do not have such pairing, and hence, the traditional approach to find the correlation between the sitting angle and length of spinal curvature is not applicable. Yet, an approach is necessary. This article constructs an innovative statistical approach to fulfil this need.

RESULTS: Our approach yields a correlation of 0.998 for sitting on office chair and an increased correlation of 0.999 on saddle chair, according to the Truszczyńska-Baszaka et al.'s data.

CONCLUSIONS: An adjustment is made in various angles of sitting on office chair to transform the comfortable sitting on a saddle chair. In consequence, the proportional effect on the spinal curvature is estimable with the data and it is phenomenal (that is significantly more than one). No wonder people prefer saddle chair over office chair when it comes to avoid back pain and this article proves the convenience statistically.}, } @article {pmid33861342, year = {2021}, author = {Mullie, P and Maes, P and van Veelen, L and Van Tiggelen, D and Clarys, P}, title = {Energy Balance and Energy Availability During a Selection Course for Belgian Paratroopers.}, journal = {Military medicine}, volume = {186}, number = {11-12}, pages = {1176-1182}, doi = {10.1093/milmed/usab140}, pmid = {33861342}, issn = {1930-613X}, mesh = {Adult ; Belgium ; Eating ; *Energy Intake ; *Energy Metabolism ; Exercise ; Humans ; }, abstract = {INTRODUCTION: Adequate energy supply is a prerequisite for optimal performances and recovery. The aims of the present study were to estimate energy balance and energy availability during a selection course for Belgian paratroopers.

METHODS: Energy expenditure by physical activity was measured with accelerometer (ActiGraph GT3X+, ActiGraph LLC, Pensacola, FL, USA) and rest metabolic rate in Cal.d-1 with Tinsley et al.'s equation based on fat-free mass = 25.9 × fat-free mass in kg + 284. Participants had only access to the French individual combat rations of 3,600 Cal.d-1, and body fat mass was measured with quadripolar impedance (Omron BF508, Omron, Osaka, Japan). Energy availability was calculated by the formula: ([energy intake in foods and beverages] - [energy expenditure physical activity])/kg FFM-1.d-1, with FFM = fat-free mass.

RESULTS: Mean (SD) age of the 35 participants was 25.1 (4.18) years, and mean (SD) percentage fat mass was 12.0% (3.82). Mean (SD) total energy expenditure, i.e., the sum of rest metabolic rate, dietary-induced thermogenesis, and physical activity, was 5,262 Cal.d-1 (621.2), with percentile 25 at 4,791 Cal.d-1 and percentile 75 at 5,647 Cal.d-1, a difference of 856 Cal.d-1. Mean daily energy intake was 3,600 Cal.d-1, giving a negative energy balance of 1,662 (621.2) Cal.d-1. Mean energy availability was 9.3 Cal.kg FFM-1.d-1. Eleven of the 35 participants performed with a negative energy balance of 2,000 Cal.d-1, and only five participants out of 35 participants performed at a less than 1,000 Cal.d-1 negative energy balance level.

CONCLUSIONS: Energy intake is not optimal as indicated by the negative energy balance and the low energy availability, which means that the participants to this selection course had to perform in suboptimal conditions.}, } @article {pmid33858035, year = {2021}, author = {Zhang, SY and Demant, J}, title = {Effects of self-control, drug-use peers and family attachment on drug use among Chinese users: A gender-specific analysis.}, journal = {Drug and alcohol review}, volume = {40}, number = {7}, pages = {1369-1376}, doi = {10.1111/dar.13295}, pmid = {33858035}, issn = {1465-3362}, mesh = {China/epidemiology ; Cross-Sectional Studies ; *Drug and Narcotic Control ; Female ; Humans ; Male ; Peer Group ; *Self-Control ; }, abstract = {INTRODUCTION: The increasing trend of synthetic drug use has been a significant concern in China. The current research adopted a gendered perspective to examine the effects of self-control, drug-use peers and family attachment on drug use frequency in China.

METHODS: This cross-sectional survey research recruited 785 people who used drugs from four compulsory drug rehabilitation institutions in Guangdong and Shandong Province of China in 2018. Ordinary least squares regression analyses were conducted to examine the gendered effects of self-control (Grasmick et al.'s cognitive scale), drug-use peers and family attachment on drug use frequency.

RESULTS: Low self-control was neither a significant nor gendered predictor of drug use frequency when controlling for effects of drug-use peers and family attachment. Drug-use peers strongly increased participants' drug use frequency, regardless of gender. However, an important finding is that for males, support from families reduced drug use frequency but conversely meeting and contact with families increased drug use frequency. For females, only trust in families prevented their further involvement in drug use.

DISCUSSION AND CONCLUSIONS: Low self-control may not be a core explanatory factor for drug use behaviours in China. Thus, treatment programs should focus more on skills building than self-control. Future programs could focus more on reducing association with their drug-use peers and further explore the complex relationships with their families. Gender should be considered in treatment options.}, } @article {pmid33852562, year = {2021}, author = {Yeates, EO and Nahmias, J}, title = {Response to Wyatt et al.'s comment on "Changes in traumatic mechanisms of injury in Southern California related to COVID-19: Penetrating trauma as a second pandemic".}, journal = {The journal of trauma and acute care surgery}, volume = {91}, number = {1}, pages = {e38}, pmid = {33852562}, issn = {2163-0763}, mesh = {*COVID-19 ; California/epidemiology ; Humans ; Pandemics ; SARS-CoV-2 ; *Wounds, Penetrating/epidemiology ; }, } @article {pmid33843563, year = {2022}, author = {Caron-Roy, S and Sayed, SA and Milaney, K and Lashewicz, B and Dunn, S and O'Hara, H and Leblanc, P and Fournier, B and Raine, KD and Elliott, C and Prowse, RJ and Olstad, DL}, title = {'My coupons are like gold': experiences and perceived outcomes of low-income adults participating in the British Columbia Farmers' Market Nutrition Coupon Program.}, journal = {Public health nutrition}, volume = {25}, number = {2}, pages = {410-421}, pmid = {33843563}, issn = {1475-2727}, support = {FRN 155916//CIHR/Canada ; }, mesh = {Adult ; British Columbia ; *Farmers ; *Food Assistance ; Food Supply ; Fruit ; Humans ; Poverty ; Vegetables ; }, abstract = {OBJECTIVE: The British Columbia Farmers' Market Nutrition Coupon Program (FMNCP) provides low-income households with coupons valued at $21/week for 16 weeks to purchase healthy foods in farmers' markets. Our objective was to explore FMNCP participants' experiences of accessing nutritious foods, and perceived programme outcomes.

DESIGN: The current study used qualitative description methodology. Semi-structured interviews were conducted with FMNCP participants during the 2019 farmers' market season. Directed content analysis was used to analyse the data, whereby the five domains of Freedman et al.'s framework of nutritious food access provided the basis for an initial coding scheme. Data that did not fit within the framework's domains were coded inductively.

SETTING: One urban and two rural communities in British Columbia, Canada.

PARTICIPANTS: Twenty-eight adults who were participating in the FMNCP.

RESULTS: Three themes emerged: autonomy and dignity, social connections and community building, and environmental and programmatic constraints. Firstly, the programme promoted a sense of autonomy and dignity through financial support, increased access to high-quality produce, food-related education and skill development and mitigating stigma and shame. Secondly, shopping in farmers' markets increased social connections and fostered a sense of community. Finally, participants experienced limited food variety in rural farmers' markets, lack of transportation and challenges with redeeming coupons.

CONCLUSIONS: Participation in the FMNCP facilitated access to nutritious foods and enhanced participants' diet quality, well-being and health. Strategies such as increasing the amount and duration of subsidies and expanding programmes may help improve participants' experiences and outcomes of farmers' market food subsidy programmes.}, } @article {pmid33842892, year = {2021}, author = {Lu, K and Yao, R and Xu, W and Ning, H and Zhang, X and Zhang, G and Li, Y and Zhong, J and Yang, Y and Peng, J}, title = {Alloy-Electrode-Assisted High-Performance Enhancement-Type Neodymium-Doped Indium-Zinc-Oxide Thin-Film Transistors on Polyimide Flexible Substrate.}, journal = {Research (Washington, D.C.)}, volume = {2021}, number = {}, pages = {5758435}, pmid = {33842892}, issn = {2639-5274}, abstract = {Flexible thin-film transistors with high current-driven capability are of great significance for the next-generation new display technology. The effect of a Cu-Cr-Zr (CCZ) copper alloy source/drain (S/D) electrode on flexible amorphous neodymium-doped indium-zinc-oxide thin-film transistors (NdIZO-TFTs) was investigated. Compared with pure copper (Cu) and aluminum (Al) S/D electrodes, the CCZ S/D electrode changes the TFT working mode from depletion mode to enhancement mode, which is ascribed to the alloy-assisted interface layer besides work function matching. X-ray photoelectron spectroscopy (XPS) depth profile analysis was conducted to examine the chemical states of the contact interface, and the result suggested that chromium (Cr) oxide and zirconium (Zr) oxide aggregate at the interface between the S/D electrode and the active layer, acting as a potential barrier against residual free electron carriers. The optimal NdIZO-TFT exhibited a desired performance with a saturation mobility (μ sat) of 40.3 cm[2]·V[-1]·s[-1], an I on/I off ratio of 1.24 × 10[8], a subthreshold swing (SS) value of 0.12 V·decade[-1], and a threshold voltage (V th) of 0.83 V. This work is anticipated to provide a novel approach to the realization of high-performance flexible NdIZO-TFTs working in enhancement mode.}, } @article {pmid33842802, year = {2021}, author = {Gisondi, MA and Branzetti, J and Hopson, LR and Regan, L}, title = {Sustainable Engaged Accountable Learners.}, journal = {AEM education and training}, volume = {5}, number = {2}, pages = {e10470}, pmid = {33842802}, issn = {2472-5390}, abstract = {The development of lifelong learners is among the most challenging goals for medical educators. The authors identify two important scholarly works that profoundly altered their understanding and approach to lifelong learning and curriculum design: L. Dee Fink's Taxonomy of Significant Learning and Cutrer et al.'s Master Adaptive Learner model. By applying these guides to their teaching and related research, three important characteristics of lifelong learning became evident: sustainability, engagement, and accountability. These are abbreviated "SEALs," for sustainable engaged accountable learners. This paper defines these qualities as they relate to emergency medicine training, significant learning, and the development of adaptive expertise. Connections to Fink's and Cutrer's works are offered for each learner characteristic. Educational and psychological theories that support the SEALs model are paired with practical suggestions for educators to promote these desired qualities in their trainees. Relevant features of adult learning are highlighted, including self-regulation, motivation, agency, and autonomy.}, } @article {pmid33840902, year = {2021}, author = {Rietveld, G and van Wijk, J and Bolhuis, MP}, title = {Who wants 'the worst of the worst'? Rationales for and consequences of third country resettlement of Guantanamo Bay detainees.}, journal = {Crime, law, and social change}, volume = {76}, number = {1}, pages = {35-83}, pmid = {33840902}, issn = {0925-4994}, abstract = {Against the backdrop of countries increasingly being confronted with undesirable but unreturnable non-citizen terrorist suspects, this article describes the resettlement process of 150 cleared but unreturnable Guantanamo Bay detainees. Merely 13% of these detainees have been resettled in full democracies, compared to 52% in authoritarian regimes. Using Starkley et al.'s concept of 'zone agreement' the article explains how the U.S. particularly managed to incentivize pragmatically oriented - rather than idealistically motivated - governments to engage in third country resettlement [16]. From the perspective of the U.S. the resettlement scheme can be considered relatively successful, while the experiences of resettlement countries and the resettled detainees themselves have been very mixed.}, } @article {pmid33832287, year = {2021}, author = {Chen, P and Lin, X and Chen, B and Zheng, K and Lin, C and Yu, B and Lin, F}, title = {The global state of research and trends in osteomyelitis from 2010 to 2019: a 10-year bibliometric analysis.}, journal = {Annals of palliative medicine}, volume = {10}, number = {4}, pages = {3726-3738}, doi = {10.21037/apm-20-1978}, pmid = {33832287}, issn = {2224-5839}, mesh = {*Bibliometrics ; China ; England ; France ; Germany ; Humans ; *Osteomyelitis ; United States ; }, abstract = {BACKGROUND: Osteomyelitis is a difficult problem for orthopedic surgeons due to its great harm and complicated treatment. In this study, we aim to make a bibliometric analysis of the literature related to osteomyelitis and explore the research status, hotspots and frontiers in this field in recent 10 years.

METHODS: Literature relating to osteomyelitis from 2010 to 2019 was retrieved from the database of Science Citation Index Expanded (SCIE) of Web of Science. CiteSpace was used to analyze country/institution, authors/cited authors, cited journals, cited references, and keywords. An analysis of counts and centrality was used to reveal publication outputs, countries/institutions, core journals, active authors, hot topics, and frontiers.

RESULTS: A total of 6,421 valid literatures were retrieved. The most productive country and institution were the United States and Shanghai Jiao Tong University, respectively. Researchers and institutions from the United States, Germany, England, and France were the core research forces. There was a broad and close cooperation worldwide. Lipsky BA [24] was the most productive first author, and Lew DP [487] was the most frequently cited author. Lipsky et al.'s [2012] article (co-citation counts, 146) was the most representative and symbolic reference. Journal of Foot Ankle Surgery [111] was the most productive journal. Clin Infect Dis [2,275] was the most frequently co-cited journal. Staphylococcus aureus infection and the diagnosis, treatment and management strategy of osteomyelitis were the hot spots. Epidemiology, diabetic foot, treatment, especially antibiotics, biofilm and in vitro research were research frontiers.

CONCLUSIONS: This study reveals the current research status and hot spots in the field of osteomyelitis in recent 10 years, which may help researchers to identify further potential perspectives on collaborators, research frontiers, and hot topics.}, } @article {pmid33826434, year = {2022}, author = {Arnold, T and Stopka, TJ and Gomillia, CES and Murphy, M and Johnson, K and Chan, PA and Klasko-Foster, L and Rogers, B and Soler, JH and Monger, ML and Jacque, E and Sutten Coats, C and Willie, TC and Ogunbajo, A and Mena, L and Nunn, A}, title = {Locating the Risk: Using Participatory Mapping to Contextualize Perceived HIV Risk across Geography and Social Networks among Men Who Have Sex with Men in the Deep South.}, journal = {Journal of sex research}, volume = {59}, number = {7}, pages = {931-938}, pmid = {33826434}, issn = {1559-8519}, support = {T32 MH078788/MH/NIMH NIH HHS/United States ; R25 MH083620/MH/NIMH NIH HHS/United States ; U01 AI069470/AI/NIAID NIH HHS/United States ; UM1 AI069470/AI/NIAID NIH HHS/United States ; K01 MH129165/MH/NIMH NIH HHS/United States ; P30 AI042853/AI/NIAID NIH HHS/United States ; R34 MH109371/MH/NIMH NIH HHS/United States ; }, mesh = {Geography ; *HIV Infections/epidemiology/prevention & control ; Homosexuality, Male ; Humans ; Male ; Risk-Taking ; Sexual Behavior ; *Sexual and Gender Minorities ; Social Networking ; }, abstract = {HIV incidence among African American (AA) young men who have sex with men (YMSM) has remained stable even though they made up the largest number of new HIV diagnoses among men who have sex with men (MSM) in 2017. HIV spreads at increased rates in dense sexual networks. Identifying the location of risk behaviors "activity spaces" could inform geographically circumscribed HIV prevention interventions. Utilizing the modified social ecological model we completed five semi-structured focus groups incorporating a modified social mapping technique, based on Singer et al.'s approach. Participants included 27 AA YMSM. Focus groups explored how and where HIV transmission happens in Jackson, Mississippi. Result themes included: 1) location of sexual behaviors, 2) knowledge of geographic hotspots of HIV infection in Jackson, and 3) traveling to meet partners: at home and away. HIV transmission or "activity spaces" may be occurring outside identified HIV hot spots. Mixed geospatial and qualitative methods offered a comprehensive assessment of where HIV transmission occurs, and suggests that geographically circumscribed interventions may need to focus on where individuals living with HIV reside and in specific geographic locations where they engage in behaviors that raise their HIV acquisition risks.}, } @article {pmid33825569, year = {2021}, author = {Pusa, S and Isaksson, U and Sundin, K}, title = {Evaluation of the Implementation Process of a Family Systems Nursing Approach in Home Health Care: A Mixed-Methods Study.}, journal = {Journal of family nursing}, volume = {27}, number = {3}, pages = {235-249}, pmid = {33825569}, issn = {1552-549X}, mesh = {*Home Care Services ; Humans ; }, abstract = {To support the incorporation of Family Systems Nursing (FSN) in clinical practice, more understanding is needed about the implementation of FSN in home health practice settings. Thus, the aim of this study was to evaluate nurses' perspectives about the implementation process of Family Systems Nursing Conversations (FSNCs) in home health care. A mixed-methods research design was used, integrating qualitative and quantitative data, and using triangulation as a methodological metaphor. The Quality Implementation Framework (QIF) was applied to guide the implementation process, and Proctor et al.'s taxonomy of implementation outcomes was used to evaluate the process. The findings demonstrated that FSN implementation was in progress. Overall, acceptability and appropriateness of FSNCs were evaluated as positive by home health nurses; however, some obstacles were found relating to feasibility, adoption, and fidelity. These results contribute to an increased understanding of the process and challenges of implementing FSNCs in home health care.}, } @article {pmid33821793, year = {2021}, author = {Chantzichristos, D and Svensson, PA and Garner, T and Glad, CA and Walker, BR and Bergthorsdottir, R and Ragnarsson, O and Trimpou, P and Stimson, RH and Borresen, SW and Feldt-Rasmussen, U and Jansson, PA and Skrtic, S and Stevens, A and Johannsson, G}, title = {Identification of human glucocorticoid response markers using integrated multi-omic analysis from a randomized crossover trial.}, journal = {eLife}, volume = {10}, number = {}, pages = {}, pmid = {33821793}, issn = {2050-084X}, support = {2019-01112//Vetenskapsrådet/ ; SCAF/17/02/CSO_/Chief Scientist Office/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; ALFGBG-719531//The Swedish federal government under the LUA/ALF agreement/ ; MR/K010271/1/MRC_/Medical Research Council/United Kingdom ; 2015-02561//Vetenskapsrådet/ ; }, mesh = {Adipose Tissue/metabolism ; Adult ; Biomarkers/blood/*metabolism ; Case-Control Studies ; Cross-Over Studies ; Cross-Sectional Studies ; Denmark ; Female ; Glucocorticoids/*pharmacology ; Humans ; Leukocytes, Mononuclear/metabolism ; Male ; MicroRNAs/metabolism ; Middle Aged ; Plasma/metabolism ; Random Allocation ; Scotland ; Serum/metabolism ; Single-Blind Method ; Sweden ; *Transcriptome ; Young Adult ; }, abstract = {BACKGROUND: Glucocorticoids are among the most commonly prescribed drugs, but there is no biomarker that can quantify their action. The aim of the study was to identify and validate circulating biomarkers of glucocorticoid action.

METHODS: In a randomized, crossover, single-blind, discovery study, 10 subjects with primary adrenal insufficiency (and no other endocrinopathies) were admitted at the in-patient clinic and studied during physiological glucocorticoid exposure and withdrawal. A randomization plan before the first intervention was used. Besides mild physical and/or mental fatigue and salt craving, no serious adverse events were observed. The transcriptome in peripheral blood mononuclear cells and adipose tissue, plasma miRNAomic, and serum metabolomics were compared between the interventions using integrated multi-omic analysis.

RESULTS: We identified a transcriptomic profile derived from two tissues and a multi-omic cluster, both predictive of glucocorticoid exposure. A microRNA (miR-122-5p) that was correlated with genes and metabolites regulated by glucocorticoid exposure was identified (p=0.009) and replicated in independent studies with varying glucocorticoid exposure (0.01 ≤ p≤0.05).

CONCLUSIONS: We have generated results that construct the basis for successful discovery of biomarker(s) to measure effects of glucocorticoids, allowing strategies to individualize and optimize glucocorticoid therapy, and shedding light on disease etiology related to unphysiological glucocorticoid exposure, such as in cardiovascular disease and obesity.

FUNDING: The Swedish Research Council (Grant 2015-02561 and 2019-01112); The Swedish federal government under the LUA/ALF agreement (Grant ALFGBG-719531); The Swedish Endocrinology Association; The Gothenburg Medical Society; Wellcome Trust; The Medical Research Council, UK; The Chief Scientist Office, UK; The Eva Madura's Foundation; The Research Foundation of Copenhagen University Hospital; and The Danish Rheumatism Association.

CLINICAL TRIAL NUMBER: NCT02152553.}, } @article {pmid33820569, year = {2021}, author = {Marfak, A and Youlyouz-Marfak, I}, title = {An Excel program for calculating statistics presented in Marfak et al.'s article 'Improved RIDIT statistic approach provides more intuitive and informative interpretation of EQ-5D Data'.}, journal = {Health and quality of life outcomes}, volume = {19}, number = {1}, pages = {113}, pmid = {33820569}, issn = {1477-7525}, mesh = {Adult ; Aged ; Aged, 80 and over ; *Data Interpretation, Statistical ; *Disease ; Female ; *Health Status ; Humans ; Male ; Middle Aged ; *Quality of Life ; *Software ; Surveys and Questionnaires/*standards ; Therapeutics/*statistics & numerical data ; }, abstract = {The objective is to present and share an Excel program that we have developed to perform statistical analyses based on the Improved RIDIT approach of Marfak et al.'s article 'Improved RIDIT statistic approach provides more intuitive and informative interpretation of EQ-5D Data'.}, } @article {pmid33820493, year = {2022}, author = {Miklos, M and Jahnsen, R and Nyquist, A and Ullenhag, A}, title = {How transactional relations contribute to adaptive developmental outcomes when young people with disabilities participate in specially designed group programs - a scoping review.}, journal = {Scandinavian journal of occupational therapy}, volume = {29}, number = {8}, pages = {670-685}, doi = {10.1080/11038128.2021.1903989}, pmid = {33820493}, issn = {1651-2014}, mesh = {Adolescent ; Anthropology, Cultural ; Child ; Developmental Disabilities ; *Persons with Disabilities ; Humans ; Peer Group ; Qualitative Research ; Social Environment ; }, abstract = {BACKGROUND: Meta-synthesis can enhance our existing knowledge regarding experiences of participation in group-based programs designed for young people with disabilities.

AIM: This study aimed to identify the transactional relations between the social contexts in group programs and meaningful personal experiences and developmental processes for young people with disabilities.

METHOD: For this research, 4 electronic data-bases were searched, 3406 citations were reviewed, and 13 qualitative studies describing experiences of participation in specially designed group-based programs from the perspective of young people with disabilities were included. A meta-ethnographic approach was used to synthesise the data, and resulting categories were conceptualised in King et al.'s framework of transactional processes and adaptive development.

RESULTS: Nineteen categories across six themes describing: environment, social context, social mechanisms, personal processes, meaningful experiences, and outcomes demonstrated the dynamic interrelation between social context and personal processes. Peer group interaction was essential for exploring capacities and developing strategies.

CONCLUSION: This review highlights the important role of the peer group in transferring program experiences into the everyday life contexts of young people with disabilities. It may assist professionals who are considering the use of peer groups when planning participation-focussed programs aiming to facilitate personal development for young people with disabilities.}, } @article {pmid33810981, year = {2021}, author = {McInally, W and Gray-Brunton, C and Chouliara, Z and Kyle, RG}, title = {Experiences of living with cancer of adolescents and young adults and their families: A narrative review and synthesis.}, journal = {Enfermeria clinica}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.enfcli.2020.12.044}, pmid = {33810981}, issn = {2445-1479}, abstract = {INTRODUCTION: Adolescence is a critical life stage marked by significant physical, psychological, and social change. Cancer diagnosis during adolescence profoundly affects this experience for adolescents and young adults (AYA) and their families with an impact that continues throughout life. It is important to understand these experiences to ensure delivery of appropriate and high-quality supportive care. This narrative review critically appraised and synthesised qualitative literature that explored the experiences of AYAs and their families living with cancer.

METHOD: Narrative review and synthesis of qualitative research of AYAs' and their families' experiences of cancer. MEDLINE, CINAHL and PsycINFO were searched between February 2000 and September 2019 using search terms including "adolescent", "young people", "young adult", "cancer", "family", and "qualitative". Literature was appraised and synthesised using Popay et al.'s[1] framework.

RESULTS: 3016 articles were retrieved (Medline n=1298, CINAHL n=1632, PsycINFO n=86). Of these, 151 duplicates were removed. 2865 papers were screened with 121 abstracts considered for eligibility for inclusion. Eighteen papers met the inclusion criteria. Three inter-related themes were identified: being diagnosed with cancer; uncertainty - holding on to life and gaps in care delivery.

Few studies discuss the impact of cancer on the families of AYA living with cancer. Future research should explore this experience. By doing so the relational impact of cancer will be better understood as the basis of supportive family-centred care. PROSPERO Registration: CRD42017084148.}, } @article {pmid36101580, year = {2021}, author = {Suriyawongpaisal, P and Assanangkornchai, S and Saengow, U and Martinez Moyano, IJ and Patanavanich, R and Wongwatcharapaiboon, P and Aekplakorn, W and Thongtan, T}, title = {Intervening alcohol marketing to reduce harmful alcohol use and lessons learned from the theory of changes: Case studies in Thailand.}, journal = {Public health in practice (Oxford, England)}, volume = {2}, number = {}, pages = {100116}, pmid = {36101580}, issn = {2666-5352}, abstract = {OBJECTIVES: Globally, the burden of disease caused by alcohol use has been steadily increasing, including in Thailand. In this study, we aim to test the effectiveness of Anderson et al.'s suggested three approaches to change the collective social norms, which comprise of: (1) providing information and an understanding about alcohol use behaviour, its causes and distribution; (2) focusing strategies on groups rather than individuals; and (3) strengthening supportive laws, regulations and approaches.

STUDY DESIGN: We employed a mixed-methods approach. Evidence was gathered from literature review and in-depth interviews with key individuals who are responsible for community-based interventions to alcohol marketing strategies in Thailand.

METHODS: We chose to focus on two case studies in Nan and Surin provinces, where hospital-based longitudinal data (8 years) were available. Changes in casualties related to the harmful use of alcohol, resulting from interactions between community-based interventions and alcohol marketing during the time of annual festivals were investigated. We employed the theory of change (ToC) defined by Vogel to guide the data collection and analysis. We reviewed literature from online databases and grey literature to generate causal-loop diagrams.

RESULTS: We created a causal-loop diagram to describe the complexity of harmful alcohol use, its related factors, context, interventions and outcomes. Over the decade between 2006 and 2015, community-based strategies led to a substantial reduction of casualties (initially a 50% reduction, rising to an 80-90% reduction by the end of the study period) during the time of the festivals.

CONCLUSIONS: The reduction in injuries and fatalities could be a result of the concerted actions, including legal sanctions of alcohol beverage sales and advertisement, and public education to raise awareness and impart knowledge of the harmful use of alcohol. The actions were organised by a coalition of civil society, health professionals, public authorities and community leaders using hospital-based data on the adverse effects of harmful alcohol use to mobilise political support at the provincial level. The availability of long-term financial support as a catalytic source of funds and the presence of a comprehensive alcohol control act enabled framing and mobilisation of local resources and political support.}, } @article {pmid33779198, year = {2022}, author = {Meier, ST and Kim, S}, title = {Meta-regression analyses of relationships between burnout and depression with sampling and measurement methodological moderators.}, journal = {Journal of occupational health psychology}, volume = {27}, number = {2}, pages = {195-206}, doi = {10.1037/ocp0000273}, pmid = {33779198}, issn = {1939-1307}, mesh = {*Burnout, Professional/psychology ; Burnout, Psychological ; *Depression/psychology ; Female ; Humans ; Regression Analysis ; Reproducibility of Results ; }, abstract = {Despite 35 years of study, burnout researchers have failed to reach a consensus about whether burnout is distinct from depression. This review compiled reports containing zero-order correlations between scores on burnout, depression, and other measures of negative affect (NA) based on (a) reviews published by Kahill (1988), Glass and McKnight (1996), and Bianchi et al. (2015b), and (b) a search of PsycInfo using "depression" and "burnout" as search terms to find relevant studies published after 2014. The resulting data set contained 69 studies with 196 burnout-depression correlations based on 46,191 participants. We found an overall effect size of .492 between scores on burnout and depression measures (essentially equivalent to the .52 value reported in Koutsimani et al.'s, 2019, review) and an effect size of .546 between the Maslach Burnout Inventory emotional exhaustion scale and depression. Similarly, a correlation of .53 between burnout and NA measures is similar in size to the .46 correlation found by Koutsimani et al. Moderator analyses indicated that a larger burnout-depression correlation was associated with a higher proportion of female participants in a study, older participants, participants who had worked longer, and burnout measures with higher reliability estimates. The effects of age and years employed on the burnout-depression relationship suggest that repeated and negative work experiences are required for burnout to develop to the extent that its effects overlap with symptoms of depression. Conceptualizing the empirical relation between burnout and depression as a single point estimate may miss the more complex empirical picture. (PsycInfo Database Record (c) 2022 APA, all rights reserved).}, } @article {pmid33774826, year = {2021}, author = {Daniels, N and Gillen, P and Casson, K}, title = {Researcher practitioner engagement in health research: The development of a new concept.}, journal = {Research in nursing & health}, volume = {44}, number = {3}, pages = {534-547}, doi = {10.1002/nur.22128}, pmid = {33774826}, issn = {1098-240X}, mesh = {*Cooperative Behavior ; Decision Making ; Focus Groups ; *Health Personnel ; *Health Services Research ; Humans ; Internet ; Problem Solving ; *Research Personnel ; }, abstract = {The engagement of frontline practitioners in the production of research-derived knowledge is often advocated. Doing so can address perceived gaps between what is known from research and what happens in clinical practice. Engagement practices span a continuum, from co-production approaches underpinned by principles of equality and power sharing to those which can minimalize practitioners' contributions to the knowledge production process. We observed a conceptual gap in published healthcare literature that labels or defines practitioners' meaningful contribution to the research process. We, therefore, aimed to develop the concept of "Researcher Practitioner Engagement" in the context of academically initiated healthcare research in the professions of nursing, midwifery, occupational therapy, physiotherapy, and speech and language therapy. Guided by Schwartz-Barcott et al.'s hybrid model of concept development, published examples were analyzed to establish the attributes, antecedents, and consequences of this type of engagement. Academic researchers (n = 17) and frontline practitioners (n = 8) with relevant experience took part in online focus groups to confirm, eliminate, or elaborate on these proposed concept components. Combined analysis of theoretical and focus group data showed that the essence of this form of engagement is that practitioners' clinical knowledge is valued from a study's formative stages. The practitioner's clinical perspectives inform problem-solving and decision-making in study activities and enhance the professional and practice relevance of a study. The conceptual model produced from the study findings forms a basis to guide engagement practices, future concept testing, and empirical evaluation of engagement practices.}, } @article {pmid33765520, year = {2021}, author = {Petrizzo, I and Castaldi, E and Anobile, G and Bassanelli, S and Arrighi, R}, title = {Time and numerosity estimation in peripersonal and extrapersonal space.}, journal = {Acta psychologica}, volume = {215}, number = {}, pages = {103296}, doi = {10.1016/j.actpsy.2021.103296}, pmid = {33765520}, issn = {1873-6297}, mesh = {Adult ; Arm ; Humans ; *Personal Space ; *Space Perception ; }, abstract = {The representation of space, time and number is believed to rely on a common encoding system developed to support action guidance. While the ecological advantage of such a shared system is evident when objects are located within the region of space we can act on (known as peri-personal space), it is less obvious in the case of objects located beyond our arms' reach. In the current study we investigated whether and to what extent the distance of the stimuli from the observer affects the perception of duration and numerosity. We first replicated Anelli et al.'s (2015) experiment by asking adult participants to perform a duration reproduction task with stimuli of different sizes displayed in the peri- or extra-personal space, and then applied the same paradigm to a non-symbolic numerosity estimation task. Results show that, independently of size, duration estimates were overestimated when visual stimuli were presented in the extra-personal space, replicating previous findings. A similar effect was also found for numerosity perception, however overestimation for far stimuli was much smaller in magnitude and was accounted by the difference in perceived size between stimuli presented in peripersonal or extrapersonal space. Overall, these results suggest that, while the processing of temporal information is robustly affected by the position of the stimuli in either the peri- or extra-personal space, numerosity perception is independent from stimulus distance. We speculate that, while time and numerosity may be encoded by a shared system in the peri-personal space (to optimize action execution), different and partially independent mechanisms may underlie the representation of time and numerosity in extra-personal space. Furthermore, these results suggest that investigating magnitude perception across spatial planes (where it is or is not possible to act) may unveil processing differences that would otherwise pass unnoticed.}, } @article {pmid33759210, year = {2021}, author = {Davies, EB and Bergin, AD}, title = {Commentary: Let's get digital: a commentary on Halldorsson et al.'s call for more rigorous development and evaluation of immersive digital interventions for children and young people's mental health.}, journal = {Journal of child psychology and psychiatry, and allied disciplines}, volume = {62}, number = {5}, pages = {606-609}, doi = {10.1111/jcpp.13423}, pmid = {33759210}, issn = {1469-7610}, support = {PDF-2016-09-092/DH_/Department of Health/United Kingdom ; RP-2014-05-003/DH_/Department of Health/United Kingdom ; RP-2014-04-018/DH_/Department of Health/United Kingdom ; }, mesh = {Adolescent ; Child ; Humans ; *Mental Health ; }, abstract = {In the JCPP Annual Research Review for 2021, Halldorsson and colleagues (2021) present a systematic review of applied games and virtual reality interventions for treating mental health problems in children and young people, looking at the effectiveness of interventions upon mental health outcomes but also on the experience of using such interventions. In this commentary, we highlight a number of considerations in understanding what research has been achieved so far, and ideas for what needs to be looked at next in further advancing this field.}, } @article {pmid33756070, year = {2021}, author = {La Hoz, RM and Danziger-Isakov, LA and Klassen, DK and Michaels, MG}, title = {Risk and reward: Balancing safety and maximizing lung donors during the COVID-19 pandemic.}, journal = {American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons}, volume = {21}, number = {8}, pages = {2635-2636}, pmid = {33756070}, issn = {1600-6143}, support = {250-2019-00001C//United Network for Organ Sharing (UNOS)/ ; //US Department of Health and Human Services/ ; /HRSA/HRSA HHS/United States ; //Healthcare Systems Bureau/ ; //Division of Transplantation/ ; /HRSA/HRSA HHS/United States ; }, mesh = {*COVID-19 ; Humans ; Lung ; *Pandemics ; Reward ; SARS-CoV-2 ; }, abstract = {In response to Kaul et al.’s article (page 2885), the editorialists recommend testing lower respiratory tract samples from potential deceased lung donors for SARS-CoV-2 to mitigate the risk of donor derived disease.}, } @article {pmid33753159, year = {2022}, author = {Lowe, MR}, title = {Commentary on: "What is restrained eating and how do we identify it?": Unveiling the elephant in the room.}, journal = {Appetite}, volume = {168}, number = {}, pages = {105221}, doi = {10.1016/j.appet.2021.105221}, pmid = {33753159}, issn = {1095-8304}, mesh = {*Binge-Eating Disorder ; *Bulimia ; Diet, Reducing ; Eating ; Feeding Behavior ; Humans ; Hyperphagia ; }, abstract = {This paper is a commentary on Polivy, Herman and Mills' (2020) article, entitled "What is restrained eating and how do we identify it?". Polivy et al.'s paper makes a useful contribution by providing guidelines to researchers for choosing the most appropriate measure of restraint for their research questions. However, the authors assume that restrained eating can be appropriately conceptualized as a trait, an assumption I question. They also assume that restrained eating has a causal influence on the outcomes (e.g., counterregulatory eating, negative affect eating, binge eating) with which it has been associated, which I also question. Finally, they ignored a second prominent model for conceptualizing dieting behavior, the Three-Factor Model of Dieting. The Three-Factor Model decomposes the construct of restrained eating into two types of dieting (current weight loss dieting and weight suppression) that do appear to be causally related to eating control and one type (restrained eating to avoid excessive consumption) that modulates likelihood of overeating but does not cause it. I conclude by noting that scientific progress is best served by promoting, not avoiding, discussion and debate about a multiplicity of perspectives on topics of interest, especially when incompatible hypotheses and data exist on such topics.}, } @article {pmid33751212, year = {2021}, author = {do Couto, MC and de Sousa Fernandes, MS and Dos Santos, TM}, title = {Comment: Kay et al.'s (2020) Isokinetic eccentric exercise substantially improves mobility, muscle strength, and size, but not postural sway metrics in older adults with limited regression observed following a detraining period. Eur J Appl Physiol.}, journal = {European journal of applied physiology}, volume = {121}, number = {6}, pages = {1795-1796}, pmid = {33751212}, issn = {1439-6327}, mesh = {Aged ; *Benchmarking ; Exercise Therapy ; Humans ; *Muscle Strength ; }, } @article {pmid33740588, year = {2021}, author = {Surachman, A and Jenkins, AIC and Santos, AR and Almeida, DM}, title = {Socioeconomic status trajectories across the life course, daily discrimination, and inflammation among Black and white adults.}, journal = {Psychoneuroendocrinology}, volume = {127}, number = {}, pages = {105193}, pmid = {33740588}, issn = {1873-3360}, support = {UL1 TR001409/TR/NCATS NIH HHS/United States ; UL1 RR025011/RR/NCRR NIH HHS/United States ; F31 MD015215/MD/NIMHD NIH HHS/United States ; U19 AG051426/AG/NIA NIH HHS/United States ; UL1 TR001881/TR/NCATS NIH HHS/United States ; T32 AG049676/AG/NIA NIH HHS/United States ; UL1 TR002373/TR/NCATS NIH HHS/United States ; P01 AG020166/AG/NIA NIH HHS/United States ; }, mesh = {Adult ; Black or African American/*statistics & numerical data ; Aged ; Biomarkers/analysis ; C-Reactive Protein/analysis ; Female ; Fibrinogen/analysis ; Humans ; Inflammation/*epidemiology ; Interleukin-6/analysis ; *Life Change Events ; Male ; Middle Aged ; Racism/*statistics & numerical data ; Social Class ; *Social Status ; United States ; White People/*statistics & numerical data ; }, abstract = {OBJECTIVE: This study replicates and expands Surachman et al.'s (2020) findings documenting socioeconomic status (SES) trajectories across the life course in an independent sample of Black (majority recruited from Milwaukee, WI) and white adults in the United States. We extend this work by examining whether SES trajectories and daily discrimination are independently associated with markers of inflammation.

METHOD: Data were from 215 Black adults (188 recruited from Milwaukee, WI; 27 recruited from across the continental US) and 985 white adults (7 recruited from Milwaukee, WI; 978 recruited from across the continental US) who completed the baseline interview and biomarker assessment during the second wave of the Midlife in the United States (MIDUS) Study (ages = 34-84). SES life course trajectories were examined using latent class analysis based on objective (e.g., income and education) and subjective (e.g., social status and financial strain) indicators of SES. The association between life course SES trajectories and daily discrimination with markers of inflammation (IL-6, CRP, fibrinogen) were examined using multiple linear regression analyses, controlling for demographic, psychological, behavioral, and health-related covariates.

RESULTS: Black and white participants showed different patterns of life course SES trajectories. Among Black participants, the trajectories were Objectively Stable Low (45.16%), Downwardly Mobile (18.05%), and Upwardly Mobile (36.79%). Compared to the Upwardly Mobile, the Objectively Stable Low class showed elevated IL-6 after controlling for all covariates. Further, daily discrimination, but not SES trajectories, was significantly associated with CRP and fibrinogen after controlling for demographic, psychological, and behavioral covariates. White participants' experiences of life course SES trajectories were characterized as Objectively Stable Low (7.02%), Subjectively Downward (12.48%), Upwardly Mobile (39.99%), and Stable High (40.51%). Among white participants, SES trajectories, but not daily discrimination, were associated with all markers of inflammation (controlling for age and sex).

DISCUSSION: Consistent with the fundamental cause theory, multiple independent pathways link SES trajectories across the life course and daily discrimination to racial disparities in IL-6, CRP, and fibrinogen.}, } @article {pmid33735197, year = {2021}, author = {Mandel, DR and Irwin, D}, title = {On measuring agreement with numerically bounded linguistic probability schemes: A re-analysis of data from Wintle, Fraser, Wills, Nicholson, and Fidler (2019).}, journal = {PloS one}, volume = {16}, number = {3}, pages = {e0248424}, pmid = {33735197}, issn = {1932-6203}, mesh = {Adult ; *Communication ; Data Analysis ; *Decision Making ; Humans ; Language ; Research/standards ; *Terminology as Topic ; *Uncertainty ; }, abstract = {Across a wide range of domains, experts make probabilistic judgments under conditions of uncertainty to support decision-making. These judgments are often conveyed using linguistic expressions (e.g., x is likely). Seeking to foster shared understanding of these expressions between senders and receivers, the US intelligence community implemented a communication standard that prescribes a set of probability terms and assigns each term an equivalent numerical probability range. In an earlier PLOS ONE article, [1] tested whether access to the standard improves shared understanding and also explored the efficacy of various enhanced presentation formats. Notably, they found that embedding numeric equivalents in text (e.g., x is likely [55-80%]) substantially outperformed the status-quo approach in terms of the percentage overlap between participants' interpretations of linguistic probabilities (defined in terms of the numeric range equivalents they provided for each term) and the numeric ranges in the standard. These results have important prescriptive implications, yet Wintle et al.'s percentage overlap measure of agreement may be viewed as unfairly punitive because it penalizes individuals for being more precise than the stipulated guidelines even when the individuals' interpretations fall perfectly within the stipulated ranges. Arguably, subjects' within-range precision is a positive attribute and should not be penalized in scoring interpretive agreement. Accordingly, in the present article, we reanalyzed Wintle et al.'s data using an alternative measure of percentage overlap that does not penalize in-range precision. Using the alternative measure, we find that percentage overlap is substantially elevated across conditions. More importantly, however, the effects of presentation format and probability level are highly consistent with the original study. By removing the ambiguity caused by Wintle et al.'s unduly punitive measure of agreement, these findings buttress Wintle et al.'s original claim that the methods currently used by intelligence organizations are ineffective at coordinating the meaning of uncertainty expressions between intelligence producers and intelligence consumers. Future studies examining agreement between senders and receivers are also encouraged to reflect carefully on the most appropriate measures of agreement to employ in their experiments and to explicate the bases for their methodological choices.}, } @article {pmid33734989, year = {2021}, author = {Acuña, V and Otto, A and Cavieres, A and Villalobos, H}, title = {Efficacy of Metacognitive Training in a Chilean Sample of People with Schizophrenia.}, journal = {Revista Colombiana de psiquiatria}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.rcp.2020.12.006}, pmid = {33734989}, issn = {2530-3120}, abstract = {INTRODUCTION: Moritz et al.'s metacognitive training (MCT), a new development of cognitive therapy, is a manualized group training program, designed to correct cognitive biases involved in the formation and maintenance of psychotic symptoms, especially delusions. We report on the efficacy of MCT in a Chilean sample of people with schizophrenia.

METHODS: 50 outpatients from the Hospital Del Salvador at Valparaíso, Chile, were randomly assigned to the intervention group (MCT), or the control group, that only received treatment as usual (TAU). Subjects were assessed at the beginning and end of the study with the Positive and Negative Syndrome Scale (PANSS), Cognitive Biases Questionnaire for Psychosis (CBQ-P) and Beck Cognitive Insight Scale (BCIS).

RESULTS: In the MCT group, we found larger, statistically significant improvements, in symptoms, cognitive biases and cognitive insight, than in the control group. However, after a direct comparison of both groups, only the improvement in psychotic symptoms for the MCT group, remained significantly different.

CONCLUSIONS: The results of this study suggest superiority of MCT over TAU in the amelioration of positive symptoms. We could not, however demonstrate its superiority in the improvement of the cognitive biases and cognitive insight.}, } @article {pmid33734787, year = {2021}, author = {Portwood, SG and Lawler, MJ and Roberts, MC}, title = {Science, practice, and policy related to adverse childhood experiences: Framing the conversation.}, journal = {The American psychologist}, volume = {76}, number = {2}, pages = {181-187}, doi = {10.1037/amp0000809}, pmid = {33734787}, issn = {1935-990X}, mesh = {Adolescent ; Adult ; *Adverse Childhood Experiences ; Child ; *Health Policy ; Humans ; *Mental Health ; *Public Health ; }, abstract = {Adverse childhood experiences (ACEs) detrimentally affect health outcomes in childhood, adolescence, and adulthood. Over the past 2 decades, the recognition of ACEs by scientists and professionals across disciplines, policymakers, and the public has evolved and expanded. Although the initial articulation of ACEs in Felitti et al.'s landmark study has formed the basis of subsequent investigations on the long-term impact of childhood adversities on health and health risk behaviors, a wider public health framework, inclusive of psychology and other social sciences, also shapes current conceptualizations, research, practice, and policies. This article provides an overview of the special issue Adverse Childhood Experiences: Translating Research to Action. Given the rapid expansion and widespread application of ACEs, this special issue was developed to articulate critical concepts, to demonstrate the significance and relevance of psychological research and practice, and to catalyze further efforts to develop effective programs and policies informed by science. The 15 articles included reflect the continuum of critical work being conducted in research, practice, intervention and prevention programs, and public policy and serve to synthesize the growing body of empirical evidence. The overarching themes that emerged are framed as 3 essential questions: (a) How broadly should ACEs be defined?, (b) How should ACEs be assessed?, and (c) How can ACEs science translate into high quality services? As illustrated in these articles, policy and practice applications deriving from psychology as a hub science can substantially benefit the health and mental health of children, adolescents, and adults. (PsycInfo Database Record (c) 2021 APA, all rights reserved).}, } @article {pmid33710318, year = {2021}, author = {Schnake-Mahl, AS and Bilal, U}, title = {Schnake-Mahl and Bilal Respond to "Structural Racism and COVID-19 Mortality in the US".}, journal = {American journal of epidemiology}, volume = {190}, number = {8}, pages = {1447-1451}, doi = {10.1093/aje/kwab058}, pmid = {33710318}, issn = {1476-6256}, support = {DP5 OD026429/OD/NIH HHS/United States ; }, mesh = {*COVID-19 ; Ethnicity ; Health Status Disparities ; Humans ; *Racism ; SARS-CoV-2 ; }, abstract = {In their commentary, Zalla et al. (Am J Epidemiol. 2021;190(8):1439-1446) argue that the approach taken by the Centers for Disease Control and Prevention, comparing the proportion of coronavirus disease 2019 (COVID-19) deaths by race/ethnicity with a weighted population distribution, ignores how systemic racism structures the composition of places. While the Centers for Disease Control and Prevention have abandoned their measure, they did so because of the changing geographic distribution of COVID-19, not because the measure underestimates racial disparities. We further Zalla et al.'s argument, advocating for a relational approach to estimating COVID-19 racial inequities that integrates the reciprocal relationship between context and composition through the interaction of places and people over time. To support our argument, we present a series of figures exploring the heterogeneous relationships between places, people, and time, using publicly available, US county-level COVID-19 mortality data from February to December 2020 from Johns Hopkins University. Longitudinal and more geographically granular data that allows for disaggregation by person, place, and time will improve our estimation and understanding of inequities in COVID-19.}, } @article {pmid33705181, year = {2021}, author = {Bailey, PE and Ebner, NC and Stine-Morrow, EAL}, title = {Introduction to the special issue on prosociality in adult development and aging: Advancing theory within a multilevel framework.}, journal = {Psychology and aging}, volume = {36}, number = {1}, pages = {1-9}, doi = {10.1037/pag0000598}, pmid = {33705181}, issn = {1939-1498}, mesh = {Adult ; Aged ; Aging ; *Altruism ; Humans ; }, abstract = {Prosociality refers to a broad set of behavioral, motivational, cognitive, affective, and social processes that contribute to, and/or are focused on, the welfare of others. This overview summarizes 10 articles included in the special issue on this topic. In discussing this research relative to existing theories, we situate this work within Penner et al.'s (Annual Review of Psychology, 56, 2005, 365-392) multilevel framework that recognizes distinct yet integrated levels of analysis to characterize micro- (i.e., intraindividual), meso- (i.e., interpersonal), and macro- (i.e., sociocultural and organizational contexts) level effects. While there is some evidence for lifespan continuity in prosocial dispositions at the micro level, the influences of long-term learning and socialization processes at the meso and macro levels are likely to be maximized in older age. Aside from formal voluteering, the adult lifespan development of prosociality has only recently received attention, especially with respect to influences beyond the micro level. This special issue encompasses research examining developmental change and stability in prosociality that collectively cuts across levels of analysis to inform theories in both adult development and aging and prosociality more generally. We propose future directions that take an integrative approach to understanding the development of prosociality by considering interactions among micro, meso, and macro levels. (PsycInfo Database Record (c) 2021 APA, all rights reserved).}, } @article {pmid33694333, year = {2021}, author = {Duangchan, C and Matthews, AK}, title = {Application of Ferrans et al.'s conceptual model of health-related quality of life: A systematic review.}, journal = {Research in nursing & health}, volume = {44}, number = {3}, pages = {490-512}, doi = {10.1002/nur.22120}, pmid = {33694333}, issn = {1098-240X}, mesh = {*Functional Status ; Humans ; *Models, Theoretical ; Quality of Life/*psychology ; }, abstract = {Ferrans, Zerwic, Wilbur, and Larson proposed the conceptual model of health-related quality of life (HRQOL) in 2005 to explicate the constructs associated with HRQOL and to describe the associations among those constructs. In this systematic review, the authors aimed to describe empirical studies that used Ferrans et al.'s model and to examine the evidence related to the hypothesized model concepts. This review followed Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Relevant articles were identified using Crossref, CINAHL, and PubMed. To be included, studies had to employ the model as a theoretical framework and be published in English between 2005 and 2020. Type of theory use was coded using four designations: informed by theory, applied theory, testing theory, and building theory. Thirty-one studies were included. Most studies involved adult patients with chronic illnesses (n = 20) and were conducted in Western countries (n = 22). The most common type of theory use was testing theory (74.19%). Among the seven concepts in Ferrans et al.'s model, all 20 hypothesized associations were tested and 19 were supported by study results. The three associations most frequently supported were between symptoms and functional status (n = 13), environmental characteristics and quality of life (n = 10), and individual characteristics and functional status (n = 8). No studies found an association between environmental characteristics and biological function. Our review found that Ferrans et al.'s model has been used extensively to guide HRQOL research. An emerging body of research provides preliminary support for the associations hypothesized in the model. Additional research is needed to confirm the hypothesized associations among model concepts.}, } @article {pmid33679981, year = {2021}, author = {Karobari, MI and Parveen, A and Mirza, MB and Makandar, SD and Nik Abdul Ghani, NR and Noorani, TY and Marya, A}, title = {Root and Root Canal Morphology Classification Systems.}, journal = {International journal of dentistry}, volume = {2021}, number = {}, pages = {6682189}, pmid = {33679981}, issn = {1687-8728}, abstract = {INTRODUCTION: While there are many root morphology classification systems with their own distinct advantages, there are many shortcomings that come along with each system.

OBJECTIVES: The aim of this review was to compare the various root and root canal morphology classifications, their advantages, limitations, and clinical and research implications. Data Sources and Selection. An extensive literature search was conducted on PubMed and Scopus to identify the published data on root and root canal classification systems published until 1 May 2020 using keywords, root canal classification system, classification systems for root canals, and root morphology. The related literature was reviewed and then summarized. Data Synthesis. Several studies have analysed and detailed root and root canal classifications and further added new subsystems, works of Weine et al. (1969) and Vertucci et al. (1974). Besides, Sert and Bayirli (2004) added supplementary types to Vertucci's classification system. A new classification was most recently introduced by Ahmed et al. (2017) involving the use of codes for tooth numbering, number of roots, and canal configuration.

CONCLUSIONS: Weine et al. classified only single-rooted teeth, without considering multirooted teeth and complex configurations. Vertucci's classification included complex configurations, with Sert and Bayirli adding further complex supplemental types. Ahmed et al.'s classification simplifies classifying root and canal morphology while overcoming the limitations of several previous classification systems making it beneficial for implementation in dental schools.}, } @article {pmid33678613, year = {2021}, author = {Tamiya, S}, title = {[Multilingualism and the Reserve Theory].}, journal = {Brain and nerve = Shinkei kenkyu no shinpo}, volume = {73}, number = {3}, pages = {217-222}, doi = {10.11477/mf.1416201743}, pmid = {33678613}, issn = {1881-6096}, mesh = {Brain ; *Cognitive Reserve ; Executive Function ; Humans ; Language ; *Multilingualism ; }, abstract = {It has been well recognized that patients with comparable dementia severity may show different levels of brain pathology. This is commonly explained by cognitive or brain reserve theory: patients with more reserve can tolerate more severe brain pathologies because the reserve can compensate for the neuropathological processes. Various life experiences contribute to the reserve, one of which may be multilingualism. Multilinguals need to select the appropriate language for a conversational partner and to keep other languages inactivated. Such experiences reinforce the multilingual executive functions, and change neuroanatomical and neurophysiological features of the brain, which some researchers propose can serve as a reserve and prevent dementia. The earliest such report was Bialystok et al.'s (2007) paper, which demonstrated multilinguals showing signs of dementia approximately four years later than monolinguals. This finding seemed to support the hypothesis of multilingualism as a reserve, and was followed by many other reports testing the same. Notwithstanding the initial excitement, the data obtained so far have been mixed at best in terms of the possibility of multilingualism influencing the neuropathological processes of dementia. This paper summarizes recent findings on multilingualism and the reserve theory, and discusses identified research issues that need to be resolved.}, } @article {pmid33678061, year = {2021}, author = {Spielmans, GI}, title = {Re-Analyzing Phase III Bremelanotide Trials for "Hypoactive Sexual Desire Disorder" in Women.}, journal = {Journal of sex research}, volume = {58}, number = {9}, pages = {1085-1105}, doi = {10.1080/00224499.2021.1885601}, pmid = {33678061}, issn = {1559-8519}, mesh = {Female ; Humans ; *Libido ; Peptides, Cyclic ; *Sexual Dysfunctions, Psychological/drug therapy ; alpha-MSH ; }, abstract = {Kingsberg et al. described results from two 24-week Phase III trials of bremelanotide for treating hypoactive sexual desire disorder (HSDD) in women. 72.72% of protocol-listed outcomes were not reported by Kingsberg et al., who provided results of 15 secondary measures which were not listed in the study protocols. None of their efficacy outcomes were reported in line with CONSORT data reporting standards and no secondary outcome had a stated rationale or cited evidence of validity. My meta-analysis of the trials' data, based on the FDA New Drug Application, found similar results to Kingsberg et al. However, Kingsberg et al. did not report that a) adverse event-induced study discontinuation was substantially higher on bremelanotide: OR = 11.98, 95% CI = 3.74-38.37, NNH: 6 or b) participants preferred placebo, measured by the combination of both 1) completing a clinical trial and 2) electing to participate in the follow-up open-label study (OR = 0.30, 95% CI = .24-.38, NNH: 4). Bremelanotide's modest benefits on incompletely reported post-hoc measures of questionable validity in combination with participants substantially preferring to take placebo suggest that the drug is generally not useful. Kingsberg et al.'s data reporting and measurement practices were incomplete and lacked transparency.}, } @article {pmid33676758, year = {2022}, author = {Potter, AL and Jeffrey Yang, CF}, title = {Commentary: The tid(al)s are turning toward lower volumes.}, journal = {The Journal of thoracic and cardiovascular surgery}, volume = {163}, number = {4}, pages = {1587-1588}, doi = {10.1016/j.jtcvs.2021.01.040}, pmid = {33676758}, issn = {1097-685X}, } @article {pmid33667138, year = {2021}, author = {Crawford, JT and Ruscio, J}, title = {Asking People to Explain Complex Policies Does Not Increase Political Moderation: Three Preregistered Failures to Closely Replicate Fernbach, Rogers, Fox, and Sloman's (2013) Findings.}, journal = {Psychological science}, volume = {32}, number = {4}, pages = {611-621}, doi = {10.1177/0956797620972367}, pmid = {33667138}, issn = {1467-9280}, mesh = {Comprehension ; Humans ; Knowledge ; *Policy ; *Politics ; }, abstract = {Fernbach et al. (2013) found that political extremism and partisan in-group favoritism can be reduced by asking people to provide mechanistic explanations for complex policies, thus making their lack of procedural-policy knowledge salient. Given the practical importance of these findings, we conducted two preregistered close replications of Fernbach et al.'s Experiment 2 (Replication 1a: N = 306; Replication 1b: N = 405) and preregistered close and conceptual replications of Fernbach et al.'s Experiment 3 (Replication 2: N = 343). None of the key effects were statistically significant, and only one survived a small-telescopes analysis. Although participants reported less policy understanding after providing mechanistic policy explanations, policy-position extremity and in-group favoritism were unaffected. That said, well-established findings that providing justifications for prior beliefs strengthens those beliefs, and well-established findings of in-group favoritism, were replicated. These findings suggest that providing mechanistic explanations increases people's recognition of their ignorance but is unlikely to increase their political moderation, at least under these conditions.}, } @article {pmid33662151, year = {2022}, author = {Pepke, ML and Eisenberg, DTA}, title = {On the comparative biology of mammalian telomeres: Telomere length co-evolves with body mass, lifespan and cancer risk.}, journal = {Molecular ecology}, volume = {31}, number = {23}, pages = {6286-6296}, doi = {10.1111/mec.15870}, pmid = {33662151}, issn = {1365-294X}, mesh = {Animals ; Longevity/genetics ; *Telomerase/genetics/metabolism ; Phylogeny ; Mammals/genetics ; *Neoplasms/genetics ; Telomere/genetics/metabolism ; Biology ; Cellular Senescence/genetics ; }, abstract = {Telomeres, the short repetitive DNA sequences that cap the ends of linear chromosomes, shorten during cell division and are implicated in senescence in most species. Telomerase can rebuild telomeres but is repressed in many mammals that exhibit replicative senescence, presumably as a tumour suppression mechanism. It is therefore important to understand the co-evolution of telomere biology and life-history traits that has shaped the diversity of senescence patterns across species. Gomes et al. previously produced a large data set on telomere length (TL), telomerase activity, body mass and lifespan among 57 mammal species. We re-analysed their data using the same phylogenetic multiple regressions and with several additional analyses to test the robustness of the findings. We found substantial inconsistencies in our results compared to Gomes et al.'s. Consistent with Gomes et al. we found an inverse association between TL and lifespan. Contrary to the analyses in Gomes et al., we found a generally robust inverse association between TL and mass, and only weak nonrobust evidence for an association between telomerase activity and mass. These results suggest that shorter TL may have been selected for in larger and longer lived species, probably as a mechanism to suppress cancer. We support this hypothesis by showing that longer telomeres predict higher cancer risk across 22 species. Furthermore, we find that domesticated species have longer telomeres. Our results call into question past interpretations of the co-evolution of telomere biology and life-history traits and stress the need for careful attention to model construction.}, } @article {pmid33640224, year = {2022}, author = {Katayanagi, J and Iida, T and Hayamizu, A and Matsumoto, K and Furukawa, H and Konuma, H and Yanase, T and Ozeki, S}, title = {Pre-existing vertebral fracture is a risk factor for postoperative proximal junctional fracture after adult spinal deformity surgery: A propensity score-matched analysis.}, journal = {Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association}, volume = {27}, number = {2}, pages = {308-316}, doi = {10.1016/j.jos.2021.01.003}, pmid = {33640224}, issn = {1436-2023}, mesh = {Adult ; Female ; Humans ; *Kyphosis/diagnostic imaging/etiology/surgery ; Middle Aged ; Propensity Score ; Quality of Life ; Retrospective Studies ; Risk Factors ; *Spinal Fractures/diagnostic imaging/etiology/surgery ; *Spinal Fusion/adverse effects ; }, abstract = {BACKGROUND: Corrective surgery for adult spinal deformity has recently been increasingly performed because of aging populations and advances in minimally invasive surgery. Low bone mineral density is a major contributor to proximal junctional kyphosis after spinal long fusion. Assessment for low bone mineral density ideally involves both dual energy X-ray absorptiometry and identification of pre-existing vertebral fractures, the latter, requiring only standard equipment, being performed more frequently. We therefore aimed to examine the impact of pre-existing vertebral fractures on the incidence of type 2 proximal junctional kyphosis, including proximal junctional fracture and failure, after corrective surgery for adult spinal deformity.

METHODS: We performed a retrospective, single institution study of 106 women aged over 50 years who had undergone corrective long spinal fusion for severely symptomatic spinal deformity from 2014 to 2017. We allocated them to three groups (with and without pre-existing vertebral fractures and with severe [Grades 2-3 according to Genant et al.'s classification] preexisting vertebral fractures) and used propensity score matching to minimize bias. The primary outcome was postoperative proximal junctional fracture and the secondary outcome proximal junctional kyphosis/failure.

RESULTS: The primary and secondary endpoints were achieved significantly more often in the 28 patients with than in the 78 without preexisting vertebral fractures (total 41). The former group was also significantly older and had greater pelvic tilt and fewer fused segments than those without vertebral fractures. After propensity score matching, the incidences of the endpoints did not differ with pre-existing vertebral fracture status; however, patients with severe vertebral fractures more frequently had proximal junctional fractures postoperatively. Postoperative improvements in health-related quality of life scores did not differ with pre-existing vertebral fracture status.

CONCLUSIONS: Severe pre-existing vertebral fractures are a risk factor for proximal junctional fracture after correction of adult spinal deformity.}, } @article {pmid33639979, year = {2021}, author = {Kletter, M and Harris, B and Brown, C}, title = {Outcomes, mechanisms and contextual factors of positive psychology interventions for health workers: a systematic review of global evidence.}, journal = {Human resources for health}, volume = {19}, number = {1}, pages = {24}, pmid = {33639979}, issn = {1478-4491}, support = {/DH_/Department of Health/United Kingdom ; }, mesh = {*Health Personnel ; Health Workforce ; Humans ; *Psychology, Positive ; Quality Improvement ; }, abstract = {BACKGROUND: Interventions using positive psychology (PP), which build on positive qualities of healthcare personnel and institutions, could potentially enhance organisational performance in healthcare. The aim of this systematic review was to identify if PP interventions have an impact on organisational performance of healthcare personnel, and if so, how this impact can be achieved. We developed a logic model to explain the impact of PP interventions on organisational performance.

METHODS: We searched Web of Science, Medline, Psychinfo, Embase, Scopus and CINAHL (from inception until March 2019) and references of included articles to identify studies that evaluated the impact of a PP intervention for health personnel. Study quality was assessed using the SQUIRE checklist for quality improvement studies. Data were extracted about study details, setting, participants, intervention, method of evaluation and results. Outcomes, mechanisms and contexts were coded in nVivo. Data synthesis was guided by Lewis' theory of the impact of PP interventions on organisational performance and Kneale et al.'s method for logic model development. Collected data were integrated into a logic model explaining initial inputs, processes, and intermediate outcomes of PP interventions that lead to improved organisational performance in healthcare settings.

RESULTS: We retrieved 4638 articles and identified five through references of included articles of which 29 studies (31 articles) met our inclusion criteria. Most articles were of low quality (n = 19) and outcome measures varied widely. We identified 54 different outcomes of PP interventions, including 'improved well-being' and 'improved interaction and support'. Forty-nine mechanisms were identified including 'recognising and reframing negative interpretations'. Twenty four contextual factors were identified of which seven acted as barriers. 'Managerial support' was a facilitator mentioned in eight studies. All identified outcomes, mechanisms and contextual factors were integrated into a logic model explaining how interventions using PP can impact organisational performance in healthcare.

CONCLUSION: Few identified outcomes were statistically significant, however, trends in both quantitative and qualitative outcomes show that PP interventions can increase well-being and interaction and support and thus improve organisational performance in healthcare. The developed logic model can be used in the implementation and evaluation of interventions using PP for health personnel.}, } @article {pmid33638930, year = {2021}, author = {Gärtner, BC and Sester, M}, title = {Diversity of antibody responses after influenza infection or vaccination-Needed or nice to have?.}, journal = {American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons}, volume = {21}, number = {8}, pages = {2631-2632}, pmid = {33638930}, issn = {1600-6143}, mesh = {Antibodies, Viral ; Antibody Formation ; Humans ; *Influenza, Human/prevention & control ; Vaccination ; }, abstract = {Gärtner and Sester contextualize recent findings on natural and vaccine‐induced immunity towards influenza in transplant recipients including implications for other vaccines. Hirzel et al.'s article is on page 2709.}, } @article {pmid33635027, year = {2020}, author = {Gao, T and Zhang, X and Gurd, B and Liu, Z}, title = {From self-management to a systemized process: the implementation of lean management in a Chinese hospital's pharmacy intravenous admixture services center.}, journal = {Leadership in health services (Bradford, England)}, volume = {33}, number = {4}, pages = {325-337}, doi = {10.1108/LHS-12-2019-0085}, pmid = {33635027}, issn = {1751-1887}, mesh = {China ; Hospitals ; Humans ; Leadership ; *Pharmacy ; *Self-Management ; }, abstract = {PURPOSE: The purpose of this paper is to explore the importance of lean leadership in an implementation in a Chinese hospital, considering a particular focus on the attitudes of nursing professionals while identifying specific cultural or institutional factors in China that might affect the implementation.

DESIGN/METHODOLOGY/APPROACH: The authors use Harrison et al.'s (2016) framework to explore the outcomes of a nine-month action research project whereby the authors observed the process and outcomes of implementing lean in a pharmacy intravenous admixture service of a Chinese hospital.

FINDINGS: The implementation of lean had positive results, which improved the efficiency of the operation, reduced the work start time and the amount of staff, and improved clinical satisfaction. In the process of implementation, nursing professionals showed a positive attitude toward the implementation and showed no obvious resistance under the positive influence of the head nurse. The combination of Chinese cultural characteristics, nursing culture and strong leadership enabled lean success.

ORIGINALITY/VALUE: The unit moved from self-management to a systemized process of using lean concepts and methods, it is an important change for hospital managers.}, } @article {pmid33631949, year = {2022}, author = {Davies, ST and Lloyd, CD and Polaschek, DLL}, title = {Does Reassessment Enhance the Prediction of Imminent Criminal Recidivism? Replicating Lloyd et al. (2020) With High-Risk Parolees.}, journal = {Assessment}, volume = {29}, number = {5}, pages = {962-980}, doi = {10.1177/1073191121993216}, pmid = {33631949}, issn = {1552-3489}, mesh = {*Criminals ; Humans ; Longitudinal Studies ; Male ; *Recidivism ; Risk Assessment/methods ; Risk Factors ; }, abstract = {Lloyd et al. (2020) proposed and tested a novel three-step framework for examining the extent to which reassessment of dynamic risk and protective factors enhances the prediction of imminent criminal recidivism. We conducted a conceptual replication of Lloyd et al.'s study. We used the same dynamic risk assessment measure in the same jurisdiction but, unlike Lloyd et al., our sample comprised solely high-risk men on parole in New Zealand (N = 966), the individuals who are most frequently reassessed in the community and most likely to imminently reoffend. The results of the previous study were largely reproduced: reassessment consistently enhanced prediction, with the most pronounced effects observed for a scale derived from theoretically acute dynamic risk factors. These findings indicate reassessment effects are robust to sample selection based on a narrower range of risk levels and remain robust across years of practice in applied contexts, despite potential organizational drift from initial training and reassessment fatigue. The findings also provide further support for the practice of ongoing risk reassessment in community supervision and suggest that the method proposed by Lloyd et al. is a replicable approach for testing the essential criteria for defining dynamic risk and protective factors.}, } @article {pmid33626211, year = {2021}, author = {Klimek, P and Convertino, AD and Pennesi, JL and Gonzales, M and Roesch, SC and Nagata, JM and Blashill, AJ}, title = {Confirmatory factor and measurement invariance analyses of the Eating Disorder Examination Questionnaire in sexual minority men and women.}, journal = {The International journal of eating disorders}, volume = {54}, number = {5}, pages = {745-754}, doi = {10.1002/eat.23488}, pmid = {33626211}, issn = {1098-108X}, support = {R25 GM058906/GM/NIGMS NIH HHS/United States ; }, mesh = {Adult ; *Feeding and Eating Disorders/diagnosis ; Female ; Gender Identity ; Humans ; Male ; Psychometrics ; Reproducibility of Results ; *Sexual and Gender Minorities ; Surveys and Questionnaires ; }, abstract = {OBJECTIVE: The present study aimed to investigate the factor structure of the Eating Disorder Examination Questionnaire (EDE-Q) in a large sample of cisgender sexual minority men and women, and subsequently, to evaluate measurement invariance by gender.

METHOD: The sample consisted of 962 sexual minority adult men (n = 479) and women (n = 483) who completed online self-report surveys. Confirmatory factor analysis was conducted using two previously supported factor structures (Friborg et al.'s four-factor model and Grilo et al.'s brief three-factor model) as well as the original four-factor structure of the EDE-Q.

RESULTS: Results indicated that the best fitting models were Friborg et al.'s four-factor model (CFI = .974, RMSEA = .098, SRMR = .0 70) and Grilo et al.'s brief three-factor model (CFI = .999, RMSEA = .049, SRMR = .017). The model fit of both factor structures were nearly identical when examined separately for men and women. The original four-factor structure could not be supported in this sample. Measurement invariance analyses further indicated that the best fitting models were invariant by gender in sexual minority individuals. Internal consistency was adequate for all subscales of Friborg et al.'s and Grilo et al.'s models.

DISCUSSION: The present study provides support for the use of the EDE-Q in sexual minority men and women. Additionally, findings demonstrate that the EDE-Q performs similarly in sexual minority men and women. Future research is needed to further evaluate measurement invariance of the EDE-Q by sexual orientation, gender identity, and race.}, } @article {pmid33625685, year = {2021}, author = {Caldwell, HAT and Scruton, S and Fierlbeck, K and Hajizadeh, M and Dave, S and Sim, SM and Kirk, SFL}, title = {Fare well to Nova Scotia? Public health investments remain chronically underfunded.}, journal = {Canadian journal of public health = Revue canadienne de sante publique}, volume = {112}, number = {2}, pages = {186-190}, pmid = {33625685}, issn = {1920-7476}, mesh = {Budgets/*trends ; COVID-19 ; Financing, Government/*economics ; Health Status Disparities ; Humans ; Noncommunicable Diseases/epidemiology ; Nova Scotia/epidemiology ; Public Health/*economics ; }, abstract = {Inspired by Fiset-Laniel et al.'s (2020) article entitled "Public health investments: neglect or wilful omission? Historical trends in Quebec and implications for Canada", we assessed public health investments since the establishment of the Nova Scotia provincial health authority in 2015. We analyzed Nova Scotia Department of Health and Wellness budgets from 2015-2016 to 2019-2020 and observed that less than 1% of funding was budgeted for public health annually, an amount well below the recommendation that 5-6% of healthcare funding be spent on public health. Healthcare spending has increased annually since 2015-2016, but proportions of funding to different programs and services have remained static. Specifically, we did not observe a change in investment in public health over time, suggesting that while the government does not necessarily spend too much or too little on healthcare, it spends far too little on public health. This chronic under-funding is problematic given the high rates of non-communicable diseases in Nova Scotia and health inequities experienced within the population. The 2020 COVID-19 pandemic has highlighted the importance of public health work, and the need for a pandemic recovery plan that prioritizes investment in all areas of public health in Nova Scotia.}, } @article {pmid33616529, year = {2021}, author = {Dweck, HK and Talross, GJ and Wang, W and Carlson, JR}, title = {Evolutionary shifts in taste coding in the fruit pest Drosophila suzukii.}, journal = {eLife}, volume = {10}, number = {}, pages = {}, pmid = {33616529}, issn = {2050-084X}, support = {R01 DC002174/DC/NIDCD NIH HHS/United States ; R01 DC004729/DC/NIDCD NIH HHS/United States ; R01 DC011697/DC/NIDCD NIH HHS/United States ; }, mesh = {Animals ; Biological Evolution ; Drosophila/genetics/*physiology ; Fragaria ; Fruit/chemistry ; Oviposition/*physiology ; Sensilla/physiology ; Species Specificity ; Taste/*genetics ; }, abstract = {Although most Drosophila species lay eggs in overripe fruit, the agricultural pest Drosophila suzukii lays eggs in ripe fruit. We found that changes in bitter taste perception have accompanied this adaptation. We show that bitter-sensing mutants of Drosophila melanogaster undergo a shift in egg laying preference toward ripe fruit. D. suzukii has lost 20% of the bitter-sensing sensilla from the labellum, the major taste organ of the head. Physiological responses to various bitter compounds are lost. Responses to strawberry purées are lost from two classes of taste sensilla. Egg laying is not deterred by bitter compounds that deter other species. Profiling of labellar transcriptomes reveals reduced expression of several bitter Gr genes (gustatory receptors). These findings support a model in which bitter compounds in early ripening stages deter egg laying in most Drosophila species, but a loss of bitter response contributes to the adaptation of D. suzukii to ripe fruit.}, } @article {pmid33614104, year = {2021}, author = {Wollast, R and Klein, O and VanLeeuwen, DM and Gervais, SJ and Bernard, P}, title = {Does Self-Objectification Entail an Opposition Between Appearance and Competence? The Likert Version of the Self-Objectification Questionnaire (LSOQ).}, journal = {Psychologica Belgica}, volume = {61}, number = {1}, pages = {33-45}, pmid = {33614104}, issn = {2054-670X}, abstract = {We propose a new method to test the reliability of Fredrickson et al.'s self-objectification questionnaire (SOQ). This scale being based on a ranking, traditional reliability estimates are inappropriate. Based on generalizability theory, we suggest to compute the reliability of each subset of questions related to physical appearance vs. physical competence separately in order to average them. We applied this method to a sample of female US undergraduates (n = 395) and evidenced that the reliability of the scale is very low (corrected Cronbach's alpha = .31). We also noted that a large proportion of the sample (32%) failed to complete the scale correctly. In a second study (n = 93), we propose a Likert adaptation of the scale and show that the two dimensions of the SOQ are independent. In Study 3 (n = 195), we confirm results of Study 2 and demonstrate that the general structure of the Likert version has satisfactory model fit statistics. These observations lead us to discourage the use of the original version of the SOQ and rely on the Likert version of the Self-Objectification Questionnaire (LSOQ, see appendix).}, } @article {pmid33603280, year = {2021}, author = {Renner, J and Neri, A and Puchinger, S}, title = {Low-rank parity-check codes over Galois rings.}, journal = {Designs, codes, and cryptography}, volume = {89}, number = {2}, pages = {351-386}, pmid = {33603280}, issn = {1573-7586}, abstract = {Low-rank parity-check (LRPC) codes are rank-metric codes over finite fields, which have been proposed by Gaborit et al. (Proceedings of the workshop on coding and cryptography WCC, vol 2013, 2013) for cryptographic applications. Inspired by a recent adaption of Gabidulin codes to certain finite rings by Kamche et al. (IEEE Trans Inf Theory 65(12):7718-7735, 2019), we define and study LRPC codes over Galois rings-a wide class of finite commutative rings. We give a decoding algorithm similar to Gaborit et al.'s decoder, based on simple linear-algebraic operations. We derive an upper bound on the failure probability of the decoder, which is significantly more involved than in the case of finite fields. The bound depends only on the rank of an error, i.e., is independent of its free rank. Further, we analyze the complexity of the decoder. We obtain that there is a class of LRPC codes over a Galois ring that can decode roughly the same number of errors as a Gabidulin code with the same code parameters, but faster than the currently best decoder for Gabidulin codes. However, the price that one needs to pay is a small failure probability, which we can bound from above.}, } @article {pmid33599286, year = {2021}, author = {Cheng, K and Lin, MH and Moreno, L and Skillman, J and Hickey, S and Cuenca, D and Hudlow, WR and Just, R and Bright, JA and Buckleton, J and Curran, JM}, title = {Modeling allelic analyte signals for aSTRs in NGS DNA profiles.}, journal = {Journal of forensic sciences}, volume = {66}, number = {4}, pages = {1234-1245}, doi = {10.1111/1556-4029.14685}, pmid = {33599286}, issn = {1556-4029}, support = {2020-DQ-BX-0022//NIJ/ ; HSHQDC-15-C-00064//Battelle National Biodefense Institute by the Department of Homeland Security Science and Technology Directorate (DHS S&T) for the management and operation of the National Biodefense Analysis and Countermeasures Center, a Federally Funded Research and Development Center/ ; }, mesh = {*Alleles ; DNA Fingerprinting/*methods ; *High-Throughput Nucleotide Sequencing ; Humans ; Likelihood Functions ; *Microsatellite Repeats ; Monte Carlo Method ; *Sequence Analysis, DNA ; }, abstract = {We describe an adaption of Bright et al.'s work modeling peak height variability in CE-DNA profiles to the modeling of allelic aSTR (autosomal short tandem repeats) read counts from NGS-DNA profiles, specifically for profiles generated from the ForenSeq™ DNA Signature Prep Kit, DNA Primer Mix B. Bright et al.'s model consists of three key components within the estimation of total allelic product-template, locus-specific amplification efficiencies, and degradation. In this work, we investigated the two mass parameters-template and locus-specific amplification efficiencies-and used MLE (maximum likelihood estimation) and MCMC (Markov chain Monte Carlo) methods to obtain point estimates to calculate the total allelic product. The expected read counts for alleles were then calculated after proportioning some of the expected stutter product from the total allelic product. Due to preferential amplicon selection introduced by the sample purification beads, degradation is difficult to model from the aSTR outputs alone. Improved modeling of the locus-specific amplification efficiencies may mask the effects of degradation. Whilst this model could be improved by introducing locus specific variances in addition to locus specific priors, our results demonstrate the suitability of adapting Bright et al.'s allele peak height model for NGS-DNA profiles. This model could be incorporated into continuous probabilistic interpretation approaches for mixed DNA profiles.}, } @article {pmid33598511, year = {2021}, author = {Jeong, DH and Jeong, W and Baeg, S and Kim, J}, title = {Datasets on the spatial distribution of mercury and its controlling factors in the Yellow Sea.}, journal = {Data in brief}, volume = {35}, number = {}, pages = {106792}, pmid = {33598511}, issn = {2352-3409}, abstract = {Large amount of anthropogenic mercury (Hg) emitted from China has been transported and deposited in the northwestern Pacific marginal seas; in particular, the Yellow Sea adjacent to China is immediately affected by Chinese-high Hg emissions [1,2]. This article presents the comprehensive baseline dataset on the mercury concentrations and their controlling factors in surface sediments from the entire Yellow Sea shelf, including Korean and Chinese rivers and coastal zones. These data supported the research article entitled "Sedimentary mercury (Hg) in the marginal seas adjacent to Chinese High-Hg emissions: source-to-sink, mass inventory, and accumulation history" Kim et al. [1]. Some of the data was used in Kim et al.'s research paper [3] with the reference [1]. A total of 492 surface sediments were collected from the Yellow Sea shelf and coastal zones, and the rivers around the Sea. All sediment samples were freeze-dried and ground by agate mortar for analyzing total mercury (THg) and related elemental components (total nitrogen, total carbon, total inorganic carbon, total organic carbon, and aluminum). Most previous studies on the sedimentary Hg were conducted locally, mainly in the river-dominated coastal and inner shelf zones of the Yellow Sea, which are associated with riverine Hg inputs. Thus, the quality and quantity of available sedimentary Hg data, on which we rely for mass inventories of Hg in the Sea, are limited. In this respect, our large dataset may contribute significantly to a better understanding of the behaviors of riverine and atmospheric Hg from Chinese sources and will help to further refine global estimates of Hg discharge to ocean margins and open oceans in East Asia. Additionally, the dataset will be essential for improving numerical model for global budget calculation and prediction.}, } @article {pmid33597917, year = {2021}, author = {Chen, Z and Tan, YJ and Lian, MM and Tandiono, M and Foo, JN and Lim, WK and Kandiah, N and Tan, EK and Ng, ASL}, title = {High Diagnostic Utility Incorporating a Targeted Neurodegeneration Gene Panel With MRI Brain Diagnostic Algorithms in Patients With Young-Onset Cognitive Impairment With Leukodystrophy.}, journal = {Frontiers in neurology}, volume = {12}, number = {}, pages = {631407}, pmid = {33597917}, issn = {1664-2295}, abstract = {Leukodystrophies are a diverse group of genetic disorders that selectively involve the white matter of the brain and are a frequent cause of young-onset cognitive impairment. Genetic diagnosis is challenging. Data on the utility of incorporating brain magnetic resonance imaging (MRI) diagnostic algorithms with next-generation sequencing (NGS) for diagnosis in a real-life clinical setting is limited. We performed sequencing using a custom-designed panel of 200 neurodegeneration-associated genes on 45 patients with young-onset cognitive impairment with leukodystrophy, and classified them based on van der Knaap et al.'s MRI diagnostic algorithm. We found that 20/45 (44.4%) patients carried pathogenic variants or novel variants predicted to be pathogenic (one in CSF1R, two in HTRA1 and 17 in NOTCH3). All patients with an established genetic diagnosis had an MRI brain pattern consistent with a specific genetic condition/s. More than half (19/37, 51.4%) of patients with MRI changes consistent with vascular cognitive impairment secondary to small vessel disease (VCI-SVD) had pathogenic variants, including all patients with pathogenic NOTCH3 (17/19, 89.5%) and HTRA1 variants (2/19, 11.5%). Amongst patients harboring pathogenic NOTCH3 variants, 13/17 (76.5%) carried the p.R544C variant seen predominantly in East Asians. Anterior temporal white matter involvement was seen only in patients with pathogenic NOTCH3 variants (6/17, 35.3%). Overall, we demonstrated a high diagnostic utility incorporating a targeted neurodegeneration gene panel and MRI-based diagnostic algorithms in young-onset cognitive impairment patients with leukodystrophy.}, } @article {pmid33594534, year = {2022}, author = {Mrdjenovich, AJ}, title = {Fishing in a Puddle of Doubt and Disbelief?: A Rejoinder to the Speed et al. Commentary.}, journal = {Journal of religion and health}, volume = {61}, number = {3}, pages = {2323-2330}, pmid = {33594534}, issn = {1573-6571}, mesh = {Humans ; Emotions ; Health Status ; *Religion ; Surveys and Questionnaires ; }, abstract = {In the article "Religiously/Spiritually Involved, but in Doubt or Disbelief-Why? Healthy?", Mrdjenovich (in J Relig Health https://doi.org/10.1007/s10943-018-0711-2 , 2018) explored the practices of religious attendance and prayer among atheists and agnostic theists. Speed et al. (in J Relig Health https://doi.org/10.1007/s10943-020-01109-1 , 2020) offered a commentary regarding Mrdjenovich's (2018) article with attention to moderators of associations between religious/spiritual constructs and health outcomes. In this rejoinder, I review Speed et al.'s (2020) commentary and I identify a number of concerns, both with their observations and ostensive oversights involving qualitative research methodology, the utility of survey data, the domain of belief, and the impact of calls for a pluralistic approach in the religion-heath research field. I conclude that Mrdjenovich does not misunderstand mechanisms of the (non)religion-health relationship as much as Speed et al. seem to misinterpret Mrdjenovich's (2018) purpose, perspective, and default position on the issues. I reiterate that a concerted effort is required to study health outcomes among religious minorities.}, } @article {pmid33593174, year = {2021}, author = {Harris, EA and Van Bavel, JJ}, title = {Preregistered Replication of "Feeling Superior Is a Bipartisan Issue: Extremity (Not Direction) of Political Views Predicts Perceived Belief Superiority".}, journal = {Psychological science}, volume = {32}, number = {3}, pages = {451-458}, doi = {10.1177/0956797620968792}, pmid = {33593174}, issn = {1467-9280}, mesh = {*Attitude ; Emotions ; Extremities ; Humans ; *Politics ; Prejudice ; }, abstract = {There is currently a debate in political psychology about whether dogmatism and belief superiority are symmetric or asymmetric across the ideological spectrum. Toner, Leary, Asher, and Jongman-Sereno (2013) found that dogmatism was higher among conservatives than liberals, but both conservatives and liberals with extreme attitudes reported higher perceived superiority of beliefs. In the current study, we conducted a preregistered direct and conceptual replication of this previous research using a large nationally representative sample. Consistent with Toner et al.'s findings, our results showed that conservatives had higher dogmatism scores than liberals, whereas both conservative and liberal extreme attitudes were associated with higher belief superiority compared with more moderate attitudes. As in their study, we also found that whether conservative or liberal attitudes were associated with higher belief superiority was topic dependent. Contrasting Toner et al.'s findings, our results also showed that ideologically extreme individuals had higher dogmatism. We discuss implications of these results for theoretical debates in political psychology.}, } @article {pmid33578128, year = {2021}, author = {Quintana-Sosa, M and León-Mejía, G and Luna-Carrascal, J and De Moya, YS and Rodríguez, IL and Acosta-Hoyos, A and Anaya-Romero, M and Trindade, C and Narváez, DM and Restrepo, HG and Dias, J and Niekraszewicz, L and Garcia, ALH and Rohr, P and da Silva, J and Henriques, JAP}, title = {Cytokinesis-block micronucleus cytome (CBMN-CYT) assay biomarkers and telomere length analysis in relation to inorganic elements in individuals exposed to welding fumes.}, journal = {Ecotoxicology and environmental safety}, volume = {212}, number = {}, pages = {111935}, doi = {10.1016/j.ecoenv.2021.111935}, pmid = {33578128}, issn = {1090-2414}, mesh = {Air Pollutants, Occupational/*analysis ; *Biological Assay ; Biomarkers/analysis ; Cytokinesis ; DNA Damage ; Humans ; Lymphocytes ; Micronucleus Tests/*methods ; Occupational Exposure/*analysis ; Oxidative Stress ; *Telomere ; Welding ; }, abstract = {During the welding activities many compounds are released, several of these cause oxidative stress and inflammation and some are considered carcinogenic, in fact the International Agency for Research on Cancer established that welding fumes are carcinogenic to humans. The aim of the present study was to analyze the cytotoxic and genotoxic potential of exposure to welding fumes and to determine concentrations of metals in blood and urine of occupationally exposed workers. We included 98 welders and 100 non-exposed individuals. Our results show significant increase in the frequency of micronuclei (MN), nucleoplasmic bridges (NPB), nuclear buds (NBUD) and necrotic cells (NECR) in cytokinesis-block micronucleus cytome (CBMN-Cyt) assay, as well as in the telomere length (TL) of the exposed individuals with respect to the non-exposed group. In the analysis of the concentrations of inorganic elements using PIXE method, were found higher concentrations of Cr, Fe and Cu in the urine, and Cr, Fe, Mg, Al, S, and Mn in the blood in the exposed group compared to the non-exposed group. A significant correlation was observed between MN and age and between NPB and years of exposure. Additionally, we found a significant correlation for TL in relation to MN, NPB, age and years of exposure in the exposed group. Interestingly, a significant correlation between MN and the increase in the concentration of Mg, S, Fe and Cu in blood samples of the exposed group, and between MN and Cr, Fe, Ni and Cu in urine. Thus, our findings may be associated with oxidative and inflammatory damage processes generated by the components contained in welding fumes, suggesting a high occupational risk in welding workers.}, } @article {pmid33573308, year = {2021}, author = {Kwon, DK and Yu, SJ and Lee, JY and Son, SH and Park, YH}, title = {WSN-SLAP: Secure and Lightweight Mutual Authentication Protocol for Wireless Sensor Networks.}, journal = {Sensors (Basel, Switzerland)}, volume = {21}, number = {3}, pages = {}, pmid = {33573308}, issn = {1424-8220}, mesh = {*Computer Security ; Computer Simulation ; *Confidentiality ; Logic ; }, abstract = {Wireless sensor networks (WSN) are widely used to provide users with convenient services such as health-care, and smart home. To provide convenient services, sensor nodes in WSN environments collect and send the sensing data to the gateway. However, it can suffer from serious security issues because susceptible messages are exchanged through an insecure channel. Therefore, secure authentication protocols are necessary to prevent security flaws in WSN. In 2020, Moghadam et al. suggested an efficient authentication and key agreement scheme in WSN. Unfortunately, we discover that Moghadam et al.'s scheme cannot prevent insider and session-specific random number leakage attacks. We also prove that Moghadam et al.'s scheme does not ensure perfect forward secrecy. To prevent security vulnerabilities of Moghadam et al.'s scheme, we propose a secure and lightweight mutual authentication protocol for WSNs (WSN-SLAP). WSN-SLAP has the resistance from various security drawbacks, and provides perfect forward secrecy and mutual authentication. We prove the security of WSN-SLAP by using Burrows-Abadi-Needham (BAN) logic, Real-or-Random (ROR) model, and Automated Verification of Internet Security Protocols and Applications (AVISPA) simulation. In addition, we evaluate the performance of WSN-SLAP compared with existing related protocols. We demonstrate that WSN-SLAP is more secure and suitable than previous protocols for WSN environments.}, } @article {pmid33565321, year = {2022}, author = {Stonbraker, S and Flynn, G and George, M and Cunto-Amesty, S and Alcántara, C and Abraído-Lanza, AF and Halpern, M and Rowell-Cunsolo, T and Bakken, S and Schnall, R}, title = {Feasibility and acceptability of using information visualizations to improve HIV-related communication in a limited-resource setting: a short report.}, journal = {AIDS care}, volume = {34}, number = {4}, pages = {535-541}, pmid = {33565321}, issn = {1360-0451}, support = {K24 NR018621/NR/NINR NIH HHS/United States ; K99 NR017829/NR/NINR NIH HHS/United States ; R00 NR017829/NR/NINR NIH HHS/United States ; }, mesh = {Humans ; Communication ; Feasibility Studies ; *HIV Infections ; *Physicians ; }, abstract = {Infographics (visualizations that present information) can assist clinicians to offer health information to patients with low health literacy in an accessible format. In response, we developed an infographic intervention to enhance clinical, HIV-related communication. This study reports on its feasibility and acceptability at a clinical setting in the Dominican Republic. We conducted in-depth interviews with physicians who administered the intervention and patients who received it. We conducted audio-recorded interviews in Spanish using semi-structured interview guides. Recordings were professionally transcribed verbatim then analyzed using descriptive content analysis. Physician transcripts were deductively coded according to constructs of Bowen et al.'s feasibility framework and patient transcripts were inductively coded. Three physicians and 26 patients participated. Feasibility constructs endorsed by physicians indicated that infographics were easy to use, improved teaching, and could easily be incorporated into their workflow. Coding of patient transcripts identified four categories that indicated the intervention was acceptable and useful, offered feedback regarding effective clinical communication, and recommended improvements to infographics. Taken together, these data indicate our intervention was a feasible and acceptable way to provide clinical, HIV-related information and provide important recommendations for future visualization design as well as effective clinical communication with similar patient populations.}, } @article {pmid33564968, year = {2021}, author = {Bermudez-Contreras, E}, title = {Deep reinforcement learning to study spatial navigation, learning and memory in artificial and biological agents.}, journal = {Biological cybernetics}, volume = {115}, number = {2}, pages = {131-134}, pmid = {33564968}, issn = {1432-0770}, mesh = {Artificial Intelligence ; Biological Factors ; Neural Networks, Computer ; Reinforcement, Psychology ; *Spatial Navigation ; }, abstract = {Despite the recent advancements and popularity of deep learning that has resulted from the advent of numerous industrial applications, artificial neural networks (ANNs) still lack crucial features from their biological counterparts that could improve their performance and their potential to advance our understanding of how the brain works. One avenue that has been proposed to change this is to strengthen the interaction between artificial intelligence (AI) research and neuroscience. Since their historical beginnings, ANNs and AI, in general, have developed in close alignment with both neuroscience and psychology. In addition to deep learning, reinforcement learning (RL) is another approach that is strongly linked to AI and neuroscience to understand how learning is implemented in the brain. In a recently published article, Botvinick et al. (Neuron, 107:603-616, 2020) explain why deep reinforcement learning (DRL) is important for neuroscience as a framework to study learning, representations and decision making. Here, I summarise Botvinick et al.'s main arguments and frame them in the context of the study of learning, memory and spatial navigation. I believe that applying this approach to study spatial navigation can provide useful insights for the understanding of how the brain builds, processes and stores representations of the outside world to extract knowledge.}, } @article {pmid33560978, year = {2021}, author = {Altenhofen, C and Ewald, T and Stork, A and Fellner, DW}, title = {Analyzing and Improving the Parameterization Quality of Catmull-Clark Solids for Isogeometric Analysis.}, journal = {IEEE computer graphics and applications}, volume = {41}, number = {3}, pages = {34-47}, doi = {10.1109/MCG.2021.3057905}, pmid = {33560978}, issn = {1558-1756}, abstract = {In the field of physically based simulation, high quality of the simulation model is crucial for the correctness of the simulation results and the performance of the simulation algorithm. When working with spline or subdivision models in the context of isogeometric analysis, the quality of the parameterization has to be considered in addition to the geometric quality of the control mesh. Following Cohen et al.'s concept of model quality in addition to mesh quality, we present a parameterization quality metric tailored for Catmull-Clark (CC) solids. It measures the quality of the limit volume based on a quality measure for conformal mappings, revealing local distortions and singularities. We present topological operations that resolve these singularities by splitting certain types of boundary cells that typically occur in interactively designed CC-solid models. The improved models provide higher parameterization quality that positively affects the simulation results without additional computational costs for the solver.}, } @article {pmid33554368, year = {2022}, author = {Sosa-Soto, J and Padrón-Covarrubias, AI and Márquez-Preciado, R and Ruiz-Rodríguez, S and Pozos-Guillén, A and Pedroza-Uribe, IM and Bayardo-González, RA and Garrocho-Rangel, A}, title = {Molar incisor hypomineralization (MIH): prevalence and degree of severity in a Mexican pediatric population living in an endemic fluorosis area.}, journal = {Journal of public health dentistry}, volume = {82}, number = {1}, pages = {3-10}, doi = {10.1111/jphd.12446}, pmid = {33554368}, issn = {1752-7325}, mesh = {Child ; *Dental Enamel Hypoplasia/epidemiology ; *Fluorosis, Dental/epidemiology ; Humans ; Incisor ; Molar ; Prevalence ; }, abstract = {OBJECTIVE: To estimate the prevalence and severity of molar incisor hypomineralization (MIH) in 8 years old children living in an endemic fluorosis area.

METHODS: MIH prevalence rate was determined from a study sample comprising 613 participants. They were recruited from 11 urban public schools with similar socio-economic status. Oral evaluations were performed and diagnosed MIH teeth were classified under Ghanim et al.'s criteria. Statistical descriptive and comparative analyzes were carried out.

RESULTS: First permanent molars were the tooth group most affected, followed by the upper central incisors, lower central incisors, lower lateral incisors, and upper lateral incisors. There was no significant statistical difference by gender and by maxillary/mandible arches (P = 0.82 and 0.26, respectively). The frequency of MIH was more in molars compared to incisors (P < 0.02).

CONCLUSIONS: The MIH prevalence in this study was 12.4 percent. According to the MIH severity, degree 2 was the most frequently detected (76.4 percent).}, } @article {pmid33543709, year = {2021}, author = {Ashcroft, P and Lehtinen, S and Angst, DC and Low, N and Bonhoeffer, S}, title = {Quantifying the impact of quarantine duration on COVID-19 transmission.}, journal = {eLife}, volume = {10}, number = {}, pages = {}, pmid = {33543709}, issn = {2050-084X}, support = {EpiPose,101003688//H2020 European Research Council/ ; EpiPose 101003688//H2020 European Research Council/ ; 176233/SNSF_/Swiss National Science Foundation/Switzerland ; 176401/SNSF_/Swiss National Science Foundation/Switzerland ; }, mesh = {COVID-19/*epidemiology/*transmission/virology ; Contact Tracing ; Humans ; *Models, Theoretical ; Pandemics ; Public Health Surveillance ; *Quarantine ; *SARS-CoV-2/physiology ; Time Factors ; }, abstract = {The large number of individuals placed into quarantine because of possible severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) exposure has high societal and economic costs. There is ongoing debate about the appropriate duration of quarantine, particularly since the fraction of individuals who eventually test positive is perceived as being low. We use empirically determined distributions of incubation period, infectivity, and generation time to quantify how the duration of quarantine affects onward transmission from traced contacts of confirmed SARS-CoV-2 cases and from returning travellers. We also consider the roles of testing followed by release if negative (test-and-release), reinforced hygiene, adherence, and symptoms in calculating quarantine efficacy. We show that there are quarantine strategies based on a test-and-release protocol that, from an epidemiological viewpoint, perform almost as well as a 10-day quarantine, but with fewer person-days spent in quarantine. The findings apply to both travellers and contacts, but the specifics depend on the context.}, } @article {pmid33542839, year = {2021}, author = {De Luna, V and De Maio, F and Caterini, A and Marsiolo, M and Petrungaro, L and Ippolito, E and Farsetti, P}, title = {Surgical Treatment of Severe Idiopathic Flexible Flatfoot by Evans-Mosca Technique in Adolescent Patients: A Long-Term Follow-Up Study.}, journal = {Advances in orthopedics}, volume = {2021}, number = {}, pages = {8843091}, pmid = {33542839}, issn = {2090-3464}, abstract = {Flexible idiopathic flatfoot is very common in growing age and rarely causes pain or disability. Surgery is indicated only in severe symptomatic cases that are resistant to conservative treatment, and numerous surgical procedures have been proposed. Lateral column calcaneal lengthening as described by Evans and modified by Mosca is a widely used surgical technique for the correction of severe symptomatic flexible flatfoot. In the present study, we report the long-term clinical and radiographic results in 14 adolescent patients (mean age: 12.8 years) affected by severe symptomatic flexible flatfoot, surgically treated by Evans-Mosca procedure, for a total of 26 treated feet (12 cases bilateral and 2 unilateral). In all cases, surgery was indicated for the presence of significant symptoms resistant to nonsurgical management. Clinical evaluation was made according to the American Orthopedic Foot and Ankle Society (AOFAS) Ankle-Hindfoot Scale, the Foot and Ankle Disability Index (FADI) Score, and Yoo et al.'s criteria. Radiographic evaluation was made using anteroposterior and lateral weight-bearing radiographs of the feet to evaluate Meary's angle and Costa-Bertani's angle and to evaluate possible osteoarthritic changes in the midtarsal joints. At follow-up (mean: 7 years and 7 months), we observed a satisfactory result in all patients. The mean average score of the AOFAS Ankle-Hindfoot Scale improved from 60.03 points to 95.26; the mean FADI score improved from 71.41 to 97.44; and according to Yoo et al.'s criteria, the average clinical outcome score was 10.96. At radiographic examination, nonunion of the calcaneal osteotomy was never observed. Meary's angle improved from an average preoperative value of 25° to 1.38° at follow-up; Costa-Bertani's angle improved from an average preoperative value of 154.2° to 130.9° at follow-up. In no case, significant radiographic signs of midtarsal joint arthritis were observed. According to our results, we believe that Evans-Mosca technique is a valid option of surgical treatment for severe idiopathic flexible flatfoot and allows a satisfactory correction of the deformity with a low rate of complications.}, } @article {pmid33533286, year = {2023}, author = {Zarshenas, S and Gagnon-Roy, M and Couture, M and Bier, N and Giroux, S and Nalder, E and Pigot, H and Dawson, D and Poncet, F and LeDorze, G and Bottari, C and , }, title = {Potential of using an assistive technology to address meal preparation difficulties following acquired brain injury: clients' and caregivers' perspectives.}, journal = {Disability and rehabilitation. Assistive technology}, volume = {18}, number = {4}, pages = {458-466}, doi = {10.1080/17483107.2020.1867244}, pmid = {33533286}, issn = {1748-3115}, support = {TBI 144225//CIHR/Canada ; }, mesh = {Adult ; Humans ; Caregivers/psychology ; Adaptation, Psychological ; *Brain Injuries ; *Self-Help Devices ; Ontario ; }, abstract = {OBJECTIVES: This study explored difficulties in meal preparation experienced by adults with moderate to severe acquired brain injury (ABI) and available compensatory strategies from both ABI individuals' and caregivers' perspectives. Further, this study investigated their opinions on potential benefits, barriers and facilitators to the use of the Cognitive Orthosis for coOKing (COOK) in their living environment.

METHODS: Using a qualitative descriptive approach, semi-structured individual interviews and focus groups were carried out with adults with moderate to severe ABI (n = 20) and formal and informal caregivers (n = 13) in Ontario and Quebec, Canada. A qualitative analysis based on Miles et al.'s approach was used.

RESULTS: According to participants, cognitive, physical, psychosocial dysfunctions and lack of availability of supportive caregivers were the main difficulties that impede persons with ABI from engaging effectively in meal preparation tasks. Memory aids on smartphones, and caregivers' direct support were reported as the most commonly used compensatory strategies, though the latter do not provide adequate support. COOK was identified as a technology with great potential to improve independence and increase safety in meal preparation for these clients while decreasing caregiver burden. However, psychosocial issues and limited access to funding were considered as the main barriers to the use of COOK. Providing training and the availability of financial support were mentioned as the main facilitators to the use of this technology.

CONCLUSIONS: Findings of this study on difficulties of meal preparation following ABI and potential benefits and barriers of COOK will help improve this technology and customize it to the needs of clients with ABI and their caregivers.Implications for RehabilitationCurrent compensatory strategies are not tailored to the specific needs of clients with ABI and cannot provide sufficient support for caregivers.COOK shows a high potential for increasing independence and safety during meal preparation in a living environment for clients with ABI via a sensor-based autonomous safety system and a cognitive assistance application.COOK has the potential to decrease caregivers' burden by proving remote access to a stove/oven.}, } @article {pmid33530964, year = {2021}, author = {Emamian, MH and Ebrahimi, H and Hashemi, H and Fotouhi, A}, title = {Salt intake and blood pressure in Iranian children and adolescents: a population-based study.}, journal = {BMC cardiovascular disorders}, volume = {21}, number = {1}, pages = {62}, pmid = {33530964}, issn = {1471-2261}, mesh = {Adolescent ; Age Factors ; *Blood Pressure ; Body Mass Index ; Child ; Diet, Sodium-Restricted ; Female ; Humans ; Hypertension/diagnosis/epidemiology/*physiopathology/prevention & control ; Iran/epidemiology ; Male ; Prevalence ; Recommended Dietary Allowances ; Risk Assessment ; Risk Factors ; Rural Health ; Sex Factors ; Sodium, Dietary/*adverse effects/urine ; Urban Health ; }, abstract = {BACKGROUND: Previous studies have reported a high prevalence of hypertension in Iranian students, especially in rural areas. The aim of this study was to investigate the daily intake of salt in students and its association with high blood pressure.

METHODS: A random sub-sample was selected from the participants of the second phase of Shahroud schoolchildren eye cohort study and then a random urine sample was tested for sodium, potassium and creatinine. Urine electrolyte esexcretion and daily salt intake were calculated by Tanaka et al.'s formula.

RESULTS: Among 1455 participants (including 230 participants from rural area and 472 girls), the mean age was 12.9 ± 1.7 year and the mean daily salt intake was 9.7 ± 2.6 g (95% CI 9.5-9.8). The mean salt consumption in rural areas [10.8 (95% CI 10.4-11.2)] was higher than urban areas [9.4 (95% CI 9.3-9.6)], in people with hypertension [10.8 (95% CI 10.3-11.3)] was more than people with normal blood pressure [9.4 (95% CI 9.3-9.6)], and in boys [9.8 (95% CI 9.7-10.0)] was more than girls [9.3 (95% CI 9.1-9.6)]. Higher age, BMI z-score, male sex and rural life, were associated with increased daily salt intake. Increased salt intake was associated with increased systolic and diastolic blood pressure.

CONCLUSION: Daily salt intake in Iranian adolescents was about 2 times the recommended amount of the World Health Organization, was higher in rural areas and was associated with blood pressure. Reducing salt intake should be considered as an important intervention, especially in rural areas.}, } @article {pmid33528820, year = {2021}, author = {Cornel, T}, title = {Contested Numbers: The failed negotiation of objective statistics in a methodological review of Kinsey et al.'s sex research.}, journal = {History and philosophy of the life sciences}, volume = {43}, number = {1}, pages = {13}, pmid = {33528820}, issn = {1742-6316}, mesh = {Biomedical Research/*history ; Biostatistics/*history/methods ; History, 20th Century ; Humans ; Psychiatry/*history ; *Sexual Behavior ; }, abstract = {From 1950 to 1952, statisticians W.G. Cochran, C.F. Mosteller, and J.W. Tukey reviewed A.C. Kinsey and colleagues' methodology. Neither the history-and-philosophy of science literature nor contemporary theories of interdisciplinarity seem to offer a conceptual model that fits this forced interaction, which was characterized by significant power asymmetries and disagreements on multiple levels. The statisticians initially attempted to exclude all non-technical matters from their evaluation, but their political and personal investments interfered with this agenda. In the face of McCarthy's witch hunts, negotiations with Kinsey and his funding institutions became integral to the review group's work. This paper analyzes the heavy burden of emotional and affective labor in this collaboration, the conflicts caused by competing visions of objectivity, and the uses of statistical knowledge to gain and sustain authority. Kinsey's refusal to adopt the recommended probability sample damaged his already precarious position even further and marked him as a biased researcher who put his personal agenda above methodological rigor. Kinsey's uncooperative demeanor can be explained by distrust resulting from numerous adverse reactions to his work and by fear of having his sexuality exposed. This case study illustrates that the very concept of valid numbers can become an arena for power struggles and that quantification alone does not guarantee productive exchanges across disciplines. It calls for a deeper conceptual analysis of the prerequisites for successful scientific collaborations.}, } @article {pmid33522337, year = {2022}, author = {Linning, SJ and Silver, IA and Papp, J}, title = {Exploring the Correspondence Between General Correctional Programming and Inmate Misconduct Using a Time-Course Framework.}, journal = {International journal of offender therapy and comparative criminology}, volume = {66}, number = {2-3}, pages = {209-226}, pmid = {33522337}, issn = {1552-6933}, mesh = {Humans ; Ohio ; *Prisoners ; Prisons ; *Problem Behavior ; }, abstract = {Inmate misconduct continues to threaten safety and order within correctional institutions. Yet few studies have examined its longitudinal nature. In this paper we explore the correspondence between correctional programming and inmate misconduct. To do this, we draw from Linning et al.'s time-course framework devised to improve the design and evaluation of interventions by considering effects that can occur before, during, and after programming. We provide the first empirical demonstration of their framework using prisoner misconduct data collected from all Ohio prisons between January 2008 and June 2012. A cross-lagged panel analysis provides support for the use of a time-course framework. Results show that misconduct decreased during programming. However, we observed increases in misconduct prior to and following exposure to programming. Our results suggest that future work needs to improve our understanding of causal mechanisms of inmate misconduct and when their effects are expected.}, } @article {pmid33521148, year = {2021}, author = {Najafi, F and Nikbakht Nasrabadi, A and Mardanian Dehkordi, L}, title = {Exploring the Lived Experience of Missed Nursing Care in Postgraduate Nursing Students in Iran.}, journal = {International journal of community based nursing and midwifery}, volume = {9}, number = {1}, pages = {44-54}, pmid = {33521148}, issn = {2322-2476}, abstract = {BACKGROUND: Missed care is a global phenomenon, which can include many clinical conditions that threaten the patients' safety in all countries and cultures, and also indicates the quality of nursing care. The nursing students' awareness and understanding of missed nursing care is of great importance. The current study aims to explore the lived experience of postgraduate nursing students in missed care.

METHODS: The current qualitative study was performed based on the interpretive phenomenological approach in Tehran, Iran, in February to December 2019. A total of 10 master's degree nursing students were selected through purposive sampling. A total of 10 semi-structured individual interviews were used to collect the data. The trail version of MAXQDA-10 software was used for coding. All interviews were recorded and codified, and the main themes were extracted from them using Dicklemann et al.'s (1989) analytical method.

RESULTS: Two main themes, five sub-themes, and 31 meaning units were obtained. The main themes included: "unfulfilled care" and "living in limbo".

CONCLUSION: Missed care, as unfulfilled care, is accompanied with living in limbo for nursing students, and this condition is influenced by organizational and personal factors. It seems that managers can prevent missed nursing care by supervising nursing care, reducing the nurses' workload, creating a sense of commitment to work, and enforcing ethical issues among nurses.}, } @article {pmid33485333, year = {2021}, author = {Westergren, T and Mølland, E and Haraldstad, K and Tellefsen Håland, Å and Stamnes Köpp, UM and Fegran, L and Abildsnes, E}, title = {Implementation of the norwegian 'Starting right' child health service innovation: implementation adjustments, adoption, and acceptability.}, journal = {BMC health services research}, volume = {21}, number = {1}, pages = {86}, pmid = {33485333}, issn = {1472-6963}, support = {285009//Regional Research Fund in Agder/ ; }, mesh = {Child ; *Child Health Services ; Child, Preschool ; Female ; Humans ; Norway ; Parents ; School Health Services ; Surveys and Questionnaires ; }, abstract = {BACKGROUND: An increased and/or stable proportion of the child and adolescent population reports symptoms of impaired health, and the symptoms can be identified early. Therefore, structured child- and parent-reported outcome measures need to be implemented in child and school health services for decision support and identification of children at risk. We aimed to (a) qualitatively examine adjustments of active implementation from the pilot implementation of the Norwegian 'Starting Right' health service innovation including an online child health assessment tool and practical routines, and (b) measure practitioners´ adoption and parental acceptability.

METHODS: We used a mixed-methods design to qualitatively examine adjustments from working notes and meeting memoranda, and quantitatively assess adoption and acceptability from user rates provided by the systems log. Twenty-one child and school health nurses (CSHNs) from two child health centers participated in the implementation pilot of online health assessments in children aged 2-, 4- and 6-year. We used a deductive and narrative analysis approach using Fixsen et al.´s core implementation components to code and sort adjustments.

RESULTS: Core implementation components were adjusted throughout the pilot implementation. Researchers´ increased their availability in reciprocity with staff evaluation to integrate active implementation adjustments. We launched a project for improved data systems integration. The overall CSHNs adoption rate was satisfactory and higher in center A, where a medical secretary supported the nurses through the entire pilot phase, than in center B (96 vs. 55 %). Parental acceptability rate was overall high (77 %) with increased rates among parents of 6-year-old children (98 %) compared with younger ones (78-85 %), and in cases where both parents received the questionnaires.

CONCLUSIONS: The 'Starting Right' health service innovation implementation was actively adjusted by integration of core implementation components mainly based on staff evaluation. The CSHNs adopted the innovation which was also acceptable to parents.}, } @article {pmid33484225, year = {2021}, author = {Feingold, JH and Drossman, DA}, title = {Deconstructing stigma as a barrier to treating DGBI: Lessons for clinicians.}, journal = {Neurogastroenterology and motility}, volume = {33}, number = {2}, pages = {e14080}, pmid = {33484225}, issn = {1365-2982}, support = {TL1 TR001434/TR/NCATS NIH HHS/United States ; }, mesh = {*Gastrointestinal Diseases/therapy ; Humans ; *Social Stigma ; }, abstract = {Stigma, defined as social devaluation based on negative stereotypes toward a particular population, is prevalent within health care and is a common phenomenon in disorders of gut-brain interaction (DGBI). Characteristically, DGBI including functional dyspepsia (FD) lack a structural etiology to explain symptoms, have high psychiatric co-morbidity, and respond to neuromodulators traditionally used to treat psychopathology. As a result, these disorders are frequently and wrongly presumed to be psychiatric and carry a great deal of stigma. Stigma has profound adverse consequences for patients, including emotional distress, medication non-adherence, barriers to accessing care, and increased symptoms. The basis for stigma dates back to the 17th Century concept of mind-body dualism. Patients and health care providers need to understand the factors that promote stigma and methods to ameliorate it. In this minireview, we address the data presented in Yan et al.'s (Neurogastroenterol Motil, 2020, e13956). We offer concrete solutions for clinicians to mitigate the impact of stigma to optimize treatment adherence and clinical outcomes for patients with DGBI.}, } @article {pmid33479811, year = {2021}, author = {Wong, J and Kallish, N and Crown, D and Capraro, P and Trierweiler, R and Wafford, QE and Tiema-Benson, L and Hassan, S and Engel, E and Tamayo, C and Heinemann, AW}, title = {Job Accommodations, Return to Work and Job Retention of People with Physical Disabilities: A Systematic Review.}, journal = {Journal of occupational rehabilitation}, volume = {31}, number = {3}, pages = {474-490}, pmid = {33479811}, issn = {1573-3688}, support = {90RTEM0001/ACL/ACL HHS/United States ; 90RTEM0001/ACL/ACL HHS/United States ; }, mesh = {Cross-Sectional Studies ; *Persons with Disabilities ; Employment ; Humans ; *Return to Work ; Workplace ; }, abstract = {Purpose We aimed to identify job accommodations that help persons with physical disabilities maintain or return to work and explore the barriers and facilitators that influence the provision and reception of job accommodations. Methods We conducted a systematic review using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The review was registered in PROSPERO (CRD42019129645). The search strategy incorporated keywords describing physical disabilities, employer-approved job accommodations, and employment retention or return to work approaches. We searched MEDLINE, the Cochrane Library, Embase, CINAHL, PsycINFO, Web of Science, and ProQuest Theses and dissertations. Reviewers independently selected studies for inclusion. We used Hawker et al.'s method to assess study quality. Results We identified 2203 articles, of which 52 met inclusion criteria, developed a table of job accommodations commonly used by persons with physical disabilities, summarized the percentages of job accommodations used by persons with disabilities, synthesized evidence of the effectiveness of job accommodations, and identified the factors that influence job accommodation use. The most frequently reported accommodations were as follows: modification of job responsibilities, change of workplace policy, supportive personnel provision, flexible scheduling, and assistive technology. We summarized four types of facilitators and barriers that affect job accommodation use: employee-related factors, accommodation-related factors, job-related factors, and social workplace-related factors. Conclusion The absence of randomized controlled trials and prevalence of cross-sectional surveys provides inconclusive evidence regarding the effectiveness of specific job accommodations for people with particular functional limitations. Our system of categorizing job accommodations provides a guide to investigators seeking to evaluate the effectiveness of job accommodations using experimental methods.}, } @article {pmid33472636, year = {2021}, author = {Vilar-Compte, M and Burrola-Méndez, S and Lozano-Marrufo, A and Ferré-Eguiluz, I and Flores, D and Gaitán-Rossi, P and Teruel, G and Pérez-Escamilla, R}, title = {Urban poverty and nutrition challenges associated with accessibility to a healthy diet: a global systematic literature review.}, journal = {International journal for equity in health}, volume = {20}, number = {1}, pages = {40}, pmid = {33472636}, issn = {1475-9276}, support = {UL1 TR001863/TR/NCATS NIH HHS/United States ; }, mesh = {*Diet, Healthy/economics/statistics & numerical data ; *Global Health/statistics & numerical data ; Humans ; *Nutritional Status ; *Poverty/statistics & numerical data ; Social Determinants of Health ; *Urban Population/statistics & numerical data ; }, abstract = {BACKGROUND: There is an increasing global trend towards urbanization. In general, there are less food access issues in urban than rural areas, but this "urban advantage" does not benefit the poorest who face disproportionate barriers to accessing healthy food and have an increased risk of malnutrition.

OBJECTIVES: This systematic literature review aimed to assess urban poverty as a determinant of access to a healthy diet, and to examine the contribution of urban poverty to the nutritional status of individuals.

METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) methodology, our review included quantitative and qualitative studies published in English or in Spanish between 2000 and 2019. The articles were eligible if they focused on nutrition access (i.e. access to a healthy diet) or nutrition outcomes (i.e., anemia, overweight and obesity, micronutrient deficiency, micronutrient malnutrition) among urban poor populations. Articles were excluded if they did not meet pre-established criteria. The quality of the quantitative studies was assessed by applying Khan et al.'s methodology. Similarly, we assessed the quality of qualitative articles through an adapted version of the National Institute for Health and Care Excellence (NICE) methodology checklist. Finally, we systematically analyzed all papers that met the inclusion criteria based on a qualitative content and thematic analysis.

RESULTS: Of the 68 papers included in the systematic review, 55 used quantitative and 13 used qualitative methods. Through the analysis of the literature we found four key themes: (i) elements that affect access to healthy eating in individuals in urban poverty, (ii) food insecurity and urban poverty, (iii) risk factors for the nutritional status of urban poor and (iv) coping strategies to limited access to food. Based on the systematization of the literature on these themes, we then proposed a conceptual framework of urban poverty and nutrition.

CONCLUSIONS: This systematic review identified distinct barriers posed by urban poverty in accessing healthy diets and its association with poorer nutrition outcomes, hence, questioning the "urban advantage". A conceptual framework emerging from the existing literature is proposed to guide future studies and policies.

PROSPERO Registration number: CRD42018089788 .}, } @article {pmid33471250, year = {2021}, author = {Farrington, JW}, title = {Reflections about three influential Ambio articles impacting environmental biogeochemistry research and knowledge : This article belongs to Ambio's 50th Anniversary Collection. Theme: Environmental contaminants.}, journal = {Ambio}, volume = {50}, number = {3}, pages = {539-543}, pmid = {33471250}, issn = {1654-7209}, mesh = {Anniversaries and Special Events ; Ecosystem ; Environmental Monitoring ; Humans ; *Pesticides/analysis ; *Polychlorinated Biphenyls/analysis ; }, abstract = {Reflections about three influential environmental contaminants papers published in Ambio are presented. The PCB Story by Jensen in (1972) had a very important influence on environmental chemistry. This is captured by way of comments and personal anecdotes. Wania's and MacKay's (1993) paper highlights the physical chemistry underlying transport of PCBs and organochlorine pesticides from temperate zone ecosystems to Polar Regions. Their paper exemplifies how principles of chemistry and environmental processes informed understanding the biogeochemical cycles of chemicals of environmental concern (CEC). Mergler et al.'s (2007) paper reviews knowledge of methyl mercury exposure and impacts in humans and served as an example of how to approach exposure and human health concerns for all CECs. All great progress. Then, the question: "How we missed for two decades the importance of plastics in the environment identified in a paper published the same year as The PCB Story? Are we missing yet another important environmental contaminant now?}, } @article {pmid33469254, year = {2021}, author = {Owens, JK and Hudson, AK}, title = {Prioritizing teacher emotions: shifting teacher training to a digital environment.}, journal = {Educational technology research and development : ETR & D}, volume = {69}, number = {1}, pages = {59-62}, pmid = {33469254}, issn = {1042-1629}, abstract = {This paper is in response to the manuscript entitled, "Success, failure and emotions: Examining the relationship between performance feedback and emotions in diagnostic reasoning," (Jarrell, Harley, Lajoie, & Naismith, Educational Technology & Research Development, 65, 1263-1284: 2017) from a K-12 teacher and administrator educational perspective. Jarrell et al.'s (Educational Technology & Research Development, 65, 1263-1284: 2017) findings indicate a strong relationship between outcome emotions and performance tasks: highest performing medical students had the most positive emotions. The authors suggested that medical students who fail and experience negative emotions could experience a loss of confidence and lead to dropping out of medical school. These results can be applied to teachers and administrators in K-12 settings as they make the shift to digital learning by including emotional assessments into the new digital learning platforms in order to address areas of emotional stress and teacher burnout before leading to attrition. This perspective makes suggestions of ways Jarrell et al.'s (Educational Technology & Research Development, 65, 1263-1284: 2017) findings could be a starting place for educational stakeholders to prioritize teachers' emotional well-being and offer an opportunity to provide intervention support in order to increase teacher self-efficacy in the shift to digital and possibly reduce teacher burnout.}, } @article {pmid33448108, year = {2021}, author = {Chang, MC and Choi, KH and Park, SG}, title = {Regarding Ke-Vin Chang et al.'s "Dynamic Ultrasound Imaging of the Brachial Plexus for Diagnosis of Thoracic Outlet Syndrome".}, journal = {Pain practice : the official journal of World Institute of Pain}, volume = {21}, number = {5}, pages = {606}, doi = {10.1111/papr.12994}, pmid = {33448108}, issn = {1533-2500}, mesh = {*Brachial Plexus/diagnostic imaging ; Humans ; *Thoracic Outlet Syndrome/diagnostic imaging ; Ultrasonography ; }, } @article {pmid33444437, year = {2021}, author = {Nicholls, SM and Aubrey, W and De Grave, K and Schietgat, L and Creevey, CJ and Clare, A}, title = {On the complexity of haplotyping a microbial community.}, journal = {Bioinformatics (Oxford, England)}, volume = {37}, number = {10}, pages = {1360-1366}, pmid = {33444437}, issn = {1367-4811}, support = {//BBSRC Institute Strategic Programme Grant/ ; BB/E/W/10964A01//Rumen Systems Biology/ ; R3192GFS//Meth-Abate project/ ; 818368//EC via Horizon 2020/ ; }, abstract = {MOTIVATION: Population-level genetic variation enables competitiveness and niche specialization in microbial communities. Despite the difficulty in culturing many microbes from an environment, we can still study these communities by isolating and sequencing DNA directly from an environment (metagenomics). Recovering the genomic sequences of all isoforms of a given gene across all organisms in a metagenomic sample would aid evolutionary and ecological insights into microbial ecosystems with potential benefits for medicine and biotechnology. A significant obstacle to this goal arises from the lack of a computationally tractable solution that can recover these sequences from sequenced read fragments. This poses a problem analogous to reconstructing the two sequences that make up the genome of a diploid organism (i.e. haplotypes) but for an unknown number of individuals and haplotypes.

RESULTS: The problem of single individual haplotyping was first formalized by Lancia et al. in 2001. Now, nearly two decades later, we discuss the complexity of 'haplotyping' metagenomic samples, with a new formalization of Lancia et al.'s data structure that allows us to effectively extend the single individual haplotype problem to microbial communities. This work describes and formalizes the problem of recovering genes (and other genomic subsequences) from all individuals within a complex community sample, which we term the metagenomic individual haplotyping problem. We also provide software implementations for a pairwise single nucleotide variant (SNV) co-occurrence matrix and greedy graph traversal algorithm.

Our reference implementation of the described pairwise SNV matrix (Hansel) and greedy haplotype path traversal algorithm (Gretel) is open source, MIT licensed and freely available online at github.com/samstudio8/hansel and github.com/samstudio8/gretel, respectively.}, } @article {pmid33442789, year = {2021}, author = {Bernardez, LA and de Oliveira, LEL and de Andrade Lima, LRP}, title = {Acid mine drainage at the Bahia Gold Belt (Brazil): microbial isolation and characterization.}, journal = {Environmental monitoring and assessment}, volume = {193}, number = {2}, pages = {60}, pmid = {33442789}, issn = {1573-2959}, support = {PNPD 2017//Coordenação de Aperfeiçoamento de Pessoal de Nível Superior/ ; Bolsa MSc//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; }, mesh = {Acidithiobacillus ; Brazil ; *Environmental Monitoring ; *Gold ; Mining ; Sulfides ; }, abstract = {Acid mine drainage occurs due to the chemical and microbiological oxidation of sulfide minerals and can be a source of potentially toxic elements contamination of groundwater and surface water. The objective of this study was to identify microorganisms involved in sulfide oxidation in the tailings of a Bahia Gold Belt mine (Brazil). Samples of solids and water were collected at the mine tailings dam and characterized. The microorganisms were isolated after enrichment and subsequent purification. The major constituents of the tailings are Si, Fe, Al, S, and K. The sulfur content of the tailings is 0.98%. The major phases are quartz, muscovite, and clinochlore. Gravity concentrates of the tailings show several particles of pyrite, that is, the major sulfide phase. Molecular analysis identified the microorganisms isolated in the acid mine drainage process in this region. Five bacterium species were found: Acidithiobacillus spp., Acidithiobacillus ferrooxidans, Acidiphilium spp., Leptospirillum type II, and Sulfobacillus spp. No organisms of the archaea or eukaryote domains were found. The isolate was used in the bioleaching of copper sulfide ore, and the copper extraction was about 60% in 60 days for ground ore.}, } @article {pmid33440449, year = {2021}, author = {Strauß, B and Brenk-Franz, K}, title = {[Attachment Characteristics and Speciality Choice among Medical Students].}, journal = {Psychotherapie, Psychosomatik, medizinische Psychologie}, volume = {71}, number = {6}, pages = {218-229}, doi = {10.1055/a-1322-3592}, pmid = {33440449}, issn = {1439-1058}, mesh = {Adult ; Career Choice ; Child ; Female ; Humans ; Male ; *Medicine ; Motivation ; Primary Health Care ; Specialization ; *Students, Medical ; Surveys and Questionnaires ; Young Adult ; }, abstract = {OBJECTIVES: Based upon a study by Ciechanowski et al. [27], a parallel survey was performed at the medical school of the University of Jena with the goal to determine a relationship between specialty choice and attachment characteristics among medical students.

METHOD: A sample of 411 medical students from different phases of the medical training (73,2% females, mean age: 22.7 yrs.) were asked about their current specialty choice and invited to describe themselves in three different attachment questionnaires. These were the Relationship Style Questionnaire (RSQ), the Bielefeld Partnership Expectation Questionnaire and the Relationship-specific Attachment Scales for adults in the versions related to the mother and the partner. In comparing subgroups, we first used Ciechanowski et al.'s [27] differentiation of specialty contrasting primary and non-primary care specialties. In addition, a categorization of Buddeberg-Fischer et al. [29] differentiating a total of 7 subgroups was used (general medicine, internal medicine, surgery, anesthesiology/emergency medicine, pediatrics, psychiatry/neurology and obstetrics/gynecology).

RESULTS: Comparing the groups according to Ciechanowski et al.'s categorization, differences occurred that were not replicating the original study: Students of the first subgroup (primary care) appeared to be more insecurely attached (according to the RSQ) and showed higher scores in subscales indicating dependency and preoccupation (e. g. fear of separation, dependently related to mother and partner). Similar as in Ciechanowski's study, the second group (non-primary care) revealed more individuals categorized as avoidant (or self-reliant). To differentiate the picture, the 7 categories according to Buddeberg-Fischer et al. [27] were compared. This comparison indicated that future pediatricians were classified as more insecure and ambivalent, whereas anesthesiologists more commonly were avoidant and dismissing. This picture was confirmed using comparisons of the questionnaire subscales. Since gender differences occurred both, related to specialty choice as well as attachment, gender was considered as a covariate in the analyses.

CONLUSIONS: In contrast to the study of Ciechanowski et al. [27], future pediatricians as part of the primary care group were characterized by a tendency to be dependent and preoccupied in all attachment measures, whereas the result of a tendency to be more avoidant and self-reliant among anesthesiologists and students choosing emergency medicine was more in line with the US-American study. Future research dealing with the motivation to choose specific fields of action in medicine should consider other psychological characteristics as well as biographical aspects.}, } @article {pmid33434342, year = {2021}, author = {Dawson, RL and Calear, AL and McCallum, SM and McKenna, S and Nixon, RDV and O'Kearney, R}, title = {The Emerging Literature on Exposure-Based Writing Therapies for Subthreshold and Clinical Posttraumatic Stress Disorder: A Response to Thompson-Hollands et al.'s (2020) Commentary on Dawson et al. (2020).}, journal = {Journal of traumatic stress}, volume = {34}, number = {1}, pages = {269-270}, doi = {10.1002/jts.22643}, pmid = {33434342}, issn = {1573-6598}, mesh = {Humans ; *Implosive Therapy ; Netherlands ; *Stress Disorders, Post-Traumatic ; Writing ; }, abstract = {Thompson-Hollands et al.'s (2020) commentary on our systematic review of exposure-based writing therapies for subthreshold and clinical posttraumatic stress symptoms (Dawson et al., 2020) emphasizes important questions about the impact of heterogeneity in drawing inferences from evidence reviews. In this reply, we discuss (a) our rationale for undertaking a systematic review that was broad rather than narrow in scope and (b) provide clarifications on how heterogeneity was considered in the meta-analyses that were conducted. We also strongly agree with Thompson-Hollands et al.'s recommendation that future research should focus on better understanding the mechanisms by which exposure-based writing therapies help reduce posttraumatic stress symptoms.}, } @article {pmid33413000, year = {2021}, author = {Vallortigara, G}, title = {Laterality for the next decade: Computational ethology and the search for minimal condition for cognitive asymmetry.}, journal = {Laterality}, volume = {26}, number = {3}, pages = {303-306}, doi = {10.1080/1357650X.2020.1870122}, pmid = {33413000}, issn = {1464-0678}, mesh = {Brain ; Cognition ; *Ethology ; *Functional Laterality ; }, abstract = {In this comment to Ocklenburg et al.'s paper I stressed the contribution that computational ethology can provide to the accurate tracking of lateralized behaviour in a variety of species; I also discussed how current interest in so-called «minimal cognition» may help to disentangle shared and species-specific mechanisms of brain and behavioural asymmetries.}, } @article {pmid33410456, year = {2021}, author = {Weiss, L and Jung, KM and Nalbandian, A and Llewellyn, K and Yu, H and Ta, L and Chang, I and Migliore, M and Squire, E and Ahmed, F and Piomelli, D and Kimonis, V}, title = {Ceramide contributes to pathogenesis and may be targeted for therapy in VCP inclusion body myopathy.}, journal = {Human molecular genetics}, volume = {29}, number = {24}, pages = {3945-3953}, pmid = {33410456}, issn = {1460-2083}, support = {R01 AR050236/AR/NIAMS NIH HHS/United States ; R56 AR050236/AR/NIAMS NIH HHS/United States ; }, mesh = {Animals ; Autophagy ; Ceramides/*metabolism ; *Disease Models, Animal ; Humans ; Inclusion Bodies/metabolism/*pathology ; Mice ; Muscle, Skeletal/metabolism/pathology ; Muscular Diseases/etiology/metabolism/*pathology ; Myoblasts/metabolism/*pathology ; Myositis, Inclusion Body/etiology/metabolism/*pathology ; Valosin Containing Protein/genetics/*metabolism ; }, abstract = {Knock-in homozygote VCPR155H/R155H mutant mice are a lethal model of valosin-containing protein (VCP)-associated inclusion body myopathy associated with Paget disease of bone, frontotemporal dementia and amyotrophic lateral sclerosis. Ceramide (d18:1/16:0) levels are elevated in skeletal muscle of the mutant mice, compared to wild-type controls. Moreover, exposure to a lipid-enriched diet reverses lethality, improves myopathy and normalizes ceramide levels in these mutant mice, suggesting that dysfunctions in lipid-derived signaling are critical to disease pathogenesis. Here, we investigated the potential role of ceramide in VCP disease using pharmacological agents that manipulate the ceramide levels in myoblast cultures from VCP mutant mice and VCP patients. Myoblasts from wild-type, VCPR155H/+ and VCPR155H/R155H mice, as well as patient-induced pluripotent stem cells (iPSCs), were treated with an inhibitor of ceramide degradation to increase ceramide via acid ceramidase (ARN082) for proof of principle. Three chemically distinct inhibitors of ceramide biosynthesis via serine palmitoyl-CoA transferase (L-cycloserine, myriocin or ARN14494) were used as a therapeutic strategy to reduce ceramide in myoblasts. Acid ceramidase inhibitor, ARN082, elevated cellular ceramide levels and concomitantly enhanced pathology. Conversely, inhibitors of ceramide biosynthesis L-cycloserine, myriocin and ARN14494 reduced ceramide production. The results point to ceramide-mediated signaling as a key contributor to pathogenesis in VCP disease and suggest that manipulating this pathway by blocking ceramide biosynthesis might exert beneficial effects in patients with this condition. The ceramide pathway appears to be critical in VCP pathogenesis, and small-molecule inhibitors of ceramide biosynthesis might provide therapeutic benefits in VCP and related neurodegenerative diseases.}, } @article {pmid33399216, year = {2021}, author = {Hay, P}, title = {Is orthorexia nervosa a healthy way of being or a mental health disorder? Commentary on He et al. (2020).}, journal = {The International journal of eating disorders}, volume = {54}, number = {2}, pages = {222-224}, doi = {10.1002/eat.23465}, pmid = {33399216}, issn = {1098-108X}, mesh = {Aged ; Feeding Behavior ; *Feeding and Eating Disorders/diagnosis/epidemiology ; Health Behavior ; Humans ; Male ; *Mental Health ; Prevalence ; }, abstract = {Orthorexia nervosa is a new syndrome that has seen a marked increase in research in the past decade. Very high prevalence estimates in non-clinical populations have fuelled the debate as to whether it is a disorder in its own right, or only a problem when occurring in the context of another mental health or eating disorder. More recent assessment instruments have gone some way to address this issue. However, He et al.'s (2020, International Journal of Eating Disorder) study in older East Asian persons was not supportive of orthorexia nervosa as a disorder. Rather, people with orthorexia nervosa had better physical and mental health and lower or similar levels of eating disorder features such as body dissatisfaction when compared with people who did not have orthorexia nervosa. Albeit that selection bias in participant recruitment may in part explain their findings, the status of orthorexia nervosa is unresolved. Further studies need to employ appropriate instruments that measure psychopathology and function more broadly and investigate people with orthorexia nervosa symptoms in representative populations with longitudinal designs. The last is critical, as the most compelling evidence supporting a disorder is to find an adverse health impact over time that can be avoided by appropriate intervention.}, } @article {pmid35282402, year = {2021}, author = {Meyer, M and Zosh, JM and McLaren, C and Robb, M and McCafferty, H and Golinkoff, RM and Hirsh-Pasek, K and Radesky, J}, title = {How educational are 'educational' apps for young children? App store content analysis using the Four Pillars of Learning framework.}, journal = {Journal of children and media}, volume = {15}, number = {4}, pages = {526-548}, pmid = {35282402}, issn = {1748-2798}, support = {K23 HD092626/HD/NICHD NIH HHS/United States ; R21 HD094051/HD/NICHD NIH HHS/United States ; }, abstract = {Experts have expressed concerns about the lack of evidence demonstrating that children's "educational" applications (apps) have educational value. This study aimed to operationalize Hirsh-Pasek, Zosh, et al.'s (2015) Four Pillars of Learning into a reliable coding scheme (Pillar 1: Active Learning, Pillar 2: Engagement in the Learning Process, Pillar 3: Meaningful Learning, Pillar 4: Social Interaction), describe the educational quality of commercially-available apps, and examine differences in educational quality between free and paid apps. We analyzed 100 children's educational apps with the highest downloads from Google Play and Apple app stores, as well as 24 apps most frequently played by preschool-age children in a longitudinal cohort study. We developed a coding scheme in which each app earned a value of 0-3 for each Pillar, defining lower-quality apps as those scoring ≤ 4, summed across the Four Pillars. Overall scores were low across all Pillars. Free apps had significantly lower Pillar 2 (Engagement in Learning Process) scores (t-test, p < .0001) and overall scores (t-test, p < .0047) when compared to paid apps, due to the presence of distracting enhancements. These results highlight the need for improved design of educational apps guided by developmental science.}, } @article {pmid33350576, year = {2021}, author = {Pruett, TL}, title = {COVID-19 and transplantation: Fatigue and responsibility.}, journal = {American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons}, volume = {21}, number = {6}, pages = {2002-2003}, pmid = {33350576}, issn = {1600-6143}, mesh = {*COVID-19 ; Fatigue ; Humans ; SARS-CoV-2 ; Tissue Donors ; *Tissue and Organ Procurement ; Waiting Lists ; }, abstract = {The US transplantation and donation community needs COVID-19–specific information to guide safe and effective transplant care during the pandemic. Goff et al.’s article is on page 2100.}, } @article {pmid33338997, year = {2021}, author = {Moreno-Madueño, G and Rivero-Garvía, M and Tirado-Caballero, J and Márquez-Rivas, J}, title = {Diastematobulbia type II without associated dermoid tumor: case report.}, journal = {Journal of neurosurgery. Pediatrics}, volume = {27}, number = {3}, pages = {311-316}, doi = {10.3171/2020.7.PEDS20161}, pmid = {33338997}, issn = {1933-0715}, mesh = {Child Development ; Dermoid Cyst/*pathology ; Female ; Humans ; Infant, Newborn ; Magnetic Resonance Imaging ; Medulla Oblongata/abnormalities/pathology ; Meningocele/pathology ; Meningomyelocele/surgery ; Neural Tube Defects/pathology/surgery ; Neurosurgical Procedures ; Notochord/abnormalities/pathology ; Pregnancy ; Spina Bifida Occulta/pathology ; Spinal Cord/abnormalities ; Spinal Dysraphism/*pathology/surgery ; Young Adult ; }, abstract = {Split cord malformation (SCM) is a term used for all double spinal cords. It represents 3.8%-5% of spinal dysraphisms. Pang et al.'s embryological theory proposes the formation of an "accessory neurenteric canal" that communicates with the yolk sac and amnion. To the authors' knowledge, only three cases of diastematobulbia (basicranial SCM) associated with a spur or dermoid have been reported in the literature.The case patient is a newborn girl with an occipitocervical meningocele and dermal sinus associated with an anomaly of notochordal development in the transition between the medulla oblongata and the spinal cord (diastematobulbia) without a bony septum or dermoid cyst. The patient also has agenesis of the atlas and an absence of corticospinal tract decussation. This patient underwent reconstruction of the occipital meningocele and dermal sinus excision.To the authors' knowledge, this is the first described case of type II diastematobulbia (basicranial SCM), without a dermoid cyst. The authors analyzed the embryological errors present in the case patient and considered the option of further surgical treatment depending on the evolution of the patient's condition. At the time of this report, the patient had shown normal psychomotor development. However, this fact may only be due to the patient's young age. Considering that after initial untethering the patient remained clinically asymptomatic, conservative and close surveillance has been and continues to be the proposed treatment.}, } @article {pmid33329229, year = {2020}, author = {Dhami, MK and Weiss-Cohen, L and Ayton, P}, title = {Are People Experiencing the 'Pains of Imprisonment' During the COVID-19 Lockdown?.}, journal = {Frontiers in psychology}, volume = {11}, number = {}, pages = {578430}, pmid = {33329229}, issn = {1664-1078}, abstract = {BACKGROUND: By the end of March 2020, more than a fifth of the world's population was in various degrees of "lockdown" in order to slow the spread of COVID-19. This enforced confinement led some to liken lockdown to imprisonment. We directly compared individual's experiences of lockdown with prisoners' experiences of imprisonment in order to determine whether psychological parallels can be drawn between these two forms of confinement.

METHODS: Online surveys of adults in lockdown in the UK (N = 300) and California (N = 450) were conducted 4 and 5 weeks into lockdown in each region, respectively. The UK data was then compared to Souza and Dhami's (2010) sample of 267 medium security prisoners in England, and the Californian data was compared to Dhami et al.'s (2007) sample of 307 medium security Federal prisoners in California. We measured the effects of Group (Lockdown v. Prison) on five categories of dependent variables (i.e., activity, social contact, thoughts, feelings, and rule-breaking), controlling for demographic differences between the groups.

RESULTS: In both regions, people in lockdown thought significantly less often about missing their freedom, as well as missing their family and friends living elsewhere than did first-time prisoners. However, people in lockdown in both regions were also significantly less engaged in a range of daily activities than were first-time prisoners. Additionally, in both regions, people in lockdown reported feeling more hopeless than first-time prisoners.

CONCLUSION: Although Governments introducing lockdown policies do not intend to punish their citizens as courts do when sending convicted offenders to prison, such policies can have unintended adverse consequences. Psychological parallels can be drawn between the two forms of confinement.}, } @article {pmid33029572, year = {2020}, author = {Moloney, B and Kroll, T and Lafferty, A}, title = {An exploration of young carers' experiences of school and their perceptions regarding their future career - a scoping review protocol.}, journal = {HRB open research}, volume = {3}, number = {}, pages = {41}, pmid = {33029572}, issn = {2515-4826}, abstract = {Background: Young carers are young people who care for a relative or a friend with an illness, disability, frailty, a mental health issue or addiction. Across the world, it is challenging to calculate the exact numbers due to the invisible nature of their role that can exist due to stigmatisation and fear of authoritative intrusion. As young carers reach 16 years and over, future career prospects become more significant. Young carers are more likely than their peers not to be in education, employment, or training and are more likely to do poorly at school or college than their non-caregiving peers due to the demands of caring. Recognising that positive engagement at school is a vital correlate of positive employment outcomes, young carers are at risk as their caring role can limit the range of employment opportunities open to them. This paper outlines the protocol for a robust synthesis of the literature surrounding young carers and their career perceptions. The scoping review will address the research question 'What is known from the literature about young carers in school and their career perceptions?' The overall aim of this paper is to present a protocol for the scoping review to map the key concepts, types of evidence, and gaps in research related to young carers in school and their future careers. Methods: The review will follow Arksey and O'Malley (2005) and Levac et al.'s, (2010) scoping review framework. The steps involved include: (1) research question identification; (2) relevant studies identification; (3) selection of studies; (4) data charting; (5) collating, summarising and reporting the results; and (6) stakeholders' consultation. Conclusions: The scoping review is an appropriate first step to employ in presenting the literature to inform a larger research study on young carers' experiences in school and their perceptions regarding their future careers.}, } @article {pmid33324529, year = {2020}, author = {Rose-Reneau, Z and Moorefield, AK and Schirmer, D and Ismailov, E and Downing, R and Wright, BW}, title = {The Critical Shoulder Angle as a Diagnostic Measure for Osteoarthritis and Rotator Cuff Pathology.}, journal = {Cureus}, volume = {12}, number = {11}, pages = {e11447}, pmid = {33324529}, issn = {2168-8184}, abstract = {The purpose of this study was to correlate critical shoulder angle (CSA), a measurement that takes into account both glenoid tilt and the acromial index (AI), with shoulder pathologies as presented in an earlier study by Moor et al. (2013). Based on Moor et al.'s predicted normal CSA range of 30-35°, we hypothesized that a greater-than-normal CSA would be correlated to or associated with rotator cuff pathology, while a smaller-than-normal CSA would be associated with osteoarthritis (OA). Following Moore et al., we utilized Grashey radiographic imaging because it provides the clearest view of the entire glenoid fossa and acromion. We analyzed 323 anterior-posterior (AP) radiographs to identify and measure the CSA, classifying each patient into one of five groups [none reported (n=94), mild OA (n=156), moderate OA (n=36), severe OA (n=37), and rotator cuff pathology (n=40)]. Our results were statistically significant, supporting the association of smaller CSAs with OA and larger CSAs with rotator cuff pathology. CSA measurements could provide a new means for identifying shoulder pathology and thereby reduce the need for costly and timely imaging techniques. CSA values could also provide useful information to utilize preventatively with interventions such as physical therapy to alter the CSA and reduce the prevalence of OA and shoulder arthroplasties. This study builds on the findings of Moore et al. in creating a correlation between CSA and shoulder pathology.}, } @article {pmid33313595, year = {2020}, author = {Sharma, S and Bhalotra, AR and Awal, S}, title = {Re: Attribution of Delayed Poor Lung Function to Desflurane-Based Balanced Anaesthesia Might be Inappropriate: Our Reply to Sharma et al.'s article.}, journal = {Turkish journal of anaesthesiology and reanimation}, volume = {48}, number = {6}, pages = {512-513}, pmid = {33313595}, issn = {2667-677X}, } @article {pmid33313594, year = {2020}, author = {Karim, HMR and Bhakta, P}, title = {Attribution of Delayed Poor Lung Function to Desflurane-Based Balanced Anaesthesia Might be Inappropriate: Our Reply to Sharma et al.'s Article.}, journal = {Turkish journal of anaesthesiology and reanimation}, volume = {48}, number = {6}, pages = {511-512}, pmid = {33313594}, issn = {2667-677X}, } @article {pmid33310159, year = {2021}, author = {Zima, BT}, title = {Editorial: The Cost of Comorbid Child Psychiatric Disorders: A National Call to Achieve the Triple Aim for Child Mental Health Care.}, journal = {Journal of the American Academy of Child and Adolescent Psychiatry}, volume = {60}, number = {3}, pages = {336-337}, doi = {10.1016/j.jaac.2020.12.004}, pmid = {33310159}, issn = {1527-5418}, mesh = {Canada/epidemiology ; Child ; Hospitalization ; Hospitals ; Humans ; *Inpatients ; *Mental Disorders/epidemiology/therapy ; Mental Health ; }, abstract = {The National Quality Strategy to transform the US health care system is predicated upon Donald Berwick et al.'s "Triple Aim" envisioning the simultaneous pursuit of improved care, better population health, and reduced costs.[1] More recently, emphasis has been placed on improving the value of health care as defined by "achieving the best patient health outcomes (quality + experience) at the lowest cost."[2] US health care expenditures are projected to grow at an average annual rate of 5.4% during this decade, reaching 19.7% of the gross domestic product or an estimated 6.1 billion dollars by 2028.[3] Compared with 36 high-income countries, including Canada, the US spends nearly twice as much on health care yet has the lowest life expectancy and highest suicide rate.[4] However, solely targeting reduction in mental health care costs is not a solution, because the mental and general health care systems are inextricably linked[5] and for children span multiple care sectors (eg, schools, child welfare, juvenile justice). In this issue of the Journal, Ansari et al.[6] validates the complexity of physically ill children with a comorbid psychiatric disorder among more than 50,000 admissions to an acute-care pediatric specialty hospital within Canada's publicly funded health care system. Almost one out of 10 admissions for a physical illness had a documented comorbid psychiatric disorder, which is consistent with US pediatric hospital discharges.[7] Children who were older, more clinically complex, and with prior hospitalizations were more likely to be among inpatient admissions with a comorbid psychiatric disorder. With outstanding methodologic rigor, the data suggest that pediatric inpatient admissions with comorbid psychiatric disorders had a nearly 10% longer length of stay and higher costs per admission compared with inpatient admissions without a comorbid psychiatric disorder---a difference in total cumulative costs of more than CAN$11.3 million (equivalent of about US$8.4 million).}, } @article {pmid33308154, year = {2020}, author = {Christensen, HS and Borgbjerg, J and Børty, L and Bøgsted, M}, title = {On Jones et al.'s method for extending Bland-Altman plots to limits of agreement with the mean for multiple observers.}, journal = {BMC medical research methodology}, volume = {20}, number = {1}, pages = {304}, pmid = {33308154}, issn = {1471-2288}, abstract = {BACKGROUND: To assess the agreement of continuous measurements between a number of observers, Jones et al. introduced limits of agreement with the mean (LOAM) for multiple observers, representing how much an individual observer can deviate from the mean measurement of all observers. Besides the graphical visualisation of LOAM, suggested by Jones et al., it is desirable to supply LOAM with confidence intervals and to extend the method to the case of multiple measurements per observer.

METHODS: We reformulate LOAM under the assumption the measurements follow an additive two-way random effects model. Assuming this model, we provide estimates and confidence intervals for the proposed LOAM. Further, this approach is easily extended to the case of multiple measurements per observer.

RESULTS: The proposed method is applied on two data sets to illustrate its use. Specifically, we consider agreement between measurements regarding tumour size and aortic diameter. For the latter study, three measurement methods are considered.

CONCLUSIONS: The proposed LOAM and the associated confidence intervals are useful for assessing agreement between continuous measurements.}, } @article {pmid33303292, year = {2021}, author = {Haslam, SA and Haslam, C and Jetten, J and Cruwys, T and Bentley, SV}, title = {Rethinking the nature of the person at the heart of the biopsychosocial model: Exploring social changeways not just personal pathways.}, journal = {Social science & medicine (1982)}, volume = {272}, number = {}, pages = {113566}, doi = {10.1016/j.socscimed.2020.113566}, pmid = {33303292}, issn = {1873-5347}, mesh = {*COVID-19 ; Humans ; *Pandemics ; SARS-CoV-2 ; }, abstract = {Karunamuni et al.'s (2020) biopsychosocial-pathways (BPS-P) model provides an important framework for elaborating on Engel's (1977) biopsychosocial (BPS) model of health. In particular, the BPS-P model improves on Engel's by articulating and evidencing the multiple pathways between biological, psychological, and social influences on health and identifying mechanisms that might be implicated in these pathways. Yet its analytic treatment of these influences as "separate systems" means that, as with Engel's model, the BPS-P model is more a list of ingredients than an integrated whole. In this commentary, following Haslam et al.'s (2019) specification of a sociopsychobio model, we underscore the value of a synthetic appreciation of biology, psychology, and society as dynamically interdependent aspects of an integrated whole which is more than just the sum of its parts and the pathways between them. In particular, our alternative framework centres on an appreciation of people as social beings whose group memberships and associated social identities open up 'changeways' (not just pathways) that, as we have seen during the COVID-19 pandemic, can fundamentally restructure biology, psychology and society.}, } @article {pmid33301344, year = {2020}, author = {}, title = {"Group therapy for schizophrenia: A meta-analysis": Correction to Burlingame et al. (2020).}, journal = {Psychotherapy (Chicago, Ill.)}, volume = {57}, number = {4}, pages = {597}, doi = {10.1037/pst0000354}, pmid = {33301344}, issn = {1939-1536}, abstract = {Reports an error in "Group therapy for schizophrenia: A meta-analysis" by Gary M. Burlingame, Hal Svien, Lars Hoppe, Isaac Hunt and Jenny Rosendahl (Psychotherapy, 2020[Jun], Vol 57[2], 219-236). In the article, the Orfanos et al. (2015) meta-analysis was missing from Burlingame et al. (2020) and should have appeared as Footnote 1 at the end of the abstract. Consistent with Orfanos et al. (2015), the Burlingame et al. (2020) findings support the notion that group treatments can improve negative symptoms of schizophrenia, across active and passive controls. Unlike Orfanos et al.'s (2015) study, Burlingame et al. (2020) also found a significant effect size for positive symptoms. Reference Orfanos, S., Banks, C., & Priebe, S. (2015). Are group psychotherapeutic treatments effective for patients with schizophrenia? A systematic review and meta-analysis. Psychotherapy and Psychosomatics, 84, 241-249. https://doi.org/10.1159/ 000377705. Footnote 2 was missing from the end of the first sentence in the Method section. This meta-analysis is not registered with PROSPERO, and the PROSPERO protocol (CRD42013004419) does not include the disorder of schizophrenia... (The following abstract of the original article appeared in record 2020-37337-001.) The effectiveness of group treatments for people with schizophrenia has not been examined on symptom-specific (positive and negative symptoms) outcomes, and the differential effects of the most popular group treatments remain unknown. We conducted a meta-analysis of randomized controlled trials that tested (a) the effectiveness of 7 frequently used group treatments on positive and negative symptoms and (b) if treatment-specific outcome improvement was associated with improvement on schizophrenia symptoms. Major databases were searched from 1990 to 2018 for randomized controlled trials of group treatment for people with schizophrenia, including first-episode psychosis. A random effects meta-analysis and meta-regression was conducted on 52 studies representing 4,156 individuals that produced a significant, small effect on symptom-specific outcomes (g = 0.30), with 4 group treatments (cognitive remediation, multifamily, psychoeducational, and social skills training) posting significant improvement. In addition, change on treatment-specific outcomes explained 16% of schizophrenia symptom and 44% of general functioning improvement. Results are discussed with respect to how they replicate past meta-analytic findings and possible revision of practice guidelines to incorporate evidence-based group treatments for schizophrenia. (PsycInfo Database Record (c) 2020 APA, all rights reserved).}, } @article {pmid33286371, year = {2020}, author = {Liu, Y and Wang, L and Shen, X and Li, L}, title = {New Constructions of Identity-Based Dual Receiver Encryption from Lattices.}, journal = {Entropy (Basel, Switzerland)}, volume = {22}, number = {6}, pages = {}, pmid = {33286371}, issn = {1099-4300}, support = {61972050//National Natural Science Foundation of China/ ; 2018CXGC0701//Shandong Provincial Key Research and Development Program of China/ ; CX2019119, CX2019233//BUPT Excellent Ph.D. Students Foundation/ ; }, abstract = {Dual receiver encryption (DRE), being originally conceived at CCS 2004 as a proof technique, enables a ciphertext to be decrypted to the same plaintext by two different but dual receivers and becomes popular recently due to itself useful application potentials such secure outsourcing, trusted third party supervising, client puzzling, etc. Identity-based DRE (IB-DRE) further combines the bilateral advantages/facilities of DRE and identity-based encryption (IBE). Most previous constructions of IB-DRE are based on bilinear pairings, and thus suffers from known quantum algorithmic attacks. It is interesting to build IB-DRE schemes based on the well-known post quantum platforms, such as lattices. At ACISP 2018, Zhang et al. gave the first lattice-based construction of IB-DRE, and the main part of the public parameter in this scheme consists of 2 n + 2 matrices where n is the bit-length of arbitrary identity. In this paper, by introducing an injective map and a homomorphic computation technique due to Yamada at EUROCRYPT 2016, we propose another lattice-based construction of IB-DRE in an even efficient manner: The main part of the public parameters consists only of 2 p n 1 p + 2 matrices of the same dimensions, where p (≥ 2) is a flexible constant. The larger the p and n, the more observable of our proposal. Typically, when p = 2 and n = 284 according to the suggestion given by Peikert et al., the size of public parameters in our proposal is reduced to merely 12% of Zhang et al.'s method. In addition, to lighten the pressure of key generation center, we extend our lattice-based IB-DRE scheme to hierarchical scenario. Finally, both the IB-DRE scheme and the HIB-DRE scheme are proved to be indistinguishable against adaptively chosen identity and plaintext attacks (IND-ID-CPA).}, } @article {pmid33281425, year = {2021}, author = {Assaf, N}, title = {Instructional interface's blueprint for guiding instructional-technological interactions' research: the Big Bang shift in K-12.}, journal = {Educational technology research and development : ETR & D}, volume = {69}, number = {1}, pages = {207-211}, pmid = {33281425}, issn = {1042-1629}, abstract = {This response reviews and analyzes the ten focal topics and three elements introduced in Nacu, Martin, and Pinkard's work, entitled "Designing for 21st century learning online: a heuristic method to enable educator learning support roles". An analogy of the London Stock Exchange's Big Bang is drawn to describe the moment education is currently living. In this context, homeschooling guided learning is analyzed. Nacu, Martin, and Pinkard (2018) offered insightful approaches for the sudden shift to digital that the world has experienced since April 2020. Their inquiries coincided with the questions asked by researchers and teachers around the world when their schools were closed due to the COVID-19 lockdown. Along with Nacu et al.'s (Educ Tech Res 64(4):1029-1049, 2018) effort, a theoretical framework, an instructional interface model, is conceptualized as a blueprint, to offer a guide for research for instructional-technological interactions. In this scenario, shifting to digital is not just a tech shift but a worldwide creators' mindset shifts.}, } @article {pmid33276853, year = {2020}, author = {Jiang, Y and Kim, SI and Bong, M}, title = {The role of cost in adolescent students' maladaptive academic outcomes.}, journal = {Journal of school psychology}, volume = {83}, number = {}, pages = {1-24}, doi = {10.1016/j.jsp.2020.08.004}, pmid = {33276853}, issn = {1873-3506}, mesh = {*Academic Success ; Adolescent ; Educational Status ; Female ; Humans ; Male ; Mathematics ; Motivation ; Republic of Korea ; Schools ; Students/*psychology ; }, abstract = {Motivation wields a tangible impact on students' academic functioning. Among the theoretical frameworks used to explain students' motivation to learn, Eccles et al.'s expectancy-value theory (1983) is one of the most influential. It has been used to investigate students' competence- and value-related beliefs and how they are associated with academic-related choices, learning behaviors, and achievement. In the learning context, cost has mostly been discussed under the expectancy-value framework as a sub-dimension of task value and conceptualized as reflecting the negative aspects of task engagement. The issue of cost has recently attracted growing interest among scholars, providing a way to explain the dynamics of student motivation. However, cost is still underexplored in the empirical literature. In the present study, we assessed adolescent students' perceived cost (i.e., effort cost, opportunity cost, ego cost, and emotional cost) of studying math and examined its unique relations with academic motivation and achievement. Across a series of three studies, we found that cost is empirically distinct from the utility, attainment, and interest components of task value and is closely related to students' maladaptive academic outcomes. In particular, cost showed unique associations with adolescent students' test anxiety, disorganization, adoption of avoidance goals, avoidance intentions, and academic achievement. The present study's findings highlight the importance of including cost as a unique construct alongside value to more fully capture students' motivational dynamics in school.}, } @article {pmid33253353, year = {2021}, author = {Huang, YX and Wang, WX and Tang, YP and Yue, SJ}, title = {Drug repurposing for COVID-19: could vitamin C combined with glycyrrhizic acid be at play by the findings of Li et al.'s database-based network pharmacology analysis?.}, journal = {Briefings in bioinformatics}, volume = {22}, number = {2}, pages = {1508-1510}, pmid = {33253353}, issn = {1477-4054}, mesh = {Ascorbic Acid/administration & dosage/*therapeutic use ; COVID-19/virology ; *Databases, Pharmaceutical ; *Drug Repositioning ; Glycyrrhizic Acid/administration & dosage/*therapeutic use ; Humans ; SARS-CoV-2/isolation & purification ; *COVID-19 Drug Treatment ; }, abstract = {The outbreak and pandemic of SARS-CoV-2 in 2019 has caused a severe public health burden and will challenge global health for the future. The discovery and mechanistic investigation of drugs against Coronavirus disease 2019 (COVID-19) is in deadly demand. The paper published by Li and colleagues proposed the hypothesis that vitamin C combined with glycyrrhizic acid in treating COVID-19 and its mechanistic investigation was performed by a database-based network pharmacology. In this letter, we present critical comments on the limitations and insufficiencies involved, from both the perspective of network pharmacology and current evidence on COVID-19.}, } @article {pmid33250613, year = {2021}, author = {Stefaniak, J}, title = {Policy and contextual considerations for enabling learning support roles in digital environments.}, journal = {Educational technology research and development : ETR & D}, volume = {69}, number = {1}, pages = {221-225}, pmid = {33250613}, issn = {1042-1629}, abstract = {This paper is in response to Nacu et al.'s (Educ Technol Res Dev 66(4):1029-1049, 2018) guidelines to enable educators to fulfill learner support roles in online education from a contextual perspective and how their heuristic method can be utilized in today's current pandemic. It also explores how learner support roles can be leveraged to balance affordances offered by the learning environment and the learners themselves. Additionally, this paper discusses the implications for addressing social inequities in digital environments and education policy reform.}, } @article {pmid33250608, year = {2021}, author = {Lohman, L}, title = {Build, buy, or rent? A systems view of faculty design work in the digital learning era.}, journal = {Educational technology research and development : ETR & D}, volume = {69}, number = {1}, pages = {277-280}, pmid = {33250608}, issn = {1042-1629}, abstract = {To suggest sound practices in obtaining the faculty design talent needed to rapidly deploy or scale up digital learning, this paper adopts a systems view of the findings and implications of "The Process of Designing for Learning: Understanding University Teachers' Design Work" by Bennett et al. (Educational Technology Research and Development 65(1), 125-145, 2017). Bennett et al.'s article makes an important contribution to our growing understanding of faculty capacity for and approaches to course design. Their work establishes faculty roles as designers, which is an essential consideration as institutions seek digital design talent. Nevertheless, important limitations of their research are limited detail about faculty design skills and an emphasis on how faculty design resembles others' design approaches. This paper suggests specific ways that institutions can apply and extend insights from Bennett et al.'s research to cultivate faculty design talents in nimble responses to large-scale or rapid shifts to digital learning through practices of professional development and strategic faculty hiring.}, } @article {pmid33250212, year = {2021}, author = {Alizadeh, M and Moghaddam, MM and HosseinNia, SH}, title = {A novel zero delay low pass filter: Application to precision positioning systems.}, journal = {ISA transactions}, volume = {111}, number = {}, pages = {231-248}, doi = {10.1016/j.isatra.2020.11.013}, pmid = {33250212}, issn = {1879-2022}, abstract = {In this paper, a nonlinear low-pass filter is presented, which produces significantly less phase lag than linear and some nonlinear filters. The proposed filter employs a saturation function to enhance the linear filter's performance. The gain and phase responses of the filter are derived analytically using a modified describing function, and the efficiency of the proposed method is examined through numerical examples. Based on the required cut-off frequency and noise to signal ratio, a rule of thumb is given to set the filter's parameters. In the frequency domain, simulation results show that the filter's gain response is near 0dB in the pass-band, and the noise attenuation rate is -40dB∕dec, while the phase lag is three times lesser compared to 2[nd] order Butterworth low-pass filter. Moreover, comparing with Jin et al.'s parabolic sliding mode filter and feed-forwarded parabolic sliding mode filter the gain and phase of the proposed filter are closer to zero in the pass-band and before cut-off frequency. Furthermore, the filter's performance is also evaluated in case of different noise color and concluded that the proposed filter is superior to linear and nonlinear filters in case of white, blue, or purple noise Finally, the filter's effectiveness and the tuning guideline are validated by simulating a precision motion control system in the discrete-time domain.}, } @article {pmid33239440, year = {2021}, author = {Kmetzsch, V and Anquetil, V and Saracino, D and Rinaldi, D and Camuzat, A and Gareau, T and Jornea, L and Forlani, S and Couratier, P and Wallon, D and Pasquier, F and Robil, N and de la Grange, P and Moszer, I and Le Ber, I and Colliot, O and Becker, E and , }, title = {Plasma microRNA signature in presymptomatic and symptomatic subjects with C9orf72-associated frontotemporal dementia and amyotrophic lateral sclerosis.}, journal = {Journal of neurology, neurosurgery, and psychiatry}, volume = {92}, number = {5}, pages = {485-493}, pmid = {33239440}, issn = {1468-330X}, mesh = {Adult ; Aged ; Amyotrophic Lateral Sclerosis/blood/genetics/*metabolism ; Biomarkers/blood ; C9orf72 Protein/*genetics ; Disease Progression ; Female ; Frontotemporal Dementia/blood/genetics/*metabolism ; Humans ; Male ; MicroRNAs/*blood ; Middle Aged ; Mutation ; Exome Sequencing ; }, abstract = {OBJECTIVE: To identify potential biomarkers of preclinical and clinical progression in chromosome 9 open reading frame 72 gene (C9orf72)-associated disease by assessing the expression levels of plasma microRNAs (miRNAs) in C9orf72 patients and presymptomatic carriers.

METHODS: The PREV-DEMALS study is a prospective study including 22 C9orf72 patients, 45 presymptomatic C9orf72 mutation carriers and 43 controls. We assessed the expression levels of 2576 miRNAs, among which 589 were above noise level, in plasma samples of all participants using RNA sequencing. The expression levels of the differentially expressed miRNAs between patients, presymptomatic carriers and controls were further used to build logistic regression classifiers.

RESULTS: Four miRNAs were differentially expressed between patients and controls: miR-34a-5p and miR-345-5p were overexpressed, while miR-200c-3p and miR-10a-3p were underexpressed in patients. MiR-34a-5p was also overexpressed in presymptomatic carriers compared with healthy controls, suggesting that miR-34a-5p expression is deregulated in cases with C9orf72 mutation. Moreover, miR-345-5p was also overexpressed in patients compared with presymptomatic carriers, which supports the correlation of miR-345-5p expression with the progression of C9orf72-associated disease. Together, miR-200c-3p and miR-10a-3p underexpression might be associated with full-blown disease. Four presymptomatic subjects in transitional/prodromal stage, close to the disease conversion, exhibited a stronger similarity with the expression levels of patients.

CONCLUSIONS: We identified a signature of four miRNAs differentially expressed in plasma between clinical conditions that have potential to represent progression biomarkers for C9orf72-associated frontotemporal dementia and amyotrophic lateral sclerosis. This study suggests that dysregulation of miRNAs is dynamically altered throughout neurodegenerative diseases progression, and can be detectable even long before clinical onset.

TRIAL REGISTRATION NUMBER: NCT02590276.}, } @article {pmid33231790, year = {2021}, author = {Modell, SM and Fleming, PJ and Lopez, WD and Goltz, HH}, title = {Work in Progress: Immigrant Health Care from the Vantage of Cancer Testing and Screening.}, journal = {Journal of immigrant and minority health}, volume = {23}, number = {1}, pages = {1-3}, pmid = {33231790}, issn = {1557-1920}, mesh = {Early Detection of Cancer ; *Emigrants and Immigrants ; Health Services Accessibility ; Humans ; Insurance Coverage ; Insurance, Health ; Medicaid ; *Neoplasms/diagnosis ; Patient Protection and Affordable Care Act ; United States ; }, abstract = {This letter offers a perspective from cancer testing and screening on the improvements in immigrant insurance coverage and care charted in Bustamante et al.'s April 2019 article in JOIH on "Health Care Access and Utilization Among U.S. Immigrants Before and After the Affordable Care Act." Supportive evidence for their data may be found in complementary literature drawing from both the National Health Interview Survey the authors use and the Medical Expenditure Panel Survey, while post-ACA surveys and state level information suggest disparities remain for lawfully present and undocumented immigrants ineligible for Medicaid and unable to secure insurance to pay medical costs. Existent options for cancer services are discussed. Further relevant reform depends on voter awareness and collaborative efforts between consumer advocates and legislators.}, } @article {pmid33225440, year = {2021}, author = {Lionello-DeNolf, KM}, title = {An update on the search for symmetry in nonhumans.}, journal = {Journal of the experimental analysis of behavior}, volume = {115}, number = {1}, pages = {309-325}, doi = {10.1002/jeab.647}, pmid = {33225440}, issn = {1938-3711}, mesh = {Animals ; *Columbidae ; *Discrimination Learning ; Rats ; }, abstract = {Sidman et al.'s (1982) failure to find evidence for symmetry (bidirectional associations between stimuli) in monkeys and baboons set the stage for decades of work on emergent relations in nonhumans. They attributed the failure to the use of procedures that did not (1) promote stimulus control based on the relation between the sample and correct comparison and (2) reduce control by irrelevant stimulus features. Previous reviews of symmetry in nonhumans indicated that multiple exemplar training and successive matching might encourage appropriate stimulus control. This review examined 16 studies that investigated symmetry in 94 subjects, including pigeons, rats, capuchin monkeys, and baboons. Several studies used alternative training procedures to minimize sources of irrelevant stimulus control, and many combined multiple exemplar training with other procedural modifications. Symmetry was observed in approximately 30% of subjects. Studies that reported the strongest evidence for symmetry used successive matching-to-sample procedures that included training on both symbolic and identity relations, and studies finding mixed evidence employed alternative methods. These studies highlight the challenge in creating training procedures that promote symmetry and the need to assess the underlying sources of control on positive demonstrations.}, } @article {pmid33220348, year = {2021}, author = {Del Giudice, M}, title = {Åhs et al.'s (2018) Systematic review on biological preparedness and resistance to extinction: A commentary and reanalysis.}, journal = {Neuroscience and biobehavioral reviews}, volume = {120}, number = {}, pages = {13-15}, doi = {10.1016/j.neubiorev.2020.11.009}, pmid = {33220348}, issn = {1873-7528}, mesh = {Animals ; *Fear ; }, } @article {pmid33199950, year = {2021}, author = {Howard, NR}, title = {"How Did I Do?": Giving learners effective and affective feedback.}, journal = {Educational technology research and development : ETR & D}, volume = {69}, number = {1}, pages = {123-126}, pmid = {33199950}, issn = {1042-1629}, abstract = {Borup et al. (Educ Technol Res Dev 63: 161-184. 10.1007/s11423-015-9367-8, 2015) examined teacher candidate and instructor perceptions of feedback in blended learning environments. Their work juxtaposed two different modalities of learning and feedback; it serves as a critical anchor to support future efforts to ensure students and instructors are engaged in an efficient feedback experience that offers affective benefits in digital learning spaces. In this article, I offer applicable feedback delivery strategies for educators as an extension of Borup et al.'s work.}, } @article {pmid33197639, year = {2021}, author = {Karim, HMR and Esquinas, AM}, title = {Our insight about Mukhtar et al.'s outcome of non-invasive ventilation in COVID-19 critically ill patients.}, journal = {Anaesthesia, critical care & pain medicine}, volume = {40}, number = {1}, pages = {100781}, pmid = {33197639}, issn = {2352-5568}, mesh = {*COVID-19 ; Critical Illness/therapy ; Humans ; Intensive Care Units ; *Noninvasive Ventilation ; Respiration, Artificial ; Retrospective Studies ; SARS-CoV-2 ; }, } @article {pmid33194954, year = {2020}, author = {Frahsa, A and Farquet, R and Bayram, T and De Araujo, L and Meyer, S and Sakarya, S and Cattacin, S and Abel, T}, title = {Experiences With Health Care Services in Switzerland Among Immigrant Women With Chronic Illnesses.}, journal = {Frontiers in public health}, volume = {8}, number = {}, pages = {553438}, pmid = {33194954}, issn = {2296-2565}, mesh = {Chronic Disease ; *Emigrants and Immigrants ; Female ; Health Services Accessibility ; Humans ; *Maternal Health Services ; Pregnancy ; Switzerland ; }, abstract = {Introduction: Descriptive data indicate a high burden of chronic illness among immigrant women in Switzerland. Little is known about how immigrant women with chronic illnesses experience healthcare services. This paper presents a methodological approach theoretically informed by Sen's capability approach and Levesque's framework of access to healthcare to study patient-reported experiences (PREs) of Swiss healthcare services among immigrant women with chronic conditions. Methods: We conducted 48 semi-structured qualitative interviews in Bern and Geneva with Turkish (n = 12), Portuguese (n = 12), German (n = 12), and Swiss (n = 12) women. Participants were heterogenous in age, length of stay, SES, and educational attainment, illness types and history. We also conducted semi-structured interviews with healthcare and social service providers (n = 12). Interviewed women participated in two focus group discussions (n = 15). Interviews were transcribed verbatim and analyzed using Atlas.ti software, based on Gale et al.'s framework approach. Findings informed three stakeholder dialogues in which women as well as healthcare providers and policymakers from various territorial levels participated. Results: Our methodological approach succeeded in integrating women's perspectives-from initial data collection in interviews to identify issues, focus group discussions to increase rigor, and stakeholder dialogues to develop tailored recommendations based on PREs. Discussion: This is one of the first studies in Switzerland that used PREs to research healthcare services and healthcare needs among immigrant women with chronic illnesses. This paper provides new insights on how to better understand existing challenges and potentially improve access to and quality of care.}, } @article {pmid33192035, year = {2021}, author = {Sullivan, FR}, title = {Critical pedagogy and teacher professional development for online and blended learning: the equity imperative in the shift to digital.}, journal = {Educational technology research and development : ETR & D}, volume = {69}, number = {1}, pages = {21-24}, pmid = {33192035}, issn = {1042-1629}, abstract = {This paper provides a response to the work of Philipsen et al. (Educ Technol Res Dev 67:1145-1174, Philipsen et al., Educational Technology, Research and Development 67:1145-1174, 2019), from a critical pedagogy perspective. Here, critical pedagogy is defined from a post-colonial framework focused on liberation. From this perspective, the value of Philipsen et al.'s paper is in its implicit alignment with critical methodologies, including how liberatory ideas are embedded in the TPD for OBL framework. In a response to Philipsen et al.'s work, this paper provides advice on practical actions teachers can take to develop their ability to engage in critical pedagogy, both from the TPD for OBL lens and from an equity lens. This paper concludes with a discussion of the limitations of the meta-aggregative review, including the lack of an explicitly critical framework, and it provides suggestions for how the work could be improved, especially as regards a discussion of equity for teachers and students. Future research in this area should focus on methods for disrupting educational inequity regarding online and blended learning.}, } @article {pmid33187520, year = {2020}, author = {Gesicho, MB and Were, MC and Babic, A}, title = {Data cleaning process for HIV-indicator data extracted from DHIS2 national reporting system: a case study of Kenya.}, journal = {BMC medical informatics and decision making}, volume = {20}, number = {1}, pages = {293}, pmid = {33187520}, issn = {1472-6947}, support = {QZA-0484//Direktoratet for Utviklingssamarbeid/International ; }, mesh = {*Data Accuracy ; *HIV Infections/epidemiology/prevention & control ; *Health Information Systems ; Humans ; Kenya ; Software ; }, abstract = {BACKGROUND: The District Health Information Software-2 (DHIS2) is widely used by countries for national-level aggregate reporting of health-data. To best leverage DHIS2 data for decision-making, countries need to ensure that data within their systems are of the highest quality. Comprehensive, systematic, and transparent data cleaning approaches form a core component of preparing DHIS2 data for analyses. Unfortunately, there is paucity of exhaustive and systematic descriptions of data cleaning processes employed on DHIS2-based data. The aim of this study was to report on methods and results of a systematic and replicable data cleaning approach applied on HIV-data gathered within DHIS2 from 2011 to 2018 in Kenya, for secondary analyses.

METHODS: Six programmatic area reports containing HIV-indicators were extracted from DHIS2 for all care facilities in all counties in Kenya from 2011 to 2018. Data variables extracted included reporting rate, reporting timeliness, and HIV-indicator data elements per facility per year. 93,179 facility-records from 11,446 health facilities were extracted from year 2011 to 2018. Van den Broeck et al.'s framework, involving repeated cycles of a three-phase process (data screening, data diagnosis and data treatment), was employed semi-automatically within a generic five-step data-cleaning sequence, which was developed and applied in cleaning the extracted data. Various quality issues were identified, and Friedman analysis of variance conducted to examine differences in distribution of records with selected issues across eight years.

RESULTS: Facility-records with no data accounted for 50.23% and were removed. Of the remaining, 0.03% had over 100% in reporting rates. Of facility-records with reporting data, 0.66% and 0.46% were retained for voluntary medical male circumcision and blood safety programmatic area reports respectively, given that few facilities submitted data or offered these services. Distribution of facility-records with selected quality issues varied significantly by programmatic area (p < 0.001). The final clean dataset obtained was suitable to be used for subsequent secondary analyses.

CONCLUSIONS: Comprehensive, systematic, and transparent reporting of cleaning-process is important for validity of the research studies as well as data utilization. The semi-automatic procedures used resulted in improved data quality for use in secondary analyses, which could not be secured by automated procedures solemnly.}, } @article {pmid33176898, year = {2021}, author = {Medina, LD and Torres, S and Gioia, A and Ochoa Lopez, A and Wang, J and Cirino, PT}, title = {Reporting of Demographic Variables in Neuropsychological Research: An Update of O'Bryant et al.'s Trends in the Current Literature.}, journal = {Journal of the International Neuropsychological Society : JINS}, volume = {27}, number = {5}, pages = {497-507}, doi = {10.1017/S1355617720001083}, pmid = {33176898}, issn = {1469-7661}, mesh = {Adult ; Child ; Demography ; Educational Status ; Humans ; *Neuropsychology ; *Social Class ; }, abstract = {OBJECTIVE: Demographic trends and the globalization of neuropsychology have led to a push toward inclusivity and diversity in neuropsychological research in order to maintain relevance in the healthcare marketplace. However, in a review of neuropsychological journals, O'Bryant et al. found systematic under-reporting of sample characteristics vital for understanding the generalizability of research findings. We sought to update and expand the findings reported by O'Bryant et al.

METHOD: We evaluated 1648 journal articles published between 2016 and 2019 from 7 neuropsychological journals. Of these, 1277 were original research or secondary analyses and were examined further. Articles were coded for reporting of age, sex/gender, years of education, ethnicity/race, socioeconomic status (SES), language, and acculturation. Additionally, we recorded information related to sample size, country, and whether the article focused on a pediatric or adult sample.

RESULTS: Key variables such as age and sex/gender (both over 95%) as well as education (71%) were frequently reported. Language (20%) and race/ethnicity (36%) were modestly reported, and SES (13%), and acculturation (<1%) were more rarely reported. SES was more commonly reported in pediatric than adult samples, and the opposite was true for education. There were differences between the present results and those of O'Bryant et al., though the same general trends remained.

CONCLUSIONS: Reporting of demographic data in neuropsychological research appears to be slowly changing toward greater comprehensiveness, though clearly more work is needed. Greater systematic reporting of such data is likely to be beneficial for the generalizability and contextualization of neurocognitive function.}, } @article {pmid33176562, year = {2021}, author = {Rosenthal, D}, title = {Assessing criteria for theories.}, journal = {Cognitive neuroscience}, volume = {12}, number = {2}, pages = {84-85}, doi = {10.1080/17588928.2020.1838471}, pmid = {33176562}, issn = {1758-8936}, mesh = {*Consciousness ; Humans ; *Models, Neurological ; }, abstract = {I raise concerns about Doerig et al.'s general project, about three of their criteria, and about their treatment of higher-order-thought theory.}, } @article {pmid33173884, year = {2020}, author = {Xiao, M and Chen, Y and Cole, SR and MacLehose, R and Richardson, D and Chu, H}, title = {Is OR "portable" in meta-analysis? Time to consider bivariate generalized linear mixed model.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, doi = {10.1101/2020.11.05.20226811}, pmid = {33173884}, abstract = {OBJECTIVES: A recent paper by Doi et al. advocated completely replacing the relative risk (RR) with the odds ratio (OR) as the effect measure used to report the association between a treatment and a binary outcome in clinical trials and meta-analyses. Besides some practical advantages of RR over OR and the well-known issue of the OR being non-collapsible, Doi et al.'s key assumption that the OR is "portable" in the meta-analysis, i.e., study-specific ORs are likely not correlated with baseline risks, was not well justified. Study designs and settings: We summarized the Spearman's rank correlation coefficient between study-specific OR and the baseline risk in 40,243 meta-analyses from the Cochrane Database of Systematic Reviews (CDSR).

RESULTS: Study-specific ORs are negatively correlated with baseline risk of disease (i.e., higher ORs tend to be observed in studies with lower baseline risks of disease) for most meta-analyses in CDSR. Using a meta-analysis comparing the effect of oral sumatriptan (100 mg) versus placebo on mitigating the acute headache at 2 hours after drug administration, we demonstrate that there is a strong negative correlation between OR (RR or RD) with the baseline risk and the conditional effects notably vary with baseline risks.

CONCLUSIONS: Replacing RR or RD with OR is currently unadvisable in clinical trials and meta-analyses. It is possible that no effect measure is "portable" in a meta-analysis. In cases where portability of the effect measure is challenging to satisfy, we suggest presenting the conditional effect based on the baseline risk using a bivariate generalized linear mixed model. The bivariate generalized linear mixed model can be used to account for correlation between the effect measure and baseline disease risk. Furthermore, in addition to the overall (or marginal) effect, we recommend that investigators also report the effects conditioning on the baseline risk.}, } @article {pmid33168553, year = {2020}, author = {Ryan, N and Dike, L and Ojo, T and Vieira, D and Nnodu, O and Gyamfi, J and Peprah, E}, title = {Implementation of the therapeutic use of hydroxyurea for sickle cell disease management in resource-constrained settings: a systematic review of adoption, cost and acceptability.}, journal = {BMJ open}, volume = {10}, number = {11}, pages = {e038685}, pmid = {33168553}, issn = {2044-6055}, mesh = {*Anemia, Sickle Cell/drug therapy ; Cohort Studies ; Cross-Sectional Studies ; Humans ; *Hydroxyurea/therapeutic use ; Jamaica ; Nigeria ; }, abstract = {OBJECTIVES: Mortality associated with sickle cell disease (SCD) is high in many low- and middle-income countries (LMICs). Hydroxyurea, a medicine to effectively manage SCD, is not widely available in resource-constrained settings. We identified and synthesised the reported implementation outcomes for the therapeutic use of hydroxyurea for SCD in these settings.

DESIGN: Systematic review.

DATA SOURCES: PubMed, Embase, Cochrane, Web of Science Plus, Global Health, CINAHL, and PsycINFO were searched February through May 2019 without any restrictions on publication date.

ELIGIBILITY CRITERIA: We included empirical studies of hydroxyurea for management of SCD that were carried out in LMICs and reported on implementation outcomes.

DATA EXTRACTION AND SYNTHESIS: Two reviewers independently assessed studies for inclusion, carried out data extraction using Proctor et al.'s implementation and health service outcomes, and assessed the risk of bias using ROBINS-I (Risk Of Bias In Non-randomised Studies - of Interventions).

RESULTS: Two cross-sectional surveys (n=2) and one cohort study (n=1) reported implementation of hydroxyurea for SCD management, namely regarding outcomes of adoption (n=3), cost (n=3) and acceptability (n=1). These studies were conducted exclusively among paediatric and adults populations in clinical settings in Nigeria (n=2) or Jamaica (n=1). Adoption is low, as observed through reported provider practices and patient adherence, in part shaped by misinformation and fear of side effects among patients, provider beliefs regarding affordability and organisational challenges with procuring the medicine. There was no difference in the cost of hydroxyurea therapy compared with blood transfusion in the paediatric population in urban Jamaica. Risk of bias was low or moderate across the included studies.

CONCLUSIONS: This review rigorously and systematically assessed the evidence on implementation of hydroxyurea in resource-constrained settings such as LMICs. Findings suggest that knowledge regarding implementation is low. To address the know-do gap and guide clinical practice, implementation research is needed. Integrating effective interventions into existing health systems to improve hydroxyurea uptake is essential to reducing SCD-associated mortality.

PROSPERO REGISTRATION NUMBER: CRD42020155953.}, } @article {pmid33141114, year = {2020}, author = {Kuss, DJ}, title = {Risk reduction and harm prevention in technology use. •.}, journal = {Journal of behavioral addictions}, volume = {9}, number = {4}, pages = {895-897}, pmid = {33141114}, issn = {2063-5303}, mesh = {Humans ; *Risk Reduction Behavior ; *Technology ; }, abstract = {This commentary paper draws on Swanton et al.'s (2020) paper "Problematic risk-taking involving emerging technologies: A stakeholder framework to minimize harms" to discuss issues pertaining to the challenges and possible risks emerging technologies may pose for the users. It acknowledges technology use is not problematic per se, but for some users, it can be associated with preventable harms. Corporate social responsibility is called for to protect consumers. It is argued that there exists a collective responsibility to ensure technology can be used in a healthy and beneficial way, risk is reduced and harm is prevented.}, } @article {pmid33140229, year = {2021}, author = {McKenzie, CRM and Leong, LM and Sher, S}, title = {Default sensitivity in attempts at social influence.}, journal = {Psychonomic bulletin & review}, volume = {28}, number = {2}, pages = {695-702}, pmid = {33140229}, issn = {1531-5320}, support = {Scholar Award//James S. McDonnell Foundation/ ; }, mesh = {Adult ; *Choice Behavior ; Female ; *Goals ; Humans ; Male ; *Social Behavior ; }, abstract = {While past research has demonstrated the power of defaults to nudge decision makers toward desired outcomes, few studies have examined whether people understand how to strategically set defaults to influence others' choices. A recent paper (Zlatev et al. Proceedings of the National Academy of Sciences, 114, 13643-13648, 2017) found that participants exhibited "default neglect," or the failure to set optimal defaults at better than chance levels. However, we show that this poor performance is specific to the complex and potentially confusing paradigms they used, and does not reflect a general lack of understanding regarding defaults. Using simple scenarios, Experiments 1A and 1B provide clear evidence that people can optimally set defaults given their goals. In Experiment 2, we conducted a direct and conceptual replication of one of Zlatev et al.'s original studies, which found that participants selected the optimal default significantly less than chance. While our direct replication found results similar to those in the original study, our conceptual replication, which simplified the task, instead found the opposite. Experiment 3 manipulated the framing of the option attributes, which were confounded with the default in the original study, and found that the original framing led to below-chance performance while the alternate framing led to above-chance performance. Together, our results cast doubt on the prevalence and generalizability of default neglect, and instead suggest that people are capable of setting optimal defaults in attempts at social influence.}, } @article {pmid33128220, year = {2021}, author = {Zarzycka, B and Krok, D}, title = {Disclosure to God as a Mediator Between Private Prayer and Psychological Well-Being in a Christian Sample.}, journal = {Journal of religion and health}, volume = {60}, number = {2}, pages = {1083-1095}, pmid = {33128220}, issn = {1573-6571}, mesh = {Adolescent ; Adult ; Black or African American ; *Christianity ; *Disclosure ; Female ; Humans ; Mental Health ; Middle Aged ; Young Adult ; }, abstract = {Although a number of studies have reported the psychological and physical benefits of prayer, only a few have examined the means by which prayer affects health. Winkeljohn Black et al. (J Relig Health 54(2):540-553, 2015. https://doi.org/10.1007/s10943-014-9840-4) found disclosure to God as a mediator in the relationship between prayer and mental health. In their study, the authors used Poloma and Pendleton's (Rev Relig Res 31(1):46-53, 1989. https://doi.org/10.2307/3511023,) model of prayer. This study examined whether disclosure to God as a mediator can be upheld with Laird et al.'s (Int J Psychol Relig 14(4):251-272, 2004) prayer model. The study included 285 Polish adults (50.2% of women), aged between 18 and 60 years. The Multidimensional Prayer Inventory, the Revised Distress Disclosure Index, and the Psychological Well-Being Scale were applied to the research. The results showed that the prayer of thanksgiving correlated positively and the prayer of supplication negatively with well-being. Two indirect effects were significant, indicating disclosure to God as a mediator of the confession-well-being link and the supplication-well-being link.}, } @article {pmid33124226, year = {2020}, author = {Li, XM and Mu, L and Tian, M and Zheng, LR and Li, YY}, title = {[Characteristics, Sources, and Health Risks of Elements in PM2.5 in Shanxi University Town].}, journal = {Huan jing ke xue= Huanjing kexue}, volume = {41}, number = {11}, pages = {4825-4831}, doi = {10.13227/j.hjkx.202003011}, pmid = {33124226}, issn = {0250-3301}, mesh = {Adult ; *Air Pollutants/analysis ; Child ; China ; Cities ; Dust/analysis ; Environmental Monitoring ; Female ; Humans ; Male ; *Particulate Matter/analysis ; Risk Assessment ; Seasons ; Universities ; }, abstract = {In order to investigate the pollution characteristics and sources of elements in PM2.5 in the Shanxi University Town in 2017, an energy dispersive X-ray fluorescence spectrometer (ED-XRF) was used to analyze 21 kinds of elements in PM2.5 samples. A health risk assessment was conducted for Mn, Zn, Cu, Sb, Pb, Cr, Co, and Ni. The main sources of elements were identified by the principal component analysis (PCA) and positive matrix factorization (PMF). The results found that, among the 21 kinds of elements in PM2.5 in Shanxi University Town, the mass concentration of Ca was the highest, followed by Si, Fe, Al, S, K, and Cl. These seven elements accounted for 95.71% of the total element concentrations. The concentration of Cr exceeded the annual average concentration limit of ambient air quality standards in China by 104 times. The concentration of Ca in PM2.5 was the highest in spring, summer, and winter, while in autumn the concentration of S was the highest. Mn was the element that had non-carcinogenic risks to the three population types, and the level of risks were in the order of children > adult men > adult women. Cr and Co had tolerable carcinogenic risks, and the risk levels were in the order of adult men > adult women > children. The main sources of elements in PM2.5 in Shanxi University Town in 2017 were natural mineral dust, urban dust, coal combustion, and traffic.}, } @article {pmid33117207, year = {2020}, author = {Ogihara, Y}, title = {Unique Names in China: Insights From Research in Japan-Commentary: Increasing Need for Uniqueness in Contemporary China: Empirical Evidence.}, journal = {Frontiers in psychology}, volume = {11}, number = {}, pages = {2136}, pmid = {33117207}, issn = {1664-1078}, abstract = {By comparing naming practices between China and Japan, I propose three suggestions on Cai et al.'s (2018) Study 2, which examined historical changes in baby names in China. Their study found that the average daily frequencies of Chinese characters used in baby names decreased between 1950 and 2009. The authors concluded that unique names increased for this period and suggested a rise in the need for uniqueness and individualism in China. However, there are three questions that have remained unanswered. First, did the Chinese characters that were used in names indeed become more unique over time? Second, did the number of Chinese characters in names increase over time? Third, did the reading (pronunciation) of names become more unique over time? Answering these three questions would further increase the validity and impacts of the article and contribute to a better understanding of cultural changes in China.}, } @article {pmid33097084, year = {2020}, author = {Williams, MT and Skinta, MD and Kanter, JW and Martin-Willett, R and Mier-Chairez, J and Debreaux, M and Rosen, DC}, title = {A qualitative study of microaggressions against African Americans on predominantly White campuses.}, journal = {BMC psychology}, volume = {8}, number = {1}, pages = {111}, pmid = {33097084}, issn = {2050-7283}, support = {Visionary Grant//American Psychological Foundation/ ; 950-232127//Institute of Neurosciences, Mental Health and Addiction/ ; }, mesh = {Black or African American/*psychology ; *Aggression ; Female ; Humans ; Male ; *Qualitative Research ; Racism/*statistics & numerical data ; *Universities ; White People/*psychology ; Young Adult ; }, abstract = {BACKGROUND: Pierce's (The Black seventies: an extending horizon book, 1970) conception of "subtle and stunning" daily racial offenses, or microaggressions, remains salient even 50 years after it was introduced. Microaggressions were defined further by Sue and colleagues (Am Psychol 62:271, 2007), and this construct has found growing utility as the deleterious effects of microaggressions on the health of people of color continues to mount. Microaggressions are common on campuses and contribute to negative social, academic, and mental health outcomes.

METHOD: This paper explores how Black college students' experiences correspond to or differ from the microaggression types originally proposed by Sue et al. (Am Psychol 62:271, 2007). Themes were identified from focus group data of students of color (N = 36) from predominately White institutions (PWIs) of higher learning (N = 3) using interpretative phenomenological analysis.

RESULTS: We identified 15 categories of racial microaggressions, largely consistent with the original taxonomy of Sue et al. but expanded in several notable ways. New categories in our data and observed by other researchers, included categories termed Connecting via Stereotypes, Exoticization and Eroticization, and Avoidance and Distancing. Lesser studied categories identified included Sue et al.'s Denial of Individual Racism, and new categories termed Reverse Racism Hostility, Connecting via Stereotypes, and Environmental Attacks.

DISCUSSION: While previous literature has either embraced the taxonomy developed by Sue and colleagues or proposed a novel taxonomy, this study synthesized the Sue framework in concert with our own focus group findings and the contributions of other researchers. Improving our understanding of microaggressions as they impact people of color may better allow for improved understanding and measurement of this important construct.}, } @article {pmid33095158, year = {2020}, author = {Greenhalgh, R and Dermauw, W and Glas, JJ and Rombauts, S and Wybouw, N and Thomas, J and Alba, JM and Pritham, EJ and Legarrea, S and Feyereisen, R and Van de Peer, Y and Van Leeuwen, T and Clark, RM and Kant, MR}, title = {Genome streamlining in a minute herbivore that manipulates its host plant.}, journal = {eLife}, volume = {9}, number = {}, pages = {}, pmid = {33095158}, issn = {2050-084X}, support = {773902-SuperPests//Horizon 2020 - Research and Innovation Framework Programme/International ; STW-GAP/13550//Netherlands Organisation for Scientific Research/International ; 12T9818N//Research Foundation Flanders/International ; 772026-POLYADAPT//European Union Horizon 2020 research and innovation program/International ; 1457346//USA National Science Foundation/International ; 1274917N//Research Foundation Flanders/International ; 1457346//National Science Foundation/International ; T32 GM007464/GM/NIGMS NIH HHS/United States ; STW-VIDI/13492//Netherlands Organisation for Scientific Research/International ; 773902-SuperPests//European Union Horizon 2020 research and innovation program/International ; }, mesh = {Animals ; Evolution, Molecular ; *Genome ; *Herbivory ; Host-Pathogen Interactions ; Solanum lycopersicum/*parasitology ; Mites/*genetics ; Phylogeny ; }, abstract = {The tomato russet mite, Aculops lycopersici, is among the smallest animals on earth. It is a worldwide pest on tomato and can potently suppress the host's natural resistance. We sequenced its genome, the first of an eriophyoid, and explored whether there are genomic features associated with the mite's minute size and lifestyle. At only 32.5 Mb, the genome is the smallest yet reported for any arthropod and, reminiscent of microbial eukaryotes, exceptionally streamlined. It has few transposable elements, tiny intergenic regions, and is remarkably intron-poor, as more than 80% of coding genes are intronless. Furthermore, in accordance with ecological specialization theory, this defense-suppressing herbivore has extremely reduced environmental response gene families such as those involved in chemoreception and detoxification. Other losses associate with this species' highly derived body plan. Our findings accelerate the understanding of evolutionary forces underpinning metazoan life at the limits of small physical and genome size.}, } @article {pmid33084039, year = {2021}, author = {Kranak, MP and Falligant, JM and Hausman, NL}, title = {Application of automated nonparametric statistical analysis in clinical contexts.}, journal = {Journal of applied behavior analysis}, volume = {54}, number = {2}, pages = {824-833}, doi = {10.1002/jaba.789}, pmid = {33084039}, issn = {1938-3703}, mesh = {*Behavior Therapy ; Humans ; Reproducibility of Results ; *Research Design ; }, abstract = {Functional analyses (FAs) provide clinicians with results upon which they design behavioral treatments. Unfortunately, interrater reliability of visual analysis of FA results can be inconsistent. Accordingly, researchers have designed quantitative metrics and visual aids to supplement visual analysis. Recently, Hall et al. (2020) provided a proof of concept for using automated nonparametric statistical analysis (ANSA) to interpret FA data. Their results show promise for ANSA as a supplemental tool. However, they evaluated ANSA with only published FA datasets, which may not be representative of FAs commonly encountered in clinical care. Therefore, the purpose of this replication was to compare ANSA to another validated supplemental aid (i.e., the structured criteria method) and investigate its utility with unpublished clinical FA data. Our results were consistent with Hall et al.'s, indicating ANSA may augment clinical interpretation of FA data. Recommendations for clinical applications of ANSA and future directions for researchers are discussed.}, } @article {pmid33083848, year = {2020}, author = {Schmitt, MH and Shrader, AM and Ward, D}, title = {Megaherbivore browsers vs. tannins: is being big enough?.}, journal = {Oecologia}, volume = {194}, number = {3}, pages = {383-390}, doi = {10.1007/s00442-020-04784-9}, pmid = {33083848}, issn = {1432-1939}, support = {90448, 97262//National Research Foundation (RSA)/ ; }, mesh = {Animals ; Diet ; Perissodactyla ; Saliva ; *Salivary Proteins and Peptides ; *Tannins ; }, abstract = {Megaherbivores have been of particular interest to scientists because of the physiological and ecological challenges associated with their extreme body size. Yet, one question that has seldom been explored is how browsing megaherbivores cope with plant secondary metabolites (PSMs), such as tannins, found in their food. It is possible that the sheer body size of these megaherbivores allows them to ingest tannins with no deleterious effects. However, it is plausible that megaherbivores must rely on other mechanisms to cope with PSMs, such as the production of salivary tannin-binding proteins. Thus, we aimed to determine whether megaherbivore browsers produce tannin-binding proteins to further reduce the consequences of ingesting a tannin-rich diet. Using a series of laboratory assays, we explored whether elephants, black rhinoceros, and giraffe had tannin-binding proteins in their saliva. We tested for the presence of proline-rich proteins in the saliva using two different approaches: (1) SDS-PAGE using Laemmli's (Laemmli, Nature 227:680-685, 1970) destaining method, and (2) comparative SDS-PAGE gels using Beeley et al.'s (Beeley et al. Electrophoresis 12:493-499, 1991) method for staining and destaining to probe for proline-rich proteins. Then, to test for the tannin-binding affinity of their saliva, we performed an inhibition assay. We did not observe proline-rich proteins in any of the megaherbivore species, but they did have other protein(s) in their saliva that have a high tannin-binding affinity. Our results highlight that, despite their large body sizes, and their abilities to tolerate low-quality food, browsing megaherbivores have likely evolved tannin-binding proteins as a way of coping with the negative effects of tannins.}, } @article {pmid33075356, year = {2021}, author = {Sompornpailin, D and Ratanatawanate, C and Chantanavorakunchai, N and Punyapalakul, P}, title = {Effects of electrolytes and fractionated dissolved organic matter on selective adsorption of pharmaceuticals on terephthalic acid-based metal-organic frameworks.}, journal = {Environmental research}, volume = {196}, number = {}, pages = {110335}, doi = {10.1016/j.envres.2020.110335}, pmid = {33075356}, issn = {1096-0953}, mesh = {Adsorption ; *Metal-Organic Frameworks ; *Pharmaceutical Preparations ; *Phthalic Acids ; }, abstract = {In this study, we investigated the synergetic effects of coexisting electrolytes and dissolved organic matter (DOM) on Carbamazepine (CBZ) and Ciprofloxacin (CIP) adsorption on the 1D flexible structure of MIL-53(Al) and 3D rigid structure of UiO-66(Zr). The effects of electrolytes on the adsorption of CBZ and CIP on 1D flexible framework of MIL-53(Al) were more significant than those observed from the 3D framework of UiO-66(Zr). The presence of sulfate, nitrate, and phosphate anions indicates high potential to promote the adsorption of CBZ and CIP onto MIL-53(Al) and UiO-66(Zr) because of the decrease of solubility and strengthening of electrostatic interactions by substitution of oxo-anions at the metal complex node via covalent bonding. The lower hydration energy of the potassium ion enhanced CBZ adsorption on MIL-53(Al), while the higher hydration energy of calcium and magnesium ions reduced the adsorption capacity of CBZ and CIP on MIL-53(Al) and UiO-66(Zr). CBZ interacted with fractionated humic acid better than CIP. High-density carboxylic and aromatic functional groups on humic acid ensured that only humic acid larger than 1KDa was adsorbed by MIL-53(Al). Tryptophan-like and humic acid-like DOM were both detected in real hospital effluent, and their effects on CIP and CBZ adsorption onto MIL-53(Al) were investigated. The presence of tryptophan did not affect CBZ adsorption on MIL-53(Al) (except when coexisting with calcium ions). Conversely, tryptophan interfered with CIP adsorption. The presence of humic acid lower than 1KDa promoted the adsorption of CBZ and CIP by increasing the breathing effect of MIL-53(Al)'s 1D flexible framework. The presence of humic acid with molecular size greater than 1KDa enhanced both CBZ and CIP adsorption via a multilayer adsorption mechanism.}, } @article {pmid33073762, year = {2020}, author = {Marrero, RJ and Fumero, A and González-Villalobos, JA and Hernández-Cabrera, JA and Fonseca-Pedrero, E}, title = {Psychometric Properties of the Schizotypal Personality Questionnaire (SPQ) in a Mexican Population: Invariance Across Gender and Age.}, journal = {Psicothema}, volume = {32}, number = {4}, pages = {559-566}, doi = {10.7334/psicothema2020.216}, pmid = {33073762}, issn = {1886-144X}, mesh = {Adult ; Factor Analysis, Statistical ; Female ; Humans ; Personality ; Psychometrics ; Reproducibility of Results ; *Schizotypal Personality Disorder/diagnosis ; Surveys and Questionnaires ; }, abstract = {BACKGROUND: The present study tested the factorial structure of the Schizotypal Personality Questionnaire (SPQ) in Mexican adults. Although this instrument has been validated in different cultural contexts, there are no studies to date that analyze its psychometric properties in a Mexican sample.

METHOD: 307 adults completed the SPQ, seven participants were removed for being at high risk of psychosis. The final sample was made up of 300 participants (M = 34.58, SD = 13.77), of whom 62.8% were female. Raine's three-factor model and Stefanis et al.'s four-factor model were tested.

RESULTS: The results indicated that both factor structures had a good fit to the data. However, the best evidence was for the three-factor solution. Configural, metric, and scalar invariance according to gender and age for the three-factor model was displayed. Further analyses showed women scored slightly higher in excessive social anxiety but this result was not statistically significant. Younger participants had higher scores on ideas of reference, excessive social anxiety, no close friends, and odd speech than the older group.

CONCLUSIONS: These findings provide support for the use of the SPQ in the Mexican population.}, } @article {pmid33071846, year = {2020}, author = {Jiang, F and Lu, S and Jiang, T and Jia, H}, title = {Does the Relation Between Humor Styles and Subjective Well-Being Vary Across Culture and Age? A Meta-Analysis.}, journal = {Frontiers in psychology}, volume = {11}, number = {}, pages = {2213}, pmid = {33071846}, issn = {1664-1078}, abstract = {An earlier review (Schneider et al., 2018) examined the connection between humor styles and mental health. The present article supplements and extends Schneider et al.'s review by surveying a broader concept, subjective well-being (SWB), and investigating the moderating effects of culture and age. To this end, we collected data from 85 studies, with 27,562 participants of varying ages and cultures. Meta-analysis results indicate that affiliative and self-enhancing humor enhances SWB, whereas aggressive and self-defeating humor damages SWB. Culture and age do not moderate the relation between humor styles and SWB. We discuss implications for better understanding of the relationships among culture, age, humor, and SWB.}, } @article {pmid33068483, year = {2021}, author = {Xia, S and Song, Z and Li, Q and Guo, L and Yu, C and Singh, BP and Fu, X and Chen, C and Wang, Y and Wang, H}, title = {Distribution, sources, and decomposition of soil organic matter along a salinity gradient in estuarine wetlands characterized by C:N ratio, δ[13] C-δ[15] N, and lignin biomarker.}, journal = {Global change biology}, volume = {27}, number = {2}, pages = {417-434}, doi = {10.1111/gcb.15403}, pmid = {33068483}, issn = {1365-2486}, support = {41930862//National Natural Science Foundation of China/ ; 41571130042//National Natural Science Foundation of China/ ; 41522207//National Natural Science Foundation of China/ ; 2016YFA0601002//State's Key Project of Research and Development Plan of China/ ; 2017YFC0212700//State's Key Project of Research and Development Plan of China/ ; }, mesh = {Biomarkers ; Carbon/analysis ; China ; Lignin ; Salinity ; *Soil ; *Wetlands ; }, abstract = {Despite increasing recognition of the critical role of coastal wetlands in mitigating climate change, sea-level rise, and salinity increase, soil organic carbon (SOC) sequestration mechanisms in estuarine wetlands remain poorly understood. Here, we present new results on the source, decomposition, and storage of SOC in estuarine wetlands with four vegetation types, including single Phragmites australis (P, habitat I), a mixture of P. australis and Suaeda salsa (P + S, habitat II), single S. salsa (S, habitat III), and tidal flat (TF, habitat IV) across a salinity gradient. Values of δ[13] C increased with depth in aerobic soil layers (0-40 cm) but slightly decreased in anaerobic soil layers (40-100 cm). The δ[15] N was significantly enriched in soil organic matter at all depths than in the living plant tissues, indicating a preferential decomposition of [14] N-enriched organic components. Thus, the kinetic isotope fractionation during microbial degradation and the preferential substrate utilization are the dominant mechanisms in regulating isotopic compositions in aerobic and anaerobic conditions, respectively. Stable isotopic (δ[13] C and δ[15] N), elemental (C and N), and lignin composition (inherited (Ad/Al)s and C/V) were not completely consistent in reflecting the differences in SOC decomposition or accumulation among four vegetation types, possibly due to differences in litter inputs, root distributions, substrate quality, water-table level, salinity, and microbial community composition/activity. Organic C contents and storage decreased from upstream to downstream, likely due to primarily changes in autochthonous sources (e.g., decreased onsite plant biomass input) and allochthonous materials (e.g., decreased fluvially transported upland river inputs, and increased tidally induced marine algae and phytoplankton). Our results revealed that multiple indicators are essential to unravel the degree of SOC decomposition and accumulation, and a combination of C:N ratios, δ[13] C, δ[15] N, and lignin biomarker provides a robust approach to decipher the decomposition and source of sedimentary organic matter along the river-estuary-ocean continuum.}, } @article {pmid33059932, year = {2020}, author = {Zhao, C and Egger, H}, title = {Cognitive impact of early separation from migrant parents: A spectrum of risk and key mechanisms in child development contexts. A commentary on Hou et al., (2020).}, journal = {Social science & medicine (1982)}, volume = {266}, number = {}, pages = {113427}, doi = {10.1016/j.socscimed.2020.113427}, pmid = {33059932}, issn = {1873-5347}, mesh = {Adolescent ; Child ; Child Development ; Child, Preschool ; China ; Cognition ; Humans ; Parents ; *Transients and Migrants ; }, abstract = {Prolonged separation from migrant parents may lead to child development risks, despite the potential benefits from improved financial circumstances. Within the substantial literature on the health and well-being of the so-called left-behind children, the cognitive impact of parental migration has been inconclusive across different settings globally. In this issue, Hou et al.'s study in rural China focused on school-age children who experience persistent absence of both migrant parents since infancy, and revealed disadvantages in language comprehension outcomes among these children, despite the mitigating effect of higher household income. While results from this study are limited to the ongoing parent-child separation, previous absence of migrant parents has been suggested to have long-lasting negative effects in studies of adolescents in reunited families. Findings from Hou and colleagues' study highlight the needs to better understand migration-related parent-child separation during sensitive developmental periods in infancy and early childhood. A spectrum of risk due to parental migration should be established, accounting for the timing and duration of migration and care arrangements, in order to better identify the at-risk children in communities affected by out-migration. Future research should further explore the mediating and moderating factors in child's environments, and evaluate post-separation adjustment among reunited families after parents' return migration. Research evidence on these aspects will inform the development of tailored intervention programs for left-behind children, and strengthen the abilities of families and communities in best serving the needs of children affected by prolonged parental absence.}, } @article {pmid33058346, year = {2020}, author = {Stevison, LS and McGaugh, SE}, title = {It's time to stop sweeping recombination rate under the genome scan rug.}, journal = {Molecular ecology}, volume = {29}, number = {22}, pages = {4249-4253}, doi = {10.1111/mec.15690}, pmid = {33058346}, issn = {1365-294X}, mesh = {*Genome ; Genomics ; Hybridization, Genetic ; Recombination, Genetic ; *Selection, Genetic ; }, abstract = {Different parts of the genome can vary widely in their evolutionary histories and sequence divergence from other species. Indeed, some of the most interesting biology (e.g., hybridization, horizontal gene transfer, variable mutation rates across the genome) is revealed by the discordant relationships between taxa across the genome. The goal for much of evolutionary genetics is centred on understanding the evolutionary processes by which such varied signatures arise and are maintained. Many evolutionary genetics studies seek to identify signatures of positive selection between two closely related ecotypes or taxa by delineating regions with particularly high divergence relative to a genome-wide average, often termed "divergence outliers." In a From the Cover article in this issue of Molecular Ecology, Booker et al. take a major step forward in showing that recombination rate differences are sufficient to create false positive divergence outliers, even under neutrality. They demonstrate that the variance of genome scan metrics is especially high in regions with low recombination rates, consistent with previous work. Furthermore, they show that both relative and absolute measures of divergence (FST and DXY , respectively) as well as other commonly used statistics in genome scans (e.g., πW , Tajima's D and H12) all have similar covariance between variance and local recombination rate. Finally, Booker et al. show that low recombination regions will tend to produce more outliers if genome-wide averages are used as cut-offs to define genomic outliers. Booker et al.'s results suggest that recombination rate variation, even under neutral conditions, can shape genome scans for selection, and this important variable can no longer be ignored.}, } @article {pmid33052858, year = {2021}, author = {LYi, S and Jo, J and Seo, J}, title = {Comparative Layouts Revisited: Design Space, Guidelines, and Future Directions.}, journal = {IEEE transactions on visualization and computer graphics}, volume = {27}, number = {2}, pages = {1525-1535}, doi = {10.1109/TVCG.2020.3030419}, pmid = {33052858}, issn = {1941-0506}, abstract = {We present a systematic review on three comparative layouts-juxtaposition, superposition, and explicit-encoding-which are information visualization (InfoVis) layouts designed to support comparison tasks. For the last decade, these layouts have served as fundamental idioms in designing many visualization systems. However, we found that the layouts have been used with inconsistent terms and confusion, and the lessons from previous studies are fragmented. The goal of our research is to distill the results from previous studies into a consistent and reusable framework. We review 127 research papers, including 15 papers with quantitative user studies, which employed comparative layouts. We first alleviate the ambiguous boundaries in the design space of comparative layouts by suggesting lucid terminology (e.g., chart-wise and item-wise juxtaposition). We then identify the diverse aspects of comparative layouts, such as the advantages and concerns of using each layout in the real-world scenarios and researchers' approaches to overcome the concerns. Building our knowledge on top of the initial insights gained from the Gleicher et al.'s survey [19], we elaborate on relevant empirical evidence that we distilled from our survey (e.g., the actual effectiveness of the layouts in different study settings) and identify novel facets that the original work did not cover (e.g., the familiarity of the layouts to people). Finally, we show the consistent and contradictory results on the performance of comparative layouts and offer practical implications for using the layouts by suggesting trade-offs and seven actionable guidelines.}, } @article {pmid33052183, year = {2021}, author = {Abaci, S and Robertson, J and Linklater, H and McNeill, F}, title = {Supporting school teachers' rapid engagement with online education.}, journal = {Educational technology research and development : ETR & D}, volume = {69}, number = {1}, pages = {29-34}, pmid = {33052183}, issn = {1042-1629}, abstract = {In response to Philipsen et al.'s (Educ Technol Res Dev 67:1145-1174, 2019) article titled "Improving teacher professional development [TPD] for online and blended learning [OBL]: a systematic meta-aggregative review", we apply their proposed framework of important components of TPD for OBL to the support we provided to primary and secondary teachers as they engaged with online education during the COVID-19 pandemic. We reflect on observations of particular challenges for school teachers and the reasons behind them. While this framework is a useful reflection tool to guide professional learning for teachers beyond the emergency situations, we found that it is biased towards TPD for OBL in higher education settings. Thus, we suggest future work to differentiate educational levels in order to account for operational differences.}, } @article {pmid33049349, year = {2020}, author = {Beni, MD}, title = {An integrative explanation of action.}, journal = {Bio Systems}, volume = {198}, number = {}, pages = {104266}, doi = {10.1016/j.biosystems.2020.104266}, pmid = {33049349}, issn = {1872-8324}, mesh = {Adaptation, Psychological/physiology ; Animals ; Brain/*physiology ; Cognition/*physiology ; Humans ; Intelligence/*physiology ; Motivation/*physiology ; Perception/*physiology ; Self Concept ; Social Behavior ; }, abstract = {The Predictive Processing Theory (PP) and its foundational Free Energy Principle (FEP) provide a unifying theoretical groundwork that subsumes theories of perception, cognition, and action. Recently Colin Klein (2018) contends that PP-FEP cannot explain adaptive action with the same force that they deal with perceptions. In his answer to the objection, Clark (2020) points out that FEP explains action, desire and motivation on the basis of minimisation of energy. I argue that this answer begs the question of the unifying framework of FEP. I assume that FEP-PP alone cannot provide an ultimately compelling explanation of action. However, I argue that when paired with a high level theory of psychology, such as Theriault et al.'s (2020) theory of social conformation in terms of the sense of should, the coupled theories provide an inclusive, symmetrical explanation of action. The symmetry of explanations is not a gap but a feature, on this specific occasion.}, } @article {pmid33044220, year = {2020}, author = {Longtin, C and Tousignant-Laflamme, Y and Coutu, MF}, title = {A logic model for a self-management program designed to help workers with persistent and disabling low back pain stay at work.}, journal = {Work (Reading, Mass.)}, volume = {67}, number = {2}, pages = {395-406}, doi = {10.3233/WOR-203289}, pmid = {33044220}, issn = {1875-9270}, mesh = {Focus Groups ; Humans ; Logic ; *Low Back Pain/therapy ; *Self-Management ; Surveys and Questionnaires ; }, abstract = {BACKGROUND: Workers with persistent disabling low back pain (LBP) often encounter difficulty staying at work. Self-management (SM) programs can offer interesting avenues to help workers stay at work.

OBJECTIVE: To establish the plausibility of a logic model operationalizing a SM program designed to help workers with persistent disabling LBP stay at work.

METHODS: We used a qualitative design. A preliminary version of the logic model was developed based on the literature and McLaughlin et al.'s framework for logic models. Clinicians in work rehabilitation completed an online survey on the plausibility of the logic model and proposed modifications, which were discussed in a focus group. Thematic analyses were performed.

RESULTS: Participants (n = 11) found the model plausible, contingent upon a few modifications. They raised the importance of making more explicit the margin of maneuver or "job leeway" for a worker who is trying to stay at work and suggested emphasizing a capability approach. Enhancing the workers' perceived self-efficacy and communication skills were deemed essential tasks of the model.

CONCLUSION: A plausible logic model for a SM program designed for workers with disabling LBP stay at work was developed. The next step will be to assess its acceptability with potential users.}, } @article {pmid33034272, year = {2022}, author = {Taçgın, E and Sağır, Z}, title = {Development of an intelligent knowledge base for identification of accident causes based on Fu et al.'s model.}, journal = {International journal of occupational safety and ergonomics : JOSE}, volume = {28}, number = {2}, pages = {824-841}, doi = {10.1080/10803548.2020.1831786}, pmid = {33034272}, issn = {2376-9130}, mesh = {*Accidents, Occupational/prevention & control ; Humans ; *Knowledge Bases ; }, abstract = {In this study, an intelligent knowledge base (IKB) is developed based on a model developed by Fu et al. for identification of accident causes, which may play a significant role in preventing accidents. This IKB has been generated using eight sample accidents reported in the literature and tested by two additional accidents. The causes of these sample accidents were identified according to a model taxonomy developed by Fu et al. For the test, an oil spill and a refinery accident are considered in two case studies. This study proved 89.47 and 73.01% success rates, respectively, for the identification of additional accidents causes based on the developed IKB. These results obtained from only eight sample accidents are considered promising because as the number of sample accidents increases, the success rates are expected to increase further. This IKB was prepared as part of a more comprehensive intelligent system to be developed.}, } @article {pmid33030935, year = {2021}, author = {Genschow, O and Westfal, M and Crusius, J and Bartosch, L and Feikes, KI and Pallasch, N and Wozniak, M}, title = {Does social psychology persist over half a century? A direct replication of Cialdini et al.'s (1975) classic door-in-the-face technique.}, journal = {Journal of personality and social psychology}, volume = {120}, number = {2}, pages = {e1-e7}, doi = {10.1037/pspa0000261}, pmid = {33030935}, issn = {1939-1315}, mesh = {Adolescent ; Adult ; Emotions ; Female ; History, 20th Century ; Humans ; Male ; *Persuasive Communication ; Probability ; Psychology, Social/*history ; Social Behavior ; Surveys and Questionnaires ; Young Adult ; }, abstract = {Many failed replications in social psychology have cast doubt on the validity of the field. Most of these replication attempts have focused on findings published from the 1990s on, ignoring a large body of older literature. As some scholars suggest that social psychological findings and theories are limited to a particular time, place, and population, we sought to test whether a classical social psychological finding that was published nearly half a century ago can be successfully replicated in another country on another continent. To this end, we directly replicated Cialdini et al.'s (1975) door-in-the-face (DITF) technique according to which people's likelihood to comply with a target request increases after having turned down a larger request. Thereby, we put the reciprocal concessions theory-the original process explanation of the DITF technique-to a critical test. Overall, compliance rates in our replication were similarly high as those Cialdini et al. (1975) found 45 years ago. That is, participants were more likely to comply with a target request after turning down an extreme request than participants who were exposed to the target request only or to a similarly small request before being exposed to the target request. These findings support the idea that reciprocity norms play a crucial role in DITF strategies. Moreover, the results suggest that at least some social psychological findings can transcend a particular time, place, and population. Further theoretical implications are discussed. (PsycInfo Database Record (c) 2021 APA, all rights reserved).}, } @article {pmid33028483, year = {2020}, author = {Kaplan, MS and Kerr, WC and McFarland, BH and Bensley, K and Caetano, R and Giesbrecht, N and Monnat, SM and Nolte, KB}, title = {A Reply to Monteiro et al.'s (2020) 'Alcohol Policy and Coronavirus: An Open Research Agenda'.}, journal = {Journal of studies on alcohol and drugs}, volume = {81}, number = {5}, pages = {687-688}, pmid = {33028483}, issn = {1938-4114}, support = {P50 AA005595/AA/NIAAA NIH HHS/United States ; }, } @article {pmid33027061, year = {2020}, author = {Elhai, JD and Yang, H and Levine, JC}, title = {Applying fairness in labeling various types of internet use disorders. •.}, journal = {Journal of behavioral addictions}, volume = {9}, number = {4}, pages = {924-927}, pmid = {33027061}, issn = {2063-5303}, mesh = {*Behavior, Addictive/diagnosis ; Humans ; International Classification of Diseases ; Internet ; Internet Use ; Smartphone ; *Video Games ; }, abstract = {We comment on arguments about internet and smartphone use disorders by Montag, Wegmann, Sariyska, Demetrovics, and Brand (2020). Although not currently official diagnoses, we emphasize that for some individuals, excessive internet/smartphone use can have dangerous consequences. We discuss the challenges with ICD-11 codifying only internet gaming as an internet use-related disorder, neglecting other types of excessive internet users. Montag et al.'s approach to classifying a broader range of internet use disorders seems more fair than the current system in aiding individuals needing treatment resources for excessive internet use.}, } @article {pmid33025905, year = {2020}, author = {Mevel, R and Steiner, I and Mason, S and Galbraith, LC and Patel, R and Fadlullah, MZ and Ahmad, I and Leung, HY and Oliveira, P and Blyth, K and Baena, E and Lacaud, G}, title = {RUNX1 marks a luminal castration-resistant lineage established at the onset of prostate development.}, journal = {eLife}, volume = {9}, number = {}, pages = {}, pmid = {33025905}, issn = {2050-084X}, support = {19565/CRUK_/Cancer Research UK/United Kingdom ; C596/A17196/CRUK_/Cancer Research UK/United Kingdom ; 29799/CRUK_/Cancer Research UK/United Kingdom ; 22904/CRUK_/Cancer Research UK/United Kingdom ; 19996/CRUK_/Cancer Research UK/United Kingdom ; C5759/A20971/CRUK_/Cancer Research UK/United Kingdom ; }, mesh = {Animals ; Cell Lineage ; Core Binding Factor Alpha 2 Subunit/metabolism/*physiology ; Epithelium/metabolism ; Male ; Mice ; Orchiectomy ; Prostate/cytology/*growth & development/metabolism ; }, abstract = {The characterization of prostate epithelial hierarchy and lineage heterogeneity is critical to understand its regenerative properties and malignancies. Here, we report that the transcription factor RUNX1 marks a specific subpopulation of proximal luminal cells (PLCs), enriched in the periurethral region of the developing and adult mouse prostate, and distinct from the previously identified NKX3.1[+] luminal castration-resistant cells. Using scRNA-seq profiling and genetic lineage tracing, we show that RUNX1[+] PLCs are unaffected by androgen deprivation, and do not contribute to the regeneration of the distal luminal compartments. Furthermore, we demonstrate that a transcriptionally similar RUNX1[+] population emerges at the onset of embryonic prostate specification to populate the proximal region of the ducts. Collectively, our results reveal that RUNX1[+] PLCs is an intrinsic castration-resistant and self-sustained lineage that emerges early during prostate development and provide new insights into the lineage relationships of the prostate epithelium.}, } @article {pmid33023660, year = {2020}, author = {Millenson, ML}, title = {"Will you hear my voice?": to engage older patients online, listen to them about their lives offline.}, journal = {Israel journal of health policy research}, volume = {9}, number = {1}, pages = {51}, pmid = {33023660}, issn = {2045-4015}, mesh = {Aged ; Betacoronavirus ; COVID-19 ; *Coronavirus Infections ; *Health Planning ; Humans ; Israel ; *Pandemics ; *Pneumonia, Viral ; SARS-CoV-2 ; }, abstract = {The scope of health information and health care services available online is rapidly expanding. At the same time, COVID-19 is causing vulnerable elders to reconsider in-person provider visits. In that context, recently published research by Y. Mizrachi et al. examining obstacles to the use of online health services (OHS) among adults age 50 and up takes on new importance. An iconic Israeli song begins, "Will you hear my voice?" (Hebrew Songs. Zemer Nugeh (Hatishmah Koli), 2020). What makes Mizrachi et al.'s findings particularly intriguing, despite several caveats, is the manner in which they demonstrated a commitment to genuinely listen to individual voices. The researchers spoke "openly and bluntly" with interviewees as peers and were rewarded with "specific, well-defined and applicable answers with the potential to be used." The most striking findings came in candid answers that went beyond the factors intrinsic to the online offerings and addressed important factors in what regular Internet users often refer to as IRL ("in real life"), such as support from family. The necessity of avoiding preconceptions about the most effective manner to engage patients underscores the importance of patient and family advisory councils (PFACs). PFACs, increasingly being adopted by health care organizations globally, provide an ongoing ability to listen and respond to the "patient voice." Effectively addressing obstacles to older adults' use of the full range of online health resources will require the involvement not just of health plans and government, but also of voluntary organizations, providers, families and others integral to users' offline "real lives." Sustained, focused listening must be a central part of that effort.}, } @article {pmid33018293, year = {2020}, author = {Wang, Y and Yang, T and Huang, W}, title = {Limited-Angle Computed Tomography Reconstruction using Combined FDK-Based Neural Network and U-Net.}, journal = {Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference}, volume = {2020}, number = {}, pages = {1572-1575}, doi = {10.1109/EMBC44109.2020.9176040}, pmid = {33018293}, issn = {2694-0604}, mesh = {Algorithms ; Artifacts ; *Neural Networks, Computer ; Signal-To-Noise Ratio ; *Tomography, X-Ray Computed ; }, abstract = {The limited-angle cone-beam Computed Tomography (CT) is often used in C-arm for clinical diagnosis with the advantages of cheap cost and radiation dose reduction. However, due to incomplete projection data, the 3-dimensional CT images reconstructed by conventional methods, such as the Feldkamp, Davis and Kres (FDK) algorithm [1], suffer from heavy artifacts and missing features. In this paper, we propose a novel pipeline of neural networks jointly by a FDK-based neural network revisited from Würfl et al.'s work [2] and an image domain U-Net to enhance the 3-dimensional reconstruction quality for limited projection sinogram less than 180 degrees, i.e. 145 degrees in our work. Experimental results, on simulated projections of real-scan CTs, show that the proposed pipeline can reduce some of the major artifacts caused by the limited views while keep the key features, with a 16.60% improvement than Würfl et al.'s work on peak signal-to-noise ratio.}, } @article {pmid33017261, year = {2020}, author = {Caron, EE and Reynolds, MG and Ralph, BCW and Carriere, JSA and Besner, D and Smilek, D}, title = {Does Posture Influence the Stroop Effect?.}, journal = {Psychological science}, volume = {31}, number = {11}, pages = {1452-1460}, doi = {10.1177/0956797620953842}, pmid = {33017261}, issn = {1467-9280}, mesh = {*Color Perception ; Humans ; *Posture ; Reaction Time ; Stroop Test ; }, abstract = {Rosenbaum, Mama, and Algom (2017) reported that participants who completed the Stroop task (i.e., name the hue of a color word when the hue and word meaning are congruent or incongruent) showed a smaller Stroop effect (i.e., the difference in response times between congruent and incongruent trials) when they performed the task standing than when sitting. We report five attempted replications (analyzed sample sizes: N = 108, N = 108, N = 98, N = 78, and N = 51, respectively) of Rosenbaum et al.'s findings, which were conducted in two institutions. All experiments yielded the standard Stroop effect, but we failed to detect any consistent effect of posture (sitting vs. standing) on the magnitude of the Stroop effect. Taken together, the results suggest that posture does not influence the magnitude of the Stroop effect to the extent that was previously suggested.}, } @article {pmid33017164, year = {2020}, author = {Brewin, CR and Li, H and McNeilis, J and Ntarantana, V and Unsworth, C}, title = {On repression, and avoiding red herrings.}, journal = {Journal of experimental psychology. General}, volume = {149}, number = {10}, pages = {2001-2004}, doi = {10.1037/xge0000973}, pmid = {33017164}, issn = {1939-2222}, mesh = {Emotions ; Humans ; *Memory ; *Repression, Psychology ; Surveys and Questionnaires ; }, abstract = {In this response to Otgaar et al. (2020), we point out that their concern with the notion of unconscious repression is a classic example of a red herring, as it has never been endorsed as an explanation of recovered memories. We also note that Otgaar et al. have misunderstood the purpose of our article (Brewin, Li, Ntarantana, Unsworth, & McNeilis, 2019). Its aim was to demonstrate that many of the claims made by psychologists about the public's views on memory do not rest on sound methodology. Beliefs about repression featured as one example, but it was not our objective to establish what the public do think about repression. We welcome Otgaar et al.'s additional data but regret that they have repeated the basic error we highlighted, the reliance on a single questionnaire item to assess beliefs about highly complex topics. Nevertheless, their and our findings clearly indicate that understanding of the public's views on repression remains extremely limited, and insufficient to meaningfully contribute to legal processes. (PsycInfo Database Record (c) 2020 APA, all rights reserved).}, } @article {pmid33011713, year = {2020}, author = {Griffiths, MD}, title = {Internet use disorders: What's new and what's not?. •.}, journal = {Journal of behavioral addictions}, volume = {9}, number = {4}, pages = {934-937}, pmid = {33011713}, issn = {2063-5303}, mesh = {*Behavior, Addictive ; Humans ; Internet ; Internet Addiction Disorder ; *Internet Use ; Smartphone ; }, abstract = {This commentary critiques the recent paper by Montag et al. (2019) and (i) argues that there are a number of issues that are presented as contemporary but have been discussed in the internet addiction literature for over 20 years, (ii) argues that generalized internet use disorder (IUD)/smartphone use disorder (SmUD) and specific IUD/SmUD may mean different things to different scholars, (iii) suggests that online activities that involve content creation often utilize nonmobile devices, and (iv) suggests that there are some potentially problematic online behaviors that are not included as major activities in the proposed in Montag et al.'s taxonomy of internet-related problematic behaviors.}, } @article {pmid33002029, year = {2020}, author = {Chakraborty, A and Ikeda, Y}, title = {Testing "efficient supply chain propositions" using topological characterization of the global supply chain network.}, journal = {PloS one}, volume = {15}, number = {10}, pages = {e0239669}, pmid = {33002029}, issn = {1932-6203}, abstract = {In this paper, we study the topological properties of the global supply chain network in terms of its degree distribution, clustering coefficient, degree-degree correlation, bow-tie structure, and community structure to test the efficient supply chain propositions proposed by E. J.S. Hearnshaw et al. The global supply chain data in the year 2017 are constructed by collecting various company data from the web site of Standard & Poor's Capital IQ platform. The in- and out-degree distributions are characterized by a power law of the form of γin = 2.42 and γout = 2.11. The clustering coefficient decays [Formula: see text] with an exponent βk = 0.46. The nodal degree-degree correlations 〈knn(k)〉 indicates the absence of assortativity. The bow-tie structure of giant weakly connected component (GWCC) reveals that the OUT component is the largest and consists 41.1% of all firms. The giant strong connected component (GSCC) is comprised of 16.4% of all firms. We observe that upstream or downstream firms are located a few steps away from the GSCC. Furthermore, we uncover the community structures of the network and characterize them according to their location and industry classification. We observe that the largest community consists of the consumer discretionary sector based mainly in the United States (US). These firms belong to the OUT component in the bow-tie structure of the global supply chain network. Finally, we confirm the validity of Hearnshaw et al.'s efficient supply chain propositions, namely Proposition S1 (short path length), Proposition S2 (power-law degree distribution), Proposition S3 (high clustering coefficient), Proposition S4 ("fit-gets-richer" growth mechanism), Proposition S5 (truncation of power-law degree distribution), and Proposition S7 (community structure with overlapping boundaries) regarding the global supply chain network. While the original propositions S1 just mentioned a short path length, we found the short path from the GSCC to IN and OUT by analyzing the bow-tie structure. Therefore, the short path length in the bow-tie structure is a conceptual addition to the original propositions of Hearnshaw.}, } @article {pmid33001701, year = {2021}, author = {Kuhlmann, BG and Brubaker, MS and Pfeiffer, T and Naveh-Benjamin, M}, title = {Longer resistance of associative versus item memory to interference-based forgetting, even in older adults.}, journal = {Journal of experimental psychology. Learning, memory, and cognition}, volume = {47}, number = {3}, pages = {422-438}, doi = {10.1037/xlm0000963}, pmid = {33001701}, issn = {1939-1285}, support = {//Deutsche Forschungsgemeinschaft/ ; //University of Missouri Research Council/ ; }, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Aging/*psychology ; *Association Learning ; Humans ; *Memory ; Memory Disorders/*psychology ; *Recognition, Psychology ; Young Adult ; }, abstract = {Few studies have compared interference-based forgetting between item versus associative memory. The memory-system dependent forgetting hypothesis (Hardt, Nader, & Nadel, 2013) predicts that effects of interference on associative memory should be minimal because its hippocampal representation allows pattern separation even of highly similar information. In contrast, there should be strong interference effects on extra-hippocampally represented item memory. We tested this prediction in behavioral data from 3 experiments using continuous recognition paradigms. Given older adults' greater deficits in associative than item memory, we also compared younger and older adults to test whether this associative deficit extends to greater interference susceptibility in older adults' associative memory. Experiment 1 examined item-item associative memory with participants studying unrelated word pairs continuously intermixed with item (single words) and associative (intact vs. recombined pairs) recognition tests across interference-filled lags. Experiments 2 and 3 examined item-context (i.e., source) associative memory with participants studying words in different spatial positions continuously intermixed with source-monitoring tests (presented on top vs. on bottom vs. new?) across interference-filled lags (Experiment 3 controlling for delay/decay-based effects). In all experiments, item memory declined from the first lag on. In contrast, associative memory initially remained stable, with strong evidence for null effects of interference even in older adults, but showed some declines at later lags. The data supports Hardt et al.'s proposal of differential interference-based forgetting in item versus associative memory. The results further show that the age-related associative memory deficit does not extend to greater interference-based forgetting in older adults' associative memory. (PsycInfo Database Record (c) 2021 APA, all rights reserved).}, } @article {pmid33001671, year = {2021}, author = {Patrick, CJ and Joyner, KJ and Watts, AL and Lilienfeld, SO and Somma, A and Fossati, A and Donnellan, MB and Hopwood, CJ and Sellbom, M and Drislane, LE and Edens, JF and Verona, E and Latzman, RD and Sica, C and Benning, SD and Morey, LC and Hicks, BM and Fanti, KA and Blonigen, DM and Molto, J and Kramer, MD and Krueger, RF}, title = {Latent variable modeling of item-based factor scales: Comment on Triarchic or septarchic?-Uncovering the Triarchic Psychopathy Measure's (TriPM) Structure, by Roy et al.}, journal = {Personality disorders}, volume = {12}, number = {1}, pages = {16-23}, doi = {10.1037/per0000424}, pmid = {33001671}, issn = {1949-2723}, support = {U54 MH091657/MH/NIMH NIH HHS/United States ; }, mesh = {*Antisocial Personality Disorder/diagnosis ; Humans ; Latent Class Analysis ; *Parents ; Psychotherapy ; Research Design ; }, abstract = {We critique Roy et al.'s (2020; this issue) approach to characterizing the item-level factor structure of the three scales of the Triarchic Psychopathy Measure (TriPM), in light of the manner in which the TriPM scales were developed, the purposes they were designed to serve, and the growing body of evidence supporting their construct validity. We focus on three major points: (1) The TriPM scales are item-based factor scales - i.e., item sets designed to index broad factors of larger multi-scale (parent) inventories; (2) item-level structural analysis can be useful for representing broad dimensions tapped by such scales, but it cannot be expected to provide an accurate picture of narrower subdimensions (facets) assessed by their parent inventories; and (3) it is critical to consider the nomological networks of the TriPM scales (and other triarchic scale measures) in appraising their effectiveness as operationalizations of the triarchic model constructs. We illustrate the first and second of these points by applying Roy et al.'s analytic approach to the trait scales of the NEO-FFI, which were developed to index broad personality dimensions of the multi-scale NEO-PI-R. We address the third point with reference to the growing body of literature supporting the construct validity of the TriPM scales and demonstrating their utility for advancing an integrative understanding of psychopathy. (PsycInfo Database Record (c) 2021 APA, all rights reserved).}, } @article {pmid32999725, year = {2020}, author = {Gueret, G and Lefebvre, P and Le Maguet, P and Fabre, R}, title = {Acute kidney injury after aneurysmal subarachnoid hemorrhage: is chloride really responsible?.}, journal = {Journal of intensive care}, volume = {8}, number = {}, pages = {73}, pmid = {32999725}, issn = {2052-0492}, abstract = {Sadan et al. find an association between acute kidney injury and high chloride containing a hypertonic solution. Recent large prospective non-randomized studies bring conflicting results on the relationship between chloride and acute kidney injury. We discuss Sadan et al.'s results according to the recent literature.}, } @article {pmid32993367, year = {2021}, author = {Hallaran, AJ and Edge, DS and Almost, J and Tregunno, D}, title = {New Registered Nurse Transition to the Workforce and Intention to Leave: Testing a Theoretical Model.}, journal = {The Canadian journal of nursing research = Revue canadienne de recherche en sciences infirmieres}, volume = {53}, number = {4}, pages = {384-396}, doi = {10.1177/0844562120957845}, pmid = {32993367}, issn = {1705-7051}, mesh = {Cross-Sectional Studies ; Humans ; *Intention ; Job Satisfaction ; Models, Theoretical ; *Nurses ; Personnel Turnover ; Surveys and Questionnaires ; Workforce ; }, abstract = {BACKGROUND: The transition of new nurses into practice has been identified as challenging, and new nurses report having intentions to leave (ITL) jobs. Concerns of ITL are worrisome for the nursing profession, especially when faced with the need to replace an aging nursing workforce and to maintain quality patient care.

PURPOSE: Guided by components of Meleis et al.'s mid-range transition theory, the purpose of this study was to test a theoretical model linking transition and ITL, as well as the personal, community and societal conditions of transition.

METHODS: A predictive, non-experimental design using cross-sectional data was employed. Ontario registered nurses, who had graduated within two years, were randomly selected to complete a mailed questionnaire in 2015 (N = 217). Structural equation modeling was undertaken to test the model.

RESULTS: The new nurses reported a relatively positive transition; yet, 44% of the respondents indicated leaving their first job, and 1% departed the nursing profession. A revised model of the constructs showed a more adequate fit with the data, but overall, the hypothesized model was not supported and methodological validity of tools questioned. From the modeling, lower role stress led to a positive transition.

CONCLUSIONS: Given organizational and governmental investments in orientation and transition programs, challenges in measuring transition and ITL requires additional research. Our findings highlight the value of organizations supporting new nurses by reducing role stress through reasonable workloads and expectations, which in turn contributes to a positive transition.}, } @article {pmid32986809, year = {2020}, author = {Karim, HMR and Bhakta, P and Esquinas, AM}, title = {An enquiry to Choi et al.'s surgical outcome and prognosis of lung cancer in patients with chronic lung disease.}, journal = {European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery}, volume = {}, number = {}, pages = {}, doi = {10.1093/ejcts/ezaa298}, pmid = {32986809}, issn = {1873-734X}, } @article {pmid32986385, year = {2020}, author = {Rahimi Moghadam, S and Khanjani, N and Mohamadyan, M and Emkani, M and Yari, S and Layegh Tizabi, MN and Ganjali, A}, title = {Changes in Spirometry Indices and Lung Cancer Mortality Risk Estimation in Concrete Workers Exposed io Crystalline Silica.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {21}, number = {9}, pages = {2811-2817}, pmid = {32986385}, issn = {2476-762X}, mesh = {Adult ; Air Pollutants, Occupational/*adverse effects ; Construction Materials/*adverse effects ; Cross-Sectional Studies ; Follow-Up Studies ; Humans ; Inhalation Exposure/adverse effects ; Iran ; Lung Neoplasms/epidemiology/etiology/*mortality/pathology ; Male ; Occupational Diseases/epidemiology/etiology/*mortality/pathology ; Occupational Exposure/adverse effects ; Prognosis ; Risk Assessment/*methods ; Silicon Dioxide/*adverse effects ; Spirometry/*methods ; Survival Rate ; }, abstract = {The health of workers in the concrete and cement industries can be at risk due to occupational exposure to silica dust. The purpose of this study was to evaluate the changes of pulmonary parameters and risk of mortality from lung cancer in concrete workers exposed to crystalline silica. This cross-sectional study was performed on 72 male workers exposed to silica at a concrete manufacturing plant in Neyshabur, Iran. Respiratory zone air sampling was performed using the standard NIOSH7602 method using individual sampling pumps and membrane filters. Then, the amount of silica in the samples was determined using the Fourier Transform Infrared technique. The risk of death from lung cancer was determined using Rice et al.'s model. Respiratory indices were measured using a spirometer. Data were analyzed by the SPSS 20 software. Occupational exposure to silica was 0.025 mg/m3 and mortality was estimated to be 7-94 per thousand. All spirometry indices significantly decreased during these 4 years of exposure to silica dust. The respiratory pattern of 22% of the exposed workers was obstructive and this prevalence was significantly higher than the control group. The results showed that although the average occupational exposure to silica in these concrete workers was below the recommended threshold of national and international organizations, their risk of death was significantly higher; and workers' lung indices had significantly decreased over four years. Therefore, appropriate measures should be taken to reduce silica exposure among these workers.}, } @article {pmid32964183, year = {2020}, author = {Pfeuffer, CU}, title = {Item-Specificity and Intention in Episodic Memory.}, journal = {Journal of cognition}, volume = {3}, number = {1}, pages = {24}, pmid = {32964183}, issn = {2514-4820}, abstract = {Schmidt et al.'s (2020) PEP model accurately reflects the complexity of task switching based on bottom-up assumptions and episodic memory, re-evaluating the contribution of commonly presumed top-down processes. Extending it to long-term bindings and their item-specific effects could eludicate puzzling findings regarding the independence of long-term bindings between stimuli, responses, and task-specific categorizations as well as the relation between short-term and long-term bindings. Moreover, ideomotor theories of action control provide a bottom-up basis of incorporating volition and intentional action into the PEP model which is currently restricted to stimulus-based action.}, } @article {pmid32956743, year = {2020}, author = {Rice, PA and Aungst, J and Cooper, J and Bandele, O and Kabadi, SV}, title = {Letter to the editor responding to Anderson et al.'s 2020 letter regarding Rice et al. (2020).}, journal = {Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association}, volume = {145}, number = {}, pages = {111755}, doi = {10.1016/j.fct.2020.111755}, pmid = {32956743}, issn = {1873-6351}, } @article {pmid32948946, year = {2021}, author = {Lasisi, TT and Eluwole, KK}, title = {Is the weather-induced COVID-19 spread hypothesis a myth or reality? Evidence from the Russian Federation.}, journal = {Environmental science and pollution research international}, volume = {28}, number = {4}, pages = {4840-4844}, pmid = {32948946}, issn = {1614-7499}, mesh = {*COVID-19 ; Humans ; Pandemics ; Russia ; SARS-CoV-2 ; Weather ; }, abstract = {Several conspiracy theories and hypotheses have been postulated by some individuals from various strata of governance globally concerning the outbreak and spread of the novel coronavirus in the last quarter of 2019. A pertinent hypothesis is the correlation of meteorological elements to the spread of the pandemic. To verify this claim and also confirm the initial findings of Tosepu et al.'s (2020), this study investigated the Spearman rank-order correlation of the number of confirmed COVID-19 cases in the Russian Federation with temperature-maximum, minimum, and average as well as precipitation. Our findings indicated a stronger correlation between average temperature (rs = 0.75[***]) and also recorded significant correlations for the other variants of temperature. Hence, the hypothesis of weather-induced COVID-19 spread is substantiated.}, } @article {pmid32946300, year = {2022}, author = {Pei, M and Zhao, C and Gao, F and Qu, Y and Liang, A and Xiao, J and Zhang, M}, title = {Authors Reply to Letter to the Editor - In Response To: Comment on Pei M et al.'s "Analysis of Parafoveal Microvascular Abnormalities in Behcet's Uveitis Using Projection-resolved Optical Coherence Tomographic Angiography".}, journal = {Ocular immunology and inflammation}, volume = {30}, number = {2}, pages = {522-523}, doi = {10.1080/09273948.2020.1807201}, pmid = {32946300}, issn = {1744-5078}, mesh = {Angiography ; *Behcet Syndrome/complications/diagnosis ; Fluorescein Angiography ; Humans ; Tomography, Optical Coherence/methods ; *Uveitis/diagnosis/etiology ; }, } @article {pmid32930452, year = {2021}, author = {Malik, O}, title = {Commentary: What is unsought will go undetected - a commentary on Rodin et al. (2020).}, journal = {Child and adolescent mental health}, volume = {26}, number = {1}, pages = {54-55}, doi = {10.1111/camh.12401}, pmid = {32930452}, issn = {1475-357X}, mesh = {Humans ; Knowledge ; *Tic Disorders ; *Tics ; *Tourette Syndrome ; Uganda/epidemiology ; }, abstract = {Rodin et al.'s study (2020) on the belief, knowledge and attitudes about tics amongst health professionals in Uganda is a preliminary yet an important step towards challenging the current thinking amongst clinicians and academics working with tics, which is that tics are hardly seen in or are absent in the sub-Saharan African population and it has been psotulated that this phenomenon is considered to be explained by genetics.}, } @article {pmid32928446, year = {2020}, author = {McNamara, C}, title = {Comment on Azad et al.'s "Cost-utility of colorectal cancer screening at age 40 years old for average-risk patients".}, journal = {Preventive medicine}, volume = {139}, number = {}, pages = {106140}, doi = {10.1016/j.ypmed.2020.106140}, pmid = {32928446}, issn = {1096-0260}, mesh = {Adult ; *Colorectal Neoplasms ; *Early Detection of Cancer ; Humans ; Occult Blood ; }, } @article {pmid32927241, year = {2020}, author = {Wiegert, EVM and de Oliveira, LC and Calixto-Lima, L and Mota E Silva Lopes, MSD and Peres, WAF}, title = {Cancer cachexia: Comparing diagnostic criteria in patients with incurable cancer.}, journal = {Nutrition (Burbank, Los Angeles County, Calif.)}, volume = {79-80}, number = {}, pages = {110945}, doi = {10.1016/j.nut.2020.110945}, pmid = {32927241}, issn = {1873-1244}, mesh = {Brazil ; *Cachexia/diagnosis/epidemiology/etiology ; Humans ; *Neoplasms/complications/diagnosis ; Prognosis ; Prospective Studies ; }, abstract = {OBJECTIVES: Cancer cachexia (CC) is a multifactorial syndrome that is associated with worse outcomes. Several criteria for its diagnosis have been suggested, but notable disparities exist. This study compared different diagnostic criteria for CC in patients with incurable cancer who are in palliative care.

METHODS: A prospective cohort study was conducted at the National Cancer Institute in Brazil. Patients were classified by three CC diagnostic criteria, and comparisons between clinical, nutritional, and functional variables were verified according to the CC stage identified. Kaplan-Meier survival curves and Cox regression were used for the survival analysis. Concordance statistics were used to test the prognostic predictive accuracy of the criteria.

RESULTS: The prevalence of cachexia in the 1384 patients included in the study varied from 13.8% to 53.9% according to the classification criteria used. All criteria distinguished noncachectic patients from other categories according to the majority of the domains studied. However, the results were inconsistent in distinguishing patients with intermediate cachexia (mainly precachexia) from noncachectic and cachectic patients. Patients with cachexia or refractory cachexia faced a higher risk of 90-d mortality. The criteria described by Vigano et al. were found to be better at distinguishing the stages of CC regarding overall survival (hazard ratio increases according to CC severity: 1.87 to 2.87; concordance statistic: 0.74).

CONCLUSIONS: Our results demonstrate the disparities in existing CC diagnostic criteria and their inability to discriminate intermediate stages. Vigano et al.'s criteria is/was the most effective in predicting the prognosis. The development of new diagnostic criteria to improve CC classification requires future exploration.}, } @article {pmid32923998, year = {2020}, author = {Wilson, A and Neilsen, P and Berry, R and Seckiner, D and Mallett, X}, title = {Quantifying human post-mortem movement resultant from decomposition processes.}, journal = {Forensic science international. Synergy}, volume = {2}, number = {}, pages = {248-261}, pmid = {32923998}, issn = {2589-871X}, abstract = {BACKGROUND: Post-mortem movement is highly significant in unexplained death investigations, as body position or the position of remains helps to determine cause and manner of death, as well as potentially the circumstances surrounding death. Therefore, understanding post-mortem movement is of forensic relevance in death scene assessments.

PURPOSE: The aim of this study was to quantify post-mortem movement in anatomical structures of a human donor during decomposition in an Australian environment, an evaluation that has not previously been undertaken.

METHODS: The aim was achieved using time-lapse images of a human donor decomposing in order to capture the post-mortem movement over a 16-month period. Megyesi et al.'s [1] total body score system was used to quantify the decomposition of the donor in each image to determine the decomposition stage. ImageJ software was used to determine the distance from static landmarks to anatomical structures of interest in each image to allow for quantification.

RESULTS: Early decomposition progressed rapidly, and advanced decomposition plateaued at 41 post-mortem interval days with a total body score of 24. The results support the conclusion that post-mortem movement does occur in all limbs of the donor. The anatomical structure that produced the most movement was the right styloid process of the radius, moving a total distance of 51.65 cm. A surprising finding of the study was that most post-mortem movement occurs in the advanced decomposition stage, with the lower limbs being the most active.

CONCLUSION: This study supports that post-mortem movement can be quantified using time-lapse imagery, with results supporting movement in all limbs, a process that was active for the entire study period. An interesting finding was that the decomposition plateaued in the advanced stage with the donor remaining in mummification, and not reaching skeletonization after 16 months in situ. These findings are of significant importance to police in death scene assessments and forensic investigations.}, } @article {pmid32909912, year = {2021}, author = {Abbasi, P and Yoosefi-Lebni, J and Jalali, A and Ziapour, A and Nouri, P}, title = {Causes of the plagiarism: A grounded theory study.}, journal = {Nursing ethics}, volume = {28}, number = {2}, pages = {282-296}, doi = {10.1177/0969733020945753}, pmid = {32909912}, issn = {1477-0989}, mesh = {Grounded Theory ; Humans ; Iran ; *Plagiarism ; Students ; *Universities ; }, abstract = {BACKGROUND: Plagiarism is an ethical and academic issue, which is affected by several factors.

OBJECTIVES: This study is an attempt to introduce a model for elaborating on the causes of plagiarism in Iran.

RESEARCH DESIGN: The study was carried out as a grounded theory study.

Data were collected through in-depth semi-structured interviews with 32 university professors and postgraduate students at Iranian universities of medical sciences. The participants were selected through purposeful and theoretical sampling. Data analysis was done following Strauss et al.'s work. To ensure study rigor, Lincoln and Guba's measures were used.

ETHICAL CONSIDERATIONS: All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

RESULTS: A conceptual model of the causes of plagiarism was developed based on analyzing and coding the data. The main core of the model was the emergence of plagiarism, and other cores were (1) causal condition: lack of skills, pressure by education system, and lack of awareness; (2) intervening factors: technological advances, legal gaps, and lack of efficient supervision; (3) ground factors: personal traits and attitudes of the academic community; (4) strategy and interventions: role model, supervision, national/international coordination, and higher awareness; (5) outcomes: regeneration of plagiarism and negative attitudes toward Iranian authors in the world academic communities.

CONCLUSION: Several factors affect plagiarism. Among the approaches to attenuate plagiarism in Iranian academic communities are improving self-esteem and self-efficacy in Iranian researchers, emphasizing on quality rather than quantity of published works, discouraging boasting attitudes in the practitioners, denouncing intense competition among researchers, and introducing clear laws and severe punishments for plagiarism.}, } @article {pmid32899217, year = {2020}, author = {Umegaki, H and Suzuki, Y and Yamada, Y and Komiya, H and Watanabe, K and Nagae, M and Kuzuya, M}, title = {Association of the Qualitative Clock Drawing Test with Progression to Dementia in Non-Demented Older Adults.}, journal = {Journal of clinical medicine}, volume = {9}, number = {9}, pages = {}, pmid = {32899217}, issn = {2077-0383}, abstract = {To evaluate the predictability of progression of cognitive impairment to dementia using qualitative clock drawing test (CDT) scores, we administered both the CDT using Cahn et al.'s qualitative scoring system and the Mini-Mental State Examination (MMSE) to assess cognitive function in non-demented older individuals attending a memory clinic at a university hospital. Patients visiting the clinic for assessment of cognitive function between January 2015 and December 2019 were enrolled, and only those who were diagnosed as not having dementia at the time of initial assessment completed a follow-up assessment at 1 y (n = 163). To examine any association of qualitative CDT score with progression to dementia, multiple logistic regression analysis was conducted with the change in diagnosis from non-dementia to dementia at 1 y as the dependent variable. A total of 26 participants (16.0%) were diagnosed as having converted to dementia. Multiple logistic regression analysis revealed that both the qualitative CDT score using Cahn et al.'s scoring system and the existence of conceptual deficits were significantly associated with progression to dementia at 1 y after initial assessment of cognitive function, irrespective of the MMSE score, among non-demented older individuals. The CDT may be a useful predictor of progression to dementia in primary care settings.}, } @article {pmid32894135, year = {2020}, author = {Beckers, LWME and Smeets, RJEM}, title = {Methodological and interpretive concerns about Beemster et al.'s article 'The interpretation of change score of the pain disability index after vocational rehabilitation is baseline dependent': a letter to the editor.}, journal = {Health and quality of life outcomes}, volume = {18}, number = {1}, pages = {301}, pmid = {32894135}, issn = {1477-7525}, mesh = {*Disability Evaluation ; Humans ; Pain ; Pain Measurement ; *Quality of Life ; Rehabilitation, Vocational ; }, abstract = {This is a critique of Beemster et al.'s article 'The interpretation of change score of the pain disability index after vocational rehabilitation is baseline dependent' (2018). The methodological issues in question include the choices of anchor to determine the minimal important change, and the intraclass correlation coefficient on which the calculation of the standard error of measurement was based. We believe these undermine the authors' interpretation.}, } @article {pmid32885234, year = {2021}, author = {Hammers, DB and Porter, S and Dixon, A and Suhrie, KR and Duff, K}, title = {Validating 1-Year Reliable Change Methods.}, journal = {Archives of clinical neuropsychology : the official journal of the National Academy of Neuropsychologists}, volume = {36}, number = {1}, pages = {87-98}, pmid = {32885234}, issn = {1873-5843}, support = {R01 AG055428/AG/NIA NIH HHS/United States ; }, mesh = {Aged ; *Cognition ; *Cognitive Dysfunction/diagnosis ; Humans ; Neuropsychological Tests ; Regression Analysis ; }, abstract = {OBJECTIVE: reliable change methods can assist in the determination of whether observed changes in performance are meaningful. The current study sought to validate previously published 1-year standardized regression-based (SRB) equations for commonly administered neuropsychological measures that incorporated baseline performances, demographics, and 1-week practice effects.

METHOD: Duff et al.'s SRB prediction equations were applied to an independent sample of 70 community-dwelling older adults with either normal cognition or mild cognitive impairment, assessed at baseline, at 1 week, and at 1 year.

RESULTS: minimal improvements or declines were seen between observed baseline and observed 1-year follow-up scores, or between observed 1-year and predicted 1-year scores, on most measures. Relatedly, a high degree of predictive accuracy was observed between observed 1-year and predicted 1-year scores across cognitive measures in this repeated battery.

CONCLUSIONS: these results, which validate Duff et al.'s SRB equations, will permit clinicians and researchers to have more confidence when predicting cognitive performance on these measures over 1 year.}, } @article {pmid32879966, year = {2021}, author = {Kelly, L and Harrison, M and Richardson, N and Carroll, P and Egan, T and Ormond, G and Robertson, S}, title = {Economic evaluation of 'Men on the Move', a 'real world' community-based physical activity programme for men.}, journal = {European journal of public health}, volume = {31}, number = {1}, pages = {156-160}, doi = {10.1093/eurpub/ckaa152}, pmid = {32879966}, issn = {1464-360X}, mesh = {Cost-Benefit Analysis ; *Exercise ; Humans ; Ireland ; Male ; Quality-Adjusted Life Years ; Retrospective Studies ; }, abstract = {BACKGROUND: Physical activity (PA) interventions capable of producing health benefits cost effectively are a public health priority across the Western world. 'Men on the Move' (MOM), a community-based PA intervention for men, demonstrated significant health benefits up to 52-weeks (W) post-baseline. This article details the economic evaluation of MOM with a view to determining its cost-effectiveness as a public health intervention to be rolled out nationally in Ireland.

METHODS: Cost-effectiveness was determined by comparing the costs (direct and indirect) of the programme to its benefits, which were captured as the impact on quality-adjusted life-years (QALYs). For the benefits, cost-utility analysis was conducted by retrospectively adapting various health-related measures of participants to generate health states using Brazier et al.'s (2002) short form-6D algorithm. This in turn allowed for 'utility measures' to be generated, from which QALYs were derived.

RESULTS: Findings show MOM to be cost-effective in supporting an 'at risk' cohort of men achieves significant improvements in aerobic fitness, weight loss and waist reduction. The total cost per participant (€125.82 for each of the 501 intervention participants), the QALYs gained (11.98 post-12-W intervention, or 5.3% health improvement per participant) and estimated QALYs ratio costs of €3723 represents a cost-effective improvement when compared to known QALY guidelines.

CONCLUSIONS: The analysis shows that the cost per QALY achieved by MOM is significantly less than the existing benchmarks of £20 000 and €45 000 in the UK and Ireland respectively, demonstrating MOM to be cost-effective.}, } @article {pmid32867181, year = {2020}, author = {Zhu, F and Li, P and Xu, H and Wang, R}, title = {A Novel Lightweight Authentication Scheme for RFID-Based Healthcare Systems.}, journal = {Sensors (Basel, Switzerland)}, volume = {20}, number = {17}, pages = {}, pmid = {32867181}, issn = {1424-8220}, support = {NY216016//Nanjing University of Posts and Telecommunications/ ; 61902196//National Natural Science Foundation of China/ ; 61872196//National Natural Science Foundation of China/ ; 61602261//National Natural Science Foundation of China/ ; 61672296//National Natural Science Foundation of China/ ; BE2017166//Scientific and Technological Support Project of Jiangsu Province/ ; BE2019740//Scientific and Technological Support Project of Jiangsu Province/ ; 18KJA520008//Major Natural Science Research Projects in Colleges and Universities of Jiangsu Province/ ; RJFW-111//Six Talent Peaks Project of Jiangsu Province/ ; }, mesh = {*Computer Security ; Confidentiality ; Delivery of Health Care ; Humans ; Internet of Things ; Privacy ; *Radio Frequency Identification Device ; *Telemedicine ; }, abstract = {The Internet of Things (IoT) has been integrated into legacy healthcare systems for the purpose of improving healthcare processes. As one of the key technologies of IoT, radio frequency identification (RFID) technology has been applied to offer services like patient monitoring, drug administration, and medical asset tracking. However, people have concerns about the security and privacy of RFID-based healthcare systems, which require a proper solution. To solve the problem, recently in 2019, Fan et al. proposed a lightweight RFID authentication scheme in the IEEE Network. They claimed that their scheme can resist various attacks in RFID systems with low implementation cost, and thus is suitable for RFID-based healthcare systems. In this article, our contributions mainly consist of two parts. First, we analyze the security of Fan et al.'s scheme and find out its security vulnerabilities. Second, we propose a novel lightweight authentication scheme to overcome these security weaknesses. The security analysis shows that our scheme can satisfy the necessary security requirements. Besides, the performance evaluation demonstrates that our scheme is of low cost. Thus, our scheme is well-suited for practical RFID-based healthcare systems.}, } @article {pmid32860512, year = {2020}, author = {Feltmate, BBT and Hurst, AJ and Klein, RM}, title = {Effects of fatigue on attention and vigilance as measured with a modified attention network test.}, journal = {Experimental brain research}, volume = {238}, number = {11}, pages = {2507-2519}, doi = {10.1007/s00221-020-05902-y}, pmid = {32860512}, issn = {1432-1106}, support = {520225-17//Natural Sciences and Engineering Research Council of Canada/ ; }, mesh = {Executive Function ; *Fatigue ; Humans ; Psychomotor Performance ; Reaction Time ; *Wakefulness ; }, abstract = {As part of a larger study on the effects of fatigue on various attentional and behavioural measures, we had participants complete a modified version of Luna et al.'s (J Neurosci Methods 306:77-87, Luna et al., J Neurosci Methods 306:77-87, 2018) ANTI-Vea task (mANTI-Vea) at the beginning and end (pre/post) of each of two 8-h testing sessions. Between these administrations of the mANTI-Vea our participants spent ~ 6 h performing an intervening task. Our intent in this project was two-fold: first, to replicate the pattern of effects reported in Luna et al.'s original presentation of the ANTI-Vea; second, to assay the impact of fatigue on vigilance and attention by observing shifts in mANTI-Vea performance as a function of time on task and before versus after the intervening task. With time-on-task (the mANTI-Vea is divided into six sub-blocks) we observed that participants became increasingly conservative in their biases to respond towards infrequent targets, showed a decline in sensitivity, and lapsed in responding in the psychomotor vigilance task with greater frequency. In the pre/post comparison, we observed an increase in the proportion of lapses, but not in participants' response biases. Attentional network scores were found to be somewhat insensitive to our fatigue manipulations; the effect of time-on-task was only significant for orienting scores on RT, and our pre/post comparison was only significant for RT derived executive functioning scores.}, } @article {pmid32859722, year = {2020}, author = {Quirk, C and Adam, KCS and Vogel, EK}, title = {No Evidence for an Object Working Memory Capacity Benefit with Extended Viewing Time.}, journal = {eNeuro}, volume = {7}, number = {5}, pages = {}, pmid = {32859722}, issn = {2373-2822}, support = {R01 MH087214/MH/NIMH NIH HHS/United States ; }, mesh = {Humans ; *Memory, Short-Term ; Mental Recall ; *Visual Perception ; }, abstract = {Visual working memory is the ability to hold visual information temporarily in mind. A key feature of working memory is its starkly limited capacity, such that only a few simple items can be remembered at once. Prior work has shown that this capacity limit cannot be circumvented by providing additional encoding time, whether providing just 200 ms or up to 1300 ms, capacity is still limited to only three to four items. In contrast, Brady et al. (2016) hypothesized that real-world objects, but not simple items used in prior research, benefit from additional encoding time and are not subject to traditional capacity limits. They supported this hypothesis with results from both behavior and the contralateral delay activity (CDA), an EEG marker of working memory storage, and concluded that familiar, complex stimuli are necessary to observe encoding time effects. Here, we conducted three replications of Brady et al.'s key manipulation with a larger number of human participants and more trials per condition. We failed to replicate their primary behavioral result (objects benefit more than colors from additional encoding time) and failed to observe an object-specific increase in the CDA. Instead, we found that encoding time benefitted both simple color items and real-world objects, in contrast to both the findings by Brady et al., and some prior work on this topic. Overall, we observed no support for the hypothesis that real-world objects have a different capacity than colored squares. We discuss the implications of our findings for theories of visual working memory (VWM).}, } @article {pmid32848897, year = {2020}, author = {Novara, C and Pardini, S and Cardona, F and Pastore, M}, title = {Comparing Models of the Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) in an Italian Clinical Sample.}, journal = {Frontiers in psychiatry}, volume = {11}, number = {}, pages = {615}, pmid = {32848897}, issn = {1664-0640}, abstract = {BACKGROUND: Obsessive-Compulsive Disorder (OCD) is a mental disorder that interferes with daily functioning and may arise during childhood. The current study is the first attempt by Italian researchers to validate the Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS).

AIMS: The study's primary aim was to investigate the best CY-BOCS model fit, adopting a Bayesian model comparison strategy, among four different factor models: a one-factor model; a two-factor model based on Obsessions and Compulsions; Storch et al.'s and Mc Kay et al.'s two-factor model based on Disturbance and Severity. The study also aimed to investigate the types of treatments found in a sample of Italian OCD children patients.

METHODS: The study sample was made up of 53 children with OCD and 14 children with Tourette Syndrome and TIC.

RESULTS: An analysis of our data demonstrated that the Obsessions and Compulsions model was the most plausible one, as it demonstrated the best fit indices, strong convergent validity, and good reliability. The study results additionally uncovered that 24.5% of the children in the OCD sample had not yet begun any treatment pathway a year after a diagnosis was formulated.

CONCLUSIONS: These findings suggest that the Obsessions and Compulsions scales of the CY-BOCS separately represent appropriate instruments to evaluate children with OCD.}, } @article {pmid32845334, year = {2021}, author = {Baker, J and Meade, A and Pagel, M and Venditti, C}, title = {Nothing Wrong with the Analysis of Clades in Comparative Evolutionary Studies: A Reply to Poe et al.}, journal = {Systematic biology}, volume = {70}, number = {1}, pages = {197-201}, pmid = {32845334}, issn = {1076-836X}, mesh = {*Phylogeny ; }, abstract = {In a recent paper, Poe et al. assert that scientists should abandon clade-based approaches, particularly those using named taxonomic ranks. Poe et al. attempt to demonstrate that clade selection can have effects on the results of evolutionary analyses but unfortunately fall short of making any robust conclusions. Here, we demonstrate that the assertions made by Poe et al. have two important flaws: (i) an erroneous view of modern phylogenetic comparative methods; and (ii) a lack of statistical rigor in their analyses. We repeat Poe et al.'s analysis but using appropriate phylogenetic comparative approaches. We demonstrate that results remain consistent regardless of the clade definition. We go on to discuss the value of taxonomic groupings and how they can provide meaningful units of comparison in evolutionary study. Unlike the disheartening suggestion to abandon the use of clades, scientists can instead continue to use phylogenetic " corrections" that are already the standard for most comparative evolutionary analyses. [Comparative methods; evolution; phylogeny; taxonomy.].}, } @article {pmid32845210, year = {2021}, author = {Zhang, J and Zhu, L and Tang, Q}, title = {Electroacupuncture with rehabilitation training for limb spasticity reduction in post-stroke patients: A systematic review and meta-analysis.}, journal = {Topics in stroke rehabilitation}, volume = {28}, number = {5}, pages = {340-361}, doi = {10.1080/10749357.2020.1812938}, pmid = {32845210}, issn = {1945-5119}, mesh = {Activities of Daily Living ; *Electroacupuncture ; Humans ; Muscle Spasticity/etiology ; *Stroke/complications ; *Stroke Rehabilitation ; }, abstract = {OBJECTIVE: To assess the effectiveness of electroacupuncture (EA) with rehabilitation training in reducing limb spasticity in post-stroke patients.

METHODS: A systematic review was performed by electronically searching six databases (Medline/Pubmed, Embase, Cochrane Library, China National Knowledge Infrastructure, Database for Chinese Technical Periodicals, and Wanfang Data) for randomized controlled trials (RCTs) on EA with rehabilitation training for limb spasticity reduction in post-stroke patients from 1 January 2009 to 1 January 2019. A meta-analysis was performed using SAS 9.3 and RevMan 5.3 software after bibliography screening, data extraction, and risk of bias assessment using the Cochrane handbook. The primary outcome was spasticity.

RESULTS: A total of 31 RCTs (including 2488 participants) were included. Except for Cai et al.'s study, the quality of other RCTs was not high. All studies performed a descriptive analysis, and 29 RCTs conducted a meta-analysis. The odds ratio (OR) for marked efficiency was 2.35 (95% confidence interval [CI] 1.68-3.27, Z = 5.03, P < .00001). The OR for Modified Ashworth Scale (MAS) classification was 2.42 (95% CI 1.89-3.10, Z = 7.03; P < .00001). The weighted mean difference (WMD) for MAS score was -0.68 (95% CI -0.79 - -0.56, Z = 11.24, P < .00001). The WMD for clinical spasticity index score was -1.50 (95% CI -2.28 - -0.72, Z = 3.79, P = .0002).

CONCLUSION: EA with rehabilitation training could be a good strategy for reducing limb spasticity after stroke and is better than EA alone or rehabilitation training alone. However, its effectiveness remains to be further verified by large-sample and high-quality RCTs.}, } @article {pmid32838544, year = {2020}, author = {Looi, JC and Allison, S and Bastiampillai, T}, title = {Response to McGorry et al.'s defence of Headspace-like Leviathans swallowing resources.}, journal = {The Australian and New Zealand journal of psychiatry}, volume = {54}, number = {11}, pages = {1059-1060}, doi = {10.1177/0004867420952549}, pmid = {32838544}, issn = {1440-1614}, mesh = {*Health Resources ; }, } @article {pmid32836604, year = {2020}, author = {Xie, S and Li, H}, title = {Accessibility, affordability, accountability, sustainability and social justice of early childhood education in China: A case study of Shenzhen.}, journal = {Children and youth services review}, volume = {118}, number = {}, pages = {105359}, pmid = {32836604}, issn = {0190-7409}, abstract = {This study examined the accessibility, affordability, accountability, sustainability, and social justice of early childhood education (ECE) services in Shenzhen, China, using Li et al.'s (2017) '3A2S' framework. Government documents and secondary data during the past decade were collected and evaluated. The results indicated that: (1) the ECE services have improved in the dimensions of accessibility, affordability, accountability, sustainability, and social justice; (2) more efforts should be made in increasing fiscal budget into ECE services and ensuring the quality of the ECE services; and (3) the government needs to take up more responsibilities to strike a balance between market force and governmental regulation. Implications and suggestions are also included.}, } @article {pmid32831400, year = {2020}, author = {Kang, I and Ratcliff, R and Voskuilen, C}, title = {A Note on Decomposition of Sources of Variability in Perceptual Decision-making.}, journal = {Journal of mathematical psychology}, volume = {98}, number = {}, pages = {}, pmid = {32831400}, issn = {0022-2496}, support = {R01 AG017083/AG/NIA NIH HHS/United States ; R01 AG041176/AG/NIA NIH HHS/United States ; R01 AG057841/AG/NIA NIH HHS/United States ; }, abstract = {Information processing underlying human perceptual decision-making is inherently noisy and identifying sources of this noise is important to understand processing. Ratcliff, Voskuilen, and McKoon (2018) examined results from five experiments using a double-pass procedure in which stimuli were repeated typically a hundred trials later. Greater than chance agreement between repeated tests provided evidence for trial-to-trial variability from external sources of noise. They applied the diffusion model to estimate the quality of evidence driving the decision process (drift rate) and the variability (standard deviation) in drift rate across trials. This variability can be decomposed into random (internal) and systematic (external) components by comparing the double-pass accuracy and agreement with the model predictions. In this note, we provide an additional analysis of the double-pass experiments using the linear ballistic accumulator (LBA) model. The LBA model does not have within-trial variability and thus it captures all variability in processing with its across-trial variability parameters. The LBA analysis of the double-pass data provides model-based evidence of external variability in a decision process, which is consistent with Ratcliff et al.'s result. This demonstrates that across-trial variability is required to model perceptual decision-making. The LBA model provides measures of systematic and random variability as the diffusion model did. But due to the lack of within-trial variability, the LBA model estimated the random component as a larger proportion of across-trial total variability than did the diffusion model.}, } @article {pmid32814485, year = {2022}, author = {Boute, T and Rizzo, G and Mappa, I and Makatsariya, A and Toneto, BR and Moron, AF and Rolo, LC}, title = {Correlation between estimated fetal weight and weight at birth in infants with gastroschisis and omphalocele.}, journal = {The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians}, volume = {35}, number = {16}, pages = {3070-3075}, doi = {10.1080/14767058.2020.1808615}, pmid = {32814485}, issn = {1476-4954}, mesh = {Birth Weight ; Female ; Fetal Growth Retardation ; Fetal Weight ; Fetus ; *Gastroschisis/complications/epidemiology ; Gestational Age ; *Hernia, Umbilical/complications/epidemiology ; Humans ; Infant, Newborn ; Pregnancy ; Retrospective Studies ; Ultrasonography, Prenatal ; }, abstract = {BACKGROUND: An accurate estimated fetal weight (EFW) calculated with traditional formulae in cases of abdominal wall defects (AWDs) can be challenging. As a result of reduced abdominal circumference, fetal weight may be underestimated, which could affect prenatal management. Siemer et al. proposed a formula without the use of abdominal circumference, but it is not used in our protocols yet.

OBJECTIVES: Our aim was to evaluate the correlation of EFW and birth weight in fetuses with AWD by using Hadlock 1, Hadlock 2, and Siemer et al.'s formulae. Our secondary goal was to evaluate how often fetuses classified as small for gestational age (SGA) were in fact SGA at birth.

STUDY DESIGN: This was a retrospective cohort study of gestations complicated by gastroschisis and omphalocele at two tertiary-care centers in Brazil and Italy during an 8-year period. Of a total of 114 cases, 85 (44 cases of gastroschisis and 41 cases of omphalocele) met our criteria.

RESULTS: The last prenatal scan was performed 5.2 (±4.1) days before birth. The mean gestational age at birth was 37.2 (±1.8) weeks. Correlation of EFW with birth weight was calculated with the three formulae with and without adjustment for weight gain between scan and birth, with the use of the Spearman coefficient. The correlation between EFW and weight at birth was positive according to all three formulae for the infants with gastroschisis. This finding was not confirmed in the infants with omphalocele. All formulae overestimated the number of SGA cases: although only 17.6% of fetuses were actually SGA at birth, the Hadlock formulae had classified nearly 35% of them as SGA, and Siemer et al.'s formula, 15.3%.

CONCLUSION: All three formulae yielded a good correlation between EFW in the last scan and birth weight in the infants with gastroschisis but not for those with omphalocele. Cases of SGA were overestimated.}, } @article {pmid32811517, year = {2020}, author = {Khadjesari, Z and Boufkhed, S and Vitoratou, S and Schatte, L and Ziemann, A and Daskalopoulou, C and Uglik-Marucha, E and Sevdalis, N and Hull, L}, title = {Implementation outcome instruments for use in physical healthcare settings: a systematic review.}, journal = {Implementation science : IS}, volume = {15}, number = {1}, pages = {66}, pmid = {32811517}, issn = {1748-5908}, support = {/DH_/Department of Health/United Kingdom ; }, mesh = {*Checklist ; *Delivery of Health Care ; Health Facilities ; Humans ; Psychometrics ; Reproducibility of Results ; }, abstract = {BACKGROUND: Implementation research aims to facilitate the timely and routine implementation and sustainment of evidence-based interventions and services. A glaring gap in this endeavour is the capability of researchers, healthcare practitioners and managers to quantitatively evaluate implementation efforts using psychometrically sound instruments. To encourage and support the use of precise and accurate implementation outcome measures, this systematic review aimed to identify and appraise studies that assess the measurement properties of quantitative implementation outcome instruments used in physical healthcare settings.

METHOD: The following data sources were searched from inception to March 2019, with no language restrictions: MEDLINE, EMBASE, PsycINFO, HMIC, CINAHL and the Cochrane library. Studies that evaluated the measurement properties of implementation outcome instruments in physical healthcare settings were eligible for inclusion. Proctor et al.'s taxonomy of implementation outcomes was used to guide the inclusion of implementation outcomes: acceptability, appropriateness, feasibility, adoption, penetration, implementation cost and sustainability. Methodological quality of the included studies was assessed using the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) checklist. Psychometric quality of the included instruments was assessed using the Contemporary Psychometrics checklist (ConPsy). Usability was determined by number of items per instrument.

RESULTS: Fifty-eight publications reporting on the measurement properties of 55 implementation outcome instruments (65 scales) were identified. The majority of instruments assessed acceptability (n = 33), followed by appropriateness (n = 7), adoption (n = 4), feasibility (n = 4), penetration (n = 4) and sustainability (n = 3) of evidence-based practice. The methodological quality of individual scales was low, with few studies rated as 'excellent' for reliability (6/62) and validity (7/63), and both studies that assessed responsiveness rated as 'poor' (2/2). The psychometric quality of the scales was also low, with 12/65 scales scoring 7 or more out of 22, indicating greater psychometric strength. Six scales (6/65) rated as 'excellent' for usability.

CONCLUSION: Investigators assessing implementation outcomes quantitatively should select instruments based on their methodological and psychometric quality to promote consistent and comparable implementation evaluations. Rather than developing ad hoc instruments, we encourage further psychometric testing of instruments with promising methodological and psychometric evidence.

PROSPERO 2017 CRD42017065348.}, } @article {pmid32803604, year = {2020}, author = {Pickson, RB and He, G and Ntiamoah, EB and Li, C}, title = {Cereal production in the presence of climate change in China.}, journal = {Environmental science and pollution research international}, volume = {27}, number = {36}, pages = {45802-45813}, pmid = {32803604}, issn = {1614-7499}, mesh = {Carbon Dioxide/analysis ; China ; *Climate Change ; Economic Development ; *Edible Grain/chemistry ; }, abstract = {This study sought to investigate the impacts of climate change on cereal production in China over the period 1990Q1-2013Q4. Using the Autoregressive Distributed Lag (ARDL) approach, the results showed that CO2 emissions, average temperature, and temperature variability have a significant negative impact on cereal production in the long run. However, energy consumption, average rainfall, labor force, and cultivated area significantly and positively influenced the production of cereal crops in the long run. Meanwhile, the study observed that rainfall variability has no significant effect on cereal production in the long run. The study again found that in the short run, CO2 emissions, average temperature, and temperature variability have a significant negative relationship with cereal production. Besides, energy consumption, average rainfall, rainfall variability, labor force, and the cultivated area had a significant positive association with cereal production in the short run. The results of the Granger causality test showed that there exists a unidirectional causality running from CO2 emissions, energy consumption, and labor force to the production of cereal crops in China. On the contrary, the study found no causality between cultivated area and cereal production. The study suggests that improved cereal crop varieties ought to be developed and introduced to cope with the adverse impacts of climate change in China. This will help to circumvent Huang et al.'s (2017) prediction of a decline in the total food self-sufficiency of China from 94.5% in 2015 to about 91% by 2025.}, } @article {pmid32800433, year = {2020}, author = {DiMarco, M}, title = {(re)Producing mtEve.}, journal = {Studies in history and philosophy of biological and biomedical sciences}, volume = {83}, number = {}, pages = {101290}, doi = {10.1016/j.shpsc.2020.101290}, pmid = {32800433}, issn = {1879-2499}, mesh = {Africa ; *DNA, Mitochondrial ; *Evolution, Molecular ; Female ; Humans ; *Phylogeny ; }, abstract = {In their 1987 Nature publication, "Mitochondrial DNA and Human Evolution," Rebecca Cann, Mark Stoneking, and Allan C. Wilson gave a new reconstruction of human evolution on the basis of differences in mitochondrial DNA among contemporary human populations. This phylogeny included an African common ancestor for all human mitochondrial DNA (mtDNA) lineages, and Cann et al.'s reconstruction became known as the "Out of Africa" hypothesis. Since mtDNA is inherited exclusively through the maternal line, the common ancestor who was first branded African Eve later became known as Mitochondrial Eve (mtEve, for short). In this paper, I show that mtEve was not a single, successful, or purely scientific discovery. Instead, she was produced many times and in many ways, each of which informed the next. Importantly, though Wilson and colleagues heralded mitochondrial DNA as a source of certainty, objectivity, and consensus for evolutionary inference, their productions of Mitochondrial Eve depended as much on popular assumptions about the certainty of maternal inheritance as they did on new molecular and computational tools. This recognition lets us reevaluate the complex consequences of these productions, which, like mtEve herself, could not be confined to a purely social, material, or scientific dimension.}, } @article {pmid32787828, year = {2020}, author = {Su, Q and Li, C and Li, Y and Zhou, Z and Zhang, S and Guo, S and Feng, X and Yan, M and Zhang, Y and Zhang, J and Pan, J and Cheng, B and Tan, J}, title = {Analysis and improvement of the three-column spinal theory.}, journal = {BMC musculoskeletal disorders}, volume = {21}, number = {1}, pages = {537}, pmid = {32787828}, issn = {1471-2474}, support = {2017YFA0105404//Multicenter Clinical Trial of hUC-MSCs in the Treatment of Late Chronic Spinal Cord Injury/ ; 81972095//National Natural Science Foundation of China/ ; 19441901702//Project of Shanghai Science and Technology Commission/ ; }, mesh = {Adult ; Fracture Fixation, Internal ; Humans ; Lumbar Vertebrae/diagnostic imaging/injuries ; Male ; Middle Aged ; Retrospective Studies ; *Spinal Fractures/diagnostic imaging/epidemiology ; *Thoracic Vertebrae/diagnostic imaging/injuries ; }, abstract = {BACKGROUND: Denis and Ferguson et al.'s three-column spinal theory has been widely accepted and applied. However, this three-column theory was proposed based solely on observation and experience without thorough documented data and analysis. The aim of this study was to analyze and improve Denis and Ferguson et al.'s three-column spinal theory to propose a novel three-column concept in epidemiology, morphology and biomechanics.

METHODS: A retrospective analysis of the computed tomography imaging data of patients with a diagnosis of T11-L5 vertebral fractures was conducted between February 2010 and December 2018. Three-dimensional (3D) distribution maps of fracture lines of all subjects were obtained based on 3D mapping techniques. In addition, a 25-year-old health male volunteer was recruited for the vertebral finite element force analysis.

RESULTS: The present study enrolled 459 patients (age: 48 ± 11.42 years), containing a total of 521 fractured vertebrae. The fracture lines peaked in the upper and the outer third sections of the vertebra, starting from the anterior part of the vertebral pedicles in 3-D maps. Regarding flexion and extension of the spine, the last third of the vertebral body in front of the spinal canal was one main stress center in the finite element analysis. The stress on the vertebral body was greater in front of the pedicles in the lateral bending.

CONCLUSION: The study reveals that the posterior one-third of the vertebral body in front of the spinal canal and the posterior one-third of the vertebral body in front of the pedicle are very different in terms of fracture characteristics and risks to spinal canal (3D maps and stress distributing graphs), therefore, they should be classified as different columns. We provide strong evidence that Su's three-column theory complies with the characteristics of vertebral physiological structure, vertebral fracture, and vertebral biomechanics.}, } @article {pmid32784520, year = {2020}, author = {Hew-Butler, T and Smith-Hale, V and Van Sumeren, M and Sabourin, J and Levy, P}, title = {Is Exercise the Best Medicine during a COVID-19 Pandemic? Comment on Constandt, B.; Thibaut, E.; De Bosscher, V.; Scheerder, J.; Ricour, M.; Willem, A. Exercising in Times of Lockdown: An Analysis of the Impact of COVID-19 on Levels and Patterns of Exercise among Adults in Belgium. Int. J. Environ. Res. Public Health 2020, 17, 4144.}, journal = {International journal of environmental research and public health}, volume = {17}, number = {16}, pages = {}, pmid = {32784520}, issn = {1660-4601}, mesh = {Adult ; Belgium ; *Betacoronavirus ; COVID-19 ; Coronavirus Infections/*epidemiology ; Humans ; *Pandemics ; *Pneumonia, Viral ; Public Health ; SARS-CoV-2 ; }, abstract = {From Constandt et al.'s survey of 13,515 Belgium respondents, regular physical activity can be successfully initiated and sustained during a lockdown, with appropriate social distancing measures. Documentation that 77% of highly active people and 58% of low active people exercised as much or more following the institution of a nationwide lockdown was impressive, given that the cases of COVID-19 were accelerating at that time. The Belgian government's central promotion of exercise, to boost both the mental and physical health of the population, likely contributed to the health, tolerance, and ultimate success of lockdown. In this commentary, we wish to pose a follow-up query which highlights the potential detrimental effects of intense exercise (competition) performed without social distancing measures. The proposed graphical abstract elucidates these possible risks, in contrast to the favorable results outlined in Constandt et al.'s study.}, } @article {pmid32780670, year = {2021}, author = {Brewin, CR}, title = {Tilting at Windmills: Why Attacks on Repression Are Misguided.}, journal = {Perspectives on psychological science : a journal of the Association for Psychological Science}, volume = {16}, number = {2}, pages = {443-453}, pmid = {32780670}, issn = {1745-6924}, mesh = {Humans ; *Memory ; *Repression, Psychology ; }, abstract = {In the November 2019 issue of Perspectives, Otgaar et al. argued that the "memory wars" persist and that "the controversial issue of repressed memories is alive and well and may even be on the rise" (p. 1072). Their thesis overlooked the well-established consensus that recovered memories of trauma may be genuine, false, or a mixture of the two and instead focused on a disputed mechanism: unconscious repression. A formal cocitation analysis identified the major publications mentioning repressed memories, but none endorsed a theory of unconscious repression. Studies of beliefs about repressed memories by the general public and other groups do not support Otgaar et al.'s thesis either because these studies did not adequately assess the key ideas defining the theory of repression. Clinical evidence is consistent with recovered memories occurring in many different forms of therapy, including ones that do not use suggestive techniques or rely on the concept of repression. Thus, Otgaar et al. have proposed the existence of a problem for which little objective evidence can be found. Continuing theoretical uncertainties about the mechanisms responsible for forgetting are less important than the general recognition since the 1990s that suggestive therapy and attempts to exhume memories are hazardous and generally inappropriate.}, } @article {pmid32757591, year = {2020}, author = {Lupker, SJ and Spinelli, G and Davis, CJ}, title = {Is zjudge a better prime for JUDGE than zudge is?: A new evaluation of current orthographic coding models.}, journal = {Journal of experimental psychology. Human perception and performance}, volume = {46}, number = {11}, pages = {1252-1266}, doi = {10.1037/xhp0000856}, pmid = {32757591}, issn = {1939-1277}, support = {//Economic and Social Research Council/ ; //Natural Sciences and Engineering Research Council/ ; }, mesh = {Adult ; Decision Making/physiology ; Female ; Humans ; Male ; Pattern Recognition, Visual/*physiology ; Perceptual Masking/*physiology ; *Psycholinguistics ; *Reading ; Recognition, Psychology/*physiology ; Young Adult ; }, abstract = {Three masked priming paradigms, the conventional masked priming lexical-decision task (Forster & Davis, 1984), the sandwich priming task (Lupker & Davis, 2009), and the masked priming same-different task (Norris & Kinoshita, 2008), were used to investigate priming for a given target (e.g., JUDGE) from primes created by either adding a letter to the beginning of the target (e.g., zjudge) or replacing the target's initial letter (e.g., zudge). Virtually all models of orthographic coding that allow calculation of orthographic similarity measures predict that zjudge should be the better prime because zjudge contains all the letters in JUDGE in their correct order whereas zudge does not. Nonetheless, Adelman et al.'s (2014) megastudy data indicated no difference in the effectiveness of these two prime types. The present experiments provide additional support for the conclusion of no difference between these two prime types with the only observed difference being a small zudge prime advantage in Experiment 1b (sandwich priming). These results suggest that models of orthographic coding/word recognition may be well served by allowing inconsistent information (e.g., the "z" in both zjudge and zudge indicates that the presented prime is not JUDGE) to be given considerable weight during the orthographic coding/word recognition process. (PsycInfo Database Record (c) 2020 APA, all rights reserved).}, } @article {pmid32750829, year = {2022}, author = {Pan, X and Zhang, M and Ding, D and Yang, M}, title = {A Geometrical Perspective on Image Style Transfer With Adversarial Learning.}, journal = {IEEE transactions on pattern analysis and machine intelligence}, volume = {44}, number = {1}, pages = {63-75}, doi = {10.1109/TPAMI.2020.3011143}, pmid = {32750829}, issn = {1939-3539}, abstract = {Recent years witness the booming trend of applying generative adversarial nets (GAN) and its variants to image style transfer. Although many reported results strongly demonstrate the power of GAN on this task, there is still little known about neither the interpretations of several fundamental phenomenons of image style transfer by generative adversarial learning, nor its underlying mechanism. To bridge this gap, this paper presents a general framework for analyzing style transfer with adversarial learning through the lens of differential geometry. To demonstrate the utility of our proposed framework, we provide an in-depth analysis of Isola et al.'s pioneering style transfer model pix2pix [1] and reach a comprehensive interpretation on their major experimental phenomena. Furthermore, we extend the notion of generalization to conditional GAN and derive a condition to control the generalization capability of the pix2pix model. From a higher viewpoint, we further prove a learning-free condition to guarantee the existence of infinitely many perfect style transfer mappings. Besides, we also provide a number of practical suggestions on model design and dataset construction based on these derived theoretical results to facilitate further researches.}, } @article {pmid32740560, year = {2020}, author = {Spielmans, GI and Rosen, GM and Spence-Sing, T}, title = {Tapping Away at a Misleading Meta-analysis: No Evidence for Specificity of Acupoint Tapping.}, journal = {The Journal of nervous and mental disease}, volume = {208}, number = {8}, pages = {628-631}, doi = {10.1097/NMD.0000000000001181}, pmid = {32740560}, issn = {1539-736X}, mesh = {*Acupuncture Points ; *Acupuncture Therapy ; Freedom ; Humans ; }, abstract = {Church et al.'s meta-analysis of three studies claimed to support the specificity of acupoint tapping as a therapeutic technique in the treatment of mental health problems. However, our critical analysis found substantial methodological problems and inaccurate statistical analyses, which render their results invalid. Specifically, 1) two included studies did not include participants with documented mental health problems; 2) two included studies did not specifically isolate the effect of acupoint tapping; 3) clear rationales for selected measures were not provided; 4) comparison groups were not bona fide therapies; 5) researcher and therapist allegiances were not controlled; and 6) selection of included studies may have been biased. Further, our attempt to replicate their results failed; we found that acupoint tapping fared no better than comparison groups: k = 3 studies, d = -0.38 (95% confidence interval, 0.10 to -0.87), p = 0.12. We conclude that the Church et al.'s meta-analysis actually found no specific mental health benefits for acupoint tapping.}, } @article {pmid32725769, year = {2020}, author = {Schulte, EM and Wadden, TA and Allison, KC}, title = {An evaluation of food addiction as a distinct psychiatric disorder.}, journal = {The International journal of eating disorders}, volume = {53}, number = {10}, pages = {1610-1622}, doi = {10.1002/eat.23350}, pmid = {32725769}, issn = {1098-108X}, mesh = {Diagnostic and Statistical Manual of Mental Disorders ; Female ; Food Addiction/*diagnosis ; Humans ; Male ; Mental Disorders/*diagnosis ; Reproducibility of Results ; }, abstract = {OBJECTIVE: To evaluate the state of the literature for whether food addiction may warrant consideration as a distinct psychiatric disorder in the Diagnostic and Statistical Manual (DSM) using Blashfield et al.'s (1990; Comprehensive Psychiatry, 31(1), 15-19) five criteria. This framework was utilized because it has recently been applied to examine the diagnostic utility of several eating disorder phenotypes. The criteria are: (a) at least 50 journal articles published on the proposed syndrome in the past 10 years; (b) proposal of diagnostic criteria and assessment measures; (c) clinician reliability in diagnosis; (d) cohesiveness of the proposed diagnostic criteria; and (e) differentiation from similar, existing diagnostic categories.

METHOD: For each criterion, a literature review was conducted to examine if the minimum qualification had been met, and key findings were discussed.

RESULTS: Two of the criteria (literature and differentiation) have been empirically supported to extent specified. Two criteria (diagnostic criteria and syndrome) have been partially fulfilled, due to only having self-report assessment measures and no examination of the odds ratios for meeting more than one symptom, respectively. Clinician reliability has not yet been evaluated.

DISCUSSION: The existing literature suggests that food addiction may warrant consideration as a proposed diagnostic category in the DSM, though future research is needed to fulfill Blashfield et al.'s (1990; Comprehensive Psychiatry, 31(1), 15-19) criteria. The development of a semi-structured interview would be an impactful contribution for addressing these gaps.}, } @article {pmid32722944, year = {2022}, author = {Mirnics, Z and Hittner, JB and Swickert, R and Kövi, Z}, title = {Gratitude and social support mediate the association between mindfulness and mood: A cross-cultural replication study.}, journal = {Journal of health psychology}, volume = {27}, number = {1}, pages = {246-252}, doi = {10.1177/1359105320946389}, pmid = {32722944}, issn = {1461-7277}, mesh = {Affect ; Cross-Cultural Comparison ; Humans ; *Mindfulness ; Social Support ; Surveys and Questionnaires ; Young Adult ; }, abstract = {Swickert and colleagues surveyed young adults in the United States and found that gratitude and social support mediated the association between mindfulness and mood (both positive and negative affect). This study attempted to replicate Swickert et al.'s mediational findings using a young adult Hungarian sample. Results indicated that with one exception, the mediational findings were replicated. The exception was that for the Hungarians, gratitude did not mediate the association between mindfulness and negative affect. Overall, these findings indicate that the mediational effects of gratitude and social support are quite similar for individuals living in the United States and Hungary.}, } @article {pmid32719275, year = {2020}, author = {Azeem, MS and Yesupatham, ST and Mohiyuddin, SMA and Sumanth, V and Ravishankar, S}, title = {Usefulness of salivary sialic acid as a tumor marker in tobacco chewers with oral cancer.}, journal = {Journal of cancer research and therapeutics}, volume = {16}, number = {3}, pages = {605-611}, doi = {10.4103/jcrt.JCRT_337_19}, pmid = {32719275}, issn = {1998-4138}, mesh = {Adult ; Biomarkers, Tumor/metabolism ; Case-Control Studies ; Female ; Humans ; Male ; Middle Aged ; Mouth Neoplasms/chemically induced/diagnosis/*metabolism/pathology ; N-Acetylneuraminic Acid/*metabolism ; Precancerous Conditions/chemically induced/diagnosis/*metabolism/pathology ; Saliva/chemistry/*metabolism ; Squamous Cell Carcinoma of Head and Neck/etiology/*metabolism/pathology ; Tobacco Use/*adverse effects/*metabolism/pathology ; }, abstract = {AIM: This study aims to assess the usefulness of salivary sialic acid (SA) as a tumor marker in the detection of oral squamous cell carcinoma (OSCC) among tobacco chewers.

MATERIALS AND METHODS: After the approval of study protocol by the Institutional Ethics Committee and informed voluntary consent, salivary samples were collected from 96 participants in each group of tobacco chewers with OSCC, tobacco chewers without precancerous or cancerous lesion, and healthy controls. Salivary protein-bound SA (PBSA) and salivary-free SA (FSA) were measured by Yao et al.'s method of acid ninhydrin reaction, and the data were subjected to appropriate statistical analysis.

RESULTS: The salivary PBSA and FSA levels in the Groups 1, 2, and 3 participants were 31.17 ± 7.6 mg/dL and 63.45 ± 9.8 mg/dL, 25.45 ± 16.61 mg/dL and 33.18 ± 11.38 mg/dL, and 22.73 ± 3.01 mg/dL and 21.62 ± 8.86 mg/dL, respectively. Salivary FSA levels were significantly increased among the tobacco chewers with OSCC patients (Group 1) and tobacco chewers with no premalignant lesions of the oral cavity (Group 2) compared to the healthy controls (Group 3) with P < 0.05 being statistically significant. Salivary FSA levels were significantly increased in Group 1 as compared with Group 2. The salivary PBSA was high among Group 1 as compared to the control Group 3; there was however no significant difference in the levels of salivary PBSA between Group 1 and Group 2. There was no significant difference in the PBSA levels between OSCC patients of Group 1 and the tobacco chewers without precancerous or cancerous lesion in the oral cavity of Group 2.

CONCLUSION: Salivary PBSA and FSA are significantly raised in both tobacco chewers with OSCC and in tobacco chewers with no precancerous or cancerous lesions in the oral cavity. SA should therefore be used cautiously while considering it as a marker for the early detection of oral cancer. Tobacco can be a crucial confounding factor when SA is used as a biomarker in OSCC since their levels are elevated to some extent even in tobacco chewers without any clinically obvious precancerous or cancerous lesions in the oral cavity.}, } @article {pmid32692895, year = {2021}, author = {Kikuchi, Y and Umezaki, T and Adachi, K and Sawatsubashi, M and Taura, M and Yamaguchi, Y and Tsuchihashi, N and Murakami, D and Nakagawa, T}, title = {Awareness of stuttering in Japanese children aged 3-7 years.}, journal = {Pediatrics international : official journal of the Japan Pediatric Society}, volume = {63}, number = {2}, pages = {150-153}, doi = {10.1111/ped.14405}, pmid = {32692895}, issn = {1442-200X}, support = {19dk0310102j0001//Japan Agency for Medical Research and Development (AMED)/ ; 19GC1001//Health and Labor Sciences Research Grants/ ; 17K16922//Grant-in-Aid for Young Scientists (B)/ ; }, mesh = {Child ; Child, Preschool ; Humans ; Infant, Newborn ; Japan/epidemiology ; Parents ; Speech ; Speech Disorders ; *Stuttering/diagnosis/epidemiology ; }, abstract = {BACKGROUND: Boey et al. (2009) devised a questionnaire for measuring children's awareness of stuttering and showed that even very young children were often aware of their stuttering. There has been no replication of studies using Boey et al.'s parent-reported questionnaire. The aim of this study was to test whether using Boey et al.'s seven questions, developed for a Dutch speaking population could be effective for measuring the awareness of stuttering in Japanese children.

METHODS: Participants were 54 children who stutter (CWS) aged 3-7 years. Parents answered seven questions about their child's awareness of stuttering according to the questions developed Boey et al. RESULTS: Parental-reported observations of the child responses citing at least one awareness incident were 76%. The percentage of stuttering children with awareness of their own speech difficulties, according to chronological age, were as follows: 70% at age 3 years; 67% at age 4 years; 75% at age 5 years; 81% at age 6 years; and 90% at age 7 years.

CONCLUSIONS: We found that even at age 3 years, many CWS were already aware of their stuttering. The similarity of the data with the seminal study by Boey et al. suggests that the question-based assessment is reproducible even in a country with a different spoken language. The seven questions in Boey et al. are useful for evaluating whether children's awareness of stuttering could contribute to a clinical decision as well as stuttering severity.}, } @article {pmid32687105, year = {2020}, author = {Hamid, M and Akhtar, MI and Ahmed, S}, title = {In response to letter title "Immediate hemodynamic and gaseous exchange effect of bi-level positive airway pressure after cardiac surgery: Our insight to Hamid et al.'s study".}, journal = {Annals of cardiac anaesthesia}, volume = {23}, number = {3}, pages = {373-374}, pmid = {32687105}, issn = {0974-5181}, mesh = {*Cardiac Surgical Procedures ; Gases ; Heart ; Hemodynamics ; Humans ; *Noninvasive Ventilation ; }, } @article {pmid32687104, year = {2020}, author = {R Karim, HM and Gonçalves, G and Esquinas, AM}, title = {Immediate hemodynamic and gaseous exchange; effect of Bi-Level positive airway pressure after cardiac surgery: Our insight to Hamid et al.'s study.}, journal = {Annals of cardiac anaesthesia}, volume = {23}, number = {3}, pages = {372}, pmid = {32687104}, issn = {0974-5181}, mesh = {*Cardiac Surgical Procedures ; Gases ; Heart ; Hemodynamics ; Humans ; *Noninvasive Ventilation ; }, } @article {pmid32677215, year = {2019}, author = {Dardas, LA}, title = {Family functioning moderates the impact of depression treatment on adolescents' suicidal ideations.}, journal = {Child and adolescent mental health}, volume = {24}, number = {3}, pages = {251-258}, doi = {10.1111/camh.12323}, pmid = {32677215}, issn = {1475-357X}, abstract = {PURPOSE: The purpose of this study was to explore whether adolescent-perceived family functioning moderates the depression treatment effects on suicidal ideations.

METHODS: This is a nonpreregistered exploratory secondary analysis of the TADS RCT, which included four treatment groups: fluoxetine, CBT, their combination, and placebo. A random coefficients regression model with posteriori CONTRAST statements was conducted to examine the effects of depression treatment on adolescents' suicidal ideations over time (N = 439). Baron and Kenny's (1986) and Kraemer et al.'s (2002) approach was followed to explore family functioning as a potential moderator of the treatment effects on suicidal ideations over time.

RESULTS: Adolescents in the four treatment groups did not differ significantly in their suicidal ideations at initial status; however, those in the combination group had faster reduction in suicidality. Family functioning moderated the relationship between depression treatment and adolescents' suicidal ideations. In particular, the results revealed that for adolescents who reported positive family functioning (n = 249), treatment had a significant impact on their suicidal ideations over time. However, for adolescents who reported negative family functioning (n = 190), type of treatment did not have a differential effect on improvement in severity of suicidal ideation over time.

CONCLUSION: Findings provided evidence that the process by which depression treatment impacts adolescents' suicidality is contingent upon their family environment. Family-centered approaches to adolescent depression treatment are recommended.}, } @article {pmid32674284, year = {2020}, author = {Chung, KL and Chan, TH and Chen, SN}, title = {Effective Three-Stage Demosaicking Method for RGBW CFA Images Using The Iterative Error-Compensation Based Approach.}, journal = {Sensors (Basel, Switzerland)}, volume = {20}, number = {14}, pages = {}, pmid = {32674284}, issn = {1424-8220}, abstract = {As the color filter array (CFA)2.0, the RGBW CFA pattern, in which each CFA pixel contains only one R, G, B, or W color value, provides more luminance information than the Bayer CFA pattern. Demosaicking RGBW CFA images I R G B W is necessary in order to provide high-quality RGB full-color images as the target images for human perception. In this letter, we propose a three-stage demosaicking method for I R G B W . In the first-stage, a cross shape-based color difference approach is proposed in order to interpolate the missing W color pixels in the W color plane of I R G B W . In the second stage, an iterative error compensation-based demosaicking process is proposed to improve the quality of the demosaiced RGB full-color image. In the third stage, taking the input image I R G B W as the ground truth RGBW CFA image, an I R G B W -based refinement process is proposed to refine the quality of the demosaiced image obtained by the second stage. Based on the testing RGBW images that were collected from the Kodak and IMAX datasets, the comprehensive experimental results illustrated that the proposed three-stage demosaicking method achieves substantial quality and perceptual effect improvement relative to the previous method by Hamilton and Compton and the two state-of-the-art methods, Kwan et al.'s pansharpening-based method, and Kwan and Chou's deep learning-based method.}, } @article {pmid32667374, year = {2020}, author = {Lopez, CG and Horkay, F and Mussel, M and Jones, RL and Richtering, W}, title = {Screening lengths and osmotic compressibility of flexible polyelectrolytes in excess salt solutions.}, journal = {Soft matter}, volume = {16}, number = {31}, pages = {7289-7298}, pmid = {32667374}, issn = {1744-6848}, support = {Z01 HD008756/ImNIH/Intramural NIH HHS/United States ; }, abstract = {We report results of small angle neutron scattering measurements made on sodium polystyrene sulfonate in aqueous salt solutions. The correlation length (ξ) and osmotic compressibility are measured as a function of polymer (c) and added salt (cS) concentrations, and the results are compared with scaling predictions and the random-phase approximation (RPA). In Dobrynin et al.'s scaling model the osmotic pressure consists of a counter-ion contribution and a polymer contribution. The polymer contribution is found to be two orders of magnitude smaller than expected from the scaling model, in agreement with earlier observations made on neutral polymers in good solvent condition. RPA allows the determination of single-chain dimensions in semidilute solutions at high polymer and added salt concentrations, but fails for cS≤ 2 M. The χ parameter can be modelled as the sum of an intrinsic contribution (χ0) and an electrostatic term: χ∼χ0 + K'/√cS, where χ0 > 0.5 is consistent with the hydrophobic nature of the backbone of NaPSS. The dependence of χelec∼ 1/√cS disagrees with the random-phase approximation (χelec∼ 1/cs), but agrees with the light scattering results in dilute solution and Dobrynin et al.'s scaling treatment of electrostatic excluded volume.}, } @article {pmid32663055, year = {2020}, author = {Sherman, SM and Grange, JA}, title = {Exploring the Impact of Mindfulness on False-Memory Susceptibility.}, journal = {Psychological science}, volume = {31}, number = {8}, pages = {968-977}, pmid = {32663055}, issn = {1467-9280}, mesh = {Adolescent ; Adult ; *Attention ; Double-Blind Method ; Female ; Humans ; Male ; *Mental Recall ; *Mindfulness ; Models, Psychological ; Psychological Tests ; *Recognition, Psychology ; Task Performance and Analysis ; Young Adult ; }, abstract = {Wilson, Mickes, Stolarz-Fantino, Evrard, and Fantino (2015) presented data from three well-powered experiments suggesting that a brief mindfulness induction can increase false-memory susceptibility. However, we had concerns about some of the methodology, including whether mind wandering is the best control condition for brief mindfulness inductions. Here, we report the findings from a preregistered double-blind randomized controlled trial designed to replicate and extend Wilson et al.'s findings. Participants (N = 287) underwent 15-min mindfulness or mind-wandering inductions or completed a join-the-dots task before being presented with lists of words related to nonpresented critical lures. This was followed by free-recall and recognition tasks. There was no evidence for an effect of state of mind on correct or false recall or recognition. Furthermore, manipulation checks revealed that mindfulness and mind-wandering inductions activated overlapping states of mind. Exploratory analyses provided some support for mindfulness increasing false memory, but it appears that mind wandering may not be the right control for brief mindfulness research.}, } @article {pmid32657520, year = {2020}, author = {Garg, KK and Agarwal, A and Shamshery, C}, title = {Regarding Samolsky Dekel et al.'s "Reliability of the Buttock Applied Strain Test to Diagnose Radicular Pain in Patients With Low Back Pain".}, journal = {Pain practice : the official journal of World Institute of Pain}, volume = {20}, number = {8}, pages = {950}, doi = {10.1111/papr.12939}, pmid = {32657520}, issn = {1533-2500}, mesh = {Buttocks ; Humans ; *Low Back Pain/diagnosis ; *Radiculopathy/diagnosis ; Reproducibility of Results ; }, } @article {pmid32653728, year = {2020}, author = {Scott, RM and Roby, E and Setoh, P}, title = {2.5-year-olds succeed in identity and location elicited-response false-belief tasks with adequate response practice.}, journal = {Journal of experimental child psychology}, volume = {198}, number = {}, pages = {104890}, doi = {10.1016/j.jecp.2020.104890}, pmid = {32653728}, issn = {1096-0457}, mesh = {Child Development/*physiology ; Child, Preschool ; Comprehension/*physiology ; Female ; Humans ; Male ; *Practice, Psychological ; Thinking/*physiology ; }, abstract = {Researchers have argued that traditional elicited-response false-belief tasks involve considerable processing demands and hence underestimate children's false-belief understanding. Consistent with this claim, Setoh et al. (2016) recently found that when processing demands were sufficiently reduced, children could succeed in an elicited-response task as early as 2.5 years of age. Here we examined whether 2.5-year-olds could also succeed in a low-demand elicited-response task involving false beliefs about identity, which have been argued to provide a critical test of whether children truly represent beliefs, while also clarifying how the practice trials in Setoh et al.'s task facilitated children's elicited-response performance. 2.5-year-olds were tested in a version of Setoh et al.'s elicited-response task in which they heard a location or identity false-belief story. We varied whether the practice trials had the same type of wh-question as the test trial. Children who heard the same type of wh-question on all trials succeeded regardless of which story they heard (location or identity) and performance did not differ across belief type. This replicates Setoh et al.'s positive results and demonstrates that when processing demands are sufficiently reduced, children can succeed in elicited-response tasks involving false beliefs about object location or identity. This suggests that children are capable of attributing genuine false beliefs prior to 4 years of age. However, children performed at chance if the practice trials involved a different type of wh-question than the test trials, suggesting that at this age practice with the wh-question used in the test trial is essential to children's success.}, } @article {pmid32645798, year = {2020}, author = {O'Brien, B and Rutt, JL and Atance, CM}, title = {Are all distances created equal? Insights from developmental psychology.}, journal = {The Behavioral and brain sciences}, volume = {43}, number = {}, pages = {e140}, doi = {10.1017/S0140525X19003078}, pmid = {32645798}, issn = {1469-1825}, mesh = {Brain ; Child ; Humans ; Problem Solving ; *Psychology, Developmental ; }, abstract = {Gilead et al.'s theory presupposes that traversing temporal, spatial, social, and hypothetical distances are largely interchangeable acts of mental travel that co-occur in human ontogeny. Yet, this claim is at odds with recent developmental data suggesting that children's reasoning is differentially affected by the dimension which they must traverse, and that different representational abilities underlie travel across different dimensions.}, } @article {pmid32645795, year = {2020}, author = {Belmonte, MK}, title = {Other and other waters in the river: Autism and the futility of prediction.}, journal = {The Behavioral and brain sciences}, volume = {43}, number = {}, pages = {e122}, doi = {10.1017/S0140525X19003194}, pmid = {32645795}, issn = {1469-1825}, mesh = {*Autistic Disorder ; Brain ; Humans ; Medical Futility ; Rivers ; }, abstract = {Autism has been described as a neural deficit in prediction, people with autism manifest low perceptual construal and are impaired at traversing psychological distances, and Gilead et al.'s hierarchy from iconic to multimodal to fully abstract, socially communicated representations is exactly the hierarchy of representational impairment in autism, making autism a natural behavioural and neurophysiological test case for the prediction-abstraction relationship.}, } @article {pmid32645792, year = {2020}, author = {Davis, CP and Altmann, GTM and Yee, E}, title = {Language as a mental travel guide.}, journal = {The Behavioral and brain sciences}, volume = {43}, number = {}, pages = {e125}, doi = {10.1017/S0140525X19003182}, pmid = {32645792}, issn = {1469-1825}, mesh = {Brain ; Cognition ; *Cognitive Science ; Humans ; *Language ; }, abstract = {Gilead et al.'s approach to human cognition places abstraction and prediction at the heart of "mental travel" under a "representational diversity" perspective that embraces foundational concepts in cognitive science. But, it gives insufficient credit to the possibility that the process of abstraction produces a gradient, and underestimates the importance of a highly influential domain in predictive cognition: language, and related, the emergence of experientially based structure through time.}, } @article {pmid32638994, year = {2020}, author = {Yang, H and Zheng, L and Zhang, Y and Yang, M and Wei, S}, title = {Comments on 'Association of FcϵRIβ polymorphisms with risk of asthma and allergic rhinitis: evidence based on 29 case-control studies'.}, journal = {Bioscience reports}, volume = {40}, number = {7}, pages = {}, pmid = {32638994}, issn = {1573-4935}, mesh = {*Asthma/epidemiology/genetics ; Case-Control Studies ; Humans ; Polymorphism, Single Nucleotide ; Receptors, IgE/genetics ; *Rhinitis, Allergic/epidemiology/genetics ; }, abstract = {Guo et al. (Bioscience Reports (2018) 38, BSR20180177) published a meta-analysis concerning the association between five single nucleotide polymorphisms (SNPs) in the high-affinity IgE receptor β chain (FcεRIβ) gene, namely E237G, -109 C/T, RsaI_in2, RsaI_ex7, and I181L, and risk of asthma and allergic rhinitis based on available 29 case-control studies. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of association of SNPs in FcεRIβ gene with allergic diseases risk. They found that FcεRIβ E237G (237G vs. 237E: OR = 1.28, 95% CI = 1.06-1.53) and -109 C/T (TT vs. CT+CC: OR = 1.58, 95% CI = 1.26-1.98) were risk factors for allergic diseases. Guo et al.'s findings are interesting, but we found that several issues should be clarified after carefully reading the paper. Here, we intended to comment on these data clarifications.}, } @article {pmid32638691, year = {2020}, author = {Eaves, L}, title = {Birmingham and Beyond.}, journal = {Twin research and human genetics : the official journal of the International Society for Twin Studies}, volume = {23}, number = {2}, pages = {68-71}, doi = {10.1017/thg.2020.27}, pmid = {32638691}, issn = {1832-4274}, mesh = {Genetics, Behavioral/*history ; History, 20th Century ; History, 21st Century ; Human Genetics/*history ; Humans ; Models, Genetic ; Twin Studies as Topic/history ; Twins/*genetics ; }, abstract = {Nick Martin was a doctoral student of mine at the University of Birmingham in the mid 1970s. In this review, I discuss two of Nick's earliest and most seminal contributions to the field of behavior genetics. First, Martin and Eaves' (1977) extension of the model-fitting approach to multivariate data, which laid the theoretical groundwork for a generation of multivariate behavior genetic studies. Second, the Martin et al.'s (1978) manuscript on the power of the classical twin design, which showed that thousands of twin pairs would be required in order to reliably estimate components of variance, and has served as impetus for the formation of large-scale twin registries across the world. I discuss these contributions against the historical backdrop of a time when we and others were struggling with the challenge of figuring out how to incorporate gene-by-environment interaction, gene-environment correlation, mate selection and cultural transmission into more complex genetic models of human behavior.}, } @article {pmid32638498, year = {2020}, author = {Núñez, R and Allen, M and Gao, R and Miller Rigoli, C and Relaford-Doyle, J and Semenuks, A}, title = {For the Sciences They Are A-Changin': A Response to Commentaries on Núñez et al.'s (2019) "What Happened to Cognitive Science?".}, journal = {Topics in cognitive science}, volume = {12}, number = {3}, pages = {790-803}, doi = {10.1111/tops.12511}, pmid = {32638498}, issn = {1756-8765}, mesh = {*Cognitive Science ; Humans ; }, abstract = {A recent issue of Topics in Cognitive Science featured 11 thoughtful commentaries responding to our article "What happened to cognitive science?" (Núñez et al., 2019). Here, we identify several themes that arose in those commentaries and respond to each. Crucial to understanding our original article is the fundamental distinction between multidisciplinary and interdisciplinary endeavors: Cognitive science began (and has stayed) as multidisciplinary but has failed to move on to form a cohesive interdisciplinary field. We clarify and elaborate our original argument and reiterate the importance of a data-driven evaluation of the current status of the field, which exhibits a marked disciplinary imbalance, a lack of a coherent conceptual core, and a striking absence of a consistent curriculum in the institutions that grant degrees in this domain. Half a century after the creation of cognitive science, it may now be a good time to revisit goals and visions for how to best approach the ever-fascinating scientific study of the mind(s).}, } @article {pmid32621521, year = {2020}, author = {Attia, E}, title = {Don't shortchange a long illness: A commentary on Severe and Enduring Anorexia Nervosa.}, journal = {The International journal of eating disorders}, volume = {53}, number = {8}, pages = {1324-1325}, doi = {10.1002/eat.23328}, pmid = {32621521}, issn = {1098-108X}, mesh = {Adult ; *Anorexia Nervosa ; Humans ; }, abstract = {Wonderlich et al.'s manuscript "Severe and Enduring Anorexia Nervosa: Update and Observations about the Current Clinical Reality" reviews Severe and Enduring Anorexia Nervosa (SE-AN) from several perspectives, hoping to stimulate discussion among clinicians, researchers, and other stakeholders about needed next steps for furthering the science relevant to the severe and enduring form of illness that affects a subgroup of individuals with AN. Among the important reasons for a new discussion of SE-AN is that health care has evolved in ways that have reduced comprehensive services for those who are more seriously affected. It is critical that adults with SE-AN be examined empirically to help identify effective strategies for clinical management and that health care policies assure parity for this seriously affected group.}, } @article {pmid32612220, year = {2020}, author = {Zhao, J and Tian, X and Zhu, Y and Zhang, Z and Rydkina, E and Yuan, Y and Zhang, H and Roy, B and Cornwell, A and Nevo, E and Shang, X and Huang, R and Kristiansen, K and Seluanov, A and Fang, X and Gorbunova, V}, title = {Reply to: Transformation of naked mole-rat cells.}, journal = {Nature}, volume = {583}, number = {7814}, pages = {E8-E13}, pmid = {32612220}, issn = {1476-4687}, support = {P01 AG047200/AG/NIA NIH HHS/United States ; R01 AG027237/AG/NIA NIH HHS/United States ; R01 AG031227/AG/NIA NIH HHS/United States ; R03 AG052365/AG/NIA NIH HHS/United States ; }, mesh = {Animals ; *Fibroblasts ; *Mole Rats ; }, abstract = {It has been independently demonstrated by us and Liang et al. that naked mole-rat (NMR) cells are more resistant to SV40LT and H-RasV12-induced transformation than mouse cells. In the accompanying comment, Hadi et al. argued that NMR cells and mouse cells are equally susceptible to oncogenic transformation by SV40LT and H-RasV12. However, their observations are based on much higher expression levels of H-RasV12 than in our study and Liang et al.’s study. Our new RNA-seq data shows that NMR cells are strikingly more resistant to transcriptomic changes induced by oncogenic Ras than mouse, blind mole-rat, and human cells, revealing suppressed Ras signaling as an anti-cancer mechanism in NMR cells. Furthermore, we found that high expression of H-RasV12 abolished this mechanism and rendered NMR cells susceptible to oncogenic transformation. Our results explain that the ostensibly equal susceptibility of NMR and mouse cells to transformation observed by Hadi et al. was resulted from high levels of H-RasV12 overriding anti-cancer mechanisms of the naked mole rat.}, } @article {pmid32610674, year = {2020}, author = {Jaakkola, K and Bruck, JN and Connor, RC and Montgomery, SH and King, SL}, title = {Bias and Misrepresentation of Science Undermines Productive Discourse on Animal Welfare Policy: A Case Study.}, journal = {Animals : an open access journal from MDPI}, volume = {10}, number = {7}, pages = {}, pmid = {32610674}, issn = {2076-2615}, abstract = {Reliable scientific knowledge is crucial for informing legislative, regulatory, and policy decisions in a variety of areas. To that end, scientific reviews of topical issues can be invaluable tools for informing productive discourse and decision-making, assuming these reviews represent the target body of scientific knowledge as completely, accurately, and objectively as possible. Unfortunately, not all reviews live up to this standard. As a case in point, Marino et al.'s [1] review regarding the welfare of killer whales in captivity contains methodological flaws and misrepresentations of the scientific literature, including problematic referencing, overinterpretation of the data, misleading word choice, and biased argumentation. These errors and misrepresentations undermine the authors' conclusions and make it impossible to determine the true state of knowledge of the relevant issues. To achieve the goal of properly informing public discourse and policy on this and other issues, it is imperative that scientists and science communicators strive for higher standards of analysis, argumentation, and objectivity, in order to clearly communicate what is known, what is not known, what conclusions are supported by the data, and where we are lacking the data necessary to draw reliable conclusions.}, } @article {pmid32608326, year = {2021}, author = {Kwasnicka, D and Ntoumanis, N and Sniehotta, FF}, title = {Setting performance and learning goals is useful for active and inactive individuals, if goals are personalized and flexible: commentary on Swann et al. (2020).}, journal = {Health psychology review}, volume = {15}, number = {1}, pages = {51-55}, doi = {10.1080/17437199.2020.1762107}, pmid = {32608326}, issn = {1743-7202}, mesh = {Exercise ; *Goals ; Humans ; Learning ; *Motivation ; Sedentary Behavior ; }, abstract = {This commentary expands on the recent critical review by Swann et al. (2020) which aimed to update the applications of Goal-Setting Theory (Locke & Latham, 2019) in physical activity promotion. Drawing from other work on goal striving and behaviour change, we make four key points to further elaborate on Swann et al.'s review. First, goals are more likely to be enacted if they are specific, personally relevant and pursued for autonomous motives; performance goals can be useful for inactive individuals if set appropriately and self-endorsed. Second, goal striving needs to be flexible and adjustable, and to consider goal priorities and time factors relevant to goal engagement and disengagement. Goal-Setting Theory would therefore benefit from being expanded to add the factors of goal priority, context, and time. Third, research on goal setting in physical activity could benefit from embracing idiographic designs and interventions. Fourth, other theoretical approaches to goal striving should be considered when discussing goal setting in physical activity promotion.}, } @article {pmid32594886, year = {2022}, author = {Duff, K and Hammers, DB}, title = {Practice effects in mild cognitive impairment: A validation of Calamia et al. (2012).}, journal = {The Clinical neuropsychologist}, volume = {36}, number = {3}, pages = {571-583}, pmid = {32594886}, issn = {1744-4144}, support = {R01 AG045163/AG/NIA NIH HHS/United States ; R01 AG055428/AG/NIA NIH HHS/United States ; }, mesh = {Aged ; *Cognitive Dysfunction/diagnosis/psychology ; Humans ; Neuropsychological Tests ; }, abstract = {OBJECTIVE: In a meta-analysis examining practice effects on repeated neuropsychological testing, Calamia et al. (2012) provided information to predict practice effects in healthy and clinical samples across a range of cognitive domains. However, these estimates have not been validated.

METHOD: This study used these prediction estimate calculations to predict follow-up scores across one year on a brief battery of neuropsychological tests in a sample of 93 older adults with amnestic mild cognitive impairment. The predicted follow-up scores were compared to observed follow-up scores.

RESULTS: Using Calamia et al. model's intercept, age, retest interval, clinical status, and specific cognitive tests, three of the seven observed follow-up scores in this cognitive battery were significantly lower than the Calamia et al. predicted follow-up scores. Differences between individual participants' observed and predicted follow-up scores were more striking. For example, on Delayed Recall of the Hopkins Verbal Learning Test - Revised, 40% of the sample had Calamia et al. predicted scores that were one or more standard deviations above their observed scores. These differences were most notable on tests that were not in Calamia et al.'s cognitive battery, suggesting the meta-analysis results may not generalize as well to other tests.

CONCLUSIONS: Although Calamia et al. provided a method for predicting practice effects and follow-up scores, these results raise caution when using them in MCI, especially on cognitive tests that were not in their meta-analysis.}, } @article {pmid32586208, year = {2020}, author = {Gervais, WM and McKee, SE and Malik, S}, title = {Do Religious Primes Increase Risk Taking? Evidence Against "Anticipating Divine Protection" in Two Preregistered Direct Replications of Kupor, Laurin, and Levav (2015).}, journal = {Psychological science}, volume = {31}, number = {7}, pages = {858-864}, doi = {10.1177/0956797620922477}, pmid = {32586208}, issn = {1467-9280}, mesh = {Adult ; Bayes Theorem ; *Dangerous Behavior ; Female ; Humans ; Male ; Meta-Analysis as Topic ; Middle Aged ; Morals ; *Religion and Psychology ; *Risk-Taking ; Young Adult ; }, abstract = {Do reminders of God encourage people to take more risks? Kupor, Laurin, and Levav (2015) reported nine studies that all yielded statistically significant results consistent with the hypothesis that they do. We conducted two large-sample Preregistered Direct Replications (N = 1,104) of studies in Kupor et al.'s article (Studies 1a and 1b) and evaluated replicability via (a) statistical significance, (b) a "small-telescopes" approach, (c) Bayes factors (BFs), and (d) meta-analyses pooled across original and replication studies. None of these approaches replicated the original studies' effects. Combining both original studies and both replications yielded strong evidence in support of the null over a default alternative hypothesis, BF01 = 11.04, meaning that the totality of evidence speaks against the possibility that religious primes increased nonmoral risk taking in these designs. This suggests that support for the "anticipating-divine-protection" hypothesis may be overstated.}, } @article {pmid32581925, year = {2020}, author = {Savahl, S}, title = {Children's Hope in South Africa: A Population-Based Study.}, journal = {Frontiers in psychology}, volume = {11}, number = {}, pages = {1023}, pmid = {32581925}, issn = {1664-1078}, abstract = {A growing body of research has provided evidence for the cognitive motivational construct of hope as a psychological strength, particularly for children in adverse social circumstances. In children, hope is defined as a set of cognitions focused on children's agency to contemplate workable goals, to identify pathways to achieve those goals and the intrinsic beliefs about their capacity to activate sustained movement toward those goals. Using data from the third wave of the Children's Worlds International Survey on Children's Well-Being, the study aimed to explore children's hope amongst a random population-based sample of children in South Africa. The study further aimed to explore children's level of hope across the nine provincial regions of South Africa. Data were collected using Snyder et al.'s (1997) Children's Hope Scale (CHS). Confirmatory factor analysis (CFA) was used to analyze the data, with multi-group CFA used to analyze the data across provincial regions. The study found an appropriate fit structure for the CHS using the overall pooled sample. The mean score on the CHS for the national sample was of 4.781 (SD = 1.082). Measurement invariance demonstrated the tenability of scalar invariance, which indicates comparability across correlations, regressions and mean scores. Mean scores ranged from 4.511 (SD = 1.163) for the Northern Cape to 4.982. (SD = 0.974) for the Western Cape. Five provinces (Eastern Cape, Northern Cape, Free State, Mpumalanga, and KwaZulu Natal) scored below the national mean, while four provinces (North West, Western Cape, Limpopo, and Gauteng) scored above.}, } @article {pmid32578889, year = {2021}, author = {Falligant, JM and Kranak, MP and McNulty, MK and Schmidt, JD and Hausman, NL and Rooker, GW}, title = {Prevalence of renewal of problem behavior: Replication and extension to an inpatient setting.}, journal = {Journal of applied behavior analysis}, volume = {54}, number = {1}, pages = {367-373}, pmid = {32578889}, issn = {1938-3703}, support = {P50 HD103538/HD/NICHD NIH HHS/United States ; }, mesh = {Conditioning, Operant ; Extinction, Psychological ; Humans ; Inpatients ; Prevalence ; *Problem Behavior ; Reinforcement, Psychology ; }, abstract = {Individuals with intellectual and developmental disabilities who exhibit problem behavior often receive behavioral assessment and treatment in specialized inpatient and outpatient clinics. However, problem behavior sometimes reemerges as a function of changes in contexts and stimulus conditions, such as returning to the home environment. This reemergence is called renewal. Recently, Muething et al. (2020) found that renewal occurred in over half (67%) of cases from an outpatient clinic. Their sample was obtained exclusively from an outpatient setting and despite the applied relevance of renewal, its clinical prevalence in other populations is unknown. Accordingly, we replicated Muething et al.'s procedures and analyzed renewal in 37 inpatient treatment applications across 34 cases via consecutive-controlled case series. Renewal was present in 59% of cases; however, we found that renewal occurred in only 24% of context changes compared to 42% reported by Muething et al. Various factors related to the prevalence of renewal were evaluated.}, } @article {pmid32572856, year = {2021}, author = {Mascolo, MF}, title = {Inching Toward a Unified Metatheory for Psychology.}, journal = {Integrative psychological & behavioral science}, volume = {55}, number = {1}, pages = {198-211}, pmid = {32572856}, issn = {1936-3567}, mesh = {*Biological Evolution ; Clay ; Humans ; }, abstract = {Zagaria et al. (2020) have aptly suggested that as a discipline, psychology is a giant with feet of clay. Drawing on the content of introductory textbooks, the authors show that there is little coherence and consensus about the meaning of key psychological terms - including such terms as psychology, mind, behavior. Drawing on evidence marking psychology is a "soft" science, the authors suggest that psychology can profit by adopting the "hard" foundation of evolutionary psychology as its metatheory. While Zagaria et al.'s characterization of psychology's fractious foundation has deep merit, their desire to erect a psychological metatheory on evolutionary psychology is unlikely to solve the problem they so aptly identify. At the least, I suggest a unified metatheory must: (a) establish a shared psychological lexicon; (b) elaborate a methodology that coordinates first-, second- and third-person modes of inquiry, and (c) develop a process model that describes psychological functioning at the biological, psychological and socio-cultural levels of analysis. To illustrate, I describe how contemporary relational and systems frameworks provide a framework that can move us in these directions.}, } @article {pmid32571498, year = {2020}, author = {Frew, JW and Piguet, V}, title = {Ex Vivo Models and Interpretation of Mechanistic Studies in Hidradenitis Suppurativa.}, journal = {The Journal of investigative dermatology}, volume = {140}, number = {7}, pages = {1323-1326}, doi = {10.1016/j.jid.2020.02.014}, pmid = {32571498}, issn = {1523-1747}, mesh = {Animals ; *Hidradenitis Suppurativa ; Humans ; Interleukin-1 ; Skin ; }, abstract = {Current ex vivo and animal models of hidradenitis suppurativa (HS) display issues with fidelity and validity to human disease. Vossen et al.'s Transwell culture system holds potential to reliably assess mechanistic pathways in HS. Consideration of the sites of control tissue and comparison of the Transwell model against skin explant models would increase the validity of this method of inquiry.}, } @article {pmid32568199, year = {2020}, author = {Robillard, JM and Goldman, IP and Prescott, TJ and Michaud, F}, title = {Addressing the Ethics of Telepresence Applications Through End-User Engagement.}, journal = {Journal of Alzheimer's disease : JAD}, volume = {76}, number = {2}, pages = {457-460}, doi = {10.3233/JAD-200154}, pmid = {32568199}, issn = {1875-8908}, mesh = {Aged ; *Cognitive Dysfunction ; Friends ; Humans ; Intelligence ; *Robotics ; }, abstract = {Portacolone et al.'s Ethics Review highlights the ethical challenges associated with the implementation of telepresence devices and applications in the context of aging and dementia. In this response, we review ethical considerations as they relate to specific modalities of telepresence, with an emphasis on the continuum of potential interaction agents, from known individuals to fully automated and intelligent interlocutors. We further discuss areas in need of empirical evidence to inform regulatory efforts in telepresence. We close with a call for meaningful end-user engagement at all stages of technology development.}, } @article {pmid32554080, year = {2020}, author = {Yoon, KH and Park, SY and Park, JY and Kim, EJ and Kim, SJ and Kwon, YB and Kim, SG}, title = {Influence of Posterior Tibial Slope on Clinical Outcomes and Survivorship After Anterior Cruciate Ligament Reconstruction Using Hamstring Autografts: A Minimum of 10-Year Follow-Up.}, journal = {Arthroscopy : the journal of arthroscopic & related surgery : official publication of the Arthroscopy Association of North America and the International Arthroscopy Association}, volume = {36}, number = {10}, pages = {2718-2727}, doi = {10.1016/j.arthro.2020.06.011}, pmid = {32554080}, issn = {1526-3231}, mesh = {Adolescent ; Adult ; Anterior Cruciate Ligament Injuries/*surgery ; *Anterior Cruciate Ligament Reconstruction ; *Autografts ; Female ; Follow-Up Studies ; Hamstring Muscles/*surgery ; Humans ; Kaplan-Meier Estimate ; Knee Joint/surgery ; Lysholm Knee Score ; Magnetic Resonance Imaging ; Male ; Meniscectomy ; Middle Aged ; Preoperative Period ; Radiography ; Retrospective Studies ; Transplantation, Autologous ; Treatment Failure ; Young Adult ; }, abstract = {PURPOSE: To investigate the influence of medial and lateral posterior tibial slope (PTS) on long-term clinical outcomes and survivorship after anterior cruciate ligament (ACL) reconstruction using hamstring autografts.

METHODS: A total of 232 patients (mean age, 28.2 ± 8.9 years) who underwent primary ACL reconstruction from October 2002 to July 2007 were retrospectively reviewed. Patients with multiple ligament reconstruction, total meniscectomy, contralateral knee surgery before ACL reconstruction, open growth plate, and less than 10-year follow-up were excluded in the study. The medial and lateral PTS were measured from preoperative magnetic resonance imaging. Based on Li et al.'s previous study, the patients were divided into 2 groups according to their medial PTS (≤5.6° vs >5.6°) and lateral PTS (≤3.8° vs >3.8°), respectively. Clinical outcomes (clinical scores, stability tests and failure rate) were compared between the groups at the last follow-up. Furthermore, survival analysis was performed using the Kaplan-Meier method.

RESULTS: All clinical scores (International Knee Documentation Committee subjective, Lysholm, and Tegner activity scores) and stability tests (physical examinations and side-to-side difference in Telos stress radiographs) were insignificantly different between the 2 groups classified based on medial or lateral PTS. However, the failure rate was significantly higher in patients with medial PTS >5.6° (16.1% vs 5.1%, P = .01) or lateral PTS >3.8° (14.5% vs 4.7%; P = .01). The odds ratios of graft failure due to increased medial and lateral PTS were 3.18 (95% confidence interval, 1.22-8.28; P = .02) and 3.43 (95% confidence interval, 1.29-9.09; P = .01), respectively. In addition, the 10-year survivorship was significantly lower in patients with medial PTS >5.6° (83.9% vs 94.9%, P = .01) or lateral PTS >3.8° (85.5% vs 96.0%; P = .01).

CONCLUSIONS: Increased medial (>5.6°) and lateral (>3.8°) PTS were associated with higher failure rate and lower survivorship at a minimum of 10-year follow-up after primary ACL reconstruction using hamstring autografts.

LEVEL OF EVIDENCE: Level III, retrospective comparative trial.}, } @article {pmid32547681, year = {2020}, author = {Wang, J and Hu, WW and Jiang, Z and Feng, MJ}, title = {Advances in treatment of neurodegenerative diseases: Perspectives for combination of stem cells with neurotrophic factors.}, journal = {World journal of stem cells}, volume = {12}, number = {5}, pages = {323-338}, pmid = {32547681}, issn = {1948-0210}, abstract = {Neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, Huntington's disease and amyotrophic lateral sclerosis, are a group of incurable neurological disorders, characterized by the chronic progressive loss of different neuronal subtypes. However, despite its increasing prevalence among the ever-increasing aging population, little progress has been made in the coincident immense efforts towards development of therapeutic agents. Research interest has recently turned towards stem cells including stem cells-derived exosomes, neurotrophic factors, and their combination as potential therapeutic agents in neurodegenerative diseases. In this review, we summarize the progress in therapeutic strategies based on stem cells combined with neurotrophic factors and mesenchymal stem cells-derived exosomes for neurodegenerative diseases, with an emphasis on the combination therapy.}, } @article {pmid32542060, year = {2020}, author = {Fernandes, S and Aharoni, E and Harenski, CL and Caldwell, M and Kiehl, KA}, title = {Anomalous Moral Intuitions in Juvenile Offenders with Psychopathic Traits.}, journal = {Journal of research in personality}, volume = {86}, number = {}, pages = {}, pmid = {32542060}, issn = {0092-6566}, support = {R01 HD082257/HD/NICHD NIH HHS/United States ; R01 HD092331/HD/NICHD NIH HHS/United States ; R01 MH071896/MH/NIMH NIH HHS/United States ; }, abstract = {Since the historical conception of psychopathy, researchers have been interested in understanding moral functioning among psychopathic individuals. The present study investigated the association between psychopathic traits and moral intuitions among incarcerated juvenile offenders (N = 178). Participants were assessed using the Psychopathy Checklist:Youth Version (Forth et al., 2003) and the Moral Foundations Questionnaire (Graham et al., 2011), which defines five core moral foundations: Harm/care, Fairness/reciprocity, Ingroup/loyalty, Authority/respect, and Purity/sanctity. As expected, psychopathy in juvenile offenders negatively predicted endorsement of all five foundations. This study is the first to demonstrate broad abnormalities in Haidt et al.'s moral foundations in a juvenile sample and can help explain delinquent behavior in juveniles with psychopathic traits. Implications for theories of psychopathy are discussed.}, } @article {pmid32539618, year = {2020}, author = {Will, P and Rothwell, A and Chisholm, JD and Risko, EF and Kingstone, A}, title = {Cognitive load but not immersion plays a significant role in embodied cognition as seen through the spontaneous act of leaning.}, journal = {Quarterly journal of experimental psychology (2006)}, volume = {73}, number = {11}, pages = {2000-2007}, doi = {10.1177/1747021820939088}, pmid = {32539618}, issn = {1747-0226}, mesh = {Brain ; *Cognition ; *Environment ; Female ; Gestures ; Humans ; Male ; Models, Psychological ; *Posture ; Young Adult ; }, abstract = {An important aspect of embodied approaches to cognition is the idea that human cognition does not occur simply in the brain, but is influenced by a complex bi-directional interplay between the brain, body, and external environment. Though embodied cognition is often studied in a controlled laboratory setting, by its very nature it can arise spontaneously in everyday life (e.g., gesturing). A recent paper by Chisholm et al. suggested that leaning while playing a video game may be another instance of a natural spontaneous expression of embodied cognition that can be studied to gain insight into a person's ongoing covert cognition. Consistent with this proposal, Chisholm et al. found that, like gestures, leaning increases when cognitive demand is increased. However, in Chisholm et al., immersion also increased with cognitive demand. We argue that their test to exclude it as a contributing factor-by holding cognitive demand constant while manipulating immersion-was limited. Despite their test, it remains possible and plausible that cognitive demand has an effect on leaning only when immersion increases. To address this issue, the present study systematically varied demand and immersion. We replicate Chisholm et al.'s finding that leaning increases with cognitive load. We also show that the effect of load is not influenced by a robust and reliable change in immersion. Collectively our results provide new and converging evidence that spontaneous overt embodiment of an individual's intention is modulated by cognitive demand, and emphasises the utility of using natural behaviours to understand the embodiment of cognition.}, } @article {pmid32538711, year = {2021}, author = {Danioni, F and Barni, D}, title = {Value priorities, impression management and self-deceptive enhancement: Once again, much substance and a little bit of style.}, journal = {The Journal of social psychology}, volume = {161}, number = {2}, pages = {146-159}, doi = {10.1080/00224545.2020.1778619}, pmid = {32538711}, issn = {1940-1183}, mesh = {Adolescent ; Adult ; *Attitude ; Female ; Humans ; Italy ; Male ; Self Report ; *Social Desirability ; Surveys and Questionnaires ; Young Adult ; }, abstract = {The connection between self-reported personal values and socially desirable responding in social psychology has been backed up by little empirical evidence. This study expands upon the pioneering work carried out by Schwartz and colleagues by analyzing the relationship between values and social desirability through the use of different self-report measures of values and by considering the multidimensional nature of social desirability. The study involved 224 Italian respondents (63.4% female, mean age = 22.39, SD = 2.47) who completed a questionnaire. Results confirmed Schwartz et al.'s previous findings supporting the substantive hypothesis. Specifically, impression management was more related to values highlighting the importance of social harmony (i.e., conservation and self-transcendence) rather than to those characterized by a personal focus (i.e., openness to change and self-enhancement). However, a different pattern of connection was found for self-deceptive enhancement. This study addresses how to deal with social desirability in research into personal values.}, } @article {pmid32532233, year = {2020}, author = {Minian, N and Corrin, T and Lingam, M and deRuiter, WK and Rodak, T and Taylor, VH and Manson, H and Dragonetti, R and Zawertailo, L and Melamed, OC and Hahn, M and Selby, P}, title = {Identifying contexts and mechanisms in multiple behavior change interventions affecting smoking cessation success: a rapid realist review.}, journal = {BMC public health}, volume = {20}, number = {1}, pages = {918}, pmid = {32532233}, issn = {1471-2458}, support = {1617-HQ-000045//Public Health Agency of Canada/ ; }, mesh = {Behavior Therapy/*methods ; *Health Behavior ; Humans ; Smoking/*psychology ; Smoking Cessation/*methods ; Treatment Outcome ; }, abstract = {BACKGROUND: Smoking continues to be a leading cause of preventable chronic disease-related morbidity and mortality, excess healthcare expenditure, and lost work productivity. Tobacco users are disproportionately more likely to be engaging in other modifiable risk behaviours such as excess alcohol consumption, physical inactivity, and poor diet. While hundreds of interventions addressing the clustering of smoking and other modifiable risk behaviours have been conducted worldwide, there is insufficient information available about the context and mechanisms in these interventions that promote successful smoking cessation. The aim of this rapid realist review was to identify possible contexts and mechanisms used in multiple health behaviour change interventions (targeting tobacco and two or more additional risk behaviours) that are associated with improving smoking cessation outcome.

METHODS: This realist review method incorporated the following steps: (1) clarifying the scope, (2) searching for relevant evidence, (3) relevance confirmation, data extraction, and quality assessment, (4) data analysis and synthesis.

RESULTS: Of the 20,423 articles screened, 138 articles were included in this realist review. Following Michie et al.'s behavior change model (the COM-B model), capability, opportunity, and motivation were used to identify the mechanisms of behaviour change. Universally, increasing opportunities (i.e. factors that lie outside the individual that prompt the behaviour or make it possible) for participants to engage in healthy behaviours was associated with smoking cessation success. However, increasing participant's capability or motivation to make a behaviour change was only successful within certain contexts.

CONCLUSION: In order to address multiple health behaviours and assist individuals in quitting smoking, public health promotion interventions need to shift away from 'individualistic epidemiology' and invest resources into modifying factors that are external from the individual (i.e. creating a supportive environment).

TRIAL REGISTRATION: PROSPERO registration number: CRD42017064430.}, } @article {pmid32527393, year = {2020}, author = {Tujague, J}, title = {IARD Responds to Lim et al.'s (2019) Analysis of Framing and Completeness of Information Disseminated by Alcohol Industry-Funded Organizations.}, journal = {Journal of studies on alcohol and drugs}, volume = {81}, number = {3}, pages = {390-391}, pmid = {32527393}, issn = {1938-4114}, mesh = {*Alcohol Drinking ; *Breast Feeding ; Female ; Fertility ; Food Industry ; Humans ; Pregnancy ; Research Design ; }, } @article {pmid32527392, year = {2020}, author = {Sim, F and Chick, J and Neidle, S and Ogden, GR and Jarvis, S and Lidington, I and Leslien, H}, title = {A Rebuttal to Lim et al.'s (2019) Examination of Drinkaware's Presentation of Pregnancy, Fertility, Breastfeeding, and Alcohol Consumption Information.}, journal = {Journal of studies on alcohol and drugs}, volume = {81}, number = {3}, pages = {388-389}, pmid = {32527392}, issn = {1938-4114}, mesh = {*Alcohol Drinking ; *Breast Feeding ; Female ; Fertility ; Humans ; Pregnancy ; Research Design ; }, } @article {pmid32520968, year = {2020}, author = {Fält, E and Salari, R and Fabian, H and Sarkadi, A}, title = {Facilitating implementation of an evidence-based method to assess the mental health of 3-5-year-old children at Child Health Clinics: A mixed-methods process evaluation.}, journal = {PloS one}, volume = {15}, number = {6}, pages = {e0234383}, pmid = {32520968}, issn = {1932-6203}, mesh = {Child Health/*classification ; Child, Preschool ; Female ; Humans ; Male ; Mass Screening/methods ; Mental Health/*classification ; Parents ; Process Assessment, Health Care/*methods ; Psychometrics/methods ; School Teachers ; Surveys and Questionnaires ; Sweden/epidemiology ; }, abstract = {BACKGROUND: A number of instruments for identifying mental health problems in children are available, but there is limited knowledge about how to successfully implement their use in routine practice. The Strengths and Difficulties Questionnaire (SDQ) is an instrument with sound psychometric properties. Because using multi-informant SDQs when assessing young children has been emphasized, parent- and preschool teacher reports on the SDQ were introduced at Child Health Clinics in a Swedish municipality. This paper aimed to describe a facilitation programme developed to support the introduction of SDQ in clinical practice and evaluate how nurses perceived the facilitation strategies used. Moreover, the dose (delivery) and reach (response rate and population coverage) of the questionnaires were assessed.

METHODS: The mixed-methods process evaluation was guided by Moore et al.'s framework. Process data were excerpted from monitoring data, the trial database, research group documents, study materials, group interviews with nurses, and a survey on nurses' opinions and experiences of the screening method and the implementation process. Data were analysed using descriptive statistics and qualitative content analysis.

RESULTS: Facilitation strategies used included: educational meetings, educational outreach visits, newsletters, facilitative administrative support, and adaptations made in procedures and materials when required. Although nurses described a variety of barriers at the organisational and individual level, they were in favour of using the SDQ in clinical practice and emphasised the importance of the facilitation strategies used for its implementation. While dose levels (77-91%) indicated that nurses essentially delivered the intervention as intended, parental response rates remained between 54 and 63% and population coverage at around 50%, throughout the intervention period.

CONCLUSION: The facilitation program was perceived to support the implementation of the SDQ at the yearly check-ups in the child healthcare setting, but further efforts are required to reach all families.}, } @article {pmid32510759, year = {2020}, author = {Chen, Q and Yang, H and Rooks, B and Anthony, M and Zhang, Z and Tadin, D and Heffner, KL and Lin, FV}, title = {Autonomic flexibility reflects learning and associated neuroplasticity in old age.}, journal = {Human brain mapping}, volume = {41}, number = {13}, pages = {3608-3619}, pmid = {32510759}, issn = {1097-0193}, support = {R01 NR015452/NR/NINR NIH HHS/United States ; }, mesh = {Adaptation, Physiological/*physiology ; Aged ; Aged, 80 and over ; Aging/*physiology ; Autonomic Nervous System/*physiopathology ; Double-Blind Method ; Electrocardiography ; Female ; Humans ; Learning/*physiology ; Magnetic Resonance Imaging ; Male ; Neuronal Plasticity/*physiology ; Practice, Psychological ; }, abstract = {Effective learning in old age, particularly in those at risk for dementia, is essential for prolonging independent living. Individual variability in learning, however, is remarkable; that is, months of cognitive training to improve learning may be beneficial for some individuals but not others. So far, little is known about which neurophysiological mechanisms account for the observed variability in learning induced by cognitive training in older adults. By combining Lövdén et al.'s (2010, A theoretical framework for the study of adult cognitive plasticity. Psychological Bulletin, 136, 659-676) framework proposing the role of adaptation capacity in neuroplasticity and a neurovisceral integration model of the relationship between autonomic nervous system (ANS) and brain with a novel shapelet analytical approach that allows for accurate and interpretable analysis of time series data, we discovered an acute, ECG-derived ANS segment in response to cognitive training tasks at baseline that predicted learning outcomes from a 6-week cognitive training intervention. The relationship between the ANS segment and learning was robust in both cross-participant and cross-task analyses among a group of older adults with amnestic mild cognitive impairment. Furthermore, the revealed ANS shapelet significantly predicted training-induced neuroplasticity in the dorsal anterior cingulate cortex and select frontal regions during task fMRI. Across outcome measures, individuals were less likely to prospectively benefit from the cognitive training if their ECG data were more similar to this particular ANS segment at baseline. Our findings are among the first empirical evidence to confirm that adaptation capacity, indexed by ANS flexibility, predicts individual differences in learning and associated neuroplasticity beyond individual characteristics (e.g., age, education, neurodegeneration, total training).}, } @article {pmid32496632, year = {2020}, author = {Kielo, E and Suhonen, R and Ylönen, M and Viljamaa, J and Wahlroos, N and Stolt, M}, title = {A systematic and psychometric review of tests measuring nurses' wound care knowledge.}, journal = {International wound journal}, volume = {17}, number = {5}, pages = {1209-1224}, pmid = {32496632}, issn = {1742-481X}, mesh = {*Clinical Competence ; Humans ; *Pressure Ulcer/diagnosis ; Psychometrics ; Surveys and Questionnaires ; }, abstract = {Wound care is an important realm of nurses' clinical responsibilities, and a broad knowledge and range of skills are needed to perform efficient and safe patient care. Nurses' knowledge on this matter can be measured using knowledge tests. This study aims to identify, define, and analyse the knowledge tests developed for the measurement of nurses' wound care knowledge, and to evaluate the psychometric properties of the tests. This study was a systematic literature review. A total of 52 studies and 18 instruments were found. Of the 18 instruments, only 5 had been used more than once and were successful in a psychometric evaluation. These five instruments were analysed on the basis of their psychometric properties by using Zwakhalen et al.'s (2006) psychometric testing framework. According to the analysis, the Pressure Ulcer Knowledge Test (PUKT) and the Pressure Ulcer Knowledge Assessment Tool (PUKAT) were the most valid and reliable instruments for measuring nurses' wound care knowledge. Most of the instruments identified and analysed focused on pressure ulcers, indicating that future instruments could focus more on other types of wounds or on wound care in general in order to receive a broader understanding of nurses' wound care knowledge.}, } @article {pmid32483137, year = {2020}, author = {Pandey, DK and Pandey, A and Whattam, SA}, title = {Reply to 'Evidence for simple volcanic rifting not complex subduction initiation in the Laxmi Basin'.}, journal = {Nature communications}, volume = {11}, number = {1}, pages = {2734}, pmid = {32483137}, issn = {2041-1723}, abstract = {Recently, Pandey et al. proposed relict subduction initiation occurred along a passive margin in the northwest Indian Ocean, however, Clift et al. questioned their evidence for subduction initiation, suggesting that simpler rifting-related processes could more simply explain the available data. Here, Pandey et al. reply to Clift et al.’s comment, and argue that geochemical and isotope data for Laxmi basin lavas distinctly imply relict subduction initiation.}, } @article {pmid32481595, year = {2020}, author = {Xing, G and Liu, X and Hao, S and Li, X and Fan, L and Li, Y}, title = {Correction: Xing, G. et al.'s Diameter- and Length-Controlled Synthesis of Ultrathin ZnS Nanowires and Their Size-Dependent UV Absorption Properties, Photocatalytical Activities and Band-Edge Energy Levels. Nanomaterials 2019, 9, 220.}, journal = {Nanomaterials (Basel, Switzerland)}, volume = {10}, number = {6}, pages = {}, pmid = {32481595}, issn = {2079-4991}, abstract = {The authors wish to make the following corrections to this article [1][...].}, } @article {pmid32474830, year = {2021}, author = {Wallace, DM and Sweetman, A}, title = {Comorbid sleep apnea, post-traumatic stress disorder, and insomnia: underlying mechanisms and treatment implications-a commentary on El Solh et al.'s Impact of low arousal threshold on treatment of obstructive sleep apnea in patients with post-traumatic stress disorder.}, journal = {Sleep & breathing = Schlaf & Atmung}, volume = {25}, number = {2}, pages = {605-607}, pmid = {32474830}, issn = {1522-1709}, mesh = {Arousal ; Humans ; *Sleep Apnea Syndromes ; *Sleep Apnea, Obstructive/epidemiology/therapy ; *Sleep Initiation and Maintenance Disorders/epidemiology/therapy ; *Stress Disorders, Post-Traumatic/epidemiology/therapy ; }, } @article {pmid32469964, year = {2020}, author = {Schaming, TD and Sutherland, CS}, title = {Landscape- and local-scale habitat influences on occurrence and detection probability of Clark's nutcrackers: Implications for conservation.}, journal = {PloS one}, volume = {15}, number = {5}, pages = {e0233726}, pmid = {32469964}, issn = {1932-6203}, mesh = {Animals ; Conservation of Natural Resources ; Ecosystem ; Parks, Recreational ; *Passeriformes ; *Pinus ; Population Density ; Population Dynamics ; *Pseudotsuga ; Symbiosis ; United States ; }, abstract = {Whitebark pine (Pinus albicaulis), a keystone species and an obligate mutualist of the Clark's nutcracker (Nucifraga columbiana), is rapidly declining throughout its range. Evidence suggests this decline is leading to a downward trend in local nutcracker populations, which would in-turn decrease whitebark pine regeneration. Our objectives were to (1) evaluate temporal variation in nutcracker habitat use as a function of whitebark pine and Douglas-fir (Pseudotsuga menziesii) habitat, at local and landscape scales, (2) develop metrics for predicting when whitebark pine communities require intervention to sustain nutcracker visitation, and (3) test McKinney et al. (2009) and Barringer et al.'s (2012) models predicting nutcracker occurrence. Between 2009 and 2013, we carried out 3,135 audio-visual Clark's nutcracker surveys at 238 random points in the southern Greater Yellowstone Ecosystem. Using Bayesian occupancy models and cross-product model selection, we evaluated the association between nutcracker occurrence and habitat variables during five stages of the nutcracker annual cycle, while accounting for imperfect detection. Nutcracker occurrence was most strongly associated with the presence of cone-bearing whitebark pine trees (rather than cone density) and the area of whitebark pine on the landscape. To promote a high, >75%, probability of occurrence at a site within the study area, we recommend a management plan that achieves a landscape composed of a minimum of 12,500-25,000 ha of cone-bearing whitebark pine habitat within a 32.6 km radius. Additionally, an optimal habitat mosaic includes moderate levels of Douglas-fir habitat. Models currently used to guide whitebark pine management strategies underpredicted nutcracker occurrence in our study area, suggesting these strategies may not be appropriate in the region. We cannot predict how this mutualistic relationship will change as the population density of each species shifts. We therefore suggest conducting periodic surveys to re-evaluate the relationship as the environment changes and management strategies are implemented.}, } @article {pmid32460922, year = {2020}, author = {Gweon, H}, title = {The role of communication in acquisition, curation, and transmission of culture.}, journal = {The Behavioral and brain sciences}, volume = {43}, number = {}, pages = {e104}, doi = {10.1017/S0140525X19002863}, pmid = {32460922}, issn = {1469-1825}, mesh = {*Cognition ; *Communication ; Humans ; Knowledge ; Learning ; Social Behavior ; }, abstract = {Veissière et al.'s proposal aims to explain how cognition enables cultural learning, but fails to acknowledge a distinctively human behavior critical to this process: communication. Recent advances in developmental and computational cognitive science suggest that the social-cognitive capacities central to TTOM also support sophisticated yet remarkably early-emerging inferences and communicative behaviors that allow us to learn and share abstract knowledge.}, } @article {pmid32460909, year = {2020}, author = {Baggs, E and Chemero, A}, title = {Thinking with other minds.}, journal = {The Behavioral and brain sciences}, volume = {43}, number = {}, pages = {e92}, doi = {10.1017/S0140525X19002747}, pmid = {32460909}, issn = {1469-1825}, mesh = {Child ; *Cognition ; Humans ; *Learning ; }, abstract = {We applaud the ambition of Veissière et al.'s account of cultural learning, and the attempt to ground higher order thinking in embodied theory. However, the account is limited by loose terminology, and by its commitment to a view of the child learner as inference-maker. Vygotsky offers a more powerful view of cultural learning, one that is fully compatible with embodiment.}, } @article {pmid32458523, year = {2020}, author = {Utsumi, A}, title = {Exploring What Is Encoded in Distributional Word Vectors: A Neurobiologically Motivated Analysis.}, journal = {Cognitive science}, volume = {44}, number = {6}, pages = {e12844}, doi = {10.1111/cogs.12844}, pmid = {32458523}, issn = {1551-6709}, mesh = {Concept Formation ; Humans ; Knowledge ; *Semantics ; }, abstract = {The pervasive use of distributional semantic models or word embeddings for both cognitive modeling and practical application is because of their remarkable ability to represent the meanings of words. However, relatively little effort has been made to explore what types of information are encoded in distributional word vectors. Knowing the internal knowledge embedded in word vectors is important for cognitive modeling using distributional semantic models. Therefore, in this paper, we attempt to identify the knowledge encoded in word vectors by conducting a computational experiment using Binder et al.'s (2016) featural conceptual representations based on neurobiologically motivated attributes. In an experiment, these conceptual vectors are predicted from text-based word vectors using a neural network and linear transformation, and prediction performance is compared among various types of information. The analysis demonstrates that abstract information is generally predicted more accurately by word vectors than perceptual and spatiotemporal information, and specifically, the prediction accuracy of cognitive and social information is higher. Emotional information is also found to be successfully predicted for abstract words. These results indicate that language can be a major source of knowledge about abstract attributes, and they support the recent view that emphasizes the importance of language for abstract concepts. Furthermore, we show that word vectors can capture some types of perceptual and spatiotemporal information about concrete concepts and some relevant word categories. This suggests that language statistics can encode more perceptual knowledge than often expected.}, } @article {pmid32451090, year = {2020}, author = {Hoffmann, DL and Standish, CD and García-Diez, M and Pettitt, PB and Milton, JA and Zilhão, J and Alcolea-González, JJ and Cantalejo-Duarte, P and Collado, H and de Balbín, R and Lorblanchet, M and Ramos-Muñoz, J and Weniger, GC and Pike, AWG}, title = {Response to White et al.'s reply: 'Still no archaeological evidence that Neanderthals created Iberian cave art' [J. Hum. Evol. (2020) 102640].}, journal = {Journal of human evolution}, volume = {144}, number = {}, pages = {102810}, doi = {10.1016/j.jhevol.2020.102810}, pmid = {32451090}, issn = {1095-8606}, mesh = {Animals ; Archaeology ; Caves ; *Neanderthals ; }, } @article {pmid32444095, year = {2020}, author = {Stratil, JM}, title = {Evidence-based decision-making? On the limitations of Arshad et al.'s study used to justify political opinions on organ donation in Germany.}, journal = {Kidney international}, volume = {97}, number = {6}, pages = {1300}, doi = {10.1016/j.kint.2020.02.030}, pmid = {32444095}, issn = {1523-1755}, mesh = {Germany ; Humans ; *Organ Transplantation ; *Tissue and Organ Procurement ; }, } @article {pmid32429689, year = {2020}, author = {Lilford, RJ and Watson, SI}, title = {Comment on Hemming et al.'s 'Stepped-wedge trials should be classified as research for the purpose of ethical review'.}, journal = {Clinical trials (London, England)}, volume = {17}, number = {4}, pages = {459-460}, doi = {10.1177/1740774520920543}, pmid = {32429689}, issn = {1740-7753}, mesh = {*Ethical Review ; Sample Size ; }, } @article {pmid32411972, year = {2019}, author = {Wilson, A and Serafin, S and Seckiner, D and Berry, R and Mallett, X}, title = {Evaluating the utility of time-lapse imaging in the estimation of post-mortem interval: An Australian case study.}, journal = {Forensic science international. Synergy}, volume = {1}, number = {}, pages = {204-210}, pmid = {32411972}, issn = {2589-871X}, abstract = {Estimating post-mortem interval is an important aspect in forensic investigations. The aim of this study was to investigate if time-lapse imaging can be used to improve estimates of post-mortem interval using Megyesi et al.'s [1] method for a human donor decomposing in an Australian environment. To achieve this, time-lapse images were taken every 30 min over a 6-month period. The Megyesi et al. [1] total body score (TBS) system was used to quantify the level of decomposition of the donor for each image. Linear regression was performed to determine if observing decomposition more than once a day leads to increased accuracy in predicting PMI (post-mortem interval). Decomposition initially progressed quickly and then plateaued at 1004 hours PMI, with a TBS of 24. Individual timestamps were created from the time-lapse images taken each day at 08:00 hrs, 11:00 hrs, 14:00 hrs, 15:00 hrs, and 17:00 hrs. All timestamps produced R[2] values > 0.80, indicating that the Megyesi et al. [1] method accurately predicts PMI for this donor. The 08:00 hrs timestamp had the highest value R[2] = 0.886, whilst the combined timestamp (which included the scores from all five images for each 24-hour period) R[2] = 0.823 was the lowest. This study supports the validity of Megyesi et al.'s [1] TBS model to estimate PMI. Two other interesting findings were that the results suggest that scoring TBS multiple times per day does not improve estimates of PMI, however scoring TBS at daybreak produces more accurate results than scoring TBS later in the day. This may be an important consideration in forensic scenarios.}, } @article {pmid32402605, year = {2021}, author = {Woods, SW and Bearden, CE and Sabb, FW and Stone, WS and Torous, J and Cornblatt, BA and Perkins, DO and Cadenhead, KS and Addington, J and Powers, AR and Mathalon, DH and Calkins, ME and Wolf, DH and Corcoran, CM and Horton, LE and Mittal, VA and Schiffman, J and Ellman, LM and Strauss, GP and Mamah, D and Choi, J and Pearlson, GD and Shah, JL and Fusar-Poli, P and Arango, C and Perez, J and Koutsouleris, N and Wang, J and Kwon, JS and Walsh, BC and McGlashan, TH and Hyman, SE and Gur, RE and Cannon, TD and Kane, JM and Anticevic, A}, title = {Counterpoint. Early intervention for psychosis risk syndromes: Minimizing risk and maximizing benefit.}, journal = {Schizophrenia research}, volume = {227}, number = {}, pages = {10-17}, pmid = {32402605}, issn = {1573-2509}, support = {R01 MH111448/MH/NIMH NIH HHS/United States ; U01 MH081902/MH/NIMH NIH HHS/United States ; R01 MH105178/MH/NIMH NIH HHS/United States ; K23 MH115252/MH/NIMH NIH HHS/United States ; R01 MH105084/MH/NIMH NIH HHS/United States ; /WT_/Wellcome Trust/United Kingdom ; R01 MH116039/MH/NIMH NIH HHS/United States ; R01 MH113533/MH/NIMH NIH HHS/United States ; U01 MH081928/MH/NIMH NIH HHS/United States ; R01 MH112613/MH/NIMH NIH HHS/United States ; R33 MH111850/MH/NIMH NIH HHS/United States ; U01 MH082022/MH/NIMH NIH HHS/United States ; U01 MH081984/MH/NIMH NIH HHS/United States ; R01 MH115332/MH/NIMH NIH HHS/United States ; R01 MH112612/MH/NIMH NIH HHS/United States ; UL1 TR001863/TR/NCATS NIH HHS/United States ; R34 MH110506/MH/NIMH NIH HHS/United States ; R01 MH113565/MH/NIMH NIH HHS/United States ; R01 MH120088/MH/NIMH NIH HHS/United States ; R01 MH112189/MH/NIMH NIH HHS/United States ; U01 MH076989/MH/NIMH NIH HHS/United States ; R01 MH121095/MH/NIMH NIH HHS/United States ; R01 MH107558/MH/NIMH NIH HHS/United States ; R01 MH107250/MH/NIMH NIH HHS/United States ; K23 MH116130/MH/NIMH NIH HHS/United States ; R01 MH112545/MH/NIMH NIH HHS/United States ; R01 MH115000/MH/NIMH NIH HHS/United States ; R01 MH119219/MH/NIMH NIH HHS/United States ; R21 MH119438/MH/NIMH NIH HHS/United States ; U01 MH081857/MH/NIMH NIH HHS/United States ; U01 MH082004/MH/NIMH NIH HHS/United States ; R01 MH105243/MH/NIMH NIH HHS/United States ; U01 MH081944/MH/NIMH NIH HHS/United States ; }, mesh = {Humans ; *Psychotic Disorders/diagnosis/therapy ; Social Stigma ; Syndrome ; }, abstract = {BACKGROUND: Malhi et al. in this issue critique the clinical high risk (CHR) syndrome for psychosis.

METHOD: Response to points of critique.

RESULTS: We agree that inconsistency in CHR nomenclature should be minimized. We respectfully disagree on other points. In our view: a) individuals with CHR and their families need help, using existing interventions, even though we do not yet fully understand disease mechanisms; b) substantial progress has been made in identification of biomarkers; c) symptoms used to identify CHR are specific to psychotic illnesses; d) CHR diagnosis is not "extremely difficult"; e) the pattern of progression, although heterogenous, is discernible; f) "psychosis-like symptoms" are common but are not used to identify CHR; and g) on the point described as 'the real risk,' CHR diagnosis does not frequently cause harmful stigma.

DISCUSSION: Malhi et al.'s arguments do not fairly characterize progress in the CHR field nor efforts to minimize stigma. That said, much work remains in areas of consistent nomenclature, mechanisms of disease, dissecting heterogeneity, and biomarkers. With regard to what the authors term the "real risk" of stigma associated with a CHR "label," however, our view is that avoiding words like "risk" and "psychosis" reinforces the stigma that both they and we mean to oppose. Moreover, patients and their families benefit from being given a term that describes what is happening to them.}, } @article {pmid32396552, year = {2020}, author = {van der Pijl, MSG and Hollander, MH and van der Linden, T and Verweij, R and Holten, L and Kingma, E and de Jonge, A and Verhoeven, CJM}, title = {Left powerless: A qualitative social media content analysis of the Dutch #breakthesilence campaign on negative and traumatic experiences of labour and birth.}, journal = {PloS one}, volume = {15}, number = {5}, pages = {e0233114}, pmid = {32396552}, issn = {1932-6203}, mesh = {Adult ; Delivery, Obstetric ; Female ; Humans ; Labor, Obstetric ; *Maternal Health Services ; Netherlands ; Parturition ; Pregnancy ; *Social Media ; }, abstract = {INTRODUCTION: Disrespect and abuse during labour and birth are increasingly reported all over the world. In 2016, a Dutch client organization initiated an online campaign, #genoeggezwegen (#breakthesilence) which encouraged women to share negative and traumatic maternity care experiences. This study aimed (1) to determine what types of disrespect and abuse were described in #genoeggezwegen and (2) to gain a more detailed understanding of these experiences.

METHODS: A qualitative social media content analysis was carried out in two phases. (1) A deductive coding procedure was carried out to identify types of disrespect and abuse, using Bohren et al.'s existing typology of mistreatment during childbirth. (2) A separate, inductive coding procedure was performed to gain further understanding of the data.

RESULTS: 438 #genoeggezwegen stories were included. Based on the typology of mistreatment during childbirth, it was found that situations of ineffective communication, loss of autonomy and lack of informed consent and confidentiality were most often described. The inductive analysis revealed five major themes: ''lack of informed consent"; ''not being taken seriously and not being listened to"; ''lack of compassion"; ''use of force"; and ''short and long term consequences". "Left powerless" was identified as an overarching theme that occurred throughout all five main themes.

CONCLUSION: This study gives insight into the negative and traumatic maternity care experiences of Dutch women participating in the #genoeggezwegen campaign. This may indicate that disrespect and abuse during labour and birth do happen in the Netherlands, although the current study gives no insight into prevalence. The findings of this study may increase awareness amongst maternity care providers and the community of the existence of disrespect and abuse in Dutch maternity care, and encourage joint effort on improving care both individually and systemically/institutionally.}, } @article {pmid32393383, year = {2020}, author = {Funk, MF and Frisina-Deyo, AJ}, title = {Dry needling for spine related disorders: a scoping review.}, journal = {Chiropractic & manual therapies}, volume = {28}, number = {1}, pages = {23}, pmid = {32393383}, issn = {2045-709X}, mesh = {Dry Needling/*methods ; Humans ; Pain Measurement ; Pain Threshold ; Range of Motion, Articular ; Spinal Diseases/*therapy ; }, abstract = {INTRODUCTION/BACKGROUND: The depth and breadth of research on dry needling (DN) has not been evaluated specifically for symptomatic spine related disorders (SRD) from myofascial trigger points (TrP), disc, nerve and articular structures not due to serious pathologies. Current literature appears to support DN for treatment of TrP. Goals of this review include identifying research published on DN treatment for SRD, sites of treatment and outcomes studied.

METHODS: A scoping review was conducted following Levac et al.'s five part methodological framework to determine the current state of the literature regarding DN for patients with SRD.

RESULTS: Initial and secondary search strategies yielded 55 studies in the cervical (C) region (71.43%) and 22 in the thoracolumbar-pelvic (TLP) region (28.57%). Most were randomized controlled trials (60% in C, 45.45% in TLP) and clinical trials (18.18% in C, 22.78% in TLP). The most commonly treated condition was TrP for both the C and TLP regions. In the C region, DN was provided to 23 different muscles, with the trapezius as treatment site in 41.88% of studies. DN was applied to 31 different structures in the TLP region. In the C region, there was one treatment session in 23 studies (41.82%) and 2-6 treatments in 25 (45.45%%). For the TLP region, one DN treatment was provided in 8 of the 22 total studies (36.36%) and 2-6 in 9 (40.9%). The majority of experimental designs had DN as the sole intervention. For both C and TLP regions, visual analogue scale, pressure pain threshold and range of motion were the most common outcomes.

CONCLUSION: For SRD, DN was primarily applied to myofascial structures for pain or TrP diagnoses. Many outcomes were improved regardless of diagnosis or treatment parameters. Most studies applied just one treatment which may not reflect common clinical practice. Further research is warranted to determine optimal treatment duration and frequency. Most studies looked at DN as the sole intervention. It is unclear whether DN alone or in addition to other treatment procedures would provide superior outcomes. Functional outcome tools best suited to tracking the outcomes of DN for SRD should be explored.}, } @article {pmid32384090, year = {2020}, author = {Ng, YX and Koh, ZYK and Yap, HW and Tay, KT and Tan, XH and Ong, YT and Tan, LHE and Chin, AMC and Toh, YP and Shivananda, S and Compton, S and Mason, S and Kanesvaran, R and Krishna, L}, title = {Assessing mentoring: A scoping review of mentoring assessment tools in internal medicine between 1990 and 2019.}, journal = {PloS one}, volume = {15}, number = {5}, pages = {e0232511}, pmid = {32384090}, issn = {1932-6203}, mesh = {Educational Measurement/methods ; Humans ; Internal Medicine/*education ; *Mentoring ; *Mentors ; }, abstract = {BACKGROUND: Mentoring's success in enhancing a mentee's professional and personal development, and a host organisations' reputation has been called into question, amidst a lack of effective tools to evaluate mentoring relationships and guide oversight of mentoring programs. A scoping review is proposed to map available literature on mentoring assessment tools in Internal Medicine to guide design of new tools.

OBJECTIVE: The review aims to explore how novice mentoring is assessed in Internal Medicine, including the domains assessed, and the strengths and limitations of the assessment methods.

METHODS: Guided by Levac et al.'s framework for scoping reviews, 12 reviewers conducted independent literature reviews of assessment tools in novice mentoring in PubMed, Embase, Scopus, ERIC, Cochrane, GreyLit, Web of Science, Open Dissertations and British Education Index databases. A 'split approach' saw research members adopting either Braun and Clarke's approach to thematic analysis or directed content analysis to independently evaluate the data and improve validity and objectivity of the findings.

RESULTS: 9662 abstracts were identified, 187 full-text articles reviewed, and 54 full-text articles included. There was consensus on the themes and categories identified through the use of the split approach, which were the domains assessed and methods of assessment.

CONCLUSION: Most tools fail to contend with mentoring's evolving nature and provide mere snap shots of the mentoring process largely from the mentee's perspective. The lack of holistic, longitudinal and validated assessments propagate fears that ethical issues in mentoring are poorly recognized and addressed. To this end, we forward a framework for the design of 'fit for purpose' multi-dimensional tools.

PRACTICE POINTS: Most tools focus on the mentee's perspective, do not consider mentoring's evolving nature and fail to consider mentoring holistically nor longitudinallyA new tool capable of addressing these gaps must also consider inputs from all stakeholders and take a longitudinal perspective of mentoring.}, } @article {pmid32380998, year = {2020}, author = {Williams, O and Sarre, S and Papoulias, SC and Knowles, S and Robert, G and Beresford, P and Rose, D and Carr, S and Kaur, M and Palmer, VJ}, title = {Lost in the shadows: reflections on the dark side of co-production.}, journal = {Health research policy and systems}, volume = {18}, number = {1}, pages = {43}, pmid = {32380998}, issn = {1478-4505}, support = {KMRF-2016-05-017/DH_/Department of Health/United Kingdom ; }, mesh = {*Health Policy ; Humans ; *Motivation ; Research Personnel ; }, abstract = {This article is a response to Oliver et al.'s Commentary 'The dark side of coproduction: do the costs outweigh the benefits for health research?' recently published in Health Research Policy and Systems (2019, 17:33). The original commentary raises some important questions about how and when to co-produce health research, including highlighting various professional costs to those involved. However, we identify four related limitations in their inquiry, as follows: (1) the adoption of a problematically expansive definition of co-production that fails to acknowledge key features that distinguish co-production from broader collaboration; (2) a strong focus on technocratic rationales for co-producing research and a relative neglect of democratic rationales; (3) the transposition of legitimate concerns relating to collaboration between researchers and practitioners onto work with patients, service users and marginalised citizens; and (4) the presentation of bad practice as an inherent flaw, or indeed 'dark side', of co-production without attending to the corrupting influence of contextual factors within academic research that facilitate and even promote such malpractice. The Commentary's limitations can be seen to reflect the contemporary use of the term 'co-production' more broadly. We describe this phenomenon as 'cobiquity' - an apparent appetite for participatory research practice and increased emphasis on partnership working, in combination with the related emergence of a plethora of 'co' words, promoting a conflation of meanings and practices from different collaborative traditions. This phenomenon commonly leads to a misappropriation of the term 'co-production'. Our main motivation is to address this imprecision and the detrimental impact it has on efforts to enable co-production with marginalised and disadvantaged groups. We conclude that Oliver et al. stray too close to 'the problem' of 'co-production' seeing only the dark side rather than what is casting the shadows. We warn against such a restricted view and argue for greater scrutiny of the structural factors that largely explain academia's failure to accommodate and promote the egalitarian and utilitarian potential of co-produced research.}, } @article {pmid32371283, year = {2020}, author = {Jeong, Y and Harris, AP and Ali, O and Jung, Y}, title = {Bayes factor: A useful tool to quantitatively evaluate and compare performance of multiple stature estimation equations.}, journal = {Forensic science international}, volume = {312}, number = {}, pages = {110299}, doi = {10.1016/j.forsciint.2020.110299}, pmid = {32371283}, issn = {1872-6283}, abstract = {When stature estimation of incomplete skeletal remains is necessary, researchers select an estimation equation which will produce the most accurate estimates. The purpose of this study is to propose that, given prior information of a target sample, the Bayes factor can be a useful tool to quantitatively evaluate and compare performance of multiple equations in this regard. This study also explores the best-performing equations to reconstruct statures of Korean War casualties with a demonstration of equation comparisons by the Bayes factor. Thirty-three sets of stature estimates were generated using different equations based on the osteometric data of the Korean War casualties. The distribution of each set was compared to that of the population (i.e., Korean servicemen during the Korean War) using the Bayes factors and posterior probabilities generated by the R codes in the LearnBayes package. A higher Bayes factor indicates a closer similarity between the two distributions under comparison. The equation with the highest Bayes factor in this study was Choi et al.'s (1997) humerus equation (bf=9.84), followed by the femur equation of the same authors (bf=5.3). The Bayesian approach has advantages over the traditional frequentist approach primarily based on the p-value. Particularly, the Bayes factor can provide practical interpretations on the models under comparison, which allows for a quantitative prioritization of different models. Researchers can obtain more accurate stature estimates of a target sample by using the equation of the highest Bayes factor.}, } @article {pmid32368788, year = {2020}, author = {Zheng, LR and Atherton, OE and Trzesniewski, K and Robins, RW}, title = {Are self-esteem and academic achievement reciprocally related? Findings from a longitudinal study of Mexican-origin youth.}, journal = {Journal of personality}, volume = {88}, number = {6}, pages = {1058-1074}, doi = {10.1111/jopy.12550}, pmid = {32368788}, issn = {1467-6494}, support = {DA017902//National Institute on Drug Abuse, National Institute on Alcohol Abuse and Alcoholism/International ; }, mesh = {*Academic Success ; Adolescent ; Child ; Ethnicity ; Humans ; Longitudinal Studies ; Minority Groups ; Self Concept ; }, abstract = {OBJECTIVE: Previous research has shown that self-esteem is associated with academic achievement. However, few studies have used longitudinal data to examine how self-esteem and achievement co-develop over a long time span, and even fewer have focused on ethnic minority youth.

METHOD: We used data from a longitudinal study of Mexican-origin youth (N = 674) to examine the bidirectional associations between self-esteem and academic achievement from 5th to 11th grade. Global and domain-specific self-esteem (academic, honesty, peer relationships, appearance) were assessed at ages 10, 12, 14, and 16 using Marsh et al.'s (2005) Self-Description Questionnaire. Academic achievement was assessed at the same ages using self-reported grades and standardized test scores from school records.

RESULTS: Youth with high global and academic self-esteem showed relative improvements in their grades (but not test scores), and youth who received higher grades and test scores showed relative increases in global and academic self-esteem. Youth with high honesty self-esteem showed relative increases in grades and test scores, and youth with higher grades showed relative increases in peer relationship self-esteem.

CONCLUSION: Students who feel better about themselves tend to show improvements in their grades, and getting better grades and test scores promotes more positive self-views.}, } @article {pmid32362657, year = {2020}, author = {Brunelle, CL and Taghian, AG}, title = {Lymphoedema screening: setting the standard.}, journal = {British journal of cancer}, volume = {123}, number = {1}, pages = {1-2}, pmid = {32362657}, issn = {1532-1827}, support = {R01 CA139118/CA/NCI NIH HHS/United States ; P50CA08393//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; }, mesh = {Arm ; *Breast Neoplasms/diagnosis ; Female ; Humans ; *Lymphedema/diagnosis/epidemiology/etiology ; Prospective Studies ; Quality of Life ; Reference Standards ; }, abstract = {Existing literature which is changing practice should be scrutinised, in the interest of all women at risk for lymphoedema after breast cancer (BC). Bundred et al.'s prospective, multicentre trial of 1100 women made several solid findings, and novel screening recommendations presented may assist in incorporating lymphoedema screening into standard of care.}, } @article {pmid32359721, year = {2020}, author = {Dinnis, R and Bessudnov, A and Reynolds, N and Pate, A and Sablin, M and Sinitsyn, A}, title = {Response to Bataille et al.'s 'Technological differences between Kostenki 17/II (Spitsynskaya industry, Central Russia) and the Protoaurignacian: Reply to Dinnis et al. (2019)' [J. Hum. Evol. (2019), 102685].}, journal = {Journal of human evolution}, volume = {146}, number = {}, pages = {102792}, doi = {10.1016/j.jhevol.2020.102792}, pmid = {32359721}, issn = {1095-8606}, mesh = {*Archaeology ; Industry ; Russia ; *Technology ; }, } @article {pmid32357506, year = {2020}, author = {Zhang, T and Lee, J and Chu, TLA and Chen, C and Gu, X}, title = {Accessing Physical Activity and Health Disparities among Underserved Hispanic Children: The Role of Actual and Perceived Motor Competence.}, journal = {International journal of environmental research and public health}, volume = {17}, number = {9}, pages = {}, pmid = {32357506}, issn = {1660-4601}, mesh = {Child ; *Exercise ; *Health Status Disparities ; *Hispanic or Latino ; Humans ; Male ; Medically Underserved Area ; Motor Skills ; *Quality of Life ; Schools ; United States ; }, abstract = {Promoting physical activity (PA) and eliminating health disparities among underserved minority children is a public health priority. The main purpose of this study was to examine the relationship of actual motor competence (a set of object control skills) and perceived motor competence with PA participation and health-related quality of life (HRQoL) among underserved Hispanic children who were born in the U.S. Guided by Stodden et al.'s conceptual model, we tested the direct and indirect effects (mediational model) of actual motor competence on health-related outcomes (PA and HRQoL) through perceived motor competence. Participants were 215 underserved Hispanic children (Mage = 10.55 years, SD = 0.53 [age range 10-12]; 51.6% boys), recruited from four elementary schools in the southwestern U.S., who completed validated questionnaires assessing their perceived motor competence, PA, and HRQoL. Their actual motor skills were assessed using PE Metrics[TM]. After examining the associations among the variables, we tested the hypothesized model using structural equation modeling (SEM; AMOS 25). The hypothesized model indicated a good fit (χ[2]/df = 38.427/24 = 1.60 < 5; non-normed fit index (NFI) = 0.93; comparative fit index (CFI) = 0.968; root mean square error of approximation (RMSEA) = 0.053 [0.016, 0.083]). The effect of actual motor competence on PA and HRQoL was fully mediated by perceived motor competence. The findings demonstrated the mediating role of perceived motor competence between actual motor competence and health-related outcomes (PA and HRQoL) among underserved Hispanic children. The results highlight that actual motor competence significantly predicted underserved Hispanic children' perceived motor competence, which in turn positively predicted their PA and HRQoL. These findings have significant practical implications for future intervention strategies of randomized clinical trials in schools aimed at promoting PA and HRQoL and eliminating health disparities among underserved Hispanic children.}, } @article {pmid32346521, year = {2020}, author = {Bouya, S and Balouchi, A and Rafiemanesh, H and Amirshahi, M and Dastres, M and Moghadam, MP and Behnamfar, N and Shyeback, M and Badakhsh, M and Allahyari, J and Al Mawali, A and Ebadi, A and Dezhkam, A and Daley, KA}, title = {Global Prevalence and Device Related Causes of Needle Stick Injuries among Health Care Workers: A Systematic Review and Meta-Analysis.}, journal = {Annals of global health}, volume = {86}, number = {1}, pages = {35}, pmid = {32346521}, issn = {2214-9996}, mesh = {Cannula ; Dentists/statistics & numerical data ; Health Personnel/*statistics & numerical data ; Humans ; Needles ; Needlestick Injuries/*epidemiology ; Nurses/statistics & numerical data ; Occupational Injuries/*epidemiology ; Physicians/statistics & numerical data ; Prevalence ; Students, Nursing/statistics & numerical data ; }, abstract = {BACKGROUND: Healthcare workers (HCWs) suffer more than 2 million occupational needle-stick injuries (NSIs) annually.

GOAL: To determine the global prevalence and causes of NSIs among HCWs.

METHODS: In this systematic review and meta-analysis, three databases (PubMed, Web of science, and Scopus) were searched for reports from January 1, 2000 to December 31, 2018. The random effects model was used to determine the prevalence of NSIs among HCWs. Hoy et al.'s instrument was employed to evaluate the quality of the included studies.

FINDINGS: A total of 87 studies performed on 50,916 HCWs in 31 countries worldwide were included in the study. The one-year global pooled prevalence of NSIs among HCWs was 44.5% (95% CI: 35.7, 53.2). Highest prevalence of NSIs occurred in the South East Asia region at 58.2% (95%, CI: 36.7, 79.8). By job category, prevalence of NSIs was highest among dentists at 59.1% (95% CI: 38.8, 79.4), Hypodermic needles were the most common cause of NSIs at 55.1% (95% CI: 41.4, 68.9).

CONCLUSION: The current high prevalence of NSIs among HCWs suggests need to improve occupational health services and needle-stick education programs globally.}, } @article {pmid32336252, year = {2020}, author = {Chorlton, SD}, title = {Reanalysis of Alzheimer's brain sequencing data reveals absence of purported HHV6A and HHV7.}, journal = {Journal of bioinformatics and computational biology}, volume = {18}, number = {1}, pages = {2050012}, doi = {10.1142/S0219720020500122}, pmid = {32336252}, issn = {1757-6334}, mesh = {*Alzheimer Disease ; Brain ; Computational Biology ; *Herpesvirus 6, Human ; Humans ; }, abstract = {Readhead et al. recently reported in Neuron the detection and association of human herpesviruses 6A (HHV6A) and 7 (HHV7) with Alzheimer's disease by shotgun sequencing. I was skeptical of the specificity of their modified Viromescan bioinformatics method and subsequent analysis for numerous reasons. Using their supplementary data, the prevalence of variola virus, the etiological agent of the eradicated disease smallpox, can be calculated at 97.5% of their Mount Sinai Brain Bank dataset. Reanalysis of Readhead et al.'s data using highly sensitive and specific alternative methods finds no HHV7 reads in their samples; HHV6A reads were found in only 2 out of their top 15 samples sorted by reported HHV6A abundance. Finally, recreation of Readhead et al.'s modified Viromescan method identifies reasons for its low specificity.}, } @article {pmid32328505, year = {2020}, author = {AlAkhras, A and AlMessabi, A and Nsutebu, E}, title = {Response to Tande et al.'s Publication: "Association of a Remotely Offered Infectious Diseases eConsult Service With Improved Clinical Outcomes".}, journal = {Open forum infectious diseases}, volume = {7}, number = {4}, pages = {ofaa086}, pmid = {32328505}, issn = {2328-8957}, } @article {pmid32310802, year = {2021}, author = {Xiao, F}, title = {CED: A Distance for Complex Mass Functions.}, journal = {IEEE transactions on neural networks and learning systems}, volume = {32}, number = {4}, pages = {1525-1535}, doi = {10.1109/TNNLS.2020.2984918}, pmid = {32310802}, issn = {2162-2388}, abstract = {Evidence theory is an effective methodology for modeling and processing uncertainty that has been widely applied in various fields. In evidence theory, a number of distance measures have been presented, which play an important role in representing the degree of difference between pieces of evidence. However, the existing evidential distances focus on traditional basic belief assignments (BBAs) modeled in terms of real numbers and are not compatible with complex BBAs (CBBAs) extended to the complex plane. Therefore, in this article, a generalized evidential distance measure called the complex evidential distance (CED) is proposed, which can measure the difference or dissimilarity between CBBAs in complex evidence theory. This is the first work to consider distance measures for CBBAs, and it provides a promising way to measure the differences between pieces of evidence in a more general framework of complex plane space. Furthermore, the CED is a strict distance metric with the properties of nonnegativity, nondegeneracy, symmetry, and triangle inequality that satisfies the axioms of a distance. In particular, when the CBBAs degenerate into classical BBAs, the CED will degenerate into Jousselme et al.'s distance. Therefore, the proposed CED is a generalization of the traditional evidential distance, but it has a greater ability to measure the difference or dissimilarity between pieces of evidence. Finally, a decision-making algorithm for pattern recognition is devised based on the CED and is applied to a medical diagnosis problem to illustrate its practicability.}, } @article {pmid32304261, year = {2020}, author = {Hoeeg, D and Christensen, U and Grabowski, D}, title = {Intra-familial health polarisation: how diverse health concerns become barriers to health behaviour change in families with preschool children and emerging obesity.}, journal = {Sociology of health & illness}, volume = {42}, number = {6}, pages = {1243-1258}, doi = {10.1111/1467-9566.13091}, pmid = {32304261}, issn = {1467-9566}, mesh = {Child, Preschool ; Health Behavior ; *Health Knowledge, Attitudes, Practice ; Humans ; Obesity ; Overweight ; Parents ; *Pediatric Obesity ; }, abstract = {In a disadvantaged rural area in Denmark, severe challenges have been identified concerning overweight and obesity in families with preschool-age children. The present paper examines how families with young children and emerging obesity issues perceive 'healthy living' and barriers to practising it. Using data from qualitative workshops with families and professionals working with them, we reveal health perceptions and related family dynamics. Drawing on P. Bourdieu's theory of habitus and 'tastes of necessity', K.L. Frohlich et al.'s notion of 'collective lifestyles' and E. Lindbladh and C. H. Lyttken's theory of preconditions for health behaviour change and reactions to risk-related information, we analyse how risk perceptions and related health practices within the families are influenced by the local contexts in the disadvantaged area under study. Despite shared perceptions of 'healthy living', we found that diverse health-risk perceptions created family dynamics in which parents performed opposed health behaviours, which became a huge barrier to becoming a healthier family. Based on our theoretical approach, we propose that risk perceptions and reactions are highly context dependent, as illustrated in both micro-contexts (family dynamics) and the macro-context (the disadvantaged area).}, } @article {pmid32304255, year = {2020}, author = {Shover, CL}, title = {Commentary on Larance et al. (2020): Priorities and concerns of people who use opioids are key to scaling up XR-buprenorphine.}, journal = {Addiction (Abingdon, England)}, volume = {115}, number = {7}, pages = {1306-1307}, pmid = {32304255}, issn = {1360-0443}, support = {T32 DA035165/DA/NIDA NIH HHS/United States ; T32DA035165/DA/NIDA NIH HHS/United States ; }, mesh = {Analgesics, Opioid ; Australia ; *Buprenorphine ; Humans ; Opiate Substitution Treatment ; *Opioid-Related Disorders ; }, abstract = {Larence et al.’s findings have key implications for XR-buprenorphine guidelines as it becomes available internationally. These are to embrace less-onerous dosing schedules, to consider incorporating into standard-of-care an option to supplement with transmucosal buprenorphine between injections, and to investigate what possibilities XR-buprenorphine opens up for patients wanting to taper off opioid agonist treatment.}, } @article {pmid32301931, year = {2020}, author = {Figuracion, KCF}, title = {Response to "Built and Natural Environment Barriers and Facilitators to Physical Activity in Rural, Suburban, and Small Urban Neighborhoods".}, journal = {Oncology nursing forum}, volume = {47}, number = {3}, pages = {255-256}, pmid = {32301931}, issn = {1538-0688}, support = {T32 NR016913/NR/NINR NIH HHS/United States ; }, mesh = {*Cancer Survivors ; Exercise ; Humans ; *Residence Characteristics ; Rural Population ; }, abstract = {DeGuzman et al. (2019) should be commended for their article "Built and Natural Environment Barriers and Facilitators to Physical Activity in Rural, Suburban, and Small Urban Neighborhoods." The work is a meaningful contribution to the oncology field, given the health disparity among patients with cancer living in rural and suburban communities. Nurses need to be part of the larger conversation and advocate for patients through policy reform that supports access to an equitable built environment. DeGuzman et al.'s (2019) article starts this conversation. In this letter, I wish to build on that initial conversation by deepening the discussion of built environment and costs as significant barriers to physical activity in cancer survivors.}, } @article {pmid32291973, year = {2020}, author = {Zhang, Y and Zhou, Y and Mao, F and Yao, R and Sun, Q}, title = {Ki-67 index, progesterone receptor expression, histologic grade and tumor size in predicting breast cancer recurrence risk: A consecutive cohort study.}, journal = {Cancer communications (London, England)}, volume = {40}, number = {4}, pages = {181-193}, pmid = {32291973}, issn = {2523-3548}, mesh = {Adult ; Breast Neoplasms/*genetics/pathology ; Cohort Studies ; Female ; Humans ; Ki-67 Antigen/*metabolism ; Middle Aged ; Neoplasm Recurrence, Local ; Receptors, Progesterone/*metabolism ; Risk Factors ; Young Adult ; }, abstract = {BACKGROUND: The 21-gene recurrence score (RS) assay has been recommended by major guidelines for treatment decision in hormone receptor (HR)-positive early breast cancer (EBC). However, the genomic assay is not accessible and affordable worldwide. Alternatively, an increasing number of studies have shown that traditional immunohistochemistry (IHC) can partially or even completely replace the role of the 21-gene genomic assay. Here, we developed and validated a predictive model (IHC3 model) combining the Ki-67 index, progesterone receptor (PR) expression, histologic grade, and tumor size to predict the recurrence risk of HR-positive EBC.

METHODS: The data from 389 patients (development set) with HR-positive, human epidermal growth factor receptor 2-negative, lymph node non-metastasized invasive breast cancer were used to construct the IHC3 model based on the Surexam[®] 21-gene RS and the TAILORx clinical trial criteria. An additional 146 patients with the same characteristics constituted the validation set. The predictive accuracy of the IHC3 model was compared with that of Orucevic et al.'s nomogram. Invasive disease-free survival (IDFS) was analyzed in the IHC3 predictive low-recurrence risk (pLR) group and the predictive high-recurrence risk (pHR) group. The Pearson chi-square test, Fisher exact test, and log-rank test were used for analysis.

RESULTS: The pLR and pHR group could be easily stratified using the decision tree model without network dependence. The accuracies of the IHC3 model were 86.1% in the development set and 87.7% in the validation set. The predictive accuracy of the IHC3 model and Orucevic et al.'s nomogram for the whole cohort was 86.5% and 86.9%, respectively. After a 52-month of median follow-up, a significant difference was found in IDFS between of the IHC3 pLR and the pHR groups (P = 0.001) but not in the IDFS between the low- and high-recurrence risk groups according to the Surexam® 21-gene RS and the TAILORx clinical trial criteria (P = 0.556) or 21-gene binary RS group (P = 0.511).

CONCLUSIONS: The proposed IHC3 model could reliably predict low and high recurrence risks in most HR-positive EBC patients. This easy-to-use predictive model may be a reliable replacement for the 21-gene genomic assay in patients with EBC who have no access to or cannot afford the 21-gene genomic assay.}, } @article {pmid32281898, year = {2022}, author = {Nobes, G and Panagiotaki, G and Malvaso, C and Klevens, J}, title = {Physical Abuse of Children by Stepfathers in Colombia.}, journal = {Journal of interpersonal violence}, volume = {37}, number = {7-8}, pages = {NP5747-NP5773}, doi = {10.1177/0886260520912585}, pmid = {32281898}, issn = {1552-6518}, mesh = {Adolescent ; Child ; *Child Abuse ; Colombia/epidemiology ; Fathers ; Female ; Humans ; Male ; Mothers ; *Physical Abuse ; }, abstract = {Evolutionary psychologists claim that stepparents perpetrate substantially more child physical abuse than genetic parents, and that they do so because they are less invested in genetically unrelated children. The objective of this study was to examine these claims by investigating whether, and why, fathers in a Colombian sample physically abused their stepchildren more than their genetic children. Fathers (N = 86) and their partners living in Bogotá were interviewed by Klevens et al. Half of the fathers had been reported to authorities for child physical abuse, the other half were matched controls. Secondary analysis was conducted of Klevens et al.'s data. Hypotheses from the evolutionary and ecological accounts of child maltreatment were tested using logistic and ordinal regression. Both the prevalence and the frequency of physical abuse by stepfathers were considerably greater than those of genetic fathers. Several indicators of adversity-including parental youth and experience of abuse, fathers' chronic stress, and mothers' poor communication with the child-were associated with both abuse and stepparenthood. Models including these variables indicated that they accounted for much of the stepfathers' higher rates of abuse. Consistent with the ecological account, much of the stepfathers' greater prevalence and frequency of abuse in this sample is likely to have resulted from confounding variables, rather than from the step relationship per se.}, } @article {pmid32275985, year = {2020}, author = {Joshi, S and Jan, KM and Rumschitzki, D}, title = {Pre-atherosclerotic flow and oncotically active solute transport across the arterial endothelium.}, journal = {Journal of theoretical biology}, volume = {499}, number = {}, pages = {110275}, pmid = {32275985}, issn = {1095-8541}, support = {R01 HL067383/HL/NHLBI NIH HHS/United States ; }, mesh = {Aorta ; Arteries ; *Atherosclerosis ; Endothelium, Vascular ; Humans ; Lipoproteins, LDL ; *Models, Cardiovascular ; }, abstract = {Atherosclerosis starts with transmural (transwall) pressure-driven advective transport of blood-borne low-density lipoprotein (LDL) cholesterol across rare endothelial cell (EC) monolayer leaks into the arterial subendothelial intima (SI) wall layer where they can spread, bind to extracellular matrix and seed lesions. The local SI LDL concentration, which governs LDL's binding kinetics, depends on the overall diluting transmural liquid flow. Transmural pressures typically compress the SI at physiological pressures, which keeps this flow low. Nguyen et al. (2015) showed that aortic ECs express the water channel protein aquaporin-1 (AQP1) and the transEC (δP) portion of the transmural (ΔP) pressure difference drives, in parallel, water across AQP1s and plasma across interEC junctions. Since the lumen is isotonic, selective AQP1-mediated water flow should quickly render the ECs' lumen side hypertonic and the SI hypotonic; resulting transEC oncotic pressure differences, δπ, should oppose δP and quickly halt transEC flow. Yet Nguyen et al.'s (2015) transAQP1 flows persist for hours. To resolve this paradox, we extend our fluid filtration theory Joshi et al. (2015) to include mass transfer for oncotically active solutes like albumin. This addition nonlinearly couples mass transfer, fluid flow and wall mechanics. We simultaneously solve these problems at steady state. Surprisingly it finds that media layer filtration causes steady SI to exceed EC glycocalyx albumin concentration. Thus δπ reinforces rather than opposes δP, i.e., it sucks water from, rather than pushing water into the lumen from the SI. Endothelial AQP1s raise the overall driving force for flow across the EC above δP, most significantly at pressures too low to compress the SI, and they increase the ΔP needed for SI compression. This suggests the intriguing possibility that increasing EC AQP1 expression can raise this requisite compression pressure to physiological values. That is, increasing EC AQP1 may decompress the SI at physiological pressures, which would significantly increase SI thickness, flow and subsequently SI LDL dilution. This could retard LDL binding and delay preatherosclerotic lesion onset. The model also predicts that glycocalyx-degrading enzymes decrease overall transEC driving forces and thus lower, not raise, transmural water flux.}, } @article {pmid32273901, year = {2020}, author = {Wang, Y and Kou, Y and Meng, D}, title = {Network Structure Analysis Identifying Key Genes of Autism and Its Mechanism.}, journal = {Computational and mathematical methods in medicine}, volume = {2020}, number = {}, pages = {3753080}, pmid = {32273901}, issn = {1748-6718}, mesh = {Animals ; Autistic Disorder/etiology/*genetics/physiopathology ; Brain/physiopathology ; Case-Control Studies ; Child ; Computational Biology ; Databases, Genetic/statistics & numerical data ; Female ; Gene Expression Profiling/statistics & numerical data ; *Gene Regulatory Networks ; Humans ; Male ; Mice ; Mice, Knockout ; Molecular Sequence Annotation ; Nerve Tissue Proteins/deficiency/genetics ; Signal Transduction/genetics ; Synaptic Transmission/genetics ; Transcriptome ; }, abstract = {Identifying the key genes of autism is of great significance for understanding its pathogenesis and improving the clinical level of medicine. In this paper, we use the structural parameters (average degree) of gene correlation networks to identify genes related to autism and study its pathogenesis. Based on the gene expression profiles of 82 autistic patients (the experimental group, E) and 64 healthy persons (the control group, C) in NCBI database, spearman correlation networks are established, and their average degrees under different thresholds are analyzed. It is found that average degrees of C and E are basically separable at the full thresholds. This indicates that there is a clear difference between the network structures of C and E, and it also suggests that this difference is related to the mechanism of disease. By annotating and enrichment analysis of the first 20 genes (MD-Gs) with significant difference in the average degree, we find that they are significantly related to gland development, cardiovascular development, and embryogenesis of nervous system, which support the results in Alter et al.'s original research. In addition, FIGF and CSF3 may play an important role in the mechanism of autism.}, } @article {pmid32272795, year = {2020}, author = {Wilson, MP and Low, G and Katlariwala, P and Jacques, L and Jack, AS}, title = {Ultrasound for Neurogenic Thoracic Outlet Obstruction Remains Theoretical.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {10}, number = {4}, pages = {}, pmid = {32272795}, issn = {2075-4418}, abstract = {We enjoyed reading Povleson et al.'s review entitled "Diagnostic thoracic outlet syndrome: current approaches and future directions" [...].}, } @article {pmid32271788, year = {2020}, author = {Wu, B and Wang, C and Yao, H}, title = {Security analysis and secure channel-free certificateless searchable public key authenticated encryption for a cloud-based Internet of things.}, journal = {PloS one}, volume = {15}, number = {4}, pages = {e0230722}, pmid = {32271788}, issn = {1932-6203}, mesh = {Algorithms ; Cloud Computing/*standards ; Computer Security/*standards ; Confidentiality ; Data Management/methods/organization & administration/standards ; Efficiency, Organizational ; Electronic Health Records/organization & administration/standards ; Health Information Exchange/standards ; Humans ; *Information Storage and Retrieval/methods/standards ; *Internet of Things/organization & administration/standards ; Outsourced Services/organization & administration/standards ; *Public Sector/organization & administration/standards ; Wireless Technology/organization & administration/standards ; }, abstract = {With the rapid development of informatization, an increasing number of industries and organizations outsource their data to cloud servers, to avoid the cost of local data management and to share data. For example, industrial Internet of things systems and mobile healthcare systems rely on cloud computing's powerful data storage and processing capabilities to address the storage, provision, and maintenance of massive amounts of industrial and medical data. One of the major challenges facing cloud-based storage environments is how to ensure the confidentiality and security of outsourced sensitive data. To mitigate these issues, He et al. and Ma et al. have recently independently proposed two certificateless public key searchable encryption schemes. In this paper, we analyze the security of these two schemes and show that the reduction proof of He et al.'s CLPAEKS scheme is incorrect, and that Ma et al.'s CLPEKS scheme is not secure against keyword guessing attacks. We then propose a channel-free certificateless searchable public key authenticated encryption (dCLPAEKS) scheme and prove that it is secure against inside keyword guessing attacks under the enhanced security model. Compared with other certificateless public key searchable encryption schemes, this scheme has higher security and comparable efficiency.}, } @article {pmid32257445, year = {2020}, author = {Bertholet, O and Pasquier, M and Christes, E and Wirths, D and Carron, PN and Hugli, O and Dami, F}, title = {Lights and Siren Transport and the Need for Hospital Intervention in Nontrauma Patients: A Prospective Study.}, journal = {Emergency medicine international}, volume = {2020}, number = {}, pages = {2651624}, pmid = {32257445}, issn = {2090-2840}, abstract = {BACKGROUND: The use of lights and siren transport (LST) has been a matter of debate because of the short time savings and well-established increased risks for Emergency Medical Services (EMS) and bystanders. Time-critical hospital intervention (TCHI) denotes urgently needed procedures that cannot be performed properly in an out-of-hospital setting. Since 2013, rapid transportation from the field, fast-track, is currently used for patients with acute ST-elevation myocardial infarction, suspicion of acute stroke and out-of-hospital cardiac arrest. The aim of this study was to determine whether the use of LST was associated with the realization of TCHI for nontrauma cases within 15 minutes of hospital arrival, to quantify overtriage (LST without TCHI) and to identify the predictors of TCHI.

METHODS: This is a monocentric prospective observational study of nontrauma patients transported by ambulance. Based on Ross et al.'s work in 2016 on trauma patients, TCHI procedures were developed by the study team. Descriptive statistics were used to determine whether the use of LST was associated with the realization of TCHI. Multivariable analyses determined the predictors of TCHI and compared clinical outcomes.

RESULTS: On the 324 patients included, 67 (20.7%) benefitted from LST, with 40 (59.7%) receiving TCHI (p < 0.001). The overtriage rate was 40.3%. The most common medical TCHI was the fast-track (65.2% of all TCHI). LST was predictive of the need for TCHI (p < 0.001), as was the clinical condition of the patient and also when EMS providers expected TCHI.

CONCLUSIONS: A majority of the LST benefitted from TCHI with an overtriage rate of 40%. To reduce the rate of overtriage (LST without TCHI), LST should mainly be used for fast-track and when TCHI is expected by the EMS providers.}, } @article {pmid32250144, year = {2020}, author = {Chan, L and Zubrod, A and Woodard, SR and Conway, LG}, title = {Identity leadership is manifested via integrative complexity: Comment on Haslam et al. (2019).}, journal = {The American psychologist}, volume = {75}, number = {3}, pages = {403-405}, doi = {10.1037/amp0000618}, pmid = {32250144}, issn = {1935-990X}, mesh = {Humans ; Leadership ; *Prisoners ; *Prisons ; }, abstract = {Haslam, Reicher, and Van Bavel (2019) convincingly argued that experimenters in the Stanford Prison Experiment (SPE) influenced prisoners via identity-based communication. However, Haslam et al. focused on direct mechanisms of identity communication. In our comment, we discuss a less direct-but potentially equally important-communication mechanism by which leaders in the SPE may have influenced followers: integrative complexity. This consideration of integrative complexity not only bolsters the basic point of Haslam et al.'s article also provides new avenues for understanding the mechanisms by which leader identity processes work in cases like the SPE. (PsycInfo Database Record (c) 2020 APA, all rights reserved).}, } @article {pmid32246731, year = {2020}, author = {Hansen, FT and Jørgensen, LB}, title = {A contribution to the ontology of the Fundamentals of Care framework from a wonder-based approach.}, journal = {Journal of clinical nursing}, volume = {29}, number = {11-12}, pages = {1797-1807}, doi = {10.1111/jocn.15272}, pmid = {32246731}, issn = {1365-2702}, mesh = {Humans ; Nurse's Role ; *Nurse-Patient Relations ; Nursing Methodology Research ; Philosophy ; }, abstract = {AIM AND OBJECTIVES: To critically discuss the ontological framework of Fundamentals of Care (FoC), as developed by Uhrenfeldt, et al. (2018), Journal of Clinical Nursing, 27, 3197-3204; to suggest theoretical improvements by taking a wonder-based approach; and to show how this approach can be applied in healthcare sectors.

BACKGROUND: Based on a critical discussion of a discursive study on the ontology of FoC, studies in phenomenology of wonder and two action research projects involving "Wonder Labs," this article discusses whether the ontology and reflective practices behind FoC can be qualified further by an existential phenomenology of wonder and with practices of "Wonder Labs."

DESIGN: This is a discursive study critically discussing Uhrenfeldt et al.'s primary focus on dyadic and relational openness and person-oriented attentiveness in a nurse-patient relationship. This is done by unfolding the phenomenology of wonder and wonder experiences at a hospice and a hospital, and by critically examining the psychologically influenced interpretation of Heidegger.

CONCLUSION: The first attempts by Uhrenfeldt et al. to identify the philosophical roots and ontology of FoC by pointing to existential phenomenology and philosophy are acknowledged. However, in this article, we further elaborate this attempt by focusing on the phenomenology of wonder. We show that Heidegger speaking about "existential homecoming" referred to a philosophical practice focusing on the resonance with being, rather than on interpersonal and psychological relations. In conclusion, the article recognises the importance of integrating these two approaches described on the one hand as a person-oriented and lifeworld-led approach, and on the other hand as a being- and phenomenon-oriented approach to the nurse-patient relationship.

To be open to the "musicality" of the being dimension, as the core values of FoC, a wonder-based approach to value clarifications and phenomenological dialogues is pivotal for the presence of openness, trust and attentiveness of the nurse-patient relationship. The practices of the "Wonder Lab" may be an approach for training nurses in hearing the call of this "ontological resonance."}, } @article {pmid32239490, year = {2020}, author = {Rosbakh, S and Baskin, CC and Baskin, JM}, title = {Nikolaeva et al.'s reference book on seed dormancy and germination.}, journal = {Ecology}, volume = {101}, number = {7}, pages = {e03049}, doi = {10.1002/ecy.3049}, pmid = {32239490}, issn = {1939-9170}, mesh = {Biological Evolution ; *Germination ; Humans ; *Plant Dormancy ; Reference Books ; Seeds ; }, abstract = {Despite the recent advances in seed science research, information on seed dormancy and germination traits is still missing for many lineages of the seed plants. We translated and digitized a huge data set on seed dormancy and germination from the Reference Book On Dormant Seed Germination by M. Nikolaeva, M. Razumova, and V. Gladkova published in Russian in 1985 and previously not readily accessible to the great majority of people in the international scientific community interested in seeds. The data set contains information on the seed dormancy classification (sensu Nikolaeva et al., 1985; Baskin and Baskin, 2004), dormancy-breaking conditions/germination, and for some of the included species storage behaviour, of seeds of nearly 3000 gymnosperm and angiosperm species from 843 genera and 164 families occurring worldwide. Additionally, the data set contains about 550 references, many of them unknown to seed scientists, to seed ecology research conducted between 1926 and 1985. The data set should be of value to applied, basic, and theoretical plant biologists, ecologists, and evolutionary biologists interested in the various aspects of regeneration of plants from seeds. There are no copyright or proprietary restrictions for research or teaching purposes. The originator of the data would appreciate notification when and how the data are used. When used in published analyses, this paper should be referred to as the data source.}, } @article {pmid32239352, year = {2020}, author = {Maggi, G and D'Iorio, A and Di Meglio, D and Vinciguerra, A and Amboni, M and Vitale, C and Santangelo, G}, title = {The role of the motor subtypes on the relationship between anxiety and cognitive dysfunctions in Parkinson's disease.}, journal = {Journal of neural transmission (Vienna, Austria : 1996)}, volume = {127}, number = {6}, pages = {893-898}, doi = {10.1007/s00702-020-02179-x}, pmid = {32239352}, issn = {1435-1463}, mesh = {Anxiety/etiology ; *Cognitive Dysfunction/etiology ; *Gait Disorders, Neurologic ; Humans ; Neuropsychological Tests ; *Parkinson Disease/complications ; }, abstract = {Anxiety is a common neuropsychiatric symptom in Parkinson's disease (PD). Until now, anxiety has been consistently related to cognitive deficits and severity of motor symptoms, whereas the association between anxiety and motor subtypes (TD-PD, tremor dominant and PIGD-PD, postural instability/gait disturbances dominant) revealed contrasting results. The present study aims to investigate the relationship between PD motor subtypes and anxiety and to explore whether the relationship between anxiety and cognitive deficits occurs in a specific PD motor subtype. Consecutive PD outpatients were recruited and divided into TD-PD and PIGD-PD groups according to Jankovic et al.'s criteria. All participants underwent a neuropsychological battery to evaluate anxiety, apathy, the global cognitive functioning, memory abilities, executive and visuo-constructional functions. Thirty-six patients with TD-PD and 35 patients with PIGD-PD were enrolled. The two groups did not differ on demographical and clinical variables. As for the severity of anxiety, no significant difference between the two groups was found. Regression analysis revealed that higher anxiety score was associated with poorer performance on constructional visuospatial test in both TD-PD and PIGD-PD. Clinical variables were not associated with anxiety in the two groups. Our findings indicated that the severity of anxiety was not associated with any PD motor subtypes. Moreover, regression analysis revealed that impaired visuo-constructional abilities are related to anxiety independently of PD motor subtypes. Since altered fronto-parietal network might be one of the pathogenetic mechanisms underpinning anxiety and constructional visuospatial deficits, the treatment of cognitive dysfunctions might reduce anxious symptoms.}, } @article {pmid32227255, year = {2020}, author = {Rana, S and Mishra, D}, title = {Efficient and Secure Attribute Based Access Control Architecture for Smart Healthcare.}, journal = {Journal of medical systems}, volume = {44}, number = {5}, pages = {97}, pmid = {32227255}, issn = {1573-689X}, mesh = {Cloud Computing/*standards ; Computer Security/*standards ; Confidentiality/*standards ; Electronic Health Records/organization & administration ; Humans ; Information Systems/*organization & administration/standards ; }, abstract = {The smart health medical system is expected to enhance the quality of health care services significantly. These system keeps patients related record and provides the services over the insecure public channel which may cause data security and privacy concerns in a smart health system. On the other hand, ciphertext attribute-based encryption(CP-ABE) provides possible encrypted data security. There are some security flaws in CP-ABE, where the existing access policies are in the cleartext form for accessing encrypted sensitive data. On the other hand, it supports the small attribute universe, which restricts the practical deployments of CP-ABE. Moreover, outsider adversary observed the communication, which also creates a serious threat to CP-ABE model. To overcome security and privacy risk, efficient access control have been designed and devolved for medical services. Although we also demonstrate the security analysis of Zhang et al.'s scheme, which is vulnerable to inefficient security proof and man in the middle attack. In the proposed scheme, we proposed an efficient and security preserve scheme to overcome the weaknesses of Zhang's et al.'s system. The protocol satisfies the attribute values of the medical user with hidden access policies. It has been proved under the standard model, which ensure the security of the protocol. Moreover, performance analysis comparison shows that the proposed scheme is more efficient than the existing one.}, } @article {pmid32212662, year = {2020}, author = {Thonnekottu, D and Chatterjee, D}, title = {CRISPR-Cas9 Genome Interrogation: A Facilitated Subdiffusive Target Search Strategy.}, journal = {The journal of physical chemistry. B}, volume = {124}, number = {16}, pages = {3271-3282}, doi = {10.1021/acs.jpcb.0c00086}, pmid = {32212662}, issn = {1520-5207}, mesh = {Animals ; *CRISPR-Cas Systems/genetics ; *Clustered Regularly Interspaced Short Palindromic Repeats ; Gene Editing ; Genetic Engineering ; Genome ; }, abstract = {The functional application of RNA-guided CRISPR-associated Cas9 protein, a bacterial immune system-based protein complex, via which in vivo, highly specific, and well-regulated, gene-editing processes are being monitored at an unprecedented level, has led to remarkable progress in genetic engineering and technology. The complicated in vivo process of genome interrogation followed by gene editing by the Cas9 complex was recently reported by Knight et al. (Science, 2015, 350, 823-826) using an elegant single-particle tracking method, aided by the two-photon fluorescence correlation spectroscopic technique. In contrast to the usually observed fast target-searching and protein-binding events in biophysical systems, an interesting slow genome-interrogation process by the RNA-guided CRISPR-Cas9 system through a crowded chromatin environment of a mammalian cell has been revealed in Knight et al.'s study. Motivated by this experiment, in this paper, we provide a generalized theoretical framework to capture this particular target-searching mechanism of the CRISPR-Cas9 protein complex. We show that an analysis on the basis of 3D subdiffusion under a cylindrical volume, created by several nonspecific off-target interactions from the DNA strands, can capture the essential details of the process. Moreover, on the basis of this model, we quantify the dynamics of this process and estimate the survival probability, first passage time, and the intensity correlation function of the tagged proteins of the experiment. The results from our theoretical predictions are found to be consistent with the experimental observations, and hence, seem to provide a plausible microscopic picture of the process.}, } @article {pmid32210198, year = {2020}, author = {Sajib, MQU and Wang, T}, title = {Estimation of Land Surface Temperature in an Agricultural Region of Bangladesh from Landsat 8: Intercomparison of Four Algorithms.}, journal = {Sensors (Basel, Switzerland)}, volume = {20}, number = {6}, pages = {}, pmid = {32210198}, issn = {1424-8220}, abstract = {The presence of two thermal bands in Landsat 8 brings the opportunity to use either one or both of these bands to retrieve Land Surface Temperature (LST). In order to compare the performances of existing algorithms, we used four methods to retrieve LST from Landsat 8 and made an intercomparison among them. Apart from the direct use of the Radiative Transfer Equation (RTE), Single-Channel Algorithm and two Split-Window Algorithms were used taking an agricultural region in Bangladesh as the study area. The LSTs retrieved in the four methods were validated in two ways: first, an indirect validation against reference LST, which was obtained in the Atmospheric and Topographic CORection (ATCOR) software module; second, cross-validation with Terra MODerate Resolution Imaging Spectroradiometer (MODIS) daily LSTs that were obtained from the Application for Extracting and Exploring Analysis Ready Samples (A ρ ρ EEARS) online tool. Due to the absence of LST-monitoring radiosounding instruments surrounding the study area, in situ LSTs were not available; hence, validation of satellite retrieved LSTs against in situ LSTs was not performed. The atmospheric parameters necessary for the RTE-based method, as well as for other methods, were calculated from the National Centers for Environmental Prediction (NCEP) database using an online atmospheric correction calculator with MODerate resolution atmospheric TRANsmission (MODTRAN) codes. Root-mean-squared-error (RMSE) against reference LST, as well as mean bias error against both reference and MODIS daily LSTs, was used to interpret the relative accuracy of LST results. All four methods were found to result in acceptable LST products, leaving atmospheric water vapor content (w) as the important determinant for the precision result. Considering a set of several Landsat 8 images of different dates, Jiménez-Muñoz et al.'s (2014) Split-Window algorithm was found to result in the lowest mean RMSE of 1 . 19 ∘ C . Du et al.'s (2015) Split-Window algorithm resulted in mean RMSE of 1 . 50 ∘ C . The RTE-based direct method and the Single-Channel algorithm provided the mean RMSE of 2 . 47 ∘ C and 4 . 11 ∘ C , respectively. For Du et al.'s algorithm, the w range of 0 . 0 to 6 . 3 g / c m 2 was considered, whereas for the other three methods, w values as retrieved from the NCEP database were considered for corresponding images. Land surface emissivity was retrieved through the Normalized Difference Vegetation Index (NDVI)-threshold method. This intercomparison study provides an LST retrieval methodology for Landsat 8 that involves four algorithms. It proves that (i) better LST results can be obtained using both thermal bands of Landsat 8; (ii) the NCEP database can be used to determine atmospheric parameters using the online calculator; (iii) MODIS daily LSTs from A ρ ρ EEARS can be used efficiently in cross-validation and intercomparison of Landsat 8 LST algorithms; and (iv) when in situ LST data are not available, the ATCOR-derived LSTs can be used for indirect verification and intercomparison of Landsat 8 LST algorithms.}, } @article {pmid32205823, year = {2020}, author = {Zhao, F and Tang, B and Hu, C and Wang, B and Wang, Y and Zhang, L}, title = {The impact of frailty on posttraumatic outcomes in older trauma patients: A systematic review and meta-analysis.}, journal = {The journal of trauma and acute care surgery}, volume = {88}, number = {4}, pages = {546-554}, doi = {10.1097/TA.0000000000002583}, pmid = {32205823}, issn = {2163-0763}, mesh = {Aged ; Aged, 80 and over ; Frail Elderly/statistics & numerical data ; Frailty/*complications/diagnosis/mortality ; Geriatric Assessment ; Hospital Mortality ; Humans ; Middle Aged ; Patient Discharge/*statistics & numerical data ; Patient Readmission/statistics & numerical data ; Postoperative Complications/*epidemiology/etiology ; Risk Factors ; Skilled Nursing Facilities/statistics & numerical data ; Surgical Procedures, Operative/*adverse effects ; Wounds and Injuries/complications/*mortality/surgery ; }, abstract = {BACKGROUND: Frailty is a risk factor for mortality among the elderly. However, evidence from longitudinal studies linking trauma and frailty is fragmented, and a comprehensive analysis of the relationship between frailty and adverse outcomes is lacking. Therefore, we conducted a systematic review and meta-analysis to examine whether frailty is predictive of posttraumatic results including mortality, adverse discharge, complications, and readmission in trauma patients.

METHODS: This systematic review was registered with the PROSPERO international prospective register of systematic reviews. Articles in PubMed, Embase, and Web of Science databases from January 1, 1990, to October 31, 2019, were systematically searched. Articles in McDonald et al.'s study (J Trauma Acute Care Surg. 2016;80(5):824-834) and Cubitt et al.'s study (Injury 2019;50(11):1795-1808) were included for studies evaluating the association between frailty and outcomes in trauma patients. Cohort studies, both retrospective and prospective, were included. Study population was patients suffering trauma injuries with an average age of 50 years and older. Multivariate adjusted odds ratios (ORs) were calculated through a random-effects model, and the Newcastle-Ottawa Quality Assessment Scale was used to assess studies.

RESULTS: We retrieved 11,313 entries. Thirteen studies including seven prospective and six retrospective cohort studies involving 50,348 patients were included in the meta-analysis. Frailty was a significant predictor of greater than 30-day mortality (OR, 2.41; 95% confidence interval [CI], 1.17-4.95; I = 88.1%), in-hospital and 30-day mortality (OR, 4.05; 95% CI, 2.02-8.11; I = 0%), postoperative complications (OR, 2.23; 95% CI, 1.34-3.73; I = 78.2%), Clavien-Dindo IV complications (OR, 4.16; 95% CI, 1.70-10.17; I = 0%), adverse discharge (OR, 1.80; 95% CI, 1.15-2.84; I = 78.6%), and readmission (OR, 2.16; 95% CI, 1.19-3.91; I = 21.5%) in elderly trauma patients. Subgroup analysis showed that prospective studies (OR, 3.06; 95% CI, 1.43-6.56) demonstrated a greater correlation between frailty and postoperative complications.

CONCLUSION: Frailty has significant adverse impacts on the occurrence of posttraumatic outcomes. Further studies should focus on interventions for patients with frailty. Given the number of vulnerable elderly trauma patients grows, further studies are needed to determine the accuracy of these measures in terms of trauma outcomes.

LEVEL OF EVIDENCE: Systematic review and meta-analysis, level IV.}, } @article {pmid32189841, year = {2020}, author = {Kamboj, S and Salaria, SK}, title = {Efficacy of liquid nitrogen and electrocautery assisted gingival depigmentation in term of patient's perception, histological wound healing - A randomized triple blind clinical trial.}, journal = {Journal of Indian Society of Periodontology}, volume = {24}, number = {2}, pages = {135-144}, pmid = {32189841}, issn = {0972-124X}, abstract = {BACKGROUND: Hyper-melanin pigmentation of the gingiva (GMP) is one of the imperative contributory factors for smile-sensitive individuals. Numerous gingival depigmentation (GD) procedures have been attempted in the literature to evaluate the clinical outcome mostly. Hence, a randomized clinical-histopathological triple-blinded trial was planned to evaluate the pain experienced by the patient, gingival wound healing, and density of melanocytes following liquid nitrogen-assisted GD (LNAGD) and electrocautery-assisted GD (ECAGD) procedures.

MATERIALS AND METHODS: Thirty-two arches with bilateral physiologic labial/buccal GMP extending from distal aspect tooth #14-24 and #34-44 in 16 healthy individuals were selected and were equally treated with LNAGD and ECAGD techniques. Dummett oral pigmentation index and Hedin melanin index were evaluated at baseline and 3 months' postoperatively (PO). The visual analog scale was utilized for the intensity of pain assessment at baseline (immediately after treatment) and 1[st] day and 7[th] day PO. Histological wound healing and density of melanocytes were evaluated using Gal et al.'s wound-healing assessment index and Patsakas et al.'s criterion, at baseline (0), 8, 24, 72, and 96 h; 1[st], 2[nd], 3[rd], and 4[th] week; and 3 months and at 0 and 3 months' PO, respectively. Statistical analysis was done using one-way ANOVA, post hoc Tukey, unpaired, and paired "t" test.

RESULTS: Both groups showed a statistically significant influence on the parameters evaluated.

CONCLUSION: The LNAGD had a substantial superior result in terms of early wound healing, reduction in density of melanocytes, reduction in pain experienced by the patient, with reduction and delay in the recurrence of GMP.}, } @article {pmid32182486, year = {2020}, author = {Harpur, RA and Haddon, SJ}, title = {Typologies of postnatal support and breastfeeding at two months in the UK: Research participant commentary.}, journal = {Social science & medicine (1982)}, volume = {252}, number = {}, pages = {112911}, doi = {10.1016/j.socscimed.2020.112911}, pmid = {32182486}, issn = {1873-5347}, mesh = {Female ; Humans ; Infant ; *Mothers ; United Kingdom ; }, abstract = {Emmott et al. (2020) presented in this journal an analysis of different types of postnatal support that mothers in the UK experience and their relationship to breastfeeding status at two months. This paper is a commentary by two participants in the study. It draws on the research literature alongside recent lived experiences of breastfeeding and formula feeding in the UK to question and expand on Emmott et al.'s analysis. It highlights how a decision to stop breastfeeding in the current UK context may lead to experiencing a lack of support from healthcare professionals. We argue that a family-centred approach to infant feeding should acknowledge the benefits and costs of all infant feeding methods and enable all families to be fully informed and supported in feeding their babies.}, } @article {pmid32181808, year = {2020}, author = {Tello, N and Jaafari, N and Chatard, A}, title = {Effects of Evaluative Conditioning on Implicit Evaluation of Alcohol and Drinking Behaviors: A Direct Replication.}, journal = {Alcohol and alcoholism (Oxford, Oxfordshire)}, volume = {55}, number = {3}, pages = {299-303}, doi = {10.1093/alcalc/agaa009}, pmid = {32181808}, issn = {1464-3502}, mesh = {Alcohol Drinking/psychology/*therapy ; Alcoholic Beverages ; *Conditioning, Classical ; *Drinking Behavior ; Female ; Humans ; Male ; Reproducibility of Results ; Students/psychology ; Young Adult ; }, abstract = {AIMS: Recent research suggests that evaluative conditioning (EC) can change implicit evaluations of alcohol and reduce drinking behaviors among college students (Houben et al., 2010a). This research has been conceptually replicated in two previous studies. To date, however, no direct and independent replication of the original study has been performed. In this paper, we report a high-powered direct replication of Houben et al.'s (2010a) study.

METHOD: About 168 French college students took part in this preregistered study. Drinking behavior was assessed before and 2 weeks after the intervention. The intervention consisted of 120 trials of words related to alcoholic beverages or soft drinks paired with neutral, positive or negative pictures. The two conditions were factually equivalent and differed only in the repeated pairing between alcohol-related words and negative pictures; in the EC condition, but not in the control condition, alcohol-related words were systematically paired with negative pictures.

RESULTS: EC did not change participants' implicit evaluations of alcohol and drinking behaviors. However, EC reduced drinking behaviors among hazardous drinkers. Yet, further non-preregistered Bayesian analysis did not provide much support for this hypothesis.

CONCLUSION: This high-powered preregistered direct replication of Houben et al.'s (2010a) study suggests that the original effects are more fragile than initially thought. The effect of EC on drinking behaviors may be restricted to heavy drinkers, and we found no evidence that this effect is mediated by a change in implicit attitudes. It is necessary to perform further studies to test the original effects in clinical populations.}, } @article {pmid32176402, year = {2020}, author = {Fertitta, L and Hotz, C and Sbidian, E}, title = {Response to Marasca et al.'s letter about place of ultrasound in the evaluation of HS lesions.}, journal = {Journal of the European Academy of Dermatology and Venereology : JEADV}, volume = {34}, number = {8}, pages = {e412-e413}, doi = {10.1111/jdv.16359}, pmid = {32176402}, issn = {1468-3083}, mesh = {*Hidradenitis Suppurativa ; Humans ; Ultrasonography ; }, } @article {pmid32174808, year = {2020}, author = {Zheng, KY and Dai, GY and Lan, Y and Wang, XQ}, title = {Trends of Repetitive Transcranial Magnetic Stimulation From 2009 to 2018: A Bibliometric Analysis.}, journal = {Frontiers in neuroscience}, volume = {14}, number = {}, pages = {106}, pmid = {32174808}, issn = {1662-4548}, abstract = {Repetitive transcranial magnetic stimulation (rTMS) technology, which is amongst the most used non-invasive brain stimulation techniques currently available, has developed rapidly from 2009 to 2018. However, reports on the trends of rTMS using bibliometric analysis are rare. The goal of the present bibliometric analysis is to analyze and visualize the trends of rTMS, including general (publication patterns) and emerging trends (research frontiers), over the last 10 years by using the visual analytic tool CiteSpace V. Publications related to rTMS from 2009 to 2018 were retrieved from the Web of Science (WoS) database, including 2,986 peer-reviewed articles/reviews. Active authors, journals, institutions, and countries were identified by WoS and visualized by CiteSpace V, which could also detect burst changes to identify emerging trends. GraphPad Prism 8 was used to analyze the time trend of annual publication outputs. The USA ranked first in this field. Pascual-Leone A (author A), Fitzgerald PB (author B), George MS (author C), Lefaucheur JP (author D), and Fregni F (author E) made great contributions to this field of study. The most prolific institution to publish rTMS-related publications in the last decade was the University of Toronto. The journal Brain Stimulation published most papers. Lefaucheur et al.'s paper in 2014, and the keyword "sham controlled trial" showed the strongest citation bursts by the end of 2018, which indicates increased attention to the underlying work, thereby indicating the research frontiers. This study reveals the publication patterns and emerging trends of rTMS based on the records published from 2009 to 2018. The insights obtained have reference values for the future research and application of rTMS.}, } @article {pmid32163189, year = {2020}, author = {Martínez, A and Anduro, I and Bojorquez, I}, title = {The biohabitus of scarcity: bio-social dispositions and the "obesity epidemic" in Mexico.}, journal = {Sociology of health & illness}, volume = {42}, number = {5}, pages = {1095-1107}, doi = {10.1111/1467-9566.13080}, pmid = {32163189}, issn = {1467-9566}, mesh = {Body Mass Index ; *Epidemics ; Food ; Humans ; Mexico/epidemiology ; *Obesity/epidemiology ; }, abstract = {In this article, we explore the potential of Warin et al.'s concept of biohabitus (a set of embodied biological and social dispositions) as a conceptual tool for the understanding of mechanisms behind the "obesity epidemic." Elaborating on this concept, we argue that a context of food scarcity gives rise to a biohabitus geared to energy-saving, expressed in both biological (the thrifty genotype/phenotype hypotheses) and symbolic dispositions (Bourdieu's "taste of necessity"), and the interaction between this type of biohabitus and changes in the food-related environment results in increased body mass index. We exemplify the use of this framework by applying it to the case of Mexico, a middle-income Latin American country with one of the highest prevalences of obesity worldwide. The example shows how the concept of biohabitus can help researchers move beyond disciplinary explanations, towards a more complex understanding of the conjunction of social and biological processes that result in differential patterns of health and disease.}, } @article {pmid32156812, year = {2020}, author = {Hird, SM}, title = {Context Is Key: Comparative Biology Illuminates the Vertebrate Microbiome.}, journal = {mBio}, volume = {11}, number = {2}, pages = {}, pmid = {32156812}, issn = {2150-7511}, mesh = {Animals ; Birds ; *Chiroptera ; *Gastrointestinal Microbiome ; *Microbiota ; Vertebrates ; }, abstract = {Microbes affect vertebrates on timescales from daily to evolutionary, and the cumulative effect of these interactions is immense. However, how microbiomes compare across (host) species is poorly understood, as most studies focus on relatively few species. A recent mBio article by S. J. Song, J. G. Sanders, F. Delsuc, J. Metcalf, et al. (mBio 11:e02901-19, 2019, https://doi.org/10.1128/mBio.02901-19) expands our collective understanding of the vertebrate microbiome by analyzing ∼900 species. They demonstrate that patterns within mammals contrast with those within birds. Their results suggest many hypotheses about the role of host ecology and evolution on microbiome variation. Bats, the only volant mammals, appear to contradict many of the general mammal microbiome trends, in some ways resembling birds. What role has powered flight, and the evolution thereof, played in microbiome structure and function? Comparative methods, mechanistic hypotheses, and theory will elucidate this exciting question (and others) that we can ask using Song, Sanders et al.'s data and results.}, } @article {pmid32156182, year = {2020}, author = {Van der Cruyssen, I and D'hondt, J and Meijer, E and Verschuere, B}, title = {Does Honesty Require Time? Two Preregistered Direct Replications of Experiment 2 of Shalvi, Eldar, and Bereby-Meyer (2012).}, journal = {Psychological science}, volume = {31}, number = {4}, pages = {460-467}, pmid = {32156182}, issn = {1467-9280}, mesh = {Adult ; Bayes Theorem ; *Deception ; Decision Making/*physiology ; Female ; Humans ; Male ; *Morals ; *Reward ; Time Factors ; Young Adult ; }, abstract = {Shalvi, Eldar, and Bereby-Meyer (2012) found across two studies (N = 72 for each) that time pressure increased cheating. These findings suggest that dishonesty comes naturally, whereas honesty requires overcoming the initial tendency to cheat. Although the study's results were statistically significant, a Bayesian reanalysis indicates that they had low evidential strength. In a direct replication attempt of Shalvi et al.'s Experiment 2, we found that time pressure did not increase cheating, N = 428, point biserial correlation (rpb) = .05, Bayes factor (BF)01 = 16.06. One important deviation from the original procedure, however, was the use of mass testing. In a second direct replication with small groups of participants, we found that time pressure also did not increase cheating, N = 297, rpb = .03, BF01 = 9.59. These findings indicate that the original study may have overestimated the true effect of time pressure on cheating and the generality of the effect beyond the original context.}, } @article {pmid32156080, year = {2020}, author = {Xiao, Y and Zhang, T and Gu, X and Lee, J and Wang, H}, title = {The Roles of Individual and Psychosocial Factors in Predicting Quality of Life Among Working Women in Shanghai.}, journal = {International journal of environmental research and public health}, volume = {17}, number = {5}, pages = {}, pmid = {32156080}, issn = {1660-4601}, mesh = {Burnout, Professional ; China ; Cross-Sectional Studies ; Female ; Humans ; Middle Aged ; *Quality of Life ; *Stress, Psychological ; Surveys and Questionnaires ; *Women, Working ; }, abstract = {Working women are at a high risk of suffering from occupational stress and burnout, which can result in reducing Quality of Life (QoL). Guided by the QoL construct and Luban et al.'s conceptual framework, this study aimed to (a) investigate the roles of individual factors (i.e., age) and psychosocial factors (i.e., occupational stress, burnout) on QoL among working women, and (b) examine the age differences among study variables (young versus middle-aged groups). Participants were 375 working women (Mage = 42.06) recruited in Shanghai, China. They completed previously validated questionnaires assessing their occupational stress, burnout (emotional exhaustion, cynicism, and reduced professional efficacy), and QoL (physical health, psychological health, social relationship, and living environment). Confirmatory factor analysis, Pearson product-moment correlation, hierarchical regressions, and factorial multivariate analyses of variance (MANOVA) were used to examine the relationships and differences between occupational stress, burnout, and QoL among working women. Correlation and regression analyses indicated that occupational stress and burnout were significantly associated with QoL among these participants. Two one-factor MANOVAs demonstrated that young-aged working women had higher occupational stress and burnout, but lower levels of QoL than middle-aged women. These results suggest that adopting specific coping strategies to reduce or prevent occupational stress and burnout are needed to improve QoL among working women.}, } @article {pmid32152668, year = {2021}, author = {Macnamara, BN and Hambrick, DZ}, title = {Toward a cumulative science of expertise: commentary on Moxley, Ericsson, and Tuffiash (2017).}, journal = {Psychological research}, volume = {85}, number = {3}, pages = {1108-1113}, pmid = {32152668}, issn = {1430-2772}, mesh = {Female ; Humans ; Male ; *Practice, Psychological ; *Professional Competence ; }, abstract = {In a recent Psychological Research article, Moxley, Ericsson, and Tuffiash (2017) report two studies of SCRABBLE expertise. The results revealed that the average SCRABBLE rating was higher for males than for females. Moreover, correlational and structural equation analyses revealed that activities that the authors refer to as "purposeful practice" accounted for a substantial amount of the variance in SCRABBLE ratings. The authors generalize their findings concerning SCRABBLE to STEM careers. We believe this generalization is unjustified, as is their argument that SCRABBLE can be used to understand the gender gap in STEM fields. Moreover, the authors' conclusions are undermined by inconsistencies and contradictions in their arguments. We discuss these problems with Moxley et al.'s article in terms of their impact on the cumulative science of expertise.}, } @article {pmid32141095, year = {2020}, author = {Grover, LK and Kaur, A}, title = {Corrected estimator of sensitive population proportion using unknown repeated trials in the unrelated question randomized response model.}, journal = {Biometrical journal. Biometrische Zeitschrift}, volume = {62}, number = {5}, pages = {1337-1342}, doi = {10.1002/bimj.201900334}, pmid = {32141095}, issn = {1521-4036}, mesh = {Biometry ; Humans ; *Models, Statistical ; *Vulnerable Populations ; }, abstract = {In this paper, we have pointed out a major mistake in the research paper of Singh and Mathur [(2004). Unknown repeated trials in the unrelated question randomized response model, Biometrical Journal, 46:375-378]. We have corrected this mistake and proposed the corresponding corrected estimator of sensitive population proportion. Furthermore, we have obtained the variance of our proposed estimator. Likewise, Singh and Mathur, we have also compared the variance of our proposed estimator with that of the Greenberg et al.'s estimator theoretically as well as numerically.}, } @article {pmid32130506, year = {2021}, author = {Lien, MC and Allen, PA and Ruthruff, E}, title = {Case mixing impedes early lexical access: converging evidence from the masked priming paradigm.}, journal = {Psychological research}, volume = {85}, number = {3}, pages = {1317-1337}, pmid = {32130506}, issn = {1430-2772}, mesh = {Adolescent ; Adult ; Cognition/*physiology ; Female ; Humans ; Male ; Motor Activity/*physiology ; Oregon ; Pattern Recognition, Visual/*physiology ; *Reading ; Young Adult ; }, abstract = {When letters are presented in mixed case (e.g., "PlAnE), word recognition is slowed. This case-mixing effect has been used to argue that early stages of word recognition operate holistically (on the entire visual word form) rather than merely letter-by-letter. Contrary to this holistic view, however, a masked priming study (Perea, Vergara-Martínez, & Gomez, Cognition 142:39-43, 2015) with Spanish words argued that case mixing has no effect on early stages of visual word recognition. Their participants made lexical decisions on an uppercase target (e.g., "PLANE") preceded by an identical prime (e.g., "plane") or an unrelated prime (e.g., "music"), presented in lowercase or mixed case. Because priming effects (unrelated-identical) were unaffected by case mixing, they concluded that case mixing does not impede early lexical access. We examined whether this finding applies to English words, while also including lowercase targets to prevent a strong bias against holistic word recognition. We found larger priming effects from lowercase primes than mixed-case primes regardless of target case (lowercase vs. uppercase) and whether target case was varied within blocks (Experiment 1) or between blocks (Experiment 2). Contrary to Perea et al.'s findings for Spanish, our results suggest an early locus for the case-mixing effect, consistent with the holistic view of word recognition.}, } @article {pmid32112836, year = {2020}, author = {Fan, H and Wang, Q and Li, K}, title = {Remarks on "Comments on 'Effect of hydrolysed cellulose nanowhiskers on properties of montmorillonite/polylactic acid nanocomposites' By Reza Arjmandi et al." By Djalal Trache.}, journal = {International journal of biological macromolecules}, volume = {153}, number = {}, pages = {676-679}, doi = {10.1016/j.ijbiomac.2020.02.301}, pmid = {32112836}, issn = {1879-0003}, mesh = {Bentonite ; *Cellulose ; *Nanocomposites ; Polyesters ; }, abstract = {The Coats-Redfern method is commonly used to calculate the activation energy of the thermal degradation from a single non-isothermal thermogravimetric curve since its first proposal in 1964. This paper represents the accurate expressions, sound derivation process and proper usage of the Coats-Redfern equations, based on the critique into the Coats-Redfern's original article, Djalal Trache's incorrect comments on Reza Arjmandi et al.'s article, and the flaw in Reza Arjmandi et al.'s work per se.}, } @article {pmid32110432, year = {2020}, author = {Cox, J and Linthwaite, B and Engler, K and Lessard, D and Lebouché, B and Kronfli, N}, title = {A type II implementation-effectiveness hybrid quasi-experimental pilot study of a clinical intervention to re-engage people living with HIV into care, 'Lost & Found': an implementation science protocol.}, journal = {Pilot and feasibility studies}, volume = {6}, number = {}, pages = {29}, pmid = {32110432}, issn = {2055-5784}, abstract = {BACKGROUND: At the McGill University Health Centre (MUHC), 10% of patients living with HIV do not return for care annually. Currently, no formal system exists to re-engage out-of-care (OOC) patients. Lost & Found, developed using an implementation science approach, is an intervention to re-engage OOC patients. It is based on existing evidence-based interventions and will be adapted for use by nurses at the MUHC. The aims of this study are to simultaneously assess both implementation and effectiveness of Lost & Found in order to determine the viability of a future multisite stepped-wedge cluster randomised trial.

METHODS: Lost & Found consists of two core elements: identifying and contacting OOC patients. Based on formative work involving MUHC nurses, and the use of a combined implementation framework (enhanced Replicating Effective Programs, Tailored Implementation for Chronic Diseases, and Proctor et al.'s implementation outcomes), we will adapt the intervention to our clinic. Adaptations include the creation of an OOC risk prediction tool, an automated real-time OOC list, and prioritization of high-risk OOC patients for re-engagement. Delivery and ongoing adaptation of the intervention will follow a three-pronged implementation strategy consisting of (1) promoting adaptability; (2) planning, engaging, executing, evaluating, and reflecting cycles; and (3) internal facilitation. This 15-month quasi-experimental pilot study adopts a type II implementation-effectiveness hybrid design. To evaluate implementation, a convergent parallel mixed-methods approach will guide the mixing of qualitative and quantitative data at time points throughout the study. In addition, descriptive and pre-post analyses, for each of the implementation and sustainability phases, will inform evaluations of the cumulative effectiveness and sustainability of the Lost & Found intervention.

DISCUSSION: This study will provide preliminary evidence for (1) the utility of our chosen implementation strategies and (2) the effectiveness of the intervention. Ultimately, this information may be used to inform future re-engagement efforts using implementation science in other HIV care centres. In addition, the procedures and measurement tools developed for this study will be foundational to the development of a multi-site, randomised stepped wedge study that would provide more robust evidence in support of the Lost & Found intervention.}, } @article {pmid32106288, year = {2020}, author = {Isler, J and Sawadogo, NH and Harling, G and Bärnighausen, T and Adam, M and Sié, A and McMahon, SA}, title = {'If he sees it with his own eyes, he will understand': how gender informed the content and delivery of a maternal nutrition intervention in Burkina Faso.}, journal = {Health policy and planning}, volume = {35}, number = {5}, pages = {536-545}, pmid = {32106288}, issn = {1460-2237}, support = {/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Adult ; Breast Feeding ; Burkina Faso ; Child ; Child Nutrition Disorders/prevention & control ; Community Health Workers/psychology ; Female ; Focus Groups ; *Gender Role ; Humans ; Male ; Marriage/*psychology ; Maternal Nutritional Physiological Phenomena ; Mothers ; Pregnancy ; *Prenatal Nutritional Physiological Phenomena ; Qualitative Research ; }, abstract = {A growing body of literature urges policymakers, practitioners and scientists to consider gender in the design and evaluation of health interventions. We report findings from formative research to develop and refine an mHealth maternal nutrition intervention in Nouna, Burkina Faso, one of the world's most resource-poor settings. Gender was not an initial research focus, but emerged as highly salient during data collection, and thus guided lines of inquiry as the study progressed. We collected data in two stages, first using focus group discussions (FGD; n = 8) and later using FGDs (n = 2), interviews (n = 30) and observations of intervention delivery (n = 30). Respondents included pregnant women, breastfeeding mothers and Close-to-Community (CTC) providers, who execute preventative and curative tasks at the community level. We applied Morgan et al.'s gender framework to examine intervention content (what a gender-sensitive nutrition programme should entail) and delivery (how a gender-sensitive programme should be administered). Mothers emphasized that although they are often the focus of nutrition interventions, they are not empowered to make nutrition-based decisions that incur costs. They do, however, wield some control over nutrition-related tasks such as farming and cooking. Mothers described how difficult it is to consider only one's own children during meal preparation (which is communal), and all respondents described how nutrition-related requests can spark marital strife. Many respondents agreed that involving men in nutrition interventions is vital, despite men's perceived disinterest. CTC providers and others described how social norms and gender roles underpin perceptions of CTC providers and dictate with whom they can speak within homes. Mothers often prefer female CTC providers, but these health workers require spousal permission to work and need to balance professional and domestic demands. We recommend involving male partners in maternal nutrition interventions and engaging and supporting a broader cadre of female CTC providers in Burkina Faso.}, } @article {pmid32096437, year = {2020}, author = {Kyriacou, CP and Dowse, HB and Zhang, L and Green, EW}, title = {A Computational Error and Restricted Use of Time-series Analyses Underlie the Failure to Replicate period-Dependent Song Rhythms in Drosophila.}, journal = {Journal of biological rhythms}, volume = {35}, number = {3}, pages = {235-245}, doi = {10.1177/0748730420901929}, pmid = {32096437}, issn = {1552-4531}, support = {BB/K009702/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Animals ; *Circadian Rhythm ; Courtship ; Drosophila melanogaster/*genetics/*physiology ; Genotype ; Models, Theoretical ; Music ; Mutation ; Period Circadian Proteins/genetics ; Scientific Experimental Error ; *Sexual Behavior, Animal ; }, abstract = {From 1980 to 1991, Kyriacou, Hall, and collaborators (K&H) reported that the Drosophila melanogaster courtship song has a 1-min cycle in the length of mean interpulse intervals (IPIs) that is modulated by circadian rhythm period mutations. In 2014, Stern failed to replicate these results using a fully automated method for detecting song pulses. Manual annotation of Stern's song records exposed a ~50% error rate in detection of IPIs, but the corrected data revealed period-dependent IPI cycles using a variety of statistical methods. In 2017, Stern et al. dismissed the sine/cosine method originally used by K&H to detect significant cycles, claiming that randomized songs showed as many significant values as real data using cosinor analysis. We first identify a simple mathematical error in Stern et al.'s cosinor implementation that invalidates their critique of the method. Stern et al. also concluded that although the manually corrected wild-type and per[L] mutant songs show similar periods to those observed by K&H, each song is usually not significantly rhythmic by the Lomb-Scargle (L-S) periodogram, so any genotypic effect simply reflects "noise." Here, we observe that L-S is extremely conservative compared with 3 other time-series analyses in assessing the significance of rhythmicity, both for conventional locomotor activity data collected in equally spaced time bins and for unequally spaced song records. Using randomization of locomotor and song data to generate confidence limits for L-S instead of the theoretically derived values, we find that L-S is now consistent with the other methods in determining significant rhythmicity in locomotor and song records and that it confirms period-dependent song cycles. We conclude that Stern and colleagues' failure to identify song cycles stems from the limitations of automated methods in accurately reflecting song parameters, combined with the use of an overly stringent method to discriminate rhythmicity in courtship songs.}, } @article {pmid32078554, year = {2020}, author = {Nakanishi, M and Xu, M and Wang, Y and Chiang, KJ and Han, J and Jung, TP}, title = {Questionable Classification Accuracy Reported in "Designing a Sum of Squared Correlations Framework for Enhancing SSVEP-Based BCIs".}, journal = {IEEE transactions on neural systems and rehabilitation engineering : a publication of the IEEE Engineering in Medicine and Biology Society}, volume = {28}, number = {4}, pages = {1042-1043}, doi = {10.1109/TNSRE.2020.2974272}, pmid = {32078554}, issn = {1558-0210}, support = {R21 EY025056/EY/NEI NIH HHS/United States ; }, mesh = {*Brain-Computer Interfaces ; Electroencephalography ; *Evoked Potentials, Visual ; Neurologic Examination ; }, abstract = {This commentary presents a replication study to verify the effectiveness of a sum of squared correlations (SSCOR)-based steady-state visual evoked potentials (SSVEPs) decoding method proposed by Kumar et al.. We implemented the SSCOR-based method in accordance with their descriptions and estimated its classification accuracy using a benchmark SSVEP dataset with cross validation. Our results showed significantly lower classification accuracy compared with the ones reported in Kumar et al.'s study. We further investigated the sources of performance discrepancy by simulating data leakage between training and test datasets. The classification performance of the simulation was remarkably similar to those reported by Kumar et al.. We, therefore, question the validity of evaluation and conclusions drawn in Kumar et al.'s study.}, } @article {pmid32077921, year = {2020}, author = {Tsai, MH}, title = {Response to Chen Guan et al.'s comments on our published article 'miR-338-5p inhibits cell proliferation, colony formation, migration, and cisplatin resistance in esophageal squamous cancer cells by targeting FERMT2'.}, journal = {Carcinogenesis}, volume = {41}, number = {2}, pages = {245}, doi = {10.1093/carcin/bgz090}, pmid = {32077921}, issn = {1460-2180}, mesh = {Cell Proliferation ; Cisplatin ; *Esophageal Neoplasms ; *Esophageal Squamous Cell Carcinoma ; Humans ; *MicroRNAs ; }, } @article {pmid32077726, year = {2020}, author = {Valiente, C and Swanson, J and DeLay, D and Fraser, AM and Parker, JH}, title = {Emotion-related socialization in the classroom: Considering the roles of teachers, peers, and the classroom context.}, journal = {Developmental psychology}, volume = {56}, number = {3}, pages = {578-594}, pmid = {32077726}, issn = {1939-0599}, support = {R01 HD068522/HD/NICHD NIH HHS/United States ; //Institute of Education Sciences/ ; //National Institutes of Health; Eunice Kennedy Shriver National Institute of Child Health and Human Development/ ; }, mesh = {*Academic Success ; Child ; *Emotions ; Humans ; *Peer Group ; *School Teachers ; *Schools ; *Self-Control ; *Social Adjustment ; *Socialization ; }, abstract = {The goal of this study was to apply aspects of the heuristic model advanced by Eisenberg, Cumberland, and Spinrad (1998) to the study of socialization that takes place in preschool and elementary school classrooms. Investigating socialization in this context is important given the number of hours students spend in school, the emotional nature of social interactions that take place involving teachers and students, and the emotions students often experience in the context of academic work. Guided by Eisenberg, Cumberland, et al.'s (1998) call to consider complex socialization pathways, we focus our discussion on ways teachers, peers, and the classroom context can shape students' emotion-related outcomes (e.g., self-regulation, adjustment) and academic-related outcomes (e.g., school engagement, achievement) indirectly and differentially (e.g., as a function of student or classroom characteristics). Our illustrative review of the intervention literature demonstrates that the proposed classroom-based socialization processes have clear applied implications, and efforts to improve socialization in the classroom can promote students' emotional and academic competence. We conclude our discussion by outlining areas that require additional study. (PsycINFO Database Record (c) 2020 APA, all rights reserved).}, } @article {pmid32077720, year = {2020}, author = {Chen, X and McCormick, EM and Ravindran, N and McElwain, NL and Telzer, EH}, title = {Maternal emotion socialization in early childhood predicts adolescents' amygdala-vmPFC functional connectivity to emotion faces.}, journal = {Developmental psychology}, volume = {56}, number = {3}, pages = {503-515}, doi = {10.1037/dev0000852}, pmid = {32077720}, issn = {1939-0599}, support = {//National Science Foundation/ ; //US Department of Agriculture; National Institute of Food and Agriculture/ ; //University of Illinois Research Board/ ; //Jacobs Foundation/ ; }, mesh = {Adolescent ; Amygdala/diagnostic imaging/*physiology ; Child ; Child Development/*physiology ; Child, Preschool ; *Connectome ; Emotions/*physiology ; *Facial Expression ; Facial Recognition/*physiology ; Female ; Humans ; Longitudinal Studies ; Magnetic Resonance Imaging ; Male ; Maternal Behavior/*physiology ; Prefrontal Cortex/diagnostic imaging/*physiology ; *Socialization ; }, abstract = {Guided by Eisenberg, Cumberland, and Spinrad's (1998) conceptual framework, we examined multiple components of maternal emotion socialization (i.e., reactions to children's negative emotion, emotion talk, emotional expressiveness) at 33 months of age as predictors of adolescents' amygdala-vmPFC connectivity and amygdala activation when labeling and passively observing angry and happy faces. For angry faces, more positive maternal emotion socialization behaviors predicted (a) less positive amygdala-vmPFC connectivity, which may reflect more mature vmPFC downregulation of the amygdala activation underlying implicit emotion regulation, and (b) more amygdala activation, which may reflect higher sensitivity to others' emotional cues. Associations between negative emotion socialization behaviors and neural responses to angry faces were nonsignificant, and findings for the models predicting neural responses to happy faces showed a less consistent pattern. By expanding Eisenberg et al.'s (1998) framework to consider neural processing of negative emotions, the current findings point toward the potential long-term implications of positive emotion socialization experiences during early childhood for optimal functioning of the amygdala-vmPFC circuitry during adolescence. (PsycINFO Database Record (c) 2020 APA, all rights reserved).}, } @article {pmid32077647, year = {2019}, author = {Buttigieg, SC and Azzopardi, EA and Cassar, V}, title = {The Mediating Role of Burnout in the Relationship between Perceived Patient-safe, Friendly Working Environment and Perceived Unsafe Performance in an Obstetric Unit.}, journal = {Advances in health care management}, volume = {18}, number = {}, pages = {}, doi = {10.1108/S1474-823120190000018005}, pmid = {32077647}, issn = {1474-8231}, mesh = {*Burnout, Professional ; Cross-Sectional Studies ; Female ; Humans ; Infant, Newborn ; Malta ; *Obstetrics ; *Occupational Stress ; Pregnancy ; Workplace ; }, abstract = {Medical errors in obstetric departments are commonly reported and may involve both mother and neonate. The complexity of obstetric care, the interactions between various disciplines, and the inherent limitations of human performance make it critically important for these departments to provide patient-safe and friendly working environments that are open to learning and participative safety. Obstetric care involves stressful work, and health care professionals are prone to develop burnout, this being associated with unsafe practices and lower probability for reporting safety concerns. This study aims to test the mediating role of burnout in the relationship of patient-safe and friendly working environment with unsafe performance. The full population of professionals working in an obstetrics department in Malta was invited to participate in a cross-sectional study, with 73.6% (n = 184) of its members responding. The research tool was adapted from the Sexton et al.'s Safety Attitudes Questionnaire - Labor and Delivery version and surveyed participants on their working environment, burnout, and perceived unsafe performance. Analysis was done using Structural Equation Modeling. Results supported the relationship between the lack of a perceived patient-safe and friendly working environment and unsafe performance that is mediated by burnout. Creating a working environment that ensures patient safety practices, that allows communication, and is open to learning may protect employees from burnout. In so doing, they are more likely to perceive that they are practicing safely. This study contributes to patient safety literature by relating working environment, burnout, and perceived unsafe practice with the intention of raising awareness of health managers' roles in ensuring optimal clinical working environment for health care employees.}, } @article {pmid32076977, year = {2020}, author = {Pierce, C}, title = {Capsule Commentary on Weber et al.'s Development and Establishment of Initial Validity Evidence for a Novel Tool for Assessing Trainee Admission Notes.}, journal = {Journal of general internal medicine}, volume = {35}, number = {4}, pages = {1360}, pmid = {32076977}, issn = {1525-1497}, mesh = {*Hospitalization ; Humans ; }, } @article {pmid32074127, year = {2020}, author = {Zogmaister, C and Durante, F and Mari, S and Crippa, F and Volpato, C}, title = {Measuring objectification through the Body Inversion Paradigm: Methodological issues.}, journal = {PloS one}, volume = {15}, number = {2}, pages = {e0229161}, pmid = {32074127}, issn = {1932-6203}, mesh = {Adult ; Female ; Humans ; Male ; *Self Concept ; Sexism/psychology ; Sexual Behavior/psychology ; Young Adult ; }, abstract = {Objectification occurs when a person is perceived and/or treated like an object. With the present work, we overview the available measures of objectification and present a series of studies aimed at investigating the validity of the task of inverted body recognition proposed by Bernard and colleagues (2012), which might potentially be a useful cognitive measure of objectification. We conducted three studies. Study 1 (N = 101) is a direct replication of Bernard et al.'s study: participants were presented with the same photos of sexualized male and female targets used in the original research. Study 2a (N = 100) is a conceptual replication: we used different images of scantily dressed male and female models. Finally, in Study 2b (N = 100), we investigated a boundary condition by presenting to participants photos of the same models as in Study 2a, but fully dressed and non-sexualized. Using mixed-effects models for completely-crossed classified data structures, we investigated the relationship between the inversion effect and the stimulus' asymmetry, sexualization and attractiveness, and the perceivers' self-objectification, sexism, and automatic woman-human association. Study 1 replicated the original results, showing a stronger inversion effect for male photos. However, no difference between male and female stimuli emerged in either Study 2a or 2b. Moreover, the impact of the other variables on the inversion effect was highly unstable across the studies. These aspects together indicate that the inversion effect depends on the specific set of stimuli and limits the generalizability of results collected using this method.}, } @article {pmid32073287, year = {2020}, author = {Tumanova, V and Woods, C and Razza, R}, title = {The Role of Behavioral Inhibition for Conversational Speech and Language Characteristics of Preschool-Age Children Who Stutter.}, journal = {American journal of speech-language pathology}, volume = {29}, number = {2}, pages = {638-651}, doi = {10.1044/2019_AJSLP-19-00026}, pmid = {32073287}, issn = {1558-9110}, mesh = {Child ; Child, Preschool ; Communication ; Humans ; Inhibition, Psychological ; Speech ; Speech Production Measurement ; *Stuttering/diagnosis/therapy ; }, abstract = {Purpose The purpose of this study was to investigate whether preschool-age children who stutter (CWS) were more likely to exhibit a temperamental trait of behavioral inhibition (BI), a correlate of shyness, than children who do not stutter (CWNS) and whether this temperamental trait affected preschool-age children's speech fluency and language complexity during a conversation with an unfamiliar adult. Method Sixty-eight preschool-age children (31 CWS, 37 CWNS) participated. The degree of BI was assessed by measuring the latency to their sixth spontaneous comment and the number of all spontaneous comments during a conversation with an unfamiliar examiner (following Kagan et al.'s [1987] methodology). Parent report of shyness from the Children's Behavior Questionnaire served as an indirect measure of BI. Children's language complexity was assessed by measuring their mean length of utterance and the number of words spoken. For CWS, the frequency of stuttering and the negative impact of stuttering were also assessed. Results First, we found no between-group differences in the degree of BI across the behavioral observation measures. However, CWS were rated shyer by parents than CWNS. Second, for CWS only, higher BI was associated with less complex utterances and fewer words spoken. Third, for CWS, higher BI was associated with fewer stuttered disfluencies produced. Conclusions This study provides empirical evidence that BI to the unfamiliar may have salience for childhood stuttering as it affected the quantity and quality of language spoken with an unfamiliar adult. Clinical implications of high BI for the assessment and treatment of preschool-age stuttering are discussed.}, } @article {pmid32060701, year = {2021}, author = {Maquestiaux, F and Arexis, M and Chauvel, G and Ladoy, J and Boyer, P and Mazerolle, M}, title = {Ebbinghaus visual illusion: no robust influence on novice golf-putting performance.}, journal = {Psychological research}, volume = {85}, number = {3}, pages = {1156-1166}, pmid = {32060701}, issn = {1430-2772}, mesh = {Adult ; Athletic Performance/*physiology/psychology ; Female ; France ; Golf/*physiology/*psychology ; Humans ; Illusions/*physiology/*psychology ; Male ; Size Perception/*physiology ; Students/psychology/statistics & numerical data ; Universities ; Visual Perception/*physiology ; Young Adult ; }, abstract = {Do visual illusions reliably improve sports performance? To address this issue, we used procedures inspired by Witt et al. (Psychol Sci 23:397-399, 2012) seminal study, which reported that putting on a miniature golf course was positively influenced by an increase in apparent hole size induced by the Ebbinghaus visual illusion. Because Witt et al.'s motor task-putting golf balls toward a hole from the distance of 3.5 m-was impossible for participants who were novices in golf (Experiment 1a), we decided to shorten the putting distance (i.e., 2 m instead of 3.5 m) in Experiment 1b. Otherwise, this second experiment closely followed every other aspects of Witt et al.'s procedure (i.e., one small or one standard golf hole surrounded by a ring of small or large circles). However, this attempt to replicate Witt et al.'s findings failed: the Ebbinghaus illusion significantly influenced neither hole perception nor putting performance. In two subsequent experiments, we encouraged the emergence of the effect of the illusion by simultaneously presenting both versions of the illusion on the mat. This major adaptation successfully modified the perceived size of the hole but had no impact on putting performance (Experiment 2), even when the putting task was made easier by shortening the putting distance to only 1 m (Experiment 3). In the absence of detectable effects of the illusion on putting performance, we conclude that the effects of visual illusions on novice sports performance do not represent a robust phenomenon.}, } @article {pmid32057928, year = {2020}, author = {Park, J and Chun, KH}, title = {Identification of novel functions of the ROCK2-specific inhibitor KD025 by bioinformatics analysis.}, journal = {Gene}, volume = {737}, number = {}, pages = {144474}, doi = {10.1016/j.gene.2020.144474}, pmid = {32057928}, issn = {1879-0038}, mesh = {*Computational Biology ; Gene Expression ; Heterocyclic Compounds, 4 or More Rings/*pharmacology ; Humans ; Oligonucleotide Array Sequence Analysis ; Protein Kinase Inhibitors/*pharmacology ; rho-Associated Kinases/*antagonists & inhibitors ; }, abstract = {Rho-associated protein kinases (ROCKs) have various cellular functions, which include actin cytoskeleton remodeling and vesicular trafficking, and there are two major mammalian ROCK isotypes, namely, ROCK1 (ROKβ) and ROCK2 (ROKα). The ROCK2-specific inhibitor KD025 (SLx-2119) is currently undergoing phase II clinical trials, but its cellular functions have not been fully explored. In this study, we investigated the functions of KD025 at the genomics level by bioinformatics analysis using the GSE8686 microarray dataset from the NCBI GEO database, in three different primary human cell lines. An initial microarray analysis conducted by Boerma et al. focused on the effects of KD025 on cell adhesion and blood coagulation, but did not provide comprehensive information on the functions of KD025. Our analysis of differentially expressed genes (DEGs) showed ~70% coincidence with Boerma et al.'s findings, and newly identified that CCND1, CXCL2, NT5E, and SMOX were differentially expressed by KD025. However, due to low numbers of co-regulated DEGs, we were unable to extract the functions of KD025 with significance. To overcome this limitation, we used gene set enrichment analysis (GSEA) and the heatmap hierarchical clustering method. We confirmed KD025 regulated inflammation and adipogenesis pathways, as previously reported experimentally. In addition, we found KD025 has novel regulatory functions on various pathways, including oxidative phosphorylation, WNT signaling, angiogenesis, and KRAS signaling. Further studies are required to systematically characterize these newly identified functions of KD025.}, } @article {pmid32057787, year = {2020}, author = {Whyte, W and Lytsy, B}, title = {Criticisms of Teo et al.'s study of ultraclean air systems in operating theatres.}, journal = {The Journal of hospital infection}, volume = {105}, number = {2}, pages = {339-340}, doi = {10.1016/j.jhin.2020.02.001}, pmid = {32057787}, issn = {1532-2939}, mesh = {*Arthroplasty, Replacement, Knee ; Humans ; *Infections ; Operating Rooms ; Ventilation ; }, } @article {pmid32037443, year = {2021}, author = {Leigh, JP}, title = {Invited Commentary: Methods for Estimating Effects of Minimum Wages on Health.}, journal = {American journal of epidemiology}, volume = {190}, number = {1}, pages = {31-34}, doi = {10.1093/aje/kwaa019}, pmid = {32037443}, issn = {1476-6256}, mesh = {Adult ; Cross-Sectional Studies ; Employment ; Humans ; *Income ; Occupations ; *Salaries and Fringe Benefits ; }, abstract = {Economists have been researching effects of minimum wages on unemployment, poverty, income inequality, and educational attainment for over 60 years. Epidemiologists have only recently begun researching minimum wages even though unemployment through education are central topics within social epidemiology. Buszkiewicz et al. (Am J Epidemiol. 2021;190(1):21-30) offer a welcome addition to this nascent literature. A commanding advantage of Buszkiewicz et al.'s study over others is its distinction between a "likely affected" group comprised of workers with ≤12 years of schooling versus "not likely affected" groups with ≥13 years of schooling. But there are disadvantages, common to other studies. Buszkiewicz et al. use cross-sectional data; they include the self-employed as well as part-time and part-year workers in their treatment groups. Their definitions of affected groups based on education create samples with 75% or more of workers who earn significantly above minimum wages; definitions are not based on wages. Inclusion of workers not subject to (e.g., self-employed) or affected by minimum wages biases estimates toward the null. Finally, within any minimum wage data set, it is the state-not federal-increases that account for the lion's share of increases and that form the natural experiments; however, state increases can occur annually whereas the development of chronic diseases might take decades.}, } @article {pmid32035973, year = {2020}, author = {Rezaie-Keikhaie, K and Arbabshastan, ME and Rafiemanesh, H and Amirshahi, M and Ostadkelayeh, SM and Arbabisarjou, A}, title = {Systematic Review and Meta-Analysis of the Prevalence of the Maternity Blues in the Postpartum Period.}, journal = {Journal of obstetric, gynecologic, and neonatal nursing : JOGNN}, volume = {49}, number = {2}, pages = {127-136}, doi = {10.1016/j.jogn.2020.01.001}, pmid = {32035973}, issn = {1552-6909}, mesh = {Adolescent ; Adult ; Depression, Postpartum/*diagnosis/epidemiology ; Female ; Humans ; *Postpartum Period ; *Prevalence ; }, abstract = {OBJECTIVE: To determine the prevalence of maternity blues among women in the postpartum period.

DATA SOURCES: We conducted our systematic review and meta-analysis by searching the literature for relevant articles published in three international databases, PubMed, Web of Science, and Scopus, from date of inception through December 11, 2019, using the keywords prevalence, incidence, maternity blues, and baby blues.

STUDY SELECTION: From 336 articles initially screened, we included 26 articles in the systematic review and meta-analysis.

DATA EXTRACTION: Two independent reviewers used a standardized form to extract data from eligible articles. We evaluated the quality of individual studies and the overall evidence according to Hoy et al.'s risk of bias tool.

DATA SYNTHESIS: The prevalence of maternity blues in the 26 included studies was 13.7% to 76.0%. Based on the results of the random effects model, the prevalence of maternity blues in 5,667 women was 39.0% (95% confidence interval [32.3, 45.6]; I[2] = 96.6%). The prevalence of maternity blues among women in Africa was greatest at 49.6%.

CONCLUSION: Considering the great prevalence of maternity blues in women after childbirth, paying attention to the key symptoms of maternity blues and implementing educational programs for health care providers and mothers after childbirth are essential.}, } @article {pmid32031886, year = {2020}, author = {Jamieson, GA and Skraaning, G}, title = {The Harder They Fall? A Response to Wickens et al. (2019) Regarding the Generalizability of Lumberjack Predictions to Complex Work Settings.}, journal = {Human factors}, volume = {62}, number = {4}, pages = {535-539}, doi = {10.1177/0018720820904623}, pmid = {32031886}, issn = {1547-8181}, mesh = {*Automation ; *Awareness ; Forecasting ; Humans ; *Man-Machine Systems ; Task Performance and Analysis ; Workload ; *Workplace ; }, abstract = {OBJECTIVE: This article is a response to Wickens et al.'s (2019) critique of Jamieson and Skraaning (2019).

BACKGROUND: Wickens et al. (2019) offer a five-point critique of Jamieson and Skraaning (2019) that they claim tempers the strength of our conclusions.

APPROACH: We first correct a misrepresentation in the critique and then respond to each of the criticisms.

RESULTS: We preserve the strength of our skeptical conclusions about the applicability of the lumberjack model to complex work settings.

APPLICATIONS: We continue to caution system designers about the lack of evidence supporting the lumberjack model in the context of complex work systems.}, } @article {pmid32007790, year = {2020}, author = {Bagby, RM and Parker, JDA and Taylor, GJ}, title = {Twenty-five years with the 20-item Toronto Alexithymia Scale.}, journal = {Journal of psychosomatic research}, volume = {131}, number = {}, pages = {109940}, doi = {10.1016/j.jpsychores.2020.109940}, pmid = {32007790}, issn = {1879-1360}, abstract = {OBJECTIVE: Twenty-five years ago, this journal published two articles reporting the development and initial validation of the 20-Item Toronto Alexithymia Scale (TAS-20). Since then the literature on alexithymia has burgeoned with the vast majority of this research using the TAS-20, including multiple language translations of the scale.

METHOD: In this article we review the psychometric literature evaluating various aspects of the reliability and validity of the TAS-20 and examine some of the controversies surrounding the scale and the construct it assesses. We reflect on the ways in which the TAS-20 has advanced the measurement of the construct and theory of alexithymia. We also discuss recent developments and some future directions for the measurement of alexithymia.

RESULTS: Although not without some controversy, the preponderance of the accumulated evidence over a 25-year period supports various aspects of the reliability and validity of the TAS-20, including findings from confirmatory factor analytic and convergent and discriminant validity studies which are consistent with Nemiah et al.'s (Nemiah et al., 1976 [3]) and Taylor and colleagues (Taylor et al., 1997 [9]) theoretical formulations and definition of the alexithymia construct.

CONCLUSIONS: Based on the accumulated empirical evidence of 25 years, we conclude that the TAS-20 is a reliable and valid instrument and accurately reflects and measures the construct as it was originally defined by Nemiah et al. Nemiah et al. (1976) [3] as composed of deficits in affect awareness and expression and pensée opératoire (operational thinking). Clinicians and researchers can use the TAS-20 to confidently measure alexithymia, the roots of which have foundations in psychosomatic medicine.}, } @article {pmid32006720, year = {2020}, author = {Galica, J and Giroux, J and Francis, JA and Maheu, C}, title = {Coping with fear of cancer recurrence among ovarian cancer survivors living in small urban and rural settings: A qualitative descriptive study.}, journal = {European journal of oncology nursing : the official journal of European Oncology Nursing Society}, volume = {44}, number = {}, pages = {101705}, doi = {10.1016/j.ejon.2019.101705}, pmid = {32006720}, issn = {1532-2122}, mesh = {Adaptation, Psychological ; Aged ; Cancer Survivors/*psychology ; Fear/*psychology ; Female ; Humans ; Middle Aged ; Neoplasm Recurrence, Local/*psychology ; Ontario ; Ovarian Neoplasms/*psychology ; Phobic Disorders/*psychology ; Qualitative Research ; Rural Population/statistics & numerical data ; Survivors/psychology ; Urban Population/statistics & numerical data ; }, abstract = {PURPOSE: Fear of cancer recurrence (FCR) is a paramount concern among ovarian cancer survivors. Evidence shows that cancer survivors living in regional or rural areas have higher psychological morbidity; however, no known studies have explored how ovarian cancer survivors living in small urban and rural areas cope with FCR.

METHODS: In this qualitative descriptive study, a semi-structured questioning process was developed in accordance with Carver et al.'s conceptualization of coping. Focus groups or 1:1 telephone interviews were used to collect data from a convenience sample of ovarian cancer survivors. Participants completed a demographic form and the Fear of Cancer Recurrence Inventory, and clinical information was extracted from hospital charts.

RESULTS: The average age of participants (n = 15) was 62.8 years (Range 51-76 years) and the average time since diagnosis was 2.7 years (Range 1-19 years). Most women had elevated levels of FCR. Five themes for coping were expressed by all women: 1) health care provider support; 2) knowing, trusting, and prioritizing self; 3) finding what works; 4) uniqueness and belonging; and 5) redirecting thoughts and actions. One additional theme was expressed by most women (n = 11): 6) preparing for the future.

CONCLUSION: Fear of cancer recurrence was a concern for most ovarian cancer survivors who used a variety of ways to cope. Results can be used to guide nurses' discussions with post-treatment ovarian cancer survivors or be used to inform refinement and development of resources to assist ovarian cancer survivors living in small urban and rural settings to cope with FCR.}, } @article {pmid32005331, year = {2020}, author = {Seah, THS and Aurora, P and Coifman, KG}, title = {Emotion Differentiation as a Protective Factor Against the Behavioral Consequences of Rumination: A Conceptual Replication and Extension in the Context of Social Anxiety.}, journal = {Behavior therapy}, volume = {51}, number = {1}, pages = {135-148}, doi = {10.1016/j.beth.2019.05.011}, pmid = {32005331}, issn = {1878-1888}, mesh = {Adaptation, Psychological/*physiology ; Adolescent ; Adult ; Emotions/*physiology ; Fear/physiology/psychology ; Female ; Humans ; Male ; Middle Aged ; Phobia, Social/*psychology/*therapy ; Protective Factors ; Rumination, Cognitive/*physiology ; Social Behavior ; Students/psychology ; Young Adult ; }, abstract = {Rumination is thought to play a central role in affective disorders such as social anxiety disorder (SAD). Past research indicates that rumination tends to exacerbate negative emotions and increase the risk of engaging in maladaptive coping behaviors (e.g., avoiding social activities). However, little is known on how to effectively protect against the negative outcomes of rumination. Previously, Zaki, Coifman, Rafaeli, Berenson, and Downey (2013) found that negative emotion differentiation (NED) protected against rumination and nonsuicidal self-injury in borderline personality disorder. Nevertheless, it is unclear whether this protective effect would extend to other populations and behaviors. Therefore, the present investigation sought to replicate and extend Zaki et al.'s (2013) findings in the context of SAD. In two studies, we examined if NED would moderate the positive association between rumination and frequency of social avoidance. Study 1 involved 29 individuals who met criteria for SAD with or without co-occurring major depressive episode, while Study 2 involved a nonclinical sample of 190 college students. All participants completed a measure of rumination and an experience-sampling diary which provided indices of NED and social avoidance. The results from both studies were unanimous: NED significantly moderated the relationship between rumination and social avoidance such that the positive association between rumination and social avoidance was significant for low but not moderate to high NED. Overall, the findings provide a conceptual replication of Zaki et al. (2013) and further evidence for the protective effects of NED against the maladaptive behavioral consequences of rumination across populations.}, } @article {pmid32002669, year = {2020}, author = {Meshram, C and Lee, CC and Meshram, SG and Ramteke, RJ and Meshram, A}, title = {An Efficient Mobile-Healthcare Emergency Framework.}, journal = {Journal of medical systems}, volume = {44}, number = {3}, pages = {58}, pmid = {32002669}, issn = {1573-689X}, mesh = {Biometric Identification/*instrumentation ; Computer Security/*standards ; Emergency Service, Hospital/*organization & administration ; Humans ; Monitoring, Ambulatory/standards ; Remote Sensing Technology/*instrumentation ; Telemedicine/*instrumentation ; }, abstract = {Mobile technologies are capable of offering individual level health care services to users. Mobile Healthcare (m-Healthcare) frameworks, which feature smartphone (SP) utilizations of ubiquitous computing made possible by applying wireless Body Sensor Networks (BSNs), have been introduced recently to provide SP clients with health condition monitoring and access to medical attention when necessary. However, in a vulnerable m-Healthcare framework, clients' personal info and sensitive data can easily be poached by intruders or any malicious party, causing serious security problems and confidentiality issues. In 2013, Lu et al. proposed a mobile-Healthcare emergency framework based on privacy-preserving opportunistic computing (SPOC), claiming that their splendid SPOC construction can opportunistically gather SP resources such as computing power and energy to handle computing-intensive Personal Health Information (PHI) with minimal privacy disclosure during an emergency. To balance between the risk of personal health information exposure and the essential PHI processing and transmission, Lu et al. presented a patient-centric privacy ingress control framework based on an attribute-based ingress control mechanism and a Privacy-Preserving Scalar Product Computation (PPSPC) technique. In spite of the ingenious design, however, Lu et al.'s framework still has some security flaws in such aspects as client anonymity and mutual authentication. In this article, we shall offer an improved version of Lu et al.'s framework with the security weaknesses mended and the computation efficiency further boosted. In addition, we shall also present an enhanced mobile-Healthcare emergency framework using Partial Discrete Logarithm (PDL) which does not only achieve flawless mutual authentication as well as client anonymity but also reduce the computation cost.}, } @article {pmid32002139, year = {2020}, author = {Wang, W and Wu, X and Lan, X}, title = {Rumination mediates the relationships of fear and guilt to posttraumatic stress disorder and posttraumatic growth among adolescents after the Ya'an earthquake.}, journal = {European journal of psychotraumatology}, volume = {11}, number = {1}, pages = {1704993}, pmid = {32002139}, issn = {2000-8066}, abstract = {Background: Although previous research has demonstrated that fear and guilt have an effect on posttraumatic stress disorder (PTSD), it is still unclear how these two emotions affect posttraumatic growth (PTG). Moreover, few studies have examined the mechanisms by which fear and guilt affect PTSD and PTG. Guided by Lee et al.'s theory of PTSD generation mechanisms and Calhoun and Tedeschi's PTG theory, the current study proposes that intrusive rumination (IR) and deliberate rumination (DR) may play a mediating role in the effects of guilt and fear on PTSD and PTG. Objective: This study aimed to simultaneously examine the mediating roles of IR and DR in the relationship between fear, guilt, PTSD, and PTG. Method: This study employed a two-wave longitudinal design. A total of 408 adolescent survivors were assessed using self-report questionnaires after the Ya'an earthquake in China. Measures were obtained for trauma exposure, subjective fear, survivor guilt, IR, and DR at three and a half years after the Ya'an earthquake (Time 1), while PTSD and PTG were assessed at time point four and a half years after the Ya'an earthquake (Time 2). Results: The results showed that both fear and guilt had a direct and positive effect on PTSD and PTG. Fear and guilt were positive predictors of PTSD and negative predictors of PTG through the mediating variable of IR. DR mediated the relationship between guilt and PTG but not PTSD, and also mediated the relationship between IR and PTG. Conclusions: Study findings indicate that fear, guilt, and intrusive rumination may contribute to PTSD symptoms in adolescent trauma survivors. Results also suggest that adolescent survivors can grow emotionally and psychologically following traumatic events, and that directed rumination may contribute to such growth. Interventions that reduce fear, guilt, and intrusive rumination while increasing directed rumination may assist adolescent trauma survivors in recovery and growth.}, } @article {pmid32002102, year = {2020}, author = {Gregory, P and Austin, Z}, title = {Professional identity formation: The experience of regulated pharmacy technicians in Ontario.}, journal = {Canadian pharmacists journal : CPJ = Revue des pharmaciens du Canada : RPC}, volume = {153}, number = {1}, pages = {46-51}, pmid = {32002102}, issn = {1715-1635}, abstract = {BACKGROUND: Despite being regulated and spoken about as professionals, there is little formal research examining professional identity formation among regulated pharmacy technicians.

METHODS: A semistructured interview protocol was generated, based on Holden et al.'s typology of professional identity formation (PIF). Regulated pharmacy technicians in Ontario with a minimum of 2 years' experience working a minimum of 32 hours/week were recruited to participate. Interviews were transcribed, coded and analyzed based on professional identity formation.

RESULTS: A total of 15 regulated pharmacy technicians from southern Ontario participated in this study. Regardless of demographic background, most participants demonstrated identity splinting as the dominant form of professional identity formation. Issues related to social valuing of the role of the technician and environmental opportunities to develop and grow were highlighted as significant barriers.

INTERPRETATION: These findings suggest regulated pharmacy technicians have incomplete professional identities due in part to reasons linked to pharmacists and the pharmacy profession. The type of professional identity expressed by participants in this study may limit opportunities for full and optimal expression of their role.

CONCLUSIONS: Further work is necessary to better understand the professional identity formation of regulated pharmacy technicians, to help support the evolution of this role. Can Pharm J (Ott) 2020;153:xx-xx.}, } @article {pmid32001392, year = {2020}, author = {Mahavadi, AK and Patel, PM and Kuchakulla, M and Shah, AH and Eichberg, D and Luther, EM and Komotar, RJ and Ivan, ME}, title = {Central Neurocytoma Treatment Modalities: A Systematic Review Assessing the Outcomes of Combined Maximal Safe Resection and Radiotherapy with Gross Total Resection.}, journal = {World neurosurgery}, volume = {137}, number = {}, pages = {e176-e182}, doi = {10.1016/j.wneu.2020.01.114}, pmid = {32001392}, issn = {1878-8769}, mesh = {Brain Neoplasms/*therapy ; Combined Modality Therapy ; Humans ; Neoplasm Recurrence, Local/*epidemiology ; Neurocytoma/*therapy ; Neurosurgical Procedures/*methods ; Postoperative Complications/*epidemiology ; Radiotherapy, Adjuvant/*methods ; Treatment Outcome ; }, abstract = {BACKGROUND: Central neurocytomas (CNCs) are rare intraventricular lesions comprising <1% of primary brain tumors. Their surgical and adjuvant management is unclear.

OBJECTIVE: Our goal was to update Rades et al.'s 2006 systematic review to assess the outcome differences among 3 fundamental therapies for CNC: gross total resection with and without radiation therapy (RT) versus maximal safe resection with adjuvant RT.

METHODS: Articles indexed on PubMed and Google Scholar and published between January 1, 2006 and December 31, 2019 were selected using the PRISMA criteria. Studies were excluded if they had fewer than 3 cases, did not categorize extent of resection, or were duplicate studies, technical reports, case reports, or studies without follow-up. Complication rates, recurrence rates, overall survival and progression-free survival were extracted where possible. χ[2] proportionality tests were used for comparison (P values >0.05 suggested significance).

RESULTS: On aggregation, 615 patients from 13 studies including ours were assessed. Although overall survival was not significantly different (χ[2] = 1.56; P = 0.46), the recurrence rate differed significantly between GTR + RT (6.9%, 92.11 months), GTR-RT (23.9%, 96.8 months), and MSR + RT (16.8%, 85 months) (χ[2] = 10.94; P = 0.004). Pooled complication rates for GTR and MSR + RT were 31.2% and 24% (P = 0.049), respectively.

CONCLUSIONS: RT remains an important adjuvant treatment that can improve patient survival in the presence of MSR to levels comparable to those of GTR or GTR + RT. Where total resection carries too much risk, MSR + RT can be considered as the next best alternative for tumor control.}, } @article {pmid31998020, year = {2020}, author = {Amirshahi, M and Behnamfar, N and Badakhsh, M and Rafiemanesh, H and Keikhaie, KR and Sheyback, M and Sari, M}, title = {Prevalence of postoperative nausea and vomiting: A systematic review and meta-analysis.}, journal = {Saudi journal of anaesthesia}, volume = {14}, number = {1}, pages = {48-56}, pmid = {31998020}, issn = {1658-354X}, abstract = {OBJECTIVE: Postoperative nausea and vomiting (PONV) is a daily phenomenon, to which less attention has been paid in a variety of surgeries. Despite the individual studies, there is no comprehensive study on the prevalence of PONV. The aim of this study was to determine the global prevalence of PONV.

MATERIALS AND METHODS: In this systematic and meta-analysis study, descriptive studies of four databases (PubMed, Web of Science, Scopus, and Google Scholar) were searched for relevant texts from the time they were created until 31 December 2018. The random effects model was used for meta-analysis of studies included. All the steps were carried out by two individuals. Hoy et al.'s tool was used to evaluate its risk bias.

RESULTS: A total of 23 studies that were performed on 22,683 people from 11 countries were entered into the final phase. The prevalence of PONV, nausea, and vomiting was 27.7%, 31.4%, and 16.8%, respectively. The prevalence of PONV was higher during the first 24 h in European countries.

CONCLUSION: Considering the high prevalence of PONV and our goal to better control it, it is necessary to use high cost-effective approaches and recommendations and to educate health caregivers and patients.}, } @article {pmid31997304, year = {2020}, author = {Myszkowski, N and Çelik, P and Storme, M}, title = {Commentary on Corradi et al.'s (2019) new conception of aesthetic sensitivity: Is the ability conception dead?.}, journal = {British journal of psychology (London, England : 1953)}, volume = {111}, number = {4}, pages = {659-662}, doi = {10.1111/bjop.12440}, pmid = {31997304}, issn = {2044-8295}, mesh = {*Esthetics ; Humans ; *Perception ; }, abstract = {Corradi et al. (British Journal of Psychology, 2019) argue that their new conception of visual aesthetic sensitivity (as responsiveness to aesthetic features in one's preferences) presents several advantages in comparison with the current ability view of aesthetic sensitivity, usually defined as the ability to judge aesthetic stimuli in accordance with standards (The Journal of Psychology, 1964, 57 and 49). Although the measure they propose is interesting and presents advances to the field, we point to important issues. Notably, the authors conveniently base their comparison between the two conceptions on psychometric double standards, discard a century of research on aesthetic sensitivity by focusing on Eysenck's speculations, and disguise an extension of already existing aesthetic preference tests (e.g., The Journal of Psychology, 1952, 33 and 199; Empirical Studies of the Arts, 2005, 23 and 165) as a redefinition of aesthetic sensitivity. We conclude that both aesthetic preference and aesthetic sensitivity research are legitimate objects of study, that the authors present interesting ideas to further the study of aesthetic preferences, but that their approach is not new and that its proposed renaming only adds confusion to the field.}, } @article {pmid31989456, year = {2020}, author = {Brandmaier, AM and Ghisletta, P and Oertzen, TV}, title = {Optimal planned missing data design for linear latent growth curve models.}, journal = {Behavior research methods}, volume = {52}, number = {4}, pages = {1445-1458}, pmid = {31989456}, issn = {1554-3528}, mesh = {Computer Simulation ; Humans ; *Linear Models ; Longitudinal Studies ; Monte Carlo Method ; *Research Design ; }, abstract = {Longitudinal data collection is a time-consuming and cost-intensive part of developmental research. Wu et al. (2016) discussed planned missing (PM) designs that are similar in efficiency to complete designs but require fewer observations per person. The authors reported optimal PM designs for linear latent growth curve models based on extensive Monte Carlo simulations. They called for further formal investigation of the question as to how much the proposed PM mechanisms influence study design efficiency to arrive at a better understanding of PM designs. Here, we propose an approximate solution to the design problem by comparing the asymptotic effective errors of PM designs. Effective error was previously used to find optimal longitudinal study designs for complete data designs; here, we extend the approach to planned missing designs. We show how effective error is a metric for comparing the efficiency of study designs with both planned and unplanned missing data, and how earlier simulation-based results for PM designs can be explained by an asymptotic solution. Our approach is computationally more efficient than Wu et al.'s approach and leads to a better understanding of how various design factors, such as the number of measurement occasions, their temporal arrangement, attrition rates, and PM design patterns interact and how they conjointly determine design efficiency. We provide R scripts to calculate effective errors in various scenarios of PM designs.}, } @article {pmid31989239, year = {2020}, author = {Kacem, H and Giese, EG and Miquel, J}, title = {Sperm characters in the Hemiuridae (Digenea): first data on Aphanurus stossichii (Aphanurinae) and Ectenurus lepidus (Dinurinae).}, journal = {Parasitology research}, volume = {119}, number = {3}, pages = {991-999}, pmid = {31989239}, issn = {1432-1955}, mesh = {Animals ; Axoneme/ultrastructure ; Cell Membrane/ultrastructure ; Cell Nucleus/ultrastructure ; Fishes/parasitology ; Gastrointestinal Tract/parasitology ; Male ; Mediterranean Sea ; Microtubules/ultrastructure ; Mitochondria/ultrastructure ; Spermatozoa/*ultrastructure ; Trematoda/*cytology/ultrastructure ; Trematode Infections/parasitology/veterinary ; Tunisia ; }, abstract = {The present work provides the first ultrastructural analysis of spermatozoa of two digeneans (Aphanurus stossichii (Monticelli, 1891) and Ectenurus lepidus Looss, 1907) belonging to the unexplored subfamilies of the Hemiuridae, namely, the Aphanurinae and the Dinurinae. In March 2019, these hemiurids were collected respectively from the digestive tract of the bogue Boops boops (Teleostei, Sparidae) and the Atlantic horse mackerel Trachurus trachurus (Teleostei, Carangidae) captured in the coastal zone of the Mediterranean Sea, off La Chebba (Tunisia). The ultrastructural study reveals that both spermatozoa exhibit the Bakhoum et al.'s type II of the digenean sperm cells characterized by the presence of two 9+'1' axonemes, an external ornamentation of the plasma membrane not associated with cortical microtubules and located in the anterior part of the spermatozoon, a single bundle of cortical microtubules, the maximum number of cortical microtubules located in a middle part of the sperm cell, and one mitochondrion. Moreover, they share several ultrastructural features with the studied spermatozoa of Hemiuridae such as the presence of two axonemes with the 9+'1' trepaxonematan pattern, a reduced number of parallel cortical microtubules organized into one field with their maximum number located in the median (A. stossichii) or posterior (E. lepidus) part of the spermatozoon, an external ornamentation of the plasma membrane in the anterior part of the spermatozoon, one mitochondrion, a nucleus, and a small amount of glycogen granules. However, the two studied hemiurids could be distinguished by the morphology of the anterior and posterior spermatozoon extremities and the presence of mitochondrial matrix granules in A. stossichii.}, } @article {pmid31983625, year = {2020}, author = {Donovan, E and Bratberg, J and Baird, J and Burstein, D and Case, P and Walley, AY and Green, TC}, title = {Pharmacy leaders' beliefs about how pharmacies can support a sustainable approach to providing naloxone to the community.}, journal = {Research in social & administrative pharmacy : RSAP}, volume = {16}, number = {10}, pages = {1493-1497}, doi = {10.1016/j.sapharm.2020.01.006}, pmid = {31983625}, issn = {1934-8150}, support = {R18 HS024021/HS/AHRQ HHS/United States ; }, mesh = {*Community Pharmacy Services ; *Drug Overdose/drug therapy ; Humans ; Massachusetts ; Naloxone/therapeutic use ; Narcotic Antagonists/therapeutic use ; *Opioid-Related Disorders/drug therapy ; *Pharmacies ; Pharmacists ; *Pharmacy ; Rhode Island ; }, abstract = {BACKGROUND: Naloxone is an antidote to opioid overdose, and community pharmacies nationwide now provide broad access to this medication.

OBJECTIVE: The aim of this qualitative study was to understand how leaders in pharmacy organizations perceive pharmacies and pharmacy staff can optimize dispensing of naloxone.

METHODS: In-depth interviews were conducted with 12 pharmacy leaders in Massachusetts and Rhode Island. Participants were recruited from three types of community pharmacies: (1) chain; (2) independent; and (3) hospital outpatient. Theory-driven immersion crystallization, using Brownlee et al.'s model of healthcare quality improvement, was used to inform coding of the interview data, with predetermined categories of staff; organization; and process.

RESULTS: Five main themes were identified: (1) Importance of staff training to increase comfort; (2) Strength through coordination of efforts; (3) Pharmacy as a community leader in the opioid crisis; (4) Persisting stigma; and (5) Ongoing workflow challenges.

CONCLUSIONS: The results uniquely reflect the experiences and insights of pharmacy leaders implementing public health initiatives during the opioid crisis and can be used for gaining insight into how pharmacists can efficiently provide naloxone to their communities.}, } @article {pmid31981850, year = {2020}, author = {Nadarevic, L and Kroneisen, M}, title = {Easy on the mind, easy on the wrongdoer? No evidence for perceptual fluency effects on moral wrongness ratings.}, journal = {Cognition}, volume = {196}, number = {}, pages = {104156}, doi = {10.1016/j.cognition.2019.104156}, pmid = {31981850}, issn = {1873-7838}, mesh = {Cognition ; Emotions ; Humans ; *Judgment ; *Morals ; Recognition, Psychology ; }, abstract = {Processing fluency-the subjective ease of information processing-influences a variety of judgments (e.g., judgments of familiarity, liking, and truth). A study by Laham, Alter, and Goodwin (2009) suggests that this is also true for moral judgments. More specifically, the authors found that discrepant perceptual fluency mitigates moral wrongness ratings. In five studies (total N = 694), we tested the replicability of this finding for different kinds of scenarios (moral versus conventional transgressions) and different perceptual fluency manipulations. In Studies 1a and 1b we manipulated fluency by text background, in Studies 2a and 2b by font type, and in Study 3 by word spaces. Critically, none of the studies replicated Laham et al.'s discrepant fluency effect on moral wrongness ratings. In turn, we found that moral wrongness ratings were strongly affected by participants' emotional responses to the scenarios. Taken together, the findings of our five studies cast very strong doubt on perceptual fluency effects on moral judgments.}, } @article {pmid31980505, year = {2020}, author = {Rasiah, S and Jaafar, S and Yusof, S and Ponnudurai, G and Chung, KPY and Amirthalingam, SD}, title = {A study of the nature and level of trust between patients and healthcare providers, its dimensions and determinants: a scoping review protocol.}, journal = {BMJ open}, volume = {10}, number = {1}, pages = {e028061}, pmid = {31980505}, issn = {2044-6055}, mesh = {Health Personnel/*psychology ; Humans ; Patients/*psychology ; Private Sector ; Professional-Patient Relations ; Public Sector ; Research Design ; Trust/*psychology ; Scoping Reviews As Topic ; }, abstract = {INTRODUCTION: The aim of this scoping review is to systematically search the literature to identify the nature and or level of trust between the patient, the users of health services (eg, clients seeking health promotion and preventive healthcare services) and the individual healthcare providers (doctors, nurses and physiotherapists/ occupational therapists), across public and private healthcare sectors, at all levels of care from primary through secondary to tertiary care. It also aims to identify the factors that influence trust between patients, users of health services (clients) and providers of healthcare at all levels of care from primary care to tertiary care, and across all health sectors (public and private). The study will also identify the tools used to measure trust in the healthcare provider.

METHODS AND ANALYSIS: The scoping review will be conducted based on the methodology developed by Arksey and O'Malley's scoping review methodology, and Levac et al 's methodological enhancement. An experienced information specialist (HM) searched the following databases MEDLINE, EMBASE, the Cochrane Library, Cumulative Index to Nursing and Allied Health Literature. The search terms were both keywords in the title and/or abstract and subject headings (eg, MeSH, EMTREE) as appropriate. Search results were downloaded, imported and stored into a 'Refworks' folder specifically created for reference management. The preliminary search was conducted between 7 December 2017 and 14 December 2017. Quantitative methods using content analysis will be used to categorise study findings on factors associated with trust between patients, clients and healthcare providers. The collection of studies will be also examined for heterogeneity. Qualitative analysis on peer reviewed articles of qualitative interviews and focus group discussion will be conducted; it allows clear identification of themes arising from the data, facilitating prioritisation, higher order abstraction and theory development. A consultation exercise with stakeholders may be incorporated as a knowledge translation component of the scoping study methodology.

ETHICS AND DISSEMINATION: Ethical approval will be obtained for the research project from the Institutional Review Board. The International Medical University will use the findings of this scoping review research to improve the understanding of trust in healthcare, in its endeavour to improve health services delivery in its healthcare clinics and hospitals, and in its teaching and learning curriculum. The findings will also help faculty make evidence based decisions to focus resources and research as well as help to advance the science in this area. Dissemination of the results of the scoping review will be made through peer-reviewed publications, research reports and presentations at conferences and seminars.}, } @article {pmid31964474, year = {2020}, author = {Newton, JC and Hohnen, H and Johnson, CE and Ives, A and McKiernan, S and Platt, V and Saunders, C and Slavova-Azmanova, N}, title = {'…If I don't have that sort of money again, what happens?': adapting a qualitative model to conceptualise the consequences of out-of-pocket expenses for cancer patients in mixed health systems.}, journal = {Australian health review : a publication of the Australian Hospital Association}, volume = {44}, number = {3}, pages = {355-364}, doi = {10.1071/AH18250}, pmid = {31964474}, issn = {1449-8944}, mesh = {Adaptation, Psychological ; Adult ; Aged ; *Attitude to Health ; *Cost of Illness ; Female ; Health Expenditures ; Health Services Accessibility ; Humans ; Interviews as Topic ; Male ; Middle Aged ; Neoplasms/*economics/*psychology/therapy ; Qualitative Research ; Universal Health Insurance ; Western Australia ; }, abstract = {Objective The aim of this study was to explore Western Australian cancer patients' experiences of out-of-pocket expenses (OOPE) during diagnosis and cancer treatment using a phenomenological approach. Methods Semi-structured interviews were conducted with a purposive convenience sample of 40 Western Australian cancer patients diagnosed with breast, lung, prostate or colorectal cancer. Participants were asked about the impact of their diagnosis, the associated costs and their experience within the health system. Data were analysed using thematic content analysis. Results Three key themes influencing participant OOPE experiences were identified: (1) personal circumstances; (2) communication with health providers; and (3) coping strategies. Despite Australia's public healthcare system, several participants found the costs affected their financial security and resorted to coping strategies including medication rationing and restrictive household budgeting. The key themes had a complex and interrelated effect on patient OOPE experiences and were used to adapt Carrera et al.'s model of economic consequences of cancer treatment on the patient and patient coping to describe these relationships in a mixed healthcare system. Conclusion Organised efforts must be implemented to mitigate maladaptive coping strategies being used by cancer patients: (1) health providers should seek informed financial consent from patients before commencing treatment; and (2) financial aid and support schemes for cancer patients should be reviewed to ensure they are delivered equitably. What is known on this topic? The financial cost of cancer can have significant adverse effects on cancer patients. Although financial transparency is desired by cancer patients, its implementation in practice is not clear. What does this paper add? This study adapts a conceptual model for the economic consequences of a cancer diagnosis and repurposes it for a mixed public-private health system, providing a framework for understanding downstream consequences of cancer costs and highlighting opportunities for intervention. What are the implications for health practitioners? Health practitioners need to initiate discussions concerning treatment costs earlier with cancer patients. There are several resources and guides available to assist and facilitate financial transparency. Without urgent attention to the financial consequences of cancer treatment and related expenses, we continue to leave patients at risk of resorting to maladaptive coping strategies, such as medication rationing and restrictive household budgeting.}, } @article {pmid31961845, year = {2020}, author = {Mahon, SM}, title = {Considerations for the Telephone Disclosure of Genetic Test Results to Patients With Cancer.}, journal = {Clinical journal of oncology nursing}, volume = {24}, number = {1}, pages = {8}, doi = {10.1188/20.CJON.8}, pmid = {31961845}, issn = {1538-067X}, mesh = {*Disclosure ; Genetic Counseling ; Genetic Testing ; Humans ; *Neoplasms ; Patient Preference ; Telephone ; }, abstract = {I would like to thank Cantril, Moore, and Yan (2019) for their informative article on patient preferences for the disclosure of a breast cancer diagnosis in the December issue of the Clinical Journal of Oncology Nursing. The findings of Cantril et al.'s (2019) study suggest that patients prefer in-person disclosure. Additional patient priorities included knowing the results of tests quickly, having those results disclosed by an expert with a sensitive touch, and having a clear understanding of the next steps in the treatment plan.}, } @article {pmid31947093, year = {2019}, author = {McCay, KD and Ho, ESL and Marcroft, C and Embleton, ND}, title = {Establishing Pose Based Features Using Histograms for the Detection of Abnormal Infant Movements.}, journal = {Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference}, volume = {2019}, number = {}, pages = {5469-5472}, doi = {10.1109/EMBC.2019.8857680}, pmid = {31947093}, issn = {2694-0604}, mesh = {*Algorithms ; Child Development ; Cluster Analysis ; Data Interpretation, Statistical ; Discriminant Analysis ; Humans ; Infant ; *Movement ; Pilot Projects ; }, abstract = {The pursuit of early diagnosis of cerebral palsy has been an active research area with some very promising results using tools such as the General Movements Assessment (GMA). In this paper, we conducted a pilot study on extracting important information from video sequences to classify the body movement into two categories, normal and abnormal, and compared the results provided by an independent expert reviewer based on GMA. We present two new pose-based features, Histograms of Joint Orientation 2D (HOJO2D) and Histograms of Joint Displacement 2D (HOJD2D), for the pose-based analysis and classification of infant body movement from video footage. We extract the 2D skeletal joint locations from 2D RGB images using Cao et al.'s method [1]. Using the MINI-RGBD dataset [2], we further segment the body into local regions to extract part specific features. As a result, the pose and the degree of displacement are represented by histograms of normalised data. To demonstrate the effectiveness of the proposed features, we trained several classifiers using combinations of HOJO2D and HOJD2D features and conducted a series of experiments to classify the body movement into categories. The classification algorithms used included k-Nearest Neighbour (kNN, k=1 and k=3), Linear Discriminant Analysis (LDA) and the Ensemble classifier. Encouraging results were attained, with high accuracy (91.67%) obtained using the Ensemble classifier.}, } @article {pmid31928292, year = {2020}, author = {Takahashi, M and Yamamoto, Y and Koizumi, H and Motegi, M and Komori, M and Yamamoto, K and Yaguchi, Y and Kojima, H}, title = {The relationships among mastoid air cell development, tympanic sinus depth, and residual disease after surgery in children with congenital cholesteatoma.}, journal = {Acta oto-laryngologica}, volume = {140}, number = {4}, pages = {286-288}, doi = {10.1080/00016489.2020.1712475}, pmid = {31928292}, issn = {1651-2251}, mesh = {Adolescent ; Child ; Child, Preschool ; Cholesteatoma/*congenital/pathology/surgery ; Cholesteatoma, Middle Ear/*pathology/surgery ; Ear, Middle/*pathology ; Female ; Humans ; Male ; Mastoid/*pathology ; Mastoidectomy ; Retrospective Studies ; }, abstract = {Background: Mastoid development, tympanic sinus depth, and residual disease after surgery for congenital cholesteatoma are probably related, but these relationships have not been examined in detail.Aims/objectives: This study aimed to clarify the relationships between the abovementioned factors. Materials and Methods: The subjects were 31 patients with congenital cholesteatoma (stage III or IV in Potsic's staging system) that underwent mastoidectomy. The cross-sectional area of the mastoid air cells was measured as described previously. Tympanic sinus depth was classified into A-C using Marchioni et al.'s system.Results: Patients with deep tympanic sinuses or residual disease exhibited significantly greater mastoid air cell development. However, little residual disease was found in the mastoid air cells. Conversely, residual disease was observed more frequently in the patients with deep tympanic sinuses.Conclusions and significance: After surgery for congenital cholesteatoma, residual disease is more likely to occur in patients with marked mastoid growth, possibly because they have deep tympanic sinuses. Cases in which congenital cholesteatoma spreads to the mastoid air cells are classified as stage IV in Potsic's system, but our findings indicate that invasion into a deep tympanic sinus is more important than invasion into the mastoid air cells.}, } @article {pmid31922273, year = {2020}, author = {Abbott, L and Scott, T and Thomas, H and Weston, K}, title = {Pregnancy and childbirth in English prisons: institutional ignominy and the pains of imprisonment.}, journal = {Sociology of health & illness}, volume = {42}, number = {3}, pages = {660-675}, pmid = {31922273}, issn = {1467-9566}, mesh = {Adaptation, Psychological ; Child ; England ; Female ; Humans ; Parturition ; Pregnancy ; *Prisoners ; *Prisons ; }, abstract = {With a prison population of approximately 9000 women in England, it is estimated that approximately 600 pregnancies and 100 births occur annually. Despite an extensive literature on the sociology of reproduction, pregnancy and childbirth among women prisoners is under-researched. This article reports an ethnographic study in three English prisons undertaken in 2015-2016, including interviews with 22 prisoners, six women released from prison and 10 staff members. Pregnant prisoners experience numerous additional difficulties in prison including the ambiguous status of a pregnant prisoner, physical aspects of pregnancy and the degradation of the handcuffed or chained prisoner during visits to the more public setting of hospital. This article draws on Erving Goffman's concepts of closed institutions, dramaturgy and mortification of self, Crewe et al.'s work on the gendered pains of imprisonment and Crawley's notion of 'institutional thoughtlessness', and proposes a new concept of institutional ignominy to understand the embodied situation of the pregnant prisoner.}, } @article {pmid31917079, year = {2020}, author = {Yu, S and Fabbro, M and Aljure, O}, title = {Expert Consensus Systems of Care Proposal to Optimize Care for Patients With Valvular Heart Disease Review of the 2019 Document for the Cardiac Anesthesiologist.}, journal = {Journal of cardiothoracic and vascular anesthesia}, volume = {34}, number = {9}, pages = {2476-2483}, doi = {10.1053/j.jvca.2019.11.034}, pmid = {31917079}, issn = {1532-8422}, mesh = {Adult ; Anesthesiologists ; Cardiac Catheterization ; Consensus ; Echocardiography ; *Heart Valve Diseases/diagnostic imaging/surgery ; *Heart Valve Prosthesis Implantation ; Humans ; }, abstract = {Valvular heart disease requiring intervention is increasing in prevalence in the adult population. With advancement in transcatheter and surgical procedures for valvular heart disease, optimization of patient selection, availability of resources and personnel, appropriate training and certification, and optimal periprocedural management rely on clinical evaluation, accurate echocardiographic interpretation, and understanding of valvular pathophysiology by the cardiac anesthesiologist. To optimize care and improve access for patients with valvular heart disease the Expert Consensus Systems of Care Document by Nishimura et al.[1] was recently published. The authors propose a protocol with guidelines and performance metrics to create tiered-level valve centers. This review focuses and expands on aspects discussed in Nishimura et al.'s Expert Consensus Systems of Care Document that are relevant to the cardiac anesthesiologist in the periprocedural setting.}, } @article {pmid31906795, year = {2020}, author = {Vancak, V and Goldberg, Y and Levine, SZ}, title = {Systematic analysis of the number needed to treat.}, journal = {Statistical methods in medical research}, volume = {29}, number = {9}, pages = {2393-2410}, doi = {10.1177/0962280219890635}, pmid = {31906795}, issn = {1477-0334}, abstract = {The number needed to treat is often used to measure the efficacy of a binary outcome in randomized clinical trials. There are three different available measures of the number needed to treat. Two of these measures, Furukawa and Leucht's and Kraemer and Kupfer's, focus on converting Cohen's δ index into the number needed to treat, while Laupacis et al.'s measure deals primarily with the number needed to treat's estimation rather than with a reformulation. Mathematical and numerical analysis of numbers needed to treat and their estimators was conducted. Three novel number needed to treat estimators were introduced to supplement the numbers needed to treat introduced by Laupacis, Furukawa and Leucht, and Kraemer and Kupfer. The analysis showed that Laupacis et al.'s number needed to treat is intrinsically different from Kraemer and Kupfer's number needed to treat, and that Furukawa and Leucht's estimator is appropriate to use only for normally distributed outcomes with equal standard deviations. Based on the numerical analysis, the novel numbers needed to treat outperformed the existing ones under correct model specifications. Asymptotic analysis was used to test three different types of confidence intervals to supplement the numbers needed to treat. An R-package to calculate these numbers needed to treat and their confidence intervals has been developed and made available for users online.}, } @article {pmid31901562, year = {2020}, author = {He, Q and Brown, TI}, title = {Heterogeneous correlations between hippocampus volume and cognitive map accuracy among healthy young adults.}, journal = {Cortex; a journal devoted to the study of the nervous system and behavior}, volume = {124}, number = {}, pages = {167-175}, pmid = {31901562}, issn = {1973-8102}, support = {R21 AG063131/AG/NIA NIH HHS/United States ; }, mesh = {Aptitude ; Cognition ; *Hippocampus/diagnostic imaging ; Humans ; Spatial Learning ; *Spatial Navigation ; Young Adult ; }, abstract = {Marked individual differences in the ability to mentally map our environment are pronounced not only among people of different ages or clinical conditions, but also within healthy young adults. Previous studies have shown that hippocampus size positively correlated with spatial navigation ability in healthy young adults, navigation experts, and patients with hippocampus lesions. However, a recent pre-registered study (Weisberg, Newcombe, & Chatterjee, 2019) with a large sample size (n = 90) did not observe this correlation in healthy young adults. Motivated by evidence that self-report sense of direction (SOD) could have a profound impact on how individuals utilize environmental cues, and that different navigation strategies could have opposite impacts on wayfinding performance in individuals with different cognitive map formation (CMF) abilities, we reanalyzed the publicly available dataset from Weisberg et al.'s study. We tested the influence of participants' SOD and CMF abilities on hippocampal volume-performance relationships. We find evidence that the non-significant correlation could envelop heterogeneous correlations among subgroups of individuals: the correlation between the right posterior hippocampal volume and spatial learning performance is significantly higher among individuals with high spatial ability than individuals with low spatial ability. This pattern of performance was observed for both SOD and CMF moderations of the relationship between hippocampal volume and spatial learning. While our re-analyses are fundamentally exploratory in nature, the new results imply that the relationship between hippocampal volume and spatial learning performance might be more complicated than previously thought.}, } @article {pmid31899591, year = {2020}, author = {Nobandegani, AS and Shultz, TR}, title = {A Resource-Rational, Process-Level Account of the St. Petersburg Paradox.}, journal = {Topics in cognitive science}, volume = {12}, number = {1}, pages = {417-432}, doi = {10.1111/tops.12486}, pmid = {31899591}, issn = {1756-8765}, support = {//Natural Sciences and Engineering Research Council of Canada/International ; }, mesh = {Adult ; *Decision Making/physiology ; Humans ; *Models, Psychological ; *Reward ; *Risk-Taking ; }, abstract = {The St. Petersburg paradox is a centuries-old philosophical puzzle concerning a lottery with infinite expected payoff for which people are only willing to pay a small amount to play. Despite many attempts and several proposals, no generally accepted resolution is yet at hand. In this work, we present the first resource-rational, process-level explanation of this paradox, demonstrating that it can be accounted for by a variant of normative expected utility valuation which acknowledges cognitive limitations. Specifically, we show that Nobandegani et al.'s (2018) metacognitively rational model, sample-based expected utility (SbEU), can account for major experimental findings on this paradox. Crucially, our resolution is consistent with two empirically well-supported assumptions: (a) People use only a few samples in probabilistic judgments and decision-making, and (b) people tend to overestimate the probability of extreme events in their judgment. Our work seeks to understand the St. Petersburg gamble as a particularly risky gamble whose process-level explanation is consistent with a broader process-level model of human decision-making under risk.}, } @article {pmid31898305, year = {2020}, author = {Karasakal, A}, title = {Determination of Trace and Major Elements in Vegan Milk and Oils by ICP-OES After Microwave Digestion.}, journal = {Biological trace element research}, volume = {197}, number = {2}, pages = {683-693}, pmid = {31898305}, issn = {1559-0720}, mesh = {Animals ; Digestion ; Humans ; Hydrogen Peroxide ; *Microwaves ; Oils ; *Trace Elements/analysis ; Turkey ; Vegans ; }, abstract = {Increasing technological developments also bring about environmental pollution. Heavy metals and metallic compounds, as a result of soil, water, and air industrialization, pass through to people and animals through the food chain and have a negative impact on health. In this study, the concentrations of Na, Mg, K, Ca, P, Fe, Cu, B, Mn, Zn, Al, S, As, Bi, Cd, Co, Cr, Mo, Ni, Pb, Pt, Sb, Se, Sn, Ti, W, and Hg in commercial vegan milk (soybean milk, coconut milk, and almond milk) and oils (soybean oil, coconut oil, bitter almond oil, sweet almond oil, and walnut oil) were determinated using inductively coupled plasma-optical emission spectrometry after microwave digestion. In order to compare the efficiencies of digestion in vegan milk and oil samples, 6 mL of HNO3 (conc.), 3 mL of H2O2 (30%); 7 mL of HNO3 (conc.), 3.5 mL of H2O2 (30%), and 8 mL of HNO3 (conc.), 4 mL of H2O2 (30%) were used in microwave digestion procedures. The proposed procedures were applied to the analysis of 81 vegan milk and 125 vegan oil samples covering three different brands in Turkey. Na, Mg, K, Ca, P, S, Mn, Zn, Cu, B, Sb, and Sn concentrations in vegan milks ranged (minimum-maximum in ppm) as follows: 307.4-501.2, 1.8-15.6, 478.8-1300.4, 276.3-1189, 197-797.8, 18.7-241.4, 0.09-0.42, 0-0.58, 0.02-1.06, 0.34-1.56, 0.26-0.67, and 3.4-30.4 ppm, respectively. The results of Na, K, Ca, P, Mg, S, Mn, Zn, Se, Fe, Cu, Sb, and Sn concentrations in vegan oils (minimum-maximum in ppm) ranged as follows: 6.8-31.2, 403.5-425.2, 142.8-160.4, 71.65-149.8, 0.35-0.85, 14.2-35.2, 0.02-0.27, 0.07-0.36, 1.90-4.64, 0.92-5.36, 0.01-0.05, 1.02-1.66, and 21.2, 35.0 ppm, respectively. Vegan milk contents except for Se, Fe, Sb, and Sn in this study were higher than vegan oil contents. The methods were validated by linearity, limits of detection and quantification, precision, and analyzing certified reference material (NIST SRM-3235), soybean milk. The highest values of LOD were found Pb, P, and Bi, and the highest values of LOQ were found Mo, Pb, and Sb.}, } @article {pmid31896362, year = {2020}, author = {Strikwerda-Brown, C and Irish, M}, title = {The other side of the coin: Semantic dementia as a lesion model for understanding recollection and familiarity.}, journal = {The Behavioral and brain sciences}, volume = {42}, number = {}, pages = {e300}, doi = {10.1017/S0140525X19001894}, pmid = {31896362}, issn = {1469-1825}, mesh = {*Frontotemporal Dementia ; Humans ; Memory ; Memory Disorders ; Mental Recall ; Recognition, Psychology ; }, abstract = {The syndrome of semantic dementia represents the "other side of the coin" to Alzheimer's disease, offering convergent evidence to help refine Bastin et al.'s integrative memory model. By considering the integrative memory model through the lens of semantic dementia, we propose a number of important extensions to the framework, to help clarify the complex neurocognitive mechanisms underlying recollection and familiarity.}, } @article {pmid31896350, year = {2020}, author = {Sadeh, T}, title = {Fluency: A trigger of familiarity for relational representations?.}, journal = {The Behavioral and brain sciences}, volume = {42}, number = {}, pages = {e297}, doi = {10.1017/S0140525X1900178X}, pmid = {31896350}, issn = {1469-1825}, mesh = {Humans ; *Memory ; Memory Disorders ; Mental Recall ; *Recognition, Psychology ; Social Perception ; }, abstract = {According to Bastin et al.'s integrative memory model, familiarity may be attributed to both entity representations and relational representations. However, the model does not specify what triggers familiarity for relational representations. I argue that fluency is a key player in the attribution of familiarity regardless of the type of representation. Two lines of evidence are reviewed in support of my claim.}, } @article {pmid31892412, year = {2020}, author = {Jaramillo, R and Dorman, FL}, title = {Retention time prediction of hydrocarbons in cryogenically modulated comprehensive two-dimensional gas chromatography: A method development and translation application.}, journal = {Journal of chromatography. A}, volume = {1612}, number = {}, pages = {460696}, doi = {10.1016/j.chroma.2019.460696}, pmid = {31892412}, issn = {1873-3778}, mesh = {Chromatography, Gas/*methods ; Gas Chromatography-Mass Spectrometry ; Hydrocarbons/*analysis/chemistry ; Thermodynamics ; }, abstract = {Thermodynamic modeling of GC × GC separations provides a tool for rapid method evaluation and optimization. Separations of 95 hydrocarbons on two cryogenically modulated GC × GC systems (atmospheric outlet and vacuum outlet) are modeled, displaying average second dimension retention time modeling absolute errors of 0.17 s and 0.12 s respectively, and generating modeled chromatograms which sufficiently represent experimental data. A web-based GC × GC modeling routine is presented which allows users to model separations, currently focused on hydrocarbons, with full control over all system parameters. The method translation capabilities of the application are further demonstrated by replicating Piotrowski et al.'s GC × GC-HRT temporal distribution plots of hydraulic fracturing flowback fluid hydrocarbons [28].}, } @article {pmid33829212, year = {2020}, author = {Robles, G and Sauermilch, D and Starks, TJ}, title = {Self-efficacy, social distancing, and essential worker status dynamics among SGM people.}, journal = {Annals of LGBTQ public and population health}, volume = {1}, number = {4}, pages = {300-317}, pmid = {33829212}, issn = {2688-4518}, support = {R01 DA045613/DA/NIDA NIH HHS/United States ; }, abstract = {As of October 2020, the COVID-19 pandemic has accounted for over 210,000 deaths in the U.S. Sexual and gender minority populations are more likely to work in essential industries while bearing a disproportionate burden of the virus. Constructs consistent with Protection Motivation Theory (perceived severity, vulnerability, self-efficacy, and response efficacy) were measured using an abridged version of Kleczkowski et al.'s 4-factor Protection Motivation Theory Psychological Measures to examine social distancing behaviors of these populations. 32.6% of the sample were essential workers. Greater self-efficacy predicted stricter social distancing behaviors. Non-essential and unemployed worker statuses were associated with increased odds of stricter social distancing behaviors relative to essential worker status. Essential worker status predicted lower self-efficacy. The indirect effect of essential worker status on social distancing through self-efficacy was significant. Findings suggest that interventions that encourage social distancing through enhanced self-efficacy may optimize health for sexual and gender minority essential workers.}, } @article {pmid31890613, year = {2019}, author = {Christie, HL and Martin, JL and Connor, J and Tange, HJ and Verhey, FRJ and de Vugt, ME and Orrell, M}, title = {eHealth interventions to support caregivers of people with dementia may be proven effective, but are they implementation-ready?.}, journal = {Internet interventions}, volume = {18}, number = {}, pages = {100260}, pmid = {31890613}, issn = {2214-7829}, abstract = {OBJECTIVES: A variety of health services delivered via the Internet, or "eHealth interventions," to support caregivers of people with dementia have shown evidence of effectiveness, but only a small number are put into practice. This study aimed to investigate whether, how and why their implementation took place.

METHODS: This qualitative study followed up on the 12 publications included in Boots et al.'s (2014) widely cited systematic review on eHealth interventions for informal caregivers of people with dementia, in order to explore further implementation into practice. Publicly available online information, implementation readiness (ImpRess checklist scores), and survey responses were assessed.

FINDINGS: Two interventions were freely available online, two were available in a trial context, and one was exclusively available to clinical staff previously involved in the research project. The remaining seven were unavailable. All scores on the ImpRess checklist were at 50% or lower of the total, indicating that the interventions were not ready to implement at the time of the Boots et al. (2014) review, though some interventions were scored as more implementation-ready in subsequent follow-up publications. Responses to the survey were received from six out of twelve authors. Key learnings from the survey included the importance of the involvement of stakeholders at all stages of the process, as well as the flexible adaptation and commercialization of the intervention.

CONCLUSIONS: In general, low levels of implementation readiness were reported and often the information necessary to assess implementation readiness was unavailable. The only two freely available interventions had long-term funding from aging foundations. Authors pointed to the involvement of financial gatekeepers in the development process and the creation of a business model early on as important facilitators to implementation. Future research should focus on the factors enabling sustainable implementation.}, } @article {pmid31883529, year = {2019}, author = {Cougnoux, A and Drummond, RA and Fellmeth, M and Navid, F and Collar, AL and Iben, J and Kulkarni, AB and Pickel, J and Schiffmann, R and Wassif, CA and Cawley, NX and Lionakis, MS and Porter, FD}, title = {Unique molecular signature in mucolipidosis type IV microglia.}, journal = {Journal of neuroinflammation}, volume = {16}, number = {1}, pages = {276}, pmid = {31883529}, issn = {1742-2094}, support = {ZIA HD000139/HD/NICHD NIH HHS/United States ; ZIA AI001175/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Fabry Disease/genetics/metabolism/pathology ; Humans ; Mice ; Mice, Transgenic ; Microglia/*metabolism/pathology ; Mucolipidoses/*genetics/metabolism/*pathology ; *Transcriptome ; }, abstract = {BACKGROUND: Lysosomal storage diseases (LSD) are a large family of inherited disorders characterized by abnormal endolysosomal accumulation of cellular material due to catabolic enzyme and transporter deficiencies. Depending on the affected metabolic pathway, LSD manifest with somatic or central nervous system (CNS) signs and symptoms. Neuroinflammation is a hallmark feature of LSD with CNS involvement such as mucolipidosis type IV, but not of others like Fabry disease.

METHODS: We investigated the properties of microglia from LSD with and without major CNS involvement in 2-month-old mucolipidosis type IV (Mcoln1[-/-]) and Fabry disease (Gla[y/-]) mice, respectively, by using a combination of flow cytometric, RNA sequencing, biochemical, in vitro and immunofluorescence analyses.

RESULTS: We characterized microglia activation and transcriptome from mucolipidosis type IV and Fabry disease mice to determine if impaired lysosomal function is sufficient to prime these brain-resident immune cells. Consistent with the neurological pathology observed in mucolipidosis type IV, Mcoln1[-/-] microglia demonstrated an activation profile with a mixed neuroprotective/neurotoxic expression pattern similar to the one we previously observed in Niemann-Pick disease, type C1, another LSD with significant CNS involvement. In contrast, the Fabry disease microglia transcriptome revealed minimal alterations, consistent with the relative lack of CNS symptoms in this disease. The changes observed in Mcoln1[-/-] microglia showed significant overlap with alterations previously reported for other common neuroinflammatory disorders including Alzheimer's, Parkinson's, and Huntington's diseases. Indeed, our comparison of microglia transcriptomes from Alzheimer's disease, amyotrophic lateral sclerosis, Niemann-Pick disease, type C1 and mucolipidosis type IV mouse models showed an enrichment in "disease-associated microglia" pattern among these diseases.

CONCLUSIONS: The similarities in microglial transcriptomes and features of neuroinflammation and microglial activation in rare monogenic disorders where the primary metabolic disturbance is known may provide novel insights into the immunopathogenesis of other more common neuroinflammatory disorders.

TRIAL REGISTRATION: ClinicalTrials.gov, NCT01067742, registered on February 12, 2010.}, } @article {pmid31874637, year = {2019}, author = {Nguyen, QH and Nguyen-Vo, TH and Le, NQK and Do, TTT and Rahardja, S and Nguyen, BP}, title = {iEnhancer-ECNN: identifying enhancers and their strength using ensembles of convolutional neural networks.}, journal = {BMC genomics}, volume = {20}, number = {Suppl 9}, pages = {951}, pmid = {31874637}, issn = {1471-2164}, mesh = {*Enhancer Elements, Genetic ; *Neural Networks, Computer ; Sequence Analysis, DNA/*methods ; }, abstract = {BACKGROUND: Enhancers are non-coding DNA fragments which are crucial in gene regulation (e.g. transcription and translation). Having high locational variation and free scattering in 98% of non-encoding genomes, enhancer identification is, therefore, more complicated than other genetic factors. To address this biological issue, several in silico studies have been done to identify and classify enhancer sequences among a myriad of DNA sequences using computational advances. Although recent studies have come up with improved performance, shortfalls in these learning models still remain. To overcome limitations of existing learning models, we introduce iEnhancer-ECNN, an efficient prediction framework using one-hot encoding and k-mers for data transformation and ensembles of convolutional neural networks for model construction, to identify enhancers and classify their strength. The benchmark dataset from Liu et al.'s study was used to develop and evaluate the ensemble models. A comparative analysis between iEnhancer-ECNN and existing state-of-the-art methods was done to fairly assess the model performance.

RESULTS: Our experimental results demonstrates that iEnhancer-ECNN has better performance compared to other state-of-the-art methods using the same dataset. The accuracy of the ensemble model for enhancer identification (layer 1) and enhancer classification (layer 2) are 0.769 and 0.678, respectively. Compared to other related studies, improvements in the Area Under the Receiver Operating Characteristic Curve (AUC), sensitivity, and Matthews's correlation coefficient (MCC) of our models are remarkable, especially for the model of layer 2 with about 11.0%, 46.5%, and 65.0%, respectively.

CONCLUSIONS: iEnhancer-ECNN outperforms other previously proposed methods with significant improvement in most of the evaluation metrics. Strong growths in the MCC of both layers are highly meaningful in assuring the stability of our models.}, } @article {pmid31858403, year = {2020}, author = {Cho, Y and Choi, YI and Oh, S and Han, J and Joo, SK and Lee, DH and Jung, YJ and Kim, BG and Lee, KL and Kim, W}, title = {Point shear wave elastography predicts fibrosis severity and steatohepatitis in alcohol-related liver disease.}, journal = {Hepatology international}, volume = {14}, number = {2}, pages = {270-280}, pmid = {31858403}, issn = {1936-0541}, support = {03-2019-2//Seoul Metropolitan Government Seoul National University (SMG-SNU) Boramae Medical Center Fund/ ; }, mesh = {Elasticity Imaging Techniques ; Female ; Humans ; Liver Cirrhosis, Alcoholic/*diagnostic imaging/pathology ; Male ; Middle Aged ; Predictive Value of Tests ; Prospective Studies ; Severity of Illness Index ; }, abstract = {BACKGROUND: Point shear wave elastography (pSWE) is a convenient noninvasive tool for assessing liver fibrosis in chronic liver disease. However, there is little information on the correlation between pSWE and the histological findings of alcohol-related liver disease (ALD). Thus, we investigated the diagnostic performance of pSWE in discriminating the fibrosis stage of patients with ALD.

METHODS: A total of 251 Korean patients with ALD were prospectively enrolled. The diagnostic performance of pSWE was evaluated on the basis of histological fibrosis severity according to Kleiner/Brunt et al.'s criteria and the Laennec classification.

RESULTS: Median liver stiffness on pSWE significantly increased as liver fibrosis stage increased (p < 0.001). Liver stiffness measurement proved to be an excellent diagnostic indicator in the evaluation of a ≥ F2 stage (area under the receiver operating characteristics curve [AUROC] 0.93; cutoff > 1.46 m/s), ≥ F3 stage (AUROC 0.90; cutoff > 1.47 m/s), and F4 stage (AUROC 0.91; cutoff > 1.66 m/s). Compared with noninvasive serum fibrosis tests, pSWE had the highest AUROC for predicting ≥ F2, ≥ F3, and = F4 stages and the highest Obuchowski index (0.931 ± 0.007; all p < 0.001). The AUROC for discriminating steatohepatitis from simple steatosis was 0.93 (> 1.49 m/s) and the AUROC for discriminating cirrhosis with steatohepatitis from cirrhosis without steatohepatitis was 0.92 (> 2.52 m/s).

CONCLUSION: pSWE not only gives an accurate indication of liver fibrosis stage in ALD, but also can allow patients with severe alcoholic steatohepatitis to begin corticosteroid treatment without exposing them to the risks of liver biopsy.

CLINICAL TRIAL REGISTRATION: Clincialtrials.gov Identifier NCT01943318.}, } @article {pmid31838847, year = {2020}, author = {Tadmor, R and Tang, S and Yao, CW and Gulec, S and Yadav, S}, title = {Comment on "Comparison of the Lateral Retention Forces on Sessile, Pendant, and Inverted Sessile Drops".}, journal = {Langmuir : the ACS journal of surfaces and colloids}, volume = {36}, number = {1}, pages = {475-476}, doi = {10.1021/acs.langmuir.9b02660}, pmid = {31838847}, issn = {1520-5827}, abstract = {Tadmor et al.'s 2009 PRL article shows experiments of pendant drops with ∼30% higher retention forces than their sessile analogues. A recent article (de la Madrid, R. et al. Langmuir 2019, 35, 2871) seemingly explains this result theoretically using a drastically different experimental system that shows a ∼3% higher force that exceeds the scatter in three out of four data points. The differences between the two experimental systems might have allowed the two theories to coexist, but Tadmor's theory, which can explain both, allows an understanding of the solid-liquid interaction, which the newer theory lacks.}, } @article {pmid31831758, year = {2019}, author = {Lebedev, MA and Ossadtchi, A and Mill, NA and Urpí, NA and Cervera, MR and Nicolelis, MAL}, title = {Analysis of neuronal ensemble activity reveals the pitfalls and shortcomings of rotation dynamics.}, journal = {Scientific reports}, volume = {9}, number = {1}, pages = {18978}, pmid = {31831758}, issn = {2045-2322}, support = {DP1 OD006798/OD/NIH HHS/United States ; R01 NS073952/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; *Computer Simulation ; Haplorhini ; *Models, Neurological ; Motor Cortex/cytology/*physiology ; Neurons/cytology/*physiology ; }, abstract = {Back in 2012, Churchland and his colleagues proposed that "rotational dynamics", uncovered through linear transformations of multidimensional neuronal data, represent a fundamental type of neuronal population processing in a variety of organisms, from the isolated leech central nervous system to the primate motor cortex. Here, we evaluated this claim using Churchland's own data and simple simulations of neuronal responses. We observed that rotational patterns occurred in neuronal populations when (1) there was a temporal sequence in peak firing rates exhibited by individual neurons, and (2) this sequence remained consistent across different experimental conditions. Provided that such a temporal order of peak firing rates existed, rotational patterns could be easily obtained using a rather arbitrary computer simulation of neural activity; modeling of any realistic properties of motor cortical responses was not needed. Additionally, arbitrary traces, such as Lissajous curves, could be easily obtained from Churchland's data with multiple linear regression. While these observations suggest that temporal sequences of neuronal responses could be visualized as rotations with various methods, we express doubt about Churchland et al.'s bold assessment that such rotations are related to "an unexpected yet surprisingly simple structure in the population response", which "explains many of the confusing features of individual neural responses". Instead, we argue that their approach provides little, if any, insight on the underlying neuronal mechanisms employed by neuronal ensembles to encode motor behaviors in any species.}, } @article {pmid31829720, year = {2021}, author = {Lopez, LD and Moorman, K and Schneider, S and Baker, MN and Holbrook, C}, title = {Morality is relative: Anger, disgust, and aggression as contingent responses to sibling versus acquaintance harm.}, journal = {Emotion (Washington, D.C.)}, volume = {21}, number = {2}, pages = {376-390}, doi = {10.1037/emo0000707}, pmid = {31829720}, issn = {1931-1516}, mesh = {Adult ; Aggression/*psychology ; Anger/*physiology ; *Disgust ; Emotions/physiology ; Female ; Friends/*psychology ; Humans ; Male ; *Morals ; Siblings/*psychology ; *Social Behavior ; }, abstract = {Angry reactions to moral violations should be heightened when wrongs befall oneself in comparison with when wrongs befall acquaintances, as prior research by Molho, Tybur, Güler, Balliet, and Hofmann (2017) demonstrates, because aggressive confrontation is inherently risky and therefore only incentivized by natural selection to curtail significant fitness costs. Here, in 3 preregistered studies, we extend this sociofunctional perspective to cases of wrongs inflicted on siblings. We observed equivalently heightened anger in response to transgressions against either oneself or one's sibling relative to transgressions against acquaintances across studies, whereas transgressions against acquaintances evoked greater disgust and/or fear (both associated with social avoidance) in 2 of the 3 studies. Studies 2 and 3, which incorporated measures of tendencies to confront the transgressor, confirmed that the elevated anger elicited by self or sibling harm partially mediated heightened inclinations toward direct aggression. Finally, in Study 3 we compared tendencies to experience anger and to directly aggress on behalf of siblings and close friends. Despite reporting greater affiliative closeness for friends than for siblings, harm to friends failed to evoke heightened anger relative to acquaintance harm, and participants were inclined to directly aggress against those who had harmed their sibling to a significantly greater extent than when the harm befell their friend. These overall results broadly replicate Molho et al.'s (2017) findings and theoretically extend the sociofunctionalist account of moral emotions to kinship. (PsycInfo Database Record (c) 2021 APA, all rights reserved).}, } @article {pmid31821943, year = {2020}, author = {Hendricks, JH and Neumann, C}, title = {A Bayesian approach for the analysis of error rate studies in forensic science.}, journal = {Forensic science international}, volume = {306}, number = {}, pages = {110047}, doi = {10.1016/j.forsciint.2019.110047}, pmid = {31821943}, issn = {1872-6283}, abstract = {Over the past decade, the field of forensic science has received recommendations from the National Research Council of the U.S. National Academy of Sciences, the U.S. National Institute of Standards and Technology, and the U.S. President's Council of Advisors on Science and Technology to study the validity and reliability of forensic analyses. More specifically, these committees recommend estimation of the rates of occurrence of erroneous conclusions drawn from forensic analyses. "Black box" studies for the various subjective feature-based comparison methods are intended for this purpose. In general, "black box" studies often have unbalanced designs, comparisons that are not independent, and missing data. These aspects pose difficulty in the analysis of the results and are often ignored. Instead, interpretation of the data relies on methods that assume independence between observations and a balanced experiment. Furthermore, all of these projects are interpreted within the frequentist framework and result in point estimates associated with confidence intervals that are confusing to communicate and understand. We propose to use an existing likelihood-free Bayesian inference method, called Approximate Bayesian Computation (ABC), that is capable of handling unbalanced designs, dependencies among the observations, and missing data. ABC allows for studying the parameters of interest without recourse to incoherent and misleading measures of uncertainty such as confidence intervals. By taking into account information from all decision categories for a given examiner and information from the population of examiners, our method also allows for quantifying the risk of error for the given examiner, even when no error has been recorded for that examiner. This opens the door to the detection of behavioural patterns in the decision-making of examiners through their ABC rate estimates. These patterns could be used to detect error prone examiners, enabling additional training efforts to be more tailored to each examiner, limiting the risk of errors before they occur. We illustrate our proposed method by reanalysing the results of the "Noblis Black Box" study by Ulery et al. [18]. We did not choose this study because we disagree with their results, but because it is a good example of a study with dependent observations and missing data, and the data is publicly available. The ABC estimates for the population generally agreed with Ulery et al.'s plug-in estimates. However, credible intervals obtained from ABC are much wider than the confidence intervals for the corresponding parameter estimates that did not account for the dependencies among observations.}, } @article {pmid31809695, year = {2020}, author = {Stelwagen, MA and van Kempen, AAMW and Westmaas, A and Blees, YJ and Scheele, F}, title = {Integration of Maternity and Neonatal Care to Empower Parents.}, journal = {Journal of obstetric, gynecologic, and neonatal nursing : JOGNN}, volume = {49}, number = {1}, pages = {65-77}, doi = {10.1016/j.jogn.2019.11.003}, pmid = {31809695}, issn = {1552-6909}, mesh = {Female ; Humans ; Infant, Newborn ; Male ; Maternal-Child Health Services/*standards/trends ; Parents/education/*psychology ; *Patient Participation ; Pregnancy ; }, abstract = {OBJECTIVE: To describe the transition from a traditional hospital design with separate maternity and neonatal departments to a design in which maternity and neonatal health care infrastructures are integrated to empower parents.

DESIGN: A descriptive, qualitative analysis.

SETTING: A mother and child center in a teaching hospital in Amsterdam.

PARTICIPANTS: Six staff members who were involved in the transition.

METHODS: We analyzed the content of all relevant policy reports and other related documents that were produced during the transition from April 2010 to October 2014. This content was supplemented with in-depth, semistructured interviews with the six participants. We used thematic analysis and Bravo et al.'s model of patient empowerment to analyze the documents and the qualitative interview data.

RESULTS: We identified eight themes. At the health care system level, the four themes were Joint Vision and Goal, Integration of Three Wards Into One With Single-Family Rooms, Reorganization of the Health Care Team, and New Equipment. At the health care provider level, the three themes were Training for Extension of Professional Goals, Intensified Coaching for Parents, and Implementing Patient Centeredness. The single theme at the patient level was Opinions and Experiences of Parents.

CONCLUSION: We found a good fit between the new design and Bravo et al.'s model of patient empowerment. Challenges that remain include the adaptation of staff training programs and further development of the infrastructure in collaboration with staff and parents. The experiences of parents and staff members will be evaluated in future studies.}, } @article {pmid31806037, year = {2019}, author = {Presseau, J and McCleary, N and Lorencatto, F and Patey, AM and Grimshaw, JM and Francis, JJ}, title = {Action, actor, context, target, time (AACTT): a framework for specifying behaviour.}, journal = {Implementation science : IS}, volume = {14}, number = {1}, pages = {102}, pmid = {31806037}, issn = {1748-5908}, support = {//CIHR/Canada ; }, mesh = {Clinical Competence/*standards ; Guideline Adherence/*standards ; Health Personnel/*standards ; Health Plan Implementation/*methods ; Health Services Research/*methods ; Humans ; Models, Theoretical ; *Quality Improvement ; Time ; }, abstract = {BACKGROUND: Designing implementation interventions to change the behaviour of healthcare providers and other professionals in the health system requires detailed specification of the behaviour(s) targeted for change to ensure alignment between intervention components and measured outcomes. Detailed behaviour specification can help to clarify evidence-practice gaps, clarify who needs to do what differently, identify modifiable barriers and enablers, design interventions to address these and ultimately provides an indicator of what to measure to evaluate an intervention's effect on behaviour change. An existing behaviour specification framework proposes four domains (Target, Action, Context, Time; TACT), but insufficiently clarifies who is performing the behaviour (i.e. the Actor). Specifying the Actor is especially important in healthcare settings characterised by multiple behaviours performed by multiple different people. We propose and describe an extension and re-ordering of TACT to enhance its utility to implementation intervention designers, practitioners and trialists: the Action, Actor, Context, Target, Time (AACTT) framework. We aim to demonstrate its application across key steps of implementation research and to provide tools for its use in practice to clarify the behaviours of stakeholders across multiple levels of the healthcare system.

METHODS AND RESULTS: We used French et al.'s four-step implementation process model to describe the potential applications of the AACTT framework for (a) clarifying who needs to do what differently, (b) identifying barriers and enablers, (c) selecting fit-for-purpose intervention strategies and components and (d) evaluating implementation interventions.

CONCLUSIONS: Describing and detailing behaviour using the AACTT framework may help to enhance measurement of theoretical constructs, inform development of topic guides and questionnaires, enhance the design of implementation interventions and clarify outcome measurement for evaluating implementation interventions.}, } @article {pmid31779551, year = {2019}, author = {Woods, S}, title = {Commentary 1: The Role of Ethical Reflexivity in Conducting Ethically Challenging Qualitative Research.}, journal = {Journal of empirical research on human research ethics : JERHRE}, volume = {14}, number = {5}, pages = {462-465}, doi = {10.1177/1556264619857856a}, pmid = {31779551}, issn = {1556-2654}, mesh = {Child ; Decision Making ; *Ethics, Research ; Humans ; Qualitative Research ; *Research Personnel ; }, abstract = {This paper is a commentary on Herzog et al.'s vignette drawn from their experience of conducting ethically challenging qualitative research. They describe an encounter with a family in which an older child has acted as a sibling donor to a sick younger sibling. It is evident that the process has taken its toll on the well-being of the older child and has created tensions within the family. What then are the ethical boundaries and responsibilities of researchers who enter the private domain of the family? This commentary responds with a model of "ethical reflexivity" which shows how a reflexive researcher can incorporate moral reflection at the different stages of the research process. Reflexivity works differently at different points, upstream it allows for anticipation and planning, incorporating ethical strategies into the methodology. Midstream reflexivity allows for evaluation, reflection and strategic response as the research unfolds and downstream it allows for a critical evaluation of how the research played out. Although it is a vital resource for any society to allow a wide degree of freedom for social scientists to research the social life, this freedom also brings responsibilities. Participation in research both creates and reveals the vulnerabilities of participants and since the researcher is entangled in these complexities they must also be prepared to respond and act. At times it may be necessary to step out of the role of researcher in order to offer support or take more decisive action especially when the well-being of vulnerable participants is at stake.}, } @article {pmid31779548, year = {2019}, author = {Pellicano, E and Stears, M}, title = {Commentary 1: Weksler-Derri et al.'s "Ethical Challenges in Participatory Research with Autistic Adults in Israel".}, journal = {Journal of empirical research on human research ethics : JERHRE}, volume = {14}, number = {5}, pages = {452-454}, doi = {10.1177/1556264619858524a}, pmid = {31779548}, issn = {1556-2654}, mesh = {Adult ; *Autistic Disorder ; Humans ; Israel ; Morals ; }, } @article {pmid31779156, year = {2019}, author = {Stanistreet, D and Hyseni, L and Puzzolo, E and Higgerson, J and Ronzi, S and Anderson de Cuevas, R and Adekoje, O and Bruce, N and Mbatchou Ngahane, B and Pope, D}, title = {Barriers and Facilitators to the Adoption and Sustained Use of Cleaner Fuels in Southwest Cameroon: Situating 'Lay' Knowledge within Evidence-Based Policy and Practice.}, journal = {International journal of environmental research and public health}, volume = {16}, number = {23}, pages = {}, pmid = {31779156}, issn = {1660-4601}, mesh = {Adult ; Air Pollution, Indoor/*prevention & control ; Cameroon ; Cooking/*methods ; Family Characteristics ; Focus Groups ; Health Knowledge, Attitudes, Practice ; Humans ; Policy ; Qualitative Research ; }, abstract = {Approximately four million people die each year in low- and middle-income countries from household air pollution (HAP) due to inefficient cooking with solid fuels. Liquid Petroleum Gas (LPG) offers a clean energy option in the transition towards renewable energy. This qualitative study explored lay knowledge of barriers and facilitators to scaling up clean fuels in Cameroon, informed by Quinn et al.'s Logic Model. The model has five domains and we focused on the user and community needs domain, reporting the findings of 28 semi-structured interviews (SSIs) and four focus group discussions (FGDs) that explored the reasons behind fuel use choices. The findings suggest that affordability, safety, convenience, and awareness of health issues are all important influences on decision making to the adoption and sustained use of LPG, with affordability being the most critical issue. We also found the ability of clean fuels to meet cooking needs to be central to decision-making, rather than an aspect of convenience, as the logic model suggests. Local communities provide important insights into the barriers and facilitators to using clean fuels. We adapt Quinn et al.'s logic model accordingly, giving more weight to lay knowledge so that it is better positioned to inform policy development.}, } @article {pmid31762956, year = {2019}, author = {Nijenhuis, ERS and van der Hart, O and Schlumpf, YR and Vissia, EM and Reinders, AATS}, title = {Considerations regarding treatment efficiency, dissociative parts and dissociative amnesia for Huntjens et al.'s Schema Therapy for Dissociative Identity Disorder.}, journal = {European journal of psychotraumatology}, volume = {10}, number = {1}, pages = {1687081}, pmid = {31762956}, issn = {2000-8066}, } @article {pmid31758203, year = {2020}, author = {Chen, J and McCulloch, A and Kim, H and Kim, T and Rhee, J and Verwey, WB and Buchanan, JJ and Wright, DL}, title = {Application of anodal tDCS at primary motor cortex immediately after practice of a motor sequence does not improve offline gain.}, journal = {Experimental brain research}, volume = {238}, number = {1}, pages = {29-37}, pmid = {31758203}, issn = {1432-1106}, mesh = {Adult ; Female ; Humans ; Male ; Motor Activity/*physiology ; Motor Cortex/*physiology ; Placebos ; *Practice, Psychological ; Psychomotor Performance/*physiology ; Serial Learning/*physiology ; *Transcranial Direct Current Stimulation ; Young Adult ; }, abstract = {Tecchio et al. (J Neurophysiology 104: 1134-1140, 2010) reported that the application of anodal tDCS at primary motor cortex (M1) immediately after practice of a procedural motor skill enhanced consolidation, which in turn improved offline gain. Tecchio et al. noted, however, that this study did not account for known after-effects associated with this form of non-invasive stimulation. The present study was designed to explicitly reevaluate Tecchio et al.'s claim. As in the original study, individuals experienced either anodal or sham stimulation at M1 after practice of a serial reaction time task (SRTT) followed by test trials 15-min later. Two additional novel conditions experienced the test trials after 120-min rather than 15-min thus allowing potential stimulation after-effects to dissipate. The expectation was that if anodal stimulation influences post-practice consolidation leading to offline gain, this effect would be present not only at 15-min but also after 120-min. In agreement with the working hypothesis, findings revealed offline gain at both 15-min and the longer 2-h time period. Unexpectedly, we found no interaction between real and sham conditions. The lack of difference between Real and Sham effects weakens confidence in the potential of post-practice tDCS for consolidation enhancement, while it is more consistent with other claims that decoupling practice and anodal tDCS stimulation in time can reduce the effectiveness of exogenous stimulation for procedural skill gain.}, } @article {pmid31750571, year = {2019}, author = {Schreurs, S and Cleutjens, K and Oude Egbrink, MGA}, title = {Increasing value in research: cost evaluations in health professions education.}, journal = {Medical education}, volume = {53}, number = {12}, pages = {1171-1173}, pmid = {31750571}, issn = {1365-2923}, mesh = {Costs and Cost Analysis ; Curriculum ; *Education, Medical ; Health Occupations ; }, abstract = {The authors use Foo et al.'s discussion of the value of economic evaluations to consider how such techniques might advance the practice of selection for medical school.}, } @article {pmid31743800, year = {2020}, author = {Flores, A and López, FJ and Vervliet, B and Cobos, PL}, title = {Prospective intolerance of uncertainty is associated with maladaptive temporal distribution of avoidance responses: An extension of Flores, López, Vervliet, and Cobos (2018).}, journal = {Journal of behavior therapy and experimental psychiatry}, volume = {68}, number = {}, pages = {101527}, doi = {10.1016/j.jbtep.2019.101527}, pmid = {31743800}, issn = {1873-7943}, mesh = {Anxiety/*psychology ; Anxiety Disorders/*psychology ; *Avoidance Learning ; Female ; Humans ; Male ; Prospective Studies ; *Uncertainty ; Young Adult ; }, abstract = {BACKGROUND AND OBJECTIVES: Excessive maladaptive avoidance has been claimed to be one of the mechanisms through which intolerance of uncertainty (IU) may play its causal role in the development and maintenance of several anxiety and compulsive disorders. Consistently, Flores et al. (2018) found that individuals with higher Prospective IU (P-IU), a specific IU subfactor, display excessive avoidance response repetitions in a free-operant discriminative task to avoid an aversive noise. In the present study we tested the hypothesis that P-IU not only predicts the amount of avoidance responses but also how well the temporal distribution of such responses fits the temporal distribution of threats.

METHODS: Further correlation and hierarchical regression analysis of Flores et al.'s (2018) data served to test this hypothesis. We evaluated two aspects of the temporal distribution of responses: a) for how long participants were performing the responses; b) the behavioral discrimination between threatening and safe time periods.

RESULTS: The results showed that scoring high in P-IU was positively associated with longer periods of time dedicated to avoiding and with worse behavioral discrimination between threatening and safe time periods. Hierarchical regression analyses indicated that later addition of inhibitory intolerance of uncertainty and trait anxiety did not significantly improved the explained variance.

LIMITATIONS: Our results are exclusively based on the use of a low-cost avoidance response, and the present study does not clarify the precise mechanisms that lead high P-IU people to engage in non-optimal avoidance response distribution through time.

CONCLUSIONS: These results suggest that excessive avoidance is also driven by uncertainty of threat timing and highlight the relevance of P-IU as a vulnerability factor for excessive and outspread avoidance behaviors.}, } @article {pmid31741117, year = {2020}, author = {Coderre, TJ and Laferrière, A}, title = {The emergence of animal models of chronic pain and logistical and methodological issues concerning their use.}, journal = {Journal of neural transmission (Vienna, Austria : 1996)}, volume = {127}, number = {4}, pages = {393-406}, pmid = {31741117}, issn = {1435-1463}, support = {//CIHR/Canada ; }, mesh = {Animals ; *Chronic Pain ; *Disease Models, Animal ; Research Design/*standards ; Translational Research, Biomedical/*standards ; }, abstract = {This paper examines the development of and some logistical and methodological issues surrounding the use of animal models of chronic pain. The first section addresses the emergent move towards mechanism-based and disease-related animal models of chronic pain that has accelerated since the late 1980s following publication of Bennett and Xie's (Pain 33:87-107, 1998) paper on chronic constriction injury of the sciatic nerve and Stein et al.'s (Pharmacol Biochem Behav 31:445-451, 1988) paper on unilateral hind paw inflammation with complete Freund's adjuvant. The discussion covers vast areas of chronic pain models developed over the past 50 years, starting with the numerous neuropathic, inflammatory and central pain models, as well as the growing number of models developed to study various forms of chronic pain from chronic back pain to visceral pain. It also examines the advantages and disadvantages of tonic pain models, mechanism-based and disease-related models of chronic pain, including issues related to the novel discovery of injury- or disease-related pathophysiological processes, the expansion of testing repertoires, and the successes and failures in the translation of analgesic development from animal preclinical models to human chronic pain conditions. The second section addresses experimental design considerations in the implementation of one of the 3Rs for the use of animal models of chronic pain; that is methods employed to reduce the number of animals used. The discussion covers various issues including the advantages and disadvantages of repeated dose designs and within-group drug testing, including incremental dosing schedules, and crossover designs. It also examines concerns surrounding the stability of symptoms and measures, including varying durations of multiple symptoms and the potential development of nociceptive sensitization, as well as possible use-dependent alterations in drug sensitivity and time-dependent changes in pain processes in specific animal models.}, } @article {pmid31688115, year = {2020}, author = {Wong, A and Sbitany, H}, title = {Reconstruction of Intrapelvic Defects Using the Free Anterolateral Thigh Flap: Expanding the Traditional Algorithm.}, journal = {Annals of plastic surgery}, volume = {84}, number = {5}, pages = {554-558}, doi = {10.1097/SAP.0000000000002048}, pmid = {31688115}, issn = {1536-3708}, mesh = {Algorithms ; Female ; *Free Tissue Flaps ; Humans ; Male ; *Plastic Surgery Procedures ; Retrospective Studies ; Thigh/surgery ; }, abstract = {BACKGROUND: Reconstruction of intrapelvic soft tissue defects traditionally relies on regional pedicled myocutaneous flaps. However, there remain situations in which local options are unavailable. We review our experience treating intrapelvic defects with the anterolateral thigh (ALT) microvascular free flap.

METHODS: A retrospective, institutional review was conducted from 2014 to 2018 of patients undergoing microvascular ALT flap reconstruction of intrapelvic defects. Four patients were identified in this cohort out of 92 total pelvic reconstruction cases.

RESULTS: All patients underwent abdominoperineal resection (APR) for rectal cancer treatment. In the two male patients, pelvic abscesses and bladder leak necessitated soft tissue reconstruction after radiation and APR. In both, regional tissue options were unavailable, and a buried ALT free flap was used for soft tissue reconstruction. Both female patients developed rectovaginal fistulas secondary to their tumor burden, necessitating posterior vaginal wall resections. Prior surgical scars and ostomies made abdominal wall tissue unavailable; thus, free ALTs were used to eliminate intrapelvic dead space and reconstruct the posterior vaginal wall. In all cases, recipient vessels were the deep inferior epigastric artery and vein. Flap survival was 100%.

CONCLUSIONS: Pelvic reconstruction has traditionally been addressed with local/regional pedicled flaps. In cases where these are unavailable, the free ALT flap is a versatile option when buried for intrapelvic reconstruction or posterior vaginal wall lining. We also propose updating Cordeiro et al.'s classic vaginal defect reconstruction algorithm to include the free ALT flap for type IB cases in which the rectus abdominis is unavailable.}, } @article {pmid31683486, year = {2019}, author = {van den Noort, M and Vermeire, K and Staudte, H and Perriard, B and Bosch, P and Lim, S}, title = {The Relationship Between Linguistic Ability, Multilingualism, and Dementia.}, journal = {Journal of Alzheimer's disease : JAD}, volume = {72}, number = {4}, pages = {1041-1044}, doi = {10.3233/JAD-190807}, pmid = {31683486}, issn = {1875-8908}, mesh = {Aged ; *Alzheimer Disease ; Humans ; Language ; Linguistics ; Longitudinal Studies ; *Multilingualism ; }, abstract = {In a recent article of the Journal of Alzheimer's Disease, Hack et al. (2019) argue that linguistic ability rather than multilingualism is a significant predictor of dementia. In their longitudinal study, they investigated 325 religious sisters who were older than 75 years of age. Self-reports were used in order to determine multilingualism. They found that speaking two or three languages did not delay the onset of dementia. However, they did find that individuals speaking four or more languages were less likely to suffer from dementia than those speaking only one language and concluded that having linguistic ability was a more significant predictor of dementia than being multilingual. However, more research is needed in order to identify the characteristics of multilingualism most salient for the risk of dementia. In this commentary, we raise several important methodological and statistical issues that are likely to have affected the findings of Hack et al.'s study. As a result, although their study makes an important contribution to the research field, drawing a conclusion at this time that linguistic ability is more a predictor of dementia than multilingualism would be premature; moreover, their preliminary results cannot be generalized to the general population.}, } @article {pmid31678616, year = {2019}, author = {Tarita-Nistor, L and Samet, S and Trope, GE and González, EG}, title = {Dominance wave propagation during binocular rivalry in mild glaucoma.}, journal = {Vision research}, volume = {165}, number = {}, pages = {64-71}, doi = {10.1016/j.visres.2019.10.006}, pmid = {31678616}, issn = {1878-5646}, mesh = {Aged ; Corpus Callosum/physiopathology ; Dominance, Ocular/*physiology ; Female ; Glaucoma, Open-Angle/*physiopathology ; Humans ; Male ; Middle Aged ; Photic Stimulation/methods ; Vision, Binocular/*physiology ; Visual Fields/physiology ; Visual Pathways/physiopathology ; Visual Perception/*physiology ; }, abstract = {Glaucoma is both a progressive optic neuropathy and a neurodegenerative disease affecting structures in the primary visual pathway. Other vision-associated areas may also be affected, including the corpus callosum which is involved in inter-hemispheric transfer. This study evaluated dominance wave propagation during binocular rivalry to probe the efficacy of the inter-hemispheric transfer in 20 patients with mild open angle glaucoma and 25 age-matched controls. The two groups were matched for functional measures such as stereo-acuity, binocular visual acuity, and visual field mean deviation. Monocular functional and structural measures were equivalent for the left and right eye of each participant. Using Wilson et al.'s travelling wave paradigm [Nature, 412 (2001) 907-910], intra- and inter-hemispheric failure rates of traveling wave transmission and the travelling wave propagation times were recorded for the two groups. For the control group, the wave propagation failure rate was significantly greater for the inter- than for the intra-hemispheric condition, but for the glaucoma group, the failure rates were equally high for the two conditions. The wave propagation time was significantly longer for the inter- than for the intra-hemispheric condition for the control group, while the opposite was true for the glaucoma group. These results reveal changes in the wave dynamics of rivalry dominance in patients with mild glaucoma who otherwise have normal performance on standard functional measures.}, } @article {pmid31676968, year = {2020}, author = {Chen, P and Engel, S and Wang, C}, title = {The multivariate adaptive design for efficient estimation of the time course of perceptual adaptation.}, journal = {Behavior research methods}, volume = {52}, number = {3}, pages = {1073-1090}, doi = {10.3758/s13428-019-01301-6}, pmid = {31676968}, issn = {1554-3528}, support = {R305D160010//IES/International ; SES-1659328//NSF/International ; 31300862//NSFC/International ; R01 HD079439/HD/NICHD NIH HHS/United States ; }, mesh = {Probability ; *Research Design ; Uncertainty ; }, abstract = {In experiments on behavioral adaptation, hundreds or even thousands of trials per subject are often required in order to accurately recover the many psychometric functions that characterize adaptation's time course. More efficient methods for measuring perceptual changes over time would be beneficial to such efforts. In this article, we propose two methods to adaptively select the optimal stimuli sequentially in an experiment on adaptation: These are the minimum entropy (ME) method and the match probability (MP) method. The ME method minimizes the uncertainty about the joint posterior distribution of the function parameters at each trial and is mathematically equivalent to Zhao, Lesmes, and Lu's (2019) method, which efficiently measures time courses of perceptual change by maximizing information gain. The MP method selects the next stimulus that makes the value of the psychometric function closest to .5-that is, where the probability of choosing either one of the two options for each stimulus is closest to .5. We extended Zhao et al.'s (2019) work by evaluating the ME method in a new domain (contrast adaptation) with two simulation studies that compared it to MP and two other methods (i.e., traditional staircase and random methods), and also explored the optimal block length. ME outperformed the other three methods in general, and using fewer longer blocks generally produced better parameter recovery than using more shorter blocks.}, } @article {pmid31673225, year = {2019}, author = {Xu, C and Wu, J and Wang, J}, title = {Associations of rs524952 and rs634990 gene polymorphisms in 15q14 with high myopia: A meta-analysis.}, journal = {Molecular vision}, volume = {25}, number = {}, pages = {603-609}, pmid = {31673225}, issn = {1090-0535}, mesh = {Adult ; Chromosomes, Human, Pair 15/*genetics ; *Genetic Association Studies ; *Genetic Predisposition to Disease ; Humans ; Middle Aged ; Models, Genetic ; Myopia/*genetics ; Polymorphism, Single Nucleotide/*genetics ; Publication Bias ; Risk Factors ; Young Adult ; }, abstract = {PURPOSE: Many studies have been conducted to investigate the association between the rs524952 and rs634990 polymorphisms and high myopia (HM). However, the results were conflicting. Thus, a meta-analysis was needed to reveal the real association between the two single nucleotide polymorphisms (SNPs) and HM.

METHODS: All eligible studies published in Pubmed, Embase, China Biologic Medicine (CBM), the China National Knowledge Infrastructure (CNKI), the Cochrane Library, and the Web of Science from 2010 to March 2019 were examined.

RESULTS: Six comparison groups in four studies with 5,293 subjects for the rs524952 polymorphism and five studies with 6,750 subjects for the rs634990 polymorphism were included. No statistically significant associations were observed between the rs524952 and rs634990 polymorphisms and HM under the allelic model, recessive genetic model, and dominant genetic model in this meta-analysis. Subgroup analysis was conducted by dividing the studies into two groups according to the case sample size, which showed that the association between the rs524952 polymorphism and HM was found only in a subgroup of fewer than 300 cases under the dominant genetic model (OR=0.64; 95% confidence interval [CI]:0.43-0.96). Sensitivity analysis for the rs524952 polymorphism suggested the results of this study were stable under all the genetic models. However, the association between the rs634990 polymorphism and HM turned out to be statistically significant in the allelic, recessive, and dominant genetic models after the omission of Qiang et al.'s study. No publication bias was found.

CONCLUSIONS: The results of this meta-analysis suggested the rs524952 and rs634990 polymorphisms may have nothing to do with the development of HM. The present results must be confirmed with larger-scale studies in the future.}, } @article {pmid31671641, year = {2019}, author = {Horvat, B and Ducman, V}, title = {Potential of Green Ceramics Waste for Alkali Activated Foams.}, journal = {Materials (Basel, Switzerland)}, volume = {12}, number = {21}, pages = {}, pmid = {31671641}, issn = {1996-1944}, support = {C3330-17-529032//European Regional Development Fund AND Republic of Slovenia, Ministry of Education, Science and Sport/ ; }, abstract = {The aim of the paper is to research the influence of foaming and stabilization agents in the alkali activation process of waste green ceramics for future low cost up-cycling into lightweight porous thermal insulating material. Green waste ceramics, which is used in the present article, is a green body residue (non-successful intermediate-product) in the synthesis of technical ceramics for fuses. This residue was alkali activated with Na-water glass and NaOH in theoretically determined ratio based on data from X-ray fluorescence (XRF) and X-ray powder diffraction (XRD) that was set to maximise mechanical properties and to avoid efflorescence. Prepared mixtures were compared to alkali activated material prepared in theoretically less favourable ratios, and tested on the strength and density. Selected mixtures were further foamed with different foaming agents, that are Na-perborate (s), H2O2 (l), and Al (s), and supported by a stabilization agent, i.e., Na-dodecyl sulphate. The goal of the presented work was to prepare alkali activated foam based on green ceramics with density below 1 kg/l and compressive strength above 1 MPa.}, } @article {pmid31670540, year = {2020}, author = {Duncan, BL and Sparks, JA}, title = {When meta-analysis misleads: A critical case study of a meta-analysis of client feedback.}, journal = {Psychological services}, volume = {17}, number = {4}, pages = {487-496}, doi = {10.1037/ser0000398}, pmid = {31670540}, issn = {1939-148X}, mesh = {Biomedical Research/*standards ; *Feedback, Psychological ; Humans ; *Meta-Analysis as Topic ; *Patient Reported Outcome Measures ; Process Assessment, Health Care/*standards ; Psychotherapy/*standards ; }, abstract = {Consumers of psychotherapy outcome literature consider meta-analysis the gold standard for assessing the efficacy of interventions across disparate studies. Many assume that findings are valid, especially when published in journals with research credentials. Uncritical acceptance, however, can result in real-world consequences, including whether interventions attain evidence-based status or become marginalized or are considered for implementation in public service arenas. This article examines one meta-analysis, "The Effect of Using the Partners for Change Outcome Management System as Feedback Tool in Psychotherapy-A Systematic Review and Meta-Analysis" (Østergård, Randa, & Hougaard, 2018). The findings are at odds with both the empirical record of routine outcome management as well as professional taskforce recommendations and thus provide an ideal exemplar of the risks of uncritically accepting the conclusions of a meta-analysis. Using guidelines from the Cochrane Handbook for Systematic Reviews of Interventions (Higgins & Green, 2011) and a qualitative case study methodology, this article examines Østergård et al.'s (2018) study selection, quality of evidence, and appropriateness of interpretation, emphasizing the link between flawed method and the ultimate validity of its conclusions. The method illustrated in this case study can be used to assess the legitimacy of meta-analytic findings to inform practice, funding, and policy decisions as well as how rhetoric minimizes flaws and bolsters believability. Our analysis revealed that half of the selected studies of the meta-analysis contained significant limitations, including inadequate dose of treatment and/or adherence problems, thereby calling into question its conclusions. (PsycInfo Database Record (c) 2020 APA, all rights reserved).}, } @article {pmid31670315, year = {2019}, author = {Karim, HMR and Esquinas, AM}, title = {Saiphoklang et al.'s home mechanical ventilation in a developing country: What else can be done for an improved future program?.}, journal = {Lung India : official organ of Indian Chest Society}, volume = {36}, number = {6}, pages = {570}, pmid = {31670315}, issn = {0970-2113}, } @article {pmid31657075, year = {2020}, author = {Currier, JM and Isaak, SL and McDermott, RC}, title = {Validation of the Expressions of Moral Injury Scale-Military version-Short Form.}, journal = {Clinical psychology & psychotherapy}, volume = {27}, number = {1}, pages = {61-68}, doi = {10.1002/cpp.2407}, pmid = {31657075}, issn = {1099-0879}, mesh = {Adult ; Factor Analysis, Statistical ; Female ; Humans ; Male ; Middle Aged ; Military Personnel/*psychology/statistics & numerical data ; *Morals ; Psychometrics ; Reproducibility of Results ; Stress, Psychological/*psychology ; Surveys and Questionnaires/*standards ; United States ; Veterans/*psychology/statistics & numerical data ; Young Adult ; }, abstract = {Military personnel may encounter morally injurious events that lead to emotional, social, and spiritual suffering that transcend and/or overlap with mental health diagnoses (e.g., post-traumatic stress disorder [PTSD]). Advancement of scientific research and potential clinical innovation for moral injury (MI) requires a diversity of measurement approaches. Drawing on results from the bifactor model in Currier et al.'s (2017) psychometric evaluation of the Expressions of Moral Injury Scale-Military version (EMIS-M), this study validated a four-item short form of the instrument with two samples of veterans with a history of war-zone service. Namely, despite the reduced number of items, the EMIS-M-Short Form (SF) yielded favourable internal consistency and comparable levels of convergent validity with theoretically related constructs (e.g., PTSD and struggles with morality and ultimate meaning) as the full-length version. Notwithstanding the possible utility of distinguishing between self- and other-directed forms of MI, factor analytic results further revealed that the EMIS-M-SF was best conceptualized with a unidimensional factorial model that might allow for a general assessment of MI-related outcomes. Overall, these initial results suggest that the EMIS-M-SF may hold promise as a short, reliable, and valid assessment of overall outcomes related to a possible MI.}, } @article {pmid31654369, year = {2020}, author = {Schmitz, M and Rougier, M and Yzerbyt, V}, title = {Comment on "Quantifying the informational value of classification images": A miscomputation of the infoVal metric.}, journal = {Behavior research methods}, volume = {52}, number = {3}, pages = {1383-1386}, doi = {10.3758/s13428-019-01295-1}, pmid = {31654369}, issn = {1554-3528}, support = {1.B347.19//Fonds De La Recherche Scientifique - FNRS/International ; }, abstract = {Brinkman et al. (2019) recently introduced an innovative metric-infoVal-to assess the informational value of classification images (CIs) relative to a random distribution. Although this measure constitutes a valuable tool to distinguish random from nonrandom CIs, we identified two noteworthy discrepancies between the mathematical formalization of the infoVal metric and the authors' computation. Specifically, the computation was based on the one norm instead of the Euclidean norm, and the k constant was omitted in the denominator of the ratio that produces infoVal. Accordingly, the simulations and experimental results reported by Brinkman et al. do not build on the correct infoVal computation but on a biased index. Importantly, this discrepancy in the computation affects the statistical power and Type I and error rate of the metric. Here we clarify the nature of the discrepancies in the computation and run Brinkman et al.'s Simulation 1 anew with the correct values, to illustrate their consequences. Overall, we found that relying on the miscomputed infoVal metric can lead to misguided conclusions, and we urge researchers to use the correct values.}, } @article {pmid31652457, year = {2019}, author = {Xiao, L and Zeng, F and Deng, G}, title = {Commentary on: Nomograms based on inflammatory biomarkers for predicting tumor grade and microvascular invasion in stage I/II hepatocellular carcinoma.}, journal = {Bioscience reports}, volume = {39}, number = {10}, pages = {}, pmid = {31652457}, issn = {1573-4935}, mesh = {Biomarkers, Tumor ; *Carcinoma, Hepatocellular ; Humans ; *Liver Neoplasms ; Neutrophils ; Nomograms ; }, abstract = {Some doubts were generated during the reading of nomograms based on inflammatory biomarkers for preoperatively predicting tumor grade and microvascular invasion in stage I/II hepatocellular carcinoma (HCC). We would like to highlight and discuss with authors. First, neutrophil-lymphocyte ratio (NLR) and derived NLR (dNLR) should not be entered into multivariate analysis simultaneously. Second, authors should clarify how the cutoffs of these variables including lymphocyte-monocyte ratio (LMR), dNLR, age and tumor size were set. We insist that the type of variables should be consistent when we carry out the analysis and establish the nomogram. Last, we have to point out that Li et al.'s (Biosci. Rep. (2018), 38) study failed to validate nomograms using an independent dataset.}, } @article {pmid31642091, year = {2020}, author = {Leeman, J and Toles, M}, title = {What does it take to scale-up a complex intervention? Lessons learned from the Connect-Home transitional care intervention.}, journal = {Journal of advanced nursing}, volume = {76}, number = {1}, pages = {387-397}, doi = {10.1111/jan.14239}, pmid = {31642091}, issn = {1365-2648}, support = {//Harry and Jeannette Weinberg Foundation provided to Lutheran Services in America/ ; }, mesh = {Feasibility Studies ; Home Care Services/*organization & administration ; Humans ; Program Development ; Qualitative Research ; *Transitional Care ; }, abstract = {AIMS: To discuss the multiple phases of research done to plan for wide-scale implementation (i.e. scale-up) of Connect-Home, a complex nurse-develop intervention. Barker et al.'s (Implementation Science, 2016, 11, 12) framework for intervention scale-up is applied to address the methods used to answer the following four questions: 'Who' needs to be involved in scale-up? 'What' intervention and implementation strategies need to be taken to scale? 'How' will scale-up be achieved? And what contextual factors influence 'when' scale-up is or is not successful?

DESIGN: Discussion paper.

DATA SOURCES: Data sources include the experience of our research team, supported by literature and theory. The Connect-Home team conducted multiple research studies to plan for Connect-Home scale-up. Early studies (2008-2015) focused on formative work to design the Connect-Home intervention. Recent studies have involved successive pilot tests of Connect-Home's effectiveness, implementation, and scale-up (2015-2019).

IMPLICATIONS FOR NURSING: This article describes a systematic approach that nurse researchers can apply to plan for taking their interventions to scale.

CONCLUSIONS: Planning for scale-up early in the process of intervention development is essential to speeding the translation of effective interventions into wide-scale practice.

IMPACT: This article details the methods that nursing researchers applied to develop and test the strategies needed to plan for taking a complex intervention to scale across multiple settings. The methods described are applicable to nursing and other health researchers' development and scale-up of any complex intervention.}, } @article {pmid31638413, year = {2020}, author = {Chen, ZZ and Ueta, S and Li, J and Wang, L}, title = {Computing a Consensus Phylogeny via Leaf Removal.}, journal = {Journal of computational biology : a journal of computational molecular cell biology}, volume = {27}, number = {2}, pages = {175-188}, doi = {10.1089/cmb.2019.0269}, pmid = {31638413}, issn = {1557-8666}, abstract = {Given a set [Formula: see text]. of phylogenetic trees with the same leaf-label set X, we wish to remove some leaves from the trees so that there is a tree T with leaf-label set X displaying all the resulting trees. Note that the labels of leaves removed from one input tree may be different from those of leaves removed from another input tree. One objective is to minimize the total number of leaves removed from the trees, whereas the other is to minimize the maximum number of leaves removed from an input tree. Chauve et al. refer to the problem with the first (respectively, second) objective as AST-LR (respectively, AST-LR-d), and they show that both problems are NP-hard, where NP is the class of problems solvable in non-deterministic polynomial time. They further present algorithms for the parameterized versions of both problems. In this article, we point out that their algorithm for the parameterized version of AST-LR is flawed and present a new algorithm. Since neither Chauve et al.'s algorithm for AST-LR-d nor our new algorithm for AST-LR looks practical, we further design integer-linear programming (ILP for short) models for AST-LR and AST-LR-d, and we discuss speedup issues when using popular ILP solvers (say, GUROBI or CPLEX) to solve the models. Our experimental results show that our ILP approach is quite efficient.}, } @article {pmid31612644, year = {2020}, author = {Peters, H and Sadaula, A and Masters, N and Sainsbury, A}, title = {Risks from disease caused by Mycobacterium orygis as a consequence of Greater one-horned Rhinoceros (Rhinoceros unicornis) translocation in Nepal.}, journal = {Transboundary and emerging diseases}, volume = {67}, number = {2}, pages = {711-723}, doi = {10.1111/tbed.13389}, pmid = {31612644}, issn = {1865-1682}, mesh = {Animals ; Conservation of Natural Resources ; Female ; Male ; Mycobacterium/*isolation & purification ; Mycobacterium Infections/*epidemiology/virology ; Nepal/epidemiology ; Parks, Recreational ; Perissodactyla/*microbiology ; Retrospective Studies ; Risk ; }, abstract = {The greater one-horned rhinoceros (Rhinoceros unicornis) is listed as vulnerable by the IUCN Red List. Mycobacterium orygis-associated disease was identified in a single greater one-horned rhino in Chitwan National Park in February 2015 prior to a planned translocation of five greater one-horned rhinoceros from Chitwan National Park to Bardia National Park for conservation purposes. This paper describes a qualitative disease risk analysis conducted retrospectively post-translocation for Mycobacterium orygis and this translocation, with the aim to improve the understanding of disease threats to the conservation of greater one-horned rhino. The disease risk analysis method used was devised by Sainsbury & Vaughan-Higgins (Conservation Biology, 26, 2017, 442) with modifications by Bobadilla Suarez et al (EcoHealth, 14, 2017, 1) and Rideout et al (EcoHealth, 14, 2017, 42) and included the use of a scenario tree and an analysis of uncertainty as recommended by Murray et al. (Handbook on import risk analysis for animals and animal products. Volume 1. Introduction and qualitative risk analysis, 2004), and the first time this combination of methods has been used to assess the risk from disease in a conservation translocation. The scenario tree and analysis of uncertainty increased the clarity and transparency of the analysis. Rideout et al.'s (EcoHealth, 14, 2017, 42) criteria were used to assess the source hazard and may be useful in comparative assessment of source hazards for future conservation translocations. The likelihood of release into the destination site of Mycobacterium orygis as a source hazard was estimated as of low risk, the risk of exposure of populations at the destination was of high risk and the likelihood of biological and environmental consequences was low. Overall, the risk from disease associated with Mycobacterium orygis as a result of this translocation was found to be low. Recommendations on disease risk management strategies could be improved with a better understanding of the epidemiology including the presence/absence of Mycobacterium orygis in greater one-horned rhino to develop effective disease risk management strategies.}, } @article {pmid31610740, year = {2020}, author = {Zuckerman, M and Li, C and Lin, S and Hall, JA}, title = {The Negative Intelligence-Religiosity Relation: New and Confirming Evidence.}, journal = {Personality & social psychology bulletin}, volume = {46}, number = {6}, pages = {856-868}, doi = {10.1177/0146167219879122}, pmid = {31610740}, issn = {1552-7433}, mesh = {Adult ; Cognition ; Educational Status ; Female ; Humans ; *Intelligence ; Male ; *Religion ; }, abstract = {Zuckerman et al. (2013) conducted a meta-analysis of 63 studies that showed a negative intelligence-religiosity relation (IRR). As more studies have become available and because some of Zuckerman et al.'s (2013) conclusions have been challenged, we conducted a new meta-analysis with an updated data set of 83 studies. Confirming previous conclusions, the new analysis showed that the correlation between intelligence and religious beliefs in college and noncollege samples ranged from -.20 to -.23. There was no support for mediation of the IRR by education but there was support for partial mediation by analytic cognitive style. Thus, one possible interpretation for the IRR is that intelligent people are more likely to use analytic style (i.e., approach problems more rationally). An alternative (and less interesting) reason for the mediation is that tests of both intelligence and analytic style assess cognitive ability. Additional empirical and theoretical work is needed to resolve this issue.}, } @article {pmid31591937, year = {2019}, author = {Robbins, TW}, title = {Commentary on Bechara et al.'s "A Neurobehavioral Approach to Addiction: Implications for the Opioid Epidemic and the Psychology of Addiction".}, journal = {Psychological science in the public interest : a journal of the American Psychological Society}, volume = {20}, number = {2}, pages = {91-95}, doi = {10.1177/1529100619862034}, pmid = {31591937}, issn = {2160-0031}, mesh = {Analgesics, Opioid ; *Behavior, Addictive ; *Epidemics ; Humans ; *Opioid-Related Disorders ; }, } @article {pmid31591653, year = {2019}, author = {Qiao, H and Dong, X and Shen, Y}, title = {Authenticated Key Agreement Scheme with Strong Anonymity for Multi-Server Environment in TMIS.}, journal = {Journal of medical systems}, volume = {43}, number = {11}, pages = {321}, pmid = {31591653}, issn = {1573-689X}, support = {2017YFB1400704//the National Key Research and Development Plan of China/ ; U1536202//the Natural Science Foundation of China/ ; }, mesh = {Computer Security/*standards ; Confidentiality/*standards ; Health Smart Cards ; Humans ; Information Systems/organization & administration ; Internet of Things/organization & administration ; Telemedicine/*methods/standards ; }, abstract = {The technology of Internet of Things (IoT) has appealed to both professionals and the general public to its convenience and flexibility. As a crucial application of IoT, telecare medicine information system (TMIS) provides people a high quality of life and advanced level of medical service. In TMIS, smart card-based authenticated key agreement schemes for multi-server architectures have gathered momentum and positive impetus due to the conventional bound of a single server. However, we demonstrate that most of the protocols in the literatures can not implement strong security features in TMIS, such as Lee et al.'s and Shu's scheme. They store the identity information directly, which fail to provide strong anonymity and suffer from password guessing attack. Then we propose an extended authenticated key agreement scheme (short for AKAS) with strong anonymity for multi-server environment in TMIS, by enhancing the security of the correlation parameters stored in the smart cards and calculating patients' dynamic identities. Furthermore, the proposed chaotic map-based scheme provides privacy protection and is formally proved under Burrows-Abadi-Needham (BAN) logic. At the same, the informal security analysis attests that the AKAS scheme not only could resist the multifarious security attacks but also improve efficiency by 21% compared with Lee et al.'s and Shu's scheme.}, } @article {pmid31591617, year = {2019}, author = {Guo, Y and Zhang, S and Wei, B and Legut, D and Germann, TC and Zhang, H and Zhang, R}, title = {A generalized solid strengthening rule for biocompatible Zn-based alloys, a comparison with Mg-based alloys.}, journal = {Physical chemistry chemical physics : PCCP}, volume = {21}, number = {40}, pages = {22629-22638}, doi = {10.1039/c9cp04106k}, pmid = {31591617}, issn = {1463-9084}, abstract = {Solid solution strengthening has been widely used in designing various high-performance biocompatible Mg-based alloys, but its transferability to other biocompatible metals such as Zn-based alloys is questionable or nearly absent. In the present study, an ab initio informed Peierls-Nabarro model and Leyson et al.'s strengthening model are used for a systematic investigation on solute strengthening in Zn-based alloys, which is compared with the widely studied Mg-based alloys. Although an inverse relationship was revealed between volume misfit εb and chemical misfit εSFE for both Zn-based and Mg-based alloys, most solutes would however result in positive εb and negative εSFE for Zn-based alloys, differing from Mg-based alloys. With εb and εSFE as two key descriptors, a generalized scaling diagram is finally drawn for a fast evaluation of solid solution strengthening in Zn-based alloys, indicating that the alkaline-earth and rare earth elements are better strengtheners for Zn-based alloys, which provides a general rule in designing novel biocompatible materials.}, } @article {pmid31587501, year = {2019}, author = {McShane, M and Bringsjord, S and Hendler, J and Nirenburg, S and Sun, R}, title = {A Response to Núñez et al.'s (2019) "What Happened to Cognitive Science?".}, journal = {Topics in cognitive science}, volume = {11}, number = {4}, pages = {914-917}, doi = {10.1111/tops.12458}, pmid = {31587501}, issn = {1756-8765}, mesh = {*Cognitive Science ; }, abstract = {Núñez et al.'s (2019) negative assessment of the field of cognitive science derives from evaluation criteria that fail to reflect the true nature of the field. In reality, the field is thriving on both the research and educational fronts, and it shows great promise for the future.}, } @article {pmid31584059, year = {2019}, author = {Chu, TC and Buras, ZJ and Smith, MC and Uwagwu, AB and Green, WH}, title = {From benzene to naphthalene: direct measurement of reactions and intermediates of phenyl radicals and acetylene.}, journal = {Physical chemistry chemical physics : PCCP}, volume = {21}, number = {40}, pages = {22248-22258}, doi = {10.1039/c9cp04554f}, pmid = {31584059}, issn = {1463-9084}, abstract = {Hydrogen-abstraction-C2H2-addition (HACA) is one of the most important pathways leading to the formation of naphthalene, the simplest two-ring polycyclic aromatic hydrocarbon (PAH). The major reaction channels for naphthalene formation have previously been calculated by Mebel et al., but few experiments exist to validate the theoretical predictions. In this work, time-resolved molecular beam mass spectrometry (MBMS) was used to investigate the time-dependent product formation in the reaction of a phenyl radical with C2H2 for the first time, at temperatures of 600 and 700 K and pressures of 10 and 50 Torr. A pressure-dependent model was developed with rate parameters derived from Mebel et al.'s calculations and from newly calculated pathways on the C8H7 PES at the G3(MP2,CC)//B3LYP/6-311G** level of theory. The model prediction is consistent with the MBMS product profiles at a mass-to-charge ratio (m/z) of 102 (corresponding to the H-loss product from C8H7, phenylacetylene), 103 (the initial C8H7 adduct and its isomers plus the [13]C isotopologue of phenylacetylene), 128 (naphthalene), and 129 (C10H9 isomers plus the [13]C isotopologue of naphthalene). An additional C8H7 isomer, bicyclo[4.2.0]octa-1,3,5-trien-7-yl, not considered by Mebel et al.'s calculations, contributes significantly to the signal at m/z 103 due to its stable energy and low reactivity. At high C2H2 concentrations, bimolecular reactions dominated the observed chemistry, and the m/z 128 and m/z 102 MBMS signal ratio was measured to directly determine the product branching ratio. At 600 K and 10 Torr, branching to the H-loss product (phenylacetylene) on the C8H7 PES accounted for 7.9% of phenyl radical consumption, increasing to 15.9% at 700 K and 10 Torr. At 50 Torr, the branching was measured to be 2.8% at 600 K and 6.2% at 700 K. Adduct stabilization is favored at higher pressure and lower temperature, which hinders the formation of the H-loss product. The pressure-dependent model predicted the observed branching ratios within the experimental uncertainty, indicating that the rate parameters reported here can be used in combustion mechanisms to provide insights into phenyl HACA reactions and PAH formation.}, } @article {pmid31581937, year = {2019}, author = {Jeong, CW and Kim, KH and Jang, HW and Kim, HS and Huh, JK}, title = {Dr. Chan-Woo Jeong, et al.'s reply.}, journal = {Cranio : the journal of craniomandibular practice}, volume = {37}, number = {6}, pages = {408}, doi = {10.1080/08869634.2019.1664546}, pmid = {31581937}, issn = {2151-0903}, mesh = {*Bite Force ; }, } @article {pmid31581706, year = {2019}, author = {McSherry, R and Snowden, M}, title = {Exploring Primary Healthcare Students and Their Mentors' Awareness of Mentorship and Clinical Governance as Part of a Local Continuing Professional Development (CPD) Program: Findings of a Quantitative Survey.}, journal = {Healthcare (Basel, Switzerland)}, volume = {7}, number = {4}, pages = {}, pmid = {31581706}, issn = {2227-9032}, abstract = {: Introduction: Research by Snowden [1] and Elwood et al. [2] exploring the benefits of mentoring and the place of clinical governance in enhancing care delivery illustrated an unexplored synonymous relationship between mentors and mentees (students at undergraduate and postgraduate levels) and its potential impact on patient safety and quality of care. The significance of the research was in recognizing the importance the role of the mentor can play in raising awareness of patient safety and clinical governance principles and processes in the primary healthcare setting. Aims: Building on Elwood et al.'s [2] preliminary research, this research aimed to explore primary healthcare workers and their mentor's awareness of mentorship and clinical governance as part of a local Continuing Professional Development (CPD) program. Furthermore, it aimed to establish any relationship between the mentors, the mentee, and their awareness and application of clinical governance in the primary healthcare setting. Methodology: A quantitative research design using a survey was adopted. Data Collection Instrument: The researchers integrated previously validated questionnaires incorporating Darling's [3] Measuring Mentor Potential Scale, Darwin's [4] Dimensions of Mentoring, and the Clinical Governance Awareness Questionnaire developed by McSherry and Pearce [5] into a new questionnaire. This was called "Mentorship and Clinical Governance Awareness". Sample: Convenience sample surveys were posted to complete and return to 480 primary healthcare workers undertaking post graduate study. Findings: A total of 112 completed questionnaires were included for the analysis amounting to a 23% response rate. A principle component factor analysis combining part 1-Darling's [3] characteristics of an effective mentor and part 2-Darwin's [4] personality characteristics of an effective mentor identified four primary characteristics. These are: (1) "A Facilitatory Adviser", (2) "Critically Enabling Facilitator", (3) "A Change Facilitator", and (4) "An Approachable Facilitator". These newly identified characterizations according to the primary healthcare workers significantly impacted on their awareness and application of clinical governance in primary healthcare practice. Implications for primary healthcare practice and education: The newly devised questionnaire can be used to gauge the effectiveness of mentors and mentoring and how the characteristics of the role can impact on mentee's awareness and application of clinical governance. Healthcare manager's, leaders, and educators should focus their attention on how these newly established characteristics of the mentor can influence clinical governance awareness and application in healthcare the future.}, } @article {pmid31580111, year = {2019}, author = {Reilly, D}, title = {Gender can be a continuous variable, not just a categorical one: Comment on Hyde, Bigler, Joel, Tate, and van Anders (2019).}, journal = {The American psychologist}, volume = {74}, number = {7}, pages = {840-841}, doi = {10.1037/amp0000505}, pmid = {31580111}, issn = {1935-990X}, mesh = {*Depression ; *Depressive Disorder ; Female ; Humans ; Longitudinal Studies ; Male ; Sex Factors ; }, abstract = {Hyde, Bigler, Joel, Tate, and van Anders (2019) opened debate on the treatment by psychologists and researchers of sex-gender as a dichotomous variable (male-female) and the utility of alternative conceptions. In doing so though, they framed the alternative to a gender-binary as treating gender as a categorical variable. Hyde et al.'s review obscures important contributions of a large number of psychological researchers who for decades have treated gender as a continuous variable. Their work offers a forceful contrast to the traditional gender-binary approach and also has a direct bearing on some of the questions raised by Hyde et al., including gender differences in prevalence of depression. (PsycINFO Database Record (c) 2019 APA, all rights reserved).}, } @article {pmid31573029, year = {2020}, author = {Rostila, M}, title = {Invited Commentary: Social Cohesion, Depression, and the Role of Welfare States.}, journal = {American journal of epidemiology}, volume = {189}, number = {4}, pages = {354-357}, pmid = {31573029}, issn = {1476-6256}, mesh = {Adult ; *Depression ; *Depressive Disorder ; Developed Countries ; Humans ; Interpersonal Relations ; Middle Aged ; Residence Characteristics ; }, abstract = {In this issue of the Journal, Baranyi et al. (Am J Epidemiol. 2019;000(00):000-000) examine the longitudinal associations of perceived neighborhood disorder and social cohesion with depressive symptoms among persons aged 50 years or more in 16 different countries. An important contribution of their article is that they study how neighborhood-level social capital relates to depression in different welfare-state contexts. Although the authors provide empirical evidence for some significant differences between welfare states in the relationship between social capital and depression, they say little about potential explanations. In this commentary, I draw attention to welfare-state theory and how it could provide us with a greater understanding of Baranyi et al.'s findings. I also discuss the potential downsides of grouping countries into welfare regimes. I primarily focus on the associations between social cohesion and depression, as these associations were generally stronger than those for neighborhood disorder and depression. Finally, I provide some suggestions for future research within the field and discuss whether the findings could be used to guide policies aimed at increasing social cohesion and health.}, } @article {pmid31558212, year = {2019}, author = {Menon, T}, title = {On the viability of the No Alternatives Argument.}, journal = {Studies in history and philosophy of science}, volume = {76}, number = {}, pages = {69-75}, doi = {10.1016/j.shpsa.2018.10.005}, pmid = {31558212}, issn = {0039-3681}, abstract = {If we cannot directly empirically test the claims of a particular scientific theory directly, then it would be nice to have some other criteria with which to assess its viability. In his 2013 book, String Theory and the Scientific Method, Richard Dawid aims to develop such criteria, with an eye to vindicating research programmess in disciplines where direct empirical data is scant or non-existent. In an accompanying paper, Dawid, Hartmann and Sprenger formalise Dawid's so-called 'No Alternatives Argument' (NAA) using a generalised Bayesian framework, as a first step towards formalising Dawid's entire research programme (which itself relies on two further arguments). In this paper, I argue that the formalisation of the NAA cannot play the central role in Dawid's programme as intended. This is based on the observation that not all confirmation is non-negligible confirmation. For Dawid's programme to be useful, it must demonstrate the viability not just of non-empirical theory confirmation, but of non-negligible non-empirical theory confirmation. I argue that Dawid et al.'s appeal to Bayesian confirmation theory to formalise his NAA cannot guarantee non-negligible confirmation. As a result, I conclude that if Dawid's overall project is to succeed, it must do so without the NAA formalised in this way.}, } @article {pmid31556258, year = {2020}, author = {Esquinas, AM and Karim, HMR and Mina, B}, title = {In response to Na et al.'s long-term mortality of patients discharged from the hospital after successful critical care: do we need more comprehensive data?.}, journal = {Korean journal of anesthesiology}, volume = {73}, number = {2}, pages = {171-172}, pmid = {31556258}, issn = {2005-7563}, mesh = {*Critical Care ; Hospitals, Teaching ; Humans ; Intensive Care Units ; *Patient Discharge ; Republic of Korea ; Retrospective Studies ; Tertiary Healthcare ; }, } @article {pmid31548304, year = {2019}, author = {Coruth, CL and Boyd, LD and August, JN and Smith, AN}, title = {Perceptions of Dental Hygienists About Thesis Completion in Graduate Education.}, journal = {Journal of dental education}, volume = {83}, number = {12}, pages = {1420-1426}, doi = {10.21815/JDE.019.156}, pmid = {31548304}, issn = {1930-7837}, mesh = {*Dental Hygienists ; Education, Dental, Graduate ; *Education, Graduate ; Focus Groups ; Humans ; Mentors ; Students ; }, abstract = {Few studies have been published on thesis completion experiences of master's degree students. However, for doctoral students, dissertation completion has been found to be dependent on individual, relational, and institutional factors. The aim of this study was to examine dental hygienists' perceptions of their experiences completing a thesis as a requirement for an advanced degree. A qualitative phenomenological research design was used utilizing virtual focus groups with a national purposive sample of dental hygienists (n=25) who had graduated from a degree program in which a thesis was a requirement for the degree. Data analysis used an inductive approach to identify themes using Liechty et al.'s framework of individual, relational, and institutional factors impacting completion of a dissertation. Liechty et al.'s framework is based on Vygotsky's sociocultural theory of learning. In the results, individual factors identified included family/work responsibilities, lack of understanding of the thesis process, time management, health issues, and reaching personal and professional goals. Relational factors focused primarily on positive and negative experiences with the thesis advisor/committee and support from expert peers/family. Institutional factors included the thesis structure, financial concerns, and challenges in recruiting research participants. This study found many factors influencing the thesis experience that may help guide the process in graduate degree programs. In addition, the findings suggest a need to provide mentoring and support for thesis advisors and committee members to more effectively guide students through the thesis process. Effective modifications of these may improve retention of students and facilitate timely completion of thesis research.}, } @article {pmid31541291, year = {2020}, author = {Irger, M and Willinger, L and Lacheta, L and Pogorzelski, J and Imhoff, AB and Feucht, MJ}, title = {Proximal hamstring tendon avulsion injuries occur predominately in middle-aged patients with distinct gender differences: epidemiologic analysis of 263 surgically treated cases.}, journal = {Knee surgery, sports traumatology, arthroscopy : official journal of the ESSKA}, volume = {28}, number = {4}, pages = {1221-1229}, pmid = {31541291}, issn = {1433-7347}, mesh = {Activities of Daily Living ; Athletic Injuries/*epidemiology/physiopathology ; Female ; Germany/epidemiology ; Hamstring Muscles/injuries ; Hamstring Tendons/*injuries/physiopathology ; Humans ; Incidence ; Male ; Middle Aged ; *Recovery of Function ; Rupture ; Tendon Injuries/*epidemiology/physiopathology ; }, abstract = {PURPOSE: Epidemiologic data of proximal hamstring avulsions have mainly been reported in relatively small patient cohorts. Detailed information on patient demographics, injury mechanism, and injury patterns is lacking in the literature. Since these injuries are rare and frequently misdiagnosed, a better understanding may help to increase awareness and to improve diagnosis of proximal hamstring avulsions.

METHODS: A chart review was performed to identify all patients who had undergone surgical repair for complete proximal hamstring avulsions between 01/2006 and 02/2019 at the authors' institution. The following demographic and injury-specific data were obtained: Sex, age, body mass index (BMI), cause of injury (sports, activities of daily living, and others), presence of neurologic symptoms referable to the sciatic nerve, time to surgery, injury pattern (affected tendons), tendon retraction, and type of injury according to Wood et al.`s classification (Type 1: osseous avulsions, Type 2: tear at the musculotendinous junction, Type 3: incomplete avulsion from bone, Type 4: complete avulsion with only minimal retraction, and Type 5: complete avulsion with retraction > 2 cm). Data were analyzed for the entire study population and group comparison was performed with regard to sex, cause of injury, and the type of injury.

RESULTS: A total of 263 patients were included (53% male). The mean age was 49 ± 13 years with most patients (56%) aged between 45-59 years. Most injuries occurred while participating in sports (52%) and injury type 5 was most commonly diagnosed (66%). Five percent of patients had sensory deficits referable to the sciatic nerve. Gender comparison showed that female patients were significantly older, predominantly represented in the age group 45-59 years, and most commonly injured during activities of daily living, whereas male patients were significantly more often represented in younger age groups, and the most common cause of injury was sports. Compared to Type 4 and 5 injuries, patients with a Type 1 injury were significantly younger and had a significantly longer time to surgery.

CONCLUSION: Proximal hamstring avulsion occurs predominately in the middle-aged patient and only rarely in patients under the age of 30 years. No gender dominance exists. Female patients are typically older and get injured during activities of daily living, whereas male patients are younger and get injured more often during sports. These epidemiologic data may help physicians to make an accurate and early diagnosis.

LEVEL OF EVIDENCE: IV.}, } @article {pmid31537206, year = {2019}, author = {White, PJ and Lewis, J}, title = {[Response to Kounali et al.'s letter of response].}, journal = {Epidemiology and infection}, volume = {147}, number = {}, pages = {e273}, pmid = {31537206}, issn = {1469-4409}, support = {MR/R015600/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {*Chlamydia trachomatis ; England ; Female ; Humans ; Prevalence ; Probability ; Scotland ; Surveys and Questionnaires ; Wales ; }, } @article {pmid31516242, year = {2019}, author = {Shah, S and Singaraju, S and Bertin, ET and Singaraju, M and Sharma, A}, title = {Quantification of micronuclei in exfoliated cells of human immunodeficiency virus/AIDS-infected female patients.}, journal = {Journal of oral and maxillofacial pathology : JOMFP}, volume = {23}, number = {2}, pages = {301}, pmid = {31516242}, issn = {0973-029X}, abstract = {BACKGROUND: Micronucleus (MN) is a biomarker for cytotoxicity, which is formed during cell division. Increased MN scoring has been successfully used to recognize population groups at risk for cancers of oral cavity, cervix, urinary bladder and esophagus. Incorporating MN score along with cytological smear testing gives a better and cost-effective screening for high-risk patients.

OBJECTIVE: This study evaluated the effectiveness of using MN score assessed from Papanicolaou (PAP) smears, as a biomarker for chromosomal damage in human immunodeficiency virus (HIV) patients.

MATERIALS AND METHODS: Oral smears of 25 female HIV/AIDS patients, without habits such as chewing or smoking tobacco, and taking antiretroviral therapy (ART) at ART center, were recruited for the study. After careful oral examination and oral rinsing with normal saline, smears were prepared on slides by scraping the buccal mucosa with a wooden spatula. All the slides were fixed in 95% ethyl alcohol and stained with PAP stain, and 1000 cells were counted per patient. Based on Tolbert et al.'s criteria, MNs were identified, and quantitative scoring of MN was done on the basis of morphological assay.

RESULTS: Mean ± standard deviation values of frequency of MNs in HIV-infected females were 73.40 ± 19.70 and in normal females were 38.08 ± 8.56.

CONCLUSION: MN scoring on the epithelial cells of buccal mucosa can be used as a biomarker in screening procedures for HIV patients.}, } @article {pmid31509286, year = {2019}, author = {Stubbing, EA and Helmich, E and Cleland, J}, title = {Medical student views of and responses to expectations of professionalism.}, journal = {Medical education}, volume = {53}, number = {10}, pages = {1025-1036}, doi = {10.1111/medu.13933}, pmid = {31509286}, issn = {1365-2923}, mesh = {Adult ; Clinical Competence ; Female ; Focus Groups ; Humans ; Male ; Professionalism/*standards ; Qualitative Research ; Schools, Medical ; Students, Medical/*psychology/statistics & numerical data ; }, abstract = {CONTEXT: To earn society's trust, medical students must develop professional values and behaviours via a transformative process, from lay person to doctor. Yet students are expected to epitomise the values and behaviours of a doctor from the outset of medical school, leading them to feel 'judged all the time' (in terms of their professionalism). Our aim, therefore, is to extend knowledge exploring the expectations communicated to and perceived by medical students and to provide a conceptually framed understanding of students' associated emotional tensions.

METHODS: We used a qualitative exploratory case study methodology within a constructivist paradigm to explore the messages communicated about professionalism and students' perceived expectations of professionalism in one medical school. Data were collected in the form of: (i) regulatory and medical school documents, and (ii) focus groups with 23 participants in their first 2 years at medical school. We used thematic analysis for data interpretation and two theoretical lenses, Amalberti et al.'s framework of system migration for health care and Sinclair's adaptation of Goffman's dramaturgical theory, to critically analyse the results.

RESULTS: We found messages and perceived expectations of knowledge and competence, and the need to ensure trust. We also identified that the expectations of patients, doctors, society, family and friends are just as, if not more, influential than policy and regulatory expectations for early years' medical students. Moreover, we found tensions, with students feeling that the expectations of them from others were unrealistic for their level of training. With this came a sense of pressure to meet expectations that participants responded to by acting as if already competent.

CONCLUSIONS: Our findings suggest that external forces (expectations) drive early years' students to act as if competent. Although this is part of student identity formation it could also have implications for patient safety and therefore necessitates recognition and support from educators.}, } @article {pmid31500896, year = {2019}, author = {Rutherford, BR}, title = {Editorial on Maharani et al.'s "Hearing Impairment, Loneliness, Social Isolation and Cognitive Function: Longitudinal Analysis Using English Longitudinal Study on Ageing".}, journal = {The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry}, volume = {27}, number = {12}, pages = {1357-1359}, doi = {10.1016/j.jagp.2019.08.009}, pmid = {31500896}, issn = {1545-7214}, mesh = {Aging ; Cognition ; *Hearing Loss ; Humans ; *Loneliness ; Longitudinal Studies ; Social Isolation ; }, } @article {pmid31499715, year = {2019}, author = {Li, R and Li, XY and Xiong, Y and Jiang, A and Lee, D}, title = {An IPVO-based reversible data hiding scheme using floating predictors.}, journal = {Mathematical biosciences and engineering : MBE}, volume = {16}, number = {5}, pages = {5324-5345}, doi = {10.3934/mbe.2019266}, pmid = {31499715}, issn = {1551-0018}, abstract = {This work optimizes an improved high-fidelity reversible data hiding scheme of Peng et al. which is based on improved pixel-value-ordering (IPVO) and prediction-error expansion. In Peng et al.'s method, the difference between the maximum and second largest value (or, the minimum and second smallest value) of a block is defined considering the pixel locations of maximum and second the largest value (or, the pixel locations of minimum and second the smallest value). When the difference between the maximum and second largest value (or, the minimum and second smallest value) of a block is equal to 0 or 1, the block can be exploited to embed data. Otherwise, the block should be shifted or remain unchanged. However, different prediction-error used to embed information can lead to different histogram modification and different pixel shift rate, to further reduces the change in the carrier image. In this work, we list all the different prediction-error, which are used as the selection object for the embedded error when hiding information. As a prerequisite of meeting the demand of the embedding capacity, some appropriate prediction-errors are selected for embedding to reduce the number of the pixel shifted in the marked image as small as possible. An IPVO-based reversible data hiding scheme with floating predictor is also extended. Experimental results show that the proposed scheme yields a superior performance than the state-of-the-art works, under the condition of same embedding capacity, especially for relatively rough images.}, } @article {pmid31499619, year = {2019}, author = {Liu, YX and Yang, CN and Sun, QD}, title = {Enhance embedding capacity for switch map based multi-group EMD data hiding.}, journal = {Mathematical biosciences and engineering : MBE}, volume = {16}, number = {5}, pages = {3382-3392}, doi = {10.3934/mbe.2019169}, pmid = {31499619}, issn = {1551-0018}, abstract = {Exploiting Modification Direction (EMD) based data hiding achieves good stego-image quality and high security level. Recently, a section-wise EMD was proposed to enhance the embedding capacity of EMD. Later, Wang et al. introduced a switch map based multi-group EMD to further improve the embedding capacity. However, by a detail observation on the switch map in Wang et al.'s scheme, we find that more codewords with longer code-length can be put into the switch map. In this paper, we build a new switch map by Huffman code, and construct an enhanced multi-group EMD using Huffman code based switch map. Our scheme has higher embedding capacity than Wang et al.'s scheme and other EMD based data hiding methods.}, } @article {pmid31493613, year = {2019}, author = {Guo, S and Wang, L and Xie, Y and Luo, X and Zhang, S and Xiong, L and Ai, H and Yuan, Z and Wang, J}, title = {Bibliometric and Visualized Analysis of Stem Cells Therapy for Spinal Cord Injury Based on Web of Science and CiteSpace in the Last 20 Years.}, journal = {World neurosurgery}, volume = {132}, number = {}, pages = {e246-e258}, doi = {10.1016/j.wneu.2019.08.191}, pmid = {31493613}, issn = {1878-8769}, mesh = {*Bibliometrics ; Humans ; Journal Impact Factor ; Spinal Cord Injuries/*therapy ; Stem Cell Transplantation/*methods ; }, abstract = {OBJECTIVE: To provide an analysis of Web of Science (WoS) indexed literature related to stem cells therapy in spinal cord injury published between 1999 and 2018.

METHODS: Data were obtained from the WoS Core Collection on March 30, 2019. Qualitative and quantitative analysis was conducted based on WoS. Co-citation analysis, collaboration analysis, and co-words analysis of keywords was conducted by using CiteSpace.

RESULTS: A total of 4188 references were obtained. The number of publications continually increased over the investigated period. Articles were the most frequently document type. Cell Transplantation (127) was the most productive journal. Experimental Neurology (2180) was the most frequently co-cited journal. H. Okano was the most productive and influential author, with 98 publications and 4860 cited counts. The most productive country and institution were the United States and University of Toronto, respectively. Researchers and institutions from Canada, the United States, Japan, and China were the core research forces. There was a broad and close cooperation worldwide. The Lu et al.'s (2012) article (co-citation counts, 177) was the most representative and symbolic reference. Transplantation, functional recovery, marrow-derived mesenchymal stem cell treatment, and progenitor cells were the hot spots. Inflammation, glial scar, nerve regeneration, neurite outgrowth, and bone marrow stromal cell were research frontiers.

CONCLUSIONS: Research on stem cells for spinal cord injury is a well-developed and promising research field. There is broad global scientific research cooperation. More cooperation among top authors, institutions, and countries is needed. Our results may be helpful for researchers in identifying further potential perspectives on collaborators, research frontiers, and hot topics.}, } @article {pmid31489130, year = {2019}, author = {Brand, BL and Loewenstein, RJ and Schielke, HJ and van der Hart, O and Nijenhuis, ERS and Schlumpf, YR and Vissia, EM and Jepsen, EKK and Reinders, AATS}, title = {Cautions and concerns about Huntjens et al.'s Schema Therapy for Dissociative Identity Disorder.}, journal = {European journal of psychotraumatology}, volume = {10}, number = {1}, pages = {1631698}, pmid = {31489130}, issn = {2000-8066}, } @article {pmid31485684, year = {2019}, author = {Bouras, T and Kuiper, JH and Barnett, A}, title = {Isolated medial patellofemoral ligament reconstruction significantly improved quality of life in patients with recurrent patella dislocation: a response to Hiemstra et al.'s letter to the editor.}, journal = {Knee surgery, sports traumatology, arthroscopy : official journal of the ESSKA}, volume = {27}, number = {11}, pages = {3735-3737}, pmid = {31485684}, issn = {1433-7347}, mesh = {Humans ; Knee Joint ; Ligaments, Articular ; *Patella ; *Patellar Dislocation ; Quality of Life ; }, } @article {pmid31482489, year = {2020}, author = {Hooley, C and Amano, T and Markovitz, L and Yaeger, L and Proctor, E}, title = {Assessing Implementation Strategy Reporting in the Mental Health Literature: A Narrative Review.}, journal = {Administration and policy in mental health}, volume = {47}, number = {1}, pages = {19-35}, pmid = {31482489}, issn = {1573-3289}, support = {P50 CA244431/CA/NCI NIH HHS/United States ; R25 MH080916/MH/NIMH NIH HHS/United States ; T32 MH019960/MH/NIMH NIH HHS/United States ; 1620-87686/TR/NCATS NIH HHS/United States ; }, mesh = {Evidence-Based Practice/*organization & administration ; Health Plan Implementation/*organization & administration ; Humans ; Implementation Science ; *Mental Health ; Research/*organization & administration ; }, abstract = {Inadequate implementation strategy reporting restricts research synthesis and replicability. We explored the implementation strategy reporting quality of a sample of mental health articles using Proctor et al.'s (Implement Sci 8:139, 2013) reporting recommendations. We conducted a narrative review to generate the sample of articles and assigned a reporting quality score to each article. The mean article reporting score was 54% (range 17-100%). The most reported domains were: name (100%), action (82%), target (80%), and actor (67%). The least reported domains included definition (6%), temporality (26%), justification (34%), and outcome (37%). We discuss limitations and provide recommendations to improve reporting.}, } @article {pmid31476696, year = {2019}, author = {Bateman, JE and Birney, DP}, title = {The link between working memory and fluid intelligence is dependent on flexible bindings, not systematic access or passive retention.}, journal = {Acta psychologica}, volume = {199}, number = {}, pages = {102893}, doi = {10.1016/j.actpsy.2019.102893}, pmid = {31476696}, issn = {1873-6297}, mesh = {Female ; Humans ; Intelligence/*physiology ; Male ; Memory, Short-Term/*physiology ; Mental Recall/physiology ; Photic Stimulation/methods ; Random Allocation ; Retention, Psychology/*physiology ; Young Adult ; }, abstract = {Rather than working memory capacity acting as a distinct subordinate function of fluid intelligence, there is an emerging consensus that their relationship can be understood as an outcome of common functions dictated by the strength and flexibility of bindings which integrate representations relationally. The current study considers the Arithmetic Chain Task (Oberauer, Demmrich, Mayr, & Kliegl, 2001) which contrasts access (integrating previously stored information for use in the arithmetic processing) against mere retention (holding previously stored information for recall after the arithmetic processing). Participants (n = 122) completed the Arithmetic Chain Task (ACT) with a novel manipulation that split the access condition into fixed-order vs. random-order access. Both forms of access require integration of previously stored information into the arithmetic, but random-order access restricts systematic chunking, necessitating multiple flexible bindings that can be updated in light of new information. Participants also completed a measure of working memory and a measure of fluid intelligence. Results replicated Oberauer et al.'s findings on a demarcation between retention and access, though the current data indicate that random-order presentation is necessary to distinguish access from retention. Crucially, this random-order access is also required to link the ACT to a factor representing the commonality in WM and Gf. These results suggest that what is common to WM and Gf is the capacity to maintain multiple durable and flexible bindings.}, } @article {pmid31456446, year = {2021}, author = {Slezak, P}, title = {Reply to Del Gaizo et al.'s "The SPOT GRADE: A Clinically Validated, Quantitative Bleeding Severity Scale".}, journal = {Journal of investigative surgery : the official journal of the Academy of Surgical Research}, volume = {34}, number = {5}, pages = {558-560}, doi = {10.1080/08941939.2019.1651431}, pmid = {31456446}, issn = {1521-0553}, mesh = {*Dehydration ; Humans ; }, } @article {pmid31449857, year = {2019}, author = {Weijer, C and Taljaard, M}, title = {The ethics of cluster randomized trials: response to a proposal for revision of the Ottawa Statement.}, journal = {Journal of clinical epidemiology}, volume = {116}, number = {}, pages = {140-145}, doi = {10.1016/j.jclinepi.2019.08.006}, pmid = {31449857}, issn = {1878-5921}, support = {PJT-153045//CIHR/Canada ; }, mesh = {*Ethics Committees, Research ; Humans ; *Informed Consent ; Randomized Controlled Trials as Topic ; Research Personnel ; }, abstract = {BACKGROUND AND OBJECTIVES: Cluster randomized trials are commonly used to evaluate public health, knowledge translation, and health service interventions. Cluster trials raise novel ethical issues, however, and the Ottawa Statement on the Ethical Design and Conduct of Cluster Randomized Trials (2012) provides researchers and research ethics committees with needed guidance. In this journal, van der Graaf et al. reflect on the Ottawa Statement and propose three revisions. In this paper, we respond to each of these proposed revisions.

RESULTS: First, van der Graaf et al. argue that patients who are merely indirectly affected by study interventions ought nonetheless to be considered research participants. We disagree. So long as the practice change is evidence based and the physician continues to make individualized judgments regarding patient care, patient liberty and welfare interests are not substantially affected. Second, although they agree that health providers who are targeted are research participants, they argue that such providers ought to be treated differently and should not be allowed to withdraw from a study too easily. In our view, this position fails to weigh adequately the potential for coercion and harms faced by employees in research. Third, they argue that the potential for bias may require blinding participants to allocation and study interventions in the consent process of a cluster trial. We agree on this point and support this approach in a limited set of cases.

CONCLUSION: While we reject two of van der Graaf et al.'s proposed revisions, we agree that further guidance on informed consent and study bias is needed.}, } @article {pmid31447750, year = {2019}, author = {Hsieh, CW and Sharma, D}, title = {Priming Emotional Salience Reveals the Role of Episodic Memory and Task Conflict in the Non-color Word Stroop Task.}, journal = {Frontiers in psychology}, volume = {10}, number = {}, pages = {1826}, pmid = {31447750}, issn = {1664-1078}, abstract = {Previous research attempted to account for the emotional Stroop effect based on connectionist models of the Stroop task that implicate conflict in the output layer as the underlying mechanism (e.g., Williams et al., 1996). Based on Kalanthroff et al.'s (2015) proactive-control/task-conflict (PC-TC) model, our study argues that the interference from non-color words (neutral and negative words) is due to task conflict. Using a study-test procedure 120 participants (59 high and 61 low trait anxiety) studied negative and neutral control words prior to being tested on a color responding task that included studied and unstudied words. The results for the low anxiety group show no emotional Stroop effect, but do demonstrate the slowdown in response latencies to a block of studied and unstudied words compared to a block of unstudied words. In contrast, the high anxiety group shows (a) an emotional Stroop effect but only for studied negative words and (b) a reversed sequential modulation in which studied negative words slowed down the color-responding of studied negative words on the next trial. We consider how these findings can be incorporated into the PC-TC model and suggest the interacting role of trait anxiety, episodic memory, and emotional salience driving attention that is based on task conflict.}, } @article {pmid31447306, year = {2019}, author = {Lord, JS}, title = {Comments on T. De Meeûs et al.'s Article.}, journal = {Trends in parasitology}, volume = {35}, number = {10}, pages = {741-742}, doi = {10.1016/j.pt.2019.07.011}, pmid = {31447306}, issn = {1471-5007}, mesh = {Animals ; *Trypanosomiasis ; *Trypanosomiasis, African ; *Tsetse Flies ; }, } @article {pmid31446373, year = {2020}, author = {Uchida, Y and Takemura, K and Fukushima, S}, title = {How do socio-ecological factors shape culture? Understanding the process of micro-macro interactions.}, journal = {Current opinion in psychology}, volume = {32}, number = {}, pages = {115-119}, doi = {10.1016/j.copsyc.2019.06.033}, pmid = {31446373}, issn = {2352-2518}, mesh = {*Culture ; Humans ; *Social Behavior ; *Social Environment ; *Social Interaction ; }, abstract = {Socio-ecological environments produce certain psychological functions. that are adaptive for survival in each environment. Past evidence suggests that interdependence-related psychological features are prevalent in East Asian cultures partly due to the history of 'rice-crop farming' (versus herding) in those areas. However, it is unclear how and why certain functional behaviors required by the socio-ecological environment are sublimated to become cultural values, which are then transmitted and shared among people. In this paper, we conceptually review the works examining various macro sharing processes for cultural values, and focus on the use of multilevel analysis in elucidating the effect of both macro and individual level factors. Uchida et al.'s study (2019) suggests that collective activities at the macro level (community-level), which is required by a certain socio-ecological environment, promote interdependence not only among farmers but also non-farmers. The multilevel processes of how psychological characteristics are construed by macro factors will be discussed.}, } @article {pmid31430911, year = {2019}, author = {Yu, S and Park, K and Park, Y}, title = {A Secure Lightweight Three-Factor Authentication Scheme for IoT in Cloud Computing Environment.}, journal = {Sensors (Basel, Switzerland)}, volume = {19}, number = {16}, pages = {}, pmid = {31430911}, issn = {1424-8220}, abstract = {With the development of cloud computing and communication technology, users can access the internet of things (IoT) services provided in various environments, including smart home, smart factory, and smart healthcare. However, a user is insecure various types of attacks, because sensitive information is often transmitted via an open channel. Therefore, secure authentication schemes are essential to provide IoT services for legal users. In 2019, Pelaez et al. presented a lightweight IoT-based authentication scheme in cloud computing environment. However, we prove that Pelaez et al.'s scheme cannot prevent various types of attacks such as impersonation, session key disclosure, and replay attacks and cannot provide mutual authentication and anonymity. In this paper, we present a secure and lightweight three-factor authentication scheme for IoT in cloud computing environment to resolve these security problems. The proposed scheme can withstand various attacks and provide secure mutual authentication and anonymity by utilizing secret parameters and biometric. We also show that our scheme achieves secure mutual authentication using Burrows-Abadi-Needham logic analysis. Furthermore, we demonstrate that our scheme resists replay and man-in-the-middle attacks usingthe automated validation of internet security protocols and applications (AVISPA) simulation tool. Finally, we compare the performance and the security features of the proposed scheme with some existing schemes. Consequently, we provide better safety and efficiency than related schemes and the proposed scheme is suitable for practical IoT-based cloud computing environment.}, } @article {pmid31425931, year = {2019}, author = {Fontaine, G and Cossette, S and Maheu-Cadotte, MA and Mailhot, T and Heppell, S and Roussy, C and Côté, J and Gagnon, MP and Dubé, V}, title = {Behavior change counseling training programs for nurses and nursing students: A systematic descriptive review.}, journal = {Nurse education today}, volume = {82}, number = {}, pages = {37-50}, doi = {10.1016/j.nedt.2019.08.007}, pmid = {31425931}, issn = {1532-2793}, mesh = {Behavior Therapy/*education/methods ; Counseling/*methods/trends ; Humans ; Nurses/*psychology/statistics & numerical data ; Qualitative Research ; Students, Nursing/*psychology/statistics & numerical data ; Surveys and Questionnaires ; Teaching/psychology/standards ; }, abstract = {OBJECTIVES: (1) To systematically review the literature on behavior change counseling (BCC) training programs targeting nurses and nursing students; (2) to characterize these training programs according to their content (i.e., targeted health behavior[s], BCC approaches taught, BCC techniques taught), structure, and modes of delivery.

DESIGN: A systematic, descriptive literature review.

DATA SOURCES: PubMed, CINAHL and Embase were searched with no time limitation in August 2018.

REVIEW METHODS: A systematic, descriptive literature review structured according to Paré et al.'s methodology and the PRISMA guidelines. Primary studies were included if they evaluated a BCC training program with nurses or nursing students. Review authors screened studies, extracted data, and assessed study quality using the MERSQI. Data was synthesized through narrative synthesis, descriptive statistics, and content analysis.

RESULTS: From a pool of 267 articles, we included 25 articles published between 2003 and 2018. Two studies scored as low quality (8%), 18 as moderate quality (72%), and 5 as high quality (20%). Physical activity (n = 14; 56%) and smoking (n = 11; 44%) were the most frequently targeted health behaviors. Eleven BCC approaches were cited (e.g., motivational interviewing), and 48 BCC techniques were identified (e.g., eliciting and scaling change talk). The median number of training sessions was 3 (interquartile range [IQR] 5), the median training program duration was 3 h (IQR 6.25 h), and median training period was 24.5 days (IQR 110 days). Programs were most often delivered as seminars and workshops.

CONCLUSIONS: High-quality studies reporting the assessment of BCC training programs with nurses and nursing students are scarce. There was significant heterogeneity in terms of the BCC approaches and techniques taught. Current evidence suggests nurses and nursing students learn BCC mainly through active, realistic practice. However, computer-based training programs are rapidly gaining ground. Further research emphasizing theory-based BCC training programs is warranted.}, } @article {pmid31419992, year = {2019}, author = {Cancelliere, C and Sutton, D and Côté, P and French, SD and Taylor-Vaisey, A and Mior, SA}, title = {Implementation interventions for musculoskeletal programs of care in the active military and barriers, facilitators, and outcomes of implementation: a scoping review.}, journal = {Implementation science : IS}, volume = {14}, number = {1}, pages = {82}, pmid = {31419992}, issn = {1748-5908}, mesh = {Delivery of Health Care/economics/*organization & administration/standards ; Efficiency, Organizational ; Environment ; Evidence-Based Practice/organization & administration ; Humans ; *Military Personnel ; Musculoskeletal Diseases/*therapy ; Outcome and Process Assessment, Health Care ; Patient Satisfaction ; Patient-Centered Care/organization & administration ; Social Environment ; Time Factors ; }, abstract = {BACKGROUND: Musculoskeletal disorders are common in the active military and are associated with significant lost duty days and disability. Implementing programs of care to manage musculoskeletal disorders can be challenging in complex healthcare systems such as in the military. Understanding how programs of care for musculoskeletal disorders have been implemented in the military and how they impact outcomes may help to inform future implementation interventions in this population.

METHODS: We conducted a scoping review using the modified Arksey and O'Malley framework to identify literature on (1) implementation interventions of musculoskeletal programs of care in the active military, (2) barriers and facilitators of implementation, and (3) implementation outcomes. We identified studies published in English by searching MEDLINE, CINAHL, Embase, and CENTRAL (Cochrane) from inception to 1 June 2018 and hand searched reference lists of relevant studies. We included empirical studies. We synthesized study results according to three taxonomies: the Effective Practice and Organization of Care (EPOC) taxonomy to classify the implementation interventions; the capability, opportunity, motivation-behavior (COM-B) system to classify barriers and facilitators of implementation; and Proctor et al.'s taxonomy (Adm Policy Ment Health 38:65-76, 2011) to classify outcomes in implementation research.

RESULTS: We identified 1785 studies and 16 were relevant. All but two of the relevant studies were conducted in the USA. Implementation interventions were primarily associated with delivery arrangements (e.g., multidisciplinary care). Most barriers or facilitators of implementation were environmental (physical or social). Service and client outcomes indicated improved efficiency of clinical care and improved function and symptomology. Studies reporting implementation outcomes indicated the programs were acceptable, appropriate, feasible, or sustainable.

CONCLUSION: Identification of evidence-based approaches for the management of musculoskeletal disorders is a priority for active-duty military. Our findings can be used by military health services to inform implementation strategies for musculoskeletal programs of care. Further research is needed to better understand (1) the components of implementation interventions, (2) how to overcome barriers to implementation, and (3) how to measure implementation outcomes to improve quality of care and recovery from musculoskeletal disorders.}, } @article {pmid31417209, year = {2019}, author = {Satoh, Y and Yamada, T and Shimamura, R and Ohmi, T}, title = {Comparison of foot kinetics and kinematics during gait initiation between young and elderly participants.}, journal = {Journal of physical therapy science}, volume = {31}, number = {7}, pages = {498-503}, pmid = {31417209}, issn = {0915-5287}, abstract = {[Purpose] To investigate the differences in foot kinetics during gait initiation between young and elderly participants using a modified multi-segment foot model. [Participants and Methods] Twelve young (23.3 ± 2.4 years) and 12 elderly participants (73.3 ± 3.9 years) were included in this study. Gait initiation was measured using a three-dimensional motion analysis system. We calculated the kinetic and kinematic values using our modified multi-segment foot model and compared those values with the values calculated using Bruening et al.'s multi-segment foot model. Modified gait initiation values were also compared between the elderly and young participants. [Results] Our modified multi-segment foot model, created using the Software for Interactive Musculoskeletal Modeling, showed similar values to those reported by Bruening et al. When we compared gait initiation between the elderly participants and their younger counterparts, the elderly exhibited lower torque and power values in the ankle, tarsometatarsal, and metatarsophalangeal joints. Additionally, the elderly exhibited a lower torque ratio in the distal joint than in the proximal joint (torque ratio: ankle joint >tarsometatarsal joint >metatarsophalangeal joint). [Conclusion] The elderly participants had less speed, stride, foot joint movement, moment, and power than the young participants. Moreover, the ratio of joint moment was smaller in the elderly participants. In elderly patients whose walking speed has decreased, consideration of the kinetics of the foot is important when deciding physiotherapy intervention.}, } @article {pmid31402558, year = {2019}, author = {Sun, W and Xiao, X and Zhang, Q}, title = {Correspondence to Rossetti et al.'s review of the phenotypic spectrum associated with haploinsufficiency of MYRF.}, journal = {American journal of medical genetics. Part A}, volume = {179}, number = {11}, pages = {2315-2316}, doi = {10.1002/ajmg.a.61326}, pmid = {31402558}, issn = {1552-4833}, support = {30971588//National Natural Science Foundation of China/International ; 81600768//National Natural Science Foundation of China/International ; 81770965//National Natural Science Foundation of China/International ; //Fundamental Research Funds of the State Key Laboratory of Ophthalmology/International ; }, mesh = {*Haploinsufficiency ; Membrane Proteins/genetics ; Transcription Factors/*genetics ; }, } @article {pmid31402474, year = {2019}, author = {van der Schaaf, M}, title = {Learning through the senses.}, journal = {Medical education}, volume = {53}, number = {10}, pages = {960-962}, pmid = {31402474}, issn = {1365-2923}, mesh = {*Health Occupations ; *Learning ; }, abstract = {van der Schaaf comments on Kelly et al.'s study to further explain how the concept of embodied cognition can impact health professionals' learning and learning environments.}, } @article {pmid31385520, year = {2020}, author = {Van Aken, B}, title = {Response to the note to editor: Comments on "transcriptomic response of Arabidopsis thaliana exposed to hydroxylated polychlorinated biphenyls (OH-PCBs)".}, journal = {International journal of phytoremediation}, volume = {22}, number = {2}, pages = {224-225}, doi = {10.1080/15226514.2019.1645090}, pmid = {31385520}, issn = {1549-7879}, mesh = {*Arabidopsis ; Biodegradation, Environmental ; *Environmental Pollutants ; Hydroxylation ; *Polychlorinated Biphenyls ; Transcriptome ; }, abstract = {In response to Dr. Yang et al.'s comments on our article "Transcriptomic response of Arabidopsis thaliana exposed to hydroxylated polychlorinated biphenyls (OH-PCBs)", additional details were provided regarding the analysis of the gene expression level (One-Way Between-Subject ANOVA) and correction for false discovery rate (FDR) (Benjamini-Hochberg). The gene expression analysis was performed again using the new release of the Transcriptome Analysis Console™ (version 4.0.1, Life Technologies - not available at the time our initial study was conducted), which integrates the Limma differential expression portion of the Bioconductor package. Overall similar results were obtained regarding the number of genes differentially expressed and the enrichment of genes in different Gene Ontology (GO) categories. The transcriptomic profiles induced in response to the three OH-derivatives were shown, again, to be similar to those induced by inhibitors of the brassinosteroid synthesis (i.e., brassinazole, propiconazole, and uniconazole), potentially resulting in iron deficiency in exposed plants. The new (and improved) method used for the selection of differentially expressed genes did not change the conclusion of our initial study, which suggested that the higher phytotoxicity of OH-derivatives, as compared to the parent compound 2,5-dichlorobiphenyl (2,5-DCB), may be explained by the inhibition of the brassinosteroid synthesis pathway.}, } @article {pmid31368638, year = {2020}, author = {Redshaw, J and Nielsen, M and Slaughter, V and Kennedy-Costantini, S and Oostenbroek, J and Crimston, J and Suddendorf, T}, title = {Individual differences in neonatal "imitation" fail to predict early social cognitive behaviour.}, journal = {Developmental science}, volume = {23}, number = {2}, pages = {e12892}, doi = {10.1111/desc.12892}, pmid = {31368638}, issn = {1467-7687}, mesh = {Attention ; Cognition/*physiology ; Female ; Humans ; Imitative Behavior/*physiology ; *Individuality ; Infant ; Infant, Newborn ; Intention ; Longitudinal Studies ; Male ; *Social Behavior ; }, abstract = {The influential hypothesis that humans imitate from birth - and that this capacity is foundational to social cognition - is currently being challenged from several angles. Most prominently, the largest and most comprehensive longitudinal study of neonatal imitation to date failed to find evidence that neonates copied any of nine actions at any of four time points (Oostenbroek et al., [2016] Current Biology, 26, 1334-1338). The authors of an alternative and statistically liberal post-hoc analysis of these same data (Meltzoff et al., [2017] Developmental Science, 21, e12609), however, concluded that the infants actually did imitate one of the nine actions: tongue protrusion. In line with the original intentions of this longitudinal study, we here report on whether individual differences in neonatal "imitation" predict later-developing social cognitive behaviours. We measured a variety of social cognitive behaviours in a subset of the original sample of infants (N = 71) during the first 18 months: object-directed imitation, joint attention, synchronous imitation and mirror self-recognition. Results show that, even using the liberal operationalization, individual scores for neonatal "imitation" of tongue protrusion failed to predict any of the later-developing social cognitive behaviours. The average Spearman correlation was close to zero, mean rs = 0.027, 95% CI [-0.020, 0.075], with all Bonferroni adjusted p values > .999. These results run counter to Meltzoff et al.'s rebuttal, and to the existence of a "like me" mechanism in neonates that is foundational to human social cognition.}, } @article {pmid31361182, year = {2019}, author = {Maleknejad, A and Dastyar, N and Badakhsh, M and Balouchi, A and Rafiemanesh, H and Al Rawajfah, O and Rezaie Keikhaie, K and Sheyback, M}, title = {Surgical site infections in Eastern Mediterranean region: a systematic review and meta-analysis.}, journal = {Infectious diseases (London, England)}, volume = {51}, number = {10}, pages = {719-729}, doi = {10.1080/23744235.2019.1642513}, pmid = {31361182}, issn = {2374-4243}, mesh = {Adult ; Cross Infection/epidemiology ; Cross-Sectional Studies ; Female ; Humans ; Longitudinal Studies ; Male ; Mediterranean Region ; Middle Aged ; Prospective Studies ; Retrospective Studies ; Surgical Wound Infection/*epidemiology ; Young Adult ; }, abstract = {Background: Surgical site infections (SSIs) are the most common and costly type of hospital-acquired infections (HAIs) worldwide. Despite individual studies, there is also no clear statistics on the SSI prevalence rate in the East Mediterranean region. The aim of this study was to investigate the prevalence of SSI in the Eastern Mediterranean region. Methods: This systematic review and meta-analysis were performed by searching three international databases (Web of Science, PubMed and Scopus) from 1 January 2001 to 31 December 2018. The keywords used included 'Prevalence' OR 'incidence' OR 'surgical site infection' OR 'wound infection' OR 'Postoperative Wound Infections' and 'Middle east'. The Hoy et al.'s tool was used to evaluate the quality of the articles. Result: Out of 889 initial studies, 40 studies from 12 countries of the Eastern Mediterranean region were included in the final stage of the study. Based on the results of random effect method, the overall prevalence of SSI in 137,452 patients was 7.9% (95% Confidence Interval (CI): 7.1, 8.8; I[2]=96.7%). The prevalence of SSI in cardiac surgery and general surgery wards was 10 and 9.2%, respectively. The prevalence of SSI was lower in women than in males, although this difference was related to caesarean section. Conclusions: Considering the high prevalence of SSI in the Eastern Mediterranean region, timely diagnosis, proper prevention and postoperative control are necessary in the region using the same international guides in all countries.}, } @article {pmid35530594, year = {2019}, author = {Luo, WZ and Chen, GH and Xiao, ST and Wang, Q and Huang, ZK and Wang, LY}, title = {The enzyme-like catalytic hydrogen abstraction reaction mechanisms of cyclic hydrocarbons with magnesium-diluted Fe-MOF-74.}, journal = {RSC advances}, volume = {9}, number = {41}, pages = {23622-23632}, pmid = {35530594}, issn = {2046-2069}, abstract = {Enzymatic heme and non-heme Fe(iv)-O species usually play an important role in hydrogen abstraction of biocatalytic reactions, yet duplicating the reactivity in biomimicry remains a great challenge. Based on Xiao et al.'s experimental work [Nat. Chem., 2014, 6(7), 590], we theoretically found that in the presence of the oxidant N2O, the enzyme-like metal organic framework, i.e., magnesium-diluted Fe-MOF-74 [Fe/(Mg)-MOF-74] can activate the C-H bonds of 1,4-cyclohexadiene (CHD) into benzene with a two-step hydrogen abstraction mechanism based on the density functional theory (DFT) level. It is shown that the first transition state about the cleavage of the N-O bond of N2O to form the Fe(iv)-O species is the rate-determining step with activation enthalpy of 19.4 kcal mol[-1] and the complete reaction is exothermic by 62.8 kcal mol[-1] on quintet rather than on triplet PES. In addition, we proposed a rebound mechanism of cyclic cyclohexane (CHA) hydroxylation to cyclohexanol which has not been studied experimentally. Note that the activation enthalpies on the first hydrogen abstraction for both cyclic CHD and cyclohexane are just 8.1 and 3.5 kcal mol[-1], respectively, which are less than that of 13.9 kcal mol[-1] for chained ethane. Most importantly, for the hydrogen abstraction of methane catalyzed by M/(Mg)-MOF-74 (M = Cu, Ni, Fe, and Co), we found that the activation enthalpies versus the C-H bond length of methane of TSs, NPA charge of the reacting oxyl atom have linear relationships with different slopes, i.e., shorter C-H bond and less absolute value of NPA charge of oxyl atom are associated with lower activation enthalpy; while for the activation of methane, ethane, propane and CHD catalyzed by Fe/(Mg)-MOF-74, there also exists positive correlations between activation enthalpies, bond dissociation energies (BDEs) and C-H bond lengths in TSs, respectively. We hope the present theoretical study may provide the guideline to predict the performance of MOFs in C-H bond activation reactions.}, } @article {pmid31356700, year = {2019}, author = {Farnsworth, JK and Borges, LM and Walser, RD}, title = {Moving Moral Injury Into the Future With Functional Contextualism: A Response to Nash's "Unpacking Two Models for Understanding Moral Injury" (2019).}, journal = {Journal of traumatic stress}, volume = {32}, number = {4}, pages = {633-638}, doi = {10.1002/jts.22429}, pmid = {31356700}, issn = {1573-6598}, mesh = {Humans ; *Military Personnel ; Morals ; *Stress Disorders, Post-Traumatic ; }, abstract = {In his commentary on the Journal of Traumatic Stress special issue on moral injury (Vol. 32, Issue 3), Nash (2019) critiques both Farnsworth's (2019) descriptive-prescriptive framework for differentiating posttraumatic stress disorder (PTSD) from moral injury and Farnsworth, Drescher, Evans, and Walser's (2017) functional contextual definition of moral injury and related concepts. To make his arguments, Nash contrasts these two frameworks with the Navy and Marine Corps Combat Operational Stress Control (COSC) model wherein moral stressors are presumed to cause literal damage to intrapsychic structures. Unfortunately, in drawing his comparisons, Nash makes several misstatements that we feel are important to clarify. We respond to Nash's commentary by first identifying the proper sources for the critiqued frameworks and correctly locate Farnsworth et al.'s functional contextual definition of moral injury within the domain of third-wave cognitive behavioral therapies. We go on to compare and contrast the respective origins of the COSC and functional contextual models, noting important differences in their intended purposes. Next, we defend our model against Nash's critiques by highlighting how a functional contextual approach to moral injury (a) links with evolutionary science, (b) captures multiple levels of analysis, (c) is parsimonious, (d) serves diverse populations, (e) directly informs interventions, (f) promotes moral humility, and (g) decreases stigma while preserving client autonomy. In our conclusion, we recognize the value of the COSC model for its intended purposes while also encouraging deep and respectful dialogue among researchers and clinicians regarding the proposed benefits of the functional contextual model of moral injury.}, } @article {pmid31351509, year = {2019}, author = {Pozharashka, J and Dourmishev, L and Balabanova, M and Vassileva, S and Miteva, L}, title = {Rowell's Syndrome Triggered by Omeprazole.}, journal = {Acta dermatovenerologica Croatica : ADC}, volume = {27}, number = {2}, pages = {124-126}, pmid = {31351509}, issn = {1847-6538}, mesh = {Aged ; Erythema Multiforme/*chemically induced/drug therapy ; Female ; Humans ; Lupus Erythematosus, Cutaneous/*drug therapy ; Omeprazole/*adverse effects ; Proton Pump Inhibitors/*adverse effects ; Syndrome ; }, abstract = {Dear Editor, Rowell's syndrome is a rare disease, characterized by the appearance of erythema multiforme (EM)-like lesions in patients with lupus erythematosus. It was initially reported by Rowell (1) in 1963 and its existence as a separate clinical entity is currently under debate (2,3). A few cases may have been induced by drugs such as systemic antimycotics, antibiotics, anticonvulsants, and more recently proton pump inhibitors (PPIs). CASE REPORT We present the case of a 67-year-old woman with subacute cutaneous lupus erythematosus (SCLE) and EM-like lesions who fulfilled all the criteria for Rowell's syndrome. The patient had lupus arthritis for two years and was treated with oral methylprednisolone 8 mg/day and hydroxychloroquine 200 mg/day. She started receiving 20 mg of omeprazole daily for gastroprotection. The patient also had arterial hypertension with no current treatment, osteoporosis, and an L1 vertebral fracture. The dermatological examination revealed multiple erythematous infiltrated plaques involving mainly the sun-exposed areas (neck, chest, upper back, and shoulders). Cutaneous lesions had an annular or target pattern and a tendency to form hemorrhagic crusts and scales at the margins (Figure 1, A). The mucous membranes were unaffected. Histological examination (hematoxylin and eosin ×200) found epidermal atrophy, vacuolar degeneration of the basal layer, and sparse perivascular lymphocytic infiltrate in the dermis - features corresponding to lupus erythematosus (Figure 2, A). Single eosinophilic necrotic keratinocytes characteristic for erythema multiforme were observed in the epidermis (Figure 2, B). Direct immunofluorescence (IF) from lesional skin showed granular deposits of C3 on the dermo-epidermal junction. Lupus band test from sun-protected, nonlesional skin was negative. On indirect IF a speckled pattern antinuclear antibodies (ANA) with >1:1280 titers were detected. Anti-Ro (>200 U/mL) and anti-La (>200 U/mL) antibodies were also positive. The blood cell count and differential analysis were within reference ranges. The 24-hour urine protein test showed a non-significant proteinuria - 0.36 g/24h. Photo-testing was impossible considering the extent of the skin lesions. The therapeutic approach consisted of increasing the hydroxychloroquine dose to 400 mg/day, substituting PPI with famotidine 20 mg/day p.o. and ceftriaxone 2 g/day for the superinfection with Ps. aeruginosa, which led to a clinical improvement (Figure 1, B). The methylprednisolone dose remained unchanged due to already existing severe adverse effects. DISCUSSION The diagnosis was based on Zeitouni et al.'s classification (4). The three main criteria are as follows: lupus erythematosus, EM-like lesions, and speckled pattern of ANA. Our patient met all three major and one minor criteria, namely the presence of anti-Ro and anti-La antibodies. As for the other minor criteria, RF was negative and no chilblains were found. Although there was a continuous time lapse (more than 1 year) between the initiation of omeprazole intake and the diagnosis of Rowell's syndrome, we suggest that the connection is probable. For instance, the latency differs depending on the incriminated medication in drug induced SCLE. Longer periods are reported for diuretics and calcium blockers, while the time interval is shorter for chemotherapeutic drugs and antimycotics (5). Our suspicions were further confirmed by the fact that the lesions improved promptly within a month after discontinuation of omeprazole and doubling the dose of hydroxychloroquine. PPIs are reported to be a major cause of drug-induced SCLE (6,7). According to Laurinaviciene et al., the most common drugs involved are PPIs, thiazide diuretics, antifungals, chemotherapeutics, statins, and antiepileptics (6). However, very few cases of Rowell's syndrome are found to be drug-related. The culprit drugs include: oral terbinafine (8,9), norfloxacin (10), sodium valproate (11) and esomeprazole (12) (Table 1). CONCLUSION Despite the common clinical and immunological features shared between SCLE, drug-induced SCLE and EM, Rowell's syndrome seems to be a separate entity rather than a coincidental association. Finally, according to our knowledge this case would be the second of Rowell's syndrome due to PPIs.}, } @article {pmid31345113, year = {2019}, author = {Jin, Y and Zhang, LJ}, title = {A Comparative Study of Two Scales for Foreign Language Classroom Enjoyment.}, journal = {Perceptual and motor skills}, volume = {126}, number = {5}, pages = {1024-1041}, doi = {10.1177/0031512519864471}, pmid = {31345113}, issn = {1558-688X}, mesh = {Adolescent ; Emotions ; Factor Analysis, Statistical ; Female ; Humans ; Language ; *Language Arts ; *Learning ; Male ; *Pleasure ; Psychometrics ; *Students ; *Teaching ; }, abstract = {This article reports on a study that tested Jin and Zhang's Chinese version of the Foreign Language Enjoyment Scale for classroom learning through confirmatory factor analysis and compared the resulting scale with Li, Jiang, and Dewaele's 11-item scale. Four hundred five Chinese first language senior high school students of English in years 1-3 participated in this study. We found that Jin and Zhang's version of the Foreign Language Enjoyment Scale could be reduced to a 16-item scale that preserved the same factor structure as the original scale. This revised 16-item scale showed a more solid dimensional division and better psychometric properties than Li et al.'s scale. We discussed our findings in relation to the scale's wider application for improving foreign language teaching and learning.}, } @article {pmid31343896, year = {2020}, author = {Young, AS and Youngstrom, EA and Findling, RL and Van Eck, K and Kaplin, D and Youngstrom, JK and Calabrese, J and Stepanova, E and The Lams Consortium, }, title = {Developing and Validating a Definition of Impulsive/Reactive Aggression in Youth.}, journal = {Journal of clinical child and adolescent psychology : the official journal for the Society of Clinical Child and Adolescent Psychology, American Psychological Association, Division 53}, volume = {49}, number = {6}, pages = {787-803}, pmid = {31343896}, issn = {1537-4424}, support = {R01 MH073953/MH/NIMH NIH HHS/United States ; R01 MH073816/MH/NIMH NIH HHS/United States ; R01 MH073967/MH/NIMH NIH HHS/United States ; R01 MH073801/MH/NIMH NIH HHS/United States ; K23 DA044288/DA/NIDA NIH HHS/United States ; R01 MH066647/MH/NIMH NIH HHS/United States ; }, mesh = {Adolescent ; Aggression/*psychology ; Child ; Female ; Humans ; Impulsive Behavior/*physiology ; Male ; Reproducibility of Results ; }, abstract = {The goal of this study is to develop a rational data-driven definition of impulsive/reactive aggression and establish distinctions between impulsive/reactive aggression and other common childhood problems. This is a secondary analysis of data from Assessing Bipolar: A Community Academic Blend (ABACAB; N = 636, ages 5-18), Stanley Medical Research Institute N = 392, ages 5-17), and the Longitudinal Assessment of Manic Symptoms (LAMS; N = 679, ages 6-12) studies, which recruited youths seeking outpatient mental health services in academic medical centers and community clinics. Following Jensen et al.'s (2007) procedure, 3 judges independently rated items from several widely used scales in terms of assessing impulsive/reactive aggression. Principal components analyses (PCA) modeled structure of the selected items supplemented by items related to mood symptoms, rule-breaking behavior, and hyperactivity/impulsivity to better define the boundaries between impulsive/reactive aggression and other common childhood symptoms. In the rational item selection process, there was good agreement among the 3 experts who rated items as characterizing impulsive/reactive aggression or not. PCA favored 5 dimension solutions in all 3 samples. Across all samples, PCA resulted in rule-breaking behavior, aggression-impulsive/reactive (AIR), mania, and depression dimensions; there was an additional hyperactive/impulsive dimension in the LAMS sample and a self-harm dimension in ABACAB and Stanley samples. The dimensions demonstrated good internal consistency; criterion validity coefficients also showed consistency across samples. This study is a step toward developing an empirically derived nosology of impulsive aggression/AIR. Findings support the validity of the AIR construct, which can be distinguished from manic and depressive symptoms as well as rule-breaking behavior.}, } @article {pmid31342287, year = {2019}, author = {Murphy, HJ and Eklund, MJ and Hill, J and Morella, K and Cahill, JB and Kiger, JR and Twombley, KE and Annibale, DJ}, title = {Early continuous renal replacement therapy during infant extracorporeal life support is associated with decreased lung opacification.}, journal = {Journal of artificial organs : the official journal of the Japanese Society for Artificial Organs}, volume = {22}, number = {4}, pages = {286-293}, pmid = {31342287}, issn = {1619-0904}, mesh = {*Computer Simulation ; Continuous Renal Replacement Therapy/*methods ; Extracorporeal Membrane Oxygenation/*methods ; Heart Failure/complications/*physiopathology/therapy ; Hemodynamics/*physiology ; Humans ; Infant ; Lung/diagnostic imaging ; *Models, Theoretical ; Renal Insufficiency/complications/physiopathology/*therapy ; Reproducibility of Results ; Retrospective Studies ; Time Factors ; }, abstract = {Lung opacification on chest radiography (CXR) is common during extracorporeal life support (ECLS), often resulting from pulmonary edema or inflammation. Concurrent use of continuous renal replacement therapy (CRRT) during ECLS is associated with improved fluid balance and cytokine filtration; through modification of these pathologic states, CRRT may modulate lung opacification observed on CXRs. We hypothesize that early CRRT use during infant ECLS decreases lung opacification on CXR. We conducted a retrospective cohort study comparing CXRs from infants receiving ECLS and early CRRT (n = 7) to matched infants who received ECLS alone (n = 7). The CXR obtained prior to ECLS, all CXRs obtained within the first 72 h of ECLS, and daily CXRs for the remainder of the ECLS course were analyzed. The outcome measure was the degree of opacification, determined by independent assessment of two, blinded pediatric radiologists using a modified Edwards et al.'s lung opacification scoring system (from Score 0: no opacification to Score 5: complete opacification). 220 CXRs were assessed (cases: 93, controls: 127). Inter-rater reliability was established (Cohen's weighted к = 0.74; p < 0.0001, good agreement). At baseline, the mean opacification score difference between cases and controls was 1 point (cases: 1.8, controls 2.8; p = 0.049). Using mixed modeling analysis for repeated measures accounting for differences at baseline, the average overall opacification score was 1.2 points lower in cases than controls (cases: 2.1, controls: 3.3; p < 0.0001). The overall distribution of scores was lower in cases than controls. Early CRRT utilization during infant ECLS was associated with decreased lung opacification on CXR.}, } @article {pmid31299992, year = {2019}, author = {Hladky, SB and Barrand, MA}, title = {Is solute movement within the extracellular spaces of brain gray matter brought about primarily by diffusion or flow? A commentary on "Analysis of convective and diffusive transport in the brain interstitium" Fluids and Barriers of the CNS (2019) 16:6 by L. Ray, J.J. Iliff and J.J. Heys.}, journal = {Fluids and barriers of the CNS}, volume = {16}, number = {1}, pages = {24}, pmid = {31299992}, issn = {2045-8118}, support = {R01 AG054456/AG/NIA NIH HHS/United States ; R01 NS089709/NS/NINDS NIH HHS/United States ; }, mesh = {Biological Transport/physiology ; Brain/*metabolism ; Diffusion ; Extracellular Fluid/*metabolism ; Extracellular Space/*metabolism ; Gray Matter/*metabolism ; Humans ; }, abstract = {Solutes can enter and leave gray matter in the brain by perivascular routes. The glymphatic hypothesis supposes that these movements are a consequence of inward flow along periarterial spaces and an equal outward flow along perivenous spaces. The flow through the parenchyma between periarterial and perivenous spaces is the same as the inflow and the outflow. Ray et al. (Fluids Barriers CNS 16:6, 2019) have investigated how this flow could interact with diffusion using numerical simulations of real-time iontophoresis experiments that monitor the concentrations of tetramethylammonium ions (TMA[+]) injected into the parenchyma via iontophoresis. For this purpose they have devised a description of the parenchyma incorporating perivascular spaces. Their simulations show that superficial flow velocities of about 50 µm min[-1] are needed to produce changes in TMA[+] fluxes comparable to those accounted for by diffusion. In the glymphatic hypothesis the proposed flow through the parenchyma can be estimated from the clearance of solutes that are present in the perivenous outflow at the same concentration as in the interstitial fluid of the parenchyma. Reported clearances are approximately 1 µL min[-1] g[-1]. This flow can be converted to a superficial flow velocity using the area available for the flow, which can be estimated using Ray et al.'s description of the tissue as 40 cm[2] g[-1]. The best available estimate of the flow velocity is thus 0.25 µm min[-1] which is 200 times smaller than the flow that produces effects comparable to diffusion for TMA[+]. Thus it follows in Ray et al.'s description of the parenchyma that diffusion rather than flow accounts for TMA[+] movements. Because the diffusion constant depends only weakly on molecular weight the same is expected to apply even for solutes somewhat larger than serum albumin.}, } @article {pmid31296110, year = {2019}, author = {Ribeiro, AF and Martins Pereira, S and Gomes, B and Nunes, R}, title = {Do patients, families, and healthcare teams benefit from the integration of palliative care in burn intensive care units? Results from a systematic review with narrative synthesis.}, journal = {Palliative medicine}, volume = {33}, number = {10}, pages = {1241-1254}, doi = {10.1177/0269216319862160}, pmid = {31296110}, issn = {1477-030X}, mesh = {Burns/*therapy ; Critical Care/*methods/psychology ; Decision Making ; Delivery of Health Care, Integrated/*organization & administration ; Family/psychology ; Humans ; Palliative Care/*organization & administration/psychology ; Quality of Life ; }, abstract = {BACKGROUND: Burn units are intensive care facilities specialized in the treatment of patients with severe burns. As burn injuries have a major impact in physical, psychosocial, and spiritual health, palliative care can be a strengthening component of integrated care.

AIM: To review and appraise the existing evidence about the integration of palliative care in burn intensive care units with respect to (1) the concept, model and design and (2) the benefits and outcomes of this integration.

DESIGN: A systematic review was conducted following PRISMA guidelines. Protocol registered with PROSPERO (CRD42018111676).

DATA SOURCES: Five electronic databases were searched (PubMed/NLM, Web of Science, MEDLINE/TR, Ovid, and CINAHL/EBSCO) until May 2019. A narrative synthesis of the findings was constructed. Hawker et al.'s tool was used for quality appraisal.

RESULTS: A total of 299 articles were identified, of which five were included for analysis involving a total of 7353 individuals. Findings suggest that there may be benefits from integrating palliative care in burn units, specifically in terms of patients' comfort, decision-making processes, and family care. Multidisciplinary teams may experience lower levels of burden as result of integrating palliative care in burn units.

CONCLUSION: This review reflects the challenging setting of burn intensive care units. Evidence from these articles suggests that the integration of palliative care in burn intensive care units improves patients' comfort, decision-making process, and family care. Further research is needed to better understand how the integration of palliative care in burn intensive care units may be fostered and to identify the outcomes of this integration.}, } @article {pmid31291605, year = {2019}, author = {Suweis, S and Tu, C and Rocha, RP and Zampieri, S and Zorzi, M and Corbetta, M}, title = {Brain controllability: Not a slam dunk yet.}, journal = {NeuroImage}, volume = {200}, number = {}, pages = {552-555}, doi = {10.1016/j.neuroimage.2019.07.012}, pmid = {31291605}, issn = {1095-9572}, mesh = {*Brain ; Humans ; *Nerve Net/physiology ; }, abstract = {In our recent article [1] published in this journal we provide quantitative evidence to show that there are warnings and caveats in the way Gu and collaborators [2] define controllability of brain networks and measure the contribution of each of its nodes. The comment by Pasqualetti et al. [3] confirms the need to go beyond the methodology and approach presented in Gu et al.'s original work. In fact, they recognize that "the source of confusion is due to the fact that assessing controllability via numerical analysis typically leads to ill-conditioned problems, and thus often generates results that are difficult to interpret". This is indeed the first warning we discussed in [1]: our work was not meant to prove that brain networks are not controllable from one node, rather we wished to highlight that the one node controllability framework and all consequent results were not properly justified based on the methodology presented in Gu et al. [2]. We used in our work the same method of Gu et al. not because we believe it is the best methodology, but because we extensively investigated it with the aim of replicating, testing, and extending their results. The warning and caveats we have proposed are the results of this investigation. Indeed, on the basis of our controllability analyses of multiple human brain networks datasets, we concluded: "The λmin(WK) are statistically compatible with zero and thus the associated controllability Gramian cannot be inverted[1]. These results show that it is not possible to infer one node controllability of the brain numerically". Hence both groups agree that one node controllability cannot be inferred numerically.}, } @article {pmid31283471, year = {2019}, author = {Amin, R and Islam, SH and Gope, P and Choo, KR and Tapas, N}, title = {Anonymity Preserving and Lightweight Multimedical Server Authentication Protocol for Telecare Medical Information System.}, journal = {IEEE journal of biomedical and health informatics}, volume = {23}, number = {4}, pages = {1749-1759}, doi = {10.1109/JBHI.2018.2870319}, pmid = {31283471}, issn = {2168-2208}, mesh = {Biometric Identification ; *Computer Security ; Confidentiality ; *Electronic Health Records ; Health Information Exchange/*standards ; Humans ; Telemedicine/*standards ; }, abstract = {Electronic health systems, such as telecare medical information system (TMIS), allow patients to exchange their health information with a medical center/doctor for diagnosis in real time, and across borders. Given the sensitive nature of health information/medical data, ensuring the security of such systems is crucial. In this paper, we revisit Das et al.'s authentication protocol, which is designed to ensure patient anonymity and untraceability. Then, we demonstrate that the security claims are invalid, by showing how both security features (i.e., patient anonymity and untraceability) can be compromised. We also demonstrate that the protocol suffers from smartcard launch attacks. To mitigate such design flaws, we propose a new lightweight authentication protocol using the cryptographic hash function for TMIS. We then analyze the security of the proposed protocol using AVISPA and Scyther, two widely used formal specification tools. The performance analysis demonstrates that our protocol is more efficient than other competing protocols.}, } @article {pmid31280321, year = {2019}, author = {Schneider, H and van der Merwe, M and Marutla, B and Cupido, J and Kauchali, S}, title = {The whole is more than the sum of the parts: establishing an enabling health system environment for reducing acute child malnutrition in a rural South African district.}, journal = {Health policy and planning}, volume = {34}, number = {6}, pages = {430-439}, pmid = {31280321}, issn = {1460-2237}, mesh = {Child ; Child Nutrition Disorders/*prevention & control ; Child, Preschool ; Delivery of Health Care/*organization & administration ; Government Programs/*organization & administration ; Hospital Mortality/trends ; Humans ; Interviews as Topic ; Malnutrition/*prevention & control ; *Maternal-Child Health Services ; Primary Health Care/organization & administration ; Qualitative Research ; Rural Health ; }, abstract = {There is a gap in understanding of how national commitments to child nutrition are translated into sub-national implementation. This article is a mixed methods case study of a rural South African health district which achieved accelerated declines in morbidity and mortality from severe acute malnutrition (SAM) in young children, following a district health system strengthening (HSS) initiative centred on real-time death reporting, analysis and response. Drawing on routine audit data, the declining trends in under-five admissions and in-hospital mortality for SAM over a 5-year period are presented, comparing the district with two others in the same province. Adapting Gillespie et al.'s typology of 'enabling environments' for Maternal and Child Nutrition, and based on 41 in-depth interviews and a follow-up workshop, the article then presents an analysis of how an enabling local health system environment for maternal-child health was established, creating the conditions for achievement of the SAM outcomes. Embedded in supportive policy and processes at national and provincial levels, the district HSS interventions and the manner in which they were implemented produced three kinds of system-level change: knowledge and use of evidence by providers and managers ('ways of thinking'), leadership, participation and coordination ('ways of governing') and inputs and capacity ('ways of resourcing'). These processes mainstreamed responsibility, deepened accountability and triggered new service delivery and organizational practices and mindsets. The article concludes that it is possible to foster enabling district environments for the prevention and management of acute malnutrition, emphasizing the multilevel and simultaneous nature of system actions, where action on system 'software' complements the 'hardware' of HSS interventions, and where the whole is more than the sum of the parts.}, } @article {pmid31269960, year = {2019}, author = {Fujita, N and Matsuoka, S and Koto-Shimada, K and Ikarashi, M and Hazarika, I and Zwi, AB}, title = {Regulation of nursing professionals in Cambodia and Vietnam: a review of the evolution and key influences.}, journal = {Human resources for health}, volume = {17}, number = {1}, pages = {48}, pmid = {31269960}, issn = {1478-4491}, support = {001/WHO_/World Health Organization/International ; a Research Grant for International Health, H29-4//Ministry of Health, Labour and Welfare/International ; }, mesh = {Cambodia ; Economic Development ; Government Regulation ; Health Policy ; Humans ; Licensure, Nursing ; Nurses/*legislation & jurisprudence/*supply & distribution ; Quality of Health Care ; Vietnam ; }, abstract = {BACKGROUND: In 2006, the countries of the Association of Southeast Asian Nations (ASEAN) signed the Mutual Recognition Arrangements (MRA) in relation to nursing services in the region. This agreement was part of a set of policies to promote the free flow of skilled labor among ASEAN members and required mutually acceptable professional regulatory frameworks. This paper presents a narrative review of the literature to (1) describe progress in the development of the regulatory framework for nursing professionals in Cambodia and Vietnam since 2000 and (2) identify key factors, including the MRA, that affect these processes.

METHODS: For document review, policy documents, laws, regulations, and published peer-reviewed and gray literature were reviewed. Data were triangulated and analyzed using a tool developed by adapting McCarthy et al.'s regulatory function framework and covering eight functions (legislation, accreditation of preservice education, competency assessment, registration and licensing system, tools and data flow of registration, scope of practice, continuing professional development, professional misconduct and disciplinary powers).

RESULTS: Cambodia and Vietnam have made remarkable progress in developing their regulatory frameworks for nursing. A number of key influences contributed to the development of nursing regulations, including the signing of the MRA in 2006 and the establishment of the Joint Coordinating Committee on Nursing (AJCCN) in 2007 as key milestones. Macroeconomic and political factors affecting the process were economic growth and an emerging private sector, social demand for quality care and professionalism, global attention to health workforce competencies, the role of development partners, and regular monitoring and mutual learning through AJCCN. A period of incubation enabled countries to develop consensus among stakeholders regarding regulatory arrangements; this trend accelerated after 2010 by bringing national regulatory schemes into conformity with the regional framework. Some similarities in the process (e.g., preservice education first, legislation later) and differences in key actors (e.g., professional councils and the capacity of nursing leaders) were observed in two countries.

CONCLUSION: Further development of the regulatory framework will require strong nursing leadership to sustain achievements and drive continued progress. The adapted tool to assess regulatory capacity works well and may be of value in assessing the development of regulations in the nursing profession.}, } @article {pmid31269255, year = {2019}, author = {Antommaria, AHM}, title = {Relational Potential versus the Parent-Child Relationship.}, journal = {The Hastings Center report}, volume = {49}, number = {3}, pages = {26-27}, doi = {10.1002/hast.1004}, pmid = {31269255}, issn = {1552-146X}, mesh = {Child ; Cognition ; Female ; Humans ; Morals ; *Parent-Child Relations ; *Parenting ; Parents ; }, abstract = {In an article in this issue of the Hastings Center Report, Aaron Wightman and his coauthors attempt to address health care providers' moral distress about acceding to parents' requests to provide life-sustaining medical treatment to children who have profound cognitive disabilities. They propose combining John Arras's relational potential standard and care ethics, and they argue that the capacity for caring relationships can provide an independent moral justification for honoring such requests. This combination is, however, unstable. Wightman et al.'s language of potential and capacity opens the possibility of substantial misinterpretation. They rely on epistemological and prognostic uncertainty to argue that reciprocity and participation may be present in the parent-child relationship even when the child's engagement cannot be observed. The terminology suggests that these are characteristics that can be gained or lost rather than characteristics of being born within certain social practices. In contrast, Eva Feder Kittay illuminates family membership as an important social relation. Her articulation of the independent moral value of parenting stands on its own without being conjoined to Arras's position.}, } @article {pmid31260103, year = {2019}, author = {Dong, C and Zeng, Z and Pu, DK and Wen, QF and Liu, S and Du, MZ and Sun, Y and Gao, YZ and Rao, N and Huang, J and Guo, FB}, title = {CasLocusAnno: a web-based server for annotating cas loci and their corresponding (sub)types.}, journal = {FEBS letters}, volume = {593}, number = {18}, pages = {2646-2654}, doi = {10.1002/1873-3468.13519}, pmid = {31260103}, issn = {1873-3468}, support = {31871335//National Natural Science Foundation of China/International ; //Science Strength Promotion Program of UESTC/International ; }, mesh = {CRISPR-Associated Proteins/*genetics ; Computational Biology/*methods ; Genetic Loci/*genetics ; *Internet ; Molecular Sequence Annotation/*methods ; }, abstract = {In prokaryotes, Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and CRISPR-associated protein (Cas) systems constitute adaptive immune systems against mobile genetic elements (MGEs). Here, we introduce the Markov cluster algorithm (MCL) to Makarova et al.'s method in order to select a more reasonable profile. Additionally, our new Maximum Continuous Cas Subcluster (MCCS) method helps identification of tightly clustered loci. The comparison with two other commonly used programs shows that the method could identify Cas proteins with higher accuracy and lower Additional Prediction Rate (APR). Moreover, we developed a web-based server, CasLocusAnno (http://cefg.uestc.cn/CasLocusAnno), capable of annotating Cas proteins, cas loci and their (sub)types less than ~ 28 s following the whole proteome sequence submission. Its standalone version can be downloaded at https://github.com/RiversDong/CasLocusAnno.}, } @article {pmid31241506, year = {2019}, author = {Mutumba, M and Musiime, V and Mugerwa, H and Nakyambadde, H and Gautam, A and Matama, C and Stephenson, R}, title = {Perceptions of HIV Self-Management Roles and Challenges in Adolescents, Caregivers, and Health Care Providers.}, journal = {The Journal of the Association of Nurses in AIDS Care : JANAC}, volume = {30}, number = {4}, pages = {415-427}, doi = {10.1097/JNC.0000000000000011}, pmid = {31241506}, issn = {1552-6917}, mesh = {Adolescent ; Adult ; Anti-HIV Agents/*therapeutic use ; Caregivers/*psychology ; Child ; Cross-Sectional Studies ; Female ; Focus Groups ; HIV Infections/drug therapy/psychology ; Health Knowledge, Attitudes, Practice ; Health Personnel/*psychology ; Humans ; Male ; Medication Adherence ; Qualitative Research ; Self-Management/methods/*psychology ; Uganda ; Young Adult ; }, abstract = {Self-management of HIV is a desirable goal for the millions of adolescent persons living with HIV (PLWH). Adolescent PLWH continue to experience poor HIV care outcomes, primarily due to poor rates of medication adherence and retention in care, highlighting a need to develop adolescent self-management skills. The aim of our study was to examine adolescent, caregiver, and health care provider perceptions of adolescent PLWH self-management roles, barriers, and facilitators. Swendeman et al.'s self-management framework for chronic diseases guided the analyses. Participant narratives highlighted perceptions of their responsibilities and related challenges with regard to self-management of HIV by adolescents. Our findings highlighted the complexity of HIV self-management for adolescents and underscored the need for multifaceted programs to strengthen adolescent-caregiver-health care provider partnerships in order to improve adolescent PLWH health and wellbeing.}, } @article {pmid31237440, year = {2020}, author = {Kinney, L and O'Hare, D}, title = {Responding to an Unexpected In-Flight Event: Physiological Arousal, Information Processing, and Performance.}, journal = {Human factors}, volume = {62}, number = {5}, pages = {737-750}, doi = {10.1177/0018720819854830}, pmid = {31237440}, issn = {1547-8181}, mesh = {*Accidents, Aviation ; Adolescent ; Adult ; Cognition ; *Computer Simulation ; Female ; Humans ; Male ; Middle Aged ; Pilots/*psychology ; *Stress, Psychological ; *Task Performance and Analysis ; Young Adult ; }, abstract = {OBJECTIVE: The study was designed to investigate whether a simulated unexpected abnormal flight event can lead to startle and explore differences in behavioral responses between expected and unexpected abnormal flight events.

BACKGROUND: Recent research suggests startle (an autonomic response to an acute stimulus) following unexpected abnormal flight events can impact pilot performance and can increase the probability of a negative outcome following the event.

METHOD: Information processing, physiological measures, and performance differences between responses to expected and unexpected flight events were compared. General aviation (GA) pilots flew a series of flights in a fixed-base flight simulator including two experimental flights which included an unexpected and an expected, engine failure. During the flights, heart rate, eye tracking, and flight data were recorded.

RESULTS: During the unexpected engine failure, pilots showed greater increases in heart rate and pupil dilation. Significant differences in scanning were evident with fewer areas scanned following the unexpected event. During the unexpected engine failure, performance was impaired when compared to the expected events. However, poor performance was not associated with higher levels of arousal.

CONCLUSION: The study provides an empirical demonstration of impaired pilot response to unexpected events with associated symptoms consistent with the induction of startle. The present research builds on Landman et al.'s conceptual model of startle and surprise.

APPLICATION: Standardized training protocols may not adequately prepare pilots to deal with the unexpected effects of startle in real-world encounters. Introducing greater variety into training events may be useful. The effects of startle in disrupting well-trained responses may also occur in areas other than aviation where critical events may occur unexpectedly or present in an unfamiliar manner.}, } @article {pmid31216864, year = {2019}, author = {Ferguson, RH and Falcomata, TS and Ramirez-Cristoforo, A and Vargas Londono, F}, title = {An Evaluation of the Effects of Varying Magnitudes of Reinforcement on Variable Responding Exhibited by Individuals With Autism.}, journal = {Behavior modification}, volume = {43}, number = {6}, pages = {774-789}, doi = {10.1177/0145445519855615}, pmid = {31216864}, issn = {1552-4167}, mesh = {Adolescent ; Autistic Disorder/complications/*therapy ; Child ; Child, Preschool ; Communication Disorders/complications/*therapy ; Female ; Humans ; Male ; Reinforcement Schedule ; *Reinforcement, Psychology ; Speech Therapy/*methods ; }, abstract = {Interventions aimed at increasing communicative response variability hold particular importance for individuals with autism spectrum disorders (ASD). Several procedures have been demonstrated in the applied and translational literature to increase response variability. However, little is known about the relationship between reinforcer magnitude and response variability. In the basic literature, Doughty, Giorno, and Miller evaluated the effects of reinforcer magnitude on behavioral variability by manipulating reinforcer magnitude across alternating relative frequency threshold contingencies, with results suggesting that larger reinforcers induced repetitive responding. The purpose of this study was to translate Doughty et al.'s findings to evaluate the relative effects of different magnitudes of reinforcement on communicative response variability in children with ASD. A Lag 1 schedule of reinforcement was in place during each condition within an alternating treatments design. Magnitudes of reinforcement contingent on variable communicative responding were manipulated across the two conditions. Inconsistent with basic findings, the results showed higher levels of variable communicative responding associated with the larger magnitude of reinforcement. These outcomes may have potential implications for interventions aimed at increasing response variability in individuals with ASD, as well as future research in this area.}, } @article {pmid31208861, year = {2020}, author = {Gonçalves, RV and Fonseca, ST and Araújo, PA and Araújo, VL and Barboza, TM and Martins, GA and Mancini, MC}, title = {Identification of gait events in children with spastic cerebral palsy: comparison between the force plate and algorithms.}, journal = {Brazilian journal of physical therapy}, volume = {24}, number = {5}, pages = {392-398}, pmid = {31208861}, issn = {1809-9246}, mesh = {Adolescent ; Algorithms ; *Cerebral Palsy ; Child ; Child, Preschool ; Cross-Sectional Studies ; Female ; Foot ; Gait/*physiology ; Gait Disorders, Neurologic/diagnosis ; Humans ; Male ; }, abstract = {OBJECTIVE: To compare the gait event identification of five algorithms recommended in the literature with those provided by force plate (gold standard) in children with unilateral or bilateral spastic cerebral palsy (SCP).

METHODS: This was a cross-sectional study of the gait of three girls and four boys with a mean age of 8.6±4.7 years. Four children had unilateral SCP with an equinus gait pattern, and the remaining three children exhibited bilateral SCP with a slide/drag gait pattern. Kinematic and kinetic gait data were collected during barefoot walking at a comfortable speed. From a total of 202 steps, the detection of 202 foot-strike (FS) and 194 toe-off (TO) events by each algorithm was compared with the detection of these same events by the force plate. The error between the events detected by the algorithms and those detected by the force plate was determined in milliseconds. Repeated measures ANOVA was used to compare the errors among the algorithms.

RESULTS: The algorithm reported by Ghoussayni et al. showed the best performance in all situations, except for the identification of FS events on the unaffected side in children with unilateral SCP. For these events, the algorithms reported by Desailly et al. and Zeni et al. showed the best performance.

CONCLUSION: Ghoussayni et al.'s algorithm can be used to detect gait events in children with SCP when a force plate is not available.}, } @article {pmid31204633, year = {2019}, author = {Wang, Z and Wu, X and Dai, W and Kaminga, AC and Wu, X and Pan, X and Liu, Z and Wen, S and Hu, S and Liu, A}, title = {The Prevalence of Posttraumatic Stress Disorder Among Survivors After a Typhoon or Hurricane: A Systematic Review and Meta-Analysis.}, journal = {Disaster medicine and public health preparedness}, volume = {13}, number = {5-6}, pages = {1065-1073}, doi = {10.1017/dmp.2019.26}, pmid = {31204633}, issn = {1938-744X}, mesh = {Adult ; *Cyclonic Storms ; Humans ; Prevalence ; Stress Disorders, Post-Traumatic/*diagnosis/epidemiology/psychology ; Survivors/*psychology ; }, abstract = {Posttraumatic stress disorder (PTSD) is a psychological disorder, which could be caused by traumatic events. The prevalence of PTSD among survivors after a typhoon or hurricane varied widely. Therefore, this study aimed to determine a combined prevalence of PTSD among survivors after a typhoon or hurricane. A systematic search of literature was performed in the 3 English databases: PubMed (National Library of Medicine, Bethesda, MD), ISI Web of Science (Thomson Reuters, New York, NY), and Embase (Elsevier, Amsterdam, Netherlands). Also, a similar search was performed in the 2 Chinese databases such as Chinese National Knowledge Infrastructure and WanFang. Loney et al.'s criteria were used to evaluate the quality of the selected articles for this study. The combined prevalence of PTSD among the study population was estimated using the Freeman-Tukey double arcsine transformation method. Subgroup analyses and a meta-regression analysis were carried out to explore the origin of heterogeneity. Thirty-nine eligible articles were included in this study. They comprised 43 123 typhoon and hurricane survivors of which 9373 were diagnosed with PTSD. The combined prevalence of PTSD among this population was 17.81%. Subgroup analyses revealed that the combined prevalence of PTSD related to typhoon and hurricane Categories 5, 4, and 2 showing a corresponding decreasing tendency. About 18% of people who experienced a severe typhoon or hurricane develop PTSD with the prevalence decreasing with reduced severity of the typhoon or hurricane.}, } @article {pmid31204538, year = {2019}, author = {Al Maqbali, M and Hughes, C and Gracey, J and Rankin, J and Dunwoody, L and Hacker, E}, title = {Quality assessment criteria: psychometric properties of measurement tools for cancer related fatigue.}, journal = {Acta oncologica (Stockholm, Sweden)}, volume = {58}, number = {9}, pages = {1286-1297}, doi = {10.1080/0284186X.2019.1622773}, pmid = {31204538}, issn = {1651-226X}, mesh = {Fatigue/*diagnosis/etiology ; Female ; Guidelines as Topic/standards ; Humans ; Male ; Neoplasms/*complications ; Psychometrics ; Quality Assurance, Health Care ; Quality of Life ; Reproducibility of Results ; *Severity of Illness Index ; }, abstract = {Background: Fatigue is a common and distressing cancer symptom that negatively affects the quality of life. Many scales have been developed to assess cancer-related fatigue. The properties of the scales vary in terms of dimensionality, reliability, validity, length and method of administration. Insufficient of psychometric properties may affect the accuracy of scales findings, that may lead result obtained questionable. The main objective of this review was to conduct a quality assessment of the psychometric properties of cancer-related fatigue scales to identify appropriate scales that could be used in research and clinical practice. Method: A systematic search was carried out to identify validated scales that measure cancer-related fatigue. Five databases were searched: CINAHL, MEDLINE, EMBASE, PsycINFO, Cochrane Library. This review was conducted following the PRISMA and Terwee et al.'s quality assessment guidelines to evaluate the psychometric properties of the studies. Result: Seventy-one different studies published between 1970 and 2018 met the inclusion criteria. Twenty-five scales were identified. Of these, eighteen were multidimensional and seven were uni-dimensional, containing between 4 and 72 items. Reliability and/or validity information was missing for many scales. Four scales met the quality assessment criteria and were reported as the most appropriate for measuring fatigue in cancer patients. Conclusion: Further psychometric testing is required for other scales. Developing a universally-defined tool kit for the assessment of cancer-related fatigue may help clarify the concept of fatigue and promote a systematic approach to fatigue measurement.}, } @article {pmid31193807, year = {2019}, author = {Namujwiga, T and Nakitende, I and Kellett, J and Opio, M and Lumala, A and , }, title = {Prognostic performance of ECG abnormalities compared to vital signs in acutely ill patients in a resource-poor hospital in Uganda.}, journal = {African journal of emergency medicine : Revue africaine de la medecine d'urgence}, volume = {9}, number = {2}, pages = {64-69}, pmid = {31193807}, issn = {2211-4203}, abstract = {BACKGROUND: There are few reports of electrocardiogram (ECG) findings and their prognostic value in acutely ill patients admitted to low resource hospitals in sub-Saharan Africa.

METHODS: We undertook an observational study of acutely ill medical patients admitted to a low-resource hospital in Uganda. Vital signs were used to calculate the National Early Warning Score (NEWS), and all ECGs were assessed using Tan et al.'s scoring system as described in Clin Cardiol 2009;32:82-86.

RESULTS: There were 1361 ECGs performed, covering 68% of all acutely ill medical patients admitted to the hospital during the study. The most common ECG abnormality was a prolonged QTc interval (42% of all patients) and left ventricular hypertrophy (13.5%). Compared to the 519 patients (38%) with no Tan score abnormality, the 842 (62%) patients with one or more abnormalities were more likely to die in hospital (OR = 2.82; CI95% = 1.50-5.36) and within 30 days of discharge (OR = 2.46; CI95% = 1.50-4.08). There was no relationship between age and mortality; however, after adjustment by logistic regression, any NEWS ≥1 on admission, a Tan score of ≥1, and male sex all remained clinically significant predictors of both in-hospital and 30-day mortality.

DISCUSSION: The majority of acutely ill medical patients admitted in a low-resource hospital in sub-Saharan Africa had ECG abnormalities, of which prolonged QTc and left ventricular hypertrophy were most common. Those with any Tan score abnormality were twice as likely to die as those without an abnormality.}, } @article {pmid31190382, year = {2019}, author = {Hanquinet, L}, title = {Culture matters: comments on Chan's and Flemmen et al.'s contributions to the field of cultural participation.}, journal = {The British journal of sociology}, volume = {70}, number = {3}, pages = {898-905}, doi = {10.1111/1468-4446.12642}, pmid = {31190382}, issn = {1468-4446}, } @article {pmid35519333, year = {2019}, author = {Li, X and Bian, R and Wang, J and Wang, X and Ma, J and Ma, G and Sui, H and He, L}, title = {Recovery of extra-heavy oil and minerals from carbonate asphalt rocks by reactive extraction.}, journal = {RSC advances}, volume = {9}, number = {25}, pages = {14372-14381}, pmid = {35519333}, issn = {2046-2069}, abstract = {Quite different from the Canadian oil sands, the Indonesian asphalt rocks proved to be carbonate unconventional oil ores. The strong interactions between asphalt and minerals make water-based extraction work poorly in separating this kind of ore. Herein, a reactive extraction process has been proposed to separate asphalt and mineral solids from the ores through dissolving the mineral solids (i.e., carbonate minerals, metal oxides, etc.) by acids (formic acid). It is evidenced that most of the asphalt could be recovered and collected on the top of the solution by generated CO2. What's more, the unreacted formic acid could be recycled in this process. The dissolved metal ions could be efficiently recovered to obtain different by-products by chemical settling and crystallization. The amount of residual solids settled at the bottom of the reactor is very small. Further tests show that the reaction efficiency is highly dependent on the operational conditions, including temperature, stirring rate, acid dosage, concentration of acid, etc. It is also found that the reaction could allow minerals to be redistributed in different phases. Although some metal elements could be dissolved into solution, elements such as Fe, Al, S, Si, and Ti are observed to accumulate in asphalt froth. In addition to reacting with minerals, formic acid is also found to reduce asphalt viscosity. This reduction improves the reaction efficiency. Based on primary evaluations, the above findings suggest that the reactive extraction would be a potential process to exploit the Indonesian asphalt rocks (or other similar ores) due to its full recovery to all materials.}, } @article {pmid34706486, year = {2018}, author = {Simões, TR and Caldwell, MW and Palci, A and Nydam, RL}, title = {Giant taxon-character matrices II: a response to Laing et al. (2017).}, journal = {Cladistics : the international journal of the Willi Hennig Society}, volume = {34}, number = {6}, pages = {702-707}, doi = {10.1111/cla.12231}, pmid = {34706486}, issn = {1096-0031}, support = {238458//Natural Sciences and Engineering Research Council of Canada/ ; 412275//Natural Sciences and Engineering Research Council of Canada/ ; //Faculty of Science Chairs Research Allowance/ ; }, abstract = {The trend towards big data analyses in evolutionary biology has been observed in phylogenetics via the assembly of giant datasets composed of genomic and phenotypic data. We recently (Simões et al., 2017. Giant taxon-character matrices: Quality of character constructions remains critical regardless of size. Cladistics 33, 198-219) presented a critique of the phylogenetic character concepts used in current morphological datasets, with the caution that giant datasets did not obviate the empirical requirement of rigor in character construction. Laing et al. (2017. Giant taxon-character matrices: The future of morphological systematics. Cladistics, https://doi.org/10.1111/cla.12197) have since argued that we had 'suggested' that large datasets inherently contain flawed characters, and that we had presented a substandard methodology of phylogenetic analysis. Laing et al. concluded by discussing their approach to phylogenetic signal, total evidence and the inevitability of large datasets. We here reply to Laing et al. by reviewing what we actually wrote regarding dataset size, characters and methodology. We show that Laing et al.'s. central premise is unsupported, thus characterizing a Straw Man argument, and deeply misrepresents our original study. In part two, we discuss total evidence and phylogenetic signal issues raised by Laing et al. that are of major consequence to the appropriate construction of large morphological datasets.}, } @article {pmid31517207, year = {2018}, author = {Rutten, I and Voorspoels, W and Steegen, S and Kuppens, P and Vanpaemel, W}, title = {Depressive Symptoms and Category Learning: A Preregistered Conceptual Replication Study.}, journal = {Journal of cognition}, volume = {1}, number = {1}, pages = {34}, pmid = {31517207}, issn = {2514-4820}, abstract = {We present a fully preregistered, high-powered conceptual replication of Experiment 1 by Smith, Tracy, and Murray (1993). They observed a cognitive deficit in people with elevated depressive symptoms in a task requiring flexible analytic processing and deliberate hypothesis testing, but no deficit in a task assumed to require more automatic, holistic processing. Specifically, they found that individuals with depressive symptoms showed impaired performance on a criterial-attribute classification task, requiring flexible analysis of the attributes and deliberate hypothesis testing, but not on a family-resemblance classification task, assumed to rely on holistic processing. While deficits in tasks requiring flexible hypothesis testing are commonly observed in people diagnosed with a major depressive disorder, these deficits are much less commonly observed in people with merely elevated depressive symptoms, and therefore Smith et al.'s (1993) finding deserves further scrutiny. We observed no deficit in performance on the criterial-attribute task in people with above average depressive symptoms. Rather, we found a similar difference in performance on the criterial-attribute versus family-resemblance task between people with high and low depressive symptoms. The absence of a deficit in people with elevated depressive symptoms is consistent with previous findings focusing on different tasks.}, } @article {pmid32158019, year = {2018}, author = {Bindler, R}, title = {Comment on "Next-Generation Ice Core Technology Reveals True Minimum Natural Levels of Lead (Pb) in the Atmosphere: Insights From the Black Death" by More et al.}, journal = {GeoHealth}, volume = {2}, number = {5}, pages = {155-161}, pmid = {32158019}, issn = {2471-1403}, abstract = {Over the past four decades numerous studies of lake sediment, marine sediment, and peat from sites in close proximity to mining or metallurgical centers and in remote locations have detailed local and regional histories of lead (Pb) pollution in Europe. Contrary to More et al.'s (2017, https://doi.org/10.1002/2017GH000064) claim that "previous assumptions about preindustrial "natural" background lead levels in the atmosphere have been misleading," these studies have clearly shown that true natural background conditions occurred more than 2,500 or even 3,500 years ago, and Pb pollution has proceeded uninterrupted since. The implications of this have been discussed within the context of environmental policy, for example, European Water Framework Directive. Though these records reflect a common European narrative of mining, metallurgy, and pollution, each reflects a combination of local and regional events, leading to differences in the timing and intensity of changes in each Pb record. No one record-ice or otherwise-fully represents the three millennia Pb pollution history in Europe. While the resolution of the ice record is impressive, there are questions about its interpretation. First, the authors discount local and regional Pb sources, whereas there is a close connection between the mining history in an area 40 km from the glacier and changes in a nearby lake Pb record; second, significant changes in ice chemistry cooccurring with the lowest Pb values are overlooked. A sharp increase in Ca/Fe ratios occurs precisely with the steepest Pb declines during the Black Death and mid-1400s, suggesting additional processes influencing the Pb record.}, } @article {pmid31294393, year = {2018}, author = {Mathias, H and van Zanten, SV and Kits, O and Heisler, C and Jones, J}, title = {Patient-ly Waiting: A Review of Patient-Centered Access to Inflammatory Bowel Disease Care in Canada.}, journal = {Journal of the Canadian Association of Gastroenterology}, volume = {1}, number = {1}, pages = {26-32}, pmid = {31294393}, issn = {2515-2092}, abstract = {Canada has one of the highest prevalence estimates of inflammatory bowel disease (IBD) in the world. Like other chronic illnesses, access to specialist care is required for disease management. Traditionally, access to care is evaluated through wait times (actual access); however, new patient-oriented definitions of access (perceived access) highlight other equally important facets of access to care (e.g., appropriateness). Aim: How does access to gastroenterology speciality care influence disease-related outcomes for IBD patients in Canada? A comprehensive literature review was undertaken. Cochrane, PubMed and CINHAL databases were searched for peer-reviewed English language articles published between 2006 and 2016. Inclusion/exclusion criteria focussed on access to IBD care in Canada. Included articles were classified using Levesque et al.'s patient-centered access framework (e.g., affordability, accessibility, appropriateness, acceptability, availability and accommodation). Eight articles were found, including six which addressed patient-centered access. Most of the articles addressed issues of availability (e.g., wait times), appropriateness and affordability. Only one article addressed approachability and acceptability of IBD care. All articles emphasized a need for greater patient-centered measures (e.g., multidisciplinary clinics) with a goal to improve patient access and, ultimately, patient outcomes. Understanding patient-centered access to IBD care is important for managing IBD and improving patient outcomes. Literature examining access to gastroenterology services is limited. Increased investment in patient-oriented research should be made to better understand the relationship between access to specialist care and patient outcomes.}, } @article {pmid34724761, year = {2017}, author = {Simmons, MP}, title = {Mutually exclusive phylogenomic inferences at the root of the angiosperms: Amborella is supported as sister and Observed Variability is biased.}, journal = {Cladistics : the international journal of the Willi Hennig Society}, volume = {33}, number = {5}, pages = {488-512}, doi = {10.1111/cla.12177}, pmid = {34724761}, issn = {1096-0031}, abstract = {Identifying the extant sister group to the remaining angiosperms has been a subject of long debate, for which the primary currently competing hypotheses are that Amborella alone is sister or that the clade (Amborella, Nymphaeales) is sister. Both Xi et al. (Syst. Biol., 2014, 63, 919) and Goremykin et al. (Syst. Biol., 2015, 64, 879) identified Amborella as sister in concatenation-based phylogenetic analyses of their 310 nuclear genes and 78 plastid genes, respectively. But after application of Observed Variability-based character subsampling, both papers reported the clade (Amborella, Nymphaeales) as sister. Hence alternative character-sampling strategies may produce highly supported yet mutually exclusive phylogenetic inferences when applied to nuclear and plastid genomic data sets. Edwards et al. (Mol. Phylogenet. Evol., 2016, 94, 447) defended Observed Variability and the (Amborella, Nymphaeales) hypothesis. In this study I respond to Edwards et al.'s (Mol. Phylogenet. Evol., 2016, 94, 447) criticisms of Simmons and Gatesy (Mol. Phylogenet. Evol., 2015, 91, 98) and use Edwards et al.'s (Mol. Phylogenet. Evol., 2016, 94, 447) and Goremykin et al.'s (Syst. Biol., 2015, 64, 879) own data to demonstrate that the best-supported phylogenetic hypothesis is that Amborella alone is sister and that the competing evidence in favour of the (Amborella, Nymphaeales) hypothesis is caused primarily by methodological artifacts (biased character deletion by Observed Variability, MP-EST and STAR generally not being robust to the highly divergent and mis-rooted gene trees that were used).}, } @article {pmid32668530, year = {2016}, author = {Bagnardi, V and Botteri, E and La Vecchia, C}, title = {Reply to the letter to the editor 'Erroneous conclusions about the association between light alcohol drinking and the risk of cancer: comments on Bagnardi et al.'s meta-analysis, by S.-K. Myung'.}, journal = {Annals of oncology : official journal of the European Society for Medical Oncology}, volume = {27}, number = {11}, pages = {2139-2140}, doi = {10.1093/annonc/mdw295}, pmid = {32668530}, issn = {1569-8041}, } @article {pmid35596407, year = {2015}, author = {Jho, Y and Landy, J and Pincus, PA}, title = {Charge Renormalization for Ellipsoidal Macroions.}, journal = {ACS macro letters}, volume = {4}, number = {6}, pages = {640-644}, doi = {10.1021/acsmacrolett.5b00252}, pmid = {35596407}, issn = {2161-1653}, abstract = {We study the problem of counterion condensation for ellipsoidal macroions, a geometry well-suited for modeling liquid crystals, anisotropic vesicles, and polymers. We find that the ions within an ellipsoid's condensation layer are relatively unrestricted in their motions, and consequently work to establish a quasi-equipotential at its surface. This simplifies the application of Alexander et al.'s procedure, enabling us to obtain accurate analytic estimates for the critical valence of a general ellipsoid in the weak screening limit. Interestingly, we find that the critical valence of an eccentric ellipsoid is always larger than that of the sphere of equal volume, implying that counterion condensation provides a force resisting the deformation of spherical macroions. This contrasts with a recent study of flexible spherical macroions, which observed a preference for deformation into flattened shapes when considering only linear effects. Our work suggests that the balance of these competing forces might alter the nature of the transition.}, } @article {pmid33430542, year = {2005}, author = {Wagner, L and Carey, S}, title = {12-Month-Old Infants Represent Probable Endings of Motion Events.}, journal = {Infancy : the official journal of the International Society on Infant Studies}, volume = {7}, number = {1}, pages = {73-83}, doi = {10.1207/s15327078in0701_6}, pmid = {33430542}, issn = {1532-7078}, abstract = {This experiment investigated 12-month-old infants' ability to link an event's beginning to its probable ending. Following Csibra, Biro, Koos, and Gergely (2003), infants were habituated to a simple chasing event involving animated balls, and at test saw 2 possible endings: either 1 ball caught the other or failed to do so. Two controls were added to the previous work. First, the total amount of motion was controlled in the test endings; second, the endings were paired with a nonchasing beginning to ensure that behavior at test reflected representation of the event beginning itself. The results replicated Csibra et al.'s finding that infants look longer at the noncatching ending following the chasing beginning; moreover, infants showed no preference for either ending following the no-chasing beginning. This study supports the claim that infants can calculate the rational ending of a goal-directed motion event.}, } @article {pmid34902941, year = {1999}, author = {Goloboff, PA}, title = {Analyzing Large Data Sets in Reasonable Times: Solutions for Composite Optima.}, journal = {Cladistics : the international journal of the Willi Hennig Society}, volume = {15}, number = {4}, pages = {415-428}, doi = {10.1111/j.1096-0031.1999.tb00278.x}, pmid = {34902941}, issn = {1096-0031}, abstract = {New methods for parsimony analysis of large data sets are presented. The new methods are sectorial searches, tree-drifting, and tree-fusing. For Chase et al.'s 500-taxon data set these methods (on a 266-MHz Pentium II) find a shortest tree in less than 10 min (i.e., over 15,000 times faster than PAUP and 1000 times faster than PAUP*). Making a complete parsimony analysis requires hitting minimum length several times independently, but not necessarily all "islands" for Chase et al.'s data set, this can be done in 4 to 6 h. The new methods also perform well in other cases analyzed (which range from 170 to 854 taxa).}, } @article {pmid34920626, year = {1996}, author = {Farris, JS}, title = {NAMES AND ORIGINS.}, journal = {Cladistics : the international journal of the Willi Hennig Society}, volume = {12}, number = {3}, pages = {263-264}, doi = {10.1111/j.1096-0031.1996.tb00013.x}, pmid = {34920626}, issn = {1096-0031}, abstract = {- Contrary to the impression given by Trueman (1996), Bremer (1988) introduced what is now called Bremer support; Faith (1991) did not. Neither did Mishler and Donoghue (1991). Attaching Faith and Cranston's (1991) acronym PTP to Archie's (1989) test does not help make the authorship clear, and the same applies to Källersjö et al.'s (1992) total support test.}, } @article {pmid31183117, year = {2019}, author = {IJzerman, H and Denissen, JJA}, title = {Social value orientation and attachment: a replication and extension of Van Lange et al. (1997).}, journal = {Royal Society open science}, volume = {6}, number = {4}, pages = {181575}, pmid = {31183117}, issn = {2054-5703}, abstract = {We report a replication and extension of a finding from Studies 1 and 2 of Van Lange et al.'s influential paper (Van Lange et al. 1997 J. Pers. Soc. Psychol. 73, 733-746. (doi:10.1037/0022-3514.73.4.733)), which showed an association between Social Value Orientation (SVO) and attachment security. We report a close replication but with measures of attachment that are considered superior in comparison to measures used by Van Lange et al., due to subsequent psychometric improvements. Psychometric analyses indeed showed that our attachment measures were reliable and valid, demonstrating theoretically predicted associations with other outcomes. With a sample (N = 879) sufficiently large to detect d = 0.19 (and larger than the original N = 573), we failed to replicate the effect. Based on the available evidence, we interpret as there being no evidence for the link between attachment security and Social Value Orientation, but further replication research that uses solid measures and large samples can provide more definite conclusions about the association between attachment and SVO.}, } @article {pmid31182592, year = {2019}, author = {Shover, CL and Davis, CS and Gordon, SC and Humphreys, K}, title = {Association between medical cannabis laws and opioid overdose mortality has reversed over time.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {26}, pages = {12624-12626}, pmid = {31182592}, issn = {1091-6490}, support = {T32 DA035165/DA/NIDA NIH HHS/United States ; }, mesh = {Drug Overdose/epidemiology/*mortality ; Drug Utilization/legislation & jurisprudence/statistics & numerical data ; Humans ; Legislation, Drug/*statistics & numerical data ; Medical Marijuana/*administration & dosage ; Opioid Epidemic/*mortality/statistics & numerical data ; United States ; }, abstract = {Medical cannabis has been touted as a solution to the US opioid overdose crisis since Bachhuber et al. [M. A. Bachhuber, B. Saloner, C. O. Cunningham, C. L. Barry, JAMA Intern. Med. 174, 1668–1673] found that from 1999 to 2010 states with medical cannabis laws experienced slower increases in opioid analgesic overdose mortality. That research received substantial attention in the scientific literature and popular press and served as a talking point for the cannabis industry and its advocates, despite caveats from the authors and others to exercise caution when using ecological correlations to draw causal, individual-level conclusions. In this study, we used the same methods to extend Bachhuber et al.’s analysis through 2017. Not only did findings from the original analysis not hold over the longer period, but the association between state medical cannabis laws and opioid overdose mortality reversed direction from −21% to +23% and remained positive after accounting for recreational cannabis laws. We also uncovered no evidence that either broader (recreational) or more restrictive (low-tetrahydrocannabinol) cannabis laws were associated with changes in opioid overdose mortality. We find it unlikely that medical cannabis—used by about 2.5% of the US population—has exerted large conflicting effects on opioid overdose mortality. A more plausible interpretation is that this association is spurious. Moreover, if such relationships do exist, they cannot be rigorously discerned with aggregate data. Research into therapeutic potential of cannabis should continue, but the claim that enacting medical cannabis laws will reduce opioid overdose death should be met with skepticism.}, } @article {pmid31171371, year = {2019}, author = {Donnelly, CJ and Alexander, CF and Stannage, K and Reid, S}, title = {A commentary on Kalkman et al.'s letter to the editor regarding Alexander et al. (2019): "Children with cerebral palsy have larger in-vivo and linearly scaled Achilles tendon moment arms than typically developing children".}, journal = {Journal of biomechanics}, volume = {92}, number = {}, pages = {178-180}, doi = {10.1016/j.jbiomech.2019.04.047}, pmid = {31171371}, issn = {1873-2380}, mesh = {*Achilles Tendon ; Ankle Joint ; *Cerebral Palsy ; Child ; Humans ; Muscle, Skeletal ; }, } @article {pmid31171014, year = {2019}, author = {Wiltsey Stirman, S and Baumann, AA and Miller, CJ}, title = {The FRAME: an expanded framework for reporting adaptations and modifications to evidence-based interventions.}, journal = {Implementation science : IS}, volume = {14}, number = {1}, pages = {58}, pmid = {31171014}, issn = {1748-5908}, support = {U24 HL136790/HL/NHLBI NIH HHS/United States ; U01 HL133994/HL/NHLBI NIH HHS/United States ; 5R25MH08091607/MH/NIMH NIH HHS/United States ; QUE 15-289/HX/HSRD VA/United States ; R01 HG009351/HG/NHGRI NIH HHS/United States ; R01 MH106506/MH/NIMH NIH HHS/United States ; UL1TR00234/MH/NIMH NIH HHS/United States ; }, mesh = {*Clinical Coding ; Clinical Competence/standards ; Delivery of Health Care/*standards ; *Evidence-Based Medicine ; Humans ; Organizational Culture ; Psychotherapy/*standards ; }, abstract = {BACKGROUND: This paper describes the process and results of a refinement of a framework to characterize modifications to interventions. The original version did not fully capture several aspects of modification and adaptation that may be important to document and report. Additionally, the earlier framework did not include a way to differentiate cultural adaptation from adaptations made for other reasons. Reporting additional elements will allow for a more precise understanding of modifications, the process of modifying or adapting, and the relationship between different forms of modification and subsequent health and implementation outcomes.

DISCUSSION: We employed a multifaceted approach to develop the updated FRAME involving coding documents identified through a literature review, rapid coding of qualitative interviews, and a refinement process informed by multiple stakeholders. The updated FRAME expands upon Stirman et al.'s original framework by adding components of modification to report: (1) when and how in the implementation process the modification was made, (2) whether the modification was planned/proactive (i.e., an adaptation) or unplanned/reactive, (3) who determined that the modification should be made, (4) what is modified, (5) at what level of delivery the modification is made, (6) type or nature of context or content-level modifications, (7) the extent to which the modification is fidelity-consistent, and (8) the reasons for the modification, including (a) the intent or goal of the modification (e.g., to reduce costs) and (b) contextual factors that influenced the decision. Methods of using the framework to assess modifications are outlined, along with their strengths and weaknesses, and considerations for research to validate these measurement strategies.

CONCLUSION: The updated FRAME includes consideration of when and how modifications occurred, whether it was planned or unplanned, relationship to fidelity, and reasons and goals for modification. This tool that can be used to support research on the timing, nature, goals and reasons for, and impact of modifications to evidence-based interventions.}, } @article {pmid31163065, year = {2019}, author = {Izzo, VA and Donati, MA and Ramat, S and Primi, C}, title = {Impulse control disorders in Parkinson's disease: A systematic review on the psychometric properties of the existing measures.}, journal = {PloS one}, volume = {14}, number = {6}, pages = {e0217700}, pmid = {31163065}, issn = {1932-6203}, mesh = {Disruptive, Impulse Control, and Conduct Disorders/*complications ; Humans ; Parkinson Disease/*complications ; *Psychometrics ; Publications ; }, abstract = {BACKGROUND: A significant percentage of patients suffering from Parkinson's Disease (PD) experience Impulse Control Disorders (ICDs), contributing to reduced quality of life. As they can be managed by reducing the dopamine dosage, the detection of their presence is crucial for PD treatment plan. Nevertheless, they tend to be under-recognized in clinical practice, since routine screening is not common-despite existing instruments that may support clinicians. This work presents a systematic review on the psychometric properties of instruments measuring ICDs in PD, to test whether clinicians dispose of valid tools that may help them in clinical assessment.

METHOD: A systematic literature search in three databases (EMBASE, MEDLINE, and PsycINFO) was conducted. Quality of the instruments' psychometric properties was evaluated with Terwee et al.'s criteria, and methodological quality of the studies was evaluated with the COSMIN Checklist.

RESULTS: Ten studies examining seven instruments were selected. The Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease (QUIP) and the Ardouin Scale of Behavior in Parkinson's Disease (ASBPD) resulted to be the best from a psychometric point of view.

CONCLUSIONS: Though the gold standard for diagnosis remains a detailed diagnostic interview, this review will encourage clinicians to use validated tools to accurately assess ICDs.}, } @article {pmid31162621, year = {2019}, author = {Limandri, BJ}, title = {Evidence-Based Prescribing in Mental Health Nursing.}, journal = {Journal of psychosocial nursing and mental health services}, volume = {57}, number = {6}, pages = {9-13}, doi = {10.3928/02793695-20190517-02}, pmid = {31162621}, issn = {0279-3695}, mesh = {Advanced Practice Nursing/methods ; Drug Prescriptions/*nursing ; *Evidence-Based Nursing ; Humans ; Mental Disorders/*drug therapy ; Neuropharmacology/education ; *Psychiatric Nursing ; }, abstract = {Since Sackett et al.'s epic throw down of the gauntlet in 1996, the hallmark of quality health care practice has been evidence-based clinical decision making. But what does it mean to base one's practice on evidence, and what are the barriers to evidence-based prescribing? The current article addresses these questions and offers suggestions to improve one's evidence-based practice. [Journal of Psychosocial Nursing and Mental Health Services, 57(6), 9-13.].}, } @article {pmid31161027, year = {2019}, author = {Becker, E and Christ, A}, title = {Rejection of Schmidt et al.'s estimators for bear population size.}, journal = {Ecology and evolution}, volume = {9}, number = {10}, pages = {6157-6164}, pmid = {31161027}, issn = {2045-7758}, abstract = {Aerial distance sampling of bears to estimate population size has been used throughout many parts of Alaska. The distance sampling models are complex since they need to account for undetected bears and differences in detection probabilities. This will require covariates and mark-recapture data. The models proposed by Schmidt et al. do not use covariates or mark-recapture data and are inappropriate for these surveys.}, } @article {pmid31159829, year = {2019}, author = {Biondo, PD and King, S and Minhas, B and Fassbender, K and Simon, JE and , }, title = {How to increase public participation in advance care planning: findings from a World Café to elicit community group perspectives.}, journal = {BMC public health}, volume = {19}, number = {1}, pages = {679}, pmid = {31159829}, issn = {1471-2458}, support = {201500790//Alberta Innovates - Health Solutions/ ; 201201157//Alberta Innovates - Health Solutions/ ; }, mesh = {*Advance Care Planning ; Alberta ; Awareness ; *Community Participation ; Female ; Health Services Needs and Demand ; Humans ; Male ; }, abstract = {BACKGROUND: In 2014, Alberta, Canada broke new ground in having the first provincial healthcare policy and procedure for advance care planning (ACP), the process of communicating and documenting a person's future healthcare preferences. However, to date public participation and awareness of ACP remains limited. The aim of this initiative was to elicit community group perspectives on how to help people learn about and participate in ACP.

METHODS: Targeted invitations were sent to over 300 community groups in Alberta (e.g. health/disease, seniors/retirement, social/service, legal, faith-based, funeral planning, financial, and others). Sixty-seven participants from 47 community groups attended a "World Café". Participants moved between tables at fixed time intervals, and in small groups discussed three separate ACP-related questions. Written comments were captured by participants and facilitators. Each comment was coded according to Michie et al.'s Theoretical Domains Framework, and mapped to the Capability, Opportunity and Motivation behavior change system (COM-B) in order to identify candidate intervention strategies.

RESULTS: Of 800 written comments, 76% mapped to the Opportunity: Physical COM-B component of behavior, reflecting a need for access to ACP resources. The most common intervention functions identified pertained to Education, Environmental Restructuring, Training, and Enablement. We synthesized the intervention functions and qualitative comments into eight recommendations for engaging people in ACP. These pertain to access to informational resources, group education and facilitation, health system processes, use of stories, marketing, integration into life events, inclusion of business partners, and harmonization of terminology.

CONCLUSIONS: There was broad support for the role of community groups in promoting ACP. Eight recommendations for engaging the public in ACP were generated and have been shared with stakeholders.}, } @article {pmid31154927, year = {2019}, author = {Munder, T and Flückiger, C and Leichsenring, F and Abbass, AA and Hilsenroth, MJ and Luyten, P and Rabung, S and Steinert, C and Wampold, BE}, title = {[Not Available].}, journal = {Zeitschrift fur Psychosomatische Medizin und Psychotherapie}, volume = {65}, number = {2}, pages = {178-182}, doi = {10.13109/zptm.2019.65.2.178}, pmid = {31154927}, issn = {1438-3608}, mesh = {*Depression ; *Depressive Disorder ; Emotions ; Humans ; Psychotherapy ; }, abstract = {Objective: Background regarding a recent debate between Cuijpers et al. (2019a, b) and the authors (Munder et al. 2019) about the efficacy of psychotherapy for depression is given. Method: A main reason for the discrepancy in Cuijpers et al.'s and our conclusions is discussed. Results: In our view the discrepancy is due, among other things, to a blurred distinction between questions of relative and absolute efficacy of psychotherapy. Although the efficacy of psychotherapy vis-à-vis alternative treatments may be ambiguous, there can be little doubt about the benefits of psychotherapy relative to no treatment. Conclusion: We do not think that raising fundamental concerns about the value of psychotherapy is a service to the field. We argue that moving the field forward requires a focus on how psychotherapy works and how the access to psychotherapy can be increased.}, } @article {pmid31131901, year = {2019}, author = {Ouyang, J and Chen, KT and Gong, E and Pauly, J and Zaharchuk, G}, title = {Ultra-low-dose PET reconstruction using generative adversarial network with feature matching and task-specific perceptual loss.}, journal = {Medical physics}, volume = {46}, number = {8}, pages = {3555-3564}, pmid = {31131901}, issn = {2473-4209}, support = {//Michael J. Fox Foundation/ ; //Foundation of the American Society of Neuroradiology/ ; //Core/ ; //GE Healthcare/ ; P41 EB015891/EB/NIBIB NIH HHS/United States ; P50 AG047366/AG/NIA NIH HHS/United States ; }, mesh = {Image Processing, Computer-Assisted/*methods ; *Machine Learning ; *Positron-Emission Tomography ; *Radiation Dosage ; Signal-To-Noise Ratio ; }, abstract = {PURPOSE: Our goal was to use a generative adversarial network (GAN) with feature matching and task-specific perceptual loss to synthesize standard-dose amyloid Positron emission tomography (PET) images of high quality and including accurate pathological features from ultra-low-dose PET images only.

METHODS: Forty PET datasets from 39 participants were acquired with a simultaneous PET/MRI scanner following injection of 330 ± 30 MBq of the amyloid radiotracer 18F-florbetaben. The raw list-mode PET data were reconstructed as the standard-dose ground truth and were randomly undersampled by a factor of 100 to reconstruct 1% low-dose PET scans. A 2D encoder-decoder network was implemented as the generator to synthesize a standard-dose image and a discriminator was used to evaluate them. The two networks contested with each other to achieve high-visual quality PET from the ultra-low-dose PET. Multi-slice inputs were used to reduce noise by providing the network with 2.5D information. Feature matching was applied to reduce hallucinated structures. Task-specific perceptual loss was designed to maintain the correct pathological features. The image quality was evaluated by peak signal-to-noise ratio (PSNR), structural similarity (SSIM), and root mean square error (RMSE) metrics with and without each of these modules. Two expert radiologists were asked to score image quality on a 5-point scale and identified the amyloid status (positive or negative).

RESULTS: With only low-dose PET as input, the proposed method significantly outperformed Chen et al.'s method (Chen et al. Radiology. 2018;290:649-656) (which shows the best performance in this task) with the same input (PET-only model) by 1.87 dB in PSNR, 2.04% in SSIM, and 24.75% in RMSE. It also achieved comparable results to Chen et al.'s method which used additional magnetic resonance imaging (MRI) inputs (PET-MR model). Experts' reading results showed that the proposed method could achieve better overall image quality and maintain better pathological features indicating amyloid status than both PET-only and PET-MR models proposed by Chen et al. CONCLUSION: Standard-dose amyloid PET images can be synthesized from ultra-low-dose images using GAN. Applying adversarial learning, feature matching, and task-specific perceptual loss are essential to ensure image quality and the preservation of pathological features.}, } @article {pmid31128572, year = {2019}, author = {Hostler, TJ and Poerio, GL and Blakey, E}, title = {Still More Than a Feeling: Commentary on Cash et al., "Expectancy Effects in the Autonomous Sensory Meridian Response" and Recommendations for Measurement in Future ASMR Research.}, journal = {Multisensory research}, volume = {32}, number = {6}, pages = {521-531}, doi = {10.1163/22134808-20191366}, pmid = {31128572}, issn = {2213-4808}, mesh = {Acoustic Stimulation ; Adaptation, Physiological/*physiology ; Attention/*physiology ; *Biomedical Research ; Emotions/*physiology ; Humans ; Photic Stimulation ; Sensation/*physiology ; Sensory Deprivation ; }, abstract = {Autonomous Sensory Meridian Response (ASMR) - the sensory phenomenon experienced by some people in response to visual and auditory stimuli such as whispering - has attracted substantial public attention but is not yet well understood or well established within the scientific community. Recent research published in PeerJ by Cash, Heisick and Papesh (2018) investigated whether ASMR could be a placebo effect (resulting from expectation) rather than a genuine experience triggered by ASMR-inducing stimuli. In this article, we provide a commentary on Cash et al.'s findings and argue that they provide evidence for (rather than against) the veracity of ASMR. We discuss issues regarding the measurement of ASMR and end by providing some recommendations on how to assess ASMR as both a state and a trait, in the hope of galvanising collaborative research efforts in the emerging field of ASMR.}, } @article {pmid31121895, year = {2019}, author = {Lee, J and Yu, S and Park, K and Park, Y and Park, Y}, title = {Secure Three-Factor Authentication Protocol for Multi-Gateway IoT Environments.}, journal = {Sensors (Basel, Switzerland)}, volume = {19}, number = {10}, pages = {}, pmid = {31121895}, issn = {1424-8220}, support = {2017R1A2B1002147//Ministry of Science ICT and Future Planning/ ; 21A20131600011//Ministry of Education/ ; }, abstract = {Internet of Things (IoT) environments such as smart homes, smart factories, and smart buildings have become a part of our lives. The services of IoT environments are provided through wireless networks to legal users. However, the wireless network is an open channel, which is insecure to attacks from adversaries such as replay attacks, impersonation attacks, and invasions of privacy. To provide secure IoT services to users, mutual authentication protocols have attracted much attention as consequential security issues, and numerous protocols have been studied. In 2017, Bae et al. presented a smartcard-based two-factor authentication protocol for multi-gateway IoT environments. However, we point out that Bae et al.'s protocol is vulnerable to user impersonation attacks, gateway spoofing attacks, and session key disclosure, and cannot provide a mutual authentication. In addition, we propose a three-factor mutual authentication protocol for multi-gateway IoT environments to resolve these security weaknesses. Then, we use Burrows-Abadi-Needham (BAN) logic to prove that the proposed protocol achieves secure mutual authentication, and we use the Automated Validation of Internet Security Protocols and Applications (AVISPA) tool to analyze a formal security verification. In conclusion, our proposed protocol is secure and applicable in multi-gateway IoT environments.}, } @article {pmid31120303, year = {2019}, author = {Rodondi, PY and Lüthi, E and Dubois, J and Roy, E and Burnand, B and Grass, G}, title = {Complementary Medicine Provision in an Academic Hospital: Evaluation and Structuring Project.}, journal = {Journal of alternative and complementary medicine (New York, N.Y.)}, volume = {25}, number = {6}, pages = {606-612}, doi = {10.1089/acm.2019.0062}, pmid = {31120303}, issn = {1557-7708}, mesh = {*Academic Medical Centers ; *Complementary Therapies ; *Delivery of Health Care ; Focus Groups ; Health Personnel ; *Health Services ; *Hospitals ; Humans ; Surveys and Questionnaires ; Switzerland ; }, abstract = {Objectives: Complementary medicine (CM) has become increasingly available in hospital settings in several countries. Nonetheless, there are disparities in the provision and organization of CM between hospitals and even within a single hospital. This was the case at Lausanne University Hospital, where neither a registry of CM practices nor homogeneous guidelines for the provision of CM existed. The board of directors mandated the use of an internal consultant to assess practices, delineate the ward's needs, and draft proposals to structure the provision of CM services. Design: Lescarbeau et al.'s integrated model of consultation was used. Settings/Location: Academic medical center, Switzerland. Subjects: Heads of departments, medical and nurse directors, and CM practitioners. Interventions: Semi-structured interviews, online survey, and focus groups were used to focus on CM availability, needs, and practices; CM practitioner background, training, and position in the hospital; and the type of patients treated. Results: The assessment identified 15 types of CM in 51 wards, provided by CM practitioners who represented the profiles of 8 types of health care professionals. Three barriers to implementing CM were identified: heterogeneity in CM practitioners' training and project implementation, lack of CM information for patients and health care professionals, and variable access to CM among hospital wards and resulting lack in continuity of care. Three main needs regarding CM were delineated: to ensure CM quality, to provide structured interdepartmental CM clinical services, and to provide CM information to patients and health care professionals. Three action priorities were selected by the board of directors: to develop structured CM clinical services; to select CM provision based on the specific criteria of scientific evidence, therapies already available at hospital, and specific ward's needs; and to provide CM information to patients and health care professionals. Conclusions: This assessment permitted to structure CM provision according to internal consultation.}, } @article {pmid31120164, year = {2019}, author = {Kanazawa, S}, title = {An association between women's physical attractiveness and the length of their reproductive career in a prospectively longitudinal nationally representative sample.}, journal = {American journal of human biology : the official journal of the Human Biology Council}, volume = {31}, number = {4}, pages = {e23256}, doi = {10.1002/ajhb.23256}, pmid = {31120164}, issn = {1520-6300}, mesh = {*Beauty ; England ; Female ; Humans ; Longitudinal Studies ; *Menarche ; *Menopause ; Middle Aged ; Prospective Studies ; *Reproduction ; Scotland ; Wales ; }, abstract = {OBJECTIVES: Why is physical attractiveness more important for women's mate value in long-term mating than in short-term mating? This article replicates Bovet et al.'s (Journal of Evolutionary Biology. 2018; 31:229-238) recent finding that physically attractive women have a later expected age of menopause.

METHODS: I analyzed the prospectively longitudinal, nationally representative sample of women in the National Child Development Study, applying t-test and multiple regression analyses.

RESULTS: Analyses showed that girls rated physically attractive at age 7 underwent menarche 3.12 months earlier than other girls, and they had 32% smaller odds of having undergone menopause before age 51. The results suggest that more physically attractive women have longer reproductive careers, explaining why physical attractiveness may be a more important determinant of women's mate value in long-term mating than in short-term mating.

CONCLUSIONS: Women's physical attractiveness predicts the timing of menarche and menopause, thereby the length of their reproductive careers.}, } @article {pmid31113425, year = {2019}, author = {Chesham, RA and Booth, JN and Sweeney, EL and Ryde, GC and Gorely, T and Brooks, NE and Moran, CN}, title = {Response to Daly-Smith et al.'s commentary on 'The Daily Mile makes primary school children more active, less sedentary and improves their fitness and body composition: a quasi-experimental pilot study'.}, journal = {BMC medicine}, volume = {17}, number = {1}, pages = {97}, pmid = {31113425}, issn = {1741-7015}, mesh = {Body Composition ; Child ; *Exercise ; Humans ; Physical Fitness ; Pilot Projects ; *Schools ; }, abstract = {We thank Daly-Smith et al. for taking the time to read the results of our pilot research study, describing it as an important and welcome contribution. Nonetheless, the authors argue six points against our conclusion. We contend that we addressed three of these points in our original discussion and disagree with their remaining points. Overall, their Commentary adds little to the topic of research into the Daily Mile™ that we had not already raised in our discussion. Additionally, they attribute statements to us that we did not make and ignore the raising of key issues in our original article. Given this, we stand by our original peer-reviewed conclusion that introducing the Daily Mile™ to the primary school day appears to be an effective intervention for increasing levels of moderate to vigorous physical activity, reducing sedentary time, increasing physical fitness and improving body composition, and that these findings have relevance for teachers, policy-makers, public health practitioners and health researchers.}, } @article {pmid31112073, year = {2019}, author = {Goldberg, NN and Huang, X and Majidi, C and Novelia, A and O'Reilly, OM and Paley, DA and Scott, WL}, title = {On Planar Discrete Elastic Rod Models for the Locomotion of Soft Robots.}, journal = {Soft robotics}, volume = {6}, number = {5}, pages = {595-610}, doi = {10.1089/soro.2018.0104}, pmid = {31112073}, issn = {2169-5180}, abstract = {Modeling soft robots that move on surfaces is challenging from a variety of perspectives. A recent formulation by Bergou et al. of a rod theory that exploits new developments in discrete differential geometry offers an attractive, numerically efficient avenue to help overcome some of these challenges. Their formulation is an example of a discrete elastic rod theory. In this article, we consider a planar version of Bergou et al.'s theory and, with the help of recent works on Lagrange's equations of motion for constrained systems of particles, show how it can be used to model soft robots that are composed of segments of soft material folded and bonded together. We then use our formulation to examine the dynamics of a caterpillar-inspired soft robot that is actuated using shape memory alloys and exploits stick-slip friction to achieve locomotion. After developing and implementing procedures to prescribe the parameters for components of the soft robot, we compare our calibrated model to the experimental behavior of the caterpillar-inspired soft robot.}, } @article {pmid31109350, year = {2019}, author = {Mohammad, HR and Debrock, W and Mellon, SJ and Cooke, P}, title = {Response to review article published titled 'Total ankle arthroplasty versus ankle arthrodesis - a comparison of outcomes over the last decade'.}, journal = {Journal of orthopaedic surgery and research}, volume = {14}, number = {1}, pages = {142}, pmid = {31109350}, issn = {1749-799X}, mesh = {Ankle Joint/*surgery ; Arthrodesis/methods/*trends ; Arthroplasty, Replacement, Ankle/adverse effects/*trends ; Humans ; *Review Literature as Topic ; Time Factors ; Treatment Outcome ; }, abstract = {We write in response to Lawton et al.'s (J Orthop Surg Res 12:76, 2017) important systematic review comparing the outcomes of total ankle replacement (TAR) and ankle arthrodesis (AA) after reviewing the existing literature. Traditionally, AA was the gold standard treatment for ankle osteoarthritis but there is renewed interest in TAR given modern design advantages of preserved ankle motion and gait. We outline some pertinent issues for surgeons to consider when interpreting results from review articles comparing treatment types given the limitations of primary studies. These include significant clinical heterogeneity from the indication for surgery, different treatment type subgroups and from poorly defined clinical outcomes.}, } @article {pmid31107442, year = {2019}, author = {Garone, MG and de Turris, V and Soloperto, A and Brighi, C and De Santis, R and Pagani, F and Di Angelantonio, S and Rosa, A}, title = {Conversion of Human Induced Pluripotent Stem Cells (iPSCs) into Functional Spinal and Cranial Motor Neurons Using PiggyBac Vectors.}, journal = {Journal of visualized experiments : JoVE}, volume = {}, number = {147}, pages = {}, doi = {10.3791/59321}, pmid = {31107442}, issn = {1940-087X}, mesh = {*Cell Differentiation/drug effects ; Doxycycline/pharmacology ; Gene Expression Regulation/drug effects ; Genes, Homeobox ; Genetic Vectors/*metabolism ; Humans ; Induced Pluripotent Stem Cells/*cytology ; Motor Neurons/*cytology ; Plasmids/metabolism ; Skull/*cytology ; Spinal Cord/*cytology ; }, abstract = {We describe here a method to obtain functional spinal and cranial motor neurons from human induced pluripotent stem cells (iPSCs). Direct conversion into motor neuron is obtained by ectopic expression of alternative modules of transcription factors, namely Ngn2, Isl1 and Lhx3 (NIL) or Ngn2, Isl1 and Phox2a (NIP). NIL and NIP specify, respectively, spinal and cranial motor neuron identity. Our protocol starts with the generation of modified iPSC lines in which NIL or NIP are stably integrated in the genome via a piggyBac transposon vector. Expression of the transgenes is then induced by doxycycline and leads, in 5 days, to the conversion of iPSCs into MN progenitors. Subsequent maturation, for 7 days, leads to homogeneous populations of spinal or cranial MNs. Our method holds several advantages over previous protocols: it is extremely rapid and simplified; it does not require viral infection or further MN isolation; it allows generating different MN subpopulations (spinal and cranial) with a remarkable degree of maturation, as demonstrated by the ability to fire trains of action potentials. Moreover, a large number of motor neurons can be obtained without purification from mixed populations. iPSC-derived spinal and cranial motor neurons can be used for in vitro modeling of Amyotrophic Lateral Sclerosis and other neurodegenerative diseases of the motor neuron. Homogeneous motor neuron populations might represent an important resource for cell type specific drug screenings.}, } @article {pmid31106616, year = {2021}, author = {Buus, AAØ and Hejlsen, OK and Dorisdatter Bjørnes, C and Laugesen, B}, title = {Experiences of pre- and postoperative information among patients undergoing knee arthroplasty: a systematic review and narrative synthesis.}, journal = {Disability and rehabilitation}, volume = {43}, number = {2}, pages = {150-162}, doi = {10.1080/09638288.2019.1615997}, pmid = {31106616}, issn = {1464-5165}, mesh = {*Arthroplasty, Replacement, Knee ; Health Personnel ; Humans ; Narration ; Patient Discharge ; Postoperative Period ; Qualitative Research ; }, abstract = {Purpose: The aim of this review was to identify and synthesize knowledge of how patients undergoing knee arthroplasty experience pre- and postoperative information provided by healthcare professionals.Materials and methods: A systematic review and narrative synthesis was conducted in accordance with Popay et al.'s guidelines which involve 1) developing a preliminary synthesis; 2) exploring relationships; and 3) assessing the robustness of the synthesis. Qualitative and quantitative studies were considered for inclusion, and a systematic, extensive search was conducted in scientific databases.Results: A total of 31 studies were included in this review. The analysis resulted in five synthesized themes: 1) Support in the decision to undergo surgery; 2) Confidence versus uncertainty in the preparation for surgery; 3) Prerequisites for feeling secure before discharge; 4) Struggling through rehabilitation at home; and 5) Unmet expectations and endeavoring to accept realities.Conclusions: The findings illustrate the complexities of patients' experiences of information from healthcare professionals and its significance for how they manage challenges throughout the surgical care pathway. Information from healthcare professionals influences patients' knowledge, skills and confidence in the journey through knee arthroplasty. Therefore, it is important that healthcare professionals recognize patients' support requirements and adapt information to their individual needs.Implications for rehabilitationHealthcare professionals should encourage more dialog with patients and adapt information to their individual circumstances and needs throughout the surgical care pathway.It is important that healthcare professionals provide ongoing information and repeat information throughout the entire surgical care pathway in order to facilitate predictability and improve patients' ability to comprehend and assimilate information.Improved access to information and advice from healthcare professionals following knee arthroplasty will offer patients reassurance and increase their confidence in managing postoperatively at home.Patients who require enhanced information and guidance from healthcare professionals need to be identified in order to support their progress and achieve the best possible postoperative outcomes.}, } @article {pmid31070441, year = {2019}, author = {Presseau, C and Litz, BT and Kline, NK and Elsayed, NM and Maurer, D and Kelly, K and Dondanville, KA and Mintz, J and Young-McCaughan, S and Peterson, AL and Williamson, DE}, title = {An epidemiological evaluation of trauma types in a cohort of deployed service members.}, journal = {Psychological trauma : theory, research, practice and policy}, volume = {11}, number = {8}, pages = {877-885}, doi = {10.1037/tra0000465}, pmid = {31070441}, issn = {1942-969X}, support = {//U.S. Department of Defense/ ; }, mesh = {Adult ; Combat Disorders/*epidemiology ; Female ; Humans ; Male ; Military Personnel/*statistics & numerical data ; Psychological Trauma/classification/*epidemiology ; Stress Disorders, Post-Traumatic/*epidemiology ; United States/epidemiology ; Young Adult ; }, abstract = {OBJECTIVE: Using Stein et al.'s (2012) categorization scheme for typing Criterion A events (i.e., Life Threat to Self, Life Threat to Other, Aftermath of Violence, Traumatic Loss, Moral Injury by Self, and Moral Injury by Other) and extending Litz et al.'s (2018) prior work, we investigated the prevalence of trauma types, prevalence of posttraumatic stress disorder within each trauma type, and associations between trauma types and behavioral and mental health outcomes for an epidemiological sample of service members.

METHOD: Criterion A events coded by independent raters (kappas = .85-1.00) were used to determine prevalence rates and to conduct two path models examining all trauma types in relation to mental health outcomes.

RESULTS: Consistent with prior research, we found events containing Life Threat to Self (51.1%) and Life Threat to Other (30.8%) to be most prevalent, and a majority of events (62.9%) were coded with one trauma type. Although least prevalent, Aftermath of Violence (12.0%) and Moral Injury by Self (4.8%) were most frequently and strongly associated with worse mental health outcomes. Path models predicted a very small amount of variance in continuous outcomes, thus limiting the interpretation of findings.

CONCLUSION: More epidemiological research is needed to understand the role of trauma type in relation to mental health among nontreatment-seeking service members. (PsycINFO Database Record (c) 2019 APA, all rights reserved).}, } @article {pmid31068175, year = {2019}, author = {Hietapakka, L and Elovainio, M and Wesolowska, K and Aalto, AM and Kaihlanen, AM and Sinervo, T and Heponiemi, T}, title = {Testing the psychometric properties of the Finnish version of the cross-cultural competence instrument of healthcare professionals (CCCHP).}, journal = {BMC health services research}, volume = {19}, number = {1}, pages = {294}, pmid = {31068175}, issn = {1472-6963}, support = {303607//Strategic Research Council/ ; }, mesh = {Adult ; Clinical Competence/*statistics & numerical data ; *Cultural Competency/education ; Cultural Diversity ; Female ; Finland ; Health Services Research ; Humans ; Job Satisfaction ; Male ; Nurses, International/psychology/*statistics & numerical data ; Psychometrics/instrumentation ; Reproducibility of Results ; Surveys and Questionnaires ; *Transcultural Nursing ; }, abstract = {BACKGROUND: To test the validity of the Finnish version of the Bernhard et al.'s Cross-Cultural Competence instrument of Healthcare Professionals (CCCHP).

METHODS: The study sample comprised registered nurses (N = 810) from the Finnish "Competent workforce for the future" -project (COPE). Exploratory factor analyses and structural equation modelling were applied to test structural validity of the CCCHP. Internal consistency of the sub-scales was evaluated using the Cronbach's alphas. Criterion validity was explored in terms of received education for multicultural work, perceived difficulty of patients, and job satisfaction variables.

RESULTS: The revised version of the instrument including four (motivation/curiosity, attitudes, skills and emotions/empathy) of the five original dimensions provided satisfactory psychometric properties (internal consistency, a good model fit of the data). Of the four remaining competence sub-scales, motivation/curiosity, attitudes and emotions/empathy were associated with the amount of received education for multicultural work, and all with perceived difficulty of patients, and all but attitudes with job satisfaction.

CONCLUSION: This revised Finnish version of the CCCHP provides a useful tool for studies focusing on the healthcare personnel's cross-cultural competence in delivering effective and culturally sensitive healthcare services for patients from different cultures.}, } @article {pmid31058799, year = {2019}, author = {Salam, A and Atkins, ER and Hsu, B and Webster, R and Patel, A and Rodgers, A}, title = {Efficacy and safety of triple versus dual combination blood pressure-lowering drug therapy: a systematic review and meta-analysis of randomized controlled trials.}, journal = {Journal of hypertension}, volume = {37}, number = {8}, pages = {1567-1573}, doi = {10.1097/HJH.0000000000002089}, pmid = {31058799}, issn = {1473-5598}, mesh = {*Antihypertensive Agents/administration & dosage/adverse effects/pharmacology/therapeutic use ; Blood Pressure/*drug effects ; Double-Blind Method ; Drug Therapy, Combination ; Humans ; Hypertension/*drug therapy ; Randomized Controlled Trials as Topic ; }, abstract = {BACKGROUND AND OBJECTIVES: Most patients with hypertension need at least two drugs to achieve goal blood pressure. This systematic review assessed efficacy and safety of triple versus dual combination therapy for the management of hypertension.

METHODS: Publication databases, clinical trial registries and regulatory agency websites were searched until April 2018 for double-blind randomized controlled trials (RCTs) comparing triple with dual therapy of BP-lowering drugs, for at least 3 weeks, among patients with hypertension. Meta-analyses for efficacy and safety outcomes were performed using random-effects model. Regimen efficacy was predicted using the Therapeutic Intensity Score (TIS) and the Law et al. method (which predict dose doubling increases efficacy by 100% and around 20%, respectively), and compared with observed efficacy.

RESULTS: Fourteen RCTs (11 457 participants) were included. Overall, triple compared with dual therapy reduced BP by 5.4/3.2 mmHg (P < 0.001), and improved BP control by 58 versus 45% [relative risk (RR) 1.33 (95% CI 1.25-1.41)], whereas incidence of withdrawals because of adverse events were 3.3 versus 3.4% [RR 1.24 (95% CI 1.00-1.54), P = 0.05]. Law et al.'s method was superior to TIS in predicting differences in efficacy between triple and dual therapies. For patients uncontrolled on submaximal dose dual therapy, adding a third drug achieved on average approximately four times more BP reduction than doubling the dose of dual therapy component drugs (6.0/3.6 versus 1.5/0.8 mmHg, respectively).

CONCLUSION: Addition of a third drug is likely to be more efficacious without increasing adverse events, compared with increasing dose of existing dual therapy. Early use of triple therapy can significantly improve hypertension control.}, } @article {pmid31057078, year = {2020}, author = {Friedlander, ML and Angus, LE and Xu, M and Wright, ST and Stark, NM}, title = {A close look at therapist contributions to narrative-emotion shifting in a case illustration of brief dynamic therapy.}, journal = {Psychotherapy research : journal of the Society for Psychotherapy Research}, volume = {30}, number = {3}, pages = {402-416}, doi = {10.1080/10503307.2019.1609710}, pmid = {31057078}, issn = {1468-4381}, mesh = {Adult ; Female ; Humans ; *Professional-Patient Relations ; *Psychotherapeutic Processes ; *Psychotherapy, Brief ; *Psychotherapy, Psychodynamic ; }, abstract = {Objective: In a secondary analysis of Friedlander et al.'s [(2018). "If those tears could talk, what would they say?" multi-method analysis of a corrective experience in brief dynamic therapy. Psychotherapy Research, 28, 217-234. doi:10.1080/10503307.2016.1184350] case study of Hanna Levenson's Brief Dynamic Therapy over Time (from APA's Psychotherapy in Six Sessions DVD series), we re-visited the Narrative-Emotion Process Coding (Angus, L. E., Boritz, T., Bryntwick, E., Carpenter, N., Macaulay, C., & Khattra, J. (2017). The Narrative-Emotion Process Coding System 2.0: A multi-methodological approach to identifying and assessing narrative-emotion process markers in psychotherapy. Psychotherapy Research, 27, 253-269. doi:10.1080/10503307.2016.1238525) to identify specific therapist behaviors that may have facilitated the client's movement from expressing mostly Problem markers in early sessions to expressing considerably more Transition and Change markers in later sessions. Method: Using open coding and constant comparison qualitative methods, we identified Levenson's behaviors immediately preceding the client's "change shifts" (Problem → Transition/Change and Transition → Change) and "problem shifts" (Transition/Change → Problem). Results: Compared to problem shifts, change shifts were preceded by more therapist behavior reflecting Attaching New Meaning (e.g., linking the client's self-deprecation to her avoidant behavior) and Exploring/Expanding emotions (e.g., inviting the client to give voice to her tears), cognitions (e.g., pointing out the client's self-talk) and motivation (e.g., reflecting on the client's dissatisfaction with her defenses). Conclusions: In this successful case, facilitative therapist behavior reflected common therapeutic responses (e.g., validating the client's perspective) as well as responses characteristic of brief dynamic therapy (e.g., interpreting the client's defenses) and the therapist's personal style (e.g., repeating the client's words for emphasis).}, } @article {pmid31052789, year = {2019}, author = {Chen, H and Long, S and Tang, X and Wu, X and Wang, W and Qin, Y}, title = {Modeling of scaling of a diode longitudinally pumped metastable rare gas with a master oscillator power amplifier.}, journal = {Optics express}, volume = {27}, number = {9}, pages = {12504-12516}, doi = {10.1364/OE.27.012504}, pmid = {31052789}, issn = {1094-4087}, abstract = {There has been recent interest in diode pumped metastable rare gas lasers (DPRGLs) and their scaling to higher powers, due to the advantages of excellent beam quality and high quantum efficiency. In this paper, a cw diode pumped rare gas amplifier (DPRGA) with single-pass longitudinally pumped configuration is studied theoretically based on master oscillator and power amplifier (MOPA). A five-level kinetic model of DPRGAs is first established. Then, the influences of gain medium density, pump and seed laser intensities and gain length on DPRGA performance are simulated and analyzed. The results of numerical simulation agree well with those of Rawlins et al.'s experiment. With the best set of working parameters, the amplification factor reaches 22.18 dB, at pump intensity of 50 kW/cm[2] and seed laser intensity of 100 W/cm[2]. Parameter optimization is helpful for design of a relatively high-power DPRGL system.}, } @article {pmid31050916, year = {2019}, author = {Vuletich, HA and Payne, BK}, title = {Stability and Change in Implicit Bias.}, journal = {Psychological science}, volume = {30}, number = {6}, pages = {854-862}, doi = {10.1177/0956797619844270}, pmid = {31050916}, issn = {1467-9280}, mesh = {Humans ; Longitudinal Studies ; *Prejudice ; *Social Environment ; *Universities ; }, abstract = {Can implicit bias be changed? In a recent longitudinal study, Lai and colleagues (2016, Study 2) compared nine interventions intended to reduce racial bias across 18 university campuses. Although all interventions changed participants' bias on an immediate test, none were effective after a delay. This study has been interpreted as strong evidence that implicit biases are difficult to change. We revisited Lai et al.'s study to test whether the stability observed reflected persistent individual attitudes or stable environments. Our reanalysis (N = 4,842) indicates that individual biases did not return to preexisting levels. Instead, campus means returned to preexisting campus means, whereas individual scores fluctuated mostly randomly. Campus means were predicted by markers of structural inequality. Our results are consistent with the theory that implicit bias reflects biases in the environment rather than individual dispositions. This conclusion is nearly the opposite of the original interpretation: Although social environments are stable, individual implicit biases are ephemeral.}, } @article {pmid31047990, year = {2019}, author = {Karnik, NS and Winiarski, DA}, title = {Editorial: Bullying and Suicide Risk: Restructuring Prevention, Identification, and Treatment to Address a Global Mental Health Crisis.}, journal = {Journal of the American Academy of Child and Adolescent Psychiatry}, volume = {58}, number = {9}, pages = {851-852}, doi = {10.1016/j.jaac.2019.04.007}, pmid = {31047990}, issn = {1527-5418}, support = {TL1 TR002388/TR/NCATS NIH HHS/United States ; }, mesh = {Adolescent ; *Bullying ; Child ; *Crime Victims ; Global Health ; Humans ; Mental Health ; Suicide, Attempted ; }, abstract = {Bullying is a global phenomenon with significant mental health consequences. Although bullying prevention programs have garnered attention over the last several years, the results of these programs have been mixed, at best. As Koyanagi et al.[1] highlight in this issue of the Journal, the consequences of bullying can be dire, particularly when they occur during a critical developmental period. Using the Global School-based Student Health Survey, this article reports on a sample of more than 130,000 youths aged 12 to 15 years sampled in a structured manner across 48 countries with a range of geographic representation and some socioeconomic diversity. The results of this study find that across 47 of 48 countries, children and adolescents have an average 3-fold greater risk of suicide attempt when faced with bullying. In addition, there was a dose-dependent impact of the number of days bullied to odds of suicide attempt. In recent years, rates of suicide have been steadily increasing around the globe, with suicide being the second leading cause of death among 15- to-29-year-olds in 2016.[2] Koyanagi et al.'s timely article not only illustrates that suicide is a growing global health problem but also emphasizes the need to re-evaluate our existing strategies using a multisystemic approach to screening, prevention, and treating bullied youths.}, } @article {pmid31046563, year = {2019}, author = {McDonald, JL and Oetting, JB}, title = {Nonword Repetition Across Two Dialects of English: Effects of Specific Language Impairment and Nonmainstream Form Density.}, journal = {Journal of speech, language, and hearing research : JSLHR}, volume = {62}, number = {5}, pages = {1381-1391}, pmid = {31046563}, issn = {1558-9102}, support = {R01 DC009811/DC/NIDCD NIH HHS/United States ; }, mesh = {Black or African American ; Aged ; Female ; Humans ; *Language ; Male ; Middle Aged ; Southeastern United States ; Southwestern United States ; Specific Language Disorder/*diagnosis ; *Speech ; United States ; }, abstract = {Purpose Nonword repetition (NWR) has been proposed as a culturally and linguistically fair measure of children's language abilities that is useful for the identification of specific language impairment (SLI). However, Moyle, Heilmann, and Finneran (2014) suggested that the density of a child's nonmainstream forms also influences NWR in ways that could complicate its use. Using speakers of either African American English (AAE) or Southern White English (SWE), we asked if NWR performance differed in children with SLI and same dialect-speaking typically developing (TD) children and if nonmainstream form density impacted their scores. Method The participants were 106 kindergartners (AAE: SLI n = 35; TD n = 35; SWE: SLI n = 18; TD n = 18; groups matched for age and IQ) who performed the NWR task of Dollaghan and Campbell (1998) . Nonmainstream form density measures were gathered from listener judgments of conversational samples. Results NWR performance differed between those with and without SLI, but the difference was smaller in AAE than in SWE, especially at the longest syllable length. Nonmainstream form density was found to further explain NWR performance beyond the children's SLI status for AAE speakers; density and SLI status were confounded for the SWE speakers, making it harder to disentangle the effects of each in that dialect. Conclusions Results indicate the NWR may differ in diagnostic utility between speakers of different dialects. Results also support Moyle et al.'s (2014) finding that density affects NWR. Thus, NWR is more sensitive to dialectal differences than originally assumed.}, } @article {pmid31043236, year = {2019}, author = {Mueller, AS}, title = {Why Thirteen Reasons Why may elicit suicidal ideation in some viewers, but help others.}, journal = {Social science & medicine (1982)}, volume = {232}, number = {}, pages = {499-501}, doi = {10.1016/j.socscimed.2019.04.014}, pmid = {31043236}, issn = {1873-5347}, mesh = {Adolescent ; Humans ; Popular Culture ; *Suicidal Ideation ; Suicide/*psychology ; Television/*standards/trends ; }, abstract = {When the popular Netflix series 13 Reasons Why (13RW) debuted, scholars were quick to raise concerns that the show may encourage suicide as an option, particularly for vulnerable audience members; nonetheless, others pushed back, noting that the evidence used to draw a link between exposure to media and actual suicide risk suffers from methodological weaknesses and that censoring mental health topics may do more harm than good. The problem highlighted by the debate is that researchers generally lack the kinds of studies that would truly help us understand if a show like 13RW is problematic, and if it is, which specific storylines carry risk. Indeed, this general lack of the empirical evidence is precisely why the study by Arendt and his colleagues (2019) in this issue makes such an important contribution to the literature. With this commentary, I (1) review what we know and what we don't about the media, 13RW, and suicide, (2) discuss Arendt et al.'s unique insights, and (3) outline an agenda for future research that will allow us to better answer how, when, and for whom exposure to media stories like 13RW harms - or helps - youth.}, } @article {pmid31035690, year = {2019}, author = {Shin, S and Kwon, T}, title = {A Lightweight Three-Factor Authentication and Key Agreement Scheme in Wireless Sensor Networks for Smart Homes.}, journal = {Sensors (Basel, Switzerland)}, volume = {19}, number = {9}, pages = {}, pmid = {31035690}, issn = {1424-8220}, support = {UD170109ED//Defense Acquisition Program Administration(DAPA) and Agency for Defense Development(ADD)/ ; }, abstract = {A wireless sensor network (WSN) is used for a smart home system's backbone that monitors home environment and controls smart home devices to manage lighting, heating, security and surveillance. However, despite its convenience and potential benefits, there are concerns about various security threats that may infringe on privacy and threaten our home life. For protecting WSNs for smart homes from those threats, authentication and key agreement are basic security requirements. There have been a large number of proposed authentication and key agreement scheme for WSNs. In 2017, Jung et al. proposed an efficient and security enhanced anonymous authentication with key agreement scheme by employing biometrics information as the third authentication factor. They claimed that their scheme resists on various security attacks and satisfies basic security requirements. However, we have discovered that Jung et al.'s scheme possesses some security weaknesses. Their scheme cannot guarantee security of the secret key of gateway node and security of session key and protection against user tracking attack, information leakage attack, and user impersonation attack. In this paper, we describe how those security weaknesses occur and propose a lightweight three-factor authentication and key agreement scheme in WSNs for smart homes, as an improved version of Jung et al.'s scheme. We then present a detailed analysis of the security and performance of the proposed scheme and compare the analysis results with other related schemes.}, } @article {pmid31035245, year = {2019}, author = {Ripley, AJ and Clapp, JD and Wilkowski, BM}, title = {PTSD and anger: Evaluation of an indirect effect model in a civilian trauma sample.}, journal = {Journal of behavior therapy and experimental psychiatry}, volume = {64}, number = {}, pages = {149-157}, doi = {10.1016/j.jbtep.2019.02.004}, pmid = {31035245}, issn = {1873-7943}, support = {P20 GM103432/GM/NIGMS NIH HHS/United States ; }, mesh = {Adult ; Anger/*physiology ; Female ; *Hostility ; Humans ; Male ; Models, Biological ; Psychological Trauma/*physiopathology ; Severity of Illness Index ; Stress Disorders, Post-Traumatic/*physiopathology ; Thinking/*physiology ; Young Adult ; }, abstract = {BACKGROUND AND OBJECTIVES: Theoretical models propose that PTSD symptoms and subjective anger are indirectly associated through hostile attribution bias, physiological reactivity, and aggressive psycho-motor scripts (Chemtob, Novaco, Hamada, Gross, & Smith, 1997). Originally developed to account for symptoms observed in military personnel, proposed anger mechanisms have received limited attention in civilian populations. The current study looked to evaluate the generalizability of Chemtob et al.'s model in trauma-exposed university students (N = 152).

METHODS: Trauma exposure and corresponding symptoms were assessed during an initial screening procedure. Hostile attributions and aggressive scripts were examined prior to a laboratory-based anger induction procedure. Physiological reactivity was monitored throughout the provocation task. Ratings of subjective anger and anger recovery were completed following the induction period. Relations of post-trauma symptoms with subjective anger through hypothesized anger processes were examined using bootstrapped estimates of indirect effects.

RESULTS: A significant indirect effect of PTSD severity on state-level anger was noted for hostile attribution bias (ab = 0.020, 95% CI [0.002, 0.041]) and a marginal effect through aggressive inclinations (ab = 0.015, 95% CI [-0.001, 0.039]). Data failed to provide evidence for physiological reactivity as an intervening variable. Trauma symptoms did not moderate anger recovery following the provocation task.

LIMITATIONS: Induction of anger in a sub-clinical sample may limit tests of hypothesized effects and the generalizability of the present findings.

CONCLUSIONS: Results indicate the proposed model may be applicable beyond combat trauma samples and suggest potential anger-related targets for PTSD treatment.}, } @article {pmid31031874, year = {2019}, author = {Trinh, KV and Diep, D and Chen, KJQ}, title = {Systematic Review of Episodic Migraine Prophylaxis: Efficacy of Conventional Treatments Used in Comparisons with Acupuncture.}, journal = {Medical acupuncture}, volume = {31}, number = {2}, pages = {85-97}, pmid = {31031874}, issn = {1933-6586}, abstract = {Objective: A Cochrane Systematic Review published by Linde et al. in 2016 found moderate evidence suggesting that acupuncture is "at least non-inferior" to conventional prophylactic drug treatments (flunarizine, metoprolol, and valproic acid) for episodic migraine prophylaxis. The evidence for the efficacy of these conventional treatments must be verified to strengthen and validate the original comparison made in Linde et al.'s 2016 review. The aim of the current authors' systematic review was to verify the efficacy of the conventional treatments used in Linde et al.'s 2016 comparison with acupuncture. Materials and Methods: Search strategies were applied to find studies that could verify the efficacy of conventional treatments for treating episodic migraines. Relevant outcomes and dosages were extracted from the retrieved studies. Each study's quality was assessed, using the Cochrane's collaboration tool for assessing risk of bias and the Cochrane GRADE [Grading of Recommendations Assessment, Development, and Evaluation] scale. Results: There is high-quality evidence suggesting that prophylactic drug treatment, at the treatment dosage ranges used in Linde et al.'s 2016 review, reduced headache frequency at a 3-month follow-up, compared to placebo. Headache frequency at a 6-month follow-up, and responses (at least 50% reduction of headache frequency) at 3-month and 6-month follow-ups could not be assessed. Conclusions: These findings strengthened Linde et al.'s 2016 comparison of conventional treatments and acupuncture for reducing headache frequency at a 3-month follow-up. For episodic migraine prophylaxis, moderate evidence suggests that acupuncture is "at least non-inferior," to now-proven, conventional treatments. This raises significant questions in the debate concerning claims that acupuncture is a placebo-based treatment and the prescriptions of proven conventional treatments that have similar effects as acupuncture.}, } @article {pmid31026290, year = {2019}, author = {Meisner, J and Mooney, SJ and Rabinowitz, PM}, title = {The curse of dimensionality: Animal-related risk factors for pediatric diarrhea in western Kenya, and methods for dealing with a large number of predictors.}, journal = {PloS one}, volume = {14}, number = {4}, pages = {e0215982}, pmid = {31026290}, issn = {1932-6203}, support = {T32 ES015459/ES/NIEHS NIH HHS/United States ; }, mesh = {Animals ; Case-Control Studies ; Child ; Computer Simulation ; Confounding Factors, Epidemiologic ; Diarrhea/*epidemiology ; Humans ; Kenya/epidemiology ; Latent Class Analysis ; Models, Biological ; Regression Analysis ; Risk Factors ; }, abstract = {BACKGROUND: Pediatric diarrhea, a leading cause of under-five mortality, is predominantly infectious in etiology. As many putative causal agents are zoonotic, animal exposure is a likely risk factor. To evaluate the effect of animal-related factors on moderate to severe childhood diarrhea in rural Kenya, where animal contact is common, Conan et al. studied 73 matched case-control pairs from 2009-2011, collecting rich exposure data on many dimensions of animal contact. We review the challenges associated with analyzing moderately-sized datasets with a large number of predictors and present two alternative methodological approaches.

We conducted a simulation study to demonstrate that forward stepwise selection results in overfit models when data are high-dimensional, and that p values reported directly from the data used to train these models are misleading. We described how automated methods of variable selection, attractive when the number of predictors is large, can result in overadjustment bias. We proposed an alternative a priori regression approach not subject to this bias. Applied to Conan et al.'s data, this approach found a non-significant but positive trend for household's sharing of water sources with livestock or poultry, child's presence for poultry slaughter, and child's habit of playing where poultry sleep or defecate. For many predictors evaluated few pairs were discordant, suggesting matching compromised the power of this analysis. Finally, we proposed latent variable modeling as a complimentary approach and performed Item Response Theory modeling on Conan et al.'s data, with animal contact as the latent trait. We found a moderate but non-significant effect (OR 1.21, 95% CI 0.78, 1.87, unit = 1 standard deviation).

CONCLUSIONS/SIGNIFICANCE: Automated methods of model selection are appropriate for prediction models when fit and evaluated on separate samples. However when the goal is inference, these methods can produce misleading results. Furthermore, case-control matching should be done with caution.}, } @article {pmid31015364, year = {2019}, author = {Sergi, C}, title = {EPAS 1, congenital heart disease, and high altitude: disclosures by genetics, bioinformatics, and experimental embryology.}, journal = {Bioscience reports}, volume = {39}, number = {5}, pages = {}, pmid = {31015364}, issn = {1573-4935}, mesh = {*Altitude ; Animals ; Basic Helix-Loop-Helix Transcription Factors/genetics ; Computational Biology ; Disclosure ; *Heart Diseases ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics ; Mutation ; Tibet ; Vascular Endothelial Growth Factor A/genetics ; }, abstract = {The high-altitude environment is a challenge for human settlement. Low oxygen concentrations, extreme cold, and a harsh arid climate are doubtlessly challenges for the colonization of the Tibetan plateau. I am delighted to comment on the article of Pan et al. (2018) on mutations in endothelial PAS domain-containing protein 1 (EPAS1) in congenital heart disease in Tibetans. In humans, the EPAS1 gene is responsible for coding EPAS1 protein, an alias of which is HIF2α, an acronym for hypoxia-inducible factor 2 alpha. EPAS1 is a type of hypoxia-inducible factors, which are collected as a group of transcription factors involved in body response to oxygen level. EPAS1 gene is active under hypoxic conditions and plays an essential role in the development of the heart and in the management of the catecholamine balance, mutations of which have been identified in neuroendocrine tumors. In this article, Pan et al. investigated Tibetan patients with and without non-syndromic congenital heart disease. They identified two novel EPAS1 gene mutations, of which N203H mutation significantly affected the transcription activity of the vascular endothelial growth factor (VEGF) promoter, particularly in situations of hypoxia. VEGF is a downstream target of HIF-2 (other than HIF-1), and the expression levels of either HIF-1α or HIF-2α correlate positively to VEGF expression. Pan et al.'s data may be of incitement to further evaluate protein-protein interaction and using experimental animal models. Moreover, it may also be a stimulus for setting up genetic epidemiologic studies for other populations living at high altitudes.}, } @article {pmid30986890, year = {2019}, author = {Wagstaff, A}, title = {Measuring catastrophic medical expenditures: Reflections on three issues.}, journal = {Health economics}, volume = {28}, number = {6}, pages = {765-781}, doi = {10.1002/hec.3881}, pmid = {30986890}, issn = {1099-1050}, mesh = {Algorithms ; Catastrophic Illness/*economics ; Family Characteristics ; Financing, Personal ; *Health Expenditures ; Humans ; Income ; Insurance, Health ; Surveys and Questionnaires ; }, abstract = {In the "basic" approach, medical expenses are catastrophic if they exceed a prespecified percentage of consumption or income; the approach tells us if expenses cause a large percentage reduction in living standards. The ability-to-pay (ATP) approach defines expenses as catastrophic if they exceed a prespecified percentage of consumption less expenses on nonmedical necessities or an allowance for them. The paper argues that the ATP approach does not tell us whether expenses are large enough to undermine a household's ability to purchase nonmedical necessities. The paper compares the income-based and consumption-based variants of the basic approach, and shows that if the individual is a borrower after a health shock, the income-based ratio will exceed the consumption-based ratio, and both will exceed the more theoretically correct Flores et al. ratio; whereas if the individual continues to be a saver after a health shock, the ordering is reversed and the income-based ratio may not overestimate Flores et al.'s ratio. Last, the paper proposes a lifetime money metric utility (LMMU) approach defining medical expenses as catastrophic in terms of their lifetime consequences. Under certain assumptions, the LMMU and Flores et al. approaches are identical, and neither requires data on how households finance their medical expenses.}, } @article {pmid30973267, year = {2019}, author = {Shanks, DR and Vadillo, MA}, title = {Still no evidence that risk-taking and consumer choices can be primed by mating motives: Reply to Sundie, Beal, Neuberg, and Kenrick (2019).}, journal = {Journal of experimental psychology. General}, volume = {148}, number = {4}, pages = {e12-e22}, doi = {10.1037/xge0000597}, pmid = {30973267}, issn = {1939-2222}, support = {//United Kingdom Economic and Social Research Council/International ; //Economic and Social Research Council/International ; //Comunidad de Madrid; Programa de Atracción de Talento Investigador/International ; //Agencia Estatal de Investigación, Ministerio de Economía y Competitividad/International ; }, mesh = {Humans ; *Motivation ; *Motor Activity ; Publication Bias ; Risk-Taking ; }, abstract = {Shanks et al. (2015) challenged the evidence that various forms of decision making can be influenced by romantic/mating primes. In their comment, Sundie, Beal, Neuberg, and Kenrick (2019) question both the meta-analysis and the 8 studies Shanks et al. reported, and describe an alternative p-curve analysis that they interpret as showing that romantic priming is a genuine phenomenon. In this reply, we comment on several contradictions in Sundie et al.'s article. First, they suggest that Shanks et al.'s replication experiments yielded different results from the original studies because we failed to appreciate the contextual sensitivity of romantic priming effects, but this argument rests largely on evidence from the very studies we were unable to replicate, and a wealth of other evidence suggests that social priming effects are largely invariant across samples and settings. Second, Sundie et al. criticize the selection rule by which Shanks et al. identified relevant priming studies, but then go on to include exactly the same set of studies in their p-curve analysis. Third, they criticize Shanks et al.'s selection of statistical results from these studies and propose a much wider selection, but then acknowledge that their selection process is poorly suited to assessing publication bias and p-hacking. Fourth, we show that their p-curve analysis, far from demonstrating that this literature is unaffected by p-hacking, in fact shows the exact opposite. Sundie et al. claim that Shanks et al.'s priming manipulation was demonstrably weak, but their argument is based on a confusion between different dependent measures. We conclude that romantic priming remains unproven, and urge researchers in this field to undertake high-powered preregistered replication studies. (PsycINFO Database Record (c) 2019 APA, all rights reserved).}, } @article {pmid30973020, year = {2021}, author = {Mercado, A and Venta, A and Henderson, C and Pimentel, N}, title = {Trauma and cultural values in the health of recently immigrated families.}, journal = {Journal of health psychology}, volume = {26}, number = {5}, pages = {728-740}, doi = {10.1177/1359105319842935}, pmid = {30973020}, issn = {1461-7277}, mesh = {Adult ; Child ; *Emigrants and Immigrants ; *Hispanic or Latino ; Humans ; Parents ; United States ; }, abstract = {This study examined Ruiz et al.'s sociocultural model of Hispanic health resilience by assessing trauma exposure and symptoms and Hispanic cultural values in relation to the physical health of 97 Central American immigrant families, within 24 hours of arrival to the United States. Increased posttraumatic stress symptoms, but not exposure, were associated with increased physical health concerns for parents and children. Hispanic cultural values moderated trauma-health relations for adult health only. Identifying posttraumatic stress symptoms as a significant correlate of physical health in Latino immigrant parents and children is critical to identifying vulnerabilities in need of future research and interventions.}, } @article {pmid30949639, year = {2019}, author = {González-Gallardo, S and Jancik, V and Díaz-Gómez, DG and Cortés-Guzmán, F and Hernández-Balderas, U and Moya-Cabrera, M}, title = {Reactivity patterns for the activation of CO2 and CS2 with alumoxane and aluminum hydrides.}, journal = {Dalton transactions (Cambridge, England : 2003)}, volume = {48}, number = {17}, pages = {5595-5603}, doi = {10.1039/c9dt00515c}, pmid = {30949639}, issn = {1477-9234}, abstract = {Carbon dioxide is readily fixed when reacting with either alumoxane dihydride [{MeLAl(H)} 2(μ-O)] (1) or aluminum dihydride [MeLAlH2] (2) (MeL = HC[(CMe)N(2,4,6-Me3C6H2)]2-) to produce bimetallic aluminum formates [(MeLAl)2(μ-OCHO)2(μ-O)] (3) and [(MeLAl)2(μ-OCHO)2(μ-H)2] (5), respectively. Furthermore, [(MeLAl)2(μ-OCHO)2(μ-OH)2] (4) is easily obtained upon the reaction of 3 or 5 with H2O. The stability of the unusual dialuminum diformate dihydride core observed in 5 stems from the proximity of the Al centers allowing the formation of two Al-HAl bridges and precluding further hydride transfer to the HCO2 moieties. Contrary to this behavior, 1 and 2 react with CS2 giving cyclic alumoxane and aluminum sulfides [(MeLAl)2(μ-S)(μ-O)] (6) and [{MeLAl(μ-S)} 2] (7), respectively. The molecular structures of 3-7 were characterized by IR, Raman, solution or solid-state (MAS) NMR spectroscopy and mass spectrometry and for 4-7 were characterized by X-ray diffraction studies. NMR kinetic studies and DFT calculations suggest that the mechanisms for the formation of 6 and 7 involve the transfer of a hydride group forming transient aluminum thioformate intermediates which proceed to form Al-S-Al moieties through the cleavage of C-S bonds and insertion of a sulfur atom, followed by the elimination of thioformaldehyde.}, } @article {pmid30948243, year = {2019}, author = {Coughlin, DG and Petrovitch, H and White, LR and Noorigian, J and Masaki, KH and Ross, GW and Duda, JE}, title = {Most cases with Lewy pathology in a population-based cohort adhere to the Braak progression pattern but 'failure to fit' is highly dependent on staging system applied.}, journal = {Parkinsonism & related disorders}, volume = {64}, number = {}, pages = {124-131}, pmid = {30948243}, issn = {1873-5126}, support = {R01 AG017155/AG/NIA NIH HHS/United States ; R01 NS041265/NS/NINDS NIH HHS/United States ; TL1 TR001880/TR/NCATS NIH HHS/United States ; U01 AG019349/AG/NIA NIH HHS/United States ; }, mesh = {Aged ; Aged, 80 and over ; Autopsy ; Cohort Studies ; Disease Progression ; Female ; Humans ; Lewy Bodies/pathology ; Lewy Body Disease/*classification/*pathology ; Male ; Parkinson Disease/*classification/*pathology ; }, abstract = {Braak et al.'s 2003 paper detailing the caudo-rostral progression of Lewy body pathology (LP) formed the foundation of current understanding of disease spread in Parkinson's disease (PD); however, its methods are difficult to recreate and consequently multiple new staging systems emerged to recapitulate Braak's staging system using standard neuropathological methods and to account for other patterns of LP. Studies using these systems have documented widely variable rates of cases that 'fail to fit' expected patterns of LP spread. This could be due to population differences, features of individual systems, or may constitute under-recognized patterns of disease. We examined 324 neuropathological cases from the Honolulu Asia Aging Study and applied four different LP staging systems to determine the proportion of cases adhering to different staging methodologies and those that 'fail to fit' expected patterns of LP. Of 141 cases with LP (24: PD, 8: Dementia with Lewy bodies (DLB), 109: Incidental Lewy body disease (ILBD)), our application of Braak et al., 2003 classified 83.7%, Müller et al., 2005 classified 87.9%, Beach et al., 2009 classified 100%, and Leverenz et al., 2008 classified 98.6%. There were significant differences in the cases classifiable by the Leverenz and Beach systems versus the Braak and Müller systems (p < 0.001 for each). In this population-based autopsy cohort with a high prevalence of ILBD, the majority of cases were consistent with the progression characterized by the Braak et al. however, the determination of cases as atypical is highly dependent on the staging system applied.}, } @article {pmid30947958, year = {2019}, author = {Kacem, H and Diagne, PM and Miquel, J}, title = {Ultrastructural organisation of the spermatozoon of Allopodocotyle tunisiensis Derbel and Neifar, 2009 (Digenea, Opecoelidae), an intestinal parasite of Solea aegyptiaca Chabanaud, 1927 (Teleostei, Soleidae).}, journal = {Tissue & cell}, volume = {57}, number = {}, pages = {1-7}, doi = {10.1016/j.tice.2019.01.008}, pmid = {30947958}, issn = {1532-3072}, mesh = {Animals ; Flatfishes/parasitology ; Male ; Spermatozoa/*ultrastructure ; Trematoda/*ultrastructure ; }, abstract = {The ultrastructure of the spermatozoon of Allopodocotyle tunisiensis (Digenea, Opecoelidae), an intestinal parasite of Solea aegyptiaca (Teleostei, Soleidae), is described by transmission electron microscopy (TEM). The mature spermatozoon is a filiform cell that exhibits two axonemes of different length with the 9+'1' pattern of trepaxonematan Platyhelminthes. In the anterior spermatozoon extremity, cortical microtubules are absent. They appear after the disappearance of an anterior electron-dense material, being initially in a continuous and submembranous layer. They surround only partially the sperm cell. Later, these cortical microtubules are distributed into two bundles. Additionally, the spermatozoon of A. tunisiensis shows two mitochondria, a nucleus, an external ornamentation of the plasma membrane, spine-like bodies, and a large amount of glycogen granules. According to the location of the external ornamentation, A. tunisiensis presents a Quilichini et al.'s type 2 spermatozoon. With respect to the posterior extremity, the sperm cell of A. tunisiensis corresponds to the Quilichini et al.'s opecoelid type. The morphology of the first mitochondrion with a U-shaped posterior extremity is described for the first time in a digenean spermatozoon.}, } @article {pmid30945011, year = {2019}, author = {Renuka, K and Kumari, S and Li, X}, title = {Design of a Secure Three-Factor Authentication Scheme for Smart Healthcare.}, journal = {Journal of medical systems}, volume = {43}, number = {5}, pages = {133}, pmid = {30945011}, issn = {1573-689X}, support = {2018JJ3191//Natural Science Foundation of Hunan Province (CN)/ ; }, mesh = {Communication ; Computer Security/*standards ; Computer Systems/*standards ; Confidentiality ; Electronic Health Records/standards ; Health Information Exchange/*standards ; Humans ; }, abstract = {Now-a-days, the society is witnessing a keen urge to enhance the quality of healthcare services with the intervention of technology in the health sector. The main focus in transforming traditional healthcare to smart healthcare is on facilitating the patients as well as medical professionals. However, this changover is not easy due to various issues of security and integrity associated with it. Security of patients's personal health record and privacy can be handled well by permitting only authorized access to the confidential health-data via suitably designed authentication scheme. In pursuit to contribute in this direction, we came across the role of Universal Serial Bus (USB), the most widely accepted interface, in enabling communication between peripheral devices and a host controller like laptop, personal computer, smart phone, tablet etc. In the process, we analysed a recently proposed a three-factor authentication scheme for consumer USB Mass Storage Devices (MSD) by He et al. In this paper, we demonstrate that He et al.'s scheme is vulnerable to leakage of temporary but session specific information attacks, late detection of message replay, forward secrecy attacks, and backward secrecy attacks. Then motivated with the benefits of USB, we propose a secure three-factor authentication scheme for smart healthcare.}, } @article {pmid30940275, year = {2019}, author = {Perlovsky, L}, title = {Reductionism - simplified and scientific.}, journal = {The Behavioral and brain sciences}, volume = {42}, number = {}, pages = {e21}, doi = {10.1017/S0140525X18001127}, pmid = {30940275}, issn = {1469-1825}, mesh = {Brain ; *Brain Diseases ; Humans ; *Psychopathology ; Research ; }, abstract = {In this commentary on Borsboom et al.'s target article, I address an inadequate, simplified use of the idea of "reductionism" in clinical psychology and psychiatry. This is important because reductionism is a fundamental methodology of science. Explaining mental states and processes in terms of biological and brain states and processes is fundamental for the science of psychology. I also briefly address a fundamental methodology of the goal of psychology as a hard science.}, } @article {pmid30940232, year = {2019}, author = {Field, M and Heather, N and Wiers, RW}, title = {Indeed, not really a brain disorder: Implications for reductionist accounts of addiction.}, journal = {The Behavioral and brain sciences}, volume = {42}, number = {}, pages = {e9}, doi = {10.1017/S0140525X18001024}, pmid = {30940232}, issn = {1469-1825}, mesh = {*Behavior, Addictive ; Brain ; *Brain Diseases ; Humans ; Psychopathology ; Research ; }, abstract = {Borsboom et al.'s formulation provides an opportunity for a fundamental rethink about the "brain disease model" of addiction that dominates research, treatment, policy, and lay understanding of addiction. We also demonstrate how the American opioid crisis provides a contemporary example of how "brain disease" is not moderated by the environmental context but is instead crucially dependent upon it.}, } @article {pmid30940223, year = {2019}, author = {Desseilles, M and Phillips, C}, title = {Beyond reduction with the representation: The need for causality with full complexity to unravel mental health.}, journal = {The Behavioral and brain sciences}, volume = {42}, number = {}, pages = {e6}, doi = {10.1017/S0140525X18001267}, pmid = {30940223}, issn = {1469-1825}, mesh = {*Brain Diseases ; Humans ; *Mental Disorders ; Mental Health ; Psychopathology ; Research ; }, abstract = {In this commentary on Borsboom et al.'s target article, we argue that researchers should be aware of the historical development of models in neuroscience. Considering the importance of causality in anatomo-clinical approach and stressing the complexity of mental phenomenon, we provide new insight on reductionism and representation limitation.}, } @article {pmid30924236, year = {2019}, author = {Gill, SD and Fuscaldo, G and Page, RS}, title = {Patient-centred care through a broader lens: Supporting patient autonomy alongside moral deliberation.}, journal = {Emergency medicine Australasia : EMA}, volume = {31}, number = {4}, pages = {680-682}, doi = {10.1111/1742-6723.13287}, pmid = {30924236}, issn = {1742-6723}, mesh = {*Decision Making, Shared ; Humans ; Morals ; Patient-Centered Care/*ethics/methods ; *Personal Autonomy ; Physician-Patient Relations/ethics ; }, abstract = {Patient-centred care (PCC) is an essential component of high-quality healthcare and shared decision-making is its cornerstone. Yet, integrating the principles of PCC into healthcare practice is not always straightforward and shared decision-making can be complicated and ethically demanding. While ethicists and academics routinely debate moral aspects of clinical care, such discussion among clinicians is less overt. In this paper, we use Emmanuel et al.'s deliberative model to provide a practical framework for considering ethical aspects of PCC and shared decision-making. The model encourages us to appreciate PCC through a broader lens and consider patient autonomy alongside other moral obligations such as justice and the equitable distribution of finite resources. The model can be used by healthcare providers, patients and caregivers to facilitate dialogue and moral deliberation regarding the merit of their preferences and values; in this way, individualised care can be delivered without compromising other important ethical obligations.}, } @article {pmid30913737, year = {2019}, author = {Gong, J and Li, Z and Zhang, R and Li, J and Shi, X}, title = {Synergistic Effects of Nano-Montmorillonite and Polyethylene Microfiber in Foamed Paste with High Volume Fly Ash Binder.}, journal = {Journal of nanoscience and nanotechnology}, volume = {19}, number = {8}, pages = {4465-4473}, doi = {10.1166/jnn.2019.16353}, pmid = {30913737}, issn = {1533-4880}, abstract = {Foamed cement-based materials have attracted much attention as a new type of thermal insulation materials (TIMs) that may offer a sustainable solution to the built environments. This laboratory study explores the combined use of nano-montmorillonite and polyethylene microfiber in foamed paste with high volume fly ash (HVFA) binder. A total of 16 foamed HVFA paste mixtures were fabricated which consisted of 70% Class F fly ash, 30% Portland cement, 2% sodium alpha-olefin sulfonate, 0.38% Na3PO4, and 2% nano-montmorillonite. The dosage and type of polyethylene microfibers (90 μm in diameter) were explored in the present study, with six dosages (0, 0.1%, 0.2%, 0.3%, 0.4%, 0.5% by volume) and three lengths (3 mm, 6 mm, and 9 mm) tested. Based on the experimental results, the highest 28-day rupture strength (1.51 MPa) was achieved with the use of 3-mm long PE microfibers at 0.4 vol.%. Synergistic utilization of nMMT and microfibers exhibited a great influence on the dry density and water absorption of the foamed paste. The SEM micrographs illustrated the multiple mechanisms by which the microfibers serve to reduce shrinkage-induced cracking of the foamed paste. Energy-dispersive X-ray spectroscopy was employed to obtain the contents of Ca, Si, Al, S and mole ratios of Ca/Si, Ca/(Si + Al), S/Ca, and Al/Si in the hardened pastes, which reveal the difference in hydration products near or away from the nMMT-pretreated polyethylene microfibers. The results of microhardness test were also used to elucidate such nano-/micro-synergistic effects, which improved the bonding between microfibers and foamed paste matrix. A mechanism was proposed to explain the role of various admixtures and the balanced performance of such inorganic TIMs.}, } @article {pmid30903924, year = {2019}, author = {McNair, FD and Havens, J and Surko, M and Weinberger, E and Baetz, C and Moaveni, M and Bart, A and Marr, M and Quinlan, C and Horwitz, SM}, title = {Post-traumatic stress and related symptoms among juvenile detention residents: Results from intake screening.}, journal = {Child abuse & neglect}, volume = {92}, number = {}, pages = {22-31}, doi = {10.1016/j.chiabu.2019.03.011}, pmid = {30903924}, issn = {1873-7757}, mesh = {Adolescent ; Bullying/psychology ; Crime Victims/psychology ; Depressive Disorder/etiology ; Female ; Humans ; Male ; Mass Screening ; Prisoners/*psychology ; Prisons ; Retrospective Studies ; Self-Injurious Behavior/psychology ; Sex Offenses/psychology ; Stress Disorders, Post-Traumatic/*psychology ; Substance-Related Disorders/psychology ; }, abstract = {BACKGROUND: Juvenile justice-involved youth have high rates of trauma exposure, physical and sexual abuse and PTSD. Several factors have been found to be related to PTSD symptoms in youth including number and chronicity of traumatic events.

OBJECTIVE: To simultaneously examine the relationships between allostatic load (defined here as number of traumatic experiences), poly-victimization (exposure to two or more forms of victimization based on 5 of the 6 categories in Ford et al.'s 2010 study), physical/sexual abuse and PTSD in justice-involved youth.

PARTICIPANTS AND SETTING: The sample consisted of 1984 youth in juvenile detention in a Northeastern city. The sample was 73.4% male and the majority of youth were either African American or Hispanic.

METHODS: Clinicians collected demographic and psychosocial information, and measured symptoms of PTSD, depression, and problematic substance use.

RESULTS: Results showed that youth with more traumas, those who experienced poly-victimization and those who experienced physical/sexual assault/abuse were not only more likely to have PTSD, but also more likely to have depression, thoughts of suicide/self-harm, and problematic substance use (as indicated by the presence of 2 or more of 6 possible indicators). Poly-victimization was a stronger correlate of PTSD than number of traumas or physical/sexual assault/abuse. However, among youth with PTSD, number of traumas was associated with co-occurring problems while poly-victimization and physical/sexual assault/abuse were not.

CONCLUSIONS: Findings can be used to help direct resources to juvenile justice-involved youth who are most in need of treatment.}, } @article {pmid30901293, year = {2019}, author = {Meier, ME}, title = {Is There a Positive Association Between Working Memory Capacity and Mind Wandering in a Low-Demand Breathing Task? A Preregistered Replication of a Study by Levinson, Smallwood, and Davidson (2012).}, journal = {Psychological science}, volume = {30}, number = {5}, pages = {789-797}, doi = {10.1177/0956797619837942}, pmid = {30901293}, issn = {1467-9280}, mesh = {Adolescent ; Adult ; Awareness/*physiology ; Cognition/*physiology ; Female ; Humans ; Individuality ; Male ; Memory, Short-Term/*physiology ; Predictive Value of Tests ; Respiration ; Wandering Behavior/*psychology ; Young Adult ; }, abstract = {Levinson, Smallwood, and Davidson (2012, Experiment 2) found that working memory capacity (WMC) correlated positively with mind-wandering rates measured by thought probes in a breath-awareness task but was unassociated with the tendency to self-catch mind wandering. Here, I sought to replicate the associations between mind wandering and WMC in Levinson et al.'s breath-awareness task. The data from the current study, collected from 315 subjects (ns differed among analyses) and two measures of WMC, suggest that if WMC correlates with probe-caught mind wandering, the association is most likely negative. In addition, the evidence regarding self-caught mind wandering is consistent with that found by Levinson et al. for the sum of self-caught responses, but when self-caught responses were considered in proportion to probe-caught mind wandering, modest evidence was found for a positive association with WMC.}, } @article {pmid30893354, year = {2019}, author = {Pak, K and Pak, S and Ho, C and Pak, M and Hwang, C}, title = {Anonymity preserving and round effective three-party authentication key exchange protocol based on chaotic maps.}, journal = {PloS one}, volume = {14}, number = {3}, pages = {e0213976}, pmid = {30893354}, issn = {1932-6203}, mesh = {Algorithms ; Communication ; Computer Security/*instrumentation ; Confidentiality ; Health Information Exchange ; Humans ; Information Systems/*instrumentation ; Telemedicine/*instrumentation ; Trust ; }, abstract = {Three-party authentication key exchange (3PAKE) is a protocol that allows two users to set up a common session key with the help of a trusted remote server, which is effective for secret communication between clients in a large-scale network environment. Since chaotic maps have superior characteristics, researchers have recently presented some of the studies that apply it to authentication key exchange and cryptography. Providing user anonymity in the authentication key exchange is one of the important security requirements to protect users' personal secrets. We analyse Lu et al.'s scheme which attempts to provide user anonymity and we prove that his scheme has errors in the key exchange phase and password change phase. We propose a round-effective three-party authentication key exchange (3PAKE) protocol that provides user anonymity and we analyse its security properties based on BAN logic and AVISPA tool.}, } @article {pmid30883524, year = {2019}, author = {Farhangi, M and Feuer, W and Galor, A and Bouhassira, D and Levitt, RC and Sarantopoulos, CD and Felix, ER}, title = {Modification of the Neuropathic Pain Symptom Inventory for use in eye pain (NPSI-Eye).}, journal = {Pain}, volume = {160}, number = {7}, pages = {1541-1550}, pmid = {30883524}, issn = {1872-6623}, support = {R01 EY026174/EY/NEI NIH HHS/United States ; P30 EY014801/EY/NEI NIH HHS/United States ; I01 BX004893/BX/BLRD VA/United States ; R21 NS105880/NS/NINDS NIH HHS/United States ; I01 CX001089/CX/CSRD VA/United States ; R01 DE022903/DE/NIDCR NIH HHS/United States ; L30 EY019842/EY/NEI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Anesthetics/pharmacology ; Dry Eye Syndromes/complications/diagnosis ; Eye Pain/*diagnosis/etiology ; Factor Analysis, Statistical ; Female ; Humans ; Male ; Mental Health ; Middle Aged ; Neuralgia/*diagnosis ; Pain Measurement/*methods/standards ; Psychometrics ; Reproducibility of Results ; Surveys and Questionnaires ; }, abstract = {Chronic eye pain, which has previously been assumed to be due to ocular surface abnormalities (ie, "dry eye [DE] disease"), has recently garnered attention as a potential indicator of neuropathic ocular pain in some patients. The purpose of this study was to evaluate the psychometric properties of a modified version of the Neuropathic Pain Symptom Inventory in individuals with eye pain (NPSI-Eye). Enrolled participants (n = 397) completed the NPSI-Eye, general pain severity questionnaires, DE symptom report, and psychological health indices. Participants also underwent mechanical pain sensitivity testing of the cornea, tear film assessment, and evaluation of the efficacy of anesthetic eye drops to relieve pain. Short-term test-retest reliability of the NPSI-Eye was excellent (intraclass correlation coefficient = 0.98, P < 0.001). Correlations between the NPSI-Eye and indicators of general eye pain were ≥0.65 (P < 0.001), whereas correlations between the NPSI-Eye and DE symptom severity and psychological health indices were lower (rho = 0.56, 0.32, 0.37; all P < 0.001). Individuals who reported little or no decrease in pain after anesthetic eye drops (hypothesized to indicate eye pain with at least partial central involvement) had significantly higher NPSI-Eye scores than participants whose eye pain was completely relieved by anesthetic (P < 0.05). Overall, our results support preliminary validation of the NPSI-Eye, yielding similar metrics to those reported in Bouhassira et al.'s original NPSI publication (2004). However, additional evaluation and refinement of some questions may be desirable, including the potential elimination of items that were not highly endorsed.}, } @article {pmid30880410, year = {2019}, author = {Gulati, R and Pauley, D}, title = {The Half Embrace of Psychic Bisexuality.}, journal = {Journal of the American Psychoanalytic Association}, volume = {67}, number = {1}, pages = {97-121}, doi = {10.1177/0003065119827043}, pmid = {30880410}, issn = {1941-2460}, mesh = {Bisexuality/*psychology ; Gender Identity ; Humans ; *Psychoanalytic Theory ; Sexual Behavior/*psychology ; }, abstract = {The discourse on psychic bisexuality is explored as it unfolds in Freud's writings, in contemporary papers by LGBTQ psychoanalysts, and in a volume of essays, Psychic Bisexuality, published in 2018 by a group of prominent French and British analysts (Perelberg 2018). The greater acceptance of nonnormative sexualities and genders is reshaping the discourse on bisexuality and gender in many corners of our profession, yet, as the Perelberg volume attests, that evolution is far from universal. A strain of unquestioned heteronormativity and cisgenderism is evident in Perelberg et al.'s description of the fundamentals of psychic life, a strain that has roots (via a certain one-sided reading of Lacan) in Freud's unresolved mourning of his inchoate homosexual self. A more embracing vision of bisexuality would seek to "hold," rather than enact, the grief and anxiety associated with the development of myriad diverse personal patterns.}, } @article {pmid30869975, year = {2020}, author = {Reis, DJ and Namekata, MS and Oehlert, ME and King, N}, title = {A preliminary review of the Beck Depression Inventory-II (BDI-II) in veterans: Are new norms and cut scores needed?.}, journal = {Psychological services}, volume = {17}, number = {3}, pages = {363-371}, doi = {10.1037/ser0000342}, pmid = {30869975}, issn = {1939-148X}, support = {//Veterans Affairs Eastern Kansas Healthcare System/ ; }, mesh = {Adult ; Age Factors ; Aged ; Ambulatory Care ; Depression/*diagnosis ; Depressive Disorder/*diagnosis ; Female ; Humans ; Male ; Mental Health Services ; Middle Aged ; Psychiatric Status Rating Scales/*standards/statistics & numerical data ; Psychometrics/*standards/statistics & numerical data ; Reproducibility of Results ; United States ; United States Department of Veterans Affairs ; *Veterans/statistics & numerical data ; }, abstract = {The Beck Depression Inventory-II (BDI-II) is used within the Veterans Health Administration (VHA) to measure depression symptom severity. This naturalistic study aimed to examine VHA-specific BDI-II use and establish normative data and psychometric properties. Initial BDI-II data for 152,260 individual veterans were extracted from preexisting medical records using the VA Informatics and Computing Infrastructure. BDI-II scores were compared against Beck, Steer, and Brown (1996)'s original sample, as well as across veteran subgroups. Exploratory and confirmatory factor analyses were also conducted. Similar to Beck et al.'s (1996) sample, the BDI-II was most frequently administered in outpatient psychiatric VHA settings, although it was also used in inpatient and medical settings. Veterans scored significantly higher on the BDI-II than the original comparison groups. This was true across diagnostic categories. The largest discrepancy was seen between nondepressed veterans and corresponding patients from the original sample (Cohen's d = 1.34). Older veterans endorsed less severe levels of depression symptomatology. Additionally, a 2-factor model similar to Beck et al.'s (1996) original solution provided the best fit to the data. Veterans reported higher levels of somatic-affective symptoms than cognitive symptoms. Although potentially useful, the BDI-II requires further investigation in veterans. Standard cut scores are not recommended for use in this population when evaluating severity of depression. A cut score of 27 or higher best differentiated between veterans with and without mood disorders in the current sample. Treatment providers should also consider using BDI-II factor scores, rather than the total score, to measure depressive symptom change. (PsycInfo Database Record (c) 2020 APA, all rights reserved).}, } @article {pmid30852917, year = {2019}, author = {Brandenburg, S and Oehl, M and Hartwig, C}, title = {Driving anger expression in Germany-Validation of the Driving Anger Expression Inventory for German drivers.}, journal = {Traffic injury prevention}, volume = {20}, number = {1}, pages = {52-57}, doi = {10.1080/15389588.2018.1493467}, pmid = {30852917}, issn = {1538-957X}, mesh = {Adult ; Aggression/*psychology ; *Anger ; Automobile Driving/*psychology/statistics & numerical data ; Factor Analysis, Statistical ; Female ; Germany ; Humans ; Male ; Middle Aged ; Psychometrics ; Reproducibility of Results ; Surveys and Questionnaires ; }, abstract = {OBJECTIVE: The main objective of this article is to examine whether the Driving Anger Expression Inventory (DAX) applies to German drivers because this scale has previously been given to drivers in many different countries.

METHODS: We applied German versions of the DAX, the Driving Anger Scale (DAS), and the State-Trait Anger Expression Inventory (STAXI) to a sample of 501 German drivers. We computed confirmatory factor analysis and principal axis factoring (PAF) analysis to examine the structure of driving anger expression in Germany. Finally, we related the drivers' anger exp ression scores to their driving anger experiences and their general anger propensities to assess the validity of the DAX for German drivers.

RESULTS: Results indicated that the DAX's original factor structure does not apply to German drivers because the confirmatory factor analysis did not show a good model fit. An item analysis revealed that many DAX items had no meaningful variability. They were excluded from further analysis. The subsequent PAF analysis indicated that German drivers do not use personal physical aggression to express their driving anger. Instead, they reported unique preventive anger expression management behavior. In addition, their driving anger expressions were significantly related to their driving anger experiences and their general anger propensities indicated the validity of the refined DAX for German drivers.

CONCLUSIONS: We conclude that German drivers do not use strong behaviors to express their driving anger. Many statements of Deffenbacher et al.'s (Behav Res Ther. 40:717-737, 2002) original American questionnaire were not applicable for our sample of German drivers. These findings are in line with several other studies showing discrepancies in driving anger expression in various countries. Future investigations should examine the reasons for discrepancies in driving anger expression.}, } @article {pmid30847292, year = {2019}, author = {Yilmaz, O and Candirli, C and Balaban, E and Demirkol, M}, title = {Evaluation of success criteria for temporomandibular joint arthrocentesis.}, journal = {Journal of the Korean Association of Oral and Maxillofacial Surgeons}, volume = {45}, number = {1}, pages = {15-20}, pmid = {30847292}, issn = {2234-7550}, abstract = {OBJECTIVES: The aim of this study was to use four sets of success criteria to evaluate the outcomes of arthrocentesis treatment with hyaluronic acid injection in patients with internal derangement (ID) of the temporomandibular joint (TMJ).

MATERIALS AND METHODS: The study included 40 patients diagnosed with unilateral Wilkes stage III TMJ dysfunction. Clinical parameters, including maximum mouth opening (MMO) and pain during function, were evaluated preoperatively, 6 months, and 1 year after TMJ arthrocentesis. Outcomes were assessed and compared using four sets of success criteria from the following: the American Association of Oral and Maxillofacial Surgeons (AAOMS; MMO ≥35 mm and visual analogue scale [VAS] score ≤3), Murakami et al.'s criteria (MMO >38 mm and VAS score <2), Emshoff and Rudisch criteria (MMO ≥35 mm and >50% pain reduction), and patient self-reports (self-evaluation of treatment as successful or unsuccessful).

RESULTS: Significant improvements in MMO and pain reduction during function were observed between the preoperative period and 6 months and 1 year postoperatively (P<0.01). The success rates of treatment determined using AAOMS (52.5%), Emshoff and Rudisch criteria (57.5%), and self-reported patient criteria (40.0%) were similar. Application of the Murakami et al. criteria reported the lowest success rate (12.5%).

CONCLUSION: The AAOMS and Emshoff and Rudisch criteria are consistent with patient expectations and can be used to assess treatment efficacy.}, } @article {pmid30845205, year = {2019}, author = {Osborne, T and Mulcahy, NJ}, title = {Reassessing shelter dogs' use of human communicative cues in the standard object-choice task.}, journal = {PloS one}, volume = {14}, number = {3}, pages = {e0213166}, pmid = {30845205}, issn = {1932-6203}, mesh = {Animals ; Association Learning ; Choice Behavior/*physiology ; Communication ; *Cues ; Dogs ; Female ; Humans ; Male ; Recognition, Psychology ; Reward ; }, abstract = {Unlike other animal species, domesticated pet dogs reliably use a range of human communicative cues to find a hidden reward in the object-choice task. One explanation for this finding is that dogs evolved skills for understanding human communicative behaviour during and as a result of human domestication. However, contrary to this domestication hypothesis, Udell et al. found domesticated shelter dogs failed to locate a hidden reward using a human's distal point cue, a cue pet dogs easily use. Hare et al., however, suggested the unorthodox methods used in Udell et al.'s object-choice task resulted in the shelter dogs failing to use human cues. In support of this, Hare et al. found that shelter dogs could use a human communicative pointing cue when tested with a standard object-choice task method. Yet in contrast to Udell et al., Hare at al. used a much simpler proximal cue that cannot exclude success based on stimulus enhancement rather than an understanding of the cue's communicative nature. We therefore addressed this issue by testing shelter dogs' abilities to use a range of proximal and distal human communicative cues in a standard object-choice task. We found shelter dogs could use proximal cues that may involve stimulus enhancement, but they continuously failed to use distal cues that excluded this possibility. Object-choice tasks with dogs typically involve non-vocalised human cues. We tested if vocalising would help shelter dogs to use distal cues. We found shelter dogs could use a vocalised distal continuous cue when the subject's name was called during cue presentation. It is therefore possible that vocalised cues help domesticated dogs learn about non-vocalised human communicative cues. Overall our results do not support that domesticated dogs' understanding of human communicative cues is a direct result of the domestication process.}, } @article {pmid30843578, year = {2019}, author = {Smith, TO and Collier, T and Sheehan, KJ and Sherrington, C}, title = {The uptake of the hip fracture core outcome set: analysis of 20 years of hip fracture trials.}, journal = {Age and ageing}, volume = {48}, number = {4}, pages = {595-598}, doi = {10.1093/ageing/afz018}, pmid = {30843578}, issn = {1468-2834}, mesh = {Activities of Daily Living ; Arthralgia/epidemiology/etiology ; Clinical Trials as Topic/methods/statistics & numerical data ; Hip Fractures/mortality/surgery/*therapy ; Humans ; Mobility Limitation ; Outcome Assessment, Health Care/*statistics & numerical data ; Quality of Life ; Registries ; Treatment Outcome ; }, abstract = {BACKGROUND: clinical trials test the effectiveness or efficacy of treatments. It is important that researchers evaluate interventions with the most meaningful outcome measures. The 2014 hip fracture core outcome set recommended that mortality, mobility, pain, activities of daily living and health-related quality of life (HRQOL) should be assessed in all trials of patient with hip fracture. The purpose of this analysis was to determine the uptake of these recommendation.

METHODS: all trials registered from 1997 to 2018 recruiting participants following hip fracture were identified from the ClinicalTrials.gov trials registry. The frequency of each core domain adopted annually were assessed.

RESULTS: 311 trials were identified and analysed. On analysing trial registries for years which presented a minimum of 10 registrations, full core outcome set adoption ranged from 0% (2017; 2018) to 24% (2009). Mortality and mobility were the most consistently reported domains (mortality: 27% (2017) to 56% (2011); mobility: 36% (2015) to 60% (2004)). In contrast, pain and HRQOL were least reported (pain: 14% (2017) to 61% (2015); HRQOL: 10% (2010) to 11% (2008)). There was no clear change in core outcome domain set adoption following the publication of Hayward et al.'s (2014) core outcome set.

CONCLUSIONS: there has been limited adoption of the hip fracture core outcome set from its publication in 2014. Further consideration to improve implementation is required to improved uptake.}, } @article {pmid30836831, year = {2020}, author = {Taubner, S}, title = {Parental mentalizing as a key resource for difficult transitions.}, journal = {Attachment & human development}, volume = {22}, number = {1}, pages = {46-50}, doi = {10.1080/14616734.2019.1589060}, pmid = {30836831}, issn = {1469-2988}, mesh = {*Child Development ; Fathers/psychology ; Humans ; Infant ; *Mentalization ; Mothers/psychology ; *Object Attachment ; Parenting/*psychology ; Parents/*psychology ; Sex Factors ; Socioeconomic Factors ; }, abstract = {This commentary on Ruiz et al.'s study focuses on the relevance of parental mentalizing for child development within a transactional framework. This view takes into account what kind of challenges in the parent, in the infant, or in the interaction have effects on child development and if this mediated by parental mentalizing. Differences between maternal and paternal mentalizing seem unrelated to the general level of reflective functioning but strongly influenced by social roles of parents. However, more sophisticated measures of mentalizing are needed to better understand subtle problems with regard to a dimensional and multifaceted model of mentalizing as well as interactional processes. To master the transition to parenthood in challenging circumstances such as preterm birth, it would be especially valuable to know if one parent's lower mentalizing can be counterbalanced by higher mentalizing in the other parent.}, } @article {pmid30833677, year = {2020}, author = {Latzman, RD and Patrick, CJ and Lilienfeld, SO}, title = {Heterogeneity matters: implications for Poeppl et al.'s (2019) meta-analysis and future neuroimaging research on psychopathy.}, journal = {Molecular psychiatry}, volume = {25}, number = {12}, pages = {3123-3124}, pmid = {30833677}, issn = {1476-5578}, mesh = {*Antisocial Personality Disorder ; Brain/diagnostic imaging ; Humans ; *Neuroimaging ; }, } @article {pmid30829509, year = {2019}, author = {Estrada, E and Ferrer, E and Román, FJ and Karama, S and Colom, R}, title = {Time-lagged associations between cognitive and cortical development from childhood to early adulthood.}, journal = {Developmental psychology}, volume = {55}, number = {6}, pages = {1338-1352}, pmid = {30829509}, issn = {1939-0599}, support = {N01 NS092315/NS/NINDS NIH HHS/United States ; N01 MH090002/MH/NIMH NIH HHS/United States ; N01 NS092320/NS/NINDS NIH HHS/United States ; N01 HD023343/HD/NICHD NIH HHS/United States ; N01 NS092317/NS/NINDS NIH HHS/United States ; N01 NS092319/NS/NINDS NIH HHS/United States ; N01 NS092316/NS/NINDS NIH HHS/United States ; N01 NS092314/NS/NINDS NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Brain ; Cerebral Cortex/*growth & development ; Child ; Cognition/*physiology ; Female ; Humans ; Intelligence Tests/statistics & numerical data ; Longitudinal Studies ; *Magnetic Resonance Imaging ; Male ; Young Adult ; }, abstract = {Throughout childhood and adolescence, humans experience marked changes in cortical structure and cognitive ability. Cortical thickness and surface area, in particular, have been associated with cognitive ability. Here we ask the question: What are the time-related associations between cognitive changes and cortical structure maturation. Identifying a developmental sequence requires multiple measurements of these variables from the same individuals across time. This allows capturing relations among the variables and, thus, finding whether (a) developmental cognitive changes follow cortical structure maturation, (b) cortical structure maturation follows cognitive changes, or (c) both processes influence each other over time. Four hundred and thiry children and adolescents (age range = 6.01-22.28 years) completed the Wechsler Abbreviated Scale of Intelligence battery and were MRI scanned at 3 time points separated by ≈2 years (Mage T1 = 10.60, SD = 3.58; Mage T2 = 12.63, SD = 3.62; Mage T3 = 14.49, SD = 3.55). Latent change score models were applied to quantify age-related relationships among the variables of interest. Our results indicate that cortical and cognitive changes related to each other reciprocally. Specifically, the magnitude or rate of the change in each variable at any occasion-and not the previous level-was predictive of later changes. These results were replicated for brain regions selected according to the coordinates identified in the Basten et al.'s (2015) meta-analysis, to the parieto-frontal integration theory (Jung & Haier, 2007) and to the whole cortex. Potential implications regarding brain plasticity and cognitive enhancement are discussed. (PsycINFO Database Record (c) 2019 APA, all rights reserved).}, } @article {pmid30829055, year = {2019}, author = {Jiang, M and Yang, J and Song, Y and Zheng, J and Li, X and Yang, G and Ma, Y and Xu, P and Zhang, Z and Pan, X and Wang, Y}, title = {Social support, stigma, and the mediating roles of depression on self-reported medication adherence of HAART recipients in China.}, journal = {AIDS care}, volume = {31}, number = {8}, pages = {942-950}, doi = {10.1080/09540121.2019.1587360}, pmid = {30829055}, issn = {1360-0451}, mesh = {Adolescent ; Adult ; Aged ; *Antiretroviral Therapy, Highly Active ; China/epidemiology ; Cross-Sectional Studies ; Depression/diagnosis/*epidemiology/psychology ; Female ; HIV Infections/*drug therapy/epidemiology/*psychology ; Humans ; Male ; Medication Adherence/psychology ; Middle Aged ; Models, Psychological ; *Self Efficacy ; Self Report ; *Social Stigma ; *Social Support ; *Assessment of Medication Adherence ; }, abstract = {Discrimination of people living with HIV/AIDS (PLWHA) is a persistent issue in China, which affects their psychological health. However, the association between psychological factors and adherence to highly active antiretroviral therapy (HAART) has not been systematically investigated before. Therefore, this study examined the impact of social support, depression, and medication-taking self-efficacy on ART adherence among PLWHA based on Cha et al.'s model, and included "stigma" to the original model to explain the psychological mechanism. Of the 504 participants receiving HAART, 37.8% had mild-to-severe depression. According to structural equation modeling, social support was directly associated with depression, stigma, and adherence; depression partially mediated the positive relationship between social support and adherence self-efficacy and the negative association between stigma and self-efficacy. The modified and extended Cha et al.'s model had a satisfactory fit. Interventions to improve mental health through mental health services, social support, and enhancement of adherence self-efficacy beliefs are required.}, } @article {pmid30820116, year = {2019}, author = {Khalid, F and Chong, LA}, title = {National Pediatric Palliative Care Needs from Hospital Deaths.}, journal = {Indian journal of palliative care}, volume = {25}, number = {1}, pages = {135-141}, pmid = {30820116}, issn = {0973-1075}, abstract = {OBJECTIVE: The objective of this study was to estimate palliative care needs and to describe the cohort of children with life-limiting illnesses (LLI) dying in hospitals.

DESIGN: This study was a retrospective cohort study. The national hospital admissions database was reviewed and children who had died who had life-limiting illnesses were identified.

SETTING: This study was conducted at Ministry of Health hospitals, Malaysia.

PATIENTS: Children aged 18 years and below who had died between January 1, 2012 and December 31, 2014.

MAIN OUTCOME MEASURES: Life-limiting diagnoses based on Hain et al.'s directory of LLI or the ACT/RCPCH categories of life-limiting disease trajectories.

RESULTS: There were 8907 deaths and 3958 (44.4%) were that of children with LLI. The majority, 2531 (63.9%) of children with LLI were neonates, and the most common diagnosis was extreme prematurity <28 weeks with 676 children (26.7%). For the nonneonatal age group, the median age at admission was 42 months (1-216 months). A majority, 456 (32.0%) had diagnoses from the ICD-10 chapter "Neoplasms" followed by 360 (25.3%) who had a diagnoses from "Congenital malformations, deformations, and chromosomal abnormalities" and 139 (9.7%) with diagnoses from "Disease of the nervous system." While a majority of the terminal admissions were to the general ward, there were children from the nonneonatal age group, 202 (14.2%) who died in nonpediatric wards.

CONCLUSION: Understanding the characteristics of children with LLI who die in hospitals could contribute toward a more efficient pediatric palliative care (PPC) service development. PPC service should include perinatal and neonatal palliative care. Palliative care education needs to extend to nonpediatric healthcare providers who also have to manage children with LLI.}, } @article {pmid30816742, year = {2020}, author = {Yoon, S and Verona, E and Schlauch, R and Schneider, S and Rottenberg, J}, title = {Why do depressed people prefer sad music?.}, journal = {Emotion (Washington, D.C.)}, volume = {20}, number = {4}, pages = {613-624}, doi = {10.1037/emo0000573}, pmid = {30816742}, issn = {1931-1516}, mesh = {Adult ; Depressive Disorder, Major/*psychology ; Emotions/*physiology ; Female ; Humans ; Music/*psychology ; Sadness/*psychology ; Young Adult ; }, abstract = {One of the cardinal symptoms of major depressive disorder (MDD) is persistent sadness. Do people with MDD actually prefer sad stimuli, potentially perpetuating their depression? Millgram, Joormann, Huppert, and Tamir (2015) observed such preferences and interpreted them as reflecting a maladaptive emotion regulatory goal to upregulate sad feelings. We assessed emotional music choice among both those with MDD and healthy controls (HC), and assessed the reasons for music preferences in these two groups. Seventy-six female participants (38 per group) completed two tasks: (1) Millgram et al.'s (2015) music task wherein participants listened to happy, neutral, and sad music excerpts and chose the one they wanted to listen to most, and (2) a novel Emotional Music Selection Task (EMST) wherein participants chose preferred music clips, varying in emotion and energy level, in paired-choice trials. In the replication music task, MDD people were more likely to choose sad music. However, inconsistent with any motivation to upregulate sadness, people with MDD reported that they chose sad music because it was low in energy levels (e.g., relaxing). EMST results revealed that MDD people had a stronger preference for both low energy and sad music, relative to HC. The strong appeal of sad music to people with MDD may be related to its calming effects rather than any desire to increase or maintain sad feelings. (PsycInfo Database Record (c) 2020 APA, all rights reserved).}, } @article {pmid30814889, year = {2018}, author = {Gürpinar, ÖA and Kubat, E and Onur, MA}, title = {Hyperoxic or hypoxic environment?.}, journal = {Turkish journal of biology = Turk biyoloji dergisi}, volume = {42}, number = {4}, pages = {267}, pmid = {30814889}, issn = {1303-6092}, abstract = {We read the article by Khan et al. (2017) in a recent issue of this journal with great interest. We would like to congratulate the authors for this report. In the article, the authors focused primarily on the characteristics of adiposederived mesenchymal stem cells (Ad-MSCs) by altering culture environment. The results of the study showed that culture medium containing 0.5% gelatin enhanced the proliferation rate, induced immunosuppression, and activated BMP-7 and the wnt/AXIN/β-catenin pathway in Ad-MSCs. However, we believe there is a misunderstanding in the introduction section of the article. A review of the literature shows that certain characteristics of MSCs can be modified with altered culture environments or preconditioned incubation processes. Khan et al. also cited a review published by Song et al. in 2010, as mentioned in the Introduction. This study indicated that preconditioning MSCs under hypoxic conditions enhanced the activity of the MSCs, suggesting a new perspective for the cellular treatment of cardiac tissue damages. In this review, hypoxic conditions were shown to have cytoprotective effects for MSCs, regulated paracrine factors, and increased the VEGF secretion (Song et al., 2010). Likewise, several studies with different designs in the literature yielded similar results (Kadle et al., 2016; Ciria et al., 2017). Therefore, we believe that the term "hyperoxic conditions" mentioned in the introduction of Khan et al.'s article (in citation to the study of Song et al.) is confusing. We recommend that this erroneous term be corrected to prevent any misunderstanding for the readers. We believe that the authors of the article would regard our opinion as a contribution.}, } @article {pmid30809074, year = {2019}, author = {Lin, F and Chen, GB}, title = {Sun et al.'s study led to the underperformance of EigenGWAS.}, journal = {Heredity}, volume = {123}, number = {2}, pages = {283-284}, pmid = {30809074}, issn = {1365-2540}, support = {31871707//National Natural Science Foundation of China (National Science Foundation of China)/International ; }, mesh = {Benchmarking/methods ; Genome-Wide Association Study/*methods ; Humans ; }, } @article {pmid30804593, year = {2019}, author = {Siddiqi, FA and Masood, T and Osama, M and Azim, ME and Babur, MN}, title = {Common balance measures and fall risk scores among older adults in Pakistan: Normative values and correlation.}, journal = {JPMA. The Journal of the Pakistan Medical Association}, volume = {69}, number = {2}, pages = {246-249}, pmid = {30804593}, issn = {0030-9982}, mesh = {*Accidental Falls/prevention & control/statistics & numerical data ; Aged ; Correlation of Data ; Cross-Sectional Studies ; Female ; Geriatric Assessment/*methods ; Humans ; Independent Living/statistics & numerical data ; Male ; Middle Aged ; Mobility Limitation ; Pakistan ; *Physical Functional Performance ; *Postural Balance ; Research Design ; Risk Assessment/*methods ; Risk Factors ; }, abstract = {The objective of this study was to assess the balance and fall risk among the community dwelling healthy older adults in Pakistan and to determine the correlation between balance measures and fall risk, for which a crosssectional correlation study was conducted at Foundation University Islamabad and Fauji Foundation Hospital from March 2016 to February 2017. A total of 77 individuals over 50 years were included via convenience sampling. I n di vi d u al s w i t h he a r i ng /v is ua l an d c o gn it ive impairments, infections, and orthopaedic and severe comorbid conditions were excluded. Data collection tools included Berg Balance Scale (BBS), Timed Up and Go (TUG) test, Functional Reach Test (FRT) and Fall Risk Score (FRS). Independent t-test and Bivariate Pearson Correlation (CI=95%, P<0.05) were used for analysis. Mean value of the BBS, FRS, TUG and FRT was 41.36±2.96, 3.40±1.47, 15.90±2.68 and 13.34±3.45 respectively. Age had a significant (p<0.05) positive correlation with FRS and negative correlation with BBS. A significant correlation (P<0.05) was found only between FRT & TUG and TUG & BBS.}, } @article {pmid30799069, year = {2019}, author = {Delazer, M and Zamarian, L}, title = {A commentary on Popescu et al.'s paper on the brain-structural correlates of mathematical expertise.}, journal = {Cortex; a journal devoted to the study of the nervous system and behavior}, volume = {117}, number = {}, pages = {417-420}, doi = {10.1016/j.cortex.2019.01.023}, pmid = {30799069}, issn = {1973-8102}, mesh = {*Brain ; Mathematics ; }, } @article {pmid30772739, year = {2019}, author = {Currier, JM and Foster, JD and Witvliet, CV and Abernethy, AD and Root Luna, LM and Schnitker, SA and VanHarn, K and Carter, J}, title = {Spiritual struggles and mental health outcomes in a spiritually integrated inpatient program.}, journal = {Journal of affective disorders}, volume = {249}, number = {}, pages = {127-135}, doi = {10.1016/j.jad.2019.02.012}, pmid = {30772739}, issn = {1573-2517}, mesh = {Adult ; Antidepressive Agents/*therapeutic use ; Christianity ; Depressive Disorder, Major/psychology/*therapy ; Female ; Humans ; Inpatients ; Male ; *Mental Health ; Middle Aged ; Morals ; Patient Care Team ; *Psychotherapy ; *Spirituality ; }, abstract = {BACKGROUND: Persons contending with serious mental health difficulties often experience struggles with religious faith and/or spirituality that may also demand clinical attention. However, research has not examined the relative importance of specific forms of spiritual struggles in mental health status or treatment outcomes of psychiatric patients.

METHODS: Focusing on 217 adults who completed a spiritually integrated inpatient program, this study examined (1) which struggles in Exline et al.'s (2014) framework (Divine, Morality, Ultimate Meaning, Interpersonal, Demonic, and Doubting) represented the most salient indicators of major depressive disorder (MDD) symptomatology and positive mental health (PMH) and (2) whether alleviation of these struggles predicted improvements in patients' mental health status over the treatment period.

RESULTS: Greater severity of spiritual struggles was generally associated with worse MDD symptomatology and less PMH at intake and discharge. However, when weighing the role of varying forms of struggles, issues with ultimate meaning emerged as a salient indicator of mental health status at the two assessments as well as longitudinal changes in both MDD symptomatology and PMH.

LIMITATIONS: This sample was recruited from acute stabilization units in a single spiritually integrated behavioral health center with a general affiliation with Christianity. Hence, treatment periods were relatively brief in some cases and findings might not generalize to other psychiatric programs or settings.

CONCLUSIONS: Findings highlight the utility of assessing prominent forms of spiritual distress for planning and delivering psychosocial interventions, particularly with respect to issues related to a perceived absence of ultimate meaning in life.}, } @article {pmid30768394, year = {2019}, author = {Rogers, SJ and Estes, A and Lord, C and Munson, J and Rocha, M and Winter, J and Greenson, J and Colombi, C and Dawson, G and Vismara, LA and Sugar, CA and Hellemann, G and Whelan, F and Talbott, M}, title = {A Multisite Randomized Controlled Two-Phase Trial of the Early Start Denver Model Compared to Treatment as Usual.}, journal = {Journal of the American Academy of Child and Adolescent Psychiatry}, volume = {58}, number = {9}, pages = {853-865}, pmid = {30768394}, issn = {1527-5418}, support = {R01 MH081757/MH/NIMH NIH HHS/United States ; }, mesh = {Autism Spectrum Disorder/diagnosis/prevention & control/*therapy ; Child, Preschool ; Early Intervention, Educational/*methods ; Family Therapy/*methods ; Female ; Humans ; Infant ; Male ; Models, Psychological ; *Parent-Child Relations ; Parents/*education/psychology ; Risk ; Time Factors ; United States ; }, abstract = {OBJECTIVE: This single-blind, randomized, multisite, intent-to-treat study was designed to replicate and extend Dawson et al.'s (Pediatrics. 2010;125: e17-e23) randomized controlled trial testing the effects of the Early Start Denver Model (ESDM), an intensive play- and routines-based intervention delivered in natural settings.

METHOD: A randomized controlled trial was conducted at 3 universities. One hundred eighteen children 14 to 24 months old with autism spectrum disorder were enrolled and randomly assigned to ESDM or community interventions for 27 months. Eighty-one children completed the full treatment course and all assessments; data from all 118 children were used in analyses. Children assigned to the ESDM intervention received 3 months of weekly parent coaching followed by 24 months of 15 hour per week (on average) 1:1 treatment weekly on average in homes or daycare settings from supervised therapy assistants while parents received coaching 4 hours monthly from a certified ESDM therapist.

RESULTS: For the primary analyses, there were time-by-group and time-by-group-by-site interactions for language outcome. In the significant 3-way interaction involving site, 2 sites showed a significant ESDM advantage and the third site showed no significant group differences. In the planned 2-way analysis that pooled data across all 3 sites, there was a significant advantage found for the ESDM group. For the secondary analyses, there were no significant differences between the ESDM and community groups involving developmental quotient, autism severity, or adaptive behavior. The treatment effect of group on language outcomes was not moderated by baseline developmental quotient, autism severity, or language.

CONCLUSION: Results of the primary analysis provide a partial replication of Dawson et al.'s 2010 language findings.

Intensive Intervention for Toddlers with Autism; https://clinicaltrials.gov/; NCT00698997.}, } @article {pmid30763597, year = {2019}, author = {Rashmi, G and Michael, Z and Fabien, E}, title = {Response to Letter to Editor: Gulati et al.'s article "Presetting ECG electrodes for earlier heart rate detection in the delivery room.": Prehospital use of ECG electrodes by nonmedical emergency professionals: An additional source of help during unexpected out-of-hospital births.}, journal = {Resuscitation}, volume = {137}, number = {}, pages = {242-243}, doi = {10.1016/j.resuscitation.2018.11.023}, pmid = {30763597}, issn = {1873-1570}, mesh = {Humans ; Infant, Newborn ; Pregnancy ; *Delivery Rooms ; Electrocardiography ; Electrodes ; *Emergency Medical Services ; Heart Rate ; Female ; }, } @article {pmid30746045, year = {2018}, author = {Hernández-Bendezú, MDC and Arias-Peña, MY and Torres-Fraga, MG and Carrillo-Alduenda, JL}, title = {Quality of an ambulatory monitoring technique for diagnosing obstructive sleep apnea under conditions of limited resources.}, journal = {Sleep science (Sao Paulo, Brazil)}, volume = {11}, number = {4}, pages = {269-273}, pmid = {30746045}, issn = {1984-0659}, abstract = {OBJECTIVES: To: 1) evaluate the quality of an ambulatory monitoring technique for diagnosing Obstructive Sleep Apnea Syndrome (OSAS) while patients move through the city; and 2) identify factors that lead to data loss.

METHODS: Clinical histories were reviewed and ambulatory portable monitorings of adults with high pretest probability for OSAS were included, the signals monitored were pulse oximetry, heart rate, nasal pressure, snoring, chest band and body position. The equipment was connected from 14:00-20:00 h and then patients moved through the city turning it off and on at home. Results were analyzed visually to record all the minutes lost. A good-quality study was defined as recording time 240 min and signal loss <20%. A cost/benefit analysis was performed using Golpe et al.'s methodology.

RESULTS: A total of 70 recordings were analyzed. Most subjects were obese men with severe OSAS. Signal quality was determined to be good with a median signal loss of 4.9 min (0-405) that represented 1% (0-99) of total recording time. The signal lost most often was pulse oximetry at 1.8 min (0-403, p=0.0001). Of the 70 studies performed, 57 (81%) met the definition of good quality, while 13 (19%) had to be repeated. Men lost the pulse oximetry signal more often than women. This technique could represent savings of 65-75%.

CONCLUSIONS: Placing a portable OSAS monitor during the day while patients move around the city turning it on and off at home does not affect the quality of the study results obtained and is a cost-effective method.}, } @article {pmid30742345, year = {2019}, author = {Conway, CM and Arciuli, J and Lum, JAG and Ullman, MT}, title = {Seeing problems that may not exist: A reply to West et al.'s (2018) questioning of the procedural deficit hypothesis.}, journal = {Developmental science}, volume = {22}, number = {4}, pages = {e12814}, pmid = {30742345}, issn = {1467-7687}, support = {R01 DC012037/DC/NIDCD NIH HHS/United States ; R21 HD087088/HD/NICHD NIH HHS/United States ; }, mesh = {Humans ; Language ; *Language Development Disorders ; Language Tests ; *Learning Disabilities ; }, } @article {pmid30734349, year = {2019}, author = {Chang, HY and Lee, IC and Chu, TL and Liu, YC and Liao, YN and Teng, CI}, title = {The role of professional commitment in improving nurses' professional capabilities and reducing their intention to leave: Two-wave surveys.}, journal = {Journal of advanced nursing}, volume = {75}, number = {9}, pages = {1889-1901}, doi = {10.1111/jan.13969}, pmid = {30734349}, issn = {1365-2648}, support = {CMRPD3F0031//Chang Gung Memorial Hospital/ ; }, mesh = {Adult ; *Attitude of Health Personnel ; Cross-Sectional Studies ; Female ; Humans ; *Job Satisfaction ; Male ; Middle Aged ; *Motivation ; Nursing Staff, Hospital/*psychology/*statistics & numerical data ; Personnel Turnover/*statistics & numerical data ; Professional Role/*psychology ; Surveys and Questionnaires ; Taiwan ; }, abstract = {BACKGROUND: Social cognitive career theory (SCCT) can explain the mechanism underlying the formulation of nurse turnover intention. However, little is known about the role of professional commitment in such a mechanism.

AIMS: The aim of this study was to explore how elements of SCCT have an impact on the three aspects of professional commitment and thus nurses' intention to leave the profession.

DESIGN: This study used surveys to collect two-wave data.

METHODS: The participants were sampled in all available units of a major medical centre in 2017. By using proportionate random sampling methods, we successfully followed up a representative sample of 524 full-time nurses. Most participants (98.1%) were female. Items came from Cunningham et al.'s Self-Efficacy Scale, Outcome Expectations Scale, Human Capital Scale and Vocational Interest Scale; Meyer et al.'s Professional Commitment Scale; and Teng et al.'s Turnover Intention Scale. Structural equation modelling was used to test the hypotheses.

RESULTS: Self-efficacy was positively related to outcome expectation. Outcome expectation was positively related to career interest. Career interest was positively related to affective professional commitment. Human capital was positively related to normative professional commitment. Affective professional commitment was positively related to intention to improve professional capabilities, which was further negatively related to intention to leave the profession.

CONCLUSION: Aspects of professional commitment are important process variables in the impact of self-efficacy and outcome expectation on nurses' turnover intention.}, } @article {pmid30732309, year = {2019}, author = {Long, S and Qin, Y and Chen, H and Wu, X and Li, M and Tang, X and Wen, T}, title = {Two-stage excitation model of diode pumped rare gas atoms lasers.}, journal = {Optics express}, volume = {27}, number = {3}, pages = {2771-2782}, doi = {10.1364/OE.27.002771}, pmid = {30732309}, issn = {1094-4087}, abstract = {Diode pumped rare gas atoms lasers (DPRGLs) are potential candidates of the high-energy lasers, due to the advantages of high laser power and high optical conversion efficiency. In this paper, a two-stage excitation model of DPRGLs is established including gas discharge excitation and semiconductor laser pump to study energy loss mechanism and obtain total efficiency. The results of numerical simulation agree well with those of Rawlins et al.'s experiment. Through parameter optimization, the total efficiency and optical conversion efficiency reach 51.5% and 62.7% respectively, at pump intensity of 50 kW/cm[2] and reduced electric field of 8 Td. Parameter optimization of two-stage excitation lasers is theoretically studied, which is significant for the DPRGLs design with high total efficiency.}, } @article {pmid30723528, year = {2019}, author = {Golozar, A and Schoendorf, J}, title = {RE: "An Estimation of the Risk of Pseudotumor Cerebri Among Users of the Levonorgestrel Intrauterine Device".}, journal = {Neuro-ophthalmology (Aeolus Press)}, volume = {43}, number = {1}, pages = {67-69}, pmid = {30723528}, issn = {0165-8107}, abstract = {The current letter to the editor describes some of the limitations of Valenzuela et al.'s study on the association between levonorgestrel-releasing intrauterine system use and pseudotumor cerebri/idiopathic intracranial hypertension and further reinforces the authors' interpretations of the findings.}, } @article {pmid30681951, year = {2019}, author = {Hirschovits-Gerz, T and Kuussaari, K and Stenius, K and Tammi, T}, title = {Estimating the Needs of Substance Problem Use Services: An Exercise in Seven Finnish Municipalities Using Nationally Collected, Municipal-Level Survey and Register Data†.}, journal = {Journal of studies on alcohol and drugs. Supplement}, volume = {Sup 18}, number = {18}, pages = {76-86}, pmid = {30681951}, issn = {1946-5858}, mesh = {Cities/epidemiology ; Cross-Sectional Studies ; *Data Analysis ; Finland/epidemiology ; Health Services Needs and Demand/*trends ; Humans ; *Registries ; Statistics as Topic/trends ; Substance-Related Disorders/*epidemiology/*therapy ; *Surveys and Questionnaires ; }, abstract = {OBJECTIVE: The needs of substance problem use services (SPUSs) should ideally be assessed locally to support the provision of appropriate, cost-effective services for the population. In this article we present a model for estimating the adult population's potential needs for and actual use of SPUSs. We used Finnish survey and register data as material for a qualitative assessment. The purpose of our article is to contribute to a discussion on the dimensions of assessment of the need for SPUSs at a local level.

METHOD: Seven Finnish municipalities were chosen as examples. The need for SPUSs was assessed by freely available register and survey data of the use of services, substance use and problem use, side effects of use, and lack of social support. Babor et al.'s (2008) description of links between the use of services and need for treatment, in terms of substance use and general social conditions, and Ritter's (2014a) set of methods for assessing the need for treatment are used as theoretical background.

RESULTS: The number of people using SPUSs varied from one municipality to the next. The local service system policy and the general well-being of the population have a remarkable role in the use of SPUSs.

CONCLUSIONS: Estimations of need and demand with indicators can be useful for local treatment system policy but must be interpreted with thorough knowledge of the local treatment and social handling resources and general social situation. Comparisons between different local areas should be made with caution.}, } @article {pmid30661201, year = {2019}, author = {Leng, J and Lui, F and Huang, X and Breitbart, W and Gany, F}, title = {Patient perspectives on adapting meaning-centered psychotherapy in advanced cancer for the Chinese immigrant population.}, journal = {Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer}, volume = {27}, number = {9}, pages = {3431-3438}, pmid = {30661201}, issn = {1433-7339}, support = {U54 CA137788/CA/NCI NIH HHS/United States ; 3R01CA128134-05S1/NH/NIH HHS/United States ; R03CA178124-01A1/NH/NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; U54 CA132378/CA/NCI NIH HHS/United States ; R01 CA128134/CA/NCI NIH HHS/United States ; R03 CA202515/CA/NCI NIH HHS/United States ; R03 CA178124/CA/NCI NIH HHS/United States ; R21 NR019188/NR/NINR NIH HHS/United States ; T32 CA009461/CA/NCI NIH HHS/United States ; UL1 TR002384/TR/NCATS NIH HHS/United States ; }, mesh = {*Adaptation, Psychological ; Adult ; Aged ; Anxiety/*therapy ; Asian People ; Emigrants and Immigrants/*psychology ; Female ; Humans ; Language ; Middle Aged ; Neoplasms/*psychology ; *Psychosocial Support Systems ; Psychotherapy/*methods ; Religion ; United States ; }, abstract = {The Chinese immigrant community faces multiple obstacles to effective cancer support and psychosocial care post diagnosis. Meaning-centered psychotherapy (MCP) is an empirically based treatment (EBT) that has been found to significantly reduce psychological distress while increasing spiritual well-being and a sense of meaning and purpose in life in patients with advanced cancer. However, it has not yet been adapted for Chinese immigrants who have unique linguistic and cultural needs. This study presents a community needs assessment to inform the cultural adaptation of MCP for Chinese patients with advanced cancer using Bernal et al.'s ecological validity model and the cultural adaptation process model of Domenech-Rodriquez and Weiling. Interviews were conducted until saturation with 12 Chinese immigrants with advanced cancer to determine the community's needs and preferences regarding the MCP intervention. Transcripts were translated and analyzed using Atlas.ti and six frequently occurring themes were identified: Coping; End of Life; Family; Culture, Religion, and Language; Immigration; and Specific Adaptations to MCP. Sociocultural values, beliefs, and practices such as filial piety and the use of Traditional Chinese Medicine (TCM) should be considered when adapting EBTs for Chinese immigrant cancer patients.}, } @article {pmid30659438, year = {2019}, author = {Kim, HJ}, title = {Response to Apóstolos et al.'s (2018) "Gender Identity and Sexual Function in 46,XX Patients with Congenital Adrenal Hyperplasia Raised as Males".}, journal = {Archives of sexual behavior}, volume = {48}, number = {3}, pages = {675-677}, doi = {10.1007/s10508-018-1386-1}, pmid = {30659438}, issn = {1573-2800}, mesh = {*Adrenal Hyperplasia, Congenital ; *Disorders of Sex Development ; Female ; Gender Identity ; Humans ; Male ; }, } @article {pmid30658854, year = {2019}, author = {On Behalf Of Ema, }, title = {Reply to Joe O'Sullivan, Daniel Heinrich, Nicholas D. James, et al.'s Letter to the Editor re: The Case Against the European Medicines Agency's Change to the Label for Radium-223 for the Treatment of Metastatic Castration-resistant Prostate Cancer. Eur Urol 2019;75:e51-2.}, journal = {European urology}, volume = {75}, number = {3}, pages = {e53}, doi = {10.1016/j.eururo.2018.11.053}, pmid = {30658854}, issn = {1873-7560}, mesh = {Abiraterone Acetate ; Humans ; Male ; *Neoplasms, Second Primary ; *Prostatic Neoplasms ; *Prostatic Neoplasms, Castration-Resistant ; *Radium ; }, } @article {pmid30657407, year = {2019}, author = {Wasserman, M and Palacios, MG and Grajales, AG and Wilson, M and McDade, C and Farkouh, R}, title = {Comment on Gomez et. al. "Response to article by Wasserman et. al. (2018) 'Modelling the sustained use of the 13-valent pneumococcal conjugate vaccine compared to switching to the 10-valent vaccine in Mexico'".}, journal = {Human vaccines & immunotherapeutics}, volume = {15}, number = {3}, pages = {572-574}, pmid = {30657407}, issn = {2164-554X}, mesh = {Cost-Benefit Analysis ; Humans ; Mexico ; *Pneumococcal Infections ; Pneumococcal Vaccines ; Vaccines, Conjugate ; }, abstract = {In a recent Letter, Gomez et. al. provided a critique of our original analysis estimating the clinical and economic impact of switching from the 13-valent (PCV13) to the 10-valent (PCV10) pneumococcal conjugate vaccine in Mexico. This comment addresses Gomez et. al.'s comments with additional information and clarifies potential misinterpretations.}, } @article {pmid30631714, year = {2018}, author = {Appianing, J and Van Eck, RN}, title = {Development and validation of the Value-Expectancy STEM Assessment Scale for students in higher education.}, journal = {International journal of STEM education}, volume = {5}, number = {1}, pages = {24}, pmid = {30631714}, issn = {2196-7822}, abstract = {BACKGROUND: Science, technology, engineering, and math (STEM) jobs are expected to make up a significant portion of the U.S. workforce. Unfortunately, the trend in retaining students in STEM majors has been going down. If higher education institutions are going to retain more students in STEM majors, it will be important to understand who leaves STEM fields and why. More than 32% of women college students who declare a STEM major are likely to switch to non-STEM majors before they graduate, whereas only 25% of their male counterparts do so, and women may be as much as 1.5 times more likely than men to leave STEM fields. Thus, women represent a significant potential source for increasing STEM majors. Research suggests that values and expectations are powerful predictors of motivation and persistence in a wide variety of activities, tasks, and careers. This paper describes the development and validation of an instrument to measure student motivation, particularly that of women, leading to decisions to persist in or switch out of collegiate STEM programs.

RESULTS: The Value-Expectancy STEM Assessment Scale (VESAS), adapted from the Values, Interest, and Expectations Scale, or VIES, was validated with 356 women students from a Midwestern research university as part of a larger study on the reasons that women persist or leave STEM majors. A confirmatory factor analysis suggested a two-factor model, which reflected the components of Eccles et al.'s expectancy-value model. Cronbach's alphas suggested that the VESAS subscales had high internal consistency. Statistically significant differences were found between STEM switchers and persisters on all of the VESAS subscales, thus lending additional support for the validity of the instrument.

CONCLUSIONS: The VESAS appears to be a valid scale for measuring female college students' value for and expectations regarding STEM majors. Suggestions are made for use of the VESAS in future studies to examine how motivations of women students enrolled in STEM programs change over time and to better understand when retention interventions might be needed and with whom.}, } @article {pmid30629706, year = {2019}, author = {Lee, RT and Perez, AD and Boykin, CM and Mendoza-Denton, R}, title = {On the prevalence of racial discrimination in the United States.}, journal = {PloS one}, volume = {14}, number = {1}, pages = {e0210698}, pmid = {30629706}, issn = {1932-6203}, mesh = {Black or African American ; Asian People ; Black People ; Female ; Hispanic or Latino ; Humans ; Male ; Prevalence ; Racism/*statistics & numerical data ; United States ; White People ; }, abstract = {Boutwell, Nedelec, Winegard, Shackelford, Beaver, Vaughn, Barnes, & Wright (2017) published an article in this journal that interprets data from the Add Health dataset as showing that only one-quarter of individuals in the United States experience discrimination. In Study 1, we attempted to replicate Boutwell et al.'s findings using a more direct measure of discrimination. Using data from the Pew Research Center, we examined a large sample of American respondents (N = 3,716) and explored the prevalence of discrimination experiences among various racial groups. Our findings stand in contrast to Boutwell et al.'s estimates, revealing that between 50% and 75% of Black, Hispanic, and Asian respondents (depending on the group and analytic approach) reported discriminatory treatment. In Study 2, we explored whether question framing affected how participants responded to Boutwell's question about experiencing less respect and courtesy. Regardless of question framing, non-White participants reported more experiences than White participants. Further, there was an interaction of participant race and question framing such that when participants were asked about experiences of less respect or courtesy broadly, there were no differences between non-White participants and White participants, but when they were asked about experiences that were specifically race-based, non-White participants reported more experiences than White participants. The current research provides a counterweight to the claim that discrimination is not a prevalent feature of the lives of minority groups and the serious implications this claim poses for research and public policy.}, } @article {pmid30623298, year = {2019}, author = {De Innocentiis, C and Ricci, F and Khanji, MY and Aung, N and Tana, C and Verrengia, E and Petersen, SE and Gallina, S}, title = {Authors' Reply to Kindermann et al.'s Comment on: "Athlete's Heart: Diagnostic Challenges and Future Perspectives".}, journal = {Sports medicine (Auckland, N.Z.)}, volume = {49}, number = {3}, pages = {495-496}, pmid = {30623298}, issn = {1179-2035}, support = {203553/Z/16/Z/WT_/Wellcome Trust/United Kingdom ; }, mesh = {*Athletes ; *Cardiomegaly ; Heart ; Humans ; }, } @article {pmid30611114, year = {2019}, author = {Viveiros, CJ and Darling, EK}, title = {Perceptions of barriers to accessing perinatal mental health care in midwifery: A scoping review.}, journal = {Midwifery}, volume = {70}, number = {}, pages = {106-118}, doi = {10.1016/j.midw.2018.11.011}, pmid = {30611114}, issn = {1532-3099}, mesh = {Adult ; Female ; Health Services Accessibility/*standards ; Humans ; Mental Health Services/*standards ; Midwifery/methods ; Nurse Midwives/*psychology ; *Perception ; Pregnancy ; Prenatal Care/methods/*standards ; }, abstract = {BACKGROUND: Despite greater contact with the healthcare system during the perinatal period, detection and treatment of perinatal mental health conditions remain suboptimal.

AIM: To explore midwives' and midwifery clients' perceptions of factors that impede access to perinatal mental health care in high resource settings.

DESIGN: Scoping review.

METHODS: Arksey and O'Malley's (2006) framework for scoping studies was employed. A systematic search of the literature was completed. Included publications must have (1) addressed barriers to obtaining perinatal mental health care; (2) been either peer-reviewed primary literature or grey literature; (3) if primary literature, the study explored the perceptions of midwives or those in midwifery care; and (4) if grey literature, the publication pertained directly to midwifery care. A study was excluded from the review if (1) it was published in a language other than English; (2) it was published prior to the year 2000; or (3) it took place in a country with a Maternal Mortality Ratio (MMR) above 14. Identified barriers were mapped onto Levesque et al.'s (2013) ten-dimension framework (five supply-side dimensions and five demand-side dimensions) on access to health care in order to determine which points along the chain to accessing perinatal mental health care were most adversely impacted.

FINDINGS: The search yielded a total of 1051 records, and twenty-six were included in the review (qualitative, quantitative, mixed methods, grey literature). Supply-side barriers included midwives' lack of PMH training, knowledge, and confidence, both generally and cross-culturally; inconsistent screening practices; broken referral pathways; lack of specialized services; underlying stigma toward those with PMH concerns; inefficiently long wait lists for services; and midwives' perception that PMH is not within their scope of practice. Demand-side barriers included emotional isolation and loneliness; normalization of PMH concerns as symptoms of pregnancy; cultural norms surrounding motherhood and mental health; and symptoms of PMH concerns as inhibiting the ability to obtain help.

Twenty-one out of the twenty-six publications included in this review identified problems at the very beginning of the care-accessing process, suggesting that PMH care is often unapproachable, or that people are unable to perceive their need for care in the first place. Midwives can help ameliorate these initial barriers by engaging in additional perinatal mental health training in order to increase knowledge and confidence; being aware of community resources and referral pathways; and initiating discussion about perinatal mental health with all clients with the help of a validated screening tool.}, } @article {pmid30610912, year = {2019}, author = {Leipold, S and Oderbolz, C and Greber, M and Jäncke, L}, title = {A reevaluation of the electrophysiological correlates of absolute pitch and relative pitch: No evidence for an absolute pitch-specific negativity.}, journal = {International journal of psychophysiology : official journal of the International Organization of Psychophysiology}, volume = {137}, number = {}, pages = {21-31}, doi = {10.1016/j.ijpsycho.2018.12.016}, pmid = {30610912}, issn = {1872-7697}, mesh = {Acoustic Stimulation/*methods/*psychology ; Adolescent ; Adult ; Electroencephalography/*methods ; Evoked Potentials, Auditory/*physiology ; Female ; Humans ; Male ; Music/*psychology ; Pitch Perception/*physiology ; Young Adult ; }, abstract = {Musicians with absolute pitch effortlessly identify the pitch of a sound without an external reference. Previous neuroscientific studies on absolute pitch have typically had small samples sizes and low statistical power, making them susceptible for false positive findings. In a seminal study, Itoh et al. (2005) reported the elicitation of an absolute pitch-specific event-related potential component during tone listening - the AP negativity. Additionally, they identified several components as correlates of relative pitch, the ability to identify relations between pitches. Here, we attempted to replicate the main findings of Itoh et al.'s study in a large sample of musicians (n = 104) using both frequentist and Bayesian inference. We were not able to replicate the presence of an AP negativity during tone listening in individuals with high levels of absolute pitch, but we partially replicated the findings concerning the correlates of relative pitch. Our results are consistent with several previous studies reporting an absence of differences between musicians with and without absolute pitch in early auditory evoked potential components. We conclude that replication studies form a crucial part in assessing extraordinary findings, even more so in small fields where a single finding can have a large impact on further research.}, } @article {pmid30606033, year = {2020}, author = {Waring, G and Kirk, S and Fallon, D}, title = {The impact of chronic non-specific cough on children and their families: A narrative literature review.}, journal = {Journal of child health care : for professionals working with children in the hospital and community}, volume = {24}, number = {1}, pages = {143-160}, doi = {10.1177/1367493518814925}, pmid = {30606033}, issn = {1741-2889}, mesh = {Child ; *Chronic Disease ; Cough/*etiology ; Humans ; Parents/*psychology ; Quality of Life/psychology ; Stress, Psychological/psychology ; }, abstract = {The aim of this article is to critically appraise and synthesize research that examines the impact chronic non-specific cough has on children and their families and to highlight gaps within the research. Chronic non-specific cough refers to a persistent cough without a specific diagnosis. While studies have begun to examine the impact on children and their families, this research has not been synthesized and appraised. A narrative literature review was undertaken. A comprehensive and systematic search was undertaken, using CINAHL, MEDLINE, British Nursing Index, PsycINFO, Cochrane Wiley Library and ASSIA databases. Studies were critically appraised for quality using the Hawker et al.'s appraisal tool. A narrative review of the findings was undertaken. Nine quantitative studies were included in the review. The article suggests that chronic non-specific cough affects the quality of life of both families and children, affecting quality of sleep, impacting upon participation in activities, causing emotional distress and creating substantial demand on the health service. Furthermore, the research highlighted the worries experienced by parents in relation to the cause of their child's cough. The review did not identify any qualitative research in this area and only one study collected data directly from children.}, } @article {pmid30596450, year = {2020}, author = {Brum, PS and Borella, E and Carretti, B and Sanches Yassuda, M}, title = {Verbal working memory training in older adults: an investigation of dose response.}, journal = {Aging & mental health}, volume = {24}, number = {1}, pages = {81-91}, doi = {10.1080/13607863.2018.1531372}, pmid = {30596450}, issn = {1364-6915}, mesh = {Aged ; Female ; Humans ; Learning ; Male ; Memory and Learning Tests ; *Memory, Short-Term ; Middle Aged ; }, abstract = {The WM training protocol proposed by Borella et al. found specific and transfer effects among seniors, however, the studies were carried out in the same socio-cultural context and variations in the procedure were never tested. The present study aimed at analyzing the efficacy of Borella et al.'s training, in terms of short and long-term benefits, in a different socio-cultural context (Study 1), and the effect of change in the training's length (duplicating the number of sessions (Study 2). Participants were randomly assigned to a trained group (N = 18 for Study 1, and N = 23 for Study 2) and active control group (N = 28 for Study 1, and N = 27 for Study 2), and evaluated at pre, post-test and six-month follow-up for verbal WM task (criterion task), and for visuospatial and verbal WM, inhibition, processing speed, executive function, and fluid intelligence measures (transfer tasks). The trained groups had higher performance in all tasks when compared with active control groups after training and at 6 month follow-up. The longer training (Study 2) generated similar gains as the original protocol, with some advantage in far transfer tasks at post-test and follow-up. Study limitations include the small sample sizes. In conclusion, this training was effective in a different socio-cultural context and adding three sessions to the protocol did not significantly change training impact.}, } @article {pmid30590447, year = {2019}, author = {Fong, Y and Huang, Y and Lemos, MP and Mcelrath, MJ}, title = {Response to Guo et al.'s Letter to the Editor.}, journal = {Biostatistics (Oxford, England)}, volume = {20}, number = {2}, pages = {363-365}, pmid = {30590447}, issn = {1468-4357}, support = {UM1 AI068618/AI/NIAID NIH HHS/United States ; S10 OD020069/OD/NIH HHS/United States ; R01 GM106177/GM/NIGMS NIH HHS/United States ; UM1 AI068635/AI/NIAID NIH HHS/United States ; R01 AI122991/AI/NIAID NIH HHS/United States ; }, } @article {pmid30589651, year = {2018}, author = {Mutumba, M and Musiime, V and Mugerwa, H and Nakyambadde, H and Gautam, A and Matama, C and Stephenson, R}, title = {Perceptions of HIV Self-Management Roles and Challenges in Adolescents, Caregivers, and Health Care Providers.}, journal = {The Journal of the Association of Nurses in AIDS Care : JANAC}, volume = {}, number = {}, pages = {}, doi = {10.1097/JNC.0000000000000007}, pmid = {30589651}, issn = {1552-6917}, abstract = {Self-management of HIV is a desirable goal for the millions of adolescent persons living with HIV (PLWH). Adolescent PLWH continue to experience poor HIV care outcomes, primarily due to poor rates of medication adherence and retention in care, highlighting a need to develop adolescent self-management skills. The aim of our study was to examine adolescent, caregiver, and health care provider perceptions of adolescent PLWH self-management roles, barriers, and facilitators. Swendeman et al.'s self-management framework for chronic diseases guided the analyses. Participant narratives highlighted perceptions of their responsibilities and related challenges with regard to self-management of HIV by adolescents. Our findings highlighted the complexity of HIV self-management for adolescents and underscored the need for multifaceted programs to strengthen adolescent-caregiver-health care provider partnerships in order to improve adolescent PLWH health and wellbeing.}, } @article {pmid30586379, year = {2018}, author = {Wilson, SP and Wilson, PN}, title = {Failure to demonstrate short-cutting in a replication and extension of Tolman et al.'s spatial learning experiment with humans.}, journal = {PloS one}, volume = {13}, number = {12}, pages = {e0208794}, pmid = {30586379}, issn = {1932-6203}, mesh = {Cues ; Female ; Humans ; Male ; Orientation, Spatial/*physiology ; Space Perception/*physiology ; Spatial Learning/*physiology ; Young Adult ; }, abstract = {Successful demonstrations of novel short-cut taking by animals, including humans, are open to interpretation in terms of learning that is not necessarily spatial. A classic example is that of Tolman, Ritchie, and Kalish (1946) who allowed rats to repeat a sequence of turns through the corridors of a maze to locate a food reward. When the entrance to the corridors was subsequently blocked and alternative corridors were made available, rats successfully selected the corridor leading most directly to the food location. However, the presence of a distinctive light above the goal, in both the training and testing phases, means that approach to the light as a beacon could have been the source of successful short-cutting. We report a replication of the experimental design of Tolman et al. with human participants who explored geometrically equivalent virtual environments. An experimental group, who followed the original procedure in the absence of any distinctive cues proximal to the goal, did not select the corridor which led most directly to the goal. A control group, who experienced a light above the goal during training and testing, were more likely to select a corridor which led in the direction of the goal. A second control group experienced the light above the goal during training, but in the test the location of this cue was shifted by 90° with respect to the start point of exploration. This latter group responded unsystematically in the test, neither selecting a corridor leading to the original goal location, nor one leading directly to the relocated light cue. The results do not support the hypothesis that travelling a multi-path route automatically leads to an integrated cognitive representation of that route. The data offer support for the importance of local cues which can serve as beacons to indicate the location of a goal.}, } @article {pmid30581073, year = {2018}, author = {Haseeb, M and Muzafar, K and Bhat, KA and Ghani, A and Singh, O}, title = {Plating the radial shaft on the lateral surface: An outcome study.}, journal = {Chinese journal of traumatology = Zhonghua chuang shang za zhi}, volume = {21}, number = {6}, pages = {360-365}, pmid = {30581073}, issn = {1008-1275}, mesh = {Adolescent ; Adult ; *Bone Plates ; Female ; Fracture Fixation, Internal/*methods ; Humans ; Male ; Middle Aged ; Prospective Studies ; Radius/*surgery ; Radius Fractures/*surgery ; Time Factors ; Treatment Outcome ; Young Adult ; }, abstract = {PURPOSE: Plate fixation is the gold standard for the treatment of displaced forearm shaft fractures in adults. Conventionally radial shaft fractures will be plated either on the volar surface or on the dorsal surface depending on which approach has been chosen. The lateral surface of the radius provides an even and uniformly curved area for placing a plate. It has the advantage of restoring and easy assessing the radial bow after surgery. We designed a prospective study to observe the outcome of lateral plating of radius shaft fractures.

METHODS: Nineteen patients were included in this study performed in Government Medical College, Jammu, India. Among them, 13 had fractures of both the forearm bones and 6 had isolated radial shaft fracture. Three patients had Galeazzi fracture dislocation. Fixation was done within 36 h of injury in all using 3.5 mm limited contact dynamic compression plate or locking compression plate applied to the lateral surface of the radius. Ulna was fixed in routine manner.

RESULTS: Union was achieved in 18 out of 19 patients, after a mean time of 17.44 weeks. According to Anderson et al.'s criteria, 12 patients had excellent results, 5 had satisfactory and 1 had unsatisfactory result. There was one failure (nonunion).

CONCLUSION: The outcomes including rate of union were comparable to those in the existing literature. Plating the radial shaft on the lateral surface is a viable alternative to volar or dorsal plating of the radius. Larger studies with randomized data are needed to assess whether it has any superiority over other existing techniques.}, } @article {pmid30567909, year = {2018}, author = {Shahbazi, S and Valizadeh, S and Borimnejad, L and Rahmani, A and Vaismoradi, M}, title = {Living With Moral Distress: The Perspectives and Experiences of Iranian Nurse Preceptors.}, journal = {Research and theory for nursing practice}, volume = {32}, number = {4}, pages = {355-369}, doi = {10.1891/1541-6577.32.4.355}, pmid = {30567909}, issn = {1541-6577}, mesh = {Faculty, Nursing/*psychology ; Humans ; Interviews as Topic ; Iran ; *Moral Obligations ; *Nurse's Role ; *Preceptorship ; }, abstract = {Background and Purpose: Preceptors play a key role in the transition experience of new nurses. Preceptorship is a stressful role and is influenced by contextual factors. There is a lack of sufficient understandings of the perspectives and lived experiences of Iranian nurse preceptors of preceptorship. The aim of this study was to explore the perspective and lived experiences of Iranian nurse preceptors of preceptorship. Methods: A qualitative design using a hermeneutic phenomenological approach was used. Six Iranian nurse preceptors were chosen using a purposeful sampling method from a large paediatric teaching hospital in an urban area of Iran. Data was collected using in-depth semi-structured interviews and was analysed using the Diekelmann et al.'s method of hermeneutic phenomenological analysis. Results: The data analysis resulted in the development of a constitutive pattern of 'living with moral distress', which was constituted of two major themes: 'asking for and being unable' and 'the experience of conflict'. Implications for Practice: The findings of this study can improve nurses' understandings of the preceptor's role and associated factors influencing the implementation of the preceptorship programme. 'Moral distress' caused by the preceptor role can influence nurse preceptors' mental health and also the patient care outcomes. More studies are required to explore this phenomenon in different contexts and cultures and design strategies for reducing the burden of taking this role on nurse preceptors. Also, policies are needed for developing a formal preceptor support system to help preceptors take this stressful and demanding role in healthcare settings.}, } @article {pmid30567374, year = {2018}, author = {Ryu, J and Lee, H and Kim, H and Won, D}, title = {Secure and Efficient Three-Factor Protocol for Wireless Sensor Networks.}, journal = {Sensors (Basel, Switzerland)}, volume = {18}, number = {12}, pages = {}, pmid = {30567374}, issn = {1424-8220}, mesh = {Algorithms ; *Computer Communication Networks ; Computer Security ; *Wireless Technology ; }, abstract = {Wireless sensor networks are widely used in many applications such as environmental monitoring, health care, smart grid and surveillance. Many security protocols have been proposed and intensively studied due to the inherent nature of wireless networks. In particular, Wu et al. proposed a promising authentication scheme which is sufficiently robust against various attacks. However, according to our analysis, Wu et al.'s scheme has two serious security weaknesses against malicious outsiders. First, their scheme can lead to user impersonation attacks. Second, user anonymity is not preserved in their scheme. In this paper, we present these vulnerabilities of Wu et al.'s scheme in detail. We also propose a new scheme to complement their weaknesses. We improve and speed up the vulnerability of the Wu et al. scheme. Security analysis is analyzed by Proverif and informal analysis is performed for various attacks.}, } @article {pmid30564900, year = {2018}, author = {Chen, R and Peng, D}, title = {Analysis and Improvement of a Mutual Authentication Scheme for Wireless Body Area Networks.}, journal = {Journal of medical systems}, volume = {43}, number = {2}, pages = {19}, pmid = {30564900}, issn = {1573-689X}, support = {U1435213,61172180//National Natural Science Foundation of China (CN)/ ; 2016-GH02-00048-HZ,2015-GH02-00041- HZ//Chengdu International Cooperation Project/ ; 18ZB0485//General Project of Education Department in Sichan/ ; }, mesh = {Computer Security/*standards ; Confidentiality ; Humans ; Monitoring, Ambulatory/*methods/standards ; Remote Sensing Technology/*methods/standards ; Telemedicine/*methods/standards ; *Wireless Technology ; }, abstract = {An increase in aging population and the consequent chronic diseases pose not only serious effects to the economy but also a heavy burden to the medical system. Wireless body area networks (WBANs) provide a simple and low-cost strategy for health monitoring and telemedicine of the elderly. Many authentication schemes based on WBAN have been presented to address the sensitivity and privacy of collected data and the open characteristic of wireless networks. Wu et al. recently presented an efficient anonymous authentication scheme for WBANs, in which a one-side bilinear pairing methodology was applied to reduce the burden on the WBAN client side. However, we demonstrate that their scheme suffers from client impersonation attacks and that the adversary can easily forge a legal client to access the network service. In this paper, we analyze the limitations of Wu et al.'s scheme and design a novel mutual authentication scheme for WBANs that adopt asymmetric bilinear pairing to enhance security. Results of security and performance analyses reveal that the new scheme offers more effective security, better performance, and higher efficiency than Wu et al.'s scheme. We also provide a formal security proof of the protocol by using BAN authentication logic.}, } @article {pmid30559959, year = {2018}, author = {Westheimer, G}, title = {Hering Hermeneutics: Supplement to Translation and Commentary of Hering (1899) by Strasburger et al.}, journal = {i-Perception}, volume = {9}, number = {6}, pages = {2041669518815921}, pmid = {30559959}, issn = {2041-6695}, abstract = {Strasburger et al.'s welcome translation of Hering's seminal paper, and reminder of what Hering actually said about eye movements and spatial averaging in vernier acuity, is supplemented by references to further trends on how the subject has evolved to the present state of knowledge.}, } @article {pmid30558612, year = {2018}, author = {, and Ogbe, E and Van Braeckel, D and Temmerman, M and Larsson, EC and Keygnaert, I and De Los Reyes Aragón, W and Cheng, F and Lazdane, G and Cooper, D and Shamu, S and Gichangi, P and Dias, S and Barrett, H and Nobels, A and Pei, K and Galle, A and Esho, T and Knight, L and Tabana, H and Degomme, O}, title = {Opportunities for linking research to policy: lessons learned from implementation research in sexual and reproductive health within the ANSER network.}, journal = {Health research policy and systems}, volume = {16}, number = {1}, pages = {123}, pmid = {30558612}, issn = {1478-4505}, mesh = {Administrative Personnel ; *Delivery of Health Care ; *Health Policy ; *Health Services Research ; Humans ; *Policy Making ; *Reproductive Health ; Reproductive Rights ; Research Personnel ; *Sexual Health ; Stakeholder Participation ; *Translational Research, Biomedical ; }, abstract = {BACKGROUND: The uptake of findings from sexual and reproductive health and rights research into policy-making remains a complex and non-linear process. Different models of research utilisation and guidelines to maximise this in policy-making exist, however, challenges still remain for researchers to improve uptake of their research findings and for policy-makers to use research evidence in their work.

METHODS: A participatory workshop with researchers was organised in November 2017 by the Academic Network for Sexual and Reproductive Health and Rights Policy (ANSER) to address this gap. ANSER is a consortium of experienced researchers, some of whom have policy-making experience, working on sexual and reproductive health and rights issues across 16 countries and 5 continents. The experiential learning cycle was used to guide the workshop discussions based on case studies and to encourage participants to focus on key lessons learned. Workshop findings were thematically analysed using specific stages from Hanney et al.'s (Health Res Policy Syst 1:2, 2003) framework on the place of policy-making in the stages of assessment of research utilisation and outcomes.

RESULTS: The workshop identified key strategies for translating research into policy, including joint agenda-setting between researchers and policy-makers, as well as building trust and partnerships with different stakeholders. These were linked to stages within Hanney et al.'s framework as opportunities for engaging with policy-makers to ensure uptake of research findings.

CONCLUSION: The engagement of stakeholders during the research development and implementation phases, especially at strategic moments, has a positive impact on uptake of research findings. The strategies and stages described in this paper can be applied to improve utilisation of research findings into policy development and implementation globally.}, } @article {pmid30550332, year = {2018}, author = {Kuhlmann, BG and Undorf, M}, title = {Is all metamemory monitoring spared from aging? A dual-process examination.}, journal = {Psychology and aging}, volume = {33}, number = {8}, pages = {1152-1167}, doi = {10.1037/pag0000318}, pmid = {30550332}, issn = {1939-1498}, support = {//Deutsche Forschungsgemeinschaft/ ; //state of Baden-Württemberg/ ; }, mesh = {Adolescent ; Adult ; Aging/*physiology ; Female ; Humans ; Learning ; Male ; Mental Recall/*physiology ; Metacognition/*physiology ; Young Adult ; }, abstract = {Although recollection-based memory declines with age, relative metamemory monitoring is reported to be spared from aging. Based on a dual-process perspective on memory, we tested whether it is specifically the monitoring of automatic influences of memory (familiarity), but not of recollection, that is spared. In Experiment 1, we used the process-dissociation procedure (PDP) task from Undorf, Böhm, and Cüpper (2016) requiring modality-based exclusions and found older (61-83 years) adults' judgments of learning (JOLs) to predict both recollection and familiarity estimates. Comparisons to Undorf et al.'s younger-adult (18-34 years) data revealed fully spared familiarity monitoring but provided some evidence for impaired recollection monitoring, especially after study-test experience. We replicated aging-spared familiarity monitoring but impaired recollection monitoring in a second experiment, comparing the predictive value of younger (18-30 years) and older (60-87 years) adults' JOLs on a different PDP task that required recollection of the words' spatial positions. Furthermore, Experiment 2 found no evidence that mediator-based strategy use improved recollection monitoring in either age group, albeit significantly improving recollection. Taken together, the results suggest that not all metamemory monitoring is spared from aging. Instead, metamemory monitoring mirrored older adults' specific deficit in recollection whereas familiarity monitoring was fully spared. (PsycINFO Database Record (c) 2018 APA, all rights reserved).}, } @article {pmid30548725, year = {2019}, author = {Gilligan, KA and Hodgkiss, A and Thomas, MSC and Farran, EK}, title = {The developmental relations between spatial cognition and mathematics in primary school children.}, journal = {Developmental science}, volume = {22}, number = {4}, pages = {e12786}, doi = {10.1111/desc.12786}, pmid = {30548725}, issn = {1467-7687}, mesh = {Aptitude ; Child ; Cognition/*physiology ; Female ; Humans ; Male ; *Mathematics ; Schools ; Spatial Navigation/*physiology ; Vocabulary ; }, abstract = {Spatial thinking is an important predictor of mathematics. However, existing data do not determine whether all spatial sub-domains are equally important for mathematics outcomes nor whether mathematics-spatial associations vary through development. This study addresses these questions by exploring the developmental relations between mathematics and spatial skills in children aged 6-10 years (N = 155). We extend previous findings by assessing and comparing performance across Uttal et al.'s (2013), four spatial sub-domains. Overall spatial skills explained 5%-14% of the variation across three mathematics performance measures (standardized mathematics skills, approximate number sense and number line estimation skills), beyond other known predictors of mathematics including vocabulary and gender. Spatial scaling (extrinsic-static sub-domain) was a significant predictor of all mathematics outcomes, across all ages, highlighting its importance for mathematics in middle childhood. Other spatial sub-domains were differentially associated with mathematics in a task- and age-dependent manner. Mental rotation (intrinsic-dynamic skills) was a significant predictor of mathematics at 6 and 7 years only which suggests that at approximately 8 years of age there is a transition period regarding the spatial skills that are important for mathematics. Taken together, the results support the investigation of spatial training, particularly targeting spatial scaling, as a means of improving both spatial and mathematical thinking.}, } @article {pmid30543820, year = {2019}, author = {DeBruine, LM and Hahn, AC and Jones, BC}, title = {Does the interaction between partnership status and average progesterone level predict women's preferences for facial masculinity?.}, journal = {Hormones and behavior}, volume = {107}, number = {}, pages = {80-82}, doi = {10.1016/j.yhbeh.2018.12.004}, pmid = {30543820}, issn = {1095-6867}, mesh = {Adolescent ; Adult ; Choice Behavior/*physiology ; *Face/anatomy & histology ; Female ; Humans ; *Interpersonal Relations ; Male ; *Masculinity ; Photic Stimulation ; Progesterone/*analysis/metabolism ; Saliva/chemistry/metabolism ; Sexual Partners/*psychology ; Social Desirability ; Young Adult ; }, abstract = {Many studies have attempted to identify biological factors that reliably predict individual differences in women's preferences for masculine male faces. Marcinkowska et al. (2018, Hormones & Behavior) recently reported that women's (N = 102) preferences for facial masculinity were predicted by the interaction between their relationship status (partnered versus unpartnered) and average progesterone level. Because previous findings for between-women differences in masculinity preferences have often not replicated well, we attempted to replicate Marcinkowska et al.'s result in an open data set from another recent study that had not tested this hypothesis (Jones et al., 2018, Psychological Science). In this sample of 316 women, we found that facial masculinity preferences were predicted by the interaction between women's relationship status and average progesterone level, consistent with Marcinkowska et al.'s results (data and analysis code are available at https://osf.io/q9szc). Together, these findings suggest that the combined effects of relationship status and average progesterone level may predict facial masculinity preferences relatively reliably.}, } @article {pmid30540746, year = {2018}, author = {Yang, X and Wang, J and Ma, T and Li, Y and Wang, C}, title = {A short certificateless aggregate signature against coalition attacks.}, journal = {PloS one}, volume = {13}, number = {12}, pages = {e0205453}, pmid = {30540746}, issn = {1932-6203}, mesh = {*Computer Security ; *Models, Theoretical ; }, abstract = {Certificateless aggregate signature (CLAS) is a crucial cryptosystem. It can not only compress multiple signatures into a short signature, but also ensure the validity of each signature participating in the aggregation by verifying the validity of an resulting aggregate signature. Therefore, a secure and efficient CLAS scheme is very useful for resource-constrained environments because it greatly reduces the overall length of the signature and the verifier's computational overhead. Cheng et al. presented an efficient CLAS scheme and proved its security in the random oracle model. However, we find that their scheme has security flaws. In this paper, we demonstrate that Cheng et al.'s CLAS scheme is vulnerable to coalition attacks from internal signers. To overcome these attacks, we present an improved CLAS scheme and prove that it is existentially unforgeable under the computational Diffie-Hellman assumption. In addition, our CLAS scheme can not only resist coalition attacks but also generate a very short aggregate signature. The performance analysis results show that our improved CLAS scheme is lower than the related CLAS schemes in terms of communication overhead and computation cost.}, } @article {pmid30504647, year = {2018}, author = {Kato, Y and Mizutani, T and Otsuka, N and Ezure, H and Inoue, Y}, title = {Quantitative analysis of the elastic fiber in the tunica media at the carotid bifurcation.}, journal = {Okajimas folia anatomica Japonica}, volume = {95}, number = {2}, pages = {23-27}, doi = {10.2535/ofaj.95.23}, pmid = {30504647}, issn = {1881-1736}, mesh = {Aged ; Aged, 80 and over ; Carotid Arteries/*anatomy & histology ; Elastic Tissue/*anatomy & histology ; Humans ; Microscopy/*methods ; Middle Aged ; Tunica Media/*anatomy & histology ; }, abstract = {In this study, the results of our previously reported technique of quantitative analysis by using microscopic image analysis of tissue image slices to calculate the proportion of the area of the tunica media occupied by of elastic fibers was compared with Janzen et al.'s technique at the carotid bifurcation. This particularly analyzed the area of transition between the common carotid and the internal carotid, to observe the quantitative changes in elastic fiber content. The data obtained from our quantitative analysis of elastic fibers were clearly at variance with those obtained by counting the number of elastic fibers. The amount of elastic fibers in the tunica media (the elastic fiber ratio) decreased from the proximal carotid artery (the common carotid) to the bifurcation, then peaked in the internal carotid immediately after the bifurcation before declining again.}, } @article {pmid30513045, year = {2019}, author = {Matusz, PJ and Turoman, N and Tivadar, RI and Retsa, C and Murray, MM}, title = {Brain and Cognitive Mechanisms of Top-Down Attentional Control in a Multisensory World: Benefits of Electrical Neuroimaging.}, journal = {Journal of cognitive neuroscience}, volume = {31}, number = {3}, pages = {412-430}, doi = {10.1162/jocn_a_01360}, pmid = {30513045}, issn = {1530-8898}, mesh = {Adult ; Attention/*physiology ; Brain/*physiology ; Cognition/*physiology ; Cues ; Electroencephalography ; Female ; Humans ; Male ; Neuroimaging ; Photic Stimulation ; Reaction Time/physiology ; Visual Perception/*physiology ; Young Adult ; }, abstract = {In real-world environments, information is typically multisensory, and objects are a primary unit of information processing. Object recognition and action necessitate attentional selection of task-relevant from among task-irrelevant objects. However, the brain and cognitive mechanisms governing these processes remain not well understood. Here, we demonstrate that attentional selection of visual objects is controlled by integrated top-down audiovisual object representations ("attentional templates") while revealing a new brain mechanism through which they can operate. In multistimulus (visual) arrays, attentional selection of objects in humans and animal models is traditionally quantified via "the N2pc component": spatially selective enhancements of neural processing of objects within ventral visual cortices at approximately 150-300 msec poststimulus. In our adaptation of Folk et al.'s [Folk, C. L., Remington, R. W., & Johnston, J. C. Involuntary covert orienting is contingent on attentional control settings. Journal of Experimental Psychology: Human Perception and Performance, 18, 1030-1044, 1992] spatial cueing paradigm, visual cues elicited weaker behavioral attention capture and an attenuated N2pc during audiovisual versus visual search. To provide direct evidence for the brain, and so, cognitive, mechanisms underlying top-down control in multisensory search, we analyzed global features of the electrical field at the scalp across our N2pcs. In the N2pc time window (170-270 msec), color cues elicited brain responses differing in strength and their topography. This latter finding is indicative of changes in active brain sources. Thus, in multisensory environments, attentional selection is controlled via integrated top-down object representations, and so not only by separate sensory-specific top-down feature templates (as suggested by traditional N2pc analyses). We discuss how the electrical neuroimaging approach can aid research on top-down attentional control in naturalistic, multisensory settings and on other neurocognitive functions in the growing area of real-world neuroscience.}, } @article {pmid30497336, year = {2020}, author = {Hardenbol, AX and Knols, B and Louws, M and Meulendijk, M and Askari, M}, title = {Usability aspects of medication-related decision support systems in the outpatient setting: A systematic literature review.}, journal = {Health informatics journal}, volume = {26}, number = {1}, pages = {72-87}, doi = {10.1177/1460458218813732}, pmid = {30497336}, issn = {1741-2811}, mesh = {*Decision Support Systems, Clinical/standards ; Humans ; *Medical Order Entry Systems ; Medication Errors/statistics & numerical data ; *Prescriptions/statistics & numerical data ; }, abstract = {In this study, we evaluated the usability aspects of medication-related clinical decision support systems in the outpatient setting. Articles published between 2000 and 2016 in Scopus, PubMed and EMBASE were searched and classified into three usability aspects: Effectiveness, Efficiency and Satisfaction. Using Van Welie et al.'s usability model, we categorized usability aspects in terms of usage indicators and means. Out of the 1999 articles, 24 articles met the selection criteria of which the main focus was on reducing inappropriate medication, prescription rate and prescription errors. Evidence could mainly be found for Effectiveness and showed high rates of positive results in reducing medication errors. To date, the effects of Efficiency and Satisfaction of clinical decision support systems regarding medication prescription remain understudied. Usability aspects such as memorability, learnability, adaptability, shortcuts and consistency require more attention. Studies are needed for better insight into the user model and to design a knowledge/task model for clinical decision support systems regarding medication prescription.}, } @article {pmid30486085, year = {2018}, author = {Brower, AVZ}, title = {Alternative facts: a reconsideration of putatively natural interspecific hybrid specimens in the genus Heliconius (Lepidoptera: Nymphalidae).}, journal = {Zootaxa}, volume = {4499}, number = {1}, pages = {1-87}, doi = {10.11646/zootaxa.4499.1.1}, pmid = {30486085}, issn = {1175-5334}, mesh = {Animals ; Biological Evolution ; *Butterflies ; Genome ; *Hybridization, Genetic ; }, abstract = {Mallet et al. (2007 BMC Evolutionary Biology, 7, 28) employed a database of putative interspecific hybrid specimens of the genus Heliconius to advance a hypothesis of "the species boundary as a continuum." Here, each of those specimens, as well as subsequently documented specimens, is individually reassessed regarding its phenotype, potential parentage and chain of custody in collections. Using a quantified scale of reliability, most of the specimens are interpreted differently than Mallet et al.'s identifications, and the actual number of interspecific hybrids is estimated to be much smaller than they proposed. To be specific, of 163 putative hybrid specimens examined, 11% suffered from ambiguous identity, 5% from confounding issues with their data labels, 50% were arguably intraspecific (depending upon alternative species concepts), and 22% were almost certainly reared, commercial specimens. Only eleven of the specimens meet the criteria established here to be legitimate and reliable interspecific hybrids, and all of those are between closely-related species. This result has potentially important implications for current hypotheses of frequent genomic introgression of wing pattern alleles among Heliconius clades.}, } @article {pmid30483059, year = {2018}, author = {Vandervert, L}, title = {How Prediction Based on Sequence Detection in the Cerebellum Led to the Origins of Stone Tools, Language, and Culture and, Thereby, to the Rise of Homo sapiens.}, journal = {Frontiers in cellular neuroscience}, volume = {12}, number = {}, pages = {408}, pmid = {30483059}, issn = {1662-5102}, abstract = {This article extends Leiner et al.'s watershed position that cerebellar mechanisms played prominent roles in the evolution of the manipulation and refinement of ideas and language. First it is shown how cerebellar mechanism of sequence-detection may lead to the foundational learning of a predictive working memory in the infant. Second, it is argued how this same cerebellar mechanism may have led to the adaptive selection toward the progressively predictive phonological loop in the evolution of working memory of pre-humans. Within these contexts, cerebellar sequence detection is then applied to an analysis of leading anthropologists Stout and Hecht's cerebral cortex-based explanation of the evolution of culture and language through the repetitious rigors of stone-tool knapping. It is argued that Stout and Hecht's focus on the roles of areas of the brain's cerebral cortex is seriously lacking, because it can be readily shown that cerebellar sequence detection importantly (perhaps predominantly) provides more fundamental explanations for the origins of culture and language. It is shown that the cerebellum does this in the following ways: (1) through prediction-enhancing silent speech in working memory, (2) through prediction in observational learning, and (3) through prediction leading to accuracy in stone-tool knapping. It is concluded, in agreement with Leiner et al. that the more recently proposed mechanism of cerebellar sequence-detection has played a prominent role in the evolution of culture, language, and stone-tool technology, the earmarks of Homo sapiens. It is further concluded that through these same mechanisms the cerebellum continues to play a prominent role in the relentless advancement of culture.}, } @article {pmid30478717, year = {2018}, author = {Lisboa, SN and Guedes, BS and Ribeiro, N and Sitoe, A}, title = {Biomass allometric equation and expansion factor for a mountain moist evergreen forest in Mozambique.}, journal = {Carbon balance and management}, volume = {13}, number = {1}, pages = {23}, pmid = {30478717}, issn = {1750-0680}, support = {2013//Fundo Nacional de Investigação (FNI). Moçambique/ ; }, abstract = {BACKGROUND: Worldwide, forests are an important carbon sink and thus are key to mitigate the effects of climate change. Mountain moist evergreen forests in Mozambique are threatened by agricultural expansion, uncontrolled logging, and firewood collection, thus compromising their role in carbon sequestration. There is lack of local tools for above-ground biomass (AGB) estimation of mountain moist evergreen forest, hence carbon emissions from deforestation and forest degradation are not adequately known. This study aimed to develop biomass allometric equations (BAE) and biomass expansion factor (BEF) for the estimation of total above-ground carbon stock in mountain moist evergreen forest.

METHODS: The destructive method was used, whereby 39 trees were felled and measured for diameter at breast height (DBH), total height and the commercial height. We determined the wood basic density, the total dry weight and merchantable timber volume by Smalian's formula. Six biomass allometric models were fitted using non-linear least square regression. The BEF was determined based on the relationship between bole stem dry weight and total dry weight of the tree. To estimate the mean AGB of the forest, a forest inventory was conducted using 27 temporary square plots. The applicability of Marzoli's volume equation was compared with Smalian's volume equation in order to check whether Marzoli's volume from national forest inventory can be used to predict AGB using BEF.

RESULTS: The best model was the power model with only DBH as predictor variable, which provided an estimated mean AGB of 291 ± 141 Mg ha[-1] (mean ± 95% confidence level). The mean wood basic density of sampled trees was 0.715 ± 0.182 g cm[-3]. The average BEF was of 2.05 ± 0.15 and the estimated mean AGB of 387 ± 126 Mg ha[-1]. The BAE from miombo woodland within the vicinity of the study area underestimates the AGB for all sampled trees. Chave et al.'s pantropical equation of moist forest did not fit to the Moribane Forest Reserve, while Brown's equation of moist forest had a good fit to the Moribane Forest Reserve, having generated 1.2% of bias, very close to that generated by the selected model of this study. BEF showed to be reliable when combined with stand mean volume from Marzoli's National Forestry Inventory equation.

CONCLUSION: The BAE and the BEF function developed in this study can be used to estimate the AGB of the mountain moist evergreen forests at Moribane Forest Reserve in Mozambique. However, the use of the biomass allometric model should be preferable when DBH information is available.}, } @article {pmid30478621, year = {2019}, author = {Weinstein, RA}, title = {Clarification of errors in Abbas et al.'s conflict of interest narrative review.}, journal = {Intensive care medicine}, volume = {45}, number = {1}, pages = {128-129}, pmid = {30478621}, issn = {1432-1238}, mesh = {*Conflict of Interest ; *Smoke ; }, } @article {pmid30476023, year = {2019}, author = {Bamford, P and Rogers, J}, title = {Where's the bleed? A response to Piccini et al.'s: Management of major bleeding events in patients treated with rivaroxaban vs. warfarin: results from the ROCKET AF trial.}, journal = {European heart journal}, volume = {40}, number = {19}, pages = {1567}, doi = {10.1093/eurheartj/ehy739}, pmid = {30476023}, issn = {1522-9645}, mesh = {Anticoagulants ; Hemorrhage ; Humans ; *Rivaroxaban ; *Warfarin ; }, } @article {pmid30474604, year = {2018}, author = {Sahranavard, S and Esmaeili, A and Dastjerdi, R and Salehiniya, H}, title = {The effectiveness of stress-management-based cognitive-behavioral treatments on anxiety sensitivity, positive and negative affect and hope.}, journal = {BioMedicine}, volume = {8}, number = {4}, pages = {23}, pmid = {30474604}, issn = {2211-8020}, abstract = {BACKGROUND AND OBJECTIVE: Anxiety sensitivity, positive and negative affection and hope are the important factors in promoting mental health of students. The purpose of this study was to investigate the effectiveness of stress-management-based cognitive-behavioral treatments on anxiety sensitivity, hope, positive and negative affect in female students of Medical Sciences.

MATERIALS AND METHODS: This research was a trail study with pre-test, post-test and control group. A sample of 30 subjects, were selected by available sampling and were randomly assigned using Block Randomization Method of two groups (experimental and control groups). Schneider's hope questionnaire, Watson's positive and negative affect questionnaire, Clarke and Tolgman's questionnaire, Reiss et al.'s anxiety sensitivity of the revised index questionnaire, were completed in two stages (pre-test and post-test) by all subjects. A 6-session protocol of cognitive-behavioral group treatment was performed only on the experimental group. The data were analyzed using ANOVA and MANOVA analysis of variance.

RESULTS: Two experimental and control groups with the mean 22, standard deviationl. 13, average age is 22 years. Stress-management-based cognitive-behavioral treatments were effective on the level of anxiety sensitivity and hope (p <0.016), however, it had no significant positive effect on the amount of positive and negative affect (p <0.016).

CONCLUSION: According to the results, it can be concluded that cognitive-behavioral treatments are effective on anxiety sensitivity and hope. Therefore, stress-management-based cognitive-behavioral training can reduce students' anxiety sensitivity and increase their hopes for coping with challenges.}, } @article {pmid30430293, year = {2019}, author = {Wo, N and Rajagopal, V and Cheung, MMH and Smolich, JJ and Mynard, JP}, title = {Assessment of single beat end-systolic elastance methods for quantifying ventricular contractility.}, journal = {Heart and vessels}, volume = {34}, number = {4}, pages = {716-723}, pmid = {30430293}, issn = {1615-2573}, mesh = {Animals ; Heart Rate/*physiology ; Male ; Models, Animal ; Myocardial Contraction/*physiology ; Sheep ; Stroke Volume/*physiology ; Ventricular Function, Left/*physiology ; }, abstract = {Multi-beat end-systolic elastance (EMB) is considered a gold-standard index of ventricular contractility. However, it is difficult to measure clinically due to the need for transient manipulation of ventricular preload or afterload. We compared the performance of 5 'single-beat' methods that do not require loading interventions, for estimating the equivalent of EMB. In 7 sheep instrumented with a micromanometer/conductance catheter, single-beat methods were compared with EMB, obtained after transiently decreasing preload or increasing afterload under a broad range of heart rates and inotropic conditions. The single-beat elastance (ESB) method described by Shishido et al. (Circulation 102(16):1983-1989, 2000) had the highest correlation (R = 0.69, y = 0.52x + 0.43) with EMB, although the absolute accuracy was poor. Interestingly, for all methods tested, a higher correlation was observed when EMB was obtained with an afterload increase (R = 0.47 - 0.78) rather than a preload reduction (R = 0.07-0.57). Within-animal regression coefficients were higher than those obtained from pooled data, with excellent within-animal correlation observed for Shishido et al. method (0.73 ≤ R ≤ 0.96) when using afterload increase as the loading intervention. We conclude that (1) current methods perform better when using an afterload increase to obtain reference EMB, (2) intra-individual ESB comparisons may be more reliable than inter-individual comparisons and (3) Shishido et al.'s method demonstrated the strongest correlation with EMB. Current ESB methods have limited and variable accuracy, but may hold promise for tracking relative changes in ventricular contractility in individuals.}, } @article {pmid30430072, year = {2018}, author = {Manikya, S and Sureka, V and Prasanna, MD and Ealla, K and Reddy, S and Bindu, PS}, title = {Comparison of Cheiloscopy and Rugoscopy in Karnataka, Kerala, and Manipuri Population.}, journal = {Journal of International Society of Preventive & Community Dentistry}, volume = {8}, number = {5}, pages = {439-445}, pmid = {30430072}, issn = {2231-0762}, abstract = {AIMS AND OBJECTIVES: The aim of the study was to evaluate and compare lip prints and palatal rugae pattern in Kerala, Karnataka, and Manipuri population.

MATERIALS AND METHODS: The study involved 180 individuals (60 each from Karnataka, Kerala, and Manipuri population). Lipstick was used to record lip prints, which were visualized by magnifying lens. Palatal rugae were recorded on maxillary casts of all subjects and analyzed following Kapali S et al.' s classification. Statistical Package for the Social Sciences version 20 for Windows software was used for analysis.

RESULTS: Among the study population, most frequent lip print pattern was Type 3 and least was Type 1'. When patterns were compared between groups, Type 3 was the most common in Manipuri and Kerala and Type 3 in Karnataka groups. In the entire population, males showed Type 3 and females showed Type 1. On analysis of overall rugae wavy, forward and divergence patterns were predominant. On comparison of gender, males demonstrated greater number of wavy and perpendicular rugae, and females had curved, straight, forward, and backward.

CONCLUSION: Both cheiloscopy and rugoscopy have the prospective to recognize an individual. Cheiloscopy is more reliable than rugoscopy in making out the group and gender of an individual.}, } @article {pmid30414708, year = {2018}, author = {Halilah, T and Khdairi, N and Jost-Brinkmann, PG and Bartzela, T}, title = {Age estimation in 5-16-year-old children by measurement of open apices: North German formula.}, journal = {Forensic science international}, volume = {293}, number = {}, pages = {103.e1-103.e8}, doi = {10.1016/j.forsciint.2018.09.022}, pmid = {30414708}, issn = {1872-6283}, mesh = {Adolescent ; Age Determination by Teeth/*methods ; Child ; Child, Preschool ; Female ; Germany ; Humans ; Male ; Radiography, Panoramic ; Regression Analysis ; Retrospective Studies ; Tooth Apex/*diagnostic imaging/*growth & development ; }, abstract = {The aims of this study were to test the accuracy of Cameriere et al.'s European formula on a sample of North German children based on dental age (DA) for chronological age (CA) assessment and to adapt the formula used, in case of regional peculiarities of this group of children. Orthopantomograms of 1000 children (444 males and 556 females) aged 5-16years were used. The roots of seven left mandibular teeth were evaluated. The number of teeth with complete root development (N zero (0)) was counted. Teeth with incomplete root development were examined and the distance between the inner sides of the open apex was measured and normalized by dividing it by the tooth length to avoid error due to magnification. Cameriere et al.'s European formula underestimated the mean CA of boys by 0.56±1.04years and of girls by -0.32±0.96. The results of the regression analysis showed that sex (g), the sum of normalized open apices (s), number of teeth with closed apices (N0) and the first-order interaction between the normalized apex width of the canine (x3) and N0 contributed significantly to the fit. All previously mentioned factors were included in the regression model, yielding to the following formula: DA=9.829+0.632 N0-1.037s+0.686g-1.582N0×x3, where g is a variable: 1 for males and 0 for females. The adapted formula explained 84.1% of the total deviance, with a median age of 0.070 years and 1.185 years interquartile range, (IQR).}, } @article {pmid30414277, year = {2019}, author = {Franz, AM and Seitel, A and Cheray, D and Maier-Hein, L}, title = {Polhemus EM tracked Micro Sensor for CT-guided interventions.}, journal = {Medical physics}, volume = {46}, number = {1}, pages = {15-24}, doi = {10.1002/mp.13280}, pmid = {30414277}, issn = {2473-4209}, support = {//European Research Council/ ; //German Aerospace Center (DLR)/ ; }, mesh = {*Electromagnetic Fields ; Laboratories ; Microtechnology/*instrumentation ; Phantoms, Imaging ; *Tomography, X-Ray Computed ; }, abstract = {PURPOSE: Electromagnetic (EM) tracking is a key technology in image-guided therapy. A new EM Micro Sensor was presented by Polhemus Inc.; it is the first to enable localization of medical instruments through their trackers. Different field generators (FGs) are available by Polhemus, one being almost as small as a sugar cube. As accuracy and robustness of tracking are known challenges to using EM trackers in clinical environments, the goal of this study was a standardized assessment of the Micro Sensor in both a laboratory (lab) and a computed tomography (CT) environment.

METHODS: The Micro Sensor was assessed by means of Hummel et al.'s standardized protocol; it was assessed in conjunction with a Polhemus Liberty tracker and three FGs - with edge lengths of 1 (TX1), 2 (TX2), and 4 (TX4) inches. Precision as well as positional and rotational accuracy were determined in a lab and a CT suite. Distortions by four different metallic cylinders and tracking of two typical medical instruments - a hypodermic needle and a flexible endoscope - were also tested.

RESULTS: A jitter of 0.02 mm or less was found for all FGs in the different environments, except for the TX2 FG for which no valid data could be obtained in the CT. Errors of 5 cm distance measurements were 0.6 mm or less for all FGs in the lab. While the distance errors of the TX1 FG were only slightly increased up to 1.6 mm in the CT, those of the TX4 FG were found to be up to around 10% of the measured distance (5.4 mm on average). The mean orientation error was found to be 0.9[°] /0.5[°] /0.1[°] for the TX4/TX2/TX1 FG in the lab. In the CT environment, rotation errors were in the same range: less than 1.2[°] /0.1[°] for the TX4/TX1 FG. Deviation under the presence of metallic cylinders stayed below 1 mm in most cases. Precision and orientational accuracy do not seem to be affected by instrument tracking and stayed in the same range as for the other measurements whereas distance errors were slightly increased up to 1.7 mm.

CONCLUSION: This study shows that accurate tracking of medical instruments is possible with the new Micro Sensor; it demonstrated a jitter of 0.01 mm or less, position errors below 2 mm, and rotation errors of less than 0.3[°] . As with other EM trackers, errors increase when large tracking volumes with ranges of up to 50 cm are required in clinical environments. For smaller tracking volumes with ranges of up to 15 cm, a high accuracy and robustness was found. This is interesting especially for the TX1 FG which can easily be placed in close vicinity to the region of interest.}, } @article {pmid30412915, year = {2019}, author = {Goto, R and Mori, T}, title = {Comparison of Equity Preferences for Life Expectancy Gains: A Discrete Choice Experiment Among the Japanese and Korean General Public.}, journal = {Value in health regional issues}, volume = {18}, number = {}, pages = {8-13}, doi = {10.1016/j.vhri.2018.05.004}, pmid = {30412915}, issn = {2212-1102}, mesh = {Adult ; Asian People/ethnology/psychology/statistics & numerical data ; Female ; Humans ; Japan ; Life Expectancy/*ethnology ; Male ; Middle Aged ; National Health Programs/*standards/statistics & numerical data ; *Public Opinion ; Quality-Adjusted Life Years ; Republic of Korea ; Surveys and Questionnaires ; }, abstract = {BACKGROUND: Setting priorities for limited public resources has become a topic of heated discussion the world over. Assigning different weights for the health gains of different population groups allows for equity considerations in cost-effectiveness analysis. However, only a few empirical works have elicited the preferences of the general public.

OBJECTIVE: To compare the equity preferemce assigned by Japanese and Koreans.

METHODS: We conducted a Web-based survey in March 2013, including a discrete choice experiment, to elicit the equity preferences of the general public for the life expectancy gains of different population groups. We selected attributes and designed the experiment following Norman et al.'s study (Norman R, Hall J, Street D, Viney R. Efficiency and equity: a stated preference approach. Health Econ 2013;22:568-81). Accordingly, we analyzed preference for sex, smoking status, lifestyle, caring status, income, and age.

RESULTS: The Japanese assigned a higher preference for males (P < 0.001), nonsmokers (P < 0.001), those with lower income (P < 0.001), and carers (P < 0 .001), and they assigned a lower preference for those with a life expectancy of 60 years (P = 0.002) and 75-year-olds (P < 0.001). Koreans have the same patterns of preference for lower income (P < 0.001), caring (P < 0.001), and smoking status (P = 0.026). However, they prefer both sexes (P = 0.331) and different age groups equally. In both countries, respondents tend to prefer groups with characteristics similar to their own.

CONCLUSIONS: People from the two Asian developed countries, with universal health insurance, show different equity preferences. These may reflect the variations in cultural background and coverage of health care services.}, } @article {pmid30411203, year = {2018}, author = {Wilson, MR and Wasserman, M and Jadavji, T and Postma, M and Breton, MC and Peloquin, F and Earnshaw, SR and McDade, C and Sings, HL and Farkouh, R}, title = {Response to McGirr et al.'s Comment on "Clinical and Economic Impact of a Potential Switch from 13-Valent to 10-Valent Pneumococcal Conjugate Infant Vaccination in Canada".}, journal = {Infectious diseases and therapy}, volume = {7}, number = {4}, pages = {539-543}, pmid = {30411203}, issn = {2193-8229}, } @article {pmid30408866, year = {2018}, author = {Nayebare, SR and Aburizaiza, OS and Siddique, A and Carpenter, DO and Hussain, MM and Zeb, J and Aburiziza, AJ and Khwaja, HA}, title = {Ambient air quality in the holy city of Makkah: A source apportionment with elemental enrichment factors (EFs) and factor analysis (PMF).}, journal = {Environmental pollution (Barking, Essex : 1987)}, volume = {243}, number = {Pt B}, pages = {1791-1801}, doi = {10.1016/j.envpol.2018.09.086}, pmid = {30408866}, issn = {1873-6424}, mesh = {Air Pollutants/*analysis ; Air Pollution/*analysis ; Coal/analysis ; Dust/*analysis ; *Environmental Monitoring ; Factor Analysis, Statistical ; Humans ; Industry ; Ions/analysis ; Saudi Arabia ; Seasons ; Soil/chemistry ; Soot/*analysis ; Trace Elements/analysis ; Vehicle Emissions/*analysis ; Wind ; }, abstract = {Air pollution remains a major global public health and environmental issue. We assessed the levels of PM2.5 and delineated the major sources in Makkah, Saudi Arabia. Fine particulate matter (PM2.5) sampling was performed from February 26, 2014-January 27, 2015 in four cycles/seasons. Samples were analyzed for black carbon (BC) and trace elements (TEs). PM2.5 source apportionment was performed by computing enrichment factors (EFs) and positive matrix factorization (PMF). Backward-in time trajectories were used to assess the long-range transport. Significant seasonal variations in PM2.5 were observed, Spring: 113 ± 67.1, Summer: 88.3 ± 36.4, Fall: 67.8 ± 24, and Winter: 67.6 ± 36.9 μg m[-3]. The 24-h PM2.5 exceeded the WHO (25 μg m[-3]) and Saudi Arabia's (35 μg m[-3]) guidelines, with an air quality index (AQI) of "unhealthy to hazardous" to human health. Most delta-C computations were below zero, indicating minor contributions from bio-mass burning. TEs were primarily Si, Ca, Fe, Al, S, K and Mg, suggesting major contributions from soil (Si, Ca, Fe, Al, Mg), and industrial and vehicular emissions (S, Ca, Al, Fe, K). EF defined two broad categories of TEs as: anthropogenic (Cu, Zn, Eu, Cl, Pb, S, Br and Lu), and earth-crust derived (Al, Si, Na, Mg, Rb, K, Zr, Ti, Fe, Mn, Sr, Y, Cr, Ga, Ca, Ni and Ce). Notably, all the anthropogenic TEs can be linked to industrial and vehicular emissions. PMF analysis defined four major sources as: vehicular emissions, 30.1%; industrial-mixed dust, 28.9%; soil/earth-crust, 24.7%; and fossil-fuels/oil combustion, 16.3%. Plots of wind trajectories indicated wind direction and regional transport as major influences on air pollution levels in Makkah. In collusion, anthropogenic emissions contributed >75% of the observed air pollution in Makkah. Developing strategies for reducing anthropogenic emissions are paramount to controlling particulate air pollution in this region.}, } @article {pmid30404765, year = {2019}, author = {Bello-Perez, LA and Agama-Acevedo, E and Garcia-Valle, DE and Alvarez-Ramirez, J}, title = {A multiscale kinetics model for the analysis of starch amylolysis.}, journal = {International journal of biological macromolecules}, volume = {122}, number = {}, pages = {405-409}, doi = {10.1016/j.ijbiomac.2018.10.161}, pmid = {30404765}, issn = {1879-0003}, mesh = {Digestion ; Hydrolysis ; Kinetics ; *Models, Chemical ; Starch/*chemistry/metabolism ; }, abstract = {Simple exponential decaying functions are commonly used for fitting the kinetics of starch digested by amylolytic enzymes. A common assumption is that a sole exponential function can account for the kinetics of the whole digestible starch. Recent studies using logarithm-of-slope (LOS) plots showed that digestion kinetics can exhibit multi-scale behavior, an effect reflecting starch fractions with different digestion characteristics. This work proposed an extension of the widely used Goñi et al.'s model to account for two starch fractions; one fraction linked with fast digestion rate and other with slow digestion rates. The fitting of experimental data was carried out by solving numerically a nonlinear least-squares problem. The estimated parameters have a straightforward interpretation in terms of reaction rates and digestible/resistant starch fractions. Two experimental examples were used for illustrating the performance of the multi-exponential function.}, } @article {pmid30404579, year = {2018}, author = {Tan, M and He, FJ and MacGregor, GA}, title = {Salt and cardiovascular disease in PURE: A large sample size cannot make up for erroneous estimations.}, journal = {Journal of the renin-angiotensin-aldosterone system : JRAAS}, volume = {19}, number = {4}, pages = {1470320318810015}, pmid = {30404579}, issn = {1752-8976}, support = {16/136/77/DH_/Department of Health/United Kingdom ; MR/J015903/1/MRC_/Medical Research Council/United Kingdom ; MR/P012590/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Blood Pressure/drug effects ; Cardiovascular Diseases/*epidemiology/*etiology/mortality/urine ; Humans ; Myocardial Ischemia/etiology/physiopathology/urine ; Prospective Studies ; Sample Size ; Sodium/urine ; Sodium Chloride, Dietary/*adverse effects ; Stroke/etiology/physiopathology/urine ; }, abstract = {The latest Prospective Urban Rural Epidemiology (PURE) study claims that salt reduction should be confined to settings where its intake exceeds 12.7 g/day and that eating less than 11.1 g/day of salt could increase cardiovascular risk. More specifically, Mente et al. suggested that (a) salt intake was positively associated with stroke only when it exceeded 12.7 g/day, (b) salt intake was inversely associated with myocardial infarction and total mortality, and (c) these associations were largely independent of blood pressure. These provocative findings challenge the robust evidence on the role of salt reduction in the prevention of cardiovascular disease and call into question the World Health Organization's global recommendation to reduce salt intake to less than 5 g/day. However, Mente et al.'s re-analysis of the PURE data has several severe methodological problems, including erroneous estimations of salt intake from a single spot urine using the problematic Kawasaki formula. As such, these implausible results cannot be used to refute the strong evidence supporting the benefits of salt reduction for the general population worldwide.}, } @article {pmid30387740, year = {2020}, author = {Chen, ZZ and Harada, Y and Nakamura, Y and Wang, L}, title = {Faster Exact Computation of rSPR Distance via Better Approximation.}, journal = {IEEE/ACM transactions on computational biology and bioinformatics}, volume = {17}, number = {3}, pages = {916-929}, doi = {10.1109/TCBB.2018.2878731}, pmid = {30387740}, issn = {1557-9964}, mesh = {*Phylogeny ; *Computational Biology/methods ; *Algorithms ; *Software ; Models, Genetic ; }, abstract = {Due to hybridization events in evolution, studying two different genes of a set of species may yield two related but different phylogenetic trees for the set of species. In this case, we want to measure the dissimilarity of the two trees. The rooted subtree prune and regraft (rSPR) distance of the two trees has been used for this purpose. The problem of computing the rSPR distance of two given trees has many applications but is NP-hard. Accordingly, a number of programs have been developed for solving the problem either exactly or approximately. In this paper, we develop two new programs, one of which solves the problem exactly and outperforms the previous best (namely, Whidden et al.'s rSPR-v1.3.0) significantly, while the other solves the problem approximately and outputs significantly better lower and upper bounds on the rSPR distance of the two given trees than the previous best due to Schalekamp et al. Our programs can be downloaded at http://rnc.r.dendai.ac.jp/rspr.html.}, } @article {pmid30380595, year = {2018}, author = {Aghili, SF and Mala, H and Peris-Lopez, P}, title = {Securing Heterogeneous Wireless Sensor Networks: Breaking and Fixing a Three-Factor Authentication Protocol.}, journal = {Sensors (Basel, Switzerland)}, volume = {18}, number = {11}, pages = {}, pmid = {30380595}, issn = {1424-8220}, support = {TIN2016-79095-C2-2-R//Ministerio de Economía y Competitividad/ ; S2013/ICE-3095//CAM/ ; }, abstract = {Heterogeneous wireless sensor networks (HWSNs) are employed in many real-time applications, such as Internet of sensors (IoS), Internet of vehicles (IoV), healthcare monitoring, and so on. As wireless sensor nodes have constrained computing, storage and communication capabilities, designing energy-efficient authentication protocols is a very important issue in wireless sensor network security. Recently, Amin et al. presented an untraceable and anonymous three-factor authentication (3FA) scheme for HWSNs and argued that their protocol is efficient and can withstand the common security threats in this sort of networks. In this article, we show how their protocol is not immune to user impersonation, de-synchronization and traceability attacks. In addition, an adversary can disclose session key under the typical assumption that sensors are not tamper-resistant. To overcome these drawbacks, we improve the Amin et al.'s protocol. First, we informally show that our improved scheme is secure against the most common attacks in HWSNs in which the attacks against Amin et al.'s protocol are part of them. Moreover, we verify formally our proposed protocol using the BAN logic. Compared with the Amin et al.'s scheme, the proposed protocol is both more efficient and more secure to be employed which renders the proposal suitable for HWSN networks.}, } @article {pmid30375023, year = {2018}, author = {Aryawibawa, IN and Ambridge, B}, title = {Is Syntax Semantically Constrained? Evidence From a Grammaticality Judgment Study of Indonesian.}, journal = {Cognitive science}, volume = {42}, number = {8}, pages = {3135-3148}, doi = {10.1111/cogs.12697}, pmid = {30375023}, issn = {1551-6709}, mesh = {Adult ; Humans ; Judgment ; *Language ; Linguistics ; Psycholinguistics ; *Semantics ; }, abstract = {A central debate in the cognitive sciences surrounds the nature of adult speakers' linguistic representations: Are they purely syntactic (a traditional and widely held view; e.g., Branigan & Pickering,), or are they semantically structured? A recent study (Ambridge, Bidgood, Pine, Rowland, & Freudenthal,) found support for the latter view, showing that adults' acceptability judgments of passive sentences were significantly predicted by independent semantic "affectedness" ratings designed to capture the putative semantics of the construction (e.g., Bob was pushed by Wendy is rated as more acceptable than Bob was liked by Wendy, as Bob is more affected in the former). However, because English lacks a separate topicalization construction which provides an alternative means of highlighting the patient (e.g., BOB, Wendy kicked), these findings have a possible alternative explanation: that highly affected entities are more likely to be topicalized, rather than passivized per se. Here we show that, in fact, Ambridge et al.'s () finding replicates in Indonesian, a language with a topicalization construction. The present study therefore provides particularly compelling evidence that grammatical representations have semantic structure.}, } @article {pmid30363794, year = {2018}, author = {Petursdottir, AI and Carr, JE}, title = {Applying the Taxonomy of Validity Threats from Mainstream Research Design to Single-Case Experiments in Applied Behavior Analysis.}, journal = {Behavior analysis in practice}, volume = {11}, number = {3}, pages = {228-240}, pmid = {30363794}, issn = {1998-1929}, abstract = {Mainstream research design in the social and behavioral sciences has often been conceptualized using a taxonomy of threats to experimental validity first articulated by Campbell and his colleagues (Campbell & Stanley, 1966; Cook & Campbell, 1979). The most recent update of this framework was published by Shadish, Cook, and Campbell (2002), in which the authors describe different types of validity and numerous threats to each primarily in terms of group-design experiments. In the present article, we apply Shadish et al.'s analysis of threats to internal, external, statistical conclusion, and construct validity to single-case experimental research as it is typically conducted in applied behavior analysis. In doing so, we hope to provide researchers and educators in the field with a translation of the validity-threats taxonomy into terms and considerations relevant to the design and interpretation of applied behavior-analytic research for the purposes of more careful research design and the ability to communicate our designs to individuals outside of behavior analysis, using their own vocabulary.}, } @article {pmid30358474, year = {2021}, author = {Stoll, LC and Lilley, TG and Block, R}, title = {The Effects of Gender-Blind Sexism on Rape Myth Acceptance: Results From a Nationally Representative Study.}, journal = {Journal of interpersonal violence}, volume = {36}, number = {11-12}, pages = {5838-5859}, doi = {10.1177/0886260518807912}, pmid = {30358474}, issn = {1552-6518}, mesh = {Female ; Gender Identity ; Humans ; Male ; *Rape ; *Sex Offenses ; Sexism ; Stereotyping ; }, abstract = {This study uses a diverse sample that is nationally representative with regards to race and gender (N = 2,000) in an attempt to replicate and confirm Stoll, Lilley, and Pinter's previous finding that gender-blind sexism is correlated with rape myth acceptance. As in the original study, we hypothesized that higher scores on the Gender-Blind Sexism Inventory (GBSI) would be predictive of higher scores on Stoll et al.'s Rape Myth Acceptance Scale (RMA). Gender-blind sexism builds on previous models of contemporary sexism such as hostile and benevolent sexism, modern sexism, and neosexism. It also represents an extension of racialized social system theory that explores the ways contemporary sexism operates in an era of post-racial and post-gender politics via four frames: abstract liberalism, naturalization, cultural sexism, and minimization of sexism. Unlike in the original study, however, our sample also allowed us to control for scores on the Ambivalent Sexism Inventory (ASI), the Modern Sexism Scale (MS), and the Neosexism Scale (NS) in testing this relationship. Our analysis confirmed the hypothesis that gender-blind sexism is predictive of higher rape myth acceptance among participants. Moreover, this study indicates that the GBSI offers additional value over the ASI, MS, and NS, as it was the only index of sexism tested that revealed gender-group differences within its relationship to RMA. Compared to men, women's acceptance of rape myths was more responsive to shifts in the GBSI. We discuss the implications of our findings in terms of rape and sexual assault prevention and policy. We also provide some suggestions for how the GBSI could be used in future studies.}, } @article {pmid30358433, year = {2019}, author = {Ben-Porath, YS}, title = {Of Fallacies and Errors, New and Repeated: A Rejoinder to Butcher et al. (2018).}, journal = {Journal of personality assessment}, volume = {101}, number = {2}, pages = {129-139}, doi = {10.1080/00223891.2018.1522640}, pmid = {30358433}, issn = {1532-7752}, mesh = {Humans ; *MMPI ; Reproducibility of Results ; }, abstract = {Butcher, Hass, Greene, Nelson, Nichols, and Williams (2018) responded to my (Ben-Porath, 2018) critique of Butcher, Hass, Greene, and Nelson's (2015) analysis of Ted Kaczynski's MMPI-2-RF, purporting to find logical fallacies in my arguments and shortcomings in my interpretation of MMPI-2-RF scales. Butcher et al. (2018) repeated several previously refuted arguments and opinions, while failing to acknowledge, let alone consider, prior responses to their claims. In this rejoinder I refute (again) Butcher et al.'s assertion that empirical data raise questions about the "clinical sensitivity" of MMPI-2-RF scales, identify an extensive literature relevant to forensic use of the MMPI-2-RF that Butcher and colleagues have systematically ignored, and identify a series of logical and factual fallacies along with new and repeated errors of omission and commission in Butcher et al.'s response.}, } @article {pmid30358430, year = {2019}, author = {Bornstein, RF}, title = {From Structure to Process: On the Integration of AMPD and HiTOP.}, journal = {Journal of personality assessment}, volume = {101}, number = {4}, pages = {360-366}, doi = {10.1080/00223891.2018.1501696}, pmid = {30358430}, issn = {1532-7752}, mesh = {Diagnostic and Statistical Manual of Mental Disorders ; Humans ; *Personality ; *Personality Disorders ; Personality Inventory ; Psychopathology ; }, abstract = {In recent years the limitations of traditional categorical frameworks for conceptualizing and diagnosing psychopathology have become increasingly clear, prompting the development of dimensional models wherein psychological dysfunction is assessed on a series of continua. Two frameworks have been particularly influential: the Alternative Model for Personality Disorders (AMPD) outlined in DSM-5 (American Psychiatric Association, 2013), and the Hierarchical Taxonomy of Psychopathology (HiTOP; Kotov et al., 2017). Widiger et al.'s timely and insightful review addresses two key questions regarding AMPD and HiTOP: Do deficits in self- and interpersonal functioning (AMPD Criterion A) have incremental validity over maladaptive traits (Criterion B), and if so, should Criterion A be included in HiTOP? In this commentary I argue that to resolve these questions conclusively, studies of factor structure and construct covariation must be complemented by investigations that address three issues: (a) Are there identifiable causal links between Criterion A impairments and Criterion B traits; (b) Do salient life events, therapeutic interventions, and experimental manipulations differentially affect Criterion A and Criterion B scores; and (c) Do Criterion A and Criterion B scores predict different outcomes in laboratory, clinical, and field settings?}, } @article {pmid30357894, year = {2019}, author = {Cleland, J and Durning, SJ}, title = {Education and service: how theories can help in understanding tensions.}, journal = {Medical education}, volume = {53}, number = {1}, pages = {42-55}, doi = {10.1111/medu.13738}, pmid = {30357894}, issn = {1365-2923}, mesh = {*Clinical Competence ; Education, Medical, Graduate/*methods ; Health Personnel ; Humans ; *Internship and Residency ; *Learning ; Social Theory ; }, abstract = {OBJECTIVES: This paper reviews why tensions between service and education persist and highlights that this is an area of medical education research (MER) that, to date, lacks a robust body of theory-driven research. After carrying out a review of the literature on service-education tensions in medical education and training, we turn to consider how theory can help provide new insights into service-education tensions.

METHODS: We conducted a search of the literature on service-education tensions since 1998 to examine the use of theory in studies on this topic.

RESULTS: We identified 44 out of 603 relevant papers. Their focus fell into four broad categories: time residents spent on 'service' and 'education'; perceptions of the balance between service and education; considerations of how best to define service and education, and the impact of structural and systems changes on education/training. Of the papers reporting primary research, the dominant methodology was the bespoke survey. Rarely were the precise natures of tensions or how different factors interact to cause tensions examined in detail.

DISCUSSION: Through discussion and reflection, we then agreed on the applicability of four sociocultural theories for illuminating some examples of service-education tensions. We present four sociocultural theories: Holland's figured worlds, Kemmis et al.'s practice architectures, Lave and Wenger's situated learning and Engeström's cultural-historical activity theory (CHAT or AT). We describe each and then briefly illustrate how each theory can support new ways of thinking and potential directions for research focusing on education-service tensions.

CONCLUSIONS: The use of theory in research studies will not resolve service-education tensions. However, what theory can do is illuminate and magnify different aspects of service-education tensions, to generate new insight and knowledge that can then be used to inform future research and changes in practice.}, } @article {pmid30355607, year = {2019}, author = {Wen, J and Zhang, H and Alexander, DC and Durrleman, S and Routier, A and Rinaldi, D and Houot, M and Couratier, P and Hannequin, D and Pasquier, F and Zhang, J and Colliot, O and Le Ber, I and Bertrand, A and , }, title = {Neurite density is reduced in the presymptomatic phase of C9orf72 disease.}, journal = {Journal of neurology, neurosurgery, and psychiatry}, volume = {90}, number = {4}, pages = {387-394}, doi = {10.1136/jnnp-2018-318994}, pmid = {30355607}, issn = {1468-330X}, mesh = {Adult ; Amyotrophic Lateral Sclerosis/*diagnostic imaging/genetics ; Asymptomatic Diseases ; Brain/*diagnostic imaging ; C9orf72 Protein/*genetics ; Case-Control Studies ; Diffusion Tensor Imaging ; Family ; Female ; Frontotemporal Lobar Degeneration/*diagnostic imaging/genetics ; Heterozygote ; Humans ; Male ; Middle Aged ; Mutation ; Neurites/*pathology ; }, abstract = {OBJECTIVE: To assess the added value of neurite orientation dispersion and density imaging (NODDI) compared with conventional diffusion tensor imaging (DTI) and anatomical MRI to detect changes in presymptomatic carriers of chromosome 9 open reading frame 72 (C9orf72) mutation.

METHODS: The PREV-DEMALS (Predict to Prevent Frontotemporal Lobar Degeneration and Amyotrophic Lateral Sclerosis) study is a prospective, multicentre, observational study of first-degree relatives of individuals carrying the C9orf72 mutation. Sixty-seven participants (38 presymptomatic C9orf72 mutation carriers (C9+) and 29 non-carriers (C9-)) were included in the present cross-sectional study. Each participant underwent one single-shell, multishell diffusion MRI and three-dimensional T1-weighted MRI. Volumetric measures, DTI and NODDI metrics were calculated within regions of interest. Differences in white matter integrity, grey matter volume and free water fraction between C9+ and C9- individuals were assessed using linear mixed-effects models.

RESULTS: Compared with C9-, C9+ demonstrated white matter abnormalities in 10 tracts with neurite density index and only 5 tracts with DTI metrics. Effect size was significantly higher for the neurite density index than for DTI metrics in two tracts. No tract had a significantly higher effect size for DTI than for NODDI. For grey matter cortical analysis, free water fraction was increased in 13 regions in C9+, whereas 11 regions displayed volumetric atrophy.

CONCLUSIONS: NODDI provides higher sensitivity and greater tissue specificity compared with conventional DTI for identifying white matter abnormalities in the presymptomatic C9orf72 carriers. Our results encourage the use of neurite density as a biomarker of the preclinical phase.

TRIAL REGISTRATION NUMBER: NCT02590276.}, } @article {pmid30355178, year = {2018}, author = {Joubert, C and Davidson, PSR and Chainay, H}, title = {When Do Older Adults Show a Positivity Effect in Emotional Memory?.}, journal = {Experimental aging research}, volume = {44}, number = {5}, pages = {455-468}, doi = {10.1080/0361073X.2018.1521498}, pmid = {30355178}, issn = {1096-4657}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Aging/*psychology ; *Emotions ; Female ; Humans ; Male ; *Memory ; Middle Aged ; Young Adult ; }, abstract = {BACKGROUND: Typically, positive and negative emotional items are easier to remember than neutral ones. Charles, Mather, and Carstensen (2003) reported that older adults preferentially remember positive items, but this age-related "positivity effect" has not been replicated consistently.

METHODS: We conducted a close replication of Charles et al.'s study to verify that their method yields a clear positivity effect in older adults relative to the young. We also examined the role of attention, which has been argued to influence the presence of the positivity effect in older adults. We used a method similar to Charles et al. (2003). Young and older adults recalled pictures that had been encoded under full or divided attention.

RESULTS AND CONCLUSIONS: Older adults showed a positivity effect, but only under full attention. Young adults did not show any hint of a positivity effect, under either of the encoding conditions. The finding of a positivity effect in older but not young adults replicates the original report from Charles et al. (2003). The attention manipulation results suggest that when the positivity effect occurs in older adults' memory, it is attributable at least in part to cognitive control during encoding. Key terms: Emotional Enhancement of Memory-Divided attention-Aging.}, } @article {pmid30348785, year = {2018}, author = {Lindsey, PA and Miller, JRB and Petracca, LS and Coad, L and Dickman, AJ and Fitzgerald, KH and Flyman, MV and Funston, PJ and Henschel, P and Kasiki, S and Knights, K and Loveridge, AJ and Macdonald, DW and Mandisodza-Chikerema, RL and Nazerali, S and Plumptre, AJ and Stevens, R and Van Zyl, HW and Hunter, LTB}, title = {More than $1 billion needed annually to secure Africa's protected areas with lions.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {45}, pages = {E10788-E10796}, pmid = {30348785}, issn = {1091-6490}, mesh = {Africa ; Animals ; Conservation of Natural Resources/*economics/legislation & jurisprudence ; Datasets as Topic ; Ecosystem ; Lions/*physiology ; *Models, Statistical ; }, abstract = {Protected areas (PAs) play an important role in conserving biodiversity and providing ecosystem services, yet their effectiveness is undermined by funding shortfalls. Using lions (Panthera leo) as a proxy for PA health, we assessed available funding relative to budget requirements for PAs in Africa's savannahs. We compiled a dataset of 2015 funding for 282 state-owned PAs with lions. We applied three methods to estimate the minimum funding required for effective conservation of lions, and calculated deficits. We estimated minimum required funding as $978/km[2] per year based on the cost of effectively managing lions in nine reserves by the African Parks Network; $1,271/km[2] based on modeled costs of managing lions at ≥50% carrying capacity across diverse conditions in 115 PAs; and $2,030/km[2] based on Packer et al.'s [Packer et al. (2013) Ecol Lett 16:635-641] cost of managing lions in 22 unfenced PAs. PAs with lions require a total of $1.2 to $2.4 billion annually, or ∼$1,000 to 2,000/km[2], yet received only $381 million annually, or a median of $200/km[2] Ninety-six percent of range countries had funding deficits in at least one PA, with 88 to 94% of PAs with lions funded insufficiently. In funding-deficit PAs, available funding satisfied just 10 to 20% of PA requirements on average, and deficits total $0.9 to $2.1 billion. African governments and the international community need to increase the funding available for management by three to six times if PAs are to effectively conserve lions and other species and provide vital ecological and economic benefits to neighboring communities.}, } @article {pmid30348362, year = {2018}, author = {Willame, C and Lin, L and Vetter, V and Baril, L and Praet, N}, title = {Reply to Lee et al.'s letter to the editor pertaining to our publication entitled "Pain caused by measles, mumps, and rubella vaccines: A systematic literature review".}, journal = {Vaccine}, volume = {36}, number = {45}, pages = {6589-6590}, doi = {10.1016/j.vaccine.2018.08.025}, pmid = {30348362}, issn = {1873-2518}, } @article {pmid30348075, year = {2018}, author = {Wong, TKF and Ranjard, L and Lin, Y and Rodrigo, AG}, title = {HaploJuice : accurate haplotype assembly from a pool of sequences with known relative concentrations.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {389}, pmid = {30348075}, issn = {1471-2105}, support = {DP160103474//Australian Research Council (AU)/ ; }, mesh = {*Algorithms ; Base Sequence ; Computer Simulation ; Databases, Genetic ; Haplotypes/*genetics ; Humans ; }, abstract = {BACKGROUND: Pooling techniques, where multiple sub-samples are mixed in a single sample, are widely used to take full advantage of high-throughput DNA sequencing. Recently, Ranjard et al. (PLoS ONE 13:0195090, 2018) proposed a pooling strategy without the use of barcodes. Three sub-samples were mixed in different known proportions (i.e. 62.5%, 25% and 12.5%), and a method was developed to use these proportions to reconstruct the three haplotypes effectively.

RESULTS: HaploJuice provides an alternative haplotype reconstruction algorithm for Ranjard et al.'s pooling strategy. HaploJuice significantly increases the accuracy by first identifying the empirical proportions of the three mixed sub-samples and then assembling the haplotypes using a dynamic programming approach. HaploJuice was evaluated against five different assembly algorithms, Hmmfreq (Ranjard et al., PLoS ONE 13:0195090, 2018), ShoRAH (Zagordi et al., BMC Bioinformatics 12:119, 2011), SAVAGE (Baaijens et al., Genome Res 27:835-848, 2017), PredictHaplo (Prabhakaran et al., IEEE/ACM Trans Comput Biol Bioinform 11:182-91, 2014) and QuRe (Prosperi and Salemi, Bioinformatics 28:132-3, 2012). Using simulated and real data sets, HaploJuice reconstructed the true sequences with the highest coverage and the lowest error rate.

CONCLUSION: HaploJuice provides high accuracy in haplotype reconstruction, making Ranjard et al.'s pooling strategy more efficient, feasible, and applicable, with the benefit of reducing the sequencing cost.}, } @article {pmid30341949, year = {2019}, author = {Maughan, B and Barker, ED}, title = {The Earlier the Better? Pausing for Thought ….}, journal = {Child development}, volume = {90}, number = {1}, pages = {20-24}, doi = {10.1111/cdev.13168}, pmid = {30341949}, issn = {1467-8624}, mesh = {Child ; Early Intervention, Educational ; Humans ; *Parenting ; Parents ; *Problem Behavior ; }, abstract = {Is earlier intervention always superior? Using two complementary forms of meta-analysis, Gardner and colleagues find no support for the "earlier is better" hypothesis in outcomes of parenting programs for child behavior problems across the 2-11 year age range. This commentary explores possible methodological and substantive reasons for the pattern of their findings. We need additional careful analyses of this kind, assessing age variations in intervention effects across broader age ranges, and in other developmental domains, for strong tests of the "earlier is better" hypothesis. At this stage, however, Gardner et al.'s findings give us some pause for thought.}, } @article {pmid30326939, year = {2018}, author = {Checa, A}, title = {Ultrasonography, an operator-dependent modality versus dual-energy computed tomography (DECT) in the detection of chondrocalcinosis: with regard to Tanikawa et al.'s study.}, journal = {Journal of orthopaedic surgery and research}, volume = {13}, number = {1}, pages = {255}, pmid = {30326939}, issn = {1749-799X}, mesh = {Chondrocalcinosis/*diagnostic imaging ; Clinical Competence/*standards ; Humans ; Tomography, X-Ray Computed/methods/*standards ; Ultrasonography, Interventional/methods/*standards ; }, } @article {pmid30324769, year = {2019}, author = {Sawyer, A and Lewthwaite, H and Gucciardi, DF and Hill, K and Jenkins, S and Cavalheri, V}, title = {Behaviour change techniques to optimise participation in physical activity or exercise in adolescents and young adults with chronic cardiorespiratory conditions: a systematic review.}, journal = {Internal medicine journal}, volume = {49}, number = {10}, pages = {1209-1220}, doi = {10.1111/imj.14141}, pmid = {30324769}, issn = {1445-5994}, support = {//Curtin Research Fellowship/International ; //Cancer Council Western Australia Postdoctoral Research Fellowship/International ; //Sir Charles Gairdner Hospital/International ; //Australian Cystic Fibrosis Research Trust/International ; //Institute for Respiratory Health (Conquer Cystic Fibrosis Research Program)/International ; //Curtin University/International ; }, mesh = {Adolescent ; Adult ; Behavior Therapy/*methods ; Cardiovascular Diseases/*therapy ; Chronic Disease ; *Exercise ; Health Promotion ; Humans ; Life Style ; Lung Diseases/*therapy ; Middle Aged ; Randomized Controlled Trials as Topic ; Young Adult ; }, abstract = {Participation in regular physical activity decreases the risk of developing cardiometabolic disease. However, the proportion of people who participate in the recommended amount of physical activity is low, with common barriers including competing interests and inclement weather. In people with chronic cardiorespiratory conditions, participation in physical activity is reduced further by disease-specific barriers, time burden of treatment and unpleasant symptoms during physical activity. Addressing these barriers during adolescence and early adulthood may promote greater physical activity participation into older age. The aim of this review was to classify interventions aimed at optimising participation in physical activity as 'promising' or 'not promising' in people aged 15-45 years with chronic cardiorespiratory conditions and categorise the behaviour change techniques (BCT) within these interventions. Nine databases and registries were searched (October 2017) for studies that reported objective measures of physical activity before and after an intervention period. Interventions were classified as 'promising' if a between-group difference in physical activity was demonstrated. Michie et al.'s (2013) v1 Taxonomy was used to unpack the BCT within interventions. Across the six included studies (n = 396 participants), 19 (20%) of 93 BCT were described. The interventions of three studies were classified as 'promising'. The most commonly used BCT comprised goal setting, action planning and social support. Five BCT were solely used in 'promising' interventions. Our review demonstrated that only 20% of BCT have been utilised, and those BCT that were used only in 'promising' physical activity interventions in adolescents and adults with chronic cardiorespiratory conditions were isolated.}, } @article {pmid30316519, year = {2018}, author = {Lemoine, S and Chabernaud, JL and Briche, F and Renard, A and Jost, D and Tourtier, JP}, title = {Re: Gulati et al.'s article "Presetting ECG electrodes for earlier heart rate detection in the delivery room.": Prehospital use of ECG electrodes by nonmedical emergency professionals: An additional source of help during unexpected out-of-hospital births.}, journal = {Resuscitation}, volume = {132}, number = {}, pages = {e1}, doi = {10.1016/j.resuscitation.2018.05.029}, pmid = {30316519}, issn = {1873-1570}, mesh = {*Delivery Rooms ; Electrocardiography ; Electrodes ; *Emergency Medical Services ; Heart Rate ; Humans ; Infant, Newborn ; Pregnancy ; }, } @article {pmid30313768, year = {2018}, author = {Heads, SW}, title = {On the status of Araripegryllus romualdoi (Insecta: Orthoptera: Grylloidea) from the Cretaceous Santana Formation of Brazil.}, journal = {Zootaxa}, volume = {4486}, number = {1}, pages = {83-84}, doi = {10.11646/zootaxa.4486.1.6}, pmid = {30313768}, issn = {1175-5334}, mesh = {Animals ; Brazil ; *Fossils ; Gryllidae ; *Insecta ; }, abstract = {The fossil cricket Araripegryllus romualdoi was described by Freitas et al. (2016) based on a single, very poorly preserved specimen from the Romualdo Member of the Lower Cretaceous Santana Formation; a deposit famed for the exceptional preservation of vertebrates in carbonate concretions (Martill, 1996, 2007). While abundant and diverse in the underlying Crato Formation (Martill et al., 2007 and contributions therein), fossil insects had not been reported from the Santana Formation prior to Freitas et al.'s paper. The occurrence of an insect in the Santana Formation is certainly noteworthy, but the description of a new species and its placement in the genus Araripegryllus are problematic, primarily because of the very poor preservation of the specimen. Here, problems associated with the diagnosis and placement of A. romualdoi are outlined, and the species declared a nomen dubium.}, } @article {pmid30309500, year = {2018}, author = {Miquel, J and Poonlaphdecha, S and Ribas, A}, title = {Spermatological characteristics of the family Glypthelminthidae (Digenea, Plagiorchioidea) inferred from the ultrastructural study of Glypthelmins staffordi Tubangui, 1928.}, journal = {Tissue & cell}, volume = {54}, number = {}, pages = {114-119}, doi = {10.1016/j.tice.2018.08.013}, pmid = {30309500}, issn = {1532-3072}, mesh = {Animals ; Male ; Phylogeny ; Spermatozoa/*ultrastructure ; Trematoda/*classification/*ultrastructure ; }, abstract = {The present study describes the ultrastructural organization of the mature spermatozoon of the digenean Glypthelmins staffordi (Glypthelminthidae) by means of transmission electron microscopy. Live digeneans were collected from the Chinese edible frog (Hoplobatrachus rugulosus) in Udon Thani Province (Thailand). The ultrastructural study reveals that the mature spermatozoon of G. staffordi is a filiform cell, which is tapered at both extremities. It exhibits the Bakhoum et al.'s type IV of spermatozoon of digeneans characterized by the 9+'1' axonemes of trepaxonematan Platyhelminthes, the presence of the association "external ornamentation-cortical microtubules", the external ornamentation located in the posterior part of the anterior region, the arrangement of parallel cortical microtubules in two bundles and with its maximum number located in the anterior part of the sperm cell, and the presence of two mitochondria. Other characteristics are the presence of spine-like bodies, a posterior extremity containing only the nucleus, and the presence of a large amount of glycogen granules. Results of the present study are particularly compared with the existing data in other families of the Plagiorchioidea, namely the Brachycoeliidae, the Haematoloechidae, the Omphalometridae and the Plagiorchiidae.}, } @article {pmid30307268, year = {2018}, author = {Kinoshita, S and Gayed, M and Norris, D}, title = {Orthographic and phonological priming effects in the same-different task.}, journal = {Journal of experimental psychology. Human perception and performance}, volume = {44}, number = {11}, pages = {1661-1671}, pmid = {30307268}, issn = {1939-1277}, support = {MC_UU_00005/11/MRC_/Medical Research Council/United Kingdom ; //Australian Research Council/ ; }, mesh = {Adult ; Female ; Humans ; Male ; Middle Aged ; Pattern Recognition, Visual/*physiology ; Perceptual Masking/*physiology ; Phonetics ; *Psycholinguistics ; Reading ; Young Adult ; }, abstract = {Masked priming tasks have been used widely to study early orthographic processes-the coding of letter position and letter identity. Recently, using masked priming in the same-different task Lupker, Nakayama, and Perea (2015a) reported finding a phonological priming effect with primes presented in Japanese Katakana, and English target words presented in the Roman alphabet, and based on this finding, suggested that previously reported effects in the same-different task in the literature could be based on phonology rather than orthography. In this article, the authors explain why the design of Lupker et al.'s experiment does not address this question; they then report 2 new experiments that do. The results indicate that the priming produced by orthographically similar primes in the same-different task for letter strings presented in the Roman alphabet is almost exclusively orthographic in origin, and phonology makes little contribution. The authors offer an explanation for why phonological priming was observed when the prime and target are presented in different scripts but not when they are presented in the same script. (PsycINFO Database Record (c) 2018 APA, all rights reserved).}, } @article {pmid30306415, year = {2018}, author = {Darnaud, L and Lamoureux, F and Godet, C and Pontier, S and Debard, A and Venisse, N and Martins, P and Concordet, D and Gandia, P}, title = {Isavuconazole Kinetic Exploration for Clinical Practice.}, journal = {Drugs in R&D}, volume = {18}, number = {4}, pages = {317-321}, pmid = {30306415}, issn = {1179-6901}, mesh = {Administration, Oral ; Adult ; Aged ; Antifungal Agents/administration & dosage/metabolism/*pharmacokinetics ; Cytochrome P-450 CYP3A/genetics ; Female ; Humans ; Kinetics ; Male ; Middle Aged ; Nitriles/administration & dosage/metabolism/*pharmacokinetics ; Polymorphism, Genetic/genetics ; Pyridines/administration & dosage/metabolism/*pharmacokinetics ; Triazoles/administration & dosage/metabolism/*pharmacokinetics ; }, abstract = {BACKGROUND: Isavuconazole is a new antifungal prodrug for the treatment of invasive aspergillosis and mucormycosis. As no clear pharmacokinetic-pharmacodynamic relationship has been established for patients, therapeutic drug monitoring is not currently required. However, as isavuconazole is a new drug, clinicians are sometimes sceptical about the exposure achieved in their patients and seek pharmacokinetic exploration. A minimal response consists of determining that the patient's pharmacokinetic profile agrees with profiles reported by Desai et al. using concentrations from the SECURE study.

METHODS: Based on one concentration and Desai et al.'s population-pharmacokinetic model, it is possible to estimate a patient's most likely pharmacokinetic profile. If a patient's pharmacokinetic profile is close to the profiles reported by Desai et al., therapeutic drug monitoring is not required. In contrast, when the pharmacokinetic profile differs from the Desai et al. profiles, isavuconazole concentration monitoring and pharmacokinetic profile modeling are the only methods for obtaining information on a patient's exposure and the efficacy of isavuconazole.

RESULTS: Four patients presented with surprising pharmacokinetic profiles, unexplained by drug interactions or cytochrome P450 3A4/5 polymorphisms. For two of them, a drug dosage adjustment was proposed and applied by clinicians, together with a check for a new pharmacokinetic profile a few days later.

CONCLUSIONS: Collecting one blood sample just before the first maintenance dose to make an early estimation of the patient's most likely pharmacokinetic profile is one method of identifying patients with outlier pharmacokinetic behavior.}, } @article {pmid30306136, year = {2018}, author = {Artelle, KA and Reynolds, JD and Treves, A and Walsh, JC and Paquet, PC and Darimont, CT}, title = {Working constructively toward an improved North American approach to wildlife management.}, journal = {Science advances}, volume = {4}, number = {10}, pages = {eaav2571}, pmid = {30306136}, issn = {2375-2548}, mesh = {Animals ; Animals, Wild/*physiology ; Communication ; *Conservation of Natural Resources ; Humans ; North America ; Public Opinion ; Science ; United States ; }, abstract = {Mawdsley et al. (2018) respond disapprovingly to our 2018 review of 667 wildlife management systems across Canada and the United States, which found that many of these systems lacked the scientific hallmarks of clear objectives, evidence, transparency, and independent review. Although we strongly agree with several of Mawdsley et al.'s points about the role of science in management, their response suggests confusion about three elements of our approach that we clarify herein: (i) the selection of hallmarks, (ii) the role of science in wildlife management, and (iii) our engagement with wildlife agencies. We contend that both critics and defenders of the current approach to wildlife management in Canada and the United States similarly desire rigorous management that achieves social and ecological benefits. Our original study-which used a clear approach to define hallmarks of science-based management, employed a reasonable set of indicator criteria to test for them, and was based on data available to the general public on whose behalf management is conducted-found evidence that the current approach falls short. However, it also provided a framework for addressing shortcomings moving forward. We suggest that advancing discussion on the operational role of science in management, including clarifying what "science-based management" actually means, could curtail practitioners and critics of the status quo talking over each other's heads and encourage all parties to work constructively to improve the governance of wildlife at a continental scale.}, } @article {pmid30300844, year = {2018}, author = {Dai, F and Yan, WJ and Fu, X and Zheng, YL and Du, YT and Bao, XZ and Kang, YF and Jin, XL and Zhou, B}, title = {Designing dichlorobinaphthoquinone as a prooxidative anticancer agent based on hydrogen peroxide-responsive in situ production of hydroxyl radicals.}, journal = {European journal of medicinal chemistry}, volume = {159}, number = {}, pages = {317-323}, doi = {10.1016/j.ejmech.2018.09.075}, pmid = {30300844}, issn = {1768-3254}, mesh = {Antineoplastic Agents/chemical synthesis/chemistry/*pharmacology ; Cell Line ; Cell Proliferation/drug effects ; Dose-Response Relationship, Drug ; *Drug Design ; Drug Screening Assays, Antitumor ; Humans ; Hydrogen Peroxide/chemistry/metabolism/*pharmacology ; Hydroxyl Radical/chemistry/metabolism/*pharmacology ; Molecular Structure ; Quinones/chemical synthesis/chemistry/*pharmacology ; Structure-Activity Relationship ; }, abstract = {Compared with normal cells, cancer cells harbor increased levels of reactive oxygen species (ROS) including hydrogen peroxide (H2O2), and therefore are more vulnerable to further ROS production. This biochemical difference favors the idea of developing new powerful selective prooxidative anticancer agents. However, it still remains a challenge to design them by targeting this difference. Herein, we report the designed dichlorobinaphthoquinone as a prooxidative anticancer agent which is capable of exploiting increased levels of H2O2 of cancer cells to produce in situ lethal hydroxyl radicals (HO•) and thereby kill them selectively, a design strategy inspired from Zhu et al.'s work on the molecular mechanism for metal-independent production of HO•.}, } @article {pmid30300362, year = {2018}, author = {Li, S and Wu, X and Zhao, D and Li, A and Tian, Z and Yang, X}, title = {An efficient dynamic ID-based remote user authentication scheme using self-certified public keys for multi-server environments.}, journal = {PloS one}, volume = {13}, number = {10}, pages = {e0202657}, pmid = {30300362}, issn = {1932-6203}, mesh = {Algorithms ; *Biometric Identification ; Certification ; Computer Security/*trends ; Computers ; Confidentiality ; *Health Smart Cards ; Humans ; Telemedicine ; *User-Computer Interface ; }, abstract = {Recently, Li et al. proposed a novel smart card and dynamic ID-based remote user authentication scheme for multi-server environments. They claimed that their scheme can resist several types of attacks. However, through careful analysis, we find that Li et al.'s scheme is vulnerable to stolen smart card and off-line dictionary attacks, replay attacks, impersonation attacks and server spoofing attacks. By analyzing other similar schemes, we find that a certain type of dynamic ID-based multi-server authentication scheme in which only hash functions are used and whereby no registration center participates in the authentication and session key agreement phase faces difficulties in providing perfectly efficient and secure authentication. To compensate for these shortcomings, we propose a novel dynamic ID-based remote user authentication scheme for multi-server environments based on pairing and self-certified public keys. Security and performance analyses show that the proposed scheme is secure against various attacks and has many excellent features.}, } @article {pmid30299161, year = {2018}, author = {Clark, MG and Smallwood Shoukry, R and Huang, CJ and Danielian, LE and Bageac, D and Floeter, MK}, title = {Loss of functional connectivity is an early imaging marker in primary lateral sclerosis.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {19}, number = {7-8}, pages = {562-569}, pmid = {30299161}, issn = {2167-9223}, support = {Z01 NS002976/ImNIH/Intramural NIH HHS/United States ; ZIA NS002976/ImNIH/Intramural NIH HHS/United States ; }, mesh = {Adult ; Aged ; Amyotrophic Lateral Sclerosis/*diagnostic imaging/*pathology ; Cerebral Cortex/diagnostic imaging ; Disease Progression ; Electromyography ; Female ; Humans ; Image Processing, Computer-Assisted ; Longitudinal Studies ; *Magnetic Resonance Imaging ; Male ; Middle Aged ; Neural Pathways/*diagnostic imaging ; Oxygen/blood ; Statistics, Nonparametric ; White Matter/diagnostic imaging ; }, abstract = {OBJECTIVE: The clinical diagnosis of primary lateral sclerosis can only be made after upper motor neuron symptoms have progressed for several years without developing lower motor neuron signs. The goal of the study was to identify neuroimaging changes that occur early in primary lateral sclerosis, prior to clinical diagnosis.

METHODS: MRI scans were obtained on 13 patients with adult-onset progressive spasticity for five years or less who were followed longitudinally to confirm a clinical diagnosis of primary lateral sclerosis. Resting state functional MRI, diffusion tensor imaging, and anatomical images were obtained. These "pre-PLS" patients were compared to 18 patients with longstanding, established primary lateral sclerosis and 28 controls.

RESULTS: Pre-PLS patients had a marked reduction in seed-based resting-state motor network connectivity compared to the controls and patients with longstanding disease. White matter regions with reduced fractional anisotropy were similar in the two patient groups compared to the controls. Patients with longstanding disease had cortical thinning of the precentral gyrus. A slight thinning of the right precentral gyrus was detected in initial pre-PLS patients' scans. Follow-up scans in eight pre-PLS patients 1-2 years later showed increasing motor connectivity, thinning of the precentral gyrus, and no change in diffusion measures of the corticospinal tract or callosal motor region.

CONCLUSIONS: Loss of motor functional connectivity is an early imaging marker in primary lateral sclerosis. This differs from literature descriptions of amyotrophic lateral sclerosis, warranting further studies to test whether resting-state functional MRI can differentiate between amyotrophic lateral sclerosis and primary lateral sclerosis at early disease stages.}, } @article {pmid30298716, year = {2018}, author = {Liu, Q and Xiao, B and Cheng, JB and Li, YC and Li, QZ and Li, WZ and Xu, XF and Yu, XF}, title = {Carbon Excess C3N: A Potential Candidate as Li-Ion Battery Material.}, journal = {ACS applied materials & interfaces}, volume = {10}, number = {43}, pages = {37135-37141}, doi = {10.1021/acsami.8b14183}, pmid = {30298716}, issn = {1944-8252}, abstract = {Xu et al.'s recent experimental work (Adv. Mater. 2017, 29, 1702007) suggested that C3N is a potential candidate as Li-ion battery with unusual electrochemical characteristics. However, the obvious capacity loss (from 787.3 to 383.3 mA h·g[-1]) occurs after several cycles, which restricts its high performance. To understand and further solve this issue, in the present study, we have studied the intercalation processes of Li ions into C3N via first-principle simulations. The results reveal that the Li-ion theoretical capacity in pure C3N is only 133.94 mA h·g[-1], the value is obviously lower than experimental one. After examining the experimental results in detail, it is found that the chemical component of the as-generated C xN structure is actually C2.67N with N excess. In this case, the calculated theoretical capacity is 837.06 mA h·g[-1], while part of Li ions are irreversibly trapped in C2.67N, resulting in the capacity loss. This phenomenon is consistent with the experimental results. Accordingly, we suggest that N excess C3N, but not pure C3N, is the proposed Li-ion battery material in Xu et al.'s experiment. To solve the capacity loss issue and maintain the excellent performance of C3N-based anode material, the C3N with slightly excess C (C3.33N), which has been successfully fabricated in the experiment, is considered in view of its relatively low chemical activity as compared with N excess C3N. Our results reveal that the C excess C3N is a potential Li-ion battery material, which exhibits the low open circle voltage (0.12 V), high reversible capacity (840.35 mA h·g[-1]), fast charging/discharging rate, and good electronic conductivity.}, } @article {pmid30297151, year = {2019}, author = {Andersson, M and Wilde-Larsson, B and Persenius, M}, title = {Intensive care nurses fail to translate knowledge and skills into practice - A mixed-methods study on perceptions of oral care.}, journal = {Intensive & critical care nursing}, volume = {52}, number = {}, pages = {51-60}, doi = {10.1016/j.iccn.2018.09.006}, pmid = {30297151}, issn = {1532-4036}, mesh = {Adult ; Aged ; Clinical Competence/standards/statistics & numerical data ; Female ; *Health Knowledge, Attitudes, Practice ; Humans ; Intensive Care Units/organization & administration/statistics & numerical data ; Male ; Middle Aged ; Nurses ; Oral Health/*standards ; *Perception ; Surveys and Questionnaires ; }, abstract = {OBJECTIVES: To identify intensive care nurses' perceptions of oral care according to Coker et al.'s (2013) conceptual framework and to contribute to the knowledge base of oral care in intensive care.

DESIGN/METHODS: This was a concurrent embedded mixed-methods design, with more weight given to the quantitative part. Participants responded to the Nursing Care related to Oral Health questionnaire, including perceptions of oral care antecedents (18 items), defining attributes (17 items), and consequences (6 items) and two open-ended questions. The data were analysed with descriptive and correlation statistics and qualitative content analysis.

SETTING: Intensive care nurses (n = 88) in six general intensive care units.

RESULTS: Intensive care nurses perceived that an important part of nursing care was oral care, especially to intubated patients. They perceived that the nursing staff was competent in oral care skills and had access to different kinds of equipment and supplies to provide oral care. The oral cavity was inspected on a daily basis, mostly without the use of any assessment instruments. Oral care seemed to be task-oriented, and documentation of the patients' experiences of the oral care process was rare.

CONCLUSIONS: The antecedents, knowledge and skills are available to provide quality oral care, but intensive care nurses seem to have difficulties translating these components into practice. Thus they might have to shift their task-oriented approach towards oral care to a more person-centred approach in order to be able to meet patients' needs.}, } @article {pmid30291419, year = {2018}, author = {Scheffler, L and Kovacs, P and Fasano, A and Heiker, JT}, title = {Letter to the Editor regarding Mörkl et al.'s paper: Gut microbiota, dietary intakes and intestinal permeability reflected by serum zonulin in women.}, journal = {European journal of nutrition}, volume = {57}, number = {8}, pages = {2999-3000}, pmid = {30291419}, issn = {1436-6215}, mesh = {Cholera Toxin ; Female ; *Gastrointestinal Microbiome ; Haptoglobins ; Humans ; Intestines ; Permeability ; Protein Precursors ; }, } @article {pmid30289897, year = {2018}, author = {Xie, Q and Lu, Y and Tan, X and Tang, Z and Hu, B}, title = {Security and efficiency enhancement of an anonymous three-party password-authenticated key agreement using extended chaotic maps.}, journal = {PloS one}, volume = {13}, number = {10}, pages = {e0203984}, pmid = {30289897}, issn = {1932-6203}, mesh = {Algorithms ; Biometric Identification ; *Computer Security ; Confidentiality ; Humans ; }, abstract = {Recently, Lu et al. claimed that Xie et al.'s three-party password-authenticated key agreement protocol (3PAKA) using chaotic maps has three security vulnerabilities; in particular, it cannot resist offline password guessing attack, Bergamo et al.'s attack and impersonation attack, and then they proposed an improved protocol. However, we demonstrate that Lu et al.'s attacks on Xie et al.'s scheme are unworkable, and their improved protocol is insecure against stolen-verifier attack and off-line password guessing attack. Furthermore, we propose a novel scheme with enhanced security and efficiency. We use formal verification tool ProVerif, which is based on pi calculus, to prove security and authentication of our scheme. The efficiency of the proposed scheme is higher than other related schemes.}, } @article {pmid30286748, year = {2018}, author = {Gionfriddo, MR}, title = {Balancing feasibility and comprehensiveness: examining medications for reducing emergency hospital admissions.}, journal = {BMC medicine}, volume = {16}, number = {1}, pages = {169}, pmid = {30286748}, issn = {1741-7015}, mesh = {*Hospitalization ; Humans ; }, abstract = {Emergency hospital admissions are common, with several interventions having been developed to reduce their rates. Bobrovitz et al. summarized the available body of evidence regarding pharmacologic therapies aimed at reducing emergency hospital admissions, and identified 28 medications for which high- or moderate-quality evidence supports their use, 11 of which were identified as being supported by current guideline recommendations. Additionally, the authors identified 28 medications supported by low- or very low-quality evidence, which can serve as targets for future research. The article by Bobrovitz et al. presents a good summary of the evidence, albeit with limitations in the search strategy that cannot guarantee the review as comprehensive. Despite this, the review has important implications for policymakers, guideline panels, researchers, clinicians, and funders since the identified medications can either be targets for quality improvement initiatives or for future research. Bobrovitz et al.'s review highlights the challenge that systematic reviewers face when balancing feasibility and comprehensiveness.Please see related article: https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-018-1104-9.}, } @article {pmid30277104, year = {2018}, author = {Read, J and Miller, N and Kitsou, N}, title = {Is there an order of loss of sounds in speakers with Parkinson's disease?.}, journal = {Clinical linguistics & phonetics}, volume = {32}, number = {11}, pages = {997-1011}, doi = {10.1080/02699206.2018.1504989}, pmid = {30277104}, issn = {1464-5076}, mesh = {Adult ; Aged ; Dysarthria/*psychology ; Female ; Humans ; Male ; Parkinson Disease/*physiopathology ; *Severity of Illness Index ; *Speech Intelligibility ; }, abstract = {Influential reports on speech changes in people with Parkinson's disease (PD; Logemann et al., 1978, 1981) reported a posterior to anterior pattern of loss of speech sound accuracy. These claims have never been examined. In a partial replication of Logemann et al.'s work, we examined whether posterior lingual sounds are most affected in people with Parkinson's disease, followed by anterior lingual sounds and then labial sounds. Ninety-nine people with PD (age: mean 70.7, SD 8.46; time since diagnosis: mean 6.97, SD 6.2) with mild to severe overall motor symptoms (Hoehn and Yahr stages 1-5, median 2.5) completed a diagnostic intelligibility test. This was scored by 60 listeners unfamiliar with PD and dysarthric speech. We calculated the proportion of posterior versus anterior lingual versus labial sounds misrecognized by the listeners. We compared profiles of misperceived sounds within and across Hoehn and Yahr stages of severity and in relation to Unified Parkinson's Disease Rating Scale (UPDRS) and speech intelligibility scores. Speech accuracy declined significantly in relation to overall motor impairment for labial and anterior lingual sounds but not for velar sounds. Speech sound accuracy was strongly associated with intelligibility outcomes (p = < 0.01). Contrary to previous assertions, there was no evidence supporting the existence of a posterior to anterior order of 'loss' of oral speech sounds in people with PD, nor an interaction of anterior-posterior speech profile changes with Hoehn and Yahr stage. Findings support the notion that a common underlying impairment of movement downscaling affects all sounds similarly and simultaneously in PD from the start.}, } @article {pmid30269243, year = {2018}, author = {Mouchet, J and Bégaud, B}, title = {Authors' Reply to Cohen et al.'s Comment on "Central Demyelinating Diseases after Vaccination Against Hepatitis B Virus: A Disproportionality Analysis within the VAERS Database".}, journal = {Drug safety}, volume = {41}, number = {12}, pages = {1429-1430}, pmid = {30269243}, issn = {1179-1942}, mesh = {Databases, Factual ; Demyelinating Diseases ; Hepatitis B ; *Hepatitis B virus ; Humans ; *Vaccination ; }, } @article {pmid30265072, year = {2020}, author = {Bhattarai, JJ and Oehlert, ME and Weber, DK}, title = {Psychometric properties of the Mississippi Scale for Combat-Related Posttraumatic Stress Disorder based on veterans' period of service.}, journal = {Psychological services}, volume = {17}, number = {1}, pages = {75-83}, doi = {10.1037/ser0000285}, pmid = {30265072}, issn = {1939-148X}, support = {//Veterans Affairs Eastern Kansas Healthcare System/ ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Combat Disorders/*diagnosis ; Humans ; Male ; Middle Aged ; Psychiatric Status Rating Scales/*standards ; Psychometrics/*standards ; Retrospective Studies ; Sensitivity and Specificity ; Stress Disorders, Post-Traumatic/*diagnosis ; United States ; United States Department of Veterans Affairs ; *Veterans ; }, abstract = {The Mississippi Scale for Combat-Related Posttraumatic Stress Disorder (M-PTSD) is a 35-item screening instrument for combat-related PTSD (Keane, Caddell, & Taylor, 1988) that has been normed largely on veterans from the Vietnam era. Research on its psychometric properties with veterans across different periods of service (POS) remains limited; however, this is an important research endeavor because of the uniqueness in experiences across eras which may influence PTSD rates, symptom expression/complaints, and treatment completion/outcomes. In this study, our objective was to examine the instrument's properties, replicating Keane et al.'s (1988) methodologies, with veterans from World War II, Korean, Vietnam, post-Vietnam, and Persian Gulf (pre- and post-9/11) eras. This retrospective cohort study involved the examination of medical records of 29,280 veterans receiving care across Veterans Affairs medical outpatient centers nationwide. The data revealed significant differences across POS in terms of M-PTSD total scores, F(4, 29,275) = 55.01, p = .000; therefore, analyses were conducted with the entire sample and with each POS. The instrument demonstrated high internal consistency with our sample (α = .92) and across POS (.91 to .92). Receiver operating characteristic curves identified cut-scores ranging from 86 to 112 across the POS with acceptable-to-good sensitivity (68% to 81%) and fair-to-acceptable specificity (61% to 70%), with lower scores among World War II and Korean era veterans compared with veterans from more recent conflicts. In terms of clinical implications, the M-PTSD is a brief, easily accessible, valuable screening tool for combat-related PTSD in veterans across a range of POS. Future studies should consider the methodologies utilized to diagnose PTSD and how this potentially impacts the instrument's properties. (PsycINFO Database Record (c) 2020 APA, all rights reserved).}, } @article {pmid30258732, year = {2018}, author = {Brown, NJL and Coyne, JC}, title = {Does Twitter language reliably predict heart disease? A commentary on Eichstaedt et al. (2015a).}, journal = {PeerJ}, volume = {6}, number = {}, pages = {e5656}, pmid = {30258732}, issn = {2167-8359}, abstract = {We comment on Eichstaedt et al.'s (2015a) claim to have shown that language patterns among Twitter users, aggregated at the level of US counties, predicted county-level mortality rates from atherosclerotic heart disease (AHD), with "negative" language being associated with higher rates of death from AHD and "positive" language associated with lower rates. First, we examine some of Eichstaedt et al.'s apparent assumptions about the nature of AHD, as well as some issues related to the secondary analysis of online data and to considering counties as communities. Next, using the data files supplied by Eichstaedt et al., we reproduce their regression- and correlation-based models, substituting mortality from an alternative cause of death-namely, suicide-as the outcome variable, and observe that the purported associations between "negative" and "positive" language and mortality are reversed when suicide is used as the outcome variable. We identify numerous other conceptual and methodological limitations that call into question the robustness and generalizability of Eichstaedt et al.'s claims, even when these are based on the results of their ridge regression/machine learning model. We conclude that there is no good evidence that analyzing Twitter data in bulk in this way can add anything useful to our ability to understand geographical variation in AHD mortality rates.}, } @article {pmid30248898, year = {2018}, author = {Yu, S and Lee, J and Lee, K and Park, K and Park, Y}, title = {Secure Authentication Protocol for Wireless Sensor Networks in Vehicular Communications.}, journal = {Sensors (Basel, Switzerland)}, volume = {18}, number = {10}, pages = {}, pmid = {30248898}, issn = {1424-8220}, abstract = {With wireless sensor networks (WSNs), a driver can access various useful information for convenient driving, such as traffic congestion, emergence, vehicle accidents, and speed. However, a driver and traffic manager can be vulnerable to various attacks because such information is transmitted through a public channel. Therefore, secure mutual authentication has become an important security issue, and many authentication schemes have been proposed. In 2017, Mohit et al. proposed an authentication protocol for WSNs in vehicular communications to ensure secure mutual authentication. However, their scheme cannot resist various attacks such as impersonation and trace attacks, and their scheme cannot provide secure mutual authentication, session key security, and anonymity. In this paper, we propose a secure authentication protocol for WSNs in vehicular communications to resolve the security weaknesses of Mohit et al.'s scheme. Our authentication protocol prevents various attacks and achieves secure mutual authentication and anonymity by using dynamic parameters that are changed every session. We prove that our protocol provides secure mutual authentication by using the Burrows[-]Abadi[-]Needham logic, which is a widely accepted formal security analysis. We perform a formal security verification by using the well-known Automated Validation of Internet Security Protocols and Applications tool, which shows that the proposed protocol is safe against replay and man-in-the-middle attacks. We compare the performance and security properties of our protocol with other related schemes. Overall, the proposed protocol provides better security features and a comparable computation cost. Therefore, the proposed protocol can be applied to practical WSNs-based vehicular communications.}, } @article {pmid30240444, year = {2018}, author = {Capps, R and Gelatt, J and Van Hook, J and Fix, M}, title = {Commentary on "The number of undocumented immigrants in the United States: Estimates based on demographic modeling with data from 1990-2016".}, journal = {PloS one}, volume = {13}, number = {9}, pages = {e0204199}, pmid = {30240444}, issn = {1932-6203}, mesh = {Censuses ; Demography ; Humans ; Models, Statistical ; Undocumented Immigrants/*statistics & numerical data ; United States ; }, abstract = {"The number of undocumented immigrants in the United States: Estimates based on demographic modeling with data from 1990-2016" by Fazel-Zarandi, Feinstein and Kaplan presents strikingly higher estimates of the unauthorized immigrant population than established estimates using the residual method. Fazel-Zarandi et. al.'s estimates range from a low or "conservative" number of 16.7 million unauthorized immigrants, to an "average" of 22.1 million, and to a high of 27.5 million. The Pew Hispanic Center estimated the population at 11.3 million in 2016, and the Department of Homeland Security (DHS) estimated it at 12.3 million. The new method shows much more rapid growth in unauthorized immigration during the 1990s and a substantially higher population in 2000 (13.3 million according to their "conservative" model) than Pew (8.6 million) and DHS (8.5 million). In this commentary, we explain that such an estimate for 2000 is implausible, as it suggests that the 2000 Census undercounted the unauthorized immigrant population by at least 42% in the 2000 Census, and it is misaligned with other demographic data. Fazel-Zarandi, Feinstein and Kaplan's model produces estimates that have a 10 million-person range in 2016, far too wide to be useful for public policy purposes; their estimates are not benchmarked against any external data sources; and their model appears to be driven by assumptions about return migration of unauthorized immigrants during the 1990s. Using emigration rates from the binational Mexican Migration Project survey for the illegal border-crosser portion of the unauthorized population, we generate a 2000 unauthorized population estimate of 8.2 million-slightly below Pew and DHS's estimates-without changing other assumptions in the model. We conclude that this new model's estimates are highly sensitive to assumptions about emigration, and moreover, that the knowledge base about emigration in the unauthorized population during the 1990s is not well enough developed to support the model underlying their estimates.}, } @article {pmid30237059, year = {2019}, author = {Brooks, LA and Bloomer, MJ and Manias, E}, title = {Culturally sensitive communication at the end-of-life in the intensive care unit: A systematic review.}, journal = {Australian critical care : official journal of the Confederation of Australian Critical Care Nurses}, volume = {32}, number = {6}, pages = {516-523}, doi = {10.1016/j.aucc.2018.07.003}, pmid = {30237059}, issn = {1036-7314}, mesh = {*Communication ; *Cultural Competency ; Humans ; *Intensive Care Units ; Professional-Family Relations ; Professional-Patient Relations ; *Terminal Care ; }, abstract = {OBJECTIVES: The objectives of this systematic review were the following: (i) to describe whether culturally sensitive communication is used by clinicians (nurses and physicians) when communicating with patients and families at the end-of-life in the intensive care unit and (ii) to evaluate the impact of culturally sensitive communication at the end-of-life. The systematic review question was how is culturally sensitive communication used by clinicians when communicating with patients and families at the end-of-life in the intensive care unit?

DATA SOURCES: A search of CINAHL, MEDLINE, Embase, and PsycINFO databases identified all peer-reviewed research evidence published in English between January 1994 and November 2017. Two authors independently assessed articles for inclusion. From the 124 articles resulting from the search, nine were included in this systematic review.

REVIEW METHODS: Articles were independently assessed for quality by two authors using Caldwell et al.'s framework to critique health research. The data available in this systematic review were heterogeneous, with varied study designs and outcome measures, making the data unsuitable for meta-analysis. The most appropriate method for data synthesis for this systematic review was narrative synthesis.

RESULTS: From the narrative synthesis, two major themes emerged: communication barriers and cultural and personal influences on culturally sensitive communication. Communication barriers were identified in eight studies, influencing the timing and quality of culturally sensitive communication at the end-of-life. Cultural and personal influences on communication at the end-of-life was present in eight studies.

CONCLUSIONS: The findings of this systematic review show that clinicians lack the knowledge to enable effective interaction with culturally diverse patients and families at the end-of-life.}, } @article {pmid30233353, year = {2018}, author = {López-Higes, R and Prados, JM and Rubio-Valdehita, S and Rodríguez-Rojo, I and de Frutos-Lucas, J and Montenegro, M and Montejo, P and Prada, D and Losada, MLD}, title = {Factors Explaining Language Performance After Training in Elders With and Without Subjective Cognitive Decline.}, journal = {Frontiers in aging neuroscience}, volume = {10}, number = {}, pages = {264}, pmid = {30233353}, issn = {1663-4365}, abstract = {The present study explores if cognitive reserve, executive functions, and working memory capacity are predictive of performance in the language domain (specifically in sentence comprehension and naming) after a cognitive training intervention. Sixty-six Spanish older adults voluntarily participated in the study, classified either as older adults with subjective cognitive decline according to Jessen et al.'s (2014) criteria (n = 35; 70.94 ± 4.16 years old) or cognitively intact (n = 31; 71.34 ± 4.96 years old). Written sentence comprehension and visual confrontation naming were assessed both immediately after recruitment (at the baseline), and then 6 months later, once each participant had completed his/her cognitive training (a well-known program in Spain, called UMAM; English translation: Madrid City Council Memory Unit Program). Cognitive reserve, executive functions (cognitive flexibility and controlled interference efficiency), and working memory capacity were measured for all participants at the baseline. Results pointed out that the subjective cognitive decline group presented greater benefits in the language domain than cognitively intact participants. We also observed that lower executive functioning and working memory capacity at the baseline predicted larger benefits in language performance after training, but only in the group of cognitively intact older adults. However, selected predictors hardly explained subjective cognitive decline participants' results in language performance after training.}, } @article {pmid30222617, year = {2019}, author = {Akyuz, G and Giray, E}, title = {Noninvasive neuromodulation techniques for the management of phantom limb pain: a systematic review of randomized controlled trials.}, journal = {International journal of rehabilitation research. Internationale Zeitschrift fur Rehabilitationsforschung. Revue internationale de recherches de readaptation}, volume = {42}, number = {1}, pages = {1-10}, doi = {10.1097/MRR.0000000000000317}, pmid = {30222617}, issn = {1473-5660}, mesh = {Humans ; Phantom Limb/*therapy ; Randomized Controlled Trials as Topic ; *Transcranial Direct Current Stimulation ; *Transcranial Magnetic Stimulation ; }, abstract = {Neuromodulation techniques work by modulating pain perception by inducing changes in polarity of the neuronal membrane and thereby cortical excitability. The aim of this review is to evaluate the efficiency and safety of noninvasive neuromodulation techniques for phantom limb pain (PLP). A systematic literature search in the PubMed, Scopus, Web of Science, and Cochrane Library databases was performed to identify studies investigating the effects of noninvasive neuromodulation for PLP. The included journal articles were assessed with Furlan et al.'s method for examining the risk of bias to assess methodologic quality, and evidence was graded using the GRADE approach. The literature search identified 239 studies. Of these 239, four studies fulfilled the inclusion criteria and were included for data extraction. Two of the studies focused on repetitive transcranial magnetic stimulation (rTMS) whereas two other concentrated on transcranial direct current stimulation (tDCS). The present review showed that there is conflicting evidence to support the use of tDCS in short term and moderate evidence to support the use of rTMS in immediate and short term. It is important to recognize that this evidence comes from a very small sample size. No serious adverse effects were reported. Further information from randomized controlled trials with larger sample size investigating immediate and short-term and long-term effects are needed to clarify the best effective stimulation parameters and number of sessions of tDCS and rTMS for PLP.}, } @article {pmid30221464, year = {2018}, author = {Duffy, A and Grof, P}, title = {Commentary on McGorry et al.'s Debate on: "Is 'early intervention' in bipolar disorder what it claims to be?".}, journal = {Bipolar disorders}, volume = {20}, number = {6}, pages = {556-557}, doi = {10.1111/bdi.12643}, pmid = {30221464}, issn = {1399-5618}, support = {PJ 152967//CIHR/Canada ; }, mesh = {Bipolar Disorder/*therapy ; Disease Progression ; Humans ; }, } @article {pmid30220959, year = {2018}, author = {de Vries, RE and Hilbig, BE and Zettler, I and Dunlop, PD and Holtrop, D and Lee, K and Ashton, MC}, title = {Honest People Tend to Use Less-Not More-Profanity: Comment on Feldman et al.'s (2017) Study 1.}, journal = {Social psychological and personality science}, volume = {9}, number = {5}, pages = {516-520}, pmid = {30220959}, issn = {1948-5506}, abstract = {This article shows that the conclusion of Feldman et al.'s (2017) Study 1 that profane individuals tend to be honest is most likely incorrect. We argue that Feldman et al.'s conclusion is based on a commonly held but erroneous assumption that higher scores on Impression Management Scales, such as the Lie Scale, are associated with trait dishonesty. Based on evidence from studies that have investigated (1) self-other agreement on Impression Management Scales, (2) the relation of Impression Management Scales with personality variables, and (3) the relation of Impression Management Scales with objective measures of cheating, we show that high scores on Impression Management Scales are associated with high-instead of low-trait honesty when measured in low-stakes conditions. Furthermore, using two data sets that included an "I never swear" item, we show that profanity use is negatively related to other reports of HEXACO honesty-humility and positively related to actual cheating.}, } @article {pmid30218875, year = {2018}, author = {Jasiulionis, M and Balčiauskas, L and Balčiauskienė, L and Taraškevičius, R}, title = {Accumulation of chemical elements in yellow-necked mice under a colony of great cormorants.}, journal = {Chemosphere}, volume = {213}, number = {}, pages = {156-163}, doi = {10.1016/j.chemosphere.2018.09.025}, pmid = {30218875}, issn = {1879-1298}, mesh = {Animals ; Environmental Pollutants/analysis/*chemistry ; Female ; Male ; Mice ; }, abstract = {This study represents the first investigation into the accumulation of chemical elements in small mammals inhabiting the territory of a great cormorant colony. Trapping was done in the Juodkrantė great cormorant colony, one of the largest colonies in Europe. The accumulation of 20 chemical elements in the bodies (muscle and bones) of yellow-necked mice (Apodemus flavicollis) was investigated using the energy-dispersive x-ray fluorescence equipment Spectro Xepos HE. Two groups of positively inter-correlated chemical elements (Mg, Al, P, Ca and Al, S, Cl, K) were identified. The concentrations of five elements differed significantly between mice trapped in different zones of the colony with differing intensities of cormorant influence: the values of K and Cu in A. flavicollis increased in line with an increase in the influence of the cormorants, while the concentrations of Rb and Pb decreased. The concentrations of Mn differed between zones, but were not related to the intensity of bird influence. Differences in the concentration of Zn (ANOVA F = 24.38; p < 0.001), Fe (F = 4.60; p < 0.05) and Mo (F = 4.47; p < 0.05) were related to the gender factor, all concentrations being higher in females. The concentrations of Zn were age-dependent, being highest in adult individuals (21.7 ± 4.5 μg g[-1]) and exceeding those in subadult (19.4 ± 3.4 μg g[-1]) individuals or juveniles (16.7 ± 1.3 μg g[-1]). In general, the concentrations of accumulated elements in A. flavicollis from the territory of the cormorant colony were lower than in rodents from industrially polluted sites.}, } @article {pmid30214941, year = {2018}, author = {Almaraz, M and Bai, E and Wang, C and Trousdell, J and Conley, S and Faloona, I and Houlton, BZ}, title = {Extrapolation of point measurements and fertilizer-only emission factors cannot capture statewide soil NO x emissions.}, journal = {Science advances}, volume = {4}, number = {9}, pages = {eaau7373}, pmid = {30214941}, issn = {2375-2548}, abstract = {Maaz et al. argue that inconsistencies across scales of observation undermine our working hypothesis that soil NO x emissions have been substantially overlooked in California; however, the core issues they raise are already discussed in our manuscript. We agree that point measurements cannot be reliably used to estimate statewide soil NO x emissions-the principal motivation behind our new modeling/airplane approach. Maaz et al.'s presentation of fertilizer-based emission factors (a nonmechanistic scaling of point measures to regions based solely on estimated nitrogen fertilizer application rates) includes no data from California or other semiarid sites, and does not explicitly account for widely known controls of climate, soil, and moisture on soil NO x fluxes. In contrast, our model includes all of these factors. Finally, the fertilizer sales data that Maaz et al. highlight are known to suffer from serious errors and do not offer a logically more robust pathway for spatial analysis of NO x emissions from soil.}, } @article {pmid30214822, year = {2018}, author = {Chudyk, AM and Waldman, C and Horrill, T and Demczuk, L and Shimmin, C and Stoddard, R and Hickes, S and Schultz, ASH}, title = {Models and frameworks of patient engagement in health services research: a scoping review protocol.}, journal = {Research involvement and engagement}, volume = {4}, number = {}, pages = {28}, pmid = {30214822}, issn = {2056-7529}, abstract = {PLAIN ENGLISH SUMMARY: Patient engagement in research is an emerging approach that involves active and meaningful collaboration between researchers and patients throughout all phases of a project, including planning, data collection and analysis, and sharing of findings. To better understand the core features (elements) that underlie patient engagement, it is useful to have a look at models and frameworks that guide its conduct. Therefore, this manuscript aims to present a protocol for a scoping review of models and frameworks of patient engagement in health services research. Methods: Our protocol design is based on an established framework for conducting scoping reviews. We will identify relevant models and frameworks through systematic searches of electronic databases, websites, reference lists of included articles, and correspondence with colleagues and experts. We will include published and unpublished articles that present models and frameworks of patient engagement in health services research and exclude those not in English or unavailable as full texts. Two reviewers will independently review abstracts and full texts of identified articles for inclusion and extract relevant data; a third reviewer will resolve discrepancies. Our primary objective is to count and describe elements of patient engagement that overlap (present in 2 or more) and diverge among included models and frameworks. Discussion: We hope this review will raise awareness of existing models and frameworks of patient engagement in health services research. Further, by identifying elements that overlap and diverge between models and frameworks, this review will contribute to a clearer understanding of what patient engagement in research is and/or could be.

ABSTRACT: Background: Patients can bring an expert voice to healthcare research through their lived experience of receiving healthcare services. Patient engagement in research is an emerging approach that challenges researchers to acknowledge and utilize this expertise through meaningful and active collaboration with patients throughout the research process. In order to facilitate a clearer understanding of the core elements that underlie patient engagement, it is useful to examine existing models and frameworks that guide its conduct. Therefore, the aim of this manuscript is to present a protocol for a scoping review of models and frameworks of patient engagement in health services research. Methods: Drawing on Arksey and O'Malley's and Levac et al.'s framework for scoping reviews, we designed our protocol to identify relevant a) published articles through systematic searches of 7 electronic databases and snowball sampling and b) unpublished articles through systematic searches of databases and websites and snowball sampling. We will include published and unpublished models and frameworks of patient engagement in health services research and exclude those not in English or unavailable as full texts. Two reviewers will independently screen the abstracts and full texts of identified articles for inclusion and extract relevant data; a third reviewer will resolve disagreements. We will conduct a descriptive analysis of the characteristics (i.e., elements underlying patient engagement and those related to the study authors, publication, and model/framework) of included articles and a narrative analysis of the data concerning elements of the model or framework. Our primary objective is to count and describe elements of patient engagement that overlap (present in ≥ 2) and diverge (present in < 2) among identified models and frameworks. Discussion: Through identification of elements that overlap and diverge between existing models and frameworks, this review will provide a starting point for the critical reflection on our collective understanding of what patient engagement in health services research is and/or could be. Ultimately, we hope that the findings of this review raise awareness of existing models and frameworks and shed light on some of the complexity of conducting patient engaged research through identification of key elements that shape this approach.}, } @article {pmid30202430, year = {2018}, author = {Sauvé, G and Bastien, MF and Roy-Gelencser, C and El-Baalbaki, G}, title = {L-carnosine as an enhancer to computerized cognitive behaviour therapy in Japanese workers, an unjustified claim.}, journal = {BioPsychoSocial medicine}, volume = {12}, number = {}, pages = {11}, pmid = {30202430}, issn = {1751-0759}, abstract = {This letter comments on the conclusion drawn by Shirotsuki et al. (2017) in their article entitled "The effect for Japanese workers of a self-help computerized cognitive behaviour therapy program with a supplement soft drink", recently published in BioPsychoSocial Medicine. The authors concluded that their drink, containing L-carnosine, enhances the effects of a computerized cognitive-behavioural therapy (CCBT) on the psychological well-being of healthy Japanese workers. Yet, we argue that their conclusion is unfounded given their results and the methodological shortcomings of their study. Briefly, while the authors reported improvement on the tension-anxiety subscale of the Profile of Mood States (POMS) in the CCBT only group, they also observed a lack of improvement on this subscale in the CCBT+L-carnosine group suggesting that the drink washes out this beneficial effect of CCBT. Methodological issues include the uncontrolled levels of L-carnosine metabolized by participants jeopardize the study's internal validity. Also, the clinical meaningfulness of the findings seems dubious as post-treatment scores remained within the range of the general Japanese population. Consequently, we argue that Shirotsuki et al.'s study should be re-conducted before drawing any valid conclusion.}, } @article {pmid30188615, year = {2018}, author = {Cope, AL and Butt, KG and Chestnutt, IG}, title = {Why might patients in the UK consult a general medical practitioner when experiencing dental problems? A literature review of patients' perspectives.}, journal = {Community dental health}, volume = {35}, number = {4}, pages = {235-240}, doi = {10.1922/CDH_4369Cope06}, pmid = {30188615}, issn = {0265-539X}, mesh = {Adult ; Child ; *Delivery of Health Care ; *Dental Care ; Humans ; Oral Health ; Qualitative Research ; *Referral and Consultation ; United Kingdom ; }, abstract = {OBJECTIVE: to systematically appraise and synthesise the existing evidence regarding the reasons why patients in the UK may consult a general medical practitioner (GMP) when experiencing a dental problem.

BASIC RESEARCH DESIGN: a systematic review of the scientific and grey literature published between 1996 and 2017.

PARTICIPANTS: dental service users (adults or children) from the UK and/or their carers who were seeking, or had sought, care for a dental problem from a GMP.

MAIN OUTCOMES: patients' perspectives on reasons for consulting a GMP were qualitatively synthesised according to Levesque et al.'s conceptual framework of access to health care.

RESULTS: Out of 1,232 references screened, 2 studies met the inclusion criteria for the review. They identified the following factors that can influence care-seeking for dental problems: patients' interpretation of their symptoms; their understanding of practitioners' scope of practice; the availability of timely dental care; and the affordability of care. Both studies had weaknesses with regard to either their conduct and/or reporting.

CONCLUSIONS: Choice of practitioner for dental problems is likely to be influenced by both the beliefs and attitudes of the individual patient and the organisation and attributes of the providers of dental and medical care. However, in light of the quality of the existing evidence base, there is a need for high-quality studies exploring the reasons why patients in the UK may seek care from a GMP when experiencing dental problems.}, } @article {pmid30188168, year = {2018}, author = {Syed, M and Santos, C and Yoo, HC and Juang, LP}, title = {Invisibility of racial/ethnic minorities in developmental science: Implications for research and institutional practices.}, journal = {The American psychologist}, volume = {73}, number = {6}, pages = {812-826}, doi = {10.1037/amp0000294}, pmid = {30188168}, issn = {1935-990X}, mesh = {Humans ; Institutional Practice ; *Minority Groups ; *Psychology, Developmental ; *Research ; }, abstract = {García Coll et al.'s (1996) integrative model was a landmark article for developmental science, and for psychology more broadly, in outlining the multitude of social and cultural factors at play when seeking to understand the development of racial/ethnic minority children. The time is ripe to not only take stock of those advances but also evaluate the integrative model in the context of present-day research practice within developmental psychology, and psychology more broadly. The purpose of this article is to bring a systemic perspective to developmental science through a discussion of current practices in the field. To do so, we examine invisibility, or how dominant practices serve to overlook, silence, or dismiss knowledge produced by and for racial/ethnic minority populations. Guided by the interpretive framework of intersectionality (Crenshaw, 1991), we discuss three key questions: From whose vantage point is research conducted? What types of questions are valued? And who gets left out? We then conclude with recommendations for changes in practices for individuals, institutions, and the field at large. Importantly, although our analysis is largely grounded in research and practices in developmental psychology, it is also highly relevant to psychological science as a whole. (PsycINFO Database Record}, } @article {pmid30188167, year = {2018}, author = {Juang, LP and Simpson, JA and Lee, RM and Rothman, AJ and Titzmann, PF and Schachner, MK and Korn, L and Heinemeier, D and Betsch, C}, title = {Using attachment and relational perspectives to understand adaptation and resilience among immigrant and refugee youth.}, journal = {The American psychologist}, volume = {73}, number = {6}, pages = {797-811}, doi = {10.1037/amp0000286}, pmid = {30188167}, issn = {1935-990X}, support = {//Foreign Office of the Federal Republic of Germany/International ; }, mesh = {Adaptation, Psychological/*physiology ; Adolescent ; Child ; Child Development ; Emigrants and Immigrants/*psychology ; Humans ; *Interpersonal Relations ; *Object Attachment ; Peer Group ; Refugees/*psychology ; *Resilience, Psychological ; Schools ; }, abstract = {Migration is a critical issue for child development in the 21st century. We expand on García Coll et al.'s (1996) integrative model of minority child development by drawing from principles of attachment theory and interpersonal relationships research to offer new insights into how youth manage and respond to migration experiences. Immigrant and refugee youth should experience better outcomes to the extent that they (a) maintain strong relationships with caregivers and peers who provide a sense of closeness, safety, and confidence during the process of adjusting to this life transition and (b) find ways to establish a sense of connection and belonging to the new people, places, communities, and social networks within which they now live. Strong bonds to people and connection to places (both familiar and new) can counter the social stratification consequences to minority youth development that are well articulated in García Coll et al.'s integrative model. The need for new and better strategies that promote the positive development of immigrant and refugee youth within their families, schools, workplaces, and communities is crucial, not only for individuals and families but for society as a whole. (PsycINFO Database Record}, } @article {pmid30188166, year = {2018}, author = {Suárez-Orozco, C and Motti-Stefanidi, F and Marks, A and Katsiaficas, D}, title = {An integrative risk and resilience model for understanding the adaptation of immigrant-origin children and youth.}, journal = {The American psychologist}, volume = {73}, number = {6}, pages = {781-796}, doi = {10.1037/amp0000265}, pmid = {30188166}, issn = {1935-990X}, mesh = {Adaptation, Psychological/*physiology ; Adolescent ; Child ; Emigrants and Immigrants/*psychology ; Humans ; *Models, Psychological ; Refugees/*psychology ; *Resilience, Psychological ; Stress, Psychological/*psychology ; }, abstract = {We propose an integrative model for the adaptation of immigrant-origin children and youth that combines ecological with risk and resilience frameworks. Immigrant-origin children and youth are now, and will continue to be, a diverse and demographically important segment of all postindustrial nations' populations. Synthesizing evidence across psychological, educational, and sociological disciplines produced since the seminal publication of García Coll et al.'s (1996) model, along with significant events such as a global refugee crisis, a sociopolitical "deportation nation" climate, and heightened xenophobia, we provide a model for understanding the current conditions immigrant-origin children and youth encounter as they develop. This new integrative conceptual model for addressing positive frameworks for adaptation provides a culturally relevant approach for understanding both the risks and resilience of this population. The model was designed to inform practice and future research in the service of immigrant-origin children and youth. (PsycINFO Database Record}, } @article {pmid30188021, year = {2018}, author = {Fox, A and O'Keefe, M and Lanigan, B}, title = {A follow-on study on vision-related quality of life assessment using the NEI-VFQ-25 in those with a history of unilateral and bilateral congenital cataracts.}, journal = {Acta ophthalmologica}, volume = {96}, number = {5}, pages = {e596-e599}, doi = {10.1111/aos.13692}, pmid = {30188021}, issn = {1755-3768}, mesh = {Adolescent ; Adult ; Cataract/*congenital/diagnosis/psychology ; *Cataract Extraction ; Child ; Child, Preschool ; Female ; Follow-Up Studies ; *Health Status ; Humans ; Infant ; Male ; *Patient Education as Topic ; *Quality of Life ; Retrospective Studies ; *Surveys and Questionnaires ; Time Factors ; Visual Acuity/*physiology ; Young Adult ; }, abstract = {PURPOSE: To assess vision-specific health-related quality of life (using the NEI-VFQ-25), educational attainment and visual acuity (VA) in patients with a history of congenital cataracts and appraise these in relation to Kirwan et al.'s (Pediatr Ophthalmol Strabismus 49, 2012, 26) study.

METHODS: A retrospective hospital-based study of patients with unilateral and bilateral congenital cataracts whounderwent surgery aged younger than 12 months. Those 13 years or older at follow-up were selected for inclusion. Patients with glaucoma, other associated ocular complications or systemic abnormalities were excluded. Educational attainment and VA at latest review were recorded.

RESULTS: Twelve patients with unilateral cataract (mean age: 26 ± 4.5) and fifteen with bilateral cataract (mean age 22 ± 4.3) were included. Bilateral group had greater difficulty with near and distance activities, vision-specific role difficulties, vision-specific dependency and general health than the unilateral group. There were no significant differences with regard to ocular pain, vision-specific social functioning, vision-specific mental health, driving, colour vision, peripheral vision or educational attainment between the groups. All patients attended mainstream school, and majority progressed to third-level education. Follow up at an increased time from surgery - 6.2 ± 5.13 (unilateral) and 6.5 ± 6.4 years (bilateral) - compared to Kirwan et al.'s study.

CONCLUSION: Results were in keeping with Kirwan et al.'s. Bilateral group had greater difficulty with day-to-day tasks compared to the unilateral group, including near and distance vision activities. They had greater vision-specific role difficulties and vision-specific dependency. There was no difference between the groups in regard to vision-specific social functioning, vision-specific mental health or educational attainment. This can be a source of reassurance to parents and patients.}, } @article {pmid30184283, year = {2019}, author = {Gilmore-Bykovskyi, A and Block, L and Johnson, R and Goris, ED}, title = {Symptoms of apathy and passivity in dementia: A simultaneous concept analysis.}, journal = {Journal of clinical nursing}, volume = {28}, number = {3-4}, pages = {410-419}, pmid = {30184283}, issn = {1365-2702}, support = {//National Institute on Aging/ ; //Kenneth H. Campbell Foundation for Neurological Research/ ; //Wisconsin Alzheimer's Disease Research Center/ ; P50 AG033514/AG/NIA NIH HHS/United States ; //National Hartford Centers of Gerontological Nursing Excellence/ ; }, mesh = {*Apathy ; Dementia/*psychology ; Humans ; }, abstract = {AIMS AND OBJECTIVES: The objective of this analysis was to clarify the concepts of apathy and passivity in the context of dementia by identifying distinguishing and overlapping attributes for both concepts simultaneously.

BACKGROUND: Apathy is among the most common and persistent symptoms in dementia. The concept of apathy is often used interchangeably with passivity. Understanding similarities and differences between these concepts is of critical importance in clarifying clinical diagnostic criteria, developing consistent measurement in research and translating research evidence into nursing practice.

DESIGN: A systematic literature search of multiple databases identified relevant articles for review. A modified combination of Haase et al.'s simultaneous concept analysis method and Morses' principle-based concept analysis using qualitative content and thematic analysis procedures was applied to identify overlapping and distinguishing attributes.

METHODS: A search of PubMed, CINAHL and PsycINFO databases identified 176 articles meeting inclusion criteria. The concepts of apathy and passivity were characterised using a standardised manual to identify attributes of definitions (conceptual and operational), related conditions, functional, behavioural and neurobiological correlates, antecedents and consequences. Thematic analysis identified common themes across each category which were tabulated and entered into comparative matrices to identify overlapping and distinguishing features.

RESULTS: There is considerable overlap across attributes of apathy and passivity. Apathy is distinguished as a clinical syndrome characterised by loss of motivation not due to emotional distress or cognitive impairment. Passivity is distinguished as a lack of interaction between the individual and environment in the context of cognitive impairment.

CONCLUSION: In contrast to passivity, apathy is a more robustly defined concept focused on motivational limitations within the individual associated with specific neuroanatomical deficits.

The identification of key distinguishing features of apathy and passivity in dementia is a critical first step in ensuring consistent measurement of each concept.}, } @article {pmid30179036, year = {2018}, author = {Saint-Aubin, J and Hilchey, MD and Mishra, R and Singh, N and Savoie, D and Guitard, D and Klein, RM}, title = {Does the relation between the control of attention and second language proficiency generalize from India to Canada?.}, journal = {Canadian journal of experimental psychology = Revue canadienne de psychologie experimentale}, volume = {72}, number = {3}, pages = {208-218}, doi = {10.1037/cep0000151}, pmid = {30179036}, issn = {1878-7290}, mesh = {Adolescent ; Adult ; Attention/*physiology ; Canada ; Executive Function/*physiology ; Humans ; India ; *Multilingualism ; Psychomotor Performance/*physiology ; Young Adult ; }, abstract = {Over the last decades, the extralinguistic benefits of bilingualism have been intensively debated. The current study was aimed at clarifying whether bilingualism speeds attentional disengagement. Reflecting faster disengagement, Mishra, Hilchey, Singh, and Klein (2012) observed an earlier onset of inhibition of return (IOR) for high than for low-proficient bilinguals. In contrast, Hernandez, Costa, Fuentes, Vivas, and Sebastian-Galles (2010) failed to find any difference between bilinguals and monolinguals. We investigated the source of this discrepancy, while improving methodology by using a large sample composed of 100 Canadians, objective assessments of second language skills (Nelson-Denny Reading test), and controlling for nonverbal intelligence, age, sex, and video-gaming. Results were analyzed with self-report and objective measures of second language proficiency as well as dichotomous and continuous measures. Compared to less proficient bilinguals, highly proficient bilinguals tended to respond faster overall, hinting at an executive processing advantage. However, contrary to Mishra et al.'s findings, bilingual proficiency did not affect either the onset of IOR or magnitude of IOR. (PsycINFO Database Record}, } @article {pmid30175532, year = {2019}, author = {McKinlay, E and McDonald, J and Darlow, B and Perry, M}, title = {The social networks of New Zealand patients with multimorbidity and the work of those nominated as their 'significant supporters': An exploratory study.}, journal = {Health & social care in the community}, volume = {27}, number = {2}, pages = {392-399}, doi = {10.1111/hsc.12657}, pmid = {30175532}, issn = {1365-2524}, support = {//Centre for Interprofessional Education, University of Otago/International ; }, mesh = {Adult ; Chronic Disease/*epidemiology ; Community Health Services/*methods ; Female ; General Practice ; Humans ; Male ; Middle Aged ; *Multimorbidity ; New Zealand ; Social Networking ; Social Support ; }, abstract = {Social networks are informal relationships often with social ties and voluntary or mandatory obligations that can positively support a patient with multimorbidity. This exploratory study sought insights into the social networks of New Zealand people with multimorbidity and also the work of those nominated as providing significant support. Ten participants were recruited from general practice as part of an education programme in which health professional students discussed living with multimorbidity and completed a social network template together with patients. Each patient nominated an individual from their social network whom they considered provided significant support. A researcher interviewed each supporter about their experience of providing support, and their view of the patient's social network. Significant supporters included three classified as 'lay' supporters (sister, wife and daughter) and seven classified as 'professional' supporters (exercise physiologist, general practitioners, nurse, medical specialists). The activities described by supporters was classified according to Vassilev et al.'s expansion of Corbin and Strauss's 1985 classification of work in chronic illness, including the categories of "illness," "everyday" and "emotional" work. Irrespective of whether supporters were lay or professional, they gave examples of each category. While this is expected of lay supporters, it is not expected of professional supporters who are typically viewed as undertaking illness work. Lay supporters described a complex array of activities sometimes impacting on their own personal well-being, making them more akin to meeting the formal definition of being a carer, while professional supports gave objective yet professionally invested descriptions. The work of lay and professional supporters is complementary in the provision of support for those with multimorbidity. Consideration should be given to the role of lay supporters and to their own needs if they are to be able to sustain their support work with patients.}, } @article {pmid30165336, year = {2018}, author = {Stupak, HD and Park, SY}, title = {Gravitational forces, negative pressure and facial structure in the genesis of airway dysfunction during sleep: a review of the paradigm.}, journal = {Sleep medicine}, volume = {51}, number = {}, pages = {125-132}, doi = {10.1016/j.sleep.2018.06.016}, pmid = {30165336}, issn = {1878-5506}, mesh = {Adenoidectomy/adverse effects/methods ; Airway Obstruction/*complications ; Face ; Humans ; Mouth Breathing/*etiology ; Sleep Apnea, Obstructive/*complications/etiology ; Tonsillectomy/adverse effects/methods ; }, abstract = {The recent and distant literature has extensive discussion of how sleep apnea, adeno-tonsillar growth, and facial structural deformity are related. Conventionally, the order of cause and effect is as follows: (1) Inflammatory/infectious process→tonsillar/adenoid tissue growth→(2) airway obstruction and mouth breathing/Obstructive Sleep Apnea (OSA)→(3) altered facial structure (adenoid facies). Using this same reasoning, adenotonsillectomy is the first line of treatment in the prevention of structural abnormalities. However, through a lifetime of clinical research Christian Guilleminault and his colleagues have challenged this paradigm. Through multiple articles and studies, Guilleminault et al., teach that even slight (subclinical) facial structure/muscle tone variations may be the inciting event triggering mouth-breathing and the eventual adenotonsillar growth in most patients. Essentially, this is the reverse of the conventional paradigms. Initial treatments therefore shift from simplified removal of inflammatory tissue to limiting mouth-breathing via musculo-skeletal modification. The purpose of this paper is to synthesize and analyze the recent (and distant) relevant literature to provide support for, and provide a potential anatomic mechanism for Guilleminault et al.'s paradigm-questioning clinical observations.}, } @article {pmid30155355, year = {2018}, author = {Gao, Y and Melin, M and Mäkäräinen, K and Rantalainen, T and Pesola, AJ and Laukkanen, A and Sääkslahti, A and Finni, T}, title = {Children's physical activity and sedentary time compared using assessments of accelerometry counts and muscle activity level.}, journal = {PeerJ}, volume = {6}, number = {}, pages = {e5437}, pmid = {30155355}, issn = {2167-8359}, abstract = {BACKGROUND: This research compared accelerometry (ACC)-derived and muscle electromyography (EMG)-based estimates of physical activity (PA) and sedentary time in typical PA tasks and during the daily lives of children.

METHODS: Data was included from two exploratory studies. In Study I, 6-7-year-old children (n = 11, 64% girls) were assessed for eight PA tasks (walking, stair negotiation, climbing, crawling, swinging, balancing, trampoline jumping and a game of tag). In Study II, 7-9-year-old children (n = 14, 38% girls) were assessed for six PA tasks (walking, sitting, static squat, single leg hops, jump for height and standing long jump), and daily PA during one day with and one day without structured exercise. Quadriceps and hamstring muscle activity and inactivity using EMG shorts and acceleration by waist-mounted accelerometer were simultaneously measured and classified as sedentary, light, moderate and vigorous activity. Data from ACC was further analyzed using five different published cut-off points and varying time windows (1-60 s) for comparison with EMG.

RESULTS: In the PA tasks ACC counts and EMG amplitude showed marked differences in swinging, trampoline jumping, crawling, static squat, single leg hops, standing long jump and jump for height, the difference being over 170% when signals were normalized to that during walking. Furthermore, in walking, swinging, trampoline jumping, stair negotiation and crawling ACC classified over 60% of the time as vigorous-intensity activity, while EMG indicated primarily light- and moderate-intensity activities. During both days with and without exercise, ACC resulted in greater proportion of light activity (p < 0.01) and smaller proportion of moderate activity compared to EMG (p < 0.05). The choice of cut-off points and epoch length in ACC analysis influenced the classification of PA level and sedentary time. In the analysis of daily activities the cut-off points by Evenson et al. (2008) with epochs of 7.5 s and 15 s yielded the smallest difference (less than 10% of recording time at each intensity) against EMG-derived PA levels.

DISCUSSION: This research provides novel insight on muscle activity and thereby on neuromuscular loading of major locomotor muscles during normal daily activities of children. While EMG and ACC provided similar estimates of sedentary time in 13 typical PA tasks, duration of light, moderate and vigorous PA varied considerably between the methods especially during walking, stair negotiation, crawling, swinging and trampoline jumping. Evenson et al.'s (2008) cut-off points with ≤15 s epoch provided similar classification of PA than EMG during daily life. Compared to impacts recorded using ACC, EMG can provide understanding on children's neuromuscular loading during motor tasks that is useful when studying effects of PA interventions on, and development of, motor competence and coordination.}, } @article {pmid30147205, year = {2018}, author = {Leydesdorff, L}, title = {Diversity and interdisciplinarity: how can one distinguish and recombine disparity, variety, and balance?.}, journal = {Scientometrics}, volume = {116}, number = {3}, pages = {2113-2121}, pmid = {30147205}, issn = {0138-9130}, abstract = {The dilemma which remained unsolved using Rao-Stirling diversity, namely of how variety and balance can be combined into "dual concept diversity" (Stirling in SPRU electronic working paper series no. 28. http://www.sussex.ac.uk/Units/spru/publications/imprint/sewps/sewp28/sewp28.pdf, 1998, p. 48f.) can be clarified by using Nijssen et al.'s (Coenoses 13(1):33-38 1998) argument that the Gini coefficient is a perfect indicator of balance. However, the Gini coefficient is not an indicator of variety; this latter term can be operationalized independently as relative variety. The three components of diversity-variety, balance, and disparity-can thus be clearly distinguished and independently operationalized as measures varying between zero and one. The new diversity indicator ranges with more resolving power in the empirical case.}, } @article {pmid30147154, year = {2018}, author = {Bell, A and Jones, K and Fairbrother, M}, title = {Understanding and misunderstanding group mean centering: a commentary on Kelley et al.'s dangerous practice.}, journal = {Quality & quantity}, volume = {52}, number = {5}, pages = {2031-2036}, pmid = {30147154}, issn = {0033-5177}, abstract = {Kelley et al. argue that group-mean-centering covariates in multilevel models is dangerous, since-they claim-it generates results that are biased and misleading. We argue instead that what is dangerous is Kelley et al.'s unjustified assault on a simple statistical procedure that is enormously helpful, if not vital, in analyses of multilevel data. Kelley et al.'s arguments appear to be based on a faulty algebraic operation, and on a simplistic argument that parameter estimates from models with mean-centered covariates must be wrong merely because they are different than those from models with uncentered covariates. They also fail to explain why researchers should dispense with mean-centering when it is central to the estimation of fixed effects models-a common alternative approach to the analysis of clustered data, albeit one increasingly incorporated within a random effects framework. Group-mean-centering is, in short, no more dangerous than any other statistical procedure, and should remain a normal part of multilevel data analyses where it can be judiciously employed to good effect.}, } @article {pmid30146716, year = {2018}, author = {Tibayrenc, M and Ayala, F}, title = {Hybridization in Trypanosoma congolense does not challenge the predominant clonal evolution model. A comment on Tihon et al., 2017, Mol. Ecol.}, journal = {Molecular ecology}, volume = {27}, number = {17}, pages = {3421-3424}, doi = {10.1111/mec.14714}, pmid = {30146716}, issn = {1365-294X}, mesh = {Animals ; Clonal Evolution ; Genomics ; *Trypanosoma congolense ; *Trypanosomiasis, African ; Zambia ; }, abstract = {Tihon et al. have just published in Mol. Ecol. a fine genomic study on Trypanosoma congolense, agent of Animal African Trypanosomiasis. They present very convincing evidence that T. congolense underwent several hybridization events between distinct genetic lines in Zambia. They claim that their data challenge our predominant clonal evolution model (PCE) of micropathogens. We point out the main tenets of our model and show that Tihon et al.'s claim is based on a misinterpretation of the PCE model. Actually, their data strongly support PCE in T. congolense at a microevolutionary level.}, } @article {pmid30142002, year = {2019}, author = {Agarwal, A and Invernizzi, A and Jain, S and Acquistapace, A and Riva, A and Sharma, A and Gupta, V and Singh, R}, title = {Choroidal Thickness in Patients Diagnosed with Human Immunodeficiency Virus Infection: Results from Two Populations of Different Ethnicities: Response to Chay et al.'s Letter.}, journal = {Ocular immunology and inflammation}, volume = {27}, number = {4}, pages = {569-570}, doi = {10.1080/09273948.2018.1508730}, pmid = {30142002}, issn = {1744-5078}, mesh = {Choroid ; Ethnicity ; HIV ; HIV Infections/*virology ; Humans ; }, } @article {pmid30132437, year = {2018}, author = {Delisle Nyström, C and Söderström, E and Henriksson, P and Henriksson, H and Poortvliet, E and Löf, M}, title = {The paediatric option for BodPod to assess body composition in preschool children: what fat-free mass density values should be used?.}, journal = {The British journal of nutrition}, volume = {120}, number = {7}, pages = {797-802}, doi = {10.1017/S0007114518002064}, pmid = {30132437}, issn = {1475-2662}, mesh = {Adipose Tissue/*metabolism ; *Body Composition ; Body Fluid Compartments/*metabolism ; Child, Preschool ; Female ; Humans ; Male ; Pediatrics/*methods ; Plethysmography/methods ; Reference Values ; Sweden ; }, abstract = {Air displacement plethysmography utilises a two-component model to assess body composition, which relies on assumptions regarding the density of fat-free mass (FFM). To date, there is no evidence as to whether Lohman's or Wells et al.'s FFM density values are more accurate in young children. Therefore, the aims of this study were to compare total body fat percentage (TBF%) assessed using the BodPod with both Lohman's and Wells et al.'s FFM density values with TBF% from the three-component (3C) model in forty healthy Swedish children aged 5·5 years. Average TBF% calculated using Lohman's FFM density values underestimated TBF% in comparison with the corresponding value assessed using the 3C model (22·2 (sd 5·7) and 25·1 (sd 5·5) %, respectively; P<0·001). No statistically significant difference was observed between TBF% assessed using Wells et al.'s FFM density values and the 3C model (24·9 (sd 5·5) and 25·1 (sd 5·5) %, respectively; P=0·614). The Bland and Altman plots for TBF% using both Lohman's and Wells et al.'s FFM density values did not show any bias across the range of body fatness (Lohman: r 0·056, P=0·733 and Wells et al.: r -0·006, P=0·970). These results indicate that Wells et al.'s FFM density values should be used when assessing body composition with the paediatric option for BodPod in 5-year-old children. However, future studies are needed to confirm these results in other populations, including a wider age range of children.}, } @article {pmid30131626, year = {2018}, author = {Shilpa, BS and Vasudevan, SD and Bhongade, ML and Baliga, V and Pakhare, VV and Dhadse, PV}, title = {Evaluation of survival of 8 mm-length implants in posterior resorbed ridges: A pilot study.}, journal = {Journal of Indian Society of Periodontology}, volume = {22}, number = {4}, pages = {334-339}, pmid = {30131626}, issn = {0972-124X}, abstract = {CONTEXT: Rehabilitation of jaws with reduced bone height is technically demanding and expensive. Short implants are emerging as an alternate in such cases.

AIM: This study aimed to evaluate the survival of implants of 8 mm in length (short implants), clinically and radiographically, in posterior resorbed ridges.

MATERIALS AND METHODS: A total of 11 patients with single missing posterior tooth, having 9-10 mm of residual bone height determined using radiographs, were selected for the study. Twelve implants of 8 mm length were inserted in the resorbed alveolar ridges following standard operating procedure. A second-stage surgery was performed 4-6 months after implant placement for placement of gingival former. This was followed by placement of prosthesis. Twelve months after prosthesis placement, all the patients were examined clinically and radiographically.

RESULTS: According to Albrektsson et al.'s criteria, all implants were successful with mean bone loss of 1.1 ± 0.32 mm mesially and 0.83 ± 0.35 mm distally with healthy gingival condition at 12-month follow-up.

CONCLUSION: Short implants (8 mm in length) can be a viable alternative in cases of atrophic alveolar ridges.}, } @article {pmid30121617, year = {2018}, author = {Brown, J and Goodridge, D and Thorpe, L and Chipanshi, M}, title = {Factors contributing to practitioner choice when declining involvement in legally available care: A scoping protocol.}, journal = {BMJ open}, volume = {8}, number = {8}, pages = {e023901}, pmid = {30121617}, issn = {2044-6055}, mesh = {*Choice Behavior ; *Conscientious Refusal to Treat ; Humans ; Physicians/*psychology/statistics & numerical data ; Scoping Reviews As Topic ; }, abstract = {INTRODUCTION: As legislation addressing medical treatments continues to evolve, there are several circumstances (eg, abortion, assisted dying) in which health practitioners may choose to not provide legally available care options. It is not always clear what underlies practitioner choice, as some research has suggested non-participation in care provision is not always due to an ethical abstention but may represent other factors. This results in tension between a practitioner's right to refrain from practices deemed morally objectionable by the practitioner, and the care recipient's right to access legally available treatments. The aim of this systematic scoping review is to identify the current knowledge regarding all the factors influencing practitioner's choices when declining involvement in legally available healthcare options.

METHODS AND ANALYSIS: Arksey and O'Malley's scoping framework in concert with Levac et al 's enhancements will guide the systematic scoping review methodological processes. English language documents from 1 January 1998 to current will be sought using Medline, CINAHL, JSTOR, EMBASE, ProQuest Dissertations and Theses Global, PsychINFO and Sociological Abstracts. MeSH headings, keywords and synonyms will be adjusted using an iterative search process. Theses and dissertations will be included in the search protocol; however, other grey literature will be accessed only as required. Two research team members will screen the abstracts and full articles against inclusion criteria. Article information will be extracted via a data collection tool and undergo thematic analysis. Descriptive summary (visual summary and study contextual information) and a presentation of analytical themes will align findings back to the research question.

ETHICS AND DISSEMINATION: Ethics approval is not required. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist will be used to support transparency and guide translation of findings. Findings will be disseminated through professional networks, in peer-reviewed journals and conferences via abstract and presentation.}, } @article {pmid30102419, year = {2019}, author = {Golinkoff, RM and Hoff, E and Rowe, ML and Tamis-LeMonda, CS and Hirsh-Pasek, K}, title = {Language Matters: Denying the Existence of the 30-Million-Word Gap Has Serious Consequences.}, journal = {Child development}, volume = {90}, number = {3}, pages = {985-992}, pmid = {30102419}, issn = {1467-8624}, support = {R01 HD068421/HD/NICHD NIH HHS/United States ; }, mesh = {Child ; Humans ; *Language ; *Language Development ; Learning ; Poverty ; Speech ; }, abstract = {Sperry, Sperry, and Miller (2018) aim to debunk what is called the 30-million-word gap by claiming that children from lower income households hear more speech than Hart and Risley () reported. We address why the 30-million-word gap should not be abandoned, and the importance of retaining focus on the vital ingredient to language learning-quality speech directed to children rather than overheard speech, the focus of Sperry et al.'s argument. Three issues are addressed: Whether there is a language gap; the characteristics of speech that promote language development; and the importance of language in school achievement. There are serious risks to claims that low-income children, on average, hear sufficient, high-quality language relative to peers from higher income homes.}, } @article {pmid30085785, year = {2018}, author = {Miao, H and Zhang, TT and Wang, L and Meyers, D and Said, AH and Wang, YL and Shi, YG and Weng, HM and Fang, Z and Dean, MPM}, title = {Observation of Double Weyl Phonons in Parity-Breaking FeSi.}, journal = {Physical review letters}, volume = {121}, number = {3}, pages = {035302}, doi = {10.1103/PhysRevLett.121.035302}, pmid = {30085785}, issn = {1079-7114}, abstract = {Condensed matter systems have now become a fertile ground to discover emerging topological quasiparticles with symmetry protected modes. While many studies have focused on fermionic excitations, the same conceptual framework can also be applied to bosons yielding new types of topological states. Motivated by Zhang et al.'s recent theoretical prediction of double Weyl phonons in transition metal monosilicides [Phys. Rev. Lett. 120, 016401 (2018)PRLTAO0031-900710.1103/PhysRevLett.120.016401], we directly measure the phonon dispersion in parity-breaking FeSi using inelastic x-ray scattering. By comparing the experimental data with theoretical calculations, we make the first observation of double Weyl points in FeSi, which will be an ideal material to explore emerging bosonic excitations and its topologically nontrivial properties.}, } @article {pmid30080085, year = {2018}, author = {LaCroix, JM and Perera, KU and Neely, LL and Grammer, G and Weaver, J and Ghahramanlou-Holloway, M}, title = {Pilot trial of post-admission cognitive therapy: Inpatient program for suicide prevention.}, journal = {Psychological services}, volume = {15}, number = {3}, pages = {279-288}, doi = {10.1037/ser0000224}, pmid = {30080085}, issn = {1939-148X}, support = {//Office of the Congressionally Directed Medical Research Programs (CD-MRP); Department of Defense (DoD) Post-Traumatic Stress Disorder/Traumatic Brain Injury Research Program (PTSD/TBI)/ ; }, mesh = {Adult ; *Cognitive Behavioral Therapy ; Female ; Humans ; Inpatients/*psychology ; Male ; Military Personnel/*psychology ; Pilot Projects ; Suicidal Ideation ; Suicide/psychology ; Suicide, Attempted/psychology ; Treatment Outcome ; Young Adult ; *Suicide Prevention ; }, abstract = {Suicide remains a significant public health problem for the United States military. Trauma-related diagnoses such as acute stress disorder (ASD) or posttraumatic stress disorder (PTSD) may exacerbate suicide risk, particularly among service members psychiatrically hospitalized following suicide-related events. To date, treatments to address suicide risk and trauma symptomatology among service members within inpatient milieus have been nonexistent. To address this gap, a randomized controlled pilot trial of Post-Admission Cognitive Therapy (PACT) was conducted to evaluate a targeted cognitive-behavioral program among traumatized military personnel (N = 36) hospitalized following a recent suicide attempt. All participants met criteria for ASD or PTSD and were randomly assigned to receive either PACT and enhanced usual care (PACT + EUC) or EUC alone. PACT consisted of six 60- to 90-min individual psychotherapy sessions, adapted from Brown et al.'s (2005) cognitive therapy protocol for suicide prevention. Blinded follow-up assessments were conducted at 1-, 2-, and 3-months postpsychiatric discharge. The primary outcome was days until repeat suicide attempt. Secondary outcomes included depression, hopelessness, suicide ideation, and PTSD symptoms. Participants did not significantly differ in reattempt status. However, based on reliable change index analyses, a greater proportion of PACT + EUC versus EUC participants met criteria for clinically significant change on measures of depression (100% vs. 78%), hopelessness (83% vs. 57%), and PTSD symptom severity (100% vs. 38%), but not for suicide ideation (60% vs. 67%). PACT is an innovative inpatient protocol, currently under evaluation in a well-powered multisite RCT for its efficacy in reducing subsequent suicidal behaviors. (PsycINFO Database Record}, } @article {pmid30080070, year = {2018}, author = {Fragaszy, DM}, title = {Persistent pigeons (Columba livia) learn how to produce a list.}, journal = {Journal of comparative psychology (Washington, D.C. : 1983)}, volume = {132}, number = {3}, pages = {231-233}, doi = {10.1037/com0000141}, pmid = {30080070}, issn = {1939-2087}, mesh = {Animals ; *Attention ; Columbidae ; *Psychology, Comparative ; Retention, Psychology ; *Serial Learning ; Species Specificity ; }, abstract = {In the Featured Article for this issue of the Journal of Comparative Psychology, Scarf, Johnston, and Colombo (2018) showed that pigeons learned to reproduce (by pecking icons presented on a screen) a four-item serially ordered list without specific training on that list, as macaques did (Figure 1). In Scarf et al.'s (2018) study, all five birds given structured training subsequently mastered multiple sets of two-item, then three-item, and finally four-item lists, with a diminishing training regime for the later four-item lists. Scarf et al.'s (2018) findings have at least two important implications for our science: First, members of evolutionarily distant taxa, pigeons and monkeys, can both produce a serially ordered set of four actions. Second, we are reminded that learning sets can be acquired for diverse tasks-the principles of learning set formation are very general. (PsycINFO Database Record}, } @article {pmid30058524, year = {2019}, author = {Munder, T and Flückiger, C and Leichsenring, F and Abbass, AA and Hilsenroth, MJ and Luyten, P and Rabung, S and Steinert, C and Wampold, BE}, title = {Is psychotherapy effective? A re-analysis of treatments for depression.}, journal = {Epidemiology and psychiatric sciences}, volume = {28}, number = {3}, pages = {268-274}, pmid = {30058524}, issn = {2045-7979}, mesh = {Adult ; *Depression ; *Depressive Disorder ; Humans ; Psychotherapy ; Waiting Lists ; }, abstract = {UNLABELLED: AimsThe aim of this study was to reanalyse the data from Cuijpers et al.'s (2018) meta-analysis, to examine Eysenck's claim that psychotherapy is not effective. Cuijpers et al., after correcting for bias, concluded that the effect of psychotherapy for depression was small (standardised mean difference, SMD, between 0.20 and 0.30), providing evidence that psychotherapy is not as effective as generally accepted.

METHODS: The data for this study were the effect sizes included in Cuijpers et al. (2018). We removed outliers from the data set of effects, corrected for publication bias and segregated psychotherapy from other interventions. In our study, we considered wait-list (WL) controls as the most appropriate estimate of the natural history of depression without intervention.

RESULTS: The SMD for all interventions and for psychotherapy compared to WL controls was approximately 0.70, a value consistent with past estimates of the effectiveness of psychotherapy. Psychotherapy was also more effective than care-as-usual (SMD = 0.31) and other control groups (SMD = 0.43).

CONCLUSIONS: The re-analysis reveals that psychotherapy for adult patients diagnosed with depression is effective.}, } @article {pmid30056568, year = {2018}, author = {Schafheutle, EI and Fegan, T and Ashcroft, DM}, title = {Exploring medicines management by COPD patients and their social networks after hospital discharge.}, journal = {International journal of clinical pharmacy}, volume = {40}, number = {5}, pages = {1019-1029}, pmid = {30056568}, issn = {2210-7711}, mesh = {Aged ; Aged, 80 and over ; *Disease Management ; Female ; Health Knowledge, Attitudes, Practice ; Hospitalization/trends ; Humans ; Male ; Middle Aged ; Patient Discharge/*trends ; Pulmonary Disease, Chronic Obstructive/*drug therapy/psychology ; Self Care/methods/*trends ; *Social Networking ; }, abstract = {Background Unplanned hospital admissions (UHAs) for chronic obstructive pulmonary disease (COPD) are a major burden on health services. Effective medicines management is crucial to avoid such admissions but little is known about the role of social networks in supporting medicines-taking. Objective To examine the activities and strategies recently discharged COPD patients and their social network members (SNMs) utilise to manage their medicines. Setting COPD patients recently discharged from an acute NHS Trust in Northwest England. Methods Semi-structured, face-to-face interviews; audio-recorded and transcribed with consent, NVivo v11 facilitated qualitative thematic analysis. NHS ethical approved. Main outcome measure Interview topic guide and analysis informed by Cheraghi-Sohi et al.'s conceptual framework for 'medication work' exploring medication-articulation, informational, emotional and surveillance work. Results Twelve interviews were conducted during March-August 2016. Participants' social networks were small (n < 5) and restricted to family members and healthcare professionals. Participants social network members performed similar medication-articulation and surveillance work to coronary heart disease, arthritis and diabetes patients. When participants social network members resolved issues identified by surveillance work, this medication work was conceptualised as surveillance-articulation work. The social network members performed little emotional work and were infrequently involved in informational work despite some participants describing informational needs. After discharge, participants reverted to pre-admission routines/habits/strategies for obtaining medication supplies, organising medicines, keeping track of supplies, ensuring adherence within daily regimens, and monitoring symptoms, which could cause issues. Conclusion This study applied Cheraghi-Sohi's framework for medication work to COPD patients and described the role of the social network members. Pharmacists could proactively explore medication infrastructures and work with patients and their close social network members to support medication work.}, } @article {pmid30041475, year = {2018}, author = {Xu, G and Qiu, S and Ahmad, H and Xu, G and Guo, Y and Zhang, M and Xu, H}, title = {A Multi-Server Two-Factor Authentication Scheme with Un-Traceability Using Elliptic Curve Cryptography.}, journal = {Sensors (Basel, Switzerland)}, volume = {18}, number = {7}, pages = {}, pmid = {30041475}, issn = {1424-8220}, abstract = {To provide secure communication, the authentication-and-key-agreement scheme plays a vital role in multi-server environments, Internet of Things (IoT), wireless sensor networks (WSNs), etc. This scheme enables users and servers to negotiate for a common session initiation key. Our proposal first analyzes Amin et al.'s authentication scheme based on RSA and proves that it cannot provide perfect forward secrecy and user un-traceability, and is susceptible to offline password guessing attack and key-compromise user impersonation attack. Secondly, we provide that Srinivas et al.'s multi-server authentication scheme is not secured against offline password guessing attack and key-compromise user impersonation attack, and is unable to ensure user un-traceability. To remedy such limitations and improve computational efficiency, we present a multi-server two-factor authentication scheme using elliptic curve cryptography (ECC). Subsequently, employing heuristic analysis and Burrows[-]Abadi[-]Needham logic (BAN-Logic) proof, it is proven that the presented scheme provides security against all known attacks, and in particular provides user un-traceability and perfect forward security. Finally, appropriate comparisons with prevalent works demonstrate the robustness and feasibility of the presented solution in multi-server environments.}, } @article {pmid30039657, year = {2018}, author = {Zhou, JC and Liu, XF and Ji, YH and Zhang, QF and Zheng, Y and Chen, YM and Yang, YS}, title = {[Effects of precipitation reduction on the composition and stability of soil organic matter in a young Cunninghamia lanceolata plantation.].}, journal = {Ying yong sheng tai xue bao = The journal of applied ecology}, volume = {29}, number = {7}, pages = {2203-2210}, doi = {10.13287/j.1001-9332.201807.001}, pmid = {30039657}, issn = {1001-9332}, mesh = {Agriculture ; Carbon ; *Climate Change ; *Cunninghamia ; Lignin ; Rain ; Soil/*chemistry ; }, abstract = {It is hard to predict the response of soil organic matter (SOM) to global climate change due to its heterogenous chemical structure. With the development of molecular techniques to identify the structure, sources and stages of SOM degradation, long-standing questions regarding the composition and stability of SOM might be resolved. To investigate the effects of changes in precipitation patterns on the stability of SOM, we analyzed the specific compositions and extent of degradation of SOM using biomarkers, in a young Cunninghamia lanceolata plantation after reducing 50% of precipitation (P) for two years. The results showed that precipitation reduction (P-treatment) significantly reduced the levels of free lipids. Relative to control (CT), P-treatment decreased short-chain n-alkanoic acids (C16-18) and terpenoids and steroids by 62.8% and 19.1%, respectively. However, P-treatment did not significantly change the concentrations of other aliphatic compounds. Although there was no observable difference in the total lignin content between treatments, P-treatment significantly reduced the acid to aldehyde ratios for syringyl [(Ad/Al)s] and vanillyl [(Ad/Al)v]. Thus, the labile compositions of SOM were accelerated to decomposition under rainfall pattern change. Although the recalcitrant compositions (lignin) were relatively stable, their long-term stability should be further monitored.}, } @article {pmid30033814, year = {2018}, author = {Miozzo, M and Shuster, VP and Fischer-Baum, S}, title = {How modality-specific is morphology?.}, journal = {Cognitive neuropsychology}, volume = {35}, number = {7}, pages = {371-384}, doi = {10.1080/02643294.2018.1491833}, pmid = {30033814}, issn = {1464-0627}, mesh = {Adult ; Aphasia/*physiopathology/*psychology ; Female ; Humans ; Linguistics ; Middle Aged ; Speech/*physiology ; *Writing ; }, abstract = {Writing has long been considered to be dependent on speaking. However, modality-specific dissociations between written and spoken word production imply that word production is supported by distinct neural mechanisms in writing, which can be impaired or spared regardless of the intactness of spoken word production. Rapp et al. (2015). Modality and morphology: What we write may not be what we say. Psychological Science, 26, 892-902 documented a double dissociation where problems with regular inflections were selectively restricted to writing or speaking. We report on two English-speaking aphasic individuals who exhibit this same modality-specific dissociation of inflectional processing, replicating the original findings. We expand on Rapp et al.'s study by examining whether the dissociations observed with regular inflections extend to other morphological forms, such as derivation and irregular inflection. Results showed that the dissociation holds for derivation; however, both participants were impaired with irregular inflections in both output modalities. Implications of these findings for morphological processing and the independence of the orthographic system are discussed.}, } @article {pmid30027567, year = {2019}, author = {Höchenberger, R and Ohla, K}, title = {A bittersweet symphony: Evidence for taste-sound correspondences without effects on taste quality-specific perception.}, journal = {Journal of neuroscience research}, volume = {97}, number = {3}, pages = {267-275}, doi = {10.1002/jnr.24308}, pmid = {30027567}, issn = {1097-4547}, mesh = {Acoustic Stimulation/*psychology ; Adult ; Auditory Perception ; Female ; Food Preferences ; Humans ; Male ; Middle Aged ; Music/*psychology ; *Taste ; *Taste Perception ; }, abstract = {Music has been associated with taste and shown to influence the dining experience. We asked whether sound that is associated with taste affects taste perception of food. In two studies (study 1: N = 20, 13 women; study 2: N = 20, 17 women), participants evaluated the taste of cinder toffee while listening to either of two soundscapes associated with sweet and bitter taste, respectively, or no sound. In study 1, participants rated the taste on a visual-analog scale (VAS) anchored with "bitter" and "sweet", aiming to replicate a previous study (Crisinel et al.,). In contrast, four separate scales were used in study 2 to report the extent of bitter, sweet, sour, and salty taste to test whether taste qualities were influenced by sound differentially. Additionally, taste intensity and pleasantness were rated in both studies. Taste intensity was increased in the presence of a sound, while pleasantness was not affected. In study 1, sound shifted bitter-sweet ratings in the direction of the congruent sound, i.e. samples tasted sweeter with "sweet" sound and more bitter with "bitter" sound, replicating Crisinel et al.'s () results. However, this effect was abolished when a "no-sound" control was included in the statistical model. Taste ratings in study 2 showed no effect of sound on any specific taste quality, suggesting that the influence of sound on taste in study 1 reflects an artifact of the scale rather than an actual shift in perception. Together, the data provide evidence for taste-sound correspondences without effects on taste-quality specific perception.}, } @article {pmid30025270, year = {2018}, author = {Halcrow, SE and Killgrove, K and Robbins Schug, G and Knapp, M and Huffer, D and Arriaza, B and Jungers, W and Gunter, J}, title = {On engagement with anthropology: A critical evaluation of skeletal and developmental abnormalities in the Atacama preterm baby and issues of forensic and bioarchaeological research ethics. Response to Bhattacharya et al. "Whole-genome sequencing of Atacama skeleton shows novel mutations linked with dysplasia" in Genome Research, 2018, 28: 423-431. Doi: 10.1101/gr.223693.117.}, journal = {International journal of paleopathology}, volume = {22}, number = {}, pages = {97-100}, doi = {10.1016/j.ijpp.2018.06.007}, pmid = {30025270}, issn = {1879-9825}, mesh = {*Anthropology ; Ethics, Research ; Humans ; Infant, Newborn ; Mutation ; *Research ; Whole Genome Sequencing ; }, abstract = {Here we evaluate Bhattacharya et al.'s (2018) recent paper "Whole-genome sequencing of Atacama skeleton shows novel mutations linked with dysplasia" published in Genome Research. In this short report, we examine the hypothesis that the so-called "Atacama skeleton" has skeletal abnormalities indicative of dysplasia, critique the validity of the interpretations of disease based on genomic analyses, and comment on the ethics of research on this partially mummified human foetus. The current paper acts as a case study of the importance of using an anthropological approach for aDNA research on human remains. A critical evaluation of the ethically controversial paper by Bhattacharya et al. highlights how an understanding of skeletal biological processes, including normal and abnormal growth and development, taphonomic processes, environmental context, and close attention to ethical issues of dealing with human remains, is vital to scientific interpretations. To this end, close collaboration with palaeopathologists and local archaeologists through appropriate peer-reviewed journals will add to the rigour of scientific interpretation and circumvent misinterpretation.}, } @article {pmid30018544, year = {2018}, author = {He, Q and McNamara, TP}, title = {Virtual Orientation Overrides Physical Orientation to Define a Reference Frame in Spatial Updating.}, journal = {Frontiers in human neuroscience}, volume = {12}, number = {}, pages = {269}, pmid = {30018544}, issn = {1662-5161}, abstract = {Previous studies showed that people could use either an egocentric or allocentric reference frame in spatial updating with body-based cues (i.e., physical body movements), but the adopted reference frame was anchored by the physical egocentric front when body-based cues were constrained. A recent study (He et al., 2018) showed that even without body-based cues, the orientation participants initially faced in the virtual environment (VE; initial heading) could be used to establish a reference frame, suggesting that the physical egocentric front could be overridden by a virtual orientation. In the current project, we aimed to: (a) replicate He et al.'s (2018) finding; (b) examine when the reference frame defined by the virtual initial heading was established; and (c) investigate the cognitive processes in establishing the initial heading as a reference frame. In four experiments, we were able to replicate the previous findings and found that the reference frame defined by the initial heading was established during spatial updating. More importantly, the reference frame defined by the initial heading was egocentric and participants did not need to know the orientation of their initial heading at the beginning of spatial updating to be able to use it. We discuss the cognitive processes of reference frame selection in spatial updating when body-based cues are absent.}, } @article {pmid30017836, year = {2018}, author = {Rzezak, P and Moschetta, SP and Mendonça, M and Paiva, MLMN and Coan, AC and Guerreiro, C and Valente, KDR}, title = {Higher IQ in juvenile myoclonic epilepsy: Dodging cognitive obstacles and "masking" impairments.}, journal = {Epilepsy & behavior : E&B}, volume = {86}, number = {}, pages = {124-130}, doi = {10.1016/j.yebeh.2018.05.029}, pmid = {30017836}, issn = {1525-5069}, mesh = {Adolescent ; Adult ; Attention ; Cognition ; Executive Function ; Female ; Healthy Volunteers ; Humans ; Impulsive Behavior ; *Intelligence ; Intelligence Tests ; Male ; Middle Aged ; Myoclonic Epilepsy, Juvenile/*psychology ; Neuropsychological Tests ; Stroop Test ; Trail Making Test ; Word Association Tests ; Young Adult ; }, abstract = {Executive deficits and impulsiveness are extensively reported in juvenile myoclonic epilepsy (JME). Previous literature suggests that intelligence may mediate these deficits. In this study, we evaluated and compared the performance of adults with JME with high and low intelligence quotient (IQ) and controls on tasks for executive function (EF) and impulsive traits. We investigated the neuropsychological performance of 53 adults with JME and below average IQ (57% women; 26.9 [±7.88] years; mean IQ: 89.8 [±5.1]), 26 adults with JME and average or above average IQ (53.8% women; 28.2 [±9.33] years; mean IQ: 110.7 [±8.3]), 38 controls with below average IQ (55% women; 28.4 [±8.4] years; mean IQ: 90.1 [±5.8]), and 31 controls with average or above average IQ (61.3% women; 32.20 [±11.3] years; mean IQ: 111.6 [±10.5]) with a comprehensive battery of neuropsychological tests that measure executive/attentional function. Impulsive traits were assessed using the Cloninger et al.'s Temperament and Character Inventory (novelty seeking (NS) domain). The group with JME with higher IQ presented worse performance compared with controls with higher IQ on Controlled Oral Word Association (COWA) and Wisconsin Card Sorting Test (WCST) (errors). This group showed worse performance than controls with lower IQ on Stroop Color-Word Test (SCT) 1, Trail Making (TM) A, COWA, and WCST (errors). Patients with lower IQ showed worse performance than controls with higher IQ on Digit Span Forward (DSF), Digit Span Backward (DSB), SCT1, SCT2, SCT3, TM A, COWA, and WCST (errors and failure to maintain set). Patients with lower IQ showed worse performance than controls with lower IQ on DSF, DSB, SCT1, SCT2, SCT3, TM A, TM B, COWA, and WCST (errors and failure to maintain set). Patients from groups with low and high IQ showed higher scores than controls with higher and lower IQ on impulsivity for NS1 and NS2 (except for patients with higher IQ versus controls with lower IQ). Adults with JME and higher IQ show less evidence of EF deficits compared with those with JME and below average IQ, suggesting that a higher degree of intellectual efficiency may act as a compensatory mechanism. However, it does not minimize some aspects of impulsive traits. Patients with JME and higher cognitive reserve may create strategies to dodge their cognitive obstacles. In this context, intelligence may protect and, at the same time, "mask" impairments that could be detected earlier.}, } @article {pmid30015606, year = {2018}, author = {Wicherts, JM}, title = {IGNORING PSYCHOMETRIC PROBLEMS IN THE STUDY OF GROUP DIFFERENCES IN COGNITIVE TEST PERFORMANCE.}, journal = {Journal of biosocial science}, volume = {50}, number = {6}, pages = {868-869}, doi = {10.1017/S0021932018000172}, pmid = {30015606}, issn = {1469-7599}, mesh = {Adolescent ; Child ; *Cognition ; Humans ; Intelligence Tests ; Psychometrics ; Saudi Arabia ; }, abstract = {In a recent study, te Nijenhuis et al. (2017) used a version of Jensen's method of correlated vectors to study the nature of ethnic group differences on Raven's Progressive Matrices test. In this comment, the author points out that this method has been shown to be psychometrically inappropriate in studying group differences in performance on dichotomous (correctly or incorrectly scored) items. Specifically, the method uses item statistics like the item-total correlation that necessarily differ across groups differing in ability and employs a linear model to test inherent non-linear relations. Wicherts (2017) showed that this method can provide correlations far exceeding r=0.44 in cases where the group differences cannot possibly be on g because the items measure different traits across the groups. The psychometric problems with their method cast serious doubts on te Nijenhuis et al.'s conclusions concerning the role of g in the studied group difference in cognitive test performance.}, } @article {pmid30010408, year = {2018}, author = {Van Rooij, AJ and Nijkamp, LM}, title = {Addressing problematic video game use: A multimethod, dual-context perspective on leisure-time use.}, journal = {Journal of behavioral addictions}, volume = {7}, number = {3}, pages = {526-530}, pmid = {30010408}, issn = {2063-5303}, mesh = {*Behavior, Addictive ; Games, Recreational ; Humans ; Leisure Activities ; *Video Games ; }, abstract = {A more integrative approach to the prevention of problematic gaming behavior is recommended in Király et al.'s review. We discuss the Dutch policy responses to problematic gaming behavior and suggest two alternatives to the dominant survey research approach to achieve this. Employing time-use/diary studies allows us to map out the full scope of leisure-time use and employing log-data analysis improves our understanding of gamer behavior within the virtual context. All of these approaches would benefit from accounting for the diversity of within-virtual context behavior. The approach is summarized as a multimethod, dual-context approach to understanding leisure-time behavior.}, } @article {pmid30003478, year = {2018}, author = {Girod, C and Herbst, JH}, title = {Capsule Commentary on Christian et al.'s "Measuring the Health of an Invisible Population: Lessons from the Colorado Transgender Health Survey".}, journal = {Journal of general internal medicine}, volume = {33}, number = {10}, pages = {1780}, pmid = {30003478}, issn = {1525-1497}, mesh = {Colorado ; Health Surveys ; Humans ; Surveys and Questionnaires ; *Transgender Persons ; *Transsexualism ; Male ; Female ; }, } @article {pmid29992426, year = {2018}, author = {Alsabbagh, MW}, title = {Capsule Commentary on Goto et al.'s Incidence of Acute Cardiovascular Event After Acute Exacerbation of COPD.}, journal = {Journal of general internal medicine}, volume = {33}, number = {9}, pages = {1552}, pmid = {29992426}, issn = {1525-1497}, mesh = {*Cardiovascular Diseases ; Humans ; Incidence ; *Pulmonary Disease, Chronic Obstructive ; }, } @article {pmid29985025, year = {2018}, author = {Yu, JJ and Downes, PE and Carter, KM and O'Boyle, E}, title = {The heterogeneity problem in meta-analytic structural equation modeling (MASEM) revisited: A reply to Cheung.}, journal = {The Journal of applied psychology}, volume = {103}, number = {7}, pages = {804-811}, doi = {10.1037/apl0000328}, pmid = {29985025}, issn = {1939-1854}, mesh = {Humans ; *Latent Class Analysis ; Models, Statistical ; }, abstract = {Yu, Downes, Carter, and O'Boyle (2016) introduce a new technique to incorporate effect size heterogeneity into meta-analytic structural equation modeling (MASEM) labeled full information meta-analytical structural equation modeling (FIMASEM). Cheung's (2018) commentary raises concerns about the viability of FIMASEM and provides its initial validation. In this reply, we briefly respond to those concerns noting how they relate to Yu et al.'s original conclusions, general MASEM practices, and operational decisions within the FIMASEM procedure. We synthesize Cheung's criticisms and build on his findings to lay out a research agenda for the future of MASEM and the role that our technique might play in it. In doing so, we clarify the conceptual nature of FIMASEM, identity inferential mistakes that current MASEM studies are likely to make, and offer specific and actionable recommendations in terms of the types of research questions FIMASEM is best suited to address and how FIMASEM results can best be interpreted and reported. (PsycINFO Database Record}, } @article {pmid29983665, year = {2018}, author = {Rauck, RC and Blevins, JL and Cross, MB}, title = {Component Placement Accuracy in Unicompartmental Knee Arthroplasty Is Improved with Robotic-Assisted Surgery: Will It Have an Effect on Outcomes?.}, journal = {HSS journal : the musculoskeletal journal of Hospital for Special Surgery}, volume = {14}, number = {2}, pages = {211-213}, pmid = {29983665}, issn = {1556-3316}, abstract = {Bell et al.'s "Improved Accuracy of Component Positioning with Robotic-Assisted Unicompartmental Knee Arthroplasty: Data from a Prospective, Randomized Controlled Study" compared the accuracy of a robotic-assisted unicompartmental knee arthroplasty (UKA) using the MAKO Robotic Interactive Orthopedic Arm (RIO) system to a conventional UKA using standardized instrumentation. This review examines the authors' findings and their relevance to clinical practice. Bell et al. conclude that the MAKO RIO system leads to more accurate implantation of both the tibial and femoral components in UKA in the sagittal, coronal, and axial planes. This well-designed, level I study suggests what many arthroplasty surgeons assume about robotic assistance, which admittedly is of unknown clinical significance at this time. Evaluating this article in the context of the current literature provides valuable insight into areas in need of future investigation. The effect of implant positioning on long-term clinical outcomes and implant survivorship remains unclear. Long-term follow-up studies are needed to determine the role of robotic-assisted arthroplasty in the future.}, } @article {pmid29977214, year = {2018}, author = {Telga, M and de Lemus, S and Cañadas, E and Rodríguez-Bailón, R and Lupiáñez, J}, title = {Category-Based Learning About Deviant Outgroup Members Hinders Performance in Trust Decision Making.}, journal = {Frontiers in psychology}, volume = {9}, number = {}, pages = {1008}, pmid = {29977214}, issn = {1664-1078}, abstract = {The present research examines whether individuation and categorization processes influence trust decisions about strangers at first and across repeated interactions. In a partial replication of the study reported by Cañadas et al. (2015), participants played an adaptation of the multi-round trust game paradigm and had to decide whether or not to cooperate with unknown partners. Gender (Study 1a) and ethnicity (Studies 1b, 2, and 3) served to create distinct social categories among the game partners, whose reciprocation rates were manipulated at group and individual levels. At the group level, two social groups (i.e., ingroup vs. outgroup) were associated with opposite reciprocation rates (i.e., high vs. low reciprocation rate). At the individual level, consistency was manipulated by altering the reciprocation rate of one out of four members of each social group. That is, there was one inconsistent individual in each group showing a pattern of reciprocation opposite to the group reciprocation rate. Our data, contrary to Cañadas et al.'s (2015) findings, suggested that ingroup partners were individuated given that participants made their decisions to cooperate with the trustees according to their individual reciprocation rate and independently of the group reciprocation rate. In contrast, decisions about outgroup partners (i.e., men in Study 1a and Blacks in Studies 1b, 2, and 3) were affected by category-based thinking. At the same time, in comparison with ingroup, greater cooperation was observed with ethnic outgroups but not with gender outgroups. The consistency of our results with the previous literature on social categorization and across the three experiments seems to indicate they are reliable, supporting the hypothesis that categorization and individuation processes guide trust decision-making, promoting individuation mainly for ingroup and categorization among outgroup members.}, } @article {pmid29970280, year = {2018}, author = {Leibovitz, Z and Lerman-Sagie, T}, title = {Diagnostic approach to fetal microcephaly.}, journal = {European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society}, volume = {22}, number = {6}, pages = {935-943}, doi = {10.1016/j.ejpn.2018.06.002}, pmid = {29970280}, issn = {1532-2130}, mesh = {Biometry/*methods ; Female ; Fetus/*diagnostic imaging ; Gestational Age ; Head/*diagnostic imaging/embryology ; Humans ; Infant, Newborn ; Male ; Microcephaly/*diagnostic imaging ; Pregnancy ; Prenatal Diagnosis/*methods ; Reference Values ; Ultrasonography, Prenatal ; }, abstract = {Microcephaly in utero is conventionally defined as a fetal head circumference (HC) 3SD below the mean for gestational age according to Jeanty et al.'s reference range. Prediction of microcephaly at birth (micB) based on conventional prenatal biometry is associated with a high percentage of false positive diagnoses and as a result, in countries in which it is an option, termination of pregnancy may be offered in cases that would have culminated in birth of a normocephalic child. A false negative diagnosis is rarer, but may lead to the birth of a symptomatic microcephalic child. In this review we present the results of our recent studies aimed at improvement of accurate prenatal detection of microcephaly including: (1), application of two new reference ranges for fetal HC in cases with a prenatal diagnosis of microcephaly based on the conventional reference; (2) assessment whether integration of additional parameters (stricter fetal HC cut-offs, small-for-gestational age (SGA), decreased HC/abdominal circumference and HC/femur length ratios, presence of associated malformations and family history) can improve prediction; (3), estimation of the difference between Z-scores of prenatal HC and the corresponding occipitofrontal circumference (OFC) at birth in order to propose an adjustment for better prediction of the actual OFC deviation at birth; (4), assessment whether micB diagnosis can be improved by accurate detection of false positive Fmic cases whose small HC is due to an acrocephalic-like head deformation by applying a new reference range of a vertical measurement of the fetal head: foramen magnum-to-cranium distance (FCD). The conventional and new reference ranges for fetal HC, all result in considerable over-diagnosis of fetal microcephaly (ranging from 43% to 33%). The use of the new references does not significantly improve micB prediction compared with the conventional one, whilst integrating additional parameters results in a better positive predictive value (PPV), but an increase in false negatives. The degree of Fmic severity is significantly over-estimated compared to the corresponding micB. The difference between the postnatal OFC deviation from the mean and the prenatal HC ranges from -0.74 SD to -1.95 SD for various fetal HC references. Application of the reference range for vertical cranial dimensions enables exclusion of fetuses with a small HC associated with a vertical cranial deformity without missing those with actual micB. Combining the fetal HC with the developed FCD criteria raised the PPV of micB to 78%. CONCLUSIONS: Prediction of micB can be improved by integrating additional parameters and by application of the FCD criteria, however the correct diagnosis of Fmic remains challenging. An algorithm for evaluation of fetal microcephaly is provided.}, } @article {pmid29960690, year = {2018}, author = {Daniolos, PT}, title = {Identity, Conformity, and Nonconformity: A Closer Look.}, journal = {Journal of the American Academy of Child and Adolescent Psychiatry}, volume = {57}, number = {7}, pages = {460-461}, doi = {10.1016/j.jaac.2018.05.001}, pmid = {29960690}, issn = {1527-5418}, mesh = {Adolescent ; Canada ; Child ; Female ; *Gender Dysphoria ; *Gender Identity ; Humans ; Male ; Mental Health ; Social Behavior ; }, abstract = {As clinicians, we have been vigilant to screen for underlying psychopathology in children and adolescents who meet criteria for gender dysphoria (GD) based on the risk these individuals have for developing externalizing and/or internalizing disorders, likely driven by a stigmatizing society. However, we have not paid careful attention to an often overlooked population, namely gender-nonconforming (GNC) children-especially those in community samples-who do not meet criteria for GD per se but who, according to the well-done and thought-provoking study featured in this issue, van der Miesen et al.'s "Behavioral and Emotional Problems in Gender-Nonconforming Children: A Canadian Community-Based Study,"[1] appear to share some similar psychiatric vulnerabilities as their peers with GD, with some unique features noted for natal boys versus natal girls. The few studies that have looked at this group of children have relied on clinical samples, which complicates whether the increased rates of psychopathology are in fact due to GNC-related factors versus inherently higher rates of psychopathology in clinical samples. Because of this, previous studies using clinical samples might overestimate the rates of psychopathology in GNC youths. Van der Miesen et al. smartly attempted to avoid that bias by drawing participants from the community and by excluding participants with any previous mental health diagnoses, including GD.[1] This study is a refreshing shift, delving into community samples and using a validated measure, the Gender Identity Questionnaire for Children (GIQC), thus allowing comparisons to be made with prior clinical samples.}, } @article {pmid29957304, year = {2018}, author = {Harriger, JA and Serier, KN and Luedke, M and Robertson, S and Bojorquez, A}, title = {Appearance-related themes in children's animated movies released between 2004 and 2016: A content analysis.}, journal = {Body image}, volume = {26}, number = {}, pages = {78-82}, doi = {10.1016/j.bodyim.2018.06.004}, pmid = {29957304}, issn = {1873-6807}, mesh = {*Body Composition ; Body Image/*psychology ; *Body Weight ; Child ; Female ; *Human Body ; Humans ; Male ; *Motion Pictures ; }, abstract = {Research suggests that children demonstrate an awareness of cultural messages regarding appearance; specifically, that thinness is desirable and fatness is objectionable. In 2004, Herbozo and colleagues published research examining the content of popular children's movies. This widely cited study has provided the foundation for various studies examining the impact of media on children. The purpose of the current study was to extend the findings of Herbozo et al.'s (2004) research to include more recent movies. Two independent coders viewed the 25 top-grossing U.S. animated feature films since 2004 and indicated the number of appearance-related themes present in each movie. Movies in the current study contained significantly more appearance-related themes focused on male muscularity and the role of personal control related to weight compared to earlier films. These findings are consistent with cultural trends and demonstrate the importance of continued examination of children's media influences.}, } @article {pmid29956007, year = {2018}, author = {Kumar, V and Jangirala, S and Ahmad, M}, title = {An Efficient Mutual Authentication Framework for Healthcare System in Cloud Computing.}, journal = {Journal of medical systems}, volume = {42}, number = {8}, pages = {142}, pmid = {29956007}, issn = {1573-689X}, mesh = {*Cloud Computing ; *Computer Security ; Confidentiality ; Humans ; Information Systems ; *Telemedicine ; }, abstract = {The increasing role of Telecare Medicine Information Systems (TMIS) makes its accessibility for patients to explore medical treatment, accumulate and approach medical data through internet connectivity. Security and privacy preservation is necessary for medical data of the patient in TMIS because of the very perceptive purpose. Recently, Mohit et al.'s proposed a mutual authentication protocol for TMIS in the cloud computing environment. In this work, we reviewed their protocol and found that it is not secure against stolen verifier attack, many logged in patient attack, patient anonymity, impersonation attack, and fails to protect session key. For enhancement of security level, we proposed a new mutual authentication protocol for the similar environment. The presented framework is also more capable in terms of computation cost. In addition, the security evaluation of the protocol protects resilience of all possible security attributes, and we also explored formal security evaluation based on random oracle model. The performance of the proposed protocol is much better in comparison to the existing protocol.}, } @article {pmid29945519, year = {2018}, author = {Rajyaguru, DJ and Borgert, AJ and Halfdanarson, TR and Truty, MJ and Kurup, AN and Go, RS}, title = {Reply to E.L. Pollom et al, N. Ohri et al, A. Fiorentino et al, D.R. Wahl et al, N. Kim et al, J. Boda-Heggemann et al, S. Rana et al, N. Sanuki et al, J.R. Olsen et al, G.L. Smith et al, and A. Shinde et al.}, journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology}, volume = {36}, number = {24}, pages = {2567-2569}, doi = {10.1200/JCO.2018.78.6418}, pmid = {29945519}, issn = {1527-7755}, mesh = {*Carcinoma, Hepatocellular ; *Catheter Ablation ; Humans ; *Liver Neoplasms ; Radiofrequency Ablation ; *Radiosurgery ; }, } @article {pmid29943172, year = {2018}, author = {Trippas, D and Kellen, D and Singmann, H and Pennycook, G and Koehler, DJ and Fugelsang, JA and Dubé, C}, title = {Characterizing belief bias in syllogistic reasoning: A hierarchical Bayesian meta-analysis of ROC data.}, journal = {Psychonomic bulletin & review}, volume = {25}, number = {6}, pages = {2141-2174}, pmid = {29943172}, issn = {1531-5320}, mesh = {*Bayes Theorem ; Humans ; *Logic ; *ROC Curve ; *Thinking ; }, abstract = {The belief-bias effect is one of the most-studied biases in reasoning. A recent study of the phenomenon using the signal detection theory (SDT) model called into question all theoretical accounts of belief bias by demonstrating that belief-based differences in the ability to discriminate between valid and invalid syllogisms may be an artifact stemming from the use of inappropriate linear measurement models such as analysis of variance (Dube et al., Psychological Review, 117(3), 831-863, 2010). The discrepancy between Dube et al.'s, Psychological Review, 117(3), 831-863 (2010) results and the previous three decades of work, together with former's methodological criticisms suggests the need to revisit earlier results, this time collecting confidence-rating responses. Using a hierarchical Bayesian meta-analysis, we reanalyzed a corpus of 22 confidence-rating studies (N = 993). The results indicated that extensive replications using confidence-rating data are unnecessary as the observed receiver operating characteristic functions are not systematically asymmetric. These results were subsequently corroborated by a novel experimental design based on SDT's generalized area theorem. Although the meta-analysis confirms that believability does not influence discriminability unconditionally, it also confirmed previous results that factors such as individual differences mediate the effect. The main point is that data from previous and future studies can be safely analyzed using appropriate hierarchical methods that do not require confidence ratings. More generally, our results set a new standard for analyzing data and evaluating theories in reasoning. Important methodological and theoretical considerations for future work on belief bias and related domains are discussed.}, } @article {pmid29937948, year = {2018}, author = {Nyholm, S}, title = {Is the Personal Identity Debate a "Threat" to Neurosurgical Patients? A Reply to Müller et al.}, journal = {Neuroethics}, volume = {11}, number = {2}, pages = {229-235}, pmid = {29937948}, issn = {1874-5490}, abstract = {In their article in this journal, Sabine Müller, Merlin Bittlinger, and Henrik Walter launch a sweeping attack against what they call the "personal identity debate" as it relates to patients treated with deep brain stimulation (DBS). In this critique offered by Müller et al., the personal identity debate is said to: (a) be metaphysical in a problematic way, (b) constitute a threat to patients, and (c) use "vague" and "contradictory" statements from patients and their families as direct evidence for metaphysical theories. In this response, I critically evaluate Müller et al.'s argument, with a special focus on these three just-mentioned aspects of their discussion. My conclusion is that Müller et al.'s overall argument is problematic. It overgeneralizes criticisms that may apply to some, but certainly not to all, contributions to what they call the personal identity-debate. Moreover, it rests on a problematic conception of what much of this debate is about. Nor is Müller et al.'s overall argument fair in its assessment of the methodology used by most participants in the debate. For these reasons, we should be skeptical of Müller et al.'s claim that the "personal identity debate" is a "threat to neurosurgical patients".}, } @article {pmid29937255, year = {2018}, author = {Boyd, MR and Powell, BJ and Endicott, D and Lewis, CC}, title = {A Method for Tracking Implementation Strategies: An Exemplar Implementing Measurement-Based Care in Community Behavioral Health Clinics.}, journal = {Behavior therapy}, volume = {49}, number = {4}, pages = {525-537}, pmid = {29937255}, issn = {1878-1888}, support = {K01 MH113806/MH/NIMH NIH HHS/United States ; L30 MH108060/MH/NIMH NIH HHS/United States ; R01 MH103310/MH/NIMH NIH HHS/United States ; }, mesh = {Adult ; Cluster Analysis ; *Community Mental Health Centers/standards ; Female ; Health Plan Implementation/*methods/standards ; Humans ; Male ; Middle Aged ; Patient Care/*methods/standards ; Psychiatry/*methods/standards ; }, abstract = {Implementation experts suggest tailoring strategies to the intended context may enhance outcomes. However, it remains unclear which strategies are best suited to address specific barriers to implementation, in part because few measurement methods exist that adhere to recommendations for reporting. In the context of a dynamic cluster randomized trial comparing a standardized to tailored approach to implementing measurement-based care (MBC), this study aimed to (a) describe a method for tracking implementation strategies, (b) demonstrate the method by tracking strategies generated by teams tasked with implementing MBC at their clinics in the tailored condition, and (c) conduct preliminary examinations of the relation between strategy use and implementation outcomes (i.e., self-reported fidelity to MBC). The method consisted of a coding form based on Proctor, Powell, and McMillen (2013) implementation strategy reporting guidelines and Powell et al.'s (2012) taxonomy to facilitate specification of the strategies. A trained research specialist coded digitally recorded implementation team meetings. The method allowed for the following characterization of strategy use. Each site generated 39 unique strategies across an average of six meetings in five months. There was little variability in the use of types of implementation strategies across sites with the following order of prevalence: quality management (50.00%), restructuring (16.53%), communication (15.68%), education (8.90%), planning (7.20%), and financing (1.69%). We identified a new category of strategies not captured by the existing taxonomy, labeled "communication." There was no evidence that number of implementation strategies enacted was statistically significantly associated with changes in self-reported fidelity to MBC-however, financing strategies were associated with increased fidelity. This method has the capacity to yield rich data that will inform investigations into tailored implementation approaches.}, } @article {pmid29936021, year = {2018}, author = {Lacroix, E and Tavares, H and von Ranson, KM}, title = {Moving beyond the "eating addiction" versus "food addiction" debate: Comment on Schulte et al. (2017).}, journal = {Appetite}, volume = {130}, number = {}, pages = {286-292}, doi = {10.1016/j.appet.2018.06.025}, pmid = {29936021}, issn = {1095-8304}, mesh = {*Behavior, Addictive ; Eating ; *Feeding and Eating Disorders ; Food ; *Food Addiction ; Humans ; }, abstract = {In a recent commentary, Schulte et al. (2017) argued that addictive-like eating should be conceptualized as a substance use disorder rather than a behavioural addiction, and noted that many parallels that Hebebrand et al. (2014) drew between addictive-like eating and behavioural addictions apply likewise to substance use disorders. However, we argue that many of the arguments advanced by Schulte et al. (2017) in support of a substance-based food addiction model, including the important role played by ingested substances, are nonspecific. That is, these arguments apply equally well to behavioural addictions and other mental disorders, notably eating disorders, which raises the question of whether the phenomenon of addictive-like eating is encompassed by existing eating disorder diagnoses. Similarities between addictive-like eating and substance use, no matter how compelling, do not ensure the validity or clinical utility of a substance-based food addiction model and should not drive the conceptualization of addictive-like eating. The present commentary discusses problems with Schulte et al.'s (2017) arguments for substance-based food addiction, and draws attention to alternative conceptualizations of addictive-like eating which risk being overlooked when this conversation is framed as a dichotomous debate between the food and eating addiction models.}, } @article {pmid29912021, year = {2018}, author = {Cox, AJ and Ferguson, PJ}, title = {Update on the genetics of nonbacterial osteomyelitis in humans.}, journal = {Current opinion in rheumatology}, volume = {30}, number = {5}, pages = {521-525}, doi = {10.1097/BOR.0000000000000530}, pmid = {29912021}, issn = {1531-6963}, support = {R01 AR059703/AR/NIAMS NIH HHS/United States ; R01 NS098590/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Cell Adhesion Molecules/genetics ; Chromosomes, Human, Pair 18/genetics ; Chronic Disease ; Cytoskeletal Proteins/genetics ; Genetic Predisposition to Disease ; Humans ; Inflammasomes/genetics ; Mice ; Mutation ; Osteomyelitis/*genetics ; }, abstract = {PURPOSE OF REVIEW: To summarize the current advances in our understanding or the genetic basis of nonbacterial osteomyelitis.

RECENT FINDINGS: Chronic recurrent multifocal osteomyelitis (CRMO) is a complex genetic disorder. Past discoveries identified several single gene defects (LPIN2, Pstpip2 and IL1RN) that cause IL-1-mediated sterile multifocal osteomyelitis. Recently Lorden et al.'s studies show that LIPIN2 deficiency can activate the NLRP3 inflammasome through alterations in the function of P2X7 receptor providing evidence that Majeed syndrome is an NLRP3 inflammasomopathy. New gene discoveries include the identification of FBLIM1 as a CRMO susceptibility gene. Mutations in FBLIM1 were found in a consanguineous family with CRMO. Fblim1 is one of the most significantly differentially expressed gene in bone from chronic multifocal osteomyelitis (cmo) mice, plays a role in IL-10-driven anti-inflammatory responses, and is involved in the physiology of bone remodeling. Lastly, new data on the putative CRMO susceptibility locus on chromosome 18 is presented here. Using Sanger sequencing, rather than microsatellite analysis, the DS18S60 susceptibility region could not be replicated in a larger cohort.

SUMMARY: CRMO occurs in humans, nonhuman primates, dogs and mice. There is a genetic component to disease but the genetic basis has only been identified for a small percentage of all cases.}, } @article {pmid29902930, year = {2019}, author = {Somma, A and Krueger, RF and Markon, KE and Borroni, S and Fossati, A}, title = {Item Response Theory Analyses, Factor Structure, and External Correlates of the Italian Translation of the Personality Inventory for DSM-5 Short Form in Community-Dwelling Adults and Clinical Adults.}, journal = {Assessment}, volume = {26}, number = {5}, pages = {839-852}, doi = {10.1177/1073191118781006}, pmid = {29902930}, issn = {1552-3489}, mesh = {Adult ; Diagnostic and Statistical Manual of Mental Disorders ; Factor Analysis, Statistical ; Female ; Humans ; Independent Living ; Male ; Personality Disorders/*diagnosis/psychology ; *Personality Inventory ; Psychometrics ; Reproducibility of Results ; Translations ; }, abstract = {To assess the psychometric properties of the Italian translation of the 100-item short form of the Personality Inventory for DSM-5 (PID-5-SF), 2,143 community-dwelling adults (59.6% female), and 706 adult clinical participants (52.4% female) were administered the Italian translation of the PID-5. Clinical participants were also administered the Structured Clinical Interview for DSM-IV (SCID-II), and the Personality Diagnostic Questionnaire-4+ (PDQ-4+). Item response theory analysis showed that all proposed PID-5-SF items showed adequate item discrimination parameters in both community-dwelling adults and clinical adults. All PID-5-SF trait scales showed satisfactory internal consistency estimates. PID-5-SF five-factor structure closely matched the factor structure of the PID-5 in both community-dwelling participants and clinical participants and was invariant across the two samples that participated in this study. Moreover, the factor structure of the PID-5-SF closely replicated the factor of the PID-5-SF that was originally reported in Maples et al.'s study. In our clinical sample, dominance analysis results showed that PID-5-SF scales explained a nonnegligible and significant amount of variance in both SCID-II and PDQ-4+ ratings of selected DSM-5 Section II personality disorder, and the use of the PID-5-SF did not result in a substantial loss of information as compared with the original PID-5.}, } @article {pmid29896492, year = {2018}, author = {Bach, M and Hoffmann, MB}, title = {Calculation and plotting of retinal nerve fiber paths based on Jansonius et al. 2009/2012 with an R program.}, journal = {Data in brief}, volume = {18}, number = {}, pages = {66-68}, pmid = {29896492}, issn = {2352-3409}, abstract = {The data presented in this article are related to the research article entitled "Retinal conduction speed analysis reveals different origins of the P50 and N95 components of the (multifocal) pattern electroretinogram" (Bach et al., 2018) [1]. That analysis required the individual length data of the retinal nerve fibers (from ganglion cell body to optic nerve head, depending on the position of the ganglion cell body). Jansonius et al. (2009, 2012) [2,3] mathematically modeled the path morphology of the human retinal nerve fibers. We here present a working implementation with source code (for the free and open-source programming environment "R") of the Jansonius' formulas, including all errata. One file defines Jansonius et al.'s "phi" function. This function allows quantitative modelling of paths (and any measures derived from them) of the retinal nerve fibers. As a working demonstration, a second file contains a graph which plots samples of nerve fibers. The included R code runs in base R without the need of any additional packages.}, } @article {pmid29894580, year = {2018}, author = {Linnen, CR}, title = {Predicting evolutionary predictability.}, journal = {Molecular ecology}, volume = {27}, number = {12}, pages = {2647-2650}, doi = {10.1111/mec.14716}, pmid = {29894580}, issn = {1365-294X}, mesh = {Animals ; *Butterflies ; Gene Frequency ; Genomics ; *Melissa ; Plants ; }, abstract = {The observation that phenotypic convergence and genetic convergence are widespread in nature implies that evolution is at least somewhat predictable. But to what extent and under what circumstances? In other words, how predictable is evolutionary predictability? Answering this question requires going beyond documenting examples of repeated evolution to actually quantifying predictability at different hierarchical levels. At present, few such studies exist. In this issue of Molecular Ecology, Chaturvedi et al. () quantify the predictability of genomewide changes that accompany shifts to an introduced host plant (alfalfa) in populations of the Melissa blue butterfly (Lycaeides melissa). They evaluate predictability in two contexts: (i) overlap in host-associated loci among populations that have independently colonized alfalfa, and (ii) overlap between host-associated loci in nature and loci associated with host performance in laboratory experiments. Overall, they find that the genomic changes that accompany host shifts in this system are indeed somewhat predictable. However, the degree of predictability depends on the type of comparison (among natural populations vs. between natural and experimental populations), type of convergence (specific genomic locations vs. direction of allele frequency change), geographic scale (rangewide vs. specific population pairs) and location in the genome (autosomes vs. sex chromosomes). Together with a handful of comparable data sets, Chaturvedi et al.'s () work suggests that the relative contribution of stochastic and deterministic processes to genomewide responses to novel selection pressures may be highly variable, but possibly predictably so.}, } @article {pmid29892367, year = {2018}, author = {van Casteren, A and Lucas, PW and Strait, DS and Michael, S and Bierwisch, N and Schwarzer, N and Al-Fadhalah, KJ and Almusallam, AS and Thai, LA and Saji, S and Shekeban, A and Swain, MV}, title = {Evidence that metallic proxies are unsuitable for assessing the mechanics of microwear formation and a new theory of the meaning of microwear.}, journal = {Royal Society open science}, volume = {5}, number = {5}, pages = {171699}, pmid = {29892367}, issn = {2054-5703}, abstract = {Mammalian tooth wear research reveals contrasting patterns seemingly linked to diet: irregularly pitted enamel surfaces, possibly from consuming hard seeds, versus roughly aligned linearly grooved surfaces, associated with eating tough leaves. These patterns are important for assigning diet to fossils, including hominins. However, experiments establishing conditions necessary for such damage challenge this paradigm. Lucas et al. (Lucas et al. 2013 J. R. Soc. Interface10, 20120923. (doi:10.1098/rsif.2012.0923)) slid natural objects against enamel, concluding anything less hard than enamel would rub, not abrade, its surface (producing no immediate wear). This category includes all organic plant matter. Particles harder than enamel, with sufficiently angular surfaces, could abrade it immediately, prerequisites that silica/silicate particles alone possess. Xia et al. (Xia, Zheng, Huang, Tian, Chen, Zhou, Ungar, Qian. 2015 Proc. Natl Acad. Sci. USA112, 10 669-10 672. (doi:10.1073/pnas.1509491112)) countered with experiments using brass and aluminium balls. Their bulk hardness was lower than enamel, but the latter was abraded. We examined the ball exteriors to address this discrepancy. The aluminium was surfaced by a thin rough oxide layer harder than enamel. Brass surfaces were smoother, but work hardening during manufacture gave them comparable or higher hardness than enamel. We conclude that Xia et al.'s results are actually predicted by the mechanical model of Lucas et al. To explain wear patterns, we present a new model of textural formation, based on particle properties and presence/absence of silica(tes).}, } @article {pmid29890885, year = {2018}, author = {Haseeb, M and Muzafar, K and Ghani, A and Bhat, KA and Butt, MF}, title = {A fresh look at radial shaft fracture fixation: The lateral approach to the radius.}, journal = {Journal of orthopaedic surgery (Hong Kong)}, volume = {26}, number = {2}, pages = {2309499018780871}, doi = {10.1177/2309499018780871}, pmid = {29890885}, issn = {2309-4990}, mesh = {Adolescent ; Adult ; *Bone Plates ; Female ; Fracture Fixation, Internal/*methods ; Humans ; Male ; Middle Aged ; Operative Time ; Radiography/methods ; Radius/*diagnostic imaging/injuries/surgery ; Radius Fractures/diagnosis/*surgery ; Young Adult ; }, abstract = {INTRODUCTION: Open reduction and internal fixation using plates is the gold standard for the treatment of displaced forearm bone fractures in adults. The ulna being subcutaneous throughout has a constant approach. However, the radius is approached from either the dorsal or the volar side. Both the dorsal and the volar approaches to the radial shaft involve meticulous dissection and preservation of important neurovascular structures. The posterior interosseus nerve is at risk in the dorsal approach and the radial artery and its branches in the volar approach. Dissection of these structures also adds to the operative time. The possibility of a third alternate approach was perceived, which could decrease the potential risks of the conventional approaches.

PATIENTS AND METHODS: Sixteen patients with radial shaft fractures in the middle third were operated on using the lateral approach: 6 of them had isolated radius fracture and 10 had both-bone fractures. There were 13 males and three females with a mean age of 37.9 years. Limited contact dynamic compression plate or locking compression plate of 3.5 mm was used to fix all fractures. All patients were operated on within 36 h of injury and then followed up till union. Union was assessed using serial radiographs and functional outcome using Anderson et al.'s criteria. The final functional outcome was assessed at an average 6 months after surgery and the results compiled.

RESULTS: The mean operative time in isolated radius fractures was 37.5 min and that for plating of both bones was 80.7 min. Primary bone grafting of the radius was done in one case and secondary bone grafting in another patient with delayed union of the radius. Union was achieved in all cases at a mean time of 17.25 weeks. The functional outcome was excellent in 10 patients, satisfactory in 5 patients, and unsatisfactory in 1 patient.

CONCLUSION: The lateral approach is a simple approach with low operative complexity and complications. We found this approach to provide a reliably good exposure of the middle third of the radius, enabling lateral plating without complications.}, } @article {pmid29870648, year = {2017}, author = {Ádám, S and Konkoly Thege, B}, title = {Validation of the Hungarian version of Carlson's Work-Family Conflict Scale.}, journal = {Ideggyogyaszati szemle}, volume = {70}, number = {11-12}, pages = {395-406}, doi = {10.18071/isz.70.0395}, pmid = {29870648}, issn = {0019-1442}, mesh = {*Conflict, Psychological ; Cross-Cultural Comparison ; Employment/*psychology ; Factor Analysis, Statistical ; *Family Conflict ; Female ; Humans ; Male ; *Psychological Tests ; Reproducibility of Results ; Sex Factors ; Social Support ; Stress, Psychological/diagnosis/etiology ; Translating ; }, abstract = {BACKGROUND AND PURPOSE: Work-family conflict has been associated with adverse individual (e.g., cardiovascular diseases, anxiety disorders), organizational (e.g., absenteeism, lower productivity), and societal outcomes (e.g., increased use of healthcare services). However, lack of standardized measurement has hindered the comparison of data across various cultures. The purpose of this study was to develop the Hungarian version of Carlson et al.'s multidimensional Work-Family Conflict Scale and establish its reliability and validity.

METHODS: In a sample of 557 employees (145 men and 412 women), we conducted confirmatory factor analysis to investigate the factor structure and factorial invariance of the instrument across sex and data collection points and evaluated the tool's validity by assessing relationships between its dimensions and scales measuring general, marital, and job-related stress, depressive symptomatology, vital exhaustion, functional somatic symptoms, and social support.

RESULTS: Our results showed that a six-factor model, similarly to that of the original instrument, fit the data best. Internal consistency of the six dimensions and the whole instrument was adequate. Convergent and divergent validity of the instrument and discriminant validity of the dimensions were also supported by our data.

CONCLUSION: This study provides empirical support for the validity and reliability of the Hungarian version of the multidimensional Work-Family Conflict Scale. Deployment of this measure may allow for the generation of data that can be compared to those obtained in different cultural settings with the same instrument and hence advance our understanding of cross-cultural aspects of work-family conflict.}, } @article {pmid29869141, year = {2018}, author = {Vander Weg, MW}, title = {Capsule Commentary on Radomski et al.'s Physicians' Perspectives Regarding Prescription Drug Monitoring Program Use Within the Department of Veterans Affairs: a Multi-state Qualitative Study.}, journal = {Journal of general internal medicine}, volume = {33}, number = {8}, pages = {1381}, pmid = {29869141}, issn = {1525-1497}, mesh = {Humans ; *Physicians ; *Prescription Drug Monitoring Programs ; Qualitative Research ; United States ; United States Department of Veterans Affairs ; *Veterans ; }, } @article {pmid29869012, year = {2018}, author = {Alzohiry, MA and Abdelnasser, MK and Moustafa, M and Mahran, M and Bakr, H and Khalifa, Y and Abelaal, A and Atta, H and Said, GZ}, title = {Accuracy of plain antero-posterior radiographic-based methods for measurement of acetabular cup version.}, journal = {International orthopaedics}, volume = {42}, number = {12}, pages = {2777-2785}, pmid = {29869012}, issn = {1432-5195}, mesh = {Acetabulum/*diagnostic imaging/surgery ; Adult ; Aged ; Aged, 80 and over ; Arthroplasty, Replacement, Hip/adverse effects/*methods ; Bone Malalignment/*diagnostic imaging/etiology ; Female ; *Hip Prosthesis/adverse effects ; Humans ; Male ; Middle Aged ; Postoperative Period ; Radiography/methods ; Reproducibility of Results ; Tomography, X-Ray Computed/methods ; Young Adult ; }, abstract = {INTRODUCTION: Acetabular cup version is crucial for successful total hip arthroplasty (THA). Many methods have been described for measurement of cup version angle. The aim of this study is to assess the accuracy of five commonly used methods for measurement of acetabular cup version in plain antero-posterior views of the pelvis and hip.

MATERIAL AND METHODS: Sixty primary THA cases were subjected postoperatively to plain A-P of the pelvis (AP-P), A-P view of the hip (AP-H), and computed tomography (CT) imaging. The acetabular cup version was measured in AP-P and AP-H by five methods (Lewinnek, Widmer, Hassan et al., Ackland et al., and Liaw et al.). These measurements were compared to the CT measurement.

RESULTS: All plain X-ray methods showed no significant differences from the CT, except those of Hassan et al. in AP-H, and Widmer and Ackland et al. in AP-P.

For measurement of acetabular cup version angle, we recommend the use of Lewinnek and Liaw et al. methods both in AP-P and in AP-H, while Hassan et al.'s method is recommended in AP-P only, and Widmer and Ackland et al.'s methods in AP-H only.}, } @article {pmid29859776, year = {2018}, author = {Hetherington, MM and Rolls, BJ}, title = {Favouring more rigour when investigating human eating behaviour is like supporting motherhood and apple pie: A response to Robinson, Bevelander, Field, and Jones (2018).}, journal = {Appetite}, volume = {130}, number = {}, pages = {330-333}, doi = {10.1016/j.appet.2018.05.013}, pmid = {29859776}, issn = {1095-8304}, mesh = {*Eating ; *Feeding Behavior ; Humans ; }, abstract = {In a 1987 paper, addressing questions about factors that influence the initiation, maintenance, and termination of food intake, we wrote, "development of systematic procedures to measure eating behaviour is essential if descriptive and inferential statistics are to be applied to answering such questions, giving them power and replicability" (Hetherington & Rolls, 1987 page 77). Therefore, as longstanding advocates of rigorous procedures in laboratory-based investigations of food intake, we welcome Robinson et al.'s (2018) clear recommendations for laboratory studies. However, this is akin to voting for "motherhood and apple pie", and few would argue against deployment of improved procedures for these studies. What then can we contribute to the debate in order to refine the recommendations made or add to them? Our most important message for researchers is that the central hypothesis or main research question will determine the most appropriate methods for any study. If a laboratory-based study is planned, then there are basic methodological questions that must be answered before proceeding to a final protocol. While such guidelines are needed to ensure basic methodological rigour, these should not be so prescriptive as to inhibit creativity. Here we provide several thoughts on how to advance studies of ingestive behaviour, including the need to apply appropriate controls, encouragement to move beyond convenience samples, and to remember the value of exploratory, observational, and naturalistic studies to complement laboratory-based studies.}, } @article {pmid29843378, year = {2018}, author = {Chavanne, X and Bruère, A and Frangi, JP}, title = {Comments to: A Novel Low-Cost Instrumentation System for Measuring the Water Content and Apparent Electrical Conductivity of Soils, Sensors, 15, 25546[-]25563.}, journal = {Sensors (Basel, Switzerland)}, volume = {18}, number = {6}, pages = {}, pmid = {29843378}, issn = {1424-8220}, abstract = {The article comments on claims made by Rêgo et al. about the sensor they developed to determine soil water content and its salinity via the admittance measurement of electrodes embedded in the soil. Their sensor is not based on a self-balanced bridge, as stated, but on a more common technique relying on Ohm's law. A bridge is a zero method of measurement which can provide direct voltages proportional to soil permittivity and conductivity with a high resolution. Thanks to modern electronics the method can be adapted for fast and continuous monitoring in a remote site. Because of this confusion about the different measurement techniques among available admittance or capacitance sensors, we give a succinct review of them and indicate how they compare to the two techniques under discussion. We also question the ability of Rêgo et al.'s current sensor to determine both soil water content and salinity due first to instrument biases and then to the soil complexity as a dielectric medium. In particular, the choice of sensor frequencies is crucial in the two steps. In addition, the procedure to determine and account for temperature influences on readings is not presented clearly enough. It is important to distinguish between the effect resulting from electronics sensitivity, and those that are soil-specific. The comment does not invalidate the design of the sensor, but indicates points, especially parasitic contributions, which must be dealt with to avoid major errors.}, } @article {pmid29808712, year = {2019}, author = {Chen, SN and Riner, ME and Stocker, JF and Hsu, MT}, title = {Uses and Perspectives of Aging Well Terminology in Taiwanese and International Literature: A Systematic Review.}, journal = {Journal of transcultural nursing : official journal of the Transcultural Nursing Society}, volume = {30}, number = {1}, pages = {64-74}, doi = {10.1177/1043659618776353}, pmid = {29808712}, issn = {1552-7832}, mesh = {Healthy Aging/*psychology ; Humans ; *Literature ; *Terminology as Topic ; }, abstract = {The aim of this study is to examine aging well (AW) terminology in Taiwan in its local and global contexts, and to suggest ways of communication by Taiwanese professionals that is sensitive to the lay public's preferences. Researchers conducted a systematic review using Khan et al.'s strategy, and Harden and Thomas' method, to sift through seven databases and synthesize diverse studies on AW. Primary aging well terms used in English and Chinese, their usage frequency in Taiwanese academia, and one term uniquely used by lay people in Taiwan were identified. The synthesized literature illustrated commonality as well as diversity in use and interpretation of aging well terms within Taiwanese society and compared with the Western-based research. More qualitative research is needed to explore how AW is experienced, interpreted, and expected from lay perspectives in Taiwan and other countries have primarily relied on translation and adaptation of Western terms in their scientific research.}, } @article {pmid29802646, year = {2018}, author = {Oppenheim, G and Wu, YJ and Thierry, G}, title = {Found in Translation: Late Bilinguals Do Automatically Activate Their Native Language When They Are Not Using It.}, journal = {Cognitive science}, volume = {}, number = {}, pages = {}, doi = {10.1111/cogs.12618}, pmid = {29802646}, issn = {1551-6709}, abstract = {In their paper "Do Bilinguals Automatically Activate Their Native Language When They Are Not Using it?", Costa, Pannunzi, Deco, and Pickering (Cognitive Science, 2017) proposed a reinterpretation of Thierry and Wu's (2004, 2007) finding of native language-based (Chinese, L1) ERP effects when they tested Chinese-English late bilinguals exclusively in their second language (English, L2). Using simulations in a six-node Hebbian learning model (three L1 nodes, three L2 nodes), Costa et al. suggested that form overlaps in L1 between otherwise unrelated words create a persistent relationship between their L2 translations. In this scenario, words in the nascent L2 lexicon overlapping in their L1 translations would become linked during learning because of the form overlap in L1; once the L2 words are learned, the direct link between them would be sufficient to generate robust, apparently "L1-mediated" priming without requiring any activation of L1 translations. Costa et al. contend that links between L2 words remain beyond the learning phase, even after links to L1 representations have been severed, and thus that their model affords an alternative account to (but not a rebuttal of) Thierry and Wu's claim of language non-selective activation-or automatic activation of translation equivalents-in late bilinguals. In this response, we build on Costa et al.'s original simulation code, showing that it can only reproduce L1-independent priming when implementing the L1 disconnection in their particular way. By contrast, when severing inter-language connections bidirectionally, their model fails to retain any sizeable influence of L1 form overlap on L2 activations. The model is not the theory, however, and we discuss several issues that would need to be addressed in further attempts to model language non-selective activation in late bilinguals.}, } @article {pmid29802425, year = {2018}, author = {Zeukeng, MJ and Seoane-Vazquez, E and Bonnabry, P}, title = {Response to the letter to the Editor regarding Zeukeng et al.'s article A comparison of new drugs approved by the FDA, the EMA, and Swissmedic: an assessment of the international harmonization of drugs.}, journal = {European journal of clinical pharmacology}, volume = {74}, number = {9}, pages = {1199-1200}, pmid = {29802425}, issn = {1432-1041}, mesh = {*Drug Approval ; United States ; United States Food and Drug Administration ; }, } @article {pmid29787718, year = {2018}, author = {Scheel, AM and Ritchie, SJ and Brown, NJL and Jacques, SL}, title = {Methodological problems in a study of fetal visual perception.}, journal = {Current biology : CB}, volume = {28}, number = {10}, pages = {R594-R596}, doi = {10.1016/j.cub.2018.03.047}, pmid = {29787718}, issn = {1879-0445}, mesh = {Female ; *Fetus ; Humans ; Pregnancy ; Pregnancy Trimester, Third ; *Visual Perception ; }, abstract = {Reid et al.[1] analysed data from 39 third-trimester fetuses, concluding that they showed a preferential head-orienting reaction towards lights projected through the uterine wall in a face-like arrangement, as opposed to an inverted triangle of dots. These results imply not only that assessment of visual-perceptive responses is possible in prenatal subjects, but also that a measurable preference for faces exists before birth. However, we have identified three substantial problems with Reid et al.'s [1] method and analyses, which we outline here.}, } @article {pmid29782031, year = {2018}, author = {Müderrisoglu, A and Babaoglu, M}, title = {Letter to the Editor regarding Hubacek et al.'s report "Lack of an association between SNPs within the cholinergic receptor genes and smoking behavior in a Czech post-MONICA study".}, journal = {Genetics and molecular biology}, volume = {41}, number = {2}, pages = {417-418}, pmid = {29782031}, issn = {1415-4757}, } @article {pmid29780877, year = {2018}, author = {Nitta, H and Tomita, H and Zhang, Y and Zhou, X and Yamada, Y}, title = {Disgust and the rubber hand illusion: a registered replication report of Jalal, Krishnakumar, and Ramachandran (2015).}, journal = {Cognitive research: principles and implications}, volume = {3}, number = {1}, pages = {15}, pmid = {29780877}, issn = {2365-7464}, abstract = {Heightened experience of disgust is a feature of obsessive-compulsive disorder (OCD), particularly contamination-related OCD (C-OCD). Previous studies of the rubber hand illusion (RHI) reported that the sense of body ownership is related to the interaction between vision, touch, and proprioception. One recent study demonstrated a link between the RHI and disgust, suggesting that there is an interaction between these three perceptual modalities and disgust (Jalal et al., PLOS ONE 10:e0139159, 2015). However, there have been no direct replications of this initial study. We therefore performed a direct replication of Jalal et al.'s (PLOS ONE 10:e0139159, 2015) study. We examined 133 participants (based on a power analysis) to determine whether placing contamination-related stimuli on a rubber hand causes OCD-like disgust among healthy participants experiencing the RHI. That is, we tested whether Japanese participants experience more intense disgust when the rubber hand and the participant's hidden hand are stroked synchronously than when stroked asynchronously, in order to replicate and examine the cross-cultural validity of this effect. The main finding of the original study by Jalal and colleagues was successfully replicated in a large sample. Some inconsistencies in one of the control procedures exploring coldness sensations during the RHI were found, which could possibly be due to cross-cultural differences or the improved statistical power of the present study. Based on the present replication study, we conclude that an intervention using the RHI as proposed by Jalal et al. (PLOS ONE 10:e0139159, 2015) might potentially be useful for the treatment of OCD following replications in clinical OCD populations. Preregistration details: This study was preregistered with Cognitive Research: Principles and Implications. The Authors' protocol received in-principle acceptance on 31 March 2017. The preregistered protocol is available here: 10.6084/m9.figshare.6217295.}, } @article {pmid29777983, year = {2018}, author = {Sundara, M and Ngon, C and Skoruppa, K and Feldman, NH and Onario, GM and Morgan, JL and Peperkamp, S}, title = {Young infants' discrimination of subtle phonetic contrasts.}, journal = {Cognition}, volume = {178}, number = {}, pages = {57-66}, pmid = {29777983}, issn = {1873-7838}, support = {R01 HD032005/HD/NICHD NIH HHS/United States ; R01 HD068501/HD/NICHD NIH HHS/United States ; }, mesh = {Acoustic Stimulation ; *Discrimination Learning ; Female ; Humans ; Infant ; Language Development ; Male ; *Phonetics ; Speech Acoustics ; *Speech Perception ; }, abstract = {It is generally accepted that infants initially discriminate native and non-native contrasts and that perceptual reorganization within the first year of life results in decreased discrimination of non-native contrasts, and improved discrimination of native contrasts. However, recent findings from Narayan, Werker, and Beddor (2010) surprisingly suggested that some acoustically subtle native-language contrasts might not be discriminated until the end of the first year of life. We first provide countervailing evidence that young English-learning infants can discriminate the Filipino contrast tested by Narayan et al. when tested in a more sensitive paradigm. Next, we show that young infants learning either English or French can also discriminate comparably subtle non-native contrasts from Tamil. These findings show that Narayan et al.'s null findings were due to methodological choices and indicate that young infants are sensitive to even subtle acoustic contrasts that cue phonetic distinctions cross-linguistically. Based on experimental results and acoustic analyses, we argue that instead of specific acoustic metrics, infant discrimination results themselves are the most informative about the salience of phonetic distinctions.}, } @article {pmid29769356, year = {2018}, author = {Esser, HJ and Hartemink, NA and de Boer, WF}, title = {Comment on Titcomb et al.'s 'Interacting effects of wildlife loss and climate on ticks and tick-borne disease'.}, journal = {Proceedings. Biological sciences}, volume = {285}, number = {1878}, pages = {}, pmid = {29769356}, issn = {1471-2954}, mesh = {Animals ; Animals, Wild ; Climate ; *Tick-Borne Diseases ; *Ticks ; }, } @article {pmid29769159, year = {2019}, author = {de Zwart, PL and Jeronimus, BF and de Jonge, P}, title = {Empirical evidence for definitions of episode, remission, recovery, relapse and recurrence in depression: a systematic review.}, journal = {Epidemiology and psychiatric sciences}, volume = {28}, number = {5}, pages = {544-562}, pmid = {29769159}, issn = {2045-7979}, mesh = {Adult ; Antidepressive Agents/therapeutic use ; Depression/*diagnosis/drug therapy/*psychology ; Depressive Disorder/*diagnosis/drug therapy/*psychology ; Evidence-Based Practice ; Humans ; Outcome Assessment, Health Care ; Psychiatric Status Rating Scales ; Recurrence ; Remission Induction ; }, abstract = {AIMS.: For the past quarter of a century, Frank et al.'s (1991) consensus-based definitions of major depressive disorder (MDD) episode, remission, recovery, relapse and recurrence have been the paramount driving forces for consistency in MDD research as well as in clinical practice. This study aims to review the evidence for the empirical validation of Frank et al.'s proposed concept definitions and to discuss evidence-based modifications.

METHODS.: A literature search of Web of Science and PubMed from 1/1/1991 to 08/30/2017 identified all publications which referenced Frank et al.'s request for definition validation. Publications with data relevant for validation were included and checked for referencing other studies providing such data.

RESULTS.: A total of 56 studies involving 39 315 subjects were included, mainly presenting data to validate the severity and duration thresholds for defining remission and recovery. Most studies indicated that the severity threshold for defining remission should decrease. Additionally, specific duration thresholds to separate remission from recovery did not add any predictive value to the notion that increased remission duration alleviates the risk of reoccurrence of depressive symptoms. Only limited data were available to validate the severity and duration criteria for defining a depressive episode.

CONCLUSIONS.: Remission can best be defined as a less symptomatic state than previously assumed (Hamilton Rating Scale for Depression, 17-item version (HAMD-17) ⩽4 instead of ⩽7), without applying a duration criterion. Duration thresholds to separate remission from recovery are not meaningful. The minimal duration of depressive symptoms to define a depressive episode should be longer than 2 weeks, although further studies are required to recommend an exact duration threshold. These results are relevant for researchers and clinicians aiming to use evidence-based depression outcomes.}, } @article {pmid29768089, year = {2018}, author = {Shellington, EM and Reichert, SM and Petrella, RJ}, title = {Commentary on: "Effects of Regular Physical Activity on the Cognitive Performance of Type 2 Diabetic Patients: A Systematic Review" by Podolski et al. (Metab Syndr Relat Disord 2017;15:481-493).}, journal = {Metabolic syndrome and related disorders}, volume = {16}, number = {6}, pages = {255-261}, doi = {10.1089/met.2018.0021}, pmid = {29768089}, issn = {1557-8518}, mesh = {Aged ; Cognition ; Cognitive Dysfunction ; *Diabetes Mellitus, Type 2 ; Exercise ; *Glycated Hemoglobin ; Humans ; }, abstract = {Type 2 diabetes mellitus (T2DM) imparts an increased risk for cognitive decline, specifically executive function, which is important to maintain for diabetes self-management. There is evidence to suggest that exercise improves cognition in healthy older adults; however, the literature in adults with T2DM is lacking. This commentary is in complement to Podolski et al.'s systematic review evaluating the effects of physical activity on cognitive function in adults with T2DM. We have included eight additional studies and further highlight their conclusions on the heterogeneity of the literature thus far. Three current issues with the literature are as follows: (1) variability in interventions (e.g., aerobic, resistance, lifestyle, and yoga), (2) variability in cognitive outcome measures, and (3) lack of detailed description of the population studied, for example, baseline glycated hemoglobin (A1C) values. Overall, making it difficult to compare these studies and draw final conclusions. Thus, the efficacy for exercise to improve cognition in adults with T2DM is not yet well understood. Potential ways to mitigate these limitations could be for future studies that (1) use robust methodology whenever possible, that is, randomized controlled trials, (2) to follow current guideline-derived exercise recommendations for adults with T2DM, and (3) utilize cognitive outcome measures that are consistent across studies. The hope is that these consistencies in turn will help to determine the efficacy of exercise on cognitive function in adults with T2DM and therefore, allow national organizations to develop recommendations and guidelines for healthcare practitioners to follow.}, } @article {pmid29766288, year = {2018}, author = {Albakri, A and Watson, KM}, title = {Letter to the editor regarding Pluymen et al.'s paper: Early introduction of complementary foods and childhood overweight in breastfed and formula-fed infants in the Netherlands: the PIAMA birth cohort study.}, journal = {European journal of nutrition}, volume = {57}, number = {5}, pages = {1995-1996}, pmid = {29766288}, issn = {1436-6215}, mesh = {Breast Feeding ; Child ; Cohort Studies ; Humans ; Infant ; Infant Formula ; Netherlands ; *Pediatric Obesity ; }, } @article {pmid29755840, year = {2018}, author = {Liu, Z and Ma, K and Huang, D}, title = {Treatment of mallet finger deformity with a modified palmaris longus tendon graft through a bone tunnel.}, journal = {International journal of burns and trauma}, volume = {8}, number = {2}, pages = {34-39}, pmid = {29755840}, issn = {2160-2026}, abstract = {OBJECTIVE: To investigate the clinical effect of treating mallet finger deformity using a modified palmaris longus tendon graft through a bone tunnel.

METHODS: Altogether, 21 patients with mallet finger deformity (16 men, 5 women; average age 31 years, range 19-47 years) were treated with a modified palmaris longus tendon graft through a bone tunnel during 18 months (2014-2016). Four index fingers, seven middle fingers, eight ring fingers, and two little fingers were treated for four cutting injuries, eleven finger sprains, four crush injuries, and two twist injuries (7 open and 14 closed injuries). Duration from injury to surgery was 9 h to 13 weeks. Three patients underwent surgery after 6 weeks of unsuccessful conservative treatment. No tendon was attached to the extensor tendon insertion in 16 patients, and 5 had residual tendon of <0.2 cm attached. All patients had distal segment flexion deformity and dorsiflexion disorder. Surgery comprised transverse penetration and vertical drilling of the base of the distal phalanx (2.0 and 2.5 mm diameter drills). Equal shallow semitendinosus pieces of the palmaris longus tendon (4 cm) were obtained from the sagittal end and were passed through a dorsal bone hole, emerging from a transverse bone hole. The two bundles were sutured to the main tendon. Tension was adjusted, and the broken ends were sutured. The distal interphalangeal joints were fixed in hyperextension.

RESULTS: All patients were followed for 7-16 months (average 6.0 ± 0.3 months) postoperatively. All 21 patients had grade A wound healing, with no complications (e.g., necrotic wound, recurrence, joint stiffness). The mallet finger deformity was corrected with good appearance, no obvious abnormalities, and satisfactory flexion and extension. Two patients had a superficial wound infection. Each recovered after symptomatic treatment. One patient had a mild result, with limited extension. There were no recurrences. Results were evaluated according to Patel et al.'s system, which revealed 15 excellent and 5 good results (combined 95.23% rate), with 1 mild result (limited extension). Patients were satisfied with the appearance and function of the affected fingers, and the desired surgical end result was achieved.

CONCLUSION: Use of this modified surgery for treating mallet finger deformity, especially with no or little tendon attached at the extensor tendon insertion, results in nearly anatomical reconstruction of the extensor tendon insertion. Its advantages include simple surgery, reliable fixation, fewer complications, and clinical efficacy.}, } @article {pmid29751413, year = {2018}, author = {Yu, Q and Wang, HZ and Jeppesen, E and Xu, C and Wang, HJ}, title = {Reply to Cao et al.'s comment on "Does the responses of Vallisneria natans (Lour.) Hara to high nitrogen loading differ between the summer high-growth season and the low-growth season? Science of the Total Environment 601-602 (2017) 1513-1521".}, journal = {The Science of the total environment}, volume = {615}, number = {}, pages = {1093-1094}, doi = {10.1016/j.scitotenv.2017.09.306}, pmid = {29751413}, issn = {1879-1026}, mesh = {Animals ; Catfishes ; Hydrocharitaceae ; Nitrogen/*analysis ; *Seasons ; Water Pollutants, Chemical/analysis ; }, } @article {pmid29746906, year = {2018}, author = {Colclough, GL and Woolrich, MW and Harrison, SJ and Rojas López, PA and Valdes-Sosa, PA and Smith, SM}, title = {Multi-subject hierarchical inverse covariance modelling improves estimation of functional brain networks.}, journal = {NeuroImage}, volume = {178}, number = {}, pages = {370-384}, pmid = {29746906}, issn = {1095-9572}, support = {092753/WT_/Wellcome Trust/United Kingdom ; U54 MH091657/MH/NIMH NIH HHS/United States ; 203139/WT_/Wellcome Trust/United Kingdom ; 1U54MH091657/NH/NIH HHS/United States ; 098369/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Adult ; Algorithms ; Animals ; Bayes Theorem ; Brain/*physiology ; Cats ; Connectome/*methods ; Datasets as Topic ; Female ; Humans ; Image Processing, Computer-Assisted/*methods ; Macaca ; Male ; *Models, Neurological ; Nerve Net/*physiology ; Neural Pathways/physiology ; Young Adult ; }, abstract = {A Bayesian model for sparse, hierarchical, inver-covariance estimation is presented, and applied to multi-subject functional connectivity estimation in the human brain. It enables simultaneous inference of the strength of connectivity between brain regions at both subject and population level, and is applicable to fMRI, MEG and EEG data. Two versions of the model can encourage sparse connectivity, either using continuous priors to suppress irrelevant connections, or using an explicit description of the network structure to estimate the connection probability between each pair of regions. A large evaluation of this model, and thirteen methods that represent the state of the art of inverse covariance modelling, is conducted using both simulated and resting-state functional imaging datasets. Our novel Bayesian approach has similar performance to the best extant alternative, Ng et al.'s Sparse Group Gaussian Graphical Model algorithm, which also is based on a hierarchical structure. Using data from the Human Connectome Project, we show that these hierarchical models are able to reduce the measurement error in MEG beta-band functional networks by 10%, producing concomitant increases in estimates of the genetic influence on functional connectivity.}, } @article {pmid29746176, year = {2019}, author = {Christensen, AP and Cotter, KN and Silvia, PJ}, title = {Reopening Openness to Experience: A Network Analysis of Four Openness to Experience Inventories.}, journal = {Journal of personality assessment}, volume = {101}, number = {6}, pages = {574-588}, doi = {10.1080/00223891.2018.1467428}, pmid = {29746176}, issn = {1532-7752}, mesh = {Adult ; *Cognition ; Exploratory Behavior ; Fantasy ; Female ; Humans ; *Intelligence ; Male ; *Personality ; Personality Inventory/*standards ; Self-Assessment ; }, abstract = {Openness to Experience is a complex trait, the taxonomic structure of which has been widely debated. Previous research has provided greater clarity of its lower order structure by synthesizing facets across several scales related to Openness to Experience. In this study, we take a finer grained approach by investigating the item-level relations of four Openness to Experience inventories (Big Five Aspects Scale, HEXACO-100, NEO PI-3, and Woo et al.'s Openness to Experience Inventory), using a network science approach, which allowed items to form an emergent taxonomy of facets and aspects. Our results (N = 802) identified 10 distinct facets (variety-seeking, aesthetic appreciation, intellectual curiosity, diversity, openness to emotions, fantasy, imaginative, self-assessed intelligence, intellectual interests, and nontraditionalism) that largely replicate previous findings as well as three higher order aspects: two that are commonly found in the literature (intellect and experiencing; i.e., openness), and one novel aspect (open-mindedness). In addition, we demonstrate that each Openness to Experience inventory offers a unique conceptualization of the trait, and that some inventories provide broader coverage of the network space than others. Our findings establish a broader consensus of Openness to Experience at the aspect and facet level, which has important implications for researchers and the Openness to Experience inventories they use.}, } @article {pmid29742962, year = {2018}, author = {Turcotte, V and Gagnon, ME and Joubert, S and Rouleau, I and Gagnon, JF and Escudier, F and Koski, L and Potvin, O and Macoir, J and Hudon, C}, title = {Normative data for the Clock Drawing Test for French-Quebec mid- and older aged healthy adults.}, journal = {The Clinical neuropsychologist}, volume = {32}, number = {sup1}, pages = {91-101}, doi = {10.1080/13854046.2018.1473495}, pmid = {29742962}, issn = {1744-4144}, support = {//CIHR/Canada ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Canada ; Cognitive Dysfunction/*diagnosis ; Female ; Healthy Volunteers ; Humans ; Language ; Male ; Mass Screening ; Middle Aged ; *Neuropsychological Tests ; Observer Variation ; Quebec ; Reference Values ; }, abstract = {OBJECTIVE: The Clock Drawing Test (CDT) is frequently used to screen for cognitive impairment, however, normative data for Rouleau et al.'s scoring system are scarce. The present study aims to provide norms for Rouleau et al.'s scoring system that are tailored to Quebec French-speaking mid- and older aged healthy adults.

METHODS: Six researchers from various research centers across the Province of Quebec (Canada) sent anonymous data for 593 (391 women) healthy community-dwelling volunteers (age range: 43-93 years; education range: 5-23 years) who completed the CDT 'drawing on command' version. This command version (setting the clock hands to 11:10, without a pre-drawn circle) was administrated as part of a more extensive neuropsychological assessment, or along with cognitive screening instruments. Each drawn clock was scored according to the quantitative criteria set by Rouleau et al.'s scoring system.

RESULTS: CDT scores were significantly correlated with age (r(592) = -.132, p = .001) and years of education (r(592) = .116, p = .005), but not with sex (r(592) = .065, p = .112). Since data were skewed towards higher test scores, the percentiles method was used for analysis. Percentile ranks stratified by age and education are presented.

CONCLUSION: These normative data for Rouleau et al.'s scoring system will contribute towards adequately screening for cognitive decline in Quebec French-speaking healthy adults, by also taking into account individual characteristics such as age and education.}, } @article {pmid29739754, year = {2018}, author = {Panch, SR and Bozik, ME and Brown, T and Makiya, M and Prussin, C and Archibald, DG and Hebrank, GT and Sullivan, M and Sun, X and Wetzler, L and Ware, J and Fay, MP and Dunbar, CE and Dworetzky, SI and Khoury, P and Maric, I and Klion, AD}, title = {Dexpramipexole as an oral steroid-sparing agent in hypereosinophilic syndromes.}, journal = {Blood}, volume = {132}, number = {5}, pages = {501-509}, pmid = {29739754}, issn = {1528-0020}, mesh = {Administration, Oral ; Adult ; Aged ; Antioxidants/*administration & dosage ; Eosinophils/*drug effects ; Female ; Follow-Up Studies ; Humans ; Hypereosinophilic Syndrome/*drug therapy/pathology ; Male ; Middle Aged ; Pramipexole/*administration & dosage ; Prognosis ; Safety ; *Steroids ; }, abstract = {Hypereosinophilic syndromes (HESs) are a heterogeneous group of disorders characterized by peripheral eosinophilia and eosinophil-related end organ damage. Whereas most patients respond to glucocorticoid (GC) therapy, high doses are often necessary, and side effects are common. Dexpramipexole (KNS-760704), an orally bioavailable synthetic aminobenzothiazole, showed an excellent safety profile and was coincidentally noted to significantly decrease absolute eosinophil counts (AECs) in a phase 3 trial for amyotrophic lateral sclerosis. This proof-of-concept study was designed to evaluate dexpramipexole (150 mg orally twice daily) as a GC-sparing agent in HESs. Dual primary end points were (1) the proportion of subjects with ≥50% decrease in the minimum effective GC dose (MED) to maintain AEC <1000/μL and control clinical symptoms, and (2) the MED after 12 weeks of dexpramipexole (MEDD) as a percentage of the MED at week 0. Out of 10 subjects, 40% (95% confidence interval [CI], 12%, 74%) achieved a ≥50% reduction in MED, and the MEDD/MED ratio was significantly <100% (median, 66%; 95% CI, 6%, 98%; P = .03). All adverse events were self-limited, and none led to drug discontinuation. Affected tissue biopsy samples in 2 subjects showed normalization of pathology and depletion of eosinophils on dexpramipexole. Bone marrow biopsy samples after 12 weeks of dexpramipexole showed selective absence of mature eosinophils in responders. Dexpramipexole appears promising as a GC-sparing agent without apparent toxicity in a subset of subjects with GC-responsive HESs. Although the exact mechanism of action is unknown, preliminary data suggest that dexpramipexole may affect eosinophil maturation in the bone marrow. This study was registered at www.clinicaltrials.gov as #NCT02101138.}, } @article {pmid29727658, year = {2018}, author = {Pi, C and Yuan, J and Liu, H and Zuo, Y and Feng, T and Zhan, C and Wu, J and Ye, Y and Zhao, L and Wei, Y}, title = {In vitro and in vivo evaluation of curcumin loaded hollow microspheres prepared with ethyl cellulose and citric acid.}, journal = {International journal of biological macromolecules}, volume = {115}, number = {}, pages = {1046-1054}, doi = {10.1016/j.ijbiomac.2018.04.171}, pmid = {29727658}, issn = {1879-0003}, mesh = {Animals ; Biological Availability ; Cellulose/*analogs & derivatives/chemistry ; Citric Acid/*chemistry ; Curcumin/*chemistry/pharmacokinetics ; Diffusion ; Drug Carriers/*chemistry ; Drug Liberation ; *Microspheres ; Rats ; Rats, Sprague-Dawley ; Solvents/chemistry ; }, abstract = {Curcumin (CUR) demonstrates a variety of biological activities; however, the poor oral bioavailability limits its clinical application. The objective of this study was to develop and evaluate characteristics and bioavailability of hollow microspheres loading curcumin (CUR-HPs). CUR-HPs were prepared by solvent diffusion and evaporation method. The effect of viscosity of ethyl cellulose (EC), amount of EC, citric acid (CA) and CUR on physicochemical characteristics and in vitro release profile of CUR-HPs were evaluated. Scanning electron microscopy (SEM) showed microspheres had smooth surfaces with hollow structures. The yield of CUR-HPs was (96 ± 1.80) %. The floating rate at 24 h was (89.67 ± 4.91) % and the drug loading was (3.41 ± 0.21) %. Nearly 95% of CUR was released from the HPs at 24 h. In vitro release profiles of CUR-HPs fitted the Korsmeyer et al.'s equation and indicated that CUR was released through the combination of diffusion and erosion mechanisms. The bioavailability of CUR-HPs was 12-fold higher than that of CUR. The peak time was delayed for 7.5 h and peak concentration of CUR-HPs was 3.21 times than that of free CUR. The CUR-HPs might be a promising strategy to achieve sustained release and increase oral bioavailability of CUR.}, } @article {pmid29723710, year = {2018}, author = {Ruby, E and Maniscalco, B and Peters, MAK}, title = {On a 'failed' attempt to manipulate visual metacognition with transcranial magnetic stimulation to prefrontal cortex.}, journal = {Consciousness and cognition}, volume = {62}, number = {}, pages = {34-41}, pmid = {29723710}, issn = {1090-2376}, support = {R01 NS088628/NS/NINDS NIH HHS/United States ; }, mesh = {Humans ; Metacognition/*physiology ; Prefrontal Cortex/*physiology ; Signal Detection, Psychological ; *Transcranial Magnetic Stimulation ; Visual Perception/*physiology ; }, abstract = {Rounis, Maniscalco, Rothwell, Passingham, and Lau (2010) reported that stimulation of prefrontal cortex impairs visual metacognition. Bor, Schwartzman, Barrett, and Seth (2017) attempted to replicate this result, but adopted an experimental design that reduced their chanceof obtaining positive findings. Despite that, their results appeared initially consistent with those of Rounis et al., but they subsequently claimed it was necessary to discard ∼30% of their subjects, after which they reported a null result. Using computer simulations, we found that, contrary to their supposed purpose, excluding subjects by Bor et al.'s criteria does not reduce false positive rates. Including both their positive and negative result in a Bayesian framework, we show the correct interpretation is that PFC stimulation likely impaired visual metacognition, exactly contradicting Bor et al.'s claims. That lesion and inactivation studies demonstrate similar positive effects further suggests that Bor et al.'s reported negative finding isn't evidence against the role of prefrontal cortex in metacognition.}, } @article {pmid29721291, year = {2018}, author = {Kirk, DA and Park, AC and Smith, AC and Howes, BJ and Prouse, BK and Kyssa, NG and Fairhurst, EN and Prior, KA}, title = {Our use, misuse, and abandonment of a concept: Whither habitat?.}, journal = {Ecology and evolution}, volume = {8}, number = {8}, pages = {4197-4208}, pmid = {29721291}, issn = {2045-7758}, abstract = {The foundational concept of habitat lies at the very root of the entire science of ecology, but inaccurate use of the term compromises scientific rigor and communication among scientists and nonscientists. In 1997, Hall, Krausman & Morrison showed that 'habitat' was used correctly in only 55% of articles. We ask whether use of the term has been more accurate since their plea for standardization and whether use varies across the broader range of journals and taxa in the contemporary literature (1998-2012). We searched contemporary literature for 'habitat' and habitat-related terms, ranking usage as either correct or incorrect, following a simplified version of Hall et al.'s definitions. We used generalized linear models to compare use of the term in contemporary literature with the papers reviewed by Hall et al. and to test the effects of taxa, journal impact in the contemporary articles and effects due to authors that cited Hall et al. Use of the term 'habitat' has not improved; it was still only used correctly about 55% of the time in the contemporary data. Proportionately more correct uses occurred in articles that focused on animals compared to ones that included plants, and papers that cited Hall et al. did use the term correctly more often. However, journal impact had no effect. Some habitat terms are more likely to be misused than others, notably 'habitat type', usually used to refer to vegetation type, and 'suitable habitat' or 'unsuitable habitat', which are either redundant or nonsensical by definition. Inaccurate and inconsistent use of the term can lead to (1) misinterpretation of scientific findings; (2) inefficient use of conservation resources; (3) ineffective identification and prioritization of protected areas; (4) limited comparability among studies; and (5) miscommunication of science-based findings. Correct usage would improve communication with scientists and nonscientists, thereby benefiting conservation efforts, and ecology as a science.}, } @article {pmid29716452, year = {2018}, author = {Wade, KA and Nash, RA and Lindsay, DS}, title = {Reasons to Doubt the Reliability of Eyewitness Memory: Commentary on Wixted, Mickes, and Fisher (2018).}, journal = {Perspectives on psychological science : a journal of the Association for Psychological Science}, volume = {13}, number = {3}, pages = {339-342}, doi = {10.1177/1745691618758261}, pmid = {29716452}, issn = {1745-6924}, mesh = {Crime ; Emotions ; Humans ; *Memory ; *Mental Recall ; Reproducibility of Results ; }, abstract = {Wixted, Mickes, and Fisher (this issue) take issue with the common trope that eyewitness memory is inherently unreliable. They draw on a large body of mock-crime research and a small number of field studies, which indicate that high-confidence eyewitness reports are usually accurate, at least when memory is uncontaminated and suitable interviewing procedures are used. We agree with the thrust of Wixted et al.'s argument and welcome their invitation to confront the mass underselling of eyewitnesses' potential reliability. Nevertheless, we argue that there is a comparable risk of overselling eyewitnesses' reliability. Wixted et al.'s reasoning implies that near-pristine conditions or uncontaminated memories are normative, but there are at least two good reasons to doubt this. First, psychological science does not yet offer a good understanding of how often and when eyewitness interviews might deviate from best practice in ways that compromise the accuracy of witnesses' reports. Second, witnesses may frequently be exposed to preinterview influences that could corrupt reports obtained in best-practice interviews.}, } @article {pmid29702675, year = {2018}, author = {Baig, AF and Hassan, KMU and Ghani, A and Chaudhry, SA and Khan, I and Ashraf, MU}, title = {A lightweight and secure two factor anonymous authentication protocol for Global Mobility Networks.}, journal = {PloS one}, volume = {13}, number = {4}, pages = {e0196061}, pmid = {29702675}, issn = {1932-6203}, mesh = {Algorithms ; *Computer Security ; Information Systems ; *Privacy ; *Wireless Technology ; }, abstract = {Global Mobility Networks(GLOMONETs) in wireless communication permits the global roaming services that enable a user to leverage the mobile services in any foreign country. Technological growth in wireless communication is also accompanied by new security threats and challenges. A threat-proof authentication protocol in wireless communication may overcome the security flaws by allowing only legitimate users to access a particular service. Recently, Lee et al. found Mun et al. scheme vulnerable to different attacks and proposed an advanced secure scheme to overcome the security flaws. However, this article points out that Lee et al. scheme lacks user anonymity, inefficient user authentication, vulnerable to replay and DoS attacks and Lack of local password verification. Furthermore, this article presents a more robust anonymous authentication scheme to handle the threats and challenges found in Lee et al.'s protocol. The proposed protocol is formally verified with an automated tool(ProVerif). The proposed protocol has superior efficiency in comparison to the existing protocols.}, } @article {pmid29702439, year = {2018}, author = {Huang, HM and Huang, CY and Lee-Hsieh, J and Cheng, SF}, title = {Establishing the competences of clinical reasoning for nursing students in Taiwan: From the nurse educators' perspectives.}, journal = {Nurse education today}, volume = {66}, number = {}, pages = {110-116}, doi = {10.1016/j.nedt.2018.04.007}, pmid = {29702439}, issn = {1532-2793}, mesh = {Adult ; *Clinical Competence ; Curriculum ; Education, Nursing, Baccalaureate ; Faculty, Nursing/*psychology ; Female ; Humans ; Interviews as Topic ; Middle Aged ; *Problem Solving ; Qualitative Research ; *Students, Nursing ; Taiwan ; }, abstract = {BACKGROUND: Clinical reasoning is an essential core competence for nurses. Maintaining quality of care and safety of patients results from cultivation of student's clinical reasoning competency. However, the concept of clinical reasoning in nursing students is complex and its meaning and process needs further clarification.

OBJECTIVES: The objectives were to explore the meaning of clinical reasoning competency in Taiwanese nursing students and to operationalize the concept in order to structure a framework illustrating the process of clinical reasoning.

SETTING AND PARTICIPANTS: Thirteen seasoned nursing experts who had more than ten years of experience in nursing education or clinical practice participated in the interviews. The interviews were conducted in settings that the participants perceived as convenient, quiet and free of disturbance.

METHODS: Semi-structured interviews were conducted. The interviews were audio-recorded and field notes were taken. The data were analyzed using Waltz et al.'s (2010) method of content analysis.

RESULTS: The data revealed four domains and 11 competency indicators. The four domains include: awareness of clinical cues, confirmation of clinical problems, determination and implementation of actions, and evaluation and self-reflection. Each domain comprises of 2-4 indicators of clinical reasoning competency. In addition, this study established a framework for cultivation of clinical reasoning competency in nursing students.

CONCLUSION: The indicators of clinical reasoning competency in nursing students are interwoven, interactive and interdependent to form a dynamic process. The findings of this study may facilitate evaluation of nursing students' clinical reasoning competency and development of instruments to assess clinical reasoning in nursing students.}, } @article {pmid29683722, year = {2018}, author = {Stegmann, G and Jacobucci, R and Serang, S and Grimm, KJ}, title = {Recursive Partitioning with Nonlinear Models of Change.}, journal = {Multivariate behavioral research}, volume = {53}, number = {4}, pages = {559-570}, doi = {10.1080/00273171.2018.1461602}, pmid = {29683722}, issn = {1532-7906}, mesh = {Academic Success ; Child ; *Data Interpretation, Statistical ; Humans ; Linear Models ; Longitudinal Studies ; *Nonlinear Dynamics ; Reading ; Software ; }, abstract = {In this article, we introduce nonlinear longitudinal recursive partitioning (nLRP) and the R package longRpart2 to carry out the analysis. This method implements recursive partitioning (also known as decision trees) in order to split data based on individual- (i.e., cluster) level covariates with the goal of predicting differences in nonlinear longitudinal trajectories. At each node, a user-specified linear or nonlinear mixed-effects model is estimated. This method is an extension of Abdolell et al.'s (2002) longitudinal recursive partitioning while permitting a nonlinear mixed-effects model in addition to a linear mixed-effects model in each node. We give an overview of recursive partitioning, nonlinear mixed-effects models for longitudinal data, describe nLRP, and illustrate its use with empirical data from the Early Childhood Longitudinal Study-Kindergarten Cohort.}, } @article {pmid29661605, year = {2018}, author = {Kobyliak, N and Falalyeyeva, T and Mykhalchyshyn, G and Kyriienko, D and Komissarenko, I}, title = {Effect of alive probiotic on insulin resistance in type 2 diabetes patients: Randomized clinical trial.}, journal = {Diabetes & metabolic syndrome}, volume = {12}, number = {5}, pages = {617-624}, doi = {10.1016/j.dsx.2018.04.015}, pmid = {29661605}, issn = {1878-0334}, mesh = {Adolescent ; Adult ; Aged ; Blood Glucose/*metabolism ; Diabetes Mellitus, Type 2/*blood/diagnosis/*diet therapy ; Double-Blind Method ; Female ; Humans ; Insulin Resistance/*physiology ; Male ; Middle Aged ; Probiotics/*administration & dosage ; Young Adult ; }, abstract = {BACKGROUND: Probiotics have beneficial effect on obesity related disorders in animal models. Despite a large number of animal data, randomized placebo-controlled trials (RCT) concluded that probiotics have a moderate effect on glycemic control-related parameters. However, effect of probiotics on insulin resistance are inconsistent.

AIM: In a double-blind single center RCT, effect of alive multistrain probiotic vs. placebo on insulin resistance in type 2 diabetes patient were assessed.

METHODS: A total of 53 patients met the criteria for inclusion. They were randomly assigned to receive multiprobiotic "Symbiter" (concentrated biomass of 14 probiotic bacteria genera Bifidobacterium, Lactobacillus, Lactococcus, Propionibacterium) or placebo for 8-weeks administered as a sachet formulation. The primary main outcome was the change HOMA-IR (homeostasis model assessment-estimated insulin resistance) which calculated using Matthews et al.'s equation. Secondary outcomes were the changes in glycemic control-related parameters, anthropomorphic variables and cytokines.

RESULTS: Supplementation with alive multiprobiotic for 8 weeks was associated with significant reduction of HOMA-IR from 6.85 ± 0.76 to 5.13 ± 0.49 (p = 0.047), but remained static in the placebo group. With respect to our secondary outcomes, HbA1c insignificant decreased by 0.09% (p = 0.383) and 0.24% (p = 0.068) respectively in placebo and probiotics groups. However, in probiotic responders (n = 22, patient with decrease in HOMA-IR) after supplementation a significant reduction in HbA1c by 0.39% (p = 0.022) as compared to non-responders was observed. In addition, from markers of chronic systemic inflammatory state only TNF-α and IL-1β changes significantly after treatment with probiotics.

CONCLUSION: Probiotic therapies modestly improved insulin resistance in patients with type 2 diabetes.}, } @article {pmid29653378, year = {2018}, author = {Clark, KB}, title = {Possible origins of consciousness in simple control over "involuntary" neuroimmunological action.}, journal = {Consciousness and cognition}, volume = {61}, number = {}, pages = {76-78}, doi = {10.1016/j.concog.2018.04.002}, pmid = {29653378}, issn = {1090-2376}, mesh = {Animals ; Autonomic Nervous System/*physiology ; Consciousness/*physiology ; Humans ; Neuroimmunomodulation/*physiology ; }, abstract = {The origin(s) and purpose(s) of consciousness continue to be fervently debated by neuroscientists. A recent unconventional hypothesis put forth by Morsella et al. suggests the primary function of consciousness is the integration, selection, and execution of advantageous lower-level voluntary skeletal muscle behavior on surrounding external environments. However, at main issue is whether more precise, adaptable voluntary skeletal motor action, and therefore the corresponding workings of consciousness, first emerged and evolved in animals to exert control over external environments or internal ones regulated by less flexible autonomic function. Using the example of voluntary immunomodulation, one can identify the strengths and weaknesses of either rationale. For instance, highly trained meditative techniques for immunomodulation more-or-less conform to Morsella et al.'s assumptions on higher-level indirect conscious control of autonomic function. Whereas, untrained skeletal motor resolution of infection-related approach-avoidance conflicts support conclusions contrary to those of Morsella et al. In such cases, primitive voluntary changes in host respiration rate and volume may selectively facilitate/inhibit acute autonomic psychophysiological stress responses to pathogen insult. This and other types of scenarios predictably give evolutionary and ecological rise to self-awareness of (visceral) internal states as well as to voluntary regulation of internal state action conflicts.}, } @article {pmid29651687, year = {2018}, author = {Harrington Stack, CM and James, AN and Watson, DG}, title = {A failure to replicate rapid syntactic adaptation in comprehension.}, journal = {Memory & cognition}, volume = {46}, number = {6}, pages = {864-877}, pmid = {29651687}, issn = {1532-5946}, mesh = {Adaptation, Physiological/*physiology ; Adult ; Comprehension/*physiology ; Humans ; *Psycholinguistics ; *Reading ; Young Adult ; }, abstract = {Language comprehension requires successfully navigating linguistic variability. One hypothesis for how listeners manage variability is that they rapidly update their expectations of likely linguistic events in new contexts. This process, called adaptation, allows listeners to better predict the upcoming linguistic input. In previous work, Fine, Jaeger, Farmer, and Qian (PLoS ONE, 8, e77661, 2013) found evidence for syntactic adaptation. Subjects repeatedly encountered sentences in which a verb was temporarily ambiguous between main verb (MV) and reduced relative clause (RC) interpretations. They found that subjects who had higher levels of exposure to the unexpected RC interpretation of the sentences had an easier time reading the RC sentences but a more difficult time reading the MV sentences. They concluded that syntactic adaptation occurs rapidly in unexpected structures and also results in difficulty with processing the previously expected alternative structures. This article presents two experiments. Experiment 1 was designed as a follow-up to Fine et al.'s study and failed to find evidence of adaptation. A power analysis of Fine et al.'s raw data revealed that a similar study would need double the items and four times the subjects to reach 95% power. In Experiment 2 we designed a close replication of Fine et al.'s experiment using these sample size guidelines. No evidence of rapid syntactic adaptation was found in this experiment. The failure to find evidence of adaptation in both experiments calls into question the robustness of the effect.}, } @article {pmid29637634, year = {2018}, author = {Wang, Y and Hall, CK}, title = {Seeding and cross-seeding fibrillation of N-terminal prion protein peptides PrP(120-144).}, journal = {Protein science : a publication of the Protein Society}, volume = {27}, number = {7}, pages = {1304-1313}, pmid = {29637634}, issn = {1469-896X}, support = {R01 EB006006/EB/NIBIB NIH HHS/United States ; }, mesh = {Amyloid/*chemistry ; Animals ; Arvicolinae ; Circular Dichroism ; Humans ; Hydrophobic and Hydrophilic Interactions ; Kinetics ; Mesocricetus ; Models, Molecular ; Molecular Dynamics Simulation ; Peptide Fragments/*chemistry ; Prion Proteins/*chemistry ; Protein Structure, Secondary ; }, abstract = {Prion diseases are infectious neurodegenerative diseases that are capable of cross-species transmission, thus arousing public health concerns. Seed-templating propagation of prion protein is believed to underlie prion cross-species transmission pathology. Understanding the molecular fundamentals of prion propagation is key to unravelling the pathology of prion diseases. In this study, we use coarse-grained molecular dynamics to investigate the seeding and cross-seeding aggregation of three prion protein fragments PrP(120-144) originating from human (Hu), bank vole (BV), and Syrian hamster (SHa). We find that the seed accelerates the aggregation of the monomer peptides by eliminating the lag phase. The monomer aggregation kinetics are mainly determined by the structure of the seed. The stronger the hydrophobic residues on the seed associate with each other, the higher the probability that the seed recruits monomer peptides to its surface/interface. For cross-seeding aggregation, we show that Hu has a strong tendency to adopt the conformation of the BV seed and vice versa; the Hu and BV monomers have a weak tendency to adopt the conformation of the SHa seed. These two findings are consistent with Apostol et al.'s experimental findings on PrP(138-143) and partially consistent with Jones et al.'s finding on PrP(23-144). We also identify several conformational mismatches when SHa cross-seeds BV and Hu peptides, indicating the existence of a cross-seeding barrier between SHa and the other two sequences. This study sheds light on the molecular mechanism of seed-templating aggregation of prion protein fragments underlying the sequence-dependent transmission barrier in prion diseases.}, } @article {pmid29629824, year = {2018}, author = {Carlson, MT}, title = {Making Room for Second Language Phonotactics: Effects of L2 Learning and Environment on First Language Speech Perception.}, journal = {Language and speech}, volume = {61}, number = {4}, pages = {598-614}, doi = {10.1177/0023830918767208}, pmid = {29629824}, issn = {1756-6053}, mesh = {Adult ; Female ; Humans ; *Language ; *Learning ; Male ; *Multilingualism ; *Phonetics ; Spain ; *Speech Perception ; United States ; Young Adult ; }, abstract = {Language-specific restrictions on sound sequences in words can lead to automatic perceptual repair of illicit sound sequences. As an example, no Spanish words begin with /s/-consonant sequences ([#sC]), and where necessary (e.g., foreign loanwords) [#sC] is repaired by inserting an initial [e], (e.g. foreign loanwords, cf., esnob, from English snob). As a result, Spanish speakers tend to perceive an illusory [e] before [#sC] sequences. Interestingly, this perceptual illusion is weaker in early Spanish-English bilinguals, whose other language, English, allows [#sC]. The present study explored whether this apparent influence of the English language on Spanish is restricted to early bilinguals, whose early language experience includes a mixture of both languages, or whether later learning of second language (L2) English can also induce a weakening of the first language (L1) perceptual illusion. Two groups of late Spanish-English bilinguals, immersed in Spanish or English, were tested on the same Spanish AX (same-different) discrimination task used in a study by Carlson et al., (2016) and their results compared with the Spanish monolinguals from Carlson et al.'s study. Like early bilinguals, late bilinguals exhibited a reduced impact of perceptual prothesis on discrimination accuracy. Additionally, late bilinguals, particularly in English immersion, were slowest when responding against the Spanish perceptual illusion. Robust L1 perceptual illusions thus appear to be malleable in the face of later L2 learning. It is argued that these results are consonant with the need for late bilinguals to navigate alternative, conflicting representations of the same acoustic material, even in unilingual L1 speech perception tasks.}, } @article {pmid29629398, year = {2017}, author = {Ganesan, P and Shillieto, KE and Ghoraani, B}, title = {Simulation of Spiral Waves and Point Sources in Atrial Fibrillation with Application to Rotor Localization.}, journal = {Proceedings. IEEE International Symposium on Computer-Based Medical Systems}, volume = {2017}, number = {}, pages = {379-384}, pmid = {29629398}, issn = {2372-918X}, support = {R15 HL127663/HL/NHLBI NIH HHS/United States ; }, abstract = {Cardiac simulations play an important role in studies involving understanding and investigating the mechanisms of cardiac arrhythmias. Today, studies of arrhythmogenesis and maintenance are largely being performed by creating simulations of a particular arrhythmia with high accuracy comparable to the results of clinical experiments. Atrial fibrillation (AF), the most common arrhythmia in the United States and many other parts of the world, is one of the major field where simulation and modeling is largely used. AF simulations not only assist in understanding its mechanisms but also help to develop, evaluate and improve the computer algorithms used in electrophysiology (EP) systems for ablation therapies. In this paper, we begin with a brief overeview of some common techniques used in simulations to simulate two major AF mechanisms - spiral waves (or rotors) and point (or focal) sources. We particularly focus on 2D simulations using Nygren et al.'s mathematical model of human atrial cell. Then, we elucidate an application of the developed AF simulation to an algorithm designed for localizing AF rotors for improving current AF ablation therapies. Our simulation methods and results, along with the other discussions presented in this paper is aimed to provide engineers and professionals with a working-knowledge of application-specific simulations of spirals and foci.}, } @article {pmid29621249, year = {2018}, author = {Cogoni, C and Carnaghi, A and Mitrovic, A and Leder, H and Fantoni, C and Silani, G}, title = {Understanding the mechanisms behind the sexualized-body inversion hypothesis: The role of asymmetry and attention biases.}, journal = {PloS one}, volume = {13}, number = {4}, pages = {e0193944}, pmid = {29621249}, issn = {1932-6203}, mesh = {*Attention ; Female ; *Human Body ; Humans ; Male ; *Models, Psychological ; Photic Stimulation ; Sexual Behavior/*psychology ; Young Adult ; }, abstract = {A controversial hypothesis, named the Sexualized Body Inversion Hypothesis (SBIH), claims similar visual processing of sexually objectified women (i.e., with a focus on the sexual body parts) and inanimate objects as indicated by an absence of the inversion effect for both type of stimuli. The current study aims at shedding light into the mechanisms behind the SBIH in a series of 4 experiments. Using a modified version of Bernard et al.´s (2012) visual-matching task, first we tested the core assumption of the SBIH, namely that a similar processing style occurs for sexualized human bodies and objects. In Experiments 1 and 2 a non-sexualized (personalized) condition plus two object-control conditions (mannequins, and houses) were included in the experimental design. Results showed an inversion effect for images of personalized women and mannequins, but not for sexualized women and houses. Second, we explored whether this effect was driven by differences in stimulus asymmetry, by testing the mediating and moderating role of this visual feature. In Experiment 3, we provided the first evidence that not only the sexual attributes of the images but also additional perceptual features of the stimuli, such as their asymmetry, played a moderating role in shaping the inversion effect. Lastly, we investigated the strategy adopted in the visual-matching task by tracking eye movements of the participants. Results of Experiment 4 suggest an association between a specific pattern of visual exploration of the images and the presence of the inversion effect. Findings are discussed with respect to the literature on sexual objectification.}, } @article {pmid29609680, year = {2018}, author = {Twis, MK and Nguyen, AP and Nordberg, A}, title = {Intimate Partner Violence Myths in Police Reports: A Directed Content Analysis.}, journal = {Violence and victims}, volume = {33}, number = {2}, pages = {351-367}, doi = {10.1891/0886-6708.VV-D-17-00015}, pmid = {29609680}, issn = {0886-6708}, mesh = {*Attitude ; Coercion ; Crime Victims ; Criminals ; Decision Making ; Female ; Gender Identity ; Humans ; *Intimate Partner Violence ; Law Enforcement ; Male ; Mythology ; *Police ; *Prejudice ; Social Norms ; Social Stigma ; }, abstract = {Although much has changed in social and criminal justice system responses to intimate partner violence (IPV) since public awareness campaigns began in the 1970s, stigmatization around IPV offense and victimization remains a barrier to victims obtaining available assistance, including those offered by police forces. Unfortunately, stigma is often perpetuated by mythology about the crime, its offenders, its victims, and overarching gender norms. Since IPV cases are managed under the auspices of the criminal justice system, the manner in which the system itself perpetuates IPV myths is worthy of attention. Prior literature suggests that police officers may be vulnerable to this mythology in their decision-making and reporting of IPV calls. This is troubling for IPV victims and offenders alike, since police reports follow them through the criminal justice system and associated IPV intervention programs. A report heavily influenced by IPV mythology is unlikely to serve IPV offenders or victims particularly well. Guided by four popular IPV myths identified in Eigenberg et al.'s (2012) study, the purpose of the present qualitative study of IPV in police reports (N = 58) is to explore the influence of IPV mythology on police officers' decision-making and intervention. One overarching theme emerged after the analysis: undetected coercive control evident in the cases. Implications on improvement in police training are suggested.}, } @article {pmid29603115, year = {2018}, author = {Hu, S and Guasti, MT and Gavarró, A}, title = {Chinese Children's Knowledge of Topicalization: Experimental Evidence from a Comprehension Study.}, journal = {Journal of psycholinguistic research}, volume = {47}, number = {6}, pages = {1279-1300}, pmid = {29603115}, issn = {1573-6555}, support = {FFI2014-56968-C4-1-P//the Ministerio de Economía y Competitividad de España/ ; }, mesh = {Child ; Child, Preschool ; China ; *Comprehension ; Female ; Humans ; *Language ; *Language Development ; *Linguistics ; Male ; Psycholinguistics ; }, abstract = {There is a debate as to whether topic structures in Chinese involve A'-movement or result from base-generation of the topic in the left periphery. If Chinese topicalization was derived by movement, under the assumptions of Friedmann et al.'s Relativized Minimality (Lingua 119:67-88, 2009), we would expect children's comprehension of object topicalization (with OSV order) to be worse than their comprehension of subject topicalization (with SVO order). This study examined 146 Mandarin-speaking children from age three to age six by means of a picture-sentence matching task with an appropriate context. The results showed a subject/object asymmetry when the topic marker is overt, and no asymmetry when the topic marker is covert. This suggests that the presence or absence of topic markers play an important role in children's comprehension of topicalization. We propose that both structures involve movement in the adult grammar, but not in the child grammar, at least initially. Sentences without overt topic markers are base-generated on a par with gapless sentences with a topic, and the base-generation analysis is abandoned as soon as children learn the syntax and semantics of topic markers, which function as attractors of topics.}, } @article {pmid29599179, year = {2018}, author = {Rogers, WA and Mintzker, Y}, title = {Response to Brodersen et al' s 'Overdiagnosis: what it is and what it isn't'.}, journal = {BMJ evidence-based medicine}, volume = {23}, number = {3}, pages = {119}, doi = {10.1136/bmjebm-2018-110948}, pmid = {29599179}, issn = {2515-4478}, mesh = {Humans ; *Medical Overuse ; }, } @article {pmid29595443, year = {2017}, author = {Estabrooks, CA}, title = {Engagement-Capable Environments - No Less Challenging than other Large System Changes.}, journal = {HealthcarePapers}, volume = {17}, number = {2}, pages = {40-45}, doi = {10.12927/hcpap.2017.25411}, pmid = {29595443}, issn = {1929-6339}, mesh = {Caregivers ; *Diffusion of Innovation ; Humans ; *Organizational Innovation ; Patient Care Team/*organization & administration ; Patient-Centered Care ; }, abstract = {Kuluski et al.'s (2017) argument for including a more advanced form of health system performance management centred on "the experience of care," raises the major challenge of creating and sustaining engagement-capable environments. Here I briefly address frameworks that may be useful in meeting this challenge - Complex Adaptive Systems, Innovation Diffusion, Whole System Change. I also offer a personal perspective drawn from a successful citizen engagement experience, concluding with a perspective on the numerous challenges we have or are in the process of overcoming compared to the challenges of engagement-capable environments.}, } @article {pmid29595441, year = {2017}, author = {Glasby, J}, title = {Health System Performance Measurement: A UK Perspective.}, journal = {HealthcarePapers}, volume = {17}, number = {2}, pages = {30-33}, doi = {10.12927/hcpap.2017.25413}, pmid = {29595441}, issn = {1929-6339}, mesh = {Delivery of Health Care/*organization & administration ; Humans ; Patient Satisfaction ; Patient-Centered Care ; Quality Indicators, Health Care/*standards/*trends ; *Social Work ; United Kingdom ; }, abstract = {In response to the lead article by Kuluski et al. (2017), this commentary draws on UK debates around the quality of healthcare and on the author's personal experience training as a social worker. Judging whether a service has "worked" has to involve understanding what a good outcome would be for the person receiving it. While carers provide important insights here, the "user" may have a different view, and reconciling different perspectives can be challenging. Although individual services may have fulfilled their part of the process, it is important to look at the person's overall experience (although this is difficult to achieve in practice). There is also no point measuring patient experience if we are not prepared to really listen to the feedback we receive. Moving forward, the UK's personalization agenda - which focuses on giving people greater choice and control - may enhance the aims of Kuluski et al.'s work.}, } @article {pmid29574735, year = {2018}, author = {Sonuga-Barke, EJS and Fearon, P}, title = {Commentary: Whither the epigenetics of child psychopathology? Some reflections provoked by Barker et al. (2018).}, journal = {Journal of child psychology and psychiatry, and allied disciplines}, volume = {59}, number = {4}, pages = {323-326}, doi = {10.1111/jcpp.12906}, pmid = {29574735}, issn = {1469-7610}, mesh = {Adolescent ; Child ; *DNA Methylation ; Epigenesis, Genetic ; Epigenomics ; Humans ; *Mental Disorders ; Psychopathology ; }, abstract = {Barker et al.'s. () review addresses one of the most fundamental questions in the fields of child psychology and psychiatry - How can adverse experiences shape development to a sufficient degree and in profound and enduring ways to create long term risk for later mental disorder and disability? In particular they discuss the plausibility of differential methylation as an epigenetic mechanism by which such exposures can become neuro-biologically embedded. Our commentary rises six question relating to key issues that need to be addressed as we search for definitive evidence from human studies that such mechanisms actually do make an important causal contribution to abnormal trajectories of development to disorder.}, } @article {pmid29572165, year = {2018}, author = {Jeunet, C and Lotte, F and Batail, JM and Philip, P and Micoulaud Franchi, JA}, title = {Using Recent BCI Literature to Deepen our Understanding of Clinical Neurofeedback: A Short Review.}, journal = {Neuroscience}, volume = {378}, number = {}, pages = {225-233}, doi = {10.1016/j.neuroscience.2018.03.013}, pmid = {29572165}, issn = {1873-7544}, mesh = {*Brain-Computer Interfaces ; Humans ; Mental Disorders/rehabilitation ; *Neurofeedback ; }, abstract = {In their recent paper, Alkoby et al. (2017) provide the readership with an extensive and very insightful review of the factors influencing NeuroFeedback (NF) performance. These factors are drawn from both the NF literature and the Brain-Computer Interface (BCI) literature. Our short review aims to complement Alkoby et al.'s review by reporting recent additions to the BCI literature. The object of this paper is to highlight this literature and discuss its potential relevance and usefulness to better understand the processes underlying NF and further improve the design of clinical trials assessing NF efficacy. Indeed, we are convinced that while NF and BCI are fundamentally different in many ways, both the BCI and NF communities could reach compelling achievements by building upon one another. By reviewing the recent BCI literature, we identified three types of factors that influence BCI performance: task-specific, cognitive/motivational and technology-acceptance-related factors. Since BCIs and NF share a common goal (i.e., learning to modulate specific neurophysiological patterns), similar cognitive and neurophysiological processes are likely to be involved during the training process. Thus, the literature on BCI training may help (1) to deepen our understanding of neurofeedback training processes and (2) to understand the variables that influence the clinical efficacy of NF. This may help to properly assess and/or control the influence of these variables during randomized controlled trials.}, } @article {pmid29559907, year = {2018}, author = {Alber, J and McGarry, K and Noto, RB and Snyder, PJ}, title = {Use of Eflornithine (DFMO) in the Treatment of Early Alzheimer's Disease: A Compassionate Use, Single-Case Study.}, journal = {Frontiers in aging neuroscience}, volume = {10}, number = {}, pages = {60}, pmid = {29559907}, issn = {1663-4365}, abstract = {Background: Recent genome-wide association screening (GWAS) studies have linked Alzheimer's disease (AD) neuropathology to gene networks that regulate immune function. Kan et al. recently reported that Arg1 (an anti-inflammatory gene that codes for arginase-1) is expressed in parts of the brain associated with amyloidosis prior to the onset of neuronal loss, suggesting that chronic brain arginine deprivation promotes AD-related neuropathology. They blocked arginine catabolism in their mouse AD model by administration of eflornithine (DFMO) to juvenile animals, effectively blocking the expression of AD-related amyloid pathology as the mice aged. We report results from a single-case study in which DFMO was administered, for the first time, in an attempt to slow progression of AD in a single woman with multi-domain, amnestic MCI who was unable to tolerate an acetylcholinesterase inhibitor. Methods: Patient C.S. is a 74-year old female with a 5-year history of cognitive decline who was placed on DFMO (500 mg b.i.d.) for 12 months, with amyloid PET scans (baseline and 12-months), APOE genotyping and neuropsychological exams at baseline, 3, 9, and 12 months. Results: C.S. suffered continued cognitive decline over 12 months, including progressive worsening of orientation, social functions and ability to engage in IADL's. She also showed progressive decline on measures of episodic memory and executive function. Florbetapir PET imaging yielded elevated total neocortical SUVr scores at both baseline (SUVr = 1.55) and at 12 months (SUVr = 1.69). Conclusions: We report a first attempt at using DFMO to slow AD progression. This 12-month single-case trial did not halt continued amyloidosis nor cognitive decline. Although this trial was predicated on data reported by Kan et al. (2015) showing that DFMO administered to juvenile AD-prone mice led to diminished amyloid aggregation, this attempt to treat an older mild AD patient may not be a fair test of Kan et al.'s model and results. A future trial might seek to block amyloidosis in young adults who are autosomal gene carriers for early onset AD, or perhaps in adults who are very clearly in the pre-clinical disease stage. Trial Registration: This trial was registered as a Compassionate Use IND #128888 with the United States Food and Drug Administration (FDA).}, } @article {pmid29553787, year = {2018}, author = {King, PR and Beehler, GP and Vest, BM and Donnelly, K and Wray, LO}, title = {Qualitative exploration of traumatic brain injury-related beliefs among U.S. military veterans.}, journal = {Rehabilitation psychology}, volume = {63}, number = {1}, pages = {121-130}, doi = {10.1037/rep0000165}, pmid = {29553787}, issn = {1939-1544}, support = {//VA Center for Integrated Health Care/International ; //Department of Veterans Affairs; Office of Academic Affiliations; Advanced Fellowship Program in Mental Illness Research/International ; }, mesh = {Brain Injuries, Traumatic/*psychology ; Evaluation Studies as Topic ; Female ; *Health Knowledge, Attitudes, Practice ; Humans ; Interview, Psychological ; Male ; Middle Aged ; Neuropsychological Tests ; United States ; Veterans/*psychology ; }, abstract = {PURPOSE/OBJECTIVE: Explore cognitive, affective, and experiential factors that inform veterans' traumatic brain injury (TBI)-related beliefs. Research Method/Design: Qualitative descriptive study of 22 veterans who received care for TBI at a VA Medical Center in the Northeastern United States using directed content analysis. Measures included a semistructured interview, demographic survey, the Alcohol Use Disorders Identification Test-Consumption Items (AUDIT-C), Patient Health Questionnaire-9 (PHQ-9), PTSD Checklist (PCL), Neurobehavioral Symptom Inventory (NSI), and Insomnia Severity Index (ISI).

RESULTS: Results were organized according to Leventhal et al.'s (1997) illness perception model, including veterans' self-reports regarding: (a) knowledge of TBI, labels, and symptoms (identity); (b) etiology (cause); (c) the biopsychosocial impact of TBI (consequences); (d) symptom chronicity (timeline); and (e) recovery expectancy and management strategies (controllability). Participants identified common causes of TBI, as well as acute symptoms. Uncertainty was present with regard to TBI nomenclature, recovery expectancies and trajectories, and the impact of co-occurring mental health diagnoses.

CONCLUSIONS/IMPLICATIONS: Opportunity exists to improve TBI-related education in the course of routine, patient-centered care. Clinicians should take into account the subjective beliefs and experiences, including co-occurring mental health conditions, that inform patients' illness representations to improve patient-provider communication and the quality of TBI care. (PsycINFO Database Record}, } @article {pmid29551987, year = {2018}, author = {Chen, YH and Lin, YJ}, title = {Validation of the Short Self-Regulation Questionnaire for Taiwanese College Students (TSSRQ).}, journal = {Frontiers in psychology}, volume = {9}, number = {}, pages = {259}, pmid = {29551987}, issn = {1664-1078}, abstract = {While self-regulation has long been recognized as an important characteristic of an individual, instruments assessing the general aptitude of self-regulation remain limited especially in Asian countries. This study re-validated Carey et al.'s (2004) Short Self-Regulation Questionnaire based on a national sample of Taiwanese college students (N = 1,988). Item analysis, exploratory factor analysis, and confirmatory factor analysis (CFA) yielded 22 items in five internally consistent factors. Descriptive findings showed that, a lack of proactiveness and volitional control, and a decrease of self-regulation throughout the college span appeared to be an overarching problem among Taiwanese college students. Furthermore, male students achieved lower self-regulation scores than female ones, and students in Services and STEM-related majors are in the need of self-regulation enhancement. Due to the generic measurement of individual's self-regulation traits, the Taiwanese Short Self-regulation Questionnaire (TSSRQ) can be flexibly applied to various contexts and used to deal with different issues beyond learning such as college students' Internet or smartphone addiction. Through this study, we hope the validated TSSRQ can promote studies on self-regulation and associated antecedents and outcomes, in turn leveraging college students' life adjustment and well-being.}, } @article {pmid29547619, year = {2018}, author = {Qiu, S and Xu, G and Ahmad, H and Guo, Y}, title = {An enhanced password authentication scheme for session initiation protocol with perfect forward secrecy.}, journal = {PloS one}, volume = {13}, number = {3}, pages = {e0194072}, pmid = {29547619}, issn = {1932-6203}, mesh = {Communication ; *Computer Security ; *Confidentiality ; Health Smart Cards/*methods ; Information Systems ; Internet ; Multimedia ; Social Responsibility ; Software ; }, abstract = {The Session Initiation Protocol (SIP) is an extensive and esteemed communication protocol employed to regulate signaling as well as for controlling multimedia communication sessions. Recently, Kumari et al. proposed an improved smart card based authentication scheme for SIP based on Farash's scheme. Farash claimed that his protocol is resistant against various known attacks. But, we observe some accountable flaws in Farash's protocol. We point out that Farash's protocol is prone to key-compromise impersonation attack and is unable to provide pre-verification in the smart card, efficient password change and perfect forward secrecy. To overcome these limitations, in this paper we present an enhanced authentication mechanism based on Kumari et al.'s scheme. We prove that the proposed protocol not only overcomes the issues in Farash's scheme, but it can also resist against all known attacks. We also provide the security analysis of the proposed scheme with the help of widespread AVISPA (Automated Validation of Internet Security Protocols and Applications) software. At last, comparing with the earlier proposals in terms of security and efficiency, we conclude that the proposed protocol is efficient and more secure.}, } @article {pmid29535997, year = {2018}, author = {Fertleman, C and Aubugeau-Williams, P and Sher, C and Lim, AN and Lumley, S and Delacroix, S and Pan, X}, title = {A Discussion of Virtual Reality As a New Tool for Training Healthcare Professionals.}, journal = {Frontiers in public health}, volume = {6}, number = {}, pages = {44}, pmid = {29535997}, issn = {2296-2565}, abstract = {BACKGROUND: Virtual reality technology is an exciting and emerging field with vast applications. Our study sets out the viewpoint that virtual reality software could be a new focus of direction in the development of training tools in medical education. We carried out a panel discussion at the Center for Behavior Change 3rd Annual Conference, prompted by the study, "The Responses of Medical General Practitioners to Unreasonable Patient Demand for Antibiotics--A Study of Medical Ethics Using Immersive Virtual Reality" (1).

METHODS: In Pan et al.'s study, 21 general practitioners (GPs) and GP trainees took part in a videoed, 15-min virtual reality scenario involving unnecessary patient demands for antibiotics. This paper was discussed in-depth at the Center for Behavior Change 3rd Annual Conference; the content of this paper is a culmination of findings and feedback from the panel discussion. The experts involved have backgrounds in virtual reality, general practice, medicines management, medical education and training, ethics, and philosophy.

VIEWPOINT: Virtual reality is an unexplored methodology to instigate positive behavioral change among clinicians where other methods have been unsuccessful, such as antimicrobial stewardship. There are several arguments in favor of use of virtual reality in medical education: it can be used for "difficult to simulate" scenarios and to standardize a scenario, for example, for use in exams. However, there are limitations to its usefulness because of the cost implications and the lack of evidence that it results in demonstrable behavior change.}, } @article {pmid29533359, year = {2019}, author = {Maciejewski, H and Rahmani, A and Chorin, F and Lardy, J and Samozino, P and Ratel, S}, title = {Methodological Considerations on the Relationship Between the 1,500-m Rowing Ergometer Performance and Vertical Jump in National-Level Adolescent Rowers.}, journal = {Journal of strength and conditioning research}, volume = {33}, number = {11}, pages = {3000-3007}, doi = {10.1519/JSC.0000000000002406}, pmid = {29533359}, issn = {1533-4287}, mesh = {Adolescent ; *Athletic Performance ; Body Mass Index ; *Ergometry ; Exercise Test/*methods ; Humans ; Male ; *Water Sports ; }, abstract = {Maciejewski, H, Rahmani, A, Chorin, F, Lardy, J, Samozino, P, and Ratel, S. Methodological considerations on the relationship between the 1,500-m rowing ergometer performance and vertical jump in national-level adolescent rowers. J Strength Cond Res 33(11): 3000-3007, 2019-The purpose of this study was to investigate whether 3 different approaches for evaluating squat jump performance were correlated with rowing ergometer performance in elite adolescent rowers. Fourteen young male competitive rowers (15.3 ± 0.6 years), who took part in the French rowing national championships, performed a 1,500-m all-out rowing ergometer performance (P1500) and a squat jump (SJ) test. The performance in SJ was determined by calculating the jump height (HSJ in cm), a jump index (ISJ = HSJ·body mass·gravity, in J), and the mean power output (PSJ in W) from the Samozino et al.'s method. Furthermore, allometric modeling procedures were used to consider the importance of body mass (BM) in the relationships between P1500 and jump scores. P1500 was significantly correlated with HSJ (r = 0.29, p ≤ 0.05), ISJ (r = 0.72, p < 0.0001), and PSJ (r = 0.86, p < 0.0001). Furthermore, BM explained at least 96% of the relationships between SJ and rowing performances. However, the similarity between both allometric exponents for PSJ and P1500 (1.15 and 1.04, respectively) indicates that BM could influence jump and rowing ergometer performances at the same rate, and that PSJ could be the best correlate of P1500. Therefore, the calculation of power seems to be more relevant than HSJ and ISJ to (a) evaluate jump performance and (b) infer the capacity of adolescent rowers to perform 1,500-m all-out rowing ergometer performance, irrespective of their body mass. This could help coaches to improve their training program and potentially identify talented young rowers.}, } @article {pmid29525555, year = {2018}, author = {Santangelo, G and Garramone, F and Baiano, C and D'Iorio, A and Raimo, S and Vitale, C}, title = {Reply to Zappia et al.'s comment on personality and Parkinson's Disease: A meta-analysis.}, journal = {Parkinsonism & related disorders}, volume = {51}, number = {}, pages = {116}, doi = {10.1016/j.parkreldis.2018.02.041}, pmid = {29525555}, issn = {1873-5126}, mesh = {Humans ; *Parkinson Disease ; Personality ; Personality Disorders ; }, } @article {pmid29525131, year = {2018}, author = {Lees, KE and Guthrie, BJ and Henderson, EL and Jimison, HB and Sceppa, C and Pavel, M and Gordon, C and Fulmer, T}, title = {NUCare: Advancing research on technological integration for self-management in the aging population.}, journal = {Nursing outlook}, volume = {66}, number = {2}, pages = {121-129}, pmid = {29525131}, issn = {1528-3968}, support = {P20 NR015320/NR/NINR NIH HHS/United States ; }, mesh = {Advisory Committees ; *Aging ; Faculty, Nursing ; Humans ; National Institute of Nursing Research (U.S.) ; Nursing Research/*organization & administration ; Pilot Projects ; Population Dynamics ; Program Development ; Program Evaluation ; *Self-Management ; Surveys and Questionnaires ; United States ; }, abstract = {BACKGROUND: The Center for Technology in Support of Self-Management and Health (NUCare) is an exploratory research center funded by the National Institute of Nursing Research's P20 mechanism positioned to conduct rigorous research on the integration of technology in the self-management of the older adult population.

PURPOSE: The purpose of this paper is to describe the development and application of an evaluation plan and preliminary evaluation results from the first year of implementation.

METHODS: This evaluation plan is derived from and is consistent with Dorsey et al.'s (2014) logic model. Dorsey's model provided guidelines for evaluating sustainability, leveraging of resources, and interdisciplinary collaboration within the center.

DISCUSSION: Preliminary results and strategies for addressing findings from the first year of evaluation are discussed. A secondary aim of this paper is to showcase the relevance of this center to the advancement and maintenance of health in the aging population.}, } @article {pmid29517257, year = {2018}, author = {Masapollo, M and Polka, L and Ménard, L and Franklin, L and Tiede, M and Morgan, J}, title = {Asymmetries in unimodal visual vowel perception: The roles of oral-facial kinematics, orientation, and configuration.}, journal = {Journal of experimental psychology. Human perception and performance}, volume = {44}, number = {7}, pages = {1103-1118}, pmid = {29517257}, issn = {1939-1277}, support = {R01 HD068501/HD/NICHD NIH HHS/United States ; //Natural Sciences and Engineering Research Council/ ; //National Institutes of Health/ ; }, mesh = {Adult ; Eye Movement Measurements ; Female ; Humans ; Male ; Mouth/*physiology ; Psycholinguistics ; Speech/*physiology ; Speech Perception/*physiology ; Visual Perception/*physiology ; Young Adult ; }, abstract = {Masapollo, Polka, and Ménard (2017) recently reported a robust directional asymmetry in unimodal visual vowel perception: Adult perceivers discriminate a change from an English /u/ viseme to a French /u/ viseme significantly better than a change in the reverse direction. This asymmetry replicates a frequent pattern found in unimodal auditory vowel perception that points to a universal bias favoring more extreme vocalic articulations, which lead to acoustic signals with increased formant convergence. In the present article, the authors report 5 experiments designed to investigate whether this asymmetry in the visual realm reflects a speech-specific or general processing bias. They successfully replicated the directional effect using Masapollo et al.'s dynamically articulating faces but failed to replicate the effect when the faces were shown under static conditions. Asymmetries also emerged during discrimination of canonically oriented point-light stimuli that retained the kinematics and configuration of the articulating mouth. In contrast, no asymmetries emerged during discrimination of rotated point-light stimuli or Lissajou patterns that retained the kinematics, but not the canonical orientation or spatial configuration, of the labial gestures. These findings suggest that the perceptual processes underlying asymmetries in unimodal visual vowel discrimination are sensitive to speech-specific motion and configural properties and raise foundational questions concerning the role of specialized and general processes in vowel perception. (PsycINFO Database Record}, } @article {pmid29496751, year = {2018}, author = {Dheensa, S and Samuel, G and Lucassen, AM and Farsides, B}, title = {Towards a national genomics medicine service: the challenges facing clinical-research hybrid practices and the case of the 100 000 genomes project.}, journal = {Journal of medical ethics}, volume = {44}, number = {6}, pages = {397-403}, pmid = {29496751}, issn = {1473-4257}, support = {//Wellcome Trust/United Kingdom ; }, mesh = {Clinical Protocols ; Community Participation ; Evidence-Based Medicine ; Genetic Predisposition to Disease ; Genetics, Medical/*ethics ; Genome, Human/*genetics ; Health Knowledge, Attitudes, Practice ; Humans ; Informed Consent/*ethics ; Moral Obligations ; Professional-Patient Relations/*ethics ; Rare Diseases/*genetics ; Whole Genome Sequencing ; }, abstract = {Clinical practice and research are governed by distinct rules and regulations and have different approaches to, for example, consent and providing results. However, genomics is an example of where research and clinical practice have become codependent. The 100 000 genomes project (100kGP) is a hybrid venture where a person can obtain a clinical investigation only if he or she agrees to also participate in ongoing research-including research by industry and commercial companies. In this paper, which draws on 20 interviews with professional stakeholders involved in 100kGP, we investigate the ethical issues raised by this project's hybrid nature. While some interviewees thought the hybrid nature of 100kGP was its vanguard, interviewees identified several tensions around hybrid practice: how to decide who should be able to participate; how to determine whether offering results might unduly influence participation into wide-ranging but often as yet unknown research and how to ensure that patients/families do not develop false expectations about receiving results. These areas require further debate as 100kGP moves into routine healthcare in the form of the national genomic medicine service. To address the tensions identified, we explore the appropriateness of Faden et al.'s framework of ethical obligations for when research and clinical care are completely integrated. We also argue that enabling ongoing transparent and trustworthy communication between patients/families and professionals around the kinds of research that should be permitted in 100kGP will help to understand and ensure that expectations remain realistic. Our paper aims to encourage a focused discussion about these issues and to inform a new 'social contract' for research and clinical care in the health service.}, } @article {pmid29496210, year = {2018}, author = {Moore, J and Koon, HEC}, title = {Response to González et al.'s comment upon "Basilar portion porosity: A pathological lesion possibly associated with infantile scurvy".}, journal = {International journal of paleopathology}, volume = {20}, number = {}, pages = {116}, doi = {10.1016/j.ijpp.2017.09.004}, pmid = {29496210}, issn = {1879-9825}, mesh = {*Ascorbic Acid Deficiency ; Humans ; Porosity ; *Scurvy ; }, } @article {pmid29489619, year = {2018}, author = {Shirai, K and Takata, M and Takahara, A and Shimizu, K}, title = {Medical science is based on evidence (answer to Spronck et al.'s refutation: physics cannot be disputed).}, journal = {Journal of hypertension}, volume = {36}, number = {4}, pages = {958-960}, doi = {10.1097/HJH.0000000000001661}, pmid = {29489619}, issn = {1473-5598}, mesh = {Ankle ; Blood Pressure ; Blood Pressure Determination ; Physics ; *Vascular Stiffness ; }, } @article {pmid29486707, year = {2018}, author = {Gasser, S and Reichenspurner, H and Girdauskas, E}, title = {Genomic analysis in patients with myxomatous mitral valve prolapse: current state of knowledge.}, journal = {BMC cardiovascular disorders}, volume = {18}, number = {1}, pages = {41}, pmid = {29486707}, issn = {1471-2261}, mesh = {Adult ; Echocardiography ; Female ; Genetic Markers ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Heredity ; Humans ; Male ; Middle Aged ; Mitral Valve/*abnormalities/diagnostic imaging/physiopathology ; Mitral Valve Prolapse/diagnostic imaging/*genetics/physiopathology ; Pedigree ; Prognosis ; Risk Factors ; }, abstract = {BACKGROUND: Myxomatous mitral valve prolapse is a common cardiac abnormality. Morbus Barlow is characterized by excess myxomatous leaflet tissue, bileaflet prolapse or billowing, chordae elongation and annular dilatation with or without calcification. Extensive myxoid degeneration with destruction of the normal three-layered leaflet tissue architecture is observed histologically in such patients. Autosomal dominant inheritance with an age and sex-dependent expression has long been recognised. This review explores the current understanding of the genetics of bileaflet prolapse, with a focus on genetic analysis and the role for echocardiographical screening of the first degree relatives of affected patients.

METHODS: Systematic literature searches were performed using PubMed and Embase up to September 2017. In Disse et al.'s study (study one) first degree relatives of 25 patients with Morbus Barlow who underwent mitral valve repair were screened for bileaflet valve prolapse. In Nesta et al.'s study one family with three living generations of 43 individuals with 9 confirmed cases of MVP was screened. Genotyping was performed in four families for 344 microsatellite markers from Chromosome 1 to 16.

RESULTS: In study one, autosomal dominant inheritance was shown in four pedigrees. Genome-wide linkage analysis of the most informative pedigree (24 individuals, three generations) showed a significant linkage for markers mapping to chromosome 16p. Linkage to this locus was confirmed in a second family within the same study, but was excluded in the remaining two pedigrees. In study two an autosomal dominant locus was mapped to chromosome 13. 8 of the 9 individuals affected were found to suffer from bileaflet prolapse.

CONCLUSIONS: Barlow's disease is a heritable trait but the genetic causes remain largely elusive. Ch16p11.2-p12.1 is the only locus proven to be associated with bileaflet prolapse. Locus 13.q31.3-q32.1 was shown to cause bileaflet as well as posterior leaflet prolapse. This review intends to make physicians aware of genetic causes of myxomatous mitral valve prolapse, thereby emphasising the importance of cardiological examination of first-degree relatives of patients with Morbus Barlow. Integrated and more comprehensive studies are needed for identification of genes involved in this heterogenic disease. Further genomic studies may facilitate more individualised and accurate risk assessment and may help to develop possible preventive stategies for patients in the future.}, } @article {pmid29481615, year = {2018}, author = {McAuliffe, WE}, title = {Critique of Cheatle et al.'s Study of Risk of Opioid Use Disorder Due to Prescribing Opioids for Chronic Noncancer Pain.}, journal = {Pain medicine (Malden, Mass.)}, volume = {19}, number = {5}, pages = {1100-1101}, doi = {10.1093/pm/pnx313}, pmid = {29481615}, issn = {1526-4637}, mesh = {Analgesics, Opioid ; *Chronic Pain ; Humans ; *Opioid-Related Disorders ; Primary Health Care ; }, } @article {pmid29477428, year = {2018}, author = {Li, CT and Shih, DH and Wang, CC}, title = {Cloud-assisted mutual authentication and privacy preservation protocol for telecare medical information systems.}, journal = {Computer methods and programs in biomedicine}, volume = {157}, number = {}, pages = {191-203}, doi = {10.1016/j.cmpb.2018.02.002}, pmid = {29477428}, issn = {1872-7565}, mesh = {*Cloud Computing ; Computer Security/*standards ; *Confidentiality ; Delivery of Health Care/organization & administration ; Humans ; *Information Systems ; Telemedicine/*organization & administration ; }, abstract = {BACKGROUND AND OBJECTIVE: With the rapid development of wireless communication technologies and the growing prevalence of smart devices, telecare medical information system (TMIS) allows patients to receive medical treatments from the doctors via Internet technology without visiting hospitals in person. By adopting mobile device, cloud-assisted platform and wireless body area network, the patients can collect their physiological conditions and upload them to medical cloud via their mobile devices, enabling caregivers or doctors to provide patients with appropriate treatments at anytime and anywhere. In order to protect the medical privacy of the patient and guarantee reliability of the system, before accessing the TMIS, all system participants must be authenticated.

METHODS:  Mohit et al. recently suggested a lightweight authentication protocol for cloud-based health care system. They claimed their protocol ensures resilience of all well-known security attacks and has several important features such as mutual authentication and patient anonymity. In this paper, we demonstrate that Mohit et al.'s authentication protocol has various security flaws and we further introduce an enhanced version of their protocol for cloud-assisted TMIS, which can ensure patient anonymity and patient unlinkability and prevent the security threats of report revelation and report forgery attacks.

RESULTS:  The security analysis proves that our enhanced protocol is secure against various known attacks as well as found in Mohit et al.'s protocol. Compared with existing related protocols, our enhanced protocol keeps the merits of all desirable security requirements and also maintains the efficiency in terms of computation costs for cloud-assisted TMIS.

CONCLUSIONS:  We propose a more secure mutual authentication and privacy preservation protocol for cloud-assisted TMIS, which fixes the mentioned security weaknesses found in Mohit et al.'s protocol. According to our analysis, our authentication protocol satisfies most functionality features for privacy preservation and effectively cope with cloud-assisted TMIS with better efficiency.}, } @article {pmid29468692, year = {2018}, author = {Hoff, E and Core, C}, title = {ADVANCES IN THE ASSESSMENT OF YOUNG BILINGUALS: COMMENTS ON FLOCCIA ET AL.}, journal = {Monographs of the Society for Research in Child Development}, volume = {83}, number = {1}, pages = {109-123}, pmid = {29468692}, issn = {1540-5834}, support = {R01 HD068421/HD/NICHD NIH HHS/United States ; }, mesh = {Child, Preschool ; Humans ; *Language Development ; *Learning ; *Multilingualism ; Research ; }, abstract = {In this article, we comment on the significant contributions to science and to clinical practice made by Floccia et al.'s study of over 400 bilingual 2-year-old children. To science, this work contributes new findings on the linguistic factors that make some pairs of languages easier to learn than others and rich data on the environmental factors that influence bilingual development. Their results provide clues to the nature of the language learning process. To clinical practice, Floccia et al. contribute a new instrument for the diagnosis of risk for language impairment in bilingual children and a new method for the development of assessment instruments more generally. The experience-adjusted approach to norming that they illustrate here provides an example for others to follow. Their method holds promise for test development in many domains where the goal is to assess children's internal capacity but the evidence that is available in children's achievement is systematically influenced by environmental factors.}, } @article {pmid29467164, year = {2018}, author = {Pugh, EN}, title = {The discovery of the ability of rod photoreceptors to signal single photons.}, journal = {The Journal of general physiology}, volume = {150}, number = {3}, pages = {383-388}, pmid = {29467164}, issn = {1540-7748}, mesh = {Animals ; Humans ; *Photons ; Retinal Rod Photoreceptor Cells/metabolism/*physiology ; Sensory Thresholds ; *Vision, Ocular ; }, abstract = {Vertebrate rod photoreceptors evolved the astonishing ability to respond reliably to single photons. In parallel, the proximate neurons of the visual system evolved the ability to reliably encode information from a few single-photon responses (SPRs) as arising from the presence of an object of interest in the visual environment. These amazing capabilities were first inferred from measurements of human visual threshold by Hecht et al. (1942), whose paper has since been cited over 1,000 times. Subsequent research, in part inspired by Hecht et al.'s discovery, has directly measured rod SPRs, characterized the molecular mechanism responsible for their generation, and uncovered much about the specializations in the retina that enable the reliable transmission of SPRs in the teeth of intrinsic neuronal noise.}, } @article {pmid29457556, year = {2017}, author = {Berent, I}, title = {Is markedness a confused concept?.}, journal = {Cognitive neuropsychology}, volume = {34}, number = {7-8}, pages = {493-499}, doi = {10.1080/02643294.2017.1422485}, pmid = {29457556}, issn = {1464-0627}, mesh = {Female ; Humans ; Linguistics/*methods ; Male ; }, abstract = {It is well known that, across languages, certain phonological features are more frequent than others. But whether these facts reflect abstract universal markedness constraints or functional pressures (auditory and articulatory difficulties and lexical frequency) is unknown. Romani, Galuzzi, Guariglia, and Goslin (2017) report that the putative markedness of phonological features captures their order of acquisition and their propensity to elicit errors in patients with an apraxia of speech (but not in phonological aphasia). The authors believe these results challenge the existence of abstract markedness constraints. They also raise some concerns about the explanatory utility of the markedness hypothesis. This commentary demonstrates that markedness is not inherently vague or vacuous nor is it falsified by Romani et al.'s empirical findings. As such, these results leave wide open the possibility that some phonological markedness constraints are abstract.}, } @article {pmid29453697, year = {2018}, author = {Horn, JP}, title = {The sacral autonomic outflow is parasympathetic: Langley got it right.}, journal = {Clinical autonomic research : official journal of the Clinical Autonomic Research Society}, volume = {28}, number = {2}, pages = {181-185}, pmid = {29453697}, issn = {1619-1560}, mesh = {Animals ; Autonomic Nervous System/*physiology ; Humans ; Neurons/physiology ; Parasympathetic Nervous System/*physiology ; Sacrum/*innervation/*physiology ; }, abstract = {A recent developmental study of gene expression by Espinosa-Medina, Brunet and colleagues sparked controversy by asserting a revised nomenclature for divisions of the autonomic motor system. Should we re-classify the sacral autonomic outflow as sympathetic, as now suggested, or does it rightly belong to the parasympathetic system, as defined by Langley nearly 100 years ago? Arguments for rejecting Espinosa-Medina, Brunet et al.'s scheme subsequently appeared in e-letters and brief reviews. A more recent commentary in this journal by Brunet and colleagues responded to these criticisms by labeling Langley's scheme as a historical myth perpetuated by ignorance. In reaction to this heated exchange, I now examine both sides to the controversy, together with purported errors by the pioneers in the field. I then explain, once more, why the sacral outflow should remain known as parasympathetic, and outline suggestions for future experimentation to advance the understanding of cellular identity in the autonomic motor system.}, } @article {pmid29448790, year = {2018}, author = {Claudot, J and Kim, WJ and Dixit, A and Kim, H and Gould, T and Rocca, D and Lebègue, S}, title = {Benchmarking several van der Waals dispersion approaches for the description of intermolecular interactions.}, journal = {The Journal of chemical physics}, volume = {148}, number = {6}, pages = {064112}, doi = {10.1063/1.5018818}, pmid = {29448790}, issn = {1089-7690}, abstract = {Seven methods, including three van der Waals density functionals (vdW-DFs) and four different variants of the Tkatchenko-Scheffler (TS) methods, are tested on the A24, L7, and Taylor et al.'s "blind" test sets. It is found that for these systems, the vdW-DFs perform better that the TS methods. In particular, the vdW-DF-cx functional gives binding energies that are the closest to the reference values, while the many-body correction of TS does not always lead to an improvement in the description of molecular systems. In light of these results, several directions for further improvements to describe van der Waals interactions are discussed.}, } @article {pmid29448447, year = {2018}, author = {Juhász, R and Iglói, F}, title = {Nonuniversal and anomalous critical behavior of the contact process near an extended defect.}, journal = {Physical review. E}, volume = {97}, number = {1-1}, pages = {012111}, doi = {10.1103/PhysRevE.97.012111}, pmid = {29448447}, issn = {2470-0053}, abstract = {We consider the contact process near an extended surface defect, where the local control parameter deviates from the bulk one by an amount of λ(l)-λ(∞)=Al^{-s}, with l being the distance from the surface. We concentrate on the marginal situation s=1/ν_{⊥}, where ν_{⊥} is the critical exponent of the spatial correlation length, and study the local critical properties of the one-dimensional model by Monte Carlo simulations. The system exhibits a rich surface critical behavior. For weaker local activation rates AA_{c}, the phase transition is of mixed order: the surface order parameter is discontinuous; at the same time the temporal correlation length diverges algebraically as the critical point is approached, but with different exponents on the two sides of the transition. The mixed-order transition regime is analogous to that observed recently at a multiple junction and can be explained by the same type of scaling theory.}, } @article {pmid29425255, year = {2017}, author = {Kirchengast, S}, title = {Response to Lea et al.'s developmental plasticity: Bridging research in evolution and human health.}, journal = {Evolution, medicine, and public health}, volume = {2017}, number = {1}, pages = {181-182}, pmid = {29425255}, issn = {2050-6201}, support = {P30 AG024361/AG/NIA NIH HHS/United States ; }, } @article {pmid29415836, year = {2017}, author = {Itoi, A and Yamada, Y and Yokoyama, K and Adachi, T and Kimura, M}, title = {Validity of predictive equations for resting metabolic rate in healthy older adults.}, journal = {Clinical nutrition ESPEN}, volume = {22}, number = {}, pages = {64-70}, doi = {10.1016/j.clnesp.2017.08.010}, pmid = {29415836}, issn = {2405-4577}, mesh = {Aged ; Aged, 80 and over ; Asian People ; *Basal Metabolism ; Body Height ; Body Mass Index ; Body Weight ; Calorimetry, Indirect ; Cohort Studies ; Energy Metabolism ; Female ; Humans ; Japan ; Male ; Middle Aged ; Predictive Value of Tests ; }, abstract = {BACKGROUND & AIMS: Accurate estimation of energy expenditure in older people is important for nutritional support. The current literature contains controversial or inconsistent data regarding the resting metabolic rate (RMR, or basal metabolic rate) in older adults, including the relationship between the RMR and ethnicity. Little information about the RMR in healthy Asian older adults is available. This study was performed to examine the RMR in healthy Japanese older adults and compare it with previously established 16 equations.

METHODS: Thirty-two community-dwelling, healthy, and active elderly Japanese adults were enrolled (age, 64-87 years; 14 men, 18 women; mean height, 154.9 ± 8.9 cm; mean weight, 53.5 ± 9.1 kg; mean body mass index, 22.2 ± 2.5 kg/m[2]). The RMR was measured by indirect calorimetry. The measured RMR was compared among 16 equations. Correlation analysis, a paired t test, and a Bland-Altman plot were used to assess the agreement among the equations.

RESULTS: The average RMR was 1132 ± 178 kcal/day with 2233 ± 437 kcal/day average total energy expenditure (TEE) measured by doubly labeled water (DLW). The smallest bias was established by De Lorenzo et al.'s equation as bias ±1.96SD = 4 ± 121 kcal/day. De Lorenzo et al. and Ikeda et al.'s equations had no significant average bias both in men and women (P > 0.05). The 1.96SD of bias in six equations was within 160 kcal/day. In contrast, residuals between the measured and predicted RMR were largely correlated with the RMR in four equations. A sex-related difference in the mean bias was observed in many equations.

CONCLUSION: Although the average Japanese healthy older adult has a shorter stature and lower weight than older adults in the Western population, the current data suggest that a similar predictive equation for the RMR can be applied to both Japanese and Western older adults. This study demonstrate that the De Lorenzo et al.'s or Ikeda's equation may be useful for estimating RMR in the community-dwelling, healthy, and active elderly Japanese adults without any systematic bias.}, } @article {pmid29410633, year = {2017}, author = {Bader, M}, title = {The Limited Role of Number of Nested Syntactic Dependencies in Accounting for Processing Cost: Evidence from German Simplex and Complex Verbal Clusters.}, journal = {Frontiers in psychology}, volume = {8}, number = {}, pages = {2268}, pmid = {29410633}, issn = {1664-1078}, abstract = {This paper presents three acceptability experiments investigating German verb-final clauses in order to explore possible sources of sentence complexity during human parsing. The point of departure was De Vries et al.'s (2011) generalization that sentences with three or more crossed or nested dependencies are too complex for being processed by the human parsing mechanism without difficulties. This generalization is partially based on findings from Bach et al. (1986) concerning the acceptability of complex verb clusters in German and Dutch. The first experiment tests this generalization by comparing two sentence types: (i) sentences with three nested dependencies within a single clause that contains three verbs in a complex verb cluster; (ii) sentences with four nested dependencies distributed across two embedded clauses, one center-embedded within the other, each containing a two-verb cluster. The results show that sentences with four nested dependencies are judged as acceptable as control sentences with only two nested dependencies, whereas sentences with three nested dependencies are judged as only marginally acceptable. This argues against De Vries et al.'s (2011) claim that the human parser can process no more than two nested dependencies. The results are used to refine the Verb-Cluster Complexity Hypothesis of Bader and Schmid (2009a). The second and the third experiment investigate sentences with four nested dependencies in more detail in order to explore alternative sources of sentence complexity: the number of predicted heads to be held in working memory (storage cost in terms of the Dependency Locality Theory [DLT], Gibson, 2000) and the length of the involved dependencies (integration cost in terms of the DLT). Experiment 2 investigates sentences for which storage cost and integration cost make conflicting predictions. The results show that storage cost outweighs integration cost. Experiment 3 shows that increasing integration cost in sentences with two degrees of center embedding leads to decreased acceptability. Taken together, the results argue in favor of a multifactorial account of the limitations on center embedding in natural languages.}, } @article {pmid29409196, year = {2018}, author = {Canavese, F and Dimeglio, A and Bonnel, F}, title = {Postoperative CT-scan 3D reconstruction of the calcaneus following lateral calcaneal lengthening osteotomy for flatfoot deformity in children. Is the surgical procedure potentially associated with subtalar joint damage?.}, journal = {Foot and ankle surgery : official journal of the European Society of Foot and Ankle Surgeons}, volume = {24}, number = {5}, pages = {453-459}, doi = {10.1016/j.fas.2017.05.005}, pmid = {29409196}, issn = {1460-9584}, mesh = {Adolescent ; Bone Lengthening/*methods ; Calcaneus/diagnostic imaging/*surgery ; Child ; Female ; Flatfoot/diagnosis/*surgery ; Humans ; *Imaging, Three-Dimensional ; Male ; Osteotomy/*methods ; Postoperative Complications/diagnosis ; Preoperative Period ; Retrospective Studies ; Subtalar Joint/diagnostic imaging/*surgery ; Tomography, X-Ray Computed/*methods ; }, abstract = {BACKGROUND: Several anatomical studies have shown that the articular facets of the calcaneus can present with different anatomy. This study assessed the 3D anatomy of lateral calcaneal lengthening (LCL) osteotomy in relation to the anterior and middle facet of the calcaneus in a group of skeletally immature patients treated for symptomatic flatfoot deformity.

METHODS: During the study period, 14 consecutive patients (10 males, 4 females) presenting symptomatic flatfoot (20 feet) with different aetiologies underwent LCL osteotomy and CT scan with 3D reconstruction of the operated feet. Anatomy of articular factes of the calcaneus were graded according to Bunning & Barnett's classification. In order to assess clinical and functional outcome, all patients were evaluated according to Yoo et al.'s, Mosca's and AOFAS clinical criteria before surgery and at last follow-up visit.

RESULTS: Despite proving difficult to assess (10 out of 20 feet), dimensions of bone and joint structures revealed significant anatomical variations. In particular, working to Bunning & Barnett's classification, anatomy of the articular facet varied significantly among patients, and in Bunning & Barnett type-B1 or B2 the LCL osteotomy necessarily violates the articular surface of the anterior and middle facet of the calcaneus due to the fact that the two facets are fused together (single articular surface).

CONCLUSIONS: These biometric notions allow a better understanding of the impact on articular facets of the calcaneus of the osteotomy procedure suggested by Evans and Mosca. We anticipate that the findings reported here should lead to improved techniques for assessing all bone structures of the hindfoot, support logical classifications of the different pathological situations, and ultimately lead to improved treatment strategies.}, } @article {pmid29406142, year = {2018}, author = {Kaack, L and Bender, M and Finch, M and Borns, L and Grasham, K and Avolio, A and Clausen, S and Terese, NA and Johnstone, D and Williams, M}, title = {A Clinical Nurse Leader (CNL) practice development model to support integration of the CNL role into microsystem care delivery.}, journal = {Journal of professional nursing : official journal of the American Association of Colleges of Nursing}, volume = {34}, number = {1}, pages = {65-71}, doi = {10.1016/j.profnurs.2017.06.007}, pmid = {29406142}, issn = {1532-8481}, mesh = {Curriculum ; Delivery of Health Care/*organization & administration ; Humans ; *Leadership ; Nurse Clinicians/*standards ; *Staff Development ; United States ; United States Department of Veterans Affairs/organization & administration ; Veterans Health ; }, abstract = {The Veterans Health Administration (VHA) Office of Nursing Services (ONS) was an early adopter of Clinical Nurse Leader (CNL) practice, generating some of the earliest pilot data of CNL practice effectiveness. In 2011 the VHA ONS CNL Implementation & Evaluation Service (CNL I&E) piloted a curriculum to facilitate CNL transition to effective practice at local VHA settings. In 2015, the CNL I&E and local VHA setting stakeholders collaborated to refine the program, based on lessons learned at the national and local level. The workgroup reviewed the literature to identify theoretical frameworks for CNL practice and practice development. The workgroup selected Benner et al.'s Novice-to-Expert model as the defining framework for CNL practice development, and Bender et al.'s CNL Practice Model as the defining framework for CNL practice integration. The selected frameworks were cross-walked against existing curriculum elements to identify and clarify additional practice development needs. The work generated key insights into: core stages of transition to effective practice; CNL progress and expectations for each stage; and organizational support structures necessary for CNL success at each stage. The refined CNL development model is a robust tool that can be applied to support consistent and effective integration of CNL practice into care delivery.}, } @article {pmid29389191, year = {2018}, author = {Lupker, SJ and Nakayama, M and Yoshihara, M}, title = {Phonologically-based priming in the same-different task with L1 readers.}, journal = {Journal of experimental psychology. Learning, memory, and cognition}, volume = {44}, number = {8}, pages = {1317-1324}, doi = {10.1037/xlm0000515}, pmid = {29389191}, issn = {1939-1285}, support = {//Natural Sciences and Engineering Research Council of Canada/ ; //Japan Society for the Promotion of Science/ ; }, mesh = {Humans ; *Multilingualism ; Pattern Recognition, Visual ; Perceptual Masking ; *Phonetics ; *Reading ; *Repetition Priming ; }, abstract = {The present experiment provides an investigation of a promising new tool, the masked priming same-different task, for investigating the orthographic coding process. Orthographic coding is the process of establishing a mental representation of the letters and letter order in the word being read which is then used by readers to access higher-level (e.g., semantic) information about that word. Prior research (e.g., Norris & Kinoshita, 2008) had suggested that performance in this task may be based entirely on orthographic codes. As reported by Lupker, Nakayama, and Perea (2015a), however, in at least some circumstances, phonological codes also play a role. Specifically, even though their 2 languages are completely different orthographically, Lupker et al.'s Japanese-English bilinguals showed priming in this task when masked L1 primes were phonologically similar to L2 targets. An obvious follow-up question is whether Lupker et al.'s effect might have resulted from a strategy that was adopted by their bilinguals to aid in processing of, and memory for, the somewhat unfamiliar L2 targets. In the present experiment, Japanese readers responded to (Japanese) Kanji targets with phonologically identical primes (on "related" trials) being presented in a completely different but highly familiar Japanese script, Hiragana. Once again, significant priming effects were observed, indicating that, although performance in the masked priming same-different task may be mainly based on orthographic codes, phonological codes can play a role even when the stimuli being matched are familiar words from a reader's L1. (PsycINFO Database Record}, } @article {pmid29383457, year = {2018}, author = {Van Den Driessche, G and Fourches, D}, title = {Adverse drug reactions triggered by the common HLA-B*57:01 variant: virtual screening of DrugBank using 3D molecular docking.}, journal = {Journal of cheminformatics}, volume = {10}, number = {1}, pages = {3}, pmid = {29383457}, issn = {1758-2946}, abstract = {BACKGROUND: Idiosyncratic adverse drug reactions have been linked to a drug's ability to bind with a human leukocyte antigen (HLA) protein. However, due to the thousands of HLA variants and limited structural data for drug-HLA complexes, predicting a specific drug-HLA combination represents a significant challenge. Recently, we investigated the binding mode of abacavir with the HLA-B*57:01 variant using molecular docking. Herein, we developed a new ensemble screening workflow involving three X-ray crystal derived docking procedures to screen the DrugBank database and identify potentially HLA-B*57:01 liable drugs. Then, we compared our workflow's performance with another model recently developed by Metushi et al., which proposed seven in silico HLA-B*57:01 actives, but were later found to be experimentally inactive.

METHODS: After curation, there were over 6000 approved and experimental drugs remaining in DrugBank for docking using Schrodinger's GLIDE SP and XP scoring functions. Docking was performed with our new consensus-like ensemble workflow, relying on three different X-ray crystals (3VRI, 3VRJ, and 3UPR) in presence and absence of co-binding peptides. The binding modes of HLA-B*57:01 hit compounds for all three peptides were further explored using 3D interaction fingerprints and hierarchical clustering.

RESULTS: The screening resulted in 22 hit compounds forecasted to bind HLA-B*57:01 in all docking conditions (SP and XP with and without peptides P1, P2, and P3). These 22 compounds afforded 2D-Tanimoto similarities being less than 0.6 when compared to the structure of native abacavir, whereas their 3D binding mode similarities varied in a broader range (0.2-0.8). Hierarchical clustering using a Ward Linkage revealed different clustering patterns for each co-binding peptide. When we docked Metushi et al.'s seven proposed hits using our workflow, our screening platform identified six out of seven as being inactive. Molecular dynamic simulations were used to explore the stability of abacavir and acyclovir in complex with peptide P3.

CONCLUSIONS: This study reports on the extensive docking of the DrugBank database and the 22 HLA-B*57:01 liable candidates we identified. Importantly, comparisons between this study and the one by Metushi et al. highlighted new critical and complementary knowledge for the development of future HLA-specific in silico models.}, } @article {pmid29382340, year = {2018}, author = {Chandra-Mouli, V and Plesons, M and Sullivan, E and Gonsalves, L and Say, L}, title = {38.8 million additional modern contraceptive users: this, in fact, is "a never-before opportunity to strengthen investment and action on adolescent contraception".}, journal = {Reproductive health}, volume = {15}, number = {1}, pages = {17}, pmid = {29382340}, issn = {1742-4755}, support = {001/WHO_/World Health Organization/International ; }, mesh = {Adolescent ; Adolescent Health Services ; Contraception/*methods ; Contraception Behavior/*psychology ; Female ; Humans ; Pregnancy ; Pregnancy in Adolescence/*prevention & control ; Reproductive Health Services ; *Sex Education ; }, abstract = {BACKGROUND: We thank Bijlmakers et al. for their interest in our article, "A never-before opportunity to strengthen investment and action on adolescent contraception, and what we must do to make full use of it", and are grateful for the opportunity to respond to their four key assertions.

RESPONSE: First, we fully agree that sexual rights are controversial, which we discussed in depth in our original article. However, we reaffirm that there is global consensus on adolescent contraception as evidenced in part by recent data emerging from FP2020 on 38.8 million additional modern contraceptive users, the Global Goods and commitments emanating from the 2017 FP2020 summit, and their translated actions at the country level. Additionally, we clarify WHO's working definitions of sex, sexual health, and sexuality, and introduce WHO's newly released Operational Framework on Sexual Health and its Linkages to Reproductive Health. We welcome and agree with Bijlmakers et al.'s second point, which elaborates on the barrier of restrictive laws and policies. To address this barrier, we describe examples of resources that can help programmes understand the political/social context that drives these laws and policies at national and subnational levels, and identify programmatic gaps and best practices to address them within specific political/social contexts. We also welcome and agree with Bijlmakers et al.'s third point, which reiterates that discomfort around adolescent sexuality is a major barrier for sexuality education. In response, we point to four relevant reviews of CSE policies and their implementation, our original article's description of three programmes that have successfully addressed inadequate teacher skills, and our ongoing work on documenting strategies to build an enabling environment for CSE and deal with resistance. Lastly, we wholeheartedly agree that the harmful policies noted by Bijlmakers et al. are damaging to international efforts to improve adolescent SRH and rights. We argue, though, that these policies alone will not undermine efforts by countless other stakeholders around the world who are working in defence and promotion of adolescents' SRH and rights.

CONCLUSION: Despite the many valid obstacles noted by Bijlmakers et al., we truly believe that this is "a never-before opportunity to strengthen investment and action on adolescent contraception".}, } @article {pmid29379458, year = {2017}, author = {Glaman, R and Chen, Q}, title = {Measurement Invariance of a Classroom Engagement Measure among Academically At-Risk Students.}, journal = {Frontiers in psychology}, volume = {8}, number = {}, pages = {2345}, pmid = {29379458}, issn = {1664-1078}, abstract = {The current study investigated the measurement invariance of a classroom engagement measure across time points, genders, and ethnicities using a sample of 523 academically at-risk students across grades 7 through 9; this measure was based on Skinner et al.'s (1990) original engagement measure. The engagement measure was comprised of 16 items, yielding three factors: Behavioral Engagement, Behavioral Disaffection, and Emotional Engagement. Configural, metric, and scalar invariance held across the three time points, as did invariance of factor covariances and means, indicating that scores have a similar meaning across all 3 years. The engagement measure also featured adequate configural, metric, and scalar invariance, and invariance of factor covariances and means across genders and ethnicities. These findings suggest the measure is appropriate for investigating substantive hypotheses regarding classroom engagement across different grade levels, genders, and ethnicities. In summary, the current results indicate this measure of classroom engagement is suitable for testing hypotheses regarding group differences in engagement across grade levels, genders, and ethnicities. Researchers may also use this measure to examine relationships between the engagement factors and other important academic outcomes. Limitations of the current study, such as certain caveats regarding convergent validity and internal consistency, are also discussed.}, } @article {pmid29370832, year = {2018}, author = {Pugh, P and Hemingway, P and Christian, M and Higginbottom, G}, title = {Children's, parents' and other stakeholders' perspectives on early dietary self-management to delay disease progression of chronic disease in children: a protocol for a mixed studies systematic review with a narrative synthesis.}, journal = {Systematic reviews}, volume = {7}, number = {1}, pages = {20}, pmid = {29370832}, issn = {2046-4053}, mesh = {Adolescent ; Caregivers/psychology ; Child ; *Chronic Disease ; Diet, Healthy/*methods ; *Disease Progression ; Humans ; Parents/*psychology ; *Self-Management ; Systematic Reviews as Topic ; }, abstract = {BACKGROUND: Chronic disease of childhood may be delayed by early dietary intervention. The purpose of this systematic review is to provide decision-makers with a perspective on the role of early dietary intervention, as a form of self-management, to delay disease progression in children with early chronic disease, as described by children, parents and other stakeholders.

METHODS: The study will systematically review empirical research (qualitative, quantitative and mixed method designs), including grey literature, using a narrative synthesis. A four-stage search process will be conducted involving a scoping search, the Scottish Intercollegiate Guidelines Network (SIGN) Patient Issues search filter on MEDLINE, the search of seven databases using a chronic disease and chronic kidney disease (CKD) search strategy, and hand searching the reference lists of identified papers for additional studies. All studies retrieved during the search process will undergo a screening and selection process against the inclusion/exclusion criteria. Methodological quality of relevant studies will be assessed using a validated Mixed Studies Review scoring system, before inclusion in the review. Relevant grey literature will be assessed for methodological quality and relative importance using McGrath et al.'s framework and the Academy Health advisory committee categories, respectively. Data extraction will be guided by the Centre for Review and Dissemination guidance and Popay et al.'s work. The narrative synthesis of the findings will use elements of Popay et al.'s methodology of narrative synthesis, applying recognised tools for each of the four elements: (1) developing a theory of how the intervention works, why and for whom; (2) developing a preliminary synthesis of findings of included studies; (3) exploring relationships in the data; and (4) assessing the robustness of the synthesis.

DISCUSSION: This mixed studies systematic review with a narrative synthesis seeks to elucidate the gaps in current knowledge and generate a fresh explanation of research findings on early dietary self-management in chronic disease, with particular application to CKD, from the stakeholders' perspective. The review will provide an important platform to inform future research, identifying the facilitators and barriers to implementing early dietary interventions. Ultimately, the review will contribute vital information to inform future improvements in chronic disease. The lead author has a particular interest in CKD paediatric service delivery.

The review has been registered with PROSPERO (CRD42017078130).}, } @article {pmid29359482, year = {2018}, author = {Phillips, JM and Stalter, AM and Winegardner, S and Wiggs, C and Jauch, A}, title = {Systems thinking and incivility in nursing practice: An integrative review.}, journal = {Nursing forum}, volume = {}, number = {}, pages = {}, doi = {10.1111/nuf.12250}, pmid = {29359482}, issn = {1744-6198}, abstract = {BACKGROUND AND PURPOSE: There is a critical need for nurses and interprofessional healthcare providers to implement systems thinking (ST) across international borders, addressing incivility and its perilous effects on patient quality and safety. An estimated one million patients die in hospitals worldwide due to avoidable patient-related errors. Establishing safe and civil workplaces using ST is paramount to promoting clear, level-headed thinking from which patient-centered nursing actions can impact health systems. The purpose of the paper is to answer the research question, What ST evidence fosters the effect of workplace civility in practice settings?

METHODS: Whittemore and Knafl's integrative review method guided this study. The quality of articles was determined using Chu et al.'s Mixed Methods Assessment Tool.

RESULTS: Thirty-eight studies were reviewed. Themes emerged describing antecedents and consequences of incivility as embedded within complex systems, suggesting improvements for civility and systems/ST in nursing practice.

IMPLICATIONS FOR PRACTICE: This integrative review provides information about worldwide incivility in nursing practice from a systems perspective. Several models are offered as a means of promoting civility in nursing practice to improve patient quality and safety. Further study is needed regarding incivility and resultant effects on patient quality and safety.}, } @article {pmid29354078, year = {2017}, author = {Masip, J and Martínez, C and Blandón-Gitlin, I and Sánchez, N and Herrero, C and Ibabe, I}, title = {Learning to Detect Deception from Evasive Answers and Inconsistencies across Repeated Interviews: A Study with Lay Respondents and Police Officers.}, journal = {Frontiers in psychology}, volume = {8}, number = {}, pages = {2207}, pmid = {29354078}, issn = {1664-1078}, abstract = {Previous research has shown that inconsistencies across repeated interviews do not indicate deception because liars deliberately tend to repeat the same story. However, when a strategic interview approach that makes it difficult for liars to use the repeat strategy is used, both consistency and evasive answers differ significantly between truth tellers and liars, and statistical software (binary logistic regression analyses) can reach high classification rates (Masip et al., 2016b). Yet, if the interview procedure is to be used in applied settings the decision process will be made by humans, not statistical software. To address this issue, in the current study, 475 college students (Experiment 1) and 142 police officers (Experiment 2) were instructed to code and use consistency, evasive answers, or a combination or both before judging the veracity of Masip et al.'s (2016b) interview transcripts. Accuracy rates were high (60% to over 90%). Evasive answers yielded higher rates than consistency, and the combination of both these cues produced the highest accuracy rates in identifying both truthful and deceptive statements. Uninstructed participants performed fairly well (around 75% accuracy), apparently because they spontaneously used consistency and evasive answers. The pattern of results was the same among students, all officers, and veteran officers only, and shows that inconsistencies between interviews and evasive answers reveal deception when a strategic interview approach that hinders the repeat strategy is used.}, } @article {pmid29342805, year = {2017}, author = {Weisberg, DS and Friend, S}, title = {Embracing nonfiction: How to extend the Distancing-Embracing model.}, journal = {The Behavioral and brain sciences}, volume = {40}, number = {}, pages = {e379}, doi = {10.1017/S0140525X17001881}, pmid = {29342805}, issn = {1469-1825}, mesh = {*Emotions ; }, abstract = {The Distancing factor of Menninghaus et al.'s model includes schemas that remind consumers that the representation is fictional. Although they claim that these schemas are crucial to the functioning of the Embracing factor of the model, we argue that consumers can have similar responses to nonfictional representations. We urge the authors to expand their model to include such cases.}, } @article {pmid29342702, year = {2017}, author = {Livesey, EJ and Goldwater, MB and Colagiuri, B}, title = {Will human-like machines make human-like mistakes?.}, journal = {The Behavioral and brain sciences}, volume = {40}, number = {}, pages = {e270}, doi = {10.1017/S0140525X1700019X}, pmid = {29342702}, issn = {1469-1825}, mesh = {*Dissent and Disputes ; Humans ; *Learning ; }, abstract = {Although we agree with Lake et al.'s central argument, there are numerous flaws in the way people use causal models. Our models are often incorrect, resistant to correction, and applied inappropriately to new situations. These deficiencies are pervasive and have real-world consequences. Developers of machines with similar capacities should proceed with caution.}, } @article {pmid29342693, year = {2017}, author = {Marblestone, AH and Wayne, G and Kording, KP}, title = {Understand the cogs to understand cognition.}, journal = {The Behavioral and brain sciences}, volume = {40}, number = {}, pages = {e272}, doi = {10.1017/S0140525X17000218}, pmid = {29342693}, issn = {1469-1825}, mesh = {Brain ; *Cognition ; Humans ; *Learning ; Thinking ; }, abstract = {Lake et al. suggest that current AI systems lack the inductive biases that enable human learning. However, Lake et al.'s proposed biases may not directly map onto mechanisms in the developing brain. A convergence of fields may soon create a correspondence between biological neural circuits and optimization in structured architectures, allowing us to systematically dissect how brains learn.}, } @article {pmid29342692, year = {2017}, author = {Forbus, KD and Gentner, D}, title = {Evidence from machines that learn and think like people.}, journal = {The Behavioral and brain sciences}, volume = {40}, number = {}, pages = {e264}, doi = {10.1017/S0140525X17000139}, pmid = {29342692}, issn = {1469-1825}, mesh = {*Cognition ; Humans ; *Thinking ; }, abstract = {We agree with Lake et al.'s trenchant analysis of deep learning systems, including that they are highly brittle and that they need vastly more examples than do people. We also agree that human cognition relies heavily on structured relational representations. However, we differ in our analysis of human cognitive processing. We argue that (1) analogical comparison processes are central to human cognition; and (2) intuitive physical knowledge is captured by qualitative representations, rather than quantitative simulations.}, } @article {pmid29342688, year = {2017}, author = {Clegg, JM and Corriveau, KH}, title = {Children begin with the same start-up software, but their software updates are cultural.}, journal = {The Behavioral and brain sciences}, volume = {40}, number = {}, pages = {e260}, doi = {10.1017/S0140525X17000097}, pmid = {29342688}, issn = {1469-1825}, mesh = {Child ; Humans ; *Learning ; Software ; *Thinking ; }, abstract = {We propose that early in ontogeny, children's core cognitive abilities are shaped by culturally dependent "software updates." The role of sociocultural inputs in the development of children's learning is largely missing from Lake et al.'s discussion of the development of human-like artificial intelligence, but its inclusion would help move research even closer to machines that can learn and think like humans.}, } @article {pmid29342664, year = {2017}, author = {Hauser, MD}, title = {Of mice and men, nature and nurture, and a few red herrings.}, journal = {The Behavioral and brain sciences}, volume = {40}, number = {}, pages = {e204}, doi = {10.1017/S0140525X16001643}, pmid = {29342664}, issn = {1469-1825}, mesh = {Animals ; *Intelligence ; }, abstract = {Burkart et al.'s proposal is based on three false premises: (1) theories of the mind are either domain-specific/modular (DSM) or domain-general (DG); (2) DSM systems are considered inflexible, built by nature; and (3) animal minds are deemed as purely DSM. Clearing up these conceptual confusions is a necessary first step in understanding how general intelligence evolved.}, } @article {pmid29342662, year = {2017}, author = {Lewis, DMG and Al-Shawaf, L and Anderson, M}, title = {Contemporary evolutionary psychology and the evolution of intelligence.}, journal = {The Behavioral and brain sciences}, volume = {40}, number = {}, pages = {e210}, doi = {10.1017/S0140525X16001692}, pmid = {29342662}, issn = {1469-1825}, mesh = {*Biological Evolution ; *Intelligence ; Research ; }, abstract = {Burkart et al.'s impressive synthesis will serve as a valuable resource for intelligence research. Despite its strengths, the target article falls short of offering compelling explanations for the evolution of intelligence. Here, we outline its shortcomings, illustrate how these can lead to misguided conclusions about the evolution of intelligence, and suggest ways to address the article's key questions.}, } @article {pmid29342655, year = {2017}, author = {Buskell, A and Halina, M}, title = {Domains of generality.}, journal = {The Behavioral and brain sciences}, volume = {40}, number = {}, pages = {e200}, doi = {10.1017/S0140525X16001606}, pmid = {29342655}, issn = {1469-1825}, mesh = {*Intelligence ; }, abstract = {We argue that general intelligence, as presented in the target article, generates multiple distinct and non-equivalent characterisations. Clarifying this central concept is necessary for assessing Burkart et al.'s proposal that the cultural intelligence hypothesis is the best explanation for the evolution of general intelligence. We assess this claim by considering two characterisations of general intelligence presented in the article.}, } @article {pmid29342653, year = {2017}, author = {Sidney, PG and Thompson, CA and Matthews, PG and Hubbard, EM}, title = {From continuous magnitudes to symbolic numbers: The centrality of ratio.}, journal = {The Behavioral and brain sciences}, volume = {40}, number = {}, pages = {e190}, doi = {10.1017/S0140525X16002284}, pmid = {29342653}, issn = {1469-1825}, support = {R03 HD081087/HD/NICHD NIH HHS/United States ; }, mesh = {*Cognition ; Language ; *Mathematics ; }, abstract = {Leibovich et al.'s theory neither accounts for the deep connections between whole numbers and other classes of number nor provides a potential mechanism for mapping continuous magnitudes to symbolic numbers. We argue that focusing on non-symbolic ratio processing abilities can furnish a more expansive account of numerical cognition that remedies these shortcomings.}, } @article {pmid29342643, year = {2017}, author = {Margolis, E}, title = {Infants, animals, and the origins of number.}, journal = {The Behavioral and brain sciences}, volume = {40}, number = {}, pages = {e178}, doi = {10.1017/S0140525X16002168}, pmid = {29342643}, issn = {1469-1825}, mesh = {Animals ; *Cognition ; Humans ; Infant ; Infant, Newborn ; *Vision, Ocular ; }, abstract = {Where do human numerical abilities come from? Leibovich et al. argue against nativist views of numerical development noting limitations in newborns' vision and limitations regarding newborns' ability to individuate objects. I argue that these considerations do not undermine competing nativist views and that Leibovich et al.'s model itself presupposes that infant learners have numerical representations.}, } @article {pmid29342640, year = {2017}, author = {Rubinsten, O and Karni, A}, title = {Innateness of magnitude perception? Skill can be acquired and mastered at all ages.}, journal = {The Behavioral and brain sciences}, volume = {40}, number = {}, pages = {e186}, doi = {10.1017/S0140525X16002247}, pmid = {29342640}, issn = {1469-1825}, mesh = {Aptitude ; *Cognition ; *Perception ; }, abstract = {We agree with Leibovich et al.'s argument that the number sense theory should be re-evaluated. However, we argue that highly efficient skills (i.e., fluent and highly accurate, "automatic," performance) can be acquired and mastered at all ages. Hence, evidence for primacy or fluency in perceiving continuous magnitudes is insufficient for supporting strong conclusions about the innateness of this aptitude.}, } @article {pmid29342578, year = {2017}, author = {Ert, E and Heiman, A}, title = {Potential psychological accounts for the relation between food insecurity and body overweight.}, journal = {The Behavioral and brain sciences}, volume = {40}, number = {}, pages = {e117}, doi = {10.1017/S0140525X16001424}, pmid = {29342578}, issn = {1469-1825}, mesh = {*Food Supply ; Humans ; *Obesity ; Overweight ; }, abstract = {We suggest two psychological mechanisms, temporal discounting and feeling of resource scarcity, for explaining the relation between food insecurity and body overweight. We demonstrate how Nettle et al.'s findings could be explained, post hoc, by each of these accounts, suggesting that their data are not rich enough to allow identification of mechanisms that underlie food insecurity and overweight relationship.}, } @article {pmid29342577, year = {2017}, author = {Dittmann, AG and Maner, JK}, title = {A life-history theory perspective on obesity.}, journal = {The Behavioral and brain sciences}, volume = {40}, number = {}, pages = {e115}, doi = {10.1017/S0140525X16001400}, pmid = {29342577}, issn = {1469-1825}, mesh = {Biological Evolution ; *Food Supply ; Humans ; *Obesity ; }, abstract = {We extend Nettle et al.'s insurance hypothesis (IH) argument, drawing upon life-history theory (LHT), a developmental evolutionary perspective that documents downstream consequences of early-life exposure to unpredictable environments. We discuss novel evidence consistent with both IH and LHT, suggesting that early-life exposure to unpredictable environments is associated with reduced engagement in weight management behaviors and a greater probability of adulthood obesity.}, } @article {pmid29342572, year = {2017}, author = {Chen, BB}, title = {The life history model of the insurance hypothesis.}, journal = {The Behavioral and brain sciences}, volume = {40}, number = {}, pages = {e111}, doi = {10.1017/S0140525X16001369}, pmid = {29342572}, issn = {1469-1825}, mesh = {Adult ; Body Mass Index ; Child ; Female ; *Food Supply ; Humans ; Male ; *Obesity ; }, abstract = {Nettle et al.'s explanation based on the insurance hypothesis applies only to the association between food insecurity and body weight among adult women, but not to the results about there being no such associations among adult men and children. These results may be best understood when the insurance hypothesis is integrated with the life history model.}, } @article {pmid29342564, year = {2017}, author = {van der Linden, SL}, title = {The role of climate in human aggression and violence: Towards a broader conception.}, journal = {The Behavioral and brain sciences}, volume = {40}, number = {}, pages = {e99}, doi = {10.1017/S0140525X16001230}, pmid = {29342564}, issn = {1469-1825}, mesh = {*Aggression ; Climate ; Humans ; *Self-Control ; Self-Injurious Behavior ; Violence ; }, abstract = {The psychological processes that predict aggressive behaviour are also typically associated with violent self-harm (e.g., poor self-control). Yet, although human violence (towards others) appears to increase with proximity to the equator, suicide rates tend to decrease. In the light of this empirical puzzle, I argue that Van Lange et al.'s CLASH model would benefit from a broader conceptualization of human aggression.}, } @article {pmid29342557, year = {2017}, author = {Cabeza de Baca, T and Hertler, SC and Dunkel, CS}, title = {Reply to Van Lange et al.: Proximate and ultimate distinctions must be made to the CLASH model.}, journal = {The Behavioral and brain sciences}, volume = {40}, number = {}, pages = {e81}, doi = {10.1017/S0140525X16001175}, pmid = {29342557}, issn = {1469-1825}, mesh = {Acclimatization ; *Aggression ; Humans ; *Self-Control ; Violence ; }, abstract = {Transcending reviewed proximate theories, Van Lange et al.'s CLASH model attempts to ultimately explain the poleward declension of aggression and violence. Seasonal cold is causal, but, we contend, principally as an ecologically relevant evolutionary pressure. We further argue that futurity and restraint are life history variables, and that Life History Theory evolutionarily explains the biogeography of aggression and violence as strategic adaptation.}, } @article {pmid29342555, year = {2017}, author = {Van de Vliert, E and Daan, S}, title = {Hell on earth? Equatorial peaks of heat, poverty, and aggression.}, journal = {The Behavioral and brain sciences}, volume = {40}, number = {}, pages = {e98}, doi = {10.1017/S0140525X16001114}, pmid = {29342555}, issn = {1469-1825}, mesh = {*Aggression ; Hot Temperature ; Humans ; Poverty ; *Self-Control ; Violence ; }, abstract = {Van Lange et al.'s global CLASH model overemphasizes climatic origins and underemphasizes economic origins of aggression. Our 167-country analysis of latitudinal gradients of heat, poverty, and aggression finds that heat-induced aggression is mediated by poverty and that heat tempers rather than fuels poverty-induced aggression. More importantly, the CLASH model hints at latitudinal, equatorial, and hemispheric upgradings of climato-economic modeling of human behavior.}, } @article {pmid29340780, year = {2018}, author = {Domenech, C and Altamura, C and Bernasconi, C and Corral, R and Elkis, H and Evans, J and Malla, A and Krebs, MO and Nordstroem, AL and Zink, M and Haro, JM}, title = {Health-related quality of life in outpatients with schizophrenia: factors that determine changes over time.}, journal = {Social psychiatry and psychiatric epidemiology}, volume = {53}, number = {3}, pages = {239-248}, pmid = {29340780}, issn = {1433-9285}, support = {Data base freely provided by Roche//F. Hoffmann-La Roche/International ; }, mesh = {Adolescent ; Adult ; Depression/psychology ; Female ; Humans ; Male ; Middle Aged ; Outpatients/*psychology ; Quality of Life/*psychology ; Regression Analysis ; *Schizophrenic Psychology ; Sex Factors ; Surveys and Questionnaires ; Time Factors ; Young Adult ; }, abstract = {PURPOSE: The objective of this study was to analyze the clinical factors associated with changes in HRQoL in outpatients with schizophrenia using both generic and condition-specific HRQoL scales.

METHODS: Adult outpatients with schizophrenia at least 18 years of age who did not have an acute psychotic exacerbation in the 3 months prior to baseline were recruited. PANSS dimensions were calculated based on Lindenmayer et al.'s five factors. HRQoL data were assessed by patients using the Schizophrenia Quality of Life Scale (SQLS), the Short Form-36 (SF-36), and the EuroQol-5 Dimension (EQ-5D) questionnaires.

RESULTS: Out of the 1345 patients included at baseline, 1196 (89%) were evaluated at 12 months. Regression models showed that the factor most consistently associated with HRQoL at endpoint was change in the PANSS negative symptoms score. A decrease in the PANSS negative symptoms score from baseline to 1 year was associated with a decrease in HRQoL during the same period. There were also significant associations of the change in PANSS excitatory factor with all the HRQoL scales except the SF-36 PCS. Female gender was associated with a decrease in all HRQoL ratings. There was also a relationship between years since onset and HRQoL. The longer the time since illness onset, the larger the decrease in HRQoL.

CONCLUSIONS: This study has found that, in outpatients with schizophrenia, changes in negative and excitement symptoms may have a greater an association with HRQoL than changes in positive, cognitive and depressive symptoms.}, } @article {pmid29333056, year = {2017}, author = {Harris, LN and Perfetti, C}, title = {Individual Differences in Phonological Feedback Effects: Evidence for the Orthographic Recoding Hypothesis of Orthographic Learning.}, journal = {Scientific studies of reading : the official journal of the Society for the Scientific Study of Reading}, volume = {21}, number = {1}, pages = {31-45}, pmid = {29333056}, issn = {1088-8438}, support = {R01 HD058566/HD/NICHD NIH HHS/United States ; }, abstract = {Share (1995) has proposed phonological recoding (the translation of letters into sounds) as a self-teaching mechanism through which readers establish complete lexical representations. More recently, McKague et al. (2008) proposed a similar role for orthographic recoding, i.e., feedback from sounds to letters, in building and refining lexical representations. We reasoned that an interaction between feedback consistency measures and spelling ability in a spelling decision experiment would lend support to this hypothesis. In a linear mixed effects logistic regression of accuracy data this interaction was significant. Better spellers but not poorer spellers were immune to feedback effects in deciding if a word is spelled correctly, which is consistent with McKague et al.'s prediction that the impact of phonological feedback on word recognition will diminish when the orthographic representation for an item is fully specified. The study demonstrates the importance of considering individual differences when investigating the role of phonology in reading.}, } @article {pmid29331683, year = {2018}, author = {Springer, MS and Murphy, WJ and Roca, AL}, title = {Appropriate fossil calibrations and tree constraints uphold the Mesozoic divergence of solenodons from other extant mammals.}, journal = {Molecular phylogenetics and evolution}, volume = {121}, number = {}, pages = {158-165}, doi = {10.1016/j.ympev.2018.01.007}, pmid = {29331683}, issn = {1095-9513}, mesh = {Animals ; Calibration ; Cuba ; Evolution, Molecular ; *Fossils ; Mammals/*classification ; *Phylogeny ; Time Factors ; }, abstract = {The mammalian order Eulipotyphla includes four extant families of insectivorans: Solenodontidae (solenodons); Talpidae (moles); Soricidae (shrews); and Erinaceidae (hedgehogs). Of these, Solenodontidae includes only two extant species, which are endemic to the largest islands of the Greater Antilles: Cuba and Hispaniola. Most molecular studies suggest that eulipotyphlan families diverged from each other across several million years, with the basal split between Solenodontidae and other families occurring in the Late Cretaceous. By contrast, Sato et al. (2016) suggest that eulipotyphlan families diverged from each other in a polytomy ∼58.6 million years ago (Mya). This more recent divergence estimate for Solenodontidae versus other extant eulipotyphlans suggests that solenodons must have arrived in the Greater Antilles via overwater dispersal rather than vicariance. Here, we show that the young timetree estimates for eulipotyphlan families and the polytomy are due to an inverted ingroup-outgroup arrangement of the tree, the result of using Tracer rather than TreeAnnotator to compile interfamilial divergence times, and of not enforcing the monophly of well-established clades such as Laurasiatheria and Eulipotyphla. Finally, Sato et al.'s (2016) timetree includes several zombie lineages where estimated divergence times are much younger than minimum ages that are implied by the fossil record. We reanalyzed Sato et al.'s (2016) original data with enforced monophyly for well-established clades and updated fossil calibrations that eliminate the inference of zombie lineages. Our resulting timetrees, which were compiled with TreeAnnotator rather than Tracer, produce dates that are in good agreement with other recent studies and place the basal split between Solenodontidae and other eulipotyphlans in the Late Cretaceous.}, } @article {pmid29327631, year = {2019}, author = {Ma, Z and Bayley, MT and Perrier, L and Dhir, P and Dépatie, L and Comper, P and Ruttan, L and Lay, C and Munce, SEP}, title = {The association between adverse childhood experiences and adult traumatic brain injury/concussion: a scoping review.}, journal = {Disability and rehabilitation}, volume = {41}, number = {11}, pages = {1360-1366}, doi = {10.1080/09638288.2018.1424957}, pmid = {29327631}, issn = {1464-5165}, mesh = {Adult ; *Adult Survivors of Child Adverse Events/psychology/statistics & numerical data ; *Adverse Childhood Experiences ; *Brain Injuries, Traumatic/psychology/rehabilitation ; Humans ; *Mental Disorders/epidemiology/psychology ; Risk Factors ; }, abstract = {BACKGROUND: Adverse childhood experiences are significant risk factors for physical and mental illnesses in adulthood. Traumatic brain injury/concussion is a challenging condition where pre-injury factors may affect recovery. The association between childhood adversity and traumatic brain injury/concussion has not been previously reviewed. The research question addressed is: What is known from the existing literature about the association between adverse childhood experiences and traumatic brain injury/concussion in adults?

METHODS: All original studies of any type published in English since 2007 on adverse childhood experiences and traumatic brain injury/concussion outcomes were included. The literature search was conducted in multiple electronic databases. Arksey and O'Malley and Levac et al.'s scoping review frameworks were used. Two reviewers independently completed screening and data abstraction.

RESULTS: The review yielded six observational studies. Included studies were limited to incarcerated or homeless samples, and individuals at high-risk of or with mental illnesses. Across studies, methods for childhood adversity and traumatic brain injury/concussion assessment were heterogeneous.

DISCUSSION: A positive association between adverse childhood experiences and traumatic brain injury occurrence was identified. The review highlights the importance of screening and treatment of adverse childhood experiences. Future research should extend to the general population and implications on injury recovery. Implications for rehabilitation Exposure to adverse childhood experiences is associated with increased risk of traumatic brain injury. Specific types of adverse childhood experiences associated with risk of traumatic brain injury include childhood physical abuse, psychological abuse, household member incarceration, and household member drug abuse. Clinicians and researchers should inquire about adverse childhood experiences in all people with traumatic brain injury as pre-injury health conditions can affect recovery.}, } @article {pmid29327331, year = {2018}, author = {Paeye, C and Collins, T and Cavanagh, P and Herwig, A}, title = {Calibration of peripheral perception of shape with and without saccadic eye movements.}, journal = {Attention, perception & psychophysics}, volume = {80}, number = {3}, pages = {723-737}, doi = {10.3758/s13414-017-1478-3}, pmid = {29327331}, issn = {1943-393X}, support = {ERC Grant Agreement No. AG324070 (to PC)//European Research Council/International ; Grant He6388/1-2 (to AH)//Deutsche Forschungsgemeinschaft/ ; }, mesh = {Adult ; Calibration ; Female ; Fovea Centralis ; Humans ; Judgment ; Learning ; Male ; Pattern Recognition, Visual/*physiology ; Photic Stimulation/methods ; Saccades/*physiology ; Young Adult ; }, abstract = {The cortical representations of a visual object differ radically across saccades. Several studies claim that the visual system adapts the peripheral percept to better match the subsequent foveal view. Recently, Herwig, Weiß, and Schneider (2015, Annals of the New York Academy of Sciences, 1339(1), 97-105) found that the perception of shape demonstrates a saccade-dependent learning effect. Here, we ask whether this learning actually requires saccades. We replicated Herwig et al.'s (2015) study and introduced a fixation condition. In a learning phase, participants were exposed to objects whose shape systematically changed during a saccade, or during a displacement from peripheral to foveal vision (without a saccade). In a subsequent test, objects were perceived as less (more) curved if they previously changed from more circular (triangular) in the periphery to more triangular (circular) in the fovea. Importantly, this pattern was seen both with and without saccades. We then tested whether a variable delay between the presentations of the peripheral and foveal objects would affect their association-hypothetically weakening it at longer delays. Again, we found that shape judgments depended on the changes experienced during the learning phase and that they were similar in both the saccade and fixation conditions. Surprisingly, they were not affected by the delay between the peripheral and foveal presentations over the range we tested. These results suggest that a general associative process, independent of saccade execution, contributes to the perception of shape across viewpoints.}, } @article {pmid29323501, year = {2018}, author = {Giampietro, R and Spinelli, F and Contino, M and Colabufo, NA}, title = {The Pivotal Role of Copper in Neurodegeneration: A New Strategy for the Therapy of Neurodegenerative Disorders.}, journal = {Molecular pharmaceutics}, volume = {15}, number = {3}, pages = {808-820}, doi = {10.1021/acs.molpharmaceut.7b00841}, pmid = {29323501}, issn = {1543-8392}, mesh = {Animals ; Brain Chemistry/*drug effects ; Chelating Agents/pharmacology/*therapeutic use ; Copper/metabolism/*toxicity ; Copper-Transporting ATPases/genetics/metabolism ; Disease Models, Animal ; Humans ; Neurodegenerative Diseases/*drug therapy/genetics/metabolism/pathology ; Oxidative Stress/drug effects ; Superoxide Dismutase-1/genetics/metabolism ; }, abstract = {Copper is an essential trace element for the human body since it is a cofactor of several enzymes and proteins and plays a pivotal role in several biological functions (e.g., respiration, protection from oxidative damage, iron metabolism, etc.), also including the central nervous system development and functioning (e.g., synthesis of neurotransmitters, myelination, activation of neuropeptides, etc.). Therefore, copper dysmetabolism is associated with different toxic effects, mainly represented by oxidative stress, and it has been reported in many neurodegenerative disorders, such as Wilson's disease, Menkes disease, Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. This paper shows a detailed report of how copper is involved in the pathophysiology of these diseases. Moreover, a hint on novel therapeutic approaches based on restoring copper homeostasis through metal chelators will be pointed out.}, } @article {pmid29322690, year = {2018}, author = {Sánchez-España, J and Wang, K and Falagán, C and Yusta, I and Burgos, WD}, title = {Microbially mediated aluminosilicate formation in acidic anaerobic environments: A cell-scale chemical perspective.}, journal = {Geobiology}, volume = {16}, number = {1}, pages = {88-103}, doi = {10.1111/gbi.12269}, pmid = {29322690}, issn = {1472-4669}, mesh = {Aluminum Silicates/chemistry/*metabolism ; Anaerobiosis ; *Chemical Precipitation ; Ferrous Compounds/chemistry ; Hydrogen-Ion Concentration ; Microbiota ; Microscopy, Electron, Scanning Transmission ; Solubility ; Sulfates/chemistry ; *Water Microbiology ; }, abstract = {Through the use of scanning transmission electron microscopy (STEM) combined with other complementary techniques (SEM, cryo-TEM, HRTEM, and EELS), we have studied the interaction of microorganisms inhabiting deep anoxic waters of acidic pit lakes with dissolved aluminum, silica, sulfate, and ferrous iron. These elements were close to saturation (Al, SiO2) or present at very high concentrations (0.12 m Fe(II), 0.12-0.22 m SO4[2-]) in the studied systems. The anaerobic conditions of these environments allowed investigation of geomicrobial interactions that are difficult to see in oxidized, Fe(III)-rich environments. Detailed chemical maps and through-cell line scans suggest both extra- and intracellular accumulation of Al, Si, S, and Fe(II) in rod-like cells and other structures (e.g., spherical particles and bacteriomorphs) of probable microbial origin. The bacterial rods showed external nanometric coatings of adsorbed Fe(II) and Al on the cell surface and cell interiors with significant presence of Al, Si, and S. These microbial cells coexist with spherical particles showing similar configuration (Fe(II) external coatings and [Al, Si, S]-rich cores). The Al:Si and Al:S ratios and the good Al-Si correlation in the cell interiors suggest the concurrent formation of two amorphous phases, namely a proto-aluminosilicate with imogolite-like composition and proto-hydrobasaluminite. In both cases, the mineralization appears to comprise two stages: a first stage of aluminosilicate and Al-hydroxysulfate precipitation within the cell or around cellular exudates, and a second stage of SO4[2-] and Fe(II) adsorption on surface sites existing on the mineral phases in the case of (SO4[2-]) or on presumed organic molecules [in the case of Fe(II)]. These microbially related solids could have been formed by permineralization and mineral replacement of senescent microbial cells. However, these features could also denote biomineralization by active bacterial cells as a detoxification mechanism, a possibility which should be further explored. We discuss the significance of the observed Al/microbe and Si/microbe interactions and the implications for clay mineral formation at low pH.}, } @article {pmid29310023, year = {2018}, author = {Quaremba, G and Buccelli, C and Graziano, V and Laino, A and Laino, L and Paternoster, M and Petrone, P}, title = {Some inconsistencies in Demirjian's method.}, journal = {Forensic science international}, volume = {283}, number = {}, pages = {190-199}, doi = {10.1016/j.forsciint.2017.12.027}, pmid = {29310023}, issn = {1872-6283}, mesh = {Adolescent ; Age Determination by Teeth/*methods ; *Algorithms ; Child ; Humans ; *Models, Statistical ; Tooth/growth & development ; Tooth Apex/growth & development ; Tooth Calcification ; }, abstract = {Nowadays, given the massive migration movements toward and across EU countries, age assessment can be highly useful for estimating the real age of asylum seekers or in medico-legal assessments of age-disputed children charged with criminal acts. Demirjian et al.'s dental maturity score is currently a dental scoring system universally adopted for age assessment of unidentified children. Here we explore the biological compatibility of Demirjian's scores with respect to the estimation of certain chronological ages of forensic interest through an algorithm based on the theory of constrained graphs integrated with combinatory analysis. Rather than simply respect Demirjian's indications (direct method) on a sample of children, we followed a reverse procedure (indirect method) as follows: i. chronological age selection and identification of the corresponding maturity score (MS); ii. determination of all the possible combinations of dental maturity stages whose sum of the scores is equal to the MS under consideration; iii. checking for all such possible combinations the biological congruity of the state of maturity of each tooth compared to the chronological age initially chosen. By evidencing dental development inconsistencies, our mathematical approach explains why Demirjian's method typically overestimates age. Therefore, even if the method in question remains the recommended way to assess individual dental maturity, it should definitely be considered unsuitable for application in certain forensic scenarios, particularly as regards the most disputed age range 14-16 years.}, } @article {pmid29305223, year = {2018}, author = {Lemoine, S and Jost, D and Briche, F and Tourtier, JP}, title = {Re: Cox et al.'s article "Liver lacerations as a complication of CPR during pregnancy." Chest compressions performed on peripartum patients with a mechanical chest device: Experience of prehospital teams in the Paris area.}, journal = {Resuscitation}, volume = {127}, number = {}, pages = {e3-e4}, doi = {10.1016/j.resuscitation.2017.12.032}, pmid = {29305223}, issn = {1873-1570}, mesh = {Cardiopulmonary Resuscitation ; Female ; Humans ; *Lacerations ; Liver ; Paris ; *Peripartum Period ; Pregnancy ; }, } @article {pmid29305155, year = {2018}, author = {Wassiliwizky, E}, title = {At the root of the paradox: Comment on "An integrative review of the enjoyment of sadness associated with music" by Tuomas Eerola et al.}, journal = {Physics of life reviews}, volume = {25}, number = {}, pages = {136-138}, doi = {10.1016/j.plrev.2017.12.008}, pmid = {29305155}, issn = {1873-1457}, mesh = {*Auditory Perception ; Grief ; *Music ; Pleasure ; }, abstract = {Eerola et al.'s multi-layered model for the pleasure taken in music-elicited sadness is an important step in integrating explanatory accounts from different disciplines. Here, I would like to point out two theoretical inconsistencies that lie at the very root of the paradox and can have a major impact on future studies: first, the conflation of the transformation hypothesis and the co-activation hypothesis of sadness and pleasure, and second, the conflation of sadness that is elicited by musical instruments and that which is elicited by lyrics.}, } @article {pmid29297578, year = {2017}, author = {Lucavei, J and Pougnet, L and Dewitte, JD and Loddé, B and Pougnet, R}, title = {Comments to Nordmo et al.'s article: effect of hardiness.}, journal = {International maritime health}, volume = {68}, number = {4}, pages = {260-261}, doi = {10.5603/IMH.2017.0045}, pmid = {29297578}, issn = {2081-3252}, mesh = {Humans ; *Military Personnel ; Norway ; *Sleep ; }, abstract = {We would like to comment on Nordmo et al.'s article on hardiness among Norwegian Royal Navy seamen. The article is very interesting. Understanding the sleep disorders of the military can indeed make it possible to favour the preservation of their health and their competencies. The authors have highlighted the limitations of their study. They will take into account the sleep disorder factors already described in literature, such as: noise, comfort on board, shift organisations, etc. We would like to make two comments: on the one hand, highlight another limit to help future studies; on the other hand, open another perspective of prevention, not described in this article.}, } @article {pmid29293263, year = {2018}, author = {Geoffrey White, K}, title = {Direct remembering, mediated remembering, and atypical forgetting functions.}, journal = {Journal of the experimental analysis of behavior}, volume = {109}, number = {1}, pages = {70-86}, doi = {10.1002/jeab.298}, pmid = {29293263}, issn = {1938-3711}, mesh = {Animals ; Columbidae ; Conditioning, Operant ; Humans ; *Memory ; Memory, Short-Term ; *Mental Recall ; Psychological Theory ; Reinforcement Schedule ; Reinforcement, Psychology ; *Retention, Psychology ; }, abstract = {Atypical forgetting functions have been demonstrated in several recent studies of delayed matching to sample, in which experimental conditions are altered partway through the retention interval. The forgetting functions are atypical in that accuracy or discriminability is not always a negatively accelerated monotonic function of increasing retention interval duration, but may increase at later times in the retention interval. Atypical forgetting functions reflect changes in levels of discrimination. A switch from a lower level to a higher level of discrimination, or vice versa, can occur at any time in the retention interval. The behavioral theories of remembering proposed by Nevin, Davison, Odum, and Shahan (2007), and White and Brown (2014), offer quantitative predictions of forgetting functions that differ in intercept or slope. Both theories are able to account for atypical forgetting functions, by assuming time-independent changes in the mediating effect of attending to sample and comparison stimuli (in Nevin et al.'s model) or in the direct effect of the context of reinforcement of the conditional discrimination (in White & Brown's model). Despite differences in their main assumptions, the theories have an edge over any theory that assumes that forgetting is time-dependent.}, } @article {pmid31131375, year = {2018}, author = {De Sa, C and Gu, A and Ré, C and Sala, F}, title = {Representation Tradeoffs for Hyperbolic Embeddings.}, journal = {Proceedings of machine learning research}, volume = {80}, number = {}, pages = {4460-4469}, pmid = {31131375}, issn = {2640-3498}, support = {U54 EB020405/EB/NIBIB NIH HHS/United States ; }, abstract = {Hyperbolic embeddings offer excellent quality with few dimensions when embedding hierarchical data structures like synonym or type hierarchies. Given a tree, we give a combinatorial construction that embeds the tree in hyperbolic space with arbitrarily low distortion without using optimization. On WordNet, our combinatorial embedding obtains a mean-average-precision of 0.989 with only two dimensions, while Nickel et al.'s recent construction obtains 0.87 using 200 dimensions. We provide upper and lower bounds that allow us to characterize the precision-dimensionality tradeoff inherent in any hyperbolic embedding. To embed general metric spaces, we propose a hyperbolic generalization of multidimensional scaling (h-MDS). We show how to perform exact recovery of hyperbolic points from distances, provide a perturbation analysis, and give a recovery result that allows us to reduce dimensionality. The h-MDS approach offers consistently low distortion even with few dimensions across several datasets. Finally, we extract lessons from the algorithms and theory above to design a PyTorch-based implementation that can handle incomplete information and is scalable.}, } @article {pmid31064502, year = {2018}, author = {Egloff, B}, title = {To make innovations such as replication mainstream, publish them in mainstream journals.}, journal = {The Behavioral and brain sciences}, volume = {41}, number = {}, pages = {e126}, doi = {10.1017/S0140525X18000614}, pmid = {31064502}, issn = {1469-1825}, mesh = {*Periodicals as Topic ; *Social Media ; }, abstract = {It was a pleasure to read Zwaan et al.'s wise and balanced target article. Here, I use it as a shining example for bolstering the argument that to make innovations such as replication mainstream, it seems advisable to move the debates from social media to respected "mainstream" psychology journals. Only then will mainstream psychologists be reached and, we hope, convinced.}, } @article {pmid29279738, year = {2017}, author = {Srivastava, A and Nanda, G and Mahajan, R and Nanda, A and Mishra, N and Karmaran, S and Batra, S and Chhabra, HS}, title = {Computed Tomography-Based Occipital Condyle Morphometry in an Indian Population to Assess the Feasibility of Condylar Screws for Occipitocervical Fusion.}, journal = {Asian spine journal}, volume = {11}, number = {6}, pages = {847-853}, pmid = {29279738}, issn = {1976-1902}, abstract = {STUDY DESIGN: A retrospective computed tomography (CT)-based morphometric study of 82 occipital condyles in the Indian population, focusing on critical morphometric dimensions with relation to placing condylar screws.

PURPOSE: This study focused on determining the feasibility of placing occipital condylar screws in an Indian population using CT anatomical morphometric data.

OVERVIEW OF LITERATURE: The occipital condylar screw is a novel technique being explored as one of the options in occipitocervical stabilization. Sex and ethnic variations in anatomical structures may restrict the feasibility of this technique in some populations. To the best of our knowledge, there are no CT-based data on an Indian population that assess the feasibility of occipital condylar screws.

METHODS: We measured the dimensions of 82 occipital condyles in 41 adults on coronal, sagittal, and axial reconstructed CT images. The differences were noted between the right and left sides and also between males and females. Statistical analysis was performed using the t-test, with a p-value of <0.05 considered significant.

RESULTS: Mean sagittal length and height were 17.2±1.7 mm and 9.1±1.5 mm, respectively. Mean condylar angle/screw angle was 38.0°±5.5° from midline, with mean condylar length and width of 19.6±2.6 mm and 9.5±1.0 mm, respectively. Average coronal height on the anterior and posterior hypoglossal canal was 10.8±1.4 mm and 9.0±1.4 mm, respectively. The values in females were significantly lower than those in males, except for screw angle and condylar width. Based on Lin et al.'s proposed criteria, eight of 82 condyles were not suitable for condylar screws.

CONCLUSIONS: Preliminary CT morphometry data of the occipital condyle shows that condylar screws are anatomically feasible in a large portion of the Indian population. However, because a small number of population may not be suitable for this technique, meticulous study of preoperative anatomy using detailed CT data is advised.}, } @article {pmid29267423, year = {2017}, author = {Bordeleau, L and Leblanc, J}, title = {[Interprofessional Collaboration as a Modality to Resolve Therapeutic Impasses in Child Psychiatry: A Review].}, journal = {Sante mentale au Quebec}, volume = {42}, number = {2}, pages = {229-243}, pmid = {29267423}, issn = {0383-6320}, mesh = {Child ; Child Psychiatry ; Humans ; Mental Disorders/*therapy ; Mental Health Services ; Models, Organizational ; *Patient Care Team/organization & administration ; }, abstract = {Child and adolescent intervention in child psychiatric clinics generates a high risk of therapeutic impasses for clinicians. Among the factors that contribute to this situation are the increasing severity of the problems of young people who are referred to psychiatric clinics and the obligation for professionals to collaborate with various actors surrounding the patient. This literature review explores the possibility that an intervention targeting indicators of interprofessional collaboration can help resolved the therapeutic impasses encountered by professionals working in child psychiatry. The article begins with a description of the impasse in therapeutic clinical child psychiatry. It then introduces a broad look at research about interprofessional collaboration and its effects on mental health service delivery. Finally, it examines the structuring model of the interprofessional collaboration process of D'Amour et al. in order to highlight the indicators that may be related to the resolution of clinical therapeutic impasses in child psychiatry. This review examines the possible interventions that could be done when targeting indicators of D'Amour et al.'s interprofessional collaboration model in order to improve therapeutic impasses resolution. A promising direction for future research which could contribute to therapeutic impasses resolution in child psychiatry is proposed.}, } @article {pmid29265831, year = {2018}, author = {Farb, N and Anderson, A and Ravindran, A and Hawley, L and Irving, J and Mancuso, E and Gulamani, T and Williams, G and Ferguson, A and Segal, ZV}, title = {Prevention of relapse/recurrence in major depressive disorder with either mindfulness-based cognitive therapy or cognitive therapy.}, journal = {Journal of consulting and clinical psychology}, volume = {86}, number = {2}, pages = {200-204}, doi = {10.1037/ccp0000266}, pmid = {29265831}, issn = {1939-2117}, support = {//Canadian Institute of Health Research/International ; }, mesh = {Adult ; Antidepressive Agents/therapeutic use ; Cognitive Behavioral Therapy/*methods ; Depressive Disorder, Major/*therapy ; Female ; Humans ; Male ; Middle Aged ; Mindfulness/*methods ; *Outcome Assessment, Health Care ; Recurrence ; Secondary Prevention/*methods ; }, abstract = {OBJECTIVE: Both Mindfulness Based Cognitive Therapy (MBCT) and Cognitive Therapy (CT) enhance self-management of prodromal symptoms associated with depressive relapse, albeit through divergent therapeutic procedures. We evaluated rates of relapse in remitted depressed patients receiving MBCT and CT. Decentering and dysfunctional attitudes were assessed as treatment-specific process markers.

METHOD: Participants in remission from Major Depressive Disorder (MDD; N = 166) were randomized to 8 weeks of either MBCT (N = 82) or CT (N = 84) and were followed for 24 months, with process markers measured every 3 months. Attendance in both treatments was high (6.3/8 session) and treatment fidelity and competence were evaluated. Relapse was defined as a return of symptoms meeting the criteria for major depression on Module A of the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders (SCID).

RESULTS: Intention-to-treat analyses indicated no differences between MBCT and CT in either rates of relapse to MDD or time to relapse across 24 months of follow up. Both groups experienced significant increases in decentering and participants in CT reported greater reductions in dysfunctional attitudes. Within both treatments, participants who relapsed evidenced lower decentering scores than those who stayed well over the follow up.

CONCLUSIONS: This is the first study to directly compare relapse prophylaxis following MBCT and CT directly. The lack of group differences in time to relapse supports the view that both interventions are equally effective and that increases in decentering achieved via either treatment are associated with greater protection. These findings lend credence to Teasdale et al.'s (2002) contention that, even though they may be taught through dissimilar methods, CT and MBCT help participants develop similar metacognitive skills for the regulation of distressing thoughts and emotions. (PsycINFO Database Record}, } @article {pmid29261033, year = {2018}, author = {Lemon, C and Liu, N and Lane, S and Sud, A and Branley, J and Khadra, M and Kim, J}, title = {Changes in User Perceptions of a Telemedicine System Over Time: From Initial Implementation to Everyday Use.}, journal = {Telemedicine journal and e-health : the official journal of the American Telemedicine Association}, volume = {24}, number = {7}, pages = {552-559}, doi = {10.1089/tmj.2017.0194}, pmid = {29261033}, issn = {1556-3669}, mesh = {Adult ; *Attitude of Health Personnel ; *Attitude to Computers ; *Computers, Handheld ; Humans ; *Mobile Applications ; Nurses/*psychology ; Program Development ; Program Evaluation ; Surveys and Questionnaires ; Telemedicine/*instrumentation ; Time Factors ; User-Computer Interface ; }, abstract = {BACKGROUND: Benefits associated with telemedicine are contingent upon positive user perceptions. Despite this, research on user perceptions of telemedicine remains limited.

INTRODUCTION: Usability approaches offer a robust way to assess user perceptions, but have rarely been applied in telemedicine. In this study, a usability approach was employed to examine how user perceptions toward a telemedicine system changed over the course of everyday use.

MATERIALS AND METHODS: A telemedicine system was introduced to a hospital in the home service. Ten mobile nurses completed the System Usability Scale (SUS) after initial use, then again after 18 months of everyday use. Results were compared. Analysis included Bangor et al.'s (2009) adjective rating scale.

RESULTS: The initial SUS mean was 83 (standard deviation [SD] = 7.98), indicating "excellent" usability. After 18 months, the SUS mean was 64.38, indicating "OK" usability (SD = 14.25, p < 0.05, 95% confidence interval [CI]). Over time, users had lower desire to use the system frequently (p < 0.05, 95% CI), found it more complex (p < 0.05, 95% CI), and perceived greater inconsistency in its design (p < 0.05, 95% CI).

DISCUSSION: Considered with existing evidence, our usability findings indicate that a temporary period of positive user perceptions occurs when new telemedicine systems are used for the first few months. This fades with everyday use, with design inconsistency and perceived complexity becoming more noticeable. Although other factors such as user satisfaction and efficiency may also contribute, further studies are needed for confirmation.

CONCLUSIONS: User perceptions of telemedicine vary with time. To help maximize the benefits and longevity of telemedicine systems, responding to intermittent user appraisal is desirable.}, } @article {pmid29250774, year = {2018}, author = {South Palomares, JK and Sutherland, CAM and Young, AW}, title = {Facial first impressions and partner preference models: Comparable or distinct underlying structures?.}, journal = {British journal of psychology (London, England : 1953)}, volume = {109}, number = {3}, pages = {538-563}, doi = {10.1111/bjop.12286}, pmid = {29250774}, issn = {2044-8295}, mesh = {*Choice Behavior ; Cognition ; *Face/anatomy & histology ; Facial Expression ; Female ; Humans ; *Judgment ; Male ; *Models, Psychological ; *Personality ; Sexual Partners/*psychology ; Young Adult ; }, abstract = {Given the frequency of relationships nowadays initiated online, where impressions from face photographs may influence relationship initiation, it is important to understand how facial first impressions might be used in such contexts. We therefore examined the applicability of a leading model of verbally expressed partner preferences to impressions derived from real face images and investigated how the factor structure of first impressions based on potential partner preference-related traits might relate to a more general model of facial first impressions. Participants rated 1,000 everyday face photographs on 12 traits selected to represent (Fletcher, et al. 1999, Journal of Personality and Social Psychology, 76, 72) verbal model of partner preferences. Facial trait judgements showed an underlying structure that largely paralleled the tripartite structure of Fletcher et al.'s verbal preference model, regardless of either face gender or participant gender. Furthermore, there was close correspondence between the verbal partner preference model and a more general tripartite model of facial first impressions derived from a different literature (Sutherland et al., 2013, Cognition, 127, 105), suggesting an underlying correspondence between verbal conceptual models of romantic preferences and more general models of facial first impressions.}, } @article {pmid29248841, year = {2018}, author = {Alharbi, HA}, title = {Readiness for self-directed learning: How bridging and traditional nursing students differs?.}, journal = {Nurse education today}, volume = {61}, number = {}, pages = {231-234}, doi = {10.1016/j.nedt.2017.12.002}, pmid = {29248841}, issn = {1532-2793}, mesh = {Adult ; Education, Nursing, Baccalaureate/*methods ; Female ; Humans ; *Learning ; Male ; Models, Educational ; Saudi Arabia ; Students, Nursing/*psychology ; Surveys and Questionnaires ; }, abstract = {BACKGROUND: The dean of the nursing college has an initiative to reform the BSN program in the college to minimize the use of lecturing and maximize interactive and lifelong learning. Appropriate assessment of how our students are prepared to be self-directed learners is crucial.

OBJECTIVE: To compare traditional and bridging students in regard to their SDLR scores in the nursing college in Saudi Arabia.

DESIGN: This was a comparative study to compare traditional and bridging students in regard to their self-directed learning readiness scores (SDLR).

SETTINGS: The data was collected at the Nursing College, King Saud University, Riyadh, Saudi Arabia.

PARTICIPANTS: A convenient sample of undergraduate nursing students at the sixth and eighth levels in both regular and bridging programs were recruited in this study to indicate their SDLR scores.

METHODS: The study used Fisher et al.'s (2001) Self-Directed Learning Readiness Scale to measure the self-directed learning readiness among undergraduate nursing students.

RESULTS: The total mean score of SDLR was 144 out of 200, which indicated a low level of readiness for SDL. There were significant variations between the included academic levels among participants. Students in the sixth academic level scored higher in the total SDLR scores compared to eighth-level students. There were no significant variations with gender and program types in the total SDLR scores.

CONCLUSIONS: A comprehensive plan is needed to prepare both faculty members and students to improve the SDL skills.}, } @article {pmid29245636, year = {2017}, author = {Bush, B}, title = {Additions to the description of Paroplocephalus atriceps (Serpentes: Elapidae) with a discussion on pupil shape in it and other Australian snakes.}, journal = {Zootaxa}, volume = {4344}, number = {2}, pages = {333-344}, doi = {10.11646/zootaxa.4344.2.8}, pmid = {29245636}, issn = {1175-5334}, mesh = {Animals ; Australia ; Elapid Venoms ; *Elapidae ; Snakes ; }, abstract = {Morphometric data on an additional twelve individuals of Paroplocephalus atriceps Storr are included enlarging Keogh et al.'s 2000 description of the genus and further verifying its affinities with Hoplocephalus. Included are comments on its venom and observations confirming arboreality and although primarily nocturnal, it includes some diurnal activity. Various authors have erroneously suggested it has vertically elliptic pupils but they are round. During an examination of snake's eyes, it was found that several additional species have pupils that require re-describing, especially Suta fasciata Rosen, S. punctata Boulenger and Echiopsis curta Schlegel, all of which include individuals with round pupils. A standardised description is suggested for each of the three common pupil shapes in snakes as narrow elliptic where dilation and constriction is lateral or vertical only, wide elliptic where dilation and constriction is both lateral and vertical, and round where any dilation and constriction is equidistant from the centre around the pupil's circumference.}, } @article {pmid29245495, year = {2017}, author = {Stiles, FG and Remsen, JVJ and McGuire, JA}, title = {The generic classification of the Trochilini (Aves: Trochilidae): Reconciling taxonomy with phylogeny.}, journal = {Zootaxa}, volume = {4353}, number = {3}, pages = {401-424}, doi = {10.11646/zootaxa.4353.3.1}, pmid = {29245495}, issn = {1175-5334}, mesh = {Animals ; *Birds ; Phylogeny ; }, abstract = {The generic nomenclature of the hummingbirds is unusually complicated. McGuire et al.'s (2014) recent phylogeny of the Trochilidae based on DNA sequence data has greatly clarified relationships within the family but conflicts strongly with the traditional classification of the family at the genus level, especially that of the largest and most recently derived clade, the Trochilini or "emeralds". We recently presented a historical review of this classification and the generic modifications required by the Code of the International Commission on Zoological Nomenclature. Herein we present a revised generic classification of the Trochilini based upon McGuire et al.'s genetic data, while producing diagnosable generic groupings and preserving nomenclatural stability insofar as possible. However, this generic rearrangement has necessitated the resurrection of nine generic names currently considered synonyms, the synonymization of seven currently recognized genera and the creation of one new genus. The generic changes we recommend to the classification are drastic, and we summarize these in tabular form in comparison with the three most recent classifications of the Trochilini. Where appropriate, we outline alternatives to our proposed arrangement. The classification treats 110 species in 35 genera, including two species that remain unplaced for lack of genetic samples.}, } @article {pmid29239651, year = {2017}, author = {Chuderski, A and Jastrzębski, J}, title = {Working memory facilitates insight instead of hindering it: Comment on DeCaro, Van Stockum, and Wieth (2016).}, journal = {Journal of experimental psychology. Learning, memory, and cognition}, volume = {43}, number = {12}, pages = {1993-2004}, doi = {10.1037/xlm0000409}, pmid = {29239651}, issn = {1939-1285}, support = {//National Science Centre of Poland/ ; }, abstract = {The "nothing-special" account of insight predicts positive correlations of insight problem solving and working memory capacity (WMC), whereas the "special-process" account expects no, or even negative, correlations. In the latter vein, DeCaro, Van Stockum Jr., and Wieth (2016) have recently reported weak negative WMC correlations with 2 constraint relaxation matchstick problems and 3 insight problems, and thus they claim that WM hinders insight. Here, we report on 3 studies that investigated WMC and various matchstick and classical problems (including 1 study that precisely replicated DeCaro et al.'s procedure). All 3 studies yielded moderate positive correlations of WMC with both the constraint relaxation and the classical problems. WMC explained 10% variance in problem solving, no matter what problems were used or how they were applied. Thus, DeCaro et al.'s claim that WM hinders insight is unwarranted. The opposite is true: WM facilitates insight. (PsycINFO Database Record}, } @article {pmid29214474, year = {2018}, author = {Biegler, R}, title = {Insufficient evidence for habituation in Mimosa pudica. Response to Gagliano et al. (2014).}, journal = {Oecologia}, volume = {186}, number = {1}, pages = {33-35}, pmid = {29214474}, issn = {1432-1939}, mesh = {*Mimosa ; }, abstract = {Gagliano et al. (Oecologia 175(1):63-72, 2014) reported that Mimosa pudica habituates to repeated stimulation, as shown by a reduction in response, dishabituation, and stimulus specificity. I argue that Gagliano et al.'s data show an absence of dishabituation, that their experimental design needs an additional condition to test whether there is stimulus specificity, and that most of their data can be explained by motor fatigue. Some data are not easily explained by fatigue, and I suggest a further analysis that may clarify the issue. The status of habituation in Mimosa remains uncertain.}, } @article {pmid29205103, year = {2019}, author = {Lu, J}, title = {Sharpening randomization-based causal inference for 2[2] factorial designs with binary outcomes.}, journal = {Statistical methods in medical research}, volume = {28}, number = {4}, pages = {1064-1078}, doi = {10.1177/0962280217745720}, pmid = {29205103}, issn = {1477-0334}, mesh = {Biomedical Research/statistics & numerical data ; Factor Analysis, Statistical ; Models, Statistical ; *Random Allocation ; *Research Design/statistics & numerical data ; }, abstract = {In medical research, a scenario often entertained is randomized controlled 2[2] factorial design with a binary outcome. By utilizing the concept of potential outcomes, Dasgupta et al. proposed a randomization-based causal inference framework, allowing flexible and simultaneous estimations and inferences of the factorial effects. However, a fundamental challenge that Dasgupta et al.'s proposed methodology faces is that the sampling variance of the randomization-based factorial effect estimator is unidentifiable, rendering the corresponding classic "Neymanian" variance estimator suffering from over-estimation. To address this issue, for randomized controlled 2[2] factorial designs with binary outcomes, we derive the sharp lower bound of the sampling variance of the factorial effect estimator, which leads to a new variance estimator that sharpens the finite-population Neymanian causal inference. We demonstrate the advantages of the new variance estimator through a series of simulation studies, and apply our newly proposed methodology to two real-life datasets from randomized clinical trials, where we gain new insights.}, } @article {pmid29194239, year = {2017}, author = {Durkin, AE and Feinn, RS}, title = {Traditional and Accelerated Baccalaureate Nursing Students' Self-Efficacy for Interprofessional Learning.}, journal = {Nursing education perspectives}, volume = {38}, number = {1}, pages = {23-28}, doi = {10.1097/01.NEP.0000000000000101}, pmid = {29194239}, issn = {1536-5026}, mesh = {Adult ; Clinical Competence ; Cooperative Behavior ; Curriculum ; Education, Nursing, Baccalaureate/*methods ; Female ; Humans ; *Interprofessional Relations ; Male ; Nursing Education Research ; *Problem-Based Learning ; *Self Efficacy ; Surveys and Questionnaires ; }, abstract = {AIM: The aim of the study was to examine self-efficacy among traditional and accelerated nursing students with regard to interprofessional learning.

BACKGROUND: The World Health Organization and other organizations recognize the need for interprofessional education to prepare health care providers for collaborative practice. Graduates of baccalaureate nursing programs require competence in interprofessional collaboration and communication.

METHOD: Traditional (n = 239) and accelerated (n = 114) nursing students' self-efficacy was measured utilizing Mann et al.'s Self-Efficacy for Interprofessional Experiential Learning Scale.

RESULTS: Accelerated students averaged significantly higher than traditional students on the interprofessional team evaluation and feedback subscale (p = .006) and overall self-efficacy (p = .041).

CONCLUSION: Awareness of possible differences between traditional and accelerated nursing students with regard to self-efficacy may help faculty develop effective interprofessional learning experiences for students in each cohort. Although results cannot be generalized, findings from this study provide evidence to guide the selection of learning strategies.}, } @article {pmid30931421, year = {2017}, author = {Gibson, E and Jara-Ettinger, J and Levy, R and Piantadosi, S}, title = {The Use of a Computer Display Exaggerates the Connection Between Education and Approximate Number Ability in Remote Populations.}, journal = {Open mind : discoveries in cognitive science}, volume = {1}, number = {3}, pages = {159-168}, pmid = {30931421}, issn = {2470-2986}, abstract = {Piazza et al. reported a strong correlation between education and approximate number sense (ANS) acuity in a remote Amazonian population, suggesting that symbolic and nonsymbolic numerical thinking mutually enhance one another over in mathematics instruction. But Piazza et al. ran their task using a computer display, which may have exaggerated the connection between the two tasks, because participants with greater education (and hence better exact numerical abilities) may have been more comfortable with the task. To explore this possibility, we ran an ANS task in a remote population using two presentation methods: (a) a computer interface and (b) physical cards, within participants. If we only analyze the effect of education on ANS as measured by the computer version of the task, we replicate Piazza et al.'s finding. But importantly, the effect of education on the card version of the task is not significant, suggesting that the use of a computer display exaggerates effects. These results highlight the importance of task considerations when working with nonindustrialized cultures, especially those with low education. Furthermore, these results raise doubts about the proposal advanced by Piazza et al. that education enhances the acuity of the approximate number sense.}, } @article {pmid29183418, year = {2018}, author = {Cristea, IA and Naudet, F}, title = {Defending psychiatry or defending the trivial effects of therapeutic interventions? A citation content analysis of an influential paper.}, journal = {Epidemiology and psychiatric sciences}, volume = {27}, number = {3}, pages = {230-239}, pmid = {29183418}, issn = {2045-7960}, mesh = {*Bibliometrics ; Humans ; Mental Disorders/*drug therapy ; Periodicals as Topic/*statistics & numerical data ; Pharmaceutical Preparations ; Psychiatry/*statistics & numerical data ; Psychotropic Drugs/*therapeutic use ; }, abstract = {AIMS: Leucht et al. in 2012 described an overview of meta-analyses of the efficacy of medication in psychiatry and general medicine, concluding that psychiatric drugs were not less efficacious than other drugs. Our goal was to explore the dissemination of this highly cited paper, which combined a thought provoking message with a series of caveats.

METHODS: We conducted a prospectively registered citation content analysis. All papers published before June 1st citing the target paper were independently rated by two investigators. The primary outcome coded dichotomously was whether the citation was used to justify a small or modest effect observed for a given treatment. Secondary outcomes regarded mentioning any caveats when citing the target paper, the point the citation was making (treatment effectiveness in psychiatry closely resembles that in general medicine, others), the type of condition (psychiatric, medical or both), specific disease, treatment category and specific type. We also extracted information about the type of citing paper, financial conflict of interest (COI) declared and any industry support. The primary analysis was descriptive by tabulating the extracted variables, with numbers and percentages where appropriate. Co-authorship networks were constructed to identify possible clusters of citing authors. An exploratory univariate logistic regression was used to explore the relationship between each of a subset of pre-specified secondary outcomes and the primary outcome.

RESULTS: We identified 135 records and retrieved and analysed 120. Sixty-three (53%) quoted Leucht et al.'s paper to justify a small or modest effect observed for a given therapy, and 113 (94%) did not mention any caveats. Seventy-two (60%) used the citation to claim that treatment effectiveness in psychiatry closely resembles that in general medicine; 110 (91%) paper were about psychiatric conditions. Forty-one (34%) papers quoted it without pointing towards any specific treatment category, 28 (23%) were about antidepressants, 18 (15%) about antipsychotics. Forty (33%) of the citing papers included data. COIs were reported in 55 papers (46%). Univariate and multivariate regressions showed an association between a quote justifying small or modest effects and the point that treatment effectiveness in psychiatry closely resembles that in general medicine.

CONCLUSIONS: Our evaluation revealed an overwhelmingly uncritical reception and seemed to indicate that beyond defending psychiatry as a discipline, the paper by Leucht et al. served to lend support and credibility to a therapeutic myth: trivial effects of mental health interventions, most often drugs, are to be expected and therefore accepted.Protocol registration: https://osf.io/9dqat/.}, } @article {pmid29179626, year = {2018}, author = {Dubé, K and Sylla, L and Dee, L}, title = {Reply to Commentary: "Are HIV-Infected Candidates for Participation in Risky Cure-Related Studies Otherwise Healthy?".}, journal = {Journal of empirical research on human research ethics : JERHRE}, volume = {13}, number = {1}, pages = {23-25}, doi = {10.1177/1556264617741715}, pmid = {29179626}, issn = {1556-2654}, mesh = {HIV Infections ; Healthy Volunteers ; Humans ; *Research Design ; *Risk Assessment ; }, abstract = {We respond to Eyal et al.'s commentary focusing on how people living with HIV participating in HIV cure-related studies are defined. We argue that the types of participants enrolled in research cannot be dissociated from the study interventions, the types of anticipated risks, and the background standard of care. As the field of HIV cure research advances, more nuance and granularity will be needed to define research criteria and acceptable risk/benefit ratios for cure study participants, as well as specific tiered protocol designs that serve to protect various participant populations from untoward risks, especially in very early phase research with interventions known to have potentially serious toxicities. We highlight key lessons from the ACTIVATE study involving a latency-reversing agent, Panobinostat, for HIV cure study design involving "otherwise healthy volunteers".}, } @article {pmid29177816, year = {2018}, author = {Blackwell, SE}, title = {Frames of Reference and Antecedentless Anaphora in Spanish Conversation.}, journal = {Journal of psycholinguistic research}, volume = {47}, number = {2}, pages = {283-305}, pmid = {29177816}, issn = {1573-6555}, mesh = {Cognition ; *Communication ; Humans ; *Language ; *Psycholinguistics ; Spain ; }, abstract = {This study examines native Spanish speakers' use of anaphoric pronouns and null subjects in conversational discourse in the absence of coreferential antecedents. It also considers the adequacy of Gundel et al.'s proposal (Language 69(2):274-307, 1993) that the cognitive status "in focus" corresponds with speakers' use of minimal referring expressions (i.e., unstressed pronouns and zeros). Analysis of naturally occurring Spanish conversation shows how the felicitous use and interpretation of non-canonical (antecedentless) anaphoric pronouns and null subjects are possible due to the activation of underlying cognitive frames that are shared by the interlocutors. Furthermore, the speaker's mention of a referent, dubbed a "neighborhood antecedent" by Langacker (Conceptual grouping and pronominal anaphora, in: Fox (ed) Studies in anaphora, Cambridge University Press, Cambridge, 1996), and the information "filled in" over the course of the conversation on account of the activation of relevant cognitive frames, both license and disambiguate the non-canonical anaphoric relations.}, } @article {pmid29172911, year = {2018}, author = {Hilkert, SM and Parness-Yossifon, R and Mets-Halgrimson, R and Mets, MB}, title = {Response to Galvis et al.'s "Myopia rates in a genetically isolated population".}, journal = {Ophthalmic genetics}, volume = {39}, number = {2}, pages = {295}, doi = {10.1080/13816810.2017.1403724}, pmid = {29172911}, issn = {1744-5094}, mesh = {Humans ; *Myopia ; }, } @article {pmid29169266, year = {2017}, author = {Cyganik, Ł and Binkowski, M and Kokot, G and Cyganik, P and Rusin, T and Bolechała, F and Nowak, R and Wróbel, Z and John, A}, title = {Microscale's relationship between Young's modulus and tissue density. Prediction of displacements.}, journal = {Computer methods in biomechanics and biomedical engineering}, volume = {20}, number = {16}, pages = {1658-1668}, doi = {10.1080/10255842.2017.1404993}, pmid = {29169266}, issn = {1476-8259}, mesh = {*Bone Density ; *Elastic Modulus ; Femur Head/physiology ; Finite Element Analysis ; Humans ; Models, Theoretical ; Numerical Analysis, Computer-Assisted ; X-Ray Microtomography ; }, abstract = {The study presents an experimental verification of Wagner et al.'s relationship in microscale and proposes a modification of this relationship. For this purpose, 11 cubic specimens were microcomputed tomography scanned and mechanically tested with the displacement full-field measurements using a digital image correlation system. Then, numerical simulations of the compression tests were performed using a finite elements method. The Young's modulus distributions assigned to the finite elements models were calculated using both of Wagner et al.'s relationships: original and modified. Comparison of the experimental and numerical results indicated the accuracy of numerical solutions for both relationships.}, } @article {pmid29148600, year = {2018}, author = {Martin, CH and Höhna, S}, title = {New evidence for the recent divergence of Devil's Hole pupfish and the plausibility of elevated mutation rates in endangered taxa.}, journal = {Molecular ecology}, volume = {27}, number = {4}, pages = {831-838}, doi = {10.1111/mec.14404}, pmid = {29148600}, issn = {1365-294X}, support = {S10 RR029668/RR/NCRR NIH HHS/United States ; S10 RR027303/RR/NCRR NIH HHS/United States ; }, mesh = {Animals ; Genomics ; Humans ; Killifishes ; *Mutation Rate ; *Phylogeny ; }, abstract = {Sağlam et al. recently argued that the Devil's Hole pupfish (Cyprinodon diabolis), a conservation icon with the smallest known species range, was isolated 60 kya based on a new genomic data set. If true, this would be a radically long timescale for any species to persist at population sizes <500 individuals, in contrast to conservation genetics theory. However, here we argue that their analyses and interpretation are inappropriate. They placed highly restrictive prior distributions on divergence times, which do not appropriately model the large uncertainty and result in removing nearly all uncertainty from their analyses, and chose among models by assuming that pupfishes exhibit human mutation rates. We reanalysed their data with their same methods, only using an informative prior for the plausible range of mutation rates observed across vertebrates, including an estimate of the genomewide mutation rate from a pedigree analysis of cichlid fishes. In fact, Saglam et al.'s phylogenetic data support much younger median divergence times for C. diabolis, ranging from 6.2 to 19.9 kya, overlapping with our previous phylogenetic divergence time estimates of 2.5-6.5 kya. There are many reasons to suspect an even younger age and higher mutation rate in C. diabolis, as we previously estimated, due to their high metabolism, small adult size, small population size and severe environmental stressors. In conclusion, our results highlight the need for measuring mutation rate in this fascinating species and suggest that the ages of endangered taxa present in small, isolated populations may frequently be overestimated.}, } @article {pmid29130248, year = {2017}, author = {Smetana, JG}, title = {COMMENTARY ON "MOVING THROUGH ADOLESCENCE: DEVELOPMENTAL TRAJECTORIES OF AFRICAN AMERICAN AND EUROPEAN AMERICAN YOUTH".}, journal = {Monographs of the Society for Research in Child Development}, volume = {82}, number = {4}, pages = {167-177}, doi = {10.1111/mono.12339}, pmid = {29130248}, issn = {1540-5834}, mesh = {Adolescent ; *Black or African American ; Humans ; United States ; }, abstract = {This commentary discusses Gutman et al.'s monograph on developmental trajectories of African American and European American youth. Conceptual and methodological strengths of the monograph are highlighted, and the historical context of the study, including societal and technological changes that have altered the experience of adolescence and advances in developmental science that have occurred since the MADICS was conducted, are discussed. Finally, several suggestions are offered for ways Gutman et al.'s analyses could be elaborated to address further questions about adolescent development in context.}, } @article {pmid29121536, year = {2017}, author = {Warburton, J and Winterton, R}, title = {A far greater sense of community: The impact of volunteer behaviour on the wellness of rural older Australians.}, journal = {Health & place}, volume = {48}, number = {}, pages = {132-138}, doi = {10.1016/j.healthplace.2017.10.005}, pmid = {29121536}, issn = {1873-2054}, mesh = {Adult ; Aged ; Aged, 80 and over ; *Aging ; Australia ; Community Participation/*psychology ; Female ; Health Behavior ; Humans ; Male ; Middle Aged ; *Qualitative Research ; Racial Groups ; *Rural Population ; Social Support ; Volunteers/*psychology ; }, abstract = {This paper builds on place-based research investigating the transformative potential of volunteering for service-deprived, ageing rural communities. Here, we critically explore the relationship between communities of place, voluntarism and wellness for rural older Australians. We draw on data from a large qualitative multi-site study, and utilise Ryan et al.'s (2005) systemic model of community attachment. Findings support the dual perspective of strong community sentiments through social embeddedness in rural communities; and personal interests, associated with rational choice theory, through healthy ageing practices. Both aspects have demonstrated positive impact on wellness, but also risks to wellness associated with over-expectations of volunteers.}, } @article {pmid29121050, year = {2017}, author = {Guo, H and Wang, P and Zhang, X and Huang, Y and Ma, F}, title = {A robust anonymous biometric-based authenticated key agreement scheme for multi-server environments.}, journal = {PloS one}, volume = {12}, number = {11}, pages = {e0187403}, pmid = {29121050}, issn = {1932-6203}, mesh = {Algorithms ; Biometric Identification/*methods ; Computer Security ; *Computers ; Logic ; }, abstract = {In order to improve the security in remote authentication systems, numerous biometric-based authentication schemes using smart cards have been proposed. Recently, Moon et al. presented an authentication scheme to remedy the flaws of Lu et al.'s scheme, and claimed that their improved protocol supports the required security properties. Unfortunately, we found that Moon et al.'s scheme still has weaknesses. In this paper, we show that Moon et al.'s scheme is vulnerable to insider attack, server spoofing attack, user impersonation attack and guessing attack. Furthermore, we propose a robust anonymous multi-server authentication scheme using public key encryption to remove the aforementioned problems. From the subsequent formal and informal security analysis, we demonstrate that our proposed scheme provides strong mutual authentication and satisfies the desirable security requirements. The functional and performance analysis shows that the improved scheme has the best secure functionality and is computational efficient.}, } @article {pmid29115940, year = {2017}, author = {Jiann, BP}, title = {Does hair dye use really increase the risk of prostate cancer?.}, journal = {BMC cancer}, volume = {17}, number = {1}, pages = {724}, pmid = {29115940}, issn = {1471-2407}, mesh = {Animals ; Case-Control Studies ; *Hair Dyes ; Humans ; Male ; Prognosis ; *Prostatic Neoplasms ; *Urinary Bladder Neoplasms ; }, abstract = {Recently, Shu-Yu Tai et al. reported that personal hair dye use increased risk of prostate cancer with a dose-response effect. Although hair dyes were identified as carcinogenic in animals and increased risk of some cancers among hairdressers, the existing epidemiological data did not support that personal hair dye use increased risk of cancers, even for bladder cancer. Given that Tai et al.'s report of a potential hazard of personal hair dye use on risk of prostate cancer was particular, the methodology of the study was scrutinized and some flaws were found including the issue of external validity.}, } @article {pmid29106282, year = {2017}, author = {Borsboom, D and Fried, EI and Epskamp, S and Waldorp, LJ and van Borkulo, CD and van der Maas, HLJ and Cramer, AOJ}, title = {False alarm? A comprehensive reanalysis of "Evidence that psychopathology symptom networks have limited replicability" by Forbes, Wright, Markon, and Krueger (2017).}, journal = {Journal of abnormal psychology}, volume = {126}, number = {7}, pages = {989-999}, doi = {10.1037/abn0000306}, pmid = {29106282}, issn = {1939-1846}, support = {//European Research Council/United States ; //Netherlands Organisation for Scientific Research/ ; }, mesh = {Antisocial Personality Disorder/complications/*psychology ; Anxiety Disorders/complications ; Data Interpretation, Statistical ; Depressive Disorder/complications ; Humans ; *Models, Psychological ; Reproducibility of Results ; }, abstract = {Forbes, Wright, Markon, and Krueger (2017) stated that "psychopathology networks have limited replicability" (p. 1011) and that "popular network analysis methods produce unreliable results" (p. 1011). These conclusions are based on an assessment of the replicability of four different network models for symptoms of major depression and generalized anxiety across two samples; in addition, Forbes et al. analyzed the stability of the network models within the samples using split-halves. Our reanalysis of the same data with the same methods led to results directly opposed to theirs: All network models replicated very well across the two data sets and across the split-halves. We trace the differences between Forbes et al.'s results and our own to the fact that they did not appear to accurately implement all network models and used debatable metrics to assess replicability. In particular, they deviated from existing estimation routines for relative importance networks, did not acknowledge the fact that the skip structure used in the interviews strongly distorted correlations between symptoms, and incorrectly assumed that network structures and metrics should be the same not only across the different samples but also across the different network models used. In addition to a comprehensive reanalysis of the data, we end with a discussion of best practices concerning future research into the replicability of psychometric networks. (PsycINFO Database Record}, } @article {pmid29103902, year = {2017}, author = {Lee, JH and Lee, C and Battulga, B and Na, JY and Hwang, JJ and Kim, YH and Han, SS}, title = {Morphological analysis of the lower second premolar for age estimation of Korean adults.}, journal = {Forensic science international}, volume = {281}, number = {}, pages = {186.e1-186.e6}, doi = {10.1016/j.forsciint.2017.10.005}, pmid = {29103902}, issn = {1872-6283}, mesh = {Adult ; Age Determination by Teeth/*methods ; Aged ; *Asian People ; Bicuspid/diagnostic imaging/*growth & development ; Dental Pulp/diagnostic imaging/*growth & development ; Female ; Forensic Dentistry ; Humans ; Linear Models ; Male ; Mandible ; Middle Aged ; Radiography, Dental, Digital ; Radiography, Panoramic ; Republic of Korea ; Young Adult ; }, abstract = {OBJECTIVES: This study aimed to examine the applicability of the pulp/tooth area ratio in the lower premolar teeth using panoramic radiography in age estimation of Korean adults.

METHODS: 402 digital panoramic images of Korean adults between 20 and 78 years were analyzed. Following Cameriere et al.'s method, two observers measured the pulp and tooth areas of the lower second premolar on digital panoramic images, and the ratio of pulp to tooth area in the whole tooth (PTR) was calculated. In addition, the whole tooth was divided into coronal and root parts at the cementoenamel junction, and the ratios in the coronal part (PcCR) and root part (PrRR) were also calculated separately. Independent t-test, Analysis of covariance, linear regression, and the standard error of the estimate (SEE) were computed using statistical software. To justify the use of linear regression models for purposes of prediction, diagnostic tests of principal assumptions were also performed.

RESULTS: Independent t-test revealed significant differences in genders. PrRR produced the best age correlation (male, SEE=10.8; female, SEE=9.8; total, SEE=10.4 years), followed closely by PTR (male, SEE=11.1; female, SEE=10.3; total, SEE=10.7 years) and a relatively lower accuracy for PcCR (male, SEE=14.7; female, SEE=14.4; total, SEE=14.6 years). Model assumptions and accuracy for purposes of prediction in PTR and PrRR were satisfied.

CONCLUSIONS: The pulp/tooth area ratio using panoramic radiography has the potential as an effective tool for age estimation in the Korean adult population, and the pulp/tooth area ratio in the root part is more accurate than that of the whole tooth. Notably, female has shown higher accuracy compare to male subject.}, } @article {pmid29103132, year = {2018}, author = {Zhong, Q and Xiong, A and Vu, KL and Proctor, RW}, title = {Vertically arrayed stimuli and responses: transfer of incompatible spatial mapping to Simon task occurs regardless of response-device orientation.}, journal = {Experimental brain research}, volume = {236}, number = {1}, pages = {175-185}, pmid = {29103132}, issn = {1432-1106}, mesh = {Adult ; Female ; Humans ; Male ; Pattern Recognition, Visual/*physiology ; *Practice, Psychological ; Psychomotor Performance/*physiology ; Space Perception/*physiology ; Transfer, Psychology/*physiology ; Young Adult ; }, abstract = {Conde et al. (Exp Brain Res 233:3313-3321, 2015) found that the Simon effect for vertically arrayed stimuli and responses was reduced after 100 prior practice trials with an incompatible mapping of the stimulus locations and responses. This finding was contrary to Vu's (Mem Cognit 35:1463-1471, 2007) finding of no transfer effect with 72 trials of prior practice. Conde et al. proposed that the different results were due to their responses being coded as top and bottom in the frontal plane, whereas Vu's were coded as far and near in the transverse plane. We conducted four experiments to test this possibility in which participants responded with keypresses using their thumbs on a numeric keypad held vertically (upright in the frontal plane) or horizontally (flat in the transverse plane). Experiment 1 showed that, without any prior practice, a similar sized Simon effect was obtained when the response device was oriented in the transverse plane as when it was oriented in the frontal plane. In Experiments 2 and 3 participants performed with the same device orientation in the incompatible practice and Simon transfer tasks, with orientation manipulated between-subjects in the former and within-subjects in the latter. The Simon effect was reduced in both cases, with no significant difference in transfer effect for transverse and frontal planes. In Experiment 4, the device orientation differed between the incompatible practice and Simon transfer tasks, and the Simon effect was reduced similarly across both response-device orientations. Thus, the differences between Conde et al.'s and Vu's findings cannot be attributed to the response-device orientation. Our results are consistent with the view that people code response locations in the transverse plane as top and bottom, rather than far and near, in agreement with the terminology of "top row" and "bottom row" for computer keyboards.}, } @article {pmid29100500, year = {2017}, author = {Hansen, LR and Pedersen, SB and Overgaard, C and Torp-Pedersen, C and Ullits, LR}, title = {Associations between the structural and functional aspects of social relations and poor mental health: a cross-sectional register study.}, journal = {BMC public health}, volume = {17}, number = {1}, pages = {860}, pmid = {29100500}, issn = {1471-2458}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Cross-Sectional Studies ; Denmark/epidemiology ; Family/*psychology ; Female ; Friends/*psychology ; Health Surveys ; Humans ; *Interpersonal Relations ; Logistic Models ; Male ; Mental Disorders/*epidemiology ; Middle Aged ; Registries ; Risk Assessment ; *Social Support ; Young Adult ; }, abstract = {BACKGROUND: Social relations influence mental health through different pathways. To capture the complexity of social relations, it is beneficial to consider both the structural (e.g., reachability of social network and social integration) and functional (e.g., instrumental and emotional support) aspects of the concept. Both aspects are rarely investigated simultaneously. This study aimed to examine the association between the structural and functional aspects of social relations and poor mental health.

METHODS: The study was designed as a cross-sectional register study. We used data on mental health and social relations from 15,839 individuals aged 16-92 years with a mean age of 49.0 years (SD 17.9) who responded to The North Denmark Region Health Survey 2013 among residents in Northern Jutland, Denmark. The 12-Item Short-Form Health Survey measured mental health; a cut-off point of 44.5 was used to dichotomize participants into poor and good mental health. The categorization of social relations was inspired by Berkman et al.'s conceptual model of social relations and health. The analyses were performed with survey logistic regression.

RESULTS: We found that 21.6% (n = 3422) of participants reported poor mental health, and 59% (n = 2020) of these were women. Being in contact with family and friends less than once a month statistically significantly increased the risk for poor mental health (Family OR = 1.78, 95% CI = 1.51-2.10 and Friends OR = 2.65, 95% CI = 2.30-3.06). The individuals who were not in contact with their network as often as they liked had a significantly higher risk for poor mental health (OR = 2.40, 95% CI = 2.20-2.62). Lack of instrumental support was associated with a higher risk for poor mental health (OR = 2.81, 95% CI = 2.26-3.48). We found an interaction between age and emotional support; the youngest population had the highest risk for poor mental health when they did not have access to emotional support (Young OR = 5.26, 95% CI = 3.91-7.09; Adult OR = 3.69, 95% CI = 3.17-4.30; and Elderly OR = 2.73, 95% CI = 2.23-3.34).

CONCLUSIONS: Both structural and functional aspects of social relations were associated with poor mental health in our study. Rarely being in contact with friends and a lack of network reachability were associated with poor mental health. Likewise, low levels of emotional and instrumental support were associated with poor mental health.}, } @article {pmid29100494, year = {2017}, author = {Wang, G and Speakman, JR}, title = {Response to Farrokhi et al.'s statistical comments on 'no seasonal variation in physical activity of Han Chinese living in Beijing'.}, journal = {The international journal of behavioral nutrition and physical activity}, volume = {14}, number = {1}, pages = {152}, pmid = {29100494}, issn = {1479-5868}, mesh = {Asian People ; Beijing ; China ; *Climate ; Exercise ; Humans ; *Seasons ; }, } @article {pmid29098392, year = {2018}, author = {Obara, S and Imaizumi, T and Hakozaki, T and Hosono, A and Iseki, Y and Sanbe, N and Murakawa, M}, title = {Evaluation of pharmacokinetic models of intravenous dexmedetomidine in sedated patients under spinal anesthesia.}, journal = {Journal of anesthesia}, volume = {32}, number = {1}, pages = {33-40}, pmid = {29098392}, issn = {1438-8359}, mesh = {Adult ; *Anesthesia, Spinal ; Dexmedetomidine/*pharmacokinetics ; Female ; Humans ; Hypnotics and Sedatives/*pharmacokinetics ; Infusions, Intravenous ; Male ; Middle Aged ; *Models, Biological ; }, abstract = {PURPOSE: Little information is available on the predictive ability of previously published pharmacokinetic models of dexmedetomidine in patients under spinal anesthesia. We evaluated nine published pharmacokinetic models that were constructed in different study settings.

METHODS: Sixteen patients received dexmedetomidine infusions after spinal anesthesia according to the manufacturer's recommended regimen (6 µg/kg/h over 10 min followed by 0.2-0.7 µg/kg/h) or target-controlled infusion (initial target of 1.5 ng/ml using the Dyck model). Dexmedetomidine concentrations were measured and median performance error (MDPE), median absolute performance error (MDAPE), and wobble were calculated.

RESULTS: A total of 84 blood samples were analyzed. The pharmacokinetic model reported by Hannivoort et al. had the greatest ability to predict dexmedetomidine concentrations (MDPE 5.6%, MDAPE 18.1%, and wobble 6.2%).

CONCLUSIONS: Hannivoort et al.'s pharmacokinetic model, constructed with a dataset obtained from healthy volunteers, can predict dexmedetomidine concentrations best during continuous infusion under spinal anesthesia.}, } @article {pmid29078981, year = {2018}, author = {Shichel, I and Tzelgov, J}, title = {Modulation of conflicts in the Stroop effect.}, journal = {Acta psychologica}, volume = {189}, number = {}, pages = {93-102}, doi = {10.1016/j.actpsy.2017.10.007}, pmid = {29078981}, issn = {1873-6297}, mesh = {Color ; Color Perception/*physiology ; *Conflict, Psychological ; Female ; Humans ; Male ; Reaction Time/*physiology ; Semantic Differential ; *Stroop Test ; Young Adult ; }, abstract = {The purpose of the current study was to evaluate the unique contribution of task conflict, semantic conflict and response conflict to the Stroop effect and to test how these conflicts are modulated by manipulating the proportion of neutral trials, known to affect the magnitude of the Stroop effect. In the first experiment, we employed the two-to-one paradigm (De Houwer, 2003) while adding neutral illegible stimuli, and in the second experiment, we employed two colors and four word colors. In both experiments, we created four congruency conditions (neutral, congruent and two kind of incongruent conditions-those that include response conflict and those that do not), which allowed decomposing the Stroop effect into three orthogonal conflicts. In both experiments, we also manipulated the proportion of neutral trials. Task conflict was defined by the contrast between illegible neutrals and color words, semantic conflict by the contrast between congruent and incongruent stimuli, and response conflict by contrasting the two kinds of incongruent stimuli. Our results showed that all conflicts contributed to the Stroop effect. Task conflict and semantic conflict were modulated by the proportion of neutrals but response conflict was not. These findings imply that task conflict and semantic conflict are part of the control loop of the Stroop effect, as conceptualized by Botvinick et al.'s (2001) conflict monitoring model. There is no clear evidence of the response conflict being part of the loop. To complete the picture, we also analyzed the conflicts in the Stroop task using the traditional dependent contrasts approach and found the basic pattern of results was similar. Thus, the main advantage of the orthogonal comparisons approach is the possibility to estimate the unique contribution of the conflicts contributing to the Stroop effect and their modulation of the Stroop phenomenon.}, } @article {pmid29073059, year = {2017}, author = {Weisman, K and Dweck, CS and Markman, EM}, title = {Rethinking people's conceptions of mental life.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {114}, number = {43}, pages = {11374-11379}, pmid = {29073059}, issn = {1091-6490}, mesh = {Adult ; Aged ; Cognition ; *Emotions ; Female ; Humans ; Male ; Mental Processes/*physiology ; Middle Aged ; Morals ; Nontherapeutic Human Experimentation ; *Social Perception ; }, abstract = {How do people make sense of the emotions, sensations, and cognitive abilities that make up mental life? Pioneering work on the dimensions of mind perception has been interpreted as evidence that people consider mental life to have two core components-experience (e.g., hunger, joy) and agency (e.g., planning, self-control) [Gray HM, et al. (2007) Science 315:619]. We argue that this conclusion is premature: The experience-agency framework may capture people's understanding of the differences among different beings (e.g., dogs, humans, robots, God) but not how people parse mental life itself. Inspired by Gray et al.'s bottom-up approach, we conducted four large-scale studies designed to assess people's conceptions of mental life more directly. This led to the discovery of an organization that differs strikingly from the experience-agency framework: Instead of a broad distinction between experience and agency, our studies consistently revealed three fundamental components of mental life-suites of capacities related to the body, the heart, and the mind-with each component encompassing related aspects of both experience and agency. This body-heart-mind framework distinguishes itself from Gray et al.'s experience-agency framework by its clear and importantly different implications for dehumanization, moral reasoning, and other important social phenomena.}, } @article {pmid29062293, year = {2017}, author = {Negrín, F and Hernández-Fernaud, E and Hess, S and Hernández, B}, title = {Discrimination of Urban Spaces with Different Level of Restorativeness Based on the Original and on a Shorter Version of Hartig et al.'s Perceived Restorativeness Scale.}, journal = {Frontiers in psychology}, volume = {8}, number = {}, pages = {1735}, pmid = {29062293}, issn = {1664-1078}, abstract = {Restorativeness is defined as the potential of the environment to re-establish certain cognitive capacities related to human information processing. The most frequently used instrument for evaluating the restorativeness of places is the Perceived Restorativeness Scale, proposed by Hartig et al. (1991). Later on, shorter versions of the Perceived Restorativeness Scale were proposed. The aim of this work is to evaluate the discriminatory capacity of the original and of a shorter Spanish version of the PRS, considering urban settings previously selected for having different level of restorativeness, according to expert's criteria. The study involved 244 students and used a 3 × 2 mixed experimental design, with two independent variables: Restorativeness of a place (between-subjects), which was manipulated by showing pictures of settings selected with varying levels of restorativeness (high, medium, low), and length of the scale (within-subjects), which was manipulated by asking subjects to fill in both the original and a shorter version of the PRS. The order of presentation of the two scales was counterbalanced. Results show an appropriate reliability for both version of the scale. Items of being-away, fascination, and coherence of the shorter scale correlate more strongly with the corresponding factor of the original scale, compared to the others factors. Both scales produce similar values for the perceived restorativeness of the different places, except for places with low restorativeness.}, } @article {pmid29061319, year = {2018}, author = {Sulpizio, S and Kuroda, K and Dalsasso, M and Asakawa, T and Bornstein, MH and Doi, H and Esposito, G and Shinohara, K}, title = {Discriminating between mothers' infant- and adult-directed speech: Cross-linguistic generalizability from Japanese to Italian and German.}, journal = {Neuroscience research}, volume = {133}, number = {}, pages = {21-27}, pmid = {29061319}, issn = {1872-8111}, support = {Z99 HD999999/ImNIH/Intramural NIH HHS/United States ; }, mesh = {Adult ; Algorithms ; *Cross-Cultural Comparison ; Female ; Generalization, Psychological/*physiology ; Germany ; Humans ; Infant ; Italy ; Japan ; *Linguistics ; Male ; Markov Chains ; *Mother-Child Relations ; Speech/*physiology ; *Speech Discrimination Tests ; Speech Perception/physiology ; }, abstract = {The aim of the present work was a cross-linguistic generalization of Inoue et al.'s (2011) algorithm for discriminating infant- (IDS) vs. adult-directed speech (ADS). IDS is the way in which mothers communicate with infants; it is a universal communicative property, with some cross-linguistic differences. Inoue et al. (2011) implemented a machine algorithm that, by using a mel-frequency cepstral coefficient and a hidden Markov model, discriminated IDS from ADS in Japanese. We applied the original algorithm to two other languages that are very different from Japanese - Italian and German - and then tested the algorithm on Italian and German databases of IDS and ADS. Our results showed that: First, in accord with the extant literature, IDS is realized in a similar way across languages; second, the algorithm performed well in both languages and close to that reported for Japanese. The implications for the algorithm are discussed.}, } @article {pmid29058473, year = {2018}, author = {Tran, H and Ross, MW and Diamond, PM and Berg, RC and Weatherburn, P and Schmidt, AJ}, title = {Structural Validation and Multiple Group Assessment of the Short Internalized Homonegativity Scale in Homosexual and Bisexual Men in 38 European Countries: Results From the European MSM Internet Survey.}, journal = {Journal of sex research}, volume = {55}, number = {4-5}, pages = {617-629}, doi = {10.1080/00224499.2017.1380158}, pmid = {29058473}, issn = {1559-8519}, mesh = {Adult ; Bisexuality/*psychology ; Europe ; Health Surveys ; Homophobia/*psychology ; Homosexuality, Male/*psychology ; Humans ; Internet ; Male ; Psychometrics/*instrumentation/*standards ; *Self Concept ; }, abstract = {Internalized homonegativity (IH) is the internalization of negative attitudes and assumptions about homosexual people by homosexual people themselves. To measure IH, Smolenski, Diamond, Ross, and Rosser (2010) and Ross, Rosser, and Smolenski (2010) revised the Reactions to Homosexuality Scale (RHS) to develop the Short Internalized Homonegativity Scale (SIHS) with eight items. Using the European Men Who Have Sex With Men Internet Survey (EMIS) data, with an analytic sample of 130,718 gay and bisexual men in 38 European countries, we confirmed the validity of the SIHS scale in both training and validation data, in strata of Ross, Berg, et al.'s (2013) three "homosexual discrimination" country clusters, of age, and of education level. However, the performance was less adequate in comparison of gay versus bisexually identified individuals. The latent SIHS structure contains only minor variations across these three strata. The seven-item scale performed as well as the eight-item scale. The SIHS is a promising candidate for standard IH measures, which is invariant across cultural, age, and educational strata.}, } @article {pmid29053715, year = {2017}, author = {Mehmood, Z and Chen, G and Li, J and Li, L and Alzahrani, B}, title = {A robust ECC based mutual authentication protocol with anonymity for session initiation protocol.}, journal = {PloS one}, volume = {12}, number = {10}, pages = {e0186044}, pmid = {29053715}, issn = {1932-6203}, mesh = {*Computer Security ; Models, Theoretical ; }, abstract = {Over the past few years, Session Initiation Protocol (SIP) is found as a substantial application-layer protocol for the multimedia services. It is extensively used for managing, altering, terminating and distributing the multimedia sessions. Authentication plays a pivotal role in SIP environment. Currently, Lu et al. presented an authentication protocol for SIP and profess that newly proposed protocol is protected against all the familiar attacks. However, the detailed analysis describes that the Lu et al.'s protocol is exposed against server masquerading attack and user's masquerading attack. Moreover, it also fails to protect the user's identity as well as it possesses incorrect login and authentication phase. In order to establish a suitable and efficient protocol, having ability to overcome all these discrepancies, a robust ECC-based novel mutual authentication mechanism with anonymity for SIP is presented in this manuscript. The improved protocol contains an explicit parameter for user to cope the issues of security and correctness and is found to be more secure and relatively effective to protect the user's privacy, user's masquerading and server masquerading as it is verified through the comprehensive formal and informal security analysis.}, } @article {pmid29052167, year = {2018}, author = {Rocklage, MD and Rucker, DD and Nordgren, LF}, title = {The Evaluative Lexicon 2.0: The measurement of emotionality, extremity, and valence in language.}, journal = {Behavior research methods}, volume = {50}, number = {4}, pages = {1327-1344}, doi = {10.3758/s13428-017-0975-6}, pmid = {29052167}, issn = {1554-3528}, mesh = {Attitude ; Behavioral Research/methods ; *Cognition ; Data Mining/*methods ; *Emotions ; Humans ; *Internet ; *Language ; Public Opinion ; *Speech ; *Writing ; }, abstract = {The rapid expansion of the Internet and the availability of vast repositories of natural text provide researchers with the immense opportunity to study human reactions, opinions, and behavior on a massive scale. To help researchers take advantage of this new frontier, the present work introduces and validates the Evaluative Lexicon 2.0 (EL 2.0)-a quantitative linguistic tool that specializes in the measurement of the emotionality of individuals' evaluations in text. Specifically, the EL 2.0 utilizes natural language to measure the emotionality, extremity, and valence of evaluative reactions and attitudes. The present article describes how we used a combination of 9 million real-world online reviews and over 1,500 participant judges to construct the EL 2.0 and an additional 5.7 million reviews to validate it. To assess its unique value, the EL 2.0 is compared with two other prominent text analysis tools-LIWC and Warriner et al.'s (Behavior Research Methods, 45, 1191-1207, 2013) wordlist. The EL 2.0 is comparatively distinct in its ability to measure emotionality and explains a significantly greater proportion of the variance in individuals' evaluations. The EL 2.0 can be used with any data that involve speech or writing and provides researchers with the opportunity to capture evaluative reactions both in the laboratory and "in the wild." The EL 2.0 wordlist and normative emotionality, extremity, and valence ratings are freely available from www.evaluativelexicon.com .}, } @article {pmid29049689, year = {2018}, author = {Naseri, H and Johansson, H and Brolin, K}, title = {A Nonlinear Viscoelastic Model for Adipose Tissue Representing Tissue Response at a Wide Range of Strain Rates and High Strain Levels.}, journal = {Journal of biomechanical engineering}, volume = {140}, number = {4}, pages = {}, doi = {10.1115/1.4038200}, pmid = {29049689}, issn = {1528-8951}, mesh = {Adipose Tissue/*cytology ; Biomechanical Phenomena ; Calibration ; *Elasticity ; *Finite Element Analysis ; Materials Testing ; *Nonlinear Dynamics ; Rheology ; *Stress, Mechanical ; Viscosity ; }, abstract = {Finite element human body models (FEHBMs) are nowadays commonly used to simulate pre- and in-crash occupant response in order to develop advanced safety systems. In this study, a biofidelic model for adipose tissue is developed for this application. It is a nonlinear viscoelastic model based on the Reese et al.'s formulation. The model is formulated in a large strain framework and applied for finite element (FE) simulation of two types of experiments: rheological experiments and ramped-displacement experiments. The adipose tissue behavior in both experiments is represented well by this model. It indicates the capability of the model to be used in large deformation and wide range of strain rates for application in human body models.}, } @article {pmid29048180, year = {2017}, author = {}, title = {"Meta-analyses and P-curves support robust cycle shifts in women's mate preferences: Reply to Wood and Carden (2014) and Harris, Pashler, and Mickes (2014)": Correction to Gildersleeve, Haselton, and Fales (2014).}, journal = {Psychological bulletin}, volume = {143}, number = {11}, pages = {iii}, doi = {10.1037/bul0000129}, pmid = {29048180}, issn = {1939-1455}, abstract = {Reports an error in "Meta-analyses and p-curves support robust cycle shifts in women's mate preferences: Reply to Wood and Carden (2014) and Harris, Pashler, and Mickes (2014)" by Kelly Gildersleeve, Martie G. Haselton and Melissa R. Fales (Psychological Bulletin, 2014[Sep], Vol 140[5], 1272-1280). In the article, all p-curve analyses examining the Context Moderation Hypothesis Prediction mistakenly included the p-value from Little, Jones, Burt, & Perrett (2007) Study 2 for the simple effect of fertility on attraction to facial symmetry in a short-term relationship context (p < .001). The analyses should have instead included the p-value for the fertility X relationship context interaction (p = .011). In addition, the p-curve analyses examining exact two-tailed p-values for the Cycle Shift Prediction should have included an additional p-value from Provost et al. (2008) Study 1 for the main effect of fertility on attraction to gait masculinity. The reported p-value for this effect was .05, making it ineligible for inclusion in p-curves of reported p-values. However, the exact recalculated two-tailed p-value was .049, making it eligible for inclusion in p-curves of exact p-values. The corrected p-curve of exact two-tailed p-values evaluating the Cycle Shift Prediction and Context Moderation Prediction (displayed in Figure 2) now includes a total of 15 p-values (N = 1442) is no longer significantly right skewed χ[2](30) = 41.25, p = .08. The corrected p-curve of exact two-tailed p-values evaluating the Cycle Shift Prediction, Context Moderation Prediction, and Partner Qualities Moderation Prediction (displayed in Figure 3) now includes a total of 21 p-values (N = 1707) and continues to be significantly right skewed Χ[2](42) = 69.83, p = .004. As part of this correction, the online supplemental materials have been updated. (The following abstract of the original article appeared in record 2014-35938-003.) Two meta-analyses evaluated shifts across the ovulatory cycle in women's mate preferences but reported very different findings. In this journal, we reported robust evidence for the pattern of cycle shifts predicted by the ovulatory shift hypothesis (Gildersleeve, Haselton, & Fales, 2014). However, Wood, Kressel, Joshi, and Louie (2014) claimed an absence of compelling support for this hypothesis and asserted that the few significant cycle shifts they observed were false positives resulting from publication bias, p-hacking, or other research artifacts. How could 2 meta-analyses of the same literature reach such different conclusions? We reanalyzed the data compiled by Wood et al. These analyses revealed problems in Wood et al.'s meta-analysis-some of which are reproduced in Wood and Carden's (2014) comment in the current issue of this journal-that led them to overlook clear evidence for the ovulatory shift hypothesis in their own set of effects. In addition, we present right-skewed p-curves that directly contradict speculations by Wood et al.; Wood and Carden; and Harris, Pashler, and Mickes (2014) that supportive findings in the cycle shift literature are false positives. Therefore, evidence from both of the meta-analyses and the p-curves strongly supports genuine, robust effects consistent with the ovulatory shift hypothesis and contradicts claims that these effects merely reflect publication bias, p-hacking, or other research artifacts. Unfounded speculations about p-hacking distort the research record and risk unfairly damaging researchers' reputations; they should therefore be made only on the basis of firm evidence. (PsycINFO Database Record}, } @article {pmid29043914, year = {2019}, author = {Durrani, K and Kempen, JH and Foster, CS and , }, title = {Authors Reply to Letter to the Editor- In Response to: Comment on Durrani et al.'s "Adalimumab for Ocular Inflammation".}, journal = {Ocular immunology and inflammation}, volume = {27}, number = {1}, pages = {71}, doi = {10.1080/09273948.2017.1379545}, pmid = {29043914}, issn = {1744-5078}, mesh = {Adalimumab ; Humans ; *Inflammation ; }, } @article {pmid29035778, year = {2017}, author = {Koen, J and Wassenaar, D and Mamotte, N}, title = {The 'over-researched community': An ethics analysis of stakeholder views at two South African HIV prevention research sites.}, journal = {Social science & medicine (1982)}, volume = {194}, number = {}, pages = {1-9}, doi = {10.1016/j.socscimed.2017.10.005}, pmid = {29035778}, issn = {1873-5347}, mesh = {Developing Countries ; *Ethics, Research ; HIV Infections/*prevention & control ; Humans ; Informed Consent/ethics ; Research/*trends ; Research Subjects/psychology ; South Africa ; Stakeholder Participation/*psychology ; }, abstract = {Health research in resource-limited, multi-cultural contexts raises complex ethical concerns. The term 'over-researched community' (ORC) has been raised as an ethical concern and potential barrier to community participation in research. However, the term lacks conceptual clarity and is absent from established ethics guidelines and academic literature. In light of the concern being raised in relation to research in low- and middle-income countries (LMICs), a critical and empirical exploration of the meaning of ORC was undertaken. Guided by Emanuel et al.'s (2004) eight principles for ethically sound research in LMICs, this study examines the relevance and meaning of the terms 'over-research' and 'over-researched community' through an analysis of key stakeholder perspectives at two South African research sites. Data were collected between August 2007 and October 2008. 'Over-research' was found to represent a conglomeration of ethical concerns often used as a proxy for standard research ethics concepts. 'Over-research' seemed fundamentally linked to disparate positions and perspectives between different stakeholders in the research interaction, arising from challenges in inter-stakeholder relationships. 'Over-research' might be interpreted to mean exploitation. However, exploitation itself could mean different things. Using the term may lead to obscured understanding of real or perceived ethical concerns, making it difficult to identify and address the underlying concerns. It is recommended that the term be carefully and critically interrogated for clarity when used in research ethics discourse. Because it represents other legitimate concerns, it should not be dismissed without careful exploration.}, } @article {pmid29020494, year = {2019}, author = {Ghembaza, MEA and Lounici, A}, title = {Comment on Durrani et al.'s "Adalimumab for Ocular Inflammation".}, journal = {Ocular immunology and inflammation}, volume = {27}, number = {1}, pages = {70}, doi = {10.1080/09273948.2017.1371312}, pmid = {29020494}, issn = {1744-5078}, mesh = {Adalimumab ; *Antibodies, Monoclonal ; Humans ; *Inflammation ; }, } @article {pmid29020492, year = {2019}, author = {Tripathy, K}, title = {Comment on Trad et al.'s "Update on Immunological Test (Quantiferon-TB Gold) Contribution in the Management of Tuberculosis-Related Ocular Inflammation".}, journal = {Ocular immunology and inflammation}, volume = {27}, number = {1}, pages = {138-139}, doi = {10.1080/09273948.2017.1371766}, pmid = {29020492}, issn = {1744-5078}, mesh = {Humans ; Inflammation ; Tuberculin Test ; *Tuberculosis ; }, } @article {pmid29019157, year = {2018}, author = {Guitard, D and Saint-Aubin, J and Tehan, G and Tolan, A}, title = {Does neighborhood size really cause the word length effect?.}, journal = {Memory & cognition}, volume = {46}, number = {2}, pages = {244-260}, pmid = {29019157}, issn = {1532-5946}, support = {GPIN-2015-04416//Natural Sciences and Engineering Research Council of Canada/International ; }, mesh = {Adult ; Humans ; Memory, Short-Term/*physiology ; Mental Recall/*physiology ; *Psycholinguistics ; Young Adult ; }, abstract = {In short-term serial recall, it is well-known that short words are remembered better than long words. This word length effect has been the cornerstone of the working memory model and a benchmark effect that all models of immediate memory should account for. Currently, there is no consensus as to what determines the word length effect. Jalbert and colleagues (Jalbert, Neath, Bireta, & Surprenant, 2011a; Jalbert, Neath, & Surprenant, 2011b) suggested that neighborhood size is one causal factor. In six experiments we systematically examined their suggestion. In Experiment 1, with an immediate serial recall task, multiple word lengths, and a large pool of words controlled for neighborhood size, the typical word length effect was present. In Experiments 2 and 3, with an order reconstruction task and words with either many or few neighbors, we observed the typical word length effect. In Experiment 4 we tested the hypothesis that the previous abolition of the word length effect when neighborhood size was controlled was due to a confounded factor: frequency of orthographic structure. As predicted, we reversed the word length effect when using short words with less frequent orthographic structures than the long words, as was done in both of Jalbert et al.'s studies. In Experiments 5 and 6, we again observed the typical word length effect, even if we controlled for neighborhood size and frequency of orthographic structure. Overall, the results were not consistent with the predictions of Jalbert et al. and clearly showed a large and reliable word length effect after controlling for neighborhood size.}, } @article {pmid28983139, year = {2017}, author = {Cardel, MI and Pavela, G and Dhurandhar, E and Allison, DB}, title = {Future Research Directions for the Insurance Hypothesis regarding Food Insecurity and Obesity.}, journal = {The Behavioral and brain sciences}, volume = {40}, number = {}, pages = {}, pmid = {28983139}, issn = {1469-1825}, support = {P30 DK079626/DK/NIDDK NIH HHS/United States ; T32 DK062710/DK/NIDDK NIH HHS/United States ; UL1 TR001427/TR/NCATS NIH HHS/United States ; P30 DK056336/DK/NIDDK NIH HHS/United States ; KL2 TR001429/TR/NCATS NIH HHS/United States ; }, mesh = {Body Mass Index ; Cross-Sectional Studies ; *Food Supply ; Humans ; Obesity ; *Poverty ; United States ; }, abstract = {This commentary discusses Nettle et al.'s "The Insurance Hypothesis" linking food insecurity to a high body mass index (BMI). Discussion about how the relationship between race/ethnicity and obesity in the United States is consistent with this hypothesis is presented. Potential ways forward to elucidate the validity of this hypothesis in humans through rigorous controlled trials is highlighted.}, } @article {pmid28979222, year = {2017}, author = {Tarasuik, J and Demaria, A and Kaufman, J}, title = {Transfer of Problem Solving Skills from Touchscreen to 3D Model by 3- to 6-Year-Olds.}, journal = {Frontiers in psychology}, volume = {8}, number = {}, pages = {1586}, pmid = {28979222}, issn = {1664-1078}, abstract = {Although much published research purports that young children struggle to solve problems from screen-based media and to transfer learning from a virtual to a physical modality, Huber et al. (2016)'s recent study on children solving the Tower of Hanoi (ToH) problem on a touchscreen app offers a clear counter example. Huber et al. (2016) reported that children transferred learning from media to the physical world. As this finding arguably differs from that of prior research in this area, the current study tests whether the Huber et al. (2016) results could be replicated. Additionally, we extended the scope of the Huber et al. (2016) work by testing a broader age range, including children as young as 3 years, and using a culturally distinct participant pool. The results of the current study verified Huber et al.'s (2016) conclusion that 4- to 6-year-old children are capable of transferring the ToH learning from touchscreen devices to the physical version of the puzzle. Children under 4 years of age, in contrast, showed little ability to improve at the ToH problem regardless of the practice modality-suggesting that a different problem-solving task is required to probe very young children's ability to learn from touchscreen apps.}, } @article {pmid28974800, year = {2017}, author = {Assis, FR and Morais, RMSC and Morais, AMMB}, title = {Osmotic dehydration with sorbitol combined with hot air convective drying of apple cubes.}, journal = {Journal of food science and technology}, volume = {54}, number = {10}, pages = {3152-3160}, pmid = {28974800}, issn = {0022-1155}, abstract = {The aim of the present work was to study the effect of the osmotic dehydration (OD) pre-treatment on the mass transfer kinetics and water activity (aw) of apple cubes during hot air drying. The adequacy of different mathematical models to describe the moisture content of the product during this process was also evaluated. Apple cubes were osmotically dehydrated with sucrose or sorbitol solutions at 60 °C, and then dried by air at 25-80 °C. Overall, the OD and rise of the air temperature resulted in an increased water loss rate and a reduction of the aw. The osmotic agent used in the OD was not relevant to the air drying kinetics, but the pre-treatment with sorbitol solutions produced dried samples with lower aw. Newton's, Page's, modified Page's, Henderson and Pabis', Two-term, Two-term exponential, Logarithmic, Midilli et al.'s models could describe the moisture content well during the air drying process.}, } @article {pmid28967975, year = {2018}, author = {Gjersvik, P}, title = {Psoriasis is More Prevalent than Indicated by Egeberg et al.'s Danish Study: A Comment.}, journal = {Acta dermato-venereologica}, volume = {98}, number = {1}, pages = {169}, doi = {10.2340/00015555-2809}, pmid = {28967975}, issn = {1651-2057}, mesh = {Humans ; Prevalence ; *Psoriasis ; }, } @article {pmid28964267, year = {2017}, author = {Power, J and McVeigh, J and Gilmore, B and MacLachlan, M}, title = {Opportunities for human resources for health and rehabilitation: a response to Jesus et al.}, journal = {Human resources for health}, volume = {15}, number = {1}, pages = {73}, pmid = {28964267}, issn = {1478-4491}, mesh = {*Health Resources ; Humans ; *Policy ; }, abstract = {We welcome Jesus et al.'s paper, which makes an important contribution to the under-researched area of the physical rehabilitation workforce. The authors present recommendations to "advance a policy and research agenda for ensuring that an adequate rehabilitation workforce can meet the current and future rehabilitation health needs" (p. 1). We argue that their perspective could however be strengthened by adopting a stronger global perspective, including consideration of the needs of low-resource settings. In particular, we highlight the integral role of more effective sector and inter-sectoral governance, the opportunity to support the development of community-based rehabilitation (CBR), the lessons that can be learnt from human resources for health (HRH) research and practice more generally, and the recent developments in the global provision of assistive technologies. Each of these issues has important implications and contributions to make to advance the policy and research agenda for the global rehabilitation workforce.}, } @article {pmid28952202, year = {2018}, author = {Meltzoff, AN and Murray, L and Simpson, E and Heimann, M and Nagy, E and Nadel, J and Pedersen, EJ and Brooks, R and Messinger, DS and Pascalis, L and Subiaul, F and Paukner, A and Ferrari, PF}, title = {Re-examination of Oostenbroek et al. (2016): evidence for neonatal imitation of tongue protrusion.}, journal = {Developmental science}, volume = {21}, number = {4}, pages = {e12609}, pmid = {28952202}, issn = {1467-7687}, support = {U54 HD083091/HD/NICHD NIH HHS/United States ; }, mesh = {Bias ; Brain/*physiology ; *Cognition ; Female ; Humans ; Imitative Behavior/*physiology ; Infant ; Infant, Newborn ; Research Design ; Social Learning ; }, abstract = {The meaning, mechanism, and function of imitation in early infancy have been actively discussed since Meltzoff and Moore's (1977) report of facial and manual imitation by human neonates. Oostenbroek et al. (2016) claim to challenge the existence of early imitation and to counter all interpretations so far offered. Such claims, if true, would have implications for theories of social-cognitive development. Here we identify 11 flaws in Oostenbroek et al.'s experimental design that biased the results toward null effects. We requested and obtained the authors' raw data. Contrary to the authors' conclusions, new analyses reveal significant tongue-protrusion imitation at all four ages tested (1, 3, 6, and 9 weeks old). We explain how the authors missed this pattern and offer five recommendations for designing future experiments. Infant imitation raises fundamental issues about action representation, social learning, and brain-behavior relations. The debate about the origins and development of imitation reflects its importance to theories of developmental science.}, } @article {pmid28951481, year = {2017}, author = {Price, LB}, title = {Bacterial Whack-a-Mole: Reconsidering the Public Health Relevance of Using Carbadox in Food Animals.}, journal = {mBio}, volume = {8}, number = {5}, pages = {}, pmid = {28951481}, issn = {2150-7511}, mesh = {Animals ; Anti-Bacterial Agents ; *Bacteriophages ; Carbadox ; *Gastrointestinal Microbiome ; Humans ; Public Health ; Swine ; Transcription, Genetic ; United States ; }, abstract = {Carbadox is an antibiotic used to control dysentery and promote growth in swine in the United States; however, the drug also causes tumors and birth defects in laboratory animals. Despite this and because the drug has no analogs in human medicine, it is not considered "medically important" and can be used in livestock without veterinarian oversight. In their recent study, T. A. Johnson et al. (mBio 8:e00709-17, 2017, https://doi.org/10.1128/mBio.00709-17) demonstrated that carbadox has profound effects on the swine gut microbiome, including the induction of transducing phage carrying tetracycline, aminoglycoside, and beta-lactam resistance genes. In swine production, carbadox can be used in conjunction with other antibiotics (e.g., oxytetracycline) that could fuel the emergence of strains carrying phage-encoded resistance determinants. Johnson et al.'s findings underscore the potential unforeseen consequences of using antibiotics in livestock production and call into question our current methods for classifying whether or not a veterinary drug has relevance to human health.}, } @article {pmid28926146, year = {2018}, author = {Rohde, E and Domm, E}, title = {Nurses' clinical reasoning practices that support safe medication administration: An integrative review of the literature.}, journal = {Journal of clinical nursing}, volume = {27}, number = {3-4}, pages = {e402-e411}, doi = {10.1111/jocn.14077}, pmid = {28926146}, issn = {1365-2702}, mesh = {Adult ; Decision Making ; Female ; *Health Knowledge, Attitudes, Practice ; Humans ; *Judgment ; Male ; Medication Errors/*nursing/*prevention & control/statistics & numerical data ; Middle Aged ; *Nurse's Role ; Nursing Staff, Hospital/*psychology ; }, abstract = {AIMS AND OBJECTIVES: To review the current literature about nurses' clinical reasoning practices that support safe medication administration.

BACKGROUND: The literature about medication administration frequently focuses on avoiding medication errors. Nurses' clinical reasoning used during medication administration to maintain medication safety receives less attention in the literature. As healthcare professionals, nurses work closely with patients, assessing and intervening to promote mediation safety prior to, during and after medication administration. They also provide discharge teaching about using medication safely. Nurses' clinical reasoning and practices that support medication safety are often invisible when the focus is medication errors avoidance.

DESIGN: An integrative literature review was guided by Whittemore and Knafl's (Journal of Advanced Nursing, 5, 2005 and 546) five-stage review of the 11 articles that met review criteria. This review is modelled after Gaffney et al.'s (Journal of Clinical Nursing, 25, 2016 and 906) integrative review on medical error recovery.

METHODS: Health databases were accessed and systematically searched for research reporting nurses' clinical reasoning practices that supported safe medication administration. The level and quality of evidence of the included research articles were assessed using The Johns Hopkins Nursing Evidence-Based Practice Rating Scale©.

RESULTS: Nurses have a central role in safe medication administration, including but not limited to risk awareness about the potential for medication errors. Nurses assess patients and their medication and use knowledge and clinical reasoning to administer medication safely. Results indicated nurses' use of clinical reasoning to maintain safe medication administration was inadequately articulated in 10 of 11 studies reviewed.

CONCLUSION: Nurses are primarily responsible for safe medication administration. Nurses draw from their foundational knowledge of patient conditions and organisational processes and use clinical reasoning that supports safe medication practice. There was minimal evidence clearly articulating nurses' clinical reasoning used to support medication safety.

This review focused on finding evidence of nurses' clinical reasoning that supported safe medication administration.}, } @article {pmid28925287, year = {2019}, author = {Cook, K and Tillard, G and Wyles, C and Gerhard, D and Ormond, T and McAuliffe, M}, title = {Assessing and developing the written reflective practice skills of speech-language pathology students.}, journal = {International journal of speech-language pathology}, volume = {21}, number = {1}, pages = {46-55}, doi = {10.1080/17549507.2017.1374463}, pmid = {28925287}, issn = {1754-9515}, mesh = {Adult ; Female ; Humans ; Male ; Middle Aged ; Speech-Language Pathology/*education ; Students ; Thinking ; Writing ; Young Adult ; }, abstract = {PURPOSE: Written reflective practice aims to support critical thinking and problem solving skills in speech-language pathology (SLP) clinical education programmes. Yet, there has been limited investigation of students' development of written reflective practice skills over time and during a real-time clinical experience. The purpose of this study was to investigate students' development of breadth and depth of written reflective practice across a six-week clinical experience.

METHOD: Participants were 59 undergraduate and 14 postgraduate SLP students. Participants wrote critical reflections describing an interaction with a client/s at the conclusion of weeks two, four and six of their clinical experience. Formative feedback was provided after each submission. Breadth and depth of reflection were coded using a modification of Plack et al.'s coding schema.

RESULT: There was a statistically significant association between time and likelihood of development of breadth of reflection for the elements process and content. Depth of reflection improved significantly across time. The majority of participants were classified as "reflectors" or critical reflector at the conclusion of the study.

CONCLUSION: SLP students can make significant improvements in both breadth and depth of written reflective practice over a six-week period. Implications for clinical teaching are discussed.}, } @article {pmid28915815, year = {2017}, author = {Gould, GS and Bar-Zeev, Y and Bovill, M and Atkins, L and Gruppetta, M and Clarke, MJ and Bonevski, B}, title = {Designing an implementation intervention with the Behaviour Change Wheel for health provider smoking cessation care for Australian Indigenous pregnant women.}, journal = {Implementation science : IS}, volume = {12}, number = {1}, pages = {114}, pmid = {28915815}, issn = {1748-5908}, mesh = {Adult ; Australia ; Counseling/*methods ; Female ; *Health Behavior ; Health Plan Implementation/*methods ; Health Promotion/*methods ; *Health Services, Indigenous ; Humans ; Smoking Cessation/*methods ; }, abstract = {BACKGROUND: Indigenous smoking rates are up to 80% among pregnant women: prevalence among pregnant Australian Indigenous women was 45% in 2014, contributing significantly to the health gap for Indigenous Australians. We aimed to develop an implementation intervention to improve smoking cessation care (SCC) for pregnant Indigenous smokers, an outcome to be achieved by training health providers at Aboriginal Medical Services (AMS) in a culturally competent approach, developed collaboratively with AMS.

METHOD: The Behaviour Change Wheel (BCW), incorporating the COM-B model (capability, opportunity and motivation for behavioural interventions), provided a framework for the development of the Indigenous Counselling and Nicotine (ICAN) QUIT in Pregnancy implementation intervention at provider and patient levels. We identified evidence-practice gaps through (i) systematic literature reviews, (ii) a national survey of clinicians and (iii) a qualitative study of smoking and quitting with Aboriginal mothers. We followed the three stages recommended in Michie et al.'s "Behaviour Change Wheel" guide.

RESULTS: Targets identified for health provider behaviour change included the following: capability (psychological capability, knowledge and skills) by training clinicians in pharmacotherapy to assist women to quit; motivation (optimism) by presenting evidence of effectiveness, and positive testimonials from patients and clinicians; and opportunity (environmental context and resources) by promoting a whole-of-service approach and structuring consultations using a flipchart and prompts. Education and training were selected as the main intervention functions. For health providers, the delivery mode was webinar, to accommodate time and location constraints, bringing the training to the services; for patients, face-to-face consultations were supported by a booklet embedded with videos to improve patients' capability, opportunity and motivation.

CONCLUSIONS: The ICAN QUIT in Pregnancy was an intervention to train health providers at Aboriginal Medical Services in how to implement culturally competent evidence-based practice including counselling and nicotine replacement therapy for pregnant patients who smoke. The BCW aided in scientifically and systematically informing this targeted implementation intervention based on the identified gaps in SCC by health providers. Multiple factors impact at systemic, provider, community and individual levels. This process was therefore important for defining the design and intervention components, prior to a conducting a pilot feasibility trial, then leading on to a full clinical trial.}, } @article {pmid28898710, year = {2017}, author = {Morean, DF}, title = {Effects of semantic weight on verb retrieval in individuals with aphasia: A different perspective.}, journal = {Journal of communication disorders}, volume = {69}, number = {}, pages = {119-129}, doi = {10.1016/j.jcomdis.2017.07.003}, pmid = {28898710}, issn = {1873-7994}, mesh = {Aphasia/*psychology ; Brief Psychiatric Rating Scale ; Female ; Humans ; Male ; Mental Recall/*physiology ; Middle Aged ; *Semantics ; *Vocabulary ; }, abstract = {The majority of people with aphasia have word retrieval difficulty and effective treatment remains elusive. There have been a few studies that have explored the effects of semantic complexity on verb retrieval in individuals with aphasia; each used a variation of Breedin et al.'s (1998) delayed repetition/story completion task. Although each subsequent investigator worked to address potential confounds in order to achieve more valid results that would give rise to a clearer understanding of these deficits, findings and their interpretations have varied. In our replication, groups of individuals with aphasia (9 agrammatic and 9 anomic) plus 12 age-matched controls participated in a story completion task that included novel distracter stories to prevent rehearsal. Additionally, stimuli were developed in strict adherence to novel semantic and syntactic templates to control for relevant factors, and stimuli were prerecorded to ensure uniform delivery. We calculated the number of target verbs produced and overall production of light and heavy verbs, and error analysis was performed with special attention to semantically appropriate substitutions. In contrast to previous studies, we found no significant performance differences on these measures within or between groups. Exploratory analyses were performed. Results are discussed in terms of relevant factors of verb retrieval and implications for future experimental design. Application to much-needed verb retrieval treatment is also considered.}, } @article {pmid28898436, year = {2018}, author = {Legro, RS}, title = {Letter to Liu et al.'s "Efficacy of Exenatide on weight loss, metabolic parameters and pregnancy in overweight/obese polycystic ovary syndrome".}, journal = {Clinical endocrinology}, volume = {88}, number = {4}, pages = {607}, doi = {10.1111/cen.13474}, pmid = {28898436}, issn = {1365-2265}, mesh = {Exenatide ; Female ; Humans ; Obesity ; Overweight ; *Polycystic Ovary Syndrome ; Pregnancy ; *Weight Loss ; }, } @article {pmid28891687, year = {2017}, author = {Chen, W and Hendrix, W and Samatova, NF}, title = {The Application of the Weighted k-Partite Graph Problem to the Multiple Alignment for Metabolic Pathways.}, journal = {Journal of computational biology : a journal of computational molecular cell biology}, volume = {24}, number = {12}, pages = {1195-1211}, doi = {10.1089/cmb.2017.0064}, pmid = {28891687}, issn = {1557-8666}, mesh = {*Algorithms ; Computational Biology/*methods ; Humans ; *Metabolic Networks and Pathways ; Protein Interaction Mapping ; Sequence Alignment ; }, abstract = {The problem of aligning multiple metabolic pathways is one of very challenging problems in computational biology. A metabolic pathway consists of three types of entities: reactions, compounds, and enzymes. Based on similarities between enzymes, Tohsato et al. gave an algorithm for aligning multiple metabolic pathways. However, the algorithm given by Tohsato et al. neglects the similarities among reactions, compounds, enzymes, and pathway topology. How to design algorithms for the alignment problem of multiple metabolic pathways based on the similarity of reactions, compounds, and enzymes? It is a difficult computational problem. In this article, we propose an algorithm for the problem of aligning multiple metabolic pathways based on the similarities among reactions, compounds, enzymes, and pathway topology. First, we compute a weight between each pair of like entities in different input pathways based on the entities' similarity score and topological structure using Ay et al.'s methods. We then construct a weighted k-partite graph for the reactions, compounds, and enzymes. We extract a mapping between these entities by solving the maximum-weighted k-partite matching problem by applying a novel heuristic algorithm. By analyzing the alignment results of multiple pathways in different organisms, we show that the alignments found by our algorithm correctly identify common subnetworks among multiple pathways.}, } @article {pmid28889806, year = {2018}, author = {Gorman, DM}, title = {Letter to the Editor: Sources of bias and need for caution in interpreting the results of Spoth et al.'s (2017) PROSPER study.}, journal = {Psychological medicine}, volume = {48}, number = {4}, pages = {694-696}, doi = {10.1017/S0033291717002355}, pmid = {28889806}, issn = {1469-8978}, mesh = {Adolescent ; Adult ; *Bias ; Humans ; *Risk-Taking ; }, } @article {pmid28887678, year = {2017}, author = {da Cunha Viana, A and Mendes, DL and de Andrade Lemes, LN and Thuler, LCS and Neves, DD and de Araújo-Melo, MH}, title = {Reply to Dijemeni et al.'s comments concerning: "The comparability of drug-induced sedation classification systems".}, journal = {European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery}, volume = {274}, number = {12}, pages = {4279-4280}, pmid = {28887678}, issn = {1434-4726}, mesh = {*Anesthesia ; Humans ; }, } @article {pmid28886736, year = {2017}, author = {Roncarolo, F and Boivin, A and Denis, JL and Hébert, R and Lehoux, P}, title = {What do we know about the needs and challenges of health systems? A scoping review of the international literature.}, journal = {BMC health services research}, volume = {17}, number = {1}, pages = {636}, pmid = {28886736}, issn = {1472-6963}, mesh = {Adolescent ; Aged ; Child ; *Delivery of Health Care ; Government Programs ; *Health Services Needs and Demand ; Humans ; Italy ; Leadership ; Medical Assistance ; Mental Health ; Primary Health Care ; }, abstract = {BACKGROUND: While there is an extensive literature on Health System (HS) strengthening and on the performance of specific HSs, there are few exhaustive syntheses of the challenges HSs are facing worldwide. This paper reports the findings of a scoping review aiming to classify the challenges of HSs investigated in the scientific literature. Specifically, it determines the kind of research conducted on HS challenges, where it was performed, in which health sectors and on which populations. It also identifies the types of challenge described the most and how they varied across countries.

METHODS: We searched 8 databases to identify scientific papers published in English, French and Italian between January 2000 and April 2016 that addressed HS needs and challenges. The challenges reported in the articles were classified using van Olmen et al.'s dynamic HS framework. Countries were classified using the Human Development Index (HDI). Our analyses relied on descriptive statistics and qualitative content analysis.

RESULTS: 292 articles were included in our scoping review. 33.6% of these articles were empirical studies and 60.1% were specific to countries falling within the very high HDI category, in particular the United States. The most frequently researched sectors were mental health (41%), infectious diseases (12%) and primary care (11%). The most frequently studied target populations included elderly people (23%), people living in remote or poor areas (21%), visible or ethnic minorities (15%), and children and adolescents (15%). The most frequently reported challenges related to human resources (22%), leadership and governance (21%) and health service delivery (24%). While health service delivery challenges were more often examined in countries within the very high HDI category, human resources challenges attracted more attention within the low HDI category.

CONCLUSIONS: This scoping review provides a quantitative description of the available evidence on HS challenges and a qualitative exploration of the dynamic relationships that HS components entertain. While health services research is increasingly concerned about the way HSs can adopt innovations, little is known about the system-level challenges that innovations should address in the first place. Within this perspective, four key lessons are drawn as well as three knowledge gaps.}, } @article {pmid28880882, year = {2017}, author = {Jensen, EA}, title = {Putting the methodological brakes on claims to measure national happiness through Twitter: Methodological limitations in social media analytics.}, journal = {PloS one}, volume = {12}, number = {9}, pages = {e0180080}, pmid = {28880882}, issn = {1932-6203}, mesh = {*Happiness ; Humans ; *Social Media ; Social Sciences ; }, abstract = {With the rapid global proliferation of social media, there has been growing interest in using this existing source of easily accessible 'big data' to develop social science knowledge. However, amidst the big data gold rush, it is important that long-established principles of good social research are not ignored. This article critically evaluates Mitchell et al.'s (2013) study, 'The Geography of Happiness: Connecting Twitter Sentiment and Expression, Demographics, and Objective Characteristics of Place', demonstrating the importance of attending to key methodological issues associated with secondary data analysis.}, } @article {pmid28872936, year = {2017}, author = {Sung, KM and Bernstein, K}, title = {Quantitative and Qualitative Evaluations of the Enhanced Logo-autobiography Program for Korean-American Women.}, journal = {Issues in mental health nursing}, volume = {38}, number = {12}, pages = {1005-1012}, doi = {10.1080/01612840.2017.1354104}, pmid = {28872936}, issn = {1096-4673}, mesh = {*Adaptation, Psychological ; Adult ; Asian/*psychology ; Autobiographies as Topic ; Depression/*ethnology/prevention & control ; Female ; Humans ; Korea/ethnology ; Middle Aged ; Personal Satisfaction ; Qualitative Research ; United States ; Wounds and Injuries/*psychology ; }, abstract = {This study extends Bernstein et al.'s (2016) investigation of the effects of the Enhanced Logo-autobiography Program on Korean-American women's depressive symptoms, coping strategies, purpose in life, and posttraumatic growth by analyzing quantitative and qualitative data. This study's participants significantly improved on quantitative measures of depression, coping strategies, purpose in life, and post-traumatic growth at eight weeks post-intervention and follow-up. The qualitative content analysis revealed 17 themes with five essential themes. The program's activity to promote purpose in life through posttraumatic growth facilitated participants' recovery from traumatic experiences. Standardized guidelines are needed to conduct this program in Korean community centers.}, } @article {pmid31085820, year = {2017}, author = {Costa de Santana, M and Duarte Mello Amoedo, C and Nascimento-Carvalho, CM}, title = {Clinical and epidemiological characteristics of children admitted with fever in emergency department with or without sepsis.}, journal = {Journal of infection in developing countries}, volume = {11}, number = {8}, pages = {597-603}, doi = {10.3855/jidc.9257}, pmid = {31085820}, issn = {1972-2680}, abstract = {INTRODUCTION: Sepsis is a major cause of childhood death worldwide. In developing countries, epidemiological data about sepsis is scarce. This study describes and compares the frequency of etiological agents and initial sites of infection in children with or without sepsis, identifying risk factors and assessing outcomes.

METHODOLOGY: Clinical and demographic data from patients < 13 years of age with reported fever in a pediatric emergency department were collected and registered in forms. Patients were classified as with or without sepsis according to Goldstein et al.'s criteria [6].

RESULTS: Of 254 patients, 120 (47%) did and 134 (53%) did not meet the sepsis definition. Overall, the median age (IQR) was 1.7 (0.8-3.9) years, and 153 (60%) were boys. Patients with sepsis were older (2.8 [1.1-5.3] versus 1.3 [0.6-2.9] years; p < 0.001) and had sickle-cell disease more frequently (7.6% versus 0.8%; p = 0.007). By multiple logistic regression, age and sickle-cell disease were independently associated with sepsis. The most frequent initial infections were pneumonia (43.7%), diarrhea (17.3%) and cellulitis/adenitis (13.0%). The frequency of these did not differ when patients with or without sepsis were compared. Etiology was established in 57 (22.4%) patients, 32 (26.7%), and 25 (18.7%) with or without sepsis, respectively. Four (3.3%) patients died in the sepsis subgroup, whereas none died in the other subgroup.

CONCLUSIONS: Children who met the 2005 international consensus definition of sepsis showed differences in age and comorbidities (sickle-cell disease) upon admission and were more likely to die.}, } @article {pmid28869780, year = {2017}, author = {Chao, A and Chiu, CH and Colwell, RK and Magnago, LFS and Chazdon, RL and Gotelli, NJ}, title = {Deciphering the enigma of undetected species, phylogenetic, and functional diversity based on Good-Turing theory.}, journal = {Ecology}, volume = {98}, number = {11}, pages = {2914-2929}, doi = {10.1002/ecy.2000}, pmid = {28869780}, issn = {0012-9658}, mesh = {*Biodiversity ; Brazil ; Ecology ; *Ecosystem ; Humans ; Phylogeny ; }, abstract = {Estimating the species, phylogenetic, and functional diversity of a community is challenging because rare species are often undetected, even with intensive sampling. The Good-Turing frequency formula, originally developed for cryptography, estimates in an ecological context the true frequencies of rare species in a single assemblage based on an incomplete sample of individuals. Until now, this formula has never been used to estimate undetected species, phylogenetic, and functional diversity. Here, we first generalize the Good-Turing formula to incomplete sampling of two assemblages. The original formula and its two-assemblage generalization provide a novel and unified approach to notation, terminology, and estimation of undetected biological diversity. For species richness, the Good-Turing framework offers an intuitive way to derive the non-parametric estimators of the undetected species richness in a single assemblage, and of the undetected species shared between two assemblages. For phylogenetic diversity, the unified approach leads to an estimator of the undetected Faith's phylogenetic diversity (PD, the total length of undetected branches of a phylogenetic tree connecting all species), as well as a new estimator of undetected PD shared between two phylogenetic trees. For functional diversity based on species traits, the unified approach yields a new estimator of undetected Walker et al.'s functional attribute diversity (FAD, the total species-pairwise functional distance) in a single assemblage, as well as a new estimator of undetected FAD shared between two assemblages. Although some of the resulting estimators have been previously published (but derived with traditional mathematical inequalities), all taxonomic, phylogenetic, and functional diversity estimators are now derived under the same framework. All the derived estimators are theoretically lower bounds of the corresponding undetected diversities; our approach reveals the sufficient conditions under which the estimators are nearly unbiased, thus offering new insights. Simulation results are reported to numerically verify the performance of the derived estimators. We illustrate all estimators and assess their sampling uncertainty with an empirical dataset for Brazilian rain forest trees. These estimators should be widely applicable to many current problems in ecology, such as the effects of climate change on spatial and temporal beta diversity and the contribution of trait diversity to ecosystem multi-functionality.}, } @article {pmid28864847, year = {2018}, author = {Zhao, F and Sun, F and Hou, Y and Chen, Y and Chen, D and Cao, X and Yi, H and Wang, B and He, X and Liang, J}, title = {A monocentric centerline extraction method for ring-like blood vessels.}, journal = {Medical & biological engineering & computing}, volume = {56}, number = {4}, pages = {695-707}, pmid = {28864847}, issn = {1741-0444}, support = {61601363//National Natural Science Foundation of China (CN)/ ; 11571012//National Natural Science Foundation of China (CN)/ ; }, mesh = {Algorithms ; Blood Vessels/*diagnostic imaging ; Computed Tomography Angiography ; Databases, Factual ; Humans ; Image Processing, Computer-Assisted/*methods ; Magnetic Resonance Angiography/*methods ; }, abstract = {Centerline is generally used to measure topological and morphological parameters of blood vessels, which is pivotal for the quantitative analysis of vascular diseases. However, previous centerline extraction methods have two drawbacks on complex blood vessels, represented as the failure on ring-like structures and the existing of multi-voxel width. In this paper, we propose a monocentric centerline extraction method for ring-like blood vessels, which consists of three components. First, multiple centerlines are generated from the seed points that are chosen by randomly sprinkling points on blood vessel data. Second, multi-centerline fusion is used to repair the notches of centerlines on ring-like vessels, and the local maximum of distance from oundary is employed to remedy the missing centerline points. Finally, monocentric processing is devised to keep the vascular centerline with single voxel width. We compared the proposed method with Wan et al.'s method and topological thinning on five groups of data including synthesized vascular datasets and MR brain images. The result showed the proposed method performed better than the two contrast methods both by visual inspection and by quantitative assessment, which demonstrated the performance of the proposed method on ring-like blood vessels as well as the elimination of multi-voxel width points.}, } @article {pmid28863718, year = {2020}, author = {Arana, FG and Rice, KG}, title = {Cross-Cultural Validity of the Ruminative Responses Scale in Argentina and the United States.}, journal = {Assessment}, volume = {27}, number = {2}, pages = {309-320}, doi = {10.1177/1073191117729204}, pmid = {28863718}, issn = {1552-3489}, mesh = {Adult ; Argentina ; Cross-Cultural Comparison ; *Emotions ; Female ; Humans ; Male ; Middle Aged ; *Perfectionism ; Personality Tests/*standards ; Psychometrics ; Students ; United States ; Universities ; Young Adult ; }, abstract = {Although frequently used in the United States, the Ruminative Response Scale (RRS) has not been extensively studied in cross-cultural samples. The present study evaluated the factor structure of Treynor et al.'s 10-item version of the RRS in samples from Argentina (N = 308) and the United States (N = 371). In addition to testing measurement invariance between the countries, we evaluated whether the maladaptive implications of rumination were weaker for the Argentinians than for the U.S. group. Self-critical perfectionism was the criterion in those tests. Partial scalar invariance supported an 8-item version of the RRS. There were no differences in factor means or factor correlations in RRS dimensions between countries. Brooding and Reflection were positively correlated with self-critical perfectionism in both countries, with no significant differences in the sizes of these relations between the two samples. Results are discussed in terms of psychometric and cross-cultural implications for rumination.}, } @article {pmid28863148, year = {2017}, author = {Greaves, RB and Dietmann, S and Smith, A and Stepney, S and Halley, JD}, title = {A conceptual and computational framework for modelling and understanding the non-equilibrium gene regulatory networks of mouse embryonic stem cells.}, journal = {PLoS computational biology}, volume = {13}, number = {9}, pages = {e1005713}, pmid = {28863148}, issn = {1553-7358}, support = {G1100526/MRC_/Medical Research Council/United Kingdom ; MC_PC_12009/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Animals ; Computational Biology/*methods ; Computer Simulation ; Gene Regulatory Networks/*genetics/*physiology ; Mice ; *Models, Genetic ; Mouse Embryonic Stem Cells/*physiology ; }, abstract = {The capacity of pluripotent embryonic stem cells to differentiate into any cell type in the body makes them invaluable in the field of regenerative medicine. However, because of the complexity of both the core pluripotency network and the process of cell fate computation it is not yet possible to control the fate of stem cells. We present a theoretical model of stem cell fate computation that is based on Halley and Winkler's Branching Process Theory (BPT) and on Greaves et al.'s agent-based computer simulation derived from that theoretical model. BPT abstracts the complex production and action of a Transcription Factor (TF) into a single critical branching process that may dissipate, maintain, or become supercritical. Here we take the single TF model and extend it to multiple interacting TFs, and build an agent-based simulation of multiple TFs to investigate the dynamics of such coupled systems. We have developed the simulation and the theoretical model together, in an iterative manner, with the aim of obtaining a deeper understanding of stem cell fate computation, in order to influence experimental efforts, which may in turn influence the outcome of cellular differentiation. The model used is an example of self-organization and could be more widely applicable to the modelling of other complex systems. The simulation based on this model, though currently limited in scope in terms of the biology it represents, supports the utility of the Halley and Winkler branching process model in describing the behaviour of stem cell gene regulatory networks. Our simulation demonstrates three key features: (i) the existence of a critical value of the branching process parameter, dependent on the details of the cistrome in question; (ii) the ability of an active cistrome to "ignite" an otherwise fully dissipated cistrome, and drive it to criticality; (iii) how coupling cistromes together can reduce their critical branching parameter values needed to drive them to criticality.}, } @article {pmid28856981, year = {2017}, author = {Cave, KR and Menneer, T and Nomani, MS and Stroud, MJ and Donnelly, N}, title = {Dual Target Search is Neither Purely Simultaneous nor Purely Successive.}, journal = {Quarterly journal of experimental psychology (2006)}, volume = {}, number = {}, pages = {1-29}, doi = {10.1080/17470218.2017.1307425}, pmid = {28856981}, issn = {1747-0226}, abstract = {Previous research shows that visual search for two different targets is less efficient than search for a single target. Stroud, Menneer, Cave and Donnelly (2012) concluded that two target colours are represented separately based on modeling the fixation patterns. Although those analyses provide evidence for two separate target representations, they do not show whether participants search simultaneously for both targets, or first search for one target and then the other. Some studies suggest that multiple target representations are simultaneously active, while others indicate that search can be voluntarily simultaneous, or switching, or a mixture of both. Stroud et al.'s participants were not explicitly instructed to use any particular strategy. These data were revisited to determine which strategy was employed. Each fixated item was categorised according to whether its colour was more similar to one target or the other. Once an item similar to one target is fixated, the next fixated item is more likely to be similar to that target than the other, showing that at a given moment during search, one target is generally favoured. However, the search for one target is not completed before search for the other begins. Instead, there are often short runs of one or two fixations to distractors similar to one target, with each run followed by a switch to the other target. Thus, the results suggest that one target is more highly weighted than the other at any given time, but not to the extent that search is purely successive.}, } @article {pmid28852119, year = {2017}, author = {Radiya-Dixit, E and Zhu, D and Beck, AH}, title = {Automated Classification of Benign and Malignant Proliferative Breast Lesions.}, journal = {Scientific reports}, volume = {7}, number = {1}, pages = {9900}, pmid = {28852119}, issn = {2045-2322}, support = {R21 CA187642/CA/NCI NIH HHS/United States ; }, mesh = {Algorithms ; Area Under Curve ; Breast/diagnostic imaging/metabolism/*pathology ; Breast Diseases/*diagnosis/diagnostic imaging/metabolism ; Breast Neoplasms/*diagnosis/diagnostic imaging/metabolism ; Female ; Humans ; *Models, Biological ; *Models, Statistical ; ROC Curve ; }, abstract = {Misclassification of breast lesions can result in either cancer progression or unnecessary chemotherapy. Automated classification tools are seen as promising second opinion providers in reducing such errors. We have developed predictive algorithms that automate the categorization of breast lesions as either benign usual ductal hyperplasia (UDH) or malignant ductal carcinoma in situ (DCIS). From diagnosed breast biopsy images from two hospitals, we obtained 392 biomarkers using Dong et al.'s (2014) computational tools for nuclei identification and feature extraction. We implemented six machine learning models and enhanced them by reducing prediction variance, extracting active features, and combining multiple algorithms. We used the area under the curve (AUC) of the receiver operating characteristic (ROC) curve for performance evaluation. Our top-performing model, a Combined model with Active Feature Extraction (CAFE) consisting of two logistic regression algorithms, obtained an AUC of 0.918 when trained on data from one hospital and tested on samples of the other, a statistically significant improvement over Dong et al.'s AUC of 0.858. Pathologists can substantially improve their diagnoses by using it as an unbiased validator. In the future, our work can also serve as a valuable methodology for differentiating between low-grade and high-grade DCIS.}, } @article {pmid28846696, year = {2017}, author = {Cardeña, E and Nordhjem, B and Marcusson-Clavertz, D and Holmqvist, K}, title = {The "hypnotic state" and eye movements: Less there than meets the eye?.}, journal = {PloS one}, volume = {12}, number = {8}, pages = {e0182546}, pmid = {28846696}, issn = {1932-6203}, mesh = {Adult ; Attention/*physiology ; Consciousness/*physiology ; Eye Movements/*physiology ; Female ; Humans ; Hypnosis/*methods ; Male ; Middle Aged ; Suggestion ; Young Adult ; }, abstract = {Responsiveness to hypnotic procedures has been related to unusual eye behaviors for centuries. Kallio and collaborators claimed recently that they had found a reliable index for "the hypnotic state" through eye-tracking methods. Whether or not hypnotic responding involves a special state of consciousness has been part of a contentious debate in the field, so the potential validity of their claim would constitute a landmark. However, their conclusion was based on 1 highly hypnotizable individual compared with 14 controls who were not measured on hypnotizability. We sought to replicate their results with a sample screened for High (n = 16) or Low (n = 13) hypnotizability. We used a factorial 2 (high vs. low hypnotizability) x 2 (hypnosis vs. resting conditions) counterbalanced order design with these eye-tracking tasks: Fixation, Saccade, Optokinetic nystagmus (OKN), Smooth pursuit, and Antisaccade (the first three tasks has been used in Kallio et al.'s experiment). Highs reported being more deeply in hypnosis than Lows but only in the hypnotic condition, as expected. There were no significant main or interaction effects for the Fixation, OKN, or Smooth pursuit tasks. For the Saccade task both Highs and Lows had smaller saccades during hypnosis, and in the Antisaccade task both groups had slower Antisaccades during hypnosis. Although a couple of results suggest that a hypnotic condition may produce reduced eye motility, the lack of significant interactions (e.g., showing only Highs expressing a particular eye behavior during hypnosis) does not support the claim that eye behaviors (at least as measured with the techniques used) are an indicator of a "hypnotic state." Our results do not preclude the possibility that in a more spontaneous or different setting the experience of being hypnotized might relate to specific eye behaviors.}, } @article {pmid28846007, year = {2017}, author = {Brown, NJL and Coyne, JC}, title = {Emodiversity: Robust predictor of outcomes or statistical artifact?.}, journal = {Journal of experimental psychology. General}, volume = {146}, number = {9}, pages = {1372-1377}, doi = {10.1037/xge0000330}, pmid = {28846007}, issn = {1939-2222}, mesh = {*Artifacts ; Ecosystem ; *Emotions ; Humans ; }, abstract = {This article examines the concept of emodiversity, put forward by Quoidbach et al. (2014) as a novel source of information about "the health of the human emotional ecosystem" (p. 2057). Quoidbach et al. drew an analogy between emodiversity as a desirable property of a person's emotional make-up and biological diversity as a desirable property of an ecosystem. They claimed that emodiversity was an independent predictor of better mental and physical health outcomes in two large-scale studies. Here, we show that Quoidbach et al.'s construct of emodiversity suffers from several theoretical and practical deficiencies, which make these authors' use of Shannon's (1948) entropy formula to measure emodiversity highly questionable. Our reanalysis of Quoidbach et al.'s two studies shows that the apparently substantial effects that these authors reported are likely due to a failure to conduct appropriate hierarchical regression in one case and to suppression effects in the other. It appears that Quoidbach et al.'s claims about emodiversity may reduce to little more than a set of computational and statistical artifacts. (PsycINFO Database Record}, } @article {pmid28840517, year = {2017}, author = {Vromen, J}, title = {Ultimate and proximate explanations of strong reciprocity.}, journal = {History and philosophy of the life sciences}, volume = {39}, number = {3}, pages = {25}, pmid = {28840517}, issn = {0391-9714}, mesh = {*Cooperative Behavior ; *Cultural Evolution ; Humans ; }, abstract = {Strong reciprocity (SR) has recently been subject to heated debate. In this debate, the "West camp" (West et al. in Evol Hum Behav 32(4):231-262, 2011), which is critical of the case for SR, and the "Laland camp" (Laland et al. in Science, 334(6062):1512-1516, 2011, Biol Philos 28(5):719-745, 2013), which is sympathetic to the case of SR, seem to take diametrically opposed positions. The West camp criticizes advocates of SR for conflating proximate and ultimate causation. SR is said to be a proximate mechanism that is put forward by its advocates as an ultimate explanation of human cooperation. The West camp thus accuses advocates of SR for not heeding Mayr's original distinction between ultimate and proximate causation. The Laland camp praises advocates of SR for revising Mayr's distinction. Advocates of SR are said to replace Mayr's uni-directional view on the relation between ultimate and proximate causes by the bi-directional one of reciprocal causation. The paper argues that both the West camp and the Laland camp misrepresent what advocates of SR are up to. The West camp is right that SR is a proximate cause of human cooperation. But rather than putting forward SR as an ultimate explanation, as the West camp argues, advocates of SR believe that SR itself is in need of ultimate explanation. Advocates of SR tend to take gene-culture co-evolutionary theory as the correct meta-theoretical framework for advancing ultimate explanations of SR. Appearances notwithstanding, gene-culture coevolutionary theory does not imply Laland et al.'s notion of reciprocal causation. "Reciprocal causation" suggests that proximate and ultimate causes interact simultaneously, while advocates of SR assume that they interact sequentially. I end by arguing that the best way to understand the debate is by disambiguating Mayr's ultimate-proximate distinction. I propose to reserve "ultimate" and "proximate" for different sorts of explanations, and to use other terms for distinguishing different kinds of causes and different parts of the total causal chain producing behavior.}, } @article {pmid28839417, year = {2017}, author = {Sannad, A and Tamgadge, S and Tamgadge, A and Yadav, KS and Giri, A and Wankhede, M}, title = {Total Serum Protein Estimation and Its Correlation with Clinical and Histopathological Grading using Masson's Trichrome Stain in Patients of Oral Submucous Fibrosis.}, journal = {Contemporary clinical dentistry}, volume = {8}, number = {2}, pages = {286-292}, pmid = {28839417}, issn = {0976-237X}, abstract = {OBJECTIVES: Oral submucous fibrosis (OSMF) caused by dense deposition of collagen fibers which is a protein. There is a plethora of research to evaluate degree of collagen deposition using various simple histochemical techniques, but its correlation with total serum protein (TSP) level has not been explored so far.

MATERIALS AND METHODS: This case-control study comprised total forty samples with thirty cases of OSMF and ten cases were selected as control group, divided into four groups as per Lai et al. classification. Histological grading was also done according to the Rooban et al.'s classification. Blood sample was collected to evaluate TSP estimation. Findings were tabulated, and comparisons were made between clinical, histological, and TSP estimation. Discrete statistical data were analyzed by Chi-square test, ANOVA, and t-test with a statistical analysis package (SPSS version software 6.0).

RESULTS: No significant correlation was obtained between clinical staging and histopathological grading. Definite correlation was obtained in TSP and globulin levels of OSMF patients and their grades of fibrosis histopathologically.

CONCLUSION: In the present study, it was observed that biochemical investigations involving assessment of TSP can be used as a diagnostic tool in OSMF, along with histopathological examination.}, } @article {pmid28837265, year = {2017}, author = {Beri, J and Nash, T and Martin, RM and Bereman, MS}, title = {Exposure to BMAA mirrors molecular processes linked to neurodegenerative disease.}, journal = {Proteomics}, volume = {17}, number = {17-18}, pages = {}, pmid = {28837265}, issn = {1615-9861}, support = {P30 ES025128/ES/NIEHS NIH HHS/United States ; T32 ES007046/ES/NIEHS NIH HHS/United States ; }, mesh = {Amino Acids, Diamino/*toxicity ; Amyotrophic Lateral Sclerosis/*chemically induced/metabolism/pathology ; Animals ; Cell Line ; Cyanobacteria Toxins ; Diet/adverse effects ; Excitatory Amino Acid Agonists/*toxicity ; Gene Expression Regulation/*drug effects ; Mice ; Motor Neurons/*metabolism/pathology ; Neuroblastoma/*metabolism/pathology ; }, abstract = {The goal of this study is to investigate the molecular pathways perturbed by in vitro exposure of beta-methylamino-L-alanine (BMAA) to NSC-34 cells via contemporary proteomics. Our analysis of differentially regulated proteins reveals significant enrichment (p < 0.01) of pathways related to ER stress, protein ubiquitination, the unfolded protein response, and mitochondrial dysfunction. Upstream regulator analysis indicates that exposure to BMAA induces activation of transcription factors (X-box binding protein 1; nuclear factor 2 erythroid like 2; promyelocytic leukemia) involved in regulation of the UPR, oxidative stress, and cellular senescence. Furthermore, the authors examine the hypothesis that BMAA causes protein damage via misincorporation in place of L-Serine. The authors are unable to detect misincorporation of BMAA into protein via analysis of cellular protein, secreted protein, targeted detection of BMAA after protein hydrolysis, or through the use of in vitro protein translation kits.}, } @article {pmid28831815, year = {2018}, author = {Lacanna, G}, title = {Commentary on Jeffrey Voigt et al.'s Article, "Private Rooms in Low Acuity Settings: A Systematic Review of Literature".}, journal = {HERD}, volume = {11}, number = {1}, pages = {78-81}, doi = {10.1177/1937586717724528}, pmid = {28831815}, issn = {2167-5112}, mesh = {*Patients' Rooms ; }, } @article {pmid28816514, year = {2017}, author = {Billieux, J and King, DL and Higuchi, S and Achab, S and Bowden-Jones, H and Hao, W and Long, J and Lee, HK and Potenza, MN and Saunders, JB and Poznyak, V}, title = {Functional impairment matters in the screening and diagnosis of gaming disorder.}, journal = {Journal of behavioral addictions}, volume = {6}, number = {3}, pages = {285-289}, pmid = {28816514}, issn = {2063-5303}, support = {001/WHO_/World Health Organization/International ; }, mesh = {*Behavior, Addictive ; *Disruptive, Impulse Control, and Conduct Disorders ; Humans ; International Classification of Diseases ; Internet ; *Video Games ; }, abstract = {This commentary responds to Aarseth et al.'s (in press) criticisms that the ICD-11 Gaming Disorder proposal would result in "moral panics around the harm of video gaming" and "the treatment of abundant false-positive cases." The ICD-11 Gaming Disorder avoids potential "overpathologizing" with its explicit reference to functional impairment caused by gaming and therefore improves upon a number of flawed previous approaches to identifying cases with suspected gaming-related harms. We contend that moral panics are more likely to occur and be exacerbated by misinformation and lack of understanding, rather than proceed from having a clear diagnostic system.}, } @article {pmid28816499, year = {2017}, author = {Shadloo, B and Farnam, R and Amin-Esmaeili, M and Hamzehzadeh, M and Rafiemanesh, H and Jobehdar, MM and Ghani, K and Charkhgard, N and Rahimi-Movaghar, A}, title = {Inclusion of gaming disorder in the diagnostic classifications and promotion of public health response.}, journal = {Journal of behavioral addictions}, volume = {6}, number = {3}, pages = {310-312}, pmid = {28816499}, issn = {2063-5303}, mesh = {*Behavior, Addictive ; Diagnostic and Statistical Manual of Mental Disorders ; Humans ; International Classification of Diseases ; Iran ; Public Health ; *Video Games ; }, abstract = {There are ongoing controversies regarding the upcoming ICD-11 concept of gaming disorder. Recently, Aarseth et al. have put this diagnostic entity into scrutiny. Although we, a group of Iranian researchers and clinicians, acknowledge some of Aarseth et al.'s concerns, believe that the inclusion of gaming disorder in the upcoming ICD-11 would facilitate necessary steps to raise public awareness, enhance development of proper diagnostic approaches and treatment interventions, and improve health and non-health policies.}, } @article {pmid28815374, year = {2018}, author = {Gu, X and Keller, MJ and Weiller-Abels, KH and Zhang, T}, title = {The roles of physical activity and sedentary behavior on Hispanic children's mental health: a motor skill perspective.}, journal = {Quality of life research : an international journal of quality of life aspects of treatment, care and rehabilitation}, volume = {27}, number = {1}, pages = {185-193}, pmid = {28815374}, issn = {1573-2649}, mesh = {Child, Preschool ; Exercise/physiology/*psychology ; Female ; Hispanic or Latino ; Humans ; Male ; Mental Health/*standards ; Motor Skills/*physiology ; Prospective Studies ; Quality of Life/*psychology ; Sedentary Behavior ; }, abstract = {PURPOSE: Motor competence (MC) has been recognized as the foundation for life-time moderate-to-vigorous physical activity (MVPA) as well as an influential factor in reducing sedentary behavior during childhood. Guided by Blair et al.'s health model, the purpose of this study was to examine the behavioral mechanism of mental health including physical, psychosocial, and cognitive health among Hispanic children related to MC and MVPA.

METHODS: A prospective research design was used with two-wave assessments across one academic year. A total of 141 Hispanic kindergarteners (Meanage = 5.37, SD = 0.48) were recruited in Texas. Nearly all (94.3%) of the participants were from low-income families based on the Income Eligibility Guidelines. The study was approved by the University Research Review Board, and informed consent was obtained from parents/guardians prior to starting the study.

RESULTS: Multiple regressions indicated that manipulative skill was a significant predictor of physical and psychosocial health (β = 0.21, β = 0.26, p < 0.05, respectively) and locomotor skill served as a significant predictor for cognitive health (β = 0.22, p < 0.01), after controlling for BMI. Bootstrapping analyses supported the statistical significance of indirect effects of MC on mental health outcomes through MVPA (95% CI [0.031, 0.119]) and sedentary behavior (95% CI [0.054, 0.235]), respectively.

CONCLUSION: The results suggest that skill-based activities/games, with instructions, should be encouraged during school-based physical activity and health promotion programs in childhood education. Better understanding of the early effects of MC may contribute to designing strategies to promote Hispanic children's well-being.}, } @article {pmid28813450, year = {2017}, author = {Chen, H and Peng, S and Dai, L and Zou, Q and Yi, B and Yang, X and Ma, ZS}, title = {Oral microbial community assembly under the influence of periodontitis.}, journal = {PloS one}, volume = {12}, number = {8}, pages = {e0182259}, pmid = {28813450}, issn = {1932-6203}, mesh = {Algorithms ; *Biodiversity ; Case-Control Studies ; Datasets as Topic ; Humans ; Metagenome ; Metagenomics/methods ; *Microbiota ; Models, Theoretical ; Mouth Mucosa/*microbiology ; Periodontitis/*microbiology ; }, abstract = {Several ecological hypotheses (e.g., specific plaque, non-specific plaque and keystone pathogen) regarding the etiology of periodontitis have been proposed since the 1990s, most of which have been centered on the concept of dysbiosis associated with periodontitis. Nevertheless, none of the existing hypotheses have presented mechanistic interpretations on how and why dysbiosis actually occurs. Hubbell's neutral theory of biodiversity offers a powerful null model to test hypothesis regarding the mechanism of community assembly and diversity maintenance from the metagenomic sequencing data, which can help to understand the forces that shape the community dynamics such as dysbiosis. Here we reanalyze the dataset from Abusleme et al.'s comparative study of the oral microbial communities from periodontitis patients and healthy individuals. Our study demonstrates that 14 out of 61 communities (23%) passed the neutrality test, a percentage significantly higher than the previous reported neutrality rate of 1% in human microbiome (Li & Ma 2016, Scientific Reports). This suggests that, while the niche selection may play a predominant role in the assembly and diversity maintenance in oral microbiome, the effect of neutral dynamics may not be ignored. However, no statistically significant differences in the neutrality passing rates were detected between the periodontitis and healthy treatments with Fisher's exact probability test and multiple testing corrections, suggesting that the mechanism of community assembly is robust against disturbances such as periodontitis. In addition, our study confirmed previous finding that periodontitis patients exhibited higher biodiversity. These findings suggest that while periodontitis may significantly change the community composition measured by diversity (i.e., the exhibition or 'phenotype' of community assembly), it does not seem to cause the 'mutation' of the 'genotype" (mechanism) of community assembly. We argue that the 'phenotypic' changes explain the observed link (not necessarily causal) between periodontitis and community dysbiosis, which is certainly worthy of further investigation.}, } @article {pmid28802111, year = {2018}, author = {Cao, Y and Wang, W and Li, W}, title = {Letter to the Editor Re: Yu Qing, Wang Hai-Jun, Wang Hong-Zhu, Li Yan, Liang Xiao-Min, Xu Chi, Jeppesen Erik Does the responses of Vallisneria natans (Lour.) Hara to high nitrogen loading differ between the summer high-growth season and the low-growth season? Science of the Total Environment 601-602(2017)1513-1521.}, journal = {The Science of the total environment}, volume = {610-611}, number = {}, pages = {75-76}, doi = {10.1016/j.scitotenv.2017.08.022}, pmid = {28802111}, issn = {1879-1026}, mesh = {Ammonium Compounds ; Animals ; Biomass ; Hydrocharitaceae/*growth & development ; Nitrogen/*chemistry ; *Phytoplankton ; *Seasons ; }, abstract = {Yu et al.'s paper showed very interesting effects of high nitrogen (N) on the submerged macrophytes Vallisneria natans: active growth in the growing season enabled the macrophytes partly to overcome the ammonium stress. This result was evident in an experiment using ten pond ecosystems; however, their conclusion that shading induced by high phytoplankton biomass together with the toxicity of high ammonium contributed to the decrease of macrophytes growth was not strongly supported by the data provided in the paper. Three factors influencing how submerged macrophytes respond to high ammonium, not addressed by Yu et al.'s paper, are toxicity of ammonium/ammonia (NH4[+]/NH3), the precise extent of shading in water and species-specific characteristics of macrophytes. In conclusion, a comprehensive consideration of abiotic and biotic factors that involve in the responses of submerged macrophytes to high N is urged in future studies of the role of high N on the growth of submerged macrophytes.}, } @article {pmid28796478, year = {2017}, author = {Ayemoba, O and Cuesta, A}, title = {Spectroscopic Evidence of Size-Dependent Buffering of Interfacial pH by Cation Hydrolysis during CO2 Electroreduction.}, journal = {ACS applied materials & interfaces}, volume = {9}, number = {33}, pages = {27377-27382}, doi = {10.1021/acsami.7b07351}, pmid = {28796478}, issn = {1944-8252}, abstract = {The nature of the electrolyte cation is known to affect the Faradaic efficiency and selectivity of CO2 electroreduction. Singh et al. (J. Am. Chem. Soc. 2016, 138, 13006-13012) recently attributed this effect to the buffering ability of cation hydrolysis at the electrical double layer. According to them, the pKa of hydrolysis decreases close to the cathode due to the polarization of the solvation water molecules sandwiched between the cation's positive charge and the negative charge on the electrode surface. We have tested this hypothesis experimentally, by probing the pH at the gold-electrolyte interface in situ using ATR-SEIRAS. The ratio between the integrated intensity of the CO2 and HCO3[-] bands, which has to be inversely proportional to the concentration of H[+], provided a means to determining the pH change at the electrode-electrolyte interface in situ during the electroreduction of CO2. Our results confirm that the magnitude of the pH increase at the interface follows the trend Li[+] > Na[+] > K[+] > Cs[+], adding strong experimental support to Singh's et al.'s hypothesis. We show, however, that the pH buffering effect was overestimated by Singh et al., their overestimation being larger the larger the cation. Moreover, our results show that the activity trend of the alkali-metal cations can be inverted in the presence of impurities that alter the buffering effect of the electrolyte, although the electrolyte with maximum activity is always that for which the increase in the interfacial pH is smaller.}, } @article {pmid28789989, year = {2017}, author = {Lemoine, S and Jost, D and Chabernaud, JL and Tourtier, JP}, title = {Reply to Letter: Re: Dell'Orto et al.'s letter "Feasibility of whole body hypothermia for neonates without congenital heart defects surviving in-hospital cardiac arrest unrelated to perinatal asphyxia": Whole-Body hypothermia after In-Hospital cardiac arrest. reply to Dell'Orto et al.}, journal = {Resuscitation}, volume = {119}, number = {}, pages = {e9}, doi = {10.1016/j.resuscitation.2017.07.034}, pmid = {28789989}, issn = {1873-1570}, mesh = {*Asphyxia ; Female ; Heart Arrest ; Heart Defects, Congenital ; Humans ; *Hypothermia ; Hypothermia, Induced ; Infant, Newborn ; Pregnancy ; }, } @article {pmid28783561, year = {2017}, author = {Kong, EH and Deatrick, JA and Bradway, CK}, title = {Men's experiences after prostatectomy: A meta-synthesis.}, journal = {International journal of nursing studies}, volume = {74}, number = {}, pages = {162-171}, doi = {10.1016/j.ijnurstu.2017.07.013}, pmid = {28783561}, issn = {1873-491X}, mesh = {Humans ; Male ; Prostatectomy/*psychology ; Qualitative Research ; }, abstract = {OBJECTIVE: The purpose of this review was to critically analyze, interpret, and synthesize the literature on men's experiences after prostatectomy.

DESIGN: A meta-synthesis was conducted.

DATA SOURCES: Six databases (PubMed, EMBASE, CINAHL, PsycINFO, AgeLine, and Sociological Abstract) were searched from the earliest year to 2016. From initial searches with main keywords (prostatectomy and qualitative study), 642 abstracts were retrieved. Based on inclusion criteria (English-language published qualitative study focusing on the experience of men after prostatectomy), this meta-synthesis included 15 studies.

REVIEW METHODS: Components of meta-study (meta-data-analysis, meta-method, and meta-theory) were employed to analyze, interpret, and synthesize the results of included studies. Three authors independently appraised the methodological quality of the included studies using a combined appraisal tool (The Critical Appraisal Skills Programme Qualitative Research Checklist and Paterson et al.'s Primary Research Appraisal Tool). The Enhancing Transparency in Reporting the Synthesis of Qualitative Research Statement was used to strengthen the completeness of reporting.

RESULTS: Fifteen studies met inclusion criteria and quality appraisal guidelines, however, most did not identify or relate their findings to theory. Through meta-synthesis, five themes emerged: facing a life-changing situation, experiencing changes and their impact, striving to manage and adjust to changes, coping with masculinity, and anticipating the future.

CONCLUSIONS: After prostatectomy, men experienced physical, psychological, and social changes. Many men are physically and psychologically ill-prepared and suffer from lack of information and support. Health care providers need to be sensitive to men's needs including perceptions of masculinity, realize the importance of support as an essential component of men's adaptation post-prostatectomy, and provide comprehensive and individualized patient-centered interventions. Future studies need to use rigorous research methods, clearly identify methodological approaches, and consider employing or developing theory.}, } @article {pmid28773769, year = {2016}, author = {Wu, HC and Chen, HH and Zhu, YR}, title = {Effects of Al-Impurity Type on Formation Energy, Crystal Structure, Electronic Structure, and Optical Properties of ZnO by Using Density Functional Theory and the Hubbard-U Method.}, journal = {Materials (Basel, Switzerland)}, volume = {9}, number = {8}, pages = {}, pmid = {28773769}, issn = {1996-1944}, abstract = {We systematically investigated the effects of Al-impurity type on the formation energy, crystal structure, charge density, electronic structure, and optical properties of ZnO by using density functional theory and the Hubbard-U method. Al-related defects, such as those caused by the substitution of Zn and O atoms by Al atoms (Als(Zn) and Als(O), respectively) and the presence of an interstitial Al atom at the center of a tetrahedron (Ali(tet)) or an octahedron (Ali(oct)), and various Al concentrations were evaluated. The calculated formation energy follows the order Ef(Als(Zn)) < Ef(Ali(tet)) < Ef(Ali(oct)) < Ef(Als(O)). Electronic structure analysis showed that the Als(Zn), Als(O), Ali(tet), and Ali(oct) models follow n-type conduction, and the optical band gaps are higher than that of pure ZnO. The calculated carrier concentrations of the Als(O) and Ali(tet)/Ali(oct) models are higher than that of the Als(Zn) model. However, according to the curvature of the band structure, the occurrence of interstitial Al atoms or the substitution of O atoms by Al atoms results in a high effective mass, possibly reducing the carrier mobility. The average transmittance levels in the visible light and ultraviolet (UV) regions of the Als(Zn) model are higher than those of pure ZnO. However, the presence of an interstitial Al atom within the ZnO crystal reduces transmittance in the visible light region; Als(O) substantially reduces the transmittance in the visible light and UV regions. In addition, the properties of ZnO doped with various Als(Zn) concentrations were analyzed.}, } @article {pmid28770410, year = {2017}, author = {Wells, JE and McGee, MA and Beautrais, AL}, title = {Response to Greaves et al.'s (2017) "The Diversity and Prevalence of Sexual Orientation Self-Labels in a New Zealand National Sample".}, journal = {Archives of sexual behavior}, volume = {46}, number = {8}, pages = {2207-2208}, doi = {10.1007/s10508-017-1047-9}, pmid = {28770410}, issn = {1573-2800}, mesh = {Female ; Humans ; Male ; New Zealand ; Prevalence ; *Sexual Behavior ; *Sexuality ; }, } @article {pmid28766782, year = {2017}, author = {Howe, N}, title = {PREDICTING NORMATIVE AND PROBLEMATIC FAMILY PATHWAYS TO THE TRANSITION TO SIBLINGHOOD: COMMENTARY ON VOLLING ET AL.'S MONOGRAPH.}, journal = {Monographs of the Society for Research in Child Development}, volume = {82}, number = {3}, pages = {184-195}, doi = {10.1111/mono.12319}, pmid = {28766782}, issn = {1540-5834}, abstract = {Volling et al.'s monograph provides a rich, thoughtful, and rigorous account of how the transition to siblinghood is experienced by the first-born child and the family. In their comprehensive longitudinal study, they followed 241 families from the prenatal period before the second-born's birth until this child was 12-months old. Siblings are a critical, but understudied, relationship in children's development; the challenges posed in researching sibling dynamics in the context of the family are discussed. Prior psychodynamic and developmental research literature is critiqued, which places the current study into perspective and indicates the important theoretical frameworks (i.e., developmental psychopathology and developmental ecological systems) employed by Volling et al. to advance our understanding of this critical transition in the life of the family. The longitudinal study design, sample characteristics, identification of possible trajectories of adjustment (or not) to the birth of the sibling, and selection of family and child variables are addressed. The sophisticated statistical methods (Growth Mixture Modeling and data mining procedures) employed to predict child adjustment in association with parenting variables over time and sibling relationship quality at 12 months identified low- and high-risk trajectories on the seven subscales of the Child Behavior Check List (CBCL). This afforded a nuanced investigation of a variety of potentially problematic child behaviors (e.g., aggression, withdrawal, negative emotionality, somatic problems) in association with parenting behaviors. A final discussion included study limitations, significant strengths, and implications for clinicians and other professionals. The study's conclusion is that most children and families are resilient, take the birth of a sibling in their stride, and do not exhibit empirical evidence of a developmental crisis, as argued by earlier psychodynamic authors.}, } @article {pmid28761013, year = {2017}, author = {Feldman, MW and Odling-Smee, J and Laland, KN}, title = {Why Gupta et al.'s critique of niche construction theory is off target.}, journal = {Journal of genetics}, volume = {96}, number = {3}, pages = {505-508}, pmid = {28761013}, issn = {0973-7731}, mesh = {Adaptation, Physiological/genetics ; Algorithms ; Animals ; *Biological Evolution ; *Ecosystem ; *Environment ; Genotype ; Humans ; *Models, Theoretical ; Phenotype ; }, abstract = {Gupta et al., in their article in this issue ('Niche construction in evolutionary theory: the construction of an academic niche?'. doi:10.1007/s12041-017-0787-6), lament 'serious problems with the way science is being done' and suggest that 'niche construction theory exemplifies this state of affairs.' However, their aggressively confrontational but superficial critique of niche construction theory (NCT) only contributes to these problems by attacking claims that NCT does not make. This is unfortunate, as their poor scholarship has done a disservice to the evolutionary biology community through propagating misinformation.We correct Gupta et al.'s misunderstandings, stressing that NCT does not suggest that the fact that organisms engage in niche construction is neglected, nor does it make strong claims on the basis of its formal theory. Moreover, the treatment of niche construction as an evolutionary process has been highly productive, and is both theoretically and empirically well-validated.We end by reflecting on the potentially deleterious implications of their publication for evolutionary science.}, } @article {pmid28758789, year = {2017}, author = {Shanks, DR}, title = {Misunderstanding the behavior priming controversy: Comment on Payne, Brown-Iannuzzi, and Loersch (2016).}, journal = {Journal of experimental psychology. General}, volume = {146}, number = {8}, pages = {1216-1222}, doi = {10.1037/xge0000307}, pmid = {28758789}, issn = {1939-2222}, mesh = {Humans ; *Motor Activity ; Reproducibility of Results ; }, abstract = {There has been considerable controversy around the limits and reproducibility of so-called "behavior" priming effects. Payne, Brown-Iannuzzi, and Loersch (2016) reported a series of 6 experiments on the effects of primes on participants' bets in a simulated blackjack game, and claimed that their findings not only establish the reality of behavior priming beyond dispute, but also demonstrate that this form of priming has the crucial hallmark of occurring outside participants' awareness and control. I describe a statistical model that does not distinguish automatic and controlled processes, but which nonetheless reproduces Payne et al.'s (2016) results and hence shows that their conclusions are unwarranted. Payne et al.'s (2016) experimental task and within-subjects design provide little insight into why some behavior priming studies have proven difficult to replicate. (PsycINFO Database Record}, } @article {pmid28749149, year = {2017}, author = {Song, QC and Wee, S and Newman, DA}, title = {Diversity shrinkage: Cross-validating pareto-optimal weights to enhance diversity via hiring practices.}, journal = {The Journal of applied psychology}, volume = {102}, number = {12}, pages = {1636-1657}, doi = {10.1037/apl0000240}, pmid = {28749149}, issn = {1939-1854}, mesh = {Adult ; Humans ; *Models, Statistical ; Personnel Selection/*statistics & numerical data ; Psychology, Industrial/*methods ; }, abstract = {To reduce adverse impact potential and improve diversity outcomes from personnel selection, one promising technique is De Corte, Lievens, and Sackett's (2007) Pareto-optimal weighting strategy. De Corte et al.'s strategy has been demonstrated on (a) a composite of cognitive and noncognitive (e.g., personality) tests (De Corte, Lievens, & Sackett, 2008) and (b) a composite of specific cognitive ability subtests (Wee, Newman, & Joseph, 2014). Both studies illustrated how Pareto-weighting (in contrast to unit weighting) could lead to substantial improvement in diversity outcomes (i.e., diversity improvement), sometimes more than doubling the number of job offers for minority applicants. The current work addresses a key limitation of the technique-the possibility of shrinkage, especially diversity shrinkage, in the Pareto-optimal solutions. Using Monte Carlo simulations, sample size and predictor combinations were varied and cross-validated Pareto-optimal solutions were obtained. Although diversity shrinkage was sizable for a composite of cognitive and noncognitive predictors when sample size was at or below 500, diversity shrinkage was typically negligible for a composite of specific cognitive subtest predictors when sample size was at least 100. Diversity shrinkage was larger when the Pareto-optimal solution suggested substantial diversity improvement. When sample size was at least 100, cross-validated Pareto-optimal weights typically outperformed unit weights-suggesting that diversity improvement is often possible, despite diversity shrinkage. Implications for Pareto-optimal weighting, adverse impact, sample size of validation studies, and optimizing the diversity-job performance tradeoff are discussed. (PsycINFO Database Record}, } @article {pmid28734576, year = {2017}, author = {Negreiros, A and Padula, RS and Andrea Bretas Bernardes, R and Moraes, MV and Pires, RS and Chiavegato, LD}, title = {Predictive validity analysis of six reference equations for the 6-minute walk test in healthy Brazilian men: a cross-sectional study.}, journal = {Brazilian journal of physical therapy}, volume = {21}, number = {5}, pages = {350-356}, pmid = {28734576}, issn = {1809-9246}, mesh = {Brazil ; Cross-Sectional Studies ; Exercise Tolerance/*physiology ; Hand Strength/*physiology ; Humans ; Male ; Walk Test/*methods ; }, abstract = {BACKGROUND: The six-minute walk test (6MWT) is an important tool for evaluating functional capacity and exercise tolerance. The reference equations for the 6MWT in healthy subjects were established on the basis of American and European populations, but reference equations have been proposed with different variables for the Brazilian population.

OBJECTIVE: To analyze the predictive validity of six reference equations for the six-minute walking distance (6MWD) in healthy adult men.

METHODS: We evaluated 103 individuals in relation to level of physical activity (IPAQ), respiratory symptoms (MRC), handgrip strength, and 6MWD test. The data were submitted to a normality test, then the Bland-Altman agreement test was used to compare individual 6MWD values with that expected for each equation.

RESULTS: The subjects were active, with a mean age of 34.12 (SD=8.88) years and no respiratory symptoms. The mean of the 6MWD was 663.43 (SD=93.01)m. The 6MWD's predicted values came closest to the walked distance covered by Britto et al.'s equation (using BMI) of 647.62 (SD=38.62)m.

CONCLUSIONS: The equation proposed by Britto et al. using body mass index (BMI) was the closest to the 6MWD for the individuals studied and could be widely used as a reference tool during the 6MWT in healthy Brazilian men.}, } @article {pmid28733953, year = {2017}, author = {Liu, XS and de Bakker, CMJ and Tseng, WJ and Li, Y and Zhao, H}, title = {Response to Loucks et al.'s Comment on "Clinical Evaluation of Bone Strength and Fracture Risk".}, journal = {Current osteoporosis reports}, volume = {15}, number = {4}, pages = {398}, pmid = {28733953}, issn = {1544-2241}, mesh = {Bone Density ; *Fractures, Bone ; Humans ; Risk Factors ; }, } @article {pmid28726482, year = {2017}, author = {Nielsen, E and Kirtley, OJ and Townsend, E}, title = {"Great powers and great responsibilities": A brief comment on "A brief mobile app reduces nonsuicidal and suicidal self-injury: Evidence from three randomized controlled trials" (Franklin et al., 2016).}, journal = {Journal of consulting and clinical psychology}, volume = {85}, number = {8}, pages = {826-830}, doi = {10.1037/ccp0000189}, pmid = {28726482}, issn = {1939-2117}, mesh = {Humans ; Mental Health ; *Mobile Applications ; Randomized Controlled Trials as Topic ; Self-Injurious Behavior/*prevention & control ; Suicidal Ideation ; }, abstract = {Online and mobile mental health applications (apps) herald exciting new opportunities for the treatment and prevention of self-injurious thoughts and behaviors (SITBs). With such rapid technological advances, it is paramount that health care innovation not be achieved to the detriment of intervention quality. Franklin et al.'s (2016) therapeutic evaluative conditioning (TEC) app is a novel and timely addition to the mobile health landscape; uncommonly for such apps, it is evidence based. There are, however, several crucial challenges to be surmounted for TEC to be successful; arguably, interventions ought to build lasting skills that can be subsequently and consciously recruited to manage distress beyond the intervention period. Furthermore, SITBs are a coping mechanism (albeit maladaptive); thus, extinguishing SITBs via TEC must be bolstered by the development of alternative coping strategies, particularly if the psychological distress that underlies SITBs is not addressed therapeutically. Stigma exacerbates the psychological distress of those engaging in SITBs; therefore, we question whether the types of stimuli employed in TEC may further add to this stigma, potentially affecting future help seeking. One solution may be to explore a positive-only TEC; enhancing positive self-worth may provide a more sustainable and meaningful treatment target, particularly when used as an adjunct to therapy or as a waiting list intervention. Mobile interventions for SITBs bring unique ethical challenges, including individuals' right to be fully informed about potentially distressing stimuli. This commentary aims to highlight the methodological and ethical challenges faced by TEC and encourage further discussion around this topic. (PsycINFO Database Record}, } @article {pmid28724028, year = {2017}, author = {Estrada-Martínez, LM}, title = {Commentary on Chavez-Ayala et al.'s "Violencia y la Salud Mental Asociados a Pensar o Haber Intentado Emigrar Internacionalmente por Adolescentes Mexicanos".}, journal = {Cadernos de saude publica}, volume = {33}, number = {6}, pages = {e00089317}, doi = {10.1590/0102-311X00089317}, pmid = {28724028}, issn = {1678-4464}, } @article {pmid28719621, year = {2017}, author = {Kang, D and Jung, J and Lee, D and Kim, H and Won, D}, title = {Security analysis and enhanced user authentication in proxy mobile IPv6 networks.}, journal = {PloS one}, volume = {12}, number = {7}, pages = {e0181031}, pmid = {28719621}, issn = {1932-6203}, mesh = {*Cell Phone ; *Computer Security ; }, abstract = {The Proxy Mobile IPv6 (PMIPv6) is a network-based mobility management protocol that allows a Mobile Node(MN) connected to the PMIPv6 domain to move from one network to another without changing the assigned IPv6 address. The user authentication procedure in this protocol is not standardized, but many smartcard based authentication schemes have been proposed. Recently, Alizadeh et al. proposed an authentication scheme for the PMIPv6. However, it could allow an attacker to derive an encryption key that must be securely shared between MN and the Mobile Access Gate(MAG). As a result, outsider adversary can derive MN's identity, password and session key. In this paper, we analyze Alizadeh et al.'s scheme regarding security and propose an enhanced authentication scheme that uses a dynamic identity to satisfy anonymity. Furthermore, we use BAN logic to show that our scheme can successfully generate and communicate with the inter-entity session key.}, } @article {pmid28718978, year = {2017}, author = {Ishizuka, R and Matubayasi, N}, title = {Effective charges of ionic liquid determined self-consistently through combination of molecular dynamics simulation and density-functional theory.}, journal = {Journal of computational chemistry}, volume = {38}, number = {30}, pages = {2559-2569}, doi = {10.1002/jcc.24880}, pmid = {28718978}, issn = {1096-987X}, abstract = {A self-consistent scheme combining the molecular dynamics (MD) simulation and density functional theory (DFT) was recently proposed to incorporate the effects of the charge transfer and polarization of ions into non-poralizable force fields of ionic liquids for improved description of energetics and dynamics. The purpose of the present work is to analyze the detailed setups of the MD/DFT scheme by focusing on how the basis set, exchange-correlation (XC) functional, charge-fitting method or force field for the intramolecular and Lennard-Jones interactions affects the MD/DFT results of 1,3-dimethylimidazolium bis(trifluoromethylsulfonyl) imide ([C1mim][NTf2]) and 1-ethyl-3-methylimidazolium glycinate ([C2mim][Gly]). It was found that the double-zeta valence polarized or larger size of basis set is required for the convergence of the effective charge of the ion. The choice of the XC functional was further not influential as far as the generalized gradient approximation is used. The charge-fitting method and force field govern the accuracy of the MD/DFT scheme, on the other hand. We examined the charge-fitting methods of Blöchl, the iterative Hirshfeld (Hirshfeld-I), and REPEAT in combination with Lopes et al.'s force field and general AMBER force field. There is no single combination of charge fitting and force field that provides good agreements with the experiments, while the MD/DFT scheme reduces the effective charges of the ions and leads to better description of energetics and dynamics compared to the original force field with unit charges. © 2017 Wiley Periodicals, Inc.}, } @article {pmid28717820, year = {2017}, author = {Vibell, J and Klinge, C and Zampini, M and Nobre, AC and Spence, C}, title = {Differences between endogenous attention to spatial locations and sensory modalities.}, journal = {Experimental brain research}, volume = {235}, number = {10}, pages = {2983-2996}, pmid = {28717820}, issn = {1432-1106}, mesh = {Adult ; Attention/*physiology ; Electroencephalography ; Electrooculography ; Evoked Potentials, Visual/*physiology ; Female ; Humans ; Male ; Psychomotor Performance/*physiology ; Space Perception/*physiology ; Touch Perception/*physiology ; Visual Perception/*physiology ; Young Adult ; }, abstract = {Vibell et al. (J Cogn Neurosci 19:109-120, 2007) reported that endogenously attending to a sensory modality (vision or touch) modulated perceptual processing, in part, by the relative speeding-up of neural activation (i.e., as a result of prior entry). However, it was unclear whether it was the fine temporal discrimination required by the temporal-order judgment task that was used, or rather, the type of attentional modulation (spatial locations or sensory modalities) that was responsible for the shift in latencies that they observed. The present study used a similar experimental design to evaluate whether spatial attention would also yield similar latency effects suggestive of prior entry in the early visual P1 potentials. Intriguingly, while the results demonstrate similar neural latency shifts attributable to spatial attention, they started at a somewhat later stage than seen in Vibell et al.'s study. These differences are consistent with different neural mechanisms underlying attention to a specific sensory modality versus to a spatial location.}, } @article {pmid28713322, year = {2017}, author = {Zacher, H and Dirkers, BT and Korek, S and Hughes, B}, title = {Age-Differential Effects of Job Characteristics on Job Attraction: A Policy-Capturing Study.}, journal = {Frontiers in psychology}, volume = {8}, number = {}, pages = {1124}, pmid = {28713322}, issn = {1664-1078}, abstract = {Based on an integration of job design and lifespan developmental theories, Truxillo et al. (2012) proposed that job characteristics interact with employee age in predicting important work outcomes. Using an experimental policy-capturing design, we investigated age-differential effects of four core job characteristics (i.e., job autonomy, task variety, task significance, and feedback from the job) on job attraction (i.e., individuals' rating of job attractiveness). Eighty-two employees between 19 and 65 years (Mage = 41, SD = 14) indicated their job attraction for each of 40 hypothetical job descriptions in which the four job characteristics were systematically manipulated (in total, participants provided 3,280 ratings). Results of multilevel analyses showed that the positive effects of task variety, task significance, and feedback from the job were stronger for younger compared to older employees, whereas we did not find significant age-differential effects of job autonomy on job attraction. These findings are only partially consistent with propositions of Truxillo et al.'s (2012) lifespan perspective on job design.}, } @article {pmid28712010, year = {2018}, author = {Okely, JA and Weiss, A and Gale, CR}, title = {The interaction between individualism and wellbeing in predicting mortality: Survey of Health Ageing and Retirement in Europe.}, journal = {Journal of behavioral medicine}, volume = {41}, number = {1}, pages = {1-11}, pmid = {28712010}, issn = {1573-3521}, support = {MC_UP_A620_1015/MRC_/Medical Research Council/United Kingdom ; MC_U147585827/MRC_/Medical Research Council/United Kingdom ; MC_UU_12011/2/MRC_/Medical Research Council/United Kingdom ; MC_U147585819/MRC_/Medical Research Council/United Kingdom ; MR/K026992/1/MRC_/Medical Research Council/United Kingdom ; MC_UP_A620_1014/MRC_/Medical Research Council/United Kingdom ; MC_UU_12011/1/MRC_/Medical Research Council/United Kingdom ; G0400491/MRC_/Medical Research Council/United Kingdom ; MC_U147585824/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Aged ; Aged, 80 and over ; Aging/*psychology ; Cause of Death ; Chronic Disease/mortality ; Correlation of Data ; Cross-Cultural Comparison ; Europe ; Female ; Health Surveys ; Healthy Aging/*psychology ; Humans ; *Individuality ; Longevity ; Longitudinal Studies ; Male ; Middle Aged ; Proportional Hazards Models ; Prospective Studies ; Quality of Life/*psychology ; Retirement/*psychology ; Risk Factors ; }, abstract = {The link between greater wellbeing and longevity is well documented. The aim of the current study was to test whether this association is consistent across individualistic and collectivistic cultures. The sample consisted of 13,596 participants from 11 European countries, each of which was assigned an individualism score according to Hofstede et al.'s (Cultures and organizations: software of the mind, McGraw Hill, New York, 2010) cultural dimension of individualism. We tested whether individualism moderated the cross-sectional association between wellbeing and self-rated health or the longitudinal association between wellbeing and mortality risk. Our analysis revealed a significant interaction between individualism and wellbeing such that the association between wellbeing and self-rated health or risk of mortality from cardiovascular disease was stronger in more individualistic countries. However, the interaction between wellbeing and individualism was not significant in analysis predicting all-cause mortality. Further prospective studies are needed to confirm our finding and to explore the factors responsible for this culturally dependent effect.}, } @article {pmid28699255, year = {2017}, author = {Hupé, C and Lavallée, A}, title = {Internal and external validity of Chen et al.'s nursing-sensitive quality indicators for the neonatal intensive care unit.}, journal = {Journal of clinical nursing}, volume = {26}, number = {23-24}, pages = {e6-e7}, doi = {10.1111/jocn.13956}, pmid = {28699255}, issn = {1365-2702}, } @article {pmid28698061, year = {2017}, author = {Brits, D and Manger, PR and Bidmos, MA}, title = {The accuracy of the anatomical method for stature estimation in Black South African females.}, journal = {Forensic science international}, volume = {278}, number = {}, pages = {409.e1-409.e10}, doi = {10.1016/j.forsciint.2017.06.004}, pmid = {28698061}, issn = {1872-6283}, mesh = {Adult ; *Black People ; *Body Height ; Bone and Bones/anatomy & histology/*diagnostic imaging ; Female ; Forensic Anthropology/methods ; Humans ; Magnetic Resonance Imaging ; Middle Aged ; Regression Analysis ; South Africa ; Whole Body Imaging ; Young Adult ; }, abstract = {The anatomical method is considered the most accurate stature estimation method, but investigation has shown that it continuously underestimates stature. This underestimation is believed to be related to the use of universal soft tissue correction factors. Therefore, the aim of this study was to assess the accuracy of the soft tissue correction factors in a living population of Black South African females and to subsequently calculate a new soft tissue correction factor, specific for stature estimation in this population group. Thirty Black South African adult females voluntarily participated in this study and underwent a full body Magnetic Resonance Imaging (MRI) scan. Living stature was measured with a stadiometer and total skeletal height (TSH) was calculated from the MRI measurements. Stature was estimated from the TSH of each participant using Fully's (1956) [17], Raxter et al.'s (2006) [38] and Bidmos and Manger's (2012) [5] methods. Results indicated strong, statistically significant positive correlations between living and estimated statures, however, paired t-tests revealed that living stature was significantly underestimated using Fully's and Raxter et al.'s methods, while the method by Bidmos and Manger significantly overestimated stature. A lack of statistically significant correlations between soft tissue correction factors and the total skeletal height was found. Likewise, an absence of statistically significant correlations between age and the estimation error, with and without age adjustments were also observed. A new soft tissue correction factor, specific for stature estimation in Black South African females was calculated. The newly proposed regression equation presented improved stature estimation accuracies for this population group.}, } @article {pmid28690569, year = {2017}, author = {Sullivan, P and Blacker, M}, title = {The Effect of Different Phases of Synchrony on Pain Threshold in a Drumming Task.}, journal = {Frontiers in psychology}, volume = {8}, number = {}, pages = {1034}, pmid = {28690569}, issn = {1664-1078}, abstract = {Behavioral synchrony has been linked to endorphin activity (Cohen et al., 2010; Sullivan and Rickers, 2013; Sullivan et al., 2014; Tarr et al., 2015, 2016; Weinstein et al., 2016). This has been called the synchrony effect. Synchrony has two dominant phases of movement; in-phase and anti-phase. The majority of research investigating synchrony's effect on endorphin activity has focused on in-phase synchrony following vigorous activities. The only research to investigate the effects of anti-phase synchrony on endorphin activity found that anti-phase synchronized rowing did not produce the synchrony effect (Sullivan et al., 2014). Anti-phase synchrony, however, is counter-intuitive to the sport of rowing and may have interfered with the synchrony effect. This study investigated the effect of anti-phase synchrony on endorphin activity in a different task (i.e., drumming). University students (n = 30) were asked to drum solo and in in-phase and anti-phase pairs for 3 min. Pain threshold was assessed as an indirect indicator of endorphin activity prior to and following the task. Although the in-phase synchrony effect was not found, a repeated measures ANOVA found that there was a significant difference in pain threshold change among the three conditions [F(2,24) = 4.10, = 0.255, p < 0.05). Post hoc t-tests showed that the anti-phase condition had a significantly greater pain threshold change than both the solo and in-phase conditions at p < 0.05. This is the first time that anti-phase synchrony has been shown to produce the synchrony effect. Because anti-phase drumming may have required more attention between partners than in-phase synchrony, it may have affected self-other merging (Tarr et al., 2014). These results support Tarr et al.'s (2014) model that multiple mechanisms account for the effect of synchrony on pain threshold, and suggest that different characteristics of the activity may influence the synchrony effect.}, } @article {pmid28685362, year = {2018}, author = {Salama, A and Saafan, T and El Ansari, W and Karam, M and Bashah, M}, title = {Is Routine Preoperative Esophagogastroduodenoscopy Screening Necessary Prior to Laparoscopic Sleeve Gastrectomy? Review of 1555 Cases and Comparison with Current Literature.}, journal = {Obesity surgery}, volume = {28}, number = {1}, pages = {52-60}, pmid = {28685362}, issn = {1708-0428}, mesh = {Adult ; Comorbidity ; Diagnostic Tests, Routine/*methods ; *Endoscopy, Digestive System ; Female ; *Gastrectomy/methods/statistics & numerical data ; Gastroesophageal Reflux/complications/diagnosis/epidemiology/surgery ; Hernia, Hiatal/complications/diagnosis/epidemiology/surgery ; Humans ; Laparoscopy/methods/statistics & numerical data ; Male ; Middle Aged ; Obesity, Morbid/complications/diagnosis/epidemiology/*surgery ; Predictive Value of Tests ; Preoperative Care/*methods ; Retrospective Studies ; Stomach Neoplasms/surgery ; Treatment Outcome ; }, abstract = {BACKGROUND: Controversy exists as to whether routine preoperative esophagogastroduodenoscopy (p-OGD) in bariatric surgery should be routinely undertaken or undertaken selectively based on patients' symptoms. As very few studies have focused on the role of p-OGD prior to the increasingly common laparoscopic sleeve gastrectomy (LSG), we assessed the role/impact of p-OGD in LSG patients.

METHODS: Retrospective review of records of all LSG patients operated upon at Hamad General Hospital, Qatar (2011-2014, n = 1555). All patients were screened by p-OGD. Patient characteristics were analyzed, and p-OGD findings were categorized into four groups employing Sharaf et al.'s classification (Obes Surg 14:1367-1372, 23). We assessed the impact of p-OGD findings on any change in surgical management or lack thereof.

RESULTS: p-OGD findings indicated that 89.5% of our patients had normal or mild findings and were asymptomatic (groups 0 and 1, not necessitating any change in surgical management), and no patients had gastric cancer or varices (group 3). A total of 10.5% of our sample were categorized as group 2 patients who, according to Sharaf et al. (Obes Surg 14:1367-1372, 23), might have their surgical approach changed. All patients diagnosed preoperatively with hiatal hernia (HH) had LSG with crural repair and their symptoms resolved postoperatively.

CONCLUSION: Due to effectiveness and best utilization of resources, routine p-OGD screening in patients scheduled for LSG may require further justification for asymptomatic patients especially in regions with low upper GI cancers. p-OGD findings had low impact on the management of asymptomatic patients. Crural repair plus LSG was effective for hiatal hernia.}, } @article {pmid28674643, year = {2017}, author = {Dai, L and Kou, H and Xia, Y and Wen, X and Gao, J and Ma, ZS}, title = {Does colorectal cancer significantly influence the assembly of gut microbial communities?.}, journal = {PeerJ}, volume = {5}, number = {}, pages = {e3383}, pmid = {28674643}, issn = {2167-8359}, abstract = {Colorectal cancer (CRC) is the third commonest malignant tumor. Previous studies have revealed that the composition change of the human gut microbiome, measured by community diversity, is associated with the progression of CRC. However, a further question, whether or not the mechanism of community assembly and diversity maintenance of the gut microbiome is influenced by CRC has not been addressed. To address this question, we applied Hubbell's neutral theory for biodiversity to reanalyze the dataset from Wang et al.'s (2012) study of the gut microbiome sampled from 46 CRC patients and 56 healthy individuals. Our reanalysis presents two important findings. Firstly, our analysis demonstrated that only around 4% (4/102) samples (in total of both the CRC and control groups) have their species abundance distribution (SAD) satisfied the prediction of the neutral theory null model. No significant difference in the number of the samples satisfying the neutral null model was detected between the healthy individuals and CRC patients, suggesting that the nature or mechanism of community assembly and diversity maintenance of the gut microbiome is not significantly influenced by CRC. That is, the stochasticity of survival, reproduction and migration of gut microbes, as implied by the neutral theory model, does not play a significant role in shaping the community assembly and diversity maintenance. We further infer that the alternative hypothesis to the neutral null model, i.e., the deterministic niche differentiations should be the driving forces that shape the assembly and diversity maintenance of the gut microbiome in both the healthy individuals and CRC patients. Secondly, although CRC does not seem to influence the nature of community assembly, we postulate that it may indirectly influence the outcome (i.e., the community composition as measured by community diversity) of the community assembly, possibly by influencing niche differentiations. This postulation is supported by our second finding: the diversity of the gut microbiome in CRC patients is significantly lower than that in the healthy individuals as demonstrated by the fundamental diversity parameter (θ) of the neutral theory model. This second finding offers an independent confirmation of the relationship between the CRC disease and diversity of the gut microbiome, about which existing studies have presented conflicting evidences. Finally, we suggest that hybrid modeling which integrates both the neutral and niche theories should be explored in future studies to further understanding of the CRC influence on the human gut microbiome.}, } @article {pmid28673036, year = {2017}, author = {Keyes, KM and Tracy, M and Mooney, SJ and Shev, A and Cerdá, M}, title = {Invited Commentary: Agent-Based Models-Bias in the Face of Discovery.}, journal = {American journal of epidemiology}, volume = {186}, number = {2}, pages = {146-148}, pmid = {28673036}, issn = {1476-6256}, support = {K01 DA030449/DA/NIDA NIH HHS/United States ; R21 AA021909/AA/NIAAA NIH HHS/United States ; R21 DA041154/DA/NIDA NIH HHS/United States ; T32 HD057822/HD/NICHD NIH HHS/United States ; }, mesh = {*Bias ; Humans ; *Population Dynamics ; }, abstract = {Agent-based models (ABMs) have grown in popularity in epidemiologic applications, but the assumptions necessary for valid inference have only partially been articulated. In this issue, Murray et al. (Am J Epidemiol. 2017;186(2):131-142) provided a much-needed analysis of the consequence of some of these assumptions, comparing analysis using an ABM to a similar analysis using the parametric g-formula. In particular, their work focused on the biases that can arise in ABMs that use parameters drawn from distinct populations whose causal structures and baseline outcome risks differ. This demonstration of the quantitative issues that arise in transporting effects between populations has implications not only for ABMs but for all epidemiologic applications, because making use of epidemiologic results requires application beyond a study sample. Broadly, because health arises within complex, dynamic, and hierarchical systems, many research questions cannot be answered statistically without strong assumptions. It will require every tool in our store of methods to properly understand population dynamics if we wish to build an evidence base that is adequate for action. Murray et al.'s results provide insight into these assumptions that epidemiologists can use when selecting a modeling approach.}, } @article {pmid28672169, year = {2017}, author = {Felton, A and Wright, N}, title = {Simulation in mental health nurse education: The development, implementation and evaluation of an educational innovation.}, journal = {Nurse education in practice}, volume = {26}, number = {}, pages = {46-52}, doi = {10.1016/j.nepr.2017.06.005}, pmid = {28672169}, issn = {1873-5223}, mesh = {Clinical Competence/standards ; Education, Nursing, Baccalaureate/methods/standards ; Humans ; *Patient Simulation ; Problem-Based Learning/methods ; Psychiatric Nursing/*education ; Qualitative Research ; Self Efficacy ; Students, Nursing/*psychology ; Surveys and Questionnaires ; United Kingdom ; }, abstract = {Simulation is an important learning approach for the development of skills for healthcare practice. However, it remains under used in the education of mental health practitioners. This article examines the development, implementation and evaluation of a simulated learning experience for final year undergraduate BSc mental health nursing students in the UK. Scenarios involving managing care in an acute in patient ward and community older persons' team were designed to enable students to develop their complex decision making skills. An evaluation of the simulation experience was undertaken. This was informed by the principles of improvement science methodology and data was collected from the student participants using questionnaires. The findings indicated that simulation provided a realistic environment in which students were able to develop skills and manage clinical situations autonomously without fear of being assessed or making mistakes. Reflecting Dieckmann et al.'s (2007) position that simulation is a social situation in itself, the learning approach enabled mental health students to both experience the safety of the Higher Education setting and also the reality of clinical practice. Simulation may therefore provide an important tool to prepare students for the responsibilities of a qualified nurse.}, } @article {pmid28657220, year = {2017}, author = {Lora, D and Gómez de la Cámara, A and Fernández, SP and Enríquez de Salamanca, R and Gómez, JFPR}, title = {Prognostic models for locally advanced cervical cancer: external validation of the published models.}, journal = {Journal of gynecologic oncology}, volume = {28}, number = {5}, pages = {e58}, pmid = {28657220}, issn = {2005-0399}, mesh = {Adult ; Aged ; Aged, 80 and over ; Area Under Curve ; Chemoradiotherapy ; Cohort Studies ; Disease-Free Survival ; Female ; Humans ; Middle Aged ; Neoplasm Recurrence, Local/epidemiology ; Prognosis ; Proportional Hazards Models ; ROC Curve ; Risk ; Spain ; Treatment Outcome ; Uterine Cervical Neoplasms/*diagnosis/*mortality/therapy ; }, abstract = {OBJECTIVE: To externally validate the prognostic models for predicting the time-dependent outcome in patients with locally advanced cervical cancer (LACC) who were treated with concurrent chemoradiotherapy in an independent cohort.

METHODS: A historical cohort of 297 women with LACC who were treated with radical concurrent chemoradiotherapy from 1999 to 2014 at the 12 de Octubre University Hospital (H12O), Madrid, Spain. The external validity of prognostic models was quantified regarding discrimination, calibration, measures of overall performance, and decision curve analyses.

RESULTS: The review identified 8 studies containing 13 prognostic models. Different (International Federation of Gynecology and Obstetrics [FIGO] stages, parametrium involvement, hydronephrosis, location of positive nodes, and race) but related cohorts with validation cohort (5-year overall survival [OS]=70%; 5-year disease-free survival [DFS]=64%; average age of 50; and over 79% squamous cell) were evaluated. The following models exhibited good external validity in terms of discrimination and calibration but limited clinical utility: the OS model at 3 year from Kidd et al.'s study (area under the receiver operating characteristic curve [AUROC]=0.69; threshold of clinical utility [TCU] between 36% and 50%), the models of DFS at 1 year from Kidd et al.'s study (AUROC=0.64; TCU between 24% and 32%) and 2 years from Rose et al.'s study (AUROC=0.70; TCU between 19% and 58%) and the distant recurrence model at 5 years from Kang et al.'s study (AUROC=0.67; TCU between 12% and 36%).

CONCLUSION: The external validation revealed the statistical and clinical usefulness of 4 prognostic models published in the literature.}, } @article {pmid28648237, year = {2017}, author = {Sarkar, M and Fletcher, D}, title = {Adversity-related experiences are essential for Olympic success: Additional evidence and considerations.}, journal = {Progress in brain research}, volume = {232}, number = {}, pages = {159-165}, doi = {10.1016/bs.pbr.2016.11.009}, pmid = {28648237}, issn = {1875-7855}, mesh = {Athletes/*psychology ; *Competitive Behavior ; Humans ; Sports/*psychology ; *Stress, Psychological ; }, abstract = {Drawing on Hardy et al.'s study as the target article, in this commentary, we focus on the adversity-related experiences and consequences of the Olympic and/or World champions that they sampled. With this in mind, we divide the narrative into two main sections. In the first section, we explore the association between adversity-related experiences and Olympic success, and provide additional evidence in support of the notion that adversity-related experiences are essential for success at the highest level of sport. In the second section, we discuss the role of adversity-related experiences in Olympic success considering a series of important psychosocial processes that are required for superior performance. In ending, we reflect on the salient (contentious and ethical) issues in the study and practice of adversity-related experiences and sport performance. We hope that our commentary adds to the extant literature and is useful for future study and practice in performance sport.}, } @article {pmid28648231, year = {2017}, author = {Baker, J}, title = {The journey of a thousand miles…: Notes on Hardy et al.'s Great British Medalists Project.}, journal = {Progress in brain research}, volume = {232}, number = {}, pages = {133-136}, doi = {10.1016/bs.pbr.2016.12.001}, pmid = {28648231}, issn = {1875-7855}, mesh = {Athletes/*psychology ; Humans ; Sports/*psychology ; United Kingdom ; }, abstract = {The Great British Medalist Project is an exceptional project that is destined to generate much discussion among researchers in psychology, skill acquisition, and expertise. The authors should be congratulated for a project of incredible growth and scope. This brief commentary highlights a range of interesting findings, some novel and some supportive of previous research, but urges caution until their validity, reliability, and generalizability can be determined. Several directions for further research are also briefly discussed.}, } @article {pmid28648229, year = {2017}, author = {Howle, TC and Eklund, RC}, title = {On elite and super-elite Great British athletes: Some theoretical implications from findings.}, journal = {Progress in brain research}, volume = {232}, number = {}, pages = {121-125}, doi = {10.1016/bs.pbr.2017.02.001}, pmid = {28648229}, issn = {1875-7855}, mesh = {Athletes/*psychology ; Competitive Behavior ; Humans ; *Motivation ; Personality ; Sports/*psychology ; United Kingdom ; }, abstract = {We present commentary focused on the theoretical implications of Hardy et al.'s (2017) study of elite (E) and super-elite (SE) UK athletes. Athlete developmental experiences are first discussed, and we consider how Hardy et al.'s findings fit with extant and emerging theory regarding motivation and experiences of adversity. We then focus on athlete characteristics and propose a complementary theory-based interpretation of Hardy et al.'s findings based on the idea that SE athletes may be more focused on agency than E athletes. We consider this proposition in light of theory and empirical research addressing the agency and communion theoretical distinction.}, } @article {pmid28644827, year = {2017}, author = {Koenig, WD}, title = {What drives cooperative breeding?.}, journal = {PLoS biology}, volume = {15}, number = {6}, pages = {e2002965}, pmid = {28644827}, issn = {1545-7885}, mesh = {Animals ; Animals, Wild/*physiology ; *Behavior, Animal ; Biological Evolution ; Birds ; *Breeding ; Climatic Processes ; Ecosystem ; Extreme Environments ; Female ; Male ; *Nesting Behavior ; Phylogeny ; *Social Behavior ; Species Specificity ; }, abstract = {Cooperative breeding, in which more than a pair of conspecifics cooperate to raise young at a single nest or brood, is widespread among vertebrates but highly variable in its geographic distribution. Particularly vexing has been identifying the ecological correlates of this phenomenon, which has been suggested to be favored in populations inhabiting both relatively stable, productive environments and in populations living under highly variable and unpredictable conditions. Griesser et al. provide a novel approach to this problem, performing a phylogenetic analysis indicating that family living is an intermediate step between nonsocial and cooperative breeding birds. They then examine the ecological and climatic conditions associated with these different social systems, concluding that cooperative breeding emerges when family living is favored in highly productive environments, followed secondarily by selection for cooperative breeding when environmental conditions deteriorate and within-year variability increases. Combined with recent work addressing the fitness consequences of cooperative breeding, Griesser et al.'s contribution stands to move the field forward by demonstrating that the evolution of complex adaptations such as cooperative breeding may only be understood when each of the steps leading to it are identified and carefully integrated.}, } @article {pmid28639806, year = {2017}, author = {Lauermann, F and Tsai, YM and Eccles, JS}, title = {Math-related career aspirations and choices within Eccles et al.'s expectancy-value theory of achievement-related behaviors.}, journal = {Developmental psychology}, volume = {53}, number = {8}, pages = {1540-1559}, doi = {10.1037/dev0000367}, pmid = {28639806}, issn = {1939-0599}, mesh = {*Achievement ; Adolescent ; Adult ; *Aspirations, Psychological ; Attitude ; *Career Choice ; Child ; Cognition/physiology ; Cohort Studies ; Female ; Humans ; Male ; Mathematics/*education ; *Models, Psychological ; Motivation/*physiology ; Parent-Child Relations ; Self Report ; Sex Characteristics ; }, abstract = {Which occupation to pursue is one of the more consequential decisions people make and represents a key developmental task. Yet the underlying developmental processes associated with either individual or group differences in occupational choices are still not well understood. This study contributes toward filling this gap, focusing in particular on the math domain. We examined two aspects of Eccles et al.'s (1983) expectancy-value theory of achievement-related behaviors: (a) the reciprocal associations between adolescents' expectancy and subjective task value beliefs and adolescents' career plans and (b) the multiplicative association between expectancies and values in predicting occupational outcomes in the math domain. Our analyses indicate that adolescents' expectancy and subjective task value beliefs about math and their math- or science-related career plans reported at the beginning and end of high school predict each other over time, with the exception of intrinsic interest in math. Furthermore, multiplicative associations between adolescents' expectancy and subjective task value beliefs about math predict math-related career attainment approximately 15 years after graduation from high school. Gender differences emerged regarding career-related beliefs and career attainment, with male students being more likely than female to both pursue and attain math-related careers. These gender differences could not be explained by differences in beliefs about math as an academic subject. (PsycINFO Database Record}, } @article {pmid28637261, year = {2017}, author = {Moyers, BA and Zhang, J}, title = {Further Simulations and Analyses Demonstrate Open Problems of Phylostratigraphy.}, journal = {Genome biology and evolution}, volume = {9}, number = {6}, pages = {1519-1527}, pmid = {28637261}, issn = {1759-6653}, support = {R01 GM120093/GM/NIGMS NIH HHS/United States ; T32 HG000040/HG/NHGRI NIH HHS/United States ; }, mesh = {Computer Simulation ; *Evolution, Molecular ; Genomics/*methods/standards ; Humans ; Models, Genetic ; *Phylogeny ; }, abstract = {Phylostratigraphy, originally designed for gene age estimation by BLAST-based protein homology searches of sequenced genomes, has been widely used for studying patterns and inferring mechanisms of gene origination and evolution. We previously showed by computer simulation that phylostratigraphy underestimates gene age for a nonnegligible fraction of genes and that the underestimation is severer for genes with certain properties such as fast evolution and short protein sequences. Consequently, many previously reported age distributions of gene properties may have been methodological artifacts rather than biological realities. Domazet-Lošo and colleagues recently argued that our simulations were flawed and that phylostratigraphic bias does not impact inferences about gene emergence and evolution. Here we discuss conceptual difficulties of phylostratigraphy, identify numerous problems in Domazet-Lošo et al.'s argument, reconfirm phylostratigraphic error using simulations suggested by Domazet-Lošo and colleagues, and demonstrate that a phylostratigraphic trend claimed to be robust to error disappears when genes likely to be error-resistant are analyzed. We conclude that extreme caution is needed in interpreting phylostratigraphic results because of the inherent biases of the method and that reanalysis using genes exhibiting no error in realistic simulations may help reduce spurious findings.}, } @article {pmid28628806, year = {2017}, author = {Ozawa, C and Suzuki, T and Mizuno, Y and Tarumi, R and Yoshida, K and Fujii, K and Hirano, J and Tani, H and Rubinstein, EB and Mimura, M and Uchida, H}, title = {Resilience and spirituality in patients with depression and their family members: A cross-sectional study.}, journal = {Comprehensive psychiatry}, volume = {77}, number = {}, pages = {53-59}, doi = {10.1016/j.comppsych.2017.06.002}, pmid = {28628806}, issn = {1532-8384}, mesh = {Adult ; Cross-Sectional Studies ; Depressive Disorder/*psychology ; Family/*psychology ; Female ; Humans ; Japan ; Male ; Middle Aged ; Outpatients/psychology ; Religion and Psychology ; *Resilience, Psychological ; Self Concept ; *Spirituality ; }, abstract = {OBJECTIVE: The degree and quality of resilience in patients with depression have never been investigated in the context of remission status, spirituality/religiosity, and family members' resilience levels, which was addressed in this study.

METHODS: This cross-sectional study recruited Japanese outpatients with depressive disorder according to ICD-10 and cohabitant family members who were free from psychiatric diagnoses. Resilience was assessed using the 25-item Resilience Scale (RS). Other assessments included the Montgomery-Asberg Depression Rating Scale (MADRS); the Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being Scale (FACIT) and Kasen et al.'s (2012) scale for spirituality/religiosity; and the Rosenberg Self-Esteem Scale (RSES).

RESULTS: One hundred outpatients with depression (mean±SD age, 50.8±14.5years; 44 men; MADRS total score 9.8±9.0) and 36 healthy family members (mean±SD age, 56.5±15.0years; 18 men) were included. Symptom severity, attendance at religious/spiritual services, and self-esteem were significantly associated with RS scores in the patient group. RS total scores were significantly higher in remitted patients compared to non-remitted patients (mean±SD, 112.3±17.1 vs. 84.8±27.7, p<0.001). No correlation was found in RS total scores between patients and their family members (p=0.265), regardless of patients' remission status.

CONCLUSIONS: Resilience may be influenced by individual characteristics rather than familial environment; furthermore, self-esteem or spirituality/religiosity may represent reinforcing elements. While caution is necessary in extrapolating these findings to other patient populations, our results suggest that resilience may be considered a state marker in depression.}, } @article {pmid28617229, year = {2017}, author = {Heo, GE and Kang, KY and Song, M and Lee, JH}, title = {Analyzing the field of bioinformatics with the multi-faceted topic modeling technique.}, journal = {BMC bioinformatics}, volume = {18}, number = {Suppl 7}, pages = {251}, pmid = {28617229}, issn = {1471-2105}, mesh = {Bibliometrics ; Computational Biology/*methods ; Data Mining ; Databases, Factual ; Humans ; *Models, Theoretical ; }, abstract = {BACKGROUND: Bioinformatics is an interdisciplinary field at the intersection of molecular biology and computing technology. To characterize the field as convergent domain, researchers have used bibliometrics, augmented with text-mining techniques for content analysis. In previous studies, Latent Dirichlet Allocation (LDA) was the most representative topic modeling technique for identifying topic structure of subject areas. However, as opposed to revealing the topic structure in relation to metadata such as authors, publication date, and journals, LDA only displays the simple topic structure.

METHODS: In this paper, we adopt the Tang et al.'s Author-Conference-Topic (ACT) model to study the field of bioinformatics from the perspective of keyphrases, authors, and journals. The ACT model is capable of incorporating the paper, author, and conference into the topic distribution simultaneously. To obtain more meaningful results, we use journals and keyphrases instead of conferences and bag-of-words.. For analysis, we use PubMed to collected forty-six bioinformatics journals from the MEDLINE database. We conducted time series topic analysis over four periods from 1996 to 2015 to further examine the interdisciplinary nature of bioinformatics.

RESULTS: We analyze the ACT Model results in each period. Additionally, for further integrated analysis, we conduct a time series analysis among the top-ranked keyphrases, journals, and authors according to their frequency. We also examine the patterns in the top journals by simultaneously identifying the topical probability in each period, as well as the top authors and keyphrases. The results indicate that in recent years diversified topics have become more prevalent and convergent topics have become more clearly represented.

CONCLUSION: The results of our analysis implies that overtime the field of bioinformatics becomes more interdisciplinary where there is a steady increase in peripheral fields such as conceptual, mathematical, and system biology. These results are confirmed by integrated analysis of topic distribution as well as top ranked keyphrases, authors, and journals.}, } @article {pmid28612191, year = {2017}, author = {Ko, S and Choi, W and Chae, S}, title = {Comparison of inter- and intra-observer reliability among the three classification systems for cervical spinal canal stenosis.}, journal = {European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society}, volume = {26}, number = {9}, pages = {2290-2296}, pmid = {28612191}, issn = {1432-0932}, mesh = {Adult ; Aged ; Aged, 80 and over ; Constriction, Pathologic/classification ; Female ; Humans ; Magnetic Resonance Imaging/methods ; Male ; Middle Aged ; Observer Variation ; Reproducibility of Results ; Retrospective Studies ; Spinal Canal/*pathology ; Spinal Stenosis/*classification/pathology ; Young Adult ; }, abstract = {PURPOSE: The aim is to analyze the agreement between different types of physicians in terms of the inter-observer and intra-observer reliability in addition to the agreement between the experienced and non-experienced physicians with respect to three different classification systems for diagnosis of cervical spinal canal stenosis.

METHODS: Total nine doctors including experienced group of three doctors and non-experienced group of six doctors classified the patients according to three different classification in an independent, blinded manner using magnetic resonance imaging (MRI) to diagnose cervical canal stenosis. MRI slice included sagittal plane (midline cut) and an image slice from each horizontal plane that penetrated the right center of each disk (C3-4, C4-5, C5-6, and C6-7) was made by PPT format.

RESULTS: For the inter-observer reliability, Vaccaro et al.'s classification system showed the excellent reproducibility, followed by Muhle et al. and Kang et al. All three classification systems showed excellent reproducibility and substantial agreement in terms of the intra-observer reliability.

CONCLUSIONS: All three classification systems showed excellent reproducibility and also displayed a substantial agreement. The classification system used by Vaccaro et al. was proven to be a method with substantial agreement both in the experienced group and the non-experienced group. It can be a useful classification system for simplifying communication among all physicians.}, } @article {pmid28600715, year = {2018}, author = {Reichelson, S and Zax, A and Bass, I and Patalano, AL and Barth, HC}, title = {Partition dependence in consumer choice: Perceptual groupings do not reliably shape decisions.}, journal = {Psychonomic bulletin & review}, volume = {25}, number = {3}, pages = {1178-1183}, pmid = {28600715}, issn = {1531-5320}, support = {1561214//Division of Research on Learning in Formal and Informal Settings/International ; }, mesh = {Adult ; Child ; Child Behavior/*physiology ; Choice Behavior/*physiology ; *Consumer Behavior ; Female ; Humans ; Male ; Young Adult ; }, abstract = {The partitioning of options into arbitrary categories has been shown to influence decisions about allocating choices or resources among those options; this phenomenon is called partition dependence. While we do not call into question the validity of the partition dependence phenomenon in the present work, we do examine the robustness of one of the experimental paradigms reported by Fox, Ratner, and Lieb (Journal of Experimental Psychology: General, 134, 538-551, 2005, Study 4). In three experiments (N = 300) conducted here, participants chose from a menu of perceptually partitioned options (varieties of candy distributed across bowls). We found no clear evidence of partition dependent choice in children (Experiment 1) and no evidence at all of partition dependence in adults' choices (Experiments 1-3). This was true even when methods were closely matched to those of Fox et al.'s Study 4 (Experiment 3). We conclude that the candy-bowl choice task does not reliably elicit partition dependence and propose possible explanations for the discrepancy between these findings and prior reports. Future work will explore the conditions under which partition dependence in consumer choice does reliably arise.}, } @article {pmid28575922, year = {2017}, author = {Racil, G and Lemaire, C and Dubart, AE and Debeaumont, D and Castres, I and Coquart, JB}, title = {Comparison of Specific Prediction Equations to Estimate Peak Oxygen Uptake in Obese Women.}, journal = {International journal of sports medicine}, volume = {38}, number = {7}, pages = {541-545}, doi = {10.1055/s-0042-119726}, pmid = {28575922}, issn = {1439-3964}, mesh = {Adult ; *Exercise Test ; Female ; Humans ; Middle Aged ; Obesity/*physiopathology ; *Oxygen Consumption ; }, abstract = {The aim of the current study was to compare 2 equations to predict peak oxygen uptake (V̇O2peak) in obese women, according to their obesity class. 92 maximal cardiopulmonary exercise testing sets (CPET with initial and subsequent increments set to achieve an exercise duration between 8-12 min) were retrospectively analysed. These CPET were divided into 3 groups according to the women body mass indexes (BMI): class 1 (30 kg.m[-2]≤BMI<35 kg.m[-2], n=22), class 2 (35 kg.m[-2]≤BMI<40 kg.m[-2], n=36) or class 3 (BMI≥40 kg.m[-2], n=34). Each participant's V̇O2peak was predicted from 2 prediction equations (from Wasserman et al.'s and Debeaumont et al.'s equations) and compared with the actual V̇O2peak. Moreover, the correlations between these values were studied, and the accuracy of the predictions was analysed. Only predicted V̇O2peak from the Debeaumont et al.'s equation was not significantly different from the actual V̇O2peak in the women in obesity class 3 (p=0.89). Moreover, significant correlation was found between these values (p<0.001, r=0.68). The bias and the 95% limits of agreement represented -3.2±34.0%. In women in obesity class 3, Debeaumont et al.'s equation may be the accurate one to predict V̇O2peak. However, the accuracy of predictions is low. Consequently, to improve this accuracy, new prediction equations for obese women are required according to the obesity class.}, } @article {pmid28573758, year = {2017}, author = {Marroquin Penaloza, TY and Karkhanis, S and Kvaal, SI and Vasudavan, S and Castelblanco, E and Kruger, E and Tennant, M}, title = {Orthodontic Treatment: Real Risk for Dental Age Estimation in Adults?.}, journal = {Journal of forensic sciences}, volume = {62}, number = {4}, pages = {907-910}, doi = {10.1111/1556-4029.13371}, pmid = {28573758}, issn = {1556-4029}, mesh = {Adolescent ; Adult ; Age Determination by Teeth/*methods ; Female ; Humans ; Image Interpretation, Computer-Assisted ; Male ; Middle Aged ; *Orthodontic Appliances ; *Radiography, Panoramic ; Young Adult ; }, abstract = {Dental age estimation becomes a challenge once the root formation is concluded. In living adults, one dental age indicator is the formation of secondary dentine, also associated with orthodontic treatment as well as root shortening. The aim of this study was to establish whether these secondary effects of orthodontic treatment could generate a statistically significant difference in dental age estimations when using Kvaal's method. The study sample included 34 pairs of pre- and postorthodontic panoramic radiographs, from different individuals with exactly the same age and sex distribution. Females 65%, median age 17.5 years, and males 35%, median age 22.5 years, were included. After data collection, dental age was estimated per tooth using formulae previously published. The risk of obtaining over-estimation of age was calculated. (RR = 1.007). The changes caused by orthodontic treatment do not have any significant effect on age estimation when Kvaal et al.'s method is applied on panoramic radiographs.}, } @article {pmid28573713, year = {2017}, author = {Gomes-Ng, S and Elliffe, D and Cowie, S}, title = {How do reinforcers affect choice? Preference pulses after responses and reinforcers.}, journal = {Journal of the experimental analysis of behavior}, volume = {108}, number = {1}, pages = {17-38}, doi = {10.1002/jeab.260}, pmid = {28573713}, issn = {1938-3711}, mesh = {Animals ; *Choice Behavior ; Columbidae ; Conditioning, Operant ; *Reinforcement, Psychology ; Time Factors ; }, abstract = {In concurrent schedules, reinforcers are often followed by a brief period of heightened preference for the just-productive alternative. Such 'preference pulses' may reflect local effects of reinforcers on choice. However, similar pulses may occur after nonreinforced responses, suggesting that pulses after reinforcers are partly unrelated to reinforcer effects. McLean, Grace, Pitts, and Hughes (2014) recommended subtracting preference pulses after responses from preference pulses after reinforcers, to construct residual pulses that represent only reinforcer effects. Thus, a reanalysis of existing choice data is necessary to determine whether changes in choice after reinforcers in previous experiments were actually related to reinforcers. In the present paper, we reanalyzed data from choice experiments in which reinforcers served different functions. We compared local choice, mean visit length, and visit-length distributions after reinforcers and after nonreinforced responses. Our reanalysis demonstrated the utility of McLean et al.'s preference-pulse correction for determining the effects of reinforcers on choice. However, visit analyses revealed that residual pulses may not accurately represent reinforcer effects, and reinforcer effects were clearer in visit analyses than in local-choice analyses. The best way to determine the effects of reinforcers on choice may be to conduct visit analyses in addition to local-choice analyses.}, } @article {pmid28556274, year = {2017}, author = {Parish, WJ and Aldridge, A and Allaire, B and Ekwueme, DU and Poehler, D and Guy, GP and Thomas, CC and Trogdon, JG}, title = {A new methodological approach to adjust alcohol exposure distributions to improve the estimation of alcohol-attributable fractions.}, journal = {Addiction (Abingdon, England)}, volume = {112}, number = {11}, pages = {2053-2063}, pmid = {28556274}, issn = {1360-0443}, support = {CC999999/ImCDC/Intramural CDC HHS/United States ; P50 AA005595/AA/NIAAA NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Alcohol Drinking/*epidemiology ; Alcohol-Related Disorders/*epidemiology ; Breast Neoplasms/*epidemiology ; Causality ; Female ; Humans ; *Models, Statistical ; Risk Factors ; Young Adult ; }, abstract = {BACKGROUND AND AIMS: To assess the burden of excessive alcohol use, researchers estimate alcohol-attributable fractions (AAFs) routinely. However, under-reporting in survey data can bias these estimates. We present an approach that adjusts for under-reporting in the estimation of AAFs, particularly within subgroups. This framework is a refinement of a previous method conducted by Rehm et al.

METHODS: We use a measurement error model to derive the 'true' alcohol distribution from a 'reported' alcohol distribution. The 'true' distribution leverages per-capita sales data to identify the distribution average and then identifies the shape of the distribution with self-reported survey data. Data are from the National Alcohol Survey (NAS), the National Household Survey on Drug Abuse (NHSDA) and the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC). We compared our approach with previous approaches by estimating the AAF of female breast cancer cases.

RESULTS: Compared with Rehm et al.'s approach, our refinement performs similarly under a gamma assumption. For example, among females aged 18-25 years, the two approaches produce estimates from NHSDA that are within a percentage point. However, relaxing the gamma assumption generally produces more conservative evidence. For example, among females aged 18-25 years, estimates from NHSDA based on the best-fitting distribution are only 19.33% of breast cancer cases, which is a much smaller proportion than the gamma-based estimates of approximately 28%.

CONCLUSIONS: A refinement of Rehm et al.'s approach to adjusting for underreporting in the estimation of alcohol-attributable fractions provides more flexibility. This flexibility can avoid biases associated with failing to account for the underlying differences in alcohol consumption patterns across different study populations. Comparisons of our refinement with Rehm et al.'s approach show that results are similar when a gamma distribution is assumed. However, results are appreciably lower when the best-fitting distribution is chosen versus gamma-based results.}, } @article {pmid28553237, year = {2017}, author = {Walsh, RS and Muldoon, OT and Fortune, DG and Gallagher, S}, title = {A Longitudinal Study of Relationships between Identity Continuity and Anxiety Following Brain Injury.}, journal = {Frontiers in psychology}, volume = {8}, number = {}, pages = {648}, pmid = {28553237}, issn = {1664-1078}, abstract = {Objective: Anxiety is of particular importance following acquired brain injury (ABI), because anxiety has been identified as a significant predictor of functional outcomes. Continuity of self has been linked to post ABI adjustment and research has linked self-discrepancy to anxiety. This longitudinal study investigates the impact of affiliative and 'self as doer' self-categorisations anxiety. Materials and Methods: Data was collected at two time points. Fifty-three adult ABI survivors participating in post-acute community neuro-rehabilitation participated at time one and 32 of these participated at time two. Participants completed a 28-item identity questionnaire based on Leach et al.'s (2008) multicomponent model of ingroup identification which measured the strength of affiliative and self as doer identities. Anxiety was measured using the Hospital Anxiety and Depression Scale. Results: Analysis indicates a significant mediated relationship between affiliative identification and anxiety via self as doer identification. Contrary to initial prediction, this relationship was significant for those with consistency in affiliative self-categorisation and inconsistency in 'self as doer' self-categorisation. Conclusion: These findings can be interpreted as evidencing the importance of identity continuity and multiplicity following ABI and contribute to the understanding of these through the use of a social identity approach.}, } @article {pmid28552293, year = {2017}, author = {Acabchuk, RL and Kamath, J and Salamone, JD and Johnson, BT}, title = {Stress and chronic illness: The inflammatory pathway.}, journal = {Social science & medicine (1982)}, volume = {185}, number = {}, pages = {166-170}, pmid = {28552293}, issn = {1873-5347}, support = {U24 AG052175/AG/NIA NIH HHS/United States ; }, mesh = {*Antiviral Agents ; Chronic Disease ; Humans ; *Social Class ; }, abstract = {Recent studies have provided important insight into how immune system responses mediate the effects of social adversity and age on chronic illness. Simons et al.’s (2017) ITACT Ratio is a novel assessment of immune functioning that helps expand the toolkit of health psychology. Not only is this study noteworthy in showing how socioeconomic disadvantage may influence immune cell profile, but also it may prompt future work in other domains to use this new index of inflammatory dominance, the ITACT Ratio. This demonstration that social adversity gets “under the skin” through the immune system has much potential for expansion: combining ITACT with other common markers for stress and inflammation, including additional measurements for perceived stress, and expanding the investigation of the link between ITACT and chronic disease in additional populations. Results of future studies will determine if ITACT will emerge as an important new biomarker tying inflammatory dominance to chronic disease.}, } @article {pmid28550946, year = {2017}, author = {Filogonio, R and Costa Leite, CA and Wang, T}, title = {Reply to the commentary by Hillman et al. on: "Vascular distensibilities have minor effects on intracardiac shunt patterns in reptiles" by Filogonio et al. (2017).}, journal = {Zoology (Jena, Germany)}, volume = {122}, number = {}, pages = {55-57}, doi = {10.1016/j.zool.2017.05.005}, pmid = {28550946}, issn = {1873-2720}, mesh = {Animals ; Cardiac Output ; *Heart ; *Reptiles ; Snakes ; Turtles ; }, abstract = {Our meta-analysis (Filogonio et al., 2017) on central vascular blood flows in a snake (Crotalus durissus) and a turtle (Trachemys scripta) was motivated by Hillman et al.'s (2014) analysis on amphibians to investigate whether cardiac shunt patterns depend on cardiac output and vascular distensibilities. In contrast to Hillman et al. (2014), we did not uncover a general trend that supports the notion that cardiac shunts in reptiles are dictated by vascular distensibilities. In addition to our response to the criticism raised by Hillman et al. (2017), we suggest that future experiments should consider (i) both compliance and distensibility of the major arteries; (ii) differences in volume of the systemic and pulmonary circuits to account for the accommodation of stroke volume; and (iii) an evaluation of the pulsatile pressures in both the ventricle and the major arteries to consider the timing of the ventricular ejection provided by opening of the ventricular valves. We hope these suggestions may help future clarification of the relative importance of passive arterial mechanical properties compared to autonomic regulation in determining intracardiac shunts in both amphibians and reptiles.}, } @article {pmid28547680, year = {2017}, author = {Kunar, MA and Watson, DG and Tsetsos, K and Chater, N}, title = {The influence of attention on value integration.}, journal = {Attention, perception & psychophysics}, volume = {79}, number = {6}, pages = {1615-1627}, pmid = {28547680}, issn = {1943-393X}, mesh = {Adolescent ; Attention/*physiology ; Decision Making/*physiology ; Female ; Humans ; Judgment/*physiology ; Male ; *Social Values ; Young Adult ; }, abstract = {People often have to make decisions based on many pieces of information. Previous work has found that people are able to integrate values presented in a rapid serial visual presentation (RSVP) stream to make informed judgements on the overall stream value (Tsetsos et al. Proceedings of the National Academy of Sciences of the United States of America, 109(24), 9659-9664, 2012). It is also well known that attentional mechanisms influence how people process information. However, it is unknown how attentional factors impact value judgements of integrated material. The current study is the first of its kind to investigate whether value judgements are influenced by attentional processes when assimilating information. Experiments 1-3 examined whether the attentional salience of an item within an RSVP stream affected judgements of overall stream value. The results showed that the presence of an irrelevant high or low value salient item biased people to judge the stream as having a higher or lower overall mean value, respectively. Experiments 4-7 directly tested Tsetsos et al.'s (Proceedings of the National Academy of Sciences of the United States of America, 109(24), 9659-9664, 2012) theory examining whether extreme values in an RSVP stream become over-weighted, thereby capturing attention more than other values in the stream. The results showed that the presence of both a high (Experiments 4, 6 and 7) and a low (Experiment 5) value outlier captures attention leading to less accurate report of subsequent items in the stream. Taken together, the results showed that valuations can be influenced by attentional processes, and can lead to less accurate subjective judgements.}, } @article {pmid28533978, year = {2017}, author = {Holman, L and van Zweden, JS and Oliveira, RC and van Oystaeyen, A and Wenseleers, T}, title = {Conserved queen pheromones in bumblebees: a reply to Amsalem et al.}, journal = {PeerJ}, volume = {5}, number = {}, pages = {e3332}, pmid = {28533978}, issn = {2167-8359}, abstract = {In a recent study, Amsalem, Orlova & Grozinger (2015) performed experiments with Bombus impatiens bumblebees to test the hypothesis that saturated cuticular hydrocarbons are evolutionarily conserved signals used to regulate reproductive division of labor in many Hymenopteran social insects. They concluded that the cuticular hydrocarbon pentacosane (C25), previously identified as a queen pheromone in a congeneric bumblebee, does not affect worker reproduction in B. impatiens. Here we discuss some shortcomings of Amsalem et al.'s study that make its conclusions unreliable. In particular, several confounding effects may have affected the results of both experimental manipulations in the study. Additionally, the study's low sample sizes (mean n per treatment = 13.6, range: 4-23) give it low power, not 96-99% power as claimed, such that its conclusions may be false negatives. Inappropriate statistical tests were also used, and our reanalysis found that C25 substantially reduced and delayed worker egg laying in B. impatiens. We review the evidence that cuticular hydrocarbons act as queen pheromones, and offer some recommendations for future queen pheromone experiments.}, } @article {pmid28530413, year = {2017}, author = {Okun, L and Chang, DF and Kanhai, G and Dunn, J and Easley, H}, title = {Inverting the power dynamic: The process of first sessions of psychotherapy with therapists of color and non-Latino white patients.}, journal = {Journal of counseling psychology}, volume = {64}, number = {4}, pages = {443-452}, doi = {10.1037/cou0000223}, pmid = {28530413}, issn = {0022-0167}, mesh = {Adaptation, Psychological ; Adult ; Female ; *Hispanic or Latino ; Humans ; Male ; *Power, Psychological ; *Professional-Patient Relations ; *Psychotherapy ; *White People ; }, abstract = {The present study is the first to apply Trawalter, Richeson, and Shelton's (2009) stress and coping framework to qualitatively examine interracial interactions in initial sessions of psychotherapy. The sample included 22 dyads: 15 therapists of color administering various treatment modalities to 15 treatment-seeking non-Latino White (NLW) patients and a comparison group of 7 intraracial (NLW-NLW) dyads. In Phase 1, videorecordings of the first session of treatment were analyzed using inductive thematic analysis (TA) to describe patient and therapist behaviors. In Phase 2, a deductive TA approach was used to interpret and cluster those dyadic behaviors according to Trawalter et al.'s (2009) framework. NLW patients paired with therapists of color made more efforts to bridge differences and more often questioned the therapist's professional qualifications compared with those matched with NLW therapists. Therapists of color made more self-disclosures than NLW therapists and maintained a more formal stance, compared with NLW therapists. The deductive TA operationalized 4 of Trawalter and colleagues' (2009) coping responses within a therapeutic framework. Findings highlight the ability of therapists' of color to engage positively with their NLW patients even in the face of challenges to their expertise and credibility. (PsycINFO Database Record}, } @article {pmid28514704, year = {2017}, author = {Hiew, FL and Ramlan, R and Viswanathan, S and Puvanarajah, S}, title = {Guillain-Barré Syndrome, variants & forms fruste: Reclassification with new criteria.}, journal = {Clinical neurology and neurosurgery}, volume = {158}, number = {}, pages = {114-118}, doi = {10.1016/j.clineuro.2017.05.006}, pmid = {28514704}, issn = {1872-6968}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Female ; Guillain-Barre Syndrome/*classification/*diagnosis/*physiopathology ; Humans ; Male ; Middle Aged ; Miller Fisher Syndrome/classification/diagnosis/physiopathology ; Young Adult ; }, abstract = {OBJECTIVES: This study aimed to evaluate the clinical and electrophysiological characteristics of various distinctive classical and localised Guillain-Barré syndrome (GBS) subtypes.

PATIENTS AND METHODS: Clinical characteristics and electrophysiological data of sixty-one consecutive patients admitted between 2012 and 2015 were systematically analysed and reclassified according to the new GBS clinical classification. Neurophysiology was evaluated with Hadden et al.'s vs recently proposed Rajabally et al.'s criteria. Functional severity and clinical outcome of various GBS subtypes were ascertained.

RESULTS: All patients initially identified as GBS or related disorders can be sub-classified into having classical GBS (41, 67%), classic Miller-Fisher Syndrome (MFS) (6, 10%), Pharyngeal-cervical-brachial (PCB) (3, 5%), paraparetic GBS (4, 7%), bifacial weakness with paresthesia (3, 5%), acute ophthalmoparesis (AO) (1, 2%) and overlap syndrome (3, 5%): one (2%) with GBS/Bickerstaff brainstem encephalitis overlap and 2 (3%) with GBS/MFS overlap. Greater proportion of axonal classical GBS (67% vs 55%, p=0.372) seen with Rajabally et al.'s criteria and a predominantly axonal form of paraparetic variant (75%) independent of electrodiagnostic criteria were more representative of Asian GBS cohort. Classical GBS patients had lowest admission and discharge Medical Research Council Sum Score (MRCSS), greater functional disability and longest length of in-patient stay. Twenty (20/21, 95%) patients who needed mechanical ventilation had classical GBS. Patients required repeated dose of intravenous immunoglobulin (5/6, 3%) or plasma exchange (4/4, 100%) more frequently had axonal form of classical GBS.

CONCLUSION: Phenotype recognition based on new GBS clinical classification, supported by electrodiagnostic study permits more precise clinical subtypes determination and outcome prognostication.}, } @article {pmid28478863, year = {2017}, author = {Nikfarid, L and Rassouli, M and Borimnejad, L and Alavimajd, H}, title = {Experience of chronic sorrow in mothers of children with cancer: A phenomenological study.}, journal = {European journal of oncology nursing : the official journal of European Oncology Nursing Society}, volume = {28}, number = {}, pages = {98-106}, doi = {10.1016/j.ejon.2017.02.003}, pmid = {28478863}, issn = {1532-2122}, mesh = {Adaptation, Psychological ; Adolescent ; Adult ; Child ; Child, Preschool ; Chronic Disease/*psychology ; Fear/*psychology ; Female ; *Grief ; Hermeneutics ; Humans ; Infant ; Infant, Newborn ; Iran ; Middle Aged ; Mothers/*psychology ; Neoplasms/*psychology ; }, abstract = {PURPOSE: Chronic sorrow is a multidimensional concept experienced by mothers of children suffering with chronic conditions, e.g. cancer. Little is known about the concept of chronic sorrow and related issues/experiences among mothers of children with cancer living in Iran. This study aimed to explore the concept of chronic sorrow, based on the lived experiences of chronic sorrow experienced in a group of Iranian mothers of children with cancer.

METHODS: In this hermeneutic phenomenological study, 8 mothers of children with cancer participated in semi structured, in-depth interviews about their experiences of chronic sorrow. Interviews continued until data saturation was reached. All interviews were recorded, transcribed, analyzed, and interpreted using the seven steps of the Dickelman et al.'s phenomenological approach.

RESULTS: The three main themes that emerged from mothers' experiences of chronic sorrow related to their child's cancer were "climbing up shaky rocks," "religious fear and hope," and "continuous role changing." Each of these themes consisted of several subthemes. Besides the possibility of growth and coping with the chronic condition of a child which has been seen in other studies on chronic sorrow experiences, religious issues were more profound than what has reported in Western studies. Also the ambiguous prognosis and uncertain process of the cancer in children had made the experience of chronic sorrow more unique.

CONCLUSION: The results of this study show that the experiences of mothers of children with cancer in Iran are not specific to them, but are better comprehended in their traditional socio-cultural context.}, } @article {pmid28472665, year = {2017}, author = {Chen, YZ and Chen, JX and Wu, MJ}, title = {Reply to: Re: Chen et al.'s letter regarding the article "effect of prehospital advanced airway management for pediatric out-of-hospital cardiac arrest. Video laryngoscope use and time to intubation for pediatric out-of-hospital cardiac arrest.}, journal = {Resuscitation}, volume = {116}, number = {}, pages = {e9}, doi = {10.1016/j.resuscitation.2017.04.033}, pmid = {28472665}, issn = {1873-1570}, mesh = {Airway Management ; Child ; Emergency Medical Services ; Humans ; Intubation, Intratracheal ; *Laryngoscopes ; *Out-of-Hospital Cardiac Arrest ; }, } @article {pmid28470131, year = {2017}, author = {Jordan, P and Mpasa, F and Ten Ham-Baloyi, W and Bowers, C}, title = {Implementation strategies for guidelines at ICUs: a systematic review.}, journal = {International journal of health care quality assurance}, volume = {30}, number = {4}, pages = {358-372}, doi = {10.1108/IJHCQA-08-2016-0119}, pmid = {28470131}, issn = {1758-6542}, mesh = {*Critical Illness ; Cross Infection/prevention & control ; Guideline Adherence/*organization & administration ; Humans ; Inservice Training/organization & administration ; Intensive Care Units/*organization & administration/standards ; Leadership ; Medical Errors/prevention & control ; Nutritional Support/standards ; Palliative Care/standards ; *Practice Guidelines as Topic ; Quality of Health Care/standards ; Randomized Controlled Trials as Topic ; }, abstract = {Purpose The purpose of this paper is to critically analyze empirical studies related to the implementation strategies for clinical practice guidelines (CPGs) in intensive care units (ICUs). Design/methodology/approach A systematic review with a narrative synthesis adapted from Popay et al.'s method for a narrative synthesis was conducted. A search using CINAHL, Google Scholar, Academic search complete, Cochrane Register for Randomized Controlled Trials, MEDLINE via PUBMED and grey literature was conducted in 2014 and updated in 2016 (August). After reading the abstracts, titles and full-text articles, 11 (n=11) research studies met the inclusion criteria. Findings After critical appraisal, using the Joanna Briggs Critical Appraisal Tools, eight randomized controlled trials conducted in adult and neonatal ICUs using implementation strategies remained. Popay et al.'s method for narrative synthesis was adapted and used to analyze and synthesize the data and formulate concluding statements. Included studies found that multi-faceted strategies appear to be more effective than single strategies. Strategies mostly used were printed educational materials, information/ sessions, audit, feedback, use of champion leaders, educational outreach visits, and computer or internet usage. Practical training, monitoring visits and grand rounds were less used. Practical implications Findings can be used by clinicians to implement the best combination of multi-faceted implementation strategies in the ICUs in order to enhance the optimal use of CPGs. Originality/value No systematic review was previously done on the implementation strategies that should be used best for optimal CPG implementation in the ICU.}, } @article {pmid28459380, year = {2017}, author = {Ruben, MA and Shipherd, JC and Topor, D and AhnAllen, CG and Sloan, CA and Walton, HM and Matza, AR and Trezza, GR}, title = {Advancing LGBT Health Care Policies and Clinical Care Within a Large Academic Health Care System: A Case Study.}, journal = {Journal of homosexuality}, volume = {64}, number = {10}, pages = {1411-1431}, doi = {10.1080/00918369.2017.1321386}, pmid = {28459380}, issn = {1540-3602}, mesh = {Bisexuality ; Boston ; Cultural Competency ; *Delivery of Health Care ; Female ; *Health Policy ; *Homosexuality ; Humans ; Male ; Mental Health ; Organizational Case Studies ; Sexual Behavior ; *Sexual and Gender Minorities ; Transgender Persons ; Transsexualism ; }, abstract = {Culturally competent health care is especially important among sexual and gender minority patients because poor cultural competence contributes to health disparities. There is a need to understand how to improve health care quality and delivery for lesbian, gay, bisexual, and transgender (LGBT) veterans in particular, because they have unique physical and mental health needs as both LGBT individuals and veterans. The following article is a case study that focuses on the policy and clinical care practices related to LGBT clinical competency, professional training, and ethical provision of care for veteran patients in the VA Boston Healthcare System. We apply Betancourt et al.'s (2003) cultural competence framework to outline the steps that VA Boston Healthcare System took to increase cultural competency at the organizational, structural, and clinical level. By sharing our experiences, we aim to provide a model and steps for other health care systems and programs, including other VA health care systems, large academic health care systems, community health care systems, and mental health care systems, interested in developing LGBT health initiatives.}, } @article {pmid28455568, year = {2017}, author = {Jain, S and Sharma, SK and Choudhary, N and Masiwal, R and Saxena, M and Sharma, A and Mandal, TK and Gupta, A and Gupta, NC and Sharma, C}, title = {Chemical characteristics and source apportionment of PM2.5 using PCA/APCS, UNMIX, and PMF at an urban site of Delhi, India.}, journal = {Environmental science and pollution research international}, volume = {24}, number = {17}, pages = {14637-14656}, pmid = {28455568}, issn = {1614-7499}, mesh = {*Air Pollutants ; Cities ; *Environmental Monitoring ; India ; Pakistan ; *Particulate Matter ; Trace Elements ; Vehicle Emissions ; }, abstract = {The present study investigated the comprehensive chemical composition [organic carbon (OC), elemental carbon (EC), water-soluble inorganic ionic components (WSICs), and major & trace elements] of particulate matter (PM2.5) and scrutinized their emission sources for urban region of Delhi. The 135 PM2.5 samples were collected from January 2013 to December 2014 and analyzed for chemical constituents for source apportionment study. The average concentration of PM2.5 was recorded as 121.9 ± 93.2 μg m[-3] (range 25.1-429.8 μg m[-3]), whereas the total concentration of trace elements (Na, Ca, Mg, Al, S, Cl, K, Cr, Si, Ti, As, Br, Pb, Fe, Zn, and Mn) was accounted for ∼17% of PM2.5. Strong seasonal variation was observed in PM2.5 mass concentration and its chemical composition with maxima during winter and minima during monsoon seasons. The chemical composition of the PM2.5 was reconstructed using IMPROVE equation, which was observed to be in good agreement with the gravimetric mass. Source apportionment of PM2.5 was carried out using the following three different receptor models: principal component analysis with absolute principal component scores (PCA/APCS), which identified five major sources; UNMIX which identified four major sources; and positive matrix factorization (PMF), which explored seven major sources. The applied models were able to identify the major sources contributing to the PM2.5 and re-confirmed that secondary aerosols (SAs), soil/road dust (SD), vehicular emissions (VEs), biomass burning (BB), fossil fuel combustion (FFC), and industrial emission (IE) were dominant contributors to PM2.5 in Delhi. The influences of local and regional sources were also explored using 5-day backward air mass trajectory analysis, cluster analysis, and potential source contribution function (PSCF). Cluster and PSCF results indicated that local as well as long-transported PM2.5 from the north-west India and Pakistan were mostly pertinent.}, } @article {pmid28450052, year = {2017}, author = {Jennings, BJ and Kingdom, FAA}, title = {Chromatic blur perception in the presence of luminance contrast.}, journal = {Vision research}, volume = {135}, number = {}, pages = {34-42}, doi = {10.1016/j.visres.2017.04.006}, pmid = {28450052}, issn = {1878-5646}, support = {//CIHR/Canada ; }, mesh = {Color Perception/*physiology ; Contrast Sensitivity/*physiology ; Humans ; Light ; Photic Stimulation ; Refractive Errors/*physiopathology ; }, abstract = {Hel-Or showed that blurring the chromatic but not the luminance layer of an image of a natural scene failed to elicit any impression of blur. Subsequent studies have suggested that this effect is due either to chromatic blur being masked by spatially contiguous luminance edges in the scene (Journal of Vision 13 (2013) 14), or to a relatively compressed transducer function for chromatic blur (Journal of Vision 15 (2015) 6). To test between the two explanations we conducted experiments using as stimuli both images of natural scenes as well as simple edges. First, we found that in color-and-luminance images of natural scenes more chromatic blur was needed to perceptually match a given level of blur in an isoluminant, i.e. colour-only scene. However, when the luminance layer in the scene was rotated relative to the chromatic layer, thus removing the colour-luminance edge correlations, the matched blur levels were near equal. Both results are consistent with Sharman et al.'s explanation. Second, when observers matched the blurs of luminance-only with isoluminant scenes, the matched blurs were equal, against Kingdom et al.'s prediction. Third, we measured the perceived blur in a square-wave as a function of (i) contrast (ii) number of luminance edges and (iii) the relative spatial phase between the colour and luminance edges. We found that the perceived chromatic blur was dependent on both relative phase and the number of luminance edges, or dependent on the luminance contrast if only a single edge is present. We conclude that this Hel-Or effect is largely due to masking of chromatic blur by spatially contiguous luminance edges.}, } @article {pmid28446891, year = {2017}, author = {Lucidi, F and Zelli, A and Mallia, L and Nicolais, G and Lazuras, L and Hagger, MS}, title = {Moral Attitudes Predict Cheating and Gamesmanship Behaviors Among Competitive Tennis Players.}, journal = {Frontiers in psychology}, volume = {8}, number = {}, pages = {571}, pmid = {28446891}, issn = {1664-1078}, abstract = {Background: The present study tested Lee et al.'s (2008) model of moral attitudes and cheating behavior in sports in an Italian sample of young tennis players and extended it to predict behavior in actual match play. In the first phase of the study we proposed that moral, competence and status values would predict prosocial and antisocial moral attitudes directly, and indirectly through athletes' goal orientations. In the second phase, we hypothesized that moral attitudes would directly predict actual cheating behavior observed during match play. Method: Adolescent competitive tennis players (N = 314, 76.75% males, M age = 14.36 years, SD = 1.50) completed measures of values, goal orientations, and moral attitudes. A sub-sample (n = 90) was observed in 45 competitive tennis matches by trained observers who recorded their cheating and gamesmanship behaviors on a validated checklist. Results: Consistent with hypotheses, athletes' values predicted their moral attitudes through the effects of goal orientations. Anti-social attitudes directly predicted cheating behavior in actual match play providing support for a direct link between moral attitude and actual behavior. Conclusion: The present study findings support key propositions of Lee and colleagues' model, and extended its application to competitive athletes in actual match play.}, } @article {pmid30026910, year = {2017}, author = {Newman, S and Easteal, S}, title = {The dynamic upper limit of human lifespan.}, journal = {F1000Research}, volume = {6}, number = {}, pages = {569}, pmid = {30026910}, issn = {2046-1402}, abstract = {We respond to claims by Dong et al. that human lifespan is limited below 125 years. Using the log-linear increase in mortality rates with age to predict the upper limits of human survival we find, in contrast to Dong et al., that the limit to human lifespan is historically flexible and increasing. This discrepancy can be explained by Dong et al.'s use of data with variable sample sizes, age-biased rounding errors, and log(0) instead of log(1) values in linear regressions. Addressing these issues eliminates the proposed 125-year upper limit to human lifespan.}, } @article {pmid28441331, year = {2017}, author = {Moon, J and Lee, D and Lee, Y and Won, D}, title = {Improving Biometric-Based Authentication Schemes with Smart Card Revocation/Reissue for Wireless Sensor Networks.}, journal = {Sensors (Basel, Switzerland)}, volume = {17}, number = {5}, pages = {}, pmid = {28441331}, issn = {1424-8220}, abstract = {User authentication in wireless sensor networks is more difficult than in traditional networks owing to sensor network characteristics such as unreliable communication, limited resources, and unattended operation. For these reasons, various authentication schemes have been proposed to provide secure and efficient communication. In 2016, Park et al. proposed a secure biometric-based authentication scheme with smart card revocation/reissue for wireless sensor networks. However, we found that their scheme was still insecure against impersonation attack, and had a problem in the smart card revocation/reissue phase. In this paper, we show how an adversary can impersonate a legitimate user or sensor node, illegal smart card revocation/reissue and prove that Park et al.'s scheme fails to provide revocation/reissue. In addition, we propose an enhanced scheme that provides efficiency, as well as anonymity and security. Finally, we provide security and performance analysis between previous schemes and the proposed scheme, and provide formal analysis based on the random oracle model. The results prove that the proposed scheme can solve the weaknesses of impersonation attack and other security flaws in the security analysis section. Furthermore, performance analysis shows that the computational cost is lower than the previous scheme.}, } @article {pmid28432024, year = {2017}, author = {Lemoine, S and Jost, D and Alhanati, L and Tourtier, JP}, title = {Re: Chen et al.'s letter regarding the article "Effect of prehospital advanced airway management for pediatric out-of-hospital cardiac arrest.": Video laryngoscope use and time to intubation for pediatric out-of-hospital cardiac arrest.}, journal = {Resuscitation}, volume = {116}, number = {}, pages = {e7}, doi = {10.1016/j.resuscitation.2017.04.015}, pmid = {28432024}, issn = {1873-1570}, mesh = {Airway Management ; Child ; Emergency Medical Services ; Humans ; Intubation, Intratracheal ; *Laryngoscopes ; *Out-of-Hospital Cardiac Arrest ; }, } @article {pmid28427253, year = {2017}, author = {Su, M and Guo, J and Huang, J}, title = {Meta-analysis of the correlation between the rs17401966 polymorphism in kinesin family member 1B and susceptibility to hepatitis B virus related hepatocellular carcinoma.}, journal = {Clinical and molecular hepatology}, volume = {23}, number = {2}, pages = {138-146}, pmid = {28427253}, issn = {2287-285X}, mesh = {Alleles ; Carcinoma, Hepatocellular/complications/*diagnosis/genetics ; Case-Control Studies ; Databases, Factual ; Gene Frequency ; *Genetic Predisposition to Disease ; Hepatitis B virus/isolation & purification ; Hepatitis B, Chronic/complications/*diagnosis/virology ; Humans ; Kinesins/*genetics ; Liver Neoplasms/complications/*diagnosis/genetics ; Odds Ratio ; Polymorphism, Single Nucleotide ; Risk Factors ; }, abstract = {BACKGROUND/AIMS: The association between the kinesin family member 1B (KIF1B) gene polymorphism and the risk of hepatitis B virus-related hepatocellular carcinoma (HCC) has been investigated in many peer-reviewed studies. However, scholars have failed to replicate these results in validation tests. The purpose of the present study was to explore whether the KIF1B rs17401966 polymorphism was associated with susceptibility to HCC.

METHODS: The results of case-controlled studies on the correlation between the KIF1B rs17401966 polymorphism and HCC susceptibility were collected using Google Scholar and the EMBASE, PubMed and CNKI databases. Based on inclusion and exclusion criteria, 5 papers with a total of 12 cohorts were included in this study.

RESULTS: The 12 cohorts were integrated, and the results showed that the rs17401966 polymorphism reduced the risk for HCC under the allele, heterozygous, homozygous, and dominant models but not under the additive or recessive models. Moreover, the merged results showed strong heterogeneity, and the cumulative meta-analysis results were unreliable. A genetic differentiation analysis of the 12 cohorts found different degrees of genetic differentiation between the 5 cohorts in Zhang et al.'s study and the cohorts in the other studies. We further divided the 12 study cohorts into 2 subgroups based on fixation index value; however, the results of that analysis were inconsistent.

CONCLUSIONS: The results of this meta-analysis were not able to verify the association between the KIF1B rs1740199 polymorphism and HCC risk. Therefore, a well-designed, large-scale, multicenter validation study is needed to confirm the relationship.}, } @article {pmid28419697, year = {2018}, author = {Franklin, ZC and Fowler, NE}, title = {Defensive High-Anxious Individuals Demonstrate Difference Responses to Pain Management to Those with Lower Levels of Defensiveness and Anxiety.}, journal = {Pain practice : the official journal of World Institute of Pain}, volume = {18}, number = {2}, pages = {214-223}, doi = {10.1111/papr.12595}, pmid = {28419697}, issn = {1533-2500}, mesh = {Adult ; Anxiety/psychology ; Chronic Pain/*psychology/*therapy ; Female ; Humans ; Male ; Middle Aged ; Pain Management/*psychology ; *Personality ; Surveys and Questionnaires ; }, abstract = {OBJECTIVES: Few studies have considered the effect of Weinberger et al.'s personality types on the management of pain. The aims of this study were to (1) identify whether the relationships between pain intensity, cognitive factors, and disability at 3 and 6 months postbaseline differ as a result of personality type; and (2) identify whether personality type affects the likelihood of achieving a minimal clinically important change in pain intensity or disability at 3 and 6 months.

METHOD: Patients completed a set of validated questionnaires assessing personality type, cognitive factors, pain intensity, and disability at 3 and 6 months postbaseline.

RESULTS: A greater proportion of defensive high-anxious individuals reported improvement for both pain (3 months = 25%; 6 months = 38%) and disability (3 months = 35%; 6 months = 50%) and showed stronger links between improvements in pain and disability and baseline psychological factors than nonextreme individuals.

CONCLUSIONS: The high proportion of defensive high-anxious individuals highlights the need for psychologically based interventions to be delivered earlier in the care process. Stratifying the population, based on personality type, may allow for more targeted interventions, which could be more cost effective and reduce the number of patients remaining in the care system.}, } @article {pmid28405908, year = {2018}, author = {Perea, M and Winskel, H and Gomez, P}, title = {How orthographic-specific characteristics shape letter position coding: The case of Thai script.}, journal = {Psychonomic bulletin & review}, volume = {25}, number = {1}, pages = {416-422}, pmid = {28405908}, issn = {1531-5320}, support = {PSI2014-53444-P//Spanish Ministry of Economy and Competitiveness/International ; }, mesh = {Adult ; Attention ; Humans ; *Language ; *Orientation ; *Pattern Recognition, Visual ; Psycholinguistics ; *Reading ; *Semantics ; *Spatial Learning ; Thailand ; Verbal Learning ; *Writing ; }, abstract = {A central question for any model of visual word identification is the representation of the position at which letters are encoded (e.g., calm vs. clam). In this article, we examine whether the orthographic-specific characteristics of a writing system-namely, Thai-shape the process of letter position coding. Thai is an alphabetic script that lacks interword spaces and has an orthographic order that does not necessarily correspond to the phonological order for initial vowels. This implies that the initial letter position coding in Thai needs to be flexible enough that readers can successfully encode the letter positions of words. To compare letter position coding in Thai to that in English, we conducted an experiment that paralleled Experiment 3 in Gomez, Ratcliff, and Perea (Psychological Review, 115, 577-600, 2008), including 23 conditions (single-letter replacements, letter transpositions, letter migrations, and a corresponding control). We obtained fits from Gomez et al.'s overlap model, which is a model that has been shown to account for letter position coding in the Roman alphabet across this variety of letter manipulations. The overlap model was found to successfully fit the Thai data. Our results revealed that the position encoding was better for the first letter than for the rest of the positions in both languages; however, in English the position uncertainty grows as a function of letter order quite abruptly, whereas in Thai it grows gradually. Thus, the orthographic-specific characteristics of the Thai writing system do play a role in shaping the process of letter position coding.}, } @article {pmid28403749, year = {2017}, author = {Slotnick, SD}, title = {Cluster success: fMRI inferences for spatial extent have acceptable false-positive rates.}, journal = {Cognitive neuroscience}, volume = {8}, number = {3}, pages = {150-155}, doi = {10.1080/17588928.2017.1319350}, pmid = {28403749}, issn = {1758-8936}, mesh = {Humans ; *Magnetic Resonance Imaging ; }, abstract = {In an editorial (this issue), I argued that Eklund, Nichols, and Knutsson's 'null data' reflected resting-state/default network activity that inflated their false-positive rates. Commentaries on that paper were received by Nichols, Eklund, and Knutsson (this issue), Hopfinger (this issue), and Cunningham and Koscik (this issue). In this author response, I consider these commentaries. Many issues stemming from Nichols et al. are identified including: (1) Nichols et al. did not provide convincing arguments that resting-state fMRI data reflect null data. (2) Eklund et al. presented one-sample t-test results in the main body of their paper showing that their permutation method was acceptable, while their supplementary results showed that this method produced false-positive rates that were similar to other methods. (3) Eklund et al. used the same event protocol for all the participants, which artifactually inflated the one-sample t-test false-positive rates. (4) At p < .001, using two-sample t-tests (which corrected for the flawed analysis), all the methods employed to correct for multiple comparisons had acceptable false-positive rates. (5) Eklund et al. contrasted resting-state periods, which produced many significant clusters of activity, while null data should arguably be associated with few, if any, significant activations. Eklund et al.'s entire set of results show that commonly employed methods to correct for multiple comparisons have acceptable false-positive rates. Following Hopfinger along with Cunningham and Koscik, it is also highlighted that rather than focusing on only type I error, type I error and type II error should be balanced in fMRI analysis.}, } @article {pmid28388855, year = {2019}, author = {Rice, KG and Gnilka, PB and Davis, DE and Ashby, JS}, title = {Addressing Concerns About How Perfectionistic Discrepancy Should Be Measured With the Revised Almost Perfect Scale.}, journal = {Assessment}, volume = {26}, number = {3}, pages = {432-444}, doi = {10.1177/1073191117702241}, pmid = {28388855}, issn = {1552-3489}, mesh = {Adult ; Factor Analysis, Statistical ; Female ; Humans ; Male ; Models, Psychological ; *Perfectionism ; Personality Tests/*standards ; Psychometrics ; Reproducibility of Results ; Students ; Universities ; Young Adult ; }, abstract = {We examine the conceptual and empirical merits of concerns Flett et al. recently raised about the Almost Perfect Scale-Revised (APS-R), specifically that items on the APS-R Discrepancy should be separated into a "Pure" Discrepancy factor and a Dissatisfaction factor. Limitations in the logic and findings of that critique are summarized. We replicate and extend Flett et al.'s study with results from two samples: (a) college freshmen STEM students (N = 279) and (b) doctoral students in a national sample (N = 529). Confirmatory factor analyses indicated that the alternative measurement models could be fit to the data, but were not practical improvements over the original APS-R factor model: Alternative discrepancy factors failed to demonstrate discriminant validity, nor did they have meaningfully different patterns of associations with numerous criterion variables (i.e., stress, emotion regulation, rumination, adult attachment, and life satisfaction). Thus, a data-based answer to the question of how perfectionistic discrepancy should be assessed is to stay the course with confidence using the original APS-R.}, } @article {pmid28376357, year = {2017}, author = {Pryma, J}, title = {"Even my sister says I'm acting like a crazy to get a check": Race, gender, and moral boundary-work in women's claims of disabling chronic pain.}, journal = {Social science & medicine (1982)}, volume = {181}, number = {}, pages = {66-73}, doi = {10.1016/j.socscimed.2017.03.048}, pmid = {28376357}, issn = {1873-5347}, mesh = {Adult ; Chronic Pain/ethnology/etiology/psychology ; *Disability Evaluation ; Female ; Fibromyalgia/*complications/epidemiology/ethnology ; Humans ; Morals ; Qualitative Research ; Racial Groups/ethnology/*statistics & numerical data ; *Sex Factors ; *Social Stigma ; Social Welfare/ethnology/psychology ; United States/epidemiology ; }, abstract = {Recent research examines how women claim chronic pain in response to gendered moral discourses. However, extant research does not explore how race shapes the moral boundary-work performed by women suffering from disabling chronic pain. Through the qualitative analysis of twenty-four semi-structured interviews with women fibromyalgia sufferers conducted between October 2014 and August 2016 in the U.S.A., I demonstrate how women with fibromyalgia claim chronic pain by doing moral boundary-work, referencing gendered and racialized moral discourses that structure how claims of chronic pain as disability are and are not read as legitimate by doctors, disability bureaucrats and personal networks. Extending Hansen et al.'s work on stigma and the "pathologization of poverty," I suggest that, per my sample, the different moral discourses deployed in white and Black women's claims of chronic pain can be explained by the racialized and gendered boundaries of citizenship that structure U.S. welfare and disability politics. Finally, I argue for intersectionality's relevance to research on moral boundary-work and the medicalization of poverty.}, } @article {pmid28376273, year = {2017}, author = {Aguilar-Huaman, DM and Caballero-García, S and Pereyra-Elías, R and Segura, ER and Abanto, J and , }, title = {Overall assessment of responsiveness to change is just the very first step: a technical commentary on Abanto et al.'s study.}, journal = {International journal of paediatric dentistry}, volume = {27}, number = {3}, pages = {228-229}, doi = {10.1111/ipd.12297}, pmid = {28376273}, issn = {1365-263X}, mesh = {Child, Preschool ; *Dental Caries ; Humans ; }, } @article {pmid28374287, year = {2017}, author = {Gainotti, G}, title = {The Differential Contributions of Conceptual Representation Format and Language Structure to Levels of Semantic Abstraction Capacity.}, journal = {Neuropsychology review}, volume = {27}, number = {2}, pages = {134-145}, pmid = {28374287}, issn = {1573-6660}, mesh = {Concept Formation/*physiology ; Frontotemporal Dementia/*pathology/*physiopathology ; Humans ; *Language ; Temporal Lobe/*pathology ; }, abstract = {This paper reviews some controversies concerning the original and revised versions of the 'hub-and-spoke' model of conceptual representations and their implication for abstraction capacity levels. The 'hub-and-spoke' model, which is based on data gathered in patients with semantic dementia (SD), is the most authoritative model of conceptual knowledge. Patterson et al.'s (Nature Reviews Neuroscience, 8(12), 976-987, 2007) classical version of this model maintained that conceptual representations are stored in a unitary 'amodal' format in the right and left anterior temporal lobes (ATLs), because in SD the semantic disorder cuts across modalities and categories. Several authors questioned the unitary nature of these representations. They showed that the semantic impairment is 'multi-modal'only in the advanced stages of SD, when atrophy affects the ATLs bilaterally, but that impariments can be modality-specific in lateralised (early) stages of the disease. In these cases, SD mainly affects lexical-semantic knowledge when atrophy predominates on the left side and pictorial representations when atrophy prevails on the right side. Some aspects of the model (i.e. the importance of spokes, the multimodal format of representations and the graded convergence of modalities within the ATLs), which had already been outlined by Rogers et al. (Psychological Review, 111(1), 205-235, 2004) in a computational model of SD, were strengthened by these results. The relevance of these theoretical problems and of empirical data concerning the neural substrate of concrete and abstract words is discussed critically. The conclusion of the review is that the highest levels of abstraction are due more to the structuring influence of language than to the format of representations.}, } @article {pmid28372645, year = {2017}, author = {Logvinov, II and Dexter, F and Hindman, BJ and Brull, SJ}, title = {Anesthesiologists' perceptions of minimum acceptable work habits of nurse anesthetists.}, journal = {Journal of clinical anesthesia}, volume = {38}, number = {}, pages = {107-110}, doi = {10.1016/j.jclinane.2017.01.031}, pmid = {28372645}, issn = {1873-4529}, mesh = {Anesthesiologists/*psychology ; Anesthesiology/standards ; Employee Performance Appraisal/methods ; Female ; *Habits ; Humans ; Male ; Nurse Anesthetists/*psychology ; *Perception ; *Professional Practice ; Surveys and Questionnaires ; }, abstract = {STUDY OBJECTIVE: Work habits are non-technical skills that are an important part of job performance. Although non-technical skills are usually evaluated on a relative basis (i.e., "grading on a curve"), validity of evaluation on an absolute basis (i.e., "minimum passing score") needs to be determined.

DESIGN: Survey and observational study.

PATIENTS: None.

INTERVENTIONS: None.

MEASUREMENTS: The theme of "work habits" was assessed using a modification of Dannefer et al.'s 6-item scale, with scores ranging from 1 (lowest performance) to 5 (highest performance). E-mail invitations were sent to all consultant and fellow anesthesiologists at Mayo Clinic in Florida, Arizona, and Minnesota. Because work habits expectations can be generational, the survey was designed for adjustment based on all invited (responding or non-responding) anesthesiologists' year of graduation from residency.

MAIN RESULTS: The overall mean±standard deviation of the score for anesthesiologists' minimum expectations of nurse anesthetists' work habits was 3.64±0.66 (N=48). Minimum acceptable scores were correlated with the year of graduation from anesthesia residency (linear regression P=0.004). Adjusting for survey non-response using all N=207 anesthesiologists, the mean of the minimum acceptable work habits adjusted for year of graduation was 3.69 (standard error 0.02). The minimum expectations for nurse anesthetists' work habits were compared with observational data obtained from the University of Iowa. Among 8940 individual nurse anesthetist work habits scores, only 2.6% were <3.69. All N=65 of the Iowa nurse anesthetists' mean work habits scores were significantly greater than the Mayo estimate (3.69) for the minimum expectations; all P<0.00024.

CONCLUSIONS: Our results suggest that routinely evaluated work habits of nurse anesthetists within departments should not be compared with an appropriate minimum score (i.e., of 3.69). Instead, work habits scores should be analyzed based on relative reporting among anesthetists.}, } @article {pmid28364967, year = {2018}, author = {Courtois, R and Petot, JM and Lignier, B and Lecocq, G and Plaisant, O}, title = {[Does the French Big Five Inventory evaluate facets other than the Big Five factors?].}, journal = {L'Encephale}, volume = {44}, number = {3}, pages = {208-214}, doi = {10.1016/j.encep.2017.02.004}, pmid = {28364967}, issn = {0013-7006}, mesh = {Adolescent ; Adult ; Depression/psychology ; Emotions ; Factor Analysis, Statistical ; Female ; France ; Humans ; Male ; Middle Aged ; Neurotic Disorders/diagnosis/psychology ; Personality Inventory/*standards ; Psychometrics ; Reproducibility of Results ; Self Report ; Students/psychology ; Universities ; Young Adult ; }, abstract = {INTRODUCTION: The Big Five Inventory (BFI) developed by John et al. (1991) is one of the most widely accepted tools for assessing dimensions of personality. It comprises 44 items that assess five broad dimensions of personality (the Big Five Factors): Extraversion, Agreeableness, Conscientiousness, Neuroticism and Openness to experience. Based on correlations with the facets described in the NEO Personality Inventory Revised (NEO PI-R), another Big Five assessment tool with 240 items and 6 facets per dimension, Soto and John (2009) showed that the dimensions in the BFI could be divided into two facets each (ten facets altogether). These results are in line with those of DeYoung et al. (2007), who ran factorial analyses with all the NEO PI-R facets and the International Personality Item Pool (IPIP) and identified ten intermediate factors (between facets and dimensions) which they called "aspects" (two per dimension). The goal of the present study is to investigate the ten facets described by Soto and John in a French sample, using the French version of the BFI (BFI-Fr), which has good psychometric properties, and to check whether the pattern of correlations of these facets with the NEO PI-R match those of the American version.

METHOD: We created three groups. The first comprised 360 students from the Institut libre d'éducation physique supérieure (ILEPS) and Tours University (psychology undergraduates). Participants (mean age 21.1 years±2.30; 58% women) completed the BFI-Fr and the NEO PI-R. The second comprised 142 psychology students from Tours University (mean age 20.6 years±1.78; 81% women); they completed the BFI-Fr twice, two weeks apart (test and retest). The third comprised 252 psychology students from Paris-Nanterre University (mean age 23 years±4.2; 89% women) who described a total of 405 people they knew well (mean age 35.2±10.8; 49% women) using the peer-report format of the BFI-Fr.

RESULTS: In the self-report format, eight of Soto and John's ten aspects had acceptable internal consistency (based on Guildford's (1954) internal consistency criteria, due to the small number of items), with Cronbach's α between 0.60 and 0.86 and test-retest correlations between 0.71 and 0.89, showing satisfactory temporal stability. We found a single facet for Extraversion (Assertiveness), two for Agreeableness (Altruism and Compliance), two for Conscientiousness (Self-Discipline and Order), one for Neuroticism (Anxiety), and two for Openness to Experience (Openness to aesthetics and Openness to ideas). Based on their convergence with the corresponding facets in the NEO PI-R, these eight facets showed satisfactory external validity. With regard to the peer-report format, the Activity facet of Extraversion, which did not have sufficient internal consistency in the self-report format, had acceptable properties (i.e. 9 out of 10 facets). Only the Depression facet of Neuroticism still had insufficient internal consistency. In this study, we proposed an improvement of two facets (Activity and Compliance) and added one facet specific to the French version (Emotional Instability) in place of the Depression facet.

DISCUSSION: We showed that the BFI-Fr can be used to assess nine of the ten facets described by Soto and John. We also identified an Emotional Instability facet, replacing the Depression facet of Neuroticism. DeYoung et al. (2007) considered that anxiety and depression are indissociable and can be represented by a Neuroticism aspect they labeled Withdrawal. They suggested a second aspect of this dimension they called Volatility (with the N2 Angry Hostility facet of the NEO PI-R as main marker and the N5 Impulsiveness and N3 Depression as secondary markers). The Emotional Instability facet we found corresponds closely to the N2 Angry Hostility facet of the NEO PI-R and appears to be a satisfactory marker of DeYoung et al.'s (2007) Volatility aspect. Although this study has limitations, particularly related to the samples (students), the BFI-Fr facets (derived from those defined by Soto and John in the BFI or proposed as improvements on the original facets) match the corresponding NEO PI-R facets and can also be seen as main markers of the aspects defined by DeYoung et al.}, } @article {pmid28357195, year = {2017}, author = {Odongo, DO and Wakhungu, WJ and Stanley, O}, title = {Causes of variability in prevalence rates of communicable diseases among secondary school Students in Kisumu County, Kenya.}, journal = {Zeitschrift fur Gesundheitswissenschaften = Journal of public health}, volume = {25}, number = {2}, pages = {161-166}, pmid = {28357195}, issn = {2198-1833}, abstract = {PURPOSE: To determine causes of variability in communicable disease prevalence rates among students in secondary schools to inform policy formulation in the public health sector.

METHODS: A representative cluster sample size for students was estimated using Fisher et al.'s formula while schools, sub-counties and education zones were clustered and sample size was calculated based on coefficient of variation by school type. Data were collected by questionnaire, medical examination using standard procedures, and focus group discussion, and descriptive analysis was performed on the completed questions. Comparisons between risk factors were made by chi-square and ANOVA analysis using SPSS for Windows (version 15.2; Chicago, IL) software. A p value of < 0.05 was considered statistically significant.

RESULTS: There was significant variation between communicable disease prevalence rates and age (X[2]4, 0.05 = 2.458), school size (X[2]12, 0.05 = 18.636), gender (X[2]4, 0.05 = 5.723) and class of students (X[2]12, 0.05 = 15.202), and bed and desk spacing (p < 0.05 at 95% CI). However, there was no significant association in prevalence rates between both locality and type of school. There was strong evidence that student age has an effect on prevalence rates. The prevalence rate of malaria was higher in male (14.02%) than female students (6.68%) compared to prevalence of diarrhea, which was higher in female (7.96%) than male students.

CONCLUSION: This study has revealed that the prevalences of diarrhea, tuberculosis, pneumonia and other respiratory tract infections are lower among female secondary school students than males and that the prevalence of malaria is higher in males than females. Age of secondary school students is a significant vulnerability factor for malaria, diarrhea, tuberculosis and pneumonia, which were the important communicable diseases most prevalent among secondary school students in Kisumu County, Kenya.}, } @article {pmid28356486, year = {2017}, author = {Adams, JC}, title = {Caveat emptor: for researchers, a rose will not smell sweet unless we know its composition.}, journal = {Bioscience reports}, volume = {37}, number = {3}, pages = {}, pmid = {28356486}, issn = {1573-4935}, mesh = {Aggrecans/chemistry ; Biglycan/chemistry ; Decorin/chemistry ; Fibromodulin/chemistry ; Leucine/*chemistry ; Proteoglycans/*blood ; Tissue Engineering/methods ; Transforming Growth Factor beta/antagonists & inhibitors ; }, abstract = {In a recent publication in Bioscience Reports "Contaminants in commercial preparations of 'purified' small leucine-rich proteoglycans may distort mechanistic studies", Brown et al. identified by mass spectrometry and immunoblotting that certain commercial preparations of the small leucine-rich proteoglycans (SLRPs) decorin and biglycan, in fact, contained a mix of several proteoglycans that also included fibromodulin and aggrecan. The preparations were thus not suitable to study specific activities of decorin or biglycan. Decorin and biglycan are widely studied SLRPs that are considered to have highly multi-functional effects on cells. Decorin is of interest as a transforming growth factor-β antagonist and is also finding use in tissue engineering materials. This Commentary discusses Brown et al.'s findings and general issues raised for researchers who work with commercially sourced purified proteoglycans.}, } @article {pmid28346754, year = {2017}, author = {Singh, I}, title = {Commentary: What makes a life go well? Moral functioning and quality of life measurement in neurodevelopmental disorders - reflections on Jonsson et al. (2017).}, journal = {Journal of child psychology and psychiatry, and allied disciplines}, volume = {58}, number = {4}, pages = {470-473}, doi = {10.1111/jcpp.12716}, pmid = {28346754}, issn = {1469-7610}, mesh = {Humans ; Morals ; Neurodevelopmental Disorders ; Parents ; *Proxy ; *Quality of Life ; Surveys and Questionnaires ; }, abstract = {Jonsson et al.'s excellent review of the literature on quality of life (QoL) and childhood mental and behavioural disorders (Jonsson et al.,) highlights the need for studies that utilise child self-reported QoL, in contrast to parent or proxy QoL measures, and further challenges the field to develop QoL measures that 'put the child's own views and priorities first'.}, } @article {pmid28337158, year = {2017}, author = {Orosz, G and Péter-Szarka, S and Bőthe, B and Tóth-Király, I and Berger, R}, title = {How Not to Do a Mindset Intervention: Learning from a Mindset Intervention among Students with Good Grades.}, journal = {Frontiers in psychology}, volume = {8}, number = {}, pages = {311}, pmid = {28337158}, issn = {1664-1078}, abstract = {The present study examined the effectiveness of a Growth Mindset intervention based on Dweck et al.'s (1995) theory in the Hungarian educational context. A cluster randomized controlled trial classroom experiment was carried out within the framework of a train-the-trainer intervention among 55 Hungarian 10th grade students with high Grade Point Average (GPA). The results suggest that students' IQ and personality mindset beliefs were more incremental in the intervention group than in the control group 3 weeks after the intervention. Furthermore, compared to both the baseline measure and the control group, students' amotivation decreased. However, no intrinsic and extrinsic motivation change was found. Students with low grit scores reported lower amotivation following the intervention. However, in the second follow-up measurement-the end of the semester-all positive changes disappeared; and students' GPA did not change compared to the previous semester. These results show that mindset beliefs are temporarily malleable and in given circumstances, they can change back to their pre-intervention state. The potential explanation is discussed in the light of previous mindset intervention studies and recent findings on wise social psychological interventions.}, } @article {pmid28327989, year = {2017}, author = {Little, MA and Varoquaux, G and Saeb, S and Lonini, L and Jayaraman, A and Mohr, DC and Kording, KP}, title = {Using and understanding cross-validation strategies. Perspectives on Saeb et al.}, journal = {GigaScience}, volume = {6}, number = {5}, pages = {1-6}, pmid = {28327989}, issn = {2047-217X}, mesh = {*Machine Learning ; *Research Design ; }, abstract = {This three-part review takes a detailed look at the complexities of cross-validation, fostered by the peer review of Saeb et al.'s paper entitled "The need to approximate the use-case in clinical machine learning." It contains perspectives by reviewers and by the original authors that touch upon cross-validation: the suitability of different strategies and their interpretation.}, } @article {pmid28301177, year = {2017}, author = {Bostyn, DH and Roets, A}, title = {Trust, trolleys and social dilemmas: A replication study.}, journal = {Journal of experimental psychology. General}, volume = {146}, number = {5}, pages = {e1-e7}, doi = {10.1037/xge0000295}, pmid = {28301177}, issn = {1939-2222}, mesh = {*Cooperative Behavior ; Game Theory ; Humans ; Interpersonal Relations ; *Judgment ; *Morals ; *Trust ; }, abstract = {UNLABELLED: The present manuscript addresses how perceived trustworthiness of cooperative partners in a social dilemma context is influenced by the moral judgments those partners make on Trolley-type moral dilemmas; an issue recently investigated by Everett, Pizarro, and Crockett (2016). The present research comprises 2 studies that were conducted independently, simultaneously with, and incognizant of the Everett studies. Whereas the present studies aimed at investigating the same research hypothesis, a different and more elaborate methodology was used, as such providing a conceptual replication opportunity and extension to the Everett et al.

STUDIES: Overall, the present studies clearly confirmed the main finding of Everett et al., that deontologists are more trusted than consequentialists in social dilemma games. Study 1 replicates Everett et al.'s effect in the context of trust games. Study 2 generalizes the effect to public goods games, thus demonstrating that it is not specific to the type of social dilemma game used in Everett et al. Finally, both studies build on these results by demonstrating that the increased trust in deontologists may sometimes, but not always, be warranted: deontologists displayed increased cooperation rates but only in the public goods game and not in trust games. (PsycINFO Database Record}, } @article {pmid28287767, year = {2017}, author = {Wanzel, SK and Schultze, T and Schulz-Hardt, S}, title = {Disentangling the effects of advisor consensus and advice proximity.}, journal = {Journal of experimental psychology. Learning, memory, and cognition}, volume = {43}, number = {10}, pages = {1669-1675}, doi = {10.1037/xlm0000396}, pmid = {28287767}, issn = {1939-1285}, support = {//Deutsche Forschungsgemeinschaft/ ; }, mesh = {Adult ; Analysis of Variance ; *Consensus ; *Decision Making ; Female ; Humans ; Information Dissemination ; *Judgment ; Male ; Psychological Tests ; Social Behavior ; Young Adult ; }, abstract = {When advice comes from interdependent sources (e.g., from advisors who use the same database), less information should be gained as compared to independent advice. On the other hand, since individuals strive for consistency, they should be more confident in consistent compared to conflicting advice, and interdependent advice should be more consistent than independent advice. In a study investigating the differential effects of interdependent versus independent advice on a judge's accuracy and confidence (Yaniv, Choshen-Hillel, & Milyavsky, 2009), advice interdependence was confounded with another variable, namely closeness of the advice to the judge's estimate. Interdependent advice was not only more consistent than independent advice but also closer to the judge's first estimate. The present study aimed at disentangling the effects of consensus and closeness of the advice by adding a third experimental condition in which interdependent (and, hence, consistent) advice was far from the judge's own estimate. We found that, as suggested by Yaniv et al., accuracy gains were indeed a consequence of advisor interdependence. However, in contrast to Yaniv et al.'s conclusions, confidence in the correctness of one's estimates was mostly a function of the advice's proximity to the participants' initial estimations, thereby indicating a social validation effect. (PsycINFO Database Record}, } @article {pmid28282866, year = {2017}, author = {Lercher, P and Tchounwou, PB}, title = {Comments by the Academic Editors to Responses and Replies Concerning Mroczek et al.'s "Evaluation of Quality of Life of Those Living near a Wind Farm": Int. J. Environ. Res. Public Health 2015, 12, 6066-6083.}, journal = {International journal of environmental research and public health}, volume = {14}, number = {3}, pages = {}, pmid = {28282866}, issn = {1660-4601}, mesh = {Farms ; Humans ; *Quality of Life ; *Wind ; }, } @article {pmid28281895, year = {2017}, author = {Lam, D and Koch, GG and Preisser, JS and Saville, BR and Hussey, MA}, title = {Randomization-based adjustment of multiple treatment hazard ratios for covariates with missing data.}, journal = {Journal of biopharmaceutical statistics}, volume = {27}, number = {3}, pages = {373-386}, doi = {10.1080/10543406.2017.1289954}, pmid = {28281895}, issn = {1520-5711}, mesh = {Computer Simulation ; Confidence Intervals ; Data Accuracy ; *Data Interpretation, Statistical ; Humans ; *Proportional Hazards Models ; *Randomized Controlled Trials as Topic ; *Research Design ; }, abstract = {Clinical trials are designed to compare treatment effects when applied to samples from the same population. Randomization is used so that the samples are not biased with respect to baseline covariates that may influence the efficacy of the treatment. We develop randomization-based covariance adjustment methodology to estimate the log hazard ratios and their confidence intervals of multiple treatments in a randomized clinical trial with time-to-event outcomes and missingness among the baseline covariates. The randomization-based covariance adjustment method is a computationally straight-forward method for handling missing baseline covariate values.}, } @article {pmid28281160, year = {2017}, author = {Redden, RS and d'Entremont, G and Klein, RM}, title = {Further evidence in favor of prior entry from endogenous attention to a location in space.}, journal = {Attention, perception & psychophysics}, volume = {79}, number = {4}, pages = {1027-1038}, doi = {10.3758/s13414-017-1290-0}, pmid = {28281160}, issn = {1943-393X}, mesh = {Adolescent ; Adult ; Attention/*physiology ; Consciousness/physiology ; Cues ; Female ; Humans ; *Judgment ; Male ; Orientation/*physiology ; Photic Stimulation/*methods ; Random Allocation ; Space Perception/*physiology ; Visual Perception/physiology ; Young Adult ; }, abstract = {Titchener's (1908) law of prior entry states that "the object of attention comes to consciousness more quickly than the objects which we are not attending to," or otherwise, that attended stimuli are perceived earlier than unattended stimuli. Shore, Spence, and Klein (Psychological Science, 12, 205-212. doi: 10.1111/1467-9280.00337 , 2001) showed that endogenous visuospatial orienting does in fact elicit prior-entry effects, albeit to a smaller degree than does exogenous visuospatial orienting. In disagreement with this finding, Schneider and Bavelier (Cognitive Psychology, 47, 333-366. doi: 10.1016/S0010-0285(03)00035-5 , 2003) found no effect of their instruction to attend. They concluded that nonattentional effects could masquerade as prior entry, which could account for findings such as those in Shore et al.'s endogenous condition. We investigated this empirical and theoretical discord by replicating the temporal-order judgment task used by Shore, Spence, and Klein, while manipulating and measuring endogenous orienting by way of an orthogonal color probe task. We showed evidence of prior entry as a consequence of endogenous orienting, supporting the conclusions of Shore, Spence, and Klein.}, } @article {pmid28277720, year = {2017}, author = {Neiworth, JJ and London, JM and Flynn, MJ and Rupert, DD and Alldritt, O and Hyde, C}, title = {Artificial grammar learning in tamarins (Saguinus oedipus) in varying stimulus contexts.}, journal = {Journal of comparative psychology (Washington, D.C. : 1983)}, volume = {131}, number = {2}, pages = {128-138}, pmid = {28277720}, issn = {1939-2087}, support = {R15 HD072571/HD/NICHD NIH HHS/United States ; }, mesh = {Animals ; Auditory Perception ; Humans ; *Language ; *Learning ; Saguinus ; }, abstract = {The human ability to detect regularities in sound sequences is a fundamental substrate of our language faculty. However, is this an ability exclusive to human language processing, or have we usurped a more general learning mechanism for this purpose, one shared with other species? The current study is an attempt to replicate and extend Hauser, Weiss, and Marcus's (2002) retracted study (2010) of artificial grammar learning in tamarins to determine if tamarins can detect an underlying grammatical structure in a pattern of sounds. Human language consonant-vowel (CV) combinations from Hauser et al.'s original study, newly created tone sequences, and newly created monkey vocalizations made into sequences were used to familiarize tamarins to an AAB or ABB pattern. Tests of novel sounds in each condition were presented that either were consistent with the familiarized pattern or were different from it. Longer looking times toward the sound source (an audio speaker with a specific location in the auditory field) indicated recognition of novelty. Tamarins looked toward the speaker significantly longer with inconsistent human language CV sequences and with inconsistent tone sequences but not when an inconsistent monkey vocalization was presented. Moreover, tamarins showed differential rates of habituation to the different types of sound patterns, with more robust habituation to CV sequences and tone sequences than to monkey call sequences. The implications of these findings for the generality of learning mechanisms for linguistic and nonlinguistic input across species and the importance of testing across various stimuli are discussed. (PsycINFO Database Record}, } @article {pmid28277203, year = {2017}, author = {Price, A and Schwartz, R and Cohen, J and Manson, H and Scott, F}, title = {Assessing Continuous Quality Improvement in Public Health: Adapting Lessons from Healthcare.}, journal = {Healthcare policy = Politiques de sante}, volume = {12}, number = {3}, pages = {34-49}, pmid = {28277203}, issn = {1715-6580}, mesh = {Adult ; Delivery of Health Care/*organization & administration ; Female ; Humans ; Male ; Middle Aged ; Ontario ; Organizational Culture ; Quality Improvement/*organization & administration ; Total Quality Management/*organization & administration ; United States ; United States Public Health Service/*organization & administration ; }, abstract = {CONTEXT: Evidence of the effect of continuous quality improvement (CQI) in public health and valid tools to judge that such effects are not fully formed.

OBJECTIVE: The objective was to adapt and apply Shortell et al.'s (1998) four dimensions of CQI in an examination of a public health accountability and performance management initiative in Ontario, Canada.

METHODS: In total, 24 semi-structured, in-depth interviews were conducted with informants from public health units and the Ministry of Health and Long-Term Care. A web survey of public health managers in the province was also carried out.

RESULTS: A mix of facilitators and barriers was identified. Leadership and organizational cultures, conducive to CQI success were evident. However, limitations in performance measurement and managerial discretion were key barriers.

CONCLUSION: The four dimensions of CQI provided insight into both facilitators and barriers of CQI adoption in public health. Future research should compare the outcomes of public health CQI initiatives to the framework's stated facilitators and barriers.}, } @article {pmid28260409, year = {2017}, author = {Barson, S and Doolan-Noble, F and Gray, J and Gauld, R}, title = {Healthcare leaders' views on successful quality improvement initiatives and context.}, journal = {Journal of health organization and management}, volume = {31}, number = {1}, pages = {54-63}, doi = {10.1108/JHOM-10-2016-0191}, pmid = {28260409}, issn = {1758-7247}, mesh = {Attitude of Health Personnel ; *Health Facility Administrators ; Humans ; Interviews as Topic ; Patient Participation/methods ; Program Development/methods ; Program Evaluation ; Quality Improvement/*organization & administration ; }, abstract = {Purpose The purpose of this paper is to investigate the contextual factors contributing to the sustainability of healthcare quality improvement (QI) initiatives. Design/methodology/approach Themes from semi-structured interviews with international healthcare leaders are compared with Kaplan and Provost et al.'s (2012) model for understanding success in quality (MUSIQ). Critical success factors within these themes are shown in detail. Findings The interviews provide a rich source of information on critical success factors. The themes largely correspond with MUSIQ, reinforcing its robustness. An important factor emerging from the interviews was the importance of engagement with patients and families in QI, and this needs consideration in seeking to understand context in QI. Research limitations/implications Interview participants represent a limited set of western countries and health systems. Their experiences may not hold true in other settings. Practical implications The detail on critical success factors provides QI practitioners with guidance on designing and implementing sustainable initiatives. Originality/value Including consideration of contextual factors for engagement with patients and families in frameworks for context in QI appears to be an original idea that will add value to such frameworks. Researchers in patient engagement are starting to address contextual factors and connections should be made with this work.}, } @article {pmid28259748, year = {2017}, author = {Borland, C and Hughes, JMB and Guénard, H}, title = {The blood transfer conductance for CO and NO.}, journal = {Respiratory physiology & neurobiology}, volume = {241}, number = {}, pages = {53-57}, doi = {10.1016/j.resp.2017.02.010}, pmid = {28259748}, issn = {1878-1519}, mesh = {Carbon Monoxide/*blood ; Humans ; Models, Cardiovascular ; Nitric Oxide/*blood ; Pulmonary Diffusing Capacity ; }, abstract = {Nitric oxide was introduced over 30 years ago as a test gas for alveolar capillary diffusion. As for CO its transfer has been interpreted according to the Roughton Forster relationship: 1/DL=1/DM+1/θVc. There has been disagreement, since the first measurements of DLNO, over whether θNO is infinite and thus DLNO=DMNO. There is overwhelming in vitro evidence that θNO is finite yet several groups (Coffman et al., 2017; Tamhane et al., 2001) use an infinite value in vivo. They also assume that DMNO is greater than twice DMCO, making DMCO less than that predicted by the physical laws of diffusion. Finally some (Coffman et al., 2017) recommend use of Reeve and Park's value for θCO (Reeves and Park, 1992; Coffman et al., 2017) rather than Forster's (Forster, 1987). Their grounds for doing so are that the combination of an infinite theta NO, an empirical value for DMNO/DMCO (>2.0) and Reeve and Park's θCO gives a value of DMCO (using a combined DLNO-DLCO analysis) which agrees with the DMCO value calculated separately by the classical two-stage oxygen technique of Roughton and Forster. In this paper we examine whether there are physiological reasons for assuming that DMNO is over twice DMCO in vivo. We are critical of Reeves and Park's estimate for the 1/θCO-PO2 relationship. We review in vitro estimates of θCO in the light of Guenard et al.'s recent in vivo estimate.}, } @article {pmid28254059, year = {2017}, author = {Xu, F and Jin, H and Ji, Z and Chen, J and Loh, PS}, title = {Sources and distribution of sedimentary organic matter along the northern Bering and Chukchi Seas.}, journal = {Journal of environmental sciences (China)}, volume = {52}, number = {}, pages = {66-75}, doi = {10.1016/j.jes.2016.04.003}, pmid = {28254059}, issn = {1001-0742}, mesh = {Arctic Regions ; Canada ; Climate Change ; *Environmental Monitoring ; Geologic Sediments/*analysis ; Lignin/analysis ; Phenols/analysis ; Seawater/*chemistry ; Water Pollutants, Chemical/*analysis ; }, abstract = {In this study, lignin-derived phenols were used to determine the sources and distribution of sedimentary organic matter along the northern Bering Sea and Chukchi Sea of the Arctic Ocean. The lignin parameter syringyl/vanillyl (S/V) and cinnamyl/vanillyl (C/V) ratios are used to indicate vegetation sources; and the ratios of vanillic acid/vanillin, (Ad/Al)v and syringic acid/syringaldehyde, (Ad/Al)s are used as indicators of lignin diagenesis. Results showed the predominance of woody gymnosperm signal at the easternmost location in the northern Bering Sea, a mixture of refractory non-woody angiosperm and fresher gymnosperm tissues in the Chukchi Sea, and signal of fresher woody gymnosperm tissues in the northernmost locations in the Chukchi Sea. The lignin materials showed gradual increase in decomposition stage during transport along the northern Bering Sea. Hydrodynamic sorting process, which is the retention of coarser materials nearshore and transportation of finer particles farther offshore, most probably occurred along the east coast of the northern Bering Sea. In Chukchi Sea, the non-woody angiosperm tissues could have originated from the Canadian Arctic and gymnosperm tissues could be from the Russian Arctic side. The fresher materials in the northernmost Chukchi Sea could have been transported here via the ice-rafting process. Detection of fresh lignin materials and the occurrence of lignin decomposition mean that this region could be sensitive to the impact of climate change.}, } @article {pmid28252837, year = {2017}, author = {Verloo, H and Desmedt, M and Morin, D}, title = {Adaptation and validation of the Evidence-Based Practice Belief and Implementation scales for French-speaking Swiss nurses and allied healthcare providers.}, journal = {Journal of clinical nursing}, volume = {26}, number = {17-18}, pages = {2735-2743}, doi = {10.1111/jocn.13786}, pmid = {28252837}, issn = {1365-2702}, mesh = {Adult ; Allied Health Personnel/*psychology ; Cross-Sectional Studies ; Evidence-Based Practice/*methods ; Factor Analysis, Statistical ; Female ; *Health Knowledge, Attitudes, Practice ; Humans ; Language ; Male ; Middle Aged ; Nurses/*psychology ; Psychometrics ; Reproducibility of Results ; Surveys and Questionnaires/*standards ; Young Adult ; }, abstract = {AIMS AND OBJECTIVES: To evaluate two psychometric properties of the French versions of the Evidence-Based Practice Beliefs and Evidence-Based Practice Implementation scales, namely their internal consistency and construct validity.

BACKGROUND: The Evidence-Based Practice Beliefs and Evidence-Based Practice Implementation scales developed by Melnyk et al. are recognised as valid, reliable instruments in English. However, no psychometric validation for their French versions existed.

DESIGN: Secondary analysis of a cross sectional survey.

METHODS: Source data came from a cross-sectional descriptive study sample of 382 nurses and other allied healthcare providers. Cronbach's alpha was used to evaluate internal consistency, and principal axis factor analysis and varimax rotation were computed to determine construct validity.

RESULTS: The French Evidence-Based Practice Beliefs and Evidence-Based Practice Implementation scales showed excellent reliability, with Cronbach's alphas close to the scores established by Melnyk et al.'s original versions. Principal axis factor analysis showed medium-to-high factor loading scores without obtaining collinearity. Principal axis factor analysis with varimax rotation of the 16-item Evidence-Based Practice Beliefs scale resulted in a four-factor loading structure. Principal axis factor analysis with varimax rotation of the 17-item Evidence-Based Practice Implementation scale revealed a two-factor loading structure. Further research should attempt to understand why the French Evidence-Based Practice Implementation scale showed a two-factor loading structure but Melnyk et al.'s original has only one.

CONCLUSION: The French versions of the Evidence-Based Practice Beliefs and Evidence-Based Practice Implementation scales can both be considered valid and reliable instruments for measuring Evidence-Based Practice beliefs and implementation.

The results suggest that the French Evidence-Based Practice Beliefs and Evidence-Based Practice Implementation scales are valid and reliable and can therefore be used to evaluate the effectiveness of organisational strategies aimed at increasing professionals' confidence in Evidence-Based Practice, supporting its use and implementation.}, } @article {pmid28243480, year = {2017}, author = {He, YC and Huang, P and Li, QQ and Sun, Q and Li, DH and Wang, T and Shen, JY and Du, JJ and Cui, SS and Gao, C and Fu, R and Chen, SD}, title = {Mutation Analysis of HTRA2 Gene in Chinese Familial Essential Tremor and Familial Parkinson's Disease.}, journal = {Parkinson's disease}, volume = {2017}, number = {}, pages = {3217474}, pmid = {28243480}, issn = {2090-8083}, abstract = {Background. HTRA2 has already been nominated as PARK13 which may cause Parkinson's disease, though there are still discrepancies among these results. Recently, Gulsuner et al.'s study found that HTRA2 p.G399S is responsible for hereditary essential tremor and homozygotes of this allele develop Parkinson's disease by examining a six-generation family segregating essential tremor and essential tremor coexisting with Parkinson's disease. We performed this study to validate the condition of HTRA2 gene in Chinese familial essential tremor and familial Parkinson's disease patients, especially essential tremor. Methods. We directly sequenced all eight exons, exon-intron boundaries, and part of the introns in 101 familial essential tremor patients, 105 familial Parkinson's disease patients, and 100 healthy controls. Results. No exonic variant was identified, while one exon-intron boundary variant (rs2241028) and one intron variant (rs2241027) were detected, both with no clinical significance and uncertain function. There was no difference in allele, genotype, and haplotype between groups. Conclusions. HTRA2 exonic variant might be rare among Chinese Parkinson's disease and essential tremor patients with family history, and HTRA2 may not be the cause of familial Parkinson's disease and essential tremor in China.}, } @article {pmid28243213, year = {2017}, author = {Gäde, JC and Schermelleh-Engel, K and Klein, AG}, title = {Disentangling the Common Variance of Perfectionistic Strivings and Perfectionistic Concerns: A Bifactor Model of Perfectionism.}, journal = {Frontiers in psychology}, volume = {8}, number = {}, pages = {160}, pmid = {28243213}, issn = {1664-1078}, abstract = {Perfectionism nowadays is frequently understood as a multidimensional personality trait with two higher-order dimensions of perfectionistic strivings and perfectionistic concerns. While perfectionistic concerns are robustly found to correlate with negative outcomes and psychological malfunctioning, findings concerning the outcomes of perfectionistic strivings are inconsistent. There is evidence that perfectionistic strivings relate to psychological maladjustment on the one hand but to positive outcomes on the other hand as well. Moreover, perfectionistic strivings and perfectionistic concerns frequently showed substantial overlap. These inconsistencies of differential relations and the substantial overlap of perfectionistic strivings and perfectionistic concerns raise questions concerning the factorial structure of perfectionism and the meaning of its dimensions. In this study, several bifactor models were applied to disentangle the common variance of perfectionistic strivings and perfectionistic concerns at the item level using Hill et al.'s (2004) Perfectionism Inventory (PI). The PI measures a broad range of perfectionism dimensions by four perfectionistic strivings and four perfectionistic concerns subscales. The bifactor-(S - 1) model with one general factor defined by concern over mistakes as the reference facet, four specific perfectionistic strivings factors, and three specific perfectionistic concerns factors showed acceptable fit. The results revealed a clear separation between perfectionistic strivings and perfectionistic concerns, as the general factor represented concern over mistakes, while the perfectionistic strivings factors each explained a substantial amount of reliable variance independent of the general factor. As a result, factor scores of the specific perfectionistic strivings factors and the general factor had differential relationships with achievement motivation, neuroticism, conscientiousness, and self-efficacy that met with theoretical expectations, while results for manifest subscale scores were ambiguous. Our results question the existence of reliable sub-constructs of perfectionistic concerns independent of the general factor when defined by concern over mistakes.}, } @article {pmid28239926, year = {2017}, author = {Gilbert, MT}, title = {Documenting DNA in the dust.}, journal = {Molecular ecology}, volume = {26}, number = {4}, pages = {969-971}, doi = {10.1111/mec.13944}, pmid = {28239926}, issn = {1365-294X}, mesh = {Allergens ; Animals ; *Arthropods ; DNA ; Dust/*analysis ; United States ; }, abstract = {I bought a robotic vacuum cleaner this summer and set it to work. Although my initial expectations were not high, my robot (christened Buddy) finished its cleaning cycle, and then insistently demanded that I empty its dust collection box. As I took the box out, my jaw dropped. I live in a modern house, we don't have pets, and I like to think that I keep it reasonably dust free. But, there was much dust in that box. And when I ran it again 2 days later, the same thing happened. And indeed, every 2 days, Buddy dutifully goes to work, and sucks up a similarly impressive quantity. It's remarkable, and naturally begs the question of where it all comes from? Some is externally derived, entering the house with us or through open windows. Some is clearly fibres shed from clothes, furniture etc. Then there's the skin cells and hair we shed. But at least part is derived from the host of smaller organisms that live in and around our homes, many of which are arthropods (Butte & Heinzow). I suspect almost all readers are aware that some smaller animals live in our houses - even those who live in the modern urban houses will have occasionally encountered the odd drosophila, silverfish or spider. But I suspect that prior to reading Madden et al.'s article in this issue of Molecular Ecology (Madden et al.), few of you will have appreciated the true diversity, which, it turns out, is huge.}, } @article {pmid28231801, year = {2017}, author = {Bunger, AC and Powell, BJ and Robertson, HA and MacDowell, H and Birken, SA and Shea, C}, title = {Tracking implementation strategies: a description of a practical approach and early findings.}, journal = {Health research policy and systems}, volume = {15}, number = {1}, pages = {15}, pmid = {28231801}, issn = {1478-4505}, support = {K01 MH113806/MH/NIMH NIH HHS/United States ; L30 MH108060/MH/NIMH NIH HHS/United States ; R25 MH080916/MH/NIMH NIH HHS/United States ; TL1 TR000111/TR/NCATS NIH HHS/United States ; }, mesh = {Data Collection ; *Diffusion of Innovation ; Group Processes ; Humans ; Leadership ; Organizational Innovation ; *Program Development ; Prospective Studies ; Research/organization & administration ; Research Personnel/organization & administration ; Retrospective Studies ; }, abstract = {BACKGROUND: Published descriptions of implementation strategies often lack precision and consistency, limiting replicability and slowing accumulation of knowledge. Recent publication guidelines for implementation strategies call for improved description of the activities, dose, rationale and expected outcome(s) of strategies. However, capturing implementation strategies with this level of detail can be challenging, as responsibility for implementation is often diffuse and strategies may be flexibly applied as barriers and challenges emerge. We describe and demonstrate the development and application of a practical approach to identifying implementation strategies used in research and practice that could be used to guide their description and specification.

METHODS: An approach to tracking implementation strategies using activity logs completed by project personnel was developed to facilitate identification of discrete strategies. This approach was piloted in the context of a multi-component project to improve children's access to behavioural health services in a county-based child welfare agency. Key project personnel completed monthly activity logs that gathered data on strategies used over 17 months. Logs collected information about implementation activities, intent, duration and individuals involved. Using a consensus approach, two sets of coders categorised each activity based upon Powell et al.'s (Med Care Res Rev 69:123-57, 2012) taxonomy of implementation strategies.

RESULTS: Participants reported on 473 activities, which represent 45 unique strategies. Initial implementation was characterised by planning strategies followed by educational strategies. After project launch, quality management strategies predominated, suggesting a progression of implementation over time. Together, these strategies accounted for 1594 person-hours, many of which were reported by the leadership team that was responsible for project design, implementation and oversight.

CONCLUSIONS: This approach allows for identifying discrete implementation strategies used over time, estimating dose, describing temporal ordering of implementation strategies, and pinpointing the major implementation actors. This detail could facilitate clear reporting of a full range of implementation strategies, including those that may be less observable. This approach could lead to a more nuanced understanding of what it takes to implement different innovations, the types of strategies that are most useful during specific phases of implementation, and how implementation strategies need to be adaptively applied throughout the course of a given initiative.}, } @article {pmid28231389, year = {2017}, author = {Renton, K and Low, A}, title = {Response: Slykerman et al.'s antibiotics in the first year of life and subsequent neurocognitive outcome.}, journal = {Acta paediatrica (Oslo, Norway : 1992)}, volume = {106}, number = {6}, pages = {1009}, doi = {10.1111/apa.13795}, pmid = {28231389}, issn = {1651-2227}, mesh = {Anti-Bacterial Agents/*therapeutic use ; Cognition/*drug effects ; Humans ; Infant ; Infant, Newborn ; }, } @article {pmid28230414, year = {2017}, author = {Friborg, O and Johnsen, TJ}, title = {The effect of cognitive-behavioral therapy as an antidepressive treatment is falling: Reply to Ljòtsson et al. (2017) and Cristea et al. (2017).}, journal = {Psychological bulletin}, volume = {143}, number = {3}, pages = {341-345}, doi = {10.1037/bul0000090}, pmid = {28230414}, issn = {1939-1455}, mesh = {*Accidental Falls ; Cognition ; *Cognitive Behavioral Therapy ; Depressive Disorder, Major ; Humans ; Psychiatric Status Rating Scales ; }, abstract = {This article critically reassesses the nonlinear reanalysis by Ljótsson, Hedman, Mattsson, and Andersson (2017) and reviews Cristea et al.'s (2017) extension of our original meta-analysis (Johnsen & Friborg, 2015) reporting a decline in the effects of cognitive-behavioral therapy (CBT) for treating unipolar depression. Ljótsson et al. fitted a piecewise meta-regression model to the data, indicating a halt in the decline from the year 1995 onward, hence concluding that CBT is not gradually losing its efficacy. We reanalyzed the data for nonlinear time trends and replicated their findings for the 34 studies using the Hamilton Rating Scale for Depression as the outcome but not for the 67 studies using Beck's Depression Inventory as the outcome. The best nonlinear model was quadratic rather than flat (or linear) from 2001 onward, which opposes the conclusion by Ljótsson et al. of stability in effects. Cristea et al. identified additional studies, but their new analyses provided mixed support for a linear decline in CBT effects. They could not dismiss a decline except only in the most stringent analytic condition-namely, when analyzing only 29 randomized controlled trials based on between-groups effect sizes solely. Their study includes several questionable methodological choices, so we expand on the discussion of these disparate meta-analytic findings. Of particular concern is the tendency to downplay the fact that when looking at all of the studies together, there is a clear decline in the effects of CBT, which should concern therapy researchers within the field rather than being explained away. (PsycINFO Database Record}, } @article {pmid28229016, year = {2016}, author = {O'Neill, HK and McLean, AJ and Kalis, R and Shultz, JM}, title = {Disaster averted: Community resilience in the face of a catastrophic flood.}, journal = {Disaster health}, volume = {3}, number = {3}, pages = {67-77}, pmid = {28229016}, issn = {2166-5044}, abstract = {In the spring of 2009, the Fargo, North Dakota, metropolitan area had 5 days to lay millions of sandbags to avoid devastation from record flooding of the Red River of the North. The community was able to successfully mitigate the flooding and escape potentially catastrophic economic, physical, and mental health consequences. We hypothesized that Fargo flood protection efforts reflected the community resilience factors proposed by Norris, Stevens, Pfefferbaum, et al. (2008): citizen involvement in mitigation efforts, effective organizational linkages, ongoing psychosocial support, and strong civic leadership in the face of rapidly changing circumstances. This community case report utilizes an extensive review of available sources, including news reports, government documents, research articles, and personal communication. Results demonstrate that Fargo's response to the threat of catastrophic flooding was consistent with Norris et al.'s (2008) factors of community resilience. Furthermore, success in 2009 carried over into future flood prevention and response efforts, as well as a structured approach to building psychological resilience. This case study contributes to the literature on community resilience by describing a community's successful efforts to avert a potentially catastrophic disaster.}, } @article {pmid28224281, year = {2017}, author = {Mlynski, R}, title = {Reply to Wimmer et al.'s comments concerning: 'off the ear with no loss in speech understanding: comparing the RONDO and the OPUS 2 cochlear implant audio processors'.}, journal = {European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery}, volume = {274}, number = {8}, pages = {3263}, pmid = {28224281}, issn = {1434-4726}, } @article {pmid28217012, year = {2017}, author = {Oliveira, JM and Gomes, C and Faria, DB and Vieira, TS and Silva, FA and Vale, J and Pimentel, FL}, title = {[68]Ga-prostate-specific Membrane Antigen Positron Emission Tomography/Computed Tomography for Prostate Cancer Imaging: A Narrative Literature Review.}, journal = {World journal of nuclear medicine}, volume = {16}, number = {1}, pages = {3-7}, pmid = {28217012}, issn = {1450-1147}, abstract = {The [68]Ga-prostate-specific membrane antigen ([68]Ga-PSMA) has been recently developed to be used, as a ligand, in positron emission tomography/computed tomography (PET/CT) prostate cancer imaging, to detect prostate disease. The main objective of this review was to collect data and findings from other studies and articles to assess, theoretically, if [68]GA-PSMA PET/CT is a more appropriate prostate cancer diagnostic technique in comparison with others available such as CT, [18]F-fluoro-2-deoxyglucose PET/CT, or [18]F-fluoromethylcholine ([18]F-choline) PET/CT. For that purpose, PubMed, the online scientific articles' database, was consulted where the keywords "PSMA" and "PET" were used to find relevant articles. The clinicaltrials.gov, clinical trials' database, was also consulted where the keywords "[68]Ga-PSMA" and "prostate" were used to search clinical trials. Based on the reviewed scientific literature, several studies were conducted to assess and compare the [68]Ga-PSMA PET/CT detection rate in prostate cancer with other available techniques. One of those studies, conducted by Giesel et al., concluded, within study sample, that 75% of patients with lymph nodes detected by [68]Ga-PSMA PET/CT would have not been identified using other conventional morphological criteria based techniques. In Eiber et al.'s study, [68]Ga-PSMA PET detected prostatic disease findings in 67% of patients with prostate-specific antigen levels <1 ng/mL, when compared with choline-based PET that presented detection rates between 19% and 36%. In Bluemel et al.'s study, [68]Ga-PSMA identified positive prostatic disease in 43.8% of the patients with negative findings in F-choline PET/CT. Findings from this review demonstrate that [68]Ga-PSMA PET/C is more effective in detecting metastases, lymph nodes, and recurrent prostate cancer when compared to [18]F-choline-based PET/CT and CT. [68]Ga-PSMA PET/CT presents also more imaging contrast and can be more cost-effective. [68]Ga-PSMA has already been subjected to first-in-human trials, and it is now being tested in Phase II and III trials.}, } @article {pmid28213709, year = {2017}, author = {Dou, R and Zhang, J and Chen, Y and Feng, S}, title = {High efficiency removal of triclosan by structure-directing agent modified mesoporous MIL-53(Al).}, journal = {Environmental science and pollution research international}, volume = {24}, number = {9}, pages = {8778-8789}, pmid = {28213709}, issn = {1614-7499}, mesh = {Adsorption ; Charcoal/chemistry ; Coordination Complexes/*chemistry ; Hydrogen-Ion Concentration ; Osmolar Concentration ; Porosity ; Spectroscopy, Fourier Transform Infrared ; Structure-Activity Relationship ; Surface Properties ; Thermodynamics ; Triclosan/*analysis/chemistry ; Water Pollutants, Chemical/*analysis/chemistry ; Water Purification/*methods ; }, abstract = {In order to expand the potential applications of metal-organic frameworks (MOFs), structure directing agents modified mesoporous MIL-53(Al) (MIL-53(Al)-1) was investigated to adsorb triclosan (TCS) with two different initial concentrations. MIL-53(Al)-1 with high mesoporosity and total pore volume exhibited higher adsorption capacity and 4.4 times faster adsorption of TCS at low concentration (1 mg L[-1]) than that of microporous MIL-53(Al). Also, mesoporous as well as microporous MIL-53(Al) showed significant higher adsorption capacity and two orders of magnitude greater fast uptake of TCS than two kinds of mesoporous-activated carbon. The adsorption of TCS onto MIL-53(Al)-1 released more energy and had higher disorderliness than TCS on MIL-53(Al). The superior adsorption characteristics of MIL-53(Al)-1 were preserved over a wide pH range (4-9), at high concentration of ionic strengths, and in the presence of coexisting compounds (anions, cations, phenol, aniline, and humic acid). The selectivity adsorption and Fourier transform infrared (FT-IR) spectra revealed that TCS adsorption on MIL-53(Al)s was mainly driven by hydrophobicity interaction assisted with hydrogen bonding on MIL-53(Al)s. MIL-53(Al)s can be effectively regenerated several times by washing with 90% methanol-water (pH 11). All of the above results demonstrated MIL-53(Al)s are promising adsorbents for water purification. Graphical abstract.}, } @article {pmid28202233, year = {2018}, author = {Abuzour, AS and Lewis, PJ and Tully, MP}, title = {Practice makes perfect: A systematic review of the expertise development of pharmacist and nurse independent prescribers in the United Kingdom.}, journal = {Research in social & administrative pharmacy : RSAP}, volume = {14}, number = {1}, pages = {6-17}, doi = {10.1016/j.sapharm.2017.02.002}, pmid = {28202233}, issn = {1934-8150}, mesh = {Clinical Competence ; Drug Prescriptions ; Health Knowledge, Attitudes, Practice ; Humans ; *Models, Theoretical ; Nurse's Role ; Nurses/*organization & administration ; Pharmaceutical Services/organization & administration ; Pharmacists/*organization & administration ; Professional Role ; United Kingdom ; }, abstract = {BACKGROUND: Prescribing is a complex and error-prone task that demands expertise. McLellan et al.'s theory of expertise development model ("the model"), developed to assess medical literature on prescribing by medical students, proposes that in order to develop, individuals should deliberately engage their knowledge, skills and attitudes within a social context. Its applicability to independent prescribers (IP) is unknown.

AIM: A systematic review was conducted to explore whether the model is applicable to non-medical independent prescribing and to assess the factors underpinning expertise development reported in the literature.

METHOD: Six electronic databases (EMBASE, Medline, AMED, CINAHL, IPA and PsychInfo) were searched for articles published between 2006 and 2016, reporting empirical data on pharmacist and nurse IPs education or practice. Data were extracted using themes from the model and analysed using framework analysis.

RESULTS: Thirty-four studies met the inclusion criteria. Knowledge, pre-registration education, experience, support and confidence were some of the intrinsic and extrinsic factors influencing IPs. Difficulty in transferring theory to practice was attributed to lack of basic pharmacology and bioscience content in pre-registration nursing rather than the prescribing programme. Students saw interventions using virtual learning or learning in practice as more useful with long-term benefits e.g. students were able to use their skills in history taking following the virtual learning intervention 6-months after the programme. All studies demonstrated how engaging knowledge and skills affected individuals' attitude by, for example, increasing professional dignity. IPs were able to develop their expertise when integrating their competencies in a workplace context with support from colleagues and adherence to guidelines.

CONCLUSION: This is the first study to synthesize data systematically on expertise development from studies on IPs using the model. The model showed the need for stronger foundations in scientific knowledge amongst some IPs, where continuous workplace practice can improve skills and strengthen attitudes. This could facilitate a smoother transfer of learnt theory to practice, in order for IPs to be experts within their fields and not merely adequately competent.}, } @article {pmid28201989, year = {2017}, author = {Molina-Venegas, R and Rodríguez, MÁ}, title = {Revisiting phylogenetic signal; strong or negligible impacts of polytomies and branch length information?.}, journal = {BMC evolutionary biology}, volume = {17}, number = {1}, pages = {53}, pmid = {28201989}, issn = {1471-2148}, mesh = {*Biological Evolution ; Models, Genetic ; *Phylogeny ; }, abstract = {BACKGROUND: Inaccurate estimates of phylogenetic signal may mislead interpretations of many ecological and evolutionary processes, and hence understanding where potential sources of uncertainty may lay has become a priority for comparative studies. Importantly, the sensitivity of phylogenetic signal indices and their associated statistical tests to incompletely resolved phylogenies and suboptimal branch-length information has been only partially investigated. METHODS: Here, we use simulations of trait evolution along phylogenetic trees to assess whether incompletely resolved phylogenies (polytomic chronograms) and phylogenies with suboptimal branch-length information (pseudo-chronograms) could produce directional biases in significance tests (p-values) associated with Blomberg et al.'s K and Pagel's lambda (λ) statistics, two of the most widely used indices to measure and test phylogenetic signal. Specifically, we conducted pairwise comparisons between the p-values resulted from the use of "true" chronograms and their degraded counterparts (i.e. polytomic chronograms and pseudo-chronograms), and computed the frequency with which the null hypothesis of no phylogenetic signal was accepted using "true" chronograms but rejected when using their degraded counterparts (type I bias) and vice versa (type II bias).

RESULTS: We found that the use of polytomic chronograms in combination with Blomberg et al.'s K resulted in both, clearly inflated estimates of phylogenetic signal and moderate levels of type I and II biases. More importantly, pseudo-chronograms led to high rates of type I biases. In contrast, Pagel's λ was strongly robust to either incompletely resolved phylogenies and suboptimal branch-length information.

CONCLUSIONS: Our results suggest that pseudo-chronograms can lead to strong overestimation of phylogenetic signal when using Blomberg et al.'s K (i.e. high rates of type I biases), while polytomies may be a minor concern given other sources of uncertainty. In contrast, Pagel's λ seems strongly robust to either incompletely resolved phylogenies and suboptimal branch-length information. Hence, Pagel's λ may be a more appropriate alternative over Blomberg et al.'s K to measure and test phylogenetic signal in most ecologically relevant traits when phylogenetic information is incomplete.}, } @article {pmid28199512, year = {2017}, author = {Schätzle, M and Zinelis, S and Markic, G and Eliades, G and Eliades, T}, title = {Structural, morphological, compositional, and mechanical changes of palatal implants after use: a retrieval analysis.}, journal = {European journal of orthodontics}, volume = {39}, number = {6}, pages = {579-585}, doi = {10.1093/ejo/cjx001}, pmid = {28199512}, issn = {1460-2210}, mesh = {Bone-Implant Interface ; *Dental Implants ; Humans ; Materials Testing/methods ; Microscopy, Electron, Scanning ; Orthodontic Anchorage Procedures/*instrumentation ; Orthodontic Appliance Design ; Osseointegration ; Surface Properties ; Titanium/chemistry ; }, abstract = {PURPOSE: The aim of this study was to characterize the surface, elemental, and mechanical alterations of orthodontic palatal implants after intraoral aging.

MATERIALS AND METHOD: Nineteen consecutively retrieved implants (RET) after orthodontic treatment and three unused implants used as control (CON) were included in this study. Both groups were characterized non-destructively by Stereomicroscopy, Optical Profilometry (Sa, Sq, Sz, Sc), and SEM/EDX analysis and then destructively after metallogaphic preparation employing instrumented indentation testing (HM, EIT, ηIT, and HV) and SEM/EDX at bone-implant interface.

RESULTS: All retrieved implants showed a loss of gloss with the formation of bone-like formation on the majority of them. However, no differences in surface roughness parameters were identified between macroscopically intact and retrieved regions of implants. The elements precipitated on the surface were O, C, Ca, and P while traces of Na, K, Al, S, Cl, and Mg were also identified. The surface of control sample is characterized by small pits while only Ti and Al traces were identified by EDX analysis. The presence of all the aforementioned elements apart from Ti and Al on the retrieved implants' surface should be appended to the contact of implant with bone and biological fluids while Interfacial analysis revealed a well-formed bone-implant interface. However, no significant differences were found for all mechanical properties tested between RET and CON groups.

CONCLUSIONS: The results of this study indicate that retrieved palatal implant surface has undergone morphological and elemental alterations probably associated with the osseointegration process during service. Insertion and functional loading did not affect the mechanical properties of implants tested.}, } @article {pmid28191987, year = {2017}, author = {Collier, ES and Lawson, R}, title = {It's out of my hands! Grasping capacity may not influence perceived object size.}, journal = {Journal of experimental psychology. Human perception and performance}, volume = {43}, number = {4}, pages = {749-769}, pmid = {28191987}, issn = {1939-1277}, mesh = {Adult ; Female ; Functional Laterality/*physiology ; Hand/*physiology ; Humans ; Male ; Motor Activity/*physiology ; Size Perception/*physiology ; Visual Perception/*physiology ; Young Adult ; }, abstract = {Linkenauger, Witt, and Proffitt (2011) found that the perceived size of graspable objects was scaled by perceived grasping capacity. However, it is possible that this effect occurred because object size was estimated on the same trial as grasping capacity. This may have led to a conflation of estimates of perceived action capacity and spatial properties. In 5 experiments, we tested Linkenauger et al.'s claim that right-handed observers overestimate the grasping capacity of their right hand relative to their left hand, and that this, in turn, leads them to underestimate the size of objects to-be-grasped in their right hand relative to their left hand. We replicated the finding that right handers overestimate the size and grasping capacity of their right hand relative to their left hand. However, when estimates of object size and grasping capacity were made in separate tasks, objects grasped in the right hand were not underestimated relative to those grasped in the left hand. Further, when grasping capacity was physically restricted, observers appropriately recalibrated their perception of their maximum grasp but estimates of object size were unaffected. Our results suggest that changes in action capacity may not influence perceived object size if sources of conflation are controlled for. (PsycINFO Database Record}, } @article {pmid28188199, year = {2017}, author = {Kilgas, MA and Elmer, SJ}, title = {Back to the future! Revisiting the physiological cost of negative work as a team-based activity for exercise physiology students.}, journal = {Advances in physiology education}, volume = {41}, number = {1}, pages = {120-129}, doi = {10.1152/advan.00158.2016}, pmid = {28188199}, issn = {1522-1229}, mesh = {Exercise/*physiology ; Exercise Test/*methods ; Forecasting ; Humans ; Muscle Contraction/physiology ; Muscle, Skeletal/physiology ; Physiology/*education ; Problem-Based Learning/*methods ; *Students, Health Occupations ; Surveys and Questionnaires ; }, abstract = {We implemented a team-based activity in our exercise physiology teaching laboratory that was inspired from Abbott et al.'s classic 1952 Journal of Physiology paper titled "The physiological cost of negative work." Abbott et al. connected two bicycles via one chain. One person cycled forward (muscle shortening contractions, positive work) while the other resisted the reverse moving pedals (muscle lengthening contractions, negative work), and the cost of work was compared. This study was the first to link human whole body energetics with isolated muscle force-velocity characteristics. The laboratory activity for our students (n = 35) was designed to reenact Abbott et al.'s experiment, integrate previously learned techniques, and illustrate differences in physiological responses to muscle shortening and lengthening contractions. Students (11-12 students/laboratory section) were split into two teams (positive work vs. negative work). One student from each team volunteered to cycle against the other for ~10 min. The remaining students in each team were tasked with measuring: 1) O2 consumption, 2) heart rate, 3) blood lactate, and 4) perceived exertion. Students discovered that O2 consumption during negative work was about one-half that of positive work and all other physiological parameters were also substantially lower. Muscle lengthening contractions were discussed and applied to rehabilitation and sport training. The majority of students (>90%) agreed or strongly agreed that they stayed engaged during the activity and it improved their understanding of exercise physiology. All students recommended the activity be performed again. This activity was engaging, emphasized teamwork, yielded clear results, was well received, and preserved the history of classic physiological experiments.}, } @article {pmid28182672, year = {2017}, author = {Jiang, DQ and Wang, Y and Zhou, D}, title = {Phenotypic equilibrium as probabilistic convergence in multi-phenotype cell population dynamics.}, journal = {PloS one}, volume = {12}, number = {2}, pages = {e0170916}, pmid = {28182672}, issn = {1932-6203}, mesh = {Evolution, Molecular ; *Models, Genetic ; *Phenotype ; Probability ; }, abstract = {We consider the cell population dynamics with n different phenotypes. Both the Markovian branching process model (stochastic model) and the ordinary differential equation (ODE) system model (deterministic model) are presented, and exploited to investigate the dynamics of the phenotypic proportions. We will prove that in both models, these proportions will tend to constants regardless of initial population states ("phenotypic equilibrium") under weak conditions, which explains the experimental phenomenon in Gupta et al.'s paper. We also prove that Gupta et al.'s explanation is the ODE model under a special assumption. As an application, we will give sufficient and necessary conditions under which the proportion of one phenotype tends to 0 (die out) or 1 (dominate). We also extend our results to non-Markovian cases.}, } @article {pmid28181095, year = {2017}, author = {Cheng, Q and Zhang, X and Ma, J}, title = {ICASME: An Improved Cloud-Based Authentication Scheme for Medical Environment.}, journal = {Journal of medical systems}, volume = {41}, number = {3}, pages = {44}, pmid = {28181095}, issn = {1573-689X}, mesh = {Computer Security/*instrumentation ; *Confidentiality ; Humans ; Information Systems/*instrumentation ; Telemedicine/*instrumentation ; }, abstract = {Unlike the traditional medical system, telecare medicine information system (TMIS) ensures that patients can get health-care services via the Internet at home. Authenticated key agreement protocol is very important for protecting the security in TMIS. Recently scholars have proposed a lot of authenticated key agreement protocols. In 2016, Chiou et al. demonstrated that Chen et al.'s authentication scheme fails to provide user's anonymity and message authentication and then proposed an enhanced scheme (Chiou et al., J. Med. Syst. 40(4):1-15, 2006) to overcome these drawbacks. In this paper, we demonstrate that Chiou et al.'s scheme is defenseless against key compromise impersonation (KCI) attack and also fails to provide forward security. Moreover, we propose a novel authentication scheme namely ICASME to overcome the mentioned weaknesses in this paper. Security analyses show that ICASME achieves the forward security and KCI attack resistance. In addition, it is proved that the time taken to implement the ICASME is not intolerable compared to the original protocol.}, } @article {pmid28176214, year = {2017}, author = {Ahn, J and Patel, TN and Buetti, S and Lleras, A}, title = {Exploring the contributions of spatial and non-spatial working memory to priming of pop-out.}, journal = {Attention, perception & psychophysics}, volume = {79}, number = {4}, pages = {1012-1026}, doi = {10.3758/s13414-017-1285-x}, pmid = {28176214}, issn = {1943-393X}, mesh = {Adult ; Attention/*physiology ; Color Perception/physiology ; Female ; Humans ; Memory, Short-Term/*physiology ; Pattern Recognition, Visual/*physiology ; Psychomotor Performance/*physiology ; Random Allocation ; Reaction Time/*physiology ; Space Perception/*physiology ; Young Adult ; }, abstract = {Priming of pop-out (PoP) refers to the facilitation of performance that occurs when a target-defining feature is repeated across consecutive trials in a pop-out oddball search task. The underlying mechanism of PoP has been poorly understood and raises important questions about how our visual system is guided by past experiences, even during bottom-up processing. Lee, Mozer, and Vecera (Attention, Perception, & Psychophysics, 71, 1059-1071, 2009) demonstrated that PoP remained unaffected by a concurrent non-spatial visual working memory (VWM) load, and they concluded that PoP occurs through feature gain modulation, essentially eliminating the contribution of memory representations in VWM to PoP. In the present study, we followed up on those results by (a) replicating the null effect of non-spatial VWM load on PoP and (b) examining the effect of spatial VWM load on PoP. The results showed that spatial VWM load does interfere with PoP, supporting the notion that spatial VWM is involved in PoP. In Experiment 2, we extended this finding by manipulating VWM load and observing its consequence on the magnitude of PoP. Increasing spatial VWM load decreased the amount of PoP observed, in a dose-dependent manner, whereas changes in non-spatial VWM load did not. Contrary to Lee et al.'s conclusions, these results suggest that VWM resources appear to contribute to the occurrence of PoP, supporting the theory that PoP is, in fact, a multilevel process in which the deployment of spatial attention, relying on VWM representations, plays an important role.}, } @article {pmid28170123, year = {2017}, author = {Ingiliz, P}, title = {Editorial to Martinello et al.'s HCV reinfection incidence among individuals treated for recent infection.}, journal = {Journal of viral hepatitis}, volume = {24}, number = {5}, pages = {357-358}, doi = {10.1111/jvh.12686}, pmid = {28170123}, issn = {1365-2893}, mesh = {*HIV Infections ; Hepacivirus ; *Hepatitis C ; Homosexuality, Male ; Humans ; Incidence ; Male ; Risk-Taking ; Substance Abuse, Intravenous/epidemiology ; }, abstract = {Reinfections with the hepatitis C virus have been described in subgroups with ongoing risk-behaviour, in particular in people who infect drugs (PWID) or men who have sex with men (MSM). In this article by Martinello and colleagues describe a reinfection incidence of 7.4 per 100 person years (95% CI 4.0-13.8), mainly in HIV-infected MSM who are also injecting drug users. A specific risk behavious counselling is mandatory in this setting.}, } @article {pmid28168714, year = {2017}, author = {Isa, MI and Hefner, JT and Markey, MA}, title = {Application of the Stephan et al. Chest Radiograph Comparison Method to Decomposed Human Remains.}, journal = {Journal of forensic sciences}, volume = {62}, number = {5}, pages = {1304-1307}, doi = {10.1111/1556-4029.13432}, pmid = {28168714}, issn = {1556-4029}, mesh = {Body Remains ; Cervical Vertebrae/*diagnostic imaging ; Clavicle/*diagnostic imaging ; Forensic Anthropology/*methods ; Humans ; Thoracic Vertebrae/*diagnostic imaging ; }, abstract = {This manuscript describes the use of comparative radiography of the chest to facilitate positive identification of human remains in advanced stages of decomposition. The method reported by Stephan et al. for positive identification of dry, disarticulated skeletal elements was used on semifleshed, decomposing remains. Positive identification was established through multiple points of concordance observed in radiographs of the left and right clavicles and the C5-T1 vertebrae. This case study demonstrates the applicability of the Stephan et al.'s method in cases involving decomposing remains.}, } @article {pmid28140451, year = {2017}, author = {Currell, MJ}, title = {Reply to Harrington et al.'s Comment on "Drawdown 'Triggers': A Misguided Strategy for Protecting Groundwater-Fed Streams and Springs," by Matthew J. Currell, 2016, v. 54, no. 5: 619-622.}, journal = {Ground water}, volume = {55}, number = {2}, pages = {154}, doi = {10.1111/gwat.12502}, pmid = {28140451}, issn = {1745-6584}, mesh = {*Groundwater ; Natural Springs ; *Rivers ; Water Movements ; }, } @article {pmid28133549, year = {2017}, author = {Usa, H and Matsumura, M and Ichikawa, K and Takei, H}, title = {A Maximum Muscle Strength Prediction Formula Using Theoretical Grade 3 Muscle Strength Value in Daniels et al.'s Manual Muscle Test, in Consideration of Age: An Investigation of Hip and Knee Joint Flexion and Extension.}, journal = {Rehabilitation research and practice}, volume = {2017}, number = {}, pages = {3985283}, pmid = {28133549}, issn = {2090-2867}, abstract = {This study attempted to develop a formula for predicting maximum muscle strength value for young, middle-aged, and elderly adults using theoretical Grade 3 muscle strength value (moment fair: Mf)-the static muscular moment to support a limb segment against gravity-from the manual muscle test by Daniels et al. A total of 130 healthy Japanese individuals divided by age group performed isometric muscle contractions at maximum effort for various movements of hip joint flexion and extension and knee joint flexion and extension, and the accompanying resisting force was measured and maximum muscle strength value (moment max, Mm) was calculated. Body weight and limb segment length (thigh and lower leg length) were measured, and Mf was calculated using anthropometric measures and theoretical calculation. There was a linear correlation between Mf and Mm in each of the four movement types in all groups, excepting knee flexion in elderly. However, the formula for predicting maximum muscle strength was not sufficiently compatible in middle-aged and elderly adults, suggesting that the formula obtained in this study is applicable in young adults only.}, } @article {pmid28129085, year = {2017}, author = {Haslam, N}, title = {More human than others? A critique of Cypryańska et al. (2017).}, journal = {The Journal of social psychology}, volume = {157}, number = {2}, pages = {143-147}, doi = {10.1080/00224545.2017.1282850}, pmid = {28129085}, issn = {1940-1183}, abstract = {Cypryańska and colleagues offer a critique of existing work on the self-humanizing effect and present some empirical findings motivated by their critique. In this commentary, I question their overly restrictive understanding of self-humanizing and argue that the phenomenon does not stand or fall on a definition based on a strict analogy to the better-than-average effect. I argue that defining self-humanizing exclusively in these terms is inappropriate: It fails to recognize the relationship between self-humanizing and self-enhancement, as well as the primary role of trait valence in comparative self-ratings. Finally, I observe that Cypryańska et al.'s empirical findings are highly consistent with past work rather than offering the deep challenge that the authors suppose.}, } @article {pmid28124590, year = {2017}, author = {Gomiero, T and Bertelli, M and Deb, S and Weger, E and Marangoni, A and De Bastiani, E and Mantesso, U and De Vreese, LP}, title = {A Multicentre Italian Validation Study in Aging Adults with Down Syndrome and Other Forms of Intellectual Disabilities: Dementia Screening Questionnaire for Individuals with Intellectual Disabilities.}, journal = {Current Alzheimer research}, volume = {14}, number = {7}, pages = {709-721}, doi = {10.2174/1567205014666170117094757}, pmid = {28124590}, issn = {1875-5828}, mesh = {Activities of Daily Living ; Adult ; Aged ; Aged, 80 and over ; Cohort Studies ; Dementia/*diagnosis/*etiology/psychology ; Down Syndrome/*complications/psychology ; Female ; Humans ; Intellectual Disability/*complications/psychology ; Italy ; Male ; Middle Aged ; *Psychometrics ; Reproducibility of Results ; Severity of Illness Index ; *Surveys and Questionnaires ; Translating ; }, abstract = {BACKGROUND: The USA National Task Group (NTG) guidelines advocate the use of an adapted version of Dementia Screening Questionnaire for Individuals with Intellectual Disabilities (DSQIID) for dementia screening of individuals with Down syndrome (DS) and with other forms of ID (non-DS).

OBJECTIVE: In order to meet these guidelines, this study verifies the psychometric properties of an Italian version of the original DSQIID in a population composed of adults aged 40 years and over with DS and non-DS ID.

METHODS: Internal consistency, inter-rater and intra-rater reliabilities, structural validity, convergent validity and known group differences of DSQIID-I were assessed with 200 individuals with ID (mean of 55.2 years; range: 40-80 years) recruited from 15 different centers in Italy. Diagnosis of dementia was done according to IASSID diagnostic criteria and its degree of clinical certainty was defined according to Silverman et al.'s classification (2004).

RESULTS: Cronbach's alpha for the DSQIID-I was 0.94. The ICCs for inter-rater and test-retest reliability were both 0.89. A Principal Component analysis revealed three domains, namely memory and confusion- related items, motor and functional disabilities, depression and apathy, which explained almost 40% of the overall variance. The total DSQIID-I score correlated significantly with DMR and differed significantly among those individuals (n = 34) with cognitive decline from those without (n = 166). Age, gender and severity of ID were unrelated to the DSQIID-I.

CONCLUSION: The present study confirms the cross-cultural value of DSQIID which was proved to be a psychometrically valid and user-friendly observer-rated scale for dementia screening in adults with both DS and non-DS ID.}, } @article {pmid28113172, year = {2016}, author = {Liu, YF and Guo, JM}, title = {Clustered-Dot Screen Design for Digital Multitoning.}, journal = {IEEE transactions on image processing : a publication of the IEEE Signal Processing Society}, volume = {25}, number = {7}, pages = {2971-2982}, doi = {10.1109/TIP.2016.2552723}, pmid = {28113172}, issn = {1941-0042}, abstract = {Digital multitoning is an extension of halftoning for rendering more than two tones at each pixel for higher image quality. Although a lot of effort has been put in generating dispersed dots previously, the blue-noise feature can hardly be achieved for those printers utilizing the electrophotography (EP) process to avoid the physically unstable isolated dots. To overcome this issue, Chandu et al. proposed a screening method for yielding green-noise dot clusters, yet noisy multitone texture was accompanied. This degrades the visual quality and the stability of tone rendering. In this paper, a significantly improved homogeneity of clustered dots can be achieved by the proposed screening method based upon the new inter-iterative clustered-dot direct multi-bit search algorithm. Compared with the former approaches, the inter-iteration design leads to less error by the updated initial multitone patterns. As demonstrated in the experimental results, both of the high homogenous multitone texture and less noisy perception at all absorptance levels are offered in contrast to the former Chandu et al.'s results. The high-quality output proves it as a very competitive candidate for EP printers, e.g., laser printers.}, } @article {pmid28111396, year = {2017}, author = {Furuya, K and Akiyama, S and Nambu, A and Suzuki, Y and Hasebe, Y}, title = {[A Method for the Automatic Exposure Control in Pediatric Abdominal CT: Application to the Standard Deviation Value and Tube Current Methods by Using Patient's Age and Body Size].}, journal = {Nihon Hoshasen Gijutsu Gakkai zasshi}, volume = {73}, number = {1}, pages = {33-41}, doi = {10.6009/jjrt.2017_JSRT_73.1.33}, pmid = {28111396}, issn = {0369-4305}, mesh = {Abdomen/*diagnostic imaging ; Adolescent ; Body Size ; Child ; Child, Preschool ; Humans ; Infant ; Infant, Newborn ; Radiation Dosage ; Radiographic Image Interpretation, Computer-Assisted ; Tomography, X-Ray Computed/instrumentation/*methods ; }, abstract = {We aimed to apply the pediatric abdominal CT protocol of Donnelly et al. in the United States to the pediatric abdominal CT-AEC. Examining CT images of 100 children, we found that the sectional area of the hepatic portal region (y) was strongly correlated with the body weight (x) as follows: y=7.14x + 84.39 (correlation coefficient=0.9574). We scanned an elliptical cone phantom that simulates the human body using a pediatric abdominal CT scanning method of Donnelly et al. in, and measured SD values. We further scanned the same phantom under the settings for adult CT-AEC scan and obtained the relationship between the sectional areas (y) and the SD values. Using these results, we obtained the following preset noise factors for CT-AEC at each body weight range: 6.90 at 4.5-8.9 kg, 8.40 at 9.0-17.9 kg, 8.68 at 18.0-26.9 kg, 9.89 at 27.0-35.9 kg, 12.22 at 36.0-45.0 kg, 13.52 at 45.1-70.0 kg, 15.29 at more than 70 kg. From the relation between age, weight and the distance of liver and tuber ischiadicum of 500 children, we obtained the CTDIvol values and DLP values under the scanning protocol of Donnelly et al. Almost all of DRL from these values turned out to be smaller than the DRL data of IAEA and various countries. Thus, by setting the maximum current values of CT-AEC to be the Donnelly et al.'s age-wise current values, and using our weight-wise noise factors, we think we can perform pediatric abdominal CT-AEC scans that are consistent with the same radiation safety and the image quality as those proposed by Donnelly et al.}, } @article {pmid28088875, year = {2017}, author = {Stein, DG and Sayeed, I and Espinosa-Garcia, C and Atif, F and Sergeeva, EG}, title = {Goldstein et al.'s Secondary Analysis of Progesterone Clinical Trial for Traumatic Brain Injury Can Only Reflect the Same Trial Design Flaws: A Response to "Very Early Administration of Progesterone Does Not Improve Neuropsychological Outcomes in Subjects with Moderate to Severe Traumatic Brain Injury".}, journal = {Journal of neurotrauma}, volume = {34}, number = {13}, pages = {2192-2193}, doi = {10.1089/neu.2016.4949}, pmid = {28088875}, issn = {1557-9042}, mesh = {*Brain Injuries, Traumatic ; Humans ; *Progesterone ; }, } @article {pmid28080155, year = {2018}, author = {Ghembaza, MEA and Lounici, A}, title = {Safety of Interferon Alpha-2a in Patients with Severe Ophthalmic Behçet's Disease: Response to Bielefeld et al.'s Letter.}, journal = {Ocular immunology and inflammation}, volume = {26}, number = {5}, pages = {793-794}, doi = {10.1080/09273948.2016.1265656}, pmid = {28080155}, issn = {1744-5078}, mesh = {Behcet Syndrome/*drug therapy ; Eye Diseases/*drug therapy ; Humans ; Interferon alpha-2 ; Interferon-alpha/*therapeutic use ; Recombinant Proteins/therapeutic use ; Treatment Outcome ; }, abstract = {Thyroid dysfunction is a common and severe side-effect encountered in up to 40% of patients treated with IFN-alpha-2a. The main two mechanisms by which IFN-alpha-2a induces thyroid dysfunction can be categorized as autoimmune and non-autoimmune disease. In the first subgroup, thyroid antibodies are found before treatment initiation, and then patients develop thyroiditis. In the second subgroup, IFN-alpha-2a induces thyroiditis by a direct cytotoxic effect on the thyroid gland; in this case, thyroid antibodies are usually negative. To avoid such complications, patients should undergo routine thyroid screening (thyroid-stimulating hormone and thyroid antibodies) prior to IFN-alpha-2a initiation, during the treatment period, and 6 months after treatment withdrawal.}, } @article {pmid28057011, year = {2017}, author = {Rosario, MS and Hayashi, K and Yamamoto, N and Takeuchi, A and Miwa, S and Taniguchi, Y and Tsuchiya, H}, title = {Functional and radiological outcomes of a minimally invasive surgical approach to monostotic fibrous dysplasia.}, journal = {World journal of surgical oncology}, volume = {15}, number = {1}, pages = {1}, pmid = {28057011}, issn = {1477-7819}, mesh = {Adolescent ; Adult ; Aged ; Bone Transplantation ; Child ; Female ; Fibrous Dysplasia, Monostotic/diagnostic imaging/pathology/*surgery ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Minimally Invasive Surgical Procedures/*methods ; Prognosis ; Radiography ; Retrospective Studies ; Young Adult ; }, abstract = {BACKGROUND: Reports showing high recurrence rates for intralesional curettage and bone grafting have made the current treatment principle for fibrous dysplasia controversial. This study aimed to report the postoperative clinical outcomes from three minimally invasive surgical strategies we use for monostotic fibrous dysplasia (MFD).

PATIENTS AND METHODS: Twelve patients with MFD presenting with no pathologic fracture or deformity and treated with one of three surgical strategies-plain open biopsy, plain alpha-tricalcium phosphate (ATP) reconstruction, and prophylactic bridge plating-were included. There were nine men and three women, with median age of 38 years. Mean follow-up was 88 weeks. Five cases involved the proximal femur, two each involved the femoral and tibial diaphyses, and one each involved the distal humerus, radial diaphysis, and proximal tibia. All cases were reviewed for functional and radiological outcomes.

RESULTS: Median time to full activity was 1 day (range 1 to 3) for the plain open biopsy group, while the prophylactic bridge-plating and plain ATP reconstruction groups had longer median recovery times (59 days, range 3 to 143, and 52 days, range 11 to 192, respectively). Musculoskeletal Tumor Society scores at last follow-up were excellent for all the cases (mean 29.6, range 25 to 30). Radiological analysis using Gaski et al.'s criteria showed plain open biopsy resulted in partial resolution of proximal femoral lesions, while ATP reconstruction and prophylactic plating resulted in no change and progression in this lesion site, respectively. For femoral diaphyseal lesions, prophylactic plating resulted in partial resolution, while ATP reconstruction resulted in no change. In the tibial diaphysis, prophylactic plating resulted in partial resolution, while plain open biopsy resulted in no change. For the lesions involving the distal humerus and the proximal tibia, plain open biopsy resulted in partial resolution, while for the radial diaphyseal lesion, ATP reconstruction resulted in no change. Radiological progression was limited in 11 (92%) cases, and none had postoperative complications.

CONCLUSION: Plain open biopsies for asymptomatic lesions; prophylactic bridge plating for symptomatic, large diaphyseal lytic lesions; and plain ATP reconstructions for both small and large nondiaphyseal symptomatic lytic lesions may be acceptable alternatives to curettage-incorporating procedures for MFD.}, } @article {pmid31162395, year = {2017}, author = {Kretzschmar, A}, title = {Sometimes Less Is Not Enough: A Commentary on Greiff et al. (2015).}, journal = {Journal of Intelligence}, volume = {5}, number = {1}, pages = {}, pmid = {31162395}, issn = {2079-3200}, abstract = {In this commentary, I discuss some critical issues in the study by Greiff, S.; Stadler, M.; Sonnleitner, P.; Wolff, C.; Martin, R., "Sometimes less is more: Comparing the validity of complex problem solving measures", Intelligence 2015, 50, 100-113. I conclude that-counter to the claims made in the original study-the specific study design was not suitable for deriving conclusions about the validity of different complex problem-solving (CPS) measurement approaches. Furthermore, a more elaborate consideration of previous CPS research was found to challenge Greiff et al.'s conclusions even further. Therefore, I argue that researchers should be aware of the differences between several kinds of CPS assessment tools and conceptualizations when the validity of CPS assessment tools is examined in future research.}, } @article {pmid28018268, year = {2016}, author = {Wiemers, M and Fischer, MH}, title = {Effects of Hand Proximity and Movement Direction in Spatial and Temporal Gap Discrimination.}, journal = {Frontiers in psychology}, volume = {7}, number = {}, pages = {1930}, pmid = {28018268}, issn = {1664-1078}, abstract = {Previous research on the interplay between static manual postures and visual attention revealed enhanced visual selection near the hands (near-hand effect). During active movements there is also superior visual performance when moving toward compared to away from the stimulus (direction effect). The "modulated visual pathways" hypothesis argues that differential involvement of magno- and parvocellular visual processing streams causes the near-hand effect. The key finding supporting this hypothesis is an increase in temporal and a reduction in spatial processing in near-hand space (Gozli et al., 2012). Since this hypothesis has, so far, only been tested with static hand postures, we provide a conceptual replication of Gozli et al.'s (2012) result with moving hands, thus also probing the generality of the direction effect. Participants performed temporal or spatial gap discriminations while their right hand was moving below the display. In contrast to Gozli et al. (2012), temporal gap discrimination was superior at intermediate and not near hand proximity. In spatial gap discrimination, a direction effect without hand proximity effect suggests that pragmatic attentional maps overshadowed temporal/spatial processing biases for far/near-hand space.}, } @article {pmid28004319, year = {2017}, author = {Alsayed, NS and Sereika, SM and Albrecht, SA and Terry, MA and Erlen, JA}, title = {Testing a model of health-related quality of life in women living with HIV infection.}, journal = {Quality of life research : an international journal of quality of life aspects of treatment, care and rehabilitation}, volume = {26}, number = {3}, pages = {655-663}, pmid = {28004319}, issn = {1573-2649}, mesh = {Antiretroviral Therapy, Highly Active ; Cross-Sectional Studies ; Depressive Disorder/psychology ; Female ; HIV Infections/drug therapy/*psychology ; Humans ; Middle Aged ; *Models, Theoretical ; Ohio ; *Patient Compliance ; Pennsylvania ; *Quality of Life ; Reproducibility of Results ; Women's Health ; }, abstract = {PURPOSE: The purpose of this secondary analysis was to test Ferrans et al.'s (J Nurs Scholarsh 37(4):336-342, 2005) revised model of health-related quality of life (HRQoL) (2005) modified from the Wilson and Cleary (J Am Med Assoc 273(1):59-65, 1995) model on women living with HIV. The primary aim was to test this model, examining the relations among the five central components (biological function, symptoms, functional status, general health perceptions, and HRQoL). The secondary aim was to explore the individual (age, children, race, marital status, education) and environmental (HIV-related stigma, social support) characteristics that may impact the main components of the model.

METHODS: This study employed a cross-sectional correlational design using baseline data from 178 women living with HIV/AIDS who participated in one of the two independent randomized controlled trials designed to enhance HIV medication adherence. Path analysis using structural equation modeling was used to examine the hypothesized multivariate relations proposed in the revised Wilson and Cleary (J Am Med Assoc 273(1):59-65, 1995) model of HRQoL.

RESULTS: While the revised model did not fit, exploratory post hoc modified models with a path from depressive symptoms to overall general health had an adequate model fit. Women with lower depressive symptoms (r = -.457, p < .01), lower HIV-related stigma (r = -.462, p < .01), higher social support (r = .413, p < .01), higher physical functioning (r = .350, p < .01), and higher general health perceptions (r = .537, p < .01) had higher overall HRQoL.

CONCLUSIONS: The results of this study have the potential to assist healthcare professionals in improving HRQoL for women living with HIV/AIDS.}, } @article {pmid28002981, year = {2017}, author = {Slotnick, SD}, title = {Resting-state fMRI data reflects default network activity rather than null data: A defense of commonly employed methods to correct for multiple comparisons.}, journal = {Cognitive neuroscience}, volume = {8}, number = {3}, pages = {141-143}, doi = {10.1080/17588928.2016.1273892}, pmid = {28002981}, issn = {1758-8936}, mesh = {Brain Mapping/*standards ; *Data Interpretation, Statistical ; Humans ; Image Processing, Computer-Assisted/*standards ; Magnetic Resonance Imaging/*standards ; }, abstract = {Analysis of functional magnetic resonance imaging (fMRI) data typically involves over one hundred thousand independent statistical tests; therefore, it is necessary to correct for multiple comparisons to control familywise error. In a recent paper, Eklund, Nichols, and Knutsson used resting-state fMRI data to evaluate commonly employed methods to correct for multiple comparisons and reported unacceptable rates of familywise error. Eklund et al.'s analysis was based on the assumption that resting-state fMRI data reflect null data; however, their 'null data' actually reflected default network activity that inflated familywise error. As such, Eklund et al.'s results provide no basis to question the validity of the thousands of published fMRI studies that have corrected for multiple comparisons or the commonly employed methods to correct for multiple comparisons.}, } @article {pmid28000142, year = {2017}, author = {Ebrahimpour, S and Mohammadi, M and Gholami, K}, title = {Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) with Teicoplanin: A Case Report.}, journal = {Drug safety - case reports}, volume = {4}, number = {1}, pages = {1}, pmid = {28000142}, issn = {2199-1162}, abstract = {Intramuscular teicoplanin (400 mg every 12 h for three doses, then 400 mg daily, intramuscularly) was prescribed for a 37-year-old woman with presumptive diagnosis of cellulitis. On the 14th day of treatment, she developed generalized maculopapular rash, accompanied by fever, wheezing, shortening of breath, and lymphadenopathy. Lab tests revealed abnormal liver enzymes, leukocytosis, and eosinophilia. The treatment was interrupted with suspicion of drug reaction. Fever subsided after 48 h. Skin eruption and respiratory symptoms began to resolve within 2 weeks. The follow-up lab tests performed 1 month later indicated resolution of liver dysfunction. With respect to delayed onset of symptoms including fever, generalized rash, lymphadenopathy, and organ involvement, drug reaction with eosinophilia and systemic symptoms (DRESS) was highly suspected. The causality was evaluated by conventional scoring systems. The reaction was rated as probable (score = 5) according to RegiSCAR and possible (score = 5) based on Kardaun et al.'s scoring system. However, DRESS was not confirmed by the Japanese group's criteria for diagnosis of DRESS/drug-induced hypersensitivity syndrome (DIHS).}, } @article {pmid27983874, year = {2017}, author = {Jansson, J and Rajaby, R}, title = {A More Practical Algorithm for the Rooted Triplet Distance.}, journal = {Journal of computational biology : a journal of computational molecular cell biology}, volume = {24}, number = {2}, pages = {106-126}, doi = {10.1089/cmb.2016.0185}, pmid = {27983874}, issn = {1557-8666}, mesh = {*Algorithms ; Computer Simulation ; *Models, Genetic ; *Phylogeny ; Software ; }, abstract = {The rooted triplet distance is a measure of the dissimilarity of two phylogenetic trees with identical leaf label sets. An algorithm by Brodal et al. that computes it in [Formula: see text] time and [Formula: see text] space, where n is the number of leaf labels, has recently been implemented in the software package tqDist. In this article, we show that replacing the hierarchical decomposition tree used in Brodal et al.'s algorithm by a centroid paths-based data structure yields an [Formula: see text]-time and [Formula: see text]-space algorithm that, although slower in theory, is faster in practice as well as less memory consuming. Simulations for values of n up to 4,000,000 support our claims experimentally.}, } @article {pmid27983616, year = {2016}, author = {Park, Y and Park, Y}, title = {Three-Factor User Authentication and Key Agreement Using Elliptic Curve Cryptosystem in Wireless Sensor Networks.}, journal = {Sensors (Basel, Switzerland)}, volume = {16}, number = {12}, pages = {}, pmid = {27983616}, issn = {1424-8220}, abstract = {Secure communication is a significant issue in wireless sensor networks. User authentication and key agreement are essential for providing a secure system, especially in user-oriented mobile services. It is also necessary to protect the identity of each individual in wireless environments to avoid personal privacy concerns. Many authentication and key agreement schemes utilize a smart card in addition to a password to support security functionalities. However, these schemes often fail to provide security along with privacy. In 2015, Chang et al. analyzed the security vulnerabilities of previous schemes and presented the two-factor authentication scheme that provided user privacy by using dynamic identities. However, when we cryptanalyzed Chang et al.'s scheme, we found that it does not provide sufficient security for wireless sensor networks and fails to provide accurate password updates. This paper proposes a security-enhanced authentication and key agreement scheme to overcome these security weaknesses using biometric information and an elliptic curve cryptosystem. We analyze the security of the proposed scheme against various attacks and check its viability in the mobile environment.}, } @article {pmid27982481, year = {2017}, author = {Stork, NE and Srivastava, DS and Eggleton, P and Hodda, M and Lawson, G and Leakey, RRB and Watt, AD}, title = {Consistency of effects of tropical-forest disturbance on species composition and richness relative to use of indicator taxa.}, journal = {Conservation biology : the journal of the Society for Conservation Biology}, volume = {31}, number = {4}, pages = {924-933}, doi = {10.1111/cobi.12883}, pmid = {27982481}, issn = {1523-1739}, mesh = {Animals ; *Biodiversity ; Cameroon ; *Conservation of Natural Resources ; *Forests ; Trees ; }, abstract = {Lawton et al. (1998) found, in a highly cited study, that the species richness of 8 taxa each responds differently to anthropogenic disturbance in Cameroon forests. Recent developments in conservation science suggest that net number of species is an insensitive measure of change and that understanding which species are affected by disturbance is more important. It is also recognized that all disturbance types are not equal in their effect on species and that grouping species according to function rather than taxonomy is more informative of responses of biodiversity to change. In a reanalysis of most of the original Cameroon data set (canopy and ground ants, termites, canopy beetles, nematodes, and butterflies), we focused on changes in species and functional composition rather than richness and used a more inclusive measure of forest disturbance based on 4 component drivers of change: years since disturbance, tree cover, soil compaction, and degree of tree removal. Effects of disturbance on compositional change were largely concordant between taxa. Contrary to Lawton et al.'s findings, species richness for most groups did not decline with disturbance level, providing support for the view that trends in species richness at local scales do not reflect the resilience of ecosystems to disturbance. Disturbance affected species composition more strongly than species richness for butterflies, canopy beetles, and litter ants. For these groups, disturbance caused species replacements rather than just species loss. Only termites showed effects of disturbance on species richness but not composition, indicating species loss without replacement. Although disturbance generally caused changes in composition, the strength of this relationship depended on the disturbance driver. Butterflies, litter ants, and nematodes were correlated with amount of tree cover, canopy beetles were most strongly correlated with time since disturbance, and termites were most strongly correlated with degree of soil disturbance. There were moderately divergent responses to disturbance between functional feeding groups. Disturbance was most strongly correlated with compositional differences of herbivores within beetles and nematodes and humus feeders within termites. Our results suggest that consideration of the impact of different forms of disturbance on species and functional composition, rather than on net numbers of species, is important when assessing the impacts of disturbance on biodiversity.}, } @article {pmid27982437, year = {2017}, author = {Fluegge, K}, title = {Commentary: 'Unhealthy diet,' nutrient status, and ADHD symptoms: a confounding role for environmental nitrous oxide exposure - reflections on Rijlaarsdam et al. (2016).}, journal = {Journal of child psychology and psychiatry, and allied disciplines}, volume = {58}, number = {1}, pages = {28-29}, doi = {10.1111/jcpp.12649}, pmid = {27982437}, issn = {1469-7610}, support = {MC_UU_12013/2/MRC_/Medical Research Council/United Kingdom ; MC_UU_12013/8/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Animals ; *Attention Deficit Disorder with Hyperactivity ; DNA Methylation ; Diet ; Environmental Exposure ; Humans ; *Nitrous Oxide ; Rats ; }, abstract = {Rijlaarsdam et al. (2016) recently published their findings utilizing a longitudinal design showing that prenatal 'unhealthy diet' was positively associated with IGF2 DNA methylation at birth across both youth cohorts. However, only in the EOP youth was prenatal 'unhealthy diet' positively associated with ADHD symptoms presumably through IGF2 DNA hypermethylation. Rijlaarsdam et al.'s () choice to assess high fat and sugar diet with the Food Frequency Questionnaire (FFQ) may offer some indication as to prenatal nutrient status, as the foods identified by the FFQ in their study are relatively low in free choline. It has been shown that gestational choline deficiency in rats leads to hypermethylation of IGF2. Consistent with the literature describing an association between air pollution and cognitive neurodevelopmental impairment, the author of this commentary has previously proposed through empirical investigation that chronic environmental exposure to the trace levels of the pervasive air pollutant, nitrous oxide (N2 O), may facilitate core features of neurodevelopmental disorders, like ADHD. Impaired acetylcholine synthesis in rats exposed to N2 O has been shown, with a 53% reduction in [1-2H2,2-2H2] choline. Low-dose N2 O exposure is also thought to stimulate central release of opioid peptides, like dynorphin, which play a role in significantly increasing food intake behavior and/or modulating sucrose intake. Taken altogether, these studies present a strong confounder to the interpretation made by Rijlaarsdam et al. () that prenatal 'unhealthy diet' may play a role in the onset of ADHD symptoms in youth with EOP conduct problems through induction of IGF2 DNA hypermethylation. While the 'unhealthy diet' may represent possible maternal nutrient deficiencies during gestation, it is also possible that exposure to air pollutants, particularly N2 O, may not only directly reduce fetal cholinergic status thereby enhancing IGF2 DNA hypermethylation but may also significantly modulate maternal food intake behaviors (i.e. sucrose).}, } @article {pmid27967105, year = {2016}, author = {Christov, IC and Jordan, PM}, title = {Comment on "Locomotion of a microorganism in weakly viscoelastic liquids".}, journal = {Physical review. E}, volume = {94}, number = {5-2}, pages = {057101}, doi = {10.1103/PhysRevE.94.057101}, pmid = {27967105}, issn = {2470-0053}, abstract = {We point out, and show the implications of resolving, an apparent conceptual difficulty in a recent article by De Corato et al. [Phys. Rev. E 92, 053008 (2015)PLEEE81539-375510.1103/PhysRevE.92.053008] on the locomotion of certain microorganisms in a second-grade fluid. The difficulty arises due to the assumption that α_{1} <0, where α_{1} is the first normal stress modulus of the (non-Newtonian) liquid, was chosen for this study. In particular, this choice of sign for α_{1} is inconsistent with thermodynamics, and as such casts considerable doubt on De Corato et al.'s assumption regarding the existence of a steady-state solution of the equations of motion of the fluid.}, } @article {pmid27965828, year = {2016}, author = {Mitchell, F and Jahoda, A and Hankey, C and Matthews, L and Murray, H and Melville, C}, title = {'Moving on and feeling good': a feasibility study to explore the lifestyle behaviours of young adults with intellectual disabilities as they transition from school to adulthood-a study protocol.}, journal = {Pilot and feasibility studies}, volume = {2}, number = {}, pages = {8}, pmid = {27965828}, issn = {2055-5784}, support = {MC_UU_12017/14/MRC_/Medical Research Council/United Kingdom ; SPHSU14/CSO_/Chief Scientist Office/United Kingdom ; }, abstract = {BACKGROUND: The transition from adolescence to adulthood is a 'high-risk' period for weight gain in the general population. There is speculation that this may also be a risk period for adults with intellectual disabilities; however, there has been no research which has monitored change in health indicators. Since adults with intellectual disabilities have higher rates of obesity and engage in more sedentary behaviour and less physical activity than the general population, there is a need to understand more about the lifestyle behaviours of this population during the transition to adulthood. This protocol paper will provide details of the moving on and feeling good feasibility study, designed for young people with intellectual disabilities.

METHODS/DESIGN: A multi-point recruitment strategy will be used to recruit 30 participants with a mild-moderate level of intellectual disability. The aim of the feasibility study is to examine the feasibility of recruitment, participant retention and the measurement of relevant health behaviour outcomes. The study will assess the feasibility of monitoring weight, diet and physical activity levels in adolescents over a 12-month transitional period from school to adult life. This mixed method study will provide insight into the lives of young people with intellectual disabilities and will examine the use of Walker et al.'s social-ecological approach to promote self-determination specific to lifestyle behaviours, during this transition period. Baseline data will be collected during the final year of school, with follow-up data collection at 6 and 12 months. Anthropometric (weight, height, waist and hip circumference), objective physical activity measures (7-day accelerometer wear) and dietary and choice measures will be collected at each time point to assess the feasibility of measuring diet patterns, food frequency, physical activity and BMI. Furthermore, ten participants will be selected for short semi-structured scoping interviews at baseline and 12-month follow-up, to gain information on psychological, social and environmental factors which might affect behaviour change.

DISCUSSION: The outcomes from the feasibility study will aid the development and piloting of a sufficiently powered randomised controlled trial. This would allow us to evaluate the effectiveness and sustainability of a lifestyle behaviour intervention, over a 5-year transition period.}, } @article {pmid27943596, year = {2017}, author = {Bateson, M and Nettle, D}, title = {The telomere lengthening conundrum - it could be biology.}, journal = {Aging cell}, volume = {16}, number = {2}, pages = {312-319}, pmid = {27943596}, issn = {1474-9726}, support = {666669/ERC_/European Research Council/International ; NC/K000802/1/NC3RS_/National Centre for the Replacement, Refinement and Reduction of Animals in Research/United Kingdom ; }, mesh = {Computer Simulation ; Models, Biological ; *Telomere Homeostasis ; }, abstract = {Longitudinal studies of human leucocyte telomere length often report a percentage of individuals whose telomeres appear to lengthen. However, based on theoretical considerations and empirical data, Steenstrup et al. (Nucleic Acids Research, 2013, vol 41(13): e131) concluded that this lengthening is unlikely to be a real biological phenomenon and is more likely to be an artefact of measurement error. We dispute the logic underlying this claim. We argue that Steenstrup et al.'s analysis is incomplete because it failed to compare predictions derived from assuming a scenario with no true telomere lengthening with alternative scenarios in which true lengthening occurs. To address this deficit, we built a computational model of telomere dynamics that allowed us to compare the predicted percentage of observed telomere length gainers given differing assumptions about measurement error and the true underling dynamics. We modelled a set of scenarios, all assuming measurement error, but both with and without true telomere lengthening. We found a range of scenarios assuming some true telomere lengthening that yielded either similar or better quantitative fits to the empirical data on the percentage of individuals showing apparent telomere lengthening. We conclude that although measurement error contributes to the prevalence of apparent telomere lengthening, Steenstrup et al.'s conclusion was too strong, and current data do not allow us to reject the hypothesis that true telomere lengthening is a real biological phenomenon in epidemiological studies. Our analyses highlight the need for process-level models in the analysis of telomere dynamics.}, } @article {pmid27929302, year = {2017}, author = {Twenge, JM and Carter, NT and Campbell, WK}, title = {Age, time period, and birth cohort differences in self-esteem: Reexamining a cohort-sequential longitudinal study.}, journal = {Journal of personality and social psychology}, volume = {112}, number = {5}, pages = {e9-e17}, doi = {10.1037/pspp0000122}, pmid = {27929302}, issn = {1939-1315}, mesh = {Adult ; Age Factors ; Aged ; Aged, 80 and over ; Cohort Studies ; Female ; Humans ; Longitudinal Studies ; Male ; Middle Aged ; *Self Concept ; Time ; }, abstract = {Orth, Trzesniewski, and Robins (2010) concluded that the nationally representative Americans' Changing Lives (ACL) cohort-sequential study demonstrated moderate to large age differences in self-esteem, and no birth cohort (generational) differences in the age trajectory. In a reanalysis of these data using 2 different statistical techniques, we find significant increases in self-esteem that could be attributed to birth cohort or time period. First, hierarchical linear modeling analyses with birth cohort as a continuous variable (vs. the multiple group formulation used by Orth et al.) find that birth cohort has a measurable influence on self-esteem through its interaction with age. Participants born in later years (e.g., 1960) were higher in self-esteem and were more likely to increase in self-esteem as they aged than participants born in earlier years (e.g., 1920). However, the estimated age trajectory up to age 60 is similar in Orth et al.'s results and in the results from our analyses including cohort. Second, comparing ACL respondents of the same age in 1986 versus 2002 (a time-lag design) yields significant birth cohort differences in self-esteem, with 2002 participants of the same age higher in self-esteem than those in 1986. Combined with some previous studies finding significant increases in self-esteem and positive self-views over time, these results suggest that cultural change in the form of cohort and time period cannot be ignored as influences in cross-sectional and longitudinal studies. (PsycINFO Database Record}, } @article {pmid27908603, year = {2017}, author = {Sterckx, S and Cockbain, J and Pennings, G}, title = {Patenting medical diagnosis methods in Europe: Stanford University and time-lapse microscopy.}, journal = {Reproductive biomedicine online}, volume = {34}, number = {2}, pages = {166-168}, doi = {10.1016/j.rbmo.2016.10.014}, pmid = {27908603}, issn = {1472-6491}, mesh = {California ; Embryo, Mammalian/*diagnostic imaging ; Europe ; *Fertilization in Vitro ; Humans ; Microscopy/*methods ; Patents as Topic/*legislation & jurisprudence ; Time-Lapse Imaging/*methods ; Universities ; }, abstract = {In 2013, a European Patent for the technique of time-lapse microscopy was granted by the European Patent Office (EPO) to Stanford University and was subsequently opposed by Unisense FertiliTech A/S and by the European Society for Human Reproduction and Embryology (ESHRE), Sigrid Sterckx, Julian Cockbain and Guido Pennings. ESHRE et al.'s opposition was based on the argument that Stanford's patent was directed to a method of medical diagnosis, methods that are excluded from patentability by Article 53(c) of the European Patent Convention. The Opposition Division of the EPO rejected the oppositions in November 2015, and both opponents have now filed their appeals. In this paper, we comment on the Opposition Division decision and the grounds of appeal put forward by ESHRE et al.}, } @article {pmid27899479, year = {2017}, author = {Such, E and Salway, S and Copeland, R and Haake, S and Domone, S and Mann, S}, title = {A formative review of physical activity interventions for minority ethnic populations in England.}, journal = {Journal of public health (Oxford, England)}, volume = {39}, number = {4}, pages = {e265-e274}, pmid = {27899479}, issn = {1741-3850}, mesh = {*Ethnicity ; Exercise ; *Exercise Therapy ; Health Promotion ; Humans ; *Minority Groups ; United Kingdom ; }, abstract = {BACKGROUND: Physical activity (PA) levels are lower among some UK Black and minority ethnic (BME) groups than the majority White British population and a variety of tailored interventions have emerged. This study documents the characteristics and logic of local adaptations, a vital first step in evaluating such innovations.

METHODS: An English PA data set was examined to identify and characterize PA programmes focussed on BME populations. Three case studies were conducted, employing documentary analysis and qualitative interviews. Netto et al.'s principles of adapting health promotion interventions for BME populations guided the analysis.

RESULTS: Out of 861 PA interventions, 57 focussed on BME populations. These were typically aimed to engage the most inactive groups, improve both health and social outcomes and were largely publically/charitably funded. Tailored approaches matched Netto et al.'s five principles: using community resources for publicity, identifying and addressing barriers, developing sensitive communication strategies, working with values and accommodating cultural identification. Another common principle was identified: building community capacity for sustainability.

CONCLUSIONS: PA interventions tailored to the needs of BME groups reflect their largely disadvantaged position in society and focus on inactivity. The six principles could be used as a framework for developing, designing and evaluating tailored interventions for BME populations.}, } @article {pmid27896983, year = {2017}, author = {Stanescu, A and Pandey, G}, title = {LEARNING PARSIMONIOUS ENSEMBLES FOR UNBALANCED COMPUTATIONAL GENOMICS PROBLEMS.}, journal = {Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing}, volume = {22}, number = {}, pages = {288-299}, pmid = {27896983}, issn = {2335-6936}, support = {R01 GM114434/GM/NIGMS NIH HHS/United States ; }, mesh = {*Algorithms ; Arabidopsis/genetics ; Computational Biology/*methods/statistics & numerical data ; Databases, Genetic/statistics & numerical data ; Genomics/*methods/statistics & numerical data ; Machine Learning ; Proteins/chemistry/genetics/metabolism ; RNA Splice Sites ; }, abstract = {Prediction problems in biomedical sciences are generally quite difficult, partially due to incomplete knowledge of how the phenomenon of interest is influenced by the variables and measurements used for prediction, as well as a lack of consensus regarding the ideal predictor(s) for specific problems. In these situations, a powerful approach to improving prediction performance is to construct ensembles that combine the outputs of many individual base predictors, which have been successful for many biomedical prediction tasks. Moreover, selecting a parsimonious ensemble can be of even greater value for biomedical sciences, where it is not only important to learn an accurate predictor, but also to interpret what novel knowledge it can provide about the target problem. Ensemble selection is a promising approach for this task because of its ability to select a collectively predictive subset, often a relatively small one, of all input base predictors. One of the most well-known algorithms for ensemble selection, CES (Caruana et al.'s Ensemble Selection), generally performs well in practice, but faces several challenges due to the difficulty of choosing the right values of its various parameters. Since the choices made for these parameters are usually ad-hoc, good performance of CES is difficult to guarantee for a variety of problems or datasets. To address these challenges with CES and other such algorithms, we propose a novel heterogeneous ensemble selection approach based on the paradigm of reinforcement learning (RL), which offers a more systematic and mathematically sound methodology for exploring the many possible combinations of base predictors that can be selected into an ensemble. We develop three RL-based strategies for constructing ensembles and analyze their results on two unbalanced computational genomics problems, namely the prediction of protein function and splice sites in eukaryotic genomes. We show that the resultant ensembles are indeed substantially more parsimonious as compared to the full set of base predictors, yet still offer almost the same classification power, especially for larger datasets. The RL ensembles also yield a better combination of parsimony and predictive performance as compared to CES.}, } @article {pmid27889281, year = {2017}, author = {Regnerus, M}, title = {Is structural stigma's effect on the mortality of sexual minorities robust? A failure to replicate the results of a published study.}, journal = {Social science & medicine (1982)}, volume = {188}, number = {}, pages = {157-165}, doi = {10.1016/j.socscimed.2016.11.018}, pmid = {27889281}, issn = {1873-5347}, mesh = {Adult ; Female ; Humans ; Male ; Middle Aged ; *Mortality ; Research Design/*standards ; Risk Factors ; *Sexual and Gender Minorities ; Social Determinants of Health/*trends ; Social Discrimination ; *Social Stigma ; }, abstract = {BACKGROUND: The study of stigma's influence on health has surged in recent years. Hatzenbuehler et al.'s (2014) study of structural stigma's effect on mortality revealed an average of 12 years' shorter life expectancy for sexual minorities who resided in communities thought to exhibit high levels of anti-gay prejudice, using data from the 1988-2002 administrations of the US General Social Survey linked to mortality outcome data in the 2008 National Death Index.

METHODS: In the original study, the key predictor variable (structural stigma) led to results suggesting the profound negative influence of structural stigma on the mortality of sexual minorities. Attempts to replicate the study, in order to explore alternative hypotheses, repeatedly failed to generate the original study's key finding on structural stigma. Efforts to discern the source of the disparity in results revealed complications in the multiple imputation process for missing values of the components of structural stigma. This prompted efforts at replication using 10 different imputation approaches.

RESULTS: Efforts to replicate Hatzenbuehler et al.'s (2014) key finding on structural stigma's notable influence on the premature mortality of sexual minorities, including a more refined imputation strategy than described in the original study, failed. No data imputation approach yielded parameters that supported the original study's conclusions. Alternative hypotheses, which originally motivated the present study, revealed little new information.

CONCLUSION: Ten different approaches to multiple imputation of missing data yielded none in which the effect of structural stigma on the mortality of sexual minorities was statistically significant. Minimally, the original study's structural stigma variable (and hence its key result) is so sensitive to subjective measurement decisions as to be rendered unreliable.}, } @article {pmid27885547, year = {2017}, author = {Foley-Nicpon, M and L Fosenburg, S and G Wurster, K and Assouline, SG}, title = {Identifying High Ability Children with DSM-5 Autism Spectrum or Social Communication Disorder: Performance on Autism Diagnostic Instruments.}, journal = {Journal of autism and developmental disorders}, volume = {47}, number = {2}, pages = {460-471}, pmid = {27885547}, issn = {1573-3432}, mesh = {Adolescent ; Algorithms ; Autistic Disorder/*diagnosis/*psychology ; Child ; Child, Preschool ; Developmental Disabilities/diagnosis/psychology ; *Diagnostic and Statistical Manual of Mental Disorders ; Female ; Humans ; Male ; Social Communication Disorder/*diagnosis/*psychology ; }, abstract = {This study was a replication of Mazefsky et al.'s (Journal of Autism and Developmental Disabilities 43:1236-1242, 2013) investigation among a sample of 45 high ability children and adolescents diagnosed with ASD under DSM-IV-TR. Items from the ADOS and ADI-R were mapped onto DSM-5 diagnostic criteria for ASD and SCD to determine whether participants would meet either diagnosis under DSM-5. If the ADOS were administered alone, 62% of individuals diagnosed with ASD would no longer meet criteria under DSM-5; however, when the ADI-R and ADOS scores were combined, 100% of individuals would continue to meet ASD diagnosis. The ADOS was determined to be an insufficient measure for SCD due to the small number of algorithm items measuring SCD diagnostic criteria, suggesting the development of SCD measures is required.}, } @article {pmid27882504, year = {2017}, author = {Racine, E and Nguyen, V and Saigle, V and Dubljevic, V}, title = {Media Portrayal of a Landmark Neuroscience Experiment on Free Will.}, journal = {Science and engineering ethics}, volume = {23}, number = {4}, pages = {989-1007}, pmid = {27882504}, issn = {1471-5546}, mesh = {Ethics, Research ; Humans ; Mass Media/*standards ; Neurosciences/*ethics/standards/trends ; *Personal Autonomy ; }, abstract = {The concept of free will has been heavily debated in philosophy and the social sciences. Its alleged importance lies in its association with phenomena fundamental to our understandings of self, such as autonomy, freedom, self-control, agency, and moral responsibility. Consequently, when neuroscience research is interpreted as challenging or even invalidating this concept, a number of heated social and ethical debates surface. We undertook a content analysis of media coverage of Libet's et al.'s (Brain 106(Pt 3):623-642, 1983) landmark study, which is frequently interpreted as posing a serious challenge to the existence of free will. Media descriptions of Libet et al.'s experiment provided limited details about the original study. Overall, many media articles reported that Libet et al.'s experiments undermined the existence of free will, despite acknowledging that several methodological limitations had been identified in the literature. A propensity to attribute greater credibility than warranted to neurobiological explanations could be at stake.}, } @article {pmid27877119, year = {2016}, author = {Clancy, F and Prestwich, A and Caperon, L and O'Connor, DB}, title = {Perseverative Cognition and Health Behaviors: A Systematic Review and Meta-Analysis.}, journal = {Frontiers in human neuroscience}, volume = {10}, number = {}, pages = {534}, pmid = {27877119}, issn = {1662-5161}, abstract = {Recent developments in stress theory have emphasized the significance of perseverative cognition (worry and rumination) in furthering our understanding of stress-disease relationships. Substantial evidence has shown that perseverative cognition (PC) is associated with somatic outcomes and numerous physiological concomitants have been identified (i.e., cardiovascular, autonomic, and endocrine nervous system activity parameters). However, there has been no synthesis of the evidence regarding the association between PC and health behaviors. This is important given such behaviors may also directly and/or indirectly influence health and disease outcomes (triggered by PC). Therefore, the aim of the current review was to synthesize available studies that have explored the relationship between worry and rumination and health behaviors (health risk: behaviors which, if performed, would be detrimental to health; health promoting: behaviors which, if performed, would be beneficial for health). A systematic review and meta-analyses of the literature were conducted. Studies were included in the review if they reported the association between PC and health behavior. Studies identified in MEDLINE or PsycINFO (k = 7504) were screened, of which 19 studies met the eligibility criteria. Random-effects meta-analyses suggested increased PC was generally associated with increased health risk behaviors but not health promoting behaviors. Further analyses indicated that increases in rumination (r = 0.122), but not reflection (r = -0.080), or worry (r = 0.048) were associated with health risk behaviors. In conclusion, these results showed that increases in PC are associated with increases in health risk behaviors (substance use, alcohol consumption, unhealthy eating, and smoking) that are driven primarily through rumination. These findings provide partial support for our hypothesis that in Brosschot et al.'s (2006) original perseverative cognition hypothesis, there may be scope for additional routes to pathogenic disease via poorer health behaviors.}, } @article {pmid27875155, year = {2017}, author = {Beecham, R and Dykes, J and Meulemans, W and Slingsby, A and Turkay, C and Wood, J}, title = {Map LineUps: Effects of spatial structure on graphical inference.}, journal = {IEEE transactions on visualization and computer graphics}, volume = {23}, number = {1}, pages = {391-400}, doi = {10.1109/TVCG.2016.2598862}, pmid = {27875155}, issn = {1941-0506}, abstract = {Fundamental to the effective use of visualization as an analytic and descriptive tool is the assurance that presenting data visually provides the capability of making inferences from what we see. This paper explores two related approaches to quantifying the confidence we may have in making visual inferences from mapped geospatial data. We adapt Wickham et al.'s 'Visual Line-up' method as a direct analogy with Null Hypothesis Significance Testing (NHST) and propose a new approach for generating more credible spatial null hypotheses. Rather than using as a spatial null hypothesis the unrealistic assumption of complete spatial randomness, we propose spatially autocorrelated simulations as alternative nulls. We conduct a set of crowdsourced experiments (n=361) to determine the just noticeable difference (JND) between pairs of choropleth maps of geographic units controlling for spatial autocorrelation (Moran's I statistic) and geometric configuration (variance in spatial unit area). Results indicate that people's abilities to perceive differences in spatial autocorrelation vary with baseline autocorrelation structure and the geometric configuration of geographic units. These results allow us, for the first time, to construct a visual equivalent of statistical power for geospatial data. Our JND results add to those provided in recent years by Klippel et al. (2011), Harrison et al. (2014) and Kay & Heer (2015) for correlation visualization. Importantly, they provide an empirical basis for an improved construction of visual line-ups for maps and the development of theory to inform geospatial tests of graphical inference.}, } @article {pmid27870086, year = {2016}, author = {Duvernay-Tardif, L}, title = {Health Care for NFL Players: Upholding Physician Standards and Enhancing the Doctor-Patient Relationship.}, journal = {The Hastings Center report}, volume = {46 Suppl 2}, number = {}, pages = {S31-S32}, doi = {10.1002/hast.654}, pmid = {27870086}, issn = {1552-146X}, mesh = {Conflict of Interest ; Football/*injuries ; Humans ; Male ; *Physician's Role ; Physician-Patient Relations/*ethics ; Physicians/*ethics/*standards ; Professional Practice/ethics ; Return to Sport/ethics ; Sports Medicine/*standards ; *Trust ; United States ; }, abstract = {Beginning my third year with the Kansas City Chiefs and being also a medical student at McGill University, I was at first a little reluctant to comment on Glenn Cohen et al.'s critique of the National Football League's structure involving player health and team doctors, but the opportunity to provide a perspective as both a football player and a medical student was too much to forgo. Because of my athletic and academic background, I am often asked what I think about injuries in professional sports and about the role of sports medicine physicians, and Cohen et al.'s article demands a thoughtful reaction. I want to suggest that the fundamental principles concerning the medical profession and the doctor-patient relationship provide additional arguments for some of the solutions that Cohen et al. discuss. The professional self-regulation that the proposed medical committee could provide and the reliance on a doctor who was not hired by the player's employer-the club-for a second opinion are both good ways to minimize conflicts of interest.}, } @article {pmid27866854, year = {2017}, author = {Crilley, LR and Lucarelli, F and Bloss, WJ and Harrison, RM and Beddows, DC and Calzolai, G and Nava, S and Valli, G and Bernardoni, V and Vecchi, R}, title = {Source apportionment of fine and coarse particles at a roadside and urban background site in London during the 2012 summer ClearfLo campaign.}, journal = {Environmental pollution (Barking, Essex : 1987)}, volume = {220}, number = {Pt B}, pages = {766-778}, doi = {10.1016/j.envpol.2016.06.002}, pmid = {27866854}, issn = {1873-6424}, mesh = {Air Pollutants/*analysis ; Air Pollution/*analysis ; *Cities ; Environmental Monitoring ; London ; Particle Size ; Particulate Matter/*analysis ; *Rural Population ; Seasons ; Trace Elements/*analysis ; Vehicle Emissions/analysis ; }, abstract = {London, like many major cities, has a noted air pollution problem, and a better understanding of the sources of airborne particles in the different size fractions will facilitate the implementation and effectiveness of control strategies to reduce air pollution. Thus, the trace elemental composition of the fine and coarse fraction were analysed at hourly time resolution at urban background (North Kensington, NK) and roadside (Marylebone Road, MR) sites within central London. Unlike previous work, the current study focuses on measurements during the summer providing a snapshot of contributing sources, utilising the high time resolution to improve source identification. Roadside enrichment was observed for a large number of elements associated with traffic emissions (Al, S, Ca, Ti, V, Cr, Mn, Fe, Ni, Cu, Zn, As, Rb and Zr), while those elements that are typically from more regional sources (e.g. Na, Cl, S and K) were not found to have an appreciable increment. Positive Matrix Factorization (PMF) was applied for the source apportionment of the particle mass at both sites with similar sources being identified, including sea salt, airborne soil, traffic emissions, secondary inorganic aerosols and a Zn-Pb source. In the fine fraction, traffic emissions was the largest contributing source at MR (31.9%), whereas it was incorporated within an "urban background" source at NK, which had contributions from wood smoke, vehicle emissions and secondary particles. Regional sources were the major contributors to the coarse fraction at both sites. Secondary inorganic aerosols (which contained influences from shipping emissions and coal combustion) source factors accounted for around 33% of the PM10 at NK and were found to have the highest contributions from regional sources, including from the European mainland. Exhaust and non-exhaust sources both contribute appreciably to PM10 levels at the MR site, highlighting the continuing importance of vehicle-related air pollutants at roadside.}, } @article {pmid27866722, year = {2017}, author = {Carvalho-Oliveira, R and Amato-Lourenço, LF and Moreira, TC and Silva, DR and Vieira, BD and Mauad, T and Saiki, M and Saldiva, PH}, title = {Effectiveness of traffic-related elements in tree bark and pollen abortion rates for assessing air pollution exposure on respiratory mortality rates.}, journal = {Environment international}, volume = {99}, number = {}, pages = {161-169}, doi = {10.1016/j.envint.2016.09.008}, pmid = {27866722}, issn = {1873-6750}, mesh = {Aged ; Aged, 80 and over ; Air Pollutants/*analysis ; Brazil/epidemiology ; Environmental Monitoring/*methods ; Humans ; Lung Neoplasms/chemically induced/*mortality ; Middle Aged ; Plant Bark/*chemistry ; Pollen/*chemistry ; Pulmonary Disease, Chronic Obstructive/chemically induced/*mortality ; Vehicle Emissions/*analysis ; }, abstract = {The majority of epidemiological studies correlate the cardiorespiratory effects of air pollution exposure by considering the concentrations of pollutants measured from conventional monitoring networks. The conventional air quality monitoring methods are expensive, and their data are insufficient for providing good spatial resolution. We hypothesized that bioassays using plants could effectively determine pollutant gradients, thus helping to assess the risks associated with air pollution exposure. The study regions were determined from different prevalent respiratory death distributions in the Sao Paulo municipality. Samples of tree flower buds were collected from twelve sites in four regional districts. The genotoxic effects caused by air pollution were tested through a pollen abortion bioassay. Elements derived from vehicular traffic that accumulated in tree barks were determined using energy-dispersive X-ray fluorescence spectrometry (EDXRF). Mortality data were collected from the mortality information program of Sao Paulo City. Principal component analysis (PCA) was applied to the concentrations of elements accumulated in tree barks. Pearson correlation and exponential regression were performed considering the elements, pollen abortion rates and mortality data. PCA identified five factors, of which four represented elements related to vehicular traffic. The elements Al, S, Fe, Mn, Cu, and Zn showed a strong correlation with mortality rates (R[2]>0.87) and pollen abortion rates (R[2]>0.82). These results demonstrate that tree barks and pollen abortion rates allow for correlations between vehicular traffic emissions and associated outcomes such as genotoxic effects and mortality data.}, } @article {pmid27865439, year = {2017}, author = {Rabenold, D}, title = {A scratch by any other name: A comment on Lucas et al.'s reply to "Scratching the surface: A critique of Lucas et al. (2013)'s conclusion that phytoliths do not abrade enamel" [J. Hum. Evol. 74 (2016) 130-133].}, journal = {Journal of human evolution}, volume = {102}, number = {}, pages = {78-80}, doi = {10.1016/j.jhevol.2016.09.006}, pmid = {27865439}, issn = {1095-8606}, mesh = {*Dental Enamel ; *Paleodontology ; }, } @article {pmid27863327, year = {2017}, author = {Setoh, P and Marschik, PB and Einspieler, C and Esposito, G}, title = {Autism spectrum disorder and early motor abnormalities: Connected or coincidental companions?.}, journal = {Research in developmental disabilities}, volume = {60}, number = {}, pages = {13-15}, doi = {10.1016/j.ridd.2016.11.001}, pmid = {27863327}, issn = {1873-3379}, mesh = {Humans ; *Autism Spectrum Disorder ; Autistic Disorder/epidemiology ; *Friends ; Parents ; }, abstract = {Research in the past decade has produced a growing body of evidence showing that motor abnormalities in individuals with autism spectrum disorder (ASD) are the rule rather than the exception. The paper by Chinello and colleagues furthers our understanding of the importance of studying motor functions in ASD by testing a non-clinical population of parents-infant triads. Chinello and colleagues' findings seem to suggest that subclinical motor impairments may exist in the typical population with inherited non-clinical ASD traits. Chinello and colleagues' discovery also urges us to ask why motor abnormalities exist in typically developing infants when their parents present some subclinical ASD traits. We believe that there are at least two possibilities. In the first possible scenario, motor impairments and ASD traits form a single cluster of symptoms unique to a subgroup of individuals with autism. A second possible scenario is that motor atypicalities are the first warning signs of vulnerability often associated with atypical development. In conclusion, Chinello et al.'s findings inform us that subclinical atypical phenotypes such as sociocommunicative anomalies may be related to subclinical motor performances in the next generation. This adds to our knowledge by shedding some light on the relation of vulnerability in one domain with vulnerability in another domain.}, } @article {pmid27861757, year = {2017}, author = {Schlomer, GL and Cleveland, HH and Feinberg, ME and Wolf, PSA and Greenberg, MT and Spoth, RL and Redmond, C and Tricou, EP and Vandenbergh, DJ}, title = {Extending Previous cG×I Findings on 5-HTTLPR's Moderation of Intervention Effects on Adolescent Substance Misuse Initiation.}, journal = {Child development}, volume = {88}, number = {6}, pages = {2001-2012}, pmid = {27861757}, issn = {1467-8624}, support = {R01 DA013709/DA/NIDA NIH HHS/United States ; P50 DA010075/DA/NIDA NIH HHS/United States ; P50 DA039838/DA/NIDA NIH HHS/United States ; T32 DA017629/DA/NIDA NIH HHS/United States ; R01 DA030389/DA/NIDA NIH HHS/United States ; }, mesh = {Adolescent ; Adolescent Behavior/*psychology ; Child ; Female ; *Gene-Environment Interaction ; Humans ; Male ; *Risk-Taking ; Serotonin Plasma Membrane Transport Proteins/*genetics ; Substance-Related Disorders/*genetics/*psychology ; }, abstract = {This study addresses replication in candidate gene × environment interaction (cG×E) research by investigating if the key findings from Brody, Beach, Philibert, Chen, and Murry (2009) can be detected using data (N = 1,809) from the PROSPER substance use preventive intervention delivery system. Parallel to Brody et al., this study tested the hypotheses that substance misuse initiation would increase faster from age 11 to age 14 and be higher at age 14 among: (a) 5-HTTLPR short carrier adolescents versus long homozygotes, (b) control versus intervention adolescents, and (c) 5-HTTLPR short carriers in the control condition versus all other participants. The hypotheses were generally supported and results were consistent with Brody et al.'s cG×I finding. Results are discussed in light of replication issues in cG×E research and implications for intervention.}, } @article {pmid27859680, year = {2016}, author = {Kangaslampi, S and Punamäki, RL and Qouta, S and Diab, M and Peltonen, K}, title = {Psychosocial Group Intervention Among War-Affected Children: An Analysis of Changes in Posttraumatic Cognitions.}, journal = {Journal of traumatic stress}, volume = {29}, number = {6}, pages = {546-555}, doi = {10.1002/jts.22149}, pmid = {27859680}, issn = {1573-6598}, mesh = {Adolescent ; Arabs/psychology ; Case-Control Studies ; Child ; Depression/complications/psychology ; Disease Progression ; Exposure to Violence/*psychology ; Female ; Humans ; Male ; Psychosocial Support Systems ; Psychotherapy, Group/*statistics & numerical data ; Severity of Illness Index ; Stress Disorders, Traumatic/complications/psychology/*therapy ; Warfare ; }, abstract = {Cognitive theories point to reduction in dysfunctional posttraumatic cognitions (PTCs) as one mechanism involved in recovery from posttraumatic stress symptoms (PTSS), yet research findings have shown individual differences in the recovery process. We tested the cognitive mediation hypothesis above in a previously published psychosocial group intervention among war-affected children. We also examined heterogeneity in children's PTCs during the intervention. We used a cluster randomized trial of Smith et al.'s (2002) teaching recovery techniques (TRT) intervention among 482 Palestinians 10-13 years of age (n = 242 for intervention group, n = 240 for control group). Children reported PTSS, PTCs, and depressive symptoms at baseline, midpoint, postintervention, and at 6-month follow-up. Path analysis results showed that TRT was not effective in reducing dysfunctional PTCs, and the reductions did not mediate intervention effects on PTSS. Using latent class growth analysis, we chose the model with 3 differing trajectories in the intervention group: high, decreasing, moderate, downward trending, and severe, stable levels of PTCs. Higher PTSS and depressive symptoms at baseline were associated with membership in the severe, stable trajectory. The intervention did not produce the kind of beneficial cognitive change needed in the cognitive mediation conceptualization. Nevertheless, cognitive changes differed substantially across children during the intervention, and were associated with their preintervention mental health status. These findings call for more detailed examination of the process of cognitive mediation.}, } @article {pmid27859343, year = {2016}, author = {Melhem, NM and Brent, D}, title = {Commentary: The course of depression after childhood parental death - a reflection on Berg et al. (2016).}, journal = {Journal of child psychology and psychiatry, and allied disciplines}, volume = {57}, number = {12}, pages = {1467-1469}, pmid = {27859343}, issn = {1469-7610}, support = {K01 MH077930/MH/NIMH NIH HHS/United States ; R01 MH065368/MH/NIMH NIH HHS/United States ; }, mesh = {Depression/*epidemiology ; Depressive Disorder/epidemiology ; Humans ; Incidence ; Longitudinal Studies ; *Parental Death ; }, abstract = {Berg et al.'s study highlights the long-lasting impact of childhood parental death on depression in adulthood in the absence of early preventive and intervention efforts. Given the long-term effects of childhood parental death, it seems that the most propitious time to intervene is early on after the death. Several prevention and intervention approaches have been shown to reduce the incidence of depression and to ameliorate its course and thus could be potential approaches to intervene with parentally bereaved children. Future longitudinal studies focused on children and adolescents are also needed to examine the biological pathways that set the stage for increased vulnerability across the life span following childhood parental death and adversity in order to inform novel targets for interventions.}, } @article {pmid27841554, year = {2016}, author = {Dharuman, G and Verboncoeur, J and Christlieb, A and Murillo, MS}, title = {Atomic bound state and scattering properties of effective momentum-dependent potentials.}, journal = {Physical review. E}, volume = {94}, number = {4-1}, pages = {043205}, doi = {10.1103/PhysRevE.94.043205}, pmid = {27841554}, issn = {2470-0053}, abstract = {Effective classical dynamics provide a potentially powerful avenue for modeling large-scale dynamical quantum systems. We have examined the accuracy of a Hamiltonian-based approach that employs effective momentum-dependent potentials (MDPs) within a molecular-dynamics framework through studies of atomic ground states, excited states, ionization energies, and scattering properties of continuum states. Working exclusively with the Kirschbaum-Wilets (KW) formulation with empirical MDPs [C. L. Kirschbaum and L. Wilets, Phys. Rev. A 21, 834 (1980)0556-279110.1103/PhysRevA.21.834], optimization leads to very accurate ground-state energies for several elements (e.g., N, F, Ne, Al, S, Ar, and Ca) relative to Hartree-Fock values. The KW MDP parameters obtained are found to be correlated, thereby revealing some degree of transferability in the empirically determined parameters. We have studied excited-state orbits of electron-ion pair to analyze the consequences of the MDP on the classical Coulomb catastrophe. From the optimized ground-state energies, we find that the experimental first- and second-ionization energies are fairly well predicted. Finally, electron-ion scattering was examined by comparing the predicted momentum transfer cross section to a semiclassical phase-shift calculation; optimizing the MDP parameters for the scattering process yielded rather poor results, suggesting a limitation of the use of the KW MDPs for plasmas.}, } @article {pmid27837424, year = {2017}, author = {Kekwaletswe, CT and Jordaan, E and Nkosi, S and Morojele, NK}, title = {Social Support and the Mediating Roles of Alcohol Use and Adherence Self-Efficacy on Antiretroviral Therapy (ART) Adherence Among ART Recipients in Gauteng, South Africa.}, journal = {AIDS and behavior}, volume = {21}, number = {7}, pages = {1846-1856}, doi = {10.1007/s10461-016-1595-3}, pmid = {27837424}, issn = {1573-3254}, mesh = {Adolescent ; Adult ; Alcohol Drinking/*epidemiology ; Anti-HIV Agents/*therapeutic use ; Cross-Sectional Studies ; Depression/*epidemiology ; Female ; HIV Infections/*drug therapy ; Humans ; Male ; *Medication Adherence ; Middle Aged ; *Self Efficacy ; *Social Support ; South Africa ; Young Adult ; }, abstract = {We sought to (a) replicate and (b) extend (via the addition of alcohol use) Cha et al.'s cross-sectional multi-component model of ART adherence on the relationship between social support, depression, self-efficacy beliefs, and antiretroviral therapy (ART) adherence, among HIV patients in Tshwane, South Africa. Using purposive sampling, 304 male and female ART recipients were recruited. ART adherence was assessed using three manifest indicators: total adherence ratio, the CASE adherence index and 1-month adherence measure. Data were analysed using structural equation modeling. In our replicated model, social support had both direct and indirect relationships with ART adherence, and inclusion of alcohol use improved prediction of ART adherence. Direct and indirect effects of alcohol use on ART adherence emerged: adherence self-efficacy beliefs partially mediated the latter path. Findings highlight the importance of integrating into ART promotion interventions, the reduction of alcohol use, provision of social support, and enhancement of adherence self-efficacy beliefs.}, } @article {pmid27826272, year = {2016}, author = {Cunningham, MR and Baumeister, RF}, title = {How to Make Nothing Out of Something: Analyses of the Impact of Study Sampling and Statistical Interpretation in Misleading Meta-Analytic Conclusions.}, journal = {Frontiers in psychology}, volume = {7}, number = {}, pages = {1639}, pmid = {27826272}, issn = {1664-1078}, abstract = {The limited resource model states that self-control is governed by a relatively finite set of inner resources on which people draw when exerting willpower. Once self-control resources have been used up or depleted, they are less available for other self-control tasks, leading to a decrement in subsequent self-control success. The depletion effect has been studied for over 20 years, tested or extended in more than 600 studies, and supported in an independent meta-analysis (Hagger et al., 2010). Meta-analyses are supposed to reduce bias in literature reviews. Carter et al.'s (2015) meta-analysis, by contrast, included a series of questionable decisions involving sampling, methods, and data analysis. We provide quantitative analyses of key sampling issues: exclusion of many of the best depletion studies based on idiosyncratic criteria and the emphasis on mini meta-analyses with low statistical power as opposed to the overall depletion effect. We discuss two key methodological issues: failure to code for research quality, and the quantitative impact of weak studies by novice researchers. We discuss two key data analysis issues: questionable interpretation of the results of trim and fill and Funnel Plot Asymmetry test procedures, and the use and misinterpretation of the untested Precision Effect Test and Precision Effect Estimate with Standard Error (PEESE) procedures. Despite these serious problems, the Carter et al. (2015) meta-analysis results actually indicate that there is a real depletion effect - contrary to their title.}, } @article {pmid27822786, year = {2017}, author = {Schwartz, LP and Silberberg, A and Casey, AH and Kearns, DN and Slotnick, B}, title = {Does a rat release a soaked conspecific due to empathy?.}, journal = {Animal cognition}, volume = {20}, number = {2}, pages = {299-308}, pmid = {27822786}, issn = {1435-9456}, support = {R15 MH109922/MH/NIMH NIH HHS/United States ; }, mesh = {Animals ; *Empathy ; Rats ; Rats, Sprague-Dawley ; *Social Behavior ; }, abstract = {In Experiment 1, rats choosing in an E maze preferred to release a rat standing in a pool of water to dry ground over a rat already standing on dry ground. Five additional experiments showed that the choosing rat's preference for releasing the wet rat was maintained by two separable outcomes: (1) the social contact offered by the released rat and (2) the reinforcing value of proximity to a pool of water. These results call into question Sato et al.'s (Anim Cogn 18:1039-1047, 2015) claim to have demonstrated that a rat's releasing of a wet rat to dry ground is empathically motivated.}, } @article {pmid27822568, year = {2016}, author = {Bang, H}, title = {Random Guess and Wishful Thinking are the Best Blinding Scenarios.}, journal = {Contemporary clinical trials communications}, volume = {3}, number = {}, pages = {117-121}, pmid = {27822568}, issn = {2451-8654}, support = {UL1 TR000002/TR/NCATS NIH HHS/United States ; }, abstract = {Blinding is a methodologic safeguard of treatment evaluation, yet severely understudied empirically. Mathieu et al.'s theoretical analysis (2014) provided an important message that blinding cannot eliminate potential for bias associated with belief about allocation in randomized controlled trial; just like the intent-to-treat principle does not guarantee unbiased estimation under noncompliance, the blinded randomized trial as a golden standard may produce bias. They showed possible biases but did not assess how large the bias could be in different scenarios. In this paper, we examined their findings, and numerically assessed and compared the bias in treatment effect parameters by simulation under frequently encountered blinding scenarios, aiming to identify the most ideal blinding scenarios in practice. We conclude that Random Guess and Wishful Thinking (e.g., participants tend to believe they received treatment) are the most ideal blinding scenarios, incurring minimal bias. We also find some evidence that imperfect or partial blinding can be better than no blinding.}, } @article {pmid27816574, year = {2017}, author = {Huang, ZY and Kraus, VB}, title = {Reply to Stausholm et al.'s letter to the editor regarding our published study entitled, "Effectiveness of low-level laser therapy in patients with knee osteoarthritis: a systematic review and meta-analysis".}, journal = {Osteoarthritis and cartilage}, volume = {25}, number = {4}, pages = {e11-e14}, doi = {10.1016/j.joca.2016.10.015}, pmid = {27816574}, issn = {1522-9653}, mesh = {Humans ; *Low-Level Light Therapy ; *Osteoarthritis, Knee ; }, } @article {pmid27816080, year = {2016}, author = {Piccirillo, ML and Taylor Dryman, M and Heimberg, RG}, title = {Safety Behaviors in Adults With Social Anxiety: Review and Future Directions.}, journal = {Behavior therapy}, volume = {47}, number = {5}, pages = {675-687}, doi = {10.1016/j.beth.2015.11.005}, pmid = {27816080}, issn = {1878-1888}, mesh = {Adult ; *Attitude to Health ; Female ; Humans ; Male ; Phobia, Social/*therapy ; Phobic Disorders/*therapy ; Safety ; Self Concept ; *Social Adjustment ; Social Behavior ; }, abstract = {Safety behaviors are considered an important factor in the maintenance of social anxiety disorder (SAD). Safety behaviors are typically employed by socially anxious individuals to reduce anxiety in feared social situations. However, by preventing individuals with social anxiety from gathering evidence that would disconfirm their maladaptive beliefs about social situations, the use of safety behaviors ultimately maintains social anxiety over time. Twenty years ago, Wells and colleagues (1995) demonstrated that use of safety behaviors diminishes the efficacy of exposure treatment for SAD, suggesting that reduction in the use of safety behaviors during exposure can enhance treatment response. Research on safety behaviors has expanded considerably since Wells et al.'s seminal publication, and our understanding of the role safety behaviors may play in the maintenance of social anxiety has grown in breadth and depth. In this paper, we present a detailed review of the published research on safety behaviors relevant to social anxiety and social-anxiety-related processes. Finally, we evaluate the impact of safety behaviors on the outcome of treatment for SAD, and we look to the literature on safety behaviors in other anxiety disorders to inform our understanding of use of safety behaviors during exposure and to facilitate future research in SAD.}, } @article {pmid27808394, year = {2016}, author = {Han, JC and Zhang, YJ and Li, XD}, title = {Retraction RETRACTION of "Association between polymorphisms in the XRCC1 gene and the risk of non-small cell lung cancer", by Han JC, Zhang YJ and Li XD - Genet. Mol. Res. 14 (4): 12888-12893 (2015).}, journal = {Genetics and molecular research : GMR}, volume = {15}, number = {4}, pages = {}, doi = {10.4238/gmr.150462131}, pmid = {27808394}, issn = {1676-5680}, abstract = {The retracted article is: Han JC, Zhang YJ and Li XD (2015). Association between polymorphisms in the XRCC1 gene and the risk of non-small cell lung cancer. Genet. Mol. Res. 14: 12888-12893. The GMR editorial staff was alerted about this article (received on May 3, 2015; accepted on August 18, 2015) published on October 21, 2015 (DOI: 10.4238/2015.October.21.9) that was found to be substantially similar to the publication of "Association of XRCC1 gene polymorphisms with risk of non-small cell lung cancer" (received on January 25, 2015; accepted on March 23, 2015; e-published on April 1, 2015) by Kang et al., published in the International Journal of Clinical Experimental Pathology 8 (4): 4171-4176. The authors were aware of the Kang et al.'s paper, since they cite it several times in the manuscript published in GMR. Some of the language is similar between the two manuscripts, but what is the most concerning is that several of the tables in the papers are nearly identical. Tables 2 and 3 are exactly identical between the two articles, suggesting that the publication in GMR was plagiarized from the publication in the International Journal of Clinical Experimental Pathology. The Publisher and Editor decided to retract these articles in accordance with the recommendations of the Committee on Publication Ethics (COPE). After a thorough investigation, we have strong reason to believe that the peer review process was failure and, after review and contacting the authors, the editors of Genetics and Molecular Research decided to retract the article. The authors and their institutions were advised of this serious breach of ethics.}, } @article {pmid27480160, year = {2016}, author = {Kroneisen, M and Rummel, J and Erdfelder, E}, title = {What kind of processing is survival processing? : Effects of different types of dual-task load on the survival processing effect.}, journal = {Memory & cognition}, volume = {44}, number = {8}, pages = {1228-1243}, pmid = {27480160}, issn = {1532-5946}, mesh = {Adolescent ; Adult ; Executive Function/*physiology ; Female ; Humans ; Male ; *Memory, Episodic ; Memory, Short-Term/*physiology ; Survival ; Young Adult ; }, abstract = {Words judged for their relevance in a survival context are remembered better than words processed in non-survival contexts. This phenomenon is known as the survival processing effect. Recently, inconsistent results were reported on whether the size of the survival processing effect is affected by cognitive load. Whereas Kroneisen, Rummel, and Erdfelder (Memory 22: 92-102, 2014) observed that the survival processing effect vanishes under dual-task conditions, Stillman, Coane, Profaci, Howard, and Howard (Memory & Cognition 42: 175-185, 2014, Experiment 1) found that the size of survival processing effect is essentially unaffected by a cognitively demanding secondary task. In three experiments, we investigated the differences between these studies to achieve a better understanding of dual-task effects on the survival-processing advantage. In the first experiment, we replicated Stillman et al.'s results using their dual-task conditions combined with a sample more than twice as large as theirs. In the second experiment, we compared dual-task conditions that differed regarding how strongly the secondary task taxed (a) working memory load (maintenance of one vs. several items) and (b) processing demands (switching vs. time-sharing between tasks). A third experiment focussed on low (i.e., single-item) load under time-sharing processing conditions. Results consistently showed that the survival processing effect persisted under low load but vanished when the number of items held in working memory increased beyond one, irrespective of processing demands. Implications of these findings for explanations of the survival-processing advantage are discussed.}, } @article {pmid27630161, year = {2016}, author = {Myung, SK}, title = {Erroneous conclusions about the association between light alcohol drinking and the risk of cancer: comments on Bagnardi et al.'s meta-analysis.}, journal = {Annals of oncology : official journal of the European Society for Medical Oncology}, volume = {27}, number = {11}, pages = {2138}, doi = {10.1093/annonc/mdw294}, pmid = {27630161}, issn = {1569-8041}, mesh = {*Alcohol Drinking ; Humans ; *Neoplasms ; Risk ; Risk Factors ; }, } @article {pmid27621278, year = {2016}, author = {Bagnardi, V and Botteri, E and La Vecchia, C}, title = {Reply to the letter to the editor 'Erroneous conclusions about the association between light alcohol drinking and the risk of cancer: comments on Bagnardi et al.'s meta-analysis, by S.-K. Myung'.}, journal = {Annals of oncology : official journal of the European Society for Medical Oncology}, volume = {27}, number = {11}, pages = {2138-2139}, doi = {10.1093/annonc/mdw295}, pmid = {27621278}, issn = {1569-8041}, mesh = {*Alcohol Drinking ; Humans ; *Neoplasms ; Risk ; }, } @article {pmid27373211, year = {2016}, author = {Kuonen, F and Aschwanden, J and Dimaio, DJ and Elston, DM and Gilliet, M and Hohl, D and Gaide, O}, title = {Colonisation of basal cell carcinoma by lentigo maligna: a case report, review of the literature, and series follow-up.}, journal = {European journal of dermatology : EJD}, volume = {26}, number = {5}, pages = {465-469}, doi = {10.1684/ejd.2016.2820}, pmid = {27373211}, issn = {1952-4013}, mesh = {Aged ; Carcinoma, Basal Cell/chemistry/*pathology ; Eyelid Neoplasms/chemistry/*pathology ; Female ; Humans ; Hutchinson's Melanotic Freckle/chemistry/*pathology ; Neoplasms, Complex and Mixed/chemistry/*pathology ; Skin Neoplasms/chemistry/*pathology ; }, abstract = {BACKGROUND: Melanocytic tumours which colonise basal cell carcinomas (BCC) may be considered as either lentigo maligna (LM) (in situ) or invasive melanomas.

OBJECTIVES: To highlight the diagnostic approach and long-term prognosis of LM which colonises BCC.

MATERIALS AND METHODS: Using Satter et al.'s classification, we identified a case of BCC colonised by LM and reviewed similar cases in the literature with long-term follow-up.

RESULTS: In the absence of melanocytic extension beyond the lamina propria of the BCC compartment, mixed tumours may be considered as LM colonising the BCC, allowing for less invasive surgery. The absence of long-term relapse in our short series supports this diagnosis, rather than invasive melanomas.

CONCLUSION: Our case report, review of the literature, and series follow-up illustrate the most recent assessment of melanocytic/BCC tumours, and guide the physician and the pathologist in their recognition and classification, thus allowing them to make the most appropriate therapeutic decisions.}, } @article {pmid26954726, year = {2017}, author = {Gračanin, A and van Assen, MA and Omrčen, V and Koraj, I and Vingerhoets, AJ}, title = {Chemosignalling effects of human tears revisited: Does exposure to female tears decrease males' perception of female sexual attractiveness?.}, journal = {Cognition & emotion}, volume = {31}, number = {1}, pages = {139-150}, doi = {10.1080/02699931.2016.1151402}, pmid = {26954726}, issn = {1464-0600}, mesh = {Adolescent ; Adult ; Arousal ; Double-Blind Method ; Humans ; *Inhibition, Psychological ; Male ; Olfactory Perception ; *Sexual Behavior ; *Tears ; Visual Perception ; Young Adult ; }, abstract = {Gelstein et al. reported the results of three experiments suggesting a dampening influence of inhalation of female emotional tears on males' arousal and perception of female sexual attractiveness, specifically in non-sexual situations. This prompted the hypothesis that crying exerts its influence on others not only via the auditory and visual mode but also via chemosignals. In three studies, we attempted to replicate and extend Gelstein et al.'s findings by including an additional condition with irritant tears, by using pictures of sexually attractive women, and by testing related hypotheses on the pro-social effects of exposure to tears. All three studies, separately or combined in a meta-analysis, failed to replicate the original inhibitory effects of tears. In addition, sniffing tears did not affect measures of connectedness, aggression and pro-social behaviour. It is concluded that the effects of female tears on male arousal and perception of female sexual attractiveness, if any, are very weak at best. Rather, it seems that crying exerts its strong inter-personal effects through the visual and auditory sensory channels.}, } @article {pmid27775411, year = {2018}, author = {Hamilton, RKB and Newman, JP}, title = {Information processing capacity in psychopathy: Effects of anomalous attention.}, journal = {Personality disorders}, volume = {9}, number = {2}, pages = {182-187}, pmid = {27775411}, issn = {1949-2723}, support = {R21 DA030876/DA/NIDA NIH HHS/United States ; }, mesh = {Adult ; Antisocial Personality Disorder/complications/*physiopathology ; Attention/*physiology ; Cognitive Dysfunction/etiology/*physiopathology ; Humans ; Male ; Middle Aged ; Pattern Recognition, Visual/*physiology ; Prisoners ; Psychomotor Performance/*physiology ; Space Perception/*physiology ; Young Adult ; }, abstract = {Hamilton and colleagues (2015) recently proposed that an integrative deficit in psychopathy restricts simultaneous processing, thereby leaving fewer resources available for information encoding, narrowing the scope of attention, and undermining associative processing. The current study evaluated this parallel processing deficit proposal using the Simultaneous-Sequential paradigm. This investigation marks the first a priori test of the Hamilton et al.'s theoretical framework. We predicted that psychopathy would be associated with inferior performance (as indexed by lower accuracy and longer response time) on trials requiring simultaneous processing of visual information relative to trials necessitating sequential processing. Results were consistent with these predictions, supporting the proposal that psychopathy is characterized by a reduced capacity to process multicomponent perceptual information concurrently. We discuss the potential implications of impaired simultaneous processing for the conceptualization of the psychopathic deficit. (PsycINFO Database Record}, } @article {pmid27781970, year = {2017}, author = {McKenna, P and Thoma, B and Milne, K and Bond, C}, title = {SGEM Hot Off the Press: ultrasound during critical care simulation: a randomized crossover study.}, journal = {CJEM}, volume = {19}, number = {1}, pages = {50-54}, doi = {10.1017/cem.2016.380}, pmid = {27781970}, issn = {1481-8043}, mesh = {*Blogging ; Canada ; Clinical Competence ; *Critical Care ; Cross-Over Studies ; Emergency Medicine/education ; Emergency Service, Hospital ; Female ; Humans ; Male ; *Point-of-Care Systems ; *Quality Assurance, Health Care ; Simulation Training/*methods ; Ultrasonography/*methods ; }, abstract = {As part of the Canadian Journal of Emergency Medicine's (CJEM) developing social media strategy, 1 we are collaborating with the Skeptics' Guide to Emergency Medicine (SGEM) to summarize and critically appraise the current emergency medicine (EM) literature using evidence-based medicine principles. In the "Hot Off the Press" series, we select original research manuscripts published in CJEM to be featured on the SGEM website/podcast 2 and discussed by the study authors and the online EM community. A similar collaboration is underway between the SGEM and Academic Emergency Medicine. What follows is a summary of the selected article the immediate post-publication synthesis from the SGEM podcast, commentary by the first author, and the subsequent discussion from the SGEM blog and other social media. Through this series, we hope to enhance the value, accessibility, and application of important, clinically relevant EM research. In this, the third SGEM HOP hosted collaboratively with CJEM, we discuss Olszynski et al.'s randomized crossover study evaluating the use of ultrasound simulator devices during critical care simulation. 3.}, } @article {pmid27650009, year = {2016}, author = {Gysels, M and Reilly, CC and Jolley, CJ and Pannell, C and Spoorendonk, F and Moxham, J and Bausewein, C and Higginson, IJ}, title = {Dignity Through Integrated Symptom Management: Lessons From the Breathlessness Support Service.}, journal = {Journal of pain and symptom management}, volume = {52}, number = {4}, pages = {515-524}, doi = {10.1016/j.jpainsymman.2016.04.010}, pmid = {27650009}, issn = {1873-6513}, support = {MCCC-RP-15-A18859/MCCC_/Marie Curie/United Kingdom ; PB-PG-0808-17311/DH_/Department of Health/United Kingdom ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Cross-Sectional Studies ; Disease Management ; Dyspnea/*psychology/*therapy ; Female ; Humans ; Interviews as Topic ; Male ; Middle Aged ; Models, Psychological ; *Palliative Care ; Personhood ; Qualitative Research ; Social Stigma ; }, abstract = {CONTEXT: Dignity is poorly conceptualized and little empirically explored in end-of-life care. A qualitative evaluation of a service offering integrated palliative and respiratory care for patients with advanced disease and refractory breathlessness uncovered an unexpected outcome, it enhanced patients' dignity.

OBJECTIVES: To analyze what constitutes dignity for people suffering from refractory breathlessness with advanced disease, and its implications for the concept of dignity.

METHODS: Qualitative study of cross-sectional interviews with 20 patients as part of a Phase III evaluation of a randomized controlled fast-track trial. The interviews were transcribed verbatim, imported into NVivo, and analyzed through constant comparison. The findings were compared with Chochinov et al.'s dignity model. The model was adapted with the themes and subthemes specific to patients suffering from breathlessness.

RESULTS: The findings of this study underscore the applicability of the conceptual model of dignity for patients with breathlessness. There were many similarities in themes and subthemes. Differences specifically relevant for patients suffering from severe breathlessness were as follows: 1) physical distress and psychological mechanisms are interlinked with the disability and dependence breathlessness causes, in the illness-related concerns, 2) stigma is an important component of the social dignity inventory, 3) conditions and perspectives need to be present to practice self-care in the dignity-conserving repertoire.

CONCLUSION: Dignity is an integrated concept and can be affected by influences from other areas such as illness-related concerns. The intervention shows that targeting the symptom holistically and equipping patients with the means for self-care realized the outcome of dignity.}, } @article {pmid27755551, year = {2016}, author = {Lei, X and Chen, C and Chen, C and He, Q and Moyzis, RK and Xue, G and Dong, Q}, title = {Striatum-Centered Fiber Connectivity Is Associated with the Personality Trait of Cooperativeness.}, journal = {PloS one}, volume = {11}, number = {10}, pages = {e0162160}, pmid = {27755551}, issn = {1932-6203}, mesh = {Amygdala/physiology ; Brain/diagnostic imaging ; *Cooperative Behavior ; Corpus Striatum/*physiology ; Female ; Gyrus Cinguli/physiology ; Hippocampus/physiology ; Humans ; Image Processing, Computer-Assisted ; Magnetic Resonance Imaging ; Male ; Neural Pathways/*physiology ; *Personality ; Prefrontal Cortex/physiology ; Young Adult ; }, abstract = {Cooperativeness is an essential behavioral trait evolved to facilitate group living. Social and cognitive mechanisms involved in cooperation (e.g., motivation, reward encoding, action evaluation, and executive functions) are sub-served by the striatal-projected circuits, whose physical existence has been confirmed by animal studies, human postmortem studies, and in vivo human brain studies. The current study investigated the associations between Cooperativeness and fiber connectivities from the striatum to nine subcortical and cortical regions, including the amygdala, hippocampus, medial orbitofrontal cortex, lateral orbitofrontal cortex, ventrolateral prefrontal cortex, dorsolateral prefrontal cortex, posterior cingulate cortex/retrosplenial cortex, dorsal cingulate cortex, and rostral cingulate cortex. Results showed that Cooperativeness was negatively correlated with fiber connectivity for the cognitive control system (from the dorsal caudate to the rostral cingulate cortex and ventrolateral prefrontal cortex), but not with fiber connectivity for the social cognitive system (e.g., connectivity with the medial prefrontal cortex and amygdala). These results partially supported Declerck et al.'s (2013) cognitive neural model of the role of cognitive control and social cognition in cooperation.}, } @article {pmid27742915, year = {2016}, author = {Arnett, P}, title = {Lubrini et al.'s study, "The contribution of depressive symptoms to slowness of information processing in relapsing remitting multiple sclerosis".}, journal = {Multiple sclerosis (Houndmills, Basingstoke, England)}, volume = {22}, number = {12}, pages = {1512-1513}, doi = {10.1177/1352458516672018}, pmid = {27742915}, issn = {1477-0970}, mesh = {Cognition ; *Depression ; Disability Evaluation ; Humans ; *Multiple Sclerosis ; Multiple Sclerosis, Relapsing-Remitting ; }, } @article {pmid27739417, year = {2016}, author = {Chung, Y and Choi, S and Lee, Y and Park, N and Won, D}, title = {An Enhanced Lightweight Anonymous Authentication Scheme for a Scalable Localization Roaming Service in Wireless Sensor Networks.}, journal = {Sensors (Basel, Switzerland)}, volume = {16}, number = {10}, pages = {}, pmid = {27739417}, issn = {1424-8220}, abstract = {More security concerns and complicated requirements arise in wireless sensor networks than in wired networks, due to the vulnerability caused by their openness. To address this vulnerability, anonymous authentication is an essential security mechanism for preserving privacy and providing security. Over recent years, various anonymous authentication schemes have been proposed. Most of them reveal both strengths and weaknesses in terms of security and efficiency. Recently, Farash et al. proposed a lightweight anonymous authentication scheme in ubiquitous networks, which remedies the security faults of previous schemes. However, their scheme still suffers from certain weaknesses. In this paper, we prove that Farash et al.'s scheme fails to provide anonymity, authentication, or password replacement. In addition, we propose an enhanced scheme that provides efficiency, as well as anonymity and security. Considering the limited capability of sensor nodes, we utilize only low-cost functions, such as one-way hash functions and bit-wise exclusive-OR operations. The security and lightness of the proposed scheme mean that it can be applied to roaming service in localized domains of wireless sensor networks, to provide anonymous authentication of sensor nodes.}, } @article {pmid27737737, year = {2017}, author = {Baudouin, A and Armoiry, X and Dussart, C}, title = {[Medico-economic evaluation of therapeutic strategies at hospital: A systematic review of French studies].}, journal = {Annales pharmaceutiques francaises}, volume = {75}, number = {3}, pages = {227-235}, doi = {10.1016/j.pharma.2016.09.002}, pmid = {27737737}, issn = {0003-4509}, mesh = {Cost-Benefit Analysis ; Diagnosis ; *Economics, Hospital ; France ; Health Expenditures/*statistics & numerical data ; Humans ; }, abstract = {INTRODUCTION: Therapeutic innovation contributes to the increase of health care expenditures in France. Medico-economic evaluation has still a minor role in the decision-making for the registration of drugs and medical devices in hospitals. This study aimed to systematically review published works on medico-economic studies conducted within French hospitals.

METHODS: A literature review was carried out to search for medico-economic studies conducted by hospital teams on therapeutic or diagnostic strategies employed within French hospitals and published from 2010 to 2014. Quality assessment of selected studies was performed according to Drummond et al.'s checklist, which is also used within French guidelines.

RESULTS: Of the 44 analyzed articles, methods for identification and measure of costs and results complied with guidelines in 95 % of cases. For results interpretation, compliance was 91 %. Costs discounting (29 %) and the use of sensitivity analysis to account for results uncertainty (70 %) were the parameters with the lowest compliance to guidelines.

CONCLUSION: A good training of health professionals in using economic and statistic tools, and the transferability of results of medico-economic studies are essential and should be optimized to enable a broader use of medico-economic evaluation within the scope of decision-making in French hospitals.}, } @article {pmid27733974, year = {2016}, author = {Ghasempour Nesheli, A and Mirjalili, A and Yazdanpanah, MM}, title = {Numerical solution of DGLAP equations using Laguerre polynomials expansion and Monte Carlo method.}, journal = {SpringerPlus}, volume = {5}, number = {1}, pages = {1672}, pmid = {27733974}, issn = {2193-1801}, abstract = {We investigate the numerical solutions of the DGLAP evolution equations at the LO and NLO approximations, using the Laguerre polynomials expansion. The theoretical framework is based on Furmanski et al.'s articles. What makes the content of this paper different from other works, is that all calculations in the whole stages to extract the evolved parton distributions, are done numerically. The employed techniques to do the numerical solutions, based on Monte Carlo method, has this feature that all the results are obtained in a proper wall clock time by computer. The algorithms are implemented in FORTRAN and the employed coding ideas can be used in other numerical computations as well. Our results for the evolved parton densities are in good agreement with some phenomenological models. They also indicate better behavior with respect to the results of similar numerical calculations.}, } @article {pmid27733936, year = {2015}, author = {Månsson, C and Nilsson, A and Månsson, D and Karlson, BM}, title = {Response from the authors of the original article. Comment to: Månsson C, Nilsson A, Karlson B-M. Severe complications with irreversible electroporation of the pancreas in the presence of a metallic stent: a warning of a procedure that never should be performed: Regarding Scheffer, Voge, van den Bos et al.'s comments.}, journal = {Acta radiologica open}, volume = {4}, number = {9}, pages = {2058460115603876}, pmid = {27733936}, issn = {2058-4601}, } @article {pmid27715474, year = {2016}, author = {Wu, DB and Lee, KK and Lee, VW and Hong, LW}, title = {Reply to Varghese et al.'s response to Wu et al. - "Cost effectiveness analysis of infant pneumococcal vaccination in Malaysia and Hong Kong".}, journal = {Human vaccines & immunotherapeutics}, volume = {12}, number = {10}, pages = {2681-2684}, pmid = {27715474}, issn = {2164-554X}, mesh = {*Cost-Benefit Analysis ; Hong Kong ; Humans ; Infant ; Malaysia ; Pneumococcal Infections ; Pneumococcal Vaccines ; *Vaccination ; }, } @article {pmid27709627, year = {2016}, author = {de Timary, P and Maurage, P}, title = {Considering Cognitive Mentalizing Deficits as a Transient and Reversible Impairment in Alcohol Dependence: A Response to Fein's Commentary on Maurage et al.'s Paper.}, journal = {Alcoholism, clinical and experimental research}, volume = {40}, number = {12}, pages = {2692-2693}, doi = {10.1111/acer.13244}, pmid = {27709627}, issn = {1530-0277}, mesh = {*Alcoholism ; Cognition ; Cognition Disorders ; Cognitive Dysfunction ; Humans ; *Theory of Mind ; }, } @article {pmid27708817, year = {2016}, author = {Guo, P and Watts, K and Wharrad, H}, title = {An integrative review of the impact of mobile technologies used by healthcare professionals to support education and practice.}, journal = {Nursing open}, volume = {3}, number = {2}, pages = {66-78}, pmid = {27708817}, issn = {2054-1058}, abstract = {AIM: The aim of this study was to provide evidence of the impact of mobile technologies among healthcare professionals in education and practice settings.

DESIGN: Integrative literature review.

METHODS: Electronic databases including MEDLINE, CINAHL, PsycINFO, EMBASE, ERIC and Web of Science were searched for papers published between 2002-2012. Quantitative studies were critically evaluated based on Thomas et al.'s framework, while the consolidated criteria for reporting qualitative research was used to appraise the rigour of the qualitative studies.

RESULTS: Seventeen quantitative and three qualitative studies were included. The findings suggest a largely positive influence of mobile technologies on various clinical practice and educational outcomes. However, robust evidence was limited. Use of mobile technologies in health care are associated with improvements in access to information, accuracy and efficiency, evidence-based decision making at the point of care and enhancement in performance, confidence and engagement in different contexts.}, } @article {pmid27703910, year = {2015}, author = {Maguire, RW and Allen, RF}, title = {Another Perspective on Research as a Measure of High-Quality Practitioner Training: a Response to Dixon, Reed, Smith, Belisle, and Jackson.}, journal = {Behavior analysis in practice}, volume = {8}, number = {2}, pages = {154-155}, pmid = {27703910}, issn = {1998-1929}, abstract = {Dixon et al. (Behavior Analysis in Practice 8:7-15, 2015) argued that the research productivity of behavior analytic graduate programs may be a reasonable criterion to evaluate training program quality. They reviewed the cumulative publications of graduate programs. From this analysis, they generated a top ten list of graduate programs with the greatest number of faculty publications and, because of the number of these publications, inferred that they may be better training programs than those not on the list. We countered that the quality of graduate training programs is evident in the behavior of those who are trained, and thus, our field's interest should focus on determining the degree to which individual program graduates-and not their faculty-have mastered the research process. Thus, we proposed including student authors' work as an alternative to Dixon et al.'s analysis.}, } @article {pmid27703426, year = {2016}, author = {Kahlenberg, CA and Dare, DM and Dines, JS}, title = {Further Research Is Needed to Define the Benefits of Non-operative Rotator Cuff Treatment.}, journal = {HSS journal : the musculoskeletal journal of Hospital for Special Surgery}, volume = {12}, number = {3}, pages = {291-294}, pmid = {27703426}, issn = {1556-3316}, abstract = {Kukkonen et al.'s "Treatment of Nontraumatic Rotator Cuff Tears: A Randomized Controlled Trial with Two Years of Clinical and Imaging Follow-up" compared the efficacy of physical therapy, acromioplasty, and rotator cuff repair for the treatment of degenerative supraspinatus tendon tears in patients aged over 55. This review examines the authors' findings and their implications on clinical practice. Kukkonen et al. reported no significant difference in clinical outcome among patients treated operatively versus non-operatively for degenerative rotator cuff tears. The authors concluded that non-operative treatment is an appropriate option for patients aged 55 or older. Rotator cuff treatment outcomes are closely linked to patient age, and while this level I study found no evidence of a benefit of surgical treatment, the age range in the studied demographic was perhaps too wide to draw generalizable conclusions. Furthermore, 2-year follow-up may be inadequate to fully demonstrate the differences in outcomes between these treatment options.}, } @article {pmid27690513, year = {2016}, author = {Delaney, PF and Ericsson, KA}, title = {Long-term working memory and transient storage in reading comprehension: What is the evidence? Comment on Foroughi, Werner, Barragán, and Boehm-Davis (2015).}, journal = {Journal of experimental psychology. General}, volume = {145}, number = {10}, pages = {1406-1409}, doi = {10.1037/xge0000181}, pmid = {27690513}, issn = {1939-2222}, mesh = {*Comprehension ; Memory, Long-Term ; Memory, Short-Term ; *Reading ; }, abstract = {In a recent article, Foroughi, Werner, Barragán, and Boehm-Davis (2015) demonstrated that interspersing interruptions between paragraphs during reading sometimes reduces accuracy on comprehension questions. We propose an account of their findings within long-term working memory (LTWM) theory. Our account proposes that interruptions interfere with the accessibility of the generated encodings of the text in long-term memory (LTM) and that unimpaired continued comprehension requires restoration of access to these memory encodings during the resumption of reading after the interruptions. It is consistent with the accuracy of question answering being substantially preserved in their study, which is seemingly inconsistent with their transient storage account. This theoretical controversy does not diminish the importance of Foroughi et al.'s results: We agree that additional research is needed to understand when and how interruptions impact various aspects of comprehension. (PsycINFO Database Record}, } @article {pmid27681391, year = {2016}, author = {Nuvvula, S and Bhumireddy, JR and Kamatham, R and Mallineni, SK}, title = {Diagnostic accuracy of direct digital radiography and conventional radiography for proximal caries detection in primary teeth: A systematic review.}, journal = {Journal of the Indian Society of Pedodontics and Preventive Dentistry}, volume = {34}, number = {4}, pages = {300-305}, doi = {10.4103/0970-4388.191406}, pmid = {27681391}, issn = {1998-3905}, mesh = {Dental Caries/*diagnosis/*diagnostic imaging ; Humans ; Observer Variation ; Radiography, Bitewing/methods ; Radiography, Dental, Digital/*methods ; Sensitivity and Specificity ; Tooth, Deciduous/*diagnostic imaging ; }, abstract = {OBJECTIVE: The present study was conducted to uncover the diagnostic accuracy of digital versus conventional radiographic methods for the detection of proximal caries in primary teeth.

METHODS: Two researchers independently involved in the search process to explore Medical Subject Heading terms "dental digital radiography," "dental radiography," "bitewing," "dental caries," and "primary teeth" using PubMed, Cochrane Library, Ovid SP, and SIGLE databases. Search was confined to the articles published in English language only, with time period limit January 1996 to April 2014 and a hand search was performed to retrieve additional citations. Explicit inclusion and exclusion criteria were applied to eliminate undesired studies. Critical appraisal of the retrieved articles was done using the quality rating based on Bader and co-workers criteria.

RESULTS: A total of 129 articles were retrieved, among which 4 articles were included. All the four studies included were in vitro, of which two studies attained a high-quality score, whereas the other two attained average, and low scores based on Bader et al.'s criteria.

CONCLUSIONS: A big lacuna exists in the literature, regarding the evaluation of radiographic systems in primary teeth, suggesting an immediate need for well conducted in vivo studies. The quality of available evidence can be regarded as fair but cannot be suggested to set a baseline, indicating a need to perform high-quality studies in a randomized sample to find out the accuracy of digital and conventional radiographs.}, } @article {pmid27677298, year = {2017}, author = {MacFarlane, A and Galvin, R and O'Sullivan, M and McInerney, C and Meagher, E and Burke, D and LeMaster, JW}, title = {Participatory methods for research prioritization in primary care: an analysis of the World Café approach in Ireland and the USA.}, journal = {Family practice}, volume = {34}, number = {3}, pages = {278-284}, pmid = {27677298}, issn = {1460-2229}, mesh = {Community-Based Participatory Research/*methods ; Female ; Humans ; Ireland ; Patient Participation ; *Primary Health Care ; *Research ; Retrospective Studies ; United States ; }, abstract = {BACKGROUND: There are increasing imperatives for patients and members of the public to engage as partners in identifying health research priorities. The use of participatory methods to engage stakeholders in health care in research prioritization is not commonly reported.

OBJECTIVE: This article analyses the use of World Cafés as a participatory method for research prioritization with marginalized communities in Ireland and the USA.

METHODS: The principles of purposeful and snowball sampling were followed in both settings and a diverse range of community and health care stakeholders participated (n = 63 Ireland and n = 55 USA). The principles for a classic World Café were employed but there were novel features in each setting as well. Stewart et al.'s (Patients' and clinicians' research priorities. Health Expect 2011; 14: 439-48, conceptual framework for patient engagement was adapted and used to comparatively analyse the strengths and weaknesses of the World Cafés, focusing on agenda setting, engagement with research processes, interactional features and outputs.

RESULTS: Design principles for World Cafés were found to align with high-quality patient engagement for research prioritization in both settings. They served to facilitate meaningful collaboration among stakeholder groups in research prioritization (research agenda setting) and explored research priorities (engagement with research). The café ambience, emphasis on hospitality and self-facilitation created an environment for dialogues within and across participating groups (interactional features). There was a commitment to follow-up actions with reference to possible subsequent research (outputs).

CONCLUSIONS: The World Café is a valuable, participatory, flexible method that can be used with community and health care stakeholders for research prioritization with marginalized communities.}, } @article {pmid27669137, year = {2016}, author = {Kurtz, MJ and Starbird, LE}, title = {Interprofessional Clinical Ethics Education: The Promise of Cross-Disciplinary Problem-Based Learning.}, journal = {AMA journal of ethics}, volume = {18}, number = {9}, pages = {917-924}, doi = {10.1001/journalofethics.2016.18.9.nlit1-1609}, pmid = {27669137}, issn = {2376-6980}, mesh = {Attitude of Health Personnel ; *Cooperative Behavior ; *Curriculum ; Education, Medical ; Education, Nursing ; Education, Professional/*methods ; Ethics, Clinical/*education ; *Health Personnel/education/ethics ; Humans ; *Interprofessional Relations ; Patient Care ; Patient Care Team ; Pilot Projects ; *Problem-Based Learning ; Students, Medical ; Students, Nursing ; Taiwan ; }, abstract = {A review of Lin et al.'s pilot study exploring the effects of an interprofessional, problem-based learning clinical ethics curriculum on Taiwanese medical and nursing students' attitudes towards interprofessional collaboration highlights the benefits of interprofessional collaboration and offers insight into how problem-based learning might be universally applied in ethics education. Interprofessional collaboration is an ideal approach for exploring ethical dilemmas because it involves all relevant professionals in discussions about ethical values that arise in patient care. Interprofessional ethics collaboration is challenging to implement, however, given time constraints and organizational and practice demands. Nevertheless, we suggest that when professionals collaborate, they can collectively express greater commitment to the patient. We also suggest future research avenues that can explore additional benefits of interprofessional collaboration in clinical ethics.}, } @article {pmid27665111, year = {2016}, author = {Arshad, H and Rasoolzadegan, A}, title = {Design of a Secure Authentication and Key Agreement Scheme Preserving User Privacy Usable in Telecare Medicine Information Systems.}, journal = {Journal of medical systems}, volume = {40}, number = {11}, pages = {237}, pmid = {27665111}, issn = {1573-689X}, mesh = {Computer Security/*instrumentation ; *Confidentiality ; Humans ; Information Systems/*instrumentation ; Telemedicine/*instrumentation ; }, abstract = {Authentication and key agreement schemes play a very important role in enhancing the level of security of telecare medicine information systems (TMISs). Recently, Amin and Biswas demonstrated that the authentication scheme proposed by Giri et al. is vulnerable to off-line password guessing attacks and privileged insider attacks and also does not provide user anonymity. They also proposed an improved authentication scheme, claiming that it resists various security attacks. However, this paper demonstrates that Amin and Biswas's scheme is defenseless against off-line password guessing attacks and replay attacks and also does not provide perfect forward secrecy. This paper also shows that Giri et al.'s scheme not only suffers from the weaknesses pointed out by Amin and Biswas, but it also is vulnerable to replay attacks and does not provide perfect forward secrecy. Moreover, this paper proposes a novel authentication and key agreement scheme to overcome the mentioned weaknesses. Security and performance analyses show that the proposed scheme not only overcomes the mentioned security weaknesses, but also is more efficient than the previous schemes.}, } @article {pmid27659293, year = {2017}, author = {Brown, MF and Brown, AA}, title = {The promise of cyborg intelligence.}, journal = {Learning & behavior}, volume = {45}, number = {1}, pages = {5-6}, pmid = {27659293}, issn = {1543-4508}, mesh = {Algorithms ; Animals ; *Artificial Intelligence ; Choice Behavior ; Cognition ; *Intelligence ; Rats ; *Robotics ; }, abstract = {Yu et al. (2016) demonstrated that algorithms designed to find efficient routes in standard mazes can be integrated with the natural processes controlling rat navigation and spatial choices, and they pointed out the promise of such "cyborg intelligence" for biorobotic applications. Here, we briefly describe Yu et al.'s work, explore its relevance to the study of comparative cognition, and indicate how work involving cyborg intelligence would benefit from interdisciplinary collaboration between behavioral scientists and engineers.}, } @article {pmid27655011, year = {2016}, author = {Chu, T and Vyboishchikov, SF and Gabidullin, B and Nikonov, GI}, title = {Oxidative Cleavage of C=S and P=S Bonds at an Al[I] Center: Preparation of Terminally Bound Aluminum Sulfides.}, journal = {Angewandte Chemie (International ed. in English)}, volume = {55}, number = {42}, pages = {13306-13311}, doi = {10.1002/anie.201607735}, pmid = {27655011}, issn = {1521-3773}, abstract = {The treatment of cyclic thioureas with the aluminum(I) compound NacNacAl (1; NacNac=[ArNC(Me)CHC(Me)NAr][-] , Ar=2,6-Pr[i]2 C6 H3) resulted in oxidative cleavage of the C=S bond and the formation of 3 and 5, the first monomeric aluminum complexes with an Al=S double bond stabilized by N-heterocyclic carbenes. Compound 1 also reacted with triphenylphosphine sulfide in a similar manner, which resulted in cleavage of the P=S bond and production of the adduct [NacNacAl=S(S=PPh3)] (8). The Al=S double bond in 3 can react with phenyl isothiocyanate to furnish the cycloaddition product 9 and zwitterion 10 as a result of coupling between the liberated carbene and PhN=C=S. All novel complexes were characterized by multinuclear NMR spectroscopy, and the structures of 5, 9, and 10 were confirmed by X-ray diffraction analysis. The nature of the Al=S bond in 5 was also probed by DFT calculations.}, } @article {pmid27649829, year = {2016}, author = {Chambers, TS}, title = {Telos versus Praxis in Bioethics.}, journal = {The Hastings Center report}, volume = {46}, number = {5}, pages = {41-42}, doi = {10.1002/hast.617}, pmid = {27649829}, issn = {1552-146X}, mesh = {*Bioethics ; Dissent and Disputes ; *Fellowships and Scholarships ; Freedom ; Humans ; Male ; Research ; }, abstract = {The authors of "A Conceptual Model for the Translation of Bioethics Research and Scholarship" argue that bioethics must respond to institutional pressures by demonstrating that it is having an impact in the world. Any impact, the authors observe, must be "informed" by the goals of the discipline of bioethics. The concept of bioethics as a discipline is central to their argument. They begin by citing an essay that Daniel Callahan wrote in the first issue of Hastings Center Studies. Callahan argued in this 1973 piece that bioethics had yet to attain the status of a discipline, and he lauded the freedom of being able to define a new discipline. Callahan's essay shares with Mathews and colleague's a peculiarity: neither ever defines what it means to refer to something as a "discipline." To define a discipline does mean attending to the intended end product of scholarly activity, so I concur with Mathews et al.'s focus on outcomes. But I am concerned that in their argument they confusingly entangle their understanding of an academic discipline's internal goals, its telos, with its potential to have an impact on the external world, its praxis. The confusion that this can bring exposes what I believe is a profound problem within bioethics, the discipline's peculiar and at times intellectually hazardous relationship with its institutional hosts.}, } @article {pmid27646969, year = {2016}, author = {Chaudhry, SA and Khan, MT and Khan, MK and Shon, T}, title = {A Multiserver Biometric Authentication Scheme for TMIS using Elliptic Curve Cryptography.}, journal = {Journal of medical systems}, volume = {40}, number = {11}, pages = {230}, pmid = {27646969}, issn = {1573-689X}, mesh = {Biometric Identification/*instrumentation ; Computer Security/*instrumentation ; Confidentiality ; Health Information Exchange ; Health Smart Cards ; Humans ; Telemedicine/*instrumentation ; }, abstract = {Recently several authentication schemes are proposed for telecare medicine information system (TMIS). Many of such schemes are proved to have weaknesses against known attacks. Furthermore, numerous such schemes cannot be used in real time scenarios. Because they assume a single server for authentication across the globe. Very recently, Amin et al. (J. Med. Syst. 39(11):180, 2015) designed an authentication scheme for secure communication between a patient and a medical practitioner using a trusted central medical server. They claimed their scheme to extend all security requirements and emphasized the efficiency of their scheme. However, the analysis in this article proves that the scheme designed by Amin et al. is vulnerable to stolen smart card and stolen verifier attacks. Furthermore, their scheme is having scalability issues along with inefficient password change and password recovery phases. Then we propose an improved scheme. The proposed scheme is more practical, secure and lightweight than Amin et al.'s scheme. The security of proposed scheme is proved using the popular automated tool ProVerif.}, } @article {pmid27636006, year = {2016}, author = {Andrews, TJ and Baseler, H and Jenkins, R and Burton, AM and Young, AW}, title = {Contributions of feature shapes and surface cues to the recognition and neural representation of facial identity.}, journal = {Cortex; a journal devoted to the study of the nervous system and behavior}, volume = {83}, number = {}, pages = {280-291}, doi = {10.1016/j.cortex.2016.08.008}, pmid = {27636006}, issn = {1973-8102}, mesh = {Adolescent ; Adult ; Brain Mapping/methods ; Cues ; Female ; Humans ; Image Processing, Computer-Assisted ; Magnetic Resonance Imaging ; Male ; Occipital Lobe/diagnostic imaging/*physiology ; Photic Stimulation ; Recognition, Psychology/*physiology ; Temporal Lobe/diagnostic imaging/*physiology ; Young Adult ; }, abstract = {A full understanding of face recognition will involve identifying the visual information that is used to discriminate different identities and how this is represented in the brain. The aim of this study was to explore the importance of shape and surface properties in the recognition and neural representation of familiar faces. We used image morphing techniques to generate hybrid faces that mixed shape properties (more specifically, second order spatial configural information as defined by feature positions in the 2D-image) from one identity and surface properties from a different identity. Behavioural responses showed that recognition and matching of these hybrid faces was primarily based on their surface properties. These behavioural findings contrasted with neural responses recorded using a block design fMRI adaptation paradigm to test the sensitivity of Haxby et al.'s (2000) core face-selective regions in the human brain to the shape or surface properties of the face. The fusiform face area (FFA) and occipital face area (OFA) showed a lower response (adaptation) to repeated images of the same face (same shape, same surface) compared to different faces (different shapes, different surfaces). From the behavioural data indicating the critical contribution of surface properties to the recognition of identity, we predicted that brain regions responsible for familiar face recognition should continue to adapt to faces that vary in shape but not surface properties, but show a release from adaptation to faces that vary in surface properties but not shape. However, we found that the FFA and OFA showed an equivalent release from adaptation to changes in both shape and surface properties. The dissociation between the neural and perceptual responses suggests that, although they may play a role in the process, these core face regions are not solely responsible for the recognition of facial identity.}, } @article {pmid27628729, year = {2016}, author = {Xiong, H and Tao, J and Chen, Y}, title = {A Robust and Anonymous Two Factor Authentication and Key Agreement Protocol for Telecare Medicine Information Systems.}, journal = {Journal of medical systems}, volume = {40}, number = {11}, pages = {228}, pmid = {27628729}, issn = {1573-689X}, mesh = {Computer Security/*instrumentation ; Confidentiality ; Health Information Exchange/standards ; *Health Smart Cards ; Humans ; Information Systems/*instrumentation ; Nonlinear Dynamics ; Telemedicine/*instrumentation ; }, abstract = {Nowadays people can get many services including health-care services from distributed information systems remotely via public network. By considering that these systems are built on public network, they are vulnerable to many malicious attacks. Hence it is necessary to introduce an effective mechanism to protect both users and severs. Recently many two-factor authentication schemes have been proposed to achieve this goal. In 2016, Li et al. demonstrated that Lee et al.'s scheme was not satisfactory to be deployed in practice because of its security weaknesses and then proposed a security enhanced scheme to overcome these drawbacks. In this paper, we analyze Li et al.'s scheme is still not satisfactory to be applied in telecare medicine information systems (TMIS) because it fails to withstand off-line dictionary attack and known session-specific temporary information attack. Moreover, their scheme cannot provide card revocation services for lost smart card. In order to solve these security problems, we propose an improved scheme. Then we analyze our scheme by using BAN-logic model and compare the improved scheme with related schemes to prove that our scheme is advantageous to be applied in practice.}, } @article {pmid27625441, year = {2016}, author = {Mullerpattan, JB and Udwadia, ZZ and Kathar, SS and Shah, HD and Rastogi, SA and Pandey, KV and Udwadia, ZF}, title = {Who will teach the teachers: An analysis of the inhaler technique of Indian patients and health care providers in a tertiary health care centre.}, journal = {Lung India : official organ of Indian Chest Society}, volume = {33}, number = {5}, pages = {493-495}, pmid = {27625441}, issn = {0970-2113}, abstract = {INTRODUCTION: The proper use of inhalers is essential for ensuring proper control of the disease. Various studies have shown high levels of improper use and lack of knowledge of the correct technique among patients with asthma. However, less data are available on how health care workers (HCW's) use inhalers.

MATERIALS AND METHODS: The study was conducted at a Tertiary Care Hospital in Mumbai. We evaluated the pMDI technique in 141 consecutive adult asthmatics and 100 HCW's. All patients and HCW's were graded out of 10 points for following 10 steps. These were derived from Melani et al.'s study on inhaler mishandling.

RESULTS: Techniques of 141 patients and 100 HCW's (55 nurses and 45 doctors) were analyzed. The average technique score among patients ranged from 0 to 10 with a mean of 4.65 ± 2.00. The combined score for health workers ranged from 3 to 9 with a mean of 5.45 ± 1.47. Doctors had a higher score of 6.35 ± 1.33 as opposed to the nurses' score of 4.70 ± 1.13 (P < 0.05). There was no significant difference between scores of nurses and patients (P > 0.05).

CONCLUSIONS: Our study highlights the need for better education of not only patients but also health care providers regarding the appropriate use of inhaler devices in order to achieve optimal control of obstructive airway diseases.}, } @article {pmid27622165, year = {2016}, author = {Norozi, E and Miri, MR and Soltani, R and Eslami, AA and Harivandi, AR and Dastjerdi, R}, title = {Cultural Adaptation and Psychometric Properties of the Persian Version of the Circumstances, Motivation, and Readiness Scale.}, journal = {International journal of high risk behaviors & addiction}, volume = {5}, number = {2}, pages = {e23242}, pmid = {27622165}, issn = {2251-8711}, abstract = {BACKGROUND: Treatment motivation has always been an important issue in substance abuse treatment. In recent decades, several instruments have been developed to measure this concept.

OBJECTIVES: In this study, cultural adaptation and psychometric properties of the Persian version of the circumstances, motivation and readiness scale (CMR) are illustrated in a sample of Iranian addicts.

MATERIALS AND METHODS: The translation process followed Beaton et al.'s (2000) guideline for the cross-cultural adaptation of self-administered questionnaires, including the steps of translation, synthesis, back translation, expert committee review, and pre-testing. The final version of the Persian CMR was assessed for internal consistency and construct validity (n = 203).

RESULTS: There was one eliminated item in the cross-cultural adaptation process. Also, four items that had low correlation with the total score were excluded from the questionnaire during the initial analysis. Using the remaining items, Principle axis factoring with Promax rotation was performed and three factors, circumstance, motivation, and readiness, were identified. The secondary order three factor model provided a good statistical and conceptual fit for the data. Internal consistency met the criterion for a reliable measure (Cronbach's alpha = 0.840). The α range for these identified factors was 0.597 to 0.837.

CONCLUSIONS: Although the CMR was originally designed for use in TC treatment, this study suggests that it is also applicable, with some modifications, in short-term residential camps. Also, it is concluded that the Persian translation of the CMR can be applied for studies among Persian addicts.}, } @article {pmid27621271, year = {2016}, author = {Harris, DA}, title = {A Descriptive Model of Desistance From Sexual Offending: Examining the Narratives of Men Released From Custody.}, journal = {International journal of offender therapy and comparative criminology}, volume = {60}, number = {15}, pages = {1717-1737}, doi = {10.1177/0306624X16668176}, pmid = {27621271}, issn = {1552-6933}, abstract = {Despite an increasing interest in desistance from sexual offending, a comprehensive theoretical account of the process has yet to be provided. This study examines the narratives of 60 men interviewed in the community, who were incarcerated for sexual offenses and released. Recent findings from this research conclude that men desist from sexual offending, but they seldom follow the processes described by traditional criminology. In many cases, in fact, they desist in spite of their inability to pursue Sampson and Laub's "informal social controls" or Giordano et al.'s "hooks for change." The relentless impact of current public policies such as community notification and electronic monitoring further impedes their likelihood of experiencing Maruna's "Pygmalion effect" or achieving true cognitive transformation or agentic change. The descriptive model introduced here identifies four styles of desistance from sexual offending: "age," "resignation," "rote," and "resilience." Relevant implications are discussed.}, } @article {pmid27606051, year = {2016}, author = {Holcombe, AO and Brown, NJ and Goodbourn, PT and Etz, A and Geukes, S}, title = {Does sadness impair color perception? Flawed evidence and faulty methods.}, journal = {F1000Research}, volume = {5}, number = {}, pages = {1778}, pmid = {27606051}, issn = {2046-1402}, abstract = {In their 2015 paper, Thorstenson, Pazda, and Elliot offered evidence from two experiments that perception of colors on the blue-yellow axis was impaired if the participants had watched a sad movie clip, compared to participants who watched clips designed to induce a happy or neutral mood. Subsequently, these authors retracted their article, citing a mistake in their statistical analyses and a problem with the data in one of their experiments. Here, we discuss a number of other methodological problems with Thorstenson et al.'s experimental design, and also demonstrate that the problems with the data go beyond what these authors reported. We conclude that repeating one of the two experiments, with the minor revisions proposed by Thorstenson et al., will not be sufficient to address the problems with this work.}, } @article {pmid27602008, year = {2016}, author = {Loera, B and Martini, M and Viotti, S and Converso, D}, title = {Users' Support as a Social Resource in Educational Services: Construct Validity and Measurement Invariance of the User-Initiated Support Scale (UISS).}, journal = {Frontiers in psychology}, volume = {7}, number = {}, pages = {1248}, pmid = {27602008}, issn = {1664-1078}, abstract = {Social support is an important resource for reducing the risks of stress and burnout at work. It seems to be particularly helpful for educational and social professionals. The constant and intense relationships with users that characterize this kind of service can be very demanding, increasing stress and leading to burnout. While significant attention has been paid to supervisors and colleagues in the literature, users have rarely been considered as possible sources of social support. The only exception is the Zimmermann et al.'s (2011) research, focused on customer support as a resource for workers' well-being. This paper proposes the validation of the customer-initiated support scale developed by Zimmermann et al. (2011), translated into Italian and focused on educational services users (children's parents), to measure the user support perceived by workers: the User-Initiated Support Scale (UISS). In Study 1 (105 teachers), which specifically involved educators and kindergarten teachers, the items and scale properties were preliminarily examined using descriptive analyses and exploratory factor analysis (EFA). In Study 2 (304 teachers), the construct and criterion validity and scale dimensionality were analyzed using confirmatory factor analysis (CFA). In Study 3 (304 teachers from Study 2 and 296 educators), measurement invariance (MI) was tested. The EFA results from Study 1 showed a one-factor solution (explained variance, 67.2%). The scale showed good internal coherence (alpha = 0.88). The CFA in Study 2 validated the one-factor solution (comparative fit index = 0.987; standardized root mean square residual = 0.054). Bivariate correlations confirmed construct validity; the UISS was positively associated (convergent) with user gratitude, and not associated (divergent) with disproportionate customer expectations. Regarding the criterion validity test, the UISS was strongly correlated with burnout and job satisfaction. The analysis of MI performed on the Study 3 data confirmed the equality of the parameters of the covariance structure model between the two samples of kindergarten teachers and educators. This research study offers a useful version of a tool for measuring a crucial, but often ignored, protective resource for all professionals working directly with people (patients, students, and service users) that can represent important sources of well-being, directly or indirectly lessening the negative impacts of job demands.}, } @article {pmid27586489, year = {2016}, author = {Sutrala, AK and Das, AK and Odelu, V and Wazid, M and Kumari, S}, title = {Secure anonymity-preserving password-based user authentication and session key agreement scheme for telecare medicine information systems.}, journal = {Computer methods and programs in biomedicine}, volume = {135}, number = {}, pages = {167-185}, doi = {10.1016/j.cmpb.2016.07.028}, pmid = {27586489}, issn = {1872-7565}, mesh = {*Computer Security ; *Information Systems ; *Privacy ; *Telemedicine ; }, abstract = {BACKGROUND AND OBJECTIVES: Information and communication and technology (ICT) has changed the entire paradigm of society. ICT facilitates people to use medical services over the Internet, thereby reducing the travel cost, hospitalization cost and time to a greater extent. Recent advancements in Telecare Medicine Information System (TMIS) facilitate users/patients to access medical services over the Internet by gaining health monitoring facilities at home.

METHODS: Amin and Biswas recently proposed a RSA-based user authentication and session key agreement protocol usable for TMIS, which is an improvement over Giri et al.'s RSA-based user authentication scheme for TMIS. In this paper, we show that though Amin-Biswas's scheme considerably improves the security drawbacks of Giri et al.'s scheme, their scheme has security weaknesses as it suffers from attacks such as privileged insider attack, user impersonation attack, replay attack and also offline password guessing attack. A new RSA-based user authentication scheme for TMIS is proposed, which overcomes the security pitfalls of Amin-Biswas's scheme and also preserves user anonymity property.

RESULTS: The careful formal security analysis using the two widely accepted Burrows-Abadi-Needham (BAN) logic and the random oracle models is done. Moreover, the informal security analysis of the scheme is also done. These security analyses show the robustness of our new scheme against the various known attacks as well as attacks found in Amin-Biswas's scheme. The simulation of the proposed scheme using the widely accepted Automated Validation of Internet Security Protocols and Applications (AVISPA) tool is also done.

CONCLUSIONS: We present a new user authentication and session key agreement scheme for TMIS, which fixes the mentioned security pitfalls found in Amin-Biswas's scheme, and we also show that the proposed scheme provides better security than other existing schemes through the rigorous security analysis and verification tool. Furthermore, we present the formal security verification of our scheme using the widely accepted AVISPA tool. High security and extra functionality features allow our proposed scheme to be applicable for telecare medicine information systems which is used for e-health care medical applications.}, } @article {pmid27584725, year = {2016}, author = {Barrett, LF and Gendron, M}, title = {The importance of context: Three corrections to Cordaro, Keltner, Tshering, Wangchuk, and Flynn (2016).}, journal = {Emotion (Washington, D.C.)}, volume = {16}, number = {6}, pages = {803-806}, pmid = {27584725}, issn = {1931-1516}, support = {F32 MH105052/MH/NIMH NIH HHS/United States ; }, mesh = {Emotions/*physiology ; Humans ; Internationality ; Research Design ; }, abstract = {In their recently published article, "The Voice Conveys Emotion in Ten Globalized Cultures and One Remote Village in Bhutan," Cordaro, Keltner, Tshering, Wangchuk, and Flynn conclude that certain emotion categories are universally recognized by people around the world, barring illness and measurement error. The impact of Cordaro et al.'s article, like that of all empirical studies, is determined not only by its research findings but also by how the research findings are situated. Accuracy in characterizing the scientific context of new findings is as important as maintaining the highest standards for other aspects of the scientific method. In this regard, we point out three areas of concern in Cordaro et al.'s discussion of past research on remote samples, the use of more discovery-oriented (and less confirmatory) experimental methods in past research, and the use of manipulation checks in past research. Ultimately, a study's contribution to scientific progress is limited when ambiguities and oversights obscure the real value of its findings. (PsycINFO Database Record}, } @article {pmid27582323, year = {2016}, author = {Murata, I and Goto, M and Komiya, M and Motohashi, R and Hirata, M and Inoue, Y and Kanamoto, I}, title = {Early Therapeutic Intervention for Crush Syndrome: Characterization of Intramuscular Administration of Dexamethasone by Pharmacokinetic and Biochemical Parameters in Rats.}, journal = {Biological & pharmaceutical bulletin}, volume = {39}, number = {9}, pages = {1424-1431}, doi = {10.1248/bpb.b15-01034}, pmid = {27582323}, issn = {1347-5215}, mesh = {Animals ; Anti-Inflammatory Agents/administration & dosage/pharmacokinetics/pharmacology/*therapeutic use ; Arterial Pressure/drug effects ; Crush Syndrome/blood/*drug therapy/metabolism ; Dexamethasone/administration & dosage/pharmacokinetics/pharmacology/*therapeutic use ; Injections, Intravenous ; Interleukin-6/blood ; Lung/drug effects/metabolism ; Male ; Muscle, Skeletal/metabolism ; Peroxidase/metabolism ; Rats, Wistar ; Thiobarbituric Acid Reactive Substances/metabolism ; }, abstract = {Crush syndrome (CS) is the systemic manifestation of muscle cell damage resulting from pressure and crushing. It is associated with a high mortality rate, even when patients are treated with conventional therapy. We demonstrated the utility of intramuscular administration of dexamethasone (DEX) in disaster medical care by using a model of CS to characterize the pharmacokinetics and biochemical parameters. We compared intravenous (IV) and intramuscular (IM) injection. The IM sites were the right anterior limb (AL), bilateral hind limbs (bHL), and unilateral hind limb (uHL). DEX (5.0 mg/kg) was administered in sham-operated (sham, S-IV, S-AL, S-bHL, S-uHL groups) and CS rats (control, C-IV, C-AL, C-bHL, C-uHL groups). The survival rate in the IM groups was lower than that in the C-IV group. Survival was highest in the C-AL group, followed by the C-uHL and C-bHL groups. The blood DEX concentration of the C-AL group was similar to that in the C-IV group. The C-bHL and C-uHL groups had decreased blood DEX concentrations. Moreover, inhibition of inflammation was related to these changes. Administration of DEX to non-injured muscle, as well as IV administration, increased the survival rate by modulating shock and inflammatory mediators, consequently suppressing myeloperoxidase activity and subsequent systemic inflammation, resulting in a complete recovery of rats from lethal CS. These results demonstrate that injection DEX into the non-injured muscle is a potentially effective early therapeutic intervention for CS that could easily be used in transport to the hospital.}, } @article {pmid27565706, year = {2018}, author = {Baker, EA and Klipfel, KM and van Dulmen, MHM}, title = {Self-Control and Emotional and Verbal Aggression in Dating Relationships: A Dyadic Understanding.}, journal = {Journal of interpersonal violence}, volume = {33}, number = {22}, pages = {3551-3571}, doi = {10.1177/0886260516636067}, pmid = {27565706}, issn = {1552-6518}, mesh = {Adolescent ; Adult ; Aggression/*psychology ; Courtship/*psychology ; Female ; Humans ; Interpersonal Relations ; Intimate Partner Violence/*psychology ; Male ; *Self-Control ; Sexual Partners/psychology ; Surveys and Questionnaires ; Young Adult ; }, abstract = {Guided by the dynamic developmental systems perspective, this study extends past research by examining the association between self-control and emotional and verbal aggression (EVA) using a dyadic multi-method design. Guided by empirical research and the dynamic developmental systems perspective, we hypothesized that (a) there would be a negative association between one's own self-control and one's own perpetration of EVA and (b) there would also be a negative association between one's partner's self-control and one's own perpetration of EVA. One hundred twenty heterosexual dating couples (ages 18-25 years) provided data on self-control (Grasmick et al.'s Low Self-Control Scale; reverse scored for ease of interpretation), self-reported perpetration of EVA (Emotional and Verbal Abuse subscale of the Conflict in Adolescent Dating Relationships Inventory), and observationally assessed perpetration of EVA. Data were analyzed using path analyses within the Actor-Partner Interdependence Model (APIM) framework. Consistent with previous findings, we found that self-control was negatively associated with the perpetration of EVA. Furthermore, we found partner effects, such that female-but not male-self-control predicted partner-observed perpetration of EVA. These findings highlight the importance of examining risk factors for EVA of both partners. Our findings also suggest that the association between self-control and EVA is partially a function of whether EVA is assessed through self-report or observational methodology. This highlights the need to conduct multi-method assessments in future research. As discussed in the article, our findings have implications for theories on intimate partner violence, study designs, and couple interventions.}, } @article {pmid27559279, year = {2016}, author = {Apeldoorn, AT and van Helvoirt, H and Ostelo, RW and Meihuizen, H and Kamper, SJ and van Tulder, MW and de Vet, HC}, title = {Inter-rater reliability of a modified version of Delitto et al.'s classification-based system for low back pain: a pilot study.}, journal = {The Journal of manual & manipulative therapy}, volume = {24}, number = {2}, pages = {98-110}, pmid = {27559279}, issn = {1066-9817}, abstract = {STUDY DESIGN: Observational inter-rater reliability study.

OBJECTIVES: To examine: (1) the inter-rater reliability of a modified version of Delitto et al.'s classification-based algorithm for patients with low back pain; (2) the influence of different levels of familiarity with the system; and (3) the inter-rater reliability of algorithm decisions in patients who clearly fit into a subgroup (clear classifications) and those who do not (unclear classifications).

METHODS: Patients were examined twice on the same day by two of three participating physical therapists with different levels of familiarity with the system. Patients were classified into one of four classification groups. Raters were blind to the others' classification decision. In order to quantify the inter-rater reliability, percentages of agreement and Cohen's Kappa were calculated.

RESULTS: A total of 36 patients were included (clear classification n = 23; unclear classification n = 13). The overall rate of agreement was 53% and the Kappa value was 0·34 [95% confidence interval (CI): 0·11-0·57], which indicated only fair inter-rater reliability. Inter-rater reliability for patients with a clear classification (agreement 52%, Kappa value 0·29) was not higher than for patients with an unclear classification (agreement 54%, Kappa value 0·33). Familiarity with the system (i.e. trained with written instructions and previous research experience with the algorithm) did not improve the inter-rater reliability.

CONCLUSION: Our pilot study challenges the inter-rater reliability of the classification procedure in clinical practice. Therefore, more knowledge is needed about factors that affect the inter-rater reliability, in order to improve the clinical applicability of the classification scheme.}, } @article {pmid27537890, year = {2016}, author = {Jung, J and Kim, J and Choi, Y and Won, D}, title = {An Anonymous User Authentication and Key Agreement Scheme Based on a Symmetric Cryptosystem in Wireless Sensor Networks.}, journal = {Sensors (Basel, Switzerland)}, volume = {16}, number = {8}, pages = {}, pmid = {27537890}, issn = {1424-8220}, abstract = {In wireless sensor networks (WSNs), a registered user can login to the network and use a user authentication protocol to access data collected from the sensor nodes. Since WSNs are typically deployed in unattended environments and sensor nodes have limited resources, many researchers have made considerable efforts to design a secure and efficient user authentication process. Recently, Chen et al. proposed a secure user authentication scheme using symmetric key techniques for WSNs. They claim that their scheme assures high efficiency and security against different types of attacks. After careful analysis, however, we find that Chen et al.'s scheme is still vulnerable to smart card loss attack and is susceptible to denial of service attack, since it is invalid for verification to simply compare an entered ID and a stored ID in smart card. In addition, we also observe that their scheme cannot preserve user anonymity. Furthermore, their scheme cannot quickly detect an incorrect password during login phase, and this flaw wastes both communication and computational overheads. In this paper, we describe how these attacks work, and propose an enhanced anonymous user authentication and key agreement scheme based on a symmetric cryptosystem in WSNs to address all of the aforementioned vulnerabilities in Chen et al.'s scheme. Our analysis shows that the proposed scheme improves the level of security, and is also more efficient relative to other related schemes.}, } @article {pmid27535161, year = {2016}, author = {Talaat, W and Ghoneim, MM and Elsholkamy, M}, title = {Dr. Wael Talaat et al.'s reply.}, journal = {Cranio : the journal of craniomandibular practice}, volume = {34}, number = {5}, pages = {352}, doi = {10.1080/08869634.2016.1211832}, pmid = {27535161}, issn = {2151-0903}, } @article {pmid27515846, year = {2016}, author = {de Vries, YA and Roest, AM and Franzen, M and Munafò, MR and Bastiaansen, JA}, title = {Citation bias and selective focus on positive findings in the literature on the serotonin transporter gene (5-HTTLPR), life stress and depression.}, journal = {Psychological medicine}, volume = {46}, number = {14}, pages = {2971-2979}, doi = {10.1017/S0033291716000805}, pmid = {27515846}, issn = {1469-8978}, support = {//British Heart Foundation/United Kingdom ; //Cancer Research UK/United Kingdom ; //Medical Research Council/United Kingdom ; //Department of Health/United Kingdom ; }, mesh = {*Bibliometrics ; *Depressive Disorder, Major/etiology/genetics ; Humans ; Publication Bias/*statistics & numerical data ; Serotonin Plasma Membrane Transport Proteins/*physiology ; *Stress, Psychological/complications ; }, abstract = {BACKGROUND: Caspi et al.'s 2003 report that 5-HTTLPR genotype moderates the influence of life stress on depression has been highly influential but remains contentious. We examined whether the evidence base for the 5-HTTLPR-stress interaction has been distorted by citation bias and a selective focus on positive findings.

METHOD: A total of 73 primary studies were coded for study outcomes and focus on positive findings in the abstract. Citation rates were compared between studies with positive and negative results, both within this network of primary studies and in Web of Science. In addition, the impact of focus on citation rates was examined.

RESULTS: In all, 24 (33%) studies were coded as positive, but these received 48% of within-network and 68% of Web of Science citations. The 38 (52%) negative studies received 42 and 23% of citations, respectively, while the 11 (15%) unclear studies received 10 and 9%. Of the negative studies, the 16 studies without a positive focus (42%) received 47% of within-network citations and 32% of Web of Science citations, while the 13 (34%) studies with a positive focus received 39 and 51%, respectively, and the nine (24%) studies with a partially positive focus received 14 and 17%.

CONCLUSIONS: Negative studies received fewer citations than positive studies. Furthermore, over half of the negative studies had a (partially) positive focus, and Web of Science citation rates were higher for these studies. Thus, discussion of the 5-HTTLPR-stress interaction is more positive than warranted. This study exemplifies how evidence-base-distorting mechanisms undermine the authenticity of research findings.}, } @article {pmid27515308, year = {2016}, author = {Camilleri, ET and Gustafson, MP and Dudakovic, A and Riester, SM and Garces, CG and Paradise, CR and Takai, H and Karperien, M and Cool, S and Sampen, HJ and Larson, AN and Qu, W and Smith, J and Dietz, AB and van Wijnen, AJ}, title = {Identification and validation of multiple cell surface markers of clinical-grade adipose-derived mesenchymal stromal cells as novel release criteria for good manufacturing practice-compliant production.}, journal = {Stem cell research & therapy}, volume = {7}, number = {1}, pages = {107}, pmid = {27515308}, issn = {1757-6512}, support = {F32 AR066508/AR/NIAMS NIH HHS/United States ; R01 AR049069/AR/NIAMS NIH HHS/United States ; }, mesh = {Adipose Tissue/cytology/*metabolism ; Adiposity/physiology ; Biomarkers/*metabolism ; Bone Marrow Cells/cytology/metabolism ; Cell Proliferation/physiology ; Cells, Cultured ; Flow Cytometry/methods ; Humans ; Mesenchymal Stem Cells/cytology/*metabolism ; Sequence Analysis, RNA/methods ; Transcriptome/physiology ; }, abstract = {BACKGROUND: Clinical translation of mesenchymal stromal cells (MSCs) necessitates basic characterization of the cell product since variability in biological source and processing of MSCs may impact therapeutic outcomes. Although expression of classical cell surface markers (e.g., CD90, CD73, CD105, and CD44) is used to define MSCs, identification of functionally relevant cell surface markers would provide more robust release criteria and options for quality control. In addition, cell surface expression may distinguish between MSCs from different sources, including bone marrow-derived MSCs and clinical-grade adipose-derived MSCs (AMSCs) grown in human platelet lysate (hPL).

METHODS: In this work we utilized quantitative PCR, flow cytometry, and RNA-sequencing to characterize AMSCs grown in hPL and validated non-classical markers in 15 clinical-grade donors.

RESULTS: We characterized the surface marker transcriptome of AMSCs, validated the expression of classical markers, and identified nine non-classical markers (i.e., CD36, CD163, CD271, CD200, CD273, CD274, CD146, CD248, and CD140B) that may potentially discriminate AMSCs from other cell types. More importantly, these markers exhibit variability in cell surface expression among different cell isolates from a diverse cohort of donors, including freshly prepared, previously frozen, or proliferative state AMSCs and may be informative when manufacturing cells.

CONCLUSIONS: Our study establishes that clinical-grade AMSCs expanded in hPL represent a homogeneous cell culture population according to classical markers,. Additionally, we validated new biomarkers for further AMSC characterization that may provide novel information guiding the development of new release criteria.

CLINICAL TRIALS: Use of Autologous Bone Marrow Aspirate Concentrate in Painful Knee Osteoarthritis (BMAC): Clinicaltrials.gov NCT01931007 . Registered August 26, 2013. MSC for Occlusive Disease of the Kidney: Clinicaltrials.gov NCT01840540 . Registered April 23, 2013. Mesenchymal Stem Cell Therapy in Multiple System Atrophy: Clinicaltrials.gov NCT02315027 . Registered October 31, 2014. Efficacy and Safety of Adult Human Mesenchymal Stem Cells to Treat Steroid Refractory Acute Graft Versus Host Disease. Clinicaltrials.gov NCT00366145 . Registered August 17, 2006. A Dose-escalation Safety Trial for Intrathecal Autologous Mesenchymal Stem Cell Therapy in Amyotrophic Lateral Sclerosis. Clinicaltrials.gov NCT01609283 . Registered May 18, 2012.}, } @article {pmid27501369, year = {2016}, author = {Shou, Y and Sellbom, M and Han, J}, title = {Development and Validation of the Chinese Triarchic Psychopathy Measure.}, journal = {Journal of personality disorders}, volume = {30}, number = {4}, pages = {436-450}, doi = {10.1521/pedi.2016.30.4.436}, pmid = {27501369}, issn = {1943-2763}, mesh = {Antisocial Personality Disorder/*diagnosis/psychology ; Asian People ; China ; Female ; Humans ; *Language ; Male ; Personality Inventory/*statistics & numerical data ; *Psychiatric Status Rating Scales ; Psychometrics ; Reproducibility of Results ; Self Report ; Students/psychology ; *Surveys and Questionnaires ; *Translations ; }, abstract = {The nature of psychopathy is not well understood in East Asian cultures, partially due to a lack of an established measurement of this important construct. This study developed and validated a Chinese-language version of the Triarchic Psychopathy Measure (TriPM) based on Patrick et al.'s (2009) triarchic model of psychopathy. Study 1 described the translation of the Chinese TriPM and demonstrated that the Chinese version of the TriPM is equivalent to the original English version in linguistic meaning. Study 2 examined the construct validity of the Chinese TriPM in a Chinese student sample. The TriPM evinced acceptable reliability and promising validity. Moreover, cross-cultural equivalence was examined by relative associations for the TriPM with the Levenson Self-Report Psychopathy Scale across the Chinese sample and a comparable United States student sample. Results revealed that the test bias in the strength of associations, regression intercepts, and slopes was mostly absent across the two samples.}, } @article {pmid27496781, year = {2017}, author = {Chen, LC and Chen, MH}, title = {Reply to Laganà et al.'s comment on "Risk of developing major depression and anxiety disorders among women with endometriosis: A longitudinal follow-up study".}, journal = {Journal of affective disorders}, volume = {208}, number = {}, pages = {674}, doi = {10.1016/j.jad.2016.07.047}, pmid = {27496781}, issn = {1573-2517}, mesh = {Anxiety ; Anxiety Disorders ; Depression ; *Depressive Disorder, Major ; *Endometriosis ; Female ; Follow-Up Studies ; Humans ; Longitudinal Studies ; }, } @article {pmid27496590, year = {2017}, author = {Manning, C and Kilner, J and Neil, L and Karaminis, T and Pellicano, E}, title = {Children on the autism spectrum update their behaviour in response to a volatile environment.}, journal = {Developmental science}, volume = {20}, number = {5}, pages = {}, pmid = {27496590}, issn = {1467-7687}, support = {MR/J013145/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Adolescent ; Adult ; Analysis of Variance ; Association Learning ; Autistic Disorder/*physiopathology/*psychology ; Case-Control Studies ; Child ; Choice Behavior/physiology ; *Environment ; Female ; Humans ; Learning ; Male ; Probability Learning ; Recognition, Psychology/physiology ; Reward ; *Social Behavior ; }, abstract = {Typical adults can track reward probabilities across trials to estimate the volatility of the environment and use this information to modify their learning rate (Behrens et al., 2007). In a stable environment, it is advantageous to take account of outcomes over many trials, whereas in a volatile environment, recent experience should be more strongly weighted than distant experience. Recent predictive coding accounts of autism propose that autistic individuals will demonstrate atypical updating of their behaviour in response to the statistics of the reward environment. To rigorously test this hypothesis, we administered a developmentally appropriate version of Behrens et al.'s (2007) task to 34 cognitively able children on the autism spectrum aged between 6 and 14 years, 32 age- and ability-matched typically developing children and 19 typical adults. Participants were required to choose between a green and a blue pirate chest, each associated with a randomly determined reward value between 0 and 100 points, with a combined total of 100 points. On each trial, the reward was given for one stimulus only. In the stable condition, the ratio of the blue or green response being rewarded was fixed at 75:25. In the volatile condition, the ratio alternated between 80:20 and 20:80 every 20 trials. We estimated the learning rate for each participant by fitting a delta rule model and compared this rate across conditions and groups. All groups increased their learning rate in the volatile condition compared to the stable condition. Unexpectedly, there was no effect of group and no interaction between group and condition. Thus, autistic children used information about the statistics of the reward environment to guide their decisions to a similar extent as typically developing children and adults. These results help constrain predictive coding accounts of autism by demonstrating that autism is not characterized by uniform differences in the weighting of prediction error.}, } @article {pmid27495862, year = {2016}, author = {Wetzler, MJ}, title = {Editorial Commentary: Pitching Should Come With a Warning Label.}, journal = {Arthroscopy : the journal of arthroscopic & related surgery : official publication of the Arthroscopy Association of North America and the International Arthroscopy Association}, volume = {32}, number = {8}, pages = {1569-1570}, doi = {10.1016/j.arthro.2016.06.001}, pmid = {27495862}, issn = {1526-3231}, mesh = {Academies and Institutes ; Baseball/*injuries ; *Biomechanical Phenomena ; Humans ; }, abstract = {Pitching is not without risk of overuse injuries. Pitch counts have been instituted to reduce the risk, but Riff et al.'s article clearly demonstrates that as pitchers get older they do not adhere to these counts, which increases the risk of injury.}, } @article {pmid27490104, year = {2016}, author = {Fredrickson, BL}, title = {Selective Data Analysis in Brown et al.'s Continued Critical Reanalysis.}, journal = {PloS one}, volume = {11}, number = {8}, pages = {e0160565}, pmid = {27490104}, issn = {1932-6203}, support = {R01 NR012899/NR/NINR NIH HHS/United States ; R01NR012899/JT/NIH HHS/United States ; }, mesh = {*Gene Expression Regulation ; Genomics/*methods ; Humans ; Linear Models ; Stress, Psychological/*genetics ; }, } @article {pmid27461109, year = {2016}, author = {Chan, AH and Hoffmann, ER}, title = {The Psychological Cost of Making Control Responses in the Nonstereotype Direction.}, journal = {Human factors}, volume = {58}, number = {8}, pages = {1173-1186}, doi = {10.1177/0018720816659000}, pmid = {27461109}, issn = {1547-8181}, mesh = {Adult ; *Data Display ; Humans ; *Man-Machine Systems ; *Models, Psychological ; *Task Performance and Analysis ; }, abstract = {OBJECTIVE: The aim of this study was to develop a scale for the "psychological cost" of making control responses in the nonstereotype direction.

BACKGROUND: Wickens, Keller, and Small suggested values for the psychological cost arising from having control/display relationships that were not in the common stereotype directions. We provide values of such costs specifically for these situations.

METHOD: Working from data of Chan and Hoffmann for 168 combinations of display location, control type, and display movement direction, we define values for the cost and compare these with the suggested values of Wickens et al.'s Frame of Reference Transformation Tool (FORT) model.

RESULTS: We found marked differences between the values of the FORT model and the data of our experiments. The differences arise largely from the effects of the Worringham and Beringer visual field principle not being adequately considered in the previous research.

CONCLUSION: A better indication of the psychological cost for use of incorrect control/display stereotypes is given. It is noted that these costs are applicable only to the factor of stereotype strength and not other factors considered in the FORT model.

APPLICATION: Effects of having controls and displays that are not arranged to operate with population expectancies can be readily determined from the data in this paper.}, } @article {pmid27458424, year = {2016}, author = {García-Pérez, MA and Alcalá-Quintana, R}, title = {The Interpretation of Scholars' Interpretations of Confidence Intervals: Criticism, Replication, and Extension of Hoekstra et al. (2014).}, journal = {Frontiers in psychology}, volume = {7}, number = {}, pages = {1042}, pmid = {27458424}, issn = {1664-1078}, abstract = {Hoekstra et al. (Psychonomic Bulletin & Review, 2014, 21:1157-1164) surveyed the interpretation of confidence intervals (CIs) by first-year students, master students, and researchers with six items expressing misinterpretations of CIs. They asked respondents to answer all items, computed the number of items endorsed, and concluded that misinterpretation of CIs is robust across groups. Their design may have produced this outcome artifactually for reasons that we describe. This paper discusses first the two interpretations of CIs and, hence, why misinterpretation cannot be inferred from endorsement of some of the items. Next, a re-analysis of Hoekstra et al.'s data reveals some puzzling differences between first-year and master students that demand further investigation. For that purpose, we designed a replication study with an extended questionnaire including two additional items that express correct interpretations of CIs (to compare endorsement of correct vs. nominally incorrect interpretations) and we asked master students to indicate which items they would have omitted had they had the option (to distinguish deliberate from uninformed endorsement caused by the forced-response format). Results showed that incognizant first-year students endorsed correct and nominally incorrect items identically, revealing that the two item types are not differentially attractive superficially; in contrast, master students were distinctively more prone to endorsing correct items when their uninformed responses were removed, although they admitted to nescience more often that might have been expected. Implications for teaching practices are discussed.}, } @article {pmid27449052, year = {2018}, author = {Stoeber, J}, title = {Comparing Two Short Forms of the Hewitt-Flett Multidimensional Perfectionism Scale.}, journal = {Assessment}, volume = {25}, number = {5}, pages = {578-588}, doi = {10.1177/1073191116659740}, pmid = {27449052}, issn = {1552-3489}, mesh = {Goals ; Humans ; Manifest Anxiety Scale ; Orientation ; *Perfectionism ; Psychometrics/*methods ; }, abstract = {Hewitt and Flett's 45-item Multidimensional Perfectionism Scale is a widely used instrument to assess self-oriented, other-oriented, and socially prescribed perfectionism. With 45 items, it is not overly lengthy, but there are situations where a short form is useful. Analyzing data from four samples, this article compares two frequently used 15-item short forms of the Multidimensional Perfectionism Scale-Cox et al.'s and Hewitt et al.'s-by examining to what degree their scores replicate the original version's correlations with various personality characteristics (e.g., traits, social goals, personal/interpersonal orientations). Regarding self-oriented and socially prescribed perfectionism, both short forms performed well. Regarding other-oriented perfectionism, however, Cox et al.'s short form (exclusively composed of negatively worded items) performed less well than Hewitt et al.'s (which contains no negatively worded items). It is recommended that researchers use Hewitt et al.'s short form to assess other-oriented perfectionism rather than Cox et al.'s.}, } @article {pmid27448517, year = {2016}, author = {Novo, AM and Batista, S and Tenente, J and Nunes, C and Macário, C and Sousa, L and Gonçalves, F}, title = {Apathy in multiple sclerosis: gender matters.}, journal = {Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia}, volume = {33}, number = {}, pages = {100-104}, doi = {10.1016/j.jocn.2016.02.038}, pmid = {27448517}, issn = {1532-2653}, mesh = {Adult ; Aged ; *Apathy ; Case-Control Studies ; Cognition Disorders/etiology/psychology ; Depression/psychology ; Educational Status ; Fatigue/psychology ; Female ; Humans ; Male ; Middle Aged ; Multiple Sclerosis/complications/epidemiology/*psychology ; Neuropsychological Tests ; Predictive Value of Tests ; Prevalence ; Psychiatric Status Rating Scales ; Sex Factors ; }, abstract = {Apathy has been recognized as a frequent symptom in multiple sclerosis (MS) but uncertainty remains about its prevalence and clinical correlates. Therefore, the objective of this work was to assess the prevalence of apathy in patients with MS and to identify clinical and demographic correlates. A case-control study with 30 patients and 30 healthy controls matched for age, gender and education was performed. Apathy diagnosis was established using Robert et al.'s criteria. Additionally, apathy was assessed using the 10-item short version of the clinical-rated Apathy Evaluation Scale (AES-C-10). The Beck Depression Inventory (BDI), Modified Fatigue Impact Scale (MFIS), and Montreal Cognitive Assessment (MoCA) were used to evaluate depression, fatigue and cognitive impairment, respectively. Apathy prevalence in MS patients was 43.3%. Patients with MS had higher AES-C-10 scores than controls (13.9 vs. 12.0, p=0.015). Patients with apathy presented a higher proportion of males (53.8% vs. 11.8%, p=0.02), lower educational level (53.8% vs. 11.8% of patients with up to 9years of education), higher scores on cognitive dimension of MFIS (18.0 vs. 8.0, p=0.048) and BDI (13.0 vs. 7.0, p=0.035) and worse performance on MoCA (24.0 vs. 26.0, p=0.028). Gender was the only independent predictor of apathy, with men presenting a higher risk compared to women (OR: 9.62; 95%CI: 1.02-90.61; p=0.048). In conclusion, apathy is a common neuropsychiatric disorder in MS and it is probably underdiagnosed. Male patients seem to have an increased risk of apathy, and this finding may be related to the generally more unfavorable course of MS in men.}, } @article {pmid27424171, year = {2016}, author = {Lessard, S and Bareil, C and Lalonde, L and Duhamel, F and Hudon, E and Goudreau, J and Lévesque, L}, title = {External facilitators and interprofessional facilitation teams: a qualitative study of their roles in supporting practice change.}, journal = {Implementation science : IS}, volume = {11}, number = {}, pages = {97}, pmid = {27424171}, issn = {1748-5908}, mesh = {Focus Groups ; *Health Personnel ; Health Plan Implementation/methods ; Humans ; *Interprofessional Relations ; *Organizational Innovation ; *Patient Care Team ; *Professional Role ; Qualitative Research ; }, abstract = {BACKGROUND: Facilitation is a powerful approach to support practice change. The purpose of this study is to better understand the facilitation roles exercised by both external facilitators and interprofessional facilitation teams to foster the implementation of change. Building on Dogherty et al.'s taxonomy of facilitation activities, this study uses an organizational development lens to identify and analyze facilitation roles. It includes a concise definition of what interprofessional facilitation teams actually do, thus expanding our limited knowledge of teams that act as change agents. We also investigate the facilitation dynamics between change actors.

METHODS: We carried out a qualitative analysis of a 1-year process of practice change implementation. We studied four family medicine groups, in which we constituted interprofessional facilitation teams. Each team was supported by one external facilitator and included at least one family physician, one case manager nurse, and health professionals located on or off the family medicine group's site (one pharmacist, plus at least one nutritionist, kinesiologist, or psychologist). We collected our data through focus group interviews with the four teams, individual interviews with the two external facilitators, and case audit documentation. We analyzed both predetermined (as per Dogherty et al., 2012) and emerging facilitation roles, as well as facilitation dynamics.

RESULTS: A non-linear framework of facilitation roles emerged from our data, based on four fields of expertise: change management, project management, meeting management, and group/interpersonal dynamics. We identified 72 facilitation roles, grouped into two categories: "implementation-oriented" and "support-oriented." Each category was subdivided into themes (n = 6; n = 5) for clearer understanding (e.g., legitimation of change/project, management of effective meetings). Finally, an examination of facilitation dynamics revealed eight relational ties occurring within and/or between groups of actors.

CONCLUSIONS: Facilitation is an approach used by appointed individuals, which teams can also foster, to build capacity and support practice change. Increased understanding of facilitation roles constitutes an asset in training practitioners such as organizational development experts, consultants, facilitators, and facilitation teams. It also helps decision makers become aware of the multiple roles and dynamics involved and the key competencies needed to recruit facilitators and members of interprofessional facilitation teams.}, } @article {pmid27412726, year = {2017}, author = {Custers, JA and Gielissen, MF and de Wilt, JH and Honkoop, A and Smilde, TJ and van Spronsen, DJ and van der Veld, W and van der Graaf, WT and Prins, JB}, title = {Towards an evidence-based model of fear of cancer recurrence for breast cancer survivors.}, journal = {Journal of cancer survivorship : research and practice}, volume = {11}, number = {1}, pages = {41-47}, pmid = {27412726}, issn = {1932-2267}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/mortality/*psychology ; Fear/*psychology ; Female ; Humans ; Middle Aged ; Neoplasm Recurrence, Local/*psychology ; Surveys and Questionnaires ; Survivors/*psychology ; }, abstract = {PURPOSE: In order to understand the multidimensional mechanism of fear of cancer recurrence (FCR) and to identify potential targets for interventions, it is important to empirically test the theoretical model of FCR. This study aims at assessing the validity of Lee-Jones et al.'s FCR model.

METHODS: A total of 1205 breast cancer survivors were invited to participate in this study. Participants received a questionnaire booklet including questionnaires on demographics and psychosocial variables including FCR. Data analysis consisted of the estimation of direct and indirect effects in mediator models.

RESULTS: A total of 460 women (38 %) participated in the study. Median age was 55.8 years (range 32-87). Indirect effects of external and internal cues via FCR were found for all mediation models with limited planning for the future (R [2] = .28) and body checking (R [2] = .11-.15) as behavioral response variables, with the largest effects for limited planning for the future. A direct relation was found between feeling sick and seeking professional advice, not mediated by FCR.

CONCLUSIONS: In the first tested models of FCR, all internal and external cues were associated with higher FCR. In the models with limited planning for the future and body checking as behavioral response, an indirect effect of cues via FCR was found supporting the theoretical model of Lee-Jones et al.

An evidence-based model of FCR may facilitate the development of appropriate interventions to manage FCR in breast cancer survivors.}, } @article {pmid27405258, year = {2017}, author = {Parra, MA}, title = {A commentary on Liang et al.'s paper with regard to emerging views of memory assessment in Alzheimer's disease.}, journal = {Cortex; a journal devoted to the study of the nervous system and behavior}, volume = {88}, number = {}, pages = {198-200}, doi = {10.1016/j.cortex.2016.06.006}, pmid = {27405258}, issn = {1973-8102}, support = {MR/K026992/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {*Alzheimer Disease ; Cognition ; Humans ; Memory Disorders ; *Neuropsychological Tests ; }, } @article {pmid27396467, year = {2016}, author = {Babor, TF and Miller, PR and Robaina, K}, title = {Reply to Cottler et al.'s Letter to the Editor.}, journal = {Addiction (Abingdon, England)}, volume = {111}, number = {8}, pages = {1489}, doi = {10.1111/add.13475}, pmid = {27396467}, issn = {1360-0443}, mesh = {*Conflict of Interest ; *Gambling ; Humans ; }, } @article {pmid27391959, year = {2016}, author = {Pérez, D and Van der Stuyft, P and Zabala, MC and Castro, M and Lefèvre, P}, title = {A modified theoretical framework to assess implementation fidelity of adaptive public health interventions.}, journal = {Implementation science : IS}, volume = {11}, number = {1}, pages = {91}, pmid = {27391959}, issn = {1748-5908}, mesh = {Cuba ; Dengue/*prevention & control ; Health Promotion/*methods ; Humans ; *Power, Psychological ; Program Evaluation/*methods ; Public Health/*methods ; }, abstract = {BACKGROUND: One of the major debates in implementation research turns around fidelity and adaptation. Fidelity is the degree to which an intervention is implemented as intended by its developers. It is meant to ensure that the intervention maintains its intended effects. Adaptation is the process of implementers or users bringing changes to the original design of an intervention. Depending on the nature of the modifications brought, adaptation could either be potentially positive or could carry the risk of threatening the theoretical basis of the intervention, resulting in a negative effect on expected outcomes. Adaptive interventions are those for which adaptation is allowed or even encouraged. Classical fidelity dimensions and conceptual frameworks do not address the issue of how to adapt an intervention while still maintaining its effectiveness.

DISCUSSION: We support the idea that fidelity and adaptation co-exist and that adaptations can impact either positively or negatively on the intervention's effectiveness. For adaptive interventions, research should answer the question how an adequate fidelity-adaptation balance can be reached. One way to address this issue is by looking systematically at the aspects of an intervention that are being adapted. We conducted fidelity research on the implementation of an empowerment strategy for dengue prevention in Cuba. In view of the adaptive nature of the strategy, we anticipated that the classical fidelity dimensions would be of limited use for assessing adaptations. The typology we used in the assessment-implemented, not-implemented, modified, or added components of the strategy-also had limitations. It did not allow us to answer the question which of the modifications introduced in the strategy contributed to or distracted from outcomes. We confronted our empirical research with existing literature on fidelity, and as a result, considered that the framework for implementation fidelity proposed by Carroll et al. in 2007 could potentially meet our concerns. We propose modifications to the framework to assess both fidelity and adaptation. The modified Carroll et al.'s framework we propose may permit a comprehensive assessment of the implementation fidelity-adaptation balance required when implementing adaptive interventions, but more empirical research is needed to validate it.}, } @article {pmid27389407, year = {2016}, author = {Yukun, L and Ke, G and Jiaming, S}, title = {Application of Nipple Retractor for Correction of Nipple Inversion: A 10-Year Experience.}, journal = {Aesthetic plastic surgery}, volume = {40}, number = {5}, pages = {707-715}, doi = {10.1007/s00266-016-0675-0}, pmid = {27389407}, issn = {1432-5241}, mesh = {Adolescent ; Adult ; Breast Diseases/diagnosis/*surgery ; Cohort Studies ; Equipment Design ; Female ; Follow-Up Studies ; Humans ; Nipples/*abnormalities/*surgery ; Plastic Surgery Procedures/*instrumentation/methods ; Retrospective Studies ; Surgical Flaps/*transplantation ; Surgical Instruments ; Treatment Outcome ; Wound Healing/physiology ; Young Adult ; }, abstract = {BACKGROUND: Nipple inversion is a relatively common problem in adolescent and adult women; however, most present surgical treatments are prone to injure the lactiferous ducts and impair the breast feeding function. A nipple retractor was developed by us in 2003 to correct nipple inversion to avoid lactiferous duct injury. The details and a 10-year evaluation of this technique were introduced in this paper.

METHODS: The nipple retractor was made from the hollow end of single-use syringe, then eight holes were punctured for sutures crossing the base, and the height of retractor depended on the sizes of nipple-areola complex and breast volume. Two sutures were made to cross beneath the base of the nipple to elevate the nipple, and the hollow retractor was placed on the areola with the nipple and four ends of the sutures in the center, sutures then passed the prefabricated holes on the retractor base and were fixed with knots and suitable tension. The retractor was worn for 3-6 months and then could be removed.

RESULTS: A total of 257 nipples in 136 patients with nipple inversion (unilateral: 15 patients; bilateral: 121 patients) received this operation from Jan 2003 to Dec 2012, among which 233 nipples were successfully corrected (90.7 %), and 24 nipples reoccurred in 2 years. The effective rates of grade I and grade II inversions were significantly higher than that of grade III (P < 0.01). Thirty-two patients with 56 treated nipples underwent labor and breastfeeding, and all the nipples were functional. The complications included fistula after suture removal (19 nipples, 7.4 %), breaking of suture (8 nipples, 3.1 %), erosion of nipple (28 nipples, 10.9 %), and chronic pain (10 nipples, 3.4 %), and all these complications were properly managed.

CONCLUSION: The nipple retractor technique is a feasible, effective, and safe method for correction of grade I and grade II nipple inversions, and could also be indicated for primary correction of grade III inversion. Its most significant advantage is that lactiferous duct injury can be avoided and the breast feeding function preserved.

LEVEL OF EVIDENCE V: Nipple inversion is a common malformation in adolescent and adult women, which can be present unilaterally or bilaterally. It was generally initiated from the adolescent period and could be caused by primary hypogenesis of smooth muscle and supporting tissue of the nipple-areola complex or hypoplasia of lactiferous ducts [1] . Some other secondary factors such as chronic infection, tumor, and previous surgery could contribute to the fibrosis, and some of them were believed to be congenital and hereditary [2, 3]. Since the openings of lactiferous ducts are immersed, inversion might cause reoccurring infection and breast feeding difficulty, and the appearance of the breast would be affected as well, which would impact patients' psychological health. Nipple inversion can be clinically divided into three categories according to Han et al.'s grading rules. In grade I, the nipple is easily pulled out manually and maintains its projection quite well. In grade II, the nipples can be pulled out but cannot maintain projection and tend to go back again. In grade III, the nipple can hardly be pulled out manually. [4] The images of three grades of nipple inversion are present in Fig. 1. Fig. 1 Three categories of nipple inversion grade I inverted nipple(a), grade II inverted nipple(b), grade III inverted nipple(c) Surgical interventions are the most effective treatments at present; however, injury to lactiferous ducts is inevitable in most surgical techniques [1, 5-10]. Some conservative nonoperative techniques have been developed in the last several years, such as a self-retraction and suction device, but only mild cases of grade I are indicated. Several suspension and retraction devices have been reported in recent years [10, 11], and the effect was acceptable, but long-term results were not reported. To simplify the operation procedures and diminish the possibility of lactiferous duct injury, we developed a nipple retractor, which was made from a single-use syringe, to correct nipple inversion from 2003. The details of procedures and techniques are introduced in this paper, as well as a 10-year retrospective analysis.}, } @article {pmid27386879, year = {2017}, author = {Romero-Sánchez, M and Carretero-Dios, H and Megías, JL and Moya, M and Ford, TE}, title = {Sexist Humor and Rape Proclivity: The Moderating Role of Joke Teller Gender and Severity of Sexual Assault.}, journal = {Violence against women}, volume = {23}, number = {8}, pages = {951-972}, doi = {10.1177/1077801216654017}, pmid = {27386879}, issn = {1552-8448}, mesh = {Adolescent ; Adult ; Humans ; Interpersonal Relations ; Male ; Pilot Projects ; Sexism/psychology ; Sexual Behavior ; Sexual Harassment/*psychology ; Spain ; Students/*psychology/statistics & numerical data ; Surveys and Questionnaires ; Universities/organization & administration/statistics & numerical data ; Wit and Humor as Topic/*psychology ; }, abstract = {Three experiments examined the effect of sexist humor on men's self-reported rape proclivity (RP). Pilot study demonstrated that people differentiate the five rape scenarios of Bohner et al.'s. RP Scale based on the degree of physical violence perpetrated against the victim. Experiment 1 demonstrated that men higher in hostile sexism report greater RP upon exposure to sexist jokes when a woman (vs. a man) delivers them, and that this effect is limited to rape scenarios depicting a moderate versus a high level of physical violence. Experiment 2 further demonstrated that the relationship between hostile sexism and rape proclivity in response to a moderately violent rape scenario after exposure to sexist humor generalizes beyond women in the immediate humor context to women as a whole.}, } @article {pmid27380111, year = {2017}, author = {Uzun, S and Pehlivan, E}, title = {Comment on Ersan et al.'s "Evaluation of Macular Ganglion Cell-inner Plexiform Layer and Choroid in Psoriasis Patients Using Enhanced Depth Imaging Spectral Domain Optical Coherence Tomography".}, journal = {Ocular immunology and inflammation}, volume = {25}, number = {4}, pages = {525}, doi = {10.1080/09273948.2016.1180403}, pmid = {27380111}, issn = {1744-5078}, mesh = {Choroid ; Humans ; *Psoriasis ; Retina ; *Tomography, Optical Coherence ; }, } @article {pmid27377310, year = {2016}, author = {Zhang, X and Tan, X and Weng, J and Li, Y}, title = {LOCC indistinguishable orthogonal product quantum states.}, journal = {Scientific reports}, volume = {6}, number = {}, pages = {28864}, pmid = {27377310}, issn = {2045-2322}, abstract = {We construct two families of orthogonal product quantum states that cannot be exactly distinguished by local operation and classical communication (LOCC) in the quantum system of (2k+i) ⊗ (2l+j) (i, j ∈ {0, 1} and i ≥ j) and (3k+i) ⊗ (3l+j) (i, j ∈ {0, 1, 2} ). And we also give the tiling structure of these two families of quantum product states where the quantum states are unextendible in the first family but are extendible in the second family. Our construction in the quantum system of (3k+i) ⊗ (3l+j) is more generalized than the other construction such as Wang et al.'s construction and Zhang et al.'s construction, because it contains the quantum system of not only (2k) ⊗ (2l) and (2k+1) ⊗ (2l) but also (2k) ⊗ (2l+1) and (2k+1) ⊗ (2l+1). We calculate the non-commutativity to quantify the quantumness of a quantum ensemble for judging the local indistinguishability. We give a general method to judge the indistinguishability of orthogonal product states for our two constructions in this paper. We also extend the dimension of the quantum system of (2k) ⊗ (2l) in Wang et al.'s paper. Our work is a necessary complement to understand the phenomenon of quantum nonlocality without entanglement.}, } @article {pmid27376917, year = {2016}, author = {Shen, Z and Sun, J and Cao, J and Zhang, L and Zhang, Q and Lei, Y and Gao, J and Huang, RJ and Liu, S and Huang, Y and Zhu, C and Xu, H and Zheng, C and Liu, P and Xue, Z}, title = {Chemical profiles of urban fugitive dust PM2.5 samples in Northern Chinese cities.}, journal = {The Science of the total environment}, volume = {569-570}, number = {}, pages = {619-626}, doi = {10.1016/j.scitotenv.2016.06.156}, pmid = {27376917}, issn = {1879-1026}, mesh = {Aerosols/analysis ; Air Pollutants/*analysis ; China ; Cities ; Dust/*analysis ; *Environmental Monitoring ; Particle Size ; Particulate Matter/*analysis ; }, abstract = {Urban fugitive dust PM2.5 samples were collected in 11 selected cities in North China, and 9 ions (SO4(2-), NO3(-), Cl(-), F(-), Na(+), NH4(+), K(+), Mg(2+), and Ca(2+)) and 22 elements (Si, Al, S, Cl, K, Ca, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, Br, Rb, Sr, Sn, Sb, Ba, and Pb) were determined to investigate chemical profiles of PM2.5. The coefficient of divergence (CD) was used to compare the similarities of the chemical profiles for fugitive dust among three regions in North China, and the results showed that their composition are quite similar. Total water soluble ions occupied 9.3% and 10.0% on average of road dust and construction dust, respectively, indicating that most of the materials in urban fugitive dust samples were insoluble. Ca(2+) was the most abundant cation and SO4(2-) dominated in anions. Soil dust loading was calculated to occupy 70.8% and 83.6% in road dust and construction dust, respectively. Ca, Si, Fe, and Al were the most abundant elements in all the samples, and Ca was absolutely the most abundant specie among the 22 detected elements in construction dust samples. Chemical species ratios were used to highlight the characteristics of urban fugitive dust by comparing with other types of aerosols. High Ca/Al ratio was a good marker to distinguish urban fugitive dust from Asian dust and Chinese loess. In addition, low K(+)/K and NO3(-)/SO4(2-), and high Zn/Al and Pb/Al ratios were good indicators to separate urban fugitive dust from desert dust, Chinese loess, or urban PM2.5 samples.}, } @article {pmid27365017, year = {2016}, author = {Brittain, EH and Proschan, MA}, title = {Comments on Berry et al.'s response-adaptive randomization platform trial for Ebola.}, journal = {Clinical trials (London, England)}, volume = {13}, number = {5}, pages = {566-567}, doi = {10.1177/1740774516654440}, pmid = {27365017}, issn = {1740-7753}, mesh = {Hemorrhagic Fever, Ebola/*therapy ; Humans ; Random Allocation ; *Randomized Controlled Trials as Topic ; Research Design ; }, } @article {pmid27362267, year = {2017}, author = {Montoya, AK and Hayes, AF}, title = {Two-condition within-participant statistical mediation analysis: A path-analytic framework.}, journal = {Psychological methods}, volume = {22}, number = {1}, pages = {6-27}, doi = {10.1037/met0000086}, pmid = {27362267}, issn = {1939-1463}, mesh = {*Effect Modifier, Epidemiologic ; Humans ; *Models, Statistical ; *Monte Carlo Method ; }, abstract = {Researchers interested in testing mediation often use designs where participants are measured on a dependent variable Y and a mediator M in both of 2 different circumstances. The dominant approach to assessing mediation in such a design, proposed by Judd, Kenny, and McClelland (2001), relies on a series of hypothesis tests about components of the mediation model and is not based on an estimate of or formal inference about the indirect effect. In this article we recast Judd et al.'s approach in the path-analytic framework that is now commonly used in between-participant mediation analysis. By so doing, it is apparent how to estimate the indirect effect of a within-participant manipulation on some outcome through a mediator as the product of paths of influence. This path-analytic approach eliminates the need for discrete hypothesis tests about components of the model to support a claim of mediation, as Judd et al.'s method requires, because it relies only on an inference about the product of paths-the indirect effect. We generalize methods of inference for the indirect effect widely used in between-participant designs to this within-participant version of mediation analysis, including bootstrap confidence intervals and Monte Carlo confidence intervals. Using this path-analytic approach, we extend the method to models with multiple mediators operating in parallel and serially and discuss the comparison of indirect effects in these more complex models. We offer macros and code for SPSS, SAS, and Mplus that conduct these analyses. (PsycINFO Database Record}, } @article {pmid27345698, year = {2016}, author = {Gleason, SM and Westoby, M and Jansen, S and Choat, B and Brodribb, TJ and Cochard, H and Delzon, S and Hacke, UG and Jacobsen, AL and Johnson, DM and Lens, F and Maherali, H and Martínez-Vilalta, J and Mayr, S and McCulloh, KA and Morris, H and Nardini, A and Plavcová, L and Pratt, RB and Schreiber, SG and Zanne, AE}, title = {On research priorities to advance understanding of the safety-efficiency tradeoff in xylem: A response to Bittencourt et al.'s (2016) comment 'On xylem hydraulic efficiencies, wood space-use and the safety-efficiency tradeoff': in this issue of New Phytologist, pp. 1152-1155.}, journal = {The New phytologist}, volume = {211}, number = {4}, pages = {1156-1158}, doi = {10.1111/nph.14043}, pmid = {27345698}, issn = {1469-8137}, mesh = {Plant Transpiration ; Water ; *Wood ; *Xylem ; }, } @article {pmid27335503, year = {2016}, author = {Feng, P and Miao, C and Bullard, JW}, title = {Factors influencing the stability of AFm and AFt in the Ca-Al-S-O-H system at 25 °C.}, journal = {Journal of the American Ceramic Society. American Ceramic Society}, volume = {99}, number = {3}, pages = {1031-1041}, doi = {10.1111/jace.13971}, pmid = {27335503}, issn = {0002-7820}, support = {9999-NIST/ImNIST/Intramural NIST DOC/United States ; }, abstract = {The stabilities of Al2O3-Fe2O3-mono (AFm) and -tri (AFt) phases in the Ca-Al-S-O-H system at 25 °C are examined using Gibbs energy minimization as implemented by GEM-Selektor software coupled with the Nagra/PSI thermodynamic database. Equilibrium phase diagrams are constructed and compared to those reported in previous studies. The sensitivity of the calculations to the assumed solid solubility products, highlighted by the example of hydrogarnet, is likely the reason why some studies, including this one, predict a stable SO4-rich AFm phase while others do not. The majority of the effort is given to calculating the influences on AFm and AFt stability of alkali and carbonate components, both of which are typically present in cementitious binders. Higher alkali content shifts the equilibria of both AFt and AFm to lower Ca but higher Al and S concentrations in solution. More importantly, higher alkali content significantly expands the range of solution compositions in equilibrium with AFm relative to AFt phases. The introduction of carbonates alters not only the stable AFm solid solution compositions, as expected, but also influences the range of solution pH over which SO4-rich and OH-rich AFm phases are dominant. Some experimental tests are suggested that could provide validation of these calculations, which are all the more important because of the implications for resistance of portland cement binders to external sulfate attack.}, } @article {pmid27306765, year = {2016}, author = {Masters, RK and Powers, DA and Hummer, RA and Beck, A and Lin, SF and Finch, BK}, title = {Fitting Age-Period-Cohort Models Using the Intrinsic Estimator: Assumptions and Misapplications.}, journal = {Demography}, volume = {53}, number = {4}, pages = {1253-1259}, pmid = {27306765}, issn = {1533-7790}, support = {P2C HD042849/HD/NICHD NIH HHS/United States ; P2C HD050924/HD/NICHD NIH HHS/United States ; P2C HD066613/HD/NICHD NIH HHS/United States ; R01 MD004025/MD/NIMHD NIH HHS/United States ; }, mesh = {*Age Factors ; Humans ; *Research Design ; }, abstract = {We thank Demography’s editorial office for the opportunity to respond to te Grotenhuis et al.’s commentary regarding the methods used and the results presented in our earlier paper (Masters et al. 2014). In this response, we briefly reply to three general themes raised in the commentary: (1) the presentation and discussion of APC results, (2) the fitting of full APC models to data for which a simpler model holds, and (3) the variation in the estimated age, period, and cohort coefficients produced by the intrinsic estimator (IE) (i.e., the “non-uniqueness property” of the IE, as referred to by Pelzer et al. (2015)).}, } @article {pmid27301642, year = {2017}, author = {Chien, CW and Bagraith, KS and Khan, A and Deen, M and Syu, JJ and Strong, J}, title = {Establishment of cutpoints to categorize the severity of chronic pain using composite ratings with Rasch analysis.}, journal = {European journal of pain (London, England)}, volume = {21}, number = {1}, pages = {82-91}, doi = {10.1002/ejp.906}, pmid = {27301642}, issn = {1532-2149}, mesh = {Adult ; Aged ; Chronic Pain/*classification/*diagnosis/psychology ; Cohort Studies ; Female ; Humans ; Male ; Middle Aged ; Pain Measurement ; Quality of Life ; Severity of Illness Index ; }, abstract = {BACKGROUND: Establishment of cutpoints for classifying mild, moderate and severe pain is commonly based on single rating of worst or average pain. However, single pain measure may serve as a brief and partial surrogate for composite pain ratings. This study aimed to base composite pain ratings to establish optimal cutpoint that maximized the difference of pain interference on daily function and compare its utility with those based on single worst and average pain.

METHODS: Data were from a cohort study of 322 patients with chronic pain. Brief pain inventory (including four items measuring the least, worst, average and current pain) was administered. Rasch analysis and Serlin et al.'s (Pain, 61, 1995, 277) method were used to derive optimal cutpoint.

RESULTS: Rasch analysis calibrated the least, worst, average and current pain items into a unidimensional hierarchy and produced composite pain measurement. The optimal cutpoint for composite pain (mild, ≤4; moderate, >4-6; severe, >6-10 on the 0-10 numeric rating scale) differed from those cutpoints for worst (≤6; >6-8; >8-10) and average pain (≤5; >5-7; >7-10). The optimal cutpoint for composite pain was better able than those for worst and average pain to distinguish among groups on patient-rated pain quality and quality of life. The optimal cutpoint for average pain had better discriminant ability than that for worst pain.

CONCLUSION: The results suggest that using optimal cutpoint for composite pain may be useful to classify clinically important groups in patients with chronic pain and that average pain may be an alternative choice if a single item is used. WHAT DOES THIS STUDY ADD?: Using composite pain, optimal classification for mild, moderate and severe pain exhibited better discriminant ability than using single worst/average pain. The difficulty hierarchy of the least, worst, average and current pain helps to screen people with irregular responses.}, } @article {pmid27274573, year = {2016}, author = {Groenendyk, E}, title = {The Anxious and Ambivalent Partisan: The Effect of Incidental Anxiety on Partisan Motivated Recall and Ambivalence.}, journal = {Public opinion quarterly}, volume = {80}, number = {2}, pages = {460-479}, pmid = {27274573}, issn = {0033-362X}, abstract = {Affective Intelligence Theory (AIT) asserts that anxiety reduces the effect of party identification on candidate preferences (Marcus, Neuman, and MacKuen 2000), but recent studies have raised doubts about this causal claim. Rather than functioning as a moderator of party identification, perhaps anxiety has a direct effect on preferences, or perhaps the relationship is reversed and preferences drive emotions (Ladd and Lenz 2008). Alternatively, Marcus et al.'s measure of anxiety may simply be capturing partisan ambivalence, so the posited relationship is spurious (Lavine, Johnston, and Steenbergen 2012). This paper addresses each of these questions by examining the effect of experimentally induced emotions on the types of considerations that came to mind when a national sample of adult Americans was asked what they liked and disliked about Barack Obama. By directly manipulating anxiety, this experiment avoids the causal ambiguity plaguing this debate and ascertains the true nature of the relationship between anxiety and ambivalence. Consistent with AIT, anxiety led respondents to recall more contemporary considerations, whereas enthusiasm brought to mind more long-standing considerations. Because the political context at the time of the study (fall 2013) was a very tumultuous time for the Obama administration, the increased accessibility of contemporary considerations led Democratic participants to experience more ambivalence in the anxiety condition. This effect was concentrated among those Democrats who were exposed to the most newspaper coverage.}, } @article {pmid27270924, year = {2016}, author = {Brown, NJ and MacDonald, DA and Samanta, MP and Friedman, HL and Coyne, JC}, title = {More Questions than Answers: Continued Critical Reanalysis of Fredrickson et al.'s Studies of Genomics and Well-Being.}, journal = {PloS one}, volume = {11}, number = {6}, pages = {e0156415}, pmid = {27270924}, issn = {1932-6203}, mesh = {*Gene Expression Regulation ; Genomics/*methods ; Humans ; }, abstract = {We critically re-examine Fredrickson et al.'s renewed claims concerning the differential relationship between hedonic and eudaimonic forms of well-being and gene expression, namely that people who experience a preponderance of eudaimonic well-being have gene expression profiles that are associated with more favorable health outcomes. By means of an extensive reanalysis of their data, we identify several discrepancies between what these authors claimed and what their data support; we further show that their different analysis models produce mutually contradictory results. We then show how Fredrickson et al.'s most recent article on this topic not only fails to adequately address our previously published concerns about their earlier related work, but also introduces significant further problems, including inconsistency in their hypotheses. Additionally, we demonstrate that regardless of which statistical model is used to analyze their data, Fredrickson et al.'s method can be highly sensitive to the inclusion (or exclusion) of data from a single subject. We reiterate our previous conclusions, namely that there is no evidence that Fredrickson et al. have established a reliable empirical distinction between their two delineated forms of well-being, nor that eudaimonic well-being provides any overall health benefits over hedonic well-being.}, } @article {pmid27270915, year = {2016}, author = {Tsai, TH and Chang, HT and Ho, YL}, title = {Perceptions of a Specific Family Communication Application among Grandparents and Grandchildren: An Extension of the Technology Acceptance Model.}, journal = {PloS one}, volume = {11}, number = {6}, pages = {e0156680}, pmid = {27270915}, issn = {1932-6203}, mesh = {Adult ; Aged ; Female ; Grandparents/*psychology ; Humans ; Internet ; Male ; Middle Aged ; Models, Psychological ; Pedigree ; *Perception ; Self Efficacy ; *Social Networking ; User-Computer Interface ; Young Adult ; }, abstract = {Many studies have noted that the use of social networks sites (SNSs) can enhance social interaction among the elderly and that the motivation for the elderly to use SNSs is to keep in contact with remote friends and family or the younger generation. Memotree is designed to promote intergenerational family communication. The system incorporates the Family Tree design concept and provides family communication mechanisms based on the Family Communication Scale. In addition, the system optimizes hardware and interface use to conform to the specific needs of older and substantially younger individuals. Regarding the impact of variables on SNS with respect to the interaction of usability variables in the construction of a cross-generational communication platform, we adopted the TAM model and Chung et al.'s suggestions to promote user acceptance of the proposed Memotree system. A total of 39 grandchildren and 39 grandparents met the criteria and were included in the study. The elderly and young respondents revealed substantial willingness to use and/or satisfaction with using the Memotree system. Empirical results indicate that technology affordances and perceived ease of use have a positive impact on perceived usefulness, while perceived ease of use is affected by technology affordances. Internet self-efficacy and perceived usefulness have a positive impact on the user's behavioral intention toward the system. In addition, this study investigated age as a moderating variable in the model. The results indicate that grandchildren have a larger significant effect on the path between perceived usefulness and behavioral intention than grandparents. This study proposes a more complete framework for investigating the user's behavioral intention and provides a more appropriate explanation of related services for cross-generational interaction with SNS services.}, } @article {pmid27240068, year = {2016}, author = {Schmitz, I and Prymak, O and Epple, M and Ernert, C and Tannapfel, A}, title = {Squamous cell carcinoma in association with a red tattoo.}, journal = {Journal der Deutschen Dermatologischen Gesellschaft = Journal of the German Society of Dermatology : JDDG}, volume = {14}, number = {6}, pages = {604-609}, doi = {10.1111/ddg.12730}, pmid = {27240068}, issn = {1610-0387}, mesh = {Adult ; Carcinoma, Squamous Cell/*etiology ; Color ; Coloring Agents ; Female ; Humans ; Skin Neoplasms/*etiology ; Tattooing/*adverse effects ; Young Adult ; }, abstract = {BACKGROUND AND OBJECTIVES: Although tattoos have become exceedingly popular in recent years, only few cases of severe reactions leading to malignant transformation have been reported in the literature. This stands in contrast to the virtually innumerable number of tattoos worldwide. The composition of tattoo dyes is highly variable, and even the same colors may contain different compounds. The objective of our study was to investigate in what way tattoo dyes may potentially trigger skin cancer.

PATIENT AND METHODS: We report the rare case of a 24-year-old woman who - seven months after getting a tattoo on the back of her foot - developed a squamous cell carcinoma in close proximity to the red dye used. Complications started in the form of nonspecific swelling. The lesion was histologically examined. The composition of the incorporated dye was analyzed using scanning electron microscopy in combination with energy dispersive element analysis. Thermogravimetry and powder diffraction were used for further characterization.

RESULTS AND CONCLUSIONS: While the tattoo dye primarily consisted of barium sulfate, traces of Al, S, Ti, P, Mg, and Cl were also detected. The analysis showed pigment granules of varying sizes. In rare cases, tattoo inks may have carcinogenic effects, which appear to be multifactorial.}, } @article {pmid27240067, year = {2016}, author = {Schmitz, I and Prymak, O and Epple, M and Ernert, C and Tannapfel, A}, title = {Plattenepithelkarzinom in Verbindung mit einer roten Tätowierung.}, journal = {Journal der Deutschen Dermatologischen Gesellschaft = Journal of the German Society of Dermatology : JDDG}, volume = {14}, number = {6}, pages = {604-610}, doi = {10.1111/ddg.12730_g}, pmid = {27240067}, issn = {1610-0387}, abstract = {HINTERGRUND UND ZIELE: Obwohl Tätowierungen in den letzten Jahren außerordentlich beliebt geworden sind, wurde in der Literatur bisher nur über wenige Fälle schwerer Reaktionen berichtet, die zu einer malignen Transformation führten. Dies steht im Kontrast zu der praktisch unüberschaubaren Zahl an Tätowierungen weltweit. Die Zusammensetzung der für Tätowierungen verwendeten Farbstoffe variiert stark, und selbst gleiche Farbtöne können unterschiedliche Komponenten enthalten. Das Ziel unserer Studie war es zu untersuchen, auf welche Weise Tätowierungen möglicherweise Hautkrebs auslösen können.

PATIENTEN UND METHODEN: Wir berichten über den seltenen Fall einer 24-jährigen Frau, bei der sich sieben Monate nachdem sie eine Tätowierung auf dem Fußrücken erhalten hatte in unmittelbarer Nähe des verwendeten roten Farbstoffs ein Plattenepithelkarzinom entwickelte. Die Komplikationen begannen mit einer unspezifischen Schwellung. Die Läsion wurde histologisch untersucht. Die Zusammensetzung des inkorporierten Farbstoffs wurde mittels Rasterelektronenmikroskopie in Kombination mit energiedispersiver Elementanalyse analysiert. Zur weiteren Charakterisierung wurden Thermogravimetrie und Pulverdiffraktometrie eingesetzt.

Der Tätowierungsfarbstoff enthielt hauptsächlich Bariumsulfat; Spuren von Al, S, Ti, P, Mg und Cl ließen sich ebenfalls nachweisen. Bei der Analyse zeigten sich Pigmentgranula unterschiedlicher Größe. In seltenen Fällen kann Tätowierungstinte karzinogene Effekte haben, die multifaktoriell zu sein scheinen.}, } @article {pmid27232768, year = {2017}, author = {Glue, P and Loo, C and Rodgers, A and Gálvez, V and Somogyi, AA and Mitchell, PB}, title = {Comments on Cooper et al.'s review on strategies to mitigate dissociative and psychotomimetic effects from ketamine when used as a fast-acting antidepressant.}, journal = {The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry}, volume = {18}, number = {6}, pages = {489}, doi = {10.1080/15622975.2016.1181782}, pmid = {27232768}, issn = {1814-1412}, mesh = {Antidepressive Agents ; *Depressive Disorder, Major ; Excitatory Amino Acid Antagonists ; Humans ; *Ketamine ; }, } @article {pmid27219533, year = {2016}, author = {Masip, J and Blandón-Gitlin, I and de la Riva, C and Herrero, C}, title = {An empirical test of the decision to lie component of the Activation-Decision-Construction-Action Theory (ADCAT).}, journal = {Acta psychologica}, volume = {169}, number = {}, pages = {45-55}, doi = {10.1016/j.actpsy.2016.05.004}, pmid = {27219533}, issn = {1873-6297}, mesh = {Adolescent ; Adult ; Criminology/education ; *Deception ; *Decision Making ; Female ; Humans ; Judgment ; Male ; Motivation ; Probability ; *Psychological Theory ; Students/psychology ; *Truth Disclosure ; }, abstract = {Meta-analyses reveal that behavioral differences between liars and truth tellers are small. To facilitate lie detection, researchers are currently developing interviewing approaches to increase these differences. Some of these approaches assume that lying is cognitively more difficult than truth telling; however, they are not based on specific cognitive theories of lie production, which are rare. Here we examined one existing theory, Walczyk et al.'s (2014) Activation-Decision-Construction-Action Theory (ADCAT). We tested the Decision component. According to ADCAT, people decide whether to lie or tell the truth as if they were using a specific mathematical formula to calculate the motivation to lie from (a) the probability of a number of outcomes derived from lying vs. telling the truth, and (b) the costs/benefits associated with each outcome. In this study, participants read several hypothetical scenarios and indicated whether they would lie or tell the truth in each scenario (Questionnaire 1). Next, they answered several questions about the consequences of lying vs. telling the truth in each scenario, and rated the probability and valence of each consequence (Questionnaire 2). Significant associations were found between the participants' dichotomous decision to lie/tell the truth in Questionnaire 1 and their motivation to lie scores calculated from the Questionnaire 2 data. However, interestingly, whereas the expected consequences of truth telling were associated with the decision to lie vs. tell the truth, the expected consequences of lying were not. Suggestions are made to refine ADCAT, which can be a useful theoretical framework to guide deception research.}, } @article {pmid27218005, year = {2016}, author = {Liu, W and Xie, Q and Wang, S and Hu, B}, title = {An improved authenticated key agreement protocol for telecare medicine information system.}, journal = {SpringerPlus}, volume = {5}, number = {}, pages = {555}, pmid = {27218005}, issn = {2193-1801}, abstract = {In telecare medicine information systems (TMIS), identity authentication of patients plays an important role and has been widely studied in the research field. Generally, it is realized by an authenticated key agreement protocol, and many such protocols were proposed in the literature. Recently, Zhang et al. pointed out that Islam et al.'s protocol suffers from the following security weaknesses: (1) Any legal but malicious patient can reveal other user's identity; (2) An attacker can launch off-line password guessing attack and the impersonation attack if the patient's identity is compromised. Zhang et al. also proposed an improved authenticated key agreement scheme with privacy protection for TMIS. However, in this paper, we point out that Zhang et al.'s scheme cannot resist off-line password guessing attack, and it fails to provide the revocation of lost/stolen smartcard. In order to overcome these weaknesses, we propose an improved protocol, the security and authentication of which can be proven using applied pi calculus based formal verification tool ProVerif.}, } @article {pmid27211684, year = {2016}, author = {Aral, S and Beşe, AV}, title = {Convective drying of hawthorn fruit (Crataegus spp.): Effect of experimental parameters on drying kinetics, color, shrinkage, and rehydration capacity.}, journal = {Food chemistry}, volume = {210}, number = {}, pages = {577-584}, doi = {10.1016/j.foodchem.2016.04.128}, pmid = {27211684}, issn = {1873-7072}, mesh = {Chemical Phenomena ; Color ; *Crataegus ; Desiccation/*methods ; Diffusion ; Fruit/*chemistry ; Kinetics ; Models, Theoretical ; Plant Extracts ; Temperature ; Thermodynamics ; Water/chemistry ; }, abstract = {Thin layer drying characteristics and physicochemical properties of hawthorn fruit (Crataegus spp.) were investigated using a convective dryer at air temperatures 50, 60 and 70°C and air velocities of 0.5, 0.9 and 1.3m/s. The drying process of hawthorn took place in the falling rate period, and the drying time decreased with increasing air temperature and velocity. The experimental data obtained during the drying process were fitted to eleven different mathematical models. The Midilli et al.'s model was found to be the best appropriate model for explaining the drying behavior of hawthorn fruit. Effective moisture diffusion coefficients (Deff) were calculated by Fick's diffusion model and their values varied from 2.34×10(-10)m(2)/s to 2.09×10(-9)m(2)/s. An Arrhenius-type equation was applied to determine the activation energies. While the shrinkage decreased, the rehydration ratio increased with increasing air temperature and air velocity.}, } @article {pmid27207734, year = {2016}, author = {Tabacchi, ME and Cardaci, M}, title = {Preferential Biases for Texts That Include Neuroscientific Jargon.}, journal = {Psychological reports}, volume = {118}, number = {3}, pages = {793-803}, doi = {10.1177/0033294116649000}, pmid = {27207734}, issn = {1558-691X}, mesh = {Adult ; *Choice Behavior ; Female ; Humans ; Male ; *Neurosciences ; Students/*psychology ; Universities ; Young Adult ; }, abstract = {The results of an experiment of preferential biases for texts that include neuroscientific jargon are presented. Such preferential bias has been reported even when the presented jargon is meaningless. In a variation of the well-known Weisberg et al. experiment, a group of undergraduate students (N = 150; females 48%, males 52%, other 0%; M age = 22.4 year, SD = 2.6) chose between two possible explanations for a psychological phenomenon: a correct explanation or a circular restatement of facts. Unrelated neuroscientific terms were added to one of the explanations. Participants were asked to choose the correct explanation. There was a statistically significant preference for the explanation without neuroscientific terms. These findings differ from Weisberg et al.'s experiment and a number of others. The implications of this discrepancy are discussed.}, } @article {pmid27197632, year = {2016}, author = {Spataro, P and Saraulli, D and Oriolo, D and Costanzi, M and Zanetti, H and Cestari, V and Rossi-Arnaud, C}, title = {Memory in pregnancy and post-partum: Item specific and relational encoding processes in recall and recognition.}, journal = {Scandinavian journal of psychology}, volume = {57}, number = {4}, pages = {271-277}, doi = {10.1111/sjop.12293}, pmid = {27197632}, issn = {1467-9450}, mesh = {Adult ; Cross-Sectional Studies ; Female ; Humans ; *Mental Recall ; Postpartum Period/*psychology ; Pregnancy/*psychology ; *Recognition, Psychology ; Semantics ; }, abstract = {It has been recently proposed that pregnant women would perform memory tasks by focusing more on item-specific processes and less on relational processing, compared to post-partum women (Mickes, Wixted, Shapiro & Scarff,). The present cross-sectional study tested this hypothesis by directly manipulating the type of encoding employed in the study phase. Pregnant, post-partum and control women either rated the pleasantness of word meaning (which induced item-specific elaboration) or named the semantic category to which they belonged (which induced relational elaboration). Memory for the encoded words was later tested in free recall (which emphasizes relational processing) and in recognition (which emphasizes item-specific processing). In line with Mickes et al.'s () conclusions, pregnant women in the item-specific condition performed worse than post-partum women in the relational condition in free recall, but not in recognition. However, compared to the other two groups, pregnant women also exhibited lower recognition accuracy in the item-specific condition. Overall, these results confirm that pregnant women rely on relational encoding less than post-partum women, but additionally suggest that the former group might use item-specific processes less efficiently than post-partum and control women.}, } @article {pmid27192955, year = {2016}, author = {Herrington, JD}, title = {Commentary: Cognitive and emotional empathy in transdiagnostic research - reflections on Klapwijk et al. (2016).}, journal = {Journal of child psychology and psychiatry, and allied disciplines}, volume = {57}, number = {6}, pages = {748-749}, doi = {10.1111/jcpp.12554}, pmid = {27192955}, issn = {1469-7610}, mesh = {*Autism Spectrum Disorder ; Cognition ; Conduct Disorder/psychology ; Emotions ; *Empathy ; Humans ; }, abstract = {Evidence across multiple disorders indicates that empathy is a transdiagnostic dimension of psychopathology. Klapwijk et al.'s (2016) functional MRI study examines whether autism spectrum disorder (ASD) and conduct disorder (CD) can be distinguished by the constructs of 'cognitive' and 'emotional' empathy - with the former focusing on accurate emotion perception and the latter on shared affective experience. This commentary examines the implications of the cognitive/emotional empathy distinction, and how it fits with existing accounts of perceptual differences in ASD. Cognitive empathy overlaps substantially with the constructs of emotion perception and Theory of Mind - both well studied among individuals with ASD, but generally viewed as fairly distinct from empathy. CD, on the other hand, is typically not associated with frank perceptual deficits. Although the brain imaging data from this study do not provide strong support for the constructs of cognitive and emotional empathy, the general approach used in this study is precisely the kind needed to test the validity and utility of transdiagnostic mechanisms of psychopathology.}, } @article {pmid27191950, year = {2016}, author = {Li, X and Xu, X and You, X and Truhlar, DG}, title = {Benchmark Calculations for Bond Dissociation Enthalpies of Unsaturated Methyl Esters and the Bond Dissociation Enthalpies of Methyl Linolenate.}, journal = {The journal of physical chemistry. A}, volume = {120}, number = {23}, pages = {4025-4036}, doi = {10.1021/acs.jpca.6b02600}, pmid = {27191950}, issn = {1520-5215}, abstract = {It is important to determine an appropriate computational method for obtaining accurate thermochemical properties of large biodiesel molecules such as methyl linolenate. In this study, we use Kohn-Sham density functional theory (DFT) and coupled cluster theory to calculate bond dissociation enthalpies (BDEs) of seven fragment molecules of methyl linolenate, in particular, propene, methyl formate, cis-3-hexene, 1,4-pentadiene, 1-pentene, butane, and methyl butanoate. The results are compared to BDEs obtained from experiments and to Oyeyemi et al.'s multireference averaged coupled pair functional (MRACPF2) calculations. We found that with extrapolation to the complete basis set (CBS) limit, the BDEs derived from coupled cluster calculations with single, double, and triple excitations (CCSDT) and from CCSDT with a perturbative treatment of connected quadruple excitations, CCSDT(2)Q/CBS, are closer to the available experimental values than those obtained by MRACPF2 for propene and methyl formate. The CCSDT/CBS calculations were chosen as the reference for validating the DFT methods. Among the density functionals, we found that M08-HX has the best performance with a mean unsigned deviation (MUD) from CCSDT/CBS of only 1.0 kcal/mol, whereas the much more expensive MRACPF2 has an MUD of 1.1 kcal/mol. We then used the most successfully validated density functionals to calculate the BDEs of methyl linolenate and compared the results with the MRACPF2 BDEs. The present study identifies several Kohn-Sham exchange-correlation functionals that should be useful for modeling ester combustion, especially the M08-HX, M06-2X, M05-2X, M08-SO, and MPWB1K global-hybrid meta functionals, the M11 and MN12-SX range-separated-hybrid meta functionals, the ωB97 range-separated hybrid gradient approximation functional, and the SOGGA11-X global-hybrid gradient approximation functional.}, } @article {pmid27188625, year = {2016}, author = {Mage, DT and Donner, EM}, title = {Comment on Fard et al.'s Candidate gene variants of the immune system and sudden infant death syndrome.}, journal = {International journal of legal medicine}, volume = {130}, number = {4}, pages = {1069-1070}, pmid = {27188625}, issn = {1437-1596}, support = {001/WHO_/World Health Organization/International ; }, mesh = {Humans ; *Immune System ; Infant ; Sudden Infant Death/*genetics ; }, } @article {pmid27183192, year = {2016}, author = {Wilkinson, F and Haque, Y and Or, CC and Gottlieb, AS and Wilson, HR}, title = {Detection of periodic motion trajectories: Effects of frequency and radius.}, journal = {Journal of vision}, volume = {16}, number = {7}, pages = {10}, doi = {10.1167/16.7.10}, pmid = {27183192}, issn = {1534-7362}, mesh = {Adult ; Discrimination, Psychological/*physiology ; Female ; Form Perception/*physiology ; Humans ; Male ; Middle Aged ; *Motion ; Motion Perception/*physiology ; Pattern Recognition, Visual/*physiology ; Photic Stimulation/methods ; *Sensory Thresholds ; Young Adult ; }, abstract = {Periodic trajectories are an important component of biological motion. Or, Thabet, Wilkinson, and Wilson (2011) studied radial frequency (RF) motion trajectory detection and concluded that, for RF2-5 trajectories, the threshold function paralleled that of static RF patterns. We have extended Or et al.'s (2011) findings to a broader range of RFs (three to 24 cycles) and across a 4-fold range of radii (1°-4°). We report that (a) thresholds for RF trajectories decrease as a power function of RF for low RF trajectories (three to six cycles) before approaching an asymptote at high RFs (12-24 cycles); (b) detection thresholds for RF trajectories scale proportionally with radius; and (c) there is no lower versus upper field advantage in the parafoveal field for stimuli displaced from fixation on the vertical midline. The results are compared to earlier findings for static RF thresholds, and we argue that our findings support the existence of parallel spatial and temporal processing channels that may contribute to both action perception and production.}, } @article {pmid27171160, year = {2016}, author = {Lai, YM and Cheng, PJ and Lee, CC and Ku, CY}, title = {A New Ticket-Based Authentication Mechanism for Fast Handover in Mesh Network.}, journal = {PloS one}, volume = {11}, number = {5}, pages = {e0155064}, pmid = {27171160}, issn = {1932-6203}, mesh = {*Algorithms ; *Computer Communication Networks ; Computer Security ; Models, Theoretical ; *Wireless Technology ; }, abstract = {Due to the ever-growing popularity mobile devices of various kinds have received worldwide, the demands on large-scale wireless network infrastructure development and enhancement have been rapidly swelling in recent years. A mobile device holder can get online at a wireless network access point, which covers a limited area. When the client leaves the access point, there will be a temporary disconnection until he/she enters the coverage of another access point. Even when the coverages of two neighboring access points overlap, there is still work to do to make the wireless connection smoothly continue. The action of one wireless network access point passing a client to another access point is referred to as the handover. During handover, for security concerns, the client and the new access point should perform mutual authentication before any Internet access service is practically gained/provided. If the handover protocol is inefficient, in some cases discontinued Internet service will happen. In 2013, Li et al. proposed a fast handover authentication mechanism for wireless mesh network (WMN) based on tickets. Unfortunately, Li et al.'s work came with some weaknesses. For one thing, some sensitive information such as the time and date of expiration is sent in plaintext, which increases security risks. For another, Li et al.'s protocol includes the use of high-quality tamper-proof devices (TPDs), and this unreasonably high equipment requirement limits its applicability. In this paper, we shall propose a new efficient handover authentication mechanism. The new mechanism offers a higher level of security on a more scalable ground with the client's privacy better preserved. The results of our performance analysis suggest that our new mechanism is superior to some similar mechanisms in terms of authentication delay.}, } @article {pmid27167556, year = {2016}, author = {Grim, K and Rosenberg, D and Svedberg, P and Schön, UK}, title = {Shared decision-making in mental health care-A user perspective on decisional needs in community-based services.}, journal = {International journal of qualitative studies on health and well-being}, volume = {11}, number = {}, pages = {30563}, pmid = {27167556}, issn = {1748-2631}, mesh = {Adult ; Cognition ; Communication ; *Community Mental Health Services ; Cooperative Behavior ; *Decision Making ; Female ; Focus Groups ; Humans ; Male ; Mental Disorders/*therapy ; *Mental Health ; Models, Psychological ; *Patient Participation ; Power, Psychological ; *Professional-Patient Relations ; Sweden ; Young Adult ; }, abstract = {BACKGROUND: Shared decision-making (SDM) is an emergent research topic in the field of mental health care and is considered to be a central component of a recovery-oriented system. Despite the evidence suggesting the benefits of this change in the power relationship between users and practitioners, the method has not been widely implemented in clinical practice.

OBJECTIVE: The objective of this study was to investigate decisional and information needs among users with mental illness as a prerequisite for the development of a decision support tool aimed at supporting SDM in community-based mental health services in Sweden.

METHODS: Three semi-structured focus group interviews were conducted with 22 adult users with mental illness. The transcribed interviews were analyzed using a directed content analysis. This method was used to develop an in-depth understanding of the decisional process as well as to validate and conceptually extend Elwyn et al.'s model of SDM.

RESULTS: The model Elwyn et al. have created for SDM in somatic care fits well for mental health services, both in terms of process and content. However, the results also suggest an extension of the model because decisions related to mental illness are often complex and involve a number of life domains. Issues related to social context and individual recovery point to the need for a preparation phase focused on establishing cooperation and mutual understanding as well as a clear follow-up phase that allows for feedback and adjustments to the decision-making process.

The current study contributes to a deeper understanding of decisional and information needs among users of community-based mental health services that may reduce barriers to participation in decision-making. The results also shed light on attitudinal, relationship-based, and cognitive factors that are important to consider in adapting SDM in the mental health system.}, } @article {pmid27166690, year = {2016}, author = {Harrison, WJ and Bex, PJ}, title = {Reply to Pachai et al.}, journal = {Current biology : CB}, volume = {26}, number = {9}, pages = {R353-4}, pmid = {27166690}, issn = {1879-0445}, support = {R01 EY019281/EY/NEI NIH HHS/United States ; R01 EY021553/EY/NEI NIH HHS/United States ; R01 EY029713/EY/NEI NIH HHS/United States ; }, mesh = {Contrast Sensitivity ; *Discrimination, Psychological ; Humans ; *Pattern Recognition, Visual ; Perceptual Masking ; *Space Perception ; *Visual Fields ; }, abstract = {Peripheral vision is fundamentally limited by the spacing between objects. When asked to report a target's identity, observers make erroneous reports that sometimes match the identity of a nearby distractor and sometimes match a combination of target and distractor features. The classification of these errors has previously been used to support competing 'substitution' [1] or 'averaging' [2] models of the phenomenon known as 'visual crowding'. We recently proposed a single model in which both classes of error occur because observers make their reports by sampling from a biologically-plausible population of weighted responses within a region of space around the target [3]. It is critical to note that there is no probabilistic substitution or averaging process in our model; instead, we argue that neither substitution nor averaging occur, but that these are misclassifications of the distribution of reports that emerge when a population response distribution is sampled. This is a fundamentally different way of thinking about crowding, and on this basis we claim to have provided a mechanism unifying categorically distinct perceptual errors. Our goal was not to model all crowding phenomena, such as the release from crowding when target and flanks differ in color or depth [4]. Pachai et al.[5] have suggested that our model is not unifying because it inaccurately predicts perceptual performance for a particular stimulus. Although we agree that our model does not predict their data, this specific demonstration overlooks the critical aspect of the model: perceptual reports are drawn from a weighted population code. We show that Pachai et al.'s [5] own data actually provide evidence for the population code we have described [3], and we suggest a biologically-plausible analysis of their stimuli that provides a computational basis for their 'grouping' account of crowding.}, } @article {pmid27163786, year = {2016}, author = {Reddy, AG and Das, AK and Odelu, V and Yoo, KY}, title = {An Enhanced Biometric Based Authentication with Key-Agreement Protocol for Multi-Server Architecture Based on Elliptic Curve Cryptography.}, journal = {PloS one}, volume = {11}, number = {5}, pages = {e0154308}, pmid = {27163786}, issn = {1932-6203}, mesh = {Artificial Intelligence ; Biometric Identification/*methods ; Humans ; Pattern Recognition, Automated/*methods ; }, abstract = {Biometric based authentication protocols for multi-server architectures have gained momentum in recent times due to advancements in wireless technologies and associated constraints. Lu et al. recently proposed a robust biometric based authentication with key agreement protocol for a multi-server environment using smart cards. They claimed that their protocol is efficient and resistant to prominent security attacks. The careful investigation of this paper proves that Lu et al.'s protocol does not provide user anonymity, perfect forward secrecy and is susceptible to server and user impersonation attacks, man-in-middle attacks and clock synchronization problems. In addition, this paper proposes an enhanced biometric based authentication with key-agreement protocol for multi-server architecture based on elliptic curve cryptography using smartcards. We proved that the proposed protocol achieves mutual authentication using Burrows-Abadi-Needham (BAN) logic. The formal security of the proposed protocol is verified using the AVISPA (Automated Validation of Internet Security Protocols and Applications) tool to show that our protocol can withstand active and passive attacks. The formal and informal security analyses and performance analysis demonstrates that the proposed protocol is robust and efficient compared to Lu et al.'s protocol and existing similar protocols.}, } @article {pmid27157183, year = {2016}, author = {Ebrahimzadeh, Z and Goodarzi, MA and Joulaei, H}, title = {The Clarification of Depression and Social Support's Contribution to the Prediction of Antiretroviral Medication Adherence and the Rate of CD4 in People with HIV.}, journal = {Global journal of health science}, volume = {8}, number = {9}, pages = {54842}, pmid = {27157183}, issn = {1916-9736}, abstract = {With the development of the antiretroviral therapy, the number of the people with HIV is increasing; therefore, identifying the factors affecting HIV is of great importance. This study aimed to investigate the relationship between the antiretroviral medication adherence and the rate of CD4 with depression and social support in the people with HIV. The research method was a descriptive study kind of correlation. The statistical population included all patients with HIV in Shiraz, of whom, 220 people who had referred to the Behavioral Diseases Consultation Center were selected using the available sampling method. Philips et al.'s Social Support Questionnaire, Beck's Depression Questionnaire II, and ACTG Medication Adherence Questionnaire were used as the research tools. Results were analyzed using the stepwise regression and stepwise hierarchical multiple regression. Regression analysis showed that social support and depression variables could predict totally 47% (P<0.001) of changes of medication adherence variable, and depression could predict only 2% (P<0.01) of rate variance of CD4.}, } @article {pmid27153465, year = {2016}, author = {Tibon Czopp, S and Zeligman, R}, title = {The Rorschach Comprehensive System (CS) Psychometric Validity of Individual Variables.}, journal = {Journal of personality assessment}, volume = {98}, number = {4}, pages = {335-342}, doi = {10.1080/00223891.2015.1131162}, pmid = {27153465}, issn = {1532-7752}, mesh = {Female ; Humans ; Male ; Mental Disorders/*diagnosis ; Psychometrics ; Reproducibility of Results ; Research Design ; Rorschach Test/*standards ; }, abstract = {Since the publication of the Rorschach Inkblot Method (Rorschach, 1921/1942), theorists, researchers, and practitioners have been debating the nature of the task, its conceptual foundation, and most important its psychometric properties. The validity of the Rorschach Comprehensive System (CS; Exner, 1974 , 2003; Exner & Weiner, 1995) has been supported by several meta-analyses that used different types of nontest external criterion for validating individual variables. In a recent meta-analysis, Mihura, Meyer, Dumitrascu, and Bombel (2013) found coefficients ranging from modest to excellent for most of the selected CS variables, with 13 of them reported as showing "little to no support." This article focuses on these variables. Although endorsing Mihura et al.'s mainly validating findings, we also suggest that the evidence presented for the little or no validity of these 13 variables is not quite compelling enough to warrant changing their definition or coding, or removing them from the system. We point to some issues concerning the description and interpretation of these variables and the appropriateness of the external criteria used for exploring their validity, and suggest considering these issues in further CS research. Implications of Mihura et al.'s meta-analysis for clinical and forensic practice are discussed.}, } @article {pmid27148934, year = {2016}, author = {Barr, AB and Sutton, TE and Simons, LG and Wickrama, KA and Lorenz, FO}, title = {Romantic relationship transitions and changes in health among rural, White young adults.}, journal = {Journal of family psychology : JFP : journal of the Division of Family Psychology of the American Psychological Association (Division 43)}, volume = {30}, number = {7}, pages = {832-842}, doi = {10.1037/fam0000207}, pmid = {27148934}, issn = {1939-1293}, mesh = {Adult ; Female ; *Health Status ; Humans ; *Interpersonal Relations ; Iowa/ethnology ; Male ; Rural Population/*statistics & numerical data ; Sexual Partners/*psychology ; Spouses/*ethnology ; White People/*ethnology ; Young Adult ; }, abstract = {A growing body of research examines how the presence and quality of romantic relationships, from dating to marriage, contribute to health. However, this work oftentimes fails to consider instability in the relationship supports and stressors thought to affect health. This is particularly important during the transition to adulthood when instability in romantic relationships is expected to be common. Barr, Culatta, and Simons (2013) put forth a new model that has shown promise for assessing the degree of this instability and its implications for young adult health. They tested their model, however, with an African American sample, and it remains unclear whether it is generalizable to other groups of young adults. The current study considers the generality of their model by applying it to a rural, White sample drawn from the Iowa Youth and Families Project, the only extant data set able to assess both their proposed measurement of relationship instability and its relation to multidimensional measures of health across the transition to adulthood. Findings lend support to their model, yet the degree of instability found among the rural, White young adults in the current study was less than that found in Barr et al.'s (2013) study. (PsycINFO Database Record}, } @article {pmid27148750, year = {2016}, author = {Yu, EA and Chang, EC}, title = {Optimism/pessimism and future orientation as predictors of suicidal ideation: Are there ethnic differences?.}, journal = {Cultural diversity & ethnic minority psychology}, volume = {22}, number = {4}, pages = {572-579}, doi = {10.1037/cdp0000107}, pmid = {27148750}, issn = {1099-9809}, mesh = {Adolescent ; Adult ; Black or African American/psychology ; Asian/psychology ; Female ; Hispanic or Latino/psychology ; Humans ; Male ; Minority Groups/psychology/statistics & numerical data ; Optimism/*psychology ; Pessimism/*psychology ; Predictive Value of Tests ; Students/psychology ; *Suicidal Ideation ; Suicide/*ethnology ; United States/epidemiology/ethnology ; Young Adult ; }, abstract = {OBJECTIVE: The present study sought to test the generalizability of Chang et al.'s (2013) model, which suggests that optimism/pessimism and future orientation function as additive and interactive predictors of suicidal risk, to specific ethnic minority college student groups (i.e., Asian Americans, African Americans, and Latino Americans).

METHOD: The present study used Chang et al.'s (2013) model to predict suicidal ideation among 81 (34 male and 47 female) Asian-American, 71 (22 male and 49 female) African-American adults, and 83 (34 male and 49 female) Latino-American college students.

RESULTS: Our results indicated that this model did not predict suicidal ideation well for Asian-American college students; however, it did work well to predict suicidal ideation for African-American and Latino-American college students.

CONCLUSIONS: Our findings indicate that optimism/pessimism and future orientation are important positive cognitions involved with suicidal ideation for African-American and Latino-American college students. Further research is needed to better understand the cultural underpinnings of how these positive cognitions work to predict suicide-related outcomes. (PsycINFO Database Record}, } @article {pmid27144803, year = {2016}, author = {Çöllü, M and Yüksel, Ş and Şirin, BK and Abbasoğlu, L and Alanay, Y}, title = {Is 1p36 deletion associated with anterior body wall defects?.}, journal = {American journal of medical genetics. Part A}, volume = {170}, number = {7}, pages = {1889-1894}, doi = {10.1002/ajmg.a.37666}, pmid = {27144803}, issn = {1552-4833}, mesh = {Abnormalities, Multiple/*genetics/physiopathology ; Anus, Imperforate/*genetics/physiopathology ; Bladder Exstrophy/physiopathology ; Child, Preschool ; Chromosome Deletion ; Chromosome Disorders/*genetics/physiopathology ; Chromosomes, Human, Pair 1/genetics ; Epispadias/*genetics/physiopathology ; Female ; Genetic Association Studies ; Hernia, Umbilical/*genetics/physiopathology ; Humans ; Male ; Pregnancy ; Prenatal Diagnosis ; Scoliosis/*genetics/physiopathology ; Urogenital Abnormalities/*genetics/physiopathology ; OEIS Complex ; }, abstract = {Epispadias and exstrophy of the cloaca, also known as OEIS complex (omphalocele, exstrophy, imperforate anus, spinal defects), respectively constitute the most benign and severe ends of the bladder exstrophy-epispadias complex (BEEC) spectrum. In 2009, El-Hattab et al. reported the first patient with OEIS complex associated with a chromosome 1p36 deletion. Here we report a second patient with 1p36 deletion who also has classic bladder exstrophy, supporting the possible role of genes in this region in the development of BEEC. The absence of omphalocele and imperforate anus in our patient places him toward classic bladder exstrophy while presence of spina bifida and the absence of coccyx suggest an overlap with OEIS complex. An additional differential diagnosis is the pentalogy of Cantrell in our patient as he also has a diaphragmatic hernia and an incomplete sternum. This is the second observation of a ventral midline birth defect in association with 1p36 deletion syndrome, following El-Hattab et al.'s report [2009]. The three genes (NOCL2, DVL1, and MMP23B) discussed as possible candidates are also among the deleted ones in our patient, supporting the possible role of these genes in BEEC spectrum. © 2016 Wiley Periodicals, Inc.}, } @article {pmid27142332, year = {2016}, author = {Ray, PF and Coutton, C and Arnoult, C}, title = {Sun proteins and Dpy19l2 forming LINC-like links are critical for spermiogenesis.}, journal = {Biology open}, volume = {5}, number = {5}, pages = {535-536}, pmid = {27142332}, issn = {2046-6390}, abstract = {Summary: In this response to Pasch et al.’s (2015) discovery that Sun4 is essential for sperm head formation, the authors highlight that like Sun4, Dpy19l2 has a likely LINK-like function and that it also plays a crucial role in spermiogenesis and male infertility.}, } @article {pmid27138822, year = {2016}, author = {Jung, J and Yi, S}, title = {The case for moderate-risk buyers: An empirical investigation.}, journal = {Psychiatry research}, volume = {240}, number = {}, pages = {300-307}, doi = {10.1016/j.psychres.2016.04.063}, pmid = {27138822}, issn = {1872-7123}, mesh = {Adult ; *Commerce ; Compulsive Behavior/*diagnosis/psychology ; Consumer Behavior/*statistics & numerical data ; Depression/*diagnosis/*psychology ; Depressive Disorder/diagnosis ; Female ; Humans ; *Impulsive Behavior ; Internet/*statistics & numerical data ; Male ; Middle Aged ; *Narcissism ; Pleasure ; Psychiatric Status Rating Scales ; Self Concept ; Social Values ; Surveys and Questionnaires ; }, abstract = {Despite recent increase in research on compulsive buying and excessive buying, the category of buyers whose buying patterns are approaching the clinical level but still somewhat below it has rarely been recognized in the literature. In this paper, we propose the case for the category of moderate-risk buyers. Following Ridgway et al.'s (2008) findings, moderate-risk buyers were operationalized as scoring 21-24 on Compulsive Buying Index. We hypothesized that moderate-risk buyers would hold significantly higher materialistic values than non-compulsive buyers, while exhibiting significantly less depressive symptoms and covert narcissism than full-fledged compulsive buyers. An online survey of individuals who frequently engaged in buying lapses was used (N=809). We found that moderate-risk buyers were significantly different from both compulsive buyers and non-compulsive buyers in the frequency of buying lapses, hiding purchases and frequency of experiencing negative feelings leading to buying lapses. Furthermore, consistent with our hypothesis, moderate-risk buyers held significantly lower covert narcissism and depression than full-fledged compulsive buyers, but their materialism was not significantly different from each other. Our findings support the case for moderate-risk buyers as a separate group from full-fledged compulsive buyers.}, } @article {pmid27117346, year = {2016}, author = {Cottrell, L}, title = {Joy and happiness: a simultaneous and evolutionary concept analysis.}, journal = {Journal of advanced nursing}, volume = {72}, number = {7}, pages = {1506-1517}, doi = {10.1111/jan.12980}, pmid = {27117346}, issn = {1365-2648}, mesh = {Awareness ; *Happiness ; Humans ; Language ; Nurses/*psychology ; *Self-Control ; }, abstract = {AIM: To report a simultaneous and evolutionary analysis of the concepts of joy and long-term happiness.

BACKGROUND: Joy and happiness are underrepresented in the nursing literature, though negative concepts are well represented. When mentioned in the literature, neither joy nor happiness is adequately defined, explained, or clearly understood. To promote further investigation of these concepts in nursing and to explore their relationship with health and healing, conceptual clarity is an essential first step.

DESIGN: Concept analysis.

DATA SOURCES: The following databases were searched, without time restrictions, for articles in English: Academic Search Complete, Anthropology Plus; ATLA Religious Database with ATLASerials; Cumulative Index of Nursing and Allied Health Literature (CINAHL); Education Research Complete; Humanities International Complete; Psych EXTRA; and SocINDEX with Full Text. The final sample size consists of 61 articles and one book, published between 1978-2014.

METHOD: An adapted combination of Rodgers' Evolutionary Model and Haase et al.'s Simultaneous Concept Analysis (SCA) method.

RESULTS: Though both are positive concepts, joy and happiness have significant differences. Attributes of joy describe a spontaneous, sudden and transient concept associated with connection, awareness, and freedom. Attributes of happiness describe a pursued, long-lasting, stable mental state associated with virtue and self-control.

CONCLUSION: Further exploration of joy and happiness is necessary to ascertain their relationship with health and their value to nursing practice and theory development. Nurses are encouraged to consider the value of positive concepts to all areas of nursing.}, } @article {pmid27105643, year = {2016}, author = {Schölmerich, VL and Kawachi, I}, title = {Translating the Social-Ecological Perspective Into Multilevel Interventions for Family Planning: How Far Are We?.}, journal = {Health education & behavior : the official publication of the Society for Public Health Education}, volume = {43}, number = {3}, pages = {246-255}, doi = {10.1177/1090198116629442}, pmid = {27105643}, issn = {1552-6127}, mesh = {Contraception ; *Family Planning Services/methods ; *Health Behavior ; *Health Promotion/methods ; Humans ; Public Health Practice ; Sexual Behavior ; *Social Environment ; Social Theory ; }, abstract = {Scholars and practitioners frequently make recommendations to develop family planning interventions that are "multilevel." Such interventions take explicit account of the role of environments by incorporating multilevel or social-ecological frameworks into their design and implementation. However, research on how interventions have translated these concepts into practice in the field of family planning-and generally in public health-remains scarce. This article seeks to review the current definitions of multilevel interventions and their operationalization in the field of family planning. First, we highlight the divergent definitions of multilevel interventions and show the persistent ambiguity around this term. We argue that interventions involving activities at several levels but lacking targets (i.e., objectives) to create change on more than one level have not incorporated a social-ecological framework and should therefore not be considered as "multilevel." In a second step, we assess the extent to which family planning interventions have successfully incorporated a social-ecological framework. To this end, the 63 studies featured in Mwaikambo et al.'s systematic review on family planning interventions were reexamined. This assessment indicates that the multilevel or social-ecological perspective has seldom been translated into interventions. Specifically, the majority of interventions involved some form of activity at the community and/or organizational level, yet targeted and measured intrapersonal change as opposed to explicitly targeting/measuring environmental modification.}, } @article {pmid27101305, year = {2016}, author = {Lu, Y and Li, L and Zhang, H and Yang, Y}, title = {An Extended Chaotic Maps-Based Three-Party Password-Authenticated Key Agreement with User Anonymity.}, journal = {PloS one}, volume = {11}, number = {4}, pages = {e0153870}, pmid = {27101305}, issn = {1932-6203}, mesh = {*Computer Security ; *Confidentiality ; *Nonlinear Dynamics ; }, abstract = {User anonymity is one of the key security features of an authenticated key agreement especially for communicating messages via an insecure network. Owing to the better properties and higher performance of chaotic theory, the chaotic maps have been introduced into the security schemes, and hence numerous key agreement schemes have been put forward under chaotic-maps. Recently, Xie et al. released an enhanced scheme under Farash et al.'s scheme and claimed their improvements could withstand the security loopholes pointed out in the scheme of Farash et al., i.e., resistance to the off-line password guessing and user impersonation attacks. Nevertheless, through our careful analysis, the improvements were released by Xie et al. still could not solve the problems troubled in Farash et al‥ Besides, Xie et al.'s improvements failed to achieve the user anonymity and the session key security. With the purpose of eliminating the security risks of the scheme of Xie et al., we design an anonymous password-based three-party authenticated key agreement under chaotic maps. Both the formal analysis and the formal security verification using AVISPA are presented. Also, BAN logic is used to show the correctness of the enhancements. Furthermore, we also demonstrate that the design thwarts most of the common attacks. We also make a comparison between the recent chaotic-maps based schemes and our enhancements in terms of performance.}, } @article {pmid27091755, year = {2016}, author = {Wu, L and Zhang, Y and Li, L and Shen, J}, title = {Efficient and Anonymous Authentication Scheme for Wireless Body Area Networks.}, journal = {Journal of medical systems}, volume = {40}, number = {6}, pages = {134}, pmid = {27091755}, issn = {1573-689X}, mesh = {Algorithms ; *Computer Security ; Confidentiality ; Humans ; Monitoring, Ambulatory/*instrumentation ; Telemetry/*methods ; Wireless Technology/*organization & administration ; }, abstract = {As a significant part of the Internet of Things (IoT), Wireless Body Area Network (WBAN) has attract much attention in this years. In WBANs, sensors placed in or around the human body collect the sensitive data of the body and transmit it through an open wireless channel in which the messages may be intercepted, modified, etc. Recently, Wang et al. presented a new anonymous authentication scheme for WBANs and claimed that their scheme can solve the security problems in the previous schemes. Unfortunately, we demonstrate that their scheme cannot withstand impersonation attack. Either an adversary or a malicious legal client could impersonate another legal client to the application provider. In this paper, we give the detailed weakness analysis of Wang et al.'s scheme at first. Then we present a novel anonymous authentication scheme for WBANs and prove that it's secure under a random oracle model. At last, we demonstrate that our presented anonymous authentication scheme for WBANs is more suitable for practical application than Wang et al.'s scheme due to better security and performance. Compared with Wang et al.'s scheme, the computation cost of our scheme in WBANs has reduced by about 31.58%.}, } @article {pmid29367566, year = {2016}, author = {Anderson, RH and Spicer, DE and Mori, S}, title = {Of Tracts, Rings, Nodes, Cusps, Sinuses, and Arrhythmias-A Comment on Szili-Torok et al.'s Paper Entitled "The 'Dead-End Tract' and Its Role in Arrhythmogenesis". J. Cardiovasc. Dev. Dis. 2016, 3, 11.}, journal = {Journal of cardiovascular development and disease}, volume = {3}, number = {2}, pages = {}, pmid = {29367566}, issn = {2308-3425}, abstract = {In the review, now published as part of the special issue devoted to the development of the conduction tissues, de Vries and his colleagues discuss the potential role of the so-called "dead-end tract" as a substrate for arrhythmogenesis [1].[...].}, } @article {pmid27083191, year = {2016}, author = {Miquel, J and Świderski, Z and Feliu, C}, title = {Spermatozoon ultrastructure of Thysanotaenia congolensis (Cyclophyllidea, Anoplocephalidae, Inermicapsiferinae): phylogenetic implications.}, journal = {Parasitology research}, volume = {115}, number = {8}, pages = {3083-3091}, pmid = {27083191}, issn = {1432-1955}, mesh = {Animals ; Axoneme/physiology/*ultrastructure ; Cell Nucleus ; Cestoda/*classification ; Cestode Infections/parasitology ; Intestinal Diseases, Parasitic/*parasitology ; Male ; Microscopy, Electron, Transmission ; Microtubules/physiology ; Phylogeny ; Rats ; Spermatogenesis/physiology ; Spermatozoa/*ultrastructure ; }, abstract = {The mature spermatozoon of Thysanotaenia congolensis, an intestinal parasite of black rat Rattus rattus from Cape Verde, is described by means of transmission electron microscopy. The ultrastructural organization of the sperm cell of T. congolensis follows Levron et al.'s type VII of the Eucestoda. It corresponds to a uniflagellate spermatozoon that presents crested bodies, periaxonemal sheath and intracytoplasmic walls, spiralled cortical microtubules and nucleus spiralled around the axoneme. These characteristics are also present in the spermatozoa of other inermicapsiferines and differ from the characters found in species belonging to the remaining subfamilies of anoplocephalids, namely Anoplocephalinae, Linstowiinae and Thysanosomatinae. Several authors consider the family Anoplocephalidae as a polyphyletic group, and its relationships with the Davaineidae are a matter of controversy. The phylogenetic implications of spermatological ultrastructural features present in inermicapsiferines and in the remaining anoplocephalids are discussed, and the available data on anoplocephalids are compared to similar results in davaineids in order to contribute to a better knowledge of relationships between these cyclophyllidean families.}, } @article {pmid27077700, year = {2016}, author = {Machado, BC and Dias, P and Lima, VS and Campos, J and Gonçalves, S}, title = {Prevalence and correlates of picky eating in preschool-aged children: A population-based study.}, journal = {Eating behaviors}, volume = {22}, number = {}, pages = {16-21}, doi = {10.1016/j.eatbeh.2016.03.035}, pmid = {27077700}, issn = {1873-7358}, mesh = {Child ; Child, Preschool ; Eating/*physiology ; Feeding Behavior/*psychology ; Female ; Food Preferences/*psychology ; Humans ; Infant ; Logistic Models ; Male ; Parents/psychology ; Prevalence ; Socioeconomic Factors ; }, abstract = {OBJECTIVE: The present study, conducted with a population-based preschool children sample, aimed to examine the prevalence rates of picky eating according to the presence of the avoidance or restriction of food intake, searching for picky-eating correlates.

METHODS: 959 children from 1.5 to 6years old were evaluated by their parents and caregivers/teachers. Picky eating was assessed by CBCL 1.5-5 and C-TRF, following Cano et al.'s (2015) procedure.

RESULTS: The prevalence of picky eating was 25.1%. The comparison of the picky-eating group and the non-picky-eating group indicated that picky eating was more common in older children and in children from lower-income families with younger parents. Significant associations were found between picky eating, pregnancy and birth delivery complications. Emotional and behavioral problems were also found to differentiate picky eaters and non-picky eaters using DSM-5-oriented subscales. The results of a binary logistic regression analysis revealed that children with somatic complaints and attention problems were more likely to be picky eaters.

DISCUSSION: Picky eating in preschool children should be considered together with sociodemographic features, pregnancy and delivery issues, and the presence of emotional and behavioral problems. Our results support the possibility that picky eating, as a specific eating pattern, could also be part of a broader pattern of behavioral problems in children.}, } @article {pmid27077257, year = {2016}, author = {Cerna, M and Ferreira, R and Zaror, C and Navarro, P and Sandoval, P}, title = {Dr. Manuel Cerna et al.'s Reply.}, journal = {Cranio : the journal of craniomandibular practice}, volume = {34}, number = {3}, pages = {210-212}, doi = {10.1080/08869634.2015.1114273}, pmid = {27077257}, issn = {2151-0903}, } @article {pmid27064660, year = {2016}, author = {Safavi, MS and Husain, S and Vasishth, S}, title = {Dependency Resolution Difficulty Increases with Distance in Persian Separable Complex Predicates: Evidence for Expectation and Memory-Based Accounts.}, journal = {Frontiers in psychology}, volume = {7}, number = {}, pages = {403}, pmid = {27064660}, issn = {1664-1078}, abstract = {Delaying the appearance of a verb in a noun-verb dependency tends to increase processing difficulty at the verb; one explanation for this locality effect is decay and/or interference of the noun in working memory. Surprisal, an expectation-based account, predicts that delaying the appearance of a verb either renders it no more predictable or more predictable, leading respectively to a prediction of no effect of distance or a facilitation. Recently, Husain et al. (2014) suggested that when the exact identity of the upcoming verb is predictable (strong predictability), increasing argument-verb distance leads to facilitation effects, which is consistent with surprisal; but when the exact identity of the upcoming verb is not predictable (weak predictability), locality effects are seen. We investigated Husain et al.'s proposal using Persian complex predicates (CPs), which consist of a non-verbal element-a noun in the current study-and a verb. In CPs, once the noun has been read, the exact identity of the verb is highly predictable (strong predictability); this was confirmed using a sentence completion study. In two self-paced reading (SPR) and two eye-tracking (ET) experiments, we delayed the appearance of the verb by interposing a relative clause (Experiments 1 and 3) or a long PP (Experiments 2 and 4). We also included a simple Noun-Verb predicate configuration with the same distance manipulation; here, the exact identity of the verb was not predictable (weak predictability). Thus, the design crossed Predictability Strength and Distance. We found that, consistent with surprisal, the verb in the strong predictability conditions was read faster than in the weak predictability conditions. Furthermore, greater verb-argument distance led to slower reading times; strong predictability did not neutralize or attenuate the locality effects. As regards the effect of distance on dependency resolution difficulty, these four experiments present evidence in favor of working memory accounts of argument-verb dependency resolution, and against the surprisal-based expectation account of Levy (2008). However, another expectation-based measure, entropy, which was computed using the offline sentence completion data, predicts reading times in Experiment 1 but not in the other experiments. Because participants tend to produce more ungrammatical continuations in the long-distance condition in Experiment 1, we suggest that forgetting due to memory overload leads to greater entropy at the verb.}, } @article {pmid27048355, year = {2017}, author = {Huang, CT and Chiang, CH and Hung, CY}, title = {Young children with autism spectrum disorders imitate in the context of others' prior intention.}, journal = {Autism : the international journal of research and practice}, volume = {21}, number = {1}, pages = {83-91}, doi = {10.1177/1362361315627135}, pmid = {27048355}, issn = {1461-7005}, mesh = {Autism Spectrum Disorder/*psychology ; Child ; Child Development Disorders, Pervasive/psychology ; Female ; Humans ; *Imitative Behavior ; *Intention ; Male ; Problem Solving ; }, abstract = {Many studies have shown that children with autism spectrum disorder have some understanding of intentions behind others' goal-directed actions on objects. It is not clear whether they understand intentions at a high level of abstraction reliant on the context in which the actions occur. This study tested their understanding of others' prior intentions with typically developing and developmentally delayed children. We replicated Carpenter et al.'s test of the ability to understand prior intentions embedded in the social situation with an additional context of no prior intention. Results showed that when the experimenter's intention was made known before the demonstration, children without autism spectrum disorder performed not only better than the autism spectrum disorder children but also better than themselves when there was no information about prior intention. No between-condition difference was found in the autism spectrum disorder group. It thus appears that children with autism spectrum disorder have difficulty decoupling intentions from the context of the situation. The present findings, together with previous evidence for the intactness of the ability to understand and to imitate goal-directed actions, suggest that asymmetrical imitation performance occurs at different levels of understanding of intention by children with autism spectrum disorder.}, } @article {pmid27039517, year = {2016}, author = {Pearson, DE and Ortega, YK and Eren, Ö and Hierro, JL}, title = {Quantifying "apparent" impact and distinguishing impact from invasiveness in multispecies plant invasions.}, journal = {Ecological applications : a publication of the Ecological Society of America}, volume = {26}, number = {1}, pages = {162-173}, doi = {10.1890/14-2345}, pmid = {27039517}, issn = {1051-0761}, mesh = {*Grassland ; *Introduced Species ; Montana ; Plants/*classification ; }, abstract = {The quantification of invader impacts remains a major hurdle to understanding and managing invasions. Here, we demonstrate a method for quantifying the community-level impact of multiple plant invaders by applying Parker et al.'s (1999) equation (impact = range x local abundance x per capita effect or per unit effect) using data from 620 survey plots from 31 grasslands across west-central Montana, USA. In testing for interactive effects of multiple invaders on native plant abundance (percent cover), we found no evidence for invasional meltdown or synergistic interactions for the 25 exotics tested. While much concern exists regarding impact thresholds, we also found little evidence for nonlinear relationships between invader abundance and impacts. These results suggest that management actions that reduce invader abundance should reduce invader impacts monotonically in this system. Eleven of 25 invaders had significant per unit impacts (negative local-scale relationships between invader and native cover). In decomposing the components of impact, we found that local invader abundance had a significant influence on the likelihood of impact, but range (number of plots occupied) did not. This analysis helped to differentiate measures of invasiveness (local abundance and range) from impact to distinguish high-impact invaders from invaders that exhibit negligible impacts, even when widespread. Distinguishing between high- and low-impact invaders should help refine trait-based prediction of problem species. Despite the unique information derived from evaluation of per unit effects of invaders, invasiveness 'scores based on range and local abundance produced similar rankings to impact scores that incorporated estimates of per unit effects. Hence, information on range and local abundance alone was sufficient to identify problematic plant invaders at the regional scale. In comparing empirical data on invader impacts to the state noxious weed list, we found that the noxious weed list captured 45% of the high impact invaders but missed 55% and assigned the lowest risk category to the highest-impact invader. While such subjective weed lists help to guide invasive species management, empirical data are needed to develop more comprehensive rankings of ecological impacts. Using weed lists to classify invaders for testing invasion theory is not well supported.}, } @article {pmid27034975, year = {2016}, author = {Raja Lakshmi, C and Ayesha Thabusum, D and Bhavana, SM}, title = {An Innovative Approach to Evaluate the Morphological Patterns of Soft Palate in Oral Submucous Fibrosis Patients: A Digital Cephalometric Study.}, journal = {International journal of chronic diseases}, volume = {2016}, number = {}, pages = {5428581}, pmid = {27034975}, issn = {2356-6981}, abstract = {Oral submucous fibrosis (OSMF) is a chronic insidious disease affecting mucosa and submucosa of oral cavity and soft palate. The present study aimed to evaluate the morphology of soft palate in normal individuals and OSMF patients using lateral cephalometry and to compare and correlate these variants of soft palate with different stages of OSMF. 100 subjects were included in the study, who were divided into two groups. Group I included 50 subjects with clinical diagnosis of OSMF and Group II included 50 normal subjects (control group). Using digital lateral cephalometry, velar length and width were measured and soft palatal patterns were categorized based on You et al.'s classification. Leaf and rat-tail patterns of soft palate were predominant in control group, whereas butt and crook shaped variants were more in study group. Anteroposterior (A-P) length of soft palate was significantly greater in stage I OSMF, while superoinferior (S-I) width was greater in stage III OSMF. Interestingly, a negative correlation was observed in staging of OSMF and A-P dimensions. As the staging of OSMF advances, the A-P length of soft palate decreases, but S-I width increases.}, } @article {pmid27031489, year = {2016}, author = {Rosenberg, J}, title = {Approaches to Increasing Ethical Compliance in China with Drug Trial Standards of Practice.}, journal = {Journal of Alzheimer's disease : JAD}, volume = {52}, number = {3}, pages = {825-827}, doi = {10.3233/JAD-151196}, pmid = {27031489}, issn = {1875-8908}, mesh = {Biomedical Research ; China ; Dementia/*drug therapy ; Humans ; Informed Consent/*ethics/standards ; *Publishing ; *Randomized Controlled Trials as Topic/ethics/methods/standards ; }, abstract = {Zeng et al.'s Ethics Review highlights some of the challenges associated with clinical research in China. They found that only a minority of published clinical trials of anti-dementia drugs reported that they fulfilled the basic ethical principles as outlined in the Declaration of Helsinki. With recent reports of scientific misconduct from China, there is an urgent need to find approaches to compel researchers to adhere to ethical research practices. This problem does not call for a simple solution, but if forces are joined with governmental regulations, education in ethics issues for medical researchers, and strong reinforcement by Chinese journal editors not to publish studies with these flaws, then research ethics and publication standards will probably improve. Other solutions to foster ethical practice of drug trials are discussed including Chinese initiatives directed at managing conflict of interest from the pharmaceutical industry and educating clinical researchers.}, } @article {pmid27030682, year = {2016}, author = {Matsumoto, S and Ito, T}, title = {Segmental transition of the first syllables of words in Japanese children who stutter: Comparison between word and sentence production.}, journal = {Clinical linguistics & phonetics}, volume = {30}, number = {7}, pages = {519-530}, doi = {10.3109/02699206.2016.1151937}, pmid = {27030682}, issn = {1464-5076}, mesh = {Asian People ; Child ; Female ; Humans ; *Language ; Male ; Speech Production Measurement/*methods ; Stuttering/*physiopathology ; }, abstract = {Matsumoto-Shimamori, Ito, Fukuda, & Fukuda (2011) proposed the hypothesis that in Japanese, the transition from the core vowels (i.e. syllable nucleus) of the first syllables of words to the following segments affected the occurrence of stuttering. Moreover, in this transition position, an inter-syllabic transition precipitated more stuttering than an intra-syllabic one (Shimamori & Ito, 2007, 2008). However, these studies have only used word production tasks. The purpose of this study was to investigate whether the same results could be obtained in sentence production tasks. Participants were 28 Japanese school-age children who stutter, ranging in age from 7;3 to 12;7. The frequency of stuttering on words with an inter-syllabic transition was significantly higher than on those having an intra-syllabic transition, not only in isolated words but in the first words of sentences. These results suggested that Matsumoto et al.'s hypothesis could be applicable to the results of sentence production tasks.}, } @article {pmid27029105, year = {2016}, author = {Grabbe, JW}, title = {Word Frequency Effects for LEET Lettering in Word Recognition.}, journal = {The American journal of psychology}, volume = {129}, number = {1}, pages = {37-47}, doi = {10.5406/amerjpsyc.129.1.0037}, pmid = {27029105}, issn = {0002-9556}, mesh = {Adult ; Humans ; Pattern Recognition, Visual/*physiology ; Psycholinguistics/*methods ; Psychomotor Performance/*physiology ; *Reading ; Young Adult ; }, abstract = {Letter substitution has been shown to have a cost to word recognition performance, such as increased reaction time. The use of orthographically similar numbers or symbols as a substitute for letters is known as LEET. Perea, Duñabeitia, and Carreiras (2008) showed that word recognition was not affected when LEET substitutions were used as primes. This study examined whether the effects of LEET prime substitutions would remain constant across word frequency. The apparent lack of substitution costs may have been an effect of word-level processing such as holistic bias for high-frequency words. Evidence that LEET does not have an appreciable cost to performance across word frequency suggests that such orthographic substitutions are processed much like normally lettered words, which supported Perea et al.'s findings. It was suggested that LEET substitutions offset substitution costs because of orthography (because of more complete processing of nonsubstituted letters) rather than lexical effects (i.e., holistic bias).}, } @article {pmid27027262, year = {2016}, author = {Koopman, I and Callaghan-Koru, JA and Alaofin, O and Argani, CH and Farzin, A}, title = {Early skin-to-skin contact for healthy full-term infants after vaginal and caesarean delivery: a qualitative study on clinician perspectives.}, journal = {Journal of clinical nursing}, volume = {25}, number = {9-10}, pages = {1367-1376}, doi = {10.1111/jocn.13227}, pmid = {27027262}, issn = {1365-2702}, mesh = {Adult ; *Attitude of Health Personnel ; Baltimore ; Cesarean Section ; Delivery, Obstetric ; Female ; Humans ; Infant, Newborn ; Interviews as Topic ; *Kangaroo-Mother Care Method ; Middle Aged ; *Mother-Child Relations ; Nursing Staff, Hospital/*psychology ; Pregnancy ; Young Adult ; }, abstract = {AIMS AND OBJECTIVES: This study aims to provide insight into key factors from a clinician's perspective that influence uninterrupted early skin-to-skin contact after vaginal and caesarean delivery of healthy full-term infants.

BACKGROUND: Early skin-to-skin contact of healthy full-term infants ideally begins immediately after birth and continues for the first hour or the first breastfeed as recommended by the Baby Friendly Hospital Initiative. However, adoption of early skin-to-skin contact is low in many settings and the barriers that hinder its universal use are not well understood.

DESIGN: An exploratory qualitative research design using semi-structured interviews.

METHODS: Eleven clinicians were interviewed, including five registered nurses and one medical doctor from the obstetrics and gynaecology unit as well as four registered nurses and one medical doctor from the neonatal intensive care unit. Core topics that were discussed included perceptions on early skin-to-skin contact and facilitating factors and barriers to early skin-to-skin contact after vaginal and caesarean delivery. Interview sessions were recorded, transcribed and analysed using a thematic analysis approach. A coding framework was developed from which subthemes emerged. The overall themes were adopted from Lee et al.'s thematic framework to categorise factors into institutional, familial-level and implementation factors.

FINDINGS: Critical institutional factors included inadequate staffing and education of clinicians on early skin-to-skin contact. On a familial level, parental education and motivation were identified as important factors. Barriers to implementation included the absence of a clinical algorithm and unclear definitions for eligible mothers and infants.

CONCLUSIONS: Various facilitating factors and barriers to early skin-to-skin contact of healthy full-term infants born via vaginal and caesarean delivery were identified.

Addressing these factors can help to provide a better understanding of clinician perspectives on early skin-to-skin contact and help guide its implementation as standard of care for healthy full-term infants.}, } @article {pmid27026666, year = {2016}, author = {Hambli, R and Boughattas, MH and Daniel, JL and Kourta, A}, title = {Prediction of denosumab effects on bone remodeling: A combined pharmacokinetics and finite element modeling.}, journal = {Journal of the mechanical behavior of biomedical materials}, volume = {60}, number = {}, pages = {492-504}, doi = {10.1016/j.jmbbm.2016.03.010}, pmid = {27026666}, issn = {1878-0180}, mesh = {Bone Density ; *Bone Remodeling ; Computer Simulation ; Denosumab/pharmacokinetics/*pharmacology ; Femur/physiology ; Finite Element Analysis ; Humans ; Osteoblasts/cytology ; Osteoclasts/cytology ; }, abstract = {Denosumab is a fully human monoclonal antibody that inhibits receptor activator of nuclearfactor-kappa B ligand (RANKL). This key mediator of osteoclast activities has been shown to inhibit osteoclast differentiation and hence, to increase bone mineral density (BMD) in treated patients. In the current study, we develop a computer model to simulate the effects of denosumab treatments (dose and duration) on the proximal femur bone remodeling process quantified by the variation in proximal femur BMD. The simulation model is based on a coupled pharmacokinetics model of denosumab with a pharmacodynamics model consisting of a mechanobiological finite element remodeling model which describes the activities of osteoclasts and osteoblasts. The mechanical behavior of bone is described by taking into account the bone material fatigue damage accumulation and mineralization. A coupled strain-damage stimulus function is proposed which controls the level of bone cell autocrine and paracrine factors. The cellular behavior is based on Komarova et al.׳s (2003) dynamic law which describes the autocrine and paracrine interactions between osteoblasts and osteoclasts and computes cell population dynamics and changes in bone mass at a discrete site of bone remodeling. Therefore, when an external mechanical stress is applied, bone formation and resorption is governed by cell dynamics rather than by adaptive elasticity approaches. The proposed finite element model was implemented in the finite element code Abaqus (UMAT routine). In order to perform a preliminary validation, in vivo human proximal femurs were selected and scanned at two different time intervals (at baseline and at a 36-month interval). Then, a 3D FE model was generated and the denosumab-remodeling algorithm was applied to the scans at t0 simulating daily walking activities for a duration of 36 months. The predicted results (density variation) were compared to existing published ones performed on a human cohort (FREEDOM).}, } @article {pmid27019082, year = {2016}, author = {Oh, SA and Yea, JW and Kang, MK and Park, JW and Kim, SK}, title = {Analysis of the Setup Uncertainty and Margin of the Daily ExacTrac 6D Image Guide System for Patients with Brain Tumors.}, journal = {PloS one}, volume = {11}, number = {3}, pages = {e0151709}, pmid = {27019082}, issn = {1932-6203}, mesh = {Adult ; Aged ; Algorithms ; Brain Neoplasms/pathology/*radiotherapy ; Cone-Beam Computed Tomography ; *Dose Fractionation, Radiation ; Female ; Humans ; Male ; Middle Aged ; Models, Theoretical ; Neoplasm, Residual/diagnosis ; Radiotherapy Planning, Computer-Assisted/*methods ; Radiotherapy, Image-Guided/*methods ; Radiotherapy, Intensity-Modulated/*methods ; Treatment Outcome ; Uncertainty ; }, abstract = {This study evaluated the setup uncertainties for brain sites when using BrainLAB's ExacTrac X-ray 6D system for daily pretreatment to determine the optimal planning target volume (PTV) margin. Between August 2012 and April 2015, 28 patients with brain tumors were treated by daily image-guided radiotherapy using the BrainLAB ExacTrac 6D image guidance system of the Novalis-Tx linear accelerator. DUONTM (Orfit Industries, Wijnegem, Belgium) masks were used to fix the head. The radiotherapy was fractionated into 27-33 treatments. In total, 844 image verifications were performed for 28 patients and used for the analysis. The setup corrections along with the systematic and random errors were analyzed for six degrees of freedom in the translational (lateral, longitudinal, and vertical) and rotational (pitch, roll, and yaw) dimensions. Optimal PTV margins were calculated based on van Herk et al.'s [margin recipe = 2.5∑ + 0.7σ - 3 mm] and Stroom et al.'s [margin recipe = 2∑ + 0.7σ] formulas. The systematic errors (∑) were 0.72, 1.57, and 0.97 mm in the lateral, longitudinal, and vertical translational dimensions, respectively, and 0.72°, 0.87°, and 0.83° in the pitch, roll, and yaw rotational dimensions, respectively. The random errors (σ) were 0.31, 0.46, and 0.54 mm in the lateral, longitudinal, and vertical rotational dimensions, respectively, and 0.28°, 0.24°, and 0.31° in the pitch, roll, and yaw rotational dimensions, respectively. According to van Herk et al.'s and Stroom et al.'s recipes, the recommended lateral PTV margins were 0.97 and 1.66 mm, respectively; the longitudinal margins were 1.26 and 3.47 mm, respectively; and the vertical margins were 0.21 and 2.31 mm, respectively. Therefore, daily setup verifications using the BrainLAB ExacTrac 6D image guide system are very useful for evaluating the setup uncertainties and determining the setup margin.}, } @article {pmid27007910, year = {2016}, author = {Rosati, AG and Warneken, F}, title = {How comparative psychology can shed light on human evolution: Response to Beran et al.'s discussion of "Cognitive capacities for cooking in chimpanzees".}, journal = {Learning & behavior}, volume = {44}, number = {2}, pages = {109-115}, pmid = {27007910}, issn = {1543-4508}, mesh = {Animals ; Cognition ; *Cooking ; *Learning ; Pan troglodytes ; *Psychology, Comparative ; }, abstract = {We recently reported a study (Warneken & Rosati Proceedings of the Royal Society B, 282, 20150229, 2015) examining whether chimpanzees possess several cognitive capacities that are critical to engage in cooking. In a subsequent commentary, Beran, Hopper, de Waal, Sayers, and Brosnan Learning & Behavior (2015) asserted that our paper has several flaws. Their commentary (1) critiques some aspects of our methodology and argues that our work does not constitute evidence that chimpanzees can actually cook; (2) claims that these results are old news, as previous work had already demonstrated that chimpanzees possess most or all of these capacities; and, finally, (3) argues that comparative psychological studies of chimpanzees cannot adequately address questions about human evolution, anyway. However, their critique of the premise of our study simply reiterates several points we made in the original paper. To quote ourselves: "As chimpanzees neither control fire nor cook food in their natural behavior, these experiments therefore focus not on whether chimpanzees can actually cook food, but rather whether they can apply their cognitive skills to novel problems that emulate cooking" (Warneken & Rosati Proceedings of the Royal Society B, 282, 20150229, 2015, p. 2). Furthermore, the methodological issues they raise are standard points about psychological research with animals-many of which were addressed synthetically across our 9 experiments, or else are orthogonal to our claims. Finally, we argue that comparative studies of extant apes (and other nonhuman species) are a powerful and indispensable method for understanding human cognitive evolution.}, } @article {pmid26990803, year = {2017}, author = {Read, R and Moberly, NJ and Salter, D and Broome, MR}, title = {Concepts of Mental Disorders in Trainee Clinical Psychologists.}, journal = {Clinical psychology & psychotherapy}, volume = {24}, number = {2}, pages = {441-450}, doi = {10.1002/cpp.2013}, pmid = {26990803}, issn = {1099-0879}, mesh = {Adult ; *Attitude of Health Personnel ; Female ; Health Personnel/education/*psychology ; Humans ; Male ; *Mental Disorders ; Middle Aged ; Psychotherapy/*education ; Surveys and Questionnaires ; Young Adult ; }, abstract = {BACKGROUND: The models of mental disorders held by all mental health professionals are implicit in their attitudes and inform all aspects of theory and practice. The present study aims to explore the attitudes of trainee clinical psychologists towards mental disorders by building on a study conducted by Harland et al. () with psychiatrists. In so doing, the present study contributes to an evidence base that can inform the development of clinical training programs and multidisciplinary working.

METHODS: The Maudsley Attitude Questionnaire was administered in an online survey of trainee clinical psychologists (n = 289).

RESULTS: Analyses of variance revealed main effects of model, and of diagnostic category, and a significant interaction effect between model and diagnostic category. Principal component analysis revealed a biological-psychosocial continuum and cognitive/behavioural and psychodynamic/spiritual dimensions. Comparisons with Harland et al.'s () psychiatrists revealed large differences, particularly in biological and social constructionist model endorsement.

CONCLUSION: Results suggest that the attitudes of psychologists and psychiatrists continue to sit at opposite ends of a biological-psychosocial continuum. However, an area of consensus regarding psychotherapeutic models was indicated. Training courses can be reassured that strong opinions tended to reflect the evidence base. Future research with similarly large representative samples from different disciplines would allow findings of the current study to be better contextualized. Copyright © 2016 John Wiley & Sons, Ltd.

KEY PRACTITIONER MESSAGE: The models of mental disorders held by clinical psychologists are implicit in their attitudes and inform all aspects of theory and practice. We found that trainee clinical psychologists continue to favour psychosocial over biological understandings of mental disorders, giving the cognitive, behavioural and psychodynamic models equal value overall, and stronger attitudes were supported by the evidence base. We found that trainee clinical psychologists organized their attitudes around a biological-psychosocial continuum and cognitive/behavioural and psychodynamic/spiritual dimensions. These findings may be useful for those involved in developing clinical training programs and multidisciplinary working because they provide an insight into the attitudes of emerging clinical psychologists.}, } @article {pmid26989244, year = {2016}, author = {de Montjoye, YA and Pentland, AS}, title = {Response to Comment on "Unique in the shopping mall: On the reidentifiability of credit card metadata".}, journal = {Science (New York, N.Y.)}, volume = {351}, number = {6279}, pages = {1274}, doi = {10.1126/science.aaf1578}, pmid = {26989244}, issn = {1095-9203}, mesh = {*Commerce ; *Data Collection ; Female ; Humans ; *Information Dissemination ; Male ; *Privacy ; }, abstract = {Sánchez et al.'s textbook k-anonymization example does not prove, or even suggest, that location and other big-data data sets can be anonymized and of general use. The synthetic data set that they "successfully anonymize" bears no resemblance to modern high-dimensional data sets on which their methods fail. Moving forward, deidentification should not be considered a useful basis for policy.}, } @article {pmid26988375, year = {2017}, author = {Ahola, S}, title = {Why (not) disagree? Human values and the readiness to question experts' views.}, journal = {Public understanding of science (Bristol, England)}, volume = {26}, number = {3}, pages = {339-354}, doi = {10.1177/0963662516637818}, pmid = {26988375}, issn = {1361-6609}, mesh = {Adolescent ; Adult ; Aged ; *Dissent and Disputes ; Female ; Finland ; Humans ; Male ; Middle Aged ; *Professional Competence/standards ; *Social Values ; Surveys and Questionnaires ; Young Adult ; }, abstract = {Whether people blindly trust experts on all occasions or whether they evaluate experts' views and question them if necessary is a vital question. This study investigates associations of human values with the readiness to question experts' views and one's reasons for not disagreeing with experts among randomly sampled Finns. Readiness to question experts' views and one's reasons for not disagreeing were inferred from self-reported written accounts. Value priorities were measured with Schwartz et al.'s Portrait Values Questionnaire and Wach and Hammer's items concerning rational and non-rational truth. The results showed that after adjusting for the effects of age, sex and education, the values of power and rational truth were positively associated, whereas the values of security, conformity and tradition were negatively associated with readiness to question experts' views. Furthermore, the analysis indicated that the reasons for not disagreeing with experts were related to individual factors, situational factors, social risks and views about experts.}, } @article {pmid26984493, year = {2016}, author = {Del Giudice, M and Lippa, RA and Puts, DA and Bailey, DH and Bailey, JM and Schmitt, DP}, title = {Joel et al.'s method systematically fails to detect large, consistent sex differences.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {113}, number = {14}, pages = {E1965}, pmid = {26984493}, issn = {1091-6490}, mesh = {Humans ; *Sex Characteristics ; }, } @article {pmid26974122, year = {2016}, author = {Kan, C and Ge, J and Ma, H}, title = {Aluminum methyl, alkoxide and α-alkoxy ester complexes supported by 6,6'-dimethylbiphenyl-bridged salen ligands: synthesis, characterization and catalysis for rac-lactide polymerization.}, journal = {Dalton transactions (Cambridge, England : 2003)}, volume = {45}, number = {15}, pages = {6682-6695}, doi = {10.1039/c5dt04633e}, pmid = {26974122}, issn = {1477-9234}, abstract = {The synthesis and characterization of aluminum alkyl and alkoxide complexes bearing racemic 6,6'-dimethylbiphenyl-bridged salen-type ligands, and their catalysis in the ring-opening polymerization (ROP) of rac-lactide are reported. Reactions of AlMe3 with various amounts of the proligands (6,6'-[(6,6'-dimethyl-[1,1'-biphenyl]-2,2'-diyl)bis(nitrylomethilidyne)]-bis(2-R(1)-4-R(2)-phenol): , R(1) = R(2) = Me; , R(1) = (t)Bu, R(2) = Me; , R(1) = R(2) = cumyl; , R(1) = Br, R(2) = (t)Bu) afforded the corresponding mono- and dinuclear aluminum methyl complexes [AlMe (), Al2Me4 ()]. Aluminum alkoxide complexes AlO(i)Pr (), AlOBn (), and α-alkoxy ester complexes Al(OCMe2CO2Me) (), Al[(S)-OCHMeCO2Me] () were prepared via in situ alcoholysis of the parent aluminum methyl complex with the corresponding alcohols. The molecular structures of mononuclear complexes , dinuclear complex , alkoxide complexes and α-alkoxy ester complexes were established by single-crystal X-ray diffraction studies. Two broad resonances at about 69-70 ppm and 25-41 ppm were observed in the (27)Al NMR spectra of complexes and , indicating the existence of both four- and five-coordinate aluminum centers in solution, which results from the dissociation of one N donor of the salen ligand, accompanied by an association and dissociation equilibrium of the carbonyl group of the α-alkoxy ester ligand to the aluminum center. Complex is also a rare example of an O-lactate model complex that mimics the first insertion of l-LA. All complexes were investigated for the ROP of rac-LA at 110 °C in toluene. The polymerization initiated by complexes in the presence of (i)PrOH showed living features, affording PLAs with narrow molecular weight distributions (PDIs = 1.03-1.05) and 65-73% isotacticities. Particularly, complex showed an "immortal" behavior for the polymerization of rac-LA in the presence of excess alcohol. Compared with the mononuclear counterparts, the tetra-coordinate dinuclear aluminum complexes enabled a few fold boosts in activity, but gave atactic PLAs with broadened PDIs.}, } @article {pmid26968922, year = {2016}, author = {Baumgartner, WA and Baumgartner, AM}, title = {Accounting for disagreements on average cone loss rates in retinitis pigmentosa with a new kinetic model: Its relevance for clinical trials.}, journal = {Medical hypotheses}, volume = {89}, number = {}, pages = {107-114}, doi = {10.1016/j.mehy.2016.02.014}, pmid = {26968922}, issn = {1532-2777}, mesh = {Apoptosis/*physiology ; Cell Survival ; Humans ; Kinetics ; *Models, Neurological ; Retinal Cone Photoreceptor Cells/*pathology/*physiology ; Retinitis Pigmentosa/*pathology/*physiopathology ; }, abstract = {Since 1985, at least nine studies of the average rate of cone loss in retinitis pigmentosa (RP) populations have yielded conflicting average rate constant values (-k), differing by 90-160%. This is surprising, since, except for the first two investigations, the Harvard or Johns Hopkins' protocols used in these studies were identical with respect to: use of the same exponential decline model, calculation of average -k from individual patient k values, monitoring patients over similarly large time frames, and excluding data exhibiting floor and ceiling effects. A detailed analysis of Harvard's and Hopkins' protocols and data revealed two subtle differences: (i) Hopkins' use of half-life t0.5 (or t(1/e)) for expressing patient cone-loss rates rather than k as used by Harvard; (ii) Harvard obtaining substantially more +k from improving fields due to dormant-cone recovery effects and "small -k" values than Hopkins' ("small -k" is defined as less than -0.040 year(-1)), e.g., 16% +k, 31% small -k, vs. Hopkins' 3% and 6% respectively. Since t0.5=0.693/k, it follows that when k=0, or is very small, t0.5 (or t(1/e)) is respectively infinity or a very large number. This unfortunate mathematical property (which also prevents t0.5 (t(1/e)) histogram construction corresponding to -k to +k) caused Hopkins' to delete all "small -k" and all +k due to "strong leverage". Naturally this contributed to Hopkins' larger average -k. Difference (ii) led us to re-evaluate the Harvard/Hopkins' exponential unchanging -k model. In its place we propose a model of increasing biochemical stresses from dying rods on cones during RP progression: increasing oxidative stresses and trophic factor deficiencies (e.g., RdCVF), and RPE malfunction. Our kinetic analysis showed rod loss to follow exponential kinetics with unchanging -k due to constant genetic stresses, thereby providing a theoretical basis for Clarke et al.'s empirical observation of such kinetics with eleven animal models of RP. In contrast to this, we show that cone loss occurs in patients with increasing -k values during RP progression. And as the Hopkins' protocol selects more advanced RP cases than Harvard's to assure avoidance of ceiling effects (Harvard does this by kinetic monitoring), we show increasing -k kinetics to be the reason Harvard obtains more +k and small -k values. Thus the combined effects of (i) and (ii) produce Harvard's smaller average -k value. The relevance of the increasing biochemical stress model for optimizing clinical trials is discussed.}, } @article {pmid26962711, year = {2016}, author = {Dexter, F and Masursky, D and Szeluga, D and Hindman, BJ}, title = {Work Habits Are Valid Components of Evaluations of Anesthesia Residents Based on Faculty Anesthesiologists' Daily Written Comments About Residents.}, journal = {Anesthesia and analgesia}, volume = {122}, number = {5}, pages = {1625-1633}, doi = {10.1213/ANE.0000000000001199}, pmid = {26962711}, issn = {1526-7598}, mesh = {Anesthesiology/*education ; *Attitude of Health Personnel ; Clinical Competence ; Education, Medical, Graduate/*methods ; Educational Measurement ; Employee Performance Appraisal/*methods ; *Faculty, Medical ; *Habits ; Humans ; *Internship and Residency ; Surveys and Questionnaires ; Task Performance and Analysis ; *Work Performance ; *Writing ; }, abstract = {BACKGROUND: In our department, faculty anesthesiologists routinely evaluate the resident physicians with whom they worked in an operative setting the day before, providing numerical scores to questions. The faculty can also enter a written comment if so desired. Because residents' work habits are important to anesthesiology program directors, and work habits can improve with feedback, we hypothesized that faculty comments would include the theme of the anesthesia resident's work habits.

METHODS: We analyzed all 6692 faculty comments from January 1, 2011, to June 30, 2015. We quantified use of the theme of Dannefer et al.'s work habit scale, specifically the words and phrases in the scale, and synonyms to the words.

RESULTS: Approximately half (50.7% [lower 99.99% confidence limit, 48.4%]) of faculty comments contained the theme of work habits. Multiple sensitivity analyses were performed excluding individual faculty, residents, and words. The lower confidence limits for comments containing the theme were each >42.7%.

CONCLUSIONS: Although faculty anesthesiologists completed (numerical) questions based on the American College of Graduate Medical Education competencies to evaluate residents, an important percentage of written comments included the theme of work habits. The implication is that the theme has validity as one component of the routine evaluation of anesthesia residents.}, } @article {pmid26960441, year = {2016}, author = {Logačev, P and Vasishth, S}, title = {Understanding underspecification: A comparison of two computational implementations.}, journal = {Quarterly journal of experimental psychology (2006)}, volume = {69}, number = {5}, pages = {996-1012}, pmid = {26960441}, issn = {1747-0226}, mesh = {Comprehension/*physiology ; *Computer Simulation ; Humans ; *Individuality ; *Language ; *Models, Psychological ; *Reading ; }, abstract = {Swets et al. (2008. Underspecification of syntactic ambiguities: Evidence from self-paced reading. Memory and Cognition, 36(1), 201-216) presented evidence that the so-called ambiguity advantage [Traxler et al. (1998). Adjunct attachment is not a form of lexical ambiguity resolution. Journal of Memory and Language, 39(4), 558-592], which has been explained in terms of the Unrestricted Race Model, can equally well be explained by assuming underspecification in ambiguous conditions driven by task-demands. Specifically, if comprehension questions require that ambiguities be resolved, the parser tends to make an attachment: when questions are about superficial aspects of the target sentence, readers tend to pursue an underspecification strategy. It is reasonable to assume that individual differences in strategy will play a significant role in the application of such strategies, so that studying average behaviour may not be informative. In order to study the predictions of the good-enough processing theory, we implemented two versions of underspecification: the partial specification model (PSM), which is an implementation of the Swets et al. proposal, and a more parsimonious version, the non-specification model (NSM). We evaluate the relative fit of these two kinds of underspecification to Swets et al.'s data; as a baseline, we also fitted three models that assume no underspecification. We find that a model without underspecification provides a somewhat better fit than both underspecification models, while the NSM model provides a better fit than the PSM. We interpret the results as lack of unambiguous evidence in favour of underspecification; however, given that there is considerable existing evidence for good-enough processing in the literature, it is reasonable to assume that some underspecification might occur. Under this assumption, the results can be interpreted as tentative evidence for NSM over PSM. More generally, our work provides a method for choosing between models of real-time processes in sentence comprehension that make qualitative predictions about the relationship between several dependent variables. We believe that sentence processing research will greatly benefit from a wider use of such methods.}, } @article {pmid26960114, year = {2016}, author = {Shkalim, E and Ben-Porath, YS and Almagor, M}, title = {Mapping the MMPI-2/MMPI-2-RF Restructured Clinical Scales Onto Mood Markers in an Israeli Sample.}, journal = {Journal of personality assessment}, volume = {98}, number = {4}, pages = {430-434}, doi = {10.1080/00223891.2016.1146291}, pmid = {26960114}, issn = {1532-7752}, mesh = {Adult ; *Affect ; Antisocial Personality Disorder/*diagnosis ; Checklist ; Cross-Cultural Comparison ; Female ; Humans ; Israel ; MMPI/*standards ; Male ; Middle Aged ; Personality/*classification ; Reference Values ; }, abstract = {This study cross-culturally evaluated the Minnesota Multiphasic Personality Inventory-2/MMPI-2 Restructured Form (MMPI-2/MMPI-2-RF) emotion-focused Restructured Clinical (RC) Scales to examine whether their patterns of associations with positive affect (PA) and negative affect (NA) are as expected based on Tellegen, Watson, and Clark's (1999a , 1999b) mood model. The sample was composed of 100 men and 133 women from psychiatric settings in Israel who completed the MMPI-2 and the Mood Check List (MCL; Zevon & Tellegen, 1982). Results indicated that RCd was substantially correlated with both PA and NA in opposite directions, and that RC2 and RC7 were more highly correlated with PA and NA, respectively. Further, when compared with their Clinical Scale counterparts, RC2 and RC7 exhibited comparable convergent validities and improved discriminant properties. Findings provide support for Tellegen et al.'s (2003) goal to link the RC scales to contemporary conceptualizations of mood.}, } @article {pmid26948754, year = {2016}, author = {Costello, FJ}, title = {Monotheism versus an innate bias towards mentalizing.}, journal = {The Behavioral and brain sciences}, volume = {39}, number = {}, pages = {e9}, doi = {10.1017/S0140525X15000394}, pmid = {26948754}, issn = {1469-1825}, mesh = {Humans ; *Religion ; *Theory of Mind ; }, abstract = {Norenzayan et al.'s account for the spread of monotheistic "Big God" religions sees these religions originating as by-products of innate cognitive biases. These biases produce polytheistic rather than monotheistic systems, however, and so do not explain the origin of monotheism. Accounts where monotheism arises from polytheism (for political reasons, for example) appear better able to explain the spread of monotheism.}, } @article {pmid26948746, year = {2016}, author = {White, C and Sousa, P and Prochownik, K}, title = {Explaining the success of karmic religions.}, journal = {The Behavioral and brain sciences}, volume = {39}, number = {}, pages = {e28}, doi = {10.1017/S0140525X15000588}, pmid = {26948746}, issn = {1469-1825}, mesh = {*Cultural Evolution ; Humans ; *Religion ; Social Behavior ; }, abstract = {One of the central claims of Norenzayan et al.'s article is that supernatural monitoring and intergroup competition have facilitated the rise of large-scale prosocial religions. Although the authors outline in detail how social instincts that govern supernatural monitoring are honed by cultural evolution and have given rise to Big Gods, they do not provide a clear explanation for the success of karmic religions. Therefore, to test the real scope of their model, Norenzayan et al. need to seriously engage with questions concerning the evolution of karmic prosocial religions.}, } @article {pmid26948745, year = {2016}, author = {Watts, J and Bulbulia, J and Gray, RD and Atkinson, QD}, title = {Clarity and causality needed in claims about Big Gods.}, journal = {The Behavioral and brain sciences}, volume = {39}, number = {}, pages = {e27}, doi = {10.1017/S0140525X15000576}, pmid = {26948745}, issn = {1469-1825}, mesh = {*Biological Evolution ; *Religion ; }, abstract = {We welcome Norenzayan et al.'s claim that the prosocial effects of beliefs in supernatural agents extend beyond Big Gods. To date, however, supporting evidence has focused on the Abrahamic Big God, making generalisations difficult. We discuss a recent study that highlights the need for clarity about the causal path by which supernatural beliefs affect the evolution of big societies.}, } @article {pmid26948735, year = {2016}, author = {Lindeman, M and Svedholm-Häkkinen, AM}, title = {Let us be careful with the evidence on mentalizing, cognitive biases, and religious beliefs.}, journal = {The Behavioral and brain sciences}, volume = {39}, number = {}, pages = {e18}, doi = {10.1017/S0140525X15000485}, pmid = {26948735}, issn = {1469-1825}, mesh = {Bias ; Cognition ; Compulsive Behavior ; *Religion ; *Theory of Mind ; }, abstract = {Norenzayan et al.'s theoretical synthesis is highly plausible and commendable. However, the empirical evidence for the arguments on mentalizing, cognitive biases, and religious belief is currently not as strong as the writers suggest. Although certainly abundant and compelling, this evidence is indirect, contradictory, and weak and must be acknowledged as such. More direct studies are needed to support the theory.}, } @article {pmid26938307, year = {2016}, author = {Hauptmann, E}, title = {"PROPAGANDISTS FOR THE BEHAVIORAL SCIENCES": THE OVERLOOKED PARTNERSHIP BETWEEN THE CARNEGIE CORPORATION AND SSRC IN THE MID-TWENTIETH CENTURY.}, journal = {Journal of the history of the behavioral sciences}, volume = {52}, number = {2}, pages = {167-187}, doi = {10.1002/jhbs.21786}, pmid = {26938307}, issn = {1520-6696}, mesh = {Behavioral Research/history ; Behavioral Sciences/*history ; Foundations/history ; History, 20th Century ; Humans ; Interinstitutional Relations ; Social Sciences/history ; United States ; }, abstract = {The Carnegie Corporation's role as a patron of the behavioral sciences has been overlooked; its support for the behavioral sciences not only began earlier than the Ford Foundation's but was also at least equally important to their success. I show how the close postwar collaboration between the Carnegie Corporation and the Social Science Research Council (SSRC) to promote the behavioral sciences emerged after a struggle between Carnegie and the Rockefeller Foundation over the direction and leadership of the SSRC. I then focus on three postwar projects Carnegie helped conceive and fund that were publicized as the work of the SSRC: Chase's The Proper Study of Mankind (1948), Stouffer et al.'s The American Soldier (), and the Michigan's Survey Research Center 1952 election study. In each of these projects, Carnegie deliberately muted its own role and promoted the remade SSRC as a major advocate for the behavioral sciences.}, } @article {pmid26931530, year = {2017}, author = {Clark-Polner, E and Johnson, TD and Barrett, LF}, title = {Multivoxel Pattern Analysis Does Not Provide Evidence to Support the Existence of Basic Emotions.}, journal = {Cerebral cortex (New York, N.Y. : 1991)}, volume = {27}, number = {3}, pages = {1944-1948}, pmid = {26931530}, issn = {1460-2199}, mesh = {*Emotions ; Facial Expression ; *Fear ; Humans ; Thinking ; }, abstract = {Saarimaki et al. (2015) published a paper claiming to find the neural "fingerprints" for anger, fear, disgust, happiness, sadness, and surprise using multivariate pattern analysis. There are 2 ways in which Saarimaki et al.'s interpretation mischaracterizes their actual findings. The first is statistical: a pattern that successfully distinguishes the members of one category from the members of another (with an accuracy greater than that which might be expected by chance) is not a "fingerprint" (i.e., an essence); it is an abstract, statistical summary of a variable population of instances. The second way in which Saarimaki et al.'s interpretation mischaracterizes their results is conceptual: their findings do not actually meet the specific criteria for basic emotion theory. Instead, their findings are more consistent with a theory of constructed emotion. In our view, Saarimaki et al. is elegant in method and important in that it demonstrates empirical support for a theory of emotion that relies on population thinking; it is also an example of how essentialism-the belief that all instances of a category possesses necessary features that define what is, and what is not, a category member-contributes to a fundamental misunderstanding of the neural basis of emotion.}, } @article {pmid26909752, year = {2016}, author = {Yang, G and Liu, D and Wang, J and Xie, MG}, title = {Meta-analysis framework for exact inferences with application to the analysis of rare events.}, journal = {Biometrics}, volume = {72}, number = {4}, pages = {1378-1386}, doi = {10.1111/biom.12497}, pmid = {26909752}, issn = {1541-0420}, mesh = {Biometry/methods ; Computer Simulation ; Confidence Intervals ; Humans ; Hypoglycemic Agents/adverse effects ; *Meta-Analysis as Topic ; }, abstract = {The usefulness of meta-analysis has been recognized in the evaluation of drug safety, as a single trial usually yields few adverse events and offers limited information. For rare events, conventional meta-analysis methods may yield an invalid inference, as they often rely on large sample theories and require empirical corrections for zero events. These problems motivate research in developing exact methods, including Tian et al.'s method of combining confidence intervals (2009, Biostatistics, 10, 275-281) and Liu et al.'s method of combining p-value functions (2014, JASA, 109, 1450-1465). This article shows that these two exact methods can be unified under the framework of combining confidence distributions (CDs). Furthermore, we show that the CD method generalizes Tian et al.'s method in several aspects. Given that the CD framework also subsumes the Mantel-Haenszel and Peto methods, we conclude that the CD method offers a general framework for meta-analysis of rare events. We illustrate the CD framework using two real data sets collected for the safety analysis of diabetes drugs.}, } @article {pmid26906685, year = {2016}, author = {Scarpino, M and Lolli, F and Carrai, R and Lanzo, G and Spalletti, M and Barilaro, A and Fattapposta, F and Amantini, A and Grippo, A}, title = {Diagnostic accuracy of neurophysiological criteria for early diagnosis of AIDP: A prospective study.}, journal = {Neurophysiologie clinique = Clinical neurophysiology}, volume = {46}, number = {1}, pages = {35-42}, doi = {10.1016/j.neucli.2015.12.008}, pmid = {26906685}, issn = {1769-7131}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Early Diagnosis ; *Electrodiagnosis ; Female ; Guillain-Barre Syndrome/*diagnosis/*physiopathology ; Humans ; Male ; Middle Aged ; Neural Conduction ; Prospective Studies ; Sensitivity and Specificity ; Young Adult ; }, abstract = {OBJECTIVE: To assess the diagnostic accuracy of electrodiagnostic (EDX) criteria for the early detection and characterization of Guillain-Barré syndrome (GBS) in clinical practice.

METHODS: We conducted a prospective study in patients referred for an EDX exam with clinical suspicion of GBS. We evaluated four sets of neurophysiological criteria and four neurophysiological tests among those recently proposed for the early diagnosis of GBS.

RESULTS: We recruited 84 patients. Acute inflammatory demyelinating polyneuropathy (AIDP) was the final diagnosis in 23 patients. No axonal forms were found. The best sensitivity was obtained using Rajabally et al.'s criteria (82.1%), whereas the specificity was 90.0% for Ho et al.'s and Hadden et al.'s criteria and 100% for the Dutch GBS study group and Rajabally's criteria. Regarding the neurophysiological tests proposed for early diagnosis, the sensitivity ranged from 16.6 to 100%, whereas specificity ranged from 73.1 to 98.3%.

CONCLUSION: The Dutch GBS study group and Rajabally et al.'s criteria showed an optimal combination of sensitivity and specificity for clinical practice, although with a slightly higher sensitivity for Rajabally et al.'s criteria. None of the neurophysiological parameters recently proposed for early diagnosis have good diagnostic accuracy for clinical application.

SIGNIFICANCE: In a real clinical setting with patients referred by neurologists and emergency doctors, an EDX study performed within a week of symptom onset supports the diagnosis of AIDP in 82% of cases.}, } @article {pmid26899744, year = {2016}, author = {Weisleder, P}, title = {It Is Time to Leave the Wilderness: A Commentary on Valencia et al.'s "Program Director Survey: Attitudes Regarding Child Neurology Training".}, journal = {Pediatric neurology}, volume = {57}, number = {}, pages = {3-4}, doi = {10.1016/j.pediatrneurol.2016.01.017}, pmid = {26899744}, issn = {1873-5150}, mesh = {Attitude ; Humans ; Internship and Residency ; Neurology/*education ; Surveys and Questionnaires ; *Wilderness ; }, } @article {pmid26887452, year = {2016}, author = {Vera, JA and Martínez-Sánchez, F}, title = {Ethics, Science and Mind Control: J. M. Rodríguez-Delgado's Legacy.}, journal = {The Spanish journal of psychology}, volume = {19}, number = {}, pages = {E1}, doi = {10.1017/sjp.2016.2}, pmid = {26887452}, issn = {1988-2904}, mesh = {Animals ; *Bibliometrics ; Brain/*physiology ; *Electric Stimulation ; History, 20th Century ; History, 21st Century ; Humans ; Neurophysiology/ethics/*history ; }, abstract = {This work analyses the evolution of the scientific visibility of the neurophysiologist José Manuel Rodríguez Delgado. It examines the longitudinal evolution from 1955 to 2013 of an article (Delgado, Roberts, & Miller, 1954) studying the neurological basis of learning and motivation and compares it with a coetaneous article (Olds & Milner, 1954) with a similar subject and methodology. Both studies have been essential in Psychology. This work analyses the number of times each article has been cited between 1955-1984 and 1985-2013. The results show that the visibility of James Olds and Peter Milner's article (expressed in number of citations between 1955-1984 and 1985-2013) has longitudinally increased (p < .001), whereas the number of citations received by José Manuel Rodríguez Delgado et al.'s article has significantly reduced (p < .001). The results are discussed and the low visibility of Delgado's article is explained through historical and social factors, including the growing concern about compliance with bioethical and research guidelines and the controversial media projection of the Spanish scientist, not by the intrinsic value or the scientific repercussion of the compared articles.}, } @article {pmid26884468, year = {2017}, author = {Carter, AJ and Hollin, CR and Stefanska, EB and Higgs, T and Bloomfield, S}, title = {The Use of Crime Scene and Demographic Information in the Identification of Non-Serial Sexual Homicide.}, journal = {International journal of offender therapy and comparative criminology}, volume = {61}, number = {14}, pages = {1554-1569}, doi = {10.1177/0306624X16630313}, pmid = {26884468}, issn = {1552-6933}, mesh = {Adolescent ; Adult ; Crime Victims/*statistics & numerical data ; England ; Female ; Forensic Psychiatry ; *Homicide ; Humans ; Male ; Matched-Pair Analysis ; Middle Aged ; *Sex Offenses ; Wales ; Weapons/statistics & numerical data ; Wounds and Injuries/epidemiology ; Young Adult ; }, abstract = {As with other sexual offenders, sexual homicide perpetrators can be reluctant to talk about their criminal behavior. Therefore, in homicide cases, forensic practitioners frequently rely on crime scene information to identify any sexual behavior associated with the offense. This study aims to identify objective and readily available crime scene information, alongside information about victims and perpetrators, based on 65 cases from England and Wales in the United Kingdom of men convicted of homicide who had committed a non-serial sexual homicide and 64 cases of men convicted of homicide where the available evidence indicated that it was a non-serial non-sexual homicide. Chi-square tests and logistic regression were used to analyze the data. There were few differences in terms of demographic information and criminal histories between the two perpetrator groups. There were crime scene indicators supporting the use of Ressler et al.'s definition of sexual homicide. The victims of sexual homicide were generally found in their home with the lower half of the body exposed and with evidence of vaginal sex. Furthermore, extreme injuries and strangulation were more frequent in sexual homicides. Use of weapon was associated with a non-sexual homicide. Victims of sexual homicide were as likely to know the perpetrator as not. Potential benefits of the characteristics reported to investigators and forensic practitioners tasked with identifying sexual homicides are discussed and areas for further research suggested.}, } @article {pmid29910259, year = {2016}, author = {Bryant, ES and Duncan, MJ and Birch, SL and James, RS}, title = {Can Fundamental Movement Skill Mastery Be Increased via a Six Week Physical Activity Intervention to Have Positive Effects on Physical Activity and Physical Self-Perception?.}, journal = {Sports (Basel, Switzerland)}, volume = {4}, number = {1}, pages = {}, pmid = {29910259}, issn = {2075-4663}, abstract = {BACKGROUND: Previous research has suggested a positive relationship between fundamental movement skills (FMS) mastery and physical activity (PA) level. Research conducted on interventions to improve FMS mastery is equivocal and further research is needed.

METHODS: An intervention group of 82 children (35 boys and 47 girls) and a control group of 83 children (42 boys and 41 girls) were recruited from Years 4 and 5 (mean age ± SD = 8.3 ± 0.4 years) of two schools in Central England. The intervention included a combination of circuits and dancing to music. Pre and post intervention tests were conducted. Tests included: subjective assessment of eight FMS; objective measurement of two FMS; four day pedometer step count recording; height and mass for Body Mass Index (BMI); and the completion of Harter et al.'s (1982) self-perception questionnaire.

RESULTS: Following a two (pre to post) by two (intervention and control group) mixed-model ANOVA it was highlighted that the intervention group improved mastery in all eight FMS, and increased both daily steps and physical self-perception.

CONCLUSIONS: It can be concluded that focussing one Physical Education (PE) lesson per week on the development of FMS has had a positive benefit on FMS, PA level and physical self-perception for the children in this study.}, } @article {pmid26877131, year = {2016}, author = {Ladouceur, CD}, title = {The error-related negativity: A transdiagnostic marker of sustained threat?.}, journal = {Psychophysiology}, volume = {53}, number = {3}, pages = {389-392}, doi = {10.1111/psyp.12585}, pmid = {26877131}, issn = {1469-8986}, support = {P50 MH080215/MH/NIMH NIH HHS/United States ; }, mesh = {Humans ; Mental Disorders/*diagnosis ; *National Institute of Mental Health (U.S.) ; Phenotype ; Research Design ; }, abstract = {The creation of the National Institute of Mental Health (NIMH) Research Domain Criteria (RDoC) project has been the driving force behind the reconceptualization of the pathogenesis of psychiatric disorders. In this commentary, I explore whether the error-related negativity can be considered as a transdiagnostic marker of sustained threat based on findings from Weinberg, Meyer et al.'s (2016) study in relation to current findings in the literature. Potential alternative study designs, use of a multimodal approach to the assessment of a specific phenotype of clinical phenomenon, and the importance of integrating a neurodevelopmental perspective are also discussed.}, } @article {pmid26877121, year = {2016}, author = {Shankman, SA and Katz, AC and Langenecker, SA}, title = {Taking an RDoC lens to the study of panic disorder: A commentary on Hamm et al. and other thoughts on RDoC.}, journal = {Psychophysiology}, volume = {53}, number = {3}, pages = {328-331}, pmid = {26877121}, issn = {1469-8986}, support = {R01 MH098093/MH/NIMH NIH HHS/United States ; R01 MH101487/MH/NIMH NIH HHS/United States ; }, mesh = {Animals ; Humans ; *National Institute of Mental Health (U.S.) ; *Panic Disorder ; Research ; Thinking ; }, abstract = {The Research Domain Criteria (RDoC) initiative put forth by the National Institute of Mental Health represents an exciting new framework in which to study psychopathology. The article by Hamm et al. (2016) is an interesting application of an "RDoC lens" toward a program of research on panic disorder. This commentary highlights the many strengths of the Hamm et al. (2016) study-most notably the article's application of a well-studied animal model of anxiety (Fanselow's, , threat imminence model) to humans, utilization of an interesting behavioral paradigm (as an analog for avoidance behaviors in panic disorder), and using RDoC to examine predictors of treatment response. This commentary also discusses several questions about RDoC that arise out of Hamm et al. For example, (a) How should participants be selected for RDoC studies? (b) Are RDoC constructs risk factors (and risk factors for what)? (c) Besides Hamm et al.'s, approach, how else can RDoC be used in treatment studies? In sum, Hamm et al. is a very good example of an RDoC study, and in this early phase of the initiative, more examples for how the approach plays out are needed.}, } @article {pmid26866606, year = {2016}, author = {Wang, C and Zhang, X and Zheng, Z}, title = {Cryptanalysis and Improvement of a Biometric-Based Multi-Server Authentication and Key Agreement Scheme.}, journal = {PloS one}, volume = {11}, number = {2}, pages = {e0149173}, pmid = {26866606}, issn = {1932-6203}, mesh = {Algorithms ; Biometric Identification/*methods ; Communication ; *Computer Security ; Confidentiality ; Fuzzy Logic ; Humans ; Information Systems ; Internet ; }, abstract = {With the security requirements of networks, biometrics authenticated schemes which are applied in the multi-server environment come to be more crucial and widely deployed. In this paper, we propose a novel biometric-based multi-server authentication and key agreement scheme which is based on the cryptanalysis of Mishra et al.'s scheme. The informal and formal security analysis of our scheme are given, which demonstrate that our scheme satisfies the desirable security requirements. The presented scheme provides a variety of significant functionalities, in which some features are not considered in the most of existing authentication schemes, such as, user revocation or re-registration and biometric information protection. Compared with several related schemes, our scheme has more secure properties and lower computation cost. It is obviously more appropriate for practical applications in the remote distributed networks.}, } @article {pmid26864871, year = {2016}, author = {Veale, JF}, title = {Factorial Validity and Invariance Assessment of a Short Version of the Recalled Childhood Gender Identity/Role Questionnaire.}, journal = {Archives of sexual behavior}, volume = {45}, number = {3}, pages = {537-550}, doi = {10.1007/s10508-015-0684-0}, pmid = {26864871}, issn = {1573-2800}, mesh = {Adult ; Biomedical Research ; Child ; Child, Preschool ; Factor Analysis, Statistical ; Female ; *Gender Identity ; Humans ; Infant ; Male ; Mental Health ; *Mental Recall ; Psychometrics/statistics & numerical data ; Reproducibility of Results ; Substance-Related Disorders ; Surveys and Questionnaires/standards ; }, abstract = {Recalled childhood gender role/identity is a construct that is related to sexual orientation, abuse, and psychological health. The purpose of this study was to assess the factorial validity of a short version of Zucker et al.'s (2006) "Recalled Childhood Gender Identity/Gender Role Questionnaire" using confirmatory factor analysis and to test the stability of the factor structure across groups (measurement invariance). Six items of the questionnaire were completed online by 1929 participants from a variety of gender identity and sexual orientation groups. Models of the six items loading onto one factor had poor fit for the data. Items were removed for having a large proportion of error variance. Among birth-assigned females, a five-item model had good fit for the data, but there was evidence for differences in scale's factor structure across gender identity, age, level of education, and country groups. Among birth-assigned males, the resulting four-item model did not account for all of the relationship between variables, and modeling for this resulted in a model that was almost saturated. This model also had evidence of measurement variance across gender identity and sexual orientation groups. The models had good reliability and factor score determinacy. These findings suggest that results of previous studies that have assessed recalled childhood gender role/identity may have been susceptible to construct bias due to measurement variance across these groups. Future studies should assess measurement invariance between groups they are comparing, and if it is not found the issue can be addressed by removing variant indicators and/or applying a partial invariance model.}, } @article {pmid26863664, year = {2017}, author = {Yang, Y and Pintus, R and Rushmeier, H and Ivrissimtzis, I}, title = {A 3D Steganalytic Algorithm and Steganalysis-Resistant Watermarking.}, journal = {IEEE transactions on visualization and computer graphics}, volume = {23}, number = {2}, pages = {1002-1013}, doi = {10.1109/TVCG.2016.2525771}, pmid = {26863664}, issn = {1941-0506}, abstract = {We propose a simple yet efficient steganalytic algorithm for watermarks embedded by two state-of-the-art 3D watermarking algorithms by Cho et al. The main observation is that while in a clean model the means/variances of Cho et al.'s normalized histogram bins are expected to follow a Gaussian distribution, in a marked model their distribution will be bimodal. The proposed algorithm estimates the number of bins through an exhaustive search and then the presence of a watermark is decided by a tailor made normality test or a t-test. We also propose a modification of Cho et al.'s watermarking algorithms with the watermark embedded by changing the histogram of the radial coordinates of the vertices. Rather than targeting a continuous statistics such as the mean or variance of the values in a bin, the proposed watermarking modifies a discrete statistic, which here is the height of the histogram bin, to achieve watermark embedding. Experimental results demonstrate that the modified algorithm offers not only better resistance against the steganalytic attack we developed, but also an improved robustness/capacity trade-off.}, } @article {pmid26858621, year = {2016}, author = {Harrison, NR and Ziessler, M}, title = {Effect Anticipation Affects Perceptual, Cognitive, and Motor Phases of Response Preparation: Evidence from an Event-Related Potential (ERP) Study.}, journal = {Frontiers in human neuroscience}, volume = {10}, number = {}, pages = {5}, pmid = {26858621}, issn = {1662-5161}, abstract = {The anticipation of action effects is a basic process that can be observed even for key-pressing responses in a stimulus-response paradigm. In Ziessler et al.'s (2012) experiments participants first learned arbitrary effects of key-pressing responses. In the test phase an imperative stimulus determined the response, but participants withheld the response until a Go-stimulus appeared. Reaction times (RTs) were shorter if the Go-stimulus was compatible with the learned response effect. This is strong evidence that effect representations were activated during response planning. Here, we repeated the experiment using event-related potentials (ERPs), and we found that Go-stimulus locked ERPs depended on the compatibility relationship between the Go-stimulus and the response effect. In general, this supports the interpretation of the behavioral data. More specifically, differences in the ERPs between compatible and incompatible Go-stimuli were found for the early perceptual P1 component and the later frontal P2 component. P1 differences were found only in the second half of the experiment and for long stimulus onset asynchronies (SOAs) between imperative stimulus and Go-stimulus, i.e., when the effect was fully anticipated and the perceptual system was prepared for the effect-compatible Go-stimulus. P2 amplitudes, likely associated with evaluation and conflict detection, were larger when Go-stimulus and effect were incompatible; presumably, incompatibility increased the difficulty of effect anticipation. Onset of response-locked lateralized readiness potentials (R-LRPs) occurred earlier under incompatible conditions indicating extended motor processing. Together, these results strongly suggest that effect anticipation affects all (i.e., perceptual, cognitive, and motor) phases of response preparation.}, } @article {pmid26858197, year = {2016}, author = {Schuergers, N and Lenn, T and Kampmann, R and Meissner, MV and Esteves, T and Temerinac-Ott, M and Korvink, JG and Lowe, AR and Mullineaux, CW and Wilde, A}, title = {Cyanobacteria use micro-optics to sense light direction.}, journal = {eLife}, volume = {5}, number = {}, pages = {}, pmid = {26858197}, issn = {2050-084X}, support = {MR/K015826/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {*Light ; *Locomotion ; Synechocystis/*physiology/*radiation effects ; }, abstract = {Bacterial phototaxis was first recognized over a century ago, but the method by which such small cells can sense the direction of illumination has remained puzzling. The unicellular cyanobacterium Synechocystis sp. PCC 6803 moves with Type IV pili and measures light intensity and color with a range of photoreceptors. Here, we show that individual Synechocystis cells do not respond to a spatiotemporal gradient in light intensity, but rather they directly and accurately sense the position of a light source. We show that directional light sensing is possible because Synechocystis cells act as spherical microlenses, allowing the cell to see a light source and move towards it. A high-resolution image of the light source is focused on the edge of the cell opposite to the source, triggering movement away from the focused spot. Spherical cyanobacteria are probably the world's smallest and oldest example of a camera eye.}, } @article {pmid26854153, year = {2015}, author = {Jason, LA and Sunnquist, M and Kot, B and Brown, A}, title = {Unintended Consequences of not Specifying Exclusionary Illnesses for Systemic Exertion Intolerance Disease.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {5}, number = {2}, pages = {272-286}, pmid = {26854153}, issn = {2075-4418}, abstract = {The Institute of Medicine recently proposed a new case definition for chronic fatigue syndrome (CFS), as well as a new name, Systemic Exertion Intolerance Disease (SEID). Contrary to the Fukuda et al.'s CFS case definition, there are few exclusionary illnesses specified for this new SEID case definition. The current study explored this decision regarding exclusionary illnesses using the SEID criteria with four distinct data sets involving patients who had been identified as having CFS, as well as healthy controls, community controls, and other illness groups. The findings indicate that many individuals from major depressive disorder illness groups as well as other medical illnesses were categorized as having SEID. The past CFS Fukuda et al. prevalence rate in a community based sample of 0.42 increased by 2.8 times with the new SEID criteria. The consequences for this broadening of the case definition are discussed.}, } @article {pmid26853615, year = {2016}, author = {Kocazeybek, B and Yuksel, P}, title = {A contribution to the Torrey et al.'s "cat ownership inchildhood is a significant risk factor for later developing schizophrenia" study.}, journal = {Schizophrenia research}, volume = {172}, number = {1-3}, pages = {226}, doi = {10.1016/j.schres.2016.01.052}, pmid = {26853615}, issn = {1573-2509}, mesh = {Animals ; *Cats ; Humans ; *Pets ; Schizophrenia/*epidemiology ; }, } @article {pmid26851474, year = {2016}, author = {Dubé, PA and Imbeau, D and Dubeau, D and Lebel, L and Kolus, A}, title = {Removing the thermal component from heart rate provides an accurate VO2 estimation in forest work.}, journal = {Applied ergonomics}, volume = {54}, number = {}, pages = {148-157}, doi = {10.1016/j.apergo.2015.12.005}, pmid = {26851474}, issn = {1872-9126}, mesh = {Adult ; Aged ; Energy Metabolism/physiology ; Forestry/*methods ; Heart Rate/*physiology ; *Hot Temperature ; Humans ; Male ; Middle Aged ; *Oxygen Consumption ; Physical Exertion ; Quebec ; Work/*physiology ; Young Adult ; }, abstract = {Heart rate (HR) was monitored continuously in 41 forest workers performing brushcutting or tree planting work. 10-min seated rest periods were imposed during the workday to estimate the HR thermal component (ΔHRT) per Vogt et al. (1970, 1973). VO2 was measured using a portable gas analyzer during a morning submaximal step-test conducted at the work site, during a work bout over the course of the day (range: 9-74 min), and during an ensuing 10-min rest pause taken at the worksite. The VO2 estimated, from measured HR and from corrected HR (thermal component removed), were compared to VO2 measured during work and rest. Varied levels of HR thermal component (ΔHRTavg range: 0-38 bpm) originating from a wide range of ambient thermal conditions, thermal clothing insulation worn, and physical load exerted during work were observed. Using raw HR significantly overestimated measured work VO2 by 30% on average (range: 1%-64%). 74% of VO2 prediction error variance was explained by the HR thermal component. VO2 estimated from corrected HR, was not statistically different from measured VO2. Work VO2 can be estimated accurately in the presence of thermal stress using Vogt et al.'s method, which can be implemented easily by the practitioner with inexpensive instruments.}, } @article {pmid26836156, year = {2016}, author = {Robillard, JM}, title = {The Online Environment: A Key Variable in the Ethical Response to Complementary and Alternative Medicine for Alzheimer's Disease.}, journal = {Journal of Alzheimer's disease : JAD}, volume = {51}, number = {1}, pages = {11-13}, doi = {10.3233/JAD-150641}, pmid = {26836156}, issn = {1875-8908}, mesh = {*Alzheimer Disease ; *Complementary Therapies ; Humans ; }, abstract = {Racine et al.'s Ethics Review highlights the challenges associated with the use of complementary and alternative medicine (CAM) in the context of early diagnosis of Alzheimer's disease (AD). As CAM are increasingly promoted and sold on the Internet, the unregulated online environment has the potential to significantly impact the health and well-being of the aging demographic, and in particular of individuals concerned about AD. In this response, the ethical challenges specific to the online environment are discussed and solutions are put forward to empower the aging population to maximize the benefits of the online environment while minimizing the potential harms of misinformation, conflict of interest, and other ethical concerns.}, } @article {pmid26831873, year = {2016}, author = {Metz, JAJ and Geritz, SAH}, title = {Frequency dependence 3.0: an attempt at codifying the evolutionary ecology perspective.}, journal = {Journal of mathematical biology}, volume = {72}, number = {4}, pages = {1011-1037}, pmid = {26831873}, issn = {1432-1416}, mesh = {Animals ; Ecosystem ; Environment ; *Evolution, Molecular ; Genetic Fitness ; Genetics, Population ; Humans ; Mathematical Concepts ; *Models, Genetic ; Mutation ; Phenotype ; }, abstract = {The fitness concept and perforce the definition of frequency independent fitnesses from population genetics is closely tied to discrete time population models with non-overlapping generations. Evolutionary ecologists generally focus on trait evolution through repeated mutant substitutions in populations with complicated life histories. This goes with using the per capita invasion speed of mutants as their fitness. In this paper we develop a concept of frequency independence that attempts to capture the practical use of the term by ecologists, which although inspired by population genetics rarely fits its strict definition. We propose to call the invasion fitnesses of an eco-evolutionary model frequency independent when the phenotypes can be ranked by competitive strength, measured by who can invade whom. This is equivalent to the absence of weak priority effects, protected dimorphisms and rock-scissor-paper configurations. Our concept differs from that of Heino et al. (TREE 13:367-370, 1998) in that it is based only on the signs of the invasion fitnesses, whereas Heino et al. based their definitions on the structure of the feedback environment, summarising the effect of all direct and indirect interactions between individuals on fitness. As it turns out, according to our new definition an eco-evolutionary model has frequency independent fitnesses if and only if the effect of the feedback environment on the fitness signs can be summarised by a single scalar with monotonic effect. This may be compared with Heino et al.'s concept of trivial frequency dependence defined by the environmental feedback influencing fitness, and not just its sign, in a scalar manner, without any monotonicity restriction. As it turns out, absence of the latter restriction leaves room for rock-scissor-paper configurations. Since in 'realistic' (as opposed to toy) models frequency independence is exceedingly rare, we also define a concept of weak frequency dependence, which can be interpreted intuitively as almost frequency independence, and analyse in which sense and to what extent the restrictions on the potential model outcomes of the frequency independent case stay intact for models with weak frequency dependence.}, } @article {pmid26814625, year = {2016}, author = {Fuchsman, PC and Henning, MH and Magar, VS}, title = {Comment on "Exposure to mercury and Aroclor 1268 congeners in least terns (Sternula antillarum) in coastal Georgia, USA" by G. L. Robinson, G. L. Mills, A. H. Lindell, S. H. Schweitzer and S. M. Hernandez, Environmental Science: Processes & Impacts, 2015, 17, 1424.}, journal = {Environmental science. Processes & impacts}, volume = {18}, number = {2}, pages = {289-91; discussion 292-3}, doi = {10.1039/c5em00489f}, pmid = {26814625}, issn = {2050-7895}, mesh = {Animals ; Aroclors/*metabolism ; Charadriiformes/*metabolism ; *Environmental Monitoring ; Mercury/*metabolism ; Water Pollutants, Chemical/*metabolism ; }, abstract = {In a recent paper published in this journal (Robinson et al., Environmental Science: Processes & Impacts, 2015, 17, 1424), Robinson et al. reported concentrations of Aroclor 1268 congeners in least tern eggs in coastal Georgia, USA. This comment describes important omissions in Robinson et al.'s interpretation of those egg concentrations that alter the overall conclusions of the least tern study.}, } @article {pmid26806708, year = {2016}, author = {van Engen-Verheul, MM and Peute, LW and de Keizer, NF and Peek, N and Jaspers, MW}, title = {Optimizing the user interface of a data entry module for an electronic patient record for cardiac rehabilitation: A mixed method usability approach.}, journal = {International journal of medical informatics}, volume = {87}, number = {}, pages = {15-26}, doi = {10.1016/j.ijmedinf.2015.12.007}, pmid = {26806708}, issn = {1872-8243}, support = {MC_PC_13042/MRC_/Medical Research Council/United Kingdom ; MR/K006665/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Adult ; Animals ; *Attitude of Health Personnel ; *Cardiac Rehabilitation ; Cardiovascular Diseases/psychology/therapy ; Consumer Behavior/*statistics & numerical data ; Data Mining/*standards ; Decision Support Systems, Clinical/*standards ; Electronic Health Records/*statistics & numerical data ; Female ; Humans ; Male ; Meaningful Use ; Mice ; Middle Aged ; Physicians ; Practice Patterns, Physicians'/*standards ; Software ; User-Computer Interface ; Utilization Review ; }, abstract = {INTRODUCTION: Cumbersome electronic patient record (EPR) interfaces may complicate data-entry in clinical practice. Completeness of data entered in the EPR determines, among other things, the value of computerized clinical decision support (CCDS). Quantitative usability evaluations can provide insight into mismatches between the system design model of data entry and users' data entry behavior, but not into the underlying causes for these mismatches. Mixed method usability evaluation studies may provide these insights, and thus support generating redesign recommendations for improving an EPR system's data entry interface.

AIM: To improve the usability of the data entry interface of an EPR system with CCDS in the field of cardiac rehabilitation (CR), and additionally, to assess the value of a mixed method usability approach in this context.

METHODS: Seven CR professionals performed a think-aloud usability evaluation both before (beta-version) and after the redesign of the system. Observed usability problems from both evaluations were analyzed and categorized using Zhang et al.'s heuristic principles of good interface design. We combined the think-aloud usability evaluation of the system's beta-version with the measurement of a new usability construct: users' deviations in action sequence from the system's predefined data entry order sequence. Recommendations for redesign were implemented. We assessed whether the redesign improved CR professionals' (1) task efficacy (with respect to the completeness of data they collected), and (2) task efficiency (with respect to the average number of mouse clicks they needed to complete data entry subtasks).

RESULTS: With the system's beta version, 40% of health care professionals' navigation actions through the system deviated from the predefined next system action. The causes for these deviations as revealed by the think-aloud method mostly concerned mismatches between the system design model for data entry action sequences and users expectations of these action sequences, based on their paper-based daily routines. This caused non completion of data entry tasks (31% of main tasks completed), and more navigation actions than minimally required (146% of the minimum required). In the redesigned system the data entry navigational structure was organized in a flexible way around an overview screen to better mimic users' paper-based daily routines of collecting patient data. This redesign resulted in an increased number of completed main tasks (70%) and a decrease in navigation actions (133% of the minimum required). The think-aloud usability evaluation of the redesigned system showed that remaining problems concerned flexibility (e.g., lack of customization options) and consistency (mainly with layout and position of items on the screen).

CONCLUSION: The mixed method usability evaluation was supportive in revealing the magnitude and causes of mismatches between the system design model of data-entry with users' data entry behavior. However, as both task efficacy and efficiency were still not optimal with the redesigned EPR, we advise to perform a cognitive analysis on end users' mental processes and behavior patterns in daily work processes specifically during the requirements analysis phase of development of interactive healthcare information systems.}, } @article {pmid26786762, year = {2015}, author = {Eagly, AH}, title = {Mischaracterizing social psychology to support the laudable goal of increasing its political diversity.}, journal = {The Behavioral and brain sciences}, volume = {38}, number = {}, pages = {e141}, doi = {10.1017/S0140525X14001411}, pmid = {26786762}, issn = {1469-1825}, mesh = {Attitude ; *Goals ; Humans ; Politics ; Psychology ; *Psychology, Social ; }, abstract = {Duarte et al.'s arguments for increasing political diversity in social psychology are based on mischaracterizations of social psychology as fundamentally flawed in understanding stereotype accuracy and the effects of attitudes on information processing. I correct their misunderstandings while agreeing with their view that political diversity, along with other forms of diversity, stands to benefit social psychology.}, } @article {pmid26786631, year = {2015}, author = {Washington, N}, title = {Do we know how stressed we are?.}, journal = {The Behavioral and brain sciences}, volume = {38}, number = {}, pages = {e127}, doi = {10.1017/S0140525X14001757}, pmid = {26786631}, issn = {1469-1825}, mesh = {*Consciousness ; Humans ; *Unconscious, Psychology ; }, abstract = {I take issue with Kalisch et al.'s formulation of PASTOR, arguing that care must be taken in understanding what is meant by "appraisal." I examine the implications of PASTOR given two competing possibilities for what counts as an appraisal - first, if appraisal is restricted to conscious reflection on one's circumstances, and second, if appraisal is expanded to include subconscious mechanisms of evaluation.}, } @article {pmid26786133, year = {2015}, author = {Ross, L}, title = {What kinds of conservatives does social psychology lack, and why?.}, journal = {The Behavioral and brain sciences}, volume = {38}, number = {}, pages = {e156}, doi = {10.1017/S0140525X14001368}, pmid = {26786133}, issn = {1469-1825}, mesh = {Dissent and Disputes ; Humans ; *Politics ; *Psychology, Social ; }, abstract = {Although Duarte et al.'s claims about the potential benefits of greater political diversity in the ranks of social psychology are apt, their discussion of the decline in such diversity, the role played by self-selection, and the specific domains they cite in discussing an anti-conservative bias raise issues that merit closer examination. The claim that sound research and analysis challenging liberal orthodoxies fails to receive a fair hearing in our journals and professional discourse is also disputed.}, } @article {pmid26785906, year = {2015}, author = {Soenke, M and O'Connor, MF and Greenberg, J}, title = {Broadening the definition of resilience and "reappraising" the use of appetitive motivation.}, journal = {The Behavioral and brain sciences}, volume = {38}, number = {}, pages = {e121}, doi = {10.1017/S0140525X14001691}, pmid = {26785906}, issn = {1469-1825}, mesh = {Humans ; *Motivation ; }, abstract = {Kalisch et al.'s PASTOR model synthesizes current knowledge of resilience, focusing on mechanisms as a common pathway to outcomes and highlighting neuroscience as a method for exploring this. We propose the model broaden its definition of resiliency to include positive indices of recovery, include positive affect as a mechanism, and approach motivation as distinct from overcoming aversive motivation.}, } @article {pmid26785389, year = {2016}, author = {Ballestri, S and Nascimbeni, F and Romagnoli, D and Lonardo, A}, title = {The independent predictors of non-alcoholic steatohepatitis and its individual histological features.: Insulin resistance, serum uric acid, metabolic syndrome, alanine aminotransferase and serum total cholesterol are a clue to pathogenesis and candidate targets for treatment.}, journal = {Hepatology research : the official journal of the Japan Society of Hepatology}, volume = {46}, number = {11}, pages = {1074-1087}, doi = {10.1111/hepr.12656}, pmid = {26785389}, issn = {1386-6346}, abstract = {AIM: The diagnosis of non-alcoholic steatohepatitis (NASH) is based on the individual histological features: steatosis, lobular inflammation and ballooning. Non-alcoholic fatty liver disease (NAFLD) activity score (NAS ≥ 5) is used in clinical trials. Fibrosis dictates long-term NAFLD prognosis. Recently, more-than-mild portal inflammation has raised interest as a marker of NAFLD severity. We assessed the independent predictors of: (I) individual histological lesions of NASH; (II) diagnosis of NASH; (III) significant (stage ≥2) and advanced (stage ≥3) fibrosis; and (IV) more-than-mild portal inflammation.

METHODS: Data from 118 consecutive biopsy-proven NAFLD patients observed at our institution were retrospectively analyzed.

RESULTS: At stepwise multivariate logistic regression analyses, independent predictors were as follows. For the individual histological features of NASH: insulin resistance (IR), assessed with Homeostasis Model Assessment-IR (HOMA-IR), serum uric acid (SUA) and serum total cholesterol (TCH) for moderate-to-severe steatosis; waist circumference (waist), HOMA-IR and TCH for lobular inflammation; waist, HOMA-IR, metabolic syndrome (MS), serum alanine aminotransferase (ALT), SUA and TCH for ballooning. For NASH diagnosis: waist, HOMA-IR, MS, ALT, SUA and TCH (Brunt et al.'s classification); ALT, SUA and TCH for NAS ≥ 5. For significant and advanced fibrosis, respectively: waist, MS and ALT; age, platelets, HOMA-IR, diabetes and TCH. For more-than-mild portal inflammation: serum aspartate aminotransferase (AST), serum iron, NAS ≥ 5 and significant liver fibrosis.

CONCLUSION: HOMA-IR, SUA, MS, ALT and TCH are independent predictors of NASH and its individual histological lesions, notably including fibrosis. Based on our findings, these factors should be considered major pathogenic drivers of NASH and, by inference, potential targets for treatment.}, } @article {pmid26784917, year = {2016}, author = {Gallant, SN}, title = {Mindfulness meditation practice and executive functioning: Breaking down the benefit.}, journal = {Consciousness and cognition}, volume = {40}, number = {}, pages = {116-130}, doi = {10.1016/j.concog.2016.01.005}, pmid = {26784917}, issn = {1090-2376}, mesh = {Executive Function/*physiology ; Humans ; *Inhibition, Psychological ; *Meditation ; *Mindfulness ; }, abstract = {This paper focuses on evidence for mindfulness meditation-related benefits to executive functioning, processes important for much of human volitional behaviour. Miyake et al. (2000) have shown that executive functions can be fractionated into three distinct domains including inhibition, working memory updating, and mental set shifting. Considering these separable domains, it is important to determine whether the effects of mindfulness can generalize to all three sub-functions or are specific to certain domains. To address this, the current review applied Miyake et al.'s (2000) fractionated model of executive functioning to the mindfulness literature. Empirical studies assessing the benefits of mindfulness to measures tapping the inhibition, updating, and shifting components of executive functioning were examined. Results suggest a relatively specific as opposed to general benefit resulting from mindfulness, with consistent inhibitory improvement, but more variable advantages to the updating and shifting domains. Recommendations surrounding application of mindfulness practice and future research are discussed.}, } @article {pmid26767195, year = {2016}, author = {Qin, F and Ding, L and Zhang, L and Monticone, F and Chum, CC and Deng, J and Mei, S and Li, Y and Teng, J and Hong, M and Zhang, S and Alù, A and Qiu, CW}, title = {Hybrid bilayer plasmonic metasurface efficiently manipulates visible light.}, journal = {Science advances}, volume = {2}, number = {1}, pages = {e1501168}, pmid = {26767195}, issn = {2375-2548}, mesh = {Equipment Design/methods ; Light ; Nanotechnology/*methods ; Surface Plasmon Resonance/*methods ; }, abstract = {Metasurfaces operating in the cross-polarization scheme have shown an interesting degree of control over the wavefront of transmitted light. Nevertheless, their inherently low efficiency in visible light raises certain concerns for practical applications. Without sacrificing the ultrathin flat design, we propose a bilayer plasmonic metasurface operating at visible frequencies, obtained by coupling a nanoantenna-based metasurface with its complementary Babinet-inverted copy. By breaking the radiation symmetry because of the finite, yet small, thickness of the proposed structure and benefitting from properly tailored intra- and interlayer couplings, such coupled bilayer metasurface experimentally yields a conversion efficiency of 17%, significantly larger than that of earlier single-layer designs, as well as an extinction ratio larger than 0 dB, meaning that anomalous refraction dominates the transmission response. Our finding shows that metallic metasurface can counterintuitively manipulate the visible light as efficiently as dielectric metasurface (~20% in conversion efficiency in Lin et al.'s study), although the metal's ohmic loss is much higher than dielectrics. Our hybrid bilayer design, still being ultrathin (~λ/6), is found to obey generalized Snell's law even in the presence of strong couplings. It is capable of efficiently manipulating visible light over a broad bandwidth and can be realized with a facile one-step nanofabrication process.}, } @article {pmid26766384, year = {2017}, author = {Zhang, L and Zhu, S and Tang, S}, title = {Privacy Protection for Telecare Medicine Information Systems Using a Chaotic Map-Based Three-Factor Authenticated Key Agreement Scheme.}, journal = {IEEE journal of biomedical and health informatics}, volume = {21}, number = {2}, pages = {465-475}, doi = {10.1109/JBHI.2016.2517146}, pmid = {26766384}, issn = {2168-2208}, mesh = {Algorithms ; Computer Security ; *Confidentiality ; *Electronic Health Records ; Humans ; Privacy ; *Telemedicine ; }, abstract = {Telecare medicine information systems (TMIS) provide flexible and convenient e-health care. However, the medical records transmitted in TMIS are exposed to unsecured public networks, so TMIS are more vulnerable to various types of security threats and attacks. To provide privacy protection for TMIS, a secure and efficient authenticated key agreement scheme is urgently needed to protect the sensitive medical data. Recently, Mishra et al. proposed a biometrics-based authenticated key agreement scheme for TMIS by using hash function and nonce, they claimed that their scheme could eliminate the security weaknesses of Yan et al.'s scheme and provide dynamic identity protection and user anonymity. In this paper, however, we demonstrate that Mishra et al.'s scheme suffers from replay attacks, man-in-the-middle attacks and fails to provide perfect forward secrecy. To overcome the weaknesses of Mishra et al.'s scheme, we then propose a three-factor authenticated key agreement scheme to enable the patient to enjoy the remote healthcare services via TMIS with privacy protection. The chaotic map-based cryptography is employed in the proposed scheme to achieve a delicate balance of security and performance. Security analysis demonstrates that the proposed scheme resists various attacks and provides several attractive security properties. Performance evaluation shows that the proposed scheme increases efficiency in comparison with other related schemes.}, } @article {pmid26756174, year = {2016}, author = {Li, Z and Durgin, FH}, title = {Perceived azimuth direction is exaggerated: Converging evidence from explicit and implicit measures.}, journal = {Journal of vision}, volume = {16}, number = {1}, pages = {4}, pmid = {26756174}, issn = {1534-7362}, support = {R15 EY021026/EY/NEI NIH HHS/United States ; }, mesh = {Adult ; Anisotropy ; Cues ; Distance Perception/*physiology ; Female ; Humans ; Male ; Models, Theoretical ; Orientation ; Visual Perception/*physiology ; }, abstract = {Recent observations suggest that perceived visual direction in the sagittal plane (angular direction in elevation, both upward and downward from eye level) is exaggerated. Foley, Ribeiro-Filho, and Da Silva's (2004) study of perceived size of exocentric ground extent implies that perceived angular direction in azimuth may also be exaggerated. In the present study, we directly examined whether perceived azimuth direction is overestimated. In Experiment 1, numeric estimates of azimuth direction (-48° to 48° relative to straight ahead) were obtained. The results showed a linear exaggeration in perceived azimuth direction with a gain of about 1.26. In Experiment 2, a perceptual extent-matching task served as an implicit measure of perceived azimuth direction. Participants matched an egocentric distance in one direction to a frontal extent in nearly the opposite direction. The angular biases implied by the matching data well replicated Foley et al.'s finding and were also fairly consistent with the azimuth bias function found in Experiment 1, although a slight overall shift was observed between the results of the two experiments. Experiment 3, in which half the observers were tilted sideways while making frontal/depth extent comparisons, suggested that the discrepancy between the results of Experiment 1 and 2 can partially be explained by a retinal horizontal vertical illusion affecting distance estimation tasks. Overall the present study provides converging evidence to suggest that the perception of azimuth direction is overestimated.}, } @article {pmid26752608, year = {2016}, author = {Camperio Ciani, AS and Battaglia, U and Liotta, M}, title = {Response: Avuncularity and Kin Selection in Homosexuals: A Problematic Test or a Problematic Hypothesis?.}, journal = {Journal of sex research}, volume = {53}, number = {2}, pages = {153-156}, doi = {10.1080/00224499.2015.1115809}, pmid = {26752608}, issn = {1559-8519}, mesh = {*Homosexuality, Male ; Humans ; Male ; *Sexual Behavior ; }, abstract = {Here we respond to Vasey et al.'s critical comments regarding our article, "Societal norms rather than sexual orientation influence kin altruism and avuncularity in tribal Urak-Lawoi, Italian, and Spanish adult males" (Camperio Ciani, Battaglia, & Liotta, 2015 , JSR doi:10.1080/00224499.2014.993748). The first regards the selection of the Urak-Lawoi population of Ko Lipeh, which is considered too modern and touristic to be adequate to test the kin selection and avuncular hypothesis for homosexuality. We provide historical evidence of the contrary, and show that the population at the inception of our 10 years research was indeed primitive and tribal, and probands actually grew and lived in such a society. Only a few years after the 2004 tsunami, the island was developed and invaded by mass tourism. The second comment regarded the statistical analysis and interpretation of data. We show that we consistently and conservatively considered the effects of all confounding variables, both with comparative tests, and by a series of multivariate regression analyses. This was the orthodox procedure approved by all other reviewers. In conclusion, even addressing these comments, we maintain that the kin selection and avuncularity hypothesis for homosexuality is not supported by empirical data even in this primitive and tribal society.}, } @article {pmid26743628, year = {2016}, author = {Moon, J and Choi, Y and Kim, J and Won, D}, title = {An Improvement of Robust and Efficient Biometrics Based Password Authentication Scheme for Telecare Medicine Information Systems Using Extended Chaotic Maps.}, journal = {Journal of medical systems}, volume = {40}, number = {3}, pages = {70}, pmid = {26743628}, issn = {1573-689X}, mesh = {Biometric Identification/*methods ; *Computer Security ; Confidentiality ; Health Smart Cards/*methods ; Humans ; Information Systems/*standards ; Nonlinear Dynamics ; Telemedicine/*standards ; }, abstract = {Recently, numerous extended chaotic map-based password authentication schemes that employ smart card technology were proposed for Telecare Medical Information Systems (TMISs). In 2015, Lu et al. used Li et al.'s scheme as a basis to propose a password authentication scheme for TMISs that is based on biometrics and smart card technology and employs extended chaotic maps. Lu et al. demonstrated that Li et al.'s scheme comprises some weaknesses such as those regarding a violation of the session-key security, a vulnerability to the user impersonation attack, and a lack of local verification. In this paper, however, we show that Lu et al.'s scheme is still insecure with respect to issues such as a violation of the session-key security, and that it is vulnerable to both the outsider attack and the impersonation attack. To overcome these drawbacks, we retain the useful properties of Lu et al.'s scheme to propose a new password authentication scheme that is based on smart card technology and requires the use of chaotic maps. Then, we show that our proposed scheme is more secure and efficient and supports security properties.}, } @article {pmid26742086, year = {2016}, author = {Carroll, B and Maetzel, D and Maddocks, OD and Otten, G and Ratcliff, M and Smith, GR and Dunlop, EA and Passos, JF and Davies, OR and Jaenisch, R and Tee, AR and Sarkar, S and Korolchuk, VI}, title = {Control of TSC2-Rheb signaling axis by arginine regulates mTORC1 activity.}, journal = {eLife}, volume = {5}, number = {}, pages = {}, pmid = {26742086}, issn = {2050-084X}, support = {104158/WT_/Wellcome Trust/United Kingdom ; 19702/CRUK_/Cancer Research UK/United Kingdom ; BB/H022384/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; MR/K006312/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Arginine/*metabolism ; Cell Differentiation ; Embryonic Stem Cells/physiology ; Humans ; Mechanistic Target of Rapamycin Complex 1 ; Monomeric GTP-Binding Proteins/*metabolism ; Multiprotein Complexes/*metabolism ; Neuropeptides/*metabolism ; Ras Homolog Enriched in Brain Protein ; *Signal Transduction ; TOR Serine-Threonine Kinases/*metabolism ; Tuberous Sclerosis Complex 2 Protein ; Tumor Suppressor Proteins/*metabolism ; }, abstract = {The mammalian target of rapamycin complex 1 (mTORC1) is the key signaling hub that regulates cellular protein homeostasis, growth, and proliferation in health and disease. As a prerequisite for activation of mTORC1 by hormones and mitogens, there first has to be an available pool of intracellular amino acids. Arginine, an amino acid essential during mammalian embryogenesis and early development is one of the key activators of mTORC1. Herein, we demonstrate that arginine acts independently of its metabolism to allow maximal activation of mTORC1 by growth factors via a mechanism that does not involve regulation of mTORC1 localization to lysosomes. Instead, arginine specifically suppresses lysosomal localization of the TSC complex and interaction with its target small GTPase protein, Rheb. By interfering with TSC-Rheb complex, arginine relieves allosteric inhibition of Rheb by TSC. Arginine cooperates with growth factor signaling which further promotes dissociation of TSC2 from lysosomes and activation of mTORC1. Arginine is the main amino acid sensed by the mTORC1 pathway in several cell types including human embryonic stem cells (hESCs). Dependence on arginine is maintained once hESCs are differentiated to fibroblasts, neurons, and hepatocytes, highlighting the fundamental importance of arginine-sensing to mTORC1 signaling. Together, our data provide evidence that different growth promoting cues cooperate to a greater extent than previously recognized to achieve tight spatial and temporal regulation of mTORC1 signaling.}, } @article {pmid26726034, year = {2015}, author = {Seshia, SS}, title = {A 'reluctant' critical review: 'Manual for evidence-based clinical practice (2015)'.}, journal = {Journal of evaluation in clinical practice}, volume = {21}, number = {6}, pages = {995-1005}, doi = {10.1111/jep.12509}, pmid = {26726034}, issn = {1365-2753}, mesh = {Clinical Decision-Making ; Diagnostic Techniques and Procedures/standards ; Evidence-Based Medicine/*standards ; Humans ; Manuals as Topic/*standards ; Randomized Controlled Trials as Topic/standards ; }, abstract = {BACKGROUND: The Users' Guides to the Medical Literature Manual has been a major influence on the teaching and practice of health care globally.

METHODS: The 3rd edition of the multi-authored Manual was reviewed using the principles outlined in Evidence-based Medicine (EBM) texts. One 'clinical scenario' was selected for critical appraisal, as were several chapters; objectivity was enhanced by citing references to support opinions. RESULTS (SUMMARY OF THE APPRAISAL): (1) Strengths: Clinical pearls, too numerous to list.

EXAMPLES: (i) evidence is never enough to drive clinical decision making; (ii) do not rush to adopt new interventions; and (iii) question efficacy data based only on surrogate markers. (2) Weaknesses: The Manual shares shortcomings of textbooks discussed by Straus et al.: (i) references may not be current, important ones may be excluded and citations may be selective; (ii) often, opinion-based; and (iii) delays between revisions. (3) Notable omissions: Little or no discussion of: (i) important segments of the population: those <18 years of age, >65 years of age and those with multimorbidity; (ii) surgical disciplines; (iii) Greenhalgh et al.'s essay on EBM; (iv) alternate views on the hierarchy of evidence; and (vi) critical thinking. (4) Additional issues: (i) Omission of important references on dabigatran (clinical scenario: chapter 13.1); (ii) authors' advice (Chapter 13.3) to 'bypass the discussion section of published research'; and (iii) the advocacy of pre-appraised sources of evidence and network meta-analysis without warnings about limitations, are critiqued.

CONCLUSION: The Manual has several clinical pearls but readers should also be aware of shortcomings.}, } @article {pmid26725150, year = {2016}, author = {Dickson, H and Kavanagh, DJ and MacLeod, C}, title = {The pulling power of chocolate: Effects of approach-avoidance training on approach bias and consumption.}, journal = {Appetite}, volume = {99}, number = {}, pages = {46-51}, doi = {10.1016/j.appet.2015.12.026}, pmid = {26725150}, issn = {1095-8304}, mesh = {*Avoidance Learning ; *Chocolate ; Choice Behavior ; Energy Intake ; Feeding Behavior/*psychology ; Female ; Food Preferences/*psychology ; Humans ; Male ; Photic Stimulation ; Random Allocation ; Surveys and Questionnaires ; Taste ; Young Adult ; }, abstract = {Previous research has shown that action tendencies to approach alcohol may be modified using computerized Approach-Avoidance Task (AAT), and that this impacted on subsequent consumption. A recent paper in this journal (Becker, Jostman, Wiers, & Holland, 2015) failed to show significant training effects for food in three studies: Nor did it find effects on subsequent consumption. However, avoidance training to high calorie foods was tested against a control rather than Approach training. The present study used a more comparable paradigm to the alcohol studies. It randomly assigned 90 participants to 'approach' or 'avoid' chocolate images on the AAT, and then asked them to taste and rate chocolates. A significant interaction of condition and time showed that training to avoid chocolate resulted in faster avoidance responses to chocolate images, compared with training to approach it. Consistent with Becker et al.'s Study 3, no effect was found on amounts of chocolate consumed, although a newly published study in this journal (Schumacher, Kemps, & Tiggemann, 2016) did do so. The collective evidence does not as yet provide solid basis for the application of AAT training to reduction of problematic food consumption, although clinical trials have yet to be conducted.}, } @article {pmid26721291, year = {2016}, author = {Schmidlin, EA and Jones, KS}, title = {Do Tele-Operators Learn to Better Judge Whether a Robot Can Pass Through an Aperture?.}, journal = {Human factors}, volume = {58}, number = {2}, pages = {360-369}, doi = {10.1177/0018720815617849}, pmid = {26721291}, issn = {1547-8181}, mesh = {Adolescent ; Adult ; Female ; Humans ; *Learning ; Male ; *Man-Machine Systems ; Observer Variation ; Research Design/*standards ; *Task Performance and Analysis ; *Telecommunications ; Young Adult ; }, abstract = {OBJECTIVE: This experiment examined whether tele-operators learn to better judge a robot's ability to pass through an aperture, hereafter referred to as pass-ability judgments, and detailed the nature of such learning.

BACKGROUND: Jones, Johnson, and Schmidlin reported that tele-operators' pass-ability judgments did not improve over the course of their experiment, which was surprising.

METHOD: In each of seven blocks, tele-operators made pass-ability judgments about 10 apertures whose width varied. During each trial, participants drove the robot toward the aperture, answered yes or no to whether it could pass through that aperture, and then attempted to drive the robot through the aperture. Pass-ability judgments were analyzed in terms of percentage correct and absolute thresholds; the latter mimicked how Jones et al. analyzed their data.

RESULTS: Learning was revealed when judgments were analyzed in terms of percentage correct and not when analyzed in terms of absolute thresholds. Further analyses revealed that tele-operators only improved their pass-ability judgments for impassable apertures, and tele-operators' perceptual sensitivity and response bias changed over the course of the experiment.

CONCLUSION: The percentage correct-based analyses revealed that tele-operators learned to make better pass-ability judgments. Jones et al.'s decision to analyze their data in terms of absolute thresholds obscured learning.

APPLICATION: The present results suggested that researchers should employ percentage correct when studying learning in this domain, training protocols should focus on improving tele-operators' abilities to judge the pass-ability of impassable apertures, and tele-operators truly learned to better discriminate passable and impassable apertures.}, } @article {pmid29105407, year = {2016}, author = {Berraondo Fraile, J and Juan Samper, G and Fernández-Fabrellas, E and Konishi, I and López Vazquéz, A and Bediaga Collado, A and Ramón Capilla, M}, title = {[D-dimer testing in the emergency department: age adjustment, inappropriate use, and ability to predict the extension and severity of pulmonary embolism].}, journal = {Emergencias : revista de la Sociedad Espanola de Medicina de Emergencias}, volume = {28}, number = {4}, pages = {223-228}, pmid = {29105407}, issn = {2386-5857}, abstract = {OBJECTIVES: To evaluate whether using D-dimer test results adjusted for age according to the formula proposed by Douma et al. improves diagnostic accuracy; to assess the appropriateness of ordering D-dimer tests on clinical suspicion of pulmonary embolism; and to explore the association of test results with the extension and severity of the embolism.

MATERIAL AND METHODS: Retrospective observational study of 1833 cases in which D-dimer testing was ordered for patients in our hospital's emergency department in the course of a year. We calculated sensitivity, specificity, and positive and negative predictive values using our hospital's D-dimer cutoff of 250 μg/mL adjusted for age with a modification of Douma et al.'s formula. When information about pulmonary embolism extension and severity was on record, we assessed the correlation with test results.

RESULTS: Adjusting D-dimer level for age increased the number of true negatives and the specificity and positive predictive value of the test. D-dimer level correlated significantly with the extension of pulmonary embolism (r=0.41, P<.05) but not with clinical severity.

CONCLUSION: Adjusting the D-dimer test result by age improves accuracy in the diagnosis of pulmonary embolism, even though clinical suspicion in Spain does not follow guideline recommendations. Our findings suggest that Ddimer level correlates with the extension but not the severity of pulmonary embolism.}, } @article {pmid28768396, year = {2016}, author = {Strauss, MB}, title = {Concerns regarding Fedorko, et al.'s article: Hyperbaric oxygen does not reduce indications.}, journal = {Undersea & hyperbaric medicine : journal of the Undersea and Hyperbaric Medical Society, Inc}, volume = {43}, number = {6}, pages = {742-743}, pmid = {28768396}, issn = {1066-2936}, mesh = {Amputation, Surgical ; *Diabetes Mellitus ; Double-Blind Method ; Humans ; *Hyperbaric Oxygenation ; Lower Extremity ; Prospective Studies ; Ulcer ; }, } @article {pmid28355833, year = {2016}, author = {Prinz, W}, title = {Explaining consciousness: From correlations to foundations.}, journal = {The Behavioral and brain sciences}, volume = {39}, number = {}, pages = {e193}, doi = {10.1017/S0140525X1500223X}, pmid = {28355833}, issn = {1469-1825}, mesh = {*Consciousness ; Humans ; Knowledge ; }, abstract = {What does it take to explain the roles of consciousness for action and action for consciousness? This commentary claims that efficient functional explanations must meet two epistemological requirements: independent description of explanandum and explanans, and foundational explanation of their mutual relationship. It is argued that Morsella et al.'s target articledoes not fully meet these requirements.}, } @article {pmid28355830, year = {2016}, author = {Keller, A}, title = {Is conscious content available only to the skeletal muscle system?.}, journal = {The Behavioral and brain sciences}, volume = {39}, number = {}, pages = {e183}, doi = {10.1017/S0140525X15002137}, pmid = {28355830}, issn = {1469-1825}, mesh = {Brain ; *Consciousness ; Humans ; Muscle, Skeletal/*physiology ; }, abstract = {I applaud Morsella et al.'s approach to investigate consciousness in terms of behavioral control. After all, the function of the brain is to control behavior, and consciousness contributes to the function of the brain. However, I question whether conscious content is available only to the skeletal muscle system, as the principle of parallel responses into skeletal muscle (PRISM) (Morsella 2005) proposes.}, } @article {pmid28355829, year = {2016}, author = {de Vries, J and Ward, LM}, title = {An "ecological" action-based synthesis.}, journal = {The Behavioral and brain sciences}, volume = {39}, number = {}, pages = {e173}, doi = {10.1017/S0140525X15002046}, pmid = {28355829}, issn = {1469-1825}, mesh = {Biological Evolution ; *Ecology ; Humans ; Models, Theoretical ; *Perception ; }, abstract = {We expand upon Morsella et al.'s synthesis in the direction of what Gibson (1979) called an ecological approach to perception. Morsella et al. describe consciousness as a director of voluntary action, but they understate the role of the environment in its evolution as well as in directing behavior. We elaborate these roles in the context of the concept of affordances.}, } @article {pmid28355812, year = {2016}, author = {D'Souza, H and Bremner, AJ}, title = {Calling for a developmental perspective on action-based consciousness.}, journal = {The Behavioral and brain sciences}, volume = {39}, number = {}, pages = {e174}, doi = {10.1017/S0140525X15002034}, pmid = {28355812}, issn = {1469-1825}, mesh = {*Child Development ; *Consciousness ; Humans ; Infant, Newborn ; }, abstract = {Human newborns can resolve some response conflicts in order to adapt their behaviour, suggesting that the newborn has consciousness according to Morsella et al.'s framework. However, we pose a range of developmental questions regarding Morsella et al.'s account, especially concerning the role of consciousness in the development of action.}, } @article {pmid28355794, year = {2016}, author = {Kruger, E and Vigil, JM and Stith, SS}, title = {Task specificity and the impact on both the individual and group during the formation of groups.}, journal = {The Behavioral and brain sciences}, volume = {39}, number = {}, pages = {e156}, doi = {10.1017/S0140525X15001442}, pmid = {28355794}, issn = {1469-1825}, mesh = {*Group Processes ; Humans ; *Individuality ; }, abstract = {We agree with aspects of Baumeister et al.'s view that shared identities are necessary during initial stages of group formation. In contrast to their analysis, however, we provide evidence that the value of self-differentiation depends more on the task itself than on the stage of group development and challenge the authors to focus on the functions of the group.}, } @article {pmid28355782, year = {2016}, author = {de Baca, TC and Garcia, RA and Woodley, MA and Figueredo, AJ}, title = {Considering the role of ecology on individual differentiation.}, journal = {The Behavioral and brain sciences}, volume = {39}, number = {}, pages = {e145}, pmid = {28355782}, issn = {1469-1825}, support = {T32 MH019391/MH/NIMH NIH HHS/United States ; }, mesh = {Ecology ; Humans ; *Social Behavior ; }, abstract = {Our commentary articulates some of the commonalities between Baumeister et al.'s theory of socially differentiated roles and Strategic Differentiation-Integration Effort. We expand upon the target article's position by arguing that differentiating social roles is contextual and driven by varying ecological pressures, producing character displacement not only among individuals within complex societies, but also across social systems and multiple levels of organization.}, } @article {pmid28332974, year = {2016}, author = {Ehlers, S and Rucks, J and Severin, D}, title = {Contraceptives Can Unite Us.}, journal = {World health & population}, volume = {17}, number = {1}, pages = {26-30}, doi = {10.12927/whp.2016.25039}, pmid = {28332974}, issn = {1718-3340}, abstract = {Dyer et al.'s (2016) analysis offers key insights into religious conservatives' perceptions of family planning. It also provides the basis for a messaging platform which could help grow support for sexual and reproductive health programming in a highly politicized environment. However, Dyer et al. have put forth a potentially harmful premise in their exclusive focus on "healthy timing and spacing of pregnancies" (HTSP), while ignoring the benefits of making "contraceptives" central to messaging efforts to increase the support of religious conservatives. Not only does the term "contraceptives" elicit the most positive results among those tested, it appeals to reproductive health advocates by avoiding the pitfalls of a singular focus on HTSP, including ignoring the sexual and reproductive needs and rights of those who are unmarried, adolescents and youth, survivors of gender-based violence - and those who simply wish to limit births entirely.}, } @article {pmid28332968, year = {2016}, author = {Sinha, SK}, title = {Without Empowered Patients, Caregivers and Providers, a Community-Based Dementia Care Strategy Will Remain Just That.}, journal = {HealthcarePapers}, volume = {16}, number = {2}, pages = {64-70}, doi = {10.12927/hcpap.2017.25000}, pmid = {28332968}, issn = {1488-917X}, mesh = {*Caregivers ; *Dementia ; Humans ; Ontario ; }, abstract = {In trying to cope with the needs of the growing number of people living with dementia (PLWD), jurisdictions around the world have been implementing a variety of strategies, policies and programs to enable better access to the supports they and those who care for them require. Despite considerable efforts that have been undertaken, PLWD and their caregivers still face considerable challenges in pursuing care pathways and community-based supports that can help them avoid premature institutionalization. Morton-Chang et al. (2016) have comprehensively reviewed jurisdictional approaches towards the development of dementia strategies, policies and programs; there is a growing understanding and consensus around the things we need to do as societies to better meet the needs of PLWD and their caregivers; however, progress to date could be best characterized as top-down, patchy and fragmented. This paper builds on Morton-Chang et al.'s (2016) assertion that the development of a comprehensive person and caregiver-centred community-based dementia strategy in Ontario and other parts of Canada is likely achievable, particularly if implemented using a "ground-up" approach that is well-aligned with other government-related initiatives.}, } @article {pmid26720595, year = {2016}, author = {Jiang, X and Reiter, G and Hu, W}, title = {How Chain-Folding Crystal Growth Determines the Thermodynamic Stability of Polymer Crystals.}, journal = {The journal of physical chemistry. B}, volume = {120}, number = {3}, pages = {566-571}, doi = {10.1021/acs.jpcb.5b09324}, pmid = {26720595}, issn = {1520-5207}, abstract = {Chain-folding is a habit of polymer crystallization, which yields limited lamellar thickness of polymer crystals and thus determines their thermodynamic stability. We performed dynamic Monte Carlo simulations of a lattice polymer model with chain-folded lamellar crystal growth stopped by a critical spacing of two parallel-oriented bars. We confirmed the critical spacing as minimum lamellar thickness (lmin) proposed previously in the Lauritzen-Hoffman (LH) model; however, the temperature dependence of excess lamellar thickness beyond lmin appears opposite to the prediction of the LH model. Moreover, it reproduces Strobl et al.'s experimental observations, but our lattice-model approach rules out any mesophase hypothesis. We proposed a kinetic model combining intramolecular secondary nucleation and stem elongation to explain this temperature-dependence behavior, which reconciles the controversial arguments on the microscopic mechanism of lamellar crystal growth of polymers.}, } @article {pmid26713011, year = {2015}, author = {Cyril, AC and Nair, SS and Mathai, A and Kannoth, S and Thomas, SV}, title = {Autoimmune encephalitis: Clinical diagnosis versus antibody confirmation.}, journal = {Annals of Indian Academy of Neurology}, volume = {18}, number = {4}, pages = {408-411}, pmid = {26713011}, issn = {0972-2327}, abstract = {CONTEXT: Autoimmune encephalitis is a heterogeneous disorder which is being diagnosed with increasing frequency. The diagnosis of these disorders is based on the detection of autoantibodies and characteristic clinical profiles.

AIMS: We aimed to study the antibody profile in encephalitis patients with suspected autoimmune etiology presenting to a tertiary care center.

SETTINGS AND DESIGN: The subjects were selected by screening all patients with clinical profile suggesting autoimmune encephalitis admitted in the neuromedical intensive care unit (ICU) of a tertiary care center in South India.

MATERIALS AND METHODS: Patients who fulfilled modified Zuliani et al.'s, criteria for autoimmune encephalitis were identified during the period December 2009-June 2013. Blood samples from these subjects were screened for six neuronal antibodies.

STATISTICAL ANALYSIS USED: Chi-square test was applied to compare the antibody positive and negative patients.

RESULTS: Out of 1,227 patients screened, 39 subjects (14 males: 25 females) were identified with a mean age of 15.95 years and 19 cases were assessed in the acute and 20 in the convalescent phase of the illness. Seizure (87.8 %) was the most common presenting symptom; status epilepticus occurred in 23 (60.5%) patients during the course of the illness. Fourteen (35.9%) patients were N-methyl-D-aspartate receptor (NMDAR) antibody-positive and all were negative for the other antibodies tested.

CONCLUSIONS: One-third of patients presenting with acute noninfective encephalitis would be positive for NMDAR antibodies with the remaining two-thirds with clinically suspected autoimmune encephalitis being antibody-negative. There are few markers in the clinical and investigative profiles to distinguish antibody-positive and -negative patients.}, } @article {pmid26709702, year = {2015}, author = {Moon, J and Choi, Y and Jung, J and Won, D}, title = {An Improvement of Robust Biometrics-Based Authentication and Key Agreement Scheme for Multi-Server Environments Using Smart Cards.}, journal = {PloS one}, volume = {10}, number = {12}, pages = {e0145263}, pmid = {26709702}, issn = {1932-6203}, mesh = {Biometric Identification/*methods ; *Computer Security ; Computers ; Confidentiality ; Health Smart Cards/*methods ; Humans ; *User-Computer Interface ; }, abstract = {In multi-server environments, user authentication is a very important issue because it provides the authorization that enables users to access their data and services; furthermore, remote user authentication schemes for multi-server environments have solved the problem that has arisen from user's management of different identities and passwords. For this reason, numerous user authentication schemes that are designed for multi-server environments have been proposed over recent years. In 2015, Lu et al. improved upon Mishra et al.'s scheme, claiming that their remote user authentication scheme is more secure and practical; however, we found that Lu et al.'s scheme is still insecure and incorrect. In this paper, we demonstrate that Lu et al.'s scheme is vulnerable to outsider attack and user impersonation attack, and we propose a new biometrics-based scheme for authentication and key agreement that can be used in multi-server environments; then, we show that our proposed scheme is more secure and supports the required security properties.}, } @article {pmid26709635, year = {2017}, author = {Martinsson, S and Rhodén, C and Erséus, C}, title = {Barcoding gap, but no support for cryptic speciation in the earthworm Aporrectodea longa (Clitellata: Lumbricidae).}, journal = {Mitochondrial DNA. Part A, DNA mapping, sequencing, and analysis}, volume = {28}, number = {2}, pages = {147-155}, doi = {10.3109/19401736.2015.1115487}, pmid = {26709635}, issn = {2470-1408}, mesh = {Animals ; Cell Nucleus ; *DNA Barcoding, Taxonomic ; *DNA, Mitochondrial ; Electron Transport Complex IV/genetics ; Genes, Mitochondrial ; Genetic Variation ; Histones/genetics ; Oligochaeta/*classification/genetics/metabolism ; *Phylogeny ; }, abstract = {DNA-barcoding, using the mitochondrial marker COI, has been found successful for the identification of specimens in many animal groups, but may not be suited for species discovery and delimitation if used alone. In this study, we investigate whether two observed COI haplogroups in the earthworm Aporrectodea longa correspond to two cryptic species or if the variation is intraspecific. This is done by complementing COI with two nuclear markers, ITS2 and Histone 3. The variation is studied using distance methods, parsimony networks and Bayesian coalescent trees, and the statistical distinctness of the groups is tested on gene trees using the genealogical sorting index, Rosenberg's PAB and Rodrigo et al.'s P(RD). We also applied multilocus species delimitation based on the multispecies coalescence model. The two haplogroups were found in COI, and all tests except P(RD) found them to be significantly distinct. However, in ITS2, the same groups were not recovered in any analyses or tests. H3 was invariable in A. longa, and was, therefore, included only in the multilocus analysis, which preferred a model treating A. longa as one species over a model splitting it into two. We also compared two measurements of size, body length, and no. of segments between the groups. No difference in body length was found, and although a significant difference in no. of segments was noted the haplogroup with the lower mean showed both the highest and the lowest value. When combined, these results led us to the conclusion that there is no support for the separation of A. longa into two cryptic species. This study again highlights the importance of complementing mitochondrial barcodes with more data when establishing species boundaries.}, } @article {pmid26702424, year = {2015}, author = {Ducharme, S and Albaugh, MD and Nguyen, TV and Hudziak, JJ and Mateos-Pérez, JM and Labbe, A and Evans, AC and Karama, S and , }, title = {Trajectories of cortical surface area and cortical volume maturation in normal brain development.}, journal = {Data in brief}, volume = {5}, number = {}, pages = {929-938}, pmid = {26702424}, issn = {2352-3409}, support = {N01 HD023343/HD/NICHD NIH HHS/United States ; }, abstract = {This is a report of developmental trajectories of cortical surface area and cortical volume in the NIH MRI Study of Normal Brain Development. The quality-controlled sample included 384 individual typically-developing subjects with repeated scanning (1-3 per subject, total scans n=753) from 4.9 to 22.3 years of age. The best-fit model (cubic, quadratic, or first-order linear) was identified at each vertex using mixed-effects models, with statistical correction for multiple comparisons using random field theory. Analyses were performed with and without controlling for total brain volume. These data are provided for reference and comparison with other databases. Further discussion and interpretation on cortical developmental trajectories can be found in the associated Ducharme et al.׳s article "Trajectories of cortical thickness maturation in normal brain development - the importance of quality control procedures" (Ducharme et al., 2015) [1].}, } @article {pmid26700797, year = {2016}, author = {Lu, Y and Liu, W and Tan, K and Peng, J and Zhu, Y and Wang, X}, title = {Genetic association of CALHM1 rs2986017 polymorphism with risk of Alzheimer's disease: a meta-analysis.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {37}, number = {4}, pages = {525-532}, pmid = {26700797}, issn = {1590-3478}, mesh = {Alzheimer Disease/ethnology/*genetics ; Asian People/genetics ; Calcium Channels/*genetics ; Genetic Association Studies ; *Genetic Predisposition to Disease ; Humans ; Membrane Glycoproteins/*genetics ; *Polymorphism, Single Nucleotide ; Risk ; White People/genetics ; }, abstract = {Recent studies investigating the association of Calcium homeostasis modulator 1 (CALHM1) p.P86L polymorphism (rs2986017) with Alzheimer's disease (AD) are controversial. Herein, we performed a meta-analysis to investigate the association between CALHM1 rs2986017 and AD risk. Literature searches of PubMed, Alzgene, and Embase were carried out up to 24 Nov 2015. The strength of the association between rs2986017 and AD was evaluated by odds ratio (OR) and 95 % confidence interval (CI). A total of 19 studies between 2008 and 2014 comprising 8777 AD cases and 8487 controls were included. Significant association of rs2986017 with AD was found in Caucasian population in allelic model (T vs. C: OR 1.13, 95 % CI 1.02-1.26, P = 0.022), and dominant model (TT + TC vs. CC: OR 1.15, 95 % CI 1.04-1.29, P = 0.018). No significant association was found in Asian population in any genetic model. Sensitivity analysis found that Dreses-Werringloer et al.'s might affect the overall result. The current meta-analysis suggested that CALHM1 rs2986017 might be associated with increased AD risk in Caucasian, but not Asian population.}, } @article {pmid26696219, year = {2016}, author = {Rebora, A}, title = {Trichodynia: a review of the literature.}, journal = {International journal of dermatology}, volume = {55}, number = {4}, pages = {382-384}, doi = {10.1111/ijd.13204}, pmid = {26696219}, issn = {1365-4632}, mesh = {Alopecia/*complications/epidemiology/therapy ; Humans ; Pain/*complications/epidemiology ; *Scalp ; Sex Factors ; Substance P/metabolism ; }, abstract = {Trichodynia designates a painful sensation on the scalp sometimes reported by patients with hair loss. Its best description dates back to 1960, when Sulzberger et al. (Arch Dermatol 1960; 81: 556-560) reported it in a proportion of women complaining of an unexplained diffuse alopecia. Sulzberger et al.'s remark that trichodynia may also be circumscribed ("spotty") is an important detail missed by most ensuing observers. Women are mostly affected or, at least, more likely to report it. The quality and intensity vary greatly, the "burning" variety being most severe. Whether trichodynia is prevalent in telogen effluvium or it may also be present in androgenetic alopecia remains a crucial question. Hairs shed only from painful sites, and this observation suggests that the severity of trichodynia is directly related to hair shedding and intensity. Trichodynia seems to be related to the release of substance P and is present in alopecia areata. Both observations suggest that peripilar inflammation may be a causative agent.}, } @article {pmid26669531, year = {2016}, author = {Petry, NM and Rehbein, F and Gentile, DA and Lemmens, JS and Rumpf, HJ and Mößle, T and Bischof, G and Tao, R and Fung, DS and Borges, G and Auriacombe, M and González-Ibáñez, A and Tam, P and O'Brien, CP}, title = {Griffiths et al.'s comments on the international consensus statement of internet gaming disorder: furthering consensus or hindering progress?.}, journal = {Addiction (Abingdon, England)}, volume = {111}, number = {1}, pages = {175-178}, doi = {10.1111/add.13189}, pmid = {26669531}, issn = {1360-0443}, support = {R01-AA023502/AA/NIAAA NIH HHS/United States ; P50 DA009241/DA/NIDA NIH HHS/United States ; R01 AA023502/AA/NIAAA NIH HHS/United States ; R01 AA021446/AA/NIAAA NIH HHS/United States ; P60-AA03510/AA/NIAAA NIH HHS/United States ; R01-AA021446/AA/NIAAA NIH HHS/United States ; P60 AA003510/AA/NIAAA NIH HHS/United States ; P50-DA09241/DA/NIDA NIH HHS/United States ; }, mesh = {Behavior, Addictive/*diagnosis ; *Consensus ; *Diagnostic and Statistical Manual of Mental Disorders ; Humans ; *Internationality ; Video Games/*psychology ; }, } @article {pmid26651349, year = {2016}, author = {Farr, RH and Flood, ME and Grotevant, HD}, title = {The role of siblings in adoption outcomes and experiences from adolescence to emerging adulthood.}, journal = {Journal of family psychology : JFP : journal of the Division of Family Psychology of the American Psychological Association (Division 43)}, volume = {30}, number = {3}, pages = {386-396}, pmid = {26651349}, issn = {1939-1293}, support = {R01 HD049859/HD/NICHD NIH HHS/United States ; R01-HD-049859/HD/NICHD NIH HHS/United States ; }, mesh = {Adolescent ; Adoption/*psychology ; Female ; Humans ; Longitudinal Studies ; Male ; *Sibling Relations ; Siblings/*psychology ; *Social Adjustment ; Young Adult ; }, abstract = {In many families, siblings play important roles in shaping each other's outcomes and experiences across development. In adoptive families, siblings may affect adoptees' feelings about adoption and birth family contact. Among "target adoptees" (i.e., 1 participating adopted individual within adoptive families) with siblings who may have also been adopted or the biological children of the adoptive parents, we examined how adoption experiences and individual adjustment from adolescence into emerging adulthood were associated with sibling relationship dynamics. We present 3 studies using longitudinal, mixed method data within the same overarching sample of adoptive families. Study 1 was a follow-up to Berge et al.'s (2006) study of adolescent adoptees and their adopted siblings with birth family contact; we found evidence of changes in the status of contact collectively experienced by 26 adopted sibling pairs when target adoptees were emerging adults. In Study 2, we found that target adoptees (n = 91) with siblings (adopted or not) who were more involved with target adoptees' birth family contact demonstrated more favorable behavioral outcomes than target adoptees who had uninvolved siblings. Finally in Study 3, for target adoptees with siblings who were also adopted (n = 51), results showed that target adoptees felt more positively about their own adoption when siblings expressed similar positive feelings about individual adoption experiences. Implications of our findings are discussed in terms of the enduring contributions of sibling relationships from childhood into adulthood and the unique ways in which adoptive siblings are important in shaping one another's experiences of adoption.}, } @article {pmid26649291, year = {2015}, author = {Levy, DM and Hellman, MD and Harris, JD and Haughom, B and Frank, RM and Nho, SJ}, title = {Prevalence of Cam Morphology in Females with Femoroacetabular Impingement.}, journal = {Frontiers in surgery}, volume = {2}, number = {}, pages = {61}, pmid = {26649291}, issn = {2296-875X}, abstract = {Cam and pincer are two common morphologies responsible for femoroacetabular impingement (FAI). Previous literature has reported that cam deformity is predominantly a male morphology, while being significantly less common in females. Cam morphology is commonly assessed with the alpha angle, measured on radiographs. The purpose of this study is to determine the prevalence of cam morphology utilizing the alpha angle in female subjects diagnosed with symptomatic FAI. All females presenting to the senior author's clinic diagnosed with symptomatic FAI between December 2006 and January 2013 were retrospectively reviewed. Alpha (α) angles were measured on anteroposterior and lateral (Dunn 90°, cross-table lateral, and/or frog-leg lateral) plain radiographs by two blinded physicians, and the largest measured angle was used. Using Gosvig et al.'s classification, alpha angle was characterized as (pathologic > 57°), borderline (51-56°), subtle (46-50°), very subtle (43-45°), or normal (≤42°). Three hundred and ninety-one patients (438 hips) were analyzed (age 36.2 ± 12.3 years). Among the hips included, 35.6% were normal, 14.6% pathologic, 15.1% borderline, 14.6% subtle, and 20.1% very subtle. There was no correlation between alpha angle and patient age (R = 0.17) or body mass index (R = 0.05). The intraclass correlation coefficient for α-angle measurements was 0.84. Sixty-four percent of females in this cohort had an alpha angle >42°. Subtle cam deformity plays a significant role in the pathoanatomy of female patients with symptomatic FAI. As the majority of revision hip arthroscopies are performed due to incomplete cam correction, hip arthroscopists need to be cognizant of and potentially surgically address these subtle lesions.}, } @article {pmid26648884, year = {2015}, author = {Bertels, J and Destrebecqz, A and Franco, A}, title = {Interacting Effects of Instructions and Presentation Rate on Visual Statistical Learning.}, journal = {Frontiers in psychology}, volume = {6}, number = {}, pages = {1806}, pmid = {26648884}, issn = {1664-1078}, abstract = {The statistical regularities of a sequence of visual shapes can be learned incidentally. Arciuli et al. (2014) recently argued that intentional instructions only improve learning at slow presentation rates as they favor the use of explicit strategies. The aim of the present study was (1) to test this assumption directly by investigating how instructions (incidental vs. intentional) and presentation rate (fast vs. slow) affect the acquisition of knowledge and (2) to examine how these factors influence the conscious vs. unconscious nature of the knowledge acquired. To this aim, we exposed participants to four triplets of shapes, presented sequentially in a pseudo-random order, and assessed their degree of learning in a subsequent completion task that integrated confidence judgments. Supporting Arciuli et al.'s (2014) claim, participant performance only benefited from intentional instructions at slow presentation rates. Moreover, informing participants beforehand about the existence of statistical regularities increased their explicit knowledge of the sequences, an effect that was not modulated by presentation speed. These results support that, although visual statistical learning can take place incidentally and, to some extent, outside conscious awareness, factors such as presentation rate and prior knowledge can boost learning of these regularities, presumably by favoring the acquisition of explicit knowledge.}, } @article {pmid26647724, year = {2016}, author = {Mackerras, D}, title = {Comment on Luiten et al.'s paper: 'Ultra-processed foods have the worst nutrient profile, yet they are the most available packaged products in a sample of New Zealand supermarkets'.}, journal = {Public health nutrition}, volume = {19}, number = {3}, pages = {570}, pmid = {26647724}, issn = {1475-2727}, mesh = {*Fast Foods ; New Zealand ; }, } @article {pmid26644267, year = {2017}, author = {Del Vecchio, T and Jerusalmi, D and Terjesen, MD}, title = {Psychometric characteristics of the Parenting Scale in a Vietnamese sample.}, journal = {International journal of psychology : Journal international de psychologie}, volume = {52}, number = {6}, pages = {482-490}, doi = {10.1002/ijop.12242}, pmid = {26644267}, issn = {1464-066X}, mesh = {Child ; Child, Preschool ; Factor Analysis, Statistical ; Female ; Humans ; Male ; Parenting/*trends ; Psychometrics/*methods ; Vietnam ; }, abstract = {The Parenting Scale (PS) is a well-established instrument for measuring discipline practices in Western populations. However, whether the PS is a valid and reliable measure in Eastern populations is not known. Thus, this study examined the psychometric properties of the PS in a sample of 433 Vietnamese parents of children aged 2-7 years. Confirmatory factor analyses (CFAs) examined the commonly used Reitman et al.'s two-factor and Rhoades and O'Leary's three-factor solutions. Neither factor structure fit the data. An exploratory factor analysis identified a 12-item one-factor and 14-item two-factor solutions that overlapped substantially with established factor structures. The one-factor solution reflected Lax/Overreactive parenting and the two-factor solution consisted of Lax/Overreactive and Hostile subscales. The factor structures were confirmed via multigroup CFA. Internal consistencies were acceptable and ranged between .70 and .85. Each factor was positively associated with parent anger, dysfunctional cognitions about child behaviour, and externalising child behaviour problems. However, when entered simultaneously in a regression, Hostile discipline was not uniquely associated with child behaviour. Overall, results support the potential utility of the 12-item one-factor PS as a measure of dysfunctional parenting practices for Vietnamese parents.}, } @article {pmid26640657, year = {2015}, author = {Stroud, JT and Bush, MR and Ladd, MC and Nowicki, RJ and Shantz, AA and Sweatman, J}, title = {Is a community still a community? Reviewing definitions of key terms in community ecology.}, journal = {Ecology and evolution}, volume = {5}, number = {21}, pages = {4757-4765}, pmid = {26640657}, issn = {2045-7758}, abstract = {Community ecology is an inherently complicated field, confounded by the conflicting use of fundamental terms. Nearly two decades ago, Fauth et al. (1996) demonstrated that imprecise language led to the virtual synonymy of important terms and so attempted to clearly define four keywords in community ecology; "community," "assemblage," "guild," and "ensemble". We revisit Fauth et al.'s conclusion and discuss how the use of these terms has changed over time since their review. An updated analysis of term definition from a selection of popular ecological textbooks suggests that definitions have drifted away from those encountered pre-1996, and slightly disagreed with results from a survey of 100 ecology professionals (comprising of academic professors, nonacademic PhDs, graduate and undergraduate biology students). Results suggest that confusion about these terms is still widespread in ecology. We conclude with clear suggestions for definitions of each term to be adopted hereafter to provide greater cohesion among research groups.}, } @article {pmid26640611, year = {2015}, author = {Liu, Y and Zojer, K and Lassen, B and Kjelstrup-Hansen, J and Rubahn, HG and Madsen, M}, title = {Role of the Charge-Transfer State in Reduced Langevin Recombination in Organic Solar Cells: A Theoretical Study.}, journal = {The journal of physical chemistry. C, Nanomaterials and interfaces}, volume = {119}, number = {47}, pages = {26588-26597}, pmid = {26640611}, issn = {1932-7447}, abstract = {Reduced Langevin recombination has been observed in organic solar cells (OSCs) for many years, but its origin is still unclear. A recent work by Burke et al. (Adv. Energy Mater.2015, 5, 1500123-1) was inspired by this reduced Langevin recombination, and they proposed an equilibrium model of charge-transfer (CT) states that correlates the open-circuit voltage of OSCs with experimentally available device parameters. In this work, we extend Burke et al.'s CT model further and for the first time directly correlate the reduced Langevin recombination with the energetic and dynamic behavior of the CT state. Recombination through CT states leads in a straightforward manner to a decrease in the Langevin reduction factor with increasing temperature, without explicit consideration of the temperature dependence of the mobility. To verify the correlation between the CT states and reduced Langevin recombination, we incorporated this CT model and the reduced Langevin model into drift-diffusion simulations of a bilayer OSC. The simulations not only successfully reproduced realistic current-voltage (J-V) characteristics of the bilayer OSC, but also demonstrate that the two models consistently lead to same value of the apparent Langevin reduction factor.}, } @article {pmid26626117, year = {2015}, author = {Brotman, S and Ferrer, I}, title = {Diversity Within Family Caregiving: Extending Definitions of "Who Counts" to Include Marginalized Communities.}, journal = {HealthcarePapers}, volume = {15}, number = {1}, pages = {47-53}, doi = {10.12927/hcpap.2015.24395}, pmid = {26626117}, issn = {1929-6339}, mesh = {*Aging ; *Caregivers ; Humans ; Minority Groups ; Social Work ; }, abstract = {As researchers in the field of diversity and aging, we share Williams et al.'s call for policymakers to pay attention to the experiences of family caregivers across a wider spectrum than that which currently operates in health and social care. This paper addresses the particular issues at play in interactions between caregivers from marginalized 1communities and mainstream service providers. Using case studies from our work with ethnocultural minority (2) and LGBT (3) older adults, this commentary describes the unique realities faced by marginalized communities in their efforts to both provide care and gain access to a broad range of health and social care services. The assumptions addressed provide a basis for reconsidering how caregivers are perceived, experience services and demonstrate resilience in developing alternative forms of support.}, } @article {pmid26626115, year = {2015}, author = {Keefe, J and Krawchenko, T}, title = {Taking Caregivers Seriously: An Elaboration on Research Practice.}, journal = {HealthcarePapers}, volume = {15}, number = {1}, pages = {34-39}, doi = {10.12927/hcpap.2015.24398}, pmid = {26626115}, issn = {1929-6339}, mesh = {*Caregivers ; Humans ; }, abstract = {It's time to take the needs of caregivers seriously; doing so will benefit both those providing and receiving care. This is the thrust of the argument by Williams et al. and we couldn't agree more. Our commentary offers elaboration on the sixth and final assumption - that caregivers' needs should be considered apart from cared-for persons and formal system capacity. In helping policymakers come to grips with this, we extend on Williams et al.'s argument by offering both research practices that can improve understanding of care relations and a discussion of the assessment tools that can be adopted to address the needs of the caregiver.}, } @article {pmid26611186, year = {2015}, author = {Hill, E and Solomon, Y and Dornan, T and Stalmeijer, R}, title = {'You become a man in a man's world': is there discursive space for women in surgery?.}, journal = {Medical education}, volume = {49}, number = {12}, pages = {1207-1218}, doi = {10.1111/medu.12818}, pmid = {26611186}, issn = {1365-2923}, mesh = {*Attitude of Health Personnel ; Career Choice ; Cross-Sectional Studies ; Female ; *Gender Identity ; Humans ; Physicians, Women/*psychology ; Surgeons/*psychology ; United Kingdom ; }, abstract = {CONTEXT: The UK set a target of 20% of the surgical consultant workforce to be represented by women by 2009; in 2012, it remains 7%. Studies have attributed this shortfall to the nature of careers in surgery and differing career aspirations among women.

OBJECTIVES: Rather than exploring barriers to participation, this study aims to explore the self-narratives of those women who do undertake surgical careers and who do come to see themselves as surgeons.

METHODS: The study comprises 15 individual interviews with women in surgical careers, from those aspiring to be surgeons, to senior and retired surgeons. Data were explored using discourse analysis with a priori themes derived from the literature on women in surgery and Holland et al.'s theoretical framework of Figured Worlds.

RESULTS: Discourses of being a surgeon and discourses of being a woman, existed in competition. Female surgeons figured surgery as a career requiring 100% dedication, as they did motherhood, although the demands of the two roles differed and consequently the roles were not discursively compatible. Many related powerfully negative experiences in which their gender had marked them out as 'other' within surgery. Women described how they were expected to show masculine traits as surgeons and the ways to consequently become legitimate in the surgical world as a 'woman surgeon'. They found creative ways to articulate how women in general, and feminine qualities in particular, enhanced surgery. Finally, some women engaged in identity work, termed 'world making', - the creative orchestration of discourses of surgeonhood and motherhood to be mutually sustaining.

CONCLUSIONS: There is little discursive space in which to be both a successful woman and a successful surgeon. Those who combine these roles must either be innovative in refiguring what it means to be a woman or what it means to be a surgeon, or they must author a new space for themselves, a powerful discursive process termed 'world making'.}, } @article {pmid26594188, year = {2015}, author = {Cheng, X and Ge, H and Andoni, D and Ding, X and Fan, Z}, title = {Composite body movements modulate numerical cognition: evidence from the motion-numerical compatibility effect.}, journal = {Frontiers in psychology}, volume = {6}, number = {}, pages = {1692}, pmid = {26594188}, issn = {1664-1078}, abstract = {A recent hierarchical model of numerical processing, initiated by Fischer and Brugger (2011) and Fischer (2012), suggested that situated factors, such as different body postures and body movements, can influence the magnitude representation and bias numerical processing. Indeed, Loetscher et al. (2008) found that participants' behavior in a random number generation task was biased by head rotations. More small numbers were reported after leftward than rightward head turns, i.e., a motion-numerical compatibility effect. Here, by carrying out two experiments, we explored whether similar motion-numerical compatibility effects exist for movements of other important body components, e.g., arms, and for composite body movements as well, which are basis for complex human activities in many ecologically meaningful situations. In Experiment 1, a motion-numerical compatibility effect was observed for lateral rotations of two body components, i.e., the head and arms. Relatively large numbers were reported after making rightward compared to leftward movements for both lateral head and arm turns. The motion-numerical compatibility effect was observed again in Experiment 2 when participants were asked to perform composite body movements of congruent movement directions, e.g., simultaneous head left turns and arm left turns. However, it disappeared when the movement directions were incongruent, e.g., simultaneous head left turns and arm right turns. Taken together, our results extended Loetscher et al.'s (2008) finding by demonstrating that their effect is effector-general and exists for arm movements. Moreover, our study reveals for the first time that the impact of spatial information on numerical processing induced by each of the two sensorimotor-based situated factors, e.g., a lateral head turn and a lateral arm turn, can cancel each other out.}, } @article {pmid26582897, year = {2015}, author = {Steinman, L and Ahmed, SS}, title = {Response to comment on "Antibodies to influenza nucleoprotein cross-react with human hypocretin receptor 2".}, journal = {Science translational medicine}, volume = {7}, number = {314}, pages = {314lr2}, doi = {10.1126/scitranslmed.aad6789}, pmid = {26582897}, issn = {1946-6242}, mesh = {Antibodies, Viral/*immunology ; Cross Reactions/*immunology ; Humans ; Orexin Receptors/*immunology ; RNA-Binding Proteins/*immunology ; Viral Core Proteins/*immunology ; }, abstract = {Vassalli et al.'s study does not involve or provide additional data regarding influenza virus, influenza vaccines, human samples, animal models of narcolepsy, or experiments related to mimicry and cross-reactivity. They present data on the distribution of hypocretin (HCRT) (also known as orexin) receptors in the brain of an engineered mouse developed by them.}, } @article {pmid26582896, year = {2015}, author = {Vassalli, A and Li, S and Tafti, M}, title = {Comment on "Antibodies to influenza nucleoprotein cross-react with human hypocretin receptor 2".}, journal = {Science translational medicine}, volume = {7}, number = {314}, pages = {314le2}, doi = {10.1126/scitranslmed.aad2353}, pmid = {26582896}, issn = {1946-6242}, mesh = {Antibodies, Viral/*immunology ; Cross Reactions/*immunology ; Humans ; Orexin Receptors/*immunology ; RNA-Binding Proteins/*immunology ; Viral Core Proteins/*immunology ; }, abstract = {Did hypocretin receptor 2 autoantibodies cause narcolepsy with hypocretin deficiency in Pandemrix-vaccinated children, as suggested by Ahmed et al.? Using newly developed mouse models to report and inactivate hypocretin receptor expression, Vassalli et al. now show that hypocretin neurons (whose loss causes narcolepsy) do not express hypocretin autoreceptors, raising questions to the interpretation of Ahmed et al.'s findings.}, } @article {pmid26580963, year = {2015}, author = {Alizadeh, M and Zamani, M and Baharun, S and Abdul Manaf, A and Sakurai, K and Anada, H and Keshavarz, H and Ashraf Chaudhry, S and Khurram Khan, M}, title = {Cryptanalysis and Improvement of "A Secure Password Authentication Mechanism for Seamless Handover in Proxy Mobile IPv6 Networks".}, journal = {PloS one}, volume = {10}, number = {11}, pages = {e0142716}, pmid = {26580963}, issn = {1932-6203}, mesh = {Cell Phone ; *Computer Communication Networks ; *Computer Security ; Humans ; *Internet ; *Telemedicine ; }, abstract = {Proxy Mobile IPv6 is a network-based localized mobility management protocol that supports mobility without mobile nodes' participation in mobility signaling. The details of user authentication procedure are not specified in this standard, hence, many authentication schemes have been proposed for this standard. In 2013, Chuang et al., proposed an authentication method for PMIPv6, called SPAM. However, Chuang et al.'s Scheme protects the network against some security attacks, but it is still vulnerable to impersonation and password guessing attacks. In addition, we discuss other security drawbacks such as lack of revocation procedure in case of loss or stolen device, and anonymity issues of the Chuang et al.'s scheme. We further propose an enhanced authentication method to mitigate the security issues of SPAM method and evaluate our scheme using BAN logic.}, } @article {pmid26571348, year = {2016}, author = {Kennedy, P and Kilvert, A and Hasson, L}, title = {A 21-year longitudinal analysis of impact, coping, and appraisals following spinal cord injury.}, journal = {Rehabilitation psychology}, volume = {61}, number = {1}, pages = {92-101}, doi = {10.1037/rep0000066}, pmid = {26571348}, issn = {1939-1544}, mesh = {*Adaptation, Psychological ; Adolescent ; Adult ; Aged ; Anxiety Disorders/complications/*psychology ; *Attitude to Health ; Cohort Studies ; Depressive Disorder/complications/*psychology ; Female ; Follow-Up Studies ; Humans ; Longitudinal Studies ; Male ; Middle Aged ; Spinal Cord Injuries/complications/*psychology/rehabilitation ; Stress, Psychological/complications/*psychology ; Young Adult ; }, abstract = {OBJECTIVES: To examine mortality, psychological impact, coping strategies, and cognitive appraisals in a cohort of individuals with spinal cord injury from 12 weeks postinjury to >21 years post-hospital discharge.

METHOD: This longitudinal, multiple-wave panel study accounted for 50.6% of Kennedy et al.'s (2000) original cohort. Twenty-two participants consented to take part in the current study, and data were collected from the COPE, Beck Depression Inventory, Functional Independence Measure, and a new measure of appraisal: Appraisals of DisAbility: Primary and Secondary Scale (ADAPSS). A further 22 individuals were deceased, giving a total sample of 44 for examining longitudinal factors in relation to mortality.

RESULTS: The 22 deceased individuals were found to have significantly higher depression and anxiety at Week 12 than the 22 individuals who participated in the current study. There were significant increases in use of "positive" coping strategies and significant decreases in "negative" strategies. A significant regression model found coping strategies at Week 12 predicted 37% of variance in depression at 21-plus years. Depression and coping strategies at Week 12 were found to predict variance in cognitive appraisals at 21 years.

CONCLUSIONS: The findings suggest that psychological factors, such as depression, and aspects of coping strategies may contribute to premature mortality. Further research is needed to develop interventions that focus on protective psychological factors to reduce mortality risk following SCI. Coping strategies in the early stages of rehabilitation are an important predictor of both long-term psychological outcomes and appraisals, and this has clinical implications for psychological aspects of rehabilitation.}, } @article {pmid26571288, year = {2015}, author = {Aagaard, H and Uhrenfeldt, L and Spliid, M and Fegran, L}, title = {Parents' experiences of transition when their infants are discharged from the Neonatal Intensive Care Unit: a systematic review protocol.}, journal = {JBI database of systematic reviews and implementation reports}, volume = {13}, number = {10}, pages = {123-132}, doi = {10.11124/jbisrir-2015-2287}, pmid = {26571288}, issn = {2202-4433}, mesh = {Adult ; Clinical Protocols ; Female ; Humans ; Infant, Newborn ; Infant, Premature/*psychology ; *Intensive Care Units, Neonatal ; Intensive Care, Neonatal/*psychology ; Kangaroo-Mother Care Method/psychology ; Male ; Parents/*psychology ; Patient Discharge ; Qualitative Research ; Systematic Reviews as Topic ; *Transitional Care ; }, abstract = {REVIEW QUESTION/OBJECTIVE: The objective of this review is to identify, appraise and synthesize the best available studies exploring parents' experiences of transition when their infants are discharged from the Neonatal Intensive Care Unit (NICU).The review questions are:

BACKGROUND: Giving birth to a premature or sick infant is a stressful event for parents. The parents' presence and participation in the care of the infant is fundamental to reduce this stress and to provide optimal care for both the premature or sick infant and family. A full term pregnancy is estimated to last between 37 and 40 weeks. Preterm infants born before 28 week (5.1%) are defined as extremely preterm, while those who are born between 28 to 31 weeks (10.3%) are defined as very preterm. The majority of the preterm (84.1%) are born between 32 to 37 week and may have significant medical problems requiring prolonged hospitalization.The prevalence of preterm birth is increasing worldwide. More than one in ten babies are born preterm annually. This is equal to 15 million preterm infants born globally and the second largest direct cause of deaths in children below five. The highest rates of preterm birth are in Sub-Saharan Africa and South Asia (more than 60%) and the lowest rates are in Northern Africa, Western Asia, Latin America and the Caribbean. The preterm birth rates in the developing countries vary widely and follow a different pattern than in high income countries.The preterm birth rate has increased between 1990 and 2010 with an average of 0.8% annually in almost all countries. Morbidity among critically ill newborn and preterm infants vary widely from no late effects to severe complications, such as visual or hearing impairment, chronic lung disease, growth failure in infancy and specific learning impairments, dyslexia and reduced academic achievement. Full term infants may also experience significant health problems requiring neonatal intensive care. The most common reasons for a full term infant to be admitted to a NICU after birth are temperature instability, hypoglycemia, respiratory distress, hyperbilirubinemia and neonatal mortality. Admission of a full term newborn infant from home within the first four weeks after birth is due to jaundice, dehydration, respiratory complications, feeding difficulties, urinary tract infection, diarrhea and meningitis.In the last two to three decades, technological advances in neonatalogy have improved the survival rates of critically ill and preterm infants.Two major issues have influenced the design of the NICU wards: i) the increased volume of preterm infants with extremely low gestational age who need neonatalogy assistance, and ii) the impact of the parents' presence in the NICU to support the infant's development.The health status of preterm babies can have a significant impact on the family wellbeing and function. The separation between the preterm infant and the parents is a threat to the attachment and bonding process. Worldwide, there has been a paradigm shift in the NICUs over the last decade, inviting parents to be admitted together with the infant or at least to spend most of the day together with their critical ill and preterm infant in the NICU. Parental involvement increases the performing of Kangaroo Mother Care during the admission in the NICU and increases parental preparedness for discharge to home. This change prepares the parents to take over tasks such as nurturing and feeding. The parents are the most important caregivers for the infant during the admission in the NICU and their co-admission increases the bonding and prepare the parents for the transition discharged to home.Family centered care (FCC) based on a partnership between families and professionals is described as essential in current research on neonatal care. Family centered care is facilitated by parental involvement, communication based on mutuality and respect, and unrestricted parental presence in the NICU. According to Mikkelsen and Frederiksen, the central attribute of FCC is partnership with the core value of mutuality and common goals.A NICU is a high-tech setting where highly specialized professionals care for premature or critically ill infants. During the infants' hospitalization, the relationship between parents and nurses evolves through an interchange of roles and responsibilities. However, this collaboration is challenging due to a discrepancy between parents' and nurses' expectations of their roles.To facilitate parents' skin-to-skin contact and involvement in their infant's care, NICUs are now redesigned to facilitate parents' "24-hour" presence, also called "rooming-in". Seporo et al. describes several benefits with "rooming-in" the NICUs. Staying in the same room increases infants' and parents' possibility for "skin-to-skin care". This improves the infant's sleep time and temperature regulation, decreased crying and need for oxygen, increases parental confidence and positive infant-parent interaction. Parents' experience of "skin-to-skin care" and "rooming in" may help parents to be acquainted with their infant and thus prepare for the transition to home. However, despite these positive effects of rooming-in, some negative effects, e.g. less sleep and lack of privacy, have been described by parents who have stayed with their child in a pediatric unit.The hospitalization may challenge the normal attachment process and parents' confidence as caregivers; parents' preparation for bringing the infant home is thus essential. The infant's discharge from the NICU is experienced as a moment of mixed feelings. Going home is a happy event, but at the same time it is combined with parental anxiety. Parents' pervasive uncertainty, medical concerns and adjustment to the new parental and partner-adjustment role are common concerns. To make parents confident and prepared for taking their infant home tailored information, guidance and hands-on experience caring for their infant before discharge is crucial.During the literature research we became aware of a systematic narrative review protocol by Parascandolo et al.'s concerning nurses', midwives', doctors' and parents' experiences of the preterm infants' discharge to home. The aim of our comprehensive review is to perform a metasynthesis on parents' perspectives and their experiences of transition from discharge from NICU to home. We will include qualitative primary studies to offer a deeper understanding of the parent perspective.}, } @article {pmid26571280, year = {2015}, author = {Skar, P and Young, L and Gordon, C}, title = {Changes in blood pressure among users of lay health worker or volunteer operated community-based blood pressure programs over time: a systematic review protocol.}, journal = {JBI database of systematic reviews and implementation reports}, volume = {13}, number = {10}, pages = {30-40}, doi = {10.11124/jbisrir-2015-1927}, pmid = {26571280}, issn = {2202-4433}, mesh = {Adult ; Blood Pressure/*physiology ; Blood Pressure Monitoring, Ambulatory/methods ; Clinical Protocols ; Community Health Services/*methods ; Community Health Workers ; Female ; Humans ; Hypertension/physiopathology/*therapy ; Male ; Middle Aged ; Program Evaluation/*methods ; Systematic Reviews as Topic ; Time Factors ; }, abstract = {REVIEW QUESTION/OBJECTIVE: The objective of this review is to identify studies reporting on lay health worker- or volunteer-led community-based programs for blood pressure screening and cardiovascular awareness in order to determine if these programs contribute to changes in blood pressure among participants over time.The specific question for this review is: What are the changes in blood pressure among adult users of community-based blood pressure screening and awareness programs operated by lay health workers or volunteers as measured by the differences in systolic and diastolic blood pressure between the user's first visit to the program and their last visit to the program?

BACKGROUND: Cardiovascular diseases, such as stroke and heart disease, are quickly becoming global diseases manifesting in countries and communities where they traditionally had not been widespread. The World Health Organization (WHO) has reported that "in the Asia/Pacific region, [cardiovascular disease] has become increasingly prevalent in recent decades, and now accounts for about one third of all deaths". One risk factor that can lead to cardiovascular disease is hypertension. Based on WHO data from 2008, hypertension is now a global problem affecting 27% of the population 25 years of age or older.The risk for cardiovascular disease also appears to be higher among people in urban areas. A recent United Nations population report indicates that in the next 40 years we could see an increase in the world's population by 2.3 billion people. The majority of these people will be residing in urban areas, particularly in developing nations. Between 2011 and 2050, "the population living in urban areas is projected to gain 2.6 billion, passing from 3.6 billion in 2011 to 6.3 billion in 2050". Population growth in urban areas is therefore not only projected to include the expected population growth but also expected to include a shift of rural population to urban centers and "most of the population growth expected in urban areas will be concentrated in the cities and towns of the less developed regions". This growth of urban areas has the potential to put enormous pressures on health care systems that are already struggling to cope with the rapid increase in diseases thought to be more prevalent in Western societies, such as cardiovascular diseases.Hypertension may be difficult to treat due to a number of factors. Globally, access to antihypertensive medications, hypertension screening, and access to medical care vary from one country to another. Lifestyle factors, such as salt and alcohol consumption, stress, smoking, body weight, and exercise, are risk factors for hypertension that may be influenced by culture, which can in turn support or hinder lifestyle decisions that could significantly affect blood pressure. Hypertension, however, is easy to detect. A trained person with access to a low-cost sphygmomanometer can detect abnormal blood pressures quickly; however, access to trained personnel is not universally guaranteed. Globally - according to one model of skilled health care worker density and total requirement offered for discussion by the Global Health Workforce Alliance and WHO - there could currently be an estimated shortage of over seven million skilled health care workers (midwifes, nurses and physicians), as measured against a theoretical density of skilled health care workers to population. The shortage of skilled health care workers in this model could grow to over 12 million by 2035 if the assumptions of the model and population growth estimates are valid. Through rapid urbanization the potential for inequities in access to healthcare is also increased.Over the last few years, a number of community-based blood pressure screening and education initiatives have been established. These initiatives have been created either as part of research, as part of community outreach programs by publicly funded agencies, or as part of an outreach by not-for-profit organizations with a particular interest in reducing cardiovascular disease in specific hard-to-reach populations. Several systematic reviews have been conducted to assess different models for delivering services to people living with high blood pressure to assess community-based programs with a focus on cardiovascular disease, and to assess effectiveness of community health workers (CHW) in a variety of settings. These systematic reviews point to the importance of distinguishing between different categories of health care providers, their training and their roles in program delivery when assessing studies for possible inclusion in a systematic review.In a systematic review of studies from the US by Brownstein et al. focusing on the effectiveness of community health workers (CHWs) in the care of people with hypertension, this category of health care providers went under many different names. Community health workers in this review were defined as "any health workers who carried out functions related to health care deliver, were trained as part of an intervention, had no formal paraprofessional or professional designation, and had a relationship with the community being served". One of the findings from this review was the wide variety of formal training of the CHWs. In other parts of the world, a CHW might be defined differently. In their review of CHW-based programs focusing on children's health, Bhattacharyya, Winch, LeBan and Tien found that "in general CHWs are not paid salaries because the MOH (Ministry of Health) or donors do not consider salaries to be sustainable. Yet CHWs are often held accountable and supervised as if they were employees. Community health worker programs must recognize that CHWs are volunteers (emphasis in original), even if they receive small monetary or nonmonetary incentives. They are volunteering their time to serve the community". One Canadian model for delivering a cardiovascular awareness program designed to reach older adults through their primary care provider is based on volunteers with basic training to perform blood pressure measurements and cardiovascular health information.In a global review of a wide range of public health and health promotion initiatives operated by lay health workers from 2005, Lewin et al. identified over 40 different names or terms for a lay health worker. However, the definition of a lay health worker used by Lewin et al. is very similar to the definition of CHWs offered by Brownstein et al. Lewin et al.'s systematic review was the only study with a global focus that was located that reviewed studies of programs with a cardiovascular component using lay health workers. In this study, the sample size of studies focusing on lay health workers and cardiovascular disease was small (N=3) and the results from two of the studies were inconclusive to the point where the authors felt they could not pool the results.While a lay health worker may or may not receive some compensation for their work, volunteers in higher income areas of the world such as in North America typically do not receive any compensation. Volunteers, as observed by Bhattacharyya et al., are common in many parts of the world, and in some areas they provide delivery of programs and services that reach hundreds of thousands of individuals. One challenge for this systematic review will therefore be to isolate those programs that are delivered by lay health workers or volunteers who receive little or no compensation and programs where staff is paid. The importance of this distinction is on one hand related to cost - as observed by Bhattacharyya et al., many organizations responsible for delivery of community-based programs do not have funding for salaried staff. On the other hand there might be other factors in the relationship between a community being served by a program and the staff delivering the program. One such factor could be linked to the role of the person delivering the program as either a paid health care professional or an unpaid lay health worker or volunteer.Through this proposed JBI systematic review, the reviewers will focus on community-based blood pressure screening and health information programs delivered by either lay health workers or volunteers. Previous systematic reviews have indicated that programs focusing on blood pressure reduction delivered in a variety of settings and delivered by a variety of health care professionals might lower blood pressure among program participants over time. This systematic review will be limited to community-based programs rather than hospital or research facility-based programs, and to programs delivered by lay health workers or volunteers rather than programs delivered by paid community health workers, nurses or teams of health care providers under direction of a primary care provider. Compared to other recent systematic reviews which focused on studies with comparison groups and included few studies where lay health workers were involved, this systematic review will attempt to fill this gap in knowledge about programs delivered by lay health workers or volunteers by focusing on non-randomized controlled studies which report blood pressure changes over time in programs targeting the general population. Community-based programs might have a variety of designs with a number of different interventions, and where possible these designs and interventions will be identified and subgroup analysis conducted as appropriate. It is hoped that this systematic review can extend the work by Lewin et al. by identifying additional studies globally, focusing on programs delivered by lay health workers or volunteers but limited to studies reporting changes in blood pressure over time. Where possible, a meta-analysis of the changes in blood pressure over time among participants in these programs will be conducted. (ABSTRACT TRUNCATED)}, } @article {pmid26565369, year = {2015}, author = {Alastuey, A and Ballenegger, V and Ebeling, W}, title = {Comment on "Direct linear term in the equation of state of plasmas".}, journal = {Physical review. E, Statistical, nonlinear, and soft matter physics}, volume = {92}, number = {4}, pages = {047101}, doi = {10.1103/PhysRevE.92.047101}, pmid = {26565369}, issn = {1550-2376}, abstract = {In a recent paper [Phys. Rev. E 91, 013108 (2015)], Kraeft et al. criticize known exact results on the equation of state of quantum plasmas, which have been obtained independently by several authors. They argue about a difference in the definition of the direct two-body function Q(x), which appears in virial expansions of thermodynamical quantities, but Q(x) is not a measurable quantity in itself. Differences in definitions of intermediate quantities are irrelevant, and only differences in physical quantities are meaningful. Beyond Kraeft et al.'s broad statement that there is no agreement at order ρ(5/2) in the virial equation for the pressure, we show that their published results for this quantity are in fact in perfect agreement with previous existing expressions.}, } @article {pmid26565226, year = {2015}, author = {Yamamoto, K and Hatano, N}, title = {Thermodynamics of the mesoscopic thermoelectric heat engine beyond the linear-response regime.}, journal = {Physical review. E, Statistical, nonlinear, and soft matter physics}, volume = {92}, number = {4}, pages = {042165}, doi = {10.1103/PhysRevE.92.042165}, pmid = {26565226}, issn = {1550-2376}, abstract = {Mesoscopic thermoelectric heat engine is much anticipated as a device that allows us to utilize with high efficiency wasted heat inaccessible by conventional heat engines. However, the derivation of the heat current in this engine seems to be either not general or described too briefly, even inappropriately in some cases. In this paper, we give a clear-cut derivation of the heat current of the engine with suitable assumptions beyond the linear-response regime. It resolves the confusion in the definition of the heat current in the linear-response regime. After verifying that we can construct the same formalism as that of the cyclic engine, we find the following two interesting results within the Landauer-Büttiker formalism: the efficiency of the mesoscopic thermoelectric engine reaches the Carnot efficiency if and only if the transmission probability is finite at a specific energy and zero otherwise; the unitarity of the transmission probability guarantees the second law of thermodynamics, invalidating Benenti et al.'s argument in the linear-response regime that one could obtain a finite power with the Carnot efficiency under a broken time-reversal symmetry [Phys. Rev. Lett. 106, 230602 (2011)]. These results demonstrate how quantum mechanics constrains thermodynamics.}, } @article {pmid26553217, year = {2016}, author = {Santos Filho, CA and Tirico, PP and Stefano, SC and Touyz, SW and Claudino, AM}, title = {Systematic review of the diagnostic category muscle dysmorphia.}, journal = {The Australian and New Zealand journal of psychiatry}, volume = {50}, number = {4}, pages = {322-333}, doi = {10.1177/0004867415614106}, pmid = {26553217}, issn = {1440-1614}, mesh = {Body Dysmorphic Disorders/*diagnosis/psychology ; Body Image/*psychology ; Humans ; *Muscle, Skeletal ; }, abstract = {OBJECTIVES: (1) To collect, analyze and synthetize the evidence on muscle dysmorphia diagnosis as defined by Pope et al. and (2) To discuss its appropriate nosology and inclusion as a specific category in psychiatric classificatory systems.

METHOD: A systematic search in the MEDLINE, the PsycNET, the LILACS and SciELO databases and in the International Journal of Eating Disorders was conducted looking for articles published between January 1997 and October 2014 and in EMBASE database between January 1997 and August 2013. Only epidemiological and analytical studies were considered for selection. The methodological quality of included studies was assessed according to the Evidence-Based Mental Health and the National Health and Medical Research Council's guidelines. The support for inclusion of muscle dysmorphia in psychiatric classificatory systems was examined against Blashfield et al.'s criteria.

RESULTS: Thirty-four articles were considered eligible out of 5136. Most of the studies were cross-sectional and enrolled small, non-clinical samples. The methodological quality of all selected papers was graded at the lowest hierarchical level due to studies' designs. Forty-one percent of the publications considered the available evidence insufficient to support the inclusion of muscle dysmorphia in any existing category of psychiatric disorders. The current literature does not fulfill Blashfield et al.'s criteria for the inclusion of muscle dysmorphia as a specific entity in psychiatric diagnostic manuals.

CONCLUSION: The current evidence does not ensure the validity, clinical utility, nosological classification and inclusion of muscle dysmorphia as a new disorder in classificatory systems of mental disorders.}, } @article {pmid26541052, year = {2015}, author = {Cecchetto, S and Lawson, R}, title = {Simultaneous Sketching Aids the Haptic Identification of Raised Line Drawings.}, journal = {Perception}, volume = {44}, number = {7}, pages = {743-754}, doi = {10.1177/0301006615594695}, pmid = {26541052}, issn = {0301-0066}, mesh = {Cues ; Discrimination Learning ; Humans ; *Pattern Recognition, Physiological ; *Pattern Recognition, Visual ; Perceptual Distortion ; Physical Stimulation/methods ; Reaction Time ; *Touch ; }, abstract = {Haptically identifying raised line drawings is difficult. We investigated whether a major component of this difficulty lies in acquiring, integrating, and maintaining shape information from touch. Wijntjes, van Lienen, Verstijnen, and Kappers reported that drawings which participants had failed to identify by touch alone could often subsequently be named if they were sketched. Thus, people sometimes needed to externalize haptically acquired information by making a sketch in order to be able to use it. We extended Wijntjes et al.'s task and found that sketching while touching improved drawing identification even more than sketching after touching, but only if people could see their sketches. Our results suggest that the slow, serial nature of information acquisition seriously hampers the haptic identification of raised line drawings relative to visually identifying line drawings. Simultaneous sketching may aid identification by reducing the burden on working memory and by helping to guide haptic exploration. This conclusion is consistent with the finding reported by Lawson and Bracken that 3-D objects are much easier to identify haptically than raised line drawings since, unlike for vision, simultaneously extracting global shape information is much easier haptically for 3-D stimuli than for line drawings.}, } @article {pmid26537952, year = {2016}, author = {Yang, W and Sun, Y}, title = {A monolingual mind can have two time lines: Exploring space-time mappings in Mandarin monolinguals.}, journal = {Psychonomic bulletin & review}, volume = {23}, number = {3}, pages = {857-864}, pmid = {26537952}, issn = {1531-5320}, mesh = {Adult ; China ; *Cognition ; Female ; Humans ; *Language ; Male ; Metaphor ; Middle Aged ; *Time ; }, abstract = {Can a mind accommodate two time lines? Miles, Tan, Noble, Lumsden and Macrae (Psychonomic Bulletin & Review 18, 598-604, 2011) shows that Mandarin-English bilinguals have both a horizontal space-time mapping consistent with linguistic conventions within English and a vertical representation of time commensurate with Mandarin. However, the present study, via two experiments, demonstrates that Mandarin monolinguals possess two mental time lines, i.e., one horizontal and one vertical line. This study concludes that a Mandarin speaker has two mental time lines not because he/she has acquired L2 English, but because there are both horizontal and vertical expressions in Mandarin spatiotemporal metaphors. Specifically, this study highlights the fact that a horizontal time line does exist in a Mandarin speaker's cognition, even if he/she is a Mandarin monolingual instead of a ME bilingual. Taken together, the evidence in hand is far from sufficient to support Miles et al.'s (2011) conclusion that ME bilinguals' horizontal concept of time is manipulated by English. Implications for theoretical issues concerning the language-thought relationship in general and the effect of bilingualism on cognition in particular are discussed.}, } @article {pmid26534851, year = {2015}, author = {Young, RA}, title = {Driver Compensation: Impairment or Improvement?.}, journal = {Human factors}, volume = {57}, number = {8}, pages = {1334-1338}, doi = {10.1177/0018720815585053}, pmid = {26534851}, issn = {1547-8181}, mesh = {Accidents, Traffic ; *Attention ; Automobile Driving/psychology ; Humans ; Reaction Time ; *User-Computer Interface ; }, abstract = {Strayer et al.'s conclusion that their "cognitive distraction scale" for auditory-vocal tasks indicates "significant impairments to driving" is not supported by their data. Additional analysis demonstrates that slower brake reaction times during auditory-vocal tasks were fully compensated for by longer following distances to the lead car. Naturalistic driving data demonstrate that cellular conversation decreases crash risk, the opposite of the article's assumption. Hence, the scale's internal and external validities for indicating driving impairment are highly questionable.}, } @article {pmid26534849, year = {2015}, author = {Shinar, D}, title = {Cognitive Workload ≠ Crash Risk: Rejoinder to Study by Strayer et al. (2015).}, journal = {Human factors}, volume = {57}, number = {8}, pages = {1328-1330}, doi = {10.1177/0018720815574943}, pmid = {26534849}, issn = {1547-8181}, mesh = {Accidents, Traffic ; Automobile Driving/*psychology ; Cognition ; Humans ; *Safety ; Work ; Workload/psychology ; }, abstract = {Strayer et al.'s article is a significant attempt to scale the cognitive workload of different potentially distracting tasks. It is tempting but not warranted to equate the workload with the relative risk of crash involvement. In this article, I list the reasons why the scaling should not be generalized to safety implications in real driving and argue for the combination of studies of maximal performance assessment (e.g., simulation) with behavioral assessment (e.g., naturalistic driving).}, } @article {pmid26511765, year = {2016}, author = {Leibovitz, Z and Daniel-Spiegel, E and Malinger, G and Haratz, K and Tamarkin, M and Gindes, L and Schreiber, L and Ben-Sira, L and Lev, D and Shapiro, I and Bakry, H and Weizman, B and Zreik, A and Egenburg, S and Arad, A and Tepper, R and Kidron, D and Lerman-Sagie, T}, title = {Prediction of microcephaly at birth using three reference ranges for fetal head circumference: can we improve prenatal diagnosis?.}, journal = {Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology}, volume = {47}, number = {5}, pages = {586-592}, doi = {10.1002/uog.15801}, pmid = {26511765}, issn = {1469-0705}, mesh = {Cephalometry/*methods ; Female ; Gestational Age ; Humans ; Medical Overuse/statistics & numerical data ; Microcephaly/*diagnosis ; Pregnancy ; Prenatal Diagnosis/*methods ; Sensitivity and Specificity ; Ultrasonography, Prenatal/*methods ; }, abstract = {OBJECTIVE: To evaluate the prediction of microcephaly at birth (micB) using established and two new reference ranges for fetal head circumference (HC) and to assess whether integrating additional parameters can improve prediction.

METHODS: Microcephaly in utero was defined as a fetal HC 3SD below the mean for gestational age according to Jeanty et al.'s reference range. The records of cases with fetal microcephaly (Fmic) were evaluated for medical history, imaging findings, biometry and postnatal examination/autopsy findings. Microcephaly was confirmed at birth (micB) by an occipitofrontal circumference (OFC) or a brain weight at autopsy 2SD below the mean for gestational age. The new INTERGROWTH-21(st) Project and a recent Israeli reference for fetal growth were applied for evaluation of the Fmic positive predictive value (PPV) for diagnosis of micB cases. Optimal HC cut-offs were determined for each of the new references with the aim of detecting all micB cases whilst minimizing the number of false positives found to have a normal HC at birth. We also assessed the difference between the Z-scores of the prenatal HC and the corresponding OFC at birth, the frequency of small-for-gestational age (SGA), decreased HC/abdominal circumference (AC) and HC/femur length (FL) ratios, the prevalence of associated malformations and family history.

RESULTS: Forty-two fetuses were diagnosed as having Fmic according to the Jeanty reference, but micB was confirmed in only 24 (PPV, 57.1%). The optimal INTERGROWTH and Israeli reference HC cut-offs for micB diagnosis were mean - 3SD and mean - 2.3SD, resulting in a statistically non-significant improvement in PPV to 61.5% and 66.7%, respectively. The presence of a family history of microcephaly, SGA, associated malformations and application of stricter HC cut-offs resulted in a higher PPV of micB, although not statistically significant and with a concurrent increase in the number of false-negative results. The deviation of the HC from the mean, by all references, was significantly larger compared with the actual deviation of the OFC at birth, with mean differences between the corresponding Z-scores of -1.15, -1.95 and -0.74 for the Jeanty, INTERGROWTH and Israeli references, respectively.

CONCLUSIONS: The evaluated reference ranges all result in considerable over-diagnosis of fetal microcephaly. The use of the two new HC reference ranges did not significantly improve micB prediction compared with that of Jeanty et al., whilst use of additional characteristics and stricter HC cut-offs could improve the PPV with an increase in false negatives. The postnatal OFC deviates significantly less from the mean compared with the prenatal HC, and we propose that adjustment for this would enable better prediction of the actual OFC deviation at birth. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.}, } @article {pmid26499125, year = {2016}, author = {Arráez-Aybar, LA and Fuentes-Redondo, T and Millán, JM}, title = {Persistent trigeminal artery: a cross-sectional study based on over 3 years conventional angiography, CT angiography and MR angiography images.}, journal = {Surgical and radiologic anatomy : SRA}, volume = {38}, number = {4}, pages = {445-453}, pmid = {26499125}, issn = {1279-8517}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Anatomic Variation ; Carotid Artery, Internal/*abnormalities ; Cerebrovascular Disorders/etiology ; Computed Tomography Angiography ; Cross-Sectional Studies ; Female ; Humans ; Magnetic Resonance Angiography ; Male ; Middle Aged ; Young Adult ; }, abstract = {PURPOSE: The trigeminal artery is one of the four primitive anastomosis established between the internal carotid artery and the vertebrobasilar system that regresses at the sixth week of embryonic development. Its persistence in adult life (PTA) is usually found incidentally. The aim of this study is to determine its prevalence, main characteristics and clinical significance.

METHODS: A cross-sectional study was performed over the last 3 years, 2012-2014, to analyze images performed on conventional angiography, CT angiography and MR angiography of patients who attended the Neuroradiology Department of the Hospital Universitario Doce de Octubre in Madrid, Spain, to control their underlying pathology.

RESULTS: Nine cases of PTA were found (prevalence 0.37 %, two men, seven women; three right, six left; age range 13-88 years). Eight PTA emerged from the cavernous ICA and one from the petrous segment. Six cases were lateral or petrosal type and one was medial or sphenoidal type. The whole PTAs anastomosed the BA, six at the middle third and three at the distal third. Weon et al.'s type 3 was predominant. CVD incidence was 55.6 % and aneurysm incidence was 22 %.

CONCLUSIONS: PTA prevalence was similar to those previously reported, being commonly left-sided, Salas et al.'s lateral or petrosal type, Weon et al.'s type 3 and with no gender predominance. CVD and aneurysms incidence in the presence of a PTA were higher than in general population. Its anatomical relations make it essential to consider its presence and directional blood flow when planning endovascular and neurosurgical treatments.}, } @article {pmid26487342, year = {2015}, author = {Westreich, D and Edwards, JK}, title = {Invited commentary: every good randomization deserves observation.}, journal = {American journal of epidemiology}, volume = {182}, number = {10}, pages = {857-860}, pmid = {26487342}, issn = {1476-6256}, support = {DP2 HD084070/HD/NICHD NIH HHS/United States ; DP2HD084070/DP/NCCDPHP CDC HHS/United States ; }, mesh = {Anti-HIV Agents/*administration & dosage ; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination/*administration & dosage ; Female ; HIV Infections/*prevention & control ; Humans ; Male ; Pre-Exposure Prophylaxis/*methods ; *Research Design ; *Assessment of Medication Adherence ; }, abstract = {Preexposure prophylaxis (PrEP) is a promising approach to prevention of human immunodeficiency virus (HIV) transmission, in which an HIV-negative individual takes a single daily dose of an antiretroviral drug so that, if exposed to HIV, an active antiretroviral drug is already present in his or her system. In this issue of the Journal, Murnane et al. (Am J Epidemiol. 2015;182(10):848-856) use data from the Partners PrEP Study (Kenya and Uganda, 2008-2011) to estimate the efficacy of PrEP under perfect adherence. We discuss Murnane et al.'s work and then examine the larger issues of generalizability or transportability of findings from a randomized trial to a new setting when adherence to an intervention determines its effectiveness. We discuss sufficient conditions for generalizability and use causal directed acyclic graphs to show how these assumptions might play out when trials are used to make inferences about the effect of PrEP in current and future real-world target populations.}, } @article {pmid26463931, year = {2016}, author = {McBride, DW and Tang, J and Zhang, JH}, title = {Development of an Infarct Volume Algorithm to Correct for Brain Swelling After Ischemic Stroke in Rats.}, journal = {Acta neurochirurgica. Supplement}, volume = {121}, number = {}, pages = {103-109}, doi = {10.1007/978-3-319-18497-5_18}, pmid = {26463931}, issn = {0065-1419}, support = {R01 NS084921/NS/NINDS NIH HHS/United States ; R01 NS043338/NS/NINDS NIH HHS/United States ; }, mesh = {*Algorithms ; Animals ; Brain/*pathology ; Brain Edema/*pathology ; Brain Infarction/*pathology ; Disease Models, Animal ; Hypoxia-Ischemia, Brain/*pathology ; Infarction, Middle Cerebral Artery/*pathology ; Male ; Rats ; Rats, Sprague-Dawley ; Stroke ; }, abstract = {The primary measure for experimental stroke studies, infarct volume, can be affected by brain swelling. The algorithm by Lin et al. was developed to correct for brain swelling, however, the correction is not adequate. This chapter presents a new infarct volume algorithm that more appropriately corrects for brain hemisphere volume changes (swelling and stunted growth). Fifty-one adult rats were sacrificed 24 h after middle cerebral artery occlusion (MCAO). Forty-four P10 rat pups were sacrificed 48 h after hypoxia-ischemia (HI). Infarct volumes for 2,3,5-triphenyl-2H-tetrazolium chloride (TTC) stained brains were calculated using our algorithm and that of Lin and colleagues. For MCAO animals, the algorithm of Lin et al. computed smaller infarct volumes than those of our algorithm. For HI animals, Lin et al.'s algorithm's infarct volumes were greater than those of our algorithm. For sham animals, Lin et al.'s algorithm's computed infarct volumes were significantly different from those of our algorithm. Our algorithm produces a more robust estimation of infarct volume than Lin et al.'s algorithm because the effects of ipsilesional hemisphere volume changes are minimized. Herein, our algorithm yields an infarct volume that better corrects for brain swelling and stunted brain growth compared with the algorithm of Lin et al.}, } @article {pmid26463418, year = {2015}, author = {Smith, GT and Davis, HA}, title = {Commentary: An exemplar of progress in understanding complex disorders - reflections on what we have learned about eating disorders (Culbert et al., 2015).}, journal = {Journal of child psychology and psychiatry, and allied disciplines}, volume = {56}, number = {11}, pages = {1165-1167}, pmid = {26463418}, issn = {1469-7610}, support = {R01 AA016166/AA/NIAAA NIH HHS/United States ; R01 AA 016166/AA/NIAAA NIH HHS/United States ; }, mesh = {*Feeding and Eating Disorders ; Humans ; }, abstract = {A number of recent advances in eating disorders research have helped clarify the nature of risk for the development of such disorders. Culbert et al. () provide an empirical and thoughtful review of these recent advances. The authors identified empirically established risk factors in each of several categories of risk for eating disorders: genetic influences, neurotransmitter activity, hormones, personality, and sociocultural influences. We highlight three implications of their review. First, the review can serve as an important asset to eating disorder researchers, both substantively, by providing a comprehensive account of empirically supported risk processes; and methodologically, by highlighting good standards of evidence for acceptance of a candidate risk factor. Second, eating disorder risk is increased by both transdiagnostic and eating disorder-specific factors; there is a need to understand how these types of factors transact with each other. Third and most important, we highlight the importance of Culbert et al.'s advocacy for the development of theoretical models, and empirical tests of those models that specify transactions among different types of risk factors, such as those based on genetic, neurobiological, personality, and social processes.}, } @article {pmid26460979, year = {2015}, author = {Ellis, MV and Creaner, M and Hutman, H and Timulak, L}, title = {A comparative study of clinical supervision in the Republic of Ireland and the United States.}, journal = {Journal of counseling psychology}, volume = {62}, number = {4}, pages = {621-631}, doi = {10.1037/cou0000110}, pmid = {26460979}, issn = {0022-0167}, mesh = {Adult ; Humans ; *Internationality ; Ireland/epidemiology ; Male ; Middle Aged ; Psychology/*education/*methods/standards ; Psychotherapy/*education/*methods/standards ; *Students, Health Occupations/psychology ; United States/epidemiology ; }, abstract = {We replicated Son, Ellis, and Yoo (2013) and extended Ellis et al.'s (2014) taxonomy of harmful and inadequate supervision by providing and testing cross-national comparative descriptive data about clinical supervision practices in the Republic of Ireland versus the United States. Participants were 149 Republic of Ireland and 151 U.S. mental health supervisees currently receiving clinical supervision. The results suggested that characteristics of supervision in the Republic of Ireland and United States evidenced both similarities and differences. The dissimilar credentialing systems appeared to account for the observed differences, suggesting that Ellis et al.'s (2014) criteria for inadequate supervision need to be modified to account for country-specific standards for supervision. Unexpectedly, no significant differences were observed between the Republic of Ireland and United States in the high occurrence of inadequate, harmful, or exceptional supervision. The results suggested that 79.2% (Republic of Ireland) and 69.5% (United States) of the supervisees were categorized as currently receiving inadequate supervision, and 40.3% (Republic of Ireland) and 25.2% (United States) of the supervisees as receiving harmful supervision. At some point in their careers, 92.4% (Republic of Ireland) and 86.4% (United States) of the supervisees received inadequate supervision--51.7% (Republic of Ireland) and 39.7% (United States) received harmful supervision. On the positive side, 51.0% (Republic of Ireland) and 55.0% (United States) of the supervisees reported receiving exceptional supervision from their current supervisors. Substantial discrepancies were observed between supervisees' perceptions versus more objective criteria of the inadequate or harmful supervision they received. Implications for cross-national supervision research and training are discussed.}, } @article {pmid26459671, year = {2016}, author = {Hiew, FL and Rajabally, YA}, title = {Sural sparing in Guillain-Barré syndrome subtypes: a reappraisal with historical and recent definitions.}, journal = {Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology}, volume = {127}, number = {2}, pages = {1683-1688}, doi = {10.1016/j.clinph.2015.09.131}, pmid = {26459671}, issn = {1872-8952}, mesh = {Adult ; Aged ; Electrodiagnosis/methods ; Female ; Guillain-Barre Syndrome/*diagnosis/*physiopathology ; Humans ; Male ; Middle Aged ; Neural Conduction/*physiology ; Retrospective Studies ; Sural Nerve/*physiology ; }, abstract = {OBJECTIVE: To ascertain the impact of definition and diagnostic criteria on sural sparing in Guillain-Barré syndrome (GBS).

METHODS: We retrospectively reviewed records of 78 consecutive patients with GBS from Birmingham, UK (2001-2012) studied within 21 days post-onset. Different criteria were initially used for subtype classification. Sural sparing was subsequently ascertained using historical/recent definitions.

RESULTS: With Hadden et al.'s criteria, "absent median present sural" and "absent median normal sural" patterns offered sensitivities of 21.7% and 15.2% respectively for AIDP, with specificities of 100% versus axonal GBS. Present sural with two abnormal upper limb responses had a sensitivity of 19.1% and 100% specificity. "Abnormal radial present sural" and "abnormal radial normal sural" patterns had sensitivities of 18.9% and 16.2% and specificity of 100%. With newly-proposed criteria (Rajabally et al., 2015), "absent median present sural" and "absent median normal sural" patterns offered sensitivities of 27.8% and 19.4% respectively, with specificity of 100%. Ulnar patterns were unhelpful with both criteria. Other patterns had suboptimal specificity.

CONCLUSION: Although of low sensitivity, sural sparing defined by absent median/present sural patterns, is specific of AIDP versus axonal GBS, irrespective of criteria.

SIGNIFICANCE: Sural sparing is definition and criteria-dependent in GBS but is specific of AIDP with historical definitions, regardless of criteria.}, } @article {pmid26450528, year = {2015}, author = {Sadat Hoseini, AS}, title = {Dr. Sadat Hosseini et al.'s Response to Comments.}, journal = {International journal of nursing knowledge}, volume = {26}, number = {4}, pages = {149}, doi = {10.1111/2047-3095.12116}, pmid = {26450528}, issn = {2047-3095}, mesh = {Nursing ; *Peer Review, Research ; }, } @article {pmid26447010, year = {2015}, author = {Spencer, L and Rollo, M and Hauck, Y and MacDonald-Wicks, L and Wood, L and Hutchesson, M and Giglia, R and Smith, R and Collins, C}, title = {The effect of weight management interventions that include a diet component on weight-related outcomes in pregnant and postpartum women: a systematic review protocol.}, journal = {JBI database of systematic reviews and implementation reports}, volume = {13}, number = {1}, pages = {88-98}, doi = {10.11124/jbisrir-2015-1812}, pmid = {26447010}, issn = {2202-4433}, mesh = {Adult ; Body Weight/physiology ; Diet Therapy/*methods ; Diet, Reducing/*methods ; Exercise/physiology ; Female ; Humans ; Incidence ; Life Style ; Obesity/epidemiology ; Postpartum Period/*physiology ; Pregnancy ; Pregnancy Complications/epidemiology/etiology ; Pregnancy Outcome/*epidemiology ; Randomized Controlled Trials as Topic ; Systematic Reviews as Topic ; }, abstract = {REVIEW QUESTION/OBJECTIVE: What are the effects of weight management interventions that include a diet component on weight-related outcomes in pregnant and postpartum women?The primary objective of this systematic review is to evaluate the effectiveness of weight management interventions which include a diet component and are aimed at limiting gestational weight gain and postpartum weight retention in women.The second objective of this systematic review is to investigate included intervention components with respect to effect on weight-related outcomes. This may include, but is not limited to: length of intervention, use of face-to-face counselling, group or individual consultations, use of other interventions components including exercise, use of goals and use of support tools like food diaries, coaching, including email or text message support.

BACKGROUND: Around half of all women of reproductive age are either overweight or obese, with women aged 25-34 years having a greater risk of substantial weight gain compared with men of all ages. Excessive gestational weight gain (GWG) and postpartum weight retention (PPWR) may play a significant role in long term obesity. Having one child doubles the five- and 10-year obesity incidence for women, with many women who gain excessive weight during pregnancy remaining obese permanently. Excessive GWG and/or PPWR can also significantly contribute to short- and long-term adverse health outcomes for mother, baby and future pregnancies.Maternal obesity increases the risk of pregnancy related complications such as pre-eclampsia, gestational diabetes mellitus, stillbirth and the rate of caesarean section. Childhood obesity is a further long term complication of maternal obesity for offspring, which may persist in to adulthood. Excess GWG is also a risk factor for PPWR both in the short and long-term. Nehring et al. conducted a meta-analysis with over 65,000 women showing that, compared to women who gained weight within recommendations during pregnancy, women with GWG above Institute of Medicine weight gain recommendations, retained an additional 3.1 kg and 4.7kg after three and greater than or equal to 15 years postpartum, respectively. The health risk associated with PPWR is highlighted in a study of 151,025 Swedish women followed between 1992 and 2001.The study identified the risk of adverse pregnancy outcomes for those who gained three or more units of Body Mass Index (kg/m2) between consecutive pregnancies (an average of two years) was much higher compared with women whose BMI changed from -1.0 and 0.9 units. Long-term chronic disease risk may also be affected by PPWR as weight retention at the end of the first year post-partum has been found to be a predictor of maternal overweight 15 years later.With around 14-20% of women retaining 5kg or more 12 months postpartum, the risk of developing conditions like diabetes, metabolic syndrome and cardiovascular disease may be increased. It becomes evident that interventions which aim to support attainment of healthy weight both in the antenatal and postpartum periods are key health priorities for women during this life stage.Lifestyle factors of overweight, having poor diet quality, and not undertaking enough moderate-to-vigorous physical activity are amongst the top five predictors of mortality in women. Additionally it is noted that, for many women, pregnancy and the postpartum period are associated with a reduction in physical activity. It is known that a combination of poor dietary choices, an increase in sedentary time and reduction in physical activity are all contributors to the development of overweight and obesity. With this in mind, current research has focused on lifestyle interventions to limit GWG and PPWR. Thangaratinam et al. reviewed 44 randomized controlled trials (7278 women) where interventions including diet, physical activity or both were evaluated for their influence on maternal weight during pregnancy. Results indicate that all were significantly effective in reducing GWG compared with the control group. More specifically, dietary interventions were the most effective in reducing weight gain, with a mean weight loss of -3.84kg compared with -0.72kg and -1.06kg for physical activity and the mixed (diet plus physical activity) approach, respectively. This finding is supported by Hill and colleagues' recent systematic review of theory based interventions to limit GWG. Included studies in this review reported an underpinning theory base and were classified as adopting a dietary, physical activity or mixed approach. Hill et al. concluded that studies which included a diet intervention were significantly more effective at limiting GWG.In 2011 Tanentsapf et al. reviewed the effect of dietary interventions alone for reducing GWG in normal weight, overweight and obese pregnant women. This review analysed 13 randomized controlled trials and quasi-randomized controlled trials with a dietary intervention to prevent excessive GWG in women. The review concluded that dietary interventions during pregnancy were effective in reducing GWG with an effect of -1.92kg (n=1434) compared with the control group.Tanentsapf et al. identified that trials differed in the conduct of the interventions with various diet and non-diet related components utilised. Dietary approaches were highly variable with some trials focusing only on calorie restriction and others included additional target macronutrient distribution for intake. Some trials further provided feedback based on maternal weight gain guidelines. Interventions also varied in delivery method with a variety of modes used, including face-to-face, individual or group consultations and/or written correspondence. The frequency of communication, despite the type or mix, also changed from trial to trial with additional methods via telephone, posted materials, feedback or food diaries utilised. The inclusion of physical activity in addition to diet intervention was also common. Whilst the recent review by Tanentsapf et al. identified that dietary interventions are effective in reducing GWG, the review did not investigate the impact that different intervention components, delivery methods or dietary counselling approaches had on gestational weight management. It remains unclear as to which intervention components optimize GWG in women.The impact of lifestyle interventions has also been investigated in the postpartum period. The recent systematic review from van der Pligt et al. reported seven of 11 studies reviewed were successful in limiting PPWR. As with studies aimed at limiting GWG, interventions included in van der Pligt et al.'s review differed greatly in their conduct. Six of these seven studies included both dietary and physical activity components for the intervention, with the final successful study including a diet only intervention. Five of the successful studies recruited overweight or obese women only. Intervention time varied considerably in successful studies with some running for as little at ten days, and others up to six months.Bertz et al. demonstrated that their 12-week behavior modification intervention which targeted diet alone or diet and exercise, including two individual sessions with a dietitian and physical therapist, provision of scales for weight self-monitoring and bi-weekly text messages was successful in achieving significant weight loss following the intervention, and sustained at one year. The diet intervention and the diet and exercise intervention yielded significant weight loss compared to the control. Following 12 weeks a reduction of -8.3 +/- 4.2kg for diet intervention and -6.9 +/- 3.0kg for diet and exercise was observed. Additionally after one year, the diet intervention showed -10.2 +/- 5.7kg reduction and -7.3 +/- 6.3kg for the diet and exercise intervention (p<0.001). Colleran et al. also found significant weight change results by implementing a 16-week intervention which consisted of weekly individual sessions with a dietitian regarding calorie restriction, two additional home visits regarding exercise, weekly food diary completion and email support. The intervention group had greater weight loss compared to the control group (-5.8kg +/- 3.5kg vs -1.6kg +/- 5.4kg). It can be seen that various methods have been utilized in investigating the impact of diet and physical activity interventions on PPWR. The review by van der Pligt et al. highlights the impact successful lifestyle interventions can have on postpartum weight change. However, this review did not investigate the different intervention strategies utilized. It remains unclear as to the optimal setting, delivery method, diet strategy, contact frequency or intervention length to limit PPWR.Previous systematic reviews for both GWG and PPWR have focused on the effectiveness of lifestyle interventions as a whole for weight management in pregnant and postpartum women. And despite Tanentsapf et al.'s focus on dietary interventions for GWG, much is still unknown about the effectiveness of differing diet interventions over the antenatal and postpartum period. Specifically, the impact of differing diet intervention strategies on maternal weight gain is not known. Firstly, this systematic review will focus on whether weight management interventions which include a dietary component are effective in pregnant and postpartum women. In addition to this, this review will investigate the different intervention strategies utilized and their effectiveness in maternal weight management. A search of systematic review protocol databases has shown that there is no current review underway for this topic.}, } @article {pmid26440485, year = {2015}, author = {Lee, YC and Wu, HH and Hsieh, WL and Weng, SJ and Hsieh, LP and Huang, CH}, title = {Applying importance-performance analysis to patient safety culture.}, journal = {International journal of health care quality assurance}, volume = {28}, number = {8}, pages = {826-840}, doi = {10.1108/IJHCQA-03-2015-0039}, pmid = {26440485}, issn = {1758-6542}, mesh = {Adult ; *Attitude of Health Personnel ; Environment ; Female ; Group Processes ; Humans ; Interpersonal Relations ; Job Satisfaction ; Male ; Middle Aged ; *Organizational Culture ; *Patient Safety ; Safety Management/*organization & administration ; Stress, Psychological/psychology ; Taiwan ; }, abstract = {PURPOSE: The Sexton et al.'s (2006) safety attitudes questionnaire (SAQ) has been widely used to assess staff's attitudes towards patient safety in healthcare organizations. However, to date there have been few studies that discuss the perceptions of patient safety both from hospital staff and upper management. The purpose of this paper is to improve and to develop better strategies regarding patient safety in healthcare organizations.

DESIGN/METHODOLOGY/APPROACH: The Chinese version of SAQ based on the Taiwan Joint Commission on Hospital Accreditation is used to evaluate the perceptions of hospital staff. The current study then lies in applying importance-performance analysis technique to identify the major strengths and weaknesses of the safety culture.

FINDINGS: The results show that teamwork climate, safety climate, job satisfaction, stress recognition and working conditions are major strengths and should be maintained in order to provide a better patient safety culture. On the contrary, perceptions of management and hospital handoffs and transitions are important weaknesses and should be improved immediately. Research limitations/implications - The research is restricted in generalizability. The assessment of hospital staff in patient safety culture is physicians and registered nurses. It would be interesting to further evaluate other staff's (e.g. technicians, pharmacists and others) opinions regarding patient safety culture in the hospital.

ORIGINALITY/VALUE: Few studies have clearly evaluated the perceptions of healthcare organization management regarding patient safety culture. Healthcare managers enable to take more effective actions to improve the level of patient safety by investigating key characteristics (either strengths or weaknesses) that healthcare organizations should focus on.}, } @article {pmid26433945, year = {2016}, author = {Patton, R and Boniface, S}, title = {Prevalence of Hazardous Drinking Among UK 18-35 Year Olds; the Impact of a Revision to the AUDIT Cut Score.}, journal = {Alcohol and alcoholism (Oxford, Oxfordshire)}, volume = {51}, number = {3}, pages = {281-282}, doi = {10.1093/alcalc/agv115}, pmid = {26433945}, issn = {1464-3502}, mesh = {Adolescent ; Adult ; Alcohol Drinking/*epidemiology ; *Dangerous Behavior ; Female ; Humans ; Male ; Prevalence ; United Kingdom/epidemiology ; Young Adult ; }, abstract = {AIM: Most published research utilizes an AUDIT score of >8 as the threshold for hazardous drinking. Recent research suggests that this limit should be amended for younger drinkers (aged 18-35 years). This study aimed to explore the effect of a revision to AUDIT cut scores.

METHOD: Applying Foxcroft et al.'s [(2015) Accuracy of Alcohol Use Disorders Identification Test for detecting problem drinking in 18-35 year-olds in England: method comparison study. Alcohol Alcohol 50, 244-50] suggested cut off scores of nine for males and four for females to the most recent Adult Psychiatric Morbidity Survey (2007) data.

RESULTS: This more than doubles the prevalence of female hazardous drinkers, and significantly increases the overall rate for that age group when compared with the standard threshold of >8.

CONCLUSION: The prevalence of hazardous drinking among females ages 18-30 may be significantly higher than current estimates.}, } @article {pmid26432077, year = {2015}, author = {Casasanto, D and Brookshire, G and Ivry, R}, title = {Meaning is Not a Reflex: Context Dependence of Spatial Congruity Effects.}, journal = {Cognitive science}, volume = {39}, number = {8}, pages = {1979-1986}, doi = {10.1111/cogs.12294}, pmid = {26432077}, issn = {1551-6709}, mesh = {*Emotions ; Humans ; Reflex ; *Semantics ; }, abstract = {In two experiments, Brookshire, Ivry, and Casasanto (2010) showed that words with positive and negative emotional valence can activate spatial representations with a high degree of automaticity, but also that this activation is highly context dependent. Lebois, Wilson-Mendenhall, and Barsalou (2015) reported that they "aimed to replicate" our study but found only null results in the "Brookshire et al. replication" conditions. Here we express concerns about three aspects of this paper. First, the study was not an attempt to replicate ours; it was a different study that adapted our method. Second, Lebois et al. did not accurately represent our theoretical position. Third, Lebois et al.'s main conclusion, that spatial congruity effects depend on the task context, was not supported by their data. Despite these concerns, we agree with Lebois et al.'s overall message that spatial aspects of words' meanings are activated differently in different contexts. This was a main conclusion of our study as well.}, } @article {pmid26423324, year = {2015}, author = {Lebois, LA and Wilson-Mendenhall, CD and Barsalou, LW}, title = {Putting Everything in Context.}, journal = {Cognitive science}, volume = {39}, number = {8}, pages = {1987-1995}, doi = {10.1111/cogs.12295}, pmid = {26423324}, issn = {1551-6709}, abstract = {In response to Casasanto, Brookshire, and Ivry (2015), we address four points: First, we engaged in conceptual replications of Brookshire, Casasanto, and Ivry (2010), not direct replications. Second, we did not question the validity of Brookshire et al.'s (2010) results, nor the similar findings of other researchers, but instead explained divergent findings within an integrated theoretical framework. Third, challenges to the construct of automaticity, including ours, were widespread, long before Brookshire et al.'s (2010) article. Fourth, the planned comparisons that we reported tested our theoretical claims and offered strong evidence for them.}, } @article {pmid26401928, year = {2015}, author = {Fins, JJ}, title = {The Reagan Diaries Reconsidered.}, journal = {Journal of Alzheimer's disease : JAD}, volume = {48}, number = {1}, pages = {59-61}, doi = {10.3233/JAD-150354}, pmid = {26401928}, issn = {1875-8908}, mesh = {*Alzheimer Disease ; *Famous Persons ; Humans ; *Politics ; United States ; }, abstract = {Using critical methods drawn from clinical ethics and the humanities, the author considers the posthumously published The Reagan Diaries and suggests that they show evidence of an incipient dementia. In the wake of Berisha et al.'s analysis of presidential press conferences during the Reagan presidency, published in the Journal of Alzheimer's Disease, that were suggestive of cognitive impairment, this reading of the president's diaries merit additional scrutiny. Diary entries from Reagan's second term differ from the first years of his presidency. They demonstrate less text, more laconic analysis, word finding difficulties, evidence of spatial confusion and suggestions of disinhibition, all possibly early signs of cognitive impoverishment during the same period when the transcripts of his second term press conferences showed evidence suggestive of incipient Alzheimer's Disease. While a definitive analysis of the president's diaries can not be performed on the abridged published text, edited by the historian Douglas Brinkley, these findings are suggestive and warrant additional scrutiny. By melding quantitative approaches analyzing language use from Reagan's presidential press conferences with methods from clinical ethics and literary criticism, future scholars can gain a fuller understanding of the president's health while he was in office.}, } @article {pmid26399937, year = {2015}, author = {Chaudhry, SA and Mahmood, K and Naqvi, H and Khan, MK}, title = {An Improved and Secure Biometric Authentication Scheme for Telecare Medicine Information Systems Based on Elliptic Curve Cryptography.}, journal = {Journal of medical systems}, volume = {39}, number = {11}, pages = {175}, pmid = {26399937}, issn = {1573-689X}, mesh = {Algorithms ; Biometric Identification/*instrumentation ; Computer Security/*instrumentation ; Confidentiality ; Humans ; Telemedicine/*instrumentation ; Wireless Technology ; }, abstract = {Telecare medicine information system (TMIS) offers the patients convenient and expedite healthcare services remotely anywhere. Patient security and privacy has emerged as key issues during remote access because of underlying open architecture. An authentication scheme can verify patient's as well as TMIS server's legitimacy during remote healthcare services. To achieve security and privacy a number of authentication schemes have been proposed. Very recently Lu et al. (J. Med. Syst. 39(3):1-8, 2015) proposed a biometric based three factor authentication scheme for TMIS to confiscate the vulnerabilities of Arshad et al.'s (J. Med. Syst. 38(12):136, 2014) scheme. Further, they emphasized the robustness of their scheme against several attacks. However, in this paper we establish that Lu et al.'s scheme is vulnerable to numerous attacks including (1) Patient anonymity violation attack, (2) Patient impersonation attack, and (3) TMIS server impersonation attack. Furthermore, their scheme does not provide patient untraceability. We then, propose an improvement of Lu et al.'s scheme. We have analyzed the security of improved scheme using popular automated tool ProVerif. The proposed scheme while retaining the plusses of Lu et al.'s scheme is also robust against known attacks.}, } @article {pmid26399282, year = {2015}, author = {Herrera, GA and Turbat-Herrera, EA}, title = {Reply to Sim et al.'s Letter to the Editor: Electron Microscopy Is Crucial in Establishing or Confirming a Diagnosis of Cryoglobulinemic Nephropathy.}, journal = {Ultrastructural pathology}, volume = {39}, number = {5}, pages = {357-358}, doi = {10.3109/01913123.2015.1081311}, pmid = {26399282}, issn = {1521-0758}, mesh = {Cryoglobulinemia/*pathology ; Female ; Humans ; Kidney/*ultrastructure ; Kidney Diseases/*pathology ; Male ; *Microscopy, Electron, Transmission ; }, } @article {pmid26397162, year = {2015}, author = {Hickey, JL and James, JL and Henderson, CA and Price, KA and Mot, AI and Buncic, G and Crouch, PJ and White, JM and White, AR and Smith, TA and Donnelly, PS}, title = {Intracellular distribution of fluorescent copper and zinc bis(thiosemicarbazonato) complexes measured with fluorescence lifetime spectroscopy.}, journal = {Inorganic chemistry}, volume = {54}, number = {19}, pages = {9556-9567}, doi = {10.1021/acs.inorgchem.5b01599}, pmid = {26397162}, issn = {1520-510X}, mesh = {Cell Line, Tumor ; Coordination Complexes/chemical synthesis/chemistry/*pharmacokinetics ; Copper/*chemistry ; *Fluorescence ; Humans ; Models, Molecular ; Molecular Structure ; Spectrometry, Fluorescence ; Thiosemicarbazones/*chemistry ; Time Factors ; Tissue Distribution ; Zinc/*chemistry ; }, abstract = {The intracellular distribution of fluorescently labeled copper and zinc bis(thiosemicarbazonato) complexes was investigated in M17 neuroblastoma cells and primary cortical neurons with a view to providing insights into the neuroprotective activity of a copper bis(thiosemicarbazonato) complex known as Cu(II)(atsm). Time-resolved fluorescence measurements allowed the identification of the Cu(II) and Zn(II) complexes as well as the free ligand inside the cells by virtue of the distinct fluorescence lifetime of each species. Confocal fluorescent microscopy of cells treated with the fluorescent copper(II)bis(thiosemicarbazonato) complex revealed significant fluorescence associated with cytoplasmic puncta that were identified to be lysosomes in primary cortical neurons and both lipid droplets and lysosomes in M17 neuroblastoma cells. Fluorescence lifetime imaging microscopy confirmed that the fluorescence signal emanating from the lipid droplets could be attributed to the copper(II) complex but also that some degree of loss of the metal ion led to diffuse cytosolic fluorescence that could be attributed to the metal-free ligand. The accumulation of the copper(II) complex in lipid droplets could be relevant to the neuroprotective activity of Cu(II)(atsm) in models of amyotrophic lateral sclerosis and Parkinson's disease.}, } @article {pmid26391034, year = {2015}, author = {Hickok, G}, title = {The interface theory of perception: the future of the science of the mind?.}, journal = {Psychonomic bulletin & review}, volume = {22}, number = {6}, pages = {1477-1479}, doi = {10.3758/s13423-015-0930-4}, pmid = {26391034}, issn = {1531-5320}, mesh = {*Biological Evolution ; Humans ; *Perception ; *Psychological Theory ; }, abstract = {Perception is typically conceptualized as a neurocognitive system that evolved to reveal the truth about objects and events in the world. Hoffman et al.'s Interface Theory of Perception questions this assumption. If true, the implications for the science of the mind are profound.}, } @article {pmid26384989, year = {2015}, author = {Pizlo, Z}, title = {Philosophizing cannot substitute for experimentation: comment on Hoffman, Singh & Prakash (2014).}, journal = {Psychonomic bulletin & review}, volume = {22}, number = {6}, pages = {1546-1547}, pmid = {26384989}, issn = {1531-5320}, support = {R01 EY024666/EY/NEI NIH HHS/United States ; 1R01EY024666-01/EY/NEI NIH HHS/United States ; }, mesh = {*Biological Evolution ; Humans ; *Perception ; *Psychological Theory ; }, abstract = {The perception of a 3D shape must be excluded from Hoffman et al.'s "interface theory" primarily because shape is characterized by its symmetries. When these symmetries are used as a priori constraints, 3D shapes are always recovered from 2D retinal images veridically. These facts make it clear that 3D shape perception is completely different from, as well as more important than, all other perceptions because the veridicality of our perception of 3D shapes (and 3D scenes) accounts for our successful adaptation to the natural environment.}, } @article {pmid26383040, year = {2015}, author = {Cunha, LF and Kowada, LA and Hausen, Rde A and de Figueiredo, CM}, title = {A faster 1.375-approximation algorithm for sorting by transpositions.}, journal = {Journal of computational biology : a journal of computational molecular cell biology}, volume = {22}, number = {11}, pages = {1044-1056}, doi = {10.1089/cmb.2014.0298}, pmid = {26383040}, issn = {1557-8666}, mesh = {Algorithms ; Computational Biology ; Gene Rearrangement ; Models, Genetic ; *Sequence Analysis, DNA ; }, abstract = {Sorting by Transpositions is an NP-hard problem for which several polynomial-time approximation algorithms have been developed. Hartman and Shamir (2006) developed a 1.5-approximation [Formula: see text] algorithm, whose running time was improved to O(nlogn) by Feng and Zhu (2007) with a data structure they defined, the permutation tree. Elias and Hartman (2006) developed a 1.375-approximation O(n(2)) algorithm, and Firoz et al. (2011) claimed an improvement to the running time, from O(n(2)) to O(nlogn), by using the permutation tree. We provide counter-examples to the correctness of Firoz et al.'s strategy, showing that it is not possible to reach a component by sufficient extensions using the method proposed by them. In addition, we propose a 1.375-approximation algorithm, modifying Elias and Hartman's approach with the use of permutation trees and achieving O(nlogn) time.}, } @article {pmid26382089, year = {2016}, author = {Mackintosh, N and Sandall, J}, title = {The social practice of rescue: the safety implications of acute illness trajectories and patient categorisation in medical and maternity settings.}, journal = {Sociology of health & illness}, volume = {38}, number = {2}, pages = {252-269}, pmid = {26382089}, issn = {1467-9566}, support = {10/1008/35/DH_/Department of Health/United Kingdom ; NIHR-PSSQRF-003/DH_/Department of Health/United Kingdom ; }, mesh = {Anthropology, Cultural ; Clinical Competence ; Efficiency, Organizational ; Emergency Treatment/*standards ; *Failure to Rescue, Health Care ; Female ; Hospital Departments/organization & administration ; Hospitals, Urban/organization & administration ; Humans ; Obstetrics and Gynecology Department, Hospital/*organization & administration/standards ; *Patient Safety ; Pregnancy ; Quality of Health Care/*organization & administration/standards ; Socioeconomic Factors ; Sociology, Medical ; Time Factors ; United Kingdom ; }, abstract = {The normative position in acute hospital care when a patient is seriously ill is to resuscitate and rescue. However, a number of UK and international reports have highlighted problems with the lack of timely recognition, treatment and referral of patients whose condition is deteriorating while being cared for on hospital wards. This article explores the social practice of rescue, and the structural and cultural influences that guide the categorisation and ordering of acutely ill patients in different hospital settings. We draw on Strauss et al.'s notion of the patient trajectory and link this with the impact of categorisation practices, thus extending insights beyond those gained from emergency department triage to care management processes further downstream on the hospital ward. Using ethnographic data collected from medical wards and maternity care settings in two UK inner city hospitals, we explore how differences in population, cultural norms, categorisation work and trajectories of clinical deterioration interlink and influence patient safety. An analysis of the variation in findings between care settings and patient groups enables us to consider socio-political influences and the specifics of how staff manage trade-offs linked to the enactment of core values such as safety and equity in practice.}, } @article {pmid26378396, year = {2015}, author = {Klass, K and Cords, M}, title = {Agonism and dominance in female blue monkeys.}, journal = {American journal of primatology}, volume = {77}, number = {12}, pages = {1299-1315}, doi = {10.1002/ajp.22481}, pmid = {26378396}, issn = {1098-2345}, mesh = {Aggression ; *Agonistic Behavior ; Animals ; Behavior, Animal ; Cercopithecus/*physiology ; Female ; Kenya ; Phylogeny ; Population Density ; *Social Behavior ; *Social Dominance ; }, abstract = {Agonistic behavior features prominently in hypotheses that explain how social variation relates to ecological factors and phylogenetic constraints. Dominance systems vary along axes of despotism, tolerance, and nepotism, and comparative studies examine cross-species patterns in these classifications. To contribute to such studies, we present a comprehensive picture of agonistic behavior and dominance relationships in wild female blue monkeys (Cercopithecus mitis), an arboreal guenon, with data from 9 groups spanning 18 years. We assessed where blue monkeys fall along despotic, tolerant, and nepotistic spectra, how their dominance system compares to other primates, primarily cercopithecines, and whether their agonistic behavior matches socioecological model predictions. Blue monkeys showed low rates of mainly low-intensity agonism and little counter-aggression. Rates increased with rank and group size. Dominance asymmetry varied at different organizational levels, being more pronounced at the level of interactions than dyad or group. Hierarchies were quite stable, had moderate-to-high linearity and directional consistency and moderate steepness. There was clear maternal rank inheritance, but inconsistent adherence to Kawamura's rules. There was little between-group variation, although hierarchy metrics showed considerable variation across group-years. Overall, blue monkeys have moderately despotic, moderately tolerant, and nepotistic dominance hierarchies. They resemble other cercopithecines in having significantly linear and steep hierarchies with a generally stable, matriline-based structure, suggesting a phylogenetic basis to this aspect of their social system. Blue monkeys most closely match Sterck et al.'s [1997] Resident-Nepotistic-Tolerant dominance category, although they do not fully conform to predictions of any one socioecological model. Our results suggest that socioecological models might better predict variation within than across clades, thereby incorporating both ecological variables and phylogenetic constraints. Our findings also highlight the need for clearer definitions of socioecologically relevant dominance categories, which would ideally derive from quantitative measures of dominance behavior. Intraspecific and methodological variation may, however, be a challenge.}, } @article {pmid26377995, year = {2015}, author = {Dimitrova-Karamfilova, A and Tzveova, R and Chilingirova, N and Goranova, T and Nachev, G and Mitev, V and Kaneva, R}, title = {Acenocoumarol Pharmacogenetic Dosing Algorithms and Their Application in Two Bulgarian Patients with Low Anticoagulant Requirements.}, journal = {Biochemical genetics}, volume = {53}, number = {11-12}, pages = {334-350}, doi = {10.1007/s10528-015-9695-8}, pmid = {26377995}, issn = {1573-4927}, mesh = {Acenocoumarol/*therapeutic use ; Algorithms ; Anticoagulants/*therapeutic use ; Aortic Valve/*surgery ; Bulgaria ; Coumarins/therapeutic use ; Dose-Response Relationship, Drug ; Female ; Genotype ; Humans ; Male ; Middle Aged ; Mitral Valve/*surgery ; Pharmacogenetics/methods ; Polymorphism, Single Nucleotide ; Thromboembolism/*drug therapy ; }, abstract = {BACKGROUND: The anticoagulant therapy with acenocoumarol is generally associated with a high risk of bleeding and thromboembolic events.

PURPOSE: We applied eight already existing acenocoumarol dosing algorithms to Bulgarian patients with low acenocoumarol dose requirements and investigated which of these algorithms would predict most precisely the dose anticoagulant.

MATERIALS AND METHODS: Two patients with Bulgarian origin were referred to the outpatient clinical laboratory of "St. Ekaterina" University Hospital for Cardiovascular Surgery and Cardiology, Sofia, Bulgaria. After obtaining written informed consent, both patients were genotyped for polymorphisms in genes for Cytochrome P450 2C9 (CYP2C9), Vitamin K epoxide reductase (VKORC1), Apolipoprotein E (APOE), and Cytochrome P450 4F2 (CYP4F2).

RESULTS: All applied acenocoumarol dosing algorithms predicted relatively similar doses of coumarin anticoagulant in both patients. However, van Schie et al.'s algorithm allowed more accurate calculation of the optimal dose in our patients with extremely low acenocoumarol requirements. Genotyping of selected polymorphic variants in CYP2C9 and VKORC1 showed that both patients were compound heterozygotes for CYP2C9 (CYP2C9*2/*3) and homozygotes for both variants in VKORC1 (VKORC1 1173 T/T, and VKORC1-1639 A/A). This combination of genotypes suggested high sensitivity to acenocoumarol leading to the low anticoagulant dose requirements (0.25 and 1 mg/day, respectively) needed to reach the target International Normalized Ratio of 2.5-3.5.

CONCLUSIONS: The genotyping of polymorphic variants in VKORC1 and CYP2C9, together with clinical and demographic parameters, can serve for more precise definition of the individual starting and maintenance doses of coumarin derivatives in each patient.}, } @article {pmid26374331, year = {2016}, author = {Malejka, S and Bröder, A}, title = {No source memory for unrecognized items when implicit feedback is avoided.}, journal = {Memory & cognition}, volume = {44}, number = {1}, pages = {63-72}, pmid = {26374331}, issn = {1532-5946}, mesh = {Adolescent ; Adult ; Feedback, Psychological/*physiology ; Female ; Humans ; Male ; Mental Recall/*physiology ; Middle Aged ; Recognition, Psychology/*physiology ; Signal Detection, Psychological/*physiology ; Young Adult ; }, abstract = {In a recent empirical study, Starns, Hicks, Brown, and Martin (Memory & Cognition, 36, 1-8 2008) collected source judgments for old items that participants had claimed to be new and found residual source discriminability depending on the old-new response bias. The authors interpreted their finding as evidence in favor of the bivariate signal-detection model, but against the two-high-threshold model of item/source memory. According to the latter, NEW responses only follow from the state of old-new uncertainty for which no source discrimination is possible, and the probability of entering this state is independent of the old-new response bias. However, when missed old items were presented for source discrimination, the participants could infer that the items had been previously studied. To test whether this implicit feedback led to second retrieval attempts and thus to source memory for presumably unrecognized items, we replicated Starns et al.'s (Memory & Cognition, 36, 1-8 2008) finding and compared their procedure to a procedure without such feedback. Our results challenge the conclusion to abandon discrete processing in source memory; source memory for unrecognized items is probably an artifact of the procedure, by which implicit feedback prompts participants to reconsider their recognition judgment when asked to rate the source of old items in the absence of item memory.}, } @article {pmid26362958, year = {2015}, author = {Şahin, H and Toman, H and Kiraz, HA and Şimşek, T and Erbaş, M and Özkul, F and Arık, MK and Hancı, V}, title = {Effects of sugammadex on the prevention of postoperative peritoneal adhesions.}, journal = {The Kaohsiung journal of medical sciences}, volume = {31}, number = {9}, pages = {463-467}, pmid = {26362958}, issn = {2410-8650}, mesh = {Animals ; Female ; Peritoneal Diseases/*drug therapy/etiology/*prevention & control ; Postoperative Complications/*drug therapy/etiology/*prevention & control ; Rats, Wistar ; Sugammadex ; Tissue Adhesions/*drug therapy/etiology/*prevention & control ; gamma-Cyclodextrins/*therapeutic use ; }, abstract = {Many materials and techniques have been used to prevent and repair intra-abdominal adhesions, but an effective solution has not been found. The aim of this study is to research the effect of sugammadex on intra-abdominal adhesions in an experimentally induced intra-abdominal adhesion model. Twenty-four female Wistar albino rats were included in the study. The experimental animals were randomly divided into three groups: the sugammadex group (Group SX, n = 8), the control group (Group C, n = 8), and the sham group (Group S, n = 8). After starvation for 1 night, the rats were injected with a 50 mg/kg intramuscular dose of ketamine and a 5 mg/kg intramuscular dose of xylazine for anesthesia. The rats in the SX group were given 3 mL sugammadex into the peritoneal cavity, while rats in the control group were given 3 mL 0.9% sodium chloride. In the sham group, the peritoneal cavity was opened, but no chemicals were administered. All rats were sacrificed on the 10(th) postoperative day. The adhesions were staged as 0, 1, 2, and 3 according to Evans et al.'s model. Our evaluation of macroscopic adhesion intensity found statistically significant differences between the groups. The sugammadex group was observed to have fewer adhesions in a statistically significant manner compared with the control group (p < 0.05). In our experimental intra-abdominal adhesion model in rats, we observed that sugammadex prevented postoperative intra-abdominal adhesions.}, } @article {pmid26360667, year = {2017}, author = {Takara, R and Beecher, ME and Okiishi, JC and Shimokawa, K and Lambert, MJ and Griner, D}, title = {Translation of the Outcome Questionnaire-45 (OQ) into Japanese: A cultural adaptation.}, journal = {Psychotherapy research : journal of the Society for Psychotherapy Research}, volume = {27}, number = {2}, pages = {154-166}, doi = {10.1080/10503307.2015.1080876}, pmid = {26360667}, issn = {1468-4381}, mesh = {Adult ; Aged ; Female ; Humans ; Japan ; Male ; Middle Aged ; Outcome Assessment, Health Care/*methods ; Psychometrics/instrumentation/*methods ; *Psychotherapy ; Surveys and Questionnaires/*standards ; Translations ; Young Adult ; }, abstract = {OBJECTIVE: While there are several Japanese, qualitative, case studies examining psychotherapy outcome, there is a growing need for quantitative psychotherapy outcome research in Japan. This study adapted the Outcome Questionnaire-45 (OQ), one of the most common quantitative measures of clinical outcome, for use in Japan.

METHOD: With the help of 6 translators and 116 native Japanese pilot respondents, the original OQ was translated into Japanese following Beaton et al.'s methodology and includes forward translation, synthesis, back translation, and expert committee meetings.

RESULTS: The study produced four pre-final versions, two pretest version, and one pilot version of the Japanese OQ. With permission from the original questionnaire developers, a few items were modified to achieve cultural equivalence. The rigorous translation and adaptation processes, evaluated through the Translation Validity Index and Content Validity Index provided semantic, content, and conceptual equivalence between the English and Japanese versions.

CONCLUSIONS: The current study partially validated the translation equivalence and cultural adaptation of the Japanese OQ. Study limitations and suggestions for further development are discussed.}, } @article {pmid26359446, year = {2015}, author = {Rosberger, Z and Perez, S and Bloom, J and Shapiro, GK and Fielding, R}, title = {The missing piece: cancer prevention within psycho-oncology - a commentary.}, journal = {Psycho-oncology}, volume = {24}, number = {10}, pages = {1330-1337}, doi = {10.1002/pon.3916}, pmid = {26359446}, issn = {1099-1611}, abstract = {In this commentary, we review the place of prevention within the field of Psycho-Oncology. The thrust of Psycho-Oncology's clinical and research efforts have historically focused on behavioral and social factors implicated in the cancer patients' experience from detection and diagnosis, to treatment, survivorship and end of life along the cancer trajectory. This conceptualization has raised the standards for research, leading to a better understanding of the patient experience and the delivery of highly effective interventions to improve quality of life. Emerging data on the role of potential prevention behaviors (e.g., diet and exercise, smoking cessation, screening, etc.) suggests that Psycho-Oncology has a significant role to play in understanding and intervening on a population level to reduce cancer incidence. We present and describe an expanded model of research in Psycho-Oncology which incorporates psychosocial variables in prevention research to complement Holland et al.'s (1998, 2010) original model. The implications of this model are discussed in relation to research, clinical work and training within the discipline of Psycho-Oncology. Copyright © 2015 John Wiley & Sons, Ltd.}, } @article {pmid26349612, year = {2017}, author = {Ho, IK and Dinh, KT and Smith, SA}, title = {Intimate partner violence and physical health outcomes among Southeast Asian American women.}, journal = {Journal of health psychology}, volume = {22}, number = {4}, pages = {515-525}, doi = {10.1177/1359105315603695}, pmid = {26349612}, issn = {1461-7277}, mesh = {Adult ; Asia, Southeastern/ethnology ; *Asian/psychology ; *Cultural Characteristics ; Disease/ethnology/*psychology ; Female ; *Health Status ; Humans ; Intimate Partner Violence/*ethnology/psychology ; Models, Biological ; Models, Psychological ; Prevalence ; Psychological Trauma/*complications/physiopathology/psychology ; *Social Environment ; }, abstract = {Although intimate partner violence is prevalent among Southeast Asian American women, little is known about the associations between the experience of intimate partner violence and negative health outcomes in this population. Resnick et al. proposed a model explaining the development of health problems following violent assault. This article assesses the applicability of Resnick et al.'s model to Southeast Asian American women who have experienced intimate partner violence by reviewing cultural, historical, and social factors in this population. Our review indicates that the applicability of Resnick et al.'s model to Southeast Asian American women is mixed, with some components of the model fitting well with this population and others requiring a more nuanced and complex perspective. Future studies should take into consideration cultural, historical, and social factors.}, } @article {pmid26348203, year = {2015}, author = {Adelman, JS and Estes, Z}, title = {Why to treat subjects as fixed effects.}, journal = {Journal of experimental psychology. Learning, memory, and cognition}, volume = {41}, number = {5}, pages = {1602-1605}, doi = {10.1037/xlm0000098}, pmid = {26348203}, issn = {1939-1285}, mesh = {Cognition ; Computer Simulation ; Humans ; Individuality ; *Models, Statistical ; Reaction Time/*physiology ; Reading ; }, abstract = {Adelman, Marquis, Sabatos-DeVito, and Estes (2013) collected word naming latencies from 4 participants who read 2,820 words 50 times each. Their recommendation and practice was that R[2] targets set for models should take into account subject idiosyncrasies as replicable patterns, equivalent to a subjects-as-fixed-effects assumption. In light of an interaction involving subjects, they broke down the interaction into individual subject data. Courrieu and Rey's (2015) commentary argues that (a) single-subject data need not be more reliable than subject-average data, and (b) anyway, treating groups of subjects as random samples leads to valid conclusions about general mechanisms of reading. Point (a) was not part of Adelman et al.'s claim. In this reply, we examine the consequences of using the fixed-effect assumption. It (a) produces the correct target to check if by-items regression models contain all necessary variables, (b) more accurately constrains cognitive models, (c) more accurately reveals general mechanisms, and (d) can offer more powerful tests of effects. Even when individual differences are not the primary focus of a study, the fixed-effect analysis is often preferable to the random-effects analysis.}, } @article {pmid26343474, year = {2015}, author = {Terrien, S and Stefaniak, N and Morvan, Y and Besche-Richard, C}, title = {Factor structure of the French version of the Hypomanic Personality Scale (HPS) in non-clinical young adults.}, journal = {Comprehensive psychiatry}, volume = {62}, number = {}, pages = {105-113}, doi = {10.1016/j.comppsych.2015.07.001}, pmid = {26343474}, issn = {1532-8384}, mesh = {Adult ; Bipolar Disorder/etiology/psychology ; Factor Analysis, Statistical ; Female ; Humans ; Male ; Personality Disorders/complications/*psychology ; Personality Inventory/*statistics & numerical data ; Psychiatric Status Rating Scales/*statistics & numerical data ; Psychometrics ; Reproducibility of Results ; Self Report ; *Translations ; Young Adult ; }, abstract = {BACKGROUND: Hypomanic Personality Scale (HPS) is a self-report questionnaire designed to identify vulnerable individuals at high risk of bipolar disorders in non-clinical samples. Our aim was to identify the factorial structure of HPS in a French non-clinical sample and to compare this with different factor solutions described in the literature. We carried out a survey in a French population using a French version of HPS.

METHODS: A total of 698 participants were included in the study. They completed the HPS, the Schizotypal Personality Questionnaire-Brief (SPQ-B), the Positive And Negative Affect Schedule (PANAS), and the Beck Depression Inventory (BDI-II). We tested the 1, 3 and 4-factor solutions and used a Confirmatory Factor Analysis to compare these with the factor solutions suggested by Rawling et al. and Schalet et al.

RESULTS: Goodness-of-fit indices showed that Schalet et al.'s solution "fits" our data better than Rawling et al.'s factorial solutions. HPS scores correlated with the PANAS Positive score and the SPQ-B total score. We confirmed the 3-factor structure of the HPS in a large non-clinical population of young adults and found consistent correlations with BDI, affectivity and schizotypal traits.}, } @article {pmid26342492, year = {2015}, author = {Amin, R and Islam, SK and Biswas, GP and Khan, MK and Li, X}, title = {Cryptanalysis and Enhancement of Anonymity Preserving Remote User Mutual Authentication and Session Key Agreement Scheme for E-Health Care Systems.}, journal = {Journal of medical systems}, volume = {39}, number = {11}, pages = {140}, pmid = {26342492}, issn = {1573-689X}, mesh = {Algorithms ; Biometric Identification/*instrumentation ; Computer Security/*instrumentation ; *Confidentiality ; Health Smart Cards ; Humans ; Reproducibility of Results ; Telemedicine/*instrumentation ; }, abstract = {The E-health care systems employ IT infrastructure for maximizing health care resources utilization as well as providing flexible opportunities to the remote patient. Therefore, transmission of medical data over any public networks is necessary in health care system. Note that patient authentication including secure data transmission in e-health care system is critical issue. Although several user authentication schemes for accessing remote services are available, their security analysis show that none of them are free from relevant security attacks. We reviewed Das et al.'s scheme and demonstrated their scheme lacks proper protection against several security attacks such as user anonymity, off-line password guessing attack, smart card theft attack, user impersonation attack, server impersonation attack, session key discloser attack. In order to overcome the mentioned security pitfalls, this paper proposes an anonymity preserving remote patient authentication scheme usable in E-health care systems. We then validated the security of the proposed scheme using BAN logic that ensures secure mutual authentication and session key agreement. We also presented the experimental results of the proposed scheme using AVISPA software and the results ensure that our scheme is secure under OFMC and CL-AtSe models. Moreover, resilience of relevant security attacks has been proved through both formal and informal security analysis. The performance analysis and comparison with other schemes are also made, and it has been found that the proposed scheme overcomes the security drawbacks of the Das et al.'s scheme and additionally achieves extra security requirements.}, } @article {pmid26324169, year = {2015}, author = {Amin, R and Islam, SK and Biswas, GP and Khan, MK and Obaidat, MS}, title = {Design and Analysis of an Enhanced Patient-Server Mutual Authentication Protocol for Telecare Medical Information System.}, journal = {Journal of medical systems}, volume = {39}, number = {11}, pages = {137}, pmid = {26324169}, issn = {1573-689X}, mesh = {Algorithms ; Computer Security/*instrumentation ; Confidentiality ; *Health Information Exchange ; *Health Smart Cards ; Humans ; Information Systems/instrumentation ; Telemedicine/instrumentation ; }, abstract = {In order to access remote medical server, generally the patients utilize smart card to login to the server. It has been observed that most of the user (patient) authentication protocols suffer from smart card stolen attack that means the attacker can mount several common attacks after extracting smart card information. Recently, Lu et al.'s proposes a session key agreement protocol between the patient and remote medical server and claims that the same protocol is secure against relevant security attacks. However, this paper presents several security attacks on Lu et al.'s protocol such as identity trace attack, new smart card issue attack, patient impersonation attack and medical server impersonation attack. In order to fix the mentioned security pitfalls including smart card stolen attack, this paper proposes an efficient remote mutual authentication protocol using smart card. We have then simulated the proposed protocol using widely-accepted AVISPA simulation tool whose results make certain that the same protocol is secure against active and passive attacks including replay and man-in-the-middle attacks. Moreover, the rigorous security analysis proves that the proposed protocol provides strong security protection on the relevant security attacks including smart card stolen attack. We compare the proposed scheme with several related schemes in terms of computation cost and communication cost as well as security functionalities. It has been observed that the proposed scheme is comparatively better than related existing schemes.}, } @article {pmid26305028, year = {2015}, author = {Brakke, K}, title = {STORY AND HISTORY IN FETAL BEHAVIOR RESEARCH.}, journal = {Monographs of the Society for Research in Child Development}, volume = {80}, number = {3}, pages = {114-123}, doi = {10.1111/mono.12186}, pmid = {26305028}, issn = {1540-5834}, mesh = {Female ; *Fetal Development ; *Fetal Heart ; Fetus/*embryology ; Humans ; *Maternal-Fetal Relations ; Pregnancy ; }, abstract = {In their monograph, DiPietro, Costigan, and Voegtline present an important and thoughtful portrait of low-risk fetal development during the last trimester of gestation, and they also pay tribute to the Fels Longitudinal Study investigators' early work in this area. In this commentary, the history and legacy of the Fels Institute is further explored within the broader context of fetal research, and DiPietro et al.'s findings are placed in alignment with contemporary dynamic systems' theoretical approaches that emphasize longitudinal analysis of emergent behavior and process during early development. The commentary puts forth the assertion that the work reported by DiPietro and her colleagues tells a story that sets the stage for a new generation of technology-enhanced and culturally expanded investigations of fetal behavior.}, } @article {pmid26301705, year = {2016}, author = {Černis, E and Dunn, G and Startup, H and Kingdon, D and Wingham, G and Evans, N and Lister, R and Pugh, K and Cordwell, J and Mander, H and Freeman, D}, title = {The Perseverative Thinking Questionnaire in Patients with Persecutory Delusions.}, journal = {Behavioural and cognitive psychotherapy}, volume = {44}, number = {4}, pages = {472-481}, doi = {10.1017/S1352465815000533}, pmid = {26301705}, issn = {1469-1833}, support = {G0902308/MRC_/Medical Research Council/United Kingdom ; MC_PC_11007/MRC_/Medical Research Council/United Kingdom ; MR/K006185/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Adult ; Behavior Rating Scale/standards ; Delusions/*classification/*psychology ; Female ; Humans ; Male ; Middle Aged ; Paranoid Disorders/psychology ; Pessimism/psychology ; Psychiatric Status Rating Scales ; Psychological Tests/standards ; Psychotic Disorders/psychology ; Reproducibility of Results ; Schizophrenia, Paranoid/psychology ; Surveys and Questionnaires ; }, abstract = {BACKGROUND: Ruminative negative thinking has typically been considered as a factor maintaining common emotional disorders and has recently been shown to maintain persecutory delusions in psychosis. The Perseverative Thinking Questionnaire (PTQ) (Ehring et al., 2011) is a transdiagnostic measure of ruminative negative thinking that shows promise as a "content-free" measure of ruminative negative thinking.

AIMS: The PTQ has not previously been studied in a psychosis patient group. In this study we report for the first time on the psychometric properties of Ehring et al.'s PTQ in such a group.

METHOD: The PTQ was completed by 142 patients with current persecutory delusions and 273 non-clinical participants. Participants also completed measures of worry and paranoia. A confirmatory factor analysis was performed on the clinical group's PTQ responses to assess the factor structure of the measure. Differences between groups were used to assess criterion reliability.

RESULTS: A three lower-order factor structure of the PTQ (core characteristics of ruminative negative thinking, perceived unproductiveness, and capturing mental capacity) was replicated in the clinical sample. Patients with persecutory delusions were shown to experience significantly higher levels of ruminative negative thinking on the PTQ than the general population sample. The PTQ demonstrated high internal reliability.

CONCLUSIONS: This study did not include test-retest data, and did not compare the PTQ against a measure of depressive rumination but, nevertheless, lends support for the validity of the PTQ as a measure of negative ruminative thinking in patients with psychosis.}, } @article {pmid26300841, year = {2015}, author = {Lo, S and Andrews, S}, title = {To transform or not to transform: using generalized linear mixed models to analyse reaction time data.}, journal = {Frontiers in psychology}, volume = {6}, number = {}, pages = {1171}, pmid = {26300841}, issn = {1664-1078}, abstract = {Linear mixed-effect models (LMMs) are being increasingly widely used in psychology to analyse multi-level research designs. This feature allows LMMs to address some of the problems identified by Speelman and McGann (2013) about the use of mean data, because they do not average across individual responses. However, recent guidelines for using LMM to analyse skewed reaction time (RT) data collected in many cognitive psychological studies recommend the application of non-linear transformations to satisfy assumptions of normality. Uncritical adoption of this recommendation has important theoretical implications which can yield misleading conclusions. For example, Balota et al. (2013) showed that analyses of raw RT produced additive effects of word frequency and stimulus quality on word identification, which conflicted with the interactive effects observed in analyses of transformed RT. Generalized linear mixed-effect models (GLMM) provide a solution to this problem by satisfying normality assumptions without the need for transformation. This allows differences between individuals to be properly assessed, using the metric most appropriate to the researcher's theoretical context. We outline the major theoretical decisions involved in specifying a GLMM, and illustrate them by reanalysing Balota et al.'s datasets. We then consider the broader benefits of using GLMM to investigate individual differences.}, } @article {pmid26294174, year = {2016}, author = {Palacios-González, C}, title = {The ethics of killing human/great-ape chimeras for their organs: a reply to Shaw et al.}, journal = {Medicine, health care, and philosophy}, volume = {19}, number = {2}, pages = {215-225}, pmid = {26294174}, issn = {1572-8633}, support = {/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Animals ; *Chimera ; Ethical Theory ; Humans ; *Morals ; Tissue and Organ Procurement ; }, abstract = {The aim of this paper is to critically examine David Shaw, Wybo Dondorp, and Guido de Wert's arguments in favour of the procurement of human organs from human/nonhuman-primate chimeras, specifically from great-ape/human chimeras. My main claim is that their arguments fail and are in need of substantial revision. To prove this I first introduce the topic, and then reconstruct Shaw et al.'s position and arguments. Next, I show that Shaw et al.: (1) failed to properly apply the subsidiarity and proportionality principles; (2) neglected species overlapping cases in their ethical assessment; (3) ignored the ethics literature on borderline persons; and (4) misunderstood McMahan's two-tiered moral theory. These mistakes render an important part of their conclusions either false or problematic to the point that they would no longer endorse them. Finally I will briefly mention a possible multipolar solution to the human organ shortage problem that would reduce the need for chimeras' organs.}, } @article {pmid26293169, year = {2016}, author = {Moffatt, C and Simmons, T and Lynch-Aird, J}, title = {An Improved Equation for TBS and ADD: Establishing a Reliable Postmortem Interval Framework for Casework and Experimental Studies.}, journal = {Journal of forensic sciences}, volume = {61 Suppl 1}, number = {}, pages = {S201-7}, doi = {10.1111/1556-4029.12931}, pmid = {26293169}, issn = {1556-4029}, mesh = {Autopsy ; Forensic Anthropology ; *Forensic Pathology ; Humans ; *Postmortem Changes ; Temperature ; }, abstract = {Megyesi et al.'s (J Forensic Sci, 2005, 50, 618) paper was important to forensic anthropology as it introduced a quantitative framework for estimating time since death in human cadavers, based upon physical appearance by way of scoring on a novel scale. However, errors concerning rounding, temperature scale, and incorrect use of a statistical regression model render their predictive formula unusable. Based upon only their more reliable data, a more appropriate regression model to predict accumulated degree days (ADD) from total body score (TBS) is presented. The new model is also a superior fit (r(2) = 0.91) and produces markedly narrower confidence intervals than the original, which also allowed impossible, negative ADD values. Explanations of the shortcomings in the original analysis and calculations are presented, which it is hoped will help forensic scientists avoid making similar mistakes.}, } @article {pmid26291974, year = {2018}, author = {van Breukelen, G and de Bruin, M}, title = {Incorrect interpretation of AIMS trial analyses: comment on Mathes et al.'s 'Response to letter …' (HIV Medicine 2014, 15, 383-384).}, journal = {HIV medicine}, volume = {19}, number = {1}, pages = {e43-e45}, doi = {10.1111/hiv.12282}, pmid = {26291974}, issn = {1468-1293}, mesh = {*Antiretroviral Therapy, Highly Active ; HIV ; *HIV Infections ; Humans ; }, } @article {pmid26283087, year = {2015}, author = {Cohen, AK and Lê-Scherban, F}, title = {Invited Commentary: Multigenerational Social Determinants of Health—Opportunities and Challenges.}, journal = {American journal of epidemiology}, volume = {182}, number = {7}, pages = {579-582}, doi = {10.1093/aje/kwv145}, pmid = {26283087}, issn = {1476-6256}, mesh = {*Birth Weight ; Female ; Humans ; }, abstract = {An emerging area of social epidemiology examines the relationship between grandparental education and grandchild health. In an accompanying article, Huang et al. (Am J Epidemiol. 2015;182(7):568-578) join the small but growing body of research on this topic. It is useful to contextualize Huang et al.'s work within the much larger body of research examining relationships between education and health within a single generation or across 2 generations. These investigators have generally concluded that higher educational attainment is robustly associated with better health. There are many potential mechanisms through which education and other social exposures may affect health outcomes in a single generation or across generations, and estimating direct and indirect effects can be helpful for assessing specific mechanisms. Researchers conducting multigenerational analyses are faced with several challenges, including limited availability of data for some measures (e.g., educational attainment, and sometimes for 1 grandparent only), limited age ranges of participants, disparate social and political contexts in which study participants of different generations have lived, and patterns of social class reproduction. We encourage future researchers to weave together the careful analytical considerations illustrated by Huang et al. with a rich understanding of the social context for each of the generations studied to help overcome these challenges and advance our understanding of multigenerational social determinants of health.}, } @article {pmid26263401, year = {2015}, author = {Islam, SK and Khan, MK and Li, X}, title = {Security Analysis and Improvement of 'a More Secure Anonymous User Authentication Scheme for the Integrated EPR Information System'.}, journal = {PloS one}, volume = {10}, number = {8}, pages = {e0131368}, pmid = {26263401}, issn = {1932-6203}, mesh = {*Computer Security ; *Electronic Health Records ; Humans ; *Models, Theoretical ; }, abstract = {Over the past few years, secure and privacy-preserving user authentication scheme has become an integral part of the applications of the healthcare systems. Recently, Wen has designed an improved user authentication system over the Lee et al.'s scheme for integrated electronic patient record (EPR) information system, which has been analyzed in this study. We have found that Wen's scheme still has the following inefficiencies: (1) the correctness of identity and password are not verified during the login and password change phases; (2) it is vulnerable to impersonation attack and privileged-insider attack; (3) it is designed without the revocation of lost/stolen smart card; (4) the explicit key confirmation and the no key control properties are absent, and (5) user cannot update his/her password without the help of server and secure channel. Then we aimed to propose an enhanced two-factor user authentication system based on the intractable assumption of the quadratic residue problem (QRP) in the multiplicative group. Our scheme bears more securities and functionalities than other schemes found in the literature.}, } @article {pmid26254777, year = {2015}, author = {Lertxundi, U and Isla, A and Solinis, MA and Domingo-Echaburu, S and Hernandez, R and Peral-Aguirregoitia, J and Medrano, J}, title = {Anticholinergic burden in Parkinson's disease inpatients.}, journal = {European journal of clinical pharmacology}, volume = {71}, number = {10}, pages = {1271-1277}, pmid = {26254777}, issn = {1432-1041}, mesh = {Age Factors ; Aged ; Aged, 80 and over ; Cholinergic Antagonists/*administration & dosage/adverse effects ; Cholinesterase Inhibitors/*administration & dosage/adverse effects ; Comorbidity ; Dementia/drug therapy ; Drug Utilization ; Female ; Hospitalization ; Humans ; Length of Stay ; Logistic Models ; Male ; Parkinson Disease/*drug therapy/*epidemiology ; Polypharmacy ; Sex Factors ; }, abstract = {PURPOSE: Anticholinergic toxicity can arise as a result of the cumulative burden of multiple medications and metabolites rather than be caused by a single compound. In this sense, prescribing drugs with anticholinergic properties to Parkinson's disease (PD) patients could contribute to aggravate some frequent problems of the disease, like dementia, urinary retention, falls, or constipation, among others. The main purpose of this article is to measure the total anticholinergic burden in a group of PD inpatients.

METHOD: We analyzed information from different administrative Basque Country's healthcare databases using encrypted unique identifiers in order to detect PD patients admitted to public acute care hospital during 2011-2012. Subsequently, anticholinergic burden was measured using Duran et al.'s list. Secondarily, total anticholinergic load was assessed with the Anticholinergic Drug Scale, the Anticholinergic Risk Score, and the Anticholinergic Burden Scale. A logistic regression model was performed to study association of predictive variables with anticholinergic use.

RESULTS: A high proportion of PD patients were prescribed anticholinergic drugs, with 53.6% of admissions receiving at least one drug from Duran et al.'s "low-risk" and 10% at least "high-risk" drug. Drugs used for non-motor symptoms and other comorbidities other than PD itself contributed significantly to anticholinergic burden, namely antidepressants, antipsychotics, urological drugs, analgesics, and antihistamines, among others. The total number of drugs and cholinesterase inhibitors were independently associated with anticholinergic drug use.

CONCLUSIONS: Anticholinergic burden in PD patients is significant, and is caused mostly by drugs not used for PD motor symptoms. Polypharmacy and cholinesterase inhibitors were independently associated with anticholinergic drug prescriptions.}, } @article {pmid26253598, year = {2015}, author = {Bigelow, J and Berrett, S and Kimuli, I and Katabira, E}, title = {Perceptions of epilepsy among first-year medical students at Mulago Hospital in Kampala, Uganda.}, journal = {Epilepsy & behavior : E&B}, volume = {51}, number = {}, pages = {28-32}, doi = {10.1016/j.yebeh.2015.06.020}, pmid = {26253598}, issn = {1525-5069}, mesh = {Adult ; *Epilepsy ; Female ; *Health Knowledge, Attitudes, Practice ; Humans ; Male ; *Social Stigma ; *Students, Medical ; Uganda ; Young Adult ; }, abstract = {Epilepsy is associated with stigma throughout the world, which leads to poor treatment of people with epilepsy (PWE). In Uganda, there are more than 75,000 PWE and a large treatment gap. This study evaluated the knowledge, attitudes, and practices regarding epilepsy among first-year medical students at Mulago Hospital. A 22-question survey was developed based on the previous studies of Birbeck et al.'s regarding the stigma of epilepsy in Zambia. This was administered to first-year medical students (96 respondents) at Mulago Hospital in Uganda. More than 80% said that they would not allow their children to marry PWE. Most respondents believed that epilepsy was a mental illness, and many believed that PWE cannot have normal intelligence. Students reported that there was a negative perception and negative treatment of PWE in the community. Some students believed that epilepsy was caused by supernatural causes and was contagious. These misperceptions must be identified and corrected among medical students and other healthcare providers to allow for fair treatment of PWE; this should be incorporated into medical school curriculums in Uganda.}, } @article {pmid26239693, year = {2015}, author = {Bergman, Å and Becher, G and Blumberg, B and Bjerregaard, P and Bornman, R and Brandt, I and Casey, SC and Frouin, H and Giudice, LC and Heindel, JJ and Iguchi, T and Jobling, S and Kidd, KA and Kortenkamp, A and Lind, PM and Muir, D and Ochieng, R and Ropstad, E and Ross, PS and Skakkebaek, NE and Toppari, J and Vandenberg, LN and Woodruff, TJ and Zoeller, RT}, title = {Manufacturing doubt about endocrine disrupter science--A rebuttal of industry-sponsored critical comments on the UNEP/WHO report "State of the Science of Endocrine Disrupting Chemicals 2012".}, journal = {Regulatory toxicology and pharmacology : RTP}, volume = {73}, number = {3}, pages = {1007-1017}, doi = {10.1016/j.yrtph.2015.07.026}, pmid = {26239693}, issn = {1096-0295}, mesh = {Animals ; Endocrine Disruptors/*toxicity ; Humans ; }, abstract = {We present a detailed response to the critique of "State of the Science of Endocrine Disrupting Chemicals 2012" (UNEP/WHO, 2013) by financial stakeholders, authored by Lamb et al. (2014). Lamb et al.'s claim that UNEP/WHO (2013) does not provide a balanced perspective on endocrine disruption is based on incomplete and misleading quoting of the report through omission of qualifying statements and inaccurate description of study objectives, results and conclusions. Lamb et al. define extremely narrow standards for synthesizing evidence which are then used to dismiss the UNEP/WHO 2013 report as flawed. We show that Lamb et al. misuse conceptual frameworks for assessing causality, especially the Bradford-Hill criteria, by ignoring the fundamental problems that exist with inferring causality from empirical observations. We conclude that Lamb et al.'s attempt of deconstructing the UNEP/WHO (2013) report is not particularly erudite and that their critique is not intended to be convincing to the scientific community, but to confuse the scientific data. Consequently, it promotes misinterpretation of the UNEP/WHO (2013) report by non-specialists, bureaucrats, politicians and other decision makers not intimately familiar with the topic of endocrine disruption and therefore susceptible to false generalizations of bias and subjectivity.}, } @article {pmid26238460, year = {2016}, author = {Springer, MS and Gatesy, J}, title = {The gene tree delusion.}, journal = {Molecular phylogenetics and evolution}, volume = {94}, number = {Pt A}, pages = {1-33}, doi = {10.1016/j.ympev.2015.07.018}, pmid = {26238460}, issn = {1095-9513}, mesh = {Animals ; Datasets as Topic ; Evolution, Molecular ; *Genes ; Mammals/*classification/*genetics ; *Models, Genetic ; *Phylogeny ; Polymorphism, Single Nucleotide/genetics ; Scandentia/classification/genetics ; }, abstract = {Higher-level relationships among placental mammals are mostly resolved, but several polytomies remain contentious. Song et al. (2012) claimed to have resolved three of these using shortcut coalescence methods (MP-EST, STAR) and further concluded that these methods, which assume no within-locus recombination, are required to unravel deep-level phylogenetic problems that have stymied concatenation. Here, we reanalyze Song et al.'s (2012) data and leverage these re-analyses to explore key issues in systematics including the recombination ratchet, gene tree stoichiometry, the proportion of gene tree incongruence that results from deep coalescence versus other factors, and simulations that compare the performance of coalescence and concatenation methods in species tree estimation. Song et al. (2012) reported an average locus length of 3.1 kb for the 447 protein-coding genes in their phylogenomic dataset, but the true mean length of these loci (start codon to stop codon) is 139.6 kb. Empirical estimates of recombination breakpoints in primates, coupled with consideration of the recombination ratchet, suggest that individual coalescence genes (c-genes) approach ∼12 bp or less for Song et al.'s (2012) dataset, three to four orders of magnitude shorter than the c-genes reported by these authors. This result has general implications for the application of coalescence methods in species tree estimation. We contend that it is illogical to apply coalescence methods to complete protein-coding sequences. Such analyses amalgamate c-genes with different evolutionary histories (i.e., exons separated by >100,000 bp), distort true gene tree stoichiometry that is required for accurate species tree inference, and contradict the central rationale for applying coalescence methods to difficult phylogenetic problems. In addition, Song et al.'s (2012) dataset of 447 genes includes 21 loci with switched taxonomic names, eight duplicated loci, 26 loci with non-homologous sequences that are grossly misaligned, and numerous loci with >50% missing data for taxa that are misplaced in their gene trees. These problems were compounded by inadequate tree searches with nearest neighbor interchange branch swapping and inadvertent application of substitution models that did not account for among-site rate heterogeneity. Sixty-six gene trees imply unrealistic deep coalescences that exceed 100 million years (MY). Gene trees that were obtained with better justified models and search parameters show large increases in both likelihood scores and congruence. Coalescence analyses based on a curated set of 413 improved gene trees and a superior coalescence method (ASTRAL) support a Scandentia (treeshrews)+Glires (rabbits, rodents) clade, contradicting one of the three primary systematic conclusions of Song et al. (2012). Robust support for a Perissodactyla+Carnivora clade within Laurasiatheria is also lost, contradicting a second major conclusion of this study. Song et al.'s (2012) MP-EST species tree provided the basis for circular simulations that led these authors to conclude that the multispecies coalescent accounts for 77% of the gene tree conflicts in their dataset, but many internal branches of their MP-EST tree are stunted by an order of magnitude or more due to wholesale gene tree reconstruction errors. An independent assessment of branch lengths suggests the multispecies coalescent accounts for ⩽ 15% of the conflicts among Song et al.'s (2012) 447 gene trees. Unfortunately, Song et al.'s (2012) flawed phylogenomic dataset has been used as a model for additional simulation work that suggests the superiority of shortcut coalescence methods relative to concatenation. Investigator error was passed on to the subsequent simulation studies, which also incorporated further logical errors that should be avoided in future simulation studies. Illegitimate branch length switches in the simulation routines unfairly protected coalescence methods from their Achilles' heel, high gene tree reconstruction error at short internodes. These simulations therefore provide no evidence that shortcut coalescence methods out-compete concatenation at deep timescales. In summary, the long c-genes that are required for accurate reconstruction of species trees using shortcut coalescence methods do not exist and are a delusion. Coalescence approaches based on SNPs that are widely spaced in the genome avoid problems with the recombination ratchet and merit further pursuit in both empirical systematic research and simulations.}, } @article {pmid26235820, year = {2015}, author = {Shen, B and McCaughtry, N and Martin, J and Garn, A and Kulik, N and Fahlman, M}, title = {The relationship between teacher burnout and student motivation.}, journal = {The British journal of educational psychology}, volume = {85}, number = {4}, pages = {519-532}, doi = {10.1111/bjep.12089}, pmid = {26235820}, issn = {2044-8279}, mesh = {Adolescent ; Burnout, Professional/*psychology ; Female ; Humans ; Male ; Motivation/*physiology ; Personal Autonomy ; Physical Education and Training/methods ; School Teachers ; Schools/statistics & numerical data ; Students/*psychology ; Surveys and Questionnaires ; }, abstract = {BACKGROUND: Teacher burnout is regarded as a serious problem in school settings. To date, studies on teachers' stress and burnout have largely centred on teachers' own characteristics, socialization, and behaviours, but few have explored the connection between teachers' burnout and students' motivation via their own perceptions of teachers' behaviour and emotional well-being.

AIMS: This study adopted Maslach et al.'s (2001, Annu. Rev. Psychol., 52, 397) job burnout construct and self-determination theory to investigate the relationships between teachers' burnout and students' autonomous motivation over one-semester physical education classes.

SAMPLE: A total of 1,302 high school students and their 33 physical education teachers in 20 high schools from two school districts in a major Midwest metropolitan area in the United States. The two school districts were demographically similar.

METHODS: Students and physical education teachers completed questionnaires assessing relevant psychological constructs. There were two time points for collecting students' data. One was at the beginning of a fall semester, and the other was at the end of that semester. Hierarchical linear modelling analyses were conducted.

RESULTS: It was revealed that teachers' emotional exhaustion was negatively related to students' perceived teacher autonomy support (TAS); in turn, there was a negative relationship between teachers' feeling of depersonalization and students' autonomous motivation development even when controlling for inadequate TAS.

CONCLUSION: The dimensions of teachers' burnout might play different roles in the transmission from teachers to students. Teachers' status of burnout is an important environmental factor associated with students' quality of motivation.}, } @article {pmid26233122, year = {2015}, author = {Fries, PH and Belorizky, E}, title = {Simple expressions of the nuclear relaxation rate enhancement due to quadrupole nuclei in slowly tumbling molecules.}, journal = {The Journal of chemical physics}, volume = {143}, number = {4}, pages = {044202}, doi = {10.1063/1.4926827}, pmid = {26233122}, issn = {1089-7690}, abstract = {For slowly tumbling entities or quasi-rigid lattices, we derive very simple analytical expressions of the quadrupole relaxation enhancement (QRE) of the longitudinal relaxation rate R1 of nuclear spins I due to their intramolecular magnetic dipolar coupling with quadrupole nuclei of arbitrary spins S ≥ 1. These expressions are obtained by using the adiabatic approximation for evaluating the time evolution operator of the quantum states of the quadrupole nuclei S. They are valid when the gyromagnetic ratio of the spin S is much smaller than that of the spin I. The theory predicts quadrupole resonant peaks in the dispersion curve of R1 vs magnetic field. The number, positions, relative intensities, Lorentzian shapes, and widths of these peaks are explained in terms of the following properties: the magnitude of the quadrupole Hamiltonian and the asymmetry parameter of the electric field gradient (EFG) acting on the spin S, the S-I inter-spin orientation with respect to the EFG principal axes, the rotational correlation time of the entity carrying the S-I pair, and/or the proper relaxation time of the spin S. The theory is first applied to protein amide protons undergoing dipolar coupling with fast-relaxing quadrupole (14)N nuclei and mediating the QRE to the observed bulk water protons. The theoretical QRE agrees well with its experimental counterpart for various systems such as bovine pancreatic trypsin inhibitor and cartilages. The anomalous behaviour of the relaxation rate of protons in synthetic aluminium silicate imogolite nano-tubes due to the QRE of (27)Al (S = 5/2) nuclei is also explained.}, } @article {pmid26219346, year = {2015}, author = {Chang, HY and Shyu, YI and Wong, MK and Friesner, D and Chu, TL and Teng, CI}, title = {Which Aspects of Professional Commitment Can Effectively Retain Nurses in the Nursing Profession?.}, journal = {Journal of nursing scholarship : an official publication of Sigma Theta Tau International Honor Society of Nursing}, volume = {47}, number = {5}, pages = {468-476}, doi = {10.1111/jnu.12152}, pmid = {26219346}, issn = {1547-5069}, mesh = {Adult ; *Attitude of Health Personnel ; Female ; Humans ; Job Satisfaction ; Longitudinal Studies ; Male ; Middle Aged ; Motivation ; Nursing Staff, Hospital/*psychology/supply & distribution ; *Personnel Loyalty ; Personnel Turnover ; *Professional Competence ; Psychometrics ; Surveys and Questionnaires ; Taiwan ; Young Adult ; }, abstract = {PURPOSE: This study examined which aspects of professional commitment can effectively retain nurses in the nursing profession.

This study used a longitudinal design, simple random sampling, and two-wave data collection to survey and follow up a representative sample of 579 nurses for 1 year in a major medical center in northern Taiwan.

METHODS: Items measuring each aspect of professional commitment came from Meyer et al.'s scale. In the second wave, administrative data were culled to determine whether these nurses remain employed as nurses. Structural equation modeling is used to analyze the data.

RESULTS: Analytical results indicate that continuance commitment predicts nurse retention in the nursing profession (path coefficient = 0.34, p < .01).

CONCLUSIONS: Institutional efforts to improve continuance commitment (e.g., improved salary structures and enhanced professional development opportunities) likely retain nurses in the nursing profession.

CLINICAL RELEVANCE: The findings of this study indicate the importance of continuance intention in retaining nurses. Nursing managers who face staff retention issues may consider making efforts to improve nurse salary and employer-sponsored benefits.}, } @article {pmid26214567, year = {2015}, author = {Falcon, RG}, title = {Is envy categorical or dimensional? An empirical investigation using taxometric analysis.}, journal = {Emotion (Washington, D.C.)}, volume = {15}, number = {6}, pages = {694-698}, doi = {10.1037/emo0000102}, pmid = {26214567}, issn = {1931-1516}, mesh = {Adolescent ; Adult ; Female ; Humans ; *Jealousy ; Male ; Middle Aged ; Models, Psychological ; Young Adult ; }, abstract = {Researchers frequently disagree about the latent structure of emotions. Taxometric analysis--a method for determining whether the latent structure of a construct is best defined as categorical or purely dimensional--can be a useful tool for resolving these debates. The present study used taxometric analysis to investigate the latent structure of envy. Scholars disagree about whether envy is necessarily malicious or whether it can also be benign. Van de Ven, Zeelenberg, and Pieters (2009) claim that benign envy exists, and that it is distinct from malicious envy. Much of their evidence for this claim relies on latent class analysis, which can be biased toward creating categories with data that actually vary dimensionally (Cleland, Rothschild, & Haslam, 2000; Uebersax, 1999). Therefore, taxometric analysis provides a more conservative test for an underlying categorical structure. A daily diary procedure was used to measure participants' day-to-day experiences of envy. The results support van de Ven et al.'s claim that benign envy exists, and that is distinct from malicious envy.}, } @article {pmid26201078, year = {2015}, author = {Schauerte, B and Stiefelhagen, R}, title = {On the Distribution of Salient Objects in Web Images and Its Influence on Salient Object Detection.}, journal = {PloS one}, volume = {10}, number = {7}, pages = {e0130316}, pmid = {26201078}, issn = {1932-6203}, mesh = {Algorithms ; Attention/*physiology ; Fixation, Ocular/*physiology ; Humans ; Models, Statistical ; Normal Distribution ; Photic Stimulation ; Visual Perception/physiology ; }, abstract = {In recent years it has become apparent that a Gaussian center bias can serve as an important prior for visual saliency detection, which has been demonstrated for predicting human eye fixations and salient object detection. Tseng et al. have shown that the photographer's tendency to place interesting objects in the center is a likely cause for the center bias of eye fixations. We investigate the influence of the photographer's center bias on salient object detection, extending our previous work. We show that the centroid locations of salient objects in photographs of Achanta and Liu's data set in fact correlate strongly with a Gaussian model. This is an important insight, because it provides an empirical motivation and justification for the integration of such a center bias in salient object detection algorithms and helps to understand why Gaussian models are so effective. To assess the influence of the center bias on salient object detection, we integrate an explicit Gaussian center bias model into two state-of-the-art salient object detection algorithms. This way, first, we quantify the influence of the Gaussian center bias on pixel- and segment-based salient object detection. Second, we improve the performance in terms of F1 score, Fβ score, area under the recall-precision curve, area under the receiver operating characteristic curve, and hit-rate on the well-known data set by Achanta and Liu. Third, by debiasing Cheng et al.'s region contrast model, we exemplarily demonstrate that implicit center biases are partially responsible for the outstanding performance of state-of-the-art algorithms. Last but not least, we introduce a non-biased salient object detection method, which is of interest for applications in which the image data is not likely to have a photographer's center bias (e.g., image data of surveillance cameras or autonomous robots).}, } @article {pmid26194045, year = {2015}, author = {Rajabally, YA and Hiew, FL and Winer, JB}, title = {Influence of timing on electrodiagnosis of Guillain-Barré syndrome in the first six weeks: a retrospective study.}, journal = {Journal of the neurological sciences}, volume = {357}, number = {1-2}, pages = {143-145}, doi = {10.1016/j.jns.2015.07.018}, pmid = {26194045}, issn = {1878-5883}, mesh = {Adult ; Aged ; Electrodiagnosis/*methods ; Female ; Guillain-Barre Syndrome/*diagnosis/*physiopathology ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Time Factors ; }, abstract = {The effect of timing is uncertain on the electrophysiology of Guillain-Barré syndrome (GBS). On this may however depend the usefulness of systematic serial studies performed at specific time intervals. We retrospectively analyzed records of 118 consecutive patients with GBS from Birmingham, U.K. (2001-2012), studied between 0-14days, or, 15-42days post-onset using new criteria which we recently proposed [4]. Rates of acute inflammatory demyelinating polyneuropathy (AIDP) (p=0.45), axonal GBS (p=0.32) and equivocal forms (p=0.46) were similar for both timings. Similarly, no significant differences between timings were observed using Hadden et al.'s criteria. Proportions were comparable to published serial studies for both timings, for AIDP (p=0.25; p=0.10) and axonal GBS (p=0.73; p=0.56) but were higher than with serial studies for equivocal forms in patients studied on days 0-14 (p=0.012), although not in those studied on days 15-42 (p=0.17). This suggests that over the initial 6weeks post-onset, timing fails to influence subtype proportions in a large GBS cohort, irrespective of criteria used. Repeat studies appear therefore unlikely to be helpful when systematically performed within this time frame, except in equivocal cases. The benefit of repeat studies remains possible at other times but may need to be individualized, and requires future prospective evaluation.}, } @article {pmid26164359, year = {2015}, author = {Soares, CB and Figueiroa, JN and Dantas, RM and Kurita, LM and Pontual, Ados A and Ramos-Perez, FM and Perez, DE and Pontual, ML}, title = {Evaluation of third molar development in the estimation of chronological age.}, journal = {Forensic science international}, volume = {254}, number = {}, pages = {13-17}, doi = {10.1016/j.forsciint.2015.06.022}, pmid = {26164359}, issn = {1872-6283}, mesh = {Adolescent ; Age Determination by Teeth/*methods ; Brazil ; Child ; Female ; Humans ; Linear Models ; Male ; Molar, Third/*diagnostic imaging/*growth & development ; Radiography, Panoramic ; Reproducibility of Results ; *Tooth Calcification ; Young Adult ; }, abstract = {The purpose of this study was to evaluate the correlation between chronological age and the degree of third molar mineralization by Demirjian's developmental stages (Demirjian et al., 1973) using panoramic radiography. From a total of 11.396 digital panoramic radiographs of patients from three oral radiology private clinics from the northeast region of Brazil, obtained from January to June 2009, 2097 radiographic images from patients aged between 6 and 22 years were selected. The images were analyzed individually by two obsevers using a 21-inch computer screen and Windows Picture and Fax Viewer. Reliability was achieved by intra- and interobserver evaluation, using the Kappa test. Chronological age, calcification stage, gender and third molar were interrelated using a multiple linear regression model, considering age as a response variable. There was reliability with Demirjian et al.'s developmental stage assesment, displaying a significant relationship between mineralization stages and patients' age (P<0.05). There was no significant difference between the average age and the calcification stage taking gender and localization of the third molar into consideration. It is possible to estimate chronological age based on Demirjian's stage of a third molar, regardless of gender and location.}, } @article {pmid27774228, year = {2015}, author = {Maslen, H and Douglas, T and Cohen Kadosh, R and Levy, N and Savulescu, J}, title = {The regulation of cognitive enhancement devices: refining Maslen et al.'s model.}, journal = {Journal of law and the biosciences}, volume = {2}, number = {3}, pages = {754-767}, doi = {10.1093/jlb/lsv029}, pmid = {27774228}, issn = {2053-9711}, abstract = {Our (2014) model for the regulation of cognitive enhancement devices (CEDs) received a great deal of interest from those involved in European device regulation and from academic commentators. Further, since the publication of our recommendations, the number of manufacturers of brain stimulation devices for non-medical purposes has increased, underscoring the need for a regulatory response. In this paper, we clarify aspects of our original proposal and address additional regulatory issues beyond our original focus on the sale of devices. We begin with theoretical points pertaining to the definition of a CED and the distinction between treatment and enhancement. We then respond to practical challenges raised by the prospect of implementing our regulatory framework. Next, we address some wider societal considerations relating to users and other stakeholders. Finally, we revisit the broader regulatory context within which the various discussions are situated.}, } @article {pmid26147667, year = {2015}, author = {Bhatia, JS and Oaksford, M}, title = {Discounting testimony with the argument ad hominem and a Bayesian congruent prior model.}, journal = {Journal of experimental psychology. Learning, memory, and cognition}, volume = {41}, number = {5}, pages = {1548-1559}, doi = {10.1037/xlm0000151}, pmid = {26147667}, issn = {1939-1285}, mesh = {Adult ; *Bayes Theorem ; Culture ; *Dissent and Disputes ; Female ; Humans ; Judgment/*physiology ; *Logic ; Male ; *Models, Psychological ; *Social Perception ; Young Adult ; }, abstract = {When directed to ignore evidence of a witness's previous bad character because of a violation of the rules of evidence, are jurors' beliefs still affected? The intuition is that they will be because in everyday argumentation, fallacies, like the ad hominem, are effective argumentative strategies. An ad hominem argument (against the person) undermines a conclusion by questioning the character of the proposer. This intuition divides current theories of argumentation. According to pragmadialectical theory (e.g., Van Eemeren & Grootendorst, 2004), procedural rules exactly like the rules of evidence are part of our cognitive resources for evaluating arguments. If one of these rules is violated, an argument should be treated as a fallacy and so it should not alter someone's belief in the conclusion. Some recent experiments investigating how reasonable these arguments are perceived to be seem to support this account (van Eemeren, Garssen, & Meuffels, 2009). These experiments are critiqued from the perspective of the relevance (Walton, 2009, 2010) and epistemic (Hahn & Oaksford, 2006, 2007; Oaksford & Hahn, 2004) approaches to argumentation. An experiment investigates the predictions of these approaches for a graded belief change version of van Eemeren et al.'s (2009) experiment, and the results are modeled using a Bayesian congruent prior model. These results cannot be explained by the pragmadialectical approach and show that in everyday argument people are extremely sensitive to the epistemic relevance of evidence. Moreover, it seems highly unlikely that this can be switched off in more formal contexts such as the courtroom.}, } @article {pmid27703907, year = {2015}, author = {Wilczynski, SM}, title = {The Emperor Just Might Be Wearing Pants.}, journal = {Behavior analysis in practice}, volume = {8}, number = {2}, pages = {147-148}, pmid = {27703907}, issn = {1998-1929}, abstract = {This is a commentary in response to Dixon et al.'s (Behavior Analysis and Practice, 8(1), 7-15, 2015) article entitled, "Research rankings of behavior analytic graduate training programs and their faculty" in Behavior Analysis in Practice. The severe restriction of range for the metric used to identify faculty productivity and knowledge of research calls the implications drawn from the data into question. Suggestions on how to broaden the metric are made along with implications for doing so. This is an important topic, and many people will need to contribute to a robust conversation about our graduate training programs given the exponential growth we have faced in recent decades.}, } @article {pmid26123833, year = {2015}, author = {Amin, R and Biswas, GP}, title = {An Improved RSA Based User Authentication and Session Key Agreement Protocol Usable in TMIS.}, journal = {Journal of medical systems}, volume = {39}, number = {8}, pages = {79}, pmid = {26123833}, issn = {1573-689X}, mesh = {Algorithms ; Computer Security/*instrumentation ; Confidentiality ; Humans ; Information Systems/*instrumentation ; Telemedicine/*instrumentation ; }, abstract = {Recently, Giri et al.'s proposed a RSA cryptosystem based remote user authentication scheme for telecare medical information system and claimed that the protocol is secure against all the relevant security attacks. However, we have scrutinized the Giri et al.'s protocol and pointed out that the protocol is not secure against off-line password guessing attack, privileged insider attack and also suffers from anonymity problem. Moreover, the extension of password guessing attack leads to more security weaknesses. Therefore, this protocol needs improvement in terms of security before implementing in real-life application. To fix the mentioned security pitfalls, this paper proposes an improved scheme over Giri et al.'s scheme, which preserves user anonymity property. We have then simulated the proposed protocol using widely-accepted AVISPA tool which ensures that the protocol is SAFE under OFMC and CL-AtSe models, that means the same protocol is secure against active and passive attacks including replay and man-in-the-middle attacks. The informal cryptanalysis has been also presented, which confirmed that the proposed protocol provides well security protection on the relevant security attacks. The performance analysis section compares the proposed protocol with other existing protocols in terms of security and it has been observed that the protocol provides more security and achieves additional functionalities such as user anonymity and session key verification.}, } @article {pmid26103114, year = {2015}, author = {Simoes Loureiro, I and Lefebvre, L}, title = {[The SQK: a semantic knowledge questionnaire to specify the severity of semantic deterioration in Alzheimer's disease patients].}, journal = {Geriatrie et psychologie neuropsychiatrie du vieillissement}, volume = {13}, number = {2}, pages = {225-233}, doi = {10.1684/pnv.2015.0535}, pmid = {26103114}, issn = {2115-7863}, mesh = {Aged ; Aged, 80 and over ; Alzheimer Disease/*diagnosis/*psychology ; Disease Progression ; Female ; Humans ; *Language Tests ; Male ; Memory ; Memory Disorders/psychology ; Neuropsychological Tests ; Semantics ; Severity of Illness Index ; *Vocabulary ; }, abstract = {Lexico-semantic difficulties are common in Alzheimer's disease (AD). The bottom-up process theory is today well accepted: superordinate attributes tend to decline slower than subordinate ones. However, a specific issue in semantic memory investigation in AD is to determine the severity of the semantic impairment. Given that the regularity of the semantic disorder in early AD is uncertain, we argue that the constitution of experimental AD groups must consider the semantic deterioration stage. We thus propose a specific semantic knowledge questionnaire (SKQ), based on Laiacona et al.'s work (1993). SKQ was proposed to 49 AD patients and 33 healthy old people. Three experimental AD groups were created, based on the global cognitive deterioration. In a second study, we explore the possibility for early AD to display different semantic deterioration profile. Our results show a significant group effect, a significant type of question effect (superordinate vs subordinate) and a significant interaction effect. Moreover, a significant correlation between the total errors at the SKQ and the MMSE score is observed. Finally, we observe that early AD patients can show different semantic alteration, with mild or very mild semantic deterioration without any differences in the global cognitive alteration. The SKQ seems adapted to highlight the semantic deterioration and the bottom-up process in AD: superordinate information are better preserved than subordinate information. It can also distinguish different semantic deterioration in early AD. Our result clearly show that research on semantic deterioration in early stage of AD must take into account the severity of the semantic alteration.}, } @article {pmid26102518, year = {2015}, author = {Rybnikova, N and Haim, A and Portnov, BA}, title = {Artificial Light at Night (ALAN) and breast cancer incidence worldwide: A revisit of earlier findings with analysis of current trends.}, journal = {Chronobiology international}, volume = {32}, number = {6}, pages = {757-773}, doi = {10.3109/07420528.2015.1043369}, pmid = {26102518}, issn = {1525-6073}, mesh = {Breast Neoplasms/diagnosis/*epidemiology ; Circadian Rhythm ; Databases, Factual ; Diet ; Female ; Global Health ; Humans ; Incidence ; Life Style ; *Light ; Lighting/*adverse effects ; Models, Statistical ; Risk Factors ; Urban Population ; }, abstract = {In a study published in Cancer Causes & Control in 2010, Kloog with co-authors tested, apparently for the first time, the association between population-level ambient exposure to artificial light at night (ALAN) and incidence of several cancers in women from 164 countries worldwide. The study was based on 1996-2002 data and concluded that breast cancer (BC) incidence was significantly and positively associated with ALAN, while no such association was revealed for other cancer types. An open question, however, remains whether the trends revealed by Kloog and co-authors were time specific or also hold true for more recent data. Using information obtained from the GLOBOCAN, US-DMSP and World Bank's 2002 and 2012 databases, we reanalyzed the strength of association between BC incidence rates in 180 countries worldwide and ALAN, controlling for several country-level predictors, including birth rates, percent of urban population, per capita GDP and electricity consumption. We also compared BC age-standardized rates (ASRs) with multi-annual ALAN measurements, considering potentially different latency periods. Compared with the results of Kloog et al.'s analysis of the year-2002 BC-data, the association between BC and ALAN appears to have weakened overall, becoming statistically insignificant in the year 2012 after being controlled for potential confounders (t < 0.3; p > 0.5). However, when the entire sample of countries was disaggregated into geographic clusters of similarly developed countries, a positive BC-ALAN association re-emerged as statistically significant (t > 2.2; p < 0.01), helping to explain, along with other factors covered by the analysis, about 65-85% of BC ASR variability worldwide, depending on the model type. Although the present analysis reconfirms a positive BC-ALAN association, this association appeared to diverge regionally in recent years, with countries in Western Europe showing the highest levels of such association, while countries in Southeast Asia and Gulf States exhibiting relatively low BC rates against the backdrop of relatively high ALAN levels. This regional stratification may be due to additional protective mechanisms, diminishing BC risks and potentially attributed to the local diet and lifestyles.}, } @article {pmid26095891, year = {2015}, author = {Culbert, KM and Racine, SE and Klump, KL}, title = {Research Review: What we have learned about the causes of eating disorders - a synthesis of sociocultural, psychological, and biological research.}, journal = {Journal of child psychology and psychiatry, and allied disciplines}, volume = {56}, number = {11}, pages = {1141-1164}, doi = {10.1111/jcpp.12441}, pmid = {26095891}, issn = {1469-7610}, mesh = {*Feeding and Eating Disorders/etiology/genetics/physiopathology ; Humans ; }, abstract = {BACKGROUND: Eating disorders are severe psychiatric disorders with a complex etiology involving transactions among sociocultural, psychological, and biological influences. Most research and reviews, however, focus on only one level of analysis. To address this gap, we provide a qualitative review and summary using an integrative biopsychosocial approach.

METHODS: We selected variables for which there were available data using integrative methodologies (e.g., twin studies, gene-environment interactions) and/or data at the biological and behavioral level (e.g., neuroimaging). Factors that met these inclusion criteria were idealization of thinness, negative emotionality, perfectionism, negative urgency, inhibitory control, cognitive inflexibility, serotonin, dopamine, ovarian hormones. Literature searches were conducted using PubMed. Variables were classified as risk factors or correlates of eating disorder diagnoses and disordered eating symptoms using Kraemer et al.'s (1997) criteria.

FINDINGS: Sociocultural idealization of thinness variables (media exposure, pressures for thinness, thin-ideal internalization, thinness expectancies) and personality traits (negative emotionality, perfectionism, negative urgency) attained 'risk status' for eating disorders and/or disordered eating symptoms. Other factors were identified as correlates of eating pathology or were not classified given limited data. Effect sizes for risk factors and correlates were generally small-to-moderate in magnitude.

CONCLUSIONS: Multiple biopsychosocial influences are implicated in eating disorders and/or disordered eating symptoms and several can now be considered established risk factors. Data suggest that psychological and environmental factors interact with and influence the expression of genetic risk to cause eating pathology. Additional studies that examine risk variables across multiple levels of analysis and that consider specific transactional processes amongst variables are needed to further elucidate the intersection of sociocultural, psychological, and biological influences on eating disorders.}, } @article {pmid26092044, year = {2016}, author = {Leising, D and Locke, KD and Kurzius, E and Zimmermann, J}, title = {Quantifying the Association of Self-Enhancement Bias With Self-Ratings of Personality and Life Satisfaction.}, journal = {Assessment}, volume = {23}, number = {5}, pages = {588-602}, doi = {10.1177/1073191115590852}, pmid = {26092044}, issn = {1552-3489}, mesh = {Adult ; *Bias ; *Ego ; Female ; Humans ; Male ; Models, Psychological ; *Personal Satisfaction ; *Personality ; Personality Tests ; Social Desirability ; }, abstract = {Kwan, John, Kenny, Bond, and Robins conceptualize self-enhancement as a favorable comparison of self-judgments with judgments of and by others. Applying a modified version of Kwan et al.'s approach to behavior observation data, we show that the resulting measure of self-enhancement bias is highly reliable, predicts self-ratings of intelligence as well as does actual intelligence, interacts with item desirability in predicting responses to questionnaire items, and also predicts general life satisfaction. Consistent with previous research, however, self-ratings of intelligence did not become more valid when controlling for self-enhancement bias. We also show that common personality scales like the Rosenberg Self-Esteem Scale reflect self-enhancement at least as strongly as do scales that were designed particularly for that purpose (i.e., "social desirability scales"). The relevance of these findings in regard to the validity and utility of social desirability scales is discussed.}, } @article {pmid26084587, year = {2015}, author = {Li, CT and Weng, CY and Lee, CC}, title = {A Secure RFID Tag Authentication Protocol with Privacy Preserving in Telecare Medicine Information System.}, journal = {Journal of medical systems}, volume = {39}, number = {8}, pages = {77}, pmid = {26084587}, issn = {1573-689X}, mesh = {Computer Security/*instrumentation ; Confidentiality ; Humans ; Information Systems/*instrumentation ; *Radio Frequency Identification Device ; Telemedicine/*instrumentation ; }, abstract = {Radio Frequency Identification (RFID) based solutions are widely used for providing many healthcare applications include patient monitoring, object traceability, drug administration system and telecare medicine information system (TMIS) etc. In order to reduce malpractices and ensure patient privacy, in 2015, Srivastava et al. proposed a hash based RFID tag authentication protocol in TMIS. Their protocol uses lightweight hash operation and synchronized secret value shared between back-end server and tag, which is more secure and efficient than other related RFID authentication protocols. Unfortunately, in this paper, we demonstrate that Srivastava et al.'s tag authentication protocol has a serious security problem in that an adversary may use the stolen/lost reader to connect to the medical back-end server that store information associated with tagged objects and this privacy damage causing the adversary could reveal medical data obtained from stolen/lost readers in a malicious way. Therefore, we propose a secure and efficient RFID tag authentication protocol to overcome security flaws and improve the system efficiency. Compared with Srivastava et al.'s protocol, the proposed protocol not only inherits the advantages of Srivastava et al.'s authentication protocol for TMIS but also provides better security with high system efficiency.}, } @article {pmid26082281, year = {2015}, author = {Hesslinger, VM and Goldbach, L and Carbon, CC}, title = {Men in red: A reexamination of the red-attractiveness effect.}, journal = {Psychonomic bulletin & review}, volume = {22}, number = {4}, pages = {1142-1148}, pmid = {26082281}, issn = {1531-5320}, mesh = {Adolescent ; Adult ; *Color ; Female ; Humans ; Male ; Middle Aged ; Perception ; Reproducibility of Results ; *Social Perception ; Young Adult ; }, abstract = {Elliot, Kayser, Greitemeyer, Lichtenfeld, Gramzow, Maier, and Liu (Journal of Experimental Psychology: General, 139(3), 399-417, 2010) showed that presenting men in front of a red background or with a red shirt enhances their attractiveness, sexual desirability, and status in the eyes of female observers. The purpose of the present research was to gain further insights concerning the robustness and the ecological validity of this red effect. In two experiments, we replicated the basic paradigm used by Elliot et al. Experiment 1 was a close replication of the first experiment in their original series. We presented the photo of a young man used by Elliot et al. on either a red or white background and asked participants (N = 89, female subsample n = 72) to rate it with regard to perceived attractiveness. Experiment 2 (N = 32) represents a somewhat more complex version of the first experiment; we increased the variance of the stimuli by showing photos of multiple men wearing different apparel styles (formal and casual, respectively). We did not find any significant impact of red in either of the studies. What we found, however, was a significant effect of apparel style with attractiveness ratings being higher for men wearing formal apparel than for men wearing casual apparel. Our results question the robustness and the ecological validity of Elliot et al.'s finding. On a more general level, they further point to limitations arising from (often necessary) restrictions in experimental designs.}, } @article {pmid26079273, year = {2015}, author = {Peterson, CC and Slaughter, V and Brownell, C}, title = {Children with autism spectrum disorder are skilled at reading emotion body language.}, journal = {Journal of experimental child psychology}, volume = {139}, number = {}, pages = {35-50}, doi = {10.1016/j.jecp.2015.04.012}, pmid = {26079273}, issn = {1096-0457}, mesh = {Autism Spectrum Disorder/*psychology ; Child ; Child Development/physiology ; Child, Preschool ; Emotions/*physiology ; Empathy/*physiology ; Female ; Humans ; *Kinesics ; Male ; Neuropsychological Tests ; Theory of Mind/*physiology ; }, abstract = {Autism is commonly believed to impair the ability to perceive emotions, yet empirical evidence is mixed. Because face processing may be difficult for those with autism spectrum disorder (ASD), we developed a novel test of recognizing emotion via static body postures (Body-Emotion test) and evaluated it with children aged 5 to 12 years in two studies. In Study 1, 34 children with ASD and 41 typically developing (TD) controls matched for age and verbal intelligence (VIQ [verbal IQ]) were tested on (a) our new Body-Emotion test, (b) a widely used test of emotion recognition using photos of eyes as stimuli (Baron-Cohen et al.'s "Reading Mind in the Eyes: Child" or RMEC [Journal of Developmental and Learning Disorders, 2001, Vol. 5, pp. 47-78]), (c) a well-validated theory of mind (ToM) battery, and (d) a teacher-rated empathy scale. In Study 2 (33 children with ASD and 31 TD controls), the RMEC test was simplified to the six basic human emotions. Results of both studies showed that children with ASD performed as well as their TD peers on the Body-Emotion test. Yet TD children outperformed the ASD group on ToM and on both the standard RMEC test and the simplified version. VIQ was not related to perceiving emotions via either body posture or eyes for either group. However, recognizing emotions from body posture was correlated with ToM, especially for children with ASD. Finally, reading emotions from body posture was easier than reading emotions from eyes for both groups.}, } @article {pmid26072754, year = {2015}, author = {Yang, Z and Yu, G and Wang, H and Lu, Q and Xu, X}, title = {Modeling of diode pumped metastable rare gas lasers.}, journal = {Optics express}, volume = {23}, number = {11}, pages = {13823-13832}, doi = {10.1364/OE.23.013823}, pmid = {26072754}, issn = {1094-4087}, abstract = {As a new kind of optically pumped gaseous lasers, diode pumped metastable rare gas lasers (OPRGLs) show potential in high power operation. In this paper, a multi-level rate equation based model of OPRGL is established. A qualitative agreement between simulation and Rawlins et al.'s experimental result shows the validity of the model. The key parameters' influences and energy distribution characteristics are theoretically studied, which is useful for the optimized design of high efficient OPRGLs.}, } @article {pmid26070819, year = {2014}, author = {Ogundana, OM and Ajayi, OF and Odukoya, O}, title = {Analysis of Elastic Tissue in Histological Variants of Pleomorphic Salivary Adenoma seen at the Lagos University Teaching Hospital over a period of 35 Years.}, journal = {West African journal of medicine}, volume = {33}, number = {3}, pages = {167-171}, pmid = {26070819}, issn = {0189-160X}, mesh = {Adenoma, Pleomorphic/classification/epidemiology/*pathology ; Adolescent ; Adult ; Biopsy ; Child ; Elastic Tissue/*pathology ; Female ; *Forecasting ; Hospitals, University/*statistics & numerical data ; Humans ; Incidence ; Male ; Middle Aged ; Nigeria/epidemiology ; Photomicrography ; Retrospective Studies ; Salivary Gland Neoplasms/classification/epidemiology/*pathology ; Young Adult ; }, abstract = {BACKGROUND: Pleomorphic salivary adenoma (PSA), is known for its morphologic diversity. While reports of elastic tissue in PSA have been documented, the distribution of this tissue in histological variants of the tumour has not been documented. Perhaps such features may influence biological behaviour of these variants.

OBJECTIVE: To classify PSA in our series into histological variants, and determine possible variation in elastic tissue distribution in them.

METHODS: Eighty eight histologically diagnosed cases of PSA in the oral biopsy archives of the department of Oral Biology and Pathology, Lagos University Teaching Hospital, were retrieved. New H&E sections were cut to reconfirm diagnosis and Verhoeff-Van Gieson's stained sections were cut for demonstration of elastic tissue. Seifert et al.'s (1976) histological classification was applied and elastic tissue presence was determined and quantified for each case. Parameters studied included; sex, age, site, histological subtypes and presence of elastic tissue. Statistical analysis was undertaken using the EPI-INFO version 3.4.

RESULTS: Male:female ratio was 1:1.3. Most cases (63.6%) occurred in the age group of 21-40 years. Generally, palate (42.0%) was the most commonly affected site, while 53.4% of cases were in the minor salivary glands. Seifert et al. classified subtype II lesions were the most frequently observed (39.7%) and elastic tissue was confirmed in 91.0% of cases. No association was noted between proportion of elastic tissue and histological variants.

CONCLUSION: Seifert et al subtype II was the most frequently observed and no association was observed between proportion of elastic tissue and the histological variant of PSA.}, } @article {pmid26061705, year = {2015}, author = {Miller, S and Knowles, J}, title = {Population Fluctuation Promotes Cooperation in Networks.}, journal = {Scientific reports}, volume = {5}, number = {}, pages = {11054}, pmid = {26061705}, issn = {2045-2322}, mesh = {*Cooperative Behavior ; *Game Theory ; Humans ; *Models, Theoretical ; }, abstract = {We consider the problem of explaining the emergence and evolution of cooperation in dynamic network-structured populations. Building on seminal work by Poncela et al., which shows how cooperation (in one-shot prisoner's dilemma) is supported in growing populations by an evolutionary preferential attachment (EPA) model, we investigate the effect of fluctuations in the population size. We find that a fluctuating model - based on repeated population growth and truncation - is more robust than Poncela et al.'s in that cooperation flourishes for a wider variety of initial conditions. In terms of both the temptation to defect, and the types of strategies present in the founder network, the fluctuating population is found to lead more securely to cooperation. Further, we find that this model will also support the emergence of cooperation from pre-existing non-cooperative random networks. This model, like Poncela et al.'s, does not require agents to have memory, recognition of other agents, or other cognitive abilities, and so may suggest a more general explanation of the emergence of cooperation in early evolutionary transitions, than mechanisms such as kin selection, direct and indirect reciprocity.}, } @article {pmid26059109, year = {2015}, author = {Lyimo, CM and Weigend, A and Msoffe, PL and Hocking, PM and Simianer, H and Weigend, S}, title = {Maternal genealogical patterns of chicken breeds sampled in Europe.}, journal = {Animal genetics}, volume = {46}, number = {4}, pages = {447-451}, doi = {10.1111/age.12304}, pmid = {26059109}, issn = {1365-2052}, mesh = {Animals ; *Breeding ; Chickens/*genetics ; DNA, Mitochondrial/genetics ; Europe ; Evolution, Molecular ; Female ; *Genetics, Population ; Haplotypes ; Molecular Sequence Data ; *Polymorphism, Genetic ; Sequence Analysis, DNA ; }, abstract = {The aim of this study was to investigate the maternal genealogical pattern of chicken breeds sampled in Europe. Sequence polymorphisms of 1256 chickens of the hypervariable region (D-loop) of mitochondrial DNA (mtDNA) were used. Median-joining networks were constructed to establish evolutionary relationships among mtDNA haplotypes of chickens, which included a wide range of breeds with different origin and history. Chicken breeds which have had their roots in Europe for more than 3000 years were categorized by their founding regions, encompassing Mediterranean type, East European type and Northwest European type. Breeds which were introduced to Europe from Asia since the mid-19th century were classified as Asian type, and breeds based on crossbreeding between Asian breeds and European breeds were classified as Intermediate type. The last group, Game birds, included fighting birds from Asia. The classification of mtDNA haplotypes was based on Liu et al.'s (2006) nomenclature. Haplogroup E was the predominant clade among the European chicken breeds. The results showed, on average, the highest number of haplotypes, highest haplotype diversity, and highest nucleotide diversity for Asian type breeds, followed by Intermediate type chickens. East European and Northwest European breeds had lower haplotype and nucleotide diversity compared to Mediterranean, Intermediate, Game and Asian type breeds. Results of our study support earlier findings that chicken breeds sampled in Europe have their roots in the Indian subcontinent and East Asia. This is consistent with historical and archaeological evidence of chicken migration routes to Europe.}, } @article {pmid26058502, year = {2015}, author = {Verity, C and Philip, S and Martland, T and Carter, M and Varadkar, S and Harkness, W and Cross, H and Walsh, R}, title = {Misleading data in Shastin et al.'s paper.}, journal = {Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery}, volume = {31}, number = {7}, pages = {1017-1018}, pmid = {26058502}, issn = {1433-0350}, mesh = {Epilepsy/*surgery ; Female ; Humans ; Male ; Management Audit/*methods/*trends ; Neurophysiological Monitoring/*methods ; Neurosurgical Procedures/*methods ; }, } @article {pmid26050699, year = {2015}, author = {Kimbrel, NA and Meyer, EC and Beckham, JC}, title = {A clinician's perspective on memory reconsolidation as the primary basis for psychotherapeutic change in posttraumatic stress disorder (PTSD).}, journal = {The Behavioral and brain sciences}, volume = {38}, number = {}, pages = {e8}, pmid = {26050699}, issn = {1469-1825}, support = {I01 RX000304/RX/RRD VA/United States ; IK2 CX000525/CX/CSRD VA/United States ; }, mesh = {Humans ; *Memory ; *Stress Disorders, Post-Traumatic ; }, abstract = {Lane et al.'s proposal that psychotherapeutic change comes about through memory reconsolidation is compelling; however, the model would be strengthened by the inclusion of predictions regarding additional factors that might influence treatment response, predictions for improving outcomes for non-responsive patients, and a discussion of how the proposed model might explain individual differences in vulnerability for mental health problems.}, } @article {pmid26050677, year = {2015}, author = {Mancini, F and Gangemi, A}, title = {The relevance of maintaining and worsening processes in psychopathology.}, journal = {The Behavioral and brain sciences}, volume = {38}, number = {}, pages = {e14}, doi = {10.1017/S0140525X14000375}, pmid = {26050677}, issn = {1469-1825}, mesh = {*Emotions ; Humans ; *Psychopathology ; }, abstract = {The states called "psychopathology" are very diverse, but Lane et al.'s single-process explanation does little to account for this diversity. Moreover, some other crucial phenomena of psychopathology do not fit this theory: the role of negative evaluations of conscious emotions, and the role of emotions without physiological correlates. And it does not consider the processes maintaining disorders.}, } @article {pmid26049738, year = {2015}, author = {McDonald, H and Charles, C and Elit, L and Gafni, A}, title = {The Silence in Hoch et al.'s Commentary about the Rationale for and Objective(s) of Canada's Separate HTA Process for Cancer Drugs: The Importance of Transparency and Accountability when Allocating Taxpayers' Dollars.}, journal = {PharmacoEconomics}, volume = {33}, number = {8}, pages = {883-886}, pmid = {26049738}, issn = {1179-2027}, mesh = {Antineoplastic Agents/economics/*therapeutic use ; Canada ; Disclosure ; Humans ; Neoplasms/*drug therapy/economics ; Resource Allocation ; Social Responsibility ; Taxes/economics ; Technology Assessment, Biomedical/*methods ; }, } @article {pmid26037464, year = {2015}, author = {Lovakov, AV and Agadullina, ER and Osin, EN}, title = {A hierarchical (multicomponent) model of in-group identification: examining in Russian samples.}, journal = {The Spanish journal of psychology}, volume = {18}, number = {}, pages = {E32}, doi = {10.1017/sjp.2015.37}, pmid = {26037464}, issn = {1988-2904}, mesh = {Adolescent ; Adult ; Female ; *Group Processes ; Humans ; Male ; Middle Aged ; *Models, Psychological ; Reproducibility of Results ; Russia ; *Social Identification ; Young Adult ; }, abstract = {The aim of this study was to examine the validity and reliability of Leach et al.'s (2008) model of in-group identification in two studies using Russian samples (overall N = 621). In Study 1, a series of multi-group confirmatory factor analysis revealed that the hierarchical model of in-group identification, which included two second-order factors, self-definition (individual self-stereotyping, and in-group homogeneity) and self-investment (satisfaction, solidarity, and centrality), fitted the data well for all four group identities (ethnic, religious, university, and gender) (CFI > .93, TLI > .92, RMSEA < .06, SRMR < .06) and demonstrated a better fit, compared to the alternative models. In Study 2, the construct validity and reliability of the Russian version of the in-group identification measure was examined. Results show that these measures have adequate psychometric properties. In short, our results show that Leach et al.'s model is reproduced in Russian culture. The Russian version of this measure can be recommended for use in future in-group research in Russian-speaking samples.}, } @article {pmid26033814, year = {2015}, author = {Vaughn, DJ}, title = {Reply to J. Beyer, T. Tandstad et al, S. Gillessen et al, J. Oldenburg et al, and L.C. Pagliaro et al.}, journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology}, volume = {33}, number = {20}, pages = {2324-2325}, doi = {10.1200/JCO.2015.61.4834}, pmid = {26033814}, issn = {1527-7755}, mesh = {Humans ; Male ; *Neoplasm Recurrence, Local ; Neoplasms, Germ Cell and Embryonal/*surgery/*therapy ; *Orchiectomy ; Seminoma/*diagnosis/*pathology ; Testicular Neoplasms/*diagnosis/*pathology/*surgery/*therapy ; }, } @article {pmid26032950, year = {2015}, author = {Carlisle, JB and Dexter, F and Pandit, JJ and Shafer, SL and Yentis, SM}, title = {Calculating the probability of random sampling for continuous variables in submitted or published randomised controlled trials.}, journal = {Anaesthesia}, volume = {70}, number = {7}, pages = {848-858}, doi = {10.1111/anae.13126}, pmid = {26032950}, issn = {1365-2044}, mesh = {Analysis of Variance ; Humans ; Monte Carlo Method ; *Probability ; *Random Allocation ; *Randomized Controlled Trials as Topic ; }, abstract = {In a previous paper, one of the authors (JBC) used a chi-squared method to analyse the means (SD) of baseline variables, such as height or weight, from randomised controlled trials by Fujii et al., concluding that the probabilities that the reported distributions arose by chance were infinitesimally small. Subsequent testing of that chi-squared method, using simulation, suggested that the method was incorrect. This paper corrects the chi-squared method and tests its performance and the performance of Monte Carlo simulations and ANOVA to analyse the probability of random sampling. The corrected chi-squared method and ANOVA method became inaccurate when applied to means that were reported imprecisely. Monte Carlo simulations confirmed that baseline data from 158 randomised controlled trials by Fujii et al. were different to those from 329 trials published by other authors and that the distribution of Fujii et al.'s data were different to the expected distribution, both p < 10(-16) . The number of Fujii randomised controlled trials with unlikely distributions was less with Monte Carlo simulation than with the 2012 chi-squared method: 102 vs 117 trials with p < 0.05; 60 vs 86 for p < 0.01; 30 vs 56 for p < 0.001; and 12 vs 24 for p < 0.00001, respectively. The Monte Carlo analysis nevertheless confirmed the original conclusion that the distribution of the data presented by Fujii et al. was extremely unlikely to have arisen from observed data. The Monte Carlo analysis may be an appropriate screening tool to check for non-random (i.e. unreliable) data in randomised controlled trials submitted to journals.}, } @article {pmid26032912, year = {2015}, author = {Morimont, P and Pironet, A and Desaive, T and Chase, G and Lambermont, B}, title = {Re: Chung et al.'s Letter to the Editor in response to: Early detection of abnormal left ventricular relaxation in acute myocardial ischemia with a quadratic model. Med Eng Phys 2014;36(September (9)):1101-5 by Morimont et al.}, journal = {Medical engineering & physics}, volume = {37}, number = {8}, pages = {827}, doi = {10.1016/j.medengphy.2015.05.001}, pmid = {26032912}, issn = {1873-4030}, mesh = {Animals ; *Models, Cardiovascular ; Myocardial Ischemia/*physiopathology ; Ventricular Function, Left/*physiology ; }, } @article {pmid26026849, year = {2015}, author = {McMullen, H and Griffiths, C and Leber, W and Greenhalgh, T}, title = {Explaining high and low performers in complex intervention trials: a new model based on diffusion of innovations theory.}, journal = {Trials}, volume = {16}, number = {}, pages = {242}, pmid = {26026849}, issn = {1745-6215}, support = {DRF-2012-05-454/DH_/Department of Health/United Kingdom ; }, mesh = {Attitude of Health Personnel ; *CD4 Lymphocyte Count ; Clinical Competence ; Clinical Protocols ; Delivery of Health Care/*organization & administration ; Diffusion of Innovation ; General Practice/*organization & administration ; General Practitioners/organization & administration ; HIV Infections/*diagnosis/epidemiology/immunology/virology ; Health Services Research ; Humans ; London/epidemiology ; *Models, Organizational ; Patient Care Team/organization & administration ; *Patient Selection ; Point-of-Care Testing/*organization & administration ; Predictive Value of Tests ; Prevalence ; Professional-Patient Relations ; Retrospective Studies ; }, abstract = {BACKGROUND: Complex intervention trials may require health care organisations to implement new service models. In a recent cluster randomised controlled trial, some participating organisations achieved high recruitment, whereas others found it difficult to assimilate the intervention and were low recruiters. We sought to explain this variation and develop a model to inform organisational participation in future complex intervention trials.

METHODS: The trial included 40 general practices in a London borough with high HIV prevalence. The intervention was offering a rapid HIV test as part of the New Patient Health Check. The primary outcome was mean CD4 cell count at diagnosis. The process evaluation consisted of several hundred hours of ethnographic observation, 21 semi-structured interviews and analysis of routine documents (e.g., patient leaflets, clinical protocols) and trial documents (e.g., inclusion criteria, recruitment statistics). Qualitative data were analysed thematically using--and, where necessary, extending--Greenhalgh et al.'s model of diffusion of innovations. Narrative synthesis was used to prepare case studies of four practices representing maximum variety in clinicians' interest in HIV (assessed by level of serological testing prior to the trial) and performance in the trial (high vs. low recruiters).

RESULTS: High-recruiting practices were, in general though not invariably, also innovative practices. They were characterised by strong leadership, good managerial relations, readiness for change, a culture of staff training and available staff time ('slack resources'). Their front-line staff believed that patients might benefit from the rapid HIV test ('relative advantage'), were emotionally comfortable administering it ('compatibility'), skilled in performing it ('task issues') and made creative adaptations to embed the test in local working practices ('reinvention'). Early experience of a positive HIV test ('observability') appeared to reinforce staff commitment to recruiting more participants. Low-performing practices typically had less good managerial relations, significant resource constraints, staff discomfort with the test and no positive results early in the trial.

CONCLUSIONS: An adaptation of the diffusion of innovations model was an effective analytical tool for retrospectively explaining high and low-performing practices in a complex intervention research trial. Whether the model will work prospectively to predict performance (and hence shape the design of future trials) is unknown.

TRIAL REGISTRATION: ISRCTN Registry number: ISRCTN63473710. Date assigned: 22 April 2010.}, } @article {pmid26015093, year = {2015}, author = {Shapiro, JH and Venkatraman, D and Wong, FN}, title = {Classical imaging with undetected photons.}, journal = {Scientific reports}, volume = {5}, number = {}, pages = {10329}, pmid = {26015093}, issn = {2045-2322}, abstract = {Barreto Lemos et al. [Nature 512, 409-412 (2014)] reported an experiment in which a non-degenerate parametric downconverter and a non-degenerate optical parametric amplifier--used as a wavelength-converting phase conjugator--were employed to image object transparencies in a manner akin to ghost imaging. Their experiment, however, relied on single-photon detection, rather than the photon-coincidence measurements employed in ghost imaging with a parametric downconverter source. More importantly, their system formed images despite the photons that passed through the object never being detected. Barreto Lemos et al. interpreted their experiment as a quantum imager, as assuredly it is, owing to its downconverter's emitting entangled signal and idler beams. We show, however, that virtually all the features of their setup can be realized in a quantum-mimetic fashion using classical-state light, specifically a pair of bright pseudothermal beams possessing a phase-sensitive cross correlation. Owing to its much higher signal-to-noise ratio, our bright-source classical imager could greatly reduce image-acquisition time compared to that of Barreto Lemos et al.'s quantum system, while retaining the latter's ability to image with undetected photons.}, } @article {pmid26014610, year = {2015}, author = {Ciampi, E and Tur, C and Montalban, X}, title = {Commentary on Pique et al.'s paper entitled: Peripheral late reactivation of a previously typical monofocal Balo's concentric sclerosis lesion.}, journal = {Multiple sclerosis (Houndmills, Basingstoke, England)}, volume = {21}, number = {8}, pages = {1084-1086}, doi = {10.1177/1352458515586090}, pmid = {26014610}, issn = {1477-0970}, mesh = {Diffuse Cerebral Sclerosis of Schilder/*pathology ; Female ; Humans ; }, } @article {pmid26013430, year = {2016}, author = {Son, KM and Lee, SM and Lee, GW and Ahn, MH and Son, JH}, title = {The Impact of Lumbosacral Transitional Vertebrae on Therapeutic Outcomes of Transforaminal Epidural Injection in Patients with Lumbar Disc Herniation.}, journal = {Pain practice : the official journal of World Institute of Pain}, volume = {16}, number = {6}, pages = {688-695}, doi = {10.1111/papr.12315}, pmid = {26013430}, issn = {1533-2500}, mesh = {Adult ; Aged ; Female ; Fluoroscopy ; Follow-Up Studies ; Humans ; Injections, Epidural/*methods ; Intervertebral Disc Displacement/diagnostic imaging/*drug therapy/pathology ; Lumbar Vertebrae/*abnormalities/diagnostic imaging/pathology ; Lumbosacral Region/*abnormalities/diagnostic imaging/pathology ; Male ; Middle Aged ; Pain Management/methods ; Pain Measurement ; Prospective Studies ; Treatment Outcome ; }, abstract = {BACKGROUND: Although some studies have evaluated the clinical impact of lumbosacral transitional vertebrae (LSTV), few have attempted to determine an effective conservative treatment method for lumbar disc herniation (LDH) presenting concurrently with LSTV.

METHODS: We prospectively enrolled 291 consecutive patients who were followed-up for at least one year after transforaminal epidural injection (TFEI) for LDH. We confirmed the presence of LSTV with Paik et al.'s method, the Castellvi classification, and the Southworth and Bersack method. Clinical outcomes were evaluated with a visual analogue scale (VAS) for pain intensity and the Oswestry Disability Index (ODI) for functional status.

RESULTS: Of the 291 patients, 47 (16.2%) had LSTV, including 33 with sacralization and 14 with lumbarization, while 244 (83.8%) did not have LSTV. Patients in both groups improved significantly after TFEI in terms of the VAS (P < 0.001) and ODI (P < 0.001) scores. However, LDH patients with LSTV had a worse clinical outcome after six months of TFEI than did those without LSTV, with a significant difference between groups for both the VAS (P < 0.01) and ODI (P = 0.01) scores. LDH patients with sacralization had worse post-treatment clinical outcomes than LDH patients with lumbarization (P < 0.001) or LDH patients without LSTV (P < 0.001).

CONCLUSIONS: Sacralization can reduce the improvement after TFEI among LDH patients, while lumbarization appears to have no direct effect on TFEI outcomes. The presence of sacralization should be identified before TFEI, and if present, patients should be informed that the outcomes of TFEI may not be as good as they would be if sacralization was not present.}, } @article {pmid26012872, year = {2015}, author = {Garzón-Orduña, IJ and Silva-Brandão, KL and Willmott, KR and Freitas, AV and Brower, AV}, title = {Incompatible Ages for Clearwing Butterflies Based on Alternative Secondary Calibrations.}, journal = {Systematic biology}, volume = {64}, number = {5}, pages = {752-767}, doi = {10.1093/sysbio/syv032}, pmid = {26012872}, issn = {1076-836X}, mesh = {Animals ; Butterflies/*classification ; Classification/*methods ; Fossils ; *Phylogeny ; Solanaceae/classification ; Time ; }, abstract = {The recent publication of a time-tree for the plant family Solanaceae (nightshades) provides the opportunity to use independent calibrations to test divergence times previously inferred for the diverse Neotropical butterfly tribe Ithomiini. Ithomiini includes clades that are obligate herbivores of Solanaceae, with some genera feeding on only one genus. We used 8 calibrations extracted from the plant tree in a new relaxed molecular-clock analysis to produce an alternative temporal framework for the diversification of ithomiines. We compared the resulting age estimates to: (i) a time-tree obtained using 7 secondary calibrations from the Nymphalidae tree of Wahlberg et al. (2009), and (ii) Wahlberg et al.'s (2009) original age estimates for the same clades. We found that Bayesian clock estimates were rather sensitive to a variety of analytical parameters, including taxon sampling. Regardless of this sensitivity however, ithomiine divergence times calibrated with the ages of nightshades were always on average half the age of previous estimates. Younger dates for ithomiine clades appear to fit better with factors long suggested to have promoted diversification of the group such as the uplifting of the Andes, in the case of montane genera. Alternatively, if ithomiines are as old as previous estimates suggest, the recent ages inferred for the diversification of Solanaceae seem likely to be seriously underestimated. Our study exemplifies the difficulty of testing hypotheses of divergence times and of choosing between alternative dating scenarios, and shows that age estimates based on seemingly plausible calibrations may be grossly incongruent.}, } @article {pmid26011571, year = {2016}, author = {Ishikawa, T and Abe, S and Kojima, Y and Kojima, S and Yoshida, T}, title = {Discrepant diagnostic results using two genotyping methods in a chronic hepatitis C patient in serogroup 1.}, journal = {Hepatology research : the official journal of the Japan Society of Hepatology}, volume = {46}, number = {4}, pages = {354-356}, doi = {10.1111/hepr.12536}, pmid = {26011571}, issn = {1386-6346}, abstract = {We present the case of a chronic hepatitis C (CHC) patient who was originally diagnosed with genotype 2a on serogroup 1 CHC genotype testing, but who was subsequently confirmed to have genotype 1b when using the hepatitis C virus (HCV) monitor genotype assay. The genotype 2a diagnosis was attributed to the fact that the type 2a-specific primer used in Okamoto et al.'s method (HCV genotype primer kit) has relatively high homology, which caused the amplification reaction to proceed, rendering a HCV RNA genotype test result of 2a. Genotype testing is important in determining whether a patient is indicated for concomitant dual oral therapy; however, the potential for different diagnoses such as described in this report highlights the importance of serogroup confirmation.}, } @article {pmid26007740, year = {2015}, author = {Peinado, A and Munilla, J and Fúster-Sabater, A}, title = {Revision of J3Gen and Validity of the Attacks by Peinado et al.}, journal = {Sensors (Basel, Switzerland)}, volume = {15}, number = {5}, pages = {11988-11992}, pmid = {26007740}, issn = {1424-8220}, abstract = {This letter is the reply to: Remarks on Peinado et al.'s Analysis of J3Gen by J. Garcia-Alfaro, J. Herrera-Joancomartí and J. Melià-Seguí published in Sensors 2015, 15, 6217-6220. Peinado et al. cryptanalyzed the pseudorandom number generator proposed by Melià-Seguí et al., describing two possible attacks. Later, Garcia-Alfaro claimed that one of this attack did not hold in practice because the assumptions made by Peinado et al. were not correct. This letter reviews those remarks, showing that J3Gen is anyway flawed and that, without further information, the interpretation made by Peinado et al. seems to be correct.}, } @article {pmid26000940, year = {2016}, author = {Ruiz-García, M and Vásquez, C and Sandoval, S and Kaston, F and Luengas-Villamil, K and Shostell, JM}, title = {Phylogeography and spatial structure of the lowland tapir (Tapirus terrestris, Perissodactyla: Tapiridae) in South America.}, journal = {Mitochondrial DNA. Part A, DNA mapping, sequencing, and analysis}, volume = {27}, number = {4}, pages = {2334-2342}, doi = {10.3109/19401736.2015.1022766}, pmid = {26000940}, issn = {2470-1408}, mesh = {Animals ; Evolution, Molecular ; Genes, Mitochondrial ; Genetic Heterogeneity ; *Genetic Variation ; Genetics, Population ; Geography ; Perissodactyla/*classification/*genetics ; *Phylogeny ; *Phylogeography ; South America ; }, abstract = {We sequenced the mitochondrial cytochrome b gene of 141 lowland tapirs (Tapirus terrestris) - representing the largest geographical distribution sample of this species studied across of South America to date. We compare our new data regard to two previous works on population structure and molecular systematics of T. terrestris. Our data agree with the Thoisy et al.'s work in (1) the Northern Western Amazon basin was the area with the highest gene diversity levels in T. terrestris, being probably the area of initial diversification; (2) there was no clear association between haplogroups and specific geographical areas; (3) there were clear population decreases during the last glacial maximum for the different haplogroups detected, followed by population expansions during the Holocene; and (4) our temporal splits among different T. terrestris haplogroups coincided with the first molecular clock approach carried out by these authors (fossil calibration). Nevertheless, our study disagreed regard to other aspects of the Thoisy et al.'s claims: (1) meanwhile, they detected four relevant clades in their data, we put forward six different relevant clades; (2) the Amazon River was not a strong barrier for haplotype dispersion in T. terrestris; and (3) we found reciprocal monophyly between T. terrestris and T. pinchaque. Additionally, we sequenced 42 individuals (T. terrestris, T. pinchaque, T. bairdii, and the alleged "new species", T. kabomani) for three concatenated mitochondrial genes (Cyt-b, COI, and COII) agreeing quite well with the view of Voss et al., and against of the claims of Cozzuol et al. Tapirus kabomani should be not considered as a full species with the results obtained throughout the mitochondrial sequences.}, } @article {pmid25996884, year = {2015}, author = {O'Donahoo, FJ and Ross, KE}, title = {Principles Relevant to Health Research among Indigenous Communities.}, journal = {International journal of environmental research and public health}, volume = {12}, number = {5}, pages = {5304-5309}, pmid = {25996884}, issn = {1660-4601}, mesh = {Community-Based Participatory Research/*methods ; Cultural Characteristics ; *Cultural Competency ; *Health Services, Indigenous ; Humans ; Narration ; Northern Territory ; }, abstract = {Research within Indigenous communities has been criticised for lacking community engagement, for being exploitative, and for poorly explaining the processes of research. To address these concerns, and to ensure 'best practice', Jamieson, et al. (2012) recently published a summary of principles outlined by the NHMRC (2003) in "one short, accessible document". Here we expand on Jamieson et al.'s paper, which while commendable, lacks emphasis on the contribution that communities themselves can make to the research process and how culturally appropriate engagement, can allow this contribution to be assured, specifically with respect to engagement with remote communities. Engagement started before the research proposal is put forward, and continued after the research is completed, has integrity. We emphasise the value of narratives, of understanding cultural and customary behaviours and leadership, the importance of cultural legitimacy, and of the need for time, not just to allow for delays, but to ensure genuine participatory engagement from all members of the community. We also challenge researchers to consider the outcomes of their research, on the basis that increasing clinical evidence does not always result in better outcomes for the community involved.}, } @article {pmid25978418, year = {2015}, author = {Hamm, JM and Perry, RP and Chipperfield, JG and Stewart, TL and Heckhausen, J}, title = {Motivation-focused thinking: Buffering against stress-related physical symptoms and depressive symptomology.}, journal = {Psychology & health}, volume = {30}, number = {11}, pages = {1326-1345}, doi = {10.1080/08870446.2015.1050394}, pmid = {25978418}, issn = {1476-8321}, mesh = {Adaptation, Psychological ; Adolescent ; Depression/*prevention & control/psychology ; Female ; Humans ; Male ; *Motivation ; Protective Factors ; Schools ; Stress, Psychological/complications/*prevention & control/psychology ; *Thinking ; Universities ; Young Adult ; }, abstract = {Developmental transitions are experienced throughout the life course and necessitate adapting to consequential and unpredictable changes that can undermine health. Our six-month study (n = 239) explored whether selective secondary control striving (motivation-focused thinking) protects against the elevated levels of stress and depressive symptoms increasingly common to young adults navigating the challenging school-to-university transition. Path analyses supplemented with tests of moderated mediation revealed that, for young adults who face challenging obstacles to goal attainment, selective secondary control indirectly reduced long-term stress-related physical and depressive symptoms through selective primary control and previously unexamined measures of discrete emotions. Results advance the existing literature by demonstrating that (a) selective secondary control has health benefits for vulnerable young adults and (b) these benefits are largely a consequence of the process variables proposed in Heckhausen et al.'s (2010) theory.}, } @article {pmid25978373, year = {2015}, author = {Lu, Y and Li, L and Yang, X and Yang, Y}, title = {Robust biometrics based authentication and key agreement scheme for multi-server environments using smart cards.}, journal = {PloS one}, volume = {10}, number = {5}, pages = {e0126323}, pmid = {25978373}, issn = {1932-6203}, mesh = {*Biometry ; Computer Security/instrumentation ; *Health Smart Cards ; Humans ; }, abstract = {Biometrics authenticated schemes using smart cards have attracted much attention in multi-server environments. Several schemes of this type where proposed in the past. However, many of them were found to have some design flaws. This paper concentrates on the security weaknesses of the three-factor authentication scheme by Mishra et al. After careful analysis, we find their scheme does not really resist replay attack while failing to provide an efficient password change phase. We further propose an improvement of Mishra et al.'s scheme with the purpose of preventing the security threats of their scheme. We demonstrate the proposed scheme is given to strong authentication against several attacks including attacks shown in the original scheme. In addition, we compare the performance and functionality with other multi-server authenticated key schemes.}, } @article {pmid25972822, year = {2015}, author = {Xenidou-Dervou, I and Gilmore, C and van der Schoot, M and van Lieshout, EC}, title = {The developmental onset of symbolic approximation: beyond nonsymbolic representations, the language of numbers matters.}, journal = {Frontiers in psychology}, volume = {6}, number = {}, pages = {487}, pmid = {25972822}, issn = {1664-1078}, abstract = {Symbolic (i.e., with Arabic numerals) approximate arithmetic with large numerosities is an important predictor of mathematics. It was previously evidenced to onset before formal schooling at the kindergarten age (Gilmore et al., 2007) and was assumed to map onto pre-existing nonsymbolic (i.e., abstract magnitudes) representations. With a longitudinal study (Experiment 1), we show, for the first time, that nonsymbolic and symbolic arithmetic demonstrate different developmental trajectories. In contrast to Gilmore et al.'s (2007) findings, Experiment 1 showed that symbolic arithmetic onsets in grade 1, with the start of formal schooling, not earlier. Gilmore et al. (2007) had examined English-speaking children, whereas we assessed a large Dutch-speaking sample. The Dutch language for numbers can be cognitively more demanding, for example, due to the inversion property in numbers above 20. Thus, for instance, the number 48 is named in Dutch "achtenveertig" (eight and forty) instead of "forty eight." To examine the effect of the language of numbers, we conducted a cross-cultural study with English- and Dutch-speaking children that had similar SES and math achievement skills (Experiment 2). Results demonstrated that Dutch-speaking kindergarteners lagged behind English-speaking children in symbolic arithmetic, not nonsymbolic and demonstrated a working memory overload in symbolic arithmetic, not nonsymbolic. Also, we show for the first time that the ability to name two-digit numbers highly correlates with symbolic approximate arithmetic not nonsymbolic. Our experiments empirically demonstrate that the symbolic number system is modulated more by development and education than the nonsymbolic system. Also, in contrast to the nonsymbolic system, the symbolic system is modulated by language.}, } @article {pmid25959320, year = {2015}, author = {Kolus, A and Imbeau, D and Dubé, PA and Dubeau, D}, title = {Adaptive neuro-fuzzy inference systems with k-fold cross-validation for energy expenditure predictions based on heart rate.}, journal = {Applied ergonomics}, volume = {50}, number = {}, pages = {68-78}, doi = {10.1016/j.apergo.2015.03.001}, pmid = {25959320}, issn = {1872-9126}, mesh = {Adult ; Energy Metabolism/*physiology ; Fuzzy Logic ; Heart Rate/*physiology ; Humans ; Male ; Middle Aged ; Motor Activity/physiology ; Neural Networks, Computer ; Oxygen Consumption/physiology ; Young Adult ; }, abstract = {This paper presents a new model based on adaptive neuro-fuzzy inference systems (ANFIS) to predict oxygen consumption (V˙O2) from easily measured variables. The ANFIS prediction model consists of three ANFIS modules for estimating the Flex-HR parameters. Each module was developed based on clustering a training set of data samples relevant to that module and then the ANFIS prediction model was tested against a validation data set. Fifty-eight participants performed the Meyer and Flenghi step-test, during which heart rate (HR) and V˙O2 were measured. Results indicated no significant difference between observed and estimated Flex-HR parameters and between measured and estimated V˙O2 in the overall HR range, and separately in different HR ranges. The ANFIS prediction model (MAE = 3 ml kg(-1) min(-1)) demonstrated better performance than Rennie et al.'s (MAE = 7 ml kg(-1) min(-1)) and Keytel et al.'s (MAE = 6 ml kg(-1) min(-1)) models, and comparable performance with the standard Flex-HR method (MAE = 2.3 ml kg(-1) min(-1)) throughout the HR range. The ANFIS model thus provides practitioners with a practical, cost- and time-efficient method for V˙O2 estimation without the need for individual calibration.}, } @article {pmid25956951, year = {2015}, author = {Wherley, C and Veach, PM and Martyr, MA and LeRoy, BS}, title = {Form Follows Function: A Model for Clinical Supervision of Genetic Counseling Students.}, journal = {Journal of genetic counseling}, volume = {24}, number = {5}, pages = {702-716}, pmid = {25956951}, issn = {1573-3599}, mesh = {*Clinical Competence ; Counseling ; Genetic Counseling/*organization & administration ; Humans ; Interprofessional Relations ; *Models, Educational ; *Students, Medical ; }, abstract = {Supervision plays a vital role in genetic counselor training, yet models describing genetic counseling supervision processes and outcomes are lacking. This paper describes a proposed supervision model intended to provide a framework to promote comprehensive and consistent clinical supervision training for genetic counseling students. Based on the principle "form follows function," the model reflects and reinforces McCarthy Veach et al.'s empirically derived model of genetic counseling practice - the "Reciprocal Engagement Model" (REM). The REM consists of mutually interactive educational, relational, and psychosocial components. The Reciprocal Engagement Model of Supervision (REM-S) has similar components and corresponding tenets, goals, and outcomes. The 5 REM-S tenets are: Learning and applying genetic information are key; Relationship is integral to genetic counseling supervision; Student autonomy must be supported; Students are capable; and Student emotions matter. The REM-S outcomes are: Student understands and applies information to independently provide effective services, develop professionally, and engage in self-reflective practice. The 16 REM-S goals are informed by the REM of genetic counseling practice and supported by prior literature. A review of models in medicine and psychology confirms the REM-S contains supervision elements common in healthcare fields, while remaining unique to genetic counseling. The REM-S shows promise for enhancing genetic counselor supervision training and practice and for promoting research on clinical supervision. The REM-S is presented in detail along with specific examples and training and research suggestions.}, } @article {pmid25949973, year = {2015}, author = {John, B}, title = {Sleep-patterns, sleep hygiene behaviors and parental monitoring among Bahrain-based Indian adolescents.}, journal = {Journal of family medicine and primary care}, volume = {4}, number = {2}, pages = {232-237}, pmid = {25949973}, issn = {2249-4863}, abstract = {INTRODUCTION: Sleep plays an important role in adolescent's health and undergoes substantial changes with puberty and physical maturation with a preference for later bed times. Evidence shows that many adolescents are not obtaining the required amounts of sleep which is 9.25 h, due to inadequate sleep practices, academic and societal demands. This study aims at describing the (1) sleep patterns of adolescents on school days and weekends, (2) sleep hygiene practices and the extent of parental monitoring and (3) gender and grade level differences in sleep duration and sleep hygiene practices among Indian adolescents in Bahrain.

MATERIALS AND METHODS: Study used a descriptive correlational design. A total of 145 adolescents from 11 to 17 years from grade 6 to 12 were selected using convenience sampling. Data was collected from November 2012 to March 2013. A structured questionnaire for sleep patterns and Mastin et al.'s Sleep Hygiene Index for assessing sleep hygiene practices were used.

RESULTS: The adolescents' total sleep duration was 7.07 ± 1.13 hours. A highly significant difference in sleep duration on school days and weekends between adolescents of various grade levels (P < 0.001 and 0.001, respectively) and between parental monitoring at the time of getting up on school days and sleep duration (P value 0.026 at 0.05 level of significance) was found. Gender was not significant with the sleep duration, and also with Sleep Hygiene Index scores.

CONCLUSION: The results suggest that there is a high prevalence of insufficient sleep and irregular bed-time schedule among Indian adolescents in Bahrain. Interventions directed toward improving sleep and promoting good sleep hygiene strategies are required to improve the physical and emotional health of adolescents.}, } @article {pmid25949798, year = {2015}, author = {Assis-Hassid, S and Reychav, I and Heart, T and Pliskin, JS and Reis, S}, title = {Enhancing patient-doctor-computer communication in primary care: towards measurement construction.}, journal = {Israel journal of health policy research}, volume = {4}, number = {}, pages = {4}, pmid = {25949798}, issn = {2045-4015}, abstract = {OBJECTIVE: The traditional dyadic dynamics of the medical encounter has been altered into a triadic relationship by introducing the computer into the examination room. This study defines Patient-Doctor-Computer Communication (PDCC) as a new construct and provides an initial validation process of an instrument for assessing PDCC in the computerized exam room: the e-SEGUE.

MATERIAL AND METHODS: Based on the existing literature, a new construct, PDCC, is defined as the physician's ability to provide patient-centered care while using the computer during the medical encounter. This study elucidates 27 PDCC-related behaviors from the relevant literature and state of the art models of PDCC. These were embedded in the SEGUE communication assessment framework to form the e-SEGUE, a communication skills assessment tool that integrates computer-related communication skills. Based on Mackenzie et al.'s methodological approach of measurement construction, we conducted a two-phased content validity analysis by a general and expert panels of the PDCC behaviors represented in the e-SEGUE. This study was carried out in an environment where EMR use is universal and fully integrated in the physicians' workflow.

RESULTS: The panels consisted of medical students, residents, primary care physicians, healthcare leaders and faculty of medicine members, who rated and provided input regarding the 27 behaviors. Overall, results show high level of agreement with 23 PDCC-related behaviors.

CONCLUSION: The PDCC instrument developed in this study, the e-SEGUE, fared well in a rigorous, albeit initial, validation process has a unique potential for training and enhancing patient-doctor communication (PDC) in the computerized examination room pending further development.}, } @article {pmid25947360, year = {2015}, author = {Kazanas, SA and Altarriba, J}, title = {The survival advantage: Underlying mechanisms and extant limitations.}, journal = {Evolutionary psychology : an international journal of evolutionary approaches to psychology and behavior}, volume = {13}, number = {2}, pages = {360-396}, pmid = {25947360}, issn = {1474-7049}, mesh = {Humans ; Learning ; *Mental Recall ; *Problem Solving ; Psycholinguistics ; Set, Psychology ; Survival/*psychology ; }, abstract = {Recently, researchers have begun to investigate the function of memory in our evolutionary history. According to Nairne and colleagues (e.g., Nairne, Pandeirada, and Thompson, 2008; Nairne, Thompson, and Pandeirada, 2007), the best mnemonic strategy for learning lists of unrelated words may be one that addresses the same problems that our Pleistocene ancestors faced: fitness-relevant problems including securing food and water, as well as protecting themselves from predators. Survival processing has been shown to promote better recall and recognition memory than many well-known mnemonic strategies (e.g., pleasantness ratings, imagery, generation, etc.). However, the survival advantage does not extend to all types of stimuli and tasks. The current review presents research that has replicated Nairne et al.'s (2007) original findings, in addition to the research designs that fail to replicate the survival advantage. In other words, there are specific manipulations in which survival processing does not appear to benefit memory any more than other strategies. Potential mechanisms for the survival advantage are described, with an emphasis on those that are the most plausible. These proximate mechanisms outline the memory processes that may contribute to the advantage, although the ultimate mechanism may be the congruity between the survival scenario and Pleistocene problem-solving.}, } @article {pmid25947107, year = {2015}, author = {Tarescavage, AM and Ben-Porath, YS}, title = {A Response to Odland et al.'s Misleading, Alarmist Estimates of Risk for Overpathologizing when Interpreting the MMPI-2-RF.}, journal = {The Clinical neuropsychologist}, volume = {29}, number = {2}, pages = {183-196}, doi = {10.1080/13854046.2015.1040843}, pmid = {25947107}, issn = {1744-4144}, mesh = {Adult ; *Data Interpretation, Statistical ; Humans ; *MMPI/standards ; Mental Disorders/*diagnosis/psychology ; Neuropsychological Tests ; }, abstract = {In a recently published article in this journal, Odland, Lammy, Perle, Martin, and Grote report Monte Carlo-simulated normative base rates of scale elevations on the Minnesota Multiphasic Personality Inventory-2-Restructured Form (MMPI-2-RF). Their primary conclusion--reflected in the title of their article--is that MMPI-2-RF interpretation is associated with "high risk of pathologizing healthy adults" when the 40 substantive scales of the test are simultaneously interpreted. In this paper, we describe how their conclusion follows from several faulty premises, three of which were already debunked in an earlier article and remain false despite counterarguments proposed by Odland and colleagues. We also address these authors' misinterpretation of their analyses and, furthermore, their premise that MMPI-2-RF interpretive guidelines are flawed because they "currently do not account for a basic statistical principle: Type I (or alpha) error inflation" (p. 1). This premise is irrelevant to psychological test interpretation and misaligned with neuropsychological testing literature cited in support of it. Consistent with suggestions by some of the authors they cite, we reiterate MMPI-2-RF interpretive guidelines designed to mitigate the impact of measurement error (not alpha error) by way of a scientific assessment approach that relies on integration of information derived from multiple sources.}, } @article {pmid25939816, year = {2015}, author = {Filler, G}, title = {A step forward towards accurately assessing glomerular filtration rate in newborns.}, journal = {Pediatric nephrology (Berlin, Germany)}, volume = {30}, number = {8}, pages = {1209-1212}, pmid = {25939816}, issn = {1432-198X}, mesh = {Cystatin C/*blood ; Female ; *Glomerular Filtration Rate ; Humans ; Infant, Small for Gestational Age/*blood ; Kidney/*diagnostic imaging ; Kidney Function Tests/*methods ; Male ; Ultrasonography ; }, abstract = {In this edition of Pediatric Nephrology, Milena Treiber and colleagues have published a study on cystatin C (CysC) concentrations in relation to renal volumetry in 50 small-for-gestational age (SGA) and 50 appropriate-for-gestational age (AGA) neonates, deriving a new formula for estimating neonatal glomerular filtration rate (GFR). The study builds on previous work which established that renal volumetry together with CysC blood levels is a superior method for establishing GFR in term and pre-term newborns [The Journal of Pediatrics (2014) 164:1026-1031.e2]. Treiber et al. use the expected difference between SGA and AGA renal volumes to document the superiority of their new formula, which is based on total renal volume, CysC and body surface area, but does not incorporate gold-standard inulin clearance. Treiber et al.'s study adds new knowledge to the field that will hopefully improve the safety of renally excreted critical dose drugs in the newborn period. This editorial discusses the strengths and limitations of the current study.}, } @article {pmid25939483, year = {2016}, author = {Booroff, M and Nelson, L and Potrac, P}, title = {A coach's political use of video-based feedback: a case study in elite-level academy soccer.}, journal = {Journal of sports sciences}, volume = {34}, number = {2}, pages = {116-124}, doi = {10.1080/02640414.2015.1039464}, pmid = {25939483}, issn = {1466-447X}, mesh = {*Formative Feedback ; Humans ; Interprofessional Relations ; Male ; *Politics ; Professionalism ; Soccer/*psychology ; *Task Performance and Analysis ; *Video Recording ; }, abstract = {This paper examines the video-based pedagogical practices of Terry (pseudonym), a head coach of a professional junior academy squad. Data were collected through 6 in-depth, semi-structured interviews and 10 field observations of Terry's video-based coaching in situ. Three embracing categories were generated from the data. These demonstrated that Terry's video-based coaching was far from apolitical. Rather, Terry strategically used performance analysis technologies to help fulfil various objectives and outcomes that he understood to be expected of him within the club environment. Kelchtermans' micropolitical perspective, Callero's work addressing role and Groom et al.'s grounded theory were primarily utilised to make sense of Terry's perceptions and actions. The findings point to the value of developing contextually grounded understandings of coaches' uses of video-based performance analysis technology. Doing so could better prepare coaches for this aspect of their coaching practice.}, } @article {pmid25939067, year = {2015}, author = {Nagoshi, N and Nakashima, H and Fehlings, MG}, title = {Riluzole as a neuroprotective drug for spinal cord injury: from bench to bedside.}, journal = {Molecules (Basel, Switzerland)}, volume = {20}, number = {5}, pages = {7775-7789}, pmid = {25939067}, issn = {1420-3049}, mesh = {Adult ; Amyotrophic Lateral Sclerosis/drug therapy ; Animals ; Clinical Trials as Topic ; Humans ; Neuroprotective Agents/pharmacology/*therapeutic use ; Rats ; Riluzole/pharmacology/*therapeutic use ; Sodium Channel Blockers/*therapeutic use ; Spinal Cord Injuries/*drug therapy ; Synaptic Transmission/*drug effects ; }, abstract = {Spinal cord injury (SCI) is a devastating event resulting in permanent loss of neurological function. To date, effective therapies for SCI have not been established. With recent progress in neurobiology, however, there is hope that drug administration could improve outcomes after SCI. Riluzole is a benzothiazole anticonvulsant with neuroprotective effects. It has been approved by the U.S. Food and Drug Administration as a safe and well-tolerated treatment for patients with amyotrophic lateral sclerosis. The mechanism of action of riluzole involves the inhibition of pathologic glutamatergic transmission in synapses of neurons via sodium channel blockade. There is convincing evidence that riluzole diminishes neurological tissue destruction and promotes functional recovery in animal SCI models. Based on these results, a phase I/IIa clinical trial with riluzole was conducted for patients with SCI between 2010 and 2011. This trial demonstrated significant improvement in neurological outcomes and showed it to be a safe drug with no serious adverse effects. Currently, an international, multi-center clinical trial (Riluzole in Acute Spinal Cord Injury Study: RISCIS) in phase II/III is in progress with riluzole for patients with SCI (clinicaltrials.gov, registration number NCT01597518). This article reviews the pharmacology and neuroprotective mechanisms of riluzole, and focuses on existing preclinical evidence, and emerging clinical data in the treatment of SCI.}, } @article {pmid25935135, year = {2015}, author = {Fontecave-Jallon, J and Thomas, SR}, title = {Implementation of a model of bodily fluids regulation.}, journal = {Acta biotheoretica}, volume = {63}, number = {3}, pages = {269-282}, pmid = {25935135}, issn = {1572-8358}, mesh = {Acidosis, Respiratory ; Alkalosis ; Blood Pressure/*physiology ; Body Fluids/*physiology ; Computer Simulation ; Hemoglobins/chemistry ; Humans ; Hypertension/physiopathology ; Kidney/metabolism/*physiology ; Microcomputers ; *Models, Biological ; Osmolar Concentration ; Programming Languages ; *Respiration ; }, abstract = {The classic model of blood pressure regulation by Guyton et al. (Annu Rev Physiol 34:13-46, 1972a; Ann Biomed Eng 1:254-281, 1972b) set a new standard for quantitative exploration of physiological function and led to important new insights, some of which still remain the focus of debate, such as whether the kidney plays the primary role in the genesis of hypertension (Montani et al. in Exp Physiol 24:41-54, 2009a; Exp Physiol 94:382-388, 2009b; Osborn et al. in Exp Physiol 94:389-396, 2009a; Exp Physiol 94:388-389, 2009b). Key to the success of this model was the fact that the authors made the computer code (in FORTRAN) freely available and eventually provided a convivial user interface for exploration of model behavior on early microcomputers (Montani et al. in Int J Bio-med Comput 24:41-54, 1989). Ikeda et al. (Ann Biomed Eng 7:135-166, 1979) developed an offshoot of the Guyton model targeting especially the regulation of body fluids and acid-base balance; their model provides extended renal and respiratory functions and would be a good basis for further extensions. In the interest of providing a simple, useable version of Ikeda et al.'s model and to facilitate further such extensions, we present a practical implementation of the model of Ikeda et al. (Ann Biomed Eng 7:135-166, 1979), using the ODE solver Berkeley Madonna.}, } @article {pmid25933988, year = {2015}, author = {McBride, DW and Klebe, D and Tang, J and Zhang, JH}, title = {Correcting for Brain Swelling's Effects on Infarct Volume Calculation After Middle Cerebral Artery Occlusion in Rats.}, journal = {Translational stroke research}, volume = {6}, number = {4}, pages = {323-338}, pmid = {25933988}, issn = {1868-601X}, support = {P01 NS082184/NS/NINDS NIH HHS/United States ; R01 NS043338/NS/NINDS NIH HHS/United States ; }, mesh = {*Algorithms ; Animals ; Brain/*pathology ; *Brain Edema/complications/etiology/pathology ; Disease Models, Animal ; Functional Laterality ; *Image Processing, Computer-Assisted ; Infarction, Middle Cerebral Artery/*complications/pathology ; Male ; Rats ; Rats, Sprague-Dawley ; Reperfusion ; Tetrazolium Salts/metabolism ; Time Factors ; }, abstract = {Evaluating infarct volume is the primary outcome for experimental ischemic stroke studies and is a major factor in determining translation of a drug into clinical trials. Numerous algorithms are available for evaluating this critical value, but a major limitation of current algorithms is that brain swelling is not appropriately considered. The model by Lin et al. is widely used, but overestimates swelling within the infarction, yielding infarct volumes which do not reflect the true infarct size. Herein, a new infarct volume algorithm is developed to minimize the effects of both peri-infarct and infarct core swelling on infarct volume measurement. 2,3,5-Triphenyl-2H-tetrazolium chloride-stained brain tissue of adult rats subjected to middle cerebral artery occlusion was used for infarct volume analysis. When both peri-infarct swelling and infarction core swelling are removed from infarct volume calculations, such as accomplished by our algorithm, larger infarct volumes are estimated than those of Lin et al.'s algorithm. Furthermore, the infarct volume difference between the two algorithms is the greatest for small infarcts (<10% of brain volume) when peri-infarct swelling is the greatest. Finally, using data from four published studies, our algorithm is compared to Lin et al.'s algorithm. Our algorithm offers a more reliable estimation of the infarct volume after ischemic brain injury, and thus may provide the foundation for comparing infarct volumes between experimental studies and standardizing infarct volume quantification to aid in the selection of the best candidates for clinical trials.}, } @article {pmid25931380, year = {2015}, author = {Malone, JC and Dayton, CJ}, title = {What is the container/contained when there are ghosts in the nursery?: Joining Bion and Fraiberg in dyadic interventions with mother and infant.}, journal = {Infant mental health journal}, volume = {36}, number = {3}, pages = {262-274}, doi = {10.1002/imhj.21509}, pmid = {25931380}, issn = {1097-0355}, mesh = {Child Abuse/*psychology/*therapy ; Child Development ; Humans ; Infant ; Mother-Child Relations/*psychology ; Mothers/*psychology ; Object Attachment ; Psychotherapy/*methods ; }, abstract = {"Ghosts in the nursery." "Visitors from the unremembered past." Fraiberg, Adelson, and Shapiro's (1975) words convey the relational "intruders" that they perceived while working with mothers and infants. A mother's unresolved past is a driving force within the treatment of mother-infant dyads. Working with these families, the therapist strives to process and metabolize the distress of the dyad while enabling the mother to contain the infant more fully. This article proposes that Fraiberg et al.'s metaphor may be newly elaborated utilizing Bion's (1962) original theoretical conceptualization of the "container and contained." He posited that an infant projects distressing affective states upon the mother, who contains the experience, transforms the feelings, and then enables the infant to reintroject a more tolerable experience. This lays the foundation for the relational experience of being known by another and facilitates the infant's development of self-knowledge and emotional regulation. We utilize Fraiberg et al.'s original case material to identify ways in which ghosts in the nursery disrupt the processes of the container and contained. Bion's ideas may help enrich our understanding of how the therapeutic relationship enables cycles of containment, transitioning the material "ghosts" from being contained by the infant to being contained by the therapist, and to ultimately being transformed so that the mother can reattribute them to the past.}, } @article {pmid25913813, year = {2015}, author = {Oates, K}, title = {Some reflections from the past and some ideas for the future: The 2014 Kempe Oration.}, journal = {Child abuse & neglect}, volume = {43}, number = {}, pages = {1-7}, doi = {10.1016/j.chiabu.2015.03.017}, pmid = {25913813}, issn = {1873-7757}, mesh = {Child ; Child Abuse/*history ; Child Welfare ; History, 20th Century ; History, 21st Century ; Humans ; Physical Abuse/*history ; Public Health ; Risk Factors ; }, abstract = {Although the physical features of child abuse had been described before 1962, it was Henry Kempe et al.'s article "The Battered Child Syndrome" that is regarded as the beginning of widespread awareness and acceptance of this previously hidden problem. It was another 15 years before child sex abuse started to receive similar widespread recognition. As awareness of child abuse increased, its size became apparent. Funds were poured into child abuse detection and Child Protective Services, although evaluation of the effects of these initiatives did not proceed at the same pace. In those early days, child abuse was conceived in pathological terms, as a problem found only in particular types of families. We now know it is more helpful to use an ecological model and in so doing to consider societal, community, family, and individual factors in interaction. As for the future, we have much to learn from areas such as: public health, where a preventive approach is emphasized; the interaction between researchers and front line workers and insights from high reliability organizations that have been so beneficial to the patient safety movement. In particular, new research about the way our environment and our experiences can influence the way our genes function may reveal new opportunities for prevention, early intervention, and treatment.}, } @article {pmid25912427, year = {2015}, author = {Chaudhry, SA and Naqvi, H and Shon, T and Sher, M and Farash, MS}, title = {Cryptanalysis and improvement of an improved two factor authentication protocol for telecare medical information systems.}, journal = {Journal of medical systems}, volume = {39}, number = {6}, pages = {66}, pmid = {25912427}, issn = {1573-689X}, mesh = {Communication ; Computer Security/*standards ; Confidentiality/*standards ; Health Information Systems/organization & administration/*standards ; Humans ; Patient Access to Records/*standards ; Professional-Patient Relations ; Telemedicine/methods/organization & administration/*standards ; User-Computer Interface ; }, abstract = {Telecare medical information systems (TMIS) provides rapid and convenient health care services remotely. Efficient authentication is a prerequisite to guarantee the security and privacy of patients in TMIS. Authentication is used to verify the legality of the patients and TMIS server during remote access. Very recently Islam et al. (J. Med. Syst. 38(10):135, 2014) proposed a two factor authentication protocol for TMIS using elliptic curve cryptography (ECC) to improve Xu et al.'s (J. Med. Syst. 38(1):9994, 2014) protocol. They claimed their improved protocol to be efficient and provides all security requirements. However our analysis reveals that Islam et al.'s protocol suffers from user impersonation and server impersonation attacks. Furthermore we proposed an enhanced protocol. The proposed protocol while delivering all the virtues of Islam et al.'s protocol resists all known attacks.}, } @article {pmid25907148, year = {2015}, author = {Smuts, B and Bauer, E and Ward, C}, title = {Rollovers during play: Complementary perspectives.}, journal = {Behavioural processes}, volume = {116}, number = {}, pages = {50-52}, doi = {10.1016/j.beproc.2015.04.006}, pmid = {25907148}, issn = {1872-8308}, mesh = {Animals ; Behavior, Animal/*physiology ; *Play and Playthings ; Posture/*physiology ; *Social Behavior ; }, abstract = {In this commentary, we compare and contrast Norman et al.s' findings on rollovers during dog play (Norman et al., 2015; the "target article") with our work on dog play fighting (Bauer and Smuts, 2007; Ward et al., 2008). We first review our major findings and then correct some errors in the target article's descriptions of our work. We then further explore the concept of "defensive" rollovers proposed in the target article. We conclude that a combination of the target article's approach and ours should inform future investigations of dog rollovers.}, } @article {pmid25905730, year = {2016}, author = {Kalpakci, A and Vanwoerden, S and Elhai, JD and Sharp, C}, title = {The Independent Contributions of Emotion Dysregulation and Hypermentalization to the "Double Dissociation" of Affective and Cognitive Empathy in Female Adolescent Inpatients With BPD.}, journal = {Journal of personality disorders}, volume = {30}, number = {2}, pages = {242-260}, doi = {10.1521/pedi_2015_29_192}, pmid = {25905730}, issn = {1943-2763}, mesh = {Adolescent ; Affect/physiology ; Borderline Personality Disorder/*psychology ; Child ; Cognition/physiology ; Dissociative Disorders/*psychology ; Emotions/*physiology ; Empathy/*physiology ; Female ; Humans ; Inpatients/psychology/statistics & numerical data ; Multivariate Analysis ; }, abstract = {Harari, Shamay-Tsoory, Ravid, and Levkovitz (2010) demonstrated a "double dissociation" in empathy in borderline personality disorder (BPD), such that BPD patients had higher affective than cognitive empathy, whereas controls exhibited the opposite pattern. Two processes that may relate to this dissociation are emotion dysregulation (ER) and hypermentalization. However, these interrelated processes have not been studied concomitantly, and the dissociation of empathy types has not been examined in adolescents with BPD. This study examined the relations between ER, hypermentalization, and cognitive and affective empathy in 252 adolescent inpatients with and without BPD. Participants completed a computerized task of hypermentalization and measures of ER and empathy. Findings only partially replicated Harari et al.'s findings, with differential performance in cognitive and affective empathy demonstrated across groups. Multivariate analyses revealed that in both groups, ER related to increased affective empathy. Hypermentalizing related to decreased cognitive empathy in BPD patients, whereas hypermentalizing did not relate to either empathy type in non-BPD patients.}, } @article {pmid25904884, year = {2015}, author = {Bull, PN and Tippett, LJ and Addis, DR}, title = {Decision making in healthy participants on the Iowa Gambling Task: new insights from an operant approach.}, journal = {Frontiers in psychology}, volume = {6}, number = {}, pages = {391}, pmid = {25904884}, issn = {1664-1078}, abstract = {The Iowa Gambling Task (IGT) has contributed greatly to the study of affective decision making. However, researchers have observed high inter-study and inter-individual variability in IGT performance in healthy participants, and many are classified as impaired using standard criteria. Additionally, while decision-making deficits are often attributed to atypical sensitivity to reward and/or punishment, the IGT lacks an integrated sensitivity measure. Adopting an operant perspective, two experiments were conducted to explore these issues. In Experiment 1, 50 healthy participants completed a 200-trial version of the IGT which otherwise closely emulated Bechara et al.'s (1999) original computer task. Group data for Trials 1-100 closely replicated Bechara et al.'s original findings of high net scores and preferences for advantageous decks, suggesting that implementations that depart significantly from Bechara's standard IGT contribute to inter-study variability. During Trials 101-200, mean net scores improved significantly and the percentage of participants meeting the "impaired" criterion was halved. An operant-style stability criterion applied to individual data revealed this was likely related to individual differences in learning rate. Experiment 2 used a novel operant card task-the Auckland Card Task (ACT)-to derive quantitative estimates of sensitivity using the generalized matching law. Relative to individuals who mastered the IGT, persistent poor performers on the IGT exhibited significantly lower sensitivity to magnitudes (but not frequencies) of rewards and punishers on the ACT. Overall, our findings demonstrate the utility of operant-style analysis of IGT data and the potential of applying operant concurrent-schedule procedures to the study of human decision making.}, } @article {pmid25901187, year = {2015}, author = {Gilani, SZ and Tan, DW and Russell-Smith, SN and Maybery, MT and Mian, A and Eastwood, PR and Shafait, F and Goonewardene, M and Whitehouse, AJ}, title = {Sexually dimorphic facial features vary according to level of autistic-like traits in the general population.}, journal = {Journal of neurodevelopmental disorders}, volume = {7}, number = {1}, pages = {14}, pmid = {25901187}, issn = {1866-1947}, abstract = {BACKGROUND: In a recent study, Bejerot et al. observed that several physical features (including faces) of individuals with an autism spectrum disorder (ASD) were more androgynous than those of their typically developed counterparts, suggesting that ASD may be understood as a 'gender defiant' disorder. These findings are difficult to reconcile with the hypermasculinisation account, which proposes that ASD may be an exaggerated form of cognitive and biological masculinity. The current study extended these data by first identifying six facial features that best distinguished males and females from the general population and then examining these features in typically developing groups selected for high and low levels of autistic-like traits.

METHODS: In study 1, three-dimensional (3D) facial images were collected from 208 young adult males and females recruited from the general population. Twenty-three facial distances were measured from these images and a gender classification and scoring algorithm was employed to identify a set of six facial features that most effectively distinguished male from female faces. In study 2, measurements of these six features were compared for groups of young adults selected for high (n = 46) or low (n = 66) levels of autistic-like traits.

RESULTS: For each sex, four of the six sexually dimorphic facial distances significantly differentiated participants with high levels of autistic-like traits from those with low trait levels. All four features were less masculinised for high-trait males compared to low-trait males. Three of four features were less feminised for high-trait females compared to low-trait females. One feature was, however, not consistent with the general pattern of findings and was more feminised among females who reported more autistic-like traits. Based on the four significantly different facial distances for each sex, discriminant function analysis correctly classified 89.7% of the males and 88.9% of the females into their respective high- and low-trait groups.

CONCLUSIONS: The current data provide support for Bejerot et al.'s androgyny account since males and females with high levels of autistic-like traits generally showed less sex-typical facial features than individuals with low levels of autistic-like traits.}, } @article {pmid25900328, year = {2015}, author = {Lu, Y and Li, L and Peng, H and Xie, D and Yang, Y}, title = {Robust and efficient biometrics based password authentication scheme for telecare medicine information systems using extended chaotic maps.}, journal = {Journal of medical systems}, volume = {39}, number = {6}, pages = {65}, pmid = {25900328}, issn = {1573-689X}, mesh = {Biometric Identification/methods/*standards/trends ; Computer Security/instrumentation/*standards ; Confidentiality/*standards ; Health Information Systems/organization & administration/*standards/trends ; Health Smart Cards/*standards/trends ; Humans ; Patient Access to Records/*standards/trends ; Telemedicine/methods/*standards/trends ; }, abstract = {The Telecare Medicine Information Systems (TMISs) provide an efficient communicating platform supporting the patients access health-care delivery services via internet or mobile networks. Authentication becomes an essential need when a remote patient logins into the telecare server. Recently, many extended chaotic maps based authentication schemes using smart cards for TMISs have been proposed. Li et al. proposed a secure smart cards based authentication scheme for TMISs using extended chaotic maps based on Lee's and Jiang et al.'s scheme. In this study, we show that Li et al.'s scheme has still some weaknesses such as violation the session key security, vulnerability to user impersonation attack and lack of local verification. To conquer these flaws, we propose a chaotic maps and smart cards based password authentication scheme by applying biometrics technique and hash function operations. Through the informal and formal security analyses, we demonstrate that our scheme is resilient possible known attacks including the attacks found in Li et al.'s scheme. As compared with the previous authentication schemes, the proposed scheme is more secure and efficient and hence more practical for telemedical environments.}, } @article {pmid25899890, year = {2015}, author = {McManus, AL and Hoy, EP and Mazziotti, DA}, title = {Energies and structures in biradical chemistry from the parametric two-electron reduced-density matrix method: applications to the benzene and cyclobutadiene biradicals.}, journal = {Physical chemistry chemical physics : PCCP}, volume = {17}, number = {19}, pages = {12521-12529}, doi = {10.1039/c5cp01310k}, pmid = {25899890}, issn = {1463-9084}, abstract = {The treatment of biradical chemistry presents a challenge for electronic structure theory, especially single-reference methods, as it requires the description of varying degrees and kinds of electron correlation. In this work we assess the ability of the parametric two-electron reduced-density matrix (p2-RDM) method to describe biradical chemistry through application to the benzene and cyclobutadiene biradicals. The relative energy of o- and m-benzynes predicted by the p2-RDM method is consistent with Wenthold et al.'s experimental determinations, while the more difficult relative energy prediction of the more multi-referenced p-benzyne is within 1.4 kcal mol(-1) of the experimental value [P. G. Wenthold et al., J. Am. Chem. Soc., 1998, 120, 5279], which is significantly better than traditional single-reference methods. We observe that the degree of multireference correlation in the biradicals depends upon the distance between their radical centers, with the largest radical separation displaying the largest degree of multireference correlation. In addition to relative and absolute electronic energies, we report molecular geometries, natural orbitals, and natural-orbital occupations for the benzene and cyclobutadiene biradicals.}, } @article {pmid25899812, year = {2016}, author = {Khamis, NN and Satava, RM and Alnassar, SA and Kern, DE}, title = {A stepwise model for simulation-based curriculum development for clinical skills, a modification of the six-step approach.}, journal = {Surgical endoscopy}, volume = {30}, number = {1}, pages = {279-287}, pmid = {25899812}, issn = {1432-2218}, mesh = {*Clinical Competence ; Curriculum/*standards ; Humans ; *Models, Educational ; Specialties, Surgical/*education ; }, abstract = {BACKGROUND: Despite the rapid growth in the use of simulation in health professions education, courses vary considerably in quality. Many do not integrate efficiently into an overall school/program curriculum or conform to academic accreditation requirements. Moreover, some of the guidelines for simulation design are specialty specific.

STUDY DESIGN: We designed a model that integrates best practices for effective simulation-based training and a modification of Kern et al.'s 6-step approach for curriculum development. We invited international simulation and health professions education experts to complete a questionnaire evaluating the model. We reviewed comments and suggested modifications from respondents and reached consensus on a revised version of the model.

RESULTS: We recruited 17 simulation and education experts. They expressed a consensus on the seven proposed curricular steps: problem identification and general needs assessment, targeted needs assessment, goals and objectives, educational strategies, individual assessment/feedback, program evaluation, and implementation. We received several suggestions for descriptors that applied the steps to simulation, leading to some revisions in the model.

CONCLUSION: We have developed a model that integrates principles of curriculum development and simulation design that is applicable across specialties. Its use could lead to high-quality simulation courses that integrate efficiently into an overall curriculum.}, } @article {pmid25897706, year = {2015}, author = {Wald, HS}, title = {Refining a definition of reflection for the being as well as doing the work of a physician.}, journal = {Medical teacher}, volume = {37}, number = {7}, pages = {696-699}, doi = {10.3109/0142159X.2015.1029897}, pmid = {25897706}, issn = {1466-187X}, abstract = {BACKGROUND: Reflection is core to professional competency and supports the active, constructive process of professional identity formation.

AIMS: Medical educators thus grapple with operationalizing and effectively integrating reflection as a foundational construct within health care professions education and practice.

METHODS: Core elements of reflection including role of emotions and awareness of self, other and situation, do not appear within various working definitions of reflection.

RESULTS: This observation as well as noted recent shift in medical education toward emphasis on the "being" as well as "doing the work" of a physician led to the author's proposed refining of Sandars' reflection definition and expansion of Nguyen et al.'s reflection model.

CONCLUSIONS: A refined reflection definition is offered for a more inclusionary approach. A caveat regarding potential for expected reflective learning outcomes (given reflection as a process) is provided and the integral role of mentor-enhanced reflection is discussed. Reflection as a continuum is highlighted and exemplified within Wald et al.'s REFLECT rubric and Nguyen et al.'s reflection model.}, } @article {pmid25888606, year = {2017}, author = {Cook, BG and Dupuis, DN and Jitendra, AK}, title = {A Preliminary Investigation of the Empirical Validity of Study Quality Appraisal.}, journal = {Journal of learning disabilities}, volume = {50}, number = {1}, pages = {14-22}, doi = {10.1177/0022219415581178}, pmid = {25888606}, issn = {1538-4780}, mesh = {Educational Measurement/*standards ; *Evaluation Studies as Topic ; Humans ; *Learning Disabilities ; Reproducibility of Results ; *Review Literature as Topic ; }, abstract = {When classifying the evidence base of practices, special education scholars typically appraise study quality to identify and exclude from consideration in their reviews unacceptable-quality studies that are likely biased and might bias review findings if included. However, study quality appraisals used in the process of identifying evidence-based practices for students with learning and other disabilities have not been empirically validated (e.g., studies classified as unacceptable quality shown to have different, and presumably more biased, effects than high-quality studies). Using Gersten et al.'s (2005) approach for appraising the quality of group experimental studies in special education, we examined whether (a) studies classified as unacceptable quality and high quality had meaningfully different effects and (b) unacceptable-quality studies were more likely to have outlying effects than high-quality studies among 36 group experimental studies that investigated the effectiveness of instructional practices for students with learning disabilities. Our preliminary analyses found that the effects of unacceptable-quality studies were not meaningfully different from the effects of high-quality studies. We discuss implications of these findings and call for more research to be conducted in this area.}, } @article {pmid25867696, year = {2015}, author = {Lewis, JA and Neville, HA}, title = {Construction and initial validation of the Gendered Racial Microaggressions Scale for Black women.}, journal = {Journal of counseling psychology}, volume = {62}, number = {2}, pages = {289-302}, doi = {10.1037/cou0000062}, pmid = {25867696}, issn = {0022-0167}, mesh = {Adolescent ; Adult ; Black or African American/*psychology ; Aged ; Aggression/*psychology ; Factor Analysis, Statistical ; Female ; Focus Groups ; Humans ; Middle Aged ; Models, Psychological ; Racism/*psychology ; Sexism/*psychology ; Sexual Behavior/*psychology ; *Stereotyping ; Stress, Psychological/psychology ; Young Adult ; }, abstract = {The purpose of this study was to develop a measure of gendered racial microaggressions (i.e., subtle and everyday verbal, behavioral, and environmental expressions of oppression based on the intersection of one's race and gender) experienced by Black women by applying an intersectionality framework to Essed's (1991) theory of gendered racism and Sue, Capodilupo, et al.'s (2007) model of racial microaggressions. The Gendered Racial Microaggressions Scale (GRMS), was developed to assess both frequency and stress appraisal of microaggressions, in 2 separate studies. After the initial pool of GRMS items was developed, we received input from a community-based focus group of Black women and an expert panel. In Study 1, an exploratory factor analysis using a sample of 259 Black women resulted in a multidimensional scale with 4 factors as follows: (a) Assumptions of Beauty and Sexual Objectification, (b) Silenced and Marginalized, (c) Strong Black Woman Stereotype, and (d) Angry Black Woman Stereotype. In Study 2, results of confirmatory factor analyses using an independent sample of 210 Black women suggested that the 4-factor model was a good fit of the data for both the frequency and stress appraisal scales. Supporting construct validity, the GRMS was positively related to the Racial and Ethnic Microaggressions Scale (Nadal, 2011) and the Schedule of Sexist Events (Klonoff & Landrine, 1995). In addition, the GRMS was significantly related to psychological distress, such that greater perceived gendered racial microaggressions were related to greater levels of reported psychological distress. Implications for future research and practice are discussed.}, } @article {pmid25860925, year = {2015}, author = {Clarke, C and Eales-Reynolds, LJ}, title = {Human factors paradigm and customer care perceptions.}, journal = {International journal of health care quality assurance}, volume = {28}, number = {3}, pages = {288-299}, doi = {10.1108/IJHCQA-05-2014-0067}, pmid = {25860925}, issn = {0952-6862}, mesh = {*Attitude of Health Personnel ; Communication ; Efficiency, Organizational ; Female ; Humans ; Male ; Models, Organizational ; *Organizational Culture ; Organizational Objectives ; *Patient Safety ; *Quality Improvement ; State Medicine ; Surveys and Questionnaires ; United Kingdom ; }, abstract = {PURPOSE: The purpose of this paper is to examine if customer care (CC) can be directly linked to patient safety through a human factors (HF) framework.

DESIGN/METHODOLOGY/APPROACH: Data from an online questionnaire, completed by a convenience healthcare worker sample (n=373), was interrogated using thematic analysis within Vincent et al.'s (1998) HF theoretical framework. This proposes seven areas affecting patient safety: institutional context, organisation and management, work environment, team factors, individual, task and patient.

FINDINGS: Analysis identified responses addressing all framework areas. Responses (597) principally focused on work environment 40.7 per cent (n=243), organisation and management 28.8 per cent (n=172). Nevertheless, reference to other framework areas were clearly visible within the data: teams 10.2 per cent (n=61), individual 6.7 per cent (n=40), patients 6.0 per cent (n=36), tasks 4.2 per cent (n=24) and institution 3.5 per cent (n=21). Findings demonstrate congruence between CC perceptions and patient safety within a HF framework.

The questionnaire requested participants to identify barriers to rather than CC enablers. Although this was at a single site complex organisation, it was similar to those throughout the NHS and other international health systems.

PRACTICAL IMPLICATIONS: CC can be viewed as consonant with patient safety rather than the potentially dangerous consumerisation stance, which could ultimately compromise patient safety.

ORIGINALITY/VALUE: This work provides an original perspective on the link between CC and patient safety and has the potential to re-focus healthcare perceptions.}, } @article {pmid25860862, year = {2015}, author = {Omodaka, K and Takada, N and Yamaguchi, T and Takahashi, H and Araie, M and Nakazawa, T}, title = {Characteristic correlations of the structure-function relationship in different glaucomatous disc types.}, journal = {Japanese journal of ophthalmology}, volume = {59}, number = {4}, pages = {223-229}, pmid = {25860862}, issn = {1613-2246}, mesh = {Adult ; Aged ; Female ; Glaucoma, Open-Angle/classification/*physiopathology ; Humans ; Intraocular Pressure/physiology ; Low Tension Glaucoma/classification/*physiopathology ; Male ; Middle Aged ; Nerve Fibers/*pathology ; Optic Disk/*pathology ; Optic Nerve Diseases/classification/*physiopathology ; Retinal Ganglion Cells/*pathology ; Tomography, Optical Coherence ; Tonometry, Ocular ; Visual Field Tests ; Visual Fields/physiology ; }, abstract = {PURPOSE: To investigate the influence of the optic disc type on the overall and regional correlation between structure and function in open angle glaucoma (OAG).

METHODS: We divided 144 eyes of 144 patients with OAG into four groups according to Nicolela et al.'s classification of optic disc type: focal ischemic (FI), myopic glaucomatous (MY), senile sclerotic (SS), and generalized enlargement (GE). We measured the circumpapillary retinal nerve fiber layer thickness (cpRNFLT) with the 3D OCT-2000 and the mean deviation (MD) with the Humphrey Field Analyzer in each group and determined the influence of the disc type on these parameters with the Spearman rank correlation.

RESULTS: We found that cpRNFLT and MD were significantly correlated in the MY (r = 0.61, P < 0.001), GE (r = 0.62, P < 0.001), and SS groups (r = 0.52, P = 0.002), but not in the FI group (r = 0.25, P = 0.130). The region of the optic disc with the highest correlation coefficient between structure and function differed according to the disc type.

CONCLUSIONS: The correlation between cpRNFLT and MD varied according to the optic disc morphology in OAG. This suggests that different disc types have characteristic regional variations in the correlation between structure and function. The disc type should therefore be considered in investigations of the correlation between structure and function in glaucoma.}, } @article {pmid25853224, year = {2015}, author = {Watling, D}, title = {Children's judgements of social withdrawal behaviours.}, journal = {The British journal of developmental psychology}, volume = {33}, number = {2}, pages = {180-182}, doi = {10.1111/bjdp.12088}, pmid = {25853224}, issn = {2044-835X}, mesh = {Child Behavior/*ethnology ; Female ; Humans ; *Interpersonal Relations ; Male ; *Shyness ; Social Isolation/*psychology ; *Social Perception ; }, abstract = {Ding et al. (Brit. J. Dev. Psychol., 2015; 33, 159-173) demonstrated that Chinese children discriminate between the three subtypes of social withdrawal: Shyness, unsociability, and social avoidance. This commentary on the Ding et al.'s paper highlights the need to further explore the following: (1) children's understanding of the implications of being shy, unsociable, or socially avoidant, including assessing these which we know are associated with outcomes for socially withdrawn children; (2) what additional subtypes might exist naturally within the Chinese culture; and (3) consider the implications of social withdrawal on children's developing social skills.}, } @article {pmid25833463, year = {2015}, author = {Mynard, JP and Valen-Sendstad, K}, title = {A unified method for estimating pressure losses at vascular junctions.}, journal = {International journal for numerical methods in biomedical engineering}, volume = {31}, number = {7}, pages = {e02717}, doi = {10.1002/cnm.2717}, pmid = {25833463}, issn = {2040-7947}, mesh = {Algorithms ; Blood Flow Velocity/*physiology ; Blood Pressure/*physiology ; *Computer Simulation ; *Models, Cardiovascular ; Pulsatile Flow/*physiology ; }, abstract = {In reduced-order (0D/1D) blood or respiratory flow models, pressure losses at junctions are usually neglected. However, these may become important where velocities are high and significant flow redirection occurs. Current methods for estimating losses rely on relatively complex empirical equations that are only valid for specific junction geometries and flow regimes. In pulsatile multi-directional flows, switching between empirical equations upon reversing flow may introduce unrealistic discontinuities in simulated haemodynamic waveforms. Drawing from work by Bassett et al. (SAE Trans 112:565-583, 2003), we therefore developed a unified method (Unified0D) for estimating loss coefficients that can be applied to any junction (i.e. any number of branches at any angle) and any flow regime. Discontinuities in simulated waveforms were avoided by extending Bassett et al.'s control volume-based method to incorporate a 'pseudodatum' supplier branch, an imaginary effective vessel containing all inflow to the junction. Energy exchange between diverging flow streams was also accounted for empirically. The formulation was validated using high resolution computational fluid dynamics in a wide range flow conditions and junction configurations. In a pulsatile 1D simulation exhibiting transitions between four different flow regimes, the new formulation produced smooth transitions in calculated pressure losses.}, } @article {pmid25823920, year = {2016}, author = {Logačev, P and Vasishth, S}, title = {A Multiple-Channel Model of Task-Dependent Ambiguity Resolution in Sentence Comprehension.}, journal = {Cognitive science}, volume = {40}, number = {2}, pages = {266-298}, doi = {10.1111/cogs.12228}, pmid = {25823920}, issn = {1551-6709}, mesh = {Comprehension/*physiology ; Humans ; *Language ; *Models, Theoretical ; Psycholinguistics ; Reaction Time/physiology ; *Reading ; }, abstract = {Traxler, Pickering, and Clifton (1998) found that ambiguous sentences are read faster than their unambiguous counterparts. This so-called ambiguity advantage has presented a major challenge to classical theories of human sentence comprehension (parsing) because its most prominent explanation, in the form of the unrestricted race model (URM), assumes that parsing is non-deterministic. Recently, Swets, Desmet, Clifton, and Ferreira (2008) have challenged the URM. They argue that readers strategically underspecify the representation of ambiguous sentences to save time, unless disambiguation is required by task demands. When disambiguation is required, however, readers assign sentences full structure--and Swets et al. provide experimental evidence to this end. On the basis of their findings, they argue against the URM and in favor of a model of task-dependent sentence comprehension. We show through simulations that the Swets et al. data do not constitute evidence for task-dependent parsing because they can be explained by the URM. However, we provide decisive evidence from a German self-paced reading study consistent with Swets et al.'s general claim about task-dependent parsing. Specifically, we show that under certain conditions, ambiguous sentences can be read more slowly than their unambiguous counterparts, suggesting that the parser may create several parses, when required. Finally, we present the first quantitative model of task-driven disambiguation that subsumes the URM, and we show that it can explain both Swets et al.'s results and our findings.}, } @article {pmid25822243, year = {2015}, author = {Flückiger, C and Del Re, AC and Wampold, BE}, title = {The sleeper effect: Artifact or phenomenon-A brief comment on Bell et al. (2013).}, journal = {Journal of consulting and clinical psychology}, volume = {83}, number = {2}, pages = {438-42; discussion 443-4}, doi = {10.1037/a0037220}, pmid = {25822243}, issn = {1939-2117}, mesh = {Humans ; *Models, Psychological ; *Treatment Outcome ; }, abstract = {OBJECTIVE: Bell, Marcus, and Goodlad (2013) recently conducted a meta-analysis of randomized controlled additive trials and found that adding an additional component to an existing treatment vis-à-vis the existing treatment produced larger effect sizes on targeted outcomes at 6-months follow-up than at termination, an effect they labeled as a sleeper effect. One of the limitations with Bell et al.'s detection of the sleeper effect was that they did not conduct a statistical test of the size of the effect at follow-up versus termination.

METHOD: To statistically test if the differences of effect sizes between the additive conditions and the control conditions at follow-up differed from those at termination, we used a restricted maximum-likelihood random-effect model with known variances to conduct a multilevel longitudinal meta-analysis (k = 30).

RESULTS: Although the small effects at termination detected by Bell et al. were replicated (ds = 0.17-0.23), none of the analyses of growth from termination to follow-up produced statistically significant effects (ds < 0.08; p > .20), and when asymmetry was considered using trim-and-fill procedure or the studies after 2000 were analyzed, magnitude of the sleeper effect was negligible (d = 0.00).

CONCLUSION: There is no empirical evidence to support the sleeper effect. (PsycINFO Database Record}, } @article {pmid25808672, year = {2015}, author = {Chopko, BA and Palmieri, PA and Adams, RE}, title = {Critical incident history questionnaire replication: frequency and severity of trauma exposure among officers from small and midsize police agencies.}, journal = {Journal of traumatic stress}, volume = {28}, number = {2}, pages = {157-161}, doi = {10.1002/jts.21996}, pmid = {25808672}, issn = {1573-6598}, mesh = {Adult ; Female ; Humans ; Male ; Mental Health ; Middle Aged ; *Occupational Exposure ; Police/*psychology ; Psychometrics ; Risk Factors ; Rural Population ; Stress Disorders, Post-Traumatic/etiology ; Stress, Psychological/psychology ; *Surveys and Questionnaires ; Trauma Severity Indices ; Workplace Violence/psychology ; Wounds and Injuries/psychology ; Young Adult ; }, abstract = {Frequency and severity of trauma exposure are thought to influence posttraumatic reactions. Weiss et al.'s Critical Incident History Questionnaire (CIHQ; 2010) measures these variables among law enforcement officers; they reported findings using a sample of officers from large urban departments. We noted the need for replication studies utilizing samples from smaller and rural police agencies. The purpose of this study was to replicate the CIHQ findings from Weiss et al. using a sample (N = 193) of officers from small and midsize police departments and officers whose duties include policing rural and isolated jurisdictions. Frequency and severity findings were similar to those reported by Weiss et al. (). Regarding frequency, the present study found the critical incident exposure mean score was 188.5, compared to 168.5 from Weiss et al. (). Making a mistake that kills or injures a colleague had the highest mean nomothetic severity rating in both studies. Among the various variables examined in this study, PTSD symptoms demonstrated the strongest association with the exposure indices, based on Spearman rank correlations (r = .26-.46).}, } @article {pmid25808040, year = {2015}, author = {Levin, FR and Mariani, JJ and Bisaga, A and Nunes, EV}, title = {Ling et al.'s 'Sustained-release methylphenidate in a randomized trial of treatment of methamphetamine use disorder'.}, journal = {Addiction (Abingdon, England)}, volume = {110}, number = {5}, pages = {875-876}, pmid = {25808040}, issn = {1360-0443}, support = {K24 DA029647/DA/NIDA NIH HHS/United States ; }, mesh = {Amphetamine-Related Disorders/*drug therapy ; Central Nervous System Stimulants/*therapeutic use ; Female ; Humans ; Male ; Methylphenidate/*therapeutic use ; }, } @article {pmid25806521, year = {2015}, author = {Sun, X and Xu, D and Luo, F and Wei, Z and Wei, C and Xue, G}, title = {A cross-cultural perspective on the preference for potential effect: an individual participant data (IPD) meta-analysis approach.}, journal = {PloS one}, volume = {10}, number = {3}, pages = {e0124170}, pmid = {25806521}, issn = {1932-6203}, mesh = {China ; *Choice Behavior ; *Cross-Cultural Comparison ; Humans ; *Social Behavior ; United States ; }, abstract = {A recent paper [Tormala ZL, Jia JS, Norton MI (2012). The preference for potential. Journal of personality and social psychology, 103: 567-583] demonstrated that persons often prefer potential rather than achievement when evaluating others, because information regarding potential evokes greater interest and processing, resulting in more favorable evaluations. This research aimed to expand on this finding by asking two questions: (a) Is the preference for potential effect replicable in other cultures? (b) Is there any other mechanism that accounts for this preference for potential? To answer these two questions, we replicated Tormala et al.'s study in multiple cities (17 studies with 1,128 participants) in China using an individual participant data (IPD) meta-analysis approach to test our hypothesis. Our results showed that the preference for potential effect found in the US is also robust in China. Moreover, we also found a pro-youth bias behind the preference for potential effect. To be specific, persons prefer a potential-oriented applicant rather than an achievement-oriented applicant, partially because they believe that the former is younger than the latter.}, } @article {pmid25806085, year = {2015}, author = {Marais, DL and Petersen, I}, title = {Health system governance to support integrated mental health care in South Africa: challenges and opportunities.}, journal = {International journal of mental health systems}, volume = {9}, number = {}, pages = {14}, pmid = {25806085}, issn = {1752-4458}, abstract = {BACKGROUND: While South Africa has a new policy framework supporting the integration of mental health care into primary health care, this is not sufficient to ensure transformation of the health care system towards integrated primary mental health care. Health systems strengthening is needed, incorporating, inter alia, capacity building and resource inputs, as well as good governance for ensuring that the relevant policy imperatives are implemented.

OBJECTIVES: To identify systemic factors within institutional and policy contexts that are likely to facilitate or impede the implementation of integrated mental health care in South Africa.

METHODS: Semi-structured qualitative interviews were conducted with 17 key stakeholders in the Department of Health and Department of Social Development at national level, at provincial level in the North West Province, and at district level in the Dr Kenneth Kaunda district. Participants were purposively identified based on their positions and job responsibilities. Interview questions were guided by a hybrid of Siddiqi et al.'s governance framework principles and Mikkelsen-Lopez et al.'s health system governance approach. Data were analysed using framework analysis in NVivo.

RESULTS: Facilitative factors included the recent mental health care policy framework and national action plan that embraces integrated care using a task sharing model and provides policy imperatives for the establishment of district mental health teams to facilitate the development and implementation of district mental health care plans; the roll out of the integrated chronic disease service delivery platform that can be leveraged to increase access and resources as well as decrease stigma; and the presence of NGOs that can assist with service delivery. Challenges included the low prioritisation and stigmatisation of mental illness; weak managerial and planning capacity to develop and implement mental health care plans at provincial and district level; poor pre-service training of generalists in mental health care; weak orientation to integrated care; high staff turnover; weak intersectoral coordination; infrastructural constraints; and no dedicated mental health budget.

CONCLUSION: This study identifies strategies to support and improve integrated mental health care in primary health care services.}, } @article {pmid25802199, year = {2016}, author = {Silva, AM and Pereira, ML and Gouveia, S and Tavares, JN and Azevedo, Á and Caldas, IM}, title = {A new approach to sex estimation using the mandibular canine index.}, journal = {Medicine, science, and the law}, volume = {56}, number = {1}, pages = {7-12}, doi = {10.1177/0025802415575415}, pmid = {25802199}, issn = {2042-1818}, mesh = {Adolescent ; Adult ; Cuspid/*anatomy & histology ; Female ; Forensic Dentistry ; Humans ; Male ; Mandible ; Models, Dental ; Odontometry ; Portugal ; ROC Curve ; *Sex Determination Analysis ; Young Adult ; }, abstract = {Rao et al.'s mandibular canine index (MCI) is a simple odontometric method which uses the mandibular canine as the key to sex estimation. This index is defined as the ratio between the right canine mesiodistal dimension and the mandibular canine arch width. The aim of this study was to contribute to sex estimation using dental techniques by analysing the MCI efficiency, and to propose a new approach for its use. Measurements were taken from 120 plaster casts (70 females) in the 16-30 year age group. Although statistically significant sexual dimorphism was observed in both the mesiodistal dimension and the mandibular canine arch width, the MCI showed a low accuracy in sex classification (54.2% correct identifications). This accuracy was improved to 64.2% using receiver operating characteristics curve analysis. Yet, despite the better accuracy, these results reinforce the idea that the MCI may not be particularly useful in sex prediction, since it may not reflect the same degree of sexual dimorphism as its absolute measures.}, } @article {pmid25794940, year = {2015}, author = {Sakowski, SA and Feldman, EL}, title = {The Spectrum of Motor Neuron Diseases: From Childhood Spinal Muscular Atrophy to Adult Amyotrophic Lateral Sclerosis.}, journal = {Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics}, volume = {12}, number = {2}, pages = {287-289}, pmid = {25794940}, issn = {1878-7479}, mesh = {Adult ; *Amyotrophic Lateral Sclerosis ; Child ; Child, Preschool ; Humans ; *Motor Neuron Disease ; *Muscular Atrophy, Spinal ; }, } @article {pmid25785544, year = {2015}, author = {Silk-Eglit, GM and Miele, AS and Stenclik, JH and Lynch, JK and McCaffrey, RJ}, title = {Evaluation of the Generalizability of the Number of Abnormal Scores and the Overall Test Battery Mean as Measures of Performance Validity to a Different Test Battery.}, journal = {Applied neuropsychology. Adult}, volume = {22}, number = {6}, pages = {399-406}, doi = {10.1080/23279095.2014.949719}, pmid = {25785544}, issn = {2327-9109}, mesh = {Adult ; Brain Injuries/*complications ; Cognition Disorders/*diagnosis/*etiology ; Data Curation/statistics & numerical data ; Disability Evaluation ; Female ; Humans ; Male ; Middle Aged ; *Neuropsychological Tests ; Psychometrics ; Reference Values ; Reproducibility of Results ; Sensitivity and Specificity ; }, abstract = {Davis, Axelrod, McHugh, Hanks, and Millis (2013) documented that in a battery of 25 tests, producing 15, 10, and 5 abnormal scores at 1, 1.5, and 2 standard deviations below the norm-referenced mean, respectively, and an overall test battery mean (OTBM) of T ≤ 38 accurately identifies performance invalidity. However, generalizability of these findings to other samples and test batteries remains unclear. This study evaluated the use of abnormal scores and the OTBM as performance validity measures in a different sample that was administered a 25-test battery that minimally overlapped with Davis et al.'s test battery. Archival analysis of 48 examinees with mild traumatic brain injury seen for medico-legal purposes was conducted. Producing 18 or more, 7 or more, and 5 or more abnormal scores at 1, 1.5, and 2 standard deviations below the norm-referenced mean, respectively, and an OTBM of T ≤ 40 most accurately classified examinees; however, using Davis et al.'s proposed cutoffs in the current sample maintained specificity at or near acceptable levels. Due to convergence across studies, producing ≥5 abnormal scores at 2 standard deviations below the norm-referenced mean is the most appropriate cutoff for clinical implementation; however, for batteries consisting of a different quantity of tests than 25, an OTBM of T ≤ 38 is more appropriate.}, } @article {pmid25781510, year = {2015}, author = {Garcia-Alfaro, J and Herrera-Joancomartí, J and Melià-Seguí, J}, title = {Remarks on Peinado et al.'s Analysis of J3Gen.}, journal = {Sensors (Basel, Switzerland)}, volume = {15}, number = {3}, pages = {6217-6220}, pmid = {25781510}, issn = {1424-8220}, abstract = {Peinado et al. analyzed the security of the J3Gen pseudorandom number generator proposed by Melià-Seguí et al., and claimed weaknesses regarding its security properties. They also presented a deterministic attack based on the decimation of the J3Gen output sequences. We show that the assumptions made by Peinado et al. are not correct and that the proposed deterministic attack against J3Gen does not hold in practice.}, } @article {pmid25774128, year = {2015}, author = {Sanders, N and Smeets, PA and van Elburg, AA and Danner, UN and van Meer, F and Hoek, HW and Adan, RA}, title = {Altered food-cue processing in chronically ill and recovered women with anorexia nervosa.}, journal = {Frontiers in behavioral neuroscience}, volume = {9}, number = {}, pages = {46}, pmid = {25774128}, issn = {1662-5153}, abstract = {Anorexia nervosa (AN) is a severe mental disorder characterized by food restriction and weight loss. This study aimed to test the model posed by Brooks et al. (2012a,b) that women suffering from chronic AN show decreased food-cue processing activity in brain regions associated with energy balance and food reward (bottom-up; BU) and increased activity in brain regions associated with cognitive control (top-down; TD) when compared with long-term recovered AN (REC) and healthy controls (HC). Three groups of women, 15 AN (mean illness duration 7.8 ± 4.1 years), 14 REC (mean duration of recovery 4.7 ± 2.7 years) and 15 HC viewed alternating blocks of food and non-food images preceded by a short instruction during functional magnetic resonance imaging (fMRI), after fasting overnight. Functional region of interests (fROIs) were defined in BU (e.g., striatum, hippocampus, amygdala, hypothalamus, and cerebellum), TD (e.g., medial and lateral prefrontal cortex, and anterior cingulate), the insula, and visual processing areas (VPA). Food-cue processing activation was extracted from all fROIs and compared between the groups. In addition, functional connectivity between the fROIs was examined by modular partitioning of the correlation matrix of all fROIs. We could not confirm the hypothesis that BU areas are activated to a lesser extent in AN upon visual processing of food images. Among the BU areas the caudate showed higher activation in both patient groups compared to HC. In accordance with Brooks et al.'s model, we did find evidence for increased TD control in AN and REC. The functional connectivity analysis yielded two clusters in HC and REC, but three clusters in AN. In HC, fROIs across BU, TD, and VPA areas clustered; in AN, one cluster span across BU, TD, and insula; one across BU, TD, and VPA areas; and one was confined to the VPA network. In REC, BU, TD, and VPA or VPA and insula clustered. In conclusion, despite weight recovery, neural processing of food cues is also altered in recovered AN patients.}, } @article {pmid25772671, year = {2016}, author = {Campbell, SJ and Raney, GE}, title = {A 25-year replication of Katz et al.'s (1988) metaphor norms.}, journal = {Behavior research methods}, volume = {48}, number = {1}, pages = {330-340}, doi = {10.3758/s13428-015-0575-2}, pmid = {25772671}, issn = {1554-3528}, mesh = {*Comprehension ; Humans ; Individuality ; *Language ; *Metaphor ; Reproducibility of Results ; }, abstract = {Research in metaphor processing has made extensive use of the normed metaphor database created by Katz, Paivio, Marschark, & Clark (Metaphor and Symbolic Activity, 3, 191-214, 1988). Because of the plasticity of figurative language, we conducted a renorming of selected metaphors from the database on a new student population. Correlations between Katz et al.'s and the present data showed that the pattern of responses has remained highly consistent across time and populations. The consistency of the normative ratings allows us to be confident in future research that will use the Katz et al. collection.}, } @article {pmid25763409, year = {2015}, author = {Naderi, T and Foroodnia, S and Omidi, S and Samadani, F and Nakhaee, N}, title = {Incidence and correlates of maternal near miss in southeast iran.}, journal = {International journal of reproductive medicine}, volume = {2015}, number = {}, pages = {914713}, pmid = {25763409}, issn = {2356-7104}, abstract = {This prospective study aimed to estimate the incidence and associated factors of severe maternal morbidity in southeast Iran. During a 9-month period in 2013, all women referring to eight hospitals for termination of pregnancy as well as women admitted during 42 days after the termination of pregnancy were enrolled into the study. Maternal near miss conditions were defined based on Say et al.'s recommendations. Five hundred and one cases of maternal near miss and 19,908 live births occurred in the study period, yielding a maternal near miss ratio of 25.2 per 1000 live births. This rate was 7.5 and 105 per 1000 in private and tertiary care settings, respectively. The rate of maternal death in near miss cases was 0.40% with a case:fatality ratio of 250 : 1. The most prevalent causes of near miss were severe preeclampsia (27.3%), ectopic pregnancy (18.4%), and abruptio placentae (16.2%). Higher age, higher education, and being primiparous were associated with a higher risk of near miss. Considering the high rate of maternal near miss in referral hospitals, maternal near miss surveillance system should be set up in these hospitals to identify cases of severe maternal morbidity as soon as possible.}, } @article {pmid25754532, year = {2015}, author = {Wakefield, JC}, title = {Symptom data reanalysis disconfirms Parker et al.'s claim that latent class analysis identifies melancholic depression.}, journal = {Acta psychiatrica Scandinavica}, volume = {132}, number = {4}, pages = {306-307}, doi = {10.1111/acps.12413}, pmid = {25754532}, issn = {1600-0447}, mesh = {Bipolar Disorder/*diagnosis ; Depressive Disorder/*diagnosis ; Female ; Humans ; Male ; }, } @article {pmid25750176, year = {2015}, author = {Mishra, R and Barnwal, AK}, title = {A privacy preserving secure and efficient authentication scheme for telecare medical information systems.}, journal = {Journal of medical systems}, volume = {39}, number = {5}, pages = {54}, pmid = {25750176}, issn = {1573-689X}, mesh = {*Computer Security ; Confidentiality ; Health Information Exchange ; Humans ; Medical Records Systems, Computerized/*organization & administration/standards ; Telemedicine/*organization & administration/standards ; }, abstract = {The Telecare medical information system (TMIS) presents effective healthcare delivery services by employing information and communication technologies. The emerging privacy and security are always a matter of great concern in TMIS. Recently, Chen at al. presented a password based authentication schemes to address the privacy and security. Later on, it is proved insecure against various active and passive attacks. To erase the drawbacks of Chen et al.'s anonymous authentication scheme, several password based authentication schemes have been proposed using public key cryptosystem. However, most of them do not present pre-smart card authentication which leads to inefficient login and password change phases. To present an authentication scheme with pre-smart card authentication, we present an improved anonymous smart card based authentication scheme for TMIS. The proposed scheme protects user anonymity and satisfies all the desirable security attributes. Moreover, the proposed scheme presents efficient login and password change phases where incorrect input can be quickly detected and a user can freely change his password without server assistance. Moreover, we demonstrate the validity of the proposed scheme by utilizing the widely-accepted BAN (Burrows, Abadi, and Needham) logic. The proposed scheme is also comparable in terms of computational overheads with relevant schemes.}, } @article {pmid25735550, year = {2015}, author = {Hunter, DJ and Erskine, J and Small, A and McGovern, T and Hicks, C and Whitty, P and Lugsden, E}, title = {Doing transformational change in the English NHS in the context of "big bang" redisorganisation.}, journal = {Journal of health organization and management}, volume = {29}, number = {1}, pages = {10-24}, doi = {10.1108/JHOM-01-2014-0019}, pmid = {25735550}, issn = {1477-7266}, support = {MR/K02325X/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {England ; Focus Groups ; *Health Care Reform ; Hospitals, Public ; Interviews as Topic ; Organizational Innovation ; Qualitative Research ; Quality Improvement ; State Medicine/*organization & administration ; }, abstract = {PURPOSE: The purpose of this paper is to examine a bold and ambitious scheme known as the North East transformation system (NETS). The principal aim of the NETS is the achievement of a step-change in the quality of health services delivered to people living in the North East region of England. The paper charts the origins of the NETS and its early journey before describing what happened to it when the UK coalition government published its proposals for unexpected major structural change in the NHS. This had a profound impact on the leadership and direction of the NETS and resulted in it taking a different direction from that intended.

DESIGN/METHODOLOGY/APPROACH: The research design took the form of a mixed methods, longitudinal 3.5-year study aimed at exploring transformational change in terms of content, context, process and outcomes. The sample of study sites comprised 14 NHS trusts in the North East region chosen to provide geographical coverage of the area and to reflect the scale, scope and variety of the bodies that formed part of the NETS programme. The qualitative component of the research, which the paper draws upon, included 68 semi-structured interviews, observational studies and focus groups. Data analysis made use of both deductive and inductive frameworks. The deductive framework adopted was Pettigrew et al.'s "receptive contexts for change" and four of the eight factors stood out as especially important and form the basis of the paper.

FINDINGS: The fate of the NETS was shaped and influenced by the eight factors comprising the Pettigrew et al. receptive contexts for change framework but four factors in particular stood out as being especially significant: environmental pressure, quality and coherence of policy, key people leading change, supportive organisational culture. Perhaps the most significant lesson from the NETS is that achieving whole systems change is particularly vulnerable to the vicissitudes of politics especially where that system, like the UK NHS, is itself subject to those very same pressures. Yet, despite having an enormous influence on health policy, the political context is frequently avoided in research or not regarded as instrumental in determining the outcomes in respect of transformational change.

The chief limitation is the credibility and authenticity of the interviews captured at particular points in time. These formed the datebase for subsequent analysis. The authors sought to guard against possible bias by supplementing interviews with observational studies and focus groups as well as running two dissemination events at which emerging findings from the study were subjected to independent external scrutiny and comment. These events provided a form of validation for the key study findings.

PRACTICAL IMPLICATIONS: The research findings demonstrate the importance of context for the likely outcome and success of complex transformational change initiatives. These require time to become embedded and demonstrate results especially when focused on changing culture and behaviour. But, in practice, allowing sufficient time during which the organisation may remain sufficiently stable to allow the change intervention to run its course and become embedded and sustainable is highly problematic. The consequence is that bold and ambitious efforts like the NETS are not given the space and stability to prove themselves. Too often, politics and external environmental pressures intrude in ways that may prove dysfunctional and negative.

SOCIAL IMPLICATIONS: Unless a different approach to transformational change and its leadership and management is adopted, then changing the NHS to enable it to appear more responsive to changing health care needs and expectations will remain a cause for concern. Ultimately the public will be the losers if the NHS remains insensitive to changing needs and expectations. The patient experience was at the centre of the NETS programme.

ORIGINALITY/VALUE: The study is original insofar as no other has sought to evaluate the NETS independently and over a reasonable time period. The research design, based on a mixed-methods approach, is unusual in evaluations of this nature. The study's conclusions are not so original but their value lies in largely confirming and reinforcing the findings from other studies. It perhaps goes further in stressing the impact of politics on health policy and the negative consequences of constant organisational change on attempts to achieve deep change in the way the NHS is organised and led.}, } @article {pmid25734862, year = {2015}, author = {Foxlee, N and Stone, JC and Doi, SA}, title = {A comparison of univariate and bivariate models in meta-analysis of diagnostic accuracy studies.}, journal = {International journal of evidence-based healthcare}, volume = {13}, number = {1}, pages = {28-34}, doi = {10.1097/XEB.0000000000000037}, pmid = {25734862}, issn = {1744-1609}, mesh = {Data Interpretation, Statistical ; *Diagnosis ; Humans ; *Meta-Analysis as Topic ; *Models, Statistical ; Quality Assurance, Health Care ; Sensitivity and Specificity ; }, abstract = {AIM: : An implicit diagnostic threshold has been thought to be the cause of between-study variation in meta-analyses of diagnostic accuracy studies. Bivariate models have been used to account for implicit diagnostic thresholds. However, little difference in estimates of test performance has been reported between univariate and bivariate models. This study aims to undertake another comparison of these two models in order to determine if spectrum effects could better explain the variation across studies.

METHODS: Studies were selected from those provided in Ohle et al.'s meta-analysis and quality scored using QUADAS 2. Univariate analyses of sensitivity and specificity were computed using two models: one bias-adjusted and the other not. The univariate sensitivity and specificity results were compared with the bivariate logit-normal summary ROC method.

RESULTS: Similar results were obtained when using summary ROC and univariate pooling methods for sensitivity and specificity. Differences in study characteristics were found for outlier studies in univariate analyses, suggesting spectrum effects.

CONCLUSION: Univariate pooling methods provide an estimate of test performance for an average disease spectrum which is possibly why results concur with the bivariate models. A better appreciation of such spectrum effects can be demonstrated through univariate analyses, especially when the forest plots are examined in either bias-adjusted or non-bias-adjusted univariate models.}, } @article {pmid25727712, year = {2015}, author = {Snow, PC and Sanger, DD and Belieu, K and Caire, LM and Eadie, PA}, title = {Snow et al.'s response to Richard Armstrong's Letter to the Editor.}, journal = {International journal of language & communication disorders}, volume = {50}, number = {4}, pages = {567-568}, doi = {10.1111/1460-6984.12163}, pmid = {25727712}, issn = {1460-6984}, mesh = {Child Health Services/*methods ; Female ; Humans ; *Language Disorders ; Male ; Speech-Language Pathology/*methods ; }, } @article {pmid25709144, year = {2014}, author = {Rubin, KH and Barstead, MG}, title = {Gender Differences in Child and Adolescent Social Withdrawal: A Commentary.}, journal = {Sex roles}, volume = {70}, number = {7-8}, pages = {274-284}, pmid = {25709144}, issn = {0360-0025}, support = {R01 MH058116/MH/NIMH NIH HHS/United States ; T32 HD007542/HD/NICHD NIH HHS/United States ; }, abstract = {In a manuscript entitled, "Bashful boys and coy girls: A review of gender differences in childhood shyness" Doey et al. (2013) suggest that shyness and its related constructs pose a greater developmental risk for boys compared to girls. They support this claim by citing empirical evidence suggesting that shy and anxiously withdrawn boys are responded to more negatively by important others (i.e., parents, peers, and teachers) and that the relationship between internalizing problems and anxious withdrawal is stronger for boys compared to girls. The principal aim of our commentary is to provide a critical examination of Doey et al.'s conclusions vis-à-vis gender differences in child and adolescent shyness. In this response, we begin by providing important theoretical background regarding shyness and its related constructs. Next, we critically examine the two main arguments the authors use in support of their conclusion through a review of existing empirical and theoretical work as well as the presentation of data from The Friendship Project. These data were analyzed with the specific purpose of providing an empirical test of the hypotheses implicit in Doey et al.'s primary arguments: 1) shy and anxiously withdrawn boys are responded to more negatively than girls and 2) the association between anxious withdrawal and internalizing problems is stronger for boys compared to girls. Our results indicate mixed support for these two claims. Finally, we conclude by suggesting new directions for future researchers interested in clarifying the relationship between gender and both the correlates and outcomes of childhood shyness.}, } @article {pmid25708547, year = {2015}, author = {Reisenzein, R}, title = {On the universality of the attribution-affect model of helping.}, journal = {International journal of psychology : Journal international de psychologie}, volume = {50}, number = {4}, pages = {308-311}, doi = {10.1002/ijop.12153}, pmid = {25708547}, issn = {1464-066X}, mesh = {Cross-Cultural Comparison ; Female ; *Helping Behavior ; Humans ; *Psychological Theory ; *Reproducibility of Results ; Social Responsibility ; }, abstract = {Although Pilati et al.'s (2014) findings question the strong quantitative universality of the attribution-affect model of helping, they are consistent with a weak form of quantitative universality, as well as with the qualitative universality of the theory. However, universality is put into question by previous studies revealing significant and sizeable between-study differences in the strength of the causal paths postulated by the theory. These differences may in part reflect differences in the type of helping situations studied.}, } @article {pmid25698986, year = {2015}, author = {Smith, TJ}, title = {The role of audience participation and task relevance on change detection during a card trick.}, journal = {Frontiers in psychology}, volume = {6}, number = {}, pages = {13}, pmid = {25698986}, issn = {1664-1078}, abstract = {Magicians utilize many techniques for misdirecting audience attention away from the secret sleight of a trick. One technique is to ask an audience member to participate in a trick either physically by asking them to choose a card or cognitively by having them keep track of a card. While such audience participation is an established part of most magic the cognitive mechanisms by which it operates are unknown. Failure to detect changes to objects while passively viewing magic tricks has been shown to be conditional on the changing feature being irrelevant to the current task. How change blindness operates during interactive tasks is unclear but preliminary evidence suggests that relevance of the changing feature may also play a role (Triesch et al., 2003). The present study created a simple on-line card trick inspired by Triesch et al.'s (2003) that allowed playing cards to be instantaneously replaced without distraction or occlusion as participants were either actively sorting the cards (Doing condition) or watching another person perform the task (Watching conditions). Participants were given one of three sets of instructions. The relevance of the card color to the task increased across the three instructions. During half of the trials a card changed color (but retained its number) as it was moving to the stack. Participants were instructed to immediately report such changes. Analysis of the probability of reporting a change revealed that actively performing the sorting task led to more missed changes than passively watching the same task but only when the changing feature was irrelevant to the sorting task. If the feature was relevant during either the pick-up or put-down action change detection was as good as during the watching block. These results confirm the ability of audience participation to create subtle dynamics of attention and perception during a magic trick and hide otherwise striking changes at the center of attention.}, } @article {pmid25693679, year = {2016}, author = {Barragán, A and Yamada, AM and Lee, KK and Barrio, C}, title = {Correlates in the Endorsement of Psychotic Symptoms and Services Use: Findings from the Collaborative Psychiatric Epidemiology Surveys.}, journal = {Community mental health journal}, volume = {52}, number = {6}, pages = {631-642}, pmid = {25693679}, issn = {1573-2789}, mesh = {Adolescent ; Adult ; Female ; Health Surveys ; Humans ; Male ; Mental Health Services/*statistics & numerical data ; Middle Aged ; Patient Acceptance of Health Care/psychology ; Psychotic Disorders/diagnosis/*psychology/therapy ; Social Support ; Young Adult ; }, abstract = {Endorsement of psychotic symptoms serves as an indicator of significant health issues and interpersonal distress. Seeking services is the ultimate recourse for many individuals, yet few studies have assessed the help-seeking process in a nationally representative sample. This study, guided by Lewis-Fernández et al.'s (J Nerv Ment Dis 197(5):337-347, 2009) analyses, examined the association of lifetime endorsement of psychotic symptoms with demographic, clinical and support system variables and types of services received. Based on nationally weighted epidemiological data, 11.6 % of adults reported one or more psychotic symptoms. Psychotic symptoms were associated with poor physical and mental health, specifically depressive, anxiety, and substance use disorders. Respondents were more likely to receive services from both informal and mental health providers and were more likely to be hospitalized than those not endorsing psychotic symptoms. Study findings inform community efforts to develop comprehensive services for individuals experiencing psychotic symptoms.}, } @article {pmid25688906, year = {2015}, author = {Vanden Bosch der Nederlanden, CM and Hannon, EE and Snyder, JS}, title = {Everyday musical experience is sufficient to perceive the speech-to-song illusion.}, journal = {Journal of experimental psychology. General}, volume = {144}, number = {2}, pages = {e43-9}, doi = {10.1037/xge0000056}, pmid = {25688906}, issn = {1939-2222}, mesh = {Adolescent ; Adult ; Auditory Perception/*physiology ; Female ; Humans ; Illusions/*psychology ; Male ; Middle Aged ; Music/*psychology ; Pitch Perception/physiology ; *Speech ; Young Adult ; }, abstract = {Speech and song are readily differentiated from each other in everyday communication, yet sometimes listeners who have formal music training will hear a spoken utterance transform from speech to song when it is repeated (Deutsch, Henthorn, & Lapidis, 2011). It remains unclear whether music training is required to perceive this illusory transformation or whether implicit knowledge of musical structure is sufficient. The current study replicates Deutsch et al.'s findings with musicians and demonstrates the generalizability of this auditory illusion to casual music listeners with no formal training. We confirm that the illusory transformation is disrupted when the pitch height of each repetition of the utterance is transposed, and we find that raising the pitch height has a different effect on listeners' ratings than does lowering it. Auditory illusions such as this may offer unique opportunities to compare domain-specific and domain-general processing in the brain while holding acoustic characteristics constant.}, } @article {pmid25688425, year = {2015}, author = {}, title = {"Psychophysiologic reactivity, subjective distress, and their associations with PTSD diagnosis": Correction to Pineles et al. (2013).}, journal = {Journal of abnormal psychology}, volume = {124}, number = {2}, pages = {287}, doi = {10.1037/abn0000054}, pmid = {25688425}, issn = {1939-1846}, abstract = {Reports an error in "Psychophysiologic reactivity, subjective distress, and their associations with PTSD diagnosis" by Suzanne L. Pineles, Michael K. Suvak, Gabrielle I. Liverant, Kristin Gregor, Blair E. Wisco, Roger K. Pitman and Scott P. Orr (Journal of Abnormal Psychology, 2013[Aug], Vol 122[3], 635-644). In Table 1 the sample of participants included in Orr et al.'s (1998) paper was incorrectly described as 100% male, rather than 100% female.}, } @article {pmid25681962, year = {2015}, author = {Trujols, J and Ballesteros, J and Solà, I and Portella, MJ}, title = {Improving systematic reviews on psychometric properties of measurement instruments: a letter to the Editor commenting on Reilly et al.'s (2015) review of the psychometric literature on QIDS.}, journal = {Journal of psychiatric research}, volume = {62}, number = {}, pages = {136-137}, doi = {10.1016/j.jpsychires.2015.01.013}, pmid = {25681962}, issn = {1879-1379}, mesh = {Depressive Disorder/*diagnosis/*psychology ; Female ; Humans ; Male ; Personality Assessment/*standards ; Psychiatric Status Rating Scales/*standards ; Psychometrics/*standards ; Self Report/*standards ; *Systematic Reviews as Topic ; }, } @article {pmid25681101, year = {2015}, author = {Lu, Y and Li, L and Peng, H and Yang, Y}, title = {An enhanced biometric-based authentication scheme for telecare medicine information systems using elliptic curve cryptosystem.}, journal = {Journal of medical systems}, volume = {39}, number = {3}, pages = {32}, pmid = {25681101}, issn = {1573-689X}, mesh = {Algorithms ; *Biometry ; Computer Security/*instrumentation ; Confidentiality ; Humans ; Information Systems/*organization & administration/standards ; Telemedicine/*organization & administration/standards ; }, abstract = {The telecare medical information systems (TMISs) enable patients to conveniently enjoy telecare services at home. The protection of patient's privacy is a key issue due to the openness of communication environment. Authentication as a typical approach is adopted to guarantee confidential and authorized interaction between the patient and remote server. In order to achieve the goals, numerous remote authentication schemes based on cryptography have been presented. Recently, Arshad et al. (J Med Syst 38(12): 2014) presented a secure and efficient three-factor authenticated key exchange scheme to remedy the weaknesses of Tan et al.'s scheme (J Med Syst 38(3): 2014). In this paper, we found that once a successful off-line password attack that results in an adversary could impersonate any user of the system in Arshad et al.'s scheme. In order to thwart these security attacks, an enhanced biometric and smart card based remote authentication scheme for TMISs is proposed. In addition, the BAN logic is applied to demonstrate the completeness of the enhanced scheme. Security and performance analyses show that our enhanced scheme satisfies more security properties and less computational cost compared with previously proposed schemes.}, } @article {pmid25670631, year = {2015}, author = {Hone, LS and Hurwitz, W and Lieberman, D}, title = {Sex differences in preferences for humor: a replication, modification, and extension.}, journal = {Evolutionary psychology : an international journal of evolutionary approaches to psychology and behavior}, volume = {13}, number = {1}, pages = {167-181}, pmid = {25670631}, issn = {1474-7049}, mesh = {Adolescent ; Adult ; Choice Behavior/*physiology ; Female ; Humans ; *Interpersonal Relations ; Male ; Sex Factors ; Wit and Humor as Topic/*psychology ; Young Adult ; }, abstract = {Evolutionary-minded scientists have proposed that humor is a sexually selected trait in men that signals mate quality. Indeed, women tend to prefer men who make them laugh and men tend to prefer women who laugh at their jokes. However, it is unclear how robust this pattern is. Here we report a replication of one of the first studies (Bressler, Martin, and Balshine, 2006) to examine the sex differences in preferences for humor receptivity versus humor production. We replicate Bressler et al.'s (2006) findings that men prefer women who are receptive to their humor whereas women prefer men who produce humor. These findings held even after we modified Bressler et al.'s questionnaire for better conceptual validity. Furthermore, using a separate measure designed to assess trade-offs, we found that men viewed humor receptivity as a necessity and humor production as a luxury when they were asked to create an ideal long-term partner. For women, it was just the opposite. These results bolster the claim that sexual selection has shaped sex differences regarding preferences for a prospective mate's sense of humor and that what one means by "sense of humor" can vary.}, } @article {pmid25666924, year = {2015}, author = {Das, AK}, title = {A secure and robust password-based remote user authentication scheme using smart cards for the integrated EPR information system.}, journal = {Journal of medical systems}, volume = {39}, number = {3}, pages = {25}, pmid = {25666924}, issn = {1573-689X}, mesh = {Computer Security/*instrumentation ; Confidentiality ; Electronic Health Records/*organization & administration/standards ; Humans ; Information Systems/*organization & administration/standards ; User-Computer Interface ; }, abstract = {An integrated EPR (Electronic Patient Record) information system of all the patients provides the medical institutions and the academia with most of the patients' information in details for them to make corrective decisions and clinical decisions in order to maintain and analyze patients' health. In such system, the illegal access must be restricted and the information from theft during transmission over the insecure Internet must be prevented. Lee et al. proposed an efficient password-based remote user authentication scheme using smart card for the integrated EPR information system. Their scheme is very efficient due to usage of one-way hash function and bitwise exclusive-or (XOR) operations. However, in this paper, we show that though their scheme is very efficient, their scheme has three security weaknesses such as (1) it has design flaws in password change phase, (2) it fails to protect privileged insider attack and (3) it lacks the formal security verification. We also find that another recently proposed Wen's scheme has the same security drawbacks as in Lee at al.'s scheme. In order to remedy these security weaknesses found in Lee et al.'s scheme and Wen's scheme, we propose a secure and efficient password-based remote user authentication scheme using smart cards for the integrated EPR information system. We show that our scheme is also efficient as compared to Lee et al.'s scheme and Wen's scheme as our scheme only uses one-way hash function and bitwise exclusive-or (XOR) operations. Through the security analysis, we show that our scheme is secure against possible known attacks. Furthermore, we simulate our scheme for the formal security verification using the widely-accepted AVISPA (Automated Validation of Internet Security Protocols and Applications) tool and show that our scheme is secure against passive and active attacks.}, } @article {pmid25666493, year = {2015}, author = {Kaplan, JM and Pigliucci, M and Banta, JA}, title = {Gould on Morton, Redux: What can the debate reveal about the limits of data?.}, journal = {Studies in history and philosophy of biological and biomedical sciences}, volume = {52}, number = {}, pages = {22-31}, doi = {10.1016/j.shpsc.2015.01.001}, pmid = {25666493}, issn = {1879-2499}, mesh = {Humans ; *Philosophy ; *Racial Groups ; Skull/*anatomy & histology ; }, abstract = {Lewis et al. (2011) attempted to restore the reputation of Samuel George Morton, a 19th century physician who reported on the skull sizes of different folk-races. Whereas Gould (1978) claimed that Morton's conclusions were invalid because they reflected unconscious bias, Lewis et al. alleged that Morton's findings were, in fact, supported, and Gould's analysis biased. We take strong exception to Lewis et al.'s thesis that Morton was "right." We maintain that Gould was right to reject Morton's analysis as inappropriate and misleading, but wrong to believe that a more appropriate analysis was available. Lewis et al. fail to recognize that there is, given the dataset available, no appropriate way to answer any of the plausibly interesting questions about the "populations" in question (which in many cases are not populations in any biologically meaningful sense). We challenge the premise shared by both Gould and Lewis et al. that Morton's confused data can be used to draw any meaningful conclusions. This, we argue, reveals the importance of properly focusing on the questions asked, rather than more narrowly on the data gathered.}, } @article {pmid25665629, year = {2015}, author = {Roff, S}, title = {Reconsidering the "decline" of medical student empathy as reported in studies using the Jefferson Scale of Physician Empathy-Student version (JSPE-S).}, journal = {Medical teacher}, volume = {37}, number = {8}, pages = {783-786}, doi = {10.3109/0142159X.2015.1009022}, pmid = {25665629}, issn = {1466-187X}, abstract = {INTRODUCTION: The suggestion that empathy "declines" or "erodes" as students progress through medical school has largely rested on observations reported from Jefferson Medical College in the United States using the Jefferson Scale of Physician Empathy (JSPE) developed by Hojat and colleagues. Now that the student version of JSPE has been administered to medical students in more than a dozen countries, it is timely to consider whether or not the Jefferson "case study" and the conclusions drawn from it are generalisable.

METHODS: A literature research was conducted on MEDLINE in mid-2014 to identify studies reporting administrations of the Student version of JPSE (JSPE-S) to cohorts of medical students and the means for studies and their sub-parts conducted in Japan, South Korea, China, Kuwait, India, Iran, UK, USA, Australia, Brazil, Colombia, the Dominican Republic and Portugal.

RESULTS: The means of these studies from a dozen countries outside the USA consistently cluster round 75% out of the possible maximum of 140 unlike the early Jefferson studies (although the later Jefferson means are also <120).

CONCLUSIONS: These observations may support Costa et al.'s contention that "a latent growth model suggests that empathy of medical students does not decline over time" (p. 509) - or at least not significantly. But in order to understand the maturation process of medical students and trainees we need to develop more sophisticated, integrated models that combine culturally-sensitive concepts of emotional intelligence and moral reasoning with far more refined understandings of the nature of empathy required for the safe practice of patient-centred medicine.}, } @article {pmid25665075, year = {2015}, author = {Walters, GD and DeLisi, M}, title = {Psychopathy and violence: Does antisocial cognition mediate the relationship between the PCL: YV factor scores and violent offending?.}, journal = {Law and human behavior}, volume = {39}, number = {4}, pages = {350-359}, doi = {10.1037/lhb0000123}, pmid = {25665075}, issn = {1573-661X}, mesh = {Adolescent ; Antisocial Personality Disorder/*psychology ; Female ; Humans ; *Juvenile Delinquency ; Male ; *Personality Assessment ; *Violence ; }, abstract = {The purpose of this study was to determine whether proactive and reactive antisocial cognition mediate the effect of Factors 1 (core personality features) and 2 (behavioral deviance) of the Psychopathy Checklist: Youth Version (PCL: YV; Forth, Kosson, & Hare, 2003) on violent offending. In this study Bandura et al.'s (1996) Moral Disengagement (MD) scale and the Impulse Control (IC) scale of the Weinberger Adjustment Inventory (WAI; Weinberger & Schwartz, 1990) served as proxies for proactive and reactive antisocial cognition, respectively. It was hypothesized that proactive antisocial cognition (MD) would mediate the Factor 1-violence relationship and that both proactive antisocial cognition and reactive antisocial cognition (IC) would mediate the Factor 2-violence relationship. A 3-wave path analysis of data from 1,354 adjudicated delinquents produced results consistent with the first part of the hypothesis (i.e., proactive antisocial mediation of the Factor 1-violence relationship) but inconsistent with the second part of the hypothesis (i.e., only proactive antisocial cognition mediated the Factor 2-violence relationship). Whereas the direct path from Factor 1 to violent offending was no longer significant when MD and IC were taken into account, the direct path from Factor 2 to violent offender remained significant even after MD and IC were included as mediators. This suggests that whereas proactive antisocial cognition plays a major role in mediating the Factor 1-violence relationship, the Factor 2-violence relationship is mediated by proactive antisocial cognition and variables not included or not adequately covered in the current study.}, } @article {pmid25664953, year = {2015}, author = {}, title = {On the association between loneliness and physical warmth-seeking through bathing: Reply to Donnellan et al. (2014) and three further replications of Bargh and Shalev (2012) study 1: Correction to Shalev and Bargh (2014).}, journal = {Emotion (Washington, D.C.)}, volume = {15}, number = {1}, pages = {123}, doi = {10.1037/emo0000046}, pmid = {25664953}, issn = {1931-1516}, abstract = {Reports an error in "On the Association Between Loneliness and Physical Warmth-Seeking Through Bathing: Reply to Donnellan et al. (2014) and Three Further Replications of Bargh and Shalev (2012) Study 1" by Idit Shalev and John Bargh (Emotion, Advanced Online Publication, Sep 8, 2014, np). In the article, there was an error in the abstract. The name of author Donnellan was misspelled as Donellan. (The following abstract of the original article appeared in record 2014-37463-001.) [Correction Notice: An Erratum for this article was reported in Vol 15(1) of Emotion (see record 2015-05076-004). In the article, the wrong supplemental file was originally posted. The correct file has now been posted.] As Tversky and Kahneman (1971) noted, effect sizes in smaller samples are inherently unstable. Donellan et al. (2014) in a large sample show that the relation between trait loneliness and warmth extraction through bathing activities is much smaller than in our initial smaller samples. We report further replications of our original findings in samples from India, Israel, and North America, again showing significant correlations between loneliness and physical warmth extraction from bathing and showering; the overall effect being reliable across all three samples, although, consistent with Donellan et al.'s conclusions, smaller than in our original studies. We also respond to criticisms of the original data analyses, noting that removal of the problematic 'bathing frequency' item from the warmth index did not substantially change the results and thus our conclusions from them. We also note that in their 2 studies in which Donellan et al. attempted to most closely follow our original procedure, they did replicate our original results, but not in the other 7 studies in which considerable procedural changes were made. As our new replications reveal variability in bathing and showering preferences and habits around the world, we recommend the inclusion of a wider sample of cultures beyond North American in future research. This research should also focus not only on the narrower question of how loneliness relates to bathing activities but on the broader relation between feelings of social coldness (e.g., after rejection or exclusion) and the seeking of physical warmth (e.g., warm food and drink, thermostat settings). (PsycINFO Database Record (c) 2015 APA, all rights reserved).}, } @article {pmid25664952, year = {2015}, author = {}, title = {On the association between loneliness and physical warmth-seeking through bathing: Reply to Donnellan et al. (2014) and three further replications of Bargh and Shalev (2012) study 1: Correction to Shalev and Bargh (2014).}, journal = {Emotion (Washington, D.C.)}, volume = {15}, number = {1}, pages = {72}, doi = {10.1037/emo0000031}, pmid = {25664952}, issn = {1931-1516}, abstract = {Reports an error in "On the Association Between Loneliness and Physical Warmth-Seeking Through Bathing: Reply to Donnellan et al. (2014) and Three Further Replications of Bargh and Shalev (2012) Study 1" by Idit Shalev and John Bargh (Emotion, Advanced Online Publication, Sep 8, 2014, np). In the article, the wrong supplemental file was originally posted. The correct file has now been posted. (The following abstract of the original article appeared in record 2014-37463-001.) As Tversky and Kahneman (1971) noted, effect sizes in smaller samples are inherently unstable. Donellan et al. (2014) in a large sample show that the relation between trait loneliness and warmth extraction through bathing activities is much smaller than in our initial smaller samples. We report further replications of our original findings in samples from India, Israel, and North America, again showing significant correlations between loneliness and physical warmth extraction from bathing and showering; the overall effect being reliable across all three samples, although, consistent with Donellan et al.'s conclusions, smaller than in our original studies. We also respond to criticisms of the original data analyses, noting that removal of the problematic 'bathing frequency' item from the warmth index did not substantially change the results and thus our conclusions from them. We also note that in their 2 studies in which Donellan et al. attempted to most closely follow our original procedure, they did replicate our original results, but not in the other 7 studies in which considerable procedural changes were made. As our new replications reveal variability in bathing and showering preferences and habits around the world, we recommend the inclusion of a wider sample of cultures beyond North American in future research. This research should also focus not only on the narrower question of how loneliness relates to bathing activities but on the broader relation between feelings of social coldness (e.g., after rejection or exclusion) and the seeking of physical warmth (e.g., warm food and drink, thermostat settings). (PsycINFO Database Record (c) 2015 APA, all rights reserved).}, } @article {pmid25663481, year = {2015}, author = {Guo, D and Wen, Q and Li, W and Zhang, H and Jin, Z}, title = {An improved biometrics-based authentication scheme for telecare medical information systems.}, journal = {Journal of medical systems}, volume = {39}, number = {3}, pages = {20}, pmid = {25663481}, issn = {1573-689X}, mesh = {Algorithms ; *Biometry ; Computer Security/*instrumentation ; Confidentiality ; Humans ; Information Systems/*organization & administration/standards ; Telemedicine/*organization & administration/standards ; }, abstract = {Telecare medical information system (TMIS) offers healthcare delivery services and patients can acquire their desired medical services conveniently through public networks. The protection of patients' privacy and data confidentiality are significant. Very recently, Mishra et al. proposed a biometrics-based authentication scheme for telecare medical information system. Their scheme can protect user privacy and is believed to resist a range of network attacks. In this paper, we analyze Mishra et al.'s scheme and identify that their scheme is insecure to against known session key attack and impersonation attack. Thereby, we present a modified biometrics-based authentication scheme for TMIS to eliminate the aforementioned faults. Besides, we demonstrate the completeness of the proposed scheme through BAN-logic. Compared to the related schemes, our protocol can provide stronger security and it is more practical.}, } @article {pmid25656552, year = {2017}, author = {Austin, PC and Pencinca, MJ and Steyerberg, EW}, title = {Predictive accuracy of novel risk factors and markers: A simulation study of the sensitivity of different performance measures for the Cox proportional hazards regression model.}, journal = {Statistical methods in medical research}, volume = {26}, number = {3}, pages = {1053-1077}, pmid = {25656552}, issn = {1477-0334}, mesh = {Age Factors ; Biomarkers ; Heart Failure/mortality ; Humans ; Monte Carlo Method ; *Proportional Hazards Models ; Risk Factors ; }, abstract = {Predicting outcomes that occur over time is important in clinical, population health, and health services research. We compared changes in different measures of performance when a novel risk factor or marker was added to an existing Cox proportional hazards regression model. We performed Monte Carlo simulations for common measures of performance: concordance indices (c, including various extensions to survival outcomes), Royston's D index, R[2]-type measures, and Chambless' adaptation of the integrated discrimination improvement to survival outcomes. We found that the increase in performance due to the inclusion of a risk factor tended to decrease as the performance of the reference model increased. Moreover, the increase in performance increased as the hazard ratio or the prevalence of a binary risk factor increased. Finally, for the concordance indices and R[2]-type measures, the absolute increase in predictive accuracy due to the inclusion of a risk factor was greater when the observed event rate was higher (low censoring). Amongst the different concordance indices, Chambless and Diao's c-statistic exhibited the greatest increase in predictive accuracy when a novel risk factor was added to an existing model. Amongst the different R[2]-type measures, O'Quigley et al.'s modification of Nagelkerke's R[2] index and Kent and O'Quigley's [Formula: see text] displayed the greatest sensitivity to the addition of a novel risk factor or marker. These methods were then applied to a cohort of 8635 patients hospitalized with heart failure to examine the added benefit of a point-based scoring system for predicting mortality after initial adjustment with patient age alone.}, } @article {pmid25651950, year = {2015}, author = {Mishra, D}, title = {Understanding security failures of two authentication and key agreement schemes for telecare medicine information systems.}, journal = {Journal of medical systems}, volume = {39}, number = {3}, pages = {19}, pmid = {25651950}, issn = {1573-689X}, mesh = {Algorithms ; Computer Security/*instrumentation ; Confidentiality ; Humans ; Information Systems/*organization & administration/standards ; Nonlinear Dynamics ; Telemedicine/*organization & administration/standards ; }, abstract = {Smart card based authentication and key agreement schemes for telecare medicine information systems (TMIS) enable doctors, nurses, patients and health visitors to use smart cards for secure login to medical information systems. In recent years, several authentication and key agreement schemes have been proposed to present secure and efficient solution for TMIS. Most of the existing authentication schemes for TMIS have either higher computation overhead or are vulnerable to attacks. To reduce the computational overhead and enhance the security, Lee recently proposed an authentication and key agreement scheme using chaotic maps for TMIS. Xu et al. also proposed a password based authentication and key agreement scheme for TMIS using elliptic curve cryptography. Both the schemes provide better efficiency from the conventional public key cryptography based schemes. These schemes are important as they present an efficient solution for TMIS. We analyze the security of both Lee's scheme and Xu et al.'s schemes. Unfortunately, we identify that both the schemes are vulnerable to denial of service attack. To understand the security failures of these cryptographic schemes which are the key of patching existing schemes and designing future schemes, we demonstrate the security loopholes of Lee's scheme and Xu et al.'s scheme in this paper.}, } @article {pmid25650142, year = {2015}, author = {Haytoglu, S and Haytoglu, TG and Bayar Muluk, N and Kuran, G and Arikan, OK}, title = {Comparison of two incisionless otoplasty techniques for prominent ears in children.}, journal = {International journal of pediatric otorhinolaryngology}, volume = {79}, number = {4}, pages = {504-510}, doi = {10.1016/j.ijporl.2015.01.014}, pmid = {25650142}, issn = {1872-8464}, mesh = {Adolescent ; Child ; Child, Preschool ; Ear Auricle/*abnormalities/*surgery ; Ear Cartilage/pathology/*surgery ; Female ; Follow-Up Studies ; Humans ; Male ; Operative Time ; Patient Satisfaction ; Prospective Studies ; Plastic Surgery Procedures/*methods ; *Suture Techniques ; Treatment Outcome ; }, abstract = {OBJECTIVES: In the present study, we applied two incisionless suture techniques for otoplasty: Haytoglu et al.'s modification of incisionless otoplasty technique and Fritsch's incisionless otoplasty technique for correction of prominent ears.

METHODS: In this prospective study, 60 patients with prominent ears were included in the study. In Group 1, 55 ears of 30 patients (25 bilateral and 5 unilateral) were operated with Haytoglu et al.'s modification of incisionless otoplasty technique. In Group 2, 57 ears of 30 patients (27 bilateral and 3 unilateral) were operated with Fritsch's incisionless otoplasty technique. For comparison of two methods, auriculocephalic distances were measured at three levels which were level 1 (the most superior point of the auricle), level 2 (the midpoint of the auricle) and level 3 (level of the lobule) pre-operatively (preop); and measurements were repeated at the end of the surgery (PO(0-day)), 1st month (PO(1-Mo)) and 6th month (PO(6-Mo)) after the surgery, in both groups. Patient satisfaction was evaluated using a visual analog scale (VAS). Moreover, Global Aesthetic Improvement Scale (GAIS) was rated by an independent, non-participating plastic surgeon at 6 months after the surgery.

RESULTS: Operation time was 15.9±5.6min in Group 1 (Haytoglu et al.'s) and 19±4.7min in Group 2 (Fritsch). Hematoma, infection, bleeding, keloid scar formation, sharp edges or irregularities of the cartilage were not observed in any group. Suture extrusion was detected in 14.03% of Group 1 and 16.1% of Group 2. No statistically significant difference was observed between auriculocephalic distances at levels 1-3 of groups at preop, PO(0-day), PO(1-Mo) and PO(6-Mo) separately. Similarly, difference in auriculocephalic distances (preop values-PO(6-Mo) values) was not detected as statistically significant in Groups 1 and 2 at three levels. In both techniques, No statistically significant difference was observed in patient satisfaction at 6th months after the operation which was measured using Visual Analogue Scale (VAS) on 0 to 100 scales. According to GAIS, the patients were rated as 92.9% "improved" and 7.1% "no change" in Group 1; as 94.6% "improved" and 5.4% "no change" in Group 2.

CONCLUSIONS: Due to the similar results, Haytoglu et al.'s and Fritsch's incisionless otoplasty techniques are good options in the treatment of prominent ears, especially in pediatric patients with isolated inadequate development of antihelical ridge, and with soft auricular cartilage.}, } @article {pmid25649070, year = {2016}, author = {Lancaster, C}, title = {The Acid Test for Biological Science: STAP Cells, Trust, and Replication.}, journal = {Science and engineering ethics}, volume = {22}, number = {1}, pages = {147-167}, pmid = {25649070}, issn = {1471-5546}, mesh = {Animals ; Biological Science Disciplines/*ethics ; Biomedical Research/*ethics ; Ethics, Research ; Humans ; Japan ; Mice ; *Pluripotent Stem Cells ; Publishing/*ethics ; *Reproducibility of Results ; Research Personnel ; Science/ethics ; *Scientific Misconduct ; *Trust ; }, abstract = {In January 2014, a letter and original research article were published in Nature describing a process whereby somatic mouse cells could be converted into stem cells by subjecting them to stress. These "stimulus-triggered acquisition of pluripotency" (STAP) cells were shown to be capable of contributing to all cell types of a developing embryo, and extra-embryonic tissues. The lead author of the publications, Haruko Obokata, became an overnight celebrity in Japan, where she was dubbed the new face of Japanese science. However, in the weeks that followed publication of the research, issues arose. Other laboratories and researchers (including authors on the original papers) found that they were unable to replicate Obokata et al.'s work. Closer scrutiny of the papers by the scientific community also suggested that there was manipulation of images that had been published, and Obokata was accused of misconduct. Those who should have been supervising her work (also her co-authors on the publications) were also heavily criticised. The STAP cell saga of 2014 is used as an example to highlight the importance of trust and replication in twenty-first century biological science. The role of trust in the scientific community is highlighted, and the effects on interactions between science and the public examined. Similarly, this essay aims to highlight the importance of replication, and how this is understood by researchers, the media, and the public. The expected behaviour of scientists in the twenty-first century is now more closely scrutinised.}, } @article {pmid25625433, year = {2015}, author = {Chiou, GJ and Crowe, C and McGoldrick, R and Hui, K and Pham, H and Chang, J}, title = {Optimization of an injectable tendon hydrogel: the effects of platelet-rich plasma and adipose-derived stem cells on tendon healing in vivo.}, journal = {Tissue engineering. Part A}, volume = {21}, number = {9-10}, pages = {1579-1586}, doi = {10.1089/ten.TEA.2014.0490}, pmid = {25625433}, issn = {1937-335X}, support = {I01 RX001458/RX/RRD VA/United States ; }, mesh = {Adipose Tissue/*cytology ; Animals ; Biomechanical Phenomena/drug effects ; Elastic Modulus/drug effects ; Humans ; Hydrogel, Polyethylene Glycol Dimethacrylate/*pharmacology ; Imaging, Three-Dimensional ; Injections ; Luminescent Measurements ; Platelet-Rich Plasma/*metabolism ; Rats, Wistar ; Staining and Labeling ; *Stem Cell Transplantation ; Stem Cells/*cytology/drug effects/metabolism ; Tendon Injuries/pathology/physiopathology/therapy ; Tendons/drug effects/*pathology/physiopathology ; Weight-Bearing ; Wound Healing/*drug effects ; }, abstract = {INTRODUCTION: Acute and chronic tendon injuries would benefit from stronger and more expeditious healing. We hypothesize that supplementation of a biocompatible tendon hydrogel with platelet-rich plasma (PRP) and adipose-derived stem cells (ASCs) would augment the tendon healing process.

MATERIALS AND METHODS: Using 55 Wistar rats, a full-thickness defect was created within the midsubstance of each Achilles tendon with the addition of one of five experimental conditions: (i) saline control (50-μL), (ii) tendon hydrogel (50-μL), (iii) tendon hydrogel (45-μL)+PRP (5-μL), (iv) tendon hydrogel (45-μL)+2×10(6)-ASCs/mL in phosphate buffered saline (5-μL), and (v) tendon hydrogel (45-μL)+2×10(6)-ASCs/mL in PRP (5-μL). Hydrogel was developed from decellularized, human cadaveric tendons. Fresh rat PRP was obtained per Amable et al.'s technique, and green fluorescent protein/luciferase-positive rat ASCs were utilized. Rats were sacrificed at weeks 1, 2, 4, and 8 after injury. Real-time in vivo bioluminescence imaging of groups with ASCs was performed. Upon sacrifice, Achilles tendons underwent biomechanical and histological evaluation. Comparisons across groups were analyzed using the two-sample Z-test for proportions and the Student's t-test for independent samples. Significance was set at p<0.05.

RESULTS: (i) Bioluminescence imaging demonstrated that total photon flux was significantly increased for hydrogel+PRP+ASCs, versus hydrogel+ASCs for each postoperative day imaged (p<0.03). (ii) Mean ultimate failure load (UFL) was increased for hydrogel augmented with PRP and/or ASCs versus hydrogel alone at week 2 (p<0.03). By week 4, hydrogel alone reached a similar mean UFL to hydrogel augmented with PRP and/or ASCs (p>0.3). However, at week 8, hydrogel with PRP and ASCs demonstrated increased strength over other groups (p<0.05), except for hydrogel with PRP (p=0.25). (iii) Upon histological analysis, Hematoxylin and Eosin staining showed increased extracellular matrix formation in groups containing PRP and increased cellularity in groups containing ASCs. Groups containing both PRP and ASCs demonstrated both of these characteristics.

CONCLUSION: PRP and ASCs are easily accessible bioactive products that have potentiating effects on tendon hydrogel. Augmentation with these two factors encourages earlier mechanical strength and functional restoration. Thus, biochemically, tendon hydrogel augmented with PRP and/or ASCs, serves as a promising therapeutic modality for augmenting the tendon healing process after injury.}, } @article {pmid25622082, year = {2015}, author = {Rodríguez, SA and Roter, DL and Castillo-Salgado, C and Hooker, GW and Erby, LH}, title = {Translation and validation of a Spanish-language genetic health literacy screening tool.}, journal = {Health psychology : official journal of the Division of Health Psychology, American Psychological Association}, volume = {34}, number = {2}, pages = {120-129}, doi = {10.1037/hea0000162}, pmid = {25622082}, issn = {1930-7810}, support = {//Intramural NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Aged ; Comprehension ; Cross-Sectional Studies ; Female ; *Genetics ; *Health Literacy ; Hispanic or Latino/*psychology ; Humans ; *Language ; Male ; Maryland ; Middle Aged ; *Surveys and Questionnaires ; Young Adult ; }, abstract = {OBJECTIVE: Literacy deficits and underutilization of medical services have been linked to health disparities among minorities, and this appears especially relevant for the Latino population. Given the increasing importance of genetics, assessment of genetic health literacy may direct future efforts to better serve this vulnerable population. The current study was designed to contribute to this area by translating and validating a Spanish-language genetic health literacy measure.

METHOD: This was a cross-sectional study involving an interviewer-administered questionnaire. Eligible individuals were Latinos between the ages of 18 and 75 residing in Maryland, who self-reported Spanish as their primary language, recruited through convenience sampling. The genetic health literacy measure components were adapted from existing English-language measures [Erby, Roter, Larson, & Cho's (2008) Rapid Estimate of Adult Literacy in Genetics (REAL-G) and Hooker et al.'s (2014) Genetic Literacy and Comprehension]. An existing Spanish-language general health literacy measure was used to establish preliminary concurrent validity [Lee, Bender, Ruiz, & Cho's (2006) SAHLSA].

RESULTS: 116 individuals completed the assessment. The Spanish-language REAL-G (REAL-G-Sp) was found to correlate well with the SAHLSA (Pearson's r = .77, p < .01). A cut-off score of 59 (out of 62) distinguished low versus high genetic health literacy with a sensitivity of 86% and specificity of 71%, identifying 28% of participants as having inadequate genetic health literacy.

CONCLUSIONS: The REAL-G-Sp was found to have preliminary concurrent validity with an existing health literacy measure in the Latino population residing in Maryland. Significant proportions of this population are predicted to have limitations in genetic health literacy, even when information is provided in Spanish.}, } @article {pmid25618472, year = {2015}, author = {Carvalho, T and Cunha, M and Pinto-Gouveia, J and Duarte, J}, title = {Portuguese version of the PTSD Checklist-Military Version (PCL-M)-I: Confirmatory Factor Analysis and reliability.}, journal = {Psychiatry research}, volume = {226}, number = {1}, pages = {53-60}, doi = {10.1016/j.psychres.2014.11.055}, pmid = {25618472}, issn = {1872-7123}, mesh = {Aged ; Aged, 80 and over ; Checklist/methods/standards ; *Diagnostic and Statistical Manual of Mental Disorders ; Factor Analysis, Statistical ; Female ; Humans ; Male ; Middle Aged ; Portugal/epidemiology ; Reproducibility of Results ; Self Report/*standards ; Stress Disorders, Post-Traumatic/*diagnosis/epidemiology/*psychology ; Veterans/*psychology ; }, abstract = {The PTSD Checklist-Military Version (PCL-M) is a brief self-report instrument widely used to assess Post-traumatic Stress Disorder (PTSD) symptomatology in war Veterans, according to DSM-IV. This study sought out to explore the factor structure and reliability of the Portuguese version of the PCL-M. A sample of 660 Portuguese Colonial War Veterans completed the PCL-M. Several Confirmatory Factor Analyses were conducted to test different structures for PCL-M PTSD symptoms. Although the respecified first-order four-factor model based on King et al.'s model showed the best fit to the data, the respecified first and second-order models based on the DSM-IV symptom clusters also presented an acceptable fit. In addition, the PCL-M showed adequate reliability. The Portuguese version of the PCL-M is thus a valid and reliable measure to assess the severity of PTSD symptoms as described in DSM-IV. Its use with Portuguese Colonial War Veterans may ease screening of possible PTSD cases, promote more suitable treatment planning, and enable monitoring of therapeutic outcomes.}, } @article {pmid25614234, year = {2015}, author = {Martin, JA and Karnath, HO and Himmelbach, M}, title = {Revisiting the cortical system for peripheral reaching at the parieto-occipital junction.}, journal = {Cortex; a journal devoted to the study of the nervous system and behavior}, volume = {64}, number = {}, pages = {363-379}, doi = {10.1016/j.cortex.2014.11.012}, pmid = {25614234}, issn = {1973-8102}, mesh = {Adult ; Brain Mapping ; Eye Movements/physiology ; Female ; Functional Laterality/physiology ; Humans ; Magnetic Resonance Imaging ; Male ; Occipital Lobe/*physiology ; Parietal Lobe/*physiology ; Psychomotor Performance/*physiology ; Visual Fields/physiology ; Young Adult ; }, abstract = {Optic ataxia (OA) is a neurological disorder that is characterised by misreaching to targets in the visual periphery. The anatomy of OA thus provides important information for the neural representation of visually guided reaching in humans. In 2005 a lesion mapping analysis of OA localised the critical lesion site at the parieto-occipital junction (POJ) (Karnath & Perenin, 2005). This work was accompanied by the discovery of a peripheral reaching module at the POJ in an fMRI study (Prado et al., 2005). The ostensible overlap between the territory typically affected in patients with OA and the findings of Prado et al. (2005) had a tremendous influence on the search for a cortical peripheral reaching module. However, a close inspection of the functional Magnetic Resonance Imaging (fMRI) study revealed that a comparison between reaching towards visible targets in the peripheral visual field and reaching to visible targets in the central visual field--which is the key aspect in clinical examinations of OA--was not conducted. Moreover, whereas main effects of reaching overlapped with the OA lesion site, specific interaction effects did not overlap. We performed a direct comparison between reaching to visible peripheral targets and reaching to visible central targets to address the inconsistencies between the aforementioned studies. Our analysis shows that Prado et al.'s study cannot be taken as evidence for a delineated module for peripheral reaching. In contrast to Prado et al. we found a combined system of POJ, IPS and SPL areas--the posterior human 7A, mIPS, V6A and the posterior IPS--with increased signals during reaching to peripheral targets.}, } @article {pmid25613760, year = {2015}, author = {Scherzer, TR and Ekroll, V}, title = {Partial modal completion under occlusion: what do modal and amodal percepts represent?.}, journal = {Journal of vision}, volume = {15}, number = {1}, pages = {15.1.22}, doi = {10.1167/15.1.22}, pmid = {25613760}, issn = {1534-7362}, mesh = {Adult ; Depth Perception/*physiology ; Female ; Form Perception/*physiology ; Humans ; Male ; Optical Illusions/*physiology ; Perceptual Closure/*physiology ; }, abstract = {In the occlusion illusion, a partly occluded object is perceived as though it were less occluded than it actually is (Palmer, Brooks, & Lai, 2007). We confirm and extend this finding using a stimulus with a moving occluder. In agreement with Palmer et al.'s (2007) findings and their partial-modal-completion hypothesis, we found that the illusion is indeed related to the sensory evidence for occlusion. Our experiments also confirm their speculation that the occlusion illusion involves an intriguing, seemingly paradoxical percept. In our experiments, subjects viewed an opaque disk with an open sector rotating in front of a background and indicated the perceived angular extent (a) of the occluder and (b) of the part of the background experienced as directly visible through the open sector. While the former was judged quite accurately, the latter was clearly overestimated. Thus, the angular extent of the background experienced as occluded and the extent experienced as directly visible sum to more than 360°, which makes the total percept an impossible figure. We argue that the key to resolving this paradox is to question the seemingly self-evident assumption that occluded and unoccluded portions of a visual scene are represented by amodal and modal percepts, respectively. Instead, we propose that visual percepts are experienced as modal whenever they are based on sufficiently conclusive sensory evidence and are otherwise experienced as amodal. Functionally, this perceptual representation of the conclusiveness of the sensory evidence underlying perceptual inferences might be more useful than estimates about optical visibility.}, } @article {pmid25595548, year = {2015}, author = {Gocha, TP and Ingvoldstad, ME and Kolatorowicz, A and Cosgriff-Hernandez, MT and Sciulli, PW}, title = {Testing the applicability of six macroscopic skeletal aging techniques on a modern Southeast Asian sample.}, journal = {Forensic science international}, volume = {249}, number = {}, pages = {318.e1-7}, doi = {10.1016/j.forsciint.2014.12.015}, pmid = {25595548}, issn = {1872-6283}, mesh = {Adult ; Age Determination by Skeleton/*methods ; Aged ; *Asian People ; Bone and Bones/*anatomy & histology ; Female ; Forensic Anthropology ; Humans ; Male ; Middle Aged ; Thailand ; Young Adult ; }, abstract = {Most macroscopic skeletal aging techniques used by forensic anthropologists have been developed and tested only on reference material from western populations. This study examined the performance of six aging techniques on a known age sample of 88 Southeast Asian individuals. Methods examined included the Suchey-Brooks method of aging the symphyseal face of the os pubis (Brooks and Suchey, Hum. Evol. 5 (1990) 227), Buckberry and Chamberlain's, Am. J. Phys. Anthropol. 119 (2002) 231 and Osborne et al.'s, J. Forensic Sci. 49 (2004) 1 revisions of the Lovejoy et al., Am. J. Phys. Anthropol. 68 (1985) 15 method of aging the auricular surface of the ilium, İşcan et al.'s, J. Forensic Sci. 29 (1984) 1094, İşcan et al.'s, J. Forensic Sci. 30 (1985) 853 method of aging the sternal end of the fourth rib, and Meindl and Lovejoy's, Am. J. Phys. Anthropol. 68 (1985) 57 methods for aging both lateral-anterior and vault sutures on the cranium. The results of this study indicate that application of aging techniques commonly used in forensic anthropology to individuals identified as Asian, and more specifically Southeast Asian, should not be undertaken injudiciously. Of the six individual methods tested here, the Suchey-Brooks pubic symphysis aging method performs best, though average age estimates were still off by nearly 10 years or greater. Methods for aging the auricular surface perform next best, though the Osborne et al. method works better for individuals below 50 years and the Buckberry and Chamberlain method works better for those above 50 years. Methods for age estimation from the sternal ends of the fourth rib and vault and lateral-anterior cranial sutures perform poorly and are not recommended for use on remains of Southeast Asian ancestry. Combining age estimates from multiple indicators, specifically the pubic symphysis and one auricular surface method, was superior to individual methods. Data and a worked example are provided for calculating the conditional probability that an individual belongs to a particular age decade, though overall age estimates may still be broad.}, } @article {pmid25592217, year = {2015}, author = {Nieuwoudt, JE}, title = {Commentary on: Muscle dysmorphia: could it be classified as an addiction to body image?.}, journal = {Journal of behavioral addictions}, volume = {4}, number = {1}, pages = {8-10}, pmid = {25592217}, issn = {2063-5303}, mesh = {Behavior, Addictive/*psychology ; Body Dysmorphic Disorders/*classification/*psychology ; Body Image/*psychology ; Humans ; *Muscle, Skeletal ; }, abstract = {BACKGROUND: The article titled ‘Muscle dysmorphia: Could it be classified as an addiction to body image?’ used Griffiths (2005) addiction components model as the framework in which to define muscle dysmorphia (MD) as an addiction. The authors (Foster, Shorter & Griffiths, 2014) proposed that MD could be re-classified as an addiction to body image.

METHOD AND AIM: In response to the original article, the author of this commentary reflected on the ‘Addiction to body image’ model and the components of addiction as described in the context of MD. This invited commentary aimed to provide opposing viewpoints in order to give a balanced overview on the topic.

RESULTS: It appears as if the components of addictions can be used as a framework in which to define MD. However, systematic empirical evidence had not been provided for the withdrawal symptoms associated with this behavioral addiction. An opposing viewpoint is provided in response to Foster et al.’s (2014) statement that MD is different from other body dysmorphic disorders in regards to cognitive dysfunction, and therefore cannot be explained in the same way.

CONCLUSIONS: Based on the little systematic empirical evidence to date, it may be a bit premature to re-classify MD as an addiction to body image.}, } @article {pmid25570430, year = {2014}, author = {Honda, S and Kohama, T and Tanaka, T and Yoshida, H}, title = {Quantitative assessments of arousal by analyzing microsaccade rates and pupil fluctuations prior to slow eye movements.}, journal = {Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference}, volume = {2014}, number = {}, pages = {2229-2232}, doi = {10.1109/EMBC.2014.6944062}, pmid = {25570430}, issn = {2694-0604}, mesh = {Adult ; Arousal ; Electrooculography/methods ; Humans ; Male ; Pupil/physiology ; *Saccades ; Young Adult ; }, abstract = {It is well known that a decline of arousal level causes of poor performance of movements or judgments. Our previous study indicates that microsaccade (MS) rates and pupil fluctuations change before slow eye movements (SEMs) (Honda et al. 2013). However, SEM detection of this study was obscure and insufficient. In this study, we propose a new SEM detection method and analyze MS rates and pupil fluctuations while subjects maintain their gaze on a target. We modified Shin et al.'s method, which is optimized for EOG (electrooculography) signals, to extract the period of sustaining SEMs using a general eye tracker. After SEM detection, we analyzed MS rates and pupil fluctuations prior to the initiation of SEMs. As a result, we were able to detect SEMs more precisely than in our previous study. Moreover, the results of eye movements and pupil fluctuations analyses show that gradual rise of MS rate and longitudinal miosis are observed prior to the initiation of SEMs, which is consistent with our previous study. These findings suggest that monitoring eye movements and pupil fluctuations may evaluate the arousal level more precisely. Further, we found that these tendencies become more significant when they are restricted to the initial SEMs.}, } @article {pmid25559501, year = {2015}, author = {Moholy, M and Prause, N and Proudfit, GH and S Rahman, A and Fong, T}, title = {Sexual desire, not hypersexuality, predicts self-regulation of sexual arousal.}, journal = {Cognition & emotion}, volume = {29}, number = {8}, pages = {1505-1516}, doi = {10.1080/02699931.2014.993595}, pmid = {25559501}, issn = {1464-0600}, mesh = {*Arousal ; Female ; Humans ; *Libido ; Male ; *Self-Control ; *Sexual Behavior ; Young Adult ; }, abstract = {A person's ability to control their own sexual arousal is important both to reduce the risks associated with some sexual behaviours and to respond sexually with intimate partners. A lack of control over sexual urges is a proposed feature of "hypersexual disorder", though some evidence suggests that sexual desire predicts the self-regulation of sexual arousal better than hypersexuality. In the current study, a sample (N = 116) of men and women recruited from community ads viewed a series of 20-second neutral and sexual films. Before each sexual film, participants were instructed to increase their sexual arousal, decrease their sexual arousal or respond as usual. Higher levels of desire for sex with a partner consistently predicted failures to downregulate sexual arousal. Hypersexuality was unrelated. These findings replicate Winters et al.'s study and extend their findings by including upregulation, women, a new measure of hypersexuality and a higher-trial design.}, } @article {pmid27752432, year = {2015}, author = {Campbell, P and Coulson, M and Ruddle, N and Tornier, I and Pilling, E}, title = {Authors' response on Hoppe et al. (2015) "Effects of a neonicotinoid pesticide on honey bee colonies: a response to the field study by Pilling et al. (2013)". Environ Sci Eur (2015) 27-28.}, journal = {Environmental sciences Europe}, volume = {27}, number = {1}, pages = {31}, pmid = {27752432}, issn = {2190-4707}, abstract = {The published Commentary by Hoppe et al. (Environ Sci Eur 27-28, 2015) makes a number of strong criticisms of Pilling et al. (PLoS One 8:e77193, 2013), which this authors' response will show are either wrong, inaccurate or misleading. A selection of these misrepresentations include a claim that technical thiamethoxam was used rather than the commercial product. This is not true. Pilling et al. (PLoS One 8:e77193, 2013) clearly state that formulated commercial products were used which also included fungicides. It is claimed that there was a failure to quantify colony losses in winter. Again this is not true. These data were readily extractable from the original paper. It is claimed that 70 % of the colonies did not survive. For a multiple year study this is very misleading. The annual colony loss rate was 14.8 % for treated colonies and 16 % for control colonies, well within background colony loss rates reported by the EC Epilobee EU monitoring programme. Concerns are also raised regarding the PLOS One reviewing process. The reality is that Pilling et al. (PLoS One 8:e77193, 2013) was extensively reviewed by five referees during the original review process, followed by a second post-publication editorial review. These inaccurate and misleading statements are then used to infer that the data, methodology and conclusions of low risk to honeybees from Pilling et al. (PLoS One 8:e77193, 2013) are untruthful and misleading. This inference is both absolutely untrue and inappropriate. Pilling et al.'s (PLoS One 8:e77193, 2013) paper is a summary of one the most comprehensive set of field studies ever conducted on honeybees, a fact recognised within both the second review by PLOS One and within the published EFSA Evaluation of Thiamethoxam.}, } @article {pmid27408724, year = {2015}, author = {Seidel, DP and Boyce, MS}, title = {Patch-use dynamics by a large herbivore.}, journal = {Movement ecology}, volume = {3}, number = {}, pages = {7}, pmid = {27408724}, issn = {2051-3933}, abstract = {BACKGROUND: An adaption of the optimal foraging theory suggests that herbivores deplete, depart, and finally return to foraging patches leaving time for regrowth [van Moorter et al., Oikos 118:641-652, 2009]. Inter-patch movement and memory of patches then produce a periodic pattern of use that may define the bounds of a home range. The objective of this work was to evaluate the underlying movements within home ranges of elk (Cervus elaphus) according to the predictions of this theory. Using a spatial temporal permutation scan statistic to identify foraging patches from GPS relocations of cow elk, we evaluated return patterns to foraging patches during the 2012 growing season. Subsequently, we used negative binomial regression to assess environmental characteristics that affect the frequency of returns, and thereby characterize the most successful patches.

RESULTS: We found that elk return to known patches regularly over a season, on average after 15.4 (±5.4 SD) days. Patches in less-rugged terrain, farther from roads and with high productivity were returned to most often when controlling for the time each patch was known to each elk.

CONCLUSIONS: Instead of diffusion processes often used to describe animal movement, our research demonstrates that elk make directed return movements to valuable foraging sites and, as support for Van Moorter et al.'s [Oikos 118:641-652, 2009] model, we submit that these movements could be an integral part of home-range development in wild ungulates.}, } @article {pmid25551356, year = {2015}, author = {Fox, L and Serre, ML and Lippmann, SJ and Rodríguez, DA and Bangdiwala, SI and Gutiérrez, MI and Escobar, G and Villaveces, A}, title = {Spatiotemporal approaches to analyzing pedestrian fatalities: the case of Cali, Colombia.}, journal = {Traffic injury prevention}, volume = {16}, number = {6}, pages = {571-577}, doi = {10.1080/15389588.2014.976336}, pmid = {25551356}, issn = {1538-957X}, mesh = {Accidents, Traffic/*mortality ; Bayes Theorem ; Cities ; Colombia/epidemiology ; Humans ; Public Health ; Spatio-Temporal Analysis ; Walking/*injuries ; }, abstract = {OBJECTIVE: Injuries among pedestrians are a major public health concern in Colombian cities such as Cali. This is one of the first studies in Latin America to apply Bayesian maximum entropy (BME) methods to visualize and produce fine-scale, highly accurate estimates of citywide pedestrian fatalities. The purpose of this study is to determine the BME method that best estimates pedestrian mortality rates and reduces statistical noise. We further utilized BME methods to identify and differentiate spatial patterns and persistent versus transient pedestrian mortality hotspots.

METHODS: In this multiyear study, geocoded pedestrian mortality data from the Cali Injury Surveillance System (2008 to 2010) and census data were utilized to accurately visualize and estimate pedestrian fatalities. We investigated the effects of temporal and spatial scales, addressing issues arising from the rarity of pedestrian fatality events using 3 BME methods (simple kriging, Poisson kriging, and uniform model Bayesian maximum entropy). To reduce statistical noise while retaining a fine spatial and temporal scale, data were aggregated over 9-month incidence periods and censal sectors. Based on a cross-validation of BME methods, Poisson kriging was selected as the best BME method. Finally, the spatiotemporal and urban built environment characteristics of Cali pedestrian mortality hotspots were linked to intervention measures provided in Mead et al.'s (2014) pedestrian mortality review.

RESULTS: The BME space-time analysis in Cali resulted in maps displaying hotspots of high pedestrian fatalities extending over small areas with radii of 0.25 to 1.1 km and temporal durations of 1 month to 3 years. Mapping the spatiotemporal distribution of pedestrian mortality rates identified high-priority areas for prevention strategies. The BME results allow us to identify possible intervention strategies according to the persistence and built environment of the hotspot; for example, through enforcement or long-term environmental modifications.

CONCLUSIONS: BME methods provide useful information on the time and place of injuries and can inform policy strategies by isolating priority areas for interventions, contributing to intervention evaluation, and helping to generate hypotheses and identify the preventative strategies that may be suitable to those areas (e.g., street-level methods: pedestrian crossings, enforcement interventions; or citywide approaches: limiting vehicle speeds). This specific information is highly relevant for public health interventions because it provides the ability to target precise locations.}, } @article {pmid25540840, year = {2015}, author = {Lunkenheimer, K and Prescher, D and Hirte, R and Geggel, K}, title = {Adsorption properties of surface chemically pure sodium perfluoro-n-alkanoates at the air/water interface: counterion effects within homologous series of 1:1 ionic surfactants.}, journal = {Langmuir : the ACS journal of surfaces and colloids}, volume = {31}, number = {3}, pages = {970-981}, doi = {10.1021/la503450k}, pmid = {25540840}, issn = {1520-5827}, abstract = {The unusual behavior of saturation adsorption calculated from experimental equilibrium surface tension (σ(e)) versus logarithm of concentration (c) isotherms within the homologous series of aqueous sodium perfluoro-n-alkanoate solutions represents a particular problem in the adsorption of homologous ionic 1:1 amphiphiles at fluid interfaces. Special precautions were taken to guarantee surface-chemical purity for all solutions, avoiding falsifying effects by surface-active trace impurities. Surprisingly, all homologues' adsorption isotherms reveal ideal surface behavior. The minimal surface area demand per molecule adsorbed for shorter-chain homologues slightly decreases with increasing chain lengths but then goes up steeply after having passed a minimum. A similar feature has been observed with the chemically quite different homologous series of the hydrocarbon surfactants of sodium-n-alkylsulfates. Comparing the corresponding 3D saturation concentrations in the boundary layer and in the bulk, it becomes evident that at high bulk concentrations when boundary layer and bulk concentrations are of the same order of magnitude the adsorption behavior may be treated as that of a pseudononionic surfactant. However, under conditions of the homologues' strongest surface activity, adsorption seems to become increasingly governed by electrostatic repulsion, resulting in increasingly greater cross-sectional areas. Deviation from pseudononionic behavior sets in when the Debye length becomes distinctly greater than the adsorbent's diameter at saturation. Formerly available theories on ionic amphiphiles' adsorption deal either with electrical conditions of surfactant ions and counterions in the adsorption boundary layer or alternatively with pseudononionic behavior neglecting the former theories completely. Warszynski et al.'s novel theoretical model of the "surface quasi-two-dimensional electrolyte" seems to be capable of describing the adsorption of ionic amphiphiles at fluid interfaces in general. We conclude that the conditions of the two alternative approaches may be met within homologous series of ionic amphiphiles as limiting cases only.}, } @article {pmid25538668, year = {2014}, author = {Fox, KC and Thompson, E and Andrews-Hanna, JR and Christoff, K}, title = {Is thinking really aversive? A commentary on Wilson et al.'s "Just think: the challenges of the disengaged mind".}, journal = {Frontiers in psychology}, volume = {5}, number = {}, pages = {1427}, pmid = {25538668}, issn = {1664-1078}, } @article {pmid25536634, year = {2014}, author = {Liu, Q and Li, A and Sun, S and Luo, R and Chen, F}, title = {Reply to Dr. Moschouris et al.'s comment.}, journal = {Journal of B.U.ON. : official journal of the Balkan Union of Oncology}, volume = {19}, number = {4}, pages = {1132}, pmid = {25536634}, issn = {1107-0625}, } @article {pmid25536633, year = {2014}, author = {Moschouris, H and Papadatou, A and Malagari, K}, title = {Comment on Liu et al.'s article: "The true role of mRECIST guideline: does it really estimate viable tumor or merely improve accuracy in hepatocellular carcinoma response evaluation?".}, journal = {Journal of B.U.ON. : official journal of the Balkan Union of Oncology}, volume = {19}, number = {4}, pages = {1131-1132}, pmid = {25536633}, issn = {2241-6293}, mesh = {Carcinoma, Hepatocellular/*therapy ; *Chemoembolization, Therapeutic ; Female ; Humans ; Liver Neoplasms/*therapy ; Male ; }, } @article {pmid25532118, year = {2014}, author = {Zill, JM and Christalle, E and Müller, E and Härter, M and Dirmaier, J and Scholl, I}, title = {Measurement of physician-patient communication--a systematic review.}, journal = {PloS one}, volume = {9}, number = {12}, pages = {e112637}, pmid = {25532118}, issn = {1932-6203}, mesh = {*Communication ; Humans ; *Physician-Patient Relations ; Psychometrics/*methods ; }, abstract = {BACKGROUND: Effective communication with health care providers has been found as relevant for physical and psychological health outcomes as well as the patients' adherence. However, the validity of the findings depends on the quality of the applied measures. This study aimed to provide an overview of measures of physician-patient communication and to evaluate the methodological quality of psychometric studies and the quality of psychometric properties of the identified measures.

METHODS: A systematic review was performed to identify psychometrically tested instruments which measure physician-patient communication. The search strategy included three databases (EMBASE, PsycINFO, PubMed), reference and citation tracking and personal knowledge. Studies that report the psychometric properties of physician-patient communication measures were included. Two independent raters assessed the methodological quality of the selected studies with the COSMIN (COnsensus based Standards for the selection of health status Measurement INtruments) checklist. The quality of psychometric properties was evaluated with the quality criteria of Terwee and colleagues.

RESULTS: Data of 25 studies on 20 measures of physician-patient communication were extracted, mainly from primary care samples in Europe and the USA. Included studies reported a median of 3 out of the nine COSMIN criteria. Scores for internal consistency and content validity were mainly fair or poor. Reliability and structural validity were rated mainly of fair quality. Hypothesis testing scored mostly poor. The quality of psychometric properties of measures evaluated with Terwee et al.'s criteria was rated mainly intermediate or positive.

DISCUSSION: This systematic review identified a number of measures of physician-patient communication. However, further psychometric evaluation of the measures is strongly recommended. The application of quality criteria like the COSMIN checklist could improve the methodological quality of psychometric property studies as well as the comparability of the studies' results.}, } @article {pmid25530319, year = {2015}, author = {Coquart, JB and Mercier, D and Tabben, M and Bosquet, L}, title = {Influence of sex and specialty on the prediction of middle-distance running performances using the Mercier et al.'s nomogram.}, journal = {Journal of sports sciences}, volume = {33}, number = {11}, pages = {1124-1131}, doi = {10.1080/02640414.2014.986499}, pmid = {25530319}, issn = {1466-447X}, mesh = {Adult ; Athletic Performance/*physiology ; Female ; Humans ; Male ; Middle Aged ; Multivariate Analysis ; *Nomograms ; Physical Education and Training ; Running/*physiology ; Sex Factors ; Track and Field/*physiology ; Young Adult ; }, abstract = {The aim was to test the influence of sex and specialty (3000, 5000 and 10000 m) on the validity of middle-distance running performance predictions obtained from the Mercier et al.'s nomogram. Consequently, we examined all official French track running rankings for the 3000-, 5000- and 10000-m events (men and women) from 2006 to 2012. A scoring table was used to determine the runners' specialties. Only runners who performed in the three distance events within the same year were included (75 women and 400 men). The Mercier et al.'s nomogram was used to predict one running performance from the other two. The results showed no significant difference between actual and predicted running performances (P = 0.77). Female runners had significantly lower performances than male runners (P < 0.001). Specialty did not influence performances (P = 0.11). Very high correlations were found between actual and predicted performances (0.91 < r < 0.99), with the exception of women (r = 0.85) in 5000 m. Moreover, low limits of agreement were obtained for male and female runners, whatever the specialty. These results support the validity of the nomogram to predict running performance in the 3000-, 5000- and 10000-m events for male and female runners, whatever the specialty. The predicted running performances may be used in training programmes (e.g., to prescribe tempo runs) and competitions (e.g., to establish split times).}, } @article {pmid25525968, year = {2015}, author = {Li, B and Li, J and Roesky, HW and Zhu, H}, title = {Synthesis and characterization of coinage metal aluminum sulfur species.}, journal = {Journal of the American Chemical Society}, volume = {137}, number = {1}, pages = {162-164}, doi = {10.1021/ja511722a}, pmid = {25525968}, issn = {1520-5126}, abstract = {The synthesis of heterobimetallic cluster with the Al-S-M (M = Cu and Ag) structural unit has been realized for the first time by the reaction of aluminum-dithiol LAl(SH)2 (L = HC[C(Me)N(Ar)]2, Ar = 2,6-iPr2C6H3) with (MesCu)4 and (MesAg)4 (Mes = 2,4,6-Me3C6H2), respectively. The isolated clusters exhibit core structures of Al2Cu4S4 and Al4Ag8S8, respectively. During the formation of the [LAl(SAg)2]4, a side product of LAlS6 is formed. However, the reaction of LAl(SH)2 with excess of sulfur and (MesAg)4 resulted in the formation of LAlS4 as the only product soluble in organic solvents. Both of them represent rare examples of aluminum polysulfides. All compounds were characterized by spectroscopic methods and single crystal X-ray diffraction studies.}, } @article {pmid25524443, year = {2014}, author = {Wan, X and Wang, W and Liu, J and Tong, T}, title = {Estimating the sample mean and standard deviation from the sample size, median, range and/or interquartile range.}, journal = {BMC medical research methodology}, volume = {14}, number = {}, pages = {135}, pmid = {25524443}, issn = {1471-2288}, mesh = {*Algorithms ; Biomedical Research/*statistics & numerical data ; *Computer Simulation ; Humans ; Meta-Analysis as Topic ; Reproducibility of Results ; Review Literature as Topic ; Sample Size ; Statistics as Topic/*methods ; }, abstract = {BACKGROUND: In systematic reviews and meta-analysis, researchers often pool the results of the sample mean and standard deviation from a set of similar clinical trials. A number of the trials, however, reported the study using the median, the minimum and maximum values, and/or the first and third quartiles. Hence, in order to combine results, one may have to estimate the sample mean and standard deviation for such trials.

METHODS: In this paper, we propose to improve the existing literature in several directions. First, we show that the sample standard deviation estimation in Hozo et al.'s method (BMC Med Res Methodol 5:13, 2005) has some serious limitations and is always less satisfactory in practice. Inspired by this, we propose a new estimation method by incorporating the sample size. Second, we systematically study the sample mean and standard deviation estimation problem under several other interesting settings where the interquartile range is also available for the trials.

RESULTS: We demonstrate the performance of the proposed methods through simulation studies for the three frequently encountered scenarios, respectively. For the first two scenarios, our method greatly improves existing methods and provides a nearly unbiased estimate of the true sample standard deviation for normal data and a slightly biased estimate for skewed data. For the third scenario, our method still performs very well for both normal data and skewed data. Furthermore, we compare the estimators of the sample mean and standard deviation under all three scenarios and present some suggestions on which scenario is preferred in real-world applications.

CONCLUSIONS: In this paper, we discuss different approximation methods in the estimation of the sample mean and standard deviation and propose some new estimation methods to improve the existing literature. We conclude our work with a summary table (an Excel spread sheet including all formulas) that serves as a comprehensive guidance for performing meta-analysis in different situations.}, } @article {pmid25519409, year = {2014}, author = {Hossain, A and Beyene, J}, title = {Analysis of baseline, average, and longitudinally measured blood pressure data using linear mixed models.}, journal = {BMC proceedings}, volume = {8}, number = {Suppl 1 Genetic Analysis Workshop 18Vanessa Olmo}, pages = {S80}, pmid = {25519409}, issn = {1753-6561}, support = {R01 GM031575/GM/NIGMS NIH HHS/United States ; }, abstract = {This article compares baseline, average, and longitudinal data analysis methods for identifying genetic variants in genome-wide association study using the Genetic Analysis Workshop 18 data. We apply methods that include (a) linear mixed models with baseline measures, (b) random intercept linear mixed models with mean measures outcome, and (c) random intercept linear mixed models with longitudinal measurements. In the linear mixed models, covariates are included as fixed effects, whereas relatedness among individuals is incorporated as the variance-covariance structure of the random effect for the individuals. The overall strategy of applying linear mixed models decorrelate the data is based on Aulchenko et al.'s GRAMMAR. By analyzing systolic and diastolic blood pressure, which are used separately as outcomes, we compare the 3 methods in identifying a known genetic variant that is associated with blood pressure from chromosome 3 and simulated phenotype data. We also analyze the real phenotype data to illustrate the methods. We conclude that the linear mixed model with longitudinal measurements of diastolic blood pressure is the most accurate at identifying the known single-nucleotide polymorphism among the methods, but linear mixed models with baseline measures perform best with systolic blood pressure as the outcome.}, } @article {pmid25514960, year = {2014}, author = {Ravignani, A and Martins, M and Fitch, WT}, title = {Vocal learning, prosody, and basal ganglia: don't underestimate their complexity.}, journal = {The Behavioral and brain sciences}, volume = {37}, number = {6}, pages = {570-1; discussion 577-604}, doi = {10.1017/S0140525X13004184}, pmid = {25514960}, issn = {1469-1825}, mesh = {*Animal Communication ; Animals ; *Biological Evolution ; *Communication ; Humans ; Primates/*physiology ; Speech/*physiology ; }, abstract = {Ackermann et al.'s arguments in the target article need sharpening and rethinking at both mechanistic and evolutionary levels. First, the authors' evolutionary arguments are inconsistent with recent evidence concerning nonhuman animal rhythmic abilities. Second, prosodic intonation conveys much more complex linguistic information than mere emotional expression. Finally, human adults' basal ganglia have a considerably wider role in speech modulation than Ackermann et al. surmise.}, } @article {pmid25514958, year = {2014}, author = {Petkov, CI and Jarvis, ED}, title = {The basal ganglia within a cognitive system in birds and mammals.}, journal = {The Behavioral and brain sciences}, volume = {37}, number = {6}, pages = {568-9; discussion 577-604}, pmid = {25514958}, issn = {1469-1825}, support = {102961/WT_/Wellcome Trust/United Kingdom ; 102961/Z/13/Z/WT_/Wellcome Trust/United Kingdom ; NC/K000608/1/NC3RS_/National Centre for the Replacement, Refinement and Reduction of Animals in Research/United Kingdom ; }, mesh = {*Animal Communication ; Animals ; *Biological Evolution ; *Communication ; Humans ; Primates/*physiology ; Speech/*physiology ; }, abstract = {The primate basal ganglia are fundamental to Ackermann et al.'s proposal. However, primates and rodents are models for human cognitive functions involving basal ganglia circuits, and links between striatal function and vocal communication come from songbirds. We suggest that the proposal is better integrated in cognitive and/or motor theories on spoken language origins and with more analogous nonhuman animal models.}, } @article {pmid25514947, year = {2014}, author = {Honing, H and Merchant, H}, title = {Differences in auditory timing between human and nonhuman primates.}, journal = {The Behavioral and brain sciences}, volume = {37}, number = {6}, pages = {557-8; discussion 577-604}, doi = {10.1017/S0140525X13004056}, pmid = {25514947}, issn = {1469-1825}, mesh = {*Animal Communication ; Animals ; *Biological Evolution ; *Communication ; Humans ; Primates/*physiology ; Speech/*physiology ; }, abstract = {The gradual audiomotor evolution hypothesis is proposed as an alternative interpretation to the auditory timing mechanisms discussed in Ackermann et al.'s article. This hypothesis accommodates the fact that the performance of nonhuman primates is comparable to humans in single-interval tasks (such as interval reproduction, categorization, and interception), but shows differences in multiple-interval tasks (such as entrainment, synchronization, and continuation).}, } @article {pmid25514946, year = {2014}, author = {Hasson, U and Llano, DA and Miceli, G and Dick, AS}, title = {Does it talk the talk? On the role of basal ganglia in emotive speech processing.}, journal = {The Behavioral and brain sciences}, volume = {37}, number = {6}, pages = {556-7; discussion 577-604}, doi = {10.1017/S0140525X13004044}, pmid = {25514946}, issn = {1469-1825}, support = {R03 DC012125/DC/NIDCD NIH HHS/United States ; }, mesh = {*Animal Communication ; Animals ; *Biological Evolution ; *Communication ; Humans ; Primates/*physiology ; Speech/*physiology ; }, abstract = {Ackermann et al.'s phylogenetic account of speech argues that the basal ganglia imbue speech with emotive content. However, a body of work on auditory/emotive processing is inconsistent with attributing this function exclusively to these structures. The account further overlooks the possibility that the emotion-integration function may be at least in part mediated by the cortico-ponto-cerebellar system.}, } @article {pmid25514945, year = {2014}, author = {Hanakawa, T and Hosoda, C}, title = {Functions of the cortico-basal ganglia circuits for spoken language may extend beyond emotional-affective modulation in adults.}, journal = {The Behavioral and brain sciences}, volume = {37}, number = {6}, pages = {555-6; discussion 577-604}, doi = {10.1017/S0140525X13004032}, pmid = {25514945}, issn = {1469-1825}, mesh = {*Animal Communication ; Animals ; *Biological Evolution ; *Communication ; Humans ; Primates/*physiology ; Speech/*physiology ; }, abstract = {We support Ackermann et al.'s proposal that the cortico-basal ganglia circuits may play essential roles in the evolution of spoken language. Here we discuss further evidence indicating that the cortico-basal ganglia circuits may contribute to various aspects of spoken language including planning, learning, and controlling of speech in adulthood.}, } @article {pmid25501749, year = {2016}, author = {Phan, HP}, title = {Interrelations that foster learning: An investigation of two correlational studies.}, journal = {International journal of psychology : Journal international de psychologie}, volume = {51}, number = {3}, pages = {185-195}, doi = {10.1002/ijop.12127}, pmid = {25501749}, issn = {1464-066X}, mesh = {Achievement ; Adolescent ; Attention ; Female ; Humans ; *Learning ; Longitudinal Studies ; Male ; *Motivation ; Personality Inventory ; Resilience, Psychological ; *Self Efficacy ; Students/*psychology ; }, abstract = {The theoretical tenets of academic engagement, as outlined by Schaufeli and colleagues, have received limited attention. There is credence to indicate that Schaufeli et al.'s conceptualization has educational implications. Extending this avenue of inquiry, we report two longitudinal studies that explore the motivation-related attributes of engagement within the framework of self-efficacy. A number of research questions were developed for examination-for example, does enactive learning experience influence academic achievement, via students' engrossment (i.e. absorption) of a subject matter? Does students' sense of resilience and persistence (i.e. vigor) heighten their self-efficacy beliefs for academic learning? For the two studies (Study 1: 311 Year 11 students; Study 2: 249 Year 12 students), utilizing different cohorts, we measured these constructs at multiple time points. Existing Likert-scale inventories were administered repeatedly, and data collected were analysed using causal modeling procedures. MPlus 7.2 yielded a number of key findings-for example: (a) the positive impact of Time 1 enactive learning experience on Time 2 absorption and vigor, (b) the positive impact of Time absorption on Time 3 self-efficacy, (c) the positive impact of Time 2 absorption on Time 4 achievement and (d) the positive impact of Time 1 self-efficacy on Time 2 absorption and vigor.}, } @article {pmid25498804, year = {2015}, author = {Ji, K and Finkelhor, D}, title = {A meta-analysis of child physical abuse prevalence in China.}, journal = {Child abuse & neglect}, volume = {43}, number = {}, pages = {61-72}, doi = {10.1016/j.chiabu.2014.11.011}, pmid = {25498804}, issn = {1873-7757}, mesh = {Age Factors ; Asia/epidemiology ; Child ; Child Abuse/*statistics & numerical data ; China/epidemiology ; Female ; Humans ; Male ; Physical Abuse/*statistics & numerical data ; Prevalence ; Residence Characteristics ; Risk Factors ; }, abstract = {This study estimated the prevalence of child physical abuse in China, compared Chinese prevalence with international and Asian estimates, and ascertained whether some differences in sample characteristics and methodological factors (e.g., time prevalence, definitional or regional difference) help explain variations in Chinese rates. Based on a meta-analysis of 47 studies found in English- and Chinese-language peer-reviewed journals that involved general populations of students or residents reporting child physical abuse prior to age 18, the life time prevalence of any child physical abuse in China was estimated at 36.6% (95% CI: 30.4-42.7), which was significantly higher than either the international or the Asian estimate in Stoltenborgh et al.'s (2013) study. Chinese prevalence was estimated at 43.1% (95% CI: 36.6-52.5) for minor physical abuse, 26.6% (95% CI: 21.4-31.8) for severe physical abuse, and 7.8% (95% CI: 5.0-10.5) for very severe physical abuse. Subgroup analysis found a significant difference between lifetime and 12-month or less prevalence only for minor physical abuse. The prevalence of any and minor child physical abuse in mainland China was significantly higher than that in non-mainland China. The mainland and non-mainland difference was significant even controlling for definitional and methodological factors as well as sample characteristics. The findings suggested the need to develop educational programs to promote non-violent parenting particularly in mainland China.}, } @article {pmid25486891, year = {2015}, author = {Mishra, D}, title = {On the security flaws in ID-based password authentication schemes for telecare medical information systems.}, journal = {Journal of medical systems}, volume = {39}, number = {1}, pages = {154}, pmid = {25486891}, issn = {1573-689X}, mesh = {Algorithms ; Computer Security/*instrumentation ; Confidentiality ; *Health Information Exchange ; Humans ; Radio Frequency Identification Device/*methods ; Telemedicine/*instrumentation ; }, abstract = {Telecare medical information systems (TMIS) enable healthcare delivery services. However, access of these services via public channel raises security and privacy issues. In recent years, several smart card based authentication schemes have been introduced to ensure secure and authorized communication between remote entities over the public channel for the (TMIS). We analyze the security of some of the recently proposed authentication schemes of Lin, Xie et al., Cao and Zhai, and Wu and Xu's for TMIS. Unfortunately, we identify that these schemes failed to satisfy desirable security attributes. In this article we briefly discuss four dynamic ID-based authentication schemes and demonstrate their failure to satisfy desirable security attributes. The study is aimed to demonstrate how inefficient password change phase can lead to denial of server scenario for an authorized user, and how an inefficient login phase causes the communication and computational overhead and decrease the performance of the system. Moreover, we show the vulnerability of Cao and Zhai's scheme to known session specific temporary information attack, vulnerability of Wu and Xu's scheme to off-line password guessing attack, and vulnerability of Xie et al.'s scheme to untraceable on-line password guessing attack.}, } @article {pmid25483506, year = {2014}, author = {Zimet, GD}, title = {Health care professionals and adolescent vaccination. A call for intervention research.}, journal = {Human vaccines & immunotherapeutics}, volume = {10}, number = {9}, pages = {2629-2630}, pmid = {25483506}, issn = {2164-554X}, mesh = {Diphtheria-Tetanus-acellular Pertussis Vaccines/*administration & dosage ; Female ; Humans ; Male ; Meningococcal Vaccines/*administration & dosage ; Papillomavirus Vaccines/*administration & dosage ; Parents/*psychology ; Patient Acceptance of Health Care/*psychology ; *Physician-Patient Relations ; Vaccination/*statistics & numerical data ; }, abstract = {In their recently published research study, Gargano et al. found that a physician's recommendation and parental health beliefs had significant effects on adolescent vaccination rates and on parental intentions to vaccinate. This research replicates the findings of a number of human papillomavirus (HPV) vaccine-focused research studies, but explores new territory by focusing on all recommended adolescent vaccines: meningococcal-conjugate (MCV4), HPV, influenza, and tetanus, diphtheria, and acellular pertussis (Tdap) vaccines. Although Gargano et al.'s study is relatively small in scale and focuses on only one county in Georgia, their results are consistent with many other research reports, suggesting that their findings are robust and replicable. Most published intervention studies have targeted parents and young adults, with little focus on health care professionals. However, given the centrality of physician recommendation in adolescent vaccination, as shown by Gargano et al., it is clear that the time has come to develop and evaluate interventions that help physicians and other health care professionals to more effectively implement strong and routine recommendations for all adolescent platform vaccines.}, } @article {pmid25483469, year = {2014}, author = {Graitcer, SB and Kim, D and Lindley, M}, title = {Comprehensive efforts to increase healthcare personnel immunization.}, journal = {Human vaccines & immunotherapeutics}, volume = {10}, number = {9}, pages = {2625-2626}, pmid = {25483469}, issn = {2164-554X}, mesh = {*Attitude of Health Personnel ; Cross Infection/*prevention & control ; Female ; *Health Personnel ; Humans ; Male ; Occupational Diseases/*prevention & control ; Vaccination/*statistics & numerical data ; Virus Diseases/*prevention & control ; Whooping Cough/*prevention & control ; }, abstract = {Vaccination of healthcare personnel (HCP) is an important component of worker and patient safety, yet vaccination rates are lagging. The findings from Taddei et al.'s study of healthcare personnel immunization attitudes and practices in Florence, Italy provides further data of the importance of routine assessment of and recommendations for vaccines for HCP in order to improve coverage.}, } @article {pmid25482222, year = {2015}, author = {Langer, MS and Siciliano, RA}, title = {Are blur and disparity complementary cues to depth?.}, journal = {Vision research}, volume = {107}, number = {}, pages = {15-21}, doi = {10.1016/j.visres.2014.10.036}, pmid = {25482222}, issn = {1878-5646}, mesh = {Adult ; Cues ; Depth Perception/*physiology ; Female ; Fixation, Ocular/*physiology ; Humans ; Male ; Photic Stimulation/methods ; Vision Disparity/*physiology ; Vision, Binocular/*physiology ; }, abstract = {The image blur and binocular disparity of a 3D scene point both increase with distance in depth away from fixation. Perceived depth from disparity has been studied extensively and is known to be most precise near fixation. Perceived depth from blur is much less well understood. A recent experiment (Held, R. T, Cooper, E. A., & Banks, M. S. (2012). Current Biology, 22, 426-431) which used a volumetric stereo display found evidence that blur and disparity are complementary cues to depth, namely the disparity cue dominates over the blur cue near the fixation depth and blur dominates over disparity at depths that are far from fixation. Here we present a similar experiment but which used a traditional 3D display so that blur was produced by image processing rather than by the subjects' optics. Contrary to Held et al., we found that subjects did not rely more on blur to discriminate depth at distances far from fixation, even though a sufficient level of blur was available to do so. The discrepancy between the findings of the two studies can be explained in at least two ways. First, Held et al.'s subjects received trial-to-trial feedback in a training phase and may have learned how to perform the task using blur discrimination. Second, Held et al.'s volumetric stereo display may have provided other optical cues that indicated that the blur was real rather than rendered. The latter possibility would have significant implications about how depth is perceived from blur under different viewing conditions.}, } @article {pmid25478143, year = {2014}, author = {MacColl, AD and Aucott, B}, title = {Inappropriate analysis does not reveal the ecological causes of evolution of stickleback armour: a critique of Spence et al. 2013.}, journal = {Ecology and evolution}, volume = {4}, number = {18}, pages = {3509-3513}, pmid = {25478143}, issn = {2045-7758}, abstract = {In a recent paper in this journal, Spence et al. (2013) sought to identify the ecological causes of morphological evolution in three-spined sticklebacks Gasterosteus aculeatus, by examining phenotypic and environmental variation between populations on the island of North Uist, Scotland. However, by using simple qualitative assessments of phenotype and inappropriate measures of environmental variation, Spence et al. have come to a conclusion that is diametrically opposite to that which we have arrived at in studying the same populations. Our criticisms of their paper are threefold: (1) using a binomial qualitative measure of the variation in stickleback armour ("low" versus "minimal" (i.e., "normal" low-plated freshwater sticklebacks versus spineless and/or plateless fish)) does not represent the full range of phenotypes that can be described by quantitative measures of the individual elements of armour. (2) Their use of unspecified test kits, with a probable accuracy of 4 ppm, may not be accurate in the range of water chemistry on North Uist (1 to 30 ppm calcium). (3) Their qualitative assessment of the abundance of brown trout Salmo trutta as the major predator of sticklebacks does not accurately describe the variation in brown trout abundance that is revealed by catch-per-unit-effort statistics. Repeating Spence et al.'s analysis using our own measurements, we find, in direct contradiction to them, that variation in stickleback bony armour is strongly correlated with variation in trout abundance, and unrelated to variation in the concentration of calcium in the lochs in which they live. Field studies in ecology and evolution seldom address the same question in the same system at the same time, and it is salutary that in this rare instance two such studies arrived at diametrically opposite answers.}, } @article {pmid25465312, year = {2015}, author = {Crow, TJ}, title = {Is transition to schizophrenia predicted by anomalous lateralization? Commentary on Cooper et al.'s meta-analysis, 2014.}, journal = {Psychiatry research}, volume = {231}, number = {1}, pages = {92-93}, doi = {10.1016/j.pscychresns.2014.10.024}, pmid = {25465312}, issn = {1872-7123}, mesh = {Brain/*pathology ; Female ; Humans ; Magnetic Resonance Imaging/*methods ; Male ; Multimodal Imaging/*methods ; Psychotic Disorders/*pathology ; }, } @article {pmid25453605, year = {2014}, author = {Blath, J and Kadow, S and Ortgiese, M}, title = {The largest strongly connected component in the cyclical pedigree model of Wakeley et al.}, journal = {Theoretical population biology}, volume = {98}, number = {}, pages = {28-37}, doi = {10.1016/j.tpb.2014.10.001}, pmid = {25453605}, issn = {1096-0325}, mesh = {Algorithms ; Computer Simulation ; Genetics, Population/*methods ; Humans ; *Models, Genetic ; Models, Theoretical ; *Pedigree ; Poisson Distribution ; Population Density ; Probability ; }, abstract = {We establish a link between Wakeley et al.'s (2012) cyclical pedigree model from population genetics and a randomized directed configuration model (DCM) considered by Cooper and Frieze (2004). We then exploit this link in combination with asymptotic results for the in-degree distribution of the corresponding DCM to compute the asymptotic size of the largest strongly connected component S(N) (where N is the population size) of the DCM resp. the pedigree. The size of the giant component can be characterized explicitly (amounting to approximately 80% of the total populations size) and thus contributes to a reduced 'pedigree effective population size'. In addition, the second largest strongly connected component is only of size O(logN). Moreover, we describe the size and structure of the 'domain of attraction' of S(N). In particular, we show that with high probability for any individual the shortest ancestral line reaches S(N) after O(loglogN) generations, while almost all other ancestral lines take at most O(logN) generations.}, } @article {pmid25443102, year = {2014}, author = {Goodman, B}, title = {The debate on climate change and health in the context of ecological public health: a necessary corrective to Costello et al.'s 'biggest global health threat', or co-opted apologists for the neoliberal hegemony?.}, journal = {Public health}, volume = {128}, number = {12}, pages = {1059-1065}, doi = {10.1016/j.puhe.2014.08.017}, pmid = {25443102}, issn = {1476-5616}, mesh = {*Climate Change ; *Dissent and Disputes ; *Ecological and Environmental Phenomena ; Global Health ; Humans ; Politics ; *Public Health ; }, abstract = {The threat posed to global health by climate change has been widely discussed internationally. The United Kingdom public health community seem to have accepted this as fact and have called for urgent action on climate change, often through state interventionist mitigation strategies and the adoption of a risk discourse. Putting aside the climate change deniers' arguments, there are critics of this position who seem to accept climate change as a fact but argue that the market and/or economic development should address the issue. Their view is that carbon reduction (mitigation) is a distraction, may be costly and is ineffective. They argue that what is required is more economic development and progress even if that means a warmer world. Both positions however accept the fact of growth based capitalism and thus fail to critique neoliberal market driven capitalism or posit an alternative political economy that eschews growth. Ecological public health, however, appears to be a way forward in addressing not only social determinants of health but also the political and ecological determinants. This might allow us to consider not just public health but also planetary health and health threats that arise from growth based capitalism.}, } @article {pmid25440212, year = {2014}, author = {Natale, G and Condino, S and Soldani, P and Fornai, F and Mattioli Belmonte, M and Gesi, M}, title = {Natale et. al.'s response to Stecco's fascial nomenclature editorial.}, journal = {Journal of bodywork and movement therapies}, volume = {18}, number = {4}, pages = {588-590}, doi = {10.1016/j.jbmt.2014.06.006}, pmid = {25440212}, issn = {1532-9283}, mesh = {Fascia/*anatomy & histology ; Female ; Humans ; *Leg ; Male ; }, abstract = {Despite their importance in anatomy, physiology, pathology and surgery, the fasciae and the fascial spaces have been poorly described in classic textbooks. This little attention depends on the fact that these fasciae vary in thickness and composition, especially at the cervical level. Indeed, in the main literature they have been described in different forms. Furthermore, the definition itself of the fascia is not consistent in a variety of authors. As a consequence, different criteria have been used to define and classify the fascial systems. In this paper, a brief terminological history and the most common nomenclatures and classifications of the fascia have been summarized.}, } @article {pmid25435589, year = {2014}, author = {Sideridis, G and Simos, P and Papanicolaou, A and Fletcher, J}, title = {Using Structural Equation Modeling to Assess Functional Connectivity in the Brain: Power and Sample Size Considerations.}, journal = {Educational and psychological measurement}, volume = {74}, number = {5}, pages = {733-758}, pmid = {25435589}, issn = {0013-1644}, support = {P50 HD052117/HD/NICHD NIH HHS/United States ; }, abstract = {The present study assessed the impact of sample size on the power and fit of structural equation modeling applied to functional brain connectivity hypotheses. The data consisted of time-constrained minimum norm estimates of regional brain activity during performance of a reading task obtained with magnetoencephalography. Power analysis was first conducted for an autoregressive model with 5 latent variables (brain regions), each defined by 3 indicators (successive activity time bins). A series of simulations were then run by generating data from an existing pool of 51 typical readers (aged 7.5-12.5 years). Sample sizes ranged between 20 and 1,000 participants and for each sample size 1,000 replications were run. Results were evaluated using chi-square Type I errors, model convergence, mean RMSEA (root mean square error of approximation) values, confidence intervals of the RMSEA, structural path stability, and D-Fit index values. Results suggested that 70 to 80 participants were adequate to model relationships reflecting close to not so close fit as per MacCallum et al.'s recommendations. Sample sizes of 50 participants were associated with satisfactory fit. It is concluded that structural equation modeling is a viable methodology to model complex regional interdependencies in brain activation in pediatric populations.}, } @article {pmid25422987, year = {2015}, author = {Alpert, EH and Wenig, BM and Dewey, EH and Su, HK and Dos Reis, L and Urken, ML}, title = {Size distribution of metastatic lymph nodes with extranodal extension in patients with papillary thyroid cancer: a pilot study.}, journal = {Thyroid : official journal of the American Thyroid Association}, volume = {25}, number = {2}, pages = {238-241}, doi = {10.1089/thy.2014.0392}, pmid = {25422987}, issn = {1557-9077}, mesh = {Carcinoma, Papillary/*pathology ; Humans ; Lymph Nodes/*pathology ; Lymphatic Metastasis/*pathology ; Pilot Projects ; Prognosis ; Retrospective Studies ; Thyroid Neoplasms/*pathology ; Tumor Burden ; }, abstract = {BACKGROUND: Extranodal extension (ENE) is a documented negative prognostic factor in patients with papillary thyroid cancer (PTC). ENE is presumed to manifest in larger lymph nodes. Yet, to date, no study has proven this. This is a pilot study that specifically examines the size distribution of positive lymph nodes manifesting ENE in patients with PTC.

METHODS: An Institutional Review Board approved review examined the size of all lymph nodes demonstrating ENE in postoperative PTC patients that underwent surgery for PTC under the care of a single surgeon between 2004 and 2014. All patients in the study had regional metastatic lymph nodes with ENE. Analysis of the size distribution for all lymph nodes with ENE was performed.

RESULTS: A total of 47% of lymph nodes with ENE were ≤10 mm.

CONCLUSIONS: RESULTS indicate that clinically nonevident, small lymph nodes are at risk of harboring aggressive disease biology reflected in ENE. A total of 47% of all nodes fell within Randolph et al.'s classification of "small" lymph nodes, while 59% of the nodes with ENE were <1.5 cm-the threshold size that was deemed to be prognostically significant by Ito et al. It is apparent that clinically nonevident regional lymph nodes can have adverse histologic features and that the previous presumption that nodes with ENE only appear in clinically evident, macroscopic nodes is flawed.}, } @article {pmid25419730, year = {2014}, author = {Lambert, MJ and Ogles, BM}, title = {Common factors: post hoc explanation or empirically based therapy approach?.}, journal = {Psychotherapy (Chicago, Ill.)}, volume = {51}, number = {4}, pages = {500-504}, doi = {10.1037/a0036580}, pmid = {25419730}, issn = {1939-1536}, mesh = {Evidence-Based Medicine/*methods ; Humans ; Mental Disorders/*therapy ; Psychotherapy/*methods ; }, abstract = {Laska, Gurman, and Wampold (2014, pp. 467-481) seek to expand the lens of evidence-based practice by incorporating the common factors perspective. We comment on Laska et al.'s arguments along with the methods used to reach their conclusions. Although we share their view that the common factors explanation for therapeutic equivalence across various orientations observed in the treatment outcome literature is both parsimonious and supported by the scientific evidence, we take issue with their suggestion that there exists a common factors "approach" to treatment in general or evidence-based practice more specifically. We provide clarification and friendly amendments to their language and perspective on the psychotherapy process and outcome research literature and its application in evidence-based practice.}, } @article {pmid25416581, year = {2015}, author = {Gulewitsch, MD and Rosenkranz, T and Barkmann, C and Schlarb, AA}, title = {Measuring Somatic Complaints in Primary School Children: Validation and Revision of the German Children's Somatization Inventory (CSI) and its Parental Version.}, journal = {Child psychiatry and human development}, volume = {46}, number = {5}, pages = {786-799}, pmid = {25416581}, issn = {1573-3327}, mesh = {Abdominal Pain/*diagnosis/psychology ; Child ; Factor Analysis, Statistical ; Female ; Humans ; Irritable Bowel Syndrome/*diagnosis/psychology ; Male ; *Parents ; Proxy ; Psychometrics ; Reproducibility of Results ; *Self Report ; Somatoform Disorders/*diagnosis/psychology ; }, abstract = {The objective was a psychometric examination of a German translation of the Children's Somatization Inventory (CSI) and its parents' version (P-CSI) and a replication of the item selection process of Walker et al. in J Pediatr Psychol 34:430-440 [5] for their revised version to create shorter German versions. Based on a school sample of 1,539 parents and 731 children, we explored the psychometric properties and dimensionality of the original and a shortened revised version. A clinical sample of 70 parental reports served as an additional sample. Walker et al.'s item selection could be largely replicated. Dimensionality differed between samples and versions (original vs. revised), but original DSM-III symptom clusters could mostly be identified. Symptom intensity was associated with age and mental health. Internal consistency, test-retest- and inter-rater reliability were good. Both German versions, the CSI and the P-CSI can be regarded as a useful screening instrument for somatic complaints in children.}, } @article {pmid25400495, year = {2014}, author = {Patterson Silver Wolf Adelv Unegv Waya, DA and Dulmus, CN and Maguin, E and Fava, N}, title = {Refining the Evidence-Based Practice Attitude Scale: An Alternative Confirmatory Factor Analysis.}, journal = {Social work research}, volume = {38}, number = {1}, pages = {47-58}, pmid = {25400495}, issn = {1070-5309}, support = {K23 AA017684/AA/NIAAA NIH HHS/United States ; }, abstract = {Barriers to adopting evidence-based practices into real-world mental health organizations have received considerable attention and study. One particular attempt is Aarons's Evidence-Based Practice Attitude Scale (EBPAS), which measures a worker's attitudes toward adopting new treatments, interventions, and practices. This study follows Aarons's work by conducting a confirmatory factor analysis of the EBPAS administered in a large child and family human service agency in New York state (N = 1,273). Replicating Aarons et al.'s four-factor model of the EBPAS, the authors found that, within the model, the pattern of factor loadings that was apparent in previous investigations held for their data as well. That is, the factor loadings of items within the Divergence subscale were larger for items 5 and 7 and smaller for items 3 and 6. The authors found that both of their alternative models, one that added a residual covariance to items in the Divergence factor and a five-factor model that divided the Divergence factor into two factors, fit their data better than Aarons et al.'s model. They also investigated measurement and structural invariance for workers in community-based and in residential programs using a multiple group analysis. Measurement invariance was supported but factor means and correlations differed.}, } @article {pmid25382634, year = {2015}, author = {Lerner, MD and Lillard, AS}, title = {From false belief to friendship: commentary on Fink, Begeer, Peterson, Slaughter, and de Rosnay.}, journal = {The British journal of developmental psychology}, volume = {33}, number = {1}, pages = {18-20}, doi = {10.1111/bjdp.12070}, pmid = {25382634}, issn = {2044-835X}, mesh = {Child Development/*physiology ; Female ; Humans ; *Interpersonal Relations ; Male ; Social Isolation/*psychology ; Theory of Mind/*physiology ; }, abstract = {Fink, Begeer, Peterson, Slaughter, and de Rosnay (Brit. J. Dev. Psychol, 2015; 33, 1-17) represent a welcome contribution in providing empirical evidence of the link from false belief understanding at Time 1 to mutual friendship 2 years later, controlling for several other possible contributors. This opens a new and important line of inquiry into the practical significance of a Theory of Mind. As is typical of pioneering research, further study is needed to address some issues; here, we point out some of these issues and then briefly discuss the broader implications of Fink et al.'s findings.}, } @article {pmid25381693, year = {2014}, author = {Calvet, D and Laurent, S and Mas, JL}, title = {Response to Varol et al.'s letter.}, journal = {International journal of stroke : official journal of the International Stroke Society}, volume = {9}, number = {8}, pages = {E44-5}, doi = {10.1111/ijs.12323_2}, pmid = {25381693}, issn = {1747-4949}, mesh = {Coronary Artery Disease/*diagnosis/*etiology ; Female ; Humans ; Ischemic Attack, Transient/*complications ; Male ; Stroke/*complications ; Vascular Stiffness/*physiology ; }, } @article {pmid25368576, year = {2014}, author = {Pidgeon, LM and Morcom, AM}, title = {Age-related increases in false recognition: the role of perceptual and conceptual similarity.}, journal = {Frontiers in aging neuroscience}, volume = {6}, number = {}, pages = {283}, pmid = {25368576}, issn = {1663-4365}, support = {G0700704/MRC_/Medical Research Council/United Kingdom ; MR/K026992/1/MRC_/Medical Research Council/United Kingdom ; }, abstract = {Older adults (OAs) are more likely to falsely recognize novel events than young adults, and recent behavioral and neuroimaging evidence points to a reduced ability to distinguish overlapping information due to decline in hippocampal pattern separation. However, other data suggest a critical role for semantic similarity. Koutstaal et al. [(2003) false recognition of abstract vs. common objects in older and younger adults: testing the semantic categorization account, J. Exp. Psychol. Learn. 29, 499-510] reported that OAs were only vulnerable to false recognition of items with pre-existing semantic representations. We replicated Koutstaal et al.'s (2003) second experiment and examined the influence of independently rated perceptual and conceptual similarity between stimuli and lures. At study, young and OAs judged the pleasantness of pictures of abstract (unfamiliar) and concrete (familiar) items, followed by a surprise recognition test including studied items, similar lures, and novel unrelated items. Experiment 1 used dichotomous "old/new" responses at test, while in Experiment 2 participants were also asked to judge lures as "similar," to increase explicit demands on pattern separation. In both experiments, OAs showed a greater increase in false recognition for concrete than abstract items relative to the young, replicating Koutstaal et al.'s (2003) findings. However, unlike in the earlier study, there was also an age-related increase in false recognition of abstract lures when multiple similar images had been studied. In line with pattern separation accounts of false recognition, OAs were more likely to misclassify concrete lures with high and moderate, but not low degrees of rated similarity to studied items. Results are consistent with the view that OAs are particularly susceptible to semantic interference in recognition memory, and with the possibility that this reflects age-related decline in pattern separation.}, } @article {pmid25365954, year = {2015}, author = {Valenti, R and Salvadori, E and Poggesi, A and Ciolli, L and Pescini, F and Nannucci, S and Inzitari, D and Pantoni, L}, title = {Mild cognitive impairment etiologic subtyping using pragmatic and conventional criteria: preliminary experience in the Florence VAS-COG clinic.}, journal = {Aging clinical and experimental research}, volume = {27}, number = {3}, pages = {345-350}, doi = {10.1007/s40520-014-0284-1}, pmid = {25365954}, issn = {1720-8319}, mesh = {Aged ; Cognitive Dysfunction/classification/*etiology ; Dementia/etiology ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; }, abstract = {BACKGROUND: Mild cognitive impairment (MCI) is an abnormal condition defined by the presence of cognitive decline not severe enough to fit dementia criteria. According to Winblad et al.'s criteria, the clinical distinction of MCI subtypes (amnestic/non-amnestic, single/multiple domain) is based on the cognitive profiling (conventional diagnosis) and infers possible different MCI etiologies. MCI prodromic of vascular dementia (Vasc-MCI) is thought to be characterized by a multiple domain profile. In our outpatient clinic (the "Florence VAS-COG clinic"), the diagnosis of MCI and of its different subtypes (vascular, degenerative, mixed) is based on a comprehensive evaluation of clinical and neuroimaging features (pragmatic diagnosis).

AIMS: To compare the pragmatic and conventional diagnoses in terms of etiologic subtyping of MCI.

METHODS: We retrospectively assessed the agreement between the two diagnoses in 30 MCI patients. Agreement was considered present when degenerative MCI was of the amnestic type (single or multiple domain) and Vasc-MCI was of the multiple domain type (amnestic or non-amnestic MCI).

RESULTS: In 15/30 (50 %) patients, the diagnoses were in disagreement: 5/9 (56 %) patients diagnosed with a degenerative MCI type presented a non-amnestic cognitive profile (4 single domain and 1 multiple domain); 10/21 (48 %) Vasc-MCI were classified as non-amnestic single domain.

CONCLUSIONS: The application of MCI etiologic subtyping using pragmatic or conventional diagnoses leads to different results. In our setting, not all the Vasc-MCI patients have a multiple domain profile. Our preliminary study suggests that the cognitive profile of Vasc-MCI is more heterogeneous than previously suggested.}, } @article {pmid25364870, year = {2015}, author = {Finn, JA and Ben-Porath, YS and Tellegen, A}, title = {Dichotomous versus polytomous response options in psychopathology assessment: method or meaningful variance?.}, journal = {Psychological assessment}, volume = {27}, number = {1}, pages = {184-193}, doi = {10.1037/pas0000044}, pmid = {25364870}, issn = {1939-134X}, mesh = {Adolescent ; Analysis of Variance ; Antisocial Personality Disorder/*diagnosis/*psychology ; Female ; Humans ; MMPI/*statistics & numerical data ; Male ; Personality Assessment/*statistics & numerical data ; Psychometrics/*statistics & numerical data ; Reference Values ; Students/psychology ; Young Adult ; }, abstract = {In previous studies, researchers have examined the optimal number of response options for psychological questionnaires. Several have reported increased scale score reliabilities, but few have documented improved external validities. In the present investigation, we followed-up on Cox (2011) and Cox et al.'s (2012) extensive analyses of a clinical assessment instrument, the Minnesota Multiphasic Personality Inventory-2-Restructured Form (MMPI-2-RF). We compared the dichotomous (true/false) response format of this inventory with a 4-choice format. Our sample consisted of 406 undergraduate students from a large Midwestern university who were largely female (64.3%), predominantly Caucasian (76.4%), and had a mean age of 19.24 years. Internal-structural analyses confirmed that more response options increase reliabilities, but the effects were small. The differences between correlations with external criteria were very rarely statistically significant, and the few that were did not consistently favor either format. We recommend that in future response-format investigations the internal-structural analyses continue to be combined with evaluations of relevant external correlations.}, } @article {pmid25362538, year = {2015}, author = {Holmes, M and Fuller-Tyszkiewicz, M and Skouteris, H and Broadbent, J}, title = {Reply to Dakanalis et al.'s 'efforts to make clearer the relationship between body dissatisfaction and binge eating'.}, journal = {Eating and weight disorders : EWD}, volume = {20}, number = {1}, pages = {147-148}, pmid = {25362538}, issn = {1590-1262}, mesh = {Binge-Eating Disorder/*psychology ; Body Image/*psychology ; Bulimia/*psychology ; *Emotions ; Female ; Humans ; *Models, Psychological ; }, } @article {pmid25359621, year = {2015}, author = {Lajoie, JM and Shusta, EV}, title = {Introducing glycophage arrays: facile production, purification and patterning of glycophages.}, journal = {Biotechnology journal}, volume = {10}, number = {1}, pages = {20-21}, doi = {10.1002/biot.201400591}, pmid = {25359621}, issn = {1860-7314}, support = {T32 GM008349/GM/NIGMS NIH HHS/United States ; T32 HG002760/HG/NHGRI NIH HHS/United States ; R01NS071513/NS/NINDS NIH HHS/United States ; }, mesh = {Glycomics/*methods ; Polysaccharides/*chemistry ; Protein Array Analysis/*methods ; Proteins/*chemistry ; }, abstract = {Glycosylation is a widespread post-translational modification that plays important roles in health and disease. As glycan sequence and structure are not directly coded into the genome, our understanding of glycans and their functions in biological systems is much more primitive than that of DNA and proteins.Recently, printed glycan microarrays (glycoarrays) have emerged as powerful, high-throughput tools for screening glycan-protein interactions[1,2], and have been applied in disease detection [3], drug discovery [4], the study of immunity [5], and host-pathogen interactions [1, 2], among others.Unfortunately, glycoarray applications are currently limited by the expensive and complex methods available to synthesize glycans or alternatively, by the challenges in identifying and tagging glycans from natural sources [6, 7]. In this issue of Biotechnology Journal, Çelik et al. [8] introduce a potentially powerful new method for facile, scalable production, and purification of glycans compatible with microarray patterning. Çelik et al.’s [8] approach is based on innovative deployment of filamentous phage display so that the displayed proteins can be tagged with specific glycans of interest (glycophages) and subsequently patterned in array format.}, } @article {pmid25355470, year = {2014}, author = {Kim, E and Zhang, Z and Wang, Y and Zeng, D}, title = {Power calculation for comparing diagnostic accuracies in a multi-reader, multi-test design.}, journal = {Biometrics}, volume = {70}, number = {4}, pages = {1033-1041}, pmid = {25355470}, issn = {1541-0420}, support = {U01 CA079778/CA/NCI NIH HHS/United States ; U10 CA180794/CA/NCI NIH HHS/United States ; U10 CA180820/CA/NCI NIH HHS/United States ; U01-CA 079778/CA/NCI NIH HHS/United States ; }, mesh = {*Algorithms ; Computer Simulation ; Data Interpretation, Statistical ; Diagnosis, Computer-Assisted/*methods ; *Models, Statistical ; *Observer Variation ; *ROC Curve ; Reproducibility of Results ; *Research Design ; }, abstract = {Receiver operating characteristic (ROC) analysis is widely used to evaluate the performance of diagnostic tests with continuous or ordinal responses. A popular study design for assessing the accuracy of diagnostic tests involves multiple readers interpreting multiple diagnostic test results, called the multi-reader, multi-test design. Although several different approaches to analyzing data from this design exist, few methods have discussed the sample size and power issues. In this article, we develop a power formula to compare the correlated areas under the ROC curves (AUC) in a multi-reader, multi-test design. We present a nonparametric approach to estimate and compare the correlated AUCs by extending DeLong et al.'s (1988, Biometrics 44, 837-845) approach. A power formula is derived based on the asymptotic distribution of the nonparametric AUCs. Simulation studies are conducted to demonstrate the performance of the proposed power formula and an example is provided to illustrate the proposed procedure.}, } @article {pmid25351828, year = {2015}, author = {Obafemi-Ajayi, T and Miles, JH and Takahashi, TN and Qi, W and Aldridge, K and Zhang, M and Xin, SQ and He, Y and Duan, Y}, title = {Facial structure analysis separates autism spectrum disorders into meaningful clinical subgroups.}, journal = {Journal of autism and developmental disorders}, volume = {45}, number = {5}, pages = {1302-1317}, pmid = {25351828}, issn = {1573-3432}, mesh = {Biomarkers ; Child ; Child Development Disorders, Pervasive/*diagnosis ; Cognition Disorders/complications/diagnosis ; Face/*anatomy & histology ; Humans ; Language Disorders/complications/diagnosis ; Male ; Regression, Psychology ; }, abstract = {Varied cluster analysis were applied to facial surface measurements from 62 prepubertal boys with essential autism to determine whether facial morphology constitutes viable biomarker for delineation of discrete Autism Spectrum Disorders (ASD) subgroups. Earlier study indicated utility of facial morphology for autism subgrouping (Aldridge et al. in Mol Autism 2(1):15, 2011). Geodesic distances between standardized facial landmarks were measured from three-dimensional stereo-photogrammetric images. Subjects were evaluated for autism-related symptoms, neurologic, cognitive, familial, and phenotypic variants. The most compact cluster is clinically characterized by severe ASD, significant cognitive impairment and language regression. This verifies utility of facially-based ASD subtypes and validates Aldridge et al.'s severe ASD subgroup, notwithstanding different techniques. It suggests that language regression may define a unique ASD subgroup with potential etiologic differences.}, } @article {pmid25325407, year = {2015}, author = {Sellbom, M and Wygant, DB and Drislane, LE}, title = {Elucidating the Construct Validity of the Psychopathic Personality Inventory Triarchic Scales.}, journal = {Journal of personality assessment}, volume = {97}, number = {4}, pages = {374-381}, doi = {10.1080/00223891.2014.962654}, pmid = {25325407}, issn = {1532-7752}, mesh = {Adolescent ; Adult ; Aged ; Alabama ; Antisocial Personality Disorder/*diagnosis/*psychology ; Community Participation ; *Emotions ; Female ; Humans ; Male ; Middle Aged ; Personality Assessment/*standards ; Personality Inventory ; Prisoners ; Regression Analysis ; Reproducibility of Results ; Young Adult ; }, abstract = {This study sought to replicate and extend Hall and colleagues' (2014) work on developing and validating scales from the Psychopathic Personality Inventory (PPI) to index the triarchic psychopathy constructs of boldness, meanness, and disinhibition. This study also extended Hall et al.'s initial findings by including the PPI Revised (PPI-R). A community sample (n = 240) weighted toward subclinical psychopathy traits and a male prison sample (n = 160) were used for this study. Results indicated that PPI-Boldness, PPI-Meanness, and PPI-Disinhibition converged with other psychopathy, personality, and behavioral criteria in ways conceptually expected from the perspective of the triarchic psychopathy model, including showing very strong convergent and discriminant validity with their Triarchic Psychopathy Measure counterparts. These findings further enhance the utility of the PPI and PPI-R in measuring these constructs.}, } @article {pmid25324790, year = {2014}, author = {Shaffer, F and McCraty, R and Zerr, CL}, title = {A healthy heart is not a metronome: an integrative review of the heart's anatomy and heart rate variability.}, journal = {Frontiers in psychology}, volume = {5}, number = {}, pages = {1040}, pmid = {25324790}, issn = {1664-1078}, abstract = {Heart rate variability (HRV), the change in the time intervals between adjacent heartbeats, is an emergent property of interdependent regulatory systems that operate on different time scales to adapt to challenges and achieve optimal performance. This article briefly reviews neural regulation of the heart, and its basic anatomy, the cardiac cycle, and the sinoatrial and atrioventricular pacemakers. The cardiovascular regulation center in the medulla integrates sensory information and input from higher brain centers, and afferent cardiovascular system inputs to adjust heart rate and blood pressure via sympathetic and parasympathetic efferent pathways. This article reviews sympathetic and parasympathetic influences on the heart, and examines the interpretation of HRV and the association between reduced HRV, risk of disease and mortality, and the loss of regulatory capacity. This article also discusses the intrinsic cardiac nervous system and the heart-brain connection, through which afferent information can influence activity in the subcortical and frontocortical areas, and motor cortex. It also considers new perspectives on the putative underlying physiological mechanisms and properties of the ultra-low-frequency (ULF), very-low-frequency (VLF), low-frequency (LF), and high-frequency (HF) bands. Additionally, it reviews the most common time and frequency domain measurements as well as standardized data collection protocols. In its final section, this article integrates Porges' polyvagal theory, Thayer and colleagues' neurovisceral integration model, Lehrer et al.'s resonance frequency model, and the Institute of HeartMath's coherence model. The authors conclude that a coherent heart is not a metronome because its rhythms are characterized by both complexity and stability over longer time scales. Future research should expand understanding of how the heart and its intrinsic nervous system influence the brain.}, } @article {pmid25309472, year = {2014}, author = {Zanolie, K and Pecher, D}, title = {Number-induced shifts in spatial attention: a replication study.}, journal = {Frontiers in psychology}, volume = {5}, number = {}, pages = {987}, pmid = {25309472}, issn = {1664-1078}, abstract = {In a spatial attention paradigm, Fischer et al. (2003) showed that merely perceiving a number shifted attention according to the magnitude of the number. Low numbers shifted attention to the left and high numbers shifted attention to the right. This suggests that numbers are represented by the mental number line - a spatial image schema that is ordered from left to right with increasing magnitude. In six experiments, we used the spatial attention paradigm of Fischer et al. (2003) to investigate if and when such mental representations are activated. Participants detected visual targets that were preceded by low and high numbers. Between experiments we manipulated how participants processed the number. Participants either merely perceived the number, as in the experiments by Fischer et al. (2003) processed the number's parity, or processed the number's magnitude. Our results provide little support for the idea that numbers shift spatial attention. Only in one of the two experiments in which participants processed number magnitude did participants respond faster to targets in congruent locations (left for low magnitudes and right for high magnitudes) than in incongruent locations. In the other five experiments number magnitude did not affect spatial attention. This shows, in contrast to Fischer et al.'s (2003) results, that the mental number line is not activated automatically but at best only when it is contextually relevant. Furthermore, these results suggest that image schemas in general may be context-dependent rather than fundamental to mental concepts.}, } @article {pmid26815900, year = {2014}, author = {Rao, B and Kamal, T and Vafe, J and Moss, M}, title = {Distal femoral replacement for selective periprosthetic fractures above a total knee arthroplasty.}, journal = {European journal of trauma and emergency surgery : official publication of the European Trauma Society}, volume = {40}, number = {2}, pages = {191-199}, pmid = {26815900}, issn = {1863-9941}, abstract = {BACKGROUND AND AIM: The management of distal femur periprosthetic fractures in the elderly remains a challenge. The aim of this study was to evaluate the results of distal segmental femur replacement as an alternative to fixation in complex distal femoral periprosthetic fractures in elderly patients.

METHODS: Twelve patients were included in this prospective study, with a mean age of 78 years (range 68-90 years); incidentally, all were female. Fractures of the distal femur were classified as per Kim et al.'s classification (Clin Orthop Relat Res 446:167-175, 2006); our series included eight patients with type III and four patients with type II periprosthetic fractures. All 12 patients were treated with segmental distal femur replacement (Zimmer Inc., Warsaw, IN, USA). Nine patients required 90 cm and three patients required 130 cm of distal femur segment with a rotating hinge knee prosthesis.

RESULTS: The mean follow up period was 20 months (range 15-28 months), with no major surgical complications reported. The mean duration of hospital stay following surgery was 12 days (range 7-36 days). All patients were mobilising full weight-bearing by day 3. All patients returned to their prior living arrangements. Ten patients returned to their original domicile, with one patient being discharged to a care home requiring minimal ambulatory assistance. The remaining two patients returned to their care homes.

CONCLUSIONS: WOMAC scores improved from the pre-injury state with a mean of 49.62 to 72.54 post-surgery (p-value of 0.0001). The Knee Society scores, possible only following surgery, had a mean value of 72. The mean VAS pain score was 1.75 (0 = no pain to 10 = worst pain ever felt). The average range of knee flexion was from 4° to 89° (range -5° to 110°). The mean SF-36 physical functioning score was 45.64 [range 40.70-48.90; standard deviation (SD) -2.62] and the mean SF-36 mental functioning score was 52.94 (range 45.8-57.70; SD -3.38).}, } @article {pmid26973926, year = {2014}, author = {Sweet, SN and Fortier, MS and Strachan, SM and Blanchard, CM and Boulay, P}, title = {Testing a Longitudinal Integrated Self-Efficacy and Self-Determination Theory Model for Physical Activity Post-Cardiac Rehabilitation.}, journal = {Health psychology research}, volume = {2}, number = {1}, pages = {1008}, pmid = {26973926}, issn = {2420-8124}, abstract = {Self-determination theory and self-efficacy theory are prominent theories in the physical activity literature, and studies have begun integrating their concepts. Sweet, Fortier, Strachan and Blanchard (2012) have integrated these two theories in a cross-sectional study. Therefore, this study sought to test a longitudinal integrated model to predict physical activity at the end of a 4-month cardiac rehabilitation program based on theory, research and Sweet et al.'s cross-sectional model. Participants from two cardiac rehabilitation programs (N=109) answered validated self-report questionnaires at baseline, two and four months. Data were analyzed using Amos to assess the path analysis and model fit. Prior to integration, perceived competence and self-efficacy were combined, and labeled as confidence. After controlling for 2-month physical activity and cardiac rehabilitation site, no motivational variables significantly predicted residual change in 4-month physical activity. Although confidence at two months did not predict residual change in 4-month physical activity, it had a strong positive relationship with 2-month physical activity (β=0.30, P<0.001). The overall model retained good fit indices. In conclusion, results diverged from theoretical predictions of physical activity, but self-determination and self-efficacy theory were still partially supported. Because the model had good fit, this study demonstrated that theoretical integration is feasible.}, } @article {pmid26229772, year = {2014}, author = {da Rocha, VL and Marques, GL and da Silva, LJ and di Macedo Bernardes, TA and de Moraes, FB}, title = {Clinical and radiographic medium-term evaluation on patients with developmental dysplasia of the hip, who were submitted to open reduction, capsuloplasty and Salter osteotomy.}, journal = {Revista brasileira de ortopedia}, volume = {49}, number = {1}, pages = {51-55}, pmid = {26229772}, issn = {2255-4971}, abstract = {OBJECTIVE: to evaluate the clinical and radiographic medium-term results from surgical treatment of developmental dysplasia through open reduction, Salter et al.'s osteotomy and capsuloplasty.

METHODS: 13 patients were evaluated, 13 hips treated surgically by the proposed technique between 2004 and 2011. A clinical and radiographic evaluation was conducted by Dutoit et al. and Severin et al. criteria, respectively.

RESULTS: the acetabular preoperative index for the 13 surgically treated hips ranged from 27° to 50° (average of 36), and after surgical correction to 18.5° (10-28°), so that the evaluations of preoperative and postoperative acetabular indexes showed up significant statistic reduction (p < 0.05). Regarding the postoperative clinical evaluation, it was found: nine excellent hips (69.2%), three good ones (23.1%), no fair hips (0%) and a poor one (7.7%). In radiographic evaluation, it was found: six excellent hips (46.1%), three good ones (23.1%), no fair hips (0%) and four poor ones (30.8%). Therefore, favorable results were obtained (92.3%), with grouped hips with excellent and good ratings as satisfactory and with fair and bad ratings as unsatisfactory. It is also important to notice that there was no significance among occurrence of complications, the patient's age, the time of surgery and the preoperative acetabular index (p > 0.05). As complications occurred, it was found that three subluxations and a subluxation associated with avascular necrosis of the femoral head.

CONCLUSION: open reduction, Salter et al.'s osteotomy and capsuloplasty are seen to be a viable option for the treatment of developmental dysplasia of the hip, according to clinical and radiological medium-term evaluations.}, } @article {pmid25926861, year = {2014}, author = {Balao, F and García-Castaño, JL}, title = {AFLPsim: an R package to simulate and detect dominant markers under selection in hybridizing populations.}, journal = {Plant methods}, volume = {10}, number = {}, pages = {40}, pmid = {25926861}, issn = {1746-4811}, abstract = {BACKGROUND: In spite of a large diversity of approaches to investigate loci under selection from a population genetic perspective, very few programs have been specifically designed to date to test selection in hybrids using dominant markers. In addition, simulators of dominant markers are very scarce and they do not usually take into account hybridization.

RESULTS: Here, we present a new, multifunctional, R package for dominant genetic markers, AFLPsim. This package can simulate dominant markers in hybridizing populations and implements genome scan methods for detecting outlier dominant loci in hybrids. In addition, it includes tools for further manipulating the results, plotting them and other tasks. We describe and tabulate the major functions implemented in AFLPsim. In addition, we provide some demonstration of its use and we perform a comparative study with other software. Finally, we conclude by briefly describing the input and output formats.

CONCLUSIONS: The R package AFLPsim application provides several useful tools in the context of hybridization studies. It can simulate dominant markers in hybridizing populations and predict their demographic evolution. In addition, we implement a new genome scan method for detecting outlier dominant loci in hybrids, which shows a rather high sensitivity and is very conservative in comparison with Gagnaire et al.'s, Bayescan and introgress. The application is downloadable at http://cran.r-project.org/web/packages/AFLPsim/.}, } @article {pmid28809270, year = {2013}, author = {Yaakob, Z and Bshish, A and Ebshish, A and Tasirin, SM and Alhasan, FH}, title = {Hydrogen Production by Steam Reforming of Ethanol over Nickel Catalysts Supported on Sol Gel Made Alumina: Influence of Calcination Temperature on Supports.}, journal = {Materials (Basel, Switzerland)}, volume = {6}, number = {6}, pages = {2229-2239}, pmid = {28809270}, issn = {1996-1944}, abstract = {Selecting a proper support in the catalyst system plays an important role in hydrogen production via ethanol steam reforming. In this study, sol gel made alumina supports prepared for nickel (Ni) catalysts were calcined at different temperatures. A series of (Ni/AlS.G.) catalysts were synthesized by an impregnation procedure. The influence of varying the calcination temperature of the sol gel made supports on catalyst activity was tested in ethanol reforming reaction. The characteristics of the sol gel alumina supports and Ni catalysts were affected by the calcination temperature of the supports. The structure of the sol gel made alumina supports was transformed in the order of γ → (γ + θ) → θ-alumina as the calcination temperature of the supports increased from 600 °C to 1000 °C. Both hydrogen yield and ethanol conversion presented a volcano-shaped behavior with maximum values of 4.3 mol/mol ethanol fed and 99.5%, respectively. The optimum values were exhibited over Ni/AlS.G800 (Ni catalyst supported on sol gel made alumina calcined at 800 °C). The high performance of the Ni/AlS.G800 catalyst may be attributed to the strong interaction of Ni species and sol gel made alumina which lead to high nickel dispersion and small particle size.}, } @article {pmid27008510, year = {2013}, author = {Druehl, L}, title = {Algal taxonomy forum: Algal Taxonomist, Let Serendipity Reign!.}, journal = {Journal of phycology}, volume = {49}, number = {2}, pages = {226}, doi = {10.1111/jpy.12041}, pmid = {27008510}, issn = {0022-3646}, abstract = {The publication of a mini-review by Olivier De Clerck et al. in this issue of the Journal of Phycology presented an opportunity to open a dialogue on challenges faced by contemporary algal taxonomists. The Editorial Office solicited the following two additional contributions in response to De Clerck et al.'s paper; the responses were edited solely for clarity, space and format.}, } @article {pmid25574069, year = {2013}, author = {Lee, CJ and Kim, D}, title = {A Comparative Analysis of the Validity of US State- and County-Level Social Capital Measures and Their Associations with Population Health.}, journal = {Social indicators research}, volume = {111}, number = {1}, pages = {307-326}, pmid = {25574069}, issn = {0303-8300}, support = {P20 CA095856/CA/NCI NIH HHS/United States ; }, abstract = {The goals of this study were to validate a number of available collective social capital measures at the U.S. state and county levels, and to examine the relative extent to which these social capital measures are associated with population health outcomes. Measures of social capital at the U.S. state level included aggregate indices based on the Annenberg National Health Communication Survey (ANHCS) and the Behavioral Risk Factor Surveillance System (BRFSS), Petris Social Capital Index (PSCI), Putnam's index, and Kim et al.'s scales. County-level measures consisted of Rupasingha et al.'s social capital index (RGFI) and a BRFSS-derived measure. These measures, except for the PSCI, showed evidence of acceptable validity. Moreover, we observed differences across the social capital measures in their associations with population health outcomes. The implications of the findings for future research in this area are discussed.}, } @article {pmid25973181, year = {2013}, author = {Carthy, ER}, title = {Commentary on "estimation of newborn risk for child or adolescent obesity: lessons from longitudinal birth cohorts".}, journal = {Annals of medicine and surgery (2012)}, volume = {2}, number = {1}, pages = {3-4}, pmid = {25973181}, issn = {2049-0801}, abstract = {Childhood obesity is an increasingly prevalent problem, associated with obesity later in life, and a sequalae of health problems such as metabolic syndrome and an increased risk of coronary heart disease. Poor nutrition and a lack of physical activity are said to be causes of obesity development, with genetic factors and heritability also implicated. However, there are established, identifiable risk factors associated with the future development of obesity, both in childhood, and adolescence. These include parental weight before pregnancy, gestational weight gain, pre-pregnancy maternal smoking, as well as numerous socioeconomic factors.(1-4) Studies have also shown that once obese, children can find it very difficult to lose the excess weight,(5) with long-term management methods having shown poor efficacy.(5) Therefore, preventative strategies are becoming a high priority to battle the ever-increasing epidemic of childhood obesity. This study by Morandi et al.(6) is the first longitudinal study to analyse the predictive properties of early life risk factors for obesity, and propose a subsequent predictive algorithm to identify newborns most at risk of becoming obese in childhood and adolescence. Morandi et al.'s study aimed to develop a clinically useful formula, which could be used to identify the risk of future obesity in newborns, thereby enabling more efficient implementation of prevention strategies.(6) The lifetime Northern Finland Birth Cohort 1986 (NFBC 1986) was used to form predictive equations for both childhood and adolescent obesity, based on established risk factors: parental BMI, birth weight, maternal gestational weight gain, and socioeconomic factors. A genetic score was also created based on 39 BMI/obesity-associated polymorphisms. Validation studies were performed on both a retrospective cohort of children from Veneto, Italy, and a prospective cohort of children from Massachusetts, USA.}, } @article {pmid26357170, year = {2012}, author = {Talbot, J and Gerth, J and Hanrahan, P}, title = {An Empirical Model of Slope Ratio Comparisons.}, journal = {IEEE transactions on visualization and computer graphics}, volume = {18}, number = {12}, pages = {2613-2620}, doi = {10.1109/TVCG.2012.196}, pmid = {26357170}, issn = {1941-0506}, abstract = {Comparing slopes is a fundamental graph reading task and the aspect ratio chosen for a plot influences how easy these comparisons are to make. According to Banking to 45°, a classic design guideline first proposed and studied by Cleveland et al., aspect ratios that center slopes around 45° minimize errors in visual judgments of slope ratios. This paper revisits this earlier work. Through exploratory pilot studies that expand Cleveland et al.'s experimental design, we develop an empirical model of slope ratio estimation that fits more extreme slope ratio judgments and two common slope ratio estimation strategies. We then run two experiments to validate our model. In the first, we show that our model fits more generally than the one proposed by Cleveland et al. and we find that, in general, slope ratio errors are not minimized around 45°. In the second experiment, we explore a novel hypothesis raised by our model: that visible baselines can substantially mitigate errors made in slope judgments. We conclude with an application of our model to aspect ratio selection.}, } @article {pmid27857606, year = {2012}, author = {Murakami, Y and Takada, S}, title = {Rigor of cell fate decision by variable p53 pulses and roles of cooperative gene expression by p53.}, journal = {Biophysics (Nagoya-shi, Japan)}, volume = {8}, number = {}, pages = {41-50}, pmid = {27857606}, issn = {1349-2942}, abstract = {Upon DNA damage, the cell fate decision between survival and apoptosis is largely regulated by p53-related networks. Recent experiments found a series of discrete p53 pulses in individual cells, which led to the hypothesis that the cell fate decision upon DNA damage is controlled by counting the number of p53 pulses. Under this hypothesis, Sun et al. (2009) modeled the Bax activation switch in the apoptosis signal transduction pathway that can rigorously "count" the number of uniform p53 pulses. Based on experimental evidence, here we use variable p53 pulses with Sun et al.'s model to investigate how the variability in p53 pulses affects the rigor of the cell fate decision by the pulse number. Our calculations showed that the experimentally anticipated variability in the pulse sizes reduces the rigor of the cell fate decision. In addition, we tested the roles of the cooperativity in PUMA expression by p53, finding that lower cooperativity is plausible for more rigorous cell fate decision. This is because the variability in the p53 pulse height is more amplified in PUMA expressions with more cooperative cases.}, } @article {pmid26504738, year = {2012}, author = {Shalizi, CR}, title = {Comment on "Why and When 'Flawed' Social Network Analyses Still Yield Valid Tests of no Contagion".}, journal = {Statistics, politics, and policy}, volume = {3}, number = {1}, pages = {5}, pmid = {26504738}, issn = {2194-6299}, support = {R01 NS047493/NS/NINDS NIH HHS/United States ; }, abstract = {VanderWeele et al.'s paper is a useful contribution to the on-going scientific conversation about the detection of contagion from purely observational data. It is especially helpful as a corrective to some of the more extreme statements of Lyons (2011). Unfortunately, this paper, too, goes too far in some places, and so needs some correction itself.}, } @article {pmid26598144, year = {2011}, author = {Papajak, E and Zheng, J and Xu, X and Leverentz, HR and Truhlar, DG}, title = {Perspectives on Basis Sets Beautiful: Seasonal Plantings of Diffuse Basis Functions.}, journal = {Journal of chemical theory and computation}, volume = {7}, number = {10}, pages = {3027-3034}, doi = {10.1021/ct200106a}, pmid = {26598144}, issn = {1549-9618}, abstract = {We present a perspective on the use of diffuse basis functions for electronic structure calculations by density functional theory and wave function theory. We especially emphasize minimally augmented basis sets and calendar basis sets. We base our conclusions on our previous experience with commonly computed quantities, such as bond energies, barrier heights, electron affinities, noncovalent (van der Waals and hydrogen bond) interaction energies, and ionization potentials, on Stephens et al.'s results for optical rotation and on our own new calculations (presented here) of polarizabilities and of potential energy curves of van der Waals complexes. We emphasize the benefits of partial augmentation of the higher-zeta basis sets in preference to full augmentation at a lower ζ level. Benefits and limitations of the use of fully, partially, and minimally augmented basis sets are reviewed for different electronic structure methods and molecular properties. We have found that minimal augmentation is almost always enough for density functional theory (DFT) when applied to ionization potentials, electron affinities, atomization energies, barrier heights, and hydrogen-bond energies. For electric dipole polarizabilities, we find that augmentation beyond minimal has an average effect of 8% at the polarized triple-ζ level and 5% at the polarized quadruple-ζ level. The effects are larger for potential energy curves of van der Waals complexes. The effects are also larger for wave function theory (WFT). Even for WFT though, full augmentation is not needed for most purposes, and a level of augmentation between minimal and full is optimal for most problems. The calendar basis sets named after the months provide a convergent sequence of partially augmented basis sets that can be used for such calculations. The jun-cc-pV(T+d)Z basis set is very useful for MP2-F12 calculations of barrier heights and hydrogen bond strengths.}, } @article {pmid29558172, year = {2009}, author = {Ricklefs, RE}, title = {A Brief Response to Brooker et al.'s Comment.}, journal = {The American naturalist}, volume = {174}, number = {6}, pages = {928-931}, doi = {10.1086/648059}, pmid = {29558172}, issn = {1537-5323}, } @article {pmid26161737, year = {2009}, author = {Craig, IW and Haworth, CM and Plomin, R}, title = {Commentary on "A Role for the X Chromosome in Sex Differences in Variability in General Intelligence?" (Johnson et al., 2009).}, journal = {Perspectives on psychological science : a journal of the Association for Psychological Science}, volume = {4}, number = {6}, pages = {615-621}, doi = {10.1111/j.1745-6924.2009.01170.x}, pmid = {26161737}, issn = {1745-6916}, support = {G19/2/MRC_/Medical Research Council/United Kingdom ; }, abstract = {Johnson et al.'s (2009) article highlights the role of X-chromosomal genes in general intelligence and draws attention to their potential role in explaining the observed greater variance for this trait in males and their excess at both extremes of the distribution. We note that this would result from a simple additive effect of X-linked intelligence genes and also discuss the potentially important contribution of recessive deleterious loci. The buffering effect of heterozygosity in females will be partly constrained by the skewing of X-inactivation patterns increasing the variance of females beyond what is expected. Furthermore, escape of some X-linked genes from in-activation may also be relevant to male-female variance comparisons. We also comment on the difficulty of establishing the extent to which the X chromosome is enriched for intelligence genes and point out that their estimates of the proportion of genes influencing general intelligence that might be located on the X chromosome rely on some doubtful premises, especially concerning the likely equivalence of X-linked gene action in males and females. Finally, we discuss the increasingly compelling evidence for the accumulation of genes on the X chromosome that have selective benefit to males, including those implicated infertility and some manifestations of intelligence.}, } @article {pmid26158966, year = {2009}, author = {Yarkoni, T}, title = {Big Correlations in Little Studies: Inflated fMRI Correlations Reflect Low Statistical Power-Commentary on Vul et al. (2009).}, journal = {Perspectives on psychological science : a journal of the Association for Psychological Science}, volume = {4}, number = {3}, pages = {294-298}, doi = {10.1111/j.1745-6924.2009.01127.x}, pmid = {26158966}, issn = {1745-6916}, abstract = {Vul, Harris, Winkielman, and Pashler (2009), (this issue) argue that correlations in many cognitive neuroscience studies are grossly inflated due to a widespread tendency to use nonindependent analyses. In this article, I argue that Vul et al.'s primary conclusion is correct, but for different reasons than they suggest. I demonstrate that the primary cause of grossly inflated correlations in whole-brain fMRI analyses is not nonindependence, but the pernicious combination of small sample sizes and stringent alpha-correction levels. Far from defusing Vul et al.'s conclusions, the simulations presented suggest that the level of inflation may be even worse than Vul et al.'s empirical analysis would suggest.}, } @article {pmid26158965, year = {2009}, author = {Nichols, TE and Poline, JB}, title = {Commentary on Vul et al.'s (2009) "Puzzlingly High Correlations in fMRI Studies of Emotion, Personality, and Social Cognition".}, journal = {Perspectives on psychological science : a journal of the Association for Psychological Science}, volume = {4}, number = {3}, pages = {291-293}, doi = {10.1111/j.1745-6924.2009.01126.x}, pmid = {26158965}, issn = {1745-6916}, abstract = {The article "Puzzlingly High Correlations in fMRI Studies of Emotion, Personality, and Social Cognition" (Vul, Harris, Winkielman, & Pashler, 2009, this issue) makes a broad case that current practice in neuroimaging methodology is deficient. Vul et al. go so far as to demand that authors retract or restate results, which we find wrongly casts suspicion on the confirmatory inference methods that form the foundation of neuroimaging statistics. We contend the authors' argument is overstated and that their work can be distilled down to two points already familiar to the neuroimaging community: that the multiple testing problem must be accounted for, and that reporting of methods and results should be improved. We also illuminate their concerns with standard statistical concepts such as the distinction between estimation and inference and between confirmatory and post hoc inferences, which makes their findings less puzzling.}, } @article {pmid26158975, year = {2008}, author = {Mayer, RE}, title = {Incorporating Individual Differences Into the Science of Learning: Commentary on Sternberg et al. (2008).}, journal = {Perspectives on psychological science : a journal of the Association for Psychological Science}, volume = {3}, number = {6}, pages = {507-508}, doi = {10.1111/j.1745-6924.2008.00093.x}, pmid = {26158975}, issn = {1745-6916}, abstract = {Sternberg, Grigorenko, and Zhang (2008, this issue) make a valiant effort to reinvigorate the somewhat dormant field of cognitive style by showing the implications of cognitive style for instruction and assessment. In support of their call to differentiate instruction for different kinds of learners, they summarize evidence showing that people learn better from a broad instructional method that is sensitive to multiple cognitive styles than they do from a narrow instructional method that is mainly addressed to one cognitive style. In support of their call for using multiple measures of learning potential, they summarize evidence showing that learning outcomes are better predicted by multiple measures of learning potential than by a single measure. In this commentary, I briefly examine Sternberg et al.'s claim that cognitive styles matter for instruction and assessment.}, } @article {pmid27877992, year = {2008}, author = {Vora, AM}, title = {Study of superconducting state parameters of ternary metallic glasses through pseudopotential approach.}, journal = {Science and technology of advanced materials}, volume = {9}, number = {2}, pages = {025017}, pmid = {27877992}, issn = {1468-6996}, abstract = {A theoretical investigation on the screening dependence of the superconducting state parameters (SSPs) viz. the electron-phonon coupling strength λ, the Coulomb pseudopotential μ∗, the transition temperature TC, the isotope effect exponent α and the effective interaction strength N0V of some ternary metallic glasses such as Ti50Be34Zr10, (Mo0.6Ru0.4)78B22, (Mo0.6Ru0.4)80B20, (Mo0.4Ru0.6)80P20, (Mo0.6Ru0.4)70Si30, (Mo0.6Ru0.4)84B16, (Mo0.6Ru0.4)72Si28, (Mo0.6Ru0.4)86B14, (Mo0.6Ru0.4)76Si24, (Mo0.6Ru0.4)78Si22, (Mo0.6Ru0.4)80Si20, (Mo0.6Ru0.4)82Si18 and (Mo0.6Ru0.4)80P20 is reported for the first time using Ashcroft's empty core (EMC) model potential. Five local field correction functions proposed by Hartree (H), Taylor (T), Ichimaru-Utsumi (IU), Farid et al (F) and Sarkar et al (S) are used in the present investigation to study the effect of screening on the aforesaid properties. It is observed that λ and TC are reasonably sensitive to the selection of the local field correction functions, whereas μ∗, α and N0V show weak dependences on the local field correction functions. The transition temperature TC obtained from the H-local field correction function is found to be in excellent agreement with available experimental data. Also, the present results are found to be in qualitative agreement with other earlier reported data, which confirms the existence of the superconducting phase in the above ternary metallic glasses.}, } @article {pmid28903278, year = {2007}, author = {Liu, Y and Yamaguchi, Y and Ke, C}, title = {Reducing the Discrepancy Between ASTER and MODIS Land Surface Temperature Products.}, journal = {Sensors (Basel, Switzerland)}, volume = {7}, number = {12}, pages = {3043-3057}, doi = {10.3390/s7123043}, pmid = {28903278}, issn = {1424-8220}, abstract = {Human-induced global warming has significantly increased the importance ofsatellite monitoring of land surface temperature (LST) on a global scale. The MODerate-resolution Imaging Spectroradiometer (MODIS) provides a 1-km resolution LST productwith almost daily coverage of the Earth, invaluable to both local and global change studies.The Advanced Spaceborne Thermal Emission Reflection Radiometer (ASTER) provides aLST product with a high spatial resolution of 90-m and a 16-day recurrent cycle,simultaneously acquired at the same height and nadir view as MODIS. ASTER andMODIS are complementary in resolution, offering a unique opportunity for scale-relatedstudies. ASTER and MODIS LST have been widely used but the errors in LST were mostlydisregarded. Correction of ASTER-to-MODIS LST discrepancies is essential for studiesreliant upon the joint use of these sensors. In this study, we compared three correctionapproaches: the Wan et al.'s approach, the refined Wan et al.'s approach, and thegeneralized split window (GSW) algorithm based approach. The Wan et al.'s approachcorrects the MODIS 1-km LST using MODIS 5-km LST. The refined approach modifiesthe Wan et al.'s approach through incorporating ASTER emissivity and MODIS 5-km data.The GSW algorithm approach does not use MODIS 5-km but only ASTER emissivity data. We examined the case over a semi-arid terrain area for the part of the Loess Plateau of China. All the approaches reduced the ASTER-to-MODIS LST discrepancy effectively. With terrain correction, the original ASTER-to-MODIS LST difference reduced from 2.7±1.28 K to -0.1±1.87 K for the Wan et al.'s approach, 0.2±1.57 K for the refined approach, and 0.1±1.33 K for the GSW algorithm based approach. Among all the approaches, the GSW algorithm based approach performed best in terms of mean, standard deviation, root mean square root, and correlation coefficient.}, } @article {pmid28197959, year = {2006}, author = {Choulakian, V}, title = {Taxicab Correspondence Analysis.}, journal = {Psychometrika}, volume = {71}, number = {2}, pages = {333-345}, pmid = {28197959}, issn = {1860-0980}, abstract = {Taxicab correspondence analysis is based on the taxicab singular value decomposition of a contingency table, and it shares some similar properties with correspondence analysis. It is more robust than the ordinary correspondence analysis, because it gives uniform weights to all the points. The visual map constructed by taxicab correspondence analysis has a larger sweep and clearer perspective than the map obtained by correspondence analysis. Two examples are provided.}, } @article {pmid28682198, year = {2001}, author = {Treasure, DC and Duda, JL and Hall, HK and Roberts, GC and Ames, C and Maehr, ML}, title = {Clarifying Misconceptions and Misrepresentations in Achievement Goal Research in Sport: A Response to Harwood, Hardy, and Swain.}, journal = {Journal of sport & exercise psychology}, volume = {23}, number = {4}, pages = {317-329}, doi = {10.1123/jsep.23.4.317}, pmid = {28682198}, issn = {1543-2904}, abstract = {In a recent article, Harwood, Hardy, and Swain (2000) presented what they termed a critical analysis of the conceptualization and measurement of achievement goals in sport. The purpose of the present article is to challenge their interpretation of achievement goal theory and to question many of their subsequent recommendations. Specifically, the present response will focus on Harwood et al.'s (a) interpretation of Nicholls' personal theories of achievement; (b) their contention that task involvement cannot exist in competitive sport; (c) the proposed tripartite conceptualization of goal involvement states; (d) their understanding of the relationship between the way an individual conceptualizes ability and the foundation of dispositional goal orientations; and (e) their criticisms of the way dispositional goal orientations have been measured in sport. Theoretical frameworks are always a work in progress. To this end, we concur with the spirit of Harwood et al.'s article which implies that our conceptual models should be continuously questioned, tested, and extended. However, we believe their interpretation and recommendations do little to enhance our conceptual understanding of achievement goal theory in sport.}, } @article {pmid28547607, year = {2001}, author = {Gotelli, NJ and Entsminger, GL}, title = {Swap and fill algorithms in null model analysis: rethinking the knight's tour.}, journal = {Oecologia}, volume = {129}, number = {2}, pages = {281-291}, doi = {10.1007/s004420100717}, pmid = {28547607}, issn = {1432-1939}, abstract = {Community assembly rules are often inferred from patterns in presence-absence matrices. A challenging problem in the analysis of presence-absence matrices has been to devise a null model algorithm to produce random matrices with fixed row and column sums. Previous studies by Roberts and Stone [(1990) Oecologia 83:560-567] and Manly [(1995) Ecology 76:1109-1115] used a "Sequential Swap" algorithm in which submatrices are repeatedly swapped to produce null matrices. Sanderson et al. [(1998) Oecologia 116:275-283] introduced a "Knight's Tour" algorithm that fills an empty matrix one cell at a time. In an analysis of the presence-absence matrix for birds of the Vanuatu islands, Sanderson et al. obtained different results from Roberts and Stone and concluded that "results from previous studies are generally flawed". However, Sanderson et al. did not investigate the statistical properties of their algorithm. Using simple probability calculations, we demonstrate that their Knight's Tour is biased and does not sample all unique matrices with equal frequency. The bias in the Knight's Tour arises because the algorithm samples exhaustively at each step before retreating in sequence. We introduce an unbiased Random Knight's Tour that tests only a small number of cells and retreats by removing a filled cell from anywhere in the matrix. This algorithm appears to sample unique matrices with equal frequency. The Random Knight's Tour and Sequential Swap algorithms generate very similar results for the large Vanuatu matrix, and for other presence-absence matrices we tested. As a further test of the Sequential Swap, we constructed a set of 100 random matrices derived from the Vanuatu matrix, analyzed them with the Sequential Swap, and found no evidence that the algorithm is prone to Type I errors (rejecting the null hypothesis too frequently). These results support the original conclusions of Roberts and Stone and are consistent with Gotelli's [(2000) Ecology 81:2606-2621] Type I and Type II error tests for the Sequential Swap. In summary, Sanderson et al.'s Knight's Tourgenerates large variances and does not sample matrices equiprobably. In contrast, the Sequential Swap generates results that are very similar to those of an unbiased Random Knight's Tour, and is not overly prone to Type I or Type II errors. We suggest that the statistical properties of proposed null model algorithms be examined carefully, and that their performance judged by comparisons with artificial data sets of known structure. In this way, Type I and Type II error frequencies can be quantified, and different algorithms and indices can be compared meaningfully.}, } @article {pmid29313990, year = {2000}, author = {Bjørnstad, ON}, title = {Cycles and synchrony: two historical 'experiments' and one experience.}, journal = {The Journal of animal ecology}, volume = {69}, number = {5}, pages = {869-873}, doi = {10.1046/j.1365-2656.2000.00444.x}, pmid = {29313990}, issn = {1365-2656}, abstract = {1. Theoretical models predict that spatial synchrony should be enhanced in cyclic populations due to nonlinear phase-locking. 2. This is supported by Rohani et al.'s (1999) comparison of spatial synchrony of epidemics in two childhood diseases prior to and during the vaccination era. Measles is both more synchronous and more cyclic before vaccination. Whooping cough, in contrast, is more synchronous during the vaccination era, during which multiannual fluctuations are also more conspicuous. 3. Steen et al. (1990) analysed historic records of cyclic rodents, to show that cyclicity was lost during the early part of the 20th century. I reanalyse the data, and find that the loss of cyclicity is associated with loss of regional synchrony. 4. I use a coupled map lattice model to show that imperfect phase-locking provides an alternative explanation for regionwide synchrony of cyclic populations.}, } @article {pmid28085651, year = {1999}, author = {Perry, KD}, title = {Effects of Outdoor Pyrotechnic Displays on the Regional Air Quality of Western Washington State.}, journal = {Journal of the Air & Waste Management Association (1995)}, volume = {49}, number = {2}, pages = {146-155}, doi = {10.1080/10473289.1999.10463791}, pmid = {28085651}, issn = {2162-2906}, abstract = {Data from a PM25 (i.e., Dp < 2.5 mm) particulate matter monitoring network was used to quantify the effects of outdoor pyrotechnic displays on the regional air quality of western Washington State. Linear regression and principal component analysis demonstrated that the fine par-ticulate matter generated by these displays was primarily composed of Sr, K, V, Ti, Ba, Cu, Pb, Mg, Al, S, Mn, Zn,and soot. The maximum 24-hour averaged PM2.5 mass concentration apportioned to the pyrotechnic displays by absolute principal component scores regression analysis was 18.5 mg/m[3]. The majority of this mass (54%) was composed of K and S, which originated from the combustion of black powder. The distribution of smoke emissions from the displays closely resembled the population distribution of western Washington. The PM2.5 aerosol monitoring network tracked the pyrotechnic smoke plume for a period of two days as it was advected by low-level winds. The geometric mass mean diameter of the K particles was ~0.7 mm after transport of ~100 km. In the absence of rain, which is the primary sink for particles of this size, the particulate matter generated by the pyrotechnic displays could have an atmospheric residence time of more than one week.}, } @article {pmid27699380, year = {1999}, author = {Moehr, JR}, title = {Evaluation of a Field Test of Computers for the Doctor's Office. (Reflections on P.L. Reichertz et al.'s paper: Evaluation of a Field Test of Computers for the Doctor's Office).}, journal = {Yearbook of medical informatics}, volume = {}, number = {1}, pages = {257-261}, pmid = {27699380}, issn = {2364-0502}, } @article {pmid27699375, year = {1999}, author = {Rautaharju, PM}, title = {The Birth of Automatic ECG Screening by Digital Electronic Computer. (Reflections on H.V. Pipberger et al.'s paper: Automatic Screening of Normal and Abnormal Electrocardiograms by Means of a Digital Electronic Computer).}, journal = {Yearbook of medical informatics}, volume = {}, number = {1}, pages = {183-185}, pmid = {27699375}, issn = {2364-0502}, } @article {pmid27699374, year = {1999}, author = {van Ginneken, AM}, title = {Diagnostic Support: Towards the Intelligent Integrated Reference Source. (Reflections on R.A. Miller et al.'s paper: INTERNIST-1: An experimental computer-based diagnostic consultant for general internal medicine).}, journal = {Yearbook of medical informatics}, volume = {}, number = {1}, pages = {175-179}, pmid = {27699374}, issn = {2364-0502}, } @article {pmid27699371, year = {1999}, author = {Hasman, A}, title = {Computer-Aided Diagnosis of Abdominal Pain. (Reflections on F.T. De Dombal et al.'s paper: Computer-Aided Diagnosis of Acute Abdominal Pain).}, journal = {Yearbook of medical informatics}, volume = {}, number = {1}, pages = {122-124}, pmid = {27699371}, issn = {2364-0502}, } @article {pmid27699369, year = {1999}, author = {Kalsson, D and Åhlfeltd, H}, title = {A Comment on the Help-System: A Program for Medical Decision Making from Early 1970s. (Reflections on H. Warner et al.'s paper: HELP - A Program for Medical Decision-Making).}, journal = {Yearbook of medical informatics}, volume = {}, number = {1}, pages = {103-106}, pmid = {27699369}, issn = {2364-0502}, } @article {pmid28565212, year = {1998}, author = {Niewiarowski, PH and Dunham, AE}, title = {EFFECTS OF MORTALITY RISK AND GROWTH ON A MODEL OF REPRODUCTIVE EFFORT: WHY THE SHINE AND SCHWARZKOPF MODEL IS NOT GENERAL.}, journal = {Evolution; international journal of organic evolution}, volume = {52}, number = {4}, pages = {1236-1241}, doi = {10.1111/j.1558-5646.1998.tb01852.x}, pmid = {28565212}, issn = {1558-5646}, abstract = {Using data and reanalysis of a model published by Shine and Schwarzkopf (1992) we reject the two unsubstantiated assertions made by Shine et al. (1996) about modeling the evolution of reproductive effort in squamate reptiles: (1) mortality schedules do not affect predictions of the Shine and Schwarzkopf (1992) model; and (2) growth rates that would affect the predictions of the original model are biologically unreasonable. On the basis of these two points alone, we strongly reject Shine et al.'s (1996) claim that a critique by Niewiarowski and Dunham (1994) actually reinforces the original conclusions of Shine and Schwarzkopf (1992). Furthermore, results and data presented here are strong enough to severely circumscribe the generality of the Shine and Schwarzkopf (1992) model. Though we do not provide data or new analyses of the potential effects of offspring size variation, we reaffirm the position of Niewiarowski and Dunham (1994) that the sensitivity of the Shine and Schwarzkopf (1992) model to such effects should be explored before using it as a basis for structuring future research on the evolution of reproductive effort in squamate reptiles.}, } @article {pmid28657465, year = {1998}, author = {Laws, KR}, title = {WHY LEOPARDS NEVER CHANGE THEIR SPOTS: A REPLY TO MOSS, TYLER, AND JENNINGS.}, journal = {Cognitive neuropsychology}, volume = {15}, number = {5}, pages = {467-479}, doi = {10.1080/026432998381113}, pmid = {28657465}, issn = {1464-0627}, abstract = {Laws, Evans, Hodges, and McCarthy (1995) documented a selective impairment for associative knowledge about living things in the post-encephalitic patient SE. By contrast, Moss, Tyler, and Jennings (1997) recently described a selective loss of visual knowledge for living things in the same patient. The apparent contradiction in these papers highlights novel and critical methodological issues in the study of category-specific disorders. A main contention of this paper is that Moss et al.'s data do not meet sufficient conditions for demonstrating a category-specific naming deficit for living things. One implication of this is that their experiments may suffer from a confounding variable that encourages an underestimation of SE's visual knowledge. Finally, it is argued that Moss et al.'s theoretical interpretation of SE's deficit receives no empirical support.}, } @article {pmid28568350, year = {1998}, author = {Janz, N and Nylin, S}, title = {BUTTERFLIES AND PLANTS: A PHYLOGENETIC STUDY.}, journal = {Evolution; international journal of organic evolution}, volume = {52}, number = {2}, pages = {486-502}, doi = {10.1111/j.1558-5646.1998.tb01648.x}, pmid = {28568350}, issn = {1558-5646}, abstract = {A database on host plant records from 437 ingroup taxa has been used to test a number of hypotheses on the interaction between butterflies and their host plants using phylogenetic methods (simple character optimization, concentrated changes test, and independent contrasts test). The butterfly phylogeny was assembled from various sources and host plant clades were identified according to Chase et al.'s rbcL-based phylogeny. The ancestral host plant appears to be associated within a highly derived rosid clade, including the family Fabaceae. As fossil data suggest that this clade is older than the butterflies, they must have colonized already diversified plants. Previous studies also suggest that the patterns of association in most insect-plant interactions are more shaped by host shifts, through colonization and specialization, than by cospeciation. Consequently, we have focused explicitly on the mechanisms behind host shifts. Our results confirm, in the light of new phylogenetic evidence, the pattern reported by Ehrlich and Raven that related butterflies feed on related plants. We show that host shifts have generally been more common between closely related plants than between more distantly related plants. This finding, together with the possibility of a higher tendency of recolonizing ancestral hosts, helps to explain the apparent large-scale conservation in the patterns of association between insects and their host plants, patterns which at the same time are more flexible on a more detailed level. Plant growth form was an even more conservative aspect of the interaction between butterflies and their host plants than plant phylogeny. However, this is largely explained by a higher probability of colonizations and host shifts while feeding on trees than on other growth forms.}, } @article {pmid28313318, year = {1993}, author = {Holyoak, M and Crowley, PH}, title = {Avoiding erroneously high levels of detection in combinations of semi-independent tests : An application to testing for density dependence.}, journal = {Oecologia}, volume = {95}, number = {1}, pages = {103-114}, pmid = {28313318}, issn = {1432-1939}, abstract = {A randomization procedure is proposed which allows statistical tests to be combined into a single test to maintain specified and acceptable levels of false detection. This method was applied to the problem of detecting density dependence in 135 unpublished time-series (of ≥10 generations) from insect populations, and to simulated density-dependent and density-independent data, so that the correctness of observed levels of detection from the published data could be verified. To allow the application of the randomization procedure to Bulmer's (1975) tests and Varley and Gradwell's (1960) test, these were recast as randomization tests. The randomization procedure was tested with 39 combinations of tests for density dependence (and limitation/attraction); it generally producedcombined tests with levels of detection that were intermediate between detection levels of the constituent tests (and hence was limite by these). The specified rate of false detection (5%) was never exceeded (by more than 1%) when combined tests were applied to time-series from a random-walk model. Two different combinations of tests produced levels of detection from the published time-series which were slightly greater than their constituent tests when they were combined into single tests. These were the randomized form of Bulmer's (1975) first test with the tests of Pollard et al. (1987) and Reddingius and den Boer (1989) with the randomized form of Bulmer's second test. The combination of Bulmer's first and Pollard et al.'s test produced a greater level of detection (21.5%) than any other single test or combination of tests. These results were confirmed by the analysis of modelled density dependent data. Although the increase in power of combinations of tests over single tests is small with the data we used, the combined tests (listed above) had rates of detection that were less influenced by the form of data (of two forms of density-dependent data) than were their constituent tests. Hence, it appears that the combined tests are of greater generality than single test statistics. The method presented here for combining several statistical tests into a single randomization test is applicable in many other areas of ecology where we wish to apply several tests and take the most probable result of these; and if the tests being conducted are, or can be expressed as, randomization tests.}, } @article {pmid29865588, year = {1992}, author = {Ishay, JS and Ganor, E}, title = {External micromorphology of the frons plate and its adjacent areas in workers of the oriental hornet.}, journal = {Journal of morphology}, volume = {213}, number = {1}, pages = {1-13}, doi = {10.1002/jmor.1052130102}, pmid = {29865588}, issn = {1097-4687}, abstract = {The micromorphology of the frons and the adjacent regions in young workers (1-24 hr of age) of the Oriental hornet Vespa orientalis and some adult worker hornets is described. The young workers still lack globular secretions at the bases of the setae. Such secretions do occur at the bases of the setae in the adult workers and are composed mainly of the elements Si, Al, S, Mg, Ca, Cl, and Fe. Contiguous with each of the ocelli is a gland that also secretes minerals. Young workers usually have a relatively large concentration of Ca in the glands behind the paired ocelli. The gland associated with the median anterior ocellus opens by an elongated sutura coronalis in the frons and contains various elements, predominantly Si, but also Ca. The setae (hairs) on the frons are arranged in concentric circles around each of the ocelli; they are long in the upper part of the frons but shorten gradually toward the tip of the frons. The tip lacks hair, but the cuticle bears elevated scales that project as cuticular protuberences. It appears that the ocelli and their associated glands, and the entire frons plate with its hairs and glands at the bases of the hairs in this region, comprise an equilibrium "organ" that senses changes in gravity. © 1992 Wiley-Liss, Inc.}, } @article {pmid28313111, year = {1989}, author = {Cameron, GN and Spencer, SR}, title = {Rapid leaf decay and nutrient release in a chinese tallow forest.}, journal = {Oecologia}, volume = {80}, number = {2}, pages = {222-228}, pmid = {28313111}, issn = {1432-1939}, abstract = {The Chinese tallow tree, Sapium sebiferum, was introduced to the Texas Gulf Coast in the early 1900's and has spread into coastal prairie habitats. Since coastal prairie contains few deciduous trees, we studied leaf fall dynamics, rate of decomposition, and the quantity and rate of nutrient input from decomposing tallow leaves. Among-year leaf fall averaged 382.6 g·m[-2]·yr[-1], similar to other south temperat deciduous forests and about as predicted by Meentemeyer et al.'s (1982) AE-lignin model. Decay of tallow leaves (k=-4.33) was much more rapid than native black willow (k=-0.35) and than other temperate deciduous trees (k=-0.77). The ratio of lignin to initial nitrogen concentration, highly correlated with rate of decomposition for hardwood trees, was low for Chinese tallow and may contribute to rapid leaf decay. Taking AE and lignin content into account, Meentemeyer's (1984) model predicted k=-1.39 for Chinese tallow and k=-0.88 for black willow. Decay of tallow was much faster but decay of willow was slower than predicted, suggesting that decay on the coastal prairie may be controlled by factors other than lignin content and climate. N, P, and K characteristically accumulate as leaves decay. However, these elements did not accumulate as tallow leaves decayed, possibly because high densities of Armadillidium vulgare, a detritivore, reduced immobilization of elements by microbes. This would result in increased turnover of these elements. Accumulation of Al, Fe, Zn, and S in decaying tallow litter may be related to flood-drain cycles on coastel prairie clay soils. Ca, N, K, Mg, and S were added to forest soil in greatest amounts from decaying tallow leaves. Concentrations of P, K, NO3-N, Zn, Mn, and Fe were significantly higher and Mg and Na were significantly lower in forest than in prairie soil, raising the possibility that Chinese tallow trees altered the distribution of nutrients in the soil profile. We conclude that the Chinese tallow tree may enhance productivity in ecosystems to which it has been introduced by addition of nutrients from rapid decay of leaves.}, } @article {pmid28581083, year = {1988}, author = {King, BH}, title = {SEX-RATIO MANIPULATION IN RESPONSE TO HOST SIZE BY THE PARASITOID WASP SPALANGIA CAMERONI: A LABORATORY STUDY.}, journal = {Evolution; international journal of organic evolution}, volume = {42}, number = {6}, pages = {1190-1198}, doi = {10.1111/j.1558-5646.1988.tb04179.x}, pmid = {28581083}, issn = {1558-5646}, abstract = {The prediction of Charnov et al.'s (1981) host-size model that there should be a negative relationship between host size and wasp sex ratio (proportion sons) was supported for Spalangia cameroni, a solitary parasitoid wasp. The relationship was shown to be a result of offspring sex manipulation by females in response to host size rather than a result of differential mortality of the sexes. A major assumption of the host-size model is that host size has a greater effect on the ultimate reproductive success of emerging female wasps than of males. This assumption was not supported. Host size had a positive effect on the size of both male and female S. cameroni. However, neither host size nor wasp size affected longevity, production of offspring by females, or ability of males to compete for mates. Host size may differentially affect the reproductive success of female and male wasps through effects on other aspects of reproductive success. Tests of the assumptions of offspring sex-ratio manipulation hypotheses are scarce but critical, not only for parasitoid wasps, but also for other organisms.}, } @article {pmid28564363, year = {1987}, author = {Bush, RM and Smouse, PE and Ledig, FT}, title = {THE FITNESS CONSEQUENCES OF MULTIPLE-LOCUS HETEROZYGOSITY: THE RELATIONSHIP BETWEEN HETEROZYGOSITY AND GROWTH RATE IN PITCH PINE (PINUS RIGIDA MILL.).}, journal = {Evolution; international journal of organic evolution}, volume = {41}, number = {4}, pages = {787-798}, doi = {10.1111/j.1558-5646.1987.tb05853.x}, pmid = {28564363}, issn = {1558-5646}, abstract = {Positive correlations between measures of "fitness" and the number of electrophoretic loci for which an individual is heterozygous have been observed in many species. Two major hypotheses have been proposed to explain this phenomenon: inbreeding depression and overdominance. Until recently, there has been no way to distinguish between these hypotheses. The overdominance model devised by Smouse (1986) is used here in a reanalysis of Ledig et al.'s (1983) study of heterozygosity and growth rate in eight populations of pitch pine and is contrasted with an inbreeding-depression analysis. Ledig et al. (1983) regressed mean growth rate per heterozygosity class on the number of heterozygous loci, a method of analysis which, although it points to general trends in the data, does not differentiate between hypotheses. The correlations they obtained in four populations were significant only because regressing on the means eliminates most of the sum of squares for error and does not weight the unequally sized heterozygosity classes. Reanalysis of Ledig et al.'s data using individuals, not means, showed no significant correlations between heterozygosity and fitness. A major assumption of Smouse's overdominance model is that genetic polymorphism is in part a reflection of selection for heterozygotes at genetic equlibrium. The homozygote for the most frequent allele at a locus should be more fit than a homozygote for a less frequent allele, with the heterozygote superior to both homozygotes. Smouse's model predicts a negative, linear relationship between fitness and "adaptive distance," a variable that for a heterozygote is zero and for homozygotes is equal to the inverse of the frequency of the corresponding allele. The adaptive-distance model accounted for between 15% and 50% of the variation in growth rate within eight P. rigida population samples by accounting for genotypic differences at eight polymorphic loci. This is over twice as much of the variation in growth rate accounted for by Ledig et al.'s (1983) analysis using individuals. Significant correlations were found between adaptive distance and growth rate in four of the eight populations, but in only two of the populations were more of the partial coefficients negative than positive, as would be predicted by the overdominance hypothesis. The remaining two populations in which correlations were significant did not lend themselves to such clear-cut interpretation, as the majority of the partial coefficients were positive. Positive partial coefficients indicate that the growth rate of the heterozygote is inferior to that of at least one of the homozygotes. The adaptive-distance analysis provides evidence that specific genotypes do play a role in determining growth rate in pitch pine. The correlation between growth rate and adaptive distance increased significantly with the age of the population, possibly reflecting competition subsequent to crown closure.}, } @article {pmid28312912, year = {1987}, author = {Silertown, J}, title = {The evolution of hermaphroditism : An experimental test of the resource model.}, journal = {Oecologia}, volume = {72}, number = {1}, pages = {157-159}, doi = {10.1007/BF00385060}, pmid = {28312912}, issn = {1432-1939}, abstract = {Most plants are hermaphrodite (cosexual). Charnov et al. (1976) advanced the hypothesis that cosexuality is favoured in plants because a convex fitness set is generated by a non-additive relationship between male and female resource costs. In the first experimental test of this hypothesis, reproductive costs were measured in a male x female factorial design using male, female, cosexual, and neuter cucumber plants. Costs were measured by plant's vegetative growth response to treatments. The results show that male costs in the system used have negligible effect upon plant growth and female function, and imply a convex fitness set, in accordance with Charnov et al.'s model. Female function (fruit set) has an inhibitory effect upon vegetative growth and male flower production, favouring protandry.}, } @article {pmid26828222, year = {1986}, author = {Bernstein, IH and Teng, G and Garbin, CP}, title = {A Confirmatory Factoring of the Self-Consciousness Scale.}, journal = {Multivariate behavioral research}, volume = {21}, number = {4}, pages = {459-475}, doi = {10.1207/s15327906mbr2104_6}, pmid = {26828222}, issn = {0027-3171}, abstract = {Fenigstein, Scheier, and Buss (1975) developed a three subscale inventory designed to measure self-consciousness. Burnkrant and Page (1984) used confirmatory factor analysis to evaluate the scale and concluded that five items did not belong to their assigned scales and that one of the original subscales really measured two separable traits. Burnkrant and Page's conclusions may simply reflect incidental properties of the item statistics and could weaken the scale if adopted. Fenigstein et al.'s representation fits the data quite well in its original form. However, items on their social anxiety scale also tend to evoke relatively large variability over subjects and items on their public self-consciousness scale tend to evoke relatively little variability. In other words, items on their subscales differ nearly as much statistically as they do substantively.}, } @article {pmid25820009, year = {1985}, author = {Tzeng, OC and Everett, AV}, title = {A cross-cultural perspective of self-related conceptions in adolescence.}, journal = {International journal of psychology : Journal international de psychologie}, volume = {20}, number = {2}, pages = {329-348}, doi = {10.1080/00207598508247740}, pmid = {25820009}, issn = {0020-7594}, abstract = {Adolescence has been described as a transitional phase of life often involving turbulence, stress and strain in five major problem areas. Osgood et al.'s (1975) Atlas of Affective Meaning provided three basic measures of Evaluation, Potency and Activity for some 620 concepts that are representative of human life experiences in 30 language/culture communities around the world. The ratings of 30 concepts from the Atlas that represent the five major problem areas of adolescence were analyzed with the Three-Mode Multidimensional Scaling with Points-of-View Solution Technique (Tzeng and Landis 1978). The major results included the identification of cross-cultural common concept factors, 12 'idealized' cultural groups, and the factor structures of 12 'private' configurations. The concept structures that emerged from this study accurately recovered the problem areas of adolescence cited in the literature and also revealed unexpected homogeneities and differences in the cultures involved. Implications for government, social planning and education were discussed.}, } @article {pmid25306910, year = {2014}, author = {Shapiro, GK and Joyal-Desmarais, K and Perez, S and Rosberger, Z}, title = {A response to Fu et al.'s "Educational interventions to increase HPV vaccination acceptance".}, journal = {Vaccine}, volume = {32}, number = {48}, pages = {6342-6344}, doi = {10.1016/j.vaccine.2014.09.045}, pmid = {25306910}, issn = {1873-2518}, support = {288295//Canadian Institutes of Health Research/Canada ; }, mesh = {Female ; Health Promotion/*methods ; Humans ; Male ; Papillomavirus Vaccines/*therapeutic use ; *Patient Education as Topic ; Vaccination/*statistics & numerical data ; }, abstract = {This commentary is a response to a systematic review, recently published in Vaccine, which investigates the effectiveness of educational interventions in increasing uptake of the human papillomavirus vaccine. The systematic review by Fu et al. (2014) enhances the field's understanding of human papillomavirus vaccine interventions; however, their review contains a number of conceptual and methodological limitations. This commentary begins by addressing these limitations. We then address the importance of studying human papillomavirus vaccine interventions in diverse populations, and conclude by making recommendations for future research.}, } @article {pmid25302330, year = {2014}, author = {Lee, Y and Paik, J}, title = {Security analysis and improvement of an anonymous authentication scheme for roaming services.}, journal = {TheScientificWorldJournal}, volume = {2014}, number = {}, pages = {687879}, pmid = {25302330}, issn = {1537-744X}, mesh = {*Algorithms ; Cell Phone ; Computer Communication Networks ; *Computer Security ; *Computer Systems ; Humans ; Information Systems ; *Wireless Technology ; }, abstract = {An anonymous authentication scheme for roaming services in global mobility networks allows a mobile user visiting a foreign network to achieve mutual authentication and session key establishment with the foreign-network operator in an anonymous manner. In this work, we revisit He et al.'s anonymous authentication scheme for roaming services and present previously unpublished security weaknesses in the scheme: (1) it fails to provide user anonymity against any third party as well as the foreign agent, (2) it cannot protect the passwords of mobile users due to its vulnerability to an offline dictionary attack, and (3) it does not achieve session-key security against a man-in-the-middle attack. We also show how the security weaknesses of He et al.'s scheme can be addressed without degrading the efficiency of the scheme.}, } @article {pmid25257805, year = {2015}, author = {Gattinger, H and Stolt, M and Hantikainen, V and Köpke, S and Senn, B and Leino-Kilpi, H}, title = {A systematic review of observational instruments used to assess nurses' skills in patient mobilisation.}, journal = {Journal of clinical nursing}, volume = {24}, number = {5-6}, pages = {640-661}, doi = {10.1111/jocn.12689}, pmid = {25257805}, issn = {1365-2702}, mesh = {*Clinical Competence ; Humans ; Moving and Lifting Patients/*nursing ; *Observation ; Psychometrics ; }, abstract = {AIMS AND OBJECTIVES: The aim of this study was to identify and describe the existing observation instruments that are used to assess nurses' skills in patient mobilisation and to evaluate the psychometric properties of the included instruments.

BACKGROUND: Structured knowledge about instruments for assessing nurses' skills in patient mobilisation is limited.

DESIGN: Systematic review.

METHODS: Studies were identified via electronic database searches and reference lists and were included based on the eligibility criteria. Data regarding the type of instrument, the number of items/domains and the psychometric properties of the instruments were extracted, and the quality of the instruments were appraised according to Zwakhalen et al.'s (BMC Geriatrics, 2006) proposed criteria.

RESULTS: A total of 26 studies, reporting on 16 instruments, were included in this review. The instruments differed in terms of: (1) type of patient-mobilisation task, (2) focus of the instrument, (3) level of structure and (4) use by the observer. Most of the instruments were developed and used in evaluation studies that measured nurses' mobilisation techniques as an outcome of an educational intervention. The total quality score of the included instruments varied between 6-11 points out of a maximum quality score of 19.

CONCLUSION: Although patient mobilisation is part of nurses' everyday work, we suggest from the results of this review that no common consensus exists about the best way to perform patient-mobilisation tasks. The results from this study further show that no instrument measured all of the important aspects of effective patient mobilisation.

Most of the instruments that were reviewed were able to detect differences in patient-mobilisation techniques. However, convincing evidence is lacking with regard to the content, psychometric properties and practicability of these instruments for use in clinical practice. We suggest the development and validation of a new comprehensive instrument.}, } @article {pmid25238455, year = {2014}, author = {Marcus, DK and O'Connell, D and Norris, AL and Sawaqdeh, A}, title = {Is the Dodo bird endangered in the 21st century? A meta-analysis of treatment comparison studies.}, journal = {Clinical psychology review}, volume = {34}, number = {7}, pages = {519-530}, doi = {10.1016/j.cpr.2014.08.001}, pmid = {25238455}, issn = {1873-7811}, mesh = {Adult ; Cognitive Behavioral Therapy/*statistics & numerical data ; *Data Interpretation, Statistical ; Female ; Humans ; Male ; Outcome Assessment, Health Care/*statistics & numerical data ; Randomized Controlled Trials as Topic/*statistics & numerical data ; }, abstract = {The Dodo bird hypothesis asserts that when bona fide treatments are compared they yield similar outcomes and this hypothesis is consistent with a common factors or contextual model of psychotherapy. Wampold et al. (1997), the most recent comprehensive meta-analysis to test the Dodo bird hypothesis, yielded consistent evidence of treatment equivalence. However, some of Wampold et al.'s analytic strategies, such as using multiple effect sizes from the same study and prioritizing long-term follow-up, may have obscured treatment differences. The current meta-analysis updated Wampold et al. by analyzing studies published in the subsequent 16 years (k=51). Separate effect sizes were calculated for primary outcomes versus secondary outcomes, at termination and follow-up. Contrary to the Dodo bird hypothesis, there was evidence of treatment differences for primary outcomes at termination. Furthermore, cognitive-behavioral treatments may be incrementally more effective than alternative treatments for primary outcomes. Consistent with the Dodo bird hypothesis, there was little evidence of treatment differences for the secondary outcomes at termination and follow-up. There are small, statistically significant differences between bona-fide treatments when the specific targets of those treatments are assessed, but not when secondary outcomes are assessed, providing mixed support for both specific factors and contextual models of psychotherapy.}, } @article {pmid25237002, year = {2014}, author = {Lai, JS and Cella, D and Beaumont, J}, title = {It's good to have a choice; now let's get more data: response to Armstrong et al.'s "response to Lai et al., development of a symptom index for patients with primary brain tumors".}, journal = {Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research}, volume = {17}, number = {6}, pages = {754-755}, doi = {10.1016/j.jval.2014.07.004}, pmid = {25237002}, issn = {1524-4733}, mesh = {Brain Neoplasms/*drug therapy/*psychology ; Female ; *Health Status Indicators ; Humans ; Male ; }, } @article {pmid25233373, year = {2014}, author = {Simpson, CL and Wojciechowski, R and Oexle, K and Murgia, F and Portas, L and Li, X and Verhoeven, VJ and Vitart, V and Schache, M and Hosseini, SM and Hysi, PG and Raffel, LJ and Cotch, MF and Chew, E and Klein, BE and Klein, R and Wong, TY and van Duijn, CM and Mitchell, P and Saw, SM and Fossarello, M and Wang, JJ and , and Polašek, O and Campbell, H and Rudan, I and Oostra, BA and Uitterlinden, AG and Hofman, A and Rivadeneira, F and Amin, N and Karssen, LC and Vingerling, JR and Döring, A and Bettecken, T and Bencic, G and Gieger, C and Wichmann, HE and Wilson, JF and Venturini, C and Fleck, B and Cumberland, PM and Rahi, JS and Hammond, CJ and Hayward, C and Wright, AF and Paterson, AD and Baird, PN and Klaver, CC and Rotter, JI and Pirastu, M and Meitinger, T and Bailey-Wilson, JE and Stambolian, D}, title = {Genome-wide meta-analysis of myopia and hyperopia provides evidence for replication of 11 loci.}, journal = {PloS one}, volume = {9}, number = {9}, pages = {e107110}, pmid = {25233373}, issn = {1932-6203}, support = {N01 HC095168/HL/NHLBI NIH HHS/United States ; ZIA EY000403/ImNIH/Intramural NIH HHS/United States ; R01 DK077510/DK/NIDDK NIH HHS/United States ; N01-DK-6-2204/DK/NIDDK NIH HHS/United States ; HHSN268200782096C/HG/NHGRI NIH HHS/United States ; N01 HC-95159/HC/NHLBI NIH HHS/United States ; ZIAEY000403//PHS HHS/United States ; N01 HC095166/HL/NHLBI NIH HHS/United States ; MC_U127584475/MRC_/Medical Research Council/United Kingdom ; R01 EY016379/EY/NEI NIH HHS/United States ; N02-HL-6-4278/HL/NHLBI NIH HHS/United States ; UL1 RR033176/RR/NCRR NIH HHS/United States ; CZB/4/710/CSO_/Chief Scientist Office/United Kingdom ; CZB/4/438/CSO_/Chief Scientist Office/United Kingdom ; U01 DK094176/DK/NIDDK NIH HHS/United States ; N01-HC-95162/HC/NHLBI NIH HHS/United States ; UL1RR033176/RR/NCRR NIH HHS/United States ; UL1TR000124/TR/NCATS NIH HHS/United States ; N01 HC095161/HL/NHLBI NIH HHS/United States ; N01 HC095169/HL/NHLBI NIH HHS/United States ; Z99 EY999999/ImNIH/Intramural NIH HHS/United States ; RR-024156/RR/NCRR NIH HHS/United States ; N01-HC-95163/HC/NHLBI NIH HHS/United States ; N01-HC-95168/HC/NHLBI NIH HHS/United States ; Z01 EY000403/ImNIH/Intramural NIH HHS/United States ; UL1 RR024156/RR/NCRR NIH HHS/United States ; N01 HC095167/HL/NHLBI NIH HHS/United States ; R01-DK-077510/DK/NIDDK NIH HHS/United States ; 085475/B/08/Z/WT_/Wellcome Trust/United Kingdom ; K08 EY022943/EY/NEI NIH HHS/United States ; N01-HC-95165/HC/NHLBI NIH HHS/United States ; UL1 TR000114/TR/NCATS NIH HHS/United States ; UL1 TR000124/TR/NCATS NIH HHS/United States ; N01-HC-95169/HC/NHLBI NIH HHS/United States ; R01 EY020483/EY/NEI NIH HHS/United States ; R01EY020483/EY/NEI NIH HHS/United States ; N01-HC-95164/HC/NHLBI NIH HHS/United States ; N01-HC-95160/HC/NHLBI NIH HHS/United States ; MC_PC_U127561128/MRC_/Medical Research Council/United Kingdom ; N01 HC095163/HL/NHLBI NIH HHS/United States ; UL1 TR000142/TR/NCATS NIH HHS/United States ; N01-HC-95161/HC/NHLBI NIH HHS/United States ; /WT_/Wellcome Trust/United Kingdom ; N01 HC095162/HL/NHLBI NIH HHS/United States ; N01-HC-95166/HC/NHLBI NIH HHS/United States ; 085475/08/Z/WT_/Wellcome Trust/United Kingdom ; SRF/01/010/DH_/Department of Health/United Kingdom ; N01 HC095165/HL/NHLBI NIH HHS/United States ; N01 HC095164/HL/NHLBI NIH HHS/United States ; N01 HC095159/HC/NHLBI NIH HHS/United States ; N01-HC-95167/HC/NHLBI NIH HHS/United States ; R01EY016379/EY/NEI NIH HHS/United States ; N01 HC095160/HL/NHLBI NIH HHS/United States ; }, mesh = {Adult ; Age of Onset ; Aged ; Aged, 80 and over ; Alleles ; Eye/*physiopathology ; Female ; Genetic Association Studies ; Genetic Markers/genetics ; Genetic Predisposition to Disease ; Humans ; Hyperopia/*genetics ; Linkage Disequilibrium ; Male ; Middle Aged ; Myopia/*genetics ; Phenotype ; Polymorphism, Single Nucleotide ; White People/genetics ; }, abstract = {Refractive error (RE) is a complex, multifactorial disorder characterized by a mismatch between the optical power of the eye and its axial length that causes object images to be focused off the retina. The two major subtypes of RE are myopia (nearsightedness) and hyperopia (farsightedness), which represent opposite ends of the distribution of the quantitative measure of spherical refraction. We performed a fixed effects meta-analysis of genome-wide association results of myopia and hyperopia from 9 studies of European-derived populations: AREDS, KORA, FES, OGP-Talana, MESA, RSI, RSII, RSIII and ERF. One genome-wide significant region was observed for myopia, corresponding to a previously identified myopia locus on 8q12 (p = 1.25×10(-8)), which has been reported by Kiefer et al. as significantly associated with myopia age at onset and Verhoeven et al. as significantly associated to mean spherical-equivalent (MSE) refractive error. We observed two genome-wide significant associations with hyperopia. These regions overlapped with loci on 15q14 (minimum p value = 9.11×10(-11)) and 8q12 (minimum p value 1.82×10(-11)) previously reported for MSE and myopia age at onset. We also used an intermarker linkage- disequilibrium-based method for calculating the effective number of tests in targeted regional replication analyses. We analyzed myopia (which represents the closest phenotype in our data to the one used by Kiefer et al.) and showed replication of 10 additional loci associated with myopia previously reported by Kiefer et al. This is the first replication of these loci using myopia as the trait under analysis. "Replication-level" association was also seen between hyperopia and 12 of Kiefer et al.'s published loci. For the loci that show evidence of association to both myopia and hyperopia, the estimated effect of the risk alleles were in opposite directions for the two traits. This suggests that these loci are important contributors to variation of refractive error across the distribution.}, } @article {pmid25230463, year = {2014}, author = {Ye, JS and Reynolds, JF and Li, FM}, title = {A mechanistic-bioclimatic modeling analysis of the potential impact of climate change on biomes of the Tibetan Plateau.}, journal = {Ecology}, volume = {95}, number = {8}, pages = {2109-2120}, doi = {10.1890/13-1014.1}, pmid = {25230463}, issn = {0012-9658}, mesh = {*Climate Change ; *Ecosystem ; Environmental Monitoring ; Tibet ; }, abstract = {The Tibetan Plateau (TP) is experiencing high rates of climatic change. We present a novel combined mechanistic-bioclimatic modeling approach to determine how changes in precipitation and temperature on the TP may impact net primary production (NPP) in four major biomes (forest, shrub, grass, desert) and if there exists a maximum rain use efficiency (RUE(MAX)) that represents Huxman et al.'s "boundary that constrain[s] site-level productivity and efficiency." We used a daily mechanistic ecosystem model to generate 40-yr outputs using observed climatic data for scenarios of decreased precipitation (25-100%); increased air temperature (1 degrees - 6 degrees C); simultaneous changes in both precipitation (+/- 50%, +/- 25%) and air temperature (+1 to +6 degrees C) and increased interannual variability (IAV) of precipitation (+1 sigma to +3 sigma, with fixed means, where sigma is SD). We fitted model output from these scenarios to Huxman et al.'s RUE(MAX) bioclimatic model, NPP = alpha + RUE x PPT (where alpha is the intercept, RUE is rain use efficiency, and PPT is annual precipitation). Based on these analyses, we conclude that there is strong support (when not explicit, then trend-wise) for Huxman et al.'s assertion that biomes converge to a common RUE(MAX) during the driest years at a site, thus representing the boundary for highest rain use efficiency; the interactive effects of simultaneously decreasing precipitation and increasing temperature on NPP for the TP is smaller than might be expected from additive, single-factor changes in these drivers; and that increasing IAV of precipitation may ultimately have a larger impact on biomes of the Tibetan Plateau than changing amounts of rainfall and air temperature alone.}, } @article {pmid25200276, year = {2014}, author = {Sauto Arce, R and De Ormijana, AS and Orueta, JF and Gagnon, MP and Nuño-Solinís, R}, title = {A qualitative study on clinicians' perceptions about the implementation of a population risk stratification tool in primary care practice of the Basque health service.}, journal = {BMC family practice}, volume = {15}, number = {}, pages = {150}, pmid = {25200276}, issn = {1471-2296}, mesh = {*Advanced Practice Nursing ; *Attitude of Health Personnel ; Female ; Focus Groups ; *General Practitioners ; Humans ; Male ; Primary Health Care/*methods ; Qualitative Research ; Risk Assessment/*methods ; Spain ; }, abstract = {BACKGROUND: A prospective Population Risk Stratification (PRS) tool was first introduced in the public Basque Health Service in 2011, at the level of its several Primary Care (PC) practices. This paper aims at exploring the new tool's implementation process, as experienced by its potential adopters/users, ie. PC clinicians (doctors and nurses). Findings could help guide future PRS implementation strategies.

METHODS: Three focus groups exploring clinicians' opinions and experiences related to the PRS tool and its implementation in their daily practice were conducted. A purposive sample of 12 General Practitioners and 11 PC nurses participated in the groups. Discussions were digitally recorded, transcribed verbatim and analysed by two independent researchers using thematic analysis based on Graham et al.'s Knowledge Translation Theory.

RESULTS: Exploring PC clinicians' experience with the new PRS tool, allowed us to identify certain elements working as barriers and facilitators in its implementation process. This series of closely interrelated elements, which emerged as relevant in building up the complex implementation process of the new tool, as experienced by the clinicians, can be grouped into four domains: 1) clinicians' characteristics as potential adopters, 2) clinicians' perceptions of their practice settings where PRS is to implemented, 3) clinicians' perceptions of the tool, and 4) the implementation strategy used by the PRS promoter.

CONCLUSIONS: Lessons from the implementation process under study point at the need to frame the implementation of a new PRS tool within a wider strategy encouraging PC clinicians to orientate their daily practice towards a population health approach. The PRS tool could also improve the perceived utility by its potential adopters, by bringing it closer to the clinicians' needs and practice, and allowing it to become context-sensitive. This would require clinicians being involved from the earliest phases of conceptualisation, design and implementation of the new tool, and mounting efforts to improve communication between clinicians and tool promoters.Graham et al.'s Knowledge Translation Theory proved a suitable framework to explore the implementation process of a new PRS tool in the public Basque Health Service's PC practice, and hence to identify implementation barriers and facilitators as experienced by the clinicians.}, } @article {pmid25198782, year = {2015}, author = {Shalev, I and Bargh, J}, title = {On the association between loneliness and physical warmth-seeking through bathing: reply to Donnellan et al. (2014) and three further replications of Bargh and Shalev (2012) study 1.}, journal = {Emotion (Washington, D.C.)}, volume = {15}, number = {1}, pages = {120-123}, doi = {10.1037/emo0000014}, pmid = {25198782}, issn = {1931-1516}, mesh = {Emotions/*physiology ; Female ; Humans ; Loneliness/*psychology ; Male ; *Psychological Distance ; *Social Perception ; Thermosensing/*physiology ; }, abstract = {[Correction Notice: An Erratum for this article was reported in Vol 15(1) of Emotion (see record 2015-05076-005). In the article, there was an error in the abstract. The name of author Donnellan was misspelled as Donellan.] [Correction Notice: An Erratum for this article was reported in Vol 15(1) of Emotion (see record 2015-05076-004). In the article, the wrong supplemental file was originally posted. The correct file has now been posted.] As Tversky and Kahneman (1971) noted, effect sizes in smaller samples are inherently unstable. Donnellan [corrected] et al. (2014) in a large sample show that the relation between trait loneliness and warmth extraction through bathing activities is much smaller than in our initial smaller samples. We report further replications of our original findings in samples from India, Israel, and North America, again showing significant correlations between loneliness and physical warmth extraction from bathing and showering; the overall effect being reliable across all three samples, although, consistent with Donnellan [corrected] et al.'s conclusions, smaller than in our original studies. We also respond to criticisms of the original data analyses, noting that removal of the problematic 'bathing frequency' item from the warmth index did not substantially change the results and thus our conclusions from them. We also note that in their 2 studies in which Donnellan [corrected] et al. attempted to most closely follow our original procedure, they did replicate our original results, but not in the other 7 studies in which considerable procedural changes were made. As our new replications reveal variability in bathing and showering preferences and habits around the world, we recommend the inclusion of a wider sample of cultures beyond North American in future research. This research should also focus not only on the narrower question of how loneliness relates to bathing activities but on the broader relation between feelings of social coldness (e.g., after rejection or exclusion) and the seeking of physical warmth (e.g., warm food and drink, thermostat settings).}, } @article {pmid25185103, year = {2014}, author = {D'Amico, AV}, title = {Reply to K. Quan et Al, S.P. Collins et al, C.R. King et al, s. Arcangeli et al, d.B. Fuller, and D. Vordermark.}, journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology}, volume = {32}, number = {30}, pages = {3457}, doi = {10.1200/JCO.2014.57.6116}, pmid = {25185103}, issn = {1527-7755}, mesh = {Humans ; Male ; Prostatic Neoplasms/*radiotherapy/*surgery ; }, } @article {pmid25185090, year = {2014}, author = {Yu, JB and Cramer, LD and Herrin, J and Soulos, PR and Potosky, AL and Gross, CP}, title = {Reply to K. Quan et al, S.p. Collins et al, C.R. King et al, S. Arcangeli et Al, D.B. Fuller, and D. Vordermark.}, journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology}, volume = {32}, number = {30}, pages = {3456-3457}, doi = {10.1200/JCO.2014.57.6108}, pmid = {25185090}, issn = {1527-7755}, support = {P30 CA051008/CA/NCI NIH HHS/United States ; KL2 TR000140/TR/NCATS NIH HHS/United States ; R01CA149045/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; Male ; Prostatic Neoplasms/*radiotherapy/*surgery ; }, } @article {pmid25182326, year = {2014}, author = {Whatmore, AM}, title = {Ancient-pathogen genomics: coming of age?.}, journal = {mBio}, volume = {5}, number = {5}, pages = {e01676-14}, pmid = {25182326}, issn = {2150-7511}, mesh = {Brucella melitensis/*genetics ; Genome, Bacterial/*genetics ; Metagenomics/*methods ; }, abstract = {The potentially debilitating zoonotic disease brucellosis is thought to have been a scourge of mankind throughout history. New work by Kay et al. [mBio 5(4):e01337-14, 2014] adds to evidence for this by exploiting the huge advances in next-generation sequencing technology and applying shotgun metagenomics to a calcified nodule obtained from a 14th-century skeleton from Sardinia. While not the first DNA-based confirmation of Brucella in medieval DNA samples, Kay et al.'s study goes much further than previous reports based on single gene fragments in that it allows a full-genome reconstruction and thus facilitates meaningful comparative analysis of relationships with extant Brucella strains. These analyses confirm the close relationship of the genome to contemporary isolates from the western Mediterranean, illustrating the continuity of this lineage in the region over centuries. The study, along with recent studies characterizing other ancient-pathogen genomes, confirms that shotgun metagenomics offers us a powerful tool to fully characterize pathogens from ancient samples. Such studies promise to revolutionize our understanding of the nature of infectious disease in these materials and of the wider picture of the emergence, evolution, and spread of bacterial pathogens over history.}, } @article {pmid25180805, year = {2014}, author = {Gildersleeve, K and Haselton, MG and Fales, MR}, title = {Meta-analyses and p-curves support robust cycle shifts in women's mate preferences: reply to Wood and Carden (2014) and Harris, Pashler, and Mickes (2014).}, journal = {Psychological bulletin}, volume = {140}, number = {5}, pages = {1272-1280}, doi = {10.1037/a0037714}, pmid = {25180805}, issn = {1939-1455}, mesh = {Female ; Humans ; Male ; Ovulation/*physiology/*psychology ; Sexual Behavior/*psychology ; Sexual Partners/*psychology ; }, abstract = {Two meta-analyses evaluated shifts across the ovulatory cycle in women's mate preferences but reported very different findings. In this journal, we reported robust evidence for the pattern of cycle shifts predicted by the ovulatory shift hypothesis (Gildersleeve, Haselton, & Fales, 2014). However, Wood, Kressel, Joshi, and Louie (2014) claimed an absence of compelling support for this hypothesis and asserted that the few significant cycle shifts they observed were false positives resulting from publication bias, p-hacking, or other research artifacts. How could 2 meta-analyses of the same literature reach such different conclusions? We reanalyzed the data compiled by Wood et al. These analyses revealed problems in Wood et al.'s meta-analysis-some of which are reproduced in Wood and Carden's (2014) comment in the current issue of this journal-that led them to overlook clear evidence for the ovulatory shift hypothesis in their own set of effects. In addition, we present right-skewed p-curves that directly contradict speculations by Wood et al.; Wood and Carden; and Harris, Pashler, and Mickes (2014) that supportive findings in the cycle shift literature are false positives. Therefore, evidence from both of the meta-analyses and the p-curves strongly supports genuine, robust effects consistent with the ovulatory shift hypothesis and contradicts claims that these effects merely reflect publication bias, p-hacking, or other research artifacts. Unfounded speculations about p-hacking distort the research record and risk unfairly damaging researchers' reputations; they should therefore be made only on the basis of firm evidence.}, } @article {pmid25180804, year = {2014}, author = {Wood, W and Carden, L}, title = {Elusiveness of menstrual cycle effects on mate preferences: comment on Gildersleeve, Haselton, and Fales (2014).}, journal = {Psychological bulletin}, volume = {140}, number = {5}, pages = {1265-1271}, doi = {10.1037/a0036722}, pmid = {25180804}, issn = {1939-1455}, mesh = {Female ; Humans ; Male ; Ovulation/*physiology/*psychology ; Sexual Behavior/*psychology ; Sexual Partners/*psychology ; }, abstract = {This comment uses meta-analytic techniques to reconcile the apparent conflict between Gildersleeve, Haselton, and Fales's (2014) conclusion of "robust" effects of menstrual cycles on women's preferences for men of purported genetic quality and Wood, Kressel, Joshi, and Louie's (2014) assessment that the few, limited effects in this literature appear to be research artifacts. Despite these divergent conclusions, the literature in both reviews shows a broad distribution of effects, with fully one third of findings countering evolutionary psychology predictions. We demonstrate that Gildersleeve et al.'s conclusions were influenced by a small minority of supportive studies. Furthermore, we show that in both reviews, these supportive studies used imprecise estimates of women's cycle phase by failing to validate cycle day (e.g., with hormonal tests) or by including a large number of days in the fertile phase. More recently, as published studies have used more precise methods to estimate menstrual phase, the effect has declined to zero. Additionally, publication status proved important in both reviews, with published but not unpublished studies showing the predicted effects. In general, the limited evidence for evolutionary psychology predictions calls for more sophisticated models of hormonal processes in human mating.}, } @article {pmid25168990, year = {2014}, author = {El Ansari, W and Dibba, E and Labeeb, S and Stock, C}, title = {Body image concern and its correlates among male and female undergraduate students at Assuit University in Egypt.}, journal = {Global journal of health science}, volume = {6}, number = {5}, pages = {105-117}, pmid = {25168990}, issn = {1916-9736}, mesh = {Adolescent ; Body Image/*psychology ; Cross-Sectional Studies ; Depression/epidemiology ; Diet ; Egypt ; Exercise ; Female ; Health Behavior ; Humans ; Life Style ; Male ; *Mental Health ; Perception ; *Quality of Life ; Smoking/epidemiology ; Stress, Psychological/epidemiology ; Students/*psychology ; *Universities ; Young Adult ; }, abstract = {INTRODUCTION: This cross-sectional study examined variables associated with body image concern (BIC) and whether these associations differed between female and male students in Egypt. During the period 2009-2010, 3271 undergraduate students (1663 females, 1504 males) at Assuit University in Egypt completed a self-administered questionnaire that assessed BIC and other socio-demographic and health related variables.

METHODS: Based on Cooper et al.'s Body Shape Questionnaire the authors categorized BIC into 'no BIC'; 'mild BIC'; and 'moderate/marked BIC'. Multifactorial linear regression analysis examined the association between BIC and BMI, body image perception, lifestyle (physical activity, nutrition, smoking) and mental well-being variables (quality of life, finances-related stress, perceived stress, perceived health, depressive symptoms).

RESULTS: About 40% of the female students and 25.6% of male students reported having mild to marked BIC. The correlates of BIC did not exhibit striking differences between male and female students. For both genders, BIC was positively associated with BMI, body image perception as being too fat and with depressive symptoms. Self-rated health was inversely associated with BIC.

CONCLUSION: These findings suggest that health promoting strategies should address the co-occurrence of depressive symptoms and BIC, and should furthermore pay due attention to higher prevalence of BIC among female students.}, } @article {pmid25162880, year = {2014}, author = {Rottschaefer, WA}, title = {Is the science of positive intentional change a science of objective moral values?.}, journal = {The Behavioral and brain sciences}, volume = {37}, number = {4}, pages = {435-436}, doi = {10.1017/S0140525X13003269}, pmid = {25162880}, issn = {1469-1825}, mesh = {*Behavioral Sciences ; *Behaviorism ; *Cultural Evolution ; Humans ; }, abstract = {I examine whether Wilson et al.'s argument for a science of positive intentional change constitutes an argument for a science of objective moral values. Drawing from their discussion, I present four reasons for thinking that it may be and some considerations on why it may not be. Concluding, I seek help from the authors.}, } @article {pmid25162878, year = {2014}, author = {Peschl, MF and Fundneider, T}, title = {Evolving the future by learning from the future (as it emerges)? Toward an epistemology of change.}, journal = {The Behavioral and brain sciences}, volume = {37}, number = {4}, pages = {433-434}, doi = {10.1017/S0140525X13003245}, pmid = {25162878}, issn = {1469-1825}, mesh = {*Behavioral Sciences ; *Behaviorism ; *Cultural Evolution ; Humans ; }, abstract = {At the core of Wilson et al.'s paper stands the question of intentional change. We propose to extend this notion by introducing concepts from the domains of innovation and knowledge creation. By going beyond their "acceptance and commitment therapy" approach we present a comprehensive framework for a theory of change culminating in the change strategy of "learning from the future as it emerges."}, } @article {pmid25162859, year = {2014}, author = {Aitken, KJ}, title = {Could Bertrand Russell's barber have bitten his own teeth? A problem of logic and definitions.}, journal = {The Behavioral and brain sciences}, volume = {37}, number = {4}, pages = {416-417}, doi = {10.1017/S0140525X13003300}, pmid = {25162859}, issn = {1469-1825}, mesh = {*Behavioral Sciences ; *Behaviorism ; *Cultural Evolution ; Humans ; }, abstract = {Guiding the positive evolution of behavior is an admirable goal. Wilson et al.'s arguments are based largely on studies of problem correction. The methodology is sound, but not the post hoc ergo procter hoc extrapolation. What is required is evidence that it can proactively generate positive change. The evolution of human behavior to date has been affected by many factors that include unmalleable and unpredicted environmental changes.}, } @article {pmid25157145, year = {2014}, author = {Brown, NJ and MacDonald, DA and Samanta, MP and Friedman, HL and Coyne, JC}, title = {A critical reanalysis of the relationship between genomics and well-being.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {111}, number = {35}, pages = {12705-12709}, pmid = {25157145}, issn = {1091-6490}, mesh = {Artifacts ; Epigenomics/*methods ; Genomics/*methods ; Humans ; Leukocytes/physiology ; Linear Models ; *Models, Psychological ; Models, Statistical ; Personal Satisfaction ; *Philosophy ; Psychometrics/*methods ; Transcription, Genetic ; }, abstract = {Fredrickson et al. [Fredrickson BL, et al. (2013) Proc Natl Acad Sci USA 110(33):13684-13689] claimed to have observed significant differences in gene expression related to hedonic and eudaimonic dimensions of well-being. Having closely examined both their claims and their data, we draw substantially different conclusions. After identifying some important conceptual and methodological flaws in their argument, we report the results of a series of reanalyses of their dataset. We first applied a variety of exploratory and confirmatory factor analysis techniques to their self-reported well-being data. A number of plausible factor solutions emerged, but none of these corresponded to Fredrickson et al.'s claimed hedonic and eudaimonic dimensions. We next examined the regression analyses that purportedly yielded distinct differential profiles of gene expression associated with the two well-being dimensions. Using the best-fitting two-factor solution that we identified, we obtained effects almost twice as large as those found by Fredrickson et al. using their questionable hedonic and eudaimonic factors. Next, we conducted regression analyses for all possible two-factor solutions of the psychometric data; we found that 69.2% of these gave statistically significant results for both factors, whereas only 0.25% would be expected to do so if the regression process was really able to identify independent differential gene expression effects. Finally, we replaced Fredrickson et al.'s psychometric data with random numbers and continued to find very large numbers of apparently statistically significant effects. We conclude that Fredrickson et al.'s widely publicized claims about the effects of different dimensions of well-being on health-related gene expression are merely artifacts of dubious analyses and erroneous methodology.}, } @article {pmid25153848, year = {2014}, author = {Amireault, S}, title = {Doing more than just acknowledging attrition at follow-up: a comment on Lu, Cheng, and Chen (2013).}, journal = {Psychological reports}, volume = {115}, number = {2}, pages = {419-426}, doi = {10.2466/03.PR0.115c19z5}, pmid = {25153848}, issn = {0033-2941}, mesh = {*Data Interpretation, Statistical ; Humans ; Research Design/*standards ; *Research Subjects ; }, abstract = {Lu, Cheng, and Chen (2013) faced one of the most common challenges encountered in longitudinal studies: follow-up attrition. Using a correlational prospective design, 464 volunteers completed a questionnaire that measured the constructs of the theory of planned behavior, and subsequently 154 of them provided physical activity data at a 6-month follow-up. The proportion of participants (66.8%) for whom the investigators were not able to gather information on the behavioral outcome at follow-up may reflect a form of selection bias that may affect both the validity and generalizability of study results. Lu, et al.'s (2013) study is used here to explore the implication of follow-up attrition on the results and inference, to review what information should be reported in a scientific paper in such situations, and to give practical tips to handle follow-up attrition.}, } @article {pmid25152881, year = {2014}, author = {Hambli, R}, title = {Connecting mechanics and bone cell activities in the bone remodeling process: an integrated finite element modeling.}, journal = {Frontiers in bioengineering and biotechnology}, volume = {2}, number = {}, pages = {6}, pmid = {25152881}, issn = {2296-4185}, abstract = {Bone adaptation occurs as a response to external loadings and involves bone resorption by osteoclasts followed by the formation of new bone by osteoblasts. It is directly triggered by the transduction phase by osteocytes embedded within the bone matrix. The bone remodeling process is governed by the interactions between osteoblasts and osteoclasts through the expression of several autocrine and paracrine factors that control bone cell populations and their relative rate of differentiation and proliferation. A review of the literature shows that despite the progress in bone remodeling simulation using the finite element (FE) method, there is still a lack of predictive models that explicitly consider the interaction between osteoblasts and osteoclasts combined with the mechanical response of bone. The current study attempts to develop an FE model to describe the bone remodeling process, taking into consideration the activities of osteoclasts and osteoblasts. The mechanical behavior of bone is described by taking into account the bone material fatigue damage accumulation and mineralization. A coupled strain-damage stimulus function is proposed, which controls the level of autocrine and paracrine factors. The cellular behavior is based on Komarova et al.'s (2003) dynamic law, which describes the autocrine and paracrine interactions between osteoblasts and osteoclasts and computes cell population dynamics and changes in bone mass at a discrete site of bone remodeling. Therefore, when an external mechanical stress is applied, bone formation and resorption is governed by cells dynamic rather than adaptive elasticity approaches. The proposed FE model has been implemented in the FE code Abaqus (UMAT routine). An example of human proximal femur is investigated using the model developed. The model was able to predict final human proximal femur adaptation similar to the patterns observed in a human proximal femur. The results obtained reveal complex spatio-temporal bone adaptation. The proposed FEM model gives insight into how bone cells adapt their architecture to the mechanical and biological environment.}, } @article {pmid25134046, year = {2015}, author = {Lambe, L and Hudson, A and Stewart, SH}, title = {Drinking motives and attentional bias to affective stimuli in problem and non-problem drinkers.}, journal = {Psychology of addictive behaviors : journal of the Society of Psychologists in Addictive Behaviors}, volume = {29}, number = {2}, pages = {312-316}, doi = {10.1037/adb0000021}, pmid = {25134046}, issn = {1939-1501}, mesh = {Adult ; Affect/*physiology ; Alcohol Drinking/*psychology ; Alcoholism/*psychology ; Attention/*physiology ; Female ; Humans ; Male ; Motivation/*physiology ; Young Adult ; }, abstract = {Problem drinking may reflect a maladaptive means of coping with negative emotions or enhancing positive emotions. Disorders with affective symptoms are often characterized by attentional biases for symptom-congruent emotionally valenced stimuli. Regarding addictions, coping motivated (CM) problem gamblers exhibit an attentional bias for negative stimuli, whereas enhancement motivated (EM) problem gamblers exhibit this bias for positive stimuli (Hudson, Jacques, & Stewart, 2013). We predicted that problem drinkers would show similar motive-congruent attentional biases. Problem and non-problem drinkers (n = 48 per group) completed an emotional orienting task measuring attentional biases to positive, negative, and neutral stimuli. As predicted, EM problem drinkers showed an attentional bias for positive information (i.e., reduced accuracy for positively cued trials). However, CM problem drinkers displayed a general distractibility (i.e., reduced accuracy, regardless of cue valence). The results add further support for Cooper et al.'s (1992) motivational model of alcohol use, and indicate potential motivation-matched intervention targets. (PsycINFO Database Record}, } @article {pmid25129830, year = {2014}, author = {Rice, MJ and Gravenstein, N and Morey, TE}, title = {Response to Al-Khabori M. et al.'s "validation of a non-invasive pulse CO-oximetry based hemoglobin estimation in normal blood donors," Transfusion and Apheresis Science 2013 Nov 4. Accurate enough for blood donors? Not so fast.}, journal = {Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis}, volume = {51}, number = {1}, pages = {83}, doi = {10.1016/j.transci.2014.02.027}, pmid = {25129830}, issn = {1473-0502}, mesh = {Carbon Monoxide/*chemistry ; Female ; Hemoglobins/*chemistry ; Humans ; Male ; Oximetry/*methods ; }, } @article {pmid25125212, year = {2014}, author = {Bryant, M and Ashton, L and Brown, J and Jebb, S and Wright, J and Roberts, K and Nixon, J}, title = {Systematic review to identify and appraise outcome measures used to evaluate childhood obesity treatment interventions (CoOR): evidence of purpose, application, validity, reliability and sensitivity.}, journal = {Health technology assessment (Winchester, England)}, volume = {18}, number = {51}, pages = {1-380}, doi = {10.3310/hta18510}, pmid = {25125212}, issn = {2046-4924}, support = {09/127/07/DH_/Department of Health/United Kingdom ; MC_U105960389/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Absorptiometry, Photon ; Body Mass Index ; Humans ; Outcome Assessment, Health Care/*methods/*standards ; Pediatric Obesity/*therapy ; Reproducibility of Results ; }, abstract = {BACKGROUND: Lack of uniformity in outcome measures used in evaluations of childhood obesity treatment interventions can impede the ability to assess effectiveness and limits comparisons across trials.

OBJECTIVE: To identify and appraise outcome measures to produce a framework of recommended measures for use in evaluations of childhood obesity treatment interventions.

DATA SOURCES: Eleven electronic databases were searched between August and December 2011, including MEDLINE; MEDLINE In-Process and Other Non-Indexed Citations; EMBASE; PsycINFO; Health Management Information Consortium (HMIC); Allied and Complementary Medicine Database (AMED); Global Health, Maternity and Infant Care (all Ovid); Cumulative Index to Nursing and Allied Health Literature (CINAHL) (EBSCOhost); Science Citation Index (SCI) [Web of Science (WoS)]; and The Cochrane Library (Wiley) - from the date of inception, with no language restrictions. This was supported by review of relevant grey literature and trial databases.

REVIEW METHODS: Two searches were conducted to identify (1) outcome measures and corresponding citations used in published childhood obesity treatment evaluations and (2) manuscripts describing the development and/or evaluation of the outcome measures used in the childhood intervention obesity evaluations. Search 1 search strategy (review of trials) was modelled on elements of a review by Luttikhuis et al. (Oude Luttikhuis H, Baur L, Jansen H, Shrewsbury VA, O'Malley C, Stolk RP, et al. Interventions for treating obesity in children. Cochrane Database Syst Rev 2009;1:CD001872). Search 2 strategy (methodology papers) was built on Terwee et al.'s search filter (Terwee CB, Jansma EP, Riphagen II, de Vet HCW. Development of a methodological PubMed search filter for finding studies on measurement properties of measurement instruments. Qual Life Res 2009;18:1115-23). Eligible papers were appraised for quality initially by the internal project team. This was followed by an external appraisal by expert collaborators in order to agree which outcome measures should be recommended for the Childhood obesity Outcomes Review (CoOR) outcome measures framework.

RESULTS: Three hundred and seventy-nine manuscripts describing 180 outcome measures met eligibility criteria. Appraisal of these resulted in the recommendation of 36 measures for the CoOR outcome measures framework. Recommended primary outcome measures were body mass index (BMI) and dual-energy X-ray absorptiometry (DXA). Experts did not advocate any self-reported measures where objective measurement was possible (e.g. physical activity). Physiological outcomes hold potential to be primary outcomes, as they are indicators of cardiovascular health, but without evidence of what constitutes a minimally importance difference they have remained as secondary outcomes (although the corresponding lack of evidence for BMI and DXA is acknowledged). No preference-based quality-of-life measures were identified that would enable economic evaluation via calculation of quality-adjusted life-years. Few measures reported evaluating responsiveness.

LIMITATIONS: Proposed recommended measures are fit for use as outcome measures within studies that evaluate childhood obesity treatment evaluations specifically. These may or may not be suitable for other study designs, and some excluded measures may be more suitable in other study designs.

CONCLUSIONS: The CoOR outcome measures framework provides clear guidance of recommended primary and secondary outcome measures. This will enhance comparability between treatment evaluations and ensure that appropriate measures are being used. Where possible, future work should focus on modification and evaluation of existing measures rather than development of tools de nova. In addition, it is recommended that a similar outcome measures framework is produced to support evaluation of adult obesity programmes.

FUNDING: The National Institute for Health Research Health Technology Assessment programme.}, } @article {pmid25123464, year = {2014}, author = {Ndibanje, B and Lee, HJ and Lee, SG}, title = {Security analysis and improvements of authentication and access control in the Internet of Things.}, journal = {Sensors (Basel, Switzerland)}, volume = {14}, number = {8}, pages = {14786-14805}, pmid = {25123464}, issn = {1424-8220}, mesh = {Algorithms ; Communication ; Computer Communication Networks/*instrumentation ; Computer Security/*instrumentation ; Humans ; Internet/*instrumentation ; Wireless Technology/*instrumentation ; }, abstract = {Internet of Things is a ubiquitous concept where physical objects are connected over the internet and are provided with unique identifiers to enable their self-identification to other devices and the ability to continuously generate data and transmit it over a network. Hence, the security of the network, data and sensor devices is a paramount concern in the IoT network as it grows very fast in terms of exchanged data and interconnected sensor nodes. This paper analyses the authentication and access control method using in the Internet of Things presented by Jing et al. (Authentication and Access Control in the Internet of Things. In Proceedings of the 2012 32nd International Conference on Distributed Computing Systems Workshops, Macau, China, 18-21 June 2012, pp. 588-592). According to our analysis, Jing et al.'s protocol is costly in the message exchange and the security assessment is not strong enough for such a protocol. Therefore, we propose improvements to the protocol to fill the discovered weakness gaps. The protocol enhancements facilitate many services to the users such as user anonymity, mutual authentication, and secure session key establishment. Finally, the performance and security analysis show that the improved protocol possesses many advantages against popular attacks, and achieves better efficiency at low communication cost.}, } @article {pmid25123455, year = {2014}, author = {Mishra, D and Srinivas, J and Mukhopadhyay, S}, title = {A secure and efficient chaotic map-based authenticated key agreement scheme for telecare medicine information systems.}, journal = {Journal of medical systems}, volume = {38}, number = {10}, pages = {120}, pmid = {25123455}, issn = {1573-689X}, mesh = {Access to Information ; *Computer Security ; Humans ; *Medical Informatics ; *Nonlinear Dynamics ; Telemedicine/*instrumentation ; }, abstract = {Advancement in network technology provides new ways to utilize telecare medicine information systems (TMIS) for patient care. Although TMIS usually faces various attacks as the services are provided over the public network. Recently, Jiang et al. proposed a chaotic map-based remote user authentication scheme for TMIS. Their scheme has the merits of low cost and session key agreement using Chaos theory. It enhances the security of the system by resisting various attacks. In this paper, we analyze the security of Jiang et al.'s scheme and demonstrate that their scheme is vulnerable to denial of service attack. Moreover, we demonstrate flaws in password change phase of their scheme. Further, our aim is to propose a new chaos map-based anonymous user authentication scheme for TMIS to overcome the weaknesses of Jiang et al.'s scheme, while also retaining the original merits of their scheme. We also show that our scheme is secure against various known attacks including the attacks found in Jiang et al.'s scheme. The proposed scheme is comparable in terms of the communication and computational overheads with Jiang et al.'s scheme and other related existing schemes. Moreover, we demonstrate the validity of the proposed scheme through the BAN (Burrows, Abadi, and Needham) logic.}, } @article {pmid25122719, year = {2015}, author = {Lee, HY and Lee, J and Kim, NK}, title = {Gender Differences in Health Literacy Among Korean Adults: Do Women Have a Higher Level of Health Literacy Than Men?.}, journal = {American journal of men's health}, volume = {9}, number = {5}, pages = {370-379}, doi = {10.1177/1557988314545485}, pmid = {25122719}, issn = {1557-9891}, mesh = {Asian People ; Cross-Sectional Studies ; Depression/epidemiology ; Educational Status ; Female ; *Health Literacy ; Humans ; Income ; Male ; Marital Status ; Middle Aged ; Republic of Korea/epidemiology ; Sampling Studies ; Sex Factors ; Surveys and Questionnaires ; }, abstract = {The role of gender in determining the level of health literacy in Korean adults is unclear. This study aimed to investigate the level of health literacy in Korean adults and identify factors associated with health literacy by gender. This study employed a cross-sectional survey design with a convenient sample of 585 community-dwelling Korean adults age19 years and older. Health literacy was measured by using eight items selected from Chew et al.'s 16-question self-reported health literacy measure. In accordance with Andersen's health behavior model, predisposing, enabling, and need factors were included in the multiple regression model. Women indicated a higher level of health literacy than men in understanding medical forms, directions on medication bottles, and written information offered by health care providers. Additionally, for Korean women, a higher level of health literacy was associated with attaining a higher education level and having a consistent place to receive care. Unmarried men and men who had higher self-rated health reported a higher level of health literacy compared with their counterparts. Lower level of depression and higher monthly income were significantly linked to a higher level of health literacy in both men and women. This study has established the importance of gender differences in health literacy and suggests gender-specific intervention may be warranted to reduce the existing gap in health literacy in both Korean men and women. Future research should replicate this study to confirm whether or not our finding is an international phenomenon.}, } @article {pmid25115950, year = {2015}, author = {Cooper, BC and Adib, F}, title = {An assessment of the usefulness of Kinesiograph as an aid in the diagnosis of TMD: a review of Manfredini et al.'s studies.}, journal = {Cranio : the journal of craniomandibular practice}, volume = {33}, number = {1}, pages = {46-66}, doi = {10.1179/2151090314Y.0000000010}, pmid = {25115950}, issn = {0886-9634}, mesh = {Dental Occlusion ; *Electromyography ; Humans ; Movement ; Temporomandibular Joint Disorders/*diagnosis/physiopathology/therapy ; Vertical Dimension ; }, abstract = {AIM: Performing a literature review of publications by Dr. Manfredini et al. related to their temporomandibular joint (TMJ) injection therapy outcome with conclusions on the clinical utility of computerized measurement devices used in the management of temporomandibular disorders (TMDs). In addition, reviewing their published opinion on an occlusion: TMD versus a biopsychosocial paradigm for TMD. Manfredini et al. authored an article published in the Journal of the American Dental Association (JADA) 2013, "An Assessment of the usefulness of jaw kinesiography in monitoring temporomandibular disorders," the most recent of 12 articles. In all studies, subjects received TMJ injections with an objective measurement outcome criterion; increased maximum mouth opening (MMO) and subjective symptom improvement of pain and chewing function. In the 2013 JADA article, the Mandibular Kinesiograph, referred to as KG, measured MMO before and after therapy. In 11 prior articles, all subject groups with limited mouth opening exhibited very significant increased MMO post-treatment, documenting treatment success using the same 2013 protocol. The 2013 study showed a 1·1 mm improved MMO, described as insignificant. The authors did not critique or explain the aberrant, skewed 2013 outcome data contrasted with their prior studies, which showed overwhelmingly significant increased MMO. Instead, they concluded that the MMO recording device was clinically useless. This motivated a literature review of the authors' TMD publications.

CONCLUSION: The publications by Manfredini et al. recognized proponents of the psychosocial model of TMD, including the 2013 article, appear to be part of a campaign denying an occlusion: TMD relationship and disparaging the specific computerized measurement devices and the dentists using them in the management of their TMD patients using neuromuscular occlusion dental treatment.}, } @article {pmid25102775, year = {2014}, author = {Kong, JD and Davis, W and Wang, H}, title = {Dynamics of a cholera transmission model with immunological threshold and natural phage control in reservoir.}, journal = {Bulletin of mathematical biology}, volume = {76}, number = {8}, pages = {2025-2051}, doi = {10.1007/s11538-014-9996-9}, pmid = {25102775}, issn = {1522-9602}, mesh = {Bacteriophages/*immunology ; Cholera/epidemiology/immunology/microbiology/*transmission ; Computer Simulation ; *Disease Outbreaks ; Humans ; Incidence ; *Models, Immunological ; Seasons ; Vibrio cholerae/*immunology ; Virus Shedding/immunology ; }, abstract = {Cholera remains epidemic and endemic in the world, causing thousands of deaths annually in locations lacking adequate sanitation and water infrastructure. Yet, its dynamics are still not fully understood. In this paper, we simplify and improve Jensen et al.'s model (PNAS 103:4652-4657, 2006) by incorporating a Minimum Infection Dose (MID) into the incidence term. We perform local stability analysis and provide bifurcation diagrams of the bacterial carrying capacity with or without shedding. Choosing parameters such that the endemic or epidemic equilibrium is unstable (as it is the case in reality), we observe numerically that for the bacterial carrying capacity (K) less than the MID (c), oscillating trajectories exist only in the microbial scale, whereas for K > c, they exist in both the microbial and population scales. In both cases, increasing pathogen shed rate ξ increases the amplitude of the trajectories and the period of the trajectories for those that are periodic. Our findings highlight the importance of the relationship among the shedding rates, K, MID, the maximum bacterial growth rate (r) and the features of the disease outbreak. In addition, we identified a region in the parameter space of our model that leads to chaotic behaviour. This could be used to explain the irregularity in the seasonal patterns of outbreaks amongst different countries, especially if the positive relationship between bacterial proliferation and temperature is considered.}, } @article {pmid25101907, year = {2015}, author = {Ho, PM and Cooper, AJ and Hall, PJ and Smillie, LD}, title = {Factor structure and construct validity of the temporal experience of pleasure scales.}, journal = {Journal of personality assessment}, volume = {97}, number = {2}, pages = {200-208}, doi = {10.1080/00223891.2014.940625}, pmid = {25101907}, issn = {1532-7752}, mesh = {Adolescent ; Adult ; Australia ; *Emotions ; Factor Analysis, Statistical ; Female ; Humans ; Male ; *Motivation ; *Pleasure ; Psychometrics ; Reproducibility of Results ; Students ; Surveys and Questionnaires ; United Kingdom ; Universities ; Young Adult ; }, abstract = {Feelings of pleasure felt in the moment of goal attainment (consummatory pleasure) are thought to be dissociable from feelings of desire connected with the motivated approach of goals (anticipatory pleasure). The Temporal Experience of Pleasure Scales (TEPS; Gard, Gard, Kring, & John, 2006) was developed to assess individual differences in these distinct processes. Recently, an independent evaluation of the psychometric characteristics of a Chinese-translated TEPS suggested a more complex factor structure (Chan et al., 2012). This study aimed to reexamine the factor structure and convergent and divergent validity of the TEPS in two previously unexamined multiethnic samples. University students in the United Kingdom (N = 294) completed the TEPS and university students in Australia (N = 295) completed the TEPS as well as a battery of conceptually related questionnaires. A confirmatory factor analysis of Gard et al.'s (2006) 2-factor model produced inadequate fit, which model-modification indexes suggested might be due to item cross-loadings. This issue was examined further using an exploratory factor analysis, which revealed a clear 2-factor solution despite cross-loadings among some items. Finally, mixed evidence for convergent-divergent validity was obtained, in terms of relationships between the TEPS and measures of anhedonia, approach-motivation, and positive emotion.}, } @article {pmid25093577, year = {2014}, author = {Kover, ST and Davidson, MM and Sindberg, HA and Ellis Weismer, S}, title = {Use of the ADOS for assessing spontaneous expressive language in young children with ASD: a comparison of sampling contexts.}, journal = {Journal of speech, language, and hearing research : JSLHR}, volume = {57}, number = {6}, pages = {2221-2233}, pmid = {25093577}, issn = {1558-9102}, support = {P30 HD003352/HD/NICHD NIH HHS/United States ; R01 DC007223/DC/NIDCD NIH HHS/United States ; T32 DC005359/DC/NIDCD NIH HHS/United States ; P30 HD03352/HD/NICHD NIH HHS/United States ; T32 DC05359/DC/NIDCD NIH HHS/United States ; R01 DC07223/DC/NIDCD NIH HHS/United States ; }, mesh = {Aphasia, Broca/*diagnosis/psychology ; Autism Spectrum Disorder/*complications ; *Child Language ; Child, Preschool ; Communication ; Female ; Humans ; *Language Tests ; Male ; Parent-Child Relations ; Recreation ; Speech Intelligibility ; Speech Production Measurement/*methods ; }, abstract = {PURPOSE: The current study compared the spontaneous expressive language of children with autism spectrum disorder (ASD) across multiple language sampling contexts: the Autism Diagnostic Observation Schedule (ADOS; Lord, Rutter, DiLavore, & Risi, 1999) and play with an examiner or parent.

METHOD: Participants were children with ASD (n = 63; 55 boys) with a mean age of 45 months (SD = 3.94, range = 37-53). The number of utterances produced; percentage of intelligible utterances; number of different words; mean length of utterance; and the number of requests, comments, and instances of turn-taking were calculated for the ADOS, examiner-child play, and parent-child play. Children were categorized into Tager-Flusberg et al.'s (2009) developmental language phases for each context.

RESULTS: Effects of sampling context were identified for all variables examined. The ADOS resulted in fewer utterances and lower structural and pragmatic language performance than examiner-child play and/or parent-child play. Categorization of children into language phases differed across contexts.

CONCLUSIONS: Use of the ADOS as a language sampling context may lead to underestimating the abilities of young children with ASD relative to play with an examiner or parent. Researchers and clinicians should be aware of context effects, particularly for assessments designed to observe autism symptoms.}, } @article {pmid25092719, year = {2014}, author = {Aspden, T and Bradshaw, SA and Playford, ED and Riazi, A}, title = {Quality-of-life measures for use within care homes: a systematic review of their measurement properties.}, journal = {Age and ageing}, volume = {43}, number = {5}, pages = {596-603}, doi = {10.1093/ageing/afu089}, pmid = {25092719}, issn = {1468-2834}, mesh = {Age Factors ; Aged ; Aging/*psychology ; Checklist ; Dementia/diagnosis/*psychology/therapy ; *Geriatric Assessment ; *Homes for the Aged/standards ; Humans ; *Nursing Homes/standards ; Quality Indicators, Health Care ; *Quality of Life ; Reproducibility of Results ; *Surveys and Questionnaires/standards ; }, abstract = {OBJECTIVE: the aims of this review were (i) to identify quality-of-life (QoL) measures which have had their measurement properties validated in people residing in care homes or nursing homes, and to critically compare and summarise these instruments and (ii) to make recommendations for measurement instruments.

METHODS: bibliographic databases PsycINFO, PubMed, Cochrane, CINAHL and Embase were searched for articles evaluating measurement properties of QoL instruments in people residing in care homes. Methodological quality of studies was assessed using the consensus-based standards for the selection of health measurement instruments checklist. Measurement properties of instruments were appraised using a systematic checklist.

RESULTS: the search strategy resulted in 3252 unique citations, of which 15 articles were included in this review. These articles assessed 13 instruments, 8 of which were dementia or Alzheimer specific instruments. The QUALIDEM, a dementia-specific observational instrument, had the widest array of information available on its measurement properties, which were mostly satisfactory. Most measurement instruments lacked information on hypotheses testing and content validity. Information on responsiveness and measurement error was not available for any instrument.

CONCLUSIONS: for people with dementia living in care homes, the QUALIDEM is recommended for measuring QoL. For residents without dementia, we recommend Kane et al.'s Psychosocial Quality of Life Domains questionnaire. Studies of higher methodological quality, assessing a wider range of measurement properties are needed to allow a more fully informed choice of QoL instrument.}, } @article {pmid25088551, year = {2014}, author = {Tittes, S and Kane, NC}, title = {The genomics of adaptation, divergence and speciation: a congealing theory.}, journal = {Molecular ecology}, volume = {23}, number = {16}, pages = {3938-3940}, doi = {10.1111/mec.12855}, pmid = {25088551}, issn = {1365-294X}, mesh = {*Biological Evolution ; *Genetic Speciation ; Genetics, Population/*methods ; *Models, Genetic ; }, abstract = {In this issue, Flaxman et al. () report the results of sophisticated whole-genome simulations of speciation with gene flow, enhancing our understanding of the process by building on previous single-locus, multilocus and analytical works. Their findings provide us with new insights about how genomes can diverge and the importance of statistical and chromosomal linkage in facilitating reproductive isolation. The authors characterize the conditions under which, even with high gene flow and weak divergent selection, reproductive isolation between populations can occur due to the emergent stochastic process of genomewide congealing, where numerous statistically or physically linked loci of small effect allow selection to limit effective migration rates. The initial congealing event can occur within a broad range conditions, and once initiated, the self-reinforcing process leads to rapid divergence and ultimately two reproductively isolated populations. Flaxman et al.'s () work is a valuable contribution to our understanding of speciation with gene flow and in making a more predictive field of evolutionary genomics and speciation.}, } @article {pmid25087011, year = {2015}, author = {Braithwaite, E and Gariépy, G and Wiens-Kinkaid, M and Elbejjani, M and Fuhrer, R}, title = {Re: Hjorthøj et al.'s article: risk of suicide according to level of psychiatric treatment: a nationwide nested case-control study, Soc Psychiatry Psychiatr Epidemiol. 2014.}, journal = {Social psychiatry and psychiatric epidemiology}, volume = {50}, number = {1}, pages = {165-166}, pmid = {25087011}, issn = {1433-9285}, mesh = {Female ; Humans ; Male ; Psychotherapy/*statistics & numerical data ; Suicide/*statistics & numerical data ; }, } @article {pmid25081825, year = {2014}, author = {Motallebi Zadeh, N and Mortazavi, SH and Khaki, S and Heidari, K and Karbasi, A and Ostad Rahimi, S}, title = {Bilateral tibial lengthening over the nail: our experience of 143 cases.}, journal = {Archives of orthopaedic and trauma surgery}, volume = {134}, number = {9}, pages = {1219-1225}, doi = {10.1007/s00402-014-2069-6}, pmid = {25081825}, issn = {1434-3916}, mesh = {Adolescent ; Adult ; Bone Lengthening/instrumentation/*methods ; *Bone Nails ; *Cosmetic Techniques/instrumentation ; Female ; Follow-Up Studies ; Humans ; *Internal Fixators ; Leg Length Inequality/*surgery ; Male ; Patient Satisfaction/statistics & numerical data ; Postoperative Complications/epidemiology ; Tibia/*surgery ; Treatment Outcome ; Young Adult ; }, abstract = {INTRODUCTION: Using lengthening over an intramedullary nail as a technique for cosmetic purposes improves the individuals' quality of life and provides more satisfactory results due to less external fixator period.

METHODS: This study reports a case series of 143 individuals who underwent bilateral tibial lengthening over an intramedullary nail for cosmetic purposes together with the review of parameters related to the surgery and complications. Level of satisfaction was measured with the standard visual analog scale at least 1 year after removal of external fixator.

RESULTS: In this study, mean (SD) age of patients was 26.6 (7.26) years. 85 (59.4%) participants were male and 58 (40.6%) were female. Mean end lengthening of all individuals was 6.65 cm. The mean external fixator period was 93.7 days. Complication rate was 0.74 per segment but it decreased to 0.45 when pin-tract infection was excluded. Complications were categorized based on Paley et al.'s classification as 129 problems, 85 obstacles and no sequelae. Interestingly, 44 (30.8%) individuals had no problem and obstacle.

CONCLUSIONS: Lengthening over an intramedullary nail provides bone formation in equal quality to that obtained by the conventional Ilizarov method, along with lower rate of complications. The large number of individuals involved in our study is a remarkable benefit which could be used as an appropriate sample to compare results for outcomes and complications.}, } @article {pmid25068585, year = {2014}, author = {Digdon, N and Powell, RA and Harris, B}, title = {Little Albert's alleged neurological impairment: Watson, Rayner, and historical revision.}, journal = {History of psychology}, volume = {17}, number = {4}, pages = {312-324}, doi = {10.1037/a0037325}, pmid = {25068585}, issn = {1093-4510}, mesh = {Behavioral Research/ethics/*history/standards ; Behaviorism/*history ; History, 20th Century ; Humans ; Infant ; Patient Selection/ethics ; }, abstract = {In 2012, Fridlund, Beck, Goldie, and Irons (2012) announced that "Little Albert"-the infant that Watson and Rayner used in their 1920 study of conditioned fear (Watson & Rayner, 1920)-was not the healthy child the researchers described him to be, but was neurologically impaired almost from birth. Fridlund et al. also alleged that Watson had committed serious ethical breaches in regard to this research. Our article reexamines the evidentiary bases for these claims and arrives at an alternative interpretation of Albert as a normal infant. In order to set the stage for our interpretation, we first briefly describe the historical context for the Albert study, as well as how the study has been construed and revised since 1920. We then discuss the evidentiary issues in some detail, focusing on Fridlund et al.'s analysis of the film footage of Albert, and on the context within which Watson and Rayner conducted their study. In closing, we return to historical matters to speculate about why historiographical disputes matter and what the story of neurologically impaired Albert might be telling us about the discipline of psychology today.}, } @article {pmid25056721, year = {2014}, author = {Schwagmeyer, PL}, title = {Partner switching can favour cooperation in a biological market.}, journal = {Journal of evolutionary biology}, volume = {27}, number = {9}, pages = {1765-1774}, doi = {10.1111/jeb.12455}, pmid = {25056721}, issn = {1420-9101}, mesh = {Animals ; Clutch Size ; Consummatory Behavior ; Female ; Fertility ; Male ; *Mating Preference, Animal ; Sex Ratio ; *Sparrows ; }, abstract = {Intraspecific cooperation and interspecific mutualisms can be promoted by mechanisms that reduce the frequency with which cooperative organisms are exploited by unhelpful partners. One such mechanism consists of changing partners after interacting with an uncooperative individual. I used McNamara et al.'s (Nature, 451, 2008, 189) partner switching model as a framework to examine whether this mechanism can select for increased cooperative investment by house sparrows (Passer domesticus) collaborating to rear offspring; previous research on this species has shown that substantial cooperative investments by both pair members are required to achieve high pay-offs from collaborating. I found that the poorer the outcome of a breeding attempt relative to the number of eggs the female invested, the greater the likelihood of partner switching. The incidence of partner switching changed seasonally, with peak switching coinciding with an increase in the number of alternative partners available to females. After females switched partners, their breeding outcomes rose to match those of females that remained with the same partner; this was not the case for males that switched partners. Consistent with the model's prediction, males in stable partnerships achieved over 25% higher than average reproductive success, which was attributable to both persistently good breeding outcomes and their older partners' high fecundity. These results provide empirical support for the hypothesis that partner switching favours increased cooperative investment levels, and they demonstrate that variation in the relative value of by-product benefits can enhance that process.}, } @article {pmid25037603, year = {2014}, author = {Furr, LA}, title = {Facial disfigurement stigma: a study of victims of domestic assaults with fire in India.}, journal = {Violence against women}, volume = {20}, number = {7}, pages = {783-798}, doi = {10.1177/1077801214543384}, pmid = {25037603}, issn = {1552-8448}, mesh = {Burns/*complications/psychology ; Domestic Violence/*psychology ; Evaluation Studies as Topic ; Facial Injuries/*psychology ; Female ; Focus Groups ; Humans ; India ; *Social Stigma ; Socioeconomic Factors ; Spouse Abuse/*psychology ; }, abstract = {In India, the incidence of fire attacks on women has risen dramatically. Although studies and media accounts describe how and why these attacks occur, no research has investigated the lives of survivors. Qualitative analysis of the texts of two focus groups of women scarred by domestic attacks by fire reveals that these women are heavily stigmatized. Using Yang et al.'s theory that stigma is a response to perceived threats to values of everyday life and feminist theory as guides, the study identified two patterns of moral threat related to disfigurement: (a) Disfigurement challenges values and practices of women's family roles, and (b) disfigurement threatens normative religious sensibilities.}, } @article {pmid25025083, year = {2014}, author = {Zhao, Z and Shi, W}, title = {On the security of a novel probabilistic signature based on bilinear square Diffie-Hellman problem and its extension.}, journal = {TheScientificWorldJournal}, volume = {2014}, number = {}, pages = {345686}, pmid = {25025083}, issn = {1537-744X}, mesh = {*Mathematical Concepts ; }, abstract = {Probabilistic signature scheme has been widely used in modern electronic commerce since it could provide integrity, authenticity, and nonrepudiation. Recently, Wu and Lin proposed a novel probabilistic signature (PS) scheme using the bilinear square Diffie-Hellman (BSDH) problem. They also extended it to a universal designated verifier signature (UDVS) scheme. In this paper, we analyze the security of Wu et al.'s PS scheme and UDVS scheme. Through concrete attacks, we demonstrate both of their schemes are not unforgeable. The security analysis shows that their schemes are not suitable for practical applications.}, } @article {pmid24999969, year = {2014}, author = {Corbani, AC and Hachey, MH and Desrochers, A}, title = {Food provisioning and parental status in songbirds: can occupancy models be used to estimate nesting performance?.}, journal = {PloS one}, volume = {9}, number = {7}, pages = {e101765}, pmid = {24999969}, issn = {1932-6203}, mesh = {Animals ; *Feeding Behavior ; *Food ; Forests ; *Models, Statistical ; *Nesting Behavior ; Probability ; Reproducibility of Results ; *Songbirds ; }, abstract = {Indirect methods to estimate parental status, such as the observation of parental provisioning, have been problematic due to potential biases associated with imperfect detection. We developed a method to evaluate parental status based on a novel combination of parental provisioning observations and hierarchical modeling. In the summers of 2009 to 2011, we surveyed 393 sites, each on three to four consecutive days at Forêt Montmorency, Québec, Canada. We assessed parental status of 2331 adult songbirds based on parental food provisioning. To account for imperfect detection of parental status, we applied MacKenzie et al.'s (2002) two-state hierarchical model to obtain unbiased estimates of the proportion of sites with successfully nesting birds, and the proportion of adults with offspring. To obtain an independent evaluation of detection probability, we monitored 16 active nests in 2010 and conducted parental provisioning observations away from them. The probability of detecting food provisioning was 0.31 when using nest monitoring, a value within the 0.11 to 0.38 range that was estimated by two-state models. The proportion of adults or sites with broods approached 0.90 and varied depending on date during the sampling season and year, exemplifying the role of eastern boreal forests as highly productive nesting grounds for songbirds. This study offers a simple and effective sampling design for studying avian reproductive performance that could be implemented in national surveys such as breeding bird atlases.}, } @article {pmid24997858, year = {2014}, author = {Li, CT and Lee, CC and Weng, CY}, title = {A secure chaotic maps and smart cards based password authentication and key agreement scheme with user anonymity for telecare medicine information systems.}, journal = {Journal of medical systems}, volume = {38}, number = {9}, pages = {77}, pmid = {24997858}, issn = {1573-689X}, mesh = {*Computer Security/instrumentation ; *Confidentiality ; *Electronic Health Records ; Humans ; *Information Systems/instrumentation ; Software Design ; *Telemedicine ; User-Computer Interface ; }, abstract = {Telecare medicine information system (TMIS) is widely used for providing a convenient and efficient communicating platform between patients at home and physicians at medical centers or home health care (HHC) organizations. To ensure patient privacy, in 2013, Hao et al. proposed a chaotic map based authentication scheme with user anonymity for TMIS. Later, Lee showed that Hao et al.'s scheme is in no provision for providing fairness in session key establishment and gave an efficient user authentication and key agreement scheme using smart cards, in which only few hashing and Chebyshev chaotic map operations are required. In addition, Jiang et al. discussed that Hao et al.'s scheme can not resist stolen smart card attack and they further presented an improved scheme which attempts to repair the security pitfalls found in Hao et al.'s scheme. In this paper, we found that both Lee's and Jiang et al.'s authentication schemes have a serious security problem in that a registered user's secret parameters may be intentionally exposed to many non-registered users and this problem causing the service misuse attack. Therefore, we propose a slight modification on Lee's scheme to prevent the shortcomings. Compared with previous schemes, our improved scheme not only inherits the advantages of Lee's and Jiang et al.'s authentication schemes for TMIS but also remedies the serious security weakness of not being able to withstand service misuse attack.}, } @article {pmid24994512, year = {2014}, author = {Xie, Q and Liu, W and Wang, S and Han, L and Hu, B and Wu, T}, title = {Improvement of a uniqueness-and-anonymity-preserving user authentication scheme for connected health care.}, journal = {Journal of medical systems}, volume = {38}, number = {9}, pages = {91}, pmid = {24994512}, issn = {1573-689X}, mesh = {Algorithms ; *Computer Communication Networks ; *Computer Security ; Confidentiality ; *Electronic Health Records ; Health Information Exchange ; Humans ; *Patient Identification Systems ; Software Design ; *User-Computer Interface ; }, abstract = {Patient's privacy-preserving, security and mutual authentication between patient and the medical server are the important mechanism in connected health care applications, such as telecare medical information systems and personally controlled health records systems. In 2013, Wen showed that Das et al.'s scheme is vulnerable to the replay attack, user impersonation attacks and off-line guessing attacks, and then proposed an improved scheme using biometrics, password and smart card to overcome these weaknesses. However, we show that Wen's scheme is still vulnerable to off-line password guessing attacks, does not provide user's anonymity and perfect forward secrecy. Further, we propose an improved scheme to fix these weaknesses, and use the applied pi calculus based formal verification tool ProVerif to prove the security and authentication.}, } @article {pmid24981373, year = {2015}, author = {Orsini, A and Pezzuti, L and Hulbert, S}, title = {Beyond the floor effect on the Wechsler Intelligence Scale for Children--4th Ed. (WISC-IV): calculating IQ and Indexes of subjects presenting a floored pattern of results.}, journal = {Journal of intellectual disability research : JIDR}, volume = {59}, number = {5}, pages = {468-473}, doi = {10.1111/jir.12150}, pmid = {24981373}, issn = {1365-2788}, mesh = {Adolescent ; Child ; Female ; Humans ; Intellectual Disability/*diagnosis ; Intelligence/*physiology ; Male ; Psychometrics/*methods ; Wechsler Scales/*statistics & numerical data ; }, abstract = {BACKGROUND: It is now widely known that children with severe intellectual disability show a 'floor effect' on the Wechsler scales. This effect emerges because the practice of transforming raw scores into scaled scores eliminates any variability present in participants with low intellectual ability and because intelligence quotient (IQ) scores are limited insofar as they do not measure scores lower than 40.

METHOD: Following Hessl et al.'s results, the present authors propose a method for the computation of the Wechsler Intelligence Scale for Children--4th Ed. (WISC-IV)'s IQ and Indexes in intellectually disabled participants affected by a floored pattern of results. The Italian standardization sample (n = 2200) for the WISC-IV was used. The method presented in this study highlights the limits of the 'floor effect' of the WISC-IV in children with serious intellectual disability who present a profile with weighted scores of 1 in all the subtests despite some variability in the raw scores.

RESULTS: Such method eliminates the floor effect of the scale and therefore makes it possible to analyse the strengths and weaknesses of the WISC-IV's Indexes in these participants.

CONCLUSIONS: The Authors reflect on clinical utility of this method and on the meaning of raw score of 0 on subtest.}, } @article {pmid24978134, year = {2014}, author = {Fergus, TA and Valentiner, DP and Kim, HS and McGrath, PB}, title = {The Social Interaction Anxiety Scale (SIAS) and the Social Phobia Scale (SPS): a comparison of two short-form versions.}, journal = {Psychological assessment}, volume = {26}, number = {4}, pages = {1281-1291}, doi = {10.1037/a0037313}, pmid = {24978134}, issn = {1939-134X}, mesh = {Adolescent ; Adult ; Aged ; Anxiety Disorders/*diagnosis ; Child ; Female ; Humans ; *Interpersonal Relations ; Male ; Middle Aged ; Phobic Disorders/diagnosis ; Psychiatric Status Rating Scales/*standards ; Psychometrics ; Reproducibility of Results ; Young Adult ; }, abstract = {The widespread use of Mattick and Clarke's (1998) Social Interaction Anxiety Scale (SIAS) and Social Phobia Scale (SPS) led 2 independent groups of researchers to develop short forms of these measures (Fergus, Valentiner, McGrath, Gier-Lonsway, & Kim, 2012; Peters, Sunderland, Andrews, Rapee, & Mattick, 2012). This 3-part study examined the psychometric properties of Fergus et al.'s and Peters et al.'s short forms of the SIAS and SPS using an American nonclinical adolescent sample in Study 1 (N = 98), American patient sample with an anxiety disorder in Study 2 (N = 117), and both a South Korean college student sample (N = 341) and an American college student sample (N = 550) in Study 3. Scores on both sets of short forms evidenced adequate internal consistency, interitem correlations, and measurement invariance. Scores on Fergus et al.'s short forms, particularly their SIAS short form, tended to capture more unique variance in scores of criterion measures than did scores on Peters et al.'s short forms. Implications for the use of these 2 sets of short forms are discussed.}, } @article {pmid24970451, year = {2014}, author = {Sedek, G and Kossowska, M and Rydzewska, K}, title = {The importance of adult life-span perspective in explaining variations in political ideology.}, journal = {The Behavioral and brain sciences}, volume = {37}, number = {3}, pages = {329-330}, doi = {10.1017/S0140525X13002732}, pmid = {24970451}, issn = {1469-1825}, mesh = {*Attitude ; Humans ; *Individuality ; *Models, Psychological ; Personality/*physiology ; *Politics ; }, abstract = {As a comment on Hibbing et al.'s paper, we discuss the evolution of political and social views from more liberal to more conservative over the span of adulthood. We show that Hibbing et al.'s theoretical model creates a false prediction from this developmental perspective, as increased conservatism in the adult life-span trajectory is accompanied by the avoidance of negative bias.}, } @article {pmid24970442, year = {2014}, author = {Ludeke, SG and DeYoung, CG}, title = {Differences in negativity bias probably underlie variation in attitudes toward change generally, not political ideology specifically.}, journal = {The Behavioral and brain sciences}, volume = {37}, number = {3}, pages = {319-320}, doi = {10.1017/S0140525X13002641}, pmid = {24970442}, issn = {1469-1825}, mesh = {*Attitude ; Humans ; *Individuality ; *Models, Psychological ; Personality/*physiology ; *Politics ; }, abstract = {Many of the characteristics cited in Hibbing et al.'s account are ineffective predictors of economic conservatism. However, these same characteristics are often associated with differences not only in social conservatism but also in religiousness and authoritarianism. Hibbing et al. may have offered a useful explanation of traditionalism and attitudes toward change across domains rather than of general political attitudes.}, } @article {pmid24970441, year = {2014}, author = {Lilienfeld, SO and Latzman, RD}, title = {Threat bias, not negativity bias, underpins differences in political ideology.}, journal = {The Behavioral and brain sciences}, volume = {37}, number = {3}, pages = {318-319}, doi = {10.1017/S0140525X1300263X}, pmid = {24970441}, issn = {1469-1825}, mesh = {*Attitude ; Humans ; *Individuality ; *Models, Psychological ; Personality/*physiology ; *Politics ; }, abstract = {Although disparities in political ideology are rooted partly in dispositional differences, Hibbing et al.'s analysis paints with an overly broad brush. Research on the personality correlates of liberal-conservative differences points not to global differences in negativity bias, but to differences in threat bias, probably emanating from differences in fearfulness. This distinction bears implications for etiological research and persuasion efforts.}, } @article {pmid24970436, year = {2014}, author = {Hogan, PC}, title = {Negativity bias, emotion targets, and emotion systems.}, journal = {The Behavioral and brain sciences}, volume = {37}, number = {3}, pages = {314-315}, doi = {10.1017/S0140525X13002586}, pmid = {24970436}, issn = {1469-1825}, mesh = {*Attitude ; Humans ; *Individuality ; *Models, Psychological ; Personality/*physiology ; *Politics ; }, abstract = {Hibbing et al.'s article isolates a plausible psychological factor contributing to differences in political orientation. However, there are two potential difficulties. Both the nature of negativity and the liberal-conservative opposition are ambiguous. A possible way of treating these problems enhances the theoretical framework through fuller reference to emotion systems and categories of triggers for those systems.}, } @article {pmid24967507, year = {2014}, author = {Renard, E and Boizel, R}, title = {Comments on Patel et al.'s "Randomized trial of infusion set function: steel versus teflon": early catheter failures may differ according to teflon catheter model.}, journal = {Diabetes technology & therapeutics}, volume = {16}, number = {8}, pages = {545-546}, doi = {10.1089/dia.2014.0058}, pmid = {24967507}, issn = {1557-8593}, mesh = {Diabetes Mellitus, Type 1/*drug therapy ; Female ; Humans ; Hypoglycemic Agents/*administration & dosage ; Infusions, Intravenous/*instrumentation ; Insulin/*administration & dosage ; Male ; *Monitoring, Physiologic ; *Polytetrafluoroethylene ; *Steel ; }, } @article {pmid24962980, year = {2014}, author = {Che, H and Lukas, C and Morel, J and Combe, B}, title = {Reply to Talarico et al.'s comment: "Rate of serious infections in patients with rheumatoid arthritis receiving tumor necrosis factor (TNF)-alpha antagonist: a prospective observational study".}, journal = {Joint bone spine}, volume = {81}, number = {4}, pages = {379-380}, doi = {10.1016/j.jbspin.2014.04.003}, pmid = {24962980}, issn = {1778-7254}, mesh = {Antirheumatic Agents/*adverse effects ; Arthritis, Rheumatoid/*drug therapy ; Herpesviridae Infections/*etiology ; Humans ; }, } @article {pmid24962910, year = {2014}, author = {Blum, LD}, title = {On: the problem of dichotomies: comment on Bohleber et al.'s (2013) article.}, journal = {The International journal of psycho-analysis}, volume = {95}, number = {3}, pages = {577-578}, doi = {10.1111/1745-8315.12191}, pmid = {24962910}, issn = {1745-8315}, mesh = {*Acting Out ; Humans ; *Psychoanalytic Theory ; Psychoanalytic Therapy/*methods ; *Transference, Psychology ; }, } @article {pmid24948583, year = {2014}, author = {Gao, J and Li, C and Feng, C and Xie, M and Yin, Y and Davatzikos, C}, title = {Non-locally regularized segmentation of multiple sclerosis lesion from multi-channel MRI data.}, journal = {Magnetic resonance imaging}, volume = {32}, number = {8}, pages = {1058-1066}, pmid = {24948583}, issn = {1873-5894}, support = {R01 EB009234/EB/NIBIB NIH HHS/United States ; }, mesh = {Algorithms ; Artificial Intelligence ; Automation ; Brain/pathology ; False Positive Reactions ; Fuzzy Logic ; Humans ; Image Processing, Computer-Assisted/*methods ; Magnetic Resonance Imaging/*methods ; Models, Statistical ; Multiple Sclerosis/*pathology ; Pattern Recognition, Automated/methods ; Reproducibility of Results ; Sensitivity and Specificity ; }, abstract = {Segmentation of multiple sclerosis (MS) lesion is important for many neuroimaging studies. In this paper, we propose a novel algorithm for automatic segmentation of MS lesions from multi-channel MR images (T1W, T2W and FLAIR images). The proposed method is an extension of Li et al.'s algorithm in [1], which only segments the normal tissues from T1W images. The proposed method is aimed to segment MS lesions, while normal tissues are also segmented and bias field is estimated to handle intensity inhomogeneities in the images. Another contribution of this paper is the introduction of a nonlocal means technique to achieve spatially regularized segmentation, which overcomes the influence of noise. Experimental results have demonstrated the effectiveness and advantages of the proposed algorithm.}, } @article {pmid24943682, year = {2014}, author = {Lin, J and Li, Z and Li, M and He, S}, title = {Letter regarding Wu JR et al.: S-1-based therapy versus S-1 monotherapy in advanced gastric cancer: a meta-analysis.}, journal = {Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine}, volume = {35}, number = {8}, pages = {7405}, pmid = {24943682}, issn = {1423-0380}, mesh = {Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Humans ; Oxonic Acid/*therapeutic use ; Stomach Neoplasms/*drug therapy ; Tegafur/*therapeutic use ; }, } @article {pmid24935627, year = {2014}, author = {Patterson, MM}, title = {Group typicality, group loyalty and cognitive development.}, journal = {The British journal of developmental psychology}, volume = {32}, number = {3}, pages = {252-254}, doi = {10.1111/bjdp.12051}, pmid = {24935627}, issn = {2044-835X}, mesh = {Child ; Child Development/*physiology ; Cognition/*physiology ; *Group Processes ; Humans ; *Social Behavior ; *Social Perception ; }, abstract = {Over the course of childhood, children's thinking about social groups changes in a variety of ways. Developmental Subjective Group Dynamics (DSGD) theory emphasizes children's understanding of the importance of conforming to group norms. Abrams et al.'s study, which uses DSGD theory as a framework, demonstrates the social cognitive skills underlying young elementary school children's thinking about group norms. Future research on children's thinking about groups and group norms should explore additional elements of this topic, including aspects of typicality beyond loyalty.}, } @article {pmid24934417, year = {2014}, author = {Gyekye, SA and Haybatollahi, M}, title = {Relationship between organizational justice and organizational safety climate: do fairness perceptions influence employee safety behaviour?.}, journal = {International journal of occupational safety and ergonomics : JOSE}, volume = {20}, number = {2}, pages = {199-211}, doi = {10.1080/10803548.2014.11077045}, pmid = {24934417}, issn = {1080-3548}, mesh = {Accidents, Occupational/prevention & control ; Attitude ; Female ; Ghana ; Humans ; Job Satisfaction ; Male ; *Occupational Health ; Organizational Culture ; *Safety Management ; }, abstract = {This study investigated the relationships between organizational justice, organizational safety climate, job satisfaction, safety compliance and accident frequency. Ghanaian industrial workers participated in the study (N = 320). Safety climate and justice perceptions were assessed with Hayes, Parender, Smecko, et al.'s (1998) and Blader and Tyler's (2003) scales respectively. A median split was performed to dichotomize participants into 2 categories: workers with positive and workers with negative justice perceptions. Confirmatory factors analysis confirmed the 5-factor structure of the safety scale. Regression analyses and t tests indicated that workers with positive fairness perceptions had constructive perspectives regarding workplace safety, expressed greater job satisfaction, were more compliant with safety policies and registered lower accident rates. These findings provide evidence that the perceived level of fairness in an organization is closely associated with workplace safety perception and other organizational factors which are important for safety. The implications for safety research are discussed.}, } @article {pmid24919642, year = {2014}, author = {Denis, F}, title = {Response to Andrea Tendas et al.'s making quality of life assessment a dashboard for patients management.}, journal = {Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer}, volume = {22}, number = {9}, pages = {2313}, pmid = {24919642}, issn = {1433-7339}, mesh = {*Diagnostic Self Evaluation ; Female ; Humans ; Lung Neoplasms/*diagnosis ; Male ; Neoplasm Recurrence, Local/*diagnosis ; }, } @article {pmid24919012, year = {2014}, author = {Choi, Y and Lee, D and Kim, J and Jung, J and Nam, J and Won, D}, title = {Security enhanced user authentication protocol for wireless sensor networks using elliptic curves cryptography.}, journal = {Sensors (Basel, Switzerland)}, volume = {14}, number = {6}, pages = {10081-10106}, pmid = {24919012}, issn = {1424-8220}, abstract = {Wireless sensor networks (WSNs) consist of sensors, gateways and users. Sensors are widely distributed to monitor various conditions, such as temperature, sound, speed and pressure but they have limited computational ability and energy. To reduce the resource use of sensors and enhance the security of WSNs, various user authentication protocols have been proposed. In 2011, Yeh et al. first proposed a user authentication protocol based on elliptic curve cryptography (ECC) for WSNs. However, it turned out that Yeh et al.'s protocol does not provide mutual authentication, perfect forward secrecy, and key agreement between the user and sensor. Later in 2013, Shi et al. proposed a new user authentication protocol that improves both security and efficiency of Yeh et al.'s protocol. However, Shi et al.'s improvement introduces other security weaknesses. In this paper, we show that Shi et al.'s improved protocol is vulnerable to session key attack, stolen smart card attack, and sensor energy exhausting attack. In addition, we propose a new, security-enhanced user authentication protocol using ECC for WSNs.}, } @article {pmid24899147, year = {2015}, author = {Kim, MJ and Kim, MS}, title = {Persistent primitive trigeminal artery: analysis of anatomical characteristics and clinical significances.}, journal = {Surgical and radiologic anatomy : SRA}, volume = {37}, number = {1}, pages = {69-74}, pmid = {24899147}, issn = {1279-8517}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Anatomic Variation ; Basilar Artery/*anatomy & histology/diagnostic imaging ; Carotid Artery, Internal/*anatomy & histology/diagnostic imaging ; Cerebral Angiography ; *Cerebrovascular Circulation ; Child ; Female ; Humans ; Magnetic Resonance Angiography ; Male ; Middle Aged ; Young Adult ; }, abstract = {PURPOSE: The purpose of this study was to evaluate the classification of persistent primitive trigeminal artery (PPTA) based on computed tomography (CT) angiography, magnetic resonance (MR) angiography, and cerebral angiography and to review the clinical significance.

MATERIALS AND METHODS: Images obtained by CT angiography performed between January 2011 and August 2013, MR angiography between January 2005 and January 2013, and cerebral angiography between January 2003 and November 2012 were analyzed for the presence of a PPTA. The diagnostic criterion for a PPTA was an artery that arises from the cavernous internal carotid artery and then joins the basilar artery (BA). We classified each PPTA by two different methods. First, the PPTA was classified as type 1, 2, 3, or 4 according to Weon et al.'s classification. Second, the classification of the PPTA was also made according to Salas et al.'s proposal, as a medial or lateral type.

RESULTS: Eighteen of 8,900 patients (0.2%) had a PPTA. Of all 18 patients with a PPTA, nine were classified as type 1, two as type 2, six as type 3, and one as type 4. Seventeen PPTAs were a lateral type, and one was a medial type. Regarding the degree of BA hypoplasia, no hypoplasia was seen in six cases, moderate hypoplasia was identified in six cases, and severe hypoplasia was seen in six cases.

CONCLUSIONS: This study revealed four types of PPTA according to Weon et al.'s classification. The presence of a PPTA should be considered by both the clinician and the radiologist who interprets the CT angiography, MR angiography, and conventional angiograms.}, } @article {pmid24885265, year = {2014}, author = {Ertl, V and Neuner, F}, title = {Are school-based mental health interventions for war-affected children effective and harmless?.}, journal = {BMC medicine}, volume = {12}, number = {}, pages = {84}, pmid = {24885265}, issn = {1741-7015}, mesh = {Female ; Humans ; Male ; }, abstract = {In recent years, different approaches to large-scale mental health service provision for children in war-affected, mainly low- and middle-income, countries have been developed. Some school-based programs aiming at both strengthening resilience and reducing symptoms of trauma-related distress have been evaluated. In an article published in BMC Medicine, Tol and colleagues integrate their findings of the efficacy of universal school-based intervention across four countries and do not recommend classroom-based intervention as a treatment of trauma-related symptoms, since no consistent positive effects were found. On the contrary, for some children this type of universal intervention may impair recovery. Since universal school-based programs similar to the one evaluated here are widely implemented, Tol et al.'s results are highly relevant to inform the field of mental health service provision in war-affected countries.}, } @article {pmid24880932, year = {2014}, author = {Mishra, D and Mukhopadhyay, S and Chaturvedi, A and Kumari, S and Khan, MK}, title = {Cryptanalysis and improvement of Yan et al.'s biometric-based authentication scheme for telecare medicine information systems.}, journal = {Journal of medical systems}, volume = {38}, number = {6}, pages = {24}, pmid = {24880932}, issn = {1573-689X}, mesh = {Algorithms ; Biometric Identification/*instrumentation/standards ; Computer Security/*instrumentation/standards ; Health Information Exchange/*standards ; Telemedicine/*instrumentation/standards ; }, abstract = {Remote user authentication is desirable for a Telecare Medicine Information System (TMIS) for the safety, security and integrity of transmitted data over the public channel. In 2013, Tan presented a biometric based remote user authentication scheme and claimed that his scheme is secure. Recently, Yan et al. demonstrated some drawbacks in Tan's scheme and proposed an improved scheme to erase the drawbacks of Tan's scheme. We analyze Yan et al.'s scheme and identify that their scheme is vulnerable to off-line password guessing attack, and does not protect anonymity. Moreover, in their scheme, login and password change phases are inefficient to identify the correctness of input where inefficiency in password change phase can cause denial of service attack. Further, we design an improved scheme for TMIS with the aim to eliminate the drawbacks of Yan et al.'s scheme.}, } @article {pmid24838890, year = {2014}, author = {Kang, S and Kahan, S and Momeni, B}, title = {Simulating microbial community patterning using Biocellion.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {1151}, number = {}, pages = {233-253}, doi = {10.1007/978-1-4939-0554-6_16}, pmid = {24838890}, issn = {1940-6029}, mesh = {*Computer Simulation ; *Microbial Consortia ; Microbial Interactions ; *Models, Biological ; *Software ; Yeasts/*physiology ; }, abstract = {Mathematical modeling and computer simulation are important tools for understanding complex interactions between cells and their biotic and abiotic environment: similarities and differences between modeled and observed behavior provide the basis for hypothesis formation. Momeni et al. (Elife 2:e00230, 2013) investigated pattern formation in communities of yeast strains engaging in different types of ecological interactions, comparing the predictions of mathematical modeling, and simulation to actual patterns observed in wet-lab experiments. However, simulations of millions of cells in a three-dimensional community are extremely time consuming. One simulation run in MATLAB may take a week or longer, inhibiting exploration of the vast space of parameter combinations and assumptions. Improving the speed, scale, and accuracy of such simulations facilitates hypothesis formation and expedites discovery. Biocellion is a high-performance software framework for accelerating discrete agent-based simulation of biological systems with millions to trillions of cells. Simulations of comparable scale and accuracy to those taking a week of computer time using MATLAB require just hours using Biocellion on a multicore workstation. Biocellion further accelerates large scale, high resolution simulations using cluster computers by partitioning the work to run on multiple compute nodes. Biocellion targets computational biologists who have mathematical modeling backgrounds and basic C++ programming skills. This chapter describes the necessary steps to adapt the original Momeni et al.'s model to the Biocellion framework as a case study.}, } @article {pmid24829316, year = {2015}, author = {Topp, SM and Chipukuma, JM and Hanefeld, J}, title = {Understanding the dynamic interactions driving Zambian health centre performance: a case-based health systems analysis.}, journal = {Health policy and planning}, volume = {30}, number = {4}, pages = {485-499}, pmid = {24829316}, issn = {1460-2237}, mesh = {Computer Systems ; Delivery of Health Care/*organization & administration ; Developing Countries ; Government Programs/organization & administration ; Health Personnel/*organization & administration ; Health Resources/economics ; Humans ; Interviews as Topic ; Organizational Case Studies ; Primary Health Care/*organization & administration ; Social Responsibility ; Software ; Systems Analysis ; Zambia ; }, abstract = {BACKGROUND: Despite being central to achieving improved population health outcomes, primary health centres in low- and middle-income settings continue to underperform. Little research exists to adequately explain how and why this is the case. This study aimed to test the relevance and usefulness of an adapted conceptual framework for improving our understanding of the mechanisms and causal pathways influencing primary health centre performance.

METHODS: A theory-driven, case-study approach was adopted. Four Zambian health centres were purposefully selected with case data including health-care worker interviews (n = 60); patient interviews (n = 180); direct observation of facility operations (2 weeks/centre) and key informant interviews (n = 14). Data were analysed to understand how the performance of each site was influenced by the dynamic interactions between system 'hardware' and 'software' acting on mechanisms of accountability.

FINDINGS: Structural constraints including limited resources created challenging service environments in which work overload and stockouts were common. Health workers' frustration with such conditions interacted with dissatisfaction with salary levels eroding service values and acting as a catalyst for different forms of absenteeism. Such behaviours exacerbated patient-provider ratios and increased the frequency of clinical and administrative shortcuts. Weak health information systems and lack of performance data undermined providers' answerability to their employer and clients, and a lack of effective sanctions undermined supervisors' ability to hold providers accountable for these transgressions. Weak answerability and enforceability contributed to a culture of impunity that masked and condoned weak service performance in all four sites.

CONCLUSIONS: Health centre performance is influenced by mechanisms of accountability, which are in turn shaped by dynamic interactions between system hardware and system software. Our findings confirm the usefulness of combining Sheikh et al.'s (2011) hardware-software model with Brinkerhoff's (2004) typology of accountability to better understand how and why health centre micro-systems perform (or under-perform) under certain conditions.}, } @article {pmid24807035, year = {2014}, author = {Guo, D and Zhang, Y}, title = {Zhang neural network for online solution of time-varying linear matrix inequality aided with an equality conversion.}, journal = {IEEE transactions on neural networks and learning systems}, volume = {25}, number = {2}, pages = {370-382}, doi = {10.1109/TNNLS.2013.2275011}, pmid = {24807035}, issn = {2162-2388}, mesh = {Computer Simulation ; Humans ; *Linear Models ; *Models, Neurological ; *Neural Networks, Computer ; Neurons ; *Online Systems ; }, abstract = {In this paper, for online solution of time-varying linear matrix inequality (LMI), such an LMI is first converted to a time-varying matrix equation by introducing a time-varying matrix, of which each element is greater than or equal to zero. Then, by employing Zhang et al.'s neural dynamic method, a special recurrent neural network termed Zhang neural network (ZNN) is proposed and investigated for solving online the converted time-varying matrix equation as well as the time-varying LMI. Such a ZNN model showed in an explicit dynamics exploits the time-derivative information of time-varying coefficients. In addition, theoretical analysis and results of the proposed ZNN model are discussed and presented to show its excellent performance on solving the time-varying LMI. Computer simulation results further demonstrate the efficacy of the proposed ZNN model for online solution of the time-varying LMI and the converted time-varying matrix equation.}, } @article {pmid24803370, year = {2014}, author = {Denmark, T and Atkinson, J and Campbell, R and Swettenham, J}, title = {How do typically developing deaf children and deaf children with autism spectrum disorder use the face when comprehending emotional facial expressions in British sign language?.}, journal = {Journal of autism and developmental disorders}, volume = {44}, number = {10}, pages = {2584-2592}, pmid = {24803370}, issn = {1573-3432}, mesh = {Adolescent ; Child ; Child Development Disorders, Pervasive/diagnosis/epidemiology/*psychology ; Child, Preschool ; *Communication ; *Comprehension ; Deafness/diagnosis/epidemiology/*psychology ; Emotions ; *Facial Expression ; Female ; Humans ; Male ; *Sign Language ; }, abstract = {Facial expressions in sign language carry a variety of communicative features. While emotion can modulate a spoken utterance through changes in intonation, duration and intensity, in sign language specific facial expressions presented concurrently with a manual sign perform this function. When deaf adult signers cannot see facial features, their ability to judge emotion in a signed utterance is impaired (Reilly et al. in Sign Lang Stud 75:113-118, 1992). We examined the role of the face in the comprehension of emotion in sign language in a group of typically developing (TD) deaf children and in a group of deaf children with autism spectrum disorder (ASD). We replicated Reilly et al.'s (Sign Lang Stud 75:113-118, 1992) adult results in the TD deaf signing children, confirming the importance of the face in understanding emotion in sign language. The ASD group performed more poorly on the emotion recognition task than the TD children. The deaf children with ASD showed a deficit in emotion recognition during sign language processing analogous to the deficit in vocal emotion recognition that has been observed in hearing children with ASD.}, } @article {pmid24798241, year = {2014}, author = {Ma, Y and Zhang, H and Rahman, ZU and Wang, W and Li, X and Chen, H and Chen, X}, title = {Sensitive enantioanalysis of β-blockers via field-amplified sample injection combined with water removal in microemulsion electrokinetic chromatography.}, journal = {Electrophoresis}, volume = {35}, number = {19}, pages = {2772-2777}, doi = {10.1002/elps.201400008}, pmid = {24798241}, issn = {1522-2683}, mesh = {Adrenergic beta-Antagonists/*analysis/chemistry/*isolation & purification ; Chromatography, Micellar Electrokinetic Capillary/*methods ; Limit of Detection ; Linear Models ; Reproducibility of Results ; Stereoisomerism ; Water/chemistry ; }, abstract = {In this study, an on-line sample preconcentration technique, field-amplified sample injection combined with water removal by electroosmotic flow (EOF) pump, was applied to realize a highly sensitive chiral analysis of β-blocker enantiomers by MEEKC. The introduction of a water plug in capillary before the electrokinetic injection provided the effective preconcentration of chiral compounds. And then the water was moving out of the column from the injection end under the effect of the EOF, which avoided dilution of the stacked β-blocker enantiomers concentration suffering from the presence of water in separation buffer. Moreover, the addition of H3 PO4 and methanol in the sample solution greatly improved the enhancement efficiency further. Under optimized conditions, more than 2700-fold enhancement in sensitivity was obtained for each enantiomer of bupranolol (BU), alprenolol (AL), and propranolol (PRO) via electrokinetic injection. LODs were 0.10, 0.10, 0.12, 0.11, 0.02, and 0.02 ng/mL for S-BU, R-BU, S-AL, R-AL, S-PRO, and R-PRO, respectively. Eventually, the proposed method was successfully applied to the determination of BU, AL, and PRO in serum samples with good recoveries ranging from 93.4 to 98.2%.}, } @article {pmid24793832, year = {2014}, author = {Woolgar, A and Golland, P and Bode, S}, title = {Coping with confounds in multivoxel pattern analysis: what should we do about reaction time differences? A comment on Todd, Nystrom & Cohen 2013.}, journal = {NeuroImage}, volume = {98}, number = {}, pages = {506-512}, pmid = {24793832}, issn = {1095-9572}, support = {P41-EB015902/EB/NIBIB NIH HHS/United States ; U54 EB005149/EB/NIBIB NIH HHS/United States ; U54-EB005149/EB/NIBIB NIH HHS/United States ; P41 RR013218/RR/NCRR NIH HHS/United States ; P41 EB015902/EB/NIBIB NIH HHS/United States ; }, mesh = {Brain/*physiology ; Brain Mapping/*methods ; Humans ; Magnetic Resonance Imaging/*methods ; Multivariate Analysis ; *Reaction Time ; Sensitivity and Specificity ; Statistics as Topic ; }, abstract = {Multivoxel pattern analysis (MVPA) is a sensitive and increasingly popular method for examining differences between neural activation patterns that cannot be detected using classical mass-univariate analysis. Recently, Todd et al. ("Confounds in multivariate pattern analysis: Theory and rule representation case study", 2013, NeuroImage 77: 157-165) highlighted a potential problem for these methods: high sensitivity to confounds at the level of individual participants due to the use of directionless summary statistics. Unlike traditional mass-univariate analyses where confounding activation differences in opposite directions tend to approximately average out at group level, group level MVPA results may be driven by any activation differences that can be discriminated in individual participants. In Todd et al.'s empirical data, factoring out differences in reaction time (RT) reduced a classifier's ability to distinguish patterns of activation pertaining to two task rules. This raises two significant questions for the field: to what extent have previous multivoxel discriminations in the literature been driven by RT differences, and by what methods should future studies take RT and other confounds into account? We build on the work of Todd et al. and compare two different approaches to remove the effect of RT in MVPA. We show that in our empirical data, in contrast to that of Todd et al., the effect of RT on rule decoding is negligible, and results were not affected by the specific details of RT modelling. We discuss the meaning of and sensitivity for confounds in traditional and multivoxel approaches to fMRI analysis. We observe that the increased sensitivity of MVPA comes at a price of reduced specificity, meaning that these methods in particular call for careful consideration of what differs between our conditions of interest. We conclude that the additional complexity of the experimental design, analysis and interpretation needed for MVPA is still not a reason to favour a less sensitive approach.}, } @article {pmid24781814, year = {2014}, author = {Wen, F and Guo, D}, title = {An improved anonymous authentication scheme for telecare medical information systems.}, journal = {Journal of medical systems}, volume = {38}, number = {5}, pages = {26}, pmid = {24781814}, issn = {1573-689X}, mesh = {*Computer Security ; *Confidentiality ; Electronic Health Records/*organization & administration ; Humans ; Patient Identification Systems/*organization & administration ; Telemedicine/*organization & administration ; *User-Computer Interface ; }, abstract = {Telecare medical information system (TMIS) constructs an efficient and convenient connection between patients and the medical server. The patients can enjoy medical services through public networks, and hence the protection of patients' privacy is very significant. Very recently, Wu et al. identified Jiang et al.'s authentication scheme had some security drawbacks and proposed an enhanced authentication scheme for TMIS. However, we analyze Wu et al.'s scheme and show that their scheme suffers from server spoofing attack, off-line password guessing attack, impersonation attack. Moreover, Wu et al.'s scheme fails to preserve the claimed patient anonymity and its password change phase is unfriendly and inefficient. Thereby, we present a novel anonymous authentication scheme for telecare medical information systems to eliminate the aforementioned faults. Besides, We demonstrate the completeness of the proposed scheme through the BAN logic. Furthermore, the security of our proposed scheme is proven through Bellare and Rogaways model. Compared with the related existing schemes, our scheme is more secure.}, } @article {pmid24778202, year = {2014}, author = {Waitman, LR and Aaronson, LS and Nadkarni, PM and Connolly, DW and Campbell, JR}, title = {The Greater Plains Collaborative: a PCORnet Clinical Research Data Network.}, journal = {Journal of the American Medical Informatics Association : JAMIA}, volume = {21}, number = {4}, pages = {637-641}, pmid = {24778202}, issn = {1527-974X}, support = {UL1 TR000001/TR/NCATS NIH HHS/United States ; UL1TR000001/TR/NCATS NIH HHS/United States ; }, mesh = {*Computer Communication Networks ; Electronic Health Records/*organization & administration ; Humans ; *Information Dissemination ; Midwestern United States ; Outcome Assessment, Health Care/*organization & administration ; *Patient-Centered Care ; }, abstract = {The Greater Plains Collaborative (GPC) is composed of 10 leading medical centers repurposing the research programs and informatics infrastructures developed through Clinical and Translational Science Award initiatives. Partners are the University of Kansas Medical Center, Children's Mercy Hospital, University of Iowa Healthcare, the University of Wisconsin-Madison, the Medical College of Wisconsin and Marshfield Clinic, the University of Minnesota Academic Health Center, the University of Nebraska Medical Center, the University of Texas Health Sciences Center at San Antonio, and the University of Texas Southwestern Medical Center. The GPC network brings together a diverse population of 10 million people across 1300 miles covering seven states with a combined area of 679 159 square miles. Using input from community members, breast cancer was selected as a focus for cohort building activities. In addition to a high-prevalence disorder, we also selected a rare disease, amyotrophic lateral sclerosis.}, } @article {pmid24775156, year = {2014}, author = {Gallese, V and Sinigaglia, C}, title = {Understanding action with the motor system.}, journal = {The Behavioral and brain sciences}, volume = {37}, number = {2}, pages = {199-200}, doi = {10.1017/S0140525X13002288}, pmid = {24775156}, issn = {1469-1825}, mesh = {Animals ; *Biological Evolution ; Brain/*physiology ; Humans ; Learning/*physiology ; Mirror Neurons/*physiology ; *Social Perception ; }, abstract = {We challenge Cook et al.'s claim about the vagueness of the notion of action understanding in relation with mirror neurons. We show the multidimensional nature of action understanding and provide a definition of motor-based action understanding, shedding new light on the various components of action understanding and on their relationship. Finally, we propose an alternative perspective on the origin of mirror neurons, stressing the necessity to abandon the dichotomy between genetic and associative hypotheses.}, } @article {pmid24775148, year = {2014}, author = {Behme, C}, title = {The role of mirror neurons in language acquisition and evolution.}, journal = {The Behavioral and brain sciences}, volume = {37}, number = {2}, pages = {192-193}, doi = {10.1017/S0140525X13002203}, pmid = {24775148}, issn = {1469-1825}, mesh = {Animals ; *Biological Evolution ; Brain/*physiology ; Humans ; Learning/*physiology ; Mirror Neurons/*physiology ; *Social Perception ; }, abstract = {I argue that Cook et al.'s attack of the genetic hypothesis of mirror neurons misses its target because the authors miss the point that genetics may specify how neurons may learn, not what they learn. Paying more attention to recent work linking mirror neurons to language acquisition and evolution would strengthen Cook et al.'s arguments against a rigid genetic hypothesis.}, } @article {pmid24773506, year = {2014}, author = {Dalenberg, CJ and Brand, BL and Loewenstein, RJ and Gleaves, DH and Dorahy, MJ and Cardeña, E and Frewen, PA and Carlson, EB and Spiegel, D}, title = {Reality versus fantasy: reply to Lynn et al. (2014).}, journal = {Psychological bulletin}, volume = {140}, number = {3}, pages = {911-920}, doi = {10.1037/a0036685}, pmid = {24773506}, issn = {1939-1455}, mesh = {Amnesia/*etiology ; Child Abuse/*psychology ; Dissociative Disorders/*etiology ; *Fantasy ; Humans ; *Models, Psychological ; Stress Disorders, Post-Traumatic/*complications ; }, abstract = {We respond to Lynn et al.'s (2014) comments on our review (Dalenberg et al., 2012) demonstrating the superiority of the trauma model (TM) over the fantasy model (FM) in explaining the trauma-dissociation relationship. Lynn et al. conceded that our meta-analytic results support the TM hypothesis that trauma exposure is a causal risk factor for the development of dissociation. Although Lynn et al. suggested that our meta-analyses were selective, we respond that each omitted study failed to meet inclusion criteria; our meta-analyses thus reflect a balanced view of the predominant trauma-dissociation findings. In contrast, Lynn et al. were hypercritical of studies that supported the TM while ignoring methodological problems in studies presented as supportive of the FM. We clarify Lynn et al.'s misunderstandings of the TM and demonstrate consistent superiority in prediction of time course of dissociative symptoms, response to psychotherapy of dissociative patients, and pattern of relationships of trauma to dissociation. We defend our decision not to include studies using the Dissociative Experiences Scale-Comparison, a rarely used revision of the Dissociative Experiences Scale that shares less than 10% of the variance with the original scale. We highlight several areas of agreement: (a) Trauma plays a complex role in dissociation, involving indirect and direct paths; (b) dissociation-suggestibility relationships are small; and (c) controls and measurement issues should be addressed in future suggestibility and dissociation research. Considering the lack of evidence that dissociative individuals simply fantasize trauma, future researchers should examine more complex models of trauma and valid measures of dissociation.}, } @article {pmid24773505, year = {2014}, author = {Lynn, SJ and Lilienfeld, SO and Merckelbach, H and Giesbrecht, T and McNally, RJ and Loftus, EF and Bruck, M and Garry, M and Malaktaris, A}, title = {The trauma model of dissociation: inconvenient truths and stubborn fictions. Comment on Dalenberg et al. (2012).}, journal = {Psychological bulletin}, volume = {140}, number = {3}, pages = {896-910}, doi = {10.1037/a0035570}, pmid = {24773505}, issn = {1939-1455}, mesh = {Amnesia/*etiology ; Child Abuse/*psychology ; Dissociative Disorders/*etiology ; *Fantasy ; Humans ; *Models, Psychological ; Stress Disorders, Post-Traumatic/*complications ; }, abstract = {Dalenberg et al. (2012) argued that convincing evidence (a) supports the longstanding trauma model (TM), which posits that early trauma plays a key role in the genesis of dissociation; and (b) refutes the fantasy model (FM), which posits that fantasy proneness, suggestibility, cognitive failures, and other variables foster dissociation. We review evidence bearing on Dalenberg et al.'s 8 predictions and find them largely wanting in empirical support. We contend that the authors repeat errors committed by many previous proponents of the TM, such as attributing a central etiological role to trauma in the absence of sufficient evidence. Specifically, Dalenberg et al. leap too quickly from correlational data to causal conclusions, do not adequately consider the lack of corroboration of abuse in many studies, and underestimate the relation between dissociation and false memories. Nevertheless, we identify points of agreement between the TM and FM regarding potential moderators and mediators of dissociative symptoms (e.g., family environment, biological vulnerabilities) and the hypothesis that dissociative identity disorder is a disorder of self-understanding. We acknowledge that trauma may play a causal role in dissociation but that this role is less central and specific than Dalenberg et al. contend. Finally, although a key assumption of the TM is dissociative amnesia, the notion that people can encode traumatic experiences without being able to recall them lacks strong empirical support. Accordingly, we conclude that the field should now abandon the simple trauma-dissociation model and embrace multifactorial models that accommodate the diversity of causes of dissociation and dissociative disorders.}, } @article {pmid24763573, year = {2014}, author = {Zollikofer, CP and Ponce de León, MS and Margvelashvili, A and Rightmire, GP and Lordkipanidze, D}, title = {Response to comment on "A complete skull from Dmanisi, Georgia, and the evolutionary biology of early Homo".}, journal = {Science (New York, N.Y.)}, volume = {344}, number = {6182}, pages = {360}, doi = {10.1126/science.1250081}, pmid = {24763573}, issn = {1095-9203}, mesh = {Animals ; *Biological Evolution ; Face/*anatomy & histology ; *Fossils ; Hominidae/*anatomy & histology ; Humans ; Skull/*anatomy & histology ; }, abstract = {Schwartz et al. hold that variation among the Dmanisi skulls reflects taxic diversity. The morphological observations to support their hypothesis, however, are partly incorrect, and not calibrated against intraspecific variation in living taxa. After proper adjustment, Schwartz et al.'s data are fully compatible with the hypothesis of a single paleodeme of early Homo at Dmanisi.}, } @article {pmid24762459, year = {2014}, author = {Kogure, T and Sumitani, M and Suka, M and Ishikawa, H and Odajima, T and Igarashi, A and Kusama, M and Okamoto, M and Sugimori, H and Kawahara, K}, title = {Validity and reliability of the Japanese version of the Newest Vital Sign: a preliminary study.}, journal = {PloS one}, volume = {9}, number = {4}, pages = {e94582}, pmid = {24762459}, issn = {1932-6203}, mesh = {Aged ; Analgesics, Opioid/therapeutic use ; Chronic Pain/drug therapy ; Female ; *Health Literacy ; Humans ; Japan ; Likelihood Functions ; Male ; Middle Aged ; Needs Assessment ; Quality of Life ; ROC Curve ; Reproducibility of Results ; Surveys and Questionnaires ; Translating ; }, abstract = {Health literacy (HL) refers to the ability to obtain, process, and understand basic health information and services, and is thus needed to make appropriate health decisions. The Newest Vital Sign (NVS) is comprised of 6 questions about an ice cream nutrition label and assesses HL numeracy skills. We developed a Japanese version of the NVS (NVS-J) and evaluated the validity and reliability of the NVS-J in patients with chronic pain. The translation of the original NVS into Japanese was achieved as per the published guidelines. An observational study was subsequently performed to evaluate the validity and reliability of the NVS-J in 43 Japanese patients suffering from chronic pain. Factor analysis with promax rotation, using the Kaiser criterion (eigenvalues ≥1.0), and a scree plot revealed that the main component of the NVS-J consists of three determinative factors, and each factor consists of two NVS-J items. The criterion-related validity of the total NVS-J score was significantly correlated with the total score of Ishikawa et al.'s self-rated HL Questionnaire, the clinical global assessment of comprehensive HL level, cognitive function, and the Brinkman index. In addition, Cronbach's coefficient for the total score of the NVS-J was adequate (alpha = 0.72). This study demonstrated that the NVS-J has good validity and reliability. Further, the NVS-J consists of three determinative factors: "basic numeracy ability," "complex numeracy ability," and "serious-minded ability." These three HL abilities comprise a 3-step hierarchical structure. Adequate HL should be promoted in chronic pain patients to enable coping, improve functioning, and increase activities of daily living (ADLs) and quality of life (QOL).}, } @article {pmid24760224, year = {2014}, author = {Wen, F}, title = {A more secure anonymous user authentication scheme for the integrated EPR information system.}, journal = {Journal of medical systems}, volume = {38}, number = {5}, pages = {42}, pmid = {24760224}, issn = {1573-689X}, mesh = {*Computer Communication Networks ; *Computer Security ; Confidentiality ; Delivery of Health Care, Integrated/*organization & administration ; Electronic Health Records/*organization & administration ; Humans ; Patient Identification Systems/*organization & administration ; Telemedicine/*organization & administration ; *User-Computer Interface ; }, abstract = {Secure and efficient user mutual authentication is an essential task for integrated electronic patient record (EPR) information system. Recently, several authentication schemes have been proposed to meet this requirement. In a recent paper, Lee et al. proposed an efficient and secure password-based authentication scheme used smart cards for the integrated EPR information system. This scheme is believed to have many abilities to resist a range of network attacks. Especially, they claimed that their scheme could resist lost smart card attack. However, we reanalyze the security of Lee et al.'s scheme, and show that it fails to protect off-line password guessing attack if the secret information stored in the smart card is compromised. This also renders that their scheme is insecure against user impersonation attacks. Then, we propose a new user authentication scheme for integrated EPR information systems based on the quadratic residues. The new scheme not only resists a range of network attacks but also provides user anonymity. We show that our proposed scheme can provide stronger security.}, } @article {pmid24755843, year = {2014}, author = {Guo, Q and Parlar, M and Truong, W and Hall, G and Thabane, L and McKinnon, M and Goeree, R and Pullenayegum, E}, title = {The reporting of observational clinical functional magnetic resonance imaging studies: a systematic review.}, journal = {PloS one}, volume = {9}, number = {4}, pages = {e94412}, pmid = {24755843}, issn = {1932-6203}, mesh = {Humans ; *Magnetic Resonance Imaging ; Publications/statistics & numerical data ; *Research Report ; Software ; Time Factors ; }, abstract = {INTRODUCTION: Complete reporting assists readers in confirming the methodological rigor and validity of findings and allows replication. The reporting quality of observational functional magnetic resonance imaging (fMRI) studies involving clinical participants is unclear.

OBJECTIVES: We sought to determine the quality of reporting in observational fMRI studies involving clinical participants.

METHODS: We searched OVID MEDLINE for fMRI studies in six leading journals between January 2010 and December 2011.Three independent reviewers abstracted data from articles using an 83-item checklist adapted from the guidelines proposed by Poldrack et al. (Neuroimage 2008; 40: 409-14). We calculated the percentage of articles reporting each item of the checklist and the percentage of reported items per article.

RESULTS: A random sample of 100 eligible articles was included in the study. Thirty-one items were reported by fewer than 50% of the articles and 13 items were reported by fewer than 20% of the articles. The median percentage of reported items per article was 51% (ranging from 30% to 78%). Although most articles reported statistical methods for within-subject modeling (92%) and for between-subject group modeling (97%), none of the articles reported observed effect sizes for any negative finding (0%). Few articles reported justifications for fixed-effect inferences used for group modeling (3%) and temporal autocorrelations used to account for within-subject variances and correlations (18%). Other under-reported areas included whether and how the task design was optimized for efficiency (22%) and distributions of inter-trial intervals (23%).

CONCLUSIONS: This study indicates that substantial improvement in the reporting of observational clinical fMRI studies is required. Poldrack et al.'s guidelines provide a means of improving overall reporting quality. Nonetheless, these guidelines are lengthy and may be at odds with strict word limits for publication; creation of a shortened-version of Poldrack's checklist that contains the most relevant items may be useful in this regard.}, } @article {pmid24740999, year = {2016}, author = {Marasini, D and Quatto, P and Ripamonti, E}, title = {Assessing the inter-rater agreement for ordinal data through weighted indexes.}, journal = {Statistical methods in medical research}, volume = {25}, number = {6}, pages = {2611-2633}, doi = {10.1177/0962280214529560}, pmid = {24740999}, issn = {1477-0334}, mesh = {Carcinoma in Situ/classification/diagnosis/pathology ; Female ; Humans ; Monte Carlo Method ; *Observer Variation ; Reproducibility of Results ; Uterine Cervical Neoplasms/classification/diagnosis/pathology ; }, abstract = {Assessing the inter-rater agreement between observers, in the case of ordinal variables, is an important issue in both the statistical theory and biomedical applications. Typically, this problem has been dealt with the use of Cohen's weighted kappa, which is a modification of the original kappa statistic, proposed for nominal variables in the case of two observers. Fleiss (1971) put forth a generalization of kappa in the case of multiple observers, but both Cohen's and Fleiss' kappa could have a paradoxical behavior, which may lead to a difficult interpretation of their magnitude. In this paper, a modification of Fleiss' kappa, not affected by paradoxes, is proposed, and subsequently generalized to the case of ordinal variables. Monte Carlo simulations are used both to testing statistical hypotheses and to calculating percentile and bootstrap-t confidence intervals based on this statistic. The normal asymptotic distribution of the proposed statistic is demonstrated. Our results are applied to the classical Holmquist et al.'s (1967) dataset on the classification, by multiple observers, of carcinoma in situ of the uterine cervix. Finally, we generalize the use of s* to a bivariate case.}, } @article {pmid24726398, year = {2014}, author = {Sarlo, M and Lotto, L and Rumiati, R and Palomba, D}, title = {If it makes you feel bad, don't do it! Egoistic rather than altruistic empathy modulates neural and behavioral responses in moral dilemmas.}, journal = {Physiology & behavior}, volume = {130}, number = {}, pages = {127-134}, doi = {10.1016/j.physbeh.2014.04.002}, pmid = {24726398}, issn = {1873-507X}, mesh = {Arousal ; Brain/*physiology ; Cognition/physiology ; Decision Making/*physiology ; Electroencephalography ; Emotions/*physiology ; Empathy/*physiology ; Evoked Potentials ; Female ; Humans ; Male ; *Morals ; Psychological Tests ; Regression Analysis ; *Self Concept ; Young Adult ; }, abstract = {According to Greene et al.'s dual-process theory, the differential involvement of emotional processes would explain the different patterns of moral judgments people typically produce when faced with Trolley- and Footbridge-type dilemmas. As a relevant factor, dispositional empathy is known to motivate prosocial behaviors, thus playing a central role in moral judgment and behavior. The present study was aimed at investigating how behavioral and neural correlates of moral decision-making are modulated by the cognitive and affective dimensions of empathy. Thirty-seven participants were presented with 30 Footbridge-type and 30 Trolley-type dilemmas. Participants were required to decide between two options: letting some people die (non-utilitarian) vs. killing one person to save more people (utilitarian). Event-related potentials (ERPs) were recorded stimulus-locked to a "decision slide". Response choices and ratings of valence and arousal were also collected. Trait empathy was measured through the Interpersonal Reactivity Index (IRI), assessing both the cognitive and affective dimensions. Scores on the Empathic Concern affective subscale of the IRI positively predicted unpleasantness experienced during decision-making for all dilemmas. On the other hand, for Footbridge-type dilemmas only, scores on the Personal Distress affective subscale predicted negatively the mean percentages of utilitarian choices and positively the mean amplitudes of the P260, an ERP component reflecting an immediate emotional reaction during decision-making. It is concluded that "self-oriented" feelings of anxiety and unease, rather than "other-oriented" feelings of concern, affect behavioral choices and emotion-related cortical activity in Footbridge-type moral dilemmas.}, } @article {pmid24713362, year = {2014}, author = {Bennett, LW}, title = {Comments on Stuart et al.'s "Genetic associations with intimate partner violence in a sample of hazardous drinking men in batterer intervention programs".}, journal = {Violence against women}, volume = {20}, number = {4}, pages = {406-413}, doi = {10.1177/1077801214528584}, pmid = {24713362}, issn = {1552-8448}, mesh = {*Aggression ; Female ; Humans ; Male ; *Polymorphism, Genetic ; *Spouse Abuse ; Substance-Related Disorders/*complications ; }, abstract = {Stuart et al. correlate genetic characteristics of men in batterer intervention programs with their level of intimate partner violence (IPV). In this commentary, I address the generality of the results in light of the characteristics of the participants, speculate about possible effects of current and future genetic and biological research on potential consumers of such research, and place this research in the context on an ongoing criticism of batterer intervention programs by various constituents.}, } @article {pmid24708199, year = {2014}, author = {Zhang, R and Hu, Z and Li, B and Yang, J}, title = {Efficient method for fast simulation of scanning tunneling microscopy with a tip effect.}, journal = {The journal of physical chemistry. A}, volume = {118}, number = {39}, pages = {8953-8959}, doi = {10.1021/jp5018218}, pmid = {24708199}, issn = {1520-5215}, abstract = {On the basis of Bardeen's perturbation theory on electron tunneling and inspired by Paz et al.'s study, a new expression for the tunneling current between the scanning tunneling microscopy (STM) tip and sample has been obtained, and it provides us with an efficient method to simulate STM images. The method can be implemented in any code of first-principles computing software, which offers the wave functions of the tip and sample, calculated independently at the same footing, as input. By calculating the integral with fast Fourier transform (FFT), simulating the STM image of a given sample surface by a database of different tips on a PC turns out to be not a time-consuming work. Compared with Paz et al.'s method, our method abandons the application of the vacuum Green function and possesses better computing efficiency, fewer parameters, and more reasonable simulated results especially at lower computing cost. Simple tip-sample systems, such as H-H and Pd2-Ag2, are taken as benchmarks to test our method. The topographic images of a CO molecule adsorbed on a Cu(111) surface obtained by using a tungsten tip and a CO-terminated tip are also simulated, and the simulated results are in good agreement with the experimental ones.}, } @article {pmid24697213, year = {2014}, author = {Rallapalli, SK and Namjoshi, OA and Tiruveedhula, VV and Deschamps, JR and Cook, JM}, title = {Stereospecific total synthesis of the indole alkaloid ervincidine. Establishment of the C-6 hydroxyl stereochemistry.}, journal = {The Journal of organic chemistry}, volume = {79}, number = {9}, pages = {3776-3780}, pmid = {24697213}, issn = {1520-6904}, support = {R01 NS076517/NS/NINDS NIH HHS/United States ; Y1-DA1101/DA/NIDA NIH HHS/United States ; R01 MH096463/MH/NIMH NIH HHS/United States ; R01 MH046851/MH/NIMH NIH HHS/United States ; R01 HL118561/HL/NHLBI NIH HHS/United States ; }, mesh = {Indole Alkaloids/*chemical synthesis/chemistry ; Models, Molecular ; Molecular Conformation ; Stereoisomerism ; }, abstract = {The total synthesis of the indole alkaloid ervincidine (3) is reported. This research provides a general entry into C-6 hydroxy-substituted indole alkaloids with either an α or a β configuration. This study corrects the errors in Glasby's book (Glasby, J. S. Encyclopedia of the Alkaloids; Plenum Press: New York, 1975) and Lounasmaa et al.'s review (Lounasmaa, M.; Hanhinen, P.; Westersund, M. In The Alkaloids; Cordell, G. A., Ed.; Academic Press: San Diego, CA, 1999; Vol. 52, pp 103-195) as well as clarifies the work of Yunusov et al. (Malikov, V. M.; Sharipov, M. R.; Yunusov, S. Yu. Khim. Prir. Soedin. 1972, 8, 760-761. Rakhimov, D. A.; Sharipov, M. R.; Aripov, Kh. N.; Malikov, V. M.; Shakirov, T. T.; Yunusov, S. Yu. Khim. Prir. Soedin. 1970, 6, 724-725). It establishes the correct absolute configuration of the C-6 hydroxyl function in ervincidine. This serves as a structure proof and corrects the misassigned structure reported in the literature.}, } @article {pmid24680786, year = {2014}, author = {Rasker, JJ and Wolfe, F}, title = {McLean et al.’s paper, ‘‘Incidence and predictors of neck and widespread pain after motor vehicle collision among U.S. litigants and nonlitigants’’.}, journal = {Pain}, volume = {155}, number = {7}, pages = {1416}, doi = {10.1016/j.pain.2014.03.016}, pmid = {24680786}, issn = {1872-6623}, mesh = {Accidents, Traffic/*legislation & jurisprudence ; Emergency Service, Hospital/*legislation & jurisprudence ; Female ; Humans ; Male ; Neck Pain/*diagnosis/*epidemiology ; Whiplash Injuries/*diagnosis/*epidemiology ; }, } @article {pmid24675286, year = {2014}, author = {Conklin, HM and Reddick, WE and Khan, RB}, title = {Comment on Smithson et al.'s review of stimulant medication usage to improve neurocognitive and learning outcomes in childhood brain tumour survivors.}, journal = {European journal of cancer (Oxford, England : 1990)}, volume = {50}, number = {8}, pages = {1566-1568}, doi = {10.1016/j.ejca.2014.01.032}, pmid = {24675286}, issn = {1879-0852}, mesh = {Brain Neoplasms/*physiopathology ; Central Nervous System Stimulants/*therapeutic use ; Cognition/*drug effects ; Female ; Humans ; Learning/*drug effects ; Male ; Methylphenidate/*therapeutic use ; }, } @article {pmid24672220, year = {2014}, author = {Liu, J and Zhang, HX}, title = {Polymorphism in the 11q24.1 genomic region is associated with myopia: a comprehensive genetic study in Chinese and Japanese populations.}, journal = {Molecular vision}, volume = {20}, number = {}, pages = {352-358}, pmid = {24672220}, issn = {1090-0535}, mesh = {Asian People/*genetics ; China ; Chromosomes, Human, Pair 11/*genetics ; Female ; Genetic Association Studies ; Genetic Heterogeneity ; *Genetic Predisposition to Disease ; Genome, Human/*genetics ; Humans ; Japan ; Male ; Myopia/*genetics ; Polymorphism, Single Nucleotide/*genetics ; Publication Bias ; }, abstract = {PURPOSE: To evaluate the association of polymorphisms in the 11q24.1 genomic region and the CTNND2 gene with myopia.

METHODS: We conducted a comprehensive meta-analysis included 6,954 cases and 9,346 controls. Odds ratios (ORs) were calculated using Carlin's method. Publication bias was assessed using Egger et al.'s approach. Sensitivity, heterogeneity, and trim and fill analyses were also conducted.

RESULTS: For the 11q24.1 genomic region, the rs11218544 polymorphism showed significant association with myopia [OR and 95% confidence interval (CI): 1.167 (1.032-1.319), p=0.013], while rs577948 showed no association with the disease [OR and 95%CI: 0.988 (0.727-1.342), p=0.936]. For the CTNND2 gene, neither rs6885224 nor rs12716080 was significantly associated with myopia {rs6885224: [OR and 95%CI: 1.051 (0.795-1.391), p=0.725], rs12716080: [OR and 95%CI: 1.173 (0.990-1.390), p=0.065]} .

CONCLUSIONS: Our study indicated that the 11q24.1 genomic region, and particularly the rs11218544 polymorphism, has a genetic association with the development of myopia.}, } @article {pmid24667839, year = {2014}, author = {Heritage, B and Pollock, C and Roberts, L}, title = {Validation of the organizational culture assessment instrument.}, journal = {PloS one}, volume = {9}, number = {3}, pages = {e92879}, pmid = {24667839}, issn = {1932-6203}, mesh = {Adult ; Aged ; Cross-Sectional Studies ; Female ; Humans ; *Job Satisfaction ; Male ; *Psychology, Industrial ; }, abstract = {Organizational culture is a commonly studied area in industrial/organizational psychology due to its important role in workplace behaviour, cognitions, and outcomes. Jung et al.'s [1] review of the psychometric properties of organizational culture measurement instruments noted many instruments have limited validation data despite frequent use in both theoretical and applied situations. The Organizational Culture Assessment Instrument (OCAI) has had conflicting data regarding its psychometric properties, particularly regarding its factor structure. Our study examined the factor structure and criterion validity of the OCAI using robust analysis methods on data gathered from 328 (females = 226, males = 102) Australian employees. Confirmatory factor analysis supported a four factor structure of the OCAI for both ideal and current organizational culture perspectives. Current organizational culture data demonstrated expected reciprocally-opposed relationships between three of the four OCAI factors and the outcome variable of job satisfaction but ideal culture data did not, thus indicating possible weak criterion validity when the OCAI is used to assess ideal culture. Based on the mixed evidence regarding the measure's properties, further examination of the factor structure and broad validity of the measure is encouraged.}, } @article {pmid24661276, year = {2014}, author = {Beatty, AS and Barratt, CL and Berry, CM and Sackett, PR}, title = {Testing the generalizability of indirect range restriction corrections.}, journal = {The Journal of applied psychology}, volume = {99}, number = {4}, pages = {587-598}, doi = {10.1037/a0036361}, pmid = {24661276}, issn = {1939-1854}, mesh = {Adult ; Humans ; *Models, Statistical ; Personnel Selection/*statistics & numerical data ; }, abstract = {Range restriction is a common problem in personnel selection and other contexts in applied psychology. For many years researchers have used corrections that assume range restriction was direct, even when it was known that range restriction was indirect. Hunter, Schmidt, and Le (2006) proposed a new correction for cases of indirect range restriction that greatly increases its potential usefulness due to its reduced information requirements compared to alternatives. The current study examines the applicability of Hunter et al.'s correction to settings where its assumed structural model is violated by including the measures that are to be involved in corrections in the original selection composite. We conclude that Hunter et al.'s correction should generally be preferred when compared to its common alternative, Thorndike's Case II correction for direct range restriction. However, this is due to the likely violation of one of the other assumptions of the Hunter et al. correction in most applied settings. Correction mechanisms and practical implications are discussed.}, } @article {pmid24661177, year = {2014}, author = {Suchy, Y and Eastvold, AD and Strassberg, DS and Franchow, EI}, title = {Understanding processing speed weaknesses among pedophilic child molesters: response style vs. neuropathology.}, journal = {Journal of abnormal psychology}, volume = {123}, number = {1}, pages = {273-285}, doi = {10.1037/a0035812}, pmid = {24661177}, issn = {1939-1846}, mesh = {Adult ; Child ; Child Abuse, Sexual/*psychology ; Criminals/*psychology ; Executive Function/physiology ; Humans ; Male ; Memory, Short-Term/*physiology ; Neuropsychological Tests ; Pedophilia/*psychology ; Reaction Time/physiology ; Visual Perception/physiology ; Young Adult ; }, abstract = {Research shows that pedophilic (PED) child molesters exhibit slower performance speed and greater performance accuracy when compared to nonpedophilic (N-PED) child molesters or other criminal and noncriminal controls. The purpose of the present study was to examine whether these differences reflect a slow/deliberate response style among PEDS (as we have previously hypothesized; Eastvold, Suchy, & Strassberg, 2011; Suchy, Whittaker, Strassberg, & Eastvold, 2009a, 2009b), or a fundamental neuropathological weakness in processing speed. Data came from a larger study examining neurocognition among sex offenders. Processing speed in three different domains (motor speed, visual-perceptual speed, and visual-motor integration) was examined in 20 phallometrically identified PEDs, 20 N-PEDs, and 20 nonsexual offenders, using both clinical (Finger Tapping, Symbol Search, Digit Symbol Coding) and experimental measures (Inspection Time Task [ITT]). The ITT assessed speed of visual-perceptual processing independent of response speed. On clinical measures, PEDs exhibited slower visual perception [F(2, 57) = 5.24, p = .008] and visual-motor integration [F(2, 57) = 5.02, p = .010] than the other groups, with no differences for simple motor speed. On the ITT, PEDs performed less accurately than the other groups [F(2, 57) = 3.95, p = .025], clearly indicating that slow processing speed cannot be explained by a deliberate response style. Group differences persisted after controlling for other potential confounds (age, estimate IQ, working memory, ethnicity, and substance use). PEDs' slower performance is due to a fundamental neurocognitive weakness, rather than a slow/deliberate response style. These results are consistent with Cantor et al.'s (2008) work identifying white matter abnormalities among PEDs and provide further support for a neurodevelopmental etiology of pedophilia.}, } @article {pmid24660688, year = {2015}, author = {Kivlighan, DM and Gelso, CJ and Ain, S and Hummel, AM and Markin, RD}, title = {The therapist, the client, and the real relationship: an actor-partner interdependence analysis of treatment outcome.}, journal = {Journal of counseling psychology}, volume = {62}, number = {2}, pages = {314-320}, doi = {10.1037/cou0000012}, pmid = {24660688}, issn = {0022-0167}, mesh = {Female ; *Health Personnel ; Humans ; Male ; Models, Psychological ; Perception ; *Professional-Patient Relations ; Treatment Outcome ; }, abstract = {The relationship between treatment progress (as rated by both clients and therapists) and real relationship (also rated by both clients and therapists) was decomposed into between-therapist and within-therapist (between-client) effects and analyzed using the actor-partner interdependence model. We reanalyzed a subset of the data, 12 therapists and 32 clients, from Gelso et al.'s (2012) study of brief, theoretically diverse outpatient treatment. Consistent with and extending previous research, clients whose therapists provided higher average levels of client-perceived real relationship across the clients treated by a given therapist had better progress ratings from both themselves and their therapists. Within each therapist's caseload, differences between clients in client- or therapist-rated real relationship were unrelated to either client- or therapist-rated outcome. Clients whose therapists provided higher average levels of therapist-perceived real relationship, across the clients treated by the therapist, had worse progress ratings from the therapists. The results provide additional evidence for the importance of between-therapist differences in therapeutic relationship qualities, both client and therapist rated.}, } @article {pmid24656955, year = {2014}, author = {Farsalinos, KE and Voudris, V}, title = {E-cigarette use and indoor air quality: methodological limitations: response to W. Schober et al.'s "use of electronic cigarettes (e-cigarettes) impairs indoor air quality and increases FeNO levels of e-cigarette consumers".}, journal = {International journal of hygiene and environmental health}, volume = {217}, number = {6}, pages = {705-706}, doi = {10.1016/j.ijheh.2014.02.001}, pmid = {24656955}, issn = {1618-131X}, mesh = {Air Pollutants/*analysis ; Air Pollution, Indoor/*analysis ; Electronic Nicotine Delivery Systems/*adverse effects ; Humans ; Lung/*metabolism ; Male ; Nitric Oxide/*metabolism ; }, } @article {pmid24656180, year = {2014}, author = {Ingebrigtsen, T and Georgiou, A and Clay-Williams, R and Magrabi, F and Hordern, A and Prgomet, M and Li, J and Westbrook, J and Braithwaite, J}, title = {The impact of clinical leadership on health information technology adoption: systematic review.}, journal = {International journal of medical informatics}, volume = {83}, number = {6}, pages = {393-405}, doi = {10.1016/j.ijmedinf.2014.02.005}, pmid = {24656180}, issn = {1872-8243}, mesh = {Clinical Competence/*standards ; *Health Personnel ; Humans ; *Leadership ; Medical Informatics/*organization & administration/*standards ; *Physician's Role ; }, abstract = {PURPOSE: To conduct a systematic review to examine evidence of associations between clinical leadership and successful information technology (IT) adoption in healthcare organisations.

METHODS: We searched Medline, Embase, Cinahl, and Business Source Premier for articles published between January 2000 to May 2013 with keywords and subject terms related to: (1) the setting--healthcare provider organisations; (2) the technology--health information technology; (3) the process--adoption; and (4) the intervention--leadership. We identified 3121 unique citations, of which 32 met our criteria and were included in the review. Data extracted from the included studies were assessed in light of two frameworks: Bassellier et al.'s IT competence framework; and Avgar et al.'s health IT adoption framework.

RESULTS: The results demonstrate important associations between the attributes of clinical leaders and IT adoption. Clinical leaders who have technical informatics skills and prior experience with IT project management are likely to develop a vision that comprises a long-term commitment to the use of IT. Leaders who possess such a vision believe in the value of IT, are motivated to adopt it, and can maintain confidence and stability through the adversities that IT adoptions often entail. This leads to proactive leadership behaviours and partnerships with IT professionals that are associated with successful organisational and clinical outcomes.

CONCLUSIONS: This review provides evidence that clinical leaders can positively contribute to successful IT adoption in healthcare organisations. Clinical leaders who aim for improvements in the processes and quality of care should cultivate the necessary IT competencies, establish mutual partnerships with IT professionals, and execute proactive IT behaviours to achieve successful IT adoption.}, } @article {pmid24653684, year = {2014}, author = {Padilla, C and Pérez, L and Andrés, P}, title = {Chronic exercise keeps working memory and inhibitory capacities fit.}, journal = {Frontiers in behavioral neuroscience}, volume = {8}, number = {}, pages = {49}, pmid = {24653684}, issn = {1662-5153}, abstract = {Padilla et al. (2013) recently showed that chronic aerobic exercise in young adults is associated with better inhibitory control as measured by the strategic Stop Signal Task (SST). The aim of the current study was to explore whether better inhibitory abilities, associated with high levels of physical fitness, were also associated with higher working memory capacity (WMC) in young healthy adults. Participants aged between 18 and 30 years and showing different levels of fitness confirmed by the Rockport 1-mile walking fitness test took part in this study. Active and passive participants were administered the SST to measure inhibitory control, and the Automatic Operation Span (AOSPAN) to measure verbal WMC. We first replicated Padilla et al.'s results showing that exercise specifically modulates strategic inhibitory processes. Our results also showed that active participants presented with better WMC than sedentary ones, showing a better capacity to manage simultaneously two verbal tasks and to inhibit interference. The results point to an association between chronic exercise, inhibitory abilities, and WMC. The theoretical relationship between these variables will be discussed.}, } @article {pmid24652808, year = {2014}, author = {Hudson, LD and Kennedy, A and Chapman, S}, title = {The trouble with z-scores: response to Faje et al.'s paper: "Fracture risk and areal bone mineral density in adolescent females with anorexia nervosa".}, journal = {The International journal of eating disorders}, volume = {47}, number = {5}, pages = {562}, doi = {10.1002/eat.22262}, pmid = {24652808}, issn = {1098-108X}, mesh = {Anorexia Nervosa/*complications ; *Bone Density ; Female ; Fractures, Bone/*epidemiology ; Humans ; }, } @article {pmid24637572, year = {2014}, author = {Willis, D and Gannon, C and Harlow, T and Baker, I and George, R}, title = {A response to L. Anquinet et al.'s article on terminal sedation.}, journal = {Palliative medicine}, volume = {28}, number = {4}, pages = {367-368}, doi = {10.1177/0269216313513217}, pmid = {24637572}, issn = {1477-030X}, mesh = {*Attitude of Health Personnel ; Caregivers/*psychology ; *Euthanasia ; Female ; Humans ; Hypnotics and Sedatives/*administration & dosage ; Male ; Terminal Care/*psychology ; }, } @article {pmid24634653, year = {2014}, author = {Bancroft, TD and Hogeveen, J and Hockley, WE and Servos, P}, title = {TMS-induced neural noise in sensory cortex interferes with short-term memory storage in prefrontal cortex.}, journal = {Frontiers in computational neuroscience}, volume = {8}, number = {}, pages = {23}, pmid = {24634653}, issn = {1662-5188}, abstract = {In a previous study, Harris et al. (2002) found disruption of vibrotactile short-term memory after applying single-pulse transcranial magnetic stimulation (TMS) to primary somatosensory cortex (SI) early in the maintenance period, and suggested that this demonstrated a role for SI in vibrotactile memory storage. While such a role is compatible with recent suggestions that sensory cortex is the storage substrate for working memory, it stands in contrast to a relatively large body of evidence from human EEG and single-cell recording in primates that instead points to prefrontal cortex as the storage substrate for vibrotactile memory. In the present study, we use computational methods to demonstrate how Harris et al.'s results can be reproduced by TMS-induced activity in sensory cortex and subsequent feedforward interference with memory traces stored in prefrontal cortex, thereby reconciling discordant findings in the tactile memory literature.}, } @article {pmid24588090, year = {2014}, author = {Eastwick, PW and Neff, LA and Finkel, EJ and Luchies, LB and Hunt, LL}, title = {Is a meta-analysis a foundation, or just another brick? Comment on Meltzer, McNulty, Jackson, and Karney (2014).}, journal = {Journal of personality and social psychology}, volume = {106}, number = {3}, pages = {429-434}, doi = {10.1037/a0034767}, pmid = {24588090}, issn = {1939-1315}, mesh = {*Beauty ; Female ; Humans ; Male ; Marriage/*psychology ; *Personal Satisfaction ; Sexual Behavior/*psychology ; }, abstract = {In a longitudinal data set of married couples, Meltzer, McNulty, Jackson, and Karney (2014) reported that partner physical attractiveness is more strongly associated with relationship satisfaction for men than for women. Although a recent meta-analysis (Eastwick, Luchies, Finkel, & Hunt, in press) provided no support for this sex difference across 97 samples and ∼30,000 participants, Meltzer et al. (2014) responded by outlining 7 criteria required for an appropriate test of the sex difference; these criteria eliminate all but 1 study from the meta-analysis. In this commentary, we raise 3 concerns about Meltzer et al.'s contribution. First, there is weak theoretical and empirical support for the criteria they used to dismiss the relevance of the meta-analysis studies. Second, if one adds Meltzer et al.'s data to the meta-analysis, all the sex differences remain extremely small and nonsignificant, even if one focuses only on studies that best conform to Meltzer et al.'s criteria (i.e., married samples, objective attractiveness measures). Third, a new data set meeting all 7 criteria fails to replicate the Meltzer et al. sex difference; in contrast, data revealed that physical attractiveness is, if anything, more strongly associated with the trajectory of relationship satisfaction for women than for men. As noted by Eastwick, Luchies, et al. (in press), in paradigms where participants evaluate partners they have (at a minimum) met face-to-face, the sex difference in the association of physical attractiveness with romantic evaluations is (a) extremely small on average and (b) unlinked to all cross-study characteristics identified to date.}, } @article {pmid24575112, year = {2014}, author = {Perrochon, A and Kemoun, G and Dugué, B and Berthoz, A}, title = {Cognitive Impairment Assessment through Visuospatial Memory Can Be Performed with a Modified Walking Corsi Test Using the 'Magic Carpet'.}, journal = {Dementia and geriatric cognitive disorders extra}, volume = {4}, number = {1}, pages = {1-13}, pmid = {24575112}, issn = {1664-5464}, abstract = {BACKGROUND: Subjects with mild cognitive impairment (MCI) have disturbances in their spatial navigation abilities and exhibit early deficits in visuospatial short-term memory. The purpose of the present study was to determine whether a quantitative (span score) and qualitative (evaluating navigation strategies used) analysis of the Corsi test (usual condition and complex navigation task) would be useful to reveal cognitive decline.

METHODS: We evaluated the performance of 15 young adults, 21 healthy elderly subjects and 15 subjects with MCI using the electronic version of the Corsi test (the Modified Corsi Block-Tapping Test, MCBT) and the complex navigation task (the Modified Walking Corsi Test, MWCT). The MWCT, which is an adaptation of the Corsi test, assesses spatial memory when the subject walks in a complex environment. We used Richard et al.'s model [Cogn Sci 1993;17:497-529] to investigate problem-solving strategies during the Corsi tests.

RESULTS: The span scores obtained on the MCBT and the MWCT were significantly lower in the healthy elderly subjects (MCBT = 5.0 ± 0.7; MWCT = 4.0 ± 0.7) and the subjects with MCI (MCBT = 4.7 ± 0.8; MWCT = 4.1 ± 0.9) than in the younger adults (MCBT = 6.2 ± 0.6; MWCT = 5.3 ± 1.0). The visuospatial working memory was more impaired in the complex navigation task (MWCT = 4.3 ± 0.9) than in the modified Corsi test (MCBT = 5.3 ± 0.8). Finally, the subjects with greater cognitive impairment were more likely to have inadequate or absence of problem-solving strategies.

CONCLUSIONS: Investigating the problem-solving strategies used during the MWCT appears to be a promising way to differentiate between the subjects with MCI and the healthy elderly subjects.}, } @article {pmid24572246, year = {2014}, author = {Zhou, X and Xie, W and Ye, M}, title = {Interaction between social influence and payoff transparency.}, journal = {The Behavioral and brain sciences}, volume = {37}, number = {1}, pages = {104-105}, doi = {10.1017/S0140525X13002501}, pmid = {24572246}, issn = {1469-1825}, mesh = {*Data Collection ; *Decision Making ; Humans ; *Social Behavior ; *Social Networking ; }, abstract = {Social influence and payoff transparency interact with each other to influence decision making. Social influence masks payoff transparency, and lacking transparency drives people to seek social influence. Moreover, our survey supports our claim by showing that social influence and payoff transparency correlate with each other (r(53) = -.71). Bentley et al.'s model can be revised to accommodate the covariance.}, } @article {pmid24572245, year = {2014}, author = {Uhlmann, EL and Silberzahn, R}, title = {Conformity under uncertainty: reliance on gender stereotypes in online hiring decisions.}, journal = {The Behavioral and brain sciences}, volume = {37}, number = {1}, pages = {103-104}, doi = {10.1017/S0140525X13001921}, pmid = {24572245}, issn = {1469-1825}, mesh = {*Data Collection ; *Decision Making ; Humans ; *Social Behavior ; *Social Networking ; }, abstract = {We apply Bentley et al.'s theoretical framework to better understand gender discrimination in online labor markets. Although such settings are designed to encourage employer behavior in the northwest corner of Homo economicus, actual online hiring decisions tend to drift southeast into a "confirmation bias plus weak feedback loops" pattern of discrimination based on inaccurate social stereotypes.}, } @article {pmid24572244, year = {2014}, author = {Taquet, M and Quoidbach, J and de Montjoye, YA and Desseilles, M}, title = {Mapping collective emotions to make sense of collective behavior.}, journal = {The Behavioral and brain sciences}, volume = {37}, number = {1}, pages = {102-103}, doi = {10.1017/S0140525X1300191X}, pmid = {24572244}, issn = {1469-1825}, mesh = {*Data Collection ; *Decision Making ; Humans ; *Social Behavior ; *Social Networking ; }, abstract = {While Bentley et al.'s model is very appealing, in this commentary we argue that researchers interested in big data and collective behavior, including the way humans make decisions, must account for the emotional factor. We investigate how daily choice of activities is influenced by emotions. Results indicate that mood significantly predicts people's decisions about what to do next, stressing the importance of emotional state on decision-making.}, } @article {pmid24572238, year = {2014}, author = {Roesch, EB and Stahl, F and Gaber, MM}, title = {Bigger data for big data: from Twitter to brain-computer interfaces.}, journal = {The Behavioral and brain sciences}, volume = {37}, number = {1}, pages = {97-98}, doi = {10.1017/S0140525X13001854}, pmid = {24572238}, issn = {1469-1825}, mesh = {*Data Collection ; *Decision Making ; Humans ; *Social Behavior ; *Social Networking ; }, abstract = {We are sympathetic with Bentley et al.'s attempt to encompass the wisdom of crowds in a generative model, but posit that a successful attempt at using big data will include more sensitive measurements, more varied sources of information, and will also build from the indirect information available through technology, from ancillary technical features to data from brain-computer interfaces.}, } @article {pmid24572233, year = {2014}, author = {Moat, HS and Preis, T and Olivola, CY and Liu, C and Chater, N}, title = {Using big data to predict collective behavior in the real world.}, journal = {The Behavioral and brain sciences}, volume = {37}, number = {1}, pages = {92-93}, doi = {10.1017/S0140525X13001817}, pmid = {24572233}, issn = {1469-1825}, mesh = {*Data Collection ; *Decision Making ; Humans ; *Social Behavior ; *Social Networking ; }, abstract = {Recent studies provide convincing evidence that data on online information gathering, alongside massive real-world datasets, can give new insights into real-world collective decision making and can even anticipate future actions. We argue that Bentley et al.'s timely account should consider the full breadth, and, above all, the predictive power of big data.}, } @article {pmid24572232, year = {2014}, author = {Mesoudi, A}, title = {Cultural evolution in more than two dimensions: distinguishing social learning biases and identifying payoff structures.}, journal = {The Behavioral and brain sciences}, volume = {37}, number = {1}, pages = {91-92}, doi = {10.1017/S0140525X13001805}, pmid = {24572232}, issn = {1469-1825}, mesh = {*Data Collection ; *Decision Making ; Humans ; *Social Behavior ; *Social Networking ; }, abstract = {Bentley et al.'s two-dimensional conceptual map is complementary to cultural evolution research that has sought to explain population-level cultural dynamics in terms of individual-level behavioral processes. Here, I qualify their scheme by arguing that different social learning biases should be treated distinctly, and that the transparency of decisions is sometimes conflated with the actual underlying payoff structure of those decisions.}, } @article {pmid24572231, year = {2014}, author = {McCain, RA and Hamilton, R}, title = {Coordination games, anti-coordination games, and imitative learning.}, journal = {The Behavioral and brain sciences}, volume = {37}, number = {1}, pages = {90-91}, doi = {10.1017/S0140525X13001799}, pmid = {24572231}, issn = {1469-1825}, mesh = {*Data Collection ; *Decision Making ; Humans ; *Social Behavior ; *Social Networking ; }, abstract = {Bentley et al.'s scheme generates distributions characteristic of situations of high and low social influence on decisions and of high and low salience ("transparency") of rewards. Another element of decisions that may influence the placement of a decision process in their map is the way in which individual decisions interact to determine the payoffs. This commentary discusses the role of Nash equilibria in game theory, focusing especially on coordination and anti-coordination games.}, } @article {pmid24572228, year = {2014}, author = {Keane, MT and Gerow, A}, title = {It's distributions all the way down!: second order changes in statistical distributions also occur.}, journal = {The Behavioral and brain sciences}, volume = {37}, number = {1}, pages = {87}, doi = {10.1017/S0140525X13001763}, pmid = {24572228}, issn = {1469-1825}, mesh = {*Data Collection ; *Decision Making ; Humans ; *Social Behavior ; *Social Networking ; }, abstract = {The textual, big-data literature misses Bentley et al.'s message on distributions; it largely examines the first-order effects of how a single, signature distribution can predict population behaviour, neglecting second-order effects involving distributional shifts, either between signature distributions or within a given signature distribution. Indeed, Bentley et al. themselves under-emphasise the potential richness of the latter, within-distribution effects.}, } @article {pmid24572223, year = {2014}, author = {Fan, JE and Suchow, JW}, title = {The crowd is self-aware.}, journal = {The Behavioral and brain sciences}, volume = {37}, number = {1}, pages = {81-82}, doi = {10.1017/S0140525X13001714}, pmid = {24572223}, issn = {1469-1825}, mesh = {*Data Collection ; *Decision Making ; Humans ; *Social Behavior ; *Social Networking ; }, abstract = {Bentley et al.'s framework assigns phenomena of personal and collective decision-making to regions of a dual-axis map. Here, we propose that understanding the collective dynamics of decision-making requires consideration of factors that guide movement across the map. One such factor is self-awareness, which can lead a group to seek out new knowledge and re-position itself on the map.}, } @article {pmid24572222, year = {2014}, author = {Durlauf, SN}, title = {Modesty can be constructive: linking theory and evidence in social science.}, journal = {The Behavioral and brain sciences}, volume = {37}, number = {1}, pages = {81}, doi = {10.1017/S0140525X13001702}, pmid = {24572222}, issn = {1469-1825}, mesh = {*Data Collection ; *Decision Making ; Humans ; *Social Behavior ; *Social Networking ; }, abstract = {This commentary argues that Bentley et al.'s mapping of shifts in collective human behavior provides a novel vision of how social science theory can inform large data set analysis.}, } @article {pmid24572220, year = {2014}, author = {Buck, R}, title = {Extending the global village: emotional communication in the online age.}, journal = {The Behavioral and brain sciences}, volume = {37}, number = {1}, pages = {79-80}, doi = {10.1017/S0140525X13001684}, pmid = {24572220}, issn = {1469-1825}, mesh = {*Data Collection ; *Decision Making ; Humans ; *Social Behavior ; *Social Networking ; }, abstract = {Bentley et al.'s analysis of how human decision-making has changed in the online age does not mention emotion. Although the suggested dimensions involving social influence and transparency are interesting and suggestive, the engines behind the changes wrought by online media are arguably largely emotional, and implications of the communication of specific emotions via online media need to be better understood.}, } @article {pmid24572219, year = {2014}, author = {Bookstein, FL}, title = {"The map is not the territory".}, journal = {The Behavioral and brain sciences}, volume = {37}, number = {1}, pages = {78-79}, doi = {10.1017/S0140525X13001660}, pmid = {24572219}, issn = {1469-1825}, mesh = {*Data Collection ; *Decision Making ; Humans ; *Social Behavior ; *Social Networking ; }, abstract = {Bentley et al.'s claim that their "map … captures the essence of decision making" (target article, Abstract) is deconstructed and shown to originate in a serious misunderstanding of the role of principal components and statistical graphics in the generation of pattern claims and hypotheses from profile data. Three alternative maps are offered, each with its radiation of further investigations.}, } @article {pmid24572125, year = {2014}, author = {Sudo, K and Taniuchi, S and Takahashi, M and Soejima, K and Hatano, Y and Nakano, K and Shimo, T and Koshino, H and Kaneko, K}, title = {Home-based oral immunotherapy (OIT) with an intermittent loading protocol in children unlikely to outgrow egg allergy.}, journal = {Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology}, volume = {10}, number = {1}, pages = {11}, pmid = {24572125}, issn = {1710-1484}, abstract = {BACKGROUND: Home based oral immunotherapy (OIT) for food allergy has often been used for young children in Japan, the majority of whom are believed to outgrow the allergy by the school age, therefore the true efficacy of the therapy has been controversial. The aim of this study was to evaluate the efficacy and safety of a newly developed slow- type home-based oral immunotherapy (OIT) regimen in children with hen's egg (HE) allergy, who had low likelihood of outgrowing the allergy, with treatment involving only elimination diet.

METHOD: We retrospectively reviewed the medical records of 43 children with egg allergy (30 males; median age 6) who fulfilled Burks et al.'s criteria of being unlikely to outgrow the allergy. Thirty children who agreed to start OIT were assigned to the treatment group, and 13 who did not want to participate immediately were assigned to the untreated group; the patients underwent an elimination diet for 1 year, during which they were monitored. The OIT regimen involved the intake of the maximum tolerated dose 2 to 3 times a week at home, with initial dose introduction followed by dose build-ups with medical supervision. We statistically evaluated the rate of children who changed their threshold up to 32 g of egg - defined as, oral tolerance induction- in both the groups for 1 year and in the OIT group for 2 years, as well as the rate of children who fulfilled Savage et al.'s criteria of clinical tolerance after reaching the abovementioned remission stage.

RESULTS: The rate of children who achieved oral tolerance induction to 32 g of egg after 1 year in the OIT group (9/30) was significantly higher than that in the untreated group (0/13). The total rate within the OIT group was significantly increased from 9/30 at 1 year to 17/30 at two years without any severe adverse reaction; of the above 17 children, we followed 14 children, and noted that 11 of these were able to obtain clinical tolerance.

CONCLUSION: The home-based OIT with an intermittent loading protocol was very safe and effective in children with a low likelihood of outgrowing egg allergy.}, } @article {pmid24565137, year = {2014}, author = {Kelly, K}, title = {The spread of 'Post Abortion Syndrome' as social diagnosis.}, journal = {Social science & medicine (1982)}, volume = {102}, number = {}, pages = {18-25}, doi = {10.1016/j.socscimed.2013.11.030}, pmid = {24565137}, issn = {1873-5347}, mesh = {Abortion, Induced/*psychology ; Dissent and Disputes ; Female ; Humans ; Mental Disorders/*diagnosis ; Pregnancy ; Public Policy ; United States ; }, abstract = {This paper examines the content of Post Abortion Syndrome (PAS) claims, the social actors involved and how this social diagnosis bypassed professional dissent and diffused into public policy in the United States. Previous works on the spread of PAS focus on almost exclusively on anti-abortion think tanks and policymakers. Missing from these analyses, however, is an emphasis on the grassroots-level actions undertaken by evangelical crisis pregnancy center (CPC) activists in introducing and circulating PAS claims. The CPC movement introduced PAS claims and provided the fodder for anti-abortion think tanks to construct evidence of pro-life claims. Despite dissent from health professionals and academic researchers, CPC PAS claims successfully diffused into federal and state abortion policy. I draw upon Brown et al.'s social diagnosis framework and Armstrong's five-stage model of diagnosis development to frame this account.}, } @article {pmid24562372, year = {2015}, author = {Smolker, HR and Depue, BE and Reineberg, AE and Orr, JM and Banich, MT}, title = {Individual differences in regional prefrontal gray matter morphometry and fractional anisotropy are associated with different constructs of executive function.}, journal = {Brain structure & function}, volume = {220}, number = {3}, pages = {1291-1306}, pmid = {24562372}, issn = {1863-2661}, support = {F32 DA034412/DA/NIDA NIH HHS/United States ; P50 MH079485/MH/NIMH NIH HHS/United States ; 1F32DA034412-01A1/DA/NIDA NIH HHS/United States ; P50-079485//PHS HHS/United States ; }, mesh = {Adult ; Anisotropy ; Brain Mapping/*methods ; *Executive Function ; Female ; Gray Matter/*anatomy & histology ; Humans ; Individuality ; *Magnetic Resonance Imaging ; Male ; Prefrontal Cortex/*anatomy & histology ; White Matter/anatomy & histology ; Young Adult ; }, abstract = {Although the relationship between structural differences within the prefrontal cortex (PFC) and executive function (EF) has been widely explored in cognitively impaired populations, little is known about this relationship in healthy young adults. Using optimized voxel-based morphometry (VBM), surface-based morphometry (SBM), and fractional anisotropy (FA) we determined the association between regional PFC grey matter (GM) morphometry and white matter tract diffusivity with performance on tasks that tap different aspects of EF as drawn from Miyake et al.'s three-factor model of EF. Reductions in both GM volume (VBM) and cortical folding (SBM) in the ventromedial PFC (vmPFC), ventrolateral PFC (vlPFC), and dorsolateral PFC (dlPFC) predicted better common EF, shifting-specific, and updating-specific performance, respectively. Despite capturing different components of GM morphometry, voxel- and surface-based findings were highly related, exhibiting regionally overlapping relationships with EF. Increased white matter FA in fiber tracts that connect the vmPFC and vlPFC with posterior regions of the brain also predicted better common EF and shifting-specific performance, respectively. These results suggest that the neural mechanisms supporting distinct aspects of EF may differentially rely on distinct regions of the PFC, and at least in healthy young adults, are influenced by regional morphometry of the PFC and the FA of major white matter tracts that connect the PFC with posterior cortical and subcortical regions.}, } @article {pmid24558973, year = {2014}, author = {Johnson, CN and Crowther, MS and Dickman, CR and Letnic, MI and Newsome, TM and Nimmo, DG and Ritchie, EG and Wallach, AD}, title = {Experiments in no-impact control of dingoes: comment on Allen et al. 2013.}, journal = {Frontiers in zoology}, volume = {11}, number = {1}, pages = {17}, pmid = {24558973}, issn = {1742-9994}, abstract = {There has been much recent debate in Australia over whether lethal control of dingoes incurs environmental costs, particularly by allowing increase of populations of mesopredators such as red foxes and feral cats. Allen et al. (2013) claim to show in their recent study that suppression of dingo activity by poison baiting does not lead to mesopredator release, because mesopredators are also suppressed by poisoning. We show that this claim is not supported by the data and analysis reported in Allen et al.'s paper.}, } @article {pmid24556074, year = {2014}, author = {Edgar, D and Lim, J and Liew, S and Chan, H and Jackson, T and Burrows, S and Wood, F}, title = {Response to Dr Elmasry et al.'s letter to editor.}, journal = {Burns : journal of the International Society for Burn Injuries}, volume = {40}, number = {4}, pages = {773-774}, doi = {10.1016/j.burns.2013.12.009}, pmid = {24556074}, issn = {1879-1409}, mesh = {Burns/*surgery ; Cell Transplantation/*statistics & numerical data ; Female ; Humans ; Length of Stay/*statistics & numerical data ; Male ; *Operative Time ; Skin Transplantation/*statistics & numerical data ; Wound Closure Techniques/*statistics & numerical data ; }, } @article {pmid24533075, year = {2014}, author = {Skule, C and Ulleberg, P and Dallavara Lending, H and Berge, T and Egeland, J and Brennen, T and Landrø, NI}, title = {Depressive symptoms in people with and without alcohol abuse: factor structure and measurement invariance of the Beck Depression Inventory (BDI-II) across groups.}, journal = {PloS one}, volume = {9}, number = {2}, pages = {e88321}, pmid = {24533075}, issn = {1932-6203}, mesh = {Adult ; Alcoholism/*complications/*diagnosis ; Algorithms ; Comorbidity ; Depression/*complications/*diagnosis ; Female ; Humans ; Likelihood Functions ; Male ; Middle Aged ; Psychiatric Status Rating Scales ; Psychometrics ; Reproducibility of Results ; Risk Factors ; Surveys and Questionnaires ; Symptom Assessment ; }, abstract = {This study explored differences in the factor structure of depressive symptoms in patients with and without alcohol abuse, and differences in the severity of depressive symptoms between the two groups. In a sample of 358 patients without alcohol problems and 167 patients with comorbid alcohol problems, confirmatory factor analysis revealed that the same factor structures, Beck et al.'s two-factor Somatic Affective-Cognitive (SA-C) model, and Buckley et al.'s three-factor Cognitive-Affective- Somatic (C-A-S) model, demonstrated the best fit to the data in both groups. The SA-C model was preferred due to its more parsimonious nature. Evidence for strict measurement invariance across the two groups for the SA-C model was found. MIMIC (multiple-indicator-multiple-cause) modeling showed that the level of depressive symptoms was found to be highest on both factors in the group with comorbid alcohol problems. The magnitude of the differences in latent mean scores suggested a moderate difference in the level of depressive symptoms between the two groups. It is argued that patients with comorbid depression and alcohol abuse should be offered parallel and adequate treatment for both conditions.}, } @article {pmid24520173, year = {2014}, author = {Hsiang, SM and Meng, KC}, title = {Reconciling disagreement over climate-conflict results in Africa.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {111}, number = {6}, pages = {2100-2103}, pmid = {24520173}, issn = {1091-6490}, mesh = {*Global Warming ; *Warfare ; }, abstract = {A recent study by Burke et al. [Burke M, Miguel E, Satyanath S, Dykema J, Lobell D (2009) Proc Natl Acad Sci USA 106(49):20670-20674] reports statistical evidence that the likelihood of civil wars in African countries was elevated in hotter years. A following study by Buhaug [Buhaug H (2010) Proc Natl Acad Sci USA 107(38):16477-16482] reports that a reexamination of the evidence overturns Burke et al.'s findings when alternative statistical models and alternative measures of conflict are used. We show that the conclusion by Buhaug is based on absent or incorrect statistical tests, both in model selection and in the comparison of results with Burke et al. When we implement the correct tests, we find there is no evidence presented in Buhaug that rejects the original results of Burke et al.}, } @article {pmid24505721, year = {2013}, author = {Cheng, J and Jiang, T and Deriche, R and Shen, D and Yap, PT}, title = {Regularized spherical polar fourier diffusion MRI with optimal dictionary learning.}, journal = {Medical image computing and computer-assisted intervention : MICCAI ... International Conference on Medical Image Computing and Computer-Assisted Intervention}, volume = {16}, number = {Pt 1}, pages = {639-646}, pmid = {24505721}, support = {R01 EB008374/EB/NIBIB NIH HHS/United States ; R01 EB006733/EB/NIBIB NIH HHS/United States ; R01 AG041721/AG/NIA NIH HHS/United States ; EB008374/EB/NIBIB NIH HHS/United States ; MH100217/MH/NIMH NIH HHS/United States ; MH088520/MH/NIMH NIH HHS/United States ; EB009634/EB/NIBIB NIH HHS/United States ; R01 EB009634/EB/NIBIB NIH HHS/United States ; RC1 MH088520/MH/NIMH NIH HHS/United States ; AG041721/AG/NIA NIH HHS/United States ; EB006733/EB/NIBIB NIH HHS/United States ; R01 MH100217/MH/NIMH NIH HHS/United States ; }, mesh = {*Algorithms ; *Artificial Intelligence ; Brain/*anatomy & histology ; Computer Simulation ; Diffusion Magnetic Resonance Imaging/*methods ; Fourier Analysis ; Humans ; Image Enhancement/methods ; Image Interpretation, Computer-Assisted/*methods ; *Models, Anatomic ; Models, Neurological ; Pattern Recognition, Automated/*methods ; Reproducibility of Results ; Sensitivity and Specificity ; }, abstract = {Compressed Sensing (CS) takes advantage of signal sparsity or compressibility and allows superb signal reconstruction from relatively few measurements. Based on CS theory, a suitable dictionary for sparse representation of the signal is required. In diffusion MRI (dMRI), CS methods proposed for reconstruction of diffusion-weighted signal and the Ensemble Average Propagator (EAP) utilize two kinds of Dictionary Learning (DL) methods: 1) Discrete Representation DL (DR-DL), and 2) Continuous Representation DL (CR-DL). DR-DL is susceptible to numerical inaccuracy owing to interpolation and regridding errors in a discretized q-space. In this paper, we propose a novel CR-DL approach, called Dictionary Learning - Spherical Polar Fourier Imaging (DL-SPFI) for effective compressed-sensing reconstruction of the q-space diffusion-weighted signal and the EAP. In DL-SPFI, a dictionary that sparsifies the signal is learned from the space of continuous Gaussian diffusion signals. The learned dictionary is then adaptively applied to different voxels using a weighted LASSO framework for robust signal reconstruction. Compared with the start-of-the-art CR-DL and DR-DL methods proposed by Merlet et al. and Bilgic et al., respectively, our work offers the following advantages. First, the learned dictionary is proved to be optimal for Gaussian diffusion signals. Second, to our knowledge, this is the first work to learn a voxel-adaptive dictionary. The importance of the adaptive dictionary in EAP reconstruction will be demonstrated theoretically and empirically. Third, optimization in DL-SPFI is only performed in a small subspace resided by the SPF coefficients, as opposed to the q-space approach utilized by Merlet et al. We experimentally evaluated DL-SPFI with respect to L1-norm regularized SPFI (L1-SPFI), which uses the original SPF basis, and the DR-DL method proposed by Bilgic et al. The experiment results on synthetic and real data indicate that the learned dictionary produces sparser coefficients than the original SPF basis and results in significantly lower reconstruction error than Bilgic et al.'s method.}, } @article {pmid24491372, year = {2014}, author = {Paneroni, M and Trainini, D and Winck, JC and Vitacca, M}, title = {Pilot study for home monitoring of cough capacity in amyotrophic lateral sclerosis: A case series.}, journal = {Revista portuguesa de pneumologia}, volume = {20}, number = {4}, pages = {181-187}, doi = {10.1016/j.rppneu.2013.11.003}, pmid = {24491372}, issn = {2172-6825}, mesh = {Amyotrophic Lateral Sclerosis/*physiopathology/therapy ; *Cough ; Female ; Humans ; Male ; Middle Aged ; Monitoring, Physiologic ; Pilot Projects ; *Self Care ; }, abstract = {BACKGROUND: Cough capacity derangement is associated with a high risk of pulmonary complications in amyotrophic lateral sclerosis patients when cough assistance is not routinely performed at home. The primary aim of this study was to evaluate the feasibility of a long-term home based daily self-monitoring cough capacity.

METHODS: Eighteen subjects were enrolled in a 9-month study at home. Changes in peak cough expiratory flow, oxygen saturation, respiratory discomfort and incidence of respiratory deterioration events were evaluated. In subjects presenting respiratory deterioration events, decline in the abovementioned respiratory variables was evaluated (#NCT00613899).

RESULTS: During an average follow-up of 125±102 days, a total of 1175 measures were performed on 12 subjects. Mean compliance to proposed evaluations was 37±32% which worsened over time. Peak cough expiratory flow decreased by 15.08±32.43L/min monthly. Five subjects reported 6 episodes of respiratory deterioration events, after a mean period of 136±108 days. They had poor respiratory function and more years of disease. There was no difference in peak cough expiratory flow and its decline whether subjects presented respiratory deterioration events or not. In 4 subjects the respiratory discomfort score significantly worsened after respiratory deterioration events from 3.0±1.41 to 4.25±1.71.

CONCLUSION: Daily self-monitoring of peak cough expiratory flow, oxygen saturation and respiratory discomfort seems difficult to obtain because of poor adherence to measures; this protocol does not seem to add anything to current practice of advising on clinical derangements. Confirmatory larger studies are necessary.}, } @article {pmid24467949, year = {2013}, author = {Lan, Y and Kriete, A and Rosen, GL}, title = {Selecting age-related functional characteristics in the human gut microbiome.}, journal = {Microbiome}, volume = {1}, number = {1}, pages = {2}, pmid = {24467949}, issn = {2049-2618}, abstract = {BACKGROUND: Human gut microbial functions are often associated with various diseases and host physiologies. Aging, a less explored factor, is also suspected to affect or be affected by microbiome alterations. By combining functional feature selection with supervised classification, we aim to facilitate identification of age-related functional characteristics in metagenomes from several human gut microbiome studies (MetaHIT, MicroAge, MicroObes, Kurokawa et al.'s and Gill et al.'s dataset).

RESULTS: We apply two feature selection methods, term frequency-inverse document frequency (TF-iDF) and minimum-redundancy maximum-relevancy (mRMR), to identify functional signatures that differentiate metagenomes by age. After features are reduced, we use a support vector machine (SVM) to predict host age of new metagenomes. Functional features are from protein families (Pfams), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, KEGG ontologies and the Gene Ontology (GO) database. Initial investigations demonstrate that ordination of the functional principal components shows great overlap between different age groups. However, when feature selection is applied, mRMR tightens the ordination cluster for each age group, and TF-iDF offers better linear separation. Both TF-iDF and mRMR were used in conjunction with a SVM classifier and achieved areas under receiver operating characteristic curves (AUCs) 10 to 15% above chance to classify individuals above/below mid-ages (about 38 to 43 years old) using Pfams. Better performance around mid-ages is also observed when using other functional categories and age-balanced dataset. We also identified some age-related Pfams that improved age discrimination at age 65 with another feature selection method called LEfSe, on an age-balanced dataset. The selected functional characteristics identify a broad range of age-relevant metabolisms, such as reduced vitamin B12 synthesis, reduced activity of reductases, increased DNA damage, occurrences of stress responses and immune system compromise, and upregulated glycosyltransferases in the aging population.

CONCLUSIONS: Feature selection can yield biologically meaningful results when used in conjunction with classification, and makes age classification of new human gut metagenomes feasible. While we demonstrate the promise of this approach, the data-dependent prediction performance could be further improved. We hypothesize that while the Qin et al. dataset is the most comprehensive to date, even deeper sampling is needed to better characterize and predict the microbiomes' functional content.}, } @article {pmid24465367, year = {2014}, author = {Wu, S and Sun, Q}, title = {Computer simulation of leadership, consensus decision making and collective behaviour in humans.}, journal = {PloS one}, volume = {9}, number = {1}, pages = {e80680}, pmid = {24465367}, issn = {1932-6203}, mesh = {*Computer Simulation ; *Consensus ; *Cooperative Behavior ; *Decision Making ; Humans ; *Leadership ; Time Factors ; }, abstract = {The aim of this study is to evaluate the reliability of a crowd simulation model developed by the authors by reproducing Dyer et al.'s experiments (published in Philosophical Transactions in 2009) on human leadership and consensus decision making in a computer-based environment. The theoretical crowd model of the simulation environment is presented, and its results are compared and analysed against Dyer et al.'s original experiments. It is concluded that the simulation results are largely consistent with the experiments, which demonstrates the reliability of the crowd model. Furthermore, the simulation data also reveals several additional new findings, namely: 1) the phenomena of sacrificing accuracy to reach a quicker consensus decision found in ants colonies was also discovered in the simulation; 2) the ability of reaching consensus in groups has a direct impact on the time and accuracy of arriving at the target position; 3) the positions of the informed individuals or leaders in the crowd could have significant impact on the overall crowd movement; and 4) the simulation also confirmed Dyer et al.'s anecdotal evidence of the proportion of the leadership in large crowds and its effect on crowd movement. The potential applications of these findings are highlighted in the final discussion of this paper.}, } @article {pmid24451393, year = {2014}, author = {Aubert, N and Mosca, C and Fujii, T and Hagiya, M and Rondelez, Y}, title = {Computer-assisted design for scaling up systems based on DNA reaction networks.}, journal = {Journal of the Royal Society, Interface}, volume = {11}, number = {93}, pages = {20131167}, pmid = {24451393}, issn = {1742-5662}, mesh = {*Algorithms ; *Computers, Molecular ; *DNA ; *Models, Theoretical ; }, abstract = {In the past few years, there have been many exciting advances in the field of molecular programming, reaching a point where implementation of non-trivial systems, such as neural networks or switchable bistable networks, is a reality. Such systems require nonlinearity, be it through signal amplification, digitalization or the generation of autonomous dynamics such as oscillations. The biochemistry of DNA systems provides such mechanisms, but assembling them in a constructive manner is still a difficult and sometimes counterintuitive process. Moreover, realistic prediction of the actual evolution of concentrations over time requires a number of side reactions, such as leaks, cross-talks or competitive interactions, to be taken into account. In this case, the design of a system targeting a given function takes much trial and error before the correct architecture can be found. To speed up this process, we have created DNA Artificial Circuits Computer-Assisted Design (DACCAD), a computer-assisted design software that supports the construction of systems for the DNA toolbox. DACCAD is ultimately aimed to design actual in vitro implementations, which is made possible by building on the experimental knowledge available on the DNA toolbox. We illustrate its effectiveness by designing various systems, from Montagne et al.'s Oligator or Padirac et al.'s bistable system to new and complex networks, including a two-bit counter or a frequency divider as well as an example of very large system encoding the game Mastermind. In the process, we highlight a variety of behaviours, such as enzymatic saturation and load effect, which would be hard to handle or even predict with a simpler model. We also show that those mechanisms, while generally seen as detrimental, can be used in a positive way, as functional part of a design. Additionally, the number of parameters included in these simulations can be large, especially in the case of complex systems. For this reason, we included the possibility to use CMA-ES, a state-of-the-art optimization algorithm that will automatically evolve parameters chosen by the user to try to match a specified behaviour. Finally, because all possible functionality cannot be captured by a single software, DACCAD includes the possibility to export a system in the synthetic biology markup language, a widely used language for describing biological reaction systems. DACCAD can be downloaded online at http://www.yannick-rondelez.com/downloads/.}, } @article {pmid24447383, year = {2014}, author = {Upton, D and Upton, P and Scurlock-Evans, L}, title = {The reach, transferability, and impact of the Evidence-Based Practice Questionnaire: a methodological and narrative literature review.}, journal = {Worldviews on evidence-based nursing}, volume = {11}, number = {1}, pages = {46-54}, doi = {10.1111/wvn.12019}, pmid = {24447383}, issn = {1741-6787}, mesh = {Attitude of Health Personnel ; Evidence-Based Nursing/*standards ; *Health Knowledge, Attitudes, Practice ; Humans ; Nursing Staff/psychology/*standards ; Psychometrics/*standards ; Reproducibility of Results ; Surveys and Questionnaires/*standards ; }, abstract = {BACKGROUND: Since the 1990s, evidence-based practice (EBP) has been increasingly emphasized in nursing, but its implementation is still sometimes met with confusion and resistance. Therefore, identifying factors affecting its implementation is crucial. The Evidence-Based Practice Questionnaire (EBPQ) was published in 2006, addressing a need for a robust measure of nurses' practice of, attitudes toward, and knowledge of EBP. The growing body of professionals using the questionnaire means that a review of its reach, transferability, and impact is timely.

AIMS: The aims of this review were threefold: (a) identify the situations in which the EBPQ has been used in both published and unpublished research internationally (Reach); (b) collate the psychometric properties of the EBPQ from the research reviewed (Transferability); and (c) discuss the study's findings to shed new light on issues facing professionals in implementing EBP, and possible future directions for research (Impact).

METHODS: Literature searches on studies reported between 2006 and July 2012 inclusive were conducted using the terms "Evidence-Based Practice Questionnaire" and "EBPQ." Green, Johnson and Adams's guidelines for completing narrative literature reviews and Terwee et al.'s framework for reporting questionnaires' psychometric properties were adopted to ensure rigor.

FINDINGS: Twenty-seven studies were reviewed in which the EBPQ had been translated into five different languages and used with a variety of professional groups. The questionnaire demonstrated convergent and discriminant validity and good internal reliability. Research adopting the questionnaire identified a range of variables related to EBP implementation, including qualification route and job role.

LINKING EVIDENCE TO ACTION: Assessment of organizational culture and workforce training needs prior to developing educational interventions is crucial. The EBPQ has the potential to provide further understanding of these and other issues faced by professionals when implementing EBP.}, } @article {pmid24443812, year = {2014}, author = {McGill, B and Moulds, ML}, title = {Characteristics of autobiographical memories and prospective imagery across a spectrum of hypomanic personality traits.}, journal = {Memory (Hove, England)}, volume = {22}, number = {8}, pages = {1139-1148}, doi = {10.1080/09658211.2013.873808}, pmid = {24443812}, issn = {1464-0686}, mesh = {Adolescent ; Adult ; Emotions ; Female ; Humans ; *Imagination ; Male ; *Memory, Episodic ; Neuropsychological Tests ; *Personality ; Personality Disorders/*psychology ; Personality Tests ; Psychiatric Status Rating Scales ; Young Adult ; }, abstract = {Evidence of a strong causal relationship between mental imagery and emotion has informed psychological conceptualisations of disordered positive mood states (i.e., mania). Holmes et al.'s cognitive model of bipolar disorder asserts a prominent role for intrusive and affect-laden positive imagery of the past and the future in the amplification and maintenance of positive mood and associated manic behaviours. The aims of the current study were two-fold: (1) to test aspects of this model in a non-clinical population sampled for hypomanic personality traits and (2) to examine the phenomenological characteristics of positive autobiographical memories and imagery of the future. Undergraduate students (N = 80) completed a battery of self-report questionnaires and rated their positive and negative memories and images of the future on a number of dimensions. We found significant positive correlations between hypomanic tendencies and the (1) everyday experience and use of mental imagery, (2) experience of intrusive mental imagery of future events, (3) emotional intensity and sensory detail of positive but not negative autobiographical memories. Results are discussed in the context of their theoretical and clinical implications, and directions for future research are considered.}, } @article {pmid24438534, year = {2014}, author = {Gathercole, SE}, title = {Commentary: Working memory training and ADHD - where does its potential lie? Reflections on Chacko et al. (2014).}, journal = {Journal of child psychology and psychiatry, and allied disciplines}, volume = {55}, number = {3}, pages = {256-257}, doi = {10.1111/jcpp.12196}, pmid = {24438534}, issn = {1469-7610}, support = {MC_UP_A060_1104/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Attention Deficit Disorder with Hyperactivity/*therapy ; Cognitive Behavioral Therapy/*methods ; Female ; Humans ; Male ; Memory, Short-Term/*physiology ; }, abstract = {Chacko et al.'s investigation of the clinical utility of WM training to alleviate key symptoms of ADHD is timely and substantial, and marks a significant point in cognitive training research. Cogmed Working Memory Training (CWMT) involves intensive practice on multiple memory span tasks that increase in difficulty as performance improves with practice. Relative to a placebo version in which the span level of the memory tasks are kept at a low fixed level, Chacko et al. () found that CWMT boosted the performance of children with ADHD on short-term memory (STM) tasks similar to trained activities. Complex WM span measures sharing little overlap with the structure of training activities were not enhanced. Neither did active CWMT ameliorate classic symptoms of ADHD such as parent or teacher ratings of attentional problems, or direct measures of motor impulsivity and sustained attention. Reading, spelling, comprehension or mathematics scores similarly showed no response to training.}, } @article {pmid24435984, year = {2014}, author = {Li, F and Huo, H and Xiao, Y and Xing, W and Xia, H and Yang, X}, title = {Letter regarding Liu et al.'s study entitled "A systematic review with meta-analysis of posterior interbody fusion versus posterolateral fusion in lumbar spondylolisthesis".}, journal = {European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society}, volume = {23}, number = {4}, pages = {933-934}, pmid = {24435984}, issn = {1432-0932}, mesh = {Humans ; Lumbar Vertebrae/*surgery ; Spinal Fusion/*methods ; Spondylolisthesis/*surgery ; }, } @article {pmid24430709, year = {2014}, author = {Lowe, DT}, title = {Comment on Dorniak-Wall et al.'s paper on L-arginine for pre-eclampsia.}, journal = {Journal of human hypertension}, volume = {28}, number = {4}, pages = {282}, pmid = {24430709}, issn = {1476-5527}, mesh = {Arginine/*therapeutic use ; Female ; Humans ; Pre-Eclampsia/*drug therapy/*prevention & control ; Pregnancy ; Pregnancy Complications, Cardiovascular/*drug therapy/*prevention & control ; }, } @article {pmid24428273, year = {2016}, author = {Zoëga, S and Gunnarsdottir, S and Wilson, ME and Gordon, DB}, title = {Quality Pain Management in Adult Hospitalized Patients: A Concept Evaluation.}, journal = {Nursing forum}, volume = {51}, number = {1}, pages = {3-12}, doi = {10.1111/nuf.12085}, pmid = {24428273}, issn = {1744-6198}, mesh = {Adult ; Hospitalization ; Humans ; Nursing Evaluation Research ; Pain Management/*standards ; Practice Guidelines as Topic ; Quality Improvement/*standards ; Quality of Health Care/*standards ; Quality of Life ; Terminology as Topic ; }, abstract = {AIM: To explore the concept of quality pain management (QPM) in adult hospitalized patients.

BACKGROUND: Pain is common in hospitalized patients, and pain management remains suboptimal in some settings.

DESIGN: A concept evaluation based on Morse et al.'s method.

DATA SOURCE: Of more than 5,000 articles found, data were restricted to 37 selected key articles published in peer-reviewed journals.

REVIEW METHODS: Data were extracted from the selected articles and then synthesized according to the following: definition, characteristics, boundaries, preconditions, and outcomes.

RESULTS: QPM relates to the Structure: organizationally supported evidence-based policies, competent staff, interprofessional and specialized care, and staff accountability;

PROCESS: screening, assessment/reassessment and communication of pain and its treatment, patient/family education, individualized evidence-based treatment, embedded in safe, effective, patient-centered, timely, efficient, and equitable services; and

OUTCOMES: reduced pain severity and functional interference, decreased prevalence/severity of adverse consequences from pain or pain treatment, and increase in patient satisfaction.

CONCLUSIONS: QPM is a multifaceted concept that remains poorly defined in the literature. Studies should aim to develop valid, reliable, and operational measures of the pillars of QPM and to look at the relationship among these factors. Authors need to state how they define and what aspects of QPM they are measuring.}, } @article {pmid24423394, year = {2014}, author = {Huijg, JM and Gebhardt, WA and Crone, MR and Dusseldorp, E and Presseau, J}, title = {Discriminant content validity of a theoretical domains framework questionnaire for use in implementation research.}, journal = {Implementation science : IS}, volume = {9}, number = {}, pages = {11}, pmid = {24423394}, issn = {1748-5908}, mesh = {*Attitude of Health Personnel ; *Diffusion of Innovation ; Environment ; Evidence-Based Medicine ; Health Knowledge, Attitudes, Practice ; Language ; *Models, Theoretical ; Motivation ; Professional Role ; Reproducibility of Results ; Self Efficacy ; Surveys and Questionnaires ; Translational Research, Biomedical/*methods ; }, abstract = {BACKGROUND: To improve the implementation of innovations in healthcare settings, it is important to understand factors influencing healthcare professionals' behaviors. We aimed to develop a generic questionnaire in English and in Dutch assessing the 14 domains of behavioral determinants from the revised TDF (Cane et al., 2012) that can be tailored to suit different targets, actions, contexts, and times of interest, and to investigate questionnaire items' discriminant content validity.

METHODS: We identified existing questionnaires including items assessing constructs within TDF domains and developed new items where needed. Nineteen judges allocated 79 items to one or more TDF domains. One-sample t-tests were used to examine the discriminant content validity of each item, i.e., whether items measured intended domains or whether items measured a combination of domains.

RESULTS: We identified items judged to discriminately measure 11 out of 14 domains. Items measuring the domains Reinforcement, Goals, and Behavioral regulation were judged to measure a combination of domains.

CONCLUSIONS: We have developed a questionnaire in English and in Dutch able to discriminately assess the majority of TDF domains. The results partly support Cane et al.'s (2012) 14-domain validation of the TDF and suggest that Michie et al.'s (2005) 12-domain original version might be more applicable in developing a TDF-based questionnaire. The identified items provide a robust basis for developing a questionnaire to measure TDF-based determinants of healthcare professionals' implementation behaviors to suit different targets, actions, contexts, and times. Future research should investigate the concurrent and predictive validity and reliability of such a questionnaire in practice.}, } @article {pmid24411945, year = {2014}, author = {Knight, KR and Lopez, AM and Comfort, M and Shumway, M and Cohen, J and Riley, ED}, title = {Single room occupancy (SRO) hotels as mental health risk environments among impoverished women: the intersection of policy, drug use, trauma, and urban space.}, journal = {The International journal on drug policy}, volume = {25}, number = {3}, pages = {556-561}, pmid = {24411945}, issn = {1873-4758}, support = {R01 DA015605/DA/NIDA NIH HHS/United States ; }, mesh = {Anthropology, Cultural ; Diagnosis, Dual (Psychiatry) ; Female ; Housing/economics/*statistics & numerical data ; Humans ; Illicit Drugs ; Mental Disorders/economics/*epidemiology ; Mental Health ; Poverty ; *Public Policy ; Quality of Life ; Risk ; San Francisco/epidemiology ; Substance-Related Disorders/economics/*epidemiology ; }, abstract = {BACKGROUND: Due to the significantly high levels of comorbid substance use and mental health diagnosis among urban poor populations, examining the intersection of drug policy and place requires a consideration of the role of housing in drug user mental health. In San Francisco, geographic boundedness and progressive health and housing polices have coalesced to make single room occupancy hotels (SROs) a key urban built environment used to house poor populations with co-occurring drug use and mental health issues. Unstably housed women who use illicit drugs have high rates of lifetime and current trauma, which manifests in disproportionately high rates of post-traumatic stress disorder (PTSD), anxiety, and depression when compared to stably housed women.

METHODS: We report data from a qualitative interview study (n=30) and four years of ethnography conducted with housing policy makers and unstably housed women who use drugs and live in SROs.

RESULTS: Women in the study lived in a range of SRO built environments, from publicly funded, newly built SROs to privately owned, dilapidated buildings, which presented a rich opportunity for ethnographic comparison. Applying Rhodes et al.'s framework of socio-structural vulnerability, we explore how SROs can operate as "mental health risk environments" in which macro-structural factors (housing policies shaping the built environment) interact with meso-level factors (social relations within SROs) and micro-level, behavioral coping strategies to impact women's mental health. The degree to which SRO built environments were "trauma-sensitive" at the macro level significantly influenced women's mental health at meso- and micro-levels. Women who were living in SROs which exacerbated fear and anxiety attempted, with limited success, to deploy strategies on the meso- and micro-level to manage their mental health symptoms.

CONCLUSION: Study findings underscore the importance of housing polices which consider substance use in the context of current and cumulative trauma experiences in order to improve quality of life and mental health for unstably housed women.}, } @article {pmid24407298, year = {2013}, author = {Catanzaro, D and Labbé, M and Halldórsson, BV}, title = {An integer programming formulation of the parsimonious loss of heterozygosity problem.}, journal = {IEEE/ACM transactions on computational biology and bioinformatics}, volume = {10}, number = {6}, pages = {1391-1402}, doi = {10.1109/TCBB.2012.138}, pmid = {24407298}, issn = {1557-9964}, mesh = {Algorithms ; Computational Biology/*methods ; Gene Deletion ; Genome, Human ; Genome-Wide Association Study ; Heterozygote ; Humans ; *Loss of Heterozygosity ; *Models, Genetic ; Polymorphism, Genetic ; Polymorphism, Single Nucleotide ; Recombination, Genetic ; Sequence Homology, Nucleic Acid ; Software ; }, abstract = {A loss of heterozygosity (LOH) event occurs when, by the laws of Mendelian inheritance, an individual should be heterozygote at a given site but, due to a deletion polymorphism, is not. Deletions play an important role in human disease and their detection could provide fundamental insights for the development of new diagnostics and treatments. In this paper, we investigate the parsimonious loss of heterozygosity problem (PLOHP), i.e., the problem of partitioning suspected polymorphisms from a set of individuals into a minimum number of deletion areas. Specifically, we generalize Halldórsson et al.'s work by providing a more general formulation of the PLOHP and by showing how one can incorporate different recombination rates and prior knowledge about the locations of deletions. Moreover, we show that the PLOHP can be formulated as a specific version of the clique partition problem in a particular class of graphs called undirected catch-point interval graphs and we prove its general $({\cal NP} )$-hardness. Finally, we provide a state-of-the-art integer programming (IP) formulation and strengthening valid inequalities to exactly solve real instances of the PLOHP containing up to 9,000 individuals and 3,000 SNPs. Our results give perspectives on the mathematics of the PLOHP and suggest new directions on the development of future efficient exact solution approaches.}, } @article {pmid24387154, year = {2014}, author = {Frawley, G and Shand, J and Heggie, A}, title = {Rebuttal to Breugem et al.'s comment on Anesthetic implications of infants with mandibular hypoplasia treated with mandibular distraction osteogenesis.}, journal = {Paediatric anaesthesia}, volume = {24}, number = {2}, pages = {228-229}, doi = {10.1111/pan.12313}, pmid = {24387154}, issn = {1460-9592}, mesh = {*Anesthesia, Inhalation ; Female ; Humans ; Male ; Mandibular Diseases/*surgery ; Osteogenesis, Distraction/*methods ; }, } @article {pmid24383445, year = {2014}, author = {Yang, CS and Hung, KC and Huang, YM and Hsu, WM}, title = {Response to Carifi et al.'s letter.}, journal = {Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics}, volume = {30}, number = {4}, pages = {304-305}, doi = {10.1089/jop.2013.0217.rs}, pmid = {24383445}, issn = {1557-7732}, mesh = {Angiogenesis Inhibitors/*therapeutic use ; Antibodies, Monoclonal, Humanized/*therapeutic use ; Diabetic Retinopathy/*therapy ; Female ; Humans ; Light Coagulation/*methods ; Male ; Retinal Neovascularization/*therapy ; Vitreous Hemorrhage/*therapy ; }, } @article {pmid24374471, year = {2014}, author = {Cevik, L and Karaca, RO and Babaoglu, MO}, title = {Letter to the editor regarding 'Youssef et al.'s multi-drug resistance-1 gene polymorphisms in nephrotic syndrome: impact on susceptibility and response to steroids'.}, journal = {Gene}, volume = {537}, number = {1}, pages = {174}, doi = {10.1016/j.gene.2013.12.042}, pmid = {24374471}, issn = {1879-0038}, mesh = {ATP Binding Cassette Transporter, Subfamily B, Member 1/*genetics ; Female ; Humans ; Kidney/*metabolism ; Male ; Nephrotic Syndrome/*genetics ; *Polymorphism, Single Nucleotide ; Steroids/*therapeutic use ; }, } @article {pmid24372753, year = {2014}, author = {Sumner, S}, title = {The importance of genomic novelty in social evolution.}, journal = {Molecular ecology}, volume = {23}, number = {1}, pages = {26-28}, doi = {10.1111/mec.12580}, pmid = {24372753}, issn = {1365-294X}, mesh = {Animals ; Ants/*genetics ; *Behavior, Animal ; Female ; Reproduction/*genetics ; *Social Dominance ; }, abstract = {Insect societies dominate the natural world: They mould landscapes, sculpt habitats, pollinate plants, sow seeds and control pests. The secret to their success lies in the evolution of queen (reproductive) and worker (provisioner and carer) castes (Oster & Wilson 1978). A major problem in evolutionary biology is explaining the evolution of insect castes, particularly the workers (Darwin 1859). Next-generation sequencing technologies now make it possible to understand how genomic material is born, lost and reorganized in the evolution of alternative phenotypes. Such analyses are revealing a general role for novel (e.g. taxonomically restricted) genes in phenotypic innovations across the animal kingdom (Chen et al. 2013). In this issue of molecular ecology, Feldmeyer et al. (2014) provide overwhelming evidence for the importance of novel genes in caste evolution in an ant. Feldmeyer et al.'s study is important and exciting because it cements the role of genomic novelty, as well as conservation, firmly into the molecular jigsaw of social evolution. Evolution is eclectic in its exploitation of both old and new genomic material to generate replicated phenotypic innovations across the tree of life.}, } @article {pmid24354952, year = {2014}, author = {Ramsay, P and Huby, G and Thompson, A and Walsh, T}, title = {Intensive care survivors' experiences of ward-based care: Meleis' theory of nursing transitions and role development among critical care outreach services.}, journal = {Journal of clinical nursing}, volume = {23}, number = {5-6}, pages = {605-615}, doi = {10.1111/jocn.12452}, pmid = {24354952}, issn = {1365-2702}, mesh = {Aged ; *Critical Care ; Female ; Humans ; *Intensive Care Units ; Male ; Middle Aged ; *Nurse's Role ; *Nursing Theory ; *Survivors ; }, abstract = {AIMS AND OBJECTIVES: To explore the psychosocial needs of patients discharged from intensive care, the extent to which they are captured using existing theory on transitions in care and the potential role development of critical care outreach, follow-up and liaison services.

BACKGROUND: Intensive care patients are at an increased risk of adverse events, deterioration or death following ward transfer. Nurse-led critical care outreach, follow-up or liaison services have been adopted internationally to prevent these potentially avoidable sequelae. The need to provide patients with psychosocial support during the transition to ward-based care has also been identified, but the evidence base for role development is currently limited.

DESIGN AND METHODS: Twenty participants were invited to discuss their experiences of ward-based care as part of a broader study on recovery following prolonged critical illness. Psychosocial distress was a prominent feature of their accounts, prompting secondary data analysis using Meleis et al.'s mid-range theory on experiencing transitions.

RESULTS: Participants described a sense of disconnection in relation to profound debilitation and dependency and were often distressed by a perceived lack of understanding, indifference or insensitivity among ward staff to their basic care needs. Negotiating the transition between dependence and independence was identified as a significant source of distress following ward transfer. Participants varied in the extent to which they were able to express their needs and negotiate recovery within professionally mediated boundaries.

CONCLUSION: These data provide new insights into the putative origins of the psychosocial distress that patients experience following ward transfer.

Meleis et al.'s work has resonance in terms of explicating intensive care patients' experiences of psychosocial distress throughout the transition to general ward-based care, such that the future role development of critical care outreach, follow-up and liaison services may be more theoretically informed.}, } @article {pmid24352826, year = {2014}, author = {Lan, X}, title = {Reply to comment on Lan et al.: S-osteotomy with lengthening and then nailing compared with traditional Ilizarov method.}, journal = {International orthopaedics}, volume = {38}, number = {3}, pages = {679}, pmid = {24352826}, issn = {1432-5195}, mesh = {Bone Lengthening/*methods ; *Bone Nails ; Female ; Humans ; *Ilizarov Technique ; Leg Length Inequality/*surgery ; Male ; Osteotomy/*methods ; Tibia/*surgery ; }, } @article {pmid24349180, year = {2013}, author = {Ortuño-Sierra, J and Badoud, D and Knecht, F and Paino, M and Eliez, S and Fonseca-Pedrero, E and Debbané, M}, title = {Testing measurement invariance of the schizotypal personality questionnaire-brief scores across Spanish and Swiss adolescents.}, journal = {PloS one}, volume = {8}, number = {12}, pages = {e82041}, pmid = {24349180}, issn = {1932-6203}, mesh = {Adolescent ; Analysis of Variance ; Female ; Humans ; Male ; Psychometrics ; Schizotypal Personality Disorder/diagnosis/*physiopathology/psychology ; Spain ; Surveys and Questionnaires ; Switzerland ; }, abstract = {BACKGROUND: Schizotypy is a complex construct intimately related to psychosis. Empirical evidence indicates that participants with high scores on schizotypal self-report are at a heightened risk for the later development of psychotic disorders. Schizotypal experiences represent the behavioural expression of liability for psychotic disorders. Previous factorial studies have shown that schizotypy is a multidimensional construct similar to that found in patients with schizophrenia. Specifically, using the Schizotypal Personality Questionnaire-Brief (SPQ-B), the three-dimensional model has been widely replicated. However, there has been no in-depth investigation of whether the dimensional structure underlying the SPQ-B scores is invariant across countries.

METHODS: The main goal of this study was to examine the measurement invariance of the SPQ-B scores across Spanish and Swiss adolescents. The final sample was made up of 261 Spanish participants (51.7% men; M = 16.04 years) and 241 Swiss participants (52.3% men; M = 15.94 years).

RESULTS: The results indicated that Raine et al.'s three-factor model presented adequate goodness-of-fit indices. Moreover, the results supported the measurement invariance (configural and partial strong invariance) of the SPQ-B scores across the two samples. Spanish participants scored higher on Interpersonal dimension than Swiss when latent means were compared.

DISCUSSION: The study of measurement equivalence across countries provides preliminary evidence for the Raine et al.'s three-factor model and of the cross-cultural validity of the SPQ-B scores in adolescent population. Future studies should continue to examine the measurement invariance of the schizotypy and psychosis-risk syndromes across cultures.}, } @article {pmid24346513, year = {2014}, author = {Elhence, A and Jalan, D and Talreja, H}, title = {Comment on Lan et al.: S-osteotomy with lengthening and then nailing compared with traditional Ilizarov method.}, journal = {International orthopaedics}, volume = {38}, number = {3}, pages = {677}, pmid = {24346513}, issn = {1432-5195}, mesh = {Bone Lengthening/*methods ; *Bone Nails ; Female ; Humans ; *Ilizarov Technique ; Leg Length Inequality/*surgery ; Male ; Osteotomy/*methods ; Tibia/*surgery ; }, } @article {pmid24345630, year = {2014}, author = {Asthana, S and Dasgupta, R}, title = {Rao et al.'s "Which doctor for primary health care? Quality of care and non-physician clinicians in India 84 (2013) 30-34".}, journal = {Social science & medicine (1982)}, volume = {102}, number = {}, pages = {201-202}, doi = {10.1016/j.socscimed.2013.11.044}, pmid = {24345630}, issn = {1873-5347}, mesh = {Allied Health Personnel/*standards ; Clinical Competence/*statistics & numerical data ; Female ; Humans ; Male ; Physicians, Primary Care/*standards ; Primary Health Care/*organization & administration ; *Quality of Health Care ; }, } @article {pmid24339616, year = {2013}, author = {Umamaheshwar, KL and Sehrawat, A and Parashar, MK and Mavade, K}, title = {Two case reports of an unusual association between Klippel-Feil syndrome and amyotrophic lateral sclerosis: Do they share same genetic defect?.}, journal = {Annals of Indian Academy of Neurology}, volume = {16}, number = {4}, pages = {705-707}, pmid = {24339616}, issn = {0972-2327}, abstract = {Klippel-Feil syndrome (KFS) is an unusual skeletal disorder characterized by congenital fusion of two or more cervical vertebrae which can be sporadic or familial. KFS emerges to be a failure of the normal segmentation and fusion of the mesodermal somites during 3(rd) and 8(th) weeks of embryonic development. The triad of low posterior hairline, short neck, and restricted neck motion is present only in 50% and often associated with scoliosis, spina bifida, Sprengel's deformity, cervical ribs, deafness, cleft palate, renal anomalies, congenital heart defects, and so on because of heterogeneous nature of the disease. The significance of KFS lies in the secondary effects produced on the nervous system, which usually presents with features of progressive cord and brain stem compression with relatively minor trauma. We here report two cases of KFS presented in association with amyotrophic lateral sclerosis. Only two such cases have been described in the literature in 1954 and 1975.}, } @article {pmid24334107, year = {2014}, author = {Costa, A and Foucart, A and Arnon, I and Aparici, M and Apesteguia, J}, title = {"Piensa" twice: on the foreign language effect in decision making.}, journal = {Cognition}, volume = {130}, number = {2}, pages = {236-254}, doi = {10.1016/j.cognition.2013.11.010}, pmid = {24334107}, issn = {1873-7838}, mesh = {Decision Making/*physiology ; Female ; Humans ; *Language ; Male ; Problem Solving ; Young Adult ; }, abstract = {In this article, we assess to what extent decision making is affected by the language in which a given problem is presented (native vs. foreign). In particular, we aim to ask whether the impact of various heuristic biases in decision making is diminished when the problems are presented in a foreign language. To this end, we report four main studies in which more than 700 participants were tested on different types of individual decision making problems. In the first study, we replicated Keysar et al.'s (2012) recent observation regarding the foreign language effect on framing effects related to loss aversion. In the second section, we assessed whether the foreign language effect is present in other types of framing problems that involve psychological accounting biases rather than gain/loss dichotomies. In the third section, we studied the foreign language effect in several key aspects of the theory of decision making under risk and uncertainty. In the fourth study, we assessed the presence of a foreign language effect in the cognitive reflection test, a test that includes logical problems that do not carry emotional connotations. The absence of such an effect in this test suggests that foreign language leads to a reduction of heuristic biases in decision making across a range of decision making situations and provide also some evidence about the boundaries of the phenomenon. We explore several potential factors that may underlie the foreign language effect in decision making.}, } @article {pmid24328352, year = {2014}, author = {Koegel, LK and Koegel, RL and Ashbaugh, K and Bradshaw, J}, title = {The importance of early identification and intervention for children with or at risk for autism spectrum disorders.}, journal = {International journal of speech-language pathology}, volume = {16}, number = {1}, pages = {50-56}, doi = {10.3109/17549507.2013.861511}, pmid = {24328352}, issn = {1754-9515}, mesh = {Humans ; }, abstract = {There has been a dramatic rise in the number of children being diagnosed with autism spectrum disorders (ASD), which has led to increased attention paid to assessment and intervention issues. This manuscript agrees with Camarata (2014) that the evidence base for early assessment and intervention should be expanded. However, it disagrees with Warren et al.'s (2011) assumption that there are not empirically validated early interventions. Reliable diagnosis has been documented during infancy and toddlerhood, and evidence suggests that the earlier the onset of intervention, the greater likelihood of an improved developmental trajectory. It is argued that early intervention is more cost and time efficient than a "wait and see" approach. With regard to published studies, the large amount of heterogeneity in the ASD population supports the use of rigorous single case experimental design research. It is an error to limit empirical evidence for treatments to only randomized clinical trials, which have the weakness of masking individual differences. Single case experimental designs examine the effects of intervention beyond typical maturation by allowing for clear estimations of developmental trajectories prior to the onset of intervention, followed by evaluation of the impact of the intervention. This commentary discusses the short- and long-term benefits of early diagnosis and intervention.}, } @article {pmid24328005, year = {2013}, author = {Kudo, Y}, title = {The role of placental indoleamine 2,3-dioxygenase in human pregnancy.}, journal = {Obstetrics & gynecology science}, volume = {56}, number = {4}, pages = {209-216}, pmid = {24328005}, issn = {2287-8572}, abstract = {Munn et al. made a scientific observation of major biological importance. For the first time they showed that in the mammal the fetus does survive an immune attack mounted by the mother, and that the mechanism responsible for the survival depends on the fetus and placenta 'actively' defending itself from attack by maternal T cells by means of an enzyme indoleamine 2,3-dioxygenase (EC 1.13.11.42) dependent localised depletion of L-tryptophan. These findings raise critical questions for disease and its prevention during human pregnancy. Specifically, the role of this mechanism (discovered in mouse) in the human, and the extent to which defective activation of this process is responsible for major clinical diseases are unknown. Therefore some key facts about this enzyme expressed in the human placenta have been studied in order to test whether Munn et al.'s findings in mouse are met for human pregnancy. This short review attempts to describe our experimental work on human placental indoleamine 2,3-dioxygenase.}, } @article {pmid24326181, year = {2013}, author = {Moshfeghi, M and Rahimi, H and Rahimi, H and Nouri, M and Bagheban, AA}, title = {Predicting mandibular growth increment on the basis of cervical vertebral dimensions in Iranian girls.}, journal = {Progress in orthodontics}, volume = {14}, number = {1}, pages = {3}, pmid = {24326181}, issn = {2196-1042}, mesh = {Cephalometry/methods/statistics & numerical data ; Cervical Vertebrae/*anatomy & histology ; Child ; Female ; Follow-Up Studies ; Forecasting ; Humans ; Iran ; Longitudinal Studies ; Mandible/anatomy & histology/*growth & development ; Regression Analysis ; }, abstract = {BACKGROUND: The purpose of this longitudinal study was to establish an equation to predict incremental mandibular length on the basis of the analysis of the cervical vertebrae on a single cephalometric radiograph and to compare the predictive accuracy with the method by Mito et al.

METHODS: Data consist of a group of 33 Iranian girls, 9 to 11 years old with two lateral cephalometric radiographs taken at a 24-month interval. For each individual, on the lateral cephalometric radiographs, points and lines for the description of the morphologic characteristics of the third and fourth cervical vertebral bodies were traced and measured. The real mandibular length increment (MLI) in this period was determined by the difference between the second (24 months) and first (baseline) radiographs: MLI=Ar-Pog (second)-Ar-Pog (first). An equation was determined to calculate mandibular length increments on the basis of the measurements in the third and fourth cervical vertebral bodies. The predictive accuracy was assessed using multiple regression analysis.

RESULTS: The adjusted R2 for this equation was 54.9% which is a reliable value for evaluating prediction accuracy .The average error between the predicted increment and the actual increment was 0.149 mm for our method and 5.87 mm for the method by Mito et al.

DISCUSSION: There are two items that contributed to easier and better prediction accuracy in our equation: (1) higher R2 and (2) fewer independent variables. In our subjects, the prediction accuracy was lower when using Mito et al.'s method, which could be due to genetic and environmental factors and selected age range.

CONCLUSION: These results indicate that cervical vertebral measurements, obtained in lateral cephalograms, are able to predict properly the mandibular growth potential.}, } @article {pmid24323640, year = {2014}, author = {Duboc, O and Dignac, MF and Djukic, I and Zehetner, F and Gerzabek, MH and Rumpel, C}, title = {Lignin decomposition along an Alpine elevation gradient in relation to physicochemical and soil microbial parameters.}, journal = {Global change biology}, volume = {20}, number = {7}, pages = {2272-2285}, doi = {10.1111/gcb.12497}, pmid = {24323640}, issn = {1365-2486}, mesh = {Altitude ; Carbon/*metabolism ; Carbon Isotopes/analysis ; Climate Change ; Copper/metabolism ; Lignin/*metabolism ; Phenols/metabolism ; Seasons ; Soil/*chemistry ; *Soil Microbiology ; Temperature ; Zea mays/*chemistry ; }, abstract = {Lignin is an aromatic plant compound that decomposes more slowly than other organic matter compounds; however, it was recently shown that lignin could decompose as fast as litter bulk carbon in minerals soils. In alpine Histosols, where organic matter dynamics is largely unaffected by mineral constituents, lignin may be an important part of soil organic matter (SOM). These soils are expected to experience alterations in temperature and/or physicochemical parameters as a result of global climate change. The effect of these changes on lignin dynamics remains to be examined and the importance of lignin as SOM compound in these soils evaluated. Here, we investigated the decomposition of individual lignin phenols of maize litter incubated for 2 years in-situ in Histosols on an Alpine elevation gradient (900, 1300, and 1900 m above sea level); to this end, we used the cupric oxide oxidation method and determined the phenols' (13) C signature. Maize lignin decomposed faster than bulk maize carbon in the first year (86 vs. 78% decomposed); however, after the second year, lignin and bulk C decomposition did not differ significantly. Lignin mass loss did not correlate with soil temperature after the first year, and even correlated negatively at the end of the second year. Lignin mass loss also correlated negatively with the remaining maize N at the end of the second year, and we interpreted this result as a possible negative influence of nitrogen on lignin degradation, although other factors (notably the depletion of easily degradable carbon sources) may also have played a role at this stage of decomposition. Microbial community composition did not correlate with lignin mass loss, but it did so with the lignin degradation indicators (Ac/Al)s and S/V after 2 years of decomposition. Progressing substrate decomposition toward the final stages thus appears to be linked with microbial community differentiation.}, } @article {pmid24304805, year = {2013}, author = {Zayas, V and Günaydin, G and Pandey, G}, title = {Persistence: what does research on self-regulation and delay of gratification have to say?.}, journal = {The Behavioral and brain sciences}, volume = {36}, number = {6}, pages = {706-7; discussion 707-26}, doi = {10.1017/S0140525X13001490}, pmid = {24304805}, issn = {1469-1825}, mesh = {Humans ; Mental Fatigue/*psychology ; *Models, Psychological ; }, abstract = {Despite the simplicity of Kurzban et al.'s framework, we argue that important information is lost in their simplification. We discuss research on delay of gratification and self-regulation that identifies key situational and psychological factors affecting how people represent rewards and costs. These factors affect the expected utilities of behavioral options and thus dramatically influence whether individuals persist on a difficult task.}, } @article {pmid24304803, year = {2013}, author = {Westbrook, JA and Braver, TS}, title = {The economics of cognitive effort.}, journal = {The Behavioral and brain sciences}, volume = {36}, number = {6}, pages = {704-5; discussion 707-26}, doi = {10.1017/S0140525X13001179}, pmid = {24304803}, issn = {1469-1825}, mesh = {Humans ; Mental Fatigue/*psychology ; *Models, Psychological ; }, abstract = {If cognitive effort indexes opportunity costs, it should be investigated like other cost factors including risk and delay. We discuss recent methodological advances in behavioral economics and neuroeconomics, highlighting our own work in measuring the subjective (economic) value of cognitive effort. We discuss the implications of Kurzban et al.'s proposal and how some of its predictions may be untestable without behavioral economic formalisms.}, } @article {pmid24304802, year = {2013}, author = {Tops, M and Boksem, MA and Koole, SL}, title = {Subjective effort derives from a neurological monitor of performance costs and physiological resources.}, journal = {The Behavioral and brain sciences}, volume = {36}, number = {6}, pages = {703-4; discussion 707-26}, doi = {10.1017/S0140525X13001167}, pmid = {24304802}, issn = {1469-1825}, mesh = {Humans ; Mental Fatigue/*psychology ; *Models, Psychological ; }, abstract = {Kurzban et al.'s expectancy-value mechanism of effort allocation seems relevant in situations when familiar tasks are initiated. However, we think additional mechanisms are important when people continue with a task for a prolonged time. These mechanisms, which are particularly relevant for performance of novel or urgent tasks, involve neural systems that track performance costs and resources.}, } @article {pmid24304800, year = {2013}, author = {Nicolle, A and Riggs, K}, title = {The costs of giving up: action versus inaction asymmetries in regret.}, journal = {The Behavioral and brain sciences}, volume = {36}, number = {6}, pages = {702; discussion 707-26}, doi = {10.1017/S0140525X13001143}, pmid = {24304800}, issn = {1469-1825}, mesh = {Humans ; Mental Fatigue/*psychology ; *Models, Psychological ; }, abstract = {Kurzban et al.'s opportunity cost model of mental effort relies heavily on counterfactual thinking. We suggest that a closer inspection of the role of counterfactual emotions, and particularly of action/inaction asymmetries in anticipated regret, may be important in understanding the role of opportunity costs in decisions to persist with a current task.}, } @article {pmid24304794, year = {2013}, author = {Iran-Nejad, A and Zengaro, SA}, title = {Opportunity prioritization, biofunctional simultaneity, and psychological mutual exclusion.}, journal = {The Behavioral and brain sciences}, volume = {36}, number = {6}, pages = {696-7; discussion 707-26}, doi = {10.1017/S0140525X13001088}, pmid = {24304794}, issn = {1469-1825}, mesh = {Humans ; Mental Fatigue/*psychology ; *Models, Psychological ; }, abstract = {We argue that prioritization, simultaneity, and mutual exclusion are mind-body integration functions that can't be addressed meaningfully at the psychological (computational) level alone. We describe the outlook for an integration between Kurzban et al.'s profound discussion of opportunity cost/benefit prioritization and decades of related development in biofunctional science.}, } @article {pmid24304790, year = {2013}, author = {Hofmann, W and Kotabe, H}, title = {On treating effort as a dynamically varying cost input.}, journal = {The Behavioral and brain sciences}, volume = {36}, number = {6}, pages = {692-3; discussion 707-26}, doi = {10.1017/S0140525X13001040}, pmid = {24304790}, issn = {1469-1825}, mesh = {Humans ; Mental Fatigue/*psychology ; *Models, Psychological ; }, abstract = {Kurzban et al.'s framework may be extended in fruitful ways by treating effort also as a cost input that affects the utility computation of a given option (rather than only as the output of a utility comparison between options). The weight people assign to effort as a cost may vary dynamically as a function of situational and dispositional factors.}, } @article {pmid24304789, year = {2013}, author = {Hillman, KL and Bilkey, DK}, title = {Persisting through subjective effort: a key role for the anterior cingulate cortex?.}, journal = {The Behavioral and brain sciences}, volume = {36}, number = {6}, pages = {691-2; discussion 707-26}, doi = {10.1017/S0140525X13001039}, pmid = {24304789}, issn = {1469-1825}, mesh = {Humans ; Mental Fatigue/*psychology ; *Models, Psychological ; }, abstract = {One shortcoming of Kurzban et al.'s model is that it is not clear how animals persist through subjectively effortful tasks, particularly over a long time course. We suggest that the anterior cingulate cortex plays a critical role by encoding the utility of an action, and signalling where efforts should be best directed based on previous and prospected experience.}, } @article {pmid24304786, year = {2013}, author = {Harrison, JM and McKay, R}, title = {Give me strength or give me a reason: self-control, religion, and the currency of reputation.}, journal = {The Behavioral and brain sciences}, volume = {36}, number = {6}, pages = {688-9; discussion 707-26}, doi = {10.1017/S0140525X13001003}, pmid = {24304786}, issn = {1469-1825}, mesh = {Humans ; Mental Fatigue/*psychology ; *Models, Psychological ; }, abstract = {We show that Kurzban et al.'s approach illuminates the relationship between religion and self-control. Whereas resource-depletion theorists suggest religion replenishes self-control resources ("strength"), we submit that religious cues make people feel observed, giving them "reason" to persevere, and we describe an experiment that supports our interpretation. Finally, we question the claim that subjective fatigue is a signal to redeploy resources.}, } @article {pmid24304785, year = {2013}, author = {Hagger, MS}, title = {The opportunity cost model: automaticity, individual differences, and self-control resources.}, journal = {The Behavioral and brain sciences}, volume = {36}, number = {6}, pages = {687-8; discussion 707-26}, doi = {10.1017/S0140525X1300099X}, pmid = {24304785}, issn = {1469-1825}, mesh = {Humans ; Mental Fatigue/*psychology ; *Models, Psychological ; }, abstract = {I contend that Kurzban et al.'s model is silent on three issues. First, the extent to which opportunity-cost computations are automatic or deliberative is unclear. Second, the role of individual differences in biasing opportunity-cost computations needs elucidating. Third, in the absence of "next-best" tasks, task persistence will be indefinite, which seems unfeasible, so perhaps integration with a limited-resource account is necessary.}, } @article {pmid24304784, year = {2013}, author = {Gendolla, GH and Richter, M}, title = {Opportunity cost calculations only determine justified effort--or, what happened to the resource conservation principle?.}, journal = {The Behavioral and brain sciences}, volume = {36}, number = {6}, pages = {686-7; discussion 707-26}, doi = {10.1017/S0140525X13000988}, pmid = {24304784}, issn = {1469-1825}, mesh = {Humans ; Mental Fatigue/*psychology ; *Models, Psychological ; }, abstract = {We welcome the development of a new model on effort and performance and the critique on existing resource-based models. However, considering the vast evidence for the significant impact of experienced task demand on resource allocation, we conclude that Kurzban et al.'s opportunity cost model is only valid for one performance condition: if task demand is unknown or unspecified.}, } @article {pmid24304779, year = {2013}, author = {Brzezicka, A and Kamiński, J and Wróbel, A}, title = {Local resource depletion hypothesis as a mechanism for action selection in the brain.}, journal = {The Behavioral and brain sciences}, volume = {36}, number = {6}, pages = {682-3; discussion 707-26}, doi = {10.1017/S0140525X13000940}, pmid = {24304779}, issn = {1469-1825}, mesh = {Humans ; Mental Fatigue/*psychology ; *Models, Psychological ; }, abstract = {As a comment on Kurzban et al.'s opportunity cost model, we propose an alternative view of mental effort and the action selection mechanism in the brain. Our hypothesis utilizes local resource depletion within neuronal networks, which justifies from a neurophysiological perspective why mental fatigue diminishes after switching to a novel task and explains action selection by means of neural competition theory.}, } @article {pmid24304778, year = {2013}, author = {Bruyneel, SD and Dewitte, S}, title = {An addition to Kurzban et al.'s model: thoroughness of cost-benefit analyses depends on the executive tasks at hand.}, journal = {The Behavioral and brain sciences}, volume = {36}, number = {6}, pages = {681-2; discussion 707-26}, doi = {10.1017/S0140525X13000939}, pmid = {24304778}, issn = {1469-1825}, mesh = {Humans ; Mental Fatigue/*psychology ; *Models, Psychological ; }, abstract = {Though Kurzban et al.'s model explains a considerable set of empirical findings, it cannot accommodate other results without relying on extra assumptions. We offer an addition to the model, and suggest that cost-benefit analyses themselves depend on executive function, and therefore can be biased. The adapted model allows for explaining depletion effects, as well as their reversals, documented in the literature.}, } @article {pmid24300061, year = {2013}, author = {Swift, AU and Tate, RB}, title = {Themes from older men's lay definitions of successful aging as indicators of primary and secondary control beliefs over time: The Manitoba Follow-up Study.}, journal = {Journal of aging studies}, volume = {27}, number = {4}, pages = {410-418}, doi = {10.1016/j.jaging.2013.09.004}, pmid = {24300061}, issn = {1879-193X}, mesh = {Aged ; Aged, 80 and over ; Aging/*psychology ; *Attitude to Health ; Follow-Up Studies ; Humans ; Internal-External Control ; Male ; Men/*psychology ; Narration ; Perception ; Physical Fitness ; Time Factors ; }, abstract = {Constructs of control have theoretically been equated to successful aging in the psychology literature. Hence, we used themes from lay definitions of successful aging to quantify the prevalence of primary and secondary control beliefs over time. In doing so we hoped to shed new light upon the virtually uncharted area of older men's primary and secondary control beliefs over time. Using successful aging narratives spanning a 10-year timeframe from the Manitoba Follow-up Study cohort, we mapped themes from older men's lay definitions of successful aging onto Rothbaum, Weisz, and Snyder's (1982) constructs of primary and secondary control. We then examined the prevalence of the constructs of control over 10 years and found that some men emphasized primary control, some emphasized secondary control, and others emphasized both, prospectively. Counter to what had previously been theorized, many older men continued to emphasize primary control as important well into late life. As expected, secondary control became more important with age. Furthermore, among those men who endorsed both primary and secondary control, significantly more men switched emphasis from primary to secondary control beliefs as they aged. This finding supported Rothbaum et al.'s (1982) surmise that individuals could switch from one type of control to another, presumably as life circumstances dictated. Knowing which types of control beliefs older men emphasize as they age has theoretical and practical implications. Theoretically, it sheds new light on the under-researched area of control beliefs in older men. Practically, it is informative for anyone interested in enhancing older men's perceptions of control in very late life, particularly in the face of otherwise uncontrollable age-related decline and imminent demise.}, } @article {pmid24268462, year = {2014}, author = {Agostinelli, A and Giuliani, C and Burattini, L}, title = {Use of the dominant T wave to enhance reliability of T-wave offset identification.}, journal = {Journal of electrocardiology}, volume = {47}, number = {1}, pages = {98-105}, doi = {10.1016/j.jelectrocard.2013.09.007}, pmid = {24268462}, issn = {1532-8430}, mesh = {*Algorithms ; Diagnosis, Computer-Assisted/*methods ; Electrocardiography/*methods ; Female ; Humans ; Male ; Middle Aged ; Myocardial Infarction/*diagnosis ; Reproducibility of Results ; Sensitivity and Specificity ; }, abstract = {T-wave offset (Toff) identification may be jeopardized by the presence of a significant inter-method (IMV) and inter-lead (ILV) Toff variability. Thus, the aim of the present study was to investigate if the dominant T wave (DTW) may be used to enhance Toff-identification reliability. DTWs and 15-lead ECG T waves of 46 control healthy subjects (CHS) and 103 acute myocardial infarction patients (AMIP) were analyzed for Toff identification using Zhang et al.'s (M1) and Daskalov and Christov's (M2) methods. Results indicate that IMV is significantly reduced when identifying Toff from the DTW rather than from single ECG leads in both populations (CHS: 5ms vs. 5-15ms; AMIP: 10ms vs. 10-20ms). Moreover, when analyzing ILV, Toff was found to be equivalent (correlation=0.71-0.98; P<10(-14)) to the median Toff among leads, but required only one identification instead of 15. Thus, the DTW can be used to enhance Toff-identification reliability.}, } @article {pmid24260844, year = {2013}, author = {Bauman, JG}, title = {Depression in adolescents: review of a nursing research report.}, journal = {Kentucky nurse}, volume = {61}, number = {4}, pages = {4}, pmid = {24260844}, issn = {0742-8367}, mesh = {Depressive Disorder/*nursing/*psychology ; Female ; Humans ; Male ; Quality of Life/*psychology ; *Social Adjustment ; }, abstract = {The research findings from the McCann et al.'s (2012) study are important to evidence-based nursing practice (EBNP) as they highlight the need to improve mental health literacy for health care professionals, including nurses, so that nurses are more aware of the signs of depression, young people's experiences of depression, and how to respond appropriately to their needs (McCann et al., 2012, p. 339). The findings that government funding, along with knowledgeable health care professionals, improved community awareness, and support of young people with depression, played a vital role in strengthening young people's ability to counteract the stigma while promoting self-empowerment, indicate the need for the identification and implementation of EBNP interventions incorporating their finding. (McCann et al., 2012, p. 339). One suggestion for future research would be to develop EBNP interventions designed to promote a smooth transition from youth to adulthood in those with depression and to conduct a research study evaluating the effectiveness of interventions implemented.}, } @article {pmid24243138, year = {2014}, author = {LeBel, EP and Wilbur, CJ}, title = {Big secrets do not necessarily cause hills to appear steeper.}, journal = {Psychonomic bulletin & review}, volume = {21}, number = {3}, pages = {696-700}, pmid = {24243138}, issn = {1531-5320}, mesh = {Adolescent ; Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Research Design/*standards ; Space Perception/*physiology ; Young Adult ; }, abstract = {Slepian, Masicampo, Toosi, and Ambady (Journal of Experimental Psychology: General, 141, 619-624, 2012, Study 1) found that individuals recalling and writing about a big, meaningful secret judged a pictured hill as steeper than did those who recalled and wrote about a small, inconsequential secret (with estimates unrelated to physical effort unaffected). From an embodied cognition perspective, this result was interpreted as suggesting that important secrets weigh people down. Answering to mounting calls for the crucial need of independent direct replications of published findings to ensure the self-correcting nature of our science, we sought to corroborate Slepian et al.'s finding in two extremely high-powered, preregistered studies that were very faithful to all procedural and methodological details of the original study (i.e., same cover story, study title, manipulation, measures, item order, scale anchors, task instructions, sampling frame, population, and statistical analyses). In both samples, we were unsuccessful in replicating the target finding. Although Slepian et al. reported three other studies supporting the secret burdensomeness phenomenon, we advise that these three other findings need to be independently corroborated before the general phenomenon informs theory or health interventions.}, } @article {pmid24238842, year = {2014}, author = {Vaa, T}, title = {ADHD and relative risk of accidents in road traffic: a meta-analysis.}, journal = {Accident; analysis and prevention}, volume = {62}, number = {}, pages = {415-425}, doi = {10.1016/j.aap.2013.10.003}, pmid = {24238842}, issn = {1879-2057}, mesh = {Accidents, Traffic/*statistics & numerical data ; Attention Deficit Disorder with Hyperactivity/*epidemiology ; Attention Deficit and Disruptive Behavior Disorders/epidemiology ; Automobile Driving/*statistics & numerical data ; Comorbidity ; Conduct Disorder/epidemiology ; Female ; Humans ; Male ; Risk ; }, abstract = {The present meta-analysis is based on 16 studies comprising 32 results. These studies provide sufficient data to estimate relative accident risks of drivers with ADHD. The overall estimate of relative risk for drivers with ADHD is 1.36 (95% CI: 1.18; 1.57) without control for exposure, 1.29 (1.12; 1.49) when correcting for publication bias, and 1.23 (1.04; 1.46) when controlling for exposure. A relative risk (RR) of 1.23 is exactly the same as found for drivers with cardiovascular diseases. The long-lasting assertion that "ADHD-drivers have an almost fourfold risk of accident compared to non-ADHD-drivers", which originated from Barkley et al.'s study of 1993, is rebutted. That estimate was associated with comorbid Oppositional Defiant Disorder (ODD) and/or Conduct Disorder (CD), not with ADHD, but the assertion has incorrectly been maintained for two decades. The present study provides some support for the hypothesis that the relative accident risk of ADHD-drivers with comorbid ODD, CD and/or other conduct problems, is higher than that of ADHD-drivers without these comorbidities. The estimated RRs were 1.86 (1.27; 2.75) in a sample of ADHD-drivers in which a majority had comorbid ODD and/or CD compared to 1.31 (0.96; 1.81) in a sample of ADHD-drivers with no comorbidity. Given that ADHD-drivers most often seem to drive more than controls, and the fact that a majority of the present studies lack information about exposure, it seems more probable that the true RR is lower rather than higher than 1.23. Also the assertion that ADHD-drivers violate traffic laws more often than other drivers should be modified: ADHD-drivers do have more speeding violations, but no more drunk or reckless driving citations than drivers without ADHD. All accident studies included in the meta-analysis fail to acknowledge the distinction between deliberate violations and driving errors. The former are known to be associated with accidents, the latter are not. A hypothesis that ADHD-drivers speed more frequently than controls because it stimulates attention and reaction time is suggested.}, } @article {pmid24224173, year = {2013}, author = {Witoński, D and Kęska, R and Synder, M and Sibiński, M}, title = {An isolated medial patellofemoral ligament reconstruction with patellar tendon autograft.}, journal = {BioMed research international}, volume = {2013}, number = {}, pages = {637678}, pmid = {24224173}, issn = {2314-6141}, mesh = {Adolescent ; Adult ; Female ; Humans ; Knee Joint/pathology/*surgery ; Ligaments ; Male ; Patellar Ligament/pathology/*surgery ; *Plastic Surgery Procedures ; Tendons/*surgery ; Transplantation, Autologous ; Treatment Outcome ; }, abstract = {The aim of the study was to evaluate the results of the medial patellofemoral ligament reconstruction with a medial strip of patellar tendon autograft after a minimum 2-year followup. Ten patients (10 knees) were operated on by one surgeon, according to the modified technique, described by Camanho, without any bone plug at free graft end. The mean age of the patients was 27.2 years (ranging from 18 to 42 years). The mean follow-up period was 3 years and 7 months. All patients were reviewed prospectively. At the last follow-up visit, all the patients demonstrated a significant improvement in terms of patellofemoral joint stability, all aspects of the KOOS questionnaire, and Kujala et al.'s score (59.7 points preoperatively and 84.4 points at the last followup). No patient revealed recurrent dislocation. The SF-36 score revealed a significant improvement in bodily pain, general health, physical role functioning, social role functioning, and physical functioning domains. The described MPFL reconstruction with the use of the medial 1/3rd of patella tendon is an effective procedure that gives satisfactorily patellofemoral joint functions, improves the quality of life, and provides much pain relief. It is relatively simple, surgically not extensive, and economically cost-effective procedure.}, } @article {pmid24223257, year = {2013}, author = {Hardij, J and Cecchet, F and Berquand, A and Gheldof, D and Chatelain, C and Mullier, F and Chatelain, B and Dogné, JM}, title = {Characterisation of tissue factor-bearing extracellular vesicles with AFM: comparison of air-tapping-mode AFM and liquid Peak Force AFM.}, journal = {Journal of extracellular vesicles}, volume = {2}, number = {}, pages = {}, pmid = {24223257}, issn = {2001-3078}, abstract = {INTRODUCTION: Extracellular vesicles (EVs) are shed from cells and carry markers of the parent cells. Vesicles derived from cancer cells reach the bloodstream and locally influence important physiological processes. It has been previously shown that procoagulant vesicles are circulating in patients' fluids. These EVs are therefore considered as promising biomarkers for the thrombotic risk. Because of their small size, classical methods such as flow cytometry suffer from limitation for their characterisation. Atomic force microscopy (AFM) has been proposed as a promising complementary method for the characterisation of EVs.

OBJECTIVES: THE OBJECTIVES OF THIS STUDY ARE: (a) to develop and validate AFM with specific antibodies (anti-TF) and (b) to compare air and liquid modes for EVs' size and number determination as potential biomarkers of the prothrombotic risk.

METHODS: AFM multimode nanoscope III was used for air tapping mode (TM). AFM catalyst was used for liquid Peak Force Tapping (PFT) mode. Vesicles are generated according to Davila et al.'s protocol. Substrates are coated with various concentrations of antibodies, thanks to ethanolamine and glutaraldehyde.

RESULTS: Vesicles were immobilised on antibody-coated surfaces to select tissue factor (TF)-positive vesicles. The size range of vesicles observed in liquid PFT mode is 6-10 times higher than in air mode. This corresponds to the data found in the literature.

CONCLUSION: We recommend liquid PFT mode to analyse vesicles on 5 µg/ml antibody-coated substrates.}, } @article {pmid24214438, year = {2013}, author = {Armstrong, N}, title = {Aerobic fitness and physical activity in children.}, journal = {Pediatric exercise science}, volume = {25}, number = {4}, pages = {548-560}, doi = {10.1123/pes.25.4.548}, pmid = {24214438}, issn = {1543-2920}, mesh = {Accelerometry ; Child ; Child Development ; Developed Countries ; Exercise Test ; *Exercise Tolerance ; Humans ; Motor Activity/*physiology ; *Oxygen Consumption ; *Physical Fitness ; Surveys and Questionnaires ; }, abstract = {In Volume 1 of Pediatric Exercise Science (PES), a paper by Fenster et al. (25) investigated the relationship between peak oxygen uptake (peak VO2) and physical activity (PA) in 6- to 8-year-old children. They used both questionnaires and large-scale integrated activity monitors (LSIs) to estimate daily PA and determined peak VO2 using an incremental treadmill test to volitional exhaustion. They concluded that peak VO2 correlated well with PA as measured by LSIs but commented that questionnaire data were only weakly and nonsignificantly associated with LSI and peak VO2 data. Peak VO2 and PA are the most researched and reported variables in the 25-year history of PES. Yet, the assessment and interpretation of young people's aerobic fitness and PA remain problematic and any meaningful relationship between them during childhood and adolescence is shrouded with controversy. The present paper uses Fenster et al.'s (25) report as an indicator of where we were 25 years ago, outlines how far we have advanced since then, and suggests future directions of research in the study of aerobic fitness and PA. In the first volume of PES, Fenster, Freedson, Washburn, and Ellison (25) investigated the relationship between 6- to 8-year-old children's peak oxygen uptake (peak VO2) and physical activity (PA). Five boys and 13 girls participated in the study and their data were pooled for analysis. Peak VO2 was determined during an incremental treadmill test to voluntary exhaustion and PA was estimated using both questionnaires and large-scale integrated activity monitors (LSIs). On the basis of a significant interclass correlation coefficient of r = .59 between peak VO2 and the log of LSI average counts per hour Fenster et al. (25) concluded that "aerobic capacity, as measured by peak VO2 correlated well with physical activity as measured by LSI" (p.134). They also commented that questionnaire data were only weakly and nonsignificantly associated with LSI and peak VO2 data. Young people's peak VO2 and PA are the most researched and reported variables in the 25-year history of PES and yet the assessment and interpretation of peak VO2 and PA and any meaningful relationship between them during growth and maturation are still shrouded with controversy. The present paper uses Fenster et al.'s (25) work as an indicator of our understanding of young people's peak VO2 and PA in 1989, briefly reviews what we know in 2013, and suggests future directions of research.}, } @article {pmid24211919, year = {2014}, author = {Zhou, L and Zhou, L and Zhang, S and Zhen, X and Yu, H and Zhang, G and Wang, R}, title = {Validation of an improved 'diffeomorphic demons' algorithm for deformable image registration in image-guided radiation therapy.}, journal = {Bio-medical materials and engineering}, volume = {24}, number = {1}, pages = {373-382}, doi = {10.3233/BME-130821}, pmid = {24211919}, issn = {1878-3619}, mesh = {*Algorithms ; Contrast Media/chemistry ; Humans ; Image Processing, Computer-Assisted/*methods ; Models, Theoretical ; Neoplasms/pathology ; Normal Distribution ; Phantoms, Imaging ; Radiotherapy ; *Radiotherapy Planning, Computer-Assisted ; Regression Analysis ; Software ; Tomography, X-Ray Computed ; }, abstract = {Deformable image registration (DIR) was widely used in radiation therapy, such as in automatic contour generation, dose accumulation, tumor growth or regression analysis. To achieve higher registration accuracy and faster convergence, an improved 'diffeomorphic demons' registration algorithm was proposed and validated. Based on Brox et al.'s gradient constancy assumption and Malis's efficient second-order minimization (ESM) algorithm, a grey value gradient similarity term and a transformation error term were added into the demons energy function, and a formula was derived to calculate the update of transformation field. The limited Broyden-Fletcher-Goldfarb-Shanno (L-BFGS) algorithm was used to optimize the energy function so that the iteration number could be determined automatically. The proposed algorithm was validated using mathematically deformed images and physically deformed phantom images. Compared with the original 'diffeomorphic demons' algorithm, the registration method proposed achieve a higher precision and a faster convergence speed. Due to the influence of different scanning conditions in fractionated radiation, the density range of the treatment image and the planning image may be different. In such a case, the improved demons algorithm can achieve faster and more accurate radiotherapy.}, } @article {pmid24204582, year = {2013}, author = {Wang, Y and Jiang, D and Zhuang, D and Huang, Y and Wang, W and Yu, X}, title = {Effective key parameter determination for an automatic approach to land cover classification based on multispectral remote sensing imagery.}, journal = {PloS one}, volume = {8}, number = {10}, pages = {e75852}, pmid = {24204582}, issn = {1932-6203}, mesh = {China ; *Geographic Mapping ; Humans ; *Satellite Imagery ; }, abstract = {The classification of land cover based on satellite data is important for many areas of scientific research. Unfortunately, some traditional land cover classification methods (e.g. known as supervised classification) are very labor-intensive and subjective because of the required human involvement. Jiang et al. proposed a simple but robust method for land cover classification using a prior classification map and a current multispectral remote sensing image. This new method has proven to be a suitable classification method; however, its drawback is that it is a semi-automatic method because the key parameters cannot be selected automatically. In this study, we propose an approach in which the two key parameters are chosen automatically. The proposed method consists primarily of the following three interdependent parts: the selection procedure for the pure-pixel training-sample dataset, the method to determine the key parameters, and the optimal combination model. In this study, the proposed approach employs both overall accuracy and their Kappa Coefficients (KC), and Time-Consumings (TC, unit: second) in order to select the two key parameters automatically instead of using a test-decision, which avoids subjective bias. A case study of Weichang District of Hebei Province, China, using Landsat-5/TM data of 2010 with 30 m spatial resolution and prior classification map of 2005 recognised as relatively precise data, was conducted to test the performance of this method. The experimental results show that the methodology determining the key parameters uses the portfolio optimisation model and increases the degree of automation of Jiang et al.'s classification method, which may have a wide scope of scientific application.}, } @article {pmid24188419, year = {2013}, author = {Batchelder, WH and Alexander, GE}, title = {Discrete-state models: comment on Pazzaglia, Dube, and Rotello (2013).}, journal = {Psychological bulletin}, volume = {139}, number = {6}, pages = {1204-1212}, doi = {10.1037/a0033894}, pmid = {24188419}, issn = {1939-1455}, mesh = {Humans ; Memory/*physiology ; Mental Processes/*physiology ; *Models, Psychological ; Recognition, Psychology/*physiology ; Signal Detection, Psychological/*physiology ; }, abstract = {Pazzaglia, Dube, and Rotello (2013) have provided a lengthy critique of threshold and continuous models of recognition memory. Although the early pages of their article focus mostly on the problems they see with 3 vintage threshold models compared with models from signal detection theory (SDT), it becomes clear rather quickly that Pazzaglia et al. are concerned more generally with problems they see with multinomial processing tree (MPT) models. First, we focus on Pazzaglia et al.'s discussion of the evidence concerning receiver operating characteristics (ROCs) in simple recognition memory, then we consider problems they raise with a subclass of MPT models for more complex recognition memory paradigms, and finally we discuss the difference between scientific models and measurement models in the context of MPT and SDT models in general. We argue that Pazzaglia et al. have not adequately considered the evidence relevant to the viability of the simple threshold models and that they have not adequately represented the issues concerning validating a cognitive measurement model. We further argue that selective influence studies and model flexibility studies are as important as studies showing that a model can fit behavioral data. In particular, we note that despite over a half century of effort, no generally accepted scientific theory of recognition memory has emerged and that it is unlikely to ever emerge with studies using standard behavioral measures. Instead, we assert that useful measurement models of both the SDT and the MPT type have been and should continue to be developed.}, } @article {pmid24180293, year = {2013}, author = {Petrak, F and Herpertz, S and Stridde, E and Pfützner, A}, title = {Reply to "comments on Petrak et al.'s 'psychological insulin resistance in type 2 diabetes patients regarding oral antidiabetes treatment, subcutaneous insulin injections, or inhaled insulin': considerations for language and communication".}, journal = {Diabetes technology & therapeutics}, volume = {15}, number = {12}, pages = {1055-1056}, doi = {10.1089/dia.2013.0307}, pmid = {24180293}, issn = {1557-8593}, mesh = {Diabetes Mellitus, Type 2/*drug therapy ; Female ; Humans ; Hypoglycemia/*prevention & control ; Hypoglycemic Agents/*administration & dosage ; Insulin/*administration & dosage ; *Insulin Resistance ; Male ; Psychophysiologic Disorders/*drug therapy ; }, } @article {pmid24177715, year = {2014}, author = {Chiang, JH and Lin, CH}, title = {NCS: incorporating positioning data to quantify nucleosome stability in yeast.}, journal = {Bioinformatics (Oxford, England)}, volume = {30}, number = {6}, pages = {761-767}, doi = {10.1093/bioinformatics/btt621}, pmid = {24177715}, issn = {1367-4811}, mesh = {DNA, Fungal/genetics ; High-Throughput Nucleotide Sequencing ; Nucleosomes/*genetics ; Poly A/genetics ; Poly T/genetics ; Saccharomyces cerevisiae/*genetics/metabolism ; }, abstract = {MOTIVATION: With the spreading technique of mass sequencing, nucleosome positions and scores for their intensity have become available through several previous studies in yeast, but relatively few studies have specifically aimed to determine the score of nucleosome stability. Based on mass sequencing data, we proposed a nucleosome center score (NCS) for quantifying nucleosome stability by measuring shifts of the nucleosome center, and then mapping NCS scores to nucleosome positions in Brogaard et al.'s study.

RESULTS: We demonstrated the efficiency of NCS by known preference of A/T-based tracts for nucleosome formation, and showed that central nucleosomal DNA is more sensitive to A/T-based tracts than outer regions, which corresponds to the central histone tetramer-dominated region. We also found significant flanking preference around nucleosomal DNA for A/T-based dinucleotides, suggesting that neighboring sequences could affect nucleosome stability. Finally, the difference between results of NCS and Brogaard et al.'s scores was addressed and discussed.

CONTACTS: jchiang@mail.ncku.edu.tw

SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.}, } @article {pmid24171382, year = {2013}, author = {Holmes-Truscott, E and Speight, J}, title = {Comments on Petrak et al.'s "psychological insulin resistance in type 2 diabetes patients regarding oral antidiabetes treatment, subcutaneous insulin injections, or inhaled insulin": considerations for language and communication.}, journal = {Diabetes technology & therapeutics}, volume = {15}, number = {12}, pages = {1053-1054}, doi = {10.1089/dia.2013.0273}, pmid = {24171382}, issn = {1557-8593}, mesh = {Diabetes Mellitus, Type 2/*drug therapy ; Female ; Humans ; Hypoglycemia/*prevention & control ; Hypoglycemic Agents/*administration & dosage ; Insulin/*administration & dosage ; *Insulin Resistance ; Male ; Psychophysiologic Disorders/*drug therapy ; }, } @article {pmid24150875, year = {2014}, author = {Caulkins, JP}, title = {Commentary on Crowley et al.'s research priorities for economic analysis of prevention.}, journal = {Prevention science : the official journal of the Society for Prevention Research}, volume = {15}, number = {6}, pages = {799-802}, pmid = {24150875}, issn = {1573-6695}, mesh = {*Biomedical Research ; *Cost-Benefit Analysis ; Humans ; Preventive Medicine/*economics ; }, abstract = {Economic theory provides a textbook ideal for how to conduct efficiency analysis that determines optimal resource allocation. The real world is not, however, an ideal place. This article suggests that common sense should be allowed to temper zealous commitment to textbook ideals. The spirit and the process of economic evaluation may be as important as the "final answer" expressed as a summary statistic.}, } @article {pmid24146334, year = {2013}, author = {Wen, F}, title = {A robust uniqueness-and-anonymity-preserving remote user authentication scheme for connected health care.}, journal = {Journal of medical systems}, volume = {37}, number = {6}, pages = {9980}, pmid = {24146334}, issn = {1573-689X}, mesh = {Algorithms ; Computer Security/*instrumentation ; *Health Information Exchange ; *Health Services Administration ; Humans ; Information Systems/*instrumentation ; }, abstract = {User authentication plays an important role to protect resources or services from being accessed by unauthorized users. In a recent paper, Das et al. proposed a secure and efficient uniqueness-and-anonymity-preserving remote user authentication scheme for connected health care. This scheme uses three factors, e.g. biometrics, password, and smart card, to protect the security. It protects user privacy and is believed to have many abilities to resist a range of network attacks, even if the secret information stored in the smart card is compromised. In this paper, we analyze the security of Das et al.'s scheme, and show that the scheme is in fact insecure against the replay attack, user impersonation attacks and off-line guessing attacks. Then, we also propose a robust uniqueness-and-anonymity-preserving remote user authentication scheme for connected health care. Compared with the existing schemes, our protocol uses a different user authentication mechanism to resist replay attack. We show that our proposed scheme can provide stronger security than previous protocols. Furthermore, we demonstrate the validity of the proposed scheme through the BAN (Burrows, Abadi, and Needham) logic.}, } @article {pmid24140253, year = {2013}, author = {Romero-Martínez, A and Lila, M and Williams, RK and González-Bono, E and Moya-Albiol, L}, title = {Skin conductance rises in preparation and recovery to psychosocial stress and its relationship with impulsivity and testosterone in intimate partner violence perpetrators.}, journal = {International journal of psychophysiology : official journal of the International Organization of Psychophysiology}, volume = {90}, number = {3}, pages = {329-333}, doi = {10.1016/j.ijpsycho.2013.10.003}, pmid = {24140253}, issn = {1872-7697}, mesh = {Adult ; Enzyme-Linked Immunosorbent Assay ; Galvanic Skin Response/*physiology ; Humans ; Impulsive Behavior ; *Interpersonal Relations ; Male ; Middle Aged ; Prisoners/*psychology ; Statistics, Nonparametric ; Stress, Psychological/*physiopathology ; Testosterone/*metabolism ; Violence/*psychology ; }, abstract = {Intimate partner violence (IPV) perpetrators were categorized into 2 groups using Gottman et al.'s (1995) typology depending on their skin conductance (SC) reactivity to stress. Overall, type I perpetrators tend to show autonomic underarousal, whereas type II perpetrators present a preparatory hyperreactivity to confront stress. Moreover, impulsivity traits and testosterone (T) levels may modulate SC responses to increase the risk of proneness to violence. In this study, SC response to stress was assessed by comparing IPV perpetrators with non-violent controls while performing a modified version of the Trier Social Stress Test (TSST). Subjects with a history of IPV demonstrated higher non-specific SC responses during the recovery period than the non-violent controls. Nonetheless, there were no differences between groups in the case of mean SC levels. Furthermore, impulsivity and baseline T levels were associated with higher SC level reactivity during a preparation period only in IPV perpetrators, with both relationships being mediated by anger expression. Our results confirm that the IPV perpetrators correspond physiologically to type II and support the validity of SC as a diagnostic indicator for IPV classification. Our findings contribute to the development of effective treatment and prevention programs that could benefit from the use of biological indicators for analyzing the risk of recidivism in IPV perpetrators.}, } @article {pmid24135614, year = {2013}, author = {Godager, G and Wiesen, D}, title = {Profit or patients' health benefit? Exploring the heterogeneity in physician altruism.}, journal = {Journal of health economics}, volume = {32}, number = {6}, pages = {1105-1116}, doi = {10.1016/j.jhealeco.2013.08.008}, pmid = {24135614}, issn = {1879-1646}, mesh = {*Altruism ; Choice Behavior ; Confidence Intervals ; Humans ; Logistic Models ; *Physician-Patient Relations ; Physicians/*economics ; Practice Patterns, Physicians' ; Reimbursement, Incentive/economics ; Students, Medical/psychology ; }, abstract = {This paper investigates physician altruism toward patients' health benefit using behavioral data from Hennig-Schmidt et al.'s (2011) laboratory experiment. In the experiment, medical students in the role of physicians decide on the provision of medical services. The experimental setup allows us to identify the influence of profits and patients' health benefit on the choice of medical treatment. We estimate physician altruism, the weight individuals attach to patients' health benefit, by fitting mixed logit and multinomial logit regression models to the experimental data. Estimation results provide evidence for physician altruism. We find, however, substantial variation in the degree of physician altruism. We also discuss some implications of our results for the design of physician payment schemes in the light of the theoretical literature.}, } @article {pmid24134302, year = {2014}, author = {Strand, A and Parkkinen, VP}, title = {Causal knowledge in evidence-based medicine. In reply to Kerry et al.'s causation and evidence-based practice: an ontological review.}, journal = {Journal of evaluation in clinical practice}, volume = {20}, number = {6}, pages = {981-984}, doi = {10.1111/jep.12093}, pmid = {24134302}, issn = {1365-2753}, mesh = {*Causality ; *Evidence-Based Practice ; Humans ; }, abstract = {In Causation and evidence-based practice: an ontological review, Kerry et al. argue that evidence-based practice (EBP) should revise its understanding of causation, and take on board a dispositionalist ontology. We point out that the challenges from complexity discussed by Kerry et al., are not properly addressed by their proposed ontology. Rather, the difference making views of causation Kerry et al. criticize, spell out the relevant aspects of causation, and have a range of advantages compared to dispositionalist accounts. We explore some of these here, with a special focus on the role of causal assumptions in inferences from scientific evidence to clinical decisions. A philosophical account should help us explicate the assumptions that go into causal inference in EBM. In doing so, it enables an understanding of the various ways in which these assumptions might fail, and of how they can be justified.}, } @article {pmid24126919, year = {2014}, author = {Silberberg, A and Allouch, C and Sandfort, S and Kearns, D and Karpel, H and Slotnick, B}, title = {Desire for social contact, not empathy, may explain "rescue" behavior in rats.}, journal = {Animal cognition}, volume = {17}, number = {3}, pages = {609-618}, doi = {10.1007/s10071-013-0692-1}, pmid = {24126919}, issn = {1435-9456}, mesh = {Animals ; *Empathy ; Female ; *Helping Behavior ; Rats ; Rats, Sprague-Dawley/*psychology ; *Social Behavior ; }, abstract = {Ben-Ami Bartal et al. (Science 334:1427-1430, 2011) showed that a rat in an open space (free rat) would touch the front door of a restraining tube to open its rear door, thereby enabling a rat trapped within (trapped rat) to enter a larger space that was farther away from the free rat. Since opening the rear door distanced the trapped rat from the free rat, Ben-Ami Bartal et al. argued free-rat behavior could not be motivated by the pursuit of social contact. Instead, this rat was empathically motivated, its goal being to reduce the presumed distress of the rat trapped in the restraining tube. In two experiments, we show that (a) a free rat will not learn to touch the front door to open the rear door when it is the first condition of the experiment; (b) over time, a trapped rat will often return to a restraining tube despite its presumed aversiveness; and (c) a free rat experienced in touching the front door will continue to touch it even if touching does not free the trapped rat. We explain these results and Ben-Ami Bartal et al.'s in terms of two processes, neophobia and the pursuit of social contact. When first placed in a restraining tube, neophobia causes the trapped rat to escape the tube when the rear door is opened. Across sessions, neophobia diminishes, permitting the rats' pursuit of social contact to emerge and dominate free- and trapped-rat behavior.}, } @article {pmid24125912, year = {2013}, author = {Yu, X and Chen, G and Zhang, S}, title = {A model for predicting the permeation of dimethyl sulfoxide into articular cartilage, and its application to the liquidus-tracking method.}, journal = {Cryobiology}, volume = {67}, number = {3}, pages = {332-338}, doi = {10.1016/j.cryobiol.2013.09.168}, pmid = {24125912}, issn = {1090-2392}, mesh = {Animals ; Cartilage, Articular/*metabolism ; Cryopreservation/methods ; Cryoprotective Agents/*metabolism ; Diffusion ; Dimethyl Sulfoxide/*metabolism ; Models, Biological ; Permeability ; Swine ; Thermodynamics ; }, abstract = {Long-term storage of articular cartilage (AC) has excited great interest due to the practical surgical significance of this tissue. The liquidus-tracking (LT) method developed by Pegg et al. (2006) [29] for vitreous preservation of AC achieved reasonable survival of post-warming chondrocytes in situ, but the design of the entire procedure was more dependent on trial and error. Mathematical modeling would help to better understand the LT process, and thereby make possible improvements to attain higher cell survival. Mass transfer plays a dominant role in the LT process. In the present study, a diffusion model based on the free-volume theory and the Flory-Huggins thermodynamics theory was developed to predict the permeation of dimethyl sulfoxide (Me2SO) into AC. A comparison between the predicted mean concentration of Me2SO in the AC disc and the experimental data over wide temperature and concentration ranges [-30 to 37 °C, 10 to 64.5% (w/w)] shows that the developed model can accurately describe the permeation of Me2SO into AC [coefficient of determination (R(2)): 0.951-1.000, mean relative error (MRE): 0.8-12.8%]. With this model, the spatial and temporal distribution of Me2SO in the AC disc during a loading/unloading process can be obtained. Application of the model to Pegg et al.'s LT procedure revealed that the liquidus line is virtually not followed for the center part of the AC disc. The presently developed model will be a useful tool in the analysis and design of the LT method for vitreous preservation of AC.}, } @article {pmid24103606, year = {2013}, author = {Howard, AM and Fragaszy, DM}, title = {Applying the bicoded spatial model to nonhuman primates in an arboreal multilayer environment.}, journal = {The Behavioral and brain sciences}, volume = {36}, number = {5}, pages = {552-3; discussion 571-87}, doi = {10.1017/S0140525X13000411}, pmid = {24103606}, issn = {1469-1825}, mesh = {Animals ; Cognition/*physiology ; Humans ; *Models, Neurological ; Space Perception/*physiology ; *Spatial Behavior ; }, abstract = {Applying the framework proposed by Jeffery et al. to nonhuman primates moving in multilayer arboreal and terrestrial environments, we see that these animals must generate a mosaic of many bicoded spaces in order to move efficiently and safely through their habitat. Terrestrial light detection and ranging (LiDAR) technology and three-dimensional modelling of canopy movement may permit testing of Jeffery et al.'s framework in natural environments.}, } @article {pmid24103605, year = {2013}, author = {Hölscher, C and Büchner, S and Strube, G}, title = {Multi-floor buildings and human wayfinding cognition.}, journal = {The Behavioral and brain sciences}, volume = {36}, number = {5}, pages = {551-2; discussion 571-87}, doi = {10.1017/S0140525X1300040X}, pmid = {24103605}, issn = {1469-1825}, mesh = {Animals ; Cognition/*physiology ; Humans ; *Models, Neurological ; Space Perception/*physiology ; *Spatial Behavior ; }, abstract = {Multilevel wayfinding research in environmental psychology and architecture exhibits a strong compatibility with Jeffery et al.'s "bicoded" representation of space. We identify a need for capturing verticality in spatial analysis techniques such as space syntax and argue for investigating inter-individual differences in the ability to mentally integrate the cognitive maps of separate floors in buildings.}, } @article {pmid24102837, year = {2013}, author = {Harrison, HB and Saenz-Agudelo, P and Planes, S and Jones, GP and Berumen, ML}, title = {On minimizing assignment errors and the trade-off between false positives and negatives in parentage analysis.}, journal = {Molecular ecology}, volume = {22}, number = {23}, pages = {5738-5742}, doi = {10.1111/mec.12527}, pmid = {24102837}, issn = {1365-294X}, mesh = {Genetics, Population/*methods ; *Models, Genetic ; }, abstract = {Genetic parentage analyses provide a practical means with which to identify parent-offspring relationships in the wild. In Harrison et al.'s study (2013a), we compare three methods of parentage analysis and showed that the number and diversity of microsatellite loci were the most important factors defining the accuracy of assignments. Our simulations revealed that an exclusion-Bayes theorem method was more susceptible to false-positive and false-negative assignments than other methods tested. Here, we analyse and discuss the trade-off between type I and type II errors in parentage analyses. We show that controlling for false-positive assignments, without reporting type II errors, can be misleading. Our findings illustrate the need to estimate and report both the rate of false-positive and false-negative assignments in parentage analyses.}, } @article {pmid24100089, year = {2014}, author = {Li, Q and Loke, AY}, title = {A literature review on the mutual impact of the spousal caregiver-cancer patients dyads: 'communication', 'reciprocal influence', and 'caregiver-patient congruence'.}, journal = {European journal of oncology nursing : the official journal of European Oncology Nursing Society}, volume = {18}, number = {1}, pages = {58-65}, doi = {10.1016/j.ejon.2013.09.003}, pmid = {24100089}, issn = {1532-2122}, mesh = {Age Factors ; Caregivers/*psychology ; China ; *Communication ; Female ; Humans ; Interpersonal Relations ; Male ; Neoplasms/psychology/*therapy ; *Quality of Life ; Risk Assessment ; Sex Factors ; Spouses/*psychology ; Stress, Psychological ; }, abstract = {PURPOSE: A diagnosis of cancer is the start of a journey of distress and adjustment for both the patient and his/her spouse. However, the dyadic phenomena are less conceptualised and related research is in the early stages. This review explores concepts of mutuality among spousal caregiver-cancer patient dyads and identifies directions for future research.

METHOD: A systematic search, including trawling through six electronic databases, a manual search, and an author search, was conducted to identity articles that had been published in English and Chinese from January 2000 to March 2013, using key terms related to caregiver-patients dyads in cancer care. An inductive content analysis approach was adopted to analyse and synthesise the concepts of spousal caregiver-cancer patient dyads.

RESULTS: Thirty-one articles were identified. The findings are described according to Fletcher et al.'s proposals for conceptualising spousal caregiver-patient dyads. The proposed concepts of 'communication', 'reciprocal influence', and 'caregiver-patient congruence' have been found to be interrelated, and to contribute to the spousal caregiver-patient dyads' mutual appraisal of caregiving and role adjustment through the cancer trajectory.

CONCLUSIONS: The findings highlight the importance of a perspective that focuses on the nature of the relationship between couples coping with cancer and the quality of their communication with each other. It is recognised that communication may act as a fundamental element of the abovementioned three concepts. Better communication between couples would probably facilitate reciprocal influence and caregiver-patient congruence, which in turn would have a positive effect on intimacy between the couple and improve the caregiving outcomes.}, } @article {pmid24099887, year = {2014}, author = {Cortez, D and Sharma, N and Devers, C and Devers, E and Schlegel, TT}, title = {Visual transform applications for estimating the spatial QRS-T angle from the conventional 12-lead ECG: Kors is still most Frank.}, journal = {Journal of electrocardiology}, volume = {47}, number = {1}, pages = {12-19}, doi = {10.1016/j.jelectrocard.2013.09.003}, pmid = {24099887}, issn = {1532-8430}, mesh = {*Algorithms ; Data Interpretation, Statistical ; Diagnosis, Computer-Assisted/*methods ; Female ; *Heart Rate ; Humans ; Male ; Middle Aged ; Myocardial Infarction/*diagnosis/*physiopathology ; Reproducibility of Results ; Sensitivity and Specificity ; Vectorcardiography/*methods ; }, abstract = {BACKGROUND: The 12-lead ECG-derived spatial QRS-T angle has prognostic and diagnostic utility, but most ECG machines currently fail to report it. The primary goal was to determine if reasonably accurate methods exist for rapid visual estimations of the spatial peaks QRS-T angle from conventional 12-lead ECG tracings.

METHODS AND RESULTS: Simultaneous 12-lead and Frank XYZ-lead recordings were obtained from a publicly available database for 100 post-myocardial infarction patients and 50 controls. ANOVA, Pearson's correlation coefficients and concordance plots were used to evaluate agreement for spatial peaks QRS-T angle results from the true Frank leads versus from several visually applied 12-to-Frank XYZ-lead transforms. The latter included Kors et al.'s regression and quasi-orthogonal, Bjerle and Arvedson's quasi-orthogonal, Dower's inverse, and Hyttinen et al.'s, Dawson et al.'s and Guillem et al.'s transforms. Spatial peaks QRS-T angles derived from the true Frank leads were not statistically significantly different from those derived from any visually applied transform. Of the visually applied transforms, the Kors' regression and Kors' quasi-orthogonal yielded the highest Pearson correlation coefficients against the gold-standard true Frank lead results [0.84 and 0.77, respectively, when individuals with bundle branch blocks were included (N=150), and 0.88 and 0.80, respectively, when individuals with bundle branch blocks were excluded (N=137)]. Bland-Altman 95% confidence intervals showed similar results, with the two Kors'-related methods also having the narrowest confidence intervals.

CONCLUSIONS: When visually applied, the Kors' regression-related and quasi-orthogonal transforms allow for reasonably precise spatial peaks QRS-T estimates and thus a potentially practical way to visually estimate spatial peaks QRS-T angles from conventional 12-lead ECGs.}, } @article {pmid24098100, year = {2013}, author = {Hannagan, T and Grainger, J}, title = {The lazy visual word form area: computational insights into location-sensitivity.}, journal = {PLoS computational biology}, volume = {9}, number = {10}, pages = {e1003250}, pmid = {24098100}, issn = {1553-7358}, mesh = {Computational Biology ; *Computer Simulation ; Humans ; *Models, Neurological ; Pattern Recognition, Visual/*physiology ; }, abstract = {In a recent study, Rauschecker et al. convincingly demonstrate that visual words evoke neural activation signals in the Visual Word Form Area that can be classified based on where they were presented in the visual fields. This result goes against the prevailing consensus, and begs an explanation. We show that one of the simplest possible models for word recognition, a multilayer feedforward network, will exhibit precisely the same behavior when trained to recognize words at different locations. The model suggests that the VWFA initially starts with information about location, which is not being suppressed during reading acquisition more than is needed to meet the requirements of location-invariant word recognition. Some new interpretations of Rauschecker et al.'s results are proposed, and three specific predictions are derived to be tested in further studies.}, } @article {pmid24095637, year = {2013}, author = {Banks, WE and d'Errico, F and Zilhão, J}, title = {Revisiting the chronology of the Proto-Aurignacian and the Early Aurignacian in Europe: a reply to Higham et al.'s comments on Banks et al. (2013).}, journal = {Journal of human evolution}, volume = {65}, number = {6}, pages = {810-817}, doi = {10.1016/j.jhevol.2013.08.004}, pmid = {24095637}, issn = {1095-8606}, mesh = {*Climate ; *Fossils ; Humans ; *Models, Biological ; }, } @article {pmid24094683, year = {2014}, author = {Bell, A and Jones, K}, title = {Don't birth cohorts matter? A commentary and simulation exercise on Reither, Hauser, and Yang's (2009) age-period-cohort study of obesity.}, journal = {Social science & medicine (1982)}, volume = {101}, number = {}, pages = {176-180}, doi = {10.1016/j.socscimed.2013.09.004}, pmid = {24094683}, issn = {1873-5347}, mesh = {*Cohort Effect ; Female ; *Health Status Disparities ; Humans ; Male ; Obesity/*epidemiology ; }, abstract = {Reither, Hauser, and Yang (2009) use a Hierarchical Age-Period-Cohort model (HAPC - Yang & Land, 2006) to assess changes in obesity in the USA population. Their results suggest that there is only a minimal effect of cohorts, and that it is periods which have driven the increase in obesity over time. We use simulations to show that this result may be incorrect. Using simulated data in which it is cohorts, rather than periods, that are responsible for the rise in obesity, we are able to replicate the period-trending results of Reither et al. In this instance, the HAPC model misses the true cohort trend entirely, erroneously finds a period trend, and underestimates the age trend. Reither et al.'s results may be correct, but because age, period and cohort are confounded there is no way to tell. This is typical of age-period-cohort models, and shows the importance of caution when any APC model is used. We finish with a discussion of ways forward for researchers wishing to model age, period and cohort in a robust and non-arbitrary manner.}, } @article {pmid24092916, year = {2015}, author = {Scammacca, NK and Roberts, G and Vaughn, S and Stuebing, KK}, title = {A Meta-Analysis of Interventions for Struggling Readers in Grades 4-12: 1980-2011.}, journal = {Journal of learning disabilities}, volume = {48}, number = {4}, pages = {369-390}, pmid = {24092916}, issn = {1538-4780}, support = {P50 HD052117/HD/NICHD NIH HHS/United States ; }, mesh = {Adolescent ; Child ; Dyslexia/*rehabilitation ; Education, Special/*statistics & numerical data ; Humans ; Outcome Assessment, Health Care/*statistics & numerical data ; }, abstract = {This meta-analysis synthesizes the literature on interventions for struggling readers in Grades 4 through 12 published between 1980 and 2011. It updates Scammacca et al.'s analysis of studies published between 1980 and 2004. The combined corpus of 82 study-wise effect sizes was meta-analyzed to determine (a) the overall effectiveness of reading interventions studied over the past 30 years, (b) how the magnitude of the effect varies based on student, intervention, and research design characteristics, and (c) what differences in effectiveness exist between more recent interventions and older ones. The analysis yielded a mean effect of 0.49, considerably smaller than the 0.95 mean effect reported in 2007. The mean effect for standardized measures was 0.21, also much smaller than the 0.42 mean effect reported in 2007. The mean effects for reading comprehension measures were similarly diminished. Results indicated that the mean effects for the 1980-2004 and 2005-2011 groups of studies were different to a statistically significant degree. The decline in effect sizes over time is attributed at least in part to increased use of standardized measures, more rigorous and complex research designs, differences in participant characteristics, and improvements in the school's "business-as-usual" instruction that often serves as the comparison condition in intervention studies.}, } @article {pmid24090906, year = {2013}, author = {Manninen, P and Collin, P}, title = {Reply to Dr. Selinger et al.'s letter.}, journal = {Journal of Crohn's & colitis}, volume = {7}, number = {12}, pages = {e715}, doi = {10.1016/j.crohns.2013.09.013}, pmid = {24090906}, issn = {1876-4479}, mesh = {Cell Transformation, Neoplastic/*pathology ; Colorectal Neoplasms/*epidemiology/*pathology ; Female ; Humans ; Inflammatory Bowel Diseases/*epidemiology/*pathology ; Male ; }, } @article {pmid24081943, year = {2013}, author = {Tsan, YT and Lee, CS and Ho, WC and Lin, MH and Wang, JD and Chen, PC}, title = {Reply to s. Bonovas et Al, s. Clement et Al, and j.L. Lund et Al.}, journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology}, volume = {31}, number = {32}, pages = {4162-4164}, doi = {10.1200/JCO.2013.51.7623}, pmid = {24081943}, issn = {1527-7755}, mesh = {Carcinoma, Hepatocellular/*etiology ; Female ; Hepatitis C/*complications ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/*adverse effects ; Liver Neoplasms/*etiology ; Male ; }, } @article {pmid24074998, year = {2013}, author = {Sharma, K and Goel, A and Gupta, S}, title = {Re: Okhunov et al.: S.T.O.N.E. nephrolithometry: novel surgical classification system for kidney calculi (Urology 2013;81:1154-1160).}, journal = {Urology}, volume = {82}, number = {4}, pages = {979}, doi = {10.1016/j.urology.2013.05.041}, pmid = {24074998}, issn = {1527-9995}, mesh = {Female ; Hemorrhage/*etiology ; Humans ; Kidney Calculi/*classification/*diagnostic imaging ; Male ; *Tomography, X-Ray Computed ; }, } @article {pmid24072700, year = {2014}, author = {Boaz, A and Morgan, M}, title = {Working to establish 'normality' post-transplant: a qualitative study of kidney transplant patients.}, journal = {Chronic illness}, volume = {10}, number = {4}, pages = {247-258}, doi = {10.1177/1742395313504789}, pmid = {24072700}, issn = {1745-9206}, mesh = {Adaptation, Psychological ; Adult ; Age Factors ; Aged ; Attitude to Health ; Female ; Graft Rejection/psychology ; *Health ; Humans ; Kidney Transplantation/*psychology/*rehabilitation ; Male ; Middle Aged ; Patients/*psychology ; Postoperative Period ; Qualitative Research ; Quality of Life ; Sex Factors ; Surveys and Questionnaires ; }, abstract = {OBJECTIVES: To explore patients' perceptions and experiences of 'normality' and the influences on this at three time points post-transplant.

METHODS: In-depth interviews with 25 patients at three months, one year and more than three years following kidney transplant. Patients' accounts were compared with Sanderson et al.'s typology of types of normality.

FINDINGS: Post-transplant, patients worked hard to re-establish normality, albeit in a 'reset' form. This normality was a very personal construct, shaped by a wide range of factors including age, gender and personal circumstances. Some patients encountered significant challenges in regaining normality, both at three months for those experiencing acute and distressing side effects, and later relating to the long-term side effects of transplant medication and co-morbidities. However, the most dramatic threat to normality (disrupted normality) came from episodes of rejection and transplant failure.

CONCLUSIONS: The main types of normality achieved vary for different conditions. Moreover, despite improvements in health post-transplant and opportunities to build a new, reset normality, the participants recognised the need to pay careful attention to the spectre of future ill health and transplant failure. Transplant failure was therefore a source of disruption that was central to their illness narratives and perceived as an ever present risk.}, } @article {pmid24067421, year = {2013}, author = {Su, Y and Zhao, L and Min, L}, title = {Analysis and simulation of an Adefovir anti-hepatitis B virus infection therapy immune model with alanine aminotransferase.}, journal = {IET systems biology}, volume = {7}, number = {5}, pages = {205-213}, pmid = {24067421}, issn = {1751-8849}, mesh = {Adenine/*analogs & derivatives/therapeutic use ; Alanine Transaminase/*chemistry ; Algorithms ; Antiviral Agents/*therapeutic use ; Computer Simulation ; DNA, Viral/metabolism ; Hepatitis B/*drug therapy ; Hepatitis B virus/*immunology ; Hepatocytes/metabolism/virology ; Humans ; Immune System ; Liver/metabolism ; Organophosphonates/*therapeutic use ; T-Lymphocytes, Cytotoxic/metabolism ; }, abstract = {Hepatitis B virus (HBV) infection models and anti-HBV infection therapy models have been set up to understand and explain clinical phenomena. Many of these models have been proposed based on Zeuzem et al. and Nowak et al.'s basic virus infection model (BVIM). Some references have pointed out that the basic infection reproductive number of the BVIM is biologically questionable and gave the modified models with standard mass action incidences. This study describes one anti-HBV therapy immune model with alanine aminotransferase (ALT) based on standard mass action incidences. There are two basic infection reproductive numbers R0 and R1 in the model. It is proved that if R0 < 1 and R1 < 1, the disease free equilibrium is locally and globally asymptotically stable, respectively. For the endemic equilibrium, simulation shows that if R1 > 1, it may be also globally asymptotically stable. Simulations based on clinical data of HBV DNA and ALT can explain some clinical phenomena. Simulations of the correlation between liver cells, HBV DNA, cytotoxic T lymphocytes and ALT are also given.}, } @article {pmid24051827, year = {2013}, author = {Im, JF and McGuffin, MJ and Leung, R}, title = {GPLOM: the generalized plot matrix for visualizing multidimensional multivariate data.}, journal = {IEEE transactions on visualization and computer graphics}, volume = {19}, number = {12}, pages = {2606-2614}, doi = {10.1109/TVCG.2013.160}, pmid = {24051827}, issn = {1941-0506}, mesh = {*Algorithms ; *Computer Graphics ; Information Storage and Retrieval/*methods ; *Multivariate Analysis ; Reproducibility of Results ; Sensitivity and Specificity ; *Software ; *User-Computer Interface ; }, abstract = {Scatterplot matrices (SPLOMs), parallel coordinates, and glyphs can all be used to visualize the multiple continuous variables (i.e., dependent variables or measures) in multidimensional multivariate data. However, these techniques are not well suited to visualizing many categorical variables (i.e., independent variables or dimensions). To visualize multiple categorical variables, 'hierarchical axes' that 'stack dimensions' have been used in systems like Polaris and Tableau. However, this approach does not scale well beyond a small number of categorical variables. Emerson et al. [8] extend the matrix paradigm of the SPLOM to simultaneously visualize several categorical and continuous variables, displaying many kinds of charts in the matrix depending on the kinds of variables involved. We propose a variant of their technique, called the Generalized Plot Matrix (GPLOM). The GPLOM restricts Emerson et al.'s technique to only three kinds of charts (scatterplots for pairs of continuous variables, heatmaps for pairs of categorical variables, and barcharts for pairings of categorical and continuous variable), in an effort to make it easier to understand. At the same time, the GPLOM extends Emerson et al.'s work by demonstrating interactive techniques suited to the matrix of charts. We discuss the visual design and interactive features of our GPLOM prototype, including a textual search feature allowing users to quickly locate values or variables by name. We also present a user study that compared performance with Tableau and our GPLOM prototype, that found that GPLOM is significantly faster in certain cases, and not significantly slower in other cases.}, } @article {pmid24044580, year = {2013}, author = {Huang, M and Wang, L and Ma, H and Wang, J and Xiang, M}, title = {Lack of an association between interleukin-6 -174G/C polymorphism and circulating interleukin-6 levels in normal population: a meta-analysis.}, journal = {DNA and cell biology}, volume = {32}, number = {11}, pages = {654-664}, doi = {10.1089/dna.2013.2148}, pmid = {24044580}, issn = {1557-7430}, mesh = {Coronary Disease/genetics ; Genetic Predisposition to Disease ; Heterozygote ; Humans ; Interleukin-6/*blood/*genetics ; *Polymorphism, Single Nucleotide ; Reference Values ; }, abstract = {Interleukin-6 (IL-6) signaling may play a causal role in the development of coronary heart disease. However, the relationship between IL-6 genotypes and plasma levels of IL-6 appears to be complex. To help clarify the inconsistent findings, we conducted a meta-analysis of the published genetic association studies of the -174 G/C polymorphisms in the IL-6 gene and the circulating IL-6 levels in a normal population. In this meta-analysis, no significant association of IL-6 -174G/C polymorphism and circulating IL-6 levels in a normal population was observed. However, when compared among GG, GC, and CC genotypes, heterogeneity existed among the studies. Sensitivity analysis revealed that, the independent study by Shen et al. influenced the heterogeneity in the homozygous and heterozygous comparison. Although Shen et al.'s study was excluded, no significant association was observed between IL-6 -174G/C polymorphism and circulating IL-6 levels in a normal population [homozygous comparison (GG vs. CC): the pooled standard mean difference (SMD) was -0.01, 95% confidence interval (CI): -0.1-0.08; heterozygous comparison (GC vs. GG or CC): the pooled SMD (GG vs. GC) was -0.05, 95%CI: -0.11-0.01, and the pooled SMD (CC vs. GC) was 0.03, 95%CI: -0.03-0.1]. Under the dominant model, the pooled SMD was -0.05, 95%CI: -0.11-0.01). The meta-analysis provides evidence that the -174G/C polymorphism in the IL-6 gene is not significantly associated with circulating IL-6 levels in a normal population.}, } @article {pmid24043434, year = {2013}, author = {Wiebe, ER}, title = {Invited commentary: How can we reconcile the findings of Keyes et al.'s study with the experience of our patients in clinical practice?.}, journal = {American journal of epidemiology}, volume = {178}, number = {9}, pages = {1389-1391}, doi = {10.1093/aje/kwt186}, pmid = {24043434}, issn = {1476-6256}, mesh = {Contraceptive Agents, Female/*adverse effects ; Depression/*chemically induced ; Estrogens/*adverse effects ; Female ; Humans ; Progestins/*adverse effects ; }, abstract = {Although the accompanying study by Keyes et al. (Am J Epidemiol. 2013;178(9):1378-1388) shows us that women currently using hormonal contraception (HC) have better scores on the Center for Epidemiologic Studies Depression Scale and report fewer suicide attempts, it does not show us that HC protects women from mood disorders or that HC is free of the mood-related side effects which cause high rates of discontinuation. The groups compared in the Keyes et al. study were different in many ways; the women using HC were younger, were more likely to engage in positive health behaviors, and had lower depression scores at each prior interview. Women with mood disorders are more likely to avoid or discontinue HC and more likely to experience worsening mood while on HC. The negative mood-related side effects experienced by women using HC (irritability and lability) are not captured by a screening tool for clinical depression, such as the depression scale used in this study. The database used in this study was longitudinal and multiwave, so the authors could have compared changes in depressive symptoms among women who switched from hormonal to nonhormonal contraceptive methods (and vice versa) across different waves. Only if the same women experienced greater levels of depressive symptoms after discontinuing HC and fewer symptoms when they restarted HC could we conclude that HC may protect women from mood disorders.}, } @article {pmid24029443, year = {2013}, author = {Lobatón, T and Rodríguez-Moranta, F and Guardiola, J}, title = {Reply to Dr. Papamichael et al.'s letter.}, journal = {Journal of Crohn's & colitis}, volume = {7}, number = {12}, pages = {e702-3}, doi = {10.1016/j.crohns.2013.08.011}, pmid = {24029443}, issn = {1876-4479}, mesh = {Crohn Disease/*metabolism/*pathology ; Feces/*chemistry ; Female ; Humans ; Leukocyte L1 Antigen Complex/*analysis ; Male ; }, } @article {pmid24021849, year = {2013}, author = {Langdon, R and Finkbeiner, M and Connors, MH and Connaughton, E}, title = {Masked and unmasked priming in schizophrenia.}, journal = {Consciousness and cognition}, volume = {22}, number = {4}, pages = {1206-1213}, doi = {10.1016/j.concog.2013.07.009}, pmid = {24021849}, issn = {1090-2376}, mesh = {Adult ; Case-Control Studies ; Consciousness/*physiology ; Female ; Humans ; Male ; Middle Aged ; Perceptual Masking/*physiology ; Psychomotor Performance ; Reaction Time ; Repetition Priming/*physiology ; Schizophrenia/*physiopathology ; *Schizophrenic Psychology ; }, abstract = {Dehaene et al. (2003) showed an absence of conscious, but not masked, conflict effects when patients with schizophrenia performed a number-categorisation priming task. We aimed to replicate these influential results using a different word-categorisation priming task. Counter to Dehaene et al.'s findings, 21 patients and 20 healthy controls showed similar congruence effects for both masked and visible primes. Within patients, a reduced congruence effect for visible primes associated with longer duration of illness and more severe behavioural disorganisation. Patients, unlike controls, were no slower to respond to targets that followed visible compared to masked primes. Conscious conflict effects on priming tasks are not universally reduced in schizophrenia but may associate with chronicity and behavioural disorganisation. That patients were no slower when the preceding primes were clearly visible accords with evidence elsewhere that information processing in schizophrenia is driven more by immediate conscious experience and constrained less by prior events.}, } @article {pmid24020857, year = {2014}, author = {Veld, M and Van De Voorde, K}, title = {How to take care of nurses in your organization: two types of exchange relationships compared.}, journal = {Journal of advanced nursing}, volume = {70}, number = {4}, pages = {855-865}, doi = {10.1111/jan.12247}, pmid = {24020857}, issn = {1365-2648}, mesh = {Cross-Sectional Studies ; Netherlands ; *Nursing Staff ; *Workplace ; }, abstract = {AIM: To explore the relationships between climate for well-being, economic and social exchange, affective ward commitment and job strain among nurses in the Netherlands.

BACKGROUND: This study focuses on the immediate work environment of nurses by exploring the way nurse perceptions about the extent to which the ward values and cares for their welfare influence their levels of affective ward commitment and job strain. Second, this study extends previous research on exchange relationships by examining the potential differential impact of social and economic exchange relationships on commitment and job strain.

DESIGN: A cross-sectional survey among nurses.

METHODS: The study was conducted in the Netherlands in 2011. Validated measures of climate for well-being, social exchange, economic exchange, ward commitment and job strain were used. Hypotheses were tested using regression analyses. MacKinnon et al.'s (2007) guidelines to assess mediation were used.

RESULTS: The response rate was 41% (271 questionnaires). The results show that climate for well-being positively influences social exchange relationships, which are in turn associated with enhanced ward commitment and reduced strain. Climate for well-being negatively influences evaluations of economic exchange, which are in turn negatively related to ward commitment.

CONCLUSION: This study shows that nurses use the information available in their immediate work environment to evaluate their exchange relationship with the organization. Second, the findings point towards the importance of economic and social exchange relationships as a mechanism between climate for well-being on the one hand and affective ward commitment and job strain on the other hand.}, } @article {pmid24019096, year = {2013}, author = {Kulathinal, RJ}, title = {Functional genetics in the post-genomics era: building a better roadmap in Drosophila.}, journal = {G3 (Bethesda, Md.)}, volume = {3}, number = {9}, pages = {1451-1452}, pmid = {24019096}, issn = {2160-1836}, mesh = {Animals ; DNA Primers/*metabolism ; *Databases, Genetic ; Drosophila melanogaster/*genetics ; Molecular Sequence Annotation/*methods ; *RNA Interference ; RNA, Small Interfering/*genetics ; *Software ; }, abstract = {In this commentary, Rob Kulathinal describes two papers from the Perrimon laboratory, each describing a new online resource that can assist geneticists with the design of their RNAi experiments. Hu et al.'s "UP-TORR: online tool for accurate and up-to-date annotation of RNAi reagents" and "FlyPrimerBank: An online database for Drosophila melanogaster gene expression analysis and knockdown evaluation of RNAi reagents" are published, respectively, in this month's issue of GENETICS and G3: Genes|Genomes|Genetics.}, } @article {pmid24018958, year = {2013}, author = {Lee, CC and Hsu, CW and Lai, YM and Vasilakos, A}, title = {An enhanced mobile-healthcare emergency system based on extended chaotic maps.}, journal = {Journal of medical systems}, volume = {37}, number = {5}, pages = {9973}, pmid = {24018958}, issn = {1573-689X}, mesh = {Computer Communication Networks ; *Computer Security ; *Confidentiality ; Humans ; Privacy ; Telemedicine ; }, abstract = {Mobile Healthcare (m-Healthcare) systems, namely smartphone applications of pervasive computing that utilize wireless body sensor networks (BSNs), have recently been proposed to provide smartphone users with health monitoring services and received great attentions. An m-Healthcare system with flaws, however, may leak out the smartphone user's personal information and cause security, privacy preservation, or user anonymity problems. In 2012, Lu et al. proposed a secure and privacy-preserving opportunistic computing (SPOC) framework for mobile-Healthcare emergency. The brilliant SPOC framework can opportunistically gather resources on the smartphone such as computing power and energy to process the computing-intensive personal health information (PHI) in case of an m-Healthcare emergency with minimal privacy disclosure. To balance between the hazard of PHI privacy disclosure and the necessity of PHI processing and transmission in m-Healthcare emergency, in their SPOC framework, Lu et al. introduced an efficient user-centric privacy access control system which they built on the basis of an attribute-based access control mechanism and a new privacy-preserving scalar product computation (PPSPC) technique. However, we found out that Lu et al.'s protocol still has some secure flaws such as user anonymity and mutual authentication. To fix those problems and further enhance the computation efficiency of Lu et al.'s protocol, in this article, the authors will present an improved mobile-Healthcare emergency system based on extended chaotic maps. The new system is capable of not only providing flawless user anonymity and mutual authentication but also reducing the computation cost.}, } @article {pmid24018766, year = {2013}, author = {Kulathinal, RJ}, title = {Functional genetics in the post-genomics era: building a better roadmap in Drosophila.}, journal = {Genetics}, volume = {195}, number = {1}, pages = {7-8}, pmid = {24018766}, issn = {1943-2631}, mesh = {Animals ; Molecular Sequence Annotation/*methods ; *RNA Interference ; RNA, Small Interfering/*genetics ; *Software ; }, abstract = {In this commentary, Rob Kulathinal describes two articles from the Perrimon lab, each describing a new online resource that can assist geneticists with the design of their RNA interference (RNAi) experiments. Hu et al.'s "UP-TORR: online tool for accurate and up-to-date annotation of RNAi reagents" and "FlyPrimerBank: An online database for Drosophila melanogaster gene expression analysis and knockdown evaluation of RNAi reagents" are published, respectively, in this month's issues of GENETICS and G3.}, } @article {pmid24014933, year = {2013}, author = {Kim, I and Pang, H and Zhao, H}, title = {Statistical properties on semiparametric regression for evaluating pathway effects.}, journal = {Journal of statistical planning and inference}, volume = {143}, number = {4}, pages = {745-763}, pmid = {24014933}, issn = {0378-3758}, support = {N01 HV028186/HV/NHLBI NIH HHS/United States ; P30 AG021342/AG/NIA NIH HHS/United States ; P30 DA018343/DA/NIDA NIH HHS/United States ; R01 GM059507/GM/NIGMS NIH HHS/United States ; }, abstract = {Most statistical methods for microarray data analysis consider one gene at a time, and they may miss subtle changes at the single gene level. This limitation may be overcome by considering a set of genes simultaneously where the gene sets are derived from prior biological knowledge. We call a pathway as a predefined set of genes that serve a particular cellular or physiological function. Limited work has been done in the regression settings to study the effects of clinical covariates and expression levels of genes in a pathway on a continuous clinical outcome. A semiparametric regression approach for identifying pathways related to a continuous outcome was proposed by Liu et al. (2007), who demonstrated the connection between a least squares kernel machine for nonparametric pathway effect and a restricted maximum likelihood (REML) for variance components. However, the asymptotic properties on a semiparametric regression for identifying pathway have never been studied. In this paper, we study the asymptotic properties of the parameter estimates on semiparametric regression and compare Liu et al.'s REML with our REML obtained from a profile likelihood. We prove that both approaches provide consistent estimators, have [Formula: see text] convergence rate under regularity conditions, and have either an asymptotically normal distribution or a mixture of normal distributions. However, the estimators based on our REML obtained from a profile likelihood have a theoretically smaller mean squared error than those of Liu et al.'s REML. Simulation study supports this theoretical result. A profile restricted likelihood ratio test is also provided for the non-standard testing problem. We apply our approach to a type II diabetes data set (Mootha et al., 2003).}, } @article {pmid24004287, year = {2013}, author = {Hayami, W and Momozawa, A and Otani, S}, title = {Effect of defects in the formation of AlB2-type WB2 and MoB2.}, journal = {Inorganic chemistry}, volume = {52}, number = {13}, pages = {7573-7577}, doi = {10.1021/ic400587j}, pmid = {24004287}, issn = {1520-510X}, abstract = {Tungsten diboride, WB2, usually has a hexagonal structure with the space group P63/mmc (number 194); and molybdenum diboride, MoB2, has a trigonal structure with R3̅m (number 166). Other than these phases, both diborides are reported to have a phase with an AlB2-type structure (P6/mmm, number 191). AlB2-type MoB2 is easy to synthesize and has been extensively studied, whereas AlB2-type WB2 is very difficult to synthesize and has appeared only once in a report by Woods et al. in 1966 (Woods, H. P.; Wawner, Jr., F. E.; Fox, B. G. Science1966, 151, 75.) We have investigated these diborides by means of first-principles calculations and found that boron defects are responsible for the difference in their synthesizability. AlB2-type MoB2 became stable enough with some boron defects added, while AlB2-type WB2 became minimally stable, suggesting it may not actually exist. Following our calculations, we attempted to synthesize AlB2-type WB2 with the optimum quantity of boron defects but observed no trace of it. We conclude, from both calculations and experiments, that AlB2-type WB2 does not exist stably in the W-B phase diagram and that the compound produced in Woods et al.'s report might have contained some impurities.}, } @article {pmid23993082, year = {2013}, author = {Fowler, J}, title = {Bioeffect Modeling and equieffective dose concepts in radiation oncology: comments on Bentzen et al.'s paper from ICRU in Radiother Oncol 2012;105:266-268.}, journal = {Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology}, volume = {108}, number = {2}, pages = {354}, doi = {10.1016/j.radonc.2013.07.009}, pmid = {23993082}, issn = {1879-0887}, mesh = {Humans ; Neoplasms/*radiotherapy ; *Radiotherapy Dosage ; }, } @article {pmid23988384, year = {2013}, author = {Borji, A and Sihite, DN and Itti, L}, title = {Objects do not predict fixations better than early saliency: a re-analysis of Einhauser et al.'s data.}, journal = {Journal of vision}, volume = {13}, number = {10}, pages = {18}, doi = {10.1167/13.10.18}, pmid = {23988384}, issn = {1534-7362}, mesh = {Female ; Fixation, Ocular/*physiology ; Humans ; Male ; *Models, Psychological ; Pattern Recognition, Visual/*physiology ; }, abstract = {Einhäuser, Spain, and Perona (2008) explored an alternative hypothesis to saliency maps (i.e., spatial image outliers) and claimed that "objects predict fixations better than early saliency." To test their hypothesis, they measured eye movements of human observers while they inspected 93 photographs of common natural scenes (Uncommon Places dataset by Shore, Tillman, & Schmidt-Wulen 2004; Supplement Figure S4). Subjects were asked to observe an image and, immediately afterwards, to name objects they saw (remembered). Einhäuser et al. showed that a map made of manually drawn object regions, each object weighted by its recall frequency, predicts fixations in individual images better than early saliency. Due to important implications of this hypothesis, we investigate it further. The core of our analysis is explained here. Please refer to the Supplement for details.}, } @article {pmid23973183, year = {2013}, author = {den Dekker, MH and Slieker, MG and Blank, AC and Haas, F and Freund, MW}, title = {Comparability of Z-score equations of cardiac structures in hypoplastic left heart complex.}, journal = {Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography}, volume = {26}, number = {11}, pages = {1314-1321}, doi = {10.1016/j.echo.2013.07.022}, pmid = {23973183}, issn = {1097-6795}, mesh = {*Algorithms ; Aortic Valve/*diagnostic imaging ; Echocardiography/*methods ; Female ; Humans ; Hypoplastic Left Heart Syndrome/*diagnostic imaging ; Image Enhancement/methods ; Infant, Newborn ; Male ; Mitral Valve/*diagnostic imaging ; Reproducibility of Results ; Sensitivity and Specificity ; }, abstract = {BACKGROUND: Hypoplastic left heart complex (HLHC) is characterized by a mitral valve or an aortic valve annular Z score < -2, antegrade flow in the ascending aorta, ductal dependency, coarctation or aortic arch hypoplasia, and absence of significant (sub)valvar stenosis. The Z scores of the mitral and aortic valve annuli are major determinants of HLHC. Therefore, the algorithm for Z-score calculation is essential for diagnosis. However, no single universal method of calculation is in use. In the scientific literature addressing HLHC, various Z-score calculation methods have been applied. The aim of this study was to evaluate Z scores derived from two-dimensional echocardiographic dimensions in patients with HLHC.

METHODS: To compare the different published methods using two-dimensional echocardiographic measures for Z-score calculation, a cohort of 18 newborns diagnosed with HLHC was retrospectively evaluated. In addition, the methods to determine body surface area in newborns were evaluated.

RESULTS: Three Z-score calculation methods were included and compared. Using the method of Daubeney et al. to calculate Z scores in our cohort illustrated a lack of correlation beyond a Z score < 0, compared with the methods of Zilberman et al. and Pettersen et al. Z scores calculated using Zilberman et al.'s and Pettersen et al.'s methods were fairly consistent. The equations used by Pettersen et al. are based on the largest population of neonates.

CONCLUSION: Although the different methods for calculating Z scores for mitral and aortic valve dimensions correspond fairly well in the normal range, Z scores < -2 diverge substantially. A useful scientific comparison of published data and outcomes of patients with HLHC remains elusive. The Z-score calculation algorithms used by Pettersen et al. appear to be the most appropriate for use in an evaluation of HLHC. Because these different methods can yield different values, reporting the method as well as the Z score is essential for an accurate diagnosis. Similarly, the method used to determine body surface area should be reported.}, } @article {pmid23972094, year = {2014}, author = {Song, X and Chen, J and Proctor, RW}, title = {Correspondence effects with torches: grasping affordance or visual feature asymmetry?.}, journal = {Quarterly journal of experimental psychology (2006)}, volume = {67}, number = {4}, pages = {665-675}, doi = {10.1080/17470218.2013.824996}, pmid = {23972094}, issn = {1747-0226}, mesh = {Analysis of Variance ; Attention/*physiology ; Female ; *Functional Laterality ; Hand Strength/*physiology ; Humans ; Judgment/*physiology ; Male ; Photic Stimulation ; Reaction Time/physiology ; Size Perception/*physiology ; Space Perception/physiology ; Students ; Universities ; }, abstract = {Three experiments were conducted to determine whether an object-based correspondence effect for torch (flashlight) stimuli reported by Pellicano et al. [(2010). Simon-like and functional affordance effects with tools: The effects of object perceptual discrimination and object action state. Quarterly Journal of Experimental Psychology, 63, 2190-2201] is due to a grasping affordance provided by the handle or asymmetry of feature markings on the torch. In Experiment 1 the stimuli were the same as those from Pellicano et al.'s Experiment 2, whereas in Experiments 2 and 3 the stimuli were modified versions with the graspable handle removed. Participants in all experiments performed upright/inverted orientation judgements on the torch stimuli. The results of Experiment 1 replicated those of Pellicano et al.: A small but significant object-based correspondence effect was evident, mainly when the torch was in an active state. With the handle of the torch removed in Experiment 2, making the barrel markings more asymmetric in the display, the correspondence effect was larger. Experiment 3 directly demonstrated an effect of barrel-marking asymmetry on the correspondence effect: When only the half of the markings nearest the light end of the torch was included, the correspondence effect reversed to favour the light end. The results are in agreement with a visual feature-asymmetry account and are difficult to reconcile with a grasping-affordance account.}, } @article {pmid23968281, year = {2013}, author = {Mussa, HY and Mitchell, JB and Glen, RC}, title = {Full "Laplacianised" posterior naive Bayesian algorithm.}, journal = {Journal of cheminformatics}, volume = {5}, number = {1}, pages = {37}, pmid = {23968281}, issn = {1758-2946}, abstract = {BACKGROUND: In the last decade the standard Naive Bayes (SNB) algorithm has been widely employed in multi-class classification problems in cheminformatics. This popularity is mainly due to the fact that the algorithm is simple to implement and in many cases yields respectable classification results. Using clever heuristic arguments "anchored" by insightful cheminformatics knowledge, Xia et al. have simplified the SNB algorithm further and termed it the Laplacian Corrected Modified Naive Bayes (LCMNB) approach, which has been widely used in cheminformatics since its publication.In this note we mathematically illustrate the conditions under which Xia et al.'s simplification holds. It is our hope that this clarification could help Naive Bayes practitioners in deciding when it is appropriate to employ the LCMNB algorithm to classify large chemical datasets.

RESULTS: A general formulation that subsumes the simplified Naive Bayes version is presented. Unlike the widely used NB method, the Standard Naive Bayes description presented in this work is discriminative (not generative) in nature, which may lead to possible further applications of the SNB method.

CONCLUSIONS: Starting from a standard Naive Bayes (SNB) algorithm, we have derived mathematically the relationship between Xia et al.'s ingenious, but heuristic algorithm, and the SNB approach. We have also demonstrated the conditions under which Xia et al.'s crucial assumptions hold. We therefore hope that the new insight and recommendations provided can be found useful by the cheminformatics community.}, } @article {pmid23964814, year = {2013}, author = {Pascual-Leone, A and Rodriguez-Rubio, B and Metler, S}, title = {What else are psychotherapy trainees learning? A qualitative model of students' personal experiences based on two populations.}, journal = {Psychotherapy research : journal of the Society for Psychotherapy Research}, volume = {23}, number = {5}, pages = {578-591}, doi = {10.1080/10503307.2013.807379}, pmid = {23964814}, issn = {1468-4381}, mesh = {Adult ; Educational Measurement ; Female ; Humans ; Male ; Middle Aged ; Models, Theoretical ; Psychology, Clinical/education ; Psychotherapy/*education ; Students, Health Occupations/*psychology ; Young Adult ; }, abstract = {After an introductory course in experiential-integrative psychotherapy, 21 graduate students provided personal narratives of their experiences, which were analyzed using the grounded theory method. Results produced 37 hierarchically organized experiences, revealing that students perceived multiple changes in both professional (i.e., skill acquisition and learning related to the therapeutic process) and personal (i.e., self growth in a more private sphere) domains. Analysis also highlighted key areas of difficulties in training. By adding the personal accounts of graduate trainees, this study enriches and extends Pascual-Leone et al.'s (2012) findings on undergraduates' experiences, raising the number of cases represented in the model to 45. Findings confirm the model of novice trainee experiences while highlighting the unique experiences of undergraduate vs. graduate trainees.}, } @article {pmid23959271, year = {2013}, author = {Beaujean, AA and Limbers, CA and Varni, JW}, title = {Commentary on strengthening the assessment of factorial invariance across population subgroups: a commentary on Varni et al. (2013).}, journal = {Quality of life research : an international journal of quality of life aspects of treatment, care and rehabilitation}, volume = {}, number = {}, pages = {}, pmid = {23959271}, issn = {1573-2649}, abstract = {In his commentary on Varni et al.'s (Qual Life Res. doi: 10.1007/s11136-013-0370-4 , 2013) article, McIntosh (Qual Life Res. doi: 10.1007/s11136-013-0465-y , 2013) has two main arguments. First, we should have paid more attention to statistical tests (i.e., χ [2] values) instead of approximate fit indexes for our analysis, especially with the baseline model. Second, Bayesian methods are better than the frequentist methods we used in determining the model's invariance across age and gender groups. We believe that statistical tests do have a place in assessing model fit, but overemphasis on them, especially with larger sample sizes, can lead to errant decisions. Second, while we agree that Bayesian methods have the potential to contribute much to the field of assessing invariance, more development needs to be conducted before they can be widely utilized in assessing factorial invariance across groups.}, } @article {pmid23954929, year = {2014}, author = {Carter, MD and Crow, BS and Pantazides, BG and Watson, CM and DeCastro, BR and Thomas, JD and Blake, TA and Johnson, RC}, title = {Profiling cholinesterase adduction: a high-throughput prioritization method for organophosphate exposure samples.}, journal = {Journal of biomolecular screening}, volume = {19}, number = {2}, pages = {325-330}, pmid = {23954929}, issn = {1552-454X}, support = {CC999999/ImCDC/Intramural CDC HHS/United States ; OT12-010/OT/OSTLTS CDC HHS/United States ; }, mesh = {Butyrylcholinesterase/blood/chemistry ; Cholinesterase Inhibitors/*chemistry ; Cholinesterases/*chemistry ; Chromatography, Liquid ; *High-Throughput Screening Assays ; Humans ; Mass Spectrometry ; Organophosphorus Compounds/*chemistry ; }, abstract = {A high-throughput prioritization method was developed for use with a validated confirmatory method detecting organophosphorus nerve agent exposure by immunomagnetic separation high-performance liquid chromatography tandem mass spectrometry. A ballistic gradient was incorporated into this analytical method to profile unadducted butyrylcholinesterase (BChE) in clinical samples. With Zhang et al.'s Z' factor of 0.88 ± 0.01 (SD) of control analytes and Z factor of 0.25 ± 0.06 (SD) of serum samples, the assay is rated an "excellent assay" for the synthetic peptide controls used and a "double assay" when used to prioritize clinical samples. Hits, defined as samples containing BChE Ser-198 adducts or no BChE present, were analyzed in a confirmatory method for identification and quantitation of the BChE adduct, if present. The ability to prioritize samples by highest exposure for confirmatory analysis is of particular importance in an exposure to cholinesterase inhibitors such as organophosphorus nerve agents, in which a large number of clinical samples may be collected. In an initial blind screen, 67 of 70 samples were accurately identified, giving an assay accuracy of 96%, and it yielded no false-negatives. The method is the first to provide a high-throughput prioritization assay for profiling adduction of Ser-198 BChE in clinical samples.}, } @article {pmid23931928, year = {2014}, author = {Agius, NM and Wilkinson, A}, title = {Students' and teachers' views of written feedback at undergraduate level: a literature review.}, journal = {Nurse education today}, volume = {34}, number = {4}, pages = {552-559}, doi = {10.1016/j.nedt.2013.07.005}, pmid = {23931928}, issn = {1532-2793}, mesh = {*Education, Nursing, Baccalaureate ; *Educational Measurement ; Faculty, Nursing ; *Feedback ; Humans ; Students, Nursing/psychology ; *Writing ; }, abstract = {OBJECTIVES: To explore undergraduate students' expectations and teachers' views of written feedback.

DESIGN: Narrative literature review.

DATA SOURCES: Seven electronic databases were searched for primary research published in English with additional manual searches and reference tracking.

REVIEW METHODS: Systematic approach to search strategy, selection and appraisal of papers, data extraction and synthesis following Hawker et al.'s (2002) guidelines.

RESULTS: 21 studies met the inclusion criteria. Four student themes were identified concerning written feedback: quality, quantity and location of feedback, feed-forward and timeliness. Teachers reported that time pressures, institutional policies, and administrative issues affect feedback provision.

CONCLUSIONS: Rigorous research is needed to gain a better understanding of students' expectations of written feedback. Strategies need to be adopted to meet students' expectations and educate students to take an active role and reflect on the feedback received.}, } @article {pmid23923099, year = {2013}, author = {Giustini, D and Boulos, MN}, title = {Google Scholar is not enough to be used alone for systematic reviews.}, journal = {Online journal of public health informatics}, volume = {5}, number = {2}, pages = {214}, pmid = {23923099}, issn = {1947-2579}, abstract = {BACKGROUND: Google Scholar (GS) has been noted for its ability to search broadly for important references in the literature. Gehanno et al. recently examined GS in their study: 'Is Google scholar enough to be used alone for systematic reviews?' In this paper, we revisit this important question, and some of Gehanno et al.'s other findings in evaluating the academic search engine.

METHODS: The authors searched for a recent systematic review (SR) of comparable size to run search tests similar to those in Gehanno et al. We selected Chou et al. (2013) contacting the authors for a list of publications they found in their SR on social media in health. We queried GS for each of those 506 titles (in quotes ""), one by one. When GS failed to retrieve a paper, or produced too many results, we used the allintitle: command to find papers with the same title.

RESULTS: Google Scholar produced records for ~95% of the papers cited by Chou et al. (n=476/506). A few of the 30 papers that were not in GS were later retrieved via PubMed and even regular Google Search. But due to its different structure, we could not run searches in GS that were originally performed by Chou et al. in PubMed, Web of Science, Scopus and PsycINFO®. Identifying 506 papers in GS was an inefficient process, especially for papers using similar search terms.

CONCLUSIONS: Has Google Scholar improved enough to be used alone in searching for systematic reviews? No. GS' constantly-changing content, algorithms and database structure make it a poor choice for systematic reviews. Looking for papers when you know their titles is a far different issue from discovering them initially. Further research is needed to determine when and how (and for what purposes) GS can be used alone. Google should provide details about GS' database coverage and improve its interface (e.g., with semantic search filters, stored searching, etc.). Perhaps then it will be an appropriate choice for systematic reviews.}, } @article {pmid23918551, year = {2013}, author = {Lien, MC and Jardin, E and Proctor, RW}, title = {An electrophysiological study of the object-based correspondence effect: is the effect triggered by an intended grasping action?.}, journal = {Attention, perception & psychophysics}, volume = {75}, number = {8}, pages = {1862-1882}, doi = {10.3758/s13414-013-0523-0}, pmid = {23918551}, issn = {1943-393X}, mesh = {Adolescent ; Adult ; Attention/*physiology ; Choice Behavior ; Discrimination, Psychological ; Electrophysiology ; Evoked Potentials/*physiology ; Female ; Functional Laterality ; Hand Strength/*physiology ; Humans ; Male ; Pattern Recognition, Visual/*physiology ; Psychomotor Performance/*physiology ; Reaction Time/*physiology ; Young Adult ; }, abstract = {We examined Goslin, Dixon, Fischer, Cangelosi, and Ellis's (Psychological Science 23:152-157, 2012) claim that the object-based correspondence effect (i.e., faster keypress responses when the orientation of an object's graspable part corresponds with the response location than when it does not) is the result of object-based attention (vision-action binding). In Experiment 1, participants determined the category of a centrally located object (kitchen utensil vs. tool), as in Goslin et al.'s study. The handle orientation (left vs. right) did or did not correspond with the response location (left vs. right). We found no correspondence effect on the response times (RTs) for either category. The effect was also not evident in the P1 and N1 components of the event-related potentials, which are thought to reflect the allocation of early visual attention. This finding was replicated in Experiment 2 for centrally located objects, even when the object was presented 45 times (33 more times than in Exp. 1). Critically, the correspondence effects on RTs, P1s, and N1s emerged only when the object was presented peripherally, so that the object handle was clearly located to the left or right of fixation. Experiment 3 provided further evidence that the effect was observed only for the base-centered objects, in which the handle was clearly positioned to the left or right of center. These findings contradict those of Goslin et al. and provide no evidence that an intended grasping action modulates visual attention. Instead, the findings support the spatial-coding account of the object-based correspondence effect.}, } @article {pmid23915090, year = {2013}, author = {Kellen, D and Klauer, KC and Singmann, H}, title = {On the measurement of criterion noise in signal detection theory: reply to Benjamin (2013).}, journal = {Psychological review}, volume = {120}, number = {3}, pages = {727-730}, doi = {10.1037/a0033141}, pmid = {23915090}, issn = {1939-1471}, mesh = {*Decision Making ; Humans ; *Models, Statistical ; *Psychological Theory ; *Recognition, Psychology ; *Signal Detection, Psychological ; }, abstract = {Kellen, Klauer, and Singmann (2012) questioned whether possible criterion noise would contribute significantly to modeling recognition memory. Our arguments were based on a reanalysis of the data by Benjamin, Diaz, and Wee (2009) as well as on new experimental data. In a comment, Benjamin (2013) questioned some of Kellen et al.'s conclusions and raised important issues regarding the new experimental data. In this reply, we revisit our arguments and provide new analyses in response to Benjamin's questions and issues.}, } @article {pmid23915089, year = {2013}, author = {Benjamin, AS}, title = {Where is the criterion noise in recognition? (Almost) everyplace you look: comment on Kellen, Klauer, and Singmann (2012).}, journal = {Psychological review}, volume = {120}, number = {3}, pages = {720-726}, pmid = {23915089}, issn = {1939-1471}, support = {R01 AG026263/AG/NIA NIH HHS/United States ; }, mesh = {*Decision Making ; Humans ; *Models, Statistical ; *Psychological Theory ; *Recognition, Psychology ; *Signal Detection, Psychological ; }, abstract = {Recent articles, including Benjamin, Diaz, and Wee (2009), have argued that recognition memory may be better understood if consideration is given to sources of noise in the decisions, as well as to those in the representations, underlying recognition judgments. They based that conclusion on a wide consideration of persisting mysteries in recognition research as well as a new experimental paradigm involving ensemble recognition. Kellen, Klauer, and Singmann (2012) reanalyzed Benjamin et al.'s data and introduced their own new experimental paradigm to this debate. They concluded that criteria do not vary much from trial to trial in recognition testing and, thus, that decision noise in recognition is small or nonexistent. However, their alternative interpretation of Benjamin et al.'s data relies on a questionable conclusion to reject all models in which the locations of criteria are restricted to be the same across ensembles and a meta-assumption that a model should be rejected as false if it yields unconventional parameters. In addition, their experimental logic relies on the assumption that ranking tasks are always bias-free. Here, I question these assumptions and suggest avenues for reconciliation between these contrasting claims.}, } @article {pmid23900961, year = {2014}, author = {Connors, NJ and Harnett, ZH and Hoffman, RS}, title = {Comparison of current recommended regimens of atropinization in organophosphate poisoning.}, journal = {Journal of medical toxicology : official journal of the American College of Medical Toxicology}, volume = {10}, number = {2}, pages = {143-147}, pmid = {23900961}, issn = {1937-6995}, mesh = {Antidotes/*administration & dosage/therapeutic use ; Atropine/*administration & dosage/therapeutic use ; Dose-Response Relationship, Drug ; Humans ; Kinetics ; Organophosphate Poisoning/*drug therapy ; *Practice Guidelines as Topic ; }, abstract = {Atropine is the mainstay of therapy in organophosphate (OP) toxicity, though research and consensus on dosing is lacking. In 2004, as reported by Eddleston et al. (J Toxicol Clin Toxicol 42(6):865-75, 2004), they noted variation in recommended regimens. We assessed revisions of original references, additional citations, and electronic sources to determine the current variability in atropine dosing recommendations. Updated editions of references from Eddleston et al.'s work, texts of Internal and Emergency Medicine, and electronic resources were reviewed for atropine dosing recommendations. For comparison, recommendations were assessed using the same mean dose (23.4 mg) and the highest dose (75 mg) of atropine as used in the original paper. Recommendations were also compared with the dosing regimen from the World Health Organization (WHO). Thirteen of the original recommendations were updated and 15 additional references were added giving a convenience sample of 28. Sufficient information to calculate time to targeted dose was provided by 24 of these samples. Compared to 2004, current recommendations have greatly increased the speed of atropinization with 13/24 able to reach the mean and high atropine dose within 30 min compared to 1/36 in 2004. In 2004, there were 13 regimens where the maximum time to reach 75 mg was over 18 h, whereas now, there are 2. While only one recommendation called for doubling the dose for faster escalation in 2004, 15 of the 24 current works include dose doubling. In 2004, Eddleston et al. called for an evidence-based guideline for the treatment of OP poisoning that could be disseminated worldwide. Many current recommendations can adequately treat patients within 1 h. While the WHO recommendations remain slow to treat patients with OP poisoning, other authorities are close to a consensus on rapid atropinization.}, } @article {pmid23893921, year = {2013}, author = {Sohns, M and Viktorova, E and Amos, CI and Brennan, P and Fehringer, G and Gaborieau, V and Han, Y and Heinrich, J and Chang-Claude, J and Hung, RJ and Müller-Nurasyid, M and Risch, A and Thomas, D and Bickeböller, H}, title = {Empirical hierarchical bayes approach to gene-environment interactions: development and application to genome-wide association studies of lung cancer in TRICL.}, journal = {Genetic epidemiology}, volume = {37}, number = {6}, pages = {551-559}, pmid = {23893921}, issn = {1098-2272}, support = {U19 CA148127/CA/NCI NIH HHS/United States ; P30 ES007048/ES/NIEHS NIH HHS/United States ; R01 ES019876/ES/NIEHS NIH HHS/United States ; P30 CA014089/CA/NCI NIH HHS/United States ; R01 CA141716/CA/NCI NIH HHS/United States ; 5U19CA148127-03/CA/NCI NIH HHS/United States ; }, mesh = {*Bayes Theorem ; Bias ; Case-Control Studies ; Computer Simulation ; *Gene-Environment Interaction ; Genome, Human ; Genome-Wide Association Study ; Humans ; Lung Neoplasms/*genetics ; *Models, Genetic ; Smoking ; }, abstract = {The analysis of gene-environment (G × E) interactions remains one of the greatest challenges in the postgenome-wide association studies (GWASs) era. Recent methods constitute a compromise between the robust but underpowered case-control and powerful case-only methods. Inferences of the latter are biased when the assumption of gene-environment (G-E) independence in controls fails. We propose a novel empirical hierarchical Bayes approach to G × E interaction (EHB-GE), which benefits from greater rank power while accounting for population-based G-E correlation. Building on Lewinger et al.'s ([2007] Genet Epidemiol 31:871-882) hierarchical Bayes prioritization approach, the method first obtains posterior G-E correlation estimates in controls for each marker, borrowing strength from G-E information across the genome. These posterior estimates are then subtracted from the corresponding case-only G × E estimates. We compared EHB-GE with rival methods using simulation. EHB-GE has similar or greater rank power to detect G × E interactions in the presence of large numbers of G-E correlations with weak to strong effects or only a low number of such correlations with large effect. When there are no or only a few weak G-E correlations, Murcray et al.'s method ([2009] Am J Epidemiol 169:219-226) identifies markers with low G × E interaction effects better. We applied EHB-GE and competing methods to four lung cancer case-control GWAS from the Interdisciplinary Research in Cancer of the Lung/International Lung Cancer Consortium with smoking as environmental factor. A number of genes worth investigating were identified by the EHB-GE approach.}, } @article {pmid23887818, year = {2014}, author = {Paxton, JM and Bruni, T and Greene, JD}, title = {Are 'counter-intuitive' deontological judgments really counter-intuitive? An empirical reply to.}, journal = {Social cognitive and affective neuroscience}, volume = {9}, number = {9}, pages = {1368-1371}, pmid = {23887818}, issn = {1749-5024}, mesh = {Adult ; Decision Making/*physiology ; Emotions/*physiology ; *Ethical Theory ; Female ; Humans ; Judgment/*physiology ; Male ; Middle Aged ; *Morals ; Neuropsychological Tests ; Photic Stimulation ; Reaction Time ; Young Adult ; }, abstract = {A substantial body of evidence indicates that utilitarian judgments (favoring the greater good) made in response to difficult moral dilemmas are preferentially supported by controlled, reflective processes, whereas deontological judgments (favoring rights/duties) in such cases are preferentially supported by automatic, intuitive processes. A recent neuroimaging study by Kahane et al. challenges this claim, using a new set of moral dilemmas that allegedly reverse the previously observed association. We report on a study in which we both induced and measured reflective responding to one of Greene et al.'s original dilemmas and one of Kahane et al.'s new dilemmas. For the original dilemma, induced reflection led to more utilitarian responding, replicating previous findings using the same methods. There was no overall effect of induced reflection for the new dilemma. However, for both dilemmas, the degree to which an individual engaged in prior reflection predicted the subsequent degree of utilitarian responding, with more reflective subjects providing more utilitarian judgments. These results cast doubt on Kahane et al.'s conclusions and buttress the original claim linking controlled, reflective processes to utilitarian judgment and automatic, intuitive processes to deontological judgment. Importantly, these results also speak to the generality of the underlying theory, indicating that what holds for cases involving utilitarian physical harms also holds for cases involving utilitarian lies.}, } @article {pmid23887085, year = {2013}, author = {Li, CT and Weng, CY and Lee, CC}, title = {An advanced temporal credential-based security scheme with mutual authentication and key agreement for wireless sensor networks.}, journal = {Sensors (Basel, Switzerland)}, volume = {13}, number = {8}, pages = {9589-9603}, pmid = {23887085}, issn = {1424-8220}, mesh = {*Algorithms ; Computer Communication Networks/*instrumentation ; Computer Security/*instrumentation ; Equipment Design ; Equipment Failure Analysis ; Information Storage and Retrieval/*methods ; Signal Processing, Computer-Assisted/*instrumentation ; *Transducers ; Wireless Technology/*instrumentation ; }, abstract = {Wireless sensor networks (WSNs) can be quickly and randomly deployed in any harsh and unattended environment and only authorized users are allowed to access reliable sensor nodes in WSNs with the aid of gateways (GWNs). Secure authentication models among the users, the sensor nodes and GWN are important research issues for ensuring communication security and data privacy in WSNs. In 2013, Xue et al. proposed a temporal-credential-based mutual authentication and key agreement scheme for WSNs. However, in this paper, we point out that Xue et al.'s scheme cannot resist stolen-verifier, insider, off-line password guessing, smart card lost problem and many logged-in users' attacks and these security weaknesses make the scheme inapplicable to practical WSN applications. To tackle these problems, we suggest a simple countermeasure to prevent proposed attacks while the other merits of Xue et al.'s authentication scheme are left unchanged.}, } @article {pmid23883763, year = {2013}, author = {Overgaard, S and Krueger, J}, title = {Social perception and "spectator theories" of other minds.}, journal = {The Behavioral and brain sciences}, volume = {36}, number = {4}, pages = {434-435}, doi = {10.1017/S0140525X12002014}, pmid = {23883763}, issn = {1469-1825}, mesh = {Cognition/*physiology ; Humans ; *Interpersonal Relations ; Mirror Neurons/*physiology ; *Social Perception ; Theory of Mind/*physiology ; }, abstract = {We resist Schilbach et al.'s characterization of the "social perception" approach to social cognition as a "spectator theory" of other minds. We show how the social perception view acknowledges the crucial role interaction plays in enabling social understanding. We also highlight a dilemma Schilbach et al. face in attempting to distinguish their second-person approach from the social perception view.}, } @article {pmid23883757, year = {2013}, author = {Lewis, C and Stack, J}, title = {A mature second-person neuroscience needs a first-person (plural) developmental foundation.}, journal = {The Behavioral and brain sciences}, volume = {36}, number = {4}, pages = {428-429}, doi = {10.1017/S0140525X12001963}, pmid = {23883757}, issn = {1469-1825}, mesh = {Cognition/*physiology ; Humans ; *Interpersonal Relations ; Mirror Neurons/*physiology ; *Social Perception ; Theory of Mind/*physiology ; }, abstract = {Schilbach et al.'s model assumes that the ability to "experience" minds is already present in human infants and therefore falls foul of the very intellectualist problems it attempts to avoid. We propose an alternative relational, action-based account, which attempts to grasp how the individual's construction of knowledge develops within interactions.}, } @article {pmid23883748, year = {2013}, author = {Evans, N}, title = {On projecting grammatical persons into social neurocognition: a view from linguistics.}, journal = {The Behavioral and brain sciences}, volume = {36}, number = {4}, pages = {419-420}, doi = {10.1017/S0140525X12001896}, pmid = {23883748}, issn = {1469-1825}, mesh = {Cognition/*physiology ; Humans ; *Interpersonal Relations ; Mirror Neurons/*physiology ; *Social Perception ; Theory of Mind/*physiology ; }, abstract = {Though it draws on the grammatical metaphor of person (first, third, second) in terms of representations, Schilbach et al.'s target article does not consider an orthogonal line of evidence for the centrality of interaction to social cognition: the many grammatical phenomena, some widespread cross-linguistically and some only being discovered, which are geared to supporting real-time interaction. My commentary reviews these, and the contribution linguistic evidence can make to a fuller account of social cognition.}, } @article {pmid23881759, year = {2013}, author = {Daggett, VS and Bakas, T and Buelow, J and Habermann, B and Murray, LL}, title = {Needs and concerns of male combat Veterans with mild traumatic brain injury.}, journal = {Journal of rehabilitation research and development}, volume = {50}, number = {3}, pages = {327-340}, doi = {10.1682/jrrd.2011.09.0168}, pmid = {23881759}, issn = {1938-1352}, mesh = {*Adaptation, Psychological ; Adult ; Afghan Campaign 2001- ; Behavior ; Brain Injuries/complications/*psychology/*rehabilitation ; *Emotions ; Employment/psychology ; Fatigue/etiology ; Headache/etiology ; Humans ; Interpersonal Relations ; Interviews as Topic ; Iraq War, 2003-2011 ; Male ; Memory Disorders/etiology/psychology ; Models, Theoretical ; Needs Assessment ; Sleep Disorders, Intrinsic/etiology ; Social Participation/psychology ; Social Support ; Tinnitus/etiology ; Veterans/*psychology ; Warfare ; Young Adult ; }, abstract = {Traumatic brain injury (TBI) has emerged as a major cause of morbidity among U.S. servicemembers who have served in Iraq and Afghanistan. Even mild TBI (mTBI) can result in cognitive impairments that can affect the community reintegration of Veterans postdeployment. The purpose of this study was to explore the needs and concerns of combat Veterans with mTBI to provide support for an mTBI-specific conceptual model (Conceptual Model in the Context of mTBI) derived from Ferrans et al.'s health-related quality of life model and the TBI literature. Content analysis of qualitative interview data was conducted using a thematic matrix with a predetermined code list. Data saturation was achieved after interviews with eight male Veterans. Six key categories and predominant themes emerged: cognitive impairments, physical symptoms, emotions and behaviors, instrumental activities of daily living, interpersonal interactions, and community reintegration. Findings provide preliminary support for a new, context-specific conceptual model that has the potential to identify areas for future interventions to enhance community reintegration of combat Veterans with mTBI.}, } @article {pmid23861012, year = {2015}, author = {Ejova, A and Delfabbro, PH and Navarro, DJ}, title = {Erroneous gambling-related beliefs as illusions of primary and secondary control: a confirmatory factor analysis.}, journal = {Journal of gambling studies}, volume = {31}, number = {1}, pages = {133-160}, pmid = {23861012}, issn = {1573-3602}, mesh = {Adolescent ; Adult ; Australia ; Behavior, Addictive/*psychology ; Factor Analysis, Statistical ; Female ; Gambling/*psychology ; Humans ; Illusions/*psychology ; *Internal-External Control ; Male ; *Risk-Taking ; }, abstract = {Different classification systems for erroneous beliefs about gambling have been proposed, consistently alluding to 'illusion of control' and 'gambler's fallacy' categories. None of these classification systems have, however, considered the how the illusion of control and the gambler's fallacy might be interrelated. In this paper, we report the findings of a confirmatory factor analysis that examines the proposal that most erroneous gambling-related beliefs can be defined in terms of Rothbaum et al.'s (J Pers Soc Psychol, doi: 10.1037/0022-3514.42.1.5 , 1982) distinction between 'primary' and 'secondary' illusory control, with the former being driven to a large extent by the well-known gambler's fallacy and the latter being driven by a complex of beliefs about supernatural forces such as God and luck. A survey consisting of 100 items derived from existing instruments was administered to 329 participants. The analysis confirmed the existence of two latent structures (beliefs in primary and secondary control), while also offering support to the idea that gambler's fallacy-style reasoning may underlie both perceived primary control and beliefs about the cyclical nature of luck, a form of perceived secondary control. The results suggest the need for a greater focus on the role of underlying processes or belief structures as factors that foster susceptibility to specific beliefs in gambling situations. Addressing and recognising the importance of these underlying factors may also have implications for cognitive therapy treatments for problem gambling.}, } @article {pmid23855322, year = {2014}, author = {Phillips, TR and Sellbom, M and Ben-Porath, YS and Patrick, CJ}, title = {Further development and construct validation of MMPI-2-RF indices of global psychopathy, fearless-dominance, and impulsive-antisociality in a sample of incarcerated women.}, journal = {Law and human behavior}, volume = {38}, number = {1}, pages = {34-46}, doi = {10.1037/lhb0000040}, pmid = {23855322}, issn = {1573-661X}, mesh = {Adolescent ; Adult ; Antisocial Personality Disorder/*diagnosis/*psychology ; Disruptive, Impulse Control, and Conduct Disorders/*diagnosis/*psychology ; Fear ; Female ; Humans ; MMPI/*statistics & numerical data ; Male ; Middle Aged ; Narcissism ; Prisoners/*psychology ; Psychometrics/statistics & numerical data ; Reference Values ; Reproducibility of Results ; Sex Factors ; Statistics as Topic ; Young Adult ; }, abstract = {Replicating and extending research by Sellbom et al. (M. Sellbom, Y. S. Ben-Porath, C. J. Patrick, D. B. Wygant, D. M. Gartland, & K. P. Stafford, 2012, Development and Construct Validation of the MMPI-2-RF Measures of Global Psychopathy, Fearless-Dominance, and Impulsive-Antisociality, Personality Disorders: Theory, Research, and Treatment, 3, 17-38), the current study examined the criterion-related validity of three self-report indices of psychopathy that were derived from scores on the Minnesota Multiphasic Personality Inventory (MMPI)-2-Restructured Form (MMPI-2-RF; Y. S. Ben-Porath & A. Tellegen, 2008, Minnesota Multiphasic Personality Inventory-2-Restructured Form: Manual for Administration, Scoring, and Interpretation, Minneapolis, MN: University of Minnesota Press). We estimated psychopathy indices by regressing scores from the Psychopathic Personality Inventory (PPI; S. O. Lilienfeld & B. P. Andrews, 1996, Development and Preliminary Validation of a Self-Report Measure of Psychopathic Personality Traits in Noncriminal Populations, Journal of Personality Assessment, 66, 488-524) and its two distinct facets, Fearless-Dominance and Impulsive-Antisociality, onto conceptually selected MMPI-2-RF scales. Data for a newly collected sample of 230 incarcerated women were combined with existing data from Sellbom et al.'s (2012) male correctional and mixed-gender college samples to establish regression equations with optimal generalizability. Correlation and regression analyses were then used to examine associations between the MMPI-2-RF-based estimates of PPI psychopathy and criterion measures (i.e., other well-established measures of psychopathy and conceptually related personality traits), and to evaluate whether gender moderated these associations. The MMPI-2-RF-based psychopathy indices correlated as expected with criterion measures and showed only one significant moderating effect for gender, namely, in the association between psychopathy and narcissism. These results provide further support for the validity of the MMPI-2-RF-based estimates of PPI psychopathy, and encourage their use in research and clinical contexts.}, } @article {pmid23838749, year = {2013}, author = {Ahrens, J and Amselem, E and Cabello, A and Bourennane, M}, title = {Two fundamental experimental tests of nonclassicality with qutrits.}, journal = {Scientific reports}, volume = {3}, number = {}, pages = {2170}, pmid = {23838749}, issn = {2045-2322}, abstract = {We report two fundamental experiments on three-level quantum systems (qutrits). The first one tests the simplest task for which quantum mechanics provides an advantage with respect to classical physics. The quantum advantage is certified by the violation of Wright's inequality, the simplest classical inequality violated by quantum mechanics. In the second experiment, we obtain contextual correlations by sequentially measuring pairs of compatible observables on a qutrit, and show the violation of Klyachko et al.'s inequality, the most fundamental noncontextuality inequality violated by qutrits. Our experiment tests exactly Klyachko et al.'s inequality, uses the same measurement procedure for each observable in every context, and implements the sequential measurements in any possible order.}, } @article {pmid23836550, year = {2013}, author = {Cage, E and Pellicano, E and Shah, P and Bird, G}, title = {Reputation management: evidence for ability but reduced propensity in autism.}, journal = {Autism research : official journal of the International Society for Autism Research}, volume = {6}, number = {5}, pages = {433-442}, doi = {10.1002/aur.1313}, pmid = {23836550}, issn = {1939-3806}, mesh = {Adult ; Altruism ; *Aptitude ; Child Development Disorders, Pervasive/*diagnosis/*psychology ; *Emotional Intelligence ; Humans ; *Interpersonal Relations ; Male ; *Motivation ; *Self Concept ; *Social Facilitation ; *Theory of Mind ; Young Adult ; }, abstract = {Previous research has reported that autistic adults do not manage their reputation, purportedly due to problems with theory of mind [Izuma, Matsumoto, Camerer, & Adolphs]. The current study aimed to test alternative explanations for this apparent lack of reputation management. Twenty typical and 19 autistic adults donated to charity and to a person, both when alone and when observed. In an additional manipulation, for half of the participants, the observer was also the recipient of their donations, and participants were told that this observer would subsequently have the opportunity to donate to them (motivation condition). This manipulation was designed to encourage an expectation of a reciprocal "tit-for-tat" strategy in the participant, which may motivate participants to change their behavior to receive more donations. The remaining participants were told that the person watching was just observing the procedure (no motivation condition). Our results replicated Izuma et al.'s finding that autistic adults did not donate more to charity when observed. Yet, in the motivation condition, both typical and autistic adults donated significantly more to the observer when watched, although this effect was significantly attenuated in autistic individuals. Results indicate that, while individuals with autism may have the ability to think about reputation, a reduced expectation of reciprocal behavior from others may reduce the degree to which they engage in reputation management.}, } @article {pmid23835891, year = {2013}, author = {Qureshi, R and Pacquiao, DF}, title = {Ethnographic study of experiences of Pakistani women immigrants with pregnancy, birthing, and postpartum care in the United States and Pakistan.}, journal = {Journal of transcultural nursing : official journal of the Transcultural Nursing Society}, volume = {24}, number = {4}, pages = {355-362}, doi = {10.1177/1043659613493438}, pmid = {23835891}, issn = {1552-7832}, mesh = {Adult ; Anthropology, Cultural ; *Delivery, Obstetric ; Emigrants and Immigrants/*psychology ; Female ; Health Knowledge, Attitudes, Practice/ethnology ; Humans ; *Maternal Health Services ; Pakistan/ethnology ; Pregnancy ; Pregnancy Complications/*ethnology ; Social Adjustment ; United States ; }, abstract = {STUDY PURPOSE: Describe the comparative birthing experiences of Pakistani immigrant women in Pakistan and the United States.

CONCEPTUAL FRAMEWORK: The framework was drawn from Berry's cultural adaptation, Glick-Schiller et al.'s transnationalism and Berkman's social network.

METHODOLOGY: Qualitative

DESIGN: Women experienced difficulties associated with inability to observe cultural traditions and loss of extended, gendered kin support. Adaptive strategies were evident through development of social networks of weak ties with non-kin groups in the United States, maintenance of transnational ties with kin back in Pakistan, and assimilation of less gender-defined roles by women and their spouses.}, } @article {pmid23835090, year = {2013}, author = {Mitosek-Szewczyk, K and Tabarkiewicz, J and Wilczynska, B and Lobejko, K and Berbecki, J and Nastaj, M and Dworzanska, E and Kolodziejczyk, B and Stelmasiak, Z and Rolinski, J}, title = {Impact of cladribine therapy on changes in circulating dendritic cell subsets, T cells and B cells in patients with multiple sclerosis.}, journal = {Journal of the neurological sciences}, volume = {332}, number = {1-2}, pages = {35-40}, doi = {10.1016/j.jns.2013.06.003}, pmid = {23835090}, issn = {1878-5883}, mesh = {Adult ; Analysis of Variance ; Antigens, CD/metabolism ; B-Lymphocytes/*drug effects ; Cladribine/*pharmacology/therapeutic use ; Dendritic Cells/*drug effects ; Female ; Flow Cytometry ; Humans ; Immunosuppressive Agents/*pharmacology/therapeutic use ; Male ; Middle Aged ; Multiple Sclerosis/drug therapy/immunology/*pathology ; T-Lymphocytes/*drug effects ; }, abstract = {BACKGROUND: Cladribine causes sustained reduction in peripheral T and B cell populations while sparing other immune cells. We determined two populations of dendritic cells (DCs): namely CD1c(+)/CD19(-) (myeloid DCs) and CD303(+)/CD123(+) (plasmacytoid DCs), CD19(+) B lymphocytes, CD3(+) T lymphocytes and CD4(+) or CD8(+) subpopulations in patients with multiple sclerosis after cladribine therapy.

METHODS: We examined 50 patients with secondary progressive multiple sclerosis (SP MS) according to McDonalds et al.'s criteria, 2001 [15]. Blood samples were collected before the initiation of cladribine therapy and after 1st, 2nd, 3th, 4th and 5th courses of treatment. DC subsets, T and B cells were analyzed by flow cytometry.

RESULTS: During cladribine treatment the myeloid DCs CD1c(+)/CD19(-) did not change (p=0.73175), and the plasmacytoid DCs CD303(+)/CD123(+) significantly increased (p=0.00034) which resulted in significant changes in the ratio of myeloid DCs to plasmacytoid DCs (p=0.00273). During therapy, B lymphocyte CD19(+) significantly decreased (p=0.00005) and significant changes in CD4(+) cells (p=0.00191), changes in CD8(+) cells (p=0.05760) and significant changes in CD3(+) (p=0.01822) were found.

CONCLUSIONS: We noticed significant trend to increase the CD303(+) circulating the dendritic cells. This population produces large amounts of IFN-alfa. We found significant and rapid decrease in B cells and CD4(+) Th cells. Our results suggest two possible ways of beneficial cladribine influence on immune system in MS. Induction of IFN-alfa producing cells and their predominance over BDCA-1(+) DCs, which are associated with cytotoxic response. Additionally, cladribine could influence two populations of lymphocytes: B cells and Th lymphocytes responsible for induction of immune response against myelin antigens.}, } @article {pmid23832955, year = {2014}, author = {Levant, RF and Wimer, DJ}, title = {Masculinity constructs as protective buffers and risk factors for men's health.}, journal = {American journal of men's health}, volume = {8}, number = {2}, pages = {110-120}, doi = {10.1177/1557988313494408}, pmid = {23832955}, issn = {1557-9891}, mesh = {Adolescent ; Adult ; *Health Behavior/ethnology ; Humans ; Male ; *Masculinity ; *Men's Health/ethnology ; Middle Aged ; Models, Statistical ; Reproducibility of Results ; Risk Factors ; Surveys and Questionnaires ; United States ; Young Adult ; }, abstract = {This study was designed to replicate the study of Levant, Wimer, and Williams (2011), which reported complex relationships between masculinity and health behaviors using a more diverse sample and updated measures. A sample of 589 college and community-dwelling men responded to an online survey consisting of five scales. Levant et al.'s (2011) study was partially replicated-some masculinity constructs were identified as protective buffers for some health behaviors and others as risk factors. The vast majority of the findings that were replicated were risk factors, suggesting that traditional masculinity is more of risk than a buffer, and occurred in the analyses involving Avoiding Anger and Stress and Avoiding Substance Use subscales, suggesting that these health behaviors are most closely associated with masculinity. The results are discussed in terms of limitations, suggestions for future research, and implications for health care practice.}, } @article {pmid23828650, year = {2013}, author = {Khan, MK and Kumari, S}, title = {An authentication scheme for secure access to healthcare services.}, journal = {Journal of medical systems}, volume = {37}, number = {4}, pages = {9954}, pmid = {23828650}, issn = {1573-689X}, mesh = {Algorithms ; *Computer Security ; *Confidentiality ; Health Services ; Humans ; Information Systems ; Telemedicine ; Theft ; }, abstract = {Last few decades have witnessed boom in the development of information and communication technologies. Health-sector has also been benefitted with this advancement. To ensure secure access to healthcare services some user authentication mechanisms have been proposed. In 2012, Wei et al. proposed a user authentication scheme for telecare medical information system (TMIS). Recently, Zhu pointed out offline password guessing attack on Wei et al.'s scheme and proposed an improved scheme. In this article, we analyze both of these schemes for their effectiveness in TMIS. We show that Wei et al.'s scheme and its improvement proposed by Zhu fail to achieve some important characteristics necessary for secure user authentication. We find that security problems of Wei et al.'s scheme stick with Zhu's scheme; like undetectable online password guessing attack, inefficacy of password change phase, traceability of user's stolen/lost smart card and denial-of-service threat. We also identify that Wei et al.'s scheme lacks forward secrecy and Zhu's scheme lacks session key between user and healthcare server. We therefore propose an authentication scheme for TMIS with forward secrecy which preserves the confidentiality of air messages even if master secret key of healthcare server is compromised. Our scheme retains advantages of Wei et al.'s scheme and Zhu's scheme, and offers additional security. The security analysis and comparison results show the enhanced suitability of our scheme for TMIS.}, } @article {pmid23824837, year = {2014}, author = {Lee, CK and Chung, N and Bernhard, BJ}, title = {Examining the structural relationships among gambling motivation, passion, and consequences of internet sports betting.}, journal = {Journal of gambling studies}, volume = {30}, number = {4}, pages = {845-858}, pmid = {23824837}, issn = {1573-3602}, mesh = {Behavior, Addictive/epidemiology/*psychology ; Female ; Gambling/epidemiology/*psychology ; Humans ; Internet/*statistics & numerical data ; Male ; Motivation ; Republic of Korea/epidemiology ; *Self Concept ; Social Adjustment ; *Sports ; Young Adult ; }, abstract = {The rise in popularity of Internet gambling has led to new gambling controversies among researchers and policymakers alike. Opponents frequently point to the negative impacts of problem gambling, while advocates tend to view this form of gambling as relatively harmless and convenient entertainment for the vast majority of participants. Interestingly, in making their points, both sides cite empirical arguments about passion for the gambling act-with opponents arguing that Internet gambling enables unhealthy obsessions, and advocates pointing to the apparent intensive interest of large numbers of Internet players. As it turns out, both sides may have a point. In this paper, we examine whether types of passion were related to types of motivation and consequences. The data were collected through a sample from an online gambling website in South Korea. We rely upon Rousseau et al.'s (J Gambl Stud 18(1):45-66, 2002) seminal work on positive and negative aspects of passion, and in the process we develop a framework for understanding positive and negative consequences of this form of gambling. The results reveal that intrinsic gambling motivations (e.g., gambling for excitement) is related to harmonious passion, which in turn results in positive consequences. Meanwhile, extrinsic gambling motivations (e.g., money) is related to obsessive passion, which in turn results in negative consequences.}, } @article {pmid23818249, year = {2013}, author = {Wu, F and Xu, L}, title = {Security analysis and improvement of a privacy authentication scheme for telecare medical information systems.}, journal = {Journal of medical systems}, volume = {37}, number = {4}, pages = {9958}, pmid = {23818249}, issn = {1573-689X}, mesh = {*Computer Security ; Confidentiality ; Health Information Exchange ; Humans ; Information Systems ; *Privacy ; Telemedicine ; }, abstract = {Nowadays, patients can gain many kinds of medical service on line via Telecare Medical Information Systems(TMIS) due to the fast development of computer technology. So security of communication through network between the users and the server is very significant. Authentication plays an important part to protect information from being attacked by malicious attackers. Recently, Jiang et al. proposed a privacy enhanced scheme for TMIS using smart cards and claimed their scheme was better than Chen et al.'s. However, we have showed that Jiang et al.'s scheme has the weakness of ID uselessness and is vulnerable to off-line password guessing attack and user impersonation attack if an attacker compromises the legal user's smart card. Also, it can't resist DoS attack in two cases: after a successful impersonation attack and wrong password input in Password change phase. Then we propose an improved mutual authentication scheme used for a telecare medical information system. Remote monitoring, checking patients' past medical history record and medical consultant can be applied in the system where information transmits via Internet. Finally, our analysis indicates that the suggested scheme overcomes the disadvantages of Jiang et al.'s scheme and is practical for TMIS.}, } @article {pmid23803353, year = {2013}, author = {Taylor, L and Beard, P and Law, S}, title = {The Ebb and FLO of improving patient safety.}, journal = {HealthcarePapers}, volume = {13}, number = {1}, pages = {42-7; discussion 78-82}, doi = {10.12927/hcpap.2013.23342}, pmid = {23803353}, issn = {1488-917X}, mesh = {Cross Infection/*prevention & control ; Health Personnel/*standards ; Humans ; Infection Control/*standards ; Patient Safety/*standards ; Safety Management/*standards ; }, abstract = {Patient safety in Canada has improved. Yet, dramatic transformation in safety across the continuum of care remains elusive. Front-line ownership (FLO) as outlined by Zimmerman and colleagues represents a novel bottom-up, or "discovery," approach to surmounting the challenges of further improving patient safety. Zimmerman et al.'s rationale and pilot study results suggest, however, that answers to important questions are required prior to the general adoption of FLO. For instance, in FLO's front-line collaborations, what is senior leadership's role? Is it limited to support, or is there a critical role in setting priorities and networking outside organizational boundaries to avoid reinventing the wheel? Who is included in the FLO team? Are housekeepers, doctors and patients all key teammates and contributors to success? In the near term, health organizations' support for FLO should be balanced with more directive safety solutions, within a broad framework that values both evidence-based practice and the generation of practice-based evidence. In this context, the authors of this commentary probe particular dimensions of FLO's theory and practice to promote the best positioning of FLO to enhance its optimal application of knowledge to reduce harm and improve patient safety.}, } @article {pmid23792806, year = {2013}, author = {Hall, ML and Mayberry, RI and Ferreira, VS}, title = {Cognitive constraints on constituent order: evidence from elicited pantomime.}, journal = {Cognition}, volume = {129}, number = {1}, pages = {1-17}, pmid = {23792806}, issn = {1873-7838}, support = {R01 HD051030/HD/NICHD NIH HHS/United States ; T32 DC000041/DC/NIDCD NIH HHS/United States ; HD051030/HD/NICHD NIH HHS/United States ; 5T32DC000041-19/DC/NIDCD NIH HHS/United States ; }, mesh = {Adult ; Cognition/*physiology ; *Gestures ; Humans ; *Language ; Qualitative Research ; Sign Language ; Young Adult ; }, abstract = {To what extent does human cognition influence the structure of human language? Recent experiments using elicited pantomime suggest that the prevalence of Subject-Object-Verb (SOV) order across the world's languages may arise in part because SOV order is most compatible with how we conceptually represent transitive events (Goldin-Meadow, So, Özyürek, & Mylander, 2008). However, this raises the question as to why non-SOV orders exist. Two recent studies (Meir, Lifshitz, Ilkbasaran, & Padden, 2010; Gibson et al., 2013) suggest that SOV might be suboptimal for describing events in which both the agent and patient are plausible agents (e.g. a woman pushing a boy); we call these "reversible" events. We replicate these findings using elicited pantomime and offer a new interpretation. Meir et al.'s (2010) account is framed largely in terms of constraints on comprehension, while Gibson et al.'s (2013) account involves minimizing the risk of information loss or memory degradation. We offer an alternative hypothesis that is grounded in constraints on production. We consider the implications of these findings for the distribution of constituent order in the world's spoken languages and for the structure of emerging sign languages.}, } @article {pmid23780402, year = {2013}, author = {Udayakumaran, S and Panikar, D and Mathew, J}, title = {Reply to Dr. Henderson et al.'s comments.}, journal = {Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery}, volume = {29}, number = {8}, pages = {1225}, pmid = {23780402}, issn = {1433-0350}, mesh = {Ectodermal Dysplasia/*surgery ; Exsanguination/*surgery ; Female ; Humans ; Limb Deformities, Congenital/*surgery ; Scalp Dermatoses/*congenital ; *Skin Transplantation ; Staphylococcal Skin Infections/*surgery ; }, } @article {pmid23777515, year = {2013}, author = {Güler, M}, title = {An investigation of the stochastic Hodgkin-Huxley models under noisy rate functions.}, journal = {Neural computation}, volume = {25}, number = {9}, pages = {2355-2372}, doi = {10.1162/NECO_a_00487}, pmid = {23777515}, issn = {1530-888X}, mesh = {Action Potentials/*physiology ; Algorithms ; Animals ; Cell Membrane/metabolism ; Humans ; Ion Channel Gating/*physiology ; Ion Channels/*physiology ; }, abstract = {The effects of ion channel fluctuations on the transmembrane voltage activity are potentially profound in small-size excitable membrane patches. Different groups have extended Hodgkin-Huxley equations into stochastic differential equations to capture the effects of ion channel noise analytically (Fox & Lu, 1994; Linaro, Storace, & Giugliano, 2011; Güler, 2013). Studies have shown that the accuracy of spiking statistics by Fox and Lu's model does not match well with the corresponding statistics from the exact microscopic simulations. The models of both Linaro et al. and Güler, however, were found to produce highly accurate statistics. Here we extend the examination of these models to the case in which the rate functions for the opening and closing of gates are under the influence of noise. For that purpose, the usual rate functions are accompanied additively by Ornstein-Uhlenbeck-type stochastic angular variables. Moreover, we argue that the existence of such noise in the rate functions is a plausible physiological phenomenon for finite-size membranes. It is observed that the presence of noise in the rates is not effective on the degree of inaccuracies within the Fox and Lu model. Güler model's accuracy is found to remain high as in the case of noise free rates. But the performance of Linaro et al.'s model is seen to degrade seriously with the increasing strength of the introduced rate function noise. We attribute this failure of Linaro et al.'s model to the use of the covariance function of open channels at the steady state, in its derivation.}, } @article {pmid23759278, year = {2013}, author = {Zimmerman, M and Martinez, JH and Young, D and Chelminski, I and Dalrymple, K}, title = {Severity classification on the Hamilton Depression Rating Scale.}, journal = {Journal of affective disorders}, volume = {150}, number = {2}, pages = {384-388}, doi = {10.1016/j.jad.2013.04.028}, pmid = {23759278}, issn = {1573-2517}, mesh = {Adolescent ; Adult ; Aged ; Depressive Disorder, Major/classification/*diagnosis/psychology ; Female ; Humans ; Male ; Middle Aged ; Outpatients ; *Psychiatric Status Rating Scales ; Sensitivity and Specificity ; Severity of Illness Index ; Young Adult ; }, abstract = {BACKGROUND: Symptom severity as a moderator of treatment response has been the subject of debate over the past 20 years. Each of the meta- and mega-analyses examining the treatment significance of depression severity used the Hamilton Depression Rating Scale (HAMD), wholly, or in part, to define severity, though the cutoff used to define severe depression varied. There is limited empirical research establishing cutoff scores for bands of severity on the HAMD. The goal of the study is to empirically establish cutoff scores on the HAMD in their allocation of patients to severity groups.

METHODS: Six hundred twenty-seven outpatients with current major depressive disorder were evaluated with a semi-structured diagnostic interview. Scores on the 17-item HAMD were derived from ratings according to the conversion method described by Endicott et al. (1981). The patients were also rated on the Clinical Global Index of Severity (CGI). Receiver operating curves were computed to identify the cutoff that optimally discriminated between patients with mild vs. moderate and moderate vs. severe depression.

RESULTS: HAMD scores were significantly lower in patients with mild depression than patients with moderate depression, and patients with moderate depression scored significantly lower than patients with severe depression. The cutoff score on the HAMD that maximized the sum of sensitivity and specificity was 17 for the comparison of mild vs. moderate depression and 24 for the comparison of moderate vs. severe depression.

LIMITATIONS: The present study was conducted in a single outpatient practice in which the majority of patients were white, female, and had health insurance. Although the study was limited to a single site, a strength of the recruitment procedure was that the sample was not selected for participation in a treatment study, and exclusion and inclusion criteria did not reduce the representativeness of the patient groups. The analyses were based on HAMD scores extracted from ratings on the SADS. However, we used Endicott et al.'s (1981) empirically established formula for deriving a HAMD score from SADS ratings, and our results concurred with other small studies of the mean and median HAMD scores in severity groups.

CONCLUSIONS: Based on this large study of psychiatric outpatients with major depressive disorder we recommend the following severity ranges for the HAMD: no depression (0-7); mild depression (8-16); moderate depression (17-23); and severe depression (≥24).}, } @article {pmid23757469, year = {2013}, author = {Mihara, T and Tojo, K and Uchimoto, K and Morita, S and Goto, T}, title = {Reevaluation of the effectiveness of ramosetron for preventing postoperative nausea and vomiting: a systematic review and meta-analysis.}, journal = {Anesthesia and analgesia}, volume = {117}, number = {2}, pages = {329-339}, doi = {10.1213/ANE.0b013e31829847a1}, pmid = {23757469}, issn = {1526-7598}, mesh = {Adult ; Aged ; Aged, 80 and over ; Antiemetics/adverse effects/*therapeutic use ; Benzimidazoles/adverse effects/*therapeutic use ; Female ; Humans ; Male ; Middle Aged ; Odds Ratio ; Ondansetron/therapeutic use ; Postoperative Nausea and Vomiting/*prevention & control ; Randomized Controlled Trials as Topic ; Time Factors ; Treatment Outcome ; Young Adult ; }, abstract = {BACKGROUND: Ramosetron has been shown to have a very strong effect for preventing postoperative nausea and vomiting (PONV) in previous meta-analyses. However, these previous meta-analyses included a number of studies by Fujii et al. which have now been proven to have been fabricated. In the present meta-analysis, we reevaluated the effectiveness of ramosetron in preventing PONV after excluding Fujii et al.'s randomized controlled trials.

METHODS: We searched MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), Embase, and Web of Science. All double-blind randomized controlled trials that tested the efficacy of ramosetron compared with a placebo or other drugs as a control in the prophylaxis of PONV were considered to be eligible. The first postoperative 24 hours were divided into early (0-6 hours) and late (6-24 hours) time periods, and we collected these data separately.

RESULTS: A total of 1372 patients were included in the final analysis. Compared with a placebo, ramosetron reduced the incidence of early postoperative nausea (PON) (relative risk [RR] [95% confidence interval] 0.59 [0.47-0.73]: number needed to treat [NNT] [95% confidence interval] 6.0 [4.3-9.7]), late PON (RR 0.65 [0.49-0.85]: NNT 7.2 [4.6-16.6]), early postoperative vomiting (POV) (RR 0.48 [0.31-0.74]: NNT 14.8 [8.3-70.4]), and late POV (RR 0.50 [0.35-0.73]: NNT 12.3 [7.1-47.6]). Compared with ondansetron, ramosetron reduces early POV (RR 0.50 [0.28-0.90]: NNT 24.1 [10.7-98.0]) and late POV (RR 0.53 [0.34-0.81]: NNT 27.2 [12.0-102.0]) but not PON.

CONCLUSIONS: Ramosetron has a significant effect for preventing PONV compared with a placebo, but less than that reported in previous analyses. Ramosetron also has statistically significant differences in preventing early and late POV compared with ondansetron, but the clinical significance may be questioned because the NNTs are large.}, } @article {pmid23755107, year = {2014}, author = {Del Re, AC and Spielmans, GI and Flückiger, C and Wampold, BE}, title = {Efficacy of new generation antidepressants: differences seem illusory.}, journal = {PloS one}, volume = {8}, number = {6}, pages = {e63509}, pmid = {23755107}, issn = {1932-6203}, mesh = {Antidepressive Agents, Second-Generation/*therapeutic use ; Computer Simulation ; Humans ; Illusions ; Probability ; Treatment Outcome ; }, abstract = {BACKGROUND: Recently, Cipriani and colleagues examined the relative efficacy of 12 new-generation antidepressants on major depression using network meta-analytic methods. They found that some of these medications outperformed others in patient response to treatment. However, several methodological criticisms have been raised about network meta-analysis and Cipriani's analysis in particular which creates the concern that the stated superiority of some antidepressants relative to others may be unwarranted.

MATERIALS AND METHODS: A Monte Carlo simulation was conducted which involved replicating Cipriani's network meta-analysis under the null hypothesis (i.e., no true differences between antidepressants). The following simulation strategy was implemented: (1) 1000 simulations were generated under the null hypothesis (i.e., under the assumption that there were no differences among the 12 antidepressants), (2) each of the 1000 simulations were network meta-analyzed, and (3) the total number of false positive results from the network meta-analyses were calculated.

FINDINGS: Greater than 7 times out of 10, the network meta-analysis resulted in one or more comparisons that indicated the superiority of at least one antidepressant when no such true differences among them existed.

INTERPRETATION: Based on our simulation study, the results indicated that under identical conditions to those of the 117 RCTs with 236 treatment arms contained in Cipriani et al.'s meta-analysis, one or more false claims about the relative efficacy of antidepressants will be made over 70% of the time. As others have shown as well, there is little evidence in these trials that any antidepressant is more effective than another. The tendency of network meta-analyses to generate false positive results should be considered when conducting multiple comparison analyses.}, } @article {pmid23747652, year = {2013}, author = {Rips, LJ and Asmuth, J and Bloomfield, A}, title = {Can statistical learning bootstrap the integers?.}, journal = {Cognition}, volume = {128}, number = {3}, pages = {320-330}, doi = {10.1016/j.cognition.2013.04.001}, pmid = {23747652}, issn = {1873-7838}, mesh = {Child ; Humans ; Knowledge ; Language ; *Learning ; *Models, Psychological ; }, abstract = {This paper examines Piantadosi, Tenenbaum, and Goodman's (2012) model for how children learn the relation between number words ("one" through "ten") and cardinalities (sizes of sets with one through ten elements). This model shows how statistical learning can induce this relation, reorganizing its procedures as it does so in roughly the way children do. We question, however, Piantadosi et al.'s claim that the model performs "Quinian bootstrapping," in the sense of Carey (2009). Unlike bootstrapping, the concept it learns is not discontinuous with the concepts it starts with. Instead, the model learns by recombining its primitives into hypotheses and confirming them statistically. As such, it accords better with earlier claims (Fodor, 1975, 1981) that learning does not increase expressive power. We also question the relevance of the simulation for children's learning. The model starts with a preselected set of15 primitives, and the procedure it learns differs from children's method. Finally, the partial knowledge of the positive integers that the model attains is consistent with an infinite number of nonstandard meanings-for example, that the integers stop after ten or loop from ten back to one.}, } @article {pmid23747038, year = {2013}, author = {Liang, BA and Mackey, TK and Lovett, KM}, title = {Reply to Stanback et al.'s "Suspect online sellers and contraceptive access".}, journal = {Contraception}, volume = {88}, number = {4}, pages = {583}, doi = {10.1016/j.contraception.2013.03.013}, pmid = {23747038}, issn = {1879-0518}, mesh = {Contraceptive Agents, Female/*supply & distribution ; Female ; Humans ; *Pharmaceutical Services, Online ; }, } @article {pmid23740000, year = {2013}, author = {Lertxundi, U and Domingo-Echaburu, S and Ruiz-Osante, B and Hernandez Palacios, R and Peral Aguirregoitia, J and Medrano Albeniz, J}, title = {Comments on Duran et al.'s systematic review of anticholinergic risk scales (EJCP 2DOI 10.1007/s00228-013-1499-3).}, journal = {European journal of clinical pharmacology}, volume = {69}, number = {9}, pages = {1729}, pmid = {23740000}, issn = {1432-1041}, mesh = {Cholinergic Antagonists/*adverse effects ; Humans ; }, } @article {pmid23737298, year = {2013}, author = {Bonanno, GA}, title = {How prevalent is resilience following sexual assault?: comment on steenkamp et Al. (2012).}, journal = {Journal of traumatic stress}, volume = {26}, number = {3}, pages = {392-393}, doi = {10.1002/jts.21803}, pmid = {23737298}, issn = {1573-6598}, mesh = {Child Abuse, Sexual/*psychology ; Female ; Humans ; *Mental Recall ; *Repression, Psychology ; }, abstract = {Steenkamp, Dickstein, Salters-Pedneault, Hofmann, and Litz (2012) analyzed latent trajectories of posttraumatic stress disorder (PTSD) symptoms on data obtained in the early months following a single-incident sexual assault. In contrast to previous studies of potentially traumatic events, they did not observe a trajectory of minimal symptoms or resilience, which they argued occurred because sexual assault involves more severe and direct trauma exposure than examined in previous studies. Although sexual assault is an aversive and challenging event, it seems highly unlikely that at least some sexual assault survivors would not be resilient. Steenkamp et al.'s failure to observe resilience can easily be explained on purely methodological grounds. Most notably, their findings were probably heavily influenced by sampling bias. Additionally, their sample size was too small and had too much missing data for the kinds of latent trajectory modeling they attempted.}, } @article {pmid23711560, year = {2014}, author = {Cleaver, K}, title = {Attitudes of emergency care staff towards young people who self-harm: a scoping review.}, journal = {International emergency nursing}, volume = {22}, number = {1}, pages = {52-61}, doi = {10.1016/j.ienj.2013.04.001}, pmid = {23711560}, issn = {1878-013X}, mesh = {Adolescent ; *Attitude of Health Personnel ; *Emergency Nursing ; *Emergency Service, Hospital ; Humans ; Self-Injurious Behavior/*nursing ; }, abstract = {AIM: To determine whether reported attitudes towards patients who attend A&E following self-harm extend to young people.

BACKGROUND: Historically A&E staff have displayed negative attitudes towards patients who self-harm, although more recent research suggests that attitudes have shifted. There is retrospective evidence of low satisfaction with A&E services by individuals who self-harmed as adolescents, with comparatively little research which has specifically examined attitudes towards adolescent self-harm available.

METHOD: A scoping review of papers published from 2000 to 2012 was undertaken, papers accessed through the following databases, British Nursing Index, CINAHL, Medline, Psychology and Behavioural Science Collection, and PsychINFO. Hawker et al.'s (2002) methodology for critical appraisal was adopted.

RESULTS: Eleven papers derived from nine studies were located; three studies adopted qualitative methods, two mixed methods; the remainder were quantitative adopting a survey approach to measure attitudes. The studies revealed inconsistent findings, although the setting, patients' characteristics and education and training all appear to have a bearing on attitudes towards young people who self-harm.

CONCLUSION: Further research is required which considers attitudes of emergency care practitioners within the context of emergency care work, and which investigates whether being a young person per se has an influence on attitudes.}, } @article {pmid23708470, year = {2013}, author = {Bahari, SF and Clarke, S}, title = {Cross-validation of an employee safety climate model in Malaysia.}, journal = {Journal of safety research}, volume = {45}, number = {}, pages = {1-6}, doi = {10.1016/j.jsr.2012.12.003}, pmid = {23708470}, issn = {1879-1247}, mesh = {Adult ; Cross-Cultural Comparison ; Data Collection ; Factor Analysis, Statistical ; Female ; Humans ; *Industry ; Malaysia ; Male ; Middle Aged ; *Models, Theoretical ; *Organizational Culture ; *Safety Management ; Young Adult ; }, abstract = {PROBLEM: Whilst substantial research has investigated the nature of safety climate, and its importance as a leading indicator of organisational safety, much of this research has been conducted with Western industrial samples. The current study focuses on the cross-validation of a safety climate model in the non-Western industrial context of Malaysian manufacturing.

METHOD: The first-order factorial validity of Cheyne et al.'s (1998) [Cheyne, A., Cox, S., Oliver, A., Tomas, J.M., 1998. Modelling safety climate in the prediction of levels of safety activity. Work and Stress, 12(3), 255-271] model was tested, using confirmatory factor analysis, in a Malaysian sample.

RESULTS: Results showed that the model fit indices were below accepted levels, indicating that the original Cheyne et al. (1998) safety climate model was not supported. An alternative three-factor model was developed using exploratory factor analysis.

DISCUSSION: Although these findings are not consistent with previously reported cross-validation studies, we argue that previous studies have focused on validation across Western samples, and that the current study demonstrates the need to take account of cultural factors in the development of safety climate models intended for use in non-Western contexts.

IMPACT ON INDUSTRY: The results have important implications for the transferability of existing safety climate models across cultures (for example, in global organisations) and highlight the need for future research to examine cross-cultural issues in relation to safety climate.}, } @article {pmid23707358, year = {2013}, author = {Papachristou, H and Nederkoorn, C and Beunen, S and Jansen, A}, title = {Dissection of appetitive conditioning. Does impulsivity play a role?.}, journal = {Appetite}, volume = {69}, number = {}, pages = {46-53}, doi = {10.1016/j.appet.2013.05.011}, pmid = {23707358}, issn = {1095-8304}, mesh = {Adult ; *Appetite ; Cacao ; *Conditioning, Psychological ; Cues ; Extinction, Psychological ; Female ; Humans ; *Impulsive Behavior ; Learning ; Male ; }, abstract = {RATIONALE: It is generally assumed that cue-reactivity results from appetitive pavlovian learning. This is the reason for applying cue exposure with response prevention interventions in the treatment of substance and eating disorders. However, not all appetitive conditioned responses are equally sensitive to extinction. Additionally, impulsivity traits appear to moderate cue-reactivity. Nevertheless, there has been little research on the role of impulsivity traits in the learning of different appetitive response systems.

OBJECTIVES: The purpose of the present study was (i) to replicate Van Gucht et al.'s (2010) findings, in particular, the acquisition and the differential extinction of appetitive learned responses and ii) to investigate the role of impulsivity traits in appetitive learning.

METHODS: Participants (n=50) took part in a single laboratory session. Impulsivity traits (reward sensitivity, response inhibition, sensation seeking) were measured at the beginning of the session. A paradigm similar to Van Gucht et al.'s (2010) was used for the acquisition and extinction of subjective conditioned responses for milk chocolate (craving, expectancy, and liking).

RESULTS: The acquisition of appetitive responses was successful. Unlike craving and liking, the extinction of expectancy was fully successful. Impulsivity traits played no role in the acquisition and extinction of appetitive conditioning.

CONCLUSIONS: The results support the differential sensitivity of different appetitive response systems to extinction. The lack of findings for the role of impulsivity traits in appetitive learning shows that the question of how impulsivity affects appetitive behaviour still remains open. Theoretical and methodological issues and clinical implications of the findings are discussed.}, } @article {pmid23705936, year = {2013}, author = {Lorenc, T and Petticrew, M and Whitehead, M and Neary, D and Clayton, S and Wright, K and Thomson, H and Cummins, S and Sowden, A and Renton, A}, title = {Fear of crime and the environment: systematic review of UK qualitative evidence.}, journal = {BMC public health}, volume = {13}, number = {}, pages = {496}, pmid = {23705936}, issn = {1471-2458}, support = {09/3000/14/DH_/Department of Health/United Kingdom ; SRF-2010-03-05/DH_/Department of Health/United Kingdom ; }, mesh = {Crime/*psychology ; Databases, Factual ; Environment Design/*statistics & numerical data ; *Fear ; Humans ; Qualitative Research ; Risk Factors ; *Social Environment ; United Kingdom ; }, abstract = {BACKGROUND: The fear of crime may have negative consequences for health and wellbeing. It is influenced by factors in the physical and social environment. This study aimed to review and synthesize qualitative evidence from the UK on fear of crime and the environment.

METHODS: Eighteen databases were searched, including crime, health and social science databases. Qualitative studies conducted in the UK which presented data on fear of crime and the environment were included. Quality was assessed using Hawker et al.'s framework. Data were synthesized thematically.

RESULTS: A total of 40 studies were included in the review. Several factors in the physical environment are perceived to impact on fear of crime, including visibility and signs of neglect. However, factors in the local social environment appear to be more important as drivers of fear of crime, including social networks and familiarity. Broader social factors appear to be of limited relevance. There is considerable evidence for limitations on physical activity as a result of fear of crime, but less for mental health impacts.

CONCLUSIONS: Fear of crime represents a complex set of responses to the environment. It may play a role in mediating environmental impacts on health and wellbeing.}, } @article {pmid23692187, year = {2014}, author = {Desai, MJ and Shkolnikova, T and Nava, A and Inwald, D}, title = {A critical appraisal of the evidence for botulinum toxin type A in the treatment for cervico-thoracic myofascial pain syndrome.}, journal = {Pain practice : the official journal of World Institute of Pain}, volume = {14}, number = {2}, pages = {185-195}, doi = {10.1111/papr.12074}, pmid = {23692187}, issn = {1533-2500}, mesh = {Botulinum Toxins, Type A/adverse effects/*therapeutic use ; Cervical Vertebrae ; Evidence-Based Medicine ; Humans ; Myofascial Pain Syndromes/*drug therapy ; Neck Pain/drug therapy ; Neuromuscular Agents/adverse effects/*therapeutic use ; Randomized Controlled Trials as Topic ; Thoracic Vertebrae ; }, abstract = {Myofascial pain syndrome (MPS) is a musculoskeletal condition characterized by regional pain and muscle tenderness associated with the presence of myofascial trigger points (MTrPs). The last decade has seen an exponential increase in the use of botulinum toxin (BTX) to treat MPS. To understand the medical evidence substantiating the role of therapeutic BTX injections and to provide useful information for the medical practitioner, we applied the principles of evidence-based medicine to the treatment for cervico-thoracic MPS. A search was conducted through MEDLINE (PubMed, OVID, MDConsult), EMBASE, SCOPUS and the Cochrane database for the period 1966 to 2012 using the following keywords: myofascial pain, muscle pain, botulinum toxin, trigger points, and injections. A total of 7 trials satisfied our inclusion criteria and were evaluated in this review. Although the majority of studies found negative results, our analysis identified Gobel et al.'s as the highest quality study among these prospectively randomized investigations. This was due to appropriate identification of diagnostic criteria, excellent study design and objective endpoints. The 6 other identified studies had significant failings due to deficiencies in 1 or more major criteria. We conclude that higher quality, rigorously standardized studies are needed to more appropriately investigate this promising treatment modality.}, } @article {pmid23689993, year = {2013}, author = {Kumari, S and Khan, MK and Kumar, R}, title = {Cryptanalysis and improvement of 'A privacy enhanced scheme for telecare medical information systems'.}, journal = {Journal of medical systems}, volume = {37}, number = {4}, pages = {9952}, pmid = {23689993}, issn = {1573-689X}, mesh = {*Computer Security ; *Confidentiality ; Humans ; Information Systems/*organization & administration ; Telemedicine/*organization & administration ; }, abstract = {To ensure reliable telecare services some user authentication schemes for telecare medical information system (TMIS) have been presented in literature. These schemes are proposed with intent to regulate only authorized access to medical services so that medical information can be protected from misuse. Very recently Jiang et al. proposed a user authentication scheme for TMIS which they claimed to provide enhanced privacy. They made use of symmetric encryption/decryption with cipher block chaining mode (CBC) to achieve the claimed user privacy. Their scheme provides features like user anonymity and user un-traceability unlike its preceding schemes on which it is built. Unluckily, authors overlook some important aspects in designing their scheme due to which it falls short to resist user impersonation attack, guessing attacks and denial of service attack. Besides, its password change phase is not secure; air message confidentiality is at risk and also has some other drawbacks. Therefore, we propose an improved scheme free from problems observed in Jiang et al.'s scheme and more suitable for TMIS.}, } @article {pmid23689688, year = {2013}, author = {Olesen, TH and Torfing, T and Overgaard, S}, title = {MPR realignment increases accuracy when measuring femoral neck anteversion angle.}, journal = {Skeletal radiology}, volume = {42}, number = {8}, pages = {1119-1125}, pmid = {23689688}, issn = {1432-2161}, mesh = {Adolescent ; Adult ; *Algorithms ; Child ; Female ; Femur Neck/*abnormalities/*diagnostic imaging ; Hip Dislocation/*diagnostic imaging ; Humans ; Male ; Middle Aged ; Patient Positioning/*methods ; Radiographic Image Enhancement/*methods ; Reproducibility of Results ; Sensitivity and Specificity ; Tomography, X-Ray Computed/*methods ; Young Adult ; }, abstract = {OBJECTIVE: To compare two methods of measuring femoral neck anteversion angle (FNA): A 2D method used at Odense University Hospital until 2010, and a method labeled 3D-OUH. The latter method makes corrections to compensate for errors introduced by the individual placement of patients in the CT scanner.

MATERIALS AND METHODS: Twenty-six CT-examined patients were included: nine men and 17 women. The right side FNA was measured twice with each method by one observer, measuring intraobserver variability. Both methods are based on the following anatomy: femoral head center, center at the level of lesser trochanter and posterior apex of the femoral condyles. The 3D-OUH method corrects for the individual orientation of femur by realigning it prior to measurement, in accordance to Murphy et al.'s original definition of FNA. The intercondylar notch center of the knee and center at lesser trochanter was used in the realignment.

RESULTS: The 2D method significantly overestimated FNA compared to 3D-OUH by 4.2° (95 % CI: 2.8°; 5.6°), p < 0.0001. All measurements with the 3D method needed clock-wise correction in the coronal plane, suggesting patient positioning as a consistent source of overestimation by the 2D method. The 3D-OUH method had a lower intraobserver variability with a limit of agreement (LOA) of -2.4° to 2.1° against that of the 2D method of -3.4° to 3.8°

CONCLUSIONS: Mean anteversion was 4.2° (95 % CI: 2.8°; 5.6°) lower with the 3D-OUH method than with the 2D method. The 3D-OUH method eliminated an obvious source of error, namely the individual orientation of femur during CT-examination. Moreover, intraobserver variability was improved with the 3D-OUH method.}, } @article {pmid23683176, year = {2013}, author = {Akintola, O and Hlengwa, WM and Dageid, W}, title = {Perceived stress and burnout among volunteer caregivers working in AIDS care in South Africa.}, journal = {Journal of advanced nursing}, volume = {69}, number = {12}, pages = {2738-2749}, doi = {10.1111/jan.12166}, pmid = {23683176}, issn = {1365-2648}, mesh = {Acquired Immunodeficiency Syndrome/*nursing ; *Burnout, Professional ; Caregivers/*psychology ; Cross-Sectional Studies ; Humans ; South Africa ; *Stress, Psychological ; Volunteers/*psychology ; }, abstract = {AIMS: To conduct a quantitative investigation of stress and the relationship with burnout among AIDS care volunteers.

BACKGROUND: Volunteer caregivers experience stress that could lead to burnout. Yet, very few studies quantify stress and its relationship with burnout among AIDS care volunteers.

DESIGN: This study uses a cross-sectional, exploratory survey design.

METHODS: Face-to-face interviews were conducted with 126 volunteer caregivers working in 13 semi-rural communities (townships) in Durban, South Africa in April 2009. All participants were women, Christian and with low levels of education. A 22-item instrument was drawn from Pearlin et al.'s role overload and role captivity scales, Van Dyk's stress factor scale and the Maslach Burnout Inventory.

RESULTS: Most of the volunteers had moderate-to-high levels of stress. 'Role/work overload' 'lack of support' and 'overwhelming nature of the disease' explained most of the variance in stress. Volunteers' age and number of patients in their care were predictors of stress. Caring for only AIDS patients, lack of support, stress emanating from perceived stigma and lack of training; and the overwhelming nature of AIDS were predictors of burnout.

CONCLUSION: High levels of stress could negatively impact volunteers' health and well-being and on-the-job performance. Policy makers must develop and fund home-based care models that take into account the stressors associated with AIDS care, by reducing the work load, providing ongoing psychosocial support and recruiting nurses to assist volunteers. The small non-probability sample used in this study highlights the need to treat the findings with caution.}, } @article {pmid23674466, year = {2013}, author = {Melo, SS and Bentall, RP}, title = {'Poor me' versus 'Bad me' paranoia: the association between self-beliefs and the instability of persecutory ideation.}, journal = {Psychology and psychotherapy}, volume = {86}, number = {2}, pages = {146-163}, doi = {10.1111/j.2044-8341.2011.02051.x}, pmid = {23674466}, issn = {2044-8341}, mesh = {*Adaptation, Psychological ; Adolescent ; Adult ; Aged ; Cross-Sectional Studies ; Delusions/*psychology ; England ; Female ; Humans ; Internal-External Control ; Interview, Psychological ; Longitudinal Studies ; Male ; Middle Aged ; Models, Psychological ; Paranoid Disorders/*psychology ; Psychiatric Status Rating Scales/statistics & numerical data ; *Self Concept ; Severity of Illness Index ; Social Support ; Statistics as Topic ; Young Adult ; }, abstract = {OBJECTIVES: To investigate whether different self-attributes would be associated with different degrees of deservedness of persecution in a clinical paranoid sample.

BACKGROUND: Some studies have shown differences between the self-esteem (SE) of individuals with 'Poor Me' (PM) and 'Bad Me' (BM) paranoia (Bentall et al., 2009; Chadwick, Trower, Juusti-Butler, & Maguire, 2005). Most studies investigating this relationship have employed a cross-sectional design, precluding the investigation of changes over time.

METHODS: In the cross-sectional part of the study, 45 clinical participants and 25 controls were assessed in terms of paranoia, deservedness of persecution, SE, self-discrepancies, daily events, and coping strategies. In the longitudinal part of the study, the clinical group was re-assessed over a period of another 2 days, in order to study changes in these variables.

RESULTS: At baseline, there were no differences between the SE of the two paranoia presentations, which was significantly lower than the controls'. However, the paired-samples repeated analysis found the SE of individuals when in a PM presentation was higher than when they were BM. Only BM paranoia was found to be associated with higher self-ideal:self-actual self-discrepancies than the other groups. The longitudinal analysis indicated that, having been PM and having low SE at the previous assessment day made it more likely that individuals would be in BM subsequently. No differences in causal attributions made for ecological events were found between the groups. Higher SE was found to be more likely when individuals coped with adversities by using social support.

CONCLUSIONS: Both deservedness of persecution and self-views appear to be unstable in individuals with paranoia and to change consistently over time, a finding which is in keeping with Bentall et al.'s (2001) dynamic model of paranoia.}, } @article {pmid23671920, year = {2013}, author = {Bierne, N and Roze, D and Welch, JJ}, title = {Pervasive selection or is it…? Why are FST outliers sometimes so frequent?.}, journal = {Molecular ecology}, volume = {22}, number = {8}, pages = {2061-2064}, doi = {10.1111/mec.12241}, pmid = {23671920}, issn = {1365-294X}, mesh = {Adaptation, Biological/*genetics ; *Ecotype ; *Models, Theoretical ; *Selection, Genetic ; }, abstract = {It is now common for population geneticists to estimate FST for a large number of loci across the genome, before testing for selected loci as being outliers to the FST distribution. One surprising result of such FST scans is the often high proportion (>1% and sometimes >10%) of outliers detected, and this is often interpreted as evidence for pervasive local adaptation. In this issue of Molecular Ecolog, Fourcade et al. (2013) observe that a particularly high rate of FST outliers has often been found in river organisms, such as fishes or damselflies, despite there being no obvious reason why selection should affect a larger proportion of the genomes of these organisms. Using computer simulations, Fourcade et al. (2013) show that the strong correlation in co-ancestry produced in long onedimensional landscapes (such as rivers, valleys, peninsulas, oceanic ridges or coastlines) greatly increases the neutral variance in FST, especially when the landscape is further reticulated into fractal networks. As a consequence, outlier tests have a high rate of false positives, unless this correlation can be taken into account. Fourcade et al.'s study highlights an extreme case of the general problem, first noticed by Robertson (1975a,b) and Nei & Maruyama (1975), that correlated co-ancestry inflates the neutral variance in FST when compared to its expectation under an island model of population structure. Similar warnings about the validity of outlier tests have appeared regularly since then but have not been widely cited in the recent genomics literature. We further emphasize that FST outliers can arise in many different ways and that outlier tests are not designed for situations where the genetic architecture of local adaptation involves many loci.}, } @article {pmid23669175, year = {2013}, author = {Smith, JL and Barry, RJ and Steiner, GZ}, title = {CNV resolution does not cause NoGo anteriorisation of the P3: a failure to replicate Simson et al.}, journal = {International journal of psychophysiology : official journal of the International Organization of Psychophysiology}, volume = {89}, number = {3}, pages = {349-357}, doi = {10.1016/j.ijpsycho.2013.05.002}, pmid = {23669175}, issn = {1872-7697}, mesh = {Acoustic Stimulation ; Adult ; *Brain Mapping ; Contingent Negative Variation/*physiology ; Cues ; Decision Making ; Electroencephalography ; Event-Related Potentials, P300/*physiology ; Female ; Humans ; *Inhibition, Psychological ; Male ; Neuropsychological Tests ; Photic Stimulation ; Principal Component Analysis ; Psychomotor Performance/physiology ; Reaction Time/physiology ; Time Factors ; Young Adult ; }, abstract = {For 35 years, some researchers have argued that CNV resolution may affect or even produce the increased P3 for NoGo compared to Go trials, and thus that no 'inhibitory' NoGo P3 exists. This is based on the work of Simson et al. (1977b), the scalp topography of potentials in auditory and visual Go/NoGo tasks. Electroencephalography and Clinical Neurophysiology, 43, 864-875, which compared Go and NoGo topography after CNV was subtracted from NoGo trials only. Specifically, the NoGo P3 topography showed the distinctive frontocentral maximum, which is often linked to motor inhibition, when referenced to a pre-target baseline. This NoGo topography changed to a more parietal maximum, similar to that on Go trials, when referenced to a pre-cue baseline. Many researchers have cited this study, while failing to use the delayed response design on which Simson et al. based their argument. We attempted to replicate Simson et al.'s experiment with delayed responses and also with immediate responses, as are more often used. As expected, the amplitudes of CNV and P3 to both Go and NoGo trials were increased when immediate compared to delayed responses were required, but we failed to replicate the topographic shift of NoGo P3 with different baselines for both delayed and immediate responses. That is, subtraction of the CNV from NoGo P3 did not change the distinctive frontocentral topography of this component. The results suggest that CNV may affect the amplitude and measurement of the NoGo P3, but that NoGo P3 anteriorisation is not caused by CNV resolution.}, } @article {pmid23660745, year = {2013}, author = {Das, AK and Goswami, A}, title = {A secure and efficient uniqueness-and-anonymity-preserving remote user authentication scheme for connected health care.}, journal = {Journal of medical systems}, volume = {37}, number = {3}, pages = {9948}, pmid = {23660745}, issn = {1573-689X}, mesh = {Algorithms ; *Computer Security ; *Confidentiality ; Health Smart Cards ; Humans ; Information Systems ; Telemedicine ; }, abstract = {Connected health care has several applications including telecare medicine information system, personally controlled health records system, and patient monitoring. In such applications, user authentication can ensure the legality of patients. In user authentication for such applications, only the legal user/patient himself/herself is allowed to access the remote server, and no one can trace him/her according to transmitted data. Chang et al. proposed a uniqueness-and-anonymity-preserving remote user authentication scheme for connected health care (Chang et al., J Med Syst 37:9902, 2013). Their scheme uses the user's personal biometrics along with his/her password with the help of the smart card. The user's biometrics is verified using BioHashing. Their scheme is efficient due to usage of one-way hash function and exclusive-or (XOR) operations. In this paper, we show that though their scheme is very efficient, their scheme has several security weaknesses such as (1) it has design flaws in login and authentication phases, (2) it has design flaws in password change phase, (3) it fails to protect privileged insider attack, (4) it fails to protect the man-in-the middle attack, and (5) it fails to provide proper authentication. In order to remedy these security weaknesses in Chang et al.'s scheme, we propose an improvement of their scheme while retaining the original merit of their scheme. We show that our scheme is efficient as compared to Chang et al.'s scheme. Through the security analysis, we show that our scheme is secure against possible attacks. Further, we simulate our scheme for the formal security verification using the widely-accepted AVISPA (Automated Validation of Internet Security Protocols and Applications) tool to ensure that our scheme is secure against passive and active attacks. In addition, after successful authentication between the user and the server, they establish a secret session key shared between them for future secure communication.}, } @article {pmid23659847, year = {2013}, author = {McAuliffe, WE}, title = {A critique of Minozzi et al.'s pain relief and dependence systematic review.}, journal = {Addiction (Abingdon, England)}, volume = {108}, number = {6}, pages = {1162-1169}, doi = {10.1111/add.12181}, pmid = {23659847}, issn = {1360-0443}, mesh = {Acute Pain/*prevention & control ; Analgesics, Opioid/*adverse effects ; Chronic Pain/*prevention & control ; Humans ; Opioid-Related Disorders/*etiology ; Prescription Drug Misuse/*adverse effects ; }, } @article {pmid23643183, year = {2013}, author = {Seo, YP and Seo, Y}, title = {Analysis of giant electrorheological fluids.}, journal = {Journal of colloid and interface science}, volume = {402}, number = {}, pages = {90-93}, doi = {10.1016/j.jcis.2013.03.046}, pmid = {23643183}, issn = {1095-7103}, abstract = {The yield stress dependence on electric field strength for giant electrorheological (GER) fluids over the full range of electric fields was examined using Seo's scaling function which incorporated both the polarization and the conductivity models. If a proper scaling was applied to the yield stress data to collapse them onto a single curve, the Seo's scaling function could correctly fit the yield stress behavior of GER suspensions, even at very high electric field strengths. The model predictions were also compared with recently proposed Choi et al.'s model to allow a consideration of the universal framework of ER fluids.}, } @article {pmid23628345, year = {2013}, author = {Morris, RG}, title = {NMDA receptors and memory encoding.}, journal = {Neuropharmacology}, volume = {74}, number = {}, pages = {32-40}, doi = {10.1016/j.neuropharm.2013.04.014}, pmid = {23628345}, issn = {1873-7064}, support = {G0700447/MRC_/Medical Research Council/United Kingdom ; G9200370/MRC_/Medical Research Council/United Kingdom ; }, mesh = {2-Amino-5-phosphonovalerate/pharmacology ; Animals ; Hippocampus/drug effects/physiology ; Learning/drug effects/physiology ; Long-Term Potentiation/drug effects/genetics/physiology ; Memory/drug effects/*physiology ; Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors/genetics/*physiology ; }, abstract = {It is humbling to think that 30 years have passed since the paper by Collingridge, Kehl and McLennan showing that one of Jeff Watkins most interesting compounds, R-2-amino-5-phosphonopentanoate (d-AP5), blocked the induction of long-term potentiation in vitro at synapses from area CA3 of the hippocampus to CA1 without apparent effect on baseline synaptic transmission (Collingridge et al., 1983). This dissociation was one of the key triggers for an explosion of interest in glutamate receptors, and much has been discovered since that collectively contributes to our contemporary understanding of glutamatergic synapses - their biophysics and subunit composition, of the agonists and antagonists acting on them, and their diverse functions in different networks of the brain and spinal cord. It can be fairly said that Collingridge et al.'s (1983) observation was the stimulus that has led, on the one hand, to structural biological work at the atomic scale describing the key features of NMDA receptors that enables their coincidence function to happen; and, on the other, to work with whole animals investigating the contributions that calcium signalling via this receptor can have on rhythmical activities controlled by spinal circuits, memory encoding in the hippocampus (the topic of this article), visual cortical plasticity, sensitization in pain, and other functions. In this article, I lay out how my then interest in long-term potentiation (LTP) as a model of memory enabled me to recognise the importance of Collingridge et al.'s discovery - and how I and my colleagues endeavoured to take things forward in the area of learning and memory. This is in some respects a personal story, and I tell it as such. The idea that NMDA receptor activation is essential for memory encoding, though not for storage, took time to develop and to be accepted. Along the way, there have been confusions, challenges, and surprises surrounding the idea that activation of NMDA receptors can trigger memory. Some of these are described and how they have been addressed and resolved. Last, I touch on some new directions of interest with respect to the functional role of the NMDA receptor in cognition. This article is part of the Special Issue entitled 'Glutamate Receptor-Dependent Synaptic Plasticity'.}, } @article {pmid23628290, year = {2013}, author = {Magnuski, M and Gola, M}, title = {It's not only in the eyes: nonlinear relationship between face orientation and N170 amplitude irrespective of eye presence.}, journal = {International journal of psychophysiology : official journal of the International Organization of Psychophysiology}, volume = {89}, number = {3}, pages = {358-365}, doi = {10.1016/j.ijpsycho.2013.04.016}, pmid = {23628290}, issn = {1872-7697}, mesh = {Adolescent ; Adult ; Analysis of Variance ; Electroencephalography ; Evoked Potentials/*physiology ; *Eye ; *Face ; Female ; Humans ; Male ; *Nonlinear Dynamics ; Orientation/*physiology ; Pattern Recognition, Visual/*physiology ; Photic Stimulation ; Reaction Time/physiology ; Recognition, Psychology ; Young Adult ; }, abstract = {We have investigated the interplay between face orientation, eye presence, and N170 amplitude by recording Event Related Potentials. To clarify previous reports of nonlinearity in N170 amplitude changes along rotation angle changes, we adopted Itier et al.'s model (Itier et al., 2007) which links N170 face inversion effects with the presence of eyes. Comparison of N170 amplitude and latency for five stimulus categories (Faces-with-eyes, Faces-without-eyes, Eyes, Cars-with-lights, Cars-without-lights) in five different rotations (0, 45, 90, 135, 180) resulted in mixed conclusions. The main findings of this study are as follows: (1) a strong nonlinear relationship between N170 and angle of rotation that is specific to faces, distinguishing face from car category even when no significant differences were observed between these categories for upright and inverted orientations; and (2) the nonlinear relationship between N170 and angle of rotation does not depend on eye presence. We also propose an alternative model according to which N170 amplitude consists of two related aspects of face processing: (A) incompatibility (relative distance of the stimulus pattern from experience-based hypothetical prototype) and (B) integration (degree to which stimulus is integrated into holistic representation), with the former affecting the latter. Moreover, we suggest two possible neural events underlying these two aspects of face processing: neural population size activated by the stimulus, and synchronization within this population.}, } @article {pmid23626531, year = {2013}, author = {Schultheiss, OC and Schiepe-Tiska, A}, title = {The role of the dorsoanterior striatum in implicit motivation: the case of the need for power.}, journal = {Frontiers in human neuroscience}, volume = {7}, number = {}, pages = {141}, pmid = {23626531}, issn = {1662-5161}, abstract = {Implicit motives like the need for power (nPower) scale affective responses to need-specific rewards or punishments and thereby influence activity in motivational-brain structures. In this paper, we review evidence specifically supporting a role of the striatum in nPower. Individual differences in nPower predict (1) enhanced implicit learning accuracy, but not speed, on serial-response tasks that are reinforced by power-related incentives (e.g., winning or losing a contest; dominant or submissive emotional expressions) in behavioral studies and (2) activation of the anterior caudate in response to dominant emotional expressions in brain imaging research. We interpret these findings on the basis of Hikosaka et al.'s (2002a) model of central mechanisms of motor skill learning. The model assigns a critical role to the dorsoanterior striatum in dopamine-driven learning of spatial stimulus sequences. Based on this model, we suggest that the dorsoanterior striatum is the locus of nPower-dependent reinforcement. However, given the centrality of this structure in a wide range of motivational pursuits, we also propose that activity in the dorsoanterior striatum may not only reflect individual differences in nPower, but also in other implicit motives, like the need for achievement or the need for affiliation, provided that the proper incentives for these motives are present during reinforcement learning. We discuss evidence in support of such a general role of the dorsoanterior striatum in implicit motivation.}, } @article {pmid23608175, year = {2013}, author = {Miquel, J and Świderski, Z}, title = {Spermatological characteristics of the Trypanorhyncha inferred from new ultrastructural data on species of Tentaculariidae, Eutetrarhynchidae, and Progrillotiidae.}, journal = {Comptes rendus biologies}, volume = {336}, number = {2}, pages = {65-72}, doi = {10.1016/j.crvi.2013.02.005}, pmid = {23608175}, issn = {1768-3238}, mesh = {Animals ; Cell Nucleus/ultrastructure ; Fishes/*physiology ; Male ; Microscopy, Electron ; Microtubules/ultrastructure ; Species Specificity ; Spermatogenesis ; Spermatozoa/physiology/*ultrastructure ; }, abstract = {The present study focuses on the ultrastructural characteristics of both spermiogenesis and the spermatozoon in the order Trypanorhyncha. New ultrastructural data are presented for two species of the unexplored superfamily Tentacularioidea, Nybelinia queenslandensis, and Kotorella pronosoma. The present study also provides supplementary data on the superfamily Eutetrarhynchoidea, with the analysis of spermiogenesis and spermatozoon of two progrillotiids, Progrillotia dasyatidis and Pro. pastinacae, and new ultrastructural data concerning spermiogenesis in the eutetrarhynchids Dollfusiella spinulifera and Parachristianella trygonis. Spermiogenesis in trypanorhynchs follows the Bâ and Marchand's type I and the ultrastructural organisation of the mature spermatozoon corresponds to the Levron et al.'s type I. The most remarkable characters concerns the number of electron-dense plates constituting the intercentriolar body during spermiogenesis and in the variability of the arc-like row of thick cortical microtubules present in the anterior areas of the spermatozoon because of its variability according to the species.}, } @article {pmid23606136, year = {2013}, author = {Maquestiaux, F and Didierjean, A and Ruthruff, E and Chauvel, G and Hartley, A}, title = {Lost ability to automatize task performance in old age.}, journal = {Psychonomic bulletin & review}, volume = {20}, number = {6}, pages = {1206-1212}, pmid = {23606136}, issn = {1531-5320}, mesh = {Aged ; Aging/*psychology ; Attention/*physiology ; Female ; Humans ; Male ; Middle Aged ; *Practice, Psychological ; Psychomotor Performance/*physiology ; Reaction Time/physiology ; Refractory Period, Psychological/*physiology ; }, abstract = {Can elderly adults automatize a new task? To address this question, 10 older adults each performed 10,080 training trials over 12 sessions on an easy but novel task. The psychological refractory period (PRP) procedure was then used to evaluate whether this highly practiced task, when presented as task 2 along with an unpracticed task 1, could proceed automatically. If automatic, task 2 processing should bypass the bottleneck and, therefore, not be delayed while central attention is devoted to task 1, yielding little dual-task interference. This is exactly what Maquestiaux, Laguë-Beauvais, Ruthruff, and Bherer (Memory and Cognition 36:1262-1282, 2008) previously observed for almost all younger adults, even with half the training on a more difficult task. Although extensive training reduced older adults' reaction times to only 307 ms, a value virtually identical to that attained by Maquestiaux et al.'s (Memory and Cognition 36:1262-1282, 2008) younger adults, the highly practiced task 2 was slowed by 485 ms in the dual-task PRP procedure. Such a large slowing in older adults is striking given the easy tasks and massive amounts of practice. These findings demonstrate a qualitative change with age, in which older adults lose the ability to automatize novel tasks, which cannot be attributed merely to generalized cognitive slowing.}, } @article {pmid23571071, year = {2013}, author = {Thompson, VA and Ackerman, R and Sidi, Y and Ball, LJ and Pennycook, G and Prowse Turner, JA}, title = {The role of answer fluency and perceptual fluency in the monitoring and control of reasoning: reply to Oppenheimer, and Epley (2013).}, journal = {Cognition}, volume = {128}, number = {2}, pages = {256-258}, doi = {10.1016/j.cognition.2013.03.003}, pmid = {23571071}, issn = {1873-7838}, mesh = {Cognition/*physiology ; Female ; Humans ; Male ; Psychomotor Performance/*physiology ; Thinking/*physiology ; }, abstract = {In this reply, we provide an analysis of Alter et al. (2013) response to our earlier paper (Thompson et al., 2013). In that paper, we reported difficulty in replicating Alter, Oppenheimer, Epley, and Eyre's (2007) main finding, namely that a sense of disfluency produced by making stimuli difficult to perceive, increased accuracy on a variety of reasoning tasks. Alter, Oppenheimer, and Epley (2013) argue that we misunderstood the meaning of accuracy on these tasks, a claim that we reject. We argue and provide evidence that the tasks were not too difficult for our populations (such that no amount of "metacognitive unease" would promote correct responding) and point out that in many cases performance on our tasks was well above chance or on a par with Alter et al.'s (2007) participants. Finally, we reiterate our claim that the distinction between answer fluency (the ease with which an answer comes to mind) and perceptual fluency (the ease with which a problem can be read) is genuine, and argue that Thompson et al. (2013) provided evidence that these are distinct factors that have different downstream effects on cognitive processes.}, } @article {pmid23550969, year = {2013}, author = {Lee, K and Bull, R and Ho, RM}, title = {Developmental changes in executive functioning.}, journal = {Child development}, volume = {84}, number = {6}, pages = {1933-1953}, doi = {10.1111/cdev.12096}, pmid = {23550969}, issn = {1467-8624}, mesh = {Adolescent ; Adolescent Development/*physiology ; Aging/physiology ; Child ; Child Development/*physiology ; Child, Preschool ; Cohort Studies ; Executive Function/*physiology ; Female ; Humans ; Inhibition, Psychological ; Male ; Memory, Short-Term/physiology ; Pattern Recognition, Visual/physiology ; Psychomotor Performance/physiology ; Reaction Time ; }, abstract = {Although early studies of executive functioning in children supported Miyake et al.'s (2000) three-factor model, more recent findings supported a variety of undifferentiated or two-factor structures. Using a cohort-sequential design, this study examined whether there were age-related differences in the structure of executive functioning among 6- to 15-year-olds (N = 688). Children were tested annually on tasks designed to measure updating and working memory, inhibition, and switch efficiency. There was substantial task-based variation in developmental patterns on the various tasks. Confirmatory factor analyses and tests for longitudinal factorial invariance showed that data from the 5- to 13-year-olds conformed to a two-factor structure. For the 15-year-olds, a well-separated three-factor structure was found.}, } @article {pmid23526346, year = {2012}, author = {Relethford, JH}, title = {Commentary on Sokal et al.'s "historical population movements in Europe influence genetic relationships in modern samples" (1996).}, journal = {Human biology}, volume = {84}, number = {5}, pages = {607-608}, doi = {10.3378/027.084.0510}, pmid = {23526346}, issn = {1534-6617}, mesh = {*Gene Frequency ; *Genetics, Population ; Humans ; *Population Dynamics ; White People/*genetics ; }, } @article {pmid23526344, year = {2012}, author = {Heggarty, P}, title = {Commentary on Chen et al.'s "worldwide analysis of genetic and linguistic relationships of human populations" (1995).}, journal = {Human biology}, volume = {84}, number = {5}, pages = {573-580}, doi = {10.3378/027.084.0508}, pmid = {23526344}, issn = {1534-6617}, mesh = {*Genetics, Population ; Humans ; *Linguistics ; *Population Dynamics ; }, } @article {pmid23519852, year = {2013}, author = {Ghritlaharey, RK and Budhwani, KS}, title = {Two-staged management for all types of congenital pouch colon.}, journal = {African journal of paediatric surgery : AJPS}, volume = {10}, number = {1}, pages = {17-23}, doi = {10.4103/0189-6725.109378}, pmid = {23519852}, issn = {0974-5998}, mesh = {Colon/*abnormalities/diagnostic imaging/surgery ; Colonic Diseases/congenital/physiopathology/*surgery ; Colostomy/*methods ; Defecation ; Female ; Follow-Up Studies ; Humans ; Infant, Newborn ; Ligation ; Male ; Radiography, Abdominal ; Retrospective Studies ; Treatment Outcome ; }, abstract = {BACKGROUND: The aim of this study was to review our experience with two-staged management for all types of congenital pouch colon (CPC).

PATIENTS AND METHODS: This retrospective study included CPC cases that were managed with two-staged procedures in the Department of Paediatric Surgery, over a period of 12 years from 1 January 2000 to 31 December 2011.

RESULTS: CPC comprised of 13.71% (97 of 707) of all anorectal malformations (ARM) and 28.19% (97 of 344) of high ARM. Eleven CPC cases (all males) were managed with two-staged procedures. Distribution of cases (Narsimha Rao et al.'s classification) into types I, II, III, and IV were 1, 2, 6, and 2, respectively. Initial operative procedures performed were window colostomy (n = 6), colostomy proximal to pouch (n = 4), and ligation of colovesical fistula and end colostomy (n = 1). As definitive procedures, pouch excision with abdomino-perineal pull through (APPT) of colon in eight, and pouch excision with APPT of ileum in three were performed. The mean age at the time of definitive procedures was 15.6 months (ranges from 3 to 53 months) and the mean weight was 7.5 kg (ranges from 4 to 11 kg). Good fecal continence was observed in six and fair in two cases in follow-up periods, while three of our cases lost to follow up. There was no mortality following definitive procedures amongst above 11 cases.

CONCLUSIONS: Two-staged procedures for all types of CPC can also be performed safely with good results. The most important fact that the definitive procedure is being done without protective stoma and therefore, it avoids stoma closure, stoma-related complications, related cost of stoma closure and hospital stay.}, } @article {pmid23519594, year = {2013}, author = {Rind, B}, title = {Homosexual orientation-from nature, not abuse: A critique of Roberts, Glymour, and Koenen (2013).}, journal = {Archives of sexual behavior}, volume = {42}, number = {8}, pages = {1653-1664}, doi = {10.1007/s10508-013-0080-6}, pmid = {23519594}, issn = {1573-2800}, mesh = {Adult Survivors of Child Abuse/*psychology ; Child Abuse/*psychology ; Female ; Humans ; Male ; Sexual Behavior/*psychology ; }, abstract = {Roberts, Glymour, and Koenen (2013), using instrumental variable models, argued that child abuse causes homosexual orientation, defined in part as any same-sex attractions. Their instruments were various negative family environment factors. In their analyses, they found that child sexual abuse (CSA) was more strongly related to homosexual orientation than non-sexual maltreatment was, especially among males. The present commentary therefore focused on male CSA. It is argued that Roberts et al.'s "abuse model" is incorrect and an alternative is presented. Male homosexual behavior is common in primates and has been common in many human societies, such that an evolved human male homosexual potential, with individual variation, can be assumed. Cultural variation has been strongly influenced by cultural norms. In our society, homosexual expression is rare because it is counternormative. The "counternormativity model" offered here holds that negative family environment weakens normative controls and increases counternormative thinking and behavior, which, in combination with sufficient homosexual potential and relevant, reinforcing experiences, can produce a homosexual orientation. This is a benign or positive model (innate potential plus release and reinforcement), in contrast to Roberts et al.'s negative model (abuse plus emotional compensation or cognitive distortion). The abuse model is criticized for being based on the sexual victimological paradigm, which developed to describe the female experience in rape and incest. This poorly fits the gay male experience, as demonstrated in a brief non-clinical literature review. Validly understanding male homosexuality, it is argued, requires the broad perspective, as employed here.}, } @article {pmid23494087, year = {2013}, author = {Farwell, LA and Richardson, DC}, title = {Brain fingerprinting: let's focus on the science-a reply to Meijer, Ben-Shakhar, Verschuere, and Donchin.}, journal = {Cognitive neurodynamics}, volume = {7}, number = {2}, pages = {159-166}, pmid = {23494087}, issn = {1871-4080}, abstract = {Farwell in Cogn Neurodyn 6:115-154, (2012) reviewed all research on brainwave-based detection of concealed information published in English, including the author's laboratory and field research. He hypothesized that specific methods are sufficient to obtain less than 1 % error rate and high statistical confidence, and some of them are necessary. Farwell proposed 20 brain fingerprinting scientific standards embodying these methods. He documented the fact that all previous research and data are compatible with these hypotheses and standards. Farwell explained why failure to meet these standards resulted in decrements in performance of other, alternative methods. Meijer et al. criticized Farwell in Cogn Neurodyn 6:115-154, (2012) and Farwell personally. The authors stated their disagreement with Farwell's hypotheses, but did not cite any data that contradict the three hypotheses, nor did they propose alternative hypotheses or standards. Meijer et al. made demonstrable misstatements of fact, including false ad hominem statements about Farwell, and impugned Farwell's motives and character. We provide supporting evidence for Farwell's three hypotheses, clarify several issues, correct Meijer et al.'s misstatements of fact, and propose that the progress of science is best served by practicing science: designing and conducting research to test and as necessary modify the proposed hypotheses and standards that explain the existing data.}, } @article {pmid23488833, year = {2013}, author = {Carle, C and Alexander, P and Columb, M and Johal, J}, title = {Design and internal validation of an obstetric early warning score: secondary analysis of the Intensive Care National Audit and Research Centre Case Mix Programme database.}, journal = {Anaesthesia}, volume = {68}, number = {4}, pages = {354-367}, doi = {10.1111/anae.12180}, pmid = {23488833}, issn = {1365-2044}, mesh = {Adolescent ; Adult ; Area Under Curve ; Critical Care/*methods/standards/statistics & numerical data ; Databases, Factual/*statistics & numerical data ; Diagnosis-Related Groups/*statistics & numerical data ; Female ; Hospital Information Systems/standards/statistics & numerical data ; Hospital Mortality ; Humans ; Intensive Care Units/statistics & numerical data ; Medical Audit/methods/*statistics & numerical data ; Middle Aged ; Obstetrics/methods/statistics & numerical data ; Obstetrics and Gynecology Department, Hospital/standards/statistics & numerical data ; Pregnancy ; Pregnancy Complications/*diagnosis/epidemiology/therapy ; ROC Curve ; Reproducibility of Results ; Retrospective Studies ; Severity of Illness Index ; Survival Analysis ; United Kingdom/epidemiology ; *Vital Signs ; Young Adult ; }, abstract = {We designed and internally validated an aggregate weighted early warning scoring system specific to the obstetric population that has the potential for use in the ward environment. Direct obstetric admissions from the Intensive Care National Audit and Research Centre's Case Mix Programme Database were randomly allocated to model development (n = 2240) or validation (n = 2200) sets. Physiological variables collected during the first 24 h of critical care admission were analysed. Logistic regression analysis for mortality in the model development set was initially used to create a statistically based early warning score. The statistical score was then modified to create a clinically acceptable early warning score. Important features of this clinical obstetric early warning score are that the variables are weighted according to their statistical importance, a surrogate for the FI O2 /Pa O2 relationship is included, conscious level is assessed using a simplified alert/not alert variable, and the score, trigger thresholds and response are consistent with the new non-obstetric National Early Warning Score system. The statistical and clinical early warning scores were internally validated using the validation set. The area under the receiver operating characteristic curve was 0.995 (95% CI 0.992-0.998) for the statistical score and 0.957 (95% CI 0.923-0.991) for the clinical score. Pre-existing empirically designed early warning scores were also validated in the same way for comparison. The area under the receiver operating characteristic curve was 0.955 (95% CI 0.922-0.988) for Swanton et al.'s Modified Early Obstetric Warning System, 0.937 (95% CI 0.884-0.991) for the obstetric early warning score suggested in the 2003-2005 Report on Confidential Enquiries into Maternal Deaths in the UK, and 0.973 (95% CI 0.957-0.989) for the non-obstetric National Early Warning Score. This highlights that the new clinical obstetric early warning score has an excellent ability to discriminate survivors from non-survivors in this critical care data set. Further work is needed to validate our new clinical early warning score externally in the obstetric ward environment.}, } @article {pmid23485227, year = {2013}, author = {Berry, DM and Kaylor, MB and Church, J and Campbell, K and McMillin, T and Wamsley, R}, title = {Caritas and job environment: a replication of Persky et al.}, journal = {Contemporary nurse}, volume = {43}, number = {2}, pages = {237-243}, doi = {10.5172/conu.2013.43.2.237}, pmid = {23485227}, issn = {1037-6178}, mesh = {Midwestern United States ; *Nursing ; *Workplace ; }, abstract = {The purpose of this study was to replicate and expand on Persky, Nelson, Watson, and Bent (2008) study of characteristics related to nurses who were effective in Watson's Caritas framework. Previous research suggests that poorer work environments are associated with higher levels of caring. This surprising finding warrants further investigation. Registered nurses were recruited from a mid-sized community-based hospital in the Midwest portion of the United States of America (N = 20). Each completed the health environment survey (HES). Ten patients that had received primary care from the nurse completed the caring factors survey (CFS). Two hundred nurse/patient dyads were used to determine the relationship between the CFS and HES. Six of the 13 HES scales were positively associated with CFS scores. As nurses' positive perceptions of the work environment increased, patients' perceptions of caring increased. Our findings contrast Persky et al.'s. Further research is needed examining factors influencing the relationship between job environment and patient perceptions of caring.}, } @article {pmid23475742, year = {2013}, author = {Conley, D and Rauscher, E}, title = {Genetic interactions with prenatal social environment: effects on academic and behavioral outcomes.}, journal = {Journal of health and social behavior}, volume = {54}, number = {1}, pages = {109-127}, doi = {10.1177/0022146512473758}, pmid = {23475742}, issn = {2150-6000}, support = {P01-HD31921/HD/NICHD NIH HHS/United States ; }, mesh = {Adolescent ; Adolescent Behavior/*psychology ; Adult ; Alleles ; Depression/genetics/psychology ; Educational Status ; Female ; *Gene-Environment Interaction ; Humans ; Male ; Monoamine Oxidase/genetics ; Pregnancy ; Prenatal Exposure Delayed Effects/genetics/*psychology ; Promoter Regions, Genetic ; Receptors, Dopamine D2/genetics ; Serotonin Plasma Membrane Transport Proteins/genetics ; *Social Environment ; Surveys and Questionnaires ; Twins/genetics/psychology ; }, abstract = {Numerous studies report gene-environment interactions, suggesting that specific alleles have different effects on social outcomes depending on environment. In all these studies, however, environmental conditions are potentially endogenous to unmeasured genetic characteristics. That is, it could be that the observed interaction effects actually reflect underlying genetic tendencies that lead individuals into certain environments. What is critical to move this literature forward is random environmental variation that we know is not correlated with innate characteristics of subjects. We exploit a natural experiment that randomizes a particular stressor-birth weight discordance within twin pairs-to address this challenge and ask: Do random differences in early environment (prenatal nutrition) moderate genetic effects on depression, delinquency, or GPA? Using Add Health data, the only consistently significant allele-birth weight interaction we reveal works in the opposite direction of Caspi et al.'s classic finding regarding the interaction of maltreatment with genetic variation in the serotonin transporter promoter. Less robust interactions found for DRD2 and MAOA are consistent with this pattern that reverses prior findings. These results do not necessarily overturn existing research but support our methodological point that gene-environment research must address endogeneity.}, } @article {pmid23471247, year = {2013}, author = {Bassingthwaighte, JB and Chinn, TM}, title = {Reexamining Michaelis-Menten enzyme kinetics for xanthine oxidase.}, journal = {Advances in physiology education}, volume = {37}, number = {1}, pages = {37-48}, pmid = {23471247}, issn = {1522-1229}, support = {EB-08407/EB/NIBIB NIH HHS/United States ; R01 EB001973/EB/NIBIB NIH HHS/United States ; T15 HL088516/HL/NHLBI NIH HHS/United States ; R01 EB008407/EB/NIBIB NIH HHS/United States ; T32 HL007403/HL/NHLBI NIH HHS/United States ; T15-HL-088516/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; Cattle ; Kinetics ; *Models, Biological ; Reproducibility of Results ; Xanthine Oxidase/*chemistry/*pharmacokinetics ; }, abstract = {Abbreviated expressions for enzyme kinetic expressions, such as the Michaelis-Menten (M-M) equations, are based on the premise that enzyme concentrations are low compared with those of the substrate and product. When one does progress experiments, where the solute is consumed during conversion to form a series of products, the idealized conditions are violated. Here, we analyzed data of xanthine oxidase in vitro from Escribano et al. (Biochem J 254: 829, 1988) on two conversions in series, hypoxanthine to xanthine to uric acid. Analyses were done using four models: standard irreversible M-M reactions (model 1), Escribano et al.'s M-M forward reaction expressions with product inhibition (model 2), fully reversible M-M equations (model 3), and standard differential equations allowing forward and backward reactions with mass balance accounting for binding (model 4). The results showed that the need for invoking product inhibition vanishes with more complete analyses. The reactions were not quite irreversible, so the backward reaction had a small effect. Even though the enzyme concentration was only 1-2% of the initial substrate concentrations, accounting for the fraction of solutes bound to the enzyme did influence the parameter estimates, but in this case, the M-M model overestimated Michaelis constant values by only about one-third. This article also presents the research and models in a reproducible and publicly available form.}, } @article {pmid23466410, year = {2013}, author = {Stöcker, W and Probst, C and Komorowski, L}, title = {Reply to Dr. Roggenbuck et al.'s letter.}, journal = {Journal of Crohn's & colitis}, volume = {7}, number = {7}, pages = {e275-6}, doi = {10.1016/j.crohns.2013.02.003}, pmid = {23466410}, issn = {1876-4479}, mesh = {Autoantibodies/*immunology ; Colitis, Ulcerative/*immunology ; Crohn Disease/*immunology ; GPI-Linked Proteins/*immunology ; Humans ; *Immune Tolerance ; Membrane Proteins/*immunology ; }, } @article {pmid23454611, year = {2013}, author = {Zheng, M and Li, X and Guo, L}, title = {Algorithms of GPU-enabled reactive force field (ReaxFF) molecular dynamics.}, journal = {Journal of molecular graphics & modelling}, volume = {41}, number = {}, pages = {1-11}, doi = {10.1016/j.jmgm.2013.02.001}, pmid = {23454611}, issn = {1873-4243}, mesh = {*Algorithms ; Computer Graphics ; Imaging, Three-Dimensional ; Models, Chemical ; *Molecular Dynamics Simulation ; Quantum Theory ; *Software ; }, abstract = {Reactive force field (ReaxFF), a recent and novel bond order potential, allows for reactive molecular dynamics (ReaxFF MD) simulations for modeling larger and more complex molecular systems involving chemical reactions when compared with computation intensive quantum mechanical methods. However, ReaxFF MD can be approximately 10-50 times slower than classical MD due to its explicit modeling of bond forming and breaking, the dynamic charge equilibration at each time-step, and its one order smaller time-step than the classical MD, all of which pose significant computational challenges in simulation capability to reach spatio-temporal scales of nanometers and nanoseconds. The very recent advances of graphics processing unit (GPU) provide not only highly favorable performance for GPU enabled MD programs compared with CPU implementations but also an opportunity to manage with the computing power and memory demanding nature imposed on computer hardware by ReaxFF MD. In this paper, we present the algorithms of GMD-Reax, the first GPU enabled ReaxFF MD program with significantly improved performance surpassing CPU implementations on desktop workstations. The performance of GMD-Reax has been benchmarked on a PC equipped with a NVIDIA C2050 GPU for coal pyrolysis simulation systems with atoms ranging from 1378 to 27,283. GMD-Reax achieved speedups as high as 12 times faster than Duin et al.'s FORTRAN codes in Lammps on 8 CPU cores and 6 times faster than the Lammps' C codes based on PuReMD in terms of the simulation time per time-step averaged over 100 steps. GMD-Reax could be used as a new and efficient computational tool for exploiting very complex molecular reactions via ReaxFF MD simulation on desktop workstations.}, } @article {pmid23445598, year = {2013}, author = {Rochat, P and Robbins, E}, title = {Ego function of morality and developing tensions that are "within".}, journal = {The Behavioral and brain sciences}, volume = {36}, number = {1}, pages = {98-99}, doi = {10.1017/S0140525X12000854}, pmid = {23445598}, issn = {1469-1825}, mesh = {*Choice Behavior ; Female ; Humans ; Male ; *Marriage ; *Morals ; *Sexual Partners ; }, abstract = {We applaud Baumard et al.’s mutualistic account of morality but detect circularity in their articulation of how morality emerged. Contra the authors, we propose that mutualism might account for a sensitivity to convention (the ways things are done within a group) rather than for a sense of fairness. An ontogenetic perspective better captures the complexity of what it means to be moral.}, } @article {pmid23445587, year = {2013}, author = {Fessler, DM and Holbrook, C}, title = {Baumard et al.'s moral markets lack market dynamics.}, journal = {The Behavioral and brain sciences}, volume = {36}, number = {1}, pages = {89-90}, doi = {10.1017/S0140525X12000945}, pmid = {23445587}, issn = {1469-1825}, mesh = {*Choice Behavior ; Female ; Humans ; Male ; *Marriage ; *Morals ; *Sexual Partners ; }, abstract = {Market models are indeed indispensable to understanding the evolution of cooperation and its emotional substrates. Unfortunately, Baumard et al. eschew market thinking in stressing the supposed invariance of moral/cooperative behavior across circumstances. To the contrary, humans display contingent morality/cooperation, and these shifts are best accounted for by market models of partner choice for mutually beneficial collaboration.}, } @article {pmid23445583, year = {2013}, author = {Clark, MS and Boothby, E}, title = {A strange(r) analysis of morality: a consideration of relational context and the broader literature is needed.}, journal = {The Behavioral and brain sciences}, volume = {36}, number = {1}, pages = {85-86}, doi = {10.1017/S0140525X12000751}, pmid = {23445583}, issn = {1469-1825}, mesh = {*Choice Behavior ; Female ; Humans ; Male ; *Marriage ; *Morals ; *Sexual Partners ; }, abstract = {Baumard et al.’s definition of morality is narrow and their review of empirical work on human cooperation is limited, focusing only on economic games, almost always involving strangers. We suggest that theorizing about mutualisms will benefit from considering extant empirical behavioral research far more broadly and especially from taking relational context into account.}, } @article {pmid23445579, year = {2013}, author = {Binmore, K}, title = {Modeling justice as a natural phenomenon.}, journal = {The Behavioral and brain sciences}, volume = {36}, number = {1}, pages = {82-83}, doi = {10.1017/S0140525X12000933}, pmid = {23445579}, issn = {1469-1825}, mesh = {*Choice Behavior ; Female ; Humans ; Male ; *Marriage ; *Morals ; *Sexual Partners ; }, abstract = {Among other things, Baumard et al.’s “A Mutualistic Approach to Morality” considers the enforcement and establishment of moral norms, the interpersonal comparison of welfare, and the structure of fairness norms. This commentary draws attention to the relevance of the game theory literature to the first and second topic, and the social psychology literature to the third topic.}, } @article {pmid23415168, year = {2013}, author = {Laba, TL and Bleasel, J and Brien, JA and Cass, A and Howard, K and Peiris, D and Redfern, J and Salam, A and Usherwood, T and Jan, S}, title = {Strategies to improve adherence to medications for cardiovascular diseases in socioeconomically disadvantaged populations: a systematic review.}, journal = {International journal of cardiology}, volume = {167}, number = {6}, pages = {2430-2440}, doi = {10.1016/j.ijcard.2013.01.049}, pmid = {23415168}, issn = {1874-1754}, mesh = {Cardiovascular Diseases/*drug therapy/*economics/ethnology ; Cost-Benefit Analysis/methods ; Humans ; *Medication Adherence/ethnology ; Socioeconomic Factors ; *Vulnerable Populations/ethnology ; }, abstract = {Medication non-adherence poses a major barrier to reducing cardiovascular disease (CVD) burden globally, and is increasingly recognised as a socioeconomically determined problem. Strategies promoting CVD medication adherence appear of moderate effectiveness and cost-effectiveness. Potentially, 'one-size-fits-all' measures are ill-equipped to address heterogeneous adherence behaviour between social groups. This review aims to determine the effects of strategies to improve adherence to CVD-related medications in socioeconomically disadvantaged groups. Randomised/quasi-randomised controlled trials (1996-June 2012, English), testing strategies to increase adherence to CVD-related medications prescribed to adult patients who may experience health inequity (place of residence, occupation, education, or socioeconomic position) were reviewed. 772 abstracts were screened, 111 full-text articles retrieved, and 16 full-text articles reporting on 14 studies, involving 7739 patients (age range 41-66 years), were included. Methodological and clinical heterogeneity precluded quantitative data synthesis. Studies were thematically grouped by targeted outcomes; underlying interventions and policies were classified using Michie et al.'s Behaviour Change Wheel. Contrasting with patient or physician/practice strategies, those simultaneously directed at patients and physicians/practices resulted in statistically significant improvements in relative adherence (16-169%). Comparative cost and cost-effectiveness analyses from three studies did not find cost-saving or cost-effective strategies. Unlike much current evidence in general populations, promising evidence exists about what strategies improve adherence in disadvantaged groups. These strategies were generally complex: simultaneously targeting patients and physicians; addressing social, financial, and treatment-related adherence barriers; and supported by broader guidelines, regulatory and communication-based policies. Given their complexity and potential resource implications, comprehensive process evaluations and cost and cost-effectiveness evidence are urgently needed.}, } @article {pmid23410065, year = {2013}, author = {Ogden, RS}, title = {The effect of facial attractiveness on temporal perception.}, journal = {Cognition & emotion}, volume = {27}, number = {7}, pages = {1292-1304}, doi = {10.1080/02699931.2013.769426}, pmid = {23410065}, issn = {1464-0600}, mesh = {Adolescent ; Adult ; Attention ; *Beauty ; *Face ; Female ; Humans ; *Time Perception ; }, abstract = {Previous research suggests that feelings of fear, dislike, shame and sadness affect our perception of duration (Droit-Volet et al., 2004; Gil et al., 2009). The current study sought to expand our understanding of the variables which moderate temporal perception by examining whether the attractiveness of a face influenced its perceived duration. Participants completed a verbal estimation task in which they judged the duration of attractive, unattractive and neutral faces. The results showed that participants underestimated the duration of unattractive faces relative to attractive and neutral faces. Estimates of unattractive faces were also less accurate than those of the attractive and neutral faces. The results are consistent with Gil et al.'s (2009) suggestion that the duration of disliked stimuli are underestimated relative to liked and neutral stimuli because they detract attention from temporal perception. Analysis of the slope and intercept of the estimation gradients supports Zakay and Block's (1997) suggestion that reduced attention to time results in a multiplicative underestimation of duration.}, } @article {pmid23408279, year = {2013}, author = {Petras, H and Buckley, JA and Leoutsakos, JM and Stuart, EA and Ialongo, NS}, title = {The use of multiple versus single assessment time points to improve screening accuracy in identifying children at risk for later serious antisocial behavior.}, journal = {Prevention science : the official journal of the Society for Prevention Research}, volume = {14}, number = {5}, pages = {423-436}, pmid = {23408279}, issn = {1573-6695}, support = {P30 MH066247/MH/NIMH NIH HHS/United States ; T-32 MH 18834/MH/NIMH NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Antisocial Personality Disorder/diagnosis/*prevention & control ; Child ; Female ; Humans ; Male ; *Psychological Tests ; ROC Curve ; Risk Assessment ; Young Adult ; }, abstract = {Guided by Kraemer et al.'s (Psychological Methods, 3:257-271, 1999) framework for measuring the potency of risk factors, we sought to improve on the classification accuracy reported in Petras et al. (Journal of the American Academy of Child and Adolescent Psychiatry 43:88-96, 2004a) and Petras et al. (Journal of the American Academy of Child and Adolescent Psychiatry 44:790-797, 2005) by using multiple as opposed to single point in time assessments of early aggressive and disruptive behavior in the classification of youth who would likely benefit from targeted preventive interventions. Different from Petras et al. (2004a, 2005), the outcome used in this study included serious antisocial behavior in young adulthood as well as in adolescence. Among males, the use of multiple time points did not yield greater classification accuracy than the highest single time points, that is, third and fifth grades. For females, although fifth grade represented the best single time point in terms of classification accuracy, no significant association was found between earlier time points and the later outcome, rendering a test of the multiple time points hypothesis moot. The findings presented in this study have strong implications for the design of targeted intervention for violence prevention, indicating that the screening quality based on aggression ratings during the elementary years is rather modest, particularly for females.}, } @article {pmid23404628, year = {2012}, author = {Kolossa, A and Fingscheidt, T and Wessel, K and Kopp, B}, title = {A model-based approach to trial-by-trial p300 amplitude fluctuations.}, journal = {Frontiers in human neuroscience}, volume = {6}, number = {}, pages = {359}, pmid = {23404628}, issn = {1662-5161}, abstract = {It has long been recognized that the amplitude of the P300 component of event-related brain potentials is sensitive to the degree to which eliciting stimuli are surprising to the observers (Donchin, 1981). While Squires et al. (1976) showed and modeled dependencies of P300 amplitudes from observed stimuli on various time scales, Mars et al. (2008) proposed a computational model keeping track of stimulus probabilities on a long-term time scale. We suggest here a computational model which integrates prior information with short-term, long-term, and alternation-based experiential influences on P300 amplitude fluctuations. To evaluate the new model, we measured trial-by-trial P300 amplitude fluctuations in a simple two-choice response time task, and tested the computational models of trial-by-trial P300 amplitudes using Bayesian model evaluation. The results reveal that the new digital filtering (DIF) model provides a superior account of the trial-by-trial P300 amplitudes when compared to both Squires et al.'s (1976) model, and Mars et al.'s (2008) model. We show that the P300-generating system can be described as two parallel first-order infinite impulse response (IIR) low-pass filters and an additional fourth-order finite impulse response (FIR) high-pass filter. Implications of the acquired data are discussed with regard to the neurobiological distinction between short-term, long-term, and working memory as well as from the point of view of predictive coding models and Bayesian learning theories of cortical function.}, } @article {pmid23398770, year = {2013}, author = {Rubens, D and Davis, A and McAlpine, J and Fleming, P and Blair, P and Ewer, A}, title = {Letter of Response to Chan et al.'s paper regarding Rhode Island Newborn Hearing screening finding and the Sudden Infant Death Syndrome.}, journal = {International journal of pediatric otorhinolaryngology}, volume = {77}, number = {4}, pages = {613-614}, doi = {10.1016/j.ijporl.2012.12.028}, pmid = {23398770}, issn = {1872-8464}, mesh = {Female ; Humans ; Male ; *Otoacoustic Emissions, Spontaneous ; Sudden Infant Death/*epidemiology ; }, } @article {pmid23396427, year = {2013}, author = {Gildas Comlan Zohoun, A and Moket, D and El Hamzaoui, S}, title = {[Prevalence of Acinetobacter baumannii and Pseudomonas aeruginosa isolates resistant to imipenem by production of metallo-β-lactamases in Rabat Military Teaching Hospital Mohammed V].}, journal = {Annales de biologie clinique}, volume = {71}, number = {1}, pages = {27-30}, doi = {10.1684/abc.2012.0778}, pmid = {23396427}, issn = {1950-6112}, mesh = {Acinetobacter Infections/*epidemiology/microbiology ; *Acinetobacter baumannii/enzymology/isolation & purification/metabolism ; Anti-Bacterial Agents/*therapeutic use ; *Drug Resistance, Bacterial ; Female ; Hospitals, Military/statistics & numerical data ; Hospitals, Teaching/statistics & numerical data ; Humans ; Imipenem/*therapeutic use ; Male ; Morocco/epidemiology ; Prevalence ; Pseudomonas Infections/*epidemiology/microbiology ; *Pseudomonas aeruginosa/enzymology/isolation & purification/metabolism ; beta-Lactamases/*metabolism ; }, abstract = {We studied the production of metallo-β-lactamases (MBL) in Acinetobacter baumannii and Pseudomonas aeruginosa strains resistant to imipenem at the Rabat Mohammed V military teaching hospital, according to Yong et al.'s method, using a sterilized solution of EDTA 0.5 M pH 8. One hundred and five bacterial strains (48 A. baumannii and 57 P. aeruginosa) were identified. 45 (42.9%) with 34 A. baumannii and 11 P. aeruginosa were resistant to imipenem. The prevalence of MBL producing strains was 22.2% (10/45). The existence of this isolates resistant to imipenem by producing metallo-β-lactamases is an emerging public health problem. It is necessary to implemente infection control programs to avoid spreading of multidrug resistant bacteria.}, } @article {pmid23392626, year = {2013}, author = {Odelu, V and Das, AK and Goswami, A}, title = {An effective and secure key-management scheme for hierarchical access control in E-medicine system.}, journal = {Journal of medical systems}, volume = {37}, number = {2}, pages = {9920}, pmid = {23392626}, issn = {1573-689X}, mesh = {Access to Information ; Algorithms ; *Computer Security ; *Electronic Health Records ; *Software ; }, abstract = {Recently several hierarchical access control schemes are proposed in the literature to provide security of e-medicine systems. However, most of them are either insecure against 'man-in-the-middle attack' or they require high storage and computational overheads. Wu and Chen proposed a key management method to solve dynamic access control problems in a user hierarchy based on hybrid cryptosystem. Though their scheme improves computational efficiency over Nikooghadam et al.'s approach, it suffers from large storage space for public parameters in public domain and computational inefficiency due to costly elliptic curve point multiplication. Recently, Nikooghadam and Zakerolhosseini showed that Wu-Chen's scheme is vulnerable to man-in-the-middle attack. In order to remedy this security weakness in Wu-Chen's scheme, they proposed a secure scheme which is again based on ECC (elliptic curve cryptography) and efficient one-way hash function. However, their scheme incurs huge computational cost for providing verification of public information in the public domain as their scheme uses ECC digital signature which is costly when compared to symmetric-key cryptosystem. In this paper, we propose an effective access control scheme in user hierarchy which is only based on symmetric-key cryptosystem and efficient one-way hash function. We show that our scheme reduces significantly the storage space for both public and private domains, and computational complexity when compared to Wu-Chen's scheme, Nikooghadam-Zakerolhosseini's scheme, and other related schemes. Through the informal and formal security analysis, we further show that our scheme is secure against different attacks and also man-in-the-middle attack. Moreover, dynamic access control problems in our scheme are also solved efficiently compared to other related schemes, making our scheme is much suitable for practical applications of e-medicine systems.}, } @article {pmid23387518, year = {2013}, author = {Welsh, TN and Kiernan, D and Neyedli, HF and Ray, M and Pratt, J and Potruff, A and Weeks, DJ}, title = {Joint Simon effects in extrapersonal space.}, journal = {Journal of motor behavior}, volume = {45}, number = {1}, pages = {1-5}, doi = {10.1080/00222895.2012.746635}, pmid = {23387518}, issn = {1940-1027}, mesh = {*Choice Behavior ; *Cooperative Behavior ; Female ; Humans ; Male ; *Reaction Time ; *Signal Detection, Psychological ; }, abstract = {Numerous studies have revealed that when people sit next to each other and complete separate parts of a Simon task, response times are shorter when the participants' stimulus appears in front of them than when the stimulus appears in the opposite side of space. According to the action co-representation account of this joint Simon effect (JSE), participants represent each other's responses and the compatibility effects emerge because of a set of facilitatory and inhibitory processes that are similar to those that are activated when individuals perform the entire Simon task alone. D. Guagnano, E. Rusconi, and C. A. Umiltà (2010) argued against this account as the sole mechanism based on their finding that a JSE was not observed when participants sat outside of each other's peripersonal space. Notably, the task in the Guagnano et al.'s was a modified version of the conventional JSE task designed to increase the independence of the partners. Here, we reconsider the arguments of Guagnano et al. and report a study in which the authors failed to replicate their key finding. Considering the extant JSE literature, we conclude that the null effect in Guagnano et al.'s study may be an anomaly and that co-representation remains a leading candidate for the critical process underlying JSEs.}, } @article {pmid23382227, year = {2013}, author = {Belot, M and Crawford, VP and Heyes, C}, title = {Players of Matching Pennies automatically imitate opponents' gestures against strong incentives.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {110}, number = {8}, pages = {2763-2768}, pmid = {23382227}, issn = {1091-6490}, abstract = {There is a large body of evidence of apparently spontaneous mimicry in humans. This phenomenon has been described as "automatic imitation" and attributed to a mirror neuron system, but there is little direct evidence that it is involuntary rather than intentional. Cook et al. supplied the first such evidence in a unique strategic game design that gave all subjects a pecuniary incentive to avoid imitation [Cook R, Bird G, Lünser G, Huck S, Heyes C (2012) Proc Biol Sci 279(1729):780-786]. Subjects played Rock-Paper-Scissors repeatedly in matches between fixed pairs, sometimes with one and sometimes with both subjects blindfolded. The frequency of draws in the blind-blind condition was at chance, but in the blind-sighted condition it was significantly higher, suggesting automatic imitation had occurred. Automatic imitation would raise novel issues concerning how strategic interactions are modeled in game theory and social science; however, inferring automatic imitation requires significant incentives to avoid it, and subjects' incentives were less than 3 US cents per 60-game match. We replaced Cook et al.'s Rock-Paper-Scissors with a Matching Pennies game, which allows far stronger incentives to avoid imitation for some subjects, with equally strong incentives to imitate for others. Our results are important in providing evidence of automatic imitation against significant incentives. That some of our subjects had incentives to imitate also enables us clearly to distinguish intentional responding from automatic imitation, and we find evidence that both occur. Thus, our results strongly confirm the occurrence of automatic imitation, and illuminate the way that automatic and intentional processes interact in a strategic context.}, } @article {pmid23375627, year = {2013}, author = {Statucka, M and Walder, DJ}, title = {Efficacy of social cognition remediation programs targeting facial affect recognition deficits in schizophrenia: a review and consideration of high-risk samples and sex differences.}, journal = {Psychiatry research}, volume = {206}, number = {2-3}, pages = {125-139}, doi = {10.1016/j.psychres.2012.12.005}, pmid = {23375627}, issn = {1872-7123}, mesh = {Affect ; Face ; *Facial Expression ; Female ; Humans ; Male ; *Pattern Recognition, Visual ; Perceptual Disorders/psychology/*therapy ; Schizophrenia/*therapy ; *Schizophrenic Psychology ; Sex Factors ; Social Adjustment ; *Social Perception ; Treatment Outcome ; }, abstract = {Schizophrenia patients suffer from significant social functioning deficits. Social cognition, particularly facial affect recognition (FAR), is an important predictor of functional outcome. Recently, investigators developed numerous social cognition remediation programs targeting FAR deficits with the goal of improving social functioning and quality of life in schizophrenia patients. This article builds on Horan et al.'s (2008) comprehensive review and Kurtz and Richardson's (2012) meta-analysis of a broad range of social cognition remediations, by systematically reviewing efficacy of empirically based remediations in schizophrenia specifically targeting FAR (across 23 studies), and their potential functional benefits. We describe each FAR-based social cognition remediation program, which may aid clinical scientists and clinicians in selecting programs for further study and practice. We critically evaluate limitations of FAR remediation programs and applications. Our review concludes FAR remediation programs are strongly efficacious in improving FAR performance and functional status in schizophrenia. Importantly, we provide rationale for and recommend that future research consider (as yet underexplored) sexual dimorphisms in FAR remediation effects, and examine FAR remediation in clinical high-risk for psychosis populations. The goal is to mitigate deficits, perhaps hinder illness onset, and individually tailor treatments across the psychosis continuum in a way that maximally aids those in greatest need.}, } @article {pmid23351930, year = {2013}, author = {Del-Monte, J and Capdevielle, D and Gély-Nargeot, MC and Yazbek, H and Pupier, F and Boulenger, JP and Raffard, S}, title = {[Evolution of the concept of apathy: the need for a multifactorial approach in schizophrenia].}, journal = {L'Encephale}, volume = {39 Suppl 1}, number = {}, pages = {S57-63}, doi = {10.1016/j.encep.2012.11.005}, pmid = {23351930}, issn = {0013-7006}, mesh = {Activities of Daily Living/psychology ; *Apathy/physiology ; Basal Ganglia/physiopathology ; Humans ; Limbic System/physiopathology ; Neural Pathways/physiopathology ; Prefrontal Cortex/physiopathology ; Prognosis ; Psychiatric Status Rating Scales ; Rehabilitation, Vocational ; Schizophrenia/*diagnosis/physiopathology/rehabilitation ; *Schizophrenic Psychology ; }, abstract = {BACKGROUND: Schizophrenia is a chronic and severe mental illness that affects over 1% of the population, characterized by multiple symptom dimensions. One of this class of symptoms, "negative symptoms", have received more attention over the last few years. Negative symptoms, including among others blunted affect, withdrawal or apathy, are particularly important for recovery and are associated with negative functional outcomes, such as inability to get an employment and conduct normal daily living activities. While positive symptoms are usually treated by antipsychotic drugs, negative symptoms are usually persistent, which indicates the need for better treatment. The aim of this article is to highlight recent scientific progress on apathy and to explore current multidimensional approaches of this concept in schizophrenia. Apathy is a symptom frequently encountered in schizophrenia and in many neurological disorders. Therefore, it can be regarded as a transnosographic symptom.

LITERATURE FINDINGS: A long time considered as a loss of motivation (psychological concept hard to define), recent descriptive and etiological models have proposed to consider apathy as a multidimensional phenomenon. Marin et al., have proposed a model of apathy in reference to the motivation concept. Marin et al.'s apathy model is composed of three dimensions: firstly, cognitive dimension, secondly, sensory-motor dimension and thirdly, affective dimension. These authors propose to differentiate "apathy syndrome" from "apathy symptom". "Apathy syndrome" resulting from a lack of motivation whereas "apathy symptom" results from cognitive and/or emotional/affective disorders. In addition, Marin et al. propose that apathy syndrome corresponds to the "lack of motivation" not attributable to diminished level of consciousness, cognitive impairment or emotional distress. Following this proposal, Levy and Dubois propose to define apathy as a quantitative reduction of self-generated, voluntary and purposeful behaviors. It is therefore observable and can be quantified. Levy and Dubois have proposed an apathy model considering: firstly, apathy as a syndrome related to reduction in goal-directed behaviors; secondly, anatomically, apathy can be secondary to dysfunctions or lesions of the prefrontal cortex. Since the prefrontal cortex is functionally and anatomically heterogeneous, subtypes of apathy occur in diseases affecting the basal ganglia, because these diseases disrupt associative and limbic pathways from/to the prefrontal cortex; thirdly, from a pathophysiological point of view, apathy may be explained by the impact of lesions or dysfunctions of the basal ganglia, because these lesions or dysfunctions lead to a loss of temporal and spatial focalization, both of which result in a diminished extraction of the relevant signal within the frontal cortex, thereby inhibiting the capacity of the frontal cortex to select, initiate, maintain and shift programs of action.}, } @article {pmid23345391, year = {2013}, author = {Meier, PS and Meng, Y and Holmes, J and Baumberg, B and Purshouse, R and Hill-McManus, D and Brennan, A}, title = {Adjusting for unrecorded consumption in survey and per capita sales data: quantification of impact on gender- and age-specific alcohol-attributable fractions for oral and pharyngeal cancers in Great Britain.}, journal = {Alcohol and alcoholism (Oxford, Oxfordshire)}, volume = {48}, number = {2}, pages = {241-249}, doi = {10.1093/alcalc/agt001}, pmid = {23345391}, issn = {1464-3502}, support = {G000043/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Adolescent ; Adult ; Age Factors ; Aged ; Alcohol Drinking/economics/*epidemiology ; *Alcoholic Beverages/economics ; Child ; *Commerce/economics ; Cross-Sectional Studies ; Female ; Humans ; Male ; Middle Aged ; Mouth Neoplasms/diagnosis/economics/*epidemiology ; Pharyngeal Neoplasms/diagnosis/economics/*epidemiology ; Sex Factors ; United Kingdom/epidemiology ; Young Adult ; }, abstract = {AIMS: Large discrepancies are typically found between per capita alcohol consumption estimated via survey data compared with sales, excise or production figures. This may lead to significant inaccuracies when calculating levels of alcohol-attributable harms. Using British data, we demonstrate an approach to adjusting survey data to give more accurate estimates of per capita alcohol consumption.

METHODS: First, sales and survey data are adjusted to account for potential biases (e.g. self-pouring, under-sampled populations) using evidence from external data sources. Secondly, survey and sales data are aligned using different implementations of Rehm et al.'s method [in (2010) Statistical modeling of volume of alcohol exposure for epidemiological studies of population health: the US example. Pop Health Metrics 8, 1-12]. Thirdly, the impact of our approaches is tested by using our revised survey dataset to calculate alcohol-attributable fractions (AAFs) for oral and pharyngeal cancers.

RESULTS: British sales data under-estimate per capita consumption by 8%, primarily due to illicit alcohol. Adjustments to survey data increase per capita consumption estimates by 35%, primarily due to under-sampling of dependent drinkers and under-estimation of home-poured spirits volumes. Before aligning sales and survey data, the revised survey estimate remains 22% lower than the revised sales estimate. Revised AAFs for oral and pharyngeal cancers are substantially larger with our preferred method for aligning data sources, yielding increases in an AAF from the original survey dataset of 0.47-0.60 (males) and 0.28-0.35 (females).

CONCLUSION: It is possible to use external data sources to adjust survey data to reduce the under-estimation of alcohol consumption and then account for residual under-estimation using a statistical calibration technique. These revisions lead to markedly higher estimated levels of alcohol-attributable harm.}, } @article {pmid23345091, year = {2013}, author = {Cao, T and Zhai, J}, title = {Improved dynamic ID-based authentication scheme for telecare medical information systems.}, journal = {Journal of medical systems}, volume = {37}, number = {2}, pages = {9912}, pmid = {23345091}, issn = {1573-689X}, mesh = {*Computer Security ; *Confidentiality ; *Electronic Health Records ; *Patient Identification Systems ; Radio Frequency Identification Device ; *Telemedicine ; User-Computer Interface ; }, abstract = {In order to protect users' identity privacy, Chen et al. proposed an efficient dynamic ID-based authentication scheme for telecare medical information systems. However, Chen et al.'s scheme has some weaknesses. In Chen et al.'s scheme, an attacker can track a user by a linkability attack or an off-line identity guessing attack. Chen et al.'s scheme is also vulnerable to an off-line password guessing attack and an undetectable on-line password guessing attack when user's smart card is stolen. In server side, Chen et al.'s scheme needs large computational load to authentication a legal user or reject an illegal user. To remedy the weaknesses in Chen et al.'s scheme, we propose an improved smart card based password authentication scheme. Our analysis shows that the improved scheme can overcome the weaknesses in Chen et al.'s scheme.}, } @article {pmid23324495, year = {2013}, author = {Coyne, JC and Kwakkenbos, L}, title = {Triple P-Positive Parenting programs: the folly of basing social policy on underpowered flawed studies.}, journal = {BMC medicine}, volume = {11}, number = {}, pages = {11}, pmid = {23324495}, issn = {1741-7015}, mesh = {Humans ; *Parenting ; }, abstract = {Wilson et al. provided a valuable systematic and meta-analytic review of the Triple P-Positive Parenting program in which they identified substantial problems in the quality of available evidence. Their review largely escaped unscathed after Sanders et al.'s critical commentary. However, both of these sources overlook the most serious problem with the Triple P literature, namely, the over-reliance on positive but substantially underpowered trials. Such trials are particularly susceptible to risks of bias and investigator manipulation of apparent results. We offer a justification for the criterion of no fewer than 35 participants in either the intervention or control group. Applying this criterion, 19 of the 23 trials identified by Wilson et al. were eliminated. A number of these trials were so small that it would be statistically improbable that they would detect an effect even if it were present. We argued that clinicians and policymakers implementing Triple P programs incorporate evaluations to ensure that goals are being met and resources are not being squandered.Please see related articles http://www.biomedcentral.com/1741-7015/10/130 and http://www.biomedcentral.com/1741-7015/10/145.}, } @article {pmid23321972, year = {2013}, author = {Xie, Q and Zhang, J and Dong, N}, title = {Robust anonymous authentication scheme for telecare medical information systems.}, journal = {Journal of medical systems}, volume = {37}, number = {2}, pages = {9911}, pmid = {23321972}, issn = {1573-689X}, mesh = {*Computer Security ; *Confidentiality ; *Electronic Health Records ; *Patient Identification Systems ; Radio Frequency Identification Device ; *Telemedicine ; User-Computer Interface ; }, abstract = {Patient can obtain sorts of health-care delivery services via Telecare Medical Information Systems (TMIS). Authentication, security, patient's privacy protection and data confidentiality are important for patient or doctor accessing to Electronic Medical Records (EMR). In 2012, Chen et al. showed that Khan et al.'s dynamic ID-based authentication scheme has some weaknesses and proposed an improved scheme, and they claimed that their scheme is more suitable for TMIS. However, we show that Chen et al.'s scheme also has some weaknesses. In particular, Chen et al.'s scheme does not provide user's privacy protection and perfect forward secrecy, is vulnerable to off-line password guessing attack and impersonation attack once user's smart card is compromised. Further, we propose a secure anonymity authentication scheme to overcome their weaknesses even an adversary can know all information stored in smart card.}, } @article {pmid23321959, year = {2013}, author = {Jiang, Q and Ma, J and Ma, Z and Li, G}, title = {A privacy enhanced authentication scheme for telecare medical information systems.}, journal = {Journal of medical systems}, volume = {37}, number = {1}, pages = {9897}, pmid = {23321959}, issn = {1573-689X}, mesh = {*Computer Security ; *Confidentiality ; Humans ; Information Systems/*organization & administration/standards ; Telemedicine/*organization & administration/standards ; }, abstract = {The telecare medical information system (TMIS) aims to establish telecare services and enable the public to access medical services or medical information at remote sites. Authentication and key agreement is essential to ensure data integrity, confidentiality, and availability for TMIS. Most recently, Chen et al. proposed an efficient and secure dynamic ID-based authentication scheme for TMIS, and claimed that their scheme achieves user anonymity. However, we observe that Chen et al.'s scheme achieves neither anonymity nor untraceability, and is subject to the identity guessing attack and tracking attack. In order to protect user privacy, we propose an enhanced authentication scheme which achieves user anonymity and untraceablity. It is a secure and efficient authentication scheme with user privacy preservation which is practical for TMIS.}, } @article {pmid23317679, year = {2013}, author = {Kelty-Stephen, DG and Dixon, JA}, title = {Temporal correlations in postural sway moderate effects of stochastic resonance on postural stability.}, journal = {Human movement science}, volume = {32}, number = {1}, pages = {91-105}, doi = {10.1016/j.humov.2012.08.006}, pmid = {23317679}, issn = {1872-7646}, mesh = {Adult ; Aged ; Aging/*physiology ; Biomechanical Phenomena/physiology ; Female ; Humans ; Individuality ; Male ; Nonlinear Dynamics ; Postural Balance/*physiology ; Reference Values ; Statistics as Topic ; Stochastic Processes ; Subliminal Stimulation ; Vibration ; Weight-Bearing/*physiology ; }, abstract = {The present work documents reanalysis of previous research by Priplata and colleagues (Priplata et al., 2002) into the effects of subthreshold vibratory stimulation to the plantar surface of the foot on postural stability during quiet standing. In stochastic resonance, stimulating a nonlinear system with noise can promote system stability. Stochastic resonance has been proposed to have clinical applications as an intervention that might help to stabilize posture. Insoles designed to stimulate the plantar surface of the foot with uncorrelated white-noise fluctuations have been shown to reduce a number of standard measures of postural variability. An important remaining concern is that the efficacy of stochastic-resonance applications is subject to strong individual differences. Our reanalysis of data from Priplata et al.'s original study provides evidence that effects of uncorrelated fluctuations in subthreshold vibratory stimulation are moderated by temporally correlated fluctuations in postural sway. We suggest how future development might capitalize on this finding to fine-tune existing stochastic-resonance applications to posture.}, } @article {pmid23312109, year = {2013}, author = {Lopez, AM and Bourgois, P and Wenger, LD and Lorvick, J and Martinez, AN and Kral, AH}, title = {Interdisciplinary mixed methods research with structurally vulnerable populations: case studies of injection drug users in San Francisco.}, journal = {The International journal on drug policy}, volume = {24}, number = {2}, pages = {101-109}, pmid = {23312109}, issn = {1873-4758}, support = {R01 DA021627/DA/NIDA NIH HHS/United States ; 1R01DA021100/DA/NIDA NIH HHS/United States ; 5R01DA023377/DA/NIDA NIH HHS/United States ; 5R01DA010164/DA/NIDA NIH HHS/United States ; 5R01DA021627/DA/NIDA NIH HHS/United States ; R01 DA021100/DA/NIDA NIH HHS/United States ; R01 DA023377/DA/NIDA NIH HHS/United States ; R01 DA010164/DA/NIDA NIH HHS/United States ; }, mesh = {Data Collection/*methods ; Drug Users/*psychology ; Ill-Housed Persons/psychology ; Humans ; *Interdisciplinary Studies ; San Francisco/epidemiology ; Substance Abuse, Intravenous/*epidemiology ; Vulnerable Populations/*psychology ; }, abstract = {Research with injection drug users (IDUs) benefits from interdisciplinary theoretical and methodological innovation because drug use is illegal, socially sanctioned and often hidden. Despite the increasing visibility of interdisciplinary, mixed methods research projects with IDUs, qualitative components are often subordinated to quantitative approaches and page restrictions in top addiction journals limit detailed reports of complex data collection and analysis logistics, thus minimizing the fuller scientific potential of genuine mixed methods. We present the methodological logistics and conceptual approaches of four mixed-methods research projects that our interdisciplinary team conducted in San Francisco with IDUs over the past two decades. These projects include combinations of participant-observation ethnography, in-depth qualitative interviewing, epidemiological surveys, photo-documentation, and geographic mapping. We adapted Greene et al.'s framework for combining methods in a single research project through: data triangulation, methodological complementarity, methodological initiation, and methodological expansion. We argue that: (1) flexible and self-reflexive methodological procedures allowed us to seize strategic opportunities to document unexpected and sometimes contradictory findings as they emerged to generate new research questions, (2) iteratively mixing methods increased the scope, reliability, and generalizability of our data, and (3) interdisciplinary collaboration contributed to a scientific "value added" that allowed for more robust theoretical and practical findings about drug use and risk-taking.}, } @article {pmid23311456, year = {2013}, author = {Davis, LC and Rane, S and Hiscock, M}, title = {Serial recall of visuospatial and verbal information with and without material-specific interference: implications for contemporary models of working memory.}, journal = {Memory (Hove, England)}, volume = {21}, number = {7}, pages = {778-797}, doi = {10.1080/09658211.2012.756037}, pmid = {23311456}, issn = {1464-0686}, mesh = {Adolescent ; Attention ; Female ; Humans ; Male ; *Memory, Short-Term ; *Mental Recall ; *Models, Psychological ; Photic Stimulation ; Psychomotor Performance ; *Recognition, Psychology ; *Serial Learning ; *Spatial Behavior ; *Verbal Learning ; Young Adult ; }, abstract = {A longstanding question in working memory (WM) research concerns the fractionation of verbal and nonverbal processing. Although some contemporary models include both domain-specific and general-purpose mechanisms, the necessity to postulate differential processing of verbal and nonverbal material remains unclear. In the present two-experiment series we revisit the order reconstruction paradigm that Jones, Farrand, Stuart, and Morris (1995) used to support a unitary model of WM. Goals were to assess (1) whether serial position curves for dot positions differ from curves for letter names; and (2) whether selective interference can be demonstrated. Although we replicated Jones et al.'s finding of similar serial position curves for the two tasks, this similarity could reflect the demands of the order reconstruction paradigm rather than undifferentiated processing of verbal and nonverbal stimuli. Both generalised and material-specific interference was found, which can be attributed to competition between primary and secondary tasks for attentional resources. As performance levels for the combined primary and secondary tasks exceed active WM capacity limits, primary task items apparently are removed from active memory during processing of the secondary list and held temporarily in maintenance storage. We conclude that active WM is multimodal but maintenance stores may be domain specific.}, } @article {pmid23299259, year = {2012}, author = {King, PR and Donnelly, KT and Donnelly, JP and Dunnam, M and Warner, G and Kittleson, CJ and Bradshaw, CB and Alt, M and Meier, ST}, title = {Psychometric study of the Neurobehavioral Symptom Inventory.}, journal = {Journal of rehabilitation research and development}, volume = {49}, number = {6}, pages = {879-888}, doi = {10.1682/jrrd.2011.03.0051}, pmid = {23299259}, issn = {1938-1352}, mesh = {Adult ; Afghan Campaign 2001- ; Anxiety/psychology ; Brain Injuries/*diagnosis/psychology ; Depression/psychology ; Factor Analysis, Statistical ; Female ; Hospitals, Veterans ; Humans ; Iraq War, 2003-2011 ; Male ; Middle Aged ; New York ; Personality Inventory ; Post-Concussion Syndrome/complications/*diagnosis/psychology ; Psychometrics/*statistics & numerical data ; Reproducibility of Results ; Sensitivity and Specificity ; Socioeconomic Factors ; Stress Disorders, Post-Traumatic/diagnosis/*psychology ; *Surveys and Questionnaires ; Trauma Severity Indices ; United States ; United States Department of Veterans Affairs ; Veterans/*psychology ; Young Adult ; }, abstract = {The Department of Veterans Affairs (VA) uses the Neurobehavioral Symptom Inventory (NSI) to measure postconcussive symptoms in its comprehensive traumatic brain injury (TBI) evaluation. This study examined the NSI's item properties, internal consistency, and external validity. Data were obtained from a federally funded study of the experiences of combat veterans. Participants included 500 Operations Iraqi and Enduring Freedom veterans, 219 of whom sustained at least one TBI. Data were collected at five VA medical centers and one VA outpatient clinic across upstate New York. Measures included neuropsychological interview, NSI, Beck Anxiety Inventory, Beck Depression Inventory-II, and Posttraumatic Stress Disorder Checklist-Military Version. The NSI demonstrated high internal consistency (total alpha = 0.95; subscale alpha = 0.88 to 0.92). Subscale totals based on Caplan et al.'s factor analysis correlated highly with the NSI total score (r = 0.88 to 0.93). NSI scores differentiated veterans with TBI history from those without but were strongly influenced by variance associated with probable posttraumatic stress disorder, depression, and generalized anxiety. Results suggest that the NSI is a reliable and valid measure of postconcussive symptoms. Scale validity is evident in the differentiation of TBI and non-TBI classifications. The scale domain is not limited to TBI, however, and extends to detection of probable effects of additional affective disorders prevalent in the veteran population.}, } @article {pmid23298097, year = {2013}, author = {Lee, CJ and Kupinski, MA and Volokh, L}, title = {Assessment of cardiac single-photon emission computed tomography performance using a scanning linear observer.}, journal = {Medical physics}, volume = {40}, number = {1}, pages = {011906}, pmid = {23298097}, issn = {2473-4209}, support = {RC1 EB010974/EB/NIBIB NIH HHS/United States ; RC1-EB010974/EB/NIBIB NIH HHS/United States ; }, mesh = {Heart/*diagnostic imaging ; Humans ; Image Processing, Computer-Assisted/*methods ; Phantoms, Imaging ; ROC Curve ; Signal-To-Noise Ratio ; Tomography, Emission-Computed, Single-Photon/*methods ; }, abstract = {PURPOSE: Single-photon emission computed tomography (SPECT) is widely used to detect myocardial ischemia and myocardial infarction. It is important to assess and compare different SPECT system designs in order to achieve the highest detectability of cardiac defects.

METHODS: Whitaker et al.'s study ["Estimating random signal parameters from noisy images with nuisance parameters: linear and scanning-linear methods," Opt. Express 16(11), 8150-8173 (2008)] on the scanning linear observer (SLO) shows that the SLO can be used to estimate the location and size of signals. One major advantage of the SLO is that it can be used with projection data rather than with reconstruction data. Thus, this observer model assesses the overall hardware performance independent of any reconstruction algorithm. In addition, the computation time of image quality studies is significantly reduced. In this study, three systems based on the design of the GE cadmium zinc telluride-based dedicated cardiac SPECT camera Discovery 530c were assessed. This design, which is officially named the Alcyone Technology: Discovery NM 530c, was commercialized in August, 2009. The three systems, GE27, GE19, and GE13, contain 27, 19, and 13 detectors, respectively. Clinically, a human heart can be virtually segmented into three coronary artery territories: the left-anterior descending artery, left-circumflex artery, and right coronary artery. One of the most important functions of a cardiac SPECT system is to produce images from which a radiologist can accurately predict in which territory the defect exists [http://www.asnc.org/media/PDFs/PPReporting081511.pdf, Guideline from American Society of Nuclear Cardiology]. A good estimation of the extent of the defect from the projection images is also very helpful for determining the seriousness of the myocardial ischemia. In this study, both the location and extent of defects were estimated by the SLO, and the system performance was assessed by localization receiver operating characteristic (LROC) [P. Khurd and G. Gindi, "Decision strategies maximizing the area under the LROC curve," Proc. SPIE 5749, 150-161 (2005)] or estimation receiver operating characteristic (EROC) [E. Clarkson, "Estimation receiver operating characteristic curve and ideal observers for combined detection/estimation tasks," J. Opt. Soc. Am. A 24, B91-B98 (2007)] curves.

RESULTS: The area under the LROC/EROC curve (AULC/AUEC) and the true positive fraction (TPF) at a specific false positive fraction (FPF) can be treated as the figures of merit. For radii estimation with a 1 mm tolerance, the AUEC values of the GE27, GE19, and GE13 systems are 0.8545, 0.8488, and 0.8329, and the TPF at FPF = 5% are 77.1%, 76.46%, and 73.55%, respectively. The assessment of all three systems revealed that the GE19 system yields estimated information and cardiac defect detectability very close to those of the GE27 system while using eight fewer detectors. Thus, 30% of the expensive detector units can be removed with confidence.

CONCLUSIONS: As the results show, a combination of the SLO and LROC/EROC curves can determine the configuration that yields the most relevant estimation/detection information. Thus, this is a useful method for assessing cardiac SPECT systems.}, } @article {pmid23294407, year = {2013}, author = {Coutu, MF and Durand, MJ and Marchand, A and Labrecque, ME and Berbiche, D and Cadieux, G}, title = {Factors associated with generalized anxiety in workers undergoing work rehabilitation for persistent musculoskeletal pain.}, journal = {Disability and rehabilitation}, volume = {35}, number = {19}, pages = {1599-1607}, doi = {10.3109/09638288.2012.748833}, pmid = {23294407}, issn = {1464-5165}, mesh = {Adult ; Anxiety/*diagnosis/psychology ; Anxiety Disorders/*diagnosis/psychology ; Attitude ; Cognition ; Diagnostic and Statistical Manual of Mental Disorders ; Fear ; Female ; Humans ; Male ; Middle Aged ; Models, Psychological ; Musculoskeletal Pain/psychology/*rehabilitation ; Orientation ; Patient Acceptance of Health Care ; Problem Solving ; Prospective Studies ; Quebec ; Surveys and Questionnaires ; Time Factors ; *Uncertainty ; }, abstract = {PURPOSE: To document in workers having a work disability due to a musculoskeletal disorder (MSD), the presence and variation over time of their intolerance of uncertainty and its maintenance factors as defined in Dugas et al.'s generalized anxiety disorder (GAD) model, i.e. worries, negative problem orientation, beliefs about the usefulness of worrying, cognitive avoidance and their consequences on depressive symptoms.

METHODS: An observational, prospective repeated-measures design was retained. Thirty-nine workers with an MSD having caused a work absence of over three months and who were beginning a work rehabilitation program were recruited and evaluated at four moments (beginning of rehabilitation program, first hours of work exposure, 50% of regular working hours and end of rehabilitation program). Validated self-report questionnaires measuring intolerance of uncertainty and its maintenance factors were administered. Finally, the Worry and Anxiety Questionnaire measured the presence and intensity of GAD symptoms as defined in the DSM-IV-TR.

RESULTS: Fifty percent of the workers initially exhibited GAD symptoms. Concerning the variation over time, improvements were noted in all GAD-related factors during the program, particularly with the first hours of work exposure. At the end of rehabilitation, only 21% of the participants still met GAD diagnostic criteria.

CONCLUSION: Workers with an MSD causing a work disability averaging one year in length and enrolled in a work rehabilitation program exhibited a high level of anxiety at the beginning of the work rehabilitation program. Workers perceived a usefulness in worrying and presented some intolerance of uncertainty and some cognitive avoidance strategies. According to Dugas et al.'s GAD model, the intensity of the symptoms associated with GAD development and maintenance factors was, however, not typical of a GAD. IMPLICATION FOR REHABILITATION: A reconceptualization of the problem in terms of reducing the work disability rather than reducing pain may constitute a promising avenue to reduce anxiety symptoms. Future studies should look at the specific impact of work exposure, not only on pain symptoms but also on worries. The high level of anxiety and the reported worries by workers stresses the importance of studying the hypothesis of a workplace phobia in order to improve clinical practice guidelines.}, } @article {pmid23294094, year = {2013}, author = {Lindquist, KA and Siegel, EH and Quigley, KS and Barrett, LF}, title = {The hundred-year emotion war: are emotions natural kinds or psychological constructions? Comment on Lench, Flores, and Bench (2011).}, journal = {Psychological bulletin}, volume = {139}, number = {1}, pages = {255-263}, pmid = {23294094}, issn = {1939-1455}, support = {DP1 OD003312/OD/NIH HHS/United States ; DP1OD003312/OD/NIH HHS/United States ; }, mesh = {Behavior/*physiology ; Cognition/*physiology ; Emotions/*physiology ; Humans ; Judgment/*physiology ; }, abstract = {For the last century, there has been a continuing debate about the nature of emotion. In the most recent offering in this scientific dialogue, Lench, Flores, and Bench (2011) reported a meta-analysis of emotion induction research and claimed support for the natural kind hypothesis that discrete emotions (e.g., happiness, sadness, anger, and anxiety) elicit specific changes in cognition, judgment, behavior, experience, and physiology. In this article, we point out that Lench et al. (2011) is not the final word on the emotion debate. First, we point out that Lench et al.'s findings do not support their claim that discrete emotions organize cognition, judgment, experience, and physiology because they did not demonstrate emotion-consistent and emotion-specific directional changes in these measurement domains. Second, we point out that Lench et al.'s findings are in fact consistent with the alternative (a psychological constructionist approach to emotion). We close by appealing for a construct validity approach to emotion research, which we hope will lead to greater consensus on the operationalization of the natural kind and psychological construction approaches, as well as the criteria required to finally resolve the emotion debate.}, } @article {pmid23294092, year = {2013}, author = {Rouder, JN and Morey, RD and Province, JM}, title = {A Bayes factor meta-analysis of recent extrasensory perception experiments: comment on Storm, Tressoldi, and Di Risio (2010).}, journal = {Psychological bulletin}, volume = {139}, number = {1}, pages = {241-247}, doi = {10.1037/a0029008}, pmid = {23294092}, issn = {1939-1455}, mesh = {*Acoustic Stimulation ; Humans ; *Models, Psychological ; Parapsychology/*methods ; }, abstract = {Psi phenomena, such as mental telepathy, precognition, and clairvoyance, have garnered much recent attention. We reassess the evidence for psi effects from Storm, Tressoldi, and Di Risio's (2010) meta-analysis. Our analysis differs from Storm et al.'s in that we rely on Bayes factors, a Bayesian approach for stating the evidence from data for competing theoretical positions. In contrast to more conventional analyses, inference by Bayes factors allows the analyst to state evidence for the no-psi-effect null as well as for a psi-effect alternative. We find that the evidence from Storm et al.'s presented data set favors the existence of psi by a factor of about 6 billion to 1, which is noteworthy even for a skeptical reader. Much of this effect, however, may reflect difficulties in randomization: Studies with computerized randomization have smaller psi effects than those with manual randomization. When the manually randomized studies are excluded and omitted studies included, the Bayes factor evidence is at most 330 to 1, a greatly attenuated value. We argue that this value is unpersuasive in the context of psi because there is no plausible mechanism and because there are almost certainly omitted replication failures.}, } @article {pmid23294089, year = {2013}, author = {Walker, CM and Gopnik, A}, title = {Pretense and possibility--a theoretical proposal about the effects of pretend play on development: comment on Lillard et al. (2013).}, journal = {Psychological bulletin}, volume = {139}, number = {1}, pages = {40-44}, doi = {10.1037/a0030151}, pmid = {23294089}, issn = {1939-1455}, mesh = {Child Development/*physiology ; Female ; Humans ; Male ; Play and Playthings/*psychology ; }, abstract = {The review by Lillard et al. (2013) highlighted the need for additional research to better clarify the nature of the relationship between pretend play and development. However, the authors did not provide a proposal for how to structure the direction of this future work. Here, we provide a possible framework for generating additional research. This theoretical proposal is based on recent computational approaches to cognition, in which counterfactual reasoning plays a central role in causal learning. We propose that pretend play initially emerges as a product of the cognitive mechanisms underlying human learning and then feeds back to become critical for enhancing the optimal functioning of these same processes. More specifically, we argue that pretending is in fact 1 of several forms of counterfactual reasoning, which is essential to causal cognition-and that the act of engaging in pretend scenarios may provide early opportunities to practice the skills that were initially responsible for its appearance. Here, we provide a brief overview of this theoretical framework, consider how these ideas may be integrated with the previous work covered in Lillard et al.'s (2013) review, and suggest some empirically testable questions to direct future directions.}, } @article {pmid23286107, year = {2012}, author = {Bilgic, B and Setsompop, K and Cohen-Adad, J and Wedeen, V and Wald, LL and Adalsteinsson, E}, title = {Accelerated diffusion spectrum imaging with compressed sensing using adaptive dictionaries.}, journal = {Medical image computing and computer-assisted intervention : MICCAI ... International Conference on Medical Image Computing and Computer-Assisted Intervention}, volume = {15}, number = {Pt 3}, pages = {1-9}, pmid = {23286107}, support = {P41 RR014075/RR/NCRR NIH HHS/United States ; R01 EB006847/EB/NIBIB NIH HHS/United States ; R01 EB007942/EB/NIBIB NIH HHS/United States ; }, mesh = {Algorithms ; Brain/*anatomy & histology ; Connectome/*methods ; Data Compression/*methods ; Diffusion Tensor Imaging/*methods ; Image Enhancement/methods ; Image Interpretation, Computer-Assisted/*methods ; Imaging, Three-Dimensional/*methods ; Nerve Fibers, Myelinated/*ultrastructure ; Reproducibility of Results ; Sensitivity and Specificity ; }, abstract = {Diffusion spectrum imaging (DSI) offers detailed information on complex distributions of intravoxel fiber orientations at the expense of extremely long imaging times (1 hour). It is possible to accelerate DSI by sub-Nyquist sampling of the q-space followed by nonlinear reconstruction to estimate the diffusion probability density functions (pdfs). Recent work by Menzel et al. imposed sparsity constraints on the pdfs under wavelet and total variation (TV) transforms. As the performance of Compressed Sensing (CS) reconstruction depends strongly on the level of sparsity in the selected transform space, a dictionary specifically tailored for sparse representation of diffusion pdfs can yield higher fidelity results. To our knowledge, this work is the first application of adaptive dictionaries in DSI, whereby we reduce the scan time of whole brain DSI acquisition from 50 to 17 min while retaining high image quality. In vivo experiments were conducted with the novel 3T Connectome MRI, whose strong gradients are particularly suited for DSI. The RMSE from the proposed reconstruction is up to 2 times lower than that of Menzel et al.'s method, and is actually comparable to that of the fully-sampled 50 minute scan. Further, we demonstrate that a dictionary trained using pdfs from a single slice of a particular subject generalizes well to other slices from the same subject, as well as to slices from another subject.}, } @article {pmid23279880, year = {2013}, author = {Chaudhary, MZ and Ahmad, N and Mashiatullah, A and Ahmad, N and Ghaffar, A}, title = {Geochemical assessment of metal concentrations in sediment core of Korangi Creek along Karachi Coast, Pakistan.}, journal = {Environmental monitoring and assessment}, volume = {185}, number = {8}, pages = {6677-6691}, pmid = {23279880}, issn = {1573-2959}, mesh = {*Environmental Monitoring ; Geologic Sediments/*chemistry ; Metals/*analysis ; Pakistan ; Water Pollutants, Chemical/*analysis ; Water Pollution, Chemical/statistics & numerical data ; }, abstract = {Sediment core from Korangi Creek, one of the polluted coastal locations along the Karachi Coast Pakistan, was collected to trace the history of marine pollution and to determine the impact of industrial activity in the area. Down core variation of metals such as Ca, K, Mg, Al, S, Ti, V, Cr, Mn, Fe, Ni, Cu and Zn was studied in the 72.0 cm core. Nuclear analytical techniques, proton induced X-rays emission (PIXE), was employed to ascertain the chemical composition in sediment core. Grain size analysis and sediment composition of cored samples indicated that Korangi creek sediments are clayey in nature. Correlation matrix revealed a strong association of Ni, Cu, Cr and Zn with Fe and Mn. To infer anthropogenic input, enrichment factor (EF), degree of contamination and pollution load index were calculated. EF showed severe enrichment in surface sediment for Ni, Cu, Cr and Zn, indicating increased industrial effluents discharge in recent years. The study suggests that heavy metal discharge in the area should be regulated. If the present trend of enrichment is allowed to continue unabated, it is most likely that the local food web complexes in the creek might be at highest risk.}, } @article {pmid25277593, year = {2013}, author = {Latinne, A and Chaval, Y and Waengsothorn, S and Rojanadilok, P and Eiamampai, K and Sribuarod, K and Herbreteau, V and Morand, S and Michaux, JR}, title = {Is Leopoldamys neilli (Rodentia, Muridae) a synonym of Leopoldamys herberti? A reply to Balakirev et al. (2013).}, journal = {Zootaxa}, volume = {3731}, number = {}, pages = {589-598}, doi = {10.11646/zootaxa.3731.4.10}, pmid = {25277593}, issn = {1175-5326}, mesh = {Animals ; Asia, Southeastern ; Cytochromes b/genetics ; Demography ; Electron Transport Complex IV/genetics ; Gene Expression Regulation ; Molecular Sequence Data ; Muridae/*anatomy & histology/*classification/genetics/physiology ; Phylogeny ; Species Specificity ; }, abstract = {Recently, Balakirev et al. (2013) presented a taxonomic revision of the genus Leopoldamys based on phylogenetic analyses. They identified five main Leopoldamys genetic lineages and suggested to rename several of them. According to these authors, the genetic lineage previously thought to belong to L. edwardsi (lineage L1) should be assigned to L. revertens while L. neilli (lineage L2) should be considered as a junior synonym of L. herberti. Using molecular and morphological data from a large sampling of Leopoldamys specimens, the aim of the present study was to investigate the taxonomic status of L. herberti and L. neilli. This study reveals that, contrary to Balakirev et al.'s statement, both genetic lineages L1 and L2 occur in Nakhon Ratchasima Province, close to the type locality of L. herberti. We also show that the external measurements and color pattern of L. herberti are highly similar to those of L1 specimens but are not consistent with the morphology of L2 specimens. Therefore these results strongly suggest that L. herberti should be assigned to the genetic lineage L1. Consequently L. neilli should not be considered as a junior synonym of L. herberti and this study confirms that the appropriate name of the genetic lineage L2 is L. neilli. Moreover, as our results show that L. herberti should be assigned to the lineage L1, this name has nomenclatural priority over L. revertens, the species name suggested by Balakirev et al. (2013) for this lineage.}, } @article {pmid23268730, year = {2013}, author = {Burdick, DJ}, title = {Response to Deng et al.'s LRRK2 patent review.}, journal = {Expert opinion on therapeutic patents}, volume = {23}, number = {2}, pages = {279}, doi = {10.1517/13543776.2013.757594}, pmid = {23268730}, issn = {1744-7674}, mesh = {Animals ; Antiparkinson Agents/*pharmacology ; *Drug Design ; Humans ; *Patents as Topic ; Protein Kinase Inhibitors/*pharmacology ; Protein Serine-Threonine Kinases/*antagonists & inhibitors ; }, } @article {pmid23267027, year = {2016}, author = {Combescure, C and Courvoisier, DS and Haller, G and Perneger, TV}, title = {Meta-analysis of two-arm studies: Modeling the intervention effect from survival probabilities.}, journal = {Statistical methods in medical research}, volume = {25}, number = {2}, pages = {857-871}, doi = {10.1177/0962280212469716}, pmid = {23267027}, issn = {1477-0334}, mesh = {Breast Neoplasms/diagnosis/mortality ; Disease-Free Survival ; Early Detection of Cancer ; Female ; Humans ; Leukemia, Myeloid, Acute/drug therapy/surgery ; Neoplasm Recurrence, Local/diagnosis/mortality ; *Proportional Hazards Models ; Time Factors ; }, abstract = {Pooling the hazard ratios is not always feasible in meta-analyses of two-arm survival studies, because the measure of the intervention effect is not systematically reported. An alternative approach proposed by Moodie et al. is to use the survival probabilities of the included studies, all collected at a single point in time: the intervention effect is then summarised as the pooled ratio of the logarithm of survival probabilities (which is an estimator of the hazard ratios when hazards are proportional). In this article, we propose a generalization of this method. By using survival probabilities at several points in time, this generalization allows a flexible modeling of the intervention over time. The method is applicable to partially proportional hazards models, with the advantage of not requiring the specification of the baseline survival. As in Moodie et al.'s method, the study-level factors modifying the survival functions can be ignored as long as they do not modify the intervention effect. The procedures of estimation are presented for fixed and random effects models. Two illustrative examples are presented.}, } @article {pmid23242132, year = {2012}, author = {Rabotyagov, S and Campbell, T and Valcu, A and Gassman, P and Jha, M and Schilling, K and Wolter, C and Kling, C}, title = {Spatial multiobjective optimization of agricultural conservation practices using a SWAT model and an evolutionary algorithm.}, journal = {Journal of visualized experiments : JoVE}, volume = {}, number = {70}, pages = {e4009}, pmid = {23242132}, issn = {1940-087X}, mesh = {Agriculture/*methods ; *Algorithms ; Conservation of Natural Resources/*methods ; Cost-Benefit Analysis ; Hydrology/*methods ; *Models, Theoretical ; Water Movements ; *Water Resources ; }, abstract = {Finding the cost-efficient (i.e., lowest-cost) ways of targeting conservation practice investments for the achievement of specific water quality goals across the landscape is of primary importance in watershed management. Traditional economics methods of finding the lowest-cost solution in the watershed context (e.g.,(5,12,20)) assume that off-site impacts can be accurately described as a proportion of on-site pollution generated. Such approaches are unlikely to be representative of the actual pollution process in a watershed, where the impacts of polluting sources are often determined by complex biophysical processes. The use of modern physically-based, spatially distributed hydrologic simulation models allows for a greater degree of realism in terms of process representation but requires a development of a simulation-optimization framework where the model becomes an integral part of optimization. Evolutionary algorithms appear to be a particularly useful optimization tool, able to deal with the combinatorial nature of a watershed simulation-optimization problem and allowing the use of the full water quality model. Evolutionary algorithms treat a particular spatial allocation of conservation practices in a watershed as a candidate solution and utilize sets (populations) of candidate solutions iteratively applying stochastic operators of selection, recombination, and mutation to find improvements with respect to the optimization objectives. The optimization objectives in this case are to minimize nonpoint-source pollution in the watershed, simultaneously minimizing the cost of conservation practices. A recent and expanding set of research is attempting to use similar methods and integrates water quality models with broadly defined evolutionary optimization methods(3,4,9,10,13-15,17-19,22,23,25). In this application, we demonstrate a program which follows Rabotyagov et al.'s approach and integrates a modern and commonly used SWAT water quality model(7) with a multiobjective evolutionary algorithm SPEA2(26), and user-specified set of conservation practices and their costs to search for the complete tradeoff frontiers between costs of conservation practices and user-specified water quality objectives. The frontiers quantify the tradeoffs faced by the watershed managers by presenting the full range of costs associated with various water quality improvement goals. The program allows for a selection of watershed configurations achieving specified water quality improvement goals and a production of maps of optimized placement of conservation practices.}, } @article {pmid23240595, year = {2013}, author = {Anderson, KK}, title = {Health service registry data in psychiatric epidemiology: challenges for definition and interpretation: an editorial comment to: Okkels et al.'s 'changes in the diagnosed incidence of early onset schizophrenia over four decades' (1).}, journal = {Acta psychiatrica Scandinavica}, volume = {127}, number = {1}, pages = {9-10}, doi = {10.1111/j.1600-0447.2012.01916.x}, pmid = {23240595}, issn = {1600-0447}, mesh = {Female ; Humans ; Male ; Registries/*statistics & numerical data ; Schizophrenia/*epidemiology ; }, } @article {pmid23238909, year = {2013}, author = {Atkins, MS and Lakind, D}, title = {Usual care for clinicians, unusual care for their clients: rearranging priorities for children's mental health services.}, journal = {Administration and policy in mental health}, volume = {40}, number = {1}, pages = {48-51}, pmid = {23238909}, issn = {1573-3289}, support = {P20 MH078458/MH/NIMH NIH HHS/United States ; }, mesh = {Adolescent Health Services/*standards ; Child Health Services/*standards ; Community Mental Health Services/*standards ; Humans ; *Quality Improvement ; }, abstract = {Garland et al.’s comprehensive review of the state of clinic-based community-based mental health care for U.S. children highlights many recent advances in usual care (UC) while also describing the continued gap between need and service provision, the limited effectiveness of services provided, and a number of other obstructions and dilemmas ranging from perceived stigma on the part of families to limited fiscal resources on the part of service providers. Based on these long-standing concerns, the review summarizes research on three foci for change and offers future directions for each: Enhanced engagement strategies to retain families in services, improved training and support to increase the use of evidenced based practices, and expanded measurement and feedback systems to monitor services in real time. Unaddressed, however, is whether these changes are sufficient to reform children’s mental health care. Even if enacted extensively and outstandingly – a feat we imagine that nobody familiar with UC would realistically expect – will unmet need for care improve and effective services be available to the large number of children in need of mental health services?}, } @article {pmid23868168, year = {2012}, author = {Koch, JM and Holder, MT}, title = {An Algorithm for Calculating the Probability of Classes of Data Patterns on a Genealogy.}, journal = {PLoS currents}, volume = {4}, number = {}, pages = {e4fd1286980c08}, pmid = {23868168}, issn = {2157-3999}, support = {R25 GM062232/GM/NIGMS NIH HHS/United States ; }, abstract = {Felsenstein's pruning algorithm allows one to calculate the probability of any particular data pattern arising on a phylogeny given a model of character evolution. Here we present a similar dynamic programming algorithm. Our algorithm treats the tree and model as known. The algorithm makes it feasible to calculate the probability that a randomly selected character will be a member of a particular class of character patterns. Specifically, we are interested in binning patterns by the number of parsimony steps and the set of states observed at the tips of the tree. This algorithm was developed to expand the range of data set sizes that can be used with Waddell et al.'s marginal testing approach for assessing the adequacy of a model. The algorithms introduced can also be used in likelihood calculations which correct for ascertainment biases. For example, Lewis introduced an Mkv model which corrects for the lack of constant sites. The probability of a constant pattern arising can be calculated using the algorithm that we present, or by enumerating all possible constant patterns and calculating the probability of each one. Because the number of constant data patterns is small, both methods are efficient. However, elaborations of the Mkv model (such as those in Nylander et al) require calculating the probability of parsimony-uninformative patterns arising. For large trees and characters with many possible character states, the number of possible parismony-uninformative patterns is immense. In these cases, the algorithms introduced here will be more efficient. The algorithm has been implemented in open source software written in C++.}, } @article {pmid23228949, year = {2013}, author = {Urbani, B and Youlatos, D}, title = {Positional behavior and substrate use of Micromys minutus (Rodentia: Muridae): insights for understanding primate origins.}, journal = {Journal of human evolution}, volume = {64}, number = {2}, pages = {130-136}, doi = {10.1016/j.jhevol.2012.10.006}, pmid = {23228949}, issn = {1095-8606}, mesh = {Animals ; *Behavior, Animal ; *Biological Evolution ; Female ; *Locomotion ; Male ; Murinae/physiology/*psychology ; Postural Balance ; }, abstract = {Several hypotheses have been proposed to explain the origins of primates, suggesting evolutionary scenarios that are usually paralleled to modern mammalian models that partly simulate the morpho-behavioral apomorphies of primates. The current study examines substrate use and positional behavior of tiny-sized Eurasian harvest mice (Micromys minutus) as living models for inferring the evolution of versatile behavior, flexible branch use and pedal grasping in early small-sized primates. Micromys exhibits a diverse locomotor repertoire composed of clambering and climbing, and uses postural modes requiring secure pedal grasping. It also makes considerable use of fine flexible substrates of various inclinations during both feeding/foraging and traveling. This profile seems to represent an intermediate step between stage 2 (Tupaia-stage) and stage 3 (Caluromys-stage) in Sargis et al.'s (2007) primate evolutionary scenario. Furthermore, our findings suggest that tiny size in itself brings a unique level of flexibility in posture and locomotion that has heretofore been underappreciated in the primate evolution literature.}, } @article {pmid23227491, year = {2012}, author = {Destro Bisol, G and Capocasa, M and Anagnostou, P}, title = {When gender matters: new insights into the relationships between social systems and the genetic structure of human populations.}, journal = {Molecular ecology}, volume = {21}, number = {20}, pages = {4917-4920}, doi = {10.1111/mec.12001}, pmid = {23227491}, issn = {1365-294X}, mesh = {Female ; *Genetic Variation ; *Genetics, Population ; *Human Migration ; Humans ; Male ; }, abstract = {Due to its important effects on the ecological dynamics and the genetic structure of species, biologists have long been interested in gender-biased dispersal, a condition where one gender is more prone to move from the natal site. More recently, this topic has attracted a great attention from human evolutionary geneticists. Considering the close relations between residential rules and social structure, gender-biased dispersal is, in fact, regarded as an important case study concerning the effects of socio-cultural factors on human genetic variation. It all started with the seminal paper by Mark Seielstad, Erich Minch and Luigi Luca Cavalli Sforza from Stanford University (Seielstad et al. 1998). They observed a larger differentiation for Y-chromosome than mitochondrial DNA between extant human populations, purportedly a consequence of the prevalence of long-term patrilocality in human societies. Subsequent studies, however, have highlighted the need to consider geographically close and culturally homogeneous groups, disentangle signals due to different peopling events and obtain unbiased estimates of genetic diversity. In this issue of Molecular Ecology, not only do Marks et al. (2012) adopt an experimental design which addresses these concerns, but they also take a further and important step forward by integrating the genetic analysis of two distant populations, the Basotho and Spanish, with data regarding migration rates and matrimonial distances. Using both empirical evidence and simulations, the authors show that female-biased migration due to patrilocality might shape the genetic structure of human populations only at short ranges and under substantial differences in migration rates between genders. Providing a quantitative framework for future studies of the effects of residential rules on the human genome, this study paves the way for further developments in the field. On a wider perspective, Marks et al.'s work demonstrates the power of approaches which integrate biological, cultural and demographic lines of evidence in the study of relations between social and genetic structures of human populations.}, } @article {pmid23219572, year = {2013}, author = {Constant, I and Rigouzzo, A and Louvet, N}, title = {[Update on propofol TCI in children].}, journal = {Annales francaises d'anesthesie et de reanimation}, volume = {32}, number = {1}, pages = {e37-42}, doi = {10.1016/j.annfar.2012.10.023}, pmid = {23219572}, issn = {1769-6623}, mesh = {Anesthesia, Intravenous/*methods/trends ; *Anesthetics, Intravenous/pharmacokinetics ; Child ; Child, Preschool ; Humans ; Pediatrics/*methods/trends ; *Propofol/pharmacokinetics ; }, abstract = {For several years, total intravenous anaesthesia (TIVA) has demonstrated many advantages that allow considering propofol anaesthesia as an interesting alternative in pediatric anaesthesia. TCI in children requires calculation and validation of pharmacokinetic (PK) models specifically adapted to the paediatric population. Several PK models based on a 3-compartement approach have been proposed in children: all these models, which integrate only weight as covariable, show increased distribution volumes with a wide interindividual variability. The particular importance to include physiological covariables, as age and lean body mass, to describe metabolic processes during growth and maturation in pediatric PKPD models is in agreement with recent allometric scaling works in children. However, as pharmacodynamic (PD) parameters are still debated in children, there is up to now, no PKPD model currently available for paediatric anaesthesia. Schnider et al.'s model, a model described in adults that includes numerous covariables, may be adapted and more efficient than the classical paediatric models to describe propofol-PKPD relationship in children over 5years. Whatever the model, a pharmacodynamic feedback such as the bispectral index may be useful to counteract interindividual variability in the paediatric population.}, } @article {pmid23211645, year = {2013}, author = {Uhlmann, EL}, title = {The logic of moral outrage.}, journal = {The Behavioral and brain sciences}, volume = {36}, number = {1}, pages = {38}, doi = {10.1017/S0140525X12000465}, pmid = {23211645}, issn = {1469-1825}, mesh = {*Choice Behavior ; Female ; Humans ; Male ; *Marriage ; *Morals ; *Sexual Partners ; }, abstract = {McCullough et al.’s functionalist model of revenge is highly compatible with the person-centered approach to moral judgment, which emphasizes the adaptive manner in which social perceivers derive character information from moral acts. Evidence includes act–person dissociations in which an act is seen as less immoral than a comparison act, yet as a clearer indicator of poor moral character.}, } @article {pmid23211378, year = {2013}, author = {Gintis, H}, title = {An implausible model and evolutionary explanation of the revenge motive.}, journal = {The Behavioral and brain sciences}, volume = {36}, number = {1}, pages = {21-22}, doi = {10.1017/S0140525X12000386}, pmid = {23211378}, issn = {1469-1825}, mesh = {*Adaptation, Psychological ; Aggression/*psychology ; *Cognition ; *Forgiveness ; Humans ; *Motivation ; }, abstract = {McCullough et al.’s target article is a psychological version of the reputation models pioneered by biologist Robert Trivers (1971) and economist Robert Frank (1988). The authors, like Trivers and Frank, offer an implausible explanation of the fact that revenge is common even when there are no possible reputational effects. I sketch a more plausible model based on recent research.}, } @article {pmid23211274, year = {2013}, author = {Beckerman, S}, title = {The cultural shaping of revenge.}, journal = {The Behavioral and brain sciences}, volume = {36}, number = {1}, pages = {18-19}, doi = {10.1017/S0140525X12000350}, pmid = {23211274}, issn = {1469-1825}, mesh = {*Choice Behavior ; Female ; Humans ; Male ; *Marriage ; *Morals ; *Sexual Partners ; }, abstract = {There are interesting parallelisms between McCullough et al.’s article and studies of revenge presented by French legal anthropologist Raymond Verdier, particularly as regards the discussion of the increasing likelihood of revenge with increasing social distance. Additionally, the observation that many peoples speak of revenge in the language of debt and repayment, links it with exchanges of benefits as well as costs.}, } @article {pmid23186425, year = {2012}, author = {Dombrowski, K}, title = {Is better drug policy a matter of knowing whose pants are on fire? Kirk Dombrowski on Friedman et al.'s "Has United States drug policy failed? And how could we know?".}, journal = {Substance use & misuse}, volume = {47}, number = {13-14}, pages = {1412-1413}, doi = {10.3109/10826084.2012.723505}, pmid = {23186425}, issn = {1532-2491}, support = {RC1 DA028476/DA/NIDA NIH HHS/United States ; }, mesh = {*Health Policy ; Humans ; Illicit Drugs/*legislation & jurisprudence ; }, } @article {pmid23186424, year = {2012}, author = {Curtis, R}, title = {Richard Curtis on Friedman et al.'s "Has United States drug policy failed? And how could we know?".}, journal = {Substance use & misuse}, volume = {47}, number = {13-14}, pages = {1410-1411}, doi = {10.3109/10826084.2012.723495}, pmid = {23186424}, issn = {1532-2491}, mesh = {*Health Policy ; Humans ; Illicit Drugs/*legislation & jurisprudence ; }, } @article {pmid23186423, year = {2012}, author = {Fordham, A}, title = {Ann Fordham on Friedman et al.'s "Has United States' drug policy failed? And how could we know?".}, journal = {Substance use & misuse}, volume = {47}, number = {13-14}, pages = {1408-1409}, doi = {10.3109/10826084.2012.723530}, pmid = {23186423}, issn = {1532-2491}, mesh = {*Health Policy ; Humans ; Illicit Drugs/*legislation & jurisprudence ; }, } @article {pmid23186422, year = {2012}, author = {Ritter, A}, title = {Alison Ritter on Friedman et al.'s "Has United States drug policy failed? And how could we know?" Policy as structured interaction, engaging multiple voices.}, journal = {Substance use & misuse}, volume = {47}, number = {13-14}, pages = {1406-1407}, doi = {10.3109/10826084.2012.723555}, pmid = {23186422}, issn = {1532-2491}, mesh = {*Health Policy ; Humans ; Illicit Drugs/*legislation & jurisprudence ; }, } @article {pmid23185099, year = {2013}, author = {Mullen, SP and Gothe, NP and McAuley, E}, title = {Evaluation of the Factor Structure of the Rosenberg Self-Esteem Scale in Older Adults.}, journal = {Personality and individual differences}, volume = {54}, number = {2}, pages = {153-157}, pmid = {23185099}, issn = {0191-8869}, support = {R01 AG020118/AG/NIA NIH HHS/United States ; R37 AG025667/AG/NIA NIH HHS/United States ; }, abstract = {The Rosenberg Self-Esteem Scale is the most utilized measure of global self-esteem. Although psychometric studies have generally supported the uni-dimensionality of this 10-item scale, more recently, a stable, response-bias has been associated with the wording of the items (Marsh, Scalas, & Nagengast, 2010). The purpose of this report was to replicate Marsh et al.'s findings in a sample of older adults and to test for invariance across time, gender and levels of education. Our results indicated that indeed a response-bias does exist in esteem responses. Researchers should investigate ways to meaningfully examine and practically overcome the methodological challenges associated with the RSE scale.}, } @article {pmid23180417, year = {2013}, author = {Perruchet, P and Poulin-Charronnat, B}, title = {Challenging prior evidence for a shared syntactic processor for language and music.}, journal = {Psychonomic bulletin & review}, volume = {20}, number = {2}, pages = {310-317}, pmid = {23180417}, issn = {1531-5320}, mesh = {Acoustic Stimulation ; Attention/*physiology ; Cognition/*physiology ; Comprehension/physiology ; *Language ; *Music ; Photic Stimulation ; Reaction Time ; Reading ; Semantics ; }, abstract = {A theoretical landmark in the growing literature comparing language and music is the shared syntactic integration resource hypothesis (SSIRH; e.g., Patel, 2008), which posits that the successful processing of linguistic and musical materials relies, at least partially, on the mastery of a common syntactic processor. Supporting the SSIRH, Slevc, Rosenberg, and Patel (Psychonomic Bulletin & Review 16(2):374-381, 2009) recently reported data showing enhanced syntactic garden path effects when the sentences were paired with syntactically unexpected chords, whereas the musical manipulation had no reliable effect on the processing of semantic violations. The present experiment replicated Slevc et al.'s (2009) procedure, except that syntactic garden paths were replaced with semantic garden paths. We observed the very same interactive pattern of results. These findings suggest that the element underpinning interactions is the garden path configuration, rather than the implication of an alleged syntactic module. We suggest that a different amount of attentional resources is recruited to process each type of linguistic manipulations, hence modulating the resources left available for the processing of music and, consequently, the effects of musical violations.}, } @article {pmid23164427, year = {2012}, author = {Haslam, SA and Reynolds, KJ}, title = {All about us, but never about us: the three-pronged potency of prejudice.}, journal = {The Behavioral and brain sciences}, volume = {35}, number = {6}, pages = {435-436}, doi = {10.1017/S0140525X12001215}, pmid = {23164427}, issn = {1469-1825}, mesh = {*Group Processes ; Humans ; *Interpersonal Relations ; *Prejudice ; *Social Identification ; }, abstract = {Three points that are implicit in Dixon et al.'s paradigm-challenging paper serve to make prejudice potent. First, prejudice reflects understandings of social identity – the relationship of “us” to "them" - that are shared within particular groups. Second, these understandings are actively promoted by leaders who represent and advance in-group identity. Third, prejudice is identified in out-groups, not in-groups.}, } @article {pmid23164339, year = {2012}, author = {Drury, J}, title = {Prejudice is about politics: a collective action perspective.}, journal = {The Behavioral and brain sciences}, volume = {35}, number = {6}, pages = {430-431}, doi = {10.1017/S0140525X12001173}, pmid = {23164339}, issn = {1469-1825}, mesh = {*Group Processes ; Humans ; *Interpersonal Relations ; *Prejudice ; *Social Identification ; }, abstract = {In line with Dixon et al.'s argument, I contend that prejudice should be understood in broadly political rather than in narrowly psychological terms. First, what counts as prejudice is a political judgement. Second, studies of collective action demonstrate that it is in "political" struggles, where subordinate groups together oppose dominant groups, that prejudice can be overcome.}, } @article {pmid23164057, year = {2012}, author = {Maoz, I}, title = {The dangers of prejudice reduction interventions: empirical evidence from encounters between Jews and Arabs in Israel.}, journal = {The Behavioral and brain sciences}, volume = {35}, number = {6}, pages = {441-442}, doi = {10.1017/S0140525X12001276}, pmid = {23164057}, issn = {1469-1825}, mesh = {*Group Processes ; Humans ; *Interpersonal Relations ; *Prejudice ; *Social Identification ; }, abstract = {This commentary focuses on Dixon et al.'s discussion on the dangers of employing prejudice-reduction interventions that seek to promote intergroup harmony in historically unequal societies. Specifically, it illustrates these dangers by discussing my work in Israel (now mentioned in Dixon et al.'s note 6) on the processes and practices through which reconciliation-aimed encounters between Jews and Arabs mitigate sociopolitical change.}, } @article {pmid23161455, year = {2013}, author = {Rosenfeld, MJ}, title = {Nontraditional families and childhood progress through school.}, journal = {Demography}, volume = {50}, number = {3}, pages = {963-969}, pmid = {23161455}, issn = {0070-3370}, mesh = {*Family Characteristics ; *Homosexuality ; Humans ; }, abstract = {Allen et al.'s results depend on their inclusion of children whose family at the time of their grade retention is unknown, plus adopted and foster children whose selection process into families is unknown. Children whose family has been through upheavals or transitions are less likely to make good progress in school than children from stable families. Children raised by stable same-sex couples do remarkably well in school.}, } @article {pmid23159170, year = {2013}, author = {O'Sullivan, M and Raftery, T and Nic Suibhne, T}, title = {Reply to Dr. Yamamoto et al.'s letter.}, journal = {Journal of Crohn's & colitis}, volume = {7}, number = {5}, pages = {e193}, doi = {10.1016/j.crohns.2012.10.014}, pmid = {23159170}, issn = {1876-4479}, mesh = {Crohn Disease/*epidemiology ; Humans ; Obesity/*epidemiology ; Overweight/*epidemiology ; }, } @article {pmid23158572, year = {2013}, author = {Thompson, VA and Turner, JA and Pennycook, G and Ball, LJ and Brack, H and Ophir, Y and Ackerman, R}, title = {The role of answer fluency and perceptual fluency as metacognitive cues for initiating analytic thinking.}, journal = {Cognition}, volume = {128}, number = {2}, pages = {237-251}, doi = {10.1016/j.cognition.2012.09.012}, pmid = {23158572}, issn = {1873-7838}, mesh = {Adult ; Cognition/*physiology ; Facial Expression ; Female ; Humans ; Judgment/physiology ; Male ; Psychomotor Performance/*physiology ; Thinking/*physiology ; Young Adult ; }, abstract = {Although widely studied in other domains, relatively little is known about the metacognitive processes that monitor and control behaviour during reasoning and decision-making. In this paper, we examined the conditions under which two fluency cues are used to monitor initial reasoning: answer fluency, or the speed with which the initial, intuitive answer is produced (Thompson, Prowse Turner, & Pennycook, 2011), and perceptual fluency, or the ease with which problems can be read (Alter, Oppenheimer, Epley, & Eyre, 2007). The first two experiments demonstrated that answer fluency reliably predicted Feeling of Rightness (FOR) judgments to conditional inferences and base rate problems, which subsequently predicted the amount of deliberate processing as measured by thinking time and answer changes; answer fluency also predicted retrospective confidence judgments (Experiment 3b). Moreover, the effect of answer fluency on reasoning was independent from the effect of perceptual fluency, establishing that these are empirically independent constructs. In five experiments with a variety of reasoning problems similar to those of Alter et al. (2007), we found no effect of perceptual fluency on FOR, retrospective confidence or accuracy; however, we did observe that participants spent more time thinking about hard to read stimuli, although this additional time did not result in answer changes. In our final two experiments, we found that perceptual disfluency increased accuracy on the CRT (Frederick, 2005), but only amongst participants of high cognitive ability. As Alter et al.'s samples were gathered from prestigious universities, collectively, the data to this point suggest that perceptual fluency prompts additional processing in general, but this processing may results in higher accuracy only for the most cognitively able.}, } @article {pmid23151255, year = {2013}, author = {Cahill, J and Paley, G and Hardy, G}, title = {What do patients find helpful in psychotherapy? Implications for the therapeutic relationship in mental health nursing.}, journal = {Journal of psychiatric and mental health nursing}, volume = {20}, number = {9}, pages = {782-791}, doi = {10.1111/jpm.12015}, pmid = {23151255}, issn = {1365-2850}, mesh = {Adult ; Cognitive Behavioral Therapy/methods/*standards ; Depression/*therapy ; Evidence-Based Nursing ; Female ; Humans ; Male ; Middle Aged ; *Nurse-Patient Relations ; *Patient Satisfaction ; Psychiatric Nursing/*standards ; Psychotherapy, Psychodynamic/methods/*standards ; Treatment Outcome ; }, abstract = {This study examined client perception of the therapeutic impact of two models of therapy delivered by mental health nurses and clinical psychologists respectively - psychodynamic interpersonal therapy (PIT) and cognitive behavioural therapy (CBT). A non-equivalent groups design was used in order to benchmark results against Llewelyn et al.: one group received PIT and the other received CBT. This design was utilized principally because the research was conducted across two practice settings where randomization was not feasible. We used two intact groups in practice research settings that received the therapies as reported in Llewelyn et al. Sixty-one clients receiving CBT or PIT in practice research settings completed a Helpful Aspects of Therapy form after each session in order to measure client perceptions of helpful and hindering events in therapy. Only two out of the 13 impacts were rated as significantly different. PIT clients reported higher levels of 'awareness' than CBT clients, whereas CBT clients reported higher levels of problem solution than PIT clients. The results replicate Llewelyn et al.'s findings in that clients experienced theoretically different models of therapy as broadly similar in their therapeutic impact. We argue that this provides some support for the influence of 'common' rather than 'specific' factors in psychotherapy effectiveness in mental health nursing.}, } @article {pmid23141894, year = {2012}, author = {Liechti, F and Dufour, JF}, title = {Treatment of NASH with ursodeoxycholic acid: cons.}, journal = {Clinics and research in hepatology and gastroenterology}, volume = {36 Suppl 1}, number = {}, pages = {S46-52}, doi = {10.1016/S2210-7401(12)70021-9}, pmid = {23141894}, issn = {2210-741X}, mesh = {Anti-Inflammatory Agents/*therapeutic use ; Cholagogues and Choleretics/*therapeutic use ; Fatty Liver/*drug therapy ; Humans ; Non-alcoholic Fatty Liver Disease ; Ursodeoxycholic Acid/*therapeutic use ; }, abstract = {Non-alcoholic steatohepatitis (NASH) has a prevalence of 1% in Western countries. Its causes as well as its medical treatment are, to date, still debated. Recently, studies of agents suggested to have antiapoptotic, insulin-sensitizing or anti-inflammatory effects in patients with NASH have been conducted, one of which is ursodeoxycholic acid (UDCA), a tertiary bile acid. Between 1994 and 2008, four prospective randomized, double-blind, placebo-controlled studies of the treatment of NASH with UDCA were conducted. The first study, by Lindor et al., compared the impact of 13-15 mg/kg/day of UDCA to a placebo. The second study by Dufour et al. had an additional third arm that administered combination therapy with UDCA and vitamin E. The third and fourth studies by Leuschner et al. and by Ratziu et al. evaluated high doses of UDCA at 25-35 mg/kg/day, and used liver biopsies and serum liver enzyme levels to evaluate the impact of UDCA. With the exception of Ratziu et al.'s study, which was lacking a second liver biopsy, none of these studies showed any significant differences in the treatment of NASH with UDCA compared with a placebo. However, Dufour et al. did observe a significant improvement of NASH with the combination (UDCA/VitE) vs placebo therapy, whereas UDCA monotherapy was not effective in the treatment of NASH. Nevertheless, the effects of other bile acids and combination therapies need to be explored.}, } @article {pmid23121792, year = {2012}, author = {Barnes, J and Prescott, T and Muncer, S}, title = {Confirmatory factor analysis for the Eating Disorder Examination Questionnaire: Evidence supporting a three-factor model.}, journal = {Eating behaviors}, volume = {13}, number = {4}, pages = {379-381}, doi = {10.1016/j.eatbeh.2012.05.001}, pmid = {23121792}, issn = {1873-7358}, mesh = {Adult ; Cross-Sectional Studies ; Factor Analysis, Statistical ; Feeding and Eating Disorders/*diagnosis ; Female ; Humans ; Male ; Models, Statistical ; Psychometrics ; Reproducibility of Results ; Students ; *Surveys and Questionnaires ; Universities ; }, abstract = {OBJECTIVE: The purpose of this investigation was to compare the goodness-of-fit of a one factor model with the four factor model proposed by Fairburn (2008) and the three factor model proposed by Peterson and colleagues (2007) for the Eating Disorder Examination Questionnaire (EDE-Q 6.0) (Fairburn and Beglin, 1994).

METHOD: Using a cross-sectional design, the EDE-Q was completed by 569 adults recruited from universities and eating disorder charities in the UK. Confirmatory factor analysis (CFA) was carried out for both the student and non-student groups.

RESULTS: CFA indicated that Peterson et al.'s (2007) three factor model was the best fit for both groups within the current data sample. Acceptable levels of internal reliability were observed and there was clear evidence for a hierarchical factor of eating disorder.

DISCUSSION: The results of this study provide support for the three factor model of the EDE-Q suggested by Peterson and colleagues (2007) in that this model was appropriate for both the student and non-student sample populations.}, } @article {pmid23112779, year = {2012}, author = {Hübner, R and Töbel, L}, title = {Does attentional selectivity in the flanker task improve discretely or gradually?.}, journal = {Frontiers in psychology}, volume = {3}, number = {}, pages = {434}, pmid = {23112779}, issn = {1664-1078}, abstract = {An important question is whether attentional selectivity improves discretely or continuously during stimulus processing. In a recent study, Hübner et al. (2010) found that the discrete Dual-Stage Two-Phase (DSTP) model accounted better for flanker-task data than various continuous-improvement models. However, in a subsequent study, White et al. (2011) introduced the continuous shrinking-spotlight (SSP) model and showed that it was superior to the DSTP model. From this result they concluded that attentional selectivity improves continuously rather than discretely. Because different stimuli and procedures were used in these two studies, though, we questioned that the superiority of the SSP model holds generally. Therefore, we fit the SSP model to Hübner et al.'s data and found that the DSTP model was again superior. A series of four experiments revealed that model superiority depends on the response-stimulus interval. Together, our results demonstrate that methodological details can be crucial for model selection, and that further comparisons between the models are needed before it can be decided whether attentional selectivity improves continuously or discretely.}, } @article {pmid23106686, year = {2013}, author = {Mattern, KD and Patterson, BF}, title = {Test of slope and intercept bias in college admissions: a response to Aguinis, Culpepper, and Pierce (2010).}, journal = {The Journal of applied psychology}, volume = {98}, number = {1}, pages = {134-147}, doi = {10.1037/a0030610}, pmid = {23106686}, issn = {1939-1854}, mesh = {Aptitude Tests/*standards ; *Behavioral Research ; *Bias ; Humans ; Personnel Selection/*standards ; }, abstract = {Research on the predictive bias of cognitive tests has generally shown (a) no slope effects and (b) small intercept effects, typically favoring the minority group. Aguinis, Culpepper, and Pierce (2010) simulated data and demonstrated that statistical artifacts may have led to a lack of power to detect slope differences and an overestimate of the size of the intercept effect. In response to Aguinis et al.'s (2010) call for a revival of predictive bias research, we used data on over 475,000 students entering college between 2006 and 2008 to estimate slope and intercept differences in the college admissions context. Corrections for statistical artifacts were applied. Furthermore, plotting of regression lines supplemented traditional analyses of predictive bias to offer additional evidence of the form and extent to which predictive bias exists. Congruent with previous research on bias of cognitive tests, using SAT scores in conjunction with high school grade-point average to predict first-year grade-point average revealed minimal differential prediction (ΔR[2]intercept ranged from .004 to .032 and ΔR[2]slope ranged from .001 to .013 depending on the corrections applied and comparison groups examined). We found, on the basis of regression plots, that college grades were consistently overpredicted for Black and Hispanic students and underpredicted for female students.}, } @article {pmid23096949, year = {2013}, author = {Ayoub, MA and Gad, HM}, title = {Neglected neck femur fractures in adolescents and young adults: factors predicting the surgical outcome.}, journal = {Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association}, volume = {18}, number = {1}, pages = {93-100}, doi = {10.1007/s00776-012-0323-8}, pmid = {23096949}, issn = {1436-2023}, mesh = {Adolescent ; Adult ; Egypt/epidemiology ; Femoral Neck Fractures/diagnostic imaging/epidemiology/*surgery ; Follow-Up Studies ; Fracture Fixation, Internal/*methods ; *Fracture Healing ; Humans ; Incidence ; Middle Aged ; *Neglected Diseases ; Postoperative Complications/*epidemiology ; Prognosis ; Radiography ; Retrospective Studies ; Risk Assessment/*methods ; Young Adult ; }, abstract = {BACKGROUND: Neglected femoral neck fracture in young adults is an intriguing problem. This retrospective study tried to solve that challenge through open reduction, cannulated screw internal fixation, autogenous iliac bone and bone marrow grafting.

METHODS: Thirty-six cases were studied; they were classified according to Sandhu et al.'s classification. Twenty cases were type I and 16 cases were type II fractures; the mean age was 26.8 years; fracture neglect averaged 44.6 days. Twenty cases had posterior comminution and 16 cases had anterior comminution. All cases had open reduction, cannulated screw internal fixation, autogenous iliac bone and bone marrow grafting. The Harris hip score and Matta et al. grading system were applied for functional and radiological evaluation, respectively.

RESULTS: The average postoperative follow-up was 25.3 months; 94.4 % of the cases had solid union in a mean of 19.6 weeks. Functionally, the Harris hip score averaged 87.8 points. Nonunion, avascular necrosis and coxa vara complicated two, two and four cases, respectively. Fair and poor radiological results were related to coxa vara and avascular necrosis, respectively. Nonunion was significantly related to posterior comminution, type II neglected fracture, and a neglect of more than 45 days. Age groups more than 30 years old and postoperative neck-shaft angles <140° were significantly associated with late-onset radiological healing and nonunion.

CONCLUSIONS: Cannulated screw osteosynthesis augmented by autogenous bone and bone marrow grafting is a simple, easy-to-perform surgical procedure with encouraging clinical outcomes for selected patients complaining of that difficult problem.}, } @article {pmid23094474, year = {2012}, author = {Steele, JP and Rupayana, DD and Mills, MJ and Smith, MR and Wefald, A and Downey, RG}, title = {Relative importance and utility of positive worker states: a review and empirical examination.}, journal = {The Journal of psychology}, volume = {146}, number = {6}, pages = {617-650}, doi = {10.1080/00223980.2012.665100}, pmid = {23094474}, issn = {0022-3980}, mesh = {Adolescent ; Adult ; Data Collection ; Employee Performance Appraisal ; Female ; Humans ; Intention ; *Job Satisfaction ; Male ; Motivation ; *Organizational Culture ; Personnel Loyalty ; Personnel Turnover ; Quality of Life ; Restaurants ; *Social Support ; Young Adult ; }, abstract = {Our purpose was to identity the unique contribution, relative importance, and utility of positive worker states. Using Luthans et al.'s (2007) five positive organizational behavior criteria, a variety of positive worker states were reviewed and then empirically tested to establish if they met these criteria. Data were collected from 724 restaurant employees. Positive worker states included: job involvement, perceived organizational support, engagement, and vigor. Criteria were self-reported performance, customer service, turnover intention, satisfaction, and quality of life. Our review indicated consistency between predictor adequacy of meeting the criteria and their empirical relationship with key outcomes. This research found the positive worker states to be independent constructs that had differential effects depending on the focused outcome. Regression and relative weights analyses showed involvement was a weak predictor of outcomes, while perceived organizational support was the most consistent predictor. Vigor was most useful when predicting job performance. Quality of life was poorly explained.}, } @article {pmid23075065, year = {2012}, author = {Rogers, SM}, title = {Mapping the genomic architecture of ecological speciation in the wild: does linkage disequilibrium hold the key?.}, journal = {Molecular ecology}, volume = {21}, number = {21}, pages = {5155-5158}, doi = {10.1111/mec.12019}, pmid = {23075065}, issn = {1365-294X}, mesh = {Adaptation, Physiological/*genetics ; Animals ; *Hybridization, Genetic ; Male ; Smegmamorpha/*genetics ; }, abstract = {The hunt for the genes underlying ecological speciation has now closed in on a number of candidates, but making the link from genotype to phenotype continues to pose a significant challenge. This is partly because genetic studies in many systems remain impeded by long generation times or an inability to perform controlled crosses. Now, in this issue of Molecular Ecology, Malek et al. (2012) demonstrate the utility of a novel admixture mapping approach that can be used to identify genomic regions contributing to adaptive trait divergence between natural populations. Remarkably, they validate their approach by mapping traits associated with mate choice in a wild limnetic and benthic threespine stickleback (Gasterosteus aculeatus) species pair, finding several loci associated with male nuptial coloration and shape. While this study benefited from tried-and-true microsatellites in a well-characterized species with a detailed genetic map (and genome sequence), the field is quickly moving towards the use of next-generation sequencing, especially for nonmodel systems. The ability to characterize molecular polymorphisms for any system suggests that molecular ecologists working on virtually any species may benefit from applying Malek et al.'s approach, if naturally admixed populations are available.}, } @article {pmid23069915, year = {2012}, author = {Shourgashti, Z and Keshvari, H}, title = {Comment on Blasi et al.'s (2011) "Lipid nanoparticles for brain targeting I. Formulation optimization".}, journal = {International journal of pharmaceutics}, volume = {439}, number = {1-2}, pages = {169-70; author reply 171-4}, doi = {10.1016/j.ijpharm.2012.10.006}, pmid = {23069915}, issn = {1873-3476}, mesh = {Brain/*metabolism ; *Drug Delivery Systems ; Lipids/*chemistry ; *Nanoparticles ; Triglycerides/*administration & dosage ; }, } @article {pmid23066234, year = {2012}, author = {Prabu, NM and Kohila, K and Sivaraj, S and Prabu, PS}, title = {Appraisal of the cephalometric norms for the upper and lower lips of the South Indian ethnic population.}, journal = {Journal of pharmacy & bioallied sciences}, volume = {4}, number = {Suppl 2}, pages = {S136-8}, pmid = {23066234}, issn = {0975-7406}, abstract = {AIM: The guidelines for planning an improvement in the facial appearance till recently existed in the form of evaluation of linear and angular parameters and ratios related to the hard tissues in the various cephalometric analyses. The present study aimed at establishing Arnett et al.'s norms of the upper and lower lip for the local population and assessing the extent by which these differ from the original norms proposed by Arnett et al.

MATERIALS AND METHODS: Forty pretreatment lateral cephalograms (20 males and 20 females) with normal occlusion and well-balanced face were chosen for this study. Upper and lower lip lengths, thicknesses, and chin thickness were all measured according to soft tissue cephalometric analysis by Arnett et al.

RESULTS: The obtained data were statistically analyzed and compared with other studies.

CONCLUSION: Males had thicker and longer upper and lower lips when compared to females, but they were comparatively thinner than the results of Arnett et al. Females had more interlabial gap than males. The difference in soft tissue parameters in different ethnic groups shows the importance of defining what is optimal for a particular group.}, } @article {pmid23062329, year = {2013}, author = {Calabrese, E and Hanauer, SB}, title = {Reply to Dr Kountouras et al.'s letter.}, journal = {Journal of Crohn's & colitis}, volume = {7}, number = {6}, pages = {515}, doi = {10.1016/j.crohns.2012.09.019}, pmid = {23062329}, issn = {1876-4479}, mesh = {Colitis, Ulcerative/*drug therapy ; Female ; Humans ; Male ; Nicotine/*therapeutic use ; Nicotinic Agonists/*therapeutic use ; *Smoking ; }, } @article {pmid23060778, year = {2012}, author = {Newcombe, PI and Campbell, C and Siakaluk, PD and Pexman, PM}, title = {Effects of emotional and sensorimotor knowledge in semantic processing of concrete and abstract nouns.}, journal = {Frontiers in human neuroscience}, volume = {6}, number = {}, pages = {275}, pmid = {23060778}, issn = {1662-5161}, abstract = {There is much empirical evidence that words' relative imageability and body-object interaction (BOI) facilitate lexical processing for concrete nouns (e.g., Bennett et al., 2011). These findings are consistent with a grounded cognition framework (e.g., Barsalou, 2008), in which sensorimotor knowledge is integral to lexical processing. In the present study, we examined whether lexical processing is also sensitive to the dimension of emotional experience (i.e., the ease with which words evoke emotional experience), which is also derived from a grounded cognition framework. We examined the effects of emotional experience, imageability, and BOI in semantic categorization for concrete and abstract nouns. Our results indicate that for concrete nouns, emotional experience was associated with less accurate categorization, whereas imageability and BOI were associated with faster and more accurate categorization. For abstract nouns, emotional experience was associated with faster and more accurate categorization, whereas BOI was associated with slower and less accurate categorization. This pattern of results was observed even with many other lexical and semantic dimensions statistically controlled. These findings are consistent with Vigliocco et al.'s (2009) theory of semantic representation, which states that emotional knowledge underlies meanings for abstract concepts, whereas sensorimotor knowledge underlies meanings for concrete concepts.}, } @article {pmid23056360, year = {2012}, author = {You, W and Zhang, Q and Verdonschot, RG}, title = {Masked syllable priming effects in word and picture naming in Chinese.}, journal = {PloS one}, volume = {7}, number = {10}, pages = {e46595}, pmid = {23056360}, issn = {1932-6203}, mesh = {Adolescent ; Adult ; Animals ; China ; Humans ; *Language ; Young Adult ; }, abstract = {Four experiments investigated the role of the syllable in Chinese spoken word production. Chen, Chen and Ferrand (2003) reported a syllable priming effect when primes and targets shared the first syllable using a masked priming paradigm in Chinese. Our Experiment 1 was a direct replication of Chen et al.'s (2003) Experiment 3 employing CV (e.g., ,/ba2.ying2/, strike camp) and CVG (e.g., ,/bai2.shou3/, white haired) syllable types. Experiment 2 tested the syllable priming effect using different syllable types: e.g., CV (,/qi4.qiu2/, balloon) and CVN (,/qing1.ting2/, dragonfly). Experiment 3 investigated this issue further using line drawings of common objects as targets that were preceded either by a CV (e.g., ,/qi3/, attempt), or a CVN (e.g., ,/qing2/, affection) prime. Experiment 4 further examined the priming effect by a comparison between CV or CVN priming and an unrelated priming condition using CV-NX (e.g., ,/mi2.ni3/, mini) and CVN-CX (e.g., ,/min2.ju1/, dwellings) as target words. These four experiments consistently found that CV targets were named faster when preceded by CV primes than when they were preceded by CVG, CVN or unrelated primes, whereas CVG or CVN targets showed the reverse pattern. These results indicate that the priming effect critically depends on the match between the structure of the prime and that of the first syllable of the target. The effect obtained in this study was consistent across different stimuli and different tasks (word and picture naming), and provides more conclusive and consistent data regarding the role of the syllable in Chinese speech production.}, } @article {pmid23051901, year = {2014}, author = {Michl, P and Meindl, T and Meister, F and Born, C and Engel, RR and Reiser, M and Hennig-Fast, K}, title = {Neurobiological underpinnings of shame and guilt: a pilot fMRI study.}, journal = {Social cognitive and affective neuroscience}, volume = {9}, number = {2}, pages = {150-157}, pmid = {23051901}, issn = {1749-5024}, mesh = {Adult ; Brain/*physiology ; Brain Mapping ; Emotions/*physiology ; Female ; *Guilt ; Humans ; Imagination/*physiology ; Magnetic Resonance Imaging ; Male ; Neural Pathways/physiology ; Pattern Recognition, Visual/physiology ; Pilot Projects ; Reading ; Sex Factors ; *Shame ; Young Adult ; }, abstract = {In this study, a functional magnetic resonance imaging paradigm originally employed by Takahashi et al. was adapted to look for emotion-specific differences in functional brain activity within a healthy German sample (N = 14), using shame- and guilt-related stimuli and neutral stimuli. Activations were found for both of these emotions in the temporal lobe (shame condition: anterior cingulate cortex, parahippocampal gyrus; guilt condition: fusiform gyrus, middle temporal gyrus). Specific activations were found for shame in the frontal lobe (medial and inferior frontal gyrus), and for guilt in the amygdala and insula. This is consistent with Takahashi et al.'s results obtained for a Japanese sample (using Japanese stimuli), which showed activations in the fusiform gyrus, hippocampus, middle occipital gyrus and parahippocampal gyrus. During the imagination of shame, frontal and temporal areas (e.g. middle frontal gyrus and parahippocampal gyrus) were responsive regardless of gender. In the guilt condition, women only activate temporal regions, whereas men showed additional frontal and occipital activation as well as a responsive amygdala. The results suggest that shame and guilt share some neural networks, as well as having individual areas of activation. It can be concluded that frontal, temporal and limbic areas play a prominent role in the generation of moral feelings.}, } @article {pmid23041505, year = {2012}, author = {Daar, M and Or, CC and Wilson, HR}, title = {Increment thresholds for radial frequency trajectories produce a dipper function.}, journal = {Vision research}, volume = {73}, number = {}, pages = {46-52}, doi = {10.1016/j.visres.2012.09.010}, pmid = {23041505}, issn = {1878-5646}, mesh = {Adult ; Attention/*physiology ; *Cues ; Discrimination, Psychological/*physiology ; Female ; Form Perception/*physiology ; Humans ; Male ; Motion Perception/*physiology ; Pattern Recognition, Visual/*physiology ; Photic Stimulation ; Sensory Thresholds ; Space Perception/*physiology ; }, abstract = {Radial frequency (RF) trajectories are a new class of stimuli that have been developed to study the visual perception of periodic motion (Or et al., 2011). These stimuli are described by a moving dot that traces a distorted path through space with periodic radial deformations whose frequency, amplitude, and phase can be independently specified. Here, we extend Or et al.'s findings by investigating how the discrimination of RF amplitude changes as a function of different reference amplitudes in a two-interval forced choice task. Using an RF3 trajectory (a pattern with three cycles of deformation along its trajectory), increment thresholds were measured at six different reference amplitudes: Detection (discriminating a circle from RF3), 1X (discriminating a pair of RF3 patterns, with the amplitude of one member of this pair set to (1X) threshold obtained from the detection condition), 2.5X, 5X, 10X, and 15X. Data show that sensitivity to changes in amplitude improves at 2.5X by a factor of about 2, recovers to detection threshold levels at 5X, and continues to rise at 10X and 15X. These results generalize across both radial frequency and the angular speed of the trajectory, and persist with low contrast trajectories. Our findings point to the existence of a neural mechanism that is sensitive to deviations from circular motion trajectories.}, } @article {pmid23040291, year = {2013}, author = {Andrisani, G and Armuzzi, A}, title = {Reply to Dr. Joob et al.'s letter.}, journal = {Journal of Crohn's & colitis}, volume = {7}, number = {4}, pages = {e154}, doi = {10.1016/j.crohns.2012.09.008}, pmid = {23040291}, issn = {1876-4479}, mesh = {Anti-Inflammatory Agents, Non-Steroidal/*therapeutic use ; Antibodies, Monoclonal/*therapeutic use ; Colitis, Ulcerative/*drug therapy ; Humans ; Infliximab ; Male ; Pyoderma Gangrenosum/*drug therapy/*surgery ; }, } @article {pmid23035647, year = {2012}, author = {Liversidge, HM}, title = {The assessment and interpretation of Demirjian, Goldstein and Tanner's dental maturity.}, journal = {Annals of human biology}, volume = {39}, number = {5}, pages = {412-431}, doi = {10.3109/03014460.2012.716080}, pmid = {23035647}, issn = {1464-5033}, mesh = {Age Determination by Teeth/*methods ; Female ; Humans ; Male ; Radiography, Panoramic ; Sex Characteristics ; Tooth/*growth & development ; Tooth Calcification/*physiology ; }, abstract = {BACKGROUND: A frequently reported advancement in dental maturity compared with the 50(th) percentile of Demirjian, Goldstein and Tanner (1973, Hum Biol 45:211-27) has been interpreted as a population difference.

AIM: To review the assessment and interpretation of Demirjian et al.'s dental maturity.

SUBJECTS AND METHODS: Dental maturity of boys from published reports was compared as maturity curves and difference to the 50(th) percentile in terms of chronological age and score. Dental maturity, as well as maturity of individual teeth, was compared in the fastest and slowest maturing groups of boys from the Chaillet database.

RESULTS: Maturity curves from published reports by age category were broadly similar and differences occurred at the steepest part of the curve. These reduced when expressed as score rather than age. Many studies report a higher than expected score for chronological age and the database contained more than expected children with scores>97(th) percentile. Revised scores for chronological age from this database were calculated (4072 males, 3958 females, aged 2.1-17.9).

CONCLUSION: Most published reports were similar to the database smoothed maturity curve. This method of dental maturity is designed to assess maturity for a single child and is unsuitable to compare groups.}, } @article {pmid23034110, year = {2012}, author = {Hills, PJ and Sullivan, AJ and Pake, JM}, title = {Aberrant first fixations when looking at inverted faces in various poses: the result of the centre-of-gravity effect?.}, journal = {British journal of psychology (London, England : 1953)}, volume = {103}, number = {4}, pages = {520-538}, doi = {10.1111/j.2044-8295.2011.02091.x}, pmid = {23034110}, issn = {2044-8295}, mesh = {Adolescent ; Adult ; Eye Movements/physiology ; *Face ; Female ; Fixation, Ocular/*physiology ; Humans ; Male ; Middle Aged ; Orientation/*physiology ; Pattern Recognition, Visual/*physiology ; Recognition, Psychology/*physiology ; Young Adult ; }, abstract = {Face recognition is essential in everyday human life, and all faces are encountered in different poses. However, when a face is inverted, difficulties arise for recognition and eye movements may (Barton, Radcliffe, Cherkasova, Edleman, & Intriligator, 2006) or may not be disrupted (Williams & Henderson, 2007). The present study explored the effects of orientation and pose on recognition and eye movements during a standard old/new recognition task in order to resolve whether inversion disrupts eye movements. Eye-tracking data looked at the first fixations, the number of fixations, and the duration of fixations over a face. A standard inversion effect was observed, but the three-quarter view advantage was not observed. Eye-movement data revealed that the eyes were the most sampled feature (in terms of first fixation, number of fixations, and duration of fixation) for all upright faces, however, other features were sampled first for inverted faces. These results are consistent with Barton et al.'s (2006) but not Williams and Henderson's (2007) findings: possible explanations for this are discussed with the caveat that the same images were used from learning to test.}, } @article {pmid23021023, year = {2012}, author = {Telles, LE and Folino, JO and Taborda, JG}, title = {Accuracy of the Historical, Clinical and Risk Management Scales (HCR-20) in predicting violence and other offenses in forensic psychiatric patients in Brazil.}, journal = {International journal of law and psychiatry}, volume = {35}, number = {5-6}, pages = {427-431}, doi = {10.1016/j.ijlp.2012.09.001}, pmid = {23021023}, issn = {1873-6386}, mesh = {Adult ; Brazil ; Checklist/standards ; Forecasting ; *Forensic Psychiatry ; Humans ; Logistic Models ; Male ; *Predictive Value of Tests ; Prospective Studies ; Reproducibility of Results ; Risk Assessment/methods ; Surveys and Questionnaires/*standards ; Violence/*trends ; }, abstract = {BACKGROUND: Assessing the risk of violence is a complex task. In Latin America it is often based on clinical criteria that are not very objective or structured. HCR-20 has been used to increase the accuracy of this exam.

AIMS: The aim of this study was to examine the predictive validity of the Historical, Clinical and Risk Management Scales (HCR-20) violence risk assessment scale on a sample of Brazilian male forensic psychiatric inpatients.

METHOD: A concurrent prospective cohort design was used. The cohort was selected among the population of inpatients in Unit D (N=68) at Instituto Psiquiátrico Forense Mauricio Cardoso (IPF), Brazil. For the baseline assessment the following instruments: HCR-20-Assessing Risk for Violence, Version 2, and Hare Psychopathy Checklist, Revised (PCL-R) were used. During the one-year follow up, episodes of violent and/or anti-social behavior were assessed, and recorded on the Yudofsky's Overt Aggression Scale (OAS) and Tengström et al.'s Follow-Up Questionnaire. The accuracy of HCR-20 and PCL-R to predict violent and/or anti-social behavior was assessed.

RESULTS AND CONCLUSIONS: For the whole cohort, the mean total score of PCL-R was 13.54 and of HCR-20 it was 23.32. The rate of recidivism in the twelve month follow up was 73.5%. Outstanding among the risk factors explored for their predictive efficacy are scale HCR-20 and subscale H for any event, and scale HCR-20 for a violent event. The predictive efficacy of scales HCR-20 and PCL-R was greater for any antisocial event than for a violent event. By taking into account the possibility of recidivism and the probability of recidivism accumulated over time, instruments HCR-20 and PCL-R behaved as expected. In all these explorations, the instruments significantly differentiated the group of the sample that recidivated earlier.}, } @article {pmid23008145, year = {2012}, author = {Bilgic, B and Setsompop, K and Cohen-Adad, J and Yendiki, A and Wald, LL and Adalsteinsson, E}, title = {Accelerated diffusion spectrum imaging with compressed sensing using adaptive dictionaries.}, journal = {Magnetic resonance in medicine}, volume = {68}, number = {6}, pages = {1747-1754}, pmid = {23008145}, issn = {1522-2594}, support = {K99 EB008129/EB/NIBIB NIH HHS/United States ; U01MH093765/MH/NIMH NIH HHS/United States ; U01 MH093765/MH/NIMH NIH HHS/United States ; K99EB012107/EB/NIBIB NIH HHS/United States ; R01EB006847/EB/NIBIB NIH HHS/United States ; P41 RR014075/RR/NCRR NIH HHS/United States ; K99 EB012107/EB/NIBIB NIH HHS/United States ; R00 EB012107/EB/NIBIB NIH HHS/United States ; R01 EB007942/EB/NIBIB NIH HHS/United States ; R01 EB006847/EB/NIBIB NIH HHS/United States ; K99/R00 EB008129/EB/NIBIB NIH HHS/United States ; R00 EB008129/EB/NIBIB NIH HHS/United States ; P41RR14075/RR/NCRR NIH HHS/United States ; }, mesh = {Algorithms ; Brain/*cytology ; Data Compression/*methods ; Diffusion Tensor Imaging/*methods ; Humans ; Image Enhancement/*methods ; Image Interpretation, Computer-Assisted/*methods ; Nerve Fibers, Myelinated/*ultrastructure ; Pattern Recognition, Automated/*methods ; Reproducibility of Results ; Sensitivity and Specificity ; }, abstract = {Diffusion spectrum imaging offers detailed information on complex distributions of intravoxel fiber orientations at the expense of extremely long imaging times (∼1 h). Recent work by Menzel et al. demonstrated successful recovery of diffusion probability density functions from sub-Nyquist sampled q-space by imposing sparsity constraints on the probability density functions under wavelet and total variation transforms. As the performance of compressed sensing reconstruction depends strongly on the level of sparsity in the selected transform space, a dictionary specifically tailored for diffusion probability density functions can yield higher fidelity results. To our knowledge, this work is the first application of adaptive dictionaries in diffusion spectrum imaging, whereby we reduce the scan time of whole brain diffusion spectrum imaging acquisition from 50 to 17 min while retaining high image quality. In vivo experiments were conducted with the 3T Connectome MRI. The root-mean-square error of the reconstructed "missing" diffusion images were calculated by comparing them to a gold standard dataset (obtained from acquiring 10 averages of diffusion images in these missing directions). The root-mean-square error from the proposed reconstruction method is up to two times lower than that of Menzel et al.'s method and is actually comparable to that of the fully-sampled 50 minute scan. Comparison of tractography solutions in 18 major white-matter pathways also indicated good agreement between the fully-sampled and 3-fold accelerated reconstructions. Further, we demonstrate that a dictionary trained using probability density functions from a single slice of a particular subject generalizes well to other slices from the same subject, as well as to slices from other subjects.}, } @article {pmid23006568, year = {2013}, author = {Niraimathi, KL and Sudha, V and Lavanya, R and Brindha, P}, title = {Biosynthesis of silver nanoparticles using Alternanthera sessilis (Linn.) extract and their antimicrobial, antioxidant activities.}, journal = {Colloids and surfaces. B, Biointerfaces}, volume = {102}, number = {}, pages = {288-291}, doi = {10.1016/j.colsurfb.2012.08.041}, pmid = {23006568}, issn = {1873-4367}, mesh = {Anti-Infective Agents/*chemistry/pharmacology ; Antioxidants/*chemistry ; Ascorbic Acid/chemistry ; Metal Nanoparticles/*chemistry/ultrastructure ; Microscopy, Electron, Scanning ; Silver/*chemistry ; Spectroscopy, Fourier Transform Infrared ; }, abstract = {The present work focuses the use of the aqueous extract of Alternanthera sessilis Linn. (Amaranthaceae) in producing silver nanoparticles (AgNPs) from silver nitrate aqueous. Phytochemical analysis of the extract revealed the presence of alkaloid, tannins, ascorbic acid, carbohydrates and proteins and they serve as effective reducing and capping agents for converting silver nitrate into nanoparticles. The synthesized silver nanoparticles (AgNPs) were also tested for proteins and ascorbic acid. Its pH was also determined (5.63). The AgNPs obtained was characterized by UV-vis spectroscopy, FT-IR spectroscopy, SEM, Zeta sizer and TG-DSC. SEM images which revealed the presence of various shapes and sizes. FT-IR spectrum showed the AgNPs having a coating of proteins indicating a dual role of bio-molecules responsible for capping and efficient stabilization of the silver nanoparticles. Presence of impurities and melting point profile were screened by TG-DSC analyzer. AgNPs were synthesized from the silver nitrate through the reducing power of ascorbic acid present in A. sessilis leaves. In this study, we also investigated antimicrobial and antioxidant activity of green synthesized AgNPs. The antimicrobial activity is investigated by Bauer et al.'s method. Antioxidant activity was done by DPPH method.}, } @article {pmid23002784, year = {2012}, author = {Baldwin, SA and Imel, ZE and Atkins, DC}, title = {The influence of therapist variance on the dependability of therapists' alliance scores: a brief comment on "The dependability of alliance assessments: the alliance-outcome correlation is larger than you think" (Crits-Christoph et al., 2011).}, journal = {Journal of consulting and clinical psychology}, volume = {80}, number = {5}, pages = {947-951}, doi = {10.1037/a0027935}, pmid = {23002784}, issn = {1939-2117}, mesh = {Depressive Disorder, Major/*therapy ; Female ; Humans ; Male ; *Professional-Patient Relations ; *Psychotherapy ; }, abstract = {OBJECTIVE: Crits-Christoph, Connolly Gibbons, Hamilton, Ring-Kurtz, and Gallop (2011) used generalizability theory to critique the measurement of the therapeutic alliance in psychotherapy research, showing that the dependability of alliance scores may be quite low, which in turn can lead to attenuated alliance-outcome correlation estimates.

METHOD AND RESULTS: Two extensions to Crits-Christoph et al.'s critique are presented that can greatly influence dependability of therapist scores and are particularly relevant to researchers wishing to study process-outcome correlations at the therapist level. Specifically, the authors show how the intraclass correlation and the number of therapists affect both the magnitude and precision of generalizability coefficients.

CONCLUSIONS: The authors note that attending to issues raised in this article and Crits-Christoph et al. (2011) in future process-outcome research will improve the accuracy of the conclusions about process-outcome correlations.}, } @article {pmid22994286, year = {2012}, author = {Smith, EE and Myers, N and Sethi, U and Pantazatos, S and Yanagihara, T and Hirsch, J}, title = {Conceptual representations of perceptual knowledge.}, journal = {Cognitive neuropsychology}, volume = {29}, number = {3}, pages = {237-248}, pmid = {22994286}, issn = {1464-0627}, support = {5F31MH088104-03/MH/NIMH NIH HHS/United States ; AG015116-12/AG/NIA NIH HHS/United States ; R01 AG015116/AG/NIA NIH HHS/United States ; F31 MH088104/MH/NIMH NIH HHS/United States ; 5T32GM007367-34/GM/NIGMS NIH HHS/United States ; }, mesh = {Adult ; Brain Mapping/methods/*psychology ; Female ; Frontal Lobe/*physiology ; Functional Laterality/*physiology ; Humans ; Magnetic Resonance Imaging/methods/psychology ; Male ; Neural Pathways/physiology ; Perception/*physiology ; Psychomotor Performance/*physiology ; Reaction Time/physiology ; Semantics ; Temporal Lobe/*physiology ; }, abstract = {Many neuroimaging studies of semantic memory have argued that knowledge of an object's perceptual properties are represented in a modality-specific manner. These studies often base their argument on finding activation in the left-hemisphere fusiform gyrus-a region assumed to be involved in perceptual processing-when the participant is verifying verbal statements about objects and properties. In this paper, we report an extension of one of these influential papers-Kan, Barsalou, Solomon, Minor, and Thompson-Schill (2003)-and present evidence for an amodal component in the representation and processing of perceptual knowledge. Participants were required to verify object-property statements (e.g., "cat-whiskers?"; "bear-wings?") while they were being scanned by functional magnetic resonance imaging (fMRI). We replicated Kan et al.'s activation in the left fusiform gyrus, but also found activation in regions of left inferior frontal gyrus (IFG) and middle-temporal gyrus, areas known to reflect amodal processes or representations. Further, only activations in the left IFG, an amodal area, were correlated with measures of behavioural performance.}, } @article {pmid22990229, year = {2013}, author = {Lund, I and Scheffels, J}, title = {The relative risk to health from snus and cigarettes: response to Grimsrud et al.'s commentary on "perceptions of the relative harmfulness of snus among Norwegian general practitioners and their effect on the tendency to recommend snus in smoking cessation".}, journal = {Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco}, volume = {15}, number = {1}, pages = {304-305}, pmid = {22990229}, issn = {1469-994X}, mesh = {General Practitioners/*psychology ; *Health Knowledge, Attitudes, Practice ; Humans ; Smoking Cessation/*methods ; Tobacco, Smokeless/*adverse effects ; }, } @article {pmid22985381, year = {2012}, author = {Fehlings, MG and Wilson, JR and Frankowski, RF and Toups, EG and Aarabi, B and Harrop, JS and Shaffrey, CI and Harkema, SJ and Guest, JD and Tator, CH and Burau, KD and Johnson, MW and Grossman, RG}, title = {Riluzole for the treatment of acute traumatic spinal cord injury: rationale for and design of the NACTN Phase I clinical trial.}, journal = {Journal of neurosurgery. Spine}, volume = {17}, number = {1 Suppl}, pages = {151-156}, doi = {10.3171/2012.4.AOSPINE1259}, pmid = {22985381}, issn = {1547-5646}, mesh = {Humans ; Neuroprotective Agents/*therapeutic use ; *Research Design ; Riluzole/*therapeutic use ; Spinal Cord Injuries/*drug therapy ; }, abstract = {In the immediate period after traumatic spinal cord injury (SCI) a variety of secondary injury mechanisms combine to gradually expand the initial lesion size, potentially leading to diminished neurological outcomes at long-term follow-up. Riluzole, a benzothiazole drug, which has neuroprotective properties based on sodium channel blockade and mitigation of glutamatergic toxicity, is currently an approved drug that attenuates the extent of neuronal degeneration in patients with amyotrophic lateral sclerosis. Moreover, several preclinical SCI studies have associated riluzole administration with improved functional outcomes and increased neural tissue preservation. Based on these findings, riluzole has attracted considerable interest as a potential neuroprotective drug for the treatment of SCI. Currently, a Phase I trial evaluating the safety and pharmacokinetic profile of riluzole in human SCI patients is being conducted by the North American Clinical Trials Network (NACTN) for Treatment of Spinal Cord Injury. The current review summarizes the existing preclinical and clinical literature on riluzole, provides a detailed description of the Phase I trial, and suggests potential opportunities for future investigation. Clinical trial registration no.: NCT00876889.}, } @article {pmid22982622, year = {2012}, author = {Mok, LW}, title = {Short-term retrospective versus prospective memory processing as emergent properties of the mind and brain: human fMRI evidence.}, journal = {Neuroscience}, volume = {226}, number = {}, pages = {236-252}, doi = {10.1016/j.neuroscience.2012.09.005}, pmid = {22982622}, issn = {1873-7544}, mesh = {Adult ; Brain/*physiology ; Brain Mapping ; Choice Behavior/physiology ; Cues ; Data Interpretation, Statistical ; Discrimination, Psychological/physiology ; Female ; Humans ; Image Processing, Computer-Assisted ; Learning/physiology ; Magnetic Resonance Imaging/*methods ; Male ; Memory/*physiology ; Practice, Psychological ; Prefrontal Cortex/physiology ; Psychomotor Performance/physiology ; Visual Perception/physiology ; Young Adult ; }, abstract = {The functional-neuroanatomical substrates for short-term retrospective versus prospective memory processing were examined in a delay task, in which associative choices were made conditionally based on the presenting discriminative/cue stimulus. Delay-period prospection could be of the intended choice and/or the expected response outcome, whereas delay-period retrospection would be of the just-presented cue stimulus. Previous results have shown that the spontaneous process of unique outcome prospection did not implicate the lateral prefrontal cortex (PFC) but instead implicated the lateral posterior parietal cortex (LPPC) in a modality-independent fashion (Mok et al., 2009). Spontaneous retrospection was more dependent on the medial temporal lobe (MTL). Nevertheless, it was anticipated that the more explicit process of prospecting an intended choice would implicate the lateral PFC. To verify this, Mok et al.'s data were further analyzed, with new control data. Healthy, young adults performed delayed discriminative choices under procedures that biased them toward different degrees of delay-period prospection: higher-using cue-unique, differential outcomes (DO); versus lower-using a non-unique, common outcome (CO), or unpredictable, non-differential outcomes (NDO). Experimental participants performed the DO versus CO procedures concurrently, while undergoing event-related functional magnetic resonance imaging (fMRI). Separately, control participants provided data for: the NDO condition; related comparison tasks, which biased them toward different degrees of delay-period retrospection; and null-event trials. Expectedly, the more explicit process of prospecting an intended associative choice implicated the lateral PFC, as part of and together with other components of the multiple-demand network. Comparisons against null-event trials indicated that the sustained delay activity observed in MTL and LPPC, respectively, was part of default brain activity. These results demonstrated that short-term retrospection and prospection may emerge without necessarily relying on working memory-specific brain networks. Furthermore, attention may not necessarily be recruited to realize working memory. When cognitive processes are spontaneously experienced, they may be facilitated by the default brain network.}, } @article {pmid22956682, year = {2013}, author = {Goodwin, L and Fairclough, SH and Poole, HM}, title = {A cognitive-perceptual model of symptom perception in males and females: the roles of negative affect, selective attention, health anxiety and psychological job demands.}, journal = {Journal of health psychology}, volume = {18}, number = {6}, pages = {848-857}, doi = {10.1177/1359105312456321}, pmid = {22956682}, issn = {1461-7277}, mesh = {Adult ; *Affect ; Anxiety/etiology/*psychology ; *Attention ; Attitude to Health ; Employment/*psychology ; Female ; Health Behavior ; *Health Status ; Humans ; Male ; Sex Factors ; Surveys and Questionnaires ; }, abstract = {Kolk et al.'s model of symptom perception underlines the effects of trait negative affect, selective attention and external stressors. The current study tested this model in 263 males and 498 females from an occupational sample. Trait negative affect was associated with symptom reporting in females only, and selective attention and psychological job demands were associated with symptom reporting in both genders. Health anxiety was associated with symptom reporting in males only. Future studies might consider the inclusion of selective attention, which was more strongly associated with symptom reporting than negative affect. Psychological job demands appear to influence symptom reporting in both males and females.}, } @article {pmid22952431, year = {2012}, author = {Harmon, LJ}, title = {An inordinate fondness for eukaryotic diversity.}, journal = {PLoS biology}, volume = {10}, number = {8}, pages = {e1001382}, pmid = {22952431}, issn = {1545-7885}, mesh = {*Biodiversity ; Eukaryota/*genetics ; *Phylogeny ; }, abstract = {Why do some groups of organisms, like beetles, have so many species, and others, like the tuataras, so few? This classic question in evolutionary biology has a deep history and has been studied using both fossils and phylogenetic trees. Phylogeny-based studies have focused on tree balance, which compares the number of species across clades of the same age in the tree. These studies have suggested that rates of speciation and extinction vary tremendously across the tree of life. In this issue, Rabosky et al. report the most ambitious study to date on the differences in species diversity across clades in the tree of life. The authors bring together a tremendously large dataset of multicellular eukaryotes, including all living species of plants, animals, and fungi; they divide these organisms into 1,397 clades, accounting for more than 1.2 million species in total. Rabosky et al. find tremendous variation in diversity across the tree of life. There are old clades with few species, young clades with many species, and everything in between. They also note a peculiar aspect of their data: it is difficult or impossible to predict how many species will be found in a particular clade knowing how long a clade has been diversifying from a common ancestor. This pattern suggests complex dynamics of speciation and extinction in the history of eukaryotes. Rabosky et al.'s paper represents the latest development in our efforts to understand the Earth's biodiversity at the broadest scales.}, } @article {pmid22925140, year = {2012}, author = {Bergman, ME and Payne, SC and Boswell, WR}, title = {Sometimes pursuits don't pan out: anticipated destinations and other caveats: comment on Hom, Mitchell, Lee, and Griffeth (2012).}, journal = {Psychological bulletin}, volume = {138}, number = {5}, pages = {865-870}, doi = {10.1037/a0028541}, pmid = {22925140}, issn = {1939-1455}, mesh = {*Attitude ; Employment/*psychology ; Humans ; *Models, Psychological ; *Motivation ; *Personnel Turnover ; *Research Design ; }, abstract = {Hom, Mitchell, Lee, and Griffeth (2012) presented an extensive review of employee turnover research, reconceptualized the turnover criterion to include multiple destinations, and proposed to expand the predictor domain. They illuminated the multiple destinations employees pursue following turnover. By crossing desire to remain and volitional control dimensions, Hom et al. defined and described 4 withdrawal states (or predeparture mind-sets). This commentary begins by introducing the issue that people do not know precisely where they will turn over to until they have actually gone. This suggests that researchers should consider anticipated destinations when conducting research on withdrawal states. We note the limitations of measuring withdrawal states as taxonomic categories; instead, we advocate for measuring the underlying continuous dimensions of desire and control or the weight associated with the pressures to leave or stay. Finally, we highlight some temporal considerations, as withdrawal states are temporary and there is much to be learned from studying changes in such states. We conclude with some directions for future turnover research based on Hom et al.'s contribution.}, } @article {pmid22924598, year = {2012}, author = {Schimmack, U}, title = {The ironic effect of significant results on the credibility of multiple-study articles.}, journal = {Psychological methods}, volume = {17}, number = {4}, pages = {551-566}, doi = {10.1037/a0029487}, pmid = {22924598}, issn = {1939-1463}, mesh = {Humans ; Psychology/*methods ; *Publication Bias ; *Research Design ; Sample Size ; *Statistics as Topic ; }, abstract = {Cohen (1962) pointed out the importance of statistical power for psychology as a science, but statistical power of studies has not increased, while the number of studies in a single article has increased. It has been overlooked that multiple studies with modest power have a high probability of producing nonsignificant results because power decreases as a function of the number of statistical tests that are being conducted (Maxwell, 2004). The discrepancy between the expected number of significant results and the actual number of significant results in multiple-study articles undermines the credibility of the reported results, and it is likely that questionable research practices have contributed to the reporting of too many significant results (Sterling, 1959). The problem of low power in multiple-study articles is illustrated using Bem's (2011) article on extrasensory perception and Gailliot et al.'s (2007) article on glucose and self-regulation. I conclude with several recommendations that can increase the credibility of scientific evidence in psychological journals. One major recommendation is to pay more attention to the power of studies to produce positive results without the help of questionable research practices and to request that authors justify sample sizes with a priori predictions of effect sizes. It is also important to publish replication studies with nonsignificant results if these studies have high power to replicate a published finding.}, } @article {pmid22921467, year = {2013}, author = {Marticorena-Álvarez, P and Chaparro, M and Pérez-Casas, A and Gisbert, JP}, title = {Reply to Dr. Katsanos et al.'s letter.}, journal = {Journal of Crohn's & colitis}, volume = {7}, number = {1}, pages = {e23-4}, doi = {10.1016/j.crohns.2012.07.008}, pmid = {22921467}, issn = {1876-4479}, mesh = {Anti-Inflammatory Agents/*adverse effects ; Antibodies, Monoclonal, Humanized/*adverse effects ; Crohn Disease/*drug therapy ; Female ; Humans ; Retinal Diseases/*chemically induced ; Vision Disorders/*chemically induced ; }, } @article {pmid22885035, year = {2012}, author = {Meytlis, M and Nichols, Z and Nirenberg, S}, title = {Determining the role of correlated firing in large populations of neurons using white noise and natural scene stimuli.}, journal = {Vision research}, volume = {70}, number = {}, pages = {44-53}, pmid = {22885035}, issn = {1878-5646}, support = {R01 EY007977/EY/NEI NIH HHS/United States ; R01 EY012978/EY/NEI NIH HHS/United States ; EY012978/EY/NEI NIH HHS/United States ; EY07977/EY/NEI NIH HHS/United States ; }, mesh = {Action Potentials/*physiology ; Animals ; Artifacts ; Bayes Theorem ; Macaca mulatta ; Mice ; *Models, Neurological ; Photic Stimulation/*methods ; Retina/cytology/*physiology ; Retinal Ganglion Cells/physiology ; Sensory Receptor Cells/*physiology ; Species Specificity ; Visual Cortex/cytology/*physiology ; Visual Pathways/cytology/physiology ; }, abstract = {The role of correlated firing in representing information has been a subject of much discussion. Several studies in retina, visual cortex, somatosensory cortex, and motor cortex, have suggested that it plays only a minor role, carrying <10% of the total information carried by the neurons (Gawne & Richmond, 1993; Nirenberg et al., 2001; Oram et al., 2001; Petersen, Panzeri, & Diamond, 2001; Rolls et al., 2003). A limiting factor of these studies, however, is that they were carried out using pairs of neurons; how the results extend to large populations was not clear. Recently, new methods for modeling network firing patterns have been developed (Nirenberg & Pandarinath, 2012; Pillow et al., 2008), opening the door to answering this question for more complete populations. One study, Pillow et al. (2008), showed that including correlations increased information by a modest amount, ~20%; however, this work used only a single retina (primate) and a white noise stimulus. Here we performed the analysis using several retinas (mouse) and both white noise and natural scene stimuli. The results showed that correlations added little information when white noise stimuli were used (~13%), similar to Pillow et al.'s findings, and essentially no information when natural scene stimuli were used. Further, the results showed that ignoring correlations did not change the quality of the information carried by the population (as measured by comparing the full pattern of decoding errors). These results suggest generalization: the pairwise analysis in several species show that correlations account for very little of the total information. Now, the analysis with large populations in two species show a similar result, that correlations still account for only a small fraction of the total information, and, most significantly, the amount is not statistically significant when natural stimuli are used, making rapid advances in the study of population coding possible.}, } @article {pmid22882636, year = {2012}, author = {Juujärvi, S and Myyry, L and Pesso, K}, title = {Empathy and values as predictors of care development.}, journal = {Scandinavian journal of psychology}, volume = {53}, number = {5}, pages = {413-420}, doi = {10.1111/j.1467-9450.2012.00961.x}, pmid = {22882636}, issn = {1467-9450}, mesh = {Adult ; Attitude of Health Personnel ; Caregivers/*psychology/statistics & numerical data ; *Empathy ; Female ; Finland ; Follow-Up Studies ; Health Occupations ; Humans ; *Interpersonal Relations ; Longitudinal Studies ; Male ; *Moral Development ; Social Values ; Students/psychology ; Surveys and Questionnaires ; }, abstract = {This study investigates values and affective empathy as predictors for care-based moral development. Fifty-three students from a university of applied sciences were interviewed with Skoe's Ethic of Care Interview at the beginning of their studies and two years later. Value priorities were measured by Schwartz et al.'s Portrait Value Questionnaire, empathy variables by Davis' Interpersonal Reactivity Index, and feelings of sympathy were rated using a real-life moral conflict. The results showed that students in care-oriented fields progressed in care reasoning. Real-life sympathy and the value of self-direction positively predicted development in care reasoning, whereas personal distress was a negative predictor. The results indicate that care-based moral development is more closely connected with affective empathy than personal values. Individuals who feel empathy for others, and who prefer independent thinking and action, achieve the greatest gains in care development. In conclusion, educators should encourage students' empathy and moral reasoning in authentic moral conflicts.}, } @article {pmid22882477, year = {2012}, author = {Wadey, R and Evans, L and Hanton, S and Neil, R}, title = {An examination of hardiness throughout the sport-injury process: a qualitative follow-up study.}, journal = {British journal of health psychology}, volume = {17}, number = {4}, pages = {872-893}, doi = {10.1111/j.2044-8287.2012.02084.x}, pmid = {22882477}, issn = {2044-8287}, mesh = {*Adaptation, Psychological ; Athletic Injuries/*psychology/*rehabilitation ; Emotions ; Female ; Follow-Up Studies ; Humans ; Life Change Events ; Male ; Problem Solving ; Young Adult ; }, abstract = {OBJECTIVES: This qualitative follow-up study aimed to enhance the interpretability and meaningfulness of the findings that emerged from a quantitative study that explored the effect of hardiness on the prediction of, and response to, sport injury (i.e., Wadey, Evans, Hanton, & Neil, 2012).

DESIGN: Using theory-based and maximum-variation sampling to contextualize and provide an in-depth understanding of the previous findings, the participants comprised a purposeful sample of 10 athletes from the quantitative study (M age = 21.7; SD= 1.06).

METHODS: Data were derived through semi-structured interviews, and analysed and displayed using composite sequence analysis (Miles & Huberman, 1994).

RESULTS: The findings extended Wadey et al.'s (2012) study by identifying the perceived mechanisms by which athletes high and low in hardiness exacerbated or attenuated the impact of pre-injury negative major life events (i.e., a significant predictor of sport injury) and post-injury responses. Specifically, the findings demonstrate that athletes high in hardiness possessed a refined repertoire of problem- and emotion-focused coping strategies that they used pre- and post-injury. Those athletes low in hardiness used avoidance coping strategies that had long-term negative implications.

CONCLUSIONS: These findings have important implications for the structure, timing, and content of hardiness interventions that aim to reduce rates of injury occurrence and expedite injured athletes' return to competitive sport.}, } @article {pmid22854015, year = {2013}, author = {O'Connor, DB and Walker, S and Hendrickx, H and Talbot, D and Schaefer, A}, title = {Stress-related thinking predicts the cortisol awakening response and somatic symptoms in healthy adults.}, journal = {Psychoneuroendocrinology}, volume = {38}, number = {3}, pages = {438-446}, doi = {10.1016/j.psyneuen.2012.07.004}, pmid = {22854015}, issn = {1873-3360}, support = {BB/H001476/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Adolescent ; Adult ; Female ; Humans ; Hydrocortisone/*metabolism ; Life Change Events ; Male ; Pituitary-Adrenal Function Tests/methods ; Respiratory Tract Infections/complications/*diagnosis ; Saliva/metabolism ; Stress, Psychological/complications/*metabolism/*psychology ; *Thinking ; Wakefulness ; Writing ; }, abstract = {OBJECTIVE: Perseverative cognition (i.e., worry, stress-related thinking) may prolong stress-related physiological activation. However, its role within the context of the written emotional disclosure paradigm has not been examined. This study explored: (1) the effects of stress-related thinking on the cortisol awakening response and upper respiratory infection symptoms and; (2) the efficacy of two expressive writing interventions on these health outcomes.

METHODS: Participants were randomly assigned to write about their most stressful life experience (using the Guided Disclosure Protocol; n=39) or positive life experiences (n=42) or plans for the day (n=41) for 20 min on 3 consecutive days. Participants reported the extent to which they thought about their assigned writing topic during the study and in the past (event-related thought). Cortisol was measured at 0, 15, 30 and 45 min after awakening on 2 consecutive days at baseline and 4 weeks post-intervention. Upper respiratory infection (URI) symptoms were assessed at baseline, at 4 weeks and at 6 months.

RESULTS: Results showed that the writing interventions had no beneficial effects on any of the outcome measures. However, a significant interaction was found between event-related thought and condition on the cortisol awakening response at 1 month follow-up and URI symptoms at 6 months. Among participants who wrote about stressful/traumatic events, higher stress-related thinking during the study predicted increased cortisol levels and URI symptoms compared to participants who reported low stress-related thinking.

DISCUSSION: These findings are broadly consistent with Brosschot et al.'s (2006) perseverative cognition hypothesis and highlight the importance of ruminative thinking in understanding stress-health processes.}, } @article {pmid22853838, year = {2012}, author = {Gross, BA and Tavanaiepour, D and Du, R and Al-Mefty, O and Dunn, IF}, title = {Evolution of the posterior petrosal approach.}, journal = {Neurosurgical focus}, volume = {33}, number = {2}, pages = {E7}, doi = {10.3171/2012.6.FOCUS12133}, pmid = {22853838}, issn = {1092-0684}, mesh = {History, 20th Century ; Humans ; Neurosurgical Procedures/*history ; Otolaryngology/*history ; Petrous Bone/*surgery ; }, abstract = {In this article, the authors review the history of the posterior petrosal approach. The early foundation of the retrolabyrinthine lateral petrosectomy has its roots in the otolaryngology literature. These early approaches were limited in exposure by the tentorium superiorly and the sigmoid sinus posteriorly. Although the concept of a transtentorial approach was originally combined with a complete labyrinthectomy, Hakuba and colleagues described the expansive exposure afforded by sectioning the tentorium and superior petrosal sinus and mobilizing a skeletonized sigmoid sinus. This maneuver serves as the key step in allowing for the full, combined supra- and infratentorial exposure that the posterior petrosal approach provides. In contrast to Hakuba et al.'s approach, which used a partial labyrinthectomy, modern approaches often preserve the entire labyrinth (retrolabyrinthine approach). For added exposure, the latter can be combined with the anterior petrosal approach, allowing for the preservation of hearing and an enhanced view of the surgical target. The authors review the evolution of the petrosal approach and highlight its applicability.}, } @article {pmid22848419, year = {2012}, author = {Vaesen, K}, title = {Cumulative cultural evolution and demography.}, journal = {PloS one}, volume = {7}, number = {7}, pages = {e40989}, pmid = {22848419}, issn = {1932-6203}, mesh = {*Cultural Evolution ; *Demography ; Humans ; *Models, Theoretical ; *Population Dynamics ; Tasmania ; }, abstract = {The idea that demographic change may spur or slow down technological change has become widely accepted among evolutionary archaeologists and anthropologists. Two models have been particularly influential in promoting this idea: a mathematical model by Joseph Henrich, developed to explain the Tasmanian loss of culture during the Holocene; and an agent-based adaptation thereof, devised by Powell et al. to explain the emergence of modern behaviour in the Late Pleistocene. However, the models in question make rather strong assumptions about the distribution of skills among social learners and about the selectivity of social learning strategies. Here I examine the behaviour of these models under more conservative and, on empirical and theoretical grounds, equally reasonable assumptions. I show that, some qualifications notwithstanding, Henrich's model largely withstands my robustness tests. The model of Powell et al., in contrast, does not--a finding that warrants a fair amount of skepticism towards Powell et al.'s explanation of the Upper Paleolithic transition. More generally, my evaluation of the accounts of Henrich and of Powell et al. helpfully clarify which inferences their popular models do and not support.}, } @article {pmid22843198, year = {2012}, author = {Genty, E and Karpel, H and Silberberg, A}, title = {Time preferences in long-tailed macaques (Macaca fascicularis) and humans (Homo sapiens).}, journal = {Animal cognition}, volume = {15}, number = {6}, pages = {1161-1172}, doi = {10.1007/s10071-012-0540-8}, pmid = {22843198}, issn = {1435-9456}, mesh = {Animals ; *Choice Behavior ; Feeding Behavior ; Female ; Humans ; Impulsive Behavior ; Macaca fascicularis/*psychology ; Male ; Reinforcement, Psychology ; *Time Perception ; }, abstract = {Rosati et al. (Curr Biol 17(19):1663-1668, 2007) found in a self-control test in which choice was between a smaller, immediately delivered food and a larger, delayed food, that chimpanzees preferred the larger reward (self-control); humans, however, preferred the smaller reward (impulsivity). They attributed their results to a species difference in self-control. In Experiment 1, monkeys (long-tailed macaques) were exposed to a self-control task in two conditions: where the food was hidden under differently colored bowls and where it was visible. When these two conditions were compared, choice shifted from greater preference for the impulsive alternative in the hidden condition to greater preference for the self-control alternative in the visible condition. Additionally, in both conditions, preference shifted from self-control to impulsivity over sessions. These results were explained in terms of the reversed-contingency effect (a propensity to reach for more over less when rewards are visible) and not to a capacity for self-control. In Experiment 2, humans that demonstrated preference for more over less in choice preferred the impulsive alternative when choice to either alternative was followed by the same intertrial interval-a preference that accelerates trial rates relative to preference of the self-control alternative. When trial rates were equated so that neither choice accelerated session's end, humans demonstrated self-control. These results suggest that Rosati et al.'s demonstration of impulsivity in humans was due to participants' desire to minimize session time.}, } @article {pmid22834757, year = {2012}, author = {Hardy, OJ and Pavoine, S}, title = {Assessing phylogenetic signal with measurement error: a comparison of Mantel tests, Blomberg et al.'s K, and phylogenetic distograms.}, journal = {Evolution; international journal of organic evolution}, volume = {66}, number = {8}, pages = {2614-2621}, doi = {10.1111/j.1558-5646.2012.01623.x}, pmid = {22834757}, issn = {1558-5646}, mesh = {*Biological Evolution ; *Data Interpretation, Statistical ; Models, Genetic ; *Phylogeny ; Research Design ; }, abstract = {In macroevolutionary studies, different approaches are commonly used to measure phylogenetic signal--the tendency of related taxa to resemble one another--including the K statistic and the Mantel test. The latter was recently criticized for lacking statistical power. Using new simulations, we show that the power of the Mantel test depends on the metrics used to define trait distances and phylogenetic distances between species. Increasing power is obtained by lowering variance and increasing negative skewness in interspecific distances, as obtained using Euclidean trait distances and the complement of Abouheif proximity as a phylogenetic distance. We show realistic situations involving "measurement error" due to intraspecific variability where the Mantel test is more powerful to detect a phylogenetic signal than a permutation test based on the K statistic. We highlight limitations of the K-statistic (univariate measure) and show that its application should take into account measurement errors using repeated measures per species to avoid estimation bias. Finally, we argue that phylogenetic distograms representing Euclidean trait distance as a function of the square root of patristic distance provide an insightful representation of the phylogenetic signal that can be used to assess both the impact of measurement error and the departure from a Brownian evolution model.}, } @article {pmid22827073, year = {2012}, author = {Qu, Y and Liu, SH and Li, XW}, title = {[A novel method for extracting leaf-level solar-induced fluorescence of typical crops under Cu stress].}, journal = {Guang pu xue yu guang pu fen xi = Guang pu}, volume = {32}, number = {5}, pages = {1282-1286}, pmid = {22827073}, issn = {1000-0593}, mesh = {Brassica ; Chlorophyll/analysis ; Copper/*toxicity ; Crops, Agricultural/*chemistry ; *Fluorescence ; Pisum sativum ; *Plant Leaves ; Spectrometry, Fluorescence ; Triticum ; }, abstract = {The leaf-level solar-induced fluorescence changes when the typical crops are under Cu stress, which can be considered as a sensitive indicator to estimate the stress level. In the present study, wheat (Triticum aestivum L.), pea (Pisum sativum L.) and Chinese cabbage (Brassica campestris L.) were selected and cultured with copper solutions or copper polluted soil with different Cu stress. The apparent reflectance of leaves was measured by an ASD Fieldspec spectrometer and an integrating sphere. As the apparent reflectance was seldom affected by the fluorescence emission at 580-650 and 800-1000 nm, so the apparent solar-induced fluorescence can be separated from the apparent reflectance based on PROSPECT model. The re-absorption effect of chlorophyll was corrected by three methods, called GM (Gitelson et al.'s model), AM (Agati et al.'s model) and LM (Lagorio et al.'s model). After the re-absorption correction, the solar-induced fluorescence under different Cu stress was obtained, and a positive relationship was found between the height of far RED fluorescence (FRF) and the copper contents in leaves.}, } @article {pmid22823233, year = {2012}, author = {Lynam, DR and Miller, JD}, title = {Fearless dominance and psychopathy: a response to Lilienfeld et al.}, journal = {Personality disorders}, volume = {3}, number = {3}, pages = {341-353}, doi = {10.1037/a0028296}, pmid = {22823233}, issn = {1949-2723}, mesh = {Antisocial Personality Disorder/*diagnosis ; Disruptive, Impulse Control, and Conduct Disorders/*psychology ; *Fear ; *Personality Inventory ; *Social Dominance ; }, abstract = {We respond to criticisms raised by Lilienfeld et al. (2012, The role of fearless dominance in psychopathy: Confusions, controversies, and clarifications. Personality Disorders: Theory, Research, and Treatment, 3, 327-340) about our meta-analysis (Miller & Lynam, 2012, An examination of the Psychopathic Personality Inventory's nomological network: A meta-analytic review. Personality Disorders: Theory, Research, and Treatment, 3, 305-326). We argue that Lilienfeld et al. commit multiple logical and scientific errors throughout their response: minimizing the centrality of antisocial behavior in previous conceptions of psychopathy, magnifying the role of psychological health in these same conceptions, ignoring the relative sizes of relations, and selective reporting of studies and specific findings within studies. We identify two points of agreement with Lilienfeld et al.: (a) the presence of fearless dominance (FD) traits is not sufficient to indicate the presence of psychopathy; and (b) traits related to FD may have a role to play in psychopathy. Beyond these points of agreement, we find Lilienfeld et al.'s response to be less than compelling. We reiterate our main conclusions that Psychopathic Personality Inventory's FD subscale assesses stable extraversion and is, at best, considered a diagnostic specifier rather than an essential feature.}, } @article {pmid22809493, year = {2012}, author = {Kakde, S and Bhopal, RS and Jones, CM}, title = {A systematic review on the social context of smokeless tobacco use in the South Asian population: implications for public health.}, journal = {Public health}, volume = {126}, number = {8}, pages = {635-645}, doi = {10.1016/j.puhe.2012.05.002}, pmid = {22809493}, issn = {1476-5616}, mesh = {Asia, Southeastern/epidemiology/ethnology ; Asian People/psychology ; Cultural Characteristics ; Health Knowledge, Attitudes, Practice ; Humans ; Meta-Analysis as Topic ; *Social Conditions ; *Tobacco, Smokeless/adverse effects ; United Kingdom/epidemiology ; }, abstract = {OBJECTIVES: Smokeless tobacco (SLT) is an addiction resulting in serious health problems including cancers. The social context around SLT use among South Asians was reviewed to help inform interventions for its prevention and cessation.

STUDY DESIGN: Systematic review.

METHODS: Electronic databases were searched to identify studies examining the social context of SLT use. As heterogeneous qualitative, quantitative and mixed method studies were included, meta-analysis was not appropriate.

RESULTS: Of 428 studies identified, 17 were reviewed. These studies were conducted in India, Nepal, Pakistan and the UK between 1994 and 2009. SLT use among South Asians was culturally widely acceptable due to its association with socializing, sharing and family tradition (100% in Anwar et al.'s study). Other reasons for use were addiction, easy accessibility, low cost and lack of prohibitive legislation. SLT users had limited awareness of its association with oral cancer (29.3% in Ahmed et al.'s study); however, there was a distinct lack of knowledge regarding other health effects, such as cardiovascular disease (0.85%). Users attempted to quit (32.7% in Prabhu et al.'s study) but success was low (8.2%).

CONCLUSIONS: Cessation programmes for South Asians should address cultural acceptance, limited knowledge of health effects, inadequate legislation and controls, scarce social support and insufficient SLT cessation services.}, } @article {pmid22790484, year = {2012}, author = {Hilton, JM and Gonzalez, CA and Saleh, M and Maitoza, R and Anngela-Cole, L}, title = {Perceptions of successful aging among older Latinos, in cross-cultural context.}, journal = {Journal of cross-cultural gerontology}, volume = {27}, number = {3}, pages = {183-199}, pmid = {22790484}, issn = {1573-0719}, mesh = {Activities of Daily Living/psychology ; Aged ; Aged, 80 and over ; Aging/*ethnology/*psychology ; Attitude to Health/*ethnology ; *Cross-Cultural Comparison ; Family/ethnology ; Female ; Hispanic or Latino/*psychology ; Humans ; Interviews as Topic ; Leisure Activities/psychology ; Male ; Middle Aged ; Personal Satisfaction ; Qualitative Research ; Quality of Life/psychology ; Social Support ; Socioeconomic Factors ; Spirituality ; Surveys and Questionnaires ; }, abstract = {Latinos are the largest and fastest growing minority group in the U.S. but they have been overlooked in studies of successful aging. This study used a multi-method approach with an open-ended question and Phelan et al.'s (Journal of American Geriatrics Society 52:211-216, 2004) Successful Aging Measure to determine whether the quantitative measure fully captured perceptions of successful aging of 60 older Latinos living in three Western states. Then, the findings were compared with other studies that had used the measure with Anglo, Japanese, Japanese-American, and Latin American samples. The results revealed that Latinos and Latin Americans responses are very similar to each other, and somewhat different from other cultural groups. Latinos focus on maintaining a positive outlook, living in the present, enjoying a sense of community, and relying on spirituality and family for comfort and meaning as they age, but they also worry about finances. There are several components of this study that professionals can use to guide their practice, including a summary of methodological challenges and ongoing conceptual debates in the successful aging literature.}, } @article {pmid22760677, year = {2012}, author = {Ahnis, A and Holzhausen, M and Rockwood, TH and Rosemeier, HP}, title = {FLQAI - A Questionnaire on Quality of Life in Fecal Incontinence: German translation and validation of Rockwood et al.'s (2000) Fecal Incontinence Quality of Life Scale (FIQLS).}, journal = {Zeitschrift fur Gastroenterologie}, volume = {50}, number = {7}, pages = {661-669}, doi = {10.1055/s-0031-1299318}, pmid = {22760677}, issn = {1439-7803}, mesh = {Aged ; Fecal Incontinence/*diagnosis/*epidemiology/psychology ; Female ; Germany/epidemiology ; Humans ; Male ; Prevalence ; *Quality of Life ; Reproducibility of Results ; Sensitivity and Specificity ; *Severity of Illness Index ; *Surveys and Questionnaires ; Urinary Incontinence/*diagnosis/*epidemiology/psychology ; }, abstract = {AIM: The aim of the study was to produce a German version (FLQAI) of the Fecal Incontinence Quality of Life Scale (FIQLS) by Rockwood et al., an English-language measure of quality of life in fecal incontinence 1. The FIQLS has 29 items assigned to the four subscales of lifestyle, coping/behavior, depression/self-perception and embarrassment.

MATERIAL AND METHODS: The FIQLS 1 was translated into German and adapted. Indicators of test quality (convergent and discriminant validity, reliability, confirmatory factor analysis) were determined in N = 88 subjects (mean age = 71.5 years) with fecal incontinence and urinary incontinence (control group, n = 29).

RESULTS: Three of the four scales of the FLQAI had an acceptable internal reliability. The scales of the FLQAI showed significant correlations with selected subscales of the SF-36 2, the ADS 3 and the FISI 4 (convergent validity). Two of the four scales of the FLQAI discriminated between patients with fecal incontinence and patients with urinary incontinence (discriminant validity). The confirmatory factor analysis did not reveal a uniform fit of the data obtained with the German version with the original four-factor solution of the original version of the questionnaire.

DISCUSSION: The Questionnaire on Quality of Life in Fecal Incontinence (FLQAI) is a German-language self-rating questionnaire with satisfactory psychometric properties for measuring disease-specific quality of life in elderly patients with fecal incontinence.}, } @article {pmid22759451, year = {2012}, author = {Cook, JM and O'Donnell, C and Dinnen, S and Coyne, JC and Ruzek, JI and Schnurr, PP}, title = {Measurement of a model of implementation for health care: toward a testable theory.}, journal = {Implementation science : IS}, volume = {7}, number = {}, pages = {59}, pmid = {22759451}, issn = {1748-5908}, support = {K01 MH070859/MH/NIMH NIH HHS/United States ; R25 MH080916/MH/NIMH NIH HHS/United States ; RC1 MH088454/MH/NIMH NIH HHS/United States ; }, mesh = {Communication ; Health Services Research/*methods ; Humans ; Information Dissemination/methods ; Interviews as Topic ; Leadership ; Organizational Innovation ; Surveys and Questionnaires ; Translational Research, Biomedical/*methods ; }, abstract = {BACKGROUND: Greenhalgh et al. used a considerable evidence-base to develop a comprehensive model of implementation of innovations in healthcare organizations [1]. However, these authors did not fully operationalize their model, making it difficult to test formally. The present paper represents a first step in operationalizing Greenhalgh et al.'s model by providing background, rationale, working definitions, and measurement of key constructs.

METHODS: A systematic review of the literature was conducted for key words representing 53 separate sub-constructs from six of the model's broad constructs. Using an iterative process, we reviewed existing measures and utilized or adapted items. Where no one measure was deemed appropriate, we developed other items to measure the constructs through consensus.

RESULTS: The review and iterative process of team consensus identified three types of data that can been used to operationalize the constructs in the model: survey items, interview questions, and administrative data. Specific examples of each of these are reported.

CONCLUSION: Despite limitations, the mixed-methods approach to measurement using the survey, interview measure, and administrative data can facilitate research on implementation by providing investigators with a measurement tool that captures most of the constructs identified by the Greenhalgh model. These measures are currently being used to collect data concerning the implementation of two evidence-based psychotherapies disseminated nationally within Department of Veterans Affairs. Testing of psychometric properties and subsequent refinement should enhance the utility of the measures.}, } @article {pmid22748099, year = {2012}, author = {Chen, ZZ and Wang, L and Yamanaka, S}, title = {A fast tool for minimum hybridization networks.}, journal = {BMC bioinformatics}, volume = {13}, number = {}, pages = {155}, pmid = {22748099}, issn = {1471-2105}, mesh = {*Algorithms ; Computational Biology/methods ; Computer Simulation ; *Hybridization, Genetic ; *Phylogeny ; Poaceae/genetics ; *Software ; }, abstract = {BACKGROUND: Due to hybridization events in evolution, studying two different genes of a set of species may yield two related but different phylogenetic trees for the set of species. In this case, we want to combine the two phylogenetic trees into a hybridization network with the fewest hybridization events. This leads to three computational problems, namely, the problem of computing the minimum size of a hybridization network, the problem of constructing one minimum hybridization network, and the problem of enumerating a representative set of minimum hybridization networks. The previously best software tools for these problems (namely, Chen and Wang's HybridNet and Albrecht et al.'s Dendroscope 3) run very slowly for large instances that cannot be reduced to relatively small instances. Indeed, when the minimum size of a hybridization network of two given trees is larger than 23 and the problem for the trees cannot be reduced to relatively smaller independent subproblems, then HybridNet almost always takes longer than 1 day and Dendroscope 3 often fails to complete. Thus, a faster software tool for the problems is in need.

RESULTS: We develop a software tool in ANSI C, named FastHN, for the following problems: Computing the minimum size of a hybridization network, constructing one minimum hybridization network, and enumerating a representative set of minimum hybridization networks. We obtain FastHN by refining HybridNet with three ideas. The first idea is to preprocess the input trees so that the trees become smaller or the problem becomes to solve two or more relatively smaller independent subproblems. The second idea is to use a fast algorithm for computing the rSPR distance of two given phylognetic trees to cut more branches of the search tree in the exhaustive-search stage of the algorithm. The third idea is that during the exhaustive-search stage of the algorithm, we find two sibling leaves in one of the two forests (obtained from the given trees by cutting some edges) such that they are as far as possible in the other forest. As the result, FastHN always runs much faster than HybridNet. Unlike Dendroscope 3, FastHN is a single-threaded program. Despite this disadvantage, our experimental data shows that FastHN runs substantially faster than the multi-threaded Dendroscope 3 on a PC with multiple cores. Indeed, FastHN can finish within 16 minutes (on average on a Windows-7 (x64) desktop PC with i7-2600 CPU) even if the minimum size of a hybridization network of two given trees is about 25, the trees each have 100 leaves, and the problem for the input trees cannot be reduced to two or more independent subproblems via cluster reductions. It is also worth mentioning that like HybridNet, FastHN does not use much memory (indeed, the amount of memory is at most quadratic in the input size). In contrast, Dendroscope 3 uses a huge amount of memory. Executables of FastHN for Windows XP (x86), Windows 7 (x64), Linux, and Mac OS are available (see the Results and discussion section for details).

CONCLUSIONS: For both biological datasets and simulated datasets, our experimental results show that FastHN runs substantially faster than HybridNet and Dendroscope 3. The superiority of FastHN in speed over the previous tools becomes more significant as the hybridization number becomes larger. In addition, FastHN uses much less memory than Dendroscope 3 and uses the same amount of memory as HybridNet.}, } @article {pmid22727633, year = {2012}, author = {Xiao, L and Yank, V and Ma, J}, title = {Algorithm for balancing both continuous and categorical covariates in randomized controlled trials.}, journal = {Computer methods and programs in biomedicine}, volume = {108}, number = {3}, pages = {1185-1190}, doi = {10.1016/j.cmpb.2012.06.001}, pmid = {22727633}, issn = {1872-7565}, support = {R34 DK080878/DK/NIDDK NIH HHS/United States ; R34DK080878/DK/NIDDK NIH HHS/United States ; }, mesh = {*Algorithms ; Humans ; Probability ; *Randomized Controlled Trials as Topic ; }, abstract = {Minimization as proposed by Pocock and Simon for balancing categorical covariates in clinical trials with individual-level, consecutive randomization has been increasingly used. An extension of the method exists that uses the symmetric Kullback-Leibler divergence index to balance both categorical and continuous covariates, albeit for two-arm randomized controlled trials only. To date, the algorithm has not been made widely available to researchers via publicly accessible software. We adapted Endo et al.'s algorithm to randomized trials with two or more arms. In addition, our algorithm incorporates Efron's biased coin method to decrease the predictability of assignment even when a predefined threshold of difference in the numbers of subjects between treatment arms is reached, whereas Endo et al.'s algorithm assigns the next subject to the treatment of smaller size with certainty. We developed code in the free statistical software R to make the algorithm readily available to trialists. While there are no definitive answers regarding the optimal choices for certain statistical parameters that must be defined prior to algorithm application (P(k), D(n), and p_D(n)), we provide guidance on these. We conducted simulations with actual data from a three-arm randomized trial to compare the modified algorithm and R code to another published biased coin minimization method that can accommodate continuous and categorical covariates in multi-arm trials. The three-arm trial used three categorical covariates (sex, race/ethnicity, and online personal health record access) and four continuous covariates (age, fasting blood glucose, body mass index, and waist circumference). All of the continuous and categorical covariates were well balanced, and the results were comparable to the comparison method.}, } @article {pmid22726412, year = {2012}, author = {Besche-Richard, C and Bourrin-Tisseron, A and Olivier, M and Cuervo-Lombard, CV and Limosin, F}, title = {[Recognition of facial emotions and theory of mind in schizophrenia: could the theory of mind deficit be due to the non-recognition of facial emotions?].}, journal = {L'Encephale}, volume = {38}, number = {3}, pages = {241-247}, doi = {10.1016/j.encep.2011.04.006}, pmid = {22726412}, issn = {0013-7006}, mesh = {Adult ; Cognition Disorders/diagnosis/psychology ; Comprehension ; *Culture ; *Emotions ; Executive Function ; *Facial Expression ; Female ; France ; Humans ; *Interpersonal Relations ; Male ; Memory, Short-Term ; Middle Aged ; Neuropsychological Tests/statistics & numerical data ; *Pattern Recognition, Visual ; Psychometrics ; *Recognition, Psychology ; Reference Values ; Schizophrenia/*diagnosis ; *Schizophrenic Psychology ; *Theory of Mind ; }, abstract = {OBJECTIVES: The deficits of recognition of facial emotions and attribution of mental states are now well-documented in schizophrenic patients. However, we don't clearly know about the link between these two complex cognitive functions, especially in schizophrenia. In this study, we attempted to test the link between the recognition of facial emotions and the capacities of mentalization, notably the attribution of beliefs, in health and schizophrenic participants. We supposed that the level of performance of recognition of facial emotions, compared to the working memory and executive functioning, was the best predictor of the capacities to attribute a belief.

METHODS: Twenty schizophrenic participants according to DSM-IVTR (mean age: 35.9 years, S.D. 9.07; mean education level: 11.15 years, S.D. 2.58) clinically stabilized, receiving neuroleptic or antipsychotic medication participated in the study. They were matched on age (mean age: 36.3 years, S.D. 10.9) and educational level (mean educational level: 12.10, S.D. 2.25) with 30 matched healthy participants. All the participants were evaluated with a pool of tasks testing the recognition of facial emotions (the faces of Baron-Cohen), the attribution of beliefs (two stories of first order and two stories of second order), the working memory (the digit span of the WAIS-III and the Corsi test) and the executive functioning (Trail Making Test A et B, Wisconsin Card Sorting Test brief version).

RESULTS: Comparing schizophrenic and healthy participants, our results confirmed a difference between the performances of the recognition of facial emotions and those of the attribution of beliefs. The result of the simple linear regression showed that the recognition of facial emotions, compared to the performances of working memory and executive functioning, was the best predictor of the performances in the theory of mind stories.

DISCUSSION: Our results confirmed, in a sample of schizophrenic patients, the deficits in the recognition of facial emotions and in the attribution of mental states. Our new result concerned the demonstration that the performances in the recognition of facial emotions are the best predictor of the performances in the attribution of beliefs. With Marshall et al.'s model on empathy, we can explain this link between the recognition of facial emotions and the comprehension of beliefs.}, } @article {pmid22723776, year = {2012}, author = {Auvray, M and Rohde, M}, title = {Perceptual crossing: the simplest online paradigm.}, journal = {Frontiers in human neuroscience}, volume = {6}, number = {}, pages = {181}, pmid = {22723776}, issn = {1662-5161}, abstract = {Researchers in social cognition increasingly realize that many phenomena cannot be understood by investigating offline situations only, focusing on individual mechanisms and an observer perspective. There are processes of dynamic emergence specific to online situations, when two or more persons are engaged in a real-time interaction that are more than just the sum of the individual capacities or behaviors, and these require the study of online social interaction. Auvray et al.'s (2009) perceptual crossing paradigm offers possibly the simplest paradigm for studying such online interactions: two persons, a one-dimensional space, one bit of information, and a yes/no answer. This study has provoked a lot of resonance in different areas of research, including experimental psychology, computer/robot modeling, philosophy, psychopathology, and even in the field of design. In this article, we review and critically assess this body of literature. We give an overview of both behavioral experimental research and simulated agent modeling done using the perceptual crossing paradigm. We discuss different contexts in which work on perceptual crossing has been cited. This includes the controversy about the possible constitutive role of perceptual crossing for social cognition. We conclude with an outlook on future research possibilities, in particular those that could elucidate the link between online interaction dynamics and individual social cognition.}, } @article {pmid22723014, year = {2012}, author = {Zaal, FT and Bongers, RM and Pepping, GJ and Bootsma, RJ}, title = {Base on balls for the Chapman strategy: reassessing Brouwer, Brenner, and Smeets (2002).}, journal = {Attention, perception & psychophysics}, volume = {74}, number = {7}, pages = {1488-1498}, pmid = {22723014}, issn = {1943-393X}, mesh = {Humans ; *Motion Perception ; *Visual Perception ; }, abstract = {A true understanding of skilled behavior includes the identification of the information that underlies the perception-action cycle at work. Often, observers' sensitivity to perceptual variables is established in laboratory-situated simulation-based psychophysical experiments. The observers' sensitivity thus determined is then used to draw conclusions that will generalize the findings to natural behavior. Focusing on the example of running to catch fly balls, the present contribution takes the study of Brouwer, Brenner, and Smeets (Perception & Psychophysics 64:1160-1168, 2002) to illustrate how common assumptions in the steps from psychophysical experiments to natural behavior can result in ungrounded conclusions. These authors built an argument to reject the use of the Chapman strategy of zeroing out optical acceleration. For this argument, they determined the sensitivity of the visual system to acceleration, assuming that acceleration is detected as a velocity ratio. Next, they showed that catchers started running earlier than could be expected on the basis of sensitivity thresholds for this velocity ratio, concluding that running initiation could not have been based on optical acceleration. In the present study, we argue that important assumptions in the Brouwer et al. (Perception & Psychophysics 64:1160-1168, 2002) line of argument are incorrect. First, we show how the assumption of parabolic ball flight trajectories, although convenient, biased Brouwer et al.'s (Perception & Psychophysics 64:1160-1168, 2002) conclusion. Next, we present an experiment revealing that observers do not base their judgments of acceleration on the velocity ratio. Thus, we demonstrate that Brouwer et al.'s (Perception & Psychophysics 64:1160-1168, 2002) argument that optical acceleration cannot serve as the information for running to catch fly balls does not hold.}, } @article {pmid22722957, year = {2013}, author = {Snyder, JK and Fessler, DM}, title = {Reexamining individual differences in women's rape avoidance behaviors.}, journal = {Archives of sexual behavior}, volume = {42}, number = {4}, pages = {543-551}, doi = {10.1007/s10508-012-9987-6}, pmid = {22722957}, issn = {1573-2800}, mesh = {*Adaptation, Psychological ; Adolescent ; Adult ; Aged ; Female ; Humans ; *Individuality ; Middle Aged ; Rape/*prevention & control/psychology ; Sexual Harassment/*prevention & control/psychology ; Surveys and Questionnaires ; Women/*psychology ; }, abstract = {A growing number of investigators explore evolutionary psychological hypotheses concerning the avoidance of rape using self-report measures of behavior. Among the most recent and most ambitious, is the work of McKibbin et al. (2011). McKibbin et al. presented evidence supporting their predictions that such behaviors would vary according to the individual's physical attractiveness, relationship status, and proximity to kin. In addition, McKibbin et al. predicted, but failed to find evidence, that age would exercise a similar influence. We question McKibbin et al.'s position on both theoretical and empirical grounds, arguing that (1) two of their predictions do not rule out alternative explanations, and (2) their key supporting findings may well be artifacts of their measurement instrument, the Rape Avoidance Inventory (RAI). Employing new empirical evidence derived from a broader sample of U.S. women, we simultaneously tested McKibbin et al.'s predictions and compared the RAI to alternative dependent measures. We found that McKibbin et al.'s substantive predictions were not supported, and suggest that there may be limits to the utility of the RAI beyond one specific demographic category.}, } @article {pmid22696844, year = {2012}, author = {Bai, X and Chan, KS and Chow, N}, title = {Validation of Self-Image of Aging Scale for Chinese elders.}, journal = {International journal of aging & human development}, volume = {74}, number = {1}, pages = {67-86}, doi = {10.2190/AG.74.1.d}, pmid = {22696844}, issn = {0091-4150}, mesh = {Aged ; Aged, 80 and over ; Aging/*psychology ; Asian People/*psychology ; *Body Image ; China ; Female ; Humans ; Male ; Middle Aged ; Psychometrics/standards ; Reproducibility of Results ; *Self Concept ; Surveys and Questionnaires/*standards ; }, abstract = {Researchers are increasingly interested in the "image of aging" concept. Models on the image of aging abound, but few have rigorously tested measures that are culturally sensitive and domain-specific. This study first translates Levy et al.'s (2004) Image of Aging Scale into the Chinese language and revises it into the Chinese Version of the Self-Image of Aging Scale (SIAS-C). Based on the results of a survey of 445 elderly people in Wuhan-China, it then reports the factorial structure of SIAS-C and some of its psychometric properties. Confirmatory factor analysis (CFA) supports a conceptually meaningful five-factor model, as suggested in an exploratory factor analysis (EFA). The 14-item SIAS-C vindicates an acceptable level of internal consistency and test-retest reliability. Its criteria-referenced validity is demonstrated by its correlation with several criteria in expected directions. In conclusion, the SIAS-C is a psychometrically sound instrument which is recommended for use among Chinese older people.}, } @article {pmid22686555, year = {2012}, author = {Quinn, F and Johnston, M and Dixon, D and Johnston, DW and Pollard, B and Rowley, DI}, title = {Testing the integration of ICF and behavioral models of disability in orthopedic patients: replication and extension.}, journal = {Rehabilitation psychology}, volume = {57}, number = {2}, pages = {167-177}, doi = {10.1037/a0028083}, pmid = {22686555}, issn = {1939-1544}, mesh = {Activities of Daily Living/classification/psychology ; Adult ; Aged ; Aged, 80 and over ; Arthritis, Rheumatoid/*psychology/*surgery ; Arthroplasty, Replacement, Hip/*psychology ; Arthroplasty, Replacement, Knee/*psychology/*rehabilitation ; *Disability Evaluation ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; *Models, Psychological ; Osteoarthritis/*psychology/*surgery ; Pain Measurement ; Psychometrics/statistics & numerical data ; Reproducibility of Results ; *Sick Role ; Surveys and Questionnaires ; }, abstract = {OBJECTIVE: Disability from chronic illness is a major problem for society, yet the study of its determinants lacks an overall theoretical paradigm. Johnston (1996) has proposed conceptualizing disability as behavior and integrating biomedical and behavioral predictors. Dixon, Johnston, Rowley, and Pollard (2008) tested a model including constructs from the International Classification of Functioning, Disability and Health (ICF) and the theory of planned behavior (TPB) using structural equation modeling; it fitted better and explained more variance than the ICF or TPB alone. We replicated their study with a new sample from the same population (orthopedic patients awaiting joint replacement) and also tested the model after the patients had surgery.

METHODS: Two weeks before surgery, 342 orthopedic patients who had joint pain (most with arthritis) completed a questionnaire, with 228 completing it again 1 year after surgery. The authors tested Dixon et al.'s best-fit models cross-sectionally (before and after surgery) and assessed the goodness of fit of these imposed models to our data using structural equation modeling.

RESULTS: Findings strongly supported those of Dixon et al. Before surgery, results were very similar to Dixon et al. with all models accounting for significant variance and fitting well, but the integrated model fitted better and accounted for more variance. One year after surgery, Dixon et al.'s models showed even stronger fit to the data.

CONCLUSIONS: Although behavioral and biomedical (ICF) models were supported, the integrated model provided a better explanation of disability in this population than either of these models alone and suggests biopsychosocial interventions to reduce disability.}, } @article {pmid22686161, year = {2012}, author = {Heathcote, A and Hayes, B}, title = {Diffusion versus linear ballistic accumulation: different models for response time with different conclusions about psychological mechanisms?.}, journal = {Canadian journal of experimental psychology = Revue canadienne de psychologie experimentale}, volume = {66}, number = {2}, pages = {125-136}, doi = {10.1037/a0028189}, pmid = {22686161}, issn = {1878-7290}, mesh = {*Choice Behavior ; Humans ; *Models, Psychological ; *Practice, Psychological ; *Reaction Time ; }, abstract = {Two similar classes of evidence-accumulation model have dominated theorizing about rapid binary choice: diffusion models and racing accumulator pairs. Donkin, Brown, Heathcote, and Wagenmakers (2011) examined mimicry between the Ratcliff diffusion (RD; Ratcliff & Smith, 2004) and the linear ballistic accumulator (LBA; Brown & Heathcote, 2008), the 2 least similar models from each class that provide a comprehensive account of a set benchmark phenomena in rapid binary choice. Where conditions differed only in the rate of evidence accumulation (the most common case in past research), simulations showed the models supported equivalent psychological inferences. In contrast, differences in 2 other parameters of key psychological interest, response caution (the amount of information required for a decision), and nondecision time, traded-off when fitting 1 model to data simulated from the other, implying the potential for divergent inferences about latent cognitive processes. However, Donkin, Brown, Heathcote, and Wagenmakers did not find such inconsistencies between fits of the RD and LBA models in a survey of data sets from paradigms using a range of experimental manipulations. We examined a further data set, collected by Dutilh, Vandekerckhove, Tuerlinckx, and Wagenmakers (2009), which used a manipulation not surveyed by Donkin, Brown, Heathcote, and Wagenmakers's practice. Dutilh et al.'s RD model fits indicated that practice had large effects on all three types of parameters. We show that in this case the LBA provides a different and simpler account of practice effects. Implications for evidence accumulation modelling are discussed.}, } @article {pmid22680545, year = {2012}, author = {Leövey, AE and Lux, T}, title = {Parameter estimation and forecasting for multiplicative log-normal cascades.}, journal = {Physical review. E, Statistical, nonlinear, and soft matter physics}, volume = {85}, number = {4 Pt 2}, pages = {046114}, doi = {10.1103/PhysRevE.85.046114}, pmid = {22680545}, issn = {1550-2376}, mesh = {Algorithms ; Biophysics/*methods ; Commerce ; Forecasting ; Humans ; Markov Chains ; Models, Statistical ; Monte Carlo Method ; Nonlinear Dynamics ; Normal Distribution ; Numerical Analysis, Computer-Assisted ; Physics/methods ; Probability ; Stochastic Processes ; Time Factors ; }, abstract = {We study the well-known multiplicative log-normal cascade process in which the multiplication of Gaussian and log normally distributed random variables yields time series with intermittent bursts of activity. Due to the nonstationarity of this process and the combinatorial nature of such a formalism, its parameters have been estimated mostly by fitting the numerical approximation of the associated non-Gaussian probability density function to empirical data, cf. Castaing et al. [Physica D 46, 177 (1990)]. More recently, alternative estimators based upon various moments have been proposed by Beck [Physica D 193, 195 (2004)] and Kiyono et al. [Phys. Rev. E 76, 041113 (2007)]. In this paper, we pursue this moment-based approach further and develop a more rigorous generalized method of moments (GMM) estimation procedure to cope with the documented difficulties of previous methodologies. We show that even under uncertainty about the actual number of cascade steps, our methodology yields very reliable results for the estimated intermittency parameter. Employing the Levinson-Durbin algorithm for best linear forecasts, we also show that estimated parameters can be used for forecasting the evolution of the turbulent flow. We compare forecasting results from the GMM and Kiyono et al.'s procedure via Monte Carlo simulations. We finally test the applicability of our approach by estimating the intermittency parameter and forecasting of volatility for a sample of financial data from stock and foreign exchange markets.}, } @article {pmid22673892, year = {2012}, author = {Chen, HM and Lo, JW and Yeh, CK}, title = {An efficient and secure dynamic ID-based authentication scheme for telecare medical information systems.}, journal = {Journal of medical systems}, volume = {36}, number = {6}, pages = {3907-3915}, pmid = {22673892}, issn = {0148-5598}, mesh = {*Access to Information ; Computer Security/*instrumentation ; Confidentiality ; Home Care Services ; *Medical Informatics ; Telecommunications ; *Telemedicine ; User-Computer Interface ; }, abstract = {The rapidly increased availability of always-on broadband telecommunication environments and lower-cost vital signs monitoring devices bring the advantages of telemedicine directly into the patient's home. Hence, the control of access to remote medical servers' resources has become a crucial challenge. A secure authentication scheme between the medical server and remote users is therefore needed to safeguard data integrity, confidentiality and to ensure availability. Recently, many authentication schemes that use low-cost mobile devices have been proposed to meet these requirements. In contrast to previous schemes, Khan et al. proposed a dynamic ID-based remote user authentication scheme that reduces computational complexity and includes features such as a provision for the revocation of lost or stolen smart cards and a time expiry check for the authentication process. However, Khan et al.'s scheme has some security drawbacks. To remedy theses, this study proposes an enhanced authentication scheme that overcomes the weaknesses inherent in Khan et al.'s scheme and demonstrated this scheme is more secure and robust for use in a telecare medical information system.}, } @article {pmid22654598, year = {2012}, author = {Noor, Z and Sumitro, SB and Hidayat, M and Rahim, AH and Sabarudin, A and Umemura, T}, title = {Atomic mineral characteristics of Indonesian osteoporosis by high-resolution inductively coupled plasma mass spectrometry.}, journal = {TheScientificWorldJournal}, volume = {2012}, number = {}, pages = {372972}, pmid = {22654598}, issn = {1537-744X}, mesh = {Female ; Humans ; Mass Spectrometry/*methods ; Minerals/*analysis/metabolism ; Osteoporosis/*metabolism ; Osteoporosis, Postmenopausal/metabolism ; }, abstract = {Clinical research indicates that negative calcium balance is associated with low bone mass, rapid bone loss, and high fracture rates. However, some studies revealed that not only calcium is involved in bone strengthening as risk factor of fracture osteoporosis. Thus, in this report, the difference of metallic and nonmetallic elements in osteoporosis and normal bones was studied by high-resolution inductively coupled plasma mass spectrometry (HR-ICP-MS). The influence of these elements on bone metabolic processes is also discussed. Inclusion criteria of bone samples consist of postmenopausal woman, trabecular bone fracture, normal and osteoporosis BMD value, and no history of previous disease. The results showed that the concentration of B, Al, S, V, Co, Mo, Te, Ba, La, Ni, As, and Ca/P ratio is higher in osteoporosis than normal. These atomic minerals have negative role to imbalance between bone resorption and bone formation activity. Conversely, concentrations of Na, Mg, P, K, Ca, Cr, Pd, Ag, Mn, Fe, Cu, Zn, Rb, Sr, Pb, and Se are lower in osteoporosis than in normal bones. Among these atoms, known to have important roles in bone structure, we found involvement of atomic mineral and calcium which are considerable to contribute to osteoporotic phenomena.}, } @article {pmid22654177, year = {2011}, author = {Doloc-Mihu, A and Calabrese, RL}, title = {A database of computational models of a half-center oscillator for analyzing how neuronal parameters influence network activity.}, journal = {Journal of biological physics}, volume = {37}, number = {3}, pages = {263-283}, pmid = {22654177}, issn = {1573-0689}, support = {R01 NS024072/NS/NINDS NIH HHS/United States ; R56 NS024072/NS/NINDS NIH HHS/United States ; }, abstract = {A half-center oscillator (HCO) is a common circuit building block of central pattern generator networks that produce rhythmic motor patterns in animals. Here we constructed an efficient relational database table with the resulting characteristics of the Hill et al.'s (J Comput Neurosci 10:281-302, 2001) HCO simple conductance-based model. The model consists of two reciprocally inhibitory neurons and replicates the electrical activity of the oscillator interneurons of the leech heartbeat central pattern generator under a variety of experimental conditions. Our long-range goal is to understand how this basic circuit building block produces functional activity under a variety of parameter regimes and how different parameter regimes influence stability and modulatability. By using the latest developments in computer technology, we simulated and stored large amounts of data (on the order of terabytes). We systematically explored the parameter space of the HCO and corresponding isolated neuron models using a brute-force approach. We varied a set of selected parameters (maximal conductance of intrinsic and synaptic currents) in all combinations, resulting in about 10 million simulations. We classified these HCO and isolated neuron model simulations by their activity characteristics into identifiable groups and quantified their prevalence. By querying the database, we compared the activity characteristics of the identified groups of our simulated HCO models with those of our simulated isolated neuron models and found that regularly bursting neurons compose only a small minority of functional HCO models; the vast majority was composed of spiking neurons.}, } @article {pmid24073105, year = {2012}, author = {Buscemi, J and Steglitz, J and Spring, B}, title = {Factors and predictors of cognitive impairment in the elderly: A synopsis and comment on "Systematic Review: Factors associated with risk for and possible prevention of cognitive decline in later life".}, journal = {Translational behavioral medicine}, volume = {2}, number = {2}, pages = {126-127}, pmid = {24073105}, issn = {1869-6716}, abstract = {The sixth column on Evidence-Based Behavioral Medicine is focused on Plassman et al.'s (Ann Internal Med 153:182-193, 2010) systematic review on factors associated with risk for and prevention of cognitive decline among the elderly. A total of 250 studies were included in the final analyses. Cognitive training was most consistently and negatively associated with cognitive decline. Evidence was largely consistent across observational and randomized controlled trial (RCT) studies. Other factors, such as physical activity, some healthy nutritional patterns, and not smoking might also be protective against cognitive decline, but the available evidence is not adequate to draw conclusions about the strength of these relationships. Future research addressing these limitations should include well-designed RCTs that attempt to replicate the finding that cognitive training is protective, and well as high-quality observational and interventional studies that examine the impact of health behaviors on cognitive decline.}, } @article {pmid22648155, year = {2012}, author = {Garratt, M and Brooks, RC}, title = {Oxidative stress and condition-dependent sexual signals: more than just seeing red.}, journal = {Proceedings. Biological sciences}, volume = {279}, number = {1741}, pages = {3121-3130}, pmid = {22648155}, issn = {1471-2954}, mesh = {Animals ; Antioxidants/metabolism ; Birds/metabolism/physiology ; Female ; Humans ; Male ; Mice ; Oxidative Stress/*physiology ; Sex Characteristics ; Sexual Behavior, Animal/*physiology ; Signal Transduction/*physiology ; }, abstract = {The links between fitness, health, sexual signals and mate choice are complex and subject to ongoing study. In 1999, von Schantz et al. made the valuable suggestion that oxidative stress may be an important missing piece of this complex puzzle. Their suggestion has been enthusiastically tested, with over 300 studies citing their paper, but most effort has concerned carotenoid-based (and to a lesser extent melanin-based) visual signals, predominantly in birds and fishes. Today, we know a great deal more about oxidative stress and related physiology, in both a pathological and regulatory sense, than we did in 1999. We revisit von Schantz et al.'s predictions and, more importantly, highlight novel mechanisms that could link oxidative stress with a range of energetically demanding signals, greatly increasing the scope from visual signalling systems that are usually discussed and nearly always tested. In particular, we argue that differences between individuals in their ability to regulate physiology related to oxidative stress may be an important factor influencing the production of sexual signals and the costs that are incurred from investment.}, } @article {pmid22647288, year = {2014}, author = {Hodgson, K and Hutchinson, AD and Denson, L}, title = {Nonpharmacological treatments for ADHD: a meta-analytic review.}, journal = {Journal of attention disorders}, volume = {18}, number = {4}, pages = {275-282}, doi = {10.1177/1087054712444732}, pmid = {22647288}, issn = {1557-1246}, mesh = {Attention Deficit Disorder with Hyperactivity/psychology/*therapy ; Behavior Therapy ; Child ; Child, Preschool ; Controlled Clinical Trials as Topic ; Female ; Humans ; Male ; Neurofeedback ; Sex Factors ; Treatment Outcome ; }, abstract = {OBJECTIVE: The authors replicated and expanded on Fabiano et al.'s meta-analysis of behavioral treatments for ADHD, systematically comparing the efficacy of 7 nonpharmacological interventions.

METHOD: A total of 14 controlled treatment studies conducted post-1994-evaluating behavior modification, neurofeedback therapy, multimodal psychosocial treatment, school-based programs, working memory training, parent training, and self-monitoring-were identified, primarily by searching electronic English-language databases. The results were meta-analyzed: mean-weighted effect sizes for the treatment outcomes of 625 participants (382 treatment, 243 controls) were calculated, and moderator analyses examined contributions of gender, ADHD subtype, and treatment "dosage" to outcome.

RESULTS: Behavior modification and neurofeedback treatments were most supported by this evidence. Interventions were generally more efficacious for girls, and least efficacious for the "combined" ADHD subtype. The authors found no dose or age effects.

CONCLUSION: Based on the small, published literature, this study supports some nonpharmacological interventions for ADHD, and indicates directions for more evaluation research into psychological treatments.}, } @article {pmid22644788, year = {2012}, author = {Cheu, EY and Yu, J and Tan, CH and Tang, H}, title = {Synaptic conditions for auto-associative memory storage and pattern completion in Jensen et al.'s model of hippocampal area CA3.}, journal = {Journal of computational neuroscience}, volume = {33}, number = {3}, pages = {435-447}, pmid = {22644788}, issn = {1573-6873}, mesh = {Action Potentials/physiology ; Association Learning/physiology ; CA3 Region, Hippocampal/cytology/*physiology ; Computer Simulation ; Humans ; Interneurons/physiology ; Memory/*physiology ; Memory, Long-Term/physiology ; Memory, Short-Term/physiology ; *Models, Neurological ; Neural Networks, Computer ; Pattern Recognition, Physiological/*physiology ; Pyramidal Cells/physiology ; Receptors, AMPA/physiology ; Receptors, N-Methyl-D-Aspartate/physiology ; Synapses/*physiology ; Synaptic Transmission/physiology ; }, abstract = {Jensen et al. (Learn Memory 3(2-3):243-256, 1996b) proposed an auto-associative memory model using an integrated short-term memory (STM) and long-term memory (LTM) spiking neural network. Their model requires that distinct pyramidal cells encoding different STM patterns are fired in different high-frequency gamma subcycles within each low-frequency theta oscillation. Auto-associative LTM is formed by modifying the recurrent synaptic efficacy between pyramidal cells. In order to store auto-associative LTM correctly, the recurrent synaptic efficacy must be bounded. The synaptic efficacy must be upper bounded to prevent re-firing of pyramidal cells in subsequent gamma subcycles. If cells encoding one memory item were to re-fire synchronously with other cells encoding another item in subsequent gamma subcycle, LTM stored via modifiable recurrent synapses would be corrupted. The synaptic efficacy must also be lower bounded so that memory pattern completion can be performed correctly. This paper uses the original model by Jensen et al. as the basis to illustrate the following points. Firstly, the importance of coordinated long-term memory (LTM) synaptic modification. Secondly, the use of a generic mathematical formulation (spiking response model) that can theoretically extend the results to other spiking network utilizing threshold-fire spiking neuron model. Thirdly, the interaction of long-term and short-term memory networks that possibly explains the asymmetric distribution of spike density in theta cycle through the merger of STM patterns with interaction of LTM network.}, } @article {pmid22644215, year = {2012}, author = {Prakash, S and Saini, S and Rana, KR and Mahato, P}, title = {Refining clinical features and therapeutic options of new daily persistent headache: a retrospective study of 63 patients in India.}, journal = {The journal of headache and pain}, volume = {13}, number = {6}, pages = {477-485}, pmid = {22644215}, issn = {1129-2377}, mesh = {Adolescent ; Adult ; Aged ; Analgesics/*therapeutic use ; Brain/pathology ; Female ; Follow-Up Studies ; Headache/diagnosis/*epidemiology/*therapy ; Humans ; India/epidemiology ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Pain Measurement ; Prednisolone/*analogs & derivatives/therapeutic use ; Retrospective Studies ; *Treatment Outcome ; Valproic Acid/*therapeutic use ; Young Adult ; }, abstract = {The aim of this retrospective study was to provide data on the clinical features and treatment outcomes of patients with NDPH (fulfilling Kung et al.'s criteria). A total of 63 patients were observed during a 5-yr period (2007-2012). More than one-third (35 %) patients had migrainous features; 65 % patients fulfilled the ICHD-II criteria. Both groups were similar in most clinical and epidemiological features. However, migrainous features were more common in patients with a prior history of episodic migraine (though statistically not significant). After a median follow-up of 9 months, 37 % patients showed "excellent" response (no or less than 1 headache per month). Another 30 % patients had "good" response (>50 % reduction in headache frequency or days per month). Excellent response was more in patients with a history of less than 6 months duration (statistically not significant). Patients with a recognized trigger showed better prognosis. Response was better in patients who received intravenous therapy of methyl prednisolone and sodium valproate. We suggest prospective and controlled studies to confirm our observations.}, } @article {pmid22639070, year = {2012}, author = {Gherardi, F and Aquiloni, L and Tricarico, E}, title = {Revisiting social recognition systems in invertebrates.}, journal = {Animal cognition}, volume = {15}, number = {5}, pages = {745-762}, doi = {10.1007/s10071-012-0513-y}, pmid = {22639070}, issn = {1435-9456}, mesh = {Animals ; Arthropods/physiology ; Insecta/physiology ; Invertebrates/*physiology ; Mollusca/physiology ; Recognition, Psychology ; Social Behavior ; *Social Perception ; }, abstract = {Since the 1970s, the ability of some invertebrate species to recognize individual conspecifics has attracted increased scientific interest. However, there is still confusion in the literature, possibly due to the lack of unambiguous criteria for classifying social recognition in its different forms. Here, we synthesize the results of studies on invertebrates and provide a framework with the purpose of identifying research needs and directions for future investigations. Following in part Sherman et al.'s (Behavioural ecology: an evolutionary approach. Blackwell Science, Oxford, pp 69-96, 1997) definition of 'recognition systems' and Tibbetts and Dale's (Trends Ecol Evol 22:529-537, 2007) classification of 'individual recognition,' we first discuss different case studies that exemplify the categories of 'familiar recognition' and 'class-level recognition.' Then, through the analysis of the invertebrate literature, we illustrate eight key properties that characterize 'true individual recognition' systems. We are confident that the proposed framework will provide opportunities for exciting discoveries of the cognitive abilities in invertebrates.}, } @article {pmid22624305, year = {2012}, author = {Davies, TJ and Kraft, NJ and Salamin, N and Wolkovich, EM}, title = {Incompletely resolved phylogenetic trees inflate estimates of phylogenetic conservatism.}, journal = {Ecology}, volume = {93}, number = {2}, pages = {242-247}, doi = {10.1890/11-1360.1}, pmid = {22624305}, issn = {0012-9658}, mesh = {Animals ; Computer Simulation ; Conservation of Natural Resources ; Models, Genetic ; Phylogeny ; Plants/*genetics ; Reproduction ; Species Specificity ; Time Factors ; }, abstract = {The tendency for more closely related species to share similar traits and ecological strategies can be explained by their longer shared evolutionary histories and represents phylogenetic conservatism. How strongly species traits co-vary with phylogeny can significantly impact how we analyze cross-species data and can influence our interpretation of assembly rules in the rapidly expanding field of community phylogenetics. Phylogenetic conservatism is typically quantified by analyzing the distribution of species values on the phylogenetic tree that connects them. Many phylogenetic approaches, however, assume a completely sampled phylogeny: while we have good estimates of deeper phylogenetic relationships for many species-rich groups, such as birds and flowering plants, we often lack information on more recent interspecific relationships (i.e., within a genus). A common solution has been to represent these relationships as polytomies on trees using taxonomy as a guide. Here we show that such trees can dramatically inflate estimates of phylogenetic conservatism quantified using S. P. Blomberg et al.'s K statistic. Using simulations, we show that even randomly generated traits can appear to be phylogenetically conserved on poorly resolved trees. We provide a simple rarefaction-based solution that can reliably retrieve unbiased estimates of K, and we illustrate our method using data on first flowering times from Thoreau's woods (Concord, Massachusetts, USA).}, } @article {pmid22617679, year = {2012}, author = {Weisfeld, G and LaFreniere, P}, title = {Need for more evolutionary and developmental perspective on basic emotional mechanisms.}, journal = {The Behavioral and brain sciences}, volume = {35}, number = {3}, pages = {171-172}, doi = {10.1017/S0140525X11001658}, pmid = {22617679}, issn = {1469-1825}, mesh = {Brain/*diagnostic imaging/*physiology ; Emotions/*physiology ; Humans ; *Neuroimaging ; Radiography ; }, abstract = {Lindquist et al.'s meta-analysis focuses on adult humans; the authors' emotion model might be strengthened by considering research on infants and animals, highlighting the importance of the limbic system. Reliance on the James-Lange theory is questionable; emotions typically occur instantaneously, with dubious dependence on bodily feedback for affect. Stronger evidence for localization might be obtained using more precise emotion terms and alterative localization methods.}, } @article {pmid22617671, year = {2012}, author = {Scherer, KR}, title = {Neuroscience findings are consistent with appraisal theories of emotion; but does the brain "respect" constructionism?.}, journal = {The Behavioral and brain sciences}, volume = {35}, number = {3}, pages = {163-164}, doi = {10.1017/S0140525X11001750}, pmid = {22617671}, issn = {1469-1825}, mesh = {Brain/*diagnostic imaging/*physiology ; Emotions/*physiology ; Humans ; *Neuroimaging ; Radiography ; }, abstract = {I reject Lindquist et al.'s implicit claim that all emotion theories other than constructionist ones subscribe to a "brain locationist" approach. The neural mechanisms underlying relevance detection, reward, attention, conceptualization, or language use are consistent with many theories of emotion, in particular componential appraisal theories. I also question the authors' claim that the meta-analysis they report provides support for the specific assumptions of constructionist theories.}, } @article {pmid22617661, year = {2012}, author = {Humeny, C and Kelly, D and Brook, A}, title = {Further routes to psychological constructionism.}, journal = {The Behavioral and brain sciences}, volume = {35}, number = {3}, pages = {153-154}, doi = {10.1017/S0140525X11001518}, pmid = {22617661}, issn = {1469-1825}, mesh = {Brain/*diagnostic imaging/*physiology ; Emotions/*physiology ; Humans ; *Neuroimaging ; Radiography ; }, abstract = {In this commentary, we do two things. First, we sketch two further routes to psychological constructionism. They are complementary to Lindquist et al.'s meta-analyses and have potential to add new evidence. Second, we look at a challenging kind of case for constructionism, namely, emotional anomalies where there are correlated, and probably relevant, brain anomalies. Psychopaths are our example.}, } @article {pmid22617659, year = {2012}, author = {Hamann, S}, title = {What can neuroimaging meta-analyses really tell us about the nature of emotion?.}, journal = {The Behavioral and brain sciences}, volume = {35}, number = {3}, pages = {150-152}, doi = {10.1017/S0140525X11001701}, pmid = {22617659}, issn = {1469-1825}, mesh = {Brain/*diagnostic imaging/*physiology ; Emotions/*physiology ; Humans ; *Neuroimaging ; Radiography ; }, abstract = {In Vytal and Hamann (2010) we reported a neuroimaging meta-analysis that found that basic emotions can be distinguished by their brain activation correlates, in marked contrast to Lindquist et al.'s conclusions in the target article. Here, I discuss implications of these findings for understanding emotion, outline limitations of using meta-analyses and neuroimaging as the sole basis for deciding between emotion views, and suggest that these views are essentially compatible and could be adapted and combined into an integrated emotion framework.}, } @article {pmid22617655, year = {2012}, author = {Cramer, AO and Kendler, KS and Borsboom, D}, title = {A constructionist account of emotional disorders.}, journal = {The Behavioral and brain sciences}, volume = {35}, number = {3}, pages = {146-147}, doi = {10.1017/S0140525X11001488}, pmid = {22617655}, issn = {1469-1825}, mesh = {Brain/*diagnostic imaging/*physiology ; Emotions/*physiology ; Humans ; *Neuroimaging ; Radiography ; }, abstract = {Lindquist et al. present a strong case for a constructionist account of emotion. First, we elaborate on the ramifications that a constructionist account of emotions might have for psychiatric disorders with emotional disturbances as core elements. Second, we reflect on similarities between Lindquist et al.'s model and recent attempts at formulating psychiatric disorders as networks of causally related symptoms.}, } @article {pmid22606851, year = {2012}, author = {Barnes, MJ}, title = {Comments on Dr. Matos, et al.'s article (pps. 255-260) in CRANIO october 2011 issue.}, journal = {Cranio : the journal of craniomandibular practice}, volume = {30}, number = {2}, pages = {92-3; author reply 93-4}, pmid = {22606851}, issn = {0886-9634}, mesh = {Electromyography/*methods ; Humans ; Masticatory Muscles/*physiopathology ; Temporomandibular Joint Disorders/*diagnosis ; *Vertical Dimension ; }, } @article {pmid22593625, year = {2012}, author = {Yang, J and Rayner, K and Li, N and Wang, S}, title = {Is preview benefit from word n + 2 a common effect in reading Chinese? Evidence from eye movements.}, journal = {Reading and writing}, volume = {25}, number = {5}, pages = {1079-1091}, pmid = {22593625}, issn = {0922-4777}, support = {R01 HD026765/HD/NICHD NIH HHS/United States ; R37 HD026765/HD/NICHD NIH HHS/United States ; }, abstract = {Although most studies of reading English (and other alphabetic languages) have indicated that readers do not obtain preview benefit from word n + 2, Yang, Wang, Xu, and Rayner (2009) reported evidence that Chinese readers obtain preview benefit from word n + 2. However, this effect may not be common in Chinese because the character prior to the target word in Yang et al.'s experiment was always a very high frequency function word. In the current experiment, we utilized a relatively low frequency word n + 1 to examine whether an n + 2 preview benefit effect would still exist and failed to find any preview benefit from word n + 2. These results are consistent with a recent study which indicated that foveal load modulates the perceptual span during Chinese reading (Yan, Kliegl, Shu, Pan, & Zhou, 2010). Implications of these results for models of eye movement control are discussed.}, } @article {pmid22585760, year = {2012}, author = {Clark Barrett, H and Stich, S and Laurence, S}, title = {Should the study of Homo sapiens be part of cognitive science?.}, journal = {Topics in cognitive science}, volume = {4}, number = {3}, pages = {379-386}, doi = {10.1111/j.1756-8765.2012.01194.x}, pmid = {22585760}, issn = {1756-8765}, mesh = {*Anthropology ; *Cognition ; *Cognitive Science ; Humans ; *Research Design ; }, abstract = {Beller, Bender, and Medin argue that a reconciliation between anthropology and cognitive science seems unlikely. We disagree. In our view, Beller et al.'s view of the scope of what anthropology can offer cognitive science is too narrow. In focusing on anthropology's role in elucidating cultural particulars, they downplay the fact that anthropology can reveal both variation and universals in human cognition, and is in a unique position to do so relative to the other subfields of cognitive science. Indeed, without cross-cultural research, the universality of any aspect of human cognition cannot truly be established. Therefore, if the goal of cognitive science is to understand the cognitive capacities of our species as a whole, then it cannot do without anthropology. We briefly review a growing body of anthropological work aimed at answering questions about human cognition and offer suggestions for future work.}, } @article {pmid22582834, year = {2013}, author = {Michael, GA and Lété, B and Ducrot, S}, title = {Trajectories of attentional development: an exploration with the master activation map model.}, journal = {Developmental psychology}, volume = {49}, number = {4}, pages = {615-631}, doi = {10.1037/a0028410}, pmid = {22582834}, issn = {1939-0599}, mesh = {Attention/*physiology ; Child ; Child Development/*physiology ; Female ; Human Development/physiology ; Humans ; *Inhibition, Psychological ; Male ; Models, Psychological ; Pattern Recognition, Visual/physiology ; Reaction Time ; Young Adult ; }, abstract = {The developmental trajectories of several attention components, such as orienting, inhibition, and the guidance of selection by relevance (i.e., advance knowledge relevant to the task) were investigated in 498 participants (ages 7, 8, 9, 10, 11, and 20). The paradigm was based on Michael et al.'s (2006) master activation map model and consisted of 3 visual search tasks presented in an intrasubject Latin square design and differing in terms of the probability with which a salient signal was associated with the target or a distractor. The results suggest that, whereas computations of salience were already proficient at age 7, and the use of advance knowledge was efficient throughout childhood, albeit without reaching adult levels, the integration of salience and relevance reached its asymptotic level at age 8. Although moving and engaging attention was proficient at age 7, disengaging attention started to improve at age 9, reaching its adult level at age 11. As regards inhibition of salient distractors, the authors found no developmental pattern before adulthood, regardless of whether advance knowledge was available about the distractor or not, although all participants were able to use such knowledge to reduce overall interference. Finally, some results suggest that the control of resources for strengthening inhibition becomes efficient between ages 9 and 10. The developmental trajectories were compared with the existing literature and discussed.}, } @article {pmid22581317, year = {2014}, author = {Lord, BD and Gramling, SE}, title = {Patterns of religious coping among bereaved college students.}, journal = {Journal of religion and health}, volume = {53}, number = {1}, pages = {157-177}, pmid = {22581317}, issn = {1573-6571}, mesh = {Adaptation, Psychological/*physiology ; *Bereavement ; Factor Analysis, Statistical ; Female ; Humans ; Male ; *Religion and Psychology ; Southeastern United States ; Students/*psychology/statistics & numerical data ; Surveys and Questionnaires ; Universities ; Young Adult ; }, abstract = {Contemporary research has suggested that bereavement is a paramount issue in college populations, a group which has historically been underrepresented in grief research (Balk. in Death studies 25:67-84, 2001; Balk et al. in Death Studies 34:459-468, 2010). Indeed, there has been a call to generate new research on grief with specific populations and age groups (Center for the Advancement of Health. in Death Studies 28:568-575, 2004). Religion is often described as a primary way that individuals cope with bereavement in particular (Frantz et al. in Pastor Psychol 44(3):151-163, 1996) and has been shown to effect college student reactions to stress in general (Merrill et al. in Mental Health, Religion & Culture 12(5):501-511, 2009). The RCOPE (Pargament et al. in J Clin Psychol 56(4):519-543, 2000, J Health Psychol 9:713-730, 2004) is a frequently used measure of religious coping, but has not been evaluated with a bereaved undergraduate population. Given that emerging adulthood is a critical developmental phase of religious identity (Fowler. in New Directions for Child Development 3(52):27-45, 1991), the current study examined the factor structure of the RCOPE within a sample of bereaved college students. An exploratory factor analysis was performed, which approximated the factor structure proposed by Pargament et al. (J Clin Psychol 56(4):519-543, 2000). However, a high correlation between the positive and negative religious coping subscales (r = 0.71) detracted from the predictive utility of Pargament et al.'s (2000) two overarching subscales. Therefore, an exploratory factor analysis with an orthogonal rotation was used to identify two uncorrelated subscales (adaptive religious coping and maladaptive religious coping). This new two-factor, 39-item version of the RCOPE was found to demonstrate good internal consistency (α > 0.8) as well as convergent and discriminant validity. The interaction between religious coping strategies and core beliefs about the predictability of the world is explored, and directions for future research and clinical practice are suggested.}, } @article {pmid22569106, year = {2012}, author = {VanderWeele, TJ and Hernán, MA}, title = {Results on differential and dependent measurement error of the exposure and the outcome using signed directed acyclic graphs.}, journal = {American journal of epidemiology}, volume = {175}, number = {12}, pages = {1303-1310}, pmid = {22569106}, issn = {1476-6256}, support = {R01 HL080644/HL/NHLBI NIH HHS/United States ; R03 HD060696/HD/NICHD NIH HHS/United States ; HL080644/HL/NHLBI NIH HHS/United States ; R01 ES017876/ES/NIEHS NIH HHS/United States ; HD060696/HD/NICHD NIH HHS/United States ; ES017876/ES/NIEHS NIH HHS/United States ; }, mesh = {*Bias ; *Causality ; Confounding Factors, Epidemiologic ; Data Interpretation, Statistical ; *Epidemiologic Research Design ; Models, Statistical ; }, abstract = {Measurement error in both the exposure and the outcome is a common problem in epidemiologic studies. Measurement errors in the exposure and the outcome are said to be independent of each other if the measured exposure and the measured outcome are statistically independent conditional on the true exposure and true outcome (and dependent otherwise). Measurement error is said to be nondifferential if measurement of the exposure does not depend on the true outcome conditional on the true exposure and vice versa; otherwise it is said to be differential. Few results on differential and dependent measurement error are available in the literature. Here the authors use formal rules governing associations on signed directed acyclic graphs (DAGs) to draw conclusions about the presence and sign of causal effects under differential and dependent measurement error. The authors apply these rules to 4 forms of measurement error: independent nondifferential, dependent nondifferential, independent differential, and dependent differential. For a binary exposure and outcome, the authors generalize Weinberg et al.'s (Am J Epidemiol. 1994;140(6):565-571) result for nondifferential measurement error on preserving the direction of a trend to settings which also allow measurement error in the outcome and to cases involving dependent and/or differential error.}, } @article {pmid22562005, year = {2012}, author = {Markowski-Lindsay, M and Catanzaro, P and Damery, D and Kittredge, DB and Butler, BJ and Stevens, T}, title = {Forest-based biomass supply in Massachusetts: how much is there and how much is available.}, journal = {Journal of environmental management}, volume = {106}, number = {}, pages = {1-7}, doi = {10.1016/j.jenvman.2012.03.051}, pmid = {22562005}, issn = {1095-8630}, mesh = {*Biomass ; Massachusetts ; Ownership ; *Renewable Energy ; *Trees ; }, abstract = {Forest owners in Massachusetts (U.S.) live in a densely populated state and near forestland that is under pressure of development and characterized by small parcel size. Forest-based biomass harvesting in Massachusetts is a renewable energy topic generating a great deal of discussion among all constituents. To provide perspective on these discussions, our analysis asks how much forested land in Massachusetts could be available for biomass supply. This analysis considers the level of bioenergy production that could be maintained on an annual basis given the amount of woody biomass that is likely to be supplied from private- and state-owned Massachusetts forests, which comprises nearly 90% of the state's forests. Applying the most recent information on forest ownership and owner attitudes in Massachusetts, we estimate that between 80,000 and 369,000 dry tons/year of available wood-based biomass from forest management practices on private- and state-owned forests, or between 1.4 trillion and 6.2 trillion BTUs/year. These estimates represent between 0.09% and 0.42% of all Massachusetts residential, commercial and industrial annual consumption. These estimates are well below Kelty et al.'s (2008) estimate of 891,000 dry tons/year; the largest factors in this reduction are the reduced contribution of biomass due to social constraints and the amount of state land considered to be open to active management. Conversations regarding the use of biomass and its impacts on forests, as well as the development of biomass-related policy, should consider the supply of biomass that is likely available. While overall forest inventory estimates suggest one degree of availability, our research suggests that this needs to be tempered with the reality of ownership size and owner attitudes.}, } @article {pmid22558322, year = {2012}, author = {Ma, X and Hamadeh, MJ and Christie, BR and Foster, JA and Tarnopolsky, MA}, title = {Impact of treadmill running and sex on hippocampal neurogenesis in the mouse model of amyotrophic lateral sclerosis.}, journal = {PloS one}, volume = {7}, number = {4}, pages = {e36048}, pmid = {22558322}, issn = {1932-6203}, mesh = {8-Hydroxy-2'-Deoxyguanosine ; Amyotrophic Lateral Sclerosis/genetics/*pathology/*physiopathology ; Animals ; Bromodeoxyuridine/metabolism ; Cell Proliferation ; Cell Survival ; Dentate Gyrus/metabolism/pathology ; Deoxyguanosine/analogs & derivatives/metabolism ; Disease Models, Animal ; *Exercise Test ; Female ; Gene Expression Regulation ; Hippocampus/pathology/*physiopathology ; Intercellular Signaling Peptides and Proteins/genetics/metabolism ; Male ; Mice ; Neurogenesis ; Neurons/metabolism/pathology ; Oxidative Stress ; Phenotype ; *Physical Conditioning, Animal ; RNA, Messenger/genetics/metabolism ; *Sex Characteristics ; Tyrosine/analogs & derivatives/metabolism ; }, abstract = {Hippocampal neurogenesis in the subgranular zone (SGZ) of dentate gyrus (DG) occurs throughout life and is regulated by pathological and physiological processes. The role of oxidative stress in hippocampal neurogenesis and its response to exercise or neurodegenerative diseases remains controversial. The present study was designed to investigate the impact of oxidative stress, treadmill exercise and sex on hippocampal neurogenesis in a murine model of heightened oxidative stress (G93A mice). G93A and wild type (WT) mice were randomized to a treadmill running (EX) or a sedentary (SED) group for 1 or 4 wk. Immunohistochemistry was used to detect bromodeoxyuridine (BrdU) labeled proliferating cells, surviving cells, and their phenotype, as well as for determination of oxidative stress (3-NT; 8-OHdG). BDNF and IGF1 mRNA expression was assessed by in situ hybridization. Results showed that: (1) G93A-SED mice had greater hippocampal neurogenesis, BDNF mRNA, and 3-NT, as compared to WT-SED mice. (2) Treadmill running promoted hippocampal neurogenesis and BDNF mRNA content and lowered DNA oxidative damage (8-OHdG) in WT mice. (3) Male G93A mice showed significantly higher cell proliferation but a lower level of survival vs. female G93A mice. We conclude that G93A mice show higher hippocampal neurogenesis, in association with higher BDNF expression, yet running did not further enhance these phenomena in G93A mice, probably due to a 'ceiling effect' of an already heightened basal levels of hippocampal neurogenesis and BDNF expression.}, } @article {pmid22553832, year = {2012}, author = {Zhang, S and Ahn, C}, title = {Sample size calculation for time-averaged differences in the presence of missing data.}, journal = {Contemporary clinical trials}, volume = {33}, number = {3}, pages = {550-556}, pmid = {22553832}, issn = {1559-2030}, support = {UL1 RR024982/RR/NCRR NIH HHS/United States ; R01 DK081872/DK/NIDDK NIH HHS/United States ; P50CA70907/CA/NCI NIH HHS/United States ; P30CA142543/CA/NCI NIH HHS/United States ; P30 CA142543/CA/NCI NIH HHS/United States ; UL1 RR024982/RR/NCRR NIH HHS/United States ; DK081872/DK/NIDDK NIH HHS/United States ; P50 CA070907/CA/NCI NIH HHS/United States ; }, mesh = {Data Collection/*methods ; *Data Interpretation, Statistical ; Humans ; *Sample Size ; Statistics as Topic/methods ; Time Factors ; }, abstract = {Sample size calculations based on two-sample comparisons of slopes in repeated measurements have been reported by many investigators. In contrast, the literature has paid relatively little attention to the sample size calculations for time-averaged differences in the presence of missing data in repeated measurement studies. Diggle et al. (2002) provided a sample size formula detecting time-averaged differences for continuous outcomes in repeated measurement studies assuming no missing data and the compound symmetry (CS) correlation structure among outcomes from the same subject. In this paper we extend Diggle et al.'s timeaveraged difference sample size formula by allowing missing data and various correlation structures. We propose to use the generalized estimating equation (GEE) method to compare the time-averaged differences in repeatedmeasurement studies and introduce a closed form formula for sample size and power. Simulation studies were conducted to investigate the performance of GEE sample size formula with small sample sizes, a damped exponential family of correlation structures and missing data. The proposed sample size formula is illustrated using a clinical trial example.}, } @article {pmid22536840, year = {2013}, author = {Scott, SE and Walter, FM and Webster, A and Sutton, S and Emery, J}, title = {The model of pathways to treatment: conceptualization and integration with existing theory.}, journal = {British journal of health psychology}, volume = {18}, number = {1}, pages = {45-65}, doi = {10.1111/j.2044-8287.2012.02077.x}, pmid = {22536840}, issn = {2044-8287}, mesh = {*Concept Formation ; Decision Making ; Humans ; Mental Disorders/*diagnosis/psychology/*therapy ; *Mental Health Services ; *Models, Theoretical ; *Psychological Theory ; }, abstract = {BACKGROUND: Studying and understanding pathways to diagnosis and treatment is vital for the development of successful interventions to encourage early detection, presentation, and diagnosis. An existing framework posited to describe the decisional and behavioural processes that occur prior to treatment (Andersen et al.'s General Model of Total Patient Delay) does not appear to match the complex and dynamic nature of the pathways into and through the health care system or provide a clear framework for research. Therefore a revised descriptive framework, the Model of Pathways to Treatment, has been proposed.

PURPOSE: This paper presents the concepts and definitions of the Model of Pathways to Treatment and specifies how the model can encompass existing psychological theory, with particular focus on the Appraisal and Help-seeking intervals. The potential and direction for future work is also discussed.

STATEMENT OF CONTRIBUTION: WHAT IS ALREADY KNOWN ON THIS SUBJECT?: • The use of theory is often lacking in existing research into delays in presentation, diagnosis and treatment of illness. WHAT DOES THIS STUDY ADD?: • A detailed account of the concepts and definitions of a revised framework: the Model of Pathways to Treatment. • Specification of how the Model of Pathways to Treatment can encompass existing psychological theory such as the Common Sense Model of Illness Self-regulation and Social Cognitive Theory.}, } @article {pmid22531641, year = {2012}, author = {Beenstock, J and Sniehotta, FF and White, M and Bell, R and Milne, EM and Araujo-Soares, V}, title = {What helps and hinders midwives in engaging with pregnant women about stopping smoking? A cross-sectional survey of perceived implementation difficulties among midwives in the North East of England.}, journal = {Implementation science : IS}, volume = {7}, number = {}, pages = {36}, pmid = {22531641}, issn = {1748-5908}, support = {G0900686/MRC_/Medical Research Council/United Kingdom ; /BHF_/British Heart Foundation/United Kingdom ; /CRUK_/Cancer Research UK/United Kingdom ; }, mesh = {Cross-Sectional Studies ; England ; Female ; *Guideline Adherence ; Health Care Surveys ; *Health Knowledge, Attitudes, Practice ; Humans ; *Midwifery ; Pregnancy ; *Prenatal Care ; Principal Component Analysis ; Referral and Consultation ; *Smoking Cessation ; }, abstract = {BACKGROUND: Around 5,000 miscarriages and 300 perinatal deaths per year result from maternal smoking in the United Kingdom. In the northeast of England, 22% of women smoke at delivery compared to 14% nationally. Midwives have designated responsibilities to help pregnant women stop smoking. We aimed to assess perceived implementation difficulties regarding midwives' roles in smoking cessation in pregnancy.

METHODS: A self-completed, anonymous survey was sent to all midwives in northeast England (n = 1,358) that explores the theoretical explanations for implementation difficulties of four behaviours recommended in the National Institute for Health and Clinical Excellence (NICE) guidance: (a) asking a pregnant woman about her smoking behaviour, (b) referring to the stop-smoking service, (c) giving advice about smoking behaviour, and (d) using a carbon monoxide monitor. Questions covering Michie et al.'s theoretical domain framework (TDF), describing 11 domains of hypothesised behavioural determinants (i.e., 'knowledge', 'skills', 'social/professional role/identity', 'beliefs about capabilities', 'beliefs about consequences', 'motivation and goals', 'memory', 'attention and decision processes', 'environmental context and resources', 'social influences', 'emotion', and 'self-regulation/action planning'), were used to describe perceived implementation difficulties, predict self-reported implementation behaviours, and explore relationships with demographic and professional variables.

RESULTS: The overall response rate was 43% (n = 589). The number of questionnaires analysed was 364, following removal of the delivery-unit midwives, who are not directly involved in providing smoking-cessation services. Participants reported few implementation difficulties, high levels of motivation for all four behaviours and identified smoking-cessation work with their role. Midwives were less certain about the consequences of, and the environmental context and resources available for, engaging in this work relative to other TDF domains. All domains were highly correlated. A principal component analysis showed that a single factor ('propensity to act'), derived from all domains, explained 66% of variance in theoretical domain measures. The 'propensity to act' was predictive of the self-reported behaviour 'Refer all women who smoke……to NHS Stop Smoking Services' and mediated the relationship between demographic variables, such as midwives' main place of work, and behaviour.

CONCLUSIONS: Our findings advance understanding of what facilitates and inhibits midwives' guideline implementation behaviours in relation to smoking cessation and will inform the development of current practice and new interventions. Using the TDF as a self-completion questionnaire is innovative, and this study supports previous research that the TDF is an appropriate tool to understand the behaviour of healthcare professionals.}, } @article {pmid22527784, year = {2012}, author = {Zhu, Z}, title = {An efficient authentication scheme for telecare medicine information systems.}, journal = {Journal of medical systems}, volume = {36}, number = {6}, pages = {3833-3838}, pmid = {22527784}, issn = {0148-5598}, mesh = {*Access to Information ; *Computer Security ; Confidentiality ; Medical Informatics ; *Telemedicine ; }, abstract = {To ensure patients' privacy, such as telephone number, medical record number, health information, etc., authentication schemes for telecare medicine information systems (TMIS) have been studied widely. Recently, Wei et al. proposed an efficient authentication scheme for TMIS. They claimed their scheme could resist various attacks. However, in this paper, we will show their scheme is vulnerable to an off-line password guessing attack when user's smart card is lost. To improve the security, we propose a new authentication scheme for TMIS. The analysis shows our scheme could overcome the weaknesses in Wei et al.'s scheme and has better performance than their scheme.}, } @article {pmid22521685, year = {2012}, author = {Clegg, M and Towner, A and Wylie, K}, title = {Should questionnaires of female sexual dysfunction be used in routine clinical practice?.}, journal = {Maturitas}, volume = {72}, number = {2}, pages = {160-164}, doi = {10.1016/j.maturitas.2012.03.009}, pmid = {22521685}, issn = {1873-4111}, mesh = {Clinical Competence ; Cost-Benefit Analysis ; Female ; Humans ; Practice Guidelines as Topic/*standards ; Prevalence ; Sexual Dysfunction, Physiological/*diagnosis/epidemiology ; Surveys and Questionnaires/*statistics & numerical data ; }, abstract = {AIMS: The aim of this paper is to explore the potential value of questionnaires in routine clinical practice to assess female sexual dysfunction (FSD), and to identify if this could increase the competence of a physician in the initial management of women with these problems. The rationale to encourage Health Care Professionals (HCPs) to engage women in dialogue about their sexual health is that it may enhance a woman's quality of life (which may lead to improved general health) and might lead to timely interventions and possible preventative measures for certain diseases.

METHOD: A short literature review of the most relevant publications was undertaken evaluating current practice.

RESULTS: FSD can have a negative impact on women's well-being and can also be an early symptom of underlying disease. Many HCPs do not broach the subject, consequently women do not get the opportunity either to voice their sexual concerns or access appropriate services. Review of currently available FSD questionnaires suggests that many but not all are generally inappropriate for use in routine clinical practice. Kriston et al.'s STEFFI-2 may be an appropriate starting point. Evidence suggests that this would facilitate discussion of sexual matters between the HCP and the women, and increase the likelihood of FSD being diagnosed.

CONCLUSIONS: Following this review of the literature, the authors strongly recommend that HCPs include FSD questionnaires as part of their routine engagement with women. However, the questionnaire would need to be used as part of the overall assessment and cannot replace a detailed case history and examination, which should lead to effective treatment and management of FSD. The authors recommend further research in the following areas: • Effective training for HCPs. • FSD as an early presentation of sub-clinical disease. • The cost-benefit of early treatment of FSD. • A standardised, validated FSD screening tool. • Benefits of using FSD screener in routine clinical practice.}, } @article {pmid22508963, year = {2012}, author = {Kharche, S and Adeniran, I and Stott, J and Law, P and Boyett, MR and Hancox, JC and Zhang, H}, title = {Pro-arrhythmogenic effects of the S140G KCNQ1 mutation in human atrial fibrillation - insights from modelling.}, journal = {The Journal of physiology}, volume = {590}, number = {18}, pages = {4501-4514}, pmid = {22508963}, issn = {1469-7793}, support = {081809/Z/06/Z//Wellcome Trust/United Kingdom ; FS/08/021//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Action Potentials/physiology ; Atrial Fibrillation/*genetics/*physiopathology ; Computer Simulation ; Heart Atria/physiopathology ; Humans ; KCNQ1 Potassium Channel/*physiology ; *Models, Cardiovascular ; Mutation ; }, abstract = {Functional analysis has shown that the missense gain-in-function KCNQ1 S140G mutation associated with familial atrial fibrillation produces an increase of the slow delayed rectifier potassium current (I(Ks)). Through computer modelling, this study investigated mechanisms by which the KCNQ1 S140G mutation promotes and perpetuates atrial fibrillation. In simulations, Courtemanche et al.'s model of human atrial cell action potentials (APs) was modified to incorporate experimental data on changes of I(Ks) induced by the KCNQ1 S140G mutation. The cell models for wild type (WT) and mutant type (MT) I(Ks) were incorporated into homogeneous multicellular 2D and 3D tissue models. Effects of the mutation were quantified on AP profile, AP duration (APD) restitution, effective refractory period (ERP) restitution, and conduction velocity (CV) restitution.Temporal and spatial vulnerabilities of atrial tissue to genesis of re-entry were computed. Dynamic behaviours of re-entrant excitation waves (lifespan (LS), tip meandering patterns and dominant frequency) in 2D and 3D models were characterised. It was shown that the KCNQ1 S140G mutation abbreviated atrial APD and ERP and flattened APD and ERP restitution curves. It reduced atrial CV at low excitation rates, but increased it at high excitation rates that facilitated the conduction of high rate atrial excitation waves. Although it increased slightly tissue temporal vulnerability for initiating re-entry, it reduced markedly the minimal substrate size necessary for sustaining re-entry (increasing the tissue spatial vulnerability). In the 2D and 3D models, the mutation also stabilized and accelerated re-entrant excitation waves, leading to rapid and sustained re-entry. In the 3D model, scroll waves under the mutation condition MT conditions also degenerated into persistent and erratic wavelets, leading to fibrillation. In conclusion, increased I(Ks) due to the KCNQ1 S140G mutation increases atrial susceptibility to arrhythmia due to increased tissue vulnerability, shortened ERP and altered atrial conduction velocity, which, in combination, facilitate initiation and maintenance of re-entrant excitation waves.}, } @article {pmid22496670, year = {2012}, author = {Ueki, M and Cordell, HJ}, title = {Improved statistics for genome-wide interaction analysis.}, journal = {PLoS genetics}, volume = {8}, number = {4}, pages = {e1002625}, pmid = {22496670}, issn = {1553-7404}, support = {087436//Wellcome Trust/United Kingdom ; }, mesh = {Genome-Wide Association Study/*statistics & numerical data ; Humans ; *Models, Statistical ; }, abstract = {Recently, Wu and colleagues [1] proposed two novel statistics for genome-wide interaction analysis using case/control or case-only data. In computer simulations, their proposed case/control statistic outperformed competing approaches, including the fast-epistasis option in PLINK and logistic regression analysis under the correct model; however, reasons for its superior performance were not fully explored. Here we investigate the theoretical properties and performance of Wu et al.'s proposed statistics and explain why, in some circumstances, they outperform competing approaches. Unfortunately, we find minor errors in the formulae for their statistics, resulting in tests that have higher than nominal type 1 error. We also find minor errors in PLINK's fast-epistasis and case-only statistics, although theory and simulations suggest that these errors have only negligible effect on type 1 error. We propose adjusted versions of all four statistics that, both theoretically and in computer simulations, maintain correct type 1 error rates under the null hypothesis. We also investigate statistics based on correlation coefficients that maintain similar control of type 1 error. Although designed to test specifically for interaction, we show that some of these previously-proposed statistics can, in fact, be sensitive to main effects at one or both loci, particularly in the presence of linkage disequilibrium. We propose two new "joint effects" statistics that, provided the disease is rare, are sensitive only to genuine interaction effects. In computer simulations we find, in most situations considered, that highest power is achieved by analysis under the correct genetic model. Such an analysis is unachievable in practice, as we do not know this model. However, generally high power over a wide range of scenarios is exhibited by our joint effects and adjusted Wu statistics. We recommend use of these alternative or adjusted statistics and urge caution when using Wu et al.'s originally-proposed statistics, on account of the inflated error rate that can result.}, } @article {pmid22495970, year = {2012}, author = {Glauser, TA and Nevins, PH and Williamson, JC and Abdolrasulnia, M and Salinas, GD and Zhang, J and Debonnett, L and Riekert, KA}, title = {Adherence to the 2007 cystic fibrosis pulmonary guidelines: a national survey of CF care centers.}, journal = {Pediatric pulmonology}, volume = {47}, number = {5}, pages = {434-440}, doi = {10.1002/ppul.21573}, pmid = {22495970}, issn = {1099-0496}, mesh = {Adolescent ; Adult ; Anti-Bacterial Agents/therapeutic use ; Attitude of Health Personnel ; Child ; Cystic Fibrosis/complications/*therapy ; Deoxyribonuclease I/therapeutic use ; Female ; Guideline Adherence/*statistics & numerical data ; Health Care Surveys/*statistics & numerical data ; Humans ; Macrolides/therapeutic use ; Male ; Middle Aged ; *Practice Guidelines as Topic ; Tobramycin/therapeutic use ; Treatment Outcome ; Young Adult ; }, abstract = {OBJECTIVE: To examine cystic fibrosis (CF) physician adherence to the 2007 CF Foundation (CFF) Pulmonary Guidelines for Chronic Medications. Specifically adherence and barriers to prescribing level A medication recommendations (i.e., inhaled tobramycin and dornase alfa) and level B medication recommendations (i.e., macrolide antibiotics and hypertonic saline) were studied.

METHODS: During Spring 2010, the CFF emailed survey invitations to directors of 136 accredited CF care centers treating 50+ CF patients. Directors were asked to forward the invitations to their physician colleagues. One hundred thirty-three surveys were included in the analyses, representing 92 centers. Barriers were conceptualized based on Cabana et al.'s framework for adherence to guidelines. Adherence was assessed via a case vignette.

RESULTS: Logistic regression analysis revealed that higher outcome expectancy (OR = 1.099, CI 1.010-1.196) and fewer environmental/system barriers (OR = 1.484, CI 1.158-1.902) were significantly associated with Vignette Adherence. A trend for an association between Familiarity and Vignette Adherence (OR = 1.642, CI 0.953-2.828) was evident, while no demographic variables were significantly associated with Vignette Adherence.

CONCLUSION: Targeting outcome expectancy and external barriers with multifaceted, ongoing interventions may improve guideline adherence. Pulmonologists are clearly looking for empirical evidence that these medications benefit their patients over the long-term and offset patient treatment burden with improved health.}, } @article {pmid22481912, year = {2012}, author = {Narasimhadhan, AV and Rajgopal, K}, title = {FDK-Type Algorithms with No Backprojection Weight for Circular and Helical Scan CT.}, journal = {International journal of biomedical imaging}, volume = {2012}, number = {}, pages = {969432}, pmid = {22481912}, issn = {1687-4196}, abstract = {We develop two Feldkamp-type reconstruction algorithms with no backprojection weight for circular and helical trajectory with planar detector geometry. Advances in solid-state electronic detector technologies lend importance to CT systems with the equispaced linear array, the planar (flat panel) detectors, and the corresponding algorithms. We derive two exact Hilbert filtered backprojection (FBP) reconstruction algorithms with no backprojection weight for 2D fan-beam equispace linear array detector geometry (complement of the equi-angular curved array detector). Based on these algorithms, the Feldkamp-type algorithms with no backprojection weight for 3D reconstruction are developed using the standard heuristic extension of the divergent beam FBP algorithm. The simulation results show that the axial intensity drop in the reconstructed image using the FDK algorithms with no backprojection weight with circular trajectory is similar to that obtained by using Hu's and T-FDK, algorithms. Further, we present efficient algorithms to reduce the axial intensity drop encountered in the standard FDK reconstructions in circular cone-beam CT. The proposed algorithms consist of mainly two steps: reconstruction of the object using FDK algorithm with no backprojection weight and estimation of the missing term. The efficient algorithms are compared with the FDK algorithm, Hu's algorithm, T-FDK, and Zhu et al.'s algorithm in terms of axial intensity drop and noise. Simulation shows that the efficient algorithms give similar performance in axial intensity drop as that of Zhu et al.'s algorithm while one of the efficient algorithms outperforms Zhu et al.'s algorithm in terms of computational complexity.}, } @article {pmid22474411, year = {2012}, author = {Du, X and Han, L and Guo, AY and Zhao, Z}, title = {Features of methylation and gene expression in the promoter-associated CpG islands using human methylome data.}, journal = {Comparative and functional genomics}, volume = {2012}, number = {}, pages = {598987}, pmid = {22474411}, issn = {1532-6268}, support = {P30 CA068485/CA/NCI NIH HHS/United States ; P50 CA095103/CA/NCI NIH HHS/United States ; R03 LM009598/LM/NLM NIH HHS/United States ; }, abstract = {CpG islands are typically located in the 5' end of genes and considered as gene markers because they play important roles in gene regulation via epigenetic change. In this study, we compared the features of CpG islands identified by several major algorithms by setting the parameter cutoff values in order to obtain a similar number of CpG islands in a genome. This approach allows us to systematically compare the methylation and gene expression patterns in the identified CpG islands. We found that Takai and Jones' algorithm tends to identify longer CpG islands but with weaker CpG island features (e.g., lower GC content and lower ratio of the observed over expected CpGs) and higher methylation level. Conversely, the CpG clusters identified by Hackenberg et al.'s algorithm using stringent criteria are shorter and have stronger features and lower methylation level. In addition, we used the genome-wide base-resolution methylation profile in two cell lines to show that genes with a lower methylation level at the promoter-associated CpG islands tend to express in more tissues and have stronger expression. Our results validated that the DNA methylation of promoter-associated CpG islands suppresses gene expression at the genome level.}, } @article {pmid22468607, year = {2012}, author = {Kellen, D and Klauer, KC and Singmann, H}, title = {On the measurement of criterion noise in signal detection theory: the case of recognition memory.}, journal = {Psychological review}, volume = {119}, number = {3}, pages = {457-479}, doi = {10.1037/a0027727}, pmid = {22468607}, issn = {1939-1471}, mesh = {Data Interpretation, Statistical ; *Decision Making ; Humans ; *Models, Statistical ; Observer Variation ; *Psychological Theory ; Psychomotor Performance ; ROC Curve ; *Recognition, Psychology ; *Signal Detection, Psychological ; }, abstract = {Traditional approaches within the framework of signal detection theory (SDT; Green & Swets, 1966), especially in the field of recognition memory, assume that the positioning of response criteria is not a noisy process. Recent work (Benjamin, Diaz, & Wee, 2009; Mueller & Weidemann, 2008) has challenged this assumption, arguing not only for the existence of criterion noise but also for its large magnitude and substantive contribution to individuals' performance. A review of these recent approaches for the measurement of criterion noise in SDT identifies several shortcomings and confoundings. A reanalysis of Benjamin et al.'s (2009) data sets as well as the results from a new experimental method indicate that the different forms of criterion noise proposed in the recognition memory literature are of very low magnitudes, and they do not provide a significant improvement over the account already given by traditional SDT without criterion noise.}, } @article {pmid22463267, year = {2012}, author = {Zhang, Y}, title = {Comment on "Length-dependent translation of messenger RNA by ribosomes".}, journal = {Physical review. E, Statistical, nonlinear, and soft matter physics}, volume = {85}, number = {2 Pt 1}, pages = {023901}, doi = {10.1103/PhysRevE.85.023901}, pmid = {22463267}, issn = {1550-2376}, mesh = {*Models, Chemical ; *Models, Genetic ; Protein Biosynthesis/*genetics ; RNA, Messenger/*chemistry/*genetics ; Ribosomes/*chemistry/*genetics ; }, abstract = {In a recent paper by Valleriani et al. [Phys. Rev. E 83, 042903 (2011)], a simple model for the translation of messenger RNA (mRNA) is presented. Using this model, the protein translational ratio r, defined as the ratio of protein translation rate ω(tl) from mRNA to protein degradation rate ω(p), is obtained. The key point in obtaining the translational ratio r is to get the protein translation rate ω(tl). In Valleriani et al.'s paper, ω(tl) is obtained as the mean value of the measured translation rate, which is the ratio of the synthesized protein number to the mRNA lifetime. However, in experiments, different methods might be used to obtain the value of ω(tl). Therefore, to apply Valleriani et al.'s model to more general experiments, in this Comment three methods to obtain the translation rate ω(tl), and consequently the translational ratio r, are presented. Based on one of the methods which might be employed in most of the experiments, we find that the translational ratio r decays exponentially with mRNA length in prokaryotic cells, and decays reciprocally with mRNA length in eukaryotic cells. This result is slight different from that which was obtained in Valleriani et al.'s paper.}, } @article {pmid22455323, year = {2012}, author = {Edwards-Leeper, L and Spack, NP}, title = {Psychological evaluation and medical treatment of transgender youth in an interdisciplinary "Gender Management Service" (GeMS) in a major pediatric center.}, journal = {Journal of homosexuality}, volume = {59}, number = {3}, pages = {321-336}, doi = {10.1080/00918369.2012.653302}, pmid = {22455323}, issn = {1540-3602}, mesh = {Adolescent ; Age Factors ; Boston ; Child ; Female ; Gender Identity ; Humans ; Male ; Patient Care Team ; Puberty/psychology ; Puberty, Delayed/chemically induced/psychology ; Transsexualism/diagnosis/*psychology/therapy ; }, abstract = {In 2007, an interdisciplinary clinic for children and adolescents with disorders of sex development (DSD) or gender identity disorder (GID) opened in a major pediatric center. Psychometric evaluation and endocrine treatment via pubertal suppressive therapy and administration of cross-sex steroid hormones was offered to carefully selected patients according to effective protocols used in Holland. Hembree et al.'s (2009) Guidelines for Endocrine Treatment of Transsexual Persons published by the Endocrine Society endorsed these methods. A description of the clinic's protocol and general patient demographics are provided, along with treatment philosophy and goals.}, } @article {pmid22446976, year = {2012}, author = {Firesheets, EK and Francis, M and Barnum, A and Rolf, L}, title = {Community-based prevention support: using the interactive systems framework to facilitate grassroots evidenced-based substance abuse prevention.}, journal = {American journal of community psychology}, volume = {50}, number = {3-4}, pages = {347-356}, doi = {10.1007/s10464-012-9506-x}, pmid = {22446976}, issn = {1573-2770}, mesh = {Community Networks/*organization & administration ; Cooperative Behavior ; Evidence-Based Practice/methods/*organization & administration ; Humans ; Models, Organizational ; Substance-Related Disorders/*prevention & control ; }, abstract = {The community plays an important role in the success of substance abuse prevention efforts. However, current funding structures and a focus on limited approaches to prevention delivery have created a large gap between what substance abuse prevention professionals practice and what the community at large knows about prevention. The concept of "community" has not always been well-defined in the field of prevention, and there are few mechanisms to engage grassroots community members in evidence-based substance abuse prevention. This article explains how Wandersman et al.'s (Am J Community Psychol 41:171-181, 2008) Interactive Systems Framework can be applied to grassroots prevention efforts. The authors describe a Community Prevention Support System that collaborates with the Professional Prevention Support System to promote the adoption of evidence-based substance abuse prevention practices at the grassroots, community level.}, } @article {pmid22445394, year = {2012}, author = {Kumar, M and Yadav, SP}, title = {The weakest t-norm based intuitionistic fuzzy fault-tree analysis to evaluate system reliability.}, journal = {ISA transactions}, volume = {51}, number = {4}, pages = {531-538}, doi = {10.1016/j.isatra.2012.01.004}, pmid = {22445394}, issn = {1879-2022}, mesh = {*Artificial Intelligence ; Computer Simulation ; Equipment Failure Analysis/*methods ; *Fuzzy Logic ; *Models, Theoretical ; Robotics/*methods ; }, abstract = {In this paper, a new approach of intuitionistic fuzzy fault-tree analysis is proposed to evaluate system reliability and to find the most critical system component that affects the system reliability. Here weakest t-norm based intuitionistic fuzzy fault tree analysis is presented to calculate fault interval of system components from integrating expert's knowledge and experience in terms of providing the possibility of failure of bottom events. It applies fault-tree analysis, α-cut of intuitionistic fuzzy set and T(ω) (the weakest t-norm) based arithmetic operations on triangular intuitionistic fuzzy sets to obtain fault interval and reliability interval of the system. This paper also modifies Tanaka et al.'s fuzzy fault-tree definition. In numerical verification, a malfunction of weapon system "automatic gun" is presented as a numerical example. The result of the proposed method is compared with the listing approaches of reliability analysis methods.}, } @article {pmid22442922, year = {2011}, author = {Lazzeri, G and Pammolli, A and Simi, R and Pilato, V and Giacchi, MV}, title = {BMI from nutritional surveillance of 8-9 years old children in Tuscany (Italy).}, journal = {Journal of preventive medicine and hygiene}, volume = {52}, number = {4}, pages = {181-185}, pmid = {22442922}, issn = {1121-2233}, mesh = {*Body Mass Index ; Child ; Cross-Sectional Studies ; Female ; Humans ; Italy/epidemiology ; Male ; Nutrition Surveys ; Nutritional Status ; Obesity/*epidemiology ; Overweight/*epidemiology ; Population ; Prevalence ; Thinness/*epidemiology ; }, abstract = {INTRODUCTION: The latest increase in childhood obesity focused attention on the important consequences that this phenomenon may have on public health in relationship to the increasing risk that an obese child may become an obese adult. To deal with this problem, there is necessary to assess systematically the distribution of childhood nutritional status at different levels: international, regional and local. In this paper are presented data on underweight, overweight and obesity prevalence in third grade primary school children, aged 8/9 years in Tuscany (2008) and its distribution in relationship to the demographic breadth of their place of residence.

METHODS: Data from statistic sample of 2109 (1.091 males, 1.018 females), 8/9 years school-children were collected; weight and height were measured using standardised personnel and instruments. Exact month age was calculated between the data of measurement and that of birth. Body Mass Index (BMI) classes were calculated using Cole et al.'s epidemiologic cut-off for children and adolescents. Residence areas were divided into four classes based on the number of inhabitants (< 10.000; 10.000-50.000; > 50.000; > 50.000 metropolitan).

RESULTS: The prevalence of underweight was 0.88% (0.76% in males and 1.01% in females), the prevalence of overweight was 23.43% (22.33% in males and 24.65% in females), the prevalence of obese was 7.95% (9.08% in males, 6.70% in females). The lowest prevalence of obese (6.46%) was found in towns with over 50.000 residents (metropolitan).

CONCLUSION: The obesity prevalence in Tuscany children is still lower than that of the Italian National Survey, while the overweight prevalence it's the same. Obesity prevalence (10.71%) is higher in municipalities with low residents number (< 10.000).}, } @article {pmid22433762, year = {2012}, author = {Pickard, AS and Ray, S and Ganguli, A and Cella, D}, title = {Comparison of FACT- and EQ-5D-based utility scores in cancer.}, journal = {Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research}, volume = {15}, number = {2}, pages = {305-311}, doi = {10.1016/j.jval.2011.11.029}, pmid = {22433762}, issn = {1524-4733}, mesh = {Adaptation, Psychological ; Adult ; Aged ; Algorithms ; Cross-Sectional Studies ; Female ; *Health Status ; Humans ; Male ; Middle Aged ; Models, Statistical ; Neoplasms/physiopathology/*psychology ; Patient Preference/psychology/statistics & numerical data ; Patients/*psychology ; Quality of Life/*psychology ; Quality-Adjusted Life Years ; Retrospective Studies ; *Surveys and Questionnaires ; United States ; }, abstract = {OBJECTIVE: Although utility-based algorithms have been developed for the Functional Assessment of Cancer Therapy (FACT), their properties are not well known compared with those of generic utility measures such as the EQ-5D. Our objective was to compare EQ-5D and FACT preference-based scores in cancer patients.

METHODS: A retrospective analysis was conducted on cross-sectional data collected from 472 cancer patients who completed both FACT-General and the EQ-5D. Preference-based scores were calculated by using published scoring functions for the EQ-5D (Dolan P. Modeling valuations for EuroQol health states. Med Care 1997;35:1095-108; Shaw JW, Johnson JA, Coons SJ. US valuation of the EQ-5D health states: development and testing of the D1 valuation model. Med Care 2005;43:203-20) and FACT (Dobrez D, Cella D, Pickard AS, et al. Estimation of patient preference-based utility weights from the Functional Assessment of Cancer Therapy-General. Value Health 2007;10:266-72; Kind P, Macran S. Eliciting social preference weights for Functional Assessment of Cancer Therapy-Lung health states. Pharmacoeconomics 2005;23:1143-53; Cheung YB, Thumboo J, Gao F, et al. Mapping the English and Chinese versions of the Functional Assessment of Cancer Therapy-General to the EQ-5D utility index. Value Health 2009;12:371-6). Scores were compared on the basis of clinical severity by using Eastern Cooperative Oncology Group performance status ratings by physicians and patients. Relative efficiency of each scoring function was examined by using ratios of F statistics.

RESULTS: Mean scores for the overall cohort were lowest when using Kind and Macran's FACT UK societal algorithm (0.55, SD 0.09) and highest when using Dobrez et al.'s FACT US patient algorithm (0.83, SD 0.08). Mean difference scores associated with clinical severity, when extrapolated to quality-adjusted life-years (QALYs), had a range of 0.18 QALYs gained using FACT (Kind and Macran) to 0.45 QALYs gained using the EQ-5D (Dolan). However, relative efficiencies suggested that FACT (Kind and Macran) scores may provide greater statistical power to detect significant differences based on clinical severity.

CONCLUSIONS: We found important differences in utilities scores estimated by each algorithm, with FACT-based algorithms tending to underestimate the QALY benefit compared with algorithms based on the EQ-5D. These differences highlight some of the challenges in using disease-specific preference-based measures for decision making despite potentially more relevant disease-specific content.}, } @article {pmid22433169, year = {2012}, author = {Huedo-Medina, TB and Johnson, BT and Kirsch, I}, title = {Kirsch et al.'s (2008) calculations are correct: reconsidering Fountoulakis & Möller's re-analysis of the Kirsch data.}, journal = {The international journal of neuropsychopharmacology}, volume = {15}, number = {8}, pages = {1193-1198}, doi = {10.1017/S1461145711001878}, pmid = {22433169}, issn = {1469-5111}, mesh = {Antidepressive Agents/*therapeutic use ; Depression/*drug therapy ; Depressive Disorder/*drug therapy ; Depressive Disorder, Major/*drug therapy ; Humans ; }, } @article {pmid22425778, year = {2012}, author = {Bird, GD and Lauwereyns, J and Crawford, MT}, title = {The role of eye movements in decision making and the prospect of exposure effects.}, journal = {Vision research}, volume = {60}, number = {}, pages = {16-21}, doi = {10.1016/j.visres.2012.02.014}, pmid = {22425778}, issn = {1878-5646}, mesh = {Analysis of Variance ; Attention/physiology ; Decision Making/*physiology ; Esthetics/psychology ; Eye Movements/*physiology ; Face ; Female ; Humans ; Male ; Photic Stimulation/methods ; Reaction Time ; Time Factors ; }, abstract = {The aim of the current study was to follow on from previous findings that eye movements can have a causal influence on preference formation. Shimojo et al. (2003) previously found that faces that were presented for a longer duration in a two alternative forced choice task were more likely to be judged as more attractive. This effect only occurred when an eye movement was made towards the faces (with no effect when faces were centrally presented). The current study replicated Shimojo et al.'s (2003) design, whilst controlling for potential inter-stimuli interference in central presentations. As per previous findings, when eye movements were made towards the stimuli, faces that were presented for longer durations were preferred. However, faces that were centrally presented (thus not requiring an eye movement) were also preferred in the current study. The presence of an exposure duration effect for centrally presented faces casts doubt on the necessity of the eye movement in this decision making process and has implications for decision theories that place an emphasis on the role of eye movements in decision making.}, } @article {pmid22413221, year = {2011}, author = {Chen, XL and Xu, CS and Liu, YX and Liang, SL and Qiao, HQ and Xu, HT and Ning, YH and Liu, YC}, title = {Visible luminescence mechanism of ZnO nanoparticles synthesized by sol-gel method.}, journal = {Journal of nanoscience and nanotechnology}, volume = {11}, number = {11}, pages = {9415-9420}, doi = {10.1166/jnn.2011.5290}, pmid = {22413221}, issn = {1533-4880}, abstract = {We presented our investigations on the absorption and emission properties of the nanocrystalline ZnO particles of different particle sizes (2 nm-5 nm) by sol-gel method. In the room temperature PL spectra, three emission bands, ultraviolet (UV), blue and green were observed. With increasing the particle sizes, both the UV and the visible emission bands shifted to lower energies progressively. From the size-dependency, there was a linear relationship between the energetic maxima of the UV and the green emission bands with a slope of about 0.26, which indicated that the green luminescence of ZnO was produced by the transitions of electrons from deep level to the valence band (or shallow acceptor level). A linear dependence was also found between the energetic maxima of the UV and the blue emissions with a slope of 0.15, the origin this blue emission band is not clear at present. While in van Dijken et al.'s paper, however, they identified only two emission bands in the emission spectra, an UV and a broad visible emission band, and the linear fit between the energetic maxima of these two bands in particles of different sizes has a slope of 0.6, so they proposed that the visible emission in ZnO was originated from the recombination of a shallowly trapped electron with a deeply trapped hole. We attributed this divergence to the fact that the broad visible band is actually composed of two separate emission bands originated from two different recombination processes, and should not had been treated as one emission band.}, } @article {pmid22407509, year = {2012}, author = {Bergin, JL and Wade, TD}, title = {A cross-sectional analysis of the cognitive model of bulimia nervosa.}, journal = {The International journal of eating disorders}, volume = {45}, number = {6}, pages = {776-786}, doi = {10.1002/eat.22012}, pmid = {22407509}, issn = {1098-108X}, mesh = {Adolescent ; Adult ; Aged ; Attitude to Health ; Bulimia Nervosa/*psychology ; *Cognition ; Cross-Sectional Studies ; Emotions ; Female ; Forecasting ; Humans ; Middle Aged ; *Models, Psychological ; Self Concept ; Young Adult ; }, abstract = {OBJECTIVE: The present study aimed to directly test Cooper et al.'s cognitive model of the maintenance of bulimia nervosa.

METHOD: The major predictions of the model were tested cross-sectionally using multiple regression analyses and structural equation modeling in a mixed sample comprising nonclinical female university students (n = 298) and clinical eating disorder patients (n = 44).

RESULTS: Consistent with model, negative self-beliefs was associated with negative emotion, negative emotion with positive and negative beliefs about eating, beliefs about eating with eating behavior, and binge eating with negative self-beliefs. However, contrary to hypotheses, results did not consistently support a direct link between compensatory behavior and negative self-beliefs. Furthermore, the role of permissive thoughts was found to be questionable. Of note, results suggested that components of the model may operate to maintain bulimic pathology in a slightly different way for purging and nonpurging behaviors.

DISCUSSION: While the results of this research provide some preliminary evidence for the validity of the cognitive model as an explanation of the persistence of bulimic symptoms, further work is required to develop the model.}, } @article {pmid22407399, year = {2012}, author = {Hsu, CL and Lu, CF}, title = {A security and privacy preserving e-prescription system based on smart cards.}, journal = {Journal of medical systems}, volume = {36}, number = {6}, pages = {3637-3647}, pmid = {22407399}, issn = {0148-5598}, mesh = {*Algorithms ; Computer Security/*instrumentation ; *Confidentiality ; *Electronic Prescribing ; Humans ; Insurance, Pharmaceutical Services ; Patient Identification Systems/methods ; Proxy ; }, abstract = {In 2002, Ateniese and Medeiros proposed an e-prescription system, in which the patient can store e-prescription and related information using smart card. Latter, Yang et al. proposed a novel smart-card based e-prescription system based on Ateniese and Medeiros's system in 2004. Yang et al. considered the privacy issues of prescription data and adopted the concept of a group signature to provide patient's privacy protection. To make the e-prescription system more realistic, they further applied a proxy signature to allow a patient to delegate his signing capability to other people. This paper proposed a novel security and privacy preserving e-prescription system model based on smart cards. A new role, chemist, is included in the system model for settling the medicine dispute. We further presented a concrete identity-based (ID-based) group signature scheme and an ID-based proxy signature scheme to realize the proposed model. Main property of an ID-based system is that public key is simple user's identity and can be verified without extra public key certificates. Our ID-based group signature scheme can allow doctors to sign e-prescription anonymously. In a case of a medical dispute, identities of the doctors can be identified. The proposed ID-based proxy signature scheme can improve signing delegation and allows a delegation chain. The proposed e-prescription system based on our proposed two cryptographic schemes is more practical and efficient than Yang et al.'s system in terms of security, communication overheads, computational costs, practical considerations.}, } @article {pmid22402279, year = {2012}, author = {Cardeña, E and Marcusson-Clavertz, D}, title = {On the need to compare anomalous experiences carefully: commentary on Milán et al.'s Auras in mysticism and synaesthesia: a comparison.}, journal = {Consciousness and cognition}, volume = {21}, number = {2}, pages = {1068-1069}, doi = {10.1016/j.concog.2012.02.003}, pmid = {22402279}, issn = {1090-2376}, mesh = {*Color Perception ; Female ; Humans ; Male ; *Mysticism ; *Parapsychology ; *Perceptual Distortion ; *Social Perception ; }, } @article {pmid22390322, year = {2012}, author = {Oppenheim, GM}, title = {The case for subphonemic attenuation in inner speech: comment on Corley, Brocklehurst, and Moat (2011).}, journal = {Journal of experimental psychology. Learning, memory, and cognition}, volume = {38}, number = {2}, pages = {502-512}, pmid = {22390322}, issn = {1939-1285}, support = {F32 DC000191/DC/NIDCD NIH HHS/United States ; HD44458/HD/NICHD NIH HHS/United States ; R01 DC000191/DC/NIDCD NIH HHS/United States ; DC000191/DC/NIDCD NIH HHS/United States ; R01 HD044458/HD/NICHD NIH HHS/United States ; K23 DC000191/DC/NIDCD NIH HHS/United States ; }, mesh = {*Bias ; Female ; Humans ; Male ; *Psycholinguistics ; Speech/*physiology ; *Thinking ; *Verbal Behavior ; }, abstract = {Corley, Brocklehurst, and Moat (2011) recently demonstrated a phonemic similarity effect for phonological errors in inner speech, claiming that it contradicted Oppenheim and Dell's (2008) characterization of inner speech as lacking subphonemic detail (e.g., features). However, finding an effect in both inner and overt speech is not the same as finding equal effects in inner and overt speech. In this response, I demonstrate that Corley et al.'s data are entirely consistent with the notion that inner speech lacks subphonemic detail and that each of their experiments exhibits a Similarity × Articulation interaction of about the same size that Oppenheim and Dell (2008, 2010) reported in their work. I further show that the major discrepancy between the labs' data lies primarily in the magnitude of the main effect of phonemic similarity and the overall efficiency of error elicitation, and demonstrate that greater similarity effects are associated with lower error rates. This leads to the conclusion that successful speech error research requires finding a sweet spot between too much randomness and not enough data.}, } @article {pmid22388801, year = {2011}, author = {Mattison, SM}, title = {Evolutionary contributions to solving the "matrilineal puzzle": a test of Holden, Sear, and Mace's model.}, journal = {Human nature (Hawthorne, N.Y.)}, volume = {22}, number = {1-2}, pages = {64-88}, pmid = {22388801}, issn = {1936-4776}, mesh = {Adolescent ; Adult ; Age Factors ; Aged ; Aged, 80 and over ; Anthropology, Cultural ; Child ; Child, Preschool ; China ; Cooperative Behavior ; *Cultural Evolution ; Family Characteristics/*ethnology ; Family Relations/*ethnology ; Female ; Gender Identity ; Humans ; Male ; Middle Aged ; Models, Theoretical ; Reproductive Behavior ; Sex Factors ; Socioeconomic Factors ; Young Adult ; }, abstract = {Matriliny has long been debated by anthropologists positing either its primitive or its puzzling nature. More recently, evolutionary anthropologists have attempted to recast matriliny as an adaptive solution to modern social and ecological environments, tying together much of what was known to be associated with matriliny. This paper briefly reviews the major anthropological currents in studies of matriliny and discusses the contribution of evolutionary anthropology to this body of literature. It discusses the utility of an evolutionary framework in the context of the first independent test of Holden et al.'s 2003 model of matriliny as daughter-biased investment. It finds that historical daughter-biased transmission of land among the Mosuo is consistent with the model, whereas current income transmission is not. In both cases, resources had equivalent impacts on male and female reproduction, a result which predicts daughter-biased resource transmission given any nonzero level of paternity uncertainty. However, whereas land was transmitted traditionally to daughters, income today is invested in both sexes. Possible reasons for this discrepancy are discussed.}, } @article {pmid22385306, year = {2012}, author = {Wodrich, MD and Corminboeuf, C and Wheeler, SE}, title = {Accurate thermochemistry of hydrocarbon radicals via an extended generalized bond separation reaction scheme.}, journal = {The journal of physical chemistry. A}, volume = {116}, number = {13}, pages = {3436-3447}, doi = {10.1021/jp212209q}, pmid = {22385306}, issn = {1520-5215}, abstract = {Detailed knowledge of hydrocarbon radical thermochemistry is critical for understanding diverse chemical phenomena, ranging from combustion processes to organic reaction mechanisms. Unfortunately, experimental thermochemical data for many radical species tend to have large errors or are lacking entirely. Here we develop procedures for deriving high-quality thermochemical data for hydrocarbon radicals by extending Wheeler et al.'s "generalized bond separation reaction" (GBSR) scheme (J. Am. Chem. Soc., 2009, 131, 2547). Moreover, we show that the existing definition of hyperhomodesmotic reactions is flawed. This is because transformation reactions, in which one molecule each from the predefined sets of products and reactants can be converted to a different product and reactant molecule, are currently allowed. This problem is corrected via a refined definition of hyperhomodesmotic reactions in which there are equal numbers of carbon-carbon bond types inclusive of carbon hybridization and number of hydrogens attached. Ab initio and density functional theory (DFT) computations using the expanded GBSRs are applied to a newly derived test set of 27 hydrocarbon radicals (HCR27). Greatly reduced errors in computed reaction enthalpies are seen for hyperhomodesmotic and other highly balanced reactions classes, which benefit from increased matching of hybridization and bonding requirements. The best performing DFT methods for hyperhomodesmotic reactions, M06-2X and B97-dDsC, give average deviations from benchmark computations of only 0.31 and 0.44 (±0.90 and ±1.56 at the 95% confidence level) kcal/mol, respectively, over the test set. By exploiting the high degree of error cancellation provided by hyperhomodesmotic reactions, accurate thermochemical data for hydrocarbon radicals (e.g., enthalpies of formation) can be computed using relatively inexpensive computational methods.}, } @article {pmid22374237, year = {2012}, author = {Wei, J and Hu, X and Liu, W}, title = {An improved authentication scheme for telecare medicine information systems.}, journal = {Journal of medical systems}, volume = {36}, number = {6}, pages = {3597-3604}, pmid = {22374237}, issn = {0148-5598}, mesh = {Access to Information ; Computer Security/*standards ; Humans ; *Quality Improvement ; Telemedicine/*methods/standards ; }, abstract = {The telecare medicine information system enables or supports health-care delivery services. In order to safeguard patients' privacy, such as telephone number, medical record number, health information, etc., a secure authentication scheme will thus be in demand. Recently, Wu et al. proposed a smart card based password authentication scheme for the telecare medicine information system. Later, He et al. pointed out that Wu et al.'s scheme could not resist impersonation attacks and insider attacks, and then presented a new scheme. In this paper, we show that both of them fail to achieve two-factor authentication as smart card based password authentication schemes should achieve. We also propose an improved authentication scheme for the telecare medicine information system, and demonstrate that the improved one satisfies the security requirements of two-factor authentication and is also efficient.}, } @article {pmid22372384, year = {2012}, author = {Hurst, CV}, title = {Morphoscopic trait expressions used to identify Southwest Hispanics.}, journal = {Journal of forensic sciences}, volume = {57}, number = {4}, pages = {859-865}, doi = {10.1111/j.1556-4029.2012.02080.x}, pmid = {22372384}, issn = {1556-4029}, mesh = {Black People ; Discriminant Analysis ; Emigrants and Immigrants ; Facial Bones/*anatomy & histology ; Female ; Forensic Anthropology ; *Hispanic or Latino ; Humans ; Latin America/ethnology ; Male ; Mexico/ethnology ; Palate/anatomy & histology ; Southwestern United States ; White People ; Black or African American ; }, abstract = {Hispanics represent the largest and fastest growing minority in the United States. It is increasingly important to understand the skeletal morphology and regional variation within this diverse group. This research focuses on the eight cranial morphoscopic traits of Southwest Hispanics from Birkby et al. (J Forensic Sci 2008;53(1):29-33) and 18 additional traits. Frequency distributions assessed the prevalence of trait expressions in Southwest Hispanic, African-American, and European-American samples. Forward stepwise discriminant function analysis indicated the best traits for differentiating these three groups. Six of the Birkby et al.'s traits are prevalent in the Southwest Hispanic sample and the best traits to distinguish the three groups are as follows: incisor shoveling, anterior malar projection, nasal sill, oval window visualization, enamel extensions, anterior nasal spine, nasal aperture width, and alveolar prognathism. This research demonstrates the efficacy of morphoscopic traits in ancestry determinations and the utility of the aforementioned traits in discriminating Southwest Hispanics, African Americans, and European Americans.}, } @article {pmid22369574, year = {2012}, author = {Kaklamanou, D and Armitage, CJ}, title = {Testing compensatory health beliefs in a UK population.}, journal = {Psychology & health}, volume = {27}, number = {9}, pages = {1062-1074}, doi = {10.1080/08870446.2012.662974}, pmid = {22369574}, issn = {1476-8321}, mesh = {Adolescent ; Adult ; Aged ; Alcohol Drinking/adverse effects/psychology ; *Attitude to Health ; Cross-Cultural Comparison ; *Culture ; Exercise/psychology ; Female ; Follow-Up Studies ; Food Preferences/psychology ; Fruit ; *Health Behavior ; Humans ; Internet ; Male ; Middle Aged ; Psychometrics/statistics & numerical data ; Reproducibility of Results ; *Risk-Taking ; Smoking/adverse effects/psychology ; *Surveys and Questionnaires ; United Kingdom ; Vegetables ; Young Adult ; }, abstract = {Compensatory health beliefs, beliefs that healthy behaviours can compensate or neutralise unhealthy behaviours, have been proposed as one way of understanding why people engage in health-risk behaviours (Knäuper, B., Rabiau, M., Cohen, O., & Patriciu, N. (2004). Compensatory health beliefs scale development and psychometric properties. Psychology and Health, 19, 607-624). However, measuring compensatory health beliefs has proved a challenge, with several recent studies being unable to replicate the psychometric properties of Knäuper et al.'s (2004) scales. The aims of this study were to: (1) test the factor structure of the compensatory health beliefs scale in the UK, (2) examine the predictive validity of the scale by testing the relationships between compensatory health beliefs and health behaviours over a six-month time interval and (3) assess the 6-month test-retest reliability of the scale. A total of 393 participants completed measures of compensatory health beliefs and health behaviours at two time points separated by six months. The findings were potentially problematic for research into compensatory health beliefs: the factor structure was not confirmed, there was little evidence of predictive validity, and test-retest reliability was poor. Further research is required to understand the operation of compensatory health beliefs and to develop the measurement of compensatory health beliefs.}, } @article {pmid22369196, year = {2012}, author = {Miller, J and Knott, VE and Wilson, C and Roder, D}, title = {A review of community engagement in cancer control studies among Indigenous people of Australia, New Zealand, Canada and the USA.}, journal = {European journal of cancer care}, volume = {21}, number = {3}, pages = {283-295}, doi = {10.1111/j.1365-2354.2012.01325.x}, pmid = {22369196}, issn = {1365-2354}, mesh = {Australia ; *Biomedical Research ; Canada ; *Community Participation ; *Health Services, Indigenous ; Humans ; Neoplasms/*therapy ; New Zealand ; United States ; }, abstract = {This review aimed to address studies of cancer control in Indigenous populations, with a focus on: (1) the nature and extent of community engagement; and (2) the extent to which community engagement has facilitated successful outcomes. Articles addressing Indigenous cancer control using some degree of community engagement were identified by a search of the following electronic databases: MEDLINE (via Ovid and Pubmed), psycINFO, CINAHL and Google Scholar. Relevant studies were scored and analysed according to Green et al.'s guidelines for participatory research. Studies often engaged the community only minimally. Where studies resulted in successful outcomes, they tended to have included Indigenous community members in genuine research roles, from planning, to implementation, to presentation of results at conferences. Studies with positive health outcomes were often initiated by a combination of academic researchers and community members or organisations. This narrative review highlighted significant scope for improvement in community-based studies addressing Indigenous cancer control. Increased attention to the philosophical underpinnings of community engagement is required to ensure that the benefits of this approach are translated to achieve improved cancer control outcomes. An increased awareness of the benefits of community engagement may prove effective in conducting cancer control research that leads to improved outcomes in Indigenous communities.}, } @article {pmid22360841, year = {2012}, author = {Hudon, C and Fortin, M and Haggerty, J and Loignon, C and Lambert, M and Poitras, ME}, title = {Patient-centered care in chronic disease management: a thematic analysis of the literature in family medicine.}, journal = {Patient education and counseling}, volume = {88}, number = {2}, pages = {170-176}, doi = {10.1016/j.pec.2012.01.009}, pmid = {22360841}, issn = {1873-5134}, mesh = {Chronic Disease/*therapy ; *Disease Management ; Family Practice/*organization & administration ; Female ; Humans ; Patient Advocacy ; Patient Participation ; *Patient-Centered Care ; Physician's Role ; Physician-Patient Relations ; }, abstract = {OBJECTIVE: The objective was to provide a synthesis of the results of the research and discourse lines on main dimensions of patient-centered care in the context of chronic disease management in family medicine, building on Stewart et al.'s model.

METHODS: We developed search strategies for the Medline, Embase, and Cochrane databases, from 1980 to April 2009. All articles addressing patient-centered care in the context of chronic disease management in family medicine were included. A thematic analysis was performed using mixed codification, based on Stewart's model of patient-centered care.

RESULTS: Thirty-two articles were included. Six major themes emerged: (1) starting from the patient's situation; (2) legitimizing the illness experience; (3) acknowledging the patient's expertise; (4) offering realistic hope; (5) developing an ongoing partnership; (6) providing advocacy for the patient in the health care system.

CONCLUSION: The context of chronic disease management brings forward new dimensions of patient-centered care such as legitimizing the illness experience, acknowledging patient expertise, offering hope and providing advocacy.

PRACTICE IMPLICATIONS: Chronic disease management calls for the adaptation of the family physician's role to patients' fluctuating needs. Literature also suggests the involvement of the family physician in care transitions as a component of patient-centered care.}, } @article {pmid22360421, year = {2012}, author = {Duan, C and Hill, C and Jiang, G and Hu, B and Chui, H and Hui, K and Liu, J and Yu, L}, title = {Therapist directives: use and outcomes in China.}, journal = {Psychotherapy research : journal of the Society for Psychotherapy Research}, volume = {22}, number = {4}, pages = {442-457}, doi = {10.1080/10503307.2012.664292}, pmid = {22360421}, issn = {1468-4381}, mesh = {Adolescent ; Adult ; China ; Directive Counseling/methods/*statistics & numerical data ; Female ; Humans ; Male ; Mental Disorders/*therapy ; Patient Compliance/*statistics & numerical data ; Patient Satisfaction ; Process Assessment, Health Care ; *Professional-Patient Relations ; Psychotherapy/methods/*statistics & numerical data ; Treatment Outcome ; }, abstract = {We examined relationships among the use of therapist directives, client implementation of directives, and outcome for 43 Chinese therapists and their 96 Chinese clients at a university counseling center in mid-China. The results showed that most directives reported by both therapists and clients asked clients to act on or think about intrapersonal or interpersonal issues. Chinese therapists reported giving fewer, but clients reported receiving a similar number of directives than was found in Scheel et al.'s (1999) American sample. Client-rated fit, difficulty, and therapist influence did not predict client implementation directly, nor did implementation predict client-rated outcome directly. Instead, quantity and acceptability of directives interacted in influencing client implementation and use of directives facilitated client-rated outcome through strengthening working alliance.}, } @article {pmid22342280, year = {2012}, author = {Raffard, S and Bayard, S}, title = {Understanding the executive functioning heterogeneity in schizophrenia.}, journal = {Brain and cognition}, volume = {79}, number = {1}, pages = {60-69}, doi = {10.1016/j.bandc.2012.01.008}, pmid = {22342280}, issn = {1090-2147}, mesh = {Adult ; Antipsychotic Agents/therapeutic use ; Brain/physiopathology ; Executive Function/*physiology ; Female ; Humans ; Male ; Middle Aged ; Neuropsychological Tests ; Psychotic Disorders/drug therapy/*physiopathology/psychology ; Schizophrenia/drug therapy/*physiopathology ; *Schizophrenic Psychology ; }, abstract = {Schizophrenia is characterized by heterogeneous brain abnormalities involving cerebral regions implied in the executive functioning. The dysexecutive syndrome is one of the most prominent and functionally cognitive features of schizophrenia. Nevertheless, it is not clear to what extend executive deficits are heterogeneous in schizophrenia patients. Furthermore, it is still unknown if the executive impairments observed in schizophrenia are better characterized as specific or as reflecting generalized cognitive factors. The four executive processes (i.e. updating, inhibition, shifting and divided attention) described in Miyake et al.'s (2000) theoretical model were examined in 62 individuals with schizophrenia and 49 healthy controls. At group level, impairments in all four executive processes confirmed the marked impairment in executive functioning in patients with schizophrenia. Statistical analysis indicated that executive performances in schizophrenia patients were more heterogeneous than in healthy controls. Compared with standardized norms, 94% of patients exhibited impairment in at least one of the executive tasks. Twenty-one percent of patients exhibited impairment in one executive task, 27% in two tasks, 23% in three executive tasks and 23% exhibited impairments in the four executive tasks. Six percent of patients had normal executive profile. Regression analysis indicated that only premorbid intellectual quotient and a general slowing in processing speed predicted the executive dysfunction severity. Executive functioning was not affected by age, duration of illness, psychotic status, or by antipsychotic dosage. Our results emphasize the heterogeneity of the dysexecutive syndrome in schizophrenia when individual profile analysis is considered, and extend the view that individual cognitive differences in schizophrenia are largely underlined by general cognitive factors such as intellectual level and general processing speed.}, } @article {pmid22332748, year = {2012}, author = {Szabó, L and Siegler, Z and Zubek, L and Liptai, Z and Körhegyi, I and Bánsági, B and Fogarasi, A}, title = {A detailed semiologic analysis of childhood psychogenic nonepileptic seizures.}, journal = {Epilepsia}, volume = {53}, number = {3}, pages = {565-570}, doi = {10.1111/j.1528-1167.2012.03404.x}, pmid = {22332748}, issn = {1528-1167}, mesh = {Adolescent ; Child ; Cohort Studies ; Conversion Disorder/*diagnosis/psychology ; Electroencephalography/*methods ; Epilepsy/classification/*diagnosis ; Female ; Humans ; Male ; Retrospective Studies ; Video Recording/*methods ; }, abstract = {PURPOSE: Psychogenic nonepileptic seizure (PNES) is an important differential diagnostic problem in patients with or without epilepsy. There are many studies that have analyzed PNES in adults; currently, however, there is no systematic assessment of purely childhood PNES semiology. Our study based on a large pediatric video-electroencephalography (EEG) monitoring (VEM) cohort, provides a detailed analysis of childhood PNES and assesses the usability of the current classification system described in adults.

METHODS: Medical and video-EEG records of 568 consecutive children (younger than 18 years) who underwent video-EEG monitoring (VEM) at our hospital were reviewed. Aura, type of movement, anatomic distribution, synchrony, symmetry, eye movement, responsiveness, vocalization, hyperventilation, vegetative and emotional signs, presence of eyewitness, and duration of the event were recorded among children with the diagnosis of PNES. We also compared our data with those of earlier adult studies.

KEY FINDINGS: Seventy-five archived PNES of 27 children (21 girls; age 8-18 years) were reanalyzed. Nine children (33%) had the diagnosis of epilepsy currently or in the past. Mean age at the time of PNES onset was 11.6 (standard deviation 3.2) years. Mean duration of PNES was longer (269 s) compared to seizures of the epileptic group (83 s; p = 0.002). Eyewitnesses (mostly parents) were present in 89% of cases. Eighty percent of PNES had an abrupt start, with 68% also ending abruptly. In only 15% of events were the patients eyes closed at the beginning of the attack. Patients were unresponsive in 34%. The most frequent motor sign was tremor (25%) with the upper, rather than lower limbs more frequently involved. Pelvic thrusting was seen in only two attacks. Emotional-mostly negative-signs were observed during 32 PNES (43%). Based on Seneviratne et al.'s classification, 18 events (24%) were classified as rhythmic motor PNES, only half the frequency of that previously described in adults. No hypermotor PNES was found. The frequency of complex motor PNES (13%) and mixed PNES (4%) showed similar frequency in children as in adults. Dialeptic PNES was found more frequently among younger children. All PNES belonged to the same semiologic type in 23 patients (85%).

SIGNIFICANCE: Because homogeneity of PNES within a patient was high in the pediatric population, we found it useful to classify PNES into different semiologic categories. Dialeptic PNES seems to be more frequent among younger children. Tremor is the most frequent motor sign and usually accompanied by preserved responsiveness in childhood. Negative emotion is commonly seen in pediatric PNES, but pelvic thrusting is a rare phenomenon. We, therefore, suggest a modification of the present classification system in which PNES with motor activity is divided into minor and major motor PNES, and the latter group is subdivided into synchron rhythmic motor and asynchron motor PNES. We believe that our study, a detailed analysis on the semiology and classification of purely childhood PNES might assist the early and precise diagnosis of nonepileptic paroxysmal events.}, } @article {pmid22331613, year = {2012}, author = {Calce, SE}, title = {A new method to estimate adult age-at-death using the acetabulum.}, journal = {American journal of physical anthropology}, volume = {148}, number = {1}, pages = {11-23}, doi = {10.1002/ajpa.22026}, pmid = {22331613}, issn = {1096-8644}, mesh = {Acetabulum/*anatomy & histology ; Adolescent ; Adult ; Age Determination by Skeleton/*methods ; Aged ; Female ; Humans ; Male ; Middle Aged ; Regression Analysis ; Statistics, Nonparametric ; }, abstract = {Rissech et al. (J Forensic Sci 51 (2006) 213-229) described a method to estimate age-at-death of adult males using seven traits of the fused acetabulum. This study simplifies Rissech et al.'s technique and extends its application to adult females. Rissech et al.'s original scoring method was applied to a sample of 100 known-aged adults, three variables were selected based on stepwise multiple regression, and ages were collapsed into three broad ranges: young adult (17-39 years), middle adult (40-64 years), and old adult (65+ years). The revised method was applied to 249 new known-aged individuals from two other samples. To minimize observer bias, highlight the most critical traits, and encompass more age-related variation, unique digital renderings accompany morphological descriptions of age categories instead of photos. Three statistically significant characteristics highly correlated with age (P < 0.05) are capable of estimating age-at-death with 81% accuracy, both sexes combined. For misidentified individuals the tendency was to underestimate age. Results of both intraobserver error testing and inter-rater reliability demonstrated a moderate to substantial agreement in scoring between observers. When estimating the degree of development of features osteophyte development of the acetabular rim was the most inconsistent between observers. The revised acetabular method shows promise in estimating age for adults, particularly for those over the age of 65 years.}, } @article {pmid22329827, year = {2012}, author = {Merrick, S and Farrell, D}, title = {Head and neck cancer patients' experiences of percutaneous endoscopic gastrostomy feeding: a Q-methodology study.}, journal = {European journal of cancer care}, volume = {21}, number = {4}, pages = {493-504}, doi = {10.1111/j.1365-2354.2012.01326.x}, pmid = {22329827}, issn = {1365-2354}, mesh = {Adult ; Aged ; Enteral Nutrition/*methods ; Factor Analysis, Statistical ; Female ; *Gastrostomy ; Head and Neck Neoplasms/psychology/surgery/*therapy ; Humans ; Male ; Middle Aged ; *Patient Satisfaction ; Quality of Life ; }, abstract = {Head and neck cancer patients are at high risk of malnutrition and its complications and therefore often undergo non-oral nasogastric or percutaneous endoscopic gastrostomy (PEG) nutrition support. However, there is little evidence that either approach is effective in this group. While one possible explanation for these findings relates to the relationship between artificial tube feeding and poor quality of life, there is little research that examines the patient's subjective experience of nutrition support. This study investigated the experiences of PEG tube feeding in head and neck cancer patients undergoing radical treatment. Conventional Q-methodology was used with 15 head and neck cancer patients, who rank-ordered 36 statements according to the extent to which these reflected their experiences of PEG tube feeding. The sorted statements were factor-analysed case-wise to provide clusters of similar experiences. Three perspectives emerged. Factor 1, labelled 'Constructive cognitive appraisal', focused around positive adaptation to, and acceptance of, PEG feeding. Factor 2, labelled 'Cognitive-affective dissonance', reflected ambivalence between cognitive acceptance and affective rejection of the PEG tube. Factor 3, labelled 'Emotion-focused appraisal', was characterised by tube-focused anxiety and fear. The findings broadly confirm Levanthal et al.'s Self-Regulatory Model of coping and support the need for genuine and individualised patient-centred nutritional care.}, } @article {pmid22329789, year = {2012}, author = {Bertels, J and Franco, A and Destrebecqz, A}, title = {How implicit is visual statistical learning?.}, journal = {Journal of experimental psychology. Learning, memory, and cognition}, volume = {38}, number = {5}, pages = {1425-1431}, doi = {10.1037/a0027210}, pmid = {22329789}, issn = {1939-1285}, mesh = {Adolescent ; Adult ; Analysis of Variance ; Choice Behavior/physiology ; Consciousness ; Female ; Humans ; Learning/*physiology ; Male ; *Pattern Recognition, Visual ; Photic Stimulation ; Reaction Time ; *Unconsciousness ; Young Adult ; }, abstract = {In visual statistical learning, participants learn the statistical regularities present in a sequence of visual shapes. A recent study (Kim, Seitz, Feenstra, & Shams, 2009) suggests that visual statistical learning occurs implicitly, as it is not accompanied by conscious awareness of these regularities. However, that interpretation of the data depends on 2 unwarranted assumptions concerning the nature and sensitivity of the tasks used to measure learning. In a replication of this study, we used a 4-choice completion task as a direct measure of learning, in addition to an indirect measure consisting of a rapid serial visual presentation task. Moreover, binary confidence judgments were recorded after each completion trial. This way, we measured systematically the extent to which sequence knowledge was available to consciousness. Supporting the notion that the role of unconscious knowledge was overestimated in Kim et al.'s study, our results reveal that participants' performance cannot be exclusively accounted for by implicit knowledge.}, } @article {pmid22329343, year = {2012}, author = {Tebbe, EN and Moradi, B}, title = {Anti-transgender prejudice: a structural equation model of associated constructs.}, journal = {Journal of counseling psychology}, volume = {59}, number = {2}, pages = {251-261}, doi = {10.1037/a0026990}, pmid = {22329343}, issn = {0022-0167}, mesh = {Adolescent ; Adult ; Female ; *Gender Identity ; *Homosexuality ; Humans ; Male ; Models, Psychological ; Multivariate Analysis ; *Prejudice ; Sex Factors ; Social Desirability ; Social Dominance ; *Transsexualism ; United States ; Young Adult ; }, abstract = {This study aimed to identify theoretically relevant key correlates of anti-transgender prejudice. Specifically, structural equation modeling was used to test the unique relations of anti-lesbian, gay, and bisexual (LGB) prejudice; traditional gender role attitudes; need for closure; and social dominance orientation with anti-transgender prejudice. Social desirability was controlled as a covariate in the model. Analyses of data from 250 undergraduate students indicated that anti-LGB prejudice, traditional gender role attitudes, and need for closure each had positive unique relations with anti-transgender prejudice beyond the negative association of social desirability with such prejudice. By contrast, social dominance orientation was not related uniquely to anti-transgender prejudice. Additional analyses indicated that women's mean level of anti-transgender prejudice was lower than that of men's, but the pattern of relations between the predictor variables and anti-transgender prejudice did not differ between women and men. A confirmatory factor analysis also supported the unidimensional structure of anti-transgender prejudice as operationalized by Nagoshi et al.'s (2008) Transphobia Scale.}, } @article {pmid22324341, year = {2012}, author = {Terada, K and Nakamura, H and Kanaizuka, K and Haga, MA and Asai, Y and Ishida, T}, title = {Long-range electron transport of ruthenium-centered multilayer films via a stepping-stone mechanism.}, journal = {ACS nano}, volume = {6}, number = {3}, pages = {1988-1999}, doi = {10.1021/nn300126m}, pmid = {22324341}, issn = {1936-086X}, mesh = {Electrochemistry ; Electron Transport ; Models, Molecular ; Molecular Conformation ; Ruthenium/*chemistry ; }, abstract = {We studied electron transport of Ru complex multilayer films, whose structure resembles redox-active complex films known in the literature to have long-range electron transport abilities. Hydrogen bond formation in terms of pH control was used to induce spontaneous growth of a Ru complex multilayer. We made a cross-check between electrochemical measurements and I-V measurements using PEDOT:PSS to eliminate the risk of pinhole contributions to the mechanism and have found small β values of 0.012-0.021 Å(-1). Our Ru complex layers exhibit long-range electron transport but with low conductance. On the basis of the results of our theoretical-experimental collaboration, we propose a modified tunneling mechanism named the "stepping-stone mechanism", where the alignment of site potentials forms a narrow band around E(F), making resonant tunneling possible. Our observations may support Tuccito et al.'s proposed mechanism.}, } @article {pmid22296984, year = {2012}, author = {Adrover-Roig, D and Sesé, A and Barceló, F and Palmer, A}, title = {A latent variable approach to executive control in healthy ageing.}, journal = {Brain and cognition}, volume = {78}, number = {3}, pages = {284-299}, doi = {10.1016/j.bandc.2012.01.005}, pmid = {22296984}, issn = {1090-2147}, mesh = {Age Factors ; Aged ; Aged, 80 and over ; Aging/*psychology ; Executive Function/*physiology ; Female ; Humans ; Inhibition, Psychological ; Learning/physiology ; Male ; Memory/physiology ; Middle Aged ; Neuropsychological Tests ; }, abstract = {It is a well-established finding that the central executive is fractionated in at least three separable component processes: Updating, Shifting, and Inhibition of information (Miyake et al., 2000). However, the fractionation of the central executive among the elderly has been less well explored, and Miyake's et al. latent structure has not yet been integrated with other models that propose additional components, such as access to long-term information. Here we administered a battery of classic and newer neuropsychological tests of executive functions to 122 healthy individuals aged between 48 and 91 years. The test scores were subjected to a latent variable analysis (LISREL), and yielded four factors. The factor structure obtained was broadly consistent with Miyake et al.'s three-factor model. However, an additional factor, which was labeled 'efficiency of access to long-term memory', and a mediator factor ('speed of processing') were apparent in our structural equation analysis. Furthermore, the best model that described executive functioning in our sample of healthy elderly adults included a two-factor solution, thus indicating a possible mechanism of dedifferentiation, which involves larger correlations and interdependence of latent variables as a consequence of cognitive ageing. These results are discussed in the light of current models of prefrontal cortex functioning.}, } @article {pmid22261553, year = {2012}, author = {Erbudak, HÖ and Ozbek, M and Uysal, S and Karabulut, E}, title = {Application of Kvaal et al.'s age estimation method to panoramic radiographs from Turkish individuals.}, journal = {Forensic science international}, volume = {219}, number = {1-3}, pages = {141-146}, doi = {10.1016/j.forsciint.2011.12.012}, pmid = {22261553}, issn = {1872-6283}, mesh = {Adolescent ; Adult ; Age Determination by Teeth/*methods ; Dental Pulp/diagnostic imaging/growth & development ; Feasibility Studies ; Female ; Forensic Dentistry ; Humans ; Image Processing, Computer-Assisted ; Linear Models ; Male ; Middle Aged ; *Radiography, Panoramic ; Turkey ; Young Adult ; }, abstract = {Age estimation of living adult individuals can be accomplished with limited methods. Radiographic dental methods based on the pulpal narrowing with secondary dentin formation have been presented. In the present study, Kvaal et al.'s method, one of the radiographic dental age estimation methods, was applied to panoramic radiographs from Turkish individuals. The correlation between chronological and estimated ages was examined and the feasibility of length and width measurements of pulp cavity was evaluated for age estimation. The study population consisted of 123 patients with ages ranging from 14 to 57 years. The measurements of the length and width of six types of teeth on digitized panoramic radiographs were performed, and the ratios between tooth and pulp cavity measurements were calculated. Age was estimated using the linear regression models presented by Kvaal et al. and Paewinsky et al. High differences were observed between chronological and estimated ages. Measurement ratios showed no significant or weak correlation with age. The linear regression models were derived using variables that were significantly correlated with age. The determination coefficients of the models varied from 0.035 to 0.345. In conclusion, a difference of more than 12 years in the chronological and estimated ages derived using regression models in literature was found on panoramic radiographs in Turkish individuals. The length and width of the pulp cavity, measured according to the method of Kvaal et al. using panoramic radiographs, were insufficient to precisely estimate the age of Turkish individuals.}, } @article {pmid22258821, year = {2012}, author = {Augustinova, M and Ferrand, L}, title = {Suggestion does not de-automatize word reading: evidence from the semantically based Stroop task.}, journal = {Psychonomic bulletin & review}, volume = {19}, number = {3}, pages = {521-527}, pmid = {22258821}, issn = {1531-5320}, mesh = {Adult ; Humans ; Neuropsychological Tests ; *Reading ; *Semantics ; *Stroop Test ; Suggestion ; Young Adult ; }, abstract = {Recent studies have shown that the suggestion for participants to construe words as meaningless symbols reduces, or even eliminates, standard Stroop interference in highly suggestible individuals (Raz, Fan, & Posner, 2005; Raz, Kirsch, Pollard, & Nitkin-Kaner, 2006). In these studies, the researchers consequently concluded that this suggestion de-automatizes word reading. The aim of the present study was to closely examine this claim. To this end, highly suggestible individuals completed both standard and semantically based Stroop tasks, either with or without a suggestion to construe the words as meaningless symbols (manipulated in both a between-participants [Exp. 1] and a within-participants [Exp. 2] design). By showing that suggestion substantially reduced standard Stroop interference, these two experiments replicated Raz et al.'s (2006) results. However, in both experiments we also found significant semantically based Stroop effects of similar magnitudes in all suggestion conditions. Taken together, these results indicate that the suggestion to construe words as meaningless symbols does not eliminate, or even reduce, semantic activation (assessed by the semantically based Stroop effect) in highly suggestible individuals, and that such an intervention most likely reduces nonsemantic task-relevant response competition related to the standard Stroop task. In sum, contrary to Raz et al.'s claim, suggestion does not de-automatize or prevent reading (as shown by a significant amount of semantic processing), but rather seems to influence response competition. These results also add to the growing body of evidence showing that semantic activation in the Stroop task is indeed automatic.}, } @article {pmid22250905, year = {2012}, author = {Le Pelley, ME}, title = {Metacognitive monkeys or associative animals? Simple reinforcement learning explains uncertainty in nonhuman animals.}, journal = {Journal of experimental psychology. Learning, memory, and cognition}, volume = {38}, number = {3}, pages = {686-708}, doi = {10.1037/a0026478}, pmid = {22250905}, issn = {1939-1285}, mesh = {Animals ; Association Learning/*physiology ; Choice Behavior/physiology ; Cognition/*physiology ; Computer Simulation ; Feedback, Physiological ; Haplorhini ; Humans ; Models, Psychological ; Perception ; *Reinforcement, Psychology ; *Uncertainty ; }, abstract = {Monkeys will selectively and adaptively learn to avoid the most difficult trials of a perceptual discrimination learning task. Couchman, Coutinho, Beran, and Smith (2010) have recently demonstrated that this pattern of responding does not depend on animals receiving trial-by-trial feedback for their responses; it also obtains if experience of the most difficult trials occurs only under conditions of deferred feedback. Couchman et al. argued that this ruled out accounts based on low-level processes of associative learning and instead required explanation in terms of metacognitive processes of decision monitoring. Contrary to this argument, a simple associative model of reinforcement learning is shown to account for the key findings of Couchman et al.'s empirical study, along with several other findings that have previously been claimed to challenge associative models.}, } @article {pmid22231606, year = {2012}, author = {Chen, J and Proctor, RW}, title = {Influence of category identity on letter matching: conceptual penetration of visual processing or response competition?.}, journal = {Attention, perception & psychophysics}, volume = {74}, number = {4}, pages = {716-729}, doi = {10.3758/s13414-011-0264-x}, pmid = {22231606}, issn = {1943-393X}, mesh = {*Association Learning ; *Attention ; *Discrimination Learning ; Humans ; Orientation ; *Pattern Recognition, Visual ; Psychomotor Performance ; Reaction Time ; *Size Perception ; }, abstract = {Participants performed same-different matching tasks, with physical-identity instructions, on letter pairs composed from the letters B, b, and p. The letters in a pair were presented simultaneously or sequentially, with the experiments differing in whether (1) the letters could appear in two or four positions, (2) two or five SOAs were used, (3) the font was Arial or one in which the two loops of the letter B were of the same size, and (4) p did or did not occur in same pairs. With sequential presentation, different RTs were longer when the letters had the same name (Bb; within-category pair) than when they did not (Bp; between-category pair), replicating a finding by Lupyan et al. (2010). However, unlike in their study, this category effect was also significant with simultaneous presentation, tending to be nonsignificantly smaller for RTs but larger for accuracy than that obtained with sequential presentation. A similar pattern was observed when we removed a bias to respond different whenever the letter p was detected in the experiments in which p did not appear in same pairs. The presence of a category effect with simultaneous presentation is predicted by a response competition account, but not by Lupyan et al.'s conceptual-penetration-of-visual-processing account.}, } @article {pmid23870184, year = {2012}, author = {Moran, M and Ortega, J and Hodoglugil, NN}, title = {Osur et al.'s Implementation of misoprostol for postabortion care in Kenya and Uganda: a qualitative evaluation.}, journal = {Global health action}, volume = {6}, number = {}, pages = {21786}, pmid = {23870184}, issn = {1654-9880}, mesh = {Abortifacient Agents/*administration & dosage ; Aftercare/*methods ; *Clinical Protocols ; Female ; Humans ; Misoprostol/*administration & dosage ; Pregnancy ; }, } @article {pmid22202589, year = {2011}, author = {Egilman, DS and Ardolino, EL and Howe, S and Bird, T}, title = {Deconstructing a state-of-the-art review of the asbestos brake industry.}, journal = {New solutions : a journal of environmental and occupational health policy : NS}, volume = {21}, number = {4}, pages = {545-571}, doi = {10.2190/NS.21.4.e}, pmid = {22202589}, issn = {1541-3772}, mesh = {*Asbestos/adverse effects ; *Bias ; *Industry ; Mesothelioma/etiology ; Occupational Exposure/legislation & jurisprudence ; *Review Literature as Topic ; Truth Disclosure ; }, abstract = {State of the art is a legal concept that describes what was known as knowable by experts including manufacturer's state of knowledge about the potential hazards of their product(s) at a point in time. In 2004, Paustenbach et al. published a state-of-the-art review that describes the development of knowledge about asbestos hazards to brake mechanics performing asbestos brake installation and maintenance. Paustenbach et al.'s review, however, omits important pieces of corporate knowledge, dismisses several historical scientific conclusions and ignores the way experts have applied the results of scientific research to protect workers and consumers handling asbestos brakes. By taking their state-of-the-art review out of the legal liability context, Paustenbach et al. create a misleading version of events that fails to properly address the question of what asbestos brake manufacturers knew or should have known about the potential hazards of their brakes to mechanics over time. Without proper presentation of this information, judges and juries cannot adequately assess whether these companies had a duty to warn or take other action to prevent injury to those exposed to their asbestos brakes.}, } @article {pmid22171405, year = {2011}, author = {Razzell, P}, title = {The decline of adult smallpox in eighteenth-century London: a commentary.}, journal = {The Economic history review}, volume = {64}, number = {4}, pages = {1315-1335}, doi = {10.1111/j.1468-0289.2011.00620.x}, pmid = {22171405}, issn = {0013-0117}, mesh = {*Disease Transmission, Infectious/history ; History, 18th Century ; History, 19th Century ; Humans ; London/ethnology ; *Physicians/economics/history/legislation & jurisprudence/psychology ; *Population Groups/education/ethnology/history/legislation & jurisprudence/psychology ; *Preventive Health Services/economics/history/legislation & jurisprudence ; *Smallpox/ethnology/history ; Smallpox Vaccine ; *Social Class/history ; }, abstract = {This article is a response to Davenport, Schwarz, and Boulton's article, ‘The decline of adult smallpox in eighteenth-century London’. It introduces new data on the parish of St Mary Whitechapel which casts doubt on the pattern of the age incidence of smallpox found by Davenport et al. However, it is concluded that there was a decline in adult smallpox in London, accompanied by a concentration of the disease among children under the age of five. Davenport et al.'s argument that the shift in the age incidence was due to the endemicization of smallpox in England is challenged, with an alternative view that these age changes can be accounted for by the practice of inoculation, both in the hinterland southern parishes of England and in London itself. A detailed discussion is carried out on the history of inoculation in London for the period 1760–1812. It is suggested that inoculation became increasingly popular in this period, rivalling in popularity the practice of vaccination. This was associated with a class conflict between the medical supporters of Jenner and the general population, with many of the latter being practitioners of the old inoculation.}, } @article {pmid22164554, year = {2011}, author = {St-Pierre, M and Legault-Mercier, S and Grégoire, L and Côté, L}, title = {[General practitioners in private practice in the city of Quebec and the application of population responsibility].}, journal = {Canadian journal of public health = Revue canadienne de sante publique}, volume = {102}, number = {6}, pages = {437-440}, pmid = {22164554}, issn = {0008-4263}, mesh = {*Attitude of Health Personnel ; General Practitioners/*psychology/standards/trends ; Health Policy/*trends ; Humans ; Interviews as Topic ; Practice Patterns, Physicians'/standards/trends ; Primary Health Care/*standards/trends ; Private Practice ; Qualitative Research ; Quebec ; Social Responsibility ; }, abstract = {Objectives: The aim of this study is to examine the way in which general practitioners (GPs) in private practice view the idea of population responsibility, proposed by the Quebec Health and Social Services Ministry in 2004. We then look at how these views impact primary health care practice in Quebec City. Method: A qualitative exploratory approach was used; 18 semi-directed interviews were performed with private practice GPs, administrators and health professionals from community health and social services centres (CSSS). A content thematic analysis of the data was performed based on St-Pierre et al.’s model and grounded on Giddens’ structuring theory. Results: Because neither the population meant to be served nor the underlying responsibility are perceived the same way by the GPs and the CSSS health professionals, the respective practices do not always converge. Consequently, methods of communication, offers of services and management of resources impact on the operationalization of the concept of population responsibility, which has to be negotiated. Discussion: In these negotiations, because physicians are the ones solicited by the other partners, the application of population responsibility increasingly becomes an opportunity to develop a medically oriented primary care organization.}, } @article {pmid22150361, year = {2012}, author = {Chow, TW and Links, KA and Masterman, DL and Mendez, MF and Vinters, HV}, title = {A case of semantic variant primary progressive aphasia with severe insular atrophy.}, journal = {Neurocase}, volume = {18}, number = {6}, pages = {450-456}, pmid = {22150361}, issn = {1465-3656}, support = {F32 AG022802/AG/NIA NIH HHS/United States ; P50 AG016570/AG/NIA NIH HHS/United States ; }, mesh = {Aphasia, Primary Progressive/*pathology/physiopathology/psychology ; Atrophy ; Autopsy ; Behavioral Symptoms ; Cerebral Cortex/*pathology/physiopathology ; Compulsive Behavior/pathology ; Frontotemporal Dementia/*pathology/physiopathology/psychology ; Humans ; Male ; Middle Aged ; Neuropsychological Tests ; Semantics ; }, abstract = {Insular degeneration has been linked to symptoms of frontotemporal dementia (FTD). Presented in this case is a patient exhibiting semantic variant primary progressive aphasia, behavioral disturbance. Upon autopsy, he was found to have severe insular atrophy. In addition, selective serotonin reuptake inhibitors were ineffective in reducing symptoms of obsessive-compulsive behaviors or emotional blunting. This case suggests that Seeley et al.'s (2007 , Alzheimer Disease & Associated Disorders, 21, S50) hypothesis that von Economo neurons and fork cell-rich brain regions, particularly in the insula, are targeted in additional subtypes of FTD beyond the behavioral variant.}, } @article {pmid22142837, year = {2012}, author = {Sumner, JA}, title = {The mechanisms underlying overgeneral autobiographical memory: an evaluative review of evidence for the CaR-FA-X model.}, journal = {Clinical psychology review}, volume = {32}, number = {1}, pages = {34-48}, pmid = {22142837}, issn = {1873-7811}, support = {F31 MH088014/MH/NIMH NIH HHS/United States ; F31MH088014/MH/NIMH NIH HHS/United States ; }, mesh = {Brain/*physiology ; Executive Function ; Humans ; *Memory, Episodic ; *Models, Psychological ; Psychological Tests ; }, abstract = {Overgeneral autobiographical memory (OGM) has been found to be an important cognitive phenomenon with respect to depression and trauma-related psychopathology (e.g., posttraumatic stress disorder), and researchers have been interested in better understanding the factors that contribute to this proposed vulnerability factor. The most prominent model of mechanisms underlying OGM to date is Williams et al.'s (2007) CaR-FA-X model. This model proposes that three processes influence OGM: capture and rumination, functional avoidance, and impaired executive control. The author reviews the current state of support for the CaR-FA-X model by evaluating 38 studies that have examined OGM and one or more mechanisms of the model. Collectively, these studies reveal robust support for associations between OGM and both rumination and impaired executive control. OGM also appears to be a cognitive avoidance strategy, and there is evidence that avoiding the retrieval of specific memories reduces distress after an aversive event, at least in the short term. Important issues that have been left unresolved are highlighted, including the nature of the capture phenomenon, the role of trauma in functional avoidance, and the developmental nature of functional avoidance. Recommendations for future research that will enhance understanding of the factors that contribute to OGM are suggested.}, } @article {pmid22128663, year = {2011}, author = {Perinetti, G and Contardo, L}, title = {Dr. Giuseppe Perinetti comments on Dr. Nozomi Maeda, et al.'s article (pps. 194-203) in CRANIO's July, 2011 issue.}, journal = {Cranio : the journal of craniomandibular practice}, volume = {29}, number = {4}, pages = {253-4; author reply 254}, pmid = {22128663}, issn = {0886-9634}, mesh = {*Dental Occlusion ; Humans ; *Leg Length Inequality ; *Posture ; }, } @article {pmid22127388, year = {2012}, author = {Liu, R and Dong, HF and Jiang, MS}, title = {What is the role of health education in the integrated strategy to control transmission of Schistosoma japonicum in China?.}, journal = {Parasitology research}, volume = {110}, number = {5}, pages = {2081-2082}, pmid = {22127388}, issn = {1432-1955}, mesh = {Animals ; Cattle ; Cattle Diseases/*epidemiology/*prevention & control ; China/epidemiology ; Communicable Disease Control/*methods ; Health Education/*methods/statistics & numerical data ; Humans ; Schistosoma japonicum/pathogenicity ; Schistosomiasis japonica/epidemiology/*prevention & control/transmission/*veterinary ; Snails/parasitology ; }, abstract = {In 2009, Wang et al.'s field trial published in the New England Journal of Medicine, reported that a comprehensive strategy aiming to reduce the roles of humans and cattle as sources of Schistosoma japonicum infection in snails was implemented and proved effective and promising in dramatically reducing the percentage of infected humans and snails, which had been extended to other endemic provinces in China afterwards. This implies that the integrated schistosomiasis-control strategies of interventions including political will, financial support and residents' participation to control human and bovine sources of S. japonicum infection in snails may direct to successfully interrupt the parasitic transmission and to ultimately eliminate schistosomiasis. Confusingly, however, the role of health education, which is a critical part of the integrated strategy and should play an active role in schistosomiasis control, was not reflected. We wish the authors to provide the readers a better and clearer statement of the role of health education as part of the integrated control strategy and so we write this comment.}, } @article {pmid22105306, year = {2011}, author = {Whitehead, CR and Austin, Z and Hodges, BD}, title = {Intentions versus unintended discursive consequences: reflections upon Sherbino et al.'s commentary on "Flower Power".}, journal = {Advances in health sciences education : theory and practice}, volume = {16}, number = {5}, pages = {699-701}, doi = {10.1007/s10459-011-9337-9}, pmid = {22105306}, issn = {1573-1677}, mesh = {*Clinical Competence ; Competency-Based Education/*organization & administration ; Education, Medical/*methods ; Humans ; *Physician's Role ; }, } @article {pmid22082685, year = {2012}, author = {Canning, SE and Waterman, MG and Simpson, N and Dye, L}, title = {Reliability and component structure of the modified Daily Symptom Report (DSR-20).}, journal = {Journal of affective disorders}, volume = {136}, number = {3}, pages = {612-619}, doi = {10.1016/j.jad.2011.10.021}, pmid = {22082685}, issn = {1573-2517}, mesh = {Adult ; Aggression ; Female ; Follicular Phase/*psychology ; Humans ; Impulsive Behavior ; Luteal Phase/*psychology ; Premenstrual Syndrome/*diagnosis/physiopathology/*psychology ; Reproducibility of Results ; Severity of Illness Index ; }, abstract = {OBJECTIVES: The purpose of the present study was to modify Freeman et al.'s (1996) Daily Symptom Report (DSR) for premenstrual syndrome (PMS) by adding items depicting aggressive and impulsive symptoms, to explore the component structure of this revised measure (DSR-20) in a sample of PMS sufferers, and to compare their scores with those from controls during the follicular and luteal cycle phases.

METHODS: The DSR-20 was administered to 140 PMS sufferers who were seeking treatment for PMS and 54 controls who considered themselves to be free from premenstrual complaints daily for three menstrual cycles.

RESULTS: Cronbach's α was 0.95 for the luteal DSR-20 scores of the PMS sufferers, indicating very high internal consistency of the 20 items. Exploratory Principal Components Analysis (PCA) of the luteal ratings of the PMS sufferers identified two components with high internal consistency (>0.90), describing psychological and physical premenstrual symptoms. PMS sufferers scored significantly higher than the controls on each of these components during the luteal, but not follicular, phase.

CONCLUSIONS: The DSR-20 total scale score is an internally consistent global measure of the intensity of PMS. The division of PMS symptoms into psychological and physical components, both of which significantly differentiated PMS sufferers from controls during the luteal phase, sheds further light on the description of PMS and provides a clinically relevant and practical means by which to summarise and interpret daily symptom ratings, necessary for the identification and investigation of the syndrome.}, } @article {pmid22082213, year = {2012}, author = {Slattery, TJ and Staub, A and Rayner, K}, title = {Saccade launch site as a predictor of fixation durations in reading: comments on Hand, Miellet, O'Donnell, and Sereno (2010).}, journal = {Journal of experimental psychology. Human perception and performance}, volume = {38}, number = {1}, pages = {251-261}, doi = {10.1037/a0025980}, pmid = {22082213}, issn = {1939-1277}, support = {HD 26765/HD/NICHD NIH HHS/United States ; }, mesh = {Analysis of Variance ; *Data Interpretation, Statistical ; Fixation, Ocular/*physiology ; Humans ; Linear Models ; Psycholinguistics/*methods ; *Reading ; Saccades/*physiology ; Time Factors ; }, abstract = {An important question in research on eye movements in reading is whether word frequency and word predictability have additive or interactive effects on fixation durations. A fair number of studies have reported only additive effects of the frequency and predictability of a target word on reading times on that word, failing to show significant interactions. Recently, however, Hand, Miellet, O'Donnell, and Sereno (see record 2010-19099-001) reported interactive effects in a study that included the distance of the prior fixation from the target word (launch site). They reported that when the saccade into the target word was launched from very near to the word (within 3 characters), the predictability effect was larger for low frequency words, but when the saccade was launched from a medium distance (4-6 characters from the word) the predictability effect was larger for high frequency words. Hand et al. argued for the importance of including launch site in analyses of target word fixation durations. Here we describe several problems with Hand et al.'s use of analyses of variance in which launch site is divided into distinct ordinal levels. We describe a more appropriate way to analyze such data-linear mixed-effect models-and we use this method to show that launch site does not modulate the interaction between frequency and predictability in two other data sets.}, } @article {pmid22081276, year = {2012}, author = {Guérard, K and Saint-Aubin, J and Burns, SC and Chamberland, C}, title = {Revisiting backward recall and benchmark memory effects: a reply to Bireta et al. (2010).}, journal = {Memory & cognition}, volume = {40}, number = {3}, pages = {388-407}, pmid = {22081276}, issn = {1532-5946}, mesh = {*Benchmarking ; Humans ; *Memory, Short-Term ; }, abstract = {When participants are asked to recall lists of items in the reverse order, known as backward recall, several benchmark memory phenomena, such as the word length effect, are abolished (Bireta et al. Memory & Cognition 38:279-291, 2010). Bireta et al. (Memory & Cognition 38:279-291, 2010) suggested that in backward recall, reliance on order retention is increased at the expense of item retention, leading to the abolition of item-based phenomena. In a subsequent study, however, Guérard and Saint-Aubin (in press) showed that four lexical factors known to modulate item retention were unaffected by recall direction. In a series of five experiments, we examined the source of the discrepancy between the two studies. We revisited the effects of phonological similarity, word length, articulatory suppression, and irrelevant speech, using open and closed pools of words in backward and forward recall. The results are unequivocal in showing that none of these effects are influenced by recall direction, suggesting that Bireta et al.'s (Memory & Cognition 38:279-291, 2010) results are the consequence of their particular stimuli.}, } @article {pmid22078865, year = {2012}, author = {Gagnon, LL and Roberge, GD}, title = {Dissecting the journey: nursing student experiences with collaboration during the group work process.}, journal = {Nurse education today}, volume = {32}, number = {8}, pages = {945-950}, doi = {10.1016/j.nedt.2011.10.019}, pmid = {22078865}, issn = {1532-2793}, mesh = {Adolescent ; Adult ; *Attitude of Health Personnel ; Canada ; *Cooperative Behavior ; Education, Nursing, Baccalaureate/*organization & administration ; Female ; *Group Processes ; Humans ; Male ; Nursing Education Research ; Nursing Evaluation Research ; Nursing Methodology Research ; Qualitative Research ; Retrospective Studies ; Students, Nursing/*psychology ; Young Adult ; }, abstract = {Since the outset of nursing care, group work processes have evolved into essential components of a nurse's role and responsibilities within the health care system. To reflect this trend, group work is often utilized as a medium to promote professional socialization in undergraduate nursing curricula. The purpose of this qualitative study was to explore the ways undergraduate nursing students experience collaboration during group work activities. Braun and Clarke's (2006) theoretical thematic analysis combined with Pollio et al.'s (2006) interpretive framework was utilized to capture the students' lived experiences regarding group work. The participants of this study consisted of 96 undergraduate students enrolled in a nursing program in Canada. Written descriptions of their perceptions of their group work practices were analyzed to determine the extent to which these adhere to the collaborative practice essential elements (Jones and Way, 2006). Analysis of the results revealed an unexpected element of collaboration that of the psychosocial element in group work. The results from this study expose advantages and disadvantages of group work processes during group work in nursing education. This type of insight is valuable for educators to prepare nursing students for the complex demands of working with interdisciplinary teams.}, } @article {pmid22040045, year = {2011}, author = {Jauchem, JR}, title = {Author's response: My response to Dr. Dawes et al.'s letter follows (owing to the U.S. Air Force Research Laboratory's approval process required of authors, the response could not be submitted to the Journal of Forensic Sciences in a timely manner.}, journal = {Journal of forensic sciences}, volume = {56}, number = {6}, pages = {1671-1672}, doi = {10.1111/j.1556-4029.2011.01922.x}, pmid = {22040045}, issn = {1556-4029}, mesh = {Animals ; *Conducted Energy Weapon Injuries ; Electric Stimulation/*instrumentation ; *Hematocrit ; }, } @article {pmid22026491, year = {2011}, author = {Harding, E and Pettinari, CJ and Brown, D and Hayward, M and Taylor, C}, title = {Service user involvement in clinical guideline development and implementation: learning from mental health service users in the UK.}, journal = {International review of psychiatry (Abingdon, England)}, volume = {23}, number = {4}, pages = {352-357}, doi = {10.3109/09540261.2011.606802}, pmid = {22026491}, issn = {1369-1627}, mesh = {Humans ; Mental Disorders/psychology/*therapy ; Mental Health Services/*standards ; Patient Participation/*methods/psychology ; Practice Guidelines as Topic/*standards ; United Kingdom ; }, abstract = {The participation of service users and the public in the development of clinical guidelines is increasingly valued in international guideline programmes. This paper extends the findings of Harding et al.'s (2010) exploration of the views of service users who participated in developing NICE mental health guidelines. This analysis considered the relative value of personal versus professional knowledge and experience, the barriers to service users contributing effectively in guideline development, the unspoken 'rules' concerning decision making, and issues of power and group dynamics. We combine these insights with observations from research in guideline development and with advances in the recovery movement and in the shared decision-making clinical model to suggest areas of improvement in guideline development, notably: translating evidence to recommendations, optimizing the acceptability of treatment recommendations to service users, and reconciling different types of knowledge.}, } @article {pmid21993804, year = {2013}, author = {Wilson, F and Gott, M and Ingleton, C}, title = {Perceived risks around choice and decision making at end-of-life: a literature review.}, journal = {Palliative medicine}, volume = {27}, number = {1}, pages = {38-53}, doi = {10.1177/0269216311424632}, pmid = {21993804}, issn = {1477-030X}, mesh = {Choice Behavior ; *Decision Making ; Health Services Needs and Demand ; Humans ; Palliative Care/*methods ; Risk Factors ; Terminal Care/*psychology ; United Kingdom ; }, abstract = {BACKGROUND: the World Health Organization identifies meeting patient choice for care as central to effective palliative care delivery. Little is known about how choice, which implies an objective balancing of options and risks, is understood and enacted through decision making at end-of-life.

AIM: to explore how perceptions of 'risk' may inform decision-making processes at end-of-life.

DESIGN: an integrative literature review was conducted between January and February 2010. Papers were reviewed using Hawker et al.'s criteria and evaluated according to clarity of methods, analysis and evidence of ethical consideration. All literature was retained as background data, but given the significant international heterogeneity the final analysis specifically focused on the UK context.

DATA SOURCE: the databases Medline, PsycINFO, Assia, British Nursing Index, High Wire Press and CINAHL were explored using the search terms decision*, risk, anxiety, hospice and palliative care, end-of-life care and publication date of 1998-2010.

RESULTS: thematic analysis of 25 papers suggests that decision making at end-of-life is multifactorial, involving a balancing of risks related to caregiver support; service provider resources; health inequalities and access; challenges to information giving; and perceptions of self-identity. Overall there is a dissonance in understandings of choice and decision making between service providers and service users.

CONCLUSION: the concept of risk acknowledges the factors that shape and constrain end-of-life choices. Recognition of perceived risks as a central factor in decision making would be of value in acknowledging and supporting meaningful decision making processes for patients with palliative care needs and their families.}, } @article {pmid21984865, year = {2011}, author = {Berkman, ET and Lieberman, MD}, title = {What's outside the black box?: The status of behavioral outcomes in neuroscience research.}, journal = {Psychological inquiry}, volume = {22}, number = {2}, pages = {100-107}, pmid = {21984865}, issn = {1047-840X}, support = {F31 DA024904/DA/NIDA NIH HHS/United States ; }, abstract = {Kievit et al.'s target paper exemplifies a trend in recent years in psychology and neuroscience to focus on internal mental and neural processes without integrating actual behavior. We discuss the theoretical status of behavior in the context of their model, and present an extension of the model that explicitly includes behavior. Several theoretical and methodological issues relevant to integrating behavior into the model are considered, particularly the distinction between behavior as measured in the laboratory along with neural and psychological processes (proximal behavior) and behavior as measured in situ as part of ongoing daily experience (distal behavior). We conclude by describing several studies that integrate neural, psychological, and behavioral indicators and discuss how these kinds of studies can facilitate a better understanding of behavior and contribute to theory development.}, } @article {pmid21953139, year = {2012}, author = {Sharma, P and Welch, K and Hussain, H and Pelletier, SJ and Fontana, RJ and Marrero, J and Merion, RM}, title = {Incidence and risk factors of hepatocellular carcinoma recurrence after liver transplantation in the MELD era.}, journal = {Digestive diseases and sciences}, volume = {57}, number = {3}, pages = {806-812}, pmid = {21953139}, issn = {1573-2568}, support = {K08 DK088946/DK/NIDDK NIH HHS/United States ; UL1 RR024986/RR/NCRR NIH HHS/United States ; UL1RR024986/RR/NCRR NIH HHS/United States ; KO8 DK-088946/DK/NIDDK NIH HHS/United States ; }, mesh = {Aged ; Cadaver ; Carcinoma, Hepatocellular/*mortality/*surgery ; Female ; Graft Rejection/drug therapy/mortality ; Humans ; Immunosuppressive Agents/therapeutic use ; Incidence ; Kaplan-Meier Estimate ; Liver Neoplasms/*mortality/*surgery ; Liver Transplantation/mortality/*statistics & numerical data ; Male ; Middle Aged ; Neoplasm Recurrence, Local/*mortality ; Predictive Value of Tests ; Proportional Hazards Models ; Risk Factors ; Tissue Donors/statistics & numerical data ; Young Adult ; }, abstract = {BACKGROUND AND AIMS: Deceased donor liver transplantation (DDLT) rates for candidates with hepatocellular carcinoma (HCC) have significantly increased in the MELD era because of the extra priority given to these candidates. We examined the incidence and pre-DDLT radiological and donor factors associated with post-DDLT HCC recurrence in the MELD era.

METHODS: Outcomes of HCC candidates aged ≥18 years that underwent DDLT between 2/28/02 and 6/30/08 (n = 94) were reviewed. The primary outcome was biopsy-proven post-LT HCC recurrence at any site. Kaplan-Meier analysis was used to calculate the cumulative incidence and Cox regression was used to identify the predictors of post-LT HCC recurrence.

RESULTS: The median age of the 94 candidates who met the study criteria was 54 years, 64% had hepatitis C, median lab MELD was 13, and median pre-LT AFP was 47 ng/dl. Based upon pre-DDLT imaging, 94% candidates met the Milan criteria. The median waiting time to transplant was 47 days and 27% received pre-DDLT loco-regional therapy. Seventeen (18%) developed HCC recurrence after 2.1 median years with a cumulative incidence of 6.8, 12, and 19% at 1, 2, and 3 years post-DDLT. The pre-DDLT number of lesions (p = 0.015), largest lesion diameter (p = 0.008), and higher donor age (p = 0.002) were the significant predictors of HCC recurrence after adjusting for pre-LT loco-regional therapy and waiting time. Post-LT HCC recurrence (p < 0.0001) and higher donor age (p = 0.029) were associated with lower post-LT survival.

CONCLUSIONS: Post-LT HCC recurrence is higher in our MELD era cohort than the reported rate of 8% at 4 years in Mazzaferro et al.'s study. The risk of HCC recurrence was significantly associated with the number of lesions and size of the largest lesion at the time of DDLT as well as with older donor age. Risk stratification using a predictive model for post-LT HCC recurrence based on pre-LT imaging and donor factors may help guide candidate selection and tailoring of HCC surveillance strategies after LT.}, } @article {pmid21947765, year = {2011}, author = {Shera, CA and Olson, ES and Guinan, JJ}, title = {On cochlear impedances and the miscomputation of power gain.}, journal = {Journal of the Association for Research in Otolaryngology : JARO}, volume = {12}, number = {6}, pages = {671-676}, pmid = {21947765}, issn = {1438-7573}, support = {R01 DC003130/DC/NIDCD NIH HHS/United States ; DC003130/DC/NIDCD NIH HHS/United States ; R01 DC003687/DC/NIDCD NIH HHS/United States ; DC00235/DC/NIDCD NIH HHS/United States ; R01 DC000235/DC/NIDCD NIH HHS/United States ; R29 DC003130/DC/NIDCD NIH HHS/United States ; }, mesh = {Acoustic Impedance Tests/*methods/*standards ; Animals ; Basilar Membrane/*physiology ; Biomechanical Phenomena/physiology ; Biophysics/methods/standards ; Endolymph/physiology ; Gerbillinae ; *Models, Biological ; Organ of Corti/*physiology ; Pressure ; Reproducibility of Results ; Stapes/physiology ; }, abstract = {In their article, "Measurement of cochlear power gain in the sensitive gerbil ear," Ren et al. (Nat Commun 2:216, 2011) claim to provide "the first direct experimental evidence of power amplification in the sensitive living cochlea." While we recognize the technical challenges of the experiments and appreciate the beauty of the data, the authors' analysis and interpretation of the measurements are invalid. We review the concept of impedance (i.e., the ratio of pressure to velocity) as it applies to cochlear mechanics and show that Ren et al. mistakenly equate the impedances near the basilar membrane and stapes with the impedance characteristic of an infinite, uniform tube of fluid. As a consequence of this error, Ren et al.'s measurements and analysis provide no evidence for power amplification in the cochlea. Compelling evidence for power amplification has, however, been previously provided by others.}, } @article {pmid21935737, year = {2011}, author = {Matsukura, M and Hollingworth, A}, title = {Does visual short-term memory have a high-capacity stage?.}, journal = {Psychonomic bulletin & review}, volume = {18}, number = {6}, pages = {1098-1104}, pmid = {21935737}, issn = {1531-5320}, support = {R01 EY017356/EY/NEI NIH HHS/United States ; R01EY017356/EY/NEI NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Attention ; Cues ; Humans ; *Memory, Short-Term ; Pattern Recognition, Visual ; Visual Perception ; Young Adult ; }, abstract = {Visual short-term memory (VSTM) has long been considered a durable, limited-capacity system for the brief retention of visual information. However, a recent work by Sligte et al. (Plos One 3:e1699, 2008) reported that, relatively early after the removal of a memory array, a cue allowed participants to access a fragile, high-capacity stage of VSTM that is distinct from iconic memory. In the present study, we examined whether this stage division is warranted by attempting to corroborate the existence of an early, high-capacity form of VSTM. The results of four experiments did not support Sligte et al.'s claim, since we did not obtain evidence for VSTM retention that exceeded traditional estimates of capacity. However, performance approaching that observed in Sligte et al. can be achieved through extensive practice, providing a clear explanation for their findings. Our evidence favors the standard view of VSTM as a limited-capacity system that maintains a few object representations in a relatively durable form.}, } @article {pmid21935345, year = {2011}, author = {Bower, HA and Bowen, NK and Powers, JD}, title = {Family-Faculty Trust As Measured with the ESSP.}, journal = {Children & schools}, volume = {33}, number = {3}, pages = {158-167}, pmid = {21935345}, issn = {1532-8759}, support = {R41 DA013865/DA/NIDA NIH HHS/United States ; R42 DA013865/DA/NIDA NIH HHS/United States ; R43 DA020217/DA/NIDA NIH HHS/United States ; R44 DA020217/DA/NIDA NIH HHS/United States ; }, abstract = {The degree to which parents and teachers perceive they are working together in the best educational interests of children is a critical aspect of school culture. In previous work by Hoy, Tarter, and Woolfolk Hoy (2006), the phenomenon was named Faculty Trust and was measured with data from teachers. The current study builds upon Hoy et al.'s work by recommending that measures of Faculty Trust capture the important reciprocal nature of trust and cooperation between schools and families that is theoretically part of the original construct. Data collected from parents and teachers with the Elementary School Success Profile (ESSP) were used to test a broadened construct called Family-Faculty Trust. Confirmatory factor analyses (CFA) with Mplus indicated that items and composites on the ESSP could be used to measure a multidimensional Family-Faculty Trust construct. Implications for how school social workers can improve this aspect of school culture when total or subscale scores are found to be low are discussed.}, } @article {pmid21928934, year = {2012}, author = {Hanley, JR and Hayes, A}, title = {The irrelevant sound effect under articulatory suppression: is it a suffix effect?.}, journal = {Journal of experimental psychology. Learning, memory, and cognition}, volume = {38}, number = {2}, pages = {482-487}, doi = {10.1037/a0025600}, pmid = {21928934}, issn = {1939-1285}, mesh = {Acoustic Stimulation ; Analysis of Variance ; Auditory Perception/*physiology ; Female ; Humans ; Male ; Mental Recall/*physiology ; *Phonetics ; Reaction Time/physiology ; *Repression, Psychology ; Students ; Universities ; Verbal Behavior/*physiology ; }, abstract = {An experiment is reported that investigates the relation between the suffix effect and the effect of irrelevant sound on the serial recall of short sequences of spoken material. The main issue was whether there is an effect of irrelevant sound under articulatory suppression in the presence of a spoken suffix. As in Hanley and Bakopoulou (2003), the irrelevant sound comprised speech that was presented during the retention interval. When a spoken suffix appeared at the end of the list, a significant effect of irrelevant sound remained when participants were able to rehearse list items. However, it disappeared under articulatory suppression. The effects of irrelevant sound remained significant under suppression when the suffix was an auditory tone but was confined to the final position of the serial position curve. These results parallel those reported by Jones, Macken, and Nicholls (2004) and Jones, Hughes, and Macken (2006) when they examined the effect of articulatory suppression on the phonological similarity effect. The results are consistent with Jones et al.'s (2006, 2004) view that an acoustic-perceptual representation of the terminal list items is the source of the effects of irrelevant sound and phonological similarity when they occur in the presence of articulatory suppression.}, } @article {pmid21928916, year = {2011}, author = {Bem, DJ and Utts, J and Johnson, WO}, title = {Must psychologists change the way they analyze their data?.}, journal = {Journal of personality and social psychology}, volume = {101}, number = {4}, pages = {716-719}, doi = {10.1037/a0024777}, pmid = {21928916}, issn = {1939-1315}, mesh = {*Data Interpretation, Statistical ; Humans ; Psychology/*methods ; }, abstract = {Wagenmakers, Wetzels, Borsboom, and van der Maas (2011) argued that psychologists should replace the familiar "frequentist" statistical analyses of their data with bayesian analyses. To illustrate their argument, they reanalyzed a set of psi experiments published recently in this journal by Bem (2011), maintaining that, contrary to his conclusion, his data do not yield evidence in favor of the psi hypothesis. We argue that they have incorrectly selected an unrealistic prior distribution for their analysis and that a bayesian analysis using a more reasonable distribution yields strong evidence in favor of the psi hypothesis. More generally, we argue that there are advantages to bayesian analyses that merit their increased use in the future. However, as Wagenmakers et al.'s analysis inadvertently revealed, they contain hidden traps that must be better understood before being more widely substituted for the familiar frequentist analyses currently employed by most research psychologists.}, } @article {pmid21927847, year = {2011}, author = {Masi, S}, title = {Differences in gorilla nettle-feeding between captivity and the wild: local traditions, species typical behaviors or merely the result of nutritional deficiencies?.}, journal = {Animal cognition}, volume = {14}, number = {6}, pages = {921-925}, doi = {10.1007/s10071-011-0457-7}, pmid = {21927847}, issn = {1435-9456}, mesh = {Animals ; *Feeding Behavior ; Female ; *Gorilla gorilla ; *Learning ; Male ; *Motor Skills ; }, abstract = {Behavioral and cognitive studies on captive apes often pay little attention to the specific environmental conditions of their study subjects. A recent report form Byrne et al. (Anim Cogn doi: 10.1007/s10071-011-0403-8, 2011), comparing nettle-feeding techniques between captive and wild gorillas, claimed to document "the strongest evidence yet to come from any great ape that observational learning of a skilled conspecific" can allow social learning and culture in gorillas. An earlier study with similar findings placed emphasis instead on the many similarities and claims for species typical behavior, thus a genetic hypothesis instead of a cultural hypothesis. This commentary aims at formulating a third environmental hypothesis based on path-dependent behavioral differences owing to different diet and availability of nutritional resources of wild and captive gorillas. Captive diet provides gorillas with a much lower concentration of fibers. Gorillas are hindgut fermenters, and this deficit of natural fermentation of fibers may impact their health and their behavior in zoos. Results of Byrne et al.'s study will be discussed comparing feeding choice and availability of nutritional resources of wild and captive gorillas, showing that in captivity gorilla, motivation to consume certain food or certain plant parts may differ drastically from that of wild gorillas. This view does not intend to deny that social learning and culture may exist in gorillas, but to guide and encourage future works investigating social learning in great apes to take more accurately into account the living conditions and, when comparing populations, the possible environmental differences.}, } @article {pmid21927522, year = {2012}, author = {Kong, YY and Mullangi, A}, title = {On the development of a frequency-lowering system that enhances place-of-articulation perception.}, journal = {Speech communication}, volume = {54}, number = {1}, pages = {147-160}, pmid = {21927522}, issn = {0167-6393}, support = {R03 DC009684/DC/NIDCD NIH HHS/United States ; }, abstract = {Frequency lowering is a form of signal processing designed to deliver high-frequency speech cues to the residual hearing region of a listener with a high-frequency hearing loss. While this processing technique has been shown to improve the intelligibility of fricative and affricate consonants, perception of place of articulation has remained a challenge for hearing-impaired listeners, especially when the bandwidth of the speech signal is reduced during the frequency-lowering processing. This paper describes a modified vocoder-based frequency-lowering system similar to one reported by Posen, Reed, and Braida (1993), with the goal of improving place-of-articulation perception by enhancing the spectral differences of fricative consonants. In this system, frequency lowering is conditional; it suppresses the processing whenever the high-frequency portion (>400 Hz) of the speech signal is a periodic signal. In addition, the system separates non-sonorant consonants into three classes based on the spectral information (slope and peak location) of fricative consonants. Results from a group of normal-hearing listeners with our modified system show improved perception of frication and affrication features, as well as place-of-articulation distinction, without degrading the perception of nasals and semivowels compared to low-pass filtering and Posen et al.'s system.}, } @article {pmid21924426, year = {2011}, author = {Van Campen, A and De Groote, F and Bosmans, L and Scheys, L and Jonkers, I and De Schutter, J}, title = {Functional knee axis based on isokinetic dynamometry data: Comparison of two methods, MRI validation, and effect on knee joint kinematics.}, journal = {Journal of biomechanics}, volume = {44}, number = {15}, pages = {2595-2600}, doi = {10.1016/j.jbiomech.2011.08.022}, pmid = {21924426}, issn = {1873-2380}, mesh = {Adult ; *Algorithms ; Biomechanical Phenomena ; Female ; Humans ; Knee Joint/*physiology ; Male ; *Models, Biological ; Movement/*physiology ; Muscle Strength Dynamometer ; Range of Motion, Articular/*physiology ; }, abstract = {This paper compares geometry-based knee axes of rotation (transepicondylar axis and geometric center axis) and motion-based functional knee axes of rotation (fAoR). Two algorithms are evaluated to calculate fAoRs: Gamage and Lasenby's sphere fitting algorithm (GL) and Ehrig et al.'s axis transformation algorithm (SARA). Calculations are based on 3D motion data acquired during isokinetic dynamometry. AoRs are validated with the equivalent axis based on static MR-images. We quantified the difference in orientation between two knee axes of rotation as the angle between the projection of the axes in the transversal and frontal planes, and the difference in location as the distance between the intersection points of the axes with the sagittal plane. Maximum differences between fAoRs resulting from GL and SARA were 5.7° and 15.4mm, respectively. Maximum differences between fAoRs resulting from GL or SARA and the equivalent axis were 5.4°/11.5mm and 8.6°/12.8mm, respectively. Differences between geometry-based axes and EA are larger than differences between fAoR and EA both in orientation (maximum 10.6°).and location (maximum 20.8mm). Knee joint angle trajectories and the corresponding accelerations for the different knee axes of rotation were estimated using Kalman smoothing. For the joint angles, the maximum RMS difference with the MRI-based equivalent axis, which was used as a reference, was 3°. For the knee joint accelerations, the maximum RMS difference with the equivalent axis was 20°/s(2). Functional knee axes of rotation describe knee motion better than geometry-based axes. GL performs better than SARA for calculations based on experimental dynamometry.}, } @article {pmid21921298, year = {2011}, author = {Phillips, AJ and Czeisler, CA and Klerman, EB}, title = {Revisiting spontaneous internal desynchrony using a quantitative model of sleep physiology.}, journal = {Journal of biological rhythms}, volume = {26}, number = {5}, pages = {441-453}, pmid = {21921298}, issn = {1552-4531}, support = {P01-AG009975/AG/NIA NIH HHS/United States ; RC2-HL101340/HL/NHLBI NIH HHS/United States ; K24 HL105664/HL/NHLBI NIH HHS/United States ; RC2 HL101340/HL/NHLBI NIH HHS/United States ; M01 RR002635/RR/NCRR NIH HHS/United States ; P01 AG009975/AG/NIA NIH HHS/United States ; K24-HL105664/HL/NHLBI NIH HHS/United States ; }, mesh = {Biological Clocks/physiology ; Body Temperature/physiology ; Circadian Rhythm/*physiology ; Humans ; Hypothalamus/physiology ; *Models, Biological ; Sleep/*physiology ; Wakefulness/*physiology ; }, abstract = {Early attempts to characterize free-running human circadian rhythms generated three notable results: 1) observed circadian periods of 25 hours (considerably longer than the now established 24.1- to 24.2-hour average intrinsic circadian period) with sleep delayed to later circadian phases than during entrainment; 2) spontaneous internal desynchrony of circadian rhythms and sleep/wake cycles--the former with an approximately 24.9-hour period, and the latter with a longer (28-68 hour) or shorter (12-20 hour) period; and 3) bicircadian (48-50 hour) sleep/wake cycles. All three results are reproduced by Kronauer et al.'s (1982) coupled oscillator model, but the physiological basis for that phenomenological model is unclear. We use a physiologically based model of hypothalamic and brain stem nuclei to investigate alternative physiological mechanisms that could underlie internal desynchrony. We demonstrate that experimental observations can be reproduced by changes in two pathways: promotion of orexinergic (Orx) wake signals, and attenuation of the circadian signal reaching hypothalamic nuclei. We reason that delayed sleep is indicative of an additional wake-promoting drive, which may be of behavioral origin, associated with removal of daily schedules and instructions given to participants. We model this by increasing Orx tone during wake, which reproduces the observed period lengthening and delayed sleep. Weakening circadian input to the ventrolateral preoptic nucleus (possibly mediated by the dorsomedial hypothalamus) causes desynchrony, with observed sleep/wake cycle period determined by degree of Orx up-regulation. During desynchrony, sleep/wake cycles are driven by sleep homeostasis, yet sleep bout length maintains circadian phase dependence. The model predicts sleep episodes are shortest when started near the temperature minimum, consistent with experimental findings. The model also correctly predicts that it is possible to transition to bicircadian rhythms from either a synchronized or desynchronized state. Our findings suggest that feedback from behavioral choices to physiology could play an important role in spontaneous internal desynchrony.}, } @article {pmid21913586, year = {2011}, author = {Gagnon, D}, title = {Global Health Research Initiative (GHRI): a response to Larson et al.'s commentary on Grand Challenges Canada in CJPH 2011;102(2):149-51.}, journal = {Canadian journal of public health = Revue canadienne de sante publique}, volume = {102}, number = {4}, pages = {293}, pmid = {21913586}, issn = {0008-4263}, mesh = {Biomedical Research/*standards ; *Global Health ; Health Services Research/*standards ; Humans ; }, } @article {pmid21910538, year = {2012}, author = {Franklin, A and Gibbons, E and Chittenden, K and Alvarez, J and Taylor, C}, title = {Infant color preference for red is not selectively context specific.}, journal = {Emotion (Washington, D.C.)}, volume = {12}, number = {5}, pages = {1155-1160}, doi = {10.1037/a0025333}, pmid = {21910538}, issn = {1931-1516}, mesh = {Anger ; *Choice Behavior ; Color ; *Color Perception ; *Emotions ; Facial Expression ; Happiness ; Humans ; Infant ; Photic Stimulation ; }, abstract = {It has been proposed that human infants, like nonhuman primates, respond favorably to red in hospitable contexts, yet unfavorably in hostile contexts (Maier, Barchfeld, Elliot, & Pekrun, 2009). Here, we replicate and extend the study (Maier et al., 2009) whose findings have been used to support this hypothesis. As in Maier et al., 1-year-old infants were shown a photograph of a happy or angry face before pairs of colors were presented, yet in the current study, the set of stimuli crucially included two colors that are typically preferred by infants (red and blue). The percentage of times that infants looked first at the colors was analyzed for the two emotional "contexts." Following the happy face, infants looked first at red and blue equally, but significantly more than green. Following the angry face, the pattern of looking preference was the same as following the happy face, but the variation across the three colors was reduced. Contrary to Maier et al.'s hypothesis, there was no evidence that infants are selectively averse to red in angry contexts: following the angry face, "preference" for both red and blue was reduced, but was not significantly below chance. We therefore suggest an alternative account to Maier et al.'s evolutionary hypothesis, which argues that an angry face merely removes infant color preference, potentially due to the perceptual characteristics of the angry face disrupting infants' encoding of color.}, } @article {pmid21908439, year = {2011}, author = {Kuijpers, KF and van der Knaap, LM and Lodewijks, IA}, title = {Victims' influence on intimate partner violence revictimization: a systematic review of prospective evidence.}, journal = {Trauma, violence & abuse}, volume = {12}, number = {4}, pages = {198-219}, doi = {10.1177/1524838011416378}, pmid = {21908439}, issn = {1552-8324}, mesh = {Battered Women/*psychology ; Crime Victims/*psychology ; Female ; Humans ; *Internal-External Control ; *Interpersonal Relations ; Male ; Models, Psychological ; Risk Assessment/methods ; Risk Factors ; Secondary Prevention ; Self Concept ; Social Adjustment ; Spouse Abuse/*psychology/statistics & numerical data ; }, abstract = {Foa, Cascardi, Zoellner and Feeny developed two models of women's influence on intimate partner violence (IPV), which integrate victim-related variables associated with the cessation or continuation of partner violence (i.e., repeat IPV). One of the models focuses on psychological factors while the other centers on environmental factors. Central to both models are three key factors: partner violence; psychological difficulties; and resilience. Despite the appeal of these models, empirical, prospective research that specifically tests these models appears to be lacking. This article describes a systematic review of the available literature that examines the prospective link between the three key factors of the models and the risk of IPV revictimization. A synthesis of 15 studies reveals that Foa et al.'s models of revictimization are partly supported by prior prospective research. It is beyond doubt that the key factor partner violence (involving the severity and frequency of prior IPV) is a strong predictor for IPV revictimization; the evidence regarding victims' psychological difficulties and resilience is more mixed. Findings are discussed in terms of implications for practice and research and might enable practitioners to help victims to take control of their situations and to contribute to their empowerment. The importance of future prospective research into dynamic, victim-related variables is emphasized, in order to further support Foa's models of victims' influence on IPV revictimization.}, } @article {pmid21905566, year = {2011}, author = {Howells, K and Jones, L and Harris, M and Wong, S and Daffern, M and Tombs, D and Kane, E and Gallagher, J and Ijomah, G and Krishnan, G and Milton, J and Thornton, D}, title = {The baby, the bathwater and the bath itself: a response to Tyrer et al.'s review of the successes and failures of dangerous and severe personality disorder.}, journal = {Medicine, science, and the law}, volume = {51}, number = {3}, pages = {129-133}, doi = {10.1258/msl.2010.010083}, pmid = {21905566}, issn = {0025-8024}, mesh = {*Dangerous Behavior ; Forensic Psychiatry/*organization & administration ; Humans ; Mental Health Services/*organization & administration ; Personality Disorders/*therapy ; }, abstract = {A recent paper by Tyrer et al. in this journal has reviewed the dangerous and severe personality disorder (DSPD) initiative in the assessment and management of severe personality disorder associated with high risk. This previous paper summarized the authors' perceptions of the successes and failures of the DSPD pilot. In the present paper we identify some inaccuracies in the previous review and provide a critique of the conclusions reached.}, } @article {pmid21899426, year = {2011}, author = {Matroud, AA and Tuffley, CP and Hendy, MD}, title = {An algorithm to solve the motif alignment problem for approximate nested tandem repeats in biological sequences.}, journal = {Journal of computational biology : a journal of computational molecular cell biology}, volume = {18}, number = {9}, pages = {1211-1218}, doi = {10.1089/cmb.2011.0101}, pmid = {21899426}, issn = {1557-8666}, mesh = {*Algorithms ; Data Mining/methods ; Sequence Alignment/*methods ; Sequence Analysis, DNA/*methods ; *Tandem Repeat Sequences ; }, abstract = {An approximate nested tandem repeat (NTR) in a string T is a complex repetitive structure consisting of many approximate copies of two substrings x and X ("motifs") interspersed with one another. NTRs fall into a class of repetitive structures broadly known as subrepeats. NTRs have been found in real DNA sequences and are expected to be important in evolutionary biology, both in understanding evolution of the ribosomal DNA (where NTRs can occur), and as a potential marker in population genetic and phylogenetic studies. This article describes an alignment algorithm for the verification phase of the software tool NTRFinder developed for database searches for NTRs. When the search algorithm has located a subsequence containing a possible NTR, with motifs X and x, a verification step aligns this subsequence against an exact NTR built from the templates X and x, to determine whether the subsequence contains an approximate NTR and its extent. This article describes an algorithm to solve this alignment problem in O(|T|(|X| + |x|)) space and time. The algorithm is based on Fischetti et al.'s wrap-around dynamic programming.}, } @article {pmid21895824, year = {2011}, author = {Fischer, B and Kendall, P}, title = {Nutt et al.'s harm scales for drugs--room for improvement but better policy based on science with limitations than no science at all.}, journal = {Addiction (Abingdon, England)}, volume = {106}, number = {11}, pages = {1891-2; discussion 1896-8}, doi = {10.1111/j.1360-0443.2011.03487.x}, pmid = {21895824}, issn = {1360-0443}, mesh = {*Crime ; Drug and Narcotic Control/*legislation & jurisprudence ; Humans ; Illicit Drugs/*legislation & jurisprudence ; *Violence ; }, } @article {pmid21895397, year = {2011}, author = {Staub, A and Grant, M and Clifton, C and Rayner, K}, title = {Still no phonological typicality effect on word reading time (and no good explanation of one, either): a rejoinder to Farmer, Monaghan, Misyak, and Christiansen.}, journal = {Journal of experimental psychology. Learning, memory, and cognition}, volume = {37}, number = {5}, pages = {1326-1328}, pmid = {21895397}, issn = {1939-1285}, support = {R01 HD065829/HD/NICHD NIH HHS/United States ; HD26765/HD/NICHD NIH HHS/United States ; HD065829/HD/NICHD NIH HHS/United States ; R37 HD026765/HD/NICHD NIH HHS/United States ; HD18708/HD/NICHD NIH HHS/United States ; R01 HD026765/HD/NICHD NIH HHS/United States ; R01 HD018708/HD/NICHD NIH HHS/United States ; }, mesh = {*Eye Movements ; *Fixation, Ocular ; Humans ; *Phonetics ; *Reaction Time ; *Reading ; *Semantics ; }, abstract = {In this brief rejoinder, we respond to Farmer, Monaghan, Misyak, and Christiansen (2011). We argue that the data still do not support the claim that reading time is affected by the phonological typicality of a word for its part of speech. We also question Farmer et al.'s claim that interleaving syntactic structures in an experiment modifies grammatically based syntactic expectations.}, } @article {pmid21895396, year = {2011}, author = {Farmer, TA and Monaghan, P and Misyak, JB and Christiansen, MH}, title = {Phonological typicality influences sentence processing in predictive contexts: reply to Staub, Grant, Clifton, and Rayner (2009).}, journal = {Journal of experimental psychology. Learning, memory, and cognition}, volume = {37}, number = {5}, pages = {1318-1325}, doi = {10.1037/a0023063}, pmid = {21895396}, issn = {1939-1285}, mesh = {*Eye Movements ; *Fixation, Ocular ; Humans ; *Phonetics ; *Reaction Time ; *Reading ; *Semantics ; }, abstract = {In 2 separate self-paced reading experiments, Farmer, Christiansen, and Monaghan (2006) found that the degree to which a word's phonology is typical of other words in its lexical category influences online processing of nouns and verbs in predictive contexts. Staub, Grant, Clifton, and Rayner (2009) failed to find an effect of phonological typicality when they combined stimuli from the separate experiments into a single experiment. We replicated Staub et al.'s experiment and found that the combination of stimulus sets affects the predictiveness of the syntactic context; this reduces the phonological typicality effect as the experiment proceeds, although the phonological typicality effect was still evident early in the experiment. Although an ambiguous context may diminish sensitivity to the probabilistic relationship between the sound of a word and its lexical category, phonological typicality does influence online sentence processing during normal reading when the syntactic context is predictive of the lexical category of upcoming words.}, } @article {pmid21886482, year = {2011}, author = {May, RM}, title = {Why worry about how many species and their loss?.}, journal = {PLoS biology}, volume = {9}, number = {8}, pages = {e1001130}, pmid = {21886482}, issn = {1545-7885}, mesh = {*Biota ; *Earth, Planet ; }, abstract = {We are astonishingly ignorant about how many species are alive on earth today, and even more ignorant about how many we can lose yet still maintain ecosystem services that humanity ultimately depends upon. Mora et al.'s paper is important in offering an imaginative new approach to assessing total species numbers, both on land and in the sea.}, } @article {pmid21880284, year = {2011}, author = {Tee, J and Dissanayake, C}, title = {Can 15-month-old infants understand pretence? An investigation using the 'violation-of-expectation' paradigm.}, journal = {Acta psychologica}, volume = {138}, number = {2}, pages = {316-321}, doi = {10.1016/j.actpsy.2011.07.006}, pmid = {21880284}, issn = {1873-6297}, mesh = {*Child Development ; Cognition ; *Comprehension ; *Concept Formation ; Female ; Humans ; Infant ; *Interpersonal Relations ; Male ; Visual Perception ; }, abstract = {Productive tests are unsuitable for measuring infants' earliest understanding of pretence, because performance demands may render infants unable to produce the actions required to pass the test. Recently, Onishi, Baillargeon and Leslie (2007) used the violation-of-expectation (VOE) paradigm as a measure of infants' understanding of others' pretence that is free from such performance demands. They found that 15-month-old infants looked longer at an Unexpected event in which an actor pretended to pour into one cup but pretended to drink from another cup, compared to pretending to pour and drink with the same cup. On this basis, they argued that 15-month-old infants expect others' pretence to be consistent, demonstrating their understanding of others' pretence. However, infants may have responded to expectations they had about familiar action sequences, rather than to pretence per se. To test this hypothesis, the current study firstly replicated Onishi et al.'s results in a sample of 28 typically developing 15-month-old infants, and then added a condition using closely matched real versions of their pretend VOE tasks. It was found that infants looked longer at unexpected events, whether or not the events were real or pretend. It was concluded that 15-month-old infants may look longer at pretend events due to violations of expectations they have about familiar action sequences, rather than because they understand others' pretence behaviour.}, } @article {pmid21875168, year = {2012}, author = {Mattson, RE and O'Farrell, TJ and Lofgreen, AM and Cunningham, K and Murphy, CM}, title = {The role of illicit substance use in a conceptual model of intimate partner violence in men undergoing treatment for alcoholism.}, journal = {Psychology of addictive behaviors : journal of the Society of Psychologists in Addictive Behaviors}, volume = {26}, number = {2}, pages = {255-264}, pmid = {21875168}, issn = {1939-1501}, support = {R01 AA010796/AA/NIAAA NIH HHS/United States ; }, mesh = {Adult ; Aggression/*psychology ; Alcoholic Intoxication/epidemiology ; Alcoholism/*epidemiology/psychology/rehabilitation ; Antisocial Personality Disorder/epidemiology ; Dose-Response Relationship, Drug ; Female ; Humans ; *Interpersonal Relations ; Male ; *Models, Theoretical ; Psychiatric Status Rating Scales ; Risk Factors ; Sex Distribution ; Spouse Abuse/psychology/rehabilitation/*statistics & numerical data ; Substance Abuse Treatment Centers ; Substance-Related Disorders/*epidemiology/psychology/rehabilitation ; }, abstract = {Illicit substance use (ISU) predicts intimate partner violence (IPV) above and beyond alcohol use and other known IPV correlates. Stuart and colleagues (2008) provided evidence for a theoretical framework by which ISU contributes both directly and indirectly to IPV. We sought to replicate and extend their findings using data from 181 married or cohabiting heterosexual couples in which the male had recently begun a substance abuse treatment program and met criteria for alcohol dependence (97%) or abuse (3%). Using SEM, we found that (a) Stuart et al.'s model provided a good fit to the data; (b) men's cocaine use and women's sedative use emerged as particularly relevant to their respective perpetration of IPV; (c) a positive association between men's antisociality and physical aggression was mediated by increased stimulant use; and (d) the specific pattern of IPV predicted by women's sedative use differed across levels of aggression severity. These findings not only highlight the direct role of ISU in relationship aggression, but also support a larger theory-driven model comprising various proximal and distal precursors of IPV.}, } @article {pmid21872157, year = {2011}, author = {Barbet, S and Robert, G and Deminière, C and Maurice-Tison, S and Ferrière, JM}, title = {[Comparative study of periprostatic tissues thickness after retropubic or laparoscopic radical prostatectomy].}, journal = {Progres en urologie : journal de l'Association francaise d'urologie et de la Societe francaise d'urologie}, volume = {21}, number = {8}, pages = {542-548}, doi = {10.1016/j.purol.2010.10.004}, pmid = {21872157}, issn = {1166-7087}, mesh = {Aged ; Humans ; *Laparoscopy ; Male ; Middle Aged ; Prospective Studies ; Prostate/*pathology ; *Prostatectomy/methods ; Prostatic Neoplasms/*pathology/*surgery ; }, abstract = {OBJECTIVE: Analysing periprostatic tissue (PPT) thickness after retropubic (RP) or laparoscopic (LP) prostatectomy.

MATERIAL: From January to December 2007, 114 consecutives prostatectomies were performed in our institution (38 RP, 76 LP). Clinical data were prospectively collected in a database. Gardner et al.'s (1988) procedure was used for pathological analysis. PPT thickness was measured on pathological specimens by a single observer on a single microscope. The observer had no knowledge of either clinical data or surgical approach. Four levels were chosen (at the base, the proximal part, the distal part, the apex) and 12 standardized measures were performed on each level, 48 measures: a prostate. We compared PPT thickness and surgical margins according to surgical approach and clinical data.

RESULTS: Comparative analysis confirmed that LP and RP groups were similar as far as it concerns preoperative and pathological findings. Positive margin rate was also similar in LP and RP groups (4% versus 5.3%; P=0,37). Overall PPT thickness was thinner after LP than after RP except at the apex and the anterior face. Nevertheless, in the "complete preservation" group, PPT thickness was thinner at the apex in the RP group, thinner at the base in the LP group.

CONCLUSION: Measuring PPT thickness was an original objective and reproducible way to compare different techniques and new technologies for radical prostatectomy. PPT sparing was different but not better with the laparoscopic approach.}, } @article {pmid21864984, year = {2011}, author = {Arbeau, KJ and Kuiken, D and Wild, TC}, title = {Drinking to enhance and to cope: a daily process study of motive specificity.}, journal = {Addictive behaviors}, volume = {36}, number = {12}, pages = {1174-1183}, doi = {10.1016/j.addbeh.2011.07.020}, pmid = {21864984}, issn = {1873-6327}, mesh = {*Adaptation, Psychological ; Affect ; Alcohol Drinking/*psychology ; Canada ; Conscience ; Female ; Humans ; Internet ; Male ; Motivation ; Stress, Psychological ; Students/*psychology ; Surveys and Questionnaires ; Universities ; Young Adult ; }, abstract = {OBJECTIVE: Daily process studies of internal drinking motives have not examined motive specificity, i.e., whether theoretically plausible trait and situational antecedents differ in their ability to predict the extent to which alcohol consumption on any given day is motivated by coping or enhancement.

METHOD: University students (N=81) completed trait measures of coping and enhancement-motivated drinking (trait CM and EM), sensation seeking, and conscientiousness, and then completed a 14-day online diary assessing daily completion of tasks, daily alcohol use, and (on days when alcohol was consumed) the extent to which drinking was motivated by coping or enhancement (daily CM and EM).

RESULTS: Hierarchical linear models revealed unique situational and trait antecedents of daily CM and EM. In the daily EM drinking model, main effects of daily positive affect (b=0.11, p<0.05), trait EM (b=2.88, p<0.01), and trait sensation seeking (b=0.36, p<0.01) were qualified by cross-level interactions between daily task accomplishment and trait conscientiousness (b=0.03, p<0.01), and daily task accomplishment and trait sensation seeking (b=0.03, p<0.01). In the daily CM drinking model, main effects of daily positive affect (b=-0.08, p<0.05), daily negative affect (b=0.13, p<0.05), and trait CM (b=4.40, p<0.01), were qualified by cross-level interactions between trait CM and daily positive affect (b=-0.12, p<0.05), trait CM and daily negative affect (b=0.18, p<0.01), and trait conscientiousness and daily task accomplishment (b=0.01, p<0.01).

CONCLUSION: Our results replicated and extended Cooper et al.'s (1995) findings on the differential roles of sensation seeking and negative affect in CM and EM drinking at the daily level, and call into question the view that drinking motives should be solely conceptualized as individual difference variables. Theoretical and applied implications of the findings are discussed.}, } @article {pmid21861684, year = {2012}, author = {Foley, E and Rippon, G and Thai, NJ and Longe, O and Senior, C}, title = {Dynamic facial expressions evoke distinct activation in the face perception network: a connectivity analysis study.}, journal = {Journal of cognitive neuroscience}, volume = {24}, number = {2}, pages = {507-520}, doi = {10.1162/jocn_a_00120}, pmid = {21861684}, issn = {1530-8898}, mesh = {Adult ; Brain/*physiology ; Brain Mapping ; Emotions/*physiology ; Face ; *Facial Expression ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Nerve Net/*physiology ; Neurons/physiology ; Photic Stimulation ; Visual Perception/*physiology ; }, abstract = {Very little is known about the neural structures involved in the perception of realistic dynamic facial expressions. In the present study, a unique set of naturalistic dynamic facial emotional expressions was created. Through fMRI and connectivity analysis, a dynamic face perception network was identified, which is demonstrated to extend Haxby et al.'s [Haxby, J. V., Hoffman, E. A., & Gobbini, M. I. The distributed human neural system for face perception. Trends in Cognitive Science, 4, 223-233, 2000] distributed neural system for face perception. This network includes early visual regions, such as the inferior occipital gyrus, which is identified as insensitive to motion or affect but sensitive to the visual stimulus, the STS, identified as specifically sensitive to motion, and the amygdala, recruited to process affect. Measures of effective connectivity between these regions revealed that dynamic facial stimuli were associated with specific increases in connectivity between early visual regions, such as the inferior occipital gyrus and the STS, along with coupling between the STS and the amygdala, as well as the inferior frontal gyrus. These findings support the presence of a distributed network of cortical regions that mediate the perception of different dynamic facial expressions.}, } @article {pmid21859228, year = {2011}, author = {Reis, HT and Maniaci, MR and Caprariello, PA and Eastwick, PW and Finkel, EJ}, title = {In live interaction, does familiarity promote attraction or contempt? Reply to Norton, Frost, and Ariely (2011).}, journal = {Journal of personality and social psychology}, volume = {101}, number = {3}, pages = {575-578}, doi = {10.1037/a0023471}, pmid = {21859228}, issn = {1939-1315}, mesh = {*Disclosure ; Female ; Humans ; *Interpersonal Relations ; Male ; *Social Desirability ; }, abstract = {In this reply, we address and refute each of Norton, Frost, and Ariely's (see record 2011-18560-001) specific objections to the conclusion that, ceteris paribus, familiarity breeds liking in live interaction. In particular, we reiterate the importance of studying live interaction rather than decontextualized processes. These rebuttals notwithstanding, we concur with Norton et al.'s call for an integrative model that encompasses both Norton, Frost, and Ariely's (see record 2006-23056-008) results and ours (see record 2011-04644-001), and we point readers toward a description of a possible model presented in our original article.}, } @article {pmid21854379, year = {2011}, author = {Flood, SJ and Mitchell, WJ and Oxnard, CE and Turlach, BA and McGeachie, J}, title = {To evaluate the utility of smaller sample sizes when assessing dental maturity curves for forensic age estimation.}, journal = {Journal of forensic sciences}, volume = {56}, number = {6}, pages = {1604-1609}, doi = {10.1111/j.1556-4029.2011.01884.x}, pmid = {21854379}, issn = {1556-4029}, mesh = {Adolescent ; Age Determination by Teeth/*methods ; Analysis of Variance ; Australia ; Child ; Child, Preschool ; Female ; Forensic Dentistry ; Humans ; Linear Models ; Male ; Radiography, Panoramic ; *Sample Size ; Tooth Calcification ; }, abstract = {Dental maturation and chronological age estimation were determined from 144 healthy Western Australian individuals aged 3.6-14.5 years. The results were compared with Farah et al.'s previous study which comprised a larger heterogeneous sample of Western Australian individuals (n = 1450). Orthopantomograms were analyzed with the application of Demirjian and Goldstein's 4-tooth method based on eight stages of dental mineralization. Analysis of variance revealed no significant differences in dental maturity scores in each age group among the males in both studies; similar results were seen in the females. Paired t-tests showed no statistical significance overall between chronological and estimated ages for the males in our sample (p = 0.181), whereas the females showed significant differences (p < 0.001). Our results show that smaller samples may be used when assessing dental maturity curves for forensic age estimation.}, } @article {pmid21818223, year = {2011}, author = {Scheffer, C}, title = {A Summary and Commentary on Smith et al.'s "Why peer discussion improves student performance on in-class concept questions" (Science 2009).}, journal = {GMS Zeitschrift fur medizinische Ausbildung}, volume = {28}, number = {1}, pages = {Doc08}, pmid = {21818223}, issn = {1860-3572}, } @article {pmid21798965, year = {2011}, author = {Iwata, NK and Kwan, JY and Danielian, LE and Butman, JA and Tovar-Moll, F and Bayat, E and Floeter, MK}, title = {White matter alterations differ in primary lateral sclerosis and amyotrophic lateral sclerosis.}, journal = {Brain : a journal of neurology}, volume = {134}, number = {Pt 9}, pages = {2642-2655}, pmid = {21798965}, issn = {1460-2156}, support = {//Intramural NIH HHS/United States ; }, mesh = {Amyotrophic Lateral Sclerosis/*pathology/physiopathology ; Anisotropy ; Corpus Callosum/*pathology ; Diffusion Tensor Imaging ; Female ; Humans ; Male ; Middle Aged ; Motor Neuron Disease/*pathology/physiopathology ; Nerve Fibers, Myelinated/*pathology ; Pyramidal Tracts/*pathology ; }, abstract = {Primary lateral sclerosis is a sporadic disorder characterized by slowly progressive corticospinal dysfunction. Primary lateral sclerosis differs from amyotrophic lateral sclerosis by its lack of lower motor neuron signs and long survival. Few pathological studies have been carried out on patients with primary lateral sclerosis, and the relationship between primary lateral sclerosis and amyotrophic lateral sclerosis remains uncertain. To detect in vivo structural differences between the two disorders, diffusion tensor imaging of white matter tracts was carried out in 19 patients with primary lateral sclerosis, 18 patients with amyotrophic lateral sclerosis and 19 age-matched controls. Fibre tracking was used to reconstruct the intracranial portion of the corticospinal tract and three regions of the corpus callosum: the genu, splenium and callosal fibres connecting the motor cortices. Both patient groups had reduced fractional anisotropy, a measure associated with axonal organization, and increased mean diffusivity of the reconstructed corticospinal and callosal motor fibres compared with controls, without changes in the genu or splenium. Voxelwise comparison of the whole brain white matter using tract-based spatial statistics confirmed the differences between patients and controls in the diffusion properties of the corticospinal tracts and motor fibres of the callosum. This analysis further revealed differences in the regional distribution of white matter alterations between the patient groups. In patients with amyotrophic lateral sclerosis, the greatest reduction in fractional anisotropy occurred in the distal portions of the intracranial corticospinal tract, consistent with a distal axonal degeneration. In patients with primary lateral sclerosis, the greatest loss of fractional anisotropy and mean diffusivity occurred in the subcortical white matter underlying the motor cortex, with reduced volume, suggesting tissue loss. Clinical measures of upper motor neuron dysfunction correlated with reductions in fractional anisotropy in the corticospinal tract in patients with amyotrophic lateral sclerosis and increased mean diffusivity and volume loss of the corticospinal tract in patients with primary lateral sclerosis. Changes in the diffusion properties of the motor fibres of the corpus callosum were strongly correlated with changes in corticospinal fibres in patients, but not in controls. These findings indicate that degeneration is not selective for corticospinal neurons, but affects callosal neurons within the motor cortex in motor neuron disorders.}, } @article {pmid21787104, year = {2011}, author = {Lu, A and Mo, L and Hodges, BH}, title = {The weight of time: affordances for an integrated magnitude system.}, journal = {Journal of experimental psychology. Human perception and performance}, volume = {37}, number = {6}, pages = {1855-1866}, doi = {10.1037/a0024673}, pmid = {21787104}, issn = {1939-1277}, mesh = {Female ; Humans ; Judgment ; Male ; Mathematics ; Time Factors ; *Time Perception/physiology ; *Weight-Bearing/physiology ; Young Adult ; }, abstract = {In five experiments we explored the effects of weight on time in different action contexts to test the hypothesis that an integrated magnitude system is tuned to affordances. Larger magnitudes generally seem longer; however, Lu and colleagues (2009) found that if numbers were presented as weights in a range heavy enough to affect lifting, the "larger seems longer" effect was enhanced, but it was eliminated with weights too light to affect lifting. Experiments 1 and 2 revealed that actually lifting kilogram and gram weights had effects parallel to symbolized weights, suggesting that Lu et al.'s task implicitly evoked a lifting context. Experiments 3 and 4 showed that weights too heavy (e.g., tons) or too light to be discriminated by lifting, but relevant to other affordances (e.g., grams of a toxin) had effects on time as large or larger than for kilograms. Experiment 5 showed that the effect for grams in a toxicology context did not generalize to the lifting task of Experiment 2. Weight appears to integrate with other magnitudes when it is relevant to meaningful actions, including but not limited to lifting.}, } @article {pmid21782532, year = {2011}, author = {Pang, XF}, title = {The theory of bio-energy transport in the protein molecules and its properties.}, journal = {Physics of life reviews}, volume = {8}, number = {3}, pages = {264-286}, doi = {10.1016/j.plrev.2011.06.001}, pmid = {21782532}, issn = {1873-1457}, mesh = {Biological Transport ; *Biophysical Phenomena ; *Energy Metabolism ; Models, Chemical ; Protein Structure, Secondary ; Proteins/*chemistry/metabolism ; }, abstract = {The bio-energy transport is a basic problem in life science and related to many biological processes. Therefore to establish the mechanism of bio-energy transport and its theory have an important significance. Based on different properties of structure of α-helical protein molecules some theories of bio-energy transport along the molecular chains have been proposed and established, where the energy is released by hydrolysis of adenosine triphosphate (ATP). A brief survey of past researches on different models and theories of bio-energy, including Davydov's, Takeno's, Yomosa's, Brown et al.'s, Schweitzer's, Cruzeiro-Hansson's, Forner's and Pang's models were first stated in this paper. Subsequently we studied and reviewed mainly and systematically the properties, thermal stability and lifetimes of the carriers (solitons) transporting the bio-energy at physiological temperature 300 K in Pang's and Davydov's theories. From these investigations we know that the carrier (soliton) of bio-energy transport in the α-helical protein molecules in Pang's model has a higher binding energy, higher thermal stability and larger lifetime at 300 K relative to those of Davydov's model, in which the lifetime of the new soliton at 300 K is enough large and belongs to the order of 10(-10) s or τ/τ(0)≥700. Thus we can conclude that the soliton in Pang's model is exactly the carrier of the bio-energy transport, Pang's theory is appropriate to α-helical protein molecules.}, } @article {pmid21777321, year = {2012}, author = {Morgan, CJ and Curran, HV and , }, title = {Ketamine use: a review.}, journal = {Addiction (Abingdon, England)}, volume = {107}, number = {1}, pages = {27-38}, doi = {10.1111/j.1360-0443.2011.03576.x}, pmid = {21777321}, issn = {1360-0443}, mesh = {Abdominal Pain/chemically induced ; Acute Disease ; Anesthetics, Dissociative/adverse effects/pharmacology/*therapeutic use ; Animals ; Behavior, Addictive/epidemiology/psychology ; Child ; Chronic Disease ; Cognitive Dysfunction/chemically induced ; Cystitis/*chemically induced ; Educational Status ; Humans ; Ketamine/adverse effects/pharmacology/*therapeutic use ; Male ; Memory Disorders/*chemically induced ; Rats ; Risk-Taking ; Substance-Related Disorders/complications/*epidemiology/psychology ; Young Adult ; }, abstract = {AIMS: Ketamine remains an important medicine in both specialist anaesthesia and aspects of pain management. At the same time, its use as a recreational drug has spread in many parts of the world during the past few years. There are now increasing concerns about the harmful physical and psychological consequences of repeated misuse of this drug. The aim of this review was to survey and integrate the research literature on physical, psychological and social harms of both acute and chronic ketamine use.

METHOD: The literature on ketamine was systematically searched and findings were classified into the matrix of Nutt et al.'s (2007) rational scale for assessing the harms of psychoactive substances.

RESULTS: A major physical harm is ketamine induced ulcerative cystitis which, although its aetiology is unclear, seems particularly associated with chronic, frequent use of the drug. Frequent, daily use is also associated with neurocognitive impairment and, most robustly, deficits in working and episodic memory. Recent studies suggest certain neurological abnormalities which may underpin these cognitive effects. Many frequent users are concerned about addiction and report trying but failing to stop using ketamine.

CONCLUSIONS: The implications of these findings are drawn out for treatment of ketamine-induced ulcerative cystitis in which interventions from urologists and from addiction specialists should be coordinated. Neurocognitive impairment in frequent users can impact negatively upon achievement in education and at work, and also compound addiction problems. Prevention and harm minimization campaigns are needed to alert young people to these harmful and potentially chronic effects of ketamine.}, } @article {pmid21773678, year = {2011}, author = {Virányi, Z and Range, F}, title = {Evaluating the logic of perspective-taking experiments.}, journal = {Learning & behavior}, volume = {39}, number = {4}, pages = {306-309}, pmid = {21773678}, issn = {1543-4508}, support = {P 21244/FWF_/Austrian Science Fund FWF/Austria ; }, mesh = {Animals ; *Behavior, Animal ; Female ; Humans ; Male ; *Theory of Mind ; Wolves/*psychology ; }, abstract = {In their recent study, Udell, Dorey, and Wynne (in press)[COMP: Ref. is LBE0034. Will have to be updated to (2011) here and in LBE0038, once page nos. are available.] showed that in a begging task, at least in some conditions, dogs as well as wolves preferentially approached a human partner who could see them in contrast to one whose eyes were occluded, and Udell et al. concluded that this success was dependent on the subjects' experiences with the specific occluder used. Here we argue, however, that since both partners expressed similar attentiveness towards the subjects by calling their names, Udell and colleagues' conclusion does not refer to the sensitivity of canines to others' attentiveness, but instead reflects the fact that the animals obeyed a familiar command better in a familiar context than in an unfamiliar one. Moreover, in contrast to Udell et al.'s conclusion, we believe that their data demonstrate that pet dogs can generalize the use of the visibility of human eyes to novel situations, showing a preference towards an attentive partner even if the eyes of the other partner are occluded in a novel way (e.g., having a bucket on his or her head). Finally, after presenting alternative interpretations of the results of the wolves tested by Udell and colleagues, we conclude that there is no evidence that wolves are sensitive to the attentional states of humans.}, } @article {pmid21771312, year = {2011}, author = {Lazzeri, G and Pammolli, A and Pilato, V and Giacchi, MV}, title = {Relationship between 8/9-yr-old school children BMI, parents' BMI and educational level: a cross sectional survey.}, journal = {Nutrition journal}, volume = {10}, number = {}, pages = {76}, pmid = {21771312}, issn = {1475-2891}, mesh = {Body Composition ; *Body Mass Index ; Body Weight ; Child ; Cross-Sectional Studies ; Educational Status ; Female ; Humans ; Italy/epidemiology ; Male ; Nutritional Status ; Obesity/*epidemiology ; *Parents ; Prevalence ; Risk Factors ; *Schools ; Socioeconomic Factors ; Surveys and Questionnaires ; }, abstract = {BACKGROUND: Parents are responsible not only for the genetic structure of their children, but also for passing onto them their behaviours and attitudes toward life. The aim of this study was to analyse the connection between school-age children's obesity and that of their parents as well as between child obesity and parents' educational level, as a proxy indicator of the socio-economic status (SES) of families in Tuscany.

METHODS: The children sample was selected from "OKkio alla Salute 2010" (a cross sectional survey carried out by the Italian Institute of Health) and consisted of 1,751 (922 males and 855 females) 8-9 year-old school children. Weight and height were measured by ad hoc trained personnel, and Body Mass Index (BMI) categories were calculated using Cole et al.'s cut-off. Parents' weight, height and educational level were collected by a self-administered questionnaire. The educational levels were classified as high, medium and low.

RESULTS: The prevalence of obese children increased along the parents' BMI category: from 1.4% for underweight mothers to 30.3% for obese mothers and from 4% for under-normal-weight fathers to 23.9% for obese fathers (p < 0.001). An inverse relationship was observed between the parents' educational level and child obesity, the lowest educational level corresponding to the highest prevalence of obese children: 9.3% for mothers with a low educational level compared to 5.8% for mothers with a high educational level (p = 0.15); similarly, the corresponding prevalence for fathers was 9.5% compared to 4.5% (p = 0.03).

CONCLUSION: Parents' obesity and the cultural resources of the family, particularly the father's, seem to influence the prevalence of overweight and obesity in Tuscan children.}, } @article {pmid21763664, year = {2011}, author = {Motzkus, C and Gensdarmes, F and Géhin, E}, title = {Study of the coalescence/splash threshold of droplet impact on liquid films and its relevance in assessing airborne particle release.}, journal = {Journal of colloid and interface science}, volume = {362}, number = {2}, pages = {540-552}, doi = {10.1016/j.jcis.2011.06.031}, pmid = {21763664}, issn = {1095-7103}, mesh = {Particle Size ; Particulate Matter/*analysis ; Surface Properties ; Surface Tension ; }, abstract = {Impingement of droplets on surfaces occurs in many industrial and natural processes. The study of droplet break-up is fundamental in order to determine the potential sources of airborne contamination for scenarios of hazardous liquid falls such as dripping. There are very few data in the literature describing the case of impact of millimetre-size droplets. The purposes of this work were to study experimentally particle emission during the impact of droplets on a liquid film and to assess the use of coalescence/splash relations to predict airborne particle release. The results are described using dimensionless numbers taking into account the inertial, viscosity and surface tension forces. Experiments were carried out for Weber numbers between 62 and 1754 and for Ohnesorge numbers between 2.0×10(-3) and 1.5×10(-2). New results on coalescence/splash thresholds are obtained using highly sensitive aerosol measurement and allow a prediction concerning the presence or absence of airborne particles according to a threshold relation. Moreover, we propose a modification of the Cossali et al.'s relation in order to describe the coalescence/prompt splash threshold.}, } @article {pmid21755103, year = {2010}, author = {Flórez-Torres, IE and Montalvo-Prieto, A and Herrera-Lían, A and Romero-Massa, E}, title = {[Effects on welfare of children and adults with chronic disease caregivers].}, journal = {Revista de salud publica (Bogota, Colombia)}, volume = {12}, number = {5}, pages = {754-764}, doi = {10.1590/s0124-00642010000500006}, pmid = {21755103}, issn = {2539-3596}, mesh = {Adolescent ; Adult ; *Caregivers ; Child ; Chronic Disease/*nursing ; Cross-Sectional Studies ; Female ; Humans ; Male ; Middle Aged ; *Quality of Life ; Young Adult ; }, abstract = {OBJECTIVE: Comparing the quality of caregivers' lives when they are related to child and adult patients suffering from chronic diseases (Cartagena, Colombia).

METHOD: This cross-sectional study was carried out on 91 child and 97 adult patient caregivers in three hospitals located in Cartagena, Colombia. Ferrell et al.'s psychometric test was used for ascertaining social well-being. Student's t-test was used for testing the effect of care-giving on physical, psychological, social and spiritual well-being.

RESULTS: Females aged 18 to 59 predominated as caregivers in both groups. The percentage of child caregivers who had not completed primary school was higher than that of those looking after adults. Psychological and social welfare was most affected in stroke care-givers (48.7 cf 50.5 (T<0.05) and 21.8 cf 19.2 (T <0.05), respectively). Child caregivers were significantly more affected than adult caregivers regarding spiritual welfare (23.7 cf 22.6 (T<0.05)). There was no significant difference regarding physical wellbeing (10.5 cf 11.1 (T>0.05)).

CONCLUSIONS: The experience of care-giving significantly modified people's perception of others' quality of life. Caregivers as an important source of informal care require health system support, particularly from nurses.}, } @article {pmid21748422, year = {2011}, author = {Lagroix, HE and Spalek, TM and Di Lollo, V}, title = {The role of observer strategy in the single-target AB paradigm.}, journal = {Psychonomic bulletin & review}, volume = {18}, number = {5}, pages = {917-922}, pmid = {21748422}, issn = {1531-5320}, mesh = {*Attention ; Attentional Blink ; Executive Function ; Humans ; *Pattern Recognition, Visual ; Photic Stimulation ; Psychomotor Performance ; }, abstract = {Identification of the second of two targets (T1, T2) inserted in a stream of distractors is impaired when presented 200-500 ms after the first (attentional blink, AB). An AB-like effect has been reported by Nieuwenstein, Potter, and Theeuwes, Journal of Experimental Psychology: Human Perception and Performance, 35, 159-169, (2009, Experiment 2), with a distractor stream that contained only one target and a gap just before the target. Nieuwenstein et al. hypothesized that the gap enhanced the salience of the last distractor, causing it to be processed much like T1 in conventional AB studies. This hypothesis can also account for Lag-1 sparing (enhanced target performance when presented directly after the last distractor, without an intervening gap). We propose an alternative account of the Lag-1 sparing in the single-target paradigm based on observer strategy, and test it by presenting the single-target and dual-target conditions to separate groups (Experiment 2) instead of mixed across trials (Experiment 1 and Nieuwenstein et al.'s study). The single-target condition exhibited Lag-1 sparing when it was mixed with the dual-target condition, but Lag-1 deficit when it was done in isolation. This outcome is consistent with an observer-strategy account but not with an enhanced salience account of the Lag-1 sparing effect in the single-target condition.}, } @article {pmid21744948, year = {2012}, author = {Belsky, J and Schlomer, GL and Ellis, BJ}, title = {Beyond cumulative risk: distinguishing harshness and unpredictability as determinants of parenting and early life history strategy.}, journal = {Developmental psychology}, volume = {48}, number = {3}, pages = {662-673}, doi = {10.1037/a0024454}, pmid = {21744948}, issn = {1939-0599}, mesh = {Child ; Child Abuse/*psychology ; Child Development ; Child, Preschool ; *Environment ; Female ; Humans ; Infant ; Longitudinal Studies ; Male ; Maternal Behavior/psychology ; Models, Psychological ; *Mother-Child Relations ; *Parenting ; Statistics as Topic ; United States ; }, abstract = {Drawing on life history theory, Ellis and associates' (2009) recent across- and within-species analysis of ecological effects on reproductive development highlighted two fundamental dimensions of environmental variation and influence: harshness and unpredictability. To evaluate the unique contributions of these factors, the authors of present article examined data from a national sample 1364 mothers and their children participating in the NICHD Study of Early Child Care and Youth Development. Harshness was operationalized as income-to-needs ratio in the first 5 years of life; unpredictability was indexed by residential changes, paternal transitions, and parental job changes during this same period. Here the proposition was tested that these factors not only uniquely predict accelerated life-history strategy, operationalized in terms of sexual behavior at age 15, but that such effects are mediated by change over the early-childhood years in maternal depression and, thereby, observed maternal sensitivity in the early-elementary-school years. Structural equation modeling provided empirical support for Ellis et al.'s (2009) theorizing, calling attention once again to the contribution of evolutionary analysis to understanding contemporary human parenting and development. Implications of the findings for intervention are discussed.}, } @article {pmid21735951, year = {2011}, author = {Khoja, T and Neyaz, Y and Qureshi, NA and Magzoub, MA and Haycox, A and Walley, T}, title = {Medication errors in primary care in Riyadh City, Saudi Arabia.}, journal = {Eastern Mediterranean health journal = La revue de sante de la Mediterranee orientale = al-Majallah al-sihhiyah li-sharq al-mutawassit}, volume = {17}, number = {2}, pages = {156-159}, pmid = {21735951}, issn = {1020-3397}, mesh = {Cross-Sectional Studies ; Humans ; Medication Errors/*statistics & numerical data ; Primary Health Care/*statistics & numerical data ; Private Sector ; Public Sector ; Saudi Arabia ; }, abstract = {Medication errors can cause a variety of adverse drug events but are potentially preventable. This cross-sectional study analysed all medication prescriptions from 5 public and 5 private primary health care clinics in Riyadh city, collected by simple random sampling during 1 working day. Prescriptions for 2463 and 2836 drugs from public and private clinics respectively were examined for errors, which were analysed using Neville et al.'s classification of prescription errors. Prescribing errors were found on 990/5299 (18.7%) prescriptions. Both type B and type C errors (major and minor nuisance) were more often associated with prescriptions from public than private clinics. Type D errors (trivial) were significantly more likely to occur with private health sector prescriptions. Type A errors (potentially serious) were rare (8/5299 drugs; 0.15%) and the rate did not differ significantly between the 2 health sectors. The development of preventive strategies for avoiding prescription errors is crucial.}, } @article {pmid21731768, year = {2011}, author = {Kenyon, EJ and McEwen, GK and Callaway, H and Elgar, G}, title = {Functional analysis of conserved non-coding regions around the short stature hox gene (shox) in whole zebrafish embryos.}, journal = {PloS one}, volume = {6}, number = {6}, pages = {e21498}, pmid = {21731768}, issn = {1932-6203}, support = {MC_U117597141/MRC_/Medical Research Council/United Kingdom ; G0401138/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Amino Acid Sequence ; Animals ; Conserved Sequence/*genetics ; DNA, Intergenic/*genetics ; Embryo, Nonmammalian/*metabolism ; Enhancer Elements, Genetic/genetics ; Gene Expression Regulation, Developmental ; Genes, Duplicate/genetics ; Genetic Loci/genetics ; Green Fluorescent Proteins/metabolism ; Humans ; Molecular Sequence Data ; Sequence Alignment ; Takifugu/genetics ; Transcription Factors/chemistry/*genetics/metabolism ; Zebrafish/*embryology/*genetics ; Zebrafish Proteins/chemistry/*genetics/metabolism ; }, abstract = {BACKGROUND: Mutations in the SHOX gene are responsible for Leri-Weill Dyschondrosteosis, a disorder characterised by mesomelic limb shortening. Recent investigations into regulatory elements surrounding SHOX have shown that deletions of conserved non-coding elements (CNEs) downstream of the SHOX gene produce a phenotype indistinguishable from Leri-Weill Dyschondrosteosis. As this gene is not found in rodents, we used zebrafish as a model to characterise the expression pattern of the shox gene across the whole embryo and characterise the enhancer domains of different CNEs associated with this gene.

Expression of the shox gene in zebrafish was identified using in situ hybridization, with embryos showing expression in the blood, putative heart, hatching gland, brain pharyngeal arch, olfactory epithelium, and fin bud apical ectodermal ridge. By identifying sequences showing 65% identity over at least 40 nucleotides between Fugu, human, dog and opossum we uncovered 35 CNEs around the shox gene. These CNEs were compared with CNEs previously discovered by Sabherwal et al., resulting in the identification of smaller more deeply conserved sub-sequence. Sabherwal et al.'s CNEs were assayed for regulatory function in whole zebrafish embryos resulting in the identification of additional tissues under the regulatory control of these CNEs.

CONCLUSION/SIGNIFICANCE: Our results using whole zebrafish embryos have provided a more comprehensive picture of the expression pattern of the shox gene, and a better understanding of its regulation via deeply conserved noncoding elements. In particular, we identify additional tissues under the regulatory control of previously identified SHOX CNEs. We also demonstrate the importance of these CNEs in evolution by identifying duplicated shox CNEs and more deeply conserved sub-sequences within already identified CNEs.}, } @article {pmid21727299, year = {2011}, author = {Bray, SR and Martin Ginis, KA and Woodgate, J}, title = {Self-regulatory strength depletion and muscle-endurance performance: a test of the limited-strength model in older adults.}, journal = {Journal of aging and physical activity}, volume = {19}, number = {3}, pages = {177-188}, doi = {10.1123/japa.19.3.177}, pmid = {21727299}, issn = {1063-8652}, mesh = {Adaptation, Psychological ; Aged ; Central Nervous System/physiopathology ; Female ; Humans ; Isometric Contraction ; Male ; Mental Fatigue/etiology/*physiopathology/*psychology ; Muscle Strength ; Muscle, Skeletal/physiopathology ; *Physical Endurance ; Psychomotor Performance ; Quality of Life ; *Social Control, Informal ; *Task Performance and Analysis ; }, abstract = {Self-regulation consumes a form of strength or energy. The authors investigated aftereffects of self-regulation depletion on muscle-endurance performance in older adults. Participants (N = 61, mean age = 71) were randomized to a self-regulation-depletion or control group and completed 2 muscle-endurance performance tasks involving isometric handgrip squeezing that were separated by a cognitive-depletion task. The depletion group showed greater deterioration of muscle-endurance performance than controls, F(1, 59) = 7.31, p = .009. Results are comparable to those of younger adults in a similar study and support Baumeister et al.'s limited-strength model. Self-regulation may contribute to central-nervous-system fatigue; however, biological processes may allow aging muscle to offset depletion of self-regulatory resources affecting muscle-endurance performance.}, } @article {pmid21712237, year = {2011}, author = {Phillips, NG and Attard, RD and Ghannoum, O and Lewis, JD and Logan, BA and Tissue, DT}, title = {Impact of variable [CO2] and temperature on water transport structure-function relationships in Eucalyptus.}, journal = {Tree physiology}, volume = {31}, number = {9}, pages = {945-952}, doi = {10.1093/treephys/tpr049}, pmid = {21712237}, issn = {1758-4469}, mesh = {Biological Transport ; Carbon Dioxide/*metabolism ; Eucalyptus/*metabolism ; Greenhouse Effect ; Models, Biological ; Photosynthesis ; Plant Leaves/metabolism ; Plant Stomata ; Plant Transpiration ; Temperature ; Water/*metabolism ; Xylem/metabolism ; }, abstract = {Nearly 30 years ago, Whitehead and Jarvis and Whitehead et al. postulated an elegant mechanistic explanation for the observed relationship between tree hydraulic structure and function, hypothesizing that structural adjustments promote physiological homeostasis. To date, this framework has been nearly completely overlooked with regard to varying atmospheric carbon dioxide ([CO(2)]). Here, we evaluated Whitehead's hypothesis of leaf water potential (Ψ(l)) homeostasis in faster-growing (Eucalyptus saligna) and slower-growing (Eucalyptus sideroxylon) tree saplings grown under three [CO(2)] (pre-industrial, current and future) and two temperature (ambient and ambient + 4°C) treatments. We tested for relationships between physiological (stomatal conductance and Ψ(l)) and structural (leaf and sapwood areas (A(l), A(s)), height (h), xylem conductivity (k(s))) plant variables as a function of the [CO(2)] and temperature treatments to assess whether structural variables adjusted to maintain physiological homeostasis. Structural components (A(l), A(s), h) generally increased with [CO(2)] or temperature, while g(s) was negatively correlated with [CO(2)]. Contrary to Whitehead's hypothesis, Ψ(l) did not exhibit homeostasis in either species; elevated temperatures were associated with more negative Ψ(l) in faster-growing E. saligna, and less negative Ψ(l) in slower-growing E. sideroxylon. Moreover, individual structural variables were generally uncorrelated with Ψ(l). However, across both species, the integrated hydraulic property of leaf specific hydraulic conductance (K(l)) was positively correlated with an independent calculation of K(l) determined exclusively from leaf physiological variables. These results suggest that physiological homeostasis may not apply to saplings exposed to global change drivers including [CO(2)] and temperature. Nevertheless, Whitehead et al.'s formulation identified K(l) as a sensitive measure of plant structural-physiological co-variation across species.}, } @article {pmid21707131, year = {2011}, author = {Rohling, ML and Larrabee, GJ and Greiffenstein, MF and Ben-Porath, YS and Lees-Haley, P and Green, P and Greve, KW}, title = {A misleading review of response bias: comment on McGrath, Mitchell, Kim, and Hough (2010).}, journal = {Psychological bulletin}, volume = {137}, number = {4}, pages = {708-12; authors reply 713-5}, doi = {10.1037/a0023327}, pmid = {21707131}, issn = {1939-1455}, mesh = {Humans ; Psychological Tests/*statistics & numerical data ; Psychology/*statistics & numerical data ; Psychometrics/*statistics & numerical data ; }, abstract = {In the May 2010 issue of Psychological Bulletin, R. E. McGrath, M. Mitchell, B. H. Kim, and L. Hough published an article entitled "Evidence for Response Bias as a Source of Error Variance in Applied Assessment" (pp. 450-470). They argued that response bias indicators used in a variety of settings typically have insufficient data to support such use in everyday clinical practice. Furthermore, they claimed that despite 100 years of research into the use of response bias indicators, "a sufficient justification for [their] use… in applied settings remains elusive" (p. 450). We disagree with McGrath et al.'s conclusions. In fact, we assert that the relevant and voluminous literature that has addressed the issues of response bias substantiates validity of these indicators. In addition, we believe that response bias measures should be used in clinical and research settings on a regular basis. Finally, the empirical evidence for the use of response bias measures is strongest in clinical neuropsychology. We argue that McGrath et al.'s erroneous perspective on response bias measures is a result of 3 errors in their research methodology: (a) inclusion criteria for relevant studies that are too narrow; (b) errors in interpreting results of the empirical research they did include; (c) evidence of a confirmatory bias in selectively citing the literature, as evidence of moderation appears to have been overlooked. Finally, their acknowledging experts in the field who might have highlighted these errors prior to publication may have prevented critiques during the review process.}, } @article {pmid21692233, year = {2011}, author = {Gerardo, NM and Wilson, AC}, title = {The power of paired genomes.}, journal = {Molecular ecology}, volume = {20}, number = {10}, pages = {2038-2040}, doi = {10.1111/j.1365-294x.2011.05103.x}, pmid = {21692233}, issn = {1365-294X}, mesh = {Amino Acids, Essential/metabolism ; Animals ; Aphids/*metabolism/*microbiology ; Bacteria/*genetics/*growth & development/*metabolism ; Buchnera/genetics/metabolism/physiology ; Sequence Analysis, DNA ; Symbiosis/genetics/*physiology ; }, abstract = {Species interactions are fundamental to ecology. Classic studies of competition, predation, parasitism and mutualism between macroscopic organisms have provided a foundation for the discipline, but many of the most important and intimate ecological interactions are microscopic in scale. These microscopic interactions include those occurring between eukaryotic hosts and their microbial symbionts. Such symbioses, ubiquitous in nature, provide experimental challenges because the partners often cannot live outside the symbiosis. With respect to the symbionts, this precludes utilizing classical microbiological and genetic techniques that require in vitro cultivation. Genomics, however, has rapidly changed the study of symbioses. In this issue of Molecular Ecology, MacDonald et al. (2011), coupling symbiont whole-genome sequencing, experimental studies and metabolic modelling, provide novel insights into one of the best-studied symbioses, that between aphids and their obligate, nutrient-provisioning, intracellular bacteria, Buchnera aphidicola (Fig. 1). MacDonald and colleagues assessed variation in the ability of aphid–Buchnera pairs to thrive on artificial diets missing different amino acids. As shown previously (e.g. Wilkinson & Douglas 2003), aphid–Buchnera pairs can differ in their requirements for external sources of essential amino acids. Such phenotypic variation could result from differences in Buchnera’s amino acid biosynthetic capabilities or in the ability of aphids to interact with their symbionts. Whole-genome sequencing of the Buchnera genomes from four aphid lines with alternate nutritional phenotypes revealed that the environmental nutrients required by the aphid–Buchnera pairs could not be explained by sequence variation in the symbionts. Instead, a novel metabolic modelling approach suggested that much of the variation in nutritional phenotype could be explained by host variation in the capacity to provide necessary nutrient precursors to their symbionts. MacDonald et al.’s work complements a recent study by Vogel & Moran (2011), who through crossing experiments investigating the inheritance of a nutritional phenotype associated with a frameshift mutation in a Buchnera amino acid biosynthesis gene powerfully demonstrated that different host genotypes paired with the same symbiont genome could exhibit substantially different nutritional requirements.† Thus, while there is little doubt that Buchnera are evolutionarily central to the nutritional ecology of aphids, the current work by MacDonald et al. (2011) together with that of Vogel & Moran (2011) surprisingly demonstrates host dominance in defining and controlling the ecological niche of this particular symbiosis.}, } @article {pmid21687446, year = {2011}, author = {Ihrke, M and Brennen, T}, title = {Sharing One Biographical Detail Elicits Priming between Famous Names: Empirical and Computational Approaches.}, journal = {Frontiers in psychology}, volume = {2}, number = {}, pages = {75}, pmid = {21687446}, issn = {1664-1078}, abstract = {In this paper three experiments and corresponding model simulations are reported that investigate the priming of famous name recognition in order to explore the structure of the part of the semantic system dealing with people. Consistent with empirical findings, novel computational simulations using Burton et al.'s interactive activation and competition model point to a conceptual distinction between how priming is initiated in single- and double-familiarity tasks, indicating that priming should be weaker or non-existent for the single-familiarity task. Experiment 1 demonstrates that, within a double-familiarity framework using famous names, categorical, and associative priming are reliable effects. Pushing the model to the limit, it predicts that pairs of celebrities who are neither associatively nor categorically related but who share single biographical features, both died in a car crash for example, should prime each other. Experiment 2 investigated this in a double-familiarity task but the effect was not observed. We therefore simulated and realized a pairwise learning task that was conceptually similar to the double-familiarity-decision task but allowed to strengthen the underlying connections. Priming based on a single biographical feature could be found both in simulations and the experiment. The effect was not due to visual or name similarity which were controlled for and participants did not report using the biographical links between the people to learn the pairs. The results are interpreted to lend further support to structural models of the memory for persons. Furthermore, the results are consistent with the idea that episodic features known about people are stored in semantic memory and are automatically activated when encountering that person.}, } @article {pmid21663975, year = {2011}, author = {Fonseca-Pedrero, E and Paino, M and Lemos-Giráldez, S and Sierra-Baigrie, S and Muñiz, J}, title = {Measurement invariance of the Schizotypal Personality Questionnaire-Brief across gender and age.}, journal = {Psychiatry research}, volume = {190}, number = {2-3}, pages = {309-315}, doi = {10.1016/j.psychres.2011.05.021}, pmid = {21663975}, issn = {0165-1781}, mesh = {Adolescent ; Adult ; Age Factors ; Child ; Factor Analysis, Statistical ; Female ; Humans ; Male ; *Psychiatric Status Rating Scales ; Reproducibility of Results ; Schizotypal Personality Disorder/*diagnosis ; Sex Factors ; *Surveys and Questionnaires ; Young Adult ; }, abstract = {The purpose of this study was to examine the dimensional structure and measurement invariance of the Schizotypal Personality Questionnaire-Brief (SPQ-B) (Raine and Benishay, 1995) across sex and age in a representative sample of nonclinical adolescents and young adults. The sample consisted of 1789 adolescents and young adults (42.1% males), with a mean age of 17.1years (S.D.=2.9). The results indicated that the Likert version of the SPQ-B showed adequate psychometric properties (α total score 0.89). The schizotypal personality models that presented the best fit indices were Raine et al.'s (1994) three-factor model and Stefanis et al.'s (2004) four-factor model. In addition, the results support the measurement invariance of the SPQ-B across sex and age. When the latent means of the schizotypal dimensions were compared across sex and age, statistically significant differences were found. Consistent with previous literature, schizotypal personality is a multidimensional construct whose structure appears invariant across sex and age. Future studies should examine the invariance of schizotypal personality across cultures, as well as using the SPQ-B as a screening method in the general population to detect individuals at risk for schizophrenia-spectrum disorders, given its rapid and easy administration.}, } @article {pmid21657808, year = {2011}, author = {Becker, RV and Dembek, C}, title = {Effects of cohort selection on the results of cost-effectiveness analysis of disease-modifying drugs for relapsing-remitting multiple sclerosis.}, journal = {Journal of managed care pharmacy : JMCP}, volume = {17}, number = {5}, pages = {377-381}, doi = {10.18553/jmcp.2011.17.5.377}, pmid = {21657808}, issn = {1944-706X}, mesh = {Clinical Trials as Topic/*methods ; Cohort Studies ; Cost-Benefit Analysis ; Decision Support Techniques ; *Drug Costs ; Glatiramer Acetate ; Humans ; Immunologic Factors/administration & dosage/economics/*therapeutic use ; Injections, Intramuscular ; Injections, Subcutaneous ; Interferon beta-1a ; Interferon beta-1b ; Interferon-beta/administration & dosage/economics/*therapeutic use ; Models, Economic ; Multiple Sclerosis, Relapsing-Remitting/*drug therapy/economics ; Patient Dropouts ; *Patient Selection ; Peptides/administration & dosage/economics/*therapeutic use ; Time Factors ; Treatment Outcome ; }, abstract = {BACKGROUND: Decision-analytic cost-effectiveness models are used to determine the most cost-effective treatment option on the basis of the best available data. Guidelines for pharmacoeconomic model development indicate that models should be updated as new evidence becomes available.

OBJECTIVE: To evaluate the appropriateness of the clinical data that were selected for Goldberg et al.'s 2009 model of cost-effectiveness in multiple sclerosis and calculate results based on a revised cohort selection method for intramuscular (IM) interferon (IFN) beta-1a.

METHODS: The original model compared cost per relapse avoided for IM IFN beta-1a, subcutaneous (SC) IFN beta-1a, IFN beta-1b, and glatiramer acetate (GA) based on intent-to-treat (ITT) results from clinical trials. However, due to lower-than-expected subject dropout rates, the IM IFN beta-1a trial had sufficient statistical power to be terminated early and was subsequently found to have met its primary endpoint, time to sustained 1.0-point Expanded Disability Status Scale progression. Within the "all-patient"(ITT) cohort (n=301), approximately 43% of patients were followed for less than 2 years; 172 patients were followed for 2 years or more. In contrast, the proportions of patients followed for at least 2 years in the clinical trials of IFN beta-1b, SC IFN beta-1a, and GA were 92%, 90%, and 86%, respectively. To test the impact of data selection on the cost-effectiveness model results, we recreated the original model using both the all-patient and 2-year cohorts from the IM IFN beta-1a pivotal trial. We then compared our results with those of the original model.

RESULTS: In the original model, costs per relapse avoided were $141,721 for IM IFN beta-1a, $80,589 for SC IFN beta-1a, $87,061 for SC IFN beta-1b, and $88,310 for GA. In the reanalysis using the 2-year completer data for IM IFN beta-1a, costs per relapse avoided were $77,980 for IM IFN beta-1a, $80,121 for SC IFN beta-1a, $86,572 for IFN beta-1b, and $87,767 for GA. The cost per relapse avoided for IM IFN beta-1a was approximately 45% lower than in the original analysis, whereas the recreated results for the other 3 therapies differed from the original results by less than 1%. Sensitivity analyses showed that the recreated model was robust and that the rank order of cost-effectiveness results was unaffected by changes to any univariate parameter.

CONCLUSIONS: The current study highlights the importance of data selection in cost-effectiveness analyses. After limiting the pivotal trial data for IM IFN beta-1a to patients followed for at least 2 years, we found that IM IFN beta-1a was more cost-effective than in the original analysis, while results for the other first-line disease-modifying drugs remained stable.}, } @article {pmid21647247, year = {2011}, author = {Aharoni, E and Antonenko, O and Kiehl, KA}, title = {Disparities in the moral intuitions of criminal offenders: The role of psychopathy.}, journal = {Journal of research in personality}, volume = {45}, number = {3}, pages = {322-327}, pmid = {21647247}, issn = {0092-6566}, support = {R01 DA026505/DA/NIDA NIH HHS/United States ; R01 MH070539/MH/NIMH NIH HHS/United States ; R01 MH085010/MH/NIMH NIH HHS/United States ; }, abstract = {The present study examined whether and in what ways psychopathy is associated with abnormal moral intuitions among criminal offenders. Using Haidt et al.'s Moral Foundations Questionnaire, 222 adult male offenders assessed for clinical psychopathy reported their degree of support for five moral domains: Harm Prevention, Fairness, Respect for Authority, Ingroup Loyalty, and Purity/Sanctity. As predicted, psychopathy total score explained a substantial proportion of the variance in reduced support for Harm Prevention and Fairness, but not the other domains. These results confirm that psychopathy entails a discrete set of moral abnormalities and suggest that these abnormalities could potentially help to explain the characteristic antisocial behavior of individuals with psychopathy.}, } @article {pmid21639015, year = {2011}, author = {Sougleris, C and Ranzijn, R}, title = {Proactive coping in community-dwelling older Australians.}, journal = {International journal of aging & human development}, volume = {72}, number = {2}, pages = {155-168}, doi = {10.2190/AG.72.2.d}, pmid = {21639015}, issn = {0091-4150}, mesh = {*Adaptation, Psychological ; Aged ; Aged, 80 and over ; Aging/*psychology ; Australia ; Female ; Humans ; Male ; *Mental Health ; Predictive Value of Tests ; *Quality of Life ; Regression Analysis ; Residence Characteristics ; Surveys and Questionnaires ; }, abstract = {This article reports on a study of older community-dwelling Australian adults which aimed to test whether a relatively unexplored construct, proactive coping, could have a role in purpose in life, personal growth, and life satisfaction. A total of 109 women and 115 men (Mean age = 75.04 yrs, SD = 6.66) completed a questionnaire containing Greenglass et al.'s (1999) Proactive Coping Inventory, the Purpose in Life and Personal Growth subscales of Ryff's (1989) Psychological Well-being Scales, and the Satisfaction with Life Scale (Diener et al., 1985). The results of hierarchical multiple regression analyses indicated that proactive coping was a highly significant predictor of all three measures of well-being, after controlling for age and health. The effect on personal growth and purpose in life was particularly strong. Proactive coping does seem to be an important variable in the psychological well-being of older adults. However, the correlational nature of the design, and the likelihood of some conceptual overlap between the well-being variables, suggest that these inferences can only be tentative. Designing psychological interventions to improve proactive coping may help to improve quality of life at older ages. There is a need for experimental research to further explore the causal influence of proactive coping and for further theoretical work to determine the exact nature of proactive coping.}, } @article {pmid21627763, year = {2011}, author = {Green, TC and Zaller, N and Rich, J and Bowman, S and Friedmann, P}, title = {Revisiting Paulozzi et al.'s "Prescription drug monitoring programs and death rates from drug overdose".}, journal = {Pain medicine (Malden, Mass.)}, volume = {12}, number = {6}, pages = {982-985}, doi = {10.1111/j.1526-4637.2011.01136.x}, pmid = {21627763}, issn = {1526-4637}, support = {K24DA022112/DA/NIDA NIH HHS/United States ; R21CE001846-01/CE/NCIPC CDC HHS/United States ; }, mesh = {Analgesics, Opioid/*poisoning ; Drug Monitoring/*methods ; Drug Overdose/*mortality ; Humans ; Prescription Drugs/*poisoning ; }, } @article {pmid21626301, year = {2011}, author = {Iwamasa, GY and Iwasaki, M}, title = {A new multidimensional model of successful aging: perceptions of Japanese American older adults.}, journal = {Journal of cross-cultural gerontology}, volume = {26}, number = {3}, pages = {261-278}, pmid = {21626301}, issn = {1573-0719}, mesh = {Activities of Daily Living ; Aged ; Asian/*psychology ; Attitude to Health ; Female ; Focus Groups ; Geriatric Assessment/*methods ; *Health Status ; Humans ; Male ; Middle Aged ; Models, Psychological ; *Personal Satisfaction ; *Quality of Life ; Self-Assessment ; Social Values ; *Spirituality ; Surveys and Questionnaires ; }, abstract = {This study examined the concept of successful aging using an ethnographic grounded-theory approach. Seventy-seven Japanese American older adults participated in focus groups. Participants perceived successful aging as optimal functioning in the following areas: Physical health, psychological health, cognitive functioning, socialization, spirituality, and financial security. The content of each dimension represents both culture-specific and culturally-universal elements. This new multidimensional model of successful aging was compared to Rowe and Kahn's (The Gerontologist 37:433-440, 1997) and Phelan et al.'s frameworks (Journal of the American Geriatric Society 52:211-216, 2004) of successful aging. The model of successful aging generated from this study appears to be more comprehensive than existing models and incorporates sociocultural experiences.}, } @article {pmid21621398, year = {2011}, author = {Wiącek, AE}, title = {Changes in wetting properties of alumina surface treated with DPPC in the presence of phospholipase A2 enzyme.}, journal = {Colloids and surfaces. B, Biointerfaces}, volume = {87}, number = {1}, pages = {54-60}, doi = {10.1016/j.colsurfb.2011.04.035}, pmid = {21621398}, issn = {1873-4367}, mesh = {1,2-Dipalmitoylphosphatidylcholine/*pharmacology ; Aluminum Oxide/*chemistry ; Animals ; Formamides/chemistry ; Octanes/chemistry ; Particle Size ; Phospholipases A2/*pharmacology ; Sodium Chloride/chemistry ; Thermodynamics ; Time Factors ; Volatilization/drug effects ; Wettability/drug effects ; }, abstract = {Wetting properties of commercial Al(2)O(3) plates contacted with dipalmitoylphosphatidylcholine (DPPC) or DPPC+enzyme (phospholipase PLA(2)) in NaCl solution were determined by thin layer wicking and with the help of Washburn equation. Van Oss et al.'s approach to interfacial free energy interactions was applied to determining the solid surface free energy components. Wicking experiments were performed both for bare and alumina plates precontacted overnight with the probe liquid saturated vapours, as well as the untreated and DPPC (or DPPC+PLA(2)) treated alumina plates. For this purpose the penetration rates of n-octane, water and formamide were measured. From these experiments it resulted that original alumina surface is strongly polar with electron-donor interactions originating from the surface hydroxyl groups. Adsorption of DPPC on Al(2)O(3) plates slightly increased the hydrophobic character of the alumina surface (considerable decrease of the electron-donor, γ(s)(-) parameter and γ(s)(AB) component was visible) in such a way that the hydrocarbon chains were directed outwards and the polar part towards the alumina surface. However, after the enzyme action the products of DPPC hydrolysis by PLA(2) (palmitic acid and lysophosphatidylcholine) increased again the hydrophilic character of Al(2)O(3) surface (a minor increase in γ(s)(AB) component and drastic increase of the electron-donor γ(s)(-) parameter was noticeable). After treatment with DPPC or DPPC+enzyme PLA(2) solution the changes of the total surface free energy of alumina and its Lifshits-van der Waals (γ(s)(LW)) component were in the range 7-10 mJ/m(2), but the most considerable and delivering more interesting information were the changes of the electron-donor (γ(s)(-)) parameter ranging from 27 to 35 mJ/m(2). Moreover, the changes of the alumina surface wettability were dependent on the time of the enzyme contacting with DPPC in NaCl solution. On the basis of the obtained results it seems that the thin layer wicking method can be an additional useful tool in investigations of the effect of phospholipid and PLA(2) action on the hydrophilic-hydrophobic character of alumina surface.}, } @article {pmid21615405, year = {2012}, author = {van Bergen, E and de Jong, PF and Plakas, A and Maassen, B and van der Leij, A}, title = {Child and parental literacy levels within families with a history of dyslexia.}, journal = {Journal of child psychology and psychiatry, and allied disciplines}, volume = {53}, number = {1}, pages = {28-36}, doi = {10.1111/j.1469-7610.2011.02418.x}, pmid = {21615405}, issn = {1469-7610}, mesh = {Adult ; Analysis of Variance ; Child ; Cognition ; Dyslexia/*epidemiology ; *Educational Status ; Family Health/*statistics & numerical data ; Female ; Genetic Predisposition to Disease/epidemiology ; Humans ; Language Tests/statistics & numerical data ; Longitudinal Studies ; Male ; Netherlands/epidemiology ; *Parents ; Phonetics ; *Reading ; Risk Factors ; }, abstract = {BACKGROUND: The present study concerns literacy and its underlying cognitive skills in Dutch children who differ in familial risk (FR) for dyslexia. Previous studies with FR-children were inconclusive regarding the performance of FR-children without dyslexia as compared to the controls. Moreover, van Bergen et al. (2011) recently showed that FR-children with and without dyslexia differed in parental reading skills, suggesting that those who go on to develop dyslexia have a higher liability. The current study concerned 1) the comparison of three groups of children at the end of second grade and 2) the intergenerational transfer of reading and its underlying cognitive skills from parent to child.

METHOD: Three groups of children were studied at the end of second grade: FR-dyslexia (n = 42), FR-no-dyslexia (n = 99), and control children (n = 66). Parents and children were measured on naming, phonology, spelling, and word and pseudoword reading.

RESULTS: The FR-dyslexia children were severely impaired across all tasks. The FR-no-dyslexia children performed better than the FR-dyslexia children, but still below the level of the controls on all tasks; the only exception was rapid naming (RAN), on which they were as fast as the controls. Focusing on the FR subsample, parental reading and RAN were related to their offspring's reading status.

CONCLUSIONS: We replicated and extended van Bergen et al.'s study in showing that the FR-children who develop dyslexia are likely to have a higher liability. Both the group comparisons and the parent-child relations highlight the importance of good RAN skills for reading acquisition.}, } @article {pmid21600335, year = {2011}, author = {Bret, P and Heil, M and Queuille, E and Bret, MC and , }, title = {[Evaluation of prescription practices of long acting injectable risperidone in French hospitals].}, journal = {L'Encephale}, volume = {37 Suppl 1}, number = {}, pages = {S58-65}, doi = {10.1016/j.encep.2010.04.001}, pmid = {21600335}, issn = {0013-7006}, mesh = {Administration, Oral ; Adolescent ; Adult ; Aged ; Antipsychotic Agents/*administration & dosage/adverse effects ; Basal Ganglia Diseases/chemically induced ; Bipolar Disorder/*drug therapy ; Cohort Studies ; Delayed-Action Preparations ; Dose-Response Relationship, Drug ; Female ; Hospitalization ; Humans ; Injections, Intramuscular ; Male ; Middle Aged ; Patient Dropouts/statistics & numerical data ; Practice Patterns, Physicians'/*statistics & numerical data ; Prospective Studies ; Psychotic Disorders/*drug therapy ; Risperidone/*administration & dosage/adverse effects ; Young Adult ; }, abstract = {INTRODUCTION: Atypical antipsychotics or antipsychotics of second generation are still recommended by guidelines for primary use in the treatment of psychotic disorders because of their better neurologic safety and efficacy. However, they require daily dosing, thus compromising their overall efficacy whereas conventional depot neuroleptics provide constant pharmacologic treatment but induce extrapyramidal adverse effects and poor efficacy on negative symptoms. Long acting injectable risperidone (LAIR) is the first long-acting second-generation antipsychotic. Registered in October 2003 and launched in March 2005 in France thanks to Kane et al.'s and Fleischhacker et al.'s reference studies, it was supposed to provide the advantages of conventional long acting formulations of antipsychotics over those of an atypical agent.

OBJECTIVES AND METHODS: The aims of this study, with the description of the prescription practices of LAIR in naturalistic conditions, were to assess the place of this new drug in psychotic medication, with the efficiency value measured by treatment discontinuation rate and analysis of the reasons for discontinuation, and to assess whether the prescriptions practices are or not in adequacy with guidelines and reglementation. In June 2005, we conducted a one-year naturalistic non-randomised open-label study in nine French psychiatric hospitals, members of the PIC network: were included all the patients who received LAIR every 2 weeks, between July 1st 2005 and November 30th 2005.

RESULTS: Prescriptions of 216 patients were examined for 1 year. LAIR was used off label for 15% of the patients. Ninety-two percent of patients were hospitalized at the beginning of the treatment while 72% of the treated patients had dropped out one year after the first injection. Regarding the nature of previous antipsychotic treatments prescribed in the last three months before the first injection of LAIR: 31% patients had received a first generation antipsychotic, half of which had received a depot antipsychotic of first generation and 69% had received a second-generation antipsychotic, among which half had received oral risperidone. The principal reason noted by the clinicians for starting the new formulation was non-observance with anterior treatments. However, oral antipsychotic treatment preceding the first injection was used less than 4 weeks for one third of the patients. When this treatment was oral risperidone, average posology at the first injection was 6.7 ± 2.4 mg per day; it was 7.4 ± 2.1 mg per day for the patients who received the higher dose of LAIR (50 mg/2 weeks). So, it seems that some patients were not sufficiently stabilized by their antipsychotic before the beginning of the long acting treatment. The result was a significant rate of treatment discontinuations (53%) in the following year, principally caused by the withdrawal of the patient's consent and an insufficient response to treatment.

CONCLUSION: This investigation provided the opportunity to analyze the prescriptions of a new formulation drug in routine clinical practice. It confirms the need for respecting the authorized indications and the recommendations of good use of a drug to avoid the failures of treatment and also the importance of the role of the pharmacist in recalling it to the physicians.}, } @article {pmid21567657, year = {2012}, author = {Thatcher, RW and North, DM and Biver, CJ}, title = {Diffusion spectral imaging modules correlate with EEG LORETA neuroimaging modules.}, journal = {Human brain mapping}, volume = {33}, number = {5}, pages = {1062-1075}, pmid = {21567657}, issn = {1097-0193}, mesh = {Adolescent ; Adult ; Brain Mapping/*methods ; Electroencephalography/*methods ; Electromagnetic Fields ; Female ; Humans ; Image Processing, Computer-Assisted/*methods ; Male ; Nerve Net/*physiology ; Neuroimaging/*methods ; Young Adult ; }, abstract = {OBJECTIVES: The purpose of this study was to test the hypothesis that the highest temporal correlations between 3-dimensional EEG current source density corresponds to anatomical Modules of high synaptic connectivity.

METHODS: Eyes closed and eyes open EEG was recorded from 19 scalp locations with a linked ears reference from 71 subjects age 13-42 years. LORETA was computed from 1 to 30 Hz in 2,394 cortical gray matter voxels that were grouped into six anatomical Modules corresponding to the ROIs in the Hagmann et al.'s [2008] diffusion spectral imaging (DSI) study. All possible cross-correlations between voxels within a DSI Module were compared with the correlations between Modules.

RESULTS: The Hagmann et al. [ 2008] Module correlation structure was replicated in the correlation structure of EEG three-dimensional current source density.

CONCLUSIONS: EEG Temporal correlation between brain regions is related to synaptic density as measured by diffusion spectral imaging.}, } @article {pmid21560508, year = {2010}, author = {Whitt, HP}, title = {The civilizing process and its discontents: suicide and crimes against persons in France, 1825-1830.}, journal = {AJS; American journal of sociology}, volume = {116}, number = {1}, pages = {130-186}, doi = {10.1086/653541}, pmid = {21560508}, issn = {0002-9602}, mesh = {France ; History, 19th Century ; Homicide/*history ; Humans ; *Social Change ; Suicide/*history ; Violence/*history ; }, abstract = {A spatial analysis of data for French départements assembled in the 1830s by André-Michel Guerry and Adolphe d'Angeville examines the impacts of modernization and resistance to governmental "Frenchification" policies on measures of violence and its direction. In the context of Unnithan et al.'s integrated model of suicide and homicide, high suicide rates in the northern core and a predilection for violence against others in the southern periphery may be consistently interpreted in terms of theories of the civilizing process and internal colonialism. Alternative explanations of southern violence in 19th-century France are explored and rejected, and additional theoretical applications are suggested.}, } @article {pmid21526333, year = {2012}, author = {Wu, S and Chen, K}, title = {An efficient key-management scheme for hierarchical access control in e-medicine system.}, journal = {Journal of medical systems}, volume = {36}, number = {4}, pages = {2325-2337}, pmid = {21526333}, issn = {0148-5598}, mesh = {*Access to Information ; *Computer Security ; Humans ; *Internet ; Medical Records Systems, Computerized/*organization & administration ; Software Design ; }, abstract = {In e-medicine system, the sharing of patients' medical histories scattered among medical institutions through the Internet is highly desirable. The most immediate cryptographic need certainly is an efficient key management method to solve dynamic access problems in a user hierarchy. In this paper, we propose a practical solution for dynamic access problem in a user hierarchy based on hybrid cryptosystems. When compared with Nikooghadam et al.'s scheme proposed most recently, the time complexity and the required storage space is reduced significantly. Moreover, it provides provable security, and is easy to implement. Therefore, our scheme is more suitable for e-medicine system.}, } @article {pmid21521087, year = {2011}, author = {Zamorski, MA}, title = {Suicide prevention in military organizations.}, journal = {International review of psychiatry (Abingdon, England)}, volume = {23}, number = {2}, pages = {173-180}, doi = {10.3109/09540261.2011.562186}, pmid = {21521087}, issn = {1369-1627}, mesh = {Adult ; Humans ; Male ; Mental Disorders/*complications/etiology ; Mental Health Services/statistics & numerical data ; Middle Aged ; Military Personnel/*education/*psychology ; Military Psychiatry/trends ; Risk Factors ; Stress, Psychological/*complications ; Suicide/*psychology ; Young Adult ; *Suicide Prevention ; }, abstract = {Suicide is an important public health problem in the demographic group that forms the bulk of military populations, namely young and middle-aged men. Suicide in the military also has special significance: certain aspects of military service can lead to serious mental disorders that increase the risk of suicidal behaviour. Moreover, military organizations have control over a broad range of factors (notably the direct delivery of mental health care) that could mitigate suicide risk. This article will review the literature on suicide risk in military organizations to answer the important question: Are military personnel at increased risk for suicide? Next, Mann et al.'s (2005) model for specific suicide preventive interventions in civilian settings will be reviewed and then expanded, with an emphasis on identifying special opportunities for suicide prevention in military organizations, including: 1) organizational interventions to mitigate work stress; 2) selection, resilience training, and risk factor reduction; 3) interventions to overcome barriers to care; and 4) systematic quality improvement efforts in mental health care. Finally, the evidence behind comprehensive suicide prevention programmes will be reviewed, with a special focus on the US Air Force's benchmark programme.}, } @article {pmid21503645, year = {2011}, author = {Flouri, E and Panourgia, C}, title = {Adverse life events and emotional and behavioral problems in adolescence: the role of non-verbal cognitive ability and negative cognitive errors.}, journal = {Journal of abnormal child psychology}, volume = {39}, number = {5}, pages = {695-709}, pmid = {21503645}, issn = {1573-2835}, mesh = {Adolescent ; Affective Symptoms/etiology/*psychology ; Child Behavior Disorders/etiology/*psychology ; *Cognition ; Emotions ; Female ; Humans ; *Life Change Events ; Male ; Psychological Tests ; Verbal Behavior ; }, abstract = {The aim of this study was to test whether negative cognitive errors (overgeneralizing, catastrophizing, selective abstraction, and personalizing) mediate the moderator effect of non-verbal cognitive ability on the association between adverse life events (life stress) and emotional and behavioral problems in adolescence. The sample consisted of 430 children (aged 11-15 years) from three state secondary schools in disadvantaged areas in one county in the South East of England. Total difficulties (i.e., emotional symptoms, peer problems, hyperactivity, and conduct problems) were assessed with the Strengths and Difficulties Questionnaire. Adjustment was made for gender, age, ethnicity, special educational needs, exclusion history, family structure, and family socio-economic disadvantage. Adverse life events were measured with Tiet et al.'s (Journal of the American Academy of Child & Adolescent Psychiatry, 37, 1191-1200, 1998) Adverse Life Events Scale. Non-verbal cognitive ability was measured with Raven's Standard Progressive Matrices Plus. Non-verbal cognitive ability moderated the effect of adverse life events both on total difficulties and on emotional symptoms. Overgeneralizing mediated the moderator effect of non-verbal cognitive ability on the association between adverse life events and total difficulties. Adverse life events were related to a tendency to overgeneralize which was associated with emotional and behavioral problems, but particularly among those adolescents with lower non-verbal cognitive ability.}, } @article {pmid21502743, year = {2011}, author = {Chauvet, A and Dewilde, A and Thomas, D and Joriot, S and Vaast, P and Houfflin-Debarge, V and Subtil, D}, title = {Ultrasound diagnosis, management and prognosis in a consecutive series of 27 cases of fetal hydrops following maternal parvovirus B19 infection.}, journal = {Fetal diagnosis and therapy}, volume = {30}, number = {1}, pages = {41-47}, doi = {10.1159/000323821}, pmid = {21502743}, issn = {1421-9964}, mesh = {Erythema Infectiosum/*complications/diagnostic imaging/virology ; Female ; Humans ; Hydrops Fetalis/diagnostic imaging/*virology ; Pregnancy ; Pregnancy Complications, Infectious/*diagnostic imaging ; Prognosis ; Retrospective Studies ; Ultrasonography, Prenatal ; }, abstract = {INTRODUCTION: Fetal hydrops caused by anemia from parvovirus B19 infection (FH-B19) is rare. Doppler measurement of the middle cerebral artery peak systolic velocity (PSV-MCA) improves its prenatal diagnosis, but its frequency and prognosis are still poorly known. Despite improved survival due to in utero transfusions, the possibility of late neurological sequelae makes prognosis uncertain.

OBJECTIVES: To assess the frequency, management and prognosis of a consecutive series of FH-B19 observed over a 15-year period.

METHODS: Retrospective study of 27 cases of FH-B19, that is, 3/100,000 births, 24 of them discovered during routine second-trimester ultrasound. All but 1 case (96.2%) had at least four of the six ultrasound signs that Saltzman et al. [Obstet Gynecol 1989;74:106-111] suggested as indicators of anemia. Of the fetuses tested, 80% had a PSV-MCA >1.5 MoM, also indicative of anemia. Of the 19 fetuses treated by exchange transfusions, 11 were liveborn compared with 2 of the 6 not so treated (57.8 vs. 33.3%, NS). The survival rate was higher during the second half of the study period (23.1 vs. 71.4%, p < 0.02) for less severe anemia (p < 0.03) and for repeated transfusions (p = 0.03). In our series, 1 case of prenatal cerebral atrophy was identified on screening. All 13 liveborn children appeared healthy at the age of 1 year.

CONCLUSION: In cases of fetal hydrops, Saltzman et al.'s ultrasound criteria and PSV-MCA measurement made it possible to determine the likelihood that anemia is the cause of the hydrops and to measure its intensity. Use of these techniques allowed us to choose the most appropriate treatment (transfusion or not, depending on the degree of anemia), and survival improved notably in our series.}, } @article {pmid23687441, year = {2011}, author = {Marchand, A and Beaulieu-Prévost, D and Guay, S and Bouchard, S and Drouin, MS and Germain, V}, title = {Relative Efficacy of Cognitive-Behavioral Therapy Administered by Videoconference for Posttraumatic Stress Disorder: A Six-Month Follow-Up.}, journal = {Journal of aggression, maltreatment & trauma}, volume = {20}, number = {3}, pages = {304-321}, pmid = {23687441}, issn = {1092-6771}, support = {110341-1/CAPMC/CIHR/Canada ; 110341-1//PHS HHS/United States ; }, abstract = {Until recently, only one study was published on cognitive-behavioral therapy (CBT) of posttraumatic stress disorder (PTSD) in individual therapy via videoconference (Germain, Marchand, Bouchard, Drouin, & Guay, 2009); however, it only assessed the posttreatment effect. This study presents the follow-up of Germain et al.'s (2009) study. The main goal was to compare the effectiveness after six months of CBT for PTSD either face-to-face (n = 24) or by videoconference (n = 12). Each participant received CBT for 16 to 25 weeks and completed various questionnaires before and after treatment and at a six-month follow-up. The two treatments had equivalent levels of symptom reduction (Modified PTSD Symptom Scale: η[2] < 0.01, p > .05) and proportion of patients with a clinically significant change in symptoms (42% for face-to-face vs. 38% for videoconferencing, p > .05). Thus, CBT for PTSD via videoconference seems to be a viable alternative when adequate face-to-face treatments are less available.}, } @article {pmid21480757, year = {2011}, author = {Love, J and McKoon, G}, title = {Rules of engagement: incomplete and complete pronoun resolution.}, journal = {Journal of experimental psychology. Learning, memory, and cognition}, volume = {37}, number = {4}, pages = {874-887}, pmid = {21480757}, issn = {1939-1285}, support = {R01 DC001240/DC/NIDCD NIH HHS/United States ; R01-DC01240/DC/NIDCD NIH HHS/United States ; }, mesh = {Attention/physiology ; Comprehension/*physiology ; Concept Formation ; Female ; Humans ; *Language ; Male ; Probability ; Psycholinguistics ; Reaction Time/physiology ; *Reading ; Recognition, Psychology/*physiology ; Reference Values ; Students ; Universities ; }, abstract = {Research on shallow processing suggests that readers sometimes encode only a superficial representation of a text and fail to make use of all available information. Greene, McKoon, and Ratcliff (1992) extended this work to pronouns, finding evidence that readers sometimes fail to automatically identify referents even when these are unambiguous. In this paper we revisit those findings. In 11 recognition probe, priming, and self-report experiments, we manipulated Greene et al.'s stories to discover under what circumstances a pronoun's referent is automatically understood. We lengthened the stories from 4 to 8 lines. This simple manipulation led to automatic and correct resolution, which we attribute to readers' increased engagement with the stories. We found evidence of resolution even when the additional text did not mention the pronoun's referent. In addition, our results suggest that the pronoun temporarily boosts the referent's accessibility, an advantage that disappears by the end of the next sentence. Finally, we present evidence from memory experiments that supports complete pronoun resolution for the longer but not the shorter stories.}, } @article {pmid21469002, year = {2012}, author = {Makris, E and Gkanis, V and Tsangaris, S and Housiadas, C}, title = {A methodology to generate structured computational grids from DICOM data: application to a patient-specific abdominal aortic aneurysm (AAA) model.}, journal = {Computer methods in biomechanics and biomedical engineering}, volume = {15}, number = {2}, pages = {173-183}, doi = {10.1080/10255842.2010.518963}, pmid = {21469002}, issn = {1476-8259}, mesh = {Aortic Aneurysm, Abdominal/*pathology ; Humans ; *Models, Biological ; }, abstract = {This study presents the generation of a multi-block structured grid on a real abdominal aortic aneurysm (AAA) acquired from Digital Imaging and Communication in Medicine (DICOM) data. With the use of a computed tomography exam (or medical images in standard DICOM format), the shape of a human organ is extracted and a structured computational grid is created. The structured grid generation is done by utilising Floater's and Gopalsamy et al.'s algorithm. The proposed methodology is applied to the AAA case, but it may also be applied to other human organs, enabling the scientist to develop an advanced patient-specific model. More importantly, the proposed methodology provides a precise reconstruction of the human organs, which is required in an AAA, where small variations in the geometry may alter the flow field, the stresses exerted on the walls and finally the rupture risk of the aneurysm.}, } @article {pmid21463029, year = {2011}, author = {Miller, MJ and Sendrowitz, K}, title = {Counseling psychology trainees' social justice interest and commitment.}, journal = {Journal of counseling psychology}, volume = {58}, number = {2}, pages = {159-169}, doi = {10.1037/a0022663}, pmid = {21463029}, issn = {0022-0167}, mesh = {Adult ; Counseling/*education/*ethics ; Education, Graduate/*ethics/methods ; Female ; Humans ; Male ; *Morals ; *Motivation ; *Social Justice ; }, abstract = {Scholars within the field of counseling psychology have for some time now articulated eloquent and compelling calls for attending to social justice in the social sciences. To date, counseling psychologists have been at the forefront of addressing social justice issues in research, practice, and professional development. The present study advances empirical perspectives on social justice by testing the external validity of M. J. Miller et al.'s (2009) social-cognitive model of social justice interest and commitment in a sample of 229 doctoral trainees in counseling psychology. Present findings support the ability of the model to explain, in part, counseling psychology trainees' social justice interest and commitment. In addition, the present study provides novel findings that demonstrate the direct and indirect ways in which program training environment and personal moral imperative relate to social justice interest and commitment. Study limitations, future directions for research, and implications for training are discussed.}, } @article {pmid21457477, year = {2011}, author = {Greenstone, MH and Vandenberg, NJ and Hu, JH}, title = {Barcode haplotype variation in north American agroecosystem lady beetles (Coleoptera: Coccinellidae).}, journal = {Molecular ecology resources}, volume = {11}, number = {4}, pages = {629-637}, doi = {10.1111/j.1755-0998.2011.03007.x}, pmid = {21457477}, issn = {1755-0998}, mesh = {Animals ; Cluster Analysis ; Coleoptera/*classification/*genetics ; DNA Barcoding, Taxonomic ; DNA Primers/genetics ; DNA, Mitochondrial/chemistry/genetics ; Electron Transport Complex IV/genetics ; *Haplotypes ; Molecular Sequence Data ; Phylogeny ; *Polymorphism, Genetic ; Sequence Homology ; United States ; }, abstract = {DNA barcodes have proven invaluable in identifying and distinguishing insect pests, most notably for determining the provenance of exotic invasives, but relatively few insect natural enemies have been barcoded. We used Folmer et al.'s (1994) universal invertebrate primers and Hebert et al.'s (2004) for Lepidoptera, to amplify 658 bp at the 5' end of the mitochondrial cytochrome oxidase c subunit I (COI) gene in five species of lady beetles from crop fields in six states in the US Mid-Atlantic, Plains and Midwest: three native species, Hippodamia convergens Guérin-Méneville, H. parenthesis (Say) and Coleomegilla maculata (De Geer); and two exotic species, Harmonia axyridis (Pallas) and Coccinella septempunctata Linnaeus. Sequence divergences within species were low, never exceeding 0.9% (Kimura 2-parameter distances). Sequence divergences between the two Hippodamia species ranged from 14.7 to 16.4%, mirroring the relationships found for other arthropod taxa. Among the exotic species, C. septempunctata sequences were as variable as those of the three native species, while H. axyridis populations comprised a single haplotype. Limited data on two Coleomegilla subspecies, C. m. lengi Timberlake and C. m. fuscilabris (Mulsant), are consistent with their belonging to the same species, although morphological and reproductive data indicate that they represent separate species. Our results support the general utility of COI barcodes for distinguishing and diagnosing coccinellid species, but point to possible limitations in the use of barcodes to resolve species assignments in recently divergent sibling species.}, } @article {pmid21457170, year = {2011}, author = {Rousset, F and Lion, S}, title = {Much ado about nothing: Nowak et al.'s charge against inclusive fitness theory.}, journal = {Journal of evolutionary biology}, volume = {24}, number = {6}, pages = {1386-1392}, doi = {10.1111/j.1420-9101.2011.02251.x}, pmid = {21457170}, issn = {1420-9101}, mesh = {Animals ; Behavior, Animal/*physiology ; Biological Evolution ; *Models, Biological ; *Publishing ; Selection, Genetic ; *Social Behavior ; }, abstract = {In a recent article, Nowak et al. claim that the mathematical basis of inclusive fitness theory does not stand to scrunity and to have found an alternative explanation for eusociality. We show that these claims are based on false premises, many of which have been exposed more than 25 years ago, such as misrepresentations of the basic components of inclusive fitness and fallacious distinctions between individual fitness and inclusive fitness. Moreover, some limitations ascribed to inclusive fitness are actually limitations of current evolutionary theory, for which Nowak et al. propose no new solution. Likewise, their assertedly 'common sense' empirical alternative to estimating inclusive fitness is not applicable in cases of interest. Finally, their eusociality model merely confirms the importance of all the components of inclusive fitness. We conclude by discussing how rhetorical devices and editorial practices can impede scientific endeavours.}, } @article {pmid21442001, year = {2011}, author = {Callahan, BG}, title = {Commentary on Watson et al.'s Articles on Airport Remediation Following a Chemical Terrorist Attack.}, journal = {Human and ecological risk assessment : HERA}, volume = {17}, number = {1}, pages = {122-123}, pmid = {21442001}, issn = {1080-7039}, } @article {pmid21387460, year = {2011}, author = {May, H and Peled, N and Dar, G and Abbas, J and Hershkovitz, I}, title = {Hyperostosis frontalis interna: what does it tell us about our health?.}, journal = {American journal of human biology : the official journal of the Human Biology Council}, volume = {23}, number = {3}, pages = {392-397}, doi = {10.1002/ajhb.21156}, pmid = {21387460}, issn = {1520-6300}, mesh = {Adult ; Age Distribution ; Aged ; Aged, 80 and over ; Female ; History, 20th Century ; Humans ; Hyperostosis Frontalis Interna/*epidemiology/*etiology/history/pathology ; Israel/epidemiology ; *Life Style ; Middle Aged ; Prevalence ; Severity of Illness Index ; Skull/*pathology ; Tomography, X-Ray Computed/methods ; United States/epidemiology ; Young Adult ; }, abstract = {OBJECTIVES: To examine whether the prevalence and severity of hyperostosis frontalis interna (HFI) has significantly changed during the past 100 years.

METHODS: Two female populations, 100 years apart, were studied; 992 historic and 568 present day females. Detection of HFI was carried out via direct observation or CT images (Brilliance 64, Philips Medical Systems, Cleveland, Ohio). HFI was graded according to Hershkovitz et al.’s (1999) 4-scale definition and according May et al.’s (2010c) 3-scale definition.

RESULTS: Following correction for age, present day females manifested a significantly higher HFI prevalence compared with historic females (P < 0.05). The risk of developing HFI was found to be approximately 2.5 times greater in present day females compared with females living 100 years ago (P < 0.05). In the young age cohort, present day females manifested a significantly higher prevalence of HFI type B (P < 0.05), whereas in the old age cohort, a significant difference in the prevalence of HFI types C and D was noted between the two groups (P < 0.05). HFI tended to appear at a younger age in the present population. The last two decades has witnessed an increase in HFI prevalence(from 55.6% to 75%).

CONCLUSIONS: HFI prevalence has increased during the last century, especially among young individuals, possibly indicating a profound change in human fertility patterns, together with the introduction of various hormonal treatments) and new dietary habits.}, } @article {pmid21381850, year = {2011}, author = {Reis, HT and Maniaci, MR and Caprariello, PA and Eastwick, PW and Finkel, EJ}, title = {Familiarity does indeed promote attraction in live interaction.}, journal = {Journal of personality and social psychology}, volume = {101}, number = {3}, pages = {557-570}, doi = {10.1037/a0022885}, pmid = {21381850}, issn = {1939-1315}, mesh = {*Disclosure ; Female ; Humans ; *Interpersonal Relations ; Male ; *Social Desirability ; }, abstract = {Does familiarity promote attraction? Prior research has generally suggested that it does, but a recent set of studies by Norton, Frost, and Ariely (2007) challenged that assumption. Instead, they found that more information about another person, when that information was randomly selected from lists of trait adjectives, using a trait evaluation paradigm, promoted perceptions of dissimilarity and, hence, disliking. The present research began with the assumption that natural social interaction involves contexts and processes not present in Norton et al.'s research or in the typical familiarity experiment. We theorized that these processes imply a favorable impact of familiarity on attraction. Two experiments are reported using a live interaction paradigm in which two previously unacquainted same-sex persons interacted with each other for varying amounts of time. Findings strongly supported the "familiarity leads to attraction" hypothesis: The more participants interacted, the more attracted they were to each other. Mediation analyses identified three processes that contribute to this effect: perceived responsiveness, increased comfort and satisfaction during interaction, and perceived knowledge.}, } @article {pmid21376894, year = {2011}, author = {Sullivan, KA and Smith, SS and Horswill, MS and Lurie-Beck, JK}, title = {Older adults' safety perceptions of driving situations: towards a new driving self-regulation scale.}, journal = {Accident; analysis and prevention}, volume = {43}, number = {3}, pages = {1003-1009}, doi = {10.1016/j.aap.2010.11.031}, pmid = {21376894}, issn = {1879-2057}, mesh = {Accidents, Traffic/prevention & control/psychology ; Aged ; Aging/*psychology ; *Attitude ; Automobile Driving/education/*psychology ; Avoidance Learning ; Dangerous Behavior ; Environment Design ; Female ; Habits ; Humans ; Male ; *Safety ; Self-Assessment ; Socioeconomic Factors ; *Surveys and Questionnaires ; }, abstract = {The term 'driving self-restriction' is used in the road safety literature to describe the behaviour of some older drivers. It includes the notion that older drivers will avoid driving in specific, usually self-identified situations, such as those in which safety is compromised. We sought to identify the situations that older drivers report avoiding; and, to determine the adequacy of a key measure of such behaviour. A sample of 75 drivers aged 65 years and older completed Baldock et al.'s modification of the Driving Habits Questionnaire avoidance items (Baldock et al., 2006), the Driving Behaviour Questionnaire, and open-ended items that elicited written descriptions of the most and least safe driving situation. Consistent with previous results, we found a relatively low level of driving self-restriction and infrequent episodes of aggressive violations. However, when combined with the situation descriptions, these data suggest that Driving Habits Questionnaire did not cover all of the situations that older drivers might choose avoid. We suggest that a new avoidance scale is needed and we present a new item pool that may be used for this purpose.}, } @article {pmid21369423, year = {2010}, author = {Bak, TH}, title = {Motor neuron disease and frontotemporal dementia: One, two, or three diseases?.}, journal = {Annals of Indian Academy of Neurology}, volume = {13}, number = {Suppl 2}, pages = {S81-8}, pmid = {21369423}, issn = {1998-3549}, abstract = {The relationship between motor neurone disease (MND) and frontotemporal dementia (FTD) has been a topic of scientific exploration for over hundred years. A connection between both diseases was first postulated in 1932 and has been strengthened by a steady stream of case reports since then. By the late 20th century, the link between both diseases was firmly established, with the resulting condition often referred to as MND/FTD. Several strands of evidence support the notion of an MND/FTD overlap. First, a small but well-documented group of patients present with a full-blown FTD, associated with MND. Second, subtle but characteristic changes in frontal-executive functions and social cognition have been described in non-demented MND patients, often in association with frontal atrophy/hypoactivity on neuroimaging. Third, amyotrophic features have been documented in patients primarily diagnosed with FTD. Moreover, the same genetic defect can lead to FTD and MND phenotypes in different members of the same family. However, as the current research is moving toward a more fine-grained evaluation, an increasingly complex picture begins to emerge. Some features, such as psychotic symptoms or severe language deficits (particularly in comprehension and verb processing), seem to occur more often in MND/dementia than in the classical FTD. On the basis of the review of 100 years of literature as well as 10 years of clinical experience of longitudinal follow-up of MND/dementia patients, this review argues in favor of MND/dementia (or, more precisely, MND/dementia/aphasia) as a separate clinical entity, not sufficiently explained by a combination of MND and FTD.}, } @article {pmid21360017, year = {2012}, author = {Debiao, H and Jianhua, C and Rui, Z}, title = {A more secure authentication scheme for telecare medicine information systems.}, journal = {Journal of medical systems}, volume = {36}, number = {3}, pages = {1989-1995}, pmid = {21360017}, issn = {0148-5598}, mesh = {*Access to Information ; *Computer Security ; Software Design ; *Telemedicine ; }, abstract = {It is important to guarantee the privacy and the security of the users in the telecare medicine information system. Recently, Wu et al.'s proposed an authentication scheme for mobile devices in telecare medicine information system. They added the pre-computing idea within the communication process to avoid the time-consuming exponential computations. They also claimed their scheme can withstand various attacks. We will show that their scheme suffers from the impersonation attack to the insider's attack. In order to overcome the weaknesses, we propose an improved scheme to eliminate the weakness. Our scheme is not only more secure than Wu et al.'s scheme, but also has better performance. Then our scheme is more efficient and appropriate to collocating with low power mobile devices for the telecare medicine information system.}, } @article {pmid21356100, year = {2011}, author = {Morris, CA and Mervis, CB and Osborne, LR}, title = {Frequency of the 7q11.23 inversion polymorphism in transmitting parents of children with Williams syndrome and in the general population does not differ between North America and Europe.}, journal = {Molecular cytogenetics}, volume = {4}, number = {}, pages = {7}, pmid = {21356100}, issn = {1755-8166}, abstract = {Inversion of the Williams syndrome (WS) region on chromosome 7q11.23 has previously been shown to occur at a higher frequency in the transmitting parents of children with WS than in the general population, suggesting that it predisposes to the WS deletion. Frohnauer et al. recently reported that the frequency of this inversion is not elevated in the parents of children with WS in Germany relative to the German general population. We have compared Frohnauer et al.'s data to those from three previously published studies (Hobart et al., Bayes et al., Osborne et al.), all of which reported a significantly higher rate of 7q11.23 inversion in transmitting parents than in the general population. Results indicated that Frohnauer et al.'s data are consistent with previously reported frequencies of 7q11.23 inversion in North America and Spain in both transmitting parents and the general population.}, } @article {pmid21347971, year = {2011}, author = {Bertamini, M and Bennett, KM and Bode, C}, title = {The anterior bias in visual art: the case of images of animals.}, journal = {Laterality}, volume = {16}, number = {6}, pages = {673-689}, doi = {10.1080/1357650X.2010.508219}, pmid = {21347971}, issn = {1464-0678}, mesh = {Animals ; Art/*history ; *Bias ; Functional Laterality/*physiology ; History, 18th Century ; History, 19th Century ; History, Medieval ; Humans ; Paintings/*history/*psychology ; Visual Perception/*physiology ; }, abstract = {Composition is an important topic in visual art. The literature suggests a bias for objects on the right side (Levy, 1976) and two additional biases with respect to positioning of objects within a rectangular frame: a Centre bias and an Inward bias (Palmer, Gardner, & Wickens, 2008). We analysed images of animals from three datasets of works of art: two datasets were from artists well known for their portraits of animals (Bewick, Stubbs) and the third was a medieval bestiary. There was no overall displacement of the subject to the right or to the left of the picture. However, we found a bias consisting of more space in front compared to behind the animal, consistent with Palmer at al.'s findings and with their definition of an Inward bias. Because our animals never face towards the centre we use the term Anterior bias. In addition, we found a modulation of this bias on the basis of the facing direction of the animal, consisting of a stronger Anterior bias for left-facing animals. This asymmetry may originate from a combination of an Anterior bias and a Right bias. Finally, with respect to size we found that the size of the animals predicted the proportion of the picture occupied, an effect known as "canonical size".}, } @article {pmid21347411, year = {2011}, author = {Rodda, GH and Jarnevich, CS and Reed, RN}, title = {Challenges in identifying sites climatically matched to the native ranges of animal invaders.}, journal = {PloS one}, volume = {6}, number = {2}, pages = {e14670}, pmid = {21347411}, issn = {1932-6203}, mesh = {Animals ; Boidae/physiology ; *Climate ; *Ecosystem ; Internationality ; Introduced Species/*statistics & numerical data ; *Models, Theoretical ; }, abstract = {BACKGROUND: Species distribution models are often used to characterize a species' native range climate, so as to identify sites elsewhere in the world that may be climatically similar and therefore at risk of invasion by the species. This endeavor provoked intense public controversy over recent attempts to model areas at risk of invasion by the Indian Python (Python molurus). We evaluated a number of MaxEnt models on this species to assess MaxEnt's utility for vertebrate climate matching.

Overall, we found MaxEnt models to be very sensitive to modeling choices and selection of input localities and background regions. As used, MaxEnt invoked minimal protections against data dredging, multi-collinearity of explanatory axes, and overfitting. As used, MaxEnt endeavored to identify a single ideal climate, whereas different climatic considerations may determine range boundaries in different parts of the native range. MaxEnt was extremely sensitive to both the choice of background locations for the python, and to selection of presence points: inclusion of just four erroneous localities was responsible for Pyron et al.'s conclusion that no additional portions of the U.S. mainland were at risk of python invasion. When used with default settings, MaxEnt overfit the realized climate space, identifying models with about 60 parameters, about five times the number of parameters justifiable when optimized on the basis of Akaike's Information Criterion.

CONCLUSIONS/SIGNIFICANCE: When used with default settings, MaxEnt may not be an appropriate vehicle for identifying all sites at risk of colonization. Model instability and dearth of protections against overfitting, multi-collinearity, and data dredging may combine with a failure to distinguish fundamental from realized climate envelopes to produce models of limited utility. A priori identification of biologically realistic model structure, combined with computational protections against these statistical problems, may produce more robust models of invasion risk.}, } @article {pmid21323147, year = {2010}, author = {Morton, JB}, title = {Language, bilingualism, and executive functioning in early development.}, journal = {Psychological reports}, volume = {107}, number = {3}, pages = {888-890}, doi = {10.2466/04.11.28.PR0.107.6.888-890}, pmid = {21323147}, issn = {0033-2941}, mesh = {Child ; *Child Development ; *Critical Period, Psychological ; *Executive Function ; Humans ; *Multilingualism ; }, abstract = {Okanda, et al. (2010) reported new evidence concerning associations between language ability, bilingualism, and executive functioning early in development. The paper adds to a growing body of literature suggesting that bilingualism is associated with advantages in executive functioning generally, and the Dimensional Change Card Sort task in particular. However, as with all findings that hinge on between-group comparisons, there is a need to exercise caution before drawing firm conclusions about the effects of bilingualism on the development of executive control. Several lines of recent evidence are outlined that challenge key assumptions underlying the standard account of the bilingual advantage. Okanda, et al.'s findings are discussed in light of this evidence.}, } @article {pmid21311936, year = {2011}, author = {van Tongeren, SP and Degener, JE and Harmsen, HJ}, title = {Comparison of three rapid and easy bacterial DNA extraction methods for use with quantitative real-time PCR.}, journal = {European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology}, volume = {30}, number = {9}, pages = {1053-1061}, pmid = {21311936}, issn = {1435-4373}, mesh = {Bacteriological Techniques/methods ; DNA, Bacterial/*isolation & purification ; Environmental Microbiology ; Escherichia coli/genetics/isolation & purification ; Humans ; Molecular Diagnostic Techniques/methods ; Real-Time Polymerase Chain Reaction/*methods ; Specimen Handling/*methods ; Staphylococcus aureus/genetics/isolation & purification ; }, abstract = {The development of fast and easy on-site molecular detection and quantification methods for hazardous microbes on solid surfaces is desirable for several applications where specialised laboratory facilities are absent. The quantification of bacterial contamination necessitates the assessment of the efficiency of the used methodology as a whole, including the preceding steps of sampling and sample processing. We used quantitative real-time polymerase chain reaction (qrtPCR) for Escherichia coli and Staphylococcus aureus to measure the recovery of DNA from defined numbers of bacterial cells that were subjected to three different DNA extraction methods: the QIAamp DNA Mini Kit, Reischl et al.'s method and FTA Elute. FTA Elute significantly showed the highest median DNA extraction efficiency of 76.9% for E. coli and 108.9% for S. aureus. The Reischl et al. method and QIAamp DNA Mini Kit inhibited the E. coli qrtPCR assay with a 10-fold decrease of detectable DNA. None of the methods inhibited the S. aureus qrtPCR assay. The FTA Elute applicability was demonstrated with swab samples taken from the International Space Station (ISS) interior. Overall, the FTA Elute method was found to be the most suitable to selected criteria in terms of rapidity, easiness of use, DNA extraction efficiency, toxicity, and transport and storage conditions.}, } @article {pmid21299323, year = {2011}, author = {Mädebach, A and Oppermann, F and Hantsch, A and Curda, C and Jescheniak, JD}, title = {Is there semantic interference in delayed naming?.}, journal = {Journal of experimental psychology. Learning, memory, and cognition}, volume = {37}, number = {2}, pages = {522-538}, doi = {10.1037/a0021970}, pmid = {21299323}, issn = {1939-1285}, mesh = {Adolescent ; Adult ; Analysis of Variance ; Attention/*physiology ; *Conflict, Psychological ; Female ; Humans ; Male ; Middle Aged ; Names ; Neuropsychological Tests ; *Pattern Recognition, Visual ; Photic Stimulation ; Reaction Time/*physiology ; Reading ; *Semantics ; Vocabulary ; Young Adult ; }, abstract = {The semantic interference effect in the picture-word interference task is interpreted as an index of lexical competition in prominent speech production models. Janssen, Schirm, Mahon, and Caramazza (2008) challenged this interpretation on the basis of experiments with a novel version of this task, which introduced a task-switching component. Participants either named the picture or read the word, depending on the word's color. Janssen et al. reported semantic interference in picture naming, regardless of whether the word appeared simultaneously with the picture (immediate naming) or 1,000 ms after the picture (delayed naming). Because picture name retrieval is completed in less than 1,000 ms, the finding in delayed naming was taken as evidence against the lexical competition account. In 3 sets of experiments conducted in German and English, we tested for semantic effects in Janssen et al.'s task-switching version and in the standard picture-word interference task. Using identical materials, we obtained sizeable interference effects in the standard task (Experiments 2, 4, and 6) but no effects in the task-switching version (Experiments 1, 3, and 5). When the word reading trials of the task-switching version were replaced with no-go trials (Experiment 7), semantic interference reemerged in immediate naming but was still absent in delayed naming. The experiments question the reliability of Janssen et al.'s critical finding and suggest that theoretical inferences about the origin of semantic effects in the standard picture-word interference task based on results from the task-switching version used by Janssen et al. are difficult to draw.}, } @article {pmid21296095, year = {2011}, author = {Birkner, M and Blath, J and Steinrücken, M}, title = {Importance sampling for Lambda-coalescents in the infinitely many sites model.}, journal = {Theoretical population biology}, volume = {79}, number = {4}, pages = {155-173}, pmid = {21296095}, issn = {1096-0325}, support = {R00 GM080099/GM/NIGMS NIH HHS/United States ; R00-GM080099/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; *Evolution, Molecular ; Gene Frequency/*genetics ; Genetics, Population/*methods ; Markov Chains ; Models, Genetic ; Monte Carlo Method ; Mutation/*genetics ; Sampling Studies ; }, abstract = {We present and discuss new importance sampling schemes for the approximate computation of the sample probability of observed genetic types in the infinitely many sites model from population genetics. More specifically, we extend the 'classical framework', where genealogies are assumed to be governed by Kingman's coalescent, to the more general class of Lambda-coalescents and develop further Hobolth et al.'s (2008) idea of deriving importance sampling schemes based on 'compressed genetrees'. The resulting schemes extend earlier work by Griffiths and Tavaré (1994), Stephens and Donnelly (2000), Birkner and Blath (2008) and Hobolth et al. (2008). We conclude with a performance comparison of classical and new schemes for Beta- and Kingman coalescents.}, } @article {pmid21261432, year = {2011}, author = {Japuntich, SJ and Piper, ME and Leventhal, AM and Bolt, DM and Baker, TB}, title = {The effect of five smoking cessation pharmacotherapies on smoking cessation milestones.}, journal = {Journal of consulting and clinical psychology}, volume = {79}, number = {1}, pages = {34-42}, pmid = {21261432}, issn = {1939-2117}, support = {K05 CA139871/CA/NCI NIH HHS/United States ; KL2 RR025012/RR/NCRR NIH HHS/United States ; M01 RR003186/RR/NCRR NIH HHS/United States ; 1KL2RR025012-01/RR/NCRR NIH HHS/United States ; P50 DA019706/DA/NIDA NIH HHS/United States ; UL1 RR025011/RR/NCRR NIH HHS/United States ; K08 DA025041/DA/NIDA NIH HHS/United States ; 1K05CA139871/CA/NCI NIH HHS/United States ; M01 RR03186/RR/NCRR NIH HHS/United States ; K08DA025041/DA/NIDA NIH HHS/United States ; R01 DA026831/DA/NIDA NIH HHS/United States ; }, mesh = {Bupropion/*therapeutic use ; Dopamine Uptake Inhibitors/*therapeutic use ; Drug Therapy, Combination ; Female ; Humans ; Male ; Nicotine/administration & dosage/*therapeutic use ; Nicotinic Agonists/*therapeutic use ; Recurrence ; Smoking/*drug therapy ; Smoking Cessation/*methods/psychology ; Treatment Outcome ; }, abstract = {OBJECTIVE: Most smoking cessation studies have used long-term abstinence as their primary outcome measure. Recent research has suggested that long-term abstinence may be an insensitive index of important smoking cessation mechanisms. The goal of the current study was to examine the effects of 5 smoking cessation pharmacotherapies using Shiffman et al.'s (2006) approach of examining the effect of smoking cessation medications on 3 process markers of cessation or smoking cessation milestones: initial abstinence, lapse, and the lapse-relapse transition.

METHOD: The current study (N = 1,504; 58.2% female and 41.8% male; 83.9% Caucasian, 13.6% African American, 2.5% other races) examined the effect of 5 smoking cessation pharmacotherapy treatments versus placebo (bupropion, nicotine lozenge, nicotine patch, bupropion + lozenge, patch + lozenge) on Shiffman et al.'s smoking cessation milestones over 8 weeks following a quit attempt.

RESULTS: Results show that all 5 medication conditions decreased rates of failure to achieve initial abstinence and most (with the exception of the nicotine lozenge) decreased lapse risk; however, only the nicotine patch and bupropion + lozenge conditions affected the lapse-relapse transition.

CONCLUSIONS: These findings demonstrate that medications are effective at aiding initial abstinence and decreasing lapse risk but that they generally do not decrease relapse risk following a lapse. The analysis of cessation milestones sheds light on important impediments to long-term smoking abstinence, suggests potential mechanisms of action of smoking cessation pharmacotherapies, and identifies targets for future treatment development.}, } @article {pmid21244192, year = {2011}, author = {Klauer, KC and Kellen, D}, title = {Assessing the belief bias effect with ROCs: reply to Dube, Rotello, and Heit (2010).}, journal = {Psychological review}, volume = {118}, number = {1}, pages = {164-173}, doi = {10.1037/a0020698}, pmid = {21244192}, issn = {1939-1471}, mesh = {*Attitude ; Humans ; *Logic ; Models, Psychological ; *Prejudice ; ROC Curve ; *Signal Detection, Psychological ; }, abstract = {Dube, Rotello, and Heit (2010) argued (a) that the so-called receiver operating characteristic is nonlinear for data on belief bias in syllogistic reasoning; (b) that their data are inconsistent with Klauer, Musch, and Naumer's (see record 2000-02818-008) model of belief bias; (c) that their data are inconsistent with any of the existing accounts of belief bias and only consistent with a theory provided by signal detection theory; and (d) that in fact, belief bias is a response bias effect. In this reply, we present reanalyses of Dube et al.'s data and of old data suggesting (a) that the receiver operating characteristic is linear for binary "valid" versus "invalid" responses, as employed by the bulk of research in this field; (b) that Klauer et al.'s model describes the old data significantly better than does Dube et al.'s model and that it describes Dube et al.'s data somewhat better than does Dube et al.'s model; (c) that Dube et al.'s data are consistent with the account of belief bias by misinterpreted necessity, whereas Dube et al.'s signal detection model does not fit their data; and (d) that belief bias is more than a response bias effect.}, } @article {pmid21244164, year = {2011}, author = {Kim, SY and Wang, Y and Deng, S and Alvarez, R and Li, J}, title = {Accent, perpetual foreigner stereotype, and perceived discrimination as indirect links between English proficiency and depressive symptoms in Chinese American adolescents.}, journal = {Developmental psychology}, volume = {47}, number = {1}, pages = {289-301}, pmid = {21244164}, issn = {1939-0599}, support = {R03 HD051629/HD/NICHD NIH HHS/United States ; R24 HD042849/HD/NICHD NIH HHS/United States ; R24HD042849-08/HD/NICHD NIH HHS/United States ; R03HD051629-02/HD/NICHD NIH HHS/United States ; }, mesh = {Adolescent ; Age Factors ; Asian/ethnology/*psychology ; California/epidemiology ; Child ; Depression/epidemiology/ethnology/*psychology ; *Discrimination, Psychological ; Emigrants and Immigrants/psychology ; Female ; Humans ; *Language ; Male ; Risk Factors ; Sex Factors ; *Stereotyping ; Students/*psychology ; Surveys and Questionnaires ; }, abstract = {The current study uses García Coll et al.'s (1996) developmental competence model of ethnic minority children and Kim's (1999) racial triangulation theory as frameworks for investigating the mechanisms whereby early adolescent English proficiency relates to perceived discriminatory experiences and adolescent depressive symptoms. Data from 444 adolescents (239 girls and 205 boys, with a mean age of 13.0 years for Wave 1 and 17.0 years for Wave 2) and their parents living in major metropolitan areas of Northern California were collected. The structural equation modeling analyses indicate that self-reported low levels of English proficiency among Chinese American adolescents in middle school are related to these same students later reporting that they speak English with an accent in high school, which in turn relates significantly to their perceiving that they have been stereotyped as perpetual foreigners. For girls, a perpetual foreigner stereotype relates to perceptions of chronic daily discrimination, increasing the risk of depressive symptoms. For boys, the path is different: A perpetual foreigner stereotype is apparently related to discriminatory victimization experiences, which increase the risk of depressive symptoms.}, } @article {pmid21243604, year = {2010}, author = {Schauenburg, H and Leiendecker, C and Simon, R and Küchenhoff, J and Franz, M}, title = {[Work in progress--why evidence-based guidelines do not mean the end of controversial discussions].}, journal = {Zeitschrift fur Psychosomatische Medizin und Psychotherapie}, volume = {56}, number = {4}, pages = {343-347}, doi = {10.13109/zptm.2010.56.4.343}, pmid = {21243604}, issn = {1438-3608}, mesh = {Antidepressive Agents/*therapeutic use ; Combined Modality Therapy ; Consensus ; Depressive Disorder/*therapy ; *Evidence-Based Medicine ; Germany ; Humans ; *Practice Guidelines as Topic ; *Psychotherapy ; Randomized Controlled Trials as Topic ; }, abstract = {Härter et al.s (2010) statement points to differences in the interpretation of the German National Guidelines for the treatment of depression and adds some of the recommendations missing in the original paper. The response again stresses the general consensus and relates to controversies that did not find entry into the recommendations, although they are important for establishing a transparency in the discussion process. Not all clinically relevant questions can be answered based on evidence (e.g. differential indication as to treatment duration). Also, the issue of external validity has to be discussed again and again to ensure reception and implementation of clinical guidelines. Finally, the very cooperative process of the guideline development is pointed out.}, } @article {pmid21218290, year = {2011}, author = {Walker, MP}, title = {In sleep lost, emotions become unrecognized: Commentary on Minkel et al.'s, "Emotional expressiveness in sleep-deprived healthy adults".}, journal = {Behavioral sleep medicine}, volume = {9}, number = {1}, pages = {15-17}, doi = {10.1080/15402002.2011.533990}, pmid = {21218290}, issn = {1540-2010}, mesh = {Adult ; *Emotions ; *Facial Expression ; Female ; Humans ; Male ; Middle Aged ; Motion Pictures ; Neuropsychological Tests ; Sleep Deprivation/*psychology ; }, } @article {pmid21199498, year = {2011}, author = {Flouri, E and Panourgia, C}, title = {Gender differences in the pathway from adverse life events to adolescent emotional and behavioural problems via negative cognitive errors.}, journal = {The British journal of developmental psychology}, volume = {29}, number = {Pt 2}, pages = {234-252}, doi = {10.1348/0261-510X.002002}, pmid = {21199498}, issn = {0261-510X}, mesh = {Adolescent ; Affective Symptoms/*psychology ; Attention ; Catastrophization/diagnosis/psychology ; Child ; Child Behavior Disorders/*psychology ; Cognition Disorders/*psychology ; Conduct Disorder/diagnosis/psychology ; *Defense Mechanisms ; Female ; *Gender Identity ; Generalization, Psychological ; Humans ; Hyperkinesis/diagnosis/psychology ; Internal-External Control ; *Life Change Events ; Male ; Peer Group ; Personality Inventory/statistics & numerical data ; Psychometrics ; Social Adjustment ; }, abstract = {The aim of this study was to test for gender differences in how negative cognitive errors (overgeneralizing, catastrophizing, selective abstraction, and personalizing) mediate the association between adverse life events and adolescents' emotional and behavioural problems (measured with the Strengths and Difficulties Questionnaire). The sample consisted of 202 boys and 227 girls (aged 11-15 years) from three state secondary schools in disadvantaged areas in one county in the South East of England. Control variables were age, ethnicity, special educational needs, exclusion history, family structure, family socio-economic disadvantage, and verbal cognitive ability. Adverse life events were measured with Tiet et al.'s (1998) Adverse Life Events Scale. For both genders, we assumed a pathway from adverse life events to emotional and behavioural problems via cognitive errors. We found no gender differences in life adversity, cognitive errors, total difficulties, peer problems, or hyperactivity. In both boys and girls, even after adjustment for controls, cognitive errors were related to total difficulties and emotional symptoms, and life adversity was related to total difficulties and conduct problems. The life adversity/conduct problems association was not explained by negative cognitive errors in either gender. However, we found gender differences in how adversity and cognitive errors produced hyperactivity and internalizing problems. In particular, life adversity was not related, after adjustment for controls, to hyperactivity in girls and to peer problems and emotional symptoms in boys. Cognitive errors fully mediated the effect of life adversity on hyperactivity in boys and on peer and emotional problems in girls.}, } @article {pmid21161763, year = {2010}, author = {Aveling, EL}, title = {The impact of aid chains: relations of dependence or supportive partnerships for community-led responses to HIV/AIDS?.}, journal = {AIDS care}, volume = {22 Suppl 2}, number = {}, pages = {1588-1597}, doi = {10.1080/09540121.2010.507954}, pmid = {21161763}, issn = {1360-0451}, mesh = {Cambodia ; Community Networks/*organization & administration ; Delivery of Health Care/organization & administration ; HIV Infections/*therapy ; Humans ; Interinstitutional Relations ; International Cooperation ; Voluntary Health Agencies/organization & administration ; }, abstract = {In the context of increasing global emphasis on partnerships between international, governmental and civil society organisations in the distribution of international aid, this paper examines the ways in which the resulting aid chains promote and undermine community-led responses to HIV/AIDS. The impact of the aid-granting system is examined using an ethnographic case study of an HIV/AIDS prevention programme with Cambodian military families. The case study draws on observations of stakeholder meetings and programme activities, interviews with stakeholders (the donor, NGOs and military community) and textual materials (programme guidelines, policies and reports). Campbell et al.'s interrelated concepts of relational, symbolic and material context are used to frame the analysis. The establishment of a relationship with a more powerful international NGO is shown to be beneficial to the military community and civil society groups. The international NGO uses its significant material and economic leverage to improve the community's relational context (by ensuring the support of the military high command), symbolic context (by strengthening the position of community and civil society partners in relation to government bodies) and material context (through increasing access to health services). However, material and symbolic asymmetries between partners in the aid chain persist, curtailing the community's involvement and leadership. At the material and relational levels, the hierarchical flow of aid encourages accountability to the demands of the donor while excluding grassroots groups from directly accessing funding. At the symbolic level, problem-focused representations of the military further reinforce the community's position as recipients of intervention, which undermines recognition for the community's knowledge, strengths and right to fully participate. Thus while aid chains can be supportive of community-led responses, this analysis highlights how the structures and dynamics of international aid continue to position marginalised communities as recipients, not leaders, of HIV/AIDS programmes, raising particular dilemmas for intermediary international NGOs.}, } @article {pmid21184159, year = {2011}, author = {Spector, JE}, title = {Sight word instruction for students with autism: an evaluation of the evidence base.}, journal = {Journal of autism and developmental disorders}, volume = {41}, number = {10}, pages = {1411-1422}, pmid = {21184159}, issn = {1573-3432}, mesh = {Adolescent ; Autistic Disorder/*psychology ; Child ; Child, Preschool ; Evidence-Based Practice ; Humans ; Learning ; Male ; *Reading ; Retention, Psychology ; *Students ; Teaching/*methods ; }, abstract = {This paper reviews the evidence on sight word instruction as a method of teaching students with autism and significant cognitive and verbal limitations to read printed words. Nine single-subject studies were rated using Reichow et al.'s (J Autism Dev Disord 38:1311-1319, 2008) evaluative method for identifying evidence-based practice, and studies with at least adequate methodology were analyzed to identify common intervention features. Results yielded evidence in support of a massed trials approach featuring student response to a succession of items, differential positive reinforcement, systematic prompting, and use of visual supports. Across studies, students learned to identify printed words, even those with limited oral language and no prior reading instruction. However, no studies addressed the effects of sight word instruction on broad literacy outcomes.}, } @article {pmid21171785, year = {2011}, author = {Engdahl, RM and Elhai, JD and Richardson, JD and Frueh, BC}, title = {Comparing posttraumatic stress disorder's symptom structure between deployed and nondeployed veterans.}, journal = {Psychological assessment}, volume = {23}, number = {1}, pages = {1-6}, doi = {10.1037/a0020045}, pmid = {21171785}, issn = {1939-134X}, mesh = {Adult ; Aged ; Canada ; Checklist ; Factor Analysis, Statistical ; Female ; Humans ; Male ; Middle Aged ; Models, Psychological ; Stress Disorders, Post-Traumatic/diagnosis/*psychology ; Surveys and Questionnaires ; Veterans/*psychology ; Warfare ; Young Adult ; }, abstract = {We tested two empirically validated 4-factor models of posttraumatic stress disorder (PTSD) symptoms using the PTSD Checklist: King, Leskin, King, and Weathers' (1998) model including reexperiencing, avoidance, emotional numbing, and hyperarousal factors, and Simms, Watson, and Doebbeling's (2002) model including reexperiencing, avoidance, dysphoria, and hyperarousal. Our aim was to determine which fit better in two groups of military veterans: peacekeepers previously deployed to a war zone (deployed group) and those trained for peacekeeping operations who were not deployed (nondeployed group). We compared the groups using multigroup confirmatory factor analysis. Adequate model fit was demonstrated among the nondeployed group, with no significant difference between King et al.'s (1998) model (separating avoidance and numbing) and Simms et al.'s (2002) similar model involving a dysphoria factor. A better fitting factor structure consistent with Simms et al.'s (2002) model was found in the deployed group. Comprehensive measurement invariance testing demonstrated significant differences between the deployed and nondeployed groups on all structural parameters, except observed variable intercepts (thus indicating similarities only in PTSD item severity). These findings add to researchers' understanding of PTSD's factor structure, given the revision of PTSD that will appear in the forthcoming 5th edition of the Diagnostic and Statistical Manual of Mental Disorders (American Psychiatric Association, 2010)--namely, that the factor structure may be quite different between groups with and without exposure to major traumatic events.}, } @article {pmid21171741, year = {2011}, author = {Worthington, RL and Dillon, FR}, title = {Deconstructing multicultural counseling competencies research: comment on Owen, Leach, Wampold, and Rodolfa (2011).}, journal = {Journal of counseling psychology}, volume = {58}, number = {1}, pages = {10-5; discussion 22-6}, doi = {10.1037/a0022177}, pmid = {21171741}, issn = {0022-0167}, mesh = {*Counseling ; *Cultural Competency ; Ethnicity/*psychology ; Guideline Adherence ; Humans ; Models, Psychological ; Outcome Assessment, Health Care ; *Patient Satisfaction ; Professional Competence ; }, abstract = {The present article offers a commentary and critique of the research presented by J. Owen, M. M. Leach, B. Wampold and E. Rodolfa (2011). Given the complexity of the research methodology, findings, and conclusions, the authors provide a concise summary of findings, study limitations, and conclusions followed by a detailed critique of the study. The authors respect and appreciate the ambitious efforts made by Owen et al. to address gaps in the literature regarding outcome research using client ratings of counselors' multicultural counseling competencies (MCCs). The authors provide a critical analysis of some of J. Owen et al.'s specific conclusions and offer alternative conclusions based on conceptual and methodological bases. The authors use the opportunity to comment on this study as a means of advancing recommendations regarding future research on MCCs that might contribute to substantive revisions to the long-standing theoretical foundation in this area.}, } @article {pmid21152074, year = {2010}, author = {Zhang, M and Gilbert, PB}, title = {Increasing the Efficiency of Prevention Trials by Incorporating Baseline Covariates.}, journal = {Statistical communications in infectious diseases}, volume = {2}, number = {1}, pages = {}, pmid = {21152074}, issn = {2194-6310}, support = {R01 AI054165/AI/NIAID NIH HHS/United States ; R37 AI054165/AI/NIAID NIH HHS/United States ; }, abstract = {Most randomized efficacy trials of interventions to prevent HIV or other infectious diseases have assessed intervention efficacy by a method that either does not incorporate baseline covariates, or that incorporates them in a non-robust or inefficient way. Yet, it has long been known that randomized treatment effects can be assessed with greater efficiency by incorporating baseline covariates that predict the response variable. Tsiatis et al. (2007) and Zhang et al. (2008) advocated a semiparametric efficient approach, based on the theory of Robins et al. (1994), for consistently estimating randomized treatment effects that optimally incorporates predictive baseline covariates, without any parametric assumptions. They stressed the objectivity of the approach, which is achieved by separating the modeling of baseline predictors from the estimation of the treatment effect. While their work adequately justifies implementation of the method for large Phase 3 trials (because its optimality is in terms of asymptotic properties), its performance for intermediate-sized screening Phase 2b efficacy trials, which are increasing in frequency, is unknown. Furthermore, the past work did not consider a right-censored time-to-event endpoint, which is the usual primary endpoint for a prevention trial. For Phase 2b HIV vaccine efficacy trials, we study finite-sample performance of Zhang et al.'s (2008) method for a dichotomous endpoint, and develop and study an adaptation of this method to a discrete right-censored time-to-event endpoint. We show that, given the predictive capacity of baseline covariates collected in real HIV prevention trials, the methods achieve 5-15% gains in efficiency compared to methods in current use. We apply the methods to the first HIV vaccine efficacy trial. This work supports implementation of the discrete failure time method for prevention trials.}, } @article {pmid21146425, year = {2011}, author = {Horton, CL}, title = {A commentary on Blagrove et al.'s dream-lag replication: implications for memory sources.}, journal = {Consciousness and cognition}, volume = {20}, number = {2}, pages = {392-393}, doi = {10.1016/j.concog.2010.10.016}, pmid = {21146425}, issn = {1090-2376}, mesh = {Cognition ; Dreams/*physiology/psychology ; Humans ; Memory/*physiology ; Sleep/physiology ; Time Factors ; }, } @article {pmid21144262, year = {2010}, author = {Gyekye, SA and Salminen, S}, title = {Organizational safety climate and work experience.}, journal = {International journal of occupational safety and ergonomics : JOSE}, volume = {16}, number = {4}, pages = {431-443}, doi = {10.1080/10803548.2010.11076856}, pmid = {21144262}, issn = {1080-3548}, mesh = {Accidents, Occupational/statistics & numerical data ; Adolescent ; Adult ; Analysis of Variance ; Chi-Square Distribution ; Female ; Ghana ; Humans ; Industry ; Job Satisfaction ; Male ; Middle Aged ; *Occupational Health ; *Organizational Culture ; *Perception ; }, abstract = {The study examined the relationships between work experience and (a) safety perceptions, (b) job satisfaction, (c) compliance with safety management policies and (d) accident frequency. Participants were Ghanaian industrial workers (N = 320). They were divided into 2 cohorts: experienced and inexperienced workers. Workplace safety perceptions were assessed with Hayes et al.'s 50-item work safety scale. MANOVA was used to test for differences of statistical significance. Posterior comparison with t test consistently revealed significant differences between experienced cohorts and their inexperienced counterparts. Experienced workers indicated the best perceptions on safety, expressed the highest level of job satisfaction, were the most compliant with safety procedures and recorded the lowest accident frequency. From a practical perspective, analysing differences in work experience in relation to safety perceptions could be useful for organizations as the workers' experience could indicate a need for special safety programmes for particular groups.}, } @article {pmid21133561, year = {2010}, author = {Owen, J and Wong, YJ and Rodolfa, E}, title = {The relationship between clients' conformity to masculine norms and their perceptions of helpful therapist actions.}, journal = {Journal of counseling psychology}, volume = {57}, number = {1}, pages = {68-78}, doi = {10.1037/a0017870}, pmid = {21133561}, issn = {0022-0167}, mesh = {Adolescent ; Adult ; *Counseling ; Female ; *Gender Identity ; *Helping Behavior ; Humans ; Male ; Mental Health Services ; *Patient Satisfaction ; Personality Inventory/statistics & numerical data ; Psychometrics ; *Psychotherapy ; *Social Conformity ; *Social Values ; Student Health Services ; Treatment Outcome ; Young Adult ; }, abstract = {T. J. G. Tracey et al.'s (2003) common factors model derived from therapists and psychotherapy researchers has provided a parsimonious structure to inform research and practice. Accordingly, the current authors used the 14 common factor categories identified in Tracey et al.'s model as a guide to code clients' perceptions of helpful therapist actions (e.g., intervention, way of being) in short-term psychotherapy. Next, they conducted a cluster analysis to establish meaningful subgroups of clients based on clients' perceptions of helpful therapist actions. Finally, they explored if clients in these subgroups differed in their report of conformity to masculine norms. Clients (N = 161) from a university counseling center were recruited for the current study. Results revealed 3 clusters of clients based on their perceptions of helpful therapist actions: Insight (44%), Relationship (30%), and Information (26%). In contrast, Tracey et al. found 3 clusters: Bond (which includes Insight and Relationship), Information, and Structure of therapy (not found in the current study). Clients in the Insight and Relationship clusters reported more conformity to masculine norms as compared with clients in the Information cluster. There were no sex differences across clusters.}, } @article {pmid21133524, year = {2010}, author = {Winegard, B and Bailey, DH and Oxford, J and Geary, DC}, title = {Trade-offs and individual differences in evolved traits.}, journal = {The American psychologist}, volume = {65}, number = {9}, pages = {928-929}, doi = {10.1037/a0021198}, pmid = {21133524}, issn = {1935-990X}, mesh = {*Biological Evolution ; Humans ; *Individuality ; Psychology ; *Social Behavior ; }, abstract = {Comments on Evolutionary psychology: Controversies, questions, prospects, and limitations (see record 2010-02208-001) by Confer et al. We applaud Confer et al.'s (February-March 2010) clarifications of the many misconceptions surrounding the use of evolutionary analyses in psychology. As they noted, such misunderstandings are common and result in a curious tendency of some of our colleagues to criticize evolutionary psychology without a firm understanding of evolution itself. Confer et al. also did an admirable job acknowledging current unresolved issues among evolutionary psychologists (e.g., the relative importance of group selection on humans). The above said, we disagree with their view that a current limitation of evolutionary psychology is its inability to explain phenomena "that appear to reduce an individual's reproductive success, and cannot be explained by mismatches with, or hijacking of, our psychological mechanisms by modern-day novel inputs" (Confer et al., 2010, p. 122). Mismatches between modern environments and environments of evolutionary adaptedness are only one set of explanations for seemingly maladaptive traits (Nesse, 2005). Another set involves evolutionary trade-offs.}, } @article {pmid21130234, year = {2010}, author = {Corrion, K and Scoffier, S and Gernigon, C and Cury, F and d'Arripe-Longueville, F}, title = {[Development and factorial validity of a moral disengagement in Sport Short Scale].}, journal = {L'Encephale}, volume = {36}, number = {6}, pages = {495-503}, doi = {10.1016/j.encep.2010.03.003}, pmid = {21130234}, issn = {0013-7006}, mesh = {Adolescent ; Aggression/psychology ; Athletes/*psychology ; *Cross-Cultural Comparison ; Deception ; Factor Analysis, Statistical ; Female ; France ; Harm Reduction ; Humans ; Male ; Mathematical Computing ; *Moral Obligations ; Personality Inventory/*statistics & numerical data ; Psychometrics/statistics & numerical data ; Reproducibility of Results ; Translating ; Young Adult ; }, abstract = {BACKGROUND: According to Bandura, individuals are able to violate their personal standards, without self-sanction, by using the psychological operations of moral disengagement. For Bandura et al., moral disengagement is characterized by eight mechanisms belonging to one of the following four groups: (a) reconstructing conduct; (b) reconsideration of negative effects; (c) disqualification of the victim; and (d) obscuring of personal causal agency. Other researchers have measured moral disengagement in various contexts of everyday life using Bandura et al.'s scale and suggested that moral disengagement mechanisms would fall into two or three groups according to context. One context in which moral issues have a major role is sport.

METHODS: Three complementary studies were carried out on a total of 1305 young French adult athletes to develop and validate a Short French Questionnaire of Moral Disengagement in Sport (SFQMDS) and to test its invariance according to gender. STUDY 1: With reference to the existing literature, an initial French version of the SFQDMS was developed. French university students (n=220) then voluntarily completed the questionnaire. The validity of this preliminary version and the clarity of the items were examined and ascertained, and factorial analyses identified 10 items that loaded onto two factors (i.e., projecting fault onto others or sharing of responsibility; minimization of transgression and their consequences). Each factor displayed good internal consistency. STUDY 2: Confirmatory factor analysis (CFA) was conducted using AMOS 7.0 software. The sample included 1021 French university students (M(age)=21.52; SD=2.34). The first analysis of the data from 298 French students suggested that four items should be eliminated. The six-item model was then tested with a CFA of the data from 723 other participants (M(age)=21.51; SD=2.34) and exhibited acceptable fit indices: (χ² [8, 723]=1.54; p>0.09; GFI=0.97; TLI=0.97; CFI=0.97; RMSEA=0.03; RMSEA LO/HI=0.01/0.05). These results confirmed the bifactorial structure of the instrument, as well as its partial invariance across genders at the most complex level (i.e., strict) of its factorial structure. These statistical analyses demonstrated the excellent internal consistency and very good construct validity of the SFQDMS. STUDY 3: The third study examined the temporal stability of the SFQDMS and its theoretical validity with a sample of 221 French students (M(age)=21.00; SD=2.05). Our results were found to be stable over time. From a theoretical standpoint, the SFQDMS was related to existing instruments that measure individuals' affective self-regulatory efficacy and prosocial behavior. These results demonstrated the external validity of the instrument.

CONCLUSION: The overall results presented in these studies confirmed the good psychometric properties of the SFQDMS. This questionnaire consists of two subscales of three items measuring two groups of moral disengagement. The first involves projecting the fault for one's own transgressions onto others or sharing of responsibility (e.g., "It's not my fault if I behave badly [cheating or aggression] because it's my opponent who started it"). The second subscale involves the minimization of transgressions and their consequences (e.g., "It's not serious if I behave badly [cheating or aggression] because I do it to keep the advantage"). This instrument is a reliable tool that could be fruitfully used in future research addressing the moral disengagement of French adolescents or adults in sport. A deeper understanding of the processes involved in moral disengagement would facilitate the development of strategies to prevent or remediate transgressive behavior in the sport domain.}, } @article {pmid21117486, year = {2010}, author = {Masip, J and Garrido, E and Herrero, C}, title = {Regression toward the mean or heuristic processing in detecting deception? Reply to Elaad (2010).}, journal = {Psychological reports}, volume = {107}, number = {2}, pages = {587-592}, doi = {10.2466/03.07.PR0.107.5.587-592}, pmid = {21117486}, issn = {0033-2941}, mesh = {Bias ; Humans ; *Judgment ; *Lie Detection ; Personality Assessment/statistics & numerical data ; Psychometrics ; Reference Values ; *Regression Analysis ; *Truth Disclosure ; Videotape Recording ; }, abstract = {Masip, et al. (2009) conducted a study in which observers had to make truth-lie judgments at the beginning, middle, or end of a series of videotaped statements. They found a decline in truth judgments over time and explained this finding in terms of information processing mode. Recently, Elaad (2010) challenged this explanation and contended that the decline could be a result of regression toward the mean. In the present paper, it is argued that because Masip, et al. took multiple Moment 1 judgments over time and then averaged across judgments, regression toward the mean was extremely unlikely. Furthermore, the decrease in truth judgments was found under several separate conditions; this cannot be explained by random fluctuations alone. Finally, Masip, et al.'s data were re-analyzed adjusting for the effects of regression toward the mean. The outcomes of these analyses were the same as those reported in the original article.}, } @article {pmid21116042, year = {2011}, author = {Wang, BF and Lin, CH}, title = {Improved algorithms for finding gene teams and constructing gene team trees.}, journal = {IEEE/ACM transactions on computational biology and bioinformatics}, volume = {8}, number = {5}, pages = {1258-1272}, doi = {10.1109/TCBB.2010.127}, pmid = {21116042}, issn = {1557-9964}, mesh = {*Algorithms ; Animals ; Databases, Genetic ; Genome ; Genomics/*methods ; Humans ; Mice ; *Models, Genetic ; Multigene Family/*genetics ; }, abstract = {A gene team is a set of genes that appear in two or more species, possibly in a different order yet with the distance between adjacent genes in the team for each chromosome always no more than a certain threshold δ. A gene team tree is a succinct way to represent all gene teams for every possible value of δ. In this paper, improved algorithms are presented for the problem of finding the gene teams of two chromosomes and the problem of constructing a gene team tree of two chromosomes. For the problem of finding gene teams, Beal et al. had an O(n lg2 n)-time algorithm. Our improved algorithm requires O(n lg t) time, where t ≤ n is the number of gene teams. For the problem of constructing a gene team tree, Zhang and Leong had an O(n lg2 n)-time algorithm. Our improved algorithm requires O(n lg n lglg n) time. Similar to Beal et al.'s gene team algorithm and Zhang and Leong's gene team tree algorithm, our improved algorithms can be extended to k chromosomes with the time complexities increased only by a factor of k.}, } @article {pmid21113826, year = {2011}, author = {Young, G}, title = {On abductive inference and delusional belief: why there is still a role for patient experience within explanations of Capgras delusion.}, journal = {Cognitive neuropsychiatry}, volume = {16}, number = {4}, pages = {303-325}, doi = {10.1080/13546805.2010.531626}, pmid = {21113826}, issn = {1464-0619}, mesh = {Attitude to Health ; Capgras Syndrome/*psychology ; *Defense Mechanisms ; Delusions/*psychology ; Humans ; *Models, Psychological ; }, abstract = {This paper aims to examine critically the explanatory model of delusional belief presented in Coltheart, Menzies, and Sutton's (2010) paper, "Abductive Inference and Delusional Belief". The authors acknowledge that certain aspects of the model are speculative. In return, I speculate over the likelihood that the model's emphasis on subpersonal processing adequately and coherently explains the symptoms (as best we know them) of patients with delusional misidentification (specifically, the Capgras delusion) and nondeluded equivalent patient groups. In addition, I offer an account of the Capgras delusion that is compatible with many of the tenets of Coltheart et al.'s model, but which preserves an important explanatory role for patient experience absent, and erroneously so, I contend, from the aforementioned model. The more integrated explanation I am proposing here also provides a number of pertinent empirical questions and testable hypotheses that could inform future models of delusional belief.}, } @article {pmid21113275, year = {2010}, author = {Golinelli, D and Ryan, G and Green, HD and Kennedy, DP and Tucker, JS and Wenzel, SL}, title = {Sampling to reduce respondent burden in personal network studies and its effect on estimates of structural measures.}, journal = {Field methods}, volume = {22}, number = {3}, pages = {217-230}, pmid = {21113275}, issn = {1525-822X}, support = {R01 AA015301/AA/NIAAA NIH HHS/United States ; }, abstract = {Recently, researchers have been increasingly interested in collecting personal network data. Collecting this type of data is particularly burdensome on the respondents, who need to elicit the names of alters, answer questions about each alter (network composition), and evaluate the strength of possible relationships among the named alters (network structure). In line with McCarty et al.'s (2007) research, we propose reducing respondent burden by randomly sampling a smaller set of alters from those originally elicited. Via simulation, we assess the estimation error we incur when measures of the network structure are computed on a random sample of alters and illustrate the trade-offs between reduction in respondent burden (measured with the amount of interview time saved) and total estimation error incurred. Researchers can use the provided trade-offs figure to make an informed decision regarding the number of alters to sample when in need to reduce respondent burden.}, } @article {pmid21094320, year = {2011}, author = {Boccara, V and Delhomme, P and Vidal-Gomel, C and Rogalski, J}, title = {Time course of driving-skill self-assessments during French driver training.}, journal = {Accident; analysis and prevention}, volume = {43}, number = {1}, pages = {241-246}, doi = {10.1016/j.aap.2010.08.016}, pmid = {21094320}, issn = {1879-2057}, mesh = {Adolescent ; Adult ; Automobile Driving/*education/*psychology ; Female ; Humans ; Male ; Paris ; Practice, Psychological ; *Self-Assessment ; Sex Factors ; Young Adult ; }, abstract = {Promoting self-assessment accuracy among student drivers could help improve the road safety for young novice drivers (Minimum Requirement for Driving Instructor Training, 2005). However, it is essential to first examine the time course of student drivers' assessments of their own driving skills. As a result, the present study examined the time course of student drivers' self-assessments in relation to their general driving abilities during the four steps of French driver training. We used Victoir et al.'s (2005) self-efficacy scale, which we translated into French. We set four goals for the present study: (1) to examine the psychometric qualities of this self-assessment scale, (2) to study the time courses of the students' self-assessments, (3) to investigate the relationship of these time courses to the number of driving hours that the students estimated that they needed to complete before taking the driving test, and (4) to compare the number of hours estimated by the students to the number of hours estimated by their driving instructors. In total, 150 students (58 men and 92 women) and 38 instructors from 13 driving schools in Paris participated in the present study. The self-assessment scale was composed of 12 items that were rated on a 7-point Likert scale that ranged from 1 (certainly so) to 7 (certainly not). The internal consistency of the scale was satisfactory (α=.88). The self-assessments became increasingly positive as the training progressed (at the beginning of training, M=3.45 vs. at the completion of the training, M=4.8). Globally, the men assessed themselves more positively than the women. However, no significant gender difference was observed at each training step. The students' self-ratings were negatively correlated with the number of driving hours that they estimated they still needed before taking the driving test. This number did not differ significantly from the number of hours that was estimated by the instructors at each training step throughout the training. The results describing the time course of the student drivers' self-assessments during driver training and this time course's correlation with the estimated number of driving hours still needed to take the driver test were discussed.}, } @article {pmid21040036, year = {2010}, author = {Randi, E}, title = {Wolves in the Great Lakes region: a phylogeographic puzzle.}, journal = {Molecular ecology}, volume = {19}, number = {20}, pages = {4386-4388}, doi = {10.1111/j.1365-294X.2010.04819.x}, pmid = {21040036}, issn = {1365-294X}, mesh = {Animals ; Coyotes/classification/*genetics ; Great Lakes Region ; *Hybridization, Genetic ; *Phylogeography ; Wolves/classification/*genetics ; }, abstract = {Empirical studies demonstrate that natural hybridization in animals is more common than thought so far (Mallet 2005), particularly among species that originated recently through cycles of population contraction-expansion arising from climate changes over the last glacial period, the Pleistocene. In addition, the post-glacial global growth of human populations has fostered anthropogenic hybridization events, mediated by habitat changes, the persecution of large predators and the introduction of alien species (Allendorf et al. 2001). The Canis lineage shows cases of both natural and anthropogenic hybridization, exacerbating the controversy about the number of species that should be formally validated in the taxonomic lists, the evolutionary role of genetic introgression and the ways to manage hybrids with invading wild or domesticated populations. The study by Wheeldon et al. (2010), published in this issue of Molecular Ecology, adds a new piece to the intricate puzzle of evolution and taxonomy of Canis in North America. They show that sympatric wolves (C. lupus) and coyotes (C. latrans) are not (extensively) hybridizing in the western North American Great Lakes region (GLR). Widespread hybridization between coyotes and a genetically distinct, but closely related, wolf-like population (the eastern wolf) occurred in the northeastern regions of North America. In Wheeldon et al.'s (2010) opinion, these data should prove definitely that two different species of wolf (the western gray wolf C. lupus and the eastern wolf C. lycaon) and their hybrids are distributed across the GLR.}, } @article {pmid21039097, year = {2010}, author = {Schofield, SJ and Bradley, S and Macrae, C and Nathwani, D and Dent, J}, title = {How we encourage faculty development.}, journal = {Medical teacher}, volume = {32}, number = {11}, pages = {883-886}, doi = {10.3109/0142159X.2010.506564}, pmid = {21039097}, issn = {1466-187X}, mesh = {Education ; Education, Medical, Undergraduate ; *Faculty, Medical ; Humans ; *Motivation ; Organizational Case Studies ; Program Development ; Schools, Medical ; Scotland ; Staff Development/*organization & administration ; Surveys and Questionnaires ; }, abstract = {Most clinicians enjoy teaching medical students, but many have had little training as clinical teachers. The General Medical Council (GMC) in 'Good Medical Practice' states 'if you are involved in teaching you must develop the skills, attitudes and practices of a competent teacher' (GMC 2006). Mclean et al.'s (2008) AMEE guide on faculty development outlines practice points for those responsible for developing their faculty's educational skills. In this article, we look at one health region, Tayside in East Scotland, where the University of Dundee, NHS Education for Scotland (NES) and NHS Tayside are collaborating to implement these practice points. This combined approach has proved to be effective in progressing staff development and recruiting additional clinical colleagues to develop their teaching role.}, } @article {pmid21033548, year = {2010}, author = {Guruge, S and Shirpak, KR and Hyman, I and Zanchetta, M and Gastaldo, D and Sidani, S}, title = {A meta-synthesis of post-migration changes in marital relationships in Canada.}, journal = {Canadian journal of public health = Revue canadienne de sante publique}, volume = {101}, number = {4}, pages = {327-331}, pmid = {21033548}, issn = {0008-4263}, support = {//Canadian Institutes of Health Research/Canada ; }, mesh = {Canada ; *Emigration and Immigration ; Female ; Humans ; Life Change Events ; Male ; *Marital Status ; }, abstract = {OBJECTIVES: Immigration to a new country constitutes a major life change and challenge that can directly and indirectly affect the health of individuals and families. A systematic review was conducted to identify post-migration changes and understand their impact on immigrants' marital relationships in Canada.

METHOD: Using Noblit and Hare's meta-ethnography steps and Paterson et al.'s meta-data method, we conducted a meta-synthesis of qualitative articles.

SYNTHESIS: Four journal articles and one book chapter met the inclusion criteria. Our synthesis of these studies identified three key themes reflecting the major post-migration changes experienced by couples: changes in gender and sexual relations, loss of social networks and support, and de-skilling and de-professionalization. The importance of communication emerged as a fourth theme that cut across the three key themes. These post-migration changes were common across nine ethnic communities, and affected the couple as a unit as well as individuals within this unit, both negatively and positively. The changes were associated with four outcomes: abuse, separation/divorce, staying with each other, and resilience. The synthesis also showed various pathways that link the post-migration changes and their outcomes.

CONCLUSION: Understanding post-migration changes, their outcomes, and the pathways that link them is useful in developing health promotion activities to promote couples' resilience as well as health interventions to reduce the negative impact of the changes on couples and individuals. These activities and interventions must be planned at micro, meso, and macro levels of society.}, } @article {pmid20967077, year = {2010}, author = {Zhang, Y and Chen, W and Wang, S and Yin, ZQ and Xu, FX and Wu, XW and Dong, CH and Li, HW and Guo, GC and Han, ZF}, title = {Practical non-Poissonian light source for passive decoy state quantum key distribution.}, journal = {Optics letters}, volume = {35}, number = {20}, pages = {3393-3395}, doi = {10.1364/OL.35.003393}, pmid = {20967077}, issn = {1539-4794}, abstract = {Passive decoy state quantum key distribution (QKD) has enormous potential in high-speed applications. In this Letter, an intrinsic-stable non-Poissonian light source was implemented with Faraday mirrors and could be a crucial element in realizing passive decoy state QKD. The stable g((2))(0) was obtained through a Hanbury Brown-Twiss experiment, and the results fit well with the theoretical value according to Curty et al.'s theory [Opt. Lett.34, 3238 (2009)].}, } @article {pmid20964967, year = {2010}, author = {Deleu, PA and Pod, H and Leemrijse, T and Birch, I and Vande Berg, B and Bevernage, BD}, title = {Reliability of the Maestro radiographic measuring tool.}, journal = {Foot & ankle international}, volume = {31}, number = {10}, pages = {884-891}, doi = {10.3113/FAI.2010.0884}, pmid = {20964967}, issn = {1071-1007}, mesh = {Adult ; Female ; Forefoot, Human/*anatomy & histology/*diagnostic imaging ; Humans ; Male ; Metatarsal Bones/*anatomy & histology/*diagnostic imaging ; Metatarsalgia/diagnostic imaging ; Radiography ; Reference Values ; Reproducibility of Results ; }, abstract = {INTRODUCTION: Maestro et al. presented a detailed preoperative measuring and classification technique for the forefoot. The purpose of this paper was to determine if the PACS system will allow the Maestro measuring technique and classification system to be reliable and precise.

MATERIALS AND METHODS: This radiographic study was conducted on 73 subjects (36 females, 37 males, age 30.4 ± 9.9) who had given informed consent. The geometrical progression was measured for each foot of each subject by the two observers according to the measuring methodology of Maestro. The intraclass correlation coefficient (ICC), and the 95% lower confidence limit (95% LCL) were calculated for the geometrical progression variables of the lesser metatarsals. Once the feet were classified by each observer, the accordance in classification of the feet was analyzed between the two observers.

RESULTS: The radiographic measuring technique of Maestro was a reliable method for analyzing the mathematical progression of the lesser metatarsals through the use of the PACS system. A 92.6% concordance in the classification of the radiological forefoot morphotypes was found between the two observers.

CONCLUSION: We found Maestro et al.'s measuring technique and classification system precise and reproducible using PACS digital radiographs. It is hoped that utilization of this technique will lead to better forefoot outcomes and patient satisfaction.}, } @article {pmid20961545, year = {2011}, author = {Thompson, C}, title = {Commentary on Aitken et al.'s (2010) 'Comparison of 'think aloud' and observation as data collection methods in the study of decision making regarding sedation in intensive care patients'.}, journal = {International journal of nursing studies}, volume = {48}, number = {3}, pages = {401-402}, doi = {10.1016/j.ijnurstu.2010.08.001}, pmid = {20961545}, issn = {1873-491X}, mesh = {*Critical Care ; *Data Collection ; *Decision Making ; Humans ; Hypnotics and Sedatives/*administration & dosage ; }, } @article {pmid20939352, year = {2010}, author = {Wang, XP and Li, B}, title = {[Analysis of 27 mineral elements in the rice samples collected from China and Japan by using ICP-OES and ICP-MS].}, journal = {Guang pu xue yu guang pu fen xi = Guang pu}, volume = {30}, number = {8}, pages = {2260-2264}, pmid = {20939352}, issn = {1000-0593}, mesh = {China ; Japan ; Magnesium ; Minerals/*analysis ; Oryza/*chemistry ; *Spectrum Analysis ; }, abstract = {Based on microwave-assisted decomposition and dry ashing methods, the concentrations of Al, As, B, Ba, Ca, Cd, Co, Cr, Cs, Cu, Fe, Hg, K, Mg, Mn, Mo, Na, Ni, P, Pb, Rb, S, Se, Sr, T1, V and Zn in sixteen Chinese rice samples and eleven Japanese rice samples were analysed by using ICP-OES and ICP-MS, and a biological standard reference material rice (GBW10010) was used to verify the accuracy and the precision of analytical method. It was demonstrated that ICP-MS equipped with a collision cell technique can be successfully used for reducing polyatomic interferences in the detection of elements with low m/z ratios. Compared with those in Japanese rice samples, the concentrations of Al, S and Sr in Chinese rice samples are significantly high, and the concentrations of B, Cd, Cs, Mg, Mo, P, Pb and Zn in Chinese rice samples are much lower (P < 0.05). The Ward's method of cluster analysis applied to the concentrations of 26 elements except T1 whose concentration is below the detection limit exhibited the ability to effectively differentiate Chinese rice samples from Japanese rice samples. Moreover, it was found that the concentrations of magnesium correlate very well with the concentrations of phosphorus in all rice samples, with the correlation coefficient being as high as 0.9552.}, } @article {pmid20936741, year = {2010}, author = {Shang, X and Yen, MR and Gaber, MW}, title = {Studies of biaxial mechanical properties and nonlinear finite element modeling of skin.}, journal = {Molecular & cellular biomechanics : MCB}, volume = {7}, number = {2}, pages = {93-104}, pmid = {20936741}, issn = {1556-5297}, mesh = {Animals ; Anisotropy ; Biomechanical Phenomena ; Elasticity ; Finite Element Analysis ; In Vitro Techniques ; Male ; *Models, Biological ; Nonlinear Dynamics ; Rats ; Rats, Sprague-Dawley ; *Skin Physiological Phenomena ; Stress, Mechanical ; }, abstract = {The objective of this research is to conduct mechanical property studies of skin from two individual but potentially connected aspects. One is to determine the mechanical properties of the skin experimentally by biaxial tests, and the other is to use the finite element method to model the skin properties. Dynamic biaxial tests were performed on 16 pieces of abdominal skin specimen from rats. Typical biaxial stress-strain responses show that skin possesses anisotropy, nonlinearity and hysteresis. To describe the stress-strain relationship in forms of strain energy function, the material constants of each specimen were obtained and the results show a high correlation between theory and experiments. Based on the experimental results, a finite element model of skin was built to model the skin's special properties including anisotropy and nonlinearity. This model was based on Arruda and Boyce's eight-chain model and Bischoff et al.'s finite element model of skin. The simulation results show that the isotropic, nonlinear eight-chain model could predict the skin's anisotropic and nonlinear responses to biaxial loading by the presence of an anisotropic prestress state.}, } @article {pmid20932019, year = {2010}, author = {Rothenberger, A and Shafaei-Fallah, M and Kanatzidis, MG}, title = {Aluminosilicate relatives: Chalcogenoaluminogermanates Rb(3)(AlQ(2))(3)(GeQ(2))(7) (Q = S, Se).}, journal = {Inorganic chemistry}, volume = {49}, number = {21}, pages = {9749-9751}, doi = {10.1021/ic101627v}, pmid = {20932019}, issn = {1520-510X}, abstract = {The new compounds Rb(3)(AlQ(2))(3)(GeQ(2))(7) [Q = S (1), Se (2)] feature the 3D anionic open framework [(AlQ(2))(3)(GeQ(2))(7)](3-) in which aluminum and germanium share tetrahedral coordination sites. Rb ions are located in channels formed by the connection of 8, 10, and 16 (Ge/Al)S(4) tetrahedra. The isostructural sulfur and selenium derivatives crystallize in the space group P2(1)/c. 1: a = 6.7537(3) Å, b = 37.7825(19) Å, c = 6.7515(3) Å, and β = 90.655(4)°. 2: a = 7.0580(5) Å, b = 39.419(2) Å, c = 7.0412(4) Å, β = 90.360(5)°, and Z = 2 at 190(2) K. The band gaps of the congruently melting chalcogenogermanates are 3.1 eV (1) and 2.4 eV (2).}, } @article {pmid20854005, year = {2010}, author = {Finn, B}, title = {Ending on a high note: adding a better end to effortful study.}, journal = {Journal of experimental psychology. Learning, memory, and cognition}, volume = {36}, number = {6}, pages = {1548-1553}, pmid = {20854005}, issn = {1939-1285}, support = {R01 MH060637/MH/NIMH NIH HHS/United States ; R01-MH60637/MH/NIMH NIH HHS/United States ; }, mesh = {Analysis of Variance ; Choice Behavior/physiology ; Emotions/*physiology ; Female ; Humans ; Judgment/physiology ; Learning/*physiology ; Male ; Memory/*physiology ; Neuropsychological Tests ; *Pleasure-Pain Principle ; Prospective Studies ; Students ; Universities ; Vocabulary ; }, abstract = {Remembered utility is the retrospective evaluation about the pleasure and pain associated with a past experience. It has been shown to influence prospective choices about whether to repeat or to avoid similar situations in the future (D. Kahneman 2000; D. Kahneman, D. L. Fredrickson, C. A. Schreiber, & D. A. Redelmeier, 1993). Evaluations about our hedonic past often disregard the duration of the experience and are influenced more by the peak and the final levels of discomfort (B. L. Fredrickson & D. Kahneman, 1993). Two experiments explored the remembered discomfort of an effortful learning experience and the influence of this evaluation on prospective study choices. The design of the studies mimicked D. Kahneman et al.'s (1993) cold-pressor study, but used an exceptionally challenging learning experience in place of the painful experience of submerging one's hand in ice water. An extremely effortful study episode extended by a more moderate interval was preferred to a shorter, unextended interval, despite better test performance following the shorter interval. Future study choices reflected this preference. These findings suggest that the act of acquiring knowledge has value in the learning process.}, } @article {pmid20852726, year = {2010}, author = {Smith, RE}, title = {What Costs Do Reveal and Moving Beyond the Cost Debate: Reply to Einstein and McDaniel (in press).}, journal = {Journal of experimental psychology. Learning, memory, and cognition}, volume = {36}, number = {4}, pages = {1089-1095}, pmid = {20852726}, issn = {1939-1285}, support = {SC1 AG034965/AG/NIA NIH HHS/United States ; }, abstract = {Einstein et al., (2005) predicted no cost to an ongoing task when a prospective memory task meet certain criteria. Smith et al. (2007) used prospective memory tasks that met these criteria and found a cost to the ongoing task, contrary to Einstein et al.'s prediction. Einstein and McDaniel (in press) correctly note that there are limitations to using ongoing task performance as a measure of the processes that contribute to prospective memory performance, however, the alternatives suggested by Einstein and McDaniel all focus on ongoing task performance and therefore do not move beyond the cost debate. This article describes why the Smith et al. findings are important, provides recommendations for issues to consider when investigating cost, and discusses individual cost measures. Finally, noting the blurry distinction between Einstein and McDaniel's description of the reflexive associative processes and preparatory attentional processes and difficulties in extending the multiprocess view to nonlaboratory tasks, suggestions are made for moving beyond the cost debate.}, } @article {pmid20850602, year = {2010}, author = {Halayem, S and Bouden, A and Halayem, MB and Tabbane, K and Amado, I and Krebs, MO}, title = {[Neurological soft signs in pervasive developmental disorders].}, journal = {L'Encephale}, volume = {36}, number = {4}, pages = {307-313}, doi = {10.1016/j.encep.2009.12.012}, pmid = {20850602}, issn = {0013-7006}, mesh = {Adolescent ; Child ; Child Development Disorders, Pervasive/*diagnosis/psychology ; Comorbidity ; Female ; Humans ; Intelligence ; Male ; Motor Skills Disorders/*diagnosis/psychology ; Nervous System Diseases/*diagnosis/psychology ; Neurologic Examination/*methods ; }, abstract = {BACKGROUND: Many studies have focused on specific motor signs in autism and Asperger's syndrome, but few has been published on the complete range of neurological soft signs (NSS) in children with pervasive developmental disorder (PDD). Scarce are the studies evaluating NSS in children suffering from PDD not otherwise specified (PDDNOS).

METHODS: This study compared performance of 11 autistic children (AD) and 10 children with PDDNOS, with controls matched on age, sex and cognitive performance on Krebs et al.'s NSS scale. Because of the duration of the assessments and specific difficulties encountered in managing some items, an adaptation of the scale had to be made during a pilot study with the agreement of the author. To be eligible, patients had to meet the following inclusion criteria: an age range of 6-16 years, a diagnosis of autistic disorder or PDDNOS based on the DSM IV criteria (American Psychiatric Association 1994). The autism diagnostic interview-revised (ADI-R) was used in order to confirm the diagnosis and to evaluate the association of the symptoms to the severity of the NSS. The childhood autism rating scale (CARS) was completed for the patients in order to evaluate symptoms at the time of the NSS examination. Cognitive ability was assessed with Raven's progressive matrices. Were excluded patients with: history of cerebral palsy, congenital anomaly of the central nervous system, epilepsy, known genetic syndrome, tuberous sclerosis, neurofibromatosis, antecedent of severe head trauma, Asperger's syndrome, obvious physical deformities or sensory deficits that would interfere with neurological assessment, deep mental retardation and recent or chronic substance use or abuse. Healthy controls shared the same exclusion criteria, with no personal history of neurological, psychiatric disorder or substance abuse, no family history of psychiatric disorder and normal or retardation in schooling. All study procedures were approved by the local Ethics Committee (Comité d'éthique, Razi Hospital), according to the declaration of Helsinki.

RESULTS: There was no difference between patients and controls with respect to sex, age and cognitive function. All children had an IQ higher than 81. Significant differences were found between AD children and control group in the motor integration function and sensory integration function. Different NSS scores were significantly higher in the PDDNOS group than in controls: the total scores, motor coordination, motor integration function, sensory integration and abnormal movements. Lower performance in motor coordination skills was associated with higher ADI-R communication score in the AD group. No relationship was found between NSS and CARS' total sore.

CONCLUSION: This study confirms the impaired neurological functioning in autistic as well as PDDNOS children. The association of motor impairment with autistic symptoms highlights the argument that motor control problems can be part of the autism spectrum disorders. The lack of relationship between NSS and intellectual aptitude in the clinical sample provides new elements for the neurodevelopment model of the autism spectrum.}, } @article {pmid20833104, year = {2010}, author = {Khajouei, R and Peek, N and Wierenga, PC and Kersten, MJ and Jaspers, MW}, title = {Effect of predefined order sets and usability problems on efficiency of computerized medication ordering.}, journal = {International journal of medical informatics}, volume = {79}, number = {10}, pages = {690-698}, doi = {10.1016/j.ijmedinf.2010.08.001}, pmid = {20833104}, issn = {1872-8243}, mesh = {Cross-Over Studies ; *Efficiency, Organizational ; *Medical Order Entry Systems ; }, abstract = {OBJECTIVES: To study the effect of predefined order sets on the efficiency of computerized medication ordering, and to analyze the effect of different types of usability problems on ordering efficiency.

METHODS: Crossover study to comparing the efficiency of two methods of ordering (with and without use of predefined order sets) in a laboratory setting using a computerized physician order entry system (CPOE). The excess number of mouse clicks and keystrokes (the difference in number of mouse clicks and keystrokes needed by each physician and the minimally required numbers to accomplish the ordering tasks) for each method was measured and per physician, occurrences of usability problems during the task sessions were recorded. Observed usability problems were categorized using Zhang et al.'s heuristic principles of good user interface design. The effect of different types of usability problems on the excess number of mouse clicks and keystrokes was statistically analyzed.

RESULTS: The median excess number of mouse clicks and keystrokes needed by physicians was 6.2 times lower in the method with predefined order sets (p<0.01). The excess number of mouse clicks and keystrokes was significantly increased by vague and erroneous system messages with a factor of 2.62 (95% CI 2.24-3.07), the use of unfamiliar language and terminology by a factor of 1.28 (95% CI 1.14-1.43), and non-informative system feedback by a factor of 1.15 (95% CI 1.03-1.28), respectively. Other categories of usability problems had little influence on ordering efficiency.

CONCLUSIONS: Predefined order sets can improve the efficiency of computerized ordering by reducing the excess number of mouse clicks and keystrokes. However, the efficiency of computerized ordering can be significantly impaired by usability problems due to vague and incorrect system messages, unfamiliar language, and non-informative system feedback.}, } @article {pmid20827591, year = {2010}, author = {Jiao, S and Bailey, CP and Zhang, S and Ladunga, I}, title = {Probabilistic peak calling and controlling false discovery rate estimations in transcription factor binding site mapping from ChIP-seq.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {674}, number = {}, pages = {161-177}, doi = {10.1007/978-1-60761-854-6_10}, pmid = {20827591}, issn = {1940-6029}, mesh = {Binding Sites ; *Chromatin Immunoprecipitation ; False Positive Reactions ; GA-Binding Protein Transcription Factor/metabolism ; Humans ; Internet ; Jurkat Cells ; Probability ; Regulatory Sequences, Nucleic Acid/genetics ; Reproducibility of Results ; *Sequence Analysis, DNA ; Software ; Transcription Factors/*metabolism ; }, abstract = {Localizing the binding sites of regulatory proteins is becoming increasingly feasible and accurate. This is due to dramatic progress not only in chromatin immunoprecipitation combined by next-generation sequencing (ChIP-seq) but also in advanced statistical analyses. A fundamental issue, however, is the alarming number of false positive predictions. This problem can be remedied by improved peak calling methods of twin peaks, one at each strand of the DNA, kernel density estimators, and false discovery rate estimations based on control libraries. Predictions are filtered by de novo motif discovery in the peak environments. These methods have been implemented in, among others, Valouev et al.'s Quantitative Enrichment of Sequence Tags (QuEST) software tool. We demonstrate the prediction of the human growth-associated binding protein (GABPalpha) based on ChIP-seq observations.}, } @article {pmid20822523, year = {2010}, author = {Ducray, F and de Reyniès, A and Chinot, O and Idbaih, A and Figarella-Branger, D and Colin, C and Karayan-Tapon, L and Chneiweiss, H and Wager, M and Vallette, F and Marie, Y and Rickman, D and Thomas, E and Delattre, JY and Honnorat, J and Sanson, M and Berger, F}, title = {An ANOCEF genomic and transcriptomic microarray study of the response to radiotherapy or to alkylating first-line chemotherapy in glioblastoma patients.}, journal = {Molecular cancer}, volume = {9}, number = {}, pages = {234}, pmid = {20822523}, issn = {1476-4598}, mesh = {Antineoplastic Agents, Alkylating/pharmacology/*therapeutic use ; Cyclin-Dependent Kinase Inhibitor p16/genetics ; DNA Methylation/drug effects ; Glioblastoma/*drug therapy/genetics/*radiotherapy ; Humans ; Immunohistochemistry ; In Vitro Techniques ; *Oligonucleotide Array Sequence Analysis ; Promoter Regions, Genetic/genetics ; Retrospective Studies ; }, abstract = {BACKGROUND: The molecular characteristics associated with the response to treatment in glioblastomas (GBMs) remain largely unknown. We performed a retrospective study to assess the genomic characteristics associated with the response of GBMs to either first-line chemotherapy or radiation therapy. The gene expression (n = 56) and genomic profiles (n = 67) of responders and non-responders to first-line chemotherapy or radiation therapy alone were compared on Affymetrix Plus 2 gene expression arrays and BAC CGH arrays.

RESULTS: According to Verhaak et al.'s classification system, mesenchymal GBMs were more likely to respond to radiotherapy than to first-line chemotherapy, whereas classical GBMs were more likely to respond to first-line chemotherapy than to radiotherapy. In patients treated with radiation therapy alone, the response was associated with differential expression of microenvironment-associated genes; the expression of hypoxia-related genes was associated with short-term progression-free survival (< 5 months), whereas the expression of immune genes was associated with prolonged progression-free survival (> 10 months). Consistently, infiltration of the tumor by both CD3 and CD68 cells was significantly more frequent in responders to radiotherapy than in non-responders. In patients treated with first-line chemotherapy, the expression of stem-cell genes was associated with resistance to chemotherapy, and there was a significant association between response to treatment and p16 locus deletions. Consistently, in an independent data set of patients treated with either radiotherapy alone or with both radiotherapy and adjuvant chemotherapy, we found that patients with the p16 deletion benefited from adjuvant chemotherapy regardless of their MGMT promoter methylation status, whereas in patients without the p16 deletion, this benefit was only observed in patients with a methylated MGMT promoter.

CONCLUSION: Differential expression of microenvironment genes and p16 locus deletion are associated with responses to radiation therapy and to first-line chemotherapy, respectively, in GBM. Recently identified transcriptomic subgroups of GBMs seem to respond differently to radiotherapy and to first-line chemotherapy.}, } @article {pmid20822220, year = {2010}, author = {Hooper, SR and Roberts, J and Sideris, J and Burchinal, M and Zeisel, S}, title = {Longitudinal predictors of reading and math trajectories through middle school for African American versus Caucasian students across two samples.}, journal = {Developmental psychology}, volume = {46}, number = {5}, pages = {1018-1029}, doi = {10.1037/a0018877}, pmid = {20822220}, issn = {1939-0599}, mesh = {*Black or African American ; Age Factors ; Child ; Child, Preschool ; *Cross-Cultural Comparison ; Databases, Factual/statistics & numerical data ; Female ; Hispanic or Latino ; Humans ; Longitudinal Studies ; Male ; *Mathematics ; Predictive Value of Tests ; *Reading ; Sample Size ; *Schools ; *White People ; }, abstract = {This study's primary purpose was to examine the relative contribution of social-behavioral predictors to reading and math skills. The study expands on Duncan et al.'s (2007) work by using longitudinal methodology from the National Institute of Child Health and Human Development's Study of Child Care and Youth Development (SECCYD) and the Early Childhood Longitudinal Study, Kindergarten Class of 1998-1999 (ECLS-K) databases, and by focusing on potential differences in patterns of early predictors of later reading and math trajectories for African American versus Caucasian students. Predictor measures were selected at kindergarten, and the outcomes included standardized reading and math scores obtained from Grades 1, 3, 5, and 9 for the SECCYD sample, and Grades 3, 5, and 8 for the ECLS-K sample. Consistent with Duncan et al.'s findings, results reflect the relative contributions of early reading and math skills to later functioning in these respective academic domains for both samples, and there are indications for the importance of early expressive language skills to both reading and math in the SECCYD sample. Findings related to the power of social-behavioral predictors, however, are not consistent across samples. Although the SECCYD sample evidenced no such predictors, several interactions in the ECLS-K sample suggested the moderating effects of early ratings of aggressive behaviors and internalizing behaviors on later reading and math for African American students. The moderating effects of early teacher ratings of attention and internalizing behaviors for African American students as compared with Caucasian students in later math growth also were noted. The importance of early social-behavioral functions as related to later academic skills remains an important area of inquiry.}, } @article {pmid20822219, year = {2010}, author = {Grissmer, D and Grimm, KJ and Aiyer, SM and Murrah, WM and Steele, JS}, title = {Fine motor skills and early comprehension of the world: two new school readiness indicators.}, journal = {Developmental psychology}, volume = {46}, number = {5}, pages = {1008-1017}, doi = {10.1037/a0020104}, pmid = {20822219}, issn = {1939-0599}, mesh = {Achievement ; Age Factors ; Child ; *Child Development ; Comprehension/*physiology ; Humans ; Longitudinal Studies ; Motor Skills/*physiology ; Predictive Value of Tests ; *Reading ; *Schools ; Science ; Sensitivity and Specificity ; }, abstract = {Duncan et al. (2007) presented a new methodology for identifying kindergarten readiness factors and quantifying their importance by determining which of children's developing skills measured around kindergarten entrance would predict later reading and math achievement. This article extends Duncan et al.'s work to identify kindergarten readiness factors with 6 longitudinal data sets. Their results identified kindergarten math and reading readiness and attention as the primary long-term predictors but found no effects from social skills or internalizing and externalizing behavior. We incorporated motor skills measures from 3 of the data sets and found that fine motor skills are an additional strong predictor of later achievement. Using one of the data sets, we also predicted later science scores and incorporated an additional early test of general knowledge of the social and physical world as a predictor. We found that the test of general knowledge was by far the strongest predictor of science and reading and also contributed significantly to predicting later math, making the content of this test another important kindergarten readiness indicator. Together, attention, fine motor skills, and general knowledge are much stronger overall predictors of later math, reading, and science scores than early math and reading scores alone.}, } @article {pmid20807676, year = {2011}, author = {Zhou, Y and Cameron, E and Forbes, G and Humphris, G}, title = {Systematic review of the effect of dental staff behaviour on child dental patient anxiety and behaviour.}, journal = {Patient education and counseling}, volume = {85}, number = {1}, pages = {4-13}, doi = {10.1016/j.pec.2010.08.002}, pmid = {20807676}, issn = {1873-5134}, mesh = {Child ; Child Behavior ; Child, Preschool ; Dental Anxiety/*prevention & control ; *Dental Auxiliaries ; *Dental Care for Children ; *Dentist-Patient Relations ; Humans ; Patient Compliance ; *Professional-Patient Relations ; }, abstract = {OBJECTIVES: To review the literature, of the past 30 years, on the effects of dental staff behaviour on the anxiety and behaviour of child dental patients; especially to determine staff behaviours that reduce anxiety and encourage cooperation of children.

METHODS: A systematic literature review was conducted using PubMed, Web of Science, The Cochrane Library, PsycINFO, Embase and CINAHL.

RESULTS: Initial search returned 31 publications of which 11 fulfilled the criteria for review. Among seven studies that measured anxiety, four used validated measures. Five observational studies coded behaviour using Weinstein et al.'s (1982) coding scheme [1]. An empathic working style and appropriate level of physical contact accompanied by verbal reassurance was found to reduce fear-related behaviours in children. Findings regarding positive reinforcement and dentists' experience increasing cooperative behaviour were inconsistent.

CONCLUSIONS: Measures for anxiety and behaviour varied across studies. Relationships between certain dental staff behaviours and child anxiety/behaviour were reported. However, limited work was identified and research using improved sampling, measurement and statistical approach is required.

PRACTICE IMPLICATIONS: Understanding what routine clinical behaviour of dental staff affects children's dental anxiety/behaviour will inform investigators of how children comply and help staff be aware the significance of their daily behaviour on treatment success.}, } @article {pmid20806732, year = {2010}, author = {Melis, M}, title = {Dr. Melis' comments on Tecco, et al.'s article in the January 2010 issue of CRANIO.}, journal = {Cranio : the journal of craniomandibular practice}, volume = {28}, number = {3}, pages = {153; discussion 153-4}, pmid = {20806732}, issn = {0886-9634}, mesh = {Humans ; Joint Dislocations/therapy ; Mandibular Advancement/instrumentation/methods ; *Occlusal Splints ; *Orthodontic Appliances ; Temporomandibular Joint Disc/pathology ; Temporomandibular Joint Disorders/*therapy ; }, } @article {pmid20805723, year = {2010}, author = {Carchietti, E and Berlot, G}, title = {Reply to Dr Lockey et al.'s remarks on prehospital thoracostomy.}, journal = {European journal of emergency medicine : official journal of the European Society for Emergency Medicine}, volume = {17}, number = {5}, pages = {305}, doi = {10.1097/MEJ.0b013e3283298891}, pmid = {20805723}, issn = {1473-5695}, mesh = {Emergency Medical Services/*methods ; Humans ; Pneumothorax/*surgery ; Thoracic Injuries/surgery ; Thoracostomy/*methods ; Time Factors ; }, } @article {pmid20800012, year = {2011}, author = {Fountoulakis, KN and Möller, HJ}, title = {Efficacy of antidepressants: a re-analysis and re-interpretation of the Kirsch data.}, journal = {The international journal of neuropsychopharmacology}, volume = {14}, number = {3}, pages = {405-412}, doi = {10.1017/S1461145710000957}, pmid = {20800012}, issn = {1469-5111}, mesh = {Antidepressive Agents/*therapeutic use ; Data Interpretation, Statistical ; Depression/*drug therapy ; Depressive Disorder/*drug therapy ; Depressive Disorder, Major/*drug therapy ; Humans ; Meta-Analysis as Topic ; Psychiatric Status Rating Scales ; Psychometrics ; Randomized Controlled Trials as Topic ; Research Design ; Treatment Outcome ; }, abstract = {Recently there has been much debate on the true usefulness of antidepressant therapy especially after the publication of a meta-analysis by Kirsch et al. (PLoS Medicine 2008, 5, e45). The aim of the current paper was to recalculate and re-interpret the data of that study. Effect-size and mean-score changes were calculated for each agent separately as well as pooled effect sizes and mean changes on the basis of the data reported by Kirsch et al. The weighted mean improvement was (depending on the method of calculation) 10.04 or 10.16 points on the Hamilton Depression Rating Scale (HAMD) in the drug groups, instead of 9.60, and thus the correct drug-placebo difference is 2.18 or 2.68 instead of 1.80. Kirsch et al. failed to report that that the change in HAMD score was 3.15 or 3.47 points for venlafaxine and 3.12 or 3.22 for paroxetine, which are above the NICE threshold. Still the figures for fluoxetine and nefazodone are low. Thus it seems that the Kirsch et al.'s meta-analysis suffered from important flaws in the calculations; reporting of the results was selective and conclusions unjustified and overemphasized. Overall the results suggest that although a large percentage of the placebo response is due to expectancy this is not true for the active drug and effects are not additive. The drug effect is always present and is unrelated to depression severity, while this is not true for placebo.}, } @article {pmid20728984, year = {2010}, author = {Soni, CR and Kumar, G and Sahota, P and Miller, DC and Litofsky, NS}, title = {Metastases to Meckel's cave: report of two cases and comparative analysis of malignant tumors with meningioma and schwannoma of Meckel's cave.}, journal = {Clinical neurology and neurosurgery}, volume = {112}, number = {10}, pages = {927-932}, doi = {10.1016/j.clineuro.2010.07.019}, pmid = {20728984}, issn = {1872-6968}, mesh = {Aged ; Carcinoma, Squamous Cell/pathology ; Craniotomy ; Diagnosis, Differential ; Fatal Outcome ; Female ; Humans ; Immunohistochemistry ; Magnetic Resonance Imaging ; Male ; Meningioma/pathology/*secondary/*surgery ; Middle Aged ; Neurilemmoma/pathology/*secondary/*surgery ; Nose Neoplasms/pathology ; Skull Base Neoplasms/pathology/*secondary/*surgery ; Temporal Bone/*pathology ; }, abstract = {OBJECTIVE: To investigate clinical characteristics of patients with malignant tumors of Meckel's cave with two illustrative cases. A comparative analysis of clinical features of malignant tumors of Meckel's cave with meningioma and schwannoma of Meckel's cave is discussed.

METHODS: We report two cases of malignant tumors involving Meckel's cave. We identified 19 additional cases of malignant tumors of Meckel's cave in the literature. We analyzed the symptoms, results of neurological and radiographic examination, pre-operative diagnosis and final diagnosis of these tumors. Our findings were then compared with well described case series of meningioma and schwannoma involving Meckel's cave.

RESULTS: Of the 21 patients with malignant tumor involving Meckel's cave, 76% (16/21) had pain, 67% (14/21) had paraesthesia, 89% (17/21) had objective evidence of trigeminal sensory involvement and 42% (8/21) had objective evidence of trigeminal motor involvement. In contrast, of patients with trigeminal schwannomas [1], only 23% presented with pain, 36% with paraesthesia, 74% with objective evidence of trigeminal involvement and 42% with trigeminal motor involvement. Pain and paraesthesia were seen more often in malignant tumors. In Delfini et al.'s [2] series of meningiomas involving Meckel's cave, 81% of patients presented with pain, 25% with paraesthesia, 63% with trigeminal sensory deficits and only 13% with trigeminal motor involvement. Patients with malignant tumors were more likely to be older, and have paraesthesia in comparison with patients with meningioma.

CONCLUSION: Subtle clinical clues may help differentiate malignant from benign involvement of Meckel's cave. We emphasize the need to thoroughly investigate patients early for a possible primary as well as metastases, in those found to have a lesion in the Meckel's cave.}, } @article {pmid20702864, year = {2010}, author = {Klauer, KC and Kellen, D}, title = {Toward a complete decision model of item and source recognition: A discrete-state approach.}, journal = {Psychonomic bulletin & review}, volume = {17}, number = {4}, pages = {465-478}, pmid = {20702864}, issn = {1531-5320}, mesh = {*Attention ; Cognition ; *Decision Support Techniques ; Discrimination, Psychological ; Humans ; Individuality ; Judgment ; *Models, Psychological ; Models, Statistical ; ROC Curve ; *Recognition, Psychology ; Signal Detection, Psychological ; }, abstract = {In source-monitoring experiments, participants study items from two sources (A and B). At test, they are presented Source A items, Source B items, and new items. They are asked to decide whether a test item is old or new (item memory) and whether it is a Source A or a Source B item (source memory). Hautus, Macmillan, and Rotello (2008) developed models, couched in a bivariate signal detection framework, that account for item and source memory across several data sets collected in a confidence-rating response format. The present article enlarges the set of candidate models with a discrete-state model. The model is a straightforward extension of Bayen, Murnane, and Erdfelder's (1996) multinomial model of source discrimination to confidence ratings. On the basis of the evaluation criteria adopted by Hautus et al., it provides a better account of the data than do Hautus et al.'s models.}, } @article {pmid20695718, year = {2010}, author = {Bootsma, RJ and Fernandez, L and Morice, AH and Montagne, G}, title = {Top-level players' visual control of interceptive actions: Bootsma and van Wieringen (1990) 20 years later.}, journal = {Journal of experimental psychology. Human perception and performance}, volume = {36}, number = {4}, pages = {1056-63; discussion 1064-6}, doi = {10.1037/a0019327}, pmid = {20695718}, issn = {1939-1277}, mesh = {Acceleration ; *Athletic Performance ; *Attention ; Distance Perception ; Humans ; Isometric Contraction ; *Motion Perception ; Motor Skills ; Orientation ; Professional Competence ; *Psychomotor Performance ; Psychophysics ; *Reaction Time ; Sensory Deprivation ; *Space Perception ; Tennis/*psychology ; Time Perception ; }, abstract = {Using a two-step approach, Van Soest et al. (2010) recently questioned the pertinence of the conclusions drawn by Bootsma and Van Wieringen (1990) with respect to the visual regulation of an exemplary rapid interceptive action: the attacking forehand drive in table tennis. In the first step, they experimentally compared the movement behaviors of their participants under conditions with and without vision available during the execution of the drive. In the second step, through simulation they evaluated the extent to which a preprogrammed pattern of muscle stimulation acting on the dynamical characteristics of the musculoskeletal system could explain the patterns of movement observed, including the phenomena of kinematic convergence and compensatory variability. In this contribution, we show how methodological and conceptual shortcomings, pertaining to both parts of Van Soest et al.'s study, severely limit the impact of their findings. We argue that their conclusion-denying the possibility of visual regulation of rapid interceptive actions-cannot be upheld in the light of the existing evidence, while Bootsma and Van Wieringen's conclusion-in favor of the visual regulation of rapid interceptive actions in top-level players- still holds strong, even after 20 years. Irrespective of the trends of the moment, we suggest that both appropriate experimentation and principled theorization need to be deployed before a model-based predictive architecture can be considered as a serious alternative to a (more parsimonious) information-based control architecture.}, } @article {pmid20682088, year = {2010}, author = {Ehrensperger, MM and Berres, M and Taylor, KI and Monsch, AU}, title = {Early detection of Alzheimer's disease with a total score of the German CERAD.}, journal = {Journal of the International Neuropsychological Society : JINS}, volume = {16}, number = {5}, pages = {910-920}, doi = {10.1017/S1355617710000822}, pmid = {20682088}, issn = {1469-7661}, mesh = {Aged ; Aged, 80 and over ; Alzheimer Disease/complications/*diagnosis/epidemiology ; Area Under Curve ; Cognition Disorders/diagnosis/etiology ; Cross-Sectional Studies ; Disease Progression ; Early Diagnosis ; Female ; Germany/epidemiology ; Humans ; Logistic Models ; Longitudinal Studies ; Male ; Middle Aged ; *Neuropsychological Tests ; Reproducibility of Results ; }, abstract = {The goal of the present study was to evaluate the diagnostic discriminability of three different global scores for the German version of the Consortium to Establish a Registry on Alzheimer's Disease-Neuropsychological Assessment Battery (CERAD-NAB). The CERAD-NAB was administered to 1100 healthy control participants [NC; Mini-Mental State Examination (MMSE) mean = 28.9] and 352 patients with very mild Alzheimer's disease (AD; MMSE mean = 26.1) at baseline and subsets of participants at follow-up an average of 2.4 (NC) and 1.2 (AD) years later. We calculated the following global scores: Chandler et al.'s (2005) score (summed raw scores), logistic regression on principal components analysis scores (PCA-LR), and logistic regression on demographically corrected CERAD-NAB variables (LR). Correct classification rates (CCR) were compared with areas under the receiver operating characteristics curves (AUC). The CCR of the LR score (AUC = .976) exceeded that of the PCA-LR, while the PCA-LR (AUC = .968) and Chandler (AUC = .968) scores performed comparably. Retest data improved the CCR of the PCA-LR and Chandler (trend) scores. Thus, for the German CERAD-NAB, Chandler et al.'s total score provided an effective global measure of cognitive functioning, whereby the inclusion of retest data tended to improve correct classification of individual cases.}, } @article {pmid20682056, year = {2010}, author = {Bi, K and Bogart, JP}, title = {Time and time again: unisexual salamanders (genus Ambystoma) are the oldest unisexual vertebrates.}, journal = {BMC evolutionary biology}, volume = {10}, number = {}, pages = {238}, pmid = {20682056}, issn = {1471-2148}, mesh = {Ambystoma/classification/*genetics ; Animals ; Bayes Theorem ; *Biological Evolution ; Cytochromes b/genetics ; DNA, Mitochondrial/genetics ; *Genome, Mitochondrial ; Haplotypes ; Kentucky ; *Phylogeny ; Sequence Analysis, DNA ; }, abstract = {BACKGROUND: The age of unisexual salamanders of the genus Ambystoma is contentious. Recent and ancient evolutionary histories of unisexual Ambystoma were proposed by a few separate studies that constructed phylogenies using mitochondrial DNA markers (cytochrome b gene vs. non-coding region). In contrast to other studies showing that unisexual Ambystoma represent the most ancient unisexual vertebrates, a recent study by Robertson et al. suggests that this lineage has a very recent origin of less than 25,000 years ago.

RESULTS: We re-examined the phylogenetic relationship of the unisexuals to A. barbouri from various populations using both mitochondrial markers as well as the complete mitochondrial genomes of A. barbouri and a unisexual individual from Kentucky. Lineage dating was conducted using BEAST and MultiDivTime on a complete mitochondrial genome phylogeny. Our results support a monophyletic lineage for unisexual Ambystoma that shares its most recent common ancestor with an A. barbouri lineage from western Kentucky. In contrast to the Robertson et al.'s study, no A. barbouri individual shared an identical or almost identical cytochrome b haplotype with any unisexual. Molecular dating supports an early Pliocene origin for the unisexual linage (approximately 5 million years ago). We propose that a unisexual-like cytochrome b numt (or pseudogene) exists in the controversial A. barbouri individuals from Kentucky, which was likely the cause of an erroneous phylogeny and time estimate in Robertson et al.'s study.

CONCLUSION: We reject a recent origin of unisexual Ambystoma and provide strong evidence that unisexual Ambystoma are the most ancient unisexual vertebrates known to exist. The likely presence of an ancient cytochrome b numt in some Kentucky A. barbouri represents a molecular "fossil" reinforcing the hypothesis that these individuals are some of the closest extant relatives to unisexual Ambystoma.}, } @article {pmid20680327, year = {2010}, author = {Baker, L}, title = {Reply to Nolte and Noakes' "comments on Baker et al.'s change in body mass accurately and reliably predicts change in body water after endurance exercise".}, journal = {European journal of applied physiology}, volume = {110}, number = {5}, pages = {1091-1093}, pmid = {20680327}, issn = {1439-6327}, mesh = {Body Water/*physiology ; Body Weight/*physiology ; Exercise/*physiology ; Female ; Hot Temperature ; Humans ; Male ; Physical Endurance/*physiology ; }, } @article {pmid20664749, year = {2010}, author = {Tiwari, HK and Patki, A and Allison, DB}, title = {Within-Cluster Resampling for Analysis of Family Data: Ready for Prime-Time?.}, journal = {Statistics and its interface}, volume = {3}, number = {2}, pages = {169-176}, pmid = {20664749}, issn = {1938-7989}, support = {R21 LM008791/LM/NLM NIH HHS/United States ; R01 ES009912/ES/NIEHS NIH HHS/United States ; R01 GM077490/GM/NIGMS NIH HHS/United States ; R01 DK074842/DK/NIDDK NIH HHS/United States ; R01 DK052431/DK/NIDDK NIH HHS/United States ; U54 CA100949/CA/NCI NIH HHS/United States ; P30 DK056336/DK/NIDDK NIH HHS/United States ; }, abstract = {Hoffman et al. [1] proposed an elegant resampling method for analyzing clustered binary data. The focus of their paper was to perform association tests on clustered binary data using within-cluster-resampling (WCR) method. Follmann et al. [2] extended Hoffman et al.'s procedure more generally with applicability to angular data, combining of p-values, testing of vectors of parameters, and Bayesian inference. Follmann et al. [2] termed their procedure multiple outputation because all "excess" data within each cluster is thrown out multiple times. Herein, we refer to this procedure as WCR-MO. For any statistical test to be useful for a particular design, it must be robust, have adequate power, and be easy to implement and flexible. WCR-MO can be easily extended to continuous data and is a computationally intensive but simple and highly flexible method. Considering family as a cluster, one can apply WCR to familial data in genetic studies. Using simulations, we evaluated WCR-MO's robustness for analysis of a continuous trait in terms of type I error rates in genetic research. WCR-MO performed well at the 5% α-level. However, it provided inflated type I error rates for α-levels less than 5% implying the procedure is liberal and may not be ready for application to genetic studies where α levels used are typically much less than 0.05.}, } @article {pmid20660117, year = {2010}, author = {Ness, RB}, title = {Invited commentary: Population-based human subjects research in the era of enhanced privacy regulation.}, journal = {American journal of epidemiology}, volume = {172}, number = {6}, pages = {648-50; discussion 651-2}, doi = {10.1093/aje/kwq218}, pmid = {20660117}, issn = {1476-6256}, mesh = {Breast Neoplasms/epidemiology ; Confidentiality/*ethics ; Data Collection/*methods ; *Epidemiologic Studies ; Female ; Health Insurance Portability and Accountability Act/legislation & jurisprudence ; Humans ; Patient Selection/*ethics ; Quality of Health Care ; United States/epidemiology ; }, abstract = {Privacy seems to be of increasing public concern, as evidenced by the Health Insurance Portability and Accountability Act (HIPAA) Privacy Rule, a regulatory framework that appears to hinder access to data and thus to limit population-based research. A 2009 Institute of Medicine (IOM) report urged Congress, via the US Department of Health and Human Services (HHS), to develop a new approach to protecting privacy that would not employ the HIPAA Privacy Rule. In an accompanying article in the Journal, Nattinger et al. (Am J Epidemiol. 2010;172(6):637-644) employ one of the constructs recommended in the IOM report: use of a centralized honest broker. Unfortunately, Nattinger et al.'s approach would not be acceptable to all institutional review boards. The IOM report also urged the HHS to reduce variability in interpretations of the HIPAA Privacy Rule by privacy boards through revised and expanded guidance and harmonization. HHS Secretary Kathleen Sebalius has not acted upon any of the IOM report recommendations. The need to remove major barriers to human health research cannot be forgotten. At risk is America's progress in finding solutions to our most pressing health concerns.}, } @article {pmid20628948, year = {2010}, author = {Maticka-Tyndale, E}, title = {Commentary on Nobelius et al.'s "'you still need to give her a token of appreciation': the meaning of the exchange of money in the sexual relationships of out-of-school adolescents in rural southwest Uganda".}, journal = {Journal of sex research}, volume = {47}, number = {5}, pages = {504-506}, doi = {10.1080/00224499.2010.494777}, pmid = {20628948}, issn = {1559-8519}, mesh = {Adolescent ; *Adolescent Behavior/ethnology ; Female ; Gift Giving ; *Health Surveys/methods/standards ; Humans ; *Interpersonal Relations ; Male ; Research Design ; Rural Population ; *Sexual Behavior/ethnology ; Uganda ; }, } @article {pmid20621588, year = {2010}, author = {Rode, G and Cotton, F and Revol, P and Jacquin-Courtois, S and Rossetti, Y and Bartolomeo, P}, title = {Representation and disconnection in imaginal neglect.}, journal = {Neuropsychologia}, volume = {48}, number = {10}, pages = {2903-2911}, doi = {10.1016/j.neuropsychologia.2010.05.032}, pmid = {20621588}, issn = {1873-3514}, mesh = {Aged ; Anisotropy ; Brain/*physiopathology ; Brain Mapping ; Functional Laterality/physiology ; Humans ; Image Processing, Computer-Assisted/methods ; *Imagination ; Magnetic Resonance Imaging/methods ; Male ; Perceptual Disorders/*pathology/physiopathology ; Photic Stimulation/methods ; }, abstract = {Patients with neglect failure to detect, orient, or respond to stimuli from a spatially confined region, usually on their left side. Often, the presence of perceptual input increases left omissions, while sensory deprivation decreases them, possibly by removing attention-catching right-sided stimuli (Bartolomeo, 2007). However, such an influence of visual deprivation on representational neglect was not observed in patients while they were imagining a map of France (Rode et al., 2007). Therefore, these patients with imaginal neglect either failed to generate the left side of mental images (Bisiach & Luzzatti, 1978), or suffered from a co-occurrence of deficits in automatic (bottom-up) and voluntary (top-down) orienting of attention. However, in Rode et al.'s experiment visual input was not directly relevant to the task; moreover, distraction from visual input might primarily manifest itself when representation guides somatomotor actions, beyond those involved in the generation and mental exploration of an internal map (Thomas, 1999). To explore these possibilities, we asked a patient with right hemisphere damage, R.D., to explore visual and imagined versions of a map of France in three conditions: (1) 'imagine the map in your mind' (imaginal); (2) 'describe a real map' (visual); and (3) 'list the names of French towns' (propositional). For the imaginal and visual conditions, verbal and manual pointing responses were collected; the task was also given before and after mental rotation of the map by 180 degrees . R.D. mentioned more towns on the right side of the map in the imaginal and visual conditions, but showed no representational deficit in the propositional condition. The rightward inner exploration bias in the imaginal and visual conditions was similar in magnitude and was not influenced by mental rotation or response type (verbal responses or manual pointing to locations on a map), thus suggesting that the representational deficit was robust and independent of perceptual input in R.D. Structural and diffusion MRI demonstrated damage to several white matter tracts in the right hemisphere and to the splenium of corpus callosum. A second right-brain damaged patient (P.P.), who showed signs of visual but not imaginal neglect, had damage to the same intra-hemispheric tracts, but the callosal connections were spared. Imaginal neglect in R.D. may result from fronto-parietal dysfunction impairing orientation towards left-sided items and posterior callosal disconnection preventing the symmetrical processing of spatial information from long-term memory.}, } @article {pmid20620159, year = {2010}, author = {Ratanabanangkoon, K}, title = {D.A.N. Cook et al.'s account of the immunization of camels is at variance with the 'low dose, low volume multi-site' immunization protocol.}, journal = {Toxicon : official journal of the International Society on Toxinology}, volume = {56}, number = {6}, pages = {1079-80; author reply 1081}, doi = {10.1016/j.toxicon.2010.06.024}, pmid = {20620159}, issn = {1879-3150}, mesh = {Animals ; Antivenins/*biosynthesis ; Camelus/*immunology ; Dose-Response Relationship, Immunologic ; Elapid Venoms/immunology ; Elapidae/physiology ; Enzyme-Linked Immunosorbent Assay ; Immunization/*methods ; Immunoglobulin G/*biosynthesis/immunology ; Neutralization Tests ; Snake Venoms/*immunology ; Time Factors ; }, } @article {pmid20614576, year = {2010}, author = {Sobas, F and Benattar, N and Bellisario, A and Marin, S and Nougier, C and Lienhart, A and Négrier, C}, title = {Impact of quality control matrix effect: application to the calculation of uncertainty of measurement in one-stage clotting factor VIII assay.}, journal = {Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis}, volume = {21}, number = {5}, pages = {498-501}, doi = {10.1097/mbc.0b013e328338dbd3}, pmid = {20614576}, issn = {1473-5733}, mesh = {Animals ; *Biological Assay ; Blood Coagulation Tests ; Endothelial Cells/cytology ; Factor VIII/*metabolism ; Hemophilia A/blood/genetics ; Mice ; Quality Control ; *Uncertainty ; }, abstract = {In Europe, the ISO 15 189 standard requires uncertainty of measurement to be calculated for all measurands. We calculated the analytical imprecision and bias of our factor VIII coagulometric assay method between 5 and 80 U/dl, using plasmas expected to be at 5, 30 and 80 U/dl of factor VIII. We implemented Meijer et al.'s [Clin Chem 2002; 48:1011-1015] long-term coefficient of variance, bias and also uncertainty of measurement calculations. Assessments used reference plasma diluted in severe haemophilic plasma, in immunodepleted factor VIII-deficient plasma and in bovine serum albumin. With plasmas diluted in severe haemophilic and immunodepleted factor VIII-deficient plasma, calculated uncertainty of measurement was 10% compared with 15% (i.e., 50% greater) for plasma diluted in albumin buffer or as calculated from European Concerted Action on Thrombosis consensus values. It is thus important to approximate the patient sample matrix to obtain as precise an estimation as possible of assay method uncertainty of measurement.}, } @article {pmid20605013, year = {2011}, author = {Proffitt, DR and Zadra, JR}, title = {Explicit and motoric dependent measures of geographical slant are dissociable: a reassessment of the findings of Durgin, Hajnal, Li, Tonge, and Stigliani (2010).}, journal = {Acta psychologica}, volume = {138}, number = {2}, pages = {285-288}, doi = {10.1016/j.actpsy.2010.06.003}, pmid = {20605013}, issn = {1873-6297}, mesh = {Hand ; Humans ; Orientation/*physiology ; Proprioception/*physiology ; Space Perception/*physiology ; }, abstract = {Durgin et al. (2010) argued that the apparent accuracy of the palmboard measure of geographical slant is accidental and reflects limitations in wrist flexion that reduce palmboard adjustments by just the right amount given the perceptual overestimations upon which they are based. This account is inconsistent with findings that verbal reports and palmboard adjustments are dissociable. In addition to previous evidence found for such dissociation, Durgin et al. also found verbal/palmboard dissociations in Experiment 2. Experiments 1 and 3 of Durgin et al. lacked verbal reports and instead compared palmboard adjustments to free-hand estimates in the context of small wooden surfaces. These experiments are not relevant to the issue of verbal/palmboard dissociability. Across studies, the accuracy of Durgin et al.'s palmboard implementation is far less than that found by others (Feresin & Agostini, 2007). The design of Durgin et al.'s Experiment 5 misrepresented the experimental conditions of Creem and Proffitt (1998), and consequently, the findings of this study have no bearing on the issue at hand.}, } @article {pmid22918072, year = {2010}, author = {Verma, SK and Srivastava, R and Kant, S and Prasad, R and Garg, R and Ahmad, I and Husain, N}, title = {A study to evaluate asbestos fiber burden in lung and pleural malignancies.}, journal = {Indian journal of medical sciences}, volume = {64}, number = {7}, pages = {315-319}, pmid = {22918072}, issn = {1998-3654}, mesh = {Adenocarcinoma/*chemistry/pathology ; Adult ; Aged ; Aged, 80 and over ; Asbestos/*analysis ; Carcinoma, Squamous Cell/*chemistry/pathology ; Female ; Humans ; Lung Neoplasms/*chemistry/pathology ; Male ; Middle Aged ; Pleural Neoplasms/*chemistry/pathology ; Small Cell Lung Carcinoma/*chemistry/pathology ; }, abstract = {BACKGROUND: There is scarcity of data on asbestos fiber burden in lung and pleural malignancies.

AIM: To evaluate asbestos fiber burden in biopsy samples of suspected lung and pleural malignancies.

STUDY DESIGN: This was a single-centre, observational study.

STUDY PERIOD: From August 2010 to July 2010.

SETTING: Department of Pulmonary Medicine, CSMMU, UP, Lucknow, a tertiary care hospital in India.

STUDY POPULATION: Suspected cases of lung and pleural malignancy.

MATERIALS AND METHODS: Biopsy tissues taken by computed tomography (CT)-guided biopsy, bronchoscopic biopsy, and pleural biopsy by Cope's needle were analyzed for histopathology and asbestos burden by Haq et al.'s method.

RESULTS: 20 patients were studied. Mean fiber burden was 9.25 × 10 4 fibers/g. Average burden in lung malignancies (11 patients) was 9.178 × 10 4 fibers/g and in pleural tissue (9 patients) was 9.332 × 10 4fibers/g. Among the different cell types, mean fiber burden in squamous cell carcinoma was 8.99 × 10 4 fibers/g, in adenocarcinoma was 9.71 × 10 4 fibers/g, and in small cell carcinoma was 7.54 × 10 4 fibers/g. Mean fiber burden in bronchoscopic endobronchial biopsy tissue was 10.69 × 10 4 fibers/g, while in CT-guided biopsy was 8.60× 10 4fibers/g.

CONCLUSION: Maximum number of fibers was found in adenocarcinoma.}, } @article {pmid20584810, year = {2010}, author = {Ross, JS}, title = {Measuring circulating miRNAs: the new "PSA" for Breast Cancer?.}, journal = {The oncologist}, volume = {15}, number = {7}, pages = {656}, pmid = {20584810}, issn = {1549-490X}, mesh = {Biomarkers, Tumor/*blood ; Breast Neoplasms/*blood ; Female ; Humans ; MicroRNAs/*blood ; }, abstract = {The article comments on Heneghan et al.'s analysis of the use of microRNAs as diagnostic tools in breast cancer.}, } @article {pmid20584395, year = {2010}, author = {Zachar, P}, title = {The abandonment of latent variables: philosophical considerations.}, journal = {The Behavioral and brain sciences}, volume = {33}, number = {2-3}, pages = {177-178}, doi = {10.1017/S0140525X10000841}, pmid = {20584395}, issn = {1469-1825}, mesh = {Humans ; Mental Disorders/*classification/*diagnosis ; Philosophy ; }, abstract = {Cramer et al.'s critique of latent variables implicitly advocates a type of scientific anti-realism which can be extended to many dispositional constructs in scientific psychology. However, generalizing Cramer et al.'s network model in this way raises concerns about its applicability to psychopathology. The model could be improved by articulating why a given cluster of symptoms should be considered disordered.}, } @article {pmid20584394, year = {2010}, author = {Yordanova, J and Kolev, V and Kirov, R and Rothenberger, A}, title = {Comorbidity in the context of neural network properties.}, journal = {The Behavioral and brain sciences}, volume = {33}, number = {2-3}, pages = {176-177}, doi = {10.1017/S0140525X1000083X}, pmid = {20584394}, issn = {1469-1825}, mesh = {Brain/*physiopathology ; Humans ; Mental Disorders/*physiopathology ; Nerve Net/*physiopathology ; }, abstract = {Cramer et al.'s network approach reconceptualizes mental comorbidity on the basis of symptom space originating from psychometric signatures. We argue that the advantages of this approach need to be regarded in the context of the multi-level functional organization of the neural substrate, ranging from neurogenetic to psychometric. Neuroelectric oscillations are proposed as a level-integrating principle.}, } @article {pmid20584392, year = {2010}, author = {van Geert, PL and Steenbeek, HW}, title = {Networks as complex dynamic systems: applications to clinical and developmental psychology and psychopathology.}, journal = {The Behavioral and brain sciences}, volume = {33}, number = {2-3}, pages = {174-175}, doi = {10.1017/S0140525X10000828}, pmid = {20584392}, issn = {1469-1825}, mesh = {Comorbidity ; Humans ; Mental Disorders/*diagnosis/*epidemiology ; Psychology/*methods ; Psychopathology/*methods ; }, abstract = {Cramer et al.'s article is an example of the fruitful application of complex dynamic systems theory. We extend their approach with examples from our own work on development and developmental psychopathology and address three issues: (1) the level of aggregation of the network, (2) the required research methodology, and (3) the clinical and educational application of dynamic network thinking.}, } @article {pmid20584379, year = {2010}, author = {Humphry, SM and McGrane, JA}, title = {Is there a contradiction between the network and latent variable perspectives?.}, journal = {The Behavioral and brain sciences}, volume = {33}, number = {2-3}, pages = {160-161}, doi = {10.1017/S0140525X10000786}, pmid = {20584379}, issn = {1469-1825}, mesh = {Humans ; Mental Disorders/*diagnosis ; Models, Psychological ; Psychometrics ; }, abstract = {First, we question whether Cramer et al.'s proposed network model can provide a viable scientific foundation for investigating comorbidity without invoking latent variables in some form. Second, the authors' claim that the network perspective is radically different from a latent variable perspective rests upon an undemonstrated premise. Without being demonstrated, we think the premise is potentially misleading.}, } @article {pmid20584378, year = {2010}, author = {Hood, SB and Lovett, BJ}, title = {Network models of psychopathology and comorbidity: philosophical and pragmatic considerations.}, journal = {The Behavioral and brain sciences}, volume = {33}, number = {2-3}, pages = {159-160}, doi = {10.1017/S0140525X10000610}, pmid = {20584378}, issn = {1469-1825}, mesh = {Humans ; Mental Disorders/classification/*diagnosis ; Philosophy ; }, abstract = {Cramer et al.'s account of comorbidity comes with a substantive philosophical view concerning the nature of psychological disorders. Although the network account is responsive to problems with extant approaches, it faces several practical and conceptual challenges of its own, especially in cases where the individual differences in network structures require the analysis of intra-individual time-series data.}, } @article {pmid20584373, year = {2010}, author = {Danks, D and Fancsali, S and Glymour, C and Scheines, R}, title = {Comorbid science?.}, journal = {The Behavioral and brain sciences}, volume = {33}, number = {2-3}, pages = {153-155}, doi = {10.1017/S0140525X10000609}, pmid = {20584373}, issn = {1469-1825}, mesh = {Algorithms ; Humans ; Mental Disorders/classification/*diagnosis ; *Models, Psychological ; }, abstract = {We agree with Cramer et al.'s goal of the discovery of causal relationships, but we argue that the authors' characterization of latent variable models (as deployed for such purposes) overlooks a wealth of extant possibilities. We provide a preliminary analysis of their data, using existing algorithms for causal inference and for the specification of latent variable models.}, } @article {pmid20584372, year = {2010}, author = {Cervone, D}, title = {Aligning psychological assessment with psychological science.}, journal = {The Behavioral and brain sciences}, volume = {33}, number = {2-3}, pages = {152-153}, doi = {10.1017/S0140525X10000737}, pmid = {20584372}, issn = {1469-1825}, mesh = {Humans ; Interview, Psychological ; Mental Disorders/classification/*diagnosis/etiology ; Self-Assessment ; }, abstract = {Network analysis is a promising step forward in efforts to align psychological assessment with explanatory theory in psychological science. The implications of Cramer et al.'s analysis are quite general. Networks analysis may illuminate functional relations not only among observable behaviors that comprise psychological disorders, but among cognitive and affective processes that causally contribute to everyday experience and action.}, } @article {pmid20580826, year = {2010}, author = {Wong, WS and Fielding, R}, title = {Prevalence of chronic fatigue among Chinese adults in Hong Kong: a population-based study.}, journal = {Journal of affective disorders}, volume = {127}, number = {1-3}, pages = {248-256}, doi = {10.1016/j.jad.2010.04.029}, pmid = {20580826}, issn = {1573-2517}, mesh = {Adolescent ; Adult ; Asian People/*psychology/*statistics & numerical data ; *Cross-Cultural Comparison ; Cross-Sectional Studies ; Fatigue Syndrome, Chronic/*epidemiology/*ethnology ; Female ; Hong Kong ; Humans ; Interview, Psychological ; Interviews as Topic ; Male ; Middle Aged ; Population Surveillance ; Quality of Life/psychology ; Risk Factors ; Socioeconomic Factors ; Young Adult ; }, abstract = {BACKGROUND: Epidemiologic data is available on chronic fatigue for Western, but not for Chinese populations. The aims of the present study were to determine the prevalence of chronic fatigue in the general population of Hong Kong, compare health and lifestyle characteristics of non-chronic fatigue and chronic fatigue cases, and identify risk factors for chronic fatigue.

METHODS: We performed telephone interviews on 5001 randomly selected Chinese adults aged ≥18 years administering the Chinese version of Chronic Fatigue Scale (ChCFS), the Hospital Anxiety and Depression Scale (HADS), and quality of life (QoL) indexed by Medical Outcomes Study 12-item Short-Form Health Survey (SF12). Lifestyle, and sociodemographic data were also collected. Chronic fatigue was defined according to Fukuda et al.'s (1994) criteria and case criterion was a ChCFS total scores ≥4.

RESULTS: The weighted prevalence of chronic fatigue was 10.7%, which was equivalent to 0.6 million adults in Hong Kong. Higher prevalence rates were found in females, older age groups, and low socioeconomic status. Fully adjusted stepwise regression analyses identified older age, retirees, housewife, existing long-term health problems, higher HADS scores, poor QoL, and low self-perceived health to be significantly associated with increased risk of chronic fatigue, whereas regular exercise was associated with decreased risk of chronic fatigue (all p<0.05).

LIMITATIONS: The cross-sectional design did not allow determination of the time course and causal relationship between chronic fatigue and associated factors.

CONCLUSIONS: Our data evidenced that chronic fatigue is common in the general population of Hong Kong, and the prevalence increased with age and was higher in the women and lower socioeconomic population.}, } @article {pmid20579840, year = {2010}, author = {Berendes, D and Keefe, FJ and Somers, TJ and Kothadia, SM and Porter, LS and Cheavens, JS}, title = {Hope in the context of lung cancer: relationships of hope to symptoms and psychological distress.}, journal = {Journal of pain and symptom management}, volume = {40}, number = {2}, pages = {174-182}, pmid = {20579840}, issn = {1873-6513}, support = {R01 CA091947/CA/NCI NIH HHS/United States ; R01 CA91947/CA/NCI NIH HHS/United States ; }, mesh = {Adaptation, Psychological ; Aged ; Analysis of Variance ; Carcinoma, Bronchogenic/complications/*psychology ; Cross-Sectional Studies ; Depression/psychology ; Emotions ; Fatigue/etiology/*psychology ; Female ; Humans ; Lung Neoplasms/complications/*psychology ; Male ; Middle Aged ; Pain/etiology/*psychology ; Stress, Psychological/*psychology ; }, abstract = {CONTEXT: Hope may be important in explaining the variability in how patients adjust to lung cancer.

OBJECTIVES: The aim of this study was to examine how hope, as conceptualized by Snyder et al., is associated with multiple indices of adjustment to lung cancer. This theoretical model of hope suggests that people with high levels of hope are able to think about the pathways to goals (pathways) and feel confident that they can pursue those pathways to reach their goals (agency).

METHODS: We hypothesized that higher levels of hope, as measured by Snyder et al.'s hope scale, would be related to lower levels of pain and other lung cancer symptoms (i.e., fatigue and cough) and lower psychological distress (i.e., depression). Participants in this study included patients with a diagnosis of lung cancer (n=51). All participants provided demographic and medical information and completed measures of hope, lung cancer symptoms, and psychological distress.

RESULTS: Data analyses found that hope was inversely associated with major symptoms of cancer (i.e., pain, fatigue, and cough) and psychological distress (i.e., depression), even after accounting for important demographic and medical variables (i.e., age and cancer stage).

CONCLUSION: The findings of this cross-sectional study highlight the potential importance of hope in understanding adjustment to lung cancer. Future longitudinal research could help reveal how hope and adjustment interact over the course of cancer survivorship.}, } @article {pmid20573745, year = {2010}, author = {Morimura, T}, title = {STEM image simulation by Bloch-wave method with layer-by-layer representation.}, journal = {Journal of electron microscopy}, volume = {59 Suppl 1}, number = {}, pages = {S23-8}, doi = {10.1093/jmicro/dfq028}, pmid = {20573745}, issn = {1477-9986}, abstract = {In a Bloch-wave-based STEM image simulation, a framework for calculating the cross section for any incoherent scattering process was formulated by Allen et al. [(2003) Lattice-resolution contrast from a focused coherent electron probe. Part I. Ultramicroscopy 96: 47-63; Part II. ibid. 96: 65-81]. They simulated the high-angle annular dark-field, back-scattered electron, electron energy-loss spectroscopy and energy-dispersive X-ray (EDX) STEM images from the inelastic scattering coefficients. Furthermore, a skilful approach for deriving the excitation amplitude and block diagonalization in the eigenvalue equation was employed to reduce computing time and memory. In the present work, I extended their scheme to a layer-by-layer representation for application to inhomogeneous crystals. Calculations for a multi-layer Si sample including a displaced layer were performed by multiplying Allen et al.'s block-diagonalized matrices. Electron intensities within the sample and EDX STEM images were calculated at various conditions. From the calculations, three-dimensional STEM analysis was considered.}, } @article {pmid20571143, year = {2011}, author = {Horder, J and Matthews, P and Waldmann, R}, title = {Placebo, prozac and PLoS: significant lessons for psychopharmacology.}, journal = {Journal of psychopharmacology (Oxford, England)}, volume = {25}, number = {10}, pages = {1277-1288}, doi = {10.1177/0269881110372544}, pmid = {20571143}, issn = {1461-7285}, mesh = {Antidepressive Agents, Second-Generation/*therapeutic use ; Controlled Clinical Trials as Topic ; Depression/*drug therapy ; Fluoxetine/*therapeutic use ; Humans ; Placebos ; Psychiatric Status Rating Scales ; }, abstract = {Kirsch et al. (2008, Initial severity and antidepressant benefits: a meta-analysis of data submitted to the Food and Drug Administration. PLoS Med 5: e45), conducted a meta-analysis of data from 35 placebo controlled trials of four newer antidepressants. They concluded that while these drugs are statistically significantly superior to placebo in acute depression, the benefits are unlikely to be clinically significant. This paper has attracted much attention and debate in both academic journals and the popular media. In this critique, we argue that Kirsch et al.'s is a flawed analysis which relies upon unusual statistical techniques biased against antidepressants. We present results showing that re-analysing the same data using more appropriate methods leads to substantially different conclusions. However, we also believe that psychopharmacology has lessons to learn from the Kirsch et al. paper. We discuss issues surrounding the interpretation of clinical trials of antidepressants, including the difficulties of extrapolating from randomized controlled trials to the clinic, and the question of failed trials. We call for more research to establish the effectiveness of antidepressants in clinically relevant populations under naturalistic conditions, for example, in relapse prevention, in patients with co-morbidities, and in primary care settings.}, } @article {pmid20563715, year = {2010}, author = {Lee, YL and Bingham, GP}, title = {Large perspective changes yield perception of metric shape that allows accurate feedforward reaches-to-grasp and it persists after the optic flow has stopped!.}, journal = {Experimental brain research}, volume = {204}, number = {4}, pages = {559-573}, pmid = {20563715}, issn = {1432-1106}, mesh = {Adolescent ; Adult ; Female ; Form Perception/*physiology ; *Hand Strength ; Humans ; Judgment ; Male ; Size Perception/*physiology ; Visual Perception/*physiology ; Young Adult ; }, abstract = {Lee et al. (Percept Psychophys 70:1032-1046, 2008a) investigated whether visual perception of metric shape could be calibrated when used to guide feedforward reaches-to-grasp. It could not. Seated participants viewed target objects (elliptical cylinders) in normal lighting using stereo vision and free head movements that allowed small (approximately 10 degrees) perspective changes. The authors concluded that poor perception of metric shape was the reason reaches-to-grasp should be visually guided online. However, Bingham and Lind (Percept Psychophys 70:524-540, 2008) showed that large perspective changes (> or =45 degrees) yield good perception of metric shape. So, now we repeated the Lee et al.'s study with the addition of information from large perspective changes. The results were accurate feedforward reaches-to-grasp reflecting accurate perception of both metric shape and metric size. Large perspective changes occur when one locomotes into a workspace in which reaches-to-grasp are subsequently performed. Does the resulting perception of metric shape persist after the large perspective changes have ceased? Experiments 2 and 3 tested reaches-to-grasp with delays (Exp. 2, 5-s delay; Exp. 3, approximately 16-s delay) and multiple objects to be grasped after a single viewing. Perception of metric shape and metric size persisted yielding accurate reaches-to-grasp. We advocate the study of nested actions using a dynamic approach to perception/action.}, } @article {pmid20562410, year = {2010}, author = {Lykins, AD and Cantor, JM and Kuban, ME and Blak, T and Dickey, R and Klassen, PE and Blanchard, R}, title = {Sexual arousal to female children in gynephilic men.}, journal = {Sexual abuse : a journal of research and treatment}, volume = {22}, number = {3}, pages = {279-289}, doi = {10.1177/1079063210372141}, pmid = {20562410}, issn = {1573-286X}, mesh = {Adult ; Arousal/physiology ; Audiovisual Aids ; Child ; Child Abuse, Sexual/classification/*diagnosis ; Female ; Humans ; Male ; *Men/psychology ; Middle Aged ; Ontario ; Pedophilia/classification/*diagnosis ; Penile Erection/*physiology ; Penis/physiology ; Plethysmography/*methods ; Psychometrics ; Regression Analysis ; Sex Offenses ; Tape Recording ; Young Adult ; }, abstract = {Phallometric assessments of single-victim sexual offenders against children have suggested that only about 50% of these men are more attracted to children than they are to adults. This has raised the question of what motivates the other 50% of men to approach young girls for sex. Freund et al. showed that gynephilic men (i.e., men preferentially attracted to adult women) evidenced greater arousal to images of prepubescent girls than to images of males of any age or to nonerotic images, arguing that gynephilic men may approach prepubescent girls as a "surrogate" for their preferred erotic targets (i.e., adult women). One might argue that these phallometric results are artifactual, given that they were obtained in a time period during which images of nudity were far less common than they are today (thus any female nudity might have elicited arousal). To address this issue, the authors examined the sexual arousal patterns of 214 contemporary men who, based on self-report, offense history, and phallometric responses, were purely gynephilic. Results showed the "classical control profile": the greatest arousal to adult women, systematically decreasing arousal as the female stimuli became younger, and essentially no arousal to any age categories of males or to neutral (nonerotic) stimuli. Arousal to both pubescent and prepubescent girls was significantly greater than to neutral stimuli (p < .001 for both). Thus, Freund et al.'s results still appear to be valid, and the explanation for child molesting that they suggest still seems to be feasible.}, } @article {pmid20558501, year = {2010}, author = {Albertyn, C and O'Dowd, S and McHugh, J and Murphy, R}, title = {Compliance with McDonald criteria and red flag recognition in a general neurology practice in Ireland.}, journal = {Multiple sclerosis (Houndmills, Basingstoke, England)}, volume = {16}, number = {6}, pages = {678-684}, doi = {10.1177/1352458510368688}, pmid = {20558501}, issn = {1477-0970}, mesh = {Adult ; Diagnosis, Differential ; Female ; Humans ; Ireland ; Male ; Multiple Sclerosis/*diagnosis ; Neurology/*standards ; Retrospective Studies ; }, abstract = {BACKGROUND: The revised McDonald criteria aim to simplify and speed the diagnosis of multiple sclerosis (MS). An important principle of the criteria holds there should be no better explanation for the clinical presentation. In Miller et al.'s consensus statement on the differential diagnosis of MS, red flags are identified that may suggest a non-MS diagnosis.

OBJECTIVE: All new patients with a practice diagnosis of MS were assessed for compliance with McDonald criteria. The group of patients not fulfilling criteria was followed up to assess compliance over time. At the end of the follow-up period, red flags were sought in the group of patients who remained McDonald criteria negative.

METHODS: Clinical notes and paraclinical tests were examined retrospectively for compliance with McDonald criteria and for the presence of red flags.

RESULTS: Sixty-two patients were identified, with two lost to follow-up. Twenty-six (42%) patients fulfilled criteria at diagnosis. After 53 months follow-up, 47 (78%) patients fulfilled criteria. In the 13 (22%) patients who remain McDonald criteria negative, a total of 20 red flags were identified, ranging from one to six per patient. Alternative diagnoses were considered and further investigations performed in 10 patients with no significantly abnormal results.

CONCLUSION: Twenty-two percent of patients still do not fulfill McDonald criteria after 53 months. Dissemination in time was not proven in the majority of patients and the lack of follow-up neuroimaging was an important factor in this. Red flags may be useful in identifying alternative diagnoses, but the yield was low in our cohort.}, } @article {pmid20550738, year = {2010}, author = {Bennis, WM and Medin, DL}, title = {Weirdness is in the eye of the beholder.}, journal = {The Behavioral and brain sciences}, volume = {33}, number = {2-3}, pages = {85-86}, doi = {10.1017/S0140525X1000004X}, pmid = {20550738}, issn = {1469-1825}, mesh = {*Cross-Cultural Comparison ; Humans ; Population Groups ; *Research Design ; }, abstract = {Henrich et al.'s critical review demonstrating that psychology research is over-reliant on WEIRD samples is an important contribution to the field. Their stronger claim that "WEIRD subjects are particularly unusual" is less convincing, however. We argue that WEIRD people's apparent distinct weirdness is a methodological side-effect of psychology's over-reliance on WEIRD populations for developing its methods and theoretical constructs.}, } @article {pmid20550731, year = {2010}, author = {Danks, D and Rose, D}, title = {Diversity in representations; uniformity in learning.}, journal = {The Behavioral and brain sciences}, volume = {33}, number = {2-3}, pages = {90-91}, doi = {10.1017/S0140525X10000075}, pmid = {20550731}, issn = {1469-1825}, mesh = {*Concept Formation ; *Cross-Cultural Comparison ; Humans ; *Learning ; Models, Psychological ; Population Groups ; }, abstract = {Henrich et al.'s conclusion that psychologists ought not assume uniformity of psychological phenomena depends on their descriptive claim that there is no pattern to the great diversity in psychological phenomena. We argue that there is a pattern: uniformity of learning processes (broadly construed), and diversity of (some) mental contents (broadly construed).}, } @article {pmid20546667, year = {2010}, author = {Gaertner, L and Sedikides, C and Cai, H and Brown, JD}, title = {It's not WEIRD, it's WRONG: when researchers overlook uNderlying genotypes, they will not detect universal processes.}, journal = {The Behavioral and brain sciences}, volume = {33}, number = {2-3}, pages = {93-94}, doi = {10.1017/S0140525X10000105}, pmid = {20546667}, issn = {1469-1825}, mesh = {*Cross-Cultural Comparison ; Culture ; *Genotype ; Humans ; Self Concept ; }, abstract = {We dispute Henrich et al.'s analysis of cultural differences at the level of a narrow behavioral-expression for assessing a universalist argument. When Researchers Overlook uNderlying Genotypes (WRONG), they fail to detect universal processes that generate observed differences in expression. We reify this position with our own cross-cultural research on self-enhancement and self-esteem.}, } @article {pmid20537871, year = {2010}, author = {Saikia, JP and Paul, S and Konwar, BK and Samdarshi, SK}, title = {Ultrasonication: enhances the antioxidant activity of metal oxide nanoparticles.}, journal = {Colloids and surfaces. B, Biointerfaces}, volume = {79}, number = {2}, pages = {521-523}, doi = {10.1016/j.colsurfb.2010.04.022}, pmid = {20537871}, issn = {1873-4367}, mesh = {Antioxidants/*metabolism ; Biphenyl Compounds/chemistry ; Ferric Compounds/*chemistry ; Free Radical Scavengers/chemistry ; Metal Nanoparticles/*chemistry/ultrastructure ; Nickel/*chemistry ; Picrates/chemistry ; Sonication/*methods ; X-Ray Diffraction ; }, abstract = {The present work is a modification for Serpen et al.'s method for antioxidant activity determination for insoluble materials with special reference to metal oxide nanoparticles. As reported in our former publications the mixing procedures were followed as mentioned by Serpen et al. A new mixing procedure was followed for enhancing the reaction between metal oxide nanoparticles and DPPH in the solution. The sonication inside a water bath enhances the DPPH scavenging capacity of metal oxide nanoparticles up to 13.94% and 18.96% in case of ferric oxide and nickel oxide nanoparticles respectively. The control DPPH solution without any nanoparticles does not show any degradation due to sonication.}, } @article {pmid21877369, year = {2010}, author = {De Bont, R}, title = {Schizophrenia, evolution and the borders of biology: on Huxley et al.'s 1964 paper in Nature.}, journal = {History of psychiatry}, volume = {21}, number = {82 Pt 2}, pages = {144-159}, doi = {10.1177/0957154x10363962}, pmid = {21877369}, issn = {0957-154X}, mesh = {*Biological Evolution ; Biological Psychiatry/*history ; Canada ; England ; Eugenics/*history ; Germany ; History, 19th Century ; History, 20th Century ; History, 21st Century ; Humans ; Periodicals as Topic/*history ; *Psychoanalytic Theory ; Publishing/*history ; Schizophrenia/*history ; }, abstract = {In October 1964, Julian Huxley, Ernst Mayr, Humphrey Osmond and Abram Hoffer co-published a controversial paper in Nature, in which they tried to explain the persistence of schizophrenia from an evolutionary perspective. This article will elucidate how the reputed authors composed this paper to make it a strong argument for biological psychiatry. Through a close reading of their correspondence, it will furthermore clarify the elements which remained unspoken in the paper, but which were elementary in its genesis. The first was the dominance of psychoanalytical theory in (American) psychiatry--a dominance which the authors wanted to break. The second was the ongoing discussion on the boundaries of biological determinism and the desirability of a new kind of eugenics. As such, the Huxley et al. paper can be used to study the central issues of psychiatry in a pivotal era of its history.}, } @article {pmid20504203, year = {2009}, author = {Arbesú, I and Soria, JM}, title = {Update to Soria et al.'s "F7 gene and clotting factor VII levels" (2005): genetic determinants of quantitative traits in thrombotic disease.}, journal = {Human biology}, volume = {81}, number = {5-6}, pages = {869-874}, doi = {10.3378/027.081.0628}, pmid = {20504203}, issn = {1534-6617}, mesh = {Blood Coagulation/*genetics ; Factor VII/*genetics ; Humans ; Quantitative Trait Loci/*genetics ; }, } @article {pmid20504201, year = {2009}, author = {Blangero, J}, title = {Update to Blangero et al.'s "Quantitative trait nucleotide analysis using Bayesian model selection" (2005): from QTL localization to functional variant identification.}, journal = {Human biology}, volume = {81}, number = {5-6}, pages = {849-852}, doi = {10.3378/027.081.0626}, pmid = {20504201}, issn = {1534-6617}, mesh = {*Bayes Theorem ; Humans ; Polymorphism, Genetic/*genetics ; *Quantitative Trait Loci ; }, } @article {pmid20504199, year = {2009}, author = {Hawks, J}, title = {Update to Eller et al.'s "Local extinction and recolonization, species effective population size, and modem human origins" (2004).}, journal = {Human biology}, volume = {81}, number = {5-6}, pages = {825-828}, doi = {10.3378/027.081.0624}, pmid = {20504199}, issn = {1534-6617}, mesh = {Animals ; *Anthropology, Physical ; *Biological Evolution ; *Extinction, Biological ; *Gene Frequency ; *Genetic Variation ; Genetics, Population/*history ; *Hominidae ; Humans ; *Population Density ; }, } @article {pmid20504188, year = {2009}, author = {Chikhi, L}, title = {Update to Chikhi et al.'s "Clinal variation in the nuclear DNA of Europeans" (1998): genetic data and storytelling--from archaeogenetics to astrologenetics?.}, journal = {Human biology}, volume = {81}, number = {5-6}, pages = {639-643}, doi = {10.3378/027.081.0612}, pmid = {20504188}, issn = {1534-6617}, mesh = {DNA/*genetics ; *Gene Frequency ; *Genetic Variation ; Genetics, Population/*history ; *Genomic Structural Variation ; Humans ; }, } @article {pmid20491742, year = {2010}, author = {Kim, SU and Seo, YS and Cheong, JY and Kim, MY and Kim, JK and Um, SH and Cho, SW and Paik, SK and Lee, KS and Han, KH and Ahn, SH}, title = {Factors that affect the diagnostic accuracy of liver fibrosis measurement by Fibroscan in patients with chronic hepatitis B.}, journal = {Alimentary pharmacology & therapeutics}, volume = {32}, number = {3}, pages = {498-505}, doi = {10.1111/j.1365-2036.2010.04353.x}, pmid = {20491742}, issn = {1365-2036}, mesh = {Adult ; Biopsy ; Elasticity Imaging Techniques ; Female ; Hepatitis B, Chronic/*diagnostic imaging ; Hepatitis C, Chronic/*diagnostic imaging ; Humans ; Liver Cirrhosis/diagnosis/*diagnostic imaging ; Male ; Middle Aged ; Sensitivity and Specificity ; }, abstract = {BACKGROUND: Interquartile range/median value (IQR/M) of liver stiffness measurement (LSM) is a factor in chronic hepatitis C (CHC) leading to over estimation of fibrosis by Fibroscan.

AIM: To investigate factors that affect the accuracy of LSM in chronic hepatitis B (CHB).

METHODS: One hundred and ninety-nine patients were enrolled. Only procedures yielding > or =10 valid measurements were considered reliable. Liver fibrosis was evaluated using the Batts and Ludwig system. Liver biopsy (LB) specimens <15 mm were considered ineligible.

RESULTS: The mean age (142 men and 57 women) was 40.1 years. A significant discordance (discordance of at least two stages between LB and LSM) was identified in 38 (19.1%) and 47 (23.6%) patients respectively, according to Marcellin et al. and Chan et al.'s cutoff values. In multivariate analyses, BMI and fibrosis stage (F0-2 vs. F3-4) were identified as independent predictors for significant discordance (P = 0.040; hazard ratio [HR], 1.126; 95% confidence interval [CI], 1.005-1.261 and P = 0.036; HR, 0.450; 95% CI, 0.213-0.949 respectively) with Marcellin et al.'s cutoffs, whereas fibrosis stage was the only independent predictor (P = 0.004; HR, 0.300; 95% CI, 0.131-0.685) with Chan's cutoffs.

CONCLUSIONS: Success rate and IQR/M were not predictive factors of the accuracy for diagnosing liver fibrosis by Fibroscan in CHB. Fibrosis stage (F0-2) was the only factor to predict significant discordance between LB and LSM.}, } @article {pmid20491721, year = {2010}, author = {Banham, L and Gilbody, S}, title = {Smoking cessation in severe mental illness: what works?.}, journal = {Addiction (Abingdon, England)}, volume = {105}, number = {7}, pages = {1176-1189}, doi = {10.1111/j.1360-0443.2010.02946.x}, pmid = {20491721}, issn = {1360-0443}, support = {07/41/05/DH_/Department of Health/United Kingdom ; }, mesh = {Adult ; Behavior Therapy ; Body Weight/drug effects ; Bupropion/therapeutic use ; Dopamine Uptake Inhibitors/therapeutic use ; Female ; Healthcare Disparities ; Humans ; Male ; Mental Disorders/*psychology ; Nicotine/therapeutic use ; Nicotinic Agonists/therapeutic use ; Randomized Controlled Trials as Topic ; Schizophrenic Psychology ; Smoking/psychology/*therapy ; Smoking Cessation/*methods/psychology ; Time Factors ; Tobacco Use Disorder/psychology/*therapy ; }, abstract = {AIMS: The physical health of people with severe mental illness (SMI) is poor. Smoking-related illnesses are a major contributor to excess mortality and morbidity. An up-to-date review of the evidence for smoking cessation interventions in SMI is needed to inform clinical guidelines.

METHODS: We searched bibliographic databases for relevant studies and independently extracted data. Included studies were randomized controlled trials (RCTs) of smoking cessation or reduction conducted in adult smokers with SMI. Interventions were compared to usual care or placebo. The primary outcome was smoking cessation and secondary outcomes were smoking reduction, change in weight, change in psychiatric symptoms and adverse events.

RESULTS: We included eight RCTs of pharmacological and/or psychological interventions. Most cessation interventions showed moderate positive results, some reaching statistical significance. One study compared behavioural support and nicotine replacement therapy (NRT) to usual care and showed a risk ratio (RR) of 2.74 (95% CI 1.10-6.81) for short-term smoking cessation, which was not significant at longer follow-up. We pooled five trials that effectively compared bupropion to placebo giving an RR of 2.77 (95% CI 1.48-5.16), which was comparable to Hughes et al.'s 2009 figures for general population data; RR = 1.69 (95% CI 1.53-1.85). Smoking reduction data were too heterogeneous for meta-analysis, but results were generally positive. Trials suggest few adverse events. All trials recorded psychiatric symptoms and the most significant changes favoured the intervention groups over the control groups.

CONCLUSIONS: Treating tobacco dependence is effective in patients with SMI. Treatments that work in the general population work for those with severe mental illness and appear approximately equally effective. Treating tobacco dependence in patients with stable psychiatric conditions does not worsen mental state.}, } @article {pmid20457048, year = {2010}, author = {Lohmueller, KE}, title = {Graydon et al. provide no new evidence that forensic STR loci are functional.}, journal = {Forensic science international. Genetics}, volume = {4}, number = {4}, pages = {273-274}, doi = {10.1016/j.fsigen.2009.09.006}, pmid = {20457048}, issn = {1878-0326}, mesh = {DNA Fingerprinting ; Gene Frequency ; *Genetics, Population ; Humans ; Phenotype ; Polymorphism, Genetic ; Racial Groups/*genetics ; *Tandem Repeat Sequences ; }, abstract = {Graydon et al. recently reported "there is a correspondence between STR polymorphism and physical traits, suggesting that STRs may not be just genetic 'junk', but may play a role in influencing phenotypic differences between people.". We argue that this conclusion is unwarranted in light of past and present work in human population genetics. Instead, Graydon et al.'s results can be explained solely by population history.}, } @article {pmid20455251, year = {2010}, author = {Witte, TK and Smith, AR and Joiner, TE}, title = {Reason for cautious optimism? Two studies suggesting reduced stigma against suicide.}, journal = {Journal of clinical psychology}, volume = {66}, number = {6}, pages = {611-626}, pmid = {20455251}, issn = {1097-4679}, support = {F31 MH077386/MH/NIMH NIH HHS/United States ; F31 MH083382/MH/NIMH NIH HHS/United States ; }, mesh = {Adolescent ; Arizona ; Data Collection ; Female ; Florida ; Humans ; Male ; *Stereotyping ; Students/*psychology ; Suicide/*psychology ; Universities ; Young Adult ; }, abstract = {We present data from two studies that aimed to investigate stigma against suicide. In Study 1, we employed Milgram et al.'s (1965) "lost letter" technique. We predicted that fewer letters addressed to a fictitious organization with the word "suicide" in its name would be returned than letters addressed to fictitious heart disease or diabetes organizations, presumably due to stigma. Contrary to expectation, there were no differences in the percentage of letters returned for each condition, despite power to detect small effects. In Study 2 we compared scores on the Suicide Opinion Questionnaire (SOQ; Domino, Gibson, Poling, & Westlake, 1980) from a study published in 1988 (Domino, MacGregor, & Hannah, 1988) to scores from a study conducted 19 years later. Results demonstrated reduced stigma toward suicide, with the belief that suicide is morally bad exhibiting the largest change.}, } @article {pmid20436208, year = {2010}, author = {García-Pérez, MA and Alcalá-Quintana, R}, title = {Reminder and 2AFC tasks provide similar estimates of the difference limen: a reanalysis of data from Lapid, Ulrich, and Rammsayer (2008) and a discussion of Ulrich and Vorberg (2009).}, journal = {Attention, perception & psychophysics}, volume = {72}, number = {4}, pages = {1155-1178}, doi = {10.3758/APP.72.4.1155}, pmid = {20436208}, issn = {1943-393X}, mesh = {Acoustic Stimulation/methods ; Attention ; Auditory Threshold ; *Choice Behavior ; *Differential Threshold ; *Discrimination, Psychological ; Humans ; *Judgment ; Mental Recall ; Models, Statistical ; Photic Stimulation/methods ; Psychometrics/methods/statistics & numerical data ; Psychomotor Performance ; Psychophysics/methods ; Research Design/standards ; Signal Detection, Psychological ; Task Performance and Analysis ; Time Perception ; Visual Perception ; }, abstract = {Lapid, Ulrich, and Rammsayer (2008) reported that estimates of the difference limen (DL) from a two-alternative forced choice (2AFC) task are higher than those obtained from a reminder task. This article reanalyzes their data in order to correct an error in their estimates of the DL from 2AFC data. We also extend the psychometric functions fitted to data from both tasks to incorporate an extra parameter that has been shown to allow obtaining accurate estimates of the DL that are unaffected by lapses. Contrary to Lapid et al.'s conclusion, our reanalysis shows that DLs estimated with the 2AFC task are only minimally (and not always significantly) larger than those estimated with the reminder task. We also show that their data are contaminated by response bias, and that the small remaining difference between DLs estimated with 2AFC and reminder tasks can be reasonably attributed to the differential effects that response bias has in either task as they were defined in Lapid et al.'s experiments. Finally, we discuss a novel approach presented by Ulrich and Vorberg (2009) for fitting psychometric functions to 2AFC discrimination data.}, } @article {pmid20415496, year = {2010}, author = {Ishida, Y and Kato, Y and Zhao, L and Nagamochi, H and Akutsu, T}, title = {Branch-and-bound algorithms for enumerating treelike chemical graphs with given path frequency using detachment-cut.}, journal = {Journal of chemical information and modeling}, volume = {50}, number = {5}, pages = {934-946}, doi = {10.1021/ci900447z}, pmid = {20415496}, issn = {1549-960X}, mesh = {*Algorithms ; *Computational Biology/methods ; Computing Methodologies ; Databases, Factual ; Molecular Structure ; }, abstract = {Computational methods of enumerating chemical graphs have attained great importance in chemoinformatics since they lead to a variety of useful applications including structure determination of novel chemical compounds. Recently, Fujiwara et al. have presented an efficient branch-and-bound algorithm for enumerating treelike chemical graphs with given path frequency. In this paper, we augment Fujiwara et al.'s algorithm by introducing a new bounding operation called detachment-cut to reduce further the search space in the branch-and-bound framework. Experimental results on much chemical compound data show that our proposed algorithm achieves better performance than Fujiwara et al.'s algorithm in computation time. A program that implements our algorithm can be used freely via Web server.}, } @article {pmid20388590, year = {2010}, author = {Chiha, M and Merouani, S and Hamdaoui, O and Baup, S and Gondrexon, N and Pétrier, C}, title = {Modeling of ultrasonic degradation of non-volatile organic compounds by Langmuir-type kinetics.}, journal = {Ultrasonics sonochemistry}, volume = {17}, number = {5}, pages = {773-782}, doi = {10.1016/j.ultsonch.2010.03.007}, pmid = {20388590}, issn = {1873-2828}, mesh = {Computer Simulation ; Hydrogen Peroxide/*chemistry ; Kinetics ; *Models, Chemical ; Organic Chemicals/*chemistry/*radiation effects ; Radiation Dosage ; *Sonication ; }, abstract = {Sonochemical degradation of phenol (Ph), 4-isopropylphenol (4-IPP) and Rhodamine B (RhB) in aqueous solutions was investigated for a large range of initial concentrations in order to analyze the reaction kinetics. The initial rates of substrate degradation and H(2)O(2) formation as a function of initial concentrations were determined. The obtained results show that the degradation rate increases with increasing initial substrate concentration up to a plateau and that the sonolytic destruction occurs mainly through reactions with hydroxyl radicals in the interfacial region of cavitation bubbles. The rate of H(2)O(2) formation decreases with increasing substrate concentration and reaches a minimum, followed by almost constant production rate for higher substrate concentrations. Sonolytic degradation data were analyzed by the models of Okitsu et al. [K. Okitsu, K. Iwasaki, Y. Yobiko, H. Bandow, R. Nishimura, Y. Maeda, Sonochemical degradation of azo dyes in aqueous solution: a new heterogeneous kinetics model taking into account the local concentration OH radicals and azo dyes, Ultrason. Sonochem. 12 (2005) 255-262.] and Seprone et al. [N. Serpone, R. Terzian, H. Hidaka, E. Pelizzetti, Ultrasonic induced dehalogenation and oxidation of 2-, 3-, and 4-chlorophenol in air-equilibrated aqueous media. Similarities with irradiated semiconductor particulates, J. Phys. Chem. 98 (1994) 2634-2640.] developed on the basis of a Langmuir-type mechanism. The five linearized forms of the Okitsu et al.'s equation as well as the non-linear curve fitting analysis method were discussed. Results show that it is not appropriate to use the coefficient of determination of the linear regression method for comparing the best-fitting. Among the five linear expressions of the Okitsu et al.'s kinetic model, form-2 expression very well represent the degradation data for Ph and 4-IPP. Non-linear curve fitting analysis method was found to be the more appropriate method to determine the model parameters. An excellent representation of the experimental results of sonolytic destruction of RhB was obtained using the Serpone et al.'s model. The Serpone et al.'s model gives a worse fit for the sonolytic degradation data of Ph and 4-IPP. These results indicate that Ph and 4-IPP undergo degradation predominantly at the bubble/solution interface, whereas RhB undergoes degradation at both bubble/solution interface and in the bulk solution.}, } @article {pmid20382906, year = {2010}, author = {Gould, M and Adler, A and Zamorski, M and Castro, C and Hanily, N and Steele, N and Kearney, S and Greenberg, N}, title = {Do stigma and other perceived barriers to mental health care differ across Armed Forces?.}, journal = {Journal of the Royal Society of Medicine}, volume = {103}, number = {4}, pages = {148-156}, pmid = {20382906}, issn = {1758-1095}, mesh = {Adult ; Australia ; Canada ; Female ; *Health Services Accessibility/statistics & numerical data ; Humans ; Male ; Mental Disorders/diagnosis/*psychology ; *Mental Health Services/statistics & numerical data ; Middle Aged ; Military Personnel/*psychology ; New Zealand ; Patient Acceptance of Health Care ; *Prejudice ; Psychological Tests ; Social Perception ; Surveys and Questionnaires ; United States ; Young Adult ; }, abstract = {OBJECTIVES: Military organizations are keen to address barriers to mental health care yet stigma and barriers to care remain little understood, especially potential cultural differences between Armed Forces. The aim of this study was to compare data collected by the US, UK, Australian, New Zealand and Canadian militaries using Hoge et al.'s perceived stigma and barriers to care measure (Combat duty in Iraq and Afghanistan, mental health problems and barriers to care. New Engl J Med 2004;351:13-22).

DESIGN: Each member country identified data sources that had enquired about Hoge et al.'s perceived stigma and perceived barriers to care items in the re-deployment or immediate post-deployment period. Five relevant statements were included in the study.

SETTING: US, UK Australian, New Zealand and Canadian Armed Forces.

RESULTS: Concerns about stigma and barriers to care tended to be more prominent among personnel who met criteria for a mental health problem. The pattern of reported stigma and barriers to care was similar across the Armed Forces of all five nations.

CONCLUSIONS: Barriers to care continue to be a major issue for service personnel within Western military forces. Although there are policy, procedural and cultural differences between Armed Forces, the nations studied appear to share some similarities in terms of perceived stigma and barriers to psychological care. Further research to understand patterns of reporting and subgroup differences is required.}, } @article {pmid20370112, year = {2010}, author = {Watanabe, Y and Nakano, H and Tatewaki, H}, title = {Effect of removing the no-virtual pair approximation on the correlation energy of the He isoelectronic sequence. II. Point nuclear charge model.}, journal = {The Journal of chemical physics}, volume = {132}, number = {12}, pages = {124105}, doi = {10.1063/1.3359857}, pmid = {20370112}, issn = {1089-7690}, abstract = {The correlation energies (CEs) of the He isoelectronic sequence Z=2-116 with a point nuclear charge model were investigated with the four component relativistic configuration interaction method. We obtained CEs with and without the virtual pair approximation which are close to the values from Pestka et al.'s Hylleraas-type configuration interaction calculation. We also found that the uniform charge and point charge models for the nucleus differ substantially for Z > or = 100.}, } @article {pmid24347674, year = {2010}, author = {Meyer, IH}, title = {Identity, Stress, and Resilience in Lesbians, Gay Men, and Bisexuals of Color.}, journal = {The Counseling psychologist}, volume = {38}, number = {3}, pages = {}, pmid = {24347674}, issn = {0011-0000}, support = {G13 LM007660/LM/NLM NIH HHS/United States ; R01 MH066058/MH/NIMH NIH HHS/United States ; }, abstract = {The author addresses two issues raised in Moradi, DeBlaere, and Huang's Major Contribution to this issue: the intersection of racial/ethnic and lesbian, gay, and bisexual (LGB) identities and the question of stress and resilience. The author expands on Moradi et al.'s work, hoping to encourage further research. On the intersection of identities, the author notes that LGB identities among people of color have been construed as different from the identities of White LGB persons, purportedly because of an inherent conflict between racial/ethnic and gay identities. The author suggests that contrary to this, LGB people of color can have positive racial/ethnic and LGB identities. On the question of stress and resilience, hypotheses have suggested that compared with White LGB individuals, LGB people of color have both more stress and more resilience. The author addresses the competing hypotheses within the larger perspective of minority stress theory, noting that the study of stress and resilience among LGB people of color is relevant to core questions about social stress as a cause of mental disorders.}, } @article {pmid20348568, year = {2010}, author = {Milberg, WP and McGlinchey, RE}, title = {Comment on Shomstein, Kimchi, Hammer, and Behrmann (2010): a case study in methodological anosagnosia?.}, journal = {Attention, perception & psychophysics}, volume = {72}, number = {3}, pages = {619-21; discussion 622-7}, doi = {10.3758/APP.72.3.619}, pmid = {20348568}, issn = {1943-393X}, mesh = {*Agnosia ; Attention ; Awareness ; Humans ; Perceptual Disorders ; }, abstract = {Shomstein, Kimchi, Hammer, and Behrmann (2010) try to capitalize on the apparent dissociation between vision and the processes that seem to mediate neglect patients' attentional selection and awareness to investigate the processing of perceptual grouping in the absence of visual attention. We argue that to assess this type of dissociation requires specific methodological adaptations to determine whether visual attention is in operation. We caution that Shomstein et al.'s article does not present convincing evidence of grouping without attentional selection because they do not directly assess attentional selection in their experimental task.}, } @article {pmid20345614, year = {2010}, author = {Jayaram, A and Zeevi, A and Bentlejewski, C and Lin, Y and Michaels, MG}, title = {Immune response of young children using ATP-based Cylex assay: a brief report.}, journal = {Pediatric transplantation}, volume = {14}, number = {5}, pages = {664-666}, doi = {10.1111/j.1399-3046.2010.01321.x}, pmid = {20345614}, issn = {1399-3046}, support = {UL1 RR024153/RR/NCRR NIH HHS/United States ; }, mesh = {Age Factors ; Concanavalin A/immunology/*pharmacology ; Female ; Humans ; *Immunoassay ; Infant ; Male ; Mitogens/*immunology/*pharmacology ; Phytohemagglutinins/immunology/*pharmacology ; }, abstract = {Data on immune responses of young children using ATP release-based Cylex assay are insufficient. This study measured the immune response of healthy children less than three years of age to mitogens, PHA and Con-A. Blood was obtained from children attending routine health care visits. The Cylex assay was used to measure ATP production by CD4+ and CD3+ cells in response to PHA and Con-A, respectively. Samples from 20 children less than three years (range 10-27 months) were evaluated. The mean ATP production by CD4+ lymphocytes following PHA stimulation was 376 ng/mL (95% CI 17.1-735), which was similar to the response of older children in Hooper et al.'s (Clin Transplant 2005;19:834) study (p-value 0.28). The mean and median ATP production by CD3+ cells following Con-A stimulation were 114 ng/mL and 93.3 ng/mL, respectively (95% CI for median 45.2,148.6). The data suggest that although the immune system of young infants and toddlers is evolving, they are still able to respond to mitogen stimulation similar to older children.}, } @article {pmid20230660, year = {2010}, author = {Fischer, M and Scharloo, M and Abbink, J and van 't Hul, A and van Ranst, D and Rudolphus, A and Weinman, J and Rabe, K and Kaptein, AA}, title = {The dynamics of illness perceptions: testing assumptions of Leventhal's common-sense model in a pulmonary rehabilitation setting.}, journal = {British journal of health psychology}, volume = {15}, number = {Pt 4}, pages = {887-903}, doi = {10.1348/135910710X492693}, pmid = {20230660}, issn = {1359-107X}, mesh = {*Adaptation, Psychological ; *Attitude to Health ; Disease Progression ; Female ; Humans ; Internal-External Control ; Longitudinal Studies ; Male ; Middle Aged ; *Models, Psychological ; Netherlands ; Patient Satisfaction ; Pulmonary Disease, Chronic Obstructive/*psychology/*rehabilitation ; Quality of Life ; }, abstract = {OBJECTIVES: Although Leventhal's common-sense model (CSM) is proposed to represent a dynamic system, limited research has been conducted to investigate whether and how illness perceptions change. This study tested two hypotheses from the CSM about the dynamics of illness perceptions of patients with chronic obstructive pulmonary disease (COPD) in a pulmonary rehabilitation setting.

DESIGN AND METHODS: The study employed a longitudinal design. Patients with COPD (N=87) who took part in a pulmonary rehabilitation programme filled out the Illness Perception Questionnaire - Revised (IPQ-R) before and after treatment and rated the degree to which the rehabilitation had led to the achievement of desired outcomes. Clinical variables and quality of life (Chronic Respiratory Disease Questionnaire) data were obtained from medical records.

RESULTS: In line with expectations, results showed that, at baseline, longer time since diagnosis was associated to perceptions corresponding with a chronic illness model (longer illness duration, more experienced consequences, less perceived personal controllability), after correction for clinical variables. After completion of the rehabilitation programme, patients who were more convinced that their participation had led to the achievement of desired outcomes were less concerned about the negative consequences of COPD, had stronger perceptions about the variability in symptoms (cyclical timeline) and had stronger perceptions of personal controllability Conclusions: We conclude that, in accordance with Leventhal et al.'s CSM, coping with an illness is a continuous process and the achievement of desired outcomes during treatment is likely to enable patients to adopt a more positive representation of their illness.}, } @article {pmid20229919, year = {2009}, author = {Lee, DG and Park, HJ and Heppner, MJ}, title = {Do clients' problem-solving appraisals predict career counseling outcomes or vice versa? A reanalysis of Heppner, et al.}, journal = {Psychological reports}, volume = {105}, number = {3 Pt 2}, pages = {1159-1166}, doi = {10.2466/PR0.105.F.1159-1166}, pmid = {20229919}, issn = {0033-2941}, mesh = {Adolescent ; Adult ; Aged ; Aptitude Tests/*statistics & numerical data ; Career Choice ; Decision Making ; Female ; Humans ; Male ; Middle Aged ; Midwestern United States ; Models, Statistical ; Personality Inventory/statistics & numerical data ; *Problem Solving ; Psychometrics ; *Vocational Guidance ; Young Adult ; }, abstract = {Using Heppner, et al.'s data from 2004, this study tested career counseling clients in the United States on problem-solving appraisal scores and career-related variables. A cross-lagged panel design with structural equation modeling was used. Results supported the link between clients' precounseling problem-solving appraisal scores and career outcome. This finding held for career decision-making, but not for vocational identity. The study provided further support for Heppner, et al.'s findings, highlighting the influential role of clients' problem-solving appraisals in advancing their career decision-making processes.}, } @article {pmid20229368, year = {2010}, author = {Bachner, YG and Ayalon, L}, title = {Initial examination of the psychometric properties of the short Hebrew version of the Zarit Burden Interview.}, journal = {Aging & mental health}, volume = {14}, number = {6}, pages = {725-730}, doi = {10.1080/13607861003601841}, pmid = {20229368}, issn = {1364-6915}, mesh = {Aged ; Aged, 80 and over ; Caregivers/*psychology ; *Cost of Illness ; Dementia ; Persons with Disabilities ; Factor Analysis, Statistical ; Female ; Humans ; Israel ; Male ; Middle Aged ; *Psychometrics ; *Surveys and Questionnaires ; }, abstract = {OBJECTIVES: Given the sharp increase in individuals with cognitive and physical impairments, the evaluation of burden has become common in both caregiving research and clinical practice. The Zarit Burden Interview (ZBI) is the first and one of the most commonly used measures of caregiver burden. This study examines the psychometric properties and factor structure of a Hebrew version of Bedard et al.'s [Bedard, M., Molloy, D.W., Squire, L., Dubois, S., Lever, J.A., & O'Donnell, M. (2001). The Zarit Burden Interview: A new short version and screening version. The Gerontologist, 41, 652-657] short ZBI scale (ZBI-HS).

METHODS: A total of 148 primary caregivers of individuals with cognitive and/or physical impairments completed the ZBI-HS. The factor structure of the ZBI-HS was assessed using exploratory factor analysis (EFA) and concurrent validity was examined.

RESULTS: The EFA supported the two-factor structure as reported by Bedard et al. (2001). Concurrent validity was supported by the ZBI-HS negative association with caregivers' well-being and positive association with caregivers' distress over behavioral problems of care-recipients.

CONCLUSION: These findings suggest that the short version of the ZBI-HS can be used as an effective tool for measuring caregiving burden.}, } @article {pmid20210497, year = {2010}, author = {Pluess, M and Belsky, J}, title = {Differential susceptibility to parenting and quality child care.}, journal = {Developmental psychology}, volume = {46}, number = {2}, pages = {379-390}, doi = {10.1037/a0015203}, pmid = {20210497}, issn = {1939-0599}, support = {U10-HD25420/HD/NICHD NIH HHS/United States ; }, mesh = {Achievement ; Adaptation, Psychological ; Child ; Child Behavior Disorders/*etiology ; Child Care/methods/*psychology/statistics & numerical data ; Child Development ; Child, Preschool ; *Disease Susceptibility ; Female ; Humans ; Longitudinal Studies ; Male ; *Parent-Child Relations ; Parenting/*psychology ; Regression Analysis ; Social Adjustment ; Temperament ; Time Factors ; United States ; }, abstract = {Research on differential susceptibility to rearing suggests that infants with difficult temperaments are disproportionately affected by parenting and child care quality, but a major U.S. child care study raises questions as to whether quality of care influences social adjustment. One thousand three hundred sixty-four American children from reasonably diverse backgrounds were followed from 1 month to 11 years with repeated observational assessments of parenting and child care quality, as well as teacher report and standardized assessments of children's cognitive-academic and social functioning, to determine whether those with histories of difficult temperament proved more susceptible to early rearing effects at ages 10 and 11. Evidence for such differential susceptibility emerges in the case of both parenting and child care quality and with respect to both cognitive-academic and social functioning. Differential susceptibility to parenting and child care quality extends to late middle childhood. J. Belsky, D. L. Vandell, et al.'s (2007) failure to consider such temperament-moderated rearing effects in their evaluation of long-term child care effects misestimates effects of child care quality on social adjustment.}, } @article {pmid20192555, year = {2010}, author = {Huesmann, LR}, title = {Nailing the coffin shut on doubts that violent video games stimulate aggression: comment on Anderson et al. (2010).}, journal = {Psychological bulletin}, volume = {136}, number = {2}, pages = {179-181}, pmid = {20192555}, issn = {1939-1455}, support = {R01 HD049837/HD/NICHD NIH HHS/United States ; }, mesh = {Adolescent ; Adolescent Behavior/psychology ; Aggression/*psychology ; Child ; Child Behavior/psychology ; Cross-Cultural Comparison ; Female ; Humans ; Japan ; Male ; United States ; Video Games/*psychology ; Violence/*psychology ; }, abstract = {Over the past half century the mass media, including video games, have become important socializers of children. Observational learning theory has evolved into social-cognitive information processing models that explain that what a child observes in any venue has both short-term and long-term influences on the child's behaviors and cognitions. C. A. Anderson et al.'s (2010) extensive meta-analysis of the effects of violent video games confirms what these theories predict and what prior research about other violent mass media has found: that violent video games stimulate aggression in the players in the short run and increase the risk for aggressive behaviors by the players later in life. The effects occur for males and females and for children growing up in Eastern or Western cultures. The effects are strongest for the best studies. Contrary to some critics' assertions, the meta-analysis of C. A. Anderson et al. is methodologically sound and comprehensive. Yet the results of meta-analyses are unlikely to change the critics' views or the public's perception that the issue is undecided because some studies have yielded null effects, because many people are concerned that the implications of the research threaten freedom of expression, and because many people have their identities or self-interests closely tied to violent video games.}, } @article {pmid20189305, year = {2010}, author = {Kacher, J and Basinger, J and Adams, BL and Fullwood, DT}, title = {Reply to comment by Maurice et al. in response to "Bragg's Law Diffraction Simulations for Electron Backscatter Diffraction Analysis".}, journal = {Ultramicroscopy}, volume = {110}, number = {7}, pages = {741-743}, doi = {10.1016/j.ultramic.2010.02.004}, pmid = {20189305}, issn = {1879-2723}, abstract = {A reply to Maurice et al.'s comment on "Bragg's Law Diffraction Simulations for Electron Backscatter Diffraction" is presented. A new method for microscope geometry calibration is briefly presented. Also, evidence that simple diffraction simulations can be profitable tools for absolute elastic strain measurements in crystalline materials is reiterated.}, } @article {pmid22401997, year = {2010}, author = {Sarnat, J}, title = {Key competencies of the psychodynamic psychotherapist and how to teach them in supervision.}, journal = {Psychotherapy (Chicago, Ill.)}, volume = {47}, number = {1}, pages = {20-27}, doi = {10.1037/a0018846}, pmid = {22401997}, issn = {1939-1536}, mesh = {*Clinical Competence ; Female ; Humans ; Mental Disorders/*therapy ; Professional-Patient Relations ; Psychotherapy/*education/*organization & administration ; }, abstract = {Four of Rodolfa et al.'s (2005) competencies in professional psychology-relationship, self-reflection, assessment-case conceptualization, and intervention-are key for the psychodynamic psychotherapist. Relationship lies at the heart of what is understood to be curative about psychodynamic psychotherapy. Self-reflection implies a complex and highly developed process that includes but goes beyond Rodolfa et al.'s and Kaslow, Dunn, and Smith's (2008) definitions. Competent assessment, diagnosis, and case conceptualization entails making inferences about unconscious processes by observing the client and also one's own experience, and integrating these inferences with theory. Effective psychodynamic intervention is derived from what the psychotherapist has experienced, processed, and conceptualized about the relationship with the client and about the client's internal object world. An extended vignette shows these competencies emerging in a psychotherapist-in-training, facilitated by an intense interaction with a supervisor. Although the supervisory and clinical tasks are different, the supervisor provides a relationship experience that models these same competencies for the supervisee and catalyzes their development in the supervisee.}, } @article {pmid20167377, year = {2010}, author = {Kempke, S and Goossens, L and Luyten, P and Bekaert, P and Van Houdenhove, B and Van Wambeke, P}, title = {Predictors of outcome in a multi-component treatment program for chronic fatigue syndrome.}, journal = {Journal of affective disorders}, volume = {126}, number = {1-2}, pages = {174-179}, doi = {10.1016/j.jad.2010.01.073}, pmid = {20167377}, issn = {1573-2517}, mesh = {Activities of Daily Living ; Adult ; Aged ; Cognitive Behavioral Therapy ; Depression/physiopathology/psychology ; Exercise Therapy ; Fatigue Syndrome, Chronic/physiopathology/psychology/*therapy ; Female ; Humans ; Logistic Models ; Male ; Middle Aged ; Odds Ratio ; Pain/physiopathology ; Psychiatric Status Rating Scales ; Regression Analysis ; Relaxation Therapy ; Self Efficacy ; Severity of Illness Index ; Treatment Outcome ; Young Adult ; }, abstract = {BACKGROUND: Little is known about factors predicting treatment outcome in chronic fatigue syndrome (CFS).

METHODS: Based on Vercoulen et al.'s (1998) cognitive-behavioral model of perpetuating factors in CFS, the predictive value of the following patient characteristics were examined in a sample of 178 CFS patients who followed a multi-component treatment program: (1) somatic attributions, (2) psychological attributions, (3) sense of control over symptoms, (4) physical activity, (5) functional impairment, (6) somatic focus, and (7) severity of depression.

RESULTS: Only pre-treatment severity of depression was associated with negative treatment outcome defined in terms of post-treatment fatigue and improvement in fatigue.

LIMITATIONS: The study was conducted at a tertiary care centre and did not include a control group or a long-term follow-up.

CONCLUSIONS: Level of depression may be the most important factor of the cognitive-behavioral model predicting post-treatment fatigue in CFS. Hence, findings suggest that treatment of CFS should include a focus on severity of depression.}, } @article {pmid20163755, year = {2010}, author = {Wellisch, DK and Cohen, MM}, title = {The special case of complicated grief in women at high risk for breast cancer.}, journal = {Palliative & supportive care}, volume = {8}, number = {1}, pages = {7-15}, doi = {10.1017/S1478951509990654}, pmid = {20163755}, issn = {1478-9523}, mesh = {Adult ; Anxiety Disorders/diagnosis/epidemiology/psychology ; Breast Neoplasms/*epidemiology/*genetics/psychology ; Diagnostic and Statistical Manual of Mental Disorders ; Female ; Genetic Counseling ; *Grief ; Humans ; Middle Aged ; Risk Factors ; Stress Disorders, Post-Traumatic/diagnosis/*epidemiology/*etiology ; Surveys and Questionnaires ; Young Adult ; }, abstract = {OBJECTIVE: Exploration of complicated grief focusing on the relationship of post-traumatic stress disorder (PTSD) and complicated grief in a population of women at high risk for developing breast cancer. Special reference is made to women who have experienced a material death.

METHOD: We reflected on the clinical attributes of the Revlon UCLA High Risk Clinic population in terms of their own perceived risk of developing breast cancer. For part of our population, their perceived risk was coupled with their reactions to the loss of their mothers to breast cancer. We compared and contrasted this pattern of reactions to those described by Licihtenthal et al. (2004) in their developmental review of complicated grief as a distinct disorder.

RESULTS: We concluded that our population of women differed from Lichtenthal et al.'s (2004) model for complicated grief. Lichtenthal's group postulated that the key element of complicated grief involves the protracted nature of separation anxiety and distress and excludes PTSD. In our populations, the daughter with complicated grief experiences a combination of separation anxiety and a type of PTSD involving anxiety over the perceived certainty of her own future diagnosis of breast cancer. It was noteworthy that Lichtenthal's model population was composed of individuals caring for terminally ill spouses. Significantly, the spousal caretakers did not have an ongoing genetic link to their partners whereas our population is genetically linked. We postulate that this accounts for the unique presentation of complicated grief and ptsd in our population.

SIGNIFICANCE OF RESULTS: We submit that this combination of complicated grief and PTSD requires a cognitive reframing of their perceived inevitability of developing breast cancer and desensitization techniques to help high risk women pursue preventative health care rather than avoiding it.}, } @article {pmid20161139, year = {2009}, author = {Silbert, NH and de Jong, KJ and Thomas, RD and Townsend, JT}, title = {Diagonal d' does not (always) diagnose failure of separability: An addendum to.}, journal = {Journal of phonetics}, volume = {37}, number = {3}, pages = {339-343}, pmid = {20161139}, issn = {0095-4470}, support = {R01 MH057717/MH/NIMH NIH HHS/United States ; }, abstract = {Kingston, Diehl, Kirk, and Castleman (Journal of Phonetics, 2008) present a sophisticated experimental design and detection theoretic analysis of the internal auditory structure of phonological contrasts. However, a potentially important aspect of multidimensional detection theory - the covariance structure of assumed underlying multivariate Gaussian perceptual densities - was left unexplored. We discuss Kingston, et al.'s approach in the context of a general definition of multidimensional d' and present a description of two distinct configurations of perceptual densities requiring fundamentally different interpretations that account equally well for the "mean-shift integrality" results reported by Kingston, et al. We end with a brief discussion of approaches to distinguishing these underlying configurations empirically.}, } @article {pmid20160843, year = {2009}, author = {Spillane, NS and Smith, GT}, title = {On the Pursuit of Sound Science for the Betterment of the American Indian Community: Reply to Beals et al.}, journal = {Psychological bulletin}, volume = {135}, number = {2}, pages = {344-346}, pmid = {20160843}, issn = {1939-1455}, support = {R01 AA016166/AA/NIAAA NIH HHS/United States ; R01 AA016978/AA/NIAAA NIH HHS/United States ; }, abstract = {We argue that ongoing criticism of existing theories, the development of alternative theories, and empirical theory tests offer the best chance for advancing American Indian research. We, therefore note our appreciation for Beals et al.'s comments. We nevertheless did disagree with many of Beals et al.'s specific claims, noting that (a) our characterization of the existing literature on reservation-dwelling American Indian drinking was accurate; (b) no argument made by Beals et al. undermines their theoretical contention that there is a relative lack of contingency between access to basic life reinforcers and sobriety on many reservations; (c) our theory was developed in a responsible manner: a reservation-tied American Indian developed the theory, which was reviewed by a reservation leadership team, a cultural consultant, and reviewers for this journal, at least one of whom consulted leaders of other reservations; and (d) our theory was based on previous interdisciplinary theory development. We encourage the development and testing of new, alternative theories.}, } @article {pmid20160288, year = {2010}, author = {Salmon, JP and McMullen, PA and Filliter, JH}, title = {Norms for two types of manipulability (graspability and functional usage), familiarity, and age of acquisition for 320 photographs of objects.}, journal = {Behavior research methods}, volume = {42}, number = {1}, pages = {82-95}, doi = {10.3758/BRM.42.1.82}, pmid = {20160288}, issn = {1554-3528}, mesh = {Adolescent ; Adult ; Age Factors ; Female ; *Hand Strength ; Humans ; *Learning ; Male ; *Recognition, Psychology ; Semantics ; Young Adult ; }, abstract = {There is increasing interest in the role that manipulability plays in processing objects. To date, Magnié, Besson, Poncet, and Dolisi's (2003) manipulability ratings, based on the degree to which objects can be uniquely pantomimed, have been the reference point for many studies. However, these ratings do not fully capture some relevant dimensions of manipulability, including whether an object is graspable and the extent to which functional motor associations above and beyond graspability are present. To address this, we collected ratings of these dimensions, in addition to ratings of familiarity and age of acquisition (AoA), for a set of 320 black-and-white photographs of objects. Familiarity and AoA ratings were highly correlated with previously reported ratings of the same dimensions (r = .853, p < .001, and r = .771, p < .001, respectively), validating the present norms. Grasping and functional use ratings, in contrast, were more moderately correlated with Magnié et al.'s pantomime manipulability ratings (r = .507, p < .001). These results were taken as evidence that the new manipulability ratings collected in this research capture distinct aspects of object manipulability. The complete stimuli and norms from this study may be downloaded from http://brm.psychonomic-journals.org/content/supplemental.}, } @article {pmid20156606, year = {2010}, author = {Pluskiewicz, W and Adamczyk, P and Franek, E and Leszczynski, P and Sewerynek, E and Wichrowska, H and Napiorkowska, L and Kostyk, T and Stuss, M and Stepien-Klos, W and Golba, KS and Drozdzowska, B}, title = {Ten-year probability of osteoporotic fracture in 2012 Polish women assessed by FRAX and nomogram by Nguyen et al.-Conformity between methods and their clinical utility.}, journal = {Bone}, volume = {46}, number = {6}, pages = {1661-1667}, doi = {10.1016/j.bone.2010.02.012}, pmid = {20156606}, issn = {1873-2763}, mesh = {Age Factors ; Aged ; Aged, 80 and over ; Arthritis, Rheumatoid/epidemiology/physiopathology ; Bone Density ; Female ; Femur Neck/injuries ; Fractures, Bone/*epidemiology ; Hip Fractures/epidemiology/physiopathology ; Humans ; Middle Aged ; Osteoporosis/epidemiology/physiopathology ; Osteoporosis, Postmenopausal/epidemiology ; Risk Factors ; }, abstract = {PURPOSE: The aim of the cross-sectional study was to establish the degree of conformity between 10-year probability of osteoporotic fracture, assessed by FRAX, and using the nomograms, as proposed by Nguyen at al.

METHODS: Postmenopausal Polish women (2012) were examined in their mean age of 68.5+/-7.9 years (age range 55-90 years). Fracture probability by FRAX was based on age, BMI, prior fracture, hip fracture in parents, steroid use, rheumatoid arthritis, alcohol use, secondary osteoporosis and T-score for femoral neck BMD. Fracture probability by Nguyen's nomograms was based on age, the number of prior fractures, the number of falls and T-score for femoral neck BMD.

RESULTS: The mean conformity rate was 79.1% for any fracture risk (for threshold 20%) and 79.5% for hip fracture (threshold 3%). Any and hip fracture risks were significantly higher for both methods in women with fracture history in comparison to those without fracture and increased with ageing. The influence of prior fracture and ageing was more evident in Nguyen's nomograms. ROC analyses of any fracture risk in FRAX and Nguyen's methods demonstrated the area under curve (AUC) at 0.833 and 0.879, respectively. Similar analyses for hip fracture demonstrated AUCs for FRAX and Nguyen's technique at 0.726 and 0.850, respectively. The AUCs for Nguyen's nomograms were significantly larger than the AUCs for FRAX (p<0.0001).

CONCLUSION: The mean conformity for any fracture risk is 79.1% and 79.5% for hip fracture. Nguyen's nomograms seem to be more efficient in fracture risk assessment, especially for hip fractures, due to a higher accuracy of the method. The information on the number of falls during the last year and multiple fractures ought to be incorporated into the method of fracture risk prediction.

MINI-ABSTRACT: The degree of conformity was assessed in a group of 2012 women between 10-year FRAX prognosis of fracture and Nguyen et al.'s nomograms. The mean conformity for any fracture risk is 79.1% and 79.5% for hip fracture. Nguyen's nomograms seem to be more efficient in fracture risk assessment due to higher accuracy.}, } @article {pmid20150676, year = {2010}, author = {Mahata, P}, title = {Exploratory consensus of hierarchical clusterings for melanoma and breast cancer.}, journal = {IEEE/ACM transactions on computational biology and bioinformatics}, volume = {7}, number = {1}, pages = {138-152}, doi = {10.1109/TCBB.2008.33}, pmid = {20150676}, issn = {1557-9964}, mesh = {*Algorithms ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/*diagnosis/*metabolism ; Diagnosis, Computer-Assisted/*methods ; Gene Expression Profiling/methods ; Humans ; Melanoma/classification/*diagnosis/*metabolism ; Multigene Family ; Neoplasm Proteins/analysis ; }, abstract = {Finding subtypes of heterogeneous diseases is the biggest challenge in the area of biology. Often, clustering is used to provide a hypothesis for the subtypes of a heterogeneous disease. However, there are usually discrepancies between the clusterings produced by different algorithms. This work introduces a simple method which provides the most consistent clusters across three different clustering algorithms for a melanoma and a breast cancer data set. The method is validated by showing that the Silhouette, Dunne's and Davies-Bouldin's cluster validation indices are better for the proposed algorithm than those obtained by k-means and another consensus clustering algorithm. The hypotheses of the consensus clusters on both the data sets are corroborated by clear genetic markers and 100 percent classification accuracy. In Bittner et al.'s melanoma data set, a previously hypothesized primary cluster is recognized as the largest consensus cluster and a new partition of this cluster into two subclusters is proposed. In van't Veer et al.'s breast cancer data set, previously proposed "basal" and "luminal A" subtypes are clearly recognized as the two predominant clusters. Furthermore, a new hypothesis is provided about the existence of two subgroups within the "basal" subtype in this data set. The clusters of van't Veer's data set is also validated by high classification accuracy obtained in the data set of van de Vijver et al.}, } @article {pmid20142150, year = {2010}, author = {Masoumi, N and Bastani, D and Najarian, S and Ganji, F and Farmanzad, F and Seddighi, AS}, title = {Mathematical modeling of CSF pulsatile hydrodynamics based on fluid-solid interaction.}, journal = {IEEE transactions on bio-medical engineering}, volume = {57}, number = {6}, pages = {1255-1263}, doi = {10.1109/TBME.2009.2037975}, pmid = {20142150}, issn = {1558-2531}, mesh = {Brain Neoplasms/*physiopathology ; Cerebral Ventricles/*physiopathology ; *Cerebrospinal Fluid ; Computer Simulation ; Humans ; *Intracranial Pressure ; *Models, Neurological ; *Pulsatile Flow ; }, abstract = {Intracranial pressure (ICP) is derived from cerebral blood pressure and cerebrospinal fluid (CSF) circulatory dynamics and can be affected in the course of many diseases. Computer analysis of the ICP time pattern plays a crucial role in the diagnosis and treatment of those diseases. This study proposes the application of Linninger et al.'s [IEEE Trans. Biomed. Eng., vol. 52, no. 4, pp. 557-565, Apr. 2005] fluid-solid interaction model of CSF hydrodynamic in ventricular system based on our clinical data from a group of patients with brain parenchyma tumor. The clinical experiments include the arterial blood pressure (ABP), venous blood pressure, and ICP in the subarachnoid space (SAS). These data were used as inputs to the model that predicts the intracranial dynamic phenomena. In addition, the model has been modified by considering CSF pulsatile production rate as the major factor of CSF motion. The approximations of ventricle enlargement, CSF pressure distribution in the ventricular system and CSF velocity magnitude in the aqueduct and foramina were obtained in this study. The observation of reversal flow in the CSF flow pattern due to brain tissue compression is another finding in our investigation. Based on the experimental results, no existence of large transmural pressure differences were found in the brain system. The measured pressure drop in the ventricular system was less than 5 Pa. Moreover, the CSF flow pattern, ICP distribution, and velocity magnitude were in good agreement with the published models and CINE (phase-contrast magnetic resonance imaging) experiments, respectively.}, } @article {pmid20138892, year = {2010}, author = {Liu, F and Gao, YG and Gruebele, M}, title = {A survey of lambda repressor fragments from two-state to downhill folding.}, journal = {Journal of molecular biology}, volume = {397}, number = {3}, pages = {789-798}, pmid = {20138892}, issn = {1089-8638}, support = {P30 EB009998/EB/NIBIB NIH HHS/United States ; P41 RR008630/RR/NCRR NIH HHS/United States ; R01 GM093318/GM/NIGMS NIH HHS/United States ; }, mesh = {Bacteriophages ; Crystallography, X-Ray ; Kinetics ; Models, Chemical ; *Models, Molecular ; Mutation/genetics ; *Protein Folding ; Protein Structure, Tertiary ; Repressor Proteins/*chemistry/genetics/metabolism ; Thermodynamics ; Viral Regulatory and Accessory Proteins/*chemistry/genetics/metabolism ; }, abstract = {We survey the two-state to downhill folding transition by examining 20 lambda(6-85)* mutants that cover a wide range of stabilities and folding rates. We investigated four new lambda(6-85)* mutants designed to fold especially rapidly. Two were engineered using the core remodeling of Lim and Sauer, and two were engineered using Ferreiro et al.'s frustratometer. These proteins have probe-dependent melting temperatures as high as 80 degrees C and exhibit a fast molecular phase with the characteristic temperature dependence of the amplitude expected for downhill folding. The survey reveals a correlation between melting temperature and downhill folding previously observed for the beta-sheet protein WW domain. A simple model explains this correlation and predicts the melting temperature at which downhill folding becomes possible. An X-ray crystal structure with a 1.64-A resolution of a fast-folding mutant fragment shows regions of enhanced rigidity compared to the full wild-type protein.}, } @article {pmid20130945, year = {2010}, author = {Smith, P and Silberberg, A}, title = {Rational maximizing by humans (Homo sapiens) in an ultimatum game.}, journal = {Animal cognition}, volume = {13}, number = {4}, pages = {671-677}, doi = {10.1007/s10071-010-0310-4}, pmid = {20130945}, issn = {1435-9456}, mesh = {Adult ; Altruism ; *Choice Behavior ; *Decision Making ; Female ; *Game Theory ; *Games, Experimental ; Humans ; Male ; Reward ; *Social Behavior ; }, abstract = {In the human mini-ultimatum game, a proposer splits a sum of money with a responder. If the responder accepts, both are paid. If not, neither is paid. Typically, responders reject inequitable distributions, favoring punishing over maximizing. In Jensen et al.'s (Science 318:107-109, 2007) adaptation with apes, a proposer selects between two distributions of raisins. Despite inequitable offers, responders often accept, thereby maximizing. The rejection response differs between the human and ape versions of this game. For humans, rejection is instantaneous; for apes, it requires 1 min of inaction. We replicate Jensen et al.'s procedure in humans with money. When waiting 1 min to reject, humans favor punishing over maximizing; however, when rejection requires 5 min of inaction, humans, like apes, maximize. If species differences in time horizons are accommodated, Jensen et al.'s ape data are reproducible in humans.}, } @article {pmid20116052, year = {2010}, author = {Lam, B}, title = {Are Cantonese-speakers really descriptivists? Revisiting cross-cultural semantics.}, journal = {Cognition}, volume = {115}, number = {2}, pages = {320-329}, doi = {10.1016/j.cognition.2009.12.018}, pmid = {20116052}, issn = {1873-7838}, mesh = {Adolescent ; Adult ; China ; Cognition/physiology ; Cross-Cultural Comparison ; England ; Female ; Humans ; *Language ; Male ; *Psycholinguistics ; *Semantics ; Young Adult ; }, abstract = {In an article in Cognition [Machery, E., Mallon, R., Nichols, S., & Stich, S. (2004). Semantics cross-cultural style. Cognition, 92, B1-B12] present data which purports to show that East Asian Cantonese-speakers tend to have descriptivist intuitions about the referents of proper names, while Western English-speakers tend to have causal-historical intuitions about proper names. Machery et al. take this finding to support the view that some intuitions, the universality of which they claim is central to philosophical theories, vary according to cultural background. Machery et al. conclude from their findings that the philosophical methodology of consulting intuitions about hypothetical cases is flawed vis a vis the goal of determining truths about some philosophical domains like philosophical semantics. In the following study, three new vignettes in English were given to Western native English-speakers, and Cantonese translations were given to native Cantonese-speaking immigrants from a Cantonese community in Southern California. For all three vignettes, questions were given to elicit intuitions about the referent of a proper name and the truth-value of an uttered sentence containing a proper name. The results from this study reveal that East Asian Cantonese-speakers do not differ from Western English-speakers in ways that support Machery et al.'s conclusions. This new data concerning the intuitions of Cantonese-speakers raises questions about whether cross-cultural variation in answers to questions on certain vignettes reveal genuine differences in intuitions, or whether such differences stem from non-intuitional differences, such as differences in linguistic competence.}, } @article {pmid20113770, year = {2009}, author = {Coulter, CE and Anderson, JD and Conture, EG}, title = {Childhood stuttering and dissociations across linguistic domains: a replication and extension.}, journal = {Journal of fluency disorders}, volume = {34}, number = {4}, pages = {257-278}, pmid = {20113770}, issn = {1873-801X}, support = {R01DC00647-01A2/DC/NIDCD NIH HHS/United States ; R01DC000523-14/DC/NIDCD NIH HHS/United States ; R56 DC000523/DC/NIDCD NIH HHS/United States ; R01 DC000523/DC/NIDCD NIH HHS/United States ; 2R56DC00053-14A1/DC/NIDCD NIH HHS/United States ; }, mesh = {*Child Language ; Child, Preschool ; Female ; Humans ; Interpersonal Relations ; Language Tests ; *Linguistics ; Male ; Models, Statistical ; Psycholinguistics ; Speech ; Speech Production Measurement ; *Stuttering ; Vocabulary ; }, abstract = {UNLABELLED: The purpose of this investigation was to replicate the methods of Anderson, Pellowski, and Conture (2005) to determine whether a different sample of preschool children who stutter (CWS) exhibit more dissociations in speech-language abilities than children who do not stutter (CWNS; Study 1) and to examine the relation between dissociations and specific characteristics of stuttering (e.g., most common disfluency type) using a much larger sample size (Study 2). Participants for Study 1 were 40 CWS and 40 CWNS between the ages of 3;0 and 5;11. Participants for Study 2 were the same as for Study 1 plus the 45 CWS and 45 CWNS used by Anderson et al. (2005) for a total of 85 CWS and 85 CWNS. Participants were administered five standardized speech-language (sub)tests and a conversational speech sample was obtained from each participant for the analyses of speech disfluencies/stuttering. Standard scores from the standardized speech-language tests were analyzed using a correlation-based statistical procedure (Bates, Applebaum, Sacedo, Saygin, & Pizzamiglio, 2003) to identify possible dissociations among the speech-language measures. Findings from Study 1 supported Anderson et al.'s findings that CWS exhibited significantly more speech-language dissociations than CWNS. Results from Study 2 further revealed that CWS who exhibited dissociations were more likely to exhibit non-stuttered (other) disfluencies as their most common disfluency type. Findings provide further support for the possibility that dissociations among various aspects of the speech-language system may contribute to the difficulties that some children have establishing normally fluent speech.

EDUCATIONAL OBJECTIVES: The reader will be able to: (a) summarize findings from previous studies examining the speech and language performance of children who do and do not stutter; (b) describe the concept of "dissociations" in the speech and language skills of young children; (c) compare the results of the present study with previous work in this area; and (d) discuss speculations concerning the manner in which dissociations might affect fluency development in children who stutter.}, } @article {pmid20112085, year = {2010}, author = {Williams, DM and Jarrold, C}, title = {Brief report: Predicting inner speech use amongst children with autism spectrum disorder (ASD): the roles of verbal ability and cognitive profile.}, journal = {Journal of autism and developmental disorders}, volume = {40}, number = {7}, pages = {907-913}, pmid = {20112085}, issn = {1573-3432}, mesh = {Child ; Child Development Disorders, Pervasive/*psychology ; *Cognition ; Humans ; Language Development Disorders/psychology ; Linear Models ; Photic Stimulation ; *Speech ; *Thinking ; }, abstract = {Studies of inner speech use in ASD have produced conflicting results. Lidstone et al., J Autism Dev Disord (2009) hypothesised that Cognitive Profile (i.e., discrepancy between non-verbal and verbal abilities) is a predictor of inner speech use amongst children with ASD. They suggested other, contradictory results might be explained in terms of the different composition of ASD samples (in terms of Cognitive Profile) in each study. To test this, we conducted a new analysis of Williams et al.'s, J Child Psychol Psychiatry 48(1): 51-58 (2008) data on inner speech use in ASD. This revealed verbal ability predicted inner speech use on a short-term memory task over and above Cognitive Profile, but not vice versa. This suggests multiple factors determine whether children with ASD employ verbal mediation.}, } @article {pmid20104384, year = {2010}, author = {Mpuchane, SF and Ekosse, GI and Gashe, BA and Morobe, I and Coetzee, SH}, title = {Microbiological characterisation of southern African medicinal and cosmetic clays.}, journal = {International journal of environmental health research}, volume = {20}, number = {1}, pages = {27-41}, doi = {10.1080/09603120903254025}, pmid = {20104384}, issn = {1369-1619}, mesh = {Africa, Southern ; Aluminum Silicates/*analysis/chemistry/classification ; Anti-Bacterial Agents/pharmacology ; Clay ; Cosmetics/*analysis ; Gram-Negative Bacteria/classification/growth & development/*isolation & purification/metabolism ; Gram-Positive Bacteria/classification/growth & development/*isolation & purification/metabolism ; Hydrogen-Ion Concentration ; Microbial Sensitivity Tests ; Microchemistry ; Oxides/*analysis/classification ; Pharmaceutical Preparations/*analysis ; *Soil Microbiology ; }, abstract = {The effects of traditionally used medicinal and cosmetic clays in southern Africa on selected microorganisms were studied using microbiological media. The clay pH, microchemical composition, kind of associated microorganisms and antimicrobial activity of clays against test microorganisms were determined. The clays contained varying numbers of microorganisms which ranged from 0 up to 105 CFU/g. Clay pH ranged from 2.3-8.9. Neither Escherichia coli, nor other faecal coliforms were detected. Clays of pH value of <4 displayed antimicrobial activities. Clays which were active against test microorganisms had Na(2)O, Al(2)O(3), SiO(2), SO(3), CuO or Cl(2)O as major components. Microbial activity of clays was attributed mainly to low pH but cations such as Cu, Al, S or Cl and various anions might have contributed to the microbicidal effects. No antimicrobial activity was established for many of the clays commonly used in the treatment of common ailments of microbial origin.}, } @article {pmid20099959, year = {2010}, author = {Wong, YJ and Kim, SH and Tran, KK}, title = {Asian Americans' adherence to Asian values, attributions about depression, and coping strategies.}, journal = {Cultural diversity & ethnic minority psychology}, volume = {16}, number = {1}, pages = {1-8}, doi = {10.1037/a0015045}, pmid = {20099959}, issn = {1099-9809}, mesh = {*Adaptation, Psychological ; Adult ; Asian/*psychology ; Chi-Square Distribution ; Depression/*psychology ; Female ; Humans ; Male ; Models, Psychological ; Psychological Tests ; Social Responsibility ; Social Values/*ethnology ; Young Adult ; }, abstract = {Using Brickman et al.'s (1982) theoretical framework of responsibility attributions, the authors examined the relationships among adherence to Asian values, attributions about the cause of and solution to depression, and preferred coping strategies in a nonclinical sample of Asian Americans. Results of a path analysis (N = 238) indicate that attribution of cause fully mediated the relations between adherence to Asian values and use of coping strategies. Adherence to Asian values was positively related to attributing the cause of depression to internal factors, which was in turn associated with greater use of disengagement coping strategies and decreased use of engagement coping strategies. In addition, an internal attribution for the solution to depressive symptoms was related to more reliance on engagement coping strategies and a lower use of disengagement coping strategies. Practical implications of the results are discussed.}, } @article {pmid20099548, year = {2009}, author = {Turnipseed, DL and Bacon, CM}, title = {Relation of organizational citizenship behavior and locus of control.}, journal = {Psychological reports}, volume = {105}, number = {3 Pt 1}, pages = {857-864}, doi = {10.2466/PR0.105.3.857-864}, pmid = {20099548}, issn = {0033-2941}, mesh = {Adult ; Commerce/education ; Efficiency, Organizational ; Female ; Humans ; *Internal-External Control ; Male ; *Personnel Loyalty ; *Personnel Selection ; *Social Values ; Students/psychology ; Young Adult ; }, abstract = {The relation of organizational citizenship behavior and locus of control was assessed in a sample of 286 college students (52% men; M age = 24 yr.) who worked an average of 26 hr. per week. Measures were Spector's Work Locus of Control Scale and Podsakoff, et al.'s Organization Citizenship Behavior scale. Hierarchical multiple regressions indicated positive association of scores on work locus of control with scores on each of the four tested dimensions of organizational citizenship, as well as total organizational citizenship behavior.}, } @article {pmid20088605, year = {2010}, author = {Huang, SY and Zou, X}, title = {Inclusion of solvation and entropy in the knowledge-based scoring function for protein-ligand interactions.}, journal = {Journal of chemical information and modeling}, volume = {50}, number = {2}, pages = {262-273}, pmid = {20088605}, issn = {1549-960X}, support = {R21 GM088517/GM/NIGMS NIH HHS/United States ; GM088517/GM/NIGMS NIH HHS/United States ; }, mesh = {Computational Biology ; Computer Simulation ; Databases, Protein ; *Entropy ; Ligands ; Models, Molecular ; Protein Binding ; Protein Conformation ; Proteins/chemistry/*metabolism ; Reproducibility of Results ; Solvents/*chemistry ; }, abstract = {The effects of solvation and entropy play a critical role in determining the binding free energy in protein-ligand interactions. Despite the good balance between speed and accuracy, no current knowledge-based scoring functions account for the effects of solvation and configurational entropy explicitly due to the difficulty in deriving the corresponding pair potentials and the resulting double counting problem. In the present work, we have included the solvation effect and configurational entropy in the knowledge-based scoring function by an iterative method. The newly developed scoring function has yielded a success rate of 91% in identifying near-native binding modes with Wang et al.'s benchmark of 100 diverse protein-ligand complexes. The results have been compared with the results of 15 other scoring functions for validation purpose. In binding affinity prediction, our scoring function has yielded a correlation of R(2) = 0.76 between the predicted binding scores and the experimentally measured binding affinities on the PMF validation sets of 77 diverse complexes. The results have been compared with R(2) of four other well-known knowledge-based scoring functions. Finally, our scoring function was also validated on the large PDBbind database of 1299 protein-ligand complexes and yielded a correlation coefficient of 0.474. The present computational model can be applied to other scoring functions to account for solvation and entropic effects.}, } @article {pmid20079555, year = {2010}, author = {Penke, L and Deary, IJ}, title = {Some guidelines for structural equation modelling in cognitive neuroscience: the case of Charlton et al.'s study on white matter integrity and cognitive ageing.}, journal = {Neurobiology of aging}, volume = {31}, number = {9}, pages = {1656-60; discussion 1561-6}, doi = {10.1016/j.neurobiolaging.2009.10.019}, pmid = {20079555}, issn = {1558-1497}, support = {G0700704/MRC_/Medical Research Council/United Kingdom ; G0701120/MRC_/Medical Research Council/United Kingdom ; 82800/MRC_/Medical Research Council/United Kingdom ; /BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Aged ; Aged, 80 and over ; Aging/metabolism/*pathology ; Brain/metabolism/*pathology/physiopathology ; Cognition/physiology ; Computer Simulation ; Diffusion Magnetic Resonance Imaging/*methods ; Disease Progression ; Female ; Humans ; Male ; Memory Disorders/metabolism/*pathology/physiopathology ; Memory, Short-Term/physiology ; Mental Processes/physiology ; Middle Aged ; Models, Theoretical ; Nerve Fibers, Myelinated/metabolism/*pathology ; Nerve Net/metabolism/pathology/physiopathology ; Neural Pathways/metabolism/pathology/physiopathology ; Neuropsychological Tests ; Prospective Studies ; Reaction Time/physiology ; Wallerian Degeneration/metabolism/*pathology/physiopathology ; }, abstract = {Charlton et al. (2008) (Charlton, R.A., Landua, S., Schiavone, F., Barrick, T.R., Clark, C.A., Markus, H.S., Morris, R.G.A., 2008. Structural equation modelling investigation of age-related variance in executive function and DTI-measured white matter change. Neurobiol. Aging 29, 1547-1555) presented a model that suggests a specific age-related effect of white matter integrity on working memory. We illustrate potential pitfalls of structural equation modelling by criticizing their model for (a) its neglect of latent variables, (b) its complexity, (c) its questionable causal assumptions, (d) the use of empirical model reduction, (e) the mix-up of theoretical perspectives, and (f) the failure to compare alternative models. We show that a more parsimonious model, based solely on the well-established general factor of cognitive ability, fits their data at least as well. Importantly, when modelled this way there is no support for a role of white matter integrity in cognitive aging in this sample, indicating that their conclusion is strongly dependent on how the data are analysed. We suggest that evidence from more conclusive study designs is needed.}, } @article {pmid20069831, year = {2009}, author = {Miller, JR and Siegert, PY and Amimo, FA and Walker, ED}, title = {Designation of chemicals in terms of the locomotor responses they elicit from insects: an update of Dethier et al. (1960).}, journal = {Journal of economic entomology}, volume = {102}, number = {6}, pages = {2056-2060}, doi = {10.1603/029.102.0606}, pmid = {20069831}, issn = {0022-0493}, support = {U01 AI058542/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Female ; Insect Repellents/*pharmacology ; Insecta/*drug effects ; Locomotion/*drug effects ; Terminology as Topic ; }, abstract = {A scheme updating that of Dethier et al. (1960) (J. Econ. Entomol. 53: 134-136) for chemicals influencing insect locomotor behavior is introduced. Attractant, repellent, and arrestant retain their previous definitions. However, attractants or repellents are now recognized to operate both by kinetic and tactic mechanisms. Locomotor initiator is a new term for stimuli that activate normal levels of kinetic locomotion. Locomotor stimulant is reserved for activation of abnormally high kinetic locomotion, like that arising upon sublethal exposure to certain insecticides. The new terms engagent and disengagent apply to chemicals that, by their effects on locomotion, increase or decrease interaction with the source of stimulation, respectively. With these clarifications, insect behavioral terms unique to medical entomology but contradicting Dethier et al.'s classical scheme can be reconciled with the vocabulary of formal behavioral science.}, } @article {pmid20068095, year = {2010}, author = {Fan, X and Shi, L and Fang, H and Cheng, Y and Perkins, R and Tong, W}, title = {DNA microarrays are predictive of cancer prognosis: a re-evaluation.}, journal = {Clinical cancer research : an official journal of the American Association for Cancer Research}, volume = {16}, number = {2}, pages = {629-636}, doi = {10.1158/1078-0432.CCR-09-1815}, pmid = {20068095}, issn = {1557-3265}, mesh = {*Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Humans ; Neoplasms/*diagnosis/*genetics ; *Oligonucleotide Array Sequence Analysis ; Prognosis ; Validation Studies as Topic ; }, abstract = {PURPOSE: The reliability of microarray-based cancer prognosis is questioned by Michiels et al. They reanalyzed seven studies published in the prominent journals as successful stories of microarray-based cancer prognosis and concluded that the originally reported assessments are over optimistic. We set to investigate the reality of microarrays for predicting cancer prognosis by using the same data sets with commonly accepted data analysis approaches.

EXPERIMENT DESIGN: Michiels et al.'s analysis protocol used a correlation-based feature selection method, split sample validation, and a nearest-centroid rule classifier. We examined their results through systematically replacing their analysis approaches with other commonly used methods as a parameter study. In addition, we applied a widely accepted permutation test in conjunction with 5-fold cross-validation to verify Michiels et al.'s findings.

RESULTS: The stability of signature genes is likely obtained when a fold change-based feature selection method is applied. When cross-validation procedures are used to replace Michiels et al.'s split sample validation, only one of the seven studies yielded uninformative classifiers. The permutation test reveals that the confidence interval based on the split sample used in the Michiels et al.'s review is not a rigorous and robust approach to assess the validity of a classifier.

CONCLUSIONS: We concluded that the use of DNA microarrays for cancer prognosis can be demonstrated. We also stressed that caution should be exercised when a general conclusion is withdrawn based on a single statistical practice without alternative validation, which can leave a false impression and pessimistic perspective for emerging biomarker methodologies to advance cancer research.}, } @article {pmid21386230, year = {2010}, author = {Chowdhury, SS and Deo, PS and Jayannavar, AM and Manninen, M}, title = {S-matrix formulation of mesoscopic systems and evanescent modes.}, journal = {Journal of physics. Condensed matter : an Institute of Physics journal}, volume = {22}, number = {1}, pages = {015601}, doi = {10.1088/0953-8984/22/1/015601}, pmid = {21386230}, issn = {1361-648X}, abstract = {Validity of the Landauer-Buttiker formalism for studying linear transport in mesoscopic systems is well established theoretically as well as experimentally. Akkermans et al (1991 Phys. Rev. Lett. 66 76) have shown that the formalism can be extended to study thermodynamic properties like persistent currents. This extension was verified for simple one-dimensional systems. We study the applicability of Akkermans et al' s formula for quasi-one-dimensional systems with several conducting channels. In the case that all modes are propagating the formula is still valid but in the case of evanescent modes it requires reinterpretation.}, } @article {pmid20063960, year = {2010}, author = {Matthews, RA and Kath, LM and Barnes-Farrell, JL}, title = {A short, valid, predictive measure of work-family conflict: item selection and scale validation.}, journal = {Journal of occupational health psychology}, volume = {15}, number = {1}, pages = {75-90}, doi = {10.1037/a0017443}, pmid = {20063960}, issn = {1939-1307}, mesh = {Adult ; Cross-Sectional Studies ; *Family Conflict/psychology ; Female ; Humans ; Male ; Middle Aged ; Surveys and Questionnaires/*standards ; *Work Schedule Tolerance ; }, abstract = {The purpose of this research is to develop an abbreviated version of Carlson, Kacmar, and Williams's (2000) multidimensional measure of work-family conflict. The abbreviated measure would have high utility in research situations in which a measure representative of the entire theoretical construct is desired, but the use of a long measure is precluded, as in diary and longitudinal designs. Two 3-item abbreviated measures based on Carlson et al.'s multidimensional measures were developed, 1 to assess work-to-family conflict and 1 to assess family-to-work conflict. Two samples were used to provide concurrent and predictive validity evidence for the abbreviated measure. Results from Study 1 indicate that the abbreviated measure has the expected factor structure and exhibited concurrent and predictive validity that replicated results found with Carlson et al.'s 18-item measure. Results from Study 2 provide additional psychometric and construct validity evidence for the abbreviated measure; the abbreviated measure was internally consistent, exhibited good test-retest reliability, and was systematically related to measures of role stressors, work-family balance, and well-being outcomes.}, } @article {pmid20063920, year = {2010}, author = {Bremner, JD}, title = {Cognitive processes in dissociation: comment on Giesbrecht et al. (2008).}, journal = {Psychological bulletin}, volume = {136}, number = {1}, pages = {1-6; discussion 7-11}, pmid = {20063920}, issn = {1939-1455}, support = {R01 MH056120/MH/NIMH NIH HHS/United States ; T32 MH067547/MH/NIMH NIH HHS/United States ; R01 MH56120/MH/NIMH NIH HHS/United States ; T32 MH067547-01/MH/NIMH NIH HHS/United States ; K24 MH076955/MH/NIMH NIH HHS/United States ; R01 HL088726/HL/NHLBI NIH HHS/United States ; }, mesh = {Cognition Disorders/diagnosis/*epidemiology ; Dissociative Disorders/diagnosis/*epidemiology/psychology ; Female ; Humans ; Hypnosis ; Male ; Memory Disorders/diagnosis/epidemiology ; Neuropsychological Tests ; Prevalence ; Stress Disorders, Post-Traumatic/diagnosis/epidemiology/therapy ; }, abstract = {In their recent review "Cognitive Processes in Dissociation: An Analysis of Core Theoretical Assumptions," published in Psychological Bulletin, Giesbrecht, Lynn, Lilienfeld, and Merckelbach have challenged the widely accepted trauma theory of dissociation, which holds that dissociative symptoms are caused by traumatic stress. In doing so, the authors have outlined a series of links between various constructs--such as fantasy proneness, cognitive failures, absorption, suggestibility, altered information-processing, dissociation, and amnesia--claiming that these linkages lead to the false conclusion that trauma causes dissociation. A review of the literature, however, shows that these are not necessarily related constructs. Careful examination of their arguments reveals no basis for the conclusion that there is no association between trauma and dissociation. The current comment offers a critical review and rebuttal of Giesbrecht et al.'s argument that there is no relationship between trauma and dissociation.}, } @article {pmid20054559, year = {2010}, author = {Vered, M and Dayan, D and Dobriyan, A and Yahalom, R and Shalmon, B and Barshack, I and Bedrin, L and Talmi, YP and Taicher, S}, title = {Oral tongue squamous cell carcinoma: recurrent disease is associated with histopathologic risk score and young age.}, journal = {Journal of cancer research and clinical oncology}, volume = {136}, number = {7}, pages = {1039-1048}, pmid = {20054559}, issn = {1432-1335}, mesh = {Adult ; Age Factors ; Aged ; Aged, 80 and over ; Carcinoma, Squamous Cell/*diagnosis ; Female ; Follow-Up Studies ; Humans ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Multivariate Analysis ; Neoplasm Recurrence, Local/*diagnosis/pathology ; Risk Factors ; Tongue Neoplasms/*diagnosis ; Young Adult ; }, abstract = {PURPOSE: To apply the Brandwein-Gensler et al.'s histopathologic risk score (RS) system and to evaluate its impact on locoregional recurrence and overall survival in a series of cases of oral tongue cancer, along with variables of patient age and margin status.

METHODS: Sections of the resection specimens (N = 50) were submitted to a RS assignment of three components: the worst pattern of invasion, lymphocytic infiltration and perineural invasion. Risk scores of 0-2 were classified as low-to-intermediate and RSs > or = 3 were classified as high with respect to recurrence and survival. Margins were considered as "clean" if the tumor was > or = 5 mm away from them, otherwise they were defined as "positive". Patients < or = 60 years were considered "young" and those >60 years "old". Kaplan-Meier survival analysis with univariate and Cox multivariate regression model with stepwise forward selection tests were used.

RESULTS: Univariate analysis showed that locoregional recurrence was negatively influenced by high RSs (P = 0.011), "young" age (P = 0.027) and positive margins (P = 0.027). Multivariate analysis revealed that the risk of recurrence was increased by high RSs (hazard ratio 11.14; P = 0.022) and "young" age (hazard ratio 3.41; P = 0.022). "Young" patients with high RSs had a higher frequency of recurrence rate compared to "young" patients with low-to-intermediate scores (P = 0.008) and "old" patients with low-to-intermediate and high RSs (P = 0.012 and P = 0.011, respectively).

CONCLUSIONS: The histopathologic RS can serve to identify a subgroup of patients <60 years who have a high recurrence rate of oral tongue cancer, irrespective of the margin status.}, } @article {pmid20051310, year = {2010}, author = {Ehlers, A and Bisson, J and Clark, DM and Creamer, M and Pilling, S and Richards, D and Schnurr, PP and Turner, S and Yule, W}, title = {Do all psychological treatments really work the same in posttraumatic stress disorder?.}, journal = {Clinical psychology review}, volume = {30}, number = {2}, pages = {269-276}, pmid = {20051310}, issn = {1873-7811}, support = {069777/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Clinical Trials as Topic ; Humans ; Life Change Events ; *Meta-Analysis as Topic ; Psychotherapy/*methods ; Selection Bias ; Stress Disorders, Post-Traumatic/*therapy ; }, abstract = {A recent meta-analysis by Benish, Imel, and Wampold (2008, Clinical Psychology Review, 28, 746-758) concluded that all bona fide treatments are equally effective in posttraumatic stress disorder (PTSD). In contrast, seven other meta-analyses or systematic reviews concluded that there is good evidence that trauma-focused psychological treatments (trauma-focused cognitive behavior therapy and eye movement desensitization and reprocessing) are effective in PTSD; but that treatments that do not focus on the patients' trauma memories or their meanings are either less effective or not yet sufficiently studied. International treatment guidelines therefore recommend trauma-focused psychological treatments as first-line treatments for PTSD. We examine possible reasons for the discrepant conclusions and argue that (1) the selection procedure of the available evidence used in Benish et al.'s (2008)meta-analysis introduces bias, and (2) the analysis and conclusions fail to take into account the need to demonstrate that treatments for PTSD are more effective than natural recovery. Furthermore, significant increases in effect sizes of trauma-focused cognitive behavior therapies over the past two decades contradict the conclusion that content of treatment does not matter. To advance understanding of the optimal treatment for PTSD, we recommend further research into the active mechanisms of therapeutic change, including treatment elements commonly considered to be non-specific. We also recommend transparency in reporting exclusions in meta-analyses and suggest that bona fide treatments should be defined on empirical and theoretical grounds rather than by judgments of the investigators' intent.}, } @article {pmid20045746, year = {2010}, author = {Arora, S and Sevdalis, N}, title = {Systems Approach to daily clinical care.}, journal = {International journal of surgery (London, England)}, volume = {8}, number = {2}, pages = {164-166}, doi = {10.1016/j.ijsu.2009.12.007}, pmid = {20045746}, issn = {1743-9159}, mesh = {*Clinical Competence ; Cooperative Behavior ; Female ; General Surgery/standards/trends ; Humans ; Interprofessional Relations ; Male ; Medical Errors/*prevention & control ; Operating Rooms ; Organizational Culture ; Patient Care Team/organization & administration ; Physician-Patient Relations ; Practice Patterns, Physicians'/organization & administration ; Program Evaluation ; *Quality Assurance, Health Care ; Safety Management/*organization & administration ; *Systems Analysis ; United Kingdom ; }, abstract = {Safety and quality of healthcare provision are affected by a number of factors. These factors include the clinical skills of the treating surgeon or other physician, but also the way practitioners think and behave as members of a healthcare team, and the clinical environment in which care is provided. We first discuss Bahal et al.'s paper as a demonstration of the Systems Approach to clinical performance and patient safety. We then highlight recent advances driven by the Systems Approach in understanding and measuring clinical decision-making, teamworking, and the clinical environment. We conclude that human factors research can provide an understanding of how to balance conflicting opinions and priorities in clinical care with the best interests of the patient, in a manner which allows each doctor to fulfil their duty of care.}, } @article {pmid20032433, year = {2009}, author = {Eskelinen, M and Ollonen, P}, title = {Psychosocial risk scale (PRS) for breast cancer in patients with breast disease: a prospective case-control study in Kuopio, Finland.}, journal = {Anticancer research}, volume = {29}, number = {11}, pages = {4765-4770}, pmid = {20032433}, issn = {1791-7530}, mesh = {Breast Diseases/pathology/*psychology ; Breast Neoplasms/pathology/*psychology ; Case-Control Studies ; Female ; Humans ; Middle Aged ; Prospective Studies ; Psychological Tests ; Risk Factors ; Surveys and Questionnaires ; }, abstract = {BACKGROUND: In 1982, Wirsching et al. introduced a psychosocial risk scale (PRS) for psychological identification of breast cancer patients before biopsy. To our knowledge, the associations between PRS and risk of breast cancer are rarely considered together in a prospective study.

PATIENTS AND METHODS: This study is an extension of the Kuopio Breast Cancer Study. Women with breast symptoms were referred by physicians to the Kuopio University Hospital (Finland) and were asked to participate in this study. These women (n=115) were interviewed, and all study variables were obtained before any diagnostic procedures were carried out, so neither the investigator nor the participants knew the final diagnosis of breast symptoms at the time of the interview. The research method used was the semistructured in-depth interview method. The investigator used the Montgomery-Asberg depression rating scale (MADRS) to evaluate the depression of the study participants. All participants were also asked to complete standardized questionnaires (Beck depression inventory and Spielberger trait inventory). The investigator estimated the PRS using a 3-point scale: grade I, low psychosocial risk; grade II, mild/moderate psychosocial risk; grade III, high psychosocial risk for breast cancer.

RESULTS: The clinical examination and biopsy showed breast cancer in 34 patients, benign breast disease in 53 patients, and 28 individuals were shown to be healthy (HSS). The results indicated that breast cancer patients used more idealization of childhood, and motherhood (p=0.04) than did the other groups. PRS was significantly associated with increased breast cancer risk (p=0.05).

CONCLUSION: The results of this study support a moderate association between Wirsching et al.'s PRS score and breast cancer risk. However, the biological explanation for such an association is unclear and the exact effects of psychological factors on the various hormones relevant to development of breast cancer are at present poorly defined.}, } @article {pmid20025657, year = {2009}, author = {Himler, AG and Machado, CA}, title = {Host specificity, phenotype matching and the evolution of reproductive isolation in a coevolved plant-pollinator mutualism.}, journal = {Molecular ecology}, volume = {18}, number = {24}, pages = {4988-4990}, doi = {10.1111/j.1365-294X.2009.04429.x}, pmid = {20025657}, issn = {1365-294X}, mesh = {Animals ; *Biological Evolution ; *Gene Flow ; *Genetic Fitness ; Moths/genetics/physiology ; Phenotype ; *Pollination ; Species Specificity ; Yucca/genetics ; }, abstract = {Coevolutionary interactions between plants and their associated pollinators and seed dispersers are thought to have promoted the diversification of flowering plants (Raven 1977; Regal 1977; Stebbins 1981). The actual mechanisms by which pollinators could drive species diversification in plants are not fully understood. However, it is thought that pollinator host specialization can influence the evolution of reproductive isolation among plant populations because the pollinator's choice of host is what determines patterns of gene flow in its host plant, and host choice may also have important consequences on pollinator and host fitness (Grant 1949; Bawa 1992). In this issue of Molecular Ecology, Smith et al. (2009) present a very interesting study that addresses how host specialization affects pollinator fitness and patterns of gene flow in a plant host. Several aspects of this study match elements of a seminal mathematical model of plant-pollinator codivergence (Kiester et al. 1984) suggesting that reciprocal selection for matched plant and pollinator reproductive traits may lead to speciation in the host and its pollinator when there is strong host specialization and a pattern of geographic subdivision. Smith et al.'s study represents an important step to fill the gap in our understanding of how reciprocal selection may lead to speciation in coevolved plant-pollinator mutualisms.}, } @article {pmid20025409, year = {2009}, author = {Wilson-Genderson, M and Pruchno, RA and Cartwright, FP}, title = {Effects of caregiver burden and satisfaction on affect of older end-stage renal disease patients and their spouses.}, journal = {Psychology and aging}, volume = {24}, number = {4}, pages = {955-967}, pmid = {20025409}, issn = {1939-1498}, support = {R01 NR005237/NR/NINR NIH HHS/United States ; R01 NR-05237/NR/NINR NIH HHS/United States ; }, mesh = {*Affect ; Aged ; Caregivers/*psychology ; *Cost of Illness ; Female ; Humans ; Interviews as Topic ; Kidney Failure, Chronic/*psychology ; Male ; Middle Aged ; *Personal Satisfaction ; Spouses/*psychology ; }, abstract = {We examined the extent to which a 2-factor model of affect explains how the burdens and satisfactions experienced by caregivers influence their own well-being and that of the spouses for whom they provide care. Using data from 315 older patients with end-stage renal disease and their spouses, we extended tests of Lawton et al.'s (1991) 2-factor model both longitudinally and dyadically. Multilevel modeling analyses partially support the 2-factor model. Consistent with the model, mean caregiver burden has a stronger effect on both caregiver and patient negative affect than does mean caregiver satisfaction. Contrary to the model, mean caregiver satisfaction has an effect on caregiver positive affect that is similar to that of mean caregiver burden, and it has no effect on patient positive affect. Time-varying effects of caregiver burden are consistent with the 2-factor model for caregiver but not patient negative affect. Time-varying effects of caregiver satisfaction are not consistent with the 2-factor model for either patients or caregivers. Results highlight the powerful role of caregiver burden for both caregivers and patients and suggest important new directions for conducting health-related research with late-life marital dyads.}, } @article {pmid20012253, year = {2009}, author = {Beuhler, MC and Dulaney, AR}, title = {In response to Barbee et al.'s "Analysis of mushroom exposures in Texas requiring hospitalization, 2005-2006".}, journal = {Journal of medical toxicology : official journal of the American College of Medical Toxicology}, volume = {5}, number = {4}, pages = {260}, pmid = {20012253}, issn = {1556-9039}, mesh = {*Hospitalization/statistics & numerical data ; Humans ; Mushroom Poisoning/epidemiology/*therapy ; *Poison Control Centers/statistics & numerical data ; Research Design ; Texas/epidemiology ; Time Factors ; }, } @article {pmid20012252, year = {2009}, author = {Gillman, K}, title = {In response to Morris et al.'s "Neuroleptic malignant syndrome developing after acute overdose with olanzapine and chlorpromazine".}, journal = {Journal of medical toxicology : official journal of the American College of Medical Toxicology}, volume = {5}, number = {4}, pages = {259}, pmid = {20012252}, issn = {1556-9039}, mesh = {Antipsychotic Agents/*poisoning ; Benzodiazepines/*poisoning ; Bromocriptine/therapeutic use ; Chlorpromazine/*poisoning ; Disease Progression ; Dopamine Agonists/therapeutic use ; Drug Overdose ; Humans ; Neuroleptic Malignant Syndrome/drug therapy/*etiology ; Olanzapine ; Serotonin Receptor Agonists/therapeutic use ; Treatment Outcome ; }, } @article {pmid20005811, year = {2009}, author = {Rebeiz, M and Ramos-Womack, M and Jeong, S and Andolfatto, P and Werner, T and True, J and Stern, DL and Carroll, SB}, title = {Evolution of the tan locus contributed to pigment loss in Drosophila santomea: a response to Matute et al.}, journal = {Cell}, volume = {139}, number = {6}, pages = {1189-1196}, doi = {10.1016/j.cell.2009.11.004}, pmid = {20005811}, issn = {1097-4172}, support = {F32-GM78972/GM/NIGMS NIH HHS/United States ; GM063622-06A1/GM/NIGMS NIH HHS/United States ; //Howard Hughes Medical Institute/United States ; }, mesh = {Animals ; Chimera ; Chromosomal Proteins, Non-Histone/*metabolism ; DNA-Binding Proteins/*metabolism ; Drosophila/*genetics ; Drosophila Proteins/*metabolism ; *Evolution, Molecular ; Pigmentation/*genetics ; Species Specificity ; X Chromosome ; }, abstract = {We have shown previously that the loss of abdominal pigmentation in D. santomea relative to its sister species D. yakuba resulted, in part, from cis-regulatory mutations at the tan locus. Matute et al. claim, based solely upon extrapolation from genetic crosses of D. santomea and D. melanogaster, a much more divergent species, that at least four X chromosome regions but not tan are responsible for pigmentation differences. Here, we provide additional evidence from introgressions of D. yakuba genes into D. santomea that support a causative role for tan in the loss of pigmentation and present analyses that contradict Matute et al.'s claims. We discuss how the choice of parental species and other factors affect the ability to identify loci responsible for species divergence, and we affirm that all of our previously reported results and conclusions stand.}, } @article {pmid20004117, year = {2010}, author = {Norman, E and Price, MC}, title = {Measuring "intuition" in the SRT generation task.}, journal = {Consciousness and cognition}, volume = {19}, number = {1}, pages = {475-477}, doi = {10.1016/j.concog.2009.11.004}, pmid = {20004117}, issn = {1090-2376}, mesh = {Awareness ; Humans ; *Intuition ; *Judgment ; Learning ; *Orientation ; Pattern Recognition, Visual ; Psychomotor Performance ; Reaction Time ; *Serial Learning ; *Unconscious, Psychology ; }, abstract = {We address some concerns related to the use of post-trial attribution judgments, originally developed for artificial grammar learning (AGL), during the version of the serial reaction time (SRT) task used by Fu, Dienes, and Fu (2010). In particular, intuition attributions, which are central to Fu et al.'s arguments, seem problematic: This attribution is likely to be made when stimuli contain several competing sources of information to which subjective feelings could be attributed. The interpretation of intuition attributions in Fu et al.'s SRT generation task is problematic because the procedure involved a 2-element sequence where items varied only in position. In our view, responses categorised as intuitions might have been a variety of guess response where neither judgement knowledge nor structural knowledge were conscious. The results would then be compatible with previous findings showing that people can control the use of unconscious structural knowledge even when judgement knowledge is unconscious.}, } @article {pmid19947613, year = {2010}, author = {Nguyen, PT and Nguyen, AV}, title = {Drainage, rupture, and lifetime of deionized water films: effect of dissolved gases?.}, journal = {Langmuir : the ACS journal of surfaces and colloids}, volume = {26}, number = {5}, pages = {3356-3363}, doi = {10.1021/la9031333}, pmid = {19947613}, issn = {1520-5827}, abstract = {Gas bubbles coalesce in deionized (DI) water because the water (foam) films between the bubbles are not stable. The so-called hydrophobic attraction has been suggested as the cause of the film instability and the bubble coalescence. In this work, microinterferometry experiments show that foam films of ultrapure DI water can last up to 10 s and the contact time between the two gas bubble surfaces at close proximity (approximately 1 microm separation distance) significantly influences the film drainage, rupture, and lifetime. Specifically, when the two bubbles were first brought into contact, the films instantly ruptured at 0.5 microm thickness. However, the film drainage rate and rupture thickness sharply decreased and the film lifetime steeply increased with increasing contact time up to 10 min, but then they leveled off. The constant thickness of film rupture was around 35 nm. Possible contamination was vigorously investigated and ruled out. It is argued that migration of gases inherently dissolved in water might cause the transient behavior of the water films at the short contact time. The film drainage rate and instability at the long contact time were analyzed employing Eriksson et al.'s phenomenological theory of long-range hydrophobic attraction (Eriksson, J. C.; Ljunggren, S.; Claesson, P. M., J. Chem. Soc., Faraday Trans. 2 1989, 85, 163-176) and the hypothesis of water molecular structure modified by dissolved gases, and the extended Stefan-Reynolds theory by incorporating the mobility of the air-DI-water interfaces.}, } @article {pmid19946701, year = {2010}, author = {Nolte, HW and Noakes, TD}, title = {Comments on Baker et al.'s "change in body mass accurately and reliably predicts change in body water after endurance exercise".}, journal = {European journal of applied physiology}, volume = {108}, number = {5}, pages = {1061-1064}, pmid = {19946701}, issn = {1439-6327}, mesh = {Body Water/*metabolism/physiology ; Body Weight/*physiology ; Body Weights and Measures/methods/standards ; Calibration ; Carbohydrate Metabolism/physiology ; Exercise/*physiology ; Humans ; Physical Endurance/*physiology ; Predictive Value of Tests ; Reproducibility of Results ; Time Factors ; }, } @article {pmid19945386, year = {2009}, author = {Griffith, LC}, title = {Attention K-Mart shoppers: blowout on Aisle 7!.}, journal = {Neuron}, volume = {64}, number = {4}, pages = {443-445}, pmid = {19945386}, issn = {1097-4199}, support = {R01 MH067284/MH/NIMH NIH HHS/United States ; }, mesh = {Animals ; Humans ; *Arousal/genetics/physiology ; Circadian Rhythm/genetics/physiology ; *Drosophila Proteins/genetics/physiology ; *Nerve Net/cytology/metabolism/physiology ; *Receptors, Dopamine/genetics/physiology ; *Receptors, Dopamine D1/genetics/physiology ; *Stress, Physiological/genetics/physiology ; }, abstract = {The mechanistic basis of arousal is controversial. In this issue of Neuron, Lebestky et al.'s new study in Drosophila, where dopamine has been shown to be involved in several types of attentional processes, demonstrates that it independently regulates distinct types of arousal. These data provide evidence for molecularly convergent, but anatomically divergent, task-specific arousal circuits.}, } @article {pmid19926366, year = {2010}, author = {Allan, HT and Smith, P}, title = {Are pedagogies used in nurse education research evident in practice?.}, journal = {Nurse education today}, volume = {30}, number = {5}, pages = {476-479}, doi = {10.1016/j.nedt.2009.10.011}, pmid = {19926366}, issn = {1532-2793}, mesh = {*Clinical Competence ; Education, Nursing/*methods ; Education, Nursing, Continuing ; *Evidence-Based Nursing ; *Faculty, Nursing ; Health Knowledge, Attitudes, Practice ; Humans ; Learning ; Nursing Education Research/*methods ; Staff Development ; Teaching/*methods ; Translational Research, Biomedical ; Workplace ; }, abstract = {This paper considers two questions: what pedagogies for teaching nursing are used in nurse education research? Are these pedagogies transferred to learning in the workplace? We argue that there are underpinning pedagogies identified in nurse education research in the area of workplace and work based learning which are broadly qualitative, action orientated and focused on knowledge generation. Such pedagogies are rooted in a philosophy of teaching and learning where learning is seen as active, reflective and socially constructed. We consider possible answers to these questions through an exploration of empirical work by Evans et al. (2009) which has focused on knowledge transfer in the workplace. Their work offers insights into how pedagogies can be applied to nurse education research which in turn may be transferred into the workplace. In particular, they argue that the concept of knowledge transfer is outdated and we should focus instead on how knowledge learnt in one context (the academy) is re-contextualised in another (the workplace). We also draw on Aranda and Law's (2007) paper on the debates concerning the use of sociology in nurse education to explore competing narratives. We conclude that the pedagogies identified in educational research are not transferred to nurse education and practice yet offer an alternative view of knowledge transfer as illustrated by Evans et al.'s work which explores how learning in the workplace may be facilitated more effectively. We conclude that the lack of transfer of nurse education research pedagogies to practice learning undermines the position of nurse teachers within the academy as nurse education becomes a practice or professional discipline without a discrete disciplinary base.}, } @article {pmid19914616, year = {2011}, author = {Buiatti, T and Mussoni, A and Toraldo, A and Skrap, M and Shallice, T}, title = {Two qualitatively different impairments in making rotation operations.}, journal = {Cortex; a journal devoted to the study of the nervous system and behavior}, volume = {47}, number = {2}, pages = {166-179}, doi = {10.1016/j.cortex.2009.10.006}, pmid = {19914616}, issn = {1973-8102}, mesh = {Adult ; Brain/pathology ; Brain Neoplasms/pathology/psychology/surgery ; Cognition/*physiology ; Cognition Disorders/psychology ; Computer Simulation ; Female ; Functional Laterality/physiology ; Humans ; Image Processing, Computer-Assisted ; Imagination/*physiology ; Intervertebral Disc Displacement/surgery ; Lumbar Vertebrae/surgery ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Monte Carlo Method ; Parietal Lobe/pathology ; Photic Stimulation ; Postoperative Complications/psychology ; Prefrontal Cortex/pathology ; Psychomotor Performance/physiology ; Rotation ; Verbal Behavior/physiology ; }, abstract = {It is widely recognized that mental rotation is a cognitive process which engages a distributed cortical network including the frontal, premotor and parietal regions. Like other visual-spatial transformations it could require operations on both metric and categorical spatial representations. Previous reports have implicated respectively the right hemisphere being involved in the metric processing and the left hemisphere in the categorical processing. By using a modified version of the Bricolo et al.'s task (2000), we attempted to establish the cortical regions relevant for the categorical and metric aspects of mental rotation transformations. Two groups of patients were found to be impaired in our study, namely the left prefrontal and the right parietal. In particular, whereas the right parietal group made poor use of categorical information, the left prefrontal patients showed a broader mental rotation impairment with a significant number of metric errors. The results are discussed in terms of the model of Kosslyn et al. (1989) about the possible mental transformation impairments following brain lesions.}, } @article {pmid19912486, year = {2010}, author = {Novara, G and Ficarra, V and D'Elia, C and Secco, S and De Gobbi, A and Cavalleri, S and Artibani, W}, title = {Preoperative criteria to select patients for bilateral nerve-sparing robotic-assisted radical prostatectomy.}, journal = {The journal of sexual medicine}, volume = {7}, number = {2 Pt 1}, pages = {839-845}, doi = {10.1111/j.1743-6109.2009.01589.x}, pmid = {19912486}, issn = {1743-6109}, mesh = {Erectile Dysfunction/etiology ; Follow-Up Studies ; Health Status Indicators ; Humans ; Laparoscopy/*methods ; Male ; *Patient Selection ; Postoperative Complications/etiology ; Prostatectomy/*methods ; Prostatic Neoplasms/*surgery ; Risk Factors ; *Robotics ; Surgery, Computer-Assisted/*methods ; }, abstract = {INTRODUCTION: To date, no study has analyzed the predictors of potency recovery in a robot-assisted laparoscopic radical prostatectomy (RALP) series. A novel risk stratification for erectile function recovery after retropubic radical prostatectomy (RRP) has been proposed recently by Briganti et al. from the University Vita-Salute San Raffaele in Milan, Italy.

AIM: To evaluate the potency rate in a series of consecutive patients who underwent bilateral nerve-sparing RALP, to identify the preoperative predictors of erectile function recovery, and to validate the risk-group stratification of Briganti et al.

METHODS: The clinical records of all patients who underwent RALP for clinically localized prostate cancer between April 2005 and April 2009 were prospectively collected in the Prostate Cancer Padua Database. For the present study, we extracted all consecutive cases receiving a bilateral nerve-sparing technique with a minimum follow-up > or =12 months.

MAIN OUTCOME MEASURES: Twelve-month potency rate after RALP, defined as an International Index of Erectile Function 6 (IIEF-6) score > or =18.

RESULTS: Data showed that 129 out of 208 enrolled patients (62%) were potent 12 months after surgery. Age (hazard ratio [HR]: 2.8; P < 0.001), Charlson score (HR: 2.9; P = 0.007), and baseline IIEF-6 score (HR: 0.8; P < 0.001) were independent predictors of potency recovery at multivariate analysis. According to Briganti et al.'s risk-group stratification, the 12-month potency rate following RALP was 81.9% in the low-risk group, 56.7% in the intermediate-risk group, and 28.6% in the high-risk group (P < 0.001).

CONCLUSIONS: In the era of robotic surgery, the key point for the success of the nerve-sparing technique remains the accurate selection of patients. Age < or =65 years, absence of associated comorbidities, and good preoperative erectile function are the most important preoperative factors to select those patients for whom bilateral nerve-sparing RALP can achieve the best results.}, } @article {pmid19910381, year = {2009}, author = {Halloran, ME and Holmes, EC}, title = {Invited commentary: Evaluating vaccination programs using genetic sequence data.}, journal = {American journal of epidemiology}, volume = {170}, number = {12}, pages = {1464-6; discussion 1467-8}, pmid = {19910381}, issn = {1476-6256}, support = {R01 AI032042/AI/NIAID NIH HHS/United States ; R01 AI32042/AI/NIAID NIH HHS/United States ; }, mesh = {Acute Disease ; Base Sequence ; Bayes Theorem ; Disease Notification ; *Genetic Variation ; Hepatitis B/epidemiology/transmission/*virology ; *Hepatitis B Vaccines ; Hepatitis B virus/*genetics ; Homosexuality, Male ; Humans ; Male ; Molecular Sequence Data ; Netherlands ; Program Evaluation ; }, abstract = {Genomic data will become an increasingly important component of epidemiologic studies in coming years. The authors of the accompanying Journal article, van Ballegooijen et al. (Am J Epidemiol. 2009;170(12):1455-1463), are to be commended for attempting to use the coalescent analysis of viral sequence data to evaluate a hepatitis B vaccination program. Coalescent theory attempts to link the phylogenetic history of populations with rates of population growth and decline. In particular, under certain assumptions, a reduction in genetic diversity can be interpreted as a reduction in disease incidence. However, the authors of this commentary contend that van Ballegooijen et al.'s interpretation of changes in viral genetic diversity as a measure of hepatitis B vaccine effectiveness has major limitations. Because of the potential use of these methods in future vaccination studies, the authors discuss the utility of these methods and the data requirements needed for them to be convincing. First, data sets should be large enough to provide sufficient epidemiologic-scale resolution. Second, data need to reflect sufficiently fine-grained temporal sampling. Third, other processes that can potentially influence genetic diversity and confuse demographic inferences should be considered.}, } @article {pmid19900244, year = {2009}, author = {Brose, LS and Mitchell, J and Bradley, C}, title = {Comments on Speight et al.'s 'Not all roads lead to Rome-a review of quality of life measurement in adults with diabetes'.}, journal = {Diabetic medicine : a journal of the British Diabetic Association}, volume = {26}, number = {10}, pages = {1076-7; author reply 1077-9}, doi = {10.1111/j.1464-5491.2009.02813.x}, pmid = {19900244}, issn = {1464-5491}, mesh = {Adult ; Diabetes Mellitus, Type 1/*psychology ; Diabetes Mellitus, Type 2/*psychology ; Humans ; Quality of Life/*psychology ; Research Design/*standards ; Surveys and Questionnaires/*standards ; }, } @article {pmid19897810, year = {2009}, author = {Bueno, S and Megherbi, H}, title = {French categorization norms for 70 semantic categories and comparison with Van Overschelde et al.'s (2004) English norms.}, journal = {Behavior research methods}, volume = {41}, number = {4}, pages = {1018-1028}, doi = {10.3758/BRM.41.4.1018}, pmid = {19897810}, issn = {1554-3528}, mesh = {Cross-Cultural Comparison ; England ; Female ; France ; Humans ; Language ; Linguistics ; Male ; Memory/physiology ; Psycholinguistics/*standards ; Reference Values ; Semantics ; Young Adult ; }, abstract = {The present methodological note provides categorization norms for 70 semantic categories collected from 200 participants. The categories were mainly derived from a French translation of the Van Overschelde, Rawson, and Dunlosky (2004) inductor terms including a large set of semantic categories. Our study also extends recent French norms (Léger, Boumlak, & Tijus, 2008; Marchal & Nicolas, 2003) and tests their stability. These 70 categories constitute the widest French categorization norms to date and will be of use to studies in the fields of both linguistics and psycholinguistics. A cross-linguistic comparison, with both quantitative and qualitative results, is also performed, which should prove useful for bilingual and/or cross-linguistic studies. The norms collected for all 70 categories are available for download as supplemental materials from http://brm.psychonomic-journals.org/content/supplemental.}, } @article {pmid19891853, year = {2009}, author = {Maniatis, LM}, title = {Comment on 'angle illusion on a picture's surface' by Hammad et al. (2008).}, journal = {Spatial vision}, volume = {22}, number = {6}, pages = {555-558}, doi = {10.1163/156856809789822952}, pmid = {19891853}, issn = {0169-1015}, mesh = {Form Perception/*physiology ; Humans ; Illusions/*physiology ; Paintings ; Pattern Recognition, Visual/*physiology ; }, abstract = {Hammad et al.'s (2008) conclusions as to the basis of angle illusions on a picture's surface are not justified by their data, which cannot in principle differentiate between their proposal and the proposed alternatives.}, } @article {pmid19882438, year = {2009}, author = {Tse, CS}, title = {The role of associative strength in the semantic relatedness effect on immediate serial recall.}, journal = {Memory (Hove, England)}, volume = {17}, number = {8}, pages = {874-891}, doi = {10.1080/09658210903376250}, pmid = {19882438}, issn = {1464-0686}, mesh = {Analysis of Variance ; Association Learning/*physiology ; Female ; Humans ; Male ; Memory, Short-Term/*physiology ; Mental Recall/*physiology ; Reaction Time ; Regression Analysis ; Semantics ; Serial Learning/*physiology ; Task Performance and Analysis ; User-Computer Interface ; Young Adult ; }, abstract = {The present study examined the effect of semantic relatedness on immediate serial recall. The type of semantic relatedness was manipulated by using lists of study items that are or are not from the same category (e.g., apple, banana, grape), and/or lists of study items that are or are not associated with each other (e.g., honey, sugar, sour). Whether the type of semantic relatedness was manipulated within or between participants, positive categorical and associative relatedness effects occurred in percent serial recall and negative categorical and associative relatedness effects occurred in order retention after the level of item recall was controlled. The R parameters, which were estimated by fitting Schweickert's (1993) multinomial processing tree model to the percent serial recall data, indicated a positive semantic relatedness effect on item redintegration. Regression analyses further showed that inter-item associative strength significantly predicts the percent serial recall after partialling out the effect of types of semantic relatedness or theme-item associative strength. Both Hulme et al.'s (1997) item redintegration theory and Stuart and Hulme's (2000) associative-link hypothesis are discussed.}, } @article {pmid19882238, year = {2011}, author = {Delgado, MY and Updegraff, KA and Roosa, MW and Umaña-Taylor, AJ}, title = {Discrimination and Mexican-origin adolescents' adjustment: the moderating roles of adolescents', mothers', and fathers' cultural orientations and values.}, journal = {Journal of youth and adolescence}, volume = {40}, number = {2}, pages = {125-139}, pmid = {19882238}, issn = {1573-6601}, support = {R01 HD039666/HD/NICHD NIH HHS/United States ; R01HD39666/HD/NICHD NIH HHS/United States ; }, mesh = {*Acculturation ; Adaptation, Psychological ; Adolescent ; Adolescent Behavior/*ethnology/psychology ; Adult ; *Cultural Characteristics ; Female ; Humans ; Interpersonal Relations ; Male ; Mexican Americans/psychology/*statistics & numerical data ; Middle Aged ; Parent-Child Relations/*ethnology ; Peer Group ; *Prejudice ; Social Adjustment ; Social Values/ethnology ; Socioeconomic Factors ; United States/epidemiology ; }, abstract = {Drawing on García Coll et al.'s integrative framework and the risk and resilience model, this study examined the relationships between adolescents' perceived discrimination and psychosocial adjustment and the moderating roles of adolescents', mothers', and fathers' cultural orientations and values, and adolescent gender in a sample of 246 Mexican-origin families. Using multilevel modeling with data from mothers, fathers, seventh graders (M (age) = 12.8 years; SD = .57 year) and older siblings (M (age) = 15.7 years; SD = 1.5 years), findings revealed that perceived discrimination was positively related to depression, risky behaviors, and deviant peer affiliations. In addition, parents' cultural orientations and values and adolescent gender moderated the relationships between perceived discrimination and some indicators of adjustment. These findings suggest that parents' cultural orientations and values can serve as protective and vulnerability factors in the associations between Mexican-origin adolescents' perceived discrimination and their psychosocial adjustment.}, } @article {pmid19857023, year = {2009}, author = {Lewandowsky, S and Oberauer, K}, title = {No evidence for temporal decay in working memory.}, journal = {Journal of experimental psychology. Learning, memory, and cognition}, volume = {35}, number = {6}, pages = {1545-1551}, doi = {10.1037/a0017010}, pmid = {19857023}, issn = {1939-1285}, mesh = {Humans ; Memory, Short-Term/*physiology ; Neuropsychological Tests ; Photic Stimulation/methods ; Reaction Time/physiology ; Time Factors ; *Time Perception ; }, abstract = {What drives forgetting in working memory? Recent evidence suggests that in a complex-span task in which an irrelevant processing task alternates with presentation of the memoranda, recall declines when the time taken to complete the processing task is extended while holding the time for rehearsal in between processing steps constant (Portrat, Barrouillet, & Camos, 2008). This time-based forgetting was interpreted in support for the role of time-based decay in working memory. In this article, we argue the contrary position by (a) showing in an experiment that the processing task in Portrat et al.'s (2008) study gave rise to uncontrolled post-error processes that occupied the attentional bottleneck, thus preventing restorative rehearsal, and (b) showing that when those post-error processes are statistically controlled, there is no evidence for temporal decay in Portrat et al.'s study. We conclude that currently there exists no direct evidence for temporal decay in the complex-span paradigm.}, } @article {pmid19857018, year = {2009}, author = {Butler, AC and Kang, SH and Roediger, HL}, title = {Congruity effects between materials and processing tasks in the survival processing paradigm.}, journal = {Journal of experimental psychology. Learning, memory, and cognition}, volume = {35}, number = {6}, pages = {1477-1486}, doi = {10.1037/a0017024}, pmid = {19857018}, issn = {1939-1285}, mesh = {Analysis of Variance ; Humans ; Mental Recall/*physiology ; Neuropsychological Tests ; Pattern Recognition, Visual ; Random Allocation ; Reaction Time/physiology ; Retention, Psychology/*physiology ; *Semantics ; Vocabulary ; }, abstract = {Nairne, Thompson, and Pandeirada (2007) reported a series of experiments in which processing unrelated words in terms of their relevance to a grasslands survival scenario led to better retention relative to other semantic processing tasks. The impetus for their study was the premise that human memory systems evolved under the selection pressures of our ancestral past. In 3 experiments, we extended this functional approach to investigate the congruity effect-the common finding that people remember items better if those items are congruent with the way in which they are processed. Experiment 1 was a replication of Nairne et al.'s (2007) experiment and showed congruity effects in the survival processing paradigm. To avoid potential item-selection artifacts from randomly selected words, we manipulated congruence between words and processing condition in Experiments 2 and 3. As expected, final recall was highest when the type of processing and the materials were congruent, indicating that people remember stimuli better if the stimuli are congruent with the goals associated with their processing. However, contrary to our predictions, no survival processing advantage emerged between the 2 congruent conditions or for a list of irrelevant words. When congruity was controlled in a mixed list design, the survival processing advantage disappeared.}, } @article {pmid19853718, year = {2009}, author = {Combaluzier, S and Gouvernet, B and Bernoussi, A}, title = {[Impact of personality disorders in a sample of 212 homeless drug users].}, journal = {L'Encephale}, volume = {35}, number = {5}, pages = {448-453}, doi = {10.1016/j.encep.2008.06.009}, pmid = {19853718}, issn = {0013-7006}, mesh = {Adult ; Comorbidity ; Cross-Sectional Studies ; Female ; Ill-Housed Persons/*psychology/*statistics & numerical data ; Humans ; Male ; Personality Disorders/*epidemiology/*psychology ; Risk Factors ; Statistics as Topic ; Substance-Related Disorders/*epidemiology/*psychology ; }, abstract = {INTRODUCTION: The impact of the mental disorders (axis I and II, according to DSM IV) on psychosocial problems (axis IV) is now a well-known fact, notably when substance abuse disorders are encountered on axis I. This leads to the conclusion that personality disorders increase the risk of substance abuse, that substance abuse increases the risk of homelessness, that dual diagnosis has a high impact on homelessness and underlines interactions between personality disorders (PD), drug abuse (DA) and homelessness. The aim of this paper is also to study these interactions.

METHOD: We will process the classical epidemiological measures, which have already produced interesting findings on other substance-linked disorders. We will study the multiplicative interaction (I(AB)) and the etiological fraction (EFi) linked to interaction, which evaluate the effects of two factors on another. According to the authors, the I(AB) determines whether the co-occurrence of two risk factors in a group induces more cases than each factor acting together; also if the I(AB) is greater than 1 it is possible to estimate the EFi, that proportionally measures the number of cases of the third factor that can be attributed to the co-occurrence. We will also study the interactions of homelessness and PD on DA, of the PD and DA on homelessness, and of this association DA and homelessness on PD. The data we will use in the paper deal with the prevalence of PD in general, drug users (n=226), homeless (n=999) and homeless drug abusers (n=212). The two last data are extracted from the same population and have been collected through clinical interviews, and the diagnosis follows the DSM criteria. They are comparable to Kokkevi et al.'s sample regarding the drug (heroin), the mean age (28 years for Kokkevi et al., 27 years in our sample), and the geographic origin of the populations (Mediterranean basin).

RESULTS: The repartition of PD differs significantly (0.001) in the homeless population and the homeless drug abusers (chi(2)=70.5, df=20). Therefore, the intensity of this link is low (rphi=0.30), which is a consequence of the high prevalence of PD in the homeless population (80% versus 10% in general population). On the other hand, the reparation of PD in the homeless drug abusers sample and Kokkevi et al.'s drug abusers is different at 0.001 (chi(2)=92.64, df=20). The link is high (rphi=0.45) and could be interpreted as a supplementary effect of PD's linked to homelessness and in the PD linked to DA, thus motivating further exploration of the interactions. The comorbidity DA/PD multiplies by 7 the risk of homelessness and explains 46% of the cases of homelessness of our sample (n=212). According to table 4, the association PD/homelessness multiplies by 13 the risk of DA and explains three-quarter of the cases of DA in the personality-disordered homeless people. Moreover, PD appear as basic in the etiopathology of such a morbid constellation since the frequency of their observation is independent of the association homelessness/DA. These findings rejoin the outcomes of similar studies on other addictions.

DISCUSSION: It could be objected that our sample of homeless men presents a high prevalence (20%) of DA; therefore agreeing with epidemiological works on the homeless population. The results could be discussed regarding other outcomes in drug abuser populations, in which a higher prevalence of PD has been found. Hence, the main results concerning interactions would not change and would have still led to the conclusion that PD are not influenced by the association homelessness/DA. This does not mean that neither homelessness nor DA have an impact on PD. Indeed, some authors have shown that there are variations in drug users' PD or in the neuropsychological effects of drugs. According to this and to the theory of a central role of PD in substance abuse, PD could influence drug use and be increased by the abuse. This hypothesis should be tested in another study.

CONCLUSION: Clinically, the association between DA and PD in homeless populations is a major concern regarding the future of these persons. This paper leads to the conclusion that the association PD/homelessness is a risk factor for DA, as is the dual diagnosis PD/DA for homelessness. In other words, in the case of PD, the DA increases the risk of homelessness, which is a risk factor for DA. Lastly, these findings confirm the interest of therapeutic approaches focused on PD.}, } @article {pmid19839696, year = {2009}, author = {Botvinick, MM and Plaut, DC}, title = {Empirical and computational support for context-dependent representations of serial order: reply to Bowers, Damian, and Davis (2009).}, journal = {Psychological review}, volume = {116}, number = {4}, pages = {998-1002}, doi = {10.1037/a0017113}, pmid = {19839696}, issn = {0033-295X}, mesh = {Association Learning ; Attention ; *Cognition ; Generalization, Psychological ; Humans ; *Memory, Short-Term ; *Neural Networks, Computer ; Retention, Psychology ; *Serial Learning ; }, abstract = {J. S. Bowers, M. F. Damian, and C. J. Davis critiqued the computational model of serial order memory put forth in M. Botvinick and D. C. Plaut, purporting to show that the model does not generalize in a way that people do. They attributed this supposed failure to the model's dependence on context-dependent representations, translating this argument into a general critique of all parallel distributed processing models. The authors reply here, addressing both Bowers et al.'s criticisms of the Botvinick and Plaut model and the former's assessment of parallel distributed processing models in general.}, } @article {pmid19838905, year = {2009}, author = {Lenny, P and Dear, GE}, title = {Faking good on the MCMI-III: implications for child custody evaluations.}, journal = {Journal of personality assessment}, volume = {91}, number = {6}, pages = {553-559}, doi = {10.1080/00223890903228505}, pmid = {19838905}, issn = {1532-7752}, mesh = {Adolescent ; Adult ; Australia ; *Child Custody ; *Deception ; Female ; Humans ; Male ; Middle Aged ; Parents/*psychology ; Personality Assessment/*standards ; Surveys and Questionnaires/*standards ; Young Adult ; }, abstract = {Individuals administered the MCMI-III (Millon, Davis, & Millon, 1997) as part of a custody evaluation have shown elevations on the Desirability (Y), Histrionic (4), Narcissistic (5), and Compulsive (7) scales and low scores on the Debasement (Z) scale (McCann et al., 2001) and all other personality and clinical scales. In this experiment, we instructed participants (N = 138) to look like good parents (fake good) or to answer honestly. The fake-good group scored higher than the honest group on Y, 4, 5, and 7 and lower on scale Z and most other scales. We plotted the mean scale scores of our fake-good group against those of McCann et al.'s custody litigants and found the 2 profiles to be very closely matched and very different from our answer-honestly group's profile. These findings raise the possibility that scale elevations on 4, 5, and 7 by custody litigants are artifacts of faking good rather than pathology in those areas. Assessors should interpret this profile cautiously in custody evaluations.}, } @article {pmid19838903, year = {2009}, author = {Bornstein, RF and Porcerelli, JH and Huprich, SK and Markova, T}, title = {Construct validity of the relationship profile test: correlates of overdependence, detachment, and healthy dependency in low income urban women seeking medical services.}, journal = {Journal of personality assessment}, volume = {91}, number = {6}, pages = {537-544}, doi = {10.1080/00223890903228406}, pmid = {19838903}, issn = {1532-7752}, mesh = {Adolescent ; Adult ; *Dependency, Psychological ; *Family Relations ; Female ; Humans ; *Interpersonal Relations ; Middle Aged ; Midwestern United States ; *Object Attachment ; *Patient Acceptance of Health Care ; Personality Assessment/*standards ; *Urban Population ; Young Adult ; }, abstract = {Studies have documented the construct validity of Bornstein and Languirand's (2003) Relationship Profile Test (RPT) in college students, psychotherapy patients, and nursing home residents, but no studies have examined the utility of RPT Destructive Overdependence (DO), Dysfunctional Detachment (DD), and Healthy Dependency (HD) scores in community samples. To fill this gap, we assessed links between RPT scores and theoretically related variables in low income urban women seeking medical services (N = 110), obtaining predicted links between RPT scores and scores on measures of childhood abuse and neglect, adult attachment style, conflict-resolution tactics involving a domestic partner, Axis I symptomatology, and overall quality of life. Comparison of RPT means in this sample with those in Bornstein et al.'s (2003) college student sample yielded differences that were generally in line with expectations. These results support the construct validity of RPT scores in urban women and suggest that the RPT may be a useful index of DO, DD, and HD in this heretofore unexamined population.}, } @article {pmid19833449, year = {2009}, author = {Lindenhovius, A and Karanicolas, PJ and Bhandari, M and van Dijk, N and Ring, D and , }, title = {Interobserver reliability of coronoid fracture classification: two-dimensional versus three-dimensional computed tomography.}, journal = {The Journal of hand surgery}, volume = {34}, number = {9}, pages = {1640-1646}, doi = {10.1016/j.jhsa.2009.07.009}, pmid = {19833449}, issn = {1531-6564}, mesh = {Humans ; *Imaging, Three-Dimensional ; Observer Variation ; *Tomography, X-Ray Computed ; Ulna Fractures/classification/*diagnostic imaging ; }, abstract = {PURPOSE: This study tests the hypothesis that 3-dimensional computed tomography (CT) reconstructions improve interobserver agreement on classification and treatment of coronoid fractures compared with 2-dimensional CT.

METHODS: A total of 29 orthopedic surgeons evaluated 10 coronoid fractures on 2 occasions (first with radiographs and 2-dimensional CT and then with radiographs and 3-dimensional CT), separated by a minimum of 2 weeks. Surgeons classified fractures according to the classifications of Regan and Morrey and of O'Driscoll et al., identified specific characteristics, recommended the most appropriate treatment approach, and made treatment recommendations. The kappa multirater measure (kappa) was calculated to estimate agreement between observers.

RESULTS: Regardless of the imaging modality used, there was fair to moderate agreement for most of the observations. Three-dimensional CT improved interobserver agreement in Regan and Morrey's classsication (kappa(3-dimensional) = 0.51 vs kappa(2-dimensional) = 0.40; p < .001) and O'Driscoll et al.'s classifications (kappa(3-dimensional) = 0.48 vs kappa(2-dimensional) = 0.42; p = .009). There were trends toward better reliability for 3-dimensional reconstruction in recognition of coronoid tip fractures (kappa(3-dimensional) = 0.19, kappa(2-dimensional) = 0.03; p = .268), comminution (kappa(3-dimensional) = 0.41 vs kappa(2-dimensional) = 0.29; p = .133), and impacted fragments (kappa(3-dimensional) = 0.39 vs kappa(2-dimensional) = 0.27; p = .094), and in surgeons' opinions on the need for something other than screws or plate for surgical fixation (kappa(3-dimensional) = 0.31 vs kappa(2-dimensional) = 0.15; p = .138). Interobserver agreement on treatment approach was better with 2-dimensional CT (kappa(3-dimensional) = 0.27, kappa(2-dimensional) = 0.32; p = .015).

CONCLUSIONS: Three-dimensional CT reconstructions improve interobserver agreement with respect to fracture classification compared with 2-dimensional CT.

Diagnostic III.}, } @article {pmid19797541, year = {2010}, author = {Catalani, C and Minkler, M}, title = {Photovoice: a review of the literature in health and public health.}, journal = {Health education & behavior : the official publication of the Society for Public Health Education}, volume = {37}, number = {3}, pages = {424-451}, doi = {10.1177/1090198109342084}, pmid = {19797541}, issn = {1552-6127}, mesh = {*Community Health Services ; Community Participation ; *Community-Based Participatory Research ; *Health Education ; Health Policy ; Health Promotion ; Humans ; Outcome and Process Assessment, Health Care ; Photography ; *Public Health ; }, abstract = {Although a growing number of projects have been implemented using the community-based participatory research method known as photovoice, no known systematic review of the literature on this approach has been conducted to date. This review draws on the peer-reviewed literature on photovoice in public health and related disciplines conducted before January 2008 to determine (a) what defines the photovoice process, (b) the outcomes associated with photovoice, and (c) how the level of community participation is related to photovoice processes and outcomes. In all, 37 unduplicated articles were identified and reviewed using a descriptive coding scheme and Viswanathan et al.'s quality of participation tool. Findings reveal no relationship between group size and quality of participation but a direct relationship between the latter and project duration as well as with getting to action. More participatory projects also were associated with long-standing relationships between the community and outside researcher partners and an intensive training component. Although vague descriptions of project evaluation practices and a lack of consistent reporting precluded hard conclusions, 60% of projects reported an action component. Particularly among highly participatory projects, photovoice appears to contribute to an enhanced understanding of community assets and needs and to empowerment.}, } @article {pmid19789957, year = {2009}, author = {Magnavita, N and Fileni, A and Bergamaschi, A}, title = {Satisfaction at work among radiologists.}, journal = {La Radiologia medica}, volume = {114}, number = {8}, pages = {1330-1344}, pmid = {19789957}, issn = {1826-6983}, mesh = {Adult ; *Attitude of Health Personnel ; Case-Control Studies ; Female ; Humans ; Italy/epidemiology ; *Job Satisfaction ; Logistic Models ; Male ; Middle Aged ; Physicians/*psychology/*statistics & numerical data ; Physicians, Women/psychology/statistics & numerical data ; Pilot Projects ; Radiology/*statistics & numerical data ; Regression Analysis ; Stress, Psychological/epidemiology/etiology ; Surveys and Questionnaires ; Workload/psychology ; }, abstract = {PURPOSE: This study sought to evaluate professional satisfaction among Italian radiologists and identify what personal characteristics of radiologists and features of their work and work setting affect job satisfaction.

MATERIALS AND METHODS: Satisfaction was assessed by using Warr et al.'s 17-item Job Satisfaction Scale (JSS) in 206 radiologists, 108 radiotherapists and 34 specialists in infectious diseases used as controls.

RESULTS: Forty-nine per cent of diagnostic radiologists reported being satisfied with their jobs. The frequency is significantly lower than that found among radiotherapists (64%) and controls (62%). Middle-aged radiologists on lower rungs of the career ladder were more dissatisfied than were their older colleagues in top positions. Female radiologists were less satisfied than their male counterparts with regard to recognition for good work, amount of job variety and distribution of workloads. Stepwise logistic regression analysis showed that job satisfaction was especially affected by physical working conditions, freedom to choose one's own work method, relationship with one's immediate boss, attention paid to one's suggestions and the amount of job variety.

CONCLUSIONS: This pilot study identified the sources of professional satisfaction and dissatisfaction among radiologists. A future survey of a stratified random sample of Italian radiologists appears to be feasible.}, } @article {pmid19788774, year = {2009}, author = {Mullane, M and Dooley, B and Tiernan, E and Bates, U}, title = {Validation of the Demoralization Scale in an Irish advanced cancer sample.}, journal = {Palliative & supportive care}, volume = {7}, number = {3}, pages = {323-330}, doi = {10.1017/S1478951509990253}, pmid = {19788774}, issn = {1478-9523}, mesh = {*Adaptation, Psychological ; Aged ; *Cross-Cultural Comparison ; Depressive Disorder/diagnosis/psychology ; Female ; Humans ; Ireland ; Male ; Middle Aged ; *Motivation ; Neoplasm Staging ; Neoplasms/pathology/*psychology ; Palliative Care/*psychology ; Personality Inventory/*statistics & numerical data ; Principal Component Analysis ; Psychometrics/statistics & numerical data ; Quality of Life/psychology ; Reproducibility of Results ; }, abstract = {OBJECTIVE: This article presents a validation study of the Demoralization Scale, a 24-item, 5-point response questionnaire developed by Kissane et al. in 2004 to assess demoralization in advanced cancer patients.

METHOD: One hundred Irish inpatients with advanced palliative cancer completed the Demoralization Scale and measures of depression, hopelessness, quality of life, and personal hopefulness.

RESULTS: Principal component analysis of the Demoralization Scale yielded four similar factors found by Kissane et al. (2004), namely, loss of meaning, dysphoria, disheartenment, and sense of failure. A new factor, the hopelessness factor, was also found in the current study. The reliability of the five factors was good, ranging from .72 to .93. Contrary to the findings of Kissane et al.'s (2004) study, divergent validity of the Demoralization Scale was not supported. Demoralized patients were significantly more likely to be depressed than those that did not score highly on the Demoralization Scale. In addition, this study found significantly lower levels of demoralization in general compared with Kissane et al.'s (2004) study.

SIGNIFICANCE OF RESULTS: The results of the current study show that, in an Irish palliative care context, demoralization is not differentiated from depression. Additional factor analytic studies are needed to validate the Demoralization Scale.}, } @article {pmid19782365, year = {2010}, author = {Nordez, A and Fouré, A and Dombroski, EW and Mariot, JP and Cornu, C and McNair, PJ}, title = {Improvements to Hoang et al.'s method for measuring passive length-tension properties of human gastrocnemius muscle in vivo.}, journal = {Journal of biomechanics}, volume = {43}, number = {2}, pages = {379-382}, doi = {10.1016/j.jbiomech.2009.07.034}, pmid = {19782365}, issn = {1873-2380}, mesh = {Adult ; Biomechanical Phenomena ; Elasticity ; Humans ; Knee Joint/physiology ; Male ; *Models, Biological ; Muscle Contraction/physiology ; Muscle, Skeletal/*physiology ; Tendons/physiology ; Torque ; Young Adult ; }, abstract = {While the passive mechanical properties of a musculo-articular complex can be determined using the relationship between the articular angle and the passive torque developed in resistance to motion, the properties of different structures of the musculo-articular complex cannot be easily assessed. Recently, an elegant method has been proposed to estimate the passive length-tension properties of gastrocnemius muscle-tendon unit (Hoang et al., 2005). In the present paper, two improvements of this method are proposed to decrease the number of parameters required to assess the passive length-tension relationship from 9 to 2. Furthermore, these two parameters have physical meaning as they represent a passive muscle-tendon stiffness index (alpha) and the muscle-tendon slack length (l(0)). alpha and l(0) are relevant clinical parameters to study the chronic effects of aging, training protocols or neuromuscular pathologies on the passive mechanical properties of the muscle-tendon unit. Eight healthy subjects performed passive loading/unloading cycles at 5 degrees /s with knee angle at 6 knee angles to assess the torque-angle relationships and to apply the modified method. Numerical optimization was used to minimize the squared error between the experimental and the modeled relationships. The experiment was performed twice to assess the reliability of alpha and l(0) across days. The results showed that the reliability of the two parameters was good (alpha: ICC=0.82, SEM=6.1m(-1), CV=6.3% and l(0): ICC=0.83, SEM=0.29 cm, CV=0.9%). Using a sensitivity analysis, it was shown that the numerical solution was unique. Overall, the findings may provide increased interest in the method proposed by Hoang et al. (2005).}, } @article {pmid19748375, year = {2009}, author = {Le Bec, PY and Fatséas, M and Denis, C and Lavie, E and Auriacombe, M}, title = {[Cannabis and psychosis: search of a causal link through a critical and systematic review].}, journal = {L'Encephale}, volume = {35}, number = {4}, pages = {377-385}, doi = {10.1016/j.encep.2008.02.012}, pmid = {19748375}, issn = {0013-7006}, mesh = {Cannabinoids/*toxicity ; Causality ; Chronic Disease ; Cohort Studies ; Comorbidity ; Dose-Response Relationship, Drug ; Humans ; Marijuana Abuse/*epidemiology ; Prospective Studies ; Psychoses, Substance-Induced/*epidemiology/*etiology ; Risk Factors ; }, abstract = {INTRODUCTION: Although cannabis use may be involved in the aetiology of acute psychosis, there has been considerable debate about the association observed between cannabis use and chronic psychosis. In particular, because of the frequent co-occurrence between schizophrenia and cannabis use, the question has been raised of a causal link between exposure to cannabis as a risk factor and the development of psychosis or psychotic symptoms.

OBJECTIVE: The aim of this article was to examine the evidence that cannabis use causes chronic psychotic disorders by using established criteria of causality. These criteria were defined by: biologic plausibility, strength of the interaction between the risk factor and the disease, reprieability of the results, temporal sequence between the exposure to the risk factor and the beginning of the disease and existence of a dose-effect relationship.

METHODS: The selected studies were found in Medline using the keywords "cannabis" and "psychosis", "cannabis" and "schizophrenia", "cannabis" and "psychotic symptoms" and "prospective" or "cohort" or "longitudinal". The selected studies were all prospective studies assessing the temporal sequence between cannabis use and emergence of psychosis or psychotic symptoms. The search strategies resulted in 60 records that were screened by reading both titles and abstracts. Seventeen studies were considered eligible, and then, after reading the full text, seven met the inclusion criteria.

RESULTS: Together, the seven studies were all prospective cohorts and represented 50,275 human subjects. There were three European studies (from Sweden, Holland and Germany), one from New Zealand and one from Australia. Only one study of the seven did not show a significant association between cannabis consumption and increase of the risk of developing a psychosis. However, this study had some bias, such as low level of cannabis use and the lack of evaluation of cannabis use after inclusion. For the six other studies, data show the existence of a significant association between cannabis use and psychotic disorders (with an increased risk between 1.2 and 2.8 in Zammit et al.'s study), particularly among vulnerable individuals (that is with a prepsychotic state at the time of inclusion). Therefore, all the studies that assessed a dose-effect relationship showed this link between cannabis use and the emergence of psychosis or psychotic symptoms. The fact that all causal criteria were present in the studies suggests that cannabis use may be an independent risk factor for the development of psychosis. Results seem to be more consistent for vulnerable individuals with the hypothesis that cannabis use may precipitate psychosis, notably among vulnerable subjects. In particular, early onset of cannabis use during adolescence should be an environmental stressor that interacts with a genetic predisposition to induce a psychotic disorder.

CONCLUSION: The objective of this article was to examine whether cannabis use can be an independent risk factor for chronic psychotic disorders, by using established criteria of causality. Data extracted from the selected studies showed that cannabis use may be an independent risk factor for the development of psychotic disorders. Early screening of the vulnerability to psychotic disorder should permit improved focus on prevention and information about the specific risks related to cannabis use among this population.}, } @article {pmid19732012, year = {2009}, author = {Van Nostrand, D and Atkins, F and Moreau, S and Aiken, M and Kulkarni, K and Wu, JS and Burman, KD and Wartofsky, L}, title = {Utility of the radioiodine whole-body retention at 48 hours for modifying empiric activity of 131-iodine for the treatment of metastatic well-differentiated thyroid carcinoma.}, journal = {Thyroid : official journal of the American Thyroid Association}, volume = {19}, number = {10}, pages = {1093-1098}, doi = {10.1089/thy.2008.0339}, pmid = {19732012}, issn = {1557-9077}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Combined Modality Therapy ; Female ; Humans ; Iodine Radioisotopes/*pharmacokinetics/*therapeutic use ; Male ; Middle Aged ; Neoplasm Metastasis ; Radiometry ; Retrospective Studies ; Thyroid Neoplasms/*pathology/*radiotherapy ; Thyroidectomy ; Young Adult ; }, abstract = {BACKGROUND: Dosimetry has been used to help identify when empiric dosages of 131-I treatment for suspected metastatic well-differentiated thyroid carcinoma (WDTC) may be increased or should be decreased, but dosimetry is complex, and easier approaches would be useful. The three objectives of this study were to assess the utility of the percent whole-body retention of 131-I at 48 hours (%WBR(48hr)) in identifying patients with WDTC in whom the therapeutic empiric prescribed activity of 131-I might be increased/decreased, to evaluate the thresholds proposed by Sisson et al. in 2003 for increasing or decreasing activity, and to determine the relationship between %WBR(48hr) and maximum tolerated activity (MTA).

METHOD: A retrospective review was conducted of patients who had WDTC, total thyroidectomy, suspected metastatic disease, thyroid hormone withdrawal, and 131-I dosimetry. The %WBR(48hr) was determined based on the Benua-Leeper dosimetry protocol, and the four thresholds and recommendations of Sisson et al., 2003 for the use of %WBR(48hr) were evaluated relative to an empiric activity (EA) of 7.4 GBq of 131-I. A biexponential equation was determined from the %WBR(48hr) data.

RESULTS: Of 142 patients, 47 patients had a %WBR(48hr) of <9%, and all could have received more than the EA of 7.4 GBq with an average of 21.0 GBq (incremental range of 6.8-23.2 GBq). Ten patients had a %WBR(48hr) < or = 5%, and all could have had their EA of 7.4 GBq safely increased by at least 250%. Conversely, if the %WBR(48hr) was >24.8%, then 7 of 14 of these patients would have exceeded the MTA by 0.37-3.18 GBq with an EA of 7.4 GBq. Finally, for patients with a %WBR(48hr) > 40%, five of six patients would have exceeded the MTA by 0.85-3.18 GBq. A biexponential regression equation is presented.

CONCLUSION: We conclude that, with respect to the treatment of metastatic epithelial cell thyroid cancer, the %WBR(48hr) of 131-I helps identify those patients in whom the empiric therapeutic prescribed activity of 131-I may be increased or should be decreased so as not to exceed the MTA and that Sisson et al.'s thresholds published in 2003 are applicable. We favor a biexponential regression model using the %WBR(48hr) and a lower limit threshold as a potentially useful method for determining how much an empiric therapeutic prescribed activity of 131-I can be increased or decreased.}, } @article {pmid19719722, year = {2009}, author = {Bradley, C}, title = {Psychometric tools for measuring outcomes of diabetes education; a critique of Eigenmann et al.'s assessment of suitability.}, journal = {Diabetic medicine : a journal of the British Diabetic Association}, volume = {26}, number = {9}, pages = {952-953}, doi = {10.1111/j.1464-5491.2009.02793.x}, pmid = {19719722}, issn = {1464-5491}, mesh = {Diabetes Mellitus/*psychology ; Humans ; Patient Education as Topic ; Psychometrics/methods ; United Kingdom ; }, } @article {pmid19712936, year = {2009}, author = {Chang, CC and Yang, RJ}, title = {A perspective on streaming current in silica nanofluidic channels: Poisson-Boltzmann model versus Poisson-Nernst-Planck model.}, journal = {Journal of colloid and interface science}, volume = {339}, number = {2}, pages = {517-520}, doi = {10.1016/j.jcis.2009.07.056}, pmid = {19712936}, issn = {1095-7103}, abstract = {Choi and Kim [J. Colloid Interface Sci. 333 (2009) 672] proposed a new wall boundary condition for zeta-potential and surface charge density to describe the electrokinetic flow-induced currents in silica nanofluidic channels using the Poisson-Boltzmann (PB) model and the Poisson-Nernst-Planck (PNP) model. They showed that the results from the PNP model are in close agreement with the experimental data reported by van der Heyden et al. [Phys. Rev. Lett. 95 (2005) 116104]. In this paper, a theoretical model based on the PB model incorporating their proposed boundary condition is presented, which does not necessitate highly expensive computational effort. The results from our proposed model are shown to be in agreement with their numerical results of the PNP model. The present model also addresses the importance of the electrical resistance of reservoirs or the position of the electrodes for the measurement of the streaming current. Further, we point out that there is a misinterpretation in a comparison between their numerical results and those of van der Heyden et al.'s experiments. Finally, we conclude that the experimental data still cannot be predicted accurately by their proposed boundary condition and model, especially for the electrolyte concentration C(0)<10(-3)M.}, } @article {pmid19702862, year = {2009}, author = {Santos, F and Teusink, B and de Vos, WM and Hugenholtz, J}, title = {The evidence that pseudovitamin B(12) is biologically active in mammals is still lacking - a comment on Molina et al.'s (2009) experimental design.}, journal = {Journal of applied microbiology}, volume = {107}, number = {5}, pages = {1763; author reply 1764}, doi = {10.1111/j.1365-2672.2009.04468.x}, pmid = {19702862}, issn = {1365-2672}, mesh = {Animals ; Culture Media ; Limosilactobacillus reuteri/*metabolism ; Mammals ; Mice ; Vitamin B 12/*analogs & derivatives/isolation & purification/*metabolism ; }, } @article {pmid19702363, year = {2009}, author = {Robbins, SB and Oh, IS and Le, H and Button, C}, title = {Intervention effects on college performance and retention as mediated by motivational, emotional, and social control factors: integrated meta-analytic path analyses.}, journal = {The Journal of applied psychology}, volume = {94}, number = {5}, pages = {1163-1184}, doi = {10.1037/a0015738}, pmid = {19702363}, issn = {0021-9010}, mesh = {*Educational Status ; Humans ; Models, Theoretical ; Motivation ; Psychology, Educational ; Social Control, Informal ; Socioeconomic Factors ; Student Dropouts/psychology ; Students/*psychology ; }, abstract = {Using both organizational and educational perspectives, the authors proposed and tested theoretical models on the mediating roles that psychosocial factors (PSFs; motivational, emotional, and social control factors) play between college interventions (academic skill, self-management, socialization, and First-Year-Experience interventions) and college outcomes (academic performance and retention). They first determined through meta-analysis of 404 data points the effects of college interventions on college outcomes and on PSFs. These meta-analytic findings were then combined with results from S. B. Robbins et al.'s (2004) meta-analysis to test the proposed models. Integrated meta-analytic path analyses showed the direct and indirect effects (via PSFs) of intervention strategies on both performance and retention outcomes. The authors highlight the importance of both academic skill and self-management-based interventions; they also note the salience of motivational and emotional control mediators across both performance and retention outcomes. Implications from organizational and educational perspectives, limitations, and future directions are addressed.}, } @article {pmid19687054, year = {2009}, author = {Abban, G and Johnson, J}, title = {Stem cell support of oogenesis in the human.}, journal = {Human reproduction (Oxford, England)}, volume = {24}, number = {12}, pages = {2974-2978}, doi = {10.1093/humrep/dep281}, pmid = {19687054}, issn = {1460-2350}, mesh = {Animals ; Cell Proliferation ; Cell Separation ; Female ; Germ Cells/*cytology/physiology ; Humans ; Mice ; Oocytes/cytology/*physiology ; *Oogenesis ; Ovary/cytology/*physiology ; Regeneration ; Stem Cell Transplantation/*methods ; Stem Cells/cytology/*physiology ; }, abstract = {The possibility that women produce new oocytes post-natally as part of the normal physiological function of the ovary is currently under investigation. Post-natal production of oocyte-like cells has been detected under experimental conditions in the mouse. Although these cells have many characteristics of oocytes, their potential to mature to fertilization-competence was unproven. Zou et al. (Production of offspring from a germline stem cell line derived from neonatal ovaries. Nat Cell Biol 2009;11:631-636) made use of a striking cell isolation and culture strategy to establish cultures of proliferative germ cells from both newborn and adult ovaries. Their cells, referred to as female germline stem cells (FGSCs), proliferate long-term in culture and accept and maintain expression of a transgenic marker, green fluorescent protein. When delivered to the ovaries of conditioned mice, transgene-bearing FGSC engrafted, were enclosed within follicles, and when host females were mated, transgenic offspring were produced. That proliferative female germ cells capable of giving rise to offspring were detected in adult ovaries poses the question of whether they have a physiological role. Here, we discuss Zou et al.'s data in terms of our current understanding of mouse ovarian physiology, and how this may relate to human reproductive biology and the treatment of ovarian dysfunction.}, } @article {pmid19680574, year = {2009}, author = {Price, CW and Leslie, DC and Landers, JP}, title = {Nucleic acid extraction techniques and application to the microchip.}, journal = {Lab on a chip}, volume = {9}, number = {17}, pages = {2484-2494}, doi = {10.1039/b907652m}, pmid = {19680574}, issn = {1473-0197}, mesh = {Nucleic Acids/*isolation & purification ; *Oligonucleotide Array Sequence Analysis ; }, abstract = {As recently as the early 1990s, DNA purification was time-consuming, requiring the use of toxic, hazardous reagents. The advent of solid phase extraction techniques and the availability of commercial kits for quick and reliable DNA extraction has relegated those early techniques largely to the history books. High quality DNA can now be extracted from whole blood, serum, saliva, urine, stool, cerebral spinal fluid, tissues, and cells in less time without sacrificing recovery. Having achieved such a radical change in the methodology of DNA extraction, focus has shifted to adapting these methods to a miniaturized system, or "lab-on-a-chip" (A. Manz, N. Graber and H. M. Widmer, Sens. Actuators, B, 1990, 1, 244-248). Manz et al.'s concept of a "miniaturized total chemical analysis system" (microTAS) involved a silicon chip that incorporated sample pretreatment, separation and detection. This review will focus on the first of these steps, sample pretreatment in the form of DNA purification. The intention of this review is to provide an overview of the fundamentals of nucleic acid purification and solid phase extraction (SPE) and to discuss specific microchip DNA extraction successes and challenges. In order to fully appreciate the advances in DNA purification, a brief review of the history of DNA extraction is provided so that the reader has an understanding of the impact that the development of SPE techniques have had. This review will highlight the different methods of nucleic acid extraction (Table 1), including relevant citations, but without an exhaustive summary of the literature. A recent review by Wen et al. (J. Wen, L. A. Legendre, J. M. Bienvenue and J. P. Landers, Anal. Chem., 2008, 80, 6472-6479) covers solid phase extraction methods with a greater focus on their incorporation into integrated microfluidic systems.}, } @article {pmid19675361, year = {2009}, author = {Grossman, SF}, title = {Commentary on Powers et al.'s article: "interpersonal violence and women with disabilities: an analysis of safety promoting behaviors".}, journal = {Violence against women}, volume = {15}, number = {9}, pages = {1070-4; discussion 1080-6}, doi = {10.1177/1077801209340310}, pmid = {19675361}, issn = {1077-8012}, mesh = {Adult ; Battered Women/*psychology/statistics & numerical data ; Persons with Disabilities/psychology/*statistics & numerical data ; Female ; Health Behavior ; Health Promotion/*methods ; Humans ; Interpersonal Relations ; Middle Aged ; Reproducibility of Results ; Sexual Partners ; Spouse Abuse/*prevention & control/statistics & numerical data ; *Surveys and Questionnaires ; *Women's Health ; Young Adult ; }, } @article {pmid19675359, year = {2009}, author = {Fisher, BS}, title = {Commentary on Curry et al.'s safer and stronger program and suggestions for future methodological research.}, journal = {Violence against women}, volume = {15}, number = {9}, pages = {1026-34; discussion 1080-6}, doi = {10.1177/1077801209340307}, pmid = {19675359}, issn = {1077-8012}, mesh = {Adult ; Battered Women/*psychology/statistics & numerical data ; Persons with Disabilities/psychology/*statistics & numerical data ; Female ; Humans ; Interpersonal Relations ; Middle Aged ; Reproducibility of Results ; *Self Concept ; Self Disclosure ; Sexual Partners ; Spouse Abuse/*diagnosis/*prevention & control/statistics & numerical data ; Surveys and Questionnaires ; *Women's Health ; Young Adult ; }, } @article {pmid19674060, year = {2009}, author = {Doss, RC and Zhang, W and Risse, GL and Dickens, DL}, title = {Lateralizing language with magnetic source imaging: validation based on the Wada test.}, journal = {Epilepsia}, volume = {50}, number = {10}, pages = {2242-2248}, doi = {10.1111/j.1528-1167.2009.02242.x}, pmid = {19674060}, issn = {1528-1167}, mesh = {Adolescent ; Adult ; Amobarbital/administration & dosage/pharmacology ; Brain/*physiopathology/surgery ; Brain Mapping/methods ; Brain Neoplasms/diagnosis/physiopathology/surgery ; Carotid Artery, Internal ; Cerebral Cortex/physiopathology ; Epilepsy/diagnosis/*physiopathology/surgery ; Female ; Functional Laterality/drug effects/*physiology ; Humans ; *Language ; Language Tests ; Magnetoencephalography/*statistics & numerical data ; Male ; Preoperative Care ; Reproducibility of Results ; Sensitivity and Specificity ; Verbal Behavior/drug effects ; }, abstract = {PURPOSE: Magnetoencephalography (MEG)/magnetic source imaging (MSI) is a noninvasive functional neuroimaging procedure used to localize language-specific regions in the brain. The Wada test, or intracarotid amobarbital procedure (IAP), is the gold standard in determining speech/language lateralization for presurgical planning, although it is invasive and associated with morbidity. The purpose of this study is to provide further validation on the use of MSI for presurgical language lateralization by comparing results against the IAP.

METHODS: The sample consisted of 35 patients with epilepsy and/or brain tumor undergoing presurgical evaluation at the Minnesota Epilepsy Group. All patients received both an IAP and MSI to determine hemispheric language dominance. For MSI, a 148-channel MEG system was used to record activation of language-specific cortex by an auditory word-recognition task.

RESULTS: The MSI and IAP were concordant in determining language in the hemisphere to be treated in 86% of the cases with sensitivity and specificity values of 80% and 100%, respectively.

CONCLUSIONS: The results from this study are consistent with prior research findings comparing functional neuroimaging procedures to the IAP in determining language lateralization in presurgical patients. The current study provides an important replication and support for Papanicolaou et al.'s findings in 2004 using a consecutive clinical sample from a different institution. An unusually high rate of atypical IAP language cases in this sample and differences between the two procedures are believed to explain the noted discrepancies. MSI is a viable noninvasive alternative to the IAP in the presurgical determination of language lateralization.}, } @article {pmid19666705, year = {2009}, author = {Dear, K}, title = {Commentary: On Hashizume et al.'s 'The effect of temperature on mortality in rural Bangladesh'.}, journal = {International journal of epidemiology}, volume = {38}, number = {6}, pages = {1697-1699}, doi = {10.1093/ije/dyp271}, pmid = {19666705}, issn = {1464-3685}, mesh = {Age Factors ; Bangladesh ; Cause of Death/trends ; Cold Temperature ; *Data Interpretation, Statistical ; Hot Temperature ; Humans ; Kidney Diseases/mortality ; Mortality/*trends ; }, } @article {pmid19662533, year = {2011}, author = {Schafer, RM and Handal, PJ and Brawer, PA and Ubinger, M}, title = {Training and education in religion/spirituality within APA-accredited clinical psychology programs: 8 years later.}, journal = {Journal of religion and health}, volume = {50}, number = {2}, pages = {232-239}, pmid = {19662533}, issn = {1573-6571}, mesh = {*Accreditation ; Data Collection ; *Education, Graduate ; Humans ; Psychology, Clinical/*education ; *Religion and Psychology ; *Societies, Scientific ; *Spirituality ; United States ; }, abstract = {This study was a follow up investigation of Brawer et al.'s (Prof Psychol Res Pr 33(2):203-206, 2002) survey of education and training of clinical psychologists in religion/spirituality. Directors of clinical training were surveyed to determine whether changes had occurred in the coverage of religion and spirituality through course work, research, supervision, and in the systematic coverage of the content area. Results indicated an increased coverage in the areas of supervision, dedicated courses, inclusion as part of another course, and research. There was no increase in systematic coverage, but significantly more programs provided at least some coverage. The current study also assesses other areas of incorporation as well as directors' opinions regarding the importance of religion/spirituality in the field of psychology.}, } @article {pmid19644552, year = {2009}, author = {Dresp-Langley, B and Durup, J}, title = {A plastic temporal brain code for conscious state generation.}, journal = {Neural plasticity}, volume = {2009}, number = {}, pages = {482696}, pmid = {19644552}, issn = {1687-5443}, mesh = {Action Potentials/*physiology ; Animals ; Brain/*physiology ; Computer Simulation ; Consciousness/*physiology ; Humans ; Models, Neurological ; Nerve Net/*physiology ; Neural Pathways/physiology ; Neuronal Plasticity/physiology ; Neurons/*physiology ; Nonlinear Dynamics ; Perception/physiology ; Sensation/physiology ; Synaptic Transmission/*physiology ; Time Factors ; Time Perception/physiology ; }, abstract = {Consciousness is known to be limited in processing capacity and often described in terms of a unique processing stream across a single dimension: time. In this paper, we discuss a purely temporal pattern code, functionally decoupled from spatial signals, for conscious state generation in the brain. Arguments in favour of such a code include Dehaene et al.'s long-distance reverberation postulate, Ramachandran's remapping hypothesis, evidence for a temporal coherence index and coincidence detectors, and Grossberg's Adaptive Resonance Theory. A time-bin resonance model is developed, where temporal signatures of conscious states are generated on the basis of signal reverberation across large distances in highly plastic neural circuits. The temporal signatures are delivered by neural activity patterns which, beyond a certain statistical threshold, activate, maintain, and terminate a conscious brain state like a bar code would activate, maintain, or inactivate the electronic locks of a safe. Such temporal resonance would reflect a higher level of neural processing, independent from sensorial or perceptual brain mechanisms.}, } @article {pmid19640625, year = {2009}, author = {Kreatsoulas, C and Anand, S}, title = {Considering race/ethnicity and socio-economic status in randomized controlled trials. A commentary on Frampton et al.'s systematic review generalizing trial findings and tackling health disparities in asthma research.}, journal = {Social science & medicine (1982)}, volume = {69}, number = {8}, pages = {1155-1156}, doi = {10.1016/j.socscimed.2009.06.019}, pmid = {19640625}, issn = {1873-5347}, mesh = {*Ethnicity ; Female ; Humans ; Male ; Racial Groups ; Randomized Controlled Trials as Topic/*standards ; Research Design/*standards ; *Selection Bias ; Social Class ; }, } @article {pmid19614739, year = {2009}, author = {Udoye, CI and Jafarzadeh, H}, title = {Dilaceration among Nigerians: prevalence, distribution, and its relationship with trauma.}, journal = {Dental traumatology : official publication of International Association for Dental Traumatology}, volume = {25}, number = {4}, pages = {439-441}, doi = {10.1111/j.1600-9657.2009.00796.x}, pmid = {19614739}, issn = {1600-9657}, mesh = {Adolescent ; Adult ; Age Factors ; Aged ; Bicuspid/abnormalities/injuries ; Female ; Humans ; Male ; Maxilla ; Middle Aged ; Molar/abnormalities/injuries ; Molar, Third/abnormalities/injuries ; Nigeria/epidemiology ; Prevalence ; Radiography, Bitewing/statistics & numerical data ; Retrospective Studies ; Sex Factors ; Tooth Injuries/*epidemiology ; Tooth Root/*abnormalities/injuries ; Young Adult ; }, abstract = {Dilaceration is the result of a developmental anomaly in which an abrupt change in the axial inclination between crown and root is observed. Its prevalence in various races is different and its association with history of trauma is controversial. This study assessed the prevalence and distribution of dilacerated teeth among Nigerians and also investigated whether there was a relation between a history of trauma and teeth that had dilaceration. A total of 465 records of adult attendees (involving 706 teeth and 256 films) were retrospectively studied. Dilacerated teeth were scored using Hamasha et al.'s criteria. Dilaceration occurred more often in the maxilla, posterior teeth and in women, though no association between a history of trauma and occurrence of dilaceration was found. Prevalence of dilaceration in the population and in all teeth was 4.5% and 2.97%, respectively. Dentists should pay detailed attention to baseline radiographs, especially in maxilla and posterior teeth.}, } @article {pmid19603827, year = {2009}, author = {Bern, M and Phinney, BS and Goldberg, D}, title = {Reanalysis of Tyrannosaurus rex Mass Spectra.}, journal = {Journal of proteome research}, volume = {8}, number = {9}, pages = {4328-4332}, pmid = {19603827}, issn = {1535-3893}, support = {R21 GM085718/GM/NIGMS NIH HHS/United States ; GM085718/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Collagen/chemistry ; Databases, Protein ; *Dinosaurs ; *Fossils ; Hemoglobins/chemistry ; Mass Spectrometry/*methods ; Peptides/analysis ; Proteomics/*methods ; }, abstract = {Asara et al. reported the detection of collagen peptides in a 68-million-year-old Tyrannosaurus rex bone by shotgun proteomics. This finding has been called into question as a possible statistical artifact. We reanalyze Asara et al.'s tandem mass spectra using a different search engine and different statistical tools. Our reanalysis shows a sample containing common laboratory contaminants, soil bacteria, and bird-like hemoglobin and collagen.}, } @article {pmid19589178, year = {2009}, author = {Chiang, YC and Hung, KH and Moore, SJ and Ge, XJ and Huang, S and Hsu, TW and Schaal, BA and Chiang, T}, title = {Paraphyly of organelle DNAs in Cycas Sect. Asiorientales due to ancient ancestral polymorphisms.}, journal = {BMC evolutionary biology}, volume = {9}, number = {}, pages = {161}, pmid = {19589178}, issn = {1471-2148}, mesh = {China ; Cycas/*genetics ; DNA, Chloroplast/*genetics ; DNA, Mitochondrial/*genetics ; DNA, Plant/genetics ; DNA, Ribosomal Spacer/genetics ; *Evolution, Molecular ; Genes, Plant ; Genetics, Population ; Geography ; Haplotypes ; Phylogeny ; *Polymorphism, Genetic ; Sequence Alignment ; Sequence Analysis, DNA ; }, abstract = {BACKGROUND: This study addresses the apportionment of genetic diversity between Cycas revoluta and C. taitungensis, species that constitute the section Asiorientales and represent a unique, basal lineage of the Laurasian genus Cycas. Fossil evidence indicates divergence of the section from the rest of Cycas at least 30 million years ago. Geographically, C. taitungensis is limited to Taiwan whereas C. revoluta is found in the Ryukyu Archipelago and on mainland China.

RESULTS: The phylogenies of ribosomal ITS region of mtDNA and the intergenic spacer between atpB and rbcL genes of cpDNA were reconstructed. Phylogenetic analyses revealed paraphyly of both loci in the two species and also in the section Asiorientales. The lack of reciprocal monophyly between these long isolated sections is likely due to persistent shared ancestral polymorphisms. Molecular dating estimated that mt- and cp DNA lineages coalesced to the most recent common ancestors (TMRCA) about 327 (mt) and 204 MYA (cp), corresponding with the divergence of cycad sections in the Mesozoic.

CONCLUSION: Fates of newly derived mutations of cycads follow Klopfstein et al.'s surfing model where the majority of new mutations do not spread geographically and remain at low frequencies or are eventually lost by genetic drift. Only successful 'surfing mutations' reach very high frequencies and occupy a large portion of a species range. These mutations exist as dominant cytotypes across populations and species. Geographical subdivision is lacking in both species, even though recurrent gene flow by both pollen and seed is severely limited. In total, the contrasting levels between historical and ongoing gene flow, large population sizes, a long lifespan, and slow mutation rates in both organelle DNAs have all likely contributed to the unusually long duration of paraphyly in cycads.}, } @article {pmid24403853, year = {2009}, author = {Westoff, CF and Higgins, JA}, title = {RELATIONSHIPS BETWEEN MEN'S GENDER ATTITUDES AND FERTILITY: Response to Puur, et al.'s "Men's childbearing desires and views of the male role in Europe at the dawn of the 21st century", Demographic Research 19: 1883-1912.}, journal = {Demographic research}, volume = {21}, number = {}, pages = {}, pmid = {24403853}, issn = {1435-9871}, support = {R24 HD047879/HD/NICHD NIH HHS/United States ; }, } @article {pmid19573187, year = {2009}, author = {Kennedy, TJ and Regehr, G and Baker, GR and Lingard, LA}, title = {'It's a cultural expectation...' The pressure on medical trainees to work independently in clinical practice.}, journal = {Medical education}, volume = {43}, number = {7}, pages = {645-653}, doi = {10.1111/j.1365-2923.2009.03382.x}, pmid = {19573187}, issn = {1365-2923}, mesh = {Clinical Competence/*standards ; Decision Making ; Education, Medical, Graduate/*standards ; Emergency Medicine/*education ; Humans ; Internal Medicine/*education ; Internship and Residency/standards ; Ontario ; Qualitative Research ; Safety Management/standards ; Students, Medical/*psychology ; }, abstract = {CONTEXT: Medical trainees demonstrate a reluctance to ask for help unless they believe it is absolutely necessary, a situation which could impact on the safety of patients. This study aimed to develop a theoretical exploration of the pressure on medical trainees to be independent and to generate theory-based approaches to the implications for patient safety of this pressure towards independent working.

METHODS: In Phase 1, 88 teaching team members from internal and emergency medicine were observed during clinical activities (216 hours), and 65 participants completed brief interviews. In Phase 2, 36 in-depth interviews were conducted using video vignettes. Data collection and analysis employed grounded theory methodology.

RESULTS: Participants conceived that the pressure towards independence in clinical work originated in trainees' desire to lay claim to the identity of a doctor (as a member of a group of autonomous high achievers), and in organisational issues such as heavy workloads and constant evaluations.

DISCUSSION: The identity and organisational issues related to the pressure towards independence were explored through the lenses of established theories from education and psychology. Consideration of Lave and Wenger's situated learning theory suggests that giving attention to the 'independent doctor' ideal, through measures such as involving trainees when their supervisors ask for help, could impact the safety of teaching team practice. Amalberti et al.'s migration model explains how pressures to maximise productivity and individual gain may cause teaching teams to migrate beyond the boundaries of safe practice and suggests that managing triggers (such as workload and high-stakes evaluations) for violations of safe practice might improve safety. Implementation and evaluation of these theory-based approaches to the safety of teaching team practice would contribute to a better understanding of the links between trainee independence and patient safety.}, } @article {pmid19558647, year = {2009}, author = {Minelli, A}, title = {Phylo-evo-devo: combining phylogenetics with evolutionary developmental biology.}, journal = {BMC biology}, volume = {7}, number = {}, pages = {36}, pmid = {19558647}, issn = {1741-7007}, mesh = {Animals ; *Biological Evolution ; Developmental Biology/*methods ; Diptera/classification ; Insecta/classification ; *Phylogeny ; }, abstract = {As a result of the integration of molecular and morphological approaches for the reconstruction of phylogenies, and of the intertwining of developmental and evolutionary biology, further prospects are open for a fruitful interaction between these two fields in what we may call a phylo-evo-devo approach.Wiegmann et al.'s molecular phylogeny of the holometabolous insect orders, recently published in BMC Biology, offers a good opportunity to revisit the inverted positions of wings and halteres in the Diptera and the Strepsiptera in terms of a putative homeotic mutation in the Hox gene Ultrabithorax. The main finding of this paper is that Strepsiptera are closely related to the Coleoptera rather than Diptera, as recently claimed. Through this exemplary case, the paper demonstrates the value of the reciprocal illumination we can expect from the integration of a good phylogeny and a sound knowledge of the evolvability of developmental mechanisms.}, } @article {pmid19554617, year = {2010}, author = {Griffin, NL and Richmond, BG}, title = {Joint orientation and function in great ape and human proximal pedal phalanges.}, journal = {American journal of physical anthropology}, volume = {141}, number = {1}, pages = {116-123}, doi = {10.1002/ajpa.21121}, pmid = {19554617}, issn = {1096-8644}, mesh = {Animals ; Female ; Gorilla gorilla/*anatomy & histology/physiology ; Humans ; Locomotion/physiology ; Male ; Pan troglodytes/*anatomy & histology/physiology ; Pongo pygmaeus/*anatomy & histology/physiology ; Sex Characteristics ; Toe Phalanges/*anatomy & histology/physiology ; }, abstract = {Previous studies have referred to the degree of dorsal canting of the base of the proximal phalanx as an indicator of human-like metatarsophalangeal joint function and thus a diagnostic trait of habitual bipedality in the fossil record. Here, we used a simple method to investigate differences in forefoot function on a finer scale. Building on Duncan et al.'s (Am J Phys Anthropol 93 [1994] 67-81) research, we tested whether dorsal canting reflects differences between sexes in locomotor behavior, whether habitual shoe wear influences dorsal canting in humans, and whether proximal joint morphology differs between rays in Pan and humans. Our results corroborate previous research in showing that humans have proximal phalanges with joint orientations that are significantly more dorsal than, but overlap with, those of great apes. We also found that male gorillas have significantly more dorsally canted second proximal phalanges than their female counterparts, while the opposite pattern between the sexes was found in Pan troglodytes. Inter-ray comparisons indicate that Pan have more dorsally canted first proximal phalanges than second proximal phalanges, while the opposite pattern was found in humans. Minimally shod humans have slightly but significantly more dorsally canted second proximal phalanges than those of habitually shod humans, indicating that phalanges of unshod humans provide the most appropriate comparative samples for analyses of early hominins. Overall, our analysis suggests that though the measurement of dorsal canting is limited in its sensitivity to certain intraspecific differences in function, phalangeal joint orientation reflects interspecific differences in joint function, with the caveat that different patterns of forefoot function during gait can involve similar articular sets of metatarsophalangeal joints.}, } @article {pmid19552810, year = {2009}, author = {Woolf, K and McManus, IC and Gill, D and Dacre, J}, title = {The effect of a brief social intervention on the examination results of UK medical students: a cluster randomised controlled trial.}, journal = {BMC medical education}, volume = {9}, number = {}, pages = {35}, pmid = {19552810}, issn = {1472-6920}, mesh = {Analysis of Variance ; Cluster Analysis ; Curriculum ; *Educational Measurement ; Educational Status ; *Ethnicity ; Humans ; Models, Educational ; Psychology ; *Self Concept ; Social Perception ; *Students, Medical ; United Kingdom ; }, abstract = {BACKGROUND: Ethnic minority (EM) medical students and doctors underperform academically, but little evidence exists on how to ameliorate the problem. Psychologists Cohen et al. recently demonstrated that a written self-affirmation intervention substantially improved EM adolescents' school grades several months later. Cohen et al.'s methods were replicated in the different setting of UK undergraduate medical education.

METHODS: All 348 Year 3 white (W) and EM students at one UK medical school were randomly allocated to an intervention condition (writing about one's own values) or a control condition (writing about another's values), via their tutor group. Students and assessors were blind to the existence of the study. Group comparisons on post-intervention written and OSCE (clinical) assessment scores adjusted for baseline written assessment scores were made using two-way analysis of covariance. All assessment scores were transformed to z-scores (mean = 0 standard deviation = 1) for ease of comparison. Comparisons between types of words used in essays were calculated using t-tests. The study was covered by University Ethics Committee guidelines.

RESULTS: Groups were statistically identical at baseline on demographic and psychological factors, and analysis was by intention to treat [intervention group EM n = 95, W n = 79; control group EM n = 77; W n = 84]. As predicted, there was a significant ethnicity by intervention interaction [F(4,334) = 5.74; p = 0.017] on the written assessment. Unexpectedly, this was due to decreased scores in the W intervention group [mean difference = 0.283; (95% CI = 0.093 to 0.474] not improved EM intervention group scores [mean difference = -0.060 (95% CI = -0.268 to 0.148)]. On the OSCE, both W and EM intervention groups outperformed controls [mean difference = 0.261; (95%CI = -0.047 to -0.476; p = 0.013)]. The intervention group used more optimistic words (p < 0.001) and more "I" and "self" pronouns in their essays (p < 0.001), whereas the control group used more "other" pronouns (p < 0.001) and more negations (p < 0.001).

DISCUSSION: Cohen et al.'s finding that a brief self-affirmation task narrowed the ethnic academic achievement gap was replicated on the written assessment but against expectations, this was due to reduced performance in the W group. On the OSCE, the intervention improved performance in both W and EM groups. In the intervention condition, participants tended to write about themselves and used more optimistic words than in the control group, indicating the task was completed as requested. The study shows that minimal interventions can have substantial educational outcomes several months later, which has implications for the multitude of seemingly trivial changes in teaching that are made on an everyday basis, whose consequences are never formally assessed.}, } @article {pmid19552763, year = {2009}, author = {Tahan, V and Atug, O and Akin, H and Eren, F and Tahan, G and Tarcin, O and Uzun, H and Ozdogan, O and Tarcin, O and Imeryuz, N and Ozguner, F and Celikel, C and Avsar, E and Tozun, N}, title = {Melatonin ameliorates methionine- and choline-deficient diet-induced nonalcoholic steatohepatitis in rats.}, journal = {Journal of pineal research}, volume = {46}, number = {4}, pages = {401-407}, doi = {10.1111/j.1600-079X.2009.00676.x}, pmid = {19552763}, issn = {1600-079X}, mesh = {Animals ; Apoptosis/drug effects ; Biomarkers ; Choline/metabolism ; Choline Deficiency/blood/drug therapy/*metabolism ; Cytokines/blood ; Diet ; Fatty Liver/blood/*drug therapy/*metabolism ; Glutathione/metabolism ; Histocytochemistry ; Liver/drug effects/enzymology ; Male ; Malondialdehyde/metabolism ; Melatonin/*pharmacology ; Methionine/*deficiency/metabolism ; Oxidative Stress/drug effects ; Rats ; Rats, Wistar ; Statistics, Nonparametric ; Superoxide Dismutase/metabolism ; }, abstract = {Nonalcoholic steatohepatitis (NASH) may progress to advanced fibrosis and cirrhosis. Mainly, oxidative stress and excessive hepatocyte apoptosis are implicated in the pathogenesis of progressive NASH. Melatonin is not only a powerful antioxidant but also an anti-inflammatory and anti-apoptotic agent. We aimed to evaluate the effects of melatonin on methionine- and choline-deficient diet (MCDD)-induced NASH in rats. Thirty-two male Wistar rats were divided into four groups. Two groups were fed with MCDD while the other two groups were fed a control diet, pair-fed. One of the MCDD groups and one of the control diet groups were administered melatonin 50 mg/kg/day intraperitoneally, and the controls were given a vehicle. After 1 month the liver tissue oxidative stress markers, proinflammatory cytokines and hepatocyte apoptosis were studied by commercially available kits. For grading and staging histological lesions, Brunt et al.'s system was used. Melatonin decreased oxidative stress, proinflammatory cytokines and hepatocyte apoptosis. The drug ameliorated the grade of NASH. The present study suggests that melatonin functions as a potent antioxidant, anti-inflammatory and antiapoptotic agent in NASH and may be a therapeutic option.}, } @article {pmid19543438, year = {2009}, author = {Dux, PE and Asplund, CL and Marois, R}, title = {Both exogenous and endogenous target salience manipulations support resource depletion accounts of the attentional blink: A reply to Olivers et al.}, journal = {Psychonomic bulletin & review}, volume = {16}, number = {1}, pages = {219-224}, pmid = {19543438}, issn = {1531-5320}, support = {R01 MH070776/MH/NIMH NIH HHS/United States ; }, abstract = {Input-control theories of the attentional blink (AB) suggest that this deficit results from impaired attentional selection caused by the post-Target 1 (T1) distractor (Di Lollo et al., 2005; Olivers et al., 2007). Accordingly, there should be no AB when there are no intervening distractors between the targets. Contrary to these hypotheses, Dux et al. (2008) observed an AB (T3 deficit) when three targets, from the same attentional set, were presented successively in a rapid stream of distractors if subjects increased the resources devoted to T1 processing, a result consistent with resource depletion accounts of the AB. However, Olivers et al. (this issue) argue that Dux et al.'s results can be better explained by the relationship between T1 and T2 rather than between T1 and T3, and by target discriminability effects. Here, we find that manipulating the resources subjects devote to T1, either exogenously (target perceptual salience) or endogenously (target task-relevance), affects T3 performance even when controlling for T2 and target discriminability differences. These results support Dux et al.'s conclusion that T1 resource depletion underlies the AB.}, } @article {pmid19538954, year = {2009}, author = {Zhang, S and Fan, J and Xu, X and Chen, G and Zhu, F and Yan, L}, title = {An experimental study of the use of ultrasound to facilitate the loading of trehalose into platelets.}, journal = {Cryobiology}, volume = {59}, number = {2}, pages = {135-140}, doi = {10.1016/j.cryobiol.2009.06.003}, pmid = {19538954}, issn = {1090-2392}, mesh = {Blood Platelets/*diagnostic imaging/*metabolism ; Humans ; Trehalose/*metabolism ; Ultrasonography ; }, abstract = {Trehalose is widely used as a freeze-drying protectant in biomaterial preservation. For this purpose, trehalose has to be loaded into the cells but this is difficult and many methods have been tried. The application of ultrasound can temporarily permeabilize cell membranes, which offers a non-chemical, non-viral, and non-invasive method of cellular drug delivery. Ultrasound is employed here to enhance the loading of trehalose into human platelets. Two frequencies were used, 25 kHz and 800 kHz. The estimated intensity of ultrasound in the sample was varied from 0 to 1.5 W/cm(2). The trehalose concentration in the platelets was 11.27+/-2.53 mmol/L when Wolkers et al.'s method was used without ultrasound. The application of 0.8 W/cm(2), 800 kHz ultrasound for 1h increased the concentration of trehalose loaded by 54%. The application of 0.8 W/cm(2), 25 kHz ultrasound for 30 min increased the trehalose concentration that was loaded by 172%. The number and mean volume of the platelets following ultrasonic radiation in these two cases remained normal as compared with fresh untreated platelets. Morphological examination of the radiated platelets showed slight changes. Although further work is needed, ultrasound has been shown to be efficient for the loading of trehalose into platelets.}, } @article {pmid19525067, year = {2009}, author = {Morimura, T and Hasaka, M}, title = {Bloch-wave-based STEM image simulation with layer-by-layer representation.}, journal = {Ultramicroscopy}, volume = {109}, number = {9}, pages = {1203-1209}, doi = {10.1016/j.ultramic.2009.05.007}, pmid = {19525067}, issn = {1879-2723}, abstract = {In a dynamical STEM image simulation by the Bloch-wave method, Allen et al. formulated a framework for calculating the cross-section for any incoherent scattering process from the inelastic scattering coefficients: thermal diffuse scattering (TDS) for high-angle annular dark-field (HAADF) and back-scattered electron (BSE) STEM, and ionization for electron energy-loss spectroscopy (EELS) and energy-dispersive X-ray spectroscopy (EDX) STEM. Furthermore, their method employed a skillfull approach for deriving the excitation amplitude and block diagonalization in the eigenvalue equation. In the present work, we extend their scheme to a layer-by-layer representation for application to inhomogeneous crystals that include precipitates, defects and atomic displacement. Calculations for a multi-layer sample of Si-Sb-Si were performed by multiplying Allen et al.'s block-diagonalized matrices. Electron intensities within the sample and EDX STEM images, as an example of the inelastic scattering, were calculated at various conditions. From the calculations, 3-dimensional STEM analysis was considered.}, } @article {pmid19518580, year = {2009}, author = {Victor, KK and Thomas, BB and Kofane, TC}, title = {Painlevé-integrability of a (2+1)-dimensional reaction-diffusion equation: exact solutions and their interactions.}, journal = {Physical review. E, Statistical, nonlinear, and soft matter physics}, volume = {79}, number = {5 Pt 2}, pages = {056605}, doi = {10.1103/PhysRevE.79.056605}, pmid = {19518580}, issn = {1539-3755}, abstract = {We investigate the singularity structure analysis of a (2+1)-dimensional coupled nonlinear extension of the reaction-diffusion (NLERD) equation by means of the Painlevé (P) test. Following the Weiss et al.'s formalism [J. Math. Phys. 24, 522 (1983)], we prove the arbitrariness of the expansion coefficients of the observables. Thus, without the use of the Kruskal's simplification, we obtain a Bäcklund transformation of the coupled NLERD equation via a consistent truncation procedure stemming from the Weiss 's methodology [J. Weiss, M. Tabor, and G. Carnevale, J. Math. Phys. 25, 13 (1984)]. In the wake of such results, we unveil a typical spectrum of localized and periodic coherent patterns. We also investigate the scattering properties of such structures and we unearth two peculiar soliton phenomena, namely, the fusion and the fission.}, } @article {pmid19504400, year = {2009}, author = {Cataño, L and Barlow, JA and Moyna, MI}, title = {A retrospective study of phonetic inventory complexity in acquisition of Spanish: implications for phonological universals.}, journal = {Clinical linguistics & phonetics}, volume = {23}, number = {6}, pages = {446-472}, pmid = {19504400}, issn = {0269-9206}, support = {R03 DC005754/DC/NIDCD NIH HHS/United States ; 05754//PHS HHS/United States ; }, mesh = {Aging ; *Child Language ; Child, Preschool ; Female ; Humans ; Infant ; Language ; *Learning ; Male ; *Phonetics ; Retrospective Studies ; Speech Production Measurement ; }, abstract = {This study evaluates 39 different phonetic inventories of 16 Spanish-speaking children (ages 0;11 to 5;1) in terms of hierarchical complexity. Phonetic featural differences are considered in order to evaluate the proposed implicational hierarchy of Dinnsen et al.'s phonetic inventory typology for English. The children's phonetic inventories are examined independently and in relation to one another. Five hierarchical complexity levels are proposed, similar to those of English and other languages, although with some language-specific differences. These findings have implications for theoretical assumptions about the universality of phonetic inventory development, and for remediation of Spanish-speaking children with phonological impairments.}, } @article {pmid19485457, year = {2009}, author = {Leung, K and Rempe, SB and von Lilienfeld, OA}, title = {Ab initio molecular dynamics calculations of ion hydration free energies.}, journal = {The Journal of chemical physics}, volume = {130}, number = {20}, pages = {204507}, pmid = {19485457}, issn = {1089-7690}, mesh = {Binding Sites ; Biomechanical Phenomena ; Catalysis ; *Computational Biology ; *Models, Chemical ; *Models, Statistical ; Physical Phenomena ; Potassium Chloride/chemistry ; *Substrate Specificity ; *Temperature ; *Thermodynamics ; Water/*chemistry ; }, abstract = {We apply ab initio molecular dynamics (AIMD) methods in conjunction with the thermodynamic integration or "lambda-path" technique to compute the intrinsic hydration free energies of Li(+), Cl(-), and Ag(+) ions. Using the Perdew-Burke-Ernzerhof functional, adapting methods developed for classical force field applications, and with consistent assumptions about surface potential (phi) contributions, we obtain absolute AIMD hydration free energies (DeltaG(hyd)) within a few kcal/mol, or better than 4%, of Tissandier et al.'s [J. Phys. Chem. A 102, 7787 (1998)] experimental values augmented with the SPC/E water model phi predictions. The sums of Li(+)/Cl(-) and Ag(+)/Cl(-) AIMD DeltaG(hyd), which are not affected by surface potentials, are within 2.6% and 1.2 % of experimental values, respectively. We also report the free energy changes associated with the transition metal ion redox reaction Ag(+)+Ni(+)-->Ag+Ni(2+) in water. The predictions for this reaction suggest that existing estimates of DeltaG(hyd) for unstable radiolysis intermediates such as Ni(+) may need to be extensively revised.}, } @article {pmid19468775, year = {2009}, author = {Debarge, R and Chotel, F and Gazarian, A and Viola, J and Berard, J}, title = {Failed vascularized proximal fibular epiphyseal transfer for hip reconstruction following infection in children.}, journal = {Journal of children's orthopaedics}, volume = {3}, number = {4}, pages = {325-330}, pmid = {19468775}, issn = {1863-2521}, abstract = {PURPOSE: Treatment of the sequellae of hip infection with epiphyseal destruction in children has had limited success to date. The aim of this study was to report mid-term results after hip epiphyseal reconstruction using a proximal vascularized fibular graft in three children presenting with massive epiphyseal destruction of the proximal femur following infection.

METHODS: Three children suffered from hip articular destruction type IVB according to the Choi classification after neonatal septic arthritis. The mean age at reconstruction was 4.3 years (range 3-6 years). The Hunka et al. criteria were used to evaluate the functional results, and the clinical evaluation was based on the Musculo-Skeletal Tumor Society (MSTS) score. Growth and fusion of the graft and hip morphology were evaluated on simple X-rays and by magnetic resonance imaging (MRI). A ratio between cephalic diameter and inter-acetabular gap was defined on the MRI scan as the "acetabular filling index".

RESULTS: No intraoperative complication was reported. With a mean follow-up of 4.8 years (3-6 years), the MSTS score was 22.7/30 (range 20-26), while the average lower limb length discrepancy was 3 cm. Patient 1 required a secondary derotation osteotomy of the femur because of abnormal external rotation and a bad result due to the unexplained occurrence of a painful and stiff hip joint. A secondary distal transfer of the greater trochanter was performed in patient 2, and good results based on Hunka et al.'s criteria were achieved. The X-rays of patients 1 and 2 showed signs of bone growth and a major remodeling process; the MRI filling indices were 83 and 67%, respectively. Patient 3 developed an early slipped capital (fibular) epiphysis 1 month postoperatively, which was treated by percutaneous pinning; this early complication led to a bad result with full resorption of the graft.

CONCLUSIONS: In contrast to its success in upper limb reconstruction, in this series of three patients with hip articular destruction, articular reconstruction using a vascularized proximal fibula graft was disappointing and led to unsatisfactory results in terms of hip reconstruction. Such a procedure is complex and highly demanding, necessitating extremely intensive post-operative care. An early slipped capital epiphysis can lead to full graft resorption. Consequently, despite important adaptation and remodeling of the graft, the authors do not recommend this procedure at this location.}, } @article {pmid19453576, year = {2010}, author = {Kim, SY and Kim, GY and Jo, SA and Lee, EH and Cho, EH and Hwang, SH and Lee, EY}, title = {A novel hemoglobin variant beta135(H13) Ala > Asp identified in an asymptomatic Korean family by direct sequencing: suggesting a new insight into Hb Beckman mutation.}, journal = {International journal of laboratory hematology}, volume = {32}, number = {1 Pt 1}, pages = {e175-8}, doi = {10.1111/j.1751-553X.2009.01156.x}, pmid = {19453576}, issn = {1751-553X}, mesh = {Adult ; Amino Acid Substitution ; Asian People/genetics ; Base Sequence ; Female ; Glycated Hemoglobin/analysis ; Hemoglobins, Abnormal/*genetics ; Humans ; Male ; Middle Aged ; }, abstract = {This article describes the clinical observation of a novel hemoglobin (Hb) variant found during the course of routine blood testing on a 61-year-old subject. The Hb variant was observed during HbA1c testing by ion-exchange high-performance liquid chromatography. Alkaline electrophoresis and DNA sequencing confirmed the presence of a new Hb variant, HBB:c.407C > A (p.Ala136Asp). This mutation has been reported to induce Hb Beckman variant in the Globin Gene Server. However, it was different from the only experimental report for Hb Beckman by Rahbar, Lee & Asmeron (p.Ala136Glu; Hb Beckman alpha2 beta2 135(H13) ala-to-glu: a new unstable variant and reduced oxygen affinity. Blood 78, 204a). And our case was asymptomatic with normal lab findings, while Rahbar et al.'s case showed the clinical manifestations of chronic anemia. This would be a report for a novel Hb variant suggesting new insight of Hb Beckman variant. This would be a report of a novel Hb variant suggesting new insights into Hb Beckman variant.}, } @article {pmid19449181, year = {2009}, author = {Miura, N and Imai, H and Kikuchi, S and Hayashi, S and Endoh, M and Kawamura, T and Tomino, Y and Moriwaki, K and Kiyomoto, H and Kohagura, K and Nakazawa, E and Kusano, E and Mochizuki, T and Nomura, S and Sasaki, T and Kashihara, N and Soma, J and Tomo, T and Nakabayashi, I and Yoshida, M and Watanabe, T}, title = {Tonsillectomy and steroid pulse (TSP) therapy for patients with IgA nephropathy: a nationwide survey of TSP therapy in Japan and an analysis of the predictive factors for resistance to TSP therapy.}, journal = {Clinical and experimental nephrology}, volume = {13}, number = {5}, pages = {460-466}, pmid = {19449181}, issn = {1437-7799}, mesh = {Adolescent ; Adult ; Combined Modality Therapy ; Data Collection ; Female ; Glomerulonephritis, IGA/*drug therapy/pathology/*surgery ; Humans ; Japan ; Male ; Middle Aged ; Multivariate Analysis ; ROC Curve ; Remission Induction ; *Steroids/administration & dosage/therapeutic use ; Surveys and Questionnaires ; *Tonsillectomy ; Treatment Outcome ; Young Adult ; }, abstract = {BACKGROUND: Tonsillectomy and steroid pulse (TSP) therapy was proposed as a curative treatment for IgA nephropathy by Hotta et al. (Am J Kidney Dis 38:736-742, 2001) based on data that about 50% of patients achieved clinical remission (CR) of urinary abnormalities.

MATERIALS AND METHODS: As a primary survey, we sent a questionnaire and letter to 848 hospitals in Japan, each of which employed a Fellow of the Japanese Society of Nephrology between October and December of 2006, in order to gather information about the prevalence and efficacy of TSP therapy for patients with IgA nephropathy. As a secondary survey, we collected data from both low- and high-CR-rate groups to determine which factors predicted resistance to TSP therapy.

RESULTS: A total of 2,746 patients received TSP therapy between 2000 and 2006. The CR rates, calculated by measuring urinary criteria 6 and 12 months after TSP therapy, were 32.0% (347/1,085) and 45.6% (452/991), respectively. Analysis of the 30 hospitals in which TSP therapy had been performed on at least ten patients revealed that the CR rates varied from below 10% to 100%. A secondary survey of ten hospitals revealed that, after correction of the CR rate from each hospital, patients could be categorized into three groups: those with a low CR rate (122 patients in four hospitals), a middle CR rate (78 patients in four hospitals), and a high CR rate (103 patients in two hospitals). The CR rate of all patients (N = 303) was 54.1%. A comparison of patient data between the low- and high-CR-rate groups showed a significant difference in age at onset (years; P = 0.05), amount of proteinuria (g/day; P = 0.02), total protein (g/dl; P = 0.02), pathological grade (P = 0.009), and prognostic score as described by Wakai et al. [Nephrol Dial Transplant 21:2800-2808, 2006, (P = 0.04)]. Univariate analysis revealed that there was a significant difference between non-CR and CR subgroups in duration from diagnosis until TSP therapy (6.9 +/- 6.8 versus 5.3 +/- 5.2 years; P = 0.02), amount of proteinuria (1.5 +/- 1.6 versus 0.8 +/- 0.8 g/day; P < 0.0001), serum creatinine (0.99 +/- 0.40 versus 0.87 +/- 0.34 mg/dl; P = 0.006), pathological grade (P = 0.0006), and Wakai et al.'s prognostic score (37.4 +/- 17.8 versus 28.1 +/- 15.1; P < 0.0001). A multivariate logistic analysis demonstrated that resistance to TSP therapy depends on age at onset, amount of proteinuria, hematuria grade, and pathological grade, and a score predicting resistance to TSP therapy could be derived by the formula: [(-0.0330) x (age) + (0.4772) x log (amount of proteinuria) - (0.0273) x (hematuria grade: 0, 1, 2, and 3) + (0.7604) x (pathological grade: 1, 2, 3, and 4) - 0.1894]. A receiver operating characteristic (ROC) curve showed that patients with a resistance score of greater than -0.02 easily resist TSP therapy (sensitivity 69%, specificity 75%, positive likelihood ratio 2.76).

CONCLUSION: TSP therapy shows promise as a treatment that can bring about CR of urinary abnormalities, but unfortunately the average CR rate is about 50% at 1 year after treatment. Predictive factors for resistance to TSP therapy are age at onset, amount of proteinuria, hematuria grade, and pathological grade. The present study suggests that patients with either early-stage or mild to moderate IgA nephropathy easily achieve CR following TSP therapy, whereas patients with late-stage or severe disease are prone to TSP therapy resistance.}, } @article {pmid19438924, year = {2010}, author = {Kang, JK and Ryu, JW and Choi, JH and Merrill, RL and Kim, ST}, title = {Application of ICHD-II criteria for headaches in a TMJ and orofacial pain clinic.}, journal = {Cephalalgia : an international journal of headache}, volume = {30}, number = {1}, pages = {37-41}, doi = {10.1111/j.1468-2982.2009.01866.x}, pmid = {19438924}, issn = {1468-2982}, mesh = {Adolescent ; Adult ; Age Distribution ; Cluster Headache/classification/diagnosis/epidemiology ; Facial Pain/diagnosis/*epidemiology/physiopathology ; Female ; *Headache/classification/diagnosis/epidemiology ; Humans ; Male ; Masseter Muscle/physiopathology ; Migraine with Aura/classification/diagnosis/epidemiology ; Migraine without Aura/classification/diagnosis/epidemiology ; Pain Clinics ; Prevalence ; Sex Distribution ; Temporal Muscle/physiopathology ; Temporomandibular Joint Disorders/diagnosis/*epidemiology/physiopathology ; Tension-Type Headache/classification/diagnosis/epidemiology ; Young Adult ; }, abstract = {The aim of this study was to identify and diagnose headache in a temporomandibular joint and orofacial pain clinic population using the second edition of The International Classification of Headache Disorder criteria. In 502 temporomandibular disorder and orofacial pain patients, 246 patients (49%) were diagnosed with tension-type headache (TTH), followed by migraine without aura (14.5%), probable migraine (12.9%), migraine with aura (7%), probable TTH (4.8%) and cluster headache (0.2%). The prevalence of headaches was compared between male and female patients, and the prevalence of migraine was found to be higher in women than in men. In evaluating by age, the prevalence of migraine was highest in patients in their 20s and 30s and declined as age increased above 40. TTH showed the highest rate throughout all age groups, but it also decreased as age increased. In this study, the prevalence of migraine was lower than that reported in Dr Kim et al.'s study, and the prevalence of TTH much higher than that reported in the previous study. Of the headache patients, 81.1% presented with masseter muscle pain and 47.8% with temporal muscle pain. This finding suggests that pericranial muscle pain may be an inducing factor of primary headache.}, } @article {pmid19429953, year = {2009}, author = {Chua, FK}, title = {A new object captures attention--but only when you know it's new.}, journal = {Attention, perception & psychophysics}, volume = {71}, number = {4}, pages = {699-711}, doi = {10.3758/APP.71.4.699}, pmid = {19429953}, issn = {1943-3921}, mesh = {*Attention ; Awareness ; *Discrimination Learning ; Humans ; Imagination ; *Memory, Short-Term ; *Orientation ; *Pattern Recognition, Visual ; Perceptual Masking ; Psychophysics ; Reaction Time ; Size Perception ; }, abstract = {Two hypotheses have been advanced to explain why an object appearing suddenly in an empty location captures attention. According to the first hypothesis, the visual transients that accompany an abrupt onset automatically trigger attentional orienting toward the object. The second hypothesis claims that the visual system regards the onset as an advent of a new object, and the latter's novelty causes attention to be drawn toward it. To discriminate between these two accounts, Franconeri, Hollingworth, and Simons (2005) introduced a procedure in which an object was added to the display but, crucially, the object's onset transients were concealed. Their results showed that this additional object failed to capture attention, which they interpreted as evidence against the new-object hypothesis. But the Franconeri et al. procedure could somehow have impeded the visual system from identifying the additional object as new. In three experiments, Franconeri et al.'s results were first replicated and extended. Further, it was shown that when the conditions facilitated the encoding of the locations of the old items, the new object did succeed in capturing attention.}, } @article {pmid19403538, year = {2009}, author = {Wicherts, JM and Johnson, W}, title = {Group differences in the heritability of items and test scores.}, journal = {Proceedings. Biological sciences}, volume = {276}, number = {1667}, pages = {2675-2683}, pmid = {19403538}, issn = {0962-8452}, mesh = {Humans ; Intelligence/*genetics ; Intelligence Tests/*statistics & numerical data ; }, abstract = {It is important to understand potential sources of group differences in the heritability of intelligence test scores. On the basis of a basic item response model we argue that heritabilities which are based on dichotomous item scores normally do not generalize from one sample to the next. If groups differ in mean ability, the functioning of items at different ability levels may result in group differences in the heritability of items, even when these items function equivalently across groups and the heritability of the underlying ability is equal across groups. We illustrate this graphically, by computer simulation, and by focusing on several problems associated with a recent study by Rushton et al. who argued that the heritability estimates of items of Raven's Progressive Matrices test in North-American twin samples generalized to other population groups, and hence that the population group differences on this test of general mental ability (or intelligence) had a substantial genetic component. Our results show that item heritabilities are strongly dependent on the group on which the heritabilities were based. Rushton et al.'s results were artefactual and do not speak to the nature of population group differences in intelligence test performance.}, } @article {pmid19382878, year = {2009}, author = {Dubois, JM}, title = {The biomedical ethics ontology proposal: excellent aims, questionable methods.}, journal = {Journal of empirical research on human research ethics : JERHRE}, volume = {4}, number = {1}, pages = {59-62}, pmid = {19382878}, issn = {1556-2646}, support = {UL1 RR024992/RR/NCRR NIH HHS/United States ; }, mesh = {Automation ; *Decision Support Techniques ; Ethical Analysis/*methods ; Humans ; Peer Review, Research/legislation & jurisprudence/*methods ; Reproducibility of Results ; *Social Control, Formal ; United States ; }, abstract = {KOEPSELL ET AL. (2009) DESCRIBE AN IDEAL biomedical ethics committee environment with efficiencies such as electronic and universal application forms and consent templates, automated decision-trees, and broad sharing of data. However, it is unclear that a biomedical ethics ontology (BMEO) is necessary or even helpful in establishing such environment. Two features of any applied ontology are particularly problematic in establishing a useful BMEO: (1) an ontology is a description of a domain of reality; and (2) the description is subject to ongoing revision as it is developed through open processes, e.g., the use of a wiki. A BMEO would need to address two main kinds of entities, regulatory definitions and ethical concepts, and is ill-suited to both. Regulatory definitions are fiats and ought to be adopted verbatim to ensure compliance, but in such cases we do not need the assistance of ontologists, and their modes of working (constant revision within open wiki-based communities) might even be counterproductive. Ethical concepts within pluralistic societies are social constructs, not a priori concepts or biological natural kinds, and the prospects of generating intuitive definitions that enjoy broad acceptance across cultures and institutional settings are slim. In making these arguments, I draw from the writings of leading applied ontologists and Koepsell et al.'s own proof of concept.}, } @article {pmid19380896, year = {2009}, author = {Lionello-DeNolf, KM}, title = {The search for symmetry: 25 years in review.}, journal = {Learning & behavior}, volume = {37}, number = {2}, pages = {188-203}, pmid = {19380896}, issn = {1543-4494}, support = {P30 HD004147/HD/NICHD NIH HHS/United States ; R01 HD039816/HD/NICHD NIH HHS/United States ; HD04147/HD/NICHD NIH HHS/United States ; HD39816/HD/NICHD NIH HHS/United States ; }, mesh = {Animals ; *Association Learning ; *Behavior, Animal ; *Conditioning, Psychological ; *Discrimination Learning ; *Generalization, Stimulus ; Humans ; }, abstract = {It has been 25 years since the publication of Sidman et al.'s (1982) report on the search for symmetry in nonhuman animals. They attributed their nonhuman subjects' failure to the absence of some critical experiences (e.g., exemplar training, control of location variables, and generalized identity matching). Since then, species ranging from rats to chimpanzees have been tested on symmetry, and the results have been equivocal. Twenty-four investigations of symmetry in nonhumans are reviewed to determine whether the underlying factors first addressed by Sidman et al. (1982) have been verified and whether new factors have been identified. The emergent picture shows that the standard procedures as typically implemented on a three-key apparatus are insufficient by themselves to produce emergent symmetry in nonhumans. Recent successful demonstrations of symmetry in sea lions and pigeons have clarified certain important stimulus control variables (i.e., select and reject control) and suggest avenues for future research. Reliable symmetry may be achievable with nonhumans if training and test procedures that encourage compatible stimulus-control topographies and relations are designed.}, } @article {pmid19379050, year = {2009}, author = {Staub, A and Grant, M and Clifton, C and Rayner, K}, title = {Phonological typicality does not influence fixation durations in normal reading.}, journal = {Journal of experimental psychology. Learning, memory, and cognition}, volume = {35}, number = {3}, pages = {806-814}, pmid = {19379050}, issn = {0278-7393}, support = {HD26765/HD/NICHD NIH HHS/United States ; R37 HD026765/HD/NICHD NIH HHS/United States ; HD18708/HD/NICHD NIH HHS/United States ; R01 HD026765/HD/NICHD NIH HHS/United States ; R01 HD018708/HD/NICHD NIH HHS/United States ; }, mesh = {Attention ; Comprehension ; *Eye Movements ; *Fixation, Ocular ; Humans ; *Phonetics ; Psycholinguistics ; *Reaction Time ; *Reading ; *Semantics ; }, abstract = {Using a word-by-word self-paced reading paradigm, T. A. Farmer, M. H. Christiansen, and P. Monaghan (2006) reported faster reading times for words that are phonologically typical for their syntactic category (i.e., noun or verb) than for words that are phonologically atypical. This result has been taken to suggest that language users are sensitive to subtle relationships between sound and syntactic function and that they make rapid use of this information in comprehension. The present article reports attempts to replicate this result using both eyetracking during normal reading (Experiment 1) and word-by-word self-paced reading (Experiment 2). No hint of a phonological typicality effect emerged on any reading-time measure in Experiment 1, nor did Experiment 2 replicate Farmer et al.'s finding from self-paced reading. Indeed, the differences between condition means were not consistently in the predicted direction, as phonologically atypical verbs were read more quickly than phonologically typical verbs, on most measures. Implications for research on visual word recognition are discussed.}, } @article {pmid19379019, year = {2009}, author = {Gawronski, B and LeBel, EP and Peters, KR and Banse, R}, title = {Methodological issues in the validation of implicit measures: comment on De Houwer, Teige-Mocigemba, Spruyt, and Moors (2009).}, journal = {Psychological bulletin}, volume = {135}, number = {3}, pages = {369-372}, doi = {10.1037/a0014820}, pmid = {19379019}, issn = {0033-2909}, mesh = {*Association ; *Attitude ; *Automatism ; Cues ; Humans ; Internal-External Control ; Memory/physiology ; Personality Tests/*standards ; Psychology/*methods ; Reproducibility of Results ; Task Performance and Analysis ; }, abstract = {J. De Houwer, S. Teige-Mocigemba, A. Spruyt, and A. Moors's normative analysis of implicit measures provides an excellent clarification of several conceptual ambiguities surrounding the validation and use of implicit measures. The current comment discusses an important, yet unacknowledged, implication of J. De Houwer et al.'s analysis, namely, that investigations addressing the proposed implicitness criterion (i.e., does the relevant psychological attribute influence measurement outcomes in an automatic fashion?) will be susceptible to fundamental misinterpretations if they are conducted independently of the proposed what criterion (i.e., is the measurement outcome causally produced by the psychological attribute the measurement procedure was designed to assess?). As a solution, it is proposed that experimental validation studies should be combined with a correlational approach in order to determine whether a given manipulation influenced measurement scores via variations in the relevant psychological attribute or via secondary sources of systematic variance. (PsycINFO Database Record (c) 2009 APA, all rights reserved).}, } @article {pmid19378385, year = {2009}, author = {Siekmeier, PJ}, title = {Evidence of multistability in a realistic computer simulation of hippocampus subfield CA1.}, journal = {Behavioural brain research}, volume = {200}, number = {1}, pages = {220-231}, pmid = {19378385}, issn = {1872-7549}, support = {K08 MH072771/MH/NIMH NIH HHS/United States ; P50 MH060450/MH/NIMH NIH HHS/United States ; 5K08MH072771/MH/NIMH NIH HHS/United States ; 5P50MH060450/MH/NIMH NIH HHS/United States ; }, mesh = {Action Potentials/physiology ; Animals ; Axons/metabolism/physiology ; Calcium-Binding Proteins/metabolism ; *Computer Simulation ; Hippocampus/*cytology ; *Models, Neurological ; Nerve Net/physiology ; Neural Networks, Computer ; Neural Pathways ; Neurons/classification/cytology/*physiology ; Synapses/physiology ; }, abstract = {The manner in which hippocampus processes neural signals is thought to be central to the memory encoding process. A theoretically oriented literature has suggested that this is carried out via "attractors" or distinctive spatio-temporal patterns of activity. However, these ideas have not been thoroughly investigated using computational models featuring both realistic single-cell physiology and detailed cell-to-cell connectivity. Here we present a 452 cell simulation based on Traub et al.'s pyramidal cell [Traub RD, Jefferys JG, Miles R, Whittington MA, Toth K. A branching dendritic model of a rodent CA3 pyramidal neurone. J Physiol (Lond) 1994;481:79-95] and interneuron [Traub RD, Miles R, Pyramidal cell-to-inhibitory cell spike transduction explicable by active dendritic conductances in inhibitory cell. J Comput Neurosci 1995;2:291-8] models, incorporating patterns of synaptic connectivity based on an extensive review of the neuroanatomic literature. When stimulated with a one second physiologically realistic input, our simulated tissue shows the ability to hold activity on-line for several seconds; furthermore, its spiking activity, as measured by frequency and interspike interval (ISI) distributions, resembles that of in vivo hippocampus. An interesting emergent property of the system is its tendency to transition from stable state to stable state, a behavior consistent with recent experimental findings [Sasaki T, Matsuki N, Ikegaya Y. Metastability of active CA3 networks. J Neurosci 2007;27:517-28]. Inspection of spike trains and simulated blockade of K(AHP) channels suggest that this is mediated by spike frequency adaptation. This finding, in conjunction with studies showing that apamin, a K(AHP) channel blocker, enhances the memory consolidation process in laboratory animals, suggests the formation of stable attractor states is central to the process by which memories are encoded. Ways that this methodology could shed light on the etiology of mental illness, such as schizophrenia, are discussed.}, } @article {pmid19375046, year = {2009}, author = {Burgin, M and Gairard-Dory, A- and Mennecier, B and Molard, A and Beretz, L and Quoix, A-}, title = {[First-line treatment with pemetrexed in association with cisplatin in patients with non-operable malignant pleural mesothelioma].}, journal = {Revue de pneumologie clinique}, volume = {65}, number = {2}, pages = {75-83}, doi = {10.1016/j.pneumo.2008.12.002}, pmid = {19375046}, issn = {0761-8417}, mesh = {Aged ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Cisplatin/*administration & dosage ; Female ; Glutamates/*administration & dosage ; Guanine/administration & dosage/*analogs & derivatives ; Humans ; Male ; Mesothelioma/*drug therapy/mortality ; Middle Aged ; Pemetrexed ; Pleural Neoplasms/*drug therapy/mortality ; Retrospective Studies ; }, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive disease with a poor prognosis. The optimal treatment of MPM was not clearly defined, until the publication of the multicentre, controlled and randomized phase III trial by Vogelzang et al. in 2003, which made the pemetrexed-cisplatin association the gold standard for the non-operable stages. Eleven patients with histologically proven pleural mesothelioma, not candidates for curative surgery, were assessed for eligibility and treated in our hospital. The response rate was similar to the reference study and the toxicity was acceptable. The median survival time was 12.7 months with an objective response rate of 45.5%. The median time to progression was 7.7 months. Neutropenia (all grades included) was the most common haematological toxicity (42.1%) although only one grade 3/4 was noted. Grade 3/4 anaemia and thrombocytopenia were not reported. Nausea and vomiting were the most commonly reported clinical toxicities with 81.8% reported (all grades included). One cutaneous allergic reaction was reported. The combination of pemetrexed and cisplatin chemotherapy provided the best objectives responses, but new therapeutic regimens are still warranted for these patients with a poor prognosis. The results were similar to those obtained in the Vogelzang et al.'s trial despite a selection bias because they correspond to 36.7% of the total recruitment in the unit.}, } @article {pmid19370097, year = {2009}, author = {Wang, H and Kemao, Q and Gao, W and Lin, F and Seah, HS}, title = {Fringe pattern denoising using coherence-enhancing diffusion.}, journal = {Optics letters}, volume = {34}, number = {8}, pages = {1141-1143}, doi = {10.1364/ol.34.001141}, pmid = {19370097}, issn = {0146-9592}, abstract = {Electronic speckle pattern interferometry is one of the methods measuring the displacement on object surfaces in which fringe patterns need to be evaluated. Noise is one of the key problems affecting further processing and reducing measurement quality. We propose an application of coherence-enhancing diffusion to fringe-pattern denoising. It smoothes a fringe pattern along directions both parallel and perpendicular to fringe orientation with suitable diffusion speeds to more effectively reduce noise and improve fringe-pattern quality. It is a generalized work of Tang's et al.'s [Opt. Lett.33, 2179 (2008)] model that only smoothes a fringe pattern along fringe orientation. Since our model diffuses a fringe pattern with an additional direction, it is able to denoise low-density fringes as well as improve denoising effectiveness for high-density fringes. Theoretical analysis as well as simulation and experimental verifications are addressed.}, } @article {pmid19369742, year = {2009}, author = {Hill, LK and Siebenbrock, A}, title = {Are all measures created equal? Heart rate variability and respiration - biomed 2009.}, journal = {Biomedical sciences instrumentation}, volume = {45}, number = {}, pages = {71-76}, pmid = {19369742}, issn = {0067-8856}, abstract = {There is considerable controversy with regards to which index of heart rate variability (HRV) is the most reliable across multiple situations. Recent evidence from Pentilla and colleagues (2001) suggests that certain indices of HRV appear to be less affected by fluctuations in respiration, and may thus be a more robust indicator of parasympathetic (vagal) influence. In the present investigation, we sought to replicate and extend this report by exploring the relations between, impedance cardiography-derived respiration parameters (rate and amplitude) and time and frequency domain indices of heart rate variability in a multiethnic sample of healthy men and women (n=39; mean age = 20.33 +/- 3.47yrs). Preliminary results support Pentilla et al.'s finding that rMSSD is relatively free of respiratory influences (r = -.06 to .21; ns), and extends this work to a multiethnic sample. In conclusion, some measures of HRV appear to be relatively free of respiratory influences while others appear less so, independent of the subjects' ethnicity.}, } @article {pmid19365761, year = {2009}, author = {Tellegen, A and Ben-Porath, YS and Sellbom, M}, title = {Construct validity of the MMPI-2 restructured clinical (RC) scales: reply to Rouse, Greene, Butcher, Nichols, and Williams.}, journal = {Journal of personality assessment}, volume = {91}, number = {3}, pages = {211-21; discussion 222-6}, doi = {10.1080/00223890902794192}, pmid = {19365761}, issn = {1532-7752}, mesh = {Humans ; *MMPI ; Mental Disorders/*diagnosis/psychology ; Proxy ; Surveys and Questionnaires ; }, abstract = {Rouse, Greene, Butcher, Nichols, and Williams (2008) repeat two claims about the MMPI-2 Restructured (RC) scales. One asserts that the correlations of RC scales with parent Clinical scales are modest compared to the correlations with other existing MMPI-2 scales. In response, we reiterate that the RC scales were not meant to emulate the divergent and overlapping content of the Clinical scales. Instead, each represents a distinctive Clinical scale component. Although individually focused, the RC scales span collectively a wide range of content and used as multivariate predictors, account for most of the variance of each Clinical scale. Rouse et al. also claim that most RC scales are redundant with existing MMPI-2 scales, which they propose as substitutes ("proxies"). However, our analyses of Rouse et al.'s database and of our own data show that several of their proposed proxies are far less mutually distinguishable than are the RC scale counterparts. Furthermore, several Clinical scales are more successfully, and none are less successfully, accounted for by RC scales than by proxies. In response to Rouse et al.'s neglect of a body of empirical findings supporting the construct validity of the RC scales, we also review the relevant research literature.}, } @article {pmid19364232, year = {2009}, author = {Brown, GS and White, KG}, title = {Reinforcer probability, reinforcer magnitude, and the reinforcement context for remembering.}, journal = {Journal of experimental psychology. Animal behavior processes}, volume = {35}, number = {2}, pages = {238-249}, doi = {10.1037/a0013864}, pmid = {19364232}, issn = {0097-7403}, mesh = {Animals ; Behavior, Animal/*physiology ; Columbidae ; Conditioning, Operant/physiology ; Memory/*physiology ; *Models, Psychological ; Probability ; *Reinforcement, Psychology ; Time Factors ; }, abstract = {Traditional theories of delayed matching-to-sample performance do not predict that accuracy will improve when absolute levels of reinforcement are increased. This prediction emerges only when reinforcement context is considered (J. A. Nevin, M. Davison, A. L. Odum, & T. A. Shahan, 2007). To provide quantitative data, the authors factorially manipulated between conditions the probability and duration of reinforcement for correct choices by pigeons. In Experiment 1, increasing the value of either variable improved initial discriminability of the forgetting functions, but did not affect the rate of forgetting. In Experiment 2, initial discriminability covaried with changes in choice immediacy and trial completion rate, suggesting a relationship with response strength consistent with Nevin et al.'s behavioral momentum model. Adding reinforcement context to K. G. White and J. T. Wixted's (1999) model also generates predictions consistent with the present experiments and with the effects of manipulating extraneous reinforcement. The inclusion of reinforcement context thus improves predictions of delayed matching-to-sample performance.}, } @article {pmid19348116, year = {2009}, author = {Martin, S}, title = {Comment: there may be compositional effects, but they do not work that way.}, journal = {Demography}, volume = {46}, number = {1}, pages = {203-8; discussion 211-9}, pmid = {19348116}, issn = {0070-3370}, mesh = {Adult ; Black or African American/statistics & numerical data ; Birth Rate/ethnology/trends ; Censuses ; Female ; *Fertility ; Humans ; Illegitimacy/*statistics & numerical data ; Marriage/*ethnology/*statistics & numerical data/trends ; Models, Statistical ; Population Dynamics ; Pregnancy ; United States ; White People/statistics & numerical data ; Young Adult ; }, abstract = {This analysis joins the debate on how declines in marriage have shifted the composition of the unmarried and married populations in the United States, and how compositional shifts have affected nonmarital birth rates. Gray, Stockard, and Stone (2006) presented one model for compositional effects that Ermisch (2009) challenged with alternative statistical tests. I propose an alternative model for compositional shifts based not on theory but on observed marriage and fertility patterns. The results from this alternative model are consistent with Ermisch's findings yet support Gray et al.'s general case that compositional effects have had an important influence on nonmarital birth rates.}, } @article {pmid19335584, year = {2009}, author = {Stephenson, A and Todres, M and Jones, R}, title = {Reply to Dornan et al.'s 'On evidence'.}, journal = {Medical education}, volume = {43}, number = {4}, pages = {390-391}, doi = {10.1111/j.1365-2923.2009.03306.x}, pmid = {19335584}, issn = {1365-2923}, mesh = {Education, Medical/*methods ; Evidence-Based Medicine/*methods ; Research/*standards ; }, } @article {pmid19331511, year = {2009}, author = {van der Wel, RP and Eder, JR and Mitchel, AD and Walsh, MM and Rosenbaum, DA}, title = {Trajectories emerging from discrete versus continuous processing models in phonological competitor tasks: a commentary on Spivey, Grosjean, and Knoblich (2005).}, journal = {Journal of experimental psychology. Human perception and performance}, volume = {35}, number = {2}, pages = {588-594}, doi = {10.1037/0096-1523.35.2.588}, pmid = {19331511}, issn = {0096-1523}, mesh = {Choice Behavior ; Humans ; Language ; *Models, Neurological ; *Models, Psychological ; Movement ; Psycholinguistics ; *Psychomotor Performance ; *Speech Perception ; *Tool Use Behavior ; User-Computer Interface ; }, abstract = {M. J. Spivey, M. Grosjean, and G. Knoblich showed that in a phonological competitor task, participants' mouse cursor movements showed more curvature toward the competitor item when the competitor and target were phonologically similar than when the competitor and target were phonologically dissimilar. Spivey et al. interpreted this result as evidence for continuous cascading of information during the processing of spoken words. Here we show that the results of Spivey et al.need not be ascribed to continuous speech processing. Instead, their results can be ascribed to discrete processing of speech, provided one appeals to an already supported model of motor control that asserts that switching movements from 1 target to another relies on superposition of the 2nd movement onto the 1st. The latter process is a continuous cascade, a fact that indirectly strengthens the plausibility of continuous cascade models. However, the fact that we can simulate the results of Spivey et al.with a continuous motor output model and a discrete perceptual model shows that the implications of Spivey et al.'s experiment are less clear than these authors supposed.}, } @article {pmid19322532, year = {2009}, author = {Bauer, N and Heckmann, K and Sand, A and Lisson, JA}, title = {Craniofacial growth patterns in patients with congenitally missing permanent teeth.}, journal = {Journal of orofacial orthopedics = Fortschritte der Kieferorthopadie : Organ/official journal Deutsche Gesellschaft fur Kieferorthopadie}, volume = {70}, number = {2}, pages = {139-151}, pmid = {19322532}, issn = {1615-6714}, mesh = {Adolescent ; Anodontia/*epidemiology/*pathology ; Cephalometry/statistics & numerical data ; Child ; Facial Bones/*anatomy & histology ; Female ; Germany/epidemiology ; Humans ; Male ; Maxillofacial Development ; Skull/*pathology ; }, abstract = {OBJECTIVE: Aim of this study was to investigate any correlations between the congenital absence of certain permanent teeth and individual craniofacial growth patterns.

MATERIAL AND METHODS: The lateral cephalograms of n = 101 patients (65 female und 36 male) with various congenitally missing teeth were analyzed according to Hasund [11] prior to orthodontic treatment. Cephalometric data to determine the craniofacial growth pattern comprised GntgoAr, NSBa, ML-NSL, NL-NSL, MLNL angles and the index between upper and lower facial heights. Correlations between the type of missing teeth and growth pattern were examined. Group distribution was A = all patients with missing teeth (n = 101), P = missing second premolars (n = 49), S = missing upper lateral incisors (n = 30), X = various missing teeth (n = 22). We included a control group for each of these groups using data from Riolo et al.'s [22] growth study.

RESULTS: Group A revealed an even distribution with n = 32 patients (31.7%) having a vertical growth pattern, n = 37 patients (36.6%) a neutral growth pattern, and n = 32 patients (31.7%) a horizontal growth pattern. The majority of patients (n = 20, 40.8%) in group P exhibited a horizontal growth pattern, whereas there were no significant correlations between the kind of congenitally missing teeth and growth patterns in groups S and X. Comparison of the mean values of groups P, S and X, revealed no significant differences. When comparing the control group to groups A, P and S, we noted significantly or highly significantly smaller gonial and basal plane angles. No significant differences were apparent concerning group X.

CONCLUSIONS: This examination demonstrates no statistically-relevant correlation between craniofacial growth pattern and the congenital absence of certain permanent teeth, although horizontal growth is more frequent (but not significant) in patients with congenitally missing second premolars.}, } @article {pmid19304620, year = {2009}, author = {Folk, CL and Remington, RW and Wu, SC}, title = {Additivity of abrupt onset effects supports nonspatial distraction, not the capture of spatial attention.}, journal = {Attention, perception & psychophysics}, volume = {71}, number = {2}, pages = {308-313}, doi = {10.3758/APP.71.2.308}, pmid = {19304620}, issn = {1943-3921}, mesh = {*Attention ; *Color Perception ; *Cues ; Discrimination, Psychological ; Humans ; *Orientation ; *Pattern Recognition, Visual ; Reaction Time ; }, abstract = {In a recent article, Schreij, Owens, and Theeuwes (2008) reported that abruptly onsetting distractors produce costs in performance even when spatial-cuing effects confirm the presence of a top-down set for color. The authors argued that these results show that abruptly onsetting new objects capture attention independent of a top-down set and, thus, provide conclusive evidence against the theory that attentional capture is contingent on top-down attentional control settings (Folk, Remington, & Johnston, 1992). In the following article, we argue that, contrary to the conclusion drawn by Schreij et al., their own data (1) disconfirm the claim that their abrupt onsets captured spatial attention and (2) are consistent with nonspatial interference accounts of singleton-distractor effects. In support of the nonspatial account, we show that in a paradigm similar to Schreij et al.'s, distractors that do not capture attention can nonetheless influence responses to a target. We conclude that the results of Schreij et al. do not represent a challenge to contingent capture theory.}, } @article {pmid19302406, year = {2009}, author = {Yap, JS and Fan, J and Wu, R}, title = {Nonparametric modeling of longitudinal covariance structure in functional mapping of quantitative trait loci.}, journal = {Biometrics}, volume = {65}, number = {4}, pages = {1068-1077}, pmid = {19302406}, issn = {1541-0420}, support = {R01 GM072611/GM/NIGMS NIH HHS/United States ; R01-GM072611/GM/NIGMS NIH HHS/United States ; NIGMS-0540745//PHS HHS/United States ; }, mesh = {Animals ; Biometry/*methods ; Chromosome Mapping/statistics & numerical data ; Computer Simulation ; Databases, Genetic ; Female ; Genome-Wide Association Study/statistics & numerical data ; Likelihood Functions ; Male ; Mice ; *Models, Statistical ; Multivariate Analysis ; *Quantitative Trait Loci ; *Statistics, Nonparametric ; }, abstract = {Estimation of the covariance structure of longitudinal processes is a fundamental prerequisite for the practical deployment of functional mapping designed to study the genetic regulation and network of quantitative variation in dynamic complex traits. We present a nonparametric approach for estimating the covariance structure of a quantitative trait measured repeatedly at a series of time points. Specifically, we adopt Huang et al.'s (2006, Biometrika 93, 85-98) approach of invoking the modified Cholesky decomposition and converting the problem into modeling a sequence of regressions of responses. A regularized covariance estimator is obtained using a normal penalized likelihood with an L(2) penalty. This approach, embedded within a mixture likelihood framework, leads to enhanced accuracy, precision, and flexibility of functional mapping while preserving its biological relevance. Simulation studies are performed to reveal the statistical properties and advantages of the proposed method. A real example from a mouse genome project is analyzed to illustrate the utilization of the methodology. The new method will provide a useful tool for genome-wide scanning for the existence and distribution of quantitative trait loci underlying a dynamic trait important to agriculture, biology, and health sciences.}, } @article {pmid19302278, year = {2009}, author = {Munro, E}, title = {Managing societal and institutional risk in child protection.}, journal = {Risk analysis : an official publication of the Society for Risk Analysis}, volume = {29}, number = {7}, pages = {1015-1023}, doi = {10.1111/j.1539-6924.2009.01204.x}, pmid = {19302278}, issn = {1539-6924}, mesh = {Child ; Child Abuse/*prevention & control ; Cooperative Behavior ; Humans ; *Public Sector ; Risk Factors ; *Risk Management ; *Social Environment ; *Social Work ; }, abstract = {Public sector services have been reshaped by two interacting factors: the growing dominance of risk management and the growing demands for transparency and accountability. For the caring professions, these have provoked radical reform. Using the child protection service as a case study, this article explores the impact of the changes on a service that deals with conflicting risks and has a poorly articulated knowledge base. Drawing on Rothstein et al.'s distinction between societal and institutional risks, it is argued that difficulties in managing societal risks are creating serious institutional risks. The latter are then being prioritized in the way the system operates. The preoccupation with such risks has been translated into concerted efforts to formalize the work of front line practitioners to make it transparent and auditable. Although done, in part, with the good intention of spreading good practice standards, this formalization has gone beyond the evidenced knowledge base to the extent that it is creating a new picture of "good practice" that omits significant dimensions of work and is distinct from measures of children's safety or welfare. Moreover, the process of formalization acts as an impediment to knowledge development in disciplines where such learning is urgently needed.}, } @article {pmid19290014, year = {2009}, author = {Mojtahedi, MC and Valentine, RJ and Evans, EM}, title = {Body composition assessment in athletes with spinal cord injury: comparison of field methods with dual-energy X-ray absorptiometry.}, journal = {Spinal cord}, volume = {47}, number = {9}, pages = {698-704}, doi = {10.1038/sc.2009.20}, pmid = {19290014}, issn = {1476-5624}, mesh = {Absorptiometry, Photon/*methods ; Adolescent ; Adult ; Anthropometry/*methods ; Athletic Injuries/complications ; Body Composition/*physiology ; Electric Impedance ; Female ; Humans ; Male ; Sex Factors ; Skinfold Thickness ; Spinal Cord Injuries/*diagnosis/etiology ; Sports ; Statistics as Topic ; Young Adult ; }, abstract = {STUDY DESIGN: Cross-sectional.

OBJECTIVES: To compare relative body fatness (%Fat) estimates from field methods (skinfold thickness measurement (SKF) and bioelectrical impedance analysis (BIA)) with measures by dual-energy X-ray absorptiometry (DXA).

SETTING: University of Illinois, Urbana-Champaign, IL, USA.

METHODS: Field methods used both three- and seven-site SKF prediction equations and BIA generalized, spinal cord injury (SCI)-specific and athlete-specific equations. DXA was used as the reference method. College-aged varsity athletes with SCI (women=8, men=8; time since injury 16.2+/-5.7 years; injury level range T5-L5) were recruited.

RESULTS: Mean BMI was 20.8+/-2.6 and 22.5+/-2.1 kg m(-2), and mean DXA %Fat was 31.9+/-3.8 and 20.6+/-8.4%, for women and men, respectively. All field methods under-predicted the %Fat when compared with DXA (ranges in mean differences: SKF women 2.9-8.2%, SKF men 6.9-12.4%; BIA women 0.5-3.9%, BIA men 0.3-7.0%). None of the field methods accurately predicted the %Fat compared with DXA (total error (TE): SKF women 7.4-12.1%, SKF men 8.4-15.2%; BIA women 5.1-9.3%, BIA men 6.7-10.7%). Of the SKF and BIA prediction equations, Evans et al.'s three-site SKF (r=0.95, P<0.001, standard error of the estimate (SEE)=2.8 %Fat) prediction equation provided the best fit for this population.

CONCLUSION: Further studies with larger samples are necessary to develop appropriate prediction equations for field methods in the athletic SCI population.}, } @article {pmid19289722, year = {2009}, author = {Murphy, RJ and Gray, SA and Sterling, G and Reeves, K and DuCette, J}, title = {A comparative study of professional student stress.}, journal = {Journal of dental education}, volume = {73}, number = {3}, pages = {328-337}, pmid = {19289722}, issn = {1930-7837}, mesh = {Achievement ; Career Choice ; Educational Measurement ; Faculty, Dental ; Faculty, Medical ; Feedback, Psychological ; Female ; Humans ; Interpersonal Relations ; Male ; Professional-Patient Relations ; Self Concept ; Sex Factors ; Stress, Physiological/*physiology ; Stress, Psychological/*physiopathology ; *Students, Dental/psychology ; *Students, Medical/psychology ; }, abstract = {A study was conducted involving a group of 290 medical and dental students to directly compare perceived stress levels encountered during their education. A modified questionnaire based on Garbee et al.'s Dental Environmental Stress survey was provided to the students by either email or paper. The purpose of the investigation was to determine if the sources of stress reported by medical and dental students, both male and female, were due to common factors. A multivariate statistical analysis was also conducted to measure stress differences by year in school. Through factor analysis, the survey question responses were grouped into five causal categories: academic performance, faculty relations, patient and clinic responsibilities, personal life issues, and professional identity. The overall findings show that dental students had greater levels of stress than medical students in three of the five categories. The only category in which medical students demonstrated greater stress levels than dental students was in professional identity. Measures of comparative levels of stress between male and female students for either profession did not demonstrate any significant differences. Stress levels related to clinical work varied significantly between the type of professional student and his or her year in school.}, } @article {pmid19269795, year = {2009}, author = {Broich, K and , }, title = {Committee for Medicinal Products for Human Use (CHMP) assessment on efficacy of antidepressants.}, journal = {European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology}, volume = {19}, number = {5}, pages = {305-308}, doi = {10.1016/j.euroneuro.2009.01.012}, pmid = {19269795}, issn = {1873-7862}, mesh = {Antidepressive Agents/*therapeutic use ; Depressive Disorder, Major/*drug therapy ; Drug Approval/*organization & administration ; *Drug Evaluation/methods/standards ; Europe ; Federal Government ; Humans ; Meta-Analysis as Topic ; }, abstract = {BACKGROUND: Recent publications have raised questions over the efficacy and clinically relevant effects of antidepressants that have been approved for the treatment of major depression. In this context, the European Commission requested that the European Medicines Agency (EMEA) and its scientific committee (CHMP) issue an opinion on these data under Article 5(3) of Regulation (EC) No 726/2004.

FINDINGS: Results from a recent meta-analysis [Kirsch, I., Deacon, B.J. et al., (2008) Initial severity and antidepressant benefits: a meta-analysis of data submitted to the Food and Drug Administration. PLoS Med. 5(2), e45.] have questioned the clinical relevance of the use of some antidepressants in treating major depression. This analysis focused only on statistically significant mean differences versus placebo in changes in a rating scale (such as the Hamilton Depression Rating Scale). This, however, would not be an adequate basis for the evaluation of clinical relevance and, from a regulatory perspective, would not be sufficient to grant an antidepressant the approval needed to allow it onto the market. Improvements that are both statistically significant (based on improvements in validated rating scales between baseline and study end) and clinically relevant (based on responder rates) need to be shown in short-term studies. In addition, these short-term results need to be confirmed in a randomised withdrawal study to demonstrate the maintenance of an antidepressant's effects.

CONCLUSIONS: The CHMP concluded that the approval of antidepressants for the treatment of patients with major depression is based on data that provide robust and sufficient evidence of clinically meaningful benefits for patients with major depression. Therefore, the CHMP is of the opinion that, as no public health concerns have been identified, no regulatory action is necessary on the basis of Kirsch et al.'s findings.}, } @article {pmid19262586, year = {2009}, author = {Sampaio, C}, title = {Can focusing on UPDRS Part II make assessments of Parkinson disease progression more efficient?.}, journal = {Nature clinical practice. Neurology}, volume = {5}, number = {3}, pages = {130-131}, pmid = {19262586}, issn = {1745-8358}, abstract = {Harrison et al. have attempted to validate Part II of the Unified Parkinson's Disease Rating Scale (UPDRS II) as a medication-independent measure of disease progression. The authors collected cross-sectional data from a cohort of 888 patients with idiopathic Parkinson disease, and they found a robust association between UPDRS II scores and disease duration. Other variables considered were the patients' levodopa status, age at disease onset, and scores on UPDRS I, II and III. The results suggest that a single UPDRS II measurement might be a good indicator of progression at a given time point, irrespective of the current disease-related circumstances. This concept is attractive in its simplicity and patient-centeredness. However, this evidence came from a single-center, retrospective study, the statistical model was constructed using a nonvalidated surrogate as an independent variable, and no external replication was conducted. Until further confirmation, therefore, Harrison et al.'s proposal can only be considered to be a working hypothesis.}, } @article {pmid19258982, year = {2009}, author = {Hoftman, NN and Ferrante, FM}, title = {Diagnosis of unintentional subdural anesthesia/analgesia: analyzing radiographically proven cases to define the clinical entity and to develop a diagnostic algorithm.}, journal = {Regional anesthesia and pain medicine}, volume = {34}, number = {1}, pages = {12-16}, doi = {10.1097/AAP.0b013e31819339cf}, pmid = {19258982}, issn = {1532-8651}, mesh = {*Algorithms ; Analgesia, Epidural/*adverse effects ; Anesthesia, Epidural/*adverse effects ; Catheters, Indwelling/adverse effects ; Hemodynamics ; Humans ; Injections, Epidural/adverse effects ; Intraoperative Complications/*diagnostic imaging/etiology/physiopathology ; Motor Neurons ; Nerve Block/*adverse effects ; Predictive Value of Tests ; Radiography ; Respiratory Mechanics ; Risk Assessment ; Risk Factors ; Subdural Space/*diagnostic imaging ; }, abstract = {BACKGROUND AND OBJECTIVES: : Subdural injection is a well-known but often poorly recognized complication of neuraxial anesthesia/analgesia. This report aims to further describe the clinical presentation of subdural injection by analyzing radiographically proven cases. A new diagnostic algorithm is then proposed.

METHODS: : A literature search identified 70 radiographically confirmed cases of subdural injection. The prevalence of numerous presenting characteristics and their relationship to the volume of injected local anesthetics were examined. The ability of 2 previously published diagnostic paradigms to detect proven subdural injection was compared with that of a newly proposed algorithm.

RESULTS: : The dermatomal distribution of sensory blockade was excessive in 74% of cases, restricted in 17%, and neither in 9%. Motor blockade and respiratory depression were associated with larger local anesthetic injection volumes (median volume = 14 vs. 8 mL [P <.009] and 15 vs. 10 mL [P <.035], respectively), but segmental spread and cardiovascular depression were not. Only 33% of cases were positive for 2 or more of Collier's criteria; Lubenow et al.'s diagnostic paradigm detected 71% of cases. We propose a diagnostic algorithm structured as a "roadmap," whereby the clinician inputs the assumed neuraxial block (epidural vs. subarachnoid), and distribution of sensory blockade (excessive, restricted, neither). Specific minor criteria are then applied to diagnose subdural injections. This algorithm detected 93% of subdurals with excessive sensory block distribution, and all of those with restricted and normal distribution.

CONCLUSIONS: : Radiographically proven subdural injections were used to further define the clinical presentation of subdural analgesia/analgesia and a new diagnostic algorithm is proposed.}, } @article {pmid19245400, year = {2009}, author = {Biziulevicius, GA and Kazlauskaite, J}, title = {Bacterial cell wall hydrolases as novel alternatives to antibiotics: a critical comment on Parisien et al.'s (2008) interpretation of the topic.}, journal = {Journal of applied microbiology}, volume = {106}, number = {5}, pages = {1752-3; author reply 1754-9}, doi = {10.1111/j.1365-2672.2009.04253.x}, pmid = {19245400}, issn = {1365-2672}, mesh = {Anti-Bacterial Agents/*pharmacology ; Antimicrobial Cationic Peptides/therapeutic use ; Bacterial Infections/*therapy ; Cell Wall/*enzymology ; Hydrolases/*therapeutic use ; }, } @article {pmid19244642, year = {2008}, author = {Loh, PS and Miller, AE and Reeves, AD and Harvey, SM and Overnell, J}, title = {Optimised recovery of lignin-derived phenols in a Scottish fjord by the CuO oxidation method.}, journal = {Journal of environmental monitoring : JEM}, volume = {10}, number = {10}, pages = {1187-1194}, doi = {10.1039/b808970a}, pmid = {19244642}, issn = {1464-0325}, mesh = {Copper/*chemistry ; Environmental Monitoring/*methods ; Geologic Sediments/*chemistry ; Lignin/*analysis ; Oxidation-Reduction ; Phenols/*analysis ; Scotland ; Seasons ; Water/*chemistry ; }, abstract = {Lignin is found only in vascular plant tissues, hence monitoring of lignin in aquatic environments is important in the determination of the sources and fate of terrestrial organic matter (OM). Concentrations of lignin-derived phenols provide an estimate of the amount of terrestrial OM in a system. Other lignin parameters such as the ratios of syringyl to vanillyl (S/V) and cinnamyl to vanillyl (C/V) phenols provide information on vegetation sources; and the ratios of vanillic acid to vanillin, (Ad/Al)v, and syringic acid to syringaldehyde, (Ad/Al)s, indicate the degradation stage of lignin materials. Concentrations of lignin-derived phenols were determined for the surface and subsurface sediments of a Scottish sea loch, Loch Creran, using a CuO oxidation method. In order to achieve the highest methodological efficiency, a series of validation experiments for each procedural step were carried out. As a result, several procedural steps were optimized. It was found that a lower oxidation temperature resulted in higher product yield and the duration and temperature of the silylation step have no effect on the outcome of the process. Studies of seasonal variations of lignin parameters showed that the occasional increase in lignin content in sediment trap samples was attributable to materials discharged from River Creran and the incoming water from the direction of Creagan bridge. The flow regime caused resuspension of surface sediments and entrainment of lignin materials into the water column. Lignin parameters exhibited more significant trends across an axial transect of the loch (from the head to mouth). Total lignin content decreased and the C/V ratios increased from upper to lower Loch Creran as these lignin materials were transported further down the loch and were subjected to hydrodynamic sorting processes.}, } @article {pmid19243534, year = {2009}, author = {Cox, LA}, title = {Improving risk-based decision making for terrorism applications.}, journal = {Risk analysis : an official publication of the Society for Risk Analysis}, volume = {29}, number = {3}, pages = {336-41; discussion 342-3}, doi = {10.1111/j.1539-6924.2009.01206.x}, pmid = {19243534}, issn = {1539-6924}, mesh = {*Decision Making ; Humans ; *Risk ; Risk Reduction Behavior ; Terrorism/*prevention & control ; Uncertainty ; }, abstract = {How can we best allocate limited defensive resources to reduce terrorism risks? Dillon et al.'s Antiterrorism Risk-Based Decision Aid (ARDA) system provides a useful point of departure for addressing this crucial question by exhibiting a real-world system that calculates risk reduction scores for different portfolios of risk-reducing countermeasures and using them to rank-order different possible risk mitigation alternatives for Navy facilities. This comment points out some potential limitations of any scoring system that does not take into account risk externalities, interdependencies among threats, uncertainties that are correlated across targets, and attacker responses to alternative allocations of defensive resources. In at least some simple situations, allocations based on risk reduction scores and comparisons can inadvertently increase risks by providing intelligent attackers with valuable information, or they can fail to reduce risks as effectively as nonscoring, optimization-based approaches. These limitations of present scoring methods present exciting technical challenges and opportunities for risk analysts to develop improved methods for protecting facilities and infrastructure against terrorist threats.}, } @article {pmid19231478, year = {2009}, author = {Jordan, TR and Paterson, KB and Stachurski, M}, title = {Re-evaluating split-fovea processing in word recognition: effects of word length.}, journal = {Cortex; a journal devoted to the study of the nervous system and behavior}, volume = {45}, number = {4}, pages = {495-505}, doi = {10.1016/j.cortex.2007.07.007}, pmid = {19231478}, issn = {0010-9452}, support = {059727//Wellcome Trust/United Kingdom ; }, mesh = {Analysis of Variance ; Discrimination, Psychological/physiology ; Eye Movements/physiology ; Fixation, Ocular/*physiology ; Fovea Centralis/*physiology ; Functional Laterality/*physiology ; Humans ; Pattern Recognition, Visual/physiology ; *Reading ; Recognition, Psychology/*physiology ; Reference Values ; Verbal Behavior/physiology ; Vision, Ocular/physiology ; Visual Fields/*physiology ; Visual Perception/physiology ; Vocabulary ; }, abstract = {Several studies have claimed that, when fixating a word, letters to the left and right of fixation project to different hemispheres and are consequently subjected to different processes. In support of this claim, Lavidor M, et al. (2001; hereafter LES&B) report that lexical decisions were affected by increasing the number of letters to the left of fixation but not to the right, and that this indicates divided hemispheric access at the point of fixation to length-sensitive processes in the right hemisphere (RH). We re-evaluated these claims in Experiment 1 using Lavidor et al.'s original stimuli and procedure of merely instructing participants where to fixate. In contrast to the earlier study, increases in the number of letters to the left and right of the designated fixation location produced near-identical effects on reaction time, and increases to the left actually improved response accuracy and increases to the right impaired it. When larger stimuli were used to improve stimulus perceptibility and an eye-tracker monitored fixation accuracy (Experiment 2), left and right increases in the number of letters again produced near-identical effects on reaction time (and accuracy), but frequent and substantial fixation errors were revealed. When an eye-tracker ensured accurate fixations (Experiment 3), left and right increases in the number of letters again produced near-identical effects on reaction time and accuracy. Thus, the findings of all three experiments provide no support for the findings of LES&B (2001) and no evidence of split-fovea processing. The findings also indicate the dangers of assuming fixation of precisely-specified locations within words, both in experiments designed to reveal split-foveal processing and hemispheric asymmetry and in more normal circumstances of word perception.}, } @article {pmid19228377, year = {2009}, author = {Ren, J and Liu, X and Zhang, G and Liu, B and Guo, X}, title = {"Tandem duplication-random loss" is not a real feature of oyster mitochondrial genomes.}, journal = {BMC genomics}, volume = {10}, number = {}, pages = {84}, pmid = {19228377}, issn = {1471-2164}, mesh = {Animals ; Crassostrea/*genetics ; DNA Primers/genetics ; DNA, Mitochondrial/genetics ; *Gene Deletion ; *Gene Duplication ; Gene Order ; *Genome, Mitochondrial ; Polymorphism, Single Nucleotide ; RNA, Ribosomal/genetics ; RNA, Transfer/genetics ; Sequence Analysis, DNA ; Species Specificity ; }, abstract = {Duplications and rearrangements of coding genes are major themes in the evolution of mitochondrial genomes, bearing important consequences in the function of mitochondria and the fitness of organisms. Yu et al. (BMC Genomics 2008, 9:477) reported the complete mt genome sequence of the oyster Crassostrea hongkongensis (16,475 bp) and found that a DNA segment containing four tRNA genes (trnK(1), trnC, trnQ(1) and trnN), a duplicated (rrnS) and a split rRNA gene (rrnL5') was absent compared with that of two other Crassostrea species. It was suggested that the absence was a novel case of "tandem duplication-random loss" with evolutionary significance. We independently sequenced the complete mt genome of three C. hongkongensis individuals, all of which were 18,622 bp and contained the segment that was missing in Yu et al.'s sequence. Further, we designed primers, verified sequences and demonstrated that the sequence loss in Yu et al.'s study was an artifact caused by placing primers in a duplicated region. The duplication and split of ribosomal RNA genes are unique for Crassostrea oysters and not lost in C. hongkongensis. Our study highlights the need for caution when amplifying and sequencing through duplicated regions of the genome.}, } @article {pmid19224643, year = {2009}, author = {Zuyderduyn, SD}, title = {Correspondence regarding "Effect of active smoking on the human bronchial epithelium transcriptome".}, journal = {BMC genomics}, volume = {10}, number = {}, pages = {82}, pmid = {19224643}, issn = {1471-2164}, mesh = {Bronchi/*metabolism ; Epithelium/metabolism ; False Positive Reactions ; Gene Expression ; Gene Expression Profiling ; Humans ; RNA, Messenger/genetics ; Smoking/*genetics/metabolism ; Smoking Cessation ; }, abstract = {BACKGROUND: In the work of Chari et al. entitled "Effect of active smoking on the human bronchial epithelium transcriptome" the authors use SAGE to identify candidate gene expression changes in bronchial brushings from never, former, and current smokers. These gene expression changes are categorized into those that are reversible or irreversible upon smoking cessation. A subset of these identified genes is validated on an independent cohort using RT-PCR. The authors conclude that their results support the notion of gene expression changes in the lungs of smokers which persist even after an individual has quit.

RESULTS: This correspondence raises questions about the validity of the approach used by the authors to analyze their data. The majority of the reported results suffer deficiencies due to the methods used. The most fundamental of these are explained in detail: biases introduced during data processing, lack of correction for multiple testing, and an incorrect use of clustering for gene discovery. A randomly generated "null" dataset is used to show the consequences of these shortcomings.

CONCLUSION: Most of Chari et al.'s findings are consistent with what would be expected by chance alone. Although there is clear evidence of reversible changes in gene expression, the majority of those identified appear to be false positives. However, contrary to the authors' claims, no irreversible changes were identified. There is a broad consensus that genetic change due to smoking persists once an individual has quit smoking; unfortunately, this study lacks sufficient scientific rigour to support or refute this hypothesis or identify any specific candidate genes. The pitfalls of large-scale analysis, as exemplified here, may not be unique to Chari et al.}, } @article {pmid19210030, year = {2009}, author = {Rohling, ML and Faust, ME and Beverly, B and Demakis, G}, title = {Effectiveness of cognitive rehabilitation following acquired brain injury: a meta-analytic re-examination of Cicerone et al.'s (2000, 2005) systematic reviews.}, journal = {Neuropsychology}, volume = {23}, number = {1}, pages = {20-39}, doi = {10.1037/a0013659}, pmid = {19210030}, issn = {0894-4105}, mesh = {Brain Injuries/*complications ; Cognition Disorders/*etiology/*rehabilitation ; Humans ; Neuropsychological Tests ; *Outcome Assessment, Health Care ; PubMed/statistics & numerical data ; }, abstract = {The present study provides a meta-analysis of cognitive rehabilitation literature (K = 115, N = 2,014) that was originally reviewed by K. D. Cicerone et al. (2000, 2005) for the purpose of providing evidence-based practice guidelines for persons with acquired brain injury. The analysis yielded a small treatment effect size (ES = .30, d(+) statistic) directly attributable to cognitive rehabilitation. A larger treatment effect (ES = .71) was found for single-group pretest to posttest outcomes; however, modest improvement was observed for nontreatment control groups as well (ES = .41). Correction for this effect, which was not attributable to cognitive treatments, resulted in the small, but significant, overall estimate. Treatment effects were moderated by cognitive domain treated, time postinjury, type of brain injury, and age. The meta-analysis revealed sufficient evidence for the effectiveness of attention training after traumatic brain injury and of language and visuospatial training for aphasia and neglect syndromes after stroke. Results provide important quantitative documentation of effective treatments, complementing recent systematic reviews. Findings also highlight gaps in the scientific evidence supporting cognitive rehabilitation, thereby indicating future research directions.}, } @article {pmid19208287, year = {2009}, author = {Towns, AJ and Adams, PJ}, title = {Staying quiet or getting out: some ideological dilemmas faced by women who experience violence from male partners.}, journal = {The British journal of social psychology}, volume = {48}, number = {Pt 4}, pages = {735-754}, doi = {10.1348/014466608X398762}, pmid = {19208287}, issn = {0144-6665}, mesh = {*Conflict, Psychological ; Cultural Characteristics ; Family Characteristics ; Female ; Femininity ; Humans ; Individuality ; Interviews as Topic ; Male ; *Psychology, Social ; *Self Disclosure ; Self-Help Groups ; Social Identification ; Spouse Abuse/*psychology ; }, abstract = {Violence against women by men who are their intimate partners is now recognized internationally as a significant problem and one that impacts on social and community development and on the health of women and children. Women commonly report little of this violence. In this paper, we discuss the various socially constructed dilemmas for women that may silence them from talking of such violence. Billig et al.'s (1988) concept of ideological dilemmas emerged as a useful analytic device from which to analyse the discourses of 20 women who had experienced violence from their male partners. In particular, the influence of ideologies of patriarchy and of equity, and ideologies of individualism and collectivism were found to impact on some women's talk of such violence. This research contributes to the current debate on the psychosocial by describing the ways in which ideological dilemmas interweave across the social and the psychological.}, } @article {pmid19203431, year = {2009}, author = {Lanting, S and Haugrud, N and Crossley, M}, title = {The effect of age and sex on clustering and switching during speeded verbal fluency tasks.}, journal = {Journal of the International Neuropsychological Society : JINS}, volume = {15}, number = {2}, pages = {196-204}, doi = {10.1017/S1355617709090237}, pmid = {19203431}, issn = {1469-7661}, mesh = {Adult ; Aged ; Aging/*physiology ; Attention/*physiology ; *Cluster Analysis ; Female ; Humans ; *Language ; Male ; Neuropsychological Tests ; Photic Stimulation/methods ; *Sex Characteristics ; Verbal Behavior/*physiology ; Young Adult ; }, abstract = {Past research has been inconsistent with regard to the effects of normal aging and sex on strategy use during verbal fluency performance. In the present study, both Troyer et al.'s (1997) and Abwender et al.'s (2001) scoring methods were used to measure switching and clustering strategies in 60 young and 72 older adults, equated on verbal ability. Young adults produced more words overall and switched more often during both phonemic and semantic fluency tasks, but performed similarly to older adults on measures of clustering. Although there were no sex differences in total words produced on either fluency task, males produced larger clusters on both tasks, and females switched more frequently than males on the semantic but not on the phonemic fluency task. Although clustering strategies appear to be relatively age-insensitive, age-related changes in switching strategies resulted in fewer overall words produced by older adults. This study provides evidence of age and sex differences in strategy use during verbal fluency tests, and illustrates the utility of combining Troyer's and Abwender's scoring procedures with in-depth categorization of clustering to understand interactions between age and sex during semantic fluency tasks.}, } @article {pmid19201610, year = {2009}, author = {Silsupadol, P and Lugade, V and Shumway-Cook, A and van Donkelaar, P and Chou, LS and Mayr, U and Woollacott, MH}, title = {Training-related changes in dual-task walking performance of elderly persons with balance impairment: a double-blind, randomized controlled trial.}, journal = {Gait & posture}, volume = {29}, number = {4}, pages = {634-639}, pmid = {19201610}, issn = {1879-2219}, support = {R01 AG021598/AG/NIA NIH HHS/United States ; AG-021598/AG/NIA NIH HHS/United States ; }, mesh = {Accidental Falls/prevention & control/statistics & numerical data ; Aged ; Aging/*physiology ; Analysis of Variance ; Double-Blind Method ; Female ; Geriatric Assessment ; Humans ; Male ; Postural Balance/*physiology ; Task Performance and Analysis ; Treatment Outcome ; Walking/*physiology ; }, abstract = {The purpose of this study was to compare the efficiency of three different balance training strategies in an effort to understand the mechanisms underlying training-related changes in dual-task balance performance of older adults with balance impairment. Elderly individuals with balance impairment, age 65 and older, were randomly assigned to one of three individualized training programs: single-task (ST) balance training; dual-task training with fixed-priority (FP) instruction; and dual-task training with variable-priority (VP) instruction. Balance control during gait, under practiced and novel conditions, was assessed by calculating the center of mass and ankle joint center inclination angles in the frontal plane. A smaller angle indicated better balance performance. Other outcomes included gait velocity, stride length, verbal reaction time, and rate of response. All measures were collected at baseline and the end of the 4-week training. Results indicated that all training strategies were equally effective (P>.05) at improving balance performance (smaller inclination angle) under single-task contexts. However, the VP training strategy was more effective (P=.04) in improving both balance and cognitive performance under dual-task conditions than either the ST or the FP training strategies. Improved dual-task processing skills did not transfer to a novel dual-task condition. Results support Kramer et al.'s proposal that VP training improves both single-task automatization and the development of task-coordination skills.}, } @article {pmid19198777, year = {2009}, author = {Exley, C}, title = {Silicon in life: whither biological silicification?.}, journal = {Progress in molecular and subcellular biology}, volume = {47}, number = {}, pages = {173-184}, doi = {10.1007/978-3-540-88552-8_7}, pmid = {19198777}, issn = {0079-6484}, mesh = {Diatoms/metabolism ; Homeostasis ; Selection, Genetic ; Silicic Acid/metabolism ; Silicon/*metabolism ; }, abstract = {In my opinion, the last decade or so has seen a golden era of research into the many facets of biological silicification. The contents of this volume are testimony to recent advances in the field (Müller and Grachev 2008). The successes should be carried through into the next 10 years during which time the processes involved in the biomineralisation of silica ought to become as well understood as they are for calcium and iron-based biominerals. Of course, the reason why progress in biological silicification has been relatively slow is an apparent lack of appropriate chemistry to explain myriad forms of seemingly diverse examples of the deposition of silica in biota. In this Chapter, the title of which is a paraphrase of Voronkov et al.'s great work, Silicon and Life (1975), I have tried to provide plau sible bioinorganic solutions to biological silicification. Ideas are presented in the context of the evolution of biological silicification and are discussed, in the main, naively without specific reference to published research which might either refute or support their validity. (This serves as an apology to the many excellent scientists whose work has not been but should have been cited!) I hope the ideas presented herein demonstrate that, rather than acting as a barrier to understanding biologi cal silicification, the limited, biologically significant, chemistry of silicic acid is actually sufficient to act as a platform for future research in the field.}, } @article {pmid21172249, year = {2009}, author = {Ferrante, M and Vermeire, S and Van Assche, G and Rutgeerts, P}, title = {Reply to Dr. Caprilli et al.'s letter.}, journal = {Journal of Crohn's & colitis}, volume = {3}, number = {1}, pages = {45}, doi = {10.1016/j.crohns.2008.11.001}, pmid = {21172249}, issn = {1876-4479}, } @article {pmid19174766, year = {2009}, author = {Maconi, G and Porro, GB}, title = {Combining two imaging techniques is best to diagnose small-bowel Crohn's disease.}, journal = {Nature clinical practice. Gastroenterology & hepatology}, volume = {6}, number = {3}, pages = {142-143}, pmid = {19174766}, issn = {1743-4386}, abstract = {In most patients with Crohn's disease, diagnostic gastrointestinal lesions are located in the small bowel, which is not easily accessible to direct investigation. This commentary focuses on an article by Solem et al., which compared the utility of four primary small-bowel imaging modalities (CT enterography, ileocolonoscopy, capsule endoscopy, and small-bowel follow-through) in diagnosis of active small-bowel Crohn's disease. Capsule endoscopy had lower diagnostic specificity than the other techniques. This result, in conjunction with the need to perform preliminary small-bowel radiography to detect asymptomatic, partial, small-bowel obstructions, makes capsule endoscopy a poor choice as a first-line test for Crohn's disease. We concur with Solem et al.'s opinion that a combination of two of the other available imaging methods is the best diagnostic option for small-bowel Crohn's disease, although the choice of which two to use should be based on the facilities and expertise that are available locally.}, } @article {pmid19169358, year = {2009}, author = {Joppa, LN and Loarie, SR and Pimm, SL}, title = {On population growth near protected areas.}, journal = {PloS one}, volume = {4}, number = {1}, pages = {e4279}, pmid = {19169358}, issn = {1932-6203}, mesh = {*Biodiversity ; Conservation of Natural Resources/economics/legislation & jurisprudence ; Ecology ; Ecosystem ; Geography ; Humans ; Models, Theoretical ; Population ; Population Density ; Population Dynamics ; Population Growth ; Zambia ; }, abstract = {BACKGROUND: Protected areas are the first, and often only, line of defense in efforts to conserve biodiversity. They might be detrimental or beneficial to rural communities depending on how they alter economic opportunities and access to natural resources. As such, protected areas may attract or repel human settlement. Disproportionate increases in population growth near protected area boundaries may threaten their ability to conserve biodiversity.

Using decadal population datasets, we analyze population growth across 45 countries and 304 protected areas. We find no evidence for population growth near protected areas to be greater than growth of rural areas in the same country. Furthermore, we argue that what growth does occur near protected areas likely results from a general expansion of nearby population centers.

CONCLUSIONS/SIGNIFICANCE: Our results contradict those from a recent study by Wittemyer et al., who claim overwhelming evidence for increased human population growth near protected areas. To understand the disagreement, we re-analyzed the protected areas in Wittemyer et al.'s paper. Their results are simply artifacts of mixing two incompatible datasets. Protected areas may experience unusual population pressures near their edges; indeed, individual case studies provide examples. There is no evidence, however, of a general pattern of disproportionate population growth near protected areas.}, } @article {pmid19167834, year = {2009}, author = {Wu, R and Zeng, Y}, title = {Comment on Shi et al.'s hypothesis: survivin will go much further.}, journal = {Medical hypotheses}, volume = {72}, number = {3}, pages = {363}, doi = {10.1016/j.mehy.2008.10.016}, pmid = {19167834}, issn = {0306-9877}, mesh = {Genetic Therapy ; Genetic Vectors ; Humans ; Inhibitor of Apoptosis Proteins ; Microtubule-Associated Proteins/*antagonists & inhibitors/*genetics ; Models, Biological ; Neoplasms/*radiotherapy ; RNA Interference ; Radiation Tolerance ; Survivin ; Transfection ; }, } @article {pmid19157075, year = {2009}, author = {Wefald, AJ and Downey, RG}, title = {Construct dimensionality of engagement and its relation with satisfaction.}, journal = {The Journal of psychology}, volume = {143}, number = {1}, pages = {91-111}, doi = {10.3200/JRLP.143.1.91-112}, pmid = {19157075}, issn = {0022-3980}, mesh = {*Achievement ; Adult ; *Affect ; Female ; Humans ; Industry ; Male ; Middle Aged ; Motivation ; *Personal Satisfaction ; Surveys and Questionnaires ; Young Adult ; }, abstract = {Engagement--a persistent and positive affective-motivational state of fulfillment characterized by vigor, dedication, and absorption (W. B. Schaufeli, M. Salanova, V. González-Roma, & A. B. Bakker, 2002)--has become a popular subject among academic and industry researchers. Following suggestions in the recent literature calling for further examination of the underlying factors comprising the construct of engagement, the authors investigated the factor structure of W. B. Schaufeli et al.'s measure of engagement and academic engagement's relation to academic satisfaction. Previous researchers found a 3-factor structure of engagement that comprises vigor, dedication, and absorption. The authors administered to a sample of university students a questionnaire on their level of engagement in academic work and various other measures. The results did not confirm the 3-factor structure. The present authors found engagement and satisfaction to be highly related constructs.}, } @article {pmid19151187, year = {2009}, author = {Huang, H and Shi, P and Wang, Y and Luo, H and Shao, N and Wang, G and Yang, P and Yao, B}, title = {Diversity of beta-propeller phytase genes in the intestinal contents of grass carp provides insight into the release of major phosphorus from phytate in nature.}, journal = {Applied and environmental microbiology}, volume = {75}, number = {6}, pages = {1508-1516}, pmid = {19151187}, issn = {1098-5336}, mesh = {6-Phytase/*genetics ; Amino Acid Sequence ; Animals ; Bacteria/*classification/*enzymology/genetics/isolation & purification ; Carps/*microbiology ; Cluster Analysis ; Gastrointestinal Contents/*microbiology ; Molecular Sequence Data ; Phosphorus/*metabolism ; Phylogeny ; Phytic Acid/*metabolism ; Sequence Alignment ; Sequence Analysis, DNA ; Sequence Homology ; }, abstract = {Phytate is the most abundant organic phosphorus compound in nature, and microbial mineralization of phytate by phytase is a key process for phosphorus recycling in the biosphere. In the present study, beta-propeller phytase (BPP) gene fragments were readily amplified from the intestinal contents of grass carp (Ctenopharyngodon idellus) directly or from phytate-degrading isolates from the same source, confirming the widespread occurrence of BPP in aquatic communities. The amounts of sequences collected using these two methods differed (88 distinct genes versus 10 isolates), but the sequences showed the same general topology based on phylogenetic analysis. All of the sequences fell in five clusters and were distinct from those of Anabaena, Gloeobacter, Streptomyces, Flavobacterium, Prosthecochloris, and Desulfuromonas, which have never been found in the grass carp intestine. Analysis of the microbial diversity by denaturing gradient gel electrophoresis demonstrated that unculturable bacteria were dominant bacteria in the grass carp intestine and thus the predominant phytate-degrading organisms. The predominant cultured species corresponding to the phytate-degrading isolates, Pseudomonas, Bacillus and Shewanella species, might be the main source of known BPPs. A phytase from Brevundimonas was first obtained from cultured species. Combining our results with Lim et al.'s inference that phytate-mineralizing bacteria are widely distributed and highly diverse in nature (B. L. Lim, P. Yeung, C. Cheng, and J. E. Hill, ISME J. 1:321-330, 2007), we concluded that BPP is the major phytate-degrading enzyme in nature, that most of this enzyme might originate from unculturable bacteria, and that the distribution of BPP may be related to the type of niche. To our knowledge, this is the first study to experimentally estimate BPP diversity in situ.}, } @article {pmid19150519, year = {2009}, author = {De Smedt, B and Reynvoet, B and Swillen, A and Verschaffel, L and Boets, B and Ghesquière, P}, title = {Basic number processing and difficulties in single-digit arithmetic: evidence from Velo-Cardio-Facial Syndrome.}, journal = {Cortex; a journal devoted to the study of the nervous system and behavior}, volume = {45}, number = {2}, pages = {177-188}, doi = {10.1016/j.cortex.2007.06.003}, pmid = {19150519}, issn = {0010-9452}, mesh = {*Aptitude ; Case-Control Studies ; Child ; DiGeorge Syndrome/physiopathology/*psychology ; Female ; Humans ; Male ; *Mathematics ; Neuropsychological Tests ; *Problem Solving ; Psychomotor Performance ; *Reading ; *Verbal Behavior ; }, abstract = {It has been suggested that mathematical disabilities (MD) emerge as a consequence of impairments in basic number processing skills. The aim of the present study was to investigate basic number processing skills in children with Velo-Cardio-Facial Syndrome (VCFS), a common genetic disorder with a high prevalence of MD, and to examine whether these basic low-level skills account for their performance in single-digit arithmetic. Twenty-five children with VCFS and 25 individually matched controls (age range: 6-12 years) participated. They all completed two basic number processing tasks (number reading, number comparison) and three single-digit arithmetic tasks comprising addition, subtraction and multiplication. In the latter tasks, strategy use was recorded next to accuracy and speed. Our data revealed that children with VCFS were significantly slower than controls on number comparison but not on number reading. Analysis of the single-digit arithmetic data revealed that children with VCFS performed more poorly than controls on large addition and subtraction problems. Both groups did not differ on multiplication and small additions and subtractions. At the strategy level, children with VCFS were significantly slower in executing backup strategies in addition and subtraction, but showed preserved retrieval of arithmetic facts. Taken together, children with VCFS show a consistent pattern of deficits at the level of number representations, arithmetic operations and strategy use, which suggests an impaired quantity subsystem in terms of Dehaene et al.'s model (2003). Most importantly, the correlational analyses showed that basic number processing skills directly accounted for single-digit arithmetic performance and strategy use in the children of the present study.}, } @article {pmid19146293, year = {2008}, author = {Rainville, S and Clarke, A}, title = {Distinct perceptual grouping pathways revealed by temporal carriers and envelopes.}, journal = {Journal of vision}, volume = {8}, number = {15}, pages = {9.1-15}, pmid = {19146293}, issn = {1534-7362}, support = {P20 GM103505/GM/NIGMS NIH HHS/United States ; P20 RR020151/RR/NCRR NIH HHS/United States ; P20 RR20151-02/RR/NCRR NIH HHS/United States ; }, mesh = {Contrast Sensitivity ; Female ; Humans ; Male ; Photic Stimulation ; Sensory Thresholds ; *Space Perception ; *Time Perception ; Young Adult ; }, abstract = {S. E. Guttman, L. A. Gilroy, and R. Blake (2005) investigated whether observers could perform temporal grouping in multi-element displays where each local element was stochastically modulated over time along one of several potential dimensions--or "messenger types"--such as contrast, position, orientation, or spatial scale. Guttman et al.'s data revealed that grouping discards messenger type and therefore support a single-pathway model that groups elements with similar temporal waveforms. In the current study, we carried out three experiments in which temporal-grouping information resided either in the carrier, the envelope, or the combined carrier and envelope of each messenger's timecourse. Results revealed that grouping is highly specific for messenger type if carrier envelopes lack grouping information but largely messenger nonspecific if carrier envelopes contain grouping information. These imply that temporal grouping is mediated by several messenger-specific carrier pathways as well as by a messenger-nonspecific envelope pathways. Findings also challenge simple temporal-filtering accounts of perceptual grouping (E. H. Adelson & H. Farid, 1999).}, } @article {pmid19145034, year = {2009}, author = {Olivers, CN and Spalek, TM and Kawahara, J and Di Lollo, V}, title = {The attentional blink: increasing target salience provides no evidence for resource depletion. A commentary on Dux, Asplund, and Marois (2008).}, journal = {Psychonomic bulletin & review}, volume = {16}, number = {1}, pages = {214-8; discussion 219-24}, pmid = {19145034}, issn = {1069-9384}, mesh = {Attention ; *Attentional Blink ; *Color Perception ; Discrimination, Psychological ; Humans ; Orientation ; *Pattern Recognition, Visual ; Psychophysics ; Reaction Time ; Serial Learning ; }, abstract = {The authors have argued elsewhere that the attentional blink (AB; i.e., reduced target detection shortly after presentation of an earlier target) arises from blocked or disrupted perceptual input in response to distractors presented between the targets. When targets replace the intervening distractors, so that three targets (T1, T2, and T3) are presented sequentially, performance on T2 and T3 improves. Dux, Asplund, and Marois (2008) argued that T3 performance improves at the expense of T1, and thus provides evidence for resource depletion. They showed that when T1 is made more salient (and presumably draws more resources), an AB for T3 appears to reemerge. These findings can be better explained, however, by (1) the relationship between T1 and T2 (not T1 and T3) and (2) differential salience for T3 in the long-lag condition of Dux et al.'s study. In conclusion, the Dux et al. study does not present a severe challenge to input control theories of the AB.}, } @article {pmid19140263, year = {2008}, author = {Schänzer, W and Geyer, H}, title = {Comments on Lundby et al.'s "testing for recombinant human erythropoietin in urine: problems associated with current anti-doping testing". Comment of laboratory B on the publication by Lundby et al.}, journal = {Journal of applied physiology (Bethesda, Md. : 1985)}, volume = {105}, number = {6}, pages = {1996; author reply 1997-8}, doi = {10.1152/japplphysiol.zdg-8310-comm.2008}, pmid = {19140263}, issn = {8750-7587}, mesh = {Doping in Sports/*methods ; Electrophoresis, Polyacrylamide Gel ; Erythropoietin/*urine ; Humans ; Isoelectric Focusing ; Laboratories/standards ; Recombinant Proteins ; Reproducibility of Results ; }, } @article {pmid19140262, year = {2008}, author = {Saugy, M and Robinson, N and Lamon, S}, title = {Comments on Lundby et al.'s "testing for recombinant human erythropoietin in urine: problems associated with current anti-doping testing".}, journal = {Journal of applied physiology (Bethesda, Md. : 1985)}, volume = {105}, number = {6}, pages = {1995-6; author reply 1997-8}, doi = {10.1152/japplphysiol.zdg-8310-comm.2008}, pmid = {19140262}, issn = {8750-7587}, mesh = {Doping in Sports/*methods ; Double-Blind Method ; Erythropoietin/administration & dosage/*urine ; Hematocrit ; Humans ; Laboratories ; Recombinant Proteins ; }, } @article {pmid19140261, year = {2008}, author = {Skibeli, V}, title = {Comments on Lundby et al.'s "testing for recombinant human erythropoietin in urine: problems associated with current anti-doping testing".}, journal = {Journal of applied physiology (Bethesda, Md. : 1985)}, volume = {105}, number = {6}, pages = {1995; author reply 1997-8}, doi = {10.1152/japplphysiol.zdg-8310-comm.2008}, pmid = {19140261}, issn = {8750-7587}, mesh = {Doping in Sports/*methods ; Erythropoietin/*urine ; Humans ; Laboratories/standards ; Quality Control ; Recombinant Proteins ; Specimen Handling ; }, } @article {pmid19140260, year = {2008}, author = {Mørkeberg, J and Belhage, B and Damsgaard, R}, title = {Comments on Lundby et al.'s "testing for recombinant human erythropoietin in urine: problems associated with current anti-doping testing". Expanding the analysis reporting will lead to more efficient testing.}, journal = {Journal of applied physiology (Bethesda, Md. : 1985)}, volume = {105}, number = {6}, pages = {1994-5; author reply 1997-8}, doi = {10.1152/japplphysiol.zdg-8310-comm.2008}, pmid = {19140260}, issn = {8750-7587}, mesh = {Doping in Sports/*methods ; Erythropoietin/*urine ; Humans ; Isoelectric Focusing ; Laboratories/standards ; Recombinant Proteins ; Reproducibility of Results ; }, } @article {pmid19140259, year = {2008}, author = {Schumacher, YO and Pottgiesser, T}, title = {Comments on Lundby et al.'s "testing for recombinant human erythropoietin in urine: problems associated with current anti-doping testing". New strategies in the fight against doping are necessary.}, journal = {Journal of applied physiology (Bethesda, Md. : 1985)}, volume = {105}, number = {6}, pages = {1994; author reply 1997-8}, doi = {10.1152/japplphysiol.zdg-8310-comm.2008}, pmid = {19140259}, issn = {8750-7587}, mesh = {Doping in Sports/*methods/*trends ; Erythropoietin/*blood/*urine ; Hematocrit ; Hemoglobins/metabolism ; Humans ; Laboratories ; Recombinant Proteins ; Reference Standards ; }, } @article {pmid19140258, year = {2008}, author = {Lasne, F}, title = {Comments on Lundby et al.'s "testing for recombinant human erythropoietin in urine: problems associated with current anti-doping testing".}, journal = {Journal of applied physiology (Bethesda, Md. : 1985)}, volume = {105}, number = {6}, pages = {1993-4; author reply 1997-8}, doi = {10.1152/japplphysiol.zdg-8310-comm.2008}, pmid = {19140258}, issn = {8750-7587}, mesh = {Doping in Sports/*methods ; Electrophoresis, Polyacrylamide Gel ; Erythropoietin/*urine ; France ; Humans ; Isoelectric Focusing ; Laboratories/standards ; Recombinant Proteins ; }, } @article {pmid19140257, year = {2008}, author = {Kayser, B}, title = {Comments on Lundby et al.'s "testing for recombinant human erythropoietin in urine: problems associated with current anti-doping testing". A negative test cannot exclude doping.}, journal = {Journal of applied physiology (Bethesda, Md. : 1985)}, volume = {105}, number = {6}, pages = {1993; author reply 1997-8}, doi = {10.1152/japplphysiol.zdg-8310-comm.2008}, pmid = {19140257}, issn = {8750-7587}, mesh = {Doping in Sports/*methods ; Erythropoietin/*urine ; False Negative Reactions ; False Positive Reactions ; Humans ; Recombinant Proteins ; }, } @article {pmid19140256, year = {2008}, author = {Valeri, CR and Ragno, G}, title = {Comments on Lundby et al.'s "testing for recombinant human erythropoietin in urine: problems associated with current anti-doping testing".}, journal = {Journal of applied physiology (Bethesda, Md. : 1985)}, volume = {105}, number = {6}, pages = {1993; author reply 1997-8}, doi = {10.1152/japplphysiol.zdg-8310-comm.2008}, pmid = {19140256}, issn = {8750-7587}, mesh = {Doping in Sports/*methods ; Electrophoresis, Polyacrylamide Gel ; Erythropoietin/*urine ; France ; Humans ; Isoelectric Focusing ; Laboratories/standards ; Recombinant Proteins ; }, } @article {pmid19140255, year = {2008}, author = {Salvagno, GL and Guidi, GC}, title = {Comments on Lundby et al.'s "testing for recombinant human erythropoietin in urine: problems associated with current anti-doping testing". Problems associated with current anti-doping testing: is quality assessment a reliable solution?.}, journal = {Journal of applied physiology (Bethesda, Md. : 1985)}, volume = {105}, number = {6}, pages = {1992-3; author reply 1997-8}, doi = {10.1152/japplphysiol.zdg-8310-comm.2008}, pmid = {19140255}, issn = {8750-7587}, mesh = {Animals ; CHO Cells ; Cricetinae ; Cricetulus ; Doping in Sports/*methods ; Erythropoietin/*analysis/*urine ; Humans ; Isoelectric Focusing ; Male ; Recombinant Proteins ; }, } @article {pmid19140254, year = {2008}, author = {Jelkmann, WE}, title = {Comments on Lundby et al.'s "testing for recombinant human erythropoietin in urine: problems associated with current anti-doping testing". Testing for recombinant human erythropoietin--the bouquet of compounds.}, journal = {Journal of applied physiology (Bethesda, Md. : 1985)}, volume = {105}, number = {6}, pages = {1992; author reply 1997-8}, doi = {10.1152/japplphysiol.zdg-8310-comm.2008}, pmid = {19140254}, issn = {8750-7587}, mesh = {Doping in Sports/*methods ; Erythropoietin/*urine ; Humans ; Recombinant Proteins ; }, } @article {pmid19129785, year = {2009}, author = {Nordli, DR}, title = {The ketogenic diet, four score and seven years later.}, journal = {Nature clinical practice. Neurology}, volume = {5}, number = {1}, pages = {12-13}, pmid = {19129785}, issn = {1745-8358}, abstract = {This Practice Point commentary discusses the findings of Neal et al.'s randomized controlled trial of the ketogenic diet in children with refractory epilepsies. The authors showed that the ketogenic diet was superior to continuation of medical treatment in reducing seizure frequency in this patient population. On the basis of these and other results I argue three points, the first being supported by the literature and the others being personal opinion. First, the ketogenic diet should be considered for the treatment of children with drug-resistant epilepsy and not only as a last resort. Second, the allocation of resources to support professionals in administering the ketogenic diet is justifiable. Third, we must develop alternative strategies to randomized controlled trials if we wish to obtain timely information on effective treatment strategies for specific pediatric epilepsy syndromes.}, } @article {pmid19128811, year = {2009}, author = {Chapman, PM}, title = {Letter to the editor: Borja et al.'s (2008) "Overview of integrative tools and methods ... worldwide" omits key elements.}, journal = {Marine pollution bulletin}, volume = {58}, number = {3}, pages = {456; author reply 457-8}, doi = {10.1016/j.marpolbul.2008.12.002}, pmid = {19128811}, issn = {0025-326X}, mesh = {Conservation of Natural Resources/*methods ; Ecology/*methods ; Ecosystem ; Environmental Monitoring/*methods ; Environmental Pollution/analysis ; Oceans and Seas ; }, } @article {pmid19120580, year = {2009}, author = {Price, SL}, title = {Becoming a nurse: a meta-study of early professional socialization and career choice in nursing.}, journal = {Journal of advanced nursing}, volume = {65}, number = {1}, pages = {11-19}, doi = {10.1111/j.1365-2648.2008.04839.x}, pmid = {19120580}, issn = {1365-2648}, mesh = {*Attitude of Health Personnel ; *Career Choice ; *Career Mobility ; Education, Nursing/*standards ; Humans ; Job Satisfaction ; *Motivation ; *Nursing ; Personnel Turnover ; Socialization ; }, abstract = {AIM: This paper is a report of a meta-study of early professional socialization and career choice in nursing.

BACKGROUND: The current and growing shortage of nurses is a global issue, and nursing recruitment and retention are recognized priorities internationally. The future of nursing will lie in the ability to recruit and retain the next generation to the profession.

DATA SOURCES: Studies were identified through a search of the CINAHL, PsycInfo, Sociological Abstracts, PubMed; Medline and Embase databases from 1990 to 2007.

REVIEW METHODS: Studies were included if they gave insight into the experience of choosing nursing as a career, used qualitative methodology and methods, and were published in English. Analysis was undertaken using Paterson et al.'s framework for qualitative meta-synthesis.

RESULTS: Ten primary studies were included in the review. Their methodologies included: ethnography (4); descriptive qualitative (3); grounded theory (2); and phenomenology (1). The location of the research was Canada (3), United Kingdom (2), United States of America (2), Australia (1), Japan (1) and Sweden (1). Three main themes were identified: influence of ideals; paradox of caring and role of others.

CONCLUSION: Career choice and early professional socialization are influenced by multiple factors. In future recruitment and retention strategies to address the critical nursing shortage, it is important to consider the role of mentors, peers and role models in the formulation of career expectations, and career choice decisions. It is also necessary to consider the role of mentors, peers and role models in the formulation of career expectations, and career choice decisions.}, } @article {pmid21243091, year = {2009}, author = {Jason, LA and Porter, N and Brown, M and Anderson, V and Brown, A and Hunnell, J and Lerch, A}, title = {CFS: A Review of Epidemiology and Natural History Studies.}, journal = {Bulletin of the IACFS/ME}, volume = {17}, number = {3}, pages = {88-106}, pmid = {21243091}, support = {R01 AI055735/AI/NIAID NIH HHS/United States ; }, abstract = {Almost all studies with samples of patients who have chronic fatigue syndrome (CFS) have relied on referrals from physicians or health facilities. Under-served minorities, who not only tend to manifest higher levels of chronic illness, but are also less likely to seek and receive adequate medical care, have not been represented in these studies (1). This may have contributed to an under-estimation of CFS among minority groups (2). Few studies have derived their samples from socioeconomically and ethnically diverse community-based populations. A technical report issued by the Agency for Healthcare Research and Quality (3) concluded that estimating rates of recovery/improvement or relapse from CFS are not possible because there are so few natural history studies and those that are available have involved selected referral populations. This paper provides a review of epidemiologic studies of CFS followed by a discussion of diagnostic issues and risk factors for the illness. Findings from Jason et al.'s (4) epidemiologic study in a multi-ethnic, economically diverse urban area are highlighted as this research group is now examining the natural course of CFS over the past 10 years with this community-based sample. The current study will add to current epidemiologic and risk factors research by assessing the course, progression, and risk factors of CFS among a demographically diverse sample of participants who are unbiased by illness, help-seeking behaviors, or differential access to the health care system.}, } @article {pmid20425983, year = {2009}, author = {Martín-Fernández, MA and Martín-Fernández, M and Alberola-López, C}, title = {A Log-Euclidean polyaffine registration for articulated structures in medical images.}, journal = {Medical image computing and computer-assisted intervention : MICCAI ... International Conference on Medical Image Computing and Computer-Assisted Intervention}, volume = {12}, number = {Pt 1}, pages = {156-164}, doi = {10.1007/978-3-642-04268-3_20}, pmid = {20425983}, mesh = {*Algorithms ; Arthrography/*methods ; *Artificial Intelligence ; Finger Joint/*diagnostic imaging ; Humans ; Pattern Recognition, Automated/*methods ; Radiographic Image Enhancement/*methods ; Radiographic Image Interpretation, Computer-Assisted/*methods ; Reproducibility of Results ; Sensitivity and Specificity ; *Subtraction Technique ; }, abstract = {In this paper we generalize the Log-Euclidean polyaffine registration framework of Arsigny et al. to deal with articulated structures. This framework has very useful properties as it guarantees the invertibility of smooth geometric transformations. In articulated registration a skeleton model is defined for rigid structures such as bones. The final transformation is affine for the bones and elastic for other tissues in the image. We extend the Arsigny el al.'s method to deal with locally-affine registration of pairs of wires. This enables the possibility of using this registration framework to deal with articulated structures. In this context, the design of the weighting functions, which merge the affine transformations defined for each pair of wires, has a great impact not only on the final result of the registration algorithm, but also on the invertibility of the global elastic transformation. Several experiments, using both synthetic images and hand radiographs, are also presented.}, } @article {pmid19110236, year = {2009}, author = {Pössel, P}, title = {Cognitive Triad Inventory (CTI): psychometric properties and factor structure of the German translation.}, journal = {Journal of behavior therapy and experimental psychiatry}, volume = {40}, number = {2}, pages = {240-247}, doi = {10.1016/j.jbtep.2008.12.001}, pmid = {19110236}, issn = {1873-7943}, mesh = {Adolescent ; Adult ; Cognition/*physiology ; Depression/epidemiology/psychology ; Factor Analysis, Statistical ; Female ; Germany ; Humans ; Language ; Male ; Middle Aged ; Neuropsychological Tests ; *Psychometrics ; Psychomotor Performance/physiology ; Reproducibility of Results ; Self Concept ; Young Adult ; }, abstract = {A central component of Beck, A. T., Rush, J., & Shaw, B. F. [(1979). Cognitive therapy of depression. New York: Guilford Press] cognitive theory of depression is the cognitive triad (negative view of self, world, and future) measurable with the Cognitive Triad Inventory (CTI). This study examined the psychometric properties and factor structure of the German CTI in a sample of 796 German volunteers. The study provides evidence for the reliability and validity of the German CTI and of independent positive and negative elements of the cognitive triad. Furthermore, results emphasize methodological above conceptual problems in Beck et al.'s (1979) theory as cause for instabilities in the CTI's factor structure across different studies.}, } @article {pmid19109831, year = {2009}, author = {Russell, RT and Feurer, ID and Wisawatapnimit, P and Pinson, CW}, title = {The validity of EQ-5D US preference weights in liver transplant candidates and recipients.}, journal = {Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society}, volume = {15}, number = {1}, pages = {88-95}, doi = {10.1002/lt.21648}, pmid = {19109831}, issn = {1527-6473}, support = {1 F32DK077482-02)/DK/NIDDK NIH HHS/United States ; }, mesh = {Adult ; Aged ; Cohort Studies ; Female ; Humans ; Liver Diseases/*therapy ; Liver Transplantation/*methods ; Male ; Middle Aged ; Psychometrics/instrumentation/*methods ; *Quality of Life ; Reproducibility of Results ; Surveys and Questionnaires ; Treatment Outcome ; United States ; }, abstract = {Health utility instruments assess patients' valuation of specific health states, which can be converted to quality-adjusted life years for cost-utility analysis. Data from the EQ-5D, a generic health-related quality of life questionnaire from EuroQoL, can be reported as 5 health status scores or as a single health preference weight (HPW). US population-based HPWs were published by Shaw and colleagues in 2005 (Med Care 2005;43:203-220). Our aim was to test the validity of US EQ-5D HPWs and health status scores in liver transplant patients. EQ-5D scores were converted to HPWs with Shaw et al.'s model. Data were stratified by measurement period: pretransplant period, early posttransplant period (< or =12 months), intermediate posttransplant period (13-36 months), and late posttransplant period (>36 months). EQ-5D scores were compared to specific, hypothesized Short Form 36 Health Survey, Center for Epidemiologic Studies Depression Scale, and Beck Anxiety Inventory scores that were identified a priori on the basis of construct similarity. Criterion-related and construct validity were tested with nonparametric methods. Two hundred eighty-five adults participated (113 in the pretransplant period, 60 in the early posttransplant period, 47 in the intermediate posttransplant period, and 65 in the late posttransplant period), and follow-up averaged 36 +/- 36 months. Eighty-one percent of the hypothesized relationships between EQ-5D and gold-standard scales were strong (r > or = |0.5|, P < 0.001), and the remainder were moderate (r > |0.3|, P < 0.001). Differences between pretransplant and posttransplant EQ-5D HPWs were statistically significant. In conclusion, EQ-5D dimensions and the health utility index generated from Shaw's US population preference weights demonstrated criterion-related and construct validity in liver transplant patients. It is a valid instrument for cost-utility analysis in this setting.}, } @article {pmid19099585, year = {2008}, author = {Edwards, N and Semenic, S and Premji, S and Montgomery, P and Williams, B and Olson, J and Mansi, O}, title = {Provincial prenatal record revision: a multiple case study of evidence-based decision-making at the population-policy level.}, journal = {BMC health services research}, volume = {8}, number = {}, pages = {266}, pmid = {19099585}, issn = {1472-6963}, mesh = {Alcohol Drinking/adverse effects ; Canada ; Decision Making ; *Evidence-Based Emergency Medicine ; Female ; Humans ; *Medical Records ; Pregnancy ; Prenatal Care/methods/*standards ; *Professional Practice ; Smoking Cessation ; }, abstract = {BACKGROUND: There is a significant gap in the knowledge translation literature related to how research evidence actually contributes to health care decision-making. Decisions around what care to provide at the population (rather than individual) level are particularly complex, involving considerations such as feasibility, cost, and population needs in addition to scientific evidence. One example of decision-making at this "population-policy" level involves what screening questions and intervention guides to include on standardized provincial prenatal records. As mandatory medical reporting forms, prenatal records are potentially powerful vehicles for promoting population-wide evidence-based care. However, the extent to which Canadian prenatal records reflect best-practice recommendations for the assessment of well-known risk factors such as maternal smoking and alcohol consumption varies markedly across Canadian provinces and territories. The goal of this study is to better understand the interaction of contextual factors and research evidence on decision-making at the population-policy level, by examining the processes by which provincial prenatal records are reviewed and revised.

METHODS: Guided by Dobrow et al.'s (2004) conceptual model for context-based evidence-based decision-making, this study will use a multiple case study design with embedded units of analysis to examine contextual factors influencing the prenatal record revision process in different Canadian provinces and territories. Data will be collected using multiple methods to construct detailed case descriptions for each province/territory. Using qualitative data analysis techniques, decision-making processes involving prenatal record content specifically related to maternal smoking and alcohol use will be compared both within and across each case, to identify key contextual factors influencing the uptake and application of research evidence by prenatal record review committees. All study participants will be required to give written informed consent prior to participating in data collection.

CONCLUSION: This study will advance knowledge in the field of evidence-based decision-making by illustrating the complex interaction of contextual factors and evidence on health policy decision-making by provincial-level committees. By increasing the transparency of decision-making within provincial prenatal record committees, this study will help inform more effective strategies for enhancing the integration of best-practice evidence into prenatal records.}, } @article {pmid19088820, year = {2008}, author = {Acutis, PL and Peletto, S and Grego, E and Colussi, S and Riina, MV and Rosati, S and Mignone, W and Caramelli, M}, title = {Comment on "Comparative genomic analysis of the whale (Pseudorca crassidens) PRNP locus".}, journal = {Genome}, volume = {51}, number = {12}, pages = {1062}, doi = {10.1139/G08-091}, pmid = {19088820}, issn = {0831-2796}, mesh = {Animals ; Comparative Genomic Hybridization/*methods ; Genetic Predisposition to Disease ; Prion Diseases/genetics ; Prions/*genetics ; Quantitative Trait Loci/genetics ; Whales/*genetics ; }, abstract = {A reminder that another paper on the cetacean PRNP locus has been published before Kim et al.'s paper (2008. Genome, 51: 452-464) is presented along with a consideration of the related results.}, } @article {pmid19068337, year = {2008}, author = {Mechri, A and Slama, H and Bourdel, MC and Chebel, S and Mandhouj, O and Krebs, MO and Gaha, L}, title = {[Neurological soft signs in schizophrenic patients and their nonaffected siblings].}, journal = {L'Encephale}, volume = {34}, number = {5}, pages = {483-489}, doi = {10.1016/j.encep.2007.08.009}, pmid = {19068337}, issn = {0013-7006}, mesh = {Adolescent ; Adult ; Female ; Genetic Predisposition to Disease/genetics/psychology ; Humans ; Male ; Middle Aged ; Nervous System Diseases/diagnosis/*genetics ; *Neurologic Examination ; Phenotype ; Psychiatric Status Rating Scales ; Risk Factors ; Schizophrenia/diagnosis/*genetics ; Schizotypal Personality Disorder/genetics/psychology ; }, abstract = {BACKGROUND: Neurological soft signs (NSS) are subtle neurological signs indicating non specific cerebral dysfunction. Several studies have found an excess of NSS in schizophrenic patients compared to healthy subjects. Although NSS have been consistently reported in schizophrenic patients, their clinical relevance and their relation to functional impairment and severity of this disease are not well-clarified. In addition, the presence of NSS in schizophrenic patient's relatives suggests that they could be associated with the genetic liability.

OBJECTIVES: To determine the prevalence and scores of NSS in schizophrenic patients and their nonaffected siblings and to examine the clinical correlates of NSS in the schizophrenic patients.

METHOD: Sixty-six schizophrenic patients (50 males and 16 females, mean age=31.16+/-7.17 years), were compared to 31 of their nonaffected siblings (22 males and nine females, mean age=32.19+/-5.88 years) and to 60 controls subjects (40 males and 20 females, mean age=30.70+/-6.54 years) without family psychiatric history. NSS were assessed with Krebs et al.'s neurological soft signs scale. It is a comprehensive and standardized scale consisting of 23 items comporting five factors: motor coordination, motor integration, sensory integration, quality of lateralization and involuntary movements or posture. The Simpson and Angus scale for extrapyramidal symptoms was also rated. Clinical assessment of the schizophrenic patients was conducted using the positive and negative syndrome scale (PANSS), clinical global impressions (CGI) and global functioning evaluation (GAF). Psychiatric disorders were ruled out among siblings of schizophrenic patients and control subjects by psychiatric review evaluation, according to the DSM-IV check list.

RESULTS: When the total NSS score of 11.5 was considered the cut-off point, the prevalence of NSS was 96.9% in the schizophrenic patients versus 35.5% in the nonaffected siblings (p<0.0001). Schizophrenic patients had also significantly higher NSS total score and subscores than the siblings and control groups. The NSS total score was 19.51+/-5.28 in the schizophrenic patients, 10.77+/-3.38 in their nonaffected siblings and 4.23+/-2.07 in control subjects (p<0.0001). The NSS total score and subscores in the siblings group were intermediate between those of the schizophrenic patients and those of the control subjects. The motor coordination, motor integration and sensory integration subscores were higher in schizophrenic patients and their nonaffected siblings. The NSS total score correlated positively with the negative (p<0.0001) and disorganization symptoms (p=0.001) subscores and total score of PANSS (p=0.004). The PANSS total score and negative and disorganization subscores also correlated positively with the motor integration and quality of laterality subscores of NSS. The NSS total score was significantly correlated with severity of illness (p<0.0001), lower educational level (p=0.002) and poor global functioning (p=0.003).

CONCLUSIONS: The association between NSS with negative and disorganization dimensions of schizophrenia supports that neurological dysfunction is an intrinsic characteristic of the illness and may distinguish a subgroup of patients with poor illness course and outcome. The NSS could be a trait marker useful in phenotypic characterization of schizophrenic patients and identification of vulnerability in genetically high-risk subjects.}, } @article {pmid19065131, year = {2009}, author = {Ito, J and Fukagawa, M}, title = {Predicting the risk of acute kidney injury in earthquake victims.}, journal = {Nature clinical practice. Nephrology}, volume = {5}, number = {2}, pages = {64-65}, pmid = {19065131}, issn = {1745-8331}, abstract = {Acute kidney injury (AKI), mainly as a result of crush syndrome, is the second most common cause of death in large earthquakes. It is well known that AKI is preventable with early management (particularly with fluid therapy), but a means of determining which patients are at risk is needed. This Practice Point commentary discusses Najafi et al.'s analysis of data from an earthquake in Iran in December 2003, from which they propose two decision rules that use routine data to predict development of AKI. The first rule uses serum levels of creatinine, lactate dehydrogenase and uric acid on day 1 to predict the risk of AKI. The second rule predicts serum creatinine level on day 3 using serum creatine phosphokinase, lactate dehydrogenase, potassium and uric acid level. Although further investigation in a larger number of patients and in different disaster situations is needed to confirm the validity of these simple rules, they might be very useful, particularly for non-nephrologists and rescue staff, for the early identification of disaster victims at high risk of AKI.}, } @article {pmid19065129, year = {2009}, author = {Tarng, DC}, title = {The conundrum of serum ferritin measurement in patients with chronic kidney disease.}, journal = {Nature clinical practice. Nephrology}, volume = {5}, number = {2}, pages = {66-67}, pmid = {19065129}, issn = {1745-8331}, abstract = {Serum ferritin level, the most commonly used marker for determining iron status in patients with chronic kidney disease, is influenced by factors such as inflammation and malnutrition. Moreover, there seems to be considerable biological variability and analytical variation between different serum ferritin assays. This Practice Point commentary discusses a recent paper by Ford et al. that examined the interassay differences and short-term intraindividual variability of serum ferritin measurements in patients on chronic hemodialysis. A comparison of six commonly used serum ferritin immunoassays revealed intermethod variation of up to 337 pmol/l among hemodialysis and nonhemodialysis patients. The intraindividual coefficients of variation for serum ferritin level in 60 stable hemodialysis patients ranged from 2% to 62% over an initial 2-week period and from 3% to 52% over a 6-week period. This commentary discusses Ford et al.'s paper and supports the conclusion that nephrologists should not use a single serum ferritin value to guide intravenous iron treatment in patients on chronic hemodialysis.}, } @article {pmid19061503, year = {2008}, author = {Nix, DA and Courdy, SJ and Boucher, KM}, title = {Empirical methods for controlling false positives and estimating confidence in ChIP-Seq peaks.}, journal = {BMC bioinformatics}, volume = {9}, number = {}, pages = {523}, pmid = {19061503}, issn = {1471-2105}, support = {P01CA24014/CA/NCI NIH HHS/United States ; }, mesh = {Algorithms ; Animals ; Cell Transformation, Neoplastic ; Chromatin/chemistry ; Chromatin Immunoprecipitation/*methods ; False Positive Reactions ; Gene Expression Regulation ; Genome ; Histones/chemistry ; Humans ; Neurons/metabolism ; Poisson Distribution ; Polymerase Chain Reaction ; Proteins/chemistry ; Sequence Analysis, DNA ; }, abstract = {BACKGROUND: High throughput signature sequencing holds many promises, one of which is the ready identification of in vivo transcription factor binding sites, histone modifications, changes in chromatin structure and patterns of DNA methylation across entire genomes. In these experiments, chromatin immunoprecipitation is used to enrich for particular DNA sequences of interest and signature sequencing is used to map the regions to the genome (ChIP-Seq). Elucidation of these sites of DNA-protein binding/modification are proving instrumental in reconstructing networks of gene regulation and chromatin remodelling that direct development, response to cellular perturbation, and neoplastic transformation.

RESULTS: Here we present a package of algorithms and software that makes use of control input data to reduce false positives and estimate confidence in ChIP-Seq peaks. Several different methods were compared using two simulated spike-in datasets. Use of control input data and a normalized difference score were found to more than double the recovery of ChIP-Seq peaks at a 5% false discovery rate (FDR). Moreover, both a binomial p-value/q-value and an empirical FDR were found to predict the true FDR within 2-3 fold and are more reliable estimators of confidence than a global Poisson p-value. These methods were then used to reanalyze Johnson et al.'s neuron-restrictive silencer factor (NRSF) ChIP-Seq data without relying on extensive qPCR validated NRSF sites and the presence of NRSF binding motifs for setting thresholds.

CONCLUSION: The methods developed and tested here show considerable promise for reducing false positives and estimating confidence in ChIP-Seq data without any prior knowledge of the chIP target. They are part of a larger open source package freely available from http://useq.sourceforge.net/.}, } @article {pmid19057522, year = {2009}, author = {Muñoz-Cachón, MJ and Salces, I and Arroyo, M and Ansotegui, L and Rocandio, AM and Rebato, E}, title = {Overweight and obesity: prediction by silhouettes in young adults.}, journal = {Obesity (Silver Spring, Md.)}, volume = {17}, number = {3}, pages = {545-549}, doi = {10.1038/oby.2008.541}, pmid = {19057522}, issn = {1930-7381}, mesh = {Adolescent ; Adult ; Anthropology, Physical ; Anthropometry ; *Art ; Body Height ; *Body Size ; Body Weight ; Cross-Sectional Studies ; Female ; Humans ; Male ; Obesity/diagnosis/*epidemiology ; Overweight/diagnosis/*epidemiology ; Predictive Value of Tests ; Prevalence ; ROC Curve ; Sensitivity and Specificity ; Spain ; Young Adult ; }, abstract = {The present study analyzes the prevalence of overweight/obesity in a sample of young adults from the University of the Basque Country (Spain), and tests the efficiency of the silhouettes to predict overweight/obesity. This cross-sectional study was conducted in a sample of volunteer university students from the University of the Basque Country (356 men and 745 women, age: 18-33 years), who came to the Physical Anthropology laboratory where a standardized questionnaire was administered and anthropometric measurements were taken by a well-trained anthropometrist. Height and weight were obtained. BMI was calculated as weight/height(2) (kg/m(2)) and it was used as a reference method. Using a questionnaire, based on the standard figural stimuli, subjects were asked to choose the silhouette which was closest to his/her usual appearance (current body size). The accuracy of the Williamson et al.'s silhouettes as an overweight-obesity indicator was analyzed by gender-specific receiver operating curve (ROC). The cutoff figure to distinguish between nonoverweight and overweight-obese individuals corresponded to number 7 in men and 6 in women. These cutoff values matched optimal sensitivity and specificity, with few nonoverweight subjects selecting silhouettes bigger than 7 in the case of men or 6 for women. In conclusion, the figural stimuli allows the identification of populations at overweight/obesity risk with the simple use of silhouettes, at least in this rank of age, where the overweight and obesity are yet little frequent.}, } @article {pmid19051931, year = {2008}, author = {Cho, DG and Na, JG and Choi, JB and Kim, YJ and Kim, T}, title = {Effect of slip boundary condition on the design of nanoparticle focusing lenses.}, journal = {Journal of nanoscience and nanotechnology}, volume = {8}, number = {7}, pages = {3741-3748}, doi = {10.1166/jnn.2008.002}, pmid = {19051931}, issn = {1533-4880}, abstract = {The importance of nanoparticles as a building block for novel application has been emphasized in various fields. Especially, nanoparticle beam has been widely used to measure particle size distribution, synthesize materials, and generate micro-patterns, as it can enhance the measurement resolution and transport efficiency. The aerodynamic lens system has been developed to focus particles in a certain size range. The manufacturing of nanoparticles in gas phase is typically performed at the low pressure conditions and the design and simulation of lens at low pressure have been steadily reported. The computational fluid dynamics (CFD) has been utilized to analyze the flow field and obtain particle trajectories. However, previous work has used no-slip boundary condition at low pressure. This paper describes the lens design and simulation with slip boundary condition at low pressure (approximately 1 Torr). The design of lens is discussed on the basis of the Wang et al.'s guidelines and the commercial code FLUENT is used for simulation. The results of this study show that the difference of particle beam radius between no-slip and slip boundary conditions is 0.03 approximately 0.9 mm for particle size ranging from 3 to 200 nm with Brownian diffusion and that the transport efficiency is slightly higher with slip boundary condition.}, } @article {pmid19050345, year = {2008}, author = {Lippi, G}, title = {Comments on Lundby et al.'s "testing for recombinant human erythropoietin in urine: problems associated with current anti-doping testing". Anti-doping testing: friend or foe?.}, journal = {Journal of applied physiology (Bethesda, Md. : 1985)}, volume = {105}, number = {6}, pages = {1992; author reply 1997-8}, doi = {10.1152/japplphysiol.zdg-8310-comm.2008}, pmid = {19050345}, issn = {8750-7587}, mesh = {Doping in Sports/*methods ; Erythropoietin/*urine ; Humans ; Recombinant Proteins ; }, } @article {pmid19027184, year = {2009}, author = {Grant, D}, title = {Physician financial incentives and cesarean delivery: new conclusions from the healthcare cost and utilization project.}, journal = {Journal of health economics}, volume = {28}, number = {1}, pages = {244-250}, doi = {10.1016/j.jhealeco.2008.09.005}, pmid = {19027184}, issn = {0167-6296}, mesh = {Adult ; Cesarean Section/*statistics & numerical data ; Female ; Humans ; Middle Aged ; Physician Incentive Plans/*economics ; Pregnancy ; United States ; Young Adult ; }, abstract = {This paper replicates Gruber et al.'s [Gruber, J., Kim, J., Mayzlin, D., 1999. Physician fees and procedure intensity: the case of cesarean delivery. Journal of Health Economics, 18 (4), 473-490] analysis of the effect of physician financial incentives on cesarean delivery rates, using their data, sample selection criteria, and specification. Coincident trends explain much of their estimated positive relation between fees and cesarean utilization, which also falls somewhat upon the inclusion of several childbirth observations that had been inadvertently excluded from their estimation sample. The data ultimately indicate that a $1000 increase, in current dollars, in the reimbursement for a cesarean section increases cesarean delivery rates by about one percentage point, one-quarter of the effect estimated originally.}, } @article {pmid19026108, year = {2009}, author = {Ling, J and Burton, TC and Salt, JL and Muncer, SJ}, title = {Psychometric analysis of the systemizing quotient (SQ) scale.}, journal = {British journal of psychology (London, England : 1953)}, volume = {100}, number = {Pt 3}, pages = {539-552}, doi = {10.1348/000712608X368261}, pmid = {19026108}, issn = {0007-1269}, mesh = {Chi-Square Distribution ; Empathy ; Factor Analysis, Statistical ; Female ; Humans ; Individuality ; Intelligence ; Male ; Models, Statistical ; Personality Assessment/*statistics & numerical data ; Psychometrics ; Sex Distribution ; Sex Factors ; Space Perception ; Surveys and Questionnaires ; }, abstract = {The psychometric properties of the systemizing quotient (SQ) developed by Baron-Cohen (2003) are investigated in three studies. Furthermore, we examine the notion that the ability to systemize should be independent of intelligence. In Studies 1 and 2, confirmatory factor analyses are used to examine the factor structure of the SQ. Study 3 examines the relationship between systemizing, mental rotation and intelligence. Studies 1 and 2 indicate that the SQ does not possess a unifactorial structure but is best considered as four related factors; Study 3 found that SQ was not related to intelligence, although mental rotation was. A four factor structure using fewer items was a better fit for the data than either the original version of the SQ or Wakabayashi et al.'s (2006) revised version. Overall these results support Baron-Cohen's view that SQ is not related to intelligence. Although mental rotation is correlated to SQ, it is not the main determinant of SQ. The problems of self-report measures are discussed along with the difficulties related to measuring systemizing.}, } @article {pmid19025899, year = {2009}, author = {Mahmood, I}, title = {Role of fixed coefficients and exponents in the prediction of human drug clearance: how accurate are the predictions from one or two species?.}, journal = {Journal of pharmaceutical sciences}, volume = {98}, number = {7}, pages = {2472-2493}, doi = {10.1002/jps.21597}, pmid = {19025899}, issn = {1520-6017}, mesh = {Animals ; Biological Availability ; *Biometry ; Dogs ; Haplorhini ; Humans ; Metabolic Clearance Rate ; Mice ; Models, Biological ; *Pharmacokinetics ; Rats ; }, abstract = {Pharmacokinetic (PK) interspecies scaling is generally conducted using PK data from at least three animal species but three animal species may not be always available. In a recent manuscript, Tang et al. have described the methods to predict human drug clearance using one or two animal species. The authors claim that their proposed methods are better than the rule of exponents (ROE) which uses at least three animal species for the prediction of human drug clearance. A thorough examination of Tang et al.'s manuscript indicates that the data analysis may not be accurate. Considering that Tang et al.'s method may be of value, the objective of this study was to extend Tang et al.'s proposed methods for drugs given both intravenously and orally. The results of this study indicate that human drug clearance cannot be predicted with reasonable accuracy for most of the drugs by Tang et al.'s proposed methods and the accuracy of the prediction obtained from the ROE remains more accurate (based on average fold-error) than the one or two-species methods. This manuscript also clarifies some incorrect views regarding ROE presented by Tang et al. in their manuscript.}, } @article {pmid19020885, year = {2009}, author = {Hong, SK and Han, BK and Lee, ST and Kim, SS and Min, KE and Jeong, SJ and Jeong, H and Byun, SS and Lee, HJ and Choe, G and Lee, SE}, title = {Prediction of Gleason score upgrading in low-risk prostate cancers diagnosed via multi (> or = 12)-core prostate biopsy.}, journal = {World journal of urology}, volume = {27}, number = {2}, pages = {271-276}, pmid = {19020885}, issn = {1433-8726}, mesh = {Adult ; Aged ; Biopsy/methods/statistics & numerical data ; Humans ; Male ; Middle Aged ; Predictive Value of Tests ; Prostate/*pathology ; Prostatectomy ; Prostatic Neoplasms/*pathology/surgery ; Risk Factors ; }, abstract = {OBJECTIVES: A paucity of data exists on actual pathology of the contemporary patients strictly categorized as having low-risk prostate cancer. We tried to identify useful preoperative predictors of Gleason score upgrading in patients who underwent radical retropubic prostatectomy (RRP) for low-risk prostate cancer diagnosed via multi-core prostate biopsy.

METHODS: A total of 203 patients who underwent radical RRP for low-risk prostate cancer, as defined by D'Amico et al.'s classification (clinical stage < or = T2a, biopsy Gleason sum < or = 6, and PSA < or = 10 ng/ml), detected via multi (> or = 12)-core prostate biopsy were enrolled. We reviewed patients preoperative and pathological data.

RESULTS: Among all subjects, 81 (39.9%) were upgraded to Gleason score > or = 7 after RRP, whereas no downgrading was observed. In multivariate analysis, only preoperative PSA level (P = 0.024) and number of positive cores (P = 0.027) were observed to be independent predictors of Gleason score upgrading following RRP. Also, Gleason core upgrading was observed to be significantly associated with extraprostatic extension of tumor (P < 0.001) and positive surgical margin (P = 0.002).

CONCLUSIONS: A significant proportion of patients with low-risk prostate cancer as defined by D'Amico et al.'s classification diagnosed via multi-core prostate biopsy in contemporary period may have Gleason score upgrading following RRP. For patients with low-risk prostate cancer, preoperative PSA level and number of positive cores may be useful predictors of Gleason score upgrading, which was observed to significantly associated with other adverse pathologic features.}, } @article {pmid19014266, year = {2008}, author = {Thomas, E and Murphy, M and Pitt, R and Rivers, A and Leavens, DA}, title = {Understanding of visual attention by adult humans (Homo sapiens): a partial replication of Povinelli, Bierschwale, and Cech (1999).}, journal = {Journal of comparative psychology (Washington, D.C. : 1983)}, volume = {122}, number = {4}, pages = {428-436}, doi = {10.1037/0735-7036.122.4.428}, pmid = {19014266}, issn = {0735-7036}, mesh = {Adult ; Age Factors ; Animals ; *Attention ; Female ; Fixation, Ocular ; Humans ; Male ; Motivation ; *Orientation ; Pan troglodytes/psychology ; *Personal Construct Theory ; Practice, Psychological ; Species Specificity ; *Visual Perception ; Young Adult ; }, abstract = {Povinelli, Bierschwale, and Cech (1999) reported that when tested on a visual attention task, the behavior of juvenile chimpanzees did not support a high-level understanding of visual attention. This study replicates their research using adult humans and aims to investigate the validity of their experimental design. Participants were trained to respond to pointing cues given by an experimenter, and then tested on their ability to locate hidden objects from visual cues. Povinelli et al.'s assertion that the generalization of pointing to gaze is indicative of a high-level framework was not supported by our findings: Training improved performance only on initial probe trials when the experimenter's gaze was not directed at the baited cup. Furthermore, participants performed above chance on such trials, the same result exhibited by chimpanzees and used as evidence by Povinelli et al. to support a low-level framework. These findings, together with the high performance of participants in an incongruent condition, in which the experimenter pointed to or gazed at an unbaited container, challenge the validity of their experimental design.}, } @article {pmid19002135, year = {2009}, author = {Spiegel, DM}, title = {Interpreting observational studies of disordered mineral metabolism and mortality in patients on hemodialysis.}, journal = {Nature clinical practice. Nephrology}, volume = {5}, number = {1}, pages = {16-17}, pmid = {19002135}, issn = {1745-8331}, abstract = {This Practice Point commentary discusses the findings and limitations of a cohort study reported by Wald and colleagues of mineral metabolism in patients on hemodialysis. The investigators' observational analysis utilized data from the 1,846 patients in the randomized, controlled Hemodialysis (HEMO) Study. Wald et al.'s advantages include the well-characterized dataset, particularly with regard to comorbid conditions. However, the authors found it impossible to analyze the potentially confounding effect of concomitant medications. Furthermore, the relatively small dataset, especially compared with those of previous studies, limits the power of this study. In summary, Wald et al.'s findings support earlier studies confirming the importance of mineral metabolism as a risk factor for mortality in patients on hemodialysis. However, because of its low statistical power, its lack of analysis of potentially important confounders, and its observational design, the study cannot provide appropriate targets and should not serve as a justification for tolerating mild hyperphosphatemia or hypercalcemia or for overlooking the importance of preventing secondary hyperparathyroidism.}, } @article {pmid18999483, year = {2008}, author = {Cook, BP}, title = {Theory for particle settling and shear-induced migration in thin-film liquid flow.}, journal = {Physical review. E, Statistical, nonlinear, and soft matter physics}, volume = {78}, number = {4 Pt 2}, pages = {045303}, doi = {10.1103/PhysRevE.78.045303}, pmid = {18999483}, issn = {1539-3755}, abstract = {Particles suspended in a film flow can either settle out of the flow, remain well mixed, or even advance faster than the fluid, accumulating at the moving contact line. Recent experiments by Zhou et al. [Phys. Rev. Lett. 94, 117803 (2005)] have demonstrated that these three settling behaviors can be achieved by control of the average particle concentration phi and inclination angle theta . This work presents a theory for determining the settling behavior in the Stokes regime by calculating the depth profile of phi and the depth-averaged velocities of the liquid and particle phases. It is found that shear-induced particle fluxes can lead to an inversely stratified flow, in which the particles move on average faster than the liquid. The theory is directly compared to Zhou et al.'s experimental data, and the implications of stratification for lubrication-type models are also discussed.}, } @article {pmid18989920, year = {2008}, author = {Roy, N and Sproules, S and Bill, E and Weyhermüller, T and Wieghardt, K}, title = {Molecular and electronic structure of the square planar bis(o-amidobenzenethiolato)iron(III) anion and its bis(o-quinoxalinedithiolato)iron(III) analogue.}, journal = {Inorganic chemistry}, volume = {47}, number = {23}, pages = {10911-10920}, doi = {10.1021/ic801109n}, pmid = {18989920}, issn = {1520-510X}, mesh = {Crystallography, X-Ray ; Electron Spin Resonance Spectroscopy ; *Electrons ; Ferric Compounds/*chemistry ; Ligands ; Magnetics ; Quantum Theory ; Spectroscopy, Mossbauer ; Temperature ; }, abstract = {Crystalline purple [PPh4][FeIIIL2] (1), where L2- represents the closed-shell dianion of 4,6-di-tert-butyl-2-[(pentafluorophenyl)amino]benzenethiol, has been synthesized from the reaction of H2L and FeBr2 (2:1) in acetonitrile with excess NEt3, careful, brief exposure of the solution to air, and addition of [PPh4]Br. The monoanion has been shown by X-ray crystallography to be square planar. The oxidation of 1 with 1 equiv of iodine produces the neutral species [FeI(L*)2]0 (2) where (L*)1- represents the one-electron oxidized pi radical anion of L2-. The reaction of H2Land PtCl2 (2:1) and NEt3 in CH3CN in the presence of air produced green, crystalline [PtII(L*)2] (3). From temperature dependent(2-300 K) magnetic susceptibility measurements, it was established that 1 possesses a central intermediate spin ferric ion (SFe) 3/2), whereas neutral 2 has a doublet ground state (St) 1/2) comprising an intermediate spin ferric ion coupled antiferromagnetically to two ligand pi radicals (L*)1- (Srad) 1/2). Complex 3 is diamagnetic. Almeida et al.'s complexes in ref 1, [N(n-Bu)4][FeIII(qdt)2] (A), and [PPh4]2[FeIII2(qdt)4] (B), have been revisited. It is shown here that the square planar anion in mononuclear [FeIII(qdt)2]- also possesses an SFe) 3/2 ground state. The zero-field Mössbauer spectra of 1, 2, A, and B have been recorded and the molecular and electronic structures of all mononuclear iron species have been calculated by density functional theoretical methods.It is shown that the S) 3/2 ground state in 1 and A is lower in energy by 8.5 and 16.6 kcal mol(-1), respectively,than the S) 1/2 state.}, } @article {pmid18988435, year = {2008}, author = {Matt, GE and Vázquez, C}, title = {Anxiety, depressed mood, self-esteem, and traumatic stress symptoms among distant witnesses of the 9/11 terrorist attacks: transitory responses and psychological resilience.}, journal = {The Spanish journal of psychology}, volume = {11}, number = {2}, pages = {503-515}, pmid = {18988435}, issn = {1138-7416}, mesh = {Adolescent ; Anxiety/*diagnosis/psychology ; Cohort Studies ; Depression/*diagnosis/psychology ; Female ; Humans ; Longitudinal Studies ; Male ; *Resilience, Psychological ; *Self Concept ; September 11 Terrorist Attacks/*psychology ; Social Environment ; Stress Disorders, Post-Traumatic/*diagnosis/psychology ; Students/psychology ; Surveys and Questionnaires ; Young Adult ; }, abstract = {Posttraumatic stress related to the September 11, 2001 terrorist attacks and general psychological distress were examined in six cohorts of college students (N=5412) enrolled at an American public university between Spring 2000 and Fall 2002 some 2,500 miles from New York. Consistent with data from Schuster et al.'s (2001) national survey, which used a very low threshold criterion, our findings revealed that 44% of women and 32% of men experienced at least one symptom of posttraumatic stress 6-17 days after the attacks. In contrast to these results, depression levels showed only small differences, and self-esteem and trait anxiety showed no changes. Findings indicate that 9/11-related stress responses among distant witnesses were very mild, transitory and focused in scope, suggesting resilience with respect to broader psychological and psychopathological reactions. Findings are discussed with respect to the role of physical and psychological proximity on the reactions to traumatic events in the general population.}, } @article {pmid18984920, year = {2008}, author = {Weschler, LB}, title = {Comments on Baker et al.'s "Quantitative analysis of serum sodium concentration after prolonged running in the heat".}, journal = {Journal of applied physiology (Bethesda, Md. : 1985)}, volume = {105}, number = {5}, pages = {1692; author reply 1693}, doi = {10.1152/japplphysiol.zdg-8198.2008}, pmid = {18984920}, issn = {8750-7587}, mesh = {Body Water/metabolism ; *Hot Temperature ; Humans ; Models, Biological ; Physical Endurance/*physiology ; Potassium/blood ; *Running ; Sodium/*blood ; Sweating ; Time Factors ; }, } @article {pmid18982111, year = {2008}, author = {Takahashi, Y and Schoenbaum, G and Niv, Y}, title = {Silencing the critics: understanding the effects of cocaine sensitization on dorsolateral and ventral striatum in the context of an actor/critic model.}, journal = {Frontiers in neuroscience}, volume = {2}, number = {1}, pages = {86-99}, pmid = {18982111}, issn = {1662-453X}, support = {R01 DA015718/DA/NIDA NIH HHS/United States ; }, abstract = {A critical problem in daily decision making is how to choose actions now in order to bring about rewards later. Indeed, many of our actions have long-term consequences, and it is important to not be myopic in balancing the pros and cons of different options, but rather to take into account both immediate and delayed consequences of actions. Failures to do so may be manifest as persistent, maladaptive decision-making, one example of which is addiction where behavior seems to be driven by the immediate positive experiences with drugs, despite the delayed adverse consequences. A recent study by Takahashi et al. (2007) investigated the effects of cocaine sensitization on decision making in rats and showed that drug use resulted in altered representations in the ventral striatum and the dorsolateral striatum, areas that have been implicated in the neural instantiation of a computational solution to optimal long-term actions selection called the Actor/Critic framework. In this Focus article we discuss their results and offer a computational interpretation in terms of drug-induced impairments in the Critic. We first survey the different lines of evidence linking the subparts of the striatum to the Actor/Critic framework, and then suggest two possible scenarios of breakdown that are suggested by Takahashi et al.'s (2007) data. As both are compatible with the current data, we discuss their different predictions and how these could be empirically tested in order to further elucidate (and hopefully inch towards curing) the neural basis of drug addiction.}, } @article {pmid18979688, year = {2008}, author = {Carrasco, M and Fuller, S and Ling, S}, title = {Transient attention does increase perceived contrast of suprathreshold stimuli: a reply to Prinzmetal, Long, and Leonhardt (2008).}, journal = {Perception & psychophysics}, volume = {70}, number = {7}, pages = {1151-1164}, pmid = {18979688}, issn = {0031-5117}, support = {R01 EY016200/EY/NEI NIH HHS/United States ; }, mesh = {*Attention ; *Contrast Sensitivity ; Cues ; Differential Threshold ; Humans ; *Visual Perception ; }, abstract = {Carrasco, Ling, and Read (2004) showed that transient attention increases perceived contrast. However, Prinzmetal, Long, and Leonhardt (2008) suggest that for targets of low visibility, observers may bias their response toward the cued location, and they propose a cue-bias explanation for our previous results. Our response is threefold. First, we outline several key methodological differences between the studies that could account for the different results. We conclude that the cue-bias hypothesis is a plausible explanation for Prinzmetal et al.'s (2008) results, given the characteristics of their stimuli, but not for the studies by Carrasco and colleagues, in which the stimuli were suprathreshold (Carrasco, Ling, & Read, 2004; Fuller, Rodriguez, & Carrasco, 2008; Ling & Carrasco, 2007). Second, we conduct a study to show that the stimuli used in our previous studies are not near-threshold, but suprathreshold (Experiment 1, Phase 1). Furthermore, we found an increase in apparent contrast for a high-contrast stimulus when it was precued, but not when it was postcued, providing more evidence against a cue-bias hypothesis (Experiment 1, Phase 2). We also show that the visibility of the stimuli in Prinzmetal et al. (2008) was much lower than that of Carrasco, Ling, and Read, rendering their stimuli susceptible to their cue-bias explanation (Experiment 2). Third, we present a comprehensive summary of all the control conditions used in different labs that have ruled out a cue bias explanation of the appearance studies. We conclude that a cue-bias explanation may operate with near-threshold and low-visibility stimuli, as was the case in Prinzmetal et al. (2008), but that such an explanation has no bearing on studies with suprathreshold stimuli. Consistent with our previous studies, the present data support the claim that attention does alter the contrast appearance of suprathreshold stimuli.}, } @article {pmid18962601, year = {2009}, author = {Law, GU and Rostill-Brookes, H and Goodman, D}, title = {Public stigma in health and non-healthcare students: attributions, emotions and willingness to help with adolescent self-harm.}, journal = {International journal of nursing studies}, volume = {46}, number = {1}, pages = {107-118}, doi = {10.1016/j.ijnurstu.2008.08.014}, pmid = {18962601}, issn = {1873-491X}, mesh = {Adolescent ; Adult ; Analysis of Variance ; Anger ; *Attitude of Health Personnel ; Cross-Sectional Studies ; England ; Female ; Health Knowledge, Attitudes, Practice ; Health Services Needs and Demand ; Helping Behavior ; Humans ; Male ; Nursing Methodology Research ; Public Opinion ; Self-Injurious Behavior/etiology/*prevention & control/psychology ; Social Support ; Statistics, Nonparametric ; *Stereotyping ; Students/*psychology ; Students, Health Occupations/*psychology ; Surveys and Questionnaires ; *Universities ; Young Adult ; }, abstract = {BACKGROUND: For people who self-harm, there is growing evidence to suggest that services and treatment outcomes can be adversely affected by healthcare staffs' stigmatising attitudes and behaviours. To date, the empirical literature has tended to focus on the attitudes of experienced healthcare professionals working with adults who self-harm. Additionally, there has been few theory or model-driven studies to help identify what healthcare students think and feel about young people who self-harm.

OBJECTIVES: The aim of the present study was to explore the way healthcare and non-healthcare students think and feel about adolescent self-harm behaviour using Corrigan et al.'s [Corrigan, P.W., Markowitz, F.E., Watson, A., Rowan, D., Kubiak, M.A., 2003. An attribution model of public discrimination towards people with mental illness. Journal of Health and Social Behaviour 44, 162-179] attribution model of public discrimination towards people with mental illness.

DESIGN: The study was a questionnaire-based, cross-sectional, survey that consisted of two hypothetical vignettes.

SETTINGS: Two universities in England, United Kingdom.

PARTICIPANTS: One hundred and eighty-four final-year students, covering health (medicine, nursing, clinical psychology) and non-health care (physics) professions.

METHODS: Students were presented with vignettes describing a young female who self-harms. Attributions of controllability were experimentally manipulated across the vignette conditions and students were asked to complete self-report questionnaires measuring attitudes towards self-harm, familiarity with self-harm and social desirability.

RESULTS: Consistent with the public discrimination model, students who believed that a young person was responsible for their self-harm reported higher feelings of anger towards them. Anger, in turn, was associated with a belief in the manipulatory nature of the self-harm and with less willingness to help. Perceived risk was found to be associated with higher levels of anxiety and increased support for the use of coercive and segregatory strategies to manage self-harming behaviour. Gender and student type were important influences on public stigma, with both men and medical students reporting more negative attitudes towards self-harm.

CONCLUSIONS: This study provides evidence that a number of factors may adversely affect the care and treatment received by young people who self-harm, namely: students' causal attributions, the gender and profession of healthcare students, and familiarity with self-harm behaviour. To improve the effectiveness of service provision and treatment outcomes for people who self-harm, it is important that health care service providers and teaching institutions consider the implications of these factors when developing staff and services, and base interventions on theoretical models of stigma and discrimination.}, } @article {pmid18959575, year = {2008}, author = {Gomes, L and Livesey, D}, title = {Exploring the link between impulsivity and peer relations in 5- and 6-year-old children.}, journal = {Child: care, health and development}, volume = {34}, number = {6}, pages = {763-770}, doi = {10.1111/j.1365-2214.2008.00878.x}, pmid = {18959575}, issn = {1365-2214}, mesh = {Child ; Child Behavior/*psychology ; Child, Preschool ; Female ; Humans ; *Impulsive Behavior ; *Inhibition, Psychological ; *Interpersonal Relations ; Male ; New South Wales/epidemiology ; *Peer Group ; Rejection, Psychology ; }, abstract = {BACKGROUND: In recent years there has been an increased interest in the behavioural correlates of poor peer relations in childhood. It is now apparent that early poor peer relations are associated with negative future outcomes. The present study investigated whether behaviours that reflect impulsivity or require response inhibition are uniquely linked to children's peer relations.

METHODS: Five- and 6-year-old children's impulsivity was assessed using the teacher-rated impulsivity scale (TRIS), while the stop signal task and a modified version of Manly et al.'s opposite worlds task were employed as measures of response inhibition. In addition, peer relations measures were obtained for each child by asking their peers to indicate on a peer rating scale how much they would like to play with them.

RESULTS: It was found that children's scores on the TRIS correlated significantly with peer relations measures (sociometric preference, peer acceptance and peer rejection) after controlling for gender, age and intelligence. Children rated by their teachers to be more impulsive had poorer peer relations. While there was a significant correlation between TRIS and stop-signal task performance, little relationship was found between either of the response inhibition measures and children's peer relations.

CONCLUSIONS: The findings indicate that impulsivity is associated with children's poor relations with their peers and that this association is dependent upon the measure of impulsivity used. Whereas the more subjective teacher-ratings of impulsiveness did correlate with peer relations, the more objective behavioural measures of response inhibition, (thought to directly measure impulsivity), did not. The difference between these measures needs further investigation. While the data are correlational and causal direction can only be speculated, a practical implication of the finding of an association between impulsivity and peer acceptance is that adoption of strategies to minimize impulsive behaviour may improve the poor peer relations of children.}, } @article {pmid18958981, year = {2008}, author = {Long, W and Millsap, CA}, title = {Fear of AIDS and Homophobia Scales in an ethnic population of university students.}, journal = {The Journal of social psychology}, volume = {148}, number = {5}, pages = {637-640}, doi = {10.3200/SOCP.148.5.637-640}, pmid = {18958981}, issn = {0022-4545}, mesh = {Adult ; Ethnicity/*psychology ; *Fear ; Female ; *HIV Infections ; *Homosexuality ; Humans ; Male ; Midwestern United States ; *Prejudice ; Sex Factors ; }, abstract = {This replication extended R. A. Bouton et al.'s (1987) Fear of AIDS and Homophobia Scales to an ethnic sample of university students in an attempt to understand the relation between the expression of fear of HIV/AIDS and homophobia in ethnic groups. The results of the present study suggest that ethnic groups have a greater fear of HIV/AIDS, as they were more homophobic than the sample surveyed by R. A. Bouton et al. Although the correlation between fear of AIDS and homophobia was significant, results suggest the relation between them is weaker than it was 20 years prior to the present study. The ethnic populations represented in this study did not have greater fear of AIDS by gender. Considering ethnicity, female and male participants showed significant differences in homophobia. As in the original study, male participants were more homophobic than were female participants.}, } @article {pmid18955512, year = {2010}, author = {Beaver, KM and DeLisi, M and Vaughn, MG and Wright, JP}, title = {The intersection of genes and neuropsychological deficits in the prediction of adolescent delinquency and low self-control.}, journal = {International journal of offender therapy and comparative criminology}, volume = {54}, number = {1}, pages = {22-42}, doi = {10.1177/0306624X08325349}, pmid = {18955512}, issn = {1552-6933}, mesh = {Adolescent ; *Cognition Disorders/diagnosis/epidemiology/genetics ; Female ; *Genotype ; Humans ; Juvenile Delinquency/*psychology/*statistics & numerical data ; Life Change Events ; Male ; Monoamine Oxidase/*genetics ; *Neuropsychological Tests ; Predictive Value of Tests ; *Self Efficacy ; Severity of Illness Index ; *Social Control, Informal ; *Social Environment ; }, abstract = {Gottfredson and Hirschi's A General Theory of Crime, Moffitt's developmental taxonomy theory, and Caspi et al.'s Gene x Environment study are three of the most influential pieces of contemporary criminological scholarship. Even so, there has been little attempt to integrate and empirically assess these three perspectives simultaneously. This article addresses this gap in the literature by analyzing phenotypic and genotypic data from the National Longitudinal Study of Adolescent Health (Add Health). The results revealed that all three perspectives have considerable empirical support, where neuropsychological deficits interact with the MAOA genotype to predict adolescent delinquency and levels of self-control for White males. The theoretical implications of the findings are noted.}, } @article {pmid18951982, year = {2009}, author = {Chang, C and Cunningham, JP and Glover, GH}, title = {Influence of heart rate on the BOLD signal: the cardiac response function.}, journal = {NeuroImage}, volume = {44}, number = {3}, pages = {857-869}, pmid = {18951982}, issn = {1095-9572}, support = {T32-GM063495/GM/NIGMS NIH HHS/United States ; P41-RR09784/RR/NCRR NIH HHS/United States ; T32 GM063495/GM/NIGMS NIH HHS/United States ; P41 RR009784/RR/NCRR NIH HHS/United States ; F31 AG032168/AG/NIA NIH HHS/United States ; }, mesh = {Adult ; *Artifacts ; Brain/*physiology ; Brain Mapping/*methods ; Evoked Potentials/*physiology ; Female ; Heart Rate/*physiology ; Humans ; Magnetic Resonance Imaging/*methods ; Male ; Reproducibility of Results ; Sensitivity and Specificity ; }, abstract = {It has previously been shown that low-frequency fluctuations in both respiratory volume and cardiac rate can induce changes in the blood-oxygen level dependent (BOLD) signal. Such physiological noise can obscure the detection of neural activation using fMRI, and it is therefore important to model and remove the effects of this noise. While a hemodynamic response function relating respiratory variation (RV) and the BOLD signal has been described [Birn, R.M., Smith, M.A., Jones, T.B., Bandettini, P.A., 2008b. The respiration response function: The temporal dynamics of fMRI signal fluctuations related to changes in respiration. Neuroimage 40, 644-654.], no such mapping for heart rate (HR) has been proposed. In the current study, the effects of RV and HR are simultaneously deconvolved from resting state fMRI. It is demonstrated that a convolution model including RV and HR can explain significantly more variance in gray matter BOLD signal than a model that includes RV alone, and an average HR response function is proposed that well characterizes our subject population. It is observed that the voxel-wise morphology of the deconvolved RV responses is preserved when HR is included in the model, and that its form is adequately modeled by Birn et al.'s previously-described respiration response function. Furthermore, it is shown that modeling out RV and HR can significantly alter functional connectivity maps of the default-mode network.}, } @article {pmid18951512, year = {2008}, author = {Bonmatí, A and Arsuaga, JL and Lorenzo, C}, title = {Revisiting the developmental stage and age-at-death of the "Mrs. Ples" (Sts 5) and Sts 14 specimens from Sterkfontein (South Africa): do they belong to the same individual?.}, journal = {Anatomical record (Hoboken, N.J. : 2007)}, volume = {291}, number = {12}, pages = {1707-1722}, doi = {10.1002/ar.20795}, pmid = {18951512}, issn = {1932-8494}, mesh = {Aging/physiology ; Animals ; Anthropology, Physical/methods ; Anthropometry/methods ; Biological Evolution ; Bone Development/*physiology ; Bone and Bones/*anatomy & histology ; Female ; Hominidae/*anatomy & histology/*growth & development ; Longevity/physiology ; Paleontology/methods ; Pan troglodytes/anatomy & histology/growth & development ; *Skeleton ; Skull/anatomy & histology/growth & development ; South Africa ; Species Specificity ; Spine/anatomy & histology/growth & development ; }, abstract = {During the 1947 fieldwork season, Member 4 (2-3 My) of the South African Sterkfontein site yielded two important Australopithecus africanus fossils: a cranium popularly nicknamed "Mrs. Ples" (Sts 5), and a partial skeleton (Sts 14). Previous reports have proposed that Sts 5 was a nonfully grown adolescent individual (Thackeray et al., S Afr J Sci 2002a;98:21-22), and that Sts 14 was a sub-adult specimen (according to various signs of immaturity in the skeleton) (Berge and Gommery, C R Acad Sci Paris, Sciences de la terre et des planètes 1999;329:227-232; Häusler and Berger, J Hum Evol, 2001;40:411-417; Thackeray et al., S Afr J Sci, 2002b;98:211-212). It was subsequently proposed that these fossils actually belonged to the same individual (Thackeray et al., S Afr J Sci, 2002b;98:211-212), a proposition supported by their spatial positions within the site. The present work attempts to revise these different assertions. The results obtained: (i) show that the Sts 5 fossil represents a fully grown adult cranium; (ii) provide new evidence of immaturity in the Sts 14 skeletal elements (sustaining the proposed young adult age of this specimen), and (iii) suggest that although the revised ages-at-death for these fossils are partially compatible, there is no evidence to support the idea that they represent a single individual. Finally, the encephalization quotient associated with a hypothetical union of Sts 5 and Sts 14 (calculated using data from both specimens) lies between the upper and lower limits of the currently estimated range for this species and H. habilis, respectively.}, } @article {pmid18941656, year = {2008}, author = {Davies, RP and Giménez, MA and Patel, L and White, AJ}, title = {Aluminium complexes with thio-phosphorus ligands: syntheses and characterisations of [Al(2)(CyPS(3))(2)(CyPHS(2))(2)] and [Al(S(2)PPh(2))(3)].}, journal = {Dalton transactions (Cambridge, England : 2003)}, volume = {}, number = {42}, pages = {5705-5707}, doi = {10.1039/b813427h}, pmid = {18941656}, issn = {1477-9226}, abstract = {The novel aluminium complexes [Al(2)(CyPS(3))(2)(CyPHS(2))(2)] and [Al(S(2)PPh(2))(3)] have been prepared as potential models for alumino-thiophosphonate based materials; [Al(2)(CyPS(3))(2)(CyPHS(2))(2)] is the first example of a primary dithiophosphinate to be characterised in the solid state.}, } @article {pmid18938762, year = {2008}, author = {Guez, D and Miller, RR}, title = {Blocking and pseudoblocking: the reply of Rattus norvegicus to Apis mellifera.}, journal = {Quarterly journal of experimental psychology (2006)}, volume = {61}, number = {8}, pages = {1186-1198}, pmid = {18938762}, issn = {1747-0218}, support = {R01 MH033881/MH/NIMH NIH HHS/United States ; 33881//PHS HHS/United States ; }, mesh = {Adaptation, Physiological ; Animals ; Bees ; *Behavior, Animal ; Female ; *Learning ; Male ; Rats ; Rats, Sprague-Dawley ; }, abstract = {Blaser, Couvillon, and Bitterman (2006) presented data obtained with honeybees that in principle challenged all traditional interpretations of blocking. They administered A + followed by either A + or + alone (where + indicates an unconditioned stimulus) and then tested on X. They observed less responding to X when they administered A + than when + alone was administered, a phenomenon they called "pseudoblocking". Here we examined pseudoblocking in a rat fear-conditioning preparation. In Experiment 1, using a control procedure that was similar to our usual blocking control, we obtained conventional blocking but failed to observe pseudoblocking in our analogue to Blaser et al.'s procedure. In Experiment 2, we used Blaser et al.'s control procedure and again failed to observe the pseudoblocking effect with rats when we used the experimental context as an analogue to the honeybee feeder used by Blaser et al. After reviewing their protocol and previously published studies from their laboratory, we hypothesized that the feeder that they treated as a training context probably served as a punctate cue. We also tested this possibility in Experiment 2, using a punctate cue as a surrogate feeder, and were now able to reproduce their pseudoblocking phenomena. Our results are consistent with a simple overshadowing account of pseudoblocking, within the framework of existing theories of associative learning, which is not applicable to the conventional blocking paradigm. Thus, blocking remains a real phenomenon that must be addressed by models of associative learning.}, } @article {pmid18854130, year = {2008}, author = {Hirasawa, R and Feil, R}, title = {A KRAB domain zinc finger protein in imprinting and disease.}, journal = {Developmental cell}, volume = {15}, number = {4}, pages = {487-488}, doi = {10.1016/j.devcel.2008.09.006}, pmid = {18854130}, issn = {1878-1551}, mesh = {Animals ; Diabetes Mellitus/*genetics ; *Genomic Imprinting ; Humans ; Infant, Newborn ; Mice ; Mice, Knockout ; Mutation ; Protein Structure, Tertiary ; Repressor Proteins/*genetics/metabolism ; }, abstract = {The monoallelic expression of imprinted genes is regulated by DNA methylation marks that originate from the oocyte or sperm. Li et al. (2008) show in this issue of Developmental Cell that the KRAB zinc finger protein Zfp57 contributes to the embryonic maintenance of these imprints. At one locus, Zfp57 is also involved in imprint establishment. These findings provide a mechanistic interpretation for Mackay et al.'s recently reported ZFP57 mutations in patients with transient neonatal diabetes.}, } @article {pmid18852724, year = {2008}, author = {Serra, E}, title = {Duloxetine and pregabalin: safe and effective for the long-term treatment of fibromyalgia?.}, journal = {Nature clinical practice. Neurology}, volume = {4}, number = {11}, pages = {594-595}, doi = {10.1038/ncpneuro0936}, pmid = {18852724}, issn = {1745-8358}, abstract = {This Practice Point commentary discusses the first two trials of long-term drug treatment in fibromyalgia. In Russell et al.'s study, 33% of patients receiving 6-month treatment with 60 mg/day duloxetine responded to therapy; the number needed to treat was seven. In the three treatment arms, 15% (60 mg/day duloxetine), 27% (120 mg/day duloxetine) and 13% (placebo) of patients discontinued treatment because of adverse events (the most common being nausea [24%] and fatigue [14%]). In Crofford et al.'s study, 32% of patients who received pregabalin had loss of therapeutic response, compared with 61% of patients treated with placebo. The discontinuation rate due to adverse events (dizziness in 36% of cases and somnolence in 22%) during the randomized treatment phase was 16% with pregabalin and 7% with placebo. This commentary discusses the implications of these trials for clinical practice and considers areas for future research in the field. In view of the current results, duloxetine and pregabalin could be administered together and as part of multimodal and multidisciplinary therapy, but treatment should 'start low and go slow'.}, } @article {pmid18846247, year = {2008}, author = {Fink, RB and Bartlett, MR and Lowery, JS and Linebarger, MC and Schwartz, MF}, title = {Aphasic speech with and without SentenceShaper: Two methods for assessing informativeness.}, journal = {Aphasiology}, volume = {22}, number = {7-8}, pages = {679-690}, pmid = {18846247}, issn = {0268-7038}, support = {R01 HD043991/HD/NICHD NIH HHS/United States ; }, abstract = {BACKGROUND: SentenceShaper((R)) (SSR) is a computer program that is for speech what a word-processing program is for written text; it allows the user to record words and phrases, play them back, and manipulate them on-screen to build sentences and narratives. A recent study demonstrated that when listeners rated the informativeness of functional narratives produced by chronic aphasic speakers with and without the program they gave higher informativeness ratings to the language produced with the aid of the program (Bartlett, Fink, Schwartz, & Linebarger, 2007). Bartlett et al. (2007) also compared unaided (spontaneous) narratives produced before and after the aided version of the narrative was obtained. In a subset of comparisons, the sample created after was judged to be more informative; they called this "topic-specific carryover". AIMS: (1) To determine whether differences in informativeness that Bartlett et al.'s listeners perceived are also revealed by Correct Information Unit (CIU) analysis (Nicholas & Brookshire, 1993)-a well studied, objective method for measuring informativeness-and (2) to demonstrate the usefulness of CIU analysis for samples of this type. METHODS #ENTITYSTARTX00026; PROCEDURES: A modified version of the CIU analysis was applied to the speech samples obtained by Bartlett et al. (2007). They had asked five individuals with chronic aphasia to create functional narratives on two topics, under three conditions: Unaided ("U"), Aided ("SSR"), & Post-SSR Unaided ("Post-U"). Here, these samples were analysed for differences in % CIUs across conditions. Linear associations between listener judgements and CIU measures were evaluated with bivariate correlations and multiple regression analysis. OUTCOMES #ENTITYSTARTX00026; RESULTS: (1) The aided effect was confirmed: samples produced with SentenceShaper had higher % CIUs, in most cases exceeding 90%. (2) There was little CONCLUSIONS: That the percentage of CIUs was higher in SSR-aided samples than in unaided samples confirms the central finding in Bartlett et al. (2007), based on subjective judgements, and thus extends the evidence that aided effects from SentenceShaper are demonstrable across a range of measures, stimuli and participants (cf. Linebarger, Schwartz, Romania, Kohn, & Stephens, 2000). The data also attest to the effectiveness of the CIU analysis for quantifying differences in the informativeness of aphasic speech with and without SentenceShaper; and they support prior studies that have shown that CIU measures correlate with the informativeness ratings of unfamiliar listeners.}, } @article {pmid18845356, year = {2009}, author = {Verheijde, JL and Rady, MY and McGregor, JL and Friederich-Murray, C}, title = {Enforcement of presumed-consent policy and willingness to donate organs as identified in the European Union Survey: the role of legislation in reinforcing ideology in pluralistic societies.}, journal = {Health policy (Amsterdam, Netherlands)}, volume = {90}, number = {1}, pages = {26-31}, doi = {10.1016/j.healthpol.2008.08.008}, pmid = {18845356}, issn = {0168-8510}, mesh = {Data Collection ; European Union ; Health Policy/*legislation & jurisprudence ; Humans ; *Presumed Consent ; Tissue and Organ Procurement/*legislation & jurisprudence ; }, abstract = {To increase the supply of transplantable organs, some European Union (EU) countries have begun implementing and enforcing presumed consent policies for organ donation. Mossialos and colleagues performed an analysis of samples of citizens in 15 EU countries and found that legislation, enforcement, and awareness of presumed consent policies for organ donation increase people's willingness to donate their own organs and those of a deceased relative. The authors concluded that, in countries with enforced presumed consent, citizens are willing to donate because they accept organ donation as an ideology. This ideology originates in the thinking that organ donation is an implicit communal contract i.e., a mechanism by which individuals pay back society for the inclusion and social support that they have already experienced and hope to experience in the future. Acceptance of this ideology enhances people's willingness to donate organs and the efficiency in pursuing this collective action, thus, paving the way toward increased paternalism in society. We highlight some potential biases that may have been incorporated in the survey design and in Mossialos et al.'s conclusions, including (1) how the survey questions were constructed, (2) whether sufficient information was communicated about organ procurement practices in heart-beating and non-heart-beating donation before participants responded to the survey, and (3) whether respondents' knowledge about donation legislation can be equated with understanding of processes involved in organ donation. We address the consequences of using legislative authority to enforce the ideology of organ donation, thereby superseding the varying moral values, beliefs, and attitudes about human life and culture that are inherent in multicultural societies.}, } @article {pmid18826072, year = {2008}, author = {Stansbury, K and Schumacher, M}, title = {An exploration of mental health literacy among African American clergy.}, journal = {Journal of gerontological social work}, volume = {51}, number = {1-2}, pages = {126-142}, doi = {10.1080/01634370801967596}, pmid = {18826072}, issn = {0163-4372}, mesh = {Adult ; Black or African American/*statistics & numerical data ; Aged ; Clergy/*statistics & numerical data ; *Cognition ; Cognition Disorders/ethnology ; Counseling ; Culture ; *Educational Status ; *Health Knowledge, Attitudes, Practice ; Humans ; *Mental Health ; Mental Health Services/*supply & distribution ; Middle Aged ; Pastoral Care/*methods ; Religion ; Rural Population ; Stress, Psychological/ethnology/psychology ; Urban Population ; }, abstract = {The purpose of this qualitative study was to explore African American clergy's mental health literacy with older congregants 60 years of age and older. Using a grounded theory approach, we recruited a purposive sample of 9 African American clergy representing diverse ages, denominations, locales, and educational levels. Data was coded and classified according to Kevin's (1976) typology of pastoral counseling and Jorm et al.'s (1997) conceptual model of mental health literacy. Findings from data analysis revealed study respondents were adherents of Kevin's Religious-Community (R-C) model. Additionally, the following themes emerged: loss of cognitive functioning, psychosocial stressors, religiosity, and appreciation for professional assistance, cultural barriers, and key informants/familiarity with formal mental health providers which partially maps onto Jorm et al.'s conceptual model of mental health literacy.}, } @article {pmid18813233, year = {2008}, author = {Crews, DC and Jaar, BG}, title = {Racial differences in chronic kidney disease incidence and progression among individuals with HIV.}, journal = {Nature clinical practice. Nephrology}, volume = {4}, number = {12}, pages = {652-653}, pmid = {18813233}, issn = {1745-8331}, support = {KL2 RR025006/RR/NCRR NIH HHS/United States ; L60 MD003031/MD/NIMHD NIH HHS/United States ; }, abstract = {This Practice Point commentary discusses the findings of Lucas et al.'s longitudinal cohort study of chronic kidney disease (CKD) in African American and white individuals with HIV. The study found that--compared with whites--African Americans had a slightly increased risk of incident CKD, but markedly increased rates of estimated glomerular filtration rate decline and progression to end-stage renal disease. This commentary details the clinical implications and limitations of these findings in the context of known racial differences in CKD prevalence and progression to end-stage renal disease in the general population and highlights the importance of screening high-risk HIV patients for kidney disease. CKD is common among HIV patients, and-as in the general population-has a more-aggressive course among African Americans than whites.}, } @article {pmid18808263, year = {2008}, author = {Turner, RN and Hewstone, M and Voci, A and Vonofakou, C}, title = {A test of the extended intergroup contact hypothesis: the mediating role of intergroup anxiety, perceived ingroup and outgroup norms, and inclusion of the outgroup in the self.}, journal = {Journal of personality and social psychology}, volume = {95}, number = {4}, pages = {843-860}, doi = {10.1037/a0011434}, pmid = {18808263}, issn = {0022-3514}, mesh = {Adolescent ; Adult ; Anxiety/*psychology ; *Attitude ; Female ; Humans ; *Interpersonal Relations ; Male ; *Psychological Tests ; *Psychological Theory ; *Self Concept ; *Social Perception ; }, abstract = {S. C. Wright, A. Aron, T. McLaughlin-Volpe, and S. A. Ropp (1997) proposed that the benefits associated with cross-group friendship might also stem from vicarious experiences of friendship. Extended contact was proposed to reduce prejudice by reducing intergroup anxiety, by generating perceptions of positive ingroup and outgroup norms regarding the other group, and through inclusion of the outgroup in the self. This article documents the first test of Wright et al.'s model, which used structural equation modeling among two independent samples in the context of South Asian-White relations in the United Kingdom. Supporting the model, all four variables mediated the relationship between extended contact and outgroup attitude, controlling for the effect of direct contact. A number of alternative models were ruled out, indicating that the four mediators operate concurrently rather than predicting one another.}, } @article {pmid18803089, year = {2008}, author = {Smith, PA and Baber, C and Hunter, J and Butler, M}, title = {Measuring team skills in crime scene investigation: exploring ad hoc teams.}, journal = {Ergonomics}, volume = {51}, number = {10}, pages = {1463-1488}, doi = {10.1080/00140130802248076}, pmid = {18803089}, issn = {0014-0139}, mesh = {Crime ; Forensic Sciences/*organization & administration ; *Group Processes ; Humans ; Interprofessional Relations ; Police/*organization & administration ; }, abstract = {The purpose of this study was to measure the team skills of operational crime scene examiners (CSEs). The techniques used were based on established methods and helped to gain a greater understanding of the domain of forensic investigation. The research begins with a hierarchical task analysis and then adapts pre-established methods for measuring the performance of CSEs in four UK Police Forces. The process supports comparison between prescribed methods of 'good practice' and real world practice. This has allowed the identification of the distributed skills and tasks of the CSE. Using Annett et al.'s HTA(T), crime scene examination can be categorised and the communications and coordination structures occurring between teams investigating a burglary considered. This makes it possible to generalise the method to situations involving ad hoc teams.}, } @article {pmid18797429, year = {2008}, author = {Rosendaal, FR}, title = {Hormone replacement therapy and thrombotic risk: beauty is only skin deep.}, journal = {Nature clinical practice. Cardiovascular medicine}, volume = {5}, number = {11}, pages = {684-685}, doi = {10.1038/ncpcardio1346}, pmid = {18797429}, issn = {1743-4300}, mesh = {Administration, Cutaneous ; Administration, Oral ; Breast Neoplasms/chemically induced ; Coronary Disease/chemically induced ; Drug Administration Schedule ; Estrogen Replacement Therapy/*adverse effects ; Estrogens/administration & dosage/*adverse effects ; Female ; Humans ; Meta-Analysis as Topic ; Risk Assessment ; Venous Thrombosis/*chemically induced ; }, abstract = {In their meta-analysis of studies on hormone replacement therapy (HRT), Canonico and colleagues reported that the risk of venous thrombosis was increased by 2.5-fold in current users of oral preparations, while the risk was not increased in those using transdermal hormone patches. Several large trials have shown that oral estrogens do not protect against, and might even increase the risk of, coronary heart disease, and slightly elevates the risk of breast cancer after prolonged use. On the basis of these results, HRT is no longer indicated for long-term use. Canonico et al.'s meta-analysis shows that when used over a short period of time to alleviate the symptoms of menopause, skin patches are likely to be safer than orally-administered hormones with respect to the risk of venous thrombosis, which is a potentially fatal complication.}, } @article {pmid18784263, year = {2008}, author = {Mizuguchi, Y and Chen, J and Seshan, SV and Poppas, DP and Szeto, HH and Felsen, D}, title = {A novel cell-permeable antioxidant peptide decreases renal tubular apoptosis and damage in unilateral ureteral obstruction.}, journal = {American journal of physiology. Renal physiology}, volume = {295}, number = {5}, pages = {F1545-53}, pmid = {18784263}, issn = {1931-857X}, support = {P01-DA-08924/DA/NIDA NIH HHS/United States ; R-01-DK-58355/DK/NIDDK NIH HHS/United States ; R01-DA-073595/DA/NIDA NIH HHS/United States ; }, mesh = {8-Hydroxy-2'-Deoxyguanosine ; Animals ; Antioxidants/pharmacology/therapeutic use ; Apoptosis/*drug effects ; Cell Proliferation/drug effects ; Cytokines/genetics/metabolism ; Deoxyguanosine/analogs & derivatives/metabolism ; Disease Models, Animal ; Enzyme-Linked Immunosorbent Assay ; Fibroblasts/drug effects/metabolism/pathology ; Gene Expression/drug effects ; Heme Oxygenase-1/metabolism ; Intermediate Filament Proteins/metabolism ; Kidney/*drug effects/metabolism/pathology ; Macrophages/drug effects/metabolism/pathology ; Oligopeptides/pharmacology/*therapeutic use ; Oxidative Stress/drug effects ; Rats ; Rats, Sprague-Dawley ; Receptors, CCR1/genetics/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Transcription Factor RelA/genetics/metabolism ; Transforming Growth Factor beta/genetics/metabolism ; Ureteral Obstruction/*drug therapy/metabolism/pathology ; p38 Mitogen-Activated Protein Kinases/genetics/metabolism ; }, abstract = {Unilateral ureteral obstruction (UUO) is characterized by decreases in renal function, increased interstitial fibrosis, tubular apoptosis, and cellular infiltration. It has been suggested that inhibition of tubular apoptosis may protect against renal damage in obstruction. We have recently developed a series of peptides which are concentrated in the inner mitochondrial membrane and prevent cell death. These peptides are also active in vivo, in myocardial infraction, ischemic brain injury, and amyotrophic lateral sclerosis models. We therefore used SS-31, a prototype of these peptides, and assessed its effects on renal damage and oxidative stress in a 14-day obstruction model. SS-31 (1 or 3 mg/kg) or saline was given 1 day before and throughout the 14 days of obstruction. Kidneys were harvested and assessed for apoptosis (terminal transferase-dUTP-nick-end labeling, caspase 3 expression), fibrosis (trichrome staining), macrophage infiltration, fibroblast expression (immunoperoxidase), and oxidative damage (8-OH deoxyguanosine and heme oxygenase-1 expression), cytokines, and signaling pathways (transforming growth factor-beta, CCR-1, p38-MAPK, NF-kappaB). SS-31 significantly attenuated the effects of obstruction on all aspects of renal damage which were examined, with both the 1 and 3 mg/kg doses showing efficacy. We noted increased oxidative stress in obstruction, which was also attenuated by SS-31 treatment. Signaling via NF-kappaB and p38 MAPK pathways were both affected by SS-31 treatment. This study provides a proof of concept that peptides which protect mitochondria in vitro can provide protection from renal damage in a UUO model. The mechanism by which protection is afforded requires further studies both in vitro and in vivo.}, } @article {pmid18781659, year = {2009}, author = {Rytwinski, NK and Fresco, DM and Heimberg, RG and Coles, ME and Liebowitz, MR and Cissell, S and Stein, MB and Hofmann, SG}, title = {Screening for social anxiety disorder with the self-report version of the Liebowitz Social Anxiety Scale.}, journal = {Depression and anxiety}, volume = {26}, number = {1}, pages = {34-38}, doi = {10.1002/da.20503}, pmid = {18781659}, issn = {1520-6394}, mesh = {Adolescent ; Adult ; Aged ; Anxiety Disorders/diagnosis/epidemiology/psychology ; Comorbidity ; Cross-Sectional Studies ; Depressive Disorder/diagnosis/epidemiology/psychology ; Diagnosis, Differential ; Female ; Humans ; Male ; *Mass Screening ; Middle Aged ; Pennsylvania ; Personality Inventory/*statistics & numerical data ; Phobic Disorders/classification/*diagnosis/epidemiology/psychology ; Psychometrics ; Reference Values ; Reproducibility of Results ; Young Adult ; }, abstract = {OBJECTIVE: This study examined whether the self-report version of the Liebowitz Social Anxiety Scale (LSAS-SR) could accurately identify individuals with social anxiety disorder and individuals with the generalized subtype of social anxiety disorder. Furthermore, the study sought to determine the optimal cutoffs for the LSAS-SR for identifying patients with social anxiety disorder and its generalized subtype.

METHODS: Two hundred and ninety-one patients with clinician-assessed social anxiety disorder (240 with generalized social anxiety disorder) and 53 control participants who were free from current Axis-1 disorders completed the LSAS-SR.

RESULTS: Receiver Operating Characteristic analyses revealed that the LSAS-SR performed well in identifying participants with social anxiety disorder and generalized social anxiety disorder. Consistent with Mennin et al.'s [2002: J Anxiety Disord 16:661-673] research on the clinician-administered version of the LSAS, cutoffs of 30 and 60 on the LSAS-SR provided the best balance of sensitivity and specificity for classifying participants with social anxiety and generalized social anxiety disorder, respectively.

CONCLUSIONS: The LSAS-SR may be an accurate and cost-effective way to identify and subtype patients with social anxiety disorder, which could help increase the percentage of people who receive appropriate treatment for this debilitating disorder.}, } @article {pmid18729600, year = {2008}, author = {Oberauer, K and Oaksford, M}, title = {What must a psychological theory of reasoning explain? Comment on Barrouillet, Gauffroy, and Lecas (2008).}, journal = {Psychological review}, volume = {115}, number = {3}, pages = {773-8; discussion 778}, doi = {10.1037/0033-295X.115.3.773}, pmid = {18729600}, issn = {0033-295X}, mesh = {Humans ; *Problem Solving ; *Psychological Theory ; }, abstract = {In this comment, it is argued that the modification of mental models theory of conditional inference proposed by P. Barrouillet, C. Gauffroy, and J.-F. Lecas to deal with truth value gaps merely patches up a problem in the theory, rather than accomplishing the fundamental and systematic revision that is necessary. It is argued that P. Barrouillet et al.'s modified mental model theory fails to meet the criteria of good theory of reasoning by invoking an algorithmic-level distinction to resolve a failing in the computational-level theory of the task.}, } @article {pmid18718671, year = {2008}, author = {Norris, AE and Aroian, KJ}, title = {Assessing reliability and validity of the Arabic language version of the Post-traumatic Diagnostic Scale (PDS) symptom items.}, journal = {Psychiatry research}, volume = {160}, number = {3}, pages = {327-334}, pmid = {18718671}, issn = {0165-1781}, support = {R01 NR008504/NR/NINR NIH HHS/United States ; NR 008504/NR/NINR NIH HHS/United States ; }, mesh = {Adult ; Anxiety Disorders/diagnosis/epidemiology ; Arabs/psychology/*statistics & numerical data ; Depressive Disorder/diagnosis/epidemiology ; Diagnostic and Statistical Manual of Mental Disorders ; Emigration and Immigration/statistics & numerical data ; Female ; Humans ; Iraq/ethnology ; Life Change Events ; Personality Inventory/statistics & numerical data ; Psychiatric Status Rating Scales/*statistics & numerical data ; Psychometrics ; Refugees/psychology/statistics & numerical data ; Reproducibility of Results ; Severity of Illness Index ; Sex Factors ; Stress Disorders, Post-Traumatic/*diagnosis/epidemiology/psychology ; Surveys and Questionnaires ; Translations ; United States/epidemiology ; }, abstract = {Arab immigrant women are vulnerable to post-traumatic stress disorder (PTSD) because of gender, higher probability of being exposed to war-related violence, traditional cultural values, and immigration stressors. A valid and reliable screen is needed to assess PTSD incidence in this population. This study evaluated the reliability and validity of an Arabic language version of the symptom items in Foa et al.'s [Foa, E.B., Cashman, L., Jaycox, L., and Perry, K. 1997. The validation of a self report measure of posttraumatic stress disorder: the Posttraumatic Diagnostic Scale. Psychological Assessment 9(4), 445-451]. Post-traumatic Diagnostic Scale (PDS) in a sample of Arab immigrant women (n=453). Reliability was supported by Cronbach's alpha values for the Arabic language version (0.93) and its subscales (0.77-0.91). Results of group comparisons supported validity: Women who had lived in a refugee camp or emigrated from Iraq - a country where exposure to war and torture is common - were exhibiting depressive symptoms (Center for Epidemiological Studies-Depression Scale (CES-D) score above 18), or reported moderately to severely impaired functioning had significantly higher mean PDS total and symptom subscale scores than women who had not had these experiences or were not exhibiting depressive symptoms. Scores on the PDS and its subscales were also positively correlated with the Profile of Mood States (POMS) depression and anxiety subscales and negatively correlated with the POMS vigor subscale (r=-.29 to-.39).}, } @article {pmid18707261, year = {2001}, author = {Clark, JS and Lewis, M and Horvath, L}, title = {Invasion by extremes: population spread with variation in dispersal and reproduction.}, journal = {The American naturalist}, volume = {157}, number = {5}, pages = {537-554}, doi = {10.1086/319934}, pmid = {18707261}, issn = {1537-5323}, abstract = {For populations having dispersal described by fat-tailed kernels (kernels with tails that are not exponentially bounded), asymptotic population spread rates cannot be estimated by traditional models because these models predict continually accelerating (asymptotically infinite) invasion. The impossible predictions come from the fact that the fat-tailed kernels fitted to dispersal data have a quality (nondiscrete individuals and, thus, no moment-generating function) that never applies to data. Real organisms produce finite (and random) numbers of offspring; thus, an empirical moment-generating function can always be determined. Using an alternative method to estimate spread rates in terms of extreme dispersal events, we show that finite estimates can be derived for fat-tailed kernels, and we demonstrate how variable reproduction modifies these rates. Whereas the traditional models define spread rate as the speed of an advancing front describing the expected density of individuals, our alternative definition for spread rate is the expected velocity for the location of the furthest-forward individual in the population. The asymptotic wave speed for a constant net reproductive rate R0 is approximated as (1/T)(piuR)/2)(1/2) m yr(-1), where T is generation time, and u is a distance parameter (m2) of Clark et al.'s 2Dt model having shape parameter p = 1. From fitted dispersal kernels with fat tails and infinite variance, we derive finite rates of spread and a simple method for numerical estimation. Fitted kernels, with infinite variance, yield distributions of rates of spread that are asymptotically normal and, thus, have finite moments. Variable reproduction can profoundly affect rates of spread. By incorporating the variance in reproduction that results from variable life span, we estimate much lower rates than predicted by the standard approach, which assumes a constant net reproductive rate. Using basic life-history data for trees, we show these estimated rates to be lower than expected from previous analytical models and as interpreted from paleorecords of forest spread at the end of the Pleistocene. Our results suggest reexamination of past rates of spread and the potential for future response to climate change.}, } @article {pmid18704756, year = {2008}, author = {Bloem, EF and van Zuuren, FJ and Koeneman, MA and Rapkin, BD and Visser, MR and Koning, CC and Sprangers, MA}, title = {Clarifying quality of life assessment: do theoretical models capture the underlying cognitive processes?.}, journal = {Quality of life research : an international journal of quality of life aspects of treatment, care and rehabilitation}, volume = {17}, number = {8}, pages = {1093-1102}, pmid = {18704756}, issn = {0962-9343}, mesh = {Adaptation, Psychological ; Adult ; Aged ; Aged, 80 and over ; *Cognition ; Cognition Disorders/*psychology ; Female ; Humans ; Interviews as Topic ; Male ; Middle Aged ; Models, Psychological ; Models, Theoretical ; Neoplasms/*psychology ; Psychometrics ; Qualitative Research ; Quality of Life/*psychology ; Stress, Psychological/*psychology ; Surveys and Questionnaires ; }, abstract = {OBJECTIVE: To develop an analysis scheme capturing the cognitive processes underlying QoL assessment to increase our understanding on how to interpret responses to QoL items. Tourangeau et al.'s (The psychology of survey response, 2000) and Rapkin and Schwartz' (Health Qual Life Outcomes 2:14, 2004) cognitive process models form the basis for this analysis scheme.

METHODS: We conducted think aloud interviews with six cancer patients prior to and following radiotherapy to elicit the cognitive processes underlying the assessment of 7 EORTC QLQ-C30 items. Content analysis was carried out by two to four researchers independently. Eighty text fragments were analyzed inductively and combined in an iterative process with deductive analyses based on both models.

RESULTS: We have developed a comprehensive analysis scheme feasible for analyzing the cognitive processes underlying QoL assessment qualitatively. All cognitive components of both models could be distinguished in our data. The cognitive component 'reporting and response selection' needed extension to fully capture the cognitive processes used.

CONCLUSION: The two models combined are useful in describing the cognitive processes cancer patients use in answering QoL items, and as such facilitate insight into patients' self-reported QoL assessments. Interestingly, the content of the cognitive processes not only differed between patients but also between items within patients and over time.}, } @article {pmid18696096, year = {2009}, author = {Cavallini, GM and Martini, A and Campi, L and Forlini, M}, title = {Bottle cork and cap injury to the eye: a review of 34 cases.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {247}, number = {4}, pages = {445-450}, pmid = {18696096}, issn = {1435-702X}, mesh = {Adult ; Aged ; Aged, 80 and over ; *Alcoholic Beverages ; Eye Injuries/*epidemiology/etiology/surgery ; Female ; Follow-Up Studies ; Humans ; Hyphema/epidemiology/etiology/surgery ; Male ; Middle Aged ; *Product Packaging ; Retrospective Studies ; Seasons ; Vision Disorders/*epidemiology/etiology/surgery ; Visual Acuity/physiology ; Wounds, Nonpenetrating/*epidemiology/etiology/surgery ; Young Adult ; }, abstract = {AIM: To describe our series of bottle cork and cap injuries to the eye in order to report the visual impairment and clinical outcomes observed in 34 cases over an 8-year period.

METHODS: Retrospective review of the database of the Ophthalmology Institute of Modena from January 1999 to September 2007. All patients presented with closed-globe injury according to Kuhn et al.'s classification. All the cases were caused by sparkling wine: white in 24 cases and red in ten cases.

RESULTS: The incidence varied between six and two cases a year (average 3.89). Bottle cork and cap injuries represent 11% of all injuries admitted to our department in the period considered in our series. In details: nine patients recovered totally, 22 patients recovered partially, three patients had a severe visual outcome (
CONCLUSIONS: To our knowledge, this is the largest series of bottle cork and cap injuries to the eye published to date. This kind of injury can be potentially sight-threatening, leading to severe visual loss in a small percentage of cases. We highlight the need for preventative measures such as labelling or devices to regulate cork pressure.}, } @article {pmid18695710, year = {2008}, author = {Nick, AM and Sood, AK}, title = {The ROC 'n' role of the multiplex assay for early detection of ovarian cancer.}, journal = {Nature clinical practice. Oncology}, volume = {5}, number = {10}, pages = {568-569}, doi = {10.1038/ncponc1214}, pmid = {18695710}, issn = {1743-4262}, abstract = {In order to overcome the significant mortality associated with ovarian cancer, a highly sensitive and specific screening test is urgently needed. CA125 is used to assess response to chemotherapy, detect recurrence, and distinguish malignant from benign disease; however, this marker is elevated in only 50-60% of stage I ovarian cancers, making it inadequate for early detection of malignancy. In this Practice Point, we discuss Visintin et al.'s attempt to validate a novel multiplex assay that uses a panel of six serum biomarkers -- leptin, prolactin, osteopontin, insulin-like growth factor II, macrophage inhibitory factor, and CA125. The study included 362 healthy controls and 156 patients with newly diagnosed ovarian cancer. The final model yielded 95.3% sensitivity, 99.4% specificity, a positive predictive value of 99.3% and a negative predictive value of 99.2%. These results indicate potential utility of this assay for early detection of ovarian cancer, although further validation is needed in a sample set representative of the general population.}, } @article {pmid18690361, year = {2008}, author = {Kulikowski, CA}, title = {Introducing Kuhn et al.'s paper "Informatics and medicine: from molecules to populations" and invited papers on this special topic.}, journal = {Methods of information in medicine}, volume = {47}, number = {4}, pages = {279-282}, pmid = {18690361}, issn = {0026-1270}, mesh = {Biomedical Research ; Education, Medical, Graduate ; Evidence-Based Medicine/*education ; *Medical Informatics ; Research/*education ; }, abstract = {OBJECTIVE: To introduce the paper by Kuhn et al. "Informatics and Medicine: From Molecules to Populations" and the papers that follow on this special topic in this issue of Methods of Information in Medicine, which opens a debate on the Kuhn et al. paper's assertions by an international panel of invited researchers in biomedical informatics.

METHOD: An introductory summary and comparative review of the Kuhn et al. paper and the debate papers, with some personal observations.

RESULTS: The Kuhn et al. paper makes a strong case for interdisciplinary education in biomedical informatics across institutions at the graduate level, which could be strengthened by analysis of previous relevant interdisciplinary experiences elsewhere, and the challenges they have faced, which point to more pervasive and earlier-stage needs for both education and practice bridging the research and healthcare communities.

CONCLUSIONS: The experts debating the Kuhn et al. paper strongly and broadly support the key recommendation of developing graduate education in biomedical informatics in a more comprehensive way, yet at the same time make some incisive comments about the limitations of the "positivistic" and excessively technological orientation of the paper, which could benefit from greater attention to the narrative and care-giving aspects of health practice, with more emphasis on its human and social aspects.}, } @article {pmid18678892, year = {2008}, author = {Carwardine, J and Wilson, KA and Ceballos, G and Ehrlich, PR and Naidoo, R and Iwamura, T and Hajkowicz, SA and Possingham, HP}, title = {Cost-effective priorities for global mammal conservation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {105}, number = {32}, pages = {11446-11450}, pmid = {18678892}, issn = {1091-6490}, mesh = {Agriculture/economics ; Animals ; *Biodiversity ; Cost Allocation ; Costs and Cost Analysis ; *Extinction, Biological ; *Mammals ; Resource Allocation/*economics ; }, abstract = {Global biodiversity priority setting underpins the strategic allocation of conservation funds. In identifying the first comprehensive set of global priority areas for mammals, Ceballos et al. [Ceballos G, Ehrlich PR, Soberón J, Salazar I, Fay JP (2005) Science 309:603-607] found much potential for conflict between conservation and agricultural human activity. This is not surprising because, like other global priority-setting approaches, they set priorities without socioeconomic objectives. Here we present a priority-setting framework that seeks to minimize the conflicts and opportunity costs of meeting conservation goals. We use it to derive a new set of priority areas for investment in mammal conservation based on (i) agricultural opportunity cost and biodiversity importance, (ii) current levels of international funding, and (iii) degree of threat. Our approach achieves the same biodiversity outcomes as Ceballos et al.'s while reducing the opportunity costs and conflicts with agricultural human activity by up to 50%. We uncover shortfalls in the allocation of conservation funds in many threatened priority areas, highlighting a global conservation challenge.}, } @article {pmid18670044, year = {2008}, author = {Mak, MW and Guo, J and Kung, SY}, title = {PairProSVM: protein subcellular localization based on local pairwise profile alignment and SVM.}, journal = {IEEE/ACM transactions on computational biology and bioinformatics}, volume = {5}, number = {3}, pages = {416-422}, doi = {10.1109/TCBB.2007.70256}, pmid = {18670044}, issn = {1557-9964}, mesh = {Algorithms ; Amino Acid Sequence ; Artificial Intelligence ; Molecular Sequence Data ; Pattern Recognition, Automated/*methods ; Proteins/*chemistry/*metabolism ; Sequence Alignment/*methods ; Sequence Analysis, Protein/*methods ; *Software ; Structure-Activity Relationship ; Subcellular Fractions/*metabolism ; Tissue Distribution ; }, abstract = {The subcellular locations of proteins are important functional annotations. An effective and reliable subcellular localization method is necessary for proteomics research. This paper introduces a new method---PairProSVM---to automatically predict the subcellular locations of proteins. The profiles of all protein sequences in the training set are constructed by PSI-BLAST and the pairwise profile-alignment scores are used to form feature vectors for training a support vector machine (SVM) classifier. It was found that PairProSVM outperforms the methods that are based on sequence alignment and amino-acid compositions even if most of the homologous sequences have been removed. This paper also demonstrates that the performance of PairProSVM is sensitive (and somewhat proportional) to the degree of its kernel matrix meeting the Mercer's condition. PairProSVM was evaluated on Reinhardt and Hubbard's, Huang and Li's, and Gardy et al.'s protein datasets. The overall accuracies on these three datasets reach 99.3\\%, 76.5\\%, and 91.9\\%, respectively, which are higher than or comparable to those obtained by sequence alignment and by the methods compared in this paper.}, } @article {pmid18667874, year = {2008}, author = {Sheps, SB}, title = {Measure for measure? The challenge of new thinking about patient safety.}, journal = {HealthcarePapers}, volume = {8}, number = {4}, pages = {62-7; discussion 69-75}, doi = {10.12927/hcpap.2008.19979}, pmid = {18667874}, issn = {1488-917X}, mesh = {Canada ; Hospital Administration/*standards ; *Hospital Mortality ; Humans ; Organizational Culture ; Palliative Care/organization & administration ; Quality Assurance, Health Care/organization & administration ; Quality Indicators, Health Care/*standards ; Reproducibility of Results ; Safety/*standards ; }, abstract = {Penfold and colleagues, in this issue of Healthcare Papers, provide a comprehensive and substantive critique of the hospital standardized mortality ratio (HSMR) as a measure of patient safety, and suggest a useful alternative. However, although measurement is not trivial, new thinking about patient safety presents a much greater challenge than just issues related to measurement. The measurement issue highlights the need for a re-conceptualization of what it takes, from a systems perspective, to achieve safety. This commentary first reviews Penfold et al.'s arguments (agreeing with their conclusions regarding the HSMR). It then presents some key elements of the new thinking about patient safety, particularly the emerging concepts of resilience and resonance, and notes how and why these are beginning to be applied in healthcare. Finally, it considers a number of reasons why a more comprehensive adoption of these new perspectives may be prolonged and notes that, while difficult, the journey is worth taking.}, } @article {pmid18665729, year = {2008}, author = {Burnham, BR and Neely, JH}, title = {A static color discontinuity can capture spatial attention when the target is an abrupt-onset singleton.}, journal = {Journal of experimental psychology. Human perception and performance}, volume = {34}, number = {4}, pages = {831-841}, doi = {10.1037/0096-1523.34.4.831}, pmid = {18665729}, issn = {0096-1523}, mesh = {*Attention ; *Color Perception ; Cues ; Discrimination Learning ; *Discrimination, Psychological ; Humans ; Intention ; Orientation ; Pattern Recognition, Visual ; Photic Stimulation ; Reaction Time ; *Space Perception ; }, abstract = {C. L. Folk, R. W. Remington, and J. C. Johnston's (1992) contingent involuntary orienting hypothesis states that a salient visual feature will involuntarily capture attention only when the observer's attentional set includes similar features. In four experiments, when the target's relevant feature was its being an abruptly onset singleton, attentional capture occurred for a static discontinuity cue that was the boundary between a group of red Xs contiguously joined to a group of green Os within a single row. Such an attentional capture effect is novel and contrary to Folk et al.'s (1992) hypothesis, because the attentional set for the target should have included abrupt onset but not color discontinuity, which was the feature that captured attention. These capture effects were involuntary because they occurred even when the target never appeared in the same location as the cue, and color could not have been used as a cue to signal the appearance of the target array (cf. B. S. Gibson & E. M. Kelsey, 1998).}, } @article {pmid18665140, year = {2008}, author = {Gersch, MS}, title = {Clopidogrel decreases arteriovenous fistula thrombosis but does not improve fistula maturation.}, journal = {Nature clinical practice. Nephrology}, volume = {4}, number = {9}, pages = {476-477}, doi = {10.1038/ncpneph0908}, pmid = {18665140}, issn = {1745-8331}, abstract = {This Practice Point commentary discusses Dember et al.'s randomized, double-blind, placebo-controlled trial of clopidogrel treatment after the creation of an arteriovenous fistula for dialysis. In total, 877 patients were treated with either placebo or clopidogrel (300 mg loading dose followed by 75 mg daily) for 6 weeks after fistula creation. Treatment with clopidogrel was associated with a significantly lower rate of fistula thrombosis than was placebo (12.2% vs 19.5%; P = 0.018). This reduction did not, however, lead to any changes in the secondary end point of attaining a useable access for dialysis; therefore, routine treatment with clopidogrel after fistula creation was not of clinical benefit in this well-conducted trial.}, } @article {pmid18648580, year = {2007}, author = {Bartlett, MR and Fink, RB and Schwartz, MF and Linebarger, M}, title = {Informativeness ratings of messages created on an AAC processing prosthesis.}, journal = {Aphasiology}, volume = {21}, number = {5}, pages = {475-498}, pmid = {18648580}, issn = {0268-7038}, support = {R01 HD043991/HD/NICHD NIH HHS/United States ; }, abstract = {BACKGROUND: SentenceShaper() (SSR) is a computer program that supports spoken language production in aphasia by recording and storing the fragments that the user speaks into the microphone, making them available for playback and allowing them to be combined and integrated into larger structures (i.e., sentences and narratives). A prior study that measured utterance length and grammatical complexity in story-plot narratives produced with and without the aid of SentenceShaper demonstrated an "aided effect" in some speakers with aphasia, meaning an advantage for the narratives that were produced with the support of this communication aid (Linebarger, Schwartz, Romania, Kohn, & Stephens, 2000). The present study deviated from Linebarger et al.'s methods in key respects and again showed aided effects of SentenceShaper in persons with aphasia. AIMS: Aims were (1) to demonstrate aided effects in "functional narratives" conveying hypothetical real-life situations from a first person perspective; (2) for the first time, to submit aided and spontaneous speech samples to listener judgements of informativeness; and (3) to produce preliminary evidence on topic-specific carryover from SentenceShaper, i.e., carryover from an aided production to a subsequent unaided production on the same topic. METHODS #ENTITYSTARTX00026; PROCEDURES: Five individuals with chronic aphasia created narratives on two topics, under three conditions: Unaided (U), Aided (SSR), and Post-SSR Unaided (Post-U). The 30 samples (5 participants, 2 topics, 3 conditions) were randomised and judged for informativeness by graduate students in speech-language pathology. The method for rating was Direct Magnitude Estimation (DME). OUTCOMES #ENTITYSTARTX00026; RESULTS: Repeated measures ANOVAs were performed on DME ratings for each participant on each topic. A main effect of Condition was present for four of the five participants, on one or both topics. Planned contrasts revealed that the aided effect (SSR >U) was significant in each of these cases. For two participants, there was also topic-specific carryover (Post-U >U). CONCLUSIONS: Listeners judged functional narratives generated on SentenceShaper to be more informative than comparable narratives spoken spontaneously. This extends the evidence for aided effects of SentenceShaper. There was also evidence, albeit weaker, for topic-specific carryover, suggesting that the program might be used effectively to practise for upcoming face-to-face interactions.}, } @article {pmid18636528, year = {2009}, author = {Guo, CY and Lunetta, KL and DeStefano, AL and Cupples, LA}, title = {Combined haplotype relative risk (CHRR): a general and simple genetic association test that combines trios and unrelated case-controls.}, journal = {Genetic epidemiology}, volume = {33}, number = {1}, pages = {54-62}, pmid = {18636528}, issn = {0741-0395}, support = {N01 HC025195/HC/NHLBI NIH HHS/United States ; N01 HC025195/HL/NHLBI NIH HHS/United States ; N01-HC-25195/HC/NHLBI NIH HHS/United States ; }, mesh = {Case-Control Studies ; Female ; Genome-Wide Association Study/*statistics & numerical data ; Haplotypes ; Humans ; Male ; Models, Genetic ; Models, Statistical ; Molecular Epidemiology ; Risk Factors ; }, abstract = {In some genetic association studies, samples contain both parental and unrelated controls. Under such scenarios, instead of analyzing only trios using family-based association tests or only unrelated subjects using a case-control study design, Nagelkerke et al. ([2004] Eur. J. Hum. Genet. 12:964-970) and Epstein et al. ([2005] Am. J. Hum. Genet. 76:592-608) proposed methods that implemented a likelihood ratio test to combine the two different types of data. In this article, we put forward a more powerful and simplified strategy to combine trios with unrelated subjects based on the haplotype relative risk (HRR) (Falk and Rubinstein [1987] Ann. Hum. Genet. 51:227-233). The HRR compares parental marker alleles transmitted to an affected offspring to those not transmitted as a test for association, a strategy that is similar to a case-control study that compares allele frequencies in diseased cases to those of unrelated controls. We prove that affected offspring can be pooled with diseased cases and that parental controls can be treated as unrelated controls when the trios and unrelated subjects are randomly sampled from the same population. Therefore, unrelated subjects can be incorporated into the HRR intuitively and effortlessly. For trios without complete parental genotypes, we adopted the strategy proposed by (Guo et al. [2005a] BMC Genet. 6:S90; [2005b] Hum. Hered. 59: 125-135), which is more feasible than the one proposed by Weinberg ([1999] Am. J. Hum. Genet. 64:1186-1193). In addition, simulation results suggest that the combined haplotype relative risk is more powerful than Epstein et al.'s method regardless of the disease prevalence in a homogeneous population.}, } @article {pmid18633800, year = {2006}, author = {Chakrabarti, B and Bullmore, E and Baron-Cohen, S}, title = {Empathizing with basic emotions: common and discrete neural substrates.}, journal = {Social neuroscience}, volume = {1}, number = {3-4}, pages = {364-384}, doi = {10.1080/17470910601041317}, pmid = {18633800}, issn = {1747-0927}, support = {G0600977/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Adult ; Brain/*physiology ; Brain Mapping/methods ; Emotions/*physiology ; *Empathy ; Facial Expression ; Female ; Humans ; Male ; Nerve Net/physiology ; Photic Stimulation/methods ; }, abstract = {Empathizing is a quantitative trait involving understanding another's mental state (including their emotion) and responding to this with an appropriate emotion. A reliable, behaviorally validated self-report questionnaire measure of this is the Empathy Quotient (EQ), which is continuously distributed across the general population. The "discrete emotions" model posits that each "basic" emotion has a relatively independent evolutionary antecedent and social-communicative function and is subserved by a discrete neural system. In this study, we investigate if and how empathy influences the perception of basic emotions. Twenty-five volunteers (13 female, 12 male) selected across EQ space participated in a correlational design 3T fMRI study. The stimuli were presented in a box-car design, where 5 blocks (each containing 4 video clips of any one of happy, sad, angry, disgust or neutral expressions from different actors) and a low-level baseline were presented in pseudo-random order. Using an exploratory analysis, we found different brain regions correlated with EQ, depending on which emotion was being perceived. In particular, the ventral striatal response to happy faces correlated positively with EQ, while the ventral striatal response to sad faces was negatively correlated with EQ. The precuneus and lateral prefrontal cortical response to angry faces correlated positively with EQ. The response of the insula and the superior temporal gyrus cortex to disgust faces were negatively correlated with EQ. These results are discussed in the light of the postulated evolutionary function of each emotion. Using a hypothesis-driven conjunction analysis, we found that a region in the left dorsal inferior frontal gyrus/premotor cortex was positively correlated to the EQ across all four emotions. This region could therefore constitute a biomarker for trait empathy across emotions. We conclude that there are common regions underlying empathy across different emotions, and there are regions that show an emotion-specific correlation with empathy. This pattern of results is interpreted using a modification of Haxby et al.'s model of face perception.}, } @article {pmid18628750, year = {2008}, author = {Gulyás, B and Nyáry, I and Borbély, K}, title = {FDG, MET or CHO? The quest for the optimal PET tracer for glioma imaging continues.}, journal = {Nature clinical practice. Neurology}, volume = {4}, number = {9}, pages = {470-471}, doi = {10.1038/ncpneuro0863}, pmid = {18628750}, issn = {1745-8358}, abstract = {This Practice Point commentary discusses a study by Kato et al. that assessed the usefulness of three PET tracers--(11)C-methionine (MET), (18)F-fluorodeoxyglucose, and (11)C-choline--for the metabolic evaluation of gliomas. The authors measured the ratio of tumor uptake to normal brain uptake (T/N ratio), with the frontal cortex as reference region, and analyzed the correlations between tracer uptake and tumor grade, type, and proliferation activity. Whereas all three tracers showed a similar correlation between the T/N ratio and tumor grade in astrocytic and oligodendroglial tumors, MET proved to be the most user-friendly marker in all gliomas as it enables the straightforward localization of 'hot lesions' and provides outstanding quantitative metabolic parameters. Here we highlight a few methodological issues arising from Kato et al.'s study and, consequently, we urge the PET community to reach a consensus on an objective approach towards the evaluation of PET tracers in the field of neuro-oncology.}, } @article {pmid18615347, year = {2009}, author = {Clarys, D and Bugaiska, A and Tapia, G and Baudouin, A}, title = {Ageing, remembering, and executive function.}, journal = {Memory (Hove, England)}, volume = {17}, number = {2}, pages = {158-168}, doi = {10.1080/09658210802188301}, pmid = {18615347}, issn = {1464-0686}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Aging/*physiology/psychology ; Analysis of Variance ; Humans ; Male ; Mental Recall/*physiology ; Middle Aged ; Neuropsychological Tests ; Pattern Recognition, Visual/physiology ; Reaction Time/*physiology ; Recognition, Psychology/*physiology ; Task Performance and Analysis ; Young Adult ; }, abstract = {This study was designed to investigate the relationship between executive functions and the age-related decline in episodic memory through the states-of-awareness approach. Following the presentation of a word list, a group of younger adults and a group of older adults undertook a recognition test in which they classified their responses according to the Remember-Know-Guess procedure (Gardiner & Richardson-Klavehn, 2000). In order to operationalise the executive function hypothesis, we investigated three specific executive functions (updating, shifting, and inhibition of a prepotent response) described in Miyake et al.'s (2000) theoretical model, and a complex executive task. The results revealed that fewer "R" responses were made during the recognition test by the older than the younger group, whereas there was no difference between the groups in the number of "K" responses. In addition, correlations indicated that remembering depended on executive function measures, whereas knowing did not. The hierarchical regression analyses showed that controlling for executive function, and particularly for the 2-back test, largely removed the age-related variance in remembering. These findings support the notion that executive dysfunction, and specifically updating decline, plays a central role in age-related memory loss.}, } @article {pmid18612328, year = {2008}, author = {Paulson, WD and White, JJ}, title = {Should arteriovenous fistulas and synthetic grafts undergo surveillance with pre-emptive correction of stenosis?.}, journal = {Nature clinical practice. Nephrology}, volume = {4}, number = {9}, pages = {480-481}, doi = {10.1038/ncpneph0878}, pmid = {18612328}, issn = {1745-8331}, abstract = {This Practice Point commentary discusses Tonelli et al.'s systematic review and meta-analysis of randomized controlled trials that evaluated surveillance of hemodialysis accesses. Tonelli et al. identified studies that used access blood-flow measurements or duplex ultrasound, and found only four publications of native fistulas and seven of synthetic grafts that met their criteria. Study quality was not high and statistical power was generally low. Tonelli et al. found that fistula surveillance reduced the risk of thrombosis without prolonging fistula life, and that graft surveillance showed no benefit. This commentary discusses why this small meta-analysis might have been biased towards not finding a benefit for stenosis surveillance of grafts by duplex ultrasound. Larger multicenter randomized trials are needed to establish the role of surveillance. Tonelli et al.'s study will encourage reconsideration of the current recommendation in clinical practice guidelines that grafts should undergo routine flow surveillance.}, } @article {pmid18609410, year = {2009}, author = {Kennedy, JS and Buehner, MJ and Rushton, SK}, title = {Adaptation to sensory-motor temporal misalignment: instrumental or perceptual learning?.}, journal = {Quarterly journal of experimental psychology (2006)}, volume = {62}, number = {3}, pages = {453-469}, doi = {10.1080/17470210801985235}, pmid = {18609410}, issn = {1747-0226}, mesh = {Adaptation, Psychological/*physiology ; Analysis of Variance ; Attention/physiology ; Feedback/physiology ; Humans ; Learning/*physiology ; Movement ; Photic Stimulation/methods ; Psychomotor Performance/*physiology ; Reaction Time/physiology ; Regression Analysis ; Reinforcement, Psychology ; Time Factors ; Visual Perception/*physiology ; }, abstract = {Sensory-motor delays vary over the course of development and under different environmental conditions. Previous research has shown that humans can compensate for the resulting temporal misalignment while performing sensory-motor tasks (e.g., Cunningham, Billock, & Tsou, 2001a), but remains silent on the question of whether perceptual learning-similar to that involved in adaptation to spatial misalignment (e.g., Redding & Wallace, 1993) and in adaptation to purely intersensory misalignment (e.g., Fujisaki, Shimojo, Kashino, & Nishida, 2004)-is also involved in this adaptive response. Following an attempted replication of Cunningham et al.'s (2001a) study in a preliminary experiment, we present in this paper two experiments that demonstrate that after-effects of adaptation to temporal misalignment do not spontaneously decay. The literature on adaptation to spatial misalignment suggests that, while instrumental learning spontaneously decays in the absence of reinforcement, perceptual learning persists. Therefore our results are consistent with adaptation being effected through perceptual learning.}, } @article {pmid18584446, year = {2008}, author = {Steele, RG and Van Allen, J and Benson, ER and Hunter, HL and McDermott, D}, title = {Associations between the repressive adaptive style and self-reported hope in Mexican American and Euro-American children.}, journal = {Journal of personality assessment}, volume = {90}, number = {4}, pages = {375-381}, doi = {10.1080/00223890802108071}, pmid = {18584446}, issn = {1532-7752}, mesh = {*Adaptation, Psychological ; *Affect ; Attitude/ethnology ; Child ; Female ; Hispanic or Latino/*psychology ; Humans ; Male ; Midwestern United States ; Psychology, Child ; *Repression, Psychology ; *Self Disclosure ; White People/*psychology ; }, abstract = {A large literature has examined the associations between Weinberger, Schwartz, and Davidson's (1979) repressive adaptive style (RAS) construct and various self-report measures of distress or unpleasant emotional states in adults and children. Fewer investigations have examined the role of RAS in self-reported positive psychology constructs. In this investigation, we used Weinberger et al.'s (1979) categorical typology to examine the associations between adaptive style and hope in Euro-American (n = 60) and Mexican American (n = 49) children (M age = 11.4 years) who were students at 1 of 3 parochial schools in a large Midwestern city. Partially supporting the hypotheses, a univariate 2 (ethnic group) x 2 (repressor group) analysis of variance indicated a significant main effect for adaptive style group but no significant main effect for ethnic group and no significant interaction effect. Results extend the literature on the associations between adaptive style and self-report instruments and indicate that (similar to self-reported measures of distress) self-reported hope may be subject to social desirability bias.}, } @article {pmid18573022, year = {2008}, author = {Thapar, A and Sniezek, SM}, title = {Aging and the revelation effect.}, journal = {Psychology and aging}, volume = {23}, number = {2}, pages = {473-477}, doi = {10.1037/0882-7974.23.2.473}, pmid = {18573022}, issn = {0882-7974}, support = {R01 AG17083-06/AG/NIA NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Aging/*psychology ; Attention ; Cues ; Female ; Humans ; *Illusions ; Imagination ; Judgment ; Male ; *Mental Recall ; Middle Aged ; Problem Solving ; *Repression, Psychology ; Semantics ; *Verbal Learning ; }, abstract = {Previous research by M. W. Prull, L. L. Light, M. E. Collett, and R. F. Kennison (1998) has shown that older adults are not susceptible to a memory illusion referred to as the revelation effect. The authors examined the robustness of Prull et al.'s findings by having participants solve a word fragment (Experiment 1) or an anagram (Experiment 2) prior to the recognition memory decision. In both experiments, younger and older adults showed a reliable revelation effect. These results simultaneously challenge both the conclusion that older adults are not vulnerable to the revelation effect and the conclusion that aging is associated with increasing susceptibility to memory illusions.}, } @article {pmid18572281, year = {2008}, author = {Mekinian, A and Lambert, M and Queyrel, V and Launay, D and Morell-Dubois, S and Hachulla, E and Mathurin, P and Hatron, PY}, title = {[Adult-onset Still's disease and hepatic angiosarcoma, a fortuitous association or a paraneoplastic syndrome: a case-report].}, journal = {La Revue de medecine interne}, volume = {29}, number = {11}, pages = {936-939}, doi = {10.1016/j.revmed.2008.01.028}, pmid = {18572281}, issn = {0248-8663}, mesh = {Adult ; Diagnosis, Differential ; Female ; Hemangiosarcoma/*pathology ; Humans ; Liver Neoplasms/*pathology ; Magnetic Resonance Imaging ; Paraneoplastic Syndromes/classification/*pathology ; Still's Disease, Adult-Onset/classification/*pathology ; }, abstract = {Adult-onset Still's disease is a systemic disorder without specific histological feature. Diagnosis requires to rule out any other disorder including neoplasia. Nevertheless, patients with paraneoplastic adult-onset Still's disease have been reported. We report a patient with an adult-onset Still's disease who presented with a liver involvement at onset. Two years later, a liver angiosarcoma was diagnosed. This report underlines the difficulty of the diagnosis of the adult-onset Still's disease even in the presence of Yamaguchi et al.'s [J Rheumatol 19 (1992) 424-30] and Fautrel et al.'s [Medicine 81 (2002) 194-200] classification criteria and may suggest a link between the initial clinical picture and the discovery nearly two years later, of a liver angiosarcoma.}, } @article {pmid18559138, year = {2009}, author = {Tse, CS and Altarriba, J}, title = {The word concreteness effect occurs for positive, but not negative, emotion words in immediate serial recall.}, journal = {British journal of psychology (London, England : 1953)}, volume = {100}, number = {Pt 1}, pages = {91-109}, doi = {10.1348/000712608X318617}, pmid = {18559138}, issn = {0007-1269}, mesh = {*Affect ; Humans ; *Mental Recall ; *Semantics ; Time Factors ; *Vocabulary ; }, abstract = {The present study examined the roles of word concreteness and word valence in the immediate serial recall task. Emotion words (e.g. happy) were used to investigate these effects. Participants completed study-test trials with seven-item study lists consisting of positive or negative words with either high or low concreteness (Experiments 1 and 2) and neutral (i.e. non-emotion) words with either high or low concreteness (Experiment 2). For neutral words, the typical word concreteness effect (concrete words are better recalled than abstract words) was replicated. For emotion words, the effect occurred for positive words, but not for negative words. While the word concreteness effect was stronger for neutral words than for negative words, it was not different for the neutral words and the positive words. We conclude that both word valence and word concreteness simultaneously contribute to the item and order retention of emotion words and discuss how Hulme et al.'s (1997) item redintegration account can be modified to explain these findings.}, } @article {pmid18523431, year = {2008}, author = {Rambod, M and Kovesdy, CP and Kalantar-Zadeh, K}, title = {Malnutrition-Inflammation Score for risk stratification of patients with CKD: is it the promised gold standard?.}, journal = {Nature clinical practice. Nephrology}, volume = {4}, number = {7}, pages = {354-355}, doi = {10.1038/ncpneph0834}, pmid = {18523431}, issn = {1745-8331}, abstract = {Traditional cardiovascular disease risk factors including hyperlipidemia and obesity are paradoxically associated with improved survival in individuals with advanced chronic kidney disease. Such paradoxes underscore the important role of malnutrition-inflammation-cachexia syndrome in chronic kidney disease mortality and highlight the urgent need for comprehensive but practical nutritional assessment tools. In this Practice Point commentary, Rambod and colleagues discuss a recent paper by Yamada et al. that used the Malnutrition-Inflammation Score (MIS) as the 'reference standard' to validate five simplified nutritional screening tools in 422 Japanese patients on hemodialysis. The study found the Geriatric Nutritional Risk Index to be the most accurate of the simplified tools for identifying those patients on dialysis who are at nutritional risk. The commentary authors discuss Yamada et al.'s study and conclude that although the MIS has been widely used in patients undergoing maintenance dialysis, its wide utility does not automatically make it the ultimate reference standard for assessing other nutritional scoring tools.}, } @article {pmid18521749, year = {2009}, author = {Schweigert, WA}, title = {The effects of multiple presentations on the ratings and memorability of novel figurative phrases.}, journal = {Journal of psycholinguistic research}, volume = {38}, number = {1}, pages = {25-42}, pmid = {18521749}, issn = {0090-6905}, mesh = {Analysis of Variance ; Humans ; *Mental Recall ; *Perception ; *Psycholinguistics ; Reading ; }, abstract = {How the perceptions of novel figurative phrases change over the course of numerous presentations were addressed in three studies using rating tasks (Studies 1 and 3) and recall tasks (Study 2). The present set of studies replicated much of Schweigert et al.'s (J Psychol Res 32:455-475, 2003) findings of changes in correlations among figurative phrases ratings. The results also suggest that catchiness, frequency heard agreement, and frequency used agreement can be used as predictors of phrase memorability and potential predictors of later idiomaticity.}, } @article {pmid18506171, year = {2008}, author = {Zand, MS}, title = {Safety and efficacy of influenza vaccination in renal transplant recipients.}, journal = {Nature clinical practice. Nephrology}, volume = {4}, number = {7}, pages = {358-359}, doi = {10.1038/ncpneph0830}, pmid = {18506171}, issn = {1745-8331}, support = {R01 AI098112/AI/NIAID NIH HHS/United States ; }, abstract = {This Practice Point commentary discusses Scharpé et al.'s single-center, nonrandomized, prospective trial of influenza vaccination in renal transplant recipients. In total, 165 transplant recipients and 41 healthy volunteers were vaccinated with a standard inactivated trivalent influenza vaccine (containing strains of the A/H1N1, A/H3N2 and B viruses). No rejection episodes or other adverse events were reported in either group. Influenza-specific antibody titers increased in renal transplant recipients following vaccination, as measured by comparison of pre-vaccination and post-vaccination seroprotection and seroresponse rates. This commentary discusses the limitations of the trial, and urges caution in extending the conclusions drawn by Scharpé et al. regarding the safety of the trivalent, non-adjuvant-containing influenza vaccine to newer adjuvant-assisted vaccines. Annual vaccination for influenza by use of the trivalent vaccine strategy without adjuvant should, however, be standard of care for all stable renal transplant recipients who do not have clinical contraindications.}, } @article {pmid18493237, year = {2008}, author = {Piraino, B and Bender, F}, title = {How should peritoneal-dialysis-associated peritonitis be treated?.}, journal = {Nature clinical practice. Nephrology}, volume = {4}, number = {7}, pages = {356-357}, doi = {10.1038/ncpneph0831}, pmid = {18493237}, issn = {1745-8331}, abstract = {In this Practice Point commentary, we discuss Wiggins et al.'s systematic review of the treatment of peritonitis, a serious problem in peritoneal dialysis patients. Wiggins and co-workers reported that most antibiotic classes were similarly effective for the treatment of peritonitis. Despite the limited data available, the investigators found that the intraperitoneal route was more effective than the intravenous route in preventing treatment failure, that intermittent dosing of various antibiotics was as effective as continuous administration of these drugs, and that glycopeptide-based regimens were more likely than first-generation cephalosporins to achieve a complete cure. Here, we discuss the importance of treating peritonitis and the lack of and limitations of existing data, and emphasize the urgent need for well-designed, large randomized trials in this area.}, } @article {pmid18489212, year = {2008}, author = {Chmielewski, M and Watson, D}, title = {The heterogeneous structure of schizotypal personality disorder: item-level factors of the Schizotypal Personality Questionnaire and their associations with obsessive-compulsive disorder symptoms, dissociative tendencies, and normal personality.}, journal = {Journal of abnormal psychology}, volume = {117}, number = {2}, pages = {364-376}, doi = {10.1037/0021-843X.117.2.364}, pmid = {18489212}, issn = {0021-843X}, mesh = {Adolescent ; Adult ; Diagnostic and Statistical Manual of Mental Disorders ; Dissociative Disorders/diagnosis/*psychology ; Factor Analysis, Statistical ; Female ; Humans ; Male ; Obsessive-Compulsive Disorder/diagnosis/*psychology ; Personality Inventory/*statistics & numerical data ; Psychometrics/statistics & numerical data ; Reference Values ; Reproducibility of Results ; Schizotypal Personality Disorder/diagnosis/*psychology ; Students/psychology ; }, abstract = {A. Raine et al.'s (1994) 3-factor scheme is currently the most widely accepted model of schizotypal personality disorder (SPD). Factor analytic studies of the Schizotypal Personality Questionnaire (SPQ; A. Raine, 1991) subscales, which represent the 9 Diagnostic and Statistical Manual of Mental Disorders (DSM) criteria for SPD, have provided the model's primary support. The use of only 9 modeled variables, however, limits the number of factors that can be extracted. To explicate this structure more fully, the authors conducted item-level factor analyses of the SPQ in a large student sample that completed the instrument twice within a 2-week interval. The authors' analyses failed to support either the 3-factor model of SPD or the 9 existing DSM-based subscales of the SPQ. Instead, 5 replicable dimensions emerged that capture recurrent symptom pairings found in the broader SPD literature: Social Anhedonia, Unusual Beliefs and Experiences, Social Anxiety, Mistrust, and Eccentricity/Oddity. These factors are only weakly correlated with each other and show differential correlational patterns with the Big Five personality traits, dissociative tendencies, and symptoms of obsessive-compulsive disorder. Moreover, they are congruent with dimensional models of personality psychopathology. Implications for SPD in DSM-V are discussed.}, } @article {pmid18484290, year = {2008}, author = {Schooler, C and Roberts, B and Cohen, R}, title = {Context, complexity, and cognitive processing in schizophrenia.}, journal = {Cognitive neuropsychiatry}, volume = {13}, number = {3}, pages = {250-266}, doi = {10.1080/13546800802058658}, pmid = {18484290}, issn = {1464-0619}, support = {//Intramural NIH HHS/United States ; }, mesh = {Adult ; Case-Control Studies ; *Cognition ; Female ; Humans ; Male ; *Motor Activity ; Saccades ; *Schizophrenic Psychology ; Task Performance and Analysis ; }, abstract = {BACKGROUND: Cohen et al.'s (1990, 1999) concept of context has been employed to explain various schizophrenic cognitive deficits. Braver et al.'s (2001) modified definition allows us to link context to cognitive complexity and explain a range of our experimental findings.

METHOD: Saccadic and manual responses to experimental paradigms involving familiar and unfamiliar versions of tasks varying in stimulus-response compatibility, response familiarity, and temporal factors were used. These include comparison of acoustic and visually driven saccades and antisaccades, manual and saccadic pattern reproduction, and colour (cognitively guided) saccades with two delay intervals.

RESULTS: In one experiment, schizophrenic participants, unlike controls, made fewer errors on the auditory compared to the visual antisaccade task, suggesting that prepotent responses are more easily inhibited when stimulus-response compatibility is reduced. In a second experiment in which a left-right response sequence is reproduced manually or saccadically, schizophrenic performance is impaired when the novel and thus more complex saccadic response is required. In the third experiment, a colour signal is interpreted to determine the correct direction of a saccade. With two different blocked delay intervals, shortening the delay results in schizophrenic performance decline, suggesting difficulty adjusting to temporal context changes.

CONCLUSION: These results, together with our previous findings (Schooler et al., 1997a; Zahn et al., 1998) suggest schizophrenic context processing deficits become increasingly evident as contexts become more complex. These results may be due to microgaps in schizophrenic individuals' maintenance of context.}, } @article {pmid18476476, year = {2008}, author = {Lorsbach, TC and Reimer, JF}, title = {Context processing and cognitive control in children and young adults.}, journal = {The Journal of genetic psychology}, volume = {169}, number = {1}, pages = {34-50}, doi = {10.3200/GNTP.169.1.34-50}, pmid = {18476476}, issn = {0022-1325}, mesh = {Adult ; Age Factors ; Attention/physiology ; Child ; Child Behavior/*physiology ; Cognition/*physiology ; Cues ; Form Perception/physiology ; Functional Laterality/physiology ; Humans ; Image Processing, Computer-Assisted ; Inhibition, Psychological ; Memory/physiology ; Models, Neurological ; Neuropsychological Tests/statistics & numerical data ; Prefrontal Cortex/*physiology ; Psychomotor Performance/physiology ; Reaction Time/physiology ; Signal Detection, Psychological/physiology ; }, abstract = {T. S. Braver and colleagues (e.g., T. S. Braver, J. D. Cohen, & D. M. Barch, 2002) have provided a theory of cognitive control that focuses on the role of context processing. According to their theory, an underlying context-processing mechanism is responsible for the cognitive control functions of attention, inhibition, and working memory. In the present study, the authors examined whether T. S. Braver et al.'s theory can account for developmental differences in cognitive control. The authors compared the performance of children (M age = 11.9 years, SD = 0.43 years) with that of young adults (M age = 21.7 years, SD = 3.61 years) on a continuous performance task (AX-CPT) that placed demands on context processing. The results suggest that developmental differences in the cognitive control functions of attention, inhibition, and working memory may be based on age-related changes in an underlying context-processing mechanism.}, } @article {pmid18462127, year = {2008}, author = {Marshall, CR}, title = {A simple method for bracketing absolute divergence times on molecular phylogenies using multiple fossil calibration points.}, journal = {The American naturalist}, volume = {171}, number = {6}, pages = {726-742}, doi = {10.1086/587523}, pmid = {18462127}, issn = {1537-5323}, mesh = {Animals ; *Fossils ; Genetic Speciation ; *Models, Genetic ; Paleontology ; *Phylogeny ; Turtles/*classification ; }, abstract = {A central challenge facing the temporal calibration of molecular phylogenies is finding a quantitative method for estimating maximum age constraints on lineage divergence times. Here, I provide such a method. This method requires an ultrametric tree generated without reference to the fossil record. Exploiting the fact that the relative branch lengths on the ultrametric tree are proportional to time, this method identifies the lineage with the greatest proportion of its true temporal range covered by the fossil record. The oldest fossil of this calibration lineage is used as the minimum age constraint. The maximum age constraint is obtained by adding a confidence interval onto the end point of the calibration lineage, thus making it possible to bracket the true divergence times of all lineages on the tree. The approach can also identify fossils that have been grossly misdated or misassigned to the phylogeny. The method assumes that the relative branch lengths on the ultrametric tree are accurate and that fossilization is random. The effect of violations of these assumptions is assessed. This method is simple to use and is illustrated with a reanalysis of Near et al.'s turtle data.}, } @article {pmid18459601, year = {2008}, author = {Rousseau, FL and Vallerand, RJ}, title = {An examination of the relationship between passion and subjective well-being in older adults.}, journal = {International journal of aging & human development}, volume = {66}, number = {3}, pages = {195-211}, doi = {10.2190/AG.66.3.b}, pmid = {18459601}, issn = {0091-4150}, mesh = {Aged ; Aged, 80 and over ; Female ; Humans ; *Leisure Activities ; Male ; Middle Aged ; *Motivation ; Quality of Life/*psychology ; Surveys and Questionnaires ; }, abstract = {Activity engagement has long been linked to improved subjective well-being (SWB) in old age. However, recent studies testing Vallerand et al.'s (2003) Dualistic Model of Passion suggest that the type of passionate activity that underlies activity engagement might influence the extent to which individuals benefit from an active lifestyle. In the present article we examined the relationship between harmonious and obsessive passionate activities and subjective well-being in older adults. Results showed that harmonious passion, through its influence on positive affect experienced during activity engagement, is associated with increases in SWB, whereas obsessive passion is associated with decreases in SWB. Engagement in passionate activities might be beneficial for older adults when a passionate activity is harmonious, but detrimental when a passionate activity is obsessive.}, } @article {pmid18454822, year = {2008}, author = {Sharp, TP}, title = {Job satisfaction among psychiatric registered nurses in New England.}, journal = {Journal of psychiatric and mental health nursing}, volume = {15}, number = {5}, pages = {374-378}, doi = {10.1111/j.1365-2850.2007.01239.x}, pmid = {18454822}, issn = {1365-2850}, mesh = {Adult ; Aged ; Female ; Humans ; *Job Satisfaction ; Male ; Middle Aged ; New England ; Nurses/*statistics & numerical data ; Psychiatric Nursing/*statistics & numerical data ; Surveys and Questionnaires ; }, abstract = {This research used Herzberg et al.'s two-factor theory as a framework with which to examine job satisfaction in a sample of 161 registered psychiatric nurses in the states of Connecticut, Maine and Massachusetts (USA). Weiss et al.'s Minnesota Satisfaction Questionnaire short form was used to measure possible relationships between ability utilization, compensation, co-workers, achievement and job satisfaction. Findings support Herzberg et al.'s theory, showing moderate correlations among nurses' ability utilization, achievement and job satisfaction. Mean general satisfaction of respondents was closer to satisfied than neutral; respondents indicated greatest satisfaction with ability utilization (86%) and achievement (83%); 67% were satisfied with co-workers, and 52% with compensation. Respondents were least satisfied with compensation, with 14% indicating that they were very dissatisfied. Although compensation was an issue, it is possible that other factors, such as safety, management conflict, and balancing the needs of job and family, if addressed, may help increase job satisfaction and retention of psychiatric nursing staff.}, } @article {pmid18444769, year = {2008}, author = {Taylor, KI and Salamoura, A and Randall, B and Moss, H and Tyler, LK}, title = {Clarifying the nature of the distinctiveness by domain interaction in conceptual structure: comment on Cree, McNorgan, and McRae (2006).}, journal = {Journal of experimental psychology. Learning, memory, and cognition}, volume = {34}, number = {3}, pages = {719-725}, doi = {10.1037/0278-7393.34.3.719}, pmid = {18444769}, issn = {0278-7393}, support = {G19/27/MRC_/Medical Research Council/United Kingdom ; }, mesh = {*Concept Formation ; Discrimination Learning ; Humans ; *Mental Recall ; *Pattern Recognition, Visual ; Psycholinguistics ; Reaction Time ; *Semantics ; Set, Psychology ; }, abstract = {The conceptual structure account of semantic memory (CSA; L. K. Tyler & H. E. Moss, 2001) claims that feature correlation (the degree to which features co-occur) and feature distinctiveness (the number of concepts in which a feature occurs) interact with domains of knowledge (e.g., living vs. nonliving) such that the distinctive features of nonliving things are more highly correlated than the distinctive features of living things. Evidence for (B. Randall, H. E. Moss, J. M. Rodd, M. Greer, & L. K. Tyler, 2004) and against this claim (G. S. Cree, C. McNorgan, & K. McRae, 2006) has been reported. This comment outlines the CSA, discusses Cree et al.'s (2006) critiques of the Randall et al. (2004) experiments and the CSA, and reports new analyses of property norm and behavioral data, which replicate the results reported by Randall et al. (2004).}, } @article {pmid18444055, year = {2008}, author = {Silverman, WK and Pina, AA and Viswesvaran, C}, title = {Evidence-based psychosocial treatments for phobic and anxiety disorders in children and adolescents.}, journal = {Journal of clinical child and adolescent psychology : the official journal for the Society of Clinical Child and Adolescent Psychology, American Psychological Association, Division 53}, volume = {37}, number = {1}, pages = {105-130}, doi = {10.1080/15374410701817907}, pmid = {18444055}, issn = {1537-4424}, support = {R01 63997//PHS HHS/United States ; }, mesh = {Adolescent ; Child ; Cognitive Behavioral Therapy/methods ; *Evidence-Based Medicine ; Family Therapy/methods ; Humans ; Phobic Disorders/diagnosis/*therapy ; Practice Guidelines as Topic ; Psychotherapy/*methods ; Psychotherapy, Group/methods ; }, abstract = {The article reviews psychosocial treatments for phobic and anxiety disorders in youth. Using criteria from Nathan and Gorman (2002), 32 studies are evaluated along a continuum of methodological rigor. In addition, the treatments evaluated in each of the 32 studies are classified according to Chambless et al.'s (1996) and Chambless and Hollon's (1998) criteria. Findings from a series of meta-analyses of the studies that used waitlists also are reported. In accordance with Nathan and Gorman, the majority of the studies were either methodologically robust or fairly rigorous. In accordance with Chambless and colleagues, although no treatment was well-established, Individual Cognitive Behavior Therapy, Group Cognitive Behavior Therapy (GCBT), GCBT with Parents, GCBT for social phobia (SOP), and Social Effectiveness Training for children with SOP each met criteria for probably efficacious. The other treatments were either possibly efficacious or experimental. Meta-analytic results revealed no significant differences between individual and group treatments on diagnostic recovery rates and anxiety symptom reductions, as well as other youth symptoms (i.e., fear, depression, internalizing and externalizing problems). Parental involvement was similarly efficacious as parental noninvolvement in individual and group treatment formats. The article also provides a summary of the studies that have investigated mediators, moderators, and predictors of treatment outcome. The article concludes with a discussion of the clinical representativeness and generalizability of treatments, practice guidelines, and future research directions.}, } @article {pmid18433014, year = {2008}, author = {Crowther, JH and Armey, M and Luce, KH and Dalton, GR and Leahey, T}, title = {The point prevalence of bulimic disorders from 1990 to 2004.}, journal = {The International journal of eating disorders}, volume = {41}, number = {6}, pages = {491-497}, doi = {10.1002/eat.20537}, pmid = {18433014}, issn = {1098-108X}, mesh = {Adult ; Bulimia Nervosa/diagnosis/*epidemiology/psychology ; Female ; Humans ; Incidence ; Prevalence ; Severity of Illness Index ; Surveys and Questionnaires ; }, abstract = {OBJECTIVE: This study investigated the point prevalence of probable cases of bulimia nervosa (BN), eating disorder not otherwise specified (EDNOS), and specific eating disorder symptomatology among 6,844 undergraduate women at a single site, examining changes across five 3-year time periods and on a yearly basis from 1990 to 2004.

METHOD: Participants completed a self-report checklist that assessed the diagnostic criteria for BN (American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders, 1994) and the Bulimia Test (Smith and Thelen, J Consult Clin Psychol, 52, 863-872, 1984) (BULIT) or Bulimia Test-Revised (Thelen et al., Psychol Assess, 3, 119-124, 1991) (BULIT-R).

RESULTS: Chi-square analyses comparing the percentages of probable cases of BN and EDNOS and the percentages of women who reported frequent binge eating and most compensatory weight control strategies were nonsignificant. Only the percentages of women who endorsed overconcern with weight and shape and diuretic use and excessive exercise as compensatory weight control strategies changed over time.

CONCLUSION: Consistent with Keel et al.'s (Keel et al., Psychol Med, 36, 119-127, 2006) findings regarding the point prevalence rates of BN from 1992 to 2002, results indicated that probable cases of eating disorders remained relatively stable. Methodologically, this research illustrates the importance of examining multiple data points when investigating stability or change in behavior.}, } @article {pmid18425127, year = {2008}, author = {Novembre, J and Stephens, M}, title = {Interpreting principal component analyses of spatial population genetic variation.}, journal = {Nature genetics}, volume = {40}, number = {5}, pages = {646-649}, pmid = {18425127}, issn = {1546-1718}, support = {R01 HG002585/HG/NHGRI NIH HHS/United States ; R01 HG02585-01/HG/NHGRI NIH HHS/United States ; }, mesh = {*Artifacts ; *Emigration and Immigration ; *Genetic Variation ; Humans ; Population/*genetics ; Principal Component Analysis/*standards ; }, abstract = {Nearly 30 years ago, Cavalli-Sforza et al. pioneered the use of principal component analysis (PCA) in population genetics and used PCA to produce maps summarizing human genetic variation across continental regions. They interpreted gradient and wave patterns in these maps as signatures of specific migration events. These interpretations have been controversial, but influential, and the use of PCA has become widespread in analysis of population genetics data. However, the behavior of PCA for genetic data showing continuous spatial variation, such as might exist within human continental groups, has been less well characterized. Here, we find that gradients and waves observed in Cavalli-Sforza et al.'s maps resemble sinusoidal mathematical artifacts that arise generally when PCA is applied to spatial data, implying that the patterns do not necessarily reflect specific migration events. Our findings aid interpretation of PCA results and suggest how PCA can help correct for continuous population structure in association studies.}, } @article {pmid18405322, year = {2008}, author = {Ballantyne, A}, title = {'Fair benefits' accounts of exploitation require a normative principle of fairness: response to Gbadegesin and Wendler, and Emanuel et al.}, journal = {Bioethics}, volume = {22}, number = {4}, pages = {239-244}, doi = {10.1111/j.1467-8519.2007.00622.x}, pmid = {18405322}, issn = {1467-8519}, mesh = {Biomedical Research/*ethics ; Community-Institutional Relations ; Ethics, Research ; Humans ; Internationality ; *Social Justice ; }, abstract = {In 2004 Emanuel et al. published an influential account of exploitation in international research, which has become known as the 'fair benefits account'. In this paper I argue that the thin definition of fairness presented by Emanuel et al, and subsequently endorsed by Gbadegesin and Wendler, does not provide a notion of fairness that is adequately robust to support a fair benefits account of exploitation. The authors present a procedural notion of fairness--the fair distribution of the benefits of research is to be determined on a case-by-case basis by the parties involved in each study. The fairness of the distribution of benefits is not assessed against an independent normative standard. Emanuel et al.'s account of fairness provides a framework for objecting only to transactions that occur without the fully informed consent of the weaker party. As a result, a debate about exploitation collapses into a debate about consent. This is problematic because, as the proponents of the fair benefits framework acknowledge, neither the trial participants' consent nor the host community's consent preclude exploitation. Attempts to stipulate normative standards of fairness to protect research subjects in developing countries have been controversial and divisive, and it is therefore understandable that bioethicists would be tempted to develop accounts of exploitation that are independent of such prescriptive principles. I conclude, however, that the utility of the fair benefits model of exploitation as a policy tool will ultimately depend on whether a substantive principle of fairness can be developed to underpin it.}, } @article {pmid18359030, year = {2008}, author = {Kurz, MJ and Judkins, TN and Arellano, C and Scott-Pandorf, M}, title = {A passive dynamic walking robot that has a deterministic nonlinear gait.}, journal = {Journal of biomechanics}, volume = {41}, number = {6}, pages = {1310-1316}, doi = {10.1016/j.jbiomech.2008.01.007}, pmid = {18359030}, issn = {0021-9290}, mesh = {Gait/*physiology ; Humans ; *Robotics ; Walking/*physiology ; }, abstract = {There is a growing body of evidence that the step-to-step variations present in human walking are related to the biomechanics of the locomotive system. However, we still have limited understanding of what biomechanical variables influence the observed nonlinear gait variations. It is necessary to develop reliable models that closely resemble the nonlinear gait dynamics in order to advance our knowledge in this scientific field. Previously, Goswami et al. [1998. A study of the passive gait of a compass-like biped robot: symmetry and chaos. International Journal of Robotic Research 17(12)] and Garcia et al. [1998. The simplest walking model: stability, complexity, and scaling. Journal of Biomechanical Engineering 120(2), 281-288] have demonstrated that passive dynamic walking computer models can exhibit a cascade of bifurcations in their gait pattern that lead to a deterministic nonlinear gait pattern. These computer models suggest that the intrinsic mechanical dynamics may be at least partially responsible for the deterministic nonlinear gait pattern; however, this has not been shown for a physical walking robot. Here we use the largest Laypunov exponent and a surrogation analysis method to confirm and extend Garcia et al.'s and Goswami et al.'s original results to a physical passive dynamic walking robot. Experimental outcomes from our walking robot further support the notion that the deterministic nonlinear step-to-step variations present in gait may be partly governed by the intrinsic mechanical dynamics of the locomotive system. Furthermore the nonlinear analysis techniques used in this investigation offer novel methods for quantifying the nature of the step-to-step variations found in human and robotic gait.}, } @article {pmid18349180, year = {2008}, author = {Rigouzzo, A and Girault, L and Louvet, N and Servin, F and De-Smet, T and Piat, V and Seeman, R and Murat, I and Constant, I}, title = {The relationship between bispectral index and propofol during target-controlled infusion anesthesia: a comparative study between children and young adults.}, journal = {Anesthesia and analgesia}, volume = {106}, number = {4}, pages = {1109-16, table of contents}, doi = {10.1213/ane.0b013e318164f388}, pmid = {18349180}, issn = {1526-7598}, mesh = {Adult ; Anesthesia Recovery Period ; Anesthesia, General/methods ; Anesthesia, Intravenous/*methods ; Anesthetics, Intravenous/*pharmacology ; Awareness ; Child ; Electroencephalography ; Humans ; Monitoring, Intraoperative/methods ; Piperidines/therapeutic use ; Propofol/*pharmacology ; Prospective Studies ; Remifentanil ; Treatment Outcome ; Wakefulness ; }, abstract = {BACKGROUND: In this prospective study, we compared the relationship between propofol concentrations and bispectral index (BIS) in children versus young adults anesthetized with target-controlled infusion (TCI) of propofol.

METHODS: Forty-five prepubertal subjects (children) and 45 postpubertal subjects (adults) were studied. All patients were anesthetized with TCI of propofol, based on the Kataria et al.'s model for children and on the Schnider et al.'s model for adults. All data from the BIS and the TCI system were continuously recorded using Rugloop software. Remifentanil was continuously administered throughout the study (0.25 microg x kg(-1) x min(-1)). In all patients, after the end of surgery, a 12-min period with a stable target plasma concentration (Ct) of propofol, randomly assigned at 2, 3, 4, 5, and 6 microg/mL, was performed. In addition, in most of the patients, another 12-min period was performed during which the BIS was targeted at 50 +/- 5. After each 12-min steady-state period, the Ct and BIS were noted and the plasma concentration of propofol was measured (Cm). The Ct and Cm corresponding to half maximal effect (BIS(50)) was determined by the Hill equation, and by targeting BIS at 50.

RESULTS: In children, as in adults, BIS values were highly correlated with the corresponding Ct or Cm of propofol following classical E(max) dose-response curves. The ECt(50) and the ECm(50), derived from the dose-response curves, were higher in children than in adults: ECm(50): 4.0 (3.6-4.5) microg/mL vs 3.3 (3.0-3.7) microg/mL [mean (95% CI)], P < 0.001; as well were the Ct and Cm clinically obtained when BIS was targeted at 50 (Cm(50): 4.3 +/- 1.1 microg/mL vs 3.4 +/- 1.2 microg/mL, (mean +/- SD) P < 0.05, children versus adults). Cm was generally under-estimated by the Ct, and the bias was higher in children than in adults: 2.6 +/- 2.6 microg/mL vs 1.7 +/- 1.6 microg/mL (P = 0.05).

CONCLUSIONS: The good relationship between propofol and BIS demonstrated in children as in adults suggested a slightly lower sensitivity to propofol in children. As the predictability of plasma propofol concentrations with the classical pharmacokinetic/pharmacodynamic models is limited in children, a cerebral pharmacodynamic feedback, such as BIS, may be useful in this population.}, } @article {pmid18338387, year = {2008}, author = {Szilágyi, A}, title = {A mathematically related singularity and the maximum size of protein domains.}, journal = {Proteins}, volume = {71}, number = {4}, pages = {2086-8; discussion 2089-90}, doi = {10.1002/prot.22000}, pmid = {18338387}, issn = {1097-0134}, mesh = {Amino Acid Sequence ; Models, Theoretical ; Molecular Sequence Data ; Protein Structure, Tertiary ; Proteins/*chemistry ; }, abstract = {In a paper titled "A topologically related singularity suggests a maximum preferred size for protein domains" (Zbilut et al., Proteins 2007;66:621-629), Zbilut et al. claim to have found a singularity in certain geometrical properties of protein structures, and suggest that this singularity may limit the maximum size of protein domains. They find further support for the singularity in their analysis of G-factors calculated by the PROCHECK program. Here, we show that the claimed singularity is a mathematical artifact with no physical meaning, and we reanalyze the G-factors to show that Zbilut et al.'s results are due to a single outlier in the data. Thus, the existence of an actual singularity in the topological properties of proteins is not supported by the findings of Zbilut et al.}, } @article {pmid18331244, year = {2008}, author = {Koenig, WD and Walters, EL}, title = {A tale of two worlds: molecular ecology and population structure of the threatened Florida scrub-jay.}, journal = {Molecular ecology}, volume = {17}, number = {7}, pages = {1632-1633}, doi = {10.1111/j.1365-294X.2008.03704.x}, pmid = {18331244}, issn = {1365-294X}, mesh = {Animals ; Conservation of Natural Resources ; *Demography ; Ecology ; Florida ; *Genetics, Population ; Passeriformes/*genetics ; }, abstract = {Elsewhere in this issue of Molecular Ecology, Coulon et al. provide a detailed analysis of population structure of the threatened Florida scrub-jay (Aphelocoma coerulescens) using genetic markers and compare it to that inferred from previous demographic surveys and observed dispersal behaviour in this species. In contrast to previous attempts at such comparisons, estimates from the two methods are reasonably congruent. Although challenges remain, Coulon et al.'s analyses demonstrate the potential for closing the gap between these alternative methodologies, and ultimately for future genetic surveys to be used confidently in conservation planning.}, } @article {pmid18318421, year = {2008}, author = {Arantes, J and Grace, RC}, title = {Failure to obtain value enhancement by within-trial contrast in simultaneous and successive discriminations.}, journal = {Learning & behavior}, volume = {36}, number = {1}, pages = {1-11}, pmid = {18318421}, issn = {1543-4494}, mesh = {Animals ; *Behavior, Animal ; Columbidae ; *Discrimination Learning ; }, abstract = {The present research tested the generality of the "work ethic" effect described by Clement, Feltus, Kaiser, and Zentall (2000). In Experiment 1, we trained 10 pigeons on a pair of either simultaneous or successive discriminations. One discrimination followed a high-effort requirement (20 pecks to the center key) and the other followed a low-effort requirement (1 peck). Contrary to Clement et al.'s results, we found that preferences between the S+ and S- stimuli in transfer tests depended on the event that initiated the trial: Pigeons preferred the stimulus from the baseline discrimination whose initiating event was most dissimilar from that preceding the test trial. Preferences were similar but less extreme in the successive condition. In Experiment 2, we investigated whether test preferences depended on the amount of training. A total of 12 pigeons were trained on a pair of simultaneous discriminations, except that test sessions were scheduled after every three baseline sessions. Preferences increased across test sessions but were similar to those in Experiment 1. Together with Vasconcelos, Urcuioli, and Lionello-DeNolf (2007a), our study represents a second failure to replicate Clement et al.'s work ethic effect. The finding that preference depends on the event that initiates the test trial suggests that choice probes may not provide unambiguous assessments of stimulus value.}, } @article {pmid18318411, year = {2008}, author = {Wilcox, RR and Tian, T}, title = {Comparing dependent correlations.}, journal = {The Journal of general psychology}, volume = {135}, number = {1}, pages = {105-112}, doi = {10.3200/GENP.135.1.105-112}, pmid = {18318411}, issn = {0022-1309}, mesh = {Bias ; *Data Interpretation, Statistical ; Humans ; Monte Carlo Method ; Psychology, Experimental/*standards ; Reproducibility of Results ; Research Design ; }, abstract = {In a recent article in The Journal of General Psychology, J. B. Hittner, K. May, and N. C. Silver (2003) described their investigation of several methods for comparing dependent correlations and found that all can be unsatisfactory, in terms of Type I errors, even with a sample size of 300. More precisely, when researchers test at the .05 level, the actual Type I error probability can exceed .10. The authors of this article extended J. B. Hittner et al.'s research by considering a variety of alternative methods. They found 3 that avoid inflating the Type I error rate above the nominal level. However, a Monte Carlo simulation demonstrated that when the underlying distribution of scores violated the assumption of normality, 2 of these methods had relatively low power and had actual Type I error rates well below the nominal level. The authors report comparisons with E. J. Williams' (1959) method.}, } @article {pmid18312339, year = {2008}, author = {Cosgrove, CL and Wood, MJ and Day, KP and Sheldon, BC}, title = {Seasonal variation in Plasmodium prevalence in a population of blue tits Cyanistes caeruleus.}, journal = {The Journal of animal ecology}, volume = {77}, number = {3}, pages = {540-548}, doi = {10.1111/j.1365-2656.2008.01370.x}, pmid = {18312339}, issn = {1365-2656}, mesh = {Age Factors ; Animals ; Biodiversity ; DNA Primers/chemistry ; Malaria, Avian/*epidemiology/parasitology ; Passeriformes/*parasitology ; Plasmodium/*isolation & purification ; Polymerase Chain Reaction/veterinary ; Prevalence ; *Seasons ; Time Factors ; }, abstract = {1. Seasonal variation in environmental conditions is ubiquitous and can affect the spread of infectious diseases. Understanding seasonal patterns of disease incidence can help to identify mechanisms, such as the demography of hosts and vectors, which influence parasite transmission dynamics. 2. We examined seasonal variation in Plasmodium infection in a blue tit Cyanistes caeruleus population over 3 years using sensitive molecular diagnostic techniques, in light of Beaudoin et al.'s (1971; Journal of Wildlife Diseases, 7, 5-13) model of seasonal variation in avian malaria prevalence in temperate areas. This model predicts a within-year bimodal pattern of spring and autumn peaks with a winter absence of infection. 3. Avian malaria infections were mostly Plasmodium (24.4%) with occasional Haemoproteus infections (0.8%). Statistical nonlinear smoothing techniques applied to longitudinal presence/absence data revealed marked temporal variation in Plasmodium prevalence, which apparently showed a within-year bimodal pattern similar to Beaudoin et al.'s model. However, of the two Plasmodium morphospecies accounting for most infections, only the seasonal pattern of Plasmodium circumflexum supported Beaudoin et al.'s model. On closer examination there was also considerable age structure in infection: Beaudoin et al.'s seasonal pattern was observed only in first year and not older birds. Plasmodium relictum prevalence was less seasonally variable. 4. For these two Plasmodium morphospecies, we reject Beaudoin et al.'s model as it does not survive closer scrutiny of the complexities of seasonal variation among Plasmodium morphospecies and host age classes. Studies of host-parasite interactions should consider seasonal variation whenever possible. We discuss the ecological and evolutionary implications of seasonal variation in disease prevalence.}, } @article {pmid18302682, year = {2008}, author = {Dlugosch, KM and Whitton, J}, title = {Can we stop transgenes from taking a walk on the wild side?.}, journal = {Molecular ecology}, volume = {17}, number = {5}, pages = {1167-1169}, doi = {10.1111/j.1365-294X.2008.03663.x}, pmid = {18302682}, issn = {1365-294X}, mesh = {Brassica napus/genetics ; Brassica rapa/genetics ; Herbicide Resistance/genetics ; Plants, Genetically Modified ; Transgenes/*genetics ; }, abstract = {Whether the potential costs associated with broad-scale use of genetically modified organisms (GMOs) outweigh possible benefits is highly contentious, including within the scientific community. Even among those generally in favour of commercialization of GM crops, there is nonetheless broad recognition that transgene escape into the wild should be minimized. But is it possible to achieve containment of engineered genetic elements in the context of large scale agricultural production? In a previous study, Warwick et al. (2003) documented transgene escape via gene flow from herbicide resistant (HR) canola (Brassica napus) into neighbouring weedy B. rapa populations (Fig. 1) in two agricultural fields in Quebec, Canada. In a follow-up study in this issue of Molecular Ecology, Warwick et al. (2008) show that the transgene has persisted and spread within the weedy population in the absence of selection for herbicide resistance. Certainly a trait like herbicide resistance is expected to spread when selected through the use of the herbicide, despite potentially negative epistatic effects on fitness. However, Warwick et al.'s findings suggest that direct selection favouring the transgene is not required for its persistence. So is there any hope of preventing transgene escape into the wild?}, } @article {pmid21730720, year = {2008}, author = {Zhang, WJ and Zhang, JY and Li, PJ and Shen, X and Zhang, QF and Wu, JL}, title = {The effects of contacts and ambipolar electrical transport in nitrogen doped multiwall carbon nanotubes.}, journal = {Nanotechnology}, volume = {19}, number = {8}, pages = {085202}, doi = {10.1088/0957-4484/19/8/085202}, pmid = {21730720}, issn = {0957-4484}, abstract = {The electrical transport properties of pristine single wall carbon nanotubes (SWCNTs) and lower nitrogen content doped multiwall carbon nanotubes (MWCNTs) (lower than in the experiments of Xiao et al (2005 J. Am. Chem. Soc. 127 8614)) in contact with Au and Pt were studied. Compared with pristine SWCNTs, the Fermi level of the lower nitrogen content doped MWCNTs also moved to the valence band edge with the contact metal's work function increasing. In contrast to Derycke et al' s results (2002 Appl. Phys. Lett. 80 2773), the lower nitrogen content doped MWCNTs exhibited ambipolar behavior, and increasing the doping level led to a reduction of the Schottky barrier height of electrons. Consistent with theoretical calculations, the results support the opinion that the degree of Fermi level pinning is minor for doped carbon nanotubes.}, } @article {pmid18293125, year = {2008}, author = {Wong, FY and Huang, ZJ and He, N and Smith, BD and Ding, Y and Fu, C and Young, D}, title = {HIV risks among gay- and non-gay-identified migrant money boys in Shanghai, China.}, journal = {AIDS care}, volume = {20}, number = {2}, pages = {170-180}, doi = {10.1080/09540120701534707}, pmid = {18293125}, issn = {0954-0121}, support = {R01 HD056956/HD/NICHD NIH HHS/United States ; R01 DA 15623-04S1/DA/NIDA NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; China/epidemiology ; Depressive Disorder/*psychology ; Epidemiologic Methods ; HIV Infections/epidemiology/prevention & control/*psychology ; Health Knowledge, Attitudes, Practice ; Homosexuality, Male/*psychology/statistics & numerical data ; Humans ; Male ; Sex Work/*statistics & numerical data ; Socioeconomic Factors ; Substance-Related Disorders/epidemiology/prevention & control/*psychology ; Transients and Migrants/psychology/*statistics & numerical data ; Urban Health ; }, abstract = {Men having sex with men (MSM) now account for 7% of all HIV/AIDS cases in China and there is growing awareness that internal rural-to-urban migration might shift the HIV epidemic within China by broadening social and sexual mixing. About 70% of HIV/AIDS infections are among rural residents, of whom 80% are males and 60% aged 16-29. This young, male, rural-to-urban migrant population has been identified as the 'tipping point' for the AIDS epidemic in China. A subgroup of these migrants is the 'money boy' population, i.e. those who engage in same-sex transactional sex for economic survival. However, the literature addressing money boys is very limited. The present study aims to elucidate factors for preventing substance abuse and HIV among two types of money boys 'gay-identified' and 'non-gay-identified' living in the Shanghai metropolitan area. This work is conceptually underpinned by Chng et al.'s (2003) tripartite model, which postulates that risk behaviors (e.g. substance abuse) engaged in by transient or non-native individuals are often shaped and regulated by factors in the home environment, migration experience and current environment. Results reveal gay and non-gay money boys were not significantly different in age, income, marriage status and education. Both groups shared similar patterns of substance use. Both groups had high self-reported depressive symptoms and low HIV knowledge. However, sexual orientation differentially predicted HIV testing, with gay money boys more likely to be tested for HIV. Non-gay money boys showed fewer sexual risks. HIV prevention targeting MSM (including money boys) within rapidly changing China is discussed, as are methodologies and outreach strategies most effective for particular subgroups of MSM.}, } @article {pmid18275423, year = {2008}, author = {Arshad, I}, title = {Response to Schönrock-Adema et al.'s paper on the assessment of professional behaviour in undergraduate medical education.}, journal = {Medical education}, volume = {42}, number = {3}, pages = {325; author reply 326}, doi = {10.1111/j.1365-2923.2008.03013.x}, pmid = {18275423}, issn = {1365-2923}, mesh = {Behavior ; Education, Medical, Undergraduate/*standards ; Professional Practice/*standards ; *Students, Medical ; }, } @article {pmid18267492, year = {1999}, author = {Chai, BB and Vass, J and Zhuang, X}, title = {Significance-linked connected component analysis for wavelet image coding.}, journal = {IEEE transactions on image processing : a publication of the IEEE Signal Processing Society}, volume = {8}, number = {6}, pages = {774-784}, doi = {10.1109/83.766856}, pmid = {18267492}, issn = {1057-7149}, abstract = {Recent success in wavelet image coding is mainly attributed to a recognition of the importance of data organization and representation. There have been several very competitive wavelet coders developed, namely, Shapiro's (1993) embedded zerotree wavelets (EZW), Servetto et al.'s (1995) morphological representation of wavelet data (MRWD), and Said and Pearlman's (see IEEE Trans. Circuits Syst. Video Technol., vol.6, p.245-50, 1996) set partitioning in hierarchical trees (SPIHT). We develop a novel wavelet image coder called significance-linked connected component analysis (SLCCA) of wavelet coefficients that extends MRWD by exploiting both within-subband clustering of significant coefficients and cross-subband dependency in significant fields. Extensive computer experiments on both natural and texture images show convincingly that the proposed SLCCA outperforms EZW, MRWD, and SPIHT. For example, for the Barbara image, at 0.25 b/pixel, SLCCA outperforms EZW, MRWD, and SPIHT by 1.41 dB, 0.32 dB, and 0.60 dB in PSNR, respectively. It is also observed that SLCCA works extremely well for images with a large portion of texture. For eight typical 256x256 grayscale texture images compressed at 0.40 b/pixel, SLCCA outperforms SPIHT by 0.16 dB-0.63 dB in PSNR. This performance is achieved without using any optimal bit allocation procedure. Thus both the encoding and decoding procedures are fast.}, } @article {pmid18266767, year = {2008}, author = {Wimpenny, P and Johnson, N and Walter, I and Wilkinson, JE}, title = {Tracing and identifying the impact of evidence-use of a modified pipeline model.}, journal = {Worldviews on evidence-based nursing}, volume = {5}, number = {1}, pages = {3-12}, doi = {10.1111/j.1741-6787.2007.00109.x}, pmid = {18266767}, issn = {1741-6787}, mesh = {Evidence-Based Medicine/*trends ; Humans ; *Models, Nursing ; Nursing Process/*trends ; }, abstract = {AIM: This paper opens up a discussion about effective ways of tracing and identifying impact of evidence implementation in the field of nursing, through the use of Nutley et al.'s concept of an impact continuum, and Glasziou's Pipeline Model.

APPROACH: Work to date on improving and evaluating the use of evidence in health care settings has tended to focus on evidence implementation as an endpoint or entity, often seen and measured in terms of change in practice. However, the direct application of evidence to practice is not straightforward. Glasziou's Pipeline Model of the different stages through which evidence flows, in the process of implementation, is critically reviewed in relation to five key issues: the type of evidence entering the pipeline; the linearity of the model; leakages and blockages in the pipeline; levels of impact; and impact measurement. The Pipeline Model is then combined with Nutley et al.'s continuum of impacts in order to present a Modified Pipeline Model.

DISCUSSION AND CONCLUSIONS: The Modified Pipeline Model enables evidence implementation to be viewed as a process rather than an entity in itself, which in turn enables longitudinal assessment of barriers and facilitators to evidence "flow." By flow we mean the way in which evidence is transferred from reporting or publication stages to patient outcomes. It also allows identification of the multiple impacts that can occur through the process of evidence implementation, which may be impact on the way the nurse thinks about practice to the healing rate of a leg ulcer. Finally, the Modified Model raises the issue of impacts beyond the pipeline, that is, those outcomes for patients that result from adherence to evidence-based care. This Modified Pipeline Model thus has the potential to support individuals and organizations in enhanced implementation planning, evaluation and management.}, } @article {pmid18249721, year = {2002}, author = {Barnard, K and Martin, L and Coath, A and Funt, B}, title = {A comparison of computational color constancy algorithms--part II: experiments with image data.}, journal = {IEEE transactions on image processing : a publication of the IEEE Signal Processing Society}, volume = {11}, number = {9}, pages = {985-996}, doi = {10.1109/TIP.2002.802529}, pmid = {18249721}, issn = {1057-7149}, abstract = {We test a number of the leading computational color constancy algorithms using a comprehensive set of images. These were of 33 different scenes under 11 different sources representative of common illumination conditions. The algorithms studied include two gray world methods, a version of the Retinex method, several variants of Forsyth's gamut-mapping method, Cardei et al.'s neural net method, and Finlayson et al.'s Color by Correlation method. We discuss a number of issues in applying color constancy ideas to image data, and study in depth the effect of different preprocessing strategies. We compare the performance of the algorithms on image data with their performance on synthesized data. All data used for this study are available online at http://www.cs.sfu.ca/(tilde)color/data, and implementations for most of the algorithms are also available (http://www.cs.sfu.ca/(tilde)color/code). Experiments with synthesized data (part one of this paper) suggested that the methods which emphasize the use of the input data statistics, specifically color by correlation and the neural net algorithm, are potentially the most effective at estimating the chromaticity of the scene illuminant. Unfortunately, we were unable to realize comparable performance on real images. Here exploiting pixel intensity proved to be more beneficial than exploiting the details of image chromaticity statistics, and the three-dimensional (3-D) gamut-mapping algorithms gave the best performance.}, } @article {pmid18249720, year = {2002}, author = {Barnard, K and Cardei, V and Funt, B}, title = {A comparison of computational color constancy algorithms--part I: methodology and experiments with synthesized data.}, journal = {IEEE transactions on image processing : a publication of the IEEE Signal Processing Society}, volume = {11}, number = {9}, pages = {972-983}, doi = {10.1109/TIP.2002.802531}, pmid = {18249720}, issn = {1057-7149}, abstract = {We introduce a context for testing computational color constancy, specify our approach to the implementation of a number of the leading algorithms, and report the results of three experiments using synthesized data. Experiments using synthesized data are important because the ground truth is known, possible confounds due to camera characterization and pre-processing are absent, and various factors affecting color constancy can be efficiently investigated because they can be manipulated individually and precisely. The algorithms chosen for close study include two gray world methods, a limiting case of a version of the Retinex method, a number of variants of Forsyth's gamut-mapping method, Cardei et al.'s neural net method, and Finlayson et al.'s color by correlation method. We investigate the ability of these algorithms to make estimates of three different color constancy quantities: the chromaticity of the scene illuminant, the overall magnitude of that illuminant, and a corrected, illumination invariant, image. We consider algorithm performance as a function of the number of surfaces in scenes generated from reflectance spectra, the relative effect on the algorithms of added specularities, and the effect of subsequent clipping of the data. All data is available on-line at http://www.cs.sfu.ca/(tilde)color/data, and implementations for most of the algorithms are also available (http://www.cs.sfu.ca/(tilde)color/code).}, } @article {pmid18243937, year = {2008}, author = {Dobkin, PL}, title = {Mindfulness-based stress reduction: what processes are at work?.}, journal = {Complementary therapies in clinical practice}, volume = {14}, number = {1}, pages = {8-16}, doi = {10.1016/j.ctcp.2007.09.004}, pmid = {18243937}, issn = {1744-3881}, mesh = {Adult ; Aged ; Breast Neoplasms/complications/*psychology/therapy ; Depression/etiology/*prevention & control ; Female ; Focus Groups ; Humans ; *Mental Healing ; Middle Aged ; Psychological Theory ; Qualitative Research ; Self Care ; Stress, Psychological/complications/*prevention & control/*psychology ; Treatment Outcome ; }, abstract = {Mindfulness-Based Stress Reduction (MBSR) is a program that has been shown to be beneficial for clinical and non-clinical populations. While much attention has been paid to participants' outcomes, little work has been published concerning processes underlying improvements. Herein, women who had finished medical treatment for breast cancer completed questionnaires pre- and post-MBSR and were interviewed using focus group methodology such that quantitative and qualitative data were combined to explore potential mechanisms underlying changes. It was found that the Mindfulness Attention Awareness Scale was a useful process measure to assess changes in mindfulness and that the Coping with Health Injuries and Problems questionnaire was useful in documenting changes in palliative (self-care) coping over the course of the 8 week program. Moreover, the Sense of Coherence questionnaire suggested that the women viewed life as more meaningful and manageable following MSBR. Our findings fit with Shapiro et al.'s theory that, over time, participants in an MBSR program "reperceive" what they encounter in their daily experiences.}, } @article {pmid18241509, year = {2004}, author = {Branigan, HP and Pickering, MJ}, title = {Syntactic representation in the lemma stratum.}, journal = {The Behavioral and brain sciences}, volume = {27}, number = {2}, pages = {296-297}, doi = {10.1017/S0140525X04250075}, pmid = {18241509}, issn = {1469-1825}, abstract = {Levelt, Roelofs, & Meyer (henceforth Levelt et al. 1999) propose a model of production incorporating a lemma stratum, which is concerned with the syntactic characteristics of lexical entries. We suggest that syntactic priming experiments provide evidence about how such syntactic information is represented, and that this evidence can be used to extend Levelt et al.'s model. Evidence from syntactic priming experiments also supports Levelt et al.'s conjecture that the lemma stratum is shared between the production and comprehension systems.}, } @article {pmid18241446, year = {2003}, author = {Call, J}, title = {On linking comparative metacognition and theory of mind.}, journal = {The Behavioral and brain sciences}, volume = {26}, number = {3}, pages = {341-342}, doi = {10.1017/S0140525X03230089}, pmid = {18241446}, issn = {1469-1825}, abstract = {Smith et al.'s article provides a convincing argument for devoting increased research attention to comparative metacognition. However, this increased attention should be complemented with establishing links with comparative theory of mind (ToM) research, which are currently missing. I present a task in which pairs of subjects are presented with incomplete information in an object-choice situation that could be used to establish that link.}, } @article {pmid18241422, year = {2001}, author = {Dawson, MR}, title = {Feature development, object concepts, and the scope slip.}, journal = {The Behavioral and brain sciences}, volume = {24}, number = {6}, pages = {1146-1147}, doi = {10.1017/S0140525X01280145}, pmid = {18241422}, issn = {1469-1825}, abstract = {Schyns et al.'s (1998) target article raises a conflict between the need for a fixed functional architecture in an explanatory cognitive science and the need for a system to learn to detect new features. This conflict can be resolved by avoiding the scope slip in which properties of objects are erroneously viewed as being properties of their representations.}, } @article {pmid18234791, year = {2008}, author = {Worobey, M}, title = {Phylogenetic evidence against evolutionary stasis and natural abiotic reservoirs of influenza A virus.}, journal = {Journal of virology}, volume = {82}, number = {7}, pages = {3769-3774}, pmid = {18234791}, issn = {1098-5514}, support = {R21 AI065371/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Disease Reservoirs/*virology ; Humans ; Influenza A virus/*genetics ; Phylogeny ; RNA, Viral/*genetics ; Sequence Analysis, DNA ; Siberia ; Water Microbiology ; }, abstract = {Zhang et al. (G. Zhang, D. Shoham, D. Gilichinsky, S. Davydov, J. D. Castello, and S. O. Rogers, J. Virol. 80:12229-12235, 2006) have claimed to have recovered influenza A virus RNA from Siberian lake ice, postulating that ice might represent an important abiotic reservoir for the persistence and reemergence of this medically important pathogen. A rigorous phylogenetic analysis of these influenza A virus hemagglutinin gene sequences, however, indicates that they originated from a laboratory reference strain derived from the earliest human influenza A virus isolate, WS/33. Contrary to Zhang et al.'s assertions that the Siberian "ice viruses" are most closely related either to avian influenza virus or to human influenza virus strains from Asia from the 1960s (Zhang et al., J. Virol. 81:2538 [erratum], 2007), they are clearly contaminants from the WS/33 positive control used in their laboratory. There is thus no credible evidence that environmental ice acts as a biologically relevant reservoir for influenza viruses. Several additional cases with findings that seem at odds with the biology of influenza virus, including modern-looking avian influenza virus RNA sequences from an archival goose specimen collected in 1917 (T. G. Fanning, R. D. Slemons, A. H. Reid, T. A. Janczewski, J. Dean, and J. K. Taubenberger, J. Virol. 76:7860-7862, 2002), can also be explained by laboratory contamination or other experimental errors. Many putative examples of evolutionary stasis in influenza A virus appear to be due to laboratory artifacts.}, } @article {pmid18230817, year = {2008}, author = {Meline, T and Harn, WE}, title = {Comments on Bothe, Davidow, Bramlett, Franic, and Ingham (2006).}, journal = {American journal of speech-language pathology}, volume = {17}, number = {1}, pages = {93-7; author reply 98-101}, doi = {10.1044/1058-0360(2008/009)}, pmid = {18230817}, issn = {1058-0360}, mesh = {Benzodiazepines/therapeutic use ; Drug Therapy/*methods ; Humans ; Olanzapine ; *Professional Competence ; Selective Serotonin Reuptake Inhibitors/therapeutic use ; Stuttering/*drug therapy ; }, abstract = {PURPOSE: To critically assess the quality, methodology, and conclusions in A. K. Bothe, J. H. Davidow, R. E. Bramlett, D. M. Franic, and R. J. Ingham's (2006) systematic review of pharmacological approaches to stuttering.

METHOD: A. D. Oxman and G. H. Guyatt's (1988) guidelines for reading literature reviews and A. D. Oxman and G. H. Guyatt's (1991) criteria for assessing the scientific quality of systematic reviews were adopted to accomplish the purpose.

RESULTS: Bothe et al.'s review was rated on a 7-point scale from extensive flaws on the high end to minimal flaws on the low end of the scale. The ratings varied from poor to good.

CONCLUSIONS: We judged Bothe et al.'s review of the pharmacological literature as it pertains to stuttering as flawed in its methodology and conclusions. However, we agree that the existing evidence for the use of pharmacological agents with persons who stutter is insufficient to recommend them in practice. Directions for improving the quality of clinical trials are suggested. In addition, we advocate for the multimethod measurement in stuttering research, including comparison, subjective evaluation, and social impact measures.}, } @article {pmid18203980, year = {2008}, author = {Sánchez, JP and Misztal, I and Bertrand, JK}, title = {Evaluation of methods for computing approximate accuracies of predicted breeding values in maternal random regression models for growth traits in beef cattle.}, journal = {Journal of animal science}, volume = {86}, number = {5}, pages = {1057-1066}, doi = {10.2527/jas.2007-0398}, pmid = {18203980}, issn = {1525-3163}, mesh = {Age Factors ; Animals ; Breeding/*statistics & numerical data ; Cattle/*genetics/*growth & development ; Cluster Analysis ; Computer Simulation ; Crosses, Genetic ; Female ; Genetics, Population ; Linear Models ; Male ; *Models, Genetic ; Observer Variation ; Predictive Value of Tests ; Regression Analysis ; Reproducibility of Results ; Sensitivity and Specificity ; Sex Factors ; }, abstract = {The objective of this study was to determine the suitability of 2 methods for computing approximate accuracies of predicted breeding values, in which accuracy was defined as the squared correlation between the predicted and true breeding value, when modeling growth traits in beef cattle using random regression (RR) models. The first method (Strabel et al., S-M-B) was designed for use with multitrait models; thus, its use with RR models requires the clustering of measurements into different traits. The second method (Tier and Meyer, T-M) was more general, because it accounted for random coefficients other than zeros and ones and thus it could be used directly when fitting RR models. To investigate the performance of both methods, their results were compared with the true accuracies using a balanced simulated data set. The largest difference between approximate and true average accuracies for direct effects was observed at 205 d when S-M-B was used (4.6% males and 8.8% females). With regard to maternal effects, the largest differences in average accuracies were observed at 205 d in males when S-M-B was used (31.8%) and at the same age in females but when using T-M (33.3%). In general, bias increased for direct effect accuracies in males at the tails of the accuracy range, but for females and for maternal effect accuracies in both sexes, bias increased as accuracy increased. When a population was simulated to create large numbers of progeny for base females that did not have individual records, much greater errors were observed in the regression of approximate values on the true ones. When both approximate methods were compared using a real beef cattle data set, a good agreement was observed, particularly for direct effect accuracies in sires [i.e., at 205 d, the regressions were 0.98 (direct) and 0.95 (maternal) with r(2) over 0.99]. The largest discrepancies for sires between the methods were observed at 205 d for direct (2.7%) and maternal (16.3%) effect accuracies. For dams, the largest differences between methods were also observed at 205 d, 9.3% (direct), and 15.2% (maternal). The differences between methods for nonparent cattle were greater than for dams for maternal effect accuracies but intermediate between sires and dams for direct effect accuracies. In spite of the less biased results provided by T-M, its use could be problematic when employed in evaluations of large populations due to its greater memory and computation requirements (e.g., 170 and 478% more than S-M-B for a population of 11 million).}, } @article {pmid18177886, year = {2008}, author = {Chibowski, E and Terpilowski, K}, title = {Surface free energy of sulfur--revisited I. Yellow and orange samples solidified against glass surface.}, journal = {Journal of colloid and interface science}, volume = {319}, number = {2}, pages = {505-513}, doi = {10.1016/j.jcis.2007.10.059}, pmid = {18177886}, issn = {0021-9797}, abstract = {Surface free energy of two different samples of solidified sulfur (yellow and orange) was investigated, using several approaches for its determination. It was found that values determined about two decades ago for surface free energy of sulfur were overestimated. From current studies the apparent value of this energy ranges between 30 and 60 mJ/m(2), depending on the kind and age of the sulfur samples (up to 1 year old) and/or the probe liquid used for the advancing and receding contact angle measurements. The energy has been calculated from van Oss et al.'s approach (Lifshitz-van der Walls, electron-donor, and electron-acceptor components), the contact angle hysteresis approach proposed by Chibowski, the equation of Owens and Wendt (dispersion and polar components), and Neumann et al.'s equation of state, as well as from equilibrium contact angle using Tadmor's procedure. The lowest values of the energy for 3-day- and 3-month-old samples of sulfur were calculated from the equation of state; they were below the range mentioned above.}, } @article {pmid18172235, year = {2008}, author = {Licari, FW and Knight, GW and Guenzel, PJ}, title = {Designing evaluation forms to facilitate student learning.}, journal = {Journal of dental education}, volume = {72}, number = {1}, pages = {48-58}, pmid = {18172235}, issn = {0022-0337}, mesh = {*Clinical Competence ; Education, Dental/*methods ; Educational Measurement/*methods ; Faculty, Dental ; Humans ; Program Evaluation/*methods ; Reproducibility of Results ; Students, Dental ; Surveys and Questionnaires/*standards ; United States ; }, abstract = {Most dental school instructors struggle to develop course evaluation criteria that can effectively be applied as valid and reliable learning instruments. Vague and unreliable learning assessments often lead to increased dissatisfaction among both faculty and students. Students complain about the "lack of faculty calibration," and faculty are often unable to adequately evaluate competence due to the need to provide an overall course grade by the end of the term. By systematically addressing Mackenzie et al.'s list of sixteen factors that contribute to faculty disagreements on student evaluation, we developed "Criteria for Writing Effective Evaluation Forms" as a guide for developing evaluation criteria. By using the guide for developing evaluation forms for student learning, course directors will have the components necessary to ensure validity and reliability of student assessment methodology. By providing students and faculty with clearly defined criteria and the training to apply those criteria, Mackenzie et al.'s concerns may be conquered.}, } @article {pmid18172233, year = {2008}, author = {Maillet, JP and Millar, AM and Burke, JM and Maillet, MA and Maillet, WA and Neish, NR}, title = {Effect of magnification loupes on dental hygiene student posture.}, journal = {Journal of dental education}, volume = {72}, number = {1}, pages = {33-44}, pmid = {18172233}, issn = {0022-0337}, mesh = {Canada ; *Dental Hygienists/education ; Education, Dental/methods ; Ergonomics ; Humans ; *Lenses ; Linear Models ; Musculoskeletal Diseases/*prevention & control ; Occupational Diseases/*prevention & control ; Optics and Photonics ; *Posture ; }, abstract = {The chair-side work posture of dental hygienists has long been a concern because of health-related problems potentially caused or exacerbated by poor posture. The purpose of this study was to investigate if using magnification loupes improved dental hygiene students' posture during provision of treatment. The treatment chosen was hand-scaling, and the effect of the timing of introduction of the loupes to students was also examined. Thirty-five novice dental hygiene students took part in the study. Each student was assessed providing dental hygiene care with and without loupes, thus controlling for innate differences in natural posture. Students were randomized into two groups. Group one used loupes in the first session and did not use them for the second session. Group two reversed this sequence. At the end of each session, all students were videotaped while performing scaling procedures. Their posture was assessed using an adapted version of Branson et al.'s Posture Assessment Instrument (PAI). Four raters assessed students at three time periods for nine posture components on the PAI. A paired t-test compared scores with and without loupes for each student. Scores showed a significant improvement in posture when using loupes (p<0.0001), and these improvements were significantly more pronounced for students starting loupes immediately on entering the program compared with students who delayed until the second session (p<0.1). These results suggest a significant postural benefit is realized by requiring students to master the use of magnification loupes as early as possible within the curriculum.}, } @article {pmid18171388, year = {2008}, author = {Wilson, DS}, title = {Social semantics: toward a genuine pluralism in the study of social behaviour.}, journal = {Journal of evolutionary biology}, volume = {21}, number = {1}, pages = {368-373}, doi = {10.1111/j.1420-9101.2007.01396.x}, pmid = {18171388}, issn = {1420-9101}, mesh = {Animals ; *Biological Evolution ; *Social Behavior ; *Terminology as Topic ; }, abstract = {Pluralism is the coexistence of equivalent theoretical frameworks, either because they are historically entrenched or because they achieve separate insights by viewing the same process in different ways. A recent article by West et al. [Journal of Evolutionary Biology (2007) vol. 20, 415-432] attempts to classify the many equivalent frameworks that have been developed to study the evolution of social behaviour. This article addresses shortcomings in the West et al.'s article, especially with respect to multilevel selection, in a common effort to maximize the benefits of pluralism while minimizing the semantic costs.}, } @article {pmid20078017, year = {2008}, author = {Dellefield, ME}, title = {The work of the RN Minimum Data Set coordinator in its organizational context.}, journal = {Research in gerontological nursing}, volume = {1}, number = {1}, pages = {42-51}, doi = {10.3928/19404921-20080101-04}, pmid = {20078017}, issn = {1940-4921}, mesh = {Adult ; Aged ; *Attitude of Health Personnel ; Certification/organization & administration ; Data Collection/*methods ; Female ; Focus Groups ; Geriatric Assessment/*methods ; Geriatric Nursing/organization & administration ; Humans ; Mandatory Programs/organization & administration ; Medicaid/organization & administration ; Medicare/organization & administration ; Middle Aged ; *Nurse's Role ; Nursing Assessment/*organization & administration ; *Nursing Homes/organization & administration ; Nursing Methodology Research ; Patient Admission ; Patient Care Planning/organization & administration ; Pilot Projects ; Qualitative Research ; Surveys and Questionnaires ; Total Quality Management/organization & administration ; United States ; }, abstract = {The Resident Assessment Instrument/Minimum Data Set (RAI/MDS) is the foundational clinical framework for nursing home care, functioning as both a clinical assessment instrument and an assessment process. An RN is mandated by statute to complete or coordinate the work associated with this framework. Using both focus groups and questionnaires, 24 RN MDS coordinators attending a national conference for MDS coordinators described their work in its organizational context. Shortell et al.'s continuous quality framework of structural, technical, cultural, and strategic organizational dimensions was used to categorize descriptive themes. Clinical implications of the study findings are summarized.}, } @article {pmid19287163, year = {2008}, author = {Nozawa, M and Nei, M}, title = {Genomic drift and copy number variation of chemosensory receptor genes in humans and mice.}, journal = {Cytogenetic and genome research}, volume = {123}, number = {1-4}, pages = {263-269}, pmid = {19287163}, issn = {1424-859X}, support = {R01 GM020293/GM/NIGMS NIH HHS/United States ; GM020293/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Gene Dosage/*genetics ; Genome/*genetics ; Humans ; Mice ; Receptors, G-Protein-Coupled/*genetics ; Receptors, Odorant/*genetics ; Sensation/*genetics ; Vomeronasal Organ/metabolism ; }, abstract = {Recent studies about the structural variation of genomic sequences have shown that there is a large amount of copy number variations (CNVs) of genes within species. Analyzing Redon et al.'s (2006) crude data on copy number variable regions (CNVRs), we previously showed that CNVs are particularly high for chemosensory receptor genes in human populations. In this paper, we reanalyzed the CNVs of these genes using more refined data by Perry et al. (2008). The results showed that the extent of CNVs is somewhat lower in this dataset than in the previous one, but that the extent is still substantial for olfactory receptor (OR), vomeronasal receptor (VR), and taste receptor (TR) genes. We also studied the CNVs for chemosensory receptor genes in mice, using CNVR data obtained from inbred strains. It was found that the extent of CNVs is quite substantial but is lower than that for human populations. However, because the mouse data came from inbred strains and might be biased, this conclusion should be regarded as tentative. Despite this reservation, the distribution of gene copy number for the OR gene family was approximately normal in both humans and mice, suggesting that genomic drift caused by random duplication and deletion of genes plays important roles in determining the evolutionary change of chemosensation.}, } @article {pmid18080959, year = {2007}, author = {Curran, VR and Sharpe, D}, title = {A framework for integrating interprofessional education curriculum in the health sciences.}, journal = {Education for health (Abingdon, England)}, volume = {20}, number = {3}, pages = {93}, pmid = {18080959}, issn = {1469-5804}, mesh = {*Curriculum ; Education, Professional/methods ; Health Occupations/*education ; Humans ; *Interprofessional Relations ; *Models, Educational ; Problem-Based Learning/methods ; }, abstract = {CONTEXT: Traditionally, the structures of health professional education in Canada and elsewhere have been largely based on "silos" in which health professionals are educated in relative isolation to one another. The curriculum content and structure has followed strict disciplinary lines. Recent commissions, committees and policy documents in Canada have identified the importance of reshaping educational preparation and the professional training of health care professionals (Commission on the Future of Health Care in Canada, 2002; Health Council of Canada, 2005).

OBJECTIVES: This brief communication describes an interprofessional curricular approach that combines characteristics of Barr et al.'s (2005) extracurricular and crossbar models of interprofessional education curriculum.

METHODS: An interprofessional education curriculum that combines principles of an integrative, continuous, early-to-late and blended learning approach.

DISCUSSION: The curricular approach supports exposing students to interprofessional education at an early stage in their training and then to continue with regular reinforcement. Another guiding principle is that interprofessional education is integrative rather than supplementary to the existing core curriculum. Early evaluation results suggest favourable satisfaction amongst students and faculty as well as significant effect on attitudes toward interprofessional teamwork and education. An ongoing evaluation is continuing based upon the various levels of Freeth et al.'s (2002) interprofessional education evaluation framework.}, } @article {pmid18076502, year = {2007}, author = {Willis, HH and Dekay, ML}, title = {The roles of group membership, beliefs, and norms in ecological risk perception.}, journal = {Risk analysis : an official publication of the Society for Risk Analysis}, volume = {27}, number = {5}, pages = {1365-1380}, doi = {10.1111/j.1539-6924.2007.00958.x}, pmid = {18076502}, issn = {0272-4332}, mesh = {Adult ; Aged ; Data Collection ; Ecology ; *Ecosystem ; Environment ; Female ; Group Structure ; Humans ; Male ; Middle Aged ; Perception ; Proportional Hazards Models ; Psychometrics ; Public Policy ; *Risk Assessment ; }, abstract = {Variability in ecological risk perceptions was investigated by surveying members of four stakeholder groups commonly involved in environmental policy debates. Fifty-six individuals from government, industry, environmental, and general-public groups completed a risk-perception survey in which they evaluated 34 environmental hazards on 17 attributes and also evaluated the riskiness and acceptability of each hazard. In addition, participants reported their environmental beliefs and norms using Dunlap et al.'s revised New Ecological Paradigm Scale and modified versions of Schwartz's Awareness of Consequences and Personal Norms Scales. Group membership was predictive of participants' scores on the belief and norm scales. Factor analysis of attribute ratings (averaged across participants) revealed the anticipated three oblique factors: ecological impacts, scientific understanding, and aesthetic impacts. Factor patterns were very similar for the four stakeholder groups. Factors from the aggregate analysis were predictive of individuals' riskiness judgments, but these relationships were moderated by participants' group membership, beliefs, and norms. Compared to members of other groups, members of the general public placed less emphasis on ecological impacts and more emphasis on the other two factors when judging the ecological riskiness of hazards. To our knowledge, these results represent the first formal tests of interactions between hazard characteristics and participant characteristics in determining riskiness judgments, and illustrate how traditional psychometric analyses can be successfully coupled with individual-difference measures to improve the understanding of risk perception.}, } @article {pmid18076480, year = {2007}, author = {Cox, LA}, title = {Regulatory false positives: true, false, or uncertain?.}, journal = {Risk analysis : an official publication of the Society for Risk Analysis}, volume = {27}, number = {5}, pages = {1083-6; author reply 1087-9}, doi = {10.1111/j.1539-6924.2007.00975.x}, pmid = {18076480}, issn = {0272-4332}, mesh = {Environmental Exposure/legislation & jurisprudence/statistics & numerical data ; *Environmental Health/legislation & jurisprudence/statistics & numerical data ; False Positive Reactions ; Humans ; Models, Statistical ; *Risk Assessment/legislation & jurisprudence/statistics & numerical data ; Uncertainty ; }, abstract = {Hansen et al. (2007) recently assessed the historical performance of the precautionary principle in 88 specific cases, concluding that "applying our definition of a regulatory false positive, we were able to identify only four cases that fit the definition of a false positive." Empirically evaluating how prone the precautionary principle is to classify nonproblems as problems ("false positives") is an excellent idea. Yet, Hansen et al.'s implementation of this idea applies a diverse set of questionable criteria to label many highly uncertain risks as "real" even when no real or potential harm has actually been demonstrated. Examples include treating each of the following as reasons to categorize risks as "real": considering that a company's actions contaminated its own product; lack of a known exposure threshold for health effects; occurrence of a threat; treating deliberately conservative (upper-bound) regulatory assumptions as if they were true values; treating assumed exposures of children to contaminated soils (by ingestion) as evidence that feared dioxin risks are real; and treating claimed (sometimes ambiguous) epidemiological associations as if they were known to be true causal relations. Such criteria can classify even nonexistent and unknown risks as "real," providing an alternative possible explanation for why the authors failed to find more false positives, even if they exist.}, } @article {pmid18066922, year = {2008}, author = {Hutton, JM and Perkins, SJ}, title = {A qualitative study of men's experience of myocardial infarction.}, journal = {Psychology, health & medicine}, volume = {13}, number = {1}, pages = {87-97}, doi = {10.1080/13548500701294549}, pmid = {18066922}, issn = {1354-8506}, mesh = {*Adaptation, Psychological ; Adult ; Aged ; Gastroenterology ; Humans ; Interviews as Topic ; Male ; Middle Aged ; Myocardial Infarction/*psychology/rehabilitation ; United Kingdom ; }, abstract = {The majority of people experiencing myocardial infarction and attending cardiac rehabilitation are male and the outcome of rehabilitation is better for men. However, there is a lack of qualitative exploration of how men experience myocardial infarction and cardiac rehabilitation, which this study aims to address. Ten men who had recently had a myocardial infarction were interviewed using a semi-structured format, which covered events around the infarction, its impact on various aspects of life, ways of dealing with these experiences and experience of cardiac rehabilitation and other medical services. In this paper, the themes which emerged from Interpretive Phenomenological Analysis of the interview transcripts will be described and discussed in relation to the existing literature, and particularly to White et al.'s (in press) study of women who had had a myocardial infarction. These themes relate to views of the self, the illness and the future, ways of coping and experiences of rehabilitation. Implications for services and future research will be discussed.}, } @article {pmid18065154, year = {2008}, author = {Nicoletti, JN and Shah, SK and McCloskey, DP and Goodman, JH and Elkady, A and Atassi, H and Hylton, D and Rudge, JS and Scharfman, HE and Croll, SD}, title = {Vascular endothelial growth factor is up-regulated after status epilepticus and protects against seizure-induced neuronal loss in hippocampus.}, journal = {Neuroscience}, volume = {151}, number = {1}, pages = {232-241}, pmid = {18065154}, issn = {0306-4522}, support = {R01 NS037562/NS/NINDS NIH HHS/United States ; R56 NS037562/NS/NINDS NIH HHS/United States ; NS37562/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Blood Vessels/drug effects/ultrastructure ; Cell Death/physiology ; Convulsants ; Enzyme-Linked Immunosorbent Assay ; Hippocampus/cytology/*metabolism/*pathology ; Immunohistochemistry ; In Vitro Techniques ; Infusion Pumps, Implantable ; Male ; Neurons/*metabolism/*pathology ; Neuroprotective Agents ; Pilocarpine ; RNA, Messenger/biosynthesis/genetics ; Rats ; Rats, Sprague-Dawley ; Seizures/chemically induced/*metabolism/*pathology ; Status Epilepticus/chemically induced/*metabolism/*pathology ; Up-Regulation/drug effects ; Vascular Endothelial Growth Factor A/*biosynthesis/pharmacology/*physiology ; }, abstract = {Vascular endothelial growth factor (VEGF) is a protein factor which has been found to play a significant role in both normal and pathological states. Its role as an angiogenic factor is well-established. More recently, VEGF has been shown to protect neurons from cell death both in vivo and in vitro. While VEGF's potential as a protective factor has been demonstrated in hypoxia-ischemia, in vitro excitotoxicity, and motor neuron degeneration, its role in seizure-induced cell loss has received little attention. A potential role in seizures is suggested by Newton et al.'s [Newton SS, Collier EF, Hunsberger J, Adams D, Terwilliger R, Selvanayagam E, Duman RS (2003) Gene profile of electroconvulsive seizures: Induction of neurotrophic and angiogenic factors. J Neurosci 23:10841-10851] finding that VEGF mRNA increases in areas of the brain that are susceptible to cell loss after electroconvulsive-shock induced seizures. Because a linear relationship does not always exist between expression of mRNA and protein, we investigated whether VEGF protein expression increased after pilocarpine-induced status epilepticus. In addition, we administered exogenous VEGF in one experiment and blocked endogenous VEGF in another to determine whether VEGF exerts a neuroprotective effect against status epilepticus-induced cell loss in one vulnerable brain region, the rat hippocampus. Our data revealed that VEGF is dramatically up-regulated in neurons and glia in hippocampus, thalamus, amygdala, and neocortex 24 h after status epilepticus. VEGF induced significant preservation of hippocampal neurons, suggesting that VEGF may play a neuroprotective role following status epilepticus.}, } @article {pmid18055223, year = {2008}, author = {Rossion, B and Jacques, C}, title = {Does physical interstimulus variance account for early electrophysiological face sensitive responses in the human brain? Ten lessons on the N170.}, journal = {NeuroImage}, volume = {39}, number = {4}, pages = {1959-1979}, doi = {10.1016/j.neuroimage.2007.10.011}, pmid = {18055223}, issn = {1053-8119}, mesh = {Brain/*physiology ; Electroencephalography ; Electrophysiology ; *Face ; Humans ; Recognition, Psychology/*physiology ; Visual Perception/*physiology ; }, abstract = {A recent event-related potential (ERP) study (Thierry G., Martin, C.D., Downing, P., Pegna, A.J. 2007. Controlling for interstimulus perceptual variance abolishes N170 face selectivity. Nature Neuroscience, 10, 505-11) claimed that the larger occipito-temporal N170 response to pictures of faces than other categories -- the N170 effect -- is due to a methodological artifact in stimulus selection, specifically, a greater interstimulus physical variance between pictures of objects than faces in previous ERP studies which, when controlled, eliminates this N170 effect. This statement casts doubts on the validity of the conclusions reached by a whole tradition of electrophysiological experiments published over the past 15 years and questions the very interest of using the N170 to probe the time course of face processes in the human brain. Here we claim that this physical variance factor is ill-defined by Thierry et al. and cannot account for previous observations of a smaller N170 amplitude to nonface objects than faces without latency increase and component "smearing". Most importantly, this factor was controlled in previous studies that reported robust N170 effects. We demonstrate that the absence of N170 effect in the study of Thierry et al. is due to methodological flaws in the reported experiments, most notably measuring the N170 at the wrong electrode sites. Moreover, the authors attributed a modulation of N170 amplitude in their study to a differential interstimulus physical variance while it probably reflects a biased comparison of different quality sets of individual images. Here, by taking Thierry et al.'s study as an exemplar case of what should not be done in ERP research of visual categorization processes, we provide clarifications on a number of methodological and theoretical issues about the N170 and its largest amplitude to faces. More generally, we discuss the potential role of differential visual homogeneity of object categories as well as low-level visual properties versus high-level visual processes in accounting for early face-preferential responses and the question of the speed at which visual stimuli are categorized as faces. This survey of the literature points to the N170 as a critical event in the time course of face processes in the human brain.}, } @article {pmid18045365, year = {2007}, author = {Ericsson, KA}, title = {An expert-performance perspective of research on medical expertise: the study of clinical performance.}, journal = {Medical education}, volume = {41}, number = {12}, pages = {1124-1130}, doi = {10.1111/j.1365-2923.2007.02946.x}, pmid = {18045365}, issn = {0308-0110}, mesh = {Clinical Competence/*standards ; Clinical Medicine/*standards ; Decision Making ; Humans ; Physicians/*standards ; Research ; }, abstract = {CONTEXT: Three decades ago Elstein et al. published their classic book on medical expertise, in which they described their failure to identify superior performance by peer-nominated diagnosticians using high- and low-fidelity simulations of the everyday practice of doctors.

OBJECTIVE: This paper reviews the results of subsequent research, with a particular emphasis on the progress toward Elstein et al.'s goal of capturing the essence of superior clinical performance in standardised settings in order to improve clinical practice.

RESULTS: Research following publication of Elstein et al.'s book was influenced by laboratory research in cognitive psychology, which resulted in a redirection of its original focus on capturing clinical performance in practice to studies of changes in cognitive processes as functions of extended clinical experience. There is currently renewed interest in linking laboratory research with studies of the acquisition of superior (expert) performance in the clinic.

CONCLUSIONS: Research on medical expertise and simulation training in technical procedures and diagnosis provide exciting opportunities for establishing translational research on the acquisition of superior (expert) performance in the clinic by capturing it with representative tasks in the laboratory, reproducing it for experimental analysis, and developing training activities, such as deliberate practice, that can induce measurable improvements in performance in the clinic.}, } @article {pmid18037311, year = {2008}, author = {Lavie, P}, title = {Who was the first to use the term Pickwickian in connection with sleepy patients? History of sleep apnoea syndrome.}, journal = {Sleep medicine reviews}, volume = {12}, number = {1}, pages = {5-17}, doi = {10.1016/j.smrv.2007.07.008}, pmid = {18037311}, issn = {1087-0792}, mesh = {Europe ; History, 19th Century ; History, 20th Century ; Humans ; Obesity Hypoventilation Syndrome/*history ; Polysomnography/*history ; Sleep Apnea Syndromes/*history ; United States ; }, abstract = {The symptoms and characteristics of sleep apnoea syndrome--excessive daytime sleepiness, loud snoring, restless and non-restorative sleep--are so impressive that it is difficult to understand why its recognition was delayed until the 1970s. The Centennial book of the American Thoracic Society credited Sidney Burwell for the discovery of Obstructive Sleep Apnoea Syndrome. This is only one of the many mistakes and misattributions regarding the history of sleep apnoea syndrome. The earliest descriptions of patients who presumably suffered from sleep apnoea were made in the 19th century. The term "Pickwickian" in connection with sleepy patients was introduced in 1889. The first electrophysiological sleep recordings of Pickwickian patients and the understanding of the syndrome as disordered breathing in sleep, were made during the late 1950s and 1960s. Its recognition as a public health problem was facilitated by Young et al.'s [Young T, Palta M, Dempsey J, et al. The occurrence of sleep-disordered breathing among middle-aged adults. N Engl J Med 1993;328:1230-5] seminal paper documenting the prevalence of the syndrome in the general population, and by the accumulated evidence that the syndrome is a major cardiovascular risk factor. Bibliometric analysis of the literature on sleep apnoea reveals that future research will focus on the long-term outcomes of the syndrome, on the effects of treatment, and on the underlying mechanisms linking it with cardiovascular morbidity.}, } @article {pmid18033618, year = {2007}, author = {Randhawa, HS and Chowdhary, A and Khanna, G}, title = {Comment on Singh et al.'s 'cryptococcosis in a bandicoot rat'.}, journal = {Medical mycology}, volume = {45}, number = {7}, pages = {655-6; author reply 653-4}, doi = {10.1080/13693780701718167}, pmid = {18033618}, issn = {1369-3786}, mesh = {Animals ; Cryptococcosis/diagnosis/microbiology/*veterinary ; Cryptococcus neoformans/isolation & purification/pathogenicity ; Humans ; Murinae/classification ; Rodent Diseases/*diagnosis/microbiology ; Soil Microbiology ; Virulence ; }, } @article {pmid18031747, year = {2008}, author = {van Rossum, JP}, title = {Commentary on Duimel-Peeters et al.'s (2007), "The effectiveness of massage with and without dimethyl sulfoxide in preventing pressure ulcers: a randomized, double blind cross-over trial in patients prone to pressure ulcers".}, journal = {International journal of nursing studies}, volume = {45}, number = {1}, pages = {154-6; discussion 157-8}, doi = {10.1016/j.ijnurstu.2007.06.010}, pmid = {18031747}, issn = {0020-7489}, mesh = {Clinical Nursing Research ; Cross-Over Studies ; *Data Interpretation, Statistical ; Dimethyl Sulfoxide/*therapeutic use ; Double-Blind Method ; Humans ; Massage/*methods ; *Pilot Projects ; Pressure Ulcer/etiology/*prevention & control ; Randomized Controlled Trials as Topic ; Research Design ; Skin Care/methods ; }, } @article {pmid18030035, year = {2007}, author = {Kerr, MS}, title = {Can an expanded and integrated occupational health service help buffer the impact of a global influenza outbreak in healthcare organizations?.}, journal = {HealthcarePapers}, volume = {8}, number = {1}, pages = {34-7; discussion 50-5}, doi = {10.12927/hcpap.2007.19356}, pmid = {18030035}, issn = {1488-917X}, mesh = {Canada/epidemiology ; Disaster Planning/organization & administration ; Disease Outbreaks/prevention & control ; *Health Facility Administration ; Health Personnel/*organization & administration ; Humans ; Influenza, Human/*epidemiology/*prevention & control ; Occupational Health Services/*organization & administration ; }, abstract = {At first glance, the accompanying article by Silas et al. makes for a somewhat-curious read. The picture they paint of the possible risk of a global pandemic posed by the avian influenza virus H5N1 is indeed a chilling one, not only for the possible extent of the epidemic itself but also because of the likely burden it could place on an already thinly stretched healthcare workforce. It therefore raises a rather alarming contradiction. Given our recent experience of living through the consequences of the outbreak of severe acute respiratory syndrome in Ontario and BC, one would think that we would be more than willing this time around to err on the side of caution and be as prepared as possible to deal with the next emerging infectious agent that comes our way. But, surprisingly, as is carefully outlined in Silas et al.'s paper, this does not seem to be the case. In a healthcare environment that is increasingly focused on the need for evidence upon which to base change in practice, are we possibly dragging our heels in raising our preparedness for a future pandemic? It is an interesting debate, and one that certainly merits further examination.}, } @article {pmid18022042, year = {2007}, author = {Brown, C and Battista, DR and Sereika, SM and Bruehlman, RD and Dunbar-Jacob, J and Thase, ME}, title = {Primary care patients' personal illness models for depression: relationship to coping behavior and functional disability.}, journal = {General hospital psychiatry}, volume = {29}, number = {6}, pages = {492-500}, pmid = {18022042}, issn = {0163-8343}, support = {R01 MH060763/MH/NIMH NIH HHS/United States ; R01 MH 60763/MH/NIMH NIH HHS/United States ; }, mesh = {*Adaptation, Psychological ; Adolescent ; Demography ; Depression/*psychology ; *Disability Evaluation ; Female ; Humans ; Male ; Middle Aged ; *Primary Health Care ; Severity of Illness Index ; *Sick Role ; Surveys and Questionnaires ; }, abstract = {OBJECTIVE: The applicability and clinical utility of Leventhal et al.'s model of illness cognition were evaluated in depressed primary care patients. The intercorrelations of illness beliefs and the mediational effects of coping behavior on these beliefs were also evaluated. Moderating effects of coping behaviors were explored.

METHODS: Baseline evaluations of demographic information, depression diagnoses, depressive symptom severity, self-reported psychosocial and physical functioning, medical comorbidity, illness beliefs and depression coping strategies were obtained from 191 primary care patients receiving antidepressant medication for the treatment of depression.

RESULTS: Patients' beliefs about depressive symptoms, causes, duration as well as controllability and the consequences of these symptoms are described. Leventhal et al.'s mediational model was partially supported for the outcome of psychosocial functioning. Coping behavior did not mediate the relationship between illness beliefs and physical functioning. The relationships between participants' beliefs about the cause, controllability and duration of depressive symptoms were mediated by the use of behavioral disengagement, venting or self-blame as a strategy to cope with depression. In addition, use of acceptance, religious coping or behavioral disengagement moderated the relationship between beliefs about the cause of depression (i.e., environment or chance or medical illness) and psychosocial functioning.

CONCLUSIONS: Illness models for depression are important determinants of functioning in depressed primary care patients. These beliefs and coping behaviors are potentially modifiable and could be the target of interventions to decrease functional impairment in depressed patients.}, } @article {pmid18020785, year = {2007}, author = {Leong, FT}, title = {Cultural accommodation as method and metaphor.}, journal = {The American psychologist}, volume = {62}, number = {8}, pages = {913-927}, doi = {10.1037/0003-066X.62.8.916}, pmid = {18020785}, issn = {0003-066X}, mesh = {Asia ; Asian ; *Awards and Prizes ; Cultural Diversity ; *Culture ; History, 20th Century ; History, 21st Century ; Humans ; International Cooperation ; Male ; *Metaphor ; Minority Health/*history ; Psychology/history ; Psychotherapy/*history/*methods ; United States ; }, abstract = {The author summarizes the cultural accommodation model (CAM) of cross-cultural psychotherapy (F. T. L. Leong & S. H. Lee, 2006). This summary is divided into 2 parts, with the 1st part describing the theoretical development of the CAM as a method of psychotherapy and the research approach underlying it. This section includes a description of the author's program of research in which the development of the CAM, as well as its precursors, is embedded. L. H. Rogler, R. G. Malgady, and O. Rodriguez's (1989) framework has served as the foundation of the author's program of research on Asian American mental health. In focusing on the 4th stage of L. H. Rogler et al.'s model, F. T. L. Leong (1996) developed an integrative and multidimensional model of cross-cultural psychotherapy based on C. Kluckhohn and H. A. Murray's (1950) tripartite model. The CAM is an extension of F. T. L. Leong's (1996) integrative multidimensional model. The 2nd part of this article provides some speculation about the development of the CAM as a metaphor for the author's development as a psychotherapist and a psychological scientist.}, } @article {pmid18020664, year = {2007}, author = {Mongan, J and Svrcek-Seiler, WA and Onufriev, A}, title = {Analysis of integral expressions for effective Born radii.}, journal = {The Journal of chemical physics}, volume = {127}, number = {18}, pages = {185101}, doi = {10.1063/1.2783847}, pmid = {18020664}, issn = {0021-9606}, support = {C06 RR-017588-01/RR/NCRR NIH HHS/United States ; }, mesh = {*Models, Molecular ; Muramidase/chemistry ; Proteins/*chemistry ; Solvents/chemistry ; *Thermodynamics ; Thioredoxins/chemistry ; }, abstract = {Generalized Born (GB) models provide a computationally efficient means of representing the electrostatic effects of solvent and are widely used, especially in molecular dynamics (MD). Accurate and facile computation of the effective Born radii is a key for the performance of GB models. Here, we examine a simple integral prescription, R6, based on the exact solution of the Poisson-Boltzmann (PB) equation for a perfect sphere. Numerical tests on 22 molecules representing a variety of structural classes show that R6 may be more accurate than the more complex integral-based approaches such as GBMV2. At the same time, R6 is computationally less demanding. Fundamental limitations of current integration-based methods for calculating effective radii, including R6, are explored and the deviations from the numerical PB results are correlated with specific topological and geometrical features of the molecular surface. A small systematic bias observed in the R6-based radii can be removed with a single, transferable constant offset; when the resulting effective radii are used in the "classical" (Still et al.'s) GB formula to compute the electrostatic solvation free energy, the average deviation from the PB reference is no greater than when the "perfect" (PB-based) effective radii are used. This deviation is also appreciably smaller than the uncertainty of the PB reference itself, as estimated by comparison to explicit solvent.}, } @article {pmid18018978, year = {2007}, author = {Kuhn, G and Benson, V}, title = {The influence of eye-gaze and arrow pointing distractor cues on voluntary eye movements.}, journal = {Perception & psychophysics}, volume = {69}, number = {6}, pages = {966-971}, doi = {10.3758/bf03193934}, pmid = {18018978}, issn = {0031-5117}, mesh = {Adult ; *Attention ; *Cues ; *Eye Movements ; Female ; *Fixation, Ocular ; Humans ; Male ; *Visual Perception ; }, abstract = {We investigated Ricciardelli et al.'s (2002) claim, that the tendency for gaze direction to elicit automatic attentional following is unique to biologically significant information. Participants made voluntary saccades to targets on the left or the right of a display, which were either congruent or incongruent with a centrally presented distractor (eye-gaze or arrow). Contrary to Ricciardelli et al., for both distractor types, saccade latencies were slower, and participants made more directional errors, on incongruent than on congruent trials. Moreover, a cost-benefit analysis showed no difference between the two distractor types. However, latencies for erroneous saccades were faster than correctly directed saccades for the eye-gaze distractors, but not for the arrow distractors.}, } @article {pmid17908587, year = {2007}, author = {Cong, X and Cox, DD and Cantor, SB}, title = {Bayesian meta-analysis of Papanicolaou smear accuracy.}, journal = {Gynecologic oncology}, volume = {107}, number = {1 Suppl 1}, pages = {S133-7}, pmid = {17908587}, issn = {0090-8258}, support = {P01 CA082710/CA/NCI NIH HHS/United States ; CA82710/CA/NCI NIH HHS/United States ; }, mesh = {Bayes Theorem ; Female ; Humans ; *Papanicolaou Test ; Sensitivity and Specificity ; Uterine Cervical Neoplasms/diagnosis/*pathology ; Vaginal Smears/*standards ; }, abstract = {OBJECTIVE: To perform a Bayesian analysis of data from a previous meta-analysis of Papanicolaou (Pap) smear accuracy (Fahey et al. Am J Epidemiol 1995; 141:680-689) and compare the results.

METHODS: We considered two Bayesian models for the same data set used in the Fahey et al. study. Model I was a beta-binomial model which considered the number of true positives and false negatives as independent binomial random variables with probability parameters beta (sensitivity) and alpha (one minus specificity), respectively. We assumed that beta and alpha are independent, each following a beta distribution with exponential priors. Model II considered sensitivity and specificity jointly through a bivariate normal distribution on the logits of the sensitivity and specificity. We performed sensitivity analysis to examine the effect of prior selection on the parameter estimates.

RESULTS: We compared the estimates of average sensitivity and specificity from the Bayesian models with those from Fahey et al.'s summary receiver operating characteristics (SROC) approach. Model I produced results similar to those of the SROC approach. Model II produced point estimates higher than those of the SROC approach, although the credible intervals overlapped and were wider. Sensitivity analysis showed that the Bayesian models are somewhat sensitive to the variance of the prior distribution, but their point estimates are more robust than those of the SROC approach.

CONCLUSIONS: The Bayesian approach has advantages over the SROC approach in that it accounts for between-study variation and allows for estimating the sensitivity and specificity for a particular trial, taking into consideration the results of other trials, i.e., "borrowing strength" from other trials.}, } @article {pmid18001226, year = {2007}, author = {Bagby, RM and Taylor, GJ and Quilty, LC and Parker, JD}, title = {Reexamining the factor structure of the 20-item Toronto alexithymia scale: commentary on Gignac, Palmer, and Stough.}, journal = {Journal of personality assessment}, volume = {89}, number = {3}, pages = {258-264}, doi = {10.1080/00223890701629771}, pmid = {18001226}, issn = {0022-3891}, mesh = {Affective Symptoms/*classification/*diagnosis/psychology ; Diagnosis, Differential ; Empirical Research ; Factor Analysis, Statistical ; Female ; Humans ; Male ; Personality Assessment/*statistics & numerical data ; Psychometrics/instrumentation ; Reference Values ; Reproducibility of Results ; }, abstract = {Gignac, Palmer, and Stough (2007/this issue) test a number of different latent factor models for the TAS-20 using a community sample of 355 participants and conclude that this scale is best represented by a "nested factors model," with five substantive factors and a method factor. Gignac et al. also report that the correlated three-factor model and a comparable higher order model supported by most studies produced poor levels of incremental close fit. In this article, we challenge Gignac et al.'s unheralded and largely unsupported use of nested model fitting and the uncritical acceptance of exceptionally high cutoff levels to assess goodness of fit (GOF). Using more traditional and empirically supported model testing procedures and a more flexible approach to the interpretation of multiple tests of GOF, we interpret Gignac et al.'s results as actually supportive of the traditional three-factor model and one that has been recovered in 17 of the 24 factor analytic studies of the TAS-20.}, } @article {pmid17999485, year = {2007}, author = {Balasubramanian, K and Cao, Z}, title = {Theoretical studies on structures of neptunyl carbonates: NpO2(CO3)m(H2O)n(q-) (m = 1-3, n = 0-3) in aqueous solution.}, journal = {Inorganic chemistry}, volume = {46}, number = {25}, pages = {10510-10519}, doi = {10.1021/ic700486u}, pmid = {17999485}, issn = {0020-1669}, mesh = {Carbonates/*chemistry ; Models, Molecular ; Molecular Conformation ; Neptunium/*chemistry ; Oxygen/*chemistry ; Solutions ; Spectrophotometry, Infrared ; Water/*chemistry ; }, abstract = {Extensive ab inito computations have been carried out to study the equilibrium structure, infrared spectra, and bonding characteristics of a variety of hydrated NpO2(CO3)m(q-) complexes by considering the solvent as a polarizable dielectric continuum as well as the corresponding anhydrate complexes in the gas phase. The computed structural parameters and vibrational results at the MP2 level in aqueous solution are in good agreement with Clark et al.'s experiments and provide realistic pictures of the neptunyl complexes in an aqueous environment. Our computed hydration energies reveal that the complex with water molecules directly bound to it yields the best results. Our analysis of the nature of the bonding of neptunyl complexes provides insight into the nature of 6d and 5f bonding in actinide complexes.}, } @article {pmid17999225, year = {2007}, author = {Richards, MM and Steele, RG}, title = {Children's self-reported coping strategies: the role of defensiveness and repressive adaptation.}, journal = {Anxiety, stress, and coping}, volume = {20}, number = {2}, pages = {209-222}, doi = {10.1080/10615800701303298}, pmid = {17999225}, issn = {1477-2205}, mesh = {*Adaptation, Psychological ; Adolescent ; Anxiety/psychology ; Child ; *Defense Mechanisms ; Female ; Humans ; Male ; Multivariate Analysis ; *Psychology, Adolescent ; *Psychology, Child ; *Repression, Psychology ; Social Desirability ; Stress, Psychological/psychology ; United States ; }, abstract = {This study examined differences in self-reported coping strategies across children classified according to Weinberger et al.'s (1979) adaptive style paradigm. Consistent with the larger literature, it was hypothesized that repressors (i.e. characterized by high self-reported defensiveness and low self-reported distress) would endorse fewer behaviorally and cognitively avoidant coping strategies than other adaptive style groups. Participants included 134 children, ranging in age from 10 to 13 (M=11.26, sd=.59), who completed measures of defensiveness, trait anxiety, and coping. Consistent with the hypotheses, results indicated significantly lower endorsement of avoidant coping strategies, and significantly higher endorsement of approach-oriented strategies among repressors, but no significant differences across adaptive style groups for other forms of coping. Results indicate that, consistent with other indicators of psychological functioning, the measurement of coping strategies is subject to the effects of socially desirable responding. Further, results provide evidence that measures of coping may be contaminated by items reflecting adjustment problems.}, } @article {pmid17999167, year = {2008}, author = {Tien, JH and Guckenheimer, J}, title = {Parameter estimation for bursting neural models.}, journal = {Journal of computational neuroscience}, volume = {24}, number = {3}, pages = {358-373}, pmid = {17999167}, issn = {1573-6873}, mesh = {Animals ; Brain/physiology ; Electrophysiology/methods ; Models, Neurological ; Neurons/drug effects/*physiology ; Norepinephrine/pharmacology ; Potassium Channels/physiology ; }, abstract = {This paper presents work on parameter estimation methods for bursting neural models. In our approach we use both geometrical features specific to bursting, as well as general features such as periodic orbits and their bifurcations. We use the geometry underlying bursting to introduce defining equations for burst initiation and termination, and restrict the estimation algorithms to the space of bursting periodic orbits when trying to fit periodic burst data. These geometrical ideas are combined with automatic differentiation to accurately compute parameter sensitivities for the burst timing and period. In addition to being of inherent interest, these sensitivities are used in standard gradient-based optimization algorithms to fit model burst duration and period to data. As an application, we fit Butera et al.'s (Journal of Neurophysiology 81, 382-397, 1999) model of preBötzinger complex neurons to empirical data both in control conditions and when the neuromodulator norepinephrine is added (Viemari and Ramirez, Journal of Neurophysiology 95, 2070-2082, 2006). The results suggest possible modulatory mechanisms in the preBötzinger complex, including modulation of the persistent sodium current.}, } @article {pmid17997637, year = {2007}, author = {May, KA and Hess, RF}, title = {Ladder contours are undetectable in the periphery: a crowding effect?.}, journal = {Journal of vision}, volume = {7}, number = {13}, pages = {9.1-15}, doi = {10.1167/7.13.9}, pmid = {17997637}, issn = {1534-7362}, mesh = {Adult ; Algorithms ; Computer Simulation ; Form Perception/*physiology ; Fovea Centralis/physiology ; Humans ; Male ; Models, Biological ; Orientation ; *Perceptual Masking ; Photic Stimulation/methods ; Psychophysics ; }, abstract = {We studied the perceptual integration of contours consisting of Gabor elements positioned along a smooth path, embedded among distractor elements. Contour elements either formed tangents to the path ("snakes") or were perpendicular to it ("ladders"). Perfectly straight snakes and ladders were easily detected in the fovea but, at an eccentricity of 6 degrees , only the snakes were detectable. The disproportionate impairment of peripheral ladder detection remained when we brought foveal performance away from ceiling by jittering the orientations of the elements. We propose that the failure to detect peripheral ladders is a form of crowding, the phenomenon observed when identification of peripherally located letters is disrupted by flanking letters. D. G. Pelli, M. Palomares, and N. J. Majaj (2004) outlined a model in which simple feature detectors are followed by integration fields, which are involved in tasks, such as letter identification, that require the outputs of several detectors. They proposed that crowding occurs because small integration fields are absent from the periphery, leading to inappropriate feature integration by large peripheral integration fields. We argue that the "association field," which has been proposed to mediate contour integration (D. J. Field, A. Hayes, & R. F. Hess, 1993), is a type of integration field. Our data are explained by an elaboration of Pelli et al.'s model, in which weak ladder integration competes with strong snake integration. In the fovea, the association fields were small, and the model integrated snakes and ladders with little interference. In the periphery, the association fields were large, and integration of ladders was severely disrupted by interference from spurious snake contours. In contrast, the model easily detected snake contours in the periphery. In a further demonstration of the possible link between contour integration and crowding, we ran our contour integration model on groups of three-letter stimuli made from short line segments. Our model showed several key properties of crowding: The critical spacing for crowding to occur was independent of the size of the target letter, scaled with eccentricity, and was greater on the peripheral side of the target.}, } @article {pmid17990509, year = {2007}, author = {Sontag, D and Singh, R and Berger, B}, title = {Probabilistic modeling of systematic errors in two-hybrid experiments.}, journal = {Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing}, volume = {}, number = {}, pages = {445-457}, pmid = {17990509}, issn = {2335-6928}, mesh = {Algorithms ; Animals ; Computational Biology ; Humans ; Markov Chains ; Models, Statistical ; Monte Carlo Method ; Protein Interaction Mapping/statistics & numerical data ; Two-Hybrid System Techniques/*statistics & numerical data ; }, abstract = {UNLABELLED: We describe a novel probabilistic approach to estimating errors in two-hybrid (2H) experiments. Such experiments are frequently used to elucidate protein-protein interaction networks in a high-throughput fashion; however, a significant challenge with these is their relatively high error rate, specifically, a high false-positive rate. We describe a comprehensive error model for 2H data, accounting for both random and systematic errors. The latter arise from limitations of the 2H experimental protocol: in theory, the reporting mechanism of a 2H experiment should be activated if and only if the two proteins being tested truly interact; in practice, even in the absence of a true interaction, it may be activated by some proteins - either by themselves or through promiscuous interaction with other proteins. We describe a probabilistic relational model that explicitly models the above phenomenon and use Markov Chain Monte Carlo (MCMC) algorithms to compute both the probability of an observed 2H interaction being true as well as the probability of individual proteins being self-activating/promiscuous. This is the first approach that explicitly models systematic errors in protein-protein interaction data; in contrast, previous work on this topic has modeled errors as being independent and random. By explicitly modeling the sources of noise in 2H systems, we find that we are better able to make use of the available experimental data. In comparison with Bader et al.'s method for estimating confidence in 2H predicted interactions, the proposed method performed 5-10% better overall, and in particular regimes improved prediction accuracy by as much as 76%.

SUPPLEMENTARY INFORMATION: http://theory.csail.mit.edu/probmod2H}, } @article {pmid17990301, year = {2009}, author = {Burge, J and Lane, T and Link, H and Qiu, S and Clark, VP}, title = {Discrete dynamic Bayesian network analysis of fMRI data.}, journal = {Human brain mapping}, volume = {30}, number = {1}, pages = {122-137}, pmid = {17990301}, issn = {1097-0193}, support = {R01 DA012852/DA/NIDA NIH HHS/United States ; R01 MH076282/MH/NIMH NIH HHS/United States ; 1R01MH076282/MH/NIMH NIH HHS/United States ; 1R01DA12852/DA/NIDA NIH HHS/United States ; }, mesh = {Aged ; Algorithms ; Alzheimer Disease/pathology/physiopathology ; Bayes Theorem ; Brain/anatomy & histology/physiology ; Brain Mapping/methods ; Cerebrovascular Circulation/physiology ; Data Interpretation, Statistical ; Fourier Analysis ; Humans ; Image Processing, Computer-Assisted/*methods ; Magnetic Resonance Imaging/*methods ; Nerve Net/anatomy & histology/physiology ; *Neural Networks, Computer ; Normal Distribution ; *Signal Processing, Computer-Assisted ; }, abstract = {We examine the efficacy of using discrete Dynamic Bayesian Networks (dDBNs), a data-driven modeling technique employed in machine learning, to identify functional correlations among neuroanatomical regions of interest. Unlike many neuroimaging analysis techniques, this method is not limited by linear and/or Gaussian noise assumptions. It achieves this by modeling the time series of neuroanatomical regions as discrete, as opposed to continuous, random variables with multinomial distributions. We demonstrated this method using an fMRI dataset collected from healthy and demented elderly subjects (Buckner, et al., 2000: J Cogn Neurosci 12:24-34) and identify correlates based on a diagnosis of dementia. The results are validated in three ways. First, the elicited correlates are shown to be robust over leave-one-out cross-validation and, via a Fourier bootstrapping method, that they were not likely due to random chance. Second, the dDBNs identified correlates that would be expected given the experimental paradigm. Third, the dDBN's ability to predict dementia is competitive with two commonly employed machine-learning classifiers: the support vector machine and the Gaussian naive Bayesian network. We also verify that the dDBN selects correlates based on non-linear criteria. Finally, we provide a brief analysis of the correlates elicited from Buckner et al.'s data that suggests that demented elderly subjects have reduced involvement of entorhinal and occipital cortex and greater involvement of the parietal lobe and amygdala in brain activity compared with healthy elderly (as measured via functional correlations among BOLD measurements). Limitations and extensions to the dDBN method are discussed.}, } @article {pmid17985878, year = {2007}, author = {Gómora-Figueroa, AP and Jancik, V and Cea-Olivares, R and Toscano, RA}, title = {An unknown coordination mode of the phosphite unit and a carbon-free heterocycle in two different heterobimetallic alumophosphites.}, journal = {Inorganic chemistry}, volume = {46}, number = {25}, pages = {10749-10753}, doi = {10.1021/ic701614c}, pmid = {17985878}, issn = {0020-1669}, abstract = {The unique alumophosphite reagent LAl(SH)(mu-O)P(OEt)2 was prepared and used for the synthesis of the heterobimetallic alumophosphites [{kappa2-S,P-LAl(S)(mu-O)P(OEt)2} 2Zn] and [{kappa4-S,O,O-LAl(SLi)(mu-O)P(OEt)2} 2]. The first contains a rare example of two carbon-free five-membered heterocycles (Al-S-Zn-P-O) connected in a spiro fashion through the zinc atom, whereas the second possesses an unknown example of a coordination environment of a phosphite unit M-O-P(mu-OEt)2M with an uncoordinated lone electron pair on the phosphorus center.}, } @article {pmid17983768, year = {2008}, author = {Danquah, AN and Farrell, MJ and O'Boyle, DJ}, title = {Biases in the subjective timing of perceptual events: Libet et al. (1983) revisited.}, journal = {Consciousness and cognition}, volume = {17}, number = {3}, pages = {616-627}, doi = {10.1016/j.concog.2007.09.005}, pmid = {17983768}, issn = {1090-2376}, mesh = {Adult ; Brain/*physiology ; *Consciousness ; Electroencephalography ; Female ; Humans ; *Intention ; Male ; Movement ; Reaction Time ; *Time Perception ; Unconscious, Psychology ; }, abstract = {We report two experiments in which participants had to judge the time of occurrence of a stimulus relative to a clock. The experiments were based on the control condition used by Libet, Gleason, Wright, and Pearl [Libet, B., Gleason, C. A., Wright, E. W., & Pearl, D. K. (1983). Time of conscious intention to act in relation to onset of cerebral activities (readiness-potential): The unconscious initiation of a freely voluntary act. Brain 106, 623-642] to correct for any bias in the estimation of the time at which an endogenous event, the conscious intention to perform a movement, occurred. Participants' responses were affected systematically by the sensory modality of the stimulus and by the speed of the clock. Such findings demonstrate the variability in judging the time at which an exogenous event occurs and, by extension, suggest that such variability may also apply to the judging the time of occurrence of endogenous events. The reliability of participants' estimations of when they formed the conscious intention to perform a movement in Libet et al.'s (1983) study is therefore questionable.}, } @article {pmid17980551, year = {2008}, author = {Lowe, SS and Nekolaichuk, CL and Fainsinger, RL and Lawlor, PG}, title = {Should the rate of opioid dose escalation be included as a feature in a cancer pain classification system?.}, journal = {Journal of pain and symptom management}, volume = {35}, number = {1}, pages = {51-57}, doi = {10.1016/j.jpainsymman.2007.02.044}, pmid = {17980551}, issn = {0885-3924}, mesh = {Adult ; Age Factors ; Aged ; Analgesics, Opioid/*administration & dosage/*therapeutic use ; Female ; Humans ; Male ; Middle Aged ; Neoplasms/*classification/complications ; Pain/*classification/*drug therapy/etiology ; Retrospective Studies ; Socioeconomic Factors ; }, abstract = {The purpose of this study was to assess the need for opioid dose escalation as a feature of a pain classification system for advanced cancer patients. Opioid dose escalation was included as a prognostic feature in the original Edmonton Staging System (ESS) for pain classification, but was not included among the five features of the revised ESS (rESS): pain mechanism, incident pain, psychological distress, addictive behavior, and cognitive function. Mercadante et al.'s definition of opioid escalation index percentage (OEI%) has been used as a surrogate marker for opioid responsiveness. Our hypothesis was that younger age (<60 years), neuropathic pain, incident pain, psychological distress, and addictive behavior would be associated with an OEI% >5%. Using data from a recent multicenter validation study of the rESS, a secondary analysis of a subsample of 532 advanced cancer patients with a pain syndrome was conducted. Approximately 44% (n=232) of the patients had an OEI% >5%. There were no significant associations between OEI% and age, neuropathic pain, incident pain, psychological distress, or addictive behavior. As originally proposed as a clinical marker, the OEI% may oversimplify the complexity of pain management in advanced cancer patients. Future studies are required to better elucidate the need for opioid dose escalation as a feature of a cancer pain classification system.}, } @article {pmid17972748, year = {2007}, author = {Rubin, DC and Berntsen, D}, title = {People believe it is plausible to have forgotten memories of childhood sexual abuse.}, journal = {Psychonomic bulletin & review}, volume = {14}, number = {4}, pages = {776-778}, pmid = {17972748}, issn = {1069-9384}, support = {R01 MH066079/MH/NIMH NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; *Attitude ; *Child Abuse, Sexual/statistics & numerical data ; *Culture ; Female ; Humans ; Male ; *Memory ; Middle Aged ; *Repression, Psychology ; }, abstract = {Pezdek, Blandon-Gitlin, and Gabbay (2006) found that perceptions of the plausibility of events increase the likelihood that imagination may induce false memories of those events. Using a survey conducted by Gallup, we asked a large sample of the general population how plausible it would be for a person with longstanding emotional problems and a need for psychotherapy to be a victim of childhood sexual abuse, even though the person could not remember the abuse. Only 18% indicated that it was implausible or very implausible, whereas 67% indicated that such an occurrence was either plausible or very plausible. Combined with Pezdek et al.s' findings, and counter to their conclusions, our findings imply that there is a substantial danger of inducing false memories of childhood sexual abuse through imagination in psychotherapy.}, } @article {pmid17972293, year = {2007}, author = {Alley, PJ and Allen, RA and Leverett, JP}, title = {Validity of two selected-item short forms of the WAIS-III in an intellectually deficient sample.}, journal = {Journal of clinical psychology}, volume = {63}, number = {12}, pages = {1145-1152}, doi = {10.1002/jclp.20410}, pmid = {17972293}, issn = {0021-9762}, mesh = {Adolescent ; Adult ; Chi-Square Distribution ; Humans ; Intellectual Disability/classification/*diagnosis/psychology ; Middle Aged ; Psychometrics ; Reproducibility of Results ; Wechsler Scales/*statistics & numerical data ; }, abstract = {Various short forms of the Wechsler Adult Intelligence Scale-Third Edition (WAIS-III; D. Wechsler, 1997) have been investigated, but limited information is available regarding the usefulness of any WAIS-III abbreviation with intellectually deficient individuals. Our study compared the validities of two WAIS-III selected-item short forms in a sample of 59 individuals with full scale IQs (FSIQs) of 79 or lower. The performance of both short forms was adequate, but the results gave a consistent edge to an adapted version of the Satz-Mogel (1962) short form in comparison to the abbreviated form by J. H. Wymer, K. Rayls, and M. T. Wagner (2003). The correlation (r = .98) of Satz-Mogel estimates with WAIS-III FSIQ scores was slightly higher than the correlation (r = .97) for estimates from Wymer et al.'s abbreviated form, and Satz-Mogel estimates did not differ significantly from actual FSIQs. In comparison to individual classification (FSIQ > 70 versus FSIQ < or = 70) obtained with the full WAIS-III, the misclassification rate was somewhat lower for the Satz-Mogel short form. Although both short forms performed reasonably well, practitioners should be cautious when utilizing any short form to make decisions about individuals.}, } @article {pmid17952714, year = {2007}, author = {Strom, TQ and Kosciulek, J}, title = {Stress, appraisal and coping following mild traumatic brain injury.}, journal = {Brain injury}, volume = {21}, number = {11}, pages = {1137-1145}, doi = {10.1080/02699050701687334}, pmid = {17952714}, issn = {0269-9052}, mesh = {*Adaptation, Psychological ; Adolescent ; Adult ; Aged ; Brain Injuries/*psychology ; Depression/etiology/psychology ; Female ; Glasgow Coma Scale ; Humans ; Male ; Middle Aged ; *Models, Psychological ; Motivation ; Neuropsychological Tests ; Quality of Life ; Stress, Psychological/*etiology ; }, abstract = {PURPOSE: The present study tested a portion of the stress, appraisal and coping (SAC) model proposed by Godfrey, Knight and Partridge.

METHODS: Using data gathered from 94 individuals who had sustained a traumatic brain injury, path analysis results indicated that a model based on Godfrey et al.'s SAC model did not fit the sample data. Based on relevant statistical output, previous research and theory, a re-specified model was tested.

RESULTS: The final model was shown to meet common statistical measures for establishing model fit. The final model indicated that higher levels of perceived stress were predictive of higher levels of self-reported depression, higher levels of depression were predictive of lower levels of dispositional hope and dispositional hope was predictive of increased life satisfaction and work productivity.

CONCLUSIONS: The present findings hold implications for both research and for clinical practice. The findings do suggest the need for additional research to further clarify factors that contribute to emotional adjustment following traumatic brain injury.}, } @article {pmid17928036, year = {2008}, author = {Ehrman, JM and Bärlocher, F and Wennrich, R and Krauss, GJ and Krauss, G}, title = {Fungi in a heavy metal precipitating stream in the Mansfeld mining district, Germany.}, journal = {The Science of the total environment}, volume = {389}, number = {2-3}, pages = {486-496}, doi = {10.1016/j.scitotenv.2007.09.004}, pmid = {17928036}, issn = {0048-9697}, mesh = {Alnus/chemistry/microbiology/ultrastructure ; Chemical Precipitation ; Environmental Monitoring/*methods ; *Fresh Water/analysis/microbiology ; Fungi/*growth & development ; Germany ; Metals, Heavy/*analysis ; Microscopy, Electron, Scanning ; Mining ; Plant Leaves/chemistry/microbiology/ultrastructure ; *Water Microbiology ; Water Pollutants, Chemical/*analysis ; }, abstract = {Fungal growth on alder leaves was studied in two heavy metal polluted streams in central Germany. The aim of the study was to examine previously observed differences in leaf decomposition rates, heavy metal precipitation and fungal involvement in these processes at the microscopic level. Ergosterol analyses indicated that neither habitat was optimal for fungi, but leaves exposed at the less polluted site (H8) decomposed rapidly and were colonized externally and internally by fungi and other microorganisms. Leaves exposed at the more polluted site (H4) decomposed very slowly and fungal colonization was restricted to external surfaces. An amorphous organic layer, deposited within 24 h of exposure, quickly became covered with a pale blue-green crystalline deposit (zincowoodwardite) with significant amounts of Al, S, Cu and Zn, determined by energy dispersive X-ray spectroscopy (EDS). Scanning electron microscopy (SEM) analysis of the precipitate revealed a branching arrangement of the precipitated particles caused by the presence of fungal hyphae growing on the surface. Hyphae that were not disturbed by handling were usually completely encased in the precipitate, but hyphae did not contain EDS-detectable amounts of precipitate metals. Elemental analysis using inductively coupled plasma (ICP) atomic emission spectrometry and ICP mass spectrometry revealed continuing accumulation of Zn, Cu and several other metals/metalloids on and in leaves. The formation of metal precipitates on various artificial substrates at site H4 was much reduced compared to leaves, which we attribute to the absence of fungal colonization on the artificial substrates. We could not determine whether fungi accelerate the precipitation of heavy metals at site H4, but mycelial growth on leaves continues to create new surfaces and therefore thicker layers of precipitate on leaves compared to artificial substrates.}, } @article {pmid17910174, year = {2007}, author = {Maddox, WT and Lauritzen, JS and Ing, AD}, title = {Cognitive complexity effects in perceptual classification are dissociable.}, journal = {Memory & cognition}, volume = {35}, number = {5}, pages = {885-894}, pmid = {17910174}, issn = {0090-502X}, support = {AFOSR FA9550-06-1-0204//PHS HHS/United States ; R01 MH59196/MH/NIMH NIH HHS/United States ; }, mesh = {Classification ; *Cognition ; Humans ; *Perception ; }, abstract = {It has been proposed that a procedural-based classification system mediates the learning of information-integration categories, whereas a hypothesis-testing system mediates the learning of rule-based categories. Ashby, Ell and Waldron (2003) provided support for this claim by showing that a button switch introduced during classification transfer adversely affected information-integration but not rule-based performance. Nosofsky, Stanton and Zaki (2005) showed that increasing "cognitive complexity" can lead to button switch costs on rule-based performance. They argue that "cognitive complexity," and not the existence of separable classification systems, accounts for Ashby et al.'s empirical dissociation. The present study shows that experimental manipulations that increase "cognitive complexity" often have dissociable effects on information-integration and rule-based classification that are predicted a priori from the processing characteristics associated with the procedural-based and hypothesis-testing systems. These results suggest that manipulations of "cognitive complexity" can be dissociated, suggesting that "cognitive complexity" in not a unitary construct that affects a single psychological process.}, } @article {pmid17907873, year = {2007}, author = {Blais, C and Robidoux, S and Risko, EF and Besner, D}, title = {Item-specific adaptation and the conflict-monitoring hypothesis: a computational model.}, journal = {Psychological review}, volume = {114}, number = {4}, pages = {1076-1086}, doi = {10.1037/0033-295X.114.4.1076}, pmid = {17907873}, issn = {0033-295X}, mesh = {Cognition/*physiology ; *Conflict, Psychological ; Frontal Lobe/*physiology ; Humans ; }, abstract = {M. M. Botvinick, T. S. Braver, D. M. Barch, C. S. Carter, and J. D. Cohen (2001) implemented their conflict-monitoring hypothesis of cognitive control in a series of computational models. The authors of the current article first demonstrate that M. M. Botvinick et al.'s (2001) conflict-monitoring Stroop model fails to simulate L. L. Jacoby, D. S. Lindsay, and S. Hessels's (2003) report of an item-specific proportion-congruent (ISPC) effect in the Stroop task. The authors then implement a variant of M. M. Botvinick et al.'s model based on the assumption that control must be able to operate at the item level. This model successfully simulates the ISPC effect. In addition, the model provides an alternative to M. M. Botvinick et al.'s explanation of the list-level proportion-congruent effect in terms of an ISPC effect. Implications of the present modeling effort are discussed.}, } @article {pmid17905902, year = {2007}, author = {Auer, ET and Bernstein, LE}, title = {Enhanced visual speech perception in individuals with early-onset hearing impairment.}, journal = {Journal of speech, language, and hearing research : JSLHR}, volume = {50}, number = {5}, pages = {1157-1165}, doi = {10.1044/1092-4388(2007/080)}, pmid = {17905902}, issn = {1092-4388}, support = {DC03633/DC/NIDCD NIH HHS/United States ; R01 DC004856/DC/NIDCD NIH HHS/United States ; DC04856/DC/NIDCD NIH HHS/United States ; DC02107/DC/NIDCD NIH HHS/United States ; DC00695/DC/NIDCD NIH HHS/United States ; }, mesh = {Adult ; Female ; Hearing Loss/*physiopathology ; Humans ; Individuality ; *Lipreading ; Male ; Sex Factors ; }, abstract = {PURPOSE: L. E. Bernstein, M. E. Demorest, and P. E. Tucker (2000) demonstrated enhanced speechreading accuracy in participants with early-onset hearing loss compared with hearing participants. Here, the authors test the generalization of Bernstein et al.'s (2000) result by testing 2 new large samples of participants. The authors also investigated correlates of speechreading ability within the early-onset hearing loss group and gender differences in speechreading ability within both participant groups.

METHOD: One hundred twelve individuals with early-onset hearing loss and 220 individuals with normal hearing identified 30 prerecorded sentences presented 1 at a time from visible speech information alone.

RESULTS: The speechreading accuracy of the participants with early-onset hearing loss (M=43.55% words correct; SD=17.48) significantly exceeded that of the participants with normal hearing (M=18.57% words correct; SD=13.18), t(330)=14.576, p<.01. Within the early-onset hearing loss participants, speechreading ability was correlated with several subjective measures of spoken communication. Effects of gender were not reliably observed.

CONCLUSION: The present results are consistent with the results of Bernstein et al. (2000). The need to rely on visual speech throughout life, and particularly for the acquisition of spoken language by individuals with early-onset hearing loss, can lead to enhanced speechreading ability.}, } @article {pmid17904206, year = {2007}, author = {Pretorius, RG and Belinson, JL}, title = {Letter to the editor concerning Petignat et al.'s "Are self-collected samples comparable to physician-collected cervical specimens for human papillomavirus DNA testing? A systematic review and meta-analysis." Gynecol Oncol 2007;105(2): 530-535.}, journal = {Gynecologic oncology}, volume = {107}, number = {3}, pages = {595-6; author reply 596-7}, doi = {10.1016/j.ygyno.2007.08.068}, pmid = {17904206}, issn = {1095-6859}, mesh = {Cervix Uteri/pathology/*virology ; DNA, Viral/*analysis ; Female ; Humans ; Papillomaviridae/genetics/*isolation & purification ; Papillomavirus Infections/pathology/*virology ; *Self-Examination ; Specimen Handling/*methods ; Vaginal Smears/*methods ; }, } @article {pmid17891729, year = {2007}, author = {Knapczyk, FN and Conner, JK}, title = {Estimates of the average strength of natural selection are not inflated by sampling error or publication bias.}, journal = {The American naturalist}, volume = {170}, number = {4}, pages = {501-508}, doi = {10.1086/521239}, pmid = {17891729}, issn = {1537-5323}, mesh = {Animals ; Plants ; *Publication Bias ; Sample Size ; Selection Bias ; *Selection, Genetic ; }, abstract = {Kingsolver et al.'s review of phenotypic selection gradients from natural populations provided a glimpse of the form and strength of selection in nature and how selection on different organisms and traits varies. Because this review's underlying database could be a key tool for answering fundamental questions concerning natural selection, it has spawned discussion of potential biases inherent in the review process. Here, we explicitly test for two commonly discussed sources of bias: sampling error and publication bias. We model the relationship between variance among selection gradients and sample size that sampling error produces by subsampling large empirical data sets containing measurements of traits and fitness. We find that this relationship was not mimicked by the review data set and therefore conclude that sampling error does not bias estimations of the average strength of selection. Using graphical tests, we find evidence for bias against publishing weak estimates of selection only among very small studies (N<38). However, this evidence is counteracted by excess weak estimates in larger studies. Thus, estimates of average strength of selection from the review are less biased than is often assumed. Devising and conducting straightforward tests for different biases allows concern to be focused on the most troublesome factors.}, } @article {pmid17888392, year = {2007}, author = {He, JH and Mo, LF and Xu, L}, title = {On body size of infected mice.}, journal = {Acta tropica}, volume = {104}, number = {2-3}, pages = {140-141}, doi = {10.1016/j.actatropica.2007.07.012}, pmid = {17888392}, issn = {0001-706X}, mesh = {Algorithms ; Animals ; Body Weight/*physiology ; Male ; Mice ; Models, Theoretical ; Schistosoma mansoni/*growth & development ; Schistosomiasis mansoni/parasitology/*physiopathology ; Time Factors ; }, abstract = {Coutinho et al.'s experimental observation reveals that infected mice gain higher body weight. A theoretical analysis is given to explain the phenomenon, the result agrees remarkably well with Coutinho et al.'s experimental data (Acta Tropica 101, 2007, pp. 15-24).}, } @article {pmid17886262, year = {2008}, author = {Blomberg, K and Ternestedt, BM and Törnberg, S and Tishelman, C}, title = {How do women who choose not to participate in population-based cervical cancer screening reason about their decision?.}, journal = {Psycho-oncology}, volume = {17}, number = {6}, pages = {561-569}, doi = {10.1002/pon.1270}, pmid = {17886262}, issn = {1099-1611}, mesh = {Adult ; *Decision Making ; Female ; Health Knowledge, Attitudes, Practice ; Humans ; Interviews as Topic ; Mass Screening/*psychology ; Middle Aged ; Motivation ; Patient Acceptance of Health Care/*psychology ; Personal Autonomy ; Social Responsibility ; Sweden ; Uterine Cervical Neoplasms/diagnosis/*prevention & control/psychology ; Vaginal Smears/*psychology ; }, abstract = {In Stockholm, Sweden, women are invited to a cost-free population-based cervical cancer screening programme (PCCSP) at regular intervals. Despite this, many women choose not to attend screening at all or to take opportunistic tests instead. This study explores how women who actively declined participation in the PCCSP reasoned about their choice. Qualitative telephone interviews and fax messages from women who actively declined participation in the PCCSP were analysed inductively. The manner in which women defined and conceptualized distinctions between, and the roles and responsibilities of, both private and public spheres were found to be central in explanations of decision making. Factors related to women's decisions not to participate in screening at all include a lack of confidence in the benefits of screening, previous negative health care and preventive experiences, a belief in one's own ability to discern health changes or a belief that one was not at risk for cervical cancer, as well as a number of unconventional standpoints on social and political issues. Women who chose not to participate in the organized PCCSP, but who did use private opportunistic screening, generally motivated this with direct or indirect criticism of the screening programme itself. Not only was the examination itself sensitive but also all facets of the PCCSP, from invitation letter on, were found to influence women's decisions. Using Jepson et al.'s ethical framework to peruse the evidence-base underlying women's 'informed decision-making' about CCS is suggested to be more constructive than discussing potential participants' knowledge versus lack of knowledge.}, } @article {pmid17874581, year = {2007}, author = {Burnham, BR}, title = {Displaywide visual features associated with a search display's appearance can mediate attentional capture.}, journal = {Psychonomic bulletin & review}, volume = {14}, number = {3}, pages = {392-422}, pmid = {17874581}, issn = {1069-9384}, mesh = {*Attention ; Fixation, Ocular ; Humans ; Models, Psychological ; Orientation ; Psychological Tests ; Space Perception ; *Visual Perception ; }, abstract = {Whether or not the capture of visual attention is driven solely by the salience of an attention-capturing stimulus or mediated by top-down control has been a point of contention since Folk, Remington, and Johnston (1992) introduced their contingent involuntary orienting hypothesis, which states that the capture of attention by a salient stimulus depends on its relevance to a feature distinguishing the target from nontargets. Gibson and Kelsey (1998) extended Folk et al.'s (1992) hypothesis by demonstrating that features associated with the appearance of the target display also mediate capture. Although similar to Folk et al. (1992), Gibson and Kelsey's displaywide contingent orienting hypothesis makes it difficult to demonstrate stimulus-driven capture, because an observer must always use some perceptible feature as a signal of the target display's appearance; hence, such features could always be mediating capture. The present article reviews and applies the logic of Gibson and Kelsey's and Folk et al.'s (1992) hypotheses to experiments from the attentional capture literature, and assesses whether previously reported capture effects were mediated by top-down attentional control. It concludes that these capture effects were not stimulus-driven.}, } @article {pmid17870040, year = {2008}, author = {Hartsuiker, RJ and Pickering, MJ}, title = {Language integration in bilingual sentence production.}, journal = {Acta psychologica}, volume = {128}, number = {3}, pages = {479-489}, doi = {10.1016/j.actpsy.2007.08.005}, pmid = {17870040}, issn = {0001-6918}, mesh = {Humans ; *Language ; *Multilingualism ; *Speech Production Measurement ; *Verbal Behavior ; }, abstract = {To what extent are processes used in sentence production integrated between the different languages of a bilingual and to what extent are they kept separate? We consider three models that differ in their assumptions about the degree of integration: De Bot's [De Bot, K. (1992). A bilingual production model: Levelt's Speaking model adapted. Applied Linguistics, 13, 1-24] bilingual blueprint of the speaker, Ullman's [Ullman, M. T. (2001). The neural basis of lexicon and grammar in first and second language: The declarative/procedural model. Bilingualism: Language and Cognition, 4, 105-122] declarative/procedural model of bilingualism, and Hartsuiker et al.'s [Hartsuiker, R. J., Pickering, M. J., & Veltkamp, E. (2004). Is syntax separate or shared between languages? Cross-linguistic syntactic priming in Spanish/English bilinguals. Psychological Science, 15, 409-414] integrated model. A review of the evidence from bilingual sentence production studies shows that Hartsuiker et al.'s predictions are supported, but argues against the other two models. We discuss some repercussions for bilingual language use.}, } @article {pmid17853847, year = {2007}, author = {Lohfeld, L and Brazil, K and Willison, K}, title = {Continuity of care for advanced cancer patients: comparing the views of spousal caregivers in Ontario, Canada, to Dumont et al.'s theoretical model.}, journal = {Journal of palliative care}, volume = {23}, number = {2}, pages = {117-126}, pmid = {17853847}, issn = {0825-8597}, mesh = {Aged ; Aged, 80 and over ; Attitude to Health ; Caregivers/*psychology ; Communication ; Continuity of Patient Care/*organization & administration ; Cooperative Behavior ; Family/*psychology ; Female ; Humans ; Interprofessional Relations ; Male ; Middle Aged ; Models, Psychological ; *Models, Theoretical ; Neoplasms/*psychology/therapy ; Ontario ; Outcome Assessment, Health Care ; Patient Care Team/organization & administration ; Patient Participation/psychology ; Qualitative Research ; Quality Indicators, Health Care ; Surveys and Questionnaires ; }, } @article {pmid17804832, year = {2007}, author = {Berry, K and Drake, R and Stewart, C and Aitkin, LM and Byrne, J and Barrowclough, C and Purandare, N}, title = {Orofacial dyskinesia, frontal lobe dysfunction, and coping in older people with psychosis.}, journal = {The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry}, volume = {15}, number = {9}, pages = {800-806}, doi = {10.1097/JGP.0b013e31806841ae}, pmid = {17804832}, issn = {1064-7481}, mesh = {Adaptation, Psychological/*physiology ; Aged ; Aged, 80 and over ; Emotions ; Female ; Frontal Lobe/*physiology ; Humans ; Male ; Mental Status Schedule ; Movement Disorders/physiopathology/*psychology ; *Neuropsychological Tests ; Problem Solving/physiology ; Psychiatric Status Rating Scales ; Psychotic Disorders/physiopathology/*psychology ; Statistics as Topic ; }, abstract = {OBJECTIVE: To investigate whether orofacial tardive dyskinesia (OTD) is associated with frontal lobe dysfunction and whether either are related to the coping abilities independent of psychiatric symptoms in older people with psychotic disorders.

METHODS: A total of 52 patients, aged over 65 years or over, who satisfied International Classification of Diseases, Tenth Revision criteria for psychotic disorders (F20-F29) were recruited into the study. OTD was measured using the Abnormal Involuntary Movements Scale and Waddington et al.'s (1993) criteria. Neuropsychological measures were specifically selected to assess different aspects of frontal function and coping was measured using a semistructured interview. Psychiatric symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS).

RESULTS: Patients with OTD showed more severe global cognitive impairment compared to patients without OTD. Group differences on measures of frontal lobe dysfunction were not maintained following adjustment for global cognitive impairment. Patients with OTD did not differ from patients without OTD on coping measures. Scores on the general psychopathology subscale of the PANSS, which includes symptoms associated with depression and anxiety, consistently predicted patients' negative perceptions of stressors and appraisals of coping, but cognitive impairment did not predict coping independent of symptoms.

CONCLUSION: The association between coping and general psychopathology in older patients with psychosis warrants further investigation as both variables may be amenable to psychological interventions.}, } @article {pmid17723041, year = {2007}, author = {Burchinal, MR and Clarke-Stewart, KA}, title = {Maternal employment and child cognitive outcomes: the importance of analytic approach.}, journal = {Developmental psychology}, volume = {43}, number = {5}, pages = {1140-1155}, doi = {10.1037/0012-1649.43.5.1140}, pmid = {17723041}, issn = {0012-1649}, mesh = {Child Care/*psychology ; *Child Development ; Child, Preschool ; *Cognition ; Color Perception ; Data Interpretation, Statistical ; Female ; Humans ; Infant ; Infant, Newborn ; *Language Development ; Longitudinal Studies ; Male ; Mothers/*psychology ; Neuropsychological Tests/statistics & numerical data ; Parenting/*psychology ; Pattern Recognition, Visual ; Problem Solving ; Psychometrics/statistics & numerical data ; Reading ; Reproducibility of Results ; United States ; Verbal Learning ; Women, Working/*psychology ; }, abstract = {J. Brooks-Gunn, W. J. Han, and J. Waldfogel (2002) and the National Institute of Child Health and Human Development Early Child Care Research Network (ECCRN; 2000b) came to different conclusions about the effects of maternal employment--although they were addressing similar questions using the same data set. Brooks-Gunn et al. concluded that maternal employment in infancy has a negative effect on children's cognitive abilities at age 3, whereas the ECCRN found that early nonmaternal care is not related to children's cognitive abilities in their first 3 years. The authors account for this difference by comparing 2 approaches to data analysis: a top-down testing of continuous variables (the approach used by the ECCRN, 2000b) and an a priori comparison approach that involves pairwise testing of specific dichotomous contrasts (the approach used by Brooks-Gunn et al., 2002). This comparison illustrates the critical importance of analytic approach. It also suggests that Brooks-Gunn et al.'s conclusion from this data set is overstated and should not be used on its own as the basis for practical or policy decisions.}, } @article {pmid17721970, year = {2007}, author = {Schlenger, WE and Kulka, RA and Fairbank, JA and Hough, RL and Jordan, BK and Marmar, CR and Weiss, DS}, title = {The psychological risks of Vietnam: the NVVRS perspective.}, journal = {Journal of traumatic stress}, volume = {20}, number = {4}, pages = {467-479}, doi = {10.1002/jts.20264}, pmid = {17721970}, issn = {0894-9867}, mesh = {Adaptation, Psychological ; Bias ; Combat Disorders/diagnosis/*epidemiology/*psychology ; Cross-Sectional Studies ; Health Surveys ; Humans ; Male ; Risk ; United States ; Veterans/*psychology ; *Vietnam Conflict ; }, abstract = {In recent years, controversy concerning the psychological consequences of service in the Vietnam war has rearisen. In this article, the Co-Principal Investigators of the National Vietnam Veterans Readjustment Study (NVVRS) provide a perspective on new findings reported by B. P. Dohrenwend et al. (2006) that addresses criticisms of the NVVRS PTSD (posttraumatic stress disorder) prevalence findings, and on a perspective that was provided by R. J. McNally (2006) in an accompanying commentary. They find that Dohrenwend et al.'s study, which evaluated empirically a variety of the critics' alternative explanations and found little support for any of them, represents a landmark contribution to the trauma field. However, they found that McNally's commentary misrepresented the history and context of the NVVRS, and then misinterpreted Dohrenwend et al.'s findings and their importance.}, } @article {pmid17721958, year = {2007}, author = {McNally, RJ}, title = {Revisiting Dohrenwend et al.'s revisit of the National Vietnam Veterans Readjustment Study.}, journal = {Journal of traumatic stress}, volume = {20}, number = {4}, pages = {481-486}, doi = {10.1002/jts.20257}, pmid = {17721958}, issn = {0894-9867}, mesh = {Adaptation, Psychological ; Bias ; Combat Disorders/diagnosis/*epidemiology/*psychology ; Cross-Sectional Studies ; Diagnosis, Differential ; Health Surveys ; Humans ; Male ; United States ; Veterans/*psychology/statistics & numerical data ; *Vietnam Conflict ; }, abstract = {Critics of the National Vietnam Veterans Readjustment Study (NVVRS) suspect that the NVVRS overestimated the prevalence of posttraumatic stress disorder (PTSD) among Vietnam veterans. Dohrenwend et al. (2006) confirmed this suspicion. Dohrenwend et al.'s reanalysis of the NVVRS data resulted in a prevalence estimate 40% lower than the original NVVRS estimate. Furthermore, had they required clinically significant functional impairment, the prevalence rate would have been 65% lower than the original NVVRS rate. That is, the current (late 1980s) prevalence estimates for PTSD are 15.2% (original NVVRS), 9.1% (Dohrenwend et al.), and 5.4% (clinically significant functional impairment). The policy implications of these findings are discussed.}, } @article {pmid17703798, year = {2007}, author = {Moser, L}, title = {The effects of music therapy on pain.}, journal = {Kentucky nurse}, volume = {55}, number = {3}, pages = {10}, pmid = {17703798}, issn = {0742-8367}, mesh = {Coronary Angiography/adverse effects ; Humans ; *Music Therapy ; Pain/etiology ; *Pain Management ; }, abstract = {The findings of Bally et al.'s (2003) study failed to support the use of music therapy to decrease pain. Therefore, this research cannot be used in the group research utilization project to teach nurses the effects of music on lessening pain. A feasibility issue for teaching nurses on the effects of music would be the large sum of money it would take to educate the nurses and purchase the music and stereo equipment needed. Future research suggestions would be to include additional research participants, and to study more than two separate procedures, which are more invasive.}, } @article {pmid17698372, year = {2007}, author = {Vogt, S and Buccino, G and Wohlschläger, AM and Canessa, N and Shah, NJ and Zilles, K and Eickhoff, SB and Freund, HJ and Rizzolatti, G and Fink, GR}, title = {Prefrontal involvement in imitation learning of hand actions: effects of practice and expertise.}, journal = {NeuroImage}, volume = {37}, number = {4}, pages = {1371-1383}, doi = {10.1016/j.neuroimage.2007.07.005}, pmid = {17698372}, issn = {1053-8119}, mesh = {Adult ; Brain Mapping ; Echo-Planar Imaging ; Female ; Hand/*physiology ; Humans ; Image Processing, Computer-Assisted ; Learning/*physiology ; Linear Models ; Magnetic Resonance Imaging ; Male ; Motor Skills/physiology ; Music ; Neurons/physiology ; *Practice, Psychological ; Prefrontal Cortex/*physiology ; Psychomotor Performance/*physiology ; }, abstract = {In this event-related fMRI study, we demonstrate the effects of a single session of practising configural hand actions (guitar chords) on cortical activations during observation, motor preparation and imitative execution. During the observation of non-practised actions, the mirror neuron system (MNS), consisting of inferior parietal and ventral premotor areas, was more strongly activated than for the practised actions. This finding indicates a strong role of the MNS in the early stages of imitation learning. In addition, the left dorsolateral prefrontal cortex (DLPFC) was selectively involved during observation and motor preparation of the non-practised chords. This finding confirms Buccino et al.'s [Buccino, G., Vogt, S., Ritzl, A., Fink, G.R., Zilles, K., Freund, H.-J., Rizzolatti, G., 2004a. Neural circuits underlying imitation learning of hand actions: an event-related fMRI study. Neuron 42, 323-334] model of imitation learning: for actions that are not yet part of the observer's motor repertoire, DLPFC engages in operations of selection and combination of existing, elementary representations in the MNS. The pattern of prefrontal activations further supports Shallice's [Shallice, T., 2004. The fractionation of supervisory control. In: Gazzaniga, M.S. (Ed.), The Cognitive Neurosciences, Third edition. MIT Press, Cambridge, MA, pp. 943-956] proposal of a dominant role of the left DLPFC in modulating lower level systems and of a dominant role of the right DLPFC in monitoring operations.}, } @article {pmid17688089, year = {2007}, author = {Tomás-Sábado, J and Limonero, JT}, title = {Death depression and death obsession: are they different constructs?.}, journal = {Psychological reports}, volume = {100}, number = {3 Pt 1}, pages = {755-758}, doi = {10.2466/pr0.100.3.755-758}, pmid = {17688089}, issn = {0033-2941}, mesh = {Adolescent ; Adult ; *Attitude to Death ; Depression/*psychology ; Female ; Humans ; Male ; Obsessive Behavior/*psychology ; Reproducibility of Results ; Surveys and Questionnaires ; }, abstract = {This study examined the dimensional structure of Templer, et al.'s Death Depression Scale-Revised and Abdel-Khalek's Death Obsession Scale. The responses of 353 Spanish undergraduates, 261 women and 92 men (M age= 19 yr., SD= 3.1), to the Spanish forms of both scales were evaluated by means of a principal axis factoring with oblimin rotation. Three significant factors were identified: (1) Death Sadness, (2) Death Obsession, and (3) Death Anergia and Anhedonia. The distribution of the factor loadings for the items of both scales supported discriminant validity and capacity to evaluate aspects of human reactions to death.}, } @article {pmid17681127, year = {2007}, author = {Kalverda, B and Fornerod, M}, title = {The nuclear life of nucleoporins.}, journal = {Developmental cell}, volume = {13}, number = {2}, pages = {164-165}, doi = {10.1016/j.devcel.2007.07.008}, pmid = {17681127}, issn = {1534-5807}, mesh = {Cell Nucleus/*metabolism ; Homeodomain Proteins/metabolism ; Models, Biological ; Nuclear Pore Complex Proteins/chemistry/*metabolism ; Repetitive Sequences, Amino Acid ; Saccharomyces cerevisiae/metabolism ; Transcription, Genetic ; }, abstract = {Nucleoporins are the constituents of the nuclear pore complex, but they are also known to shuttle to the nuclear interior, the function of which is unclear. In a recent issue of Nature Cell Biology, Wang et al.'s mechanistic studies of leukemogenic fusion proteins that contain nucleoporins suggest that they have a direct role in transcription.}, } @article {pmid17670105, year = {2003}, author = {Opfermann, UT and Doll, N and Walther, T and Mohr, FW}, title = {Combined mitral valve repair, LVOT myectomy and left atrial cryoablation therapy.}, journal = {Interactive cardiovascular and thoracic surgery}, volume = {2}, number = {4}, pages = {501-502}, doi = {10.1016/S1569-9293(03)00129-4}, pmid = {17670105}, issn = {1569-9285}, abstract = {Asymmetric septal hypertrophy (ASH) is a common cause of left ventricular (LV) outflow tract obstruction. Mitral valve (MV) regurgitation is present in 30% of those patients as well as biatrial enlargement. Furthermore, paroxysmal or chronic atrial fibrillation (AF) occurs in up to 22%. Two male patients were admitted for shortness of breath and decreased physical ability. Hypertrophic obstructive cardiomyopathy (HOCM) with ASH, severe MV regurgitation and chronic AF were diagnosed in both patients; present for 8 years in patient 1 and 1 year in patient 2. Both received MV annuloplasty, transaortic septal resection using the modified Morrow et al.'s technique and left atrial cryoablation therapy via median sternotomy. Intraoperative measurement revealed no residual gradients and competent MV, furthermore, both patients were discharged in sinus rhythm.}, } @article {pmid17659321, year = {2007}, author = {Weerasooriya, R and Tobschall, HJ and Bandara, A}, title = {Modeling interactions of Hg(II) and bauxitic soils.}, journal = {Chemosphere}, volume = {69}, number = {10}, pages = {1525-1532}, doi = {10.1016/j.chemosphere.2007.05.091}, pmid = {17659321}, issn = {0045-6535}, mesh = {Adsorption ; Aluminum Oxide/*analysis ; Kinetics ; Mercury Compounds/*chemistry ; *Models, Chemical ; Soil/*analysis/standards ; Soil Pollutants/*chemistry ; }, abstract = {The adsorptive interactions of Hg(II) with gibbsite-rich soils (hereafter SOIL-g) were modeled by 1-pK surface complexation theory using charge distribution multi-site ion competition model (CD MUSIC) incorporating basic Stern layer model (BSM) to account for electrostatic effects. The model calibrations were performed for the experimental data of synthetic gibbsite-Hg(II) adsorption. When [NaNO(3)] > or = 0.01M, the Hg(II) adsorption density values, of gibbsite, Gamma(Hg(II)), showed a negligible variation with ionic strength. However, Gamma(Hg(II)) values show a marked variation with the [Cl(-)]. When [Cl(-)] > or = 0.01M, the Gamma(Hg(II)) values showed a significant reduction with the pH. The Hg(II) adsorption behavior in NaNO(3) was modeled assuming homogeneous solid surface. The introduction of high affinity sites, i.e., >Al(s)OH at a low concentration (typically about 0.045 sites nm(-2)) is required to model Hg(II) adsorption in NaCl. According to IR spectroscopic data, the bauxitic soil (SOIL-g) is characterized by gibbsite and bayerite. These mineral phases were not treated discretely in modeling of Hg(II) and soil interactions. The CD MUSIC/BSM model combination can be used to model Hg(II) adsorption on bauxitic soil. The role of organic matter seems to play a role on Hg(II) binding when pH>8. The Hg(II) adsorption in the presence of excess Cl(-) ions required the selection of high affinity sites in modeling.}, } @article {pmid17640722, year = {2007}, author = {de Vries, H}, title = {Comment on "Modifiable family and school environmental factors associated with smoking status among adolescents in Guangzhou, China".}, journal = {Preventive medicine}, volume = {45}, number = {2-3}, pages = {119-120}, doi = {10.1016/j.ypmed.2007.04.014}, pmid = {17640722}, issn = {0091-7435}, mesh = {Adolescent ; China/epidemiology ; *Family Characteristics ; Humans ; *Schools ; Smoking/*epidemiology ; Smoking Prevention ; }, abstract = {Chen and colleagues describe social factors that are related with Chinese adolescent smoking behaviors [Chen, W., Wen, X., Muscat, J., et al., 2007-this issue. Modifiable family and school environmental factors associated with smoking status among adolescents in Guangzhou, China. Prev. Med. doi:10.1016/j.ypmed.2007.02.009]. These types of studies in China are very much needed given the fact that smoking is a significant health problem in China. Environmental factors may be more important than sometimes thought, since some studies suggest that smoking onset may not be such a 'reasoned' process by youngsters (Kremers, S.P., Mudde, A.N., de Vries, N.K., Brug, J., de Vries, H., 2004. Unplanned smoking initiation: new insights and implications for interventions. Patient Educ. Couns. 55 (3), 345-52.). Studies indicate that a multitude of factors are related to smoking onset, and thus deserve attention in a smoking prevention approach (see, e.g., [Tyas, S., Pederson, L., 1998. Psychosocial factors related to adolescent smoking: a critical review of the literature. Tob. Control 7, 409-420; Lantz, P., Jacobson, P., Warner, K., et al., 2000. Investing in youth tobacco control: a review of smoking prevention and control strategies. Tob. Control 9, 47-63]). The study conclusions were derived from a cross-sectional report. Consequently, one needs to be careful in making conclusions about causal pathways [Bauman, K., Fisher, L., 1986. On the measurement of friend behavior in research on friend influence and selection: findings from longitudinal studies of adolescent smoking and drinking. J. Youth Adolesc. 15 (4), 345-353]. Longitudinal studies also suggest the impact of selection mechanisms implying that adolescents were not pressured to start to smoke, but selected smoking friends. Chen, W., Wen, X., Muscat, J., et al.'s [2007-this issue. Modifiable family and school environmental factors associated with smoking status among adolescents in Guangzhou, China. Prev. Med. doi:10.1016/j.ypmed.2007.02.009.] work is important because it describes one of the many steps that are needed in China for realizing effective smoking prevention programs, a study that could be described as one of the first steps in the planning cycle of health promotion [Green, L., Kreuter, M., 1999. Health Promotion Planning: An Educational and Ecological Approach. Mayfield Publishing Company, Mountain View, CA]. Ultimately Chen and colleagues may want to develop smoking prevention interventions. These interventions should indeed incorporate the modifiable social factors, and - as the Chinese data suggest - should be gender sensitive. Consequently, the great challenge for Chen and several other Chinese colleagues will be to develop an integral long-term approach for their country to prevent smoking onset as effectively as possible using comprehensive approaches.}, } @article {pmid17638290, year = {2007}, author = {Khondoker, MR and Glasbey, CA and Worton, BJ}, title = {A comparison of parametric and nonparametric methods for normalising cDNA microarray data.}, journal = {Biometrical journal. Biometrische Zeitschrift}, volume = {49}, number = {6}, pages = {815-823}, doi = {10.1002/bimj.200610338}, pmid = {17638290}, issn = {1521-4036}, mesh = {Anemia, Iron-Deficiency/genetics ; Animals ; Computer Simulation ; *Data Interpretation, Statistical ; Female ; Kidney/physiology ; Liver/pathology/physiology ; *Models, Statistical ; Oligonucleotide Array Sequence Analysis/*methods ; Rats ; *Statistics, Nonparametric ; }, abstract = {Normalisation is an essential first step in the analysis of most cDNA microarray data, to correct for effects arising from imperfections in the technology. Loess smoothing is commonly used to correct for trends in log-ratio data. However, parametric models, such as the additive plus multiplicative variance model, have been preferred for scale normalisation, though the variance structure of microarray data may be of a more complex nature than can be accommodated by a parametric model. We propose a new nonparametric approach that incorporates location and scale normalisation simultaneously using a Generalised Additive Model for Location, Scale and Shape (GAMLSS, Rigby and Stasinopoulos, 2005, Applied Statistics, 54, 507-554). We compare its performance in inferring differential expression with Huber et al.'s (2002, Bioinformatics, 18, 96-104) arsinh variance stabilising transformation (AVST) using real and simulated data. We show GAMLSS to be as powerful as AVST when the parametric model is correct, and more powerful when the model is wrong.}, } @article {pmid17614264, year = {2007}, author = {Sadegh-Zadeh, K}, title = {The fuzzy polynucleotide space revisited.}, journal = {Artificial intelligence in medicine}, volume = {41}, number = {1}, pages = {69-80; discussion 81-2}, doi = {10.1016/j.artmed.2007.04.006}, pmid = {17614264}, issn = {0933-3657}, mesh = {*Base Sequence ; *Fuzzy Logic ; Humans ; Models, Genetic ; *Nucleic Acid Conformation ; *Polynucleotides ; }, abstract = {OBJECTIVE: A theory of fuzzy polynucleotides, including an n-dimensional metric fuzzy polynucleotide space, has been previously introduced by the present author for fuzzy-theoretical analysis of nucleic acids [Sadegh-Zadeh K. Fuzzy genomes. Artif Intell Med 2000;18:1-28; Sadegh-Zadeh K. Ein Verfahren zur Fuzzydecodierung und Fuzzydechiffrierung von Informationen. Offenlegungsschrift DE 199 36 925 A 1. Deutsches Patent- und Markenamt; 2001]. The conceptual framework of that theory has been used by Nieto et al. [Nieto JJ, Torres A, Vázquez-Trasande MM. A metric space to study differences between polynucleotides. Appl Math Lett 2003;16:1289-94; Nieto JJ, Torres A, Georgiou DN, Karakasidis TE. Fuzzy polynucleotide spaces and metrics. Bull Math Biol 2006;68:703-25] and Torres et al. [Torres A, Nieto JJ. The fuzzy polynucleotide space: basic properties. Bioinformatics 2003;19:587-92; Torres A, Nieto JJ. Fuzzy logic in medicine and bioinformatics. J Biomed Biotechnol 2006;1-7 [Article ID 91908]] to create a completely different, 12-dimensional metric space which they have also called 'the fuzzy polynucleotide space'. In the present paper both spaces are compared.

MATERIAL AND METHOD: Both metric spaces are briefly outlined. Similarity and dissimilarity relationships between polynucleotide strings are measured in both spaces to compare their performance.

RESULTS: Nieto et al.'s and Torres et al.'s metric space measures the relationships between polynucleotide chains incorrectly. Structurally highly different polynucleotide sequences are misclassified as highly similar ones, and completely different sequences are misclassified as identical ones. For this reason their construct is to be considered as a device of misdiagnosis that bears "fuzzy polynucleotide space" as a misnomer.}, } @article {pmid17600578, year = {2007}, author = {Zhang, Y and Benson, DA and Baeumer, B}, title = {Predicting the tails of breakthrough curves in regional-scale alluvial systems.}, journal = {Ground water}, volume = {45}, number = {4}, pages = {473-484}, doi = {10.1111/j.1745-6584.2007.00320.x}, pmid = {17600578}, issn = {0017-467X}, mesh = {Fresh Water/analysis ; *Models, Theoretical ; Monte Carlo Method ; *Water Movements ; }, abstract = {The late tail of the breakthrough curve (BTC) of a conservative tracer in a regional-scale alluvial system is explored using Monte Carlo simulations. The ensemble numerical BTC, for an instantaneous point source injected into the mobile domain, has a heavy late tail transforming from power law to exponential due to a maximum thickness of clayey material. Haggerty et al.'s (2000) multiple-rate mass transfer (MRMT) method is used to predict the numerical late-time BTCs for solutes in the mobile phase. We use a simple analysis of the thicknesses of fine-grained units noted in boring logs to construct the memory function that describes the slow decline of concentrations at very late time. The good fit between the predictions and the numerical results indicates that the late-time BTC can be approximated by a summation of a small number of exponential functions, and its shape depends primarily on the thicknesses and the associated volume fractions of immobile water in "blocks" of fine-grained material. The prediction of the late-time BTC using the MRMT method relies on an estimate of the average advective residence time, t(ad). The predictions are not sensitive to estimation errors in t(ad), which can be approximated by L/v , where v is the arithmetic mean ground water velocity and L is the transport distance. This is the first example of deriving an analytical MRMT model from measured hydrofacies properties to predict the late-time BTC. The parsimonious model directly and quantitatively relates the observable subsurface heterogeneity to nonlocal transport parameters.}, } @article {pmid17598149, year = {2007}, author = {Barry, C and Burgess, N}, title = {Learning in a geometric model of place cell firing.}, journal = {Hippocampus}, volume = {17}, number = {9}, pages = {786-800}, doi = {10.1002/hipo.20324}, pmid = {17598149}, issn = {1050-9631}, support = {G0501672/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Action Potentials/*physiology ; Animals ; Behavior, Animal ; Hippocampus/cytology ; *Learning ; *Models, Neurological ; Neurons/*physiology ; Space Perception/*physiology ; }, abstract = {Following Hartley et al. (Hartley et al. (2000) Hippocampus 10:369-379), we present a simple feed-forward model of place cell (PC) firing predicated on neocortical information regarding the environmental geometry surrounding the animal. Incorporating the idea of boundaries with distinct sensory qualities, we show that synaptic plasticity mediated by a BCM-like rule (Bienenstock et al. (1982) J Neurosci 2:32-48) produces PCs that encode position relative to specific extended landmarks. In an unchanging environment the model is shown to undergo an initial phase of learning, resulting in the formation of stable place fields. In familiar environments, perturbation of environmental cues produces graded changes in the firing rate and position of place fields. Model simulations are compared favorably with three sets of experimental data: (1) Results published by Barry et al. (Barry et al. (2006) Rev Neurosci 17:71-97) showing the slow disappearance of duplicate place fields produced when a barrier is placed into a familiar environment. (2) Rivard et al.'s (Rivard et al. (2004) J Gen Physiol 124:9-25) study showing a graded response in PC firing such that fields near to a centrally placed object encode space relative to the object, whereas more distant fields respond to the surrounding environment. (3) Fenton et al.'s (Fenton et al. (2000a) J Gen Physiol 116:191-209) observation that inconsistent rotation of cue cards produces parametric changes in place field positions. The merits of the model are discussed in terms of its extensibility and biological plausibility.}, } @article {pmid17569408, year = {2007}, author = {Song, LY}, title = {The attitudes towards and enactment of psychosocial rehabilitation principles: discrepancies and correlates.}, journal = {The International journal of social psychiatry}, volume = {53}, number = {3}, pages = {232-246}, doi = {10.1177/0020764006074558}, pmid = {17569408}, issn = {0020-7640}, mesh = {Adult ; *Attitude of Health Personnel ; Female ; Humans ; Male ; *Psychology ; Rehabilitation/*psychology ; Surveys and Questionnaires ; Taiwan ; }, abstract = {BACKGROUND: Previous literature suggests that attitudes have critical effects on recovery outcomes. Yet mental health professionals' attitudes towards psychiatric rehabilitation principles (PRP) have not been fully addressed. Whether the professionals could act in accordance with attitudes has also not been examined.

AIMS: This study explored how hospital professionals in Taiwan perceived PRP, and whether there were discrepancies between attitudes towards and enactment of PRP. Also, the correlates of attitudes and enactment were examined.

METHODS: Survey questionnaires were sent to hospitals in Taiwan, and yielded a valid sample of 743 subjects, with a 23.48% return rate. The potential correlates included five groups of variables: demographic, professional background, training experience, and external and internal structure of hospital.

RESULTS: The factor analyses revealed nine factors of PRP, which partly confirmed Cnaan et al.'s findings (1990), and added recovery components. Hospital professionals held favorable attitudes toward and enacted more on recovery and strengths perspectives, yet less on social change, commitment from staff, and using environmental resources. The discrepancies between attitudes and enactment were mainly on macro related principles. Attitudes and hospital emphasis on psychiatric rehabilitation (PR) in discharge plans were the two most important correlates of enactment.

CONCLUSIONS: Doctors are the training target group for enhancing favorable attitudes and enactment. Continuous advocacies on structural changes for increasing PR resources, and hospital emphasis on PR in treatment approach are needed.}, } @article {pmid17563845, year = {2007}, author = {Lanza, C and Bolli, V and Galeazzi, V and Fabrizzi, B and Fabrizzi, G}, title = {Cystic adenomatoid malformation in children: CT histopathological correlation.}, journal = {La Radiologia medica}, volume = {112}, number = {4}, pages = {612-619}, pmid = {17563845}, issn = {0033-8362}, mesh = {Child ; Child, Preschool ; Cystic Adenomatoid Malformation of Lung, Congenital/*diagnostic imaging/*pathology ; Female ; Humans ; Infant ; Infant, Newborn ; Male ; Reproducibility of Results ; Retrospective Studies ; *Tomography, X-Ray Computed ; }, abstract = {PURPOSE: This study was performed to assess the accuracy of computed tomography (CT) in classifying the various types of cystic adenomatoid malformation (CAM) of the lung, as described by Stocker et al., taking histopathology as the gold standard.

MATERIALS AND METHODS: We retrospectively reviewed six cases of histologically proven CAM. Chest radiography, chest CT and histopathology results were available for all patients. The CT images were reviewed blinded to the histological findings, and attention was paid to the number and size of cysts so as to classify the lesions into the three groups described by Stocker et al. The classification of lesions based on the CT images was then correlated to the histopathological findings.

RESULTS: Areas with small-sized cysts (<2 cm) were detected by CT in two patients (33.3%), areas with large cysts (>2 cm) were seen in three cases (50%) whereas in the remaining case, the diagnosis was mixed type I and type II CAM. In one patient with type I CAM, an area of low-density consolidation around the cysts was interpreted as CAM in a context of pulmonary sequestration. The CT classification based on Stocker et al.'s categories was in agreement with the histopathological findings in four cases, whereas in the remaining two cases, the lesions were classed as type I or II on CT and as mixed (type I and II) lesions at histopathology. In one case, the CT classification was correct, but the histopathology revealed the coexistence of pulmonary sequestration.

CONCLUSIONS: In our study, there was concordance between CT and histopathology in 66.7% of cases, whereas in 33.3% histopathology revealed areas with mixed grade lesions. CT proved to be accurate in identifying and characterising CAM and provided important information on lesion site and extension.}, } @article {pmid17563206, year = {2007}, author = {Ruscio, J and Marcus, DK}, title = {Detecting small taxa using simulated comparison data: A reanalysis of Beach, Amir, and Bau's (2005) data.}, journal = {Psychological assessment}, volume = {19}, number = {2}, pages = {241-246}, doi = {10.1037/1040-3590.19.2.241}, pmid = {17563206}, issn = {1040-3590}, mesh = {Algorithms ; *Computer Simulation ; Humans ; Mathematical Computing ; Personality Assessment/*statistics & numerical data ; Personality Inventory/*statistics & numerical data ; Psychometrics/*statistics & numerical data ; }, abstract = {On the basis of taxometric analyses of data sets that they created to pose interpretive challenges, S. R. H. Beach, N. Amir, and J. J. Bau (2005) cautioned that using comparison data simulated by J. Ruscio's programs can lead to inaccurate conclusions. Careful examination of S. R. H. Beach et al.'s methods and results plus reanalysis of their data fails to substantiate this concern: Using comparison data identified the taxonic structure of S. R. H. Beach et al.'s data sets, even when the taxon base rate was very low. The authors show that J. Ruscio's simulation programs generate comparison data appropriately and that analyzing these data provides a useful interpretive aid. Additionally, the authors discuss and illustrate the effective use of the inchworm consistency test to disambiguate taxometric results for small taxa and dimensional constructs with positively skewed indicators.}, } @article {pmid17562472, year = {2007}, author = {Goloboff, PA and Pol, D}, title = {On divide-and-conquer strategies for parsimony analysis of large data sets: Rec-I-DCM3 versus TNT.}, journal = {Systematic biology}, volume = {56}, number = {3}, pages = {485-495}, doi = {10.1080/10635150701431905}, pmid = {17562472}, issn = {1063-5157}, mesh = {*Algorithms ; Classification/*methods ; Computational Biology/*methods ; Software ; Time Factors ; }, abstract = {Roshan et al. recently described a "divide-and-conquer" technique for parsimony analysis of large data sets, Rec-I-DCM3, and stated that it compares very favorably to results using the program TNT. Their technique is based on selecting subsets of taxa to create reduced data sets or subproblems, finding most-parsimonious trees for each reduced data set, recombining all parts together, and then performing global TBR swapping on the combined tree. Here, we contrast this approach to sectorial searches, a divide-and-conquer algorithm implemented in TNT. This algorithm also uses a guide tree to create subproblems, with the first-pass state sets of the nodes that join the selected sectors with the rest of the topology; this allows exact length calculations for the entire topology (that is, any solution N steps shorter than the original, for the reduced subproblem, must also be N steps shorter for the entire topology). We show here that, for sectors of similar size analyzed with the same search algorithms, subdividing data sets with sectorial searches produces better results than subdividing with Rec-I-DCM3. Roshan et al.'s claim that Rec-I-DCM3 outperforms the techniques in TNT was caused by a poor experimental design and algorithmic settings used for the runs in TNT. In particular, for finding trees at or very close to the minimum known length of the analyzed data sets, TNT clearly outperforms Rec-I-DCM3. Finally, we show that the performance of Rec-I-DCM3 is bound by the efficiency of TBR implementation for the complete data set, as this method behaves (after some number of iterations) as a technique for cyclic perturbations and improvements more than as a divide-and-conquer strategy.}, } @article {pmid17543439, year = {2007}, author = {Hsueh, CH and Thompson, GA}, title = {Appraisal of formulas for stresses in bilayered dental ceramics subjected to biaxial moment loading.}, journal = {Journal of dentistry}, volume = {35}, number = {7}, pages = {600-606}, doi = {10.1016/j.jdent.2007.04.004}, pmid = {17543439}, issn = {0300-5712}, mesh = {Ceramics/*chemistry ; Dental Stress Analysis/*methods ; Finite Element Analysis ; Models, Theoretical ; Pliability ; Weight-Bearing ; }, abstract = {OBJECTIVES: The purpose of this study was to compare three existing sets of formulas predicting stresses in a thin circular plate subjected to biaxial moment loading, such that limitations for each set of formulas could be understood. These formulas include American Society for Testing and Materials (ASTM) formulas for monolayered plates, Roark's formulas for bilayered plates, and Hsueh et al.'s formulas for multilayered plates.

METHODS: The three sets of formulas were summarized and appraised. Biaxial moment loading is generally achieved using biaxial flexure tests, and the plate is placed on a support ring and loaded in the central region. While both ASTM and Hsueh et al.'s formulas predict stresses through the thickness of the plate, Roark's formulas predict stresses only on the top and the bottom surfaces of the plate. Also, a simply supported plate at its edge is considered in Roark's formulas. We modified Roark's formulas to include the overhang region of the plate to more closely simulate the actual loading configuration. Then, the accuracy of formulas was examined by comparing with finite element results of monolayered and bilayered plates subjected to ring-on-ring loading.

RESULTS: Monolayer is a special case of bilayer, and both monolayer and bilayer are special cases of multilayer. For monolayered plates, ASTM and Hsueh et al.'s formulas are identical, and both are in excellent agreement with finite element results. For bilayered plates, Hsueh et al.'s formulas are in excellent agreement with finite element results. For both monolayered and bilayered plates, Roark's formulas deviate from finite element results while the modified Roark's formulas are accurate.

CONCLUSIONS: Roark's formulas for evaluating the biaxial strength of bilayered dental ceramics will result in errors in predicted stresses which depend on the size of the overhang region of the plate in the actual loading configuration. Also, Roark's formulas are limited to predicting stresses on the top and the bottom surfaces of the plate. On the other hand, Hsueh et al.'s formulas are for multilayered plates and predict stresses through the plate thickness.}, } @article {pmid17534575, year = {2007}, author = {Bertrand, M and Slater, GW}, title = {Tethered polyelectrolytes under the action of an electrical field: a molecular-dynamics study.}, journal = {The European physical journal. E, Soft matter}, volume = {23}, number = {1}, pages = {83-89}, pmid = {17534575}, issn = {1292-8941}, support = {R01 HG002918-01/HG/NHGRI NIH HHS/United States ; }, mesh = {Chemistry, Physical/methods ; DNA/chemistry ; Electrochemistry/methods ; Electrolytes/*chemistry ; Electrophoresis ; Models, Chemical ; Models, Statistical ; Molecular Conformation ; Surface Properties ; }, abstract = {For a polyelectrolyte undergoing electrophoretic motion, it is predicted (D. Long, J.L. Viovy, A. Ajdari, Phys. Rev. Lett. 76, 3858 (1996); D. Long, A. Ajdari, Electrophoresis 17, 1161 (1996)) that the mechanical force necessary to stall the molecule is substantially smaller than the sum of electrical forces applied on all monomers. In fact, it should be proportional to its hydrodynamic friction coefficient and therefore to the size of its conformation. In our work we examine this prediction using coarse-grained molecular-dynamics simulations in which we explicitly include the polymer, the solvent, the counterions and salt. The electrophoretic mobility of polyelectrolytes is evaluated, the mechanical force necessary to keep the molecules tethered is measured and the resulting anisotropic polymer conformations are observed and quantified. Our results corroborate Long et al.'s prediction.}, } @article {pmid17521994, year = {2000}, author = {Whittenburg, JA and Tice, PP and Baker, G and Lemmey, DE}, title = {A critical appraisal of the 1998 meta-analytic review of child sexual abuse outcomes reported by rind, tromovitch, and bauserman.}, journal = {Journal of child sexual abuse}, volume = {9}, number = {3-4}, pages = {135-155}, doi = {10.1300/j070v09n03_07}, pmid = {17521994}, issn = {1053-8712}, abstract = {The goal of this article is to present a methodological critique of the 1998 meta-analysis of child sexual abuse outcomes by Rind, Tromovitch, and Bauserman. Seven major concerns are addressed. Rind et al.'s view is, at best, extremely limited. By restricting a supposedly broad meta-analysis to only some of the population in question, the conclusions they drew regarding this complex topic, primarily that adult-child sex is not necessarily harmful, are invalid.}, } @article {pmid17505656, year = {2007}, author = {Biondo-Simões, Mde L and Castro, GR and Montibeller, GR and Sadowski, JA and Biondo-Simões, R}, title = {The influence of hypothyroidism on liver regeneration: an experimental study in rats.}, journal = {Acta cirurgica brasileira}, volume = {22 Suppl 1}, number = {}, pages = {52-56}, doi = {10.1590/s0102-86502007000700011}, pmid = {17505656}, issn = {0102-8650}, mesh = {Animals ; Disease Models, Animal ; Hepatectomy ; Hypothyroidism/*physiopathology ; Liver/*physiology ; Liver Regeneration/*physiology ; Male ; Proliferating Cell Nuclear Antigen/analysis ; Rats ; Rats, Wistar ; Thyroidectomy ; }, abstract = {BACKGROUND: The influence of hypothyroidism in liver regeneration has been a controversial opinions.

PURPOSE: The aim of this study is to identify the relationship between hypothyroidism and liver regeneration in rats.

METHODS: Forty male Wistar rats divided into two groups of 20 specimens each. One group (C) consisted of euthyroid rats, and the other (H) of hypothyroid rats. All the animals were anesthetized with xylazine and ketamine and subjected to a longitudinal incision in the anterior cervical region. The thyroid was completely resected in group H and left intact in group C. Ten days after the first surgery, both groups of rats were weighed and submitted to partial hepatectomy, in which the left lateral and median lobes were resected and weighed. Examinations were carried out after 24 hours and, on day 7, using 3 methods: KWON et al.'s formula to identify increase in volume; mitotic figure count in five fields; and the percentage of PCNA-positive nuclei in five fields.

RESULTS: Using KWON's formula, the regeneration rate for Group C after 24 hours was 58.49% whereas that for Group H was 50.42% (p=0.0165). After 7 days, the regeneration rate for Group C was 93.04% and Group H 93.74% (p=0.2165). The average number of mitotic figures after 24 hours was 14 +/- 1.5 for Group C and 9.8 +/- 2.2 for Group H (p=0,00016). After 7 days the corresponding figures were 5.4 +/-1.1 and 5.1+/- 1.2 (p=0,6343). The average number of PCNA-positive nuclei after 24 hours was 13.55+/- 3.84 in Group C and 7.7 +/- 2.11 in Group H (p =0,0006)). The corresponding figures after 7 days were 3.5 +/- 2.39 for Group C and 4.11 +/-1.90 for Group H (p>0.05).

CONCLUSION: We conclude that hypothyroidism in rats causes a delay in hepatic regeneration in the first 24 hours, but that after seven days the rate of regeneration is equal to that in euthyroid rats.}, } @article {pmid17500637, year = {2007}, author = {Anderson, BL}, title = {The demise of the identity hypothesis and the insufficiency and nonnecessity of contour relatability in predicting object interpolation: comment on Kellman, Garrigan, and Shipley (2005).}, journal = {Psychological review}, volume = {114}, number = {2}, pages = {470-487}, doi = {10.1037/0033-295X.114.2.470}, pmid = {17500637}, issn = {0033-295X}, mesh = {*Depth Perception ; *Form Perception ; Humans ; Logic ; *Models, Psychological ; Pattern Recognition, Visual ; }, abstract = {P. J. Kellman, P. Garrigan, and T. F. Shipley's theory of 3-dimensional object interpolation asserts that existing data, as well as logical considerations, support the view that an identical contour interpolation process underlies the interpolation of partially camouflaged and partially occluded objects (modal completion and amodal completion, respectively). Here, the author argues that recent data show that this theory is incorrect and that the logical arguments offered in support of the identity hypothesis depend on specific unverified models of the phenomena in question. Alternative explanations of these effects are developed to show that such phenomena do not logically implicate an identity hypothesis and, in some cases, provide strong evidence against the identity hypothesis. Finally, the author describes several completion phenomena that reveal that the relatability criteria embodied in Kellman et al.'s model are neither necessary nor sufficient for understanding the interpolation processes the model was designed to explain.}, } @article {pmid17496375, year = {2007}, author = {Werner, T}, title = {A linear programming approach to max-sum problem: a review.}, journal = {IEEE transactions on pattern analysis and machine intelligence}, volume = {29}, number = {7}, pages = {1165-1179}, doi = {10.1109/TPAMI.2007.1036}, pmid = {17496375}, issn = {0162-8828}, mesh = {*Algorithms ; *Artificial Intelligence ; Game Theory ; Image Enhancement/*methods ; Image Interpretation, Computer-Assisted/*methods ; Imaging, Three-Dimensional/*methods ; Pattern Recognition, Automated/*methods ; Programming, Linear ; }, abstract = {The max-sum labeling problem, defined as maximizing a sum of binary (i.e., pairwise) functions of discrete variables, is a general NP-hard optimization problem with many applications, such as computing the MAP configuration of a Markov random field. We review a not widely known approach to the problem, developed by Ukrainian researchers Schlesinger et al. in 1976, and show how it contributes to recent results, most importantly, those on the convex combination of trees and tree-reweighted max-product. In particular, we review Schlesinger et al.'s upper bound on the max-sum criterion, its minimization by equivalent transformations, its relation to the constraint satisfaction problem, the fact that this minimization is dual to a linear programming relaxation of the original problem, and the three kinds of consistency necessary for optimality of the upper bound. We revisit problems with Boolean variables and supermodular problems. We describe two algorithms for decreasing the upper bound. We present an example application for structural image analysis.}, } @article {pmid17481919, year = {2007}, author = {Mitchell, RL}, title = {fMRI delineation of working memory for emotional prosody in the brain: commonalities with the lexico-semantic emotion network.}, journal = {NeuroImage}, volume = {36}, number = {3}, pages = {1015-1025}, doi = {10.1016/j.neuroimage.2007.03.016}, pmid = {17481919}, issn = {1053-8119}, mesh = {Adult ; Brain/*physiology ; Emotions/*physiology ; Female ; Functional Laterality/physiology ; Humans ; Image Processing, Computer-Assisted ; *Language ; Magnetic Resonance Imaging ; Male ; Memory, Short-Term/*physiology ; Nerve Net/*physiology ; Oxygen/blood ; *Semantics ; Sex Characteristics ; }, abstract = {Decoding emotional prosody is crucial for successful social interactions, and continuous monitoring of emotional intent via prosody requires working memory. It has been proposed by Ross and others that emotional prosody cognitions in the right hemisphere are organized in an analogous fashion to propositional language functions in the left hemisphere. This study aimed to test the applicability of this model in the context of prefrontal cortex working memory functions. BOLD response data were therefore collected during performance of two emotional working memory tasks by participants undergoing fMRI. In the prosody task, participants identified the emotion conveyed in pre-recorded sentences, and working memory load was manipulated in the style of an N-back task. In the matched lexico-semantic task, participants identified the emotion conveyed by sentence content. Block-design neuroimaging data were analyzed parametrically with SPM5. At first, working memory for emotional prosody appeared to be right-lateralized in the PFC, however, further analyses revealed that it shared much bilateral prefrontal functional neuroanatomy with working memory for lexico-semantic emotion. Supplementary separate analyses of males and females suggested that these language functions were less bilateral in females, but their inclusion did not alter the direction of laterality. It is concluded that Ross et al.'s model is not applicable to prefrontal cortex working memory functions, that evidence that working memory cannot be subdivided in prefrontal cortex according to material type is increased, and that incidental working memory demands may explain the frontal lobe involvement in emotional prosody comprehension as revealed by neuroimaging studies.}, } @article {pmid17477541, year = {2007}, author = {Davis, F and Terry, LA and Chope, GA and Faul, CF}, title = {Effect of extraction procedure on measured sugar concentrations in onion (Allium cepa L.) bulbs.}, journal = {Journal of agricultural and food chemistry}, volume = {55}, number = {11}, pages = {4299-4306}, doi = {10.1021/jf063170p}, pmid = {17477541}, issn = {0021-8561}, mesh = {Carbohydrates/*analysis/isolation & purification ; Chromatography, High Pressure Liquid ; Fructans/analysis ; Fructose/analysis ; Glucose/analysis ; Onions/*chemistry ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; Sucrose/analysis ; }, abstract = {Bulb samples from a range of onion cultivars grown over three consecutive years were freeze-dried and the resulting powders extracted using three previously reported methods. The extracts were analyzed for fructose, glucose, and sucrose content using HPLC coupled with ELSD, and for fructans using MALDI-MS. The three methods gave differing results, indicating that the extraction procedure is crucial in the determination of the concentration and ratios of nonstructural carbohydrates in onion bulbs. O'Donoghue et al.'s method (O'Donoghue, E. M.; Somerfield, S. D.; Shaw, M.; Bendall, M.; Hedderly, D.; Eason, J.; Sims, I. J. Agric. Food Chem. 2004, 52, 5383-5390), which utilized a more polar solvent (62.5% (v/v) aqueous methanol) and also had the benefit of shorter extraction times and lower temperatures, was far superior to 80% (v/v) ethanol-based methods in extracting significantly greater amounts of fructose, glucose, and sucrose from all onion bulbs tested. Discrepancies between and within cultivars tested also demonstrated that the ratio of monosaccharides to sucrose was affected by extraction method, such that some caution should be given to interpreting some previous work on elucidating the nonstructural carbohydrate composition in onion.}, } @article {pmid17467681, year = {2008}, author = {Verguts, T and Van Opstal, F}, title = {A colorful walk, but is it on the mental number line? Reply to Cohen Kadosh, Tzelgov, and Henik.}, journal = {Cognition}, volume = {106}, number = {1}, pages = {558-63; discussion 564-7}, doi = {10.1016/j.cognition.2007.03.011}, pmid = {17467681}, issn = {0010-0277}, mesh = {*Association Learning ; *Color Perception ; Concept Formation ; Humans ; *Imagination ; *Mathematics ; }, abstract = {Cohen Kadosh, Tzelgov, and Henik [Cohen Kadosh, R., Tzelgov, J., and Henik, A. (2008). A synesthetic walk on the number line: The size effect. Cognition, 106, 548-557] present a new paradigm to probe properties of the mental number line. They describe two experiments which they argue to be inconsistent with the exact small number model proposed by Verguts, Fias, and Stevens [Verguts, T., Fias, W., Stevens, M. (2005). A model of exact small-number representation. Psychonomic Bulletin and Review, 12, 66-80]. We discuss the data, assumptions, and conclusions of Cohen Kadosh et al.'s paper in relation to existing models of numerical cognition.}, } @article {pmid17464888, year = {2007}, author = {Emerson, BC}, title = {Alarm bells for the molecular clock? No support for Ho et al.'s model of time-dependent molecular rate estimates.}, journal = {Systematic biology}, volume = {56}, number = {2}, pages = {337-345}, doi = {10.1080/10635150701258795}, pmid = {17464888}, issn = {1063-5157}, mesh = {Animals ; Classification/methods ; DNA, Mitochondrial/chemistry ; *Evolution, Molecular ; Genetic Speciation ; Geography ; Hominidae/genetics ; Humans ; *Models, Genetic ; *Phylogeny ; Time Factors ; }, } @article {pmid17464884, year = {2007}, author = {Ereshefsky, M}, title = {Foundational issues concerning taxa and taxon names.}, journal = {Systematic biology}, volume = {56}, number = {2}, pages = {295-301}, doi = {10.1080/10635150701317401}, pmid = {17464884}, issn = {1063-5157}, mesh = {Classification/methods ; *Models, Biological ; *Phylogeny ; *Terminology as Topic ; }, abstract = {In a series of articles, Rieppel (2005, Biol. Philos. 20:465-487; 2006a, Cladistics 22:186-197; 2006b, Systematist 26:5-9), Keller et al. (2003, Bot. Rev. 69:93-110), and Nixon and Carpenter (2000, Cladistics 16:298-318) criticize the philosophical foundations of the PhyloCode. They argue that species and higher taxa are not individuals, and they reject the view that taxon names are rigid designators. Furthermore, they charge supporters of the individuality thesis and rigid designator theory with assuming essentialism, committing logical inconsistencies, and offering proposals that render taxonomy untestable. These charges are unsound. Such charges turn on confusions over rigid designator theory and the distinction between kinds and individuals. In addition, Rieppel's, Keller et al.'s, and Nixon and Carpenter's proposed alternatives are no better and have their own problems. The individuality thesis and rigid designator theory should not be quickly abandoned.}, } @article {pmid17431011, year = {2007}, author = {Glymour, MM}, title = {Invited commentary: when bad genes look good - APOE*E4, cognitive decline, and diagnostic thresholds.}, journal = {American journal of epidemiology}, volume = {165}, number = {11}, pages = {1239-46; author reply 1247}, doi = {10.1093/aje/kwm092}, pmid = {17431011}, issn = {0002-9262}, mesh = {Aged ; Apolipoprotein E4/*genetics ; Bias ; Cognition Disorders/diagnosis/*epidemiology/genetics ; Dementia/diagnosis/*epidemiology/genetics/mortality ; Disease Progression ; Female ; Humans ; Nonlinear Dynamics ; *Research Design ; Risk Factors ; Survival Analysis ; Uncertainty ; United States/epidemiology ; }, abstract = {Scientific interest frequently focuses on how factors that influence disease onset subsequently affect disease progression. In this commentary, the author discusses four sources of bias that arise in such work. The focus is on Tyas et al.'s analyses (Am J Epidemiol 2007;165:1231-1238) of how the apolipoprotein E *E4 allele, a well-documented risk factor for Alzheimer's disease, influences progression of cognitive impairments from mild or global cognitive impairment to dementia or death. The author addresses four phenomena that can lead to spurious (noncausal) associations between apolipoprotein E *E4 status and rate of progression of cognitive impairments: beginning observations in the middle of a developing pathologic process, survivor bias, uncertainty in the timing of disease diagnosis, and nonlinear disease progression trajectories. Because these sources of bias are potentially relevant in any study of how risk factors for disease onset influence disease progression, the author advocates assessing their likely magnitude in specific contexts when interpreting results.}, } @article {pmid17429149, year = {2007}, author = {Jenkins, M and Menéndez, CC and Amick, BC and Tullar, J and Hupert, N and Robertson, MM and Katz, JN}, title = {Undergraduate college students' upper extremity symptoms and functional limitations related to computer use: a replication study.}, journal = {Work (Reading, Mass.)}, volume = {28}, number = {3}, pages = {231-238}, pmid = {17429149}, issn = {1051-9815}, support = {5T32PE11001/PE/BHP HRSA HHS/United States ; K24 AR 02123/AR/NIAMS NIH HHS/United States ; P60 AR 47782/AR/NIAMS NIH HHS/United States ; }, mesh = {Cross-Sectional Studies ; Female ; Health Services/statistics & numerical data ; Humans ; Male ; Southwestern United States ; *Students ; *Universities ; Upper Extremity/*physiopathology ; *User-Computer Interface ; }, abstract = {PURPOSE: To replicate Hupert et al.'s [5] evaluation of computer-related upper extremity musculoskeletal symptoms, functional limitations, academic performance impact, medication use and health services utilization among a college student population.

SUBJECTS AND METHODS: A cross-sectional survey of undergraduate students living in a single residential dormitory at a private southwestern university who agreed to participate completed the College Computing & Health Survey in the Spring of 2001.

RESULTS: Of the 127 dormitory residents, 116 students participated and 54% reported experiencing symptoms associated with computer usage. Sixty-two percent of students surveyed experienced functional limitations. More women than men reported symptoms, functional limitations and neck and shoulder pain; those with functional limitations reported higher use of medications than other participants.

CONCLUSION: These findings, which match the general findings of the previous research study conducted with the same instrument but in a different college student population, suggest a high level of computer-use-related musculoskeletal symptoms among college students. Universities may want to consider providing ergonomic training designed for college students to: conduct workstation assessments; identify computer related problems (risk factors); and, propose ergonomic solutions.}, } @article {pmid21352116, year = {2007}, author = {Birchwood, M}, title = {Commentary on Tiffin et al.'s 'From commitment to reality - early intervention in psychosis services in England'. Reasons to be cheerful.}, journal = {Early intervention in psychiatry}, volume = {1}, number = {1}, pages = {109}, doi = {10.1111/j.1751-7893.2007.00016.x}, pmid = {21352116}, issn = {1751-7893}, mesh = {Adolescent ; Adult ; Community Mental Health Services/*methods/statistics & numerical data ; *Early Diagnosis ; England ; Humans ; Program Evaluation/*methods ; Psychotic Disorders/*diagnosis/*therapy ; }, } @article {pmid21049358, year = {2006}, author = {Crawford, JR and Garthwaite, PH}, title = {Methods of testing for a deficit in single-case studies: Evaluation of statistical power by Monte Carlo simulation.}, journal = {Cognitive neuropsychology}, volume = {23}, number = {6}, pages = {877-904}, doi = {10.1080/02643290500538372}, pmid = {21049358}, issn = {0264-3294}, abstract = {Testing for the presence of a deficit by comparing a case to controls is a fundamental feature of many neuropsychological single-case studies. Monte Carlo simulation was employed to study the statistical power of two competing approaches to this task. The power to detect a large deficit was low to moderate for a method proposed by Crawford and Howell (1998; ranging from 44% to 63%) but was extremely low for a method proposed by Mycroft, Mitchell, and Kay (2002; ranging from 1% to 13%). The effects of departures from normality were examined, as was the effect of varying degrees of measurement error in the scores of controls and the single case. Measurement error produced a moderate reduction in power when present in both controls and the case; the effect of differentially greater measurement error for the single case depended on the initial level of power. When Mycroft et al.'s method was used to test for the presence of a classical dissociation, it produced very high Type I error rates (ranging from 20.7% to 49.3%); in contrast, the rates for criteria proposed by Crawford and Garthwaite (2005b) were low (ranging from 1.3% to 6.7%). The broader implications of these results for single-case research are discussed.}, } @article {pmid21038282, year = {2005}, author = {Slotnick, SD}, title = {Spatial working memory specific activity in dorsal prefrontal cortex? Disparate answers from fMRI beta-weight and timecourse analysis.}, journal = {Cognitive neuropsychology}, volume = {22}, number = {7}, pages = {905-920}, doi = {10.1080/02643290442000455}, pmid = {21038282}, issn = {0264-3294}, abstract = {Visual spatial processing and object processing rely on dorsal and ventral cortical pathways, respectively. Whether this functional segregation exists in the prefrontal cortex is currently a source of debate. Using functional MRI (fMRI), there has been some evidence that the superior frontal sulcus (within dorsal prefrontal cortex) is specialised for spatial working memory, while ventral prefrontal cortex is associated with object working memory. Employing beta-weight analysis, Postle, Berger, Taich, and D'Esposito (2000) challenged these results, finding no differential activity associated with spatial working memory versus two-dimensional saccades in the superior frontal sulcus. In the present reanalysis of Postle et al.'s data, both beta-weight analysis and event-related timecourse analysis were utilised. Beta-weight analysis results replicated Postle et al.; however, timecourse analysis revealed greater activity associated with spatial working memory versus two-dimensional saccades in the superior frontal sulcus. Thus, identical fMRI data analysed via distinct methods yielded results with different theoretical conclusions.}, } @article {pmid21774148, year = {2005}, author = {Mainland, I and Halstead, P}, title = {The economics of sheep and goat husbandry in Norse Greenland.}, journal = {Arctic anthropology}, volume = {42}, number = {1}, pages = {103-120}, doi = {10.1353/arc.2011.0060}, pmid = {21774148}, issn = {0066-6939}, mesh = {*Animal Husbandry/economics/education/history ; Animals ; Anthropology, Cultural/education/history ; Arctic Regions/ethnology ; *Dairy Products/history ; *Diet/ethnology/history ; Economics/history ; Food Supply/economics/history ; Goats ; Greenland/ethnology ; History, Medieval ; Humans ; *Meat Products/history ; *Population Groups/ethnology/history ; Sheep ; }, abstract = {Insight into the relative importance of sheep and goat herding and of the economic significance of each species (i.e., milk vs. meat vs. wool) in Medieval Greenland is obtained through the application of Halstead et al.'s (2002) criteria for the identification of adult ovicaprine mandibles to faunal assemblages from three Norse farmsteads: Sandnes, V52a, and Ø71S. The economic strategies identified are broadly comparable between the two species and the Eastern and Western Settlement sites examined, and are suggestive of the subsistence production of meat and milk. Comparison with farmsteads elsewhere in Greenland indicates that socio-economic status and/or farmstead size interacted with geographical location in determining the economic strategies employed by the Norse farmers. A broader use of resources and a more varied diet are evident at larger farmsteads in Greenland and this paper suggests that such sites would have been better able than their smaller counterparts to withstand environmental deterioration during the early Middle Ages. These analyses have also confirmed that goats were relatively more common in Norse sites in Greenland than in Norse sites in Iceland, Orkney, or Shetland.}, } @article {pmid25175619, year = {2004}, author = {Kim, J and Kang, DR and Lee, YK and Shin, SM and Suh, I and Nam, CM}, title = {Statistical algorithm in genetic linkage based on haplotypes.}, journal = {Journal of preventive medicine and public health = Yebang Uihakhoe chi}, volume = {37}, number = {4}, pages = {366-372}, pmid = {25175619}, issn = {1975-8375}, abstract = {OBJECTIVES: This study was conducted to propose a new transmission/disequilibrium test (TDT) to test the linkage between genetic markers and diseasesusceptibility genes based on haplotypes. Simulation studies were performed to compare the proposed method with that of Zhao et al. in terms of type I error probability and powers.

METHODS: We estimated the haplotype frequencies using the expectation-maximization (EM) algorithm with parents' genotypes taken from a trio dataset, and then constructed a two-way contingency table containing estimated frequencies to all possible pairs of parents' haplotypes. We proposed a score test based on differences between column marginals and their corresponding row marginals. The test also involved a covariance structure of marginal differences and their variances. In simulation, we considered a coalescent model with three genetic markers of biallele to investigate the performance of the proposed test under six different configurations.

RESULTS: The haplotype-based TDT statistics, our test and Zhao et al.'s test satisfied a type I error probability, but the TDT test based on single locus showed a conservative trend. As expected, the tests based on haplotypes also had better powers than those based on single locus. Our test and that of Zhao et al. were comparable in powers.

CONCLUSIONS: We proposed a TDT statistic based on haplotypes and showed through simulations that our test was more powerful than the single locus-based test. We will extend our method to multiplex data with affected and/or unaffected sibling (s) or simplex data having only one parent's genotype.}, } @article {pmid21038230, year = {2004}, author = {Crawford, JR and Garthwaite, PH and Howell, DC and Gray, CD}, title = {Inferential methods for comparing a single case with a control sample: modified t-tests versus mycroft et al.'s (2002) modified anova.}, journal = {Cognitive neuropsychology}, volume = {21}, number = {7}, pages = {750-755}, doi = {10.1080/02643290342000276}, pmid = {21038230}, issn = {0264-3294}, abstract = {Mycroft, Mitchell, and Kay (2002) have criticised existing inferential methods (e.g., Crawford & Howell, 1998) for comparing a single case with a control sample and propose that such comparisons be made using a modified ANOVA. It is argued that the assumptions made by Mycroft et al. are questionable and, even if they held, would not invalidate Crawford and Howell's method. Crawford and Howell's null hypothesis is that the patient is an observation from the control population whereas Mycroft et al.'s null hypothesis is that the control population and a notional population of patients have a common mean. Even if one accepts Mycroft et al.'s conceptualisation, their arguments only have force if (1) the variance of a notional population of patients was larger than that of the control population, and (2) patients with impaired performance were balanced exactly by patients whose performance had been enhanced relative to controls. Furthermore, the modified ANOVA would have the undesirable consequence of reducing statistical power unnecessarily and it requires users to provide some estimate of the variance of a hypothetical population.}, } @article {pmid19771707, year = {2003}, author = {Gray, NS and Watt, A and Hassan, S and MacCulloch, MJ}, title = {Behavioral indicators of sadistic sexual murder predict the presence of sadistic sexual fantasy in a normative sample.}, journal = {Journal of interpersonal violence}, volume = {18}, number = {9}, pages = {1018-1034}, doi = {10.1177/0886260503254462}, pmid = {19771707}, issn = {0886-2605}, mesh = {*Fantasy ; Female ; Homicide/*psychology ; Humans ; Male ; Reference Values ; Sadism/*psychology ; Sexual Behavior/*psychology ; Surveys and Questionnaires ; Young Adult ; }, abstract = {Burgess, Hartman, Ressler, Douglas, and McCormack noted a high prevalence of certain behavioral and experiential characteristics in sexual murderers and argued for their etiological importance. The present study aimed to measure the prevalence of these indicators in a nonoffending control population and to evaluate whether they identified sadistic sexual fantasy. The prevalence of behavioral and experiential indicators and degree of sadistic sexual interest were measured in 50 healthy nonoffenders. Compared to Burgess et al.'s sexual murderers, higher prevalence levels for most experiential indicators were found, whereas many of the behavioral indicators were less prevalent. Three of the behavioral indicators were significantly associated with the presence of sadistic sexual fantasies. The presence of behavioral indicators that predict sadistic sexual fantasy confirms the importance of these factors in the etiology of the development of sadistic sexual fantasy in both offenders and nonoffenders and may be useful in risk assessment.}, } @article {pmid21888491, year = {2003}, author = {van-der Hofstadt, C and Rodríguez-Marín, J and Quiles, M and Mira, J and Sitges, E}, title = {Illness representation of arterial hypertension in a sample of health professionals and the general public.}, journal = {Psychology, health & medicine}, volume = {8}, number = {1}, pages = {81-87}, doi = {10.1080/1354850021000059287}, pmid = {21888491}, issn = {1354-8506}, abstract = {This work studies the illness representation of high blood pressure in a sample of primary health care professionals and the general public in order to identify possible differences. The examination of illness representation was carried out using a Spanish adaptation of Turk et al.'s (1986) Implicit Model of Illness Questionnaire. This questionnaire assesses nine components: identity, cause, incapacity, cure, personal responsibility, controllability, changeability and chance. The results showed statistically significant differences between the general public and doctors in all the components except controllability. Results also show that nurses' responses are closer to those of the general public in the social and psychological aspects, but not in the technical knowledge of hypertension.}, } @article {pmid19468139, year = {2002}, author = {Wood, C and Pennebaker, D}, title = {Non-government sector Mental Health Data Dictionary and Standard Data Set.}, journal = {Health information management : journal of the Health Information Management Association of Australia}, volume = {30}, number = {4}, pages = {1-14}, doi = {10.1177/183335830203000404}, pmid = {19468139}, issn = {1833-3575}, mesh = {Advisory Committees ; Australia ; Databases, Factual ; Datasets as Topic/*standards ; Dictionaries as Topic ; Mental Health Services/economics/*organization & administration ; Organizations ; }, abstract = {In order to provide a framework for standardised data reporting in the Australian non-government community mental health sector, a Data Dictionary and standard data set were developed. Advisory Committee and key stakeholder consultation, review of local and national minimum data sets and stakeholder validation informed this process. This resulted in a Data Dictionary containing 37 items and a standard data set containing 15 items. These items conform to the Australian Institute of Health & Welfare's (AIHW) standards and address Leginski et al.'s (1989) decision standards.}, } @article {pmid24441606, year = {1998}, author = {Zur, A and Shinar, D}, title = {Older people's driving habits, visual abilities, and subjective assessment of daily visual functioning.}, journal = {Work (Reading, Mass.)}, volume = {11}, number = {3}, pages = {339-348}, doi = {10.3233/WOR-1998-11312}, pmid = {24441606}, issn = {1051-9815}, abstract = {OBJECTIVES: To explore the relationship between the status of daily visual functions, as measured by Mangione et al.'s (1992) ADVS, and: (a) visual functions that are related to driving; (b) the tendency of elderly people to drive in different visual conditions; and (c) the reasons older people give for limiting their driving under different conditions.

STUDY DESIGN: The subjects were 80 elderly people, ages 64-85. Seventy three of these people still drove and seven had quit driving. Each participant was individually administered (a) a subjective questionnaire containing the ADVS and questions from the Established Populations for the Epidemiological Studies of the Elderly (EPESE); (b) objective measures of visual performance including visual acuity, contrast sensitivity, and visual search speed.

RESULTS: Strong correlations were obtained between the responses to the subjective questionnaire and the objective measures of visual skills. Most subjects were cognizant of the changes in their quality of vision and changed their driving habits accordingly by avoiding driving at dark, on unfamiliar roads, and on long trips. There were also significant associations between the changes in driving behavior and performance on the vision tests.

CONCLUSION: The ADVS can be used as a self-administered test of driving-related visual functioning, and is most relevant to self-restrictions in night driving.}, } @article {pmid21331839, year = {1997}, author = {Peterzell, DH}, title = {Hemisphericsymmetries in the identification of band-pass filtered letters Reply to Christman et al. (1997).}, journal = {Psychonomic bulletin & review}, volume = {4}, number = {2}, pages = {285-287}, pmid = {21331839}, issn = {1069-9384}, abstract = {Christman, Kitterle, and Niebauer (1997) have examined the hypothesis that the two cerebral hemispheres are specialized for processing different ranges of spatial frequency. Their two experiments partially replicated an experiment of Peterzell, Harvey, and Hardyck (1989), who used Sergent's (1982) letter identification paradigm with spatial-frequency band-pass filtered letters as stimuli. We acknowledge the unusual strengths of Christman et al.'s experiments, but argue that the results support the original conclusion of Peterzell et al.: The results are not attributable to hemispheric asymmetries in spatial frequency processing.}, } @article {pmid21153114, year = {1996}, author = {Köves, K and Chen, IL and Görcs, TJ and Scammell, JG and Arimura, A}, title = {Different ultrastructural localization of VIP and prolactin in anterior pituitary cells of rats chronically treated with estrogen.}, journal = {Endocrine}, volume = {5}, number = {2}, pages = {219-223}, pmid = {21153114}, issn = {1355-008X}, abstract = {In the present study we investigated the effect of a long-term estrogen treatment on the intracellular distribution of VIP immunoreactivity in pituitary prolactin cells using double-labeling immunocytochemistry. With the use of pre-embedding ABC method it was found that VIP immunoreactivity was associated with the outer surface of membrane-bound organelles, and was not found in secretory granules. However, prolactin immunoreactivity demonstrated by postembedding immunogold technique was mainly associated within the secretory granules of the same cells. The discrepancy between our and Hsu et al.'s results (1989), who observed VIP immunoreactivity in secretory granules of human anterior pituitary cells, may be owing to the overstimulation of VIP cells by estrogen. It is possible that estrogen treatment depleted the VIP content of the secretory granules and enhanced the cytosolic VIP. The appearance of an alternative form of VIP in estrogen-treated rats with preferential distribution in the cytosol cannot be excluded.}, } @article {pmid21102934, year = {1996}, author = {Lehan, JP}, title = {Determination of grain size in indium tin oxide films from transmission measurements.}, journal = {Applied optics}, volume = {35}, number = {25}, pages = {5048-5051}, doi = {10.1364/AO.35.005048}, pmid = {21102934}, issn = {1559-128X}, abstract = {The grain size of In(2)O(3):Sn thin films on transparent substrates is determined. The method employs the ratio of specular to total transmission to deduce the film grain size. Interpretation of these data is accomplished with the aid of Bhattacharyya et al.'s model [Vacuum 43, 1201 (1992)] of a polycrystalline thin film. This is combined with knowledge of scattering cross-correlation laws. Finally, a simple correction is derived for the scattering contribution from the substrate. Although approximate, the results for the grain size obtained by the reported optical method and by scanning electron microscopy were in agreement within experimental uncertainties.}, } @article {pmid22242611, year = {1996}, author = {Follette, W and Callaghan, G}, title = {The importance of the principle of clinical significance-defining significant to whom and for what purpose: a response to tingey, lambert, burlingame, and hansen.}, journal = {Psychotherapy research : journal of the Society for Psychotherapy Research}, volume = {6}, number = {2}, pages = {133-143}, doi = {10.1080/10503309612331331658}, pmid = {22242611}, issn = {1050-3307}, abstract = {Tingey, Lambert, Burlingame, and Hansen (1996) argue that although there are benefits and utility of clinical significance, extensions to the concept proposed a decade ago (Jacobson, Follette, & Revenstorf, 1984a) are necessary. The criticisms of the original paper and subsequent extensions are problematic and fail to appreciate the underlying principle of clinical significance, namely defining for whom and for what purpose significant change would be identified. This paper responds to several of the criticisms outlined in Tingey et al. with regard to operationalizing a comparison group, the perceived limitations of using two distributions, and the problems with their approach of specifying a method for determining whether groups are distinct. We then propose that there is a principle that underlies the concept of clinical significance that should be appreciated. We conclude by describing under what conditions "functional" distributions may be supplemented by including information to allow comparisons of outcomes with the current best available treatment alternative, but offer a cautionary statement about the potential risks run by extensions such as Tingey et al.'s that can obscure the concept of clinical significance to the point that researchers are no longer discussing change in terms meaningful to the client.}, } @article {pmid18296206, year = {1993}, author = {Ramchandran, K and Vetterli, M}, title = {Best wavelet packet bases in a rate-distortion sense.}, journal = {IEEE transactions on image processing : a publication of the IEEE Signal Processing Society}, volume = {2}, number = {2}, pages = {160-175}, doi = {10.1109/83.217221}, pmid = {18296206}, issn = {1057-7149}, abstract = {A fast rate-distortion (R-D) optimal scheme for coding adaptive trees whose individual nodes spawn descendents forming a disjoint and complete basis cover for the space spanned by their parent nodes is presented. The scheme guarantees operation on the convex hull of the operational R-D curve and uses a fast dynamic programing pruning algorithm to markedly reduce computational complexity. Applications for this coding technique include R. Coefman et al.'s (Yale Univ., 1990) generalized multiresolution wavelet packet decomposition, iterative subband coders, and quadtree structures. Applications to image processing involving wavelet packets as well as discrete cosine transform (DCT) quadtrees are presented.}, } @article {pmid18218441, year = {1993}, author = {Wang, G and Lin, TH and Cheng, P and Shinozaki, DM}, title = {A general cone-beam reconstruction algorithm.}, journal = {IEEE transactions on medical imaging}, volume = {12}, number = {3}, pages = {486-496}, doi = {10.1109/42.241876}, pmid = {18218441}, issn = {0278-0062}, abstract = {Considering the characteristics of the X-ray microscope system being developed at SUNY at Buffalo and the limitations of available cone-beam reconstruction algorithms, a general cone-beam reconstruction algorithm and several special versions of it are proposed and validated by simulation. The cone-beam algorithm allows various scanning loci, handles reconstruction of rod-shaped specimens which are common in practice, and facilitates near real-time reconstruction by providing the same computational efficiency and parallelism as L.A. Feldkamp et al.'s (1984) algorithm. Although the present cone-beam algorithm is not exact, it consistently gives satisfactory reconstructed images. Furthermore, it has several nice properties if the scanning locus meets some conditions. First, reconstruction within a midplane is exact using a planar scanning locus. Second, the vertical integral of a reconstructed image is equal to that of the actual image. Third, reconstruction is exact if an actual image is independent of rotation axis coordinate z. Also, the general algorithm can uniformize and reduce z-axis artifacts, if a helix-like scanning locus is used.}, } @article {pmid24201723, year = {1992}, author = {Dewan, A and Nanda, K and Gupta, SC}, title = {In vitro micropropagation of Acacia nilotica subsp. indica Brenan via cotyledonary nodes.}, journal = {Plant cell reports}, volume = {12}, number = {1}, pages = {18-21}, pmid = {24201723}, issn = {0721-7714}, abstract = {Cotyledonary node explants of Acacia nilotica subspecies indica Brenan, differentiated multiple shoots on Gamborg et al.' s medium (B5, Gamborg et al. 1968) supplemented with cytokinins like N(6)-benzyladenine, 6-(γ, γ-Dimethylallylamino)-purine, kinetin or zeatin. Of the four, BA supported maximum multiple shoot differentiation; the highest average number of shoots (6.3) per expiant was in 1.5 mg/l. The number of shoots was further enhanced by (i) using nodal explants of in vitro regenerated shoots as microcuttings, and (ii) repeated subculture of the original expiants (stumps) on the same medium after excising the shoots. Thus, over seven hundred shoots could be obtained from a single cotyledonary node explant. Individual shoots, when transferred to 2 mg/l indole-3-acetic acid augmented medium organised healthy roots in 100% cultures. Such test tube grown plantlets have been successfully transferred to soil, where they grow well up to eight weeks.}, } @article {pmid22700053, year = {1992}, author = {Sabin, JE}, title = {The therapeutic alliance in managed care mental health practice.}, journal = {The Journal of psychotherapy practice and research}, volume = {1}, number = {1}, pages = {29-36}, pmid = {22700053}, issn = {1055-050X}, abstract = {The author uses Lazare et al.'s "negotiated approach to patienthood" model to address ethical and clinical problems of establishing a therapeutic alliance in the managed care setting. Lazare et al. identified five potential conflicts between therapist and patient that can threaten the therapeutic alliance: conflict over 1) defining the patient's problem; 2) goals of treatment; 3) methods of treatment; 4) conditions of treatment; and 5) the relationship. Case examples illustrate clinically and ethically acceptable ways to work with these conflicts within an expeditious, resource-limited practice style. At times, however, the ethical clinician must act as an advocate for the patient and for change of the system itself.}, } @article {pmid24896510, year = {1984}, author = {Cloarec, A}, title = {[Not Available].}, journal = {Behavioural processes}, volume = {9}, number = {2-3}, pages = {123-133}, doi = {10.1016/0376-6357(84)90034-2}, pmid = {24896510}, issn = {0376-6357}, abstract = {Data from previous experiments on predator-prey distance estimation during ontogeny are compared to theoretical interpretations. In Ranatra the relationships between performance (maximum reactive distances), effectors (length of forelegs) and receptors (eyes) do not remain constant during nymphal development, contrary to Mantids (Maldonado et al., 1973). The hypothesis of an automatic morphological adaptation occurring after each moult cannot be retained. Burkhardt et al.'s (1973) theoretical analysis of binocular vision in insects was applied to Ranatra : for the first four nymphal instars, the calculated limits of binocular vision coincide with maximum reactive distances. This could explain why these animals do not react to prey items presented at distances equal to the length of their forelegs before the 5th instar. The theoretical limits of binocular vision are further away than the maximum capture distances and the length of their forelegs for 5th instar nymphs and adults ; the length of their forelegs would then limit capture possibilities.}, } @article {pmid22058449, year = {1980}, author = {Agarwal, RK and Varma, VK and Dang, R}, title = {Inter-relationship between drug use, anomie, alienation and autthoritarianism amongst university students.}, journal = {Indian journal of psychiatry}, volume = {22}, number = {1}, pages = {103-107}, pmid = {22058449}, issn = {0019-5545}, abstract = {The degree of addictive substance usage score and three personality variables, namely, authoritarianism, alienation, and anomie were measured in 197 university students through a self-administered questionnaire. WHO's Youth Survey Questionnaire for drag use, Varma et al.'s scale of Authoritarianism, Srole's scale of Anomie, and Pearlin's scale of Alienation, were used. A study of the relationship between the co-variables was studied and is discussed.}, } @article {pmid17797084, year = {1976}, author = {Clark, BC and Baird, AK and Rose, HJ and Toulmin, P and Keil, K and Castro, AJ and Kelliher, WC and Rowe, CD and Evans, PH}, title = {Inorganic analyses of martian surface samples at the viking landing sites.}, journal = {Science (New York, N.Y.)}, volume = {194}, number = {4271}, pages = {1283-1288}, doi = {10.1126/science.194.4271.1283}, pmid = {17797084}, issn = {0036-8075}, abstract = {Elemental analyses of fines in the Martian regolith at two widely separated landing sites, Chryse Planitia and Utopia Planitia, produced remarkably similar results. At both sites, the uppermost regolith contains abundant Si and Fe, with significant concentrations of Mg, Al, S, Ca, and Ti. The S concentration is one to two orders of magnitude higher, and K(<0.25 percent by weight) is at least 5 times lower than the average for the earth's crust. The trace elements Sr, Y, and possibly Zr, have been detected at concentrations near or below 100 parts per million. Pebblesized fragments sampled at Chryse contain more S than the bulk fines, and are thought to be pieces of a sulfate-cemented duricrust.}, } @article {pmid20165151, year = {1976}, author = {Boivin, LP}, title = {Diffraction corrections in the radiometry of extended sources.}, journal = {Applied optics}, volume = {15}, number = {5}, pages = {1204-1209}, doi = {10.1364/AO.15.001204}, pmid = {20165151}, issn = {1559-128X}, abstract = {The diffraction corrections associated with a circular aperture in the case of an extended source and a detector located in the fully illuminated region have been calculated in 1972 by Steel, De, and Bell. We have shown recently that the intensity distribution formula that they have used is not accurate in the central region of the diffraction pattern and greatly underestimates the diffraction corrections associated with a point source. In this paper, we take up the case of an extended source; we have followed Steel et al.'s method of calculation, but have used an intensity distribution which we have shown to be valid in the central region. We show that in the case of complex radiation, the variation of the diffraction correction with the source radius rho takes a very simple form: the diffraction correction remains approximately constant as rho increases, until the source and detector subtend equal angles at the center of the aperture; if rho is increased further, the diffraction correction decreses linearly with 1/rho over a certain range of rho. Experimental results are presented that confirm these theoretical predictions.}, } @article {pmid20154950, year = {1975}, author = {Boivin, LP}, title = {Diffraction corrections in radiometry: comparison of two different methods of calculation.}, journal = {Applied optics}, volume = {14}, number = {8}, pages = {2002-2009}, doi = {10.1364/AO.14.002002}, pmid = {20154950}, issn = {1559-128X}, abstract = {We have studied the effect of diffraction on the flux received by a detector located in the fully illuminated region cast by a circular aperture which is placed between a point source and the detector. This case was studied previously by Steel, De, and Bell, who have derived a diffraction correction formula based on an intensity distribution approximation due to Focke. We have derived a diffraction correction formula based on a different type of approximation. The corrections predicted by this formula are much greater than those predicted by Steel et al.'s formula. The validity of our formula and reasons for the discrepancy between the two methods are discussed; some supporting experimental evidence is presented. The case of complex radiation is discussed; it is shown that, under certain conditions, the calculation of diffraction cor rections is very simple.}, } @article {pmid17420042, year = {2007}, author = {Hammarback, B and Mills, S and Johnson, R}, title = {Re: Stone et al.'s "effect of iodine on mercury concentrations in dental-unit wastewater".}, journal = {Dental materials : official publication of the Academy of Dental Materials}, volume = {23}, number = {12}, pages = {1590-2; author reply 1593}, doi = {10.1016/j.dental.2006.12.005}, pmid = {17420042}, issn = {0109-5641}, mesh = {Chloramines/chemistry ; Dental Amalgam ; Dental Disinfectants/*chemistry ; Dental Equipment ; Dental Waste/*analysis ; Iodine/*chemistry ; Medical Waste Disposal/instrumentation ; Mercury/*analysis/chemistry ; Mercury Compounds ; *Waste Disposal, Fluid ; Water Pollution, Chemical ; }, } @article {pmid17400490, year = {2007}, author = {Perez, RS and Collins, S and Marinus, J and Zuurmond, WW and de Lange, JJ}, title = {Diagnostic criteria for CRPS I: differences between patient profiles using three different diagnostic sets.}, journal = {European journal of pain (London, England)}, volume = {11}, number = {8}, pages = {895-902}, doi = {10.1016/j.ejpain.2007.02.006}, pmid = {17400490}, issn = {1090-3801}, mesh = {Adult ; Aged ; Diagnostic Techniques, Neurological/*standards ; Female ; Humans ; Hyperalgesia/diagnosis ; Male ; Middle Aged ; Outpatients ; Reflex Sympathetic Dystrophy/*diagnosis ; Sensitivity and Specificity ; }, abstract = {Complex Regional Pain Syndrome type I (CRPS I) is an illness which usually occurs due to major or minor tissue injury to the extremities. Because a unique pathophysiological mechanism for CRPS I has not yet been established, the diagnosis is based on observation and measurement of clinical symptoms and signs. In this study, a comparison was made between three sets of diagnostic criteria (the IASP, Bruehl et al. and Veldman et al.) based on patient reports and physicians' assessments of signs and symptoms associated with CRPS I, in 372 outpatients suspected of having CRPS I. Agreement between CRPS I diagnosis among the three sets was poor (kappa-range: 0.29-0.42), leading to positive CRPS I diagnoses according to Veldman et al.'s criteria in 218 cases (59%), according to the IASP in 268 cases (72%), and according to Bruehl et al. in 129 cases (35%). Significant differences in patient profiles were found between the diagnostic sets for the number of patients reporting continuing disproportionate pain, larger area affected than the initial trauma (both p<0.001), increase of symptoms due to exercise (p=0.009), edema (p=0.015), temperature asymmetry (p=0.015), hyperesthesia, allodynia (both p<0.001) and hyperalgesia (p=0.036). Similarly, significant differences emerged for physicians' observations of hyperesthesia and allodynia (both p<0.001). Highest combined values of sensitivity (SE) and specificity (SP) for the strongest cases of presence (n=108) or absence (n=62) of CRPS I were found for reported hyperesthesia (SE+SP:165%), allodynia (160%), observed color asymmetry (162%), hyperesthesia (157%), temperature asymmetry (154%) and edema (152%). The lack of agreement between the different diagnostic sets for CRPS I and the different clinical profiles that result from it may lead to different therapeutic and study populations, hampering adequate treatment and scientific development for this illness. We propose explicit reference to diagnostic criteria used in studies, and registration in trials of a broad variety of CRPS I features, as used in this study, to make subgroup phenotyping and post hoc analyses based on different diagnostic criteria possible.}, } @article {pmid17400484, year = {2007}, author = {Kesner, RP and Gilbert, PE}, title = {The role of the agranular insular cortex in anticipation of reward contrast.}, journal = {Neurobiology of learning and memory}, volume = {88}, number = {1}, pages = {82-86}, pmid = {17400484}, issn = {1074-7427}, support = {R01 MH065314/MH/NIMH NIH HHS/United States ; }, mesh = {Animals ; Association Learning/*physiology ; Cerebral Cortex/cytology/*physiology ; Male ; Neurons/classification/physiology ; Psychomotor Performance/*physiology ; Rats ; Rats, Long-Evans ; Reaction Time/physiology ; *Reward ; *Set, Psychology ; }, abstract = {Sixteen male Long-Evans rats were tested on a modified version of Flaherty et al.'s [Flaherty, C. F., Turovsky, J., & Krauss, K. L. (1994). Relative hedonic value modulates anticipatory contrast. Physiology and Behavior, 55, 1047-1054.] anticipatory contrast paradigm to assess memory for the anticipation of reward. Prior to testing each rat received either a control or quinolinic acid induced lesion of the agranular insular cortex. In the home cage, each rat was allowed to drink a water solution containing 2% sucrose for 3 min followed by a water solution containing 32% sucrose for 3 min. Across 10 days of testing, the control rats showed significantly increased anticipatory discriminability as a function of days. In contrast, rats with agranular insular cortex lesions failed to show anticipatory discriminability. The results of a preference task revealed that both groups could perceptually discriminate between a 2% and a 32% sucrose solution. The data suggest that the agranular insular cortex may be involved in the anticipation of reward.}, } @article {pmid17395424, year = {2007}, author = {Chen, L and Tokuda, N and Nagai, A}, title = {Capacity analysis for a two-level decoupled Hamming network for associative memory under a noisy environment.}, journal = {Neural networks : the official journal of the International Neural Network Society}, volume = {20}, number = {5}, pages = {598-609}, doi = {10.1016/j.neunet.2006.05.045}, pmid = {17395424}, issn = {0893-6080}, mesh = {Association Learning ; Computer Simulation ; *Environment ; Humans ; *Memory ; *Neural Networks, Computer ; *Noise ; }, abstract = {Our detailed analysis has established that in addition to the advantages of computationally efficiency and easy hardware implementation, the two-level decoupled Hamming network possesses a substantially higher capacity over the single-level Hamming associative memory since the effect caused by Ikeda et al.'s uniform random noise [Ikeda, N., Watta, P., Artiklar, M., & Hassoun, M. (2001). A two-level Hamming network for high performance associative memory. Neural Networks, 14(9), 1189-1200] is much smaller than that caused by the practically more prevalent concentrated noise. We therefore conclude that the two-level decoupled Hamming network with middle-sized windows should be an elegant associative memory model in all the senses of efficiency, hardware implementation and capacity.}, } @article {pmid17385727, year = {2008}, author = {Leventhal, AM and Pettit, JW and Lewinsohn, PM}, title = {Characterizing major depression phenotypes by presence and type of psychomotor disturbance in adolescents and young adults.}, journal = {Depression and anxiety}, volume = {25}, number = {7}, pages = {575-592}, doi = {10.1002/da.20328}, pmid = {17385727}, issn = {1520-6394}, support = {MH40501/MH/NIMH NIH HHS/United States ; MH50522/MH/NIMH NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Comorbidity ; Depressive Disorder, Major/classification/*diagnosis/genetics/psychology ; Diagnosis, Differential ; Female ; Genetic Predisposition to Disease/genetics/psychology ; Humans ; Longitudinal Studies ; Male ; Oregon ; Personality Assessment ; *Phenotype ; Prospective Studies ; Psychomotor Agitation/*classification/*diagnosis/genetics/psychology ; Psychomotor Disorders/classification/*diagnosis/genetics/psychology ; Recurrence ; }, abstract = {Major depressive disorder (MDD) is phenomenologically heterogeneous, which has prompted investigation of intermediate MDD phenotypes based on specific key symptoms. Presence and type of psychomotor disturbance may be an important psychopathologic feature that differentiates clinically distinct forms of juvenile MDD. This study examined the phenotypic status of three putative MDD phenotypes in a community sample of 941 youths: (1) agitated depression (MDD with psychomotor agitation), (2) retarded depression (MDD with psychomotor retardation), and (3) agitated-retarded depression (MDD with psychomotor agitation and retardation within an episode). Hasler et al.'s [2004: Neuropsychopharmacology 29:1765-1781] criteria of specificity (degree of association with relevant symptoms and conditions related to the disease of interest versus other psychiatric conditions), stability (degree of stability over time), and heritability (degree of familial aggregation with relevant conditions) were used to evaluate the phenotypic significance of these subtypes. Results were suggestive that agitated depression was a relatively specific phenotypic syndrome characterized by irritability, arousal, physical complaints, and vulnerability to anxiety disorders and alcohol dependence; low stability across depressive episodes; and low heritability. Agitated-retarded depression was relatively specific and characterized by increased severity, recurrence, vegetative symptoms, suicidal ideation, social impairment, endogeneity, and vulnerability to anxiety disorders and bulimia; low stability across episodes; and modest heritability. Although retarded depression was associated with some specific distinguishing characteristics, most associations were explained by the increased severity of this phenotype. Retarded depression evidenced little stability or heritability. These findings offer partial support of the phenotypic status of agitated and agitated-retarded depression in youths.}, } @article {pmid17383852, year = {2008}, author = {Brown, AM and Whiteside, SP}, title = {Relations among perceived parental rearing behaviors, attachment style, and worry in anxious children.}, journal = {Journal of anxiety disorders}, volume = {22}, number = {2}, pages = {263-272}, doi = {10.1016/j.janxdis.2007.02.002}, pmid = {17383852}, issn = {0887-6185}, mesh = {Adolescent ; Adult ; Anxiety Disorders/diagnosis/*psychology ; Child ; Child Rearing/*psychology ; Data Collection ; Female ; Humans ; Male ; *Object Attachment ; Parent-Child Relations ; Parenting/*psychology ; *Psychology, Child ; Rejection, Psychology ; Self Concept ; Stress, Psychological/diagnosis/*psychology ; Surveys and Questionnaires ; }, abstract = {The present study extended the findings of Muris et al. [Muris, P., Meesters, C., Merckelbach, H., & Hulsenbeck, P. (2000). Worry in children is related to perceived parental rearing and attachment. Behavior Research and Therapy, 38, 487-497] regarding the relations between perceived parental rearing behaviors, self-reported attachment style, and worry in a community sample to a clinical sample of anxious children. Sixty-four children and adolescents, aged 7-18 years, with a primary anxiety disorder completed (a) the EMBU-C, a questionnaire measuring perceptions of parental rearing behaviors, (b) a single-item measure of attachment style, and (c) an index of worry severity. Findings revealed that child rated parental rearing behaviors, particularly parental rejection, were positively related to child worry. Self-reported attachment style was also related to worry, such that children who classified themselves as ambivalently attached reported higher levels of worry than did children who classified themselves as securely attached. Parenting style and attachment were found to make independent contributions to worry. The results are compared to those from Muris et al.'s community study, and implications for future research are discussed.}, } @article {pmid17380543, year = {2007}, author = {Zhao, H and Bang, H and Wang, H and Pfeifer, PE}, title = {On the equivalence of some medical cost estimators with censored data.}, journal = {Statistics in medicine}, volume = {26}, number = {24}, pages = {4520-4530}, doi = {10.1002/sim.2882}, pmid = {17380543}, issn = {0277-6715}, mesh = {Clinical Trials as Topic/statistics & numerical data ; Costs and Cost Analysis/*statistics & numerical data ; Defibrillators, Implantable/economics ; Humans ; Models, Statistical ; Myocardial Infarction/economics/mortality/therapy ; Outcome Assessment, Health Care ; Survival Analysis ; }, abstract = {In clinical trials comparing different treatments and in health economics and outcomes research, medical costs are frequently analysed to evaluate the economical impacts of new treatment options and economic values of health-care utilization. Since Lin et al.'s first finding in the problem of applying the survival analysis techniques to the cost data, many new methods have been proposed. In this report, we establish analytic relationships among several widely adopted medical cost estimators that are seemingly different. Specifically, we report the equivalence among various estimators that were introduced by Lin et al., Bang and Tsiatis, and Zhao and Tian. Lin's estimators are formerly known to be asymptotically unbiased in some discrete censoring situations and biased otherwise, whereas all other estimators discussed here are consistent for the expected medical cost. Thus, we identify conditions under which these estimators become identical and, consequently, the biased estimators achieve consistency. We illustrate these relationships using an example from a clinical trial examining the effectiveness of implantable cardiac defibrillators in preventing death among people who had prior myocardial infarctions.}, } @article {pmid17372657, year = {2007}, author = {Sanabria, D and Lupiáñez, J and Spence, C}, title = {Auditory motion affects visual motion perception in a speeded discrimination task.}, journal = {Experimental brain research}, volume = {178}, number = {3}, pages = {415-421}, pmid = {17372657}, issn = {0014-4819}, mesh = {Acoustic Stimulation ; Adolescent ; Adult ; Auditory Perception/*physiology ; Brain/physiology ; Discrimination Learning/*physiology ; Female ; Humans ; Male ; Motion Perception/*physiology ; Neuropsychological Tests ; Orientation/physiology ; Photic Stimulation ; Psychomotor Performance/*physiology ; Reaction Time/physiology ; Sound Localization/physiology ; Space Perception/physiology ; Time Factors ; }, abstract = {Transient auditory stimuli have been shown to influence the perception of ambiguous 2D visual motion displays (the bouncing-disks effect; e.g. Sekuler et al. in Nature 385:308, 1997). The question addressed here was whether continuous moving auditory stimuli can also influence visual motion perception under the same experimental conditions. In Experiment 1, we used a modification of Sanabria et al.'s (Exp Brain Res 157:537-541, 2004) paradigm (involving an indirect behavioural measure of the bouncing-disks effect), in which the 2D visual display was presented together with either a brief tone, a continuous moving sound, or in the absence of any form of auditory stimulation. Crucially, the results showed that, together with the effect of the brief tone on bouncing trials, the presence of the continuous moving sound speeded-up participants' responses on streaming trials as compared to the brief tone or no sound conditions. The results of a second experiment revealed that the effect of the continuous moving sound reported in Experiment 1 was not caused simply by the presence of continuous auditory stimulation per se.}, } @article {pmid17368592, year = {2007}, author = {Wackermann, J and Allefeld, C}, title = {On the meaning and interpretation of global descriptors of brain electrical activity. Including a reply to X. Pei et al.}, journal = {International journal of psychophysiology : official journal of the International Organization of Psychophysiology}, volume = {64}, number = {2}, pages = {199-210}, doi = {10.1016/j.ijpsycho.2007.02.003}, pmid = {17368592}, issn = {0167-8760}, mesh = {*Algorithms ; Brain/*physiology ; Electrophysiology/*standards ; Humans ; *Models, Neurological ; }, abstract = {Global descriptors of the brain's electrical activity, Sigma, Phi, and Omega, provide a comprehensive characterisation of brain functional states. Recently, Pei et al. [Pei, X., Zheng, C., Zhang, A., Duan, F., Bin, G., 2005. Discussion on "Towards a quantitative characterisation of functional states of the brain: from the nonlinear methodology to the global linear description" by J. Wackermann. Int. J. Psychophysiol. 56, 201-207] discussed the effects of signal power on the global measure of spatial complexity, Omega, and suggested a modification consisting in epoch-wise and channel-wise normalisation of input data to unit power. In the present paper, the basic principles of the global approach are reviewed, and the issues of Pei et al.'s approach are assessed. The original and the modified measures of spatial complexity are compared in two case studies. Numerical simulation shows that both methods veridically estimate small numbers of signal sources, but systematically underestimate as the number increases; the modified method yields a minor relative improvement. A study on real EEG data shows that the two measures sensibly differ only where artefactual inhomogeneities in channel variances affect the data; a combined procedure, consisting in record-wise equalisation of channel variances before Omega calculations, is suggested as the optimal strategy. Differences between the original objectives of the global methodology and the proposed modifications are pointed out and critically discussed.}, } @article {pmid17364651, year = {2007}, author = {Westberg, P and Lundh, LG and Jönsson, P}, title = {Implicit associations and social anxiety.}, journal = {Cognitive behaviour therapy}, volume = {36}, number = {1}, pages = {43-51}, doi = {10.1080/08037060601020401}, pmid = {17364651}, issn = {1650-6073}, mesh = {Adult ; *Association ; Cognition ; Cognitive Behavioral Therapy ; Female ; Galvanic Skin Response/physiology ; Heart Rate ; Humans ; Phobic Disorders/diagnosis/*psychology/therapy ; Psychological Theory ; Severity of Illness Index ; Surveys and Questionnaires ; Vocabulary ; }, abstract = {The aim of this study was to test whether an Implicit Association Test (IAT) with self- and social anxiety-words is sensitive to differences in trait social anxiety, and to an experimental induction of social anxiety. This was performed in the context of a partial replication of a previous study, in which Mauss et al. (2004) compared high and low trait socially anxious individuals before and after a social anxiety induction (an impromptu speech). Mauss et al.'s findings were replicated; that is, (i) the social anxiety induction produced increases in self-rated anxiety, self-rated physiological responses, and actual physiological arousal; and (ii) higher trait social anxiety was associated with stronger self-rated anxiety and stronger self-rated physiological responses, but not with stronger actual physiological responses. In addition, the results showed higher IAT social anxiety scores, both (i) as a result of the social anxiety induction, and (ii) as a function of self-reported trait social anxiety. It is suggested that the IAT may be a useful method for the experimental study of automatic evaluational thought patterns.}, } @article {pmid17357716, year = {2007}, author = {Evans, S and Azzopardi, P}, title = {Evaluation of a 'bias-free' measure of awareness.}, journal = {Spatial vision}, volume = {20}, number = {1-2}, pages = {61-77}, doi = {10.1163/156856807779369742}, pmid = {17357716}, issn = {0169-1015}, mesh = {Awareness/*physiology ; *Bias ; Humans ; *Models, Theoretical ; Photic Stimulation ; Visual Perception/*physiology ; }, abstract = {The derivation of a reliable, subjective measure of awareness that is not contaminated by observers' response bias is a problem that has long occupied researchers. Kunimoto et al. (2001) proposed a measure of awareness (a') which apparently meets this criterion: a' is derived from confidence ratings and is based on the intuition that confidence should reflect awareness. The aim of this paper is to explore the validity of this measure. Some calculations suggested that, contrary to Kunimoto et al.'s intention, a' can vary as a result of changes in response bias affecting the relative proportions of high- and low-confidence responses. This was not evident in the results of Kunimoto et al.'s original experiments because their method may have artificially 'clamped' observers' response bias close to zero. A predicted consequence of allowing response bias to vary freely is that it can result in a' varying from negative, through zero, to positive values, for a given value of discriminability (d'). We tested whether such variations are likely to occur in practice by employing Kunimoto et al.'s paradigm with various modifications, notably the removal of constraints upon the proportions of low- and high-confidence responses, in a visual discrimination task. As predicted, a' varied with response bias in all participants. Similar results were found when a' was calculated from pre-existing data obtained from a patient with blindsight: a' varied through a range of positive results without approaching zero, which is inconsistent with his well-documented lack of awareness. A second experiment showed how response bias could be manipulated to yield elevated values of a'. On the basis of these findings we conclude that Kunimoto's measure is not as impervious to response bias as was originally assumed.}, } @article {pmid17357715, year = {2007}, author = {Solomon, JA}, title = {Intrinsic uncertainty explains second responses.}, journal = {Spatial vision}, volume = {20}, number = {1-2}, pages = {45-60}, doi = {10.1163/156856807779369715}, pmid = {17357715}, issn = {0169-1015}, mesh = {Contrast Sensitivity/*physiology ; Humans ; *Models, Theoretical ; Photic Stimulation ; Psychophysics/methods ; Visual Perception/*physiology ; }, abstract = {In the simplest form of signal-detection theory (SDT), all stimuli give rise to equal-variance Gaussian probability density functions (PDFs) of sensation, with means proportional to stimulus intensity. As this simple SDT cannot accurately describe psychometric functions for two-alternative forced-choice (2AFC) detection experiments, it is commonly modified in one of two ways: with a non-linear transducer or intrinsic uncertainty. Most results can adequately be explained by either modification, but Swets et al.'s (1961) two-response 4AFC (2R4AFC) detection experiment is an exception. Simple SDT cannot predict the relationship between first- and second-response accuracies and non-linear transduction does not help. A previously unacknowledged facet of intrinsic uncertainty is that the same uncertainty required to fit 2AFC psychometric functions also produces an excellent fit to Swets et al.'s 2R4AFC results, without requiring any additional assumptions. This result is derived within the context of a primer on SDT.}, } @article {pmid17350310, year = {2007}, author = {Kuek, A and Ostör, AJ}, title = {Comment on Pavy et al.'s original article "Methotrexate therapy for rheumatoid arthritis: clinical practice guidelines based on published evidence and expert opinion".}, journal = {Joint bone spine}, volume = {74}, number = {2}, pages = {212-3; author reply 213}, doi = {10.1016/j.jbspin.2006.10.004}, pmid = {17350310}, issn = {1778-7254}, mesh = {Arthritis, Rheumatoid/complications/*drug therapy ; Evidence-Based Medicine/*methods ; Humans ; Immunosuppressive Agents/*therapeutic use ; Infections/etiology ; Methotrexate/*therapeutic use ; Perioperative Care/methods ; *Practice Guidelines as Topic ; }, } @article {pmid17348600, year = {2007}, author = {Adkins, AL}, title = {Improving patient outcomes with prayer.}, journal = {Kentucky nurse}, volume = {55}, number = {1}, pages = {6}, pmid = {17348600}, issn = {0742-8367}, abstract = {Matthew's et al.'s (2000) study supported the use of prayer in rheumatoid arthritis patients. The results of this study can be used to support the group's research utilization project to educate nurses about the impact religion and prayer can have on patient outcomes. A suggestion for future research is to include a more widespread age group, ranging from school age children up to the older adult, as study participants. Two feasability issues for educating nurses about the benefits of prayer on patient outcomes are the time and money.}, } @article {pmid17328386, year = {2006}, author = {Ristic, J and Wright, A and Kingstone, A}, title = {The number line effect reflects top-down control.}, journal = {Psychonomic bulletin & review}, volume = {13}, number = {5}, pages = {862-868}, pmid = {17328386}, issn = {1069-9384}, mesh = {*Attention ; Cues ; Discrimination Learning ; Humans ; Imagination ; *Orientation ; *Pattern Recognition, Visual ; Psychophysics ; Reaction Time ; Reversal Learning ; *Set, Psychology ; }, abstract = {Recent evidence indicates that central directional stimuli, such as eyes and arrows, trigger rapid, reflexive shifts of spatial attention. A study by Fischer, Castel, Dodd, and Pratt (2003) suggested that a similar effect might also apply to central numbers, as if a digit's meaning causes attention to be oriented to its relative position on a left-to-right mental number line. However, unlike central eyes and arrows, the orienting effect for central digits emerges slowly, suggesting that top-down endogenous processes may be mediating this effect. Here, we report a series of three experiments that strongly support this hypothesis. Experiment 1 replicated Fischer et al.'s left-to-right number line effect. Experiment 2 showed that this effect could be completely reversed by merely asking participants to imagine a number line running from right to left. Experiment 3 showed that a left-to-right number line effect could be abolished by presenting targets above and below central fixation, as well as to the left and right of center. Experiment 3 also showed that other mental sets, such as imagining a clock, result in attention's being oriented in accordance with where the central digits are represented on a clock face. Together, these data indicate that the spatial representations and attentional orienting related to the perception of digits are both fragile and flexible and depend critically on the top-down spatial mental sets adopted by individuals.}, } @article {pmid17305222, year = {2006}, author = {Engeser, S and Wendland, M and Rheinberg, F}, title = {Nonconscious activation of behavioral goals, a methodologically refined replication.}, journal = {Psychological reports}, volume = {99}, number = {3}, pages = {963-970}, doi = {10.2466/PR0.99.3.963-970}, pmid = {17305222}, issn = {0033-2941}, mesh = {*Achievement ; Adolescent ; Adult ; Attention ; Awareness ; Female ; *Goals ; Humans ; Male ; Middle Aged ; *Paired-Associate Learning ; *Semantics ; *Unconscious, Psychology ; }, abstract = {In four of the five experiments presented by Bargh and colleagues, achievement-related words to prime the goal of doing well subsequently led to better achievement. However, as the experiments used verbs for achievement words and nouns as neutral words, the results might be due to confounding conditions. To avoid this problem, we conducted an online experiment with a 2 (achievement-priming: achievement words, neutral words) x 2 (word class: verbs, nouns) factorial design. 89 men and 123 women whose mean age was 25.8 yr. (SD = 7.1), who were recruited via a student e-mail list of the university and former participants in other experiments, took part. Barge, et al.'s findings that the achievement content is responsible for the priming effect were confirmed. Moderator effects of task difficulty and achievement motivation are discussed.}, } @article {pmid17292698, year = {2007}, author = {Parker, RI and Hagan-Burke, S}, title = {Useful effect size interpretations for single case research.}, journal = {Behavior therapy}, volume = {38}, number = {1}, pages = {95-105}, doi = {10.1016/j.beth.2006.05.002}, pmid = {17292698}, issn = {0005-7894}, mesh = {Behavior Therapy/methods/statistics & numerical data ; Humans ; *Models, Psychological ; Psychology/*methods/statistics & numerical data ; Research Design/*statistics & numerical data ; }, abstract = {An obstacle to broader acceptability of effect sizes in single case research is their lack of intuitive and useful interpretations. Interpreting Cohen's d as "standard deviation units difference" and R2 as "percent of variance accounted for" do not resound with most visual analysts. In fact, the only comparative analysis widely supported in single case research (SCR) is "percent of nonoverlapping data." This article explores five alternative interpretations of Cohen's d and R2 effect sizes that may be more acceptable to the SCR field. They are: (a) Cohen's (Cohen, J. (1988). Statistical power analysis for the behavioral sciences (2nd ed.). Hillsdale, NJ: Lawrence Erlbaum) "Percent of Nonoverlapping Data" (CPND), (b) Parker et al.'s (Parker, R.I., Cryer, J., Byrns, G., 2006. Controlling trend in single case research. School Psychology Quarterly, 21, 418-440, Parker, R.I., Hagan-Burke, S., Vannest, K., in press. Percent of all non-overlapping data (PAND): An alternative to PND. Journal of Special Education) "Percent of All Nonoverlapping Data" (PAND), (c) Rosenthal et al. (Rosenthal, R., Rosnow, R., & Rubin, D. (2000). Contrasts and effect sizes in behavioral research: A correlational approach. Cambridge: Cambridge University Press.) "Binomial Effect Size Display" (BESD), (d) "Percentile Rank in Control Group" (PR), and (e) McGraw and Wong's (McGraw, K. O., & Wong, S. P. (1992). A common language effect-size statistic. Psychological Bulletin, 111, 361-365) "Common Language Effect Size" (CLES). Each of the five interpretation schemes are applied to a published data set and are evaluated according to (a) intuitive appeal, (b) relevance to visual analysis, (c) ease of calculation, and (d) technical adequacy. Three of the five appear to be improvements over prevailing practice.}, } @article {pmid17279532, year = {2007}, author = {Hróbjartsson, A and Gøtzsche, PC}, title = {Powerful spin in the conclusion of Wampold et al.'s re-analysis of placebo versus no-treatment trials despite similar results as in original review.}, journal = {Journal of clinical psychology}, volume = {63}, number = {4}, pages = {373-377}, doi = {10.1002/jclp.20357}, pmid = {17279532}, issn = {0021-9762}, mesh = {Denmark ; Humans ; Meta-Analysis as Topic ; *Placebo Effect ; *Psychotherapy ; Randomized Controlled Trials as Topic ; *Treatment Outcome ; }, abstract = {B. E. Wampold, T. Minami, S. C. Tierney, T. W. Baskin, and K. S. Bhati (2005) re-analyzed trials included in our systematic review of randomized clinical trials that compared placebo with no treatment (A. Hróbjartsson & P. C. Gøtzsche, 2001). Based on 11 trials, B. E. Wampold et al. concluded that " ... the placebo effect is robust" (p. 850). We (2001) concluded, based on 130 trials, that "we found little evidence in general that placebos have powerful clinical effects" (p. 1599). In this commentary, we examine the reasons for this discrepancy. For trials with continuous outcomes, our analyses (82 trials) and that of B. E. Wampold et al. (5 trials) resulted in pooled standardized mean differences that were small and essentially identical: -0.28 (95% confidence interval = -0.38 to -0.19) versus -0.29 (95% confidence interval = -0.52 to -0.06). There was considerable risk of bias (e.g., reporting bias, sample-size bias). Similarly, for trials with binary outcomes, our analysis (32 trials) and that of B. E. Wampold et al. (6 trials) found no statistically significant pooled effect of placebo interventions and were essentially identical: relative risk 0.95 (95% confidence interval = 0.88-1.02) versus odds ratio 0.99 (95% confidence interval = 0.81-1.23). Thus, B. E. Wampold et al.'s conclusion was not substantiated by their data, and is best characterized as powerful spin. .}, } @article {pmid17279527, year = {2007}, author = {Wampold, BE and Imel, ZE and Minami, T}, title = {The story of placebo effects in medicine: evidence in context.}, journal = {Journal of clinical psychology}, volume = {63}, number = {4}, pages = {379-90; discussion 405-8}, doi = {10.1002/jclp.20354}, pmid = {17279527}, issn = {0021-9762}, mesh = {Clinical Trials as Topic ; *Evidence-Based Medicine ; Humans ; *Placebo Effect ; Psychotherapy ; Treatment Outcome ; United States ; }, abstract = {In 2005, in an article reviewing the evidence related to the placebo effect that was derived from clinical trials in medicine and psychotherapy, B. E. Wampold, T. Minami, S. C. Tierney, T. W. Baskin, and K. S. Bhati re-analyzed studies contained in A. Hróbjartsson and P. C. Gøtzsche's (2001) meta-analysis of trials that contained placebo and no-treatment conditions. Whereas Hróbjartsson and Gøtzsche (2001) concluded that the placebo effect was weak at best, Wampold et al. (2005) concluded that it was "robust." Hróbjartsson and Gøtzsche (this issue) challenged Wampold et al.'s (2005) conclusion, claiming essentially that the results of clinical trials containing placebo and no-treatment conditions are not sufficient to claim that the placebo effect exists to any substantial degree. In this article, it is shown that when properly interpreted by considering theory, method, context, and related research, the results of clinical trials support the existence of a placebo effect. In short, the placebo effect appears in those instances where it is expected.}, } @article {pmid17279522, year = {2007}, author = {Wampold, BE and Imel, ZE and Minami, T}, title = {The placebo effect: "relatively large" and "robust" enough to survive another assault.}, journal = {Journal of clinical psychology}, volume = {63}, number = {4}, pages = {401-3; discussion 405-8}, doi = {10.1002/jclp.20350}, pmid = {17279522}, issn = {0021-9762}, mesh = {*Evidence-Based Medicine ; Humans ; *Placebo Effect ; Psychotherapy ; Treatment Outcome ; United States ; }, abstract = {The evidence related to the placebo effect is discussed, and it is emphasized that the descriptors "relatively large" and "robust" are appropriate in the context in which they were used. Basic science and clinical trials, when interpreted properly, have revealed that the placebo effect is indeed a real phenomenon. J. Hunsley and R. Westmacott (this issue) as well as A. Hróbjartsson and P. C. Gøtzsche (this issue) are concerned that B. E. Wampold, T. Minami, S. C. Tierney, T. W. Baskin, and K. S. Bhati (2005) overstated the clinical effects of placebo when it was never B. E. Wampold et al.'s (2005) intention to make inferences about clinical utility; however, it is shown that the placebo effect exceeds many accepted medical interventions.}, } @article {pmid17277015, year = {2007}, author = {Zeng, Z and Yin, Y and Huang, AL and Jan, KM and Rumschitzki, DS}, title = {Macromolecular transport in heart valves. I. Studies of rat valves with horseradish peroxidase.}, journal = {American journal of physiology. Heart and circulatory physiology}, volume = {292}, number = {6}, pages = {H2664-70}, doi = {10.1152/ajpheart.01419.2006}, pmid = {17277015}, issn = {0363-6135}, support = {5-R01-HL067383/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; Aortic Valve/*metabolism/ultrastructure ; Biological Transport ; Body Water/metabolism ; Capillary Permeability ; Diffusion ; Endothelium, Vascular/*metabolism/ultrastructure ; Horseradish Peroxidase ; Kinetics ; Macromolecular Substances/*metabolism ; Male ; Microscopy, Electron, Transmission ; Rats ; Rats, Sprague-Dawley ; }, abstract = {The present study aims to experimentally elucidate subtle structural features of the rat valve leaflet and the related nature of macromolecular transport across its endothelium and in its subendothelial space, information necessary to construct a rational theoretical model that can explain observation. After intravenous injection of horseradish peroxidase (HRP), we perfusion-fixed the aortic valve of normal Sprague-Dawley rats and found under light microscopy that HRP leaked through the leaflet's endothelium at very few localized brown spots, rather than uniformly. These spots grew nearly as rapidly with HRP circulation time before euthanasia as aortic spots, particularly when the time axis only included the time the valve was closed. These results suggest that macromolecular transport in heart valves depends not only on the direction normal to, but also parallel to, the endothelial surface and that convection, as well as molecular diffusion, plays an important role in macromolecular transport in heart valves. Transmission electron microscopy of traverse leaflet sections after 4-min HRP circulation showed a very thin (approximately 150 nm), sparse layer immediately beneath the endothelium where the HRP concentration was much higher than that in the matrix below it. Nievelstein-Post et al.'s (Nievelstein-Post P, Mottino G, Fogelman A, Frank J. Arterioscler Thromb 14: 1151-1161, 1994) ultrarapid freezing/rotary shadow etching of the normal rabbit valve's subendothelial space supports the existence of this very thin, very sparse "valvular subendothelial intima," in analogy to the vascular subendothelial intima.}, } @article {pmid17269675, year = {2007}, author = {Young, JD and Ramkrishna, D}, title = {On the matching and proportional laws of cybernetic models.}, journal = {Biotechnology progress}, volume = {23}, number = {1}, pages = {83-99}, doi = {10.1021/bp060176q}, pmid = {17269675}, issn = {1520-6033}, mesh = {*Algorithms ; *Bacterial Physiological Phenomena ; Cell Proliferation ; Cybernetics/*methods ; *Models, Biological ; Monte Carlo Method ; }, abstract = {The Matching and Proportional Laws are heuristic control policies that have found widespread use in cybernetic models of biological systems. Within this context, the laws serve as optimization surrogates for predicting the response of metabolic control circuits that modulate enzyme levels and activities. The key result of the current contribution is to demonstrate clearly the optimality properties of these laws and the assumptions that underlie their development. In doing so, we arrive at generalized versions of the Matching and Proportional Laws that are shown to collapse to the forms originally derived by Kompala et al. (Biotechnol. Bioeng. 1986, 28, 1044-1055) when certain simplifications are applied. As a further line of investigation, we show how Kompala et al.'s cybernetic laws compare with alternative control policies in their ability to describe diauxic growth behavior of microbial cultures. We find that Kompala et al.'s model describes the experimental observations more accurately than other limiting-case models that are either too aggressive or too passive in capturing the mixed-substrate growth rates and intermediate lag periods. Monte Carlo analysis of computational growth experiments in which strains obeying different regulatory policies directly compete for available nutrients reveals that the Matching and Proportional Law policy does not maximize the average growth rate of the culture. However, it allocates metabolic resources more frugally than other policies that outperform it and may be more realistic in reflecting the cell's true fitness-to-cost tradeoff as judged by its agreement with experimental growth data.}, } @article {pmid17252203, year = {2007}, author = {Bruggemann, L and Nixon, RD and Cavenett, T}, title = {Predicting acute anxiety and depression following hip fracture.}, journal = {Journal of behavioral medicine}, volume = {30}, number = {2}, pages = {97-105}, pmid = {17252203}, issn = {0160-7715}, mesh = {Acute Disease ; Aged ; Aged, 80 and over ; Anxiety/*diagnosis/psychology ; Culture ; Depression/*diagnosis/psychology ; Female ; Follow-Up Studies ; Hip Fractures/*psychology/surgery ; Humans ; Internal-External Control ; Male ; Mobility Limitation ; Motivation ; Pain/psychology ; Sick Role ; }, abstract = {: The role of injury-related beliefs and hopelessness on depression and anxiety in the acute phase following hip fracture was investigated in 103 hip fracture patients. Participants were assessed at two time points: as inpatients within one week of their surgery, and then 3-weeks later as outpatients. Abramson et al.'s (1989) theory of hopelessness-related depression was investigated as a possible explanatory model to account for depression following hip fracture. Results indicated that hopelessness mediated the relationship between beliefs regarding personal control and depression at the second assessment. Anxiety at follow-up was predicted by control beliefs whereas physical mobility, acute stress and pain made no significant contribution. This study is the first to provide tentative evidence that post-injury beliefs and hopelessness influence levels of depression and anxiety in hip fracture patients in the acute phase of their injury, and indicates that further study in this area is warranted.}, } @article {pmid17230505, year = {2007}, author = {Bay, JO and Linassier, C and Biron, P and Durando, X and Verrelle, P and Kwiatkowski, F and Rosti, G and Demirer, T and , }, title = {Does high-dose carmustine increase overall survival in supratentorial high-grade malignant glioma? An EBMT retrospective study.}, journal = {International journal of cancer}, volume = {120}, number = {8}, pages = {1782-1786}, doi = {10.1002/ijc.22305}, pmid = {17230505}, issn = {0020-7136}, mesh = {Adolescent ; Adult ; Aged ; Antineoplastic Agents, Alkylating/*administration & dosage ; Carmustine/*administration & dosage ; Combined Modality Therapy ; Female ; Glioblastoma/*mortality/therapy ; Hematopoietic Stem Cell Transplantation ; Humans ; Male ; Middle Aged ; Oligodendroglioma/therapy ; Prognosis ; Retrospective Studies ; Supratentorial Neoplasms/*mortality/therapy ; Survival Rate ; Transplantation, Autologous ; }, abstract = {Radiotherapy plus concomitant and adjuvant temozolomide have demonstrated improved survival for glioblastoma. However, prognosis remains poor. High-doses chemotherapy with carmustine is another way to improve response and survival by increasing the dose delivered. Myelotoxicity imposes autologous stem cell rescue. European Group for Blood and Marrow Transplantation experience of this treatment in patients with high-grade glioma was reported here. A retrospective analysis of 217 patients from European Group for Blood and Marrow Transplantation database was realized. Ninety-six patients underwent complete surgical resection while the 121 others had partial resection or only biopsy and were evaluable for an antitumor effect. Patients received 800 mg/m2 of carmustine intravenously at least 1 month after neurosurgery. Forty-eight to 72 hr after chemotherapy, 108 patients received autologous hematopoietic stem cells from bone marrow harvest and 109 patients autologous hematopoietic stem cells from peripheral blood. Radiotherapy was started approximately 40 days after transplantation. Ten deaths were related to the treatment. Of the 121 patients evaluable for tumor response, 64 (53%) presented an objective response. This protocol appear feasible, but with toxicity-related mortality of 4.5%. Median overall survival was 20 months and median time to treatment failure was 7 months. Overall survival and time to treatment were correlated with age, quality of resection and histological subtypes. In glioblastoma multiforme, age and surgery quality appeared to be prognostic factors. Compared with Stupp et al.'s recent study, this study did not favor high-dose carmustine for patients with glioblastoma multiforme with complete surgical resection.}, } @article {pmid17229404, year = {2007}, author = {Suh, S and Yoon, HW and Lee, S and Chung, JY and Cho, ZH and Park, H}, title = {Effects of syntactic complexity in L1 and L2; an fMRI study of Korean-English bilinguals.}, journal = {Brain research}, volume = {1136}, number = {1}, pages = {178-189}, doi = {10.1016/j.brainres.2006.12.043}, pmid = {17229404}, issn = {0006-8993}, mesh = {Adult ; Brain/*blood supply/physiology ; *Brain Mapping ; Female ; Humans ; Image Processing, Computer-Assisted/methods ; *Magnetic Resonance Imaging ; Male ; *Multilingualism ; Oxygen/blood ; Photic Stimulation ; *Semantics ; }, abstract = {The neural mechanisms underlying the syntactic processing of sentence comprehension in Korean (L1) and English (L2) by late bilinguals were investigated using functional MRI. The Korean native speakers were asked to read sentences with different levels of syntactic complexity in L1 and L2 and respond to comprehension questions concerning the sentences. The syntactic complexity was varied using a center-embedded sentence "The director that the maid introduced ignored the farmer" or a conjoined sentence "The maid introduced the director and ignored the farmer". It was found that the major areas involved in sentence processing such as the left inferior frontal gyrus (IFG), bilateral inferior parietal gyrus, and occipital lobe including cuneus, and lingual gyrus were commonly activated during the processing of both L1 and L2. However, the pattern of activation was different for L1 and L2 in the left IFG. The amount of activation was greater for embedded sentences than for conjoined sentences in L1 while no difference was found in L2. These results suggest that the cortical areas involved with syntactic processing in L1 and L2 are shared, but that the underlying neural mechanisms are different. The findings of the present study are discussed in comparison with Hasegawa et al.'s (Hasegawa, M., Carpenter, P.A., Just, M.A., 2002. An fMRI study of bilingual sentence comprehension and workload. NeuroImage 15, 647-660.) and Yokoyama et al.'s (Yokoyama, S., Okamoto, H., Miyamoto, T., Yoshimoto, K., Kim, J., Iwata, K., Jeong, H., Uchida, S., Ikuta, N., Sassa, Y., Nakamura, W., Horie, K., Sato, S., Kawashima, R., 2006. Cortical activation in the processing of passive sentences in L1 and L2: An fMRI study. NeuroImage 30, 570-579.) studies which also found common areas of activation but different patterns of activation during the processing of L1 and L2.}, } @article {pmid17224618, year = {2007}, author = {Poh, N and Martin, A and Bengio, S}, title = {Performance generalization in biometric authentication using joint user-specific and sample bootstraps.}, journal = {IEEE transactions on pattern analysis and machine intelligence}, volume = {29}, number = {3}, pages = {492-498}, doi = {10.1109/TPAMI.2007.55}, pmid = {17224618}, issn = {0162-8828}, mesh = {*Algorithms ; *Artificial Intelligence ; Biometry/*methods ; Computer Simulation ; Face/*anatomy & histology ; Humans ; Image Interpretation, Computer-Assisted/*methods ; Models, Statistical ; Pattern Recognition, Automated/*methods ; Reproducibility of Results ; Sensitivity and Specificity ; *Speech Recognition Software ; }, abstract = {Biometric authentication performance is often depicted by a detection error trade-off (DET) curve. We show that this curve is dependent on the choice of samples available, the demographic composition and the number of users specific to a database. We propose a two-step bootstrap procedure to take into account the three mentioned sources of variability. This is an extension to the Bolle et al.'s bootstrap subset technique. Preliminary experiments on the NIST2005 and XM2VTS benchmark databases are encouraging, e.g., the average result across all 24 systems evaluated on NIST2005 indicates that one can predict, with more than 75 percent of DET coverage, an unseen DET curve with eight times more users. Furthermore, our finding suggests that with more data available, the confidence intervals become smaller and, hence, more useful.}, } @article {pmid17220189, year = {2007}, author = {Zeng, Z and Yin, Y and Jan, KM and Rumschitzki, DS}, title = {Macromolecular transport in heart valves. II. Theoretical models.}, journal = {American journal of physiology. Heart and circulatory physiology}, volume = {292}, number = {6}, pages = {H2671-86}, doi = {10.1152/ajpheart.00608.2006}, pmid = {17220189}, issn = {0363-6135}, support = {5-R01-HL067383/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; Aortic Valve/*metabolism ; Biological Transport ; Blood Flow Velocity ; Blood Pressure ; Body Water/metabolism ; Capillary Permeability ; *Coronary Circulation ; Diffusion ; Endothelium, Vascular/*metabolism ; Horseradish Peroxidase ; Kinetics ; Lipoproteins, LDL/metabolism ; Macromolecular Substances/*metabolism ; Male ; *Models, Cardiovascular ; Pulsatile Flow ; Rats ; Rats, Sprague-Dawley ; Saimiri ; }, abstract = {This paper proposes a new, two-dimensional convection-diffusion model for macromolecular transport in heart valves based on horseradish peroxidase (HRP) experiments on rats presented in the first of the papers in this series (Part I; Zeng Z, Yin Y, Huang AL, Jan KM, Rumschitzki DS. Am J Physiol Heart Circ Physiol 292: H2664-H2670, 2007). Experiments require two valvular intimae, one underneath each endothelium. Tompkins et al. (Tompkins RG, Schnitzer JJ, Yarmush ML. Circ Res 64: 1213-1223, 1989) found large variations in shape and magnitude in transvalvular (125)I-labeled low-density lipoprotein (LDL) profiles from identical experiments on four squirrel monkeys. Their one-dimensional, uniform-medium diffusion-only model fit three parameters independently for each profile; data variability resulted in large parameter spreads. Our theory aims to explain their data with one parameter set. It uses measured parameters and some aortic values but fits the endothelial mass transfer coefficient (k(a)=k(v)=1.63 x 10(-8) cm/s, where subscripts a and v indicate aortic aspect and ventricular aspect, respectively) and middle layer permeability (K(p(2))=2.28 x 10(-16)cm(2)) and LDL diffusion coefficient [D(2)(LDL)=5.93 x 10(-9) cm(2)/s], using one of Tompkins et al.'s profiles, and fixes them throughout. It accurately predicts Part I's rapid localized HRP leakage spot growth rate in rat leaflets that results from the intima's much sparser structure, dictating its far larger transport parameters [K(p(1))= 1.10 x 10(-12)cm(2), D(1)(LDL/HRP)=1.02/4.09 x 10(-7)cm(2)/s] than the middle layer. This contrasts with large arteries with similarly large HRP spots, since the valve has no internal elastic lamina. The model quantitatively explains all of Tompkins et al.'s monkey profiles with these same parameters. Different numbers and locations of isolated macromolecular leaks on both aspects and different section-leak(s) distances yield all profiles.}, } @article {pmid17217185, year = {2006}, author = {Lazzeri, G and Giallombardo, D and Guidoni, C and Zani, A and Casorelli, A and Grasso, A and Pozzi, T and Rossi, S and Giacchi, M}, title = {Nutritional surveillance in Tuscany: eating habits at breakfast, mid-morning and afternoon snacks among 8-9 y-old children.}, journal = {Journal of preventive medicine and hygiene}, volume = {47}, number = {3}, pages = {91-99}, pmid = {17217185}, issn = {1121-2233}, mesh = {*Body Mass Index ; Child ; *Diet Surveys ; *Feeding Behavior ; Female ; Humans ; Italy/epidemiology ; Male ; Mothers/education ; Obesity/*epidemiology ; Overweight ; Prevalence ; Surveys and Questionnaires ; Thinness ; Time Factors ; }, abstract = {INTRODUCTION: The prevalence of overweight and obesity in children is rapidly increasing in many countries. For that it has been interesting to investigate the eating habits of 8-9 y-old Tuscany children by paying attention to their meals frequency per day and their food choices in total and in relation to children's Body Mass Index (BMI) classes. In addition we considered some environment factors that could affect the children eating behaviours, such as mother's BMI and their education level.

METHODS: A statistical sample of 3076 (1583 males, 1493 females), 8-9 year-old school-children was collected; weight and height were measured using standardized personnel and instruments. BMI classes were calculated using Cole et al.'s cutoff for children and adolescents. In order to evaluate the consumption frequency of individual meals and various foods, a Food Frequency Questionnaire (FFQ) was used, which was completed by the children themselves at school. A self-administered questionnaire revealed the weight and height of parents and their educational levels. Three educational levels were established: high, medium and low.

RESULTS: The results showed that 92.3% of children ate breakfast from 4-7 times a week, the vast majority at home, while only 3% declared consuming breakfast never or almost never The most preferred breakfast consisted of milk and biscuits for all children's BMI classes. 95.9% of children reported having midmorning snack at school; fruit juice and tea are the most frequently consumed liquid foods, and pizza, salami sandwiches and pre-packaged snacks are the most frequently consumed solid foods in all BMI classes. 93.6% ate afternoon snack for the most part at home, even if 12% of children reported consuming it elsewhere; fruit juice and tea with pizza, sandwiches and pre-packaged snacks are still the most highly consumed foods by all children's BMI classes. The consumption frequency of breakfast (P < 0.001), mid-morning (P < 0.05) and afternoon snack (P < 0.05) of 8-9 y-old Tuscany children decrease with increase the children's BMI classes. The same tendency may be noted for the consumption frequency of breakfast in relation to mother's BMI (P < 0.05) and their education level (P < 0.05). This data strengthens the thesis that some home environments can affect the children's eating behaviours.

CONCLUSION: No substantial differences in food choices at the meals analyzed were determined among normal weight, overweight and obese children. Children of normal weight had a greater tendency to consume meals more regularly. Mother's BMI and their education level can have influence on children's eating behaviours.}, } @article {pmid17209417, year = {2006}, author = {Rusconi, E and Umiltà, C and Galfano, G}, title = {Breaking ranks: space and number may march to the beat of a different drum.}, journal = {Cortex; a journal devoted to the study of the nervous system and behavior}, volume = {42}, number = {8}, pages = {1124-1127}, doi = {10.1016/s0010-9452(08)70224-7}, pmid = {17209417}, issn = {0010-9452}, mesh = {Attention/physiology ; Humans ; Mental Processes/*physiology ; Psychomotor Performance/physiology ; Reaction Time/physiology ; Space Perception/*physiology ; }, abstract = {Number processing can evoke spatial representations and cause lateralized attention shifts. The article by Wood et al. suggests interesting considerations about the mental space of numbers by pointing to a difference between physical and numerical space processing. We read Wood et al.'s findings in a perspective that takes into consideration a currently debated issue, that is the relation between Simon and SNARC effects. By pointing to a difference between peripheral onsets and numerical targets, indeed, their finding suggests that the hypothesis of a complete overlap between Simon and SNARC effects is less plausible than a partial overlap hypothesis.}, } @article {pmid17186121, year = {2007}, author = {Blanchard, R}, title = {Supplementary analyses regarding Langevin, Langevin, and Curnoe's (2007) findings on fraternal birth order in homosexual men.}, journal = {Archives of sexual behavior}, volume = {36}, number = {4}, pages = {610-4; discussion 615-6}, doi = {10.1007/s10508-006-9134-3}, pmid = {17186121}, issn = {0004-0002}, mesh = {Age Factors ; *Birth Order ; Family Characteristics ; Homosexuality/psychology/*statistics & numerical data ; Humans ; Male ; Paraphilic Disorders/*epidemiology/psychology ; Research Design ; Sex Offenses/psychology/*statistics & numerical data ; }, abstract = {A recent article by Langevin, Langevin, and Curnoe (2007) reported mixed results regarding the fraternal birth order effect, that is, the repeatedly observed finding that older brothers correlate with homosexuality in later-born males. Using a fraternal birth order index computed as older brothers minus younger brothers, Langevin et al. found that the "homoerotic" probands were born later among their brothers than were the "heteroerotic" probands in their full sample (N = 1194) and in their subsample over age 19 (N = 1122), but not in their subsample over age 31 (N = 698) or in their subsample with mothers over age 46 at the proband's birth (N = 727). The present writer concluded that the results obtained with the larger samples are more reliable, based on analyses demonstrating that (1) the larger samples are unlikely to be seriously affected by incomplete sibships, and (2) the smaller samples have poor statistical power. A separate analysis, based on an approximate reconstruction of Langevin et al.'s raw data, indicated that their heteroerotic probands reported a ratio of 104 older brothers per 100 older sisters, which is close to the normative population value of 106, whereas their homoerotic probands reported a ratio of 137, indicating a statistically significant excess of older brothers. These results suggest that Langevin et al.'s data showed significant evidence of a fraternal birth order effect and that their data were consistent with previous studies of this phenomenon.}, } @article {pmid17154788, year = {2006}, author = {Inhoff, AW and Radach, R and Eiter, B}, title = {Temporal overlap in the linguistic processing of successive words in reading: reply to Pollatsek, Reichle, and Rayner (2006a).}, journal = {Journal of experimental psychology. Human perception and performance}, volume = {32}, number = {6}, pages = {1490-1495}, pmid = {17154788}, issn = {0096-1523}, support = {R01 HD043405/HD/NICHD NIH HHS/United States ; }, mesh = {*Attention ; *Fixation, Ocular ; Humans ; *Mental Processes ; Models, Psychological ; Psycholinguistics ; *Reading ; Saccades ; }, abstract = {A. Pollatsek, E. D. Reichle, and K. Rayner argue that the critical findings in A. W. Inhoff, B. M. Eiter, and R. Radach are in general agreement with core assumptions of sequential attention shift models if additional assumptions and facts are considered. The current authors critically discuss the hypothesized time line of processing and indicate that the success of Pollatsek et al.'s simulation is predicated on a gross underestimation of the pretarget word's viewing duration in Inhoff et al. and that the actual data are difficult to reconcile with the strictly serial attention shift assumption. The authors also discuss attention shifting and saccade programming assumptions in the E-Z Reader model and conclude that these are not in harmony with research in related domains of study.}, } @article {pmid17154778, year = {2006}, author = {Laloyaux, C and Destrebecqz, A and Cleeremans, A}, title = {Implicit change identification: a replication of Fernandez-Duque and Thornton (2003).}, journal = {Journal of experimental psychology. Human perception and performance}, volume = {32}, number = {6}, pages = {1366-1379}, doi = {10.1037/0096-1523.32.6.1366}, pmid = {17154778}, issn = {0096-1523}, mesh = {Analysis of Variance ; Attention ; *Awareness ; Belgium ; *Discrimination, Psychological ; Humans ; Models, Psychological ; Pattern Recognition, Visual ; Reaction Time ; Signal Detection, Psychological ; Visual Fields ; *Visual Perception ; }, abstract = {Using a simple change detection task involving vertical and horizontal stimuli, I. M. Thornton and D. Fernandez-Duque (2000) showed that the implicit detection of a change in the orientation of an item influences performance in a subsequent orientation judgment task. However, S. R. Mitroff, D. J. Simons, and S. L. Franconeri (2002) were not able to replicate this finding after correcting for confounds and thus attributed Thornton and Fernandez-Duque's results to methodological artifacts. Because Mitroff et al.'s failure to replicate might in turn have stemmed from several methodological differences between their study and those of Thornton and Fernandez-Duque (2000) and Fernandez-Duque and Thornton, the current authors set out to conduct a further replication in which they corrected all known methodological biases identified so far. The results suggest that implicit change detection indeed occurs: People's conscious decisions about the orientation of an item appear to be influenced by previous undetected changes in the orientation of other items in the display. Implications of this finding in light of current theories of visual awareness are discussed.}, } @article {pmid17154755, year = {2006}, author = {Le, H and Schmidt, FL}, title = {Correcting for indirect range restriction in meta-analysis: testing a new meta-analytic procedure.}, journal = {Psychological methods}, volume = {11}, number = {4}, pages = {416-438}, doi = {10.1037/1082-989X.11.4.416}, pmid = {17154755}, issn = {1082-989X}, mesh = {Humans ; *Meta-Analysis as Topic ; *Models, Psychological ; Psychology/methods/statistics & numerical data ; }, abstract = {Using computer simulation, the authors assessed the accuracy of J. E. Hunter, F. L. Schmidt, and H. Le's (2006) procedure for correcting for indirect range restriction, the most common type of range restriction, in comparison with the conventional practice of applying the Thorndike Case II correction for direct range restriction. Hunter et al.'s procedure produced more accurate estimates of both the mean and standard deviation in meta-analysis than the conventional procedure. Even when its key assumption that the effect of selection on a 3rd variable is fully mediated by the independent variable was violated, Hunter et al.'s procedure was still relatively more accurate than the conventional procedure. When applied to data from a previously published meta-analysis, the new procedure yielded results that led to different substantive conclusions.}, } @article {pmid17148146, year = {2005}, author = {Beekman, M and Oldroyd, BP}, title = {Honeybee workers use cues other than egg viability for policing.}, journal = {Biology letters}, volume = {1}, number = {2}, pages = {129-132}, pmid = {17148146}, issn = {1744-9561}, mesh = {Animals ; *Bees ; Cues ; Female ; Oviparity/physiology ; Ovum/*physiology ; Selection, Genetic ; *Social Behavior ; }, abstract = {Worker policing, wherein social insect workers prevent their sisters from reproducing by eating worker-laid eggs, is recognized as a textbook example of kin selection in action. However, the evolutionary basis of policing was recently challenged in a study that suggested that police-workers remove worker-laid eggs not because rearing workers' sons reduces worker fitness, but merely because worker-laid eggs have low viability. Here, we refute Pirk et al.'s conclusions. First, we confirm earlier work that showed equal viability of eggs laid by queens and workers. Second, a statistical analysis of the data of Pirk et al. reveals that their own data do not support the conclusion that worker-laid eggs are policed merely because of their low viability. Third, we present data that unequivocally show that police-workers cannot discriminate between dead and live eggs. Hence, our study seriously weakens the challenge to the kin-selected basis of policing in honeybees.}, } @article {pmid17147283, year = {2006}, author = {Okumura, M and Shiono, H and Inoue, M and Sawa, Y}, title = {[Clinical and functional aspects of the World Health Organization histologic classification of thymic epithelial tumors].}, journal = {Nihon Geka Gakkai zasshi}, volume = {107}, number = {6}, pages = {257-261}, pmid = {17147283}, issn = {0301-4894}, mesh = {Carcinoma/*classification/genetics/immunology/*pathology ; Chromosome Deletion ; Humans ; Myasthenia Gravis/etiology ; Thymus Neoplasms/*classification/genetics/immunology/*pathology ; *World Health Organization ; }, abstract = {The World Health Organization (WHO) histologic classification was presented by the international committee to provide a universal system for clinicians and researchers in 1999 and was further modified in 2004. This classification is mainly based on Müller-Hermelink et al.'s system and six distinct types were defined. Thymomas were classified into type A, AB, B1, B2, and B3 tumors, according to the shape and atypia of epithelial cells and also the abundance of lymphocytes. Another type of tumor is thymic carcinomas, which have apparent atypia of neoplastic cells. Neuroendocrine tumor (carcinoid) of the thymus was categorized as thymic carcinoma because of the resemblance of genetic aberrations. Several studies have shown that the WHO histologic type is correlated with the proportion of invasive tumors and is an independent prognostic factor along with Masaoka stage. Furthermore, association with myasthenia gravis, ability to induce CD4+CD8+T cells and express HLA-DR molecules, and chromosomal imbalances such as loss of heterogeneity were found to be correlated with the WHO histologic type. Thus, the WHO histologic classification system reflects the oncologic, immunologic, and genetic characteristics of thymic epithelial tumors. The clinical application of this classification system is expected.}, } @article {pmid17139555, year = {2007}, author = {Rind, B and Tromovitch, P}, title = {National samples, sexual abuse in childhood, and adjustment in adulthood: a commentary on Najman, Dunne, Purdie, Boyle, and Coxeter (2005).}, journal = {Archives of sexual behavior}, volume = {36}, number = {1}, pages = {101-6; discussion 107-9}, doi = {10.1007/s10508-006-9058-y}, pmid = {17139555}, issn = {0004-0002}, mesh = {*Adaptation, Psychological ; Adult ; Australia ; Child ; Child Abuse, Sexual/*psychology ; Crime Victims/*psychology ; Female ; Humans ; Interpersonal Relations ; Male ; Middle Aged ; Sexual Dysfunctions, Psychological/*psychology ; Sexual Partners/psychology ; Social Adjustment ; }, abstract = {This article comments on the Najman, Dunne, Purdie, Boyle, and Coxeter (2005) study on the relationship between childhood sexual abuse (CSA) and later sexual functioning in an Australian national sample. We note the value of the Najman et al. study, being well conducted and using a generalizable sample, but critique Najman et al.'s interpretation that their study showed "significant impairment" due to the CSA. We computed effect sizes to show that the "effects" were small, and then show using meta-analysis that these small effects were consistent with results in a series of national samples from other countries. We argue that Najman et al.'s causal statement about CSA's "impairment" effect was unwarranted given their lack of causal analysis, the well-established fact in other research that CSA is often confounded with third variables, and the fact that CSA was confounded with a key third variable in Najman et al.'s study. Given the hyperbole that surrounds the issue of CSA, we emphasize the need for researchers to adhere to valid scientific principles in inference and precision when reporting the results of CSA research.}, } @article {pmid17134326, year = {2007}, author = {Sundararajan, S and Shevade, S and Keerthi, SS}, title = {Fast generalized cross-validation algorithm for sparse model learning.}, journal = {Neural computation}, volume = {19}, number = {1}, pages = {283-301}, doi = {10.1162/neco.2007.19.1.283}, pmid = {17134326}, issn = {0899-7667}, mesh = {*Algorithms ; *Artificial Intelligence ; Least-Squares Analysis ; *Linear Models ; }, abstract = {We propose a fast, incremental algorithm for designing linear regression models. The proposed algorithm generates a sparse model by optimizing multiple smoothing parameters using the generalized cross-validation approach. The performances on synthetic and real-world data sets are compared with other incremental algorithms such as Tipping and Faul's fast relevance vector machine, Chen et al.'s orthogonal least squares, and Orr's regularized forward selection. The results demonstrate that the proposed algorithm is competitive.}, } @article {pmid17131649, year = {2006}, author = {Kehrer, L and Meinecke, C}, title = {A 'first stage' central performance drop in a Gabor luminance-modulation detection task.}, journal = {Spatial vision}, volume = {19}, number = {5}, pages = {427-437}, doi = {10.1163/156856806778457359}, pmid = {17131649}, issn = {0169-1015}, mesh = {Color Perception/*physiology ; Contrast Sensitivity/*physiology ; Humans ; *Lighting ; Photic Stimulation ; Retina/*physiology ; Sensory Thresholds ; Space Perception/*physiology ; Visual Fields ; }, abstract = {In an experiment, 20 participants had to detect a backward masked Gabor luminance-modulation target imposed on a field of uniform luminance at varying eccentricities along the horizontal meridian. Different spatial frequencies were used as target modulations. Results for a 7.0 c/deg target patch showed peak detection performance at the center of the visual field and a steady decrease toward the periphery. For 1.0 c/deg, 0.75 c/deg, and 0.5 c/deg target patches, in contrast, the peak was several degrees off retinal center and decreased steadily toward the center. Findings not only confirmed the familiar sensitivity loss toward peripheral areas for high spatial frequencies, but also indicated a sensitivity loss toward central areas for low spatial frequencies. It is concluded that they further support Gurnsey et al.'s (1996) 'mismatch hypothesis' extending its scope to also include 'first-stage' stimuli.}, } @article {pmid17131646, year = {2006}, author = {Kurki, I and Saarinen, J}, title = {Detection of irregular spatial structures.}, journal = {Spatial vision}, volume = {19}, number = {5}, pages = {375-388}, doi = {10.1163/156856806778457368}, pmid = {17131646}, issn = {0169-1015}, mesh = {Humans ; Orientation/physiology ; Pattern Recognition, Visual/*physiology ; Psychophysics/methods ; Sensory Thresholds ; }, abstract = {Wilson et al.'s (1997) study on Glass patterns suggested that the integration of stimulus features into a linear shape occurs quite locally, whereas curved structures--such as circular--require global summation. Their conclusion was based on experiments in which they varied the size of the signal area containing a spatial structure. In the present study, we tested the integration of constant-sized linear and curved Glass patterns by varying their global irregularity. If the mechanisms underlying the detection of a Glass pattern pool features globally throughout the stimulus, the irregularity should have a strong effect on detection performance. The irregular Glass patterns were composed of a variable number of sub-areas, each of which contained its own linear or curved structure. The structural irregularity impaired the detection of the curved patterns, whereas the thresholds for the linear patterns were not affected. Thus, our results are in line with the notion that the integration of curved Glass patterns occurs more globally than the integration of linear patterns.}, } @article {pmid17100521, year = {2006}, author = {Festa, EK and Ott, BR and Heindel, WC}, title = {Considering phasic alerting in Alzheimer's disease: comment on Tales et al. (2006).}, journal = {Neuropsychology}, volume = {20}, number = {6}, pages = {757-60; discussion 761-2}, doi = {10.1037/0894-4105.20.6.757}, pmid = {17100521}, issn = {0894-4105}, mesh = {Aged ; Alzheimer Disease/*psychology ; Attention/physiology ; Cues ; Discrimination, Psychological/physiology ; Humans ; Orientation/physiology ; Psychomotor Performance/physiology ; Research Design ; Space Perception/physiology ; }, abstract = {A. Tales, R. J. Snowden, M. Brown, and G. Wilcock (2006) have questioned the authors' view of a possible interdependence between attentional systems mediating exogenous spatial orienting and phasic alerting as well as the authors' suggestion that phasic alerting deficits in patients with Alzheimer's disease (AD) may be influencing their performance on tests of spatial orienting. Consistent with this possibility, both laboratories have previously demonstrated increased spatial orienting and decreased phasic alerting in patients with AD. In Tales et al.'s current study, however, they have instead suggested that their results provide evidence for functional independence between these attentional systems in AD. In this commentary, the authors address the misinterpretations of their study and evaluate the degree to which Tales et al.'s study addresses the issues that they raise. Given Tales et al.'s difficulty performing analyses on response time data because of variance issues, the presence of a reduced (although not significant) alerting effect in Tales et al.'s AD group (consistent with the authors' previous findings), and a potential floor effect in their measure of alerting, the authors question the validity of Tales et al.'s conclusions and reaffirm their position that not considering interactions among attentional systems can lead to inaccurate characterizations of the mechanisms by which they operate.}, } @article {pmid17087582, year = {2006}, author = {Clark, SE and Abbe, A and Larson, RP}, title = {Collaboration in associative recognition memory: using recalled information to defend "new" judgments.}, journal = {Journal of experimental psychology. Learning, memory, and cognition}, volume = {32}, number = {6}, pages = {1266-1273}, doi = {10.1037/0278-7393.32.6.1266}, pmid = {17087582}, issn = {0278-7393}, mesh = {*Attention ; Conflict, Psychological ; *Cooperative Behavior ; Decision Making ; Humans ; *Judgment ; *Mental Recall ; *Paired-Associate Learning ; Social Conformity ; }, abstract = {S. E. Clark, A. Hori, A. Putnam, and T. J. Martin (2000) showed that collaboration on a recognition memory task produced facilitation in recognition of targets but had inconsistent and sometimes negative effects regarding distractors. They accounted for these results within the framework of a dual-process, recall-plus-familiarity model but showed only weak evidence to support it. The present results of 3 experiments present stronger evidence for Clark et al.'s dual-process view and also show why such evidence is difficult to obtain.}, } @article {pmid17083184, year = {2006}, author = {Dijkers, M}, title = {Comments on van Brakel et al.'s Participation Scale.}, journal = {Disability and rehabilitation}, volume = {28}, number = {21}, pages = {1360-2; author reply 1363-4}, doi = {10.1080/09638280600756810}, pmid = {17083184}, issn = {0963-8288}, mesh = {Algorithms ; Cross-Cultural Comparison ; Developing Countries ; *Persons with Disabilities/rehabilitation/statistics & numerical data ; *Health Status Indicators ; Humans ; Peer Group ; *Public Health/statistics & numerical data ; *Rehabilitation/statistics & numerical data ; *Surveys and Questionnaires/standards ; }, } @article {pmid17080823, year = {2006}, author = {Liu, Z and Moorhead, RJ and Groner, J}, title = {An advanced evenly-spaced streamline placement algorithm.}, journal = {IEEE transactions on visualization and computer graphics}, volume = {12}, number = {5}, pages = {965-972}, doi = {10.1109/TVCG.2006.116}, pmid = {17080823}, issn = {1077-2626}, abstract = {This paper presents an advanced evenly-spaced streamline placement algorithm for fast, high-quality, and robust layout of flow lines. A fourth-order Runge-Kutta integrator with adaptive step size and error control is employed for rapid accurate streamline advection. Cubic Hermite polynomial interpolation with large sample-spacing is adopted to create fewer evenly-spaced samples along each streamline to reduce the amount of distance checking. We propose two methods to enhance placement quality. Double queues are used to prioritize topological seeding and to favor long streamlines to minimize discontinuities. Adaptive distance control based on the local flow variance is explored to reduce cavities. Furthermore, we propose a universal, effective, fast, and robust loop detection strategy to address closed and spiraling streamlines. Our algorithm is an order-of-magnitude faster than Jobard and Lefer's algorithm with better placement quality and over 5 times faster than Mebarki et al.'s algorithm with comparable placement quality, but with a more robust solution to loop detection.}, } @article {pmid17080782, year = {2006}, author = {Wright, S}, title = {Review of Liebman et al.'s 'An integrated treatment program for anorexia nervosa'.}, journal = {Clinical child psychology and psychiatry}, volume = {11}, number = {3}, pages = {475-482}, doi = {10.1177/1359104506065368}, pmid = {17080782}, issn = {1359-1045}, mesh = {Anorexia Nervosa/*therapy ; Family/*psychology ; *Feeding Behavior ; Humans ; Psychological Theory ; }, abstract = {This article reviews the paper by Liebman, Minuchin, and Baker (1974) describing the use of a family meal as part of an integrated treatment approach for anorexia nervosa. The ideas laid out in the paper are described and discussed in terms of the understanding of anorexia nervosa at the time as well as placed in a current clinical and theoretical context. A comment is made on whether or not, in this author's opinion, the paper stands 'the test of time'.}, } @article {pmid17060069, year = {2006}, author = {Liversidge, HM and Chaillet, N and Mörnstad, H and Nyström, M and Rowlings, K and Taylor, J and Willems, G}, title = {Timing of Demirjian's tooth formation stages.}, journal = {Annals of human biology}, volume = {33}, number = {4}, pages = {454-470}, doi = {10.1080/03014460600802387}, pmid = {17060069}, issn = {0301-4460}, mesh = {Adolescent ; Aging/*physiology ; Asia ; Australia ; Canada ; Child ; Child, Preschool ; Europe ; Female ; Humans ; Male ; Sex Characteristics ; Time Factors ; Tooth/anatomy & histology/*growth & development ; }, abstract = {BACKGROUND: Global differences in Demirjian et al.'s method of assessing dental maturity are thought to be due to population differences.

AIM: The aim of this study was to investigate the timing of individual tooth formation stages in children from eight countries.

RESEARCH DESIGN: This was a meta-analysis of previously published data from retrospective cross-sectional studies of dental maturity.

METHOD: Data of mandibular permanent developing teeth from panoramic radiographs (Demirjian's stages) were combined from Australia, Belgium, Canada, England, Finland, France, South Korea and Sweden (n = 9002, ages 2-16.99 years). Age-of-attainment was calculated using logistic regression for each group by sex and meta-analysis of the total. Overlapping 95% confidence intervals of the means was interpreted as no significant difference.

RESULTS: Mean ages for each group and total were significantly different in 65 out of 509 comparisons (p < 0.05). Some of these were of small sample size but there was no consistent pattern. Apex closure of the first molar was significantly later in children from Quebec and this might explain differences found in the dental maturity score.

CONCLUSIONS: These results suggest no major differences in the timing of tooth formation stages between these children. This fails to explain previous findings of differences using Demirjian's dental maturity method.}, } @article {pmid17058019, year = {2007}, author = {Barrett, KR and McBrien, MA}, title = {Chemical and biological assessment of an urban, estuarine marsh in northeastern New Jersey USA.}, journal = {Environmental monitoring and assessment}, volume = {124}, number = {1-3}, pages = {63-88}, pmid = {17058019}, issn = {0167-6369}, mesh = {Animals ; Arsenic/analysis ; Beryllium/analysis ; *Biodiversity ; Cities ; *Environmental Monitoring ; Environmental Pollutants/*analysis ; Geologic Sediments/*chemistry ; Metals, Heavy/*analysis ; Mice ; New Jersey ; Nickel/analysis ; Organic Chemicals/analysis ; Poaceae/chemistry ; *Wetlands ; Zinc/analysis ; }, abstract = {Oritani Marsh in the Hackensack Meadowlands of urbanized northeastern New Jersey USA was assessed in 2000 for vegetation, soil/sediment chemistry, abundance/diversity of benthic invertebrates, and bird and mammal usage. Vegetatively, both marsh and uplands are dominated by tall, dense Phragmites australis. Small patches (less than 2 hectares total) dominated by Spartina spp. were found at the lowest elevations. Soil/sediment cores were sliced into 5 intervals and analyzed for metals, pesticides and volatile/semivolatile organic compounds. Thirteen locations had at least one chemical above Long et al.'s [Environmental Management, 19, 1995, 81--97] "Effects Range-Median" (ERM). Seven metals and nine organics exceeded ERM in at least one sample, with mercury showing the most exceedances. The surface 15 cm interval was generally more contaminated with metals than the 15 to 30 cm interval; the reverse was true for semivolatile organic compounds. Twenty taxa of benthic macroinvertebrates were collected, with each location producing from 1 to 9 taxa. Abundance ranged from 11 to 3,889 individuals/m(2). Number of taxa was moderately (r (2) between 0.40 and 0.70) negatively correlated with zinc, beryllium, nickel and arsenic concentrations; no other chemical's r (2) was above 0.25. Diversity was moderately negatively correlated with arsenic and beryllium. These correlations were unexpected: zinc, beryllium, nickel and arsenic were not the chemicals found at the highest concentrations relative to benchmarks. Number of taxa, abundance and diversity were moderately (negatively) correlated with elevation; organic carbon was moderately (positively) correlated with abundance. All other correlations were weak (r (2) < 0.35). Live traps captured only one mammal species, the meadow jumping mouse. Bird observations revealed 39 species, dominated by a few common species.}, } @article {pmid17039398, year = {2006}, author = {Lee, SS and August, GJ and Bloomquist, ML and Mathy, R and Realmuto, GM}, title = {Implementing an evidence-based preventive intervention in neighborhood family centers: examination of perceived barriers to program participation.}, journal = {The journal of primary prevention}, volume = {27}, number = {6}, pages = {573-597}, pmid = {17039398}, issn = {0278-095X}, support = {MH 63328/MH/NIMH NIH HHS/United States ; }, mesh = {Adult ; Child ; *Community Health Centers ; Evidence-Based Medicine ; Family ; Female ; Health Promotion ; *Health Services Accessibility ; Humans ; Longitudinal Studies ; Male ; Parents/*psychology ; Patient Participation/*psychology ; *Preventive Health Services ; }, abstract = {: This study examined parents' perceived barriers to participation in a multicomponent prevention program implemented by a community agency serving culturally diverse urban neighborhoods. The Early Risers Participation Interview (ER-PI), modeled after Kadzin et al.'s (1997) Barriers to Treatment Participation Scale, was administered to parents (N = 138) of children who were screened for disruptive behavior and were randomized into a two-year intervention condition. Results showed that the perceived barriers score provided significant information in differentiating low and high participators after controlling for child, parent, and family characteristics. Early identification and resolution of parents' perceived barriers to participation may be key to implementing multifaceted preventive programs successfully in inner-city neighborhoods. EDITOR'S STRATEGIC IMPLICATIONS: The authors present promising practices for client engagement and retention. The experimental, longitudinal design is notable, especially in the evaluation of a community-run prevention program.}, } @article {pmid17033967, year = {2006}, author = {Minichiello, MJ and Durbin, R}, title = {Mapping trait loci by use of inferred ancestral recombination graphs.}, journal = {American journal of human genetics}, volume = {79}, number = {5}, pages = {910-922}, pmid = {17033967}, issn = {0002-9297}, support = {//Wellcome Trust/United Kingdom ; }, mesh = {Algorithms ; Alleles ; Antigens, CD/genetics ; Antigens, Differentiation/genetics ; Biological Evolution ; CTLA-4 Antigen ; Case-Control Studies ; Chromosome Mapping/*methods ; Computer Simulation ; Data Interpretation, Statistical ; Databases, Genetic ; Genetic Predisposition to Disease ; Genetics, Population ; Graves Disease/genetics/immunology ; Humans ; Models, Genetic ; Mutation ; *Quantitative Trait Loci ; *Recombination, Genetic ; }, abstract = {Large-scale association studies are being undertaken with the hope of uncovering the genetic determinants of complex disease. We describe a computationally efficient method for inferring genealogies from population genotype data and show how these genealogies can be used to fine map disease loci and interpret association signals. These genealogies take the form of the ancestral recombination graph (ARG). The ARG defines a genealogical tree for each locus, and, as one moves along the chromosome, the topologies of consecutive trees shift according to the impact of historical recombination events. There are two stages to our analysis. First, we infer plausible ARGs, using a heuristic algorithm, which can handle unphased and missing data and is fast enough to be applied to large-scale studies. Second, we test the genealogical tree at each locus for a clustering of the disease cases beneath a branch, suggesting that a causative mutation occurred on that branch. Since the true ARG is unknown, we average this analysis over an ensemble of inferred ARGs. We have characterized the performance of our method across a wide range of simulated disease models. Compared with simpler tests, our method gives increased accuracy in positioning untyped causative loci and can also be used to estimate the frequencies of untyped causative alleles. We have applied our method to Ueda et al.'s association study of CTLA4 and Graves disease, showing how it can be used to dissect the association signal, giving potentially interesting results of allelic heterogeneity and interaction. Similar approaches analyzing an ensemble of ARGs inferred using our method may be applicable to many other problems of inference from population genotype data.}, } @article {pmid17032405, year = {2006}, author = {Matalka, II and Al-Jarrah, OM and Manasrah, TM}, title = {Quantitative assessment of liver fibrosis: a novel automated image analysis method.}, journal = {Liver international : official journal of the International Association for the Study of the Liver}, volume = {26}, number = {9}, pages = {1054-1064}, doi = {10.1111/j.1478-3231.2006.01341.x}, pmid = {17032405}, issn = {1478-3223}, mesh = {Biopsy ; Disease Progression ; Humans ; *Image Processing, Computer-Assisted ; Liver Cirrhosis/*pathology ; Neural Networks, Computer ; Pattern Recognition, Automated ; Reproducibility of Results ; Severity of Illness Index ; }, abstract = {BACKGROUND: Semiquantitative staging of liver fibrosis is a highly subjective procedure and may lead to an uncertainty in judgment regarding the degree of severity and hence the progression of the disease.

AIM: In this work, we present an automated quantification system (AQS) for evaluating the degree of severity of fibrosis in liver biopsies based on Ishak et al.'s classification. Accordingly, liver fibrosis is classified into six classes depending on its severity and progression. The described system is of special value in accurately assessing the prognosis of chronic liver disease.

METHODS: In our method, we tried to approximate the architecture of the fibrosis in the subject sample using texture features and shape representation of the fibrosis structural expansion with an overall accuracy of about 98%.

RESULTS AND CONCLUSION: The presented AQS is considered to be a novel approach in the domain of automatic liver fibrosis quantification. It is a true quantification and intelligent approach that attempts to utilize the current semiquantitative methods of liver fibrosis assessment to turn them into real quantitative ones with significant reduction in variability and subjectivity. We propose that our method can be adopted by a panel of expert liver pathologists and software to be developed and used on a wide scale.}, } @article {pmid17023140, year = {2006}, author = {Yantz, CL and Gavett, BE and Lynch, JK and McCaffrey, RJ}, title = {Potential for interpretation disparities of Halstead-Reitan neuropsychological battery performances in a litigating sample.}, journal = {Archives of clinical neuropsychology : the official journal of the National Academy of Neuropsychologists}, volume = {21}, number = {8}, pages = {809-817}, doi = {10.1016/j.acn.2006.09.001}, pmid = {17023140}, issn = {0887-6177}, mesh = {Adult ; Aged ; Brain Injuries/*psychology ; *Disability Evaluation ; Female ; Humans ; Jurisprudence ; Male ; Malingering/*psychology ; Memory Disorders/*diagnosis/etiology ; Middle Aged ; *Neuropsychological Tests ; Observer Variation ; Reproducibility of Results ; Severity of Illness Index ; }, abstract = {The performances of 110 litigants on seven variables from the Halstead-Reitan neuropsychological battery (HRNB) were used to compare Heaton, Miller, Taylor, and Grant's (2004) Deficit Scale (DS) and Reitan and Wolfson's (1993) Neuropsychological Deficit Scale (NDS). Additional comparisons were made for people who passed or failed the Test of Memory Malingering (TOMM) to determine effects of effort on scores generated by either scoring system. Wilcoxon signed-rank tests revealed that all seven comparisons were significantly different for the full sample (p< or =0.001). The NDS indicated greater levels of impairment compared to DS across all variables. These findings were also obtained when considering effort, though TOMM failure was related to non-significant differences for two variables. These findings suggest that the two scoring systems are not equivalent, with Heaton et al.'s DS resulting in consistently higher identification rates of normal brain functioning compared to those generated from Reitan and Wolfson's NDS system.}, } @article {pmid17022230, year = {2006}, author = {Mainegra-Hing, E and Rogers, DW}, title = {On the accuracy of techniques for obtaining the calibration coefficient N(K) of 192Ir HDR brachytherapy sources.}, journal = {Medical physics}, volume = {33}, number = {9}, pages = {3340-3347}, doi = {10.1118/1.2239198}, pmid = {17022230}, issn = {0094-2405}, support = {R01 CA66852/CA/NCI NIH HHS/United States ; }, mesh = {Brachytherapy/*instrumentation/*methods ; Calibration ; Equipment Design ; Equipment Failure Analysis ; Iridium Radioisotopes/*analysis/*standards ; Radiometry/*methods/*standards ; Radiotherapy Dosage ; Reference Values ; Reproducibility of Results ; Sensitivity and Specificity ; }, abstract = {The accuracy of interpolation or averaging procedures for obtaining the calibration coefficient N(K) for 192Ir high-dose-rate brachytherapy sources has been investigated using the EGSnrc Monte Carlo simulation system. It is shown that the widely used two-point averaging procedure of Goetsch et al. [Med. Phys. 18, 462 (1991)] has some conceptual problems. Most importantly, they recommended, as did the IAEA, averaging A(wall)N(K) values whereas one should average 1/N(K) values. In practice this and other issues are shown to have little effect except for Goetsch et al.'s methods for determining A(wall) values. Their method of generalizing the A(wall) values measured in one geometry to other geometries is incorrect by up to 2%. However, these errors in A(wall) values cause systematic errors of only 0.3% in 192Ir calibration coefficients. It is shown that A(wall) values need not be included in the averaging technique at all, thereby simplifying the technique considerably. It is demonstrated that as long as ion chambers with a flat response are used and/or very heavily filtered 250 kV (or higher) beams of x rays are used in the averaging, then almost all techniques can provide adequate accuracy.}, } @article {pmid16972822, year = {2006}, author = {Butcher, JN and Hamilton, CK and Rouse, SV and Cumella, EJ}, title = {The deconstruction of the Hy Scale of MMPI-2: failure of RC3 in measuring somatic symptom expression.}, journal = {Journal of personality assessment}, volume = {87}, number = {2}, pages = {186-192}, doi = {10.1207/s15327752jpa8702_08}, pmid = {16972822}, issn = {0022-3891}, mesh = {Female ; Humans ; MMPI/*standards ; Male ; Psychology, Clinical/*instrumentation ; Reproducibility of Results ; Somatoform Disorders/*diagnosis ; United States ; }, abstract = {The MMPI-2 (Butcher, Dahlstrom, Graham, Tellegen, & Kaemmer, 1989) Clinical Scales have a long history in psychological assessment. Recently, Tellegen et al. (2003) conducted a series of analyses to restructure the scales to reduce what they considered to be problems that limit scale functioning. In a critique of the Restructured Clinical (RC) Scales published in this issue, Nichols (2006/this issue) questions a number of aspects of the approach Tellegen et al. took including their theoretical assumptions, methods of analysis, and failures to report important information needed for scale evaluation such as relationships with existing scales. We concur with many points raised by Nichols. In our analysis of the performance of the RC3 scale, we found that it has "drifted" so far from the original Hy scale as to be a completely different measure- a scale of cynical attitudes that is already well represented in existing MMPI-2 measures. In this article, we take these concerns a step further and examine the history and construct validity of the Hy scale in evaluating the somatic expression of problems that the original authors (McKinley & Hathaway, 1944) intended. We also include new information from a medical setting, an application not represented in Tellegen et al.'s RC Scale monograph. In agreement with Rogers et al. (2006/this issue), it is our conclusion that some RC Scales do not represent the measurement domain of the original scales and should not be relied on for or used to refine traditional interpretation, particularly in medical or forensic situations (such as personal injury cases) because of their confusing and conflicting results.}, } @article {pmid16972818, year = {2006}, author = {Tellegen, A and Ben-Porath, YS and Sellbom, M and Arbisi, PA and McNulty, JL and Graham, JR}, title = {Further evidence on the validity of the MMPI-2 Restructured Clinical (RC) Scales: addressing questions raised by Rogers, Sewell, Harrison, and Jordan and Nichols.}, journal = {Journal of personality assessment}, volume = {87}, number = {2}, pages = {148-171}, doi = {10.1207/s15327752jpa8702_04}, pmid = {16972818}, issn = {0022-3891}, mesh = {*Evidence-Based Medicine ; Female ; Humans ; MMPI/*standards ; Male ; Psychology, Clinical/*instrumentation ; *Reproducibility of Results ; }, abstract = {The reviews by Rogers, Sewell, Harrison, and Jordan (2006/this issue), and by Nichols (2006/this issue) offer markedly contrasting appraisals of the MMPI-2 Restructured Clinical (RC) Scales introduced by Tellegen et al. (2003). The one common feature is that both reviews draw on the same atypical MMPI-2 (Butcher, Dahlstrom, Graham, Tellegen, & Kaemmer, 1989) data set for their empirical analyses, with results warranting critical scrutiny. Rogers et al.'s critique provides an evaluation of the RC Scales from the perspective of Jackson's (1970) method of test development. One significant issue in Rogers et al.'s review concerns social desirability, prompting us to clarify our own views on this topic. We also highlight and discuss problems associated with Rogers et al.'s use of the unrepresentative data set. Nichols's polemical critique neglects empirical and theoretical support for demoralization as a central construct and misconstrues as "construct drift" the purposeful process of developing the RC scales. Nichols's criticisms and proposals overlook requirements for assessing syndromes and for construct validation and even rudiments of scale development. Our reply incorporates evidence, including new findings, refuting his criticisms and confirming that demoralization is a pervasive MMPI dimension, that the RC Scales capture the major distinctive features of the original Clinical Scales, and that they generate correspondingly meaningful validity patterns.}, } @article {pmid16972817, year = {2006}, author = {Rogers, R and Sewell, KW and Harrison, KS and Jordan, MJ}, title = {The MMPI-2 Restructured Clinical Scales: a paradigmatic shift in scale development.}, journal = {Journal of personality assessment}, volume = {87}, number = {2}, pages = {139-147}, doi = {10.1207/s15327752jpa8702_03}, pmid = {16972817}, issn = {0022-3891}, mesh = {Adult ; Databases, Factual ; Female ; Humans ; *MMPI ; Male ; Middle Aged ; Psychology, Clinical/*instrumentation ; Texas ; }, abstract = {Tellegen et al. (2003) proposed fundamental changes in MMPI-2 (Butcher, Dahlstrom, Graham, Tellegen, & Kaemmer, 1989) scale development by discarding empirical scale development in favor of construct validation via Jackson's (1970) sequential system of scale development. As a result of their efforts, a general distress factor (Demoralization) was identified and 8 Restructured Clinical (RC) Scales were developed. Using 7,330 clinical cases from Caldwell's (1997) data set, in this study, we sought to cross-validate the MMPI-2 RC Scales. Scale homogeneity was confirmed with high alpha coefficients and interitem correlations in the expected range. We also achieved a major objective of reducing interscale correlations. In replicating Tellegen et al.'s principal components analysis, we achieved a high concordance for 6 of the 8 RC Scales. We critically examine these results in light of Jackson's construct validation. We discuss the clinical usefulness of the MMPI-2 RC Scales within the context of current and future research.}, } @article {pmid16961985, year = {2006}, author = {do Canto-Pereira, LH and Paramei, GV and Morya, E and Ranvaud, RD}, title = {Inhibition or facilitation of return: Does chromatic component count?.}, journal = {Visual neuroscience}, volume = {23}, number = {3-4}, pages = {489-493}, doi = {10.1017/S0952523806233261}, pmid = {16961985}, issn = {0952-5238}, mesh = {Adult ; Analysis of Variance ; Attention/*physiology ; *Color ; Color Perception/*physiology ; Cues ; Female ; Humans ; *Inhibition, Psychological ; Male ; Photic Stimulation/methods ; Reaction Time/physiology ; Time Factors ; Visual Pathways/physiology ; }, abstract = {Inhibitory effects have been reported when a target is preceded by a cue of the same color and location. Color-based inhibition was found using red and blue nonisoluminant stimuli (Law et al., 1995). Here we investigate whether this phenomenon depends on the chromatic subsystem involved by employing isoluminant colors varying along either the violet-yellow or purple-turquoise cardinal axis. Experiment 1 replicated Law et al.'s study: After fixating magenta, either a red or blue cue was presented, followed by a magenta "neutral attractor," and, finally, by a red or blue target. In Experiment 2, violet and yellow, cue or target, varied along a tritan confusion line in the CIE 1976 chromaticity diagram. In Experiment 3, purple and turquoise, cue or target, varied along a deutan confusion line in the CIE 1976 chromaticity diagram. Normal trichromats (n = 19) participated in all three experiments. In Experiment 1, color repetition indeed resulted in longer reaction times (RTs) (4.7 ms, P = 0.038). In Experiment 2, however, no significant color repetition effect was found; RTs to violet and yellow were not significantly different, though tending toward slower responses (2 ms) for violet repetition but faster (5 ms) for yellow. Experiment 3 also showed no color repetition effect (P = 0.58); notably, RTs were overall faster for purple than for turquoise (22 ms, P 0.05), but faster for turquoise (7 ms, P > 0.05). These findings demonstrate that color repetition is not always inhibitory but may turn facilitatory depending on the colors employed. The results indicate that disengagement of attention is an unlikely mechanism to be the sole explanation of previously reported color-based inhibition of return. We suggest a complementary, perceptual explanation: response (dis)advantage depends on whether the stimuli are isoluminant and on the opponent chromatic subsystem involved. The choice of the colors employed and the cue-attractor-target constellation also may be of significance.}, } @article {pmid16957883, year = {2007}, author = {Arzamarski, R and Harrison, SJ and Hajnal, A and Michaels, CF}, title = {Lateral ball interception: hand movements during linear ball trajectories.}, journal = {Experimental brain research}, volume = {177}, number = {3}, pages = {312-323}, pmid = {16957883}, issn = {0014-4819}, mesh = {Adolescent ; Adult ; Attention/*physiology ; Discrimination Learning/physiology ; Female ; Functional Laterality/*physiology ; *Hand ; Humans ; Male ; Models, Theoretical ; Motion Perception/*physiology ; Movement/*physiology ; Practice, Psychological ; Psychomotor Performance/*physiology ; }, abstract = {Part of understanding how acts are coordinated is identifying the information that guides movements. In the case of catching a ball within arm's reach, that identification has been complicated by empirical disparities concerning hand-movement reversals during catching. Jacobs and Michaels found unilateral reversals in a paradigm in which balls swung down in an arc; this implicated a particular optical variable, the ratio of lateral velocity to expansion velocity. Montagne et al. reported bilateral reversals when balls approached along a linear trajectory, which implicated a different variable, lateral ball position. The research reported here attempted to replicate Montagne et al.'s findings. In Experiment 1, participants caught balls rolling toward them across a table, under full lighting using monocular or binocular viewing; in Experiment 2, participants caught luminous balls with a luminous glove in an otherwise dark room. Using Montagne et al.'s criterion, we observed no movement reversals in any condition, though some aspects of hand movements suggested the relevance of lateral ball position. The results of Experiment 3, which asked perceivers to indicate only where rods pointed, suggested that lateral position effects were a bias that is unrelated to interception. The ratio of lateral velocity to expansion appears to be a better variable for explaining hand trajectories in lateral interception.}, } @article {pmid16957507, year = {2006}, author = {Fischer, B and Reimer, J and Firestone, M and Kalousek, K and Rehm, J and Heathcote, J}, title = {Treatment for hepatitis C virus and cannabis use in illicit drug user patients: implications and questions.}, journal = {European journal of gastroenterology & hepatology}, volume = {18}, number = {10}, pages = {1039-1042}, doi = {10.1097/01.meg.0000236869.93527.b9}, pmid = {16957507}, issn = {0954-691X}, mesh = {Antiviral Agents/*administration & dosage ; Hepatitis C, Chronic/*drug therapy/psychology/transmission ; Humans ; *Marijuana Smoking/therapy ; Patient Compliance ; Substance-Related Disorders/*complications ; }, abstract = {Illicit drug users are the primary risk group for HCV transmission, and will form the largest HCV treatment population for years to come. Sylvestre et al.'s study suggests that cannabis use may benefit treatment retention and outcomes in illicit drug users undergoing HCV treatment. In fact, there is substantial evidence that cannabis use may help address key challenges faced by drug users in HCV treatment (e.g., nausea, depression), especially when such treatment occurs in the context of methadone maintenance treatment which may amplify these consequences. While further research is required on the biological and clinical aspects of the benefits of cannabis use for HCV treatment, and the effectiveness of cannabis use for HCV treatment needs to be explored in larger study populations, we advocate that in the interim existing barriers to cannabis use are removed for drug users undergoing HCV treatment until the conclusive empirical basis for evidence-based guidance is available.}, } @article {pmid16934484, year = {2006}, author = {Dudekula, S and Fragata, M}, title = {Investigation of the electron transfer site of p-benzoquinone in isolated photosystem II particles and thylakoid membranes using alpha- and beta-cyclodextrins.}, journal = {Journal of photochemistry and photobiology. B, Biology}, volume = {85}, number = {3}, pages = {177-183}, doi = {10.1016/j.jphotobiol.2006.07.003}, pmid = {16934484}, issn = {1011-1344}, mesh = {Benzoquinones/*chemistry ; Electron Transport/*physiology ; Hordeum/*metabolism ; Kinetics ; Oxygen/*metabolism ; Photosystem II Protein Complex/chemistry/*metabolism ; Thylakoids/*metabolism ; alpha-Cyclodextrins/chemistry ; beta-Cyclodextrins/chemistry ; }, abstract = {The electron transfer sites of p-benzoquinone (pBQ) and 2,6-dichloro-p-benzoquinone (DCBQ) were investigated in thylakoid membranes and isolated photosystem II (PSII) particles from barley (Hordeum vulgare) using alpha- and beta-cyclodextrins (CD) at concentrations up to 16 mM. In CD-treated thylakoid membranes incubated with DCBQ the electron transport through PSII, estimated as oxygen evolution (OE), is largely enhanced according to a S-shaped (sigmoidal) dose-response curve displaying a sharp inflection point, or transition. The maxima percent OE enhancement at cyclodextrin concentrations above 14 mM are about 100% (alpha-CD) and 190% (beta-CD). On the contrary, in thylakoid membrane preparations incubated with pBQ as electron acceptor one observes an OE inhibition of about 30% which might result from the depletion of the thylakoid membrane of its plastoquinone content. It was also found that in isolated PSII particles incubated with either pBQ or DCBQ the cyclodextrins induce only a small OE enhancement. Moreover, the observation in CD-treated thylakoid membranes incubated with pBQ of a residual, non-inhibited oxygen-evolving activity of about 70% puts a twofold question. That is, either the plastoquinone depletion was not complete, or, pBQ binds to electron acceptor sites of different nature. From this and data published in the literature, it is concluded that in the thylakoid membrane (i) DCBQ binds to Q(B), as is generally accepted, and (ii) pBQ binds to the plastoquinol molecules in the PQ pool and most likely also to Q(B), thereby in accord with Satoh et al.'s model [K. Satoh, M. Ohhashi, Y. Kashino, H. Koike, Plant Cell Physiol. 36 (1995) 597-605]. An attractive alternative hypothesis is the direct interaction of pBQ with the non-haem Fe(2+) between Q(A) and Q(B).}, } @article {pmid16930166, year = {2006}, author = {Babor, TF and Caetano, R}, title = {Subtypes of substance dependence and abuse: implications for diagnostic classification and empirical research.}, journal = {Addiction (Abingdon, England)}, volume = {101 Suppl 1}, number = {}, pages = {104-110}, doi = {10.1111/j.1360-0443.2006.01595.x}, pmid = {16930166}, issn = {0965-2140}, mesh = {Alcoholism/classification/diagnosis/drug therapy ; Cluster Analysis ; Empiricism ; Humans ; Psychological Theory ; Research Design ; Substance-Related Disorders/*classification/diagnosis/drug therapy ; }, abstract = {AIMS: To evaluate the relevance of a form of diagnostic classification called clinical subtyping in relation to possible revisions in the diagnostic criteria for substance abuse and dependence in psychiatric classification systems.

METHODS: A general rationale for subtyping is presented. To explore the implications for diagnostic classification, recent research on a variety of subtyping schemes is reviewed in terms of the development of new subtypes and the validation of established theories.

RESULTS: Subtypes of alcoholism and other psychiatric disorders have been proposed since the beginning of modern psychiatry. Recent subtyping research suggests that no consensus has emerged about the nature, much less the number, of subtypes that could be used to characterize the clinical heterogeneity assumed to be present in groups of people with substance use disorders. Although several relatively simple binary typologies have been developed (e.g. Cloninger's type I and type II; Babor et al.'s type A and type B), validation research has produced mixed results in terms of the construct, concurrent and predictive validity of these classifications.

CONCLUSIONS: The adoption of a subtyping scheme in the major psychiatric classification systems is not recommended until further international research is conducted.}, } @article {pmid16917887, year = {2006}, author = {Campbell, B}, title = {Adrenarche and the evolution of human life history.}, journal = {American journal of human biology : the official journal of the Human Biology Council}, volume = {18}, number = {5}, pages = {569-589}, doi = {10.1002/ajhb.20528}, pmid = {16917887}, issn = {1042-0533}, mesh = {Adrenarche/*physiology ; Animals ; *Biological Evolution ; Brain/growth & development/metabolism ; Dehydroepiandrosterone Sulfate/*metabolism ; Hominidae/physiology ; Humans ; Longevity/physiology ; Memory/physiology ; Sex Characteristics ; }, abstract = {Adrenarche, the prepubertal onset of adrenal production of dehydroepiandrosterone sulfate (DHEAS), is a distinctive aspect of the human life course. Yet its evolutionary origins remain unexplained. Production of DHEAS is associated with the development of the zona reticularis, a novel histological layer within the adrenal gland, derived from the fetal adrenal gland, and associated with primates more generally. Evidence that DHEAS is a neurosteroid, together with the fact that increases in DHEAS parallel patterns of cortical maturation from approximately age 6 years to the mid-20s, suggests that DHEAS may play an important role in extended brain maturation among humans. DHEAS has demonstrated effects on mood in humans, and acts at neuron receptor sites. I suggest three ways in which DHEAS may play a role in human brain maturation: 1) increasing activity of the amgydala; 2) increasing activity of the hippocampus; and 3) promoting synaptogenesis within the cortex. I propose that associated changes in fearfulness and anxiety, and memory, could act to increase social interaction with nonfamiliar individuals and shape cognitive development. Comparison with the African apes suggests that the timing of adrenarche in chimpanzees may be similar to that in humans, though the full course of age-related changes in DHEAS and their relationship to reproductive and brain maturation are not clear. The role of DHEAS as a physiological mechanism supporting increased brain development, extended life span, and decreased sexual dimorphism is most compatible with Kaplan et al.'s (2000) theory of the evolution of human life history and intergenerational transfers.}, } @article {pmid16900878, year = {2006}, author = {Wilkening, S and Chen, B and Hemminki, K and Försti, A}, title = {STR markers for kinship analysis.}, journal = {Human biology}, volume = {78}, number = {1}, pages = {1-8}, doi = {10.1353/hub.2006.0030}, pmid = {16900878}, issn = {0018-7143}, mesh = {Female ; Finland ; Genetics, Population/*methods ; Genotype ; Humans ; Male ; Poland ; Polymerase Chain Reaction ; Tandem Repeat Sequences/*genetics ; }, abstract = {The analysis of short tandem repeats is a widely used method to estimate relatedness between closely related populations or individuals. The AmpFlSTR PCR Amplification Kit has 15 highly variable autosomal markers of tetranucleotide repeats and is principally made to identify individuals and first- or second-degree relatives. However, in many studies one is searching for individuals who are related through more than one generation. We wanted to test whether the amplification kit can also be used to identify more distantly related individuals. Therefore we compared 16 different methods that calculate genetic distance with regard to each method's ability to cluster more distantly related individuals from two test families. Among all the tested methods Nei et al.'s (1983) DA distance performed well in clustering family members within a group of unrelated individuals for a broad range of scenarios. However, second-degree relatives were difficult to cluster with any of the examined methods when other family members were absent. With a simulation we further estimated how many markers would actually be needed to detect a certain degree of relatedness. According to this simulation, one would need at least 123 independent microsatellite markers to detect third-degree relatives with 90% probability. In conclusion, the 15 STR markers in the amplification kit are suitable for detecting only very closely related individuals or entire families.}, } @article {pmid16899171, year = {2006}, author = {Lloyd, EA}, title = {Response to Puts and Dawood's 'the evolution of female orgasm: adaptation or byproduct?'--Been there.}, journal = {Twin research and human genetics : the official journal of the International Society for Twin Studies}, volume = {9}, number = {4}, pages = {603-608}, doi = {10.1375/183242706778025044}, pmid = {16899171}, issn = {1832-4274}, mesh = {*Adaptation, Physiological ; *Biological Evolution ; Female ; Humans ; *Orgasm/physiology ; }, abstract = {David Puts and Khytam Dawood's recent critique of my book, The Case of the Female Orgasm: Bias in the Science of Evolution, attempts to make plausible an adaptive account of female orgasm based on a hypothesized mechanism of uterine upsuck and sperm competition. Yet the authors fail to respond to the criticisms of such accounts that I detailed previously in my book. They raise a further concern about my definition of adaptation--a red herring--and manufacture a conceptual error regarding heritability that they then attribute to me. Most seriously, they fail to address the glaring failure of sperm competition accounts to accord with evidence from sexology. Specifically, the distribution curve of orgasm-with-intercourse--according to Dawood et al.'s own data, as well as others'--is relatively flat across the various classes. This curve needs to be tested against a well-formed multistrategy adaptive hypothesis; it cannot be explained by the adaptive account defended by Puts and Dawood in their critique.}, } @article {pmid16893219, year = {2006}, author = {Jurak, M and Chibowski, E}, title = {Topography and surface free energy of DPPC layers deposited on a glass, mica, or PMMA support.}, journal = {Langmuir : the ACS journal of surfaces and colloids}, volume = {22}, number = {17}, pages = {7226-7234}, doi = {10.1021/la060585w}, pmid = {16893219}, issn = {0743-7463}, abstract = {An investigation of energetic properties of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) layers deposited on glass, mica, and PMMA (poly(methyl methacrylate)) surfaces was carried out by means of contact angles measurements (advancing and receding) for three probe liquids (diiodomethane, water, and formamide). DPPC was deposited on the surfaces from water (on glass and mica) or methanol (on PMMA) solutions. The topography of the tested surfaces was determined with a help of scanning electron microscopy (SEM) and atomic force microscopy (AFM). Using the measured contact angles, the total apparent surface free energy and its components of the studied layers were determined from van Oss et al.'s (Lifshitz-van der Waals and acid-base components, LWAB) and contact angle hysteresis (CAH) approaches. It allowed us to learn about changes in the surface free energy of the layers (hydrophobicity/hydrophilicity) depending on their number and kind of support. It was found that the changes in the energy greatly depended on the surface properties of the substrate as well as the statistical number of monolayers of DPPC. However, principal changes took place for first three monolayers.}, } @article {pmid16876476, year = {2006}, author = {Shibasaki, H and Hallett, M}, title = {What is the Bereitschaftspotential?.}, journal = {Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology}, volume = {117}, number = {11}, pages = {2341-2356}, doi = {10.1016/j.clinph.2006.04.025}, pmid = {16876476}, issn = {1388-2457}, mesh = {Beta Rhythm ; Cerebral Cortex/*physiology ; Cortical Synchronization ; *Electroencephalography ; Functional Laterality/physiology ; Humans ; Motor Cortex/physiology ; Movement/*physiology ; Movement Disorders/physiopathology ; }, abstract = {Since discovery of the slow negative electroencephalographic (EEG) activity preceding self-initiated movement by Kornhuber and Deecke [Kornhuber HH, Deecke L. Hirnpotentialänderungen bei Willkurbewegungen und passiven Bewegungen des Menschen: Bereitschaftspotential und reafferente Potentiale. Pflugers Archiv 1965;284:1-17], various source localization techniques in normal subjects and epicortical recording in epilepsy patients have disclosed the generator mechanisms of each identifiable component of movement-related cortical potentials (MRCPs) to some extent. The initial slow segment of BP, called 'early BP' in this article, begins about 2 s before the movement onset in the pre-supplementary motor area (pre-SMA) with no site-specificity and in the SMA proper according to the somatotopic organization, and shortly thereafter in the lateral premotor cortex bilaterally with relatively clear somatotopy. About 400 ms before the movement onset, the steeper negative slope, called 'late BP' in this article (also referred to as NS'), occurs in the contralateral primary motor cortex (M1) and lateral premotor cortex with precise somatotopy. These two phases of BP are differentially influenced by various factors, especially by complexity of the movement which enhances only the late BP. Event-related desynchronization (ERD) of beta frequency EEG band before self-initiated movements shows a different temporospatial pattern from that of the BP, suggesting different neuronal mechanisms for the two. BP has been applied for investigating pathophysiology of various movement disorders. Volitional motor inhibition or muscle relaxation is preceded by BP quite similar to that preceding voluntary muscle contraction. Since BP of typical waveforms and temporospatial pattern does not occur before organic involuntary movements, BP is used for detecting the participation of the 'voluntary motor system' in the generation of apparently involuntary movements in patients with psychogenic movement disorders. In view of Libet et al.'s report [Libet B, Gleason CA, Wright EW, Pearl DK. Time of conscious intention to act in relation to onset of cerebral activity (readiness-potential). The unconscious initiation of a freely voluntary act. Brain 1983;106:623-642] that the awareness of intention to move occurred much later than the onset of BP, the early BP might reflect, physiologically, slowly increasing cortical excitability and, behaviorally, subconscious readiness for the forthcoming movement. Whether the late BP reflects conscious preparation for intended movement or not remains to be clarified.}, } @article {pmid16872576, year = {2006}, author = {Mendonça, SC and Gonçalves-Pires, Mdo R and Rodrigues, RM and Ferreira, A and Costa-Cruz, JM}, title = {Is there an association between positive Strongyloides stercoralis serology and diabetes mellitus?.}, journal = {Acta tropica}, volume = {99}, number = {1}, pages = {102-105}, doi = {10.1016/j.actatropica.2006.06.006}, pmid = {16872576}, issn = {0001-706X}, mesh = {Adult ; Aged ; Animals ; Antibodies, Helminth/blood ; Blotting, Western ; Diabetes Mellitus/blood/*parasitology ; Enzyme-Linked Immunosorbent Assay ; Eosinophils/cytology ; Feces/parasitology ; Female ; Fluorescent Antibody Technique, Indirect ; Glycated Hemoglobin/metabolism ; Humans ; Leukocyte Count ; Male ; Middle Aged ; Strongyloides stercoralis/*growth & development ; Strongyloidiasis/blood/*complications/parasitology ; }, abstract = {The purpose of this study was to determine the frequency of association between positive Strongyloides stercoralis serology and diabetes mellitus. A total of 78 diabetic patients and 42 controls were evaluated. For a parasitological diagnosis, Baermann and Hoffman et al.'s methods were applied. The immunological diagnosis involved the indirect fluorescence antibody test, ELISA and Western blotting to detect IgG antibodies. The frequency of positive S. stercoralis serology in diabetics was 23% versus 7.1% in the control group (P<0.05). The odds ratio for diabetics was 3.9 (CI, 1.6-15.9, P<0.05). Diabetic patients with HbA(1c)< or =7 had a greater chance of testing negatively for S. stercoralis infection (OR: 1.5, P>0.05). Provided there are related cases of disseminated strongyloidiasis in diabetics and there is a higher frequency of asymptomaticity of the infection in this group, the immunological screening of these patients at risk could prevent severe and fatal outcomes of the disease.}, } @article {pmid16862337, year = {2006}, author = {Biondo-Simões, Mde L and Matias, JE and Montibeller, GR and Siqueira, LC and Nunes, Eda S and Grassi, CA}, title = {Effect of aging on liver regeneration in rats.}, journal = {Acta cirurgica brasileira}, volume = {21}, number = {4}, pages = {197-202}, doi = {10.1590/s0102-86502006000400002}, pmid = {16862337}, issn = {0102-8650}, mesh = {Aging/*physiology ; Animals ; Cell Count ; Disease Models, Animal ; Hepatectomy ; Liver/physiology/surgery/ultrastructure ; Liver Regeneration/*physiology ; Male ; Mitosis ; Proliferating Cell Nuclear Antigen/analysis ; Rats ; Rats, Wistar ; Wound Healing/physiology ; }, abstract = {PURPOSE: Regeneration and/or healing of tissues is believed to be more difficult in elderly people. The liver is one of the most complex organs in the human body, and is involved in a variety of functions. Liver regeneration is the body's protection mechanism against loss of functional liver tissue. The aim of this study is to identify the regenerative capacity of the liver in older animals and to compare it with that of young adult animals.

METHODS: Thirty-four Wistar rats were used, of which 17 were 90 days old (young animals) and 17 were 460 days old (old animals). Approximately 70% of the liver was surgically removed. Examinations were carried out after 24 hours and on day 7, using 3 methods: KWON et al.'s formula to identify increase in volume; mitotic figure count in 5 fields; and the percentage of PCNA-positive nuclei in 5 fields.

RESULTS: The increase in volume of the remaining liver was greater in the young animals after both 24 hours (p=0.0006) and on day 7 (p=0.0000). Histological cuts showed a greater mitotic figure count in young animals evaluated after 24 hours (p=0.0000). Upon evaluation on day 7, recovery was observed in the old animals. This recovery was similar to that of the young ones (p=0.2851). The PCNA-positive nucleus count was greater in the young animals' liver cuts after 24 hours (p=0.0310), and, while it had decreased in young animals by day 7, recovery was observed in the older animals (p=0.0298).

CONCLUSION: The data confirm that age is related to delay in liver regeneration in rats.}, } @article {pmid16859930, year = {2006}, author = {Cselényi, Z and Olsson, H and Halldin, C and Gulyás, B and Farde, L}, title = {A comparison of recent parametric neuroreceptor mapping approaches based on measurements with the high affinity PET radioligands [11C]FLB 457 and [11C]WAY 100635.}, journal = {NeuroImage}, volume = {32}, number = {4}, pages = {1690-1708}, doi = {10.1016/j.neuroimage.2006.02.053}, pmid = {16859930}, issn = {1053-8119}, mesh = {Algorithms ; Brain/*diagnostic imaging ; Brain Mapping ; Data Interpretation, Statistical ; *Dopamine Antagonists ; Humans ; Image Processing, Computer-Assisted ; *Piperazines ; Positron-Emission Tomography ; *Pyridines ; *Pyrrolidines ; *Radiopharmaceuticals ; Receptor, Serotonin, 5-HT1A/metabolism ; Receptors, Dopamine D2/metabolism ; Reproducibility of Results ; *Salicylamides ; Sample Size ; Sensory Receptor Cells/*physiology ; *Serotonin Antagonists ; Software ; }, abstract = {In positron emission tomography (PET) studies, the detailed mapping of neuroreceptor binding is a trade-off between parametric accuracy and spatial precision. Logan's graphical approach is a straightforward way to quickly obtain binding potential values at the voxel level but it has been shown to have a noise-dependent negative bias. More recently suggested approaches claim to improve parametric accuracy with retained spatial resolution. In the present study, we used PET measurements on regional D2 dopamine and 5-HT1A serotonin receptor binding in man to compare binding potential (BP) estimates of six different parametric imaging approaches to the traditional Logan ROI-based approach which was used as a "gold standard". The parametric imaging approaches included Logan's reference tissue graphical analysis (PILogan), its version recently modified by Varga and Szabo (PIVarga), two versions of the wavelet-based approach, Gunn's basis function method (BFM) and Gunn et al.'s recent compartmental theory-based approach employing basis pursuit strategy for kinetic modeling (called DEPICT). Applicability for practical purposes in basic and clinical research was also considered. The results indicate that the PILogan and PIVarga approaches fail to recover the correct values, the wavelet-based approaches overcome the noise susceptibility of the Logan fit with generally good recovery of BP values, and BFM and DEPICT seem to produce values with a bias dependent on receptor density. Further investigations on this bias and other phenomena revealed fundamental issues regarding the use of BFM and DEPICT on noisy voxel-wise data. In conclusion, the wavelet-based approaches seem to provide the most valid and reliable estimates across regions with a wide range of receptor densities. Furthermore, the results support the use of receptor parametric imaging in applied studies in basic or clinical research.}, } @article {pmid16858638, year = {2006}, author = {Uji, M and Tanaka, N and Shono, M and Kitamura, T}, title = {Factorial structure of the parental bonding instrument (PBI) in Japan: a study of cultural, developmental, and gender influences.}, journal = {Child psychiatry and human development}, volume = {37}, number = {2}, pages = {115-132}, pmid = {16858638}, issn = {0009-398X}, mesh = {Adolescent ; Attitude/*ethnology ; *Culture ; Factor Analysis, Statistical ; Female ; Humans ; Japan ; Male ; *Object Attachment ; *Parent-Child Relations ; *Personality Development ; Rural Population/statistics & numerical data ; Sex Factors ; *Surveys and Questionnaires ; }, abstract = {This study explored the factorial structure of the Parental Bonding Instrument (PBI) in the Japanese population. Several differences between the structure model in the current study and Parker et al.'s original model were identified. We also examined the adaptability of the inventory to children currently being raised by parents. We also developed a structural equation model that takes into account the impacts of the respondents' generation and gender and the caregivers' gender. The cultural, developmental, generational, and gender influences on the factorial structure of the PBI as well as the implications for clinical settings were discussed.}, } @article {pmid16854567, year = {2006}, author = {Moore, DJ and Savla, GN and Woods, SP and Jeste, DV and Palmer, BW}, title = {Verbal fluency impairments among middle-aged and older outpatients with schizophrenia are characterized by deficient switching.}, journal = {Schizophrenia research}, volume = {87}, number = {1-3}, pages = {254-260}, doi = {10.1016/j.schres.2006.06.005}, pmid = {16854567}, issn = {0920-9964}, support = {MH66248-02/MH/NIMH NIH HHS/United States ; P30 MH066248/MH/NIMH NIH HHS/United States ; R01 MH64722/MH/NIMH NIH HHS/United States ; MH19934-10/MH/NIMH NIH HHS/United States ; R01 MH059101/MH/NIMH NIH HHS/United States ; R01 MH064722/MH/NIMH NIH HHS/United States ; MH59101-05/MH/NIMH NIH HHS/United States ; }, mesh = {Age Factors ; Aged ; Aging ; *Ambulatory Care ; Cognition Disorders/*diagnosis/*epidemiology ; Demography ; Humans ; Middle Aged ; Neuropsychological Tests ; Schizophrenia/epidemiology/*physiopathology/*therapy ; Severity of Illness Index ; Speech Disorders/*diagnosis/*epidemiology ; *Verbal Behavior ; }, abstract = {Patients with schizophrenia demonstrate impaired verbal fluency, but no studies have examined the underlying cognitive mechanisms (e.g., clustering and switching) associated with impaired fluency among middle-aged and older, non-institutionalized patients. Using Troyer et al.'s [Troyer, A.K., Moscovitch, M., Winocur, G., 1997. Clustering and switching as two components of verbal fluency: evidence from younger and older healthy adults. Neuropsychology 11 (1), 138-146] conceptual model, we examined clustering and switching on verbal fluency tasks among 163 middle-aged and older outpatients with schizophrenia and 92 age comparable healthy comparison (HC) participants. The patients produced significantly fewer total words than HC participants on both the letter ("F", "A", "S") and Animal fluency conditions. With regard to clustering, patients were similar to HC participants on both FAS and Animal fluency tasks. However, significantly fewer switches between lexical-semantic categories were observed among patients with schizophrenia on both conditions relative to HC participants. A small, but statistically significant association was found between number of switches on the Animal fluency task and severity of negative symptoms. The absence of a difference in mean cluster size between the patient and HC groups suggests intact lexical-semantic stores among middle-aged and older outpatients with schizophrenia. Differences in switching between patients and HC participants may be driven by several cognitive impairments associated with schizophrenia. Further delineation of the cognitive mechanisms of the observed lexical-semantic switching deficits in schizophrenia should be a focus of future research.}, } @article {pmid16843040, year = {2006}, author = {Mulvenna, CM and Walsh, V}, title = {Synaesthesia: supernormal integration?.}, journal = {Trends in cognitive sciences}, volume = {10}, number = {8}, pages = {350-352}, doi = {10.1016/j.tics.2006.06.004}, pmid = {16843040}, issn = {1364-6613}, mesh = {Hallucinations/*pathology/*physiopathology ; Humans ; Models, Neurological ; Parietal Lobe/*physiopathology ; }, abstract = {Synaesthesia has been known to scientific research for over 100 years but has undergone something of a renaissance recently as new investigations begin to uncover its neurological basis. Rather than being an anomaly, it might offer beneficial insights into the basis of normal perception. A new study by Esterman et al. epitomises this current trend and claims to show that the posterior parietal cortex is a crucial locus of synaesthetic experience. As the posterior parietal cortex is commonly linked to normal sensory integration, Esterman et al.'s finding might lend support to the claim that synaesthesia is an extension of the normal perceptual processes assumed to occur in binding.}, } @article {pmid16842953, year = {2006}, author = {Ait El Kadi, M and Aghrouch, M and Seffar, M and El harti, J and Bouklouze, A and Cherrah, Y and Souly, K and Zouhdi, M}, title = {[Prevalence of Acinetobacter baumannii and Pseudomonas aeruginosa isolates resistant to imipenem by production of metallo-beta-lactamase].}, journal = {Medecine et maladies infectieuses}, volume = {36}, number = {7}, pages = {386-389}, doi = {10.1016/j.medmal.2006.05.003}, pmid = {16842953}, issn = {0399-077X}, mesh = {Acinetobacter/drug effects/enzymology/*isolation & purification ; Anti-Bacterial Agents/pharmacology ; Drug Resistance, Bacterial ; Imipenem/*pharmacology ; Pseudomonas aeruginosa/drug effects/enzymology/*isolation & purification ; beta-Lactamases/*metabolism ; }, abstract = {UNLABELLED: Metallo-beta-lactamases (MBL) are enzymes produced by Gram-negative bacilli such as Pseudomonas aeruginosa and Acinetobacter baumannii. These enzymes make these isolates resistant to imipenem.

AIM: The aim of this study was to determine the prevalence of this resistance mechanism in Pseudomonas aeruginosa and Acinetobacter baumannii strains identified in the bacteriology laboratory of the Rabat Ibn Sina teaching hospital, Morocco.

MATERIALS AND METHOD: Screening for MBL was systematic in all resistant strains and/or strains with decreased sensitivity to imipenem, according to Dongeun Yong et al.'s method, using a sterilized solution of EDTA 0.5 M pH 8.

RESULTS: Eighty-five bacterial strains (48 P. aeruginosa and 37 A. baumannii) were identified 23% (11) and 57% (21) of which were respectively resistant to the imipenem. The prevalence of MbetaL producing strains was 27% for P. aeruginosa and 38% for A. baumannii.

CONCLUSION: These results show that the frequency of these strains is increases in our hospital and that their emergence represents a serious therapeutic and epidemiological problem. This means that we need to implement the supervision of hospital microbial environment and strictly apply hygiene measures.}, } @article {pmid16838933, year = {2005}, author = {Xiao-Yu, K and Kang-Wei, Z}, title = {Quantum-admixture model of high-spin <--> low-spin transition for ferrous complex molecules.}, journal = {The journal of physical chemistry. A}, volume = {109}, number = {44}, pages = {10129-10137}, doi = {10.1021/jp054087s}, pmid = {16838933}, issn = {1089-5639}, mesh = {Ferrous Compounds/*chemistry ; Magnetics ; *Models, Chemical ; *Quantum Theory ; }, abstract = {A quantum-admixture model for the d(6) configuration ferrous complex molecules with the high-spin <--> low-spin transition has been established by using the unified crystal-field-coupling (UCFC) scheme. A general study has been made on the spin transition of octahedrally coordinated d(6) complexes, and a special application has been given to an Fe(II) compound Fe(II)(TRIM)(2)(PhCO(2))(ClO(4)). The results show the following: (i) The quantum picture of the spin transition of a d(6) system, such as Fe(II), is much more complex than a simple transition between the pure (5)T(2g) and (1)A(1g) states as usually understood. In practice, owing to spin-orbit coupling, spin is no longer a good quantum number and there is no longer a pure (5)T(2g) or (1)A(1g) state. Each of them splits into substates and each substate is a linear combination of various multiplets. The high-spin --> low-spin transition of an octahedrally coordinated d(6) ion is practically the crossover of the two lowest substates of (5)T(2g) at the critical point. (ii) At the spin-transition critical point the magnetic moment mu(eff) approximately 5.22 mu(B), which is obviously different from the simple average of the mu(eff) values of high-spin and low-spin states but near the saturation value. (iii) The calculation of the effective molecular magnetic moment mu(eff) for an octahedrally coordinated Fe(II) ion shows that the mu(eff)-T curve is in good agreement with Lemercier et al.'s experiment and both the low-spin value mu(eff) = 0.51 mu(B) and the high-spin value mu(eff) = 5.4 mu(B) are comparable with the experimental values 0.76 mu(B) and 5.4 mu(B), respectively. (iv) The T dependence of the crystal field parameter Dq in the spin-transition region is approximately linear.}, } @article {pmid16832873, year = {2006}, author = {Wigginton, JE and Abecasis, GR}, title = {An evaluation of the replicate pool method: quick estimation of genome-wide linkage peak p-values.}, journal = {Genetic epidemiology}, volume = {30}, number = {4}, pages = {320-332}, doi = {10.1002/gepi.20147}, pmid = {16832873}, issn = {0741-0395}, mesh = {Analysis of Variance ; *Genetic Linkage ; *Genome ; *Models, Genetic ; *Monte Carlo Method ; Proportional Hazards Models ; Statistics, Nonparametric ; }, abstract = {The calculation of empirical p-values for genome-wide non-parametric linkage tests continues to present significant computational challenges for many complex disease mapping studies. The gold standard approach is to use gene dropping to simulate null genome scans. Unfortunately, this approach is too computationally expensive for many data sets of interest. An alternative, more efficient method for sampling null genome scans is to pre-calculate pools of family-specific statistics and then resample from these replicate pools to generate "pseudo-replicate" genome scans. In this study, we use simulations to explore properties of the replicate pool p-value estimator pRP and show that it provides an excellent approximation to the traditional gene-dropping estimator for significantly less computational effort. While the computational efficiency of the replicate pool estimator is noticeable in almost all data sets, by applying the replicate pool method to several previously characterized data sets we show that savings in computational effort can be especially significant (on the order of 10,000-fold or more) when one or more large families are analyzed. We also estimate replicate pool p-values for the schizophrenia data described by Abecasis et al. and show that pRP closely approximates gene-drop p-values for all linkage peaks reported for this study. Lastly, we expand upon Song et al.'s previous work by deriving a conservative estimator of the variance for PRP that can easily be computed in practical settings. We have implemented the replicate pool method along with our variance estimator in a new program called Pseudo, which is the first widely available automated implementation of the replicate pool method.}, } @article {pmid16827547, year = {2005}, author = {Cleveland, DA and Soleri, D and Cuevas, FA and Crossa, J and Gepts, P}, title = {Detecting (trans)gene flow to landraces in centers of crop origin: lessons from the case of maize in Mexico.}, journal = {Environmental biosafety research}, volume = {4}, number = {4}, pages = {197-208; discussion 209-15}, doi = {10.1051/ebr:2006006}, pmid = {16827547}, issn = {1635-7922}, mesh = {Crops, Agricultural/genetics ; Data Interpretation, Statistical ; *Gene Flow ; Mexico ; *Plants, Genetically Modified ; Population Density ; Seeds/genetics ; Zea mays/*genetics ; }, abstract = {There is much discussion of the probability of transgene flow from transgenic crop varieties to landraces and wild relatives in centers of origin or diversity, and its genetic, ecological, and social consequences. Without costly research on the variables determining gene flow, research on transgene frequencies in landrace (or wild relative) populations can be valuable for understanding transgene flow and its effects. Minimal research requirements include (1) understanding how farmer practices and seed systems affect landrace populations, (2) sampling to optimize Ne/n (effective/census population size), (3) minimizing variance at all levels sampled, and (4) using Ne to calculate binomial probabilities for transgene frequencies. A key case is maize in Mexico. Two peer-reviewed papers, based on landrace samples from the Sierra Juárez region of Oaxaca, Mexico, reached seemingly conflicting conclusions: transgenes are present (Quist and Chapela, 2001, Nature 414: 541-543; 2002, Nature 416: 602) or "detectable transgenes" are absent (Ortiz-García et al., 2005, Proc. Natl. Acad. Sci. USA 102: 12338-12343 and 18242). We analyzed these papers using information on Oaxacan maize seed systems and estimates of Ne. We conclude that if Quist and Chapela's results showing presence are accepted, Ortiz-García et al.'s conclusions of no evidence of transgenes at detectable levels or for their introgression into maize landraces in the Sierra de Juárez of Oaxaca are not scientifically justified. This is because their samples are not representative, and their statistical analysis is inconclusive due to using n instead of Ne. Using estimates of Ne based on Ortiz-García et al.'s n, we estimate that transgenes could be present in maize landraces in the Sierra Juárez region at frequencies of approximately 1-4%, and are more likely to be present in the 90% of Oaxacan landrace area that is not mountainous. Thus, we have no scientific evidence of maize transgene presence or absence in recent years in Mexico, Oaxaca State, or the Sierra Juárez region.}, } @article {pmid16825552, year = {2006}, author = {Peacock, E and Garshelis, DL}, title = {Comment on "On the regulation of populations of mammals, birds, fish, and insects" IV.}, journal = {Science (New York, N.Y.)}, volume = {313}, number = {5783}, pages = {45; author reply 45}, doi = {10.1126/science.1127705}, pmid = {16825552}, issn = {1095-9203}, mesh = {Animals ; *Birds/anatomy & histology ; Body Size ; Databases, Factual ; *Fishes/anatomy & histology ; *Insecta/anatomy & histology ; *Mammals/anatomy & histology ; Population Density ; Population Dynamics ; Population Growth ; }, abstract = {Sibly et al.'s (Reports, 22 July 2005, p. 607) contention that density dependence acts strongly on low-density animal populations irrespective of body size contradicts many long-term studies of large mammals. Their findings were distorted by harvest records, which may poorly reflect population trend. Omitting unreliable data, their massive data set is reduced to only one case for large mammals.}, } @article {pmid16770244, year = {2006}, author = {Dresske, B and Haendschke, F and Lenz, P and Ungefroren, H and Jenisch, S and Exner, B and El Mokhtari, NE and Lu, T and Zavazava, N and Faendrich, F}, title = {WOFIE stimulates regulatory T cells: a 2-year follow-up of renal transplant recipients.}, journal = {Transplantation}, volume = {81}, number = {11}, pages = {1549-1557}, doi = {10.1097/01.tp.0000210538.93861.ae}, pmid = {16770244}, issn = {0041-1337}, mesh = {Adolescent ; Adult ; CD4 Antigens/analysis ; Drug Administration Schedule ; Female ; Flow Cytometry ; Follow-Up Studies ; Graft Rejection/drug therapy/immunology ; Humans ; Immune Tolerance/drug effects/*immunology ; Immunosuppressive Agents/*administration & dosage/therapeutic use ; Kidney/immunology/pathology/physiopathology ; Kidney Transplantation/*immunology ; Male ; Middle Aged ; Pilot Projects ; Prospective Studies ; Receptors, Interleukin-2/analysis ; T-Lymphocytes, Regulatory/drug effects/*immunology ; Time Factors ; Transplantation/physiology ; Transplantation Immunology ; Transplantation Tolerance/drug effects/*immunology ; }, abstract = {BACKGROUND: Initial interruption of immunosuppression for 72 hr was analyzed in renal transplant recipients according to Calne et al.'s "window of opportunity for immunologic engagement" (WOFIE) concept.

METHODS: This pilot study was designed as a randomized, open-label, prospective trial of 40 recipients (20 in the WOFIE group, 20 in the control group) of cadaveric kidney transplants who were followed up for 2 years. Immunosuppression comprised tacrolimus (trough levels 5-8 ng/mL), daclizumab (1 mg per kilogram of body weight on day 0 and after 2, 4, 6, and 8 weeks), mycophenolate mofetil (1-2 g/day), and prednisolone (maintenance dose of 10 mg/day). After induction with daclizumab, prednisolone, and mycophenolate mofetil, immunosuppression was interrupted for 72 hr in the WOFIE group. Steroid withdrawal followed in both groups within 12 to 16 weeks posttransplant.

RESULTS: Patient and graft survival did not differ significantly between the two cohorts. However, the WOFIE group experienced less acute rejection episodes and developed better graft function. Although all but one of the patients in the WOFIE group successfully discontinued steroid treatment, permanent steroid withdrawal was achieved in only 76.4% of the control group. After daclizumab discontinuation, the WOFIE group demonstrated an increase of CD4CD25 T cells in peripheral blood (P<0.05 vs. control group), which was stable over time and strongly correlated with a significantly higher expression level of Foxp3-mRNA.

CONCLUSIONS: Initial interruption of immunosuppression for 72 hr correlates with the induction of regulatory immunologic mechanisms and allows early and reliable minimization of immunosuppressive treatment.}, } @article {pmid16730247, year = {2006}, author = {Basaranoglu, M and Demirkok, SS and Coker, E}, title = {Considerations in seasonal variation studies in IBD and re-evaluation of Aratari et al.'s seasonality results.}, journal = {Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver}, volume = {38}, number = {9}, pages = {710-1; author reply 711}, doi = {10.1016/j.dld.2006.04.004}, pmid = {16730247}, issn = {1590-8658}, mesh = {*Data Interpretation, Statistical ; Humans ; Irritable Bowel Syndrome/*epidemiology ; Research Design ; *Seasons ; }, } @article {pmid16719656, year = {2006}, author = {Bonatti, LL and Peña, M and Nespor, M and Mehler, J}, title = {How to hit Scylla without avoiding Charybdis: comment on Perruchet, Tyler, Galland, and Peereman (2004).}, journal = {Journal of experimental psychology. General}, volume = {135}, number = {2}, pages = {314-21; discussion 322-6}, doi = {10.1037/0096-3445.135.2.314}, pmid = {16719656}, issn = {0096-3445}, mesh = {Adult ; Generalization, Psychological ; Humans ; Infant ; *Language Development ; *Learning ; Psycholinguistics ; *Speech Perception ; *Statistics as Topic ; }, abstract = {M. Peña, L. L. Bonatti, M. Nespor, and J. Mehler argued that humans compute nonadjacent statistical relations among syllables in a continuous artificial speech stream to extract words, but they use other computations to determine the structural properties of words. Instead, when participants are familiarized with a segmented stream, structural generalizations about words are quickly established. P. Perruchet, M. D. Tyler, N. Galland, and R. Peereman criticized M. Peña et al.'s work and dismissed their results. In this article, the authors show that P. Perruchet et al.'s criticisms are groundless.}, } @article {pmid16718581, year = {2006}, author = {Vrij, A and Mann, S and Fisher, RP}, title = {An empirical test of the behaviour analysis interview.}, journal = {Law and human behavior}, volume = {30}, number = {3}, pages = {329-345}, doi = {10.1007/s10979-006-9014-3}, pmid = {16718581}, issn = {0147-7307}, mesh = {Adolescent ; Adult ; *Deception ; *Empirical Research ; Female ; Humans ; *Interview, Psychological ; Male ; Middle Aged ; *Signal Detection, Psychological ; *Social Behavior ; }, abstract = {The present experiment is the first empirical test of the Behaviour Analysis Interview (BAI), an interview technique developed by F. E. Inbau, J. E. Reid, J. P. Buckley, & B. C. Jayne (2001) designed to evoke different verbal and non-verbal responses from liars and truth-tellers. Inbau et al. expect liars to be less helpful than truth-tellers in investigations and to exhibit more nervous behaviours. Just the opposite predictions, however, follow from the deception literature, which notes that liars take their credibility less for granted and are therefore more aware of their responses and their impact on others. This suggests that liars' answers should be more helpful than truth-tellers' answers, and liars' non-verbal responses should appear more relaxed than truth-tellers' non-verbal responses. In the present experiment, 40 participants (undergraduate students) lied or told the truth about an event during a BAI interview. The interviews were coded according to Inbau et al.'s guidelines. The results showed that, compared to liars, truth-tellers (a) were more naive and evasive when explaining the purpose of the interview, and (b) were less likely to name someone who they felt certain did not commit the crime. Truth-tellers also exhibited more nervous behaviours. The results were consistent with the predictions of the deception literature, and directly opposed to the predictions of BAI.}, } @article {pmid16707263, year = {2007}, author = {Smilek, D and Eastwood, JD and Reynolds, MG and Kingstone, A}, title = {Metacognitive errors in change detection: missing the gap between lab and life.}, journal = {Consciousness and cognition}, volume = {16}, number = {1}, pages = {52-7; discussion 58-62}, doi = {10.1016/j.concog.2006.04.001}, pmid = {16707263}, issn = {1053-8100}, mesh = {*Cognition ; Humans ; *Laboratories ; *Signal Detection, Psychological ; Surveys and Questionnaires ; Visual Perception ; }, abstract = {Studies of change detection suggest that people tend to overestimate their ability to detect visual changes. In a recent laboratory study of change detection and human intention, Beck et al., found that individuals have an inadequate understanding that intention can improve change detection performance and that its importance increases with scene complexity. We note that these findings may be specific to unfamiliar situations such as those generated routinely in studies of change detection. In two questionnaire studies, we demonstrate that when participants consider real world scenarios such as driving, people are well aware that the intention to detect changes improves detection performance, especially in complex scenes. We suggest several reasons why change detection findings like Beck et al.'s do not generalize to real world situations. More broadly, we suggest a possible way to bridge the gap between lab and life.}, } @article {pmid16700055, year = {2006}, author = {Müller, H}, title = {Ontogeny of the skull, lower jaw, and hyobranchial skeleton of Hypogeophis rostratus (Amphibia: Gymnophiona: Caeciliidae) revisited.}, journal = {Journal of morphology}, volume = {267}, number = {8}, pages = {968-986}, doi = {10.1002/jmor.10454}, pmid = {16700055}, issn = {0362-2525}, mesh = {Amphibians/anatomy & histology/*embryology ; Animals ; Branchial Region/anatomy & histology/*embryology/ultrastructure ; Mandible/anatomy & histology/*embryology/ultrastructure ; Skull/anatomy & histology/embryology/ultrastructure ; }, abstract = {Few detailed descriptions of the development of the head skeleton in caecilian amphibians are available. One of those is the work of Marcus and students (e.g., Gehwolf [1923] Z Anat Entwick 68:433-454; Marcus [1933] Anat Anz 80:142-146; Marcus et al. [1935] Gegenbaurs Morphol Jb 76:375-420) on the morphology and development of the skull, lower jaw, and hyobranchial skeleton in the Seychellean caeciliids Hypogeophis rostratus and Grandisonia alternans. These workers described a high number of individual ossifications that fuse during ontogeny to form the adult skull. Although later studies have doubted the generality of those observations, the work of Marcus and his students has been hugely influential in subsequent studies of caecilian skull morphology and amphibian evolution. Based on new observations on an ontogenetic series of 32 sectioned and cleared and stained specimens, ranging from the beginning of chondrification to the adult, the development of the skull, lower jaw, and hyobranchial skeleton of H. rostratus are described. The new results are largely incompatible with those of Marcus and students and no evidence for several of the reported ossifications, including supra-, infra-, and basioccipital, epiotic, pleurosphenoid, preethmoid, posterior vomer, prepalatine, quadratojugal, postparietal, second coronoid, supraangular, and complementare, is found. It is argued that most of Marcus et al.'s reports of nonexistent ossifications are based on false phylogenetic preconception, misinterpretation of the observed morphology, and technical error. Data on the ossification sequence of the skull and lower jaw in H. rostratus are provided and briefly compared to published information on Dermophis mexicanus and Gegeneophis ramaswamii.}, } @article {pmid16696843, year = {2006}, author = {Juujärvi, S}, title = {The ethic of care development: a longitudinal study of moral reasoning among practical-nursing, social-work and law-enforcement students.}, journal = {Scandinavian journal of psychology}, volume = {47}, number = {3}, pages = {193-202}, doi = {10.1111/j.1467-9450.2006.00507.x}, pmid = {16696843}, issn = {0036-5564}, mesh = {Adult ; Analysis of Variance ; *Education, Professional ; *Empathy ; Female ; Finland ; Humans ; Longitudinal Studies ; Male ; *Moral Development ; Nursing, Practical/education ; Police/education ; Psychological Theory ; Regression Analysis ; *Social Justice ; Social Work/education ; }, abstract = {The study investigated changes in care-based moral reasoning, in the context of justice development over the 2-year period among practical-nursing, bachelor-degree social-work and law-enforcement students (N = 59). Main measures were Skoe's Ethic of Care Interview and Colby et al.'s Moral Judgment Interview. Of the participants 34% progressed in care reasoning, and 48% in justice reasoning. Social-work and nursing students progressed in care reasoning, and all groups progressed in justice reasoning. One participant (1.7%) regressed in care reasoning. Care and justice reasoning were parallel in terms of internal consistency, and they were positively related to each other. Findings suggest that care reasoning follows a developmental sequence, involving three main and two transitional levels, as suggested by Gilligan (1982). Main levels include self-concern (Level 1), caring for others (Level 2), and balanced caring for self and others (Level 3).}, } @article {pmid16688593, year = {2006}, author = {De Dominicis, L and Cardinali, P and Pucci, E and Marchegiani, G and Caporalini, R and Moretti, V and Sanguigni, S and Carle, F and Gesuita, R and Giuliani, G}, title = {What do Italians at high risk of stroke know about ischaemic stroke? A survey among a group of subjects undergoing neuro-sonographic examination.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {27}, number = {1}, pages = {7-13}, doi = {10.1007/s10072-006-0558-2}, pmid = {16688593}, issn = {1590-1874}, mesh = {Aged ; Awareness ; Brain Ischemia/diagnostic imaging/*epidemiology ; Community-Institutional Relations/*trends ; Emergency Service, Hospital/statistics & numerical data/trends ; Female ; Health Services Accessibility/statistics & numerical data/trends ; Humans ; Male ; Middle Aged ; Patient Education as Topic/statistics & numerical data/*trends ; Risk Factors ; Stroke/diagnostic imaging/*epidemiology ; *Surveys and Questionnaires ; Ultrasonography ; }, abstract = {The objective was to assess the knowledge about ischaemic stroke among selected groups of persons at high risk for stroke. Outpatients referred to 3 hospital ultrasound departments in the Marche Region (Italy) were asked to answer a questionnaire. Data were collected on: (1) demographic characteristics; (2) risk profile determined using Coppola et al.'s scoring system; (3) knowledge about symptoms, risk factors, part of the body injured and best referral option for stroke. Of the 352 respondents, around 52% were unable to report even one warning symptom of stroke, while 58.4% of participants at increased risk did not know any risk factors. Only 64.5% identified the brain as the part of the body injured by stroke. Only 59.4% considered the Emergency Department as the best referral option in the event of stroke. This study confirms poor knowledge about stroke in our study population, particularly in subjects with increased stroke risk.}, } @article {pmid16686112, year = {2006}, author = {Singer, M and Wixted, JT}, title = {Effect of delay on recognition decisions: evidence for a criterion shift.}, journal = {Memory & cognition}, volume = {34}, number = {1}, pages = {125-137}, pmid = {16686112}, issn = {0090-502X}, mesh = {Adolescent ; Adult ; Association Learning ; Attention ; *Decision Making ; Discrimination Learning ; Female ; Humans ; Inhibition, Psychological ; Male ; Memory, Short-Term ; *Mental Recall ; Problem Solving ; *Reading ; *Retention, Psychology ; Semantics ; *Verbal Learning ; }, abstract = {Recent evidence indicates that in intermixed recognition testing of different stimulus classes, people can apply different decision criteria (a criterion shift) to stimulus classes distinguished by the study-test delay (Singer, Gagnon, & Richards, 2002), but not by a conspicuous strength manipulation (Stretch & Wixted, 1998b). In an attempt to reconcile these differences, we applied Singer et al.'s text retrieval method to word recognition. People first studied blocked items from each of five categories. After a delay, five new category lists were presented. After each one, the participants recognized intermixed targets and distractors from the current category and one of the earlier ones. At delays of up to 40 min, the answering criteria for immediate and delayed categories were indistinguishable. At delays of 2 days, in contrast, however, both yes-no and confidence-rating data indicated that more lenient criteria were applied to delayed than to immediate test items. This suggests that people can use the delay between study and test to flexibly adjust the decision criteria of word recognition.}, } @article {pmid16683499, year = {2006}, author = {Jansari, AS and Spiller, MJ and Redfern, S}, title = {Number synaesthesia: when hearing "four plus five" looks like gold.}, journal = {Cortex; a journal devoted to the study of the nervous system and behavior}, volume = {42}, number = {2}, pages = {253-258}, doi = {10.1016/s0010-9452(08)70350-2}, pmid = {16683499}, issn = {0010-9452}, mesh = {Adult ; Attention ; Awareness ; *Color Perception ; Female ; Humans ; Male ; *Mathematics ; Middle Aged ; *Pattern Recognition, Visual ; *Problem Solving ; Psychophysics ; Reference Values ; *Speech Perception ; }, abstract = {Whilst lexical-colour synaesthesia has been widely studied, the number-colour pairing has received relatively less attention. Since one very strong variable is the structure and "ordinality" within a set of inducers (e.g., letters of the alphabet, days of the week and months of the year), the inherent hierarchy of numbers suggests that number-synaesthesia should be found in most synaesthetes. Three synaesthetes were recruited who showed between 80 and 100% consistency of synaesthetic responses to a set of stimuli across a three month interval. Their synaesthesia for numbers was investigated using an extension of Dixon et al.'s (2000) "2 plus 5 equals yellow" paradigm. Participants saw single digits and operators for an arithmetic process followed by a coloured square which was either congruent or incongruent with their individual colour for the answer; the task was to name the colour followed by stating the solution to the arithmetic sum. To see whether number-processing synaesthesia extends beyond the visual domain into the auditory domain the same procedure was used with the digits and operators being presented aurally. Relative to age-matched controls congruency effects were found for the synaesthetes. These findings add to the suggestion that synaesthesia can occur at a conceptual level where physical experience of an inducer is not necessary. Additionally, the findings showed that for one synaesthete there was a statistical difference in the auditory but not visual condition whilst for the remaining two synaesthetes, the reverse pattern was observed. This variable pattern adds to the body of literature that further illustrates the heterogeneity of synaesthesia. The findings are incorporated into Rich and Mattingley's (2002) neurocognitive model of synaesthesia and observations which cannot yet be explained are highlighted as future directions for research.}, } @article {pmid16676019, year = {2006}, author = {Loescher, LJ and Harris, RB and Lim, KH and Su, Y}, title = {Thorough skin self-examination in patients with melanoma.}, journal = {Oncology nursing forum}, volume = {33}, number = {3}, pages = {633-637}, doi = {10.1188/06.ONF.633-637}, pmid = {16676019}, issn = {1538-0688}, support = {P30CA023074/CA/NCI NIH HHS/United States ; R25CA078447/CA/NCI NIH HHS/United States ; }, mesh = {Aged ; Cross-Sectional Studies ; Feasibility Studies ; Female ; Humans ; Male ; Melanoma/*diagnosis ; *Self-Examination ; Skin Neoplasms/*diagnosis ; }, abstract = {PURPOSE/OBJECTIVES: To examine the feasibility of using Weinstock et al.'s thorough skin self-examination (TSSE) assessment in patients with melanoma, to describe TSSE characteristics of patients with melanoma, and to explore associations of personal and disease variables with TSSE.

DESIGN: Cross-sectional, descriptive feasibility study; part of a larger study of melanoma in families.

SETTING: Outpatient melanoma clinics in a National Cancer Institute-designated comprehensive cancer center.

SAMPLE: Purposive sample of 70 predominantly white participants (47% women, 53% men), with a mean age of 65 years (SD = 11 years) and pathologically confirmed cutaneous melanoma (any stage).

METHODS: Weinstock et al.'s TSSE assessment (self-report of the number of times patients examined the surface of seven specific body areas during the prior two months) and items regarding partnered TSSE and skin examination from healthcare providers.

MAIN RESEARCH VARIABLES: Frequency of TSSE and healthcare provider skin examination, partnered TSSE, and reasons for not performing TSSE.

FINDINGS: Forty-one (59%) participants reported performing TSSE; by Weinstock et al.'s criteria, only 23 (33%) practiced TSSE. Use of a partner was significantly associated with TSSE (p = 0.001); patients indicated high rates of skin examination by healthcare providers.

CONCLUSIONS: Patients with melanoma are at high risk for recurrent disease. TSSE contributes to early detection of melanoma. Although Weinstock et al.'s TSSE assessment is feasible for use among patients with melanoma in a clinical setting, the focus should be on examination of specific body areas, rather than global skin examination. Overall, patients with melanoma had a low frequency of TSSE; however, data regarding previous knowledge or instruction of TSSE were not collected. Involving a partner enhances the frequency of TSSE.

IMPLICATIONS FOR NURSING: Patients with melanoma should be informed of the importance of conducting systematic TSSE and using a partner during examination; however, some patients may prefer skin examination by healthcare providers. Measurement of TSSE self-report merits further study.}, } @article {pmid16673825, year = {2006}, author = {Grace, RC and McLean, AP}, title = {Rapid acquisition in concurrent chains: evidence for a decision model.}, journal = {Journal of the experimental analysis of behavior}, volume = {85}, number = {2}, pages = {181-202}, pmid = {16673825}, issn = {0022-5002}, mesh = {Animals ; *Choice Behavior ; Columbidae ; *Conditioning, Psychological ; *Decision Making ; Discrimination Learning ; *Reinforcement, Psychology ; }, abstract = {Pigeons' choice in concurrent chains can adapt to rapidly changing contingencies. Grace, Bragason, and McLean (2003) found that relative initial-link response rate was sensitive to the immediacy ratio in the current session when one of the terminal-link fixed-interval schedules was changed daily according to a pseudorandom binary sequence (e.g., Schofield & Davison, 1997). The present experiment tested whether the degree of variation in delays across sessions had any effect on acquisition rate in Grace et al.'s (2003) rapid-acquisition procedure. In one condition ("minimal variation"), the left terminal link was always fixed-interval 8 s and the right terminal link was either fixed-interval 4 s or fixed-interval 16 s. In the other condition ("maximal variation"), a unique pair of fixed-interval values was used in each session. Responding was sensitive to the current-session immediacy ratio in both conditions, but across subjects there was no systematic difference in sensitivity. These results challenge the view that initial-link responding in the rapid-acquisition procedure is determined by changes in the learned value of the terminal-link stimuli, and suggests instead that a process resembling categorical discrimination may control performance. A decision model based on the assumption that delays are categorized as short or long relative to the history of delays provided a good account of the data and shows promise in being able to explain other choice phenomena.}, } @article {pmid16612383, year = {2006}, author = {Wooding, S and Bufe, B and Grassi, C and Howard, MT and Stone, AC and Vazquez, M and Dunn, DM and Meyerhof, W and Weiss, RB and Bamshad, MJ}, title = {Independent evolution of bitter-taste sensitivity in humans and chimpanzees.}, journal = {Nature}, volume = {440}, number = {7086}, pages = {930-934}, doi = {10.1038/nature04655}, pmid = {16612383}, issn = {1476-4687}, mesh = {Alleles ; Animals ; Base Sequence ; *Biological Evolution ; Genotype ; Gorilla gorilla/genetics/physiology ; Humans ; Pan troglodytes/*genetics/*physiology ; Phenotype ; Phenylthiourea/*pharmacology ; Receptors, Cell Surface/genetics/metabolism ; Receptors, G-Protein-Coupled ; Taste/drug effects/*physiology ; Taste Receptors, Type 2 ; }, abstract = {It was reported over 65 years ago that chimpanzees, like humans, vary in taste sensitivity to the bitter compound phenylthiocarbamide (PTC). This was suggested to be the result of a shared balanced polymorphism, defining the first, and now classic, example of the effects of balancing selection in great apes. In humans, variable PTC sensitivity is largely controlled by the segregation of two common alleles at the TAS2R38 locus, which encode receptor variants with different ligand affinities. Here we show that PTC taste sensitivity in chimpanzees is also controlled by two common alleles of TAS2R38; however, neither of these alleles is shared with humans. Instead, a mutation of the initiation codon results in the use of an alternative downstream start codon and production of a truncated receptor variant that fails to respond to PTC in vitro. Association testing of PTC sensitivity in a cohort of captive chimpanzees confirmed that chimpanzee TAS2R38 genotype accurately predicts taster status in vivo. Therefore, although Fisher et al.'s observations were accurate, their explanation was wrong. Humans and chimpanzees share variable taste sensitivity to bitter compounds mediated by PTC receptor variants, but the molecular basis of this variation has arisen twice, independently, in the two species.}, } @article {pmid16597579, year = {2006}, author = {Zhang, AY and Harmon, JA and Werkner, J and McCormick, RA}, title = {The long-term relationships between the motivation for change and alcohol use severity among patients with severe and persistent mental illness.}, journal = {Journal of addictive diseases}, volume = {25}, number = {1}, pages = {121-128}, doi = {10.1300/J069v25n01_14}, pmid = {16597579}, issn = {1055-0887}, mesh = {Adult ; Aged ; Aged, 80 and over ; Alcoholism/*epidemiology/therapy ; Bipolar Disorder/*epidemiology ; Diagnosis, Dual (Psychiatry) ; Female ; Humans ; Male ; Middle Aged ; *Motivation ; Ohio/epidemiology ; Schizophrenia/*epidemiology ; Severity of Illness Index ; Veterans ; }, abstract = {This study examined the long-term relationship of changes in the motivation to remedy alcohol abuse to alcohol use severity among patients with a dual diagnosis of substance abuse disorder and severe and persistent mental illness. Linear regression analyses showed that patients who increasingly recognized alcohol use problems over a 9-month period exhibited significantly greater alcohol use severity at 9 months and a significant increase in alcohol use severity over time. Moreover, patients who became increasingly determined to take actions against alcohol use over a 9-month period exhibited significantly lower alcohol use severity at 9 months and a significant decrease in alcohol use severity over time. The findings support Prochaska et al.'s transtheoretical model of the motivation for change. They suggest that the recognition of alcohol use problems comes along with learning adverse consequences of alcohol use and that increased determination to take actions is critical to the long-term behavioral changes in alcohol use.}, } @article {pmid16596723, year = {2006}, author = {Ping, C and Lin, Z and Jiming, D and Jin, Z and Ying, L and Shigang, D and Hongtao, Y and Yongwei, H and Jiahong, D}, title = {The phosphoinositide 3-kinase/Akt-signal pathway mediates proliferation and secretory function of hepatic sinusoidal endothelial cells in rats after partial hepatectomy.}, journal = {Biochemical and biophysical research communications}, volume = {342}, number = {3}, pages = {887-893}, doi = {10.1016/j.bbrc.2006.02.034}, pmid = {16596723}, issn = {0006-291X}, mesh = {Animals ; Cell Cycle ; Cell Proliferation ; Endothelial Cells/cytology/*metabolism ; *Hepatectomy ; Hepatocyte Growth Factor/metabolism ; Hepatocytes/*cytology/*metabolism ; Interleukin-6/metabolism ; Male ; NF-kappa B/metabolism ; Nitric Oxide/metabolism ; Nitric Oxide Synthase/metabolism ; Phosphatidylinositol 3-Kinases/*metabolism ; Proto-Oncogene Proteins c-akt/*metabolism ; Rats ; Rats, Wistar ; *Signal Transduction ; Thymidine/metabolism ; Tritium/metabolism ; }, abstract = {OBJECTIVE: To investigate the role of AKT signaling pathway in hepatic sinusoidal endothelial cells (SECs) early after partial hepatectomy in rats and the regulatory mechanisms involved.

METHODS: The animal model of 70% hepatectomy was made. Hepatic SECs were isolated and cultured according to Braet et al.'s method with some modifications. The cultured hepatic SECs were divided into two groups: 70% partial hepatectomy groups and LY294002 group (LY). We observed the expressions of AKT and NF-kappaB in cultured hepatic SECs by Western blot, measured the levels of NO, NOs, IL-6, and HGF in the supernatants of hepatic SEC cultures and [3H]thymidine incorporation, and analyzed cell cycle of cultured hepatic SECs by flow cytometer. The relationship of the Akt pathway with secretions and proliferation of hepatic SECs after partial hepatectomy was probed.

RESULTS: The levels of Akt protein expression increased significantly after partial hepatectomy in OG group and with a peak at 24 h post operation. Meanwhile, there was a markedly increase in phosphorylated Akt protein during 2-72 h after operation. But the expression and activity of Akt protein did not change significantly after partial hepatectomy in the LY group. So, partial hepatectomy can marked induce Akt expression and result in rapid and marked phosphorylation of Akt from 2 to 72 h thereafter. The changes of NF-kappaB expression in cultured hepatic SECs were similar to those of Akt expression after operation. The concentrations of HGF and IL-6 in the supernatants of cultured hepatic SECs were relatively low in the LY group, and were markedly increased after partial hepatectomy, with a peak at 24 h in the OG group. There were significant differences between the OG and LY groups at 6 and 24 h (P < 0.05). Both NO and NOS secretion was increased in the OG group compared to the LY group within 24 h after partial hepatectomy. But the secretion of NO and NOS was increased more markedly in the LY group than that in the OG beyond 24 h. These findings suggest that the secretion of the cytokines by hepatic SECs is mediated by Akt signaling. Akt signaling pathway in relationship with proliferation of hepatic SECs and suppression of apoptosis. In OG group, the hepatic SECs in S and G2/M obviously increased. The proliferative index of hepatic SECs in OG group had significant differences with that in LY group at 6, 24, and 72 h, P < 0.05. Meanwhile, the cells of apoptosis in OG group were very low, and the cells in LY group gradually increased.

CONCLUSIONS: These results suggest that AKT signaling pathway plays a crucial role in mediating proliferating and secreted signals in hepatic SECs. AKT has been suggested to play a pivotal role in early liver regeneration involved in the induction of secreted cytokines and proliferation of hepatic SECs.}, } @article {pmid16594791, year = {2006}, author = {Murphy, DR and Daneman, M and Schneider, BA}, title = {Why do older adults have difficulty following conversations?.}, journal = {Psychology and aging}, volume = {21}, number = {1}, pages = {49-61}, doi = {10.1037/0882-7974.21.1.49}, pmid = {16594791}, issn = {0882-7974}, mesh = {Adult ; Aged ; Aging/*physiology ; Cognition Disorders/epidemiology ; *Communication ; Female ; Hearing Disorders/*epidemiology ; Humans ; Male ; *Speech Perception ; }, abstract = {Age-related declines in understanding conversation may be largely a consequence of perceptual rather than cognitive declines. B. A. Schneider, M. Daneman, D. R. Murphy, and S. Kwong-See (2000) showed that age-related declines in comprehending single-talker discourse could be eliminated when adjustments were made to compensate for the poorer hearing of older adults. The authors used B. A. Schneider et al.'s methodology to investigate age-related differences in comprehending 2-person conversations. Compensating for hearing difficulties did not eliminate age-related differences when the 2 talkers were spatially separated by 9 degrees or 45 degrees azimuth, but it did when the talkers' contributions came from one central location. These findings suggest that dialogue poses more of a problem for older than for younger adults, not because of the additional cognitive requirements of having to follow 2 talkers rather than 1, but because older adults are not as good as younger adults at making use of the auditory cues that are available for helping listeners perceptually segregate the contributions of 2 spatially separated talkers.}, } @article {pmid16586101, year = {2007}, author = {Koenig, CS and Platt, RD and Griggs, RA}, title = {Using dual-process theory and analogical transfer to explain facilitation on a hypothetico-deductive reasoning task.}, journal = {Psychological research}, volume = {71}, number = {4}, pages = {495-502}, pmid = {16586101}, issn = {0340-0727}, mesh = {Adult ; *Cognition ; *Decision Making ; Humans ; *Psychological Theory ; *Transfer, Psychology ; }, abstract = {Using the analogical transfer paradigm, the present study investigated the competing explanations of Girotto and Legrenzi (Psychological Research 51: 129-135, 1993) and Griggs, Platt, Newstead, and Jackson (Thinking and Reasoning 4: 1-14, 1998) for facilitation on the SARS version of the THOG problem, a hypothetico-deductive reasoning task. Girotto and Legrenzi argue that facilitation is based on logical analysis of the task [System 2 reasoning in Evans's (Trends in Cognitive Sciences 7: 454-459, 2003) dual-process account of reasoning] while Griggs et al. maintain that facilitation is due to an attentional heuristic produced by the wording of the problem (System 1 reasoning). If Girotto and Legrenzi are correct, then System 2 reasoning, which is volitional and responsible for deductive reasoning, should be elicited, and participants should comprehend the solution principle of the THOG task and exhibit analogical transfer. However, if Griggs et al. are correct, then System 1 reasoning, which is responsible for heuristic problem solving strategies such as an attentional heuristic, should occur, and participants should not abstract the solution principle and transfer should not occur. Significant facilitation (68 and 82% correct) was only observed for the two SARS source problems, but significant analogical transfer did not occur. This lack of transfer suggests that System 1 reasoning was responsible for the facilitation observed in the SARS problem, supporting Griggs et al.'s attentional heuristic explanation. The present results also underscore the explanatory value of using analogical transfer rather than facilitation as the criterion for problem understanding.}, } @article {pmid16569159, year = {2006}, author = {Franco-Watkins, AM and Pashler, H and Rickard, TC}, title = {Does working memory load lead to greater impulsivity? Commentary on Hinson, Jameson, and Whitney (2003).}, journal = {Journal of experimental psychology. Learning, memory, and cognition}, volume = {32}, number = {2}, pages = {443-7; discussion 448-50}, doi = {10.1037/0278-7393.32.2.443}, pmid = {16569159}, issn = {0278-7393}, mesh = {Decision Making ; Humans ; Impulsive Behavior/*psychology ; Memory, Short-Term/*physiology ; *Mental Recall ; Models, Psychological ; }, abstract = {Previous research by J. M. Hinson, T. L. Jameson, and P. Whitney (2003) demonstrated that a secondary task in a delayed discounting paradigm increased subjects' preference for the immediate reward. J. M. Hinson et al. interpreted their findings as evidence that working memory load results in greater impulsivity. The present authors conducted a reanalysis of the data from J. M. Hinson et al.'s Experiment 1 at the individual-subject level. Difference scores were calculated by subtracting the digit memory load condition from the control condition for k (discounting parameter) and a measure of "erroneous" responses. The results indicated that the secondary task increased random responding, which in turn can account for the increased mean estimates of k. Thus, the data do not support the claim that cognitive load affects impulsivity per se.}, } @article {pmid16569141, year = {2006}, author = {Oberauer, K}, title = {Is the focus of attention in working memory expanded through practice?.}, journal = {Journal of experimental psychology. Learning, memory, and cognition}, volume = {32}, number = {2}, pages = {197-214}, doi = {10.1037/0278-7393.32.2.197}, pmid = {16569141}, issn = {0278-7393}, mesh = {Analysis of Variance ; Attention/*physiology ; Humans ; Memory, Short-Term/*physiology ; Neuropsychological Tests ; *Practice, Psychological ; Reaction Time ; Time Factors ; }, abstract = {This article reinvestigates the claim by P. Verhaeghen, J. Cerella, and C. Basak (2004) that the focus of attention in working memory can be expanded from 1 to 4 items through practice. Using a modified version of Verhaeghen et al.'s n-back paradigm, Experiments 1 and 3 show that a signature of a one-item focus, the time cost for switching between items in working memory, persists over practice. Verhaeghen et al. reported a shift over practice from a step function to a linear slope of reaction times over set size and argued that it reflects the expansion of the focus. With an improved counterbalancing scheme, a continuously increasing slope was found even without practice in Experiment 2. The results question the hypothesis that the focus is expanded through practice. They are in line with predictions from a model that distinguishes a one-item focus from a direct-access region holding about 4 items.}, } @article {pmid16553998, year = {2006}, author = {Gyekye, SA}, title = {Workers' perceptions of workplace safety: an African perspective.}, journal = {International journal of occupational safety and ergonomics : JOSE}, volume = {12}, number = {1}, pages = {31-42}, doi = {10.1080/10803548.2006.11076667}, pmid = {16553998}, issn = {1080-3548}, mesh = {Adolescent ; Adult ; Africa ; *Attitude ; Employment/*psychology ; Female ; Humans ; Interviews as Topic ; Job Satisfaction ; Male ; Middle Aged ; *Occupational Health ; }, abstract = {This study investigated workers' perceptions of workplace safety in an African work environment, specifically in Ghanaian work places. Workers' safety perceptions were examined with Hayes et al.'s. (1998) Work Safety Scale. Comparative analyses were done between high- and low-accident groups, and t tests were employed to test for differences of statistical significance. Relative to their colleagues in the low-accident category, workers in the high-accident category exhibited negative perceptions on safety. They had negative perceptions regarding work safety, safety programmes, supervisors, and co-workers' contributions. Besides, they expressed less job satisfaction and were less committed to safety management policies. Perceptions regarding management's attitude towards safety between the 2 groups were not of statistical significance. The analyses provided an explanation for the cause of a substantial portion of the high rate of industrial accidents in Ghana's work environment. Implications for safety management are discussed.}, } @article {pmid16551168, year = {2006}, author = {Silberberg, A and Roma, PG and Ruggiero, AM and Suomi, SJ}, title = {On inequity aversion in nonhuman primates.}, journal = {Journal of comparative psychology (Washington, D.C. : 1983)}, volume = {120}, number = {1}, pages = {76}, doi = {10.1037/0735-7036.120.1.76}, pmid = {16551168}, issn = {0735-7036}, mesh = {Animals ; *Avoidance Learning ; *Behavior, Animal ; Frustration ; Primates ; Psychological Theory ; *Social Behavior ; }, abstract = {P. G. Roma, A. Silberberg, A. M. Ruggiero, and S. J. Suomi (2006) noted that the results S. F. Brosnan and F. B. M. de Waal (2003) attributed to inequity aversion could also be explained as a frustration effect. Roma et al. redressed this confound by designing a procedure that could have supported either of these interpretations. Nevertheless, they found that only a frustration effect accounted for both their data and those of Brosnan and de Waal (2003). The criticisms Brosnan and de Waal (2006) offered of Roma et al. ignored the fact that Brosnan and de Waal's (2003) research design was not capable of offering an unequivocal demonstration of inequity aversion. This conclusion holds no matter what the claimed inadequacies of Roma et al.'s procedures might have been. Caution is urged in inferring the existence of inequity aversion in nonhuman primates.}, } @article {pmid16551167, year = {2006}, author = {Brosnan, SF and de Waal, FB}, title = {Partial support from a non-replication: comment on Roma, Silberberg, Ruggiero, and Suomi (2006).}, journal = {Journal of comparative psychology (Washington, D.C. : 1983)}, volume = {120}, number = {1}, pages = {74-75}, doi = {10.1037/0735-7036.120.1.74}, pmid = {16551167}, issn = {0735-7036}, mesh = {Animals ; *Behavior, Animal ; Cebus ; *Frustration ; Social Behavior ; }, abstract = {A purported replication by P. G. Roma, A. Silberberg, A. M. Ruggiero, and S. J. Suomi of the authors' previous study claims to contradict their finding that capuchin monkeys (Cebus apella) refuse to exchange with an experimenter if their partner receives a superior reward. Roma et al. used no exchange task, however, or any other task. Roma et al. offered frustration as explanation of their findings, yet failed to statistically prove that the effect of frustration is stronger than that of inequity. They also misrepresented the dependent measure of the authors' study. Reanalysis of the authors' own data indicated no role of frustration, that is, no effect of previous experience with a superior reward. The authors conclude that Roma et al.'s study is not a replication and does not disprove the authors' findings.}, } @article {pmid16530998, year = {2006}, author = {Dhanjal, KS and Bhardwaj, MK and Liversidge, HM}, title = {Reproducibility of radiographic stage assessment of third molars.}, journal = {Forensic science international}, volume = {159 Suppl 1}, number = {}, pages = {S74-7}, doi = {10.1016/j.forsciint.2006.02.020}, pmid = {16530998}, issn = {0379-0738}, mesh = {Adolescent ; Adult ; Age Determination by Teeth/*methods ; Child ; Forensic Dentistry/methods ; Humans ; Molar, Third/*diagnostic imaging/*growth & development ; Radiography, Panoramic ; Reproducibility of Results ; }, abstract = {UNLABELLED: The aim of this study was to determine intra- and inter-observer variability of the developing third molar from panoramic radiographs. Formation of third molars was assessed according to stages described by modified Demirjian et al.'s methods: Moorrees et al. [C.F.A. Moorrees, E.A. Fanning, E.E. Hunt, Age variation of formation stages for ten permanent teeth, J. Dent. Res. 42 (1963) 1490-1502] and Solari and Abramovitch [A.C. Solari, K. Abramovitch, The accuracy and precision of third molar development as an indicator of chronological age in Hispanics, J. Forensic Sci. 47 (2002) 531-535]; in addition, data were also analysed unmodified, i.e. Haavikko [K. Haavikko, The formation and alveolar and clinical eruption of the permanent teeth, an orthopantomograph study, Proc. Finn. Dent. Soc. 66 (1970) 104-170] and Demirjian et al. [A. Demirjian, H. Goldstein, J.M. Tanner, A new system of dental age assessment, Hum. Biol. 45 (1973) 211-227]. The sample was a random selection of 73 panoramic radiographs from patients aged 8-24 years. After training, the left maxillary and mandibular third molars were scored on two separate occasions without knowledge of previous scores. Cohen's Kappa and percentage agreement were calculated for each method, for maxillary, for mandibular third molars and combined. Percentage agreement for stages was also calculated. Intra-observer agreement was greater for mandibular third molars compared to maxillary third molars, and better for methods with fewer stages. Kappa values indicated good agreement for most methods; the best was Demirjian et al.'s method for mandibular third molar with very good agreement (K = 0.80) for the first author, good agreement for the second author (K = 0.75) and good agreement between observers (K = 0.75). The stages with best agreement were Demirjian's stage E [A. Demirjian, H. Goldstein, J.M. Tanner, A new system of dental age assessment, Hum. Biol. 45 (1973) 211-227] and Moorrees et al.'s stage Cc and R1/4 [C.F.A. Moorrees, E.A. Fanning, E.E. Hunt, Age variation of formation stages for ten permanent teeth, J. Dent. Res. 42 (1963) 1490-1502].

CONCLUSIONS: Having clearly defined stages and fewer stages allowed better reproducibility of third molar formation.}, } @article {pmid16526475, year = {2006}, author = {Tsang, IW and Kwok, JT}, title = {Efficient hyperkernel learning using second-order cone programming.}, journal = {IEEE transactions on neural networks}, volume = {17}, number = {1}, pages = {48-58}, doi = {10.1109/TNN.2005.860848}, pmid = {16526475}, issn = {1045-9227}, mesh = {Algorithms ; *Artificial Intelligence ; Data Interpretation, Statistical ; Disease/classification ; Normal Distribution ; Regression Analysis ; *Software ; }, abstract = {The kernel function plays a central role in kernel methods. Most existing methods can only adapt the kernel parameters or the kernel matrix based on empirical data. Recently, Ong et al. introduced the method of hyperkernels which can be used to learn the kernel function directly in an inductive setting. However, the associated optimization problem is a semidefinite program (SDP), which is very computationally expensive, even with the recent advances in interior point methods. In this paper, we show that this learning problem can be equivalently reformulated as a second-order cone program (SOCP), which can then be solved more efficiently than SDPs. Comparison is also made with the kernel matrix learning method proposed by Lanckriet et aL Experimental results on both classification and regression problems, with toy and real-world data sets, show that our proposed SOCP formulation has significant speedup over the original SDP formulation. Moreover, it yields better generalization than Lanckriet et al.'s method, with a speed that is comparable, or sometimes even faster, than their quadratically constrained quadratic program (QCQP) formulation.}, } @article {pmid16514490, year = {2005}, author = {Palmowski-Wolfe, AM and Woerdehoff, U}, title = {A comparison of the fast stimulation multifocal-ERG in patients with an IOL and control groups of different age.}, journal = {Documenta ophthalmologica. Advances in ophthalmology}, volume = {111}, number = {2}, pages = {87-93}, pmid = {16514490}, issn = {0012-4486}, mesh = {Adult ; Age Factors ; Aged ; Electroretinography/methods ; Humans ; *Lenses, Intraocular ; Middle Aged ; Photic Stimulation/methods ; Pseudophakia/*physiopathology ; Retina/*physiopathology ; }, abstract = {PURPOSE: It has been shown that a cataract significantly reduces mfERG responses in the central 4-14 degrees . Removing the cataract, leads to a significant increase in the response of the central 4 degrees . In this study we compare the mfERG of Woerdehoff et al.'s patients' [Doc Ophthalmol 2004; 108(1): 67-75] following cataract surgery to a healthy control group in order to assess whether, in the elderly, further influences of age need to be considered in addition to optical effects.

METHODS: Eighteen patients with an IOL following cataract surgery and 29 healthy volunteers (without clouding of the media or retinal changes) underwent testing of the mfERG (103 hexagons stimulating the central 50 degrees , M-sequence 2(15), Lmax: 200 cd/m2, Lmin<1 cd/m2). For the first order response component we compared the latencies of N1,P1 and N2 as well as the natural logarithm (ln) of the amplitudes N1P1 and P1N2 for four group averages: I. the central 4 degrees, II. 4-7 degrees, III. 7-10 degrees and IV. 10-15 degrees.

RESULTS: Mean age was 67 years (SD 10.1) for the IOL patients, 28.5 years (SD 5.6) for a young group of controls (n=15) and 60.2 years (SD 9.2) for the older control group (n=14). Patients with an IOL did not differ in latency from either control group (ANOVA, Tukey). Interestingly, at 10-15 degrees eccentricity, the latency of N2 differed significantly between the younger (41.4 ms, SD 1.4) and the older (43.0 ms, SD 1.9) control group. In the central 4 degrees LnN1P1 amplitudes were significantly lower in the IOL group (mean: 3.7, SD 0.2) than either the younger (mean: 3.9, SD 3.3) or the older (mean: 4.0, SD 0.3) control group. In all other amplitude measures, the older control group had slightly larger mean amplitudes than the younger control group and significantly larger amplitudes than the patients with an IOL, whose amplitudes were lowest.

DISCUSSION: Both, primarily optical but also neural phenomena have been described to affect the mfERG changes observed with age. Our results, are in support of this, as the improvement of the mfERG response following cataract surgery does not seem to reach the level of a healthy control group of equal age. Thus, our results suggest, that a control group with an IOL should be used when retinal function is tested in subjects with an IOL.}, } @article {pmid16510487, year = {2006}, author = {Hoshi, R and Pratt, H and Mehta, S and Bond, AJ and Curran, HV}, title = {An investigation into the sub-acute effects of ecstasy on aggressive interpretative bias and aggressive mood - are there gender differences?.}, journal = {Journal of psychopharmacology (Oxford, England)}, volume = {20}, number = {2}, pages = {291-301}, doi = {10.1177/0269881106060505}, pmid = {16510487}, issn = {0269-8811}, mesh = {Adult ; Affect/*drug effects ; Aggression/*drug effects ; Alcoholic Intoxication/psychology ; Amphetamine-Related Disorders/*psychology ; Anxiety/psychology ; Attention/*drug effects ; Concept Formation/drug effects ; Depression/psychology ; Drug Interactions ; Female ; Hallucinogens/*toxicity ; Humans ; Male ; Marijuana Abuse/psychology ; Memory, Short-Term/drug effects ; N-Methyl-3,4-methylenedioxyamphetamine/*toxicity ; Reaction Time/drug effects ; Reading ; Serotonin Agents/*toxicity ; Set, Psychology ; Sex Factors ; Substance Withdrawal Syndrome/*psychology ; }, abstract = {The lowering of serotonin for a period following MDMA use could account for the increases in both self-rated and objective measures of aggression previously found in ecstasy users several days after taking the drug. There is some evidence of gender differences in the acute, sub-acute and long-term effects of MDMA use, and given that gender differences have been found in aggression, it is possible that men may experience more aggression mid-week than women. The aim of this study was to attempt to replicate findings showing increased bias towards aggressive material in ecstasy users several days after using the drug. In addition, to investigate possible gender differences in mid-week aggression. A total of 46 participants were tested: 19 ecstasy users and 27 controls were compared on the night of drug use and 4 days later. On day 4, a task designed to tap cognitive bias toward material with aggressive content was administered. Participants were required to process sentences that could be interpreted as either aggressive or neutral and subsequently remember them in a recognition test. This data set was then combined with the data from Curran et al.'s (2004) study that employed exactly the same procedure. Thus, the data from 107 participants was analysed to investigate gender differences. Ecstasy users recognized more aggressive sentences than controls and tended to react slower to neutral sentences than controls. Ecstasy users also rated themselves as being more aggressive and depressed than controls on day 4. No gender differences were found on any measure of aggression in the combined data set. Both male and female ecstasy users show a bias toward interpretation of ambiguous material in an aggressive manner when compared to controls 4 days after ecstasy use.}, } @article {pmid16509107, year = {2006}, author = {Hiscock, M and Caroselli, JS and Wood, S}, title = {Concurrent counting and typing: lateralized interference depends on a difference between the hands in motor skill.}, journal = {Cortex; a journal devoted to the study of the nervous system and behavior}, volume = {42}, number = {1}, pages = {38-47}, doi = {10.1016/s0010-9452(08)70320-4}, pmid = {16509107}, issn = {0010-9452}, mesh = {Adolescent ; Adult ; Analysis of Variance ; Attention/*physiology ; Discrimination, Psychological ; Female ; *Field Dependence-Independence ; Fingers ; Functional Laterality/*physiology ; Humans ; Male ; Mathematics ; Motor Skills/*physiology ; Problem Solving/*physiology ; Reference Values ; }, abstract = {In previous demonstrations of differences between left- and right-handers in dual-task performance, participants' hand preference has been confounded with asymmetry of manual skill. The present study was designed to disentangle those two factors as sources of lateralized interference in the concurrent-task paradigm. Forty-eight normal adults (24 females and 24 males) counted backward by ones or by twos while typing an easy or difficult sequence of letters with either hand. When participants were grouped according to self-reported hand preference, both groups showed bilaterally symmetric slowing, relative to single-task conditions. However, when the same participants were grouped according to manual asymmetry in the baseline condition, the cognitive task interfered significantly more with the faster hand than with the slower hand. Baseline typing rate, averaged across hands, did not influence dual-task interference. Both self-reported left-hand preference and left-hand superiority in baseline typing were associated with reduced interference on the cognitive task, and the reduced interference in those groups seemed to reflect relatively loose coupling between manual and cognitive tasks. The results support and extend Caroselli et al.'s (1997) findings regarding the effect of baseline manual asymmetry on the pattern of dual-task interference. Irrespective of the participant's hand preference, the presence or absence of baseline asymmetry may be sufficient to determine whether dual-task interference is lateralized.}, } @article {pmid16505136, year = {2006}, author = {Rasgon, N and Jarvik, L}, title = {Cannon-Spoor et al.'s Assessment.}, journal = {The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry}, volume = {14}, number = {3}, pages = {293}, doi = {10.1097/01.JGP.0000192506.33563.f0}, pmid = {16505136}, issn = {1064-7481}, mesh = {Aged ; Alzheimer Disease/diagnosis/*epidemiology/psychology ; Cognition Disorders/diagnosis/*epidemiology/psychology ; Comorbidity ; Cross-Sectional Studies ; Depressive Disorder, Major/diagnosis/*epidemiology/psychology ; Humans ; Incidence ; Neuropsychological Tests ; Statistics as Topic ; }, } @article {pmid16496105, year = {2006}, author = {Schima, W and Ba-Ssalamah, A and Plank, C and Kulinna-Cosentini, C and Püspök, A}, title = {[Pancreas. Part I: congenital changes, acute and chronic pancreatitis].}, journal = {Der Radiologe}, volume = {46}, number = {4}, pages = {321-35; quiz 336}, pmid = {16496105}, issn = {0033-832X}, mesh = {Acute Disease ; Cholangiopancreatography, Magnetic Resonance/*methods ; Contrast Media ; Humans ; Image Enhancement/*methods ; Pancreatitis/*congenital/*diagnosis ; Pancreatitis, Chronic ; Practice Guidelines as Topic ; Subtraction Technique ; Tomography, X-Ray Computed/*methods ; }, abstract = {The pancreas develops from ventral and the dorsal buds, which undergo fusion. Failure to fuse results in pancreas divisum, which is defined by separate pancreatic ductal systems draining into the duodenum. Risk of developing pancreatitis is increased in pancreas divisum because of insufficient drainage. MR cholangiopancreatography (MRCP) is the technique of choice for detecting pancreas divisum non-invasively. Annular pancreas is the result of incomplete rotation of the pancreatic bud around the duodenum with the persistence of parenchyma or a fibrous band encircling (and sometimes stenosing) the duodenum. Acute pancreatitis is usually caused by bile duct stones or alcohol abuse. The Atlanta classification differentiates between mild acute and severe acute pancreatitis associated with organ failure and/or local complications such as necrosis, abscess or pseudocyst. Contrast-enhanced multi-detector row CT is the method of choice to assess the extent of disease. Balthazar et al.'s CT severity index assesses the risk of mortality and morbidity. In acute pancreatitis, the role of MRCP is mainly limited to finding bile duct stones in patients with suspected biliary pancreatitis. Chronic pancreatitis results in relentless and irreversible loss of exocrine (and sometimes endocrine) function of the pancreas. MDCT even shows subtle calcifications. MRCP is the method of choice for non-invasive assessment of the duct. Inflammatory pseudotumor in chronic pancreatitis and groove pancreatitis are difficult to differentiate from pancreatic cancer. In these cases, multiple imaging methods such as MDCT, MRI and endosonography including biopsy may be used to make a diagnosis.}, } @article {pmid16494965, year = {2006}, author = {Huang, G and Huang, Q and Zhan, H}, title = {Evidence of one-dimensional scale-dependent fractional advection-dispersion.}, journal = {Journal of contaminant hydrology}, volume = {85}, number = {1-2}, pages = {53-71}, doi = {10.1016/j.jconhyd.2005.12.007}, pmid = {16494965}, issn = {0169-7722}, mesh = {Computer Simulation ; Finite Element Analysis ; *Models, Chemical ; Sodium Chloride/chemistry ; *Soil ; *Water Movements ; Water Pollutants, Chemical ; }, abstract = {A semi-analytical inverse method and the corresponding program FADEMain for parameter estimation of the fractional advection-dispersion equation (FADE) were developed in this paper. We have analyzed Huang et al.'s [Huang, K., Toride, N., van Genuchten, M.Th., 1995. Experimental investigation of solute transport in large homogeneous and heterogeneous saturated soil columns. Trans. Porous Media 18, 283-302.] laboratory experimental data of conservative solute transport in 12.5-m long homogeneous and heterogeneous soil columns to test the non-Fickian dispersion theory of FADE. The dispersion coefficient was calculated by fitting the analytical solution of FADE to the measured data at different transport scales. We found that the dispersion coefficient increased exponentially with transport scale for the homogeneous column, whereas it increased with transport scale in a power law function for the heterogeneous column. The scale effect of the dispersion coefficient in the heterogeneous soil was much more significant comparing to that in the homogeneous soil. The increasing rate of dispersion coefficient versus transport distance was smaller for FADE than that for the advection-dispersion equation (ADE). Finite difference numerical approximations of the scale-dependent FADE were established to interpret the experimental results. The numerical solutions were found to be adequate for predicting scale-dependent transport in the homogeneous column, while the prediction for the heterogeneous column was less satisfactory.}, } @article {pmid16484099, year = {2006}, author = {Fuggetta, GP}, title = {Impairment of executive functions in boys with attention deficit/hyperactivity disorder.}, journal = {Child neuropsychology : a journal on normal and abnormal development in childhood and adolescence}, volume = {12}, number = {1}, pages = {1-21}, doi = {10.1080/09297040500203418}, pmid = {16484099}, issn = {0929-7049}, mesh = {Attention Deficit Disorder with Hyperactivity/*epidemiology ; Child ; Cognition Disorders/diagnosis/*epidemiology/physiopathology ; Diagnostic and Statistical Manual of Mental Disorders ; Frontal Lobe/physiopathology ; Humans ; Inhibition, Psychological ; Male ; Prevalence ; Reaction Time ; }, abstract = {The main aim of the present study is to compare the efficiency of executive control processes in 24 boys with attention deficit/hyperactivity disorder (ADHD) and 58 normal controls of similar age (between 8 and 11 years). Three reaction time (RT) paradigms were utilized: a dual task that requires coordination of two tasks responses, a shift task that makes it necessary to disengage attention from one task and engage into another one, and a stimulus-response spatial compatibility task that requires participants to inhibit a prepotent response. Another purpose of the study is to examine whether Barkley's (1997) executive dysfunction or Sergeant et al.'s (1999) resource allocation/arousal model best account for the behavioral deficits associated with ADHD. Examination of raw RT data showed significantly poorer performance in ADHD children with respect to age-matched controls on both the higher-level cognitive functions of executive control and on lower-level abilities (e.g., speed of processing) of all tasks of this study. However, using proportional transformations of raw RT data, we could demonstrate that, in addition to differences in processing speed, also executive control processes were significantly impaired in children with ADHD.}, } @article {pmid16473269, year = {2006}, author = {Farrell, RP}, title = {Rational versus anti-rational interpretations of science: an ape-language case-study.}, journal = {Studies in history and philosophy of biological and biomedical sciences}, volume = {37}, number = {1}, pages = {83-100}, doi = {10.1016/j.shpsc.2005.12.006}, pmid = {16473269}, issn = {1369-8486}, mesh = {*Animal Communication ; Animals ; Causality ; Child Development ; Child, Preschool ; *Hominidae ; Humans ; Imitative Behavior ; Infant ; *Language ; Linguistics ; Manual Communication ; Pan troglodytes ; }, abstract = {Robert Nola (2003) has argued that anti-rationalist interpretations of science fail to adequately explain the process of science, since objective reasons can be causal factors in belief formation. While I agree with Nola that objective reasons can be a cause of belief, in this paper I present a version of the strong programme in the sociology of knowledge, the Interests Thesis, and argue that the Interests Thesis provides a plausible explanation of an episode in the history of ape-language research. Specifically, I examine Terrace, Petitto, Sandess, & Bever (1979, 1980) illegitimate comparison of the signing of their chimpanzee, Nim, with data from human early childhood language development, and argue that Terrace et al.'s interests played a causal role in determining their sceptical beliefs concerning ape linguistic abilities. However, I go on to argue that Terrace et al.'s interests are not the only causal factors in determining their beliefs: objective reasons, associated with the institution of new methodologies, were also causally determinative of Terrace et al.'s sceptical beliefs. Consequently, I argue that belief formation in science is a multi-factorial affair wherein both interests and objective reasons have causal roles. I finish the paper with two conjectures concerning the proper locus of scientific rationality.}, } @article {pmid16465508, year = {2006}, author = {Freire, RO and Rocha, GB and Simas, AM}, title = {Lanthanide complex coordination polyhedron geometry prediction accuracies of ab initio effective core potential calculations.}, journal = {Journal of molecular modeling}, volume = {12}, number = {4}, pages = {373-389}, pmid = {16465508}, issn = {0948-5023}, mesh = {*Computer Simulation ; Crystallization ; Ions/chemistry ; Lanthanoid Series Elements/*chemistry ; Models, Molecular ; Molecular Conformation ; }, abstract = {lanthanide coordination compounds efficiently and accurately is central for the design of new ligands capable of forming stable and highly luminescent complexes. Accordingly, we present in this paper a report on the capability of various ab initio effective core potential calculations in reproducing the coordination polyhedron geometries of lanthanide complexes. Starting with all combinations of HF, B3LYP and MP2(Full) with STO-3G, 3-21G, 6-31G, 6-31G* and 6-31+G basis sets for [Eu(H2O)9]3+ and closing with more manageable calculations for the larger complexes, we computed the fully predicted ab initio geometries for a total of 80 calculations on 52 complexes of Sm(III), Eu(III), Gd(III), Tb(III), Dy(III), Ho(III), Er(III) and Tm(III), the largest containing 164 atoms. Our results indicate that RHF/STO-3G/ECP appears to be the most efficient model chemistry in terms of coordination polyhedron crystallographic geometry predictions from isolated lanthanide complex ion calculations. Moreover, both augmenting the basis set and/or including electron correlation generally enlarged the deviations and aggravated the quality of the predicted coordination polyhedron crystallographic geometry. Our results further indicate that Cosentino et al.'s suggestion of using RHF/3-21G/ECP geometries appears to be indeed a more robust, but not necessarily, more accurate recommendation to be adopted for the general lanthanide complex case. [Figure: see text].}, } @article {pmid16458852, year = {2006}, author = {McEvoy, PM and Kingsep, P}, title = {The post-event processing questionnaire in a clinical sample with social phobia.}, journal = {Behaviour research and therapy}, volume = {44}, number = {11}, pages = {1689-1697}, doi = {10.1016/j.brat.2005.12.005}, pmid = {16458852}, issn = {0005-7967}, mesh = {Adult ; Anxiety/psychology ; Female ; Humans ; *Interpersonal Relations ; Male ; *Mental Recall ; Phobic Disorders/*psychology ; Psychiatric Status Rating Scales ; Psychometrics ; Reproducibility of Results ; Self-Assessment ; *Surveys and Questionnaires ; }, abstract = {Post-event processing (PEP) involving rumination about perceived inadequacy in a past social situation has been proposed as an important maintaining factor in social phobia. The three aims of this study were to examine (a) the factor structure and internal reliability of a modified version of the Post-Event Processing Questionnaire [Rachman, S., Grüter-Andrew, J., & Shafran, R. (2000). Post-event processing in social anxiety. Behaviour Research and Therapy, 38, 611-617] in a clinical sample with social phobia (N=117), (b) the associations between PEP and symptoms of anxiety and depression, and (c) the relationship between perspective-taking ('field' and 'observer') and anxiety. Principal axis factor analysis yielded a highly reliable one-factor solution in our clinical sample, which generally replicated Rachman et al.'s findings with a sample of undergraduate students. PEP was most strongly and independently associated with state anxiety when depression, general anxiety and stress were controlled for. Contrary to expectations, PEP was not related to measures of social anxiety. The relationship between perspective-taking and anxiety was more complex than expected. Theoretical implications of these findings are discussed with reference to contemporary cognitive-behavioural models of social phobia.}, } @article {pmid16433659, year = {2006}, author = {Aluja, A and Del Barrio, V and García, LF}, title = {Comparison of several shortened versions of the EMBU: exploratory and confirmatory factor analyses.}, journal = {Scandinavian journal of psychology}, volume = {47}, number = {1}, pages = {23-31}, doi = {10.1111/j.1467-9450.2006.00489.x}, pmid = {16433659}, issn = {0036-5564}, mesh = {Adolescent ; Child ; Factor Analysis, Statistical ; Female ; Humans ; Male ; *Parent-Child Relations ; *Psychological Tests ; *Psychology, Adolescent ; Psychometrics ; Spain ; *Surveys and Questionnaires ; }, abstract = {The aim of the present study was to analyze the psychometric properties of different versions of the EMBU (Egna Minnen av Barndoms Uppfostran - My memories of upbringing) in a non-clinical sample of adolescents. The factor structure of the questionnaire was studied by means of more adequate exploratory and confirmatory factor procedures in order to ascertain which version achieves a better fit to data. The 64-item version of the EMBU was administered to a non-clinical sample of 832 adolescents. Exploratory and Confirmatory factor analyses were carried out for successive versions of 64, 37, 24 and 23 items. The theoretical four-factor structure of the 64-item version is not replicated in a factor analysis through principal axis extraction with direct oblimin rotation. The "Favoring Subject" factor was not found. 37 items present loadings equal to or larger than 0.30 for the "Rejection", "Emotional Warmth" and "Overprotection" factors. A re-analysis of these items shows a clear three-factor structure. When Arrindell et al.'s (1999) 23-item version was analysed, the three expected factors were also found. Confirmatory factor analyses allow us to reduce the 36-item version to a shorter one of 24 items. This last version achieves the best fit to data, including the 23-item version. The new 24-item version improves the construct validity of the EMBU and presents similar reliability coefficients.}, } @article {pmid16433533, year = {2006}, author = {Nielsen, MF and Ingold, KU}, title = {Kinetic solvent effects on proton and hydrogen atom transfers from phenols. Similarities and differences.}, journal = {Journal of the American Chemical Society}, volume = {128}, number = {4}, pages = {1172-1182}, doi = {10.1021/ja0548081}, pmid = {16433533}, issn = {0002-7863}, abstract = {Bimolecular rate constants for proton transfer from six phenols to the anthracene radical anion have been determined in up to eight solvents using electrochemical techniques. Effects of hydrogen bonding on measured rate constants were explored over as wide a range of phenolic hydrogen-bond donor (HBD) and solvent hydrogen-bond acceptor (HBA) activities as practical. The phenols' values ranged from 0.261 (2-MeO-phenol) to 0.728 (3,5-Cl(2)-phenol), and the solvents' values from 0.44 (MeCN) to 1.00 (HMPA), where and are Abraham's parameters describing relative HBD and HBA activities (J. Chem. Soc., Perkin Trans. 2 1989, 699; 1990, 521). Rate constants for H-atom transfer (HAT) in HBA solvents, k(S), are extremely well correlated via log k(S) = log k(0) - 8.3 , where k(0) is the rate constant in a non-HBA solvent (Snelgrove et al. J. Am. Chem. Soc. 2001, 123, 469). The same equation describes the general features of proton transfers (k(S) decreases as increases, slopes of plots of log k(S) against increase as increases). However, in some solvents, k(S) values deviate systematically from the least-squares log k(S) versus correlation line (e.g., in THF and MeCN, k(S) is always smaller and larger, respectively, than "expected"). These deviations are attributed to variations in the solvents' anion solvating abilities (THF and MeCN are poor and good anion solvators, respectively). Values of log k(S) for proton transfer, but not for HAT, give better correlations with Taft et al.'s (J. Org. Chem. 1983, 48, 2877) beta scale of solvent HBA activities than with . The beta scale, therefore, does not solely reflect solvents' HBA activities but also contains contributions from anion solvation.}, } @article {pmid16419796, year = {2005}, author = {Voinovich, P and Merlen, A}, title = {Two-dimensional numerical simulation of acoustic wave phase conjugation in magnetostrictive elastic media.}, journal = {The Journal of the Acoustical Society of America}, volume = {118}, number = {6}, pages = {3491-3498}, doi = {10.1121/1.2130964}, pmid = {16419796}, issn = {0001-4966}, mesh = {*Acoustics ; *Computer Simulation ; Elasticity ; Electromagnetic Fields ; Image Processing, Computer-Assisted ; *Models, Theoretical ; Ultrasonics ; *Ultrasonography ; }, abstract = {The effect of parametric wave phase conjugation (WPC) in application to ultrasound or acoustic waves in magnetostrictive solids has been addressed numerically by Ben Khelil et al. [J. Acoust. Soc. Am. 109, 75-83 (2001)] using 1-D unsteady formulation. Here the numerical method presented by Voinovich et al. [Shock waves 13(3), 221-230 (2003)] extends the analysis to the 2-D effects. The employed model describes universally elastic solids and liquids. A source term similar to Ben Khelil et al.'s accounts for the coupling between deformation and magnetostriction due to external periodic magnetic field. The compatibility between the isotropic constitutive law of the medium and the model of magnetostriction has been considered. Supplementary to the 1-D simulations, the present model involves longitudinal/transversal mode conversion at the sample boundaries and separate magnetic field coupling with dilatation and shear stress. The influence of those factors in a 2-D geometry on the potential output of a magneto-elastic wave phase conjugator is analyzed in this paper. The process under study includes propagation of a wave burst of a given frequency from a point source in a liquid into the active solid, amplification of the waves due to parametric resonance, and formation of time-reversed waves, their radiation into liquid, and focusing. The considered subject is particularly important for ultrasonic applications in acoustic imaging, nondestructive testing, or medical diagnostics and therapy.}, } @article {pmid16408227, year = {2006}, author = {Naunton, M and Duyvendak, M and Peterson, GM and Brouwers, JR}, title = {Comments on Glintborg et al.'s drug-drug interactions study (EJCP 2005; 61: 675-681).}, journal = {European journal of clinical pharmacology}, volume = {62}, number = {2}, pages = {159-160}, pmid = {16408227}, issn = {0031-6970}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; *Drug Interactions ; *Drug-Related Side Effects and Adverse Reactions ; *Hospitalization ; Humans ; Middle Aged ; }, } @article {pmid16406105, year = {2006}, author = {Perkins, AM and Corr, PJ}, title = {Reactions to threat and personality: psychometric differentiation of intensity and direction dimensions of human defensive behaviour.}, journal = {Behavioural brain research}, volume = {169}, number = {1}, pages = {21-28}, doi = {10.1016/j.bbr.2005.11.027}, pmid = {16406105}, issn = {0166-4328}, mesh = {Adolescent ; Adult ; Aged ; Aggression/*psychology ; Anxiety/*psychology ; Defense Mechanisms ; Fear/*psychology ; Female ; Humans ; Male ; Middle Aged ; Orientation ; *Personality ; Personality Inventory ; Psychometrics ; Reference Values ; Sex Factors ; }, abstract = {Gray and McNaughton [Gray JA, McNaughton N. The neuropsychology of anxiety. Oxford: Oxford University Press; 2000] predict that fear is associated with orientation away from threat whereas anxiety is associated with orientation towards threat; this first dimension of 'defensive direction' is independent of a second dimension of 'defensive intensity'. Defensive reactions were measured using a threat scenario questionnaire developed by Blanchard et al. [Blanchard DC, Hynd AL, Minke KA, Minemoto T, Blanchard RJ. Human defensive behaviours to threat scenarios show parallels to fear- and anxiety-related defence patterns of non-human mammals. Neurosci Biobehav Rev 2001;25:761-70] who found that responses paralleled the defensive reactions of rodents faced with real threats. In a sample of 141 participants we replicated Blanchard et al.'s findings as well as confirming the Gray and McNaughton hypotheses. As predicted, trait anxiety was associated with a tendency to orientate towards threat. In addition, the personality trait of psychoticism (tough-mindedness) was related to defensive intensity with low scorers on psychoticism being more sensitive to threat in general and high scorers being more threat insensitive. A well-established personality measure of general punishment sensitivity, namely the Carver and White [Carver CS, White TL. Behavioural inhibition, behavioural activation, and affective responses to impending reward and punishment: the BIS/BAS scales. J Pers Soc Psychol 1994;67:319-33] BIS scale, was positively correlated with both defensive intensity and direction. These data indicate that the threat scenario questionnaire has some validity as a measure of human reactions to threat.}, } @article {pmid16401286, year = {2005}, author = {Albert, PS and Hunsberger, S}, title = {On analyzing circadian rhythms data using nonlinear mixed models with harmonic terms.}, journal = {Biometrics}, volume = {61}, number = {4}, pages = {1115-20; discussion 1120-2}, doi = {10.1111/j.0006-341X.2005.464_1.x}, pmid = {16401286}, issn = {0006-341X}, mesh = {Circadian Rhythm/*physiology ; Computer Simulation ; *Data Interpretation, Statistical ; Depression/metabolism ; Humans ; Hydrocortisone/metabolism ; *Nonlinear Dynamics ; Seasons ; }, abstract = {Wang, Ke, and Brown (2003, Biometrics59, 804-812) developed a smoothing-based approach for modeling circadian rhythms with random effects. Their approach is flexible in that fixed and random covariates can affect both the amplitude and phase shift of a nonparametrically smoothed periodic function. In motivating their approach, Wang et al. stated that a simple sinusoidal function is too restrictive. In addition, they stated that "although adding harmonics can improve the fit, it is difficult to decide how many harmonics to include in the model, and the results are difficult to interpret." We disagree with the notion that harmonic models cannot be a useful tool in modeling longitudinal circadian rhythm data. In this note, we show how nonlinear mixed models with harmonic terms allow for a simple and flexible alternative to Wang et al.'s approach. We show how to choose the number of harmonics using penalized likelihood to flexibly model circadian rhythms and to estimate the effect of covariates on the rhythms. We fit harmonic models to the cortisol circadian rhythm data presented by Wang et al. to illustrate our approach. Furthermore, we evaluate the properties of our procedure with a small simulation study. The proposed parametric approach provides an alternative to Wang et al.'s semiparametric approach and has the added advantage of being easy to implement in most statistical software packages.}, } @article {pmid16396187, year = {2005}, author = {Baldwin, BG}, title = {Origin of the serpentine-endemic herb Layia discoidea from the widespread L. glandulosa (Compositae).}, journal = {Evolution; international journal of organic evolution}, volume = {59}, number = {11}, pages = {2473-2479}, pmid = {16396187}, issn = {0014-3820}, mesh = {Asbestos, Serpentine ; Asteraceae/*genetics ; California ; DNA, Plant ; DNA, Ribosomal ; Environment ; Evolution, Molecular ; *Phylogeny ; Sequence Analysis, DNA ; }, abstract = {Phylogenetic analyses of nuclear rDNA sequences uphold Gottlieb et al.'s hypothesis that Layia discoidea, a morphologically unusual, serpentine-endemic herb of narrow distribution in central California, "budded off" recently (less than one million years ago) from a nearby lineage of the widespread L. glandulosa, which occurs on sandy soils across much of far western North America. Although L. discoidea and L. glandulosa retain complete interfertility, nuclear rDNA data for the two species are almost free of evolutionary noise, without evidence of gene flow between them; allopatric divergence of L. discoidea cannot be ruled out. Molecular data are consistent with a hypothesis of accelerated morphological evolution of L. discoidea and Gottlieb et al.'s suggestion that the closest relatives of L. discoidea are populations of L. glandulosa with yellow, rather than white, ray corollas, in accord with Clausen, Keck, and Hiesey's evidence of a gene for yellow ray coloration in the rayless L. discoidea.}, } @article {pmid16396017, year = {2005}, author = {Holt, LL and Stephens, JD and Lotto, AJ}, title = {A critical evaluation of visually moderated phonetic context effects.}, journal = {Perception & psychophysics}, volume = {67}, number = {6}, pages = {1102-1112}, doi = {10.3758/bf03193635}, pmid = {16396017}, issn = {0031-5117}, support = {R01 DC04674-01/DC/NIDCD NIH HHS/United States ; }, mesh = {Cues ; Humans ; *Phonetics ; *Speech Perception ; *Visual Perception ; }, abstract = {Fowler, Brown, and Mann (2000) have reported a visually moderated phonetic context effect in which a video disambiguates an acoustically ambiguous precursor syllable, which, in turn, influences perception of a subsequent syllable. In the present experiments, we explored this finding and the claims that stem from it. Experiment 1 failed to replicate Fowler et al. with novel materials modeled after the original study, but Experiment 2 successfully replicated the effect, using Fowler et al.'s stimulus materials. This discrepancy was investigated in Experiments 3 and 4, which demonstrate that variation in visual information concurrent with the test syllable is sufficient to account for the original results. Fowler et al.'s visually moderated phonetic context effect appears to have been a demonstration of audiovisual interaction between concurrent stimuli, and not an effect whereby preceding visual information elicits changes in the perception of subsequent speech sounds.}, } @article {pmid16383372, year = {2005}, author = {Pendleton, DE and Dathe, A and Baveye, P}, title = {Influence of image resolution and evaluation algorithm on estimates of the lacunarity of porous media.}, journal = {Physical review. E, Statistical, nonlinear, and soft matter physics}, volume = {72}, number = {4 Pt 1}, pages = {041306}, doi = {10.1103/PhysRevE.72.041306}, pmid = {16383372}, issn = {1539-3755}, abstract = {In recent years, experience has demonstrated that the classical fractal dimensions are not sufficient to describe uniquely the interstitial geometry of porous media. At least one additional index or dimension is necessary. Lacunarity, a measure of the degree to which a data set is translationally invariant, is a possible candidate. Unfortunately, several approaches exist to evaluate it on the basis of binary images of the object under study, and it is unclear to what extent the lacunarity estimates that these methods produce are dependent on the resolution of the images used. In the present work, the gliding-box algorithm of Allain and Cloitre [Phys. Rev. A 44, 3552 (1991)] and two variants of the sandbox algorithm of Chappard et al. [J. Pathol. 195, 515 (2001)], along with three additional algorithms, are used to evaluate the lacunarity of images of a textbook fractal, the Sierpinski carpet, of scanning electron micrographs of a thin section of a European soil, and of light transmission photographs of a Togolese soil. The results suggest that lacunarity estimates, as well as the ranking of the three tested systems according to their lacunarity, are affected strongly by the algorithm used, by the resolution of the images to which these algorithms are applied, and, at least for three of the algorithms (producing scale-dependent lacunarity estimates), by the scale at which the images are observed. Depending on the conditions under which the estimation of the lacunarity is carried out, lacunarity values range from 1.02 to 2.14 for the three systems tested, and all three of the systems used can be viewed alternatively as the most or the least "lacunar." Some of this indeterminacy and dependence on image resolution is alleviated in the averaged lacunarity estimates yielded by Chappard et al.'s algorithm. Further research will be needed to determine if these lacunarity estimates allow an improved, unique characterization of porous media.}, } @article {pmid16382088, year = {2006}, author = {Miller, AB and Cross, T}, title = {Ethnicity in child maltreatment research: a replication of Behl et al.'s content analysis.}, journal = {Child maltreatment}, volume = {11}, number = {1}, pages = {16-26}, doi = {10.1177/1077559505278272}, pmid = {16382088}, issn = {1077-5595}, mesh = {Child ; Child Abuse/*ethnology/*statistics & numerical data ; Ethnicity/*statistics & numerical data ; Humans ; }, abstract = {This study examines the use of ethnicity in 489 empirical research articles published in three major child maltreatment specialty journals from 1999 to 2002. Of the American samples, 12.5% focus on ethnicity, 76.2% report the ethnic composition of participants, and 33.8% use ethnicity of participants in analyses. Ethnicity has a significant effect in 52.3% of articles in which it was used in analyses, suggesting its importance as a variable in a wide range of studies. African Americans and Native Americans are underrepresented in research samples. These findings indicate more attention to ethnicity in American research than Behl, Crouch, May, Valente, and Conyngham's 2001 study might suggest but also highlight the need for continued expansion in focusing on, reporting, and using ethnicity in research.}, } @article {pmid16355750, year = {2005}, author = {Shu, H and Meng, X and Chen, X and Luan, H and Cao, F}, title = {The subtypes of developmental dyslexia in Chinese: evidence from three cases.}, journal = {Dyslexia (Chichester, England)}, volume = {11}, number = {4}, pages = {311-329}, doi = {10.1002/dys.310}, pmid = {16355750}, issn = {1076-9242}, mesh = {Adolescent ; *Asian People ; Child ; Dyslexia/*classification/*diagnosis ; Humans ; Male ; Severity of Illness Index ; Verbal Behavior ; }, abstract = {This study investigated subtypes of developmental dyslexia in Chinese by assessing three cases of Chinese dyslexic children. A battery of screening measures, a character naming and meaning task, and metalinguistic awareness tasks were administered to each child. One of the three children demonstrated characteristics of developmental surface dyslexia, and the other two showed characteristics of developmental deep dyslexia. Moreover, the children's reading problems were found to be specifically related to their deficits in metalinguistic awareness. The dissociation between developmental surface and deep dyslexia provides support to Weekes et al.'s (Neurocase 1997; 3: 51-60) model that a semantic and a nonsemantic pathway exist independently in Chinese reading. The results also suggest that deficits in morphological and phonological awareness may cause developmental delays in the semantic and the nonsemantic pathway.}, } @article {pmid16351687, year = {2005}, author = {Byskov, AG and Faddy, MJ and Lemmen, JG and Andersen, CY}, title = {Eggs forever?.}, journal = {Differentiation; research in biological diversity}, volume = {73}, number = {9-10}, pages = {438-446}, doi = {10.1111/j.1432-0436.2005.00045.x}, pmid = {16351687}, issn = {0301-4681}, mesh = {Animals ; Cell Differentiation ; Female ; Follicular Atresia/physiology ; Humans ; Meiosis ; Mice ; Mice, Inbred C57BL ; Oocytes/*cytology ; Ovary/anatomy & histology ; Ovum/*cytology ; }, abstract = {A group of scientists from Harvard Medical School (Johnson et al., 2004) claims to have "established the existence of proliferative germ cells that sustain oocyte and follicle production in the postnatal mammalian ovary," expressing no doubts about their methods, results and conclusion. Johnson et al. based their conclusions of oocyte and follicular renewal from existing germline stem cells (GSC) in the postnatal mouse ovary on three types of observations: (1) A claimed discordance in follicle loss versus follicle atresia in the neonatal period and in the following pubertal and adult period; (2) immunohistochemical detection of proliferating GSC with meiotic capacity using combined markers for meiosis, germline, and mitosis; and (3) neo-folliculogenesis in ovarian chimeric grafting experiments with adult mice. Oogenesis is the process that transforms the proliferative oogonium into an oocyte through meiosis, followed by folliculogenesis and follicular and oocyte maturation. The most crucial part in producing a functional oocyte is firstly, initiation and completion of the first meiotic prophase, and secondly, enclosure of the resulting diplotene oocyte in a follicle. Neither of these two events has been shown to take place in Johnson et al.'s study of the postnatal mouse ovary. We hereby address the observations underpinning their hypothesis and conclude that it is premature to replace the paradigm that adult mammalian neo-oogenesis/folliculogenesis does not take place.}, } @article {pmid16351342, year = {2005}, author = {Greenberg, G}, title = {The limitations of behavior-genetic analyses: comment on McGue, Elkins, Walden, and Iacono (2005).}, journal = {Developmental psychology}, volume = {41}, number = {6}, pages = {989-92; discussion 993-7}, doi = {10.1037/0012-1649.41.6.989}, pmid = {16351342}, issn = {0012-1649}, mesh = {Adolescent ; Child ; *Child Development ; Cohort Studies ; *Conflict, Psychological ; Female ; *Genetics, Behavioral ; Humans ; Longitudinal Studies ; Male ; Models, Genetic ; *Parent-Child Relations ; Sex Factors ; Social Environment ; Statistics as Topic ; Surveys and Questionnaires ; Twins/*genetics/*psychology ; }, abstract = {This article takes issue with the behavior-genetic analysis of parenting style presented by M. McGue, I. Elkins, B. Walden, and W. G. Iacono. The author argues that the attribution of their findings to inherited genetic effects was without basis because McGue et al. never indicated how those genetic effects manifested themselves. Instead, McGue et al. neglected important, and inevitable, developmental effects that most developmental psychologists understand to influence parent and adolescent behavior. The author also suggests that there is great merit in adopting the approach of developmental systems theory in understanding McGue et al.'s findings in particular and all developmental phenomena in general.}, } @article {pmid16342579, year = {2005}, author = {Takezawa, T and Miyatani, M}, title = {Quantitative relation between conflict and response inhibition in the Flanker task.}, journal = {Psychological reports}, volume = {97}, number = {2}, pages = {515-526}, doi = {10.2466/pr0.97.2.515-526}, pmid = {16342579}, issn = {0033-2941}, mesh = {Adult ; *Cognition ; Female ; Fixation, Ocular ; Humans ; *Inhibition, Psychological ; Male ; *Psychological Tests ; *Reaction Time ; *Signal Detection, Psychological ; Social Behavior ; }, abstract = {The 2001 conflict monitoring hypothesis of Botvinick and colleagues posits that the amount of conflict raised by incongruent stimuli in a flanker task affects subsequent cognitive control, such as response inhibition. The present experiment yielded empirical evidence of the quantitative relation between conflict and response inhibition. Participants judged the direction of a target arrow flanked by distractor arrows presented above and below the target. The amount of conflict was manipulated by varying the distance between the target and the directional distractors. Analysis showed that response times were longer for incongruent trials than for congruent trials, and response times on incongruent trials were longer for the small distance than for the large distance conditions. In addition, the response times in congruent trials became longer as the amount of conflict in the preceding trial increased. These results are consistent with Botvinick, et al.'s hypothesis that the conflict-detection mechanism determines the amount of response inhibition depending on the amount of conflict. Responses on incongruent trials were faster and more accurate when the preceding trial was incongruent than when it was congruent, and the size of this response facilitation was not influenced by the amount of conflict. These results suggest that the conflict detection mechanism modulates the subsequent behaviors by two forms of control which are differently affected by the amount of conflict.}, } @article {pmid16332009, year = {2005}, author = {Prasad, SS}, title = {Especially significant new component of N2O quantum yield in the UV photolysis of O3 in air.}, journal = {The journal of physical chemistry. A}, volume = {109}, number = {40}, pages = {9035-9043}, doi = {10.1021/jp058114q}, pmid = {16332009}, issn = {1089-5639}, abstract = {This paper presents an alternate three-component model for the density ([M]) and temperature (T) dependence of the N2O quantum yields (phi(N2O), in the UV photolysis of O3 in air, from Estupiñán et al.'s (ENLCW's) high-quality experiments that were a breakthrough in the pressure and T coverage. The three components consist of a new [M]-independent component, the ENLCW-discovered [M]1 component, and the [M]2-dependent component found by Kajimoto and Cvetanovic. The [M]1 component is T independent. The weak T dependence of ENLCW's phi(N2O) results from the T dependence of the other two components. The agreement of the three-component model with the observed phi(N2O) is much better than that of ENLCW's one-component (T-dependent linear-in-[M]) model. For example, the percentage residual for a significant two-thirds of all data is better than +/-8% in the three-component model compared to only one-third for the ENLCW model. The improvements due to the three-component model are real in the sense that they are obvious despite the experimental error bars in that pressure-temperature domain where the reality is expected to reveal itself in the ENLCW experiment. Also, the new [M]-independent component is nonzero positive at a very high confidence level of 97.5%, sharply contrasting with the current perception. The [M]-independent component is especially significant despite being small compared to the dominant [M]1 component. It implies N2O formation from excited O3, tentatively O3(3B1), immune from ENLCW and Prasad controversy over the origin of the [M]1 component. In the suggested interpretation, the [M]0 component varies linearly with [O3] in the photolyzed O3/air mixture. Further experiments with [O3] fixed at various amounts, while the air density and temperature are varied, could check the interpretation. Further computational-chemistry studies to better characterize the low-lying triplet states of O3 would also help.}, } @article {pmid16320267, year = {2005}, author = {Le Teuff, G and Abrahamowicz, M and Bolard, P and Quantin, C}, title = {Comparison of Cox's and relative survival models when estimating the effects of prognostic factors on disease-specific mortality: a simulation study under proportional excess hazards.}, journal = {Statistics in medicine}, volume = {24}, number = {24}, pages = {3887-3909}, doi = {10.1002/sim.2392}, pmid = {16320267}, issn = {0277-6715}, mesh = {Aged ; Colorectal Neoplasms/mortality ; Female ; France ; Humans ; Male ; Middle Aged ; Prognosis ; *Proportional Hazards Models ; *Survival Analysis ; }, abstract = {In many prognostic studies focusing on mortality of persons affected by a particular disease, the cause of death of individual patients is not recorded. In such situations, the conventional survival analytical methods, such as the Cox's proportional hazards regression model, do not allow to discriminate the effects of prognostic factors on disease-specific mortality from their effects on all-causes mortality. In the last decade, the relative survival approach has been proposed to deal with the analyses involving population-based cancer registries, where the problem of missing information on the cause of death is very common. However, some questions regarding the ability of the relative survival methods to accurately discriminate between the two sources of mortality remain open. In order to systematically assess the performance of the relative survival model proposed by Esteve et al., and to quantify its potential advantages over the Cox's model analyses, we carried out a series of simulation experiments, based on the population-based colon cancer registry in the French region of Burgundy. Simulations showed a systematic bias induced by the 'crude' conventional Cox's model analyses when individual causes of death are unknown. In simulations where only about 10 per cent of patients died of causes other than colon cancer, the Cox's model over-estimated the effects of male gender and oldest age category by about 17 and 13 per cent, respectively, with the coverage rate of the 95 per cent CI for the latter estimate as low as 65 per cent. In contrast, the effect of higher cancer stages was under-estimated by 8-28 per cent. In contrast to crude survival, relative survival model largely reduced such problems and handled well even such challenging tasks as separating the opposite effects of the same variable on cancer-related versus other-causes mortality. Specifically, in all the cases discussed above, the relative bias in the estimates from the Esteve et al.'s model was always below 10 per cent, with the coverage rates above 81 per cent.}, } @article {pmid16316293, year = {2005}, author = {Dalgleish, T}, title = {Putting some feeling into it--the conceptual and empirical relationships between the classic and emotional Stroop tasks: comment on Algom, Chajut, and Lev (2004).}, journal = {Journal of experimental psychology. General}, volume = {134}, number = {4}, pages = {585-91; discussion 592-5}, doi = {10.1037/0096-3445.134.4.585}, pmid = {16316293}, issn = {0096-3445}, mesh = {*Affect ; *Attention ; Humans ; *Psychological Tests ; }, abstract = {D. Algom, E. Chajut, and S. Lev presented a series of definitional, conceptual, and empirical arguments in support of their conclusion that the classic and emotional Stroop effects are, in their words, "unrelated phenomena" (p. 336), such that the term emotional Stroop effect is a misnomer in reference to the relatively greater interference in ink color naming of emotional versus neutral words. These are strong claims. In this comment, the author critically examines each component of Algom et al.'s case and argues that, in fact, none of these components represents compelling evidence in support of their eventual conclusions.}, } @article {pmid16315108, year = {2005}, author = {Mitchell, A and Graur, D}, title = {Inferring the pattern of spontaneous mutation from the pattern of substitution in unitary pseudogenes of Mycobacterium leprae and a comparison of mutation patterns among distantly related organisms.}, journal = {Journal of molecular evolution}, volume = {61}, number = {6}, pages = {795-803}, pmid = {16315108}, issn = {0022-2844}, mesh = {Animals ; DNA, Mitochondrial/genetics ; *Evolution, Molecular ; Humans ; *Mutation ; Mycobacterium leprae/*genetics ; *Phylogeny ; *Pseudogenes ; }, abstract = {The pattern of spontaneous mutation can be inferred from the pattern of substitution in pseudogenes, which are known to be under very weak or no selective constraint. We modified an existing method (Gojobori T, et al., J Mol Evol 18:360, 1982) to infer the pattern of mutation in bacteria by using 569 pseudogenes from Mycobacterium leprae. In Gojobori et al.'s method, the pattern is inferred by using comparisons involving a pseudogene, a conspecific functional paralog, and an outgroup functional ortholog. Because pseudogenes in M. leprae are unitary, we replaced the missing paralogs by functional orthologs from M. tuberculosis. Functional orthologs from Streptomyces coelicolor served as outgroups. We compiled a database consisting of 69,378 inferred mutations. Transitional mutations were found to constitute more than 56% of all mutations. The transitional bias was mainly due to C-->T and G-->A, which were also the most frequent mutations on the leading strand and the only ones that were significantly more frequent than the random expectation. The least frequent mutations on the leading strand were A-->T and T-->A, each with a relative frequency of less than 3%. The mutation pattern was found to differ between the leading and the lagging strands. This asymmetry is thought to be the cause for the typical chirochoric structure of bacterial genomes. The physical distance of the pseudogene from the origin of replication (ori) was found to have almost no effect on the pattern of mutation. A surprising similarity was found between the mutation pattern in M. leprae and previously inferred patterns for such distant taxa as human and Drosophila. The mutation pattern on the leading strand of M. leprae was also found to share some common features with the pattern inferred for the heavy strand of the human mitochondrial genome. These findings indicate that taxon-specific factors may only play secondary roles in determining patterns of mutation.}, } @article {pmid16303290, year = {2005}, author = {Lamm, C and Fischmeister, FP and Bauer, H}, title = {Individual differences in brain activity during visuo-spatial processing assessed by slow cortical potentials and LORETA.}, journal = {Brain research. Cognitive brain research}, volume = {25}, number = {3}, pages = {900-912}, doi = {10.1016/j.cogbrainres.2005.09.025}, pmid = {16303290}, issn = {0926-6410}, mesh = {Artifacts ; Brain/*physiology ; Data Interpretation, Statistical ; Electroencephalography/statistics & numerical data ; Evoked Potentials/physiology ; Functional Laterality/physiology ; Humans ; Individuality ; Magnetic Resonance Imaging ; Space Perception/*physiology ; Visual Perception/*physiology ; }, abstract = {Using slow-cortical potentials (SCPs), Vitouch et al. demonstrated that subjects with low ability to solve a complex visuo-spatial imagery task show higher activity in occipital, parietal and frontal cortex during task processing than subjects with high ability. This finding has been interpreted in the sense of the so-called "neural efficiency" hypothesis, which assumes that the central nervous system of individuals with higher intellectual abilities is functioning in a more efficient way than the one of individuals with lower abilities. Using a higher spatial resolution of SCP recordings, and by employing the source localization method of LORETA (low-resolution electromagnetic tomography), we investigated this hypothesis by performing an extended replication of Vitouch et al.'s study. SCPs during processing of a visuo-spatial imagery task were recorded in pre-selected subjects with either high or low abilities in solving the imagery task. Topographic and LORETA analyses of SCPs revealed that a distributed network of extrastriate occipital, superior parietal, temporal, medial frontal and prefrontal areas was active during task solving. This network is well in line with former studies of the functional neuroanatomy of visuo-spatial imagery. Contrary to our expectations, however, the results of Vitouch et al. as well as of other studies supporting the neural efficiency hypothesis could not be confirmed since no difference in brain activity between groups was observed. This inconsistency between studies might be due to differing task processing strategies. While subjects with high abilities in the Vitouch et al. study seemed to use a visuo-perceptual task solving approach, all other subjects relied upon a visuo-motor task processing strategy.}, } @article {pmid16279315, year = {2005}, author = {Abdel-Khalek, A and Lester, D}, title = {Factorial structure of short scales measuring manic-depression in Kuwaiti undergraduates.}, journal = {Psychological reports}, volume = {97}, number = {1}, pages = {128}, doi = {10.2466/pr0.97.1.128-128}, pmid = {16279315}, issn = {0033-2941}, mesh = {Adult ; Bipolar Disorder/*diagnosis/ethnology/psychology ; *Cross-Cultural Comparison ; Ethnicity/*psychology ; Factor Analysis, Statistical ; Female ; Humans ; Kuwait ; Male ; Personality Inventory/*statistics & numerical data ; Psychometrics/statistics & numerical data ; Reproducibility of Results ; Students/*psychology ; }, abstract = {A sample of 202 Kuwaiti college students (63 men and 139 women; Mage=21.6 yr., SD=2.4) responded to the Thalbourne, et al.'s Manic-Depressiveness Scale. In a factor analysis with a varimax rotation, 14 of 18 items had significant loadings (>.3) on the first factor, including 8 items of the original depression scale. 6 items significantly loaded on the second factor, including 3 items of the original mania scale. This did not match the hypothetical structure of the scale.}, } @article {pmid16279311, year = {2005}, author = {Jenkins, I}, title = {Response to Skinner, et al. on "National personality characteristics: II. Adaption-innovation in Canadian, American, and British samples".}, journal = {Psychological reports}, volume = {97}, number = {1}, pages = {107-108}, doi = {10.2466/pr0.97.1.107-108}, pmid = {16279311}, issn = {0033-2941}, mesh = {Adult ; Bias ; Canada ; *Character ; *Cross-Cultural Comparison ; Female ; Humans ; Male ; *Personality ; Personality Inventory/statistics & numerical data ; Psychometrics/statistics & numerical data ; *Social Identification ; United Kingdom ; United States ; }, abstract = {Skinner, et al. interpreted as significant the difference between means for Canadian men and women on Kirton's inventory and those for British and American samples. The means were similar to prior values. Skinner, et al.'s groups were large and composed of very unequal numbers of men and women, which factors could account for their interpretation. As reported, their analysis is insufficient to interpret very small mean variations as differences in national character.}, } @article {pmid16279299, year = {2005}, author = {Tomás-Sábado, J and Gómez-Benito, J}, title = {Death anxiety and death depression in Spanish nurses.}, journal = {Psychological reports}, volume = {97}, number = {1}, pages = {21-24}, doi = {10.2466/pr0.97.1.21-24}, pmid = {16279299}, issn = {0033-2941}, mesh = {Adult ; Anxiety/*diagnosis ; *Attitude of Health Personnel ; *Attitude to Death ; Cross-Cultural Comparison ; Depression/*diagnosis ; Female ; Humans ; Male ; Middle Aged ; Nurses/*psychology ; Occupational Diseases/*diagnosis ; Personality Inventory/statistics & numerical data ; Psychometrics/statistics & numerical data ; Reproducibility of Results ; Spain ; }, abstract = {This study examined the dimensional structure of Tomás-Sábado and Gómez-Benito's Death Anxiety Inventory and Templer, et al.'s Death Depression Scale-Revised. The responses of 244 Spanish nurses to the Spanish forms of both scales were evaluated by means of a principal axis factor analysis with direct Oblimin rotation. Five significant factors were identified: Internally Generated Death Anxiety, Death Depression, Externally Generated Death Anxiety, Death Threat, and Death Sadness, accounting for 51.6% of the variance. The distribution of the factor loadings for the items of both scales on the five factors supported the discriminant validity of the constructs specific to each of the scales and justified their use in evaluating death anxiety and death depression independently.}, } @article {pmid16274661, year = {2006}, author = {Olatunji, BO and Sawchuk, CN and de Jong, PJ and Lohr, JM}, title = {The structural relation between disgust sensitivity and blood-injection-injury fears: a cross-cultural comparison of US and Dutch data.}, journal = {Journal of behavior therapy and experimental psychiatry}, volume = {37}, number = {1}, pages = {16-29}, doi = {10.1016/j.jbtep.2005.09.002}, pmid = {16274661}, issn = {0005-7916}, support = {1F31MH067519-1A1/MH/NIMH NIH HHS/United States ; }, mesh = {Adult ; *Affect ; *Blood ; Cross-Cultural Comparison ; *Fear ; Female ; Humans ; *Injections ; Male ; Netherlands ; Surveys and Questionnaires ; United States ; *Wounds and Injuries ; }, abstract = {A growing body of literature has implicated the role of disgust sensitivity in blood-injection-injury (BII) phobia. The present study sought to extend this line of research by investigating the structural relation between Rozin et al.'s [(2000). Disgust. In M. Lewis, J.M. Haviland (Eds.), Handbook of emotions. New York: Guilford Publications.] theoretical model of core and animal reminder disgust as they relate to BII fears in US (N = 162) and Dutch (N = 260) samples. Using confirmatory factor analysis (CFA), the hypothesized relation between the theoretical model of disgust and BII fears demonstrated good model fit in both samples. Consistent with previous findings on the differential relation between core and animal reminder disgust and BII fears [de Jong, P. J., & Merckelbach H. (1998). Blood-injection-injury phobia and fear of spiders: Domain specific individual differences in disgust sensitivity. Personality and Individual Differences, 24, 153-158], structural equation modeling (SEM) provided support for a domain specific relationship in both samples: animal reminder disgust was specifically related to the BII latent factor, whereas core disgust was not. The clinical and research implications regarding the relationships between disgust and BII fears across cultures are discussed.}, } @article {pmid16268082, year = {2005}, author = {Fugate, J}, title = {Art therapy with family caregivers of patients with cancer.}, journal = {Kentucky nurse}, volume = {53}, number = {4}, pages = {14}, pmid = {16268082}, issn = {0742-8367}, mesh = {*Adaptation, Psychological ; *Art Therapy ; Caregivers/*psychology ; Humans ; Neoplasms/*nursing ; }, abstract = {Walsh et al.'s (2004) study supported art therapy to reduce stress, decrease anxiety, and increase positive emotions. The results of this study can be used to support the group's utilization project to promote and educate nurses about the importance of creative arts programs with patients and family members and ways to help establish a creative arts program. One suggestion for future research would be to determine whether the severity of the illness of the patient plays a role in the effectiveness of the art therapy intervention. One feasibility issue for implementing art therapy in hospitals would be the cost of the materials, such as paper, watercolors, markers, and fabrics.}, } @article {pmid16262458, year = {2005}, author = {Shafer, A}, title = {Meta-analysis of the brief psychiatric rating scale factor structure.}, journal = {Psychological assessment}, volume = {17}, number = {3}, pages = {324-335}, doi = {10.1037/1040-3590.17.3.324}, pmid = {16262458}, issn = {1040-3590}, mesh = {Brief Psychiatric Rating Scale/*statistics & numerical data ; *Factor Analysis, Statistical ; Humans ; Psychometrics/methods ; Reproducibility of Results ; }, abstract = {A meta-analysis (N=17,620; k=26) of factor analyses of the Brief Psychiatric Rating Scale (BPRS) was conducted. Analysis of the 12 items from Overall et al.'s (J. E. Overall, L. E. Hollister, & P. Pichot, 1974) 4 subscales found support for his 4 subscales. Analysis of all 18 BPRS items found 4 components similar to those of Overall et al. In a 5-component solution, a 5th activation component emerged but was best supported among samples of schizophrenic patients. The first 4 components appear to form the core of the BPRS factor structure. Results of the meta-analysis suggest 5 subscales (with items in parentheses): Affect (anxiety, guilt, depression, somatic); Positive Symptoms (thought content, conceptual disorganization, hallucinatory behavior, grandiosity); Negative Symptoms (blunted affect, emotional withdrawal, motor retardation); Resistance (hostility, uncooperativeness, suspiciousness); and Activation (excitement, tension, mannerisms-posturing).}, } @article {pmid16249452, year = {2005}, author = {Rutter, MK and Meigs, JB and Sullivan, LM and D'Agostino, RB and Wilson, PW}, title = {Insulin resistance, the metabolic syndrome, and incident cardiovascular events in the Framingham Offspring Study.}, journal = {Diabetes}, volume = {54}, number = {11}, pages = {3252-3257}, doi = {10.2337/diabetes.54.11.3252}, pmid = {16249452}, issn = {0012-1797}, support = {N01-HC-25195/HC/NHLBI NIH HHS/United States ; R01-HL 073272/HL/NHLBI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Cardiovascular Diseases/*complications/*epidemiology ; Cross-Sectional Studies ; Female ; Humans ; Insulin Resistance/*physiology ; Male ; Metabolic Syndrome/*complications ; Middle Aged ; Odds Ratio ; Prospective Studies ; Risk Factors ; }, abstract = {The metabolic syndrome and insulin resistance have been related to incident cardiovascular disease (CVD), but it is uncertain if metabolic syndrome predicts CVD independent of insulin resistance. Our study sample included 2,898 people without diabetes or CVD at baseline. Metabolic syndrome was defined by the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) criteria. Insulin resistance was defined by the homeostasis model assessment (HOMA-IR) and by Gutt et al.'s insulin sensitivity index (ISI(0,120)). Age- and sex-adjusted proportional hazards regression models assessed the association of baseline metabolic syndrome and insulin resistance to 7-year CVD risk (186 events). Metabolic syndrome and both measures of insulin resistance were individually related to incident CVD (age- and sex-adjusted hazard ratio [HR] for metabolic syndrome [present versus absent]: 2.0 [95% CI 1.5-2.6], P = 0.0001; for HOMA-IR: 1.9 [1.2-2.9], P = 0.003; and for ISI(0,120) [both highest versus lowest quartile]: 0.5 [0.3-0.7], P = 0.001). In models adjusted for age, sex, LDL cholesterol, and smoking status and including metabolic syndrome, ISI(0,120) levels were independently related to incident CVD (0.5 [0.3-0.8], P = 0.004), whereas HOMA-IR levels were not (1.3 [0.8-2.1], P = 0.24); metabolic syndrome was associated with increased CVD risk in both models (HR 1.6, P < or = 0.007 in both). In conclusion, metabolic syndrome and ISI(0,120) but not HOMA-IR independently predicted incident CVD. Metabolic syndrome may not capture all the CVD risk associated with insulin resistance.}, } @article {pmid16239940, year = {2005}, author = {Cuddy, TM}, title = {Value of hospital libraries: the Fuld Campus study.}, journal = {Journal of the Medical Library Association : JMLA}, volume = {93}, number = {4}, pages = {446-449}, pmid = {16239940}, issn = {1558-9439}, mesh = {Classification/methods ; Humans ; Libraries, Hospital/*statistics & numerical data ; Library Surveys ; New Jersey ; }, abstract = {OBJECTIVE: The paper demonstrates the value of the Health Sciences Library/Fuld Campus to the organization and shows how responses from patrons aligned themselves with the categories of the taxonomy of contributions of library and information services (LIS) to hospital and academic health centers devised by Abels et al.

METHODS: Over a period of thirty-two months during 2001 to 2003, patrons' literature searches and interlibrary loans were followed up on by sending patrons letters, which included a question asking for feedback as to how the information was used. The comments from users were analyzed according to Abels et al.'s taxonomy of LIS contributions in hospital and academic health centers.

RESULTS: Results of this study substantiated previous research showing that health sciences LIS contributes to patient health care. Feedback also demonstrated other areas where LIS contributes to the mission and goals of the organization and how these align themselves with Abels et al.'s taxonomy.}, } @article {pmid16220487, year = {2006}, author = {Small, DS and Ten Have, TR and Joffe, MM and Cheng, J}, title = {Random effects logistic models for analysing efficacy of a longitudinal randomized treatment with non-adherence.}, journal = {Statistics in medicine}, volume = {25}, number = {12}, pages = {1981-2007}, doi = {10.1002/sim.2313}, pmid = {16220487}, issn = {0277-6715}, support = {P30-MH2129/MH/NIMH NIH HHS/United States ; R01-MH61892/MH/NIMH NIH HHS/United States ; R29 HL 59184/HL/NHLBI NIH HHS/United States ; }, mesh = {Humans ; *Logistic Models ; Longitudinal Studies ; Random Allocation ; Randomized Controlled Trials as Topic/statistics & numerical data ; }, abstract = {We present a random effects logistic approach for estimating the efficacy of treatment for compliers in a randomized trial with treatment non-adherence and longitudinal binary outcomes. We use our approach to analyse a primary care depression intervention trial. The use of a random effects model to estimate efficacy supplements intent-to-treat longitudinal analyses based on random effects logistic models that are commonly used in primary care depression research. Our estimation approach is an extension of Nagelkerke et al.'s instrumental variables approximation for cross-sectional binary outcomes. Our approach is easily implementable with standard random effects logistic regression software. We show through a simulation study that our approach provides reasonably accurate inferences for the setting of the depression trial under model assumptions. We also evaluate the sensitivity of our approach to model assumptions for the depression trial.}, } @article {pmid16210523, year = {2005}, author = {Robins, RW}, title = {Psychology. The nature of personality: genes, culture, and national character.}, journal = {Science (New York, N.Y.)}, volume = {310}, number = {5745}, pages = {62-63}, doi = {10.1126/science.1119736}, pmid = {16210523}, issn = {1095-9203}, mesh = {*Character ; Cross-Cultural Comparison ; *Culture ; *Ethnicity ; *Genes ; Humans ; *Personality/genetics ; Social Perception ; Stereotyping ; }, abstract = {Personality traits have a strong genetic foundation, are highly stable over time, and predict important societal outcomes, including health and occupational success. In his Perspective, Robins discusses Terracciano et al.'s finding that cultures differ somewhat in aggregate personality levels but those differences are not accurately reflected in stereotypes about national character. Robins discusses reasons why national stereotypes are inaccurate, as well as broader issues concerning individual and cultural sources of variation in personality.}, } @article {pmid16198082, year = {2006}, author = {Harrigan, JA and McGarrigle, BP and Sutter, TR and Olson, JR}, title = {Tissue specific induction of cytochrome P450 (CYP) 1A1 and 1B1 in rat liver and lung following in vitro (tissue slice) and in vivo exposure to benzo(a)pyrene.}, journal = {Toxicology in vitro : an international journal published in association with BIBRA}, volume = {20}, number = {4}, pages = {426-438}, doi = {10.1016/j.tiv.2005.08.015}, pmid = {16198082}, issn = {0887-2333}, support = {R01ES08148/ES/NIEHS NIH HHS/United States ; }, mesh = {Animals ; Aryl Hydrocarbon Hydroxylases/*biosynthesis/genetics ; Benzo(a)pyrene/*toxicity ; Biotransformation ; Carcinogens/*toxicity ; Cytochrome P-450 CYP1A1/*biosynthesis/genetics ; Cytochrome P-450 CYP1B1 ; Dose-Response Relationship, Drug ; Enzyme Induction ; Gene Expression/drug effects ; In Vitro Techniques ; Injections, Intraperitoneal ; Liver/*drug effects/enzymology/pathology ; Lung/*drug effects/enzymology/pathology ; Male ; Polychlorinated Dibenzodioxins/toxicity ; RNA, Messenger/metabolism ; Rats ; Rats, Sprague-Dawley ; }, abstract = {Cytochrome P-450s (CYPs) detoxify a wide variety of xenobiotics and environmental contaminants, but can also bioactivate carcinogenic polycyclic aromatic hydrocarbons, such as benzo(a)pyrene (BaP), to DNA-reactive species. The primary CYPs involved in the metabolism and bioactivation of BaP are CYP1A1 and CYP1B1. Furthermore, BaP can induce expression of CYP1A1 and CYP1B1 via the aryl hydrocarbon receptor. Induction of CYP1A1 and CYP1B1 by BaP in target (lung) and non-target (liver) tissues was investigated utilizing precision-cut rat liver and lung slices exposed to BaP in vitro. Tissue slices were also prepared from rats pretreated in vivo with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) to induce expression of CYP1A1 and CYP1B1. In addition, in vivo exposure studies were performed with BaP to characterize and validate the use of the in vitro tissue slice model. In vitro exposure of liver and lung slices to BaP resulted in a concentration-dependent increase in CYP1A1 and CYP1B1 mRNA and protein levels, which correlated directly with the exposure-related increase in BaP-DNA adduct levels observed previously in the tissue slices [Harrigan, J.A., Vezina, C.M., McGarrigle, B.P., Ersing, N., Box, H.C., Maccubbin, A.E., Olson, J.R., 2004. DNA adduct formation in precision-cut rat liver and lung slices exposed to benzo(a)pyrene. Toxicological Sciences 77, 307-314]. Pretreatment of animals in vivo with TCDD produced a marked induction of CYP1A1 and CYP1B1 expression in the tissue slices, which was similar to the levels of CYP1A1 and CYP1B1 mRNA achieved in liver and lung following in vivo treatment with BaP. Following in vitro exposure to BaP, the levels of CYP1A1 were greater in the lung than the liver, while following all exposures (in vitro and in vivo), the levels of CYP1B1 mRNA were greater in lung tissue compared to liver. The higher expression of CYP1A1 and CYP1B1 in the lung was associated with higher levels of BaP-DNA adducts in the lung slices (Harrigan et al.'s work) and together, these results may contribute to the tissue specificity of BaP-mediated carcinogenesis.}, } @article {pmid16194300, year = {2005}, author = {Heathcote, A and Elliott, D}, title = {Nonlinear dynamical analysis of noisy time series.}, journal = {Nonlinear dynamics, psychology, and life sciences}, volume = {9}, number = {4}, pages = {399-433}, pmid = {16194300}, issn = {1090-0578}, mesh = {Animals ; Artifacts ; Behavior ; Humans ; *Models, Psychological ; *Nonlinear Dynamics ; Reproducibility of Results ; Software ; }, abstract = {Empirical time series in the life sciences are often nonstationary and have small signal-to-noise ratios, making it difficult to accurately detect and characterize dynamical structure. The usual response to high noise is averaging, but time domain averaging is inappropriate, especially when the dynamics are nonlinear. We review alternative delay-space averaging methods based on the topology and short-term predictability of nonlinear dynamics and illustrate their application using the TISEAN software (Hegger, Kantz & Schreiber, 1999). The methods were applied to a Lorenz series, which resembles the dynamics found by Kelly, Heathcote, Heath and Longstaff (2001) in series of decision times. The Lorenz series was corrupted with up to 80% additive Gaussian noise, a lower signal-to-noise ratio than has been used in any previous test of these methods, but consistent with Kelly et al.'s data. Prediction methods performed the best for detecting nonstationarity and nonlinear dynamics, and optimal predictability provided an objective criterion for setting the parameters required by the analyses. Local linear filtering methods performed best for characterization, producing informative plots that revealed the nature of the underlying dynamics. These results suggest that a methodology based on delay-space averaging and prediction could be useful with noisy empirical data series.}, } @article {pmid16194253, year = {2005}, author = {Sawamura, K and Nakashima, Y and Inoue, M and Kurita, H}, title = {Short-term verbal memory deficits in patients with obsessive-compulsive disorder.}, journal = {Psychiatry and clinical neurosciences}, volume = {59}, number = {5}, pages = {527-532}, doi = {10.1111/j.1440-1819.2005.01409.x}, pmid = {16194253}, issn = {1323-1316}, mesh = {Age Factors ; Attention/physiology ; Disease Progression ; Female ; Humans ; Male ; Memory Disorders/*etiology/*psychology ; *Memory, Short-Term ; Mental Recall ; Middle Aged ; Obsessive-Compulsive Disorder/*complications/*psychology ; Recognition, Psychology ; Regression Analysis ; Verbal Learning/physiology ; }, abstract = {Recent neuropsychological studies have found deficits in the verbal memory of patients with obsessive-compulsive disorder. Difficulties in using organizational strategies were presumed to be the cause. Preceding studies did not look closely at their ability of feature detection of stimuli. Efficiency in feature detection is crucial to use the attributes or feature of stimuli as a clue in memory tasks. We examined verbal memory deficit and the ability of feature detection in Japanese patients with obsessive-compulsive disorder. We administered Iddon et al.'s verbal strategy task to 16 patients with obsessive-compulsive disorder and 16 healthy controls. The feature of Iddon et al.'s task was to include a phase that showed subjects the semantic structure of the task and timed each subject's analysis of the organization. Patients with obsessive-compulsive disorder were slower to classify stimuli words into semantic categories than were healthy controls. They recalled and recognized significantly fewer words than did healthy controls. In recall tasks, they used less organizational strategy than did healthy controls. Patients with obsessive-compulsive disorder were slower to analyze features of stimuli words than were healthy controls. This slowness possibly contributes to impaired memory performances that patients showed during the encoding process, since the efficient use of organizational strategies in limited time is difficult for them.}, } @article {pmid16190797, year = {2005}, author = {Faraone, SV and Biederman, J and Spencer, T and Michelson, D and Adler, L and Reimherr, F and Seidman, L}, title = {Atomoxetine and stroop task performance in adult attention-deficit/hyperactivity disorder.}, journal = {Journal of child and adolescent psychopharmacology}, volume = {15}, number = {4}, pages = {664-670}, doi = {10.1089/cap.2005.15.664}, pmid = {16190797}, issn = {1044-5463}, mesh = {Adult ; Atomoxetine Hydrochloride ; Attention Deficit Disorder with Hyperactivity/*drug therapy/*psychology ; Color Perception/drug effects ; Double-Blind Method ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; *Neuropsychological Tests ; Propylamines/adverse effects/*therapeutic use ; }, abstract = {OBJECTIVE: The aim of this study was to assess the efficacy of atomoxetine, a new and highly selective inhibitor of the norepinephrine transporter, for executive functioning in adults with attention-deficit/hyperactivity disorder (ADHD).

METHOD: Two identical studies using a double-blind, placebo-controlled, parallel design were conducted. Patients were adults (Study 1, n = 280; Study 2, n = 256) with Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV)-defined ADHD recruited by referral and advertising. They were randomized to 10 weeks of treatment with atomoxetine or placebo. Executive functions were measured by the Stroop task.

RESULTS: There was no evidence of cognitive deterioration associated with atomoxetine treatment. Atomoxetine treatment was associated with an improvement of the Stroop colorword score.

CONCLUSIONS: Our results provide further support for Spencer et al.'s (1998) report that atomoxetine improves inhibitory capacity, as measured by the Stroop task. The absence of cognitive deterioration from atomoxetine, along with improved performance in a subgroup of patients in this large study, supports the safety of atomoxetine in this regard and its potential for improving a significant source of impairment for adults with ADHD.}, } @article {pmid16170773, year = {2005}, author = {Gisselquist, D and Potterat, JJ}, title = {Questioning Wawer et al.'s estimated rate of sexual HIV transmission from persons with early HIV infections.}, journal = {The Journal of infectious diseases}, volume = {192}, number = {8}, pages = {1497-9; author reply 1499-1500}, doi = {10.1086/462431}, pmid = {16170773}, issn = {0022-1899}, mesh = {Acquired Immunodeficiency Syndrome/*transmission ; Disease Transmission, Infectious/statistics & numerical data ; HIV Infections/diagnosis/epidemiology/*prevention & control/*transmission ; Humans ; }, } @article {pmid16168505, year = {2006}, author = {Moore, RA and Gale, A and Morris, PH and Forrester, D}, title = {Theta phase locking across the neocortex reflects cortico-hippocampal recursive communication during goal conflict resolution.}, journal = {International journal of psychophysiology : official journal of the International Organization of Psychophysiology}, volume = {60}, number = {3}, pages = {260-273}, doi = {10.1016/j.ijpsycho.2005.06.003}, pmid = {16168505}, issn = {0167-8760}, mesh = {Adolescent ; Adult ; Analysis of Variance ; Attention/physiology ; *Conflict, Psychological ; Electroencephalography/methods ; Female ; Hippocampus/*physiology ; Humans ; Male ; Neocortex/*physiology ; Neural Pathways/*physiology ; Photic Stimulation ; Problem Solving/*physiology ; *Theta Rhythm ; }, abstract = {EEG theta coherence, EEG theta power and subjective levels of response were examined in a continuous monitoring target detection task where periodic goal conflicts were introduced as 34 participants progressed through a stimulus sequence leading to response. EEG theta coherence revealed increases in phase locking between cortical areas at specific task stages involving goal conflict. Theta power also increased at points of goal conflict. The temporal characteristics of subjective response (measured continuously throughout the task) indicated a delay between participants actually experiencing goal conflict and overt indications of conflict. The starting point for the study was based on a specific aspect of Gray and McNaughton's [Gray, J.A., McNaughton, N., 2000. The Neuropsychology of Anxiety: An Enquiry into the Functions of the Septo-Hippocampal System, 2nd ed. Oxford University Press, Oxford] behavioural inhibition system model-namely, septo-hippocampal system involvement in the resolution of goal conflicts. We drew on Gray and McNaughton's [Gray, J.A., McNaughton, N., 2000. The Neuropsychology of Anxiety: An Enquiry into the Functions of the Septo-Hippocampal system, 2nd ed. Oxford University Press, Oxford] suggestion that septo-hippocampal involvement in this process is reflected by EEG theta. While their theory explains many of our findings, we also drew upon Given's [Givens, B., 1996. Stimulus-evoked reseting of the dentate theta rhythm: relation to working memory. Neuroreport 8 (1), 159-163] proposal that the dentate theta rhythm is reset by behaviourally relevant stimuli. We made further proposals based on Makeig et al.'s [Makeig, S., Westerfield, M., Jung, T.-P., Enghoff, S., Townsend, J., Courchesne, E., Sejnowski, T.J., 2002. Dynamic brain sources of visual evoked responses. Science 295, 690-694] view that specific stimulus events invoke concurrent phase resetting and transient frequency domain coherence across different areas of neocortex. Relations with Go/NoGo event related potentials (P300 and N2; e.g., [Bokura, H., Yamaguchi, S., Kobayashi, S., 2001. Electrophysiological correlates of response inhibition in a Go/NoGo task. Clin. Neurophysiol. 112 (12), 2224-2232]) were also discussed, as well as parallels between our data and interpretation, and other theoretical models of theta (e.g., [Kahana, M.J., Selig, D., Madsen, J.R., 2001. Theta returns. Curr. Opin. Neurobiol. 11, 739-744]). Suggestions for further research were made.}, } @article {pmid16154626, year = {2005}, author = {He, JH}, title = {The allometry of leaf form in early plant ontogeny.}, journal = {Bulletin of mathematical biology}, volume = {67}, number = {6}, pages = {1333-1337}, doi = {10.1016/j.bulm.2005.02.005}, pmid = {16154626}, issn = {0092-8240}, mesh = {Fractals ; *Models, Biological ; Photosynthesis ; *Plant Development ; Plant Leaves/growth & development/metabolism ; Plants/metabolism ; Trees/growth & development/metabolism ; }, abstract = {A general allometric model between metabolic rate and body size has been derived for early plant ontogeny. The scaling exponent is (2+N/6)/3, where N is the cell's degree of freedom of motion. For early plant ontogeny N=2, our prediction agrees well with Sack et al.'s observation [Sack, L., Maranon, T., Grubb, P.J., 2002. Science 295, 1923].}, } @article {pmid16151823, year = {2005}, author = {Kose, KC}, title = {Response to Hafez et al.'s "Radiation exposure to the hands of orthopaedic surgeons: are we underestimating the risk?".}, journal = {Archives of orthopaedic and trauma surgery}, volume = {125}, number = {8}, pages = {575-576}, doi = {10.1007/s00402-005-0039-8}, pmid = {16151823}, issn = {0936-8051}, mesh = {Fluoroscopy/adverse effects ; Hand/*radiation effects ; Humans ; Occupational Exposure/*adverse effects ; Orthopedic Procedures/*adverse effects ; Radiation Injuries/*etiology ; }, } @article {pmid16144467, year = {2005}, author = {Muller, F}, title = {H(2)S-induced ectothermy: relevance to aging.}, journal = {Rejuvenation research}, volume = {8}, number = {3}, pages = {135-137}, doi = {10.1089/rej.2005.8.135}, pmid = {16144467}, issn = {1549-1684}, mesh = {Aging/*drug effects ; Animals ; *Biomedical Engineering ; Body Temperature/*drug effects ; Geriatrics/*methods ; Hydrogen Sulfide/*pharmacology ; }, abstract = {Many biogerontologists privately agree that "engineered negligible senescence" (ENS) is possible given enough time and resources. However, there is great discord on the time frame by which ENS will be achievable, with the more conservative voices (including this author) arguing for the first half of the next century. This means that most people alive today will not see this happen. Blackstone et al.'s recent report, showing that low levels of the toxic gas H(2)S can seemingly turn off the internal thermal rheostat of an endothermic, non-hibernating mammal, may make it possible for those alive today to live long enough (albeit at a slowed rate) until ENS comes about.}, } @article {pmid16133476, year = {2005}, author = {Ozer, H and Solak, S and Turanli, S and Baltaci, G and Colakoğlu, T and Bolukbasí, S}, title = {Intercondylar fractures of the distal humerus treated with the triceps-reflecting anconeus pedicle approach.}, journal = {Archives of orthopaedic and trauma surgery}, volume = {125}, number = {7}, pages = {469-474}, doi = {10.1007/s00402-005-0026-0}, pmid = {16133476}, issn = {0936-8051}, mesh = {Adolescent ; Adult ; Aged ; Female ; Follow-Up Studies ; Fracture Fixation, Internal/*methods ; Humans ; Humeral Fractures/physiopathology/*surgery ; Male ; Middle Aged ; Range of Motion, Articular/physiology ; Tendons/*surgery ; Treatment Outcome ; }, abstract = {INTRODUCTION: Treatment choice for displaced, intercondylar fractures of the distal humerus is open reduction and internal fixation (ORIF) through a posterior approach. The triceps-reflecting anconeus pedicle (TRAP) approach, combination of modified Kocher and Bryan-Morrey has been described as a conservative surgical exposure for fixation of the complex intercondylar fractures.

MATERIALS AND METHODS: Eleven patients with intercondylar fractures of the humerus operated with this approach were reviewed. The mean follow-up was 26 (14-40) months. The aetiology of injuries was mostly fall on the elbow. There were five females and six males and the average age of the patients was 58.3 years (range 16-70 years).

RESULTS: According to Müller et al.'s classification; five were Type C1, four were Type C2 and, two were Type C3. At the final follow-up; Type C1 and C2 fractures had a ROM of 116 degrees (range 95 degrees-140 degrees) and, Type C3 fractures had a ROM of 85 degrees which showed limitation of elbow motion. Average humerotrochlear angle is 93.4 degrees (range 90 degrees-98 degrees). Two patients had transient n. ulnaris paraesthesia and one had heterotopic ossification.

CONCLUSION: Our results demonstrate that TRAP approach is extensile enough in treating these complex fractures however both articular reconstruction and fixation can be easily managed without creating an olecranon fracture. No significant triceps weakness and dysfunction was observed after TRAP approach in the treatment of the intercondylar fractures of the humerus.}, } @article {pmid16131280, year = {2005}, author = {Radin, D}, title = {May et al.'s "anomalous anticipatory skin conductance response to acoustic stimuli".}, journal = {Journal of alternative and complementary medicine (New York, N.Y.)}, volume = {11}, number = {4}, pages = {587-588}, doi = {10.1089/acm.2005.11.587}, pmid = {16131280}, issn = {1075-5535}, mesh = {*Acoustic Stimulation ; Anxiety ; *Galvanic Skin Response/physiology ; Humans ; Monte Carlo Method ; *Reflex, Startle/physiology ; Research Design/*standards ; }, } @article {pmid16131247, year = {2005}, author = {Anderson, JR and Taatgen, NA and Byrne, MD}, title = {Learning to achieve perfect timesharing: architectural implications of Hazeltine, Teague, and Ivry (2002).}, journal = {Journal of experimental psychology. Human perception and performance}, volume = {31}, number = {4}, pages = {749-761}, doi = {10.1037/0096-1523.31.4.749}, pmid = {16131247}, issn = {0096-1523}, mesh = {*Cognition ; Humans ; *Learning ; Reaction Time ; Visual Perception ; }, abstract = {E. Hazeltine, D. Teague, and R. B. Ivry have presented data that have been interpreted as evidence against a central bottleneck. This article describes simulations of their Experiments 1 and 4 in the ACT-R cognitive architecture, which does possess a central bottleneck in production execution. The simulation model is capable of accounting for the emergence of near-perfect timesharing in Experiment 1 and the detailed data on the distribution of response times from Experiment 4. With practice, the central bottleneck in ACT-R will be reduced to a maximum of 50 ms (1 production cycle) and can often be much less, depending on timing of stages and variability in their times. The authors also show, with a mathematical analysis of E. Hazeltine et al.'s Experiment 2, that the expected dual costs for these kinds of highly practiced tasks will be small in many circumstances, often under 10 ms.}, } @article {pmid16128117, year = {2005}, author = {Bishop, K}, title = {Aromatherapy: does it work?.}, journal = {Kentucky nurse}, volume = {53}, number = {3}, pages = {23}, pmid = {16128117}, issn = {0742-8367}, abstract = {Results from Itai et al.'s (2000) study support a group utilization project to educate nurses regarding aromatherapy, so that nurses can implement it in their practice to reduce their patient's anxiety levels. A major feasibility issue would be the price tag; one must consider both the cost of paying for the training that the nurses would need and the materials needed to implement the practice or aromatherapy. Future research would be very valuable, especially if it replicated this study using a larger, more diverse sample of patients.}, } @article {pmid16116770, year = {2002}, author = {Wakefield, A}, title = {The changing 'shape' of the nursing station.}, journal = {Contemporary nurse}, volume = {13}, number = {2-3}, pages = {148-157}, doi = {10.5172/conu.13.2-3.148}, pmid = {16116770}, issn = {1037-6178}, mesh = {Attitude of Health Personnel ; Attitude to Health ; Authoritarianism ; Ceremonial Behavior ; Communication ; Ethnology ; Health Facility Environment/organization & administration ; Hospital Units/*organization & administration ; Humans ; *Interior Design and Furnishings ; *Interprofessional Relations ; Motivation ; *Nurse's Role ; Nursing Methodology Research ; *Nursing Staff, Hospital/organization & administration/psychology ; Organizational Culture ; Personal Space ; *Professional-Family Relations ; Social Control, Formal/methods ; Students, Nursing/psychology ; Symbolism ; United Kingdom ; Visitors to Patients/psychology ; Workplace/organization & administration ; }, abstract = {The Nursing Station is a puzzling structure fulfilling a variety of roles throughout the day. At times, it resembles a communal market place with staff standing around chatting. Yet, once a shift commences, regulatory characteristics emerge to control a person's entry and exit from the ward, by ensuring that they have an authentic reason for being there. This paper juxtaposes the role of the Nursing Station with Strauss et al.'s (1964) notion of shape. In this way, is intended to examine in detail how the Nursing Station can influence the normal and natural flow of work within a ward.}, } @article {pmid16082819, year = {2005}, author = {Garry, M and Wade, KA}, title = {Actually, a picture is worth less than 45 words: narratives produce more false memories than photographs do.}, journal = {Psychonomic bulletin & review}, volume = {12}, number = {2}, pages = {359-366}, pmid = {16082819}, issn = {1069-9384}, mesh = {Adult ; Humans ; *Narration ; *Portraits as Topic ; *Repression, Psychology ; *Visual Perception ; *Vocabulary ; }, abstract = {Most memory "implantation" studies have elicited false memories by using fake narratives. Recently, Wade, Garry, Read, and Lindsay (2002) showed that doctored photographs can be used to create false childhood memories in adults. Fifty percent of Wade et al.'s sample reported details of taking a childhood hot air balloon ride, although they had never been in a balloon. In this experiment, we investigated whether photos or narratives influence memory more than the other. We exposed subjects to either a fake photograph or a fake narrative of a childhood hot air balloon ride. Subjects tried to remember the false event and three real events over 1 week. Narratives were more likely to produce false memory reports than were photos. We offer a fluency-based account of our results and suggest that narratives promote more familiarity in subjects than do photographs.}, } @article {pmid16076675, year = {2005}, author = {Macmillan, NA and Rotello, CM and Verde, MF}, title = {On the importance of models in interpreting remember-know experiments: comments on Gardiner et al.'s (2002) meta-analysis.}, journal = {Memory (Hove, England)}, volume = {13}, number = {6}, pages = {607-621}, doi = {10.1080/09658210444000269}, pmid = {16076675}, issn = {0965-8211}, support = {R01 MH60274/MH/NIMH NIH HHS/United States ; }, mesh = {Bias ; Cognition ; Databases, Factual ; Decision Making ; Humans ; *Models, Psychological ; ROC Curve ; *Recognition, Psychology ; Signal Detection, Psychological ; }, abstract = {From a meta-analysis of recognition experiments using the remember-know-guess paradigm, Gardiner, Ramponi, and Richardson-Klavehn (2002) reported two findings that they viewed as evidence against the one-dimensional model for that paradigm: (1) Memory strength increased when know responses were added to remember responses, decreasing when guess responses were also included. (2) The accuracy of guess responses was correlated with the location of the old-new criterion in the one-dimensional model for the paradigm, implying that guesses were influenced by decision processes. We question both findings. The first result is contradicted by a signal-detection (SDT) analysis, which shows that both know and guess responses reduced estimated memory strength. The discrepancy results from the properties of A', the measure of accuracy used by Gardiner et al., which we argue is flawed. The second result follows directly from the one-dimensional model, in which accuracy and response criteria are fixed. The authors' reasons for rejecting the one-dimensional model are thus not persuasive, but it can nonetheless be rejected because ROC curves implied by the data are inconsistent with ROCs derived from ratings experiments. A two-dimensional SDT model (Rotello, Macmillan, & Reeder, 2004) accounts for both sets of data. The analysis illustrates the importance of models in interpreting remember--know data.}, } @article {pmid16060745, year = {2005}, author = {Bell, PA}, title = {Reanalysis and perspective in the heat--aggression debate.}, journal = {Journal of personality and social psychology}, volume = {89}, number = {1}, pages = {71-73}, doi = {10.1037/0022-3514.89.1.71}, pmid = {16060745}, issn = {0022-3514}, mesh = {*Aggression ; Hot Temperature ; Humans ; Linear Models ; *Models, Psychological ; Periodicity ; *Temperature ; *Violence ; }, abstract = {B. J. Bushman, M. C. Wang, and C. A. Anderson argued that a reanalysis of E. G. Cohn and J. Rotton's Minneapolis data shows no inverted-U curvilinear relationship between temperature and aggression. Although B. J. Bushman et al.'s claim of no general inverted-U trend in the data might well be supported statistically, more careful examination of the subset of the data most likely to include the hottest temperatures in the study may offer at least some support for the inverted-U relationship. Aggregating data to describe a general trend minimizes the influence of outliers that may reflect alternative relationships, and such alternatives may be important practically and theoretically.}, } @article {pmid16054729, year = {2005}, author = {Fjell, AM and Walhovd, KB}, title = {Age-sensitivity of P3 in high-functioning adults.}, journal = {Neurobiology of aging}, volume = {26}, number = {9}, pages = {1297-9; discussion 1301-6}, doi = {10.1016/j.neurobiolaging.2005.02.018}, pmid = {16054729}, issn = {0197-4580}, mesh = {Age Factors ; Aging/*physiology ; Brain/*physiology ; Event-Related Potentials, P300/*physiology ; Humans ; Neuropsychological Tests ; Reaction Time/physiology ; }, abstract = {In their interesting paper, Daffner et al. [Daffner KR, Ryan KK, Williams DM, Budson AE, Rentz DM, Scinto LFM, et al. Age-related differences in novelty and target processing among cognitively healthy high performing adults. Neurobiol Aging 2005;26:1283-95] argue that previous studies have found changes in ERP components in response to novel and target stimuli due to two methodological factors: (1) lack of control for differences in level of cognitive status between age groups, and (2) not controlling for a non-specific age-related processing difference for all stimulus types (standards, targets, and novel). The questions raised by Daffner et al. are interesting, but based on existing literature, their conclusion seems premature. In the following, we will present examples from empirical literature as well as re-analyses of some of our own work to illustrate problematic aspects of Daffner et al.'s position.}, } @article {pmid16049643, year = {2005}, author = {Gil, A}, title = {Repressing distress in childhood: a defense against health-related stress.}, journal = {Child psychiatry and human development}, volume = {36}, number = {1}, pages = {27-52}, pmid = {16049643}, issn = {0009-398X}, mesh = {Adaptation, Psychological ; Adolescent ; Child ; Chronic Disease/*psychology ; *Defense Mechanisms ; Depression/diagnosis/*etiology/*psychology ; *Health Status ; Humans ; *Repression, Psychology ; }, abstract = {This paper is a review of empirical investigations of the repressive adaptive style in youth. Studies were selected on the basis of their adherence to Weinberger et al.'s (J Abnorm Psychol 88: 369-380, 1979) paradigm, consisting of the interaction between a measure of distress and a measure of defensiveness to categorize repressors. The presence of a repressive style of adaptation was identified in adolescence, especially among pediatric populations. Adolescent repressors were found to exhibit characteristics similar to those identified among adult samples (i.e., self-deception, biased self-reports, and inhibition of signals of distress). Only one study focused on young repressors' autonomic reactivity, which is another main characteristic of a repressive adaptive style in adulthood. Methodological inconsistencies between child studies are highlighted and weaknesses in the psychometric properties of defensiveness measures in childhood are discussed. Future investigations should examine the impact of a repressive adaptive style on health outcomes and behaviors to see if adult health data associated with a repressive style of adaptation are replicable in childhood.}, } @article {pmid16001623, year = {2005}, author = {Safioleas, MC and Moulakakis, KG and Misiakos, EP and Lygidakis, NJ}, title = {Surgical management of choledochal cysts in adults.}, journal = {Hepato-gastroenterology}, volume = {52}, number = {64}, pages = {1030-1033}, pmid = {16001623}, issn = {0172-6390}, mesh = {Adult ; Aged ; Aged, 80 and over ; Anastomosis, Roux-en-Y ; *Biliary Tract Surgical Procedures ; Choledochal Cyst/classification/diagnosis/*surgery ; *Enterostomy ; Female ; Follow-Up Studies ; Humans ; Liver/*surgery ; Male ; Middle Aged ; Time Factors ; Treatment Outcome ; }, abstract = {BACKGROUND/AIMS: Choledochal cysts are congenital malformations of the pancreatico-biliary system. Some aspects of optimal surgical management of choledochal cysts remain controversial. The purpose of this paper is to present our series of 14 patients with choledochal cysts, analyzing surgical management and long-term results.

METHODOLOGY: Between January 1975 and December 2001, 15 adult patients with choledochal cysts were treated at our Department. Sex, age, clinical symptoms, associated diseases, surgical management and postoperative morbidity and mortality were reviewed. Choledochal cysts were classified according to the Alonso-Lej classification with Todani et al.'s, modification, based on radiographic and operative findings.

RESULTS: There were 15 patients, 6 males and 9 females, with an age ranging from 28 to 82 years and a mean age at the time of surgery 58.3 years. Seven patients had a solitary fusiform extrahepatic cyst (Type I), five patients had an extrahepatic supraduodenal diverticulum (Type II), one patient had a choledochocele (Type III), while two patients had a Type IVB cyst. Symptoms were vague and intermittent. Recurrent upper abdominal pain, jaundice, fever, nausea and vomiting were the most common findings, usually occurring in combination. Two patients presented with cholestatic cirrhosis. Five patients had laboratory evidence of hepatocellular dysfunction and two patients had hyperamylasemia. A variety of operations was performed such as cystoduodenostomy, cyst excision and hepaticojejunostomy, cyst excision and choledochoduodenostomy. Postoperative follow-up ranged from 30 months to 12 years in all patients except of two patients who were lost to follow-up.

CONCLUSIONS: Total or partial excision of the choledochal cysts is the optimal treatment because of the lower incidence of postoperative complications and the better survival rate after the operation.}, } @article {pmid15993828, year = {2005}, author = {Rodway, P}, title = {The modality shift effect and the effectiveness of warning signals in different modalities.}, journal = {Acta psychologica}, volume = {120}, number = {2}, pages = {199-226}, doi = {10.1016/j.actpsy.2005.05.002}, pmid = {15993828}, issn = {0001-6918}, mesh = {Acoustic Stimulation/methods ; Analysis of Variance ; Attention/*physiology ; Auditory Perception/*physiology ; Cues ; Discrimination, Psychological/physiology ; Female ; Humans ; Male ; Photic Stimulation/methods ; Psychomotor Performance/physiology ; Reaction Time/*physiology ; Signal Detection, Psychological/*physiology ; Students/psychology ; Visual Perception/*physiology ; }, abstract = {Which is better, a visual or an auditory warning signal? Initial findings suggested that an auditory signal was more effective, speeding reaction to a target more than a visual warning signal, particularly at brief foreperiods [Bertelson, P., & Tisseyre, F. (1969). The time-course of preparation: confirmatory results with visual and auditory warning signals. Acta Psychologica, 30. In W.G. Koster (Ed.), Attention and Performance II (pp. 145-154); Davis, R., & Green, F. A. (1969). Intersensory differences in the effect of warning signals on reaction time. Acta Psychologica, 30. In W.G. Koster (Ed.), Attention and Performance II (pp. 155-167)]. This led to the hypothesis that an auditory signal is more alerting than a visual warning signal [Sanders, A. F. (1975). The foreperiod effect revisited. Quarterly Journal of Experimental Psychology, 27, 591-598; Posner, M. I., Nissen, M. J., & Klein, R. M. (1976). Visual dominance: an information-processing account of its origins and significance. Psychological Review, 83, 157-171]. Recently [Turatto, M., Benso, F., Galfano, G., & Umilta, C. (2002). Nonspatial attentional shifts between audition and vision. Journal of Experimental Psychology: Human Perception and Performance, 28, 628-639] found no evidence for an auditory warning signal advantage and showed that at brief foreperiods a signal in the same modality as the target facilitated responding more than a signal in a different modality. They accounted for this result in terms of the modality shift effect, with the signal exogenously recruiting attention to its modality, and thereby facilitating responding to targets arriving in the modality to which attention had been recruited. The present study conducted six experiments to understand the cause of these conflicting findings. The results suggest that an auditory warning signal is not more effective than a visual warning signal. Previous reports of an auditory superiority appear to have been caused by using different locations for the visual warning signal and visual target, resulting in the target arriving at an unattended location when the foreperiod was brief. Turatto et al.'s results were replicated with a modality shift effect at brief foreperiods. However, it is also suggested that previous measures of the modality shift effect may still have been confounded by a location cuing effect.}, } @article {pmid15975944, year = {2005}, author = {Reverberi, C and Toraldo, A and D'Agostini, S and Skrap, M}, title = {Better without (lateral) frontal cortex? Insight problems solved by frontal patients.}, journal = {Brain : a journal of neurology}, volume = {128}, number = {Pt 12}, pages = {2882-2890}, doi = {10.1093/brain/awh577}, pmid = {15975944}, issn = {1460-2156}, mesh = {Adult ; Aged ; Brain Injury, Chronic/diagnostic imaging/pathology/*psychology ; Case-Control Studies ; Cues ; Female ; Humans ; Intuition ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Neuropsychological Tests ; Prefrontal Cortex/diagnostic imaging/*pathology/physiopathology ; *Problem Solving ; Tomography, X-Ray Computed ; }, abstract = {A recently proposed theory on frontal lobe functions claims that the prefrontal cortex, particularly its dorso-lateral aspect, is crucial in defining a set of responses suitable for a particular task, and biasing these for selection. This activity is carried out for virtually any kind of non-routine tasks, without distinction of content. The aim of this study is to test the prediction of Frith's 'sculpting the response space' hypothesis by means of an 'insight' problem-solving task, namely the matchstick arithmetic task. Starting from Knoblich et al.'s interpretation for the failure of healthy controls to solve the matchstick problem, and Frith's theory on the role of dorsolateral frontal cortex, we derived the counterintuitive prediction that patients with focal damage to the lateral frontal cortex should perform better than a group of healthy participants on this rather difficult task. We administered the matchstick task to 35 patients (aged 26-65 years) with a single focal brain lesion as determined by a CT or an MRI scan, and to 23 healthy participants (aged 34-62 years). The findings seemed in line with theoretical predictions. While only 43% of healthy participants could solve the most difficult matchstick problems ('type C'), 82% of lateral frontal patients did so (Fisher's exact test, P < 0.05). In conclusion, the combination of Frith's and Knoblich et al.'s theories was corroborated.}, } @article {pmid15969356, year = {2005}, author = {Frencham, KA and Fox, AM and Maybery, MT}, title = {Neuropsychological studies of mild traumatic brain injury: a meta-analytic review of research since 1995.}, journal = {Journal of clinical and experimental neuropsychology}, volume = {27}, number = {3}, pages = {334-351}, doi = {10.1080/13803390490520328}, pmid = {15969356}, issn = {1380-3395}, mesh = {Brain Injuries/*physiopathology ; Cognition Disorders/*physiopathology ; Neuropsychological Tests/*statistics & numerical data ; Time Factors ; }, abstract = {A meta-analysis conducted by Binder, Rohling and Larrabee established a relationship between mild traumatic brain injury (TBI) and small reductions in cognitive functioning in individuals assessed more than 3 months post-injury. As a follow-up, this study summarized similar research that (1) was published since the previous meta-analysis, and (2) included data collected at any stage post-injury. An extensive literature search revealed 17 suitable studies from which effect sizes were aggregated. The overall effect size was g = 0.32, p < .001. Speed of processing measures had the largest effect, g = 0.47, p < .001. The merging of post-acute effect sizes with those reported in Binder et al.'s review yielded a nonsignificant result, g = 0.11. Time since injury was found to be a significant moderator variable, with effect sizes tending to zero with increasing time post injury.}, } @article {pmid15961253, year = {2005}, author = {Deisboeck, TS and Mansury, Y and Guiot, C and Degiorgis, PG and Delsanto, PP}, title = {Insights from a novel tumor model: Indications for a quantitative link between tumor growth and invasion.}, journal = {Medical hypotheses}, volume = {65}, number = {4}, pages = {785-790}, doi = {10.1016/j.mehy.2005.04.014}, pmid = {15961253}, issn = {0306-9877}, support = {CA 085139/CA/NCI NIH HHS/United States ; CA 09502/CA/NCI NIH HHS/United States ; CA 113004/CA/NCI NIH HHS/United States ; }, mesh = {Cell Count ; Disease Progression ; Humans ; *Models, Biological ; Neoplasm Invasiveness/*physiopathology ; Neoplasms/*physiopathology ; }, abstract = {Both the lack of nutrient supply and rising mechanical stress exerted by the microenvironment appear to be able to cause discrepancies between the actual, observed tumor mass and that predicted by West et al.'s [A general model for ontogenetic growth. Nature 2001;413:628-31] universal growth model. Using our previously developed model we hypothesize here, that (1) solid tumor growth and cell invasion are linked, not only qualitatively but also quantitatively, that (2) the onset of invasion marks the time point when the tumor's cell density reaches a compaction maximum, and that (3) tumor cell invasion, reduction of mechanical confinement and angiogenesis can all contribute to an increase in the actual tumor mass m towards the level m(W) predicted by West et al.'s universal growth curve. These novel insights contribute to our understanding of tumorigenesis and thus may have important implications not only for experimental cancer research but also be of value for clinical purposes such as for predictions of tumor growth dynamics and treatment impact.}, } @article {pmid15960076, year = {2005}, author = {Arifin, DR and Palmer, AF}, title = {Stability of liposome encapsulated hemoglobin dispersions.}, journal = {Artificial cells, blood substitutes, and immobilization biotechnology}, volume = {33}, number = {2}, pages = {113-136}, doi = {10.1081/bio-200055874}, pmid = {15960076}, issn = {1073-1199}, mesh = {Blood Substitutes/*pharmacokinetics ; *Drug Stability ; Hemoglobins/*administration & dosage ; Humans ; Liposomes/*pharmacokinetics ; Membranes, Artificial ; Particle Size ; Permeability ; Stress, Mechanical ; }, abstract = {The demand for artificial blood substitutes in cases of elective surgeries, trauma, and civilian mass catastrophes increases every day. However, few studies have been done to characterize the mechanical stability of blood substitutes, especially liposome encapsulated hemoglobin (LEHb) dispersions. In this work, the stability of LEHb dispersions was investigated by fitting Jung et al.'s liposome size distribution model to experimentally measured LEHb size distributions [6] (produced via extrusion) using asymmetric flow field-flow fractionation coupled with multi-angle static light scattering. The effective bending constant (KB) and radius of curvature (R0) of each liposome dispersion were regressed from the size distribution fits. The model was found to be in agreement with the size distributions of LEHbs extruded through 400, 200 and 100 nm pore diameter membranes, but not in agreement with LEHbs extruded through 80 and 50 nm pore diameter membranes. Although the magnitude of KB fluctuated, we deduced a general trend for KB to decrease with decreasing pore diameter, and increasing initial Hb concentration. LEHbs extruded through 400nm pore diameter membranes were stabilized by the spontaneous curvature effect, while those extruded through 80 and 50 nm pore diameter membranes were mostly stabilized by thermal undulations, regardless of the initial Hb concentration. For LEHb dispersions extruded through 200 and 100 nm pore diameter membranes, there was a transition of stabilization mechanism from spontaneous curvature to thermal undulations with increasing initial Hb concentration. Taken together, these results suggest that moderate Hb encapsulation might actually impart better mechanical stability to LEHb dispersions extruded through 200 and 100 nm pore diameter membranes.}, } @article {pmid15959634, year = {2005}, author = {Dorow, C and Sander, FG}, title = {Development of a model for the simulation of orthodontic load on lower first premolars using the finite element method.}, journal = {Journal of orofacial orthopedics = Fortschritte der Kieferorthopadie : Organ/official journal Deutsche Gesellschaft fur Kieferorthopadie}, volume = {66}, number = {3}, pages = {208-218}, doi = {10.1007/s00056-005-0416-5}, pmid = {15959634}, issn = {1434-5293}, mesh = {Bicuspid/*physiology ; Computer Simulation ; Dental Stress Analysis/*methods ; Finite Element Analysis ; Humans ; *Models, Biological ; *Orthodontic Appliances ; Periodontal Ligament/*physiology ; Stress, Mechanical ; }, abstract = {AIM: This study was undertaken to calculate the stress in the tooth, surrounding periodontal ligament, and in the alveolar bone when a lower first premolar is subjected to intrusion or torque movement using a constant moment. Root resorptions occur even when very low forces and moments are used in orthodontic therapy. It is therefore of great interest to determine and measure the stress that occurs under particular treatment conditions in the periodontal ligament.

MATERIAL AND METHODS: In this study, three finite element calculations were carried out with a realistic 3D model developed by CT data that consisted of a lower premolar, the surrounding periodontal ligament and alveolar bone. In close reference to the in-vivo experiments carried out by Faltin et al. in São Paulo, Brazil, our model was subjected to an intrusive force on the premolar of 0.5 N and a lingual root torque of 3 Nmm.

RESULTS: The three main stress directions and hydrostatic stress were quantified in all the surrounding tissues, revealing that the hydrostatic stress profile in the periodontal ligament correlated closely with resorption findings in Faltin et al.'s patients. Resorption occurred in the experimental study in Brazil when the hydrostatic stress exceeded capillary blood pressure in the periodontal ligament.

CONCLUSION: We maintain that hydrostatic stress represents a suitable indicator for potential root resorptions caused by higher forces and moments, making it a helpful tool in the development of new orthodontic appliances. We must of course mention that there are many factors other than forces that are responsible for resorptions. But at the moment, only the force can be influenced by the orthodontist.}, } @article {pmid15951089, year = {2005}, author = {de Leon, J and Diaz, FJ and Josiassen, RC and Cooper, TB and Simpson, GM}, title = {Does clozapine decrease smoking?.}, journal = {Progress in neuro-psychopharmacology & biological psychiatry}, volume = {29}, number = {5}, pages = {757-762}, doi = {10.1016/j.pnpbp.2005.04.031}, pmid = {15951089}, issn = {0278-5846}, support = {MH-47162/MH/NIMH NIH HHS/United States ; }, mesh = {Adult ; Antipsychotic Agents/*therapeutic use ; Biomarkers ; Clozapine/*therapeutic use ; Cotinine/blood ; Double-Blind Method ; Female ; Haloperidol/therapeutic use ; Humans ; Male ; Psychiatric Status Rating Scales ; Schizophrenia/complications ; Sex Characteristics ; Smoking/blood/*drug therapy ; Time Factors ; }, abstract = {McEvoy et al.'s study in 1999, which used cotinine levels but had limited power, suggested that clozapine treatment may be associated with a mild smoking decrease (particularly when plasma clozapine levels are > 150 ng/ml). Some naturalistic studies also suggest that clozapine treatment may be associated with a mild smoking decrease. The present study included 38 schizophrenic daily smokers from a double-blind clozapine trial. Five analyses were tested for significant decreases in plasma cotinine levels from a haloperidol baseline to: (1) the end of clozapine trials regarding clozapine doses (100, 300 or 600 mg/day), (2) the end of the clozapine trial where the highest plasma clozapine level was achieved, (3) the end of the clozapine trial where a clozapine level in the 150-450 ng/ml range was achieved, (4) the end of the first clozapine trial regardless of clozapine dose, and (5) the end of the last clozapine trial in the study. The first and straightforward analysis by dose showed no clozapine effects on smoking. The second and the third analyses (an attempt to mimic the design by McEvoy et al. [McEvoy, J.P., Freudenreich, O., Wilson, W.H., 1999. Smoking and therapeutic response to clozapine in patients with schizophrenia. Biol. Psychiat. 46, 125-129.]) also indicated that there was not a significant effect of clozapine on smoking. The fourth and five analyses were also negative. None of the five analyses in our clozapine trial demonstrated that clozapine had major effects on smoking. This study cannot rule out that in some subjects, clozapine treatment may be associated with a small decrease in smoking. New prospective longitudinal studies using repeated cotinine and clozapine levels are needed to explore whether clozapine may reduce smoking in some patients.}, } @article {pmid15941115, year = {2005}, author = {Cameron, P}, title = {Oddities in Kirkpatrick, et al.'s study of children of lesbian mothers.}, journal = {Psychological reports}, volume = {96}, number = {2}, pages = {397-407}, doi = {10.2466/pr0.96.2.397-407}, pmid = {15941115}, issn = {0033-2941}, mesh = {Child ; Child Behavior Disorders/*psychology ; Child, Preschool ; Female ; *Homosexuality, Female ; Humans ; Male ; *Parenting ; Play and Playthings ; Sexual Behavior/*psychology ; }, abstract = {Kirkpatrick, et al.'s 1976 study of what happened to 20 lesbians' children has received considerable attention, apparently later being matched with 20 heterosexuals' children. In 2004, Kirkpatrick generally acknowledged Schumm's caution that her findings are less impressive than are needed, yet, Kirkpatrick stated her "early findings have been reinforced" and that "no evidence of differences in the children grouped by the mother's sexual orientation" have been documented by subsequent research. Close examination of the data of these studies indicates that children from 13 lesbian mothers were compared with children from 13 divorced heterosexuals. Further, there are contradictions between the published reports regarding the nature of samples and various findings. Analysis of Kirkpatrick, et al.'s study suggests that children do less well when raised by homosexual parents.}, } @article {pmid15941105, year = {2005}, author = {Newman, RG}, title = {Comment on Soar, et al.'s case study of problems and use of Ecstasy.}, journal = {Psychological reports}, volume = {96}, number = {2}, pages = {322}, doi = {10.2466/pr0.96.2.322-322}, pmid = {15941105}, issn = {0033-2941}, mesh = {Cognition Disorders/*etiology ; Humans ; *N-Methyl-3,4-methylenedioxyamphetamine ; Substance-Related Disorders/*complications/*psychology ; Time Factors ; }, abstract = {This case report provides no basis for drawing any conclusions regarding possible adverse effects of use of Ecstasy.}, } @article {pmid15919159, year = {2006}, author = {Maisto, SA and Zywiak, WH and Connors, GJ}, title = {Course of functioning 1 year following admission for treatment of alcohol use disorders.}, journal = {Addictive behaviors}, volume = {31}, number = {1}, pages = {69-79}, doi = {10.1016/j.addbeh.2005.04.008}, pmid = {15919159}, issn = {0306-4603}, support = {K02 AA13262/AA/NIAAA NIH HHS/United States ; }, mesh = {Adaptation, Psychological ; Adult ; Alcohol-Related Disorders/epidemiology/psychology/*rehabilitation ; Female ; Follow-Up Studies ; Humans ; Life Change Events ; Male ; Middle Aged ; Multivariate Analysis ; New York/epidemiology ; Rhode Island/epidemiology ; *Temperance/psychology ; Treatment Outcome ; }, abstract = {Research on alcohol treatment outcomes has the potential to advance knowledge about how treatment combines with other variables to influence post treatment course of functioning. The purpose of this study was to replicate and extend [Connors, G. J., Maisto, S. A., & Zywiak, W. H. (1996). Understanding relapse in the broader context of post-treatment functioning. Addiction, 91 (Suppl.), S173-S189] test of a multivariate model of course by testing the model's fit to data from a larger sample and the use of stronger statistical methods. The participants were 400 men and women presenting for alcohol treatment in two cities in the US. These individuals completed a pretreatment (baseline) assessment battery at treatment initiation and then completed follow-up assessments bimonthly for a period of 1 year. The model included pretreatment, treatment (months 1-6), and post-baseline (months 1-6) factors to predict alcohol use (percent days abstinent, drinks/drinking day, and total number drinks/month, all for months 7-12). The application of structural equation modeling methods revealed that the model fit the data adequately for all three dependent variables, with the major significant findings of direct effects of treatment setting, coping skills, and the mediation of treatment effects through coping skills. Overall, the data replicated several findings from the Connors et al.'s study and point to the importance of investigating the mechanisms underlying treatment effects and the mediation of treatment effects by coping skills in future research.}, } @article {pmid15904729, year = {2005}, author = {Roblot, C and Ferrandière, M and Bierlaire, D and Fusciardi, J and Mercier, C and Laffon, M}, title = {[Impact of Cormack and Lehane's grade on Intubating Laryngeal Mask Airway Fastrach using: a study in gynaecological surgery].}, journal = {Annales francaises d'anesthesie et de reanimation}, volume = {24}, number = {5}, pages = {487-491}, doi = {10.1016/j.annfar.2005.02.017}, pmid = {15904729}, issn = {0750-7658}, mesh = {Adult ; Aged ; Airway Obstruction/complications/diagnosis ; Anesthesia, Obstetrical ; Anthropometry ; Body Mass Index ; Female ; Genital Diseases, Female/complications ; *Gynecologic Surgical Procedures ; Humans ; Laryngeal Masks/*statistics & numerical data ; Middle Aged ; Obesity/complications ; Predictive Value of Tests ; Prospective Studies ; *Severity of Illness Index ; }, abstract = {OBJECTIVE: To evaluate the impact of Cormack and Lehane grade on the Intubating Laryngeal Mask Airway (LMA-Fastrach) using in women.

STUDY DESIGN: Open prospective study.

PATIENTS: The study included 115 scheduled gynaecologic surgery women.

METHODS: An LMA-Fastrach was systematically performed in patients with a Cormack's grade > or =3 or when Arne's score was > or =7 whatever the Cormack. After induction of anaesthesia and neuromuscular blockade, Cormack's grade was assessed and LMA-Fastrach was inserted. Proper insertion was confirmed by the easiness of assisted ventilation and the normal aspect of the capnographic curve. Intubation through the LMA-Fastrach was carried out with the specific kit's endotracheal tube. More than two attempts were considered as a failure of the technique and an alternative method was performed. The following parameters were noted: age, weight, height, clinical predictors for difficult intubation (Arne et al.'s score), number of LMA-Fastrach insertion, ventilation efficiency through LMA-Fastrach, successful intubation with LMA-Fastrach and oesophageal intubation.

RESULTS: Ventilation through the LMA-Fastrach was efficient in 97%. The success rate of intubation was 94.8% (86% on the first attempt). The success rate of ventilation and intubation were not statistically different according to the different Cormack's grades. The obesity (BMI>30) did not change the success rate of ventilation and intubation through the LMA-Fastrach.

CONCLUSION: In women with either predicted or unpredicted difficult intubation, the success rates of ventilation and intubation through the LMA-Fastrach don't seem to be influenced by Cormack grade and obesity.}, } @article {pmid15902674, year = {2005}, author = {Sethabouppha, H and Kane, C}, title = {Caring for the seriously mentally ill in Thailand: Buddhist family caregiving.}, journal = {Archives of psychiatric nursing}, volume = {19}, number = {2}, pages = {44-57}, doi = {10.1016/j.apnu.2005.02.004}, pmid = {15902674}, issn = {0883-9417}, mesh = {Adaptation, Psychological ; Adult ; Aged ; Attitude to Health/*ethnology ; Buddhism/*psychology ; Caregivers/economics/education/*psychology ; Cost of Illness ; Educational Status ; Empathy ; Family/*ethnology ; Female ; Home Nursing/economics/*psychology ; Hospitalization/statistics & numerical data ; Humans ; Income/statistics & numerical data ; Male ; Middle Aged ; Models, Psychological ; Nursing Methodology Research ; Qualitative Research ; Religion and Psychology ; Schizophrenia/*ethnology/prevention & control ; Social Support ; Stress, Psychological/ethnology/etiology/prevention & control ; Thailand ; }, abstract = {The purpose of this study was to explore the lived experiences from Thai Buddhist family caregivers of seriously mentally ill relatives to understand their perspectives about Buddhist caregiving. A phenomenological study of 15 Thai Buddhist family caregivers was conducted following Cohen et al.'s process for analysis. Analysis of the interviews revealed five major themes: caregiving is Buddhist belief, caregiving is compassion, caregiving is management, caregiving is acceptance, and caregiving is suffering. Although suffering from the problems posed by mental illness permeated their lives, Thai Buddhist caregivers were able to continue to maintain compassion, management, and acceptance in caregiving to their seriously mentally ill relatives. A model of Thai Buddhist caregiving, constructed from the five major themes, is presented.}, } @article {pmid15896816, year = {2006}, author = {Henry, JD and Phillips, LH and Crawford, JR and Theodorou, G and Summers, F}, title = {Cognitive and psychosocial correlates of alexithymia following traumatic brain injury.}, journal = {Neuropsychologia}, volume = {44}, number = {1}, pages = {62-72}, doi = {10.1016/j.neuropsychologia.2005.04.011}, pmid = {15896816}, issn = {0028-3932}, mesh = {Adolescent ; Adult ; Affective Symptoms/*etiology ; Aged ; Brain Injuries/*physiopathology/psychology ; Cognition/*physiology ; Female ; Humans ; Male ; Middle Aged ; Neuropsychological Tests ; Personality Inventory ; Psychiatric Status Rating Scales ; Psychometrics ; Quality of Life ; Regression Analysis ; *Social Behavior ; Surveys and Questionnaires ; }, abstract = {Changes in emotional and social behaviour are considered to be amongst the most common and debilitating consequences of traumatic brain injury (TBI). Little is known of the effects of TBI on alexithymia, which refers to impairment in aspects of understanding emotions. In the current study TBI patients (N=28) were compared with demographically matched healthy controls (N=31) on the Toronto Alexithymia Scale-20 (TAS-20), a measure that taps three distinct characteristics of the alexithymia concept; difficulty in identifying emotions, difficulty in describing emotions and externally oriented thinking. Patients and controls also completed measures of anxiety, depression, quality of life, and measures of fluency to assess executive function. Patients showed greater levels of alexithymia, in terms of difficulty identifying emotions and reduced introspection. Difficulty in identifying emotions was associated with poorer quality of life, even when depression and anxiety were controlled. Difficulty in identifying emotions was also uniquely associated with executive function deficits. Thus, although studies typically focus on aspects of cognitive change following head injury, these results lend support to Becerra et al.'s (Becerra, R., Amos, A., & Jongenelis, S. (2002). Organic alexithymia: a study of acquired emotional blindness. Brain Injury, 16, 633-645.) notion of an 'organic alexithymia', and suggest that more attention should be focused upon assessment of emotional change post-head injury.}, } @article {pmid15888635, year = {2005}, author = {Minkler, M}, title = {Community-based research partnerships: challenges and opportunities.}, journal = {Journal of urban health : bulletin of the New York Academy of Medicine}, volume = {82}, number = {2 Suppl 2}, pages = {ii3-12}, pmid = {15888635}, issn = {1099-3460}, mesh = {*Community Health Planning ; *Community Participation ; *Cooperative Behavior ; Ethics, Research ; Global Health ; *Health Services Research/ethics ; Humans ; Informed Consent ; Organizational Case Studies ; *Urban Health ; }, abstract = {The complexity of many urban health problems often makes them ill suited to traditional research approaches and interventions. The resultant frustration, together with community calls for genuine partnership in the research process, has highlighted the importance of an alternative paradigm. Community-based participatory research (CBPR) is presented as a promising collaborative approach that combines systematic inquiry, participation, and action to address urban health problems. Following a brief review of its basic tenets and historical roots, key ways in which CBPR adds value to urban health research are introduced and illustrated. Case study examples from diverse international settings are used to illustrate some of the difficult ethical challenges that may arise in the course of CBPR partnership approaches. The concepts of partnership synergy and cultural humility, together with protocols such as Green et al.'s guidelines for appraising CBPR projects, are highlighted as useful tools for urban health researchers seeking to apply this collaborative approach and to deal effectively with the difficult ethical challenges it can present.}, } @article {pmid15869338, year = {2005}, author = {Weisz, JR and Weersing, VR and Henggeler, SW}, title = {Jousting with straw men: comment on Westen, Novotny, and Thompson-Brenner (2004).}, journal = {Psychological bulletin}, volume = {131}, number = {3}, pages = {418-26, discussion 427-33}, doi = {10.1037/0033-2909.131.3.418}, pmid = {15869338}, issn = {0033-2909}, support = {AA122202/AA/NIAAA NIH HHS/United States ; DA015844/DA/NIDA NIH HHS/United States ; DA10079/DA/NIDA NIH HHS/United States ; DA17487/DA/NIDA NIH HHS/United States ; R01 MH 064503-01A1/MH/NIMH NIH HHS/United States ; R01 MH 60663/MH/NIMH NIH HHS/United States ; R01 MH57347/MH/NIMH NIH HHS/United States ; R01-MH068806/MH/NIMH NIH HHS/United States ; R21-MH63302/MH/NIMH NIH HHS/United States ; }, mesh = {Empirical Research ; Humans ; Mental Disorders/*psychology/*therapy ; Psychotherapy/*methods ; Randomized Controlled Trials as Topic/*standards ; Research Design/standards ; Treatment Outcome ; }, abstract = {Empirically supported treatments (ESTs) do not cure every patient, and the randomized trial is not a flawless methodology. Upon these often-noted and widely accepted points, D. Westen, C. M. Novotny, and H. Thompson-Brenner (2004a; see record 2004-15935-005) built a critique of ESTs and EST research. However, important work developing effective, clinically relevant treatments for serious problems was omitted from the Westen et al. (2004a) review. Little documentation was offered for the purported "assumptions" of EST methodology that Westen et al. (2004a) criticized; and different review standards were applied to studies supporting versus those disagreeing with Westen et al.'s (2004a) views. Finally, the correlational research designs proposed as a remedy by Westen et al. (2004a) have far more serious weaknesses than randomized trials, thoughtfully applied to real-world clinical care.}, } @article {pmid15865947, year = {2005}, author = {Langner, R and Maercker, A}, title = {Complicated grief as a stress response disorder: evaluating diagnostic criteria in a German sample.}, journal = {Journal of psychosomatic research}, volume = {58}, number = {3}, pages = {235-242}, doi = {10.1016/j.jpsychores.2004.09.012}, pmid = {15865947}, issn = {0022-3999}, mesh = {*Adaptation, Psychological ; Adjustment Disorders/*diagnosis/psychology ; Adult ; Algorithms ; Defense Mechanisms ; Diagnostic and Statistical Manual of Mental Disorders ; Family/psychology ; Female ; *Grief ; Humans ; Male ; Middle Aged ; Personality Inventory/*statistics & numerical data ; Psychometrics/statistics & numerical data ; Reproducibility of Results ; Socioeconomic Factors ; Stress, Psychological/*complications ; }, abstract = {BACKGROUND: Complicated grief has been described as a diagnosis candidate for DSM-V. On the basis of the stress response theory, Horowitz et al. [Am J Psychiatry 154 (1997) 904-10] characterized complicated grief as a combination of sustained intrusion, avoidance, and maladaptation symptoms following the loss of a close person. This study aimed at evaluating diagnostic criteria based on the stress response model of complicated grief.

METHODS: We administered a symptom list derived from Horowitz et al.'s operationalization to a sample of bereaved persons and evaluated the psychometric properties of the symptom criteria and symptom category subscales. Using this symptom list and other self-report measures of psychopathology and normal grief reactions, we examined a German sample consisting of 75 participants who had lost either siblings, children, parents, or spouses, on average, 5.4 years prior to the study.

RESULTS: Analyses confirmed the classification of symptoms into intrusion, avoidance, and failure-to-adapt categories with only minimal reordering (two symptom criteria). The symptom category subscales showed favourable psychometric characteristics, receiver operating characteristic (ROC) analyses indicated high diagnostic accuracy of the symptom criteria, and predictive validation revealed a meaningful correlational pattern to standard measures of divergent psychopathology and normal grief reactions.

CONCLUSIONS: The application of a stress response operationalization of complicated grief is supported.}, } @article {pmid15850479, year = {2005}, author = {Liu, H and Tarima, S and Borders, AS and Getchell, TV and Getchell, ML and Stromberg, AJ}, title = {Quadratic regression analysis for gene discovery and pattern recognition for non-cyclic short time-course microarray experiments.}, journal = {BMC bioinformatics}, volume = {6}, number = {}, pages = {106}, pmid = {15850479}, issn = {1471-2105}, support = {P20 RR016481/RR/NCRR NIH HHS/United States ; R01 AG016824/AG/NIA NIH HHS/United States ; 1P20RR16481-03/RR/NCRR NIH HHS/United States ; AG-016824-23/AG/NIA NIH HHS/United States ; }, mesh = {Algorithms ; Analysis of Variance ; Animals ; Artificial Intelligence ; Cluster Analysis ; Computational Biology/*methods ; Computer Graphics ; Computer Simulation ; Data Interpretation, Statistical ; Databases, Genetic ; Gene Expression Profiling/*methods ; Gene Expression Regulation ; Gene Library ; Genomics/*methods ; Humans ; Models, Theoretical ; Olfactory Receptor Neurons/metabolism ; Oligonucleotide Array Sequence Analysis/*methods ; Pattern Recognition, Automated ; Probability ; Regression Analysis ; Reproducibility of Results ; Sequence Alignment ; Sequence Analysis, DNA ; *Software ; Time Factors ; }, abstract = {BACKGROUND: Cluster analyses are used to analyze microarray time-course data for gene discovery and pattern recognition. However, in general, these methods do not take advantage of the fact that time is a continuous variable, and existing clustering methods often group biologically unrelated genes together.

RESULTS: We propose a quadratic regression method for identification of differentially expressed genes and classification of genes based on their temporal expression profiles for non-cyclic short time-course microarray data. This method treats time as a continuous variable, therefore preserves actual time information. We applied this method to a microarray time-course study of gene expression at short time intervals following deafferentation of olfactory receptor neurons. Nine regression patterns have been identified and shown to fit gene expression profiles better than k-means clusters. EASE analysis identified over-represented functional groups in each regression pattern and each k-means cluster, which further demonstrated that the regression method provided more biologically meaningful classifications of gene expression profiles than the k-means clustering method. Comparison with Peddada et al.'s order-restricted inference method showed that our method provides a different perspective on the temporal gene profiles. Reliability study indicates that regression patterns have the highest reliabilities.

CONCLUSION: Our results demonstrate that the proposed quadratic regression method improves gene discovery and pattern recognition for non-cyclic short time-course microarray data. With a freely accessible Excel macro, investigators can readily apply this method to their microarray data.}, } @article {pmid15847228, year = {2005}, author = {Multhaup, KS and Johnson, MD and Tetirick, JC}, title = {The wane of childhood amnesia for autobiographical and public event memories.}, journal = {Memory (Hove, England)}, volume = {13}, number = {2}, pages = {161-173}, doi = {10.1080/09608210344000652}, pmid = {15847228}, issn = {0965-8211}, mesh = {Adolescent ; Adult ; Age Factors ; Aged ; Amnesia/*psychology ; Humans ; *Life Change Events ; Memory/*physiology ; Middle Aged ; Psychophysiology ; *Public Sector ; Surveys and Questionnaires ; Time Factors ; }, abstract = {We modified Bruce, Dolan, and Phillips-Grant's (2000) threshold procedure for determining the wane of childhood amnesia. In two experiments, undergraduates labelled childhood events (e.g., your first permanent tooth came in) as know or recollect memories and estimated their age at the event's occurrence. In both studies the estimated transition from mostly know memories to mostly recollect memories was roughly 4.7 years. This transition estimate was replicated in a sample of adults (ages 24-65 years) with both Bruce et al.'s event-generation task and the Experiment 1a questionnaire. By contrast, in two experiments a transition estimate of roughly 6 years was found for undergraduates' memories of public events (e.g., the Challenger explosion). The wane of childhood amnesia appears to occur around 4.7 years.}, } @article {pmid15825481, year = {2005}, author = {Park, J and Park, DC and Marks, RJ and El-Sharkawi, MA}, title = {Recovery of image blocks using the method of alternating projections.}, journal = {IEEE transactions on image processing : a publication of the IEEE Signal Processing Society}, volume = {14}, number = {4}, pages = {461-474}, doi = {10.1109/tip.2004.842354}, pmid = {15825481}, issn = {1057-7149}, mesh = {*Algorithms ; Artificial Intelligence ; *Computer Graphics ; Image Enhancement/*methods ; Image Interpretation, Computer-Assisted/*methods ; Information Storage and Retrieval/*methods ; Numerical Analysis, Computer-Assisted ; Pattern Recognition, Automated/methods ; Reproducibility of Results ; Sensitivity and Specificity ; *Signal Processing, Computer-Assisted ; }, abstract = {A technique for block-loss restoration in block-based image and video coding, dubbed recovery of image blocks using the method of alternating projections (RIBMAP), is developed. The algorithm is based on orthogonal projections onto constraint sets in a Hilbert space. For the recovery of a linear dimension N size block, a total of 8N vectors are extracted from the surrounding area of an N x N missing block. These vectors form a library from which the best matching spatial information for the missing block is extracted. Recovery vectors, including both undamaged and restored damaged pixels, are introduced. The vectors are used to find highly correlated information relating to the lost pixels. To assure continuity with the surrounding undamaged area, three additional convex constraints are formulated. Adherance to these sets is imposed using alternating projections. Simulation results using orthogonal projections demonstrate that RIBMAP recovers spatial structure faithfully. Simulation comparisons with other procedures are presented: Ancis and Giusto's hybrid edge-based average-median interpolation technique, Sun and Kwok's projections onto convex sets-based method, Hemami and Meng's interblock correlation interpolation approach, Shirani et al.'s modified interblock correlation interpolation scheme, and Alkachouh and Bellanger's fast discrete cosine transformation-based spatial domain interpolation algorithm. Characteristic of the results are those of the "Lena" JPEG image when one fourth of periodically spaced blocks in the image have errors. The peak signal-to-noise ratio of the restored image is 28.68, 29.99, 31.86, 31.69, 31.57, and 34.65 dB using that of Ancis and Giusto, Sun and Kwok, Hemami and Meng, Shirani et al., Alkachouh and Bellanger, and RIPMAP, respectively.}, } @article {pmid15804845, year = {2005}, author = {Díaz-Morales, JF and Sánchez-López, MP}, title = {Composite scales of morningness and preferences: preliminary validity data in Peruvian undergraduates.}, journal = {Ergonomics}, volume = {48}, number = {4}, pages = {354-363}, doi = {10.1080/0014013042000327661}, pmid = {15804845}, issn = {0014-0139}, mesh = {Adolescent ; Adult ; Attention ; Circadian Rhythm/*physiology ; Female ; Humans ; Life Style ; Male ; *Personal Satisfaction ; Peru ; Psychometrics/*instrumentation ; Sleep ; Students/*psychology ; *Surveys and Questionnaires ; Time ; Universities ; *Wakefulness ; }, abstract = {The aim of this study is to offer preliminary results about the validity of the composite morningness scale (CS) and the early/late preferences scale (PS) in a Peruvian sample. The relationship of both scales with the preferred rising and retiring times was analysed, along with the level of self-reported alertness. In Bohle et al.'s (2001) work, the relationship between morningness and preferred rising and retiring times was higher over the weekend than on weekdays. This difference explained the dispositional nature of morningness, due to the possible lesser influence of time schedules over the weekend in individuals' preferences. This result is replicated in a group of 139 Peruvian undergraduates, aged between 18 and 29 years (M = 21.73), of whom 78.4% were women. The relationship between morningness and (actual) normal rising and retiring times on weekdays and over the weekend is considered. The results partially confirm Bohle et al.'s (2001) hypothesis about preferred rising and retiring times and their relationship with the PS, and actual rising time and its relationship with the CS and PS. The differences in the level of self-reported alertness between morning, intermediate and evening-oriented groups provide support for the validity of both scales. Finally, the scores of CS and PS in Peruvian undergraduates are similar to those found by Smith et al. (2002) in university students from six countries.}, } @article {pmid15804239, year = {2005}, author = {de Seze, J and Delalande, S and Michelin, E and Gauvrit, JY and Mackowiak, MA and Ferriby, D and Stojkovic, T and Defebvre, L and Pruvo, JP and Vermersch, P}, title = {Brain MRI in late-onset multiple sclerosis.}, journal = {European journal of neurology}, volume = {12}, number = {4}, pages = {241-244}, doi = {10.1111/j.1468-1331.2004.01103.x}, pmid = {15804239}, issn = {1351-5101}, mesh = {Aged ; Brain/*pathology ; Case-Control Studies ; *Evaluation Studies as Topic ; Female ; Follow-Up Studies ; Humans ; Magnetic Resonance Imaging/*methods/standards ; Male ; Middle Aged ; Multiple Sclerosis/*diagnosis/epidemiology/pathology ; Observer Variation ; Prospective Studies ; Reference Values ; Reproducibility of Results ; Sensitivity and Specificity ; }, abstract = {Multiple sclerosis (MS) with clinical onset after 50 years of age is unusual (between 1 and 6%) and is frequently misdiagnosed. Furthermore, brain magnetic resonance imaging (MRI) abnormalities are frequently observed in subjects over 50 years of age. The aim of this study was to describe brain MRI in late-onset MS to evaluate the sensitivity and specificity of radiological MS criteria in patients aged over 50 years. We evaluated the brain MRI of 20 patients with onset of MS after 50 years of age. We compared these MRI with 26 controls matched for age, sex and vascular risk factors. MRI were blindly analysed by two neuroradiologists according to Paty et al.'s [Neurology38 (1988) 180] criteria, Fazekas et al.'s [Neurology38 (1988) 1822] criteria and Barkhof et al.'s [Brain120 (1997) 2059] criteria. The mean age at MRI scanning was 58 years. Sensitivity was 90% for Paty et al.'s criteria, 80% for Fazekas et al.'s criteria and 85% for Barkhof et al.'s criteria. Specificity was 54% for Paty et al.'s criteria, 69% for Fazekas et al.'s criteria and 65% for Barkhof et al.'s criteria. Barkhof et al.'s criteria are less specific in older patients than in young patients. We suggest that spinal cord MRI and cerebrospinal fluid analysis should be systematically performed in suspected late-onset MS in order to increase the specificity of the diagnosis.}, } @article {pmid15783296, year = {2005}, author = {Garnham, A and Oakhill, JV}, title = {Accounting for belief bias in a mental model framework: comment on Klauer, Musch, and Naumer (2000).}, journal = {Psychological review}, volume = {112}, number = {2}, pages = {509-18; discussion 519-20}, doi = {10.1037/0033-295X.112.2.509}, pmid = {15783296}, issn = {0033-295X}, mesh = {Culture ; Humans ; *Logic ; *Problem Solving ; Psychology/*methods ; }, abstract = {K. C. Klauer, J. Musch, and B. Naumer (2000; see record 2000-02818-008) presented a general multinomial model of belief bias effects in syllogistic reasoning. They claimed to map a particular mental model account of belief bias (J. V. Oakhill, P. N. Johnson-Laird, & A. Garnham, 1989; see record 1989-38845-001)) onto this model and to show empirically that it is incorrect. The authors argue that this mental model account does not map onto the multinomial model and that it can account for the data presented by Klauer et al. (Experiments 1-4). The authors further argue that additional data Klauer et al. presented in support of a new model of their own (Experiments 5-8) are explained by this mental model account. The mental model account is, therefore, refuted neither by Klauer et al.'s theoretical analysis nor by any of the results they presented. Furthermore, the account can accommodate more recent findings on belief bias in a more satisfactory way than can alternative models that have been proposed.}, } @article {pmid15778571, year = {2005}, author = {Lee, PS and Sohn, JN and Lee, YM and Park, EY and Park, JS}, title = {[A correlational study among perceived stress, anger expression, and depression in cancer patients].}, journal = {Taehan Kanho Hakhoe chi}, volume = {35}, number = {1}, pages = {195-205}, doi = {10.4040/jkan.2005.35.1.195}, pmid = {15778571}, issn = {1598-2874}, mesh = {Adult ; Aged ; Aged, 80 and over ; *Anger ; Depression/*etiology/psychology ; Female ; Humans ; Male ; Middle Aged ; Neoplasms/*psychology ; *Stress, Psychological ; }, abstract = {PURPOSE: This study was to identify the relationship between perceived stress, anger expression, and level of depression in cancer patients.

METHOD: A cross-sectional descriptive study design was used. Data was collected by questionnaires from 185 in- and out-patients who were diagnosed with cancer at 3 university hospitals and the National Cancer Center using Spielberger et al.'s Anger Expression Scale, Cohen, Kamarch & Mermelstein's Perceived Stress, and Derogatise's SCL-90. The data was analyzed using descriptive statistics, Pearson correlation coefficient, and stepwise multiple regression with SAS/PC.

RESULT: The perceived stress in cancer patients indicated a significant positive correlation to anger-in(r=.288, p=.000), anger-out(r=.232, p=.001), and depression(r=.68, p=.000), but no significant correlation to anger-control. The anger-in of cancer patients showed a significant positive relationship to anger-out(r=.53, p=.000), and depression(r=.383, p=.000), but no significant correlation to anger-control. Anger-out showed a significantly negative correlation to anger-control(r=-.248, p=.001) and a positive correlation to depression(r=.240, p=.001). The most significant predictor which influenced depression in cancer patients was perceived stress, followed by anger-in and hobby, and these factors explained their depression with a variance of 54%.

CONCLUSION: These results suggested that cancer patients with a high degree of perceived stress are likely to be high in anger-out and anger-in. Perceived stress and anger-in are major factors which affect depression in cancer patients.}, } @article {pmid15770121, year = {2005}, author = {Burden, MJ and Jacobson, SW and Sokol, RJ and Jacobson, JL}, title = {Effects of prenatal alcohol exposure on attention and working memory at 7.5 years of age.}, journal = {Alcoholism, clinical and experimental research}, volume = {29}, number = {3}, pages = {443-452}, doi = {10.1097/01.alc.0000156125.50577.ec}, pmid = {15770121}, issn = {0145-6008}, support = {P50-AA07606/AA/NIAAA NIH HHS/United States ; R01-AA09524/AA/NIAAA NIH HHS/United States ; S06-RR08167/RR/NCRR NIH HHS/United States ; }, mesh = {Adult ; Attention/*drug effects ; Central Nervous System Depressants/*adverse effects ; Child ; Ethanol/*adverse effects ; Female ; Fetal Alcohol Spectrum Disorders/pathology/psychology ; Humans ; Memory, Short-Term/*drug effects ; Neuropsychological Tests ; Pregnancy ; *Prenatal Exposure Delayed Effects ; Psychomotor Performance/drug effects ; }, abstract = {BACKGROUND: A broad range of attentional and neuropsychological impairments have been demonstrated in children with fetal alcohol exposure. This study was designed to investigate which specific aspects of attentional function are most directly affected by moderate to heavy doses of prenatal alcohol exposure.

METHODS: A total of 337 black children who were aged 7.5 years and recruited prospectively to overrepresent prenatal alcohol exposure at moderate to heavy levels were assessed on a diverse battery of neuropsychological tests. Principal components analyses were used to replicate and extend Mirsky et al.'s (1991) four-component model of attention. The relation of prenatal alcohol exposure to empirically derived attentional constructs was examined.

RESULTS: Both the replicated and the extended attentional models produced solutions similar to the original Mirsky et al. model, reflecting elements of encode (working memory), shift, and focused and sustained attention, as well as a distinct component reflecting impulsivity. Adverse effects of maternal drinking across pregnancy were found primarily for working memory, and these effects were exacerbated when mothers were aged 30 or older at the time of the child's birth.

CONCLUSIONS: These data confirm previous studies using diverse methods that suggest that working memory may be the most important aspect of attention that is adversely affected by prenatal alcohol exposure.}, } @article {pmid15766334, year = {2005}, author = {van den Bosch, JE and Kalkman, CJ and Vergouwe, Y and Van Klei, WA and Bonsel, GJ and Grobbee, DE and Moons, KG}, title = {Assessing the applicability of scoring systems for predicting postoperative nausea and vomiting.}, journal = {Anaesthesia}, volume = {60}, number = {4}, pages = {323-331}, doi = {10.1111/j.1365-2044.2005.04121.x}, pmid = {15766334}, issn = {0003-2409}, mesh = {Antiemetics/*administration & dosage ; Area Under Curve ; Calibration ; Health Status Indicators ; Humans ; *Patient Selection ; Postoperative Nausea and Vomiting/*etiology ; Risk Assessment ; Sensitivity and Specificity ; }, abstract = {We have validated two scoring systems for predicting postoperative nausea and vomiting, derived by Apfel et al. and Koivuranta et al. from 1388 adult inpatients undergoing a wide range of surgical procedures. The predictive accuracy of the scoring systems was evaluated in terms of the ability to discriminate between patients with and without postoperative nausea and vomiting (discrimination) and agreement between observed and predicted outcomes (calibration). Discrimination and calibration were less than expected based on previous reports, with both scoring systems providing risk predictions that were too extreme. The area under the ROC curve was 0.63 for Apfel et al.'s scoring system and 0.66 for Koivuranta et al.'s scoring system. Neither of the scoring systems provided a risk threshold for administering anti-emetic prophylaxis that yielded satisfying results in terms of predictive values, sensitivity and specificity. Hence, in their original forms, the scoring systems do not guarantee accurate prediction of the risk of postoperative nausea and vomiting in other patient populations. Koivuranta et al.'s scoring system appears to be more robust across different populations.}, } @article {pmid15755253, year = {2005}, author = {Ho, MH and Regenwetter, M and Niederée, R and Heyer, D}, title = {An alternative perspective on von Winterfeldt et al.'s (1997) test of consequence monotonicity.}, journal = {Journal of experimental psychology. Learning, memory, and cognition}, volume = {31}, number = {2}, pages = {365-373}, doi = {10.1037/0278-7393.31.2.365}, pmid = {15755253}, issn = {0278-7393}, mesh = {*Choice Behavior ; Humans ; *Judgment ; Models, Psychological ; *Psychological Tests ; Psychological Theory ; }, abstract = {D. von Winterfeldt, N.-K. Chung, R. D. Luce, and Y. Cho (1997) provided several tests for consequence monotonicity of choice or judgment, using certainty equivalents of gambles. The authors reaxiomatized consequence monotonicity in a probabilistic framework and reanalyzed von Winterfeldt et al.'s main experiment via a bootstrap method. Their application offers new insights into consequence monotonicity as well as into von Winterfeldt et al.'s 3 experimental paradigms: judged certainty equivalents (JCE), QUICKINDIFF, and parameter estimation by sequential testing (PEST). For QUICKINDIFF, the authors found no indication of violations of "random consequence monotonicity." This sharply contrasts the findings of von Winterfeldt et al., who concluded that axiom violations were the most pronounced under that procedure. The authors found potential evidence for violations in JCE and certainty equivalents derived from PEST.}, } @article {pmid15752028, year = {2005}, author = {Deng, J and Viers, BD and Esker, AR and Anseth, JW and Fuller, GG}, title = {Phase behavior and viscoelastic properties of trisilanolcyclohexyl-POSS at the air/water interface.}, journal = {Langmuir : the ACS journal of surfaces and colloids}, volume = {21}, number = {6}, pages = {2375-2385}, doi = {10.1021/la047568w}, pmid = {15752028}, issn = {0743-7463}, abstract = {A trisilanol polyhedral oligomeric silsesquioxane (POSS), trisilanolcyclohexyl-POSS (TCyP), has recently been reported to undergo a series of phase transitions from traditional Langmuir monolayers to unique rodlike hydrophobic aggregates in multilayer films that are different from "collapsed" morphologies seen in other systems at the air/water interface. This paper focuses on the phase transitions and morphology of films varying in average thickness from monolayers to trilayers and the corresponding viscoelastic properties of trisilanolcyclohexyl-POSS molecules at the air/water interface by means of surface pressure-area per molecule (Pi-A) isotherms, Brewster angle microscopy (BAM), and interfacial stress rheometry (ISR) measurements. The morphology studies by BAM reveal that the TCyP monolayer can collapse into different 3D structures by homogeneous or heterogeneous nucleation mechanisms. For homogeneous nucleation, analysis by Vollhardt et al.'s nucleation and growth model reveals that TCyP collapse is consistent with instantaneous nucleation with hemispherical edge growth at Pi = 3.7 mN.m(-1). Both surface storage (Gs') and loss (Gs") moduli obtained by ISR reveal three different non-Newtonian flow regimes that correlate with phase transitions in the Pi-A isotherms: (A) A viscous liquidlike "monolayer"; (B) a "biphasic regime"between a liquidlike viscous monolayer and a more rigid trilayer; and (C) an elastic solidlike "trilayer". These observations provide interesting insights into collapse mechanisms and structures in Langmuir films.}, } @article {pmid15746272, year = {2005}, author = {Marshall, WL and Yates, PM}, title = {Comment on Mailloux et al.'s (2003) Study "Dosage of treatment to sexual offenders: are we overprescribing?".}, journal = {International journal of offender therapy and comparative criminology}, volume = {49}, number = {2}, pages = {221-4; discussion 225-9}, doi = {10.1177/0306624X04268351}, pmid = {15746272}, issn = {0306-624X}, mesh = {Cognitive Behavioral Therapy/classification/methods ; Combined Modality Therapy ; Humans ; Male ; Needs Assessment ; Ontario ; Outcome and Process Assessment, Health Care ; Prisoners/*psychology ; Psychotherapy/*methods ; Risk Assessment ; Secondary Prevention ; Sex Offenses/classification/prevention & control/*psychology ; }, } @article {pmid15745862, year = {2005}, author = {Schimmack, U and Oishi, S and Diener, E}, title = {Individualism: a valid and important dimension of cultural differences between nations.}, journal = {Personality and social psychology review : an official journal of the Society for Personality and Social Psychology, Inc}, volume = {9}, number = {1}, pages = {17-31}, doi = {10.1207/s15327957pspr0901_2}, pmid = {15745862}, issn = {1088-8683}, mesh = {Bias ; *Cross-Cultural Comparison ; Humans ; *Individuality ; Personal Construct Theory ; Psychometrics/statistics & numerical data ; *Social Identification ; *Social Values ; Statistics as Topic ; }, abstract = {Oyserman, Coon, and Kemmelmeier's (2002) meta-analysis suggested problems in the measurement of individualism and collectivism. Studies using Hofstede's individualism scores show little convergent validity with more recent measures of individualism and collectivism. We propose that the lack of convergent validity is due to national differences in response styles. Whereas Hofstede statistically controlled for response styles, Oyserman et al.'s meta-analysis relied on uncorrected ratings. Data from an international student survey demonstrated convergent validity between Hofstede's individualism dimension and horizontal individualism when response styles were statistically controlled, whereas uncorrected scores correlated highly with the individualism scores in Oyserman et al.'s meta-analysis. Uncorrected horizontal individualism scores and meta-analytic individualism scores did not correlate significantly with nations' development, whereas corrected horizontal individualism scores and Hofstede's individualism dimension were significantly correlated with development. This pattern of results suggests that individualism is a valid construct for cross-cultural comparisons, but that the measurement of this construct needs improvement.}, } @article {pmid15709875, year = {2005}, author = {Greenwald, AG}, title = {A reminder about procedures needed to reliably produce perfect timesharing: comment on Lien, McCann, Ruthruff, and Proctor (2005).}, journal = {Journal of experimental psychology. Human perception and performance}, volume = {31}, number = {1}, pages = {221-225}, doi = {10.1037/0096-1523.31.1.221}, pmid = {15709875}, issn = {0096-1523}, support = {MH-01533/MH/NIMH NIH HHS/United States ; MH-41328/MH/NIMH NIH HHS/United States ; MH-57672/MH/NIMH NIH HHS/United States ; }, mesh = {*Choice Behavior ; Humans ; *Psychomotor Performance ; *Reaction Time ; Reproducibility of Results ; }, abstract = {M.-C. Lien, R. S. McCann, E. Ruthruff, and R. W. Proctor (2005) argued that simultaneous ideomotor-compatible choice tasks cannot be perfectly timeshared. Their conclusion is limited in generalizability for 2 reasons: (a) Their experiments did not include procedures that previous research has shown to be necessary for obtaining perfect timesharing (motivating subjects to perform the 2 tasks rapidly and simultaneously; homogeneous blocks of simultaneous stimuli for the 2 tasks), and (b) their experiments included a procedure that previous research has shown to interfere with perfect timesharing of simultaneous tasks (within-block variation of task interstimulus intervals). Also discussed here are problems in M.-C. Lien et al.'s (2005) analysis of slopes relating Task 2 latency to Task 1 latency and their advocacy of a central bottleneck theory that may not be disconfirmable.}, } @article {pmid15702966, year = {2005}, author = {Wagenmakers, EJ and Farrell, S and Ratcliff, R}, title = {Human cognition and a pile of sand: a discussion on serial correlations and self-organized criticality.}, journal = {Journal of experimental psychology. General}, volume = {134}, number = {1}, pages = {108-116}, pmid = {15702966}, issn = {0096-3445}, support = {R37 MH044640/MH/NIMH NIH HHS/United States ; K05 MH001891/MH/NIMH NIH HHS/United States ; R37-MH44640/MH/NIMH NIH HHS/United States ; K05-MH01891/MH/NIMH NIH HHS/United States ; R01 AG017083/AG/NIA NIH HHS/United States ; }, mesh = {*Cognition ; Humans ; Psychological Theory ; Reaction Time ; *Self Concept ; }, abstract = {Recently, G. C. Van Orden, J. G. Holden, and M. T. Turvey (2003) proposed to abandon the conventional framework of cognitive psychology in favor of the framework of nonlinear dynamical systems theory. Van Orden et al. presented evidence that "purposive behavior originates in self-organized criticality" (p. 333). Here, the authors show that Van Orden et al.'s analyses do not test their hypotheses. Further, the authors argue that a confirmation of Van Orden et al.'s hypotheses would not have constituted firm evidence in support of their framework. Finally, the absence of a specific model for how self-organized criticality produces the observed behavior makes it very difficult to derive testable predictions. The authors conclude that the proposed paradigm shift is presently unwarranted.}, } @article {pmid15675000, year = {2004}, author = {Shera, CA and Tubis, A and Talmadge, CL}, title = {Do forward- and backward-traveling waves occur within the cochlea? Countering the critique of Nobili et al.}, journal = {Journal of the Association for Research in Otolaryngology : JARO}, volume = {5}, number = {4}, pages = {349-359}, pmid = {15675000}, issn = {1525-3961}, support = {R29 DC03094/DC/NIDCD NIH HHS/United States ; R01 DC003687/DC/NIDCD NIH HHS/United States ; R01 DC003094/DC/NIDCD NIH HHS/United States ; R01 DC03687/DC/NIDCD NIH HHS/United States ; R29 DC003094/DC/NIDCD NIH HHS/United States ; }, mesh = {Animals ; Cochlea/*physiology ; Humans ; Labyrinthine Fluids/*physiology ; *Models, Biological ; Otoacoustic Emissions, Spontaneous/*physiology ; }, abstract = {The question of whether or not forward- and backward-traveling waves occur within the cochlea constitutes a long-standing controversy in cochlear mechanics recently brought to the fore by the problem of understanding otoacoustic emissions. Nobili and colleagues articulate the opposition to the traveling-wave viewpoint by arguing that wave-equation formulations of cochlear mechanics fundamentally misrepresent the hydrodynamics of the cochlea [e.g., Nobili et al. (2003) J. Assoc. Res. Otolaryngol. 4:478-494]. To correct the perceived deficiencies of the wave-equation formulation, Nobili et al. advocate an apparently altogether different approach to cochlear modeling--the so-called "hydrodynamic" or "Green's function" approach--in which cochlear responses are represented not as forward- and backward-traveling waves but as weighted sums of the motions of individual basilar membrane oscillators, each interacting with the others via forces communicated instantaneously through the cochlear fluids. In this article, we examine Nobili and colleagues' arguments and conclusions while attempting to clarify the broader issues at stake. We demonstrate that the one-dimensional wave-equation formulation of cochlear hydrodynamics does not misrepresent long-range fluid coupling in the cochlea, as claimed. Indeed, we show that the long-range component of Nobili et al.'s three-dimensional force propagator is identical to the hydrodynamic Green's function representing a one-dimensional tapered transmission line. Furthermore, simulations that Nobili et al. use to discredit wave-equation formulations of cochlear mechanics (i.e., cochlear responses to excitation at a point along the basilar membrane) are readily reproduced and interpreted using a simple superposition of forward- and backward-traveling waves. Nobili and coworkers' critique of wave-equation formulations of cochlear mechanics thus appears to be without compelling foundation. Although the traveling-wave and hydrodynamic formulations impose strikingly disparate conceptual and computational frameworks, the two approaches ultimately describe the same underlying physics.}, } @article {pmid15673493, year = {2004}, author = {O'Bryant, SE and O'Jile, JR}, title = {Attenuating demographic influences on verbal fluency and animal naming in a psychiatric sample.}, journal = {Applied neuropsychology}, volume = {11}, number = {4}, pages = {210-214}, doi = {10.1207/s15324826an1104_6}, pmid = {15673493}, issn = {0908-4282}, mesh = {Adolescent ; Adult ; Aged ; Aging/psychology ; Culture ; Demography ; Education ; Ethnicity ; Female ; Humans ; Male ; Mental Disorders/*psychology ; Middle Aged ; *Neuropsychological Tests ; Psychomotor Performance/physiology ; Reading ; *Verbal Behavior ; Vocabulary ; Wechsler Scales ; }, abstract = {Measures of verbal fluency are common additions to neuropsychological evaluations. Due to the literature demonstrating the impact of demographic variables on these measures, corrective norms have recently been published. However, these norms have yet to be cross-validated. This study sought to cross-validate these norms in a racially diverse psychiatric sample. In addition, this study sought to evaluate the utility of Wide Range Achievement Test, 3rd Edition (WRAT3) Reading Recognition and Wechsler Adult Intelligence Scale-Third Edition (WAIS-III) Vocabulary in attenuating the effect of demographic variables on these measures of verbal fluency. Results supported the utility of Gladsjo et al.'s (1999) norms. Further analysis revealed that both WRAT3 Reading Recognition and WAIS-III Vocabulary scores also attenuated the impact of demographic variables on these measures and accounted for more of the variance. Together, these results suggest that, although the demographically corrected norms adequately attenuate the impact of these variables, norms corrected for WRAT3 Reading Recognition or WAIS-III Vocabulary may account for more of the variance and therefore might be more appropriate and universally applicable.}, } @article {pmid15667049, year = {2004}, author = {van Schaik, P and Turnbull, T and van Wersch, A and Drummond, S}, title = {Presence within a mixed reality environment.}, journal = {Cyberpsychology & behavior : the impact of the Internet, multimedia and virtual reality on behavior and society}, volume = {7}, number = {5}, pages = {540-552}, doi = {10.1089/cpb.2004.7.540}, pmid = {15667049}, issn = {1094-9313}, mesh = {Adolescent ; Adult ; Attention ; Awareness ; Depth Perception ; Evaluation Studies as Topic ; Female ; Humans ; Interview, Psychological ; Male ; Middle Aged ; *Models, Psychological ; Motivation ; Problem Solving ; *Social Environment ; Software ; Space Perception ; *User-Computer Interface ; *Video Games ; *Visual Perception ; }, abstract = {Mixed reality environments represent a new approach to creating technology-mediated experiences. However, there is a lack of empirical research investigating users' actual experience. The aim of the current exploratory, non-experimental study was to establish levels of and identify factors associated with presence, within the framework of Schubert et al.'s model of presence. Using questionnaire and interview methods, the experience of the final performance of the Desert Rain mixed reality environment was investigated. Levels of general and spatial presence were relatively high, but levels of involvement and realness were not. Overall, intrinsic motivation, confidence and intention to re-visit Desert Rain were high. However, age was negatively associated with both spatial presence and confidence to play. Furthermore, various problems in navigating the environment were identified. Results are discussed in terms of Schubert's model and other theoretical perspectives. Implications for system design are presented.}, } @article {pmid15657452, year = {2005}, author = {Paleari, FG and Regalia, C and Fincham, F}, title = {Marital quality, forgiveness, empathy, and rumination: a longitudinal analysis.}, journal = {Personality & social psychology bulletin}, volume = {31}, number = {3}, pages = {368-378}, doi = {10.1177/0146167204271597}, pmid = {15657452}, issn = {0146-1672}, mesh = {Adult ; Affect ; *Empathy ; Female ; Follow-Up Studies ; Humans ; *Interpersonal Relations ; Male ; Marriage/*psychology ; *Memory ; Middle Aged ; Personal Satisfaction ; *Social Behavior ; Surveys and Questionnaires ; }, abstract = {McCullough, Rachal, et al.'s (1998) social-psychological framework of forgiveness informed a longitudinal study that examined the extent to which marital forgiveness is determined by social-cognitive (the offended spouse's rumination and emotional empathy) and relationship variables (the quality of the relationship in which the offense took place). In the study, 119 husbands and 124 wives from long- and medium-term marriages in north Italy provided data at two time points separated by a 6-month interval. Structural equation models showed that rumination and empathy independently predicted concurrent marital forgiveness. Forgiveness in turn predicted concurrent marital quality. Finally, reciprocal directions of effect emerged between forgiveness and marital quality over time. These results are discussed in terms of their implications for promoting forgiveness, and future research directions are outlined.}, } @article {pmid15652692, year = {2005}, author = {Hartwig, KA and Eng, E and Daniel, M and Ricketts, T and Quinn, SC}, title = {AIDS and "shared sovereignty" in Tanzania from 1987 to 2000: a case study.}, journal = {Social science & medicine (1982)}, volume = {60}, number = {7}, pages = {1613-1624}, doi = {10.1016/j.socscimed.2004.08.031}, pmid = {15652692}, issn = {0277-9536}, mesh = {Acquired Immunodeficiency Syndrome/economics/epidemiology/*prevention & control ; Communicable Disease Control/economics/methods/*organization & administration ; Developing Countries ; Financing, Organized ; Government Agencies/*organization & administration ; Health Promotion/economics/methods/*organization & administration ; Humans ; International Agencies/*organization & administration ; Interviews as Topic ; Organizational Case Studies ; Tanzania/epidemiology ; World Health Organization ; }, abstract = {After more than 15 years of foreign assistance to support HIV/AIDS prevention in Sub-Saharan Africa, HIV rates in the sub-continent remain high with only a few examples of reduced HIV incidence. This case study used the frame of "shared sovereignty" between nation-states and official development assistance agencies to analyze 13 years of technical assistance for HIV/AIDS programs in Tanzania from 1987 to 2000. The study draws on 21 key informant interviews and a systematic review of key program documents from the National AIDS Control Programme (NACP) and 14 other international agencies. Applying Jamison et al.'s (Lancet 351 (1998) 514) shared sovereignty framework, the analysis focused on fulfilled shared functions in moving Tanzania's NACP from dependence to independence. The analysis revealed an uneven and inconsistent level of technical assistance to the NACP with a rotation of multilateral and bilateral donors over the period of study. The Tanzanian government was often ambivalent toward agencies providing assistance towards its HIV/AIDS programs and toward its own NACP. Results are discussed in terms of implications for future strategic planning to mitigate the effects of HIV/AIDS. Determining roles, shared accountability and responsibility in a shared sovereignty framework remain a challenge in the governance of HIV/AIDS programs in Tanzania.}, } @article {pmid15648493, year = {2004}, author = {Stins, JF and Vosse, S and Boomsma, DI and de Geus, EJ}, title = {On the role of working memory in response interference.}, journal = {Perceptual and motor skills}, volume = {99}, number = {3 Pt 1}, pages = {947-958}, doi = {10.2466/pms.99.3.947-958}, pmid = {15648493}, issn = {0031-5125}, mesh = {Adult ; *Attention ; Humans ; *Memory ; *Photic Stimulation ; Reaction Time ; }, abstract = {A recent study by de Fockert, et al. claimed that working memory and selective attention are interacting cognitive systems. We used a dual task design that closely resembled de Fockert, et al.'s experiment, but using different stimuli. Our subjects first had to store the positions and sequence of a number of blocks. During storage they then had to respond to a few selective attention trials, after which memory was tested. Selective attention was tested using a computerized version of the color Stroop task and the Simon task. We expected to find a monotonic increase of response interference with increasing working memory load, but we found only modest evidence of an influence of working memory on attention. The results shed new light on the nature of and the relation between these cognitive systems.}, } @article {pmid15641908, year = {2005}, author = {Maddox, WT and Ing, AD}, title = {Delayed feedback disrupts the procedural-learning system but not the hypothesis-testing system in perceptual category learning.}, journal = {Journal of experimental psychology. Learning, memory, and cognition}, volume = {31}, number = {1}, pages = {100-107}, doi = {10.1037/0278-7393.31.1.100}, pmid = {15641908}, issn = {0278-7393}, support = {R01 MH59196/MH/NIMH NIH HHS/United States ; }, mesh = {Analysis of Variance ; *Feedback ; Humans ; *Learning ; *Perception ; *Semantics ; }, abstract = {W. T. Maddox, F. G. Ashby, and C. J. Bohil (2003) found that delayed feedback adversely affects information-integration but not rule-based category learning in support of a multiple-systems approach to category learning. However, differences in the number of stimulus dimensions relevant to solving the task and perceptual similarity failed to rule out 2 single-system interpretations. The authors conducted an experiment that remedied these problems and replicated W. T. Maddox et al.'s findings. The experiment revealed a strong performance decrement for information-integration but not rule-based category learning under delayed feedback that was due to an increase in the number of observers using hypothesis-testing strategies to solve the information-integration task, and lower accuracy rates for the few observers using information-integration strategies.}, } @article {pmid15625792, year = {2004}, author = {García-Montes, JM and Pérez-Alvarez, M and Fidalgo, AM}, title = {Influence of metacognitive variables and thought suppression on number of thoughts, discomfort they produce and number and quality of auditory illusions.}, journal = {Cognitive behaviour therapy}, volume = {33}, number = {4}, pages = {181-186}, doi = {10.1080/16506070410029793}, pmid = {15625792}, issn = {1650-6073}, mesh = {Acoustic Stimulation ; Adolescent ; Adult ; *Attention ; Awareness ; Cognitive Behavioral Therapy/*methods ; *Cognitive Dissonance ; Culture ; Female ; Hallucinations/psychology/*therapy ; Humans ; *Internal-External Control ; Male ; Self Concept ; Students/psychology ; Superstitions ; *Thinking ; }, abstract = {Based on the model proposed by Morrison, Haddock & Tarrier (1995) on auditory hallucinations, this study explores the relationships between certain metacognitive variables and number of thoughts, the discomfort they produce, number of auditory illusions and the quality with which they are perceived in a sample from a non-clinical population. After group administration of the Metacognitions Questionnaire, 61 participants were randomly assigned to a suppression group (n = 31) or a focalization group (n = 30) in relation to thoughts with different degrees of self-discrepancy. Forty-eight hours after the set task, a non-vocal auditory stimulus was presented, and subjects were required to say whether they heard any words and, if so, how clearly. The results show how the metacognitive factors studied are useful for predicting our findings only for the suppression group and not for that of focalization. These data are discussed in the light of Morrison et al.'s model of auditory hallucinations.}, } @article {pmid15610476, year = {2004}, author = {Allen, D and Griffiths, L and Lyne, P}, title = {Understanding complex trajectories in health and social care provision.}, journal = {Sociology of health & illness}, volume = {26}, number = {7}, pages = {1008-1030}, doi = {10.1111/j.0141-9889.2004.00426.x}, pmid = {15610476}, issn = {0141-9889}, mesh = {Anthropology, Cultural ; Attitude of Health Personnel ; Continuity of Patient Care/organization & administration ; Humans ; *Interinstitutional Relations ; Needs Assessment ; Nursing Methodology Research ; Patient Care Team/*organization & administration ; Social Work/*organization & administration ; State Medicine/*organization & administration ; *Stroke Rehabilitation ; Surveys and Questionnaires ; Wales ; }, abstract = {Abstract Ensuring collaboration between health and social care providers is a well-established policy concern in most developed countries. Thus far, however, this has proved to be a frustratingly elusive goal. Despite the growing body of empirical work devoted to this issue, social scientific theorising on the management of complex caring trajectories remains under-developed. This paper is an attempt to begin to address this gap in the literature. Drawing on Strauss et al.'s (1985) writings on illness trajectories and Elias's (1978) game model, we offer a framework - centred on the notion of a caring trajectory game - that can assist understanding of the linkages between individual trajectories of care and broader health and social care systems. It is only when we have developed a more theoretically sophisticated understanding of this relationship that we can begin to explain why trajectories of care take the course that they do. The framework arises from our analysis of eight ethnographic case studies of adults undergoing rehabilitation from a first acute stroke. In this paper we illustrate its utility by reference to one specific case: Edward.}, } @article {pmid15609784, year = {2004}, author = {Poulos, C and Bahl, R and Whittington, D and Bhan, MK and Clemens, JD and Acosta, CJ}, title = {A cost-benefit analysis of typhoid fever immunization programmes in an Indian urban slum community.}, journal = {Journal of health, population, and nutrition}, volume = {22}, number = {3}, pages = {311-321}, pmid = {15609784}, issn = {1606-0997}, mesh = {Adolescent ; Adult ; Child ; Child, Preschool ; *Cost of Illness ; Cost-Benefit Analysis ; Female ; Humans ; Immunization Programs/*economics ; India ; Infant ; Infant, Newborn ; Male ; *Poverty Areas ; Treatment Outcome ; Typhoid Fever/economics/*prevention & control ; Typhoid-Paratyphoid Vaccines/*economics ; Urban Health ; }, abstract = {Many economic analyses of immunization programmes focus on the benefits in terms of public-sector cost savings, but do not incorporate estimates of the private cost savings that individuals receive from vaccination. This paper considers the implications of Bahl et al.'s cost-of-illness estimates for typhoid immunization policy by examining how community-level incidence estimates and information on distribution of costs of illness among patients and the public-health sector can be used in the economic analysis of vaccination-programme options. The findings illustrate why typhoid vaccination programmes may often appear to be unattractive to public-health officials who adopt a public budgetary perspective. Under many plausible sets of assumptions, public-sector expenditure on typhoid vaccination does not yield comparable public-sector cost savings. If public-health officials adopt a societal perspective on the economic benefits of vaccination, there are many situations in which different vaccination programmes will make economic sense. The findings show that this is especially true when public decision-makers recognize that (a) the incidence of typhoid fever is underestimated by blood culture-positive cases and (b) avoided costs of illness represent a significant underestimate of the actual economic benefits to individuals of vaccination.}, } @article {pmid15546596, year = {2004}, author = {Volcy, M and Toro, ME and Uribe, CS and Toro, G}, title = {Primary angiitis of the central nervous system: report of five biopsy-confirmed cases from Colombia.}, journal = {Journal of the neurological sciences}, volume = {227}, number = {1}, pages = {85-89}, doi = {10.1016/j.jns.2004.08.007}, pmid = {15546596}, issn = {0022-510X}, mesh = {Adolescent ; Adult ; Biopsy/methods ; Central Nervous System/*pathology ; Colombia/epidemiology ; Female ; Headache/etiology ; Humans ; Lymphocytosis/etiology ; Magnetic Resonance Imaging ; Male ; Retrospective Studies ; Vasculitis, Central Nervous System/cerebrospinal fluid/complications/*pathology ; }, abstract = {INTRODUCTION: Primary (isolated) angiitis of the central nervous system (PACNS) is a rare cause of cerebrovascular disease (CVD), and few leptomeningeal and brain biopsy (LBB)-confirmed cases have been reported from South America.

METHODS: We retrospectively reviewed charts of patients with diagnosis of cerebral angiitis admitted between March 1991 and July 2001 to a single university hospital in Medellin, Colombia. Patients with definitive diagnosis of PACNS by Alrawi et al.'s LBB criteria were selected. We excluded other causes of cerebral angiitis as well as cases without LBB confirmation.

RESULTS: We report five patients, four men and one woman, with a mean age at onset of 24.4 years, and an average disease progression of 12.4 days. Four presented with headache and motor weakness, three had seizures, and two had alterations of consciousness. Cerebral MRI was abnormal in all five cases; brain CT in four, and cerebral angiography in two. The cerebrospinal fluid (CSF) was abnormal in two patients. Leptomeningeal and brain biopsies revealed mononuclear infiltration in the wall of small blood vessels in all. Three had concurrent meningeal and cerebral involvement, two had necrotizing angiitis, and one had vascular and encephalitic lesions. All received only steroid treatment; the 1-year follow-up revealed good prognosis without relapses.

CONCLUSION: We report five biopsy-proven cases of PACNS from Colombia associated with neurological and neuroimaging abnormalities; these patients presented a mild inflammatory disease that was correlated with few CSF abnormalities and good response to single steroid treatment without relapses. Leptomeningeal and brain biopsy is mandatory for a definitive diagnosis.}, } @article {pmid15542236, year = {2004}, author = {Hutzler, F and Bergmann, J and Conrad, M and Kronbichler, M and Stenneken, P and Jacobs, AM}, title = {Inhibitory effects of first syllable-frequency in lexical decision: an event-related potential study.}, journal = {Neuroscience letters}, volume = {372}, number = {3}, pages = {179-184}, doi = {10.1016/j.neulet.2004.07.050}, pmid = {15542236}, issn = {0304-3940}, mesh = {Adult ; Decision Making/*physiology ; Electroencephalography ; Evoked Potentials, Visual/*physiology ; Female ; Frontal Lobe/physiology ; Humans ; Language ; Male ; Reaction Time/physiology ; *Reading ; Regression Analysis ; Visual Perception/*physiology ; }, abstract = {Electrophysiological correlates of the behaviorally well-documented inhibitory effect of first syllable-frequency during lexical access are presented. In a lexical decision task, response times to words with high-frequency first syllables were longer than those to words with low-frequency first syllables and resulted in more negative event-related potentials (ERPs) in an early time window from 190 ms to 280 ms and in the N400 component. The onset of the observed first syllable-frequency effect was prior to the onset of the effect of lexicality (i.e., the first reliable differentiation in ERP waveforms in response to words and pseudowords, a potential marker of lexical access). The present study's results support Barber et al.'s [Neuroreport 15 (2004) 545] notion of the prelexical nature of the first syllable-frequency effect by (A) providing evidence for electrophysiological correlates of first syllable-frequency in another, non-Romance orthography (i.e., German), (B) relating the onset of the first syllable-frequency effect to the onset of the lexicality effect and (C) strengthening this pattern of results by means of a novel item-based analysis of ERP data. Implications of the prelexical nature of the inhibitory first syllable-frequency effect for computational models of reading, specifically for Ans et al.'s [Psychol. Rev. 105 (1998) 678] multiple-trace memory (MTM) model of reading are discussed.}, } @article {pmid15539542, year = {2004}, author = {Minkler, M}, title = {Ethical challenges for the "outside" researcher in community-based participatory research.}, journal = {Health education & behavior : the official publication of the Society for Public Health Education}, volume = {31}, number = {6}, pages = {684-697}, doi = {10.1177/1090198104269566}, pmid = {15539542}, issn = {1090-1981}, mesh = {*Community Participation ; Community-Institutional Relations ; *Cooperative Behavior ; Decision Making/ethics ; *Ethics, Research ; Health Services Research/*ethics ; Humans ; Power, Psychological ; *Prejudice ; Research Personnel/*ethics ; Social Change ; Social Identification ; Social Values ; }, abstract = {Although community-based participatory research (CBPR) shares many of the core values of health education and related fields, the outside researcher embracing this approach to inquiry frequently is confronted with thorny ethical challenges. Following a brief review of the conceptual and historical roots of CBPR, Kelly's ecological principles for community-based research and Jones's three-tiered framework for understanding racism are introduced as useful frameworks for helping explore several key challenges. These are (a) achieving a true "community-driven" agenda; (b) insider-outsider tensions; (c) real and perceived racism; (d) the limitations of "participation"; and (e) issues involving the sharing, ownership, and use of findings for action. Case studies are used in an initial exploration of these topics. Green et al.'s guidelines for appraising CBPR projects then are highlighted as an important tool for helping CBPR partners better address the challenging ethical issues often inherent in this approach.}, } @article {pmid15538611, year = {2005}, author = {Olze, A and Bilang, D and Schmidt, S and Wernecke, KD and Geserick, G and Schmeling, A}, title = {Validation of common classification systems for assessing the mineralization of third molars.}, journal = {International journal of legal medicine}, volume = {119}, number = {1}, pages = {22-26}, pmid = {15538611}, issn = {0937-9827}, mesh = {Adolescent ; Adult ; Age Determination by Teeth/*methods ; Child ; Female ; Forensic Dentistry/methods ; Humans ; Molar, Third/*physiology ; Tooth Calcification/*physiology ; }, abstract = {One major criterion for dental age estimation is the evaluation of third molar mineralization. There are various methods for evaluating tooth mineralization based on classification by stages. The aim of the present work is to assess the validity of the common classification systems. To this end, we analyzed 420 conventional orthopantomograms of German females aged 12-25 years old. The mineralization status of tooth 38 was determined using the stages defined by Gleiser and Hunt, Demirjian et al., Gustafson and Koch, Harris and Nortje and Kullman et al., respectively. Of the methods tested, the most accurate results were obtained with Demirjian et al.'s classification system, which performed best not only for observer agreement but also for the correlation between estimated and true age. It is argued that this is due to the fact that Demirjian et al.'s classification is based on a sufficient number of stages which are defined independently of speculative estimations of length. This leads to the conclusion that the method devised by Demirjian et al. should be used for evaluating the mineralization of third molars for purposes of forensic age determination.}, } @article {pmid15535174, year = {2004}, author = {Yonelinas, AP and Quamme, JR and Widaman, KF and Kroll, NE and Sauvé, MJ and Knight, RT}, title = {Mild hypoxia disrupts recollection, not familiarity.}, journal = {Cognitive, affective & behavioral neuroscience}, volume = {4}, number = {3}, pages = {393-400; discussion 401-406}, pmid = {15535174}, issn = {1530-7026}, mesh = {Brain Damage, Chronic/*physiopathology ; Data Interpretation, Statistical ; Humans ; Hypoxia/*physiopathology ; *Mental Recall ; Models, Psychological ; ROC Curve ; *Recognition, Psychology ; }, abstract = {Yonelinas et al. (2002) found that hypoxic patients exhibited deficits in recollection that left familiarity relatively unaffected. In contrast, Manns, Hopkins, Reed, Kitchener, and Squire (2003) studied a group of hypoxic patients who suffered severe and equivalent deficits in recollection and familiarity. We reexamine those studies and argue that the discrepancy in results is likely due to differences in the hypoxic groups that were tested (i.e., differences in amnestic severity, subject sampling methods, and patient etiology). Yonelinas et al. examined memory in 56 cardiac arrest patients who suffered a brief hypoxic event, whereas Manns et al. examined a group of severely amnesic patients that consisted of 2 cardiac arrest patients, 2 heroin overdose patients, 1 carbon monoxide poisoning patient, and 2 patients with unknown etiologies. We also consider an alternative explanation proposed by Wixted and Squire (2004), who argued that the two patient groups suffered similar deficits, but that statistical or methodological artifacts distorted the results of each of Yonelinas et al.'s experiments. A consideration of those results, however, indicates that such an explanation does not account for the existing data. All of the existing evidence indicates that recollection, but not familiarity, is disrupted in mild hypoxic patients. In more severe cases of hypoxia, or those with more complex etiologies such as heroin overdose, more profound deficits may be observed.}, } @article {pmid15531607, year = {2005}, author = {Sandelin, E}, title = {Extracting multiple structural alignments from pairwise alignments: a comparison of a rigorous and a heuristic approach.}, journal = {Bioinformatics (Oxford, England)}, volume = {21}, number = {7}, pages = {1002-1009}, pmid = {15531607}, issn = {1367-4803}, support = {R01 GM063817/GM/NIGMS NIH HHS/United States ; GM-63817/GM/NIGMS NIH HHS/United States ; }, mesh = {*Algorithms ; Amino Acid Sequence ; Molecular Sequence Data ; Proteins/analysis/*chemistry/*classification ; Sequence Alignment/*methods ; Sequence Analysis, Protein/*methods ; Sequence Homology, Amino Acid ; Software ; }, abstract = {MOTIVATION: Multiple structural alignments (MSTAs) provide position-specific information on the sequence variability allowed by protein folds. This information can be exploited to better understand the evolution of proteins and the physical chemistry of polypeptide folding. Most MSTA methods rely on a pre-computed library of pairwise alignments. This library will in general contain conflicting residue equivalences not all of which can be realized in the final MSTA. Hence to build a consistent MSTA, these methods have to select a conflict-free subset of equivalences.

RESULTS: Using a dataset with 327 families from SCOP 1.63 we compare the ability of two different methods to select an optimal conflict-free subset of equivalences. One is an implementation of Reinert et al.'s integer linear programming formulation (ILP) of the maximum weight trace problem (Reinert et al., 1997, Proc. 1st Ann. Int. Conf. Comput. Mol. Biol. (RECOMB-97), ACM Press, New York). This ILP formulation is a rigorous approach but its complexity is difficult to predict. The other method is T-Coffee (Notredame et al., 2000) which uses a heuristic enhancement of the equivalence weights which allow it to use the speed and simplicity of the progressive alignment approach while still incorporating information of all alignments in each step of building the MSTA. We find that although the ILP formulation consistently selects a more optimal set of conflict-free equivalences, the differences are small and the quality of the resulting MSTAs are essentially the same for both methods. Given its speed and predictable complexity, our results show that T-Coffee is an attractive alternative for producing high-quality MSTAs.}, } @article {pmid15517059, year = {2004}, author = {Figlie, NB and Dunn, J and Laranjeira, R}, title = {[Factor structure of the Stages of Change Readiness and Treatment Eagerness Scale (SOCRATES) in alcohol dependent outpatients].}, journal = {Revista brasileira de psiquiatria (Sao Paulo, Brazil : 1999)}, volume = {26}, number = {2}, pages = {91-99}, doi = {10.1590/s1516-44462004000200005}, pmid = {15517059}, issn = {1516-4446}, mesh = {Alcohol Drinking/*psychology ; Alcoholism/*therapy ; Ambulatory Care ; Attitude to Health ; Humans ; Male ; *Motivation ; Patient Acceptance of Health Care ; Reproducibility of Results ; *Surveys and Questionnaires ; }, abstract = {OBJECTIVE: The aim of this study was to investigate the reliability and factor structure of the Stages of Change Readiness and Treatment Eagerness Scale (SOCRATES), version 8, a 19-item self-reported instrument developed to measure readiness to change in alcohol-dependent alcoholics.

METHODS: A Confirmatory Factor analysis of the SOCRATES was performed based on the factor structures previously demonstrated by Miller & Tonigan and Maisto et al. in a sample with 326 alcohol-dependent outpatients. The questionnaire was translated into Portuguese, cross-culturally adapted and back-translated into English. During this process SOCRATES underwent some modifications to simplify some complex question formats.

RESULTS: The analysis showed that two correlated factors provided the best fit for the data and that these were similar to Maisto et al.'s factors.

CONCLUSIONS: There was less evidence to support a three-factor structure. The results are compared to previous studies and the reasons for discrepancies are discussed.}, } @article {pmid15502998, year = {2004}, author = {Nishio, A and Takami, T and Ohata, K and Hara, M and Mitsuhashi, Y and Yokote, H and Inoue, Y and Hosogai, M and Ichida, T and Ikeda, S}, title = {Three-dimensional rotation venography using the digital subtraction angiography unit with a flat-panel detector: usefulness for the transtemporal/transtentorial approaches.}, journal = {Neuroradiology}, volume = {46}, number = {11}, pages = {876-882}, pmid = {15502998}, issn = {0028-3940}, mesh = {Adult ; Aged ; *Angiography, Digital Subtraction ; Brain Diseases/*diagnostic imaging ; Cerebral Veins/*diagnostic imaging ; Cranial Sinuses/*diagnostic imaging ; Female ; Humans ; Image Processing, Computer-Assisted ; *Imaging, Three-Dimensional ; Male ; Middle Aged ; Phlebography/*instrumentation ; }, abstract = {We obtained the venograms using the two-dimensional digital subtraction angiography (2D DSA) images and three dimensional rotation venography (3D RV) images and investigated the potential usefulness of the 3D RV compared with venograms of 2D DSA using the newly developed three-dimensional rotation angiography unit with a flat-panel detector (FPD). This study included 26 sides (11 left, 15 right) in 20 cases (4 males and 16 females) who underwent radiographic examination for management of intracranial tumors and vascular diseases between May 2003 and December 2003. Each patient underwent diagnostic angiography performed on a DSA unit with a FPD. In all patients, the 2D DSA images, including anteroposterior view and lateral view of the carotid artery, were obtained in two stereoscopic views. The 3D RV was used to produce volume-rendered images. Two neuroradiologists investigated the venous configuration of 3D RV compared with that of 2D DSA about the relationship of the venous drainage system on the temporal lobe according to Guppy et al.'s classification. Twenty-four sides of the 26 sides enabled the precious visualization on 3D RV images. In investigation of 2D DSA, 9 sides (37.5%) were classified into type A, 13 (54.2%) into type B, two (8.3%) into type C, and no sides into types D, E, and F. In investigation of 3D RV images, 10 sides (41.7%) were classified into type A, 9 (37.5%) into type B, 1 (4.2%) into type C, 2 (8.3%) into type E, and 2 (8.3%) into type F. Seven of 24 sides demonstrated discrepancy in results between 2D DSA and 3D RV. The 3D RV could be performed by setting the adequate delay in between the injection of the contrast material and starting time of third rotation to acquire the opacified images. In Guppy et al.'s classification, the 3D RV images could demonstrate the precious venous drainage including the venous lakes with use of multiple views and variable reconstruction compared with 2D DSA. Our DSA system with FPD could provide good 3D RV images. These images are very useful for the skull-base surgery because we can understand the three-dimensional vascular anatomy preoperatively.}, } @article {pmid15491899, year = {2004}, author = {Markman, EM and Abelev, M}, title = {Word learning in dogs?.}, journal = {Trends in cognitive sciences}, volume = {8}, number = {11}, pages = {479-81; discussion 481}, doi = {10.1016/j.tics.2004.09.007}, pmid = {15491899}, issn = {1364-6613}, mesh = {Animals ; Association Learning ; Dogs ; *Learning ; *Verbal Learning ; *Vocabulary ; }, abstract = {In a recent paper, Kaminski, Call and Fischer report pioneering research on word-learning in a dog. In this commentary we suggest ways of distinguishing referential word use from mere association. We question whether the dog is reasoning by exclusion and, if so, compare three explanations - learned heuristics, default assumptions, and pragmatic reasoning - as they apply to children and might apply to dogs. Kaminski et al.'s work clearly raises important questions about the origins and basis of word learning and social cognition.}, } @article {pmid15478760, year = {2004}, author = {Ito, Y and Hatta, T}, title = {Spatial structure of quantitative representation of numbers: evidence from the SNARC effect.}, journal = {Memory & cognition}, volume = {32}, number = {4}, pages = {662-673}, pmid = {15478760}, issn = {0090-502X}, mesh = {Adult ; Female ; Humans ; Male ; Reaction Time ; *Space Perception ; Surveys and Questionnaires ; *Visual Perception ; }, abstract = {Dehaene, Bossini, and Giraux (1993) revealed that subjects responded to large numbers faster with the choice on the right than with the choice on the left, whereas the reverse held true for small numbers (SNARC effect). According to Dehaene et al. (1993), the SNARC effect depends on the quantitative representation of number, such as a left-to-right-oriented analog number line. The main goal of the present study was twofold: first, to investigate whether the vertical SNARC effect could be observed, and, second, to verify whether Dehaene et al.'s (1993) explanation of the SNARC effect is correct. Experiments 2A and 2B showed the vertical SNARC effect in a parity judgment task. Subjects responded to large numbers faster with the top choice than with the bottom choice, whereas the reverse held true for small numbers. However, Experiment 3 failed to show the SNARC effect in a number magnitude judgment task, suggesting that the quantitative representation could be dissociated from the spatial code that produces the SNARC effect.}, } @article {pmid15471031, year = {2004}, author = {Hull, B}, title = {The new dirt on hand hygiene.}, journal = {Kentucky nurse}, volume = {52}, number = {2}, pages = {9}, pmid = {15471031}, issn = {0742-8367}, abstract = {Brown et al.'s (2003) study supported that the use of alcohol-based hand rubs would improve hand hygiene compliance and decrease the incidence of cross-infection. The results of this study can be used to support a group research utilization project that would educate nurses about the use of alcohol-based hand rubs as an effective technique for hand hygiene. Feasibility issues could include cost of the antiseptic and dispensers, placement of dispensers in relation to patient care, and education sessions with the nurses on how and when to use the antiseptic. Future research could be done to examine various nations' compliance with hand hygiene through use of a alcohol-based hand rubs, while also using a more discrete means of observation.}, } @article {pmid15469192, year = {2004}, author = {Hochman, KM and Lewine, RR}, title = {Age of menarche and schizophrenia onset in women.}, journal = {Schizophrenia research}, volume = {69}, number = {2-3}, pages = {183-188}, doi = {10.1016/s0920-9964(03)00176-2}, pmid = {15469192}, issn = {0920-9964}, support = {MH44151/MH/NIMH NIH HHS/United States ; }, mesh = {Adult ; Age Factors ; Age of Onset ; Aged ; Aged, 80 and over ; Aging/physiology ; Behavioral Symptoms ; Female ; Humans ; Menarche/*physiology ; Middle Aged ; Schizophrenia/*epidemiology/*physiopathology ; }, abstract = {OBJECTIVE: The "estrogen hypothesis" posits that this hormone serves as a protective factor in the development of schizophrenia. If true, then it is expected that the earlier the age of menarche, the later the onset of schizophrenia (as has been reported by some investigators). This study attempts to replicate this relationship in a sample of women with schizophrenia and schizoaffective disorder.

METHOD: Self-report menarche age, clinical status, and onset of disorder were collected in a sample of 68 women (55 diagnosed with schizophrenia and 13 with schizoaffective disorder).

RESULTS: Menarche age and schizophrenia onset were not negatively correlated as would be predicted by the estrogen hypothesis. Two clinical measures, however, did correlate with age of menarche as predicted. Higher negative symptom scores (total SANS) and greater functional impairment (lower GAF) were reported in subjects who reported a later age at menarche.

CONCLUSION: This study suggests that an earlier age at menarche might predict improved clinical outcome after schizophrenia onset (in support of the estrogen hypothesis). Our data, however, do not support Cohen et al.'s findings regarding the relationship between age at menarche, and the timing of the onset of the disorder. Further investigations regarding the relationship between estrogen and schizophrenia development in women are needed. It is suggested that other developmental factors, both biological and psychosocial, might play a crucial role in both the age at onset and the outcome of the disorder in women.}, } @article {pmid15446421, year = {2004}, author = {Ricklefs, RE and Bermingham, E}, title = {Application of Johnson et al.'s speciation threshold model to apparent colonization times of island biotas.}, journal = {Evolution; international journal of organic evolution}, volume = {58}, number = {8}, pages = {1664-1673}, doi = {10.1111/j.0014-3820.2004.tb00452.x}, pmid = {15446421}, issn = {0014-3820}, mesh = {Animals ; *Biodiversity ; Birds/*genetics ; Computer Simulation ; *Genetic Variation ; *Genetics, Population ; Geography ; Hawaii ; *Models, Biological ; *Phylogeny ; Population Dynamics ; Species Specificity ; West Indies ; }, abstract = {Understanding patterns of diversity can be furthered by analysis of the dynamics of colonization, speciation, and extinction on islands using historical information provided by molecular phylogeography. The land birds of the Lesser Antilles are one of the most thoroughly described regional faunas in this context. In an analysis of colonization times, Ricklefs and Bermingham (2001) found that the cumulative distribution of lineages with respect to increasing time since colonization exhibits a striking change in slope at a genetic distance of about 2% mitochondrial DNA sequence divergence (about one million years). They further showed how this heterogeneity could be explained by either an abrupt increase in colonization rates or a mass extinction event. Cherry et al. (2002), referring to a model developed by Johnson et al. (2000), argued instead that the pattern resulted from a speciation threshold for reproductive isolation of island populations from their continental source populations. Prior to this threshold, genetic divergence is slowed by migration from the source, and species of varying age accumulate at a low genetic distance. After the threshold is reached, source and island populations diverge more rapidly, creating heterogeneity in the distribution of apparent ages of island taxa. We simulated of Johnson et al.'s speciation-threshold model, incorporating genetic divergence at rate k and fixation at rate M of genes that have migrated between the source and the island population. Fixation resets the divergence clock to zero. The speciation-threshold model fits the distribution of divergence times of Lesser Antillean birds well with biologically plausible parameter estimates. Application of the model to the Hawaiian avifauna, which does not exhibit marked heterogeneity of genetic divergence, and the West Indian herpetofauna, which does, required unreasonably high migration-fixation rates, several orders of magnitude greater than the colonization rate. However, the plausibility of the speciation-divergence model for Lesser Antillean birds emphasizes the importance of further investigation of historical biogeography on a regional scale for whole biotas, as well as the migration of genes between populations on long time scales and the achievement of reproductive isolation.}, } @article {pmid15376813, year = {2004}, author = {Speckman, PL and Rouder, JN}, title = {A comment on Heathcote, Brown, and Mewhort's QMLE method for response time distributions.}, journal = {Psychonomic bulletin & review}, volume = {11}, number = {3}, pages = {574-6; discussion 577-8}, pmid = {15376813}, issn = {1069-9384}, mesh = {Humans ; *Models, Statistical ; *Reaction Time ; }, abstract = {Heathcote, Brown, and Mewhort (2002) have introduced a new, robust method of estimating response time distributions. Their method may have practical advantages over conventional maximum likelihood estimation. The basic idea is that the likelihood of parameters is maximized given a few quantiles from the data. We show that Heathcote et al.'s likelihood function is not correct and provide the appropriate correction. However, although our correction stands on firmer theoretical ground than Heathcote et al.'s, it appears to yield worse parameter estimates. This result further indicates that, at least for some distributions and situations, quantile maximum likelihood estimation may have better nonasymptotic properties than a more theoretically justified approach.}, } @article {pmid15374869, year = {2005}, author = {Chen, TM and Lu, CC and Li, WH}, title = {Prediction of splice sites with dependency graphs and their expanded bayesian networks.}, journal = {Bioinformatics (Oxford, England)}, volume = {21}, number = {4}, pages = {471-482}, doi = {10.1093/bioinformatics/bti025}, pmid = {15374869}, issn = {1367-4803}, mesh = {Bayes Theorem ; Gene Expression Profiling/*methods ; *Models, Genetic ; Models, Statistical ; RNA Splicing/*genetics ; Sequence Alignment/*methods ; Sequence Analysis, DNA/*methods ; }, abstract = {MOTIVATION: Owing to the complete sequencing of human and many other genomes, huge amounts of DNA sequence data have been accumulated. In bioinformatics, an important issue is how to predict the complete structure of genes from the genomic DNA sequence, especially the human genome. A crucial part in the gene structure prediction is to determine the precise exon-intron boundaries, i.e. the splice sites, in the coding region.

RESULTS: We have developed a dependency graph model to fully capture the intrinsic interdependency between base positions in a splice site. The establishment of dependency between two position is based on a chi2-test from known sample data. To facilitate statistical inference, we have expanded the dependency graph (which is usually a graph with cycles that make probabilistic reasoning very difficult, if not impossible) into a Bayesian network (which is a directed acyclic graph that facilitates statistical reasoning). When compared with the existing models such as weight matrix model, weight array model, maximal dependence decomposition, Cai et al.'s tree model as well as the less-studied second-order and third-order Markov chain models, the expanded Bayesian networks from our dependency graph models perform the best in nearly all the cases studied.

AVAILABILITY: Software (a program called DGSplicer) and datasets used are available at http://csrl.ee.nthu.edu.tw/bioinf/

CONTACT: cclu@ee.nthu.edu.tw.}, } @article {pmid15367076, year = {2004}, author = {Bandura, A and Bussey, K}, title = {On broadening the cognitive, motivational, and sociostructural scope of theorizing about gender development and functioning: comment on Martin, Ruble, and Szkrybalo (2002).}, journal = {Psychological bulletin}, volume = {130}, number = {5}, pages = {691-701}, doi = {10.1037/0033-2909.130.5.691}, pmid = {15367076}, issn = {0033-2909}, mesh = {*Cognition ; Female ; Gender Identity ; Humans ; Male ; *Motivation ; *Psychological Theory ; *Psychosexual Development ; Self Concept ; }, abstract = {In their article on gender development, C. L. Martin, D. N. Ruble, and J. Szkrybalo (see record 2002-18663-003) contrasted their conception of gender development with that of social cognitive theory. The authors of this commentary correct misrepresentations of social cognitive theory and analyze the conceptual and empirical status of Martin et al.'s (2002) theory that gender stereotype matching is the main motivating force of gender development. Martin et al. (2002) based their claim for the causal primacy of gender self-categorization on construal of gender discrimination as rudimentary self-identity, equivocal empirical evidence, and dismissal of discordant evidence because of methodological deficiencies. The repeated finding that gendered preferences and behavior precede emergence of a sense of self is discordant with their theory. Different lines of evidence confirm that gender development and functioning are socially situated, richly contextualized, and conditionally manifested rather than governed mainly by an intrinsic drive to match stereotypic gender self-conception.}, } @article {pmid15362394, year = {2004}, author = {Abdel-Khalek, AM}, title = {Death anxiety, death depression, and death obsession: a general factor of death distress is evident: a reply.}, journal = {Psychological reports}, volume = {94}, number = {3 Pt 2}, pages = {1212-1214}, doi = {10.2466/pr0.94.3c.1212-1214}, pmid = {15362394}, issn = {0033-2941}, mesh = {Adolescent ; Adult ; Anxiety/*psychology ; *Attitude to Death ; Cross-Cultural Comparison ; Depression/*psychology ; Egypt ; Factor Analysis, Statistical ; *Fear ; Female ; Humans ; Kuwait ; Male ; Obsessive Behavior/*psychology ; Personality Inventory/statistics & numerical data ; Psychometrics/statistics & numerical data ; Reproducibility of Results ; Students/psychology ; United States ; }, abstract = {A sample of 75 (16 men, and 59 women) Kuwaiti college students responded to Templer's and Collett-Lester Death Anxiety Scales, Templer, et al.'s Death Depression Scale and Abdel-Khalek's Death Obsession Scale. A general high-loaded factor of death distress was extracted using the total scores. However, in using the Collett-Lester four subscales, the Fear of Death and Dying of Others loaded on a second factor.}, } @article {pmid15355130, year = {2004}, author = {Jahn, G}, title = {Three turtles in danger: spontaneous construction of causally relevant spatial situation models.}, journal = {Journal of experimental psychology. Learning, memory, and cognition}, volume = {30}, number = {5}, pages = {969-987}, doi = {10.1037/0278-7393.30.5.969}, pmid = {15355130}, issn = {0278-7393}, mesh = {Acoustic Stimulation ; Discrimination, Psychological ; Humans ; *Judgment ; *Linguistics ; Photic Stimulation ; Recognition, Psychology ; Space Perception/*physiology ; }, abstract = {In 4 experiments, the author explored the spontaneous construction of spatial situation models during discourse comprehension by using the sentence-recognition paradigm of J. D. Bransford, J. R. Barclay, and J. J. Franks (1972). In Experiment 1, signaling causal relevance of spatial relations was a necessary precondition for replicating their original finding of spontaneously constructed spatial representations. Causal relevance was ensured in the subsequent experiments by a judgment task indirectly demanding the evaluation of described spatial relations with regard to causal relevance. Participants spontaneously constructed spatial situation models of text presented auditorily or visually. Effects of spontaneous construction were more reliable when encoding was easier. The results suggest a revised interpretation of J. D. Bransford et al.'s study and corroborate recent evidence showing that relevant spatial information in texts is reliably represented.}, } @article {pmid15327980, year = {2004}, author = {Breitling, R and Armengaud, P and Amtmann, A and Herzyk, P}, title = {Rank products: a simple, yet powerful, new method to detect differentially regulated genes in replicated microarray experiments.}, journal = {FEBS letters}, volume = {573}, number = {1-3}, pages = {83-92}, doi = {10.1016/j.febslet.2004.07.055}, pmid = {15327980}, issn = {0014-5793}, support = {P17237/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Acute Disease ; Algorithms ; Animals ; Arabidopsis/drug effects/genetics ; Gene Expression Profiling/*methods ; Gene Expression Regulation/*genetics ; Genes/genetics ; Humans ; Leukemia/genetics ; Lipoproteins, HDL/deficiency ; Mice ; Models, Animal ; Oligonucleotide Array Sequence Analysis/*methods ; Potassium/pharmacology ; RNA, Messenger/analysis/genetics ; Reproducibility of Results ; Research Design ; }, abstract = {One of the main objectives in the analysis of microarray experiments is the identification of genes that are differentially expressed under two experimental conditions. This task is complicated by the noisiness of the data and the large number of genes that are examined simultaneously. Here, we present a novel technique for identifying differentially expressed genes that does not originate from a sophisticated statistical model but rather from an analysis of biological reasoning. The new technique, which is based on calculating rank products (RP) from replicate experiments, is fast and simple. At the same time, it provides a straightforward and statistically stringent way to determine the significance level for each gene and allows for the flexible control of the false-detection rate and familywise error rate in the multiple testing situation of a microarray experiment. We use the RP technique on three biological data sets and show that in each case it performs more reliably and consistently than the non-parametric t-test variant implemented in Tusher et al.'s significance analysis of microarrays (SAM). We also show that the RP results are reliable in highly noisy data. An analysis of the physiological function of the identified genes indicates that the RP approach is powerful for identifying biologically relevant expression changes. In addition, using RP can lead to a sharp reduction in the number of replicate experiments needed to obtain reproducible results.}, } @article {pmid15325352, year = {2004}, author = {Hayasaka, S and Nichols, TE}, title = {Combining voxel intensity and cluster extent with permutation test framework.}, journal = {NeuroImage}, volume = {23}, number = {1}, pages = {54-63}, doi = {10.1016/j.neuroimage.2004.04.035}, pmid = {15325352}, issn = {1053-8119}, mesh = {Artifacts ; Brain/pathology/*physiopathology ; Brain Mapping ; Cerebral Cortex/pathology/physiopathology ; Cluster Analysis ; Computer Simulation ; Emotions/physiology ; Humans ; Image Processing, Computer-Assisted/*statistics & numerical data ; *Linear Models ; Magnetic Resonance Imaging/*statistics & numerical data ; *Mathematical Computing ; Memory, Short-Term/physiology ; Sensitivity and Specificity ; }, abstract = {In a massively univariate analysis of brain image data, statistical inference is typically based on intensity or spatial extent of signals. Voxel intensity-based tests provide great sensitivity for high intensity signals, whereas cluster extent-based tests are sensitive to spatially extended signals. To benefit from the strength of both, the intensity and extent information needs to be combined. Various ways of combining voxel intensity and cluster extent are possible, and a few such combining methods have been proposed. Poline et al.'s [NeuroImage 16 (1997) 83] minimum P value approach is sensitive to signals whose either intensity or extent is significant. Bullmore et al.'s [IEEE Trans. Med. Imag. 18 (1999) 32] cluster mass method can detect signals whose intensity and extent are sufficiently large, even when they are not significant by intensity or extent alone. In this work, we study such combined inference methods using combining functions (Pesarin, F., 2001. Multivariate Permutation Tests. Wiley, New York) and permutation framework [Holmes et al., J. Cereb. Blood Flow Metab. 16 (1996) 7], which allow us to examine different ways of combining voxel intensity and cluster extent information without knowing their distribution. We also attempt to calibrate combined inference by using weighted combining functions, which adjust the test according to signals of interest. Furthermore, we propose meta-combining, a combining function of combining functions, which integrates strengths of multiple combining functions into a single statistic. We found that combined tests are able to detect signals that are not detected by voxel or cluster size test alone. We also found that the weighted combining functions can calibrate the combined test according to the signals of interest, emphasizing either intensity or extent as appropriate. Though not necessarily more sensitive than individual combining functions, the meta-combining function is sensitive to all types of signals and thus can be used as a single test summarizing all the combining functions.}, } @article {pmid15298794, year = {2004}, author = {He, X and Fan, S and Zhou, K and Chen, L}, title = {Cue validity and object-based attention.}, journal = {Journal of cognitive neuroscience}, volume = {16}, number = {6}, pages = {1085-1097}, doi = {10.1162/0898929041502689}, pmid = {15298794}, issn = {0898-929X}, mesh = {Adolescent ; Adult ; Analysis of Variance ; Attention/*physiology ; Brain Mapping ; *Cues ; Evoked Potentials/physiology ; Female ; Humans ; Male ; Motion Perception/*physiology ; Orientation/*physiology ; Psychomotor Performance/physiology ; Reaction Time/physiology ; Signal Detection, Psychological ; Space Perception/*physiology ; Time Factors ; }, abstract = {In a previous study, Egly, Driver, and Rafal (1994) observed both space- and object-based components of visual selective attention. However, the mechanisms underlying these two components and the relationship between them are not well understood. In the present research, with a similar paradigm, these issues were addressed by manipulating cue validity. Behavioral results indicated the presence of both space- and object-based components under high cue validity, similar to the results of Egly et al.'s study. In addition, under low cue validity, the space-based component was absent, whereas the object-based component was maintained. Further event-related potential results demonstrated an object-based effect at a sensory level over the posterior areas of brain, and a space-based effect over the anterior region. The present data suggest that the space- and object-based components reflect mainly voluntary and reflexive mechanisms, respectively.}, } @article {pmid15278940, year = {2004}, author = {Bräuer, G and Collard, M and Stringer, C}, title = {On the reliability of recent tests of the Out of Africa hypothesis for modern human origins.}, journal = {The anatomical record. Part A, Discoveries in molecular, cellular, and evolutionary biology}, volume = {279}, number = {2}, pages = {701-707}, doi = {10.1002/ar.a.20064}, pmid = {15278940}, issn = {1552-4884}, mesh = {Africa ; Animals ; *Anthropology, Physical ; Asia ; Australia ; *Biological Evolution ; *Emigration and Immigration ; Hominidae ; Humans ; *Models, Theoretical ; *Phylogeny ; Racial Groups/*genetics ; }, abstract = {In this paper we critique two recent studies that have been claimed to disprove the Out of Africa hypothesis for modern human origins (Hawks et al., 2000; Wolpoff et al., 2001). We show that the test prediction employed by Hawks et al. (2000) and Wolpff et al. (2001) is not relevant to many versions of the Out of Africa hypothesis, and that the key specimens they used are problematic in terms of morphological representativeness. We also show that there are significant problems with the character state datasets employed in the studies. Lastly, we highlight evidence that the main method used in the studies (pairwise difference analysis) is not reliable when applied to the type of data employed by Hawks et al. (2000) and Wolpoff et al. (2001). In view of the foregoing, we contend that Hawks et al.'s (2000) and Wolpoff et al.'s (2001) claim to have disproved the Out of Africa hypothesis cannot be sustained.}, } @article {pmid15271617, year = {2004}, author = {Harwood, MD and Eyberg, SM}, title = {Therapist verbal behavior early in treatment: relation to successful completion of parent-child interaction therapy.}, journal = {Journal of clinical child and adolescent psychology : the official journal for the Society of Clinical Child and Adolescent Psychology, American Psychological Association, Division 53}, volume = {33}, number = {3}, pages = {601-612}, doi = {10.1207/s15374424jccp3303_17}, pmid = {15271617}, issn = {1537-4416}, support = {R01 MH60632/MH/NIMH NIH HHS/United States ; }, mesh = {Adult ; Attention Deficit and Disruptive Behavior Disorders/psychology/*therapy ; Child ; Child, Preschool ; *Communication ; Female ; Humans ; Male ; *Mother-Child Relations ; Patient Dropouts ; *Professional-Patient Relations ; Treatment Outcome ; }, abstract = {We examined the role of specific therapist verbal behaviors in predicting successful completion of Parent-Child Interaction Therapy (PCIT) in 22 families, including 11 families that successfully completed treatment and 11 that discontinued treatment prematurely. The children were 3 to 6 years old and diagnosed with oppositional defiant disorder (ODD). Chamberlain et al.'s (1986) Therapy Process Code (TPC) was used to measure therapist verbalizations during therapist-parent interactions during the initial clinical interview and the second treatment session. Results indicated that therapists' use of the categories Question, Facilitate, and Support during these sessions accurately predicted treatment dropout versus completion for 73% of families. Findings suggest that the early therapist-parent relationship in PCIT may be critical to successful treatment completion.}, } @article {pmid15265147, year = {2004}, author = {Jowett, S and Ntoumanis, N}, title = {The Coach-Athlete Relationship Questionnaire (CART-Q): development and initial validation.}, journal = {Scandinavian journal of medicine & science in sports}, volume = {14}, number = {4}, pages = {245-257}, doi = {10.1111/j.1600-0838.2003.00338.x}, pmid = {15265147}, issn = {0905-7188}, mesh = {Factor Analysis, Statistical ; Female ; Humans ; *Interpersonal Relations ; Male ; Models, Statistical ; Psychometrics ; Reproducibility of Results ; Sports/*psychology ; *Surveys and Questionnaires ; United Kingdom ; }, abstract = {The purpose of the present study was to develop and validate a self-report instrument that measures the nature of the coach-athlete relationship. Jowett et al.'s (Jowett & Meek, 2000; Jowett, in press) qualitative case studies and relevant literature were used to generate items for an instrument that measures affective, cognitive, and behavioral aspects of the coach-athlete relationship. Two studies were carried out in an attempt to assess content, predictive, and construct validity, as well as internal consistency, of the Coach-Athlete Relationship Questionnaire (CART-Q), using two independent British samples. Principal component analysis and confirmatory factor analysis were used to reduce the number of items, identify principal components, and confirm the latent structure of the CART-Q. Results supported the multidimensional nature of the coach-athlete relationship. The latent structure of the CART-Q was underlined by the latent variables of coaches' and athletes' Closeness (emotions), Commitment (cognitions), and Complementarity (behaviors).}, } @article {pmid15264979, year = {2004}, author = {Hall, S and Weinman, J and Marteau, TM}, title = {The motivating impact of informing women smokers of a link between smoking and cervical cancer: the role of coherence.}, journal = {Health psychology : official journal of the Division of Health Psychology, American Psychological Association}, volume = {23}, number = {4}, pages = {419-424}, doi = {10.1037/0278-6133.23.4.419}, pmid = {15264979}, issn = {0278-6133}, mesh = {Adult ; *Attitude to Health ; Female ; Health Behavior ; *Health Education ; Humans ; Intention ; Middle Aged ; *Motivation ; Smoking/*epidemiology ; Smoking Cessation ; Uterine Cervical Neoplasms/*epidemiology ; }, abstract = {This research assessed the role of having a coherent explanation of the link between smoking and cervical cancer in motivating women to stop smoking. In the 1st study, women were given a leaflet with either a detailed or a minimal explanation of the link or no leaflet. The leaflets were similarly effective at providing a coherent explanation. In a cross-sectional analysis, having a coherent explanation moderated the relationship between perceived vulnerability and intention: Higher perceived vulnerability to cervical cancer was associated with greater intention to quit smoking only amongst women with a more coherent explanation of the link between smoking and cervical cancer. This finding was replicated in a 2nd study. These results are consistent with H. Leventhal et al.'s (1997) self-regulatory model, which suggests that motivation to change behavior depends not only on perceiving a threat but also on having a coherent model linking the behavior with the threat.}, } @article {pmid15253095, year = {2004}, author = {Hackmann, A and Ehlers, A and Speckens, A and Clark, DM}, title = {Characteristics and content of intrusive memories in PTSD and their changes with treatment.}, journal = {Journal of traumatic stress}, volume = {17}, number = {3}, pages = {231-240}, doi = {10.1023/B:JOTS.0000029266.88369.fd}, pmid = {15253095}, issn = {0894-9867}, support = {069777//Wellcome Trust/United Kingdom ; }, mesh = {Adult ; Cognitive Behavioral Therapy ; Emotions ; Female ; Humans ; Male ; *Memory ; Middle Aged ; Stress Disorders, Post-Traumatic/*psychology/*therapy ; Wounds and Injuries/*psychology ; }, abstract = {Although intrusive reexperiencing is a core symptom of postraumatic stress disorder (PTSD), relatively little is known about its phenomenology. The present study assessed the characteristics and content of intrusive trauma memories in 22 patients with PTSD, and followed their changes in the course of cognitive behavioral treatment. Patients had a small number of different intrusive memories (1-4, M = 2.2) that occurred in an invariable, repetitive way. The intrusions were distressing and had a vivid perceptual content. They appeared to the patient to be happening in the "here and now." With therapy, the frequency, vividness, distress, and nowness of the intrusions faded gradually. There was no exacerbation with imaginal reliving. The content of intrusions was classified by raters to test A. Ehlers et al.'s (2002) hypothesis that intrusive memories are usually of warning stimuli that signalled the moments with the greatest emotional impact. The results were consistent with this hypothesis.}, } @article {pmid15250752, year = {2004}, author = {Orrick, JJ and Segal, R and Johns, TE and Russell, W and Wang, F and Yin, DD}, title = {Resource use and cost of care for patients hospitalised with community acquired pneumonia: impact of adherence to infectious diseases society of america guidelines.}, journal = {PharmacoEconomics}, volume = {22}, number = {11}, pages = {751-757}, pmid = {15250752}, issn = {1170-7690}, mesh = {Adult ; Anti-Bacterial Agents/*economics/therapeutic use ; Community-Acquired Infections/classification/drug therapy/*economics ; *Cost of Illness ; Female ; Florida ; Health Care Costs/*statistics & numerical data ; Hospitalization/*economics ; Humans ; Length of Stay ; Male ; Middle Aged ; Pneumonia, Bacterial/classification/drug therapy/*economics ; Severity of Illness Index ; }, abstract = {OBJECTIVE: The objective of this study was to compare the inpatient resource use and cost of care for patients hospitalised with community-acquired pneumonia (CAP) who were treated with preferred antibacterial therapy according to the 1998 Infectious Diseases Society of America (IDSA) guidelines with those who were not treated with preferred therapy.

METHODS: A multicentre, observational study was conducted in Florida between 1999 and 2000. Hospitalised adult patients (aged > or = 18 years) started on antibacterial therapy for suspected or confirmed CAP were enrolled in the study. Data collected included patient demographic characteristics, pneumonia risk class, resource use (pharmacy, laboratory, radiology, respiratory services, hospital room and board) and economic data. Risk classification according to Fine et al.'s criteria was determined for each patient. Patient's antibacterial therapy was classified as being preferred or non-preferred according to the 1998 IDSA guidelines. Resource utilisation and cost of care were compared between these two groups.

RESULTS: Ninety-nine patients were enrolled in the study. The average age was 60.6 years +/- 20.5 years. The percentage of patients in each risk class (according to Fine et al.) were 11.1% in class I, 39.4% in class II, 29.3% in class III, 16.2% in class IV and 4% in class V. The mean cost of hospitalisation per admission (excluding physician cost) was US 3,490 dollars +/- US 3,058 dollars (median US 2,430 dollars) with hospital room/board accounting for the largest percentage (83.7%), followed by laboratory (8.1%), antibacterial (4.6%), radiology (2.6%) and respiratory (0.9%) cost centres [year 2000 values]. The majority of patients (75.8%) received preferred antibacterials according to the IDSA guidelines. The group treated with preferred antibacterials had a shorter mean length of hospital stay (4.5 vs 6.8 days, p = 0.002), a lower total cost of hospitalisation (mean US 3,009 dollars +/- US 2,682 dollars vs US 4,992 dollars +/- US 3,686 dollars; median US 2,047 dollars vs US 3,805 dollars, p = 0.021) and lower antibacterial costs (mean US 117 dollars +/- US 79 dollars vs US 301 dollars +/- US 409 dollars; median US 97 dollars vs US 171 dollars, p = 0.038) compared with patients who did not receive preferred therapy.

CONCLUSION: Implementation of protocols according to IDSA guidelines may result in cost savings to institutions wishing to reduce the economic burden associated with treating hospitalised patients for CAP.}, } @article {pmid15249260, year = {2004}, author = {Gallo, LC and Bogart, LM and Vranceanu, AM and Walt, LC}, title = {Job characteristics, occupational status, and ambulatory cardiovascular activity in women.}, journal = {Annals of behavioral medicine : a publication of the Society of Behavioral Medicine}, volume = {28}, number = {1}, pages = {62-73}, doi = {10.1207/s15324796abm2801_8}, pmid = {15249260}, issn = {0883-6612}, support = {MH66101-01/MH/NIMH NIH HHS/United States ; }, mesh = {Adult ; *Blood Pressure ; Cardiovascular Diseases/etiology/pathology ; Female ; *Heart Rate ; Humans ; Internal-External Control ; *Job Description ; Middle Aged ; Morbidity ; *Occupations ; Risk Assessment ; Social Support ; Stress, Psychological/*complications ; }, abstract = {BACKGROUND: Prior research concerning the effects of occupational status and work stress on ambulatory blood pressure (AmBP) has seldom included women, and available results are equivocal. Moreover, the concurrent effects of occupational status and job characteristics have rarely been investigated. Some research is consistent with the idea that stressful job characteristics are especially detrimental to health in low-status workers, creating a cumulative physiological burden.

PURPOSE: To examine the independent and joint effects of occupational status and perceived demands, control, and social support at work on AmBP and heart rate (HR) in women.

METHODS: One hundred eight women (M age = 41.07 years) wore an AmBP monitor for 2 days and completed a self-report assessment of job control, demands, and support (i.e., Karesek et al.'s Job Content Questionnaire).

RESULTS: After controlling for numerous potential confounds, occupational status and job characteristics accounted for 18% and 22% of the inter-individual variability in ambulatory systolic blood pressure (SBP) and HR, respectively. Occupational status independently predicted ambulatory cardiovascular activity and interacted with job characteristics, particularly in relation to SBP.

CONCLUSIONS: Inasmuch as ambulatory SBP and HR predict future cardiovascular morbidity and mortality, women with both lower status occupations and stressful job circumstances could be at disproportionately high cardiovascular risk.}, } @article {pmid15238000, year = {2004}, author = {Asher, SA and Mikhonin, AV and Bykov, S}, title = {UV Raman demonstrates that alpha-helical polyalanine peptides melt to polyproline II conformations.}, journal = {Journal of the American Chemical Society}, volume = {126}, number = {27}, pages = {8433-8440}, doi = {10.1021/ja049518j}, pmid = {15238000}, issn = {0002-7863}, support = {8R01 EB002053021/EB/NIBIB NIH HHS/United States ; }, mesh = {Amides/chemistry ; Chemical Phenomena ; Chemistry, Physical ; Peptides/*chemistry ; Protein Conformation ; Protein Structure, Secondary ; Spectrophotometry, Ultraviolet ; Spectrum Analysis, Raman/*methods ; Temperature ; }, abstract = {We examined the 204-nm UV Raman spectra of the peptide XAO, which was previously found by Shi et al.'s NMR study to occur in aqueous solution in a polyproline II (PPII) conformation. The UV Raman spectra of XAO are essentially identical to the spectra of small peptides such as ala(5) and to the large 21-residue predominantly Ala peptide, AP. We conclude that the non-alpha-helical conformations of these peptides are dominantly PPII. Thus, AP, which is highly alpha-helical at room temperature, melts to a PPII conformation. There is no indication of any population of intermediate disordered conformations. We continued our development of methods to relate the Ramachandran Psi-angle to the amide III band frequency. We describe a new method to estimate the Ramachandran Psi-angular distributions from amide III band line shapes measured in 204-nm UV Raman spectra. We used this method to compare the Psi-distributions in XAO, ala(5), the non-alpha-helical state of AP, and acid-denatured apomyoglobin. In addition, we estimated the Psi-angle distributions of peptide bonds which occur in non-alpha-helix and non-beta-sheet conformations in a small library of proteins.}, } @article {pmid15222846, year = {2004}, author = {Babcock, JC and Green, CE and Webb, SA and Graham, KH}, title = {A second failure to replicate the Gottman et al. (1995) typology of men who abuse intimate partners...and possible reasons why.}, journal = {Journal of family psychology : JFP : journal of the Division of Family Psychology of the American Psychological Association (Division 43)}, volume = {18}, number = {2}, pages = {396-400}, doi = {10.1037/0893-3200.18.2.396}, pmid = {15222846}, issn = {0893-3200}, mesh = {Adult ; Aggression/*physiology/psychology ; Analysis of Variance ; Battered Women ; Female ; Heart Rate/*physiology ; Humans ; *Interpersonal Relations ; Interviews as Topic ; Male ; Middle Aged ; Psychophysiology ; Spouse Abuse/*classification/psychology ; Texas ; }, abstract = {The present study attempts to replicate Gottman et al.'s (1995; see record 1995-44075-001; and Jacobson & Gottman, 1998) psychophysiological study that classifies partner assaultive men into two distinct groups: heart rate (HR) decelerators (Type 1 batterers) and HR accelerators (Type 2 batterers). Current results indicate no significant differences between Type 1 and Type 2 batterers on the antisocial spectrum of behaviors. Resting HR, rather than HR change, was negatively related to the antisocial spectrum of behavior for batterers with severe, clinical levels of violence only. Reasons for subsequent failures to replicate the Type 1 versus Type 2 distinctions may be attributable to unusually high autonomic arousal during baseline in the original study. Consideration of resting HR and the use of dimensional as opposed to categorical approaches in analyzing the heterogeneity of batterers are proposed as possible solutions to clarifying inconsistencies across laboratories.}, } @article {pmid15210378, year = {2004}, author = {Parker, HA and McNally, RJ and Nakayama, K and Wilhelm, S}, title = {No disgust recognition deficit in obsessive-compulsive disorder.}, journal = {Journal of behavior therapy and experimental psychiatry}, volume = {35}, number = {2}, pages = {183-192}, doi = {10.1016/j.jbtep.2004.04.008}, pmid = {15210378}, issn = {0005-7916}, mesh = {Adult ; *Affect ; Basal Ganglia/physiopathology ; Diagnostic and Statistical Manual of Mental Disorders ; *Facial Expression ; Female ; Humans ; Male ; Obsessive-Compulsive Disorder/diagnosis/*physiopathology/psychology ; *Recognition, Psychology ; }, abstract = {BACKGROUND: Patients with basal ganglia abnormalities misclassify facial expressions of disgust as expressions of anger when asked to identify the emotion depicted in photographs of individuals displaying different emotions. Sprengelmeyer, Young, Pundt et al. (1997) reported a similar disgust recognition deficit in patients with obsessive-compulsive disorder (OCD)--an anxiety disorder associated with basal ganglia abnormality.

METHODS: In the present experiment, we attempted to replicate Sprengelmeyer, Young, Pundt et al.'s (1997) findings.

RESULTS: We failed to replicate Sprengelmeyer, Young, Pundt et al.'s finding of disgust recognition deficits in OCD patients relative to healthy control subjects. One patient with especially severe OCD did, however, exhibit impairment by misclassifying disgust expressions as anger expressions.

DISCUSSION: These data do not confirm the presence of disgust recognition deficits in individuals with OCD. In light of the deficits exhibited by one subject with severe OCD, disgust recognition deficits may be confined to an unidentified subset of people with OCD.}, } @article {pmid15197525, year = {2004}, author = {Loftus, A and Murphy, S and McKenna, I and Mon-Williams, M}, title = {Reduced fields of view are neither necessary nor sufficient for distance underestimation but reduce precision and may cause calibration problems.}, journal = {Experimental brain research}, volume = {158}, number = {3}, pages = {328-335}, pmid = {15197525}, issn = {0014-4819}, mesh = {Arm/innervation/physiology ; Biomechanical Phenomena ; Cues ; Depth Perception/physiology ; Feedback/physiology ; Humans ; Neuropsychological Tests ; Observer Variation ; Orientation/*physiology ; Photic Stimulation ; Psychomotor Performance/*physiology ; Sensory Deprivation/*physiology ; Space Perception/*physiology ; Visual Fields/*physiology ; }, abstract = {Watt et al. (Exp Brain Res, 2000, 135:411-416) suggested that a reduced field of view causes objects to appear closer than their physical distance. This suggestion is based on the observation that individuals terminated open-loop prehension prematurely when pretending to grasp a paper rectangle initially viewed through a reduced field of view. We tested Watt et al.'s suggestion in an open-loop pointing task. In experiment 1, 21 participants pointed at targets in three locations (20, 30 and 40 cm relative to the starting position) in three viewing conditions (full, 16 degrees and 4 degrees field of view). No difference in accuracy was found between conditions but the reduced field of view led to an increase in end-point variability across trials. We interpret these results as indicating that a reduced field of view decreases precision but does not necessarily affect object localisation. In experiment 2, we asked participants to reach-and-grasp a real object under the same three open-loop viewing conditions but without vision following movement onset. The experimental design ensured that haptic feedback was available, which could be used to calibrate reaching movements. We found that the reduced field of view caused no changes in grasp but we observed changes in the transport kinematics consistent with increased variability in the perceptual estimate of target location. Notably there were no changes in the spatial path (expected from movements to a closer location). In experiment 3, we repeated the Watt et al. design but removed vision and forced participants to rely on memory. In this condition we found the same undershoots as described by Watt et al. We conclude that a reduced field of view is neither necessary nor sufficient for underestimation and suggest that a reduced field of view decreases precision. This can cause participants to undershoot and/or alter the movement kinematics but we argue that such findings cannot be ascribed unambiguously to perceptual underestimation as they may reflect strategic alterations in behaviour.}, } @article {pmid15168898, year = {2004}, author = {Hutzler, F and Ziegler, JC and Perry, C and Wimmer, H and Zorzi, M}, title = {Do current connectionist learning models account for reading development in different languages?.}, journal = {Cognition}, volume = {91}, number = {3}, pages = {273-296}, doi = {10.1016/j.cognition.2003.09.006}, pmid = {15168898}, issn = {0010-0277}, mesh = {Child ; Child Development ; Female ; Humans ; *Language ; *Learning ; Male ; *Models, Psychological ; *Reading ; }, abstract = {Learning to read a relatively irregular orthography, such as English, is harder and takes longer than learning to read a relatively regular orthography, such as German. At the end of grade 1, the difference in reading performance on a simple set of words and nonwords is quite dramatic. Whereas children using regular orthographies are already close to ceiling, English children read only about 40% of the words and nonwords correctly. It takes almost 4 years for English children to come close to the reading level of their German peers. In the present study, we investigated to what extent recent connectionist learning models are capable of simulating this cross-language learning rate effect as measured by nonword decoding accuracy. We implemented German and English versions of two major connectionist reading models, Plaut et al.'s (Plaut, D. C., McClelland, J. L., Seidenberg, M. S., & Patterson, K. (1996). Understanding normal and impaired word reading: computational principles in quasi-regular domains. Psychological Review, 103, 56-115) parallel distributed model and Zorzi et al.'s (Zorzi, M., Houghton, G., & Butterworth, B. (1998a). Two routes or one in reading aloud? A connectionist dual-process model. Journal of Experimental Psychology: Human Perception and Performance, 24, 1131-1161); two-layer associative network. While both models predicted an overall advantage for the more regular orthography (i.e. German over English), they failed to predict that the difference between children learning to read regular versus irregular orthographies is larger earlier on. Further investigations showed that the two-layer network could be brought to simulate the cross-language learning rate effect when cross-language differences in teaching methods (phonics versus whole-word approach) were taken into account. The present work thus shows that in order to adequately capture the pattern of reading acquisition displayed by children, current connectionist models must not only be sensitive to the statistical structure of spelling-to-sound relations but also to the way reading is taught in different countries.}, } @article {pmid15154168, year = {2004}, author = {Woodard, FJ}, title = {Response to Lynn, et al.'s "Evaluation of Woodard's theory of perceptually oriented hypnosis".}, journal = {Psychological reports}, volume = {94}, number = {2}, pages = {431-436}, doi = {10.2466/pr0.94.2.431-436}, pmid = {15154168}, issn = {0033-2941}, mesh = {Existentialism/psychology ; Gestalt Theory ; Humans ; *Hypnosis ; Individuality ; Models, Psychological ; *Perception ; *Psychological Theory ; Research Design ; }, abstract = {In this article some misunderstandings of Perceptually Oriented Hypnosis presented in the recent evaluation by Lynn, et al. are pointed out. Perceptually Oriented Hypnosis emphasizes individual differences naturally occurring in the experience of everyday life or being-in-the-world and differentiation as major themes to understanding hypnosis. Woodard advocates that qualitative research enhances our understanding of hypnotic experiencing and allows us to examine hypnotic phenomena that elude the laboratory and control settings.}, } @article {pmid15129925, year = {2004}, author = {Kalman, DS}, title = {High-fat diets and performance: a response to Roltsch et al.'s "The effect of diet manipulations on aerobic performance".}, journal = {International journal of sport nutrition and exercise metabolism}, volume = {14}, number = {1}, pages = {2-3; author reply 4-6}, doi = {10.1123/ijsnem.14.1.2}, pmid = {15129925}, issn = {1526-484X}, mesh = {Adaptation, Physiological ; Dietary Carbohydrates/*administration & dosage/metabolism ; Dietary Fats/*administration & dosage/metabolism ; Energy Metabolism/*physiology ; Exercise/*physiology ; Exercise Test ; Humans ; }, } @article {pmid15129837, year = {2004}, author = {Noeker, M}, title = {Epilepsy--improvement of giving the diagnosis between the demands for standardisation versus individualisation.}, journal = {Seizure}, volume = {13}, number = {2}, pages = {95-98}, doi = {10.1016/s1059-1311(03)00148-1}, pmid = {15129837}, issn = {1059-1311}, mesh = {Adaptation, Psychological ; *Disclosure ; Epilepsy/*diagnosis ; Evidence-Based Medicine ; Humans ; Interviews as Topic ; Professional-Patient Relations ; }, abstract = {Starting from Cunningham et al.'s [Seizure 11 (2002) 500] attempt to develop a guideline for giving the diagnosis of childhood epilepsy, the paper discusses the specific difficulties emerging on the way towards a standardisation and development of guidelines for the disclosure of diagnosis. The major objective of disclosure is to enhance positive adaptation towards epilepsy and its associated stressors and treatment demands. Adaptation to a chronic disease, however, depends on subjective processes of stress appraisal and coping response. Supporting adaptation by favourable strategies of disclosure therefore requires to explore and respond to the very personal perception of the medical and psychosocial consequences of the disorder. The broad interindividual variation of subjective anxieties therefore entails the necessity to individualise the procedure of telling the diagnosis in order to maximise its goodness of fit to patient and family characteristics. A procedure is suggested that integrates the individualisation of information provision and counselling, on the one side, and the efforts of standardisation and guideline development, on the other side, in order to improve resulting disclosure practice.}, } @article {pmid15122933, year = {2004}, author = {Leary, MR}, title = {The function of self-esteem in terror management theory and sociometer theory: comment on Pyszczynski et al. (2004).}, journal = {Psychological bulletin}, volume = {130}, number = {3}, pages = {478-82; discussion 483-8}, doi = {10.1037/0033-2909.130.3.478}, pmid = {15122933}, issn = {0033-2909}, mesh = {Anxiety/*prevention & control/*psychology ; Attitude to Death ; Humans ; Interpersonal Relations ; *Psychological Theory ; *Self Concept ; *Social Behavior ; }, abstract = {By applying different standards of evidence to sociometer theory than to terror management theory (TMT), T. Pyszczynski, J. Greenberg, S. Solomon, J. Arndt, and J. Schimel's (2004) review offers an imbalanced appraisal of the theories' merits. Many of Pyszczynski et al.'s (2004) criticisms of sociometer theory apply equally to TMT. and others are based on misconstruals of the theory or misunderstandings regarding how people respond when rejected. Furthermore, much of their review is only indirectly relevant to TMT's position on the function of self-esteem, and the review fails to acknowledge logical and empirical challenges to TMT. A more balanced review suggests that each theory trumps the other in certain respects, both have difficulty explaining all of the evidence regarding self-esteem, and the propositions of each theory can be roughly translated into the concepts of the other. For these reasons, declaring a theoretical winner at this time is premature.}, } @article {pmid15120391, year = {2004}, author = {Chiang, YC and Schaal, BA and Ge, XJ and Chiang, TY}, title = {Range expansion leading to departures from neutrality in the nonsymbiotic hemoglobin gene and the cpDNA trnL-trnF intergenic spacer in Trema dielsiana (Ulmaceae).}, journal = {Molecular phylogenetics and evolution}, volume = {31}, number = {3}, pages = {929-942}, doi = {10.1016/j.ympev.2003.09.017}, pmid = {15120391}, issn = {1055-7903}, mesh = {Cell Nucleus/metabolism ; DNA, Chloroplast ; *DNA, Intergenic ; Exons ; Genes, Plant ; Genetic Variation ; Haplotypes ; Hemoglobins/*genetics ; Introns ; Phylogeny ; Ulmus/*genetics ; }, abstract = {The population genetics and phylogeography of Trema dielsiana in Taiwan were inferred from genetic diversity at the nonsymbiotic hemoglobin gene and the trnL-trnF intergenic spacer of cpDNA. Reduced genetic variation was detected in these two unlinked genes. The gene genealogy of the hemoglobin locus recovered two lineages corresponding to the western and eastern regions of Taiwan. This pattern is compatible with a past fragmentation event revealed by phylogeographical analyses. To distinguish between selective departures from neutrality (i.e., heterogeneous processes) and demographic (homogeneous) processes, Hahn et al.'s heterogeneity test was conducted on the hemoglobin gene. Lack of significant differences in Tajima's D statistics between synonymous and nonsynonymous mutations indicates that homogeneous processes may have played a key role in governing the evolution of the functional locus. Significantly negative Tajima's D estimates for both overall exons and introns of the hemoglobin gene as well as for the cpDNA intergenic spacer support a phylogeographical hypothesis of range expansion after genetic bottlenecks. High level of genetic variation and a negative Tajima's D statistic suggests a possible northern refugium that may have harbored populations during the glacial maximum.}, } @article {pmid15114903, year = {2004}, author = {Spruyt, A and Hermans, D and Pandelaere, M and De Houwer, J and Eelen, P}, title = {On the replicability of the affective priming effect in the pronunciation task.}, journal = {Experimental psychology}, volume = {51}, number = {2}, pages = {109-115}, doi = {10.1027/1618-3169.51.2.109}, pmid = {15114903}, issn = {1618-3169}, mesh = {Adult ; *Affect ; Female ; Humans ; Male ; Random Allocation ; Reproducibility of Results ; *Semantics ; *Verbal Behavior ; *Vocabulary ; }, abstract = {Bargh, Chaiken, Raymond, and Hymes (1996) and Hermans, De Houwer, and Eelen (1994) showed that a valenced target word is pronounced faster after the presentation of an affectively related prime word than after the presentation of an affectively unrelated prime word. This finding is important because it provides crucial evidence for the hypotheses that stimulus evaluation (a) is goal-independent and (b) facilitates the encoding of stimuli that have the same valence. However, recent studies indicate that the affective priming effect is not a reliable finding in the standard pronunciation task. We report the results of a nearly exact replication of Bargh et al.'s (1996) Experiment 2. In line with previous replication studies, we failed to detect the affective priming effect.}, } @article {pmid15105055, year = {2004}, author = {Miller, K and Blumenthal, P and Blanchard, K}, title = {Oral contraceptives and cervical cancer: critique of a recent review.}, journal = {Contraception}, volume = {69}, number = {5}, pages = {347-351}, doi = {10.1016/j.contraception.2003.12.012}, pmid = {15105055}, issn = {0010-7824}, mesh = {Case-Control Studies ; Confounding Factors, Epidemiologic ; Contraceptives, Oral, Hormonal/*adverse effects ; Female ; Humans ; Uterine Cervical Neoplasms/*chemically induced ; }, abstract = {A recent review article by Smith et al. in The Lancet purports to find a causal relationship between long-term use of oral contraceptives (OCs) and cervical cancer. While we endorse the search for such a relationship, we felt it important to critically examine Smith et al.'s review process and, as a result, we have questions about the validity of their conclusions. In our view, the findings of published articles as presented by Smith et al. do not confirm a causal connection between long-term use of OCs and cervical cancer. Our goal is not to conduct another formal review of the evidence, but to evaluate whether Smith et al. have met the burden of proof for establishing a causal relationship. Given the importance of OCs to women the world over, we urge reproductive health professionals to consider this issue carefully before accepting that a causal relationship exists.}, } @article {pmid15103203, year = {2004}, author = {Gong, H and Takami, Y and Amemiya, T and Tozu, M and Ohashi, Y}, title = {Ocular surface in Zn-deficient rats.}, journal = {Ophthalmic research}, volume = {36}, number = {3}, pages = {129-138}, doi = {10.1159/000077325}, pmid = {15103203}, issn = {0030-3747}, mesh = {Animals ; Ascorbic Acid/blood ; Body Weight ; Cornea/pathology ; Deficiency Diseases/blood/pathology ; Eye/*pathology ; Goblet Cells/pathology ; Male ; Microscopy, Electron ; Microscopy, Electron, Scanning ; Rats ; Rats, Inbred WKY ; Trace Elements/blood ; Zinc/blood/*deficiency ; }, abstract = {PURPOSE: We studied the cornea and conjunctiva of Zn-deficient rats with an electron microscope and time-of-flight secondary ion mass spectrometry (TOF-SIMS) to elucidate the role of trace elements in the cornea and conjunctiva.

MATERIALS AND METHODS: Twenty-one-day-old Wistar Kyoto rats were fed a Zn-deficient diet and deionized water for 7 weeks and then killed. The control rats were fed a Zn-deficient diet and deionized water supplemented with 3 mg Zn/100 ml. After 7 weeks on the deficient diet, another group of rats was given drinking water containing 3 mg Zn/100 ml and the usual diet containing 4.7 mg Zn/100 g for 8 weeks for recovery. The cornea and conjunctiva were examined by electron microscopy and TOF-SIMS.

RESULTS: Microvilli and microplicae in the most superficial layer of the epithelium of the Zn-deficient rat conjunctiva and cornea were prominently reduced, and dark cells were significantly increased. The numbers of goblet cells were decreased in the conjunctiva of the Zn-deficient group. Zn, Ca and Al ions were significantly fewer, but K, Fe, Cl and S ions were significantly more numerous in the Zn-deficient group than in the control group. In the cornea of the Zn-deficient group, there was significantly more Cl but less Ca and vitamin C than in the controls.

DISCUSSION: Zn deficiency may interfere with protein, nucleic acid and collagen synthesis through the reduction of Zn-containing enzymes. Myosin-like substance, actin filaments and tonofibrils are important structural components for microvilli and microplicae in the epithelium. Maldevelopment of these structural components may be related to disturbed activities of Zn-containing enzymes in protein and collagen synthesis because of Zn deficiency. In addition, Zn deficiency caused changes in the levels of Zn and other trace elements such as Ca, Al, S, Fe, and Cl and vitamin C.

CONCLUSION: Zn deficiency resulted in poorly developed microvilli and microplicae on the ocular surface tissues, reduced the number of goblet cells and changed the quantity of trace elements and vitamin C.}, } @article {pmid15096300, year = {2004}, author = {Hunter, SC and Boyle, JM}, title = {Appraisal and coping strategy use in victims of school bullying.}, journal = {The British journal of educational psychology}, volume = {74}, number = {Pt 1}, pages = {83-107}, doi = {10.1348/000709904322848833}, pmid = {15096300}, issn = {0007-0998}, mesh = {*Adaptation, Psychological ; Adolescent ; Child ; Child Behavior Disorders/psychology ; *Crime Victims ; Factor Analysis, Statistical ; Female ; Humans ; Male ; Research Design ; *Schools ; Surveys and Questionnaires ; }, abstract = {BACKGROUND: Transactional models of coping (Lazarus & Folkman, 1984) can contribute to our understanding of why some children cope effectively with bullying while others suffer negative outcomes. However, previous research has relied on coping measures that are not comparable with adult measures, restricting investigation of developmental trends. Additionally, previous research has not included appraisals when measuring coping using an established coping measure.

AIMS: To examine the factor structure of a coping measure that is directly comparable with the adult literature; to examine the content of pupils' threat and challenge appraisals concerning bullying; and to examine the relationships between appraisals and coping strategy use within the victims of school bullying.

SAMPLE: Participants were 459 children aged 9 - 14 years.

METHOD: A self-report bullying questionnaire, incorporating Halstead et al.'s (1993) adolescent version of the Ways of Coping Checklist, was completed by participants. Also included were control, threat and challenge appraisal items.

RESULTS: Confirmatory factor analysis confirmed that Halstead et al.'s four-factor model of coping is valid for a population of school bullying victims. Content validity of items used to measure threat and challenge appraisal was demonstrated. Ambiguity of challenge appraisal influenced the use of Wishful Thinking, Seeks Social Support and Problem Focused coping. Wishful Thinking was also influenced by control appraisal. Avoidance coping was not influenced by the appraisals measured.

CONCLUSION: Halstead et al.'s Revised Ways of Coping Checklist can be used to measure coping amongst child and adolescent victims of bullying. Furthermore, including appraisal variables improves our understanding of individual differences between victims' coping strategy choices.}, } @article {pmid15090092, year = {2004}, author = {Gigliotti, E}, title = {Etiology of maternal-student role stress.}, journal = {Nursing science quarterly}, volume = {17}, number = {2}, pages = {156-164}, doi = {10.1177/0894318404263304}, pmid = {15090092}, issn = {0894-3184}, mesh = {Adaptation, Psychological ; Adult ; *Attitude of Health Personnel ; Conflict, Psychological ; Factor Analysis, Statistical ; Family/psychology ; Female ; Gender Identity ; Humans ; Middle Aged ; Models, Nursing ; Models, Psychological ; Mothers/*psychology ; New Jersey ; New York ; Nursing Methodology Research ; Regression Analysis ; Risk Factors ; Social Support ; Stress, Psychological/*etiology/prevention & control/psychology ; Students, Nursing/*psychology ; Systems Analysis ; Women, Working/psychology ; Workload ; }, abstract = {This paper details the refinement and testing of a proposition regarding the age-related effects of psychological involvement in both the maternal role and the student role, and total network support on maternal-student role stress. Results of hierarchical multiple regression analysis showed that the independent variables contribute to an explanation of maternal-student role stress only for women aged 37 years and older. The proposition was further refined. It supports the propositions of both Neuman's systems model and Meleis et al.'s transition framework. Implications for research and practice are discussed.}, } @article {pmid15083880, year = {2004}, author = {La Montagna, G and Meli, R and Criscuolo, T and D'Angelo, S and Valentini, G}, title = {Bioactivity of prolactin in systemic sclerosis.}, journal = {Clinical and experimental rheumatology}, volume = {22}, number = {2}, pages = {145-150}, pmid = {15083880}, issn = {0392-856X}, mesh = {Adolescent ; Adult ; Aged ; Blood Sedimentation ; C-Reactive Protein/analysis ; Cell Division ; Cell Line, Tumor ; Female ; Humans ; Intercellular Adhesion Molecule-1/blood ; Male ; Middle Aged ; Peptide Fragments/blood ; Procollagen/blood ; Prolactin/*blood ; Receptors, Interleukin-2/blood ; Scleroderma, Systemic/*blood/pathology/physiopathology ; Severity of Illness Index ; Skin/pathology ; von Willebrand Factor/analysis ; }, abstract = {OBJECTIVES: To evaluate basal serum prolactin (PRL) levels in systemic sclerosis (SSc) patients with different degrees of skin involvement, and investigate its relationship with some of the clinical and serological parameters of the disease.

METHODS: Basal serum PRL was measured in 44 SSc patients (38 F, 6 M) using a rat NB2 lymphoma line cell proliferation assay. Other parameters measured were: serum aminoterminal propeptide of type III procollagen (PIIINP) by RIA; soluble alpha interleukin-2 receptor (IL-2 sRalpha), serum intercellular adhesion molecule-1 (ICAM-1), von Willebrand factor (vWF) by ELISA; the erythrocyte sedimentation rate (ESR); and C-reactive protein (CRP). Skin and organ/system involvement were assessed according to Medsger et al.'s organ/system severity scale, and global disease activity index according to Valentini et al.

RESULTS: The serum PRL concentration in the SSc patients was 13.8 ng/ml (95%CI from 3.2 to 49.1 ng/ml), similar than that in control subjects (12.8 ng/nl: 95%CI 3.0 to 18.4 ng/ml). Hyperprolactinemia, defined as a level > 20 ng/ml (mean 30.9 ng/ml, median 29.3) was found in a total of 6 cases (13.6%; 95%CI 5.8 to 28%) cases: in 1 out of 6 men (16.7%; 95%CI -26% to 59%) and similarly in 5/38 women (13.2%; 95%CI 1.9% to 24.4%). No correlation was found between PRL levels and SSc subgroup (lcSSc, icSSc, dcSSc), serologial parameters, or the level of disease activity. Finally, no significant correlations were found with clinical or serological variables.

CONCLUSIONS: The findings confirm that mild hyperprolactinemia occurs in at subgroup of SSc patients. However, prospective studies are needed to better define the relationship between PRL and disease activity in scleroderma.}, } @article {pmid15082571, year = {2004}, author = {Gorelick, R and Laubichler, MD}, title = {Decomposing multilocus linkage disequilibrium.}, journal = {Genetics}, volume = {166}, number = {3}, pages = {1581-1583}, pmid = {15082571}, issn = {0016-6731}, mesh = {Alleles ; Biological Evolution ; Epistasis, Genetic ; Gene Frequency ; Genetic Variation ; *Linkage Disequilibrium ; Mathematics ; Models, Genetic ; Probability ; Species Specificity ; }, abstract = {We present a mathematically precise formulation of total linkage disequilibrium between multiple loci as the deviation from probabilistic independence and provide explicit formulas for all higher-order terms of linkage disequilibrium, thereby combining J. Dausset et al.'s 1978 definition of linkage disequilibrium with H. Geiringer's 1944 approach. We recursively decompose higher-order linkage disequilibrium terms into lower-order ones. Our greatest simplification comes from defining linkage disequilibrium at a single locus as allele frequency at that locus. At each level, decomposition of linkage disequilibrium is mathematically equivalent to number theoretic compositions of positive integers; i.e., we have converted a genetic decomposition into a mathematical decomposition.}, } @article {pmid15081882, year = {2004}, author = {Calamari, JE and Wiegartz, PS and Riemann, BC and Cohen, RJ and Greer, A and Jacobi, DM and Jahn, SC and Carmin, C}, title = {Obsessive-compulsive disorder subtypes: an attempted replication and extension of a symptom-based taxonomy.}, journal = {Behaviour research and therapy}, volume = {42}, number = {6}, pages = {647-670}, doi = {10.1016/S0005-7967(03)00173-6}, pmid = {15081882}, issn = {0005-7967}, mesh = {Cluster Analysis ; Female ; Humans ; Male ; Obsessive-Compulsive Disorder/*classification ; Terminology as Topic ; }, abstract = {A symptom-based subgroup taxonomy for obsessive-compulsive disorder (OCD) was evaluated and refined. The Yale-Brown Obsessive-Compulsive Scale symptom checklist was scored and cluster analysis was conducted with a sample of OCD patients (N = 114). Results were compared to Calamari et al.'s (Behaviour Research and Therapy 37 (1999) 113) five subgroup model. Rules for determining the number of subgroups supported a more complex model. In between sample comparisons, a stable contamination subgroup was found in both a five and seven subgroup taxonomy. Between sample stability was not as strong for Harming, Obsessionals, Symmetry, and Certainty subgroups. Hoarding, as a distinctive subgroup, was unstable in separate samples. When the Calamari et al. sample and the present sample were combined (N = 220), we found a reliable Hoarding subgroup. More interpretable and stable models emerged with the combined samples suggesting that large clinical samples are needed to identify OCD subgroups. Greater support was found for a seven subgroup taxonomy based subgroup interpretability and validation measure differences. The potential utility of symptom-based subgroup models of OCD and alternative approaches are discussed. Identification of reliable and valid OCD subtypes may advance theory and treatment.}, } @article {pmid15081699, year = {2004}, author = {Tareq, SM and Tanaka, N and Ohta, K}, title = {Biomarker signature in tropical wetland: lignin phenol vegetation index (LPVI) and its implications for reconstructing the paleoenvironment.}, journal = {The Science of the total environment}, volume = {324}, number = {1-3}, pages = {91-103}, doi = {10.1016/j.scitotenv.2003.10.020}, pmid = {15081699}, issn = {0048-9697}, mesh = {Biomarkers/*analysis ; *Ecosystem ; Environment ; Environmental Monitoring ; Indonesia ; Lignin/*analysis ; Phenols/*analysis ; *Plants ; *Tropical Climate ; }, abstract = {Organic matter of a peat core (3.60 m, 7428 years BP) collected from Rawa Danau, west Java, Indonesia, was analyzed to evaluate the early diagenetic fates of lignin in a tropical wetland and to reconstruct past vegetation and climate changes. Vertical profiles of (Ad/Al)v, (Ad/Al)s, and lambda(8) show that the lignin composition is well preserved in a sub-aqueous environment under reducing conditions. The sedimentary terrigenous plant material at Rawa Danau is comprised predominantly of angiosperm wood. For this kind of tropical, diverse, and dynamic ecosystem, a new vegetation change index called lignin phenol vegetation index (LPVI): LPVI is defined using the lignin phenol composition. This index can sensitively detect terrestrial vegetation changes as well as environmental conditions forcing such changes. The LPVI of the Rawa Danau peat core provides better resolution than other lignin parameters used previously, and reveals four major vegetation change events since the mid-late Holocene. In comparison to other geochemical data (i.e. elemental carbon, isotopes, and hydrocarbons), the LPVI is more sensitive and is able to trace even minor vegetation and climate changes and thus could improve biogeochemical interpretations of peat records.}, } @article {pmid15058869, year = {2004}, author = {van Rossum, JH}, title = {Perceptions of determining factors in athletic achievement: an addendum to Hyllegard, et al. (2003).}, journal = {Perceptual and motor skills}, volume = {98}, number = {1}, pages = {81-85}, doi = {10.2466/pms.98.1.81-85}, pmid = {15058869}, issn = {0031-5125}, mesh = {*Achievement ; Humans ; *Perception ; *Sports ; }, abstract = {In Hyllegard, et al.'s recent study (2003) on the importance of training and talent in athletic achievement, athletes rated only two factors for relevance. This description of relevant factors is too limited, as is indicated in studies with Dutch coaches and athletes. Athletic achievement is determined by more factors than just talent and training.}, } @article {pmid15056302, year = {2004}, author = {Juffer, F and Stams, GJ and van Jzendoorn, MH}, title = {Adopted children's problem behavior is significantly related to their ego resiliency, ego control, and sociometric status.}, journal = {Journal of child psychology and psychiatry, and allied disciplines}, volume = {45}, number = {4}, pages = {697-706}, doi = {10.1111/j.1469-7610.2004.00264.x}, pmid = {15056302}, issn = {0021-9630}, mesh = {Adoption/*psychology ; Child ; Child Behavior Disorders/*psychology ; Comorbidity ; *Ego ; Female ; Humans ; Internal-External Control ; Male ; Personality ; Risk Factors ; *Social Behavior ; Social Dominance ; }, abstract = {BACKGROUND: Many studies have documented that adopted children are at higher risk for behavior problems, but less is known about the correlates of their problem behavior.

METHOD: The correlates of parent-reported and teacher-reported problem behavior in 7-year-old internationally adopted children (N = 176) were investigated by examining these children's ego resiliency, ego control, and sociometric status, and exploring possible risks factors in the home and racial influences.

RESULTS: Using the 25th percentiles lowest and highest scores on ego resiliency and ego control as cut-off criteria, we found that: (1) resilient children were almost free of behavior problems; (2) overcontrolling children showed predominantly internalizing behavior problems (33% at school, and 28% at home); (3) undercontrolling children showed high rates of externalizing behavior problems (50% at school, and 34% at home), and an elevated rate of comorbidity (21% at school, and 21% at home). Adopted children identified by peer report as controversial or rejected had significantly higher externalizing problem scores than popular, average or neglected adopted children. The adopted children did not experience much (racial) discrimination. Nevertheless, children who wished to be white (46%) presented more mother-reported behavior problems.

CONCLUSIONS: Our findings replicate R.W. Robins et al.'s (1996) work on three types of personality functioning: resilients, overcontrollers and undercontrollers (identified by J. Block, 1971), extending the model from adolescent boys to school-aged boys and girls, adopted from Asia and South America. The wish to identify with white parents and white peers may constitute a potential risk factor for internationally adopted children in middle childhood.}, } @article {pmid15053256, year = {2003}, author = {Jaśkowski, P and Werner, I and Verleger, R}, title = {On the translation of some stimulus features to response force.}, journal = {Acta neurobiologiae experimentalis}, volume = {63}, number = {4}, pages = {327-335}, doi = {10.55782/ane-2003-1472}, pmid = {15053256}, issn = {0065-1400}, mesh = {Adolescent ; Adult ; Female ; Humans ; Isometric Contraction/*physiology ; Male ; Muscle, Skeletal/*physiology ; Photic Stimulation ; Reaction Time/physiology ; }, abstract = {Romaiguère et al. (1993) reported an stimulus-response (S-R) experiment in which the participants had to respond to bright or dim stimuli by pressing a key strongly or weakly. Reaction time (RT) for a compatible S-R assignment (bright-strong; dim-weak) was substantially shorter than for an incompatible S-R assignment (dim-strong; bright-weak). This effect was explained as a direct translation of stimulus intensity to response force (RF). In the present study, we looked for other stimulus features that could be directly transferred to RF. We investigated stimulus size (large/small), vertical location (above/below), and brightness (bright/dim). Delays of RT for incompatible trials were found in case of brightness and size, but not location. In a second experiment, we tested whether such a direct translation might even cause changes of spontaneous RF. Without being instructed about RF, participants made simple reactions to stimuli which differed either in location, size or brightness. Indeed, stimulus size affected RF: larger stimuli were associated with stronger responses. In contrast, brightness had no effect. Thus, we replicated and extended Romaiguère et al.'s (1993) finding. However, the direct-translation account for RF variations received only partial support from our data.}, } @article {pmid15049750, year = {2004}, author = {Caplehorn, J}, title = {Comments on Ritter et al.'s report of a comparative trial of LAAM and methadone maintenance.}, journal = {Addiction (Abingdon, England)}, volume = {99}, number = {4}, pages = {509-10; author reply 510-1}, doi = {10.1111/j.1360-0443.2004.00682.x}, pmid = {15049750}, issn = {0965-2140}, mesh = {Heroin Dependence/*rehabilitation ; Humans ; Methadone/*therapeutic use ; Methadyl Acetate/*therapeutic use ; Narcotics/*therapeutic use ; *Patient Compliance ; }, } @article {pmid15046856, year = {2004}, author = {Roberts, JD}, title = {Senior student nurses information seeking skills: a comparative study.}, journal = {Nurse education today}, volume = {24}, number = {3}, pages = {211-218}, doi = {10.1016/j.nedt.2003.12.001}, pmid = {15046856}, issn = {0260-6917}, mesh = {*Education, Nursing ; Female ; Humans ; *Learning ; Male ; Nursing Education Research ; *Problem Solving ; United Kingdom ; }, abstract = {Information seeking is one of the key skills in the problem-solving process. This paper explores and compares the information seeking skills of senior student nurses (n = 253) from three pre-registration nurse education programmes: Registered General Nurse (RGN); diploma Registered Nurse (Diploma RN); and integrated degree. Skills were explored using a paper and pencil simulation exercise. Study findings revealed both similarities and differences between the groups. Few students displayed a holistic approach when acquiring information and the rationale for information requests was cited infrequently. The integrated degree programme participants displayed a more systematic approach to information acquisition, while more RGN programme participants referred to the use of a model. The most favoured model to aid data acquisition was Roper et al.'s [The Elements of Nursing, third ed., Churchill Livingstone, Edinburgh, 1996] Activities of Living Model. The study findings are discussed in the wider context of professional education and practice and the potential for further development of information seeking skills on pre-registration nurse education programmes is noted.}, } @article {pmid15040724, year = {2004}, author = {Roach, R and Trivedi, J}, title = {Comment on Hussain et al.'s 'Cauda equina syndrome'.}, journal = {British journal of neurosurgery}, volume = {18}, number = {1}, pages = {76}, doi = {10.1080/02688690410001660553}, pmid = {15040724}, issn = {0268-8697}, mesh = {Humans ; Polyradiculopathy/*surgery ; Sciatica/surgery ; Sex Ratio ; Treatment Outcome ; }, } @article {pmid15025905, year = {2004}, author = {Clarke, H and Rees, A and Hardy, GE}, title = {The big idea: clients' perspectives of change processes in cognitive therapy.}, journal = {Psychology and psychotherapy}, volume = {77}, number = {Pt 1}, pages = {67-89}, doi = {10.1348/147608304322874263}, pmid = {15025905}, issn = {1476-0835}, mesh = {Adult ; *Attitude to Health ; *Cognitive Behavioral Therapy ; Depression/*therapy ; Female ; Humans ; Male ; Middle Aged ; Patient Satisfaction ; Professional-Patient Relations ; *Self-Assessment ; Treatment Outcome ; }, abstract = {This study reports on analyses carried out by the authors on five 'end of therapy' evaluations conducted with clients who had received a brief course of cognitive therapy for depression. The clients' evaluation was based on Elliott's (1996) Change Interview Schedule. The transcripts were then analysed using grounded theory methods, and arranged into 10 categories and three category clusters. The category clusters included 'the listening therapist', 'the big idea' and 'feeling more comfortable with self'. Clients' reported cognitive and emotional processes fit with Stiles et al.'s (1990) assimilation model.}, } @article {pmid15012955, year = {2004}, author = {Douady, CJ and Scally, M and Springer, MS and Stanhope, MJ}, title = {"Lipotyphlan" phylogeny based on the growth hormone receptor gene: a reanalysis.}, journal = {Molecular phylogenetics and evolution}, volume = {30}, number = {3}, pages = {778-788}, doi = {10.1016/S1055-7903(03)00246-X}, pmid = {15012955}, issn = {1055-7903}, mesh = {Animals ; Classification ; Databases as Topic ; Evolution, Molecular ; Phylogeny ; Receptors, Somatotropin/*genetics ; Sequence Analysis, DNA ; Shrews/*genetics ; }, abstract = {From an evolutionary perspective, "insectivores" have been one of the most important mammalian groups for over a century. Morphologists have successively pruned flying lemurs, elephant shrews, and tree shrews from Insectivora, but have retained chrysochlorids, tenrecs, erinaceids, soricids, talpids, and solenodontids in crown-group Lipotyphla. With the appearance of large molecular data sets, the monophyly of Lipotyphla has proved untenable. Rather, an emerging consensus is that Lipotyphla is a diphyletic taxon comprised of two monophyletic groups, Afrosoricida and Eulipotyphla. A recent paper by Malia et al. [Mol. Phylogenet. Evol. 24 (2002) 91-101] challenged this view and argued that "While the data [Growth Hormone Receptor] were unable to support the orders Lipotyphla, Eulipotyphla, and Tenrecoidea [= Afrosoricida] this was most likely due to the polyphyly of these groups and not to problems associated with the gene itself such as saturation or highly divergent sequences em leader " (p. 100). We analyzed Malia et al.'s original GHR data set (at both nuclear and protein level), an expanded GHR data set that included 49 additional sequences, and a concatenated data set that included GHR, BRCA1, vWF, and A2AB for a diverse selection of lipotyphlan taxa. Although protein analyses proved inconclusive, all analyses at the DNA level clearly show that the statement of Malia et al. is erroneous. Indeed, likelihood analyses with GHR and with the concatenated data set provide more support for Eulipotyphla and Afrosoricida than for competing hypotheses. These results also highlight the potential pitfalls of single-gene and parsimony-only analyses.}, } @article {pmid15008427, year = {2003}, author = {Misawa, K and Nei, M}, title = {Reanalysis of Murphy et al.'s data gives various mammalian phylogenies and suggests overcredibility of Bayesian trees.}, journal = {Journal of molecular evolution}, volume = {57 Suppl 1}, number = {}, pages = {S290-6}, pmid = {15008427}, issn = {0022-2844}, support = {GM20293/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; *Bayes Theorem ; Mammals/*genetics ; Marsupialia/genetics ; *Models, Genetic ; Nuclear Proteins/genetics ; *Phylogeny ; }, abstract = {Murphy and colleagues reported that the mammalian phylogeny was resolved by Bayesian phylogenetics. However, the DNA sequences they used had many alignment gaps and undetermined nucleotide sites. We therefore reanalyzed their data by minimizing unshared nucleotide sites and retaining as many species as possible (13 species). In constructing phylogenetic trees, we used the Bayesian, maximum likelihood (ML), maximum parsimony (MP), and neighbor-joining (NJ) methods with different substitution models. These trees were constructed by using both protein and DNA sequences. The results showed that the posterior probabilities for Bayesian trees were generally much higher than the bootstrap values for ML, MP, and NJ trees. Two different Bayesian topologies for the same set of species were sometimes supported by high posterior probabilities, implying that two different topologies can be judged to be correct by Bayesian phylogenetics. This suggests that the posterior probability in Bayesian analysis can be excessively high as an indication of statistical confidence and therefore Murphy et al.'s tree, which largely depends on Bayesian posterior probability, may not be correct.}, } @article {pmid15006158, year = {2004}, author = {Lee, TW and Robinson, JR}, title = {Drug delivery to the posterior segment of the eye II: development and validation of a simple pharmacokinetic model for subconjunctival injection.}, journal = {Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics}, volume = {20}, number = {1}, pages = {43-53}, doi = {10.1089/108076804772745455}, pmid = {15006158}, issn = {1080-7683}, mesh = {Animals ; *Computer Simulation ; Conjunctiva/*metabolism ; *Drug Delivery Systems ; Injections ; *Models, Biological ; *Pharmacokinetics ; Predictive Value of Tests ; Vitreous Body/*metabolism ; }, abstract = {The aim of this study was to develop and validate a simple pharmacokinetic model for subconjunctival injection so as to study drug delivery to the posterior segment of the eye using the subconjunctival route. Curve-fitting was performed by ModelMaker 4.0 by applying Tsuji et al.'s in vivo data. It was found that drug elimination from the vitreous chamber was slowed by the existence of a peripheral compartment. The validity of this model was ensured because it gives reasonable predictability at two additional doses. This model is invaluable in studying drug delivery to the back of the eye by subconjunctival injection.}, } @article {pmid15005864, year = {2004}, author = {Sullivan, S and Ruffman, T}, title = {Social understanding: How does it fare with advancing years?.}, journal = {British journal of psychology (London, England : 1953)}, volume = {95}, number = {Pt 1}, pages = {1-18}, doi = {10.1348/000712604322779424}, pmid = {15005864}, issn = {0007-1269}, mesh = {Aged ; Aging/*psychology ; Cognition Disorders/*diagnosis/epidemiology ; Female ; Humans ; Intelligence ; Intelligence Tests ; Male ; Middle Aged ; *Psychological Theory ; *Social Perception ; Surveys and Questionnaires ; }, abstract = {Until recently, theory of mind abilities have received little attention beyond the childhood years. However, pioneering work carried out by Happé, Winner, and Brownell (1998) has opened the doors on a new and exciting area of research that examines theory of mind abilities in later years. Happé et al. reported that theory of mind performance was superior in the elderly. Yet, in direct contrast to these findings, Maylor, Moulson, Muncer, and Taylor (2002) report a decline in theory of mind abilities with advancing years. We used Happé et al.'s task and, like Maylor et al., found a decline in theory of mind abilities in the elderly. Yet this deficit was related to a decline in fluid abilities. We then examined whether deficits in social understanding in the elderly could also be independent of fluid abilities. We used two new tasks; identifying emotions from still photos and identifying emotions and cognitions from video clips. Again we found a decline in social understanding in the elderly, and in this case, the decline was independent of changes in fluid abilities.}, } @article {pmid15002877, year = {2003}, author = {Yamada, J}, title = {Articulatory planning in naming single word-kanji characters.}, journal = {Perceptual and motor skills}, volume = {97}, number = {3 Pt 2}, pages = {1332-1334}, doi = {10.2466/pms.2003.97.3f.1332}, pmid = {15002877}, issn = {0031-5125}, mesh = {Adolescent ; Adult ; Humans ; *Language ; *Phonetics ; *Speech Articulation Tests ; Speech Production Measurement ; Time Factors ; *Vocabulary ; }, abstract = {Yamazaki, et al. (1997) rejected word length measured by number of syllables as not significant in accounting for naming latencies for Japanese kanji characters. This study reexamined Yamazaki, et al.'s data and found that monosyllabic characters were named slower than two- and three-syllable characters. This finding is taken as suggesting the presence of an articulatory planning stage in speech production in Japanese.}, } @article {pmid15002853, year = {2003}, author = {Yamada, J and Tamaoka, K}, title = {Measurement errors in voice-key naming latency for Hiragana.}, journal = {Perceptual and motor skills}, volume = {97}, number = {3 Pt 2}, pages = {1100-1106}, doi = {10.2466/pms.2003.97.3f.1100}, pmid = {15002853}, issn = {0031-5125}, mesh = {Adult ; Female ; Humans ; *Language ; Linguistics ; Male ; Phonetics ; Reproducibility of Results ; *Speech Production Measurement ; *Voice ; *Voice Quality ; }, abstract = {This study makes explicit the limitations and possibilities of voice-key naming latency research on single hiragana symbols (a Japanese syllabic script) by examining three sets of voice-key naming data against Sakuma, Fushimi, and Tatsumi's 1997 speech-analyzer voice-waveform data. Analysis showed that voice-key measurement errors can be substantial in standard procedures as they may conceal the true effects of significant variables involved in hiragana-naming behavior. While one can avoid voice-key measurement errors to some extent by applying Sakuma, et al.'s deltas and by excluding initial phonemes which induce measurement errors, such errors may be ignored when test items are words and other higher-level linguistic materials.}, } @article {pmid14969222, year = {2004}, author = {Yowell, AL}, title = {Sweet pain management in newborns.}, journal = {Kentucky nurse}, volume = {52}, number = {1}, pages = {22}, pmid = {14969222}, issn = {0742-8367}, abstract = {Gradin et al.'s (2002) study supported the use of oral glucose to help relieve pain in neonates. The results of this study could be used to support a research utilization project to promote the use of oral glucose in nursing practice. Feasibility issues would include the need to educate nurses on how to incorporate this research in practice. Future research could be done to determine if glucose loses its effectiveness with increasing age or at what age would a different form of analgesic be more effective.}, } @article {pmid14969221, year = {2004}, author = {Lowe, JR}, title = {The effectiveness of alcohol based hand rubs and compliance with hand hygiene.}, journal = {Kentucky nurse}, volume = {52}, number = {1}, pages = {22}, pmid = {14969221}, issn = {0742-8367}, abstract = {Pittet et al.'s (2000) study observed that an increase in compliance with hand hygiene, especially alcohol based hand rubs, was related to a decrease in the rate of nosocomial infections. The results of this study can be used in a group utilization project of providing information on efficacy and compliance issues related to hand hygiene. All HCWs, but most importantly nurses, can recommend hand hygiene programs on specific units to ensure client health and reduce unwanted health care cost. Feasibility issues would include teaching correct hand hygiene technique and compliance for new hospital employees and costs of educational materials. Considerations would be the length of program, location, and implementation strategies. Future research might focus on the use of a smaller sample size, where more control can be obtained, and the use of different hand hygiene techniques in the prevention of nosocomial infections.}, } @article {pmid14959508, year = {2004}, author = {Nuerk, HC and Weger, U and Willmes, K}, title = {On the perceptual generality of the unit-decade compatibility effect.}, journal = {Experimental psychology}, volume = {51}, number = {1}, pages = {72-79}, doi = {10.1027/1618-3169.51.1.72}, pmid = {14959508}, issn = {1618-3169}, mesh = {Adult ; *Cognition ; Humans ; Male ; *Mathematics ; Visual Perception ; }, abstract = {Number magnitude is assumed to be holistically represented along a single mental number line. Recently, we have observed a unit-decade-compatibility effect which is inconsistent with that assumption (Nuerk, Weger, & Willmes, 2001). In two-digit Arabic number comparison, we have demonstrated that compatible comparisons in which separate decade and unit comparisons lead to the same decision (32_47, 3 < 4 and 2 < 7) were faster than incompatible trials (37_52, 3 < 5, but 7 > 2). Because overall distance was matched, a holistic model could not account for the compatibility effect. However, one could argue that the compatibility effect was due to the specific vertical perceptual arrangement of the two-digit numbers in Nuerk et al.'s (2001) experiment where the decade digits and unit digits were presented column-wise above each other. To examine this objection, we studied the perceptual generality of the compatibility effect with diagonal presentation. We replicated the compatibility effect with diagonal presentation. It is concluded that the compatibility effect is not due to encoding characteristics imposed by the perceptual setting of the original experiment. In particular, the assumption of an overall analog magnitude representation for two-digit numbers is not consistent with these data.}, } @article {pmid14769454, year = {2004}, author = {Graneheim, UH and Lundman, B}, title = {Qualitative content analysis in nursing research: concepts, procedures and measures to achieve trustworthiness.}, journal = {Nurse education today}, volume = {24}, number = {2}, pages = {105-112}, doi = {10.1016/j.nedt.2003.10.001}, pmid = {14769454}, issn = {0260-6917}, mesh = {Concept Formation ; Humans ; Interviews as Topic/methods ; Nursing Research/*methods/standards ; Observation/methods ; *Qualitative Research ; Reproducibility of Results ; }, abstract = {Qualitative content analysis as described in published literature shows conflicting opinions and unsolved issues regarding meaning and use of concepts, procedures and interpretation. This paper provides an overview of important concepts (manifest and latent content, unit of analysis, meaning unit, condensation, abstraction, content area, code, category and theme) related to qualitative content analysis; illustrates the use of concepts related to the research procedure; and proposes measures to achieve trustworthiness (credibility, dependability and transferability) throughout the steps of the research procedure. Interpretation in qualitative content analysis is discussed in light of Watzlawick et al.'s [Pragmatics of Human Communication. A Study of Interactional Patterns, Pathologies and Paradoxes. W.W. Norton & Company, New York, London] theory of communication.}, } @article {pmid14769118, year = {2004}, author = {Lance, CE and Foster, MR and Gentry, WA and Thoresen, JD}, title = {Assessor cognitive processes in an operational assessment center.}, journal = {The Journal of applied psychology}, volume = {89}, number = {1}, pages = {22-35}, doi = {10.1037/0021-9010.89.1.22}, pmid = {14769118}, issn = {0021-9010}, mesh = {*Cognition ; *Employee Performance Appraisal ; *Employment ; Humans ; Surveys and Questionnaires ; }, abstract = {The purpose of this study was (a) to provide additional tests of C. E. Lance, Newbolt, et al.'s (2000) situational specificity (vs. method bias) interpretation of exercise effects on assessment center postexercise dimension ratings and (b) to provide competitive tests of salient dimension versus general impression models of assessor within-exercise evaluations of candidate performance. Results strongly support the situational specificity hypothesis and the general impression model of assessor cognitive processes in which assessors first form overall evaluations of candidate performance that then drive more specific dimensional ratings.}, } @article {pmid14769066, year = {2004}, author = {Mitra, S}, title = {Adaptive utilization of optical variables during postural and suprapostural dual-task performance: comment on Stoffregen, Smart, Bardy, and Pagulayan (1999).}, journal = {Journal of experimental psychology. Human perception and performance}, volume = {30}, number = {1}, pages = {28-38}, doi = {10.1037/0096-1523.30.1.28}, pmid = {14769066}, issn = {0096-1523}, mesh = {*Adaptation, Ocular ; Adolescent ; Adult ; *Cognition ; *Fixation, Ocular ; Humans ; Middle Aged ; *Posture ; *Space Perception ; Visual Perception ; }, abstract = {T. A. Stoffregen, L. J. Smart, B. G. Bardy, and R. J. Pagulayan (1999) combined a postural task (upright stance) with a suprapostural task (visual fixation) to show that sway variability was not driven by optic flow in a task-independent manner (autonomous control) but governed by the demands of the supra-postural task (facilitatory control). The present study used a novel combination of Stoffregen et al.'s task conditions but obtained clear evidence of autonomous control and no indication of facilitatory control. The theoretical adequacy of the stabilization-by-looking versus stabilization-of-looking contrast was examined, as was emerging evidence that posture control and common cognitive tasks place concurrent demands on the same capacity-limited resources. An adaptive resource-sharing view of postural-suprapostural multitasking was proposed as an alternative to both the autonomous- and facilitatory-control views.}, } @article {pmid14755833, year = {2004}, author = {Peigneux, P and Van der Linden, M and Garraux, G and Laureys, S and Degueldre, C and Aerts, J and Del Fiore, G and Moonen, G and Luxen, A and Salmon, E}, title = {Imaging a cognitive model of apraxia: the neural substrate of gesture-specific cognitive processes.}, journal = {Human brain mapping}, volume = {21}, number = {3}, pages = {119-142}, pmid = {14755833}, issn = {1065-9471}, mesh = {Adult ; Apraxias/diagnostic imaging/*physiopathology ; Arm/physiology ; Brain/anatomy & histology/diagnostic imaging/physiology ; *Brain Mapping ; Cerebrovascular Circulation/physiology ; Cognition/*physiology ; Female ; *Gestures ; Humans ; Male ; *Models, Neurological ; Neuropsychological Tests ; Psychomotor Performance/physiology ; Tomography, Emission-Computed ; }, abstract = {The present study aimed to ascertain the neuroanatomical basis of an influential neuropsychological model for upper limb apraxia [Rothi LJ, et al. The Neuropsychology of Action. 1997. Hove, UK: Psychology Press]. Regional cerebral blood flow was measured in healthy volunteers using H2 15O PET during performance of four tasks commonly used for testing upper limb apraxia, i.e., pantomime of familiar gestures on verbal command, imitation of familiar gestures, imitation of novel gestures, and an action-semantic task that consisted in matching objects for functional use. We also re-analysed data from a previous PET study in which we investigated the neural basis of the visual analysis of gestures. First, we found that two sets of discrete brain areas are predominantly engaged in the imitation of familiar and novel gestures, respectively. Segregated brain activation for novel gesture imitation concur with neuropsychological reports to support the hypothesis that knowledge about the organization of the human body mediates the transition from visual perception to motor execution when imitating novel gestures [Goldenberg Neuropsychologia 1995;33:63-72]. Second, conjunction analyses revealed distinctive neural bases for most of the gesture-specific cognitive processes proposed in this cognitive model of upper limb apraxia. However, a functional analysis of brain imaging data suggested that one single memory store may be used for "to-be-perceived" and "to-be-produced" gestural representations, departing from Rothi et al.'s proposal. Based on the above considerations, we suggest and discuss a revised model for upper limb apraxia that might best account for both brain imaging findings and neuropsychological dissociations reported in the apraxia literature.}, } @article {pmid14751285, year = {2004}, author = {French, LB and Lanning, CC and Matly, M and Harris-Warrick, RM}, title = {Cellular localization of Shab and Shaw potassium channels in the lobster stomatogastric ganglion.}, journal = {Neuroscience}, volume = {123}, number = {4}, pages = {919-930}, doi = {10.1016/j.neuroscience.2003.08.036}, pmid = {14751285}, issn = {0306-4522}, support = {R01 NS35631/NS/NINDS NIH HHS/United States ; }, mesh = {Analysis of Variance ; Animals ; Blotting, Western/methods ; Delayed Rectifier Potassium Channels ; Ganglia, Invertebrate/*metabolism ; Immunohistochemistry/methods ; Microscopy, Confocal/methods ; Nerve Net/metabolism ; Neuromuscular Junction/metabolism ; Palinuridae ; Peptides/immunology ; Peripheral Nerves/metabolism ; Potassium Channels/chemistry/*metabolism ; *Potassium Channels, Voltage-Gated ; Pylorus/innervation ; Shab Potassium Channels ; Shaw Potassium Channels ; Stomach/*innervation ; }, abstract = {The motor pattern generated by the 14 neurons composing the pyloric circuit in the stomatogastric ganglion (STG) of the spiny lobster, Panulirus interruptus, is organized not only by the synaptic connections between neurons, but also by the characteristic intrinsic electrophysiological properties of the individual cells. These cellular properties result from the unique complement of ion channels that each cell expresses, and the distribution of those channels in the cell membranes. We have mapped the STG expression of shab and shaw, two genes in the Shaker superfamily of potassium channel genes that encode voltage-dependent, non-inactivating channels. Using antibodies developed against peptide sequences from the two channel proteins, we explored the localization and cell-specific expression of the channels. Anti-Shab and anti-Shaw antibodies both stain all the pyloric neurons in the somata, as well as their primary neurites and branch points of large neurites, but to varying degrees between cell types. Staining was weak and irregular (Shaw) or absent (Shab) in the fine neuropil of pyloric neurons, where most synaptic interactions occur. There is a high degree of variability in the staining intensity among neurons of a single cell class. This supports Golowasch et al.'s [J Neurosci 19 (1999) RC33; Neural Comput 11 (1999) 1079] hypothesis that individual cells can have similar firing properties with varying compositions of ionic currents. Both antibodies stain the axons of the peripheral nerves as they enter foregut muscles. We conclude that both Shab and Shaw channels are appropriately localized to contribute to the noninactivating potassium current in the stomatogastric nervous system.}, } @article {pmid14738370, year = {2003}, author = {Thatcher, J and Reeves, S and Dorling, D and Palmer, A}, title = {Motivation, stress, and cortisol responses in skydiving.}, journal = {Perceptual and motor skills}, volume = {97}, number = {3 Pt 1}, pages = {995-1002}, doi = {10.2466/pms.2003.97.3.995}, pmid = {14738370}, issn = {0031-5125}, mesh = {Adult ; Female ; Humans ; Hydrocortisone/*analysis ; Male ; Middle Aged ; *Motivation ; Saliva/*chemistry ; *Sports ; Stress, Psychological/*psychology ; }, abstract = {This study examined metamotivational dominance, metamotivational states, and cortisol responses in skydiving participants. Data were obtained from 23 experienced skydivers 15 min. prior to and following a skydive. Respondents were mainly paratelic-conformist dominant and most occupied the conformist and arousal-seeking states prior to skydiving, assessed respectively, with Apter, et al.'s Motivational Style Profile and Cook, et al.'s measure of metamotivational states. Paratelic-conformist dominance indicates a predisposition towards conformity and a desire to be spontaneous, and the conformist and arousal seeking states reported prior to completing the skydive represent a desire to conform to expected norms but also to seek arousal. There was no significant change in scores for metamotivational state or stress following skydiving. Contrary to expectations, cortisol level prior to skydiving was negatively associated with external stress. These results support the paratelic, but not the negativistic, dominance found in previous samples of risk sport participants (no skydivers). The conformist dominance and pre-dive conformist metamotivational state scores of this sample may be fundamental for adhering to safety regulations imposed on skydivers. To obtain better understanding of this phenomenon, researchers should attempt to measure these variables during, rather than prior to and after, participation in risk sports.}, } @article {pmid14736313, year = {2004}, author = {Zwaan, RA and Madden, CJ}, title = {Updating situation models.}, journal = {Journal of experimental psychology. Learning, memory, and cognition}, volume = {30}, number = {1}, pages = {283-8; discussion 289-91}, doi = {10.1037/0278-7393.30.1.283}, pmid = {14736313}, issn = {0278-7393}, support = {MH-63972/MH/NIMH NIH HHS/United States ; }, mesh = {*Cognition ; Humans ; Reading ; *Semantics ; }, abstract = {The authors examined how situation models are updated during text comprehension. If comprehenders keep track of the evolving situation, they should update their models such that the most current information, the here and now, is more available than outdated information. Contrary to this updating hypothesis, E. J. O'Brien, M. L. Rizzella, J. E. Albrecht, and J. G. Halleran (1998) obtained results suggesting that outdated or incorrect information may still influence the comprehension process. The authors of the current study demonstrate that the nature of E. J. O'Brien et al.'s materials were the likely cause of this pattern of results. Hence, the current authors constructed materials that circumvent identified confounds and in a reading-time experiment obtained evidence supporting the here-and-now hypothesis.}, } @article {pmid14725865, year = {2004}, author = {McCabe, RE and Chudzik, SM and Antony, MM and Young, L and Swinson, RP and Zolvensky, MJ}, title = {Smoking behaviors across anxiety disorders.}, journal = {Journal of anxiety disorders}, volume = {18}, number = {1}, pages = {7-18}, doi = {10.1016/j.janxdis.2003.07.003}, pmid = {14725865}, issn = {0887-6185}, mesh = {Activities of Daily Living ; Adult ; Agoraphobia/*etiology/psychology ; Analysis of Variance ; Anxiety Disorders/etiology ; Chi-Square Distribution ; Female ; Humans ; Male ; Middle Aged ; Obsessive-Compulsive Disorder/*etiology/psychology ; Ontario ; Panic Disorder/*etiology/psychology ; Phobic Disorders/*etiology/psychology ; Smoking/*adverse effects/psychology ; Surveys and Questionnaires ; Time Factors ; }, abstract = {The purpose of this study was to test the theory put forth by Zvolensky et al. [Clin. Psychol. Sci. Pract. 10 (2003) 29] that smoking is specifically associated with panic disorder (PD) and not more generally associated with other anxiety disorders. Smoking behaviors were examined across three anxiety disorders: panic disorder with or without agoraphobia, social phobia (SP), and obsessive-compulsive disorder (OCD). A greater proportion of the PD group (40.4%) reported smoking compared to the SP (20%) and OCD (22.4%) groups. Those in the PD group were also more likely than those in the other groups to report being a heavy smoker (greater than 10 cigarettes daily). No significant interaction between diagnosis and smoking status was found for any of the symptom measures. However, participants who smoked had significantly higher scores than nonsmokers on a number of scales, including measures of depression, general anxiety, and distress. Differences in anxiety sensitivity between smokers and nonsmokers approached significance. These findings provide support for Zvolensky et al.'s [Clin. Psychol. Sci. Pract. 10 (2003) 29] theoretical conceptualization and suggest a specific link between smoking and panic disorder. Further investigation is warranted to determine the causal direction of this association.}, } @article {pmid14723432, year = {2003}, author = {Vaughn, MG and Howard, MO}, title = {Marijuana use and tridimensional personality traits among college students: a response to Hale, Whiteman, Muehl, and Faynberg.}, journal = {Psychological reports}, volume = {93}, number = {3 Pt 1}, pages = {705-706}, doi = {10.2466/pr0.2003.93.3.705}, pmid = {14723432}, issn = {0033-2941}, mesh = {Adult ; Humans ; Marijuana Abuse/*psychology ; Personality Disorders/diagnosis/*etiology ; *Personality Inventory ; Reproducibility of Results ; Students/*psychology ; }, abstract = {Two important issues relevant to Hale, et al.'s 2003 study of temperament and self-reported marijuana use among college students are discussed. First, given the substantial heterogeneity within marijuana-using subject populations, it is key that studies of marijuana users' temperamental traits fully characterize such use across dimensions such as age of onset, quantity and frequency of lifetime, annual, and current use, and related social and health problems. Second, investigations should carefully address issues relating to the temporal ordering of marijuana use and temperamental traits such as novelty seeking and task persistence. Hale, et al., for example, were unable to determine whether self-reported marijuana use contributed to low scores on Persistence (as assessed by the Tridimensional Personality Questionnaire) or was a consequence of low Persistence, or both. Longitudinal studies of diverse populations of marijuana users who are carefully characterized with regard to substance use, comorbid psychiatric conditions, and temperamental traits will substantially increase understanding of the role of temperament and personality in the etiology of marijuana abuse and dependence.}, } @article {pmid14723430, year = {2003}, author = {Lester, D}, title = {Death anxiety, death depression, and death obsession.}, journal = {Psychological reports}, volume = {93}, number = {3 Pt 1}, pages = {695-696}, doi = {10.2466/pr0.2003.93.3.695}, pmid = {14723430}, issn = {0033-2941}, mesh = {Adult ; Anxiety/*psychology ; *Attitude to Death ; Depression/*psychology ; Factor Analysis, Statistical ; Female ; Humans ; Male ; Obsessive Behavior/*psychology ; Surveys and Questionnaires ; }, abstract = {In a sample of 67 students, scores from Templer's and the Collett-Lester death anxiety scales, Templer, et al.'s death depression scale, and Abdel-Khalek's death obsession scale were only moderately associated, suggesting that the scales are measuring somewhat different constructs.}, } @article {pmid14677783, year = {2003}, author = {Kloss, JD and Lisman, SA}, title = {Clinician attributions and disease model perspectives of mentally ill, chemically addicted patients: a preliminary investigation.}, journal = {Substance use & misuse}, volume = {38}, number = {14}, pages = {2097-2107}, doi = {10.1081/ja-120025127}, pmid = {14677783}, issn = {1082-6084}, mesh = {Adaptation, Psychological ; Adult ; Alcoholism/complications/*therapy ; *Attitude of Health Personnel ; *Attitude to Health ; Diagnosis, Dual (Psychiatry)/psychology ; Female ; Humans ; Male ; Mental Health Services ; Middle Aged ; *Models, Psychological ; Problem Solving ; Professional-Patient Relations ; Schizophrenia/complications/diagnosis/*therapy ; Substance Abuse Treatment Centers ; Surveys and Questionnaires ; Workforce ; }, abstract = {Brickman et al.'s (Brickman, P., Rabinowitz, V. C., Coates, D., Cohn, E., Kidder, L. (1982). Models of helping and coping. American Psychologist 37:364-384.) models of helping and coping provided a framework by which to compare clinicians' attributions of blame and control among several hypothetical patients. Sixty-one mental health clinicians (MHCs) and addiction clinicians (ACs)--mostly master's level clinicians and registered nurses--rated attributions toward vignettes that depicted individuals with schizophrenia, alcoholism, and mentally ill, chemically addicted (MICA) classifications in 1995. Results indicate that MHCs attributed more blame to MICA patients than did ACs, but did not differ on their attributions of control. MHCs' and ACs' attributions of blame and control were generally low, consistent with a medical model. However, the endorsement of a disease model of alcoholism did not significantly predict the amount of blame attributed by the clinicians. Implications for treatment planning for MICA patients are discussed.}, } @article {pmid14665791, year = {2004}, author = {Svensson, S and Mansfield, PR}, title = {Escitalopram: superior to citalopram or a chiral chimera?.}, journal = {Psychotherapy and psychosomatics}, volume = {73}, number = {1}, pages = {10-16}, doi = {10.1159/000074435}, pmid = {14665791}, issn = {0033-3190}, mesh = {Adolescent ; Adult ; *Advertising ; Aged ; Antidepressive Agents, Second-Generation/chemistry/*pharmacology ; Citalopram/chemistry/*pharmacology ; Clinical Trials as Topic ; Drug Industry ; Female ; Humans ; Isomerism ; Male ; Middle Aged ; Product Labeling ; Treatment Outcome ; *Truth Disclosure ; }, abstract = {BACKGROUND: Escitalopram is the active isomer of the antidepressant citalopram. In theory single-isomer drugs may be superior but few have been found to have clinically significant advantages. The manufacturer claims that escitalopram has more efficacy and a faster onset of effect than citalopram. The purpose of this study was to assess how far these claims are justified.

METHODS: Relevant trial reports were requested from H. Lundbeck A/S and the Swedish drug regulatory authority. The trials consisted of a pooled analysis of 1,321 patients from one unpublished, one partly published and one published eight-week trial, as well as a 24-week trial with 357 patients published as a poster. The studies compared escitalopram with placebo and/or citalopram in outpatients aged or=18 years who met specified criteria for depression. The trials' quality was assessed with Moncrieff et al.'s quality assessment instrument and the results compared with the claims from the advertisements.

RESULTS: The advertising claims are not justified because they are based on secondary outcomes, non-intention-to-treat analyses and arbitrarily defined subgroups. The subgroup results are inconsistent. Methodological flaws in the trials could account for the differences found. Even if the differences claimed were real they appear too small to justify higher prices.

CONCLUSIONS: On the evidence available to us the manufacturer's claims of superiority for escitalopram over citalopram are unwarranted. The Swedish and Danish drug regulatory authorities reached similar conclusions. This highlights the need for wider dissemination of national authorities' statements to other countries affected by the European Union's mutual recognition procedure.}, } @article {pmid14663858, year = {2004}, author = {Huang, PJ and Wu, ZT}, title = {Inversion of thicknesses of multi-layered structures from eddy current testing measurements.}, journal = {Journal of Zhejiang University. Science}, volume = {5}, number = {1}, pages = {86-91}, doi = {10.1007/BF02839318}, pmid = {14663858}, issn = {1009-3095}, mesh = {*Algorithms ; Computer Simulation ; Connective Tissue/*physiology ; *Electric Impedance ; *Electromagnetic Fields ; *Numerical Analysis, Computer-Assisted ; *Radio Waves ; }, abstract = {Luquire et al.'s impedance change model of a rectangular cross section probe coil above a structure with an arbitrary number of parallel layers was used to study the principle of measuring thicknesses of multi-layered structures in terms of eddy current testing voltage measurements. An experimental system for multi-layered thickness measurement was developed and several fitting models to formulate the relationships between detected impedance/voltage measurements and thickness are put forward using least square method. The determination of multi-layered thicknesses was investigated after inversing the voltage outputs of the detecting system. The best fitting and inversion models are presented.}, } @article {pmid14651295, year = {2003}, author = {Rastle, K and Kinoshita, S and Lupker, SJ and Coltheart, M}, title = {Cross-task strategic effects.}, journal = {Memory & cognition}, volume = {31}, number = {6}, pages = {867-876}, pmid = {14651295}, issn = {0090-502X}, mesh = {*Decision Making ; Humans ; Reaction Time ; *Reading ; Recognition, Psychology ; *Visual Perception ; Vocabulary ; }, abstract = {When easy and difficult items are mixed together, their reading aloud latencies become more homogeneous relative to their presentation in unmixed ("pure") conditions (Lupker, Brown, & Colombo, 1997). We report two experiments designed to investigate the nature of the mechanism that underlies this list composition, or blocking, effect. In Experiment 1, we replicated Lupker et al.'s (1997) blocking effect in the reading aloud task and extended these findings to the visual lexical decision task. In Experiment 2, we found that blocking effects generalized across tasks: The characteristics of stimuli in a visual lexical decision task influenced reading aloud latencies, and vice versa, when visual lexical decision and reading aloud trials were presented alternately in the same experiment. We discuss implications of these results within time-criterion (Lupker et al., 1997) and strength-of-processing (Kello & Plaut, 2000, 2003) theories of strategic processing in reading.}, } @article {pmid14642295, year = {2003}, author = {Rodway, P and Wright, L and Hardie, S}, title = {The valence-specific laterality effect in free viewing conditions: The influence of sex, handedness, and response bias.}, journal = {Brain and cognition}, volume = {53}, number = {3}, pages = {452-463}, doi = {10.1016/s0278-2626(03)00217-3}, pmid = {14642295}, issn = {0278-2626}, mesh = {*Affect ; Brain/*physiology ; Discrimination, Psychological ; Facial Expression ; Female ; Functional Laterality/*physiology ; Humans ; Male ; Reaction Time/*physiology ; Sex Factors ; *Visual Perception ; }, abstract = {The right hemisphere has often been viewed as having a dominant role in the processing of emotional information. Other evidence indicates that both hemispheres process emotional information but their involvement is valence specific, with the right hemisphere dealing with negative emotions and the left hemisphere preferentially processing positive emotions. This has been found under both restricted (Reuter-Lorenz & Davidson, 1981) and free viewing conditions (Jansari, Tranel, & Adophs, 2000). It remains unclear whether the valence-specific laterality effect is also sex specific or is influenced by the handedness of participants. To explore this issue we repeated Jansari et al.'s free-viewing laterality task with 78 participants. We found a valence-specific laterality effect in women but not men, with women discriminating negative emotional expressions more accurately when the face was presented on the left-hand side and discriminating positive emotions more accurately when those faces were presented on the right-hand side. These results indicate that under free viewing conditions women are more lateralised for the processing of facial emotion than are men. Handedness did not affect the lateralised processing of facial emotion. Finally, participants demonstrated a response bias on control trials, where facial emotion did not differ between the faces. Participants selected the left-hand side more frequently when they believed the expression was negative and the right-hand side more frequently when they believed the expression was positive. This response bias can cause a spurious valence-specific laterality effect which might have contributed to the conflicting findings within the literature.}, } @article {pmid14640843, year = {2003}, author = {Lien, MC and Proctor, RW and Ruthroff, E}, title = {Still no evidence for perfect timesharing with two ideomotor-compatible tasks: a reply to Greenwald (2003).}, journal = {Journal of experimental psychology. Human perception and performance}, volume = {29}, number = {6}, pages = {1267-1272}, doi = {10.1037/0096-1523.29.6.1267}, pmid = {14640843}, issn = {0096-1523}, mesh = {Humans ; *Motion Perception ; *Reaction Time ; *Refractory Period, Psychological ; }, abstract = {For 30 years, A. G. Greenwald and H. G. Shulman's (1973) psychological refractory period (PRP) study has been cited as evidence for perfect timesharing with ideomotor (IM)-compatible tasks. Recently, M.-C. Lien, R. W. Proctor, and P. A. Allen (2002) failed to replicate these results and concluded that IM compatibility is neither necessary nor sufficient to eliminate the PRP effect. A. G. Greenwald (2003) attributed Lien et al.'s nonreplication to the use of (a) a non-IM-compatible task, (b) varied trial spacing, and/or (c) inappropriate instructions. The authors of the present article argue that the first 2 factors are not critical and that instructions merely affect the criterion for speed versus accuracy. In each of Greenwald's experiments, dual-task costs were evident on response time or error rates. Furthermore, the small dual-task costs in his study are consistent with a bottleneck model. Thus, Greenwald (2003) does not provide evidence that IM-compatible tasks enable perfect timesharing.}, } @article {pmid14615692, year = {2003}, author = {Droulout, T and Liraud, F and Verdoux, H}, title = {[Relationships between insight and medication adherence in subjects with psychosis].}, journal = {L'Encephale}, volume = {29}, number = {5}, pages = {430-437}, pmid = {14615692}, issn = {0013-7006}, mesh = {Adult ; Antipsychotic Agents/*therapeutic use ; *Attitude to Health ; Comorbidity ; Female ; Hospitalization/statistics & numerical data ; Hospitals, Psychiatric ; Humans ; Male ; Middle Aged ; *Patient Compliance/statistics & numerical data ; Schizophrenia/*drug therapy/epidemiology/rehabilitation ; Severity of Illness Index ; Substance-Related Disorders/epidemiology ; Surveys and Questionnaires ; }, abstract = {BACKGROUND: Poor medication adherence in subjects with psychosis has a high prevalence and a negative impact on clinical outcome. Several studies have reported that a poor level of insight was a strong predictor of poor medi-cation adherence. However, few studies have investigated whether insight was associated with medication adherence, independently from other clinical and treatment characteristics.

OBJECTIVE: To explore the link between insight and medi-cation adherence in subjects with psychosis, and to assess the impact of potential confounding factors on this association.

METHOD: Subjects included in the study were patients aged 60 or less, consecutively admitted in a psychiatric ward, and presenting with at least one psychotic symptom (delusion or hallucination). Medication adherence was assessed using: 1) history of total discontinuation of treatment against medical advice over the 2 weeks before admission; 2) the 7-point rating scale developed by Kemp et al.; 3) the self-report questionnaire Drug Attitude Inventory (DAI). The Scale to assess Unawareness of Mental Disorder (SUMD) was used to measure level of insight. Assessment of symptoms was performed using the Scale for the Assessment of Positive Symptoms (SAPS), the Scale for the Assessment of Negative Symptoms (SANS), and the Calgary Depression Scale (CDS). DSM IV diagnoses were assessed using the Diagnostic Interview for Psychosis (DIP). The associations between level of insight (SUMD scores) and the three measures of medication adherence were explored using the non-parametric Mann-Whitney and Spearman's tests. Logistic regression models giving Odds Ratios (ORs) and 95% confidence intervals (95% CI) were used to examine the impact of potential confounding variables on the associations between level of insight and medication adherence.

RESULTS: 42 patients presenting with schizophrenia broadly defined (n=25) or psychotic mood disorder (n=17) were assessed. Significant associations were found between higher SUMD scores (ie poorer insight) and discontinuation of treatment before admission (z=- 2.6, p=0.009), poor medication adherence rated using the Kemp et al.'s scale (r=- 0.64; p=0.0001), and negative perception of treatment assessed using the DAI (r=- 0.405; p=0.009). The Kemp'scale score and the DAI score were categorised into poor vs. good according to the median for logistic regression analyses. Subjects were 1.7 times more likely (OR=1.7, 95% CI 1.1-2.5, p=0.01) to have discontinued their treatment, 1.9 times more likely (OR=1.9, 95% CI 1.3-2.8), p=0.0003) to have poor medication adherence rated with the Kemp's scale, and 1.8 times (OR=1.8, 95% CI 1.2-2.6, p=0.005) more likely to have a negative perception of the treatment for one point increase at the SUMD score (ie lower level of insight). The associations between SUMD score and the three measures of medication adherence were not modified after adjustment for demographic characteristics (age, gender, educational level, occupational status, marital status) and categorical diagnosis (schizophrenia broadly defined vs. psychotic mood disorder), severity of symptoms (SANS, SAPS, CDS scores), characteristics of the psychotropic treatment, diagnosis of substance or alcohol use disorder, age at onset, and number of previous admissions.

CONCLUSION: The study demonstrates that medication adherence is associated with the level of insight, independently from other patient's demographic and clinical characteristics. The association between low level of insight and poor medication adherence should be confirmed using prospective studies carried out in ambulatory patients. These findings suggest that psycho-educational programs aimed at improving insight should be developed in order to improve medication adherence.}, } @article {pmid14606974, year = {2003}, author = {Vaughan, R and Morrison, L and Miller, E}, title = {The illness representations of multiple sclerosis and their relations to outcome.}, journal = {British journal of health psychology}, volume = {8}, number = {Pt 3}, pages = {287-301}, doi = {10.1348/135910703322370860}, pmid = {14606974}, issn = {1359-107X}, mesh = {Adult ; *Attitude to Health ; Cross-Sectional Studies ; Female ; Humans ; Male ; Middle Aged ; Multiple Sclerosis/pathology/*psychology ; Prognosis ; *Self Concept ; }, abstract = {OBJECTIVES: The main aims of the present study were to explore the illness representations of individuals with multiple sclerosis (MS) and investigate the relationship of these beliefs to outcome. Based on Leventhal et al.'s self-regulation model, the commonly accepted generic five-component structure of illness representations including identity, time-line, consequences, cause, and cure/controllability was used.

DESIGN: A cross-sectional, correlational design was employed for the study. Interrelationships among the illness representation components and the relationships between the components and outcome were explored using Pearson's r. To determine the contribution of the illness representation components to the explained variance in outcome, a series of stepwise multiple regression analyses was used.

METHOD: A total of 99 participants took part in the study. A series of measures were completed to assess (1). illness representations and (2). five specific areas of outcome.

RESULTS: Participants' illness representations of MS were consistent with the medical nature and understanding of this illness indicating that they held the perceptions of a strong illness identity, chronic time-line, no particular cause and no cure. Beliefs in the serious consequences of MS and limited control were also reported. Some important interrelationships among the illness representation components were demonstrated where a strong illness identity, chronic time-line view and perception of low control were related to more serious consequences. Overall, evidence was provided to suggest that illness representations contribute to outcome. The consequences component was associated with, and contributed to, the explained variance for each of the five outcome areas, indicating that the perception that MS has many negative effects on an individual's life was associated with greater levels of difficulty in all of the outcome areas. In addition, for each of the outcome variables, different combinations of illness representation components explained their variance. For example, higher levels of depression were associated with perceptions of a stronger illness identity, more serious consequences, acute time-line, and low control.

CONCLUSION: Overall support is provided for the application of the five-component structure of illness representations to MS and the likely contribution of such beliefs to outcome. The concept of illness representations therefore provides a useful framework for understanding the psychosocial effects of this illness.}, } @article {pmid14604017, year = {2003}, author = {Brugger, P}, title = {Supernumerary phantoms: a comment on Grossi, et al.'s (2002) spare thoughts on spare limbs.}, journal = {Perceptual and motor skills}, volume = {97}, number = {1}, pages = {3-10}, doi = {10.2466/pms.2003.97.1.3}, pmid = {14604017}, issn = {0031-5125}, mesh = {Hallucinations/psychology ; Humans ; Parapsychology ; *Phantom Limb ; Terminology as Topic ; }, abstract = {A recently published case report of a supernumerary phantom limb in a man with left-sided hemiplegia did not take note that this phenomenon has been extensively documented in the neurological literature for well over 100 years. The present comment provides a brief introduction to the clinical and experimental approaches to supernumerary phantom limbs. It also emphasizes the theoretical importance of this condition for understanding the neurological mechanisms subserving the experience of having a body.}, } @article {pmid14599057, year = {2003}, author = {Lacerda, F}, title = {Identifying children at risk for language impairment: screening of communication at 18 months.}, journal = {Acta paediatrica (Oslo, Norway : 1992)}, volume = {92}, number = {9}, pages = {999-1000}, doi = {10.1080/08035250310004982}, pmid = {14599057}, issn = {0803-5253}, mesh = {Communication ; Humans ; Infant ; Language Development Disorders/*diagnosis ; Mass Screening ; }, abstract = {UNLABELLED: The difficulties of early identification of children at risk for language impairment are discussed against a background of other more or less important phenomena.

CONCLUSION: Bruce et al.'s professional screening at 18 mo provides relevant information to detect children at risk for language impairment.}, } @article {pmid14590206, year = {2000}, author = {Brown, LB and Storandt, M}, title = {Sensitivity of category cued recall to very mild dementia of the Alzheimer type.}, journal = {Archives of clinical neuropsychology : the official journal of the National Academy of Neuropsychologists}, volume = {15}, number = {6}, pages = {529-534}, pmid = {14590206}, issn = {0887-6177}, abstract = {We sought to replicate Buschke, Sliwinski, Kulansky, and Lipton's (1997) finding that the Category Cued Recall portion of the Double Memory Test can discriminate individuals with mild dementia of the Alzheimer type (DAT) and healthy older controls. We then attempted to extend this finding to those with very mild DAT. Finally, we compared these results with those of other tests that discriminate DAT from normal aging. Although we replicated Buschke et al.'s finding that the Category Cued Recall portion of the Double Memory Test discriminates effectively between mildly demented people and controls, it was little more effective in detecting very mild DAT than the WMS Logical Memory subtest nor did it add substantially to the discriminative ability of a brief battery of psychometric tests identified previously.}, } @article {pmid14588298, year = {2001}, author = {Obenchain, TG}, title = {Speculum lumbar extraforaminal microdiscectomy.}, journal = {The spine journal : official journal of the North American Spine Society}, volume = {1}, number = {6}, pages = {415-20; discussion 420-1}, doi = {10.1016/s1529-9430(01)00149-8}, pmid = {14588298}, issn = {1529-9430}, mesh = {Diskectomy/*methods ; Female ; Follow-Up Studies ; Humans ; Intervertebral Disc Displacement/*surgery ; Lumbar Vertebrae/*surgery ; Male ; Middle Aged ; Minimally Invasive Surgical Procedures/methods ; Postoperative Complications ; Prospective Studies ; Surgical Instruments ; }, abstract = {BACKGROUND CONTEXT: Public interest, monetary pressures and improving diagnostic techniques have placed an increasing emphasis on minimalism in lumbar disc excision. Current techniques include microlumbar discectomy and minimally invasive spinal surgery. Both are good techniques but may be painful, require a hospital stay and/or are not widely used because of difficulty acquiring the necessary skills. The author therefore developed a less invasive microscopic technique that may be performed on a consistent outpatient basis with easily acquired skills.

PURPOSE: The purpose of this study was to describe a variant of minimally invasive lumbar disc excision, while assessing the effects on a small group of patients.

STUDY DESIGN: The treatment protocol was a prospective community hospital-based case study designed to evaluate a less invasive method of excising herniated lumbar discs residing in the canal, foraminal or far lateral space.

PATIENT SAMPLE: This study is comprised of 50 patients with all anatomic forms of lumbar disc herniations, inside or outside the canal, at all levels except the lumbosacral joint.

OUTCOME MEASURES: Clinical results were measured by return to work time, the criteria of MacNab and by Prolo et al.'s economic and functional criteria.

METHODS: Selection criteria included adult patients with intractable low back and leg pain, plus an imaging study revealing a lumbar disc herniation consistent with the patient's clinical presentation. Mean patient age was 48 years. The male:female ratio was approximately 2:1. All patients failed at least 3 weeks of conservative therapy. Herniations occurred from the L2-3 space through L4-5, with 30 herniations being within and 20 outside the spinal canal. Both contained and extruded/sequestered herniations were treated. Excluded from the study were patients with herniations inside the spinal canal at the L5-S1 level. Surgical approach was by microscopic speculum transforaminal route for discs residing both within and outside the lumbar canal.

RESULTS: The initial 50 consecutive patients had successful technical operations performed on an outpatient basis by this less invasive technique. By the criteria of MacNab (Table 3), 84% (42 of 50) had an excellent or good result, returning to work at a mean time of 3.5 weeks. Per Prolo et al.'s economic scale, 72% were disabled at levels I and II before surgery. Postoperatively, 92% had improved to levels IV and V. Similarly, on his functional scale, 94% functioned at levels I and II before surgery, whereas 88% achieved levels IV and V after surgery. Eighty percent required no pain medications 1 week after surgery. The only complication was an L3 minor nerve root injury as it exited the L3-4 foramen.

CONCLUSION: The author has described a minimally invasive technique for excising herniated discs that is applicable to all types of lumbar herniations, except for those residing in the canal at L5-S1. Clinical outcomes are comparable to those of other forms of discectomy.}, } @article {pmid14585437, year = {2003}, author = {Pomerantz, JR}, title = {Wholes, holes, and basic features in vision.}, journal = {Trends in cognitive sciences}, volume = {7}, number = {11}, pages = {471-473}, doi = {10.1016/j.tics.2003.09.007}, pmid = {14585437}, issn = {1364-6613}, abstract = {A key issue for theories of perception is specifying the primitives used by the visual system to isolate and identify the objects in an image. Although local features are typically suggested, there is good reason to look for global, configural features as primitives too. Chen et al.'s specific proposal of topological features is both explicit and capable of capturing important global information. It may seem surprising that topology can be detected by honeybees, but Chen's results are in keeping with other findings from humans that global properties are sometimes perceived better than local ones and thus might be basic.}, } @article {pmid14581108, year = {2003}, author = {Zelman, DC and Hoffman, DL and Seifeldin, R and Dukes, EM}, title = {Development of a metric for a day of manageable pain control: derivation of pain severity cut-points for low back pain and osteoarthritis.}, journal = {Pain}, volume = {106}, number = {1-2}, pages = {35-42}, doi = {10.1016/s0304-3959(03)00274-4}, pmid = {14581108}, issn = {0304-3959}, mesh = {Activities of Daily Living ; Adult ; Disability Evaluation ; Female ; Health Status ; Humans ; Low Back Pain/*diagnosis/therapy ; Male ; Middle Aged ; Osteoarthritis/*complications ; Pain Measurement/*methods ; Severity of Illness Index ; }, abstract = {The objective of this study was to adapt the concept of 'episode-free day', a metric for measuring symptom relief in daily units, to the clinical outcome literature for persistent pain. The episode-free day metric is widely used in other medical literature, but no analogous measure exists in pain literature. Prior focus groups with this population suggested that a 'Day of Manageable Pain Control' was an appropriate name for the metric. In the present study, in order to derive a statistical criterion for 'Manageable Day', we used Serlin et al.'s (Pain 61 (1995) 277) cut-point derivation method to derive a single cut-point on a 0-10 scale of average pain that divided groups with significant persistent pain optimally on pain-related functional interference. Participants were 194 patients with moderate-severe low back pain (n=96) or osteoarthritis (n=98). For both patient samples, '5' was the cut-point that optimally distinguished groups on pain-related interference. '5-8' and '5-7' were double cut-point solutions that optimally divided LBP and OA samples into three categories (e.g. lowest, medium and highest average pain), respectively. Derived cut-points were confirmed using a variety of measures of functional disability. Together with research that showed that average pain ratings of approximately 5 and below permit increased function and quality of life in patients with moderate to severe low back pain and osteoarthritis, our findings provide support for the use of 0-5 on a 0-10 numeric average pain severity scale as one possible criterion for a Manageable Day.}, } @article {pmid14578772, year = {2003}, author = {Nelson, JL}, title = {Living donors: options and meanings.}, journal = {Transplantation}, volume = {76}, number = {8}, pages = {1267-1269}, doi = {10.1097/01.TP.0000087836.58112.62}, pmid = {14578772}, issn = {0041-1337}, mesh = {*Ethics, Medical ; Humans ; *Kidney Transplantation ; *Living Donors ; Morals ; }, abstract = {Both the phenomenologic study by Lennerling and colleagues and the case study by Dwyer raise interesting moral issues. Lennerling et al.'s finding that prospective kidney donors understood their decisions as "the only option" invites further examination into how donors understand this phrase, because, as ordinarily construed, it seems false; other options do exist for patients undergoing renal failure. Dwyer's case challenges our moral understanding of transplantation at an even deeper level, presenting us with a possible example of an instance of organ provision, not as a "gift" to the recipient, but as a "shield" for a third party. There is no existing moral consensus that surgeons or other health professionals may gravely worsen the health and threaten the lives of healthy people on the grounds that someone other than their patients may be benefited.}, } @article {pmid14555444, year = {2003}, author = {Savitz, DA}, title = {Epidemiologic evidence on the carcinogenicity of metalworking fluids.}, journal = {Applied occupational and environmental hygiene}, volume = {18}, number = {11}, pages = {913-920}, doi = {10.1080/10473220390237539}, pmid = {14555444}, issn = {1047-322X}, mesh = {Carcinogenicity Tests/methods ; Epidemiologic Research Design ; Humans ; Industrial Oils/*toxicity ; Metallurgy/*instrumentation ; Neoplasms/*epidemiology ; Occupational Diseases/*epidemiology ; Occupational Exposure/adverse effects ; }, abstract = {The purpose of this review is to organize and evaluate the epidemiologic evidence regarding the potential carcinogenicity of metalworking fluids. Published literature was initially examined to identify the key contributions, with a strong emphasis on the series of studies by Eisen et al. A key challenge to addressing the issue is the diversity of metalworking fluids, additives, and by-products produced in use, along with the notable changes in the composition and use of such agents over time. Although several smaller cohort studies provided useful data on this issue through the 1980s, the Eisen et al. studies offer unique information given the size of the cohort, sophistication in exposure assessment, and detailed analysis of cancer mortality risks within the cohort as a function of estimated exposure. The most notable associations, based on precision, magnitude, and evidence for increasing risk with increasing exposure are those between straight metalworking fluids and both rectal and laryngeal cancer, as well as soluble metalworking fluids and laryngeal cancer. Further progress will require additional studies of the scale of Eisen et al.'s as well as a more systematic approach to integrating information from toxicology and industrial hygiene into the interpretation of the epidemiologic literature.}, } @article {pmid14552507, year = {2003}, author = {Häfner, H and Maurer, K and Löffler, W and an der Heiden, W and Hambrecht, M and Schultze-Lutter, F}, title = {Modeling the early course of schizophrenia.}, journal = {Schizophrenia bulletin}, volume = {29}, number = {2}, pages = {325-340}, doi = {10.1093/oxfordjournals.schbul.a007008}, pmid = {14552507}, issn = {0586-7614}, mesh = {Adult ; Age Factors ; Disease Progression ; Female ; Humans ; Male ; *Models, Theoretical ; Prognosis ; Schizophrenia/*physiopathology ; *Schizophrenic Psychology ; Sex Factors ; *Social Behavior ; }, abstract = {Using the Interview for the Retrospective Assessment of the Onset of Schizophrenia (IRAOS), we assessed 170 first illness episodes with a nonpsychotic prodromal stage (73% of the population-based Age, Beginning, Course [ABC] study sample of 232 first illness episodes of schizophrenia from a German population of about 1.5 million). Conrad's (1958) and Docherty et al.'s (1978) stage models of the early course presume unidirectional and compelling patterns of symptom manifestation. Using structural equation modeling, we tested the explanatory power of the stages as latent variables and to what extent these models tally with each other and with data on symptom onset. The models neither converged nor were they confirmed. The reasons for and possible implications of this result will be discussed. We also tested, using various techniques, a causal model of the determinants of social course. The only significant predictors of 5-year social outcome turned out to be social development at psychosis onset and the socially adverse illness behavior of young men. The influence of the traditional predictors, age and gender, type of onset (chronic, acute), and symptomatology, was mediated by these two variables assessed at the end of the prodromal stage.}, } @article {pmid14529781, year = {2003}, author = {Brandes, AA and Ermani, M and Amista, P and Basso, U and Vastola, F and Gardiman, M and Iuzzolino, P and Turazzi, S and Rotilio, A and Volpin, L and Mazza, C and Sainati, L and Ammannati, F and Berti, F}, title = {The treatment of adults with medulloblastoma: a prospective study.}, journal = {International journal of radiation oncology, biology, physics}, volume = {57}, number = {3}, pages = {755-761}, doi = {10.1016/s0360-3016(03)00643-6}, pmid = {14529781}, issn = {0360-3016}, mesh = {Adult ; Antineoplastic Combined Chemotherapy Protocols/administration & dosage/therapeutic use ; Cerebellar Neoplasms/mortality/pathology/*therapy ; Disease-Free Survival ; Female ; Humans ; Karnofsky Performance Status ; Male ; Mechlorethamine/administration & dosage ; Medulloblastoma/mortality/pathology/*therapy ; Middle Aged ; Neoplasm Staging ; Postoperative Complications/etiology ; Prednisone/administration & dosage ; Procarbazine/administration & dosage ; Prospective Studies ; Radiotherapy/adverse effects ; Radiotherapy Dosage ; Vincristine/administration & dosage ; }, abstract = {PURPOSE: To assess in a prospective trial the value of prognostic factors and the outcome of medulloblastoma in adults.

METHODS AND MATERIALS: Patients (> or =18 years) with a histologic diagnosis of medulloblastoma were staged according to Chang et al.'s classification (low risk: T1, T2, T3a, M0, and no residual disease after surgery; high risk: T3b-T4, any M+ or postoperative presence of residual tumor). In low-risk patients, treatment consisted of 36 Gy to the craniospinal axis, supplemented by a local tumor dose of 18.8 Gy (total dose of 54.8 Gy). In high-risk patients, 2 cycles of "up-front chemotherapy" were delivered before the same radiation therapy, followed by maintenance chemotherapy if M1, M2, or M3 disease was present.

RESULTS: Over a 12-year period, 36 evaluable patients were enrolled. Progression-free survival (PFS) at 5 years was higher in low-risk patients compared to the high-risk group: 76% +/- 14% (95% confidence interval [CI] = 52%-100%) vs. 61% +/- 11% (95% CI = 42%-87%). Patients with M- disease showed a significantly better outcome than M+ patients, with 75% showing PFS at 5 years vs. 45% (p = 0.01).

CONCLUSION: The overall PFS observed is comparable to that obtained in pediatric series and suggests that a more effective therapy must be developed for high-risk patients.}, } @article {pmid14527528, year = {2003}, author = {Field, AP and Lawson, J}, title = {Fear information and the development of fears during childhood: effects on implicit fear responses and behavioural avoidance.}, journal = {Behaviour research and therapy}, volume = {41}, number = {11}, pages = {1277-1293}, doi = {10.1016/s0005-7967(03)00034-2}, pmid = {14527528}, issn = {0005-7967}, mesh = {Animals ; *Attitude ; *Avoidance Learning ; Child ; Fear/*psychology ; Female ; Humans ; Learning ; Male ; Marsupialia ; Psychological Tests ; Psychology, Child ; }, abstract = {Field, Argyris and Knowles (Behav Res Ther 39 (2001) 1259), and Field, Hamilton, Knowles and Plews (Behav Res Thera 41 (2003) 113) have developed a prospective paradigm for testing Rachman's (Behav Res Ther 15 (1977) 375) proposition that fear information is important in the development of fears and phobias in children. Despite this paradigm being an advance on retrospective reports, the research so far has been restricted to self-reported fear beliefs measured after the information is given. This gives rise to two possible shortcomings: (1) the effects could simply reflect demand characteristics resulting from children conforming to the experimental demands, and (2) although fear information changes beliefs, this might not translate into the behavioural change that would be expected if this information has a powerful effect relevant to the development of pathological fear. This paper describes an experiment that attempts to address these concerns by improving Field et al.'s (2001, 2003) basic paradigm but with the addition of two measures: (1) a behavioural measure of avoidance, and (2) an implicit attitude task that should not be susceptible to deliberate attempts to conform to experimental demands. The result showed that negative and positive information have dramatic, and opposite, effects on self-reported fear beliefs, behavioural avoidance and implicit attitudes. There were no effects of gender on any of these results. This study fully supports Rachman's model and suggests that past work does not merely reflect demand characteristics and that fear information increases behavioural avoidance as well as fear beliefs.}, } @article {pmid14526774, year = {2003}, author = {Crawford, CL}, title = {Omission of interferon alpha information in Nelson at al.'s article.}, journal = {Pediatric research}, volume = {54}, number = {4}, pages = {555-6; author reply 556}, doi = {10.1203/01.PDR.0000084288.17766.0E}, pmid = {14526774}, issn = {0031-3998}, mesh = {Animals ; Cerebral Palsy/*blood/pathology/*physiopathology ; Child ; Humans ; Infant, Newborn ; Infant, Premature ; Interferon-alpha/*blood ; }, } @article {pmid14516222, year = {2003}, author = {Inhoff, AW and Radach, R and Eiter, BM and Skelly, M}, title = {Exterior letters are not privileged in the early stage of visual word recognition during reading: comment on Jordan, Thomas, Patching and Scott-Brown (2003).}, journal = {Journal of experimental psychology. Learning, memory, and cognition}, volume = {29}, number = {5}, pages = {894-899}, doi = {10.1037/0278-7393.29.5.894}, pmid = {14516222}, issn = {0278-7393}, mesh = {*Attention ; Discrimination Learning ; Fixation, Ocular ; Humans ; *Pattern Recognition, Visual ; Problem Solving ; *Reading ; *Semantics ; Set, Psychology ; }, abstract = {Potential sources for the discrepancy between the letter position effects in T. R. Jordan, S. M. Thomas, G. R. Patching, and K. C. Scott-Brown's (2003; see record 2003-07955-013) and D. Briihl and A. W. Inhoff s (1995; see record 1995-20036-001) studies are examined. The authors conclude that the lack of control over where useful information is acquired during reading in Jordan et al.'s study, rather than differences in the orthographic consistency and the availability of word shape information, account for the discrepant effect pattern in the 2 studies. The processing of a word during reading begins before it is fixated, when beginning letters occupy a particularly favorable parafoveal location that is independent of word length. Knowledge of parafoveal word length cannot be used to selectively process exterior letters during the initial phase of visual word recognition.}, } @article {pmid14512072, year = {2003}, author = {Oei, TP and Hasking, P}, title = {Confirmatory factor analysis of the Quitting Time for Alcohol Questionnaire.}, journal = {Addictive behaviors}, volume = {28}, number = {8}, pages = {1487-1495}, doi = {10.1016/s0306-4603(02)00268-x}, pmid = {14512072}, issn = {0306-4603}, mesh = {Adult ; Alcohol Drinking/*psychology ; Factor Analysis, Statistical ; Female ; Humans ; Male ; Motivation ; Psychometrics ; *Surveys and Questionnaires ; Temperance/*psychology ; }, abstract = {The Quitting Time for Alcohol Questionnaire (QTAQ) was developed by Oei et al. in 1999 to provide a tool that could assess the reasons why a person would cease drinking in a single episode. While this tool was observed to have good psychometric properties, including reliability and validity, the findings have not been replicated, in particular, confirmatory factor analysis has not been provided. This study, using 300 community drinkers, attempted to address this shortcoming. Confirmatory factor analysis supported Oei et al.'s research, indicating that the community sample had a three-factor underlying structure, leading to one total score. The findings show that the QTAQ is a valid and reliable instrument for assessing reasons why people cease drinking in a single session.}, } @article {pmid12956826, year = {2003}, author = {Chow, EW and Husted, J and Weksberg, R and Bassett, AS}, title = {Postmaturity in a genetic subtype of schizophrenia.}, journal = {Acta psychiatrica Scandinavica}, volume = {108}, number = {4}, pages = {260-268}, pmid = {12956826}, issn = {0001-690X}, support = {97800/CAPMC/CIHR/Canada ; }, mesh = {Adult ; Birth Weight ; Brain Diseases ; Case-Control Studies ; *Chromosome Deletion ; Chromosomes, Human, Pair 22/*genetics ; Female ; Humans ; Infant, Newborn ; *Infant, Postmature ; Male ; Risk Factors ; Schizophrenia/*genetics/*physiopathology ; }, abstract = {OBJECTIVE: To determine whether postmaturity (gestation > 41 weeks), small for gestational age (SGA), and other pregnancy and birth complications that may elevate risk for neurodevelopmental disorders, are associated with elevated risk for schizophrenia in 22q11 Deletion Syndrome (22qDS), a genetic subtype of schizophrenia.

METHOD: Antepartum and intrapartum features were examined in 20 adults with 22qDS-schizophrenia and three comparison groups: newborn encephalopathy (n = 164) and healthy newborn controls (n = 400) from Badawi et al.'s (Br Med J 1998, 317: 1549) study, and 16 non-psychotic 22qDS adults (22qDS-NP).

RESULTS: Postmaturity (OR 13.0, 95% CI 3.95, 42.77; P < 0.001) and SGA (OR 3.59, 95% CI 1.23, 10.5; P = 0.03) were more prevalent in 22qDS-SZ than controls. Postmaturity was non-significantly more prevalent in 22qDS-SZ than in newborn encephalopathy (P = 0.06) or 22qDS-NP (P = 0.2). SGA showed similar rates in the two 22qDS groups and newborn encephalopathy, but was more prevalent in 22qDS-NP than controls (P = 0.05).

CONCLUSION: The results suggest that postmaturity may be associated with expression of schizophrenia in a 22qDS subtype of schizophrenia. SGA may be a non-specific marker of neurodevelopmental disturbance.}, } @article {pmid12954439, year = {2003}, author = {Baxter, LR}, title = {Basal ganglia systems in ritualistic social displays: reptiles and humans; function and illness.}, journal = {Physiology & behavior}, volume = {79}, number = {3}, pages = {451-460}, doi = {10.1016/s0031-9384(03)00164-1}, pmid = {12954439}, issn = {0031-9384}, mesh = {Animals ; Basal Ganglia/*physiology/*physiopathology ; *Brain Mapping ; *Ceremonial Behavior ; Dominance-Subordination ; Humans ; Lizards ; Magnetic Resonance Imaging ; Male ; Obsessive-Compulsive Disorder/*physiopathology ; Territoriality ; }, abstract = {Complex, situation-specific territorial maintenance routines are similar across living terrestrial vertebrates (=amniotes). Decades ago, Paul MacLean et al., at the Laboratory of Brain Evolution and Behavior of the National Institute of Mental Health, postulated that these are evolutionarily conserved behaviors whose expression is mediated by the similarly conserved amniote basal ganglia and related brain systems (BG systems). Therefore, they undertook studies in nonhuman primates and in small social lizards (the common green anole, Anolis carolinensis) to examine this idea. MacLean et al. also postulated that when BG systems misfunction in humans, behavioral abnormalities result, some of them under the rubric of psychiatric illnesses. Obsessive-compulsive disorder (OCD) was singled out as one likely candidate. In the last dozen years, functional brain imaging studies of OCD patients have validated the contention that this is, in fact, a condition involving dysfunctioning BG systems. Inspired by the MacLean group's original investigations, my colleagues and I have now applied related functional imaging techniques in naturalistic experiments using Anolis to better understand BG systems' roles in the mediation of complex behavioral routines in healthy amniotes. Here, I will review this functional imaging work in primates (man, and a little in monkey) and in lizards. I believe the literature not only supports MacLean et al.'s contentions about BG systems and behavior in general, but also validates Paul MacLean's life-long contention that human behavioral medicine can profit from a broad comparative approach.}, } @article {pmid12939532, year = {2003}, author = {Demura, S and Sato, S and Nakada, M and Minami, M and Kitabayashi, T}, title = {Comparison of estimation accuracy of body density between different hydrostatics weighing methods without head submersion.}, journal = {Journal of physiological anthropology and applied human science}, volume = {22}, number = {4}, pages = {175-179}, doi = {10.2114/jpa.22.175}, pmid = {12939532}, issn = {1345-3475}, mesh = {Adolescent ; Adult ; Anthropometry/*methods ; *Body Composition ; Female ; Head ; Humans ; Hydrostatic Pressure ; *Immersion ; Male ; Predictive Value of Tests ; Reference Values ; Reproducibility of Results ; }, abstract = {This study compared the accuracy of body density (Db) estimation methods using hydrostatic weighing without complete head submersion (HW(withoutHS)) of Donnelly et al. (1988) and Donnelly and Sintek (1984) as referenced to Goldman and Buskirk's approach (1961). Donnelly et al.'s method estimates Db from a regression equation using HW(withoutHS), moreover, Donnelly and Sintek's method estimates it from HW(withoutHS) and head anthropometric variables. Fifteen Japanese males (173.8+/-4.5 cm, 63.6+/-5.4 kg, 21.2+/-2.8 years) and fifteen females (161.4+/-5.4 cm, 53.8+/-4.8 kg, 21.0+/-1.4 years) participated in this study. All the subjects were measured for head length, width and HWs under the two conditions of with and without head submersion. In order to examine the consistency of estimation values of Db, the correlation coefficients between the estimation values and the reference (Goldman and Buskirk, 1961) were calculated. The standard errors of estimation (SEE) were calculated by regression analysis using a reference value as a dependent variable and estimation values as independent variables. In addition, the systematic errors of two estimation methods were investigated by the Bland-Altman technique (Bland and Altman, 1986). In the estimation, Donnelly and Sintek's equation showed a high relationship with the reference (r=0.960, p<0.01), but had more differences from the reference compared with Donnelly et al.'s equation. Further studies are needed to develop new prediction equations for Japanese considering sex and individual differences in head anthropometry.}, } @article {pmid12938611, year = {2003}, author = {Romano, G and Cocchiara, G and Cajozzo, M and Di Bernardo, C and Buscemi, G and Agrusa, A and Maresi, E and Diana, G}, title = {[Endoscopic treatment of gastric carcinoid. Report of a clinical case].}, journal = {Chirurgia italiana}, volume = {55}, number = {4}, pages = {601-604}, pmid = {12938611}, issn = {0009-4773}, mesh = {Carcinoid Tumor/pathology/*surgery ; *Gastroscopy ; Humans ; Male ; Middle Aged ; Stomach Neoplasms/pathology/*surgery ; }, abstract = {We report on a case of a gastric carcinoid of the sporadic type successfully treated by endoscopic electroresection. From January 1998 to October 2002, 1523 gastroscopies were performed in the Palermo University General Emergency Surgery and Organ Transplant Unit. In a 59-year-old man with a history of dyspepsia, a sessile polypoid gastric lesion was observed in the gastric corpus. Laboratory data were normal. The lesion was successfully treated by electroresection. Histological evaluation revealed an 8-mm-diameter well-differentiated neuroendocrine polypoid tumour infiltrating the muscularis mucosa. According to Rindi et al.'s classification, the polyp was a carcinoid of the sporadic type. A two-year follow-up consisting in gastroscopy every 6 months and evaluation of tumour markers and CT scans once a year has so far shown no recurrence. Surgical treatment is the therapy of choice for gastric carcinoids, but endoscopic resection may be a successful alternative in cases of carcinoids measuring less than 1 cm and presenting multricentric growth. Moreover, endoscopy can also be used in patents at high surgical risk.}, } @article {pmid12931918, year = {2003}, author = {Mansfield, PM and Pinto, MB and Parente, DH}, title = {Self-control and credit-card use among college students.}, journal = {Psychological reports}, volume = {92}, number = {3 Pt 2}, pages = {1067-1078}, doi = {10.2466/pr0.2003.92.3c.1067}, pmid = {12931918}, issn = {0033-2941}, mesh = {Adult ; Disruptive, Impulse Control, and Conduct Disorders/*economics/*prevention & control ; Economics ; Female ; Humans ; Male ; *Self Efficacy ; Students/*psychology ; Surveys and Questionnaires ; }, abstract = {This study assessed the relationship between self-control and credit-card use with a convenience sample of 165 traditional-age college students of whom 69 (42%) were women. Students' self-control was measured on Grasmick, et al.'s Self-control Scale, which has six subscales, one of which is Impulsivity. Comparisons were made between those students who paid their cards off each month, called convenience users, and those who carried a monthly balance forward on scores on total self-control and impulsivity, and number of credit cards possessed. A significant difference in self-control scores was found between these two groups and also for mean impulsivity scores. Significantly fewer credit cards were possessed by students who paid their cards off each month than by those who carried a monthly balance.}, } @article {pmid12915111, year = {2003}, author = {Blackwood, B}, title = {Can protocolised-weaning developed in the United States transfer to the United Kingdom context: a discussion.}, journal = {Intensive & critical care nursing}, volume = {19}, number = {4}, pages = {215-225}, doi = {10.1016/s0964-3397(03)00053-3}, pmid = {12915111}, issn = {0964-3397}, mesh = {Evidence-Based Medicine ; Humans ; *Practice Guidelines as Topic ; United Kingdom ; United States ; Ventilator Weaning/*standards ; }, abstract = {Weaning patients from mechanical ventilation using standardised protocols has been demonstrated to be safe and effective in reducing mechanical ventilation time, intensive care unit (ICU) stay and costs. Studies supporting this have all been conducted in the United States of America and weaning protocols are not widely used in the United Kingdom. With such a strong scientific evidence-base for protocolised-weaning, it is unclear why the introduction of evidence-based practice in this area is so low in the UK. There may be a number of reasons for this. First, it may be that the evidence is considered not to apply to different settings, particularly between the USA and UK where there are many differences in health care cultures. Second, it is suggested that the strength of evidence is not the only factor to account for when trying to introduce research evidence into practice [Qual. Health Care 7 (1998) 149]. The context or environment into which the research is to be implemented and how the implementation process is facilitated are equally important factors to be considered. Kitson et al. [Qual. Health Care 7 (1998) 149] argue that the interplay between the three factors of evidence, context and facilitation, enable the successful implementation of evidence-based practice. This discussion paper explores the factors that influence the introduction of weaning protocols. The discussion is structured around the three core elements from Kitson et al.'s conceptual framework and it draws upon examples of UK and USA contextual differences from Northern Ireland (NI) and Virginia (VA).}, } @article {pmid12914806, year = {2003}, author = {Musa, C and Lépine, JP and Clark, DM and Mansell, W and Ehlers, A}, title = {Selective attention in social phobia and the moderating effect of a concurrent depressive disorder.}, journal = {Behaviour research and therapy}, volume = {41}, number = {9}, pages = {1043-1054}, doi = {10.1016/s0005-7967(02)00212-7}, pmid = {12914806}, issn = {0005-7967}, support = {069777//Wellcome Trust/United Kingdom ; }, mesh = {Adult ; Analysis of Variance ; *Association ; *Attention ; Depressive Disorder/*psychology ; Fear/physiology ; Female ; Humans ; Male ; Paired-Associate Learning ; Phobic Disorders/*psychology ; }, abstract = {Studies using the modified Stroop colour naming task have provided results consistent with the hypothesis that social phobia is associated with an attentional bias towards negative social-evaluative words. However, these results could also have arisen as a consequence of non-attentional processes. For this reason, the present study uses a modified version of MacLeod et al.'s (J. Abnorm. Psychol. 95 (1986) 15) dot-probe task, which provides a more direct measure of attention. Patients with social phobia (n=28), patients with social phobia and a concurrent depressive disorder (n=33), and non-patients (n=40) were presented with word pairs each consisting of a neutral word and a threat word. The results indicated that patients with social phobia show an attentional bias towards social-threat words while non-patients tend to avoid social-threat words. Patients with social phobia and a concurrent depressive disorder behaved like non-patients, indicating that concurrent depression abolishes the attentional bias. Physical threat words were also included in the study. The main analysis indicated that social phobia is also associated with an attentional bias to physical threat. However, a post hoc analysis (which requires replication) suggested that the physical threat bias might have arisen because some social phobia patients also had another anxiety disorder in which physical concerns are likely to have been prominent. Overall, the results emphasise the importance of assessing comorbidity when investigating attentional biases.}, } @article {pmid12911517, year = {2003}, author = {Levy, Y and Mukamel, M and Danon, YL}, title = {Response to von Bernuth et al.'s case report.}, journal = {Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology}, volume = {14}, number = {4}, pages = {338-339}, doi = {10.1034/j.1399-3038.2003.00074.x}, pmid = {12911517}, issn = {0905-6157}, mesh = {Abscess/immunology/metabolism/physiopathology ; Autoimmunity/*immunology ; B-Lymphocytes/immunology/*physiology ; Candidiasis, Chronic Mucocutaneous/immunology/metabolism/physiopathology ; Humans ; Immunoglobulin D/immunology/metabolism ; Immunoglobulin E/immunology/metabolism ; Immunoglobulin G/immunology/metabolism ; Immunoglobulin M/immunology/metabolism ; Immunologic Deficiency Syndromes/immunology/*metabolism ; T-Lymphocytes/immunology/*physiology ; T-Lymphocytopenia, Idiopathic CD4-Positive/immunology/metabolism/physiopathology ; }, } @article {pmid12904902, year = {2003}, author = {Pather, N and Partab, P and Singh, B and Satyapal, KS}, title = {The sympathetic contributions to the cardiac plexus.}, journal = {Surgical and radiologic anatomy : SRA}, volume = {25}, number = {3-4}, pages = {210-215}, pmid = {12904902}, issn = {0930-1038}, mesh = {Adolescent ; Adult ; Angina Pectoris/surgery ; Cardiac Surgical Procedures/methods ; Female ; Ganglia, Sympathetic/*anatomy & histology/surgery ; Ganglionectomy ; Heart/*innervation ; Humans ; Male ; Middle Aged ; }, abstract = {Cardiac sympathetic denervation for intractable angina pectoris in patients unsuitable for conventional revascularization is currently gaining popularity since this procedure may be performed via minimally invasive surgery. A thorough understanding of cardiac innervation and its variations is crucial to successfully effect cardiac denervation. This study aimed to demonstrate the cervical and thoracic sympathetic contributions to the cardiac plexus. The cervical and thoracic sympathetic trunks in 21 fetuses and eight adults were micro-dissected bilaterally and documented (n=58 sides). The superior cervical cardiac ramus originated from the superior cervical ganglion (present in all specimens) in 53% of cases. The middle cervical ganglion (incidence 81%) gave rise to the middle cervical cardiac ramus in 88% of cases. The cervico-thoracic ganglion (incidence 85%) gave the cervico-thoracic cardiac ramus in 84%. In the thoracic region, four cardiac rami arose from the T2-T6 segment of the thoracic sympathetic trunk. All cervical and thoracic cardiac rami were traced consistently to the deep cardiac plexus. Khogali et al.'s (1999) success of limited T2-T4 sympathectomy in relieving pain at rest of patients with intractable angina pectoris appears to indicate that a significant afferent pain pathway from the heart is selectively interrupted. The variability in pattern of the cervical ganglia, cardiac rami and cervical contributions to the cardiac plexus does not appear to affect the outcome of limited sympathectomy. The complexity of cardiac pain pathways is not fully understood. The study is continuing and attempts to contribute to defining these cardiac neuronal pathways.}, } @article {pmid12890836, year = {2003}, author = {Proud, G and Lawson, I and McGeoch, K and Burke, F and Miles, JN}, title = {Comments on Coughlin et al.'s paper regarding cold thermography in the objective diagnosis of the hand-arm vibration syndrome.}, journal = {Occupational medicine (Oxford, England)}, volume = {53}, number = {5}, pages = {343}, doi = {10.1093/occmed/kqg014}, pmid = {12890836}, issn = {0962-7480}, mesh = {Arm Injuries/*diagnosis ; Hand Injuries/*diagnosis ; Humans ; Research Design ; Syndrome ; Vibration/*adverse effects ; }, } @article {pmid12850990, year = {2003}, author = {Perruchet, P and Chambaron, S and Ferrel-Chapus, C}, title = {Learning from implicit learning literature: comment on Shea, Wulf, Whitacre, and Park (2001).}, journal = {The Quarterly journal of experimental psychology. A, Human experimental psychology}, volume = {56}, number = {5}, pages = {769-778}, doi = {10.1080/02724980244000657}, pmid = {12850990}, issn = {0272-4987}, mesh = {Humans ; *Learning ; *Literature ; Psychology, Experimental/methods ; }, abstract = {In their analysis of complex motor skill learning, Shea, Wulf, Whitacre, and Park (2001) have overlooked one of the most robust conclusions of the experimental studies on implicit learning conducted during the last decade--namely that participants usually learn things that are different from those that the experimenter expected them to learn. We show that the available literature on implicit learning strongly suggests that the improved performance in Shea et al.'s Experiments 1 and 2 (and similar earlier experiments, e.g., Wulf & Schmidt, 1997) was due to the exploitation of regularities in the target pattern different from those on which the postexperimental interview focused. This rules out the conclusions drawn from the failure of this interview to reveal any explicit knowledge about the task structure on the part of the participants. Similarly, because the information about the task structure provided to an instructed group of participants in Shea et al.'s Experiment 2 did not concern the regularities presumably exploited by the standard, so-called implicit, group, Shea et al.'s claim that explicit knowledge may be less effective than implicit knowledge is misleading.}, } @article {pmid12841456, year = {2003}, author = {Black, SL}, title = {Cannonical [sic] confusions, an illusory allusion, and more: a critique of Haggbloom, et al.'s list of eminent psychologists (2002).}, journal = {Psychological reports}, volume = {92}, number = {3 Pt 1}, pages = {853-857}, doi = {10.2466/pr0.2003.92.3.853}, pmid = {12841456}, issn = {0033-2941}, mesh = {*Eponyms ; History, 20th Century ; Psychology/classification/*history ; }, abstract = {The analysis by Haggbloom, et al. (2002) establishing a list of the most eminent psychologists of the 20th century contains significant errors. In one case the achievements of Walter B. Cannon are misattributed to W. Gary Cannon. Other errors are eponyms misattributed to Margaret F. Washburn, Morton Deutsch, Wolfgang Köhler, and G. Stanley Hall. A further mistake is to miscalculate the statistic for introductory psychology textbook citations for Hans J. Eysenck. These errors have consequences for the ranking of individuals on this list. Care must be taken to guard against such mistakes.}, } @article {pmid12826108, year = {2003}, author = {Curran, W and Benton, CP}, title = {Speed tuning of direction repulsion describes an inverted U-function.}, journal = {Vision research}, volume = {43}, number = {17}, pages = {1847-1853}, doi = {10.1016/s0042-6989(03)00302-x}, pmid = {12826108}, issn = {0042-6989}, mesh = {Adaptation, Ocular/physiology ; Humans ; Motion Perception/*physiology ; Observer Variation ; Optical Illusions/physiology ; Photic Stimulation/methods ; Reaction Time ; }, abstract = {Direction repulsion describes the phenomenon in which observers typically overestimate the direction difference between two superimposed motions moving in different directions (Marshak & Sekuler, Science 205 (1979) 1399). Previous research has found that, when a relatively narrow range of distractor speeds is considered, direction repulsion of a target motion increases monotonically with increasing speed of the distractor motion. We sought to obtain a more complete measurement of this speed-tuning function by considering a wider range of distractor speeds than has previously been used. Our results show that, contrary to previous reports, direction repulsion as a function of distractor speed describes an inverted U-function. For a target of 2.5 deg/s, we demonstrate that the attenuation of repulsion magnitude with high-speed disractors can be largely explained in terms of the reduced apparent contrast of the distractor. However, when we reduce target motion speed, this no longer holds. When considered from the perspective of Edwards et al.'s (Edwards, Badcock, & Smith, Vision Research 38 (1998) 1573) two global-motion channels, our results suggest that direction repulsion is speed dependent when the distractor and target motions are processed by different global-motion channels, but is not speed dependent when both motions are processed by the same, high-speed channel. The implications of these results for models of direction repulsion are discussed.}, } @article {pmid12812744, year = {2003}, author = {Ling, KA}, title = {Using environmental and growth characteristics of plants to detect long-term changes in response to atmospheric pollution: some examples from British beechwoods.}, journal = {The Science of the total environment}, volume = {310}, number = {1-3}, pages = {203-210}, doi = {10.1016/S0048-9697(02)00640-X}, pmid = {12812744}, issn = {0048-9697}, mesh = {Air Pollutants/*adverse effects ; England ; Environmental Monitoring/*methods ; Hydrogen-Ion Concentration ; Light ; *Models, Theoretical ; Nitrogen/*adverse effects ; *Plant Development ; }, abstract = {This study uses the Ellenberg system of plant indicator values, along with Grime et al.'s plant growth strategy values, to investigate the nature of temporal changes in the composition of ground flora in two beechwoods in the Cotswolds region of the UK, currently receiving atmospheric inputs of nitrogen in excess of critical loads. The woods, first surveyed in the early 1960s, were resurveyed in 1998 using the original sampling protocol. Temporal changes in the abundance of individual species at Blackstable West Wood indicate changes in light over time, although decreases in sun species, and both increases and decreases in shade species suggest that this change has been patchy. Analysis of changes in plant community as represented by weighted and unweighted quadrat Ellenberg and CSR scores have yielded more significant results. Blackstable West Wood shows increases in nitrophilic, moist-soil and competitive species accompanied by a decline in stress-tolerant species. In Buckholt Top Wood there has been an increase in sun and moist-soil species, a decrease in competitive species and, when weighted Ellenberg scores are considered, an increase in acid-tolerant species. These changes indicate both the impact of woodland management by selective felling and an underlying influence of enhanced atmospheric deposition especially of nitrogen pollutants. It is concluded that quadrat mean scores are a useful tool especially where few individual species have undergone large temporal changes in abundance. However, lack of correlations between quadrat Ellenberg scores for pH and light on one hand, and their equivalents measured in the field, i.e. soil pH and surrogates for light, such as distance to the nearest tree and tree density, suggest that this approach may not be sensitive enough to pick up small-scale, within site variations. Although harder to interpret, plant strategy scores were found to be a useful additional descriptor, encapsulating a plant's response to a range of environmental factors.}, } @article {pmid12811468, year = {2003}, author = {Calandra, T and Marchetti, O}, title = {Response to van Saene et al.'s comment on "Prevention of severe Candida infections in non-neutropenic, high-risk, critically ill patients".}, journal = {Intensive care medicine}, volume = {29}, number = {7}, pages = {1196}, pmid = {12811468}, issn = {0342-4642}, mesh = {Antifungal Agents/therapeutic use ; Candidiasis/complications/*prevention & control ; *Critical Illness ; Humans ; Switzerland ; }, } @article {pmid12804534, year = {2003}, author = {Abinun, M and Lilic, D and Gagic, N and Pasic, S}, title = {Comment on Plebani et al.'s report.}, journal = {Clinical immunology (Orlando, Fla.)}, volume = {107}, number = {3}, pages = {202-3; author reply 204}, doi = {10.1016/s1521-6616(03)00039-1}, pmid = {12804534}, issn = {1521-6616}, mesh = {Adolescent ; Adult ; Agammaglobulinemia/*complications/*diagnosis/drug therapy/genetics ; Age of Onset ; Bacterial Infections/complications/immunology ; Child ; Child, Preschool ; Chromosomes, Human, X/genetics ; Common Variable Immunodeficiency/complications/diagnosis/drug therapy/immunology ; Genetic Linkage ; Humans ; Immunoglobulins, Intravenous/therapeutic use ; Infant ; Lung Diseases/complications/immunology ; Male ; Retrospective Studies ; Yugoslavia ; }, } @article {pmid12803442, year = {2003}, author = {Takane, Y}, title = {Question hard, answer simply: a comment on Storms et al. (2003).}, journal = {Neuropsychology}, volume = {17}, number = {2}, pages = {321-2; discussion 323-9}, doi = {10.1037/0894-4105.17.2.321}, pmid = {12803442}, issn = {0894-4105}, mesh = {Alzheimer Disease/*psychology ; *Data Interpretation, Statistical ; Humans ; Individuality ; *Semantics ; }, abstract = {It seems clear that, for whatever reasons, the dementia of the Alzheimer type patient group (as well as other patient groups) exhibits behavior that is different from the normal control group. G. Storms, T. Dirikx, J. Saerens, S. Verstraeten, and P. P. De Deyn (2003) rightfully argue that the observed behavior (similarity judgments) does not tell us the source (cause) of the differences between the 2 groups. Rather, the focus of the study should be placed more on finding the ways the 2 groups are different. They also point out various methodological problems in some of the previous attempts to characterize the nature of the differences. Further methodological issues in G. Storms et al.'s study are examined.}, } @article {pmid12802890, year = {2003}, author = {Mansour, AA and Babstock, DM and Penney, JH and Martin, GM and McLean, JH and Harley, CW}, title = {Novel objects in a holeboard probe the role of the locus coeruleus in curiosity: support for two modes of attention in the rat.}, journal = {Behavioral neuroscience}, volume = {117}, number = {3}, pages = {621-631}, doi = {10.1037/0735-7044.117.3.621}, pmid = {12802890}, issn = {0735-7044}, mesh = {Animals ; Attention/*physiology ; Dopamine beta-Hydroxylase/analysis ; Exploratory Behavior/*physiology ; Hot Temperature ; Locus Coeruleus/chemistry/*physiology ; Male ; Photic Stimulation/methods ; Rats ; Rats, Long-Evans ; Water ; }, abstract = {Idazoxan, an alpha 2 adrenoceptor antagonist (2 mg/kg), enhanced novel object investigation in a holeboard in rats as previously reported (V. Devauges & S. J. Sara, 1990). Two weeks of 10 min/day in 37 degrees C water increased dopamine-beta-hydroxylase staining density in the locus coeruleus but did not enhance novel object investigation. In contrast to idazoxan, however, the warm water treatment increased rearing, center entries, and activity, a pattern previously described during tonic infusion of norepinephrine into the hippocampus. Correlations among dopamine-beta-hydroxylase measures and behavior reinforced these tonic norepinephrine/behavior associations. The behavioral effects across the idazoxan and warm water experiments support G. Aston-Jones et al.'s (1999) 2 modes of attention hypothesis for locus coeruleus function: Phasic locus coeruleus activity promotes focused attention; tonic locus coeruleus activity promotes scanning attention.}, } @article {pmid12794268, year = {2003}, author = {Antoniotti, M and Policriti, A and Ugel, N and Mishra, B}, title = {Model building and model checking for biochemical processes.}, journal = {Cell biochemistry and biophysics}, volume = {38}, number = {3}, pages = {271-286}, doi = {10.1385/CBB:38:3:271}, pmid = {12794268}, issn = {1085-9195}, mesh = {Biochemical Phenomena ; Biochemistry ; Computational Biology/*methods ; Computer Simulation ; Humans ; Kinetics ; Mathematical Computing ; *Models, Biological ; Models, Theoretical ; Purines/metabolism ; Software ; }, abstract = {A central claim of computational systems biology is that, by drawing on mathematical approaches developed in the context of dynamic systems, kinetic analysis, computational theory and logic, it is possible to create powerful simulation, analysis, and reasoning tools for working biologists to decipher existing data, devise new experiments, and ultimately to understand functional properties of genomes, proteomes, cells, organs, and organisms. In this article, a novel computational tool is described that achieves many of the goals of this new discipline. The novelty of this system involves an automaton-based semantics of the temporal evolution of complex biochemical reactions starting from the representation given as a set of differential equations. The related tools also provide ability to qualitatively reason about the systems using a propositional temporal logic that can express an ordered sequence of events succinctly and unambiguously. The implementation of mathematical and computational models in the Simpathica and XSSYS systems is described briefly. Several example applications of these systems to cellular and biochemical processes are presented: the two most prominent are Leibler et al.'s repressilator (an artificial synthesized oscillatory network), and Curto- Voit-Sorribas-Cascante's purine metabolism reaction model.}, } @article {pmid12784935, year = {2003}, author = {Greenberg, J and Jonas, E}, title = {Psychological motives and political orientation--the left, the right, and the rigid: comment on Jost et al. (2003).}, journal = {Psychological bulletin}, volume = {129}, number = {3}, pages = {376-82; discussion 383-93}, doi = {10.1037/0033-2909.129.3.376}, pmid = {12784935}, issn = {0033-2909}, mesh = {*Choice Behavior ; Humans ; *Motivation ; *Politics ; Psychological Theory ; }, abstract = {Presenting an impressive model based on a large body of evidence, J. T. Jost, J. Glaser, A.W. Kruglanski, and F. J. Sulloway (2003) proposed that political conservatism uniquely serves epistemic, existential, and ideological needs driven by fears and uncertainties. The authors offer an alternative view based on conceptual considerations, historical events, features of communist ideology and practice, and additional social science research not reviewed by Jost et al. (2003). First, the authors take issue with Jost et al.'s (2003) description of the two core components of political conservatism. Second, they propose that the motives in the model are equally well served by rigid adherence to any extreme ideology regardless of whether it is right wing or left wing.}, } @article {pmid12782505, year = {2003}, author = {Kaufman, AS}, title = {Critique of Vreugdenhil et al.'s study linking PCBs to the play behaviors of Dutch girls and boys.}, journal = {Environmental health perspectives}, volume = {111}, number = {7}, pages = {A380; author reply A380-1}, doi = {10.1289/ehp.111-a380a}, pmid = {12782505}, issn = {0091-6765}, mesh = {Child ; Child Behavior/*drug effects ; Environmental Pollutants/*poisoning ; Female ; *Gender Identity ; Humans ; Male ; Netherlands ; Play and Playthings/*psychology ; Polychlorinated Biphenyls/*poisoning ; Pregnancy ; *Prenatal Exposure Delayed Effects ; Psychometrics ; }, } @article {pmid12776751, year = {2003}, author = {Kinoshita, S and Lupker, SJ}, title = {Priming and attentional control of lexical and sublexical pathways in naming: a reevaluation.}, journal = {Journal of experimental psychology. Learning, memory, and cognition}, volume = {29}, number = {3}, pages = {405-415}, doi = {10.1037/0278-7393.29.3.405}, pmid = {12776751}, issn = {0278-7393}, mesh = {*Attention ; Humans ; Periodicity ; Reaction Time ; Semantics ; *Vocabulary ; }, abstract = {The authors report 3 naming experiments using J. D. Zevin and D. A. Balota's (2000) multiple prime manipulation. They used 2 sets of nonword primes (fast and slow) and low-frequency exception word primes to separate the effects of prime speed from those of prime type. The size of the regularity effect was unaffected by prime type. Relative to the low-frequency exception word prime condition, the frequency effect was reduced in the fast, but not in the slow, nonword prime condition. Lexicality effect size was reduced in both nonword prime conditions, a result consistent with the lexical checking strategy described by S. J. Lupker, P. Brown, and L. Colombo (1997). The authors suggest that these results are better explained in terms of S. J. Lupker et al.'s time-criterion account than J. D. Zevin and D. A. Balota's pathway control hypothesis.}, } @article {pmid12767403, year = {2003}, author = {Balayssac, D and Authier, N and Cayre, A}, title = {Comment regarding Bergmann et al.'s "Assessment of the in vitro and in vivo properties of a 99mTc-labeled inhibitor of the multidrug resistant gene product of P-glycoprotein".}, journal = {Nuclear medicine and biology}, volume = {30}, number = {4}, pages = {455}, doi = {10.1016/s0969-8051(02)00451-1}, pmid = {12767403}, issn = {0969-8051}, mesh = {Animals ; Lethal Dose 50 ; *Medication Errors ; Rats ; Verapamil/*toxicity ; }, } @article {pmid12763700, year = {2003}, author = {Hibbard, S}, title = {A critique of Lilienfeld et al.'s (2000) "The scientific status of projective techniques".}, journal = {Journal of personality assessment}, volume = {80}, number = {3}, pages = {260-271}, doi = {10.1207/S15327752JPA8003_05}, pmid = {12763700}, issn = {0022-3891}, mesh = {Bias ; Humans ; Mental Disorders/*diagnosis/psychology ; Projective Techniques/*standards ; Psychological Tests ; Psychometrics ; Reproducibility of Results ; Research Design ; Rorschach Test/standards ; Surveys and Questionnaires ; }, abstract = {Lilienfeld, Wood, and Garb (2000) published a largely negative critique of the validity and reliability of projective methods, concentrating on the Comprehensive System for the Rorschach (Exner, 1993), 3 systems for coding the Thematic Apperception Test (TAT; Murray, 1943) cards, and human figure drawings. This article is an effort to document and correct what I perceive as errors of omission and commission in the Lilienfeld et al. article. When projective measures are viewed in the light of these corrections, the evidence for the validity and clinical usefulness of the Rorschach and TAT methods is more robust than Lilienfeld et al. represented.}, } @article {pmid12747512, year = {2003}, author = {Myerson, J and Adams, DR and Hale, S and Jenkins, L}, title = {Analysis of group differences in processing speed: Brinley plots, Q-Q plots, and other conspiracies.}, journal = {Psychonomic bulletin & review}, volume = {10}, number = {1}, pages = {224-237}, pmid = {12747512}, issn = {1069-9384}, support = {AG10197/AG/NIA NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aging/*psychology ; Attention ; *Discrimination Learning ; Humans ; *Mental Processes ; Mental Recall ; Middle Aged ; *Models, Statistical ; *Orientation ; *Pattern Recognition, Visual ; Problem Solving ; Psychophysics ; *Reaction Time ; Regression Analysis ; }, abstract = {Researchers in a growing number of areas (including cognitive development, aging, and neuropsychology) use Brinley plots to compare the processing speed of different groups. Ratcliff, Spieler, and McKoon (2000) argued that a Brinley plot is a quantile-quantile (Q-Q) plot and that therefore Brinley plot regression slopes measure standard deviation ratios rather than relative speed of processing. We show that this argument is incorrect. Brinley plots, by definition, are not Q-Q plots; the former are based on unranked data and the latter are based on ranked data. Furthermore, the relationship between standard deviation ratios and slopes is a general property of regression lines and has no implications for the use of Brinley plot regression slopes as processing speed measures. We also show that the relative speed interpretation of Brinley plot slopes is strongly supported by converging evidence from a metaanalysis of visual search, mental rotation, and memory scanning in young and older adults. As to Ratcliff et al.'s hypothesis that age differences in response time are attributable to greater cautiousness on the part of the elderly, rather than true processing speed differences, this hypothesis has been extensively tested in previous studies and found wanting.}, } @article {pmid12740080, year = {2003}, author = {Abrantes, MM and Lamounier, JA and Colosimo, EA}, title = {Comparison of body mass index values proposed by Cole et al. (2000) and Must et al. (1991) for identifying obese children with weight-for-height index recommended by the World Health Organization.}, journal = {Public health nutrition}, volume = {6}, number = {3}, pages = {307-311}, doi = {10.1079/PHN2002426}, pmid = {12740080}, issn = {1368-9800}, mesh = {Body Height ; *Body Mass Index ; Body Weight ; Brazil ; Child ; Child, Preschool ; False Positive Reactions ; Female ; Humans ; Male ; Nutrition Assessment ; Obesity/classification/*diagnosis ; Reference Values ; Sensitivity and Specificity ; World Health Organization ; }, abstract = {OBJECTIVES: To calculate the sensitivity, specificity and agreement of body mass index (BMI) values proposed by Cole et al. (Br. Med. J. 2000; 320: 1) and Must et al. (Am. J. Clin. Nutr. 1991; 53: 839 & 54: 773) with weight-for-height index in the nutritional evaluation of children.

DESIGN: Criterion standards for diagnostic tests.

SETTING: : North-east and south-east Brazil.

SUBJECTS: Two thousand nine hundred and twenty children studied in Life Pattern Research performed by the Brazilian Institute of Geography and Statistics in 1997. Main outcome measures are the sensitivity, specificity and agreement of BMI values proposed by Must et al. (1991) and Cole et al. (2000).

RESULTS: Sensitivity of values proposed by both authors was around 90%. Specificity was almost 100% considering weight-for-height index as the gold standard. The agreement of both values with weight-for-height index, based on kappa results, was good and in pre-school children it was excellent.

CONCLUSIONS: Values proposed by Cole et al. (2000) and Must et al. (1991) should be used carefully to screen obesity in childhood but can be used to "diagnose" overweight children with a very low chance of having false-positive results. Although the values proposed by both authors performed similarly, use of Cole et al.'s values should be encouraged. The latter cover children from 2 to 6 years old; their values are presented for six-month age intervals; they are based on a larger sample from six different countries; and they are related to the definition of adult obesity.}, } @article {pmid12723853, year = {2003}, author = {Melis, M}, title = {Dr. Melis comments on Chakfa, et al.'s article in the October 2002 issue of CRANIO.}, journal = {Cranio : the journal of craniomandibular practice}, volume = {21}, number = {2}, pages = {86}, pmid = {12723853}, issn = {0886-9634}, mesh = {Bite Force ; Female ; Humans ; Isometric Contraction/physiology ; Malocclusion/physiopathology/therapy ; Muscle, Skeletal/*physiology ; Neck Muscles/*physiology ; *Vertical Dimension ; }, } @article {pmid12708508, year = {2003}, author = {Hamlett, A and Ryan, L and Serrano-Trespalacios, P and Wolfinger, R}, title = {Mixed models for assessing correlation in the presence of replication.}, journal = {Journal of the Air & Waste Management Association (1995)}, volume = {53}, number = {4}, pages = {442-450}, doi = {10.1080/10473289.2003.10466174}, pmid = {12708508}, issn = {1096-2247}, support = {ES00002/ES/NIEHS NIH HHS/United States ; ES05947/ES/NIEHS NIH HHS/United States ; ES07142/ES/NIEHS NIH HHS/United States ; }, mesh = {Environmental Monitoring/*statistics & numerical data ; *Models, Theoretical ; Reproducibility of Results ; }, abstract = {The need to assess correlation in settings where multiple measurements are available on each of the variables of interest often arises in environmental science. However, this topic is not covered in introductory statistics texts. Although several ad hoc approaches can be used, they can easily lead to invalid conclusions and to a difficult choice of an appropriate measure of the correlation. Lam et al. approached this problem by using maximum likelihood estimation in cases where the replicate measurements are linked over time, but the method requires specialized software. We reanalyze the data of Lam et al. using PROC MIXED in SAS and show how to obtain the parameter estimates of interest with just a few lines of code. We then extend Lam et al.'s method to settings where the replicate measurements are not linked. Analysis of the unlinked case is illustrated with data from a study designed to assess correlations between indoor and outdoor measurements of benzene concentration in the air.}, } @article {pmid12702690, year = {2003}, author = {Hardy, OJ and Charbonnel, N and Fréville, H and Heuertz, M}, title = {Microsatellite allele sizes: a simple test to assess their significance on genetic differentiation.}, journal = {Genetics}, volume = {163}, number = {4}, pages = {1467-1482}, pmid = {12702690}, issn = {0016-6731}, mesh = {Centaurea/genetics ; Computer Simulation ; *Data Interpretation, Statistical ; Genetics, Population/*statistics & numerical data ; *Microsatellite Repeats ; }, abstract = {The mutation process at microsatellite loci typically occurs at high rates and with stepwise changes in allele sizes, features that may introduce bias when using classical measures of population differentiation based on allele identity (e.g., F(ST), Nei's Ds genetic distance). Allele size-based measures of differentiation, assuming a stepwise mutation process [e.g., Slatkin's R(ST), Goldstein et al.'s (deltamu)(2)], may better reflect differentiation at microsatellite loci, but they suffer high sampling variance. The relative efficiency of allele size- vs. allele identity-based statistics depends on the relative contributions of mutations vs. drift to population differentiation. We present a simple test based on a randomization procedure of allele sizes to determine whether stepwise-like mutations contributed to genetic differentiation. This test can be applied to any microsatellite data set designed to assess population differentiation and can be interpreted as testing whether F(ST) = R(ST). Computer simulations show that the test efficiently identifies which of F(ST) or R(ST) estimates has the lowest mean square error. A significant test, implying that R(ST) performs better than F(ST), is obtained when the mutation rate, mu, for a stepwise mutation process is (a) >/= m in an island model (m being the migration rate among populations) or (b) >/= 1/t in the case of isolated populations (t being the number of generations since population divergence). The test also informs on the efficiency of other statistics used in phylogenetical reconstruction [e.g., Ds and (deltamu)(2)], a nonsignificant test meaning that allele identity-based statistics perform better than allele size-based ones. This test can also provide insights into the evolutionary history of populations, revealing, for example, phylogeographic patterns, as illustrated by applying it on three published data sets.}, } @article {pmid12690829, year = {2003}, author = {Grodner, D and Gibson, E and Argaman, V and Babyonyshev, M}, title = {Against repair-based reanalysis in sentence comprehension.}, journal = {Journal of psycholinguistic research}, volume = {32}, number = {2}, pages = {141-166}, pmid = {12690829}, issn = {0090-6905}, mesh = {*Cognition ; Humans ; Reading ; *Speech Perception ; Time Factors ; Verbal Behavior ; }, abstract = {Structural reanalysis is generally assumed to be representation-preserving, whereby the initial analysis is manipulated or repaired to arrive at a new structure. This paper contends that the theoretical and empirical basis for such approaches is weak. A conceptually simpler alternative is that the processor reprocesses (some portion of) the input using just those structure-building operations available in first-pass parsing. This reprocessing is a necessary component of any realistic processing model. By contrast, the structural revisions required for second-pass repair are more powerful than warranted by the abilities of the first-pass parser. This paper also reviews experimental evidence for repair presented by Sturt, Pickering, and Crocker (1999). We demonstrate that the Sturt et. al. findings are consistent with a reprocessing account and present a self-paced reading experiment intended to tease apart the repair and reprocessing accounts. The results support a reprocessing interpretation of Sturt et. al.'s data, rendering a repair-based explanation superfluous.}, } @article {pmid12679044, year = {2003}, author = {Cherubini, P and Mazzocco, K and Rumiati, R}, title = {Rethinking the focusing effect in decision-making.}, journal = {Acta psychologica}, volume = {113}, number = {1}, pages = {67-81}, doi = {10.1016/s0001-6918(02)00155-5}, pmid = {12679044}, issn = {0001-6918}, mesh = {Adult ; *Attention ; *Decision Making ; Female ; Humans ; Male ; Random Allocation ; }, abstract = {According to Legrenzi et al. [Cognition 49 (1993) 37], in making a choice people consider only the alternatives explicitly represented in their mental model of the decision situation. Their idea has found empirical support in the "focusing effect": Individuals focus on the alternatives explicitly stated in the problem context, and do not take into account other possibilities. In their original study, Legrenzi and colleagues considered only one factor to account for the explicit representation of an alternative--i.e., its explicit verbal formulation in the decision problem. Recent theories of relevance and information gain can help articulate their original idea, suggesting that individuals explicitly represent relevant alternatives, whether or not they are explicitly formulated in the decision problem. In three experiments we first replicated Legrenzi et al.'s original experiment, and then showed that the explicit verbal mention of an alternative is neither sufficient nor necessary to focus on it. The results suggest that individuals are able to consider relevant alternatives, even when they are not made explicit in the verbal formulation of a decision problem.}, } @article {pmid12674731, year = {2003}, author = {DuPaul, GJ}, title = {Assessment of ADHD symptoms: comment on Gomez et al. (2003).}, journal = {Psychological assessment}, volume = {15}, number = {1}, pages = {115-117}, doi = {10.1037/1040-3590.15.1.115}, pmid = {12674731}, issn = {1040-3590}, mesh = {Attention Deficit Disorder with Hyperactivity/*diagnosis ; Child ; Humans ; *Surveys and Questionnaires ; }, abstract = {R. Gomez, G. L. Burns, J. A. Walsh, and M. A. de Moura (2003) examined the degree to which parent and teacher ratings of attention-deficit/hyperactivity disorder (ADHD) symptoms are accounted for by trait, source, and error variance. The importance and limitations of Gomez et al.'s findings are discussed in the context of clinical and research assessments of children suspected of having ADHD. Gomez et al.'s findings make clear that multimethod and multisource assessment protocols should be used in diagnosing children with this disorder. Further, clinicians and researchers must avoid relying too heavily on 1 source of data when evaluating the severity and frequency of ADHD symptoms.}, } @article {pmid12669746, year = {2003}, author = {Macken, WJ and Tremblay, S and Houghton, RJ and Nicholls, AP and Jones, DM}, title = {Does auditory streaming require attention? Evidence from attentional selectivity in short-term memory.}, journal = {Journal of experimental psychology. Human perception and performance}, volume = {29}, number = {1}, pages = {43-51}, doi = {10.1037//0096-1523.29.1.43}, pmid = {12669746}, issn = {0096-1523}, mesh = {Analysis of Variance ; *Attention ; *Auditory Perception ; Humans ; *Memory, Short-Term ; Mental Recall ; Perceptual Masking ; Pitch Discrimination ; Psychological Theory ; Sound Localization ; }, abstract = {R. P. Carlyon, R. Cusack, J. M. Foxton, and I. H. Robertson (2001) have argued that attention is crucial for auditory streaming. The authors review R. P. Carlyon et al.'s (2001) arguments and suggest that a pertinent literature, the irrelevant sound paradigm--demonstrating preattentive auditory streaming--has been overlooked. In illustration of this alternative approach, the authors include a novel single experiment demonstrating the impact of preattentive auditory streaming on short-term serial memory. It is concluded that R. P. Carlyon et al.'s (2001) results do not definitively demonstrate that auditory streaming processes are dependent on attention; indeed, they are compatible with alternative accounts of the relationship between perceptual organization and attention.}, } @article {pmid12659640, year = {2003}, author = {Espeland, A and Baerheim, A}, title = {Factors affecting general practitioners' decisions about plain radiography for back pain: implications for classification of guideline barriers--a qualitative study.}, journal = {BMC health services research}, volume = {3}, number = {1}, pages = {8}, pmid = {12659640}, issn = {1472-6963}, mesh = {Adult ; Attitude of Health Personnel ; Decision Making ; Family Practice/*standards ; Female ; Focus Groups ; Guideline Adherence/*statistics & numerical data ; Health Care Surveys ; Humans ; Low Back Pain/*diagnostic imaging ; Lumbar Vertebrae/*diagnostic imaging ; Male ; Middle Aged ; Norway ; Patient Satisfaction ; Physicians, Family/*psychology ; *Practice Guidelines as Topic ; Practice Patterns, Physicians'/*statistics & numerical data ; Radiography ; Sampling Studies ; }, abstract = {BACKGROUND: General practitioners often diverge from clinical guidelines regarding spine radiography. This study aimed to identify and describe A) factors general practitioners consider may affect their decisions about ordering plain radiography for back pain and B) barriers to guideline adherence suggested by such factors.

METHODS: Focus group interviews regarding factors affecting ordering decisions were carried out on a diverse sample of Norwegian general practitioners and were analysed qualitatively. Results of this study and two qualitative studies from the Netherlands and USA on use of spine radiography were interpreted for barriers to guideline adherence. These were compared with an existing barrier classification system described by Dr Cabana's group.

RESULTS: The factors which Norwegian general practitioners considered might affect their decisions about ordering plain radiography for back pain concerned the following broader issues: clinical ordering criteria, patients' wishes for radiography and the general practitioner's response, uncertainty, professional dignity, access to radiology services, perception of whether the patient really was ill, sense of pressure from other health care providers/social security, and expectations about the consequences of ordering radiography. The three studies suggested several attitude-related and external barriers as classified in a previously reported system described by Dr Cabana in another study. Identified barriers not listed in this system were: lack of expectancy that guideline adherence will lead to desired health care process, emotional difficulty with adherence, improper access to actual/alternative health care services, and pressure from health care providers/organisations.

CONCLUSIONS: Our findings may help implement spine radiography guidelines. They also indicate that Cabana et al.'s barrier classification system needs extending. A revised system is proposed.}, } @article {pmid12627753, year = {2003}, author = {Sperber, S and Spinnler, H}, title = {Covert person recognition: its fadeout in a case of temporal lobe degeneration.}, journal = {Cortex; a journal devoted to the study of the nervous system and behavior}, volume = {39}, number = {1}, pages = {57-67}, doi = {10.1016/s0010-9452(08)70074-1}, pmid = {12627753}, issn = {0010-9452}, mesh = {*Face ; Famous Persons ; Female ; Humans ; Learning ; Middle Aged ; Nerve Degeneration/*psychology ; *Pattern Recognition, Visual ; Prosopagnosia/*psychology ; *Temporal Lobe ; Time Factors ; }, abstract = {Covert person recognition was investigated longitudinally over a three-year period in a patient suffering from "Crossmodal Familiar Person Agnosia", possibly due to a fronto-temporal dementia in its right temporal variant (Gentileschi et al., 2001). The progressive neuronal degeneration in the cortical regions critical for face recognition (viz., right infero-temporal areas) presented us with the opportunity to check Burton et al.'s (1991) and Farah et al.'s (1993) hypothesis on the dissociation between overt and covert face recognition in a neuropsychological condition which, however, is neurologically and cognitively different from that of focal "associative prosopagnosia". Covert person recognition starting from overtly unrecognised faces was assessed by means of learning tasks of face/name association involving celebrities. It was assumed that some unconsciously spared information would selectively enhance the relearning rates when famous faces were paired with their true names. In fact, the true-name advantage (i.e., selective saving for experimental relearning of true name pairings) reached significance at first assessment, carried out five years from clinical onset. Effect faded away two and three years later on, thus abolishing the overt/covert dissociation in face recognition. These findings support Burton et al.'s (1991) and Farah et al.'s (1993) hypothesis of covert face recognition as the consequence of partial and incomplete activation of person semantics, due, in the present case, to the impoverishment of Gentileschi et al.'s (2001) "exemplar semantics" storehouse. Moreover, it turned out that covert recognition does not imply a different learning slope, but an overall different level of the learning profile.}, } @article {pmid12627750, year = {2003}, author = {Schweinberger, SR and Burton, AM}, title = {Covert recognition and the neural system for face processing.}, journal = {Cortex; a journal devoted to the study of the nervous system and behavior}, volume = {39}, number = {1}, pages = {9-30}, doi = {10.1016/s0010-9452(08)70071-6}, pmid = {12627750}, issn = {0010-9452}, mesh = {Brain/*physiology ; *Face ; Humans ; Models, Psychological ; Pattern Recognition, Visual/*physiology ; Prosopagnosia/classification/etiology/psychology ; }, abstract = {In this viewpoint, we discuss the new evidence on covert face recognition in prosopagnosia presented by Bobes et al. (2003, this issue) and by Sperber and Spinnler (2003, this issue). Contrary to earlier hypotheses, both papers agree that covert and overt face recognition are based on the same mechanism. In line with this suggestion, an analysis of reported cases with prosopagnosia indicates that a degree of successful encoding of facial representations is a prerequisite for covert recognition to occur. While we agree with this general conclusion as far as Bobes et al.'s and Sperber and Spinnler's data are concerned, we also discuss evidence for a dissociation between different measures of covert recognition. Specifically, studies in patients with Capgras delusion and patients with prosopagnosia suggest that skin conductance and behavioural indexes of covert face recognition are mediated by partially different mechanisms. We also discuss implications of the new data for models of normal face recognition that have been successful in simulating covert recognition phenomena (e.g., Young and Burton, 1999, and O'Reilly et al., 1999). Finally, in reviewing recent neurophysiological and brain imaging evidence concerning the neural system for face processing, we argue that the relationship between ERP components (specifically, N170, N250r, and N400) and different cognitive processes in face recognition is beginning to emerge.}, } @article {pmid12617266, year = {2003}, author = {Kalanie, H and Gharagozli, K and Kalanie, AR}, title = {Multiple sclerosis: report on 200 cases from Iran.}, journal = {Multiple sclerosis (Houndmills, Basingstoke, England)}, volume = {9}, number = {1}, pages = {36-38}, doi = {10.1191/1352458503ms887oa}, pmid = {12617266}, issn = {1352-4585}, mesh = {Adult ; Age Distribution ; Age of Onset ; Disability Evaluation ; Female ; Humans ; Iran/epidemiology ; Male ; Middle Aged ; Multiple Sclerosis, Chronic Progressive/*epidemiology/pathology ; Multiple Sclerosis, Relapsing-Remitting/*epidemiology/pathology ; Pyramidal Tracts/pathology ; Sex Distribution ; }, abstract = {Clinical findings of 200 patients in Iran with definite multiple sclerosis (MS) according to Poser et al.'s criteria and positive findings on magnetic resonance imaging (MRI) have been reviewed. The clinical course was relapsing-remitting (RR) for 88%, primary progressive (PP) for 7% and secondary progressive (SP) for 5% of cases. The mean age of onset was 27 +/- 7.4 years for the whole group and 37.1 +/- 8.8 years for PPMS. The gender ratio was 2.5:1 female:male. Involvement of the pyramidal system was the most common mode of presentation. Five per cent of patients had positive family history for the disease, 14% of patients had benign MS and 12% with disease duration longer than five years had an Expanded Disability Status Scale < or = 2. The optico-spinal form was not a common form of presentation in the group.}, } @article {pmid12616575, year = {2003}, author = {Dearolf, JL}, title = {Diaphragm muscle development in bottlenose dolphins (Tursiops truncatus).}, journal = {Journal of morphology}, volume = {256}, number = {1}, pages = {79-88}, doi = {10.1002/jmor.10077}, pmid = {12616575}, issn = {0362-2525}, mesh = {Animals ; Animals, Newborn/growth & development/metabolism ; Diaphragm/enzymology/*growth & development/metabolism ; Dolphins/*growth & development ; Electrophoresis ; Histocytochemistry ; Immunohistochemistry ; Myosin Heavy Chains/metabolism ; Protein Isoforms/metabolism ; }, abstract = {Being born directly into the aquatic environment creates unique challenges for the breathing muscles of neonatal cetaceans. Not only must these muscles be active at the instant of birth to ventilate the lungs, but their activities must also be coordinated with those of the locomotor muscles such that breathing takes place only at the water's surface. At least one major locomotory muscle of bottlenose dolphins (Tursiops truncatus) has been demonstrated to be well developed and, therefore, able to power the neonatal dolphin's early movements (Dearolf et al. [2000] J Morphol 244:203-215). Thus, because of the demands for coordinated behavior with the locomotor muscles, it is hypothesized that the breathing muscles of bottlenose dolphins, represented in this study by the diaphragm, will also demonstrate adult morphology at birth. However, histochemical and biochemical analyses demonstrate that neonatal dolphins have immature diaphragms, with only 52% of the adult slow fiber-type profile (neonates: 34% slow-twitch fibers; adults: 66% slow-twitch fibers). The developmental state of the dolphin diaphragm is compared to those of other neonatal mammals, using a muscle development index (% slow-twitch fibers in neonatal muscle / % slow-twitch fibers in adult muscle). Fiber-type profiles reported in the literature are used to calculate index values for the diaphragms of altricial rats, rabbits, and cats, intermediate baboons and humans, and precocial sheep and horses. The dolphin is not unique in having an immature diaphragm at birth; however, there is a positive relationship between the developmental state of the diaphragm and the overall developmental state of the neonate. The presence of type IIc ("undifferentiated") fibers in the diaphragms of altricial developers (e.g., rats, rabbits, and cats) is correlated with the slow contraction speeds recorded from their diaphragms. The diaphragms of neonatal horses and dolphins express little to no type IIc fibers and, thus, may have the ability to contract at the speeds required for their increased ventilation rates. These results lead to the modification of the criterion for evaluating the developmental state of a muscle at birth. Thus, the developmental state of a neonatal muscle should be based on both its value of Dearolf et al.'s (2000) developmental index, as well as the percentage of type IIc fibers found in that muscle.}, } @article {pmid12581994, year = {2003}, author = {Burdorf, A and Van Tongeren, M}, title = {Commentary: variability in workplace exposures and the design of efficient measurement and control strategies.}, journal = {The Annals of occupational hygiene}, volume = {47}, number = {2}, pages = {95-99}, doi = {10.1093/annhyg/meg021}, pmid = {12581994}, issn = {0003-4878}, mesh = {Air Pollutants, Occupational/history ; Chemical Industry/history ; Food-Processing Industry/history ; History, 20th Century ; Humans ; Metallurgy/history ; Netherlands ; Occupational Exposure/history ; Occupational Health/*history ; United Kingdom ; }, abstract = {Kromhout et al.'s (1993) well-cited publication presented detailed information on statistical procedures to estimate the magnitude of exposure variability within and between workers, drawing from a large database on chemical exposures throughout industry. It convincingly demonstrated that the construct of homogeneous exposure groups often does not hold true and suggested ways to improve measurement strategies. The authors hit a rich vein of research, and many publications, not at least by the authors themselves, followed in the decade after publication. In recent years the principles of estimating the variation in exposure have been applied in new methods for optimization of sampling strategies, for compliance testing, for quantifying exposures in epidemiologic studies, and for identifying important sources of emissions and suggesting strategies for controlling exposures. Many occupational hygienists across the globe have adopted these new methods as powerful tools in their exposure assessment strategies.}, } @article {pmid12554449, year = {2002}, author = {Savolainen, V and Heard, SB and Powell, MP and Davies, TJ and Mooers, AØ}, title = {Is cladogenesis heritable?.}, journal = {Systematic biology}, volume = {51}, number = {6}, pages = {835-843}, doi = {10.1080/10635150290102537}, pmid = {12554449}, issn = {1063-5157}, mesh = {Animals ; *Biological Evolution ; Birds ; Genes, Bacterial ; Genes, Fungal ; Genes, Plant ; Insecta/genetics ; Likelihood Functions ; Models, Statistical ; *Phylogeny ; Random Allocation ; }, abstract = {The heritability of speciation rates and extinction risks is a crucial parameter in models of macroevolution, but little direct evidence has been available to assess the occurrence, strength, or generality of this heritability. We tested for heritability using correlations between ancestral and descendent branch lengths in phylogenetic trees, an approach first applied to a bird phylogeny by Harvey et al. (1991, pages 123-137 in Genes in ecology [R. J. Berry et al., eds.], Blackwell Scientific, Oxford). We applied Harvey et al.'s test to some of the largest DNA sequence-based phylogenetic analyses published to date for plants, insects, fungi, and bacteria. If one of two parent lineages splits first and if this is the case for any heritable reason, then on average we expect its daughter lineages to also split first. We also used a randomization procedure to assess significance of branch length heritability. Using maximum parsimony and maximum likelihood branch lengths and trees made ultrametric after nonparametric rate smoothing or by enforcing a molecular clock, we found a pattern for most clades consistent with heritable net cladogenesis. Heritability of cladogenesis may be a general phenomenon, detectable across a large number of lineages and a broad range of taxa.}, } @article {pmid12553516, year = {2002}, author = {Schneider, W and Csepan, R and Kasparek, M and Pinggera, O and Knahr, K}, title = {Intra- and interobserver repeatability of radiographic measurements in hallux surgery: improvement and validation of a method.}, journal = {Acta orthopaedica Scandinavica}, volume = {73}, number = {6}, pages = {670-673}, doi = {10.1080/000164702321039651}, pmid = {12553516}, issn = {0001-6470}, mesh = {Clinical Competence/standards/statistics & numerical data ; Hallux/*diagnostic imaging/*surgery ; Hallux Valgus/*diagnostic imaging/*surgery ; Humans ; Metatarsophalangeal Joint/*diagnostic imaging/*surgery ; *Observer Variation ; Osteotomy ; Practice Guidelines as Topic/*standards ; Radiography ; Random Allocation ; *Reproducibility of Results ; Tarsal Joints/*diagnostic imaging/*surgery ; }, abstract = {To test the hypothesis that the reproducibility of radiographic measurements of the first metatarsophalangeal angle and the intermetatarsal angle I-II can be increased by exact guidelines, we calculated the intra- and interobserver reliability of both methods. 4 independent observers (2 senior residents and 2 orthopedic trainees) evaluated 50 pre- and 50 postoperative plain dorsoplantar radiographs with their method of preference and then with Mitchell et al.'s method (1958). The mean intraobserver coefficient of repeatability for the metatarsophalangeal angle improved from 5.9 degrees to 4.2 degrees and for the intermetatarsal angle I-II, from 4.4 degrees to 2.8 degrees. The interobserver coefficient of repeatability improved from 6.5 degrees to 5.0 degrees for the metatarsophalangeal angle, and from 4.9 degrees to 3.6 degrees for the intermetatarsal angle I-II. This improvement in measurement accuracy was more marked for postoperative measurements, due to deformation of the metatarsal after the osteotomy which made it more difficult to find the longitudinal axis of the metatarsal. The improvements in the accuracy of measurements were also greater in the two inexperienced observers, since their measurements differed more when they had no exact guidelines for their drawings.}, } @article {pmid12542314, year = {2003}, author = {Zagers, NP and Berendschot, TT and van Norren, D}, title = {Wavelength dependence of reflectometric cone photoreceptor directionality.}, journal = {Journal of the Optical Society of America. A, Optics, image science, and vision}, volume = {20}, number = {1}, pages = {18-23}, doi = {10.1364/josaa.20.000018}, pmid = {12542314}, issn = {1084-7529}, mesh = {Humans ; *Light ; *Models, Biological ; Psychophysics/methods ; Pupil/radiation effects ; Retinal Cone Photoreceptor Cells/*physiology/*radiation effects ; Scattering, Radiation ; }, abstract = {We present evidence for the wavelength dependence of the directionality of light reflected from cone receptor cells (optical Stiles-Crawford effect): Blue light is more directional than red. According to the waveguide-scattering model of Marcos et al. [J. Opt. Soc. Am. A 15, 2012 (1998)], directionality is the sum of a waveguide component and a scattering component. The latter is proportional to 1 over wavelength squared, and it is related to the row-to-row spacing of the cone lattice. Our results allow a firm confirmation of Marcos et al.'s theory. For a 1.9-deg foveal area, group mean (n = 18) cone spacing was 3.42 microm, in good agreement with anatomical data. Group mean waveguide directionality was 0.077 mm(-2).}, } @article {pmid12542130, year = {2002}, author = {Mackintosh, B and Mathews, A and Holden, E}, title = {Bigger than a breadbox? Attention to distractors may not enhance negative priming.}, journal = {Journal of experimental psychology. Human perception and performance}, volume = {28}, number = {6}, pages = {1323-1329}, doi = {10.1037//0096-1523.28.6.1323}, pmid = {12542130}, issn = {0096-1523}, mesh = {*Affect ; *Attention ; Humans ; Photic Stimulation ; Random Allocation ; Semantics ; Vocabulary ; }, abstract = {In several recent studies, P. A. MacDonald and colleagues (e.g., P. A. MacDonald & S. Joordens, 2000) reported unusually large negative priming effects and claimed that attention to distractors, counter to expectations, served to enhance the magnitude of the effect. In 3 experiments using their novel comparative judgment task, negative priming was assessed using both a control condition based on that of P. A. MacDonald, S. Joordens, and K. N. Seergobin (1999) and one in which control probe items exactly matched those on ignored repetition trials. In MacDonald et al.'s unmatched control condition, participants were faster than on ignored repetition trials, but this difference was reduced or absent when control items were matched. This result led to the conclusion that the apparently large negative priming effect reported by MacDonald and colleagues may be an artifact arising because judgments for a subset of their control trials were relatively easier than for ignored repetition trials.}, } @article {pmid12540622, year = {2003}, author = {Hanley, AJ and Williams, K and Gonzalez, C and D'Agostino, RB and Wagenknecht, LE and Stern, MP and Haffner, SM and , and , and , }, title = {Prediction of type 2 diabetes using simple measures of insulin resistance: combined results from the San Antonio Heart Study, the Mexico City Diabetes Study, and the Insulin Resistance Atherosclerosis Study.}, journal = {Diabetes}, volume = {52}, number = {2}, pages = {463-469}, doi = {10.2337/diabetes.52.2.463}, pmid = {12540622}, issn = {0012-1797}, support = {DK-29867/DK/NIDDK NIH HHS/United States ; R01 58329//PHS HHS/United States ; R01 HL24799/HL/NHLBI NIH HHS/United States ; R01 HL36820/HL/NHLBI NIH HHS/United States ; U01-HL47887/HL/NHLBI NIH HHS/United States ; U01-HL47889/HL/NHLBI NIH HHS/United States ; U01-HL47892/HL/NHLBI NIH HHS/United States ; U01-HL47902/HL/NHLBI NIH HHS/United States ; }, mesh = {Adult ; Area Under Curve ; Black People ; Cohort Studies ; Diabetes Mellitus, Type 2/*epidemiology ; Female ; Follow-Up Studies ; Hispanic or Latino ; Humans ; Incidence ; Insulin/blood ; Insulin Resistance/*physiology ; Male ; Mexico/epidemiology ; Middle Aged ; Predictive Value of Tests ; Prospective Studies ; ROC Curve ; Risk Factors ; Time Factors ; Triglycerides/blood ; United States/epidemiology ; Black or African American ; }, abstract = {To determine and formally compare the ability of simple indexes of insulin resistance (IR) to predict type 2 diabetes, we used combined prospective data from the San Antonio Heart Study, the Mexico City Diabetes Study, and the Insulin Resistance Atherosclerosis Study, which include well-characterized cohorts of non-Hispanic white, African-American, Hispanic American, and Mexican subjects with 5-8 years of follow-up. Poisson regression was used to assess the ability of each candidate index to predict incident diabetes at the follow-up examination (343 of 3,574 subjects developed diabetes). The areas under the receiver operator characteristic (AROC) curves for each index were calculated and statistically compared. In pooled analysis, Gutt et al.'s insulin sensitivity index at 0 and 120 min (ISI(0,120)) displayed the largest AROC (78.5%). This index was significantly more predictive (P < 0.0001) than a large group of indexes (including those by Belfiore, Avignon, Katz, and Stumvoll) that had AROC curves between 66 and 74%. These findings were essentially similar both after adjustment for covariates and when analyses were conducted separately by glucose tolerance status and ethnicity/study subgroups. In conclusion, we found substantial differences between published IR indexes in the prediction of diabetes, with ISI(0,120) consistently showing the strongest prediction. This index may reflect other aspects of diabetes pathogenesis in addition to IR, which might explain its strong predictive abilities despite its moderate correlation with direct measures of IR.}, } @article {pmid12530721, year = {2002}, author = {Bullitt, C and Farber, BA}, title = {Sex differences in the relationship between interpersonal problems and defensive style.}, journal = {Psychological reports}, volume = {91}, number = {3 Pt 1}, pages = {767-768}, doi = {10.2466/pr0.2002.91.3.767}, pmid = {12530721}, issn = {0033-2941}, mesh = {Adult ; *Defense Mechanisms ; Female ; *Gender Identity ; Humans ; Internal-External Control ; *Interpersonal Relations ; Male ; Middle Aged ; Personality Inventory/statistics & numerical data ; Psychometrics ; Reproducibility of Results ; }, abstract = {Horowitz, et al.'s Inventory of Interpersonal Problems and Bond, et al.'s Defensive Style Questionnaire were completed by 42 women and 35 men. Significant correlations emerged between most interpersonal problems and the tendency for both men and women to use immature and intermediate defense mechanisms in both work and intimate relationships. However, women were more likely than men to employ immature defenses when dealing with issues of "control" in intimate relationships while men were more likely to employ intermediate defenses in response to problems with "intimacy" in work relationships. Data support further inquiry into sex differences in interpersonal problems and defensive style.}, } @article {pmid12528723, year = {2002}, author = {Neill, S}, title = {Re: K. Reddy et al.'s case report on a rare case of plasma cell vulvitis (Zoon's vulvitis).}, journal = {Journal of obstetrics and gynaecology : the journal of the Institute of Obstetrics and Gynaecology}, volume = {22}, number = {2}, pages = {230; author reply 230}, pmid = {12528723}, issn = {0144-3615}, mesh = {Diagnosis, Differential ; Female ; Humans ; Lichen Planus/*complications ; *Plasma Cells ; Vulvitis/diagnosis/*etiology ; }, } @article {pmid12528426, year = {2002}, author = {Schlesewsky, M and Bornkessel, I and Meyer, M}, title = {Why a "word order difference" is not always a "word order" difference: a reply to Weyerts, Penke, Münte, Heinze, and Clahsen.}, journal = {Journal of psycholinguistic research}, volume = {31}, number = {5}, pages = {437-445}, pmid = {12528426}, issn = {0090-6905}, mesh = {Evoked Potentials/physiology ; Humans ; Language ; Memory ; *Vocabulary ; }, abstract = {We present evidence that the supposed processing advantage for an SVfinO word order over an SOVfin word order in German argued for by Weyerts, Penke, Münte, Heinze, and Clahsen (2002) is supported by neither experimental nor theoretical evidence. Specifically, we show (a) that the frontocentral negativity for an SOVfin in comparison to an SVfinO word order in Weyerts et al.'s Experiments 2 and 3 is reducible to more general differences in the electrophysiological responses elicited by nouns versus verbs in a sentence context, and (b) that the P600 difference between the two word orders in Experiment 2, as well as the reading time differences in Experiment 1, result from the fact that the two supposedly ungrammatical conditions actually differ in their degree of ill-formedness. We conclude that there is no evidence for a processing disadvantage for SOVfin, thus reconciling Weyerts et al.'s results on German sentence processing with the grammatical regularities of German.}, } @article {pmid12518814, year = {2003}, author = {Zeller, M and Vannatta, K and Schafer, J and Noll, RB}, title = {Behavioral reputation: a cross-age perspective.}, journal = {Developmental psychology}, volume = {39}, number = {1}, pages = {129-139}, doi = {10.1037//0012-1649.39.1.129}, pmid = {12518814}, issn = {0012-1649}, mesh = {Adolescent ; Age Factors ; Child ; Cross-Sectional Studies ; Factor Analysis, Statistical ; Female ; Humans ; Male ; *Peer Group ; *Social Behavior ; *Social Perception ; Surveys and Questionnaires ; }, abstract = {This study examined the measurement of peer perceptions of behavioral reputation within the contexts of elementary, middle, and high school environments (Grades 2-12, N = 2,812) through the systematic evaluation of the psychometric properties of the Revised Class Play (A. S. Masten, P. Morison, & D. S. Pellegrini, 1985). Confirmatory factor analyses demonstrated that the data did not fit A. S. Masten et al.'s original 3-factor structure. Cross-loading of items and different patterns of association between subscales across age groups (elementary, middle, and high school) contributed to the overall poor fit. Exploratory factor analyses revealed an alternative 4-factor structure as a more reliable and valid means of assessing behavioral reputation regardless of the age of the peer group sampled. Both convergent and divergent patterns of associations emerged across developmental levels.}, } @article {pmid12509168, year = {2002}, author = {Shibahara, N and Kondo, T}, title = {Variables affecting naming latency for Japanese Kanji: a re-analysis of Yamazaki, et al. (1997).}, journal = {Perceptual and motor skills}, volume = {95}, number = {3 Pt 1}, pages = {741-745}, doi = {10.2466/pms.2002.95.3.741}, pmid = {12509168}, issn = {0031-5125}, mesh = {Adolescent ; Adult ; Age Factors ; Female ; Humans ; Japan ; *Language ; *Language Development ; Male ; Pattern Recognition, Visual ; Phonetics ; *Reaction Time ; *Reading ; *Speech Perception ; *Verbal Learning ; }, abstract = {Yamazaki, Ellis, Morrison, and Lambon Ralph in 1997 demonstrated that written and spoken age-of-acquisitions had a stronger effect on the naming latency of single Kanji words than any other variable including familiarity. The present study was designed to reanalyze Yamazaki, et al.'s data, using the ratings of written and spoken age-of-acquisitions and visual and auditory familiarities taken from the NTT lexical database. This analysis showed that visual familiarity exerted a stronger independent effect on naming latency than two types of age-of-acquisitions.}, } @article {pmid12500865, year = {2002}, author = {Francis, G and Hermens, F}, title = {Comment on "Competition for consciousness among visual events: the psychophysics of reentrant visual processes" (Di Lollo, Enns, & Rensink, 2000).}, journal = {Journal of experimental psychology. General}, volume = {131}, number = {4}, pages = {590-3; discussion 594-6}, pmid = {12500865}, issn = {0096-3445}, mesh = {*Attention ; *Computer Simulation ; Humans ; Models, Psychological ; *Orientation ; *Pattern Recognition, Visual ; *Perceptual Masking ; Psychophysics ; }, abstract = {V. Di Lolo, J. T. Enns, and R. A. Rensink (2000) reported properties of masking that they claimed were inconsistent with all current models. The current authors show, through computer simulation, that many current models can account for V. Di Lollo et al.'s (2000) data. Although V. Di Lollo et al. (2000) argued that their data could be accounted for only with models that incorporate reentrant processing, the current authors show that reentrant processing is not necessary.}, } @article {pmid12491655, year = {2002}, author = {Reynolds, M and Besner, D}, title = {Neighbourhood density effects in reading aloud: new insights from simulations with the DRC model.}, journal = {Canadian journal of experimental psychology = Revue canadienne de psychologie experimentale}, volume = {56}, number = {4}, pages = {310-318}, doi = {10.1037/h0087407}, pmid = {12491655}, issn = {1196-1961}, mesh = {*Computer Simulation ; Humans ; *Reading ; *Visual Fields ; *Vocabulary ; }, abstract = {A series of nine simulations with the Dual Route Cascaded (DRC) model (Coltheart, Rastle, Perry, Langdon, & Ziegler, 2001) investigated neighbourhood density (N) effects in nonword and word naming. Two main finding emerged from this work. First, when naming nonwords there are two loci for the effect of N in the model, contrary to Coltheart et al.'s single locus explanation of what the model is doing. The early N effect involves interactive activation between the orthographic lexicon and the letter units such that high N facilitates letter identification, which in turn affects the nonlexical route. The late N effect arises from activation in the orthographic lexicon that feeds forward to the phonological lexicon and primes phonemes in the phoneme system. Second, when naming words the presence/absence of an effect of N on the Letter Units through feedback from the lexical level depends on the parameter settings. Implications and suggestions for future directions are made.}, } @article {pmid12491647, year = {2002}, author = {Tuech, JJ and Pessaux, P and Arnaud, JP}, title = {[Discussion about Peschaud et al.'s article: surgical treatment of pancreatic metastasis from kidney cancer].}, journal = {Annales de chirurgie}, volume = {127}, number = {8}, pages = {656-657}, doi = {10.1016/s0003-3944(02)00845-3}, pmid = {12491647}, issn = {0003-3944}, mesh = {Chemotherapy, Adjuvant ; Humans ; Neoplasm Metastasis ; Pancreatic Neoplasms/*secondary/*surgery ; Prognosis ; Radiotherapy, Adjuvant ; Rectal Neoplasms/*pathology ; }, } @article {pmid12483328, year = {2002}, author = {Arslan, H and Gündüz, S and Subaşi, M and Kesemenli, C and Necmioğlu, S}, title = {Frontal cephalometric analysis in the evaluation of facial asymmetry in torticollis, and outcomes of bipolar release in patients over 6 years of age.}, journal = {Archives of orthopaedic and trauma surgery}, volume = {122}, number = {9-10}, pages = {489-493}, doi = {10.1007/s00402-002-0442-3}, pmid = {12483328}, issn = {0936-8051}, mesh = {Adolescent ; Adult ; *Cephalometry ; Child ; Facial Asymmetry/*complications/diagnosis ; Female ; Humans ; Male ; Torticollis/*complications/*surgery ; }, abstract = {BACKGROUND: The aim of this study was to investigate the mid-term results of bipolar release in congenital muscular torticollis patients over 6 years of age, and the efficacy of frontal cephalometric analysis in the determination and follow-up of facial asymmetry.

METHODS: Twelve patients (9 boys, 3 girls) from 7 to 12 years of age were included in the study. Bipolar release was performed, followed by 5-7 days of traction and 3 months of physiotherapy. Posteroanterior cephalometric radiography was performed at the beginning of and after therapy. The postural symmetry angle (PSA) was used to determine the presence and severity of facial asymmetry. A modified version of Lee et al.'s system was used in evaluating the results.

RESULTS: The average follow-up period was 3 years and 5 months. According to the congenital muscular torticollis evaluation system, the outcome was excellent in 2 of the patients, good in 6, fair in 2 and poor in 2. Asymmetry was not severe in all patients at the beginning of therapy according to PSA values, being insignificant in 2, mild in 6, and severe in 4. The PSA results of the last examination indicated that severe facial asymmetry persisted in 3 patients. In 2 of them, PSA values remained within the limits of severe asymmetry despite a slight angular correction.

DISCUSSION: Congenital muscular torticollis patients can benefit from surgical treatment over the age of 6 years. Bipolar release is an adequate and complication-free method. Moreover, PSA may be used as an objective method in the determination and follow-up of facial asymmetry in torticollis patients.}, } @article {pmid12460267, year = {2002}, author = {Dodrill, CB}, title = {Thoughts on Aldenkamp et al.'s article.}, journal = {Epilepsia}, volume = {43}, number = {12}, pages = {1597; author reply 1597-9}, doi = {10.1046/j.1528-1157.2002.331023.x}, pmid = {12460267}, issn = {0013-9580}, mesh = {Anticonvulsants/*pharmacology ; Bias ; Cognition/*drug effects ; Dose-Response Relationship, Drug ; Functional Laterality/drug effects ; Humans ; Lamotrigine ; Neuropsychological Tests/*statistics & numerical data ; Psychomotor Performance/drug effects ; Triazines/*pharmacology ; Valproic Acid/*pharmacology ; }, } @article {pmid12430345, year = {2002}, author = {Combs, A}, title = {Pet therapy and increased socialization among elderly clients.}, journal = {Kentucky nurse}, volume = {50}, number = {4}, pages = {15-16}, pmid = {12430345}, issn = {0742-8367}, abstract = {Churchill et al.'s (1999) study supported the idea that pet therapy increased socialization and decreased agitation among persons with AD. This study could be used to support the group research utilization project on the use of pet therapy to increase socialization. Future research might concentrate on participants with varied ethnic backgrounds and varied clinical diagnoses. Some feasibility issues would be finding dogs or pets properly trained for therapy and finding nurses properly trained on the use of pet therapy.}, } @article {pmid12430344, year = {2002}, author = {Clark, JP}, title = {Impact of a 5-minute scrub on the microbial flora found on artificial, polished, or natural fingernails of operating room personnel.}, journal = {Kentucky nurse}, volume = {50}, number = {4}, pages = {15}, pmid = {12430344}, issn = {0742-8367}, abstract = {Edel et al.'s (1998) study gave support to the idea that fingernail treatments may put patients at increased risk due to the bacteria carried by nurses or other health care providers. The results of this study could be used to support a research utilization project to educate nurses of the increased risk of infecting patients due to fingernail treatments. Feasibility issues include the cost and time to revise hospital policies concerning fingernail treatments and to educate nurses in the workplace. Future research is needed with larger sample sizes and to investigate possible transmission of infectious bacteria to patients.}, } @article {pmid12420991, year = {2002}, author = {Mattes, S and Leuthold, H and Ulrich, R}, title = {Stimulus-response compatibility in intensity-force relations.}, journal = {The Quarterly journal of experimental psychology. A, Human experimental psychology}, volume = {55}, number = {4}, pages = {1175-1191}, doi = {10.1080/02724980244000152}, pmid = {12420991}, issn = {0272-4987}, mesh = {Adult ; *Auditory Perception ; *Conditioning, Classical ; *Feedback ; Female ; Humans ; Male ; Reaction Time ; *Visual Perception ; }, abstract = {Romaiguère, Hasbroucq, Possamaï, and Seal (1993) reported a new compatibility effect from a task that required responses of two different target force levels to stimuli of two different intensities. Reaction times were shorter when high and low stimulus intensities were mapped to strong and weak force presses respectively than when this mapping was reversed. We conducted six experiments to refine the interpretation of this effect. Experiments 1 to 4 demonstrated that the compatibility effect is clearly larger for auditory than for visual stimuli. Experiments 5 and 6 generalized this finding to a task where stimulus intensity was irrelevant. This modality difference refines Romaiguère et al.'s (1993) symbolic coding interpretation by showing that modality-specific codes underlie the intensity-force compatibility effect. Possible accounts in terms of differences in the representational mode and action effects are discussed.}, } @article {pmid12403181, year = {2002}, author = {von Piekartz, HJ}, title = {Mr. von Piekartz questions Dr. Stiesch-Sholtz, et al.'s conclusions in their April 2002 article in Cranio.}, journal = {Cranio : the journal of craniomandibular practice}, volume = {20}, number = {4}, pages = {238-40; author reply 240-1}, pmid = {12403181}, issn = {0886-9634}, mesh = {Facial Pain/therapy ; Humans ; Pain Measurement ; *Physical Therapy Modalities ; Temporomandibular Joint Disorders/*therapy ; }, } @article {pmid12374328, year = {2002}, author = {Geary, DC and Flinn, MV}, title = {Sex differences in behavioral and hormonal response to social threat: commentary on Taylor et al. (2000).}, journal = {Psychological review}, volume = {109}, number = {4}, pages = {745-50; discussion 751-3}, doi = {10.1037/0033-295x.109.4.745}, pmid = {12374328}, issn = {0033-295X}, mesh = {Altruism ; Biological Evolution ; Escape Reaction ; Female ; Humans ; Male ; *Sex ; *Social Behavior ; Stress, Psychological/*physiopathology/*psychology ; }, abstract = {Taylor and colleagues proposed that women uniquely respond to stressors by tending to children and befriending other women rather than by fighting or fleeing (S. E. Taylor et al., 2000). In this article, the authors expand Taylor et al.'s evolutionary frame and incorporate several unique aspects of human social dynamics. First, humans are characterized by extensive paternal investment, and thus men's tending is predicted and observed in some stressful contexts. Second, the dynamics of women's befriending suggest an evolutionary elaboration of the mechanisms that support reciprocal altruism. Third, coalitional male-male competition indicates that men's befriending is a predicted component of their fight-or-flight response. Finally, men's tending should result in the evolution of female-female competition over this form of parental investment.}, } @article {pmid12356267, year = {2002}, author = {Burke, AC and Rosa-Molinar, E}, title = {Starting from fins: parallelism in the evolution of limbs and genitalia. The fin-to-limb transition.}, journal = {Evolution & development}, volume = {4}, number = {5}, pages = {375-377}, doi = {10.1046/j.1525-142x.2002.02024.x}, pmid = {12356267}, issn = {1520-541X}, mesh = {Animals ; *Biological Evolution ; Extremities/*growth & development ; Fishes/genetics/growth & development ; Genitalia/*growth & development ; }, abstract = {The March/April 2002 issue of Evolution and Development focused on three presentations made at the Starting from Fins: Parallelism in the Evolution of Limbs and Genitalia symposium held as part of the 2001 Chicago meeting of the Society of Integrative and Comparative Biology. The intention of the symposium and the publication of the presentations was to extend discussion of the potential and the limits of using serial homologues to understand developmental aspects of morphological evolution. The March/April 2002 issue concentrated on unpaired fin to genitalia transitions. This issue focuses on paired fins to limbs and highlights the need for developmental data to be integrated with data from fossil materal, phylogenetic analysis, and explicitly comparative studies. Coates et al. use phylogenetic methods to explore the limb/fin characters of taxa, but their analysis departs somewhat from the usual in that the reference group for organisms includes sister group taxa not usually considered true tetrapods. They state that including finned taxa from the stem group permits an attempt to distinguish the primitive condition of the characteristics demonstrated by the crown group, that is, "limbed tetrapods." In focusing on limb characters specifically and including aspects of the appendicular girdles, Coates et al. highlight morphological details and trends within a given phylogeny. They also demonstrate the degree of relevance of limb characters during the establishment of lineages and their branching patterns by using only limb characters to generate a tree and use a direct comparison of serial versus special homologies to explore the degree of evolutionary parallelism between fore-and hindlimbs. The preliminary conclusions indicate a high level of independence between the serially homologous fore-and hindlimb. Innes et al. present outcomes from the use of cutting edge molecular genetic approaches to understand developmental aspects of limb morphology. In a manner conceptually similar to Coates et al.'s use of fossil characters, Innes et al. use the serial analysis of gene expression to sort differences from similarities in the gene expression profiles of fore-and hindlimbs of the same embryos. Although these gene expression pattems are likely to reflect the serial homology of the paired limbs, they are silent in terms of our understanding both the profound and subtle differences between fore- and hindlimbs in any given species. Innes et al. point out the volume of data generated by SAGE far exceeds our ability to interpret its biological meaning. The studies presented here and in the March/April issue are excellent examples of the need to interpret complex data in light of collective knowledge of evolutionary history. We hope the insights gained from the symposium and papers contribute to a dialogue on how to integrate different approaches and assist in moving forward the field of Evolution and Development.}, } @article {pmid12294764, year = {1999}, author = {}, title = {African diversity may hold key to human origins, medical questions. Genetic diversity.}, journal = {AIDS weekly plus}, volume = {}, number = {}, pages = {12}, pmid = {12294764}, mesh = {Africa ; Biology ; Demography ; Developing Countries ; Disease ; *Emigration and Immigration ; *Genetic Diseases, Inborn ; Genetics ; *Genetics, Population ; Population ; Population Dynamics ; }, } @article {pmid12294481, year = {1998}, author = {}, title = {International award received recognizing anti-HIV spermicide.}, journal = {AIDS weekly plus}, volume = {}, number = {}, pages = {10}, pmid = {12294481}, mesh = {*Acquired Immunodeficiency Syndrome ; Americas ; *Contraception ; Contraceptive Agents ; Developed Countries ; Disease ; Economics ; Family Planning Services ; *HIV Infections ; Minnesota ; *Nonoxynol ; North America ; *Research ; *Spermatocidal Agents ; Technology ; United States ; Virus Diseases ; }, } @article {pmid12228333, year = {2002}, author = {Hess, CR and Papas, MA and Black, MM}, title = {Resilience among African American adolescent mothers: predictors of positive parenting in early infancy.}, journal = {Journal of pediatric psychology}, volume = {27}, number = {7}, pages = {619-629}, doi = {10.1093/jpepsy/27.7.619}, pmid = {12228333}, issn = {0146-8693}, mesh = {Adolescent ; Black or African American/*psychology ; Female ; Humans ; Infant ; Infant, Newborn ; Intergenerational Relations ; Longitudinal Studies ; Maternal Age ; Mother-Child Relations ; Mothers/*psychology ; Parenting/ethnology/*psychology ; Personal Satisfaction ; Poverty ; *Psychology, Adolescent ; Random Allocation ; Self Concept ; Social Support ; }, abstract = {OBJECTIVE: To use Nath et al.'s (1991) conceptual model of adolescent parenting to examine the relationship between resiliency factors measured shortly after delivery and maternal parenting behavior at 6 months.

METHOD: We recruited 181 first-time, adolescent African American mothers at delivery. Data on resiliency factors (maturity, self-esteem, and mother-grandmother relationships) were collected when infants were 1-4 weeks of age. Data on parental nurturance and parenting satisfaction were examined through observations and self-report at 6 months.

RESULTS: Multiple regression analyses were used to examine the longitudinal impact of resiliency factors on parental nurturance and parenting satisfaction. Maternal maturity, positive self-esteem, and positive adolescent mother-grandmother relationships (characterized by autonomy and mutuality) were associated with better parenting outcomes. Maternal parenting satisfaction was lowest when infants were temperamentally difficult and mothers and grandmothers had a confrontational relationship.

CONCLUSIONS: Longitudinal associations between mother-grandmother relationships at delivery and parental behavior and satisfaction 6 months later may suggest an intergenerational transmission of parenting style. Recommendations are provided for intervention programs to enhance mother-grandmother relationships in contexts where adolescents are required to live with a guardian to receive government assistance.}, } @article {pmid12223118, year = {2002}, author = {Clarkson, R}, title = {IkB kinase alpha: a link in the chain of the mammary cycle.}, journal = {Breast cancer research : BCR}, volume = {4}, number = {5}, pages = {173-175}, pmid = {12223118}, issn = {1465-5411}, mesh = {Animals ; Apoptosis ; Breast/*enzymology ; Breast Neoplasms/metabolism/pathology ; Cell Division ; Epithelial Cells/enzymology ; Female ; Humans ; I-kappa B Kinase ; NF-kappa B/*metabolism ; Protein Serine-Threonine Kinases/*metabolism ; Signal Transduction ; }, abstract = {The transcription factor NF-kappaB exhibits altered activity in some breast cancers but the relevance of this association has not been established. Cao et al.'s elegant study recently published in Cell reveals a NF-kappaB-dependent signalling pathway responsible for epithelial proliferation in the mouse mammary gland. Could this mechanism, rather than prevention of apoptosis, be responsible for the reported association between NF-kappaB and breast cancer? Could the specificity of NF-kappaB modulators of the IkB kinase complex determine the fate of epithelial cells at different stages of mammary development?}, } @article {pmid12219799, year = {2002}, author = {Nosofsky, RM and Zaki, SR}, title = {Exemplar and prototype models revisited: response strategies, selective attention, and stimulus generalization.}, journal = {Journal of experimental psychology. Learning, memory, and cognition}, volume = {28}, number = {5}, pages = {924-940}, pmid = {12219799}, issn = {0278-7393}, support = {R01 MH48494/MH/NIMH NIH HHS/United States ; }, mesh = {*Attention ; Concept Formation ; Discrimination, Psychological ; Female ; Forecasting ; *Generalization, Psychological ; *Generalization, Stimulus ; Humans ; Male ; Mental Processes ; Mental Recall ; *Models, Psychological ; Random Allocation ; Reproducibility of Results ; Transfer, Psychology ; }, abstract = {J. D. Smith and colleagues (J. P. Minda & J. D. Smith, 2001; J. D. Smith & J. P. Minda, 1998,2000; J. D. Smith, M. J. Murray, & J. P. Minda, 1997) presented evidence that they claimed challenged the predictions of exemplar models and that supported prototype models. In the authors' view, this evidence confounded the issue of the nature of the category representation with the type of response rule (probabilistic vs. deterministic) that was used. Also, their designs did not test whether the prototype models correctly predicted generalization performance. The present work demonstrates that an exemplar model that includes a response-scaling mechanism provides a natural account of all of Smith et al.'s experimental results. Furthermore, the exemplar model predicts classification performance better than the prototype models when novel transfer stimuli are included in the experimental designs.}, } @article {pmid12209861, year = {2002}, author = {Snyder, CR and Rand, KL and King, EA and Feldman, DB and Woodward, JT}, title = {"False" hope.}, journal = {Journal of clinical psychology}, volume = {58}, number = {9}, pages = {1003-1022}, doi = {10.1002/jclp.10096}, pmid = {12209861}, issn = {0021-9762}, mesh = {Affect ; *Goals ; Health Status ; Humans ; *Illusions ; Psychological Theory ; }, abstract = {"False" hope is condemned in the literature on the grounds that it reflects the counterproductive use of: (a) expectations based on illusions rather than reality, (b) inappropriate goals, and (c) poor strategies to reach desired goals. Snyder, Harris, et al.'s (1991) hope theory involving self-referential thoughts about finding routes to desired goals (pathways) and the motivation to use those routes (agency) is used as a framework for examining these three criticisms of false hope. It is concluded that the presently available evidence does not support any of the false-hope criticisms. The implications of hope-related issues for the applied clinical arena are discussed.}, } @article {pmid12195794, year = {2002}, author = {Garner, JP and Falcone, C and Wakenell, P and Martin, M and Mench, JA}, title = {Reliability and validity of a modified gait scoring system and its use in assessing tibial dyschondroplasia in broilers.}, journal = {British poultry science}, volume = {43}, number = {3}, pages = {355-363}, doi = {10.1080/00071660120103620}, pmid = {12195794}, issn = {0007-1668}, mesh = {Animals ; *Chickens ; *Gait ; Lameness, Animal/diagnosis ; Male ; Observer Variation ; Osteochondrodysplasias/diagnosis/pathology/physiopathology/*veterinary ; Poultry Diseases/*diagnosis/pathology/physiopathology ; Reproducibility of Results ; Severity of Illness Index ; Tibia ; Videotape Recording ; }, abstract = {1. The gait scoring system for broilers developed by Kestin et al. (Veterinary Record, 131: 190-194, 1992) has been widely used to evaluate leg problems. The many factors and measures associated with this scale have empirically established its external (biological) validity. However, published test-retest (within-observer) reliabilities are poor, and inter-observer reliabilities are unknown. We evaluated several modifications to this scale aimed at improving its objectivity and reliability. 2. Eighteen naïve observers scored a standardised video of birds exhibiting varying degrees of lameness, either using Kestin et al.'s system, or our modified system. 3. Test-retest reliability (0.906) for Kestin et al.'s system was higher than previously reported. Inter-rater reliability was also good (0.892). The modified system offered significantly better test-retest (0.948) and inter-rater reliabilities (0.943), without incurring costs in terms of time taken or difficulty of use. The systems were consistent, assigning individual birds the same score on average. 4. It is concluded that the modified system offers the advantages of reduced error within and between studies. 5. In a second experiment, we used our modified scoring system to examine the relationship between tibial dyschondroplasia (TD) and gait score in 267 selected broilers. 6. Neither the presence nor severity of TD affected gait score, suggesting that, at least in this strain of broilers, other leg problems like slipped tendons or torsional deformities had more influence on gait impairment than did TD.}, } @article {pmid12194826, year = {2002}, author = {Rorden, C and Greene, K and Sasine, G and Baylis, G}, title = {Enhanced tactile performance at the destination of an upcoming saccade.}, journal = {Current biology : CB}, volume = {12}, number = {16}, pages = {1429-1434}, doi = {10.1016/s0960-9822(02)01039-4}, pmid = {12194826}, issn = {0960-9822}, mesh = {*Attention ; Hand ; Humans ; Reaction Time ; Saccades/*physiology ; *Signal Detection, Psychological ; Time Factors ; Touch/*physiology ; Visual Perception ; }, abstract = {Previous work has demonstrated that upcoming saccades influence visual and auditory performance even for stimuli presented before the saccade is executed. These studies suggest a close relationship between saccade generation and visual/auditory attention. Furthermore, they provide support for Rizzolatti et al.'s premotor model of attention, which suggests that the same circuits involved in motor programming are also responsible for shifts in covert orienting (shifting attention without moving the eyes or changing posture). In a series of experiments, we demonstrate that saccade programming also affects tactile perception. Participants made speeded saccades to the left and right side as well as tactile discriminations of up versus down. The first experiment demonstrates that participants were reliably faster at responding to tactile stimuli near the location of upcoming saccades. In our second experiment, we had the subjects cross their hands and demonstrated that the effect occurs in visual space (rather than the early representations of touch). In our third experiment, the tactile events usually occurred on the opposite side of upcoming eye movement. We found that the benefit at the saccade target location vanished, suggesting that this shift is not obligatory but that it may be vetoed on the basis of expectation.}, } @article {pmid12191935, year = {2002}, author = {Trevena, JA and Miller, J}, title = {Cortical movement preparation before and after a conscious decision to move.}, journal = {Consciousness and cognition}, volume = {11}, number = {2}, pages = {162-90; discussion 314-25}, doi = {10.1006/ccog.2002.0548}, pmid = {12191935}, issn = {1053-8100}, mesh = {Cerebral Cortex/*physiology ; Consciousness/*physiology ; Decision Making/*physiology ; Evoked Potentials/physiology ; Humans ; Judgment/physiology ; Movement/*physiology ; Time Factors ; Time Perception ; }, abstract = {The idea that our conscious decisions determine our actions has been challenged by a report suggesting that the brain starts to prepare for a movement before the person concerned has consciously decided to move (Libet, Gleason, Wright, & Pearl, 1983). Libet et al. claimed that their results show that our actions are not consciously initiated. The current article describes two experiments in which we attempted to replicate Libet et al.'s comparison of participants' movement-related brain activity with the reported times of their decisions to move and also the reported times of their decisions of which hand to move. We also looked at the distribution of participants' reports over time to evaluate an alternative explanation of Libet et al.'s (1983) results. Although the Readiness Potential was usually present before all of the decisions to move, consistent with the findings of Keller and Heckhausen (1990) and Libet et al. (1983), we found that many reported decision times were before the onset of the Lateralized Readiness Potential, which measures hand-specific movement preparation. The latter finding is consistent with the conclusion that the LRP always started after the conscious decision to move. We conclude that even though activity related to movement anticipation may be present before a conscious decision to move, the cortical preparation necessary for the movement to happen immediately may not start until after the conscious decision to move.}, } @article {pmid12167298, year = {2002}, author = {McNevin, NH and Wulf, G}, title = {Attentional focus on supra-postural tasks affects postural control.}, journal = {Human movement science}, volume = {21}, number = {2}, pages = {187-202}, doi = {10.1016/s0167-9457(02)00095-7}, pmid = {12167298}, issn = {0167-9457}, mesh = {Adult ; Attention/*physiology ; Female ; Humans ; Male ; Middle Aged ; *Posture ; Psychomotor Performance/physiology ; }, abstract = {We examined whether the attentional focus adopted on a supra-postural task has an influence on postural control. Similar to Riley, Stoffregen, Grocki, and Turvey (Human Movement Science 18 (1999) 795), participants were instructed to stand still while lightly touching a loosely hanging sheet with their fingertips. However, instructions varied slightly under two conditions: Participants were either asked to minimize movements of the finger (internal focus) or to minimize movements of the sheet (external focus). In contrast to Riley et al.'s findings, both touch conditions resulted in increased postural sway, compared to a baseline condition (no touch). However, in line with previous findings (e.g., Wulf, McNevin, & Shea, Quarterly Journal of Experimental Psychology 54A (2001) 1143), frequency of responding (fast Fourier transformation) was greater under the external focus condition, compared to both internal focus and baseline conditions. The findings indicate improved static balance responses under external focus conditions and compromised static balance response under internal focus conditions.}, } @article {pmid12150260, year = {2002}, author = {Satloff, D}, title = {Dr. Satloff expands on Bayar, et al.'s April article in CRANIO.}, journal = {Cranio : the journal of craniomandibular practice}, volume = {20}, number = {3}, pages = {154}, pmid = {12150260}, issn = {0886-9634}, mesh = {Arthritis, Rheumatoid/*diagnosis ; Diagnostic Imaging ; Humans ; Temporomandibular Joint Disorders/*diagnosis ; Tomography, X-Ray ; }, } @article {pmid12150259, year = {2002}, author = {Gassner, RJ and Agarwal, S}, title = {Drs. Gassner and Agarwal respond to Maloney, et al.'s article in the January 2002 issue of CRANIO.}, journal = {Cranio : the journal of craniomandibular practice}, volume = {20}, number = {3}, pages = {152-153}, pmid = {12150259}, issn = {0886-9634}, support = {R01 DE015399/DE/NIDCR NIH HHS/United States ; AT00646/AT/NCCIH NIH HHS/United States ; DE12976-01/DE/NIDCR NIH HHS/United States ; DE13799/DE/NIDCR NIH HHS/United States ; }, mesh = {Animals ; Cartilage, Articular/physiopathology ; Chondrocytes/physiology ; Collagen/physiology ; Extracellular Matrix/physiology ; Humans ; Inflammation Mediators/metabolism ; Interleukin-1/biosynthesis ; *Motion Therapy, Continuous Passive ; Rabbits ; Stress, Mechanical ; Temporomandibular Joint Disorders/physiopathology/*therapy ; Tumor Necrosis Factor-alpha/biosynthesis ; }, } @article {pmid12148161, year = {2002}, author = {Au-Yeung, J and Howell, P}, title = {Non-word reading, lexical retrieval and stuttering: comments on Packman, Onslow, Coombes and Goodwin (2001).}, journal = {Clinical linguistics & phonetics}, volume = {16}, number = {4}, pages = {287-293}, pmid = {12148161}, issn = {0269-9206}, support = {072639/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Humans ; Phonetics ; *Reading ; *Stuttering ; *Vocabulary ; }, abstract = {A recent study by Packman, Onslow, Coombes and Goodwin (2001) employed a non-word-reading paradigm to test the contribution of the lexical retrieval process to stuttering. They consider that, with this material, the lexical retrieval process could not contribute to stuttering and that either anxiety and/or the motor demand of reading are the governing factors. This paper will discuss possible processes underlying non-word reading and it argues that the conclusion arrived at by Packman et al. does not stand up to close scrutiny. In their introduction, the authors acknowledge that the lexicalization process involves retrieval and encoding of words. In a non-word-reading task, the word retrieval component is eliminated. The possibility that the encoding component of the lexicalization process leads to stuttering is, however, completely ignored by the authors when they attribute stuttering to motor demands. As theories put forward by Postma and Kolk (the Covert Repair Hypothesis, 1993) and Howell and Au-Yeung (the EXPLAN theory, 2002) argue heavily for the role of the phonological encoding processes in stuttering, Packman et al.'s work does not evaluate such theories. Theoretical issues aside, Packman et al.'s arguments about reading rate and stuttering rate based on reading time is also questionable.}, } @article {pmid12132907, year = {2002}, author = {Daniel, S and Hoffman, DM}, title = {Synthesis and structures of aluminum alkanethiolate complexes.}, journal = {Inorganic chemistry}, volume = {41}, number = {15}, pages = {3843-3849}, doi = {10.1021/ic011257g}, pmid = {12132907}, issn = {0020-1669}, abstract = {The homoleptic aluminum thiolate complex [Al(mu-S-t-Bu)(S-t-Bu)(2)](2) was prepared by reacting AlBr(3) with NaS-t-Bu while the analogous 2-propanethiolate complex [Al(mu-S-i-Pr)(S-i-Pr)(2)](2) was synthesized by reacting AlH(3)(OEt(2)) with i-PrSH. In the solid state, the dimers have tetrahedral Al atoms and anti-Al(mu-SR)(2)Al four-member rings. The attempted synthesis of [Al(mu-S-t-Bu)(S-t-Bu)(2)](2) by reacting Al(N-i-Pr(2))(3) with t-BuSH in THF solvent yielded the thermally stable THF adduct Al(S-t-Bu)(3)(THF). The same reaction in diethyl ether solvent produced a mixture of [Al(mu-mgr;-S-t-Bu)(S-t-Bu)(2)](2) and the salt [i-Pr(2)NH(2)][Al(S-t-Bu)(4)]. In the solid-state structure of the salt, the anion [Al(S-t-Bu)(4)](-) has a distorted tetrahedral geometry. Reactions of [Al(NMe(2))(3)](2) and AlH(3)(NMe(2)Et) with the alkanethiols yielded stable amine adducts Al(SR)(3)(R'NMe(2)) (R = i-Pr or t-Bu; R' = H or Et). The ligand adducts Al(S-i-Pr)(3)(HNMe(2)) and Al(S-t-Bu)(3)(THF) have distorted trigonal pyramidal geometries in the solid state. Three of the new compounds, [Al(mu-S-i-Pr)(S-i-Pr)(2)](2) and Al(SR)(3)(HNMe(2)) (R = i-Pr or t-Bu), are viable precursor candidates for the chemical vapor deposition of aluminum sulfide films because they are thermally stable, volatile liquids at moderate temperatures.}, } @article {pmid12111729, year = {2002}, author = {Gibson, G}, title = {A genetic attack on the defense complex.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {24}, number = {6}, pages = {487-489}, doi = {10.1002/bies.10104}, pmid = {12111729}, issn = {0265-9247}, mesh = {Animals ; *Chromosome Mapping ; Fishes ; Genetic Variation ; Genome ; Microsatellite Repeats/*genetics ; Quantitative Trait, Heritable ; }, abstract = {An increasing number of "non-model" organisms are becoming accessible to genetic analysis in the field, as evolutionary biologists develop dense molecular genetic maps. Peichel et al.'s recent study(1) provides a microsatellite-based map for threespine stickleback fish (Gasterosteus aculeatus), and the first evidence for QTL affecting feeding morphology and defensive armor. This species has undergone rapid and parallel morphological and behavioral evolution, and there is now hope that some of the genes responsible for the divergence may soon be identified.}, } @article {pmid12102117, year = {2002}, author = {Possamaï, CA and Burle, B and Osma, A and Hasbroucq, T}, title = {Partial advance information, number of alternatives, and motor processes: an electromyographic study.}, journal = {Acta psychologica}, volume = {111}, number = {1}, pages = {125-139}, doi = {10.1016/s0001-6918(02)00019-7}, pmid = {12102117}, issn = {0001-6918}, support = {NS37528/NS/NINDS NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Analysis of Variance ; Cues ; Electromyography ; Female ; Hand/physiology ; Humans ; Male ; Mental Processes/*physiology ; Middle Aged ; Motor Skills/*physiology ; Movement/physiology ; Reaction Time ; }, abstract = {We present evidence that advance information reducing the number of stimulus-response alternatives in a choice reaction time (RT) task can shorten the very latest motoric stages of RT. Effects of such advance information on late stages of RT have been demonstrated recently by Osman, Moore, and Ulrich (Acta Psychol. 90 (1995) 111), Leuthold, Sommer, and Ulrich (J. Exp. Psychol: Gen. 125 (1996) 307), Müller-Gethmann, Rinkenauer, Stahl, and Ulrich (Psychophysiology 37 (2000) 507). These studies found that advance information shortens the portion of the RT interval following onset of a movement-related brain potential (lateralized readiness potential). Osman et al. and Müller-Gethmann et al. also examined the portion of the RT interval following the start of electromyographic (EMG) activity and found no effect of advance information. Based on Osman et al.'s null result, Leuthold et al. speculated that advance information may shorten only the RT stages preceding EMG activity. This conclusion, however, is questionable because of limitations in the EMG measures employed by both Osman et al. and Müller-Gethmann et al. We have reanalyzed the results of a previously reported experiment (Acta Psychol. 101 (1999) 243) to show that advance information can in fact affect the rate of recruitment of motor units in the prime mover of the responding limb.}, } @article {pmid12081457, year = {2002}, author = {Bryant, P}, title = {It doesn't matter whether onset and rime predicts reading better than phoneme awareness does or vice versa.}, journal = {Journal of experimental child psychology}, volume = {82}, number = {1}, pages = {41-6; discussion 58-64}, doi = {10.1006/jecp.2002.2672}, pmid = {12081457}, issn = {0022-0965}, mesh = {*Awareness ; Child ; Child, Preschool ; Female ; Humans ; Male ; *Phonetics ; Prognosis ; *Reading ; *Semantics ; }, abstract = {Hulme et al. argue against our hypothesis that there are two routes from onset and rime awareness to reading: an indirect route whereby onset-rime awareness feeds into the development of phoneme awareness which in turn affects children's reading, and a direct route by which onset-rime awareness makes an independent contribution to children's reading. The evidence that Hulme et al. present against this hypothesis is not convincing, partly because our hypothesis actually predicts most of their results and partly because of weaknesses in the design of Hulme et al.'s study and in the unusual procedures that they employed.}, } @article {pmid12059010, year = {2002}, author = {Jaffrin, MY and Fenech, M and de Fremont, JF and Tolani, M}, title = {Continuous monitoring of plasma, interstitial, and intracellular fluid volumes in dialyzed patients by bioimpedance and hematocrit measurements.}, journal = {ASAIO journal (American Society for Artificial Internal Organs : 1992)}, volume = {48}, number = {3}, pages = {326-333}, doi = {10.1097/00002480-200205000-00021}, pmid = {12059010}, issn = {1058-2916}, mesh = {Adult ; Aged ; Body Water/metabolism ; Electric Impedance ; Extracellular Space/*metabolism ; Female ; *Hematocrit ; Humans ; Intracellular Fluid/*metabolism ; Male ; Middle Aged ; *Plasma Volume ; *Renal Dialysis ; }, abstract = {Bioimpedance spectroscopy (BIS) permits evaluation of extra- and intracellular fluid volumes in patients. We wished to examine whether this technique, used in combination with hematocrit measurement, can reliably monitor fluid transfers during dialysis. Ankle to wrist BIS measurements were collected during 21 dialysis runs while hematocrit was continuously monitored in the blood line by an optical device. Extracellular (ECW) and intracellular (ICW) water volumes were calculated using Hanai's electrical model of suspensions. Plasma volume variations were calculated from hematocrit, and changes in interstitial volume were calculated as the difference between ECW and plasma volume changes. Because accuracy of ICW was too low, changes in ICW were calculated as the difference between ultrafiltered volume and ECW changes. Total body water (TBW) volumes calculated pre- and postdialysis were, respectively, 3.25+/-3.2 and 1.95+/-2.5 liters lower on average than TBW given by Watson et al.'s correlation. Average decreases in fluid compartments expressed as percentage of ultrafiltered volume were as follows: plasma, 18%; interstitial, 28%, and ICW, 54%. When the ultrafiltered volume was increased in a patient in successive runs, the relative contributions of ICW and interstitial fluid were augmented so as to reduce the relative drop in plasma volume.}, } @article {pmid12035619, year = {2001}, author = {Chiappero, MB and Gardenal, CN}, title = {Inheritance of random amplified polymorphic DNA (RAPD-PCR) markers and their use in population genetic studies of Calomys musculinus (Rodentia, Muridae), the reservoir of Argentine hemorrhagic fever.}, journal = {Hereditas}, volume = {135}, number = {1}, pages = {85-93}, doi = {10.1111/j.1601-5223.2001.t01-1-00085.x}, pmid = {12035619}, issn = {0018-0661}, mesh = {Alleles ; Animals ; Crosses, Genetic ; Female ; *Genetic Markers ; Genetics, Population ; Junin virus/metabolism ; Male ; Phenotype ; Phylogeny ; Polymorphism, Genetic ; Random Amplified Polymorphic DNA Technique/*methods ; Rodentia ; }, abstract = {In order to assess the reliability of RAPD markers in the estimation of the genetic structure of natural populations of the murid rodent Calomys musculinus (reservoir of Junin virus, ethiological agent of Argentine Hemorrhagic Fever), we have analyzed the heritability of RAPD bands in 10 parents and their offspring (33 individuals). Fourteen out of a total of 119 bands obtained were absent in the parental patterns, but consistently amplified in offspring from some families. These bands can be eliminated from analyses. Overall degree of band sharing between individuals, including non-parental bands, correctly grouped members of a family in the same cluster in a UPGMA tree, with a high bootstrap percentage. Results support the usefulness of RAPDs as hereditable markers. One hundred polymorphic RAPD loci were identified in three natural populations of C. musculinus. Mean expected heterozygosity in three natural populations ranged from 0.206 to 0.220. Allele frequency based and phenotype based measures of genetic differentiation among natural populations of C. musculinus gave similar results (Weir and Cockerham's theta = 0.133; Excoffier et al.'s phi = 0.127). These values were considerably higher than those found previously using allozymes as genetic markers, and are compatible with moderate to low levels of gene flow among populations.}, } @article {pmid12024075, year = {2002}, author = {Akça, O and Doufas, AG and Sessler, DI}, title = {Use of selective opiate receptor inhibitors to prevent postoperative ileus.}, journal = {Minerva anestesiologica}, volume = {68}, number = {4}, pages = {162-165}, pmid = {12024075}, issn = {0375-9393}, support = {GM49670/GM/NIGMS NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Aged ; Humans ; Intestinal Obstruction/*prevention & control ; Middle Aged ; *Narcotic Antagonists ; Piperidines/*therapeutic use ; Postoperative Complications/*prevention & control ; Postoperative Nausea and Vomiting/*prevention & control ; Randomized Controlled Trials as Topic ; }, abstract = {Ileus is a common postoperative complication after major abdominal surgery. Surgical manipulation of the bowel and stimulation of opiod receptor are the main causes of ileus. An investigational drug (ADL 8-2698, Alvinopam) a selective opioid antagonist with a very low oral absorption was recently introduced to clinical medicine. Unlike other opioid antagonist its activity is restricted to GI tract, it is potent, has a long duration of action, is orally effective, does not readily cross the blood-brain barrier even after intravenous administration in animals. Two randomized controlled clinical studies tested its effects in humans. Liu et al.'s study confirmed peripheral restriction of ADL 8-2698 by its lack of central effect on morphine analgesia and pupil miosis. They also showed that ADL 8-2698 prevents increases in gastrointestinal transit time. Taguchi et al. concluded that high dose (6 mg) of ADL 8-2698 archived fast recovery of gastrointestinal function, without antagonising analgesic efficacy of systemic opioid. In summary, selective inhibition of gastrointestinal opioid receptor by a peripherally restricted oral antagonist speeds recovery of bowel function, shortens times of hospitalization and preserves the analgesic effects of opiods.}, } @article {pmid12002832, year = {2002}, author = {Melis, M}, title = {Dr. Melis comments on Miralles, et al.'s article in the January 2002 issue of CRANIO. The relationship between occlusion and the cranio-cervical complex.}, journal = {Cranio : the journal of craniomandibular practice}, volume = {20}, number = {2}, pages = {79}, pmid = {12002832}, issn = {0886-9634}, mesh = {Humans ; Neck Muscles/*physiology ; *Vertical Dimension ; }, } @article {pmid11999337, year = {2002}, author = {Willems, S and Adam, S and Van der Linden, M}, title = {Normal mere exposure effect with impaired recognition in Alzheimer's disease.}, journal = {Cortex; a journal devoted to the study of the nervous system and behavior}, volume = {38}, number = {1}, pages = {77-86}, doi = {10.1016/s0010-9452(08)70640-3}, pmid = {11999337}, issn = {0010-9452}, mesh = {Aged ; Alzheimer Disease/*physiopathology ; Brain/*physiopathology ; Cues ; *Facial Expression ; Female ; Humans ; Male ; Memory Disorders/*diagnosis ; Photic Stimulation ; Recognition, Psychology/*physiology ; Time Factors ; *Visual Perception ; }, abstract = {We investigated the mere exposure effect and the explicit memory in Alzheimer's disease (AD) patients and elderly control subjects, using unfamiliar faces. During the exposure phase, the subjects estimated the age of briefly flashed faces. The mere exposure effect was examined by presenting pairs of faces (old and new) and asking participants to select the face they liked. The participants were then presented with a forced-choice explicit recognition task. Controls subjects exhibited above-chance preference and recognition scores for old faces. The AD patients also showed the mere exposure effect but no explicit recognition. These results suggest that the processes involved in the mere exposure effect are preserved in AD patients despite their impaired explicit recognition. The results are discussed in terms of Seamon et al.'s (1995) proposal that processes involved in the mere exposure effect are equivalent to those subserving perceptual priming. These processes would depend on extrastriate areas which are relatively preserved in AD patients.}, } @article {pmid11992662, year = {2002}, author = {Guariglia, C and Piccardi, L and Puglisi Allegra, MC and Traballesi, M}, title = {Is autotopoagnosia real? EC says yes. A case study.}, journal = {Neuropsychologia}, volume = {40}, number = {10}, pages = {1744-1749}, doi = {10.1016/s0028-3932(02)00013-1}, pmid = {11992662}, issn = {0028-3932}, mesh = {Aged ; Agnosia/*diagnostic imaging/etiology/psychology ; *Body Image ; Cerebral Infarction/*complications ; Female ; Functional Laterality ; Humans ; Neuropsychological Tests ; Tomography, X-Ray Computed ; }, abstract = {We report a case of pure autotopagnosia (AT) following a left subcortical vascular accident. The absence of any language disorder, general mental deterioration or other cognitive impairments in this patient allowed an in-depth study of AT. Several tests of body representation and object and animal representation, as well as tests assessing semantic skills were administered to verify current interpretations of AT. Results showed a clear-cut dissociation between defective performances in body representation tests and normal performances on tests involving other kinds of stimuli. The patient's performances were particularly defective on tests relying on visuo-spatial body representation, but her semantic and linguistic knowledge seemed to be spared. This dissociation between different aspects of body representation supports Sirigu et al.'s hypothesis that multiple, partially independent systems are involved in body knowledge. In agreement with this hypothesis, in the present patient AT seems be due to a deficit in a system that processes the structural properties and relative position of single body parts. The present results, reporting the first observation of a subject not affected by any cognitive impairment other than AT, strongly support the existence of a system specifically devoted to body representation.}, } @article {pmid11976012, year = {2002}, author = {Regnicolo, L and Messori, A and Polonara, G and Burroni, E and Perugini, S and Salvolini, U}, title = {MRI assessment of post-traumatic spinal instability.}, journal = {European journal of radiology}, volume = {42}, number = {2}, pages = {154-159}, doi = {10.1016/s0720-048x(02)00041-4}, pmid = {11976012}, issn = {0720-048X}, mesh = {Adolescent ; Adult ; Aged ; Feasibility Studies ; Female ; Humans ; Italy ; *Magnetic Resonance Imaging ; Male ; Middle Aged ; Retrospective Studies ; Spinal Injuries/complications/*diagnosis/pathology ; }, abstract = {The imaging evaluation of patients with spinal trauma has evolved over the past decades, and there has been particular interest in the concept of instability, to predict which a series of criteria have been proposed. We retrospectively evaluated the magnetic resonance imaging (MRI) findings in 50 patients with post-traumatic spinal instability according to Denis's three-column method, Daffner et al.'s radiographic criteria, and Oner et al.'s categorization of MRI findings; additionally, we evaluated the cord, the prevertebral tissue, and the epidural space. We suggest that an integrated panel of MRI information might be standardized in order to provide a more complete evaluation of spinal injury in an individual case and help planning surgical treatment.}, } @article {pmid11969991, year = {1999}, author = {Phan, SE and Li, M and Russel, WB and Zhu, J and Chaikin, PM and Lant, CT}, title = {Linear viscoelasticity of hard sphere colloidal crystals from resonance detected with dynamic light scattering.}, journal = {Physical review. E, Statistical physics, plasmas, fluids, and related interdisciplinary topics}, volume = {60}, number = {2 Pt B}, pages = {1988-1998}, doi = {10.1103/physreve.60.1988}, pmid = {11969991}, issn = {1063-651X}, mesh = {Colloids/*chemistry ; Crystallography/*instrumentation/*methods ; Light ; Models, Chemical ; Pharmaceutical Preparations/chemistry ; Rheology/instrumentation/methods ; Scattering, Radiation ; Stress, Mechanical ; Vibration ; Viscosity ; }, abstract = {We present measurements of the high-frequency shear modulus and dynamic viscosity for nonaqueous hard sphere colloidal crystals both in normal and microgravity environments. All experiments were performed on a multipurpose PHaSE instrument. For the rheological measurements, we detect the resonant response to oscillatory forcing with a dynamic light scattering scheme. The resonant response for colloidal crystals formed in normal and microgravity environments was similar, indicating that the bulk rheological properties are unaffected by differing crystal structure and crystallite size within the experimental error. Our high-frequency shear modulus seems reasonable, lying close to Frenkel and Ladd's predictions [Phys. Rev. Lett. 59, 1169 (1987)] for the static modulus of hard sphere crystals. Our high-frequency dynamic viscosity, on the other hand, seems high, exceeding Shikata and Pearson [J. Rheol. 38, 601 (1994)] and van der Werff et al.'s measurements [Phys. Rev. A 39, 795 (1989)] on the high-frequency dynamic viscosity for metastable fluids. The measurements are in the linear regime for the shear modulus but may not be for the dynamic viscosity as Frith et al. [Powder Technol. 51, 27 (1987)] report that the dynamic viscosity passes through a maximum with strain amplitude.}, } @article {pmid11913031, year = {2002}, author = {Stokes, SF}, title = {Levels of complexity in phonological disorders: evidence from Cantonese.}, journal = {Clinical linguistics & phonetics}, volume = {16}, number = {1}, pages = {35-57}, doi = {10.1080/02699200110101747}, pmid = {11913031}, issn = {0269-9206}, mesh = {Articulation Disorders/*diagnosis ; Child, Preschool ; Humans ; *Language ; Male ; *Phonetics ; Severity of Illness Index ; }, abstract = {Longitudinal data from ten phonologically disordered Cantonese-speaking boys were analysed for distinctive features (manner and place). The children labelled 95 pictures, attempting each initial Cantonese segment at least five times. The applicability of Dinnsen et al.'s implicational hierarchy to this data was examined. Categorization of each child's system according to an implicational hierarchy was successful for nine of the ten children when phonetic inventories were considered. In addition, a phonemic inventory based on Dinnsen et al.'s phonetic inventory captured the system of phonological contrasts used by eight of the ten children. The patterns of the children who did not match the hierarchy were considered deviant rather than delayed. The ability of the hierarchy to predict the route of development in this group of children was also examined. The hierarchies (both phonetic and phonemic) successfully predicted the route of change in these cases. Implications for the use of an implicational hierarchy in phonological assessment and treatment are discussed. Further research on feature-based phonological development, in both typically-developing and disordered phonological systems is required.}, } @article {pmid11904781, year = {2002}, author = {Forrest, GN and Schimpff, SC and Cross, A}, title = {Febrile neutropenia, colony-stimulating factors and therapy: time for a new methodology?.}, journal = {Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer}, volume = {10}, number = {3}, pages = {177-180}, doi = {10.1007/s00520-002-0347-2}, pmid = {11904781}, issn = {0941-4355}, mesh = {Cost-Benefit Analysis ; Fever/*therapy ; Granulocyte Colony-Stimulating Factor/economics/*therapeutic use ; Humans ; Neutropenia/*therapy ; }, abstract = {The utilization of granulocyte colony-stimulating factors (G-CSF) in febrile neutropenia has been controversial for many years. Berghmann et al.'s meta-analysis again demonstrates that G-CSF does not have an impact on mortality in febrile neutropenia, because the depth and duration of neutropenia in the trials are variable. Also, with mortality from febrile neutropenia less than 15%, any further study would require a vast number of patients to demonstrate a difference in mortality. The Elting and Cantor review provides a new paradigm to studies in patients with febrile neutropenia. These authors recognize that cost, quality of life, life-years gained and adverse events experienced with new therapies should be evaluated, in addition to the standard measures of infection resolution and related mortality. Therefore, for the evaluation of new therapeutic interventions, a consensus on stratified risk factors or the use of an already established model could provide end-points with comparable measurements.}, } @article {pmid11903898, year = {2001}, author = {Eldridge, MD and Kinnear, JE and Onus, ML}, title = {Source population of dispersing rock-wallabies (Petrogale lateralis) identified by assignment tests on multilocus genotypic data.}, journal = {Molecular ecology}, volume = {10}, number = {12}, pages = {2867-2876}, doi = {10.1046/j.0962-1083.2001.01403.x}, pmid = {11903898}, issn = {0962-1083}, mesh = {Animals ; Bayes Theorem ; Cluster Analysis ; DNA/chemistry ; *Ecology ; Genetic Variation ; *Genetics, Population ; Genotype ; Macropodidae/classification/*genetics ; Microsatellite Repeats/genetics ; Population Dynamics ; Western Australia ; }, abstract = {The ability to confidently identify or exclude a population as the source of an individual has numerous powerful applications in molecular ecology. Several alternative assignment methods have recently been developed and are yet to be fully evaluated with empirical data. In this study we tested the efficacy of different assignment methods by using a translocated rock-wallaby (Petrogale lateralis) population, of known provenance. Specimens from the translocated population (n = 43), its known source population (n = 30) and four other nearby populations (n = 19-32) were genotyped for 11 polymorphic microsatellite loci. The results identified Bayesian clustering, frequency and Bayesian methods as the most consistent and accurate, correctly assigning 93-100% of individuals up to a significance threshold of P = 0.01. Performance was variable among the distance-based methods, with the Cavalli-Sforza and Edwards chord distance performing best, whereas Goldstein et al.'s (deltamu)2 consistently performed poorly. Using Bayesian clustering, frequency and Bayesian methods we then attempted to determine the source of rock-wallabies which have recently recolonized an outcrop (Gardners) 8 km from the nearest rock-wallaby population. Results indicate that the population at Gardners originated via a recent dispersal event from the eastern end of Mt. Caroline. This is only the second published record of dispersal by rock-wallabies between habitat patches and is the longest movement recorded to date. Molecular techniques and methods of analysis are now available to allow detailed studies of dispersal in rock-wallabies and should also be possible for many other taxa.}, } @article {pmid11869744, year = {2002}, author = {García-Campayo, J and Claraco, LM and Sanz-Carrillo, C and Arévalo, E and Monton, C}, title = {Assessment of a pilot course on the management of somatization disorder for family doctors.}, journal = {General hospital psychiatry}, volume = {24}, number = {2}, pages = {101-105}, doi = {10.1016/s0163-8343(01)00178-5}, pmid = {11869744}, issn = {0163-8343}, mesh = {Humans ; Pilot Projects ; *Primary Health Care ; Somatoform Disorders/*diagnosis ; }, abstract = {Somatization disorder (SD) patients are difficult to treat and produce negative feelings in health professionals. Smith et al.'s guidelines have demonstrated cost-effectiveness in the treatment of these patients, but family doctors consider it difficult to put these into practice in the long term. The objective of this paper is to design and assess a pilot course, based on Smith's norms, to train general practitioners for the everyday management of SD patients in primary care. We have designed a 20-h practical course, using role-playing and video recording with standardized patients, and focusing on micro-skills recommended by the literature on the subject. Assessment of the efficacy of the course is made by evaluation of baseline and post course video recordings by researchers unaware of the order of the interviews. The comparison of baseline and post course assessments demonstrated a significant improvement in several key skills (giving a name to the illness, explaining the psychological and biological basis of the disease, and emphasizing stress reduction) but no change on others (explaining that SD is a well-known disorder, empowering the patient, not blaming the patient for his or her illness, and instilling hope). Finally, other skills such as assessing the patient's opinion of the illness, recognizing the reality of symptoms and informing that there is no life risk, were correctly done from the beginning and, therefore, showed no change. We found that training may facilitate the development of certain skills. However, some doctors' abilities might also require the use of techniques such as Balint groups to modify negative emotions, such as anger and fear, toward these patients.}, } @article {pmid11853140, year = {2002}, author = {Choi, M and Seo, M and Jung, J and Lee, K and Yoon, J and Chang, D and Park, RD}, title = {Evaluation of canine gastric motility with ultrasonography.}, journal = {The Journal of veterinary medical science}, volume = {64}, number = {1}, pages = {17-21}, doi = {10.1292/jvms.64.17}, pmid = {11853140}, issn = {0916-7250}, mesh = {Animals ; Cross-Sectional Studies ; Dogs/metabolism/*physiology ; Gastric Emptying/*physiology ; Pyloric Antrum/*diagnostic imaging/physiology ; Ultrasonography ; }, abstract = {For the evaluation of canine gastric motility with ultrasonography, contraction number of pyloric antrum and gastric emptying time (GET) by area and volume method developed by Bolondi et al.'s method were studied in 14 dogs. All experimental dogs were administered with saline and soup solution (10 ml/kg, B.W.). The mean values of contraction number of pyloric antrum in saline and soup group were 4.19 +/- 1.30/min and 4.82 +/- 0.65/min before feeding, and overall mean values were 4.66 +/- 1.37/min and 5.13 +/- 1.71/min, respectively. The mean values of the GET by area and volume method were 36.73 +/- 11.27, 40.00 +/- 8.87 min in saline group and 61.35 +/- 17.58, 59.11 +/- 14.46 min in soup group. In the GET in saline and soup groups, there was no significant difference between the area and volume method (p>0.05). Therefore, Bolondi et al.'s method by ultrasound can be used to evaluate the antropyloric motility and gastric emptying time with area and volume methods. The area method is easier to determine the GET than the volume method, but the latter is more accurate.}, } @article {pmid11852186, year = {2002}, author = {Obrenovitch, TP and Godukhin, OV and Chazot, PL}, title = {Repetitive spreading depression induces nestin protein expression in the cortex of rats and mice. Is this upregulation initiated by N-methyl-D-aspartate receptors?.}, journal = {Neuroscience letters}, volume = {320}, number = {3}, pages = {161-163}, doi = {10.1016/s0304-3940(02)00046-0}, pmid = {11852186}, issn = {0304-3940}, mesh = {Animals ; Astrocytes/metabolism ; Brain Injuries/metabolism/physiopathology ; Cell Survival/drug effects/physiology ; Cerebral Cortex/cytology/drug effects/*metabolism ; Cortical Spreading Depression/drug effects/*physiology ; Excitatory Amino Acid Antagonists/pharmacology ; Gene Expression Regulation/drug effects/physiology ; Immunohistochemistry ; Intermediate Filament Proteins/drug effects/*metabolism ; Ischemic Preconditioning ; Male ; Mice ; Mice, Inbred C57BL ; *Nerve Tissue Proteins ; Nestin ; Neurons/cytology/drug effects/*metabolism ; Potassium Chloride/pharmacology ; Rats ; Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors/*metabolism ; Synaptic Transmission/drug effects/*physiology ; Up-Regulation/drug effects/*physiology ; }, abstract = {In the November issue (2001) of Neuroscience Letters, Holmin et al. (Neurosci. Lett. 314 (2001) 151) reported that the synthesis of the intermediate filament protein nestin was upregulated by potassium-induced depolarization in the rat cortex. In this letter, we provide supplementary evidence that repeated cortical spreading depression elicited by potassium induces a delayed upregulation of nestin. However, we argue against the authors' conclusion, "Nestin expression was N-methyl-D-aspartate (NMDA)-receptor dependent since dizocilpine (MK-801) treatment abolished the response" because spreading depression itself is very sensitive to NMDA-receptor block, and the drug treatment was initiated prior to potassium application to the cortex in Holmin et al.'s study.}, } @article {pmid11847873, year = {2001}, author = {Fawdry, MK}, title = {An explication of nursing and family caring for older adults.}, journal = {Journal of holistic nursing : official journal of the American Holistic Nurses' Association}, volume = {19}, number = {3}, pages = {285-296}, doi = {10.1177/089801010101900308}, pmid = {11847873}, issn = {0898-0101}, mesh = {Activities of Daily Living ; *Adaptation, Psychological ; Aged ; Aged, 80 and over ; Caregivers/*psychology ; *Cooperative Behavior ; Female ; *Holistic Nursing ; Humans ; Male ; *Professional-Family Relations ; Quality of Life ; }, abstract = {The purpose of this article is to present a holistic approach to the care of older adults by family members who are steadily assuming more responsibility for their care. Nurses can greatly enhance this care through the establishment of collaborative partnerships with family caregivers. Nursing and family caring as collaborative partnerships build on Harvath et al.'s work on establishing partnerships with family caregivers and Bowers' theory of intergenerational caregiving. Through the use of nursing and family caring as collaborative partnerships, nurses can empower family members to promote the health of older adults.}, } @article {pmid11827447, year = {2002}, author = {Yamada, J}, title = {Neurological origins of poor reading comprehension despite fast word decoding?.}, journal = {Brain and language}, volume = {80}, number = {2}, pages = {253-259}, doi = {10.1006/brln.2001.2565}, pmid = {11827447}, issn = {0093-934X}, mesh = {Child ; *Cognition ; Humans ; *Hydrocephalus ; *Reading ; *Vocabulary ; }, abstract = {Barnes, Faulkner, and Dennis (2001) found that hydrocephalic children (mean age = 11.5 years) of average or above-average verbal intelligence exhibit poor reading comprehension despite their fast and accurate decoding skills on individual words. This finding attracts the attention of reading researchers because it appears to be against the following standard principle of reading comprehension failure (Gough & Hillinger, 1980), thereby provoking basic issues centering around it (e.g., Stanovich, 1991): Reading Comprehension = Word Decoding x Listening Comprehension. This formula indicates that when listening comprehension is kept well within the normal range, reading comprehension is highly correlated with word decoding (e.g., Perfetti, 1985). In contrast, with poor listening comprehension children would be poor readers however good they may be at reading words (e.g., Cain, Oakhill, & Bryant, 2000). Although Barnes et al. clearly demonstrated that children with hydrocephalus decoded individual words better than they comprehended text, it is not readily apparent whether their findings are inconsistent with the standard principle. The purpose of the present article is twofold. The first is to examine whether Barnes et al.'s findings constitute a counterexample of the above principle. (Note that Barnes et al. did not address this question.) The second and more important purpose is to discuss the possible origins of the decoding-better-than-sentence/text-comprehension pattern. We also present some pedagogical implications for poor readers such as hydrocephalic children.}, } @article {pmid11827081, year = {2002}, author = {Strain, E and Patterson, K and Seidenberg, MS}, title = {Theories of word naming interact with spelling-sound consistency.}, journal = {Journal of experimental psychology. Learning, memory, and cognition}, volume = {28}, number = {1}, pages = {207-14; discussion 215-20}, doi = {10.1037/0278-7393.28.1.207}, pmid = {11827081}, issn = {0278-7393}, mesh = {Adult ; Female ; Humans ; *Imagination ; Male ; *Mental Recall ; Middle Aged ; *Phonetics ; Psycholinguistics ; *Semantics ; *Verbal Learning ; }, abstract = {In a previous study (E. Strain, K. Patterson, & M. S. Seidenberg, 1995), the authors concluded that word naming is characterized by an interaction between spelling-sound typicality and word imageability, thus implicating a role for word meaning in the naming process. J. Monaghan and A. W. Ellis (2002) reject E. Strain et al.'s conclusion, arguing that it is age of acquisition (AoA) and not imageability that interacts with spelling-sound typicality. In this article, the authors question their alternative interpretation (a) by raising a number of conceptual and methodological issues germane to this debate and (b) by presenting new data that confirm a significant interaction between spelling-sound typicality and imageability in word-naming latencies, an interaction that is reliable when word AoA is controlled in a regression analysis.}, } @article {pmid11824742, year = {2001}, author = {Abdel-Khalek, AM and Rudwan, S}, title = {The Kuwait University Anxiety Scale: reliability and criterion-related validity in Syrian college students.}, journal = {Psychological reports}, volume = {89}, number = {3}, pages = {718}, doi = {10.2466/pr0.2001.89.3.718}, pmid = {11824742}, issn = {0033-2941}, mesh = {Adult ; Anxiety/*diagnosis/psychology ; *Cross-Cultural Comparison ; Female ; Humans ; Male ; Personality Inventory/*statistics & numerical data ; Psychometrics ; Reproducibility of Results ; Students/psychology ; Syria ; }, abstract = {The Kuwait University Anxiety Scale was administered to 51 male and 56 female undergraduates in Syria. Respectively, the coefficients alpha for men, women, and the whole group were .91, .92, and .92; the test-retest rs after 14 to 21 days .88, .81, and .84; and the criterion-related validities .64, .62, and .64 against scores on Spielberger, et al.'s Trait Anxiety scale.}, } @article {pmid11800690, year = {2002}, author = {Ancey, C}, title = {Dry granular flows down an inclined channel: experimental investigations on the frictional-collisional regime.}, journal = {Physical review. E, Statistical, nonlinear, and soft matter physics}, volume = {65}, number = {1 Pt 1}, pages = {011304}, doi = {10.1103/PhysRevE.65.011304}, pmid = {11800690}, issn = {1539-3755}, abstract = {This paper presents experimental results on dry granular flows down an inclined rough channel. Different flow regimes were identified depending on the Froude number. For Froude numbers exceeding a critical value (function of the channel slope), flow was characterized by a fairly linear velocity profile and a discharge equation in the form q varies with h(n) with q the flow rate per unit width, h the flow depth, and n an exponent in the range 2-3 (regime A). When the Froude number was lower than the critical value, the flow was characterized by a convex velocity profile and a discharge equation of the form q varies with h(n), with n ranging from 0.97 to 1.16, producing the striking result that the mean velocity was constant for a given inclination of the channel (regime B). Experimental data were used to test three theoretical models developed to describe dry granular flows in a frictional-collisional regime. Savage's model provides results that capture experimental trends well and yield the correct magnitude for velocity and discharge for regime A, but it reproduces the dependence of the discharge on the channel slope for only a narrow range of slopes [S. B. Savage, in U.S./Japan Seminar on New Models and Constitutive Relations in the Mechanics of Granular Materials, Ithaca, 1982, edited by J. T. Jenkins and M. Satake (Elsevier Science Publishers, Amsterdam, 1982), p. 261]. In contrast, Mills et al.'s model is less refined and requires fitting an input parameter to give the correct magnitude of velocity but it successfully accounts for the variation in the discharge with slope for regime A for a wide range of slopes [Mills, Loggia, and Tixier, Europhys. Lett. 45, 733 (1999); Eur. Phys. J. E 1, 5 (2000)]. Ancey and Evesque's model is also crude in determining the density profile but manages to provide velocity profiles and discharge equations in good agreement with experimental data for regime B [C. Ancey and P. Evesque, Phys. Rev. E 62, 8349 (2000)].}, } @article {pmid11791530, year = {2001}, author = {Longabaugh, R}, title = {Comments on Dunn et al.'s "The use of brief interventions adapted from motivational interviews across behavioral domains: a systematic review". Why is motivational interviewing effective?.}, journal = {Addiction (Abingdon, England)}, volume = {96}, number = {12}, pages = {1773-4; discussion 1774-5}, pmid = {11791530}, issn = {0965-2140}, mesh = {Behavior Therapy/*methods ; Evidence-Based Medicine ; Humans ; *Motivation ; Treatment Outcome ; }, } @article {pmid11791529, year = {2001}, author = {Heather, N}, title = {Comments on Dunn et al.'s "The use of brief interventions adapted from motivational interviewing across behavioral domains: a systematic review". Motivational interviewing: effectiveness and cost-effectiveness.}, journal = {Addiction (Abingdon, England)}, volume = {96}, number = {12}, pages = {1772-3; discussion 1774-5}, pmid = {11791529}, issn = {0965-2140}, mesh = {Behavior Therapy/*economics/methods ; Cost-Benefit Analysis ; Humans ; *Motivation ; Treatment Outcome ; }, } @article {pmid11791528, year = {2001}, author = {Miller, WR}, title = {Comments on Dunn et al.'s "The use of brief interventions adapted from motivational interviewing across behavioral domains: a systematic review". When is it motivational interviewing?.}, journal = {Addiction (Abingdon, England)}, volume = {96}, number = {12}, pages = {1770-2; discussion 1774-5}, pmid = {11791528}, issn = {0965-2140}, mesh = {Behavior Therapy/methods/*standards ; Clinical Competence ; Humans ; *Motivation ; *Quality Assurance, Health Care ; }, } @article {pmid11791509, year = {2001}, author = {Al-Adwani, A}, title = {Needle fixation is as elusive as ever: comments on McBride et al.'s "Needle fixation, the drug user's perspective: a qualitative study".}, journal = {Addiction (Abingdon, England)}, volume = {96}, number = {11}, pages = {1676-1677}, pmid = {11791509}, issn = {0965-2140}, mesh = {Humans ; *Needles ; *Object Attachment ; }, } @article {pmid11789432, year = {2001}, author = {Koenig, CS and Griggs, RA}, title = {Elementary, my dear Wason: the role of problem representation in the THOG task.}, journal = {Psychological research}, volume = {65}, number = {4}, pages = {289-293}, doi = {10.1007/s004260100067}, pmid = {11789432}, issn = {0340-0727}, mesh = {Adult ; *Attention ; Humans ; Logic ; *Mental Recall ; Pattern Recognition, Visual ; *Problem Solving ; Writing ; }, abstract = {The present study was concerned with Wason's THOG problem, a hypothetico-deductive reasoning task for which performance over the past 20 years has typically been very poor (< 20% correct). We examined the hypothesis that incorporating a quasi-visual context into the problem statement would make both the binary, symmetric tree structure and solution principle of the THOG task clearer and thus facilitate performance. A version of O'Brien et al.'s (Q J Exp Psychol 42A:329-351) Blackboard THOG problem, that specifies each branch of the tree by describing a specific location for each possible color-shape combination, was used to test this hypothesis. Substantial facilitation was both observed (68% correct) and replicated (73% correct), and it was also shown that it is necessary to provide a representation of both sides of the tree to obtain this level of facilitation. The implications of these results for human deductive reasoning are considered.}, } @article {pmid11784469, year = {2001}, author = {Rollnick, S}, title = {Comments on Dunn et al.'s "The use of brief interventions adapted from motivational interviewing across behavioral domains: a systematic review". Enthusiasm, quick fixes and premature controlled trials.}, journal = {Addiction (Abingdon, England)}, volume = {96}, number = {12}, pages = {1769-70; discussion 1774-5}, doi = {10.1080/09652140120089517}, pmid = {11784469}, issn = {0965-2140}, mesh = {Behavior Therapy/*methods ; Humans ; *Motivation ; Psychotherapy, Brief/*methods ; Treatment Outcome ; }, } @article {pmid11775719, year = {2001}, author = {Dear, GE and Slattery, JL and Hillan, RJ}, title = {Evaluations of the quality of coping reported by prisoners who have self-harmed and those who have not.}, journal = {Suicide & life-threatening behavior}, volume = {31}, number = {4}, pages = {442-450}, doi = {10.1521/suli.31.4.442.22039}, pmid = {11775719}, issn = {0363-0234}, mesh = {*Adaptation, Psychological ; Adult ; Female ; Humans ; Male ; Middle Aged ; Personality Inventory ; Prisoners/*psychology ; Problem Solving ; Self-Injurious Behavior/*psychology ; }, abstract = {Yufit and Bongar (1992) argued that a deficiency in coping skills is an important risk factor for suicidal behavior. Dear, Thomson, Hall, and Howells (1998) found that prisoners who had self-harmed in the past 3 days were less likely than a comparison group to have used problem-solving or active cognitive coping strategies to handle the most significant stressor of the past week, but it was not clear whether this represented a difference in the quality of coping responses used. In this study, three groups of blind raters (prisoners, prison officers, and forensic psychologists) rated the coping responses of the participants in Dear et al.'s study. The coping responses of self-harmers were judged less beneficial and more risky. Problem-solving strategies were most often cited as contributing to beneficial outcomes and the catharsis strategies employed by self-harmers were most often judged to be counterproductive. It remains unclear whether prisoners who self-harmed routinely employ poor quality coping strategies or if they simply used poor quality coping on this occasion.}, } @article {pmid11747584, year = {2001}, author = {Rouder, JN and Gomez, P}, title = {Modelling serial position curves with temporal distinctiveness.}, journal = {Memory (Hove, England)}, volume = {9}, number = {4}, pages = {301-311}, doi = {10.1080/09658210042000102}, pmid = {11747584}, issn = {1464-0686}, abstract = {We offer a critique of the temporal distinctiveness model of serial position effects (Nairne, Neath, Serra, & Byun, 1997). The temporal distinctiveness model combines a precise definition of stimulus distinctiveness with a memory perturbation process. The critique is empirically motivated-we show that with a more complete analysis, the temporal distinctiveness model does not adequately account for Nairne et al.'s experimental data. To better account for the data, we independently modified two components of Nairne et al.'s model: the mathematical form of the definition of temporal distinctiveness and the mathematical form of the mapping from distinctiveness to free-recall probabilities. Both of these modifications provided for better fits. Yet both Nairne et al.'s definition and our modified definition are fairly arbitrary. We show that a significant challenge to this approach is to find theoretically motivated constraints of the temporal distinctiveness model while providing for adequate fits to data.}, } @article {pmid11736159, year = {2001}, author = {Rim, S and Kim, MW and Hwang, DU and Park, YJ and Kim, CM}, title = {Reconsideration of intermittent synchronization in coupled chaotic pendula.}, journal = {Physical review. E, Statistical, nonlinear, and soft matter physics}, volume = {64}, number = {6 Pt 1}, pages = {060101}, doi = {10.1103/PhysRevE.64.060101}, pmid = {11736159}, issn = {1539-3755}, abstract = {We reinvestigate the intermittent synchronization phenomenon of coupled chaotic pendula that has recently been a controversy. We propose a simple numerical scheme by which one can easily determine whether the observed synchronization is a numerical artifact of computer analysis or not. By using this scheme, for certain coupling strength regime, we find that the average time taken for synchronization linearly depends on the precision of calculations. According to Longa et al.'s criterion for synchronization, this implies that the observed synchronization is genuine.}, } @article {pmid11734907, year = {2002}, author = {Nickle, DC and Learn, GH and Rain, MW and Mullins, JI and Mittler, JE}, title = {Curiously modern DNA for a "250 million-year-old" bacterium.}, journal = {Journal of molecular evolution}, volume = {54}, number = {1}, pages = {134-137}, doi = {10.1007/s00239-001-0025-x}, pmid = {11734907}, issn = {0022-2844}, support = {AI27757/AI/NIAID NIH HHS/United States ; }, mesh = {Bacteria/*genetics ; Crystallization ; *DNA, Bacterial ; *Evolution, Molecular ; Fossils ; Phylogeny ; Sequence Analysis, DNA ; }, abstract = {Studies of ancient DNA have attracted considerable attention in scientific journals and the popular press. Several of the more extreme claims for ancient DNA have been questioned on biochemical grounds (i.e., DNA surviving longer than expected) and evolutionary grounds (i.e., nucleotide substitution patterns not matching theoretical expectations for ancient DNA). A recent letter to Nature from Vreeland et al. (2000), however, tops all others with respect to age and condition of the specimen. These researchers extracted and cultured a bacterium from an inclusion body from what they claim is a 250 million-year (Myr)-old salt crystal. If substantiated, this observation could fundamentally alter views about bacterial physiology, ecology and evolution. Here we report on molecular evolutionary analyses of the 16S rDNA from this specimen. We find that 2-9-3 differs from a modern halophile, Salibacillus marismortui, by just 3 unambiguous bp in 16S rDNA, versus the approximately 59 bp that would be expected if these bacteria evolved at the same rate as other bacteria. We show, using a Poisson distribution, that unless it can be shown that S. marismortui evolves 5 to 10 times more slowly than other bacteria for which 16S rDNA substitution rates have been established, Vreeland et al.'s claim would be rejected at the 0.05 level. Also, a molecular clock test and a relative rates test fail to substantiate Vreeland et al.'s claim that strain 2-9-3 is a 250-Myr-old bacterium. The report of Vreeland et al. thus falls into a long series of suspect ancient DNA studies.}, } @article {pmid11726069, year = {2001}, author = {Rind, B and Tromovitch, P and Bauserman, R}, title = {The validity and appropriateness of methods, analyses, and conclusions in Rind et al. (1998): A rebuttal of victimological critique from Ondersma et al. (2001) and Dallam et al. (2001).}, journal = {Psychological bulletin}, volume = {127}, number = {6}, pages = {734-758}, doi = {10.1037/0033-2909.127.6.734}, pmid = {11726069}, issn = {0033-2909}, mesh = {*Adaptation, Psychological ; Adult ; Child ; Child Abuse, Sexual/*psychology ; Data Interpretation, Statistical ; Humans ; Meta-Analysis as Topic ; Reproducibility of Results ; Research Design/*standards ; *Social Adjustment ; *Social Values ; Terminology as Topic ; }, abstract = {The authors respond to 2 victimological critiques of their 1998 meta-analysis on child sexual abuse (CSA). S. J. Dallam et al. (2001) claimed that B. Rind, P. Tromovitch, and R. Bauserman (1998) committed numerous methodological and statistical errors, and often miscoded and misinterpreted data. The authors show all these claims to be invalid. To the contrary, they demonstrate frequent bias in Dallam et al.'s criticisms. S. J. Ondersma et al. (2001) claimed that Rind et al.'s study is part of a backlash against psychotherapists, that its suggestions regarding CSA definitions were extrascientific, and that the moral standard is needed to understand CSA scientifically. The authors show their suggestions to have been scientific and argue that it is Ondersma et al.'s issue-framing and moral standard that are extrascientific. This reply supports the original methods, analyses, recommendations, and conclusions of Rind et al.}, } @article {pmid11726068, year = {2001}, author = {Dallam, SJ and Gleaves, DH and Cepeda-Benito, A and Silberg, JL and Kraemer, HC and Spiegel, D}, title = {The effects of child sexual abuse: Comment on Rind, Tromovitch, and Bauserman (1998).}, journal = {Psychological bulletin}, volume = {127}, number = {6}, pages = {715-733}, doi = {10.1037/0033-2909.127.6.715}, pmid = {11726068}, issn = {0033-2909}, mesh = {*Adaptation, Psychological ; Child ; Child Abuse, Sexual/*psychology ; Data Interpretation, Statistical ; Humans ; Meta-Analysis as Topic ; Research Design/standards ; Sex Factors ; *Social Adjustment ; *Terminology as Topic ; }, abstract = {B. Rind, P. Tromovitch, and R. Bauserman (1998) examined the long-term effects of childhood sexual abuse (CSA) by meta-analyzing studies of college students. The authors reported that effects "were neither pervasive nor typically intense" and that "men reacted much less negatively than women" (p. 22) and recommended value-neutral reconceptualization of the CSA construct. The current analysis revealed numerous problems in that study that minimized CSA-adjustment relations, including use of a healthy sample, an inclusive definition of CSA, failure to correct for statistical attenuation, and misreporting of original data. Rind et al.'s study's main conclusions were not supported by the original data. As such, attempts to use their study to argue that an individual has not been harmed by sexual abuse constitute a serious misapplication of its findings.}, } @article {pmid11726067, year = {2001}, author = {Ondersma, SJ and Chaffin, M and Berliner, L and Cordon, I and Goodman, GS and Barnett, D}, title = {Sex with children is abuse: Comment on Rind, Tromovitch, and Bauserman (1998).}, journal = {Psychological bulletin}, volume = {127}, number = {6}, pages = {707-714}, doi = {10.1037/0033-2909.127.6.707}, pmid = {11726067}, issn = {0033-2909}, mesh = {Child ; Child Abuse, Sexual/*psychology ; Humans ; Meta-Analysis as Topic ; *Morals ; Peer Review/standards ; Research Design/standards ; *Social Values ; Terminology as Topic ; }, abstract = {B. Rind, P. Tromovitch, and R. Bauserman (1998) reported a meta-analysis of the relation between sexual abuse in childhood and adolescence and psychological functioning among college students. Several aspects of their work have proven to be highly controversial, including their assertion that the relation between child sexual abuse and adjustment is quite small and their questioning of whether child sexual abuse should be labeled abuse in scientific inquiry. In this commentary, the authors summarize the controversy that has ensued, place it in a historical context, discuss the limitations of B. Rind et al.'s findings, and critique the manner in which those findings are presented. The authors also argue for the appropriateness of the term abuse and for scientific terminology that reflects rather than contradicts consensual public morality.}, } @article {pmid11705017, year = {2001}, author = {Frost, RO and Meagher, BM and Riskind, JH}, title = {Obsessive-compulsive features in pathological lottery and scratch-ticket gamblers.}, journal = {Journal of gambling studies}, volume = {17}, number = {1}, pages = {5-19}, pmid = {11705017}, issn = {1050-5350}, mesh = {Adult ; Aged ; Disruptive, Impulse Control, and Conduct Disorders/diagnosis/psychology ; Female ; Gambling/*psychology ; Humans ; Male ; Middle Aged ; Obsessive-Compulsive Disorder/*diagnosis/psychology ; Personality Inventory ; }, abstract = {The results of this study support the notion that pathological gamblers drawn from the community would score higher on all three scores from the YBOCS than light gamblers. Consistent with hypotheses, pathological gamblers (lottery and scratch ticket) reported more obsessions, compulsions, and avoidance behavior than the light gamblers, and also reported having more urges to engage in injurious behaviors to themselves and others. These findings provide evidence that pathological gambling falls in a spectrum or family of disorders which have obsessive-compulsive disorder at its core. These findings support McElroy, Hudson, Philips, et al.'s (1993) suggestions of similarities between OCD and Impulse Control Disorders, and extend Blaszczynski (1999) findings of overlap between pathological gamblers and OCD in a treatment population. Heavy gamblers also reported significantly more hoarding symptoms and compulsive buying than light gamblers. More research in this area may show further evidence of a spectrum of disorders with obsessive compulsive disorder at its core, and show further links between impulse control disorders (such as pathological gambling) and OCD.}, } @article {pmid11702918, year = {2001}, author = {Paccagnella, M and Grove, JR}, title = {Attitudes towards high achievers in sport: an adaptation of Feather's Tall Poppy Scale.}, journal = {Journal of science and medicine in sport}, volume = {4}, number = {3}, pages = {310-323}, doi = {10.1016/s1440-2440(01)80040-2}, pmid = {11702918}, issn = {1440-2440}, mesh = {*Achievement ; Adolescent ; Adult ; *Attitude ; Female ; Humans ; Male ; Personality ; Psychological Tests/*standards ; Reproducibility of Results ; Self Concept ; Social Values ; Sports/*psychology ; Statistics as Topic ; }, abstract = {A sport-specific version of Feather et al.'s (1991) Tall Poppy Scale, the Sportsperson Attitude Scale, was correlated with measures of global self-esteem, deservingness, and aspects of perfectionism. Total Negative Attitude and Favour Fall were negatively correlated with estimates of how much high-profile sports performers deserved their present high position. while Favour Reward and global self-esteem were positively correlated with estimates of deservingness. All measures demonstrated adequate reliability. All three SPAS subscales were found to be significantly correlated with High Personal Standards (HPS), a measure of perfectionism with theoretical but undocumented relationships to tall poppy attitudes. Regression analyses revealed that HPS and deservingness were significant predictors of tall poppy attitudes. It was concluded that the Sportsperson Attitude Scale would benefit from further refinement, but that the current version possesses adequate integrity for use in studies of attitudes toward high achievers in sport.}, } @article {pmid11699674, year = {2001}, author = {Spencer, JP and Smith, LB and Thelen, E}, title = {Tests of a dynamic systems account of the A-not-B error: the influence of prior experience on the spatial memory abilities of two-year-olds.}, journal = {Child development}, volume = {72}, number = {5}, pages = {1327-1346}, doi = {10.1111/1467-8624.00351}, pmid = {11699674}, issn = {0009-3920}, mesh = {*Child Development ; Child, Preschool ; *Concept Formation ; Female ; Humans ; Male ; *Memory, Short-Term ; Models, Psychological ; *Problem Solving ; *Space Perception ; Systems Analysis ; }, abstract = {Recently, Smith, Thelen, and colleagues proposed a dynamic systems account of the Piagetian "A-not-B" error in which infants' errors result from general processes that make goal-directed actions to remembered locations. Based on this account, the A-not-B error should be a general phenomenon, observable in different tasks and at different points in development. Smith, Thelen, et al.'s proposal was tested using an A-not-B version of a sandbox task. During three training trials and three "A" trials, 2-year-olds watched as a toy was buried in a sandbox at Location A. Following a 10-s delay, children searched for the object. Across five experiments, children's (total N = 92) performance on the A trials was accurate. After the A trials, children watched as a toy was hidden at Location B, 8 to 10 inches from Location A. In all experiments, children's searches after a 10-s delay were significantly biased in the direction of Location A. Furthermore, this bias toward Location A decreased with repeated trials to Location B, as well as when children completed fewer trials to Location A. Together, these data suggest that A-not-B-type errors are pervasive across tasks and development.}, } @article {pmid11594353, year = {2001}, author = {Rouder, JN and Gomez, P}, title = {Modelling serial position curves with temporal distinctiveness.}, journal = {Memory (Hove, England)}, volume = {9}, number = {4-6}, pages = {301-311}, doi = {10.1080/09658210042000102}, pmid = {11594353}, issn = {0965-8211}, support = {HD MH44640/HD/NICHD NIH HHS/United States ; R01-DC01240/DC/NIDCD NIH HHS/United States ; }, mesh = {Humans ; Memory, Short-Term/*physiology ; *Models, Psychological ; Probability ; Psychological Tests ; Time Factors ; }, abstract = {We offer a critique of the temporal distinctiveness model of serial position effects (Nairne, Neath, Serra, & Byun, 1997). The temporal distinctiveness model combines a precise definition of stimulus distinctiveness with a memory perturbation process. The critique is empirically motivated-we show that with a more complete analysis, the temporal distinctiveness model does not adequately account for Nairne et al.'s experimental data. To better account for the data, we independently modified two components of Nairne et al.'s model: the mathematical form of the definition of temporal distinctiveness and the mathematical form of the mapping from distinctiveness to free-recall probabilities. Both of these modifications provided for better fits. Yet both Nairne et al.'s definition and our modified definition are fairly arbitrary. We show that a significant challenge to this approach is to find theoretically motivated constraints of the temporal distinctiveness model while providing for adequate fits to data.}, } @article {pmid11584790, year = {2001}, author = {Meehan, JC and Holtzworth-Munroe, A and Herron, K}, title = {Maritally violent men's heart rate reactivity to marital interactions: a failure to replicate the Gottman et al. (1995) typology.}, journal = {Journal of family psychology : JFP : journal of the Division of Family Psychology of the American Psychological Association (Division 43)}, volume = {15}, number = {3}, pages = {394-408}, doi = {10.1037//0893-3200.15.3.394}, pmid = {11584790}, issn = {0893-3200}, support = {R01-MH51935/MH/NIMH NIH HHS/United States ; }, mesh = {Adaptation, Psychological/*physiology ; Adult ; *Conflict, Psychological ; Female ; *Heart Rate ; Humans ; Male ; *Personality Disorders ; Psychiatric Status Rating Scales ; Risk Factors ; Spouse Abuse/classification/*psychology ; Stress, Psychological ; Violence/psychology ; }, abstract = {In an attempt to replicate the J. M. Gottman et al. (1995) batterer typology, 58 men who had engaged in moderate-to-severe marital violence in the past year were studied. The sample was split into Gottman et al.'s Type 1 men (i.e., whose heart rates decreased, from baseline, during a marital conflict task) and Type 2 men (i.e., whose heart rates increased). The groups did not differ in the manner predicted on measures of marital violence, antisocial or aggressive-sadistic personality, drug dependence, criminality, general violence, childhood exposure to interparental violence, behavior during marital interactions, or relationship stability. Contrary to expectations, wives of Type 1 men rated their husband as more jealous and angry and reported more marital distress. In the only finding consistent with Gottman et al., Type 2 men scored higher on a measure of dependent personality. Implications for future research are discussed.}, } @article {pmid11580122, year = {2001}, author = {Yoon, TR and Rowe, SM and Chung, JY and Song, EK and Jung, ST and Anwar, IB}, title = {Clinical and radiographic outcome of femoral head fractures: 30 patients followed for 3-10 years.}, journal = {Acta orthopaedica Scandinavica}, volume = {72}, number = {4}, pages = {348-353}, doi = {10.1080/000164701753541998}, pmid = {11580122}, issn = {0001-6470}, mesh = {Accidental Falls ; Accidents, Traffic ; Adolescent ; Adult ; Aged ; Arthroplasty, Replacement, Hip ; Bone Screws ; Female ; Femur Head/*injuries ; Follow-Up Studies ; Fracture Fixation, Internal/instrumentation/*methods ; Fracture Healing ; Hip Fractures/classification/*diagnostic imaging/etiology/*surgery ; Humans ; Male ; Middle Aged ; Osteotomy ; Patient Selection ; Radiography ; Time Factors ; Treatment Outcome ; }, abstract = {The aim of this study was to evaluate the outcome of 30 femoral head fractures. We modified Pipkin's classification into 4 types: I (5 cases) small fracture of head distal to fovea centralis, which was too small or too fragmented to be fixed with screws; II (18 cases), larger fracture of head distal to fovea centralis; III (4 cases), large fracture of head proximal to fovea centralis, and IV (3 cases), comminuted fracture of head. Excision of the head fragment was done in all 5 cases of type I and in 9 type II fractures. Fixation of the head fragment was performed in 9 type II and in all 4 type III cases. The femoral head was replaced in all 3 type IV fractures. After a mean follow-up of 3-10 years, the clinical outcome, according to Epstein et al.'s critieria, were excellent in 7, good in 15, fair in 4 and poor in 1, except in type IV, and the radiographic outcome was excellent in 15, good in 7, fair in 4 and poor in 1. On the basis of our findings, we conclude that excision of the small fragment is a good choice of treatment in type 1. Early accurate reduction with stable internal fixation in type II or III permits bony union. Arthroplasty seems to be indicated in type IV.}, } @article {pmid11569589, year = {2001}, author = {Goldstein, G and Johnson, CR and Minshew, NJ}, title = {Attentional processes in autism.}, journal = {Journal of autism and developmental disorders}, volume = {31}, number = {4}, pages = {433-440}, pmid = {11569589}, issn = {0162-3257}, support = {NS33355/NS/NINDS NIH HHS/United States ; }, mesh = {Adolescent ; *Attention ; Autistic Disorder/*psychology ; Cognition Disorders/diagnosis ; Humans ; Problem Solving ; Psychomotor Disorders/diagnosis/etiology ; }, abstract = {Attentional processes in individuals with high-functioning autism were compared with a matched control group. Participants for the study were 103 children and adults with autism and 103 control subjects. Measures administered corresponded to Mirsky et al.'s (1991) factor analysis of tests of attention. Diminished performance was noted on measures that loaded on the Focus-Execute and Shift factors, but not on the Sustain and Encode factors. For tests in which psychomotor speed was used as the score, and the difference between groups was significant, covariance analyses were performed, using tests of basic motor functions as covariates. This procedure led to attenuation to the point of nonsignificant differences in the case of some of the attention tests. Thus, this comprehensive analysis of attention in individuals with high-functioning autism only found differences on measures in which the task placed demands on cognitive flexibility or psychomotor speed. Thus, purported attention deficits in autism may actually be primary deficits in complex decision making or psychomotor abilities.}, } @article {pmid11566424, year = {2001}, author = {Muller, M and Lupi-Pegurier, L and Quatrehomme, G and Bolla, M}, title = {Odontometrical method useful in determining gender and dental alignment.}, journal = {Forensic science international}, volume = {121}, number = {3}, pages = {194-197}, doi = {10.1016/s0379-0738(01)00399-1}, pmid = {11566424}, issn = {0379-0738}, mesh = {Adult ; Chi-Square Distribution ; *Cuspid ; Female ; *Forensic Dentistry ; Humans ; Male ; Odontometry/*methods ; *Population Surveillance ; *Sex ; }, abstract = {Rao et al.'s method of sex determination, which considers the mandibular canine index (MCI) is one giving satisfactory results. However, they did not take occlusion into consideration. The aim of this study, therefore, was to evaluate the effectiveness of this method with respect to tooth alignment. The study population involved the students enrolled in the University of Nice-Sophia Antipolis. Two hundred and ten girls and 214 boys were randomly sampled (1/20). Both tooth sizes and dental arches were measured using a vernier calliper to calculate MCI for both sexes. The results were compared to standard MCI, taking into account tooth alignment.Rao et al.'s method can only be used in the case of correct lower-anterior dental alignment and by using the standard MCI of the local population.}, } @article {pmid11562447, year = {2001}, author = {Guermonprez, L and Ducrocq, C and Gaudry-Talarmain, YM}, title = {Inhibition of acetylcholine synthesis and tyrosine nitration induced by peroxynitrite are differentially prevented by antioxidants.}, journal = {Molecular pharmacology}, volume = {60}, number = {4}, pages = {838-846}, pmid = {11562447}, issn = {0026-895X}, mesh = {Acetates/metabolism ; Acetylcholine/*antagonists & inhibitors/biosynthesis ; Animals ; Antioxidants/*pharmacology ; Biological Transport/drug effects ; Carbon Radioisotopes ; Choline/metabolism ; Choline O-Acetyltransferase/antagonists & inhibitors/*metabolism ; Drug Interactions ; Molsidomine/analogs & derivatives/pharmacology ; Nitrates/*pharmacology ; Oxidants/*pharmacology ; Reducing Agents/pharmacology ; Torpedo ; Tyrosine/*analogs & derivatives/*metabolism ; Uric Acid/pharmacology ; }, abstract = {Evidence of an overload of reactive oxygen species and peroxynitrite, a derivative of nitric oxide, in sporadic amyotrophic lateral sclerosis suggests that peroxynitrite could impair cholinergic functions. Because of the impossibility of obtaining synaptosomes from vertebrate neuromuscular junctions, we used cholinergic synaptosomes purified from Torpedo marmorata electroneurons to characterize the defects triggered by peroxynitrite in more detail. Addition of peroxynitrite or its donor 3-morpholinosydnonimine abolished high-affinity choline uptake and synthesis of acetylcholine from acetate. T. marmorata choline acetyltransferase (ChAT) was impaired to the same extent as bovine brain ChAT. A hallmark of peroxynitrite action is the nitration of tyrosine residues in proteins. Peroxynitrite induced a concentration-dependent appearance of nitrotyrosines in several neuronal proteins from synaptosomes and, more readily, from synaptic vesicles. Peroxynitrite also triggered tyrosine nitrations in purified ChAT. Peroxynitrite-dependent nitrations were impaired when synaptosomes were pretreated with thioreductants (glutathione, N-acetyl cysteine, dithiothreitol) or antioxidants (uric acid, melatonin, bovine serum albumin, desferrioxamine). Deleterious effects of peroxynitrite on choline transport and ChAT activity were prevented by the thioreductants but only partially by the antioxidants, suggesting a mechanism other than tyrosine nitration, which may involve cysteine oxidation. Further development of protective agents acting on choline transport and on ChAT activity may offer interesting therapeutic possibilities with respect to cholinergic dysfunction occurring in neurodegenerative diseases.}, } @article {pmid11552754, year = {2001}, author = {Gergely, G}, title = {Is early differentiation of human behavior a precursor to the 1-year-old's understanding of intentional action? Comment on Legerstee, Barna, and DiAdamo (2000).}, journal = {Developmental psychology}, volume = {37}, number = {5}, pages = {579-82; discussion 583-6}, doi = {10.1037//0012-1649.37.5.579}, pmid = {11552754}, issn = {0012-1649}, mesh = {*Behavior ; *Child Development ; *Cognition ; Humans ; Infant ; Psychological Theory ; *Psychology, Child ; }, abstract = {In a recent issue of Developmental Psychology, M. Legerstee, J. Barna, and C. DiAdamo (2000) reported a study showing that 6-month-olds expect people to talk to persons rather than to inanimate objects and to manipulate inanimates rather than persons. They interpreted this ability as a "precursor" to later understanding of intentionality. The present article takes issue with the authors' 2 different levels of interpretation that contradict each other and raise problems in their own right. It is suggested that M. Legerstee et al.'s finding is most parsimoniously explained by associative learning and may not constitute a precursor to later understanding of intentionality in any well-defined sense of the term. The present article argues for the importance of differentiating between associative and inferential processes and reviews evidence that the understanding of goal-directed action around 9 months of age involves principle-based inferences.}, } @article {pmid11550738, year = {2001}, author = {Perez, M and Pettit, JW and David, CF and Kistner, JA and Joiner, TE}, title = {The interpersonal consequences of inflated self-esteem in an inpatient psychiatric youth sample.}, journal = {Journal of consulting and clinical psychology}, volume = {69}, number = {4}, pages = {712-716}, pmid = {11550738}, issn = {0022-006X}, mesh = {Adolescent ; Child ; Child Behavior Disorders/*psychology/therapy ; Female ; Hospitals, Psychiatric ; Humans ; *Interpersonal Relations ; Male ; Mood Disorders/*psychology/therapy ; *Patient Admission ; *Peer Group ; Personality Assessment ; Rejection, Psychology ; *Self Concept ; Social Environment ; Sociometric Techniques ; }, abstract = {This study tested R. F. Baumeister, L. Smart, and J. M. Boden's (1996) theory of inflated self-esteem with an inpatient psychiatric youth sample. Participants were assessed on their self-reported self-esteem, self-reported interpersonal problems, and peer rejection (measured by evaluations from 3 or 4 peers). Consistent with the hypotheses, those with low self-esteem reported the most interpersonal problems, followed consecutively by the moderate self-esteem group and then the high self-esteem group, who reported the fewest interpersonal problems. Also in line with the hypotheses, those with low and high self-esteem were rejected by their peers when compared with the moderate self-esteem group. Thus, the high self-esteem group was rejected by their peers but did not themselves report interpersonal problems. These findings provide further support for Baumeister et al.'s theory and generalize the theory to a clinical setting.}, } @article {pmid11536314, year = {2001}, author = {Leinfelder, I and de Vries, H and Deleu, R and Nelissen, M}, title = {Rank and grooming reciprocity among females in a mixed-sex group of captive hamadryas baboons.}, journal = {American journal of primatology}, volume = {55}, number = {1}, pages = {25-42}, doi = {10.1002/ajp.1036}, pmid = {11536314}, issn = {0275-2565}, mesh = {Aggression ; Animals ; Feeding Behavior ; Female ; *Grooming ; Male ; Papio/*psychology ; *Social Dominance ; Stress, Psychological ; }, abstract = {In a mixed-sex, captive group of hamadryas baboons (Papio hamadryas hamadryas) we investigated whether female grooming relationships are affected by their dominance ranks. Seyfarth's [1977] grooming for support model and Barrett et al.'s [1999] biological market model both predict that in primate groups where competition for monopolizable resources is high, grooming among females is based, at least partly, on the interchange of grooming for rank-related benefits, and that rank thus influences the distribution of grooming in females. Contrary to this prediction, our results show that despite the existence of a linear dominance hierarchy, rather strict dominance relationships, and high food-related aggression rates, grooming among female hamadryas baboons is not affected by rank and is only exchanged for itself. This is understandable since rank differences in our study group only result in differential access to limited, preferred food items that are not actively shared. Although some females are more likely to tolerate one another at the food pile, this tolerance is not determined by their grooming efforts and interchange of grooming for rank-related benefits does not occur. We conclude that female hamadryas baboons groom others in order to be groomed by them, which is supported by our observation that grooming reciprocity within a dyad increases when more grooming occurs in this dyad. Our results indicate that grooming is indeed a valuable commodity in itself, probably because of its stress- and tension-reducing effect. Based on our findings, the existing groom trade model is extended to include circumstances in which monopolizable resources are available but are not traded for grooming.}, } @article {pmid11529521, year = {2001}, author = {Straub, K and Wilson, C and McCollum, C and Badecker, W}, title = {Prosodic structure and wh-questions.}, journal = {Journal of psycholinguistic research}, volume = {30}, number = {4}, pages = {379-394}, pmid = {11529521}, issn = {0090-6905}, mesh = {Adult ; Female ; Humans ; Language ; *Linguistics ; Male ; Speech ; Speech Production Measurement ; }, abstract = {This study examines the influence of wh-gaps on the prosodic contour of spoken utterances. A previous study (Nagel, Shapiro, & Nawy, 1994) claimed that the phonological representation of a sentence containing a filler-gap dependency explicitly encodes the location of the syntactic gap. In support of this hypothesis, Nagel et al. presented evidence that the word immediately preceding a gap is lengthened and that there is a reliable increase in pitch excursion across the gap location. Our study challenges Nagel et al.'s claim. We argue that their materials confounded the presence/ absence of a gap with other factors that are known to affect intonational phrasing independently. We show that, when these factors are separated, the evidence that syntactic gaps are explicitly encoded in the phonological representation of a sentence disappears.}, } @article {pmid11519629, year = {2001}, author = {Petry, NM}, title = {Challenges in the transfer of contingency management techniques: comment on Silverman et al. (2001).}, journal = {Experimental and clinical psychopharmacology}, volume = {9}, number = {1}, pages = {24-6; discussion 35-9}, doi = {10.1037/1064-1297.9.1.24}, pmid = {11519629}, issn = {1064-1297}, support = {P50-AA03510/AA/NIAAA NIH HHS/United States ; R01-DA13444/DA/NIDA NIH HHS/United States ; R29-DA12056/DA/NIDA NIH HHS/United States ; }, mesh = {Adult ; Female ; Humans ; Pregnancy ; Rehabilitation, Vocational/*psychology ; Reinforcement, Psychology ; Substance-Related Disorders/*rehabilitation ; Workplace/*psychology ; }, abstract = {This article critiques K. Silverman, D. Svikis, E. Robles, M. L. Stitzer, and G. E. Bigelow's (2001) study of a contingency management intervention for reinforcing development of job-related skills in substance abusing women. The strengths of Silverman et al.'s study include studying a patient population of major public health concern, expanding contingency management techniques to a vocational training setting, reinforcing gradual approximations, implementing the intervention for a long duration, and carefully designing and executing the experimental procedures. However, many of these strengths may also be interpreted as weaknesses if the ultimate goal is to apply contingency management techniques in self-sustaining, community-based settings. The need to evaluate long-term cost-effectiveness of these procedures is described, and the difficulties in transferring contingency management techniques to real-world settings is discussed.}, } @article {pmid11512853, year = {2001}, author = {Wei, S and Li, Z and Yin, S and Zhang, X and Liu, W and Wang, X}, title = {Annealed crystallization of ultrafine amorphous NiB alloy studied by XAFS.}, journal = {Journal of synchrotron radiation}, volume = {8}, number = {Pt 2}, pages = {566-568}, doi = {10.1107/s0909049500018070}, pmid = {11512853}, issn = {0909-0495}, abstract = {XAFS has been used to investigate the local structure evolutions of ultrafine amorphous NiB alloy during the annealed crystallization process. A nanocrystalline Ni phase with the local structure of crystalline Ni-like and a crystalline Ni3B, have been produced for ultrafine amorphous NiB alloy under the annealed temperature of 573 K. The results rule out Rojo et al.'s devitrification mechanism of Ni80B20 amorphous alloy in which they considered that an amorphous pure Ni phase is formed in the first exothermic process. However, our results are almost identical with Riveiro et al.'s conclusion in which the intermediate state is interpreted as two metastable crystalline phases of Ni3B and Ni-rich NiB alloy. With the annealed temperature going onto 773 K, the ultrafine NiB sample is further decomposed and crystallized into crystalline Ni with long-range order.}, } @article {pmid11482825, year = {2001}, author = {Melis, M}, title = {Dr. Melis comments on Raigrodski, et al.'s article in the January 2001 issue of CRANIO.}, journal = {Cranio : the journal of craniomandibular practice}, volume = {19}, number = {3}, pages = {149}, pmid = {11482825}, issn = {0886-9634}, mesh = {Amitriptyline/adverse effects/*therapeutic use ; Antidepressive Agents, Tricyclic/adverse effects/*therapeutic use ; Bruxism/*drug therapy ; Electromyography ; Humans ; Masseter Muscle/*drug effects/physiopathology ; Patient Selection ; }, } @article {pmid11462908, year = {2001}, author = {Komura, K and Masuda, H and Esumi, M}, title = {Distinct relationship between polypoid growth type and sporadic colorectal carcinomas with microsatellite instability.}, journal = {Hepato-gastroenterology}, volume = {48}, number = {39}, pages = {706-710}, pmid = {11462908}, issn = {0172-6390}, mesh = {Adult ; Aged ; Aged, 80 and over ; Alleles ; Colonic Polyps/*genetics/pathology ; Colorectal Neoplasms/*genetics/pathology ; Colorectal Neoplasms, Hereditary Nonpolyposis/*genetics/pathology ; Female ; Humans ; Intestinal Mucosa/pathology ; Male ; Microsatellite Repeats/*genetics ; Middle Aged ; Minisatellite Repeats ; Neoplasm Invasiveness ; Protein Serine-Threonine Kinases ; Receptor, Transforming Growth Factor-beta Type II ; Receptors, Transforming Growth Factor beta/genetics ; }, abstract = {BACKGROUND/AIMS: This study was carried out to clarify whether colorectal carcinomas with MSI (microsatellite instability) is correlated with growth types of invasive carcinomas.

METHODOLOGY: Samples of tumor tissue and adjacent normal mucosa were obtained from 45 patients with sporadic advanced colorectal cancer. The MSI was assessed by the mobility shift assay of microsatellite and VNTR (variable numbers of tandem repeat) alleles using 12 markers. Tumors with four or more positive loci were determined to be MSI positive. The polyadenine tract (A)10 of the third exon in TGF beta RII was also assessed by mobility shift assay of DNA fragments amplified with primers. Histological examination was performed to divide all tumors into polypoid growth carcinoma and nonpolypoid growth carcinoma, according to Shimoda et al.'s classification.

RESULTS: Ten of 11 cases with MSI had a 1-base pair deletion in a polyadenine tract in the TGF beta RII gene. Fifteen cases showed polypoid growth and 30 cases indicated nonpolypoid growth. There were 9 polypoid growth cases and 2 nonpolypoid growth cases with MSI, while there were 6 polypoid growth cases and 28 nonpolypoid growth cases without MSI. Colorectal cancer cases with MSI had a significantly higher incidence of cases with polypoid growth (9/11) compared to those without MSI (6/34) (P = 0.0004).

CONCLUSIONS: Sporadic colorectal carcinomas with MSI tend to show a polypoid growth type. We think that there are two types including "adenoma-carcinoma sequence" type and "RER" type in colorectal carcinomas that show adenoma-carcinoma progression.}, } @article {pmid11459158, year = {2001}, author = {Soproni, K and Miklósi, A and Topál, J and Csányi, V}, title = {Comprehension of human communicative signs in pet dogs (Canis familiaris).}, journal = {Journal of comparative psychology (Washington, D.C. : 1983)}, volume = {115}, number = {2}, pages = {122-126}, doi = {10.1037/0735-7036.115.2.122}, pmid = {11459158}, issn = {0735-7036}, mesh = {Animals ; *Behavior, Animal ; Choice Behavior ; Dogs/*psychology ; Female ; Humans ; Male ; Nonverbal Communication/*psychology ; *Recognition, Psychology ; *Social Behavior ; }, abstract = {On the basis of a study by D. J. Povinelli, D. T. Bierschwale, and C. G. Cech (1999), the performance of family dogs (Canis familiaris) was examined in a 2-way food choice task in which 4 types of directional cues were given by the experimenter: pointing and gazing, head-nodding ("at target"), head turning above the correct container ("above target"), and glancing only ("eyes only"). The results showed that the performance of the dogs resembled more closely that of the children in D. J. Povinelli et al.'s study, in contrast to the chimpanzees' performance in the same study. It seems that dogs, like children, interpret the test situation as being a form of communication. The hypothesis is that this similarity is attributable to the social experience and acquired social routines in dogs because they spend more time in close contact with humans than apes do, and as a result dogs are probably more experienced in the recognition of human gestures.}, } @article {pmid11446148, year = {2001}, author = {Benichou, J}, title = {A review of adjusted estimators of attributable risk.}, journal = {Statistical methods in medical research}, volume = {10}, number = {3}, pages = {195-216}, doi = {10.1177/096228020101000303}, pmid = {11446148}, issn = {0962-2802}, mesh = {*Algorithms ; Epidemiologic Methods ; Epidemiologic Studies ; Humans ; Risk Assessment/*methods ; }, abstract = {This paper reviews adjusted methods of estimation of attributable risk (AR), that is methods that allow one to obtain estimates of AR while controlling for other factors. Estimability and basic principles of AR estimation are first considered and the rationale for adjusted AR estimators is discussed. Then, adjusted AR estimators are reviewed focusing on cross-sectional, cohort and case-control studies. Two inconsistent adjusted estimators are briefly commented upon. Next, adjusted estimators based on stratification, namely the weighted-sum and Mantel-Haenszel (MH) approaches, are reviewed and contrasted. It appears that the weighted-sum approach, which allows for full interaction between exposure and adjustment factors, can be affected by small-sample bias. By contrast, the MH approach, which rests on the assumption of no interaction between exposure and adjustment factors may be misleading if interaction between exposure and adjustment factors is present. Model-based adjusted estimators represent a more general and flexible approach that includes both stratification approaches as special cases and offers intermediate options. Bruzzi et al.'s and Greenland and Drescher's estimators are reviewed and contrasted. Finally, special problems of adjusted estimation are considered, namely estimation from case-cohort data, estimation for risk factors with multiple levels, for multiple risk factors, for recurrent events, estimation of the prevented and preventable fractions, and estimation of the generalized impact fraction. Comments on future directions are presented.}, } @article {pmid11424644, year = {2001}, author = {Donk, M}, title = {Illusory conjunctions die hard: a reply to Prinzmetal, Diedrichsen, and Ivry (2001).}, journal = {Journal of experimental psychology. Human perception and performance}, volume = {27}, number = {3}, pages = {542-546}, pmid = {11424644}, issn = {0096-1523}, mesh = {Association Learning ; Attention ; *Color Perception ; Humans ; Mental Recall ; *Optical Illusions ; *Pattern Recognition, Visual ; Psychophysics ; *Reading ; }, abstract = {M. Donk (1999) showed that various data patterns that have been considered as evidence for the existence of illusory conjunctions may be due to errors of target-nontarget confusion, an account that challenges the mere existence of illusory conjunction. In a reply, W. Prinzmetal, J. Diedrichsen, and R. B. Ivry (2001) argued against this conclusion, claiming that some earlier findings can be explained only when one assumes that illusory conjunctions exist. The current article shows that Prinzmetal et al.'s claims cannot refute any of Donk's earlier conclusions, suggesting indeed that one can only conclude that "illusory conjunctions are an illusion."}, } @article {pmid11419223, year = {2000}, author = {Ling, LE and Grabe, E and Nolan, F}, title = {Quantitative characterizations of speech rhythm: syllable-timing in Singapore English.}, journal = {Language and speech}, volume = {43}, number = {Pt 4}, pages = {377-401}, doi = {10.1177/00238309000430040301}, pmid = {11419223}, issn = {0023-8309}, mesh = {Adult ; Female ; Humans ; Male ; *Multilingualism ; Phonetics ; Singapore ; *Speech Acoustics ; Speech Production Measurement ; Time Factors ; United Kingdom ; }, abstract = {British English and Singapore English are said to differ in rhythmic patterning. British English is commonly described as stress-timed, but Singapore English is claimed to be syllable-timed. In the present paper, we explore the acoustic nature of the suggested cross-varietal difference. In directly comparable samples from British English and Singapore English, two types of acoustic measurements were taken; we calculated a variability index reflecting changes in vowel length over utterances, and measurements reflecting vowel quality. Our findings provide acoustic data which support the hypothesized cross-varietal difference in rhythmic patterning; we show (1) that successive vowel durations are more nearly equal in Singapore English than in British English, and (2) that reduced vowels pattern more peripherally in the F1/F2 formant space in Singapore English than in British English. We complete the paper with a comparison of our vowel variability index with a set of acoustic measures for rhythm proposed by Ramus, Nespor, and Mehler (1999), which focus on variability in vocalic and intervocalic intervals. We conclude that our variability index is more successful in capturing rhythmic differences than Ramus et al. (1999)'s measures, and that an application of our index to Ramus et al.'s intervocalic measure may provide a further diagnostic of rhythmic class.}, } @article {pmid11417143, year = {2001}, author = {Calandrino, JG and Kurtz, RM and Strube, MJ}, title = {Efficacy of induction and difficulty level in durability of post-hypnotic suggestions.}, journal = {The American journal of clinical hypnosis}, volume = {44}, number = {1}, pages = {13-25}, doi = {10.1080/00029157.2001.10403452}, pmid = {11417143}, issn = {0002-9157}, mesh = {Adult ; Female ; Follow-Up Studies ; Humans ; Hypnosis/*methods ; Male ; *Suggestion ; Treatment Outcome ; }, abstract = {We examined whether participants instructed to reenter a hypnotic state as part of the post-hypnotic suggestion (PHS) show less decay in responding over an 8-week period than participants who do not receive such instructions. We also attempted to replicate Trussell, Kurtz, and Strube's (1996) finding on impact of difficulty level of suggestion on response curve. Fifty-nine highly susceptible participants were selected by the Stanford Hypnotic Susceptibility Scale: Form C (SHSS:C) and were assigned to one of four groups (two levels of Difficulty [easy-hard] x two levels of Condition [hypnotic PHS, non-hypnotic PHS]). Participants were tested for PHS at 1, 3, 6, and 8 weeks. A 2 x 2 x 4 (Difficulty x Condition x Time) factorial ANOVA was conducted, with Time as a repeated-measure. The outcome variable at each time was either pass or fail for relevant suggestion. None of the effects containing Condition as a term were significant indicating there is no advantage to using Berrigan, Kurtz, Stabile, and Strube's (1991) atypical induction technique to influence the durability of PHS. We found a significant Time effect but failed to replicate Trussell et al.'s findings for Difficulty level. The differing results found in these three recent studies (Berrigan et al., Trussell et al., and the current study) suggest the effects for durability of PHS may be quite fragile in spite of rigorous experimental controls used in all three studies.}, } @article {pmid11410056, year = {2001}, author = {Feuston, BP and Miller, MD and Culberson, JC and Nachbar, RB and Kearsley, SK}, title = {Comparison of knowledge-based and distance geometry approaches for generation of molecular conformations.}, journal = {Journal of chemical information and computer sciences}, volume = {41}, number = {3}, pages = {754-763}, doi = {10.1021/ci000464g}, pmid = {11410056}, issn = {0095-2338}, mesh = {Algorithms ; *Artificial Intelligence ; Crystallography, X-Ray ; *Molecular Conformation ; Pattern Recognition, Automated ; Quantitative Structure-Activity Relationship ; }, abstract = {A knowledge-based approach for generating conformations of molecules has been developed. The method described here provides a good sampling of the molecule's conformational space by restricting the generated conformations to those consistent with the reference database. The present approach, internally named et for enumerate torsions, differs from previous database-mining approaches by employing a library of much larger substructures while treating open chains, rings, and combinations of chains and rings in the same manner. In addition to knowledge in the form of observed torsion angles, some knowledge from the medicinal chemist is captured in the form of which substructures are identified. The knowledge-based approach is compared to Blaney et al.'s distance geometry (DG) algorithm for sampling the conformational space of molecules. The structures of 113 protein-bound molecules, determined by X-ray crystallography, were used to compare the methods. The present knowledge-based approach (i) generates conformations closer to the experimentally determined conformation, (ii) generates them sooner, and (iii) is significantly faster than the DG method.}, } @article {pmid11405315, year = {2001}, author = {McGue, M and Christensen, K}, title = {The heritability of cognitive functioning in very old adults: evidence from Danish twins aged 75 years and older.}, journal = {Psychology and aging}, volume = {16}, number = {2}, pages = {272-280}, doi = {10.1037//0882-7974.16.2.272}, pmid = {11405315}, issn = {0882-7974}, mesh = {Age Factors ; Aged ; Aged, 80 and over ; Aging/*genetics/psychology ; *Cognition ; Cognition Disorders/*genetics ; Denmark ; Female ; Genetic Predisposition to Disease ; Humans ; Male ; Neuropsychological Tests ; Sex Factors ; Twins, Dizygotic/genetics/*psychology ; Twins, Monozygotic/genetics/*psychology ; }, abstract = {Heritable influences on cognitive functioning were investigated in a sample of 403 pairs of like-sex Danish twins aged 75 years and older. Twins completed the Mini-Mental State Examination and 3 other cognitive tests. Genetic factors accounted for 26-54% of the variance on these measures, with the balance being due to environmental factors that create differences rather than similarities among reared-together relatives. Deleting twins with severe cognitive impairment had little effect on the results, indicating that the heritability of cognitive functioning was not due entirely to genes affecting dementia. Neither age nor gender moderated twin similarity, and differential social contact could not account for correlation differences between monozygotic and dizygotic twins. These results replicate G. E. McClearn et al.'s (1997) study in indicating substantial genetic influences on late-life cognitive functioning.}, } @article {pmid11352604, year = {2001}, author = {Mayhew, J and Johnston, D and Martindale, J and Jones, M and Berwick, J and Zheng, Y}, title = {Increased oxygen consumption following activation of brain: theoretical footnotes using spectroscopic data from barrel cortex.}, journal = {NeuroImage}, volume = {13}, number = {6 Pt 1}, pages = {975-987}, doi = {10.1006/nimg.2001.0807}, pmid = {11352604}, issn = {1053-8119}, mesh = {Animals ; Blood Volume/physiology ; Brain Mapping ; Carbon Dioxide/blood ; Diffusion ; Hemoglobins/metabolism ; *Laser-Doppler Flowmetry ; *Magnetic Resonance Spectroscopy ; Numerical Analysis, Computer-Assisted ; Oxygen Consumption/*physiology ; Oxyhemoglobins/metabolism ; Rats ; Regional Blood Flow/physiology ; Somatosensory Cortex/*blood supply ; }, abstract = {Optical imaging spectroscopy (OIS) and laser Doppler flowmetry (LDF) data sequences from anesthetized rats were used to determine the relationship between changes in oxy-and deoxygenated hemoglobin concentration and changes in blood volume and flow in the presence and absence of stimulation. The data from Jones et al. (accompanying paper) were used to explore the differences between two theoretical models of flow activation coupling. The essential difference between the two models is the extension of the model of Buxton and Frank by Hyder et al. (1998, J. Appl. Physiol. 85: 554--564) to incorporate change in capillary diffusivity coupled to flow. In both models activation-increased flow changes increase oxygen transport from the capillary; however, in Hyder et al.'s model the diffusivity of the capillary itself is increased. Hyder et al. proposed a parameter (Omega), a scaling "constant" linking increased blood flow and oxygen "diffusivity" in the capillary bed. Thus, in Buxton and Frank's theory, Omega = 0; i.e., there are no changes in diffusivity. In Hyder et al.'s theory, 0 < Omega < 1, and changes in diffusivity are assumed to be linearly related to flow changes. We elaborate the theoretical position of both models to show that, in principle, the different predictions from the two theories can be evaluated using optical imaging spectroscopy data. We find that both theoretical positions have limitations when applied to data from brief stimulation and when applied to data from mild hypercapnia. In summary, the analysis showed that although Hyder et al.'s proposal that diffusivity increased during activation did occur; it was shown to arise from an implementation of Buxton and Frank's theory under episodes of brief stimulation. The results also showed that the scaling parameter Omega is not a constant as the Hyder et al. model entails but in fact varies over the time course of the flow changes. Data from experiments in which mild hypercapnia was administered also indicated changes in the diffusivity of the capillary bed, but in this case the changes were negative; i.e., oxygen transport from the capillary decreased relative to baseline under hypercapnia. Neither of the models could account for the differences between the hypercapnia and activation data when matched for equivalent flow changes. A modification to the models to allow non-null tissue oxygen concentrations that can be moderated by changes due to increased metabolic demand following increased neural activity is proposed. This modification would allow modulation of oxygen transport from the capillary bed (e.g., changes in diffusivity) by tissue oxygen tension and would allow a degree of decoupling of flow and oxygen delivery, which can encompass both the data from stimulation and from hypercapnia.}, } @article {pmid11348851, year = {2001}, author = {Takahashi, K and Iwata, K and Matsumoto, M and Matsumoto, H and Nakao, K and Hatahara, T and Ohta, Y and Kanai, K and Maruo, H and Baba, K and Hijikata, M and Mishiro, S}, title = {Hepatitis C virus (HCV) genotype 1b sequences from fifteen patients with hepatocellular carcinoma: the 'progression score' revisited.}, journal = {Hepatology research : the official journal of the Japan Society of Hepatology}, volume = {20}, number = {2}, pages = {161-171}, doi = {10.1016/s1386-6346(00)00141-8}, pmid = {11348851}, issn = {1386-6346}, abstract = {The genome of hepatitis C virus (HCV) associated with hepatocellular carcinoma (HCC) may have some characteristics which would barely be found in those of HCV from asymptomatic carriers (ASC). We analyzed 15 HCC patients who were infected with HCV genotype 1b (HCV-1b) for complete nucleotide sequences of the viral genomes. Of the 15 isolates, three were sequenced up to the first nucleotide of the 5'UTR, and six were sequenced to encompass the X-tail at the 3' end: sequencing of at least three-quarters of the 5'UTR and entire polyprotein-ORF was accomplished in all 15 isolates. Analyses of these sequences together with those reported previously by Nagayama et al. [Hepatology; 31 (2000) 745] suggested that nine residues (nt 119 of 5'UTR and aa 90, 434, 938, 962, 1176, 1412, 2143, and 2774 of polyprotein) might be useful to discriminate HCC-type sequences from ASC-type ones. The 'progression score' was 1.4+/-0.9 in ASC versus 3.7+/-1.5 in HCC (P=3.87E-07) when calculated with the Nagayama et al.'s seven residues, but was 1.4+/-0.6 versus 4.6+/-1.9 (P=1.33E-09) with our nine residues: a greater difference between HCC and ASC was achieved in the latter system. Further analyses, by increasing the sample size and/or by extending the comparison to include entire 5'UTR and 3'UTR/X-tail, may thus contribute to define the 'progression score' more appropriately.}, } @article {pmid11318631, year = {2001}, author = {Ouwerkerk, R and Bottomley, PA}, title = {On neglecting chemical exchange when correcting in vivo (31)P MRS data for partial saturation: commentary on: "Pitfalls in the measurement of metabolite concentrations using the one-pulse experiment in in Vivo NMR".}, journal = {Journal of magnetic resonance (San Diego, Calif. : 1997)}, volume = {149}, number = {2}, pages = {282-286}, doi = {10.1006/jmre.2001.2286}, pmid = {11318631}, issn = {1090-7807}, support = {1 HL56882-01/HL/NHLBI NIH HHS/United States ; R01-HL61912-01/HL/NHLBI NIH HHS/United States ; R21 HL62332-01/HL/NHLBI NIH HHS/United States ; }, mesh = {Adenosine Triphosphate/metabolism ; Animals ; Humans ; Magnetic Resonance Spectroscopy/*methods ; Myocardial Ischemia/metabolism ; Myocardium/*metabolism ; Phosphates/metabolism ; Phosphocreatine/metabolism ; Phosphorus/*analysis ; }, abstract = {This article replies to Spencer et al. (J. Magn. Reson. 149, 251--257, 2001) concerning the degree to which chemical exchange affects partial saturation corrections using saturation factors. Considering the important case of in vivo (31)P NMR, we employ differential analysis to demonstrate a broad range of experimental conditions over which chemical exchange minimally affects saturation factors, and near-optimum signal-to-noise ratio is preserved. The analysis contradicts Spencer et al.'s broad claim that chemical exchange results in a strong dependence of saturation factors upon M(0)'s and T(1) and exchange parameters. For Spencer et al.'s example of a dynamic (31)P NMR experiment in which phosphocreatine varies 20-fold, we show that our strategy of measuring saturation factors at the start and end of the study reduces errors in saturation corrections to 2% for the high-energy phosphates.}, } @article {pmid11316374, year = {2001}, author = {Caudill, BD and Harding, WM and Moore, BA}, title = {DWI prevention: profiles of drinkers who use designated drivers.}, journal = {Addictive behaviors}, volume = {26}, number = {2}, pages = {155-166}, doi = {10.1016/s0306-4603(00)00097-6}, pmid = {11316374}, issn = {0306-4603}, support = {1-R01-AA10729/AA/NIAAA NIH HHS/United States ; }, mesh = {Adult ; *Alcohol Drinking ; Alcoholic Intoxication/*prevention & control/*psychology ; *Automobile Driving ; Demography ; Female ; Humans ; Logistic Models ; Male ; Middle Aged ; Surveys and Questionnaires ; }, abstract = {The effectiveness of designated driver (DD) use in preventing driving while intoxicated (DWI) depends on whether drinkers at risk for DWI use DDs. Bivariate and logistic regression analyses conducted on data from 1,391 Computer-Assisted Telephone Interviews (CATIs) and from 902 barroom patron surveys showed that DD users, compared to nonusers, tended to be at-risk, heavier drinkers. For example, logistic regression using the CATI sample indicated that DD users were more likely to drink more often outside the home, to achieve higher blood alcohol concentrations (BACs) when drinking outside the home, to ride with intoxicated drivers (RID), and to be heavy drinkers on D. Cahalan et al.'s (1969) Quantity-Frequency-Variability (QFV) index. Similarly, logistic regression using the barroom sample showed that DD users tended to be heavy drinkers on the QFV index, and were more likely to drive after drinking and to ride with intoxicated drivers. Additional analyses showed that DD users also were more likely than nonusers to engage in other behavior to avoid DWI, such as drinking less, waiting to drive until the effects of alcohol diminish, walking home, and staying overnight. These results are consistent with other findings from a related study by the current authors which showed that at-risk drinkers also used free safe (taxi) rides to avoid DWI, however were still more likely to report DWI and RID behavior (B. D. Caudill, W. M. Harding, & B. Moore, in press). Consequently, DWI prevention efforts may be improved by future research aimed at learning why such at-risk drinkers sometimes take steps to avoid DWI and sometimes do not.}, } @article {pmid11308876, year = {2001}, author = {Abkarian, M and Lartigue, C and Viallat, A}, title = {Motion of phospholipidic vesicles along an inclined plane: sliding and rolling.}, journal = {Physical review. E, Statistical, nonlinear, and soft matter physics}, volume = {63}, number = {4 Pt 1}, pages = {041906}, doi = {10.1103/PhysRevE.63.041906}, pmid = {11308876}, issn = {1539-3755}, mesh = {Animals ; Biophysics/*methods ; Cattle ; Chickens ; Eggs ; Models, Statistical ; Phosphatidylcholines/chemistry ; Phospholipids/*chemistry ; Serum Albumin/chemistry ; Surface Properties ; Time Factors ; }, abstract = {The migration of giant phospholipidic vesicles along an inclined plane in a quiescent fluid was observed as a function of the mass and the radius R of the vesicles, and as a function of the angle of inclination of the plane. Vesicles were swollen, and did not adhere to the substrate surface. It was observed from a side-view chamber that they have quasispherical shapes. The vesicles mainly slide along the plane, but also roll. The ratio omegaR/v of rotational to translational velocities is of the order of 0.15 for vesicles of radius ranging from 10 to 30 microm. Values of this ratio, and variations of v versus R, are well described by Goldman et al.'s model developed for the motion of rigid spheres close to a wall [Chem. Eng. Sci. 22, 637 (1967)]. In this framework, the thickness of the fluid film between the vesicle and the substrate derived from fitting experimental data was found to be equal to 48 nm.}, } @article {pmid11302266, year = {2001}, author = {Devilly, GJ and Foa, EB}, title = {The investigation of exposure and cognitive therapy: comment on Tarrier et al (1999).}, journal = {Journal of consulting and clinical psychology}, volume = {69}, number = {1}, pages = {114-116}, doi = {10.1037//0022-006x.69.1.114}, pmid = {11302266}, issn = {0022-006X}, mesh = {Clinical Trials as Topic ; *Cognitive Behavioral Therapy ; Data Interpretation, Statistical ; Humans ; *Imagery, Psychotherapy ; Stress Disorders, Post-Traumatic/*psychology/*therapy ; }, abstract = {This article outlines concerns relating to the N. Tarrier et al. (1999) investigation comparing imaginal exposure and cognitive therapy. Specifically, the authors offer N. Tarrier et al. the opportunity to operationally define and clarify the claim that more patients treated by imaginal exposure "worsened" during treatment. Equally, in light of N. Tarrier et al.'s low effect sizes in relation to past research the authors also highlight the need to utilize accountable treatment integrity checks.}, } @article {pmid11280474, year = {2001}, author = {Belsky, J and Friedman, SL and Hsieh, KH}, title = {Testing a core emotion-regulation prediction: does early attentional persistence moderate the effect of infant negative emotionality on later development?.}, journal = {Child development}, volume = {72}, number = {1}, pages = {123-133}, doi = {10.1111/1467-8624.00269}, pmid = {11280474}, issn = {0009-3920}, support = {U10-HD25420/HD/NICHD NIH HHS/United States ; }, mesh = {*Affect ; Age Factors ; *Attention ; Child Behavior/*physiology ; Child Development/physiology ; Child, Preschool ; Forecasting ; Humans ; Infant ; Longitudinal Studies ; Problem Solving ; Psychology, Child ; *Social Perception ; }, abstract = {To test the hypothesis that early attentional persistence will moderate the effect of infant negative emotionality on social competence, problem behavior, and school readiness at age 3, data collected as part of the NICHD Study of Early Child Care were subject to structural equation modeling analyses (N = 1,038). Consistent with Eisenberg et al.'s data on older children, high levels of negative emotionality were associated with low levels of social competence only when attentional persistence was poor. No such moderating effects of attentional persistence emerged in the case of behavior problems. And in the case of school readiness, findings indicated that high levels of negative emotionality predicted high levels of school readiness when attentional persistence was high, a result opposite to that found with respect to the prediction of social competence.}, } @article {pmid11274982, year = {2001}, author = {Caramazza, A and Costa, A}, title = {Set size and repetition in the picture--word interference paradigm: implications for models of naming.}, journal = {Cognition}, volume = {80}, number = {3}, pages = {291-298}, doi = {10.1016/s0010-0277(00)00137-2}, pmid = {11274982}, issn = {0010-0277}, support = {DC04542/DC/NIDCD NIH HHS/United States ; }, mesh = {Humans ; *Memory ; Periodicity ; *Semantics ; Speech/physiology ; *Verbal Behavior ; Visual Perception/physiology ; *Vocabulary ; }, abstract = {Caramazza and Costa (Cognition 75 (2000) B51) reported results which demonstrate that a semantically related word distractor interferes in picture naming even when it is not in the response set and there is no possibility for mediated interference. They interpreted the results to be problematic for the model of lexical access proposed by Levelt, Roelofs, and Meyer (Behavioral and Brain Sciences 22 (1999) 1). Roelofs (Cognition 80 (2001, this issue 283--90)) argues that those results are not inconsistent with Levelt et al.'s model when certain new assumptions about the mechanism of lexical selection are considered. Here we show that even with these assumptions the model still makes the wrong predictions. We report new results which demonstrate that the semantic interference and facilitation effects that are obtained respectively in the basic-level and category-level naming variants of the picture-word interference paradigm are not the result of response set size and response repetitions.}, } @article {pmid11246938, year = {2001}, author = {Morley, J and Rosner, AL and Redwood, D}, title = {A case study of misrepresentation of the scientific literature: recent reviews of chiropractic.}, journal = {Journal of alternative and complementary medicine (New York, N.Y.)}, volume = {7}, number = {1}, pages = {65-78; discussion 79-82}, doi = {10.1089/107555301300004547}, pmid = {11246938}, issn = {1075-5535}, mesh = {Chiropractic/*standards ; Humans ; *Peer Review ; *Prejudice ; }, abstract = {Accurate use of published data and references is a cornerstone of the peer-review process. Statements, inferences, and conclusions based upon these references should logically ensue from the data they contain. When journal articles and textbook chapters summarizing the safety and efficacy of particular therapies or interventions use references inaccurately or with apparent intent to mislead, the integrity of scientific reporting is fundamentally compromised. Ernst et al.'s publication on chiropractic include repeated misuse of references, misleading statements, highly selective use of certain published papers, failure to refer to relevant literature, inaccurate reporting of the contents of published work, and errors in citation. Meticulous analysis of some influential negative reviews has been carried out to determine the objectivity of the data reported. The misrepresentation that became evident deserves full debate and raises serious questions about the integrity of the peer-review process and the nature of academic misconduct.}, } @article {pmid11226621, year = {2001}, author = {Wu, H}, title = {An improved surface-based method for DNA computation.}, journal = {Bio Systems}, volume = {59}, number = {1}, pages = {1-5}, doi = {10.1016/s0303-2647(00)00133-7}, pmid = {11226621}, issn = {0303-2647}, mesh = {*Computing Methodologies ; *DNA ; Optics and Photonics ; }, abstract = {DNA computing is a novel method for solving a class of intractable computational problems, in which the computing time can grow exponentially with problem size. Up to now, many accomplishments have been achieved to improve its performance and increase its reliability, among which a surface-based method is an efficient candidate. In this paper, the surface-based approach proposed by Liu, Q., Wang, L., Frutos, A.G., Condon, A.E., Corn, R.M., and Smith, L.M., 2000, DNA computing on surfaces. Nature 403, 175-179 is analyzed and an improved surface-based method for DNA computation (i.e. the hybrid DNA/optical computing method) is proposed. Compared with Liu et al.'s approach, our method has some significant advantages such as low cost, short operating time, reusable surface and simple experimental steps. Moreover, the concept of combining easily patterned DNA computing steps with equally parallel, but generally uniform and not easily patterned optical computing steps is an important new direction.}, } @article {pmid11223802, year = {2001}, author = {Hunt, PS and Holloway, JL and Scordalakes, EM}, title = {Social interaction with an intoxicated sibling can result in increased intake of ethanol by periadolescent rats.}, journal = {Developmental psychobiology}, volume = {38}, number = {2}, pages = {101-109}, doi = {10.1002/1098-2302(200103)38:2<101::aid-dev1002>3.0.co;2-4}, pmid = {11223802}, issn = {0012-1630}, support = {AA12135/AA/NIAAA NIH HHS/United States ; AA12466/AA/NIAAA NIH HHS/United States ; }, mesh = {Age Factors ; Alcoholic Intoxication/*psychology ; Animals ; Behavior, Animal/*drug effects ; Central Nervous System Depressants/*pharmacology ; Ethanol/*pharmacology ; Female ; Male ; Rats ; Rats, Sprague-Dawley ; *Sibling Relations ; *Social Behavior ; }, abstract = {A novel procedure for enhancing voluntary intake of ethanol in periadolescent rats is described. The procedure is a modification of Galef et al.'s (e.g., Galef, Kennett, & Stein, 1985; Anim Learn Behave 13:25-30) demonstrator-observer procedure. Subjects were Sprague-Dawley rats, 28-35 days of age. The experimental subject (observer) interacted with a same-sex conspecific (demonstrator) previously administered (a) 1.5 g/kg ethanol, (b) an equal volume of water, or (c) 2.1% Sanka coffee intragastrically. Observers were tested with 24-hour access to ethanol and coffee solutions. Observers that had interacted with demonstrators administered ethanol ingested significantly more ethanol during the test than observers in the other two groups. In Experiment 2 demonstrators were administered one of several doses of ethanol (0.0, 1.0, 1.5, or 3.0 g/kg) and observers' ethanol intakes were assessed. Only those observers that interacted with 1.5 g/kg demonstrators increased their ingestion of ethanol, relative to water controls. The lower (1.0 g/kg) and higher (3.0 g/kg) dose groups did not show altered ethanol ingestion. These results are discussed with respect to threshold levels of respired ethanol cues and the ability of observers to detect these cues from demonstrators. The demonstrator-observer procedure appears to be effective for the social transmission of preferences for ethanol in periadolescent rats.}, } @article {pmid11211996, year = {2000}, author = {Preston, RJ}, title = {Response to Klaunig J.E. et al.'s "Epigenetic mechanisms of chemical carcinogenesis".}, journal = {Human & experimental toxicology}, volume = {19}, number = {10}, pages = {569-70; discussion 571-2}, doi = {10.1191/096032700701546497}, pmid = {11211996}, issn = {0960-3271}, mesh = {Animals ; Carcinogens/*toxicity ; Humans ; Neoplasms/*chemically induced/*genetics ; }, } @article {pmid11202989, year = {2000}, author = {Beezer, AE}, title = {Comments on Serger et al.'s (1998, 1999) calorimetric stability studies.}, journal = {International journal of pharmaceutics}, volume = {207}, number = {1-2}, pages = {117-118}, doi = {10.1016/s0378-5173(00)00524-x}, pmid = {11202989}, issn = {0378-5173}, mesh = {Calorimetry ; *Drug Stability ; }, } @article {pmid11195315, year = {2000}, author = {El Miedany, YM and Mehanna, AN and El Baddini, MA}, title = {Altered bone mineral metabolism in patients with osteoarthritis.}, journal = {Joint bone spine}, volume = {67}, number = {6}, pages = {521-527}, doi = {10.1016/s1297-319x(00)00218-9}, pmid = {11195315}, issn = {1297-319X}, mesh = {Biomarkers/analysis ; Bone Density/*physiology ; Bone and Bones/diagnostic imaging/*metabolism/physiopathology ; Female ; Humans ; Lumbar Vertebrae/diagnostic imaging/metabolism/physiopathology ; Male ; Middle Aged ; Osteoarthritis/*metabolism/physiopathology ; Radiography ; Sex Factors ; }, abstract = {OBJECTIVE: Investigation of the relationship between osteoarthritis (OA) and mineral density, and determination of any alteration in bone mineral, metabolism as assessed by biochemical markers of bone resorption and formation.

METHODS: Forty females and 20 males were included in the study. Spinal OA as well as knee OA were defined from radiographs and graded according to Lane et al.'s and Spector et al.'s scoring systems. Bone mineral density (BMD) of the lumbar spine was measured by osteo CT. Bone turnover rates were estimated by measuring biochemical markers of bone resorption (urinary deoxypyridinoline) and bone formation (bone-specific alkaline phosphatase). Forty females and 20 males of the same age were studied as a control group.

RESULTS: BMD was greater in women with spinal OA as compared to controls (P < 0.05). Also, males with OA had a non-significantly higher BMD than controls. The bone resorption markers were higher than normal values. However, they were lower than the control group. Similarly, the bone formation markers were lower as compared to the control group.

CONCLUSION: Spinal OA is associated with higher BMD. This protective effect of spinal OA against osteoporosis may be mediated through decreased rate of bone turnover.}, } @article {pmid11194254, year = {2000}, author = {Wynn, K}, title = {Findings of addition and subtraction in infants are robust and consistent: reply to Wakeley, Rivera, and Langer.}, journal = {Child development}, volume = {71}, number = {6}, pages = {1535-6; discussion 1537-9}, doi = {10.1111/1467-8624.00245}, pmid = {11194254}, issn = {0009-3920}, mesh = {Attention ; Concept Formation ; Female ; Humans ; Infant ; Male ; *Mathematics ; *Problem Solving ; *Psychology, Child ; }, abstract = {Findings showing numerical computation abilities in infants are considerably more robust and consistent than Wakeley, Rivera, and Langer suggest. All the interim replication attempts have successfully replicated my original findings. Possible reasons for Wakeley et al.'s failure to replicate are discussed.}, } @article {pmid11186904, year = {2000}, author = {Nishii, T and Hirata, A and Masaki, T and Kaida, K and Nakamura, R and Motoyoshi, K and Kamakura, K}, title = {[Reduced signal intensity of T2 weighted MR imaging of thalamus and putamen in multiple sclerosis in Japan].}, journal = {Rinsho shinkeigaku = Clinical neurology}, volume = {40}, number = {7}, pages = {677-682}, pmid = {11186904}, issn = {0009-918X}, mesh = {Adolescent ; Adult ; Asian People ; Demyelinating Diseases/pathology ; Disability Evaluation ; Female ; Ferritins/metabolism ; Humans ; Iron/metabolism ; Japan ; *Magnetic Resonance Imaging ; Male ; Middle Aged ; Multiple Sclerosis/diagnosis/metabolism/*pathology ; Putamen/metabolism/*pathology ; Thalamus/metabolism/*pathology ; United States ; }, abstract = {Although studies using magnetic resonance imaging (MRI) in multiple sclerosis (MS) patients have focused on findings in the white matter because of its demyelination pathogenesis, Drayer et al. have reported a high incidence of low signal intensity on T2 weighted MR imaging (MRI) in gray matter such as the thalamus and putamen. In Japan there has been no investigation of MRI findings of the basal ganglia in MS patients. Therefore, we attempted to examine the incidence and clinical significance of the imaging phenomenon in 34 Japanese patients with MS (12 male, 22 female, ages 18-54 years). As it is well known that the spinal cord and optic nerves are more frequently involved in MS than the brain in Japanese patients, we divided the patients into two subgroups based on their clinical features and the major sites of demyelination on MRI. One group included the 17 patients whose demyelinations occurred in the brain (brain-type), and the other group included the 17 patients whose abnormalities were found in the spinal cord with or without optic nerve involvement (non-brain type). As a control, MRI studies were also performed in age-matched patients with headache without any neurological signs. On T2 weighted MRI, decreased signal intensity in the thalamus was found in only four patients with MS, 11.8% of the total number examined, and in the putamen in three patients with MS, 8.8% of the total examined. All of the patients who showed abnormal decreased signal intensity in the thalamus and/or putamen belonged to the brain-type group, and these incidences were 23.5% in the thalamus and 17.6% in the putamen among the brain-type patients. No patient belonging to the non-brain type showed this imaging sign. This imaging sign was well correlated with the degree of white matter abnormalities in the brain estimated as a score according to modified Callanan et al.'s method. In addition, this sign was also correlated with the expanded disability status scales (EDSS) in the brain-type patients. These observations suggest that the axonal damages due to severe demyelination may induce the impaired transport of iron resulting in an accumulation of ferritin in the thalamus and putamen, and would cause decreased signal intensity on T2 weighted MRI. The relatively low incidence of decreased signal intensity in the thalamus and putamen in this study may be associated with differences in the clinical phenotype of MS between Japan and the USA. In brain-type patients the evaluation of basal ganglia on T2 weighted MRI may be a useful tool for estimating patients' disabilities.}, } @article {pmid11180470, year = {2000}, author = {Heinik, J and Reider-Groswasser, II and Solomesh, I and Segev, Y and Bleich, A}, title = {Clock drawing test: correlation with linear measurements of CT studies in demented patients.}, journal = {International journal of geriatric psychiatry}, volume = {15}, number = {12}, pages = {1130-1137}, doi = {10.1002/1099-1166(200012)15:12<1130::aid-gps259>3.0.co;2-n}, pmid = {11180470}, issn = {0885-6230}, mesh = {Aged ; Aged, 80 and over ; *Art ; Atrophy ; Caudate Nucleus/diagnostic imaging/*pathology ; Cognition ; Dementia/complications/diagnosis/*psychology ; Female ; Humans ; Male ; Mental Status Schedule ; Motor Skills ; Predictive Value of Tests ; Regression Analysis ; *Tomography, X-Ray Computed ; Visual Perception ; }, abstract = {OBJECTIVES: To investigate a presumed correlation between clock drawing ratings and linear measurements of computerized tomography (CT) studies in demented patients.

DESIGN: Blinded evaluations of clock drawing tests and CT studies of elderly dementia patients were conducted by a geriatric psychiatrist and a neuroradiologist.

SUBJECTS: Fifty-one community-dwelling elderly subjects meeting the criteria for DSM-IV diagnosis of dementia (Alzheimer's type dementia: N=31; vascular dementia: N=15; "mixed" type dementia: N=5).

MATERIALS: Mini-Mental State Examination (MMSE), Cambridge Cognitive Examination (CAMCOG), Clinical Dementia Rating (CDR). CAMCOG derived scored clock drawings were evaluated using adaptations of Shulman et al.'s and Freedman et al.'s methods. CT studies were evaluated using six different linear measurements of brain atrophy described in the literature.

RESULTS: Of the CT linear measurements, only the Cerebro-Ventricular Index-2 (CVI-2; bicaudate index) significantly correlated with clock drawing ratings (CAMCOG's clock r=-0.407, p=0.003; Shulman's method r=0.357, p=0.01, Freedman's method r=-0.413, p=0.003) in the dementia group. There was no significant correlation between CVI-2 with demographic (age), cognitive (MMSE, CAMCOG) and clinical (duration of illness, CDR) ratings. Alzheimer's patients generally maintained a significant correlation between CVI-2 and clock drawings, but vascular dementia patients did not; CVI-2 also correlated significantly with the Praxis subtest of the CAMCOG in dementia and Alzheimer's patients but not in the vascular dementia group. Similarly, multiple stepwise regression analysis showed that only CVI-2 but not the other radiological measures studied, was selected as the significant variable to correlated with clock drawing test ratings in the dementia group and Alzheimer's patients. Partial correlation analysis controlling for demographic and clinical variables shows that controlled variables had no significant effect on the relationship between clock drawing ratings and CVI-2.

CONCLUSION: A single and easy to perform measure of caudate atrophy correlates specifically and consistently with impairments revealed in the clock drawing test and with a Praxis subtest, suggesting possible caudate involvement with clock drawings in dementia in general and of the Alzheimer's type in particular.}, } @article {pmid11175606, year = {2000}, author = {Reichenheim, ME and Moraes, CL and Hasselmann, MH}, title = {[Semantic equivalence of the Portuguese version of the Abuse Assessment Screen tool used for the screening of violence against pregnant women].}, journal = {Revista de saude publica}, volume = {34}, number = {6}, pages = {610-616}, doi = {10.1590/s0034-89102000000600008}, pmid = {11175606}, issn = {0034-8910}, mesh = {*Battered Women/psychology ; *Domestic Violence ; Female ; Humans ; *Pregnancy/psychology ; *Research Design ; Semantics ; *Surveys and Questionnaires ; }, abstract = {INTRODUCTION: Research programs and actions regarding family violence have been growing steadily. Therefore, there's a need to develop data collection tools. In Brazil, further problems come up since tools that have been developed elsewhere need to be adapted and translated. This study focuses on the Abuse Assessment Screening (AAS) used to detect violence against pregnant women. The objective is to evaluate the semantic equivalence between the original tool in English and two Portuguese versions, and propose a synthetic version to be used in the field.

METHODS: The evaluation of semantic equivalence was carried out in 4 steps: (1) translation, (2) back translation, (3) formal appreciation of equivalence and (4) a final critical assessment by family violence experts.

RESULTS: Translation, back translation and the steps 3 and 4 assessment are presented for each item of the tool, along with the original in English. The text covers each discussion that led to the final version. Both versions were quite similar in 14 out of 15 items. Nevertheless, the second version showed to be slightly more adequate although for some items the decision was to combine both versions or, in one case, use an item from version 1.

CONCLUSION: The procedure undertaken in this study is discussed in the light of Herdman et al.'s proposal (1998) regarding transcultural equivalence. The study also stresses the importance of using more than one version in the process and the appropriateness of including an additional step about the assessment of the target population's understanding of the tool.}, } @article {pmid11164326, year = {2001}, author = {Holmström, I and Rosenqvist, U}, title = {A change of the physicians' understanding of the encounter parallels competence development.}, journal = {Patient education and counseling}, volume = {42}, number = {3}, pages = {271-278}, doi = {10.1016/s0738-3991(00)00132-4}, pmid = {11164326}, issn = {0738-3991}, mesh = {Adult ; Aged ; Diabetes Mellitus/therapy ; *Education, Medical, Continuing ; Female ; Humans ; Male ; Middle Aged ; *Physician-Patient Relations ; Physicians/*psychology ; *Self Concept ; Sweden ; Videotape Recording ; }, abstract = {Patients today complain that physicians do not listen. There is a need to improve the professional competence in the patient encounter. According to theory, competence is a result of how people perceive their work. Observation and reflection can improve the competence. The aim of this study was to investigate if physicians can develop a more patient-centred consultation style by an experienced-based specialist course and how such a development is related to the physicians understanding of the task. The physicians video recorded consultations and reflected on these. The video consultations were analysed with a time study and Pendleton et al.'s consultation schedule [Pendleton D, Schoefield T, Tate P, Havelock P. The consultation: an approach to learning and teaching. Oxford: Oxford University Press, 1984.]. Before-after questions were answered. The study indicates that seven out of 10 physicians participating in the course had developed a patient-centred attitude and acted according to it. The time study gave ambiguous results. This study implicates that it is possible to initiate competence development by influencing the understanding of the encounter.}, } @article {pmid11153794, year = {2000}, author = {McWilliams, LA and Cox, BJ and Enns, MW}, title = {Impact of adult attachment styles on pain and disability associated with arthritis in a nationally representative sample.}, journal = {The Clinical journal of pain}, volume = {16}, number = {4}, pages = {360-364}, doi = {10.1097/00002508-200012000-00014}, pmid = {11153794}, issn = {0749-8047}, mesh = {Adaptation, Psychological ; Adolescent ; Adult ; Anxiety/psychology ; Arthritis/complications/*epidemiology/*psychology ; Canada/epidemiology ; Comorbidity ; Cross-Sectional Studies ; Depression/psychology ; *Disability Evaluation ; Humans ; Middle Aged ; *Object Attachment ; Pain/*epidemiology/etiology/*psychology ; Predictive Value of Tests ; Psychological Tests ; Regression Analysis ; }, abstract = {OBJECTIVE: The objective of this study was to evaluate Mikail et al.'s hypothesis that adult attachment styles are associated with important pain-related variables such as pain and disability levels.

DESIGN: A cross-sectional design was used to examine the relation between measures of adult attachment styles and both pain and disability.

SETTING: The data used were obtained from the National Comorbidity Survey, a large and nationally representative sample of community-dwelling individuals aged 15 to 54 years. In the present study, individuals (n = 381) in the National Comorbidity Survey with arthritis or related conditions were included.

OUTCOME MEASURES: Ratings regarding three adult attachment styles (secure, anxious, and avoidant) were obtained by administering Hazan and Shaver's attachment self-report in an interview format. Pain and disability were assessed in a similar manner using four-point rating scales.

RESULTS: Ratings of insecure attachment were positively and significantly correlated with both pain and disability. A multiple regression analysis revealed that pain severity and the rating of anxious attachment could account for 20.3% of the variance in disability.

CONCLUSIONS: The attachment theory holds promise for understanding reactions to pain conditions, and Mikail et al.'s model warrants further investigation.}, } @article {pmid11142862, year = {2000}, author = {Redington, M}, title = {Not evidence for separable controlled and automatic influences in artificial grammar learning: comment on Higham, Vokey, and Pritchard (2000).}, journal = {Journal of experimental psychology. General}, volume = {129}, number = {4}, pages = {471-475}, doi = {10.1037//0096-3445.129.4.471}, pmid = {11142862}, issn = {0096-3445}, mesh = {Humans ; Knowledge ; *Learning ; *Linguistics ; Mental Processes ; Reproducibility of Results ; Unconscious, Psychology ; }, abstract = {P. A. Higham, J. R. Vokey, and J. L. Pritchard (2000) claimed to provide evidence for separable controlled and automatic processes in artificial grammar learning. It is argued that their results are compatible with a single controlled influence: Participants might mistakenly identify more grammatical items than nongrammatical items as belonging to the other grammar, because the grammars are very similar to each other, and the nongrammatical items are relatively highly dissimilar. Participants' knowledge may be ambiguous, rather than automatic. It is further argued that even if Higham et al.'s data do support automatic effects, opposition logic, in this case, cannot be said to have succeeded where dissociation logic has failed, because it is used to address the issue of whether participants have conscious control over the knowledge they acquire, rather than whether they possess conscious awareness of that knowledge.}, } @article {pmid11135353, year = {2001}, author = {Spiegelman, D and Carroll, RJ and Kipnis, V}, title = {Efficient regression calibration for logistic regression in main study/internal validation study designs with an imperfect reference instrument.}, journal = {Statistics in medicine}, volume = {20}, number = {1}, pages = {139-160}, doi = {10.1002/1097-0258(20010115)20:1<139::aid-sim644>3.0.co;2-k}, pmid = {11135353}, issn = {0277-6715}, support = {CA50597/CA/NCI NIH HHS/United States ; CA57030/CA/NCI NIH HHS/United States ; CA74112/CA/NCI NIH HHS/United States ; ES09411/ES/NIEHS NIH HHS/United States ; P30-ES09106/ES/NIEHS NIH HHS/United States ; }, mesh = {Adult ; Antineoplastic Agents/adverse effects ; Breast Neoplasms/epidemiology ; Dietary Supplements ; Epidemiologic Factors ; Female ; Humans ; Incidence ; Likelihood Functions ; Linear Models ; *Logistic Models ; Middle Aged ; Multivariate Analysis ; Occupational Exposure/adverse effects ; Pharmacists ; Prospective Studies ; Reproducibility of Results ; *Research Design ; Vitamin A ; }, abstract = {An extension to the version of the regression calibration estimator proposed by Rosner et al. for logistic and other generalized linear regression models is given for main study/internal validation study designs. This estimator combines the information about the parameter of interest contained in the internal validation study with Rosner et al.'s regression calibration estimate, using a generalized inverse-variance weighted average. It is shown that the validation study selection model can be ignored as long as this model is jointly independent of the outcome and the incompletely observed covariates, conditional, at most, upon the surrogates and other completely observed covariates. In an extensive simulation study designed to follow a complex, multivariate setting in nutritional epidemiology, it is shown that with validation study sizes of 340 or more, this estimator appears to be asymptotically optimal in the sense that it is nearly unbiased and nearly as efficient as a properly specified maximum likelihood estimator. A modification to the regression calibration variance estimator which replaces the standard uncorrected logistic regression coefficient variance with the sandwich estimator to account for the possible misspecification of the logistic regression fit to the surrogate covariates in the main study, was also studied in this same simulation experiment. In this study, the alternative variance formula yielded results virtually identical to the original formula. A version of the proposed estimator is also derived for the case where the reference instrument, available only in the validation study, is imperfect but unbiased at the individual level and contains error that is uncorrelated with other covariates and with error in the surrogate instrument. Replicate measures are obtained in a subset of study participants. In this case it is shown that the validation study selection model can be ignored when sampling into the validation study depends, at most, only upon perfectly measured covariates. Two data sets, a study of fever in relation to occupational exposure to antineoplastics among hospital pharmacists and a study of breast cancer incidence in relation to dietary intakes of alcohol and vitamin A, adjusted for total energy intake, from the Nurses' Health Study, were analysed using these new methods. In these data, because the validation studies contained less than 200 observations and the events of interest were relatively rare, as is typical, the potential improvements offered by this new estimator were not apparent.}, } @article {pmid11133407, year = {2000}, author = {Wartenberg, D and Reyner, D}, title = {TCE Meta-Analyses: Wartenberg et al.'s Response.}, journal = {Environmental health perspectives}, volume = {108}, number = {12}, pages = {A543-A544}, pmid = {11133407}, issn = {1552-9924}, abstract = {Comments on Trichloroethylene and Cancer: Epidemiologic Evidence by Daniel Wartenberg, Daniel Reyner, and Cheryl Siegel Scott. Environ Health Perspect 108(suppl 2):161-176 (2000).}, } @article {pmid11131815, year = {2000}, author = {Hanley, JR and Turner, JM}, title = {Why are familiar-only experiences more frequent for voices than for faces?.}, journal = {The Quarterly journal of experimental psychology. A, Human experimental psychology}, volume = {53}, number = {4}, pages = {1105-1116}, doi = {10.1080/713755942}, pmid = {11131815}, issn = {0272-4987}, mesh = {Adolescent ; Adult ; Association Learning ; Attention ; Discrimination Learning ; *Face ; Female ; Humans ; Male ; *Mental Recall ; Perceptual Distortion ; *Voice ; }, abstract = {Hanley, Smith, and Hadfield (1998) showed that when participants were asked to recognize famous people from hearing their voice, there was a relatively large number of trials in which the celebrity's voice was felt to be familiar but biographical information about the person could not be retrieved. When a face was found familiar, however, the celebrity's occupation was significantly more likely to be recalled. This finding is consistent with the view that it is much more difficult to associate biographical information with voices than with faces. Nevertheless, recognition level was much lower for voices than for faces in Hanley et al.'s study, and participants made significantly more false alarms in the voice condition. In the present study, recognition performance in the face condition was brought down to the same level as recognition in the voice condition by presenting the faces out of focus. Under these circumstances, it proved just as difficult to recall the occupations of faces found familiar as it was to recall the occupations of voices found familiar. In other words, there was an equally large number of familiar-only responses when faces were presented out of focus as in the voice condition. It is argued that these results provide no support for the view that it is relatively difficult to associate biographical information with a person's voice. It is suggested instead that associative connections between processing units at different levels in the voice-processing system are much weaker than is the case with the corresponding units in the face-processing system. This will reduce the recall of occupations from voices even when the voice has been found familiar. A simulation was performed using the latest version of the IAC model of person recognition (Burton, Bruce, & Hancock, 1999) which demonstrated that the model can readily accommodate the pattern of results obtained in this study.}, } @article {pmid11129353, year = {2000}, author = {Boyles, SH and Ness, RB and Grisso, JA and Markovic, N and Bromberger, J and CiFelli, D}, title = {Life event stress and the association with spontaneous abortion in gravid women at an urban emergency department.}, journal = {Health psychology : official journal of the Division of Health Psychology, American Psychological Association}, volume = {19}, number = {6}, pages = {510-514}, doi = {10.1037//0278-6133.19.6.510}, pmid = {11129353}, issn = {0278-6133}, mesh = {Abortion, Spontaneous/*epidemiology/genetics/psychology ; Adolescent ; Adult ; Case-Control Studies ; Congenital Abnormalities ; Female ; Gestational Age ; Humans ; *Life Change Events ; Odds Ratio ; Pennsylvania/epidemiology ; Pregnancy ; Risk ; Stress, Psychological/*complications ; }, abstract = {In this study, the authors hypothesized that life event stress is associated with an increased risk of spontaneous abortion. Using a nested case-control design in an emergency department (N = 970), stress was measured using a life event inventory and a sample drawn from R. B. Ness et al.'s (1999) Early Pregnancy Study. Gestational age at time of fetal loss served as a marker of chromosomal status. Women experiencing more than one life event used more alcohol and public assistance. Spontaneous abortion at 11 weeks or greater was associated with more life event stress (adjusted odds ratio 2.9, 95% confidence interval 1.4-6.2), whereas spontaneous abortion at any gestational age was not, implying that life event stress increases the risk of chromosomally normal spontaneous abortion. An analysis of confounders showed tobacco use was associated with an increased risk of spontaneous abortion, whereas prenatal care was only associated with fetal loss at 11 weeks or greater.}, } @article {pmid11109622, year = {2000}, author = {Kiseleva, NM and Shubin, SV}, title = {[Differential diagnosis of chronic urogenic arthritis].}, journal = {Terapevticheskii arkhiv}, volume = {72}, number = {5}, pages = {52-55}, pmid = {11109622}, issn = {0040-3660}, mesh = {Adult ; Arthritis/*diagnosis/etiology ; Arthritis, Psoriatic/diagnosis ; Chronic Disease ; Diagnosis, Differential ; Humans ; Lymphadenitis/complications/diagnosis ; Severity of Illness Index ; Spondylitis, Ankylosing/diagnosis ; Urologic Diseases/*complications ; }, abstract = {AIM: To investigate features of chronic urogenic arthritis (CUA) and its differences with psoriatic arthritis (PA) and ankylosing spondylarthritis (AS) with joint lesion.

MATERIALS AND METHODS: CUA, AS, PA were diagnosed according to S. M. Sidelnikova et al., S. van der Linden and Agababova, respectively, in 94 patients. The disease ran for more than 3 years. Articular syndrome was examined in CUA, AS and PA.

RESULTS: Articular syndrome in CUA remains for the most part monoarticular with affection of the joints of the low extremities. AS has clinical and x-ray signs of sacroileitis, affection of the spinal column and hip joints. PA runs with multiple arthritic lesions of the hand and foot joints.

CONCLUSIONS: Chronic infection persists in all the CUA and PA patients. Its exacerbation coincides with arthritis aggravations. Only in CUA there is a chronological connection between acute or aggravated chronic urogenital infection and initial symptoms of joint disease.}, } @article {pmid11108084, year = {2000}, author = {Lebra, TS}, title = {New insight and old dilemma: a cross-cultural comparison of Japan and the United States.}, journal = {Child development}, volume = {71}, number = {5}, pages = {1147-1149}, doi = {10.1111/1467-8624.00216}, pmid = {11108084}, issn = {0009-3920}, mesh = {Child ; *Child Development ; Cross-Cultural Comparison ; *Cultural Characteristics ; Humans ; Individuality ; *Intergenerational Relations ; Japan ; Models, Psychological ; *Object Attachment ; United States ; }, abstract = {Conflict in close relationships, or "generative tension," characterizes both the United States and Japan, with differences only in the style and timing of its manifestation. The potentially fruitful strategy of Rothbaum et al.'s article is constrained by their cross-cultural comparative methodology.}, } @article {pmid11100918, year = {2000}, author = {Heubeck, BG}, title = {Cross-cultural generalizability of CBCL syndromes across three continents: from the USA and Holland to Australia.}, journal = {Journal of abnormal child psychology}, volume = {28}, number = {5}, pages = {439-450}, pmid = {11100918}, issn = {0091-0627}, mesh = {Adolescent ; Aggression/psychology ; Australia ; Child ; Child Behavior Disorders/*diagnosis/*psychology ; Child, Preschool ; Cross-Cultural Comparison ; *Cultural Characteristics ; Factor Analysis, Statistical ; Female ; Humans ; Juvenile Delinquency/psychology ; Male ; Models, Psychological ; Netherlands ; Psychiatric Status Rating Scales/*standards/statistics & numerical data ; Reproducibility of Results ; United States ; }, abstract = {The study asked how well Achenbach's 8-factor cross-informant model for the Child Behavior Check-list (Achenbach, 1991a, 1991b, 1991c) fits clinic data in the USA, Holland, and Australia. DeGroot et al.'s Dutch 8-factor model (DeGroot, Koot, & Verhulst 1994) was also tested for its cross-cultural generalizability. Achenbach's matched clinical sample data (N = 2110) were analyzed and contrasted with the previously reported Dutch findings (N = 2335), as well as a new data set collected on clinic referred children and adolescents in Australia (N = 2237). Confirmatory factor analyses supported the Dutch as much as the American model in the USA, Holland, and Australia. Although about 90% of items showed convergent validity across models and countries, the attention and especially the social problems factor found least support. Most double loadings in the current models were not upheld. Instead, additional analyses discovered a number of unmodelled loadings including many cross-loadings. This led to the redefinition of the social problems factor as a mean aggression factor (with associated social problems) whereas the original aggression factor focuses on emotional acting out and the delinquent factor describes an evasive, covert type of antisocial behavior. Overall most support was obtained for the withdrawn, somatic, anxious/depressed, thought problems, and aggressive factors.}, } @article {pmid11086590, year = {2000}, author = {D'Alessandro, M and Lester, D}, title = {Self-destructiveness and manic-depressive tendencies.}, journal = {Psychological reports}, volume = {87}, number = {2}, pages = {466}, doi = {10.2466/pr0.2000.87.2.466}, pmid = {11086590}, issn = {0033-2941}, mesh = {Adult ; Bipolar Disorder/complications/epidemiology/*psychology ; Female ; Humans ; Male ; Self-Injurious Behavior/complications/epidemiology/*psychology ; Surveys and Questionnaires ; }, abstract = {In a sample of 72 undergraduates, scores on Thalbourne, et al.'s measure of manic and depressive tendencies were associated with those on one of general self-destructive tendencies.}, } @article {pmid11082856, year = {2000}, author = {Marí-Beffa, P and Estévez, AF and Danziger, S}, title = {Stroop interference and negative priming: problems with inferences from null results.}, journal = {Psychonomic bulletin & review}, volume = {7}, number = {3}, pages = {499-503}, pmid = {11082856}, issn = {1069-9384}, mesh = {Adult ; Analysis of Variance ; *Attention ; *Cognition ; Color ; *Cues ; Female ; Humans ; *Inhibition, Psychological ; Male ; Neuropsychological Tests ; Reaction Time ; Recognition, Psychology ; }, abstract = {The Stroop color-naming effect has often been taken as evidence for the automaticity of word processing (MacLeod, 1991). Recently, Besner, Stolz, and Boutilier (1997) reported that coloring a single letter instead of the whole word eliminated the Stroop effect. From this finding, they concluded that word processing could not be purely automatic, since it can be prevented. We asked whether the elimination of the Stroop effect is sufficient evidence for concluding that the word is not processed. Combining Besner et al.'s manipulation with a negative-priming procedure, we found intact negative priming from the prime color word in the absence of a Stroop effect. This result clearly indicates that the meaning of the prime word was processed. The findings highlight the importance of using converging methods to evaluate lack of processing.}, } @article {pmid11060754, year = {2000}, author = {Alarcón, GS}, title = {Tetracyclines for the treatment of rheumatoid arthritis.}, journal = {Expert opinion on investigational drugs}, volume = {9}, number = {7}, pages = {1491-1498}, doi = {10.1517/13543784.9.7.1491}, pmid = {11060754}, issn = {1354-3784}, mesh = {Animals ; Arthritis, Rheumatoid/*drug therapy/immunology ; Humans ; Tetracyclines/*therapeutic use ; }, abstract = {In this review the rationale for the possible beneficial effect of tetracycline derivatives for the treatment of rheumatoid arthritis is discussed. Early studies (Sanchez, Skinner et al. and Brown et al.) and the two open trials of the 1980s are briefly discussed. The three double-blind studies conducted in the 1990s (Kloppenburg et al. , The Netherlands; the MIRA trial, USA and the O'Dell et al., USA) are described in detail. The baseline clinical and demographic data for these patients, as well as the efficacy and toxicity data are described in the text and summarised in tables. The long-term data of the O'Dell et al.'s trial is described. Finally, side effects not observed during the conduct of these trials, but reported to occur in other patients, for example those receiving minocycline for the treatment of acne, are also listed.}, } @article {pmid11056849, year = {2000}, author = {Willmott, C and Anderson, V and Anderson, P}, title = {Attention following pediatric head injury: a developmental perspective.}, journal = {Developmental neuropsychology}, volume = {17}, number = {3}, pages = {361-379}, doi = {10.1207/S15326942DN1703_5}, pmid = {11056849}, issn = {8756-5641}, mesh = {Attention/*physiology ; Child ; Child Behavior Disorders/diagnosis/*etiology ; Cognition Disorders/diagnosis/etiology ; Female ; Head Injuries, Closed/*complications/*physiopathology ; Humans ; Male ; Neuropsychological Tests ; Severity of Illness Index ; }, abstract = {This study investigated the relations between age at injury (AAI) and attentional functioning, and intellectual and academic achievement following pediatric head injury. The theoretical framework of attention proposed by Mirsky, Anthony, Duncan, Ahern, and Kellam (1991) provided the basis for this analysis, and the profile of attention found in uninjured children was evaluated for this sample. Thirty-three moderately head-injured individuals were recruited, with AAI ranging from 1 to 12 years. First, the development of attentional skills in this closed head injury (CHI) sample was found to be comparable to that of Mirsky et al.'s model. Second, AAI did not predict outcome and appeared not to be associated with the finding of mildly delayed acquisition of spelling and arithmetic skills. Also, AAI did not predict the behavioral symptoms of inattention present in this sample as indicated by parental report. It may be that AAI only influences development following severe CHI in which there is permanent cerebral pathology.}, } @article {pmid11039656, year = {2000}, author = {Baldari, C and Guidetti, L}, title = {A simple method for individual anaerobic threshold as predictor of max lactate steady state.}, journal = {Medicine and science in sports and exercise}, volume = {32}, number = {10}, pages = {1798-1802}, doi = {10.1097/00005768-200010000-00022}, pmid = {11039656}, issn = {0195-9131}, mesh = {Adolescent ; Adult ; *Anaerobic Threshold ; Exercise Test ; *Exercise Tolerance ; Female ; Humans ; Lactic Acid/*blood ; Male ; Predictive Value of Tests ; Sports ; }, abstract = {BACKGROUND: The individual anaerobic threshold (IAT) is defined (18) as the highest metabolic rate where blood lactate (La) concentrations are maintained at a steady-state during prolonged exercise. Stegmann et al.'s (18) method to detect IAT, using La-performance relationship during incremental graded exercise, is based on the assumption that La is in relatively steady state by the end of each 3-min stage of work rate. However, at the end of a 3-min stage, an La steady state (Lass) is not reached (13).

PURPOSE: The present study was designed to investigate whether the IAT should be determined by attributing La value to the antecedent stage (IATa) or to the same stage of its measurement (IATm), then to verify whether this IAT would be a valid indicator of the max Lass during prolonged exercise.

METHODS: Forty-one athletes (21 male and 20 female), regularly involved in different physical training, performed three exercise tests on treadmill. The first one was a 3-min stage incremental test to detect the IATa and IATm. The other two tests were 30-min prolonged tests at the IATa and IATm workload. Lass were present in IATa intensity (about 4.0 mmol x L(-1)) both in male and female athletes, whereas at IATm intensity a Lass was not present and a premature break-off occurred in some cases.

DISCUSSION: This protocol can be useful for practical use because: 1) the method of choosing the anaerobic threshold is easy to apply; 2) it does not require to reach the maximal effort; and 3) although in some cases the IATa could probably underestimate the workload of max Lass, the IATa can be regarded as guideline to define the intensity of endurance training.}, } @article {pmid11028150, year = {2000}, author = {Vickers, A}, title = {The literature search for Bloom et al.'s review.}, journal = {International journal of technology assessment in health care}, volume = {16}, number = {3}, pages = {944}, doi = {10.1017/s0266462300102211}, pmid = {11028150}, issn = {0266-4623}, mesh = {*Complementary Therapies ; Humans ; *Randomized Controlled Trials as Topic ; }, } @article {pmid11027113, year = {2000}, author = {Hanson, RK and Nicholaichuk, T}, title = {A cautionary note regarding Nicholaichuk et al. (2000).}, journal = {Sexual abuse : a journal of research and treatment}, volume = {12}, number = {4}, pages = {289-293}, doi = {10.1177/107906320001200405}, pmid = {11027113}, issn = {1079-0632}, mesh = {Humans ; Male ; Recurrence ; Sex Offenses/*prevention & control/statistics & numerical data ; Treatment Outcome ; }, abstract = {The treatment outcome study by Nicholaichuk, Gordon, Gu, and Wong (2000) used a novel method for identifying a comparison group of untreated sex offenders (i.e., drawing from existing criminal history records). A potential problem with their approach is that older records would be expected to include a disproportionate numbers of recidivists. Such an artifact is identified in Nicholaichuk et al.'s (2000) study; nevertheless, their data continue to suggest a small, positive effect for treatment even after eliminating the cases in which bias is most likely.}, } @article {pmid11026421, year = {2000}, author = {Muenz, TA and Cole, JC and Balderson, A}, title = {Written expression, Hooper, and blind rating.}, journal = {Psychological reports}, volume = {87}, number = {1}, pages = {255-258}, doi = {10.2466/pr0.2000.87.1.255}, pmid = {11026421}, issn = {0033-2941}, mesh = {*Achievement ; Attention ; Child ; *Creativity ; Female ; Humans ; Male ; *Visual Perception ; *Writing ; }, abstract = {Much research has supported the assertion of Hooper, et al.'s 1994 claims that specific stimuli perform better than others in eliciting well-developed written responses; however, previous research was conducted with raters who were aware of the hypotheses. The present study of 29 middle school children validated previous support for Hooper, et al.'s assertions by implementing blind rating and, once again, finding that significant differences between Hooper-like and non-Hooper-like prompts existed for structural items but not for items of mechanics.}, } @article {pmid11017720, year = {2000}, author = {de Ribaupierre, A and Bailleux, C}, title = {The development of working memory: further note on the comparability of two models of working memory.}, journal = {Journal of experimental child psychology}, volume = {77}, number = {2}, pages = {110-127}, doi = {10.1006/jecp.2000.2591}, pmid = {11017720}, issn = {0022-0965}, mesh = {Adult ; Child ; *Child Development ; Child, Preschool ; Female ; Humans ; Male ; *Mental Recall ; Models, Psychological ; Orientation ; Pattern Recognition, Visual ; Psychomotor Performance ; }, abstract = {This paper is a set of reflections on Kemps, De Rammelaere, and Desmet's article (2000, this issue), in which the two models by Baddeley and Pascual-Leone are compared. First, some of the similarities and differences between the two models which we identified in a 1994 paper (de Ribaupierre & Bailleux, 1994) are briefly summarized and reexamined in the light of more recent work. Second, we debate the issue of whether each model makes a specific contribution to the explanation of some of Kemps et al.'s results, that is, of whether they can be considered to be complementary. Third, we argue for the necessity of theoretical task analyses, in view of the divergent results obtained in the two tasks used (the Corsi and the Peanut tasks), notably different developmental profiles, and an overall higher level of performance in the Corsi task. Finally, we briefly summarize a very similar study in which we also used Mr. Peanut with concurrent tasks in children and in young adults and in which we obtained rather different results. By comparing the experimental procedures used in the two studies, we contribute some exploratory hypotheses, while raising issues that can easily be generalized to other visuo-spatial working memory tasks.}, } @article {pmid11012361, year = {2000}, author = {Blackwell, M}, title = {Evolution. Terrestrial life--fungal from the start?.}, journal = {Science (New York, N.Y.)}, volume = {289}, number = {5486}, pages = {1884-1885}, doi = {10.1126/science.289.5486.1884}, pmid = {11012361}, issn = {0036-8075}, mesh = {*Biological Evolution ; Fossils ; Fungi/*physiology ; Plants/microbiology ; }, abstract = {Fungi have been implicated in the early colonization of land by plants. As Blackwell explains in her Perspective, Redecker et al.'s discovery of a fossil fungus provides strong support for this hypothesis. The important role of symbiotic associations of fungi with plants and animals is increasingly being recognized, as is the fact that some of these associations date back to the origin of terrestrial life on Earth.}, } @article {pmid11004871, year = {2000}, author = {Hsu, LM}, title = {Effects of directionality of significance tests on the bias of accessible effect sizes.}, journal = {Psychological methods}, volume = {5}, number = {3}, pages = {333-342}, doi = {10.1037/1082-989x.5.3.333}, pmid = {11004871}, issn = {1082-989X}, mesh = {*Bias ; *Data Interpretation, Statistical ; Humans ; *Meta-Analysis as Topic ; Models, Statistical ; Outcome Assessment, Health Care/statistics & numerical data ; *Psychometrics ; Psychotherapy/statistics & numerical data ; }, abstract = {The proportion of studies that use one-tailed statistical significance tests (pi) in a population of studies targeted by a meta-analysis can affect the bias of the sample effect sizes (sample ESs, or ds) that are accessible to the meta-analyst. H. C. Kraemer, C. Gardner, J. O. Brooks, and J. A. Yesavage (1998) found that, assuming pi = 1.0, for small studies (small Ns) the overestimation bias was large for small population ESs (delta < or = 0.2) and reached a maximum for the smallest population ES (viz., delta = 0). The present article shows (with a minor modification of H. C. Kraemer et al.'s model) that when pi = 0, the small-N bias of accessible sample ESs is relatively small for delta < or = 0.2, and a minimum (in fact, nonexistent) for delta = 0. Implications are discussed for interpretations of meta-analyses of (a) therapy efficacy and therapy effectiveness studies, (b) comparative outcome studies, and (c) studies targeting small but important population ESs.}, } @article {pmid10995609, year = {2000}, author = {Fincher, RM and Simpson, DE and Mennin, SP and Rosenfeld, GC and Rothman, A and McGrew, MC and Hansen, PA and Mazmanian, PE and Turnbull, JM}, title = {Scholarship in teaching: an imperative for the 21st century.}, journal = {Academic medicine : journal of the Association of American Medical Colleges}, volume = {75}, number = {9}, pages = {887-894}, doi = {10.1097/00001888-200009000-00009}, pmid = {10995609}, issn = {1040-2446}, mesh = {Education, Medical ; *Faculty, Medical ; *Schools, Medical ; Teaching/*standards ; }, abstract = {At some medical schools broader definitions of scholarship have emerged along with corresponding changes in their academic reward systems. Such situations are not common, however. The definition of scholarship generally applied by medical schools is unnecessarily narrow and excludes areas of legitimate academic activity and productivity that are vital to the fulfillment of the school's educational mission. The authors maintain that creative teaching with effectiveness that is rigorously substantiated, educational leadership with results that are demonstrable and broadly felt, and educational methods that advance learners' knowledge are consistent with the traditional definition of scholarship. Faculty whose educational activities fulfill the criteria above are scholars and must be recognized by promotion. The authors specifically address scholarship in education, focusing on teaching and other learning-related activities rather than on educational research, which may be assessed and rewarded using the same forms of evidence as basic science or clinical research. They build on Boyer's work, which provides a vocabulary for discussing the assumptions and values that underlie the roles of faculty as academicians. Next, they apply Glassick et al.'s criteria for judging scholarly work to faculty members' educational activities to establish a basis for recognition and reward consistent with those given for other forms of scholarship. Finally, the authors outline the organizational infrastructure needed to support scholars in education.}, } @article {pmid10979548, year = {2000}, author = {Jankowicz, E and Drozdowski, W and Halicka, D}, title = {[Frontotemporal dementias].}, journal = {Neurologia i neurochirurgia polska}, volume = {34}, number = {3}, pages = {553-564}, pmid = {10979548}, issn = {0028-3843}, mesh = {Amyotrophic Lateral Sclerosis/complications/physiopathology ; Dementia/*diagnosis/etiology/*physiopathology ; Diagnosis, Differential ; Frontal Lobe/*pathology/*physiopathology ; Humans ; Motor Neuron Disease/complications/physiopathology ; Pick Disease of the Brain/physiopathology ; Temporal Lobe/*pathology/*physiopathology ; }, abstract = {Frontotemporal dementias are the second largest degenerative dementia group after Alzheimer's disease. It is a clinical syndrome corresponding to at least three histological entities: Pick's disease, non-specific frontotemporal degeneration, frontal lobe abnormalities associated with motor neuron disease. There are four group of symptoms in the clinical description of FTD: behavioural disorder, affective symptoms, speech disorders, neurological signs. FTD is associated with primary degeneration of the frontal and temporal lobes. Histologically there was neuronal loss, microvacuolation, tau- and ubiquitin-immunoreactive inclusions. The ballooned cortical neurons and tau- and ubiquitin-immunoreactive, argyrophilic inclusions have been called Pick-type histology. There are many descriptions of association of FTD and Pick's disease with motor neuron disease and amyotrophic lateral sclerosis. Histological changes were similar to cortical ones. In this study, we described clinical characteristic features of frontotemporal dementia and difficulties in its identification. The distinctive histopathological pattern in the FTD patients and its value to differentiate frontotemporal degeneration from other degenerative dementias is discussed.}, } @article {pmid10978697, year = {2000}, author = {Verleger, R and Vollmer, C and Wauschkuhn, B and van der Lubbe, RH and Wascher, E}, title = {Dimensional overlap between arrows as cueing stimuli and responses?. Evidence from contra-ipsilateral differences in EEG potentials.}, journal = {Brain research. Cognitive brain research}, volume = {10}, number = {1-2}, pages = {99-109}, doi = {10.1016/s0926-6410(00)00032-x}, pmid = {10978697}, issn = {0926-6410}, mesh = {Adult ; *Cues ; *Electroencephalography ; Electrophysiology ; Female ; Hand/physiology ; Humans ; Male ; Motor Activity/physiology ; Motor Cortex/*physiology ; Photic Stimulation/methods ; Saccades/physiology ; Scalp/*physiology ; }, abstract = {In the S1-S2 interval, 400 ms after an arrow as S1, an EEG-potential difference occurs between scalp sites contralateral and ipsilateral to arrow direction. Eimer [J. Exp. Psychol. Hum. Percept. Perform. 21 (1995) 837-854] interpreted this difference as a sign of automatic activation of the manual response, due to dimensional overlap of arrows and responses. However, according to Kornblum et al.'s [Psychol. Rev. 97 (1990) 253-270] notion of dimensional overlap, responses can only be automatically primed if they are included in the response set. Therefore, participants of the present study had to respond to S2 in separate blocks either by key-press, as in Eimer [J. Exp. Psychol. Hum. Percept. Perform. 21 (1995) 837-854], or by making saccades. In addition, contra-ipsilateral differences were recorded not only from central positions, overlying the hand-motor area, but across the whole scalp. Contralateral negativity at 400 ms after S1 was indeed found over the hand-motor area in the 'hand blocks'. However, this 'L-400' (=lateralization at 400 ms) was generally as large in the 'eye' blocks as in the 'hand' blocks. Therefore, L-400 does not reflect automatic activation of manual responses in the sense of Kornblum et al. [Psychol. Rev. 97 (1990) 253-270]. Further, its topographical maximum was more anterior than the hand-motor-related negativity that preceded the manual response ('LRP') with its maximum at central sites. Therefore, L-400 probably does not originate in the hand-motor cortex. Rather, it may be related to activity of the lateral premotor cortex found in fMRI studies of spatial orienting. The present EEG study extends these studies by delimiting the time period of this activity, suggesting that it reflects encoding of the spatial properties of the arrow for action.}, } @article {pmid10968752, year = {2000}, author = {Kreuter, MW and Sabol, BJ and O'Donovan, A and Donovan, J and Klein, L and Green, LW and Vliet, M and Bradley, T and Campuzano, MK and Tarlov, AR}, title = {Commentaries from grantmakers on Fawcett et al.'s proposed memorandum of collaboration.}, journal = {Public health reports (Washington, D.C. : 1974)}, volume = {115}, number = {2-3}, pages = {180-190}, pmid = {10968752}, issn = {0033-3549}, mesh = {Community Health Planning/economics/organization & administration ; Cooperative Behavior ; Financing, Organized ; Foundations ; Health Care Coalitions/economics/*organization & administration ; Health Promotion/*organization & administration ; Humans ; Interinstitutional Relations ; *Models, Organizational ; Organizational Objectives ; United States ; }, } @article {pmid10950295, year = {2000}, author = {Sutherland, IA}, title = {Relationship between retention, linear velocity and flow for counter-current chromatography.}, journal = {Journal of chromatography. A}, volume = {886}, number = {1-2}, pages = {283-287}, doi = {10.1016/s0021-9673(00)00540-9}, pmid = {10950295}, issn = {0021-9673}, mesh = {Chromatography, Liquid/*methods ; }, abstract = {A recent paper by Du et al. [J. Chromatogr. A, 835 (1999) 231] showed a very good correlation between the retention of stationary phase and the square root of mobile phase flow (F(1/2)) for 12 different phase systems in counter-current chromatography. This paper shows there is a relationship between the above retention and the linear velocity of the mobile phase. In this way, Du et al.'s results can be related to the kinematics of the mobile phase flow in the tubing. This will open the door for further engineering analysis of this fluid dynamic phenomenon.}, } @article {pmid10946588, year = {2000}, author = {Roswarski, TE and Proctor, RW}, title = {Auditory stimulus-response compatibility: is there a contribution of stimulus-hand correspondence?.}, journal = {Psychological research}, volume = {63}, number = {2}, pages = {148-158}, doi = {10.1007/pl00008173}, pmid = {10946588}, issn = {0340-0727}, mesh = {Auditory Perception/*physiology ; Hand/*physiology ; Humans ; Movement/*physiology ; Random Allocation ; Reaction Time ; }, abstract = {Simon, Hinrichs, and Craft found that when subjects responded to a tone in the left or right ear with a left or right keypress, both ear-response-location correspondence and ear-hand correspondence affected reaction time. This outcome is in contrast to results obtained for auditory and visual Simon tasks (i.e., tasks in which stimulus location is irrelevant) as well as results obtained in visual stimulus-response (S-R) compatibility studies, which show only an effect of spatial S-R correspondence. Experiment 1 was a replication of Simon et al.'s experiment in which spatial mapping and hand placement (uncrossed, crossed) were varied. The results were inconsistent with those of Simon et al., showing no ear-hand compatibility effect. Experiment 2 was a second replication with an additional condition examined in which the stimuli were visual locations. The results showed no contribution of stimulus-hand correspondence for either auditory or visual stimuli. Experiment 3 was a replication of another experiment by Simon et al. in which tone pitch was relevant and tone location irrelevant. Like Simon et al.'s data, our results showed no indication that stimulus-hand correspondence is a significant factor. Overall, our results imply that regardless of whether tone location is relevant or irrelevant, ear-response-location correspondence is the only factor that contributes to S-R compatibility in auditory two-choice reaction tasks.}, } @article {pmid10941702, year = {2000}, author = {Meyer, GJ}, title = {On the science of Rorschach research.}, journal = {Journal of personality assessment}, volume = {75}, number = {1}, pages = {46-81}, doi = {10.1207/S15327752JPA7501_6}, pmid = {10941702}, issn = {0022-3891}, mesh = {Female ; Humans ; MMPI ; Male ; Personality Disorders/*diagnosis ; Reproducibility of Results ; *Rorschach Test ; }, abstract = {Wood et al.'s (1999b) article contained several general points that are quite sound. Conducting research with an extreme groups design does produce effect sizes that are larger than those observed in an unselected population. Appropriate control groups are important for any study that wishes to shed light on the characteristics of a targeted experimental group and experimental validity is enhanced when researchers collect data from both groups simultaneously. Diagnostic efficiency statistics--or any summary measures of test validity--should be trusted more when they are drawn from multiple studies conducted by different investigators across numerous settings rather than from a single investigator's work. There should be no question that these points are correct. However, I have pointed out numerous problems with specific aspects of Wood et al.'s (1999b) article. Wood et al. gave improper citations that claimed researchers found or said things that they did not. Wood et al. indicated my data set did not support the incremental validity of the Rorschach over the MMPI-2 when, in fact, my study never reported such an analysis and my data actually reveal that the opposite conclusion is warranted. Wood et al. asserted there was only one proper way to conduct incremental validity analyses even though experts have described how their recommended procedure can lead to significant complications. Wood et al. cited a section of Cohen and Cohen (1983) to bolster their claim that hierarchical and step-wise regression procedures were incompatible and to criticize Burns and Viglione's (1996) regression analysis. However, that section of Cohen and Cohen's text actually contradicted Wood et al.'s argument. Wood et al. tried to convince readers that Burns and Viglione used improper alpha levels and drew improper conclusions from their regression data although Burns and Viglione had followed the research evidence on this topic and the expert recommendations provided in Hosmer and Lemeshow's (1989) classic text. Wood et al. oversimplified issues associated with extreme group research designs and erroneously suggested that diagnostic studies were immune from interpretive confounds that can be associated with this type of design. Wood et al. ignored or dismissed the valid reasons why Burns and Viglione used an extreme groups design, and they never mentioned how Burns and Viglione used a homogeneous sample that actually was likely to find smaller than normal effect sizes. Wood et al. also overlooked the fact that Burns and Viglione identified their results as applying to female nonpatients; they never suggested their findings would characterize those obtained from a clinical sample. Wood et al. criticized composite measures although some of the most important and classic findings in the history of research on personality recommend composite measures as a way to minimize error and maximize validity. Wood et al. also were mistaken about the elements that constitute an optimal composite measure. Wood et al. apparently ignored the factor-analytic evidence that demonstrated how Burns and Viglione created a reasonable composite scale, and Wood et al. similarly ignored the clear evidence that supported the content and criterion related validity of the EMRF. With respect to the HEV, Wood et al. created a z-score formula that used the wrong means and standard deviations. They continued to use this formula despite being informed that it was incorrect. Subsequently, Wood et al. told readers that their faulty z-score formula was "incompatible" with the proper weighted formula and asserted that the two formulas "do not yield identical results" and "do not yield HEV scores that are identical or even very close." These published claims were made even though Wood et al. had seen the results from eight large samples, all of which demonstrated that their wrong formula had correlations greater than .998 with the correct formula. At worst, it seems that Wood et al. (199}, } @article {pmid10941285, year = {2000}, author = {Dell, GS and Schwartz, MF and Martin, N and Saffran, EM and Gagnon, DA}, title = {The role of computational models in neuropsychological investigations of language: reply to Ruml and Caramazza (2000).}, journal = {Psychological review}, volume = {107}, number = {3}, pages = {635-645}, doi = {10.1037/0033-295x.107.3.635}, pmid = {10941285}, issn = {0033-295X}, support = {DC-00191/DC/NIDCD NIH HHS/United States ; }, mesh = {*Aphasia ; Humans ; *Language ; *Models, Psychological ; Neurophysiology ; Reproducibility of Results ; }, abstract = {W. Ruml and A. Caramazza's (2000) analysis of the model of normal and aphasic lexical access proposed by G. S. Dell, M. F. Schwartz, N. Martin, E. M. Saffran, and D. A. Gagnon (1997) is completely at odds with current practice concerning the use of models in psychology. An evaluation of Dell et al.'s original claims using Ruml and Caramazza's model parameters sustains these claims in all respects.}, } @article {pmid10941284, year = {2000}, author = {Ruml, W and Caramazza, A}, title = {An evaluation of a computational model of lexical access: comment on Dell et al. (1997).}, journal = {Psychological review}, volume = {107}, number = {3}, pages = {609-634}, doi = {10.1037/0033-295x.107.3.609}, pmid = {10941284}, issn = {0033-295X}, support = {NS-22201/NS/NINDS NIH HHS/United States ; }, mesh = {*Aphasia ; Cognition ; Humans ; *Language ; *Models, Psychological ; }, abstract = {The computational model of lexical access proposed by G. S. Dell, M. F. Schwartz, N. Martin, E. M. Saffran, and D. A. Gagnon (1997) is evaluated. They argued that fits of their model to naming data obtained from normal and brain-damaged patients support assumptions regarding interactivity in the lexicon, global damage in aphasia, and continuity between normal and aphasic naming behavior. Additional analysis reveals that the model fits the empirical data poorly and that the claims Dell et al. made on the basis of the model's performance would not follow even if the model were accurate. Although use of a novel automatic regression procedure improved the model's fit, it cannot account for 5 of Dell et al.'s 21 patients (24%), and its limitations were found to be inherent in its design. It is argued that claims such as those made by Dell et al. can only be addressed by considering evidence from multiple related tasks and by comparing multiple computational models.}, } @article {pmid10900568, year = {2000}, author = {Leonelli, BT and Chang, CH and Bock, RD and Schilling, SG}, title = {Interpretation of a full-information item-level factor analysis of the MMPI-2: normative sampling and nonpathognomonic descriptors.}, journal = {Journal of personality assessment}, volume = {74}, number = {3}, pages = {400-422}, doi = {10.1207/S15327752JPA7403_5}, pmid = {10900568}, issn = {0022-3891}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Factor Analysis, Statistical ; Humans ; MMPI/*statistics & numerical data ; Middle Aged ; Psychometrics ; Reference Values ; Reproducibility of Results ; }, abstract = {An exploratory item-level full-information factor analysis was performed on the normative sample for the MMPI-2 (Butcher, Dahlstrom, Graham, Tellegen, & Kaemmer, 1989). This method of factor analysis, developed by Schilling and Bock (Bock & Schilling, 1997) and based on item response theory, works directly with the response patterns and avoids the artifacts associated with phi coefficients and tetrachoric coefficients. Promax rotation of the factor solution organizes the clinical scale items into 10 factors that we labeled Distrust, Self-Doubt, Fitness, Serenity, Rebelliousness, Instrumentality, Irritability, Artistry, Sociability, and Self-Reliance. A comparison was made to the results of Johnson, Butcher, Null, and Johnson (1984), who performed a principal-component analysis on an item set of 550 items from the previous version of the MMPI (Hathaway & McKinley, 1943). Along with version changes and sampling differences, the essential differences between Johnson et al.'s results and ours may be attributed to differences between the Schilling and Bock method, which uses all information in the item responses, and the principal-component analysis, which uses the partial information contained in pairwise correlation coefficients. This study included 518 of the complete 567 items of the MMPI-2, versus Johnson et al.'s retention of 309 of the initially included 550 items of the previous MMPI. The full-information analysis retained all 518 initially included items and more evenly distributed the items over the 10 resulting factors, all sharply defined by their highest loading items and easy to interpret. Sampling effects and factor label considerations are discussed, along with recommendations for research that would validate the clinical utility of the implied scales for describing normal personality profiles. The full-information procedure provides for Bayes estimation of scores on these scales.}, } @article {pmid10898877, year = {2000}, author = {Scherrer, SS and Botsis, J and Studer, M and Pini, M and Wiskott, HW and Belser, UC}, title = {Fracture toughness of aged dental composites in combined mode I and mode II loading.}, journal = {Journal of biomedical materials research}, volume = {53}, number = {4}, pages = {362-370}, doi = {10.1002/1097-4636(2000)53:4<362::aid-jbm10>3.0.co;2-s}, pmid = {10898877}, issn = {0021-9304}, mesh = {Aluminum Oxide ; Barium ; *Composite Resins ; Glass Ionomer Cements ; Humans ; Methacrylates ; Silicate Cement ; Silicon Dioxide ; Surface Properties ; }, abstract = {Resin-based laboratory dental composites for prosthetic restorations have been developed in the past years as a cost-effective alternative to conventional porcelain-fused-to-metal or full ceramic restorations. The fracture toughness at different stress states (K(Ic), K(IIc), and mixed-modes K(I), K(II)) was assessed for three laboratory dental composite resins used for prosthetic restorations that were aged up to 12 months in a food simulating fluid (10% ethanol) at 37 degrees C. The materials were mainly di- methacrylate based resins reinforced with submicron glass filler particles. The Brazilian disk test was used on precracked chevron-notched specimens, and different stress states were obtained by angulating the precracked chevron notch relative to the diametral compressive loading direction. The stress intensity factors were calculated using Atkinson et al.'s relation. For all three materials, mode I fracture toughness values ranged between 0.48-0.64 MPa. m(0.5) and mode II values ranged between 0.93-1.2 MPa. m(0.5). Overall, aging time and storage media had little effect on toughness. Considering the inherently low toughness of these restorative materials, their use should be limited to low stress masticatory areas.}, } @article {pmid10883050, year = {2000}, author = {Reichenheim, ME and Best, NG}, title = {A Bayesian approach to estimate the prevalence of low height-for-age from the prevalence of low weight-for-age.}, journal = {Cadernos de saude publica}, volume = {16}, number = {2}, pages = {517-531}, doi = {10.1590/s0102-311x2000000200022}, pmid = {10883050}, issn = {0102-311X}, mesh = {Age Factors ; *Bayes Theorem ; *Body Height ; *Body Weight ; Brazil/epidemiology ; Child ; Growth Disorders/*epidemiology ; Humans ; Markov Chains ; Prevalence ; }, abstract = {Victora et al. (1998) proposed the use of low weight-for-age prevalence to estimate the prevalence of height-for-age deficit in Brazilian children. This procedure was justified by the need to simplify methods used in the context of community health programs. From the same perspective, the present article broadens this proposal by using a Bayesian approach (based on Markov Chain Monte Carlo (MCMC) methods) to deal with the imprecision resulting from Victora et al.'s model. In order to avoid invalid estimated prevalence values which can occur with the original linear model, truncation or a logit transformation of the prevalences are suggested. The Bayesian approach is illustrated using a community study as an example. Imprecision arising from methodological complexities in the community study design, such as multi-stage sampling and clustering, is easily handled within the Bayesian framework by introducing a hierarchical or multilevel model structure. Since growth deficit was also evaluated in the community study, the article may also serve to validate the procedure proposed by Victora et al.}, } @article {pmid10865740, year = {2000}, author = {Mazariegos, M and Klassen, P and Solomons, NW and Fürst, P}, title = {Bioelectrical impedance spectroscopy in health and disease. Correspondence between whole body and segmental bioelectrical impedance spectroscopy indices in patients with classical dengue fever.}, journal = {Annals of the New York Academy of Sciences}, volume = {904}, number = {}, pages = {205-209}, doi = {10.1111/j.1749-6632.2000.tb06451.x}, pmid = {10865740}, issn = {0077-8923}, mesh = {Adult ; *Body Composition ; Dengue/*physiopathology ; *Electric Impedance ; Follow-Up Studies ; Guatemala ; Humans ; Reference Values ; Time Factors ; }, abstract = {Bioelectrical impedance spectroscopy (BIS) can provide estimates of body composition for both whole body (WB) and body segments (BS). In normal, healthy subjects, BS measurements may be expected to serve as surrogates for WB indices; however, very little is known about this correspondence in people suffering from acute illnesses. The aim of this study was to evaluate the degree of this correspondence in patients with an acute, systemic illness, such as classical dengue fever. Ten adult patients were examined upon admission to the community hospital on the Pacific Coast of Guatemala and after clinical recovery about two weeks later, and compared with a group of healthy subjects living in the same region. BIS was measured with a Xitron 4000B analyzer (Xitron Technologies Inc., San Diego, CA, USA). BS measurements were carried out using Organ et al.'s approach. The BIS data were modeled with the manufacturer's software: extra- (Recf) and intracellular- (Ricf) resistances, and the Recf/Ricf ratio. BIS BS measurements correlate closely with WB in both the acute and the recovery stages of dengue fever, with the leg showing the highest degree of correspondence and the trunk the lowest. Recf indices, per se, generally showed higher correspondence than Ricf or the Recf/Ricf ratio.}, } @article {pmid10857660, year = {2000}, author = {Billingsley, R and Smith, ML}, title = {Intelligence profiles in children and adolescents with left temporal lobe epilepsy: relationship to language laterality.}, journal = {Brain and cognition}, volume = {43}, number = {1-3}, pages = {44-49}, pmid = {10857660}, issn = {0278-2626}, mesh = {Adolescent ; Child ; Child, Preschool ; Epilepsy, Temporal Lobe/*complications ; Female ; Functional Laterality/physiology ; Humans ; *Intelligence ; Language Disorders/diagnosis/*etiology ; Male ; Severity of Illness Index ; Wechsler Scales ; }, abstract = {Pre- and postoperative IQ profiles were examined in children and adolescents with left temporal-lobe epilepsy. Participants were grouped according to their pattern of speech dominance, as indicated by the intracarotid sodium amobarbital procedure. Seven participants with typical (left hemisphere) speech representation were matched for age and sex to seven participants with atypical (bilateral or right hemisphere) speech representation. The group with atypical speech representation tended to perform worse pre- and postoperatively on several verbal and nonverbal subtests. Unlike Strauss et al.'s (1990) sample, however, the groups did not differ significantly on pre- or postoperative Performance IQ. The results suggest that when individuals are matched closely for age and sex, there may only be limited support for a nonverbal "crowding" hypothesis. Atypical speech representation in children and adolescents with early temporal-lobe epilepsy appears to be associated with lowered performance on both verbal and nonverbal IQ subtests.}, } @article {pmid10832515, year = {2000}, author = {Williamson, J and Ranyard, R and Cuthbert, L}, title = {A conversation-based process tracing method for use with naturalistic decisions: an evaluation study.}, journal = {British journal of psychology (London, England : 1953)}, volume = {91 (Pt 2)}, number = {}, pages = {203-221}, doi = {10.1348/000712600161790}, pmid = {10832515}, issn = {0007-1269}, mesh = {Adult ; Aged ; Analysis of Variance ; *Choice Behavior ; *Decision Making ; Factor Analysis, Statistical ; Female ; Humans ; Male ; Middle Aged ; Statistics, Nonparametric ; *Thinking ; *Verbal Behavior ; }, abstract = {This study is an evaluation of a process tracing method developed for naturalistic decisions, in this case a consumer choice task. The method is based on Huber et al.'s (1997) Active Information Search (AIS) technique, but develops it by providing spoken rather than written answers to respondents' questions, and by including think aloud instructions. The technique is used within a conversation-based situation, rather than the respondent thinking aloud 'into an empty space', as is conventionally the case in think aloud techniques. The method results in a concurrent verbal protocol as respondents make their decisions, and a retrospective report in the form of a post-decision summary. The method was found to be virtually non-reactive in relation to think aloud, although the variable of Preliminary Attribute Elicitation showed some evidence of reactivity. This was a methodological evaluation, and as such the data reported are essentially descriptive. Nevertheless, the data obtained indicate that the method is capable of producing information about decision processes which could have theoretical importance in terms of evaluating models of decision-making.}, } @article {pmid10829727, year = {2000}, author = {Dan, M and Cheeke, JD and Kondic, L}, title = {Dependence of single-bubble sonoluminescence on ambient pressure.}, journal = {Ultrasonics}, volume = {38}, number = {1-8}, pages = {566-569}, doi = {10.1016/s0041-624x(99)00196-1}, pmid = {10829727}, issn = {1874-9968}, abstract = {Kondic et al.'s theory makes several specific predictions on the dependence of single-bubble sonoluminescence (SBSL) on ambient pressure. We have carried out experiments to verify these predictions for air bubbles in a water-glycerine mixture at about 17.5 kHz. The results show an increase in SBSL with reduced ambient pressure down to a critical value below which SBSL is extinguished. The results are all in good agreement with Kondic et al.'s theory and are also compatible with the dissociation hypothesis of Lohse et al.}, } @article {pmid10828556, year = {2000}, author = {Kanazawa, S and Still, MC}, title = {Teaching may be hazardous to your marriage.}, journal = {Evolution and human behavior : official journal of the Human Behavior and Evolution Society}, volume = {21}, number = {3}, pages = {185-190}, doi = {10.1016/s1090-5138(00)00026-x}, pmid = {10828556}, issn = {1090-5138}, abstract = {Kenrick et al.'s experiments demonstrate that men who view photographs of physically attractive women or Playboy centerfolds subsequently find their current mates less physically attractive and become less satisfied with their current relationships. What then would be the cumulative effect of being exposed to young, attractive women on a daily basis? Would there be any real consequences to the men's dissatisfaction with their relationships? Secondary school teachers and college professors come in contact with more young women at the peak of their reproductive value than others do. The analysis of a large, representative data set from the United States indicates that, while men in general are less likely to be divorced than women, and secondary school teachers and college professors in general are less likely to be divorced than others, simultaneously being male and being a secondary school teacher or college professor statistically increases the likelihood of being divorced (p <.05). We contend that the contrast effect that Kenrick et al. find in their experiments is cumulative and has real consequences.}, } @article {pmid10822506, year = {1999}, author = {Kawasaki, M and Ishizaki, H and Matsumoto, T and Matsuda, T and Nishimura, K and Miyaji, M}, title = {Mitochondrial DNA analysis of Exophiala jeanselmei var. lecanii-corni and Exophiala castellanii.}, journal = {Mycopathologia}, volume = {146}, number = {2}, pages = {75-77}, pmid = {10822506}, issn = {0301-486X}, mesh = {DNA, Fungal/analysis ; DNA, Mitochondrial/*analysis ; Exophiala/*classification/*genetics/isolation & purification ; Humans ; Mycoses/microbiology ; Polymorphism, Restriction Fragment Length ; }, abstract = {A Japanese clinical isolate (KU-A-0094) which was identified by de Hoog et al. as Exophiala jeanselmei var. lecanii-corni with difficulty, was compared with 5 strains including the type cultures of E. jeanselmei var. lecanii-corni, var. jeanselmei and E. castellanii using RFLP (restriction fragment length polymorphism) patterns of mtDNA (mitochondrial DNA). RFLP patterns of KUA-0094 were identical with those of E. jeanselmei var. lecanii-corni and different from those of E. castellanii with restriction enzymes of HaeIII, MspI and hindIII. Therefore, de Hoog et al.'s identification of KU-A-0094 was confirmed. Additionally, mtDNA-RFLP patterns of E. jeanselmei var. lecanii-corni and E. jeanselmei var. jeanselmei were also different from each other. Consequently E. jeanselmei var. lecanii-corni seem to be a species in its own right rather than a variant of E. jeanselmei.}, } @article {pmid10781701, year = {2000}, author = {Moerk, KC and Klein, DN}, title = {The development of major depressive episodes during the course of dysthymic and episodic major depressive disorders: a retrospective examination of life events.}, journal = {Journal of affective disorders}, volume = {58}, number = {2}, pages = {117-123}, doi = {10.1016/s0165-0327(99)00102-0}, pmid = {10781701}, issn = {0165-0327}, mesh = {Adult ; Depressive Disorder, Major/*diagnosis/psychology ; Dysthymic Disorder/*diagnosis/psychology ; Female ; Humans ; *Life Change Events ; Longitudinal Studies ; Male ; Personality ; Personality Assessment ; Retrospective Studies ; Risk Factors ; }, abstract = {BACKGROUND: The present study examined whether stressful life events are associated with the development of major depressive episodes (MDEs) in a longitudinal, retrospective study of dysthymic and episodic major depressive disorders.

METHODS: Sixty-seven outpatients with DSM-III-R dysthymia and 38 outpatients with non-chronic major depression were followed up 30-60 months after entry into the study. Follow-up assessments included a modified version of Paykel's (1997) Interview for Recent Life Events (IRLE) and Keller et al.'s (1987) Longitudinal Interval Follow-up Evaluation. Life events were assessed retrospectively in the 6 months before the most recent MDE or in the 6 months before follow-up for patients without a MDE.

RESULTS: In dysthymic patients, MDEs were significantly associated with a new life event in the context of an ongoing chronic stressor. In episodic major depressive patients, relapses were associated with new life events regardless of an ongoing chronic stressor.

LIMITATIONS: This was a retrospective study. It was also a conservative test of the association between life events and MDEs as the follow-up period over which life events were assessed was long, increasing the possibility of forgetting; events occurring less than 1 month before relapse were excluded to avoid confounding the event with the MDE; life events were assessed for a more distant time period for patients who experienced MDEs than those who did not; and an abbreviated version of the IRLE was used which may have failed to identify less severe events.

CONCLUSIONS: This study suggests that life events may play a role in the onset of MDEs in persons with dysthymic disorder and those with major depressive disorder. Thus, clinicians should monitor dysthymic patients after a stressful life event, particularly if it occurs in the context of a chronic, ongoing stressor.}, } @article {pmid10775705, year = {2000}, author = {Caramazza, A}, title = {Minding the facts: a comment on Thompson-Schill et al.'s "A neural basis for category and modality specificity of semantic knowledge".}, journal = {Neuropsychologia}, volume = {38}, number = {7}, pages = {944-949}, doi = {10.1016/s0028-3932(00)00022-1}, pmid = {10775705}, issn = {0028-3932}, support = {NS22201/NS/NINDS NIH HHS/United States ; }, mesh = {Auditory Perception/physiology ; Brain/physiology ; Humans ; *Knowledge ; Magnetic Resonance Imaging ; Semantics ; Visual Perception/physiology ; }, abstract = {In this comment on a recent paper by Thompson-Schill et al. (1999) I argue that the authors failed to consider important empirical facts that are at variance with their favored theory of the causes of semantic category-specific deficits. I also argue that the predictions they make about fusiform gyrus activation on the basis of the interactive modality-specific hypothesis of semantic organization do not obviously follow from that model. I point out that simulations are needed in order to derive predictions from the model. Finally, I argue that the fMRI results they obtained are not obviously relevant to our understanding of the causes of semantic category-specific deficits.}, } @article {pmid10764105, year = {2000}, author = {Klinger, MR and Burton, PC and Pitts, GS}, title = {Mechanisms of unconscious priming: I. Response competition, not spreading activation.}, journal = {Journal of experimental psychology. Learning, memory, and cognition}, volume = {26}, number = {2}, pages = {441-455}, doi = {10.1037//0278-7393.26.2.441}, pmid = {10764105}, issn = {0278-7393}, mesh = {Adult ; *Attention ; Female ; Humans ; Male ; *Mental Recall ; *Paired-Associate Learning ; Semantics ; }, abstract = {Four experiments were conducted to replicate and expand upon A. G. Greenwald, S. C. Draine, and R. L. Abrams's (1996) demonstration that unconsciously perceived priming words can influence judgments of other words. The present experiments manipulated 2 types of relationships between priming and target stimuli: (a) whether priming and target stimuli possess a preexisting semantic relationship (an affective relationship in Experiments 1, 2, and 4; an associative relationship in Experiment 3; and an animacy relationship in Experiment 4) and (b) whether the primes and targets produce the same response. Large priming effects were found only when the primes and targets possessed response compatibility. No residual effects for affective, animacy, or semantic relatedness were observed. Although these results strongly support the conclusion that word meaning can be unconsciously activated, they do not support the claim that the unconscious perception effects obtained in Greenwald et al.'s (1996) paradigm are caused by automatic spreading activation of word meaning. Instead, the results reported here are consistent with a claim that unconsciously perceived words automatically trigger response tendencies that facilitate or interfere with target responding.}, } @article {pmid10740972, year = {2000}, author = {Maratsos, M}, title = {More overregularizations after all: new data and discussion on Marcus, Pinker, Ullman, Hollander, Rosen & Xu.}, journal = {Journal of child language}, volume = {27}, number = {1}, pages = {183-212}, doi = {10.1017/s0305000999004067}, pmid = {10740972}, issn = {0305-0009}, mesh = {Child ; *Child Language ; Child, Preschool ; Humans ; *Linguistics ; Longitudinal Studies ; }, abstract = {Marcus, Pinker, Ullman, Hollander, Rosen & Xu (1992) claim that when the irregular past form of a verb is known, it is immediately known to be the correct form, such that over-regularizations only occur as speech errors, not as a genuine grammatical alternative; as a result, they argue, over-regularization rates are, when carefully inspected, very low. In the present paper: (1) it is shown that even if over-regularizations are a genuine grammatical alternative, overall rates in samples would still be low for most children; (2) careful analysis shows evidence for substantial over-regularization periods in three longitudinal subjects ages 2;5-5;2 (Abe), 2;3-5;2 (Adam) and 2;3-5;0 (Sarah); (3) Abe's much higher rates follow from general developments in his past tense acquisition, in ways not consonant with Marcus et al.'s formulations.}, } @article {pmid10731766, year = {2000}, author = {Jaśkowski, P and Verleger, R}, title = {An evaluation of methods for single-trial estimation of P3 latency.}, journal = {Psychophysiology}, volume = {37}, number = {2}, pages = {153-162}, pmid = {10731766}, issn = {0048-5772}, mesh = {Algorithms ; Computer Simulation ; Data Interpretation, Statistical ; *Electroencephalography ; Evoked Potentials/*physiology ; Humans ; Research Design ; }, abstract = {This study investigated the validity of procedures for estimating the P3 complex in single trials. In "pseudo-real" simulations of the N1-P2 complex of the occipital visual-evoked potential, Möcks, Köhler, Gasser, and Pham (1988) had reported that their maximum-likelihood method (Pham, Möcks, Köhler, & Gasser, 1987) performed better than Woody's (1967) method. Using pseudo-real simulations of auditory oddball data, we wanted to know whether this finding also held true for the P3 complex. The performance of three methods was studied: peak picking, Woody's method, and Pham et al.'s method (as well as an extension of this latter method). Performance of all methods critically depended on the signal-to-noise ratio. There was some advantage for the more sophisticated methods, particularly when signal-to-noise ratios were realistic. "Good" trials may be selected by all methods, to improve the signal-to-noise ratio, but this selection entails the risk of bias. Further research should investigate whether these conclusions also hold true when the P3 complex consists of more than one component.}, } @article {pmid10696628, year = {2000}, author = {Saiki, J}, title = {Occlusion, symmetry, and object-based attention: comment on Behrmann, Zemel, and Mozer (1998).}, journal = {Journal of experimental psychology. Human perception and performance}, volume = {26}, number = {1}, pages = {424-433}, doi = {10.1037//0096-1523.26.1.424}, pmid = {10696628}, issn = {0096-1523}, mesh = {Adult ; *Attention ; Confounding Factors, Epidemiologic ; Female ; Form Perception ; Humans ; Male ; Models, Psychological ; *Pattern Recognition, Visual ; *Psychomotor Performance ; Reaction Time ; Time Factors ; }, abstract = {The validity of M. Behrmann, R. Zemel, and M. Mozer's (1998) finding that object-based attention can be directed toward occluded objects is examined in 3 experiments. In M. Behrmann et al.'s (1998) original study, participants made speeded judgments of whether the numbers of bumps attached to 2 arms of an X shape were the same or different. The 2 sets of bumps belonged either to a single object, 2 different objects, or 2 separated parts of an occluded object. Unfortunately, this objecthood manipulation was confounded by the symmetry of the stimuli. Experiment 1 replicated M. Behrmann et al.'s main results using identical stimuli. Experiments 2a and 2b dissociated objecthood from symmetry. The results suggest that the effects of object-based attention found by M. Behrmann et al. are largely due to symmetry. The stimuli used in M. Behrmann et al. are not appropriate for examining the relation between object-based attention and occlusion.}, } @article {pmid10693482, year = {1999}, author = {Spencer, N and Newell, R}, title = {The use of brief written educational material to promote reflection amongst trained nurses: a pilot study.}, journal = {Nurse education today}, volume = {19}, number = {5}, pages = {347-356}, doi = {10.1054/nedt.1999.0373}, pmid = {10693482}, issn = {0260-6917}, mesh = {Adult ; Education, Nursing, Continuing/*methods ; Humans ; Middle Aged ; Models, Educational ; Nursing Education Research ; *Nursing Process ; Nursing Staff, Hospital/*education/*psychology ; Pilot Projects ; *Teaching Materials ; *Thinking ; Writing ; }, abstract = {The UKCC (1995) suggest that in order for nurses to maintain their registration, they must maintain a personal professional profile via reflection, and there are numerous approaches to the teaching of reflection. Similarly, several models of reflection exist. However, much of this activity has occurred without attempts to establish the effectiveness of either reflection or attempts to teach it. The current study attempted to examine whether written educational material could significantly improve nurses' reflective ability. Nineteen practising nurses were recruited from a variety of sources and offered an educational package, largely based on Boud et al. (1985) model of reflection in learning. In a repeated measures design study, these participants completed a reflective exercise before and after offering of the educational material. Their scripts were rated, using Wong et al.'s (1995) tool, by three raters, two of whom were unaware of whether the scripts were completed before or after offering of the educational material. An initial analysis showed that there were no statistically significant changes in subjects' reflective ability following education. However, removal from the analysis of 6 participants who had a pre-test ability at the highest possible level (and for whom no improvement was, therefore, possible) resulted in a significant improvement in participants' ability from pre- to post-test (z = -2.4450, P = 0.0145). Interrater reliability calculated using Cronbach's Alpha was 0.7210 for pretest reflective accounts and 0.7369 for post-test reflective accounts.}, } @article {pmid10689555, year = {2000}, author = {Pesta, BJ and Sanders, RE}, title = {Aging and negative priming: is ignored information inhibited or remembered?.}, journal = {Experimental aging research}, volume = {26}, number = {1}, pages = {37-56}, doi = {10.1080/036107300243678}, pmid = {10689555}, issn = {0361-073X}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Aging/*psychology ; *Attention ; Humans ; *Mental Recall ; Middle Aged ; }, abstract = {We had younger and older adults complete two tasks that tested the attentional- and memory-based inhibition models of negative priming. One task violated May, Kane, & Hasher (1995, Psychological Bulletin, 118, 35-54) criteria for measuring just attentional inhibition, by including a repeated-target condition. The other task complied with these criteria and included a depth of processing manipulation, where participants selected prime targets based either on their letter-length (nonsemantic processing) or weight (semantic processing). On balance, results supported the memory model, because depth of processing clearly moderated younger adult negative priming, and older adults displayed negative priming only in the task satisfying the attentional-inhibition criteria (i.e., the depth of processing task). We conclude that memory factors moderate negative priming, and that May et al.'s criteria fail to predict when older adults will show the effect.}, } @article {pmid10687745, year = {1999}, author = {Kitamura, T and Kijima, N and Watanabe, K and Takezaki, Y and Tanaka, E}, title = {Precedents of perceived social support: personality and early life experiences.}, journal = {Psychiatry and clinical neurosciences}, volume = {53}, number = {6}, pages = {649-654}, doi = {10.1046/j.1440-1819.1999.00620.x}, pmid = {10687745}, issn = {1323-1316}, mesh = {Adult ; Age Factors ; Female ; Humans ; Interpersonal Relations ; Japan ; *Life Change Events ; Personal Satisfaction ; *Personality ; Personality Tests ; Social Desirability ; *Social Support ; }, abstract = {In order to examine the effects of personality and early life experiences on perceived social support, a total of 97 young Japanese women were investigated. Current interpersonal relationships were measured by an interview modified from Henderson et al.'s Interview Schedule for Social Interaction (ISSI). Personality was measured by Cloninger et al.'s Temperament and Character Inventory. Early life experiences at home and outside of home were also identified in the interview. The number of sources of perceived support was correlated with self-directness, while satisfaction with perceived support was correlated with novelty seeking and with low harm avoidance. No early life experiences--early loss of a parent, perceived parenting, childhood abuse experiences, experiences of being bullied and/or other life events--showed significant correlations with the number or satisfaction of supportive people. The quantity and quality of perception of social support differ in their link to personality, and perceived social support may, to some extent, be explainable in terms of personality.}, } @article {pmid10672489, year = {2000}, author = {Küpper, T and Haisch, M}, title = {Lumbar spine loads during education and training with self-contained breathing apparatus.}, journal = {International archives of occupational and environmental health}, volume = {73}, number = {1}, pages = {35-40}, doi = {10.1007/pl00007935}, pmid = {10672489}, issn = {0340-0131}, mesh = {Biomechanical Phenomena ; Exercise ; *Fires ; Humans ; Lumbosacral Region ; Models, Biological ; Occupations ; Respiration ; *Respiratory Protective Devices ; Spine/*physiology ; }, abstract = {OBJECTIVE: German fire fighters often complain of lumbar back pain after training with a self-contained breathing apparatus while using a device called 'Schlaghammer' (SH). We investigated whether this training produces an excessive load on the lumbar spine.

METHOD: We developed a model to estimate the load on the lumbar spine using a vector model similar to Jäger et al.'s model. The force at the SH's cable was recorded on-line, and the position of each subject was registered with synchronized series of photos. The influence of the different parameters was calculated by varying these data (+/- 10%) and computing the model.

RESULTS: There is no dangerous load for healthy persons using a correct technique. Improper technique, however, caused by exhaustion or ignorance, can result in high peaks of lumbar spine load.

CONCLUSIONS: The lumbar spine loads involved are acceptable if the exercise is performed with a straight back without bending of the lumbar spine and without sudden acceleration. The direction of the pull should be towards the lumbar spine.}, } @article {pmid10636939, year = {2000}, author = {Ito, H and Tsuji, S}, title = {Model dependence in quantification of spike interdependence by joint peri-stimulus time histogram.}, journal = {Neural computation}, volume = {12}, number = {1}, pages = {195-217}, doi = {10.1162/089976600300015952}, pmid = {10636939}, issn = {0899-7667}, mesh = {Brain/physiology ; Computer Simulation ; *Models, Neurological ; *Models, Statistical ; Neurons/*physiology ; Poisson Distribution ; Probability ; Time Factors ; }, abstract = {Multineuronal recordings have enabled us to examine context-dependent changes in the relationship between the activities of multiple cells. The joint peri-stimulus time histogram (JPSTH) is a much-used method for investigating the dynamics of the interdependence of spike events between pairs of cells. Its results are often taken as an estimate of interaction strength between cells, independent of modulations in the cells' firing rates. We evaluate the adequacy of this estimate by examining the mathematical structure of how the JPSTH quantifies an interaction strength after excluding the contribution of firing rates. We introduce a simple probabilistic model of interacting point processes to generate simulated spike data and show that the normalized JPSTH incorrectly infers the temporal structure of variations in the interaction parameter strength. This occurs because, in our model, the correct normalization of firing-rate contributions is different than that used in Aertsen, Gerstein, Habib, and Palm's (1989) effective connectivity model. This demonstrates that firing-rate modulations cannot be corrected for in a model-independent manner, and therefore the effective connectivity does not represent a universal characteristic that is independent of modulation of the firing rates. Aertsen et al.'s (1989) effective connectivity may still be used in the analysis of experimental data, provided we are aware that this is simply one of many ways of describing the structure of interdependence. We also discuss some measure-independent characteristics of the structure of interdependence.}, } @article {pmid10631072, year = {2000}, author = {Ordóñez, LD and Connolly, T}, title = {Regret and Responsibility: A Reply to Zeelenberg et al. (1998).}, journal = {Organizational behavior and human decision processes}, volume = {81}, number = {1}, pages = {132-142}, doi = {10.1006/obhd.1999.2834}, pmid = {10631072}, issn = {0749-5978}, abstract = {M. Zeelenberg, W. W. van Dijk, and A. S. R. Manstead (1998, Organizational Behavior and Human Decision Processes, 74, 254-272) recently reported an altered replication of our earlier study (T. Connolly, L. D. Ordóñez, & R. Coughlan, 1997, Organizational Behavior and Human Decision Processes, 70, 73-85) concerning the effects of decision agency on regret and outcome evaluation. Our earlier study had found no such effect, but Zeelenberg et al. did. In two new experiments, we have largely confirmed Zeelenberg et al.'s result but have shown that, contrary to most theory, regret (a) can appear even in the absence of decision agency, (b) can be unrelated to outcome evaluations, and (c) may be more influenced by the experience of gains or losses from the status quo than by any decisional responsibility for those changes. Copyright 2000 Academic Press.}, } @article {pmid10615729, year = {1999}, author = {}, title = {Comments on Her et al.'s "Privatizing alcohol sales and alcohol consumption evidence and implications".}, journal = {Addiction (Abingdon, England)}, volume = {94}, number = {8}, pages = {1141-1153}, pmid = {10615729}, issn = {0965-2140}, mesh = {Alcohol Drinking/*economics ; Alcohol-Related Disorders/economics ; Alcoholic Beverages/*economics/supply & distribution ; Humans ; *Privatization ; }, } @article {pmid10604086, year = {1999}, author = {McWilliams, LA and Asmundson, GJ}, title = {Alcohol consumption in university women: a second look at the role of anxiety sensitivity.}, journal = {Depression and anxiety}, volume = {10}, number = {3}, pages = {125-128}, pmid = {10604086}, issn = {1091-4269}, mesh = {Adult ; Alcohol Drinking/*psychology ; Analysis of Variance ; Anxiety/*psychology ; Female ; Humans ; Psychiatric Status Rating Scales ; Regression Analysis ; Sampling Studies ; Students/*psychology ; Universities ; }, abstract = {The study reexamined the relationship between anxiety sensitivity (AS) and drinking behavior in a sample of university women (N = 197) taking into account recent theoretical considerations regarding the possible hierarchical nature of the AS construct. To assess the incremental validity of this construct, the amount of variance in drinking behavior accounted for by measures of AS and trait anxiety was investigated with several multiple regression analyses. Contrary to expectations, measures of both constructs failed to account for significant variance in drinking behavior. McNally's [1996: Rapee RM, editor. Current Controversies in anxiety disorders. p 214-244] hypothesis regarding a trait anxiety by AS interaction received weak support as the combination of these two variables accounted for a small (i.e., 1.6%) portion of variance in one drinking variable (viz., monthly intoxication). Correlational analyses revealed only two small and marginally significant associations between the lower-order components of AS (i.e., fears of physical, cognitive, and publicly observable symptoms of anxiety) and the drinking measures. Potential reasons for the failure to replicate or extend Stewart et al.'s [1995: J Anxiety Disord 9:283-392] findings of significant positive associations between AS and both weekly alcohol consumption and excessive drinking are discussed.}, } @article {pmid10553738, year = {1999}, author = {Simpson, GM and Josiassen, RC and Stanilla, JK and de Leon, J and Nair, C and Abraham, G and Odom-White, A and Turner, RM}, title = {Double-blind study of clozapine dose response in chronic schizophrenia.}, journal = {The American journal of psychiatry}, volume = {156}, number = {11}, pages = {1744-1750}, doi = {10.1176/ajp.156.11.1744}, pmid = {10553738}, issn = {0002-953X}, support = {MI-145190//PHS HHS/United States ; }, mesh = {Antipsychotic Agents/administration & dosage/*therapeutic use ; Brief Psychiatric Rating Scale/statistics & numerical data ; Clozapine/administration & dosage/*therapeutic use ; Cross-Sectional Studies ; Dose-Response Relationship, Drug ; Double-Blind Method ; Drug Administration Schedule ; Female ; Haloperidol/administration & dosage/therapeutic use ; Humans ; Male ; Psychotic Disorders/drug therapy/psychology ; Schizophrenia/*drug therapy ; Schizophrenic Psychology ; Treatment Outcome ; }, abstract = {OBJECTIVE: This study explored the relative efficacy of three different doses of clozapine.

METHOD: Fifty patients who met Kane et al.'s criteria for treatment-refractory schizophrenia or schizoaffective disorder were studied. All subjects were randomly assigned to 100, 300, or 600 mg/day of clozapine for 16 weeks of double-blind treatment. Forty-eight patients completed this first 16 weeks. Of the 50 patients, 36 went on to second and third 16-week trials of double-blind treatment at the remaining doses.

RESULTS: Four subjects (8%) responded to the first 16-week condition, and one subject (2%) responded to the next 16-week crossover condition. A chi-square comparison of the response rates from the three dose groups failed to show a significant effect. An analysis of variance (ANOVA) comparison of Brief Psychiatric Rating Scale-Anchored (BPRS-A) total change scores from baseline to last observation carried forward showed a significant dose effect (600>300>100 mg/day) at 16 weeks of treatment. A crossover ANOVA of the BPRS-A total scores from the 48-week study also showed that the main effect for dose was highly significant; the 100-mg/day dose gave the higher (poorer) values, and the 300- and 600-mg/ day doses gave equal (better) values. Gender played a role in clinical response to treatment at 100 mg/day.

CONCLUSIONS: Clozapine treatment at 100 mg/day was less effective than at 300 or 600 mg/day. At 100 mg/day, women responded better than did men. The 600 mg/day group had the best results, but an occasional patient required up to 900 mg/day. Overall response rates were lower than expected.}, } @article {pmid10573893, year = {1999}, author = {Lentz, JJ and Richards, VM and Matiasek, MR}, title = {Different auditory filter bandwidth estimates based on profile analysis, notched noise, and hybrid tasks.}, journal = {The Journal of the Acoustical Society of America}, volume = {106}, number = {5}, pages = {2779-2792}, doi = {10.1121/1.428137}, pmid = {10573893}, issn = {0001-4966}, support = {DC 02012/DC/NIDCD NIH HHS/United States ; }, mesh = {Auditory Perception/*physiology ; Auditory Threshold/*physiology ; Humans ; *Noise ; Perceptual Masking/physiology ; Psychophysics ; }, abstract = {Auditory filter bandwidths were estimated in three experiments. The first experiment was a profile-analysis experiment. The stimuli were composed of sinusoidal components ranging in frequency from 200 to 5000 Hz. The standard stimulus was the sum of equal-amplitude tones, and the signal stimulus had a power spectrum that varied up-down ... up-down. The number of components ranged from four to 60. Interval-by-interval level randomization prevented the change in level of a single component from reliably indicating the change from standard to signal. The second experiment was a notched-noise experiment in which the 1000-Hz tone to be detected was added to a noise with a notch arithmetically centered at 1000 Hz. Detection thresholds were estimated both in the presence of and in the absence of level randomization. In the third, hybrid, experiment a 1000-Hz tone was to be detected, and the masker was composed of equal-amplitude sinusoidal components ranging in frequency from 200 to 5000 Hz. For this experiment, thresholds were estimated both in the presence and absence of level variation. For both the notched-noise and hybrid experiments, only modest effects of level randomization were obtained. A variant of Durlach et al.'s channel model ["Towards a model for discrimination of broadband signals," J. Acoust. Soc. Am. 80, 63-72 (1986)] was used to estimate auditory filter bandwidths for all three experiments. When a two-parameter roex(p,r) filter weighting function was used to fit the data, bandwidth estimates were approximately two to three times as large for the two detection tasks than for the profile-analysis task.}, } @article {pmid10554595, year = {1999}, author = {Ruchkin, DS and Johnson, R and Friedman, D}, title = {Scaling is necessary when making comparisons between shapes of event-related potential topographies: a reply to Haig et al.}, journal = {Psychophysiology}, volume = {36}, number = {6}, pages = {832-834}, pmid = {10554595}, issn = {0048-5772}, support = {NS11199/NS/NINDS NIH HHS/United States ; }, mesh = {*Analysis of Variance ; *Data Interpretation, Statistical ; Electroencephalography ; Evoked Potentials/*physiology ; Humans ; }, abstract = {A. R. Haig, E. Gordon, and S. Hook (1997) disputed G. McCarthy and C. C. Wood's (1985) contention that scaling should be used when assessing the statistical significance of between condition (or group) differences in the shapes of event-related potential (ERP) scalp topographies. Haig et al. based their contention upon the lack of empirical realism in McCarthy and Wood's model of within-group ERP noise, claiming that McCarthy and Wood's results could not be generalized to realistic ERP data. We argue, on both empirical and theoretical grounds, that Haig et al. do not make a compelling case against generalization of McCarthy and Wood's results. Moreover, Haig et al.'s conclusion is based upon a misconception of how scaling should be used. We conclude that when a quantitative measure of differences between topographic shapes is needed, scaling is not an option--it is a requirement.}, } @article {pmid10547672, year = {1999}, author = {Ginsberg, HS}, title = {The life and times of adenoviruses.}, journal = {Advances in virus research}, volume = {54}, number = {}, pages = {1-13}, doi = {10.1016/s0065-3527(08)60363-2}, pmid = {10547672}, issn = {0065-3527}, mesh = {Adenovirus Infections, Human/history/*virology ; Adenoviruses, Human/*isolation & purification/physiology ; Animals ; History, 20th Century ; Humans ; Mice ; Rats ; Respiratory Tract Infections/history/*virology ; United States ; }, abstract = {With Wallace Rowe et al.'s and Hilleman and Werner's isolations of viruses, subsequently termed "adenoviruses," a new area of research opened for me and gradually for many others. I was quickly able to associate the viruses with diseases in humans, and then our attention turned to the structure of the virion and how it replicated. Many virologists entered these areas of adenovirus research, for they were the central themes for most virologists at that time. We obtained more and more knowledge of the structure of the virion, its genome, and how it replicated and killed cells in culture so that they could no longer divide, although the virus infection did not lyse the infected cells, but we did not have the slightest idea how Ad5 produced disease in vivo. Then Wallace Clyde's timely note appeared, and we entered an exciting and profitable new field: an investigation of the mechanism by which Ad5 produces pneumonia. It must again be emphasized that the pneumonia that WtAd5 produces in cotton rats is pathologically very similar to that induced in humans. One of our earliest sets of experiments in the cotton rats was designed to determine whether region E3 was really nonessential even though the genes contained therein were not required for viral replication. We soon demonstrated that deletion of the E3 region produced a mutant that induced a highly pathogenic viral pneumonia. The potential role in pathogenesis of each of the genes within the E3 region was then investigated. Of maximum importance was the finding that deletion of the 19-kDa gene near the 5' end of the region produced a severe inflammatory response. This result led to the discovery that the E3 19-kDa protein regulated expression of the MHC factor on the surface of infected cells, and deletion of this gene produced a marked increase in MHC on the surfaces of infected cells and, therefore, a marked increase in the response of cytotoxic T cells. In addition, deletion of the gene encoding the 14.7-kDa protein, which was situated at the 3' end of the E3 region, resulted in an increase in polymorphonuclear leukocytes in the inflammatory response. A number of these findings led to hypotheses that could not be tested in the cotton rat since the necessary reagents were not available. Fortunately, our findings that only early viral genes are required to produce full pathogenesis led us to test mice because we had shown in a culture of mouse cells that all of the early viral genes are expressed. The C57BL/6N mouse proved to be an excellent host in which Ad5 produced full pulmonary inflammation. Thus, it was possible to test our hypotheses and to demonstrate their validity, showing that the virus induces cytokine elaboration, as well as to demonstrate the role of cytotoxic T cells in permitting Ad5 to produce persistent infections in lymphoid cells of organs such as the adenoid, from which the first adenovirus was isolated, and which had immediately led to my interest in investigating it and helping to develop the story of adenoviruses.}, } @article {pmid10547129, year = {1999}, author = {McKitrick, LA and Friedman, LF and Brooks, JO and Pearman, A and Kraemer, HC and Yesavage, JA}, title = {Predicting response of older adults to mnemonic training: who will benefit?.}, journal = {International psychogeriatrics}, volume = {11}, number = {3}, pages = {289-300}, doi = {10.1017/s1041610299005852}, pmid = {10547129}, issn = {1041-6102}, support = {MH 18905/MH/NIMH NIH HHS/United States ; MH 35182/MH/NIMH NIH HHS/United States ; }, mesh = {Aged ; Aged, 80 and over ; *Association Learning ; Female ; Follow-Up Studies ; Forecasting ; Humans ; *Learning ; Male ; Memory/*physiology ; Middle Aged ; }, abstract = {OBJECTIVES: To identify profiles of subjects who respond to mnemonic training for serial word and proper name recall.

DESIGN: Analysis of J. O. Brooks et al.'s (1999) mnemonic training data using Quality Receiver Operating Characteristic (QROC) and longitudinal regression analyses (LRA).

SETTING: Community.

PARTICIPANTS: 224 community-dwelling adults 55 years of age and older who wished to improve their memory.

MEASUREMENTS: Performance on serial word and proper name tests; performance on cognitive ability tests.

RESULTS: Although the QROC and LRA identified several common predictors (baseline performance, mental rotation ability, and paired associate learning), the QROC identified additional predictors and cognitive ability profiles associated with successful response.

CONCLUSIONS: Similar degrees of response to mnemonic training are associated with heterogeneous cognitive profiles. This finding highlights the fact that participants rely on a variety of abilities to derive benefit from mnemonic training and thus suggests different avenues from which to approach this training.}, } @article {pmid10493652, year = {1999}, author = {Neiderhiser, JM and Bussell, DA and Pike, A and Plomin, R and Simmens, S and Howe, GW and Hetherington, EM and Reiss, D}, title = {The importance of shared environmental influences in explaining the overlap between mother's parenting and sibling relationships: reply to Neale (1999).}, journal = {Developmental psychology}, volume = {35}, number = {5}, pages = {1265-1267}, pmid = {10493652}, issn = {0012-1649}, mesh = {Adolescent ; Adolescent Behavior/*psychology ; *Environment ; Female ; Humans ; Male ; *Mother-Child Relations ; *Parenting ; Psychology, Adolescent ; *Sibling Relations ; }, abstract = {This article addresses concerns raised by M. C. Neale (1999) in his commentary on the D. A. Bussell et al. (1999) Nonshared Environment in Adolescent Development (NEAD) study. These concerns fall into two categories: (a) model assumptions and sample design and (b) testing of alternative models. The validity of the assumptions of quantitative genetic models is a concern for all researchers in this area. Discussion of those assumptions in this reply is brief and focuses on those most relevant to the NEAD sample. The two alternative models proposed by Neale were designed to provide alternatives to the large shared environmental effect found in the original report of Bussell et al. Because these alternative models did not provide a better fit, the appropriateness of Bussell et al.'s basic model and the importance of shared environmental influences for explaining the association among family subsystems are supported.}, } @article {pmid10486332, year = {1999}, author = {Cooper, G and Amos, W and Bellamy, R and Siddiqui, MR and Frodsham, A and Hill, AV and Rubinsztein, DC}, title = {An empirical exploration of the (delta mu)2 genetic distance for 213 human microsatellite markers.}, journal = {American journal of human genetics}, volume = {65}, number = {4}, pages = {1125-1133}, pmid = {10486332}, issn = {0002-9297}, support = {//Wellcome Trust/United Kingdom ; }, mesh = {Africa ; Alleles ; Chromosome Mapping/*methods/statistics & numerical data ; Gene Frequency/genetics ; Genetic Linkage/*genetics ; Genetic Markers/*genetics ; Heterozygote ; Humans ; India ; Italy ; Least-Squares Analysis ; Microsatellite Repeats/*genetics ; Phylogeny ; Sample Size ; Sensitivity and Specificity ; Time Factors ; }, abstract = {Microsatellites are now used ubiquitously as genetic markers. One important application is to the assessment of population subdivision and phylogenetic relatedness. Such applications require a method of estimation of genetic distance. Here we examine the most widely used measure of microsatellite genetic distance, Goldstein et al.'s delta-mu squared ([delta mu]2), with respect to a large data set of 213 markers typed across samples from four diverse human populations. We find that (delta mu)2 yields plausible interpopulation distances. For the first time, we report significant interpopulation differences in mean microsatellite length, although the effect of these differences on (delta mu)2 is negligible. However, we also show that the method is extremely sensitive to one or two loci that contribute extreme values, even when a sample size of >200 loci is used. Some of these extreme loci can be removed on the grounds that some alleles carry large indels, but for others there is no clear justification for exclusion a priori. Our data suggest a rather recent African/non-African split, with an upper limit of some 70,000-80,000 years ago.}, } @article {pmid10483654, year = {1999}, author = {Holmes, GR and Thornhill, JT}, title = {Part 1 behavioral science scores: after a summer psychiatric research clerkship: failure to replicate.}, journal = {Perceptual and motor skills}, volume = {88}, number = {2}, pages = {622-624}, doi = {10.2466/pms.1999.88.2.622}, pmid = {10483654}, issn = {0031-5125}, mesh = {Achievement ; Behavioral Sciences/*education ; *Clinical Clerkship ; Clinical Competence ; Educational Measurement/*statistics & numerical data ; Female ; Humans ; Male ; Psychiatry/*education ; Students, Medical/*statistics & numerical data ; }, abstract = {The present study did not replicate Holmes,' et al.'s (1987) findings that medical students who participated in a summer psychiatric research clerkship scored statistically significantly higher than matched controls on the Behavioral Science portion of the National Board of Medical Examiners' Part I Exam. Group ns in this replication were 39 each.}, } @article {pmid10477943, year = {1999}, author = {McLeod, JS and Boyer, KM and Ouchi, BY and Cole, JC and Callaghan, RL}, title = {Exploring effects of different pictorial stimuli on written expression.}, journal = {Psychological reports}, volume = {84}, number = {3 Pt 2}, pages = {1225-1234}, doi = {10.2466/pr0.1999.84.3c.1225}, pmid = {10477943}, issn = {0033-2941}, mesh = {Adolescent ; Adult ; Creativity ; Female ; Humans ; Male ; Middle Aged ; Motivation ; *Pattern Recognition, Visual ; *Writing ; }, abstract = {This study explored how the type of pictorial stimulus affects the quality of an individual's written expression. Cole, Muenz, Ouchi, Kaufman, and Kaufman in 1997 furnished initial evidence supporting Hooper, et al.'s 1994 theory. A pictorial stimulus different from that used by Cole, et al. was developed from Hooper, et al.'s specifications, i.e., pictorial stimuli should be photographs rather than line drawings, should have a clear protagonist and should present a novel problem-situation that can be solved in a stepwise manner and compared to a conventional line drawing stimulus (from PIAT-R Written Expression) in its ability to evoke writing samples. It was hypothesized that the "Hooper" stimulus would yield higher scores than an atheoretical stimulus on items assessing structure and cohesiveness of the story, but not on items that assess writing mechanics. Participants comprised 25 men and women aged 17 to 46 years. Results indicate that Hooper, et al.'s theory is more plausible than a conventional line-drawing stimulus.}, } @article {pmid10463457, year = {1999}, author = {Matsumoto, H and Takei, N and Saito, H and Kachi, K and Mori, N}, title = {Childhood-onset schizophrenia and obstetric complications: a case--control study.}, journal = {Schizophrenia research}, volume = {38}, number = {2-3}, pages = {93-99}, doi = {10.1016/s0920-9964(99)00010-9}, pmid = {10463457}, issn = {0920-9964}, mesh = {Adolescent ; Asphyxia Neonatorum/complications/epidemiology ; Case-Control Studies ; Child ; Female ; Humans ; Infant, Newborn ; Japan/epidemiology ; Male ; Pregnancy ; *Pregnancy Complications/epidemiology ; Risk Factors ; Schizophrenia, Childhood/epidemiology/*etiology ; Statistics as Topic ; }, abstract = {Obstetric complications (OCs) may be a risk factor for developing schizophrenia. In a recent study of a meta-analysis, the odds ratio for the development of the disorder in adulthood associated with OCs has been reported to be about 2.0 (i.e., a two-fold increase in risk). However, little attention has been paid to the involvement of OCs in risk of the development of childhood-onset schizophrenia. Therefore, the authors examined the relationship between OCs and childhood-onset schizophrenia. Thirty-three children, aged 8-13 years (average 12.4 years), meeting the DSM-III-R criteria for schizophrenia, were compared with controls (children with anxiety disorder) matched for sex and age. Childhood-onset schizophrenics showed significantly greater scores in all of the three measures of OCs according to Parnas et al.'s scale compared with controls. Moreover, those individuals exposed to OCs were 3.5 times as likely to develop schizophrenia as were those without OCs. The risk association between OCs and the disorder was far greater for male than for female schizophrenics. Our results, together with those in previous studies showing the association between OCs and adult-onset schizophrenia, suggest that childhood- and adult-onset schizophrenia may, at least in part, share a common neuropathogenesis.}, } @article {pmid10455625, year = {1999}, author = {McKenna, H}, title = {The role of reflection in the development of practice theory: a case study.}, journal = {Journal of psychiatric and mental health nursing}, volume = {6}, number = {2}, pages = {147-151}, doi = {10.1046/j.1365-2850.1999.620147.x}, pmid = {10455625}, issn = {1351-0126}, mesh = {Attitude of Health Personnel ; Health Facility Closure ; Hospitals, Psychiatric ; Humans ; Mental Disorders/*nursing/*psychology ; Nursing Faculty Practice ; Nursing Methodology Research/*methods ; *Nursing Process ; Nursing Staff, Hospital/*psychology ; *Nursing Theory ; *Power, Psychological ; *Psychiatric Nursing/methods ; Research Design ; *Thinking ; }, abstract = {Many authors view practice theory as the strongest form of theory for an applied discipline like nursing. It is based upon the idea that theory emanates from practice, is strengthened and is returned to inform practice. The first part of this paper is concerned with identifying the contribution that practice theory can make to patient care. While there are many positivistic ways of generating practice theory, one method which is getting increasing attention is reflection. In this paper, Boud et al.'s framework for reflection is used to identify phenomena related to the empowerment of patients and staff in psychiatric hospitals (Boud et al. 1985). A real life case study is described and concepts and beginning propositions are uncovered. Conclusions are drawn which from the basis for theory development and testing.}, } @article {pmid10450465, year = {1999}, author = {Mudford, OC and Hogg, J and Roberts, J}, title = {Behavior states: now you see them, now you don't.}, journal = {American journal of mental retardation : AJMR}, volume = {104}, number = {4}, pages = {385-391}, doi = {10.1352/0895-8017(1999)104<0385:BSNYST>2.0.CO;2}, pmid = {10450465}, issn = {0895-8017}, mesh = {Humans ; Mental Disorders/*diagnosis/epidemiology/*psychology ; Observer Variation ; Reproducibility of Results ; Video Recording ; }, abstract = {Guess, Roberts, Behrens, and Rues (1998) presented reliability data from recordings of behavior state using a 13-category coding system. Interobserver agreement was reported at 63% to 91% across categories. In an attempt at replication, we found lower levels of reliability (0% to 80%). To determine the reasons for different results, we obtained measurements of behavior states from video-recordings by five of Guess et al.'s observers. Again, replication was unsuccessful. Obtained mean percentage agreement on occurrence for individual behavior states and participants ranged across observer pairs from 0% to 58% (kappa range was 0 to .64). Some possible reasons for failures to replicate are discussed.}, } @article {pmid10378171, year = {1999}, author = {Hickling, EJ and Blanchard, EB and Buckley, TC and Taylor, AE}, title = {Effects of attribution of responsibility for motor vehicle accidents on severity of PTSD symptoms, ways of coping, and recovery over six months.}, journal = {Journal of traumatic stress}, volume = {12}, number = {2}, pages = {345-353}, doi = {10.1023/A:1024784711484}, pmid = {10378171}, issn = {0894-9867}, support = {MH-48476/MH/NIMH NIH HHS/United States ; }, mesh = {*Accidents, Traffic ; *Adaptation, Psychological ; Adult ; *Attitude ; *Convalescence ; Female ; Follow-Up Studies ; Humans ; Male ; *Motor Vehicles ; Prospective Studies ; Severity of Illness Index ; Stress Disorders, Post-Traumatic/*diagnosis/*psychology ; }, abstract = {In light of Delahanty et al.'s (1997) identification of attribution of responsibility for a motor vehicle accident (MVA) as a powerful determinant of initial level of distress from the trauma and of early remission of PTSD, we reexamined data from Blanchard and Hickling's (1997) prospective follow-up of 158 MVA survivors. Despite differences between the two samples (Delahanty sample recruited from hospitals 2-3 weeks post-MVA and predominantly male; our sample recruited from outpatient care 1-4 months post-MVA and predominantly female) we replicated Delahanty's findings: those with PTSD who blame themselves for the MVA are less symptomatic initially and recover more rapidly in the first 6 months than those with PTSD who blame another party for the accident.}, } @article {pmid10373317, year = {1999}, author = {Wigfield, A and Byrnes, JP}, title = {Does Math-Fact Retrieval Explain Sex Differences in Mathematical Test Performance? A Commentary.}, journal = {Contemporary educational psychology}, volume = {24}, number = {3}, pages = {275-285}, doi = {10.1006/ceps.1999.1008}, pmid = {10373317}, issn = {0361-476X}, abstract = {We focus on four issues in commenting on Royer et al.'s work testing their hypothesis that sex differences in test performance can be explained by differences in math-fact retrieval latency. The first issue is whether the studies conducted by Royer et al. directly test their hypothesis; we argue that they do not. The second issue involves questions about the strength of the gender differences in math-fact retrieval. The third is whether math-fact retrieval should be considered the major mechanism in explaining the differences in test performance. In considering this third issue we discuss other theories regarding the nature of math problem solving that are useful for understanding test performance differences between males and females. The fourth issue is what particular experiential differences boys and girls have in math classrooms could contribute to the sex differences in test performance. We also consider sex differences in math attitudes and motivation. Copyright 1999 Academic Press.}, } @article {pmid10371875, year = {1999}, author = {Brennen, T}, title = {Face naming in dementia: a reply to Hodges and Greene (1998).}, journal = {The Quarterly journal of experimental psychology. A, Human experimental psychology}, volume = {52}, number = {2}, pages = {535-541}, doi = {10.1080/713755816}, pmid = {10371875}, issn = {0272-4987}, mesh = {Anomia/*physiopathology ; *Association ; Dementia/*physiopathology ; *Face ; Humans ; Memory/*physiology ; Names ; Pattern Recognition, Visual/physiology ; *Semantics ; }, abstract = {A case study by Brennen, David, Fluchaire, and Pellat (1996) reported the case of a patient who could occasionally name celebrities with very low concurrent levels of semantic access, which is difficult to reconcile with current models of face identification. Hodges and Greene (1998) attribute Brennen et al.'s case study to artifactual explanations and provide new data, which, they claim, is evidence against the "theory of naming without semantics". This reply demonstrates that Hodges and Greene's arguments are unconvincing and that aspects of Hodges and Greene's data in fact provide support for Brennen et al.'s conclusions. It is also argued that in cases of dementia direct naming has been reported for other stimuli domains as well.}, } @article {pmid10343179, year = {1999}, author = {Lutz-Bucher, B and González de Aguilar, JL and René, F and Sée, V and Gordon, JW and Loeffler, J}, title = {Oxidative stress and a murine superoxide dismutase-1 mutation promoting amyotrophic lateral sclerosis alter neurosecretion in the hypothalamo-neurohypophyseal axis.}, journal = {Neuroendocrinology}, volume = {69}, number = {5}, pages = {377-384}, doi = {10.1159/000054440}, pmid = {10343179}, issn = {0028-3835}, support = {AG10520/AG/NIA NIH HHS/United States ; }, mesh = {Amyotrophic Lateral Sclerosis/enzymology/*genetics ; Animals ; Blotting, Western ; Cyclic AMP/metabolism ; Cyclic GMP/biosynthesis ; Female ; Hydrogen Peroxide/pharmacology ; Hypothalamo-Hypophyseal System/drug effects/*metabolism ; Hypothalamus/drug effects/metabolism ; Lipid Peroxidation/drug effects/genetics ; Mice ; Mice, Transgenic ; Mutation/*physiology ; Neuropeptides/pharmacology ; Neurosecretory Systems/drug effects/*metabolism ; Nitric Oxide Synthase/biosynthesis ; Nitric Oxide Synthase Type I ; Oxidants/pharmacology ; Oxidative Stress/*physiology ; Pituitary Adenylate Cyclase-Activating Polypeptide ; Pituitary Gland/drug effects/metabolism ; Superoxide Dismutase/*genetics/pharmacology ; }, abstract = {In this study, we examined the effects of oxidative stress on a nitric oxide (NO)-regulated neuroendocrine function, the release of arginine vasopressin (AVP) by the hypothalamo-neurohypophyseal axis. Treatment of mouse-isolated hypothalami and neurointermediate lobes (NIL) with H2O2 increased AVP release. This effect was inhibited by copper-zinc superoxide dismutase-1 (SOD1) analogs. By measuring cGMP accumulation as an indicator of biologically active NO, we found that H2O2 treatment decreased cGMP formation in both hypothalami and NIL. We have previously shown that NO inhibits AVP release by a cGMP-independent mechanism. Given that H2O2 stimulated AVP release, while it reduced cGMP production, our findings strongly suggest that oxidative damage affects neurosecretion by reducing NO availability. To test whether such a mechanism may operate under pathological conditions with pronounced oxidative stress, we compared neurosecretion in wild-type and transgenic mice carrying a mutated form of SOD1 associated with human familial amyotrophic lateral sclerosis. Reminiscent of the data obtained from H2O2-treated tissues, hypothalami and NIL from SOD1 mutants displayed decreased cGMP accumulation and increased AVP release, compared with tissues from wild-type littermates. Since neuronal NO synthase expression was not modified, we conclude that the perturbed free radical metabolism associated with the SOD1 mutation is likely to trap NO, and thereby alter neurosecretion, a mechanism that can be exacerbated in specific physiopathological conditions.}, } @article {pmid10328897, year = {1999}, author = {Lee, LH}, title = {Relevance of Film Pressures to Interfacial Tension, Miscibility of Liquids, and Lewis Acid-Base Approach.}, journal = {Journal of colloid and interface science}, volume = {214}, number = {1}, pages = {64-78}, doi = {10.1006/jcis.1999.6165}, pmid = {10328897}, issn = {1095-7103}, abstract = {In this paper, we demonstrate the spreading pressure and interfacial film pressure to be profoundly relevant to interfacial tension, miscibility of liquids, and the Lewis acid-base approach. For immiscible liquid-solid and liquid-liquid systems, we prefer to employ Harkins' spreading model containing the equilibrium spreading pressure pie. With the inclusion of pie, we can also improve the Lewis acid-base approach for hydrogen-bonding, proposed by van Oss, Chaudhury, and Good. We establish an acidity-basicity scale for the initial surface tension by taking pie into account, and we further calculate interfacial tensions for liquid pairs containing formamide or dimethyl sulfoxide (DMSO) with dispersion components cited in Fowkes et al.'s later publication. However, for initially immiscible liquid-liquid systems, the Harkins model does not apply, and we propose, instead, an adsorption model, which requires the interfacial tension to be varying and surface tensions of the bulk liquids at a distance from the interface to remain unchanged. Thus, the difference between the initial and equilibrium interfacial spreading coefficients (Si) equals the equilibrium interfacial film pressure (pii)e, and that difference also equals that of the two interfacial tensions. For liquid-liquid systems, we can choose either of these two models depending on the miscibility of liquids. According to our adsorption model, there should be two interfacial tensions. The initial (or calculated) interfacial tension can be positive or negative, while the equilibrium (experimental) interfacial tension can reach zero. The former has more predictive value than the latter. A negative, initial interfacial tension is delineated to favor miscibility or spontaneous emulsification, but it tends to revert to zero instantaneously. Furthermore, a slightly positive, initial interfacial tension can also lead to miscibility, if (pii)e can help reduce it to a zero equilibrium interfacial tension. We have also found a new important relationship between (pii)e and pie on the basis of the Laplace equation. We also attempt to calculate with our model the (pii)e's for at least 34 liquid pairs, by assuming the published interfacial tensions to be reasonable equilibrium values. Finally, the equilibrium spreading pressure pie for the liquid-solid interface, or the (pii)e for the liquid-liquid interface, appears to be the missing link between the wetting thermodynamics and linear free energy solvatochromic relationship (LFER). We have shown the pie or (pii)e of the former to be the equivalent of the Pi*, polarity/dipolarity parameter, of the latter. Our findings about the correlation between the surface tension component (STC) concept and LFER have provided a new support for the STC theory. Copyright 1999 Academic Press.}, } @article {pmid10221748, year = {1999}, author = {Furukawa, T and Yokouchi, T and Hirai, T and Kitamura, T and Takahashi, K}, title = {Parental loss in childhood and social support in adulthood among psychiatric patients. Group for Longitudinal Affective Disorders Study (GLADS).}, journal = {Journal of psychiatric research}, volume = {33}, number = {2}, pages = {165-169}, doi = {10.1016/s0022-3956(98)00054-5}, pmid = {10221748}, issn = {0022-3956}, mesh = {Adult ; Anxiety, Separation/psychology ; *Bereavement ; Female ; Humans ; Male ; Middle Aged ; Mood Disorders/*diagnosis/psychology ; Parent-Child Relations ; *Parents ; Psychiatric Status Rating Scales ; *Social Support ; Surveys and Questionnaires ; }, abstract = {Psychoanalytic theories hypothesize that early attachment experiences with parents shape the structure and function of adult interpersonal relationships. The present paper aims to examine if parental loss experiences in childhood is related to perceived social support in adulthood. We directly interviewed 1247 patients representative of 31 psychiatric clinics and hospitals all over Japan as to their parental loss experiences in childhood and also administered them Sarason et al.'s Social Support Questionnaire. It was found, to our surprise, that those who had lost the father or mother through death reported as many current support persons as those who had not and that those who had experienced separation from the mother (but not the father) reported greater satisfaction with social support than those who had not. Several hypotheses are advanced to explain these unexpected findings and it is concluded that we must at least entertain some doubt on the direct continuity hypothesis between disruptions of parent-child relationships and the individual's later capacity to enjoy social support.}, } @article {pmid10218259, year = {1999}, author = {Winsler, A and Díaz, RM and Espinosa, L and Rodríguez, JL}, title = {When learning a second language does not mean losing the first: bilingual language development in low-income, Spanish-speaking children attending bilingual preschool.}, journal = {Child development}, volume = {70}, number = {2}, pages = {349-362}, doi = {10.1111/1467-8624.t01-1-00026}, pmid = {10218259}, issn = {0009-3920}, mesh = {Achievement ; Analysis of Variance ; Case-Control Studies ; Child, Preschool ; Cultural Diversity ; Early Intervention, Educational/*methods ; Female ; Follow-Up Studies ; Humans ; *Language Development ; Male ; Mexican Americans/*education ; Minority Groups/education ; *Multilingualism ; Poverty ; }, abstract = {This article discusses two investigations which explored the bilingual language development outcomes of comparable groups of low-income, Spanish-speaking, Mexican American children who either did or did not attended a bilingual (Spanish/English) preschool. Study 1 is a replication of a study by Rodríguez, Díaz, Duran, and Espinosa, involving a new sample of 26 children who attended bilingual preschool for one year and 20 control children who remained at home. Study 2 represents a 1-year, longitudinal follow-up of Rodríguez et al.'s, sample of children during and after the children spent another year at home or in the preschool. In both investigations, standardized, objective measures of three components of children's language proficiency (productive language, receptive language, and language complexity) in English and Spanish were obtained at the beginning and end of the academic year. Contrary to fears that have been expressed by some that early exposure to English would lead to children's native language loss, the results of both studies offered no evidence of Spanish proficiency loss for children attending bilingual preschool. Children who attended bilingual preschool, compared to those who remained at home, showed significant and parallel gains in Spanish language development as well as significant and greater increases in English language proficiency over time. Results are discussed in terms of the need for more systematic research to be conducted in this area to inform policy and practice in the early education and development of language-minority children.}, } @article {pmid10217002, year = {1999}, author = {Ben Amor, H and Kallel, S and Karray, S and Saadaoui, F and Zouari, M and Litaiem, T and Douik, M}, title = {[Consequences of tibiotalar arthrodesis on the foot. A retrospective study of 36 cases with 8.5 years of followup].}, journal = {Acta orthopaedica Belgica}, volume = {65}, number = {1}, pages = {48-56}, pmid = {10217002}, issn = {0001-6462}, mesh = {Adult ; *Arthrodesis ; Female ; Foot Deformities, Congenital/pathology/*surgery ; Humans ; Joint Instability ; Male ; Osteoarthritis/surgery ; Retrospective Studies ; Subtalar Joint/pathology/*surgery ; Tibia/*surgery ; Treatment Outcome ; }, abstract = {The authors report the results of a retrospective study of 36 cases of tibiotalar arthrodesis performed in 22 men and 14 women with an average age of 32 years. All patients were reviewed with an average of 8.5 years follow-up. The predominating etiologies were ankle osteoarthritis (15 cases) and neurologic deformities of the foot (13 cases). Arthrodesis was performed using the Meary technique in 60% of cases, using the Charnley technique in 20% and the Crawford-Adams technique or with clamps in the other cases. Fusion was obtained in 97% of cases. Long-term results were assessed using Duquennoy et al.'s scoring system. They were very good or good in 58% of cases, fair in 31% and poor in 11%. The study of distal repercussions of tibiotalar arthrodesis shows progressive deterioration of the subtalar joint in 70% of cases and appearance or increase of degenerative changes in 75% of cases. The final results of the procedure depend on this deterioration; the latter is related with the arthrodesis position. Midtalar joint is a compensation joint showing hypermobility in 40% of cases. Degenerative changes were limited and asymptomatic in 80% of cases. Based on the findings in this study and on the literature, we conclude that the foot should be fixed at 90 degrees or with less than 5 degrees of equinus, with 5 degrees of valgus and 10 to 15 degrees of external rotation.}, } @article {pmid10093032, year = {1999}, author = {Ismail, AR and Asfour, SS}, title = {Discrete wavelet transform: a tool in smoothing kinematic data.}, journal = {Journal of biomechanics}, volume = {32}, number = {3}, pages = {317-321}, doi = {10.1016/s0021-9290(98)00171-7}, pmid = {10093032}, issn = {0021-9290}, mesh = {Algorithms ; *Biomechanical Phenomena ; *Mathematical Computing ; }, abstract = {Motion analysis systems typically introduce noise to the displacement data recorded. Butterworth digital filters have been used to smooth the displacement data in order to obtain smoothed velocities and accelerations. However, this technique does not yield satisfactory results, especially when dealing with complex kinematic motions that occupy the low- and high-frequency bands. The use of the discrete wavelet transform, as an alternative to digital filters, is presented in this paper. The transform passes the original signal through two complementary low- and high-pass FIR filters and decomposes the signal into an approximation function and a detail function. Further decomposition of the signal results in transforming the signal into a hierarchy set of orthogonal approximation and detail functions. A reverse process is employed to perfectly reconstruct the signal (inverse transform) back from its approximation and detail functions. The discrete wavelet transform was applied to the displacement data recorded by Pezzack et al., 1977. The smoothed displacement data were twice differentiated and compared to Pezzack et al.'s acceleration data in order to choose the most appropriate filter coefficients and decomposition level on the basis of maximizing the percentage of retained energy (PRE) and minimizing the root mean square error (RMSE). Daubechies wavelet of the fourth order (Db4) at the second decomposition level showed better results than both the biorthogonal and Coiflet wavelets (PRE = 97.5%, RMSE = 4.7 rad s-2). The Db4 wavelet was then used to compress complex displacement data obtained from a noisy mathematically generated function. Results clearly indicate superiority of this new smoothing approach over traditional filters.}, } @article {pmid10077301, year = {1999}, author = {Sato, T and Narita, T and Hirano, S and Kusunoki, K and Sakado, K and Uehara, T}, title = {Confirmatory factor analysis of the Parental Bonding Instrument in a Japanese population.}, journal = {Psychological medicine}, volume = {29}, number = {1}, pages = {127-133}, doi = {10.1017/s003329179800779x}, pmid = {10077301}, issn = {0033-2917}, mesh = {Adolescent ; Adult ; Aged ; Factor Analysis, Statistical ; Humans ; Japan ; Male ; Middle Aged ; *Object Attachment ; *Parent-Child Relations ; *Parenting ; Surveys and Questionnaires ; }, abstract = {BACKGROUND: There is controversy surrounding the factor structure of the Parental Bonding Instrument (PBI), a widely used instrument for assessing perceived parental rearing behaviours. Recent studies have proposed five different factor structures, including Parker et al.'s original two-factor model.

METHODS: Four hundred and eighteen employed Japanese adults filled out the PBI. Maximum likelihood confirmatory factor analyses were performed to compare the five different factor structures in terms of model-fit.

RESULTS: Parker's original two-factor structure fitted the data poorly. In general, three-factor structures showed better fit. Among the three-factor structures, Murphy's model and Kendler's model were superior (the adjusted goodness-of-fit index > 0.8), with the latter providing the best fit to the data (the goodness-of-fit index > 0.9). When considering invariance of factor structure across gender subgroups and across age subgroups, only Kendler's model was acceptable.

CONCLUSIONS: Parker's two-factor structure of the PBI may not be appropriate for assessing perceived parental rearing behaviours in a Japanese population. Three-factor structures, in particular Murphy's model and Kendler's model, are preferable. Kendler's model provided the best fit to the data and was relatively invariant across the subgroups in this study. Thus, Kendler's model might prove to be very important for obtaining a factor structure invariant across different cultures.}, } @article {pmid10052095, year = {1998}, author = {Greenberg, AC}, title = {Further comments regarding Malik, et al.'s 1996 experiment on the method of subliminal psychodynamic activation.}, journal = {Perceptual and motor skills}, volume = {87}, number = {3 Pt 2}, pages = {1369-1370}, doi = {10.2466/pms.1998.87.3f.1369}, pmid = {10052095}, issn = {0031-5125}, mesh = {*Communication ; Fantasy ; Humans ; Models, Psychological ; Mother-Child Relations ; *Research Design ; *Subliminal Stimulation ; }, abstract = {Further comments focus on the use of partial and anagram messages and the need for neutral stimuli in establishing subjective thresholds for subliminal psychodynamic activation.}, } @article {pmid10047440, year = {1999}, author = {Goswami, U}, title = {Orthographic analogies and phonological priming: a comment on Bowey, Vaughan, and Hansen (1998).}, journal = {Journal of experimental child psychology}, volume = {72}, number = {3}, pages = {210-219}, doi = {10.1006/jecp.1998.2483}, pmid = {10047440}, issn = {0022-0965}, mesh = {Association ; Child ; Child Development/*physiology ; Cues ; Female ; Humans ; Male ; Phonetics ; Psycholinguistics/*methods ; *Reading ; *Research Design ; Verbal Learning ; }, abstract = {J. A. Bowey, L. Vaughan, and J. Hansen (1998, Journal of Experimental Child Psychology, 68, 108-133) carried out two experiments on 6- and 7-year-old children's use of orthographic analogies in word reading. They reported that, following apparently stringent controls for phonological priming effects, beginning analogies (beak-bean) were more frequent in this age group than rime (beak-peak) analogies. From this, they concluded that beginning readers do not reliably use orthographic rimes in reading, even in the clue word task (p. 129). However, the clue word task was not used in this study. This comment highlights two problems with Bowey et al.'s paper. The first is a theoretical one, and the second is methodological. Firstly, Bowey et al. base their investigation on a misunderstanding of U. Goswami and P. E. Bryant's (1990, Phonological skills and learning to read, Hillsdale, NJ: Erlbaum) claims about the role of rhyme and analogy in beginning reading. Secondly, methodological weaknesses, in particular unintended intralist priming effects, seriously limit the conclusions that can be drawn from Bowey et al.'s booklet analogy task.}, } @article {pmid9988378, year = {1999}, author = {Eller, E}, title = {Population substructure and isolation by distance in three continental regions.}, journal = {American journal of physical anthropology}, volume = {108}, number = {2}, pages = {147-159}, doi = {10.1002/(SICI)1096-8644(199902)108:2<147::AID-AJPA2>3.0.CO;2-E}, pmid = {9988378}, issn = {0002-9483}, mesh = {Alleles ; *Genetics, Population ; Geography ; Heterozygote ; Humans ; Models, Genetic ; Tandem Repeat Sequences/*genetics ; }, abstract = {Isolation by distance and divergence from a shared population history are two sources of population substructure. Isolation by distance erases population history as populations approach migration-drift equilibrium, while diverging populations descended from a single ancestral population will accumulate genetic differences with time. Here I investigate how much of the worldwide genetic diversity from Jorde et al.'s ([1997] Proc. Natl. Acad. Sci. USA 94:3100-3103) 60 tetranucleotide short tandem repeat (STR) data can be explained by isolation by distance. I use Slatkin's measure of population substructure, R(ST), principal components analyses, and Mantel tests to investigate the pattern of genetic diversity at both the intercontinental and intracontinental levels. Geographic distance accounts for almost 60% of world-wide interpopulation genetic relationships. Within continents, the correlations are less, although not significantly so because of wide confidence intervals. These results suggest that populations have not reached migration-drift equilibrium and that there is information in STR data to reconstruct population history. The level of population substructure worldwide is consistent with previous observations, but at the intracontinental level substructure is less. When one examines diversity against distance from the centroid, one sees excess heterozygosity in Africa, a pattern also noted by Stoneking et al. ([1998] Genome Research 7:1061-1071). A larger effective population size in Africa could explain the excess diversity. Greater gene flow in Africa is an unlikely explanation because the African R(ST) value is slightly larger than the Asian and European R(ST)s, pointing to less gene flow and greater substructure among African populations. Furthermore, there are differences in patterns between heterozygosity and allele size variance. Heterozygosity has a higher correlation with distance from the centroid than does allele size variance, and this may reflect demographic history. Kimmel et al. ([1998] Genetics 148:1921-1930) have shown that after a population expansion heterozygosity returns to equilibrium more quickly than does allele size variance. The contrasting patterns between heterozygosity and allele size variance may reflect different times after an expansion. However, simulations and further work need to be done to more thoroughly investigate the possibility that these data reflect population expansions.}, } @article {pmid9923178, year = {1998}, author = {Yamada, J and Takashima, H and Yamazaki, M}, title = {Effect of ease-of-acquisition on naming latency for Japanese kanji: a reanalysis of Yamazaki, et al.'s (1997) data.}, journal = {Psychological reports}, volume = {83}, number = {3 Pt 1}, pages = {991-1002}, doi = {10.2466/pr0.1998.83.3.991}, pmid = {9923178}, issn = {0033-2941}, mesh = {Adolescent ; Adult ; Age Factors ; Child ; Female ; Humans ; Japan ; *Language ; Male ; *Reaction Time ; *Reading ; *Verbal Learning ; }, abstract = {Yamazaki, Ellis, Morrison, and Lambon Ralph in 1997 found two age-of-acquisition measures exerted greater independent effects on the naming latency of kanji than well-established variables such as word frequency. The current study is a sequel to that study but has reached a different conclusion. To find a better predictor than the two age-of-acquisition measures, Yamazaki, et al.'s data were reanalyzed with the new variable, ease-of-acquisition. The main finding was that the correlation between ease-of-acquisition at age 13 and naming latency was high .67 (df = 145, p < .001). The status of ease-of-acquisition and its possible role in psycholinguistic research are briefly discussed.}, } @article {pmid9883307, year = {1998}, author = {Blanchard, R and Bogaert, AF}, title = {Birth order in homosexual versus heterosexual sex offenders against children, pubescents, and adults.}, journal = {Archives of sexual behavior}, volume = {27}, number = {6}, pages = {595-603}, doi = {10.1023/a:1018773117741}, pmid = {9883307}, issn = {0004-0002}, mesh = {Adolescent ; Adult ; *Birth Order ; Child ; Child, Preschool ; Homosexuality, Male/*psychology ; Humans ; Male ; *Sex Offenses ; }, abstract = {Homosexual men erotically attracted to physically mature partners typically have more older brothers than comparable heterosexual men. We investigated whether late fraternal birth positions also occur in homosexuals attracted to children or pubescents. Probands were 710 sex offenders from Gebhard et al.'s (1965) study of sexual offending. Homosexual offenders against adults and pubescents had later fraternal birth positions than heterosexual offenders against adults and pubescents, respectively; there was no difference between the homosexual and heterosexual offenders against children. Results provide some evidence that homosexuality in men attracted to immature males is etiologically related to homosexuality in men attracted to mature males.}, } @article {pmid9855278, year = {1998}, author = {Debruille, JB and Guillem, F and Renault, B}, title = {ERPs and chronometry of face recognition: following-up Seeck et al. and George et al.}, journal = {Neuroreport}, volume = {9}, number = {15}, pages = {3349-3353}, doi = {10.1097/00001756-199810260-00002}, pmid = {9855278}, issn = {0959-4965}, mesh = {Adult ; Analysis of Variance ; Evoked Potentials, Visual/*physiology ; *Face ; Female ; Humans ; Male ; Pattern Recognition, Visual/*physiology ; Reaction Time/*physiology ; Time Factors ; Visual Cortex/*physiology ; }, abstract = {Seeck et al. found that event-related potentials (ERPs) evoked by repeated and non-repeated face photographs differ as early as 50-70ms post-onset. They thus suggested that faces are recognized at these latencies, in contrast with current opinions in ERP literature. However, the similar latencies obtained by George et al. for stimuli not perceived as faces suggest that Seeck et al.'s differences could index repetition rather than face recognition per se. To address this issue, we used matched faces of known and unknown persons. We found the earliest differences between the ERPs to these faces between 76 and 130 ms. These results, which are consistent with other data, suggest that the differentiation of faces takes approximately 100 ms of processing time in humans.}, } @article {pmid9850476, year = {1998}, author = {Frisbie, WP and Forbes, D and Hummer, RA and Pullum, SG}, title = {Birth outcome, not pregnancy process: reply to van der Veen.}, journal = {Demography}, volume = {35}, number = {4}, pages = {519-527}, pmid = {9850476}, issn = {0070-3370}, support = {R01-HD32330/HD/NICHD NIH HHS/United States ; }, mesh = {Birth Weight ; Female ; Fetal Growth Retardation/ethnology ; Humans ; *Infant Mortality ; Infant, Newborn ; Pregnancy ; Pregnancy Outcome/*ethnology ; Risk Factors ; United States/epidemiology ; }, abstract = {In a recent article (Frisbie, Forbes, and Pullum 1996) we documented racial/ethnic differences in birth outcomes according to a more fine-grained classification than has typically been employed in the demographic literature. In his commentary, van der Veen focuses on the measurement of one of the dimensions of that classification, maturity of the infant, as proxied by the fetal growth ratio. The crux of the critique is easily seen in van der Veen's statement that "all of my disagreements with Frisbie et al.'s method arise from their particular use of a postnatal standard for the assessment of intrauterine growth." Our critic misunderstands our objective: He fails to realize our interest in birth outcome, not pregnancy process, and does not perceive that our intent was to extend the research extant in both the demographic and public-health literatures in which patently postnatal (i.e., ex utero) measures are taken as outcomes interesting in their own right and/or as risk factors for infant mortality and infant and childhood morbidity. Specifically, he does recognize that we purposefully expanded our focus to include moderately compromised births to determine if they were at higher risk than the normal births with whom they are conventionally categorized. Our discussion draws on research cited in the original article, on studies cited by our critic, and on a few more recent investigations. Although we have never argued that ours is the only, or even the best approach in all cases, we try to clarify the rationale for, and adduce additional empirical evidence of, the utility of the method we used.}, } @article {pmid9850475, year = {1998}, author = {van der Veen, WJ}, title = {Comment on "Compromised birth outcomes and infant mortality among racial and ethnic groups".}, journal = {Demography}, volume = {35}, number = {4}, pages = {509-517}, pmid = {9850475}, issn = {0070-3370}, mesh = {*Black or African American/statistics & numerical data ; Birth Weight ; Cohort Studies ; Female ; Fetal Growth Retardation/ethnology ; Gestational Age ; Humans ; *Infant Mortality ; Infant, Newborn ; Pregnancy ; Pregnancy Outcome/*ethnology ; United States/epidemiology ; *White People/statistics & numerical data ; }, abstract = {Frisbie, Forbes, and Pullum (1996) show that it is meaningful to account for low birth weight, preterm delivery, and intrauterine growth-retardation when analyzing differences in compromised birth outcomes and infant mortality among racial and ethnic groups. I compare their findings for the 1987 U.S. birth cohort with findings for the 1988 U.S. birth cohort, using linked birth and infant death vital statistics from the National Center for Health Statistics. I focus on their calculation of fetal growth curves, which are highly at odds with the curves commonly used in the obstetric and pediatric literature. I compare birth outcome distributions and infant death probabilities using Frisbie et al.'s method and other standards. I conclude that Frisbie et al.'s method is not suited for the study of intrauterine growth-retardation at the population level because of the major flaws in gestational age measurement that exist in the type of data they use. An appropriate alternative is to apply a standard of normal intrauterine growth derived from antenatal estimation of fetal weight-for-gestational-age to the vital statistics data.}, } @article {pmid9787044, year = {1998}, author = {Dugatkin, LA}, title = {A comment on Lafleur et al.'s re-evaluation of mate-choice copying in guppies.}, journal = {Animal behaviour}, volume = {56}, number = {2}, pages = {513-514}, doi = {10.1006/anbe.1998.0804}, pmid = {9787044}, issn = {0003-3472}, } @article {pmid9827248, year = {1998}, author = {Obelieniene, D and Bovim, G and Schrader, H and Surkiene, D and Mickeviàiene, D and Miseviàiene, I and Sand, T}, title = {Headache after whiplash: a historical cohort study outside the medico-legal context.}, journal = {Cephalalgia : an international journal of headache}, volume = {18}, number = {8}, pages = {559-564}, doi = {10.1046/j.1468-2982.1998.1808559.x}, pmid = {9827248}, issn = {0333-1024}, mesh = {Accidents, Traffic ; Adult ; Cohort Studies ; Female ; Headache/epidemiology/*etiology ; Humans ; Lithuania/epidemiology ; Male ; Middle Aged ; Time Factors ; Whiplash Injuries/*complications ; }, abstract = {Headache is frequently reported as a chronic complaint after whiplash traumas. Criteria have been presented, but it has not been validated whether any specific headache type emerges after a trauma with whiplash mechanism. In a questionnaire-based historical cohort design, 202 adult Lithuanian individuals were interviewed 1-3 years after experiencing a rear-end car collision. The questionnaire was designed so that a diagnosis of migraine and tension-type headache in accordance with the International Headache Society criteria could be made. "Possible cervicogenic headache" was diagnosed according to Sjaastad et al.'s minimal criteria. The diagnostic panorama in those with traumas was compared with that of an age- and sex-matched control group. The introductory questions did not reveal differences in headache frequencies between the traumatized and control groups (p = 0.60). The prevalence of migraine and tension-type headache (both episodic and chronic) was also similar. A higher frequency of possible cervicogenic headache was observed in the traumatized group (10 vs 5), but the difference was not statistically significant (p = 0.28). Sixteen patients in the accident group had headache > 15 days per month, 11 of the 16 had similar complaints before the trauma, while 5 had worsened headache as compared to (the recollected headache) before the trauma. None of the patients with possible cervicogenic headache reported increased headache after the accident. Accordingly, the present results obtained outside the medico-legal context do not confirm that a specific headache pattern emerges 1-3 years after a rear-end car collision.}, } @article {pmid9822792, year = {1998}, author = {Sidossis, LS}, title = {The role of glucose in the regulation of substrate interaction during exercise.}, journal = {Canadian journal of applied physiology = Revue canadienne de physiologie appliquee}, volume = {23}, number = {6}, pages = {558-569}, doi = {10.1139/h98-031}, pmid = {9822792}, issn = {1066-7814}, mesh = {Animals ; Energy Metabolism/*physiology ; Exercise/*physiology ; Fatty Acids/physiology ; Glucose/*physiology ; Humans ; }, abstract = {Glucose and fatty acids are the main energy sources for oxidative metabolism in endurance exercise. Although a reciprocal relationship exists between glucose and fatty acid contribution to energy production for a given metabolic rate, the controlling mechanism remains debatable. Randle et al.'s (1963) glucose-fatty acid cycle hypothesis provides a potential mechanism for regulating substrate interaction during exercise. The cornerstone of this hypothesis is that the rate of lipolysis, and therefore fatty acid availability, controls how glucose and fatty acids contribute to energy production. Increasing fatty acid availability attenuates carbohydrate oxidation during exercise, mainly via sparing intramuscular glycogen. However, there is little evidence for a direct inhibitory effect of fatty acids on glucose oxidation. We found that glucose directly determines the rate of fat oxidation by controlling fatty acid transport into the mitochondria. We propose that the intracellular availability of glucose, rather than fatty acids, regulates substrate interaction during exercise.}, } @article {pmid9820435, year = {1998}, author = {Zagnoon, A}, title = {Dr. Bethge et al.'s case on stent use.}, journal = {The American journal of gastroenterology}, volume = {93}, number = {11}, pages = {2311-2312}, doi = {10.1111/j.1572-0241.1998.02311.x}, pmid = {9820435}, issn = {0002-9270}, mesh = {Aged ; Humans ; Male ; Palliative Care ; Pyloric Stenosis/*therapy ; *Stents ; }, } @article {pmid9820028, year = {1998}, author = {Kakizuka, A}, title = {Protein precipitation: a common etiology in neurodegenerative disorders?.}, journal = {Trends in genetics : TIG}, volume = {14}, number = {10}, pages = {396-402}, doi = {10.1016/s0168-9525(98)01559-5}, pmid = {9820028}, issn = {0168-9525}, mesh = {Chemical Precipitation ; Humans ; Inclusion Bodies ; Neurodegenerative Diseases/*etiology/metabolism ; Peptides/*metabolism ; Proteins/chemistry/*metabolism ; Trinucleotide Repeats ; }, abstract = {Molecular genetic analyses have elucidated a class of inherited neurodegenerative disorders caused by expanded CAG repeats encoding polyglutamines (e.g. Huntington disease and Machado-Joseph disease). Proteins containing expanded polyglutamine repeats appear to precipitate by self-aggregation and, as a result, produce a core disease-related phenotype: neuronal cell death or degeneration. In other neurodegenerative disorders, such as Alzheimer disease, prion disease, Parkinson disease and amyotrophic lateral sclerosis, precipitation of abnormal proteins is also now considered to play a key role. These observations might lead to the elucidation of universal mechanisms for neurodegeneration and to effective treatments for many neurodegenerative disorders.}, } @article {pmid9811603, year = {1998}, author = {He, S and Cohen, ER and Hu, X}, title = {Close correlation between activity in brain area MT/V5 and the perception of a visual motion aftereffect.}, journal = {Current biology : CB}, volume = {8}, number = {22}, pages = {1215-1218}, doi = {10.1016/s0960-9822(07)00512-x}, pmid = {9811603}, issn = {0960-9822}, support = {R01 MH55346/MH/NIMH NIH HHS/United States ; }, mesh = {Adaptation, Physiological/*physiology ; Brain/*physiology ; Female ; Humans ; Male ; Motion Perception/*physiology ; Visual Perception/*physiology ; }, abstract = {Studies in primate physiology and human functional neuroimaging have convincingly shown that the area of the brain termed MT/V5(+)-which includes the middle temporal visual area MT/V5 along with adjacent motion-sensitive areas such as MST--is involved in the processing of motion information [1,2]. Tootell et al. [3] showed that the blood oxygenation level dependent (BOLD) signal measured by functional magnetic resonance imaging (fMRI) in the human MT/V5+ seemingly correlates with the strength of perceived motion aftereffect (MAE), the illusory motion of a stationary pattern that one sees after adapting to a moving pattern [4]. The signal in MT/V5+ decayed slowly during the period when the MAE was seen. It is possible that this slow decrease in MT/V5+ activity was unrelated to the perceptual experience of motion. After replicating Tootell et al.'s experiment, a modified version of the experiment was conducted in which a blank period was inserted between the adapting motion stimulus and the stationary testing pattern. The results demonstrated that MT/V5+ activity indeed decayed more slowly after an effective unidirectional motion adaptation than after bidirectional adaptation, without corresponding perception of MAE. Nevertheless, in a more conclusive experiment, we adapted observers to a unidirectional motion for a very long period and showed that the activity in MT/V5+ changed in synchrony with the presence and absence of perceived MAE, simply as a result of presenting a stationary visual stimulus in and out of the adapted retinal region.}, } @article {pmid9809327, year = {1998}, author = {Fox, BH}, title = {A hypothesis about Spiegel et al.'s 1989 paper on Psychosocial intervention and breast cancer survival.}, journal = {Psycho-oncology}, volume = {7}, number = {5}, pages = {361-370}, doi = {10.1002/(SICI)1099-1611(1998090)7:5<361::AID-PON347>3.0.CO;2-U}, pmid = {9809327}, issn = {1057-9249}, mesh = {Breast Neoplasms/*psychology ; Confounding Factors, Epidemiologic ; Female ; Humans ; Mathematical Computing ; *Psychotherapy, Group ; Reproducibility of Results ; *SEER Program ; *Social Support ; Survival Analysis ; }, abstract = {In a randomized prospective study of 86 metastatic breast cancer patients by Spiegel et al. in 1989, the 50 who took part in a group psychosocial intervention survived on average 18 months longer than the 36 controls who did not. Because the control survival curve looked unusually steep, lacking an expected right-skewed tail, both curves were compared with that of a population from the same region having metastatic breast cancer. When transformed to life-table format, the curves of the control sample and the regional population, neither group having had an intervention, were almost identical for a year, and differed strikingly after 20 months. This led to the hypothesis that the 12 control patients surviving for more than 20 months were an extremely aberrant sample, being subject to the strong biasing influence of possible confounders, of which a considerable number are known, but not including those accounted for in the study. Corollaries to the hypothesis are that the intervention had no effect; that the intervention curve was in fact equivalent to a control curve with mild sampling departure from that of the regional population; and that, therefore, the repetition of the study now under way would not yield confirmation of the 1989 study, but rather, would support the hypothesis and the first two corollaries.}, } @article {pmid9787054, year = {1998}, author = {Carey, DP and Dijkerman, HC and Milner, AD}, title = {Perception and action in depth.}, journal = {Consciousness and cognition}, volume = {7}, number = {3}, pages = {438-453}, doi = {10.1006/ccog.1998.0366}, pmid = {9787054}, issn = {1053-8100}, support = {//Wellcome Trust/United Kingdom ; }, mesh = {Agnosia/physiopathology ; Depth Perception/*physiology ; Female ; Humans ; *Mental Processes ; Visual Cortex/pathology/*physiology ; }, abstract = {Little is known about distance processing in patients with posterior brain damage. Although many investigators have claimed that distance estimates are normal or abnormal in some of these patients, many of these observations were made informally and the examiners often asked for relative, and not absolute, distance estimates. The present investigation served two purposes. First, we wanted to contrast the use of distance information in peripersonal space for perceptual report as opposed to visuomotor control in our visual form agnosic patient, DF. Second, we wanted to see to what extent her abilities to process distance cues were dependent on binocular vision, in light of Milner et al.'s (1991) observations of preserved stereopsis in DF, and Dijkerman et al.'s (1996) and Marotta et al.'s (1997) observations that her visual guidance of grasping may be particularly dependent on binocular vision of the target. We hypothesized that DF's visuomotor responses would show normal sensitivity to target distance, while her perceptual estimates would not. In the first experiment, we required DF and two age- and sex-matched control subjects to reach out and grasp black cubes placed at varying distances, or to estimate the distance of the cubes from the hand starting position without making a reaching movement. In the second experiment, we required DF and two age-matched control subjects to point as rapidly and accurately as possible to small LED targets which differed in spatial location, under binocular and monocular conditions. The results showed that, relative to the control subjects, DF's grasping movements produced normal peak velocity-distance scaling-when she reached for blocks which varied in depth or pointed to LED targets which were presented at different distances in depth. In contrast, in the cube experiment, her verbal estimates of object distance were poorly scaled, although they improved slightly under the binocular conditions. The results are discussed in terms of current theories of processing streams in extrastriate visual cortex and the distinction between categorical and coordinate spatial processing.}, } @article {pmid9779248, year = {1998}, author = {Guarrera, M and Ferrari, P and Rebora, A}, title = {Catalase in the stratum corneum of patients with polymorphic light eruption.}, journal = {Acta dermato-venereologica}, volume = {78}, number = {5}, pages = {335-336}, doi = {10.1080/000155598442999}, pmid = {9779248}, issn = {0001-5555}, mesh = {Adolescent ; Adult ; Aged ; Catalase/*metabolism ; Epidermis/*enzymology/pathology ; Female ; Humans ; Male ; Middle Aged ; Photosensitivity Disorders/*enzymology ; Skin/enzymology/pathology ; }, abstract = {UV radiation generates reactive oxygen species, which may be involved in polymorphic light eruption. The endogenous enzymatic defense system includes catalase in the epidermis. Thirteen patients with a history of polymorphic light eruption, but free from lesions, and 13 controls were investigated from November to March. Catalase was analysed in the upper horny layer according to Colin et al.'s spectrophotometric technique. In polymorphic light eruption, catalase values were about 30% lower than in control subjects. Such deficiency was observed in patients free from the disease and not recently sun-exposed. The diminished skin catalase in irradiated polymorphic light eruption makes it possible that a longer restoration time of catalase is involved in the pathogenesis.}, } @article {pmid9760663, year = {1998}, author = {Malik, R}, title = {Reply to Greenberg's critique of Malik, et al.'s experiment on the method of subliminal psychodynamic activation.}, journal = {Perceptual and motor skills}, volume = {87}, number = {1}, pages = {313-314}, doi = {10.2466/pms.1998.87.1.313}, pmid = {9760663}, issn = {0031-5125}, mesh = {Female ; Humans ; Mental Recall ; *Reading ; Research Design/standards ; Semantics ; Sensory Thresholds ; *Subliminal Stimulation ; *Unconscious, Psychology ; *Visual Perception ; }, abstract = {Greenberg raised two issues concerning an experiment reported by Malik, et al. on the method of subliminal psychodynamic activation. One relates to the appropriateness of control and threshold stimuli and the other to the use of subjective thresholds. Both concerns are addressed.}, } @article {pmid9725757, year = {1998}, author = {Buffett-Jerrott, SE and Stewart, SH and Teehan, MD}, title = {A further examination of the time-dependent effects of oxazepam and lorazepam on implicit and explicit memory.}, journal = {Psychopharmacology}, volume = {138}, number = {3-4}, pages = {344-353}, doi = {10.1007/s002130050680}, pmid = {9725757}, issn = {0033-3158}, mesh = {Adult ; Analysis of Variance ; Attention/drug effects ; Cognition Disorders/physiopathology ; Conscious Sedation ; Cues ; Double-Blind Method ; Female ; Humans ; Hypnotics and Sedatives/pharmacology ; Lorazepam/*pharmacology ; Male ; Memory/*drug effects ; Mental Recall/drug effects ; Motion Pictures ; Oxazepam/*pharmacology ; Psychomotor Performance/drug effects ; Time Factors ; }, abstract = {Until recently, research indicated that all benzodiazepines impair explicit memory, while only lorazepam impairs priming. Stewart and associates provided preliminary data which indicated that both oxazepam and lorazepam may impair implicit memory, but in a time-dependent fashion. The present study was designed to replicate Stewart et al.'s findings after overcoming several limitations of the original study. Thirty subjects were administered an acute dose of lorazepam (2 mg), oxazepam (30 mg) or a placebo and were tested with an implicit (word-stem completion) test and an explicit (cued recall) test. However, subjects were only tested at 170 min post-drug (close to oxazepam's theoretical peak concentration) to rule out the possible "explicit memory contamination" explanation of the Stewart et al. implicit memory findings. Consistent with previous research, both drugs impaired explicit memory relative to placebo. Also, both lorazepam and oxazepam impaired priming performance, supporting the "time-dependence" interpretation of the Stewart et al. findings. The results also indicate that episodic memory is impaired by both benzodiazepines in a time-dependent fashion even when the research methodology used involves everyday memory demands.}, } @article {pmid9720121, year = {1998}, author = {White, MS and Maher, BA and Manschreck, TC}, title = {Hemispheric specialization in schizophrenics with perceptual aberration.}, journal = {Schizophrenia research}, volume = {32}, number = {3}, pages = {161-170}, doi = {10.1016/s0920-9964(98)00057-7}, pmid = {9720121}, issn = {0920-9964}, mesh = {Adult ; Face ; *Functional Laterality ; Humans ; Male ; Mental Recall ; Perceptual Disorders/physiopathology ; Schizophrenia/*physiopathology ; }, abstract = {Higher rates of left-handedness and atypical lateralization in schizophrenics paired with findings of morphological abnormalities in cerebral asymmetry suggest that the normal patterns of hemisphere specialization for processing verbal and spatial information may be anomalous in schizophrenics. The small number of studies that have addressed this question have produced inconsistent findings and varied with subtype diagnosis, gender, type of task employed, task difficulty, and control of handedness. Conflicting research findings also may be due to confounding from the heterogeneity of the schizophrenic construct and variability in clinical symptoms across patients. The present study was designed to control for factors that may have confounded earlier studies. Because the study used perceptual measures, the relationship between symptoms of perceptual aberration and hemisphere advantages was examined using Chapman et al.'s (1978) Perceptual Aberration Scale (PAS). Fifteen male schizophrenic patients and 14 male controls were administered tachistoscopic letter and facial recognition go/no-go reaction time tasks. Left hemisphere advantages were found for both controls and schizophrenics on the letter task. Right hemisphere advantages were found for controls on the facial task but not schizophrenics. Instead, a strong negative correlation was found between schizophrenics' PAS scores and hemisphere advantages (r = -0.685, p < 0.007). Further analysis identified a subgroup of schizophrenics with perceptual aberration who exhibited reversed left hemisphere advantages that increased as the PAS scores increased. Additional research is needed to determine whether this subgroup of schizophrenics constitutes a meaningful subtype with a distinct disease process that disrupts the development of normal cerebral lateralization. The findings provide further evidence for the importance of examining relationships between schizophrenics' performance on cognitive measures and their symptom patterns.}, } @article {pmid9709530, year = {1998}, author = {Bruhn, AR}, title = {Early memories and maladjustment: comment on Spirrison, et al. and recalled age of earliest memory.}, journal = {Psychological reports}, volume = {82}, number = {3 Pt 2}, pages = {1287-1292}, doi = {10.2466/pr0.1998.82.3c.1287}, pmid = {9709530}, issn = {0033-2941}, mesh = {Age Factors ; Child ; Child, Preschool ; Female ; Humans ; Male ; Mental Recall/*physiology ; *Social Adjustment ; }, abstract = {Spirrison, Schneider, Hartwell, Carmack, and D'Reaux (1997) argued that onset prior to age 4 of reported first memory is linked to maladjustment based on a study of 60 undergraduates; however, the literature suggests that sex, age, socioeconomic status, and Verbal IQ are likely to affect age of first recall. Responses of three previously unanalyzed samples were then reviewed for age of first recall The first two samples yielded a .3-year earlier age of first recall for the female university student sample (3.2 vs 3.5 yr. for men); however, Spirrison, et al.'s prediction of maladjustment is probably better explained by various personal and demographic variables. A third sample--incarcerated male prisoners--was handpicked for specific demographic measures to test the notion that late age of first recall is linked with somatic complaints. Their average age of first recall was 6.2 yr. or "late onset." Spirrison, et al.'s results would predict "somatic concerns"--extremely unlikely for this group. First recall at a later age is likely linked to a variety of psychological and demographic variables, including but not limited to low Verbal IQ, low education, low socioeconomic status, male, and a criminal background. Similarly, early age of first recall is probably linked to a high Verbal IQ, high education, middle-class socioeconomic status or higher, female, and an interest in reflection, among other variables. More research is needed on what affects age of first recall to avoid questionable attributions of pathology.}, } @article {pmid9696914, year = {1998}, author = {Mourad, I and Lejoyeux, M and Adès, J}, title = {[Prospective evaluation of antidepressant discontinuation].}, journal = {L'Encephale}, volume = {24}, number = {3}, pages = {215-222}, pmid = {9696914}, issn = {0013-7006}, mesh = {Adult ; Aged ; Aged, 80 and over ; Antidepressive Agents/*adverse effects/therapeutic use ; Depressive Disorder/*drug therapy/psychology ; Female ; Humans ; Male ; Middle Aged ; Neurologic Examination/drug effects ; Prospective Studies ; Psychiatric Status Rating Scales ; Substance Withdrawal Syndrome/*diagnosis/psychology ; }, abstract = {The authors prospectively assessed symptoms induced by the interruption of antidepressants in 16 patients (11 women and 5 men), aged from 33 to 85 years (mean = 52.4 +/- 16.4), treated with antidepressants since at least two weeks. All patients were free of alcohol abuse or dependence disorder and of other dependence to psychoactive substances. None of them presented medical illness. Diagnosis were made by separate evaluations by two authors and confirmed with a semistructered assessment instrument: the Schedule for Affective Disorders and Schizophrenia (Lifetime Version). All patients were submitted to a brutal discontinuation of their antidepressant agent. Patients were assessed twice, before the interruption of the antidepressant, and 72 hours later. Effects of antidepressant interruption were assessed by several means. Modification of anxiety and depression were evaluated using the Montgomery Asberg Depression Rating Scale (MADRS) and the Hamilton Anxiety Scale. Symptoms of withdrawal were assessed with Cassano and al.'s scale SESSH including an evaluation of anxiety, agitation, irritability, anergy, difficulty on concentrating, depersonalization, sleep and appetite disorders, muscle pains, nausea, tremor, sweating, altered taste, hyperosmia, paresthesias, photophobia, motor incoordination, dizziness, hyperacousia pain, delirium. Fourteen of the 16 patients (87.5%) presented modifications of their somatic or psychic state 3 days after the interruption of the antidepressant treatment. Most frequent symptoms were: increase in anxiety (31%), increase in irritability (25%), sleep disorders (19%), decrease of anergia and fatigue (19%). Mean scores of anxiety and depression were not significantly modified by the withdrawal. Following TCAs interruption (7 patients) most frequent symptoms were sleep disorders; increase in anxiety, nausea. Among patients withdrawn from SSRIs (6 patients), most frequent symptoms were increase in anxiety, increase in irritability, headache. Patients also presented a decrease of nausea, and of anorexia.}, } @article {pmid9687849, year = {1998}, author = {Christianson, AL and Viljoen, DL and Winship, WS and de la Rey, M and van Rensburg, EJ}, title = {Prader-Willi syndrome in South African patients--clinical and molecular diagnosis.}, journal = {South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde}, volume = {88}, number = {6}, pages = {711-714}, pmid = {9687849}, issn = {0256-9574}, mesh = {Blotting, Southern ; Chromosome Deletion ; Chromosomes, Human, Pair 15/genetics ; DNA Probes ; Female ; Humans ; Male ; Methylation ; Nucleic Acid Hybridization ; Prader-Willi Syndrome/*diagnosis/genetics ; Prospective Studies ; South Africa ; }, abstract = {STUDY OBJECTIVE: To assess clinically South African patients with the putative diagnosis of Prader-Willi syndrome (PWS) and confirm this diagnosis by DNA/molecular analysis.

DESIGN: Prospective, nationally based, combined clinical and laboratory study.

MAIN RESULTS: Thirty-seven patients with a putative diagnosis of PWS were examined by clinical geneticists. Only 13 (35.1%) of these patients had the diagnosis of PWS confirmed by molecular analysis, and all 13 PWS patients had positive scores using the PWS consensus diagnostic criteria of Holm et al. The clinical features of the remaining 24 (64.9%) non-PWS patients were analysed and 23 did not have the neonatal, infantile and childhood features necessary to warrant consideration of a diagnosis of PWS; neither did they obtain a positive score according to Holm et al.'s criteria.

CONCLUSION: PWS was confirmed in only 35% of South African patients with a putative PWS diagnosis, confirming that this condition is overdiagnosed and that the clinical diagnosis is difficult. Clinically, the diagnostic criteria of Holm et al. are of great assistance in making the diagnosis, but it remains essential to confirm the diagnosis by molecular analysis.}, } @article {pmid9680045, year = {1998}, author = {Lysaker, PH and Bell, MD and Bryson, GJ and Kaplan, E}, title = {Insight and interpersonal function in schizophrenia.}, journal = {The Journal of nervous and mental disease}, volume = {186}, number = {7}, pages = {432-436}, doi = {10.1097/00005053-199807000-00008}, pmid = {9680045}, issn = {0022-3018}, mesh = {Adult ; *Awareness ; Female ; Health Status ; Humans ; *Interpersonal Relations ; Male ; Psychiatric Status Rating Scales/statistics & numerical data ; Psychometrics ; Quality of Life ; Reproducibility of Results ; Schizophrenia/*diagnosis ; *Schizophrenic Psychology ; Social Adjustment ; }, abstract = {Research has linked impaired insight in schizophrenia to poorer medication compliance and treatment outcome. It is unclear, however, whether poorer interpersonal function is also associated with impaired insight. To examine this question, subjects with schizophrenia or schizoaffective disorder were classified as having unimpaired (N = 44) or impaired (N = 57) insight, and their scores on Heinrichs et al.'s Quality of Life (QOL) Scale were compared. Multiple regressions were conducted to determine the relationship between individual components and social function. Results indicate that subjects with impaired insight had significantly poorer QOL interpersonal relation and intrapsychic foundation scores than unimpaired subjects, despite having equivalent deficit symptoms. Unawareness of the social consequences of illness was found to be the component of insight more closely linked to social dysfunction. This suggests that impairments in insight may be uniquely associated with social dysfunction.}, } @article {pmid9676454, year = {1998}, author = {Sugano, N and Noble, PC and Kamaric, E}, title = {A comparison of alternative methods of measuring femoral anteversion.}, journal = {Journal of computer assisted tomography}, volume = {22}, number = {4}, pages = {610-614}, doi = {10.1097/00004728-199807000-00019}, pmid = {9676454}, issn = {0363-8715}, mesh = {Adult ; Aged ; Algorithms ; Arthritis, Rheumatoid/diagnostic imaging ; Computer Simulation ; Female ; Femur/*diagnostic imaging/pathology ; Femur Head Necrosis/diagnostic imaging ; Humans ; Male ; Middle Aged ; Models, Biological ; Tomography, X-Ray Computed/instrumentation/methods/statistics & numerical data ; }, abstract = {PURPOSE: Although CT scans are widely believed to provide the most accurate measurements of femoral anteversion, any estimate of the anteversion of the femur depends on the accuracy of the calculated axis of the femoral neck. We devised a method to measure the anteversion of the femur precisely using a 3D femoral computer model reconstructed from digitized femoral contours. Using this method, we compared the accuracy of three popular methods of anteversion measurement based on CT scans.

METHOD: The three popular CT methods were as follows: (a) the classic method of Weiner et al., based on a single CT image; (b) the method of Reikerås et al., in which the neck axis is defined by two superimposed images of the femoral head and neck; and (c) the method of Murphy et al., utilizing centroids of the head and the medullary canal. The accuracy of the single slice method was also examined using slices taken at four different neck slice levels within the proximal femur. CT scans of 30 femora were obtained using a helical CT scanner and reconstructed using custom software.

RESULTS: Based on the 3D model, the true anteversion of the femora averaged 19.8 +/- 9.3 degrees (SD). Using the method of Weiner et al., the anteversion of the femora was underestimated by an average of 6.4 degrees (predicted value 13.4 +/- 10.4 degrees). Conversely, Murphy et al.'s method overestimated anteversion by an average of 6.3 degrees with an average value of 26.0 +/- 9.1 degrees. The difference between the true anteversion and the values predicted by both of these methods was statistically significant (p < 0.001). The average anteversion measured according to the method of Reikerås et al. was 17.8 +/- 8.9 degrees, 2.0 degrees less than the true anteversion of the sample (p < 0.005). Anteversion angles predicted from a slice just below the inferior edge of the head averaged 18.3 +/- 9.5 degrees, only 1.5-3.1 degrees less than the true anteversion of the femur (p = 0.14).

CONCLUSION: The single slice CT method has sufficient accuracy for use, provided the slice is taken just below the femoral head. In cases with a femoral head deformity or a valgus neck or where difficulty is encountered in positioning the patient, 3D reconstruction appears essential for accurate measurement of anteversion.}, } @article {pmid9669100, year = {1998}, author = {Benedet, MJ and Christiansen, JA and Goodglass, H}, title = {A cross-linguistic study of grammatical morphology in Spanish- and English-speaking agrammatic patients.}, journal = {Cortex; a journal devoted to the study of the nervous system and behavior}, volume = {34}, number = {3}, pages = {309-336}, doi = {10.1016/s0010-9452(08)70758-5}, pmid = {9669100}, issn = {0010-9452}, mesh = {Adult ; Aged ; Aphasia, Broca/*diagnosis ; Aphasia, Wernicke/diagnosis ; Female ; Humans ; Male ; Middle Aged ; *Multilingualism ; *Neuropsychological Tests ; Phonetics ; Semantics ; Speech Production Measurement ; }, abstract = {To account for cross-linguistic differences in agrammatism, Bates and her colleagues have employed the Competition Model, proposing that the cue validity and cue costs of a grammatical morpheme in a particular language will directly affect how agrammatism is manifested. Using Goodglass et al.'s (1993) Morphosyntax Battery in English and a translated version in Spanish, we analyzed the use of equivalent grammatical structures in production and comprehension by agrammatic speakers of the two languages. Wilcoxon signed-rank tests revealed that the relative order of difficulty in both production and comprehension of various grammatical morphemes was the same for both Spanish- and English-speaking agrammatic patients, with two exceptions (1) the Spanish-speaking agrammatics were relatively better at producing subject-verb agreement, and (2) the Spanish speakers were significantly worse at comprehending both active and passive voice sentences. The Competition Model can explain the performance differences regarding subject-verb agreement and comprehension of active voice sentences, but it cannot account for the differences seen in comprehending passive voice sentences.}, } @article {pmid9650437, year = {1998}, author = {Brodeur, JB and Kurtz, RM and Strube, MJ}, title = {Hypnotic susceptibility order effects in waking analgesia.}, journal = {The International journal of clinical and experimental hypnosis}, volume = {46}, number = {3}, pages = {240-249}, doi = {10.1080/00207149808410005}, pmid = {9650437}, issn = {0020-7144}, mesh = {Adult ; Analgesia/*psychology ; Cross-Over Studies ; Female ; Humans ; *Hypnosis, Anesthetic ; Male ; Personality/*classification ; *Psychometrics/methods ; Research Design/*standards ; }, abstract = {This study reexamined Spanos, Hodgins, Stam, and Gwynn's (1984) contention that susceptibility testing order effects generated a relationship between waking analgesia pain reduction and level of hypnotic responsiveness. Undergraduate volunteers with no previous hypnosis experience were randomly assigned to two groups. Group 1 (n = 69) first received a cold pressor pain protocol, and then was administered the Standford Hypnotic Susceptibility Scale, Form C (SHSS:C). Group 2 (n = 69) was administered the SHSS:C prior to the cold pressor pain protocol. Our findings do not support Spanos, Hodgins et al.'s contention that susceptibility testing order effects generate the often reported relationship between waking analgesia and level of hypnotic responsiveness. We found significant partial correlation coefficients between the SHSS:C and nonhypnotic pain reduction regardless of order of susceptibility testing. Implications regarding the adequacy of design-generated expectancies to explain hypnotic analgesia phenomena were examined.}, } @article {pmid9638773, year = {1998}, author = {Smith, BL and Handley, P and Eldredge, DA}, title = {Sex differences in exercise motivation and body-image satisfaction among college students.}, journal = {Perceptual and motor skills}, volume = {86}, number = {2}, pages = {723-732}, doi = {10.2466/pms.1998.86.2.723}, pmid = {9638773}, issn = {0031-5125}, mesh = {Adolescent ; Adult ; *Body Image ; Body Weight ; Esthetics ; *Exercise ; Female ; Health Behavior ; Humans ; Male ; *Motivation ; *Personal Satisfaction ; Personality Inventory ; Social Behavior ; Students/*psychology ; Universities ; }, abstract = {The current study was an expansion of one by Cash, Novy, and Grant in 1994, in which responses of 101 female nursing students were examined for associations between reasons for exercise, frequency of exercise, and body-image satisfaction. In the current study, 78 male and 100 female undergraduates between the ages of 18 and 25 years (M = 21.2, SD = 1.9) from various majors completed a demographics/frequency of exercise survey, two body-assessment inventories, and the Reasons for Exercise Inventory of Silberstein, Striegel-Moore, Timko, and Rodin. Contrary to Cash, et al.'s findings, only health and fitness reasons were predictive of women's frequency of exercise, and women's dissatisfaction with specific bodily attributes was not significantly related to any reasons for exercising; however, like women in their sample, the current students who experienced more situational body dissatisfaction exercised for appearance and weight control. Sex comparisons indicated similar dissatisfaction with specific bodily attributes among men and women, but values were not significantly associated with any reasons for exercising. Women reported higher situational body dissatisfaction and exercising for appearance-related reasons more than men. Current participants may represent a more diverse group than previously tested, and the inventory's factor structure may not be generalizable to men and women.}, } @article {pmid9610116, year = {1998}, author = {Masters, MS}, title = {The gender difference on the Mental Rotations test is not due to performance factors.}, journal = {Memory & cognition}, volume = {26}, number = {3}, pages = {444-448}, pmid = {9610116}, issn = {0090-502X}, mesh = {Adolescent ; Adult ; *Attention ; Female ; *Gender Identity ; Humans ; *Imagination ; Male ; *Orientation ; *Pattern Recognition, Visual ; Psychophysics ; Reaction Time ; Reference Values ; }, abstract = {Men score higher than women on the Mental Rotations test (MRT), and the magnitude of this gender difference is the largest of that on any spatial test. Goldstein, Haldane, and Mitchell (1990) reported finding that the gender difference on the MRT disappears when "performance factors" are controlled--specifically, when subjects are allowed sufficient time to attempt all items on the test or when a scoring procedure that controls for the number of items attempted is used. The present experiment also explored whether eliminating these performance factors results in a disappearance of the gender difference on the test. Male and female college students were allowed a short time period or unlimited time on the MRT. The tests were scored according to three different procedures. The results showed no evidence that the gender difference on the MRT was affected by the scoring method or the time limit. Regardless of the scoring procedure, men scored higher than women, and the magnitude of the gender difference persisted undiminished when subjects completed all items on the test. Thus there was no evidence that performance factors produced the gender difference on the MRT. These results are consistent with the results of other investigators who have attempted to replicate Goldstein et al.'s findings.}, } @article {pmid9562899, year = {1998}, author = {Weinhardt, LS and Forsyth, AD and Carey, MP and Jaworski, BC and Durant, LE}, title = {Reliability and validity of self-report measures of HIV-related sexual behavior: progress since 1990 and recommendations for research and practice.}, journal = {Archives of sexual behavior}, volume = {27}, number = {2}, pages = {155-180}, pmid = {9562899}, issn = {0004-0002}, support = {K21 MH001101/MH/NIMH NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Female ; HIV Seropositivity/*psychology ; *Health Planning Guidelines ; Humans ; Male ; Middle Aged ; Reproducibility of Results ; Research ; Risk-Taking ; Sexual Behavior/*psychology ; *Surveys and Questionnaires ; }, abstract = {The trustworthiness of self-reported sexual behavior data has been questioned since Kinsey's pioneering surveys of sexuality in the United States (Kinsey et al., 1948, 1953). In the era of HIV and AIDS, researchers and practitioners have employed a diversity of assessment techniques but they have not escaped the fundamental problem of measurement error. We review the empirical literature produced since Catania et al.'s (1990) review regarding reliability and validity of self-administered and automated questionnaires, face-to-face interviews, telephone interviews, and self-monitoring approaches. We also provide specific recommendations for improving sexual behavior assessment. It is imperative that standardized self-report instruments be developed and used for sexual risk-behavior assessment.}, } @article {pmid9431731, year = {1997}, author = {Pratt, P and Tallis, F and Eysenck, M}, title = {Information-processing, storage characteristics and worry.}, journal = {Behaviour research and therapy}, volume = {35}, number = {11}, pages = {1015-1023}, doi = {10.1016/s0005-7967(97)00057-0}, pmid = {9431731}, issn = {0005-7967}, mesh = {Adolescent ; Adult ; Analysis of Variance ; Anxiety/*physiopathology ; *Association ; Case-Control Studies ; *Compulsive Behavior ; Cross-Sectional Studies ; Disease Susceptibility ; Female ; Humans ; Male ; Memory/*physiology ; Middle Aged ; }, abstract = {Eysenck (1984, Bulletin of the Psychonomic Society, 22, 545-548) suggested that storage characteristics may be an important determinant of worry, and postulated that prolonged worry occurs in individuals who have tightly organised clusters of worry-related information stored in long-term memory. These clusters reflect areas or domains of worry. Because the information is stored in tight clusters, it becomes more accessible, more rapidly activated and therefore retrieved more quickly. The Worry Domains Questionnaire (WDQ) (Tallis, 1991c) is used to determine which domain worried subjects most (Primary) and least (Secondary). Two experiments are reported using a word allocation task, which requires subjects to make categorical decisions, based on these worry domains. It is reported that priming facilitates the emergence of domain effects, thus providing support for a structural hypothesis. High worries take longer to reject negative words if they are from the Primary domain and have difficulty rejecting Primary domain words when they are under a congruent heading. In addition, high worriers are reported to show retarded latencies when attempting to process ambiguous information, consistent with Metzger et al.'s studies (1990, Journal of Clinical Psychology, 48, 76-88). It is suggested that the initiation and maintenance of worry is largely attributable to an elevated evidence requirement and this may link to the personality trait of perfectionism.}, } @article {pmid9425878, year = {1997}, author = {Kastner, TA}, title = {Cost-effectiveness of evaluating the new technologies.}, journal = {Mental retardation}, volume = {35}, number = {6}, pages = {475-476}, doi = {10.1352/0047-6765(1997)035<0475:COETNT>2.0.CO;2}, pmid = {9425878}, issn = {0047-6765}, mesh = {Cost-Benefit Analysis ; Drugs, Generic/*economics ; Humans ; }, abstract = {The problem of evaluating cost-effectiveness claims is complex and not readily solved. However, such evaluation represents an important direction for technology assessment as resources become more scarce. Neumann et al.'s analysis (1996) represents one solution to the relatively simple problem of pharmacoeconomic studies. In addition, Fryback and Thornbury included a useful method for approaching the cost-effectiveness of all medical technologies. I note that the cost-effectiveness cutoff of $50,000 per quality-adjusted life year is an incremental one, meaning that new technology must be substantially more cost-effective than older technology. This is currently not the case where incremental improvements over previous technology are often quite small. Interested readers are referred to standard tests in the field, including Drummond, Stoddart, and Torrance (1987), Eisenberg (1986), and Sox, Blatt, Higgins, and Marton (1988).}, } @article {pmid9348823, year = {1997}, author = {Bennett, K and Stevens, R}, title = {The internal structure of the Eating Disorder Inventory.}, journal = {Health care for women international}, volume = {18}, number = {5}, pages = {495-504}, doi = {10.1080/07399339709516303}, pmid = {9348823}, issn = {0739-9332}, mesh = {Adolescent ; Adult ; Aged ; Analysis of Variance ; Factor Analysis, Statistical ; Feeding and Eating Disorders/*diagnosis/*psychology ; Female ; Humans ; Middle Aged ; Personality Inventory/*standards ; Psychometrics ; }, abstract = {The Eating Disorder Inventory (EDI; Garner, Olmsted, & Polivy, 1983) is used as a screening instrument for identifying potential anorexia nervosa and bulimia nervosa. It comprises eight subscales: Bulimia, Drive for Thinness, Body Dissatisfaction, Maturity Fears, Introceptive Awareness, Perfectionism, Interpersonal Distrust, and Ineffectiveness. We examined the internal structure of the EDI using a principle components factor analysis, for a sample of women with no known eating disorder. The results of the factor analyses showed differences between the extracted factors and Garner et al.'s subscales. Seven factors were extracted, accounting for 60.8% of the variance. The first factor accounted for 33.5% of the variance. The analysis indicated that items factored along positive-negative and factual-emotional lines. We conclude that at present there is not enough evidence to support the efficacy of the subscale structure with women who are not known to have eating disorders.}, } @article {pmid9392898, year = {1997}, author = {Adams, SH and John, OP}, title = {A hostility scale for the California Psychological Inventory: MMPI, observer Q-sort, and big-five correlates.}, journal = {Journal of personality assessment}, volume = {69}, number = {2}, pages = {408-424}, doi = {10.1207/s15327752jpa6902_11}, pmid = {9392898}, issn = {0022-3891}, support = {MH43948/MH/NIMH NIH HHS/United States ; T32 HL07365-16/HL/NHLBI NIH HHS/United States ; T32 MH19391/MH/NIMH NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Female ; Humans ; Longitudinal Studies ; MMPI/*statistics & numerical data ; Male ; Observer Variation ; Personality Assessment/*statistics & numerical data ; Personality Inventory/*statistics & numerical data ; Psychometrics ; Q-Sort/*statistics & numerical data ; Reproducibility of Results ; Students/psychology ; }, abstract = {Using two samples, we developed and validated a hostility scale that can be scored from the California Psychological Inventory (CPI) and serves as an alternate for the Cook-Medley Hostility Scale (Ho; Cook & Medley, 1954). The CPI Hostility (H) scale consists of 33 items that are either duplicates or close equivalents of specific Ho items, and the two scales correlate at least .90 in samples differing in sex. The H and Ho scales show a similar pattern of correlations with conceptually relevant MMPI scales and with observer-rated personality attributes tapping Barefoot, Peterson, et al.'s (1991) five hostility categories of Hostile Affect, Cynicism, Aggressive Responding, Social Avoidance, and Hostile Attributions. These findings provide evidence for the equivalence of the two hostility scales, as well as external validation for those personality characteristics that are purported to underlie the construct of hostility as tapped by both the original Ho scale and the new CPI H scale.}, } @article {pmid9364757, year = {1997}, author = {Kruglanski, AW and Atash, MN and DeGrada, E and Mannetti, L and Pierro, A and Webster, DM}, title = {Psychological theory testing versus psychometric nay-saying: comment on Neuberg et al.'s (1997) critique of the need for closure scale.}, journal = {Journal of personality and social psychology}, volume = {73}, number = {5}, pages = {1005-16; discussion 1017-29}, doi = {10.1037//0022-3514.73.5.1005}, pmid = {9364757}, issn = {0022-3514}, support = {1R01 MH52578/MH/NIMH NIH HHS/United States ; K057MH01213/MH/NIMH NIH HHS/United States ; }, mesh = {Humans ; Individuality ; Personality Inventory/*statistics & numerical data ; *Psychological Theory ; Psychometrics ; Reproducibility of Results ; *Social Perception ; }, abstract = {S. L. Neuberg, T. N. Judice, and S. G. West (1997) faulted our work with the Need for Closure Scale (NFCS) on grounds that the NFCS lacks discriminant validity relative to S. L. Neuberg's and J. T. Newsom's (1993) Personal Need for Structure (PNS) Scale and is multidimensional, which, so they claim, renders the use of its total score inadmissible. By contrast, the present authors show that neither of the above assertions is incompatible with the underlying need for closure theory. Relations between NFCS and the PNS are to be expected, as these were designed to operationalize the very same construct (of need for closure). Furthermore, no unidimensionality of the NFCS has been claimed, and none is required to use its total score for testing various theoretically derived predictions. An instrument's ultimate utility hinges on theoretical considerations and empirical evidence rather than on questionable psychometric dogma unrelated to the substantive matters at hand.}, } @article {pmid9364632, year = {1997}, author = {Landuyt, W and Fowler, J and Ruifrok, A and Stüben, G and van der Kogel, A and van der Schueren, E}, title = {Kinetics of repair in the spinal cord of the rat.}, journal = {Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology}, volume = {45}, number = {1}, pages = {55-62}, doi = {10.1016/s0167-8140(97)00139-4}, pmid = {9364632}, issn = {0167-8140}, mesh = {Animals ; Brachytherapy/methods ; Confidence Intervals ; Dose-Response Relationship, Radiation ; Kinetics ; Male ; Radiation Dosage ; *Radiation Injuries, Experimental ; Rats ; Spinal Cord/pathology/*radiation effects ; Spinal Cord Diseases/etiology/*prevention & control ; *Wound Healing ; }, abstract = {PURPOSE: Split dose experiments were carried out with two 2 Gy fractions per day at intervals ranging from 0.5 to 24 h, in order to investigate both the time to complete repair and the detailed kinetics of repair of sublethal damage in the cervical spine of rats.

MATERIALS AND METHODS: Male rats of the WAG/Rij strain were irradiated at 2 Gy/min with 18 MV photons to a length of 18 mm of cervical spinal cord. Four hundred twenty-three rats were irradiated without top-up doses to investigate whether repair was complete by 24 h or whether any slow repair or proliferation occurred up to 50 days after irradiation. Three hundred seventy-nine rats were also irradiated in split dose (2 Gy + delta t + 2 Gy each day) experiments, with intervals of 0.5, 1, 2, 4, 8 and 24 h. The split dose irradiations were followed by a single top-up dose of 15 Gy (producing about half the total damage).

RESULTS: Repair was complete by 24 h as the ED50 values were the same at 1, 11 and 50 day intervals for two large fractions, and for 10 fractions in 10 or 50 days. A mono-exponential component of repair of T1/2 = 0.25 (95% CI 0.16-0.48) h was determined by direct analysis using all the data and T1/2 = 0.37 (0.28-0.53) h for the split 2 Gy doses with top-up only. A bi-exponential analysis did not fit better. The presence of a second component was demonstrated graphically, with T1/2 of about 6.5 h but with a wide confidence interval from near 0 to 13 h. However, the 24 h ED50 was significantly different from all ED50s except the 8 h value. Considering all data together, an upper limit of about 7 h could be placed on any long component, or else repair could not be complete by 24 h.

DISCUSSION AND CONCLUSIONS: Two components of repair (0.7 and 3.8 h) have been reported by Ang et al. (Ang, K.K., Jiang, G.L., Guttenberger, R., Thames, H.D., Stephens, L.C., Smith, C.D. and Feng, Y. Impact of spinal cord repair kinetics on the practice of altered fractionation schedules. Radiother. Oncol. 25: 287-294, 1992) in the spinal cord of Sprague-Dawley rats. Two components have also been reported by others more recently. The present results could, with its graphical interpretation, agree in principle, but with a shorter fast component and a longer slow component. A slow component of 5.5 h was reported by Ruifrok et al. (Ruifrok, A.C.C., Kleiboer, B.J. and van der Kogel, A.J. Fractionation sensitivity of rat cervical spinal cord during radiation retreatment. Radiother. Oncol. 25: 295-300, 1992) in a related strain of WAG/Rij rats. The possible presence of a slower component than Ang et al.'s 3.8 h might help to explain the four myelopathies observed in the pilot studies for the CHART clinical trial. The presence of the definite fast component (< 0.5 h) could have important consequences when pulsed brachytherapy is used to replace continuous low dose rate irradiation.}, } @article {pmid9331456, year = {1997}, author = {Hamrick, MW}, title = {Functional osteology of the primate carpus with special reference to strepsirhini.}, journal = {American journal of physical anthropology}, volume = {104}, number = {1}, pages = {105-116}, doi = {10.1002/(SICI)1096-8644(199709)104:1<105::AID-AJPA7>3.0.CO;2-Q}, pmid = {9331456}, issn = {0002-9483}, mesh = {Animals ; Anthropometry ; Biological Evolution ; Biomechanical Phenomena ; Carpus, Animal/*anatomy & histology ; Fossils ; Haplorhini/*anatomy & histology ; Locomotion ; Strepsirhini/*anatomy & histology ; }, abstract = {Preuschoft et al. ([1993] in H. Preuschoft and D. Chivers (eds): Hands of Primates. New York: Springer-Verlag, pp. 245-256) used a theoretical biomechanical analysis to generate several predictions relating subordinal differences in primate hand proportions to differences in carpal morphology. This study tests these predictions using quantitative analyses of carpal morphology between extant haplorhine and strepsirhine primates. Results show that living strepsirhines have a significantly larger hamate hamulus than do haplorhines, supporting a Preuschoft et al.'s (1993) predictions. Extant strepsirhines also have a significantly shorter pisiform body than do haplorhines and arboreal nonprimate eutherians and a larger scaphoid tubercle than new and Old World monkeys. These results contrast markedly with those expected under Preuschoft et al.'s (1993) model. Furthermore, strepsirhines and haplorhines do not differ significantly in the relative size of their radiocarpal articulations. These morphometric observations do not match the predicted morphological patterns because the kinematic assumptions upon which the biomechanical models are based are incorrect. Living strepsirhines appear to be derived in having very deep radial and ulnar margins of the carpal tunnel for well-developed extrinsic digital flexors. Moreover, tooth-combed prosimians differ from most haplorhines, early Tertiary adapiforms, and arboreal nonprimate eutherians in having a relatively short pisiform body, which gives the flexor carpi ulnaris less power to flex the wrist from extended (= dorsiflexed) positions. These structural observations suggest that powerful manual grasping and an emphasis on leaping and climbing, rather than palmigrade quadrupedal walking and running, are morphotypic for extant Strepsirhini.}, } @article {pmid9254924, year = {1997}, author = {Gu, X}, title = {The age of the common ancestor of eukaryotes and prokaryotes: statistical inferences.}, journal = {Molecular biology and evolution}, volume = {14}, number = {8}, pages = {861-866}, doi = {10.1093/oxfordjournals.molbev.a025827}, pmid = {9254924}, issn = {0737-4038}, mesh = {Amino Acid Sequence ; *Eukaryotic Cells ; *Evolution, Molecular ; Fossils ; *Prokaryotic Cells ; Sequence Alignment ; Sequence Homology, Amino Acid ; Statistics as Topic ; Time Factors ; }, abstract = {In this paper, a simple distance measure was used to estimate the age (T) of the common ancestor of eukaryotes and prokaryotes which takes the rate variation among sites and the pattern of amino acid substitutions into account. Our new estimate of T based on Doolittle et al.'s data is about 2.5 billion years ago (Ga), with 95% confidence interval from 2.1 to 2.9 Ga. This result indicates (1) that Doolittle et al.'s estimate (approximately 2.0 Ga) seems too recent, and (2) that the traditional view about the divergence time between eukaryotes and prokaryotes (T0 = 3.5 Ga) can be rejected at the 0.1% significance level.}, } @article {pmid9241953, year = {1997}, author = {Kwapil, TR and Miller, MB and Zinser, MC and Chapman, J and Chapman, LJ}, title = {Magical ideation and social anhedonia as predictors of psychosis proneness: a partial replication.}, journal = {Journal of abnormal psychology}, volume = {106}, number = {3}, pages = {491-495}, doi = {10.1037//0021-843x.106.3.491}, pmid = {9241953}, issn = {0021-843X}, mesh = {Adult ; Affective Symptoms/diagnosis/psychology ; Disease Susceptibility ; Female ; Follow-Up Studies ; Humans ; Interpersonal Relations ; Male ; Psychiatric Status Rating Scales/*statistics & numerical data ; Psychotic Disorders/*diagnosis/psychology ; Severity of Illness Index ; }, abstract = {The authors compared college students identified by high scores on the Magical Ideation Scale (M. Eckblad & L. J. Chapman, 1983) and the Revised Social Anhedonia Scale (MagSoc; n = 28; M. Eckblad, L. J. Chapman, J. P. Chapman, & M. Mishlove, 1982) with control participants (n = 20) at a 10-year follow-up assessment in an attempt to replicate L. J. Chapman, J. P. Chapman, T. R. Kwapil, M. Eckblad, and M. C. Zinser's (1994) report of heightened psychosis proneness in MagSoc individuals. The MagSoc group exceeded the control group on severity of psychotic-like experiences; ratings of schizotypal, paranoid, and borderline personality disorder symptoms; and rates of mood and substance use disorders. Two of the MagSoc participants but none of the control participants developed psychosis during the follow-up period (a nonsignificant difference). Consistent with L. J. Chapman et al.'s findings, the groups did not differ on rates of personality disorders or relatives with psychosis.}, } @article {pmid12292413, year = {1997}, author = {}, title = {Controversial report warns of recycled glove use in Kenyan hospital.}, journal = {AIDS weekly plus}, volume = {}, number = {}, pages = {19-20}, pmid = {12292413}, mesh = {Africa ; Africa South of the Sahara ; Africa, Eastern ; Developing Countries ; Disease ; *Equipment and Supplies ; Health ; *Infections ; Kenya ; Public Health ; *Safety ; }, } @article {pmid9586497, year = {1997}, author = {Flatau, A}, title = {Flatau challenges Dunn, et al.'s priority claim to the discovery of the sphenomandibularis muscle.}, journal = {Cranio : the journal of craniomandibular practice}, volume = {15}, number = {3}, pages = {189-192}, pmid = {9586497}, issn = {0886-9634}, mesh = {Temporal Muscle/*anatomy & histology ; }, } @article {pmid9186376, year = {1997}, author = {Molineaux, L}, title = {Nature's experiment: what implications for malaria prevention?.}, journal = {Lancet (London, England)}, volume = {349}, number = {9066}, pages = {1636-1637}, doi = {10.1016/S0140-6736(97)22023-4}, pmid = {9186376}, issn = {0140-6736}, mesh = {Africa/epidemiology ; Child ; Child, Preschool ; Hospitalization/statistics & numerical data ; Humans ; Infant ; Infant, Newborn ; Malaria, Falciparum/*epidemiology/immunology/prevention & control/transmission ; }, } @article {pmid12158999, year = {1997}, author = {James, WH}, title = {The validity of inferences of sex-selective infanticide, abortion and neglect from unusual reported sex ratios at birth.}, journal = {European journal of population = Revue europeenne de demographie}, volume = {13}, number = {2}, pages = {213-217}, pmid = {12158999}, issn = {0168-6577}, mesh = {*Abortion, Induced ; Africa ; Africa South of the Sahara ; Africa, Eastern ; Behavior ; Crime ; Data Collection ; Demography ; Developing Countries ; *Evaluation Studies as Topic ; Family Characteristics ; Family Planning Services ; Family Relations ; *Infanticide ; *Nuclear Family ; Population ; Population Characteristics ; Psychology ; *Reproducibility of Results ; Research ; *Research Design ; *Sex ; Sex Distribution ; Sex Factors ; *Sex Ratio ; Social Problems ; Social Values ; Zambia ; }, } @article {pmid9251600, year = {1997}, author = {Cunha, Mda G and Schettini, AP and Pereira, ES and Pedrosa, VL and Cruz, RC and Sadahiro, M}, title = {Regarding Brasil, et al.'s adverse effects in leprosy's WHO/MDT and paramedic's role in leprosy control program.}, journal = {International journal of leprosy and other mycobacterial diseases : official organ of the International Leprosy Association}, volume = {65}, number = {2}, pages = {257-259}, pmid = {9251600}, issn = {0148-916X}, mesh = {Acute Kidney Injury/chemically induced/etiology ; *Allied Health Personnel ; Anti-Infective Agents/*adverse effects/therapeutic use ; Brazil/epidemiology ; Communicable Disease Control ; Drug Therapy, Combination ; Humans ; Leprostatic Agents/*adverse effects/therapeutic use ; Leprosy/*drug therapy/epidemiology/prevention & control ; World Health Organization ; }, } @article {pmid9229473, year = {1997}, author = {Lange, R and Houran, J}, title = {Context-induced paranormal experiences: support for Houran and Lange's model of haunting phenomena.}, journal = {Perceptual and motor skills}, volume = {84}, number = {3 Pt 2}, pages = {1455-1458}, doi = {10.2466/pms.1997.84.3c.1455}, pmid = {9229473}, issn = {0031-5125}, mesh = {Adult ; Humans ; *Models, Psychological ; *Parapsychology ; Perception ; Random Allocation ; Research Design ; *Suggestion ; Surveys and Questionnaires ; }, abstract = {Houran and Lange's psychological model of haunting phenomena predicts that contextual variables alone are sufficient to induce poltergeist-like perceptions. 22 subjects individually visited five areas of a performance theater and were asked to notice the environment. 11 subjects in an informed condition were instructed that the location was haunted, while 11 in the control condition were told that the building was simply under renovation. Subjects' perceptions in both conditions were recorded via Green, et al.'s 1992 experiential questionnaire which contains 10 subscales related to psychological and physiological perceptions. Analysis yielded significantly more intense perceptual experiences on nine of the ten subscales in the informed condition, indicating that demand characteristics alone can stimulate paranormal-type experiences.}, } @article {pmid9191814, year = {1997}, author = {Chambless, LE and Hosking, JD and Kronmal, R and Howard, G and Howard, VJ and Toole, JF}, title = {Clearing up misunderstandings about clinical trial methodology: a reply to Barnett et al.'s commentary on the ACAS Trial. ACAS Executive Committee, ACAS Data and Safety Monitoring Committee.}, journal = {Neurology}, volume = {48}, number = {6}, pages = {1743-5; author reply 1745-8}, doi = {10.1212/wnl.48.6.1743}, pmid = {9191814}, issn = {0028-3878}, mesh = {Clinical Trials as Topic/*methods ; *Endarterectomy, Carotid ; Humans ; }, } @article {pmid9172219, year = {1997}, author = {Greenberg, AC}, title = {Comment regarding Malik, et al.'s (1996) "The method of subliminal psychodynamic activation: do individual thresholds make a difference?".}, journal = {Perceptual and motor skills}, volume = {84}, number = {3 Pt 1}, pages = {1024-1026}, doi = {10.2466/pms.1997.84.3.1024}, pmid = {9172219}, issn = {0031-5125}, mesh = {*Arousal ; Heart Rate ; Humans ; *Individuality ; Object Attachment ; Problem Solving ; *Psychoanalytic Theory ; Sensory Thresholds ; *Subliminal Stimulation ; }, abstract = {Researchers using the method of subliminal psychodynamic activation need to consider the neutrality of their control messages. Anagrams or numbers are recommended as even benign-sounding phrases can produce nonneutral effects.}, } @article {pmid9149921, year = {1997}, author = {Mix, KS and Levine, SC and Huttenlocher, J}, title = {Numerical abstraction in infants: another look.}, journal = {Developmental psychology}, volume = {33}, number = {3}, pages = {423-428}, doi = {10.1037//0012-1649.33.3.423}, pmid = {9149921}, issn = {0012-1649}, mesh = {*Attention ; Auditory Perception ; Discrimination Learning ; Female ; Humans ; Infant ; Male ; Pattern Recognition, Visual ; *Problem Solving ; *Psychology, Child ; }, abstract = {This article examines an important finding from the literature on infant numerical competence. The finding, reported by P. Starkey, E. S. Spelke, and R. Gelman (1990), was that infants looked longer toward a visual display that was equal in number to an auditory set. In Experiment 1, when the procedures described by P. Starkey et al. were followed and duration was held constant across auditory sequences that varied in number, infants looked longer toward the display that was not numerically equivalent to the auditory set. In Experiment 2, when the rate and duration of the auditory sequences were varied randomly within infants, no significant preference for either the equivalent or nonequivalent visual display was shown. These results raise questions about P. Starkey et al.'s claims that infants can represent the numerosity of sets in different modalities and then perform one-one correspondence computations over them.}, } @article {pmid9103995, year = {1997}, author = {Powell, S and Nelson, B}, title = {Effects of choosing academic assignments on a student with attention deficit hyperactivity disorder.}, journal = {Journal of applied behavior analysis}, volume = {30}, number = {1}, pages = {181-183}, pmid = {9103995}, issn = {0021-8855}, mesh = {Attention ; Attention Deficit Disorder with Hyperactivity/psychology/*therapy ; *Behavior Therapy ; Child ; *Choice Behavior ; Cooperative Behavior ; Humans ; Internal-External Control ; Male ; *Motivation ; }, abstract = {The effects of choosing academic assignments on the undesirable behaviors manifested by a second-grade student with attention deficit hyperactivity disorder were analyzed. This study extended Dunlap et al.'s (1994) research on choice making as a form of antecedent control. A reversal design showed that undesirable behaviors decreased when the student was given a choice of academic assignments.}, } @article {pmid9095541, year = {1997}, author = {Martin, GM and Harley, CW and Smith, AR and Hoyles, ES and Hynes, CA}, title = {Spatial disorientation blocks reliable goal location on a plus maze but does not prevent goal location in the Morris maze.}, journal = {Journal of experimental psychology. Animal behavior processes}, volume = {23}, number = {2}, pages = {183-193}, doi = {10.1037//0097-7403.23.2.183}, pmid = {9095541}, issn = {0097-7403}, mesh = {Animals ; Cues ; *Escape Reaction ; Male ; *Maze Learning ; Mental Recall ; *Orientation ; *Problem Solving ; Rats ; Sensory Deprivation ; Social Environment ; *Space Perception ; }, abstract = {Cue control in spatial learning was investigated in a plus maze and a Morris maze. Rats transported in opaque containers with prior rotation to a plus maze, but not a Morris maze, could not find a goal defined by external cues. Rats transported in clear containers without rotation found the goal in both mazes. In the Morris maze, goal location was readily relearned following cue removal by rats in clear containers but not by rats in the opaque/rotation group. B. L. McNaughton et al.'s (1996) theory that during spatial learning sensory information is bound to preconfigured internal maps in the hippocampus, whose metric is self-motion and whose orientation depends on input from an inertial based head direction system, may explain this study's findings.}, } @article {pmid9075005, year = {1997}, author = {Wu, JZ and Herzog, W and Epstein, M}, title = {An improved solution for the contact of two biphasic cartilage layers.}, journal = {Journal of biomechanics}, volume = {30}, number = {4}, pages = {371-375}, doi = {10.1016/s0021-9290(96)00148-0}, pmid = {9075005}, issn = {0021-9290}, mesh = {Biomechanical Phenomena ; Cartilage, Articular/*physiology ; Humans ; *Models, Biological ; }, abstract = {The purpose of this study was to present a solution for the contact of two biphasic cartilage layers which can be used for dynamic loading, is not restricted to predictions over small time periods, and predicts biologically meaningful changes in contact areas over time. The proposed solution was based on the work of Ateshian et al. (1994, J. Biomechanics 27, 1347-1360) who retained the first term of an asymptotic expansion and used an approximate integration which is valid for short time periods. The solution proposed here uses an exact integration, is valid over long time periods, and can be used for increasing loading. The new solution corrects a limitation of the work by Ateshian et al., which manifests itself immediately (i.e. at time t = 0+ s): the rate of change in the contact radius (and therefore, the contact area) is increasing in Ateshian et al.'s solution for a constant force, whereas it is decreasing in the new solution. An increasing rate of change in the contact radius suggests that the contact radius (area) is unbounded, and a steady-state solution cannot be reached, which is physically not correct for the contact of two joint surfaces. In the new solution, the contact radius reaches a steady-state value given sufficient time.}, } @article {pmid9207763, year = {1997}, author = {Wendl-Richter, HU}, title = {Regarding Pinitsoontorn, et al.'s rapid village survey.}, journal = {International journal of leprosy and other mycobacterial diseases : official organ of the International Leprosy Association}, volume = {65}, number = {1}, pages = {102-103}, pmid = {9207763}, issn = {0148-916X}, mesh = {Humans ; Leprosy/*epidemiology ; Population Surveillance/*methods ; Public Health Administration/methods ; Thailand/epidemiology ; }, } @article {pmid9207761, year = {1997}, author = {Frankel, RI}, title = {Regarding Ebenezer, et al.'s MB nerve histology in clinically diagnosed BT leprosy patients.}, journal = {International journal of leprosy and other mycobacterial diseases : official organ of the International Leprosy Association}, volume = {65}, number = {1}, pages = {99-100}, pmid = {9207761}, issn = {0148-916X}, mesh = {Humans ; Leprosy, Borderline/*classification/diagnosis ; Leprosy, Tuberculoid/*classification/diagnosis ; Skin/microbiology/pathology ; World Health Organization ; }, } @article {pmid9185287, year = {1997}, author = {Meng, XL}, title = {The EM algorithm and medical studies: a historical link.}, journal = {Statistical methods in medical research}, volume = {6}, number = {1}, pages = {3-23}, doi = {10.1177/096228029700600102}, pmid = {9185287}, issn = {0962-2802}, mesh = {*Algorithms ; Analysis of Variance ; Biometry/*history/methods ; Confidence Intervals ; Disease Outbreaks/history/statistics & numerical data ; History, 20th Century ; Humans ; Likelihood Functions ; Poisson Distribution ; United Kingdom ; }, abstract = {Anderson Gray McKendrick's 1926 paper, 'Applications of mathematics to medical problems', was the earliest reference cited in Dempster et al.'s 1977 paper that defined and popularized the EM algorithm. McKendrick's paper was prominently featured by Joseph Oscar Irwin in his 1962 inaugural address as the President of the Royal Statistical Society (in the UK), entitled 'The place of mathematics in medical and biological statistics'. The link of McKendrick's work to the EM algorithm is due to an improvement made by Irwin on a novel method McKendrick used for estimating an infection rate when the observed data do not distinguish between those individuals who are not susceptible to the infection and those who are susceptible, but do not develop symptoms. This article examines this link, along the way illustrating the central ideas underlying the EM algorithm as well as its properties; the examination also suggests a profiling strategy for speeding up EM, which may be worthy of general investigation. McKendrick's data on an epidemic of cholera are used for illustration and to compare EM with Irwin's method as well as the Newton-Raphson algorithm. Issues beyond computation are also discussed whenever appropriate.}, } @article {pmid9152714, year = {1997}, author = {Graham, C and Ballard, C and Saad, K}, title = {Variables which distinguish patients fulfilling clinical criteria for dementia with Lewy bodies from those with Alzheimer's disease.}, journal = {International journal of geriatric psychiatry}, volume = {12}, number = {3}, pages = {314-318}, pmid = {9152714}, issn = {0885-6230}, mesh = {Aged ; Aged, 80 and over ; Alzheimer Disease/classification/*diagnosis/psychology ; Cohort Studies ; Dementia/classification/*diagnosis/psychology ; Diagnosis, Differential ; Female ; Geriatric Assessment ; Humans ; Male ; Neurologic Examination ; Neuropsychological Tests ; Parkinson Disease/classification/*diagnosis/psychology ; Prospective Studies ; Psychiatric Status Rating Scales ; }, abstract = {OBJECTIVES: To compare patients fulfilling clinical criteria for Lewy body dementia with those meeting clinical criteria for Alzheimer's disease.

DESIGN: Prospective cohort study.

SETTING: Psychiatric services and a memory clinic.

SAMPLE: 124 patients with DSM-III-R dementia.

MEASURES: The assessment included the GMS/HAS/SDS package, the CAMCOG, the Cornell Depression scale and the Burns Symptom Checklist. Dementia was diagnosed according to DSM-III-R, NINCDS ADRDA, McKeith, Byrne, Hachinski and HAS AGECAT criteria.

RESULTS: Patients meeting McKeith et al. criteria for senile dementia of Lewy body type were significantly more likely to have clouding of consciousness, significant Parkinsonian symptoms and less severely impaired recent memory than patients with NINCDS ADRDA Alzheimer's disease. Each of these variables also distinguished patients meeting Byrne et al.'s criteria for dementia with Lewy bodies from those with a diagnosis of Alzheimer's disease.

CONCLUSIONS: It is suggested that one set of criteria could encompass those overlapping groups of patients. Work is needed to further develop the diagnostic criteria for Lewy body dementia.}, } @article {pmid9147602, year = {1997}, author = {Song, HH}, title = {Analysis of correlated ROC areas in diagnostic testing.}, journal = {Biometrics}, volume = {53}, number = {1}, pages = {370-382}, pmid = {9147602}, issn = {0006-341X}, mesh = {Analysis of Variance ; Biometry ; Computer Simulation ; Diagnostic Tests, Routine/*statistics & numerical data ; Humans ; Monte Carlo Method ; *ROC Curve ; Radiology/statistics & numerical data ; }, abstract = {This paper focuses on methods of analysis of areas under receiver operating characteristic (ROC) curves. Analysis of ROC areas should incorporate the correlation structure of repeated measurements taken on the same set of cases and the paucity of measurements per treatment resulting from an effective summarization of cases into a few area measures of diagnostic accuracy. The repeated nature of ROC data has been taken into consideration in the analysis methods previously suggested by Swets and Pickett (1982, Evaluation of Diagnostic Systems: Methods from Signal Detection Theory), Hanley and McNeil (1983, Radiology 148, 839-843), and DeLong, DeLong, and Clarke-Pearson (1988, Biometrics 44, 837-845). DeLong et al.'s procedure is extended to a Wald test for general situations of diagnostic testing. The method of analyzing jackknife pseudovalues by treating them as data is extremely useful when the number of area measures to be tested is quite small. The Wald test based on covariances of multivariate multisample U-statistics is compared with two approaches of analyzing pseudovalues, the univariate mixed-model analysis of variance (ANOVA) for repeated measurements and the three-way factorial ANOVA. Monte Carlo simulations demonstrate that the three tests give good approximation to the nominal size at the 5% levels for large sample sizes, but the paired t-test using ROC areas as data lacks the power of the other three tests and Hanley and McNeil's method is inappropriate for testing diagnostic accuracies. The Wald statistic performs better than the ANOVAs of pseudovalues. Jackknifing schemes of multiple deletion where different structures of normal and diseased distributions are accounted for appear to perform slightly better than simple multiple-deletion schemes but no appreciable power difference is apparent, and deletion of too many cases at a time may sacrifice power. These methods have important applications in diagnostic testing in ROC studies of radiology and of medicine in general.}, } @article {pmid9090143, year = {1997}, author = {Cohen, JD and Dunbar, KO and Barch, DM and Braver, TS}, title = {Issues concerning relative speed of processing hypotheses, schizophrenic performance deficits, and prefrontal function: comment on Schooler et al. (1997).}, journal = {Journal of experimental psychology. General}, volume = {126}, number = {1}, pages = {37-41}, doi = {10.1037//0096-3445.126.1.37}, pmid = {9090143}, issn = {0096-3445}, mesh = {*Attention ; *Color Perception ; Humans ; Prefrontal Cortex/*physiopathology ; Reaction Time ; Schizophrenia/diagnosis/*physiopathology ; Schizophrenic Psychology ; Verbal Behavior ; }, abstract = {The authors have found the data presented in the C. Schooler, E. Neumann, L. J. Caplan, and B. R. Roberts (1997) article to be interesting and of potential value in constraining the further development of detailed theoretical models of Stroop performance. However, the authors have found that the relative speed of processing account of stimulus onset asynchrony (SOA) effects given by Schooler et al. in Experiment 1 fails to address several important and vexing issues faced by such accounts, which have been highlighted by existing formal models. The authors also have expressed concerns about Schooler et al.'s, interpretation of the reduction in Stroop interference observed among individuals with schizophrenia in Experiment 2. Whereas the authors have acknowledged that it is plausible to relate this to a dysfunction of prefrontal cortex, they have pointed to equally plausible alternative explanations, which are not addressed by the experiment or in the discussion in the Schooler et al. article.}, } @article {pmid9141906, year = {1997}, author = {Imai, M and Gentner, D}, title = {A cross-linguistic study of early word meaning: universal ontology and linguistic influence.}, journal = {Cognition}, volume = {62}, number = {2}, pages = {169-200}, doi = {10.1016/s0010-0277(96)00784-6}, pmid = {9141906}, issn = {0010-0277}, mesh = {Adult ; Child, Preschool ; *Cross-Cultural Comparison ; Female ; Humans ; Japan ; *Language ; *Language Development ; Male ; Pattern Recognition, Visual ; Psycholinguistics ; United States ; *Verbal Learning ; }, abstract = {This research concerns how children learn the distinction between substance names and object names. Quine (1969) proposed that children learn the distinction through learning the syntactic distinctions inherent in count/mass grammar. However, Soja et al. (1991) found that English-speaking 2-year-olds, who did not seem to have acquired count/mass grammar, distinguished objects from substances in a word extension task, suggesting a pre-linguistic ontological distinction. To test whether the distinction between object names and substance names is conceptually or linguistically driven, we repeated Soja et al.'s study with English- and Japanese-speaking 2-, 2.5-, and 4-year-olds and adults. Japanese does not make a count-mass grammatical distinction: all inanimate nouns are treated alike. Thus if young Japanese children made the object-substance distinction in word meaning, this would support the early ontology position over the linguistic influence position. We used three types of standards: substances (e.g., sand in an S-shape), simple objects (e.g., a kidney-shaped piece of paraffin) and complex objects (e.g., a wood whisk). The subjects learned novel nouns in neutral syntax denoting each standard entity. They were then asked which of the two alternatives--one matching in shape but not material and the other matching in material but not shape--would also be named by the same label. The results suggest the universal use of ontological knowledge in early word learning. Children in both languages showed differentiation between (complex) objects and substances as early as 2 years of age. However, there were also early cross-linguistic differences. American and Japanese children generalized the simple object instances and the substance instances differently. We speculate that children universally make a distinction between individuals and non-individuals in word learning but that the nature of the categories and the boundary between them is influenced by language.}, } @article {pmid9645232, year = {1997}, author = {Charlemaine, C and Duyme, M and Aubin, JT and Guis, F and Marquiset, N and de Pirieux, I and Strub, N and Brossard, Y and Jarry, G and Frydman, R and Pons, JC}, title = {Twin zygosity diagnosis by mailed questionnaire below age twelve months. Le Groupe Romulus.}, journal = {Acta geneticae medicae et gemellologiae}, volume = {46}, number = {3}, pages = {147-156}, doi = {10.1017/s0001566000000568}, pmid = {9645232}, issn = {0001-5660}, mesh = {Humans ; Infant ; Postal Service ; Surveys and Questionnaires ; *Twins, Dizygotic ; *Twins, Monozygotic ; }, abstract = {Parents of a sample of 76 same sexed pairs of twins aged 3 to 9 months completed a mailed similarity questionnaire. It included the Bonnelykke et al.'s questionnaire and a four anthropological variable scale. To improve each of these two methods, three other combined methods were carried out and results were compared with the biological zygosity diagnosis. The Bonnelykke et al.'s classification combined with anthropological scale (method 4) gave only 1.2% misclassified in the whole sample. It is concluded that zygosity diagnosis using this type of procedure to distinguish MZ and DZ pairs would be important not only for epidemiological study but also for pediatricians and parents.}, } @article {pmid9062638, year = {1997}, author = {Frezzolini, A and Paradisi, M and Ruffelli, M and Cadoni, S and De Pità, O}, title = {Soluble CD30 in pediatric patients with atopic dermatitis.}, journal = {Allergy}, volume = {52}, number = {1}, pages = {106-109}, doi = {10.1111/j.1398-9995.1997.tb02554.x}, pmid = {9062638}, issn = {0105-4538}, mesh = {Child ; Child, Preschool ; Dermatitis, Atopic/blood/*immunology ; Female ; Humans ; Ki-1 Antigen/*blood ; Male ; Solubility ; }, abstract = {Atopic dermatitis (AD) is a chronic, inflammatory skin disease in which a pathogenetic role of Th2 cells has been supposed. This study investigated the presence of soluble CD30 (sCD30), an activation marker of T-cell clones able to produce Th2-type cytokines, in sera from pediatric patients affected by AD (n = 25) with no symptoms of asthma or rhinitis. The severity of the disease was graded by both the SCORAD and Costa et al. clinical scoring systems. Serum levels of sCD30 were significantly higher in patients with AD in respect to both normal donors (n = 20) and urticaria patients (n = 10), and a positive correlation between serum sCD30 and clinical score was found (r = 0.508; P = 0.01) when AD patients were evaluated by Costa et al.'s method. Furthermore, a significant association (r = 0.443; P = 0.027) between sCD30 and serum levels of the soluble interleukin (IL)-2 receptor (sIL-2R) was observed in AD. The presence of high amounts of sCD30 in atopic patients seems to confirm the role of this molecule as an activation marker useful for in vivo evaluation of a Th2 immune response, and the correlation observed with both clinical score and sIL-2R levels indicates the role of sCD30 as an additional marker of disease activity in pediatric patients with AD.}, } @article {pmid9028028, year = {1997}, author = {Lewicki, P and Hill, T and Czyzewska, M}, title = {Hidden covariation detection: a fundamental and ubiquitous phenomenon.}, journal = {Journal of experimental psychology. Learning, memory, and cognition}, volume = {23}, number = {1}, pages = {221-228}, doi = {10.1037//0278-7393.23.1.221}, pmid = {9028028}, issn = {0278-7393}, support = {MH42715/MH/NIMH NIH HHS/United States ; }, mesh = {Humans ; Neural Pathways/*physiology ; Photic Stimulation ; }, abstract = {H. Hendrickx, J. De Houwer, F. Baeyens, P. Eelen, and E. Van Avermaet (1997) reported a series of (mostly unsuccessful) studies on nonconscious hidden covariation detection (HCD); for example, they reported that out of 3 attempts to replicate P. Lewicki et al.'s studies, only 1 produced the expected results. They concluded that HCD may be not as general and robust as the previous research suggested, and they considered boundary conditions. In this article, the authors discuss a number of weaknesses of H. Hendrickx et al.'s experiments (and systematic deviations from the original methodology) that are potentially responsible for the lack of the expected results and discuss missing facts in their arguments (e.g., they failed to mention any published replications of the HCD studies from other than the present authors' laboratories). It is argued that when all evidence is considered, the proper conclusion is that nonconscious processing of covariations is not only general and robust but also a ubiquitous phenomenon mediating a variety of processes of acquisition of information.}, } @article {pmid9021823, year = {1997}, author = {Hosoda, Y and Miyano, T and Fujimoto, T}, title = {Assay of gamma-glutamyl transpeptidase activity in amniotic fluid offers a possible prenatal diagnosis of biliary atresia in the rat model.}, journal = {Prenatal diagnosis}, volume = {17}, number = {1}, pages = {9-12}, doi = {10.1002/(sici)1097-0223(199701)17:1<9::aid-pd12>3.0.co;2-n}, pmid = {9021823}, issn = {0197-3851}, mesh = {Amniotic Fluid/*enzymology ; Animals ; Biliary Atresia/*diagnosis/embryology/enzymology ; Biomarkers/analysis ; Cholestasis/chemically induced/*enzymology ; Disease Models, Animal ; Female ; Fetal Diseases/*diagnosis/embryology/enzymology ; Liver/embryology/pathology ; Pregnancy ; Prenatal Diagnosis/*methods ; Rats ; Rats, Wistar ; Reference Values ; gamma-Glutamyltransferase/*analysis/metabolism ; }, abstract = {Muller et al. analysed gamma-glutamyl transpeptidase (GGTP) activity in the amniotic fluid of more than 2000 pregnant women for a prenatal diagnosis. They reported that at 18-19 weeks' gestation, two fetuses associated with lower amniotic fluid GGTP levels were diagnosed after birth as having biliary atresia (BA). If low GGTP values correlate closely with BA, chemical assay of amniotic fluid GGTP could possibly be used in the prenatal diagnosis of BA. A fetal model of cholestasis in the rat was created by the administration of the toxic cytopharmacological agent phalloidin on day 15 of gestation, after which amniotic fluid was aspirated and analysed for GGTP. Fetal liver specimens were examined histopathologically. In the normal rats, amniotic fluid GGTP values rose rapidly after 18 days 8 h, reaching a maximum value at 19 days of gestation. Significantly lower GGTP values were observed in the cholestasis models between 18 days 16 h and 19 days 16 h of gestation (P < 0.05). Our data corroborate Muller et al.'s suggestion that fetuses with cholestasis might demonstrate lower GGTP values in their amniotic fluid at a given stage of gestation. Prenatal diagnosis of BA using the amniotic fluid GGTP assay therefore has considerable potential.}, } @article {pmid10456102, year = {1996}, author = {Gluck, MA and Oliver, LM and Myers, CE}, title = {Late-training amnesic deficits in probabilistic category learning: a neurocomputational analysis.}, journal = {Learning & memory (Cold Spring Harbor, N.Y.)}, volume = {3}, number = {4}, pages = {326-340}, doi = {10.1101/lm.3.4.326}, pmid = {10456102}, issn = {1072-0502}, mesh = {Amnesia/*psychology ; Animals ; Humans ; Learning/*physiology ; *Models, Neurological ; Time Factors ; }, abstract = {Building upon earlier behavioral models of animal and human learning, we explore how a psychobiological model of animal conditioning can be applied to amnesic category learning. In particular, we show that the late-training deficit found in Knowlton, Squire, and Gluck's 1994 study of amnesic category learning can be understood as a natural consequence of Gluck and Myers's (1993) theory of hippocampal-region function, a theory that has heretofore been applied only to studies of animal learning. When applied to Knowlton et al.'s category learning task, Gluck and Myers's model assumes that the hippocampal region induces new stimulus representations over multiple training trials that reflect stimulus-stimulus regularities in the training set. As such, the model expects an advantage for control subjects over hippocampal-damaged amnesic patients only later in training when control subjects have developed new hippocampal-dependent stimulus representations; in contrast, both groups are expected to show equivalent performance early in training. A potentially analogous early/late distinction is described for animal studies of stimulus generalization. Our analyses suggest that careful comparisons between early and late-training differences in learning may be an important factor in understanding amnesia and the neural bases of both animal and human learning.}, } @article {pmid8931628, year = {1996}, author = {Pruchno, RA and Patrick, JH and Burant, CJ}, title = {Mental health of aging women with children who are chronically disabled: examination of a two-factor model.}, journal = {The journals of gerontology. Series B, Psychological sciences and social sciences}, volume = {51}, number = {6}, pages = {S284-96}, doi = {10.1093/geronb/51b.6.s284}, pmid = {8931628}, issn = {1079-5014}, support = {R01 MH 46849/MH/NIMH NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Aged ; Aging/*psychology ; Child ; Persons with Disabilities/*psychology ; Female ; Humans ; Mental Health ; Middle Aged ; Models, Theoretical ; }, abstract = {Data were collected from 838 women over age 50 who have either a child with a developmental disability or a child with schizophrenia. Lawton et al.'s (1991) parallel channel hypothesis, which suggests that positive and negative aspects of mental health have differential predictors, was tested. Results indicate that positive caregiving appraisals were predicted by quality of the mother-child relationship, while negative caregiving appraisals were predicted by the amount of help mother provided to her child, mother's health, child's behaviors, and positive appraisals. Positive well-being was predicted by mother's health, positive appraisals, and negative appraisals, while negative well-being was predicted by mother's health, child's behaviors, and negative appraisals. Hence, the data support the usefulness of the hypothesized model.}, } @article {pmid9022248, year = {1996}, author = {McFadyen-Ketchum, SA and Bates, JE and Dodge, KA and Pettit, GS}, title = {Patterns of change in early childhood aggressive-disruptive behavior: gender differences in predictions from early coercive and affectionate mother-child interactions.}, journal = {Child development}, volume = {67}, number = {5}, pages = {2417-2433}, pmid = {9022248}, issn = {0009-3920}, support = {NICHD 30572/HD/NICHD NIH HHS/United States ; NIMH 17146-09/MH/NIMH NIH HHS/United States ; NIMH 42498/MH/NIMH NIH HHS/United States ; }, mesh = {*Affect ; Aggression/*psychology ; Child ; Child Behavior Disorders/diagnosis/*psychology ; Child, Preschool ; *Coercion ; Female ; Follow-Up Studies ; *Gender Identity ; Humans ; Male ; *Mother-Child Relations ; Parenting/psychology ; *Personality Development ; Socialization ; }, abstract = {The present study focused on mother-child interaction predictors of initial levels and change in child aggressive and disruptive behavior at school from kindergarten to third grade. Aggression-disruption was measured via annual reports from teachers and peers. Ordinary least-squares regression was used to identify 8 separate child aggression trajectories, 4 for each gender: high initial levels with increases in aggression, high initial levels with decrease in aggression, low initial levels with increases in aggression, and low initial levels with decreases in aggression. Mother-child interaction measures of coercion and nonaffection collected prior to kindergarten were predictive of initial levels of aggression-disruption in kindergarten in both boys and girls. However, boys and girls differed in how coercion and nonaffection predicted change in aggression-disruption across elementary school years. For boys, high coercion and nonaffection were particularly associated with the high-increasing-aggression trajectory, but for girls, high levels of coercion and nonaffection were associated with the high-decreasing-aggression trajectory. This difference is discussed in the context of Patterson et al.'s coercion training theory, and the need for gender-specific theories of aggressive development is noted.}, } @article {pmid8831315, year = {1996}, author = {Rodríguez, J and Bárcena, M and Alvarez, J}, title = {Axillary brachial plexus anesthesia: electrical versus cold saline stimulation.}, journal = {Anesthesia and analgesia}, volume = {83}, number = {4}, pages = {752-754}, doi = {10.1097/00000539-199610000-00016}, pmid = {8831315}, issn = {0003-2999}, mesh = {Anesthetics, Local/administration & dosage ; Axilla/innervation ; Brachial Plexus/*physiology ; Buffers ; Cold Temperature ; Electric Stimulation ; Female ; Forearm/surgery ; Hand/surgery ; Humans ; Male ; Mepivacaine/administration & dosage ; Middle Aged ; Motor Neurons/drug effects ; Muscle Contraction/drug effects ; Nerve Block/*methods ; Paresthesia/physiopathology ; Sensation/physiology ; Sodium Bicarbonate ; Sodium Chloride ; }, abstract = {The aim of this study was to investigate which of two methods of nerve stimulation, cold saline-induced paresthesia or use of a nerve stimulator, was more effective in increasing the successful brachial plexus block rate by the axillary approach. Twenty patients were randomly assigned to Group A (saline below 11 degrees C), and 20 patients to Group B (nerve stimulator). All blocks were performed by the same anesthesiologist using 40 mL of 1.5% mepivacaine and 4 mL of 8.4% sodium bicarbonate. Successful block was defined using Vester-Andersen et al.'s criteria. Cold saline-induced paresthesiae in the hand or forearm were obtained in 19 patients (95%) during one of four attempts allowed, and in 15 patients (75%) on the first attempt. A motor response was evoked by a nerve stimulator in 17 patients (85%). Two patients (10%) had a paresthesia in the hand without a motor response with the current at less than 1 mA. A successful block was achieved in 19 patients in each group.}, } @article {pmid8917379, year = {1996}, author = {Sakurai, K and Yoshiga, K and Tsumura, M and Takada, K}, title = {Effects of thermochemotherapy [1-hexylcarbamoyl-5-fluorouracil (HCFU) combined with hyperthermia]: a basic study on the most effective timing and sequence in vivo.}, journal = {Anticancer research}, volume = {16}, number = {5A}, pages = {2729-2733}, pmid = {8917379}, issn = {0250-7005}, mesh = {Animals ; Antineoplastic Agents/*administration & dosage/pharmacokinetics ; Carcinoma, Ehrlich Tumor/therapy ; Combined Modality Therapy ; Drug Administration Schedule ; Fluorouracil/administration & dosage/*analogs & derivatives/pharmacokinetics ; *Hyperthermia, Induced ; Male ; Mice ; Tissue Distribution ; }, abstract = {1-Hexylcarbamoyl-5-fluorouracil (HCFU) is known to be hydrolyzed to 5-fluorouracil (5-FU) by heating. We have previously reported the enhancement of the antitumor effects of HCFU when combined with hyperthermia (1). This study aimed at determining the most effective timing schedule for HCFU combined with hyperthermia for clinical application. On the third, 6th, 9th, 12th and 15th day after transplantation, HCFU (80 mg/kg) was administered and hyperthermia induced. The antitumor effect was evaluated by the measurement of tumor volume. 5-FU concentration in the tumor tissue was analyzed on the 12th day after transplantation after administering 150 mg/kg HCFU, with or without hyperthermia (43.5 degrees C, 45 min). 5-FU concentration in serum and other tissues (kidney, liver and submandibular gland) were also analyzed. The concentration was measured by a high performance liquid chromatograph (HPLC) following Mori et al 's method (2). An enhanced antitumor effect and a significant increase in 5-FU concentration in tumor tissue were observed in post-heated groups of mice as compared with pre-heated groups and groups given HCFU alone. The results showed that HCFU given 1 to 2 hours prior to hyperthermia was the most effective treatment.}, } @article {pmid8891989, year = {1996}, author = {Weinzweig, N and Sharzer, LA and Starker, I}, title = {Replantation and revascularization at the transmetacarpal level: long-term functional results.}, journal = {The Journal of hand surgery}, volume = {21}, number = {5}, pages = {877-883}, doi = {10.1016/S0363-5023(96)80208-5}, pmid = {8891989}, issn = {0363-5023}, mesh = {Adult ; Amputation, Traumatic/*surgery ; Finger Injuries/physiopathology/*surgery ; Fingers/physiopathology/*surgery ; Follow-Up Studies ; Hand/physiopathology/*surgery ; Hand Injuries/physiopathology/*surgery ; Hand Strength/physiology ; Humans ; Male ; Metacarpus/*injuries ; Range of Motion, Articular/physiology ; *Replantation ; Retrospective Studies ; Thumb/injuries/physiopathology/*surgery ; Time Factors ; }, abstract = {Thirteen consecutive transmetacarpal replantations and revascularizations in 12 patients were reviewed retrospectively. Ten patients (11 hands) sustained crush injuries, 1 withstood an explosive blast, and 1 suffered a guillotine amputation. Nine revascularizations (1 thumb and 31 fingers) and 4 replantations (1 thumb and 16 fingers), including bilateral procedures in 1 patient, were performed. Forty-four of 49 replantable digits (90%) were salvaged. Ten patients (11 hands) required secondary surgery (mean, 4.5 procedures per hand), 29 of 49 (60%) for tendon and joint scarring and 7 of 20 (14%) for nonunions or malunions. Range of motion averaged 109 degrees per digit. Intrinsic muscle function and pinch and grip strengths were weak or absent. Recovery of sensibility was poor. According to Chen et al.'s grading system of functional return, 4 (31%) were grade II, 4 (31%) were grade III, and 5 (38%) grade IV. The follow-up period ranged from 2.5 to 11 years. Only 1 patient resumed his prior occupation (as supervisor); 2 were permanently disabled, 3 pursued new and unrelated occupations, 2 were still in therapy, and 4 were lost to late follow-up evaluation. None of the manual laborers (11 patients) were able to return to their preinjury livelihood. Despite these discouragingly poor results, all patients were satisfied with the surgery.}, } @article {pmid8878702, year = {1996}, author = {Takezaki, N and Nei, M}, title = {Genetic distances and reconstruction of phylogenetic trees from microsatellite DNA.}, journal = {Genetics}, volume = {144}, number = {1}, pages = {389-399}, pmid = {8878702}, issn = {0016-6731}, mesh = {*DNA, Satellite ; Genetic Variation ; *Mathematical Computing ; *Microsatellite Repeats ; *Models, Genetic ; *Phylogeny ; Sample Size ; }, abstract = {Recently many investigators have used microsatellite DNA loci for studying the evolutionary relationships of closely related populations or species, and some authors proposed new genetic distance measures for this purpose. However, the efficiencies of these distance measures in obtaining the correct tree topology remains unclear. We therefore investigated the probability of obtaining the correct topology (PC) for these new distances as well as traditional distance measures by using computer simulation. We used both the infinite-allele model (IAM) and the stepwise mutation model (SMM), which seem to be appropriate for classical markers and microsatellite loci, respectively. The results show that in both the IAM and SMM CAVALLI-SFORZA and EDWARDS' chord distance (DC) and NEI et al.'s DA distance generally show higher PC values than other distance measures, whether the bottleneck effect exists or not. For estimating evolutionary times, however, NEI's standard distance and GOLDSTEIN et al.'s (delta mu)2 are more appropriate than other distances. Microsatellite DNA seems to be very useful for clarifying the evolutionary relationships of closely related populations.}, } @article {pmid8853866, year = {1996}, author = {Johnstone, B}, title = {An editorial response to Smith-Knapp et al.'s 'Predicting independence from neuropsychological tests following traumatic brain injury'.}, journal = {Brain injury}, volume = {10}, number = {9}, pages = {627-630}, doi = {10.1080/026990596124052}, pmid = {8853866}, issn = {0269-9052}, mesh = {Activities of Daily Living ; Brain Injuries/*classification/psychology ; Cognition ; Humans ; *Neuropsychological Tests ; }, } @article {pmid8853109, year = {1996}, author = {Jackson, RR}, title = {Reali-Forster et al.'s gilled endotracheal tube is a modification of Miller and Sethi's old design.}, journal = {Anesthesiology}, volume = {85}, number = {3}, pages = {690}, doi = {10.1097/00000542-199609000-00041}, pmid = {8853109}, issn = {0003-3022}, mesh = {Humans ; Intubation, Intratracheal/*instrumentation ; }, } @article {pmid8710452, year = {1996}, author = {Rayner, K and Fischer, MH}, title = {Mindless reading revisited: eye movements during reading and scanning are different.}, journal = {Perception & psychophysics}, volume = {58}, number = {5}, pages = {734-747}, pmid = {8710452}, issn = {0031-5117}, support = {HD26765/HD/NICHD NIH HHS/United States ; MH01255/MH/NIMH NIH HHS/United States ; }, mesh = {Adult ; *Attention ; Electrooculography ; *Eye Movements ; Female ; Fixation, Ocular ; Humans ; Male ; Psychophysics ; *Reading ; Saccades ; Signal Processing, Computer-Assisted ; }, abstract = {In an extension of a study by Vitu, O'Regan, Inhoff, and Topolski (1995), we compared global and local characteristics of eye movements during (1) reading, (2) the scanning of transformed text (in which each letter was replaced with a z), and (3) visual search. Additionally, we examined eye behavior with respect to specific target words of high or low frequency. Globally, the reading condition led to shorter fixations, longer saccades, and less frequent skipping of target strings than did scanning transformed text. Locally, the manipulation of word frequency affected fixation durations on the target word during reading, but not during visual search or z-string scanning. There were also more refixations on target words in reading than in scanning. Contrary to Vitu et al.'s (1995) findings, our results show that eye movements are not guided by a global strategy and local tactics, but by immediate processing demands.}, } @article {pmid8795057, year = {1996}, author = {Bayen, UJ and Murnane, K}, title = {Aging and the use of perceptual and temporal information in source memory tasks.}, journal = {Psychology and aging}, volume = {11}, number = {2}, pages = {293-303}, doi = {10.1037//0882-7974.11.2.293}, pmid = {8795057}, issn = {0882-7974}, mesh = {Adolescent ; Adult ; Age Factors ; Aged ; Aging/*psychology ; Female ; Humans ; Male ; *Memory ; Middle Aged ; *Time Perception ; }, abstract = {A number of studies have reported age differences in memory for the source of information. S.A. Ferguson, S. Hashtroudi, and M.K. Johnson (1992) suggested that older adults do not efficiently use multiple distinctive characteristics of sources to distinguish between sources in source memory tasks. In the study reported here, participants heard information from 2 sources and later decided whether test items had been presented by Source A, by Source B, or were new. The distinctiveness of both perceptual and temporal characteristics of sources were independently manipulated. Older adults benefited more than young adults from multiple distinctive characteristics of sources. These results question the generality of S.A. Ferguson et al.'s hypothesis.}, } @article {pmid8696235, year = {1996}, author = {}, title = {Comments on Hall et al.'s Australian National Drug Strategy Monograph no. 25 "The health and psychological consequences of cannabis use".}, journal = {Addiction (Abingdon, England)}, volume = {91}, number = {6}, pages = {759-762}, pmid = {8696235}, issn = {0965-2140}, mesh = {Adolescent ; Adult ; Australia ; Cannabinoids/*adverse effects ; Child ; Female ; Humans ; Infant, Newborn ; Male ; Marijuana Abuse/*psychology ; Marijuana Smoking/*adverse effects/psychology ; Pregnancy ; Risk Factors ; }, } @article {pmid8667647, year = {1996}, author = {Estey, E}, title = {Treatment of refractory AML.}, journal = {Leukemia}, volume = {10}, number = {6}, pages = {932-936}, pmid = {8667647}, issn = {0887-6924}, mesh = {Adolescent ; Adult ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Bayes Theorem ; Bone Marrow Transplantation ; Child ; Child, Preschool ; Combined Modality Therapy ; Humans ; Infant ; Leukemia, Myeloid, Acute/drug therapy/*therapy ; Middle Aged ; Remission Induction ; Research Design ; Salvage Therapy ; }, abstract = {Refractory AML is variously defined. MD Anderson data indicate that patients with AML that stayed in first remission for less than 2 years are incurable with standard chemotherapy regimens, hence meriting a definition of refractory; the prognosis of patients whose first remissions are longer is on average similar to that of untreated patients. Within the refractory group, Hiddeman et al' s definition (Leukemia 1990; 4: 184-188) is elaborated to account for the number of courses of initial therapy and for response to prior salvage regimens. If patients with refractory AML cannot receive an allogeneic transplant, the standard of therapy should be investigational chemotherapy regimens. A new Bayesian pre-phase II designed is described for use in testing such regimens.}, } @article {pmid8655802, year = {1996}, author = {Nix, DA and Papcun, G and Hogden, J and Zlokarnik, I}, title = {Two cross-linguistic factors underlying tongue shapes for vowels.}, journal = {The Journal of the Acoustical Society of America}, volume = {99}, number = {6}, pages = {3707-3717}, doi = {10.1121/1.414968}, pmid = {8655802}, issn = {0001-4966}, mesh = {Cross-Cultural Comparison ; Humans ; Iceland ; Linguistics ; *Phonetics ; Speech/*physiology ; Speech Production Measurement ; Tongue/*physiology ; United States ; }, abstract = {Desirable characteristics of a vocal-tract parametrization include accuracy, low dimensionality, and generalizability across speakers and languages. A low-dimensional, speaker-independent linear parametrization of vowel tongue shapes can be obtained using the PARAFAC three-mode factor analysis procedure [Harshman et al., J. Acoust. Soc. Am. 62, 693-707 (1977)]. Harshman et al. applied PARAFAC to midsagittal x-ray vowel data from five English speakers, reporting that two speaker-independent factors are required to accurately represent the tongue shape measured along anatomically normalized vocal-tract diameter grid lines. Subsequently, the cross-linguistic generality of this parametrization was brought into question by the application of PARAFAC to Icelandic vowel data, where three nonorthogonal factors were reported [Jackson, J. Acoust. Soc. Am. 84, 124-143 (1988)]. This solution is shown to be degenerate; a reanalysis of Jackson's Icelandic data produces two factors that match Harshman et al.'s factors for English vowels, contradicting Jackson's distinction between English and Icelandic language-specific "articulatory primes". To obtain vowel factors not constrained by artificial measurement grid lines, x-ray tongue shape traces of six English speakers were marked with 13 equally spaced points. PARAFAC analysis of this unconstrained (x,y) coordinate data results in two factors that are clearly interpretable in terms of the traditional vowel quality dimensions front/back, high/low.}, } @article {pmid8835689, year = {1996}, author = {Koslowsky, M and Solomon, Z and Bleich, A and Laor, N}, title = {Effects of stressful stimuli: a comparison between two time periods.}, journal = {Journal of clinical psychology}, volume = {52}, number = {3}, pages = {279-283}, doi = {10.1002/(SICI)1097-4679(199605)52:3<279::AID-JCLP4>3.0.CO;2-N}, pmid = {8835689}, issn = {0021-9762}, support = {1R03 MH49007-0/MH/NIMH NIH HHS/United States ; }, mesh = {*Adaptation, Psychological ; Adult ; *Arousal ; Awareness ; Combat Disorders/*diagnosis/psychology ; Female ; Follow-Up Studies ; Humans ; Indian Ocean ; Male ; *Mental Recall ; Middle Aged ; Personality Inventory ; Stress, Psychological/*complications ; Urban Population ; Warfare ; }, abstract = {Studies of the effects of stressful stimuli that occurred sometime in the past have generally found both intrusion and avoidance as consequences. The present investigation used Horowitz et al.'s (1979) Impact of Events Scale to compare the responses of victims who had been recently evacuated to a hotel after a missile attack on their home with a similar group one year later. Although during the attacks intrusion responses were found to be significantly higher than avoidance, the means on the two mental states did not differ significantly one year after. In addition, intrusion was found to be more highly correlated with several functioning measures; this latter trend becoming more pronounced at Time 2. Implications of the findings and limitations of the study were mentioned.}, } @article {pmid8605177, year = {1996}, author = {Borgstahl, GE and Parge, HE and Hickey, MJ and Johnson, MJ and Boissinot, M and Hallewell, RA and Lepock, JR and Cabelli, DE and Tainer, JA}, title = {Human mitochondrial manganese superoxide dismutase polymorphic variant Ile58Thr reduces activity by destabilizing the tetrameric interface.}, journal = {Biochemistry}, volume = {35}, number = {14}, pages = {4287-4297}, doi = {10.1021/bi951892w}, pmid = {8605177}, issn = {0006-2960}, support = {GM23658/GM/NIGMS NIH HHS/United States ; GM48495/GM/NIGMS NIH HHS/United States ; //Wellcome Trust/United Kingdom ; }, mesh = {Binding Sites ; Electrochemistry ; Enzyme Stability ; Genetic Variation ; Humans ; In Vitro Techniques ; Models, Molecular ; Molecular Sequence Data ; Molecular Structure ; Mutagenesis, Site-Directed ; Oxidative Stress ; Phenotype ; Point Mutation ; Polymorphism, Genetic ; Protein Conformation ; Superoxide Dismutase/*chemistry/genetics/*metabolism ; Temperature ; }, abstract = {Human manganese superoxide dismutase (MnSOD) is a homotetrameric enzyme which protects mitochondria against oxygen-mediated free radical damage. Within each subunit, both the N-terminal helical hairpin and C-terminal alpha/beta domains contribute ligands to the catalytic manganese site. Two identical four-helix bundles, symmetrically assembled from the N-terminal helical hairpins, form a novel tetrameric interface that stabilizes the active sites. The 2.5 A crystallographic structure of the naturally occurring polymorphic variant Ile58Thr MnSOD reveals that the helical hairpin mutation Thr58 causes two packing defects in each of the two four-helix bundles of the tetrameric interface. Similar mutations, expected to cause packing defects in the Cu,ZnSOD dimer interface, are associated with the degenerative disease amyotrophic lateral sclerosis. Ile58Thr MnSOD is primarily dimeric in solution and is significantly less thermostable than the normal enzyme, with decreases of 15 degrees C in the main melting temperature and 20 degrees C in the heat-inactivation temperature. Consequently, this mutant MnSOD is compromised at normal body temperatures: thermal inactivation, predicted from the decrease in thermal stability, occurs with a theoretical half-life of only 3.2 h at 37 degrees C (1.4 h at 41 degrees C), compared with 3.1 years for native MnSOD. This prediction is supported by direct measurements: incubation at 41.7 degrees C for 3 h has no effect on the activity of native MnSOD but completely inactivates mutant MnSOD. Rapid inactivation of Ile58Thr MnSOD at the elevated temperatures associated with fever and inflammation could provide an early advantage by killing infected cells, but also would increase superoxide-mediated oxidative damage and perhaps contribute to late-onset diseases.}, } @article {pmid8857371, year = {1996}, author = {Rutter, M}, title = {Comments on Fergusson et al.'s "Alcohol misuse and juvenile offending in adolescence".}, journal = {Addiction (Abingdon, England)}, volume = {91}, number = {4}, pages = {495-498}, pmid = {8857371}, issn = {0965-2140}, mesh = {Adolescent ; Adolescent Behavior ; *Alcoholism ; Female ; Humans ; *Juvenile Delinquency ; Male ; New Zealand ; }, } @article {pmid8799768, year = {1996}, author = {Furedy, JJ}, title = {Some elementary distinctions among, and comments concerning, the 'control' question 'test' (CQT) polygrapher's many problems: a reply to Honts, Kircher and Raskin.}, journal = {International journal of psychophysiology : official journal of the International Organization of Psychophysiology}, volume = {22}, number = {1-2}, pages = {53-59}, doi = {10.1016/0167-8760(96)00007-4}, pmid = {8799768}, issn = {0167-8760}, mesh = {Ethics, Professional ; Humans ; Lie Detection/*psychology ; }, abstract = {Although the title of Honts et al.'s paper suggests that it will be a reply to the specific, logico-ethical problem of the CQT polygraph (the Polygrapher's Dilemma), the text deals only tangentially with this logico-ethical problem, and engages, instead, in a diffuse discussion of related, but different, ethical, methodological, and empirical problems of the CQT polygraph. This paper seeks to restore some clarity to the discussion by reminding us of certain basic distinctions among logico-ethical, ethical, methodological, and empirical problems. In the light of these distinctions, the relevant literature, and the essential characteristics of the CQT (which continue to be obscured by the use of systematically misleading terminology), I stand by my claim that, on the ethico-logical grounds (i.e. the CQT Polygrapher's Dilemma formulated in my 1993 paper [1]), as well as ethical, methodological, and evidential grounds (which have been detailed elsewhere), the CQT should be abandoned as a serious method of detecting deception, no matter how useful it may be to practitioners as an interrogatory prop.}, } @article {pmid8642628, year = {1996}, author = {Dal Monte, P and Bessia, C and Ripalti, A and Landini, MP and Topilko, A and Plachter, B and Virelizier, JL and Michelson, S}, title = {Stably expressed antisense RNA to cytomegalovirus UL83 inhibits viral replication.}, journal = {Journal of virology}, volume = {70}, number = {4}, pages = {2086-2094}, pmid = {8642628}, issn = {0022-538X}, mesh = {Antiviral Agents/biosynthesis ; Base Sequence ; Cell Line ; Cytomegalovirus/*genetics/physiology ; DNA Primers ; DNA, Viral/biosynthesis ; Humans ; Interferons/biosynthesis ; Molecular Sequence Data ; Phosphoproteins/*metabolism ; RNA, Antisense/*genetics ; RNA, Viral/*genetics ; Tumor Cells, Cultured ; Viral Matrix Proteins/*metabolism ; Viral Proteins/biosynthesis ; *Virus Replication/genetics ; }, abstract = {The human cytomegalovirus (HCMV) open reading frame UL83 encodes a phosphoprotein of 64 to 68kDa (pp65) which is a major constituent of this virion and dense bodies. To determine the importance of the HCMV gene in the virus cycle, we studied HCMV replication in astrocytoma cells stably transfected with a retroviral vector carrying an antisense UL83 cDNA. Reverse transcription-PCR detected antisense RNA in the cytoplasm. The steady-state level of a 4-kb RNA containing coding sequences for pp65 was significantly reduced after infection of antisense cells. Concomitant with this, levels of expression of pp65 and pp71 (UL82) were severely reduced. Extracellular HCMV production was almost completely blocked, irrespective of the multiplicity of infection or the time after infection studied. The block occurred at an early phase, since immediate-early protein synthesis occurred normally, while several late proteins (e.g., pp150 [ppUL32] and assembly protein [UL80]) were absent or strongly inhibited. Normal replication of herpes simplex virus and of a pp65 deletion mutant of HCMV (RVAd65), lacking target sequences of antisense RNA, demonstrated the specificity of the block for wild-type HCMV in the antisense-stabilized cells and indicated that the block was not due to indirect interference with cellular genes. Our results appear to contradict those of Schmolke et al (S. Schmolke, H.F. Kern, P. Drescher, G. Jahn, and B. Plachter, J. Virol. 69:5959-5968, 1995), which show that UL83 is a nonessential gene for HCMV replication in vitro. This contradiction is discussed in light of the fact that the 4-kb mRNA, which codes for pp65 and was targeted in UL83-antisense cell lines, may be a bicistronic mRNA which also codes for pp71 (UL82). Thus, interference of expression from the genes encoding pp65 and pp71 by blocking of this putative bicistronic message leads to severe impairment of viral replication.}, } @article {pmid16203347, year = {1996}, author = {Single, E and de Burgh, S}, title = {Comments on Stockwell et al.'s "Unravelling the preventive paradox for acute alcohol problems", followed by the authors' response.}, journal = {Drug and alcohol review}, volume = {15}, number = {1}, pages = {17-20; discussion 20}, doi = {10.1080/09595239600185621}, pmid = {16203347}, issn = {0959-5236}, } @article {pmid8934598, year = {1996}, author = {Lipsitz, SR and Parzen, M}, title = {A jackknife estimator of variance for Cox regression for correlated survival data.}, journal = {Biometrics}, volume = {52}, number = {1}, pages = {291-298}, pmid = {8934598}, issn = {0006-341X}, support = {AI 246431/AI/NIAID NIH HHS/United States ; CA 55576/CA/NCI NIH HHS/United States ; GM 29745/GM/NIGMS NIH HHS/United States ; }, mesh = {Acquired Immunodeficiency Syndrome/drug therapy ; Analysis of Variance ; Biometry/methods ; Humans ; *Proportional Hazards Models ; Ribavirin/therapeutic use ; *Survival Analysis ; }, abstract = {Studies in the health sciences often give rise to correlated survival data. Wei, Lin, and Weissfeld (1989, Journal of the American Statistical Association 84, 1065-1073) and Lee, Wei, and Amato (1992, in Survival Analysis: State of the Art) showed that, if the marginal distributions of the correlated survival times follow a proportional hazards model, then the estimates from Cox's partial likelihood (Cox, D.R., 1972, Journal of the Royal Statistical Society, Series B 24, 187-220), naively treating the correlated survival times as independent, give consistent estimates of the relative risk parameters. However, because of the correlation between survival times, the inverse of the information matrix may not be a consistent estimate of the asymptotic variance. Wei et al. (1989) and Lee et al. (1992) proposed a robust variance estimate that is consistent for the asymptotic variance. We show that a "one-step" jackknife estimator of variance is asymptotically equivalent to their variance estimator. The jackknife variance estimator may be preferred because an investigator needs only to write a simple loop in a computer package instead of a more involved program to compute Wei et al. (1989) and Lee et al.'s (1992) estimator.}, } @article {pmid8851739, year = {1996}, author = {Engebretson, PH and Huttenlocher, J}, title = {Bias in spatial location due to categorization: comment on Tversky and Schiano.}, journal = {Journal of experimental psychology. General}, volume = {125}, number = {1}, pages = {96-108}, doi = {10.1037//0096-3445.125.1.96}, pmid = {8851739}, issn = {0096-3445}, support = {R01 MH45402/MH/NIMH NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; *Attention ; Concept Formation ; *Discrimination Learning ; Female ; Field Dependence-Independence ; Humans ; Male ; *Orientation ; *Pattern Recognition, Visual ; *Psychomotor Performance ; Psychophysics ; }, abstract = {B. Tversky and D. J. Schiano (1989) reported bias in reproducing the angle of a line in an "ell" frame. When no conceptual interpretation of the task was given, they argued that the bias was due to a perceptual process that produced an apparent tilt in the line (D. J. Schiano & B. Tversky, 1992). We propose that J. Huttenlocher, L. V. Hedges, and S. Duncan's (1991) model of category effects on estimates of stimulus values provides a better explanation of this bias. Two experiments are presented that examine these alternative views. The results show effects of the orientation of the frame and of an interference task on bias that are more consistent with J. Huttenlocher et al.'s model than with the perceptual explanation adopted by D. J. Schiano and B. Tversky.}, } @article {pmid8737009, year = {1996}, author = {Allen, D}, title = {Are alcoholic women more likely to drink premenstrually?.}, journal = {Alcohol and alcoholism (Oxford, Oxfordshire)}, volume = {31}, number = {2}, pages = {145-147}, doi = {10.1093/oxfordjournals.alcalc.a008125}, pmid = {8737009}, issn = {0735-0414}, mesh = {Adult ; Alcohol Drinking/prevention & control/*psychology ; Alcoholism/*psychology/rehabilitation ; Female ; Humans ; Middle Aged ; Motivation ; Personality Inventory ; Premenstrual Syndrome/*psychology ; Risk Factors ; Treatment Outcome ; }, abstract = {A retrospective questionnaire study of alcoholic women attending a clinic for abstaining alcoholics, a voluntary agency and a drop-in centre for people with alcohol problems was conducted over a 2-year period. The women were asked whether they experienced premenstrual symptoms based on Halbreich et al.'s Premenstrual Assessment Form (PAF) [Halbreich et al. (1982) Acta Psychiatrica Scandinavica 65, 46-65] and were also administered the severity of Alcohol Dependence Questionnaire (SADQ). The results showed that one-third of women drank more premenstrually than at other times of the month. It is concluded that knowledge of high-risk times of the month can aid counselling for this group of women.}, } @article {pmid8932409, year = {1996}, author = {Braithwaite, V}, title = {Between stressors and outcomes: can we simplify caregiving process variables?.}, journal = {The Gerontologist}, volume = {36}, number = {1}, pages = {42-53}, doi = {10.1093/geront/36.1.42}, pmid = {8932409}, issn = {0016-9013}, mesh = {*Adaptation, Psychological ; Adult ; Aged ; Aged, 80 and over ; Caregivers/*psychology ; Cost of Illness ; Female ; Frail Elderly/*psychology ; Health Resources ; Humans ; Male ; Middle Aged ; Social Support ; Stress, Psychological/*complications ; Workload/psychology ; }, abstract = {Lawton, Kleban, Moss, Rovine & Glicksman's (1989) construction of caregiving appraisal is examined through a principal components analysis and varimax rotation of a data set based on in-depth quantitative interviews with 144 caregivers. Five caregiving appraisal dimensions were identified. Two dealt specifically with the provision of care: "task load caregiving" and "dysfunctional caregiving." The remaining three were primarily concerned with social supportiveness: "intimacy and love," "social captivity," and "social distance." "Dysfunctional caregiving" was the only type of appraisal that had significant bivariate relationships with poor mental health, low psychological well-being and subsequent institutionalization. A sixth dimension identified in this analysis, "inner strength and efficacy," represented psychological resources. Its independence from the appraisal measures supports Lawton et al.'s (1989) assumption that resources and appraisals can be measured separately. In contrast, social resources are better conceptualized as an integral part of caregiving appraisals.}, } @article {pmid8835285, year = {1996}, author = {Wallace, S}, title = {A critique of Hawthorne et al.'s evaluation of life education.}, journal = {Addiction (Abingdon, England)}, volume = {91}, number = {2}, pages = {286-291}, doi = {10.1111/j.1360-0443.1996.tb03191.x}, pmid = {8835285}, issn = {0965-2140}, mesh = {Evaluation Studies as Topic ; *Health Education ; Humans ; *Illicit Drugs ; Politics ; *Psychotropic Drugs ; Substance-Related Disorders/*prevention & control ; }, } @article {pmid8746235, year = {1996}, author = {Rayner, K and Pollatsek, A}, title = {Reading unspaced text is not easy: comments on the implications of Epelboim et al.'s (1994) study for models of eye movement control in reading.}, journal = {Vision research}, volume = {36}, number = {3}, pages = {461-470}, doi = {10.1016/0042-6989(95)00132-8}, pmid = {8746235}, issn = {0042-6989}, support = {HD 26765/HD/NICHD NIH HHS/United States ; }, mesh = {Eye Movements/*physiology ; Fixation, Ocular ; Humans ; Models, Biological ; *Reading ; Saccades ; }, abstract = {Epelboim, Booth, and Steinman [1994 Vision Research, 34, 1735-1766] recently published an article in this journal in which they argued that "unspaced text is relatively easy to read" (p. 1760). From this they concluded that the spaces between words "are relatively unimportant for guiding reading eye movements" (p. 1760). We have serious reservations concerning these conclusions. In this letter we argue that (1) reading unspaced text is not easy for most readers and (2) there are more diagnostic ways to examine the role of spacing. We also comment on the implications for models of eye movements in reading.}, } @article {pmid8746224, year = {1996}, author = {Cobo-Lewis, AB}, title = {Monocular dot-density cues in random-dot stereograms.}, journal = {Vision research}, volume = {36}, number = {3}, pages = {345-350}, doi = {10.1016/0042-6989(95)00124-7}, pmid = {8746224}, issn = {0042-6989}, mesh = {*Cues ; Humans ; Models, Biological ; Pattern Recognition, Visual/*physiology ; Psychophysics/methods ; Vision Disparity/physiology ; Vision, Monocular/*physiology ; }, abstract = {In the original random-dot stereograms (RDSs) invented by Julesz, binocular disparity could only take on values that were integral multiples of dot width. The other common method for constructing RDSs (the projection method) relaxes this restriction. However, the projection method can introduce dot-density cues into the monocular images. When polar projection is employed, density variation is introduced as an expression of perspective cues; when parallel projection is employed, there are no perspective cues, but density variation is nonetheless introduced whenever disparity varies as a function of horizontal position. de Vries, Kappers, and Koenderink [(1994) Vision Research, 34, 2409-2423] proposed to minimize the density cues by selecting half of the random dots from a uniform random distribution in the right-eye image, projecting them onto the cyclopean surface, and then projecting them back to the left eye image and vice versa. In this paper the precise nature of the density cues introduced by the projection method, and by de Vries et al.'s modification of that method, are derived. It is also shown that the projection method and its modification have very similar density cues near the medial sagittal plane when polar projection is employed, and that they have identical density cues over the entire random-dot field when parallel projection is employed.}, } @article {pmid14588932, year = {1996}, author = {Mittenberg, W and Rotholc, A and Russell, E and Heilbronner, R}, title = {Identification of malingered head injury on the Halstead-Reitan battery.}, journal = {Archives of clinical neuropsychology : the official journal of the National Academy of Neuropsychologists}, volume = {11}, number = {4}, pages = {271-281}, pmid = {14588932}, issn = {0887-6177}, abstract = {Heaton et al. (1978) demonstrated that the performance of malingerers and actual head trauma patients could be distinguished on the HRB by discriminant analysis. The present study replicated Heaton et al.'s methodology on a larger sample to provide a more stable function for discriminating simulated and real head trauma. Malingerers (n = 80) were instructed to fake severe deficits without being obvious. Patients (n = 80) had documented trauma and were not litigating for compensation. Groups were matched on age, gender, and overall Impairment Index to permit comparisons between patterns of performance. A crossvalidated step-wise discriminant function correctly identified 88.75% of the groups, with 83.8% true positives and 93.8% true negatives. This function was applied to several published data sets. Both malingerer and patient groups were accurately identified in Heaton et al. (1978) and Trueblood and Schmidt (1993). Faust et al.'s (1988) adolescent malingerer and the malingered performance of three litigating patients published by Cullum et al. (1991), were also correctly classified.}, } @article {pmid14588456, year = {1996}, author = {Johnstone, B and Callahan, CD and Kapila, CJ and Bouman, DE}, title = {The comparability of the WRAT-R reading test and NAART as estimates of premorbid intelligence in neurologically impaired patients.}, journal = {Archives of clinical neuropsychology : the official journal of the National Academy of Neuropsychologists}, volume = {11}, number = {6}, pages = {513-519}, pmid = {14588456}, issn = {0887-6177}, abstract = {A study by Wiens, Bryan, and Crossen (1993) suggests the Wide Range Achievement Test-Revised (WRAT-R) Reading subtest and North American Adult Reading Test (NAART) are adequate predictors of Wechsler Adult Intelligence Scale-Revised (WAIS-R) IQ scores for a normal population. Although it is common practice to use reading scores to estimate premorbid IQ in clinical populations, the WRAT-R and NAART have not been compared using individuals with brain dysfunction. The current study cross-validated the Wiens et al. (1993) study using neurologically impaired populations: traumatic brain injury (n = 118), dementia (n = 37), and other neurologic impairments (n = 77). The results were generally consistent across all three groups: (a) the WRAT-R and NAART were equivalent and accurate estimates of average VIQ levels; (b) the WRAT-R and NAART were equivalent but underestimates of higher intelligence ranges; and (c) the WRAT-R is a more accurate estimate for lower VIQ ranges, although both are overestimates. This third finding is in contrast to Wiens et al.'s (1993) results that suggest the WRAT-R is an accurate estimate of lower IQ ranges for normals. It is concluded that the WRAT-R is the preferred measure of premorbid verbal intelligence for psychometric and clinical reasons.}, } @article {pmid10388003, year = {1996}, author = {Oliver, RT}, title = {Regarding: Valero V, Buzdar AU, Hortobagyi GN. "Locally Advanced Breast Cancer," The Oncologist 1996;1:8-17.}, journal = {The oncologist}, volume = {1}, number = {4}, pages = {278-279}, pmid = {10388003}, issn = {1549-490X}, abstract = {To the Editors: I read with interest Valero et al.'s review showing a lack of any increased cure rate over surgery from use of neoadjuvant combination therapy for locally advanced breast cancer, although a definite gain from breast conservation. Missing was any mention of hormone therapy [1] despite some of the best neoadjuvant results being from the use of Tamoxifen&reg; in the elderly [2]. Interestingly, the highest complete remission rate in Valero et al.'s review (52%) was in a regimen including Tamoxifen&reg; [3]. In addition, Bartlett et al. have reported that hormone therapy is superior to chemotherapy as adjuvant in estrogen receptor-positive tumors [4]. With new data from the study of radiotherapy demonstrating prostate tumor cell kill to be far higher when radiation treatment follows hormone therapy rather than when given concurrently or after therapy [5], there is a need for studies to investigate whether the same applies to hormone therapy when combined with chemotherapy in breast cancer. Further support for this comes from the latest overview of the effect of menstrual cycle timing and breast cancer surgery. The greatest gain from operating on premenopausal women occurs when the operation takes place during the progestergenic phase of the menstrual cycle, particularly in advanced node-positive patients and those with high levels of progesterone pre-op attributed to high survival [6]. With increasing recognition that trauma-induced cytokine release can be a factor in tumor acceleration [7], there is a case to consider hormones followed by chemotherapy plus radiation before any major surgical interference [1], most particularly in the rare subgroup of poor-risk tumors arising during pregnancy [8]. AUTHORS' RESPONSE: We appreciate the comments of Professor Oliver regarding our review. It has been recognized for decades that breast cancer is a systemic disease. Regional and distant micro- metastases occur early, and are part of the natural history of this illness. Adjuvant chemotherapy is an integral part of the curative management of patients with primary breast cancer, including locally advanced breast cancer (LABC). The benefit derived from this therapeutic approach is well documented, and persists beyond 10 years of follow-up [1, 2]. While we recognize the paucity of studies in direct support of this statement in patients with operable LABC, a few randomized trials have been completed and published [3, 4], and the world overview of randomized trials also demonstrated this benefit [1, 2]. Several randomized studies are under way to assess the relative efficacy of primary (or neoadjuvant) versus adjuvant chemotherapy in patients with early breast cancer, as well as operable LABC. For patients with inoperable LABC the window of opportunity to perform randomized trials with local therapy only as a control arm was lost many years ago. However, the results of phase II trials compare favorably with outcomes of historical control series. We agree that adjuvant hormonal therapy is also an integral part of optimal management of selected patients with LABC (those >50 years old, and with estrogen receptor-positive tumors). The world overview demonstrated an additive effect in women treated with both systemic modalities. Therefore, for this high-risk group of patients, combined hormone and chemotherapy for those who present with hormone-responsive breast cancer might be the treatment of choice. On the other hand, the role of neoadjuvant hormonal therapy alone remains to be defined. When we last reviewed this issue [5], only limited data were available, and the results did not appear superior to local treatments without systemic therapy. We (and others) are prospectively assessing the role of neoadjuvant tamoxifen in selected patients with LABC (those who are elderly and those patients unfit for chemotherapy). Professor Oliver's comments about other important areas in breast cancer research were beyond the scope of our review.}, } @article {pmid9084285, year = {1996}, author = {Hildebolt, CF and Walkup, RK and Conover, GL and Yokoyama-Crothers, N and Bartlett, TQ and Vannier, MW and Shrout, MK and Camp, JJ}, title = {Histogram-matching and histogram-flattening contrast correction methods: a comparison.}, journal = {Dento maxillo facial radiology}, volume = {25}, number = {1}, pages = {42-47}, doi = {10.1259/dmfr.25.1.9084285}, pmid = {9084285}, issn = {0250-832X}, support = {DE08173/DE09861/DE/NIDCR NIH HHS/United States ; }, mesh = {*Algorithms ; Radiographic Image Enhancement/*methods ; *Radiography, Dental ; Signal Processing, Computer-Assisted ; *Subtraction Technique ; }, abstract = {OBJECTIVES: To compare the results or two methods of histogram matching and two methods of histogram flattening for their ability to correct for contrast variations in digital dental images.

METHODS: A custom-built, aluminium stepwedge with 0.1, 0.5 and 1.0 mm steps was placed over Ektaspeed films and exposed for 0.06, 0.12 and 0.25 s, respectively. Radiographs were digitized at 50 microns spatial resolution and 12-bit contrast resolution. Contrast corrections were performed using Rüttimann et al.'s algorithm (1986) for one method of matching (RM) and flattening (RF) and Castleman's algorithm (1979) for the other method of matching (CM) and flattening (CF). Mean pixel grey-scale values were determined for each step. The 0.12 s exposure was considered to be the target image exposure. Absolute differences in pixel grey-scale values between the target images and the modified images were determined.

RESULTS: The median values of the absolute differences in pixel grey-scale values between the target images and the contrast corrected images were: CM = 4.3; RM = 4.1; CF = 70.2 and RF = 70.2.

CONCLUSION: Castleman's and Rüttimann's matching algorithms perform equally well in correcting digital image contrast. Histogram flattening was less effective.}, } @article {pmid8805085, year = {1996}, author = {Fingerman, KL and Gallagher-Thompson, D and Lovett, S and Rose, J}, title = {Internal resourcefulness, task demands, coping, and dysphoric affect among caregivers of the frail elderly.}, journal = {International journal of aging & human development}, volume = {42}, number = {3}, pages = {229-248}, doi = {10.2190/UHJB-CA5L-2K03-3BNV}, pmid = {8805085}, issn = {0091-4150}, support = {AGO4572/AG/NIA NIH HHS/United States ; }, mesh = {*Adaptation, Psychological ; Adult ; Aged ; Caregivers/*psychology ; Defense Mechanisms ; Depression/*psychology ; Female ; Follow-Up Studies ; Frail Elderly/*psychology ; Humans ; *Internal-External Control ; Male ; Middle Aged ; Personality Inventory ; *Workload ; }, abstract = {Internal resourcefulness is defined as the repertoire of skills and behaviors individuals employ to deal with negative affective states. The relationships among caregivers' internal resourcefulness, demands of the caregiving situation, and caregivers' self-reported coping behaviors were examined relative to changes in dysphoric affect over time. Primary caregivers of the frail elderly (N = 143) completed the following measures, at two time periods, approximately four months apart: Rosenbaum's Self Control Schedule, assessing internal resourcefulness; Poulshock and Deimling's list of tasks carried out for the frail elder; Zarit et al.'s Memory and Behavior Problem Check List assessing caregiver burden; Moos et al.'s Indices of Coping; and Beck et al.'s Depression Inventory as a means of assessing dysphoric affect. Although caregivers' reactions to the care recipients' annoying behaviors predicted negative affect at time 1 and avoidant coping behavior predicted negative affect at times 1 and 2, internal resourcefulness was the only significant predictor of changes in dysphoric affect over time. Decreased dysphoric affect among caregivers was linked to possession of a larger initial set of internal resources to deal with negative internal experiences.}, } @article {pmid8805083, year = {1996}, author = {Peterson, CC}, title = {The ticking of the social clock: adults' beliefs about the timing of transition events.}, journal = {International journal of aging & human development}, volume = {42}, number = {3}, pages = {189-203}, doi = {10.2190/MMDD-F9YP-NPN8-720M}, pmid = {8805083}, issn = {0091-4150}, mesh = {Adolescent ; Adult ; Aged ; Aging/*psychology ; Female ; Gender Identity ; Humans ; *Life Change Events ; Male ; Middle Aged ; Parenting ; Retirement/psychology ; Self Concept ; Social Values ; Stereotyping ; Students/psychology ; }, abstract = {In two studies, beliefs about descriptive and prescriptive age norms for adult developmental transitions were examined in a sample of 214 Australian university students aged seventeen to fifty years. The results of Study 1 revealed a belief by the vast majority that descriptive age norms still exist for both family transitions (marriage, parenthood, grandparenthood) and career transitions (leaving school, retirement). While these results were in keeping with those of Neugarten et al.'s original study of age norms in the United States, the actual "best" normative ages recommended by this sample of contemporary Australian adults differed in every case from the U.S. age norms of three decades ago. Matching contemporary demographic trends, the present Australian young-adult sample advocated later ages for marriage and grandparenthood, a younger norm for leaving school, and a broader normative age range for retiring from work. Study 2 tested Neugarten's hypothesis that age norms today lack some of the prescriptive overtones implicit in original "social clock" concept. The results supported this suggestion. In fact, only a minority of contemporary Australian adults believed that there were prescriptive upper age boundaries for first marriage or university study. Furthermore, their prescriptive lower age limits for every transition except retirement fell at or below the onset of adulthood itself (18 years), in keeping with biological constraints on procreation and maturational constraints on social and cognitive development. The mean ranges of acceptability prescribed by this Australian sample for each key adult transition were likewise very wide, stretching from an average of twenty-four years (for motherhood) to forty-nine years (for a man's first marriage). This result also contrasts sharply with the ranges of no more than five years prescribed for the same transitions by the vast majority of Neugarten et al.'s sample three decade ago. The probable consequences for self-esteem, mental health and life planning of this heightened variability and reduced prescriptiveness in the timing of life events for contemporary men and women were discussed.}, } @article {pmid8712162, year = {1996}, author = {Kumar, VK and Marcano, G and Pekala, RJ}, title = {Behavioral and subjective scoring of the Harvard Group Scale of Hypnotic Susceptibility: further data and an extension.}, journal = {The American journal of clinical hypnosis}, volume = {38}, number = {3}, pages = {191-199}, doi = {10.1080/00029157.1996.10403337}, pmid = {8712162}, issn = {0002-9157}, mesh = {Adult ; Female ; Humans ; *Hypnosis ; Male ; Personality Inventory/*statistics & numerical data ; Psychometrics ; Reproducibility of Results ; *Suggestion ; }, abstract = {The present study replicated and extended Kirsch, Council, and Wickless's work evaluating the reliability and concurrent validity of a subjective response scale developed for the Harvard Group Scale of Hypnotic Susceptibility. Consistent with Kirsch et al.'s findings, the subjective counterpart of the Harvard scale demonstrated high reliability (coefficient .90) and concurrent validity (r = .84 with Harvard's standard behavioral score). Similar correlations of the behavioral and subjective scales with the Dissociative Experience Scale (DES) and Phenomenology of Consciousness Inventory (PCI) suggested that the two hypnotizability scales are measuring similar constructs. However, using the two scales in combination did not yield a morestringent measure of hypnotizability in terms of DES and PCI variables than using either of them alone.}, } @article {pmid8693049, year = {1996}, author = {Hubbard, TL}, title = {Displacement in depth: representational momentum and boundary extension.}, journal = {Psychological research}, volume = {59}, number = {1}, pages = {33-47}, pmid = {8693049}, issn = {0340-0727}, mesh = {Acceleration ; Adult ; *Depth Perception ; Female ; Humans ; Male ; *Mental Recall ; *Motion Perception ; Optical Illusions ; *Orientation ; Pattern Recognition, Visual ; Psychophysics ; Retention, Psychology ; }, abstract = {Memory for targets moving in depth and for stationary targets was examined in five experiments. Memory for targets moving in depth was displaced behind the target with slower target velocities (longer ISIs and retention intervals) and beyond the target with faster target velocities (shorter ISIs and retention intervals), and the overall magnitude of forward displacement for motion in depth was less than the overall magnitude of forward displacement for motion in the picture plane. Memory for stationary targets was initially displaced away from the observer, but memory for smaller stationary targets was subsequently displaced toward the observer and memory for larger stationary targets was subsequently displaced away from the observer; memory for the top or bottom edge of a stationary target was displaced inside the target perimeter. The data are consistent with Freyd and Johnson's (1987) two-component model of the time course of representational momentum and with Intraub et al.'s (1992) two-component model of boundary extension.}, } @article {pmid9183990, year = {1995}, author = {Prinzel, LJ and Freeman, FG}, title = {Sex differences in visuo-spatial ability: task difficulty, speed-accuracy tradeoff, and other performance factors.}, journal = {Canadian journal of experimental psychology = Revue canadienne de psychologie experimentale}, volume = {49}, number = {4}, pages = {530-539}, doi = {10.1037/1196-1961.49.4.530}, pmid = {9183990}, issn = {1196-1961}, mesh = {Adolescent ; Adult ; Female ; Humans ; Male ; Mental Processes ; Sex Factors ; *Spatial Behavior ; Task Performance and Analysis ; *Visual Perception ; }, abstract = {Males have consistently been found to perform better than females on a task that requires the subject to mentally rotate a figure. Recently, Goldstein. Haldane, and Mitchell (1990) suggested that performance factors are operative in explaining sex differences in spatial ability. However, Stumpf (1993) was unable to replicate all of Goldstein et al.'s (1990) findings and to generalize them to other measures of spatial ability. In this study, it was hypothesized (1) that females would take longer to respond and would get fewer correct items than males on a spatial rotation task, and (2) that only females would show a speed-accuracy tradeoff as the difficulty of the spatial task increased from the 90 degrees to 180 degrees rotated conditions. The results confirmed each of these hypotheses. Furthermore, as Stumpf (1993) found, when ratio scores from the number of items correct to number attempted were computed for both males and females, differences in spatial ability were reduced, though still evident.}, } @article {pmid8600585, year = {1995}, author = {Blecher, MS and Steinberg, M and Pick, W and Hennink, M and Durcan, N}, title = {AIDS--knowledge, attitudes and practices among STD clinic attenders in the Cape Peninsula.}, journal = {South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde}, volume = {85}, number = {12}, pages = {1281-1286}, pmid = {8600585}, issn = {0256-9574}, mesh = {Acquired Immunodeficiency Syndrome/*prevention & control ; Adult ; Female ; *Health Knowledge, Attitudes, Practice ; Humans ; Male ; Patient Education as Topic ; Risk Factors ; Sexual Behavior ; Sexually Transmitted Diseases/*psychology ; South Africa ; Surveys and Questionnaires ; }, abstract = {This study aimed to determine knowledge about, attitudes to and practices associated with AIDS among sexually transmitted disease (STD) clinic attenders in the Cape Peninsula. A questionnaire containing open and closed questions in the appropriate language (English, Afrikaans or Xhosa) was administered by trained clinic staff to 306 patients in 9 of the 29 STD clinics in the region. The median age of attenders was 25 years. The median period of residence in the peninsula was 7 years. There was inadequate awareness of the asymptomatic carrier state, the incurability of AIDS and ways to prevent AIDS. Sexual practice was a high risk: 70.4% of male attenders reported 2 or more partners since the beginning of the year (average 9 months); 39.5% of men reported more than one episode of STD in the previous 2 years. Prostitution was perceived to be common in attenders' communities. There was a low perception of risk to self, and intention to change behaviour was low. More information about AIDS was requested by 98% of patients. These findings are discussed with reference to the health belief model, Fischbein and Ajzen's theory of reasoned action and Catania et al.'s AIDS risk reduction model. This study supports the urgent need for AIDS education and counselling programmes for patients with STDs in the region. Recommendations include the need to address the beliefs and attitudes that affect behaviour, as well as to convey knowledge.}, } @article {pmid8599378, year = {1995}, author = {Merriwether, DA and Rothhammer, F and Ferrell, RE}, title = {Distribution of the four founding lineage haplotypes in Native Americans suggests a single wave of migration for the New World.}, journal = {American journal of physical anthropology}, volume = {98}, number = {4}, pages = {411-430}, doi = {10.1002/ajpa.1330980404}, pmid = {8599378}, issn = {0002-9483}, support = {P41 RR06009/RR/NCRR NIH HHS/United States ; }, mesh = {Americas/ethnology ; DNA, Mitochondrial/*genetics ; *Emigration and Immigration ; Female ; Gene Deletion ; Genetic Variation ; Genetics, Population ; *Haplotypes ; Humans ; Indians, Central American/*genetics ; Indians, North American/*genetics ; Indians, South American/*genetics ; Male ; }, abstract = {The distribution of the four founding lineage haplogroups in Native Americans from North, Central, and South America shows a north to south increase in the frequency of lineage B and a North to South decrease in the frequency of lineage A. All four founding lineage haplogroups were detected in North, Central, and South America, and in Greenberg et al.'s ([1986] Curr. Anthropol. 27:477-497) three major linguistic groups (Amerind, NaDene, and Eskaleut), with all four haplogroups often found within a single population. Lineage A was the most common lineage in North America, regardless of language group. This overall distribution is most parsimonious with a single wave of migration into the New World which included multiple variants of all four founding lineage types. Torroni et al.'s ([1993a] Am. J. Hum. Genet. 53:563-590) report that lineage B has a more recent divergence time than the other three lineages can best be explained by multiple variants of lineages A, C, and D, and fewer variants of lineage B entering the New World. Alternatively, there could have been multiple waves of migration from a single parent population in Asia/Siberia which repeatedly reintroduced the same lineages to the New World.}, } @article {pmid8524916, year = {1995}, author = {Burrows, R and Hofer, H and East, ML}, title = {Population dynamics, intervention and survival in African wild dogs (Lycaon pictus).}, journal = {Proceedings. Biological sciences}, volume = {262}, number = {1364}, pages = {235-245}, doi = {10.1098/rspb.1995.0201}, pmid = {8524916}, issn = {0962-8452}, mesh = {Animals ; Animals, Wild/*physiology/psychology ; Dogs ; Handling, Psychological ; Population Dynamics ; Stress, Psychological ; }, abstract = {The demography of Serengeti wild dog study packs and their extinction in 1991 was documented by Burrows et al. (1994). One explanation for pack loss compatible with demographic evidence was viral disease induced by stress caused by intervention (vaccination, immobilization and radio-collaring). Several studies claim to reject this hypothesis. However, cortisol levels measured in immobilized Lycaon, whose pathogen exposure is unknown, do not demonstrate that interventions in the Serengeti were benign. The analysis of survivorship in Lycaon in other ecosystems minimized the chance of demonstrating any effect of intervention and failed to consider vaccinations as intervention. There is now evidence that intervention significantly decreased survivorship of Masai Mara Lycaon. Further simulations of the likelihood of population extinction in Serengeti Lycaon, evidence of limited population variability and a small scaling factor in Serengeti Lycaon strengthen Burrows et al.'s conclusion that the extinction was unlikely to be due to chance alone. Although some studies claim that Lycaon conservation is doomed without intervention, to date vaccinations, blood sampling and radio-telemetry have contributed little to Lycaon conservation. All studies fail to disprove the Burrows hypothesis or provide convincing alternatives.}, } @article {pmid8600278, year = {1995}, author = {Vuhahula, EA and Nikai, H and Ogawa, I and Miyauchi, M and Takata, T and Ito, H and Ito, R}, title = {Correlation between argyrophilic nucleolar organizer region (AgNOR) counts and histologic grades with respect to biologic behavior of salivary adenoid cystic carcinoma.}, journal = {Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology}, volume = {24}, number = {10}, pages = {437-442}, doi = {10.1111/j.1600-0714.1995.tb01130.x}, pmid = {8600278}, issn = {0904-2512}, mesh = {Adult ; Aged ; Aged, 80 and over ; Carcinoma, Adenoid Cystic/*pathology/secondary/ultrastructure ; *Coloring Agents ; Disease-Free Survival ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Neoplasm Recurrence, Local/pathology ; Nucleolus Organizer Region/*ultrastructure ; Prognosis ; Salivary Gland Neoplasms/*pathology/ultrastructure ; Salivary Glands, Minor/pathology ; *Silver ; Survival Rate ; }, abstract = {The quantification of argyrophilic nucleolar organizer regions (AgNOR) was performed in 34 cases of adenoid cystic carcinoma (ACC) to determine (1) whether AgNOR count correlates with its different histologic grades pertinent to prognosis, and (2) whether AgNOR counts can offer any additional prognostic advantage over histologic grading. According to Szanto et al.'s histologic grading criteria (4), 12 cases were Grade 1, 7 cases Grade 2, and 15 were Grade 3. Patients were divided into 20 favorable cases (without metastases) and 14 unfavorable cases (with metastases). Although most Grade 3 tumors had high AgNOR counts (> or = 4) and Grade 1 tumors with low (< 4) AgNOR counts outnumbered those with high AgNOR counts, considerable overlap of AgNOR values in different grades was observed. However, all unfavorable cases had high AgNOR counts regardless of their histologic grades, suggesting that the metabolic alterations associated with the malignancy level of ACC may partly be portrayed by the AgNOR count, irrespective of the histologic appearance. Cumulative survival rates of Grade 1 tumors and of tumors with low AgNOR counts were better than those of Grade 3 tumors and those with high AgNOR counts. Within the limited number of cases in this series the AgNOR count exhibits a potential for identifying some aggressive ACCs that cannot be detected by histology alone.}, } @article {pmid8573330, year = {1995}, author = {Noël, MP and Seron, X}, title = {Lexicalization errors in writing arabic numerals: a single-case study.}, journal = {Brain and cognition}, volume = {29}, number = {2}, pages = {151-179}, doi = {10.1006/brcg.1995.1274}, pmid = {8573330}, issn = {0278-2626}, mesh = {Aged ; Apraxias/diagnosis/psychology ; Cognition Disorders/*diagnosis/psychology ; Dementia/*diagnosis/psychology ; Humans ; Language Disorders/*diagnosis/psychology ; Male ; Models, Psychological ; Neuropsychological Tests ; Psychiatric Status Rating Scales ; Semantics ; }, abstract = {This paper presents a single-case study of a patient suffering from several impairments in number processing. The main focus of the paper is to describe and interpret the patient's errors in verbal to arabic transcoding. The errors were of the syntactical type and consisted of partial lexicalizations appearing mainly in response to items with Thousand in sum relationships and less frequently with Hundred in sum relationships. The Discussion section compares three models in their ability to account for the patient's dissociation. It was suggested that models such as that of McCloskey, Caramazza, and Basili (1985), postulating a semantic representation for numbers built up on a base-ten system, are unable to account for the patient's errors. By contrast, Power et al.'s perspective (Power & Longuet-Higgins, 1978; Power & Dal Martello, 1990), which posits a semantic representation of numbers reflecting the structure of the verbal numeral system, could provide an economical interpretation for the dissociation observed between the mastery of sum and product relationships. Similarly, the asemantic transcoding model developed by Deloche and Seron (1987) gives a valid account for the patient's profile.}, } @article {pmid8554771, year = {1995}, author = {Fuchs, C and Benson, BA}, title = {Social information processing by aggressive and nonaggressive men with mental retardation.}, journal = {American journal of mental retardation : AJMR}, volume = {100}, number = {3}, pages = {244-252}, pmid = {8554771}, issn = {0895-8017}, mesh = {Aggression/*psychology ; Cognition Disorders/etiology/*psychology ; Conflict, Psychological ; Humans ; Intellectual Disability/complications/*psychology ; Male ; Problem Solving ; }, abstract = {The social information-processing skills of 16 aggressive and 19 nonaggressive men with borderline to moderate mental retardation were examined in light of some of the steps described in Dodge's social information-processing model (Dodge, Pettit, McClaskey, & Brown, 1986). Contrary to expectations based on Dodge et al.'s findings with children who did not have mental retardation, aggressive and nonaggressive groups did not differ in their ability to generate multiple solutions or in their ability to provide appropriate responses. Similar to Dodge et al.'s findings, however, subjects in the aggressive group generated significantly more aggressive solutions and tended more often to give an aggressive response first than did the nonaggressive subjects. Preliminary implication for treatment were offered.}, } @article {pmid7490577, year = {1995}, author = {Lea, RB}, title = {On-line evidence for elaborative logical inferences in text.}, journal = {Journal of experimental psychology. Learning, memory, and cognition}, volume = {21}, number = {6}, pages = {1469-1482}, doi = {10.1037//0278-7393.21.6.1469}, pmid = {7490577}, issn = {0278-7393}, support = {MH 16745/MH/NIMH NIH HHS/United States ; }, mesh = {Form Perception/*physiology ; Humans ; *Logic ; Memory/*physiology ; Models, Psychological ; *Reading ; }, abstract = {A model of propositional-logic reasoning proposed by M. D. S. Braine, B. J. Reiser, and B. Rumain (1984) claims that inferences such as "p or q; not p/therefore q" are made spontaneously by readers at the moment both premises are available. This claim is inconsistent with some evidence in the text-processing literature that suggests that only those inferences necessary for textual coherence are made spontaneously. In the present study, participants read stories in which a logical inference was not necessary to maintain textual coherence, and inference making was assessed with on-line probes. Two experiments tested logical forms central to Braine et al.'s model, and both indicated that participants were making the logical inferences. Two further experiments replicated this result with stories that did not begin with thematic titles. These findings support Braine et al.'s prediction that some propositional-logic inferences are made routinely in texts that do not require them for coherence.}, } @article {pmid8557887, year = {1995}, author = {Nelson, EC and Cloninger, CR}, title = {The tridimensional personality questionnaire as a predictor of response to nefazodone treatment of depression.}, journal = {Journal of affective disorders}, volume = {35}, number = {1-2}, pages = {51-57}, doi = {10.1016/0165-0327(95)00038-o}, pmid = {8557887}, issn = {0165-0327}, mesh = {Adult ; Antidepressive Agents/adverse effects/*therapeutic use ; Depressive Disorder/*drug therapy/psychology ; Dose-Response Relationship, Drug ; Drug Administration Schedule ; Female ; Humans ; Male ; Obsessive-Compulsive Disorder/drug therapy/psychology ; Personality Development ; *Personality Inventory/statistics & numerical data ; Piperazines ; Prognosis ; Psychometrics ; Regression Analysis ; Triazoles/adverse effects/*therapeutic use ; }, abstract = {Personality traits have emerged as the strongest identified predictors of response to antidepressant treatment of major depressive disorder (Peselow et al., 1992; Joyce et al., 1994). 18 subjects in the midst of a major depressive episode were treated with nefazodone in an open trial. All subjects completed Cloninger's tridimensional personality questionnaire (TPQ) before beginning treatment. A multiple regression analysis was performed in an attempt to replicate Joyce et al.'s (1994) finding that temperament type, as assessed by the TPQ, is a strong predictor of antidepressant response. A model involving TPQ reward dependence and harm avoidance scores, and their interaction, was found to significantly predict the response to nefazodone (r2 = 0.47, P < 0.027). When response was defined as a 50% decrease in HAM-D score at last visit, high reward dependence score alone significantly separated responders from nonresponders (Fisher's exact P = 0.050, df = 1). These results raise the intriguing possibility that TPQ scores may have direct clinical applications.}, } @article {pmid8555712, year = {1995}, author = {Griffiths, P and Paterson, L and Harvie, A}, title = {Neuropsychological effects of subsequent exposure to phenylalanine in adolescents and young adults with early-treated phenylketonuria.}, journal = {Journal of intellectual disability research : JIDR}, volume = {39 (Pt 5)}, number = {}, pages = {365-372}, doi = {10.1111/j.1365-2788.1995.tb00540.x}, pmid = {8555712}, issn = {0964-2633}, mesh = {Adolescent ; Adult ; Brain Damage, Chronic/*diagnosis/prevention & control/psychology ; Child ; Female ; Follow-Up Studies ; Humans ; Intellectual Disability/diagnosis/diet therapy/psychology ; Male ; *Neuropsychological Tests ; Phenylalanine/administration & dosage/*adverse effects/blood ; Phenylketonurias/*diagnosis/diet therapy/psychology ; Scotland ; }, abstract = {Severe mental handicap in phenylketonuria (PKU) can be prevented if dietary treatment is implemented at birth. Controversy remains about the optimum age for terminating treatment. A group of adolescents and young adults with PKU from the West of Scotland Register was identified which had received early treatment, been well-controlled on diet, ceased treatment at 10 years old and subsequently were hyperphenylalaninaemic for 3 years or more. They were given a battery of neuropsychological tests and their results were compared with those of on-diet subjects with PKU and normal controls. The findings generally supported the view that dietary cessation at age 10 is sufficient to prevent a substantial reduction of cognitive and motor ability, and that the central nervous system is probably mature enough to withstand the toxic effects of high blood phenylalanine by then. However, there were minor indications, in keeping with Welsh et al.'s hypothesis [M.C. Welsh, B.F. Pennington, S. Ozonoff, B. Rouse & E.R.B. McCabe (1990) Neuropsychology of early-treated phenylketonuria: specific executive function deficits.}, } @article {pmid8845784, year = {1995}, author = {Norman, P}, title = {Applying the health belief model to the prediction of attendance at health checks in general practice.}, journal = {The British journal of clinical psychology}, volume = {34}, number = {3}, pages = {461-470}, doi = {10.1111/j.2044-8260.1995.tb01480.x}, pmid = {8845784}, issn = {0144-6657}, mesh = {Adult ; *Attention ; *Culture ; *Health Behavior ; *Health Status ; Humans ; Models, Psychological ; Statistics as Topic ; Surveys and Questionnaires ; }, abstract = {This paper reports a prospective study which sought to assess the role of the health belief model (HBM) in predicting attendance at health checks in general practice. Conducted in a single practice, 299 patients were invited to attend a health check. These patients were sent invitation letters containing either an appointment or an open invitation. The results first showed that the sending of appointment letters led to a higher attendance rate (59.2 vs. 26.5 percent). Second, when the predictors of attendance behaviour were considered it was found that, compared with non-attenders, those who attended in response to an appointment letter were more likely to have intended to attend while those who attended in response to an open letter were more likely to have placed a high value on their health. These results are consistent with Marteau et al.'s (1992) claim that attendance at screening should be viewed as a heterogeneous behaviour, such that the health beliefs which distinguish attenders from non-attenders should be seen to vary according to the way in which patients are invited.}, } @article {pmid8590096, year = {1995}, author = {Su, H and Silversides, FG and Villeneuve, P}, title = {Ovarian morphology and follicular development in sex-linked imperfect albino (s(al)-s) and nonalbino hens before or after a forced moult.}, journal = {British poultry science}, volume = {36}, number = {4}, pages = {645-653}, doi = {10.1080/00071669508417809}, pmid = {8590096}, issn = {0007-1668}, mesh = {Albinism/genetics/pathology/*veterinary ; Animals ; *Chickens/anatomy & histology/genetics/physiology ; Female ; *Genetic Linkage ; Genotype ; Organ Size ; Ovarian Follicle/*physiology ; Ovary/anatomy & histology ; Oviducts/anatomy & histology ; Oviposition ; Poultry Diseases/*genetics/pathology/physiopathology ; Statistics as Topic ; *X Chromosome ; }, abstract = {1. The effects of the s(al-s) gene on ovarian morphology and the development of ovarian follicles in old laying hens before and after a forced moult were investigated by measuring and weighing the ovaries and follicles. 2. The laying rate of albinos was higher than that of nonalbinos before the forced moult but not afterwards. Hierarchical follicles in albino hens were smaller than those of nonalbinos before but not after the moult. 3. Growth intensity of hierarchical follicles was greater in albino hens before the moult, suggesting that follicular maturation was more rapid, possibly explaining the higher egg production observed. 4. All differences between genotypes disappeared after the moult, suggesting that the state of the ovary before a moult is independent of that afterwards.}, } @article {pmid8541136, year = {1995}, author = {Puche, RC and Morosano, M and Masoni, A and Perez Jimeno, N and Bertoluzzo, SM and Podadera, JC and Podadera, MA and Bocanera, R and Tozzini, R}, title = {The natural history of kyphosis in postmenopausal women.}, journal = {Bone}, volume = {17}, number = {3}, pages = {239-246}, doi = {10.1016/8756-3282(95)00212-v}, pmid = {8541136}, issn = {8756-3282}, mesh = {Adult ; Aged ; Aged, 80 and over ; Aging ; Bone Density ; Bone Remodeling ; Calcium, Dietary/administration & dosage ; Cross-Sectional Studies ; Female ; Humans ; Kyphosis/*etiology ; Middle Aged ; Postmenopause/*physiology ; Retrospective Studies ; Spinal Fractures/complications ; Thoracic Vertebrae/injuries/pathology ; }, abstract = {A cross-sectional study of vertebral morphometry in 449 unscreened postmenopausal women, from the ages of 40 to 80, is reported. The wedge angles of thoracic vertebrae T4-12 were found to increase exponentially as a function of age, up to 70 years. In addition to age, the wedging phenomenon was found to be accentuated by increased bone turnover due to low calcium intake, reduced physical activity, each successive delivery, and breast feeding. Most of these variables were not correlated with isolated vertebral wedge angles, but rather with the sum of them (Sigma, sigma), assumed to assess the impact of those variables on thoracic kyphosis. In a subset of women, sigma was found to be inversely correlated with low spinal mineral density at L2-4. T-11 and T-12 were the vertebrae most frequently deformed (wedge angle exceeding mean +/- 3 SD in a group of 50 young healthy women, 25-45 years old). The distribution of deformed vertebrae was found to be significantly different from those qualified as "fractured" according to Kleerekoper et al.'s (1984) and Melton et al.'s (1989) criteria. The overall information afforded by past and present data indicates that in postmenopausal women, vertebral deformation may occur with the help of mechanical solicitations plus high bone remodeling rates, as well as by structural collapse (fracture). The information obtained does not allow one to quantify the relative contribution of each set of factors to the wedging phenomenon.}, } @article {pmid7657937, year = {1995}, author = {Cohen-Mansfield, J and Werner, P and Reisberg, B}, title = {Temporal order of cognitive and functional loss in a nursing home population.}, journal = {Journal of the American Geriatrics Society}, volume = {43}, number = {9}, pages = {974-978}, doi = {10.1111/j.1532-5415.1995.tb05560.x}, pmid = {7657937}, issn = {0002-8614}, support = {AG08675/AG/NIA NIH HHS/United States ; K01 AG00547/AG/NIA NIH HHS/United States ; }, mesh = {*Activities of Daily Living ; Aged ; Aged, 80 and over ; *Cognition Disorders ; Female ; *Homes for the Aged ; Humans ; Male ; Memory ; *Nursing Homes ; Time Factors ; }, abstract = {OBJECTIVE: The order in which cognition and the ability to perform activities of daily living (ADLs) are lost in an institutionalized aged population was examined. Understanding the order of loss of function is important for preparing caregivers and planning of care.

METHOD: The conditional probabilities of the inability to perform activity A when there exists the inability to perform activity B were explored in secondary analyses of cross-sectional data describing 408 nursing home residents. Residents' abilities to perform ADLs were rated by nursing staff using Linn and Linn's Rapid Disability Rating Scale (RDRS-2); cognitive functioning was rated by social workers and nursing staff using a modified version of Reisberg et al.'s Brief Cognitive Rating Scale (BCRS, with 4 axes: orientation, concentration, recent memory, and past memory).

RESULTS: The results regarding ADLs confirm previous findings of a natural order of loss of ability (from the one lost first to last): bathing, dressing, grooming, toileting, walking, and eating. The examination of order in the loss of concentration, recent memory, past memory, and orientation revealed that these seem to be lost concurrently when the cutpoint was 3 (i.e., relatively normal functioning vs. moderate and severe dementia). When the cutpoint was 6 (i.e., severe dementia vs. higher levels of functioning), the order that emerged was: recent memory, past memory, concentration, and orientation.

CONCLUSIONS: Although there is a significant relationship between loss of ability to perform ADLs and stage of cognitive impairment, the loss of any specific ADL is not uniquely related to any one stage of cognitive deterioration in this diverse population. This may be explained by the high prevalence of disease in this institutionalized population, as exemplified by the 60% suffering from arthritis and the 17% suffering from neurological disorders other than dementia.}, } @article {pmid7656074, year = {1995}, author = {Pruchno, RA and Peters, ND and Burant, CJ}, title = {Mental health of coresident family caregivers: examination of a two-factor model.}, journal = {The journals of gerontology. Series B, Psychological sciences and social sciences}, volume = {50}, number = {5}, pages = {P247-56}, doi = {10.1093/geronb/50b.5.p247}, pmid = {7656074}, issn = {1079-5014}, support = {P01 MH43371/MH/NIMH NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Affect ; Aged ; Behavior ; Caregivers/*psychology ; Child ; Depression/etiology ; Family/psychology ; Female ; Health Status ; Humans ; Male ; *Mental Health ; Middle Aged ; Models, Psychological ; Personal Satisfaction ; Spouses/psychology ; }, abstract = {Data were collected from 140 caregivers of elderly relatives, their husbands, and coresident children. Lawton et al.'s (1991) parallel channel hypothesis, which suggests that positive and negative aspects of mental health have differential predictors, was tested. Data from caregivers, their husbands, and children support the hypothesized model, with greater interdependence of psychological process being associated with greater role centrality.}, } @article {pmid7551776, year = {1995}, author = {Slugoski, BR}, title = {Mindless processing of requests? Don't ask twice.}, journal = {The British journal of social psychology}, volume = {34 (Pt 3)}, number = {}, pages = {335-350}, doi = {10.1111/j.2044-8309.1995.tb01068.x}, pmid = {7551776}, issn = {0144-6665}, mesh = {Adult ; *Attention ; Attitude ; *Cooperative Behavior ; Female ; Humans ; *Interpersonal Relations ; Male ; *Mental Recall ; Social Values ; *Speech Perception ; }, abstract = {This study examines the mindlessness hypothesis and its associated compliance-gaining paradigm from the perspective of politeness theory. The main prediction of politeness theory, which is not taken into account in the mindlessness literature, is that the perceived magnitude of an imposition is a function not only of the size of favour asked but also of the framing of the request itself. A confederate asked students studying in the library for either one or 10 sheets of paper using appropriate variations of Langer et al.'s three request types: no reason, placebic reason and real reason. Students then completed a questionnaire to determine: (a) how large the imposition on them had been; (b) their verbatim memories for the requests; and (c) self-reported compliance with the requests. In order to examine the effect of reflective thought on subjects' judgements and recall, this questionnaire was completed either immediately following compliance/non-compliance or three minutes later. The analyses established that the perceived imposition is influenced jointly by the actual imposition, the type of request and the time of judgement. Further, contrary to some previous research, the recall memory data provide support for a strong version of the mindlessness hypothesis, as well as new evidence for the reconstructive character of conversation memory. It is concluded that politeness theory describes a powerful heuristic that people use when processing requests.}, } @article {pmid7577764, year = {1995}, author = {Baum, KM and Walker, EF}, title = {Childhood behavioral precursors of adult symptom dimensions in schizophrenia.}, journal = {Schizophrenia research}, volume = {16}, number = {2}, pages = {111-120}, doi = {10.1016/0920-9964(94)00071-f}, pmid = {7577764}, issn = {0920-9964}, support = {MH00876/MH/NIMH NIH HHS/United States ; MH46496/MH/NIMH NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Child ; Child Behavior Disorders/*diagnosis/psychology ; Child, Preschool ; Cognition Disorders/diagnosis/psychology ; Female ; Humans ; Infant ; Infant, Newborn ; Male ; Middle Aged ; Perceptual Distortion ; Personality Assessment ; Personality Development ; Psychiatric Status Rating Scales ; Psychomotor Disorders/diagnosis/psychology ; Reality Testing ; Schizotypal Personality Disorder/*diagnosis/psychology ; }, abstract = {The present investigation tested the hypothesis that childhood behavioral problems are differentially associated with clinical symptoms in adult-onset schizophrenia. Parents of 29 schizophrenic patients completed questionnaires concerning (1) the childhood behaviors of all their offspring from birth through 15 years of age, and (2) the symptomatology of their schizophrenic offspring. The childhood behavior scale was a modified version of Achenbach's Child Behavior Checklist (1991). Scores were derived for six childhood behavior problem factors: Withdrawal, Anxiety/Depression, Social Problems, Thought Problems, Attention Problems, and Aggression/Delinquency. Ratings of symptoms were based on parental versions of Andreasen's Scale for the Assessment of Positive Symptoms (SAPS; 1983) and Scale for the Assessment of Negative Symptoms (SANS; 1981). Symptomatology scores were computed from the SANS and SAPS following Malla et al.'s (1993) and Liddle's (1987b) tri-dimensional concept of schizophrenia: Reality Distortion, Psychomotor Poverty and Cognitive Disorganization. Regression analyses were conducted to examine the relation between childhood behavior and adult symptomatology in the schizophrenic patients. The results indicated that the Psychomotor Poverty and Cognitive Disorganization dimensions in adult patients are positively associated with Withdrawn behavior and inversely associated with Anxious/Depressed characteristics in childhood. The results are discussed in light of the distinction between primary and secondary negative symptoms, and the three dimension concept of schizophrenia.}, } @article {pmid8550732, year = {1995}, author = {Marcus, GF}, title = {Children's overregularization of English plurals: a quantitative analysis.}, journal = {Journal of child language}, volume = {22}, number = {2}, pages = {447-459}, doi = {10.1017/s0305000900009879}, pmid = {8550732}, issn = {0305-0009}, support = {HD 18381/HD/NICHD NIH HHS/United States ; T32 MH18823/MH/NIMH NIH HHS/United States ; }, mesh = {Child Language ; Child, Preschool ; Humans ; Language ; Language Development ; *Verbal Learning ; }, abstract = {This paper brings a quantitative study of children's noun plural overregularizations (foots, mans) to bear on recent comparisons of connectionist and symbolic models of language. The speech of 10 English-speaking children (aged 1;3 to 5;2) from the CHILDES database (MacWhinney & Snow, 1985, 1990) were analysed. The rate of noun overregularization is low, mean = 8.5%, demonstrating that children prefer correct to overregularized forms. Rates of noun overregularization are not significantly different from their rates of past tense overregularization, and noun plurals, like verb past tenses, follow a U-shaped developmental curve in which correct irregulars precede the first overregularized forms. These facts suggest that plural and past tense overregularizations are caused by similar underlying processes. The results pose challenges to connectionist models, but are consistent with Marcus et al.'s (1992) blocking-and-retrieval-failure model in which regulars are generated by a default rule while irregulars are retrieved from the lexicon.}, } @article {pmid8522222, year = {1995}, author = {Jendryczko, A and Tomala, J and Szpyrka, G and Kossowski, P and Kozowicz, M}, title = {[Mineral components of the human placenta, birth weight and infant head circumference].}, journal = {Ginekologia polska}, volume = {66}, number = {5}, pages = {267-271}, pmid = {8522222}, issn = {0017-0011}, mesh = {Birth Weight/*physiology ; Cephalometry ; Embryonic and Fetal Development/*physiology ; Humans ; Infant, Newborn ; Minerals/*analysis ; Placenta/*chemistry ; }, abstract = {Levels of mineral elements (F, Na, Mg, Al, S, Cl, K, Ca, V, Cr, Mn, Fe, Co, Cu, Zn, Se, Br, Rb, Mo, Cd, J, Ba, Hg and Pb), the role of which is well known and documented, were studied in 365 placentas. The significant negative correlations were ascertained between the content of Pb, Cd, F, Hg and the birth weight; the positive correlations were ascertained between some minerals (Mg, Ca, Co, Cu, Zn, Se) that are indispensable for the proper organism functioning and the fetus development.}, } @article {pmid7713994, year = {1995}, author = {Ford, I}, title = {Commentary and opinion: III. Some nonontological and functionally unconnected views on current issues in the analysis of PET datasets.}, journal = {Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism}, volume = {15}, number = {3}, pages = {371-377}, doi = {10.1038/jcbfm.1995.46}, pmid = {7713994}, issn = {0271-678X}, mesh = {Analysis of Variance ; Brain/*diagnostic imaging/*physiology ; Humans ; Longitudinal Studies ; *Statistics as Topic ; *Tomography, Emission-Computed ; }, abstract = {Strother et al. (1995) and Friston (1995) both raise important issues and provide useful reviews of various aspects of PET data analysis. Statisticians would not assume that any single piece of methodology would answer all questions about a type of data in a variety of experimental and observational contexts. The fundamental importance of hypothesis-driven inference, based on well designed experiments, cannot be overestimated for its ability to progress scientific understanding in an orderly manner. However, hypothesis-generating experiments are also vital in their own right. In practice, we generally do not have the luxury of both types of experiment, and we should note Strother et al.'s comment on the importance of extracting as much information as possible from each dataset. Friston (1995) also sees formal testing methods and exploratory methods such as principal components analysis as complementary. The correct approach would therefore seem to be (a) to select methods for formal and exploratory data analysis from the rich existing tool kit of statistical procedures, (b) to modify these as necessary to deal with special PET problems such as multiplicity, (c) to be aware of the assumptions underlying the methods being used and to investigate the problems that can arise if these assumptions fail to hold, (d) to appreciate the complexity of both PET data and of the potential questions that can be asked of it, and (e) to be aware of the limitations of any statistical analysis and the need for caution in interpreting conclusions not based on any predefined hypothesis.}, } @article {pmid7647711, year = {1995}, author = {Williams, LM}, title = {Further evidence for a multidimensional personality disposition to schizophrenia in terms of cognitive inhibition.}, journal = {The British journal of clinical psychology}, volume = {34}, number = {2}, pages = {193-213}, doi = {10.1111/j.2044-8260.1995.tb01454.x}, pmid = {7647711}, issn = {0144-6657}, mesh = {Adolescent ; Adult ; Cluster Analysis ; Cognition Disorders/*diagnosis/*etiology ; Humans ; Language Tests ; *Personality ; Photic Stimulation ; Schizophrenia/*complications ; Schizophrenic Psychology ; Semantics ; }, abstract = {A study is reported using the 'negative priming' paradigm to examine individual differences in cognitive inhibition in relation to distinct features of schizotypy. Seventy psychology students completed four measures of schizotypy, selected to index specific schizotypal traits: the Schizotypy Scale (STA), the Magical Ideation (MI) Scale, the Revised Social Anhedonia (SoA) Scale and the Physical Anhedonia (PhA) Scale. The priming paradigm was based on that of Beech, McManus, Baylis & Agar (1991), including conventional repeat and semantic priming conditions as well as repeat and semantic negative priming conditions, but differed in terms of task and stimuli. Cluster analysis of STA scores revealed a four-cluster solution reflecting 'very low', 'moderately low', 'moderately high' and 'very high' STA scores. Cluster analysis of MI, SoA, and PhA Scale scores also revealed four clusters. The first cluster comprised those with low scores on all scales. The remaining three clusters were distinguished by those with high MI, high SoA, and high PhA Scale scores, respectively. Those with high STA, MI, and SoA scale scores showed a significantly reduced, or reversed, repeat and semantic negative priming effect compared to those with moderately low STA scores and those low on all scales, respectively. An unexpected finding was that participants with high and moderately high STA scores as well as those with high MI and SoA scores revealed an inhibitory rather than facilitatory conventional repeat priming effect. It is concluded that weakening of inhibitory processes may be associated with a strong presence of schizotypal features related to dimensions of positive schizophrenic symptomatology, whereas schizotypal traits that parallel purely negative schizophrenic symptoms are not linked to reduced inhibition unless there is also a presence of 'positive' schizotypal features. The association of some schizotypal traits with an inhibitory repeat priming effect indicates that stimuli and task differences have a bearing on the attentional processes underlying priming effects for these participants. Thus, Beech et al.'s 'reduced-inhibition' model of schizophrenic symptomatology may require refinement.}, } @article {pmid7602270, year = {1995}, author = {Schacter, DL and Cooper, LA}, title = {Bias in the priming of object decisions: logic, assumption, and data.}, journal = {Journal of experimental psychology. Learning, memory, and cognition}, volume = {21}, number = {3}, pages = {768-776}, doi = {10.1037/0278-7393.21.3.768}, pmid = {7602270}, issn = {0278-7393}, support = {R01-MH45398/MH/NIMH NIH HHS/United States ; }, mesh = {*Decision Making ; Humans ; *Logic ; *Memory ; }, abstract = {R. Ratcliff and G. McKoon (1995) describe 7 experiments that led them to conclude that priming of possible but not impossible objects on the object decision task introduced by D.L. Schacter, L.A. Cooper, & S.M. Delaney (1990) is attributable to explicit memory processes that offset a bias to call studied objects "possible." On the basis of this point, Ratcliff and McKoon (1995) claim to have undermined our hypothesis that a structural description system plays an important role in object decision priming. Ratcliff and McKoon (1995) also offer a general critique of multiple memory systems accounts of priming and explicit memory. Ratcliff and McKoon's (1995) arguments are based on an inaccurate characterization of Schacter et al.'s theoretical position; the evidence for Ratcliff and McKoon's (1995) idea that explicit memory offsets bias is weak, and the central assumptions that underlie both Ratcliff and McKoon's (1995) specific experimental manipulations and their general conclusions are questionable.}, } @article {pmid7722435, year = {1995}, author = {Morrongiello, BA and Timney, B and Humphrey, GK and Anderson, S and Skory, C}, title = {Spatial knowledge in blind and sighted children.}, journal = {Journal of experimental child psychology}, volume = {59}, number = {2}, pages = {211-233}, doi = {10.1006/jecp.1995.1010}, pmid = {7722435}, issn = {0022-0965}, mesh = {Blindness/congenital/*psychology ; Child ; Child, Preschool ; Female ; Humans ; Kinesthesis ; Locomotion ; Male ; Mental Recall ; *Orientation ; Problem Solving ; *Space Perception ; Touch ; }, abstract = {Spatial knowledge was evaluated in sighted and congenitally blind children using a large-scale four-location navigation task adapted from the work of Landau, Spelke, and Gleitman (1984). From video records we coded the exact path taken and determined accuracy of initial turn, closest position, and final position, relative to target location. We then computed a score to index the efficiency of the path taken. For the sighted sample, after the navigation task, children constructed a tactile map of the test space without the aid of vision and, following removal of the blindfold, drew from memory the spatial layout of the test space. Performance on the navigation and mapping tasks consistently indicated increasing cognitive mapping skills with age in sighted children. Blind children performed comparably to the sighted on all measures except accuracy at final position, for which their performance was worse than that of the sighted. Analysis of the directness of novel paths and other measures taken suggest caution in ascribing well developed Euclidean coding skills to very young children. Results are discussed in light of Landau et al.'s (1984) conclusions.}, } @article {pmid7714481, year = {1995}, author = {Kosslyn, SM and Chabris, CF and Marsolek, CJ and Jacobs, RA and Koenig, O}, title = {On computational evidence for different types of spatial relations encoding: reply to Cook et al. (1995).}, journal = {Journal of experimental psychology. Human perception and performance}, volume = {21}, number = {2}, pages = {423-431}, doi = {10.1037//0096-1523.21.2.423}, pmid = {7714481}, issn = {0096-1523}, support = {2 PO1 17778-09//PHS HHS/United States ; }, mesh = {Brain/physiology ; Humans ; *Neural Networks, Computer ; *Space Perception ; }, abstract = {Computational models in psychology play an increasingly important role in characterizing theoretical distinctions, understanding empirical results, and formulating new predictions. However, the proper use of models is subject to debate and interpretation, as Cook, Früh, and Landis (1995) have demonstrated in a critique of neural network simulations reported by Kosslyn, Chabris, Marsolek, and Koenig (1992). These simulation results supported a distinction between two types of spatial relations encoding. Cook et al. argue that Kosslyn et al.'s models did not process "spatial" representations and that input-output correlations rather than properties of spatial relations encoding processes explain the performance of the models. This article provides conceptual and analytic rebuttals of those criticisms.}, } @article {pmid7760565, year = {1995}, author = {Evans, DM and Dunn, NJ}, title = {Alcohol expectancies, coping responses and self-efficacy judgments: a replication and extension of Copper et al.'s 1988 study in a college sample.}, journal = {Journal of studies on alcohol}, volume = {56}, number = {2}, pages = {186-193}, doi = {10.15288/jsa.1995.56.186}, pmid = {7760565}, issn = {0096-882X}, mesh = {*Adaptation, Psychological ; Adolescent ; Adult ; Alcohol Drinking ; Alcoholism/*psychology ; Female ; Humans ; Male ; *Self Concept ; Sex Factors ; Social Behavior ; Surveys and Questionnaires ; }, abstract = {OBJECTIVE: Social learning theory models of alcohol use have assumed an increasingly influential role in recent years. Despite their growing popularity, research on social learning theory models has focused almost exclusively on establishing the independent links among particular aspects of theory and indices of alcohol use and abuse. In response to the need for research that incorporates multiple aspects of theory into a testable framework, this article endeavored to replicate and extend the Copper et al. study in a college sample (Cooper, Russell and George, J. Abnorm. Psychol. Vol. 97, pp. 218-230, 1988).

METHOD: Subjects were 157 college student volunteers from a large midwestern university. Standard hierarchical multiple regression analyses were used to examine both the simultaneous and incremental contributions of self-efficacy judgments, alcohol expectancies and coping responses to dependent measures of alcohol use and alcohol-related problem behaviors.

RESULTS: Collectively, 22% of the variance in subjects' self-reported use of alcohol and greater than 50% of the variance in subjects' endorsement of alcohol-related problems was explained. Despite considerable overlap among the constructs measured, analyses also demonstrated that each variable accounted for significant and unique variance in the prediction of the criteria.

CONCLUSIONS: These results provide considerable support for the application of social learning theory principles to the drinking practices of collegiate youth. In particular, the salience of social learning theory constructs as relevant risk factors was highlighted, as lower self-efficacy judgments, positive alcohol expectancies and reliance avoidant, emotion-focused coping strategies were significantly associated with increased alcohol consumption levels and greater endorsement of alcohol-related problem behaviors.}, } @article {pmid7620637, year = {1995}, author = {Halanych, KM}, title = {The phylogenetic position of the pterobranch hemichordates based on 18S rDNA sequence data.}, journal = {Molecular phylogenetics and evolution}, volume = {4}, number = {1}, pages = {72-76}, doi = {10.1006/mpev.1995.1007}, pmid = {7620637}, issn = {1055-7903}, mesh = {Animals ; Base Sequence ; Chordata, Nonvertebrate/*classification/genetics ; DNA, Ribosomal/*genetics ; Echinodermata/classification/genetics ; Molecular Sequence Data ; *Phylogeny ; RNA, Ribosomal, 18S/*genetics ; Sequence Homology, Nucleic Acid ; Species Specificity ; }, abstract = {Pterobranchs are a class of deuterostome metazoans that are sessile marine suspension feeders. Although this group has been poorly studied, understanding their phylogenetic affinities is central to understanding early metazoan evolution. Sequence data from the 5' end of the 18S rDNA gene was collected from a pterobranch, Rhabdopleura normani, and combined with other available 18S sequences. Using standard phylogenetic methods, the evolutionary relationships of deuterostome metazoans were reconstructed. The pterobranchs are most closely related to the enteropneust hemichordates. This was confirmed by bootstrap analyses and a topology-dependent cladistic permutation tail probability (T-PTP) test. My analysis agrees with Turbeville et al.'s (1994) and Wada and Satoh's (1994) finding that hemichordates are more closely related to echinoderms than to chordates, and it is proposed that Metschnikoff's (1881) name Ambulacraria be adopted for the clade defined by the last common ancestor of the hemichordates and echinoderms. These findings suggest that ciliated gill slits and the dorsal hollow nerve chord are pleisomorphic features of the Deuterostomia.}, } @article {pmid7699723, year = {1995}, author = {Ina, Y}, title = {New methods for estimating the numbers of synonymous and nonsynonymous substitutions.}, journal = {Journal of molecular evolution}, volume = {40}, number = {2}, pages = {190-226}, pmid = {7699723}, issn = {0022-2844}, mesh = {Animals ; Computer Simulation ; Humans ; *Models, Genetic ; *Mutation ; }, abstract = {New methods for estimating the numbers of synonymous and nonsynonymous substitutions per site were developed. The methods are unweighted pathway methods based on Kimura's two-parameter model. Computer simulations were conducted to evaluate the accuracies of the new methods, Nei and Gojobori's (NG) method, Miyata and Yasunaga's (MY) method, Li, Wu, and Luo's (LWL) method, and Pamilo, Bianchi, and Li's (PBL) method. The following results were obtained: (1) The NG, MY, and LWL methods give overestimates of the number of synonymous substitutions and underestimates of the number of nonsynonymous substitutions. The major cause for the biased estimation is that these three methods underestimate the number of synonymous sites and overestimate the number of nonsynonymous sites. (2) The PBL method gives better estimates of the numbers of synonymous and nonsynonymous substitutions than those obtained by the NG, MY, and LWL methods. (3) The new methods also give better estimates of the numbers of synonymous and nonsynonymous substitutions than those obtained by the NG, MY, and LWL methods. In addition, estimates of the numbers of synonymous and nonsynonymous sites obtained by the new methods are reasonably accurate. (4) In some cases, the new methods and the PBL method give biased estimates of substitution numbers. However, from the number of nucleotide substitutions at the third position of codons, we can examine whether estimates obtained by the new methods are good or not, whereas we cannot make an examination of estimates obtained by the PBL method. (5) When there are strong transition/transversion and nucleotide-frequency biases like mitochondrial genes, all of the above methods give biased estimates of substitution numbers. In such cases, Kondo et al.'s method is recommended to be used for estimating the number of synonymous substitutions, although their method cannot estimate the number of nonsynonymous substitutions and is time-consuming. These results, particularly result (1), call for reexaminations of some genes. This is because evolutionary pictures of genes have often been discussed on the basis of results obtained by the NG, MY, and LWL methods, which are favorable for the neutral theory of molecular evolution.}, } @article {pmid7699722, year = {1995}, author = {Hein, J and Støvlbaek, J}, title = {A maximum-likelihood approach to analyzing nonoverlapping and overlapping reading frames.}, journal = {Journal of molecular evolution}, volume = {40}, number = {2}, pages = {181-189}, pmid = {7699722}, issn = {0022-2844}, mesh = {Amino Acid Sequence ; Base Sequence ; DNA, Viral/*genetics ; HIV-1/genetics ; Likelihood Functions ; *Models, Genetic ; Molecular Sequence Data ; Reading Frames/*genetics ; Sequence Alignment ; }, abstract = {A model is presented for sequence evolution on the basis of which one can analyze combinations of noncoding, singly coding, and multiply coding regions of aligned homologous DNA sequences. It is a generalization of Kimura's (J. Mol. Evol. 16:111-120, 1980) and Li et al.'s (J. Mol. Evol. 36:96-99, 1985) transition-transversion models with selection on replacement substitutions. Based on a hierarchy of hypotheses, one will be able to estimate selection factors and transition and transversion distances for different combinations of regions ranging from many regions, each with their private set of parameters, to one set of parameters for all regions. The method is demonstrated on two aligned HIV1 retroviruses.}, } @article {pmid7619133, year = {1995}, author = {Berenbaum, SA and Denburg, SD}, title = {Evaluating the empirical support for the role of testosterone in the Geschwind-Behan-Galaburda model of cerebral lateralization: commentary on Bryden, McManus, and Bulman-Fleming.}, journal = {Brain and cognition}, volume = {27}, number = {1}, pages = {79-83; discussion 94-7}, doi = {10.1006/brcg.1995.1005}, pmid = {7619133}, issn = {0278-2626}, mesh = {Adolescent ; Adult ; Animals ; Autoimmune Diseases/physiopathology ; Child ; Child, Preschool ; Dominance, Cerebral/*physiology ; Female ; Humans ; Infant ; Infant, Newborn ; Language Development Disorders/physiopathology ; Learning Disabilities/physiopathology ; *Models, Neurological ; Neural Crest/physiopathology ; Pregnancy ; *Prenatal Exposure Delayed Effects ; Testosterone/*physiology ; }, abstract = {The main tenet of the GBG model relates to the prenatal action of testosterone. Anomalies in cerebral dominance, immune functioning, abilities, and neural crest development are hypothesized to correlate with each other because all result from high levels of prenatal testosterone. Studies directly evaluating the effect of testosterone on these traits do not validate the model: sex ratios and animal studies suggest that testosterone has a protective, rather than facilitatory, effect on autoimmune diseases; individuals with high levels of early testosterone do not have elevated rates of left-handedness or learning disabilities. These findings reinforce Bryden et al.'s conclusions that there is little empirical support for the GBG model, and that it is wise to consider other theories in evaluating data derived from the model.}, } @article {pmid8547796, year = {1995}, author = {Mottur-Pilson, C}, title = {Primary care as form or content?.}, journal = {American journal of medical quality : the official journal of the American College of Medical Quality}, volume = {10}, number = {4}, pages = {177-182}, doi = {10.1177/0885713X9501000403}, pmid = {8547796}, issn = {1062-8606}, mesh = {Clinical Competence ; Humans ; Medicine/standards ; Physician-Patient Relations ; Physicians, Family/standards ; Primary Health Care/*standards ; *Quality of Health Care ; Specialization ; United States ; }, abstract = {This article advocates revisiting the notion of primary care to include these dimensions: the physician-patient relationship, the notion of principal care, and the patient as validating the primary care relationship. The quality of primary care rests squarely on these three characteristics. From a systems perspective, the quality of primary care encompasses more than the right assortment of clinical competencies; quality has to be grounded in and realized at the individual level where physician and patient meet and interact over time. The discussion thus rests on the assumption that primary care is a process of care rather than a collection of skills. This study was stimulated by two factors: the claim of subspecialists to at times provide primary care and L. H. Aiken et al.'s article on the contribution of specialists to primary care. The author of the present article surveyed 467 internists and subspecialists and asked if they equated principal care with general internal medicine (IM) care-a primary care competency. The percentage of IM in their practice was also surveyed. The 160 responses revealed that the percentage of subspecialist care to primary care was similar to that described in Aiken et al.'s article. The notion of principal care thus appears to better reflect the realities of clinical practice.}, } @article {pmid7894455, year = {1995}, author = {Sasson, A and Lewin, C and Roth, D}, title = {Dieting behavior and eating attitudes in Israeli children.}, journal = {The International journal of eating disorders}, volume = {17}, number = {1}, pages = {67-72}, doi = {10.1002/1098-108x(199501)17:1<67::aid-eat2260170109>3.0.co;2-b}, pmid = {7894455}, issn = {0276-3478}, mesh = {Child ; Cross-Cultural Comparison ; Culture ; *Diet ; *Feeding Behavior ; Female ; Humans ; Israel ; Male ; Sex Factors ; Surveys and Questionnaires ; }, abstract = {Using an Israeli school-age group, this study replicates and extends the age group of Maloney et al.'s (Pediatrics, 84, 482-489, 1989) study of American schoolchildren's abnormal eating attitudes and behaviors. Maloney's Children's Eating Attitudes Test (ChEAT) and a Demographic and Dieting Questionnaire (DDQ) were given to 186 students from Grades 3 to 6 and to 290 students from Grades 7 to 11. In Grades 3-11, 54% of students expressed a desire to lose weight and 41.6% showed behaviors aimed toward losing weight. These attitudes and behaviors were already evident in Grades 3-6. Of this group, 8.8% had ChEAT scores > or = 20 (a possible at-risk indicator of anorexia), similar to the findings of Maloney et al. Marked gender differences in the at-risk index emerged in Grades 7-11: girls, 16.3%; boys, 1.5%. Starting at Grade 8, an exacerbation was noted in girls', in contrast to boys', preoccupation with thinness and weight-losing behaviors. DDQ items were found to identify at-risk groups in Grades 5-7 and 8-11. Issues were raised concerning cross-cultural studies and strategies for timing preventative interventions.}, } @article {pmid7880952, year = {1995}, author = {Márquez Contreras, E and Gascón Vivó, J and Domínguez Gómez, B and Gutiérrez Marín, MC and Garrido Burgos, C}, title = {[Demographic classification of the family in the basic health area of La Orden, Huelva].}, journal = {Atencion primaria}, volume = {15}, number = {1}, pages = {30-32}, pmid = {7880952}, issn = {0212-6567}, mesh = {Adult ; Classification ; Confidence Intervals ; *Family Characteristics ; Female ; Humans ; Male ; Middle Aged ; Random Allocation ; Socioeconomic Factors ; Spain ; *Urban Population/statistics & numerical data ; }, abstract = {OBJECTIVE: To find the prevalence of different family structures in our health district.

DESIGN: An epidemiological study of a cross-sectional [correction of crossover] type.

SETTING: Primary Care. La Orden Health Centre in Huelva.

PARTICIPANTS: 878 individuals, who represented a family unit, selected by random sampling stratified by age and gender, obtained from the 1991 Municipal Census.

MEASUREMENTS AND MAIN RESULTS: A questionnaire was administered to all those participating in the study. This included demographic data, the number of people living in their homes, the composition of their family and the presence of close relatives in the neighbourhood. The final sample covered 787 families. Using de La Revilla et al.'s proposal, partially modified by us, the family was classified as: nuclear, extended, single-parent, without family and family equivalents. All of these were in turn sub-classified for the presence of close relatives. The nuclear family was classified as simple, numerous, amplified or binuclear. The predominant family model was nuclear (89.7%), followed by single-parent (4.4%), extended (2.9%), without family (2.4%) and family equivalents (0.6%). The main model of the nuclear family was the simple one (76.5%), followed by amplified (15.4%), leaving the numerous family in 8.1% and the binuclear at 0%. 83.5% of our families had close relatives in the same neighbourhood.

CONCLUSIONS: Our family is nuclear, with relatives nearby, a model which has definitively displaced the extended family. The structure proposed makes classification of the nuclear family easier. We believe it is essential to integrate family structure classification into Primary Care family clinical records.}, } @article {pmid7877488, year = {1995}, author = {Rzhetsky, A and Nei, M}, title = {Tests of applicability of several substitution models for DNA sequence data.}, journal = {Molecular biology and evolution}, volume = {12}, number = {1}, pages = {131-151}, doi = {10.1093/oxfordjournals.molbev.a040182}, pmid = {7877488}, issn = {0737-4038}, mesh = {*Base Sequence ; *Biological Evolution ; Computer Simulation ; DNA/chemistry/*genetics ; *Genetic Variation ; *Models, Genetic ; *Models, Statistical ; Models, Theoretical ; }, abstract = {Using linear invariants for various models of nucleotide substitution, we developed test statistics for examining the applicability of a specific model to a given dataset in phylogenetic inference. The models examined are those developed by Jukes and Cantor (1969), Kimura (1980), Tajima and Nei (1984), Hasegawa et al. (1985), Tamura (1992), Tamura and Nei (1993), and a new model called the eight-parameter model. The first six models are special cases of the last model. The test statistics developed are independent of evolutionary time and phylogeny, although the variances of the statistics contain phylogenetic information. Therefore, these statistics can be used before a phylogenetic tree is estimated. Our objective is to find the simplest model that is applicable to a given dataset, keeping in mind that a simple model usually gives an estimate of evolutionary distance (number of nucleotide substitutions per site) with a smaller variance than a complicated model when the simple model is correct. We have also developed a statistical test of the homogeneity of nucleotide frequencies of a sample of several sequences that takes into account possible phylogenetic correlations. This test is used to examine the stationarity in time of the base frequencies in the sample. For Hasegawa et al.'s and the eight-parameter models, analytical formulas for estimating evolutionary distances are presented. Application of the above tests to several sets of real data has shown that the assumption of stationarity of base composition is usually acceptable when the sequences studied are closely related but otherwise it is rejected. Similarly, the simple models of nucleotide substitution are almost always rejected when actual genes are distantly related and/or the total number of nucleotides examined is large.}, } @article {pmid7872931, year = {1995}, author = {MacLeod, C and McLaughlin, K}, title = {Implicit and explicit memory bias in anxiety: a conceptual replication.}, journal = {Behaviour research and therapy}, volume = {33}, number = {1}, pages = {1-14}, doi = {10.1016/0005-7967(94)e0004-3}, pmid = {7872931}, issn = {0005-7967}, mesh = {Adult ; Anxiety Disorders/diagnosis/*psychology ; *Arousal ; *Attention ; Female ; Humans ; Male ; *Mental Recall ; Middle Aged ; Semantics ; *Verbal Learning ; }, abstract = {Williams, Watts, MacLeod and Mathews' (1988) [Cognitive psychology and the emotional disorders. Chichester, Wiley] model of anxiety and cognition leads to the prediction that anxious subjects will show an implicit, but not an explicit, memory advantage for threat-related information. Mathews, Mogg, May and Eysenck (1989) [Journal of Abnormal Psychology, 98, 401-407] obtained marginally significant support for this prediction in an experiment that tested memory using word stem completion tasks following a self-referent encoding procedure. However, neither the reliability nor generality of these findings have been established. The current experiment was designed to provide a conceptual replication of Mathews et al.'s study, using different tests of implicit memory (i.e. tachistoscopic identification) and explicit memory (i.e. recognition) and an alternative type of encoding task (i.e. colour naming stimulus words). 16 generalised anxiety disorder patients, and 16 non-anxious control subjects were tested. As predicted, the anxiety patients showed a relative implicit memory advantage for threat-related stimulus words, while the two subject groups did not differ in their pattern of explicit memory performance. These results support the predictions generated by Williams et al.'s model of anxiety and cognition.}, } @article {pmid7742341, year = {1995}, author = {Torres, R and Fernández, F}, title = {Self-esteem and value of health as determinants of adolescent health behavior.}, journal = {The Journal of adolescent health : official publication of the Society for Adolescent Medicine}, volume = {16}, number = {1}, pages = {60-63}, doi = {10.1016/1054-139X(94)00045-G}, pmid = {7742341}, issn = {1054-139X}, mesh = {Adolescent ; Adolescent Behavior/*psychology ; Analysis of Variance ; Child ; Female ; *Health Behavior ; Humans ; Male ; *Mental Health ; *Psychology, Adolescent ; Regression Analysis ; *Self Concept ; *Social Behavior ; }, abstract = {PURPOSE: To study the relationship between personality attributes and health behaviors and practices during adolescence.

DESIGN: We have studied a total of 100 subjects aged 12-13 and 16-17 years of both sexes. To examine self-esteem and the value of health in a series of habitual practices of health, a stepwise multiple regression analysis was undertaken. The instruments used were the Gordon Personal Profile (GPP) (1978) to evaluate self-esteem, the Costa et al.'s (1989) Value of Health Scale to estimate the value of health and, the Rivas Torres (1991) Health Behavior Questionnaire to measure health behavior.

RESULTS: Self-esteem explains 39% of the mental health behavior and 5% of the social health behaviors. Meanwhile, the value of health, in the case of security behaviors, explains 13%, and in relation to personal health behaviors, 9%.

CONCLUSIONS: The importance assigned to certain personality attributes in relation to adolescent health behavior shows the need for additional investigations that incorporate other variables and subject groups with different ages.}, } @article {pmid7737071, year = {1995}, author = {Szapocznik, J}, title = {Research on disclosure of HIV status: cultural evolution finds an ally in science.}, journal = {Health psychology : official journal of the Division of Health Psychology, American Psychological Association}, volume = {14}, number = {1}, pages = {4-5}, doi = {10.1037//0278-6133.14.1.4}, pmid = {7737071}, issn = {0278-6133}, support = {1 R01 MH51402/MH/NIMH NIH HHS/United States ; }, mesh = {Acculturation ; Adult ; *Cultural Characteristics ; Family/*psychology ; HIV Infections/diagnosis/*psychology ; Hispanic or Latino/*psychology ; Humans ; Male ; *Self Disclosure ; Sexual Partners/*psychology ; Social Support ; }, abstract = {This editorial responds to Mason et al.'s (1995) "Culturally Sanctioned Secrets: Latino Men's Nondisclosure of HIV Infection to Family, Friends, and Lovers." Culture is an evolving dynamic phenomenon shaped by society, psychology, and history. Historically, familism and simpatía have been Hispanic cultural assets. As times change, however, values and behaviors that served a culture for generations may become liabilities unless they evolve to fit the changing world of the culture. In the case of Hispanic gay men, the desire to protect family members is a barrier to disclosure of HIV status. Mason et al.'s study points to areas in which cultural development is needed. Science and culture thus become allies, with science pointing the way to needed directions for adaptive cultural evolution.}, } @article {pmid7676875, year = {1995}, author = {Torres, R and Fernández, F and Maceira, D}, title = {Self-esteem and value of health as correlates of adolescent health behavior.}, journal = {Adolescence}, volume = {30}, number = {118}, pages = {403-412}, pmid = {7676875}, issn = {0001-8449}, mesh = {Adolescent ; *Adolescent Behavior ; Age Factors ; Attitude to Health ; Child ; Cross-Sectional Studies ; Female ; *Health Behavior ; Health Education ; Health Services Needs and Demand ; Humans ; Male ; *Psychology, Adolescent ; *Self Concept ; Spain ; Surveys and Questionnaires ; }, abstract = {As part of a project aimed at developing an adolescent health education program, 100 subjects aged 12-13 and 16-17 years were studied to determine the possible relationship between self-esteem and value of health and positive health behavior. Self-esteem was measured with the Gordon Personal Profile (Gordon, 1978), and value of health with Costa et al.'s (Costa, Jessor, & Donovan, 1989) Value of Health Scale. Both factors were found to be significantly correlated with certain dimensions of health behavior in both groups of adolescents.}, } @article {pmid7558681, year = {1995}, author = {Furukawa, T}, title = {Factor structure of social support and its relationship to minor psychiatric disorders among Japanese adolescents.}, journal = {The International journal of social psychiatry}, volume = {41}, number = {2}, pages = {88-102}, doi = {10.1177/002076409504100202}, pmid = {7558681}, issn = {0020-7640}, mesh = {Adolescent ; Affective Symptoms/diagnosis/ethnology/psychology ; *Cross-Cultural Comparison ; Extraversion, Psychological ; Factor Analysis, Statistical ; Female ; Humans ; Japan ; Male ; Mental Disorders/diagnosis/ethnology/*psychology ; Neurotic Disorders/diagnosis/ethnology/psychology ; Object Attachment ; Personality Assessment/statistics & numerical data ; *Personality Development ; Personality Inventory/*statistics & numerical data ; Psychometrics ; Reproducibility of Results ; Social Adjustment ; *Social Support ; }, abstract = {Although social support has been one of the preferred topics in health psychology for the past two decades, there still remains controversy about its construct and the measurement model for it. The People In Your Life (PIYL) scale, a self-report adaptation of Henderson et al.'s Interview Schedule for Social Interactions (1980), appears to be an outgrowth of the recent developments in this domain. We administered PIYL to two samples, 550 and 434 each, of Japanese adolescents and examined its factor structure, its psychometric properties and its concurrent relationship to minor psychiatric disorders. Of the original four subscales, the presence of two subscales called availability of social integration and availability of attachment was confirmed, while the remaining subscales called adequacy of social integration and adequacy of attachment were found to form one general factor of perceived adequacy. Such a three-factor model appeared to fit the data better, psychometrically more sound and externally more valid in accounting for the minor psychiatric disorders.}, } @article {pmid7481571, year = {1995}, author = {Romney, DM}, title = {Psychosocial functioning and subjective experience in schizophrenia: a reanalysis.}, journal = {Schizophrenia bulletin}, volume = {21}, number = {3}, pages = {405-410}, doi = {10.1093/schbul/21.3.405}, pmid = {7481571}, issn = {0586-7614}, mesh = {Activities of Daily Living/psychology ; Data Interpretation, Statistical ; Humans ; Interpersonal Relations ; Mathematical Computing ; Models, Statistical ; Morale ; Personal Satisfaction ; Psychiatric Status Rating Scales/*statistics & numerical data ; Psychometrics ; Schizophrenia/*diagnosis ; *Schizophrenic Psychology ; *Social Adjustment ; *Social Perception ; Socioeconomic Factors ; }, abstract = {Data collected by Brekke et al. (1993) on the symptomatology, psychosocial functioning, and subjective experience of schizophrenia outpatients were reanalyzed using LISREL to elucidate a causal model that would depict the functional relationships between the variables. The model that best fit the data parallels another model tested previously on cardiac patients and shows that subjective experience is much more influenced by symptomatology than by social functioning. This confirms Brekke et al.'s main finding. The implications of these results for intervention and for future research are considered.}, } @article {pmid7844481, year = {1994}, author = {Hurford, DP and Johnston, M and Nepote, P and Hampton, S and Moore, S and Neal, J and Mueller, A and McGeorge, K and Huff, L and Awad, A}, title = {Early identification and remediation of phonological-processing deficits in first-grade children at risk for reading disabilities.}, journal = {Journal of learning disabilities}, volume = {27}, number = {10}, pages = {647-659}, doi = {10.1177/002221949402701005}, pmid = {7844481}, issn = {0022-2194}, mesh = {Child ; Dyslexia/*prevention & control/psychology ; Educational Status ; Female ; Follow-Up Studies ; Humans ; Male ; *Phonetics ; *Remedial Teaching ; Risk Factors ; }, abstract = {The present study assessed 486 first-quarter first graders on their reading and phonological-processing skills and intelligence. Based on this assessment, and using the classification data from Hurford et al.'s (1993) study, 99 children were identified as being at risk for reading difficulties: 53 children at risk for reading disabilities (RD) and 46 children at risk for becoming "garden-variety" poor readers (GV). Half of the RD and GV groups received the phonological-processing intervention. Posttraining assessment indicated that the training procedure not only was effective in increasing the phonological-processing skills of the trained participants, but also increased their reading ability. Both of the RD and GV trained groups benefited from the training. Analyses also indicated that the initial screening device was somewhat less accurate in the present study in identifying at-risk children than in our previous studies (85% vs. approximately 98%, respectively). The results of the present study indicate that it is possible to identify children at risk for reading difficulties and to significantly improve their phonological-processing and reading abilities.}, } @article {pmid7963022, year = {1994}, author = {Lively, SE and Pisoni, DB and Yamada, RA and Tohkura, Y and Yamada, T}, title = {Training Japanese listeners to identify English /r/ and /l/. III. Long-term retention of new phonetic categories.}, journal = {The Journal of the Acoustical Society of America}, volume = {96}, number = {4}, pages = {2076-2087}, pmid = {7963022}, issn = {0001-4966}, support = {R01 DC000111/DC/NIDCD NIH HHS/United States ; K08 DC000111/DC/NIDCD NIH HHS/United States ; NIDCD DC-00012-14/DC/NIDCD NIH HHS/United States ; F32 DC000111/DC/NIDCD NIH HHS/United States ; T32 DC000012/DC/NIDCD NIH HHS/United States ; NIDCD DC-00111-16/DC/NIDCD NIH HHS/United States ; }, mesh = {Female ; Humans ; Japan ; *Language ; Male ; *Phonetics ; *Speech ; *Speech Production Measurement ; Verbal Learning ; }, abstract = {Monolingual speakers of Japanese were trained to identify English /r/ and /l/ using Logan et al.'s [J. Acoust. Soc. Am. 89, 874-886 (1991)] high-variability training procedure. Subjects' performance improved from the pretest to the post-test and during the 3 weeks of training. Performance during training varied as a function of talker and phonetic environment. Generalization accuracy to new words depended on the voice of the talker producing the /r/-/l/ contrast: Subjects were significantly more accurate when new words were produced by a familiar talker than when new words were produced by an unfamiliar talker. This difference could not be attributed to differences in intelligibility of the stimuli. Three and six months after the conclusion of training, subjects returned to the laboratory and were given the post-test and tests of generalization again. Performance was surprisingly good on each test after 3 months without any further training: Accuracy decreased only 2% from the post-test given at the end of training to the post-test given 3 months later. Similarly, no significant decrease in accuracy was observed for the tests of generalization. After 6 months without training, subjects' accuracy was still 4.5% above pretest levels. Performance on the tests of generalization did not decrease and significant differences were still observed between talkers. The present results suggest that the high-variability training paradigm encourages a long-term modification of listeners' phonetic perception. Changes in perception are brought about by shifts in selective attention to the acoustic cues that signal phonetic contrasts. These modifications in attention appear to be retrained over time, despite the fact that listeners are not exposed to the /r/-/l/ contrast in their native language environment.}, } @article {pmid8083684, year = {1994}, author = {Zucker, KJ and Blanchard, R}, title = {Reanalysis of Bieber et al.'s 1962 data on sibling sex ratio and birth order in male homosexuals.}, journal = {The Journal of nervous and mental disease}, volume = {182}, number = {9}, pages = {528-530}, doi = {10.1097/00005053-199409000-00009}, pmid = {8083684}, issn = {0022-3018}, mesh = {*Birth Order ; Family ; Female ; Homosexuality/psychology/*statistics & numerical data ; Humans ; Male ; Sex Distribution ; *Sex Ratio ; }, } @article {pmid7932793, year = {1994}, author = {Zharkikh, A}, title = {Estimation of evolutionary distances between nucleotide sequences.}, journal = {Journal of molecular evolution}, volume = {39}, number = {3}, pages = {315-329}, pmid = {7932793}, issn = {0022-2844}, mesh = {Base Sequence/*genetics ; *Biological Evolution ; Markov Chains ; Models, Genetic ; Models, Theoretical ; Point Mutation/genetics ; Probability ; Stochastic Processes ; }, abstract = {A formal mathematical analysis of the substitution process in nucleotide sequence evolution was done in terms of the Markov process. By using matrix algebra theory, the theoretical foundation of Barry and Hartigan's (Stat. Sci. 2:191-210, 1987) and Lanave et al.'s (J. Mol. Evol. 20:86-93, 1984) methods was provided. Extensive computer simulation was used to compare the accuracy and effectiveness of various methods for estimating the evolutionary distance between two nucleotide sequences. It was shown that the multiparameter methods of Lanave et al.'s (J. Mol. Evol. 20:86-93, 1984), Gojobori et al.'s (J. Mol. Evol. 18:414-422, 1982), and Barry and Hartigan's (Stat. Sci. 2:191-210, 1987) are preferable to others for the purpose of phylogenetic analysis when the sequences are long. However, when sequences are short and the evolutionary distance is large, Tajima and Nei's (Mol. Biol. Evol. 1:269-285, 1984) method is superior to others.}, } @article {pmid7931102, year = {1994}, author = {Nicol, JL and Fodor, JD and Swinney, D}, title = {Using cross-modal lexical decision tasks to investigate sentence processing.}, journal = {Journal of experimental psychology. Learning, memory, and cognition}, volume = {20}, number = {5}, pages = {1229-1238}, doi = {10.1037/0278-7393.20.5.1229}, pmid = {7931102}, issn = {0278-7393}, support = {DC-01409/DC/NIDCD NIH HHS/United States ; }, mesh = {*Cognition ; *Decision Making ; Humans ; *Language ; }, abstract = {Recent investigations of sentence processing have used the cross-modal lexical decision task to show that the antecedent of a phonologically empty noun phrase (specifically, WH-trace) is reactivated at the trace position. G. McKoon, R. Ratcliff, and G. Ward (1994) claimed that (a) a design feature concerning the choice of related and unrelated targets is a possible confound in this work and (b) the conclusions drawn from this previous research are therefore called into question. These claims are considered in light of both McKoon et al.'s experimental findings and results of our own experiments in which we test their linguistic materials. We argue that their results may be due to the nature of their materials. Additionally, we argue that a follow-up experiment reported by G. McKoon and R. Ratcliff (1994) used a technique that is not comparable to the cross-modal lexical decision task. It is concluded that current evidence supports the claim that structural information is using during on-line sentence processing and that the cross-modal technique is sensitive to this.}, } @article {pmid7969869, year = {1994}, author = {Pasquier, F and Van der Linden, M and Lefebvre, V and Lefebvre, C and Bruyer, R and Petit, H}, title = {Motor memory and the preselection effect in Huntington's and Parkinson's disease.}, journal = {Neuropsychologia}, volume = {32}, number = {8}, pages = {951-968}, doi = {10.1016/0028-3932(94)90045-0}, pmid = {7969869}, issn = {0028-3932}, mesh = {Adult ; Aged ; Female ; Humans ; Huntington Disease/*complications ; Male ; Memory Disorders/*etiology ; Middle Aged ; *Movement ; Parkinson Disease/*complications ; Severity of Illness Index ; }, abstract = {Patients with Huntington's disease (HD) and Parkinson's disease (PD) show different patterns of preserved and impaired memory performance. This study investigates explicit memory for movements in HD and PD with a linear positioning apparatus using Dick et al.'s procedure (J. Gerontol. 43, 127-135, 1988). In the first experiment, 12 HD patients were compared to 12 matched-controls. HD patients were more impaired than the controls by the delay between criterion and recall movements, whether the delay was filled or unfilled. Switching the limb between criterion and recall movements did not lead to more effects in HD patients and in controls. In the second experiment, 12 non-demented PD patients were compared to matched-controls. PD patients were more impaired than controls when the recall movement was executed with the contralateral hand, but were not more affected by the delay. In both experiments, HD and PD patients, as well as the controls, recalled self-generated preselected movements better than imposed movements. These results suggest the existence of distinct forms of motor memory impairment in some subcortical neurodegenerative diseases.}, } @article {pmid8078399, year = {1994}, author = {Cao, Y and Adachi, J and Yano, T and Hasegawa, M}, title = {Phylogenetic place of guinea pigs: no support of the rodent-polyphyly hypothesis from maximum-likelihood analyses of multiple protein sequences.}, journal = {Molecular biology and evolution}, volume = {11}, number = {4}, pages = {593-604}, doi = {10.1093/oxfordjournals.molbev.a040139}, pmid = {8078399}, issn = {0737-4038}, mesh = {Animals ; Crystallins/chemistry ; Cytochrome b Group/chemistry ; Electron Transport Complex IV/chemistry ; Guinea Pigs/*classification/genetics ; Hemoglobins/chemistry ; Likelihood Functions ; Molecular Sequence Data ; Myoglobin/chemistry ; *Phylogeny ; Primates/classification/genetics ; Rodentia/classification/genetics ; Vertebrates/classification/genetics ; }, abstract = {Graur et al.'s (1991) hypothesis that the guinea pig-like rodents have an evolutionary origin within mammals that is separate from that of other rodents (the rodent-polyphyly hypothesis) was reexamined by the maximum-likelihood method for protein phylogeny, as well as by the maximum-parsimony and neighbor-joining methods. The overall evidence does not support Graur et al.'s hypothesis, which radically contradicts the traditional view of rodent monophyly. This work demonstrates that we must be careful in choosing a proper method for phylogenetic inference and that an argument based on a small data set (with respect to the length of the sequence and especially the number of species) may be unstable.}, } @article {pmid7946250, year = {1994}, author = {Reiss, S}, title = {Issues in defining mental retardation.}, journal = {American journal of mental retardation : AJMR}, volume = {99}, number = {1}, pages = {1-7}, pmid = {7946250}, issn = {0895-8017}, mesh = {Attitude ; Consumer Behavior ; Cultural Characteristics ; Humans ; Intellectual Disability/classification/*diagnosis/psychology ; Intelligence ; Public Policy ; United States ; }, abstract = {Responses were made to MacMillan, Gresham, and Siperstein's (1993) criticisms of the new AAMR definition. The new AAMR definition does not raise the IQ limit and is not intended to increase the number of people considered to have mental retardation. There is no intent to change who is and who is not considered to have mental retardation. Instead, the intent is to change how people think about mental retardation: The old deficiency model is replaced with a new support model. MacMillan et al.'s criticisms are based on unfortunate misstatements of both the 1983 and the 1992 AAMR definitions of mental retardation and on misunderstandings of psychometric science. On the one hand, they argued that intelligence tests are culturally biased. On the other hand, they criticized the AAMR for not making greater use of inflexible IQ cutoffs in defining mental retardation. They misunderstood that cultural bias is an argument for, not against, flexibility in the interpretation of intelligence tests.}, } @article {pmid8084724, year = {1994}, author = {Sohmiya, T and Sohmiya, K}, title = {What is a crucial determinant in anorthoscopic perception?.}, journal = {Perceptual and motor skills}, volume = {78}, number = {3 Pt 1}, pages = {987-998}, doi = {10.1177/003151259407800357}, pmid = {8084724}, issn = {0031-5125}, mesh = {*Attention ; Discrimination Learning ; Female ; Humans ; Male ; *Motion Perception ; *Optical Illusions ; Orientation ; *Pattern Recognition, Visual ; *Perceptual Closure ; Psychophysics ; }, abstract = {There are two important problems in anorthoscopic perception. The first is how a sequence of parts of a figure viewed through a slit is integrated into a whole. The second is how the distortion of an anorthoscopic image along the direction of its motion occurs. To answer the questions, two experiments and two demonstrations were performed by conceiving compound figures of one horizontal and one curvilinear component and a method which permits seeing anorthoscopic and ordinary images at the same time. From the results, the idea of anorthoscopic motion complementary to apparent motion is introduced as a crucial determinant that permits an integration of the parts into a perception of the whole. As regards the distortion of the percept we agree with Rock, et al.'s 1987 assumption but also consider that the distortion depends on the ratio of speed of anorthoscopic motion to real motion.}, } @article {pmid8080704, year = {1994}, author = {Zimmerman, RS and Olson, K}, title = {AIDS-related risk behavior and behavior change in a sexually active, heterosexual sample: a test of three models of prevention.}, journal = {AIDS education and prevention : official publication of the International Society for AIDS Education}, volume = {6}, number = {3}, pages = {189-204}, pmid = {8080704}, issn = {0899-9546}, mesh = {Acquired Immunodeficiency Syndrome/prevention & control/*psychology ; Adult ; *Attitude to Health ; Female ; Health Behavior ; Health Knowledge, Attitudes, Practice ; *Health Promotion ; Humans ; Male ; Models, Psychological ; Predictive Value of Tests ; Regression Analysis ; *Risk-Taking ; *Sexual Behavior ; Sexual Partners ; Surveys and Questionnaires ; }, abstract = {Because a cure and a vaccine for the human immunodeficiency virus (HIV) are not expected for at least several years, prevention of AIDS is the only means of reducing the spread of the disease. While education, information, and persuasion may be changing the HIV-related attitudes and even behaviors of some individuals, without a theoretical framework, the reasons why some individuals have changed and why other individuals have not changed are elusive. Three social-psychological models that have been applied to health-related behavior--the Health Belief Model (HBM), the Ajzen-Fishbein attitude-behavior model (AFM), and Leventhal et al.'s Self-Regulatory Model (SRM)--are tested in this study. The extent to which each model's variables are related to self-reported behavior change related to HIV and current HIV-related behavior are compared. Results indicate that the SRM and AFM contributed significantly to predicting risk behavior change, and that the HBM and AFM contributed significantly to predicting current risk behavior, after controlling for risk behavior change. Significant predictors of risk behavior change included timeline, identity, and self-efficacy from the SRM; sexual impulse (a barrier) from the HBM; and attitudes about the behaviors from the AFM. Significant predictors of current risk behavior included several barriers from the HBM and negative attitude about risk-reducing behaviors from the AFM.}, } @article {pmid7896385, year = {1994}, author = {Rao, DH and Rao, KM and Radhaiah, G and Rao, NP}, title = {Nutritional status of tribal preschool children in three ecological zones of Madhya Pradesh.}, journal = {Indian pediatrics}, volume = {31}, number = {6}, pages = {635-640}, pmid = {7896385}, issn = {0019-6061}, mesh = {Anthropometry ; Child ; Child Nutrition Disorders/*ethnology/etiology/physiopathology ; Child, Preschool ; *Energy Intake ; Female ; *Food ; Growth Disorders/*ethnology/etiology/physiopathology ; Humans ; India/epidemiology ; Infant ; Male ; *Native Hawaiian or Pacific Islander ; *Nutritional Status ; Racial Groups ; }, abstract = {A health and nutrition survey was conducted on tribals in three ecological zones of Madhya Pradesh namely Jhabua (West Zone), Bastar (South Zone) and Sarguja (East Zone) taking into consideration the relative contribution of agriculture, forest and a combination of both to the economy, respectively. The consumption of both foods and nutrients appear to be worse among preschool children of Jhabua compared to Bastar and Sarguja. Clinically overt forms of Protein Energy Malnutrition and other vitamin deficiency signs were strikingly low. However, 4% of children in Sarguja exhibited signs of goitre. Both by extent and severity of malnutrition, the children of Jhabua appear to be worse followed by Bastar and Sarguja.}, } @article {pmid8200092, year = {1994}, author = {Melchior, WB and Marques, MM and Beland, FA}, title = {Mutations induced by aromatic amine DNA adducts in pBR322.}, journal = {Carcinogenesis}, volume = {15}, number = {5}, pages = {889-899}, doi = {10.1093/carcin/15.5.889}, pmid = {8200092}, issn = {0143-3334}, mesh = {2-Acetylaminofluorene/toxicity ; Amines/*toxicity ; Amino Acid Sequence ; Aminobiphenyl Compounds/toxicity ; Benzidines/toxicity ; DNA/*drug effects/*genetics/metabolism ; Deoxyguanosine/metabolism ; Escherichia coli/genetics ; Fluorenes/toxicity ; Hydrocarbons/*toxicity ; Molecular Sequence Data ; *Mutation ; Plasmids/*drug effects/*genetics ; Pyrenes/toxicity ; Tetracycline Resistance/genetics ; Transfection ; }, abstract = {A 276 bp region from the tetracycline resistance gene of the plasmid pBR322 was modified with 2-acetylaminofluorene (AAF), 2-aminofluorene (AF), 4-aminobiphenyl (ABP), N'-acetylbenzidine or 1-aminopyrene (AP) in order to determine the effect of adduct structure upon mutation induction. Each modification reaction gave one major adduct and these adducts had chromatographic properties, as determined by 32P-postlabeling, identical to those in which substitution had occurred at C8 of deoxyguanosine through the amine or amide nitrogen. The types and distribution of mutations were then characterized following introduction of the modified plasmids into SOS-induced Escherichia coli using Hanahan et al.'s procedure (Methods Enzymol., 204, 63-113, 1991). With AAF-modified plasmid, 60% of the mutations were deletions or additions, and these were detected primarily at NarI sites or in repetitive G sequences. Modification with AF gave -G deletions, primarily in runs of Gs, and base substitution mutations, which were mainly G to T transversions. Substitution with ABP or N'-acetylbenzidine resulted in G to T and G to C transversions, the latter being a mutation not detected with AF; in addition, -G deletions were detected at only very low frequency. AP modification gave both -G frameshift and base substitution mutations, of which G to T transversions predominated. A comparison of the mutation frequencies per adduct indicated that the mutagenic efficiencies of the adducts decreased in the order AP > AF > AAF approximately ABP approximately N'-acetylbenzidine. AAF- and ABP-modified pBR322 were also introduced with a CaCl2 method. The mutation frequency per adduct increased with this transformation procedure, and this appeared to be a reflection of a greater percentage of frameshift mutations. These data indicate that a series of structurally related aromatic amines will induce both base substitution and frameshift mutations when incorporated into pBR322, but that frameshift mutations occur almost exclusively with the planar derivatives. Furthermore, the ability to induce frameshift mutations increases the mutagenic efficiency of an adduct.}, } @article {pmid8002417, year = {1994}, author = {Mansour, AA and Hassan, SA}, title = {Factors that influence women's nutrition knowledge in Saudi Arabia.}, journal = {Health care for women international}, volume = {15}, number = {3}, pages = {213-223}, doi = {10.1080/07399339409516113}, pmid = {8002417}, issn = {0739-9332}, mesh = {Adult ; Chi-Square Distribution ; Educational Status ; Female ; Humans ; Lactation ; Nutritional Requirements ; *Nutritional Sciences/*education ; Pregnancy ; Saudi Arabia ; Women/*education ; }, abstract = {We studied knowledge of nutritional needs during pregnancy and lactation in 150 pregnant Saudi women at three primary health care centers in Riyadh, Saudi Arabia. We used an interview schedule to collect data regarding the women's knowledge and to determine the effects of certain independent variables on the knowledge scores. Green et al.'s (1980) PRECEDE model provided the theoretical framework for the study. Descriptive statistics, t test, and chi-square methods were used to analyze the data. The majority of the women had poor nutrition knowledge scores, with no significant differences among the three centers. A positive relationship was found between knowledge score and educational level. Negative relationships were found between knowledge score and number of pregnancies, number of deliveries, and number of living children. The findings have several implications for efforts to improve the health status of women in Saudi Arabia.}, } @article {pmid8189198, year = {1994}, author = {Shapiro, KL and Raymond, JE and Arnell, KM}, title = {Attention to visual pattern information produces the attentional blink in rapid serial visual presentation.}, journal = {Journal of experimental psychology. Human perception and performance}, volume = {20}, number = {2}, pages = {357-371}, doi = {10.1037//0096-1523.20.2.357}, pmid = {8189198}, issn = {0096-1523}, mesh = {Adult ; *Attention ; *Discrimination Learning ; Female ; Humans ; Male ; Orientation ; *Pattern Recognition, Visual ; Psychophysics ; Reaction Time ; *Serial Learning ; }, abstract = {To-investigate the temporal allocation of attention, a series of 7 experiments using rapid serial visual presentation (RSVP) was designed to examine the relationship of the attentional demands of various target tasks to the production of the subsequent visual attentional deficit, or "attentional blink" (AB), recently reported by J. E. Raymond, K. L. Shapiro, and K. M. Arnell (1992). The principal finding is that AB occurs only when a target is an object and does not occur when the target is defined by a temporal interval. Target detection difficulty as estimated by d' analysis reveals no relationship between the attentional demands of the target and the production of the AB. A late-selection account of this phenomenon is offered in place of the early-selection account advanced in Raymond et al.'s previous report.}, } @article {pmid8138780, year = {1994}, author = {Broerse, J and Grimbeek, P}, title = {Eye movements and the associative basis of contingent color aftereffects: a comment on Siegel, Allan, and Eissenberg (1992).}, journal = {Journal of experimental psychology. General}, volume = {123}, number = {1}, pages = {81-85}, doi = {10.1037//0096-3445.123.1.81}, pmid = {8138780}, issn = {0096-3445}, mesh = {Adolescent ; Adult ; *Association Learning ; *Color Perception ; *Eye Movements ; Fixation, Ocular ; Form Perception ; Humans ; *Optical Illusions ; Photic Stimulation ; }, abstract = {One of S. Siegel, L. G. Allen, and T. Eissenberg's (1992) recent arguments in support of associative-learning explanations of colored aftereffects (CAEs) is that the contingencies underlying these effects are not constrained by simple stimulus dimensions, such as contour orientation. Specifically, the authors claim to have generated CAEs contingent on sets of spatiotopic relationships between orientation components of a pattern (as opposed to orientation components per se). The present article illustrates how Siegel et al.'s claims are compromised by their failure to adequately address the role of fixation and eye movements during CAE induction.}, } @article {pmid8153242, year = {1994}, author = {Hong, SM and Giannakopoulos, E}, title = {Effects of age, sex, and university status on life-satisfaction.}, journal = {Psychological reports}, volume = {74}, number = {1}, pages = {99-103}, doi = {10.2466/pr0.1994.74.1.99}, pmid = {8153242}, issn = {0033-2941}, mesh = {Adolescent ; Adult ; Age Factors ; *Educational Status ; Female ; Humans ; Male ; *Personal Satisfaction ; Personality Inventory ; *Quality of Life ; Sex Factors ; }, abstract = {Diener, et al.'s 1985 Satisfaction With Life Scale was administered to 1749 adult Australians to examine differences between men and women, university students and nonuniversity students, and among 17- to 22-, 23- to 29-, and 30- to 40-yr.-olds. No significant differences in life-satisfaction emerged in relation to sex or university status, but age showed a significant effect as higher life-satisfaction characterized older subjects. No interactions were found for any combination of the three variables. The results are interpreted in terms of egalitarian sex-role ideologies regarding sex, status-specific criteria in the assessment and conceptualisation of life-satisfaction for university status, and maturity trends in viewing life events concerning age.}, } @article {pmid8090995, year = {1994}, author = {Coelho, A and Momen, H and Vicente, AC and Salles, CA}, title = {An analysis of the V1 and V2 regions of Vibrio cholerae and Vibrio mimicus 16S rRNA.}, journal = {Research in microbiology}, volume = {145}, number = {2}, pages = {151-156}, doi = {10.1016/0923-2508(94)90008-6}, pmid = {8090995}, issn = {0923-2508}, mesh = {Cloning, Molecular ; *Genes, Bacterial ; In Vitro Techniques ; Polymerase Chain Reaction/*methods ; RNA, Ribosomal, 16S/*analysis ; Sequence Analysis, RNA ; Vibrio/*genetics ; Vibrio cholerae/*genetics ; }, abstract = {The V1 and V2 variable regions of the 16S rRNA gene of three strains of V. cholerae and one strain of V. mimicus were amplified by PCR. Fragments containing both regions were cloned into M13mp18 using Smal and sequenced by the dideoxy method. The 263-bp sequence from a strain isolated during the 1991 cholera outbreak in Brazil was deposited in Genbank under the accession number L05178. Except for an extra G in one of the strains, the three V. cholerae sequences were identical. The V. mimicus sequence was very similar, with only two substitutions. We compared these sequences with the Vibrio 16S rRNA sequences described by Dorsch et al. in 1992. It was noted that the V1 region, including helix 6 and its associated loop, comprised two different sizes and sequences in the various Vibrio species. While V. cholerae, V. mimicus, V. vulnificus, V. anguillarum and V. diazotrophicus had a 46-nucleotide V1, other species such as V. parahaemolyticus, V. proteolyticus, V. alginolyticus, V. campbellii and V. hollisae had longer 54- or 55-nucleotide regions, with a different consensus sequence. The phylogeny of Vibrio was analysed using the sequenced region and its equivalent in other species, by means of the "Phylip" software package. Species with a short helix 6 were grouped together, as were species with a long helix. Dorsh et al.'s analysis is discussed in relation to this "helix 6 split".}, } @article {pmid8276680, year = {1994}, author = {Thomas, C and Koh, WJ}, title = {Regarding Keane et al.'s randomized trial comparing radiation alone to concomitant infusional 5-flurorouracil, bolus mitomycin-C and split-course radiation.}, journal = {International journal of radiation oncology, biology, physics}, volume = {28}, number = {2}, pages = {557}, doi = {10.1016/0360-3016(94)90091-4}, pmid = {8276680}, issn = {0360-3016}, mesh = {Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Fluorouracil/administration & dosage ; Humans ; Hypopharyngeal Neoplasms/drug therapy/*radiotherapy ; Laryngeal Neoplasms/drug therapy/*radiotherapy ; Mitomycin/administration & dosage ; Randomized Controlled Trials as Topic ; }, } @article {pmid8188492, year = {1994}, author = {Norris, AE and Ford, K}, title = {Condom beliefs in urban, low income, African American and Hispanic youth.}, journal = {Health education quarterly}, volume = {21}, number = {1}, pages = {39-53}, doi = {10.1177/109019819402100106}, pmid = {8188492}, issn = {0195-8402}, support = {1 RO1 HD26250/HD/NICHD NIH HHS/United States ; }, mesh = {Acculturation ; Acquired Immunodeficiency Syndrome/*prevention & control/psychology/transmission ; Adolescent ; Adult ; Black or African American/*psychology ; *Condoms ; Cross-Cultural Comparison ; Female ; *Health Knowledge, Attitudes, Practice ; Hispanic or Latino/*psychology ; Humans ; Male ; Midwestern United States ; Poverty/*psychology ; *Urban Population ; }, abstract = {This article focuses on the condom beliefs of low income, urban African American and Hispanic youth living in the Midwest. The condom beliefs under investigation were derived from prior research with members of this population and through consultation with African American and Hispanic youth and service providers. Significant gender, ethnic, and acculturation differences were found among beliefs related to frequency of condom use in the past year (p < .05). These differences indicated that women, African American respondents, and Hispanic respondents high in acculturation tended to have more neutral or more positive views about condoms than other types of respondents.}, } @article {pmid8165836, year = {1994}, author = {Wurl, C and Dudenhausen, JW}, title = {[Ultrasonographic determination of amniotic fluid--comparison of two methods].}, journal = {Zeitschrift fur Geburtshilfe und Perinatologie}, volume = {198}, number = {1}, pages = {22-26}, pmid = {8165836}, issn = {0300-967X}, mesh = {Adult ; Amniotic Fluid/*physiology ; Female ; Gestational Age ; Humans ; Infant, Newborn ; Pregnancy ; Reference Values ; Ultrasonography, Prenatal/*methods ; }, abstract = {A study was performed in order to find a suitable ultrasonographic method of determining amniotic fluid volumes. Volumes were measured in 398 gravidae with no fetal or maternal pathology. The Depot V method described by Chamberlain et al. and Phelan et al.'s four-quadrant method were used to perform the measurements. Normal-value curves were prepared from the results. The reproducibility of the two methods was also verified. The results of the study showed that the normal-value curve derived from the four-quadrant method was in very good agreement with the results of the quantitative indicator dilution methods described by Queenan et al., which also indicated a marked decrease in volume after GW 34. It may be concluded from this that the four-quadrant method produces representative figures for the actual volume of amniotic fluid. A further distinctive feature of the four-quadrant methods is its very good reproducibility. The decrease in the fluid volume towards the end of gestation could not be demonstrated by the Depot V method. The four-quadrant method may therefore be regarded as a suitable semi-quantitative ultrasonographic method of determining the amniotic fluid volume.}, } @article {pmid8156052, year = {1994}, author = {Ferreirós, CM and Ferrón, L and Criado, MT}, title = {In vivo human immune response to transferrin-binding protein 2 and other iron-regulated proteins of Neisseria meningitidis.}, journal = {FEMS immunology and medical microbiology}, volume = {8}, number = {1}, pages = {63-68}, doi = {10.1111/j.1574-695X.1994.tb00426.x}, pmid = {8156052}, issn = {0928-8244}, mesh = {Animals ; Antibodies, Bacterial/*immunology ; Bacterial Outer Membrane Proteins/*immunology ; Carrier Proteins/*immunology ; Cerebrospinal Fluid/microbiology ; Cross Reactions ; Humans ; Iron/metabolism ; Iron-Binding Proteins ; Meningitis, Meningococcal/blood/cerebrospinal fluid/immunology/microbiology ; Mice ; Neisseria meningitidis/classification/*immunology/isolation & purification ; Serotyping ; Transferrin-Binding Protein B ; Transferrin-Binding Proteins ; }, abstract = {When grown under iron restriction, Neisseria meningitidis expresses new outer-membrane proteins, some of which are antigenic and potentially useful as vaccine components. This is particularly relevant to N. meningitidis serogroup B, against which neither polysaccharide nor conjugate vaccines are effective. We investigated recognition of N. meningitidis serogroup B outer-membrane antigens by three sera from patients recovered from meningitis. Recognition of antigens from the homologous strain provided information on in vivo expression during infection and immunogenicity, while cross-reactivity with outer membrane proteins from the other two strains and from another five strains in our collection allowed evaluation of antigenic heterogeneity. Our results demonstrate that transferrin-binding protein 2 (TBP2) is immunogenic in humans, to varying degrees depending on the strain, and that TBP2s (like the equivalent proteins of Haemophilus influenzae type b) are among the most important iron-regulated outer membrane antigens expressed during infection. Other immunogenic outer membrane proteins (some iron-regulated) are also expressed during infection; in a previous study in mouse, three of these proteins (with M(r) of 50, 70 and 77 kDa) did not induce an immune response. Our cross-reactivity data provide some support for Robki et al.'s two-group classification of N. meningitidis strains, and provide evidence against the possibility that the antigenic domains shared by the TBP2s of all N. meningitidis strains induce immune responses in vivo.}, } @article {pmid7987693, year = {1994}, author = {Darlu, P and Sagnier, PP and Bois, E}, title = {[Evidences for genetic transmission of pulse arterial pressure].}, journal = {Comptes rendus de l'Academie des sciences. Serie III, Sciences de la vie}, volume = {317}, number = {1}, pages = {62-69}, pmid = {7987693}, issn = {0764-4469}, mesh = {Blood Pressure/*genetics ; Data Interpretation, Statistical ; Diastole ; Female ; Humans ; Male ; Pulse/*genetics ; Systole ; West Indies ; }, abstract = {Systolic (PS), diastolic (PD), and pulse (PULS) arterial blood pressure were examined in 151 French-West-Indies families. After adjustment for sex, age, Na/K urinary ratio, alcohol consumption, use of anti-hypertensive drug, the distributions of PS and PD were correctly fitted by two commingled normal distributions, one of them including 5% of the highest values of blood pressure which have to be compared to the high prevalence of hypertension in this population (10 to 20%). By performing segregation analyses under Lalouel et al.'s unified model we do not support any genetic transmission for PS and PD. On the contrary, large evidence for genetic transmission of PULS was found, involving one locus, two equally frequent alleles. However dominance cannot be correctly inferred. Accordingly, PULS appears to be of larger interest than PS and PD to study the genetic regulation of the arterial blood pressure.}, } @article {pmid7971943, year = {1994}, author = {Robichaud-Ekstrand, S and Sherrard, H}, title = {Cardiac nurses' perceptions of nursing research.}, journal = {Progress in cardiovascular nursing}, volume = {9}, number = {3}, pages = {7-15}, pmid = {7971943}, issn = {0889-7204}, mesh = {Adult ; Analysis of Variance ; *Attitude of Health Personnel ; *Cardiology/statistics & numerical data ; *Clinical Nursing Research/statistics & numerical data ; Humans ; Middle Aged ; Nursing Staff, Hospital/*psychology/statistics & numerical data ; Ontario ; Reproducibility of Results ; *Specialties, Nursing/statistics & numerical data ; Surveys and Questionnaires ; }, abstract = {Nurses' perception of nursing research is an important variable affecting the successful development of a clinical nursing research program. The objectives of this study were to: examine the perceived value, role, interest, support and experience of cardiac nurses in nursing research; to determine the effects of age and level of education on their perceptions; and to analyze the reliability of Alcock et al.'s questionnaire. The survey was administered to 313 nurses with a response rate of 46%. Frequency distributions were obtained on individual survey items. MANOVAs were performed as a function of age group and education level, followed by post hoc ANOVAs. Findings showed nurses valued nursing research particularly as it related to clinical practice decisions and solutions to patient care problems. They saw a participatory role in the first stages of the research process. Age was not a factor in nurses' perceptions of nursing research with the exception of perceived support. Diploma nurses indicated higher levels of perceived value (p = 0.000), role (p = 0.034), interest (p = 0.000) and support (p = 0.017) for nursing research than baccalaureate nurses. The Cronbach reliability coefficient of each area indicated high internal consistency (> 0.72). When 5 items in the questionnaire are deleted, the tool exhibits high level of reliability and evidence of construct and discriminant validity.}, } @article {pmid7889450, year = {1994}, author = {Robichaud-Ekstrand, S and Haccoun, RR and Millette, D}, title = {[A method for validating a translated questionnaire].}, journal = {The Canadian journal of nursing research = Revue canadienne de recherche en sciences infirmieres}, volume = {26}, number = {3}, pages = {77-87}, pmid = {7889450}, issn = {0844-5621}, mesh = {Nursing Research/instrumentation ; Reproducibility of Results ; Surveys and Questionnaires/*standards ; *Translating ; }, abstract = {This paper describes Haccoun's (1987) technique for validating a translated questionnaire. This method is based on the idea that if a questionnaire is well translated, bilingual subjects will provide equivalent responses to questions in either language. A single group of bilingual subjects is given both language versions of the questionnaires at two different times in random order. Subsequently: 1) test-retest reliability coefficients are computed for the original and translated versions; 2) correlation coefficients between the original and translated versions of the instrument are computed and compared (simultaneous correlations between languages); 3) the correlations between the original version at time 1 and the translated version at time 2 and vice versa are computed and compared (cross-correlations); and 4) the cross-correlations are compared to the test-retest reliabilities within each language. The final step indicates whether the translated version of the instrument is equivalent to the original. The authors use Haccoun's technique to demonstrate that a French translated version of Alcock et al.'s (1990) questionnaire on nurses' perceptions of nursing research is reliable and statistically equivalent to the original.}, } @article {pmid7701283, year = {1994}, author = {Grove, WM and Iacono, WG}, title = {Comment on Levy et al. "Eye tracking dysfunction and schizophrenia".}, journal = {Schizophrenia bulletin}, volume = {20}, number = {4}, pages = {781-786}, doi = {10.1093/schbul/20.4.781}, pmid = {7701283}, issn = {0586-7614}, mesh = {*Attention/physiology ; Biomarkers ; Depressive Disorder/diagnosis/genetics/physiopathology/psychology ; Genetic Markers/genetics ; Humans ; Models, Genetic ; *Pursuit, Smooth/genetics/physiology ; Schizophrenia/*diagnosis/genetics/physiopathology ; *Schizophrenic Psychology ; }, abstract = {We agree with Levy et al.'s conclusion (Schizophrenia Bulletin, Vol. 19, No. 3, 1993) that global quantitative measures of eye tracking dysfunction (ETD) have an important role in studies of ETD in schizophrenia. We clarify some misunderstandings of our own work contained in their review. In particular, an explanation is presented of how we computed a fit of our data to their Mendelian latent structure model, when testing for a fit to their hypothesis of essential genetic homogeneity. We also point out that our mixture analyses, as with our reported abnormality rates obtained by using cutting scores, are not in agreement with their reported rates of ETD in schizophrenia.}, } @article {pmid8294522, year = {1993}, author = {Ehlers, S and Gillberg, C}, title = {The epidemiology of Asperger syndrome. A total population study.}, journal = {Journal of child psychology and psychiatry, and allied disciplines}, volume = {34}, number = {8}, pages = {1327-1350}, doi = {10.1111/j.1469-7610.1993.tb02094.x}, pmid = {8294522}, issn = {0021-9630}, mesh = {Adolescent ; Autistic Disorder/diagnosis/*epidemiology/psychology ; Child ; Child Development Disorders, Pervasive/diagnosis/*epidemiology/psychology ; Cross-Sectional Studies ; Diagnosis, Differential ; Female ; Humans ; Incidence ; Intellectual Disability/diagnosis/epidemiology/psychology ; Male ; Mass Screening ; Neurocognitive Disorders/diagnosis/epidemiology/psychology ; Personality Assessment/statistics & numerical data ; Psychometrics ; Sweden/epidemiology ; }, abstract = {This paper describes a total population study of Asperger syndrome using a two-stage procedure. All school children in an outer Göteborg borough were screened. Final case selection based on clinical work-up showed a minimum prevalence of 3.6 per 1.000 children (7-16 years of age) using Gillberg and Gillberg's criteria and a male to female ratio of 4:1. Including suspected and possible Asperger syndrome cases, the prevalence rose to 7.1 per 1.000 children and the male:female ratio dropped to 2.3:1. These findings are discussed as they relate to previously published results in the field and to findings obtained using Szatmari et al.'s and ICD-10 draft criteria for the disorder.}, } @article {pmid8289662, year = {1993}, author = {Burns, DJ and Curti, ET and Lavin, JC}, title = {The effects of generation on item and order retention in immediate and delayed recall.}, journal = {Memory & cognition}, volume = {21}, number = {6}, pages = {846-852}, pmid = {8289662}, issn = {0090-502X}, mesh = {Adolescent ; Adult ; Female ; Humans ; Language ; Language Tests ; Male ; *Memory ; *Mental Recall ; *Retention, Psychology ; Vocabulary ; }, abstract = {Recent research has shown that generating words from fragments, relative to simply reading them, inhibits processing of order information. Nairne, Riegler, and Serra (1991) showed that this reduction in processing of order information leads to deficits in recall performance. In three experiments, we generally replicate Nairne et al.'s results and demonstrate that the deficit in recall for the generated items is dependent on the easy distractor task and the relatively short (30-sec) retention interval they used. When a difficult distractor task was used, generating produced a deficit in amount of order information processed, but actually facilitated recall when recall was delayed 80 sec. The results are consistent with the hypothesis that generating words inhibits order processing, but they do not support the contention that the reduction in order processing is responsible for the deficit in recall that is sometimes observed for the generated items. The importance of the item-order distinction in explaining the generation effect, as well as the role of the item-order distinction in the long-term-memory arena, is questioned.}, } @article {pmid8271801, year = {1993}, author = {Howard, MO}, title = {Assessing the comparative cost-effectiveness of alcoholism treatments: a comment on Holder, Longabaugh, Miller and Rubonis.}, journal = {Journal of studies on alcohol}, volume = {54}, number = {6}, pages = {667-675}, doi = {10.15288/jsa.1993.54.667}, pmid = {8271801}, issn = {0096-882X}, mesh = {Alcoholism/economics/*rehabilitation ; Aversive Therapy/*economics ; Cost-Benefit Analysis ; Humans ; Treatment Outcome ; }, abstract = {Holder, Longabaugh, Miller and Rubonis (JSA, vol. 53, pp. 517-540, 1991) discuss the shortcomings of the empirical literature relevant to an assessment of the comparative cost-effectiveness of alcoholism treatment modalities. Their analysis is rooted in an attempt to conjoin the literatures pertaining to clinical efficacy and costs of alcohol dependence treatment. Holder et al.'s methodology is flawed in a number of respects and they exceed the bounds of the evidence when they endorse particular treatment modalities as comparatively cost-effective. Generalizations as to the relative cost-effectiveness of particular modalities are forwarded despite the fact that treatments are applied to persons with alcohol problems of widely varying severity. Additional points of contention are raised regarding the authors' selection of acceptable studies and interpretation of findings. Despite these limitations, Holder et al.'s (1991) analysis is a seminal heuristic contribution to the discussion of cost-effectiveness in the alcoholism field.}, } @article {pmid8270730, year = {1993}, author = {Ghitza, O}, title = {Processing of spoken CVCs in the auditory periphery. I. Psychophysics.}, journal = {The Journal of the Acoustical Society of America}, volume = {94}, number = {5}, pages = {2507-2516}, doi = {10.1121/1.407386}, pmid = {8270730}, issn = {0001-4966}, mesh = {Female ; Humans ; Male ; Phonetics ; *Psychophysics ; Sound Spectrography ; Speech Acoustics ; *Speech Intelligibility ; *Speech Perception ; Time Factors ; Vestibulocochlear Nerve ; }, abstract = {This study provides a quantitative measure of the accuracy of the auditory periphery in representing prespecified time-frequency regions of initial and final diphones of spoken CVCs. The database comprised word pairs that span the speech space along Jakobson et al.'s binary phonemic features [Tech. Rep. No. 13, Acoustic Laboratory, MIT, Cambridge, MA (1952)]. The time-frequency domain was divided into "tiles" by splitting the frequency range into three bands ([0,1000], [1000,2500], [2500,4000]Hz), and by marking the phonemic time landmarks of the CVC utterance. Fourteen modified versions of this database were generated by introducing well-defined distortions into the time-frequency tiles (or combination of tiles). The performance of eight listeners was measured for each of these versions by using a one-interval two-alternative forced-choice paradigm, to minimize the role of cognition. The results demonstrate that in the first and the second frequency bands, the diphone information is far more important than the consonant information or the vowel information alone. As for the third band, most of the information of the diphone is contained in the consonantal time interval. These observations are common to both the initial and the final consonants of spoken CVCs. The study also provides a direct mapping between Jakobson et al.'s features and particular regions in the time-frequency domain. Voicing and nasality are strongly correlated with the diphone information in the first frequency band, graveness and compactness with the diphone information in the second frequency band, and sibilation with the consonantal time interval in the third frequency band.(ABSTRACT TRUNCATED AT 250 WORDS)}, } @article {pmid8247655, year = {1993}, author = {Fudin, R}, title = {Final comments on Hudesman, Page, and Rautiainen's (1992) subliminal psychodynamic activation experiment.}, journal = {Perceptual and motor skills}, volume = {77}, number = {2}, pages = {367-370}, doi = {10.2466/pms.1993.77.2.367}, pmid = {8247655}, issn = {0031-5125}, mesh = {*Educational Status ; Humans ; Mathematics ; *Object Attachment ; *Problem Solving ; *Psychoanalytic Theory ; *Subliminal Stimulation ; }, abstract = {Hudesman, et al.'s (1992) contention that their finding shows that subliminal psychodynamic activation (SPA) improved academic performance is questioned. That experiment lacked controls outlined by Fudin in 1986 which are needed to support the assumption that a positive SPA outcome is effected because the meaning of an entire experimental message is encoded. In 1993 Hudesman and Page argued that Gustafson and Källmén's 1991 results, obtained with such controls, indicated that the controls do not have to be used in subsequent SPA experiments. The 1990 results of Greenberg and of Kothera, Fudin, and Nicastro, however, do not support those of Gustafson and Källmén. From a different perspective, it is argued that good experimental controls are needed in all SPA experiments because they increase internal validity. Given that Hudesman, et al.'s subjects scored in a limited range on the mathematics portion of the 1978 CUNY Skills Assessment Test, the implication that their result can be generalized to all subjects is questioned.}, } @article {pmid8408964, year = {1993}, author = {Lively, SE and Logan, JS and Pisoni, DB}, title = {Training Japanese listeners to identify English /r/ and /l/. II: The role of phonetic environment and talker variability in learning new perceptual categories.}, journal = {The Journal of the Acoustical Society of America}, volume = {94}, number = {3 Pt 1}, pages = {1242-1255}, pmid = {8408964}, issn = {0001-4966}, support = {R01 DC000111/DC/NIDCD NIH HHS/United States ; K08 DC000111/DC/NIDCD NIH HHS/United States ; F32 DC000111/DC/NIDCD NIH HHS/United States ; T32 DC000012/DC/NIDCD NIH HHS/United States ; DC-00111-15/DC/NIDCD NIH HHS/United States ; NIDCD DC0012-14/DC/NIDCD NIH HHS/United States ; }, mesh = {Acoustic Stimulation ; *Environment ; Female ; Humans ; Japan/ethnology ; *Learning ; Male ; *Phonetics ; Speech Acoustics ; *Speech Perception ; Speech Production Measurement ; United States ; }, abstract = {Two experiments were carried out to extend Logan et al.'s recent study [J. S. Logan, S. E. Lively, and D. B. Pisoni, J. Acoust. Soc. Am. 89, 874-886 (1991)] on training Japanese listeners to identify English /r/ and /l/. Subjects in experiment 1 were trained in an identification task with multiple talkers who produced English words containing the /r/-/l/ contrast in initial singleton, initial consonant clusters, and intervocalic positions. Moderate, but significant, increases in accuracy and decreases in response latency were observed between pretest and posttest and during training sessions. Subjects also generalized to new words produced by a familiar talker and novel words produced by an unfamiliar talker. In experiment 2, a new group of subjects was trained with tokens from a single talker who produced words containing the /r/-/l/ contrast in five phonetic environments. Although subjects improved during training and showed increases in pretest-posttest performance, they failed to generalize to tokens produced by a new talker. The results of the present experiments suggest that variability plays an important role in perceptual learning and robust category formation. During training, listeners develop talker-specific, context-dependent representations for new phonetic categories by selectively shifting attention toward the contrastive dimensions of the non-native phonetic categories. Phonotactic constraints in the native language, similarity of the new contrast to distinctions in the native language, and the distinctiveness of contrastive cues all appear to mediate category acquisition.}, } @article {pmid8406197, year = {1993}, author = {Kennedy, AW and Biscotti, CV and Hart, WR and Tuason, LJ}, title = {Histologic correlates of progression-free interval and survival in ovarian clear cell adenocarcinoma.}, journal = {Gynecologic oncology}, volume = {50}, number = {3}, pages = {334-338}, doi = {10.1006/gyno.1993.1221}, pmid = {8406197}, issn = {0090-8258}, mesh = {Adenocarcinoma, Clear Cell/mortality/*pathology/surgery ; Female ; Humans ; Mitotic Index ; Neoplasm Staging ; Ovarian Neoplasms/mortality/*pathology/surgery ; Prognosis ; Proportional Hazards Models ; Retrospective Studies ; Risk Factors ; }, abstract = {Unlike other ovarian epithelial cancers, histologic measures of differentiation of ovarian clear cell adenocarcinoma have not been found to be reliable predictors of progression-free interval and survival. Forty-two consecutively treated patients with pure ovarian clear cell adenocarcinoma were identified and all histologic materials were reviewed. The following histologic features were assessed: architectural pattern (tubular/tubulocystic, papillary, solid, and mixed), average and maximal mitotic activity per 10 high-power fields (hpf's), percentage of cells with clear cytoplasm, and nuclear grading (both Fuhrman et al.'s (Am. J. Surg. Pathol. 6, 655-663, 1982) and Christopherson et al.'s (Cancer 49, 1511-1523, 1982) methods). Surgical stage was most predictive of survival (P < 0.01) and subsequent comparisons using Cox proportional hazards modeling were adjusted for Stages III and IV. Greater than six mitotic figures per 10 hpf's predicted a poorer survival (P = 0.05) but was not predictive of progression-free interval (P = 0.28). Survival and progression-free interval in patients with tumors of mixed architectural pattern tended to be shorter than those for patients where one type did predominate, but this was not statistically significant (P = 0.06). The tubulocystic pattern was not predictive of patient outcome nor was either method of nuclear grading. Stage and average mitotic activity seem to be the best predictors of survival for patients with ovarian clear cell adnocarcinoma, while architectural pattern and nuclear grading are not as reliable.}, } @article {pmid8144064, year = {1993}, author = {Ottaviano, S and Innocenzi, M and Ottaviano, P and Antignani, M and Bruni, O and Giannotti, F}, title = {Short temperament questionnaire for children aged 8-12 years in the city of Rome.}, journal = {Functional neurology}, volume = {8}, number = {5}, pages = {365-371}, pmid = {8144064}, issn = {0393-5264}, mesh = {Child ; Female ; Humans ; Italy ; Male ; *Personality Assessment/statistics & numerical data ; Psychometrics ; Reproducibility of Results ; *Surveys and Questionnaires ; *Temperament ; }, abstract = {The assessment of temperament is usually measured by means of parental questionnaires. Since temperament questionnaires in children aged 8-12 years do not exist in Italy we planned a study to develop an Italian questionnaire. Initially we tried to adapt Hegvik et al.'s questionnaire and delivered 389 questionnaires to the mothers of children aged 8-12 years, but most of them were given back uncompleted, essentially because they often described behavior not usually observed in Italian children. Then we prepared a new, short (30 items) questionnaire which we distributed to 431 mothers of children aged 8-12 years. This new questionnaire was completed by 98.76% of mothers and a high three week rating-re-rating reliability for the different temperamental characteristics under assessment was proved. We believe that this new questionnaire is reliable for temperament assessment in Italian children aged 8 to 12 years, living in a big city environment in Central Italy.}, } @article {pmid8353713, year = {1993}, author = {Brown, RG and Jahanshahi, M and Marsden, CD}, title = {Response choice in Parkinson's disease. The effects of uncertainty and stimulus-response compatibility.}, journal = {Brain : a journal of neurology}, volume = {116 (Pt 4)}, number = {}, pages = {869-885}, doi = {10.1093/brain/116.4.869}, pmid = {8353713}, issn = {0006-8950}, support = {//Wellcome Trust/United Kingdom ; }, mesh = {Aged ; *Choice Behavior ; Female ; Humans ; Male ; Middle Aged ; Parkinson Disease/*physiopathology ; *Reaction Time ; }, abstract = {Reaction time paradigms provide a set of methods for assessing aspects of the planning and execution of voluntary movements in Parkinson's disease. Attention has focused mainly on the issue of programming of responses, employing a combination of simple reaction time (SRT) and choice reaction time (CRT) paradigms. The first part of the present study replicated an earlier finding in which patients showed a disproportionate slowing in CRT compared with SRT. The main aim of the study was to investigate the possible role of response choice, a key stage prior to motor programming in this CRT deficit. Two factors were manipulated: (i) response uncertainty and (ii) stimulus-response compatibility. The patients showed a normal increase in reaction time with increasing uncertainty in the compatible conditions, and a normal response to stimulus-response compatibility in the two-choice task. However, the two groups showed qualitatively different patterns of interaction between the two experimental factors, with only the patients showing a disproportionate slowing with incompatible stimulus-response relationships in the four-choice task. The data were interpreted in terms of Hasbroucq et al.'s (1990) list-rule model of stimulus-response compatibility effects, which suggested that the patients and controls were using different strategies for dealing with incompatible stimulus-response relationships. The use of different strategies makes it impossible to determine whether or not the processing of the patients is impaired in Parkinson's disease, although further research is suggested to clarify the question. However, the present data suggest that any impairment in response choice is unlikely to contribute to the slowing in CRT in Parkinson's disease under conditions of high stimulus-response compatibility.}, } @article {pmid8261772, year = {1993}, author = {Wijnand, HP}, title = {Bioequivalence revisited: non-parametric analysis of two-period cross-over studies.}, journal = {Computer methods and programs in biomedicine}, volume = {40}, number = {4}, pages = {249-259}, doi = {10.1016/0169-2607(93)90010-i}, pmid = {8261772}, issn = {0169-2607}, mesh = {Algorithms ; Analysis of Variance ; Angina Pectoris/drug therapy ; Bepridil/administration & dosage ; *Computer Simulation ; *Confidence Intervals ; Delayed-Action Preparations ; Double-Blind Method ; Humans ; Isosorbide Dinitrate/pharmacokinetics ; Male ; Mathematical Computing ; Reference Values ; Software ; Theophylline/pharmacokinetics ; *Therapeutic Equivalency ; Verapamil/administration & dosage ; }, abstract = {Hauschke et al.'s non-parametric bioequivalence procedure for treatment effects and some aspects of computer implementation, among them Meineke and De Hey's algorithm and a recursive algorithm, are explored. For studies with up to sixty subjects, a table of indices of the ranked intersubject-intergroup mean ratios or differences is given, to establish non-parametric 90% confidence intervals. It is shown that non-parametric analysis is not limited to treatment effects: it can also be applied to period and sequence effects. This extended procedure can be seen as the non-parametric analogue of analysis of variance on two-period cross-over studies. A FORTRAN program (BIOEQNEW) incorporating Meineke and De Mey's algorithm is presented. This program provides non-parametric point estimates for treatment and period effects, 90% and 95% confidence intervals for test-versus-reference treatments, the 95% confidence interval for periods and a test on sequence effects, so that it can also be used for other than bioequivalence studies. BIOEQNEW can handle ratios ('multiplicative model') as well as differences ('additive model'). It optionally provides the complete non-parametric posterior probability distribution for treatment ratios or differences, so that Schuirmann's 'two one-sided tests procedure' can also be performed in a non-parametric way.}, } @article {pmid8210667, year = {1993}, author = {Kunzendorff, E and Scholl, U and Scholl, M}, title = {[Quality of life and coping in the comparison of various groups of chronic illness during inpatient rehabilitation].}, journal = {Die Rehabilitation}, volume = {32}, number = {3}, pages = {177-184}, pmid = {8210667}, issn = {0034-3536}, mesh = {*Adaptation, Psychological ; Chronic Disease ; Defense Mechanisms ; Female ; Humans ; Liver Diseases/*psychology/rehabilitation ; Male ; Middle Aged ; Myocardial Infarction/*psychology/rehabilitation ; Neuropsychological Tests ; Physician-Patient Relations ; *Quality of Life ; Self-Assessment ; Social Support ; Stress, Psychological ; }, abstract = {The concept of adaptation and quality of life has gained central importance in the research on chronically ill patients and their rehabilitation. This contribution examines the impact of psychological and behavioural factors on the quality of life and coping processes in two groups of chronically ill patients (i.e., n = 48 myocardial infarction survivors, and n = 48 patients with liver diseases). Coping responses and quality of life were measured using Janke et al.'s stress coping questionnaire SVF (1985), while other variables (psychosocial stress and social support) were determined by a variety of self-report data, test measures (von Zerssen's emotional state scale, 1976), as well as interview data, with repeat data compilation after three years (longitudinal study). Significant differences were found for each of the patient groups. Effectiveness of coping appeared to be negatively linked with frequent use of "avoidance", "denial", and "resignation" in patients with psychosocial strain and lack of information. The choice of coping strategy seems to be multi-determined and is related to illness state and sex, with changes occurring over time. The knowledge of coping strategy preferences is highly relevant for the relationship between physician and patient as well as for the process of rehabilitation.}, } @article {pmid8412882, year = {1993}, author = {Bareman, FP and Nijenhuis, EM and Dokter, HJ and Trijsburg, W and Out, J and Braams, FM}, title = {Dissatisfied patients: improving general practitioners' initial reactions.}, journal = {Medical education}, volume = {27}, number = {4}, pages = {382-388}, doi = {10.1111/j.1365-2923.1993.tb00286.x}, pmid = {8412882}, issn = {0308-0110}, mesh = {Attitude of Health Personnel ; Clinical Competence ; Communication ; Family Practice/*education ; *Patient Satisfaction ; Physician-Patient Relations ; }, abstract = {General practitioners often have difficulty in dealing with dissatisfied patients. One underlying reason could be the disturbed relationship between the doctor and the dissatisfied patient. A training course has been developed taking the relationship as a starting-point. Based on Watzlawick et al.'s theory on communication GPs have been trained to react to a dissatisfied patient on a relational level ('Are you dissatisfied with my treatment?') rather than on a contents level ('How long have you been suffering from this?'). This method seeks to improve the relationship and the satisfaction of both doctor and patient. Three types of initial reaction to dissatisfied patients were offered to four groups of GPs (19 trainees in general practice and 19 trainers in general practice). Pre- and post-measurement were executed by means of registering the initial reactions on videorecorded vignettes of re-enacted dissatisfied patients. Subsequently the reactions were categorized blind by two judges. The 12 possible categories can be subdivided into categories primarily aimed at the contents or primarily aimed at the relationship. The results show that, as compared to the pre-measurements, GPs more frequently use empathic reactions and reactions in which they bring their own actions up for discussion. The number of responses in which doctors ask a further clinical question or in which GPs expect a solution whether from themselves or from others, decrease. It is concluded that the course appears to change for the better the GPs' initial reaction to dissatisfied patients.}, } @article {pmid8404799, year = {1993}, author = {Cacioppo, JT and Gardner, WL}, title = {What underlies medical donor attitudes and behavior?.}, journal = {Health psychology : official journal of the Division of Health Psychology, American Psychological Association}, volume = {12}, number = {4}, pages = {269-271}, doi = {10.1037//0278-6133.12.4.269}, pmid = {8404799}, issn = {0278-6133}, mesh = {Attitude to Health ; Blood Donors/*psychology ; Female ; *Helping Behavior ; Humans ; Male ; Motivation ; Registries ; *Tissue Banks/statistics & numerical data ; *Tissue Donors/statistics & numerical data ; }, abstract = {Donor attitudes, intentions, and behaviors have typically been conceptualized as organized along a bipolar continuum. This conceptualization is evident in I. G. Sarason et al.'s study of increasing participation in a bone-marrow registry in this issue. When the cumulative research on blood, bone-marrow, and organ donor behavior is considered, however, evidence suggests that a single, bipolar continuum may be insufficient and that a 2-dimensional (Positivity x Negativity) evaluative space may be minimally required to effectively represent and target the underlying substrates of donor behaviors. Negative beliefs and fears may constitute a particularly difficult obstacle to inducing donor behaviors and, thus, to promoting self-perceptions by people as donors. Understanding and changing these negative substrates, therefore, may be important if public health campaigns to increase donor behavior are to be cost-effective.}, } @article {pmid8346875, year = {1993}, author = {Ogden, TL and Bartlett, IW and Purnell, CJ and Wells, CJ and Armitage, F and Wolfson, H}, title = {Dust from cotton manufacture: changing from static to personal sampling.}, journal = {The Annals of occupational hygiene}, volume = {37}, number = {3}, pages = {271-285}, doi = {10.1093/annhyg/37.3.271}, pmid = {8346875}, issn = {0003-4878}, mesh = {Dust/*analysis ; Environmental Monitoring/*instrumentation/methods ; *Gossypium ; Humans ; Occupational Exposure/*analysis ; Reference Values ; *Textile Industry ; }, abstract = {Several designs of personal samplers were tested for use to collect cotton dust. The IOM personal inhalable-dust sampler was selected because: (1) collection of the whole inhalable fraction was preferred, since all inhaled sizes are under suspicion as contributing to respiratory symptoms in cotton exposure; (2) this sampler is well characterized; and (3) it was found to be practicable in the environments examined. Gauze shields to exclude 'fly' from the personal sampler were tried, but were rejected mainly because measurement of the whole inhalable fraction by a validated sampler was felt to be more appropriate. A range of processes at a representative selection of mills was assessed by a hygiene team, and classified as 'clean' or 'dirty' in terms of present standards of control. This classification agreed well with subsequent measurements using the present method, which uses a large static sampler. A personal sampling survey then showed that in about two-thirds of 'clean' processes personal exposure of at least 80% of those employed was less than about 2-2.5 mg m-3. Only one-tenth of 'dirty' processes met this standard. Personal exposure correlates poorly with the present static method, as expected, but comparison of the results suggested that a mean background level of 0.5 mg m-3 would correspond to a median personal exposure of about 2.2 mg m-3. Side-by-side measurements by the background method differed by less than 0.15 mg m-3 on about 95% of occasions. Niven et al. (to be published) have compared the IOM head used in this study with the Manchester University sampler previously used by Cinkotai et al. [Ann. occup. Hyg. 32, 103-113 (1988)] to derive a relationship between personal exposure and prevalence of byssinotic symptoms in spinners. According to Cinkotai et al.'s results the concentrations of 2-2.5 mg m-3 discussed would correspond to a prevalence of 3-5%. However, this prevalence probably reflects higher exposures in the past.}, } @article {pmid8332694, year = {1993}, author = {Dua, J and Plumer, G}, title = {Relationship between attributional style, individualized attributional style, and health.}, journal = {Psychological reports}, volume = {72}, number = {3 Pt 1}, pages = {913-914}, doi = {10.2466/pr0.1993.72.3.913}, pmid = {8332694}, issn = {0033-2941}, mesh = {Depression/*psychology ; *Helplessness, Learned ; Humans ; *Internal-External Control ; Life Change Events ; Personality Inventory ; *Sick Role ; Students, Nursing/psychology ; }, abstract = {Attributional styles as measured by Peterson, et al.'s 1982 questionnaire and through an individualized questionnaire were not differentially related to measures of physical and psychological health for 27 nursing students.}, } @article {pmid8332689, year = {1993}, author = {Rutledge, PC and Hollenberg, D and Hancock, RA}, title = {Individual differences in the Wegner rebound effect: evidence for a moderator variable in thought rebound following thought suppression.}, journal = {Psychological reports}, volume = {72}, number = {3 Pt 1}, pages = {867-880}, doi = {10.2466/pr0.1993.72.3.867}, pmid = {8332689}, issn = {0033-2941}, support = {GM-08202/GM/NIGMS NIH HHS/United States ; }, mesh = {Aptitude ; *Attention ; Educational Status ; Humans ; Mathematics ; *Mental Recall ; Obsessive Behavior/*psychology ; *Thinking ; }, abstract = {Wegner, Schneider, Carter, and White in 1987 found that attempts to suppress thoughts of a white bear produced even greater preoccupation with that stimulus--a rebound effect. This effect was investigated in Exp. 1 using both Wegner's white bear stimulus and a more personally meaningful stimulus (an upcoming test). The rebound effect was not observed with either stimulus. Exp. 2 was conducted to examine the hypothesis that this failure to replicate Wegner, et al.'s rebound effect reflected individual differences in the respective subject pools. A within-subjects design was used to classify subjects as rebounders or nonrebounders by comparing each subject's expression of a thought following suppression to their own baseline expression of that thought. Subjects classified as rebounders had significantly higher ACT Mathematics subtest scores than did the subjects classified as nonrebounders. This suggests that there is a moderator variable related to mathematics ability for the rebound effect.}, } @article {pmid8321599, year = {1993}, author = {Fudin, R}, title = {Comments on Hudesman and Page's reply to Fudin's comments on Hudesman, Page and Rautianen's subliminal psychodynamic activation experiment.}, journal = {Perceptual and motor skills}, volume = {76}, number = {3 Pt 1}, pages = {856-858}, doi = {10.2466/pms.1993.76.3.856}, pmid = {8321599}, issn = {0031-5125}, mesh = {*Arousal ; *Attention ; Generalization, Psychological ; Humans ; Object Attachment ; *Problem Solving ; *Psychoanalytic Theory ; *Subliminal Stimulation ; }, abstract = {Hudesman and Page's contention that Gustafson and Källmén's 1991 results indicate that subsequent subliminal psychodynamic activation experiments do not require the controls suggested by Fudin in 1986 is questioned. The rationale for Fudin's 1993 comment concerning the limited generalizability of Hudesman, et al.'s (1992) results, a comment Hudesman and Page contended is unfounded, is discussed.}, } @article {pmid8311031, year = {1993}, author = {Malgady, RG and Rogler, LH}, title = {Mental health status among Puerto Ricans, Mexican Americans, and non-Hispanic whites: the case of the misbegotten hypothesis.}, journal = {American journal of community psychology}, volume = {21}, number = {3}, pages = {383-8; discussion 389-95}, doi = {10.1007/BF00941508}, pmid = {8311031}, issn = {0091-0562}, mesh = {*Cross-Cultural Comparison ; Cross-Sectional Studies ; Hispanic or Latino/psychology/*statistics & numerical data ; Humans ; Incidence ; Mental Disorders/*epidemiology/psychology ; Mexican Americans/psychology/*statistics & numerical data ; Social Values ; United States/epidemiology ; White People/psychology/*statistics & numerical data ; }, abstract = {Challenged Shrout et al.'s (1992) comparisons of mental health characteristics of island Puerto Ricans to Mexican Americans and non-Hispanic whites from the Los Angeles Epidemiological Catchment Area Study. The hypothesis tested by Shrout et al.--higher symptom counts but lower DSM-III prevalence rates among Puerto Ricans--was misattributed to Rogler (1989). We also question the validity of assessing lifetime prevalence and reaffirm the need for psychiatric epidemiological research to consider the role of culture in diagnostic criteria.}, } @article {pmid8500641, year = {1993}, author = {Geronimus, AT and Korenman, S}, title = {The socioeconomic costs of teenage childbearing: evidence and interpretation.}, journal = {Demography}, volume = {30}, number = {2}, pages = {281-90; discussion 291-6}, pmid = {8500641}, issn = {0070-3370}, mesh = {Adolescent ; Adult ; Cohort Studies ; Female ; Humans ; Infant, Newborn ; Longitudinal Studies ; Pregnancy ; *Pregnancy in Adolescence ; Sampling Studies ; *Socioeconomic Factors ; }, abstract = {There is little evidence to support the reasons suggested by Hoffman et al. for treating the results based on the NLSYW as outliers. There is even some evidence that might lead one to favor the NLSYW estimates. After some investigation, which of the range of within-family estimates across data sets is most accurate remains unsettled (although exploring differences in cross-sectional estimates from the sisters subsamples seems promising). In addition, we believe there is evidence to support the hypothesis that within-family estimates are upwardly biased because of within-family heterogeneity and endogeneity, but the importance and magnitude of such bias is also an open question. Although we have highlighted here what we believe to be the main points of disagreement between ourselves and Hoffman et al., we hope readers will not lose sight of the areas of agreement between the two studies, which are substantial, or of the empirical support for our key findings that Hoffman et al.'s replication study has provided. To us, the findings of both studies suggest that future research should account empirically for potential biases from (possibly unmeasured) heterogeneity in family background. Because the prevailing beliefs about the consequences of teen childbearing have been based on cross-sectional comparisons that lack detailed family background controls, these beliefs now should be open for reconsideration and should be subjected to reevaluation. Several recent empirical attempts have been made to take heterogeneity or endogeneity bias into account. These studies support this conclusion and caution against drawing causal inferences from existing estimates of the effects of teen births. We continue to recognize the limitations of currently available methods and data for accounting for unobserved heterogeneity and selectivity (e.g., Griliches 1979; Manski 1989). Therefore we encourage the enhancement of data sets and the continued empirical investigation of questions that have been raised about possible biases of sibling estimation and other methodological approaches. We hope that with new rounds of research, advances will continue to further the understanding of these important social processes. Given the difficulty of accounting adequately for selection into teen childbearing across and within populations, and even within families, and given the conflicting within-family estimates, we believe that the size of any "true effects" of teen births on socioeconomic status must be considered an open question.}, } @article {pmid8491052, year = {1993}, author = {Libbey, NP and Chazan, JA and London, MR and Pono, L and Abuelo, JG}, title = {The relevance of mineralization lag time in the evaluation of histologic changes in renal osteodystrophy.}, journal = {Clinical nephrology}, volume = {39}, number = {4}, pages = {214-223}, pmid = {8491052}, issn = {0301-0430}, mesh = {Bone Density/physiology ; Bone Remodeling/physiology ; Bone and Bones/*pathology ; Calcification, Physiologic/*physiology ; Chronic Kidney Disease-Mineral and Bone Disorder/classification/*pathology/physiopathology ; Female ; Humans ; Kidney Failure, Chronic/pathology/therapy ; Male ; Renal Dialysis ; }, abstract = {We examined bone biopsies from 47 patients on chronic hemodialysis, and analyzed the histomorphometric and biochemical findings and histologic quantitation of bone aluminium, looking primarily at mineralization lag time (Mlt) to evaluate its usefulness in categorization of renal osteodystrophy (ROD). The patients were categorized as having either relatively normal Mlt (< 35 days, n = 21 patients), moderately prolonged Mlt (35-100 days, n = 13 patients) or markedly prolonged Mlt (> 100 days, n = 13 patients). The group with relatively normal Mlt showed significantly higher C-terminal parathyroid hormone (PTHc) levels (26,141 +/- 19,270 vs 7,226 +/- 6,073 and 4,434 +/- 4,000 pg/ml) than the moderately or markedly prolonged Mlt groups (p < .01) and was associated with histologic characteristics of osteitis fibrosa or mild hyperparathyroidism (BFR/BS range 0.146-0.947 mcm3/mcm2/d). The group with markedly prolonged Mlt included one patient with classic and 11 with adynamic osteomalacia (BFR/BS range 0.009-0.099) and had greater bone aluminum (Al.S/OS 35.3 +/- 26.7% vs 7.2 +/- 9.0%) than the normal Mlt group (p < .01). The group with moderately prolonged Mlt included two patients with aplastic bone disease (Mlt 80.0 and 84.6 days, and Al.S/OS 100.0 and 72.3%) and 11 patients with features of hyperparathyroidism and osteomalacia (BFR/BS range 0.068-0.243) with variable but generally intermediate bone aluminum deposition (Al.S/OS 22.5 +/- 19.9%). Like BFR/BS and other dynamic parameters Mlt correlates with morphologic types of ROD which primarily reflect bone turnover, but it may also suggest varying degrees of mineralization impairment in a spectrum ranging from high to low turnover types of ROD. Its usefulness in this respect should not be overlooked.}, } @article {pmid8315658, year = {1993}, author = {Hasegawa, M and Hashimoto, T and Adachi, J and Iwabe, N and Miyata, T}, title = {Early branchings in the evolution of eukaryotes: ancient divergence of entamoeba that lacks mitochondria revealed by protein sequence data.}, journal = {Journal of molecular evolution}, volume = {36}, number = {4}, pages = {380-388}, pmid = {8315658}, issn = {0022-2844}, mesh = {Amino Acid Sequence ; Animal Population Groups/classification/genetics ; Animals ; Archaea/classification/genetics ; DNA, Ribosomal/genetics ; Entamoeba/*genetics ; *Eukaryotic Cells ; Fungi/classification/genetics ; Likelihood Functions ; Mitochondria ; Peptide Elongation Factor 1 ; Peptide Elongation Factors/*genetics ; *Phylogeny ; Plants/classification/genetics ; Protozoan Proteins/*genetics ; Species Specificity ; }, abstract = {Phylogenetic analyses of ribosomal RNA sequences have played an important role in the study of early evolution of life. However, Loomis and Smith suggested that the ribosomal RNA tree is sometimes misleading--especially when G+C content differs widely among lineages--and that a protein tree from amino acid sequences may be more reliable. In this study, we analyzed amino acid sequence data of elongation factor-1 alpha by a maximum likelihood method to clarify branching orders in the early evolution of eukaryotes. Contrary to Sogin et al.'s tree of small-subunit ribosomal RNA, a protozoan species, Entamoeba histolytica, that lacks mitochondria was shown to have diverged from the line leading to eukaryotes with mitochondria before the latter separated into several kingdoms. This indicates that Entamoeba is a living relic of the earliest phase of eukaryotic evolution before the symbiosis of protomitochondria occurred. Furthermore, this suggests that, among eukaryotic kingdoms with mitochondria, Fungi is the closest relative of Animalia, and that a cellular slime mold, Dictyostelium discoideum, had not diverged from the line leading to Plantae-Fungi-Animalia before these three kingdoms separated.}, } @article {pmid8510168, year = {1993}, author = {Mebazaa, A and Martin, LD and Robotham, JL and Maeda, K and Gabrielson, EW and Wetzel, RC}, title = {Right and left ventricular cultured endocardial endothelium produces prostacyclin and PGE2.}, journal = {Journal of molecular and cellular cardiology}, volume = {25}, number = {3}, pages = {245-248}, doi = {10.1006/jmcc.1993.1031}, pmid = {8510168}, issn = {0022-2828}, mesh = {Animals ; Cells, Cultured ; Dinoprostone/*biosynthesis ; Endocardium/cytology/*metabolism ; Endothelium, Vascular/cytology/*metabolism ; Epoprostenol/*blood ; Female ; Sheep ; Ventricular Function, Left/*physiology ; Ventricular Function, Right/*physiology ; }, abstract = {The endothelium profoundly affects subjacent vascular smooth muscle function. An analogous relationship between endothelial endocardial cells (EEC) and the myocardium is suggested by Brutsaert et al.'s observation that EEC modulate the contractility of subjacent myocardium. Prostanoids are a major product by which vascular endothelium affects smooth muscle, but similar prostanoid production by EEC has not been described. To determine whether both right and left ventricular EEC produce prostacyclin (PGI2) and prostaglandin E2 (PGE2), ovine EEC were cultured. EEC prostanoid production was measured under basal conditions and after stimulation with arachidonic acid or calcium ionophore A23187. EEC from both ventricles demonstrated sustained prostacyclin and PGE2 production. Prostacyclin production was 10 times greater than PGE2. These results suggest that endocardial prostanoid production could act both locally, to modulate platelet and myocardial function, and distally, on downstream vascular tone.}, } @article {pmid8477285, year = {1993}, author = {Spitzer, RL and Stunkard, A and Yanovski, S and Marcus, MD and Wadden, T and Wing, R and Mitchell, J and Hasin, D}, title = {Binge eating disorder should be included in DSM-IV: a reply to Fairburn et al.'s "the classification of recurrent overeating: the binge eating disorder proposal".}, journal = {The International journal of eating disorders}, volume = {13}, number = {2}, pages = {161-169}, pmid = {8477285}, issn = {0276-3478}, mesh = {Anorexia Nervosa/classification/diagnosis/psychology ; Bulimia/*classification/diagnosis/psychology ; Humans ; Hyperphagia/*classification/diagnosis/psychology ; *Psychiatric Status Rating Scales ; }, abstract = {Extensive recent research supports a proposal that a new eating disorder, binge eating disorder (BED), be included in DSM-IV. BED criteria define a relatively pure group of individuals who are distressed by recurrent binge eating who do not exhibit the compensatory features of bulimia nervosa. This large number of patients currently can only be diagnosed as eating disorder not otherwise specified (EDNOS). Recognizing this new disorder will help stimulate research and clinical programs for these patients. Fairburn et al.'s critique of BED fails to acknowledge the large body of knowledge that indicates that BED represents a distinct and definable subgroup of eating disordered patients and that the diagnosis provides useful information about psychopathology, prognosis, and outcome (Fairburn, Welch, & Hay [in press]. The classification of recurrent overeating: The "binge eating disorder" proposal. International Journal of Eating Disorders.) Against any reasonable standard for adding a new diagnosis to DSM-IV, BED meets the test.}, } @article {pmid8350610, year = {1993}, author = {Casagrande, G and Viviani, F}, title = {Somatotype of Italian rugby players.}, journal = {The Journal of sports medicine and physical fitness}, volume = {33}, number = {1}, pages = {65-69}, pmid = {8350610}, issn = {0022-4707}, mesh = {Adult ; Football/*physiology ; Humans ; Italy ; Male ; *Somatotypes ; }, abstract = {Our aim was to collect lacking first-hand data on Italian rugby players. The Heath/Carter anthropometric somatotype method was applied to 28 "A" League performers (RP) aged 25 +/- 3.9 years of age. Their somatotypes and dimensions were compared with those found in previous studies on athletes involved in the same sporting activity, with data collected on 25 "sedentary" young Italians, and with Bailey et al.'s study on Canadians (1982). On average, the RP group resulted as being endomorphic mesomorphs (3.1 +/- 1.1 - 5.6 +/- 1.3 - 1.4 +/- 1.1), a result that is congruent with international data. They differed significantly from the balanced mesomorph CG (2.3 +/- 1.0 - 4.5 +/- 1.2 - 2.5 +/- 1.4) for all the measurements taken, apart from bi-epycondylar width. The peculiar somatotype scores found are congruent with the needs of rugby, an aerobic-anaerobic discipline which requires performers with great muscular power associated with a capacity to furnish energy, mainly through the anaerobic metabolism.}, } @article {pmid8451149, year = {1993}, author = {Fudin, R}, title = {Comments on Hudesman, Page, and Rautiainen's (1992) subliminal psychodynamic activation experiment.}, journal = {Perceptual and motor skills}, volume = {76}, number = {1}, pages = {41-42}, doi = {10.2466/pms.1993.76.1.41}, pmid = {8451149}, issn = {0031-5125}, mesh = {*Achievement ; Adult ; Cognition ; Female ; Humans ; Learning ; Male ; Students/psychology ; *Subliminal Stimulation ; }, abstract = {Hudesman, et al.'s (1992) contention that their finding and those of Ariam (1979), Parker (1982), and Cook (1985) show that subliminal psychodynamic activation (SPA) can improve academic performance is questioned. Results obtained from experiments using methodological innovations (Fudin, 1986) would allow a clearer interpretation of positive SPA outcomes.}, } @article {pmid8449657, year = {1993}, author = {Marchette, L and Box, N and Hennessy, M and Wasserlauf, M and Arnall, B and Copeland, D and Habib, K}, title = {Nurses' perceptions of the support of patient autonomy in do-not-resuscitate (DNR) decisions.}, journal = {International journal of nursing studies}, volume = {30}, number = {1}, pages = {37-49}, doi = {10.1016/0020-7489(93)90091-8}, pmid = {8449657}, issn = {0020-7489}, mesh = {Adult ; Aged ; Attitude of Health Personnel ; Consensus ; Decision Support Techniques ; Ethics Committees, Clinical ; Female ; Florida ; Hospitals, Private ; Hospitals, Veterans ; Humans ; Male ; Middle Aged ; Nursing Methodology Research ; Nursing Staff, Hospital/*psychology ; *Patient Advocacy ; *Personal Autonomy ; *Resuscitation Orders ; *Role ; Surveys and Questionnaires ; }, abstract = {This replication of Ott's study [Ott, B. (1986). An Ethical Problem Facing Nurses: The Support of Patient Autonomy in the Do Not Resuscitate Decision. University Microfilms International, Dissertation, Texas Women's University] and McLaughlin et al.'s study [McLaughlin, T., Brown, O. and Herman, J. (1988). Nurses' Perception of the Support of Patient Autonomy in Do Not Resuscitate Situations. Unpublished Research Report] explored hospital staff nurses' perceptions of their role in supporting patient autonomy in the do-not-resuscitate (DNR) decision. One-hundred and sixty-five registered nurses (RNs) participated: 93 from the Veterans Administration Medical Center and 72 from a private non-profit hospital. Ott's questionnaire had four hypothetical cases in which a DNR decision would probably be made with three questions about whose opinion would most support patient autonomy and whose opinion would actually be regarded as the most appropriate for making the DNR decision. Seventy per cent of perceptions of the person whose decision would be best able to support the patient's autonomy in the DNR decision and 51% of the people perceived to actually be deemed most appropriate to make the DNR decision were consistent with Ott's DNR Decision Model.}, } @article {pmid8445133, year = {1993}, author = {Johnson, JH and Turner, CW and Zwislocki, JJ and Margolis, RH}, title = {Just noticeable differences for intensity and their relation to loudness.}, journal = {The Journal of the Acoustical Society of America}, volume = {93}, number = {2}, pages = {983-991}, doi = {10.1121/1.405404}, pmid = {8445133}, issn = {0001-4966}, support = {NS24255/NS/NINDS NIH HHS/United States ; }, mesh = {Acoustic Stimulation ; Acoustics ; Adult ; Auditory Perception ; Female ; Humans ; *Loudness Perception ; Male ; Noise ; }, abstract = {The present study examines the relation between the form of the loudness function and the size of the intensity just noticeable difference (jnd). The hypothesis that equal loudnesses at any given sound frequency yield equal-intensity jnd's was examined. In addition, Hellman et al.'s [J. Acoust. Soc. Am. 82, 448-453 (1987)] experiment, which showed that jnd's are independent of the slope of the loudness function was replicated. Threshold shifts and altered loudness-balance functions for 1-kHz tones were produced by using backgrounds of narrow- or wideband noise. The two types of background noise produced intersecting points on loudness-balance functions at which intensity jnd's were obtained. Intensity jnd's were also obtained at equal-loudness levels (corresponding to 30, 40, 50, and 60 dB SL in the unmasked ear) under each of the two noise conditions and in quiet. The results indicate that tones of equal loudness produce approximately equal jnd's and that there is no apparent relation between the slope of the loudness-balance functions and the size of the intensity jnd.}, } @article {pmid8426653, year = {1993}, author = {Chaparro, A and Stromeyer, CF and Huang, EP and Kronauer, RE and Eskew, RT}, title = {Colour is what the eye sees best.}, journal = {Nature}, volume = {361}, number = {6410}, pages = {348-350}, doi = {10.1038/361348a0}, pmid = {8426653}, issn = {0028-0836}, mesh = {Color Perception/*physiology ; Humans ; Mathematics ; *Ocular Physiological Phenomena ; Photic Stimulation ; Time Factors ; Visual Fields ; *Visual Perception ; }, abstract = {It has been argued by Watson, Barlow and Robson that the visual stimulus that humans detect best specifies the spatial-temporal structure of the receptive field of the most sensitive visual neurons. To investigate 'what the eye sees best' they used stimuli that varied in luminance alone. Because the most abundant primate retinal ganglion cells, the P cells, are colour-opponent, we might expect that a coloured pattern would also be detected well. We generalized Watson et al.'s study to include variations in colour as well as luminance. We report here that our best detected coloured stimulus was seen 5-9-fold better than our best luminance spot and 3-8-fold better than Watson's best luminance stimulus. The high sensitivity to colour is consistent with the prevalence and high colour contrast-gain of retinal P cells, and may compensate for the low chromatic contrasts typically found in natural scenes.}, } @article {pmid11537423, year = {1993}, author = {Karam, EH and Srinivasan, RS and Charles, JB}, title = {A comparison of overall mathematical models of the cardiovascular system for simulating response to orthostatic stresses.}, journal = {The Physiologist}, volume = {36}, number = {1 Suppl}, pages = {S164-5}, pmid = {11537423}, issn = {0031-9376}, mesh = {Hemorrhage/*physiopathology ; Humans ; Hypotension, Orthostatic/*physiopathology ; Lower Body Negative Pressure/*adverse effects ; *Models, Cardiovascular ; Posture ; }, abstract = {Although numerous mathematical models of the cardiovascular system (CVS) have appeared in the literature only a few of them are models of the entire system with detailed representation of the heart, the vasculature, and the control elements. Like all models of biological systems, these models vary in complexity, and most of them are stimulus- specific. Their ability to simulate with acceptable accuracy either responses over a wide range of the stimulus or responses to stimuli of similar kind has not been reported. In this paper, three mathematical models of the CVS are examined in terms of their response to different orthostatic stresses, namely, lower body negative pressure (LBNP), head-up tilt, and blood loss. The short-term orthostatic responses of the models are compared to available experimental data. The models are: (i) Croston and Fitzjerrell's for study of LBNP and head-up tilt response, (ii) Jaron et al.'s for study of +Gz response, and (iii) Pullen's for simulation of response to blood loss. We will henceforth refer to these models by the letters C, J, and P, respectively.}, } @article {pmid1454467, year = {1992}, author = {Wong, JL and Schefft, BK and Moses, JA}, title = {Comparison of empirically derived and predicted standard scores for Form II of the Luria-Nebraska Neuropsychological Battery.}, journal = {Perceptual and motor skills}, volume = {75}, number = {3 Pt 1}, pages = {731-736}, doi = {10.2466/pms.1992.75.3.731}, pmid = {1454467}, issn = {0031-5125}, mesh = {Aged ; Data Interpretation, Statistical ; Humans ; Neuropsychological Tests/*standards ; Reproducibility of Results ; }, abstract = {Until Wong, Schefft, and Moses published norms for Form II of the Luria-Nebraska Neuropsychological Battery in 1990, Golden, Purisch, and Hammeke's 1985 regression equations were the only procedure available to interpret scores on Form II of the battery. In the present study comparison of the empirically based norms with standard scores obtained via the regression equations showed that (1) the scale means and standard deviations used in the development of the regression equations indicated substantially more impairment than those obtained by Wong, et al. and (2) the standard (T) scores predicted by the regression equations consistently underestimated impairment relative to the T scores obtained directly from Wong, et al.'s empirically derived norms. Reasons for, and implications of, these findings were discussed.}, } @article {pmid1296931, year = {1992}, author = {Sierra, J and Grañena, A and Bosch, F and Carreras, E and Martí, JM and Urbano-Ispizua, A and Rovira, M and Rozman, C}, title = {Mitoxantrone and intermediate-dose cytosine arabinoside for poor-risk acute leukemias: response to treatment and factors influencing outcome.}, journal = {Hematological oncology}, volume = {10}, number = {6}, pages = {301-309}, doi = {10.1002/hon.2900100603}, pmid = {1296931}, issn = {0278-0232}, mesh = {Adolescent ; Adult ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Child ; Cytarabine/*administration & dosage ; Female ; Humans ; Leukemia/*drug therapy ; Leukemia, Myeloid, Acute/drug therapy ; Male ; Middle Aged ; Mitoxantrone/*administration & dosage ; Multivariate Analysis ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy ; Prognosis ; Remission Induction ; Risk ; Time Factors ; Treatment Outcome ; }, abstract = {Mitoxantrone (MIT, 12 mg/m2, i.v. 5 days) and intermediate-dose cytosine arabinoside (IDAC 1 g/m2/12 h, i.v. 3 days) was given to 43 patients with poor-risk acute leukemias (AL). Moderate or severe toxicity was infrequent. The proportion of complete remissions (CR) in the main patient categories was as follows: 15/18 (85 per cent) in acute myeloid leukemia (AML) in the first relapse, 2/6 in ALL in the first relapse, 0/2 in AML in relapse after bone marrow transplantation (BMT), 2/7 in AML refractory to first-line treatment (REF-AL), and 1/6 in postmyelodysplastic (PMD-AL) plus secondary AL (S-AL). The mortality rate during induction was 23 per cent. Median duration of CR was 24 weeks. The multivariate prognostic factor analysis on CR obtention showed that data concerning treatment for the first relapse and platelet count higher than the median of the series were favourable. On the contrary, PMD-AL, S-AL and REF-AL were unfavourable situations. A percentage of marrow erythroblasts superior to the median was a favourable prognostic factor for survival. Finally, the duration of CR after MIT-IDAC was directly related to the duration of previous CR. In conclusion, MIT-IDAC was highly effective to attain CR in AML in the first relapse. However, due to the poor long-term results in these patients, additional measures are recommended after CR.}, } @article {pmid1447933, year = {1992}, author = {Onslow, M and Adams, R and Ingham, R}, title = {Reliability of speech naturalness ratings of stuttered speech during treatment.}, journal = {Journal of speech and hearing research}, volume = {35}, number = {5}, pages = {994-1001}, doi = {10.1044/jshr.3505.994}, pmid = {1447933}, issn = {0022-4685}, support = {1 ROI DC00060-01A1/DC/NIDCD NIH HHS/United States ; }, mesh = {Adult ; Female ; Humans ; Male ; Speech/*physiology ; Speech Perception ; Speech Therapy ; Stuttering/*therapy ; }, abstract = {This study evaluated the reliability with which relatively sophisticated and unsophisticated judges used a 9-point scale to rate the speech naturalness of speech samples from 10 clients in a treatment program for stuttering that employed prolonged speech. Judges rated repeated speech samples from different speakers during various phases of the program. Different groups of sophisticated and unsophisticated judges made ratings at either 15 sec, 30 sec, or 60 sec intervals while listening to the samples. Of the reliability indices, intraclass correlations were significantly higher for sophisticated judges although the consistency and agreement of unsophisticated judges were generally equivalent to that of sophisticated judges. Both agreement scores and intraclass correlations were higher when ratings were made at 60 sec rather than 30 sec intervals. The predominant variable that influenced judgement reliability appeared to be differences among the subjects. The methodology partially replicated Martin, Haroldson, and Triden's (1984) initial investigation on the use of this scale. However, the levels of intra- or interjudge reliability in this study were lower than the levels achieved by Martin et al.'s judges. There were important differences between the Martin et al. study and this one that may account for the findings, and these are discussed.}, } @article {pmid1453973, year = {1992}, author = {LeCompte, DC}, title = {In search of a strong visual recency effect.}, journal = {Memory & cognition}, volume = {20}, number = {5}, pages = {563-572}, pmid = {1453973}, issn = {0090-502X}, support = {MH35873/MH/NIMH NIH HHS/United States ; }, mesh = {Adult ; Auditory Perception ; Cognition ; Female ; Humans ; Male ; Research Design ; *Space Perception ; *Visual Perception ; }, abstract = {When a sequence of visual stimuli is presented in a fixed location, immediate serial recall of the sequence is characterized by only a small recency effect. According to Battacchi, Pelamatti, and Umiltà (1990), the distribution of visual stimuli over space, as well as time, greatly enhances the recency effect. After an initial failure to find a strong visual recency effect with distributed presentation (Experiment 1), in the remaining experiments an attempt was made to more closely approximate Battacchi et al.'s methodology by eliminating articulatory suppression (Experiments 2-7), using their stimuli (Experiments 3-7), blocking conditions (Experiments 4-7), requiring written rather than typed responses (Experiments 5-7), and using their list length (Experiments 6 and 7). Nevertheless, even when their method was followed as closely as possible (Experiment 7), distributed presentation did not produce a strong visual recency effect. The influence of distributed presentation on the visual recency effect would seem to be, at best, limited.}, } @article {pmid1395647, year = {1992}, author = {Harris, LJ and Snyder, PJ}, title = {Subjective mood state and perception of emotion in chimeric faces.}, journal = {Cortex; a journal devoted to the study of the nervous system and behavior}, volume = {28}, number = {3}, pages = {471-481}, doi = {10.1016/s0010-9452(13)80155-4}, pmid = {1395647}, issn = {0010-9452}, mesh = {Adolescent ; Adult ; *Affect ; *Attention ; *Discrimination Learning ; *Dominance, Cerebral ; *Facial Expression ; Female ; Humans ; Male ; Neuropsychological Tests ; *Visual Perception ; }, abstract = {Levy, Heller, Banich, and Burton (1983) have shown that hemispheric activational, or arousal, style, as measured by direction and consistency of choice of the "happer face" on a free-viewing Chimeric Faces Test, is highly reliable and varies across individuals who otherwise presumably have similar cortical organization (e.g., right-handed college students). The current experiment asks whether such individual differences in hemispheric arousal style are moderated by long-term, in the sense of enduring, individual differences in mood, as measured by the Profile of Mood States (POMS) questionnaire. Like Levy et al.'s subjects, most of our subjects (126 right-handed college students) made most of their choices on the Chimeric Faces Test based on the emotional cue (the smile) positioned in the half of the face to the viewer's left, or left visual hemifield (LVH), whereas a small minority were equally consistent in making their choice based on the emotional cue positioned in the half of the face to the viewer's right, or right visual hemifield (RVH). Performance on the Chimeric Faces Test, however, proved to be unrelated to scores on the POMS questionnaire. This suggests that hemispheric arousal style, as indexed by the Chimeric Faces Test, is robust enough, for a population of normal right-handers, to transcend any differences in mood as measured by the POMS questionnaire.}, } @article {pmid1529069, year = {1992}, author = {Workman, M and Beer, J}, title = {Aggression, alcohol dependency, and self-consciousness among high school students of divorced and nondivorced parents.}, journal = {Psychological reports}, volume = {71}, number = {1}, pages = {279-286}, doi = {10.2466/pr0.1992.71.1.279}, pmid = {1529069}, issn = {0033-2941}, mesh = {Adolescent ; Aggression/*psychology ; Alcoholism/*psychology ; Divorce/*psychology ; Female ; Gender Identity ; Humans ; Male ; *Personality Development ; Personality Inventory ; Rural Population ; *Self Concept ; }, abstract = {134 high school students from a small high school in north central Kansas completed the MacAndrew Alcoholism Scale, Fenigstein, et al.'s Self-consciousness Scale, and Zaks' Aggression Scale. Analyses of variance showed significant differences between boys and girls but not among grades. On the aggression and alcohol measures boys scored higher than girls, but lower on public self-consciousness. Youth of divorced parents scored significantly higher than those of nondivorced parents on aggression, private self-consciousness, and general self-consciousness. Aggression scores were significantly and positively correlated with those on the alcohol and private self-consciousness scales. When students' alcoholism scores indicate problems with alcohol, their scores on aggression indicate greater aggression and their private self-consciousness scores indicate sensitivity toward events in their environment, then having concerns about inner self can inhibit the action required for change. MacAndrew scores correlated significantly and negatively with scores on social anxiety about self-consciousness. When MacAndrew scores indicated problems with alcohol, the students' scores on social anxiety about self-consciousness suggested confidence in social settings, being at ease interacting with people. The present study involved students from a single rural district so increased understanding will require more extensive research if strategies for prevention and intervention are to be developed and utilized.}, } @article {pmid1410554, year = {1992}, author = {Caplan, D and Rochon, E and Waters, GS}, title = {Articulatory and phonological determinants of word length effects in span tasks.}, journal = {The Quarterly journal of experimental psychology. A, Human experimental psychology}, volume = {45}, number = {2}, pages = {177-192}, doi = {10.1080/14640749208401323}, pmid = {1410554}, issn = {0272-4987}, support = {DC00776-01/DC/NIDCD NIH HHS/United States ; }, mesh = {Aged ; *Attention ; Female ; Humans ; Male ; Memory, Short-Term ; *Mental Recall ; Middle Aged ; *Phonetics ; Reading ; Speech Perception ; *Verbal Learning ; }, abstract = {Several previous studies have shown that memory span is greater for short words than for long words. This effect is claimed to occur even when the short and long words are matched for the number of syllables and phonemes and so to provide evidence for subvocal articulation as being one mechanism that underlies memory span (Baddeley, Thomson, & Buchanan, 1975). The three experiments reported in this paper further investigate the articulatory determinants of word length effects on span tasks. Experiment 1 replicated Baddeley et al.'s finding of an effect of word length on auditory and visual span when the stimuli consist of words that differ in terms of the number of syllables. Experiments 2 and 3 showed that the effects of word length are eliminated when the words in the span task are matched for the number of syllables and phonemes but differ with respect to the duration and/or complexity of their articulatory gestures. These results indicate that it is the phonological structure of a word and not features of its actual articulation that determines the magnitude of the word length effect in span tasks.}, } @article {pmid1583225, year = {1992}, author = {Swann, WB and Wenzlaff, RM and Tafarodi, RW}, title = {Depression and the search for negative evaluations: more evidence of the role of self-verification strivings.}, journal = {Journal of abnormal psychology}, volume = {101}, number = {2}, pages = {314-317}, doi = {10.1037//0021-843x.101.2.314}, pmid = {1583225}, issn = {0021-843X}, support = {MH 00498/MH/NIMH NIH HHS/United States ; MH 37598/MH/NIMH NIH HHS/United States ; }, mesh = {Adult ; Depression/diagnosis/*psychology ; *Feedback ; Female ; Humans ; *Interpersonal Relations ; Male ; Motivation ; *Self Concept ; Social Environment ; }, abstract = {Swann, Wenzlaff, Krull, and Pelham (1992) suggested that depressed and dysphoric persons verify their self-conceptions by seeking rather negative appraisals. Hooley and Richters (1992) and Alloy and Lipman (1992) have worried that (a) idiosyncratic features of Swann et al.'s participants and design may have produced their effects and (b) Swann et al. presented no evidence that self-verification strivings are motivated. We address these issues empirically. Study 1 showed that 20 dysphoric participants preferred interacting with a person who appraised them unfavorably over participating in another study, in comparison with 30 nondysphorics. Study 2 revealed that 26 dysphoric persons responded to feedback that challenged their negative self-view by working to reaffirm their low self-esteem, in comparison with 47 nondysphorics. These findings support the notion that at some level depressed and dysphoric persons want rather negative appraisals.}, } @article {pmid1602078, year = {1992}, author = {Hawks, JH}, title = {Empowerment in nursing education: concept analysis and application to philosophy, learning and instruction.}, journal = {Journal of advanced nursing}, volume = {17}, number = {5}, pages = {609-618}, doi = {10.1111/j.1365-2648.1992.tb02840.x}, pmid = {1602078}, issn = {0309-2402}, mesh = {Decision Making ; Education, Nursing/methods/organization & administration/*standards ; Humans ; Learning ; Models, Nursing ; Organizational Objectives ; *Philosophy, Nursing ; *Power, Psychological ; Problem Solving ; Teaching/methods/standards ; }, abstract = {The Walker & Avant strategy is used to complete a concept analysis of empowerment. Empowerment is defined as the interpersonal process of providing the proper tools, resources and environment to build, develop and increase the ability and effectiveness of others to set and reach goals for individual and social ends. Empowerment occurs between two or more people: the person who empowers and the person(s) who is (are) empowered. The Murrell-Armstrong Empowerment matrix, with six categories of empowering behaviours, provides the theoretical framework. References from organizational, nursing, educational and sociological literature provide support for the defining attributes, antecedents and consequences of empowerment. A conceptual map depicts these relationships and demonstration cases serve to make the ideas more apparent. The concept of empowerment is applied to philosophy, learning and instruction. Pragmatism reflects the ideas presented on empowerment because both embrace individual and social goals, the student is active in the learning process, learning is lifelong, and the appropriate environment, tools and resources for learning must be present. Kolb's experimental learning model corresponds with empowerment and pragmatism. The works of Dewey, Lewin, Piaget, Rogers and Freire are used as the basis for the model. Kolb describes learning as a four-step process that includes concrete experience, reflective observation, abstract conceptualization and active experimentation. Transformative instruction is based on Freire's critical pedagogy, Belenky et al.'s connected teaching, Schön's reflection-in-action, and activities that allow students to complete the experimental learning cycle. Several strategies that promote transformative instruction are discussed.}, } @article {pmid1583224, year = {1992}, author = {Alloy, LB and Lipman, AJ}, title = {Depression and selection of positive and negative social feedback: motivated preference or cognitive balance?.}, journal = {Journal of abnormal psychology}, volume = {101}, number = {2}, pages = {310-313}, pmid = {1583224}, issn = {0021-843X}, mesh = {Adult ; Depression/diagnosis/*psychology ; *Feedback ; Female ; Humans ; Internal-External Control ; *Interpersonal Relations ; Male ; *Motivation ; *Self Concept ; Social Environment ; }, abstract = {In this commentary we examine Swann, Wenzlaff, Krull, and Pelham's (1992) findings with respect to each of 5 central propositions in self-verification theory. We conclude that although the data are consistent with self-verification theory, none of the 5 components of the theory have been demonstrated convincingly as yet. Specifically, we argue that depressed subjects' selection of social feedback appears to be balanced or evenhanded rather than biased toward negative feedback and that there is little evidence to indicate that depressives actively seek negative appraisals. Furthermore, we suggest that the studies are silent with respect to the motivational postulates of self-verification theory and that a variety of competing cognitive and motivational models can explain Swann et al.'s findings as well as self-verification theory.}, } @article {pmid1735316, year = {1992}, author = {Saclarides, TJ and Rohrer, DA and Bhattacharyya, AK and Bapna, MS}, title = {Effect of intraoperative radiation on the tensile strength of small bowel anastomoses.}, journal = {Diseases of the colon and rectum}, volume = {35}, number = {2}, pages = {151-157}, doi = {10.1007/BF02050670}, pmid = {1735316}, issn = {0012-3706}, mesh = {Anastomosis, Surgical ; Animals ; Ileum/pathology/physiopathology/*radiation effects/*surgery ; In Vitro Techniques ; Intraoperative Period ; Radiation Injuries, Experimental/pathology/physiopathology ; Rats ; Rats, Inbred Strains ; Tensile Strength/radiation effects ; }, abstract = {Increasing interest in the use of preoperative or intraoperative radiation therapy for cancer has led to concerns regarding tissue healing and integrity subsequent to treatment. This is especially so for intestinal anastomoses incorporating irradiated bowel, where poor healing may lead to anastomotic disruption and sepsis. One hundred thirty Sprague-Dawley rats were randomized into five groups as follows: both limbs, one limb, or neither limb of an anastomosis received 2,000 R of radiation intraoperatively. A fourth group had a segment of small bowel irradiated, with no anastomosis; a fifth group had the gut exposed by celiotomy. The control groups and all anastomoses underwent tensile strength measurements on the seventh postoperative day, with findings as follows: no anastomosis, no irradiation, 143.75 g; no anastomosis, irradiated, 114.50 g; anastomosis, no irradiation, 85.273 g; anastomosis, one limb irradiated, 78.100 g; anastomosis, both limbs irradiated, 59.00 g. There was no statistical difference in tensile strength of the anastomosis between when neither limb and when just one limb was irradiated. However, when both limbs were irradiated, the loss of strength was statistically significant (P = 0.002). Irradiation damage scores were assigned using Black et al.'s histologic scoring system. These scores were not significantly different between the irradiated segments. Inflammation and fibrosis scores for the anastomoses were also not significantly different. These results indicate that, in rats, anastomotic healing is impaired only when both limbs of the anastomosed intestine are irradiated. The normal strength of the anastomosis with only one limb irradiated cannot be explained by differences in inflammation, fibrosis, or radiation damage and is caused by an undetermined factor.}, } @article {pmid1545321, year = {1992}, author = {Walker, LS and Zeman, JL}, title = {Parental response to child illness behavior.}, journal = {Journal of pediatric psychology}, volume = {17}, number = {1}, pages = {49-71}, doi = {10.1093/jpepsy/17.1.49}, pmid = {1545321}, issn = {0146-8693}, support = {HD2364/HD/NICHD NIH HHS/United States ; }, mesh = {*Adaptation, Psychological ; Adolescent ; Child ; Female ; Humans ; Male ; Parenting/*psychology ; Personality Assessment ; Personality Development ; Reinforcement, Psychology ; *Sick Role ; *Socialization ; }, abstract = {Examined the effects of child age and gender, parent gender, and type of child illness on parents' responses to their children's illness behavior. Study 1 describes the development of the Illness Behavior Encouragement Scale, based on Whitehead et al.'s Social Learning Scales for adults, and provides evidence supporting symptom specificity in children's learning of illness behavior. Results of Study 2 indicate that mothers encourage children's illness behavior more than fathers, that parents encourage children to adopt the sick role for gastrointestinal symptoms more than for cold symptoms, and that girls perceive parents as encouraging their illness behavior more than boys, that is, girls report receiving more sympathy and being allowed more relief from responsibility during illness episodes than boys.}, } @article {pmid1545172, year = {1992}, author = {Jinno, M and Osawa, Y and Sugimura, K and Kobayashi, T and Kitamura, S and Iwata, S and Akaboshi, K and Nozawa, S}, title = {[Importance of sperm morphology assessment in human in vitro fertilization].}, journal = {Nihon Sanka Fujinka Gakkai zasshi}, volume = {44}, number = {2}, pages = {203-207}, pmid = {1545172}, issn = {0300-9165}, mesh = {Abortion, Spontaneous ; Female ; *Fertilization in Vitro ; Humans ; Male ; Pregnancy ; Risk Factors ; Sperm Count ; Sperm Head ; Sperm Motility/physiology ; Sperm-Ovum Interactions ; Spermatozoa/*cytology/physiology ; }, abstract = {Two hundred eighteen IVF cycles were analyzed in order to clarify the influence of the strictly normal morphology (SNM) of sperm on IVF outcome. SNM was defined according to Kruger et al.'s strict criteria (1988) with our modifications. IVF cycles were divided into 3 groups: %SNM greater than or equal to 40% (69 cycles), 40% less than %SNM greater than or equal to 12% (123 cycles) and %SNM less than 12% (26 cycles). The rates of embryo transfer and pregnancy per cycle and the rate of abortion per pregnancy in the three groups were as follows: 81%, 39%, 19% in %SNM greater than or equal to 40%; 71%, 24%, 30% in 40% greater than %SNM greater than or equal to 12%; and 58%, 7.7%, 50% in %SNM less than 12%. The pregnancy rate per cycle significantly decreased as the %SNM decreased (p less than 0.01), and there was a tendency toward an increase in the abortion rate per pregnancy as the %SNM decreased. The results suggest that %SNM is a useful parameter to use in predicting the IVF outcome.}, } @article {pmid11538397, year = {1992}, author = {Toon, OB and McKay, CP and Griffith, CA and Turco, RP}, title = {A physical model of Titan's aerosols.}, journal = {Icarus}, volume = {95}, number = {1}, pages = {24-53}, doi = {10.1016/0019-1035(92)90188-d}, pmid = {11538397}, issn = {0019-1035}, mesh = {*Atmosphere ; *Dust ; Ethane/analysis ; *Extraterrestrial Environment ; Hydrocarbons/analysis ; Mathematics ; Methane/analysis ; *Models, Theoretical ; Optics and Photonics ; Particle Size ; Photochemistry ; *Saturn ; Temperature ; }, abstract = {Microphysical simulations of Titan's stratospheric haze show that aerosol microphysics is linked to organized dynamical processes. The detached haze layer may be a manifestation of 1 cm sec-1 vertical velocities at altitudes above 300 km. The hemispherical asymmetry in the visible albedo may be caused by 0.05 cm sec-1 vertical velocities at altitudes of 150 to 200 km, we predict contrast reversal beyond 0.6 micrometer. Tomasko and Smith's (1982, Icarus 51, 65-95) model, in which a layer of large particles above 220 km altitude is responsible for the high forward scattering observed by Rages and Pollack (1983, Icarus 55, 50-62), is a natural outcome of the detached haze layer being produced by rising motions if aerosol mass production occurs primarily below the detached haze layer. The aerosol's electrical charge is critical for the particle size and optical depth of the haze. The geometric albedo, particularly in the ultraviolet and near infrared, requires that the particle size be near 0.15 micrometer down to altitudes below 100 km, which is consistent with polarization observations (Tomasko and Smith 1982, West and Smith 1991, Icarus 90, 330-333). Above about 400 km and below about 150 km Yung et al.'s (1984, Astrophys. J. Suppl. Ser. 55, 465-506) diffusion coefficients are too small. Dynamical processes control the haze particles below about 150 km. The relatively large eddy diffusion coefficients in the lower stratosphere result in a vertically extensive region with nonuniform mixing ratios of condensable gases, so that most hydrocarbons may condense very near the tropopause rather than tens of kilometers above it. The optical depths of hydrocarbon clouds are probably less than one, requiring that abundant gases such as ethane condense on a subset of the haze particles to create relatively large, rapidly removed particles. The wavelength dependence of the optical radius is calculated for use in analyzing observations of the geometric albedo. The lower atmosphere and surface should be visible outside of regions of methane absorption in the near infrared. Limb scans at 2.0 micrometers wavelength should be possible down to about 75 km altitude.}, } @article {pmid1610083, year = {1992}, author = {Partensky, C and Miranda, F and Berger, F and Moulinier, B}, title = {[Esophagectomy without thoracotomy for adenocarcinoma in Barrett's esophagus].}, journal = {Annales de chirurgie}, volume = {46}, number = {4}, pages = {303-308}, pmid = {1610083}, issn = {0003-3944}, mesh = {Adenocarcinoma/diagnostic imaging/etiology/pathology/*surgery ; Aged ; Barrett Esophagus/complications/diagnostic imaging/*surgery ; Esophageal Neoplasms/diagnostic imaging/etiology/pathology/*surgery ; Esophagectomy/*methods ; Humans ; Male ; Middle Aged ; Postoperative Complications ; Tomography, X-Ray Computed ; Ultrasonography ; }, abstract = {From April 1985 to November 1990, 12 patients with adenocarcinoma in a Barrett's esophagus, all of them men, with a median age of 62 years (range, 46 to 79 years), were operated by transhiatal esophagectomy and were submitted to a periodic follow-up. Dysphagia was the main symptom. Preoperative investigations included esogastroscopy and CT-scan of the abdomen and thorax in all patients. Esophageal endosonography was performed in the last 4 cases and MRI in one case. All patients recovered postoperatively and were discharged from hospital. The resected specimens were staged according to Rosenberg et al.'s classification: stage 1, 3 patients, stage 2, 2 patients, stage 3, 6 patients, stage 4, 1 patient. An anastomotic stricture occurred in 4 patients and was treated successfully by endoscopic dilatation. Five patients died during the follow-up period. Seven patients are alive without evidence of recurrence. Transhiatal esophagectomy appears to be the procedure of choice for adenocarcinoma arising from Barrett's esophagus.}, } @article {pmid1546116, year = {1992}, author = {Greene, SB}, title = {Multiple explanations for multiply quantified sentences: are multiple models necessary?.}, journal = {Psychological review}, volume = {99}, number = {1}, pages = {184-7; discussion 188-90}, doi = {10.1037/0033-295x.99.1.184}, pmid = {1546116}, issn = {0033-295X}, support = {MH39633/MH/NIMH NIH HHS/United States ; }, mesh = {*Attention ; *Concept Formation ; Humans ; Pattern Recognition, Visual ; *Problem Solving ; }, abstract = {Johnson-Laird, Byrne, and Tabossi (1989) presented a theory of deductive reasoning for inference problems using multiply quantified premises (e.g., "All of the squares are connected to some of the circles"). Their theory classifies such problems into those that require subjects to construct only 1 mental model and those that require multiple models. They presented data that corroborate the theory. This article shows that Johnson-Laird et al.'s major results can be explained without invoking mental models or, in fact, deductive reasoning at all. Furthermore, it is demonstrated that, contrary to the assumption of these authors, reversing the order of the quantifiers in a multiply quantified sentence may produce a sentence that is both more difficult to comprehend and more ambiguous. Finally, some implications for theories of how people understand multiply quantified sentences are noted.}, } @article {pmid1488790, year = {1992}, author = {Westefeld, JS and Cardin, D and Deaton, WL}, title = {Development of the College Student Reasons for Living Inventory.}, journal = {Suicide & life-threatening behavior}, volume = {22}, number = {4}, pages = {442-452}, pmid = {1488790}, issn = {0363-0234}, mesh = {Adult ; Ambulatory Care ; Female ; Humans ; Male ; Malpractice/economics ; Mental Disorders/*therapy ; Mental Health Services/organization & administration/standards ; Professional-Patient Relations ; Psychotherapy ; Suicide, Attempted/*prevention & control ; Workforce ; }, abstract = {Two studies were carried out in an effort to develop and evaluate an instrument designed to assess suicidal risk in college students. Study 1 describes the development of the College Student Reasons for Living Inventory (CSRLI), an instrument that measures the extent to which college students place importance on various reasons for living even when contemplating suicide. The impetus for the current study was provided by Linehan et al., who in 1983 developed the Reasons for Living Inventory for use with adults. In the current study college students generated a series of 84 "reasons for living" items, which were reduced through factor analysis to a final inventory of 46 items. Six factors were extracted as follows: Survival and Coping Beliefs, College and Future-Related Concerns, Moral Objections, Responsibility to Friends and Family, Fear of Suicide, and Fear of Social Disapproval. Five of these factors reflect the same basic themes contained in the Linehan et al. (1983) study. The sixth factor (College and Future-Related Concerns) appears to be unique to college students. Linehan et al.'s Child-Related Concerns factor expectedly did not appear in this college sample. In Study 2 initial evaluation of the CSRLI was carried out through the use of correlational, confirmatory factor, and discriminant analyses. Results indicate that the CSRLI holds promise as an instrument to predict suicidal risk among college students.}, } @article {pmid1295269, year = {1992}, author = {McCulloch, BJ}, title = {Gender and race: an interaction affecting the replicability of well-being across groups.}, journal = {Women & health}, volume = {19}, number = {4}, pages = {65-89}, doi = {10.1300/j013v19n04_05}, pmid = {1295269}, issn = {0363-0242}, support = {AG00029/AG/NIA NIH HHS/United States ; }, mesh = {Abstracting and Indexing/standards ; Black or African American/*psychology ; Aged ; Aging/*psychology ; Cultural Characteristics ; Evaluation Studies as Topic ; Factor Analysis, Statistical ; Female ; Gender Identity ; Humans ; Male ; *Models, Psychological ; *Personal Satisfaction ; Reproducibility of Results ; Sex Factors ; Socialization ; Socioeconomic Factors ; Surveys and Questionnaires/*standards ; White People/*psychology ; }, abstract = {The Life Satisfaction Index (LSI) continues to be one of the most frequently used measures of well-being in social gerontology. Discrepancies in the operational use of the LSI, however, have made comparisons across studies difficult. Few studies have incorporated examination of the effect of gender/race interactions on the performance of the LSI. The purpose of this study was to examine differences in the hierarchical factor structure of life satisfaction among four gender/race groups using previously reported item pools and coding schemes. Three second-order, three-factor life satisfaction models were examined using confirmatory factor analysis techniques with four groups of older adults: White men (n = 846), White women (n = 1341), Black men (n = 177), and Black women (n = 287). In general, results showed differences in LSI factor structure across gender/race groups. With regard to coding scheme, models using Neugarten et al.'s original coding scheme (1961) and those using Wood et al.'s alternative scoring (1969) were similar. Examination of models using different LSI item pools showed that the factor structure of life satisfaction was affected by the gender/race interaction, underscoring the problem of misspecification resulting from the sum of LSI items and use of the summated score as a unidimensional measure of well-being. Implications for future research are discussed.}, } @article {pmid1793093, year = {1991}, author = {Emery, RE}, title = {Mediational screening in theory and in practice.}, journal = {American journal of community psychology}, volume = {19}, number = {6}, pages = {853-857}, doi = {10.1007/BF00937886}, pmid = {1793093}, issn = {0091-0562}, mesh = {Causality ; Child ; Child Reactive Disorders/epidemiology/prevention & control/psychology ; Clinical Trials as Topic ; Divorce ; Health Services Research ; *Health Status Indicators ; Humans ; Mass Screening/economics/*standards ; Mental Health Services/*standards ; Preventive Health Services/*standards ; Sensitivity and Specificity ; Treatment Outcome ; }, abstract = {Pillow et al.'s (1991) argument for mediational selection omits discussion of what may be the strategy's greatest advantage, the early identification of risk. The theoretical benefits to prevention of identifying developmental processes are briefly noted here. At the same time, practical limitations of mediational selection are noted, particularly in relation to establishing and interpreting the correlation found between mediational and outcome variables. It is concluded that mediational selection is one, but only one, selection strategy worthy of consideration in prevention research.}, } @article {pmid1961811, year = {1991}, author = {Keane, MC and Morgan, BS}, title = {Perceived self-efficacy and language differences.}, journal = {Psychological reports}, volume = {69}, number = {1}, pages = {291-298}, doi = {10.2466/pr0.1991.69.1.291}, pmid = {1961811}, issn = {0033-2941}, mesh = {*Acculturation ; Humans ; *Language ; Personality Development ; Personality Inventory ; *Self Concept ; Students, Nursing/*psychology ; }, abstract = {The relationship between language differences and perceived self-efficacy was examined for two different classes (ns = 89 and 66) of a linguistically diverse nursing student population. Sherer, et al.'s General Self-efficacy Scale was factor analyzed, producing two factors (subscales) labeled Tendency to Avoid/Give Up and Tendency to Persist. Students who were nonprimary speakers of English were more likely to avoid difficult tasks or give up because they believed they would fail than those students who were primary speakers of English. There were no significant differences between the groups on Tendency to Persist. Also, students' class level in the program was not related to self-efficacy.}, } @article {pmid1889017, year = {1991}, author = {Gauthier, JG and Ricard, S and Morin, BA and Dufour, L and Brodeur, JM}, title = {[Adolescents' fear of dental treatment: development and evaluation of a cognitive inventory].}, journal = {Journal (Canadian Dental Association)}, volume = {57}, number = {8}, pages = {658-662}, pmid = {1889017}, issn = {0709-8936}, mesh = {Adolescent ; *Adolescent Behavior ; Anxiety/diagnosis ; Cognitive Behavioral Therapy ; Dental Care/*psychology ; Factor Analysis, Statistical ; Fear ; Female ; Humans ; Male ; Manifest Anxiety Scale/*statistics & numerical data ; Reproducibility of Results ; Surveys and Questionnaires ; }, abstract = {Morin et al.'s Inventaire cognitif de la peur des traitements dentaires pour adolescent(e)s [Adolescents' Fear of Dental Treatment Cognitive Inventory] was administered to 343 subjects. Factor analysis revealed a single general factor that accounted for 33.5 per cent of the total variance. A reliability test revealed an alpha coefficient of 0.91, which was quite acceptable. A measure of test-retest reliability over a four-week period (N = 181) indicated that the scale was stable over time (r = 0.85). Standard error of measurement was found to be 4.63. Normative data are provided along with a description of the final version of the scale.}, } @article {pmid17014783, year = {1991}, author = {Fraaije, JG and Murris, RM and Norde, W and Lyklema, J}, title = {Interfacial thermodynamics of protein adsorption, ion co-adsorption and ion binding in solution. I. Phenomenological linkage relations for ion exchange in lysozyme chromatography and titration in solution.}, journal = {Biophysical chemistry}, volume = {40}, number = {3}, pages = {303-315}, doi = {10.1016/0301-4622(91)80028-p}, pmid = {17014783}, issn = {0301-4622}, abstract = {In this paper we discuss the thermodynamics of ion binding in solution, protein adsorption and ion co-adsorption. The emphasis is on charge regulation effects. To this end, we introduce phenomenological linkage relations from which the ion binding can be calculated from the electrolyte dependency of proton titration curves and the co-adsorption from the electrolyte dependency of protein adsorption isotherms. The linkage relations are derived from classical interfacial thermodynamics, and thus offer an alternative approach as compared to the mass balance equations which are currently used in biotechnology, and Record et al.'s 1978 analysis of Wyman's Binding Polynomial for protein interactions. The co-adsorption theory is an extension of our previous analysis of ion binding in solution, which we include here for comparison of the ion co-adsorption with the ion binding in solution. The theory is applied to the chromatography of lysozyme on the strong cation exchanger 'mono S' and to the proton titration of lysozyme in solution. In the accompanying Part 2 of this paper the results are interpreted with a simple model.}, } @article {pmid1745727, year = {1991}, author = {Näätänen, R}, title = {Mismatch negativity outside strong attentional focus: a commentary on Woldorff et al. (1991).}, journal = {Psychophysiology}, volume = {28}, number = {4}, pages = {478-484}, doi = {10.1111/j.1469-8986.1991.tb00735.x}, pmid = {1745727}, issn = {0048-5772}, mesh = {Arousal/*physiology ; Attention/*physiology ; *Electroencephalography ; Evoked Potentials, Auditory/physiology ; Humans ; Pitch Discrimination/*physiology ; Psychophysiology ; }, abstract = {Several previous papers have suggested that the mismatch negativity (MMN), an event-related potential (ERP) component specific to stimulus change after repetition, is fully automatic, that is, not affected by attention. Woldorff, Hackley, and Hillyard (1991), however, report that the MMN elicited by an intensity decrement of a repeating stimulus is considerably attenuated when attention is strongly focused on other stimuli. The present commentary attributes most of this effect to attention effects on ERP components other than the MMN but also admits that some attentional reduction of the MMN component indeed occurred. This attenuation was interpreted by Woldorff et al. as indicating suppression of early sensory processing in unattended channels, but this is contraindicated by some very recent data from the present author's laboratory and elsewhere showing that the MMN to frequency change is not attenuated outside a strong attentional focus. Consequently, an alternative explanation is proposed for Woldorff et al.'s important finding.}, } @article {pmid2035524, year = {1991}, author = {Pericak-Vance, MA and Bebout, JL and Gaskell, PC and Yamaoka, LH and Hung, WY and Alberts, MJ and Walker, AP and Bartlett, RJ and Haynes, CA and Welsh, KA}, title = {Linkage studies in familial Alzheimer disease: evidence for chromosome 19 linkage.}, journal = {American journal of human genetics}, volume = {48}, number = {6}, pages = {1034-1050}, pmid = {2035524}, issn = {0002-9297}, support = {AG05128/AG/NIA NIH HHS/United States ; AG07922/AG/NIA NIH HHS/United States ; P01-NS-26630/NS/NINDS NIH HHS/United States ; }, mesh = {Age Factors ; Aged ; Aged, 80 and over ; Alzheimer Disease/*genetics ; Chromosome Mapping ; *Chromosomes, Human, Pair 19 ; DNA/genetics ; *Genetic Linkage ; Humans ; Lod Score ; Middle Aged ; Pedigree ; }, abstract = {A genetic component in the etiology of Alzheimer disease (AD) has been supported by indirect evidence for several years, with autosomal dominant inheritance with age-dependent penetrance being suggested to explain the familial aggregation of affecteds. St. George Hyslop et al. reported linkage of familial AD (FAD) in four early-onset families (mean age at onset [M] less than 50 years). Subsequent studies have been inconsistent in their results; Goate et al. also reported positive lod scores. However, both Pericak-Vance et al.'s study of a series of mainly late-onset FAD families (M greater than 60 years) and Schellenberg et al.'s study failed to confirm linkage to chromosome 21 (CH21). These various studies suggest the possibility of genetic heterogeneity, with some families linked to CH21 and others unlocalized. Recently, St. George Hyslop et al. extended their analysis to include additional families. The extended analyses supported their earlier finding of linkage to CH21, while showing strong evidence of heterogeneity between early-onset (M less than 65 years) and late-onset (M greater than 60 years) FAD families. Because our families did not show linkage to CH21, we undertook a genomic search for an additional locus for FAD. Because of both the confounding factor of late age at onset of FAD and the lack of clear evidence of Mendelian transmission in some of our families, we employed the affected-pedigree-member (APM) method of linkage analysis as an initial screen for possible linkage. Using this method, we identified two regions suggesting linkage: the proximal long arm of chromosome 19 (CH19) and the CH21 region of FAD linkage reported by St. George Hyslop et al. Application of standard likelihood (LOD score) analysis to these data support the possibility of an FAD gene locate on CH19, particularly in the late-onset FAD families. These data further suggest genetic heterogeneity and delineate this region of CH19 as an area needing additional investigation in FAD.}, } @article {pmid1864813, year = {1991}, author = {Chen, PY and Spector, PE}, title = {Negative affectivity as the underlying cause of correlations between stressors and strains.}, journal = {The Journal of applied psychology}, volume = {76}, number = {3}, pages = {398-407}, doi = {10.1037/0021-9010.76.3.398}, pmid = {1864813}, issn = {0021-9010}, mesh = {Adolescent ; Adult ; Aged ; Anxiety/*psychology ; Depression/*psychology ; Female ; Humans ; *Job Satisfaction ; Male ; Middle Aged ; Occupational Diseases/*psychology ; Risk Factors ; Somatoform Disorders/*psychology ; Stress, Psychological/*complications ; }, abstract = {The extent to which negative affectivity (NA), the tendency to experience a wide range of negative emotions, inflated correlations between chronic job stressors and strains was examined in this study. NA was found to account for a large proportion of shared variance between stressors and physical strains (as indicated by absence, doctor visits, and physical symptoms). Contrary to the results of Brief, Burke, George, Robinson, and Webster (1988), NA did not account for much of the variance shared by stressors and affective strains (job satisfaction, anger, and feelings of stress and frustration). Reasons for the failure of this and several earlier studies to successfully replicate Brief et al.'s results are explored.}, } @article {pmid2059747, year = {1991}, author = {Dritschel, BH and Teasdale, JD}, title = {Individual differences in affect-related cognitive operations elicited by experimental stimuli.}, journal = {The British journal of clinical psychology}, volume = {30}, number = {2}, pages = {151-160}, doi = {10.1111/j.2044-8260.1991.tb00930.x}, pmid = {2059747}, issn = {0144-6657}, mesh = {Adult ; *Affect ; *Cognition ; Depressive Disorder/psychology ; Extraversion, Psychological ; Female ; Humans ; *Individuality ; Models, Psychological ; Neurotic Disorders/psychology ; *Personality ; Risk Factors ; }, abstract = {Beck's cognitive model of depression suggests the importance of cognitive distortions, such as overgeneralization and personalization, in the aetiology of depression. Larsen, Diener & Cropanzano (1987) developed a method for directly measuring the cognitive operations of overgeneralization and personalization in the reactions of normal subjects to experimentally presented visual stimuli. The present study employed this method to examine the relationship between use of these cognitive operations and the personality dimensions of affect intensity, neuroticism and extraversion. Results showed that high scorers on affect intensity exhibited more evidence of overgeneralization and personalization, replicating Larsen et al.'s (1987) findings, with a similar effect for neuroticism. The results suggest that the persistent differences in response to emotional events measured by the traits of affect intensity and neuroticism may be mediated by particular styles of cognitive processing.}, } @article {pmid2039272, year = {1991}, author = {Satin, KP and Neutra, RR and Guirguis, G and Flessel, P}, title = {Umbilical cord blood lead levels in California.}, journal = {Archives of environmental health}, volume = {46}, number = {3}, pages = {167-173}, doi = {10.1080/00039896.1991.9937445}, pmid = {2039272}, issn = {0003-9896}, mesh = {Air Pollutants/*analysis ; Birth Weight ; California/epidemiology ; Female ; Fetal Blood/*chemistry ; Gestational Age ; Health Status Indicators ; Humans ; Infant, Newborn ; Infant, Premature ; Lead/*analysis ; Lead Poisoning/*blood/epidemiology ; Male ; Maternal Age ; Risk Factors ; }, abstract = {During the fall of 1984, we conducted a survey of umbilical cord blood lead levels of 723 live births that occurred at 5 hospitals located in 5 cities in California. Historical ambient air lead levels were used as a qualitative surrogate of air and dust exposure. The area-specific cord blood means (all means approximately 5 micrograms/dl), medians, deciles, and distributions did not vary among locations. The California distributions included means that were lower than the 6.6 micrograms/dl reported in Needleman et al.'s Boston study in 1979. Indeed, the entire California distribution was shifted to the left of the Boston study distribution, even though 3% of the California cord lead levels exceeded 10 micrograms/dl--the level above which Needleman et al. have documented psychoneurological effects in children during the first few years of life. Fourteen percent of premature babies had cord blood lead levels above 10 micrograms/dl. The association between prematurity (i.e., less than 260 d gestation) and elevated (greater than 5 micrograms/dl) cord blood lead was observed in all hospitals and yielded a relative risk of 2.9 (95% CI: .9, 9.2) and a population attributable risk of 47%. Further research is needed to confirm this association and to explore the roles of endogenous and exogenous sources of lead exposure to the mothers who give birth to premature infants.}, } @article {pmid2030180, year = {1991}, author = {Beutler, LE}, title = {Have all won and must all have prizes? Revisiting Luborsky et al.'s verdict.}, journal = {Journal of consulting and clinical psychology}, volume = {59}, number = {2}, pages = {226-232}, doi = {10.1037//0022-006x.59.2.226}, pmid = {2030180}, issn = {0022-006X}, support = {39859//PHS HHS/United States ; }, mesh = {Follow-Up Studies ; Humans ; *Individuality ; *Personality Development ; Psychotherapy/*methods ; }, abstract = {Although most reviews of comparative psychotherapy literature have failed to find significant differences among treatments, it is premature to give up the search for differential effects. There are a large number of patient, therapist, and treatment variables that may mediate the effects of treatments. Given the enormity of the task of exploring potential interactions among the many patient, therapist, and psychotherapy types, a guiding model is needed by which to narrow our search for variables that mediate between treatment type and outcome. However, theoretical constructs that represent both patient and therapy variations frequently are poorly defined. Tests of treatment selection models that cut across narrow theoretical differences among psychotherapies and that operationalize definitions of patient types hold promise for revealing meaningful Patient x Therapist interaction effects in psychotherapy.}, } @article {pmid2030122, year = {1991}, author = {Watson, CG and Juba, MP and Manifold, V and Kucala, T and Anderson, PE}, title = {The PTSD interview: rationale, description, reliability, and concurrent validity of a DSM-III-based technique.}, journal = {Journal of clinical psychology}, volume = {47}, number = {2}, pages = {179-188}, doi = {10.1002/1097-4679(199103)47:2<179::aid-jclp2270470202>3.0.co;2-p}, pmid = {2030122}, issn = {0021-9762}, mesh = {Adult ; Humans ; Life Change Events ; MMPI/standards ; Male ; Psychiatric Status Rating Scales/instrumentation/*standards ; Psychometrics ; Sensitivity and Specificity ; Severity of Illness Index ; Stress Disorders, Post-Traumatic/classification/*diagnosis/psychology ; Terminology as Topic ; }, abstract = {This paper describes the PTSD Interview (PTSD-I). It was developed to meet four specifications: (a) close correspondence to DSM-III standards; (b) binary present/absent and continuous severity/frequency outputs on each symptom and the entire syndrome; (c) administrable by trained subprofessionals; and (d) substantial reliability and validity. It was written to meet the first three criteria. It demonstrated very high internal consistency (alpha = .92) and test-retest reliability (Total score r = .95; diagnostic agreement = 87%). It correlated strongly with parallel DIS criteria (Total score vs. DIS diagnosis rbis = .94, sensitivity = .89, specificity = .94, overall hit rate = .92, and kappa = .84). Earlier studies revealed correlations with a military stress scale and Keane et al.'s MMPI PTSD subscale. It is apparently the only PTSD instrument that meets all of the above criteria.}, } @article {pmid2028090, year = {1991}, author = {Sidaway, B and Moore, B and Schoenfelder-Zohdi, B}, title = {Summary and frequency of KR presentation effects on retention of a motor skill.}, journal = {Research quarterly for exercise and sport}, volume = {62}, number = {1}, pages = {27-32}, doi = {10.1080/02701367.1991.10607515}, pmid = {2028090}, issn = {0270-1367}, mesh = {Female ; Humans ; *Knowledge of Results, Psychological ; *Motor Skills ; *Retention, Psychology ; Time and Motion Studies ; }, abstract = {This experiment investigates the recent proposal of Schmidt, Young, Swinnen, and Shapiro (1989) that summary knowledge of results (KR) improves skill retention. In Schmidt et al.'s experiment, however, summary length varied concomitantly with the frequency of KR presentation. The current investigation held KR presentation frequency constant while manipulating the number of trials seen in the summary KR display. Subjects were required to perform a timing task on a linear slide. Five groups (n = 12) of subjects participated in acquisition trials then in 10-min and 2-day delayed no-KR retention tests. In 4 conditions, subjects completed each acquisition block without any KR, but following each block they received KR on either 15, 7, 3, or 1 of the 15 trials performed in that block. In the final condition subjects received immediate KR. Analysis of the absolute constant error (magnitude of CE) data for acquisition revealed all groups improved with practice and the immediate KR group performed better than all the summary groups which in turn did not differ significantly. Analysis of the magnitude of CE retention data found performance to be worse on the 2-day retention test for all groups. The effect of condition was significant. The 1/1 group had lower error scores than all other groups, which in turn were not significantly different. Analyses of variable error (VE) revealed only that VE decreased with practice. These findings suggest frequency of KR presentation may be the basis for the summary KR effect found by Schmidt et al. (1989).}, } @article {pmid2036585, year = {1991}, author = {Cordes, AK and Gow, ML and Ingham, RJ}, title = {On valid and reliable identification of normal disfluencies and stuttering disfluencies: a response to Aram, Meyers, and Ekelman (1990).}, journal = {Brain and language}, volume = {40}, number = {2}, pages = {282-6; discussion 287-92}, doi = {10.1016/0093-934x(91)90129-o}, pmid = {2036585}, issn = {0093-934X}, mesh = {Brain Damage, Chronic/diagnosis/*physiopathology ; Brain Mapping ; Child ; Dominance, Cerebral/*physiology ; Humans ; Stuttering/diagnosis/*physiopathology ; Verbal Behavior/*physiology ; }, abstract = {Aram, Meyers, and Ekelman (1990, Brain and Language, 38, 105-121) recently reported finding that children with unilateral brain lesions produced more stuttering-type nonfluencies than their neurologically normal peers. However, they did not report inter- or intrajudge agreement for the nonfluency types or for their method of measuring speech rate. The speech rates they reported were also unusually fast. We argue that these problems with Aram et al.'s study imperil both their results and their conclusions regarding developmental stuttering.}, } @article {pmid1867145, year = {1991}, author = {Gottlieb, BH}, title = {Peer telephone dyads: putting conclusions on hold.}, journal = {American journal of community psychology}, volume = {19}, number = {1}, pages = {123-132}, doi = {10.1007/BF00942260}, pmid = {1867145}, issn = {0091-0562}, mesh = {Aged/*psychology ; Female ; *Hotlines ; Humans ; Interpersonal Relations ; *Peer Group ; Poverty ; *Social Support ; }, abstract = {Commentary on Heller et al.'s (1991) peer telephone intervention for elderly women addresses three issues: (a) the sources and kinds of information needed to inform decisions about the choice of intervention; (b) the criteria used to evaluate the process and outcomes of support interventions; (c) the social psychological dynamics stimulated by the intervention protocol and by the particular form of the intervention. The latter two issues complicate interpretation of the study's findings and raise additional questions about whether and why the intervention was unsuccessful.}, } @article {pmid2047785, year = {1991}, author = {Grove, WM and Lebow, BS and Medus, C}, title = {Head size in relation to schizophrenia and schizotypy.}, journal = {Schizophrenia bulletin}, volume = {17}, number = {1}, pages = {157-161}, doi = {10.1093/schbul/17.1.157}, pmid = {2047785}, issn = {0586-7614}, mesh = {Adult ; *Cephalometry ; Female ; Humans ; Male ; Middle Aged ; Regression Analysis ; Risk Factors ; Schizophrenia/*diagnosis/genetics ; *Schizophrenic Psychology ; }, abstract = {Cranial breadth and length on DSM-III schizophrenic probands (n = 16) and their nonpsychotic siblings (n = 34) were measured using standard anthropometric calipers. Siblings were divided into those with and those without DSM-III schizotypal personality disorder based on Baron et al.'s Schedule for Schizotypal Personalities interview (1981). These siblings provide controls for prenatal and childhood nutritional status, which could affect head size, and for genetic contributors to head size. Contrary to previous reports (Andreasen et al. 1986; and Pearlson et al. 1989), in the present sample schizophrenic patients did not have smaller heads. The relationship between height and head size for schizophrenic subjects, schizotypal siblings, and nonschizotypal siblings was also examined. As in Andreasen et al. (1986), the regression slope of head size on height was lower in schizophrenic patients than in their siblings, but here this difference was not significant. The data do not support a conjectured relationship between small or dysmorphic head size and schizophrenia or schizotypy.}, } @article {pmid2017891, year = {1991}, author = {Smith, AT and Edgar, GK}, title = {The separability of temporal frequency and velocity.}, journal = {Vision research}, volume = {31}, number = {2}, pages = {321-326}, doi = {10.1016/0042-6989(91)90121-k}, pmid = {2017891}, issn = {0042-6989}, support = {//Wellcome Trust/United Kingdom ; }, mesh = {Discrimination, Psychological/physiology ; Humans ; Male ; Motion Perception/*physiology ; Pattern Recognition, Visual/physiology ; Random Allocation ; Time Factors ; }, abstract = {McKee, Silverman and Nakayama (1986; Vision Research, 26, 609-619) have shown that velocity discrimination performance is little affected by quite large random changes in the spatial frequency, and hence temporal frequency, of the grating patterns to be discriminated. We show that the converse is also true: temporal frequency discrimination can be performed despite random changes in velocity. This casts doubt on McKee et al.'s conclusion that velocity is the fundamental dimension of the temporal mechanisms mediating discrimination and that temporal frequency has to be inferred indirectly from velocity and spatial frequency. We suggest instead that both velocity and temporal frequency are represented in the visual system but that the two dimensions are only partially separable at the perceptual level.}, } @article {pmid1955208, year = {1991}, author = {Shmotkin, D}, title = {The structure of the Life Satisfaction Index A in elderly Israeli adults.}, journal = {International journal of aging & human development}, volume = {33}, number = {2}, pages = {131-150}, doi = {10.2190/ND3A-L67H-16J7-DWJT}, pmid = {1955208}, issn = {0091-4150}, mesh = {Aged/*psychology ; Aged, 80 and over ; Cultural Characteristics ; Factor Analysis, Statistical ; Female ; Humans ; Israel ; Male ; Middle Aged ; *Personal Satisfaction ; Psychological Tests/*methods ; }, abstract = {Neugaraten et al.'s Life Satisfaction Index A (LSIA) is a widely used instrument for measuring subjective well-being among elderly adults, and the generalizability of its structure in different cultural contexts should be established [1]. The present study investigated the structure of the LSIA in older Israeli adults by exploratory and confirmatory factor analyses. Exploratory factor analyses in Sample 1 (N = 267) yielded three factors of Zest, Mood Tone, and Congruence. Unlike previous studies in the United States, Zest emerged in alternate forms, labeled Zest-Via-Time and Zest-Via-Interest. Confirmatory factor analyses were conducted in Sample 1 and Sample 2 (N = 154) according to Liang's [2] model specifications, assuming a second-order factor. When previously suggested factorial compositions were tested, Liang's [2] and Hoyt and Creech's [3] three-factor models fit the data, while Adams' [4] model did not. Hoyt and Creech's [3] four-factor model provided no improvement on the two, three-factor models. When the present factorial compositions were tested, a three-factor model with Zest-Via-Interest best fit Sample 1, while an alternate three-factor model with Zest-Via-Time best fit Sample 2. A four-factor model with both forms of Zest provided no improvement on the best fitting three-factor models. The results support the generalizability of a three-factor structure with a second-order factor but suggest two different variations of Zest. Cross-cultural as well as other implications concerning subjective well-being in elderly adults are discussed.}, } @article {pmid1947875, year = {1991}, author = {Lenzenweger, MF and Dworkin, RH and Wethington, E}, title = {Examining the underlying structure of schizophrenic phenomenology: evidence for a three-process model.}, journal = {Schizophrenia bulletin}, volume = {17}, number = {3}, pages = {515-524}, doi = {10.1093/schbul/17.3.515}, pmid = {1947875}, issn = {0586-7614}, mesh = {Adult ; Diseases in Twins/psychology ; Humans ; Interpersonal Relations ; *Personality Development ; Psychiatric Status Rating Scales ; Psychometrics ; Schizophrenia/classification/*diagnosis/rehabilitation ; *Schizophrenic Psychology ; *Social Adjustment ; *Social Environment ; }, abstract = {The present report examined the latent structure of schizophrenic phenomenology. Schizophrenic patient case histories (n = 192) were rated for positive symptoms, negative symptoms, and premorbid social adjustment and the observed covariation among these clinical features was evaluated using a model-based confirmatory factor analytic approach. Our results indicated that schizophrenic phenomenology was best characterized by three distinct underlying structures. These data provide empirical support for Strauss et al.'s (1974) three-process model, which suggests that positive symptoms, negative symptoms, and disordered premorbid personal-social relationships are three distinct classes of phenomenology possibly reflective of three relatively independent pathological processes in schizophrenia. The data are also consistent with Crow's (1980, 1985, 1987) model of schizophrenic symptomatology, differentiating social impairment from both positive and negative symptoms. The heuristic implications of these data for the development of schizophrenia are discussed and the utility of a replication of the present study is noted.}, } @article {pmid1789165, year = {1991}, author = {Keith, JB and McCreary, C and Collins, K and Smith, CP and Bernstein, I}, title = {Sexual activity and contraceptive use among low-income urban black adolescent females.}, journal = {Adolescence}, volume = {26}, number = {104}, pages = {769-785}, pmid = {1789165}, issn = {0001-8449}, support = {FPR 000047/FP/OFP OPHS HHS/United States ; }, mesh = {Adolescent ; *Adolescent Behavior ; Black or African American/*psychology ; Age Factors ; Attitude ; Contraception/*statistics & numerical data ; Family ; Female ; Humans ; Models, Psychological ; Pregnancy ; Pregnancy in Adolescence/psychology ; *Sexual Behavior ; Social Class ; Surveys and Questionnaires ; }, abstract = {A modified form of Nathanson and Becker's (1983) Health Belief Model Questionnaire and other measures designed to assess cognitive processing were administered to low-income black adolescent female clients of an inner-city comprehensive health care clinic. The purpose of the study was to explore determinants of sexual activity and contraceptive use. Subjects were classified as not sexually active (n = 50), sexually active/noncontracepting (n = 20), or sexually active/contracepting (n = 72). Not sexually active subjects tended to be younger, more career motivated, to have a father at home, to be more influenced by family values, and to have more conservative attitudes regarding adolescent sexuality than did sexually active subjects. Sexually active/noncontracepting subjects tended to report fewer benefits and more barriers to the use of contraception. Level of cognitive processing did not differ among the three groups, but was at a lower-than-expected level for age. Finally, inconsistent contraceptive use was common to both sexually active groups.}, } @article {pmid2249193, year = {1990}, author = {Potish, RA and Farniok, KE and Twiggs, LB}, title = {The interplay of local and distant control in the cure of cervical cancer.}, journal = {Cancer}, volume = {66}, number = {12}, pages = {2514-2521}, doi = {10.1002/1097-0142(19901215)66:12<2514::aid-cncr2820661212>3.0.co;2-x}, pmid = {2249193}, issn = {0008-543X}, mesh = {Adult ; Aged ; Combined Modality Therapy ; Female ; Follow-Up Studies ; Humans ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Recurrence, Local ; Survival Rate ; Uterine Cervical Neoplasms/mortality/*pathology/radiotherapy/surgery ; }, abstract = {From 1978 to 1986, 183 women with cervical cancer received definitive radiation therapy after extraperitoneal surgical staging. Relapse-free rates were strong functions of pelvic lymph node metastases and cervical size. The recurrence distribution consisted of 4% isolated local, 13% isolated distant, and 17% combined local and distant failures. With the assumption of independent local and distant failure probabilities, Suit et al.'s method was extended to assess potential improvement in cure attainable with perfect local and distant control, yielding local (LSA) and distant (DSA) survival advantages of 17% and 28%. Various subsets of clinical stage, cervical size, pelvic node metastases, periaortic metastases, and peritoneal metastases had LSA from 12% to 27% and DSA from 12% to 71%. For any prognostic group, LSA never exceeded DSA, showing that effective systemic therapy would have a greater impact on improving survival than would advances in local and regional tumor control. Therapeutic implications and limitations of the extended LSA-DSA model are discussed. This form of analysis can be used to guide the intensity of local and distant treatment to maximize the cure of the patient with cancer.}, } @article {pmid2292642, year = {1990}, author = {Quinsey, VL and Laws, DR}, title = {Validity of physiological measures of pedophilic sexual arousal in a sexual offender population: a critique of Hall, Proctor, and Nelson.}, journal = {Journal of consulting and clinical psychology}, volume = {58}, number = {6}, pages = {886-891}, doi = {10.1037/0022-006x.58.6.886}, pmid = {2292642}, issn = {0022-006X}, mesh = {*Arousal ; Humans ; Male ; Pedophilia/*diagnosis/psychology ; Penile Erection ; Reproducibility of Results ; }, abstract = {It is argued that methodological problems in Hall, Proctor, and Nelson's (1988) comparison of phallometric data on child molesters and rapists include confounding of stimulus category and duration, omission of neutral stimuli and a normal control group, failure to employ relative measures of sexual preference, and failure to exclude subjects who did not respond to the sexual stimuli. Quinsey and Laws maintain that, although these methodological problems preclude accepting the conclusions drawn in Hall et al.'s article, the problems illustrate the need to develop common methodological standards for phallometric research on sexual offenders.}, } @article {pmid2287786, year = {1990}, author = {Wartenberg, D and Gallo, MA}, title = {The fallacy of ranking possible carcinogen hazards using the TD50.}, journal = {Risk analysis : an official publication of the Society for Risk Analysis}, volume = {10}, number = {4}, pages = {609-613}, doi = {10.1111/j.1539-6924.1990.tb00546.x}, pmid = {2287786}, issn = {0272-4332}, mesh = {Animals ; Carcinogens/*toxicity ; Humans ; Maximum Allowable Concentration ; Models, Biological ; Reproducibility of Results ; Risk ; }, abstract = {Ames et al. have proposed a new model for evaluating carcinogenic hazards in the environment. They advocate ranking possible carcinogens on the basis of the TD50, the estimated dose at which 50% of the test animals would get tumors, and extrapolating that ranking to all other doses. We argue that implicit in this methodology is a simplistic and inappropriate statistical model. All carcinogens are assumed to act similarly and to have dose-response curves of the same shape that differ only in the value of one parameter. We show by counterexample that the rank order of cancer potencies for two chemicals can change over a reasonable range of doses. Ames et al.'s use of these TD50 ranks to compare the hazards from low level exposures to contaminants in our food and environment is wholly inappropriate and inaccurate. Their dismissal of public health concern for environmental exposures, in general, based on these comparisons, is not supported by the data.}, } @article {pmid2287673, year = {1990}, author = {Schill, T and Wang, S}, title = {Correlates of the MMPI-2 anger content scale.}, journal = {Psychological reports}, volume = {67}, number = {3 Pt 1}, pages = {800-802}, doi = {10.2466/pr0.1990.67.3.800}, pmid = {2287673}, issn = {0033-2941}, mesh = {Adult ; *Anger ; Female ; *Hostility ; Humans ; *Internal-External Control ; *MMPI ; Male ; Psychometrics ; Violence ; }, abstract = {Scores on the MMPI-2 anger-content scale were correlated with those on Spielberger's anger expression scale, Zelin, et al.'s anger self-report scale, and the Cook and Medley hostility scale. Subjects were 32 men and 33 women in college. As expected, the anger-content scale correlated significantly with measures of anger awareness, anger expression (anger out versus anger in), and negatively with anger control. There was also a significant correlation with measures of hostility (projection of anger) for men.}, } @article {pmid2135937, year = {1990}, author = {Link, BG and Mesagno, FP and Lubner, ME and Dohrenwend, BP}, title = {Problems in measuring role strains and social functioning in relation to psychological symptoms.}, journal = {Journal of health and social behavior}, volume = {31}, number = {4}, pages = {354-369}, pmid = {2135937}, issn = {0022-1465}, support = {MH13403/MH/NIMH NIH HHS/United States ; MH36208/MH/NIMH NIH HHS/United States ; }, mesh = {Educational Status ; Follow-Up Studies ; Humans ; Life Change Events ; Mental Disorders/diagnosis/epidemiology/*psychology ; New York City/epidemiology ; Racial Groups ; *Role ; Social Environment ; Stress, Psychological/etiology/psychology ; United States ; }, abstract = {The problems that people experience in social roles can be regarded as either causes or consequences of psychological symptoms. To reflect one of these possibilities, Pearlin et al. (1981) developed measures of "role strains" which are considered sources of psychopathology. To reflect the other position, Dohrenwend et al. (1981) constructed measures of "role functioning" which are seen as consequences of psychopathology. We show that the measures developed by these two teams of investigators are similar in content and show substantial empirical overlap despite the different meanings attributed to them. In an effort to understand whether these highly correlated measures assess, "role strain" or "role functioning," we conduct an exploratory analysis of marital and housework role problems, using a small panel sample of New York City residents. Specifically, we use instrumental variables to identify reciprocal effects between psychological distress and each role area. We find that the relationship between housework role problems and distress is more consistent with Pearlin et al.'s interpretation, whereas the relationship between marital problems and distress is more consistent with that of Dohrenwend et al. Investigators interested in measuring either role strain or role functioning must bear in mind the strong possibility of contamination from the other construct.}, } @article {pmid2395463, year = {1990}, author = {Stein, PE and Leslie, AG and Finch, JT and Turnell, WG and McLaughlin, PJ and Carrell, RW}, title = {Crystal structure of ovalbumin as a model for the reactive centre of serpins.}, journal = {Nature}, volume = {347}, number = {6288}, pages = {99-102}, doi = {10.1038/347099a0}, pmid = {2395463}, issn = {0028-0836}, support = {//Wellcome Trust/United Kingdom ; }, mesh = {Amino Acid Sequence ; Binding Sites ; Crystallization ; Models, Molecular ; Molecular Sequence Data ; Molecular Structure ; *Ovalbumin ; Protein Conformation ; Sequence Homology, Nucleic Acid ; *Serpins ; alpha 1-Antitrypsin ; }, abstract = {The serpins are a widely distributed family of proteins with diverse functions; they include the key serine protease inhibitors of human plasma as well as noninhibitory homologues such as hormone-binding globulins, angiotensinogen and egg-white ovalbumin. Sequence alignment based on the crystal structure. On the cleaved form of the archetypal serpin, alpha 1-antitrypsin, indicates that the serpins share a common highly ordered structure. On cleavage of the reactive centre peptide bond, they characteristically undergo a remarkable conformational change, the newly generated C terminus moving some 70 A to the opposite pole of the molecule. The structure of this post-cleavage form is known, but the conformation of the intact serpins and in particular that of their reactive centre is not. Wright et al.'s structure of plakalbumin (ovalbumin cleaved by subtilisin) has provided evidence for the conformational change that results from cleavage. We have now determined the structure of native ovalbumin to 1.95 A resolution and have found that the intact peptide loop forming the analogue to the reactive centre of the inhibitory serpins takes the unexpected form of a protruding, isolated helix. This model of the intact structures of the serpins suggests how they may interact with their target proteases.}, } @article {pmid2381322, year = {1990}, author = {Greenwald, AG and Klinger, MR}, title = {Visual masking and unconscious processing: differences between backward and simultaneous masking?.}, journal = {Memory & cognition}, volume = {18}, number = {4}, pages = {430-435}, pmid = {2381322}, issn = {0090-502X}, support = {MH-41328/MH/NIMH NIH HHS/United States ; RR-07096/RR/NCRR NIH HHS/United States ; }, mesh = {Adult ; *Attention ; *Awareness ; *Cognition ; Discrimination Learning ; Female ; *Form Perception ; Humans ; Male ; *Pattern Recognition, Visual ; *Perceptual Masking ; *Semantics ; }, abstract = {Visual masking procedures are considered to have great potential for studying information processing that occurs outside of consciousness. Unfortunately, effects that indicate processing of masked word stimuli have been both difficult to obtain and, once obtained, difficult to replicate. The present seven experiments failed to obtain an effect of lexicality (word vs. nonword targets) on detection that was recently reported by Doyle and Leach (1988). Whereas Doyle and Leach had used backward binocular masking, most of the present experiments used simultaneous dichoptic masking. Doyle (1990) recently suggested that the effect of lexicality on detection (coupled with an effect of knowledge of results, which was also not obtained in the present research) could explain why Greenwald, Klinger, and Liu (1989) found no evidence for detectability of masked words that were nevertheless analyzed semantically. The differences of the present findings from those of Doyle and Leach (1988) not only confirm the uncertainty of generalizing across masking procedures, but also indicate that Greenwald et al.'s "detectionless processing" interpretation remains viable.}, } @article {pmid2212055, year = {1990}, author = {Turner, JA and Mayr, S}, title = {Interpersonal types among alcohol abusers: a comparison with drug abusers.}, journal = {Journal of clinical psychology}, volume = {46}, number = {4}, pages = {500-506}, doi = {10.1002/1097-4679(199007)46:4<500::aid-jclp2270460419>3.0.co;2-g}, pmid = {2212055}, issn = {0021-9762}, mesh = {Adult ; Alcoholism/*psychology/rehabilitation ; Humans ; *Interpersonal Relations ; Male ; *Personality Inventory ; Psychometrics ; Social Adjustment ; Social Environment ; Social Support ; Substance-Related Disorders/*psychology/rehabilitation ; Veterans/*psychology ; }, abstract = {Interpersonal types among alcohol abusers were examined with Calsyn, Roszell, and Anderson's (1988) nine-type system for classifying FIRO-B profiles. The frequencies of the nine FIRO-B types among a sample of 135 male veteran alcohol abusers were compared with Calsyn et al.'s (1988) previously published data for a sample of male veteran drug abusers, a normative veteran sample, and a general population sample. The alcohol abusers, like Calsyn et al.'s sample of drug abusers, were more likely to be categorized as "loners," "rebels," and "pessimists" than was the general population sample. While exhibiting preferences for interpersonal types that emphasized social withdrawal, avoidance of responsibility, and mistrust of others, both the alcohol abusers and the drug abusers were heterogeneous groups whose members demonstrated a variety of interpersonal types.}, } @article {pmid2364736, year = {1990}, author = {Kemler Nelson, DG}, title = {When experimental findings conflict with everyday observations: reflections on children's category learning.}, journal = {Child development}, volume = {61}, number = {3}, pages = {606-610}, pmid = {2364736}, issn = {0009-3920}, mesh = {Attention ; Child ; *Child Development ; *Concept Formation ; *Discrimination Learning ; Humans ; *Social Environment ; }, abstract = {Attempts to reconcile the ease with which young children naturally learn everyday categories with their frequent difficulty in acquiring artificial categories in the laboratory have taken different forms. Kemler Nelson suggested that one reason for the discrepancy may be that many everyday object categories have a family-resemblance structure that can be learned by means of a holistic mode of processing. While Ward et al. have recently questioned this account of why children learn family-resemblance categories easily, conclusions based on their laboratory data fail to provide a good explanation of the real-world case. Accordingly, it is suggested that the laboratory family-resemblance task used by these previous investigators may be unrepresentative and may fail to mimic crucial aspects of the everyday category-learning context. It is also suggested that aspects of Ward et al.'s methodology may lead them to underestimate holistic (or nonselective) processing.}, } @article {pmid2214320, year = {1990}, author = {Iwasaki, S and Ideura, T and Yoshimura, A and Chimata, M and Kawamura, M and Sudo, M and Koshikawa, S}, title = {[High deposition rate of aluminum in tissues in diabetic hemodialysis patients].}, journal = {Nihon Jinzo Gakkai shi}, volume = {32}, number = {6}, pages = {723-728}, pmid = {2214320}, issn = {0385-2385}, mesh = {Adult ; Aged ; Aluminum/*pharmacokinetics ; Deferoxamine ; Diabetic Nephropathies/*metabolism/therapy ; Female ; Glomerulonephritis/metabolism/therapy ; Humans ; Male ; Middle Aged ; *Renal Dialysis ; Tissue Distribution ; }, abstract = {Aluminum (Al) accumulation in bone is a serious problem in patients on hemodialysis. We studied deferoxamine infusion test (DFO test) in 14 diabetic patients on hemodialysis (HDDM) and 23 hemodialysis patients originated from glomerulo nephritis (HDCGN) to determine whether Al accumulation is different between the two groups or not. There was no difference in hemodialysis duration and total oral intake of Al containing drugs between two groups. Serum C-terminal parathyroid hormone (C-PTH) in HDDM was lower than that in HDCGN group (1.82 +/- 1.30 vs. 3.80 +/- 1.82 ng/ml; P less than 0.01). However serum Al (s-Al) levels were comparable (61.9 +/- 53.0 vs, 45.0 +/- 32.3 micrograms/l). A significant correlation was observed between duration of dialysis period and s-Al in HDDM (r = 0.806, p less than 0.01), but in HDCGN, the relation was not significant. The patients in HDDM whose cumulative aluminum intake was less than 2.0 kg showed the higher serum A1 concentrations before DFO and greater increases in s-Al after DFO test, as compared with those in HDCGN with matched aluminum intake (93.8 +/- 67.6 vs. 35.9 +/- 23.6 micrograms/l; p less than 0.001 and 141.2 +/- 81.8 vs. 70.3 +/- 41.1 micrograms/l; p = 0.035). These results indicate that in uremic diabetic patients with lower intake of Al containing drugs, an early accumulation of Al in the whole body occurs possibly because of the enhanced absorption rate of Al at an intestine and/or the low PTH level.}, } @article {pmid2141355, year = {1990}, author = {Balota, DA and Chumbley, JI}, title = {Where are the effects of frequency in visual word recognition tasks? Right where we said they were! Comment on Monsell, Doyle, and Haggard (1989).}, journal = {Journal of experimental psychology. General}, volume = {119}, number = {2}, pages = {231-237}, doi = {10.1037//0096-3445.119.2.231}, pmid = {2141355}, issn = {0096-3445}, mesh = {*Attention ; *Form Perception ; Humans ; *Pattern Recognition, Visual ; Problem Solving ; Reaction Time ; *Reading ; *Semantics ; Verbal Learning ; }, abstract = {Balota and Chumbley's studies led them to conclude that category verification, lexical decision, and pronunciation tasks involve combinations of processes that cause them to produce differing estimates of the relation between word frequency and ease of lexical identification. Monsell, Doyle, and Haggard challenged Balota and Chumbley's empirical evidence and conclusions, provided empirical evidence to support their challenge, and presented an alternative theoretical position. We show that Monsell et al.'s experiments, analyses, and theoretical perspective do not result in conclusions about the role of word frequency in category verification, lexical decision, and pronunciation that differ from those of Balota and Chumbley.}, } @article {pmid2354279, year = {1990}, author = {McCown, W}, title = {The effect of impulsivity and empathy on abstinence of poly-substance abusers: a prospective study.}, journal = {British journal of addiction}, volume = {85}, number = {5}, pages = {635-637}, doi = {10.1111/j.1360-0443.1990.tb03524.x}, pmid = {2354279}, issn = {0952-0481}, mesh = {Alcoholism/psychology/*rehabilitation ; *Empathy ; Humans ; Impulsive Behavior/*psychology ; Prognosis ; *Self-Help Groups ; Substance-Related Disorders/psychology/*rehabilitation ; }, abstract = {The relation between impulsivity, empathy, and abstinence of poly-substance abusers in self-help groups is investigated prospectively. Utilizing S. B. G Eysenck et al.s' Impulsivity Questionnaire (17), new self-help 'club' members were assessed for traits of empathy and impulsivity. Abstinence was assessed one year later. Impulsivity correlated negatively with abstinence and positively with numbers of 'slips'. Contrary to previous research, empathy failed to correlate with either variable. Possible interpretations and future research directions are discussed.}, } @article {pmid2236437, year = {1990}, author = {Somsen, RJ and Jennings, JR}, title = {What is "the vagal effect"? A rejoinder to Velden et al.'s interpretation of the cardiac cycle time effect.}, journal = {Psychophysiology}, volume = {27}, number = {3}, pages = {351-357}, doi = {10.1111/j.1469-8986.1990.tb00395.x}, pmid = {2236437}, issn = {0048-5772}, mesh = {Arousal/*physiology ; *Electrocardiography ; Heart/*innervation ; Heart Rate/*physiology ; Humans ; Psychophysiology ; Vagus Nerve/*physiology ; }, } @article {pmid1694840, year = {1990}, author = {Yanagisawa, A and Yotsumoto, K and Kitagawa, T and Sugano, H and Kato, Y}, title = {Red and blue distinctive mucin-histochemical types of Japanese colorectal mucosa.}, journal = {Japanese journal of cancer research : Gann}, volume = {81}, number = {4}, pages = {372-375}, pmid = {1694840}, issn = {0910-5050}, mesh = {Adolescent ; Adult ; Aged ; Aging/metabolism ; Child ; Child, Preschool ; Colon/*metabolism ; Female ; Histocytochemistry/*methods ; Humans ; Infant ; Infant, Newborn ; Intestinal Mucosa/*metabolism ; Male ; Middle Aged ; Mucins/*metabolism ; Rectum/*metabolism ; Staining and Labeling ; }, abstract = {Mucin-histochemical characteristics of normal human colorectal mucosa were investigated utilizing Culling et al.'s staining method which distinguishes the mode of C8-O-acylation of sialomucins. Normal mucosae of cecum, ascending, transverse and descending colon and rectum were obtained from autopsy and biopsy material. Japanese colorectal mucosa stained either entirely red or entirely blue, in contrast to previous reports dealing with Caucasians where all the normal mucosa reportedly stained red. The ratio of red to blue colon cases varied to some extent with age, i.e. it was found to be 1:1 in children aged 0 to 4, 2:1 in the 5-20 age group, and 4:1 in people older than 21 years, suggesting a tendency of shift from blue to red during early life in Japan. Each individual Japanese adult colorectal mucosa may thus be classified into either red or blue type mucin-histochemically.}, } @article {pmid2137864, year = {1990}, author = {Garrod, S and O'Brien, EJ and Morris, RK and Rayner, K}, title = {Elaborative inferencing as an active or passive process.}, journal = {Journal of experimental psychology. Learning, memory, and cognition}, volume = {16}, number = {2}, pages = {250-257}, doi = {10.1037//0278-7393.16.2.250}, pmid = {2137864}, issn = {0278-7393}, support = {HD17246/HD/NICHD NIH HHS/United States ; }, mesh = {*Attention ; *Cognition ; Cues ; Fixation, Ocular ; Humans ; Memory ; Models, Psychological ; *Reading ; Time Factors ; }, abstract = {O'Brien, Shank, Myers, and Rayner (1988) reported that readers generated elaborative inferences only when a text contained characteristics that virtually eliminated the possibility of an inference being disconfirmed. We reanalyzed the data of O'Brien et al. (1988) and also conducted an experiment in which we varied (a) whether or not there was an anaphoric relation between a target word and its prior mention in the text and (b) the explicitness of the prior mention. Two refinements to O'Brien et al.'s conclusions are offered. First, the two text characteristics they manipulated (a strong biasing context or a demand sentence) may have produced different types of elaborative inferencing. We argue that a biasing context results in a passive form of elaborative inferencing, involving setting up a context of interpretation, whereas the presence of a demand sentence invites the reader to actively predict a subsequent expression. Second, clear evidence for either type of inference will be apparent only with truly anaphoric materials.}, } @article {pmid2295869, year = {1990}, author = {Batchelor, ES and Gray, JW and Dean, RS}, title = {Empirical testing of a cognitive model to account for neuropsychological functioning underlying arithmetic problem solving.}, journal = {Journal of learning disabilities}, volume = {23}, number = {1}, pages = {38-42}, doi = {10.1177/002221949002300110}, pmid = {2295869}, issn = {0022-2194}, support = {IR15HD23154/HD/NICHD NIH HHS/United States ; }, mesh = {Adolescent ; Child ; *Cognition ; Female ; Humans ; Learning Disabilities/*psychology ; Male ; *Mathematics ; *Models, Psychological ; *Neuropsychological Tests ; Problem Solving ; }, abstract = {The efficacy of a cognitive-based arithmetic problem-solving model (Dinnel, Glover, & Halpain, in press; Dinnel, Glover, & Ronning, 1984) was tested using 989 students with learning disabilities. Comprehensive neuropsychological test battery information was used to predict composite arithmetic test performance as a means of examining the utility of this model. Results of this study offer support for Dinnel et al.'s (Dinnel, Glover, & Halpain, in press; Dinnel, Glover, & Ronning, 1984) model in accounting for arithmetic performance under continuous visual stimulus conditions. However, these data indicate a more complex neuropsychological underpinning to arithmetic performance in both visual and aural stimulus conditions. The neuropsychological aspects of arithmetic problem solving were discussed in relationship to this cognitive-based model.}, } @article {pmid2149941, year = {1990}, author = {Serra, A and Bova, R}, title = {Acrocentric chromosome double NOR is not a risk factor for Down syndrome.}, journal = {American journal of medical genetics. Supplement}, volume = {7}, number = {}, pages = {169-174}, doi = {10.1002/ajmg.1320370734}, pmid = {2149941}, issn = {1040-3787}, mesh = {Case-Control Studies ; Cells, Cultured ; Centromere/ultrastructure ; Chromosomes, Human/*ultrastructure ; Down Syndrome/*genetics ; Female ; Humans ; Karyotyping ; Male ; *Nucleolus Organizer Region ; Polymorphism, Genetic ; Risk Factors ; }, abstract = {Jackson-Cook et al. (American Journal of Human Genetics 37:1049-1061, 1985) predicted a high risk of Down syndrome (DS) children for parents carrying a double NOR on acrocentric chromosomes. Hassold et al. (Human Genetics 76:381-384, 1987) could not confirm Jackson-Cook et al.'s findings, thus casting doubts on their conclusions. We studied the NORs of 1) 60 parents of 30 unselected DS subjects; 2) 30 unselected healthy subjects without trisomic offspring, who asked for chromosome analysis; and 3) 100 slides randomly chosen among 1,000 prepared by routine standard techniques and belonging to subjects who were chromosomally normal. By applying rigorously established techniques and scoring criteria we found 4 subjects (6.7%) with strictly defined double NORs (dNORs) in the DS parents sample, 2 subjects (6.7%) in the first control sample, and 3 (3%) in the second control sample. No significant difference among the observed frequencies of dNORs in the 3 samples could be demonstrated. Therefore, our data do not support Jackson-Cook et al.'s statements on the association of dNOR carrier status with DS offspring and on a highly increased risk of meiotic nondisjunction of chromosome 21 for a dNOR carrier parent. A tentative interpretation of the apparently contrasting cytogenetic findings would indicate that sampling and assignment biases are the main causes of this discrepancy.}, } @article {pmid2138268, year = {1990}, author = {Mühlenberg, W}, title = {[High aluminum concentrations in well water of southern Lower Saxony sandy soil areas caused by acid precipitation--evaluation from the public health and ecologic viewpoint].}, journal = {Das Offentliche Gesundheitswesen}, volume = {52}, number = {1}, pages = {1-8}, pmid = {2138268}, issn = {0029-8573}, mesh = {Acid Rain/*adverse effects ; Germany, West ; Humans ; Hydrogen-Ion Concentration ; Water Pollution, Chemical/*analysis ; Water Supply/*analysis ; }, abstract = {Decades of acid precipitation have caused soil acidification in regions with low neutralizing capacity of industrial countries, thus mobilizing aluminium from clay minerals into soil solution and ground water. In the southern sandy heath-land of Lower Saxony all the wells with pH values lower than 4.5 showed aluminium contents higher than 2.0 mg/l. 66.7% of the specimens within the pH-range 4.5 to 5.0 and 20% of the specimens within the pH-range 5.0 to 5.5 had aluminium levels of more than 0.2 mg/l, that is the maximum permissible limit value of the drinking water regulation. High contents of aluminium in drinking water are objectionable from the hygienic point of view, as they may cause intoxications in infants and patients with impaired renal function. In addition to this, the involvement of aluminium in the pathogenesis of severe degenerative disorders of the central nervous system cannot be excluded, such as Alzheimers disease, amyotrophic lateral sclerosis and Parkinsons dementia.}, } @article {pmid2639591, year = {1989}, author = {Kita, T and Furuya, Y}, title = {[Mechanisms of the pulmonary congestion in ligature strangulation (VIII)].}, journal = {Igaku kenkyu. Acta medica}, volume = {59}, number = {3}, pages = {83-89}, pmid = {2639591}, issn = {0076-597X}, mesh = {Airway Obstruction/*complications ; Animals ; Epinephrine/metabolism ; Guinea Pigs ; Histamine/metabolism ; Kidney/blood supply/metabolism ; Lung/metabolism ; Male ; Norepinephrine/metabolism ; Pulmonary Edema/*etiology/physiopathology ; Spleen/blood supply/metabolism ; }, abstract = {The authors observed the localization of adrenaline, noradrenaline and histamine in the walls of splenic and renal blood vessels of ligature strangulated guinea-pigs by autoradiography and immunocytochemistry, and measured the 3H-adrenaline and 3H-noradrenaline contents of the spleen et al.'s tissues of the guinea-pigs sacrificed by ligature strangulation. In both the experimental and control groups, some silver grains were observed in the endothelial cells of splenic central arteries, splenic trabecular veins, splenic venous sinuses and renal interlobular arteries after 3H-adrenaline administrations. In the ligature strangulation, the reactions of histamine exclusively demonstrated in the Weibel-Palade bodies of the splenic central arterial endothelial cells. By radioassay, the 3H-adrenaline contents of splenic and renal tissues were more than the control groups. From the above-mentioned facts, adrenaline-induced constrictions of splenic central arteries, splenic trabecular veins and splenic venous sinuses were recognized.}, } @article {pmid2530306, year = {1989}, author = {Stadler, MA}, title = {On learning complex procedural knowledge.}, journal = {Journal of experimental psychology. Learning, memory, and cognition}, volume = {15}, number = {6}, pages = {1061-1069}, doi = {10.1037//0278-7393.15.6.1061}, pmid = {2530306}, issn = {0278-7393}, support = {R01HD15054/HD/NICHD NIH HHS/United States ; }, mesh = {Adult ; Attention ; Awareness ; *Concept Formation ; Humans ; Orientation ; Pattern Recognition, Visual ; Problem Solving ; *Psychomotor Performance ; *Serial Learning ; Transfer, Psychology ; }, abstract = {Lewicki, Czyzewska, and Hoffman (1987) demonstrated learning without awareness in a visual search task. Rules determined target location on every seventh trial on the basis of target locations in the preceding six trials. Learning was demonstrated by negative transfer effects when the rules were changed. When questioned afterwards, the subjects could not describe the rules and denied awareness of them. This experiment was designed to replicate that of Lewicki et al. and to test several hypotheses about this apparent learning without awareness. Transfer conditions were included to determine whether rule learning was primarily perceptual or motor. The present assessment of awareness was based on an objective definition of awareness, rather than a subjective definition as in Lewicki et al.'s study. Their effect was replicated, and the transfer conditions revealed that learning relied on perceptual aspects of the task. The objective measure of awareness provided further evidence that subjects were unaware of the rules.}, } @article {pmid2519560, year = {1989}, author = {Jackson, JD and Ekelund, RB}, title = {The influence of advertising on tobacco consumption: some problems with Chetwynd et al.'s analysis.}, journal = {British journal of addiction}, volume = {84}, number = {11}, pages = {1247-50; discussion 1251-4}, doi = {10.1111/j.1360-0443.1989.tb00719.x}, pmid = {2519560}, issn = {0952-0481}, mesh = {Advertising/*trends ; Cross-Sectional Studies ; Humans ; Incidence ; New Zealand/epidemiology ; Smoking/*epidemiology ; Smoking Prevention ; }, abstract = {In a recent study of the relationship between cigarette advertising and the aggregate consumption of cigarettes in New Zealand between 1973 and 1985, Chetwynd et al. (1988) argue that quarterly data suggest that advertising affects overall consumption of cigarettes with an elasticity of +0.07. In addition, they argue that advertising has a 'carry over' effect of about four quarters on current consumption. These results are potentially important for two reasons. Although the evidence is mixed, the conventional view is that cigarette advertising affects brand choice among smokers but not aggregate demand for cigarettes. Chetwynd et al.'s results, (hereafter, Chetwynd) contradict this traditional view. Secondly, if advertising does increase the aggregate demand for cigarettes, then a public policy banning cigarette advertising might reduce aggregate demand for cigarettes. Unfortunately, the Chetwynd, study is sufficiently flawed with conceptual and econometric problems that their inference that advertising increases cigarette demand is questionable. Certainly cigarette advertising may increase or decrease cigarette consumption. The point we wish to make is that, any inference one way or the other based on the results of Chetwynd, cannot be viewed as well-grounded in either scientific methodology or statistical principles.}, } @article {pmid2808734, year = {1989}, author = {Hryckowian, MJ and Gynther, MD}, title = {MMPI item subtlety: familiar vs unfamiliar constructs.}, journal = {Journal of clinical psychology}, volume = {45}, number = {5}, pages = {778-781}, doi = {10.1002/1097-4679(198909)45:5<778::aid-jclp2270450513>3.0.co;2-q}, pmid = {2808734}, issn = {0021-9762}, mesh = {Adult ; Female ; Humans ; Hysteria/diagnosis/*psychology ; *MMPI ; Male ; Paranoid Disorders/diagnosis/*psychology ; Psychometrics ; *Set, Psychology ; }, abstract = {This research was designed to clarify several issues surrounding the assessment of MMPI item subtlety. Experiment 1 asked 30 college undergraduates to define hysteria and paranoia. Results showed that 17% of the descriptions given for hysteria agreed with professional definitions, while 58% of the descriptions given for paranoia were accurate. Experiment 2 had 60 other college students rate Hy and Pa items on a subtle-obvious dimension with half the subjects receiving short definitions of the construct and half long definitions. Results showed that the additional descriptors had little effect on the classification of items as subtle, neutral or obvious regardless of scale. Correlation between these ratings derived from the scale-specific format and those obtained from a general psychopathology point of view were in the .70's for both Hy and Pa. The less familiar Hy items were significantly differentiated from Christian et al.'s (1978) ratings while the more familiar Pa items were not. How subtlety should be defined depends on the questions being asked.}, } @article {pmid2760179, year = {1989}, author = {Salmon, DP and Granholm, E and McCullough, D and Butters, N and Grant, I}, title = {Recognition memory span in mildly and moderately demented patients with Alzheimer's disease.}, journal = {Journal of clinical and experimental neuropsychology}, volume = {11}, number = {4}, pages = {429-443}, doi = {10.1080/01688638908400904}, pmid = {2760179}, issn = {1380-3395}, support = {AG-05131/AG/NIA NIH HHS/United States ; }, mesh = {Aged ; Alzheimer Disease/diagnosis/*psychology ; Attention ; Disability Evaluation ; Female ; *Form Perception ; Humans ; Male ; *Memory ; Memory, Short-Term ; *Mental Recall ; Mental Status Schedule ; Neuropsychological Tests ; Orientation ; *Pattern Recognition, Visual ; Psychomotor Performance ; *Retention, Psychology ; Verbal Learning ; }, abstract = {An abbreviated form of Moss et al.'s (1986) Recognition Span Test (RST) was administered to patients with mild or moderate dementia of the Alzheimer type (DAT) and to intact control (NC) subjects. Memory spans for verbal (i.e., words), spatial and configurational (i.e., faces) information were assessed. Delayed recall (15 s and 2 min) of the words used on the verbal recognition span was also determined. The results showed that both DAT patient groups were impaired on the three recognition tasks and that the spatial and verbal forms differentiated the mildly from the moderately demented patients. The mean overall recognition span scores (spatial + verbal + facial) differentiated between DAT patients and intact controls, with 37 of the 39 patients falling beyond the 95% confidence limits derived from the control subjects' scores. On verbal recall, both the mildly and moderately demented patients were severely impaired and evidenced a very rapid rate of forgetting between the 15-s and 2-min recall attempts. These findings suggest that the RST is not only highly sensitive to memory disorders in the early stages of DAT but also effective in discriminating among various stages of this disorder.}, } @article {pmid2586854, year = {1989}, author = {}, title = {Urbanization and breastfeeding in the Philippines.}, journal = {Nutrition reviews}, volume = {47}, number = {8}, pages = {254-255}, doi = {10.1111/j.1753-4887.1989.tb02854.x}, pmid = {2586854}, issn = {0029-6643}, mesh = {Anthropology, Cultural ; *Breast Feeding ; Cultural Characteristics ; Educational Status ; Female ; Humans ; Philippines ; Socioeconomic Factors ; Urban Population ; *Urbanization ; }, abstract = {Differences in extent and duration of breastfeeding between rural and urban areas in the Phillippines increased between 1973 and 1983.}, } @article {pmid2629476, year = {1989}, author = {Kita, T and Furuya, Y}, title = {[Mechanisms of the pulmonary congestion in ligature strangulation (V)].}, journal = {Igaku kenkyu. Acta medica}, volume = {59}, number = {2}, pages = {47-51}, pmid = {2629476}, issn = {0076-597X}, mesh = {Animals ; Asphyxia/metabolism/*physiopathology ; Extravascular Lung Water/metabolism ; Guinea Pigs ; Hematocrit ; Iron/metabolism ; Ligation ; Lung/*blood supply/metabolism ; Male ; Neck ; Viscera/metabolism ; }, abstract = {The authors measured the iron contents and 3H-water contents of the lung et al.'s tissues of the guinea-pigs sacrificed by ligature strangulation. Congestion of the heart, lung, liver and kidney and anemia of the spleen were clearly recognized. And, the increase of hematocrit value of the heart blood was observed.}, } @article {pmid2670008, year = {1989}, author = {Rodde, J}, title = {[Semiquantitative in vitro study of the etching of human enamel: scanning electron microscopy observations].}, journal = {Bulletin du Groupement international pour la recherche scientifique en stomatologie & odontologie}, volume = {32}, number = {2}, pages = {87-98}, pmid = {2670008}, issn = {0250-4693}, mesh = {*Acid Etching, Dental/methods ; *Dental Bonding/methods ; Dental Enamel/*drug effects/ultrastructure ; Dose-Response Relationship, Drug ; Evaluation Studies as Topic ; Humans ; Microscopy, Electron, Scanning ; Surface Properties ; Time Factors ; }, abstract = {The efficiency of etching using lactic, citric, hydrochloric and phosphoric acids has been studied with the scanning electron microscope on 557 human enamel surfaces. A semiquantitative assessment has been performed with reference to Silverstone et al.'s classification (1975) as regards the demineralization stages of enamel prisms and to Sheykholeslam and Buonocuore's 6 points scale as regards the etching degrees. Lactic and citric acids proved ineffective. Hydrochloric and phosphoric acids were efficient between 20 and 50% concentrations. A 1 minute etching seems optimal. A long-continued etching induces crackling of the surface enamel layer into patches which do not stick properly to the underlying enamel. Only the removal of the hypermineralized surface layer (using a diamond wheel) allows to obtain microporosities evenly distributed all over the sample surface. A mechanical treatment of enamel surfaces prior to etching is necessary especially when temporary teeth or "mature" (between 5 and 50) or "aged" (over 50) teeth are concerned.}, } @article {pmid2720191, year = {1989}, author = {McCown, W}, title = {The relationship between impulsivity, empathy and involvement in twelve step self-help substance abuse treatment groups.}, journal = {British journal of addiction}, volume = {84}, number = {4}, pages = {391-393}, doi = {10.1111/j.1360-0443.1989.tb00582.x}, pmid = {2720191}, issn = {0952-0481}, mesh = {*Empathy ; Humans ; Impulsive Behavior/*psychology ; *Patient Compliance ; Prognosis ; *Self-Help Groups ; Substance-Related Disorders/psychology/*rehabilitation ; }, abstract = {The relationship between impulsivity, empathy, substance-free lifestyle and participation in Twelve Step self-help groups is investigated. Utilizing S. B. G. Eysenck et al.s' Impulsivity Questionnaire (1-7) members of three self-help 'clubs' were assessed for traits of empathy and impulsiveness. Impulsivity correlated positively with total number of substance abuse 'slips', and negatively with total months of substance abstinence. Empathy was correlated positively with length of abstinence and hours spent in Twelve Step self-help activities per week. Possible interpretations and application of these findings to clinical recommendations are discussed.}, } @article {pmid2712688, year = {1989}, author = {Jefferson, TW and Glaros, A and Spevack, M and Boaz, TL and Murray, FT}, title = {An evaluation of the Minnesota Multiphasic Personality Inventory as a discriminator of primary organic and primary psychogenic impotence in diabetic males.}, journal = {Archives of sexual behavior}, volume = {18}, number = {2}, pages = {117-126}, pmid = {2712688}, issn = {0004-0002}, support = {DK01331/DK/NIDDK NIH HHS/United States ; DK29951/DK/NIDDK NIH HHS/United States ; RR-02/RR/NCRR NIH HHS/United States ; }, mesh = {Adult ; Aged ; *Diabetes Complications ; Diabetes Mellitus/psychology ; Diagnosis, Differential ; Erectile Dysfunction/classification/*diagnosis/etiology ; Humans ; *MMPI ; Male ; Middle Aged ; Penile Erection ; Psychophysiologic Disorders/*diagnosis ; }, abstract = {The ability of the MMPI to discriminate between primary psychogenic impotence and primary organic impotence in males with diabetes mellitus was assessed. In order to provide the MMPI with the optimal situation to discriminate between the two groups, we attempted to form a homogeneous sample in terms of physical conditions. Thirty impotent diabetic males were classified as primary organic or primary psychogenic based on nocturnal penile tumescence data. Beutler et al.'s MMPI decision rules yielded a 63% misclassification of the two groups. Possible explanations for the lack of discriminative power of the MMPI with this sample of diabetic males were discussed in relation to previous findings. The power of nocturnal penile tumescence to classify men as having primary organic or primary psychogenic impotence was examined with reference to other vascular and endocrine variables.}, } @article {pmid2923707, year = {1989}, author = {Heinrichs, RW}, title = {Attempted clinical application of a technique for promoting robust free recall to a case of alcoholic Korsakoff's syndrome.}, journal = {Brain and cognition}, volume = {9}, number = {2}, pages = {151-157}, doi = {10.1016/0278-2626(89)90026-2}, pmid = {2923707}, issn = {0278-2626}, mesh = {Alcohol Amnestic Disorder/psychology/*rehabilitation ; *Attention ; Cues ; Humans ; Male ; *Memory ; Memory, Short-Term ; *Mental Recall ; Middle Aged ; Neuropsychological Tests ; *Verbal Learning ; }, abstract = {A case study is reported which attempted to teach personal orienting information (i.e., recent history) to an amnesic male patient. The structured cuing methods reported by Kovner, Mattis, and Pass (1985, Journal of Clinical and Experimental Neuropsychology, 7, 395-411) were adopted. This involves structured presentation and cuing of target words embedded in a narrative. Some patients eventually are able to freely recall large amounts of material presented in this way. In the present case, the patient received 30 training sessions over 8 weeks. The material to be remembered was 10 target words pertaining to recent personal history. These words were embedded in accompanying storyline. The patient's immediate recall at the end of each session improved to some extent over the training period. However, delayed recall for the material remained nil throughout. Twelve months after the last training session the patient showed some "implicit" retention of the material. The findings are contrasted with Kovner et al.'s dramatic results and discussed.}, } @article {pmid2784036, year = {1989}, author = {Walker, E and Katon, W and Jones, LM and Russo, J}, title = {Relationship between endometriosis and affective disorder.}, journal = {The American journal of psychiatry}, volume = {146}, number = {3}, pages = {380-381}, doi = {10.1176/ajp.146.3.380}, pmid = {2784036}, issn = {0002-953X}, mesh = {Adult ; Cross-Sectional Studies ; Depressive Disorder/*complications/epidemiology/genetics ; Endometriosis/*complications ; Humans ; Male ; Psychiatric Status Rating Scales ; }, abstract = {Comparing 14 women with and 55 women without endometriosis, the authors found no significant differences in the prevalence of affective disorder. They discuss the discrepancy between their finding and Lewis et al.'s finding of an association between affective disorder and endometriosis.}, } @article {pmid2775142, year = {1989}, author = {Donnell, CD and McNally, RJ}, title = {Anxiety sensitivity and history of panic as predictors of response to hyperventilation.}, journal = {Behaviour research and therapy}, volume = {27}, number = {4}, pages = {325-332}, doi = {10.1016/0005-7967(89)90002-8}, pmid = {2775142}, issn = {0005-7967}, mesh = {Adult ; Anxiety/*physiopathology ; Fear/*physiology ; Female ; Humans ; Hyperventilation/*psychology ; Male ; Panic/*physiology ; Syndrome ; }, abstract = {In this study, we examined the effects of anxiety sensitivity on the response to hyperventilation in college students with and without a history of spontaneous panic attacks. Reiss et al.'s (Behav. Res. Ther. 24, 1-8, 1986) Anxiety Sensitivity Index and Norton et al.'s (Behav. Ther. 17, 239-252, 1986) Panic Attack Questionnaire were used to select Ss. Following five min of voluntary hyperventilation, high anxiety sensitivity Ss reported more anxiety and more hyperventilation sensations than did low anxiety sensitivity Ss. A history of panic was only associated with enhanced responding to hyperventilation in Ss with high anxiety sensitivity; low anxiety sensitivity Ss who had experience with panic were no more responsive than low anxiety sensitivity Ss who had never had a panic attack. These findings suggest that high anxiety sensitivity may be a crucial determinant of panic attacks provoked by biological challenges (e.g. hyperventilation, sodium lactate infusion).}, } @article {pmid2648436, year = {1989}, author = {Matt, GE}, title = {Decision rules for selecting effect sizes in meta-analysis: a review and reanalysis of psychotherapy outcome studies.}, journal = {Psychological bulletin}, volume = {105}, number = {1}, pages = {106-115}, doi = {10.1037/0033-2909.105.1.106}, pmid = {2648436}, issn = {0033-2909}, mesh = {Humans ; *Meta-Analysis as Topic ; *Psychotherapy ; Research Design ; }, abstract = {This study deals with some of the judgmental factors involved in selecting effect sizes from within the studies that enter a meta-analysis. Particular attention is paid to the conceptual redundancy rule that Smith, Glass, and Miller (1980) used in their study of the effectiveness of psychotherapy for deciding which effect sizes should and should not be counted in determining an overall effect size. Data from a random sample of 25 studies from Smith et al.'s (1980) population of psychotherapy outcome studies were first recoded and then reanalyzed meta-analytically. Using the conceptual redundancy rule, three coders independently coded effect sizes and identified more than twice as many of them per study as did Smith et al. Moreover, the treatment effect estimates associated with this larger sample of effects ranged between .30 and .50, about half the size claimed by Smith et al. Analyses of other rules for selecting effect sizes showed that average effect estimates also varied with these rules. Such results indicate that the average effect estimates derived from meta-analyses may depend heavily on judgmental factors that enter into how effect sizes are selected within each of the individual studies considered relevant to a meta-analysis.}, } @article {pmid2591740, year = {1989}, author = {Arana, A and Zaragoza, P and Rodellar, C and Amorena, B}, title = {Blood biochemical polymorphisms as markers for genetic characteristics of wild Spanish and domestic rabbits.}, journal = {Genetica}, volume = {79}, number = {1}, pages = {1-9}, pmid = {2591740}, issn = {0016-6707}, mesh = {Animals ; Animals, Domestic/genetics ; Animals, Wild/genetics ; Blood Proteins/*genetics ; Female ; Gene Frequency ; Genetic Markers/blood ; *Genetics, Population ; Inbreeding ; Male ; Phenotype ; Polymorphism, Genetic/*genetics ; Rabbits/blood/*genetics ; Spain ; }, abstract = {Seventeen blood proteins were studied in a sample of 412 Spanish wild rabbits and in 598 domestic rabbits belonging to various breeds. The wild rabbit populations showed a high level of genetic polymorphism. Six loci were monomorphic, while the remaining ten loci were segregating for at least two alleles. Two of the loci that were polymorphic in the wild rabbits were monomorphic in the domestic ones. Wright's inbreeding coefficient in the total Spanish wild rabbit population was F = 5.66, indicating subdivision of the total population. Inbreeding coefficients, estimated by Kidd et al.'s method (Anim. Blood Grps, Biochem. Genet. 11: 21-38), differed significantly from zero, being 15.62%, in wild rabbits and 6-12% in domestic breeds, indicating consanguinity. Genetic distances between wild rabbit populations showed that factors other than geographic distance (e.g., bottlenecks, barriers such as rivers, mountains, etc.) may explain the result that a northern population forms a cluster with two central populations whereas the northeastern populations form a different cluster with another central population. Populations of the first cluster are more closely related to the captive populations than others. There are three population clusters of domestic rabbits, namely (1) New Zealand White and a hybrid combination; (2) Spanish Common, Butterfly, Burgundy, and Californian; and (3) Spanish Giant.}, } @article {pmid3225480, year = {1988}, author = {Nakai, Y and Nakayama, T and Nagano, T and Shibamoto, T and Ohara, A and Ezaki, Y and Shimizu, T and Tamura, H and Ozawa, M}, title = {[Primary carcinoma of the fallopian tube: its clinical aspects and problems in the postoperative staging system].}, journal = {Nihon Sanka Fujinka Gakkai zasshi}, volume = {40}, number = {10}, pages = {1499-1505}, pmid = {3225480}, issn = {0300-9165}, mesh = {Adult ; Combined Modality Therapy ; Fallopian Tube Neoplasms/epidemiology/*pathology/therapy ; Female ; Humans ; Infertility, Female/complications ; Middle Aged ; Neoplasm Staging ; Postoperative Period ; Risk Factors ; }, abstract = {Clinical features of primary carcinoma of the fallopian tube were studied in 13 patients treated in Osaka National Hospital between 1961 and 1987. The relationship between clinical staging and prognosis in each patient is discussed. The incidence of this disease among all cases of malignant tumor in the gynecological department during the same 27-year period was 0.18%. The mean age of the patients was 50.7 years. Twelve patients (92%) were within the age range from 41 to 59 years, the most common age of onset. Six patients (46%) were nulligravida and 9 (69%) were nulliparous, suggesting infertility as a possible important risk factor for the disease. None of the six who underwent cervical cytodiagnosis showed tumor cells. Three were positive for cytodiagnosis by aspiration biopsy. The concomitant use of many drugs, including CDDP given postoperatively to 2 patients with advanced disease, was markedly effective. The radiotherapy carried out in 4 patients was ineffective. When the patients were staged according to the classifications of Dodson et al. and Schiller et al., there was no difference between these classifications in advanced cases. However, Dodson et al.'s classification was considered unsuitable for patients with early-stage cancerous lesions localized in the fallopian tube, while that of Schiller et al. was considered to be superior in evaluating prognosis.}, } @article {pmid3414849, year = {1988}, author = {Dworkin, RH and Lenzenweger, MF and Moldin, SO and Skillings, GF and Levick, SE}, title = {A multidimensional approach to the genetics of schizophrenia.}, journal = {The American journal of psychiatry}, volume = {145}, number = {9}, pages = {1077-1083}, doi = {10.1176/ajp.145.9.1077}, pmid = {3414849}, issn = {0002-953X}, mesh = {Adult ; Age Factors ; *Diseases in Twins ; Female ; Humans ; Male ; Psychiatric Status Rating Scales ; Risk Factors ; Schizophrenia/diagnosis/*genetics ; *Schizophrenic Psychology ; Sex Factors ; Social Adjustment ; Twins, Monozygotic ; }, abstract = {To determine which dimensions of psychopathology are associated with a greater liability to develop schizophrenia, the authors examined the case histories of 151 monozygotic probands from five twin studies. Proband twins from pairs concordant for schizophrenia had greater numbers of negative symptoms, poorer premorbid adjustment, fewer paranoid symptoms, and earlier ages at onset than probands from discordant pairs. In discriminant analyses, negative symptoms, premorbid social competence, and paranoid symptoms each contributed to the discrimination between concordant and discordant pairs. These results provide support for Strauss et al.'s suggestion that these three types of symptoms reflect three different functional processes in the development of schizophrenia.}, } @article {pmid3062128, year = {1988}, author = {Sweeney, J and Bradbard, MR}, title = {Mothers' and fathers' changing perceptions of their male and female infants over the course of pregnancy.}, journal = {The Journal of genetic psychology}, volume = {149}, number = {3}, pages = {393-404}, doi = {10.1080/00221325.1988.10532167}, pmid = {3062128}, issn = {0022-1325}, mesh = {Fathers/*psychology ; Female ; Humans ; Infant, Newborn/*psychology ; Male ; Mothers/*psychology ; Pregnancy/*psychology ; Sex Determination Analysis ; Sex Factors ; *Social Perception ; Ultrasonography ; }, abstract = {Twelve pregnant women and their spouses who had undergone ultrasonography and knew their child's gender were compared with 12 pregnant women and their spouses who had undergone ultrasonography but did not know their child's gender. Parents were interviewed (a) prior to receiving the ultrasound, (b) immediately after the ultrasound, and (c) following their infant's birth. Using the adjectives rating scales, and replicating the procedures developed by Rubin, Provenzano, and Luria (1974), parents' perceptions of their infants were measured. ANOVA results indicated that parents viewed their infants to be softer, finer, littler, cuddlier, easier, calmer, more inactive, more beautiful, more awkward, quieter, weaker, and somewhat more delicate following birth than during the preceding measurement period(s). Mothers viewed their infants to be softer, more nervous, more fussy, more excitable, and more noisy than did fathers. Supporting Rubin et al.'s (1974) findings, several differences emerged between parents' perceptions of boys and girls, particularly by the time the infants were born. Following birth, parents perceived girls to be finer, smaller, less coordinated, quieter, weaker, and more delicate than boys. No differences were found as a result of parents being informed of their infants' gender prior to birth.}, } @article {pmid3168622, year = {1988}, author = {Kail, R}, title = {Reply to Stigler, Nusbaum, and Chalip.}, journal = {Child development}, volume = {59}, number = {4}, pages = {1154-1157}, pmid = {3168622}, issn = {0009-3920}, support = {HD 19947/HD/NICHD NIH HHS/United States ; }, mesh = {Child Development ; Humans ; Learning ; Memory ; *Models, Psychological ; Rotation ; Space Perception ; Statistics as Topic ; *Transfer, Psychology ; }, abstract = {In this article, I show that many of Stigler et al.'s criticisms of my 1986 article are incorrect or based on assumptions that are implausible. I agree with their conclusion, however, that theories of cognitive development must include both domain-specific and general processes.}, } @article {pmid3378417, year = {1988}, author = {Hyler, SE and Lyons, M}, title = {Factor analysis of the DSM-III personality disorder clusters: a replication.}, journal = {Comprehensive psychiatry}, volume = {29}, number = {3}, pages = {304-308}, doi = {10.1016/0010-440x(88)90053-3}, pmid = {3378417}, issn = {0010-440X}, mesh = {Adolescent ; Adult ; Aged ; Factor Analysis, Statistical ; Female ; Humans ; Male ; Middle Aged ; Personality Disorders/*diagnosis ; Psychiatric Status Rating Scales ; }, abstract = {The authors describe the replication of Kass et al.'s study where a factor analysis of scaled ratings of DSM-III personality disorders yielded groupings similar to those described in DSM-III. In this replication the authors used scaled ratings from a nationwide sample of psychiatrists on 358 patients. The authors conclude that this replication lends additional support for the DSM-III (now DSM-III-R) approach towards grouping personality disorders into three (or four) clusters.}, } @article {pmid3398039, year = {1988}, author = {Newton, JT and Sturmey, P}, title = {The Aberrant Behaviour Checklist: a British replication and extension of its psychometric properties.}, journal = {Journal of mental deficiency research}, volume = {32 (Pt 2)}, number = {}, pages = {87-92}, doi = {10.1111/j.1365-2788.1988.tb01394.x}, pmid = {3398039}, issn = {0022-264X}, mesh = {Adult ; England ; Factor Analysis, Statistical ; Female ; Humans ; Intellectual Disability/*psychology ; Male ; Neuropsychological Tests/*methods ; Psychometrics ; Residential Facilities ; }, abstract = {The Aberrant Behaviour Checklist was administered to 209 British mentally handicapped adults in two large residential facilities. This sample included a substantial proportion (45%) of non-ambulant people not included in previous studies. The five-factor solution originally reported by Aman et al. (1985a) was replicated using both four-point ratings and dichotomously recoded rating. For both methods of scoring, the five scales derived from Aman et al.'s original factor analysis remained highly internally consistent. Dichotomously coded ratings may offer the advantage over four-point ratings of retaining the same factor structure with better reliability.}, } @article {pmid3359870, year = {1988}, author = {Diamond, A}, title = {Abilities and neural mechanisms underlying AB performance.}, journal = {Child development}, volume = {59}, number = {2}, pages = {523-527}, pmid = {3359870}, issn = {0009-3920}, mesh = {Amnesia/*physiopathology ; Animals ; Frontal Lobe/physiology ; Hippocampus/physiology ; Humans ; Infant ; Inhibition, Psychological/physiology ; Macaca mulatta ; Memory/*physiology ; Proactive Inhibition/physiology ; *Psychology, Child ; Space Perception/*physiology ; }, abstract = {Schacter, Moscovitch, Tulving, McLachlan, and Freedman propose that infants may make the AB error because of immaturity of the memory system damaged in amnesia (e.g., the hippocampus). They contrast this with the proposal that infants may make the AB error because of immaturity of the frontal lobe system (Diamond; Diamond & Goldman-Rakic). Schacter et al.'s choice of subjects, however, did not permit a test of these 2 proposals, and characteristics of their task, such as length of delay, make comparison with infants difficult. Schacter et al. discuss sensitivity to proactive interference as a possible explanation for the AB error, but sensitivity to PI is more closely associated with frontal lobe damage than with amnesia. Schacter et al. associate perseveration with immaturity or damage to the frontal lobe; it is suggested here that this is better characterized as lack of inhibitory control. Tasks that are most likely to require frontal cortex function are those that demand both short-term memory and inhibitory control. AB is an excellent example of such a task.}, } @article {pmid3287985, year = {1988}, author = {Sher, KJ and Alterman, AI}, title = {The HK/MBD questionnaire: replication and validation of distinct factors in a nonclinical sample.}, journal = {Alcoholism, clinical and experimental research}, volume = {12}, number = {2}, pages = {233-238}, doi = {10.1111/j.1530-0277.1988.tb00186.x}, pmid = {3287985}, issn = {0145-6008}, support = {AA6182/AA/NIAAA NIH HHS/United States ; }, mesh = {Adult ; Alcoholism/complications/genetics/*psychology ; Attention Deficit Disorder with Hyperactivity/*complications ; Behavior ; Humans ; Male ; Personality Tests ; Smoking ; Substance-Related Disorders/complications/psychology ; Surveys and Questionnaires ; }, abstract = {Although Tarter et al.'s (1977) HK/MBD questionnaire has been found useful in subtyping populations of clinical alcoholics, its potential utility in nonclinical populations has yet to be determined. The current study examined the family history, personality, and substance use/abuse correlates of Tarter et al.'s HK/MBD questionnaire and factor analytically derived subscales (Alterman and McLellan, 1986) in a nonclinical sample of 580 young, adult males. In addition, a factor analysis of the HK/MBD questionnaire was undertaken to assess the extent to which the factor structure determined on a clinical alcoholic sample replicates in a nonclinical sample. Results indicated that each of the HK/MBD subscales showed relatively unique patterns of correlations with the various personality measures employed suggesting that they are measuring separate constructs. Perhaps of greatest importance, the HK/MBD items that appear to be of greatest relevance for understanding substance use/abuse are those related to antisocial behavior. Finally, the factor structure of the HK/MBD questionnaire in the nonclinical sample was found to be quite similar to the structure obtained in a clinical sample. These results demonstrate the multidimensional structure of the HK/MBD questionnaire and the utility of using the more homogeneous subscales in research with both clinical and nonclinical samples.}, } @article {pmid3165152, year = {1988}, author = {Kano, Y and Ohta, M and Nagai, Y and Yokota, K and Shimizu, Y}, title = {Tourette's disorder coupled with infantile autism: a prospective study of two boys.}, journal = {The Japanese journal of psychiatry and neurology}, volume = {42}, number = {1}, pages = {49-57}, doi = {10.1111/j.1440-1819.1988.tb01955.x}, pmid = {3165152}, issn = {0912-2036}, mesh = {Adult ; Autistic Disorder/*psychology ; Child Development ; Humans ; Japan ; Male ; Social Adjustment ; Stereotyped Behavior ; Tourette Syndrome/*psychology ; }, abstract = {In a longitudinal study, two boys in the Outpatient Psychiatric Clinic at Tokyo University were found to exhibit Tourette's disorder in addition to the original diagnoses of infantile autism. This paper addresses problems of applying the diagnostic criteria of DSM-III in terms of voluntary tic suppression in diagnosing patients with both disorders. Differences between motor tics and stereotyped movements in patients with both infantile autism and Tourette's disorder have been clearly distinguished. This may enable us to identify more autistic individuals with Tourette's disorder by focusing on these differences. In contrast to Burd et al.'s findings and implications, these two boys have not manifested spurts in language and social relationships nor have their conditions significantly improved, despite the development of Tourette's disorder.}, } @article {pmid3361605, year = {1988}, author = {Sturmey, P and Carlsen, A and Crisp, AG and Newton, JT}, title = {A functional analysis of multiple aberrant responses: a refinement and extension of Iwata et al.'s (1982) methodology.}, journal = {Journal of mental deficiency research}, volume = {32 (Pt 1)}, number = {}, pages = {31-46}, doi = {10.1111/j.1365-2788.1988.tb01386.x}, pmid = {3361605}, issn = {0022-264X}, mesh = {Adult ; Behavior Therapy/*methods ; *Conditioning, Operant ; Education of Persons with Intellectual Disabilities ; Female ; Humans ; Intellectual Disability/*psychology/therapy ; Male ; Play and Playthings ; Psychological Tests ; Self Mutilation/*psychology ; *Social Environment ; *Stereotyped Behavior ; }, abstract = {This study extends an operant methodology for the analysis of variables which control aberrant responses displayed by mentally handicapped people. The proportion of time spent in individual, stereotyped topographies by three profoundly mentally handicapped subjects was observed by momentary time-sampling whilst they were repeatedly exposed to four analogue environments: Alone, Social Disapproval, Academic Demand and Unstructured Play. Two of the three subjects showed replicable effects of the analogue environments. One subject showed evidence of an interaction between stereotyped topography and type of analogue environment. This study shows that the operant methodology of Iwata et al. (1982), originally developed with self-injurious responses, can be successfully refined and extended to the analysis of a wider range of aberrant topographies.}, } @article {pmid3285615, year = {1988}, author = {Beck, T and Höckel, M and Friese, K}, title = {[Degree of placental maturity and histopathologic finding: clinical prospective studies of a sample of term births and premature births].}, journal = {Zeitschrift fur Geburtshilfe und Perinatologie}, volume = {192}, number = {1}, pages = {24-32}, pmid = {3285615}, issn = {0300-967X}, mesh = {Chorionic Villi/pathology ; Female ; Gestational Age ; Humans ; Infant, Newborn ; Infant, Premature, Diseases/*pathology ; Obstetric Labor Complications/pathology ; Placenta/*pathology ; Pregnancy ; Pregnancy Complications/pathology ; *Ultrasonography ; }, abstract = {By analogy with Grannum et al.'s sonographic classification of the placenta (1979), macroscopic observation of the cut surfaces of the afterbirth enables the extent of placental segmentation to be determined and macroscopic maturity to be established in accordance with sonographic findings. Out of a total of 767 clinically-prospectively documented obstetrical cases, 674 were identified as term births and 93 as premature. For the purposes of comparison they were subdivided into two groups: term births with stage 0 to II and stage III maturity; and premature births with stage 0 to II and stage III maturity. Proceeding from this morphological classification and grouping, the clinical data, such as age of the mother, parity, gravidity, diseases during pregnancy, premature labour, type of delivery, fetal outcome, and biometric data of the newborn, as well as histologic findings regarding villous maturity, were recorded and statistically analyzed. The findings revealed no significant differences between term births with stage III maturity and those in the control group of placentas with stage 0 to II maturity and the same gestation time. Therefore, stage III maturity at term corresponds chronopathologically to a normal temporal development of fetomaternal flow units of the mature human placenta at term and does not imply any perinatological risk. Histopathologically, placentas with stage III maturity manifest a significantly advanced degree of villous maturity, with lower mean placental weight as the morphological correlate to threshold placental function, which is reflected in the clinical data of perinatological complications. Therefore, premature detection of a stage III placenta before term indicates a risk that should be kept in mind in the overall concept of prenatal monitoring parameters.}, } @article {pmid3227384, year = {1988}, author = {Mackenbach, JP and Looman, CW and Kunst, AE and Habbema, JD and van der Maas, PJ}, title = {Post-1950 mortality trends and medical care: gains in life expectancy due to declines in mortality from conditions amenable to medical intervention in The Netherlands.}, journal = {Social science & medicine (1982)}, volume = {27}, number = {9}, pages = {889-894}, doi = {10.1016/0277-9536(88)90278-x}, pmid = {3227384}, issn = {0277-9536}, mesh = {*Cause of Death ; Female ; Health Resources/*trends ; Humans ; Infant ; Infant Mortality/trends ; Infant, Newborn ; Life Expectancy/*trends ; Male ; Maternal Mortality/trends ; *Mortality ; Netherlands ; Pregnancy ; Primary Health Care/*trends ; }, abstract = {In order to assess the impact of medical care innovations on post-1950 mortality in The Netherlands, we analysed trends in mortality from a selection of conditions suggested by Rutstein et al.'s lists of "unnecessary untimely mortality". This selection covers 11 types of innovation, and includes 35 conditions which have become amenable to medical care. Loglinear regression analysis shows that for most of these conditions mortality declined during each of two subperiods (1950-1968; 1969-1984). Mortality decline accelerated in the second subperiod for many conditions. Reductions in mortality from these conditions between 1950/54 and 1980/84 added 2.96 and 3.95 years to life expectancy at birth of Dutch males and Dutch females respectively. A priori evidence indicates that these mortality reductions are due to some extent to 'spontaneous' incidence declines. Although the exact contribution of medical care innovations to these changes in mortality thus cannot be determined, the impact of medical care on post-1950 mortality in The Netherlands could well have been substantial.}, } @article {pmid3138428, year = {1988}, author = {Saitou, N}, title = {Property and efficiency of the maximum likelihood method for molecular phylogeny.}, journal = {Journal of molecular evolution}, volume = {27}, number = {3}, pages = {261-273}, pmid = {3138428}, issn = {0022-2844}, mesh = {Biological Evolution ; DNA/genetics ; *Models, Genetic ; *Phylogeny ; Probability ; }, abstract = {The maximum likelihood (ML) method for constructing phylogenetic trees (both rooted and unrooted trees) from DNA sequence data was studied. Although there is some theoretical problem in the comparison of ML values conditional for each topology, it is possible to make a heuristic argument to justify the method. Based on this argument, a new algorithm for estimating the ML tree is presented. It is shown that under the assumption of a constant rate of evolution, the ML method and UPGMA always give the same rooted tree for the case of three operational taxonomic units (OTUs). This also seems to hold approximately for the case with four OTUs. When we consider unrooted trees with the assumption of a varying rate of nucleotide substitution, the efficiency of the ML method in obtaining the correct tree is similar to those of the maximum parsimony method and distance methods. The ML method was applied to Brown et al.'s data, and the tree topology obtained was the same as that found by the maximum parsimony method, but it was different from those obtained by distance methods.}, } @article {pmid3503665, year = {1987}, author = {Verleger, R}, title = {Sequential effects on P3 in a counting task: a partial replication.}, journal = {Biological psychology}, volume = {25}, number = {3}, pages = {221-246}, doi = {10.1016/0301-0511(87)90049-4}, pmid = {3503665}, issn = {0301-0511}, mesh = {Adolescent ; Adult ; Analysis of Variance ; Choice Behavior/*physiology ; Electrooculography ; *Evoked Potentials, Auditory ; Humans ; Male ; Middle Aged ; Pitch Perception/*physiology ; Probability ; Reaction Time ; }, abstract = {High and low tones were presented in random order, and the high tones had to be counted. It was intended to replicate the sequential effects on P3 reported by Squires et al. (1976, 1977) and to test by means of an ANOVA approach how each one of the preceding four tones contributes to these sequential effects. However, results deviated from those studies: (1) P3s were generally somewhat larger with target tones than with nontargets; (2) Squires et al.'s (1976, 1977) sequential effects were replicated for nontargets, but were more or less reversed for targets. The preceding sequence was found also to exert influence on prestimulus baselines, N1, and EOG. It is suggested that target effects constitute the rule rather than the exception and that sequential effects on P3 may be altered by subtle differences of subjects' sets, similarly to sequential effects on choice reaction times.}, } @article {pmid3484335, year = {1987}, author = {Hockenberry, SL and Billingham, RE}, title = {Sexual orientation and boyhood gender conformity: development of the Boyhood Gender Conformity Scale (BGCS).}, journal = {Archives of sexual behavior}, volume = {16}, number = {6}, pages = {475-492}, pmid = {3484335}, issn = {0004-0002}, mesh = {Adolescent ; Adult ; Aged ; *Child Behavior ; *Gender Identity ; Homosexuality ; Humans ; *Identification, Psychological ; Male ; Middle Aged ; Personality Inventory ; Social Conformity ; }, abstract = {Two hundred twenty-five [corrected] respondents (109 [corrected] heterosexuals and 116 [corrected] homosexuals) completed a survey containing a 20-item Boyhood Gender Conformity Scale (BGCS). This scale was largely composed of edited and abridged gender items from Part A of Freund et al.'s Feminine Gender Identity Scale (FGIS-A) and Whitam's "childhood indicators." The combined scale was developed in an attempt to obtain a reliable, valid, and potent discriminating instrument for accurately classifying adult male respondents for sexual orientation on the basis of their reported boyhood gender conformity or nonconforming behavior and identity. In addition, 33% of these respondents were administered the original FGIS-A and Whitam inventory during a 2-week test-retest analysis conducted to determine the validity and reliability of the new instrument. All the original items significantly discriminated between heterosexual and homosexual respondents. From these a 13-item function and a 5-item function proved to be the most powerful discriminators between the two groups. Significant correlations between each of the three scales and a very high test-retest correlation coefficient supported the reliability and validity assumption for the BGCS. The conclusion was made that the five-item function (playing with boys, preferring [corrected] boys' games, imagining self as sports figure, reading adventure and sports stories, considered a "sissy") was the most potent and parsimonious discriminator among adult males for sexual orientation. It was similarly noted that the absence of masculine behaviors and traits appeared to be a more powerful predictor of later homosexual orientation than the traditionally feminine or cross-sexed traits and behaviors.}, } @article {pmid3447015, year = {1987}, author = {Saitou, N and Nei, M}, title = {The neighbor-joining method: a new method for reconstructing phylogenetic trees.}, journal = {Molecular biology and evolution}, volume = {4}, number = {4}, pages = {406-425}, doi = {10.1093/oxfordjournals.molbev.a040454}, pmid = {3447015}, issn = {0737-4038}, mesh = {Animals ; Biological Evolution ; Biometry ; *Models, Genetic ; *Phylogeny ; Ranidae/*genetics ; }, abstract = {A new method called the neighbor-joining method is proposed for reconstructing phylogenetic trees from evolutionary distance data. The principle of this method is to find pairs of operational taxonomic units (OTUs [= neighbors]) that minimize the total branch length at each stage of clustering of OTUs starting with a starlike tree. The branch lengths as well as the topology of a parsimonious tree can quickly be obtained by using this method. Using computer simulation, we studied the efficiency of this method in obtaining the correct unrooted tree in comparison with that of five other tree-making methods: the unweighted pair group method of analysis, Farris's method, Sattath and Tversky's method, Li's method, and Tateno et al.'s modified Farris method. The new, neighbor-joining method and Sattath and Tversky's method are shown to be generally better than the other methods.}, } @article {pmid2440215, year = {1987}, author = {Travis, WD and Wold, LE}, title = {Immunoperoxidase staining of fine needle aspiration specimens previously stained by the Papanicolaou technique.}, journal = {Acta cytologica}, volume = {31}, number = {4}, pages = {517-520}, pmid = {2440215}, issn = {0001-5547}, mesh = {*Biopsy, Needle ; Carcinoma, Small Cell/analysis/pathology ; Colonic Neoplasms/analysis/pathology ; Humans ; *Immunoenzyme Techniques ; Lung Neoplasms/analysis/pathology ; Male ; Neoplasms/analysis/*pathology ; Prostatic Neoplasms/analysis/pathology ; Staining and Labeling ; }, abstract = {The use of immunoperoxidase techniques was investigated in 21 fine needle aspiration (FNA) cytology smears that had been previously stained by the Papanicolaou technique. The retrospectively selected slides were destained before applying the immunostain, utilizing antisera to calcitonin, prostatic acid phosphatase (PrAP), prostate-specific antigen (PSA), alpha-lactalbumin (AL), S-100 protein (S-100), carcinoembryonic antigen (CEA), common leukocyte antigen (LA), epithelial membrane antigen (EMA) and alpha-fetoprotein (AFP). Positive results were obtained with six of nine small-cell carcinomas of the lung stained with EMA, all three colonic carcinomas stained with CEA, one of two prostatic carcinomas stained with PSA and PrAP, one of two lymphomas stained with LA and the one medullary thyroid carcinoma stained with calcitonin. Negative staining results were observed in the one melanoma stained with S-100, the two breast carcinomas stained with AL and the one hepatocellular carcinoma stained with AFP. These results indicate that immunostaining can be a helpful diagnostic tool in diagnosing some fine needle aspirates using smears previously stained with the Papanicolaou stain.}, } @article {pmid3572534, year = {1987}, author = {Matsuda, H and Nakai, H and Jovkar, S and Diksic, M and Evans, AC and Meyer, E and Redies, C and Yamamoto, YL}, title = {Alternative approach to estimate lumped constant in the deoxyglucose model: simulation and validation.}, journal = {Journal of nuclear medicine : official publication, Society of Nuclear Medicine}, volume = {28}, number = {4}, pages = {471-480}, pmid = {3572534}, issn = {0161-5505}, mesh = {Animals ; *Brain Chemistry ; Cats ; Computers ; Deoxy Sugars/*metabolism ; Deoxyglucose/*metabolism ; Female ; Glucose/metabolism ; Kinetics ; Male ; Mathematics ; Models, Biological ; }, abstract = {An alternative method of estimating the lumped constant (LC) in the deoxyglucose model was developed. The LC was estimated using data obtained during the first 10 min after injection of the tracer by a nonlinear least-squares (NLSQ) method. The method does not require a constant plasma concentration. This approach was evaluated in a computer simulation by adding different levels of noise and considering various input functions. Errors in the estimated LC in this and Sokoloff et al.'s conventional method were compared. We found that the approach proposed here results in more reliable estimates of LC. The study in completed in a shorter experimental period, and any shape of the input function can be used. The new technique was then applied to measure whole brain LC and rate constants in cat brain for 2-[18F]fluoro-2-deoxy-D-glucose (2-[18F]FDG). Measured mean value (+/-s.e.m.) for the whole brain LC = 0.443 +/- 0.012 (N = 7), for the whole brain k2* = 0.124 +/- 0.009 and k3* = 0.024 +/- 0.001 (N = 7).}, } @article {pmid3447006, year = {1987}, author = {Sourdis, J and Krimbas, C}, title = {Accuracy of phylogenetic trees estimated from DNA sequence data.}, journal = {Molecular biology and evolution}, volume = {4}, number = {2}, pages = {159-166}, doi = {10.1093/oxfordjournals.molbev.a040432}, pmid = {3447006}, issn = {0737-4038}, mesh = {Base Sequence ; DNA/*genetics ; *Models, Genetic ; Nucleotides/analysis ; *Phylogeny ; }, abstract = {The relative merits of four different tree-making methods in obtaining the correct topology were studied by using computer simulation. The methods studied were the unweighted pair-group method with arithmetic mean (UPGMA), Fitch and Margoliash's (FM) method, thd distance Wagner (DW) method, and Tateno et al.'s modified Farris (MF) method. An ancestral DNA sequence was assumed to evolve into eight sequences following a given model tree. Both constant and varying rates of nucleotide substitution were considered. Once the DNA sequences for the eight extant species were obtained, phylogenetic trees were constructed by using corrected (d) and uncorrected (p) nucleotide substitutions per site. The topologies of the trees obtained were then compared with that of the model tree. The results obtained can be summarized as follows: (1) The probability of obtaining the correct rooted or unrooted tree is low unless a large number of nucleotide differences exists between different sequences. (2) When the number of nucleotide substitutions per sequence is small or moderately large, the FM, DW, and MF methods show a better performance than UPGMA in recovering the correct topology. The former group of methods is particularly good for obtaining the correct unrooted tree. (3) When the number of substitutions per sequence is large, UPGMA is at least as good as the other methods, particularly for obtaining the correct rooted tree. (4) When the rate of nucleotide substitution varies with evolutionary lineage, the FM, DW, and MF methods show a better performance in obtaining the correct topology than UPGMA, except when a rooted tree is to be produced from data with a large number of nucleotide substitutions per sequence.(ABSTRACT TRUNCATED AT 250 WORDS)}, } @article {pmid3828600, year = {1987}, author = {Lobel, TE and Winch, GL}, title = {Neuroticism, anxiety and psychosocial development.}, journal = {The British journal of clinical psychology}, volume = {26 (Pt 1)}, number = {}, pages = {63-64}, doi = {10.1111/j.2044-8260.1987.tb00726.x}, pmid = {3828600}, issn = {0144-6657}, mesh = {Adult ; Anxiety Disorders/*psychology ; Female ; Humans ; Male ; Neurotic Disorders/*psychology ; *Personality Development ; Personality Tests ; *Social Adjustment ; }, abstract = {The current study investigated the relationship between resolution of Eriksonian crises and neuroticism and trait anxiety. Eighty-eight undergraduate students completed Constantinople's (1969) Inventory of Psychosocial Development (IPD), the Neuroticism scale from H.J. Eysenck & S.B.G. Eysenck's (1975) EPQ, and Spielberger et al.'s (1970) A-Trait scale. Correlations for both males and females were strongly significant and in the expected direction. Successful resolution of Eriksonian crises was negatively related to maladjustment, as successful resolvers had low anxiety and neuroticism scores. The relationship between adjustment and psychosocial development is discussed.}, } @article {pmid3768275, year = {1986}, author = {Williams, JM}, title = {Differences in reasons for taking overdoses in high and low hopelessness groups.}, journal = {The British journal of medical psychology}, volume = {59}, number = {3}, pages = {269-277}, doi = {10.1111/j.2044-8341.1986.tb02693.x}, pmid = {3768275}, issn = {0007-1129}, mesh = {Adolescent ; Adult ; Attitude to Death ; Female ; Humans ; Male ; Middle Aged ; *Motivation ; Poisoning/*psychology ; Psychological Tests ; Suicide, Attempted/*psychology ; }, abstract = {Thirty-five people admitted to hospital following deliberate self-harm by overdose were interviewed. Patients rated several 'reasons' for making the attempt on 0-10-point scales. The 'reasons' used were those derived by Bancroft and his associates (e.g. find out if someone loved me, make people understand how desperate I was feeling). The patients also completed Beck et al.'s Hopelessness Scale. High hopelessness was associated with an increased wish 'to die' and 'to get relief from a terrible state of mind' but high and low hopelessness did not differentiate between other reasons, even the traditionally 'manipulative' ones. The intercorrelations between reasons suggested that in low hopelessness interpersonal reasons were the most central constructs, whereas in the high hopelessness patients, the escape motive was the most central.}, } @article {pmid3760203, year = {1986}, author = {Watson, CG and Kucala, T and Manifold, V}, title = {A cross-validation of the Keane and Penk MMPI scales as measures of post-traumatic stress disorder.}, journal = {Journal of clinical psychology}, volume = {42}, number = {5}, pages = {727-732}, doi = {10.1002/1097-4679(198609)42:5<727::aid-jclp2270420508>3.0.co;2-4}, pmid = {3760203}, issn = {0021-9762}, mesh = {Combat Disorders/*diagnosis/psychology ; Humans ; *MMPI ; Male ; Psychometrics ; Stress Disorders, Post-Traumatic/*diagnosis ; Veterans/*psychology ; }, abstract = {The scores of DSM-III-diagnosed post-traumatic stress disorder (PTSD) patients (N = 116), psychiatric patients who did not meet the criteria, and normals (N = 19) on the Keane, Malloy, and Fairbank (1984) PTSD and Penk Combat scales for the MMPI were compared. The Keane scale discriminated PTSD-positive patients from normals at a substantial level of accuracy (omega 2 = .23; mean hit rate = 80.5%) and PTSD-positive from PTSD-negative patients at a more modest level (omega 2 = .09; mean hit rate = 64%). The scores of the PTSD-positive and PTSD-negative patients were considerably lower than those of Keane et al.'s (1984) samples, which suggests that local norms may be needed to facilitate their interpretation. The Penk Combat Intensity scale, which was correlated highly with the Keane scale, differentiated the PTSD-positive patients from both the normals and the PTSD-negative patients, but with less differentiating power (omega 2'S = .07 and .08). The Penk Combat Exposure scale did not separate the groups.}, } @article {pmid3444411, year = {1986}, author = {Nei, M and Gojobori, T}, title = {Simple methods for estimating the numbers of synonymous and nonsynonymous nucleotide substitutions.}, journal = {Molecular biology and evolution}, volume = {3}, number = {5}, pages = {418-426}, doi = {10.1093/oxfordjournals.molbev.a040410}, pmid = {3444411}, issn = {0737-4038}, mesh = {*Amino Acid Sequence ; Animals ; *Base Sequence ; *Biological Evolution ; Computer Simulation ; Globins/genetics ; Humans ; Mutation ; }, abstract = {Two simple methods for estimating the numbers of synonymous and nonsynonymous nucleotide substitutions are presented. Although they give no weights to different types of codon substitutions, these methods give essentially the same results as those obtained by Miyata and Yasunaga's and by Li et al.'s methods. Computer simulation indicates that estimates of synonymous substitutions obtained by the two methods are quite accurate unless the number of nucleotide substitutions per site is very large. It is shown that all available methods tend to give an underestimate of the number of nonsynonymous substitutions when the number is large.}, } @article {pmid3711448, year = {1986}, author = {Ruggero, MA and Robles, L and Rich, NC}, title = {Cochlear microphonics and the initiation of spikes in the auditory nerve: correlation of single-unit data with neural and receptor potentials recorded from the round window.}, journal = {The Journal of the Acoustical Society of America}, volume = {79}, number = {5}, pages = {1491-1498}, doi = {10.1121/1.393763}, pmid = {3711448}, issn = {0001-4966}, support = {NS12125/NS/NINDS NIH HHS/United States ; }, mesh = {Acoustic Stimulation ; Animals ; Auditory Threshold ; Chinchilla ; Cochlea/*physiology ; Hair Cells, Auditory/physiology ; Sound ; Vestibulocochlear Nerve/*physiology ; }, abstract = {On the basis of comparisons of responses of guinea pig ganglion cells and inner hair cells to intense low-frequency tones, Sellick et al. [Hear. Res. 7, 199-221 (1982)] have proposed that basal inner hair cells can be depolarized (and thus, VIII-N. spikes generated) by the extracellular microphonic generated during hyperpolarization of outer hair cells. VIII-N. data for the chinchilla have been presented that, to a first approximation, support such a hypothesis [Ruggero and Rich, J. Acoust. Soc. Am. 73, 2096-2108 (1983)]. However, an apparent discrepancy exists in our results, vis à vis Sellick et al.'s hypothesis, in that basal fiber near-threshold responses precede maximal negativity of the round window microphonic (i.e., maximal hyperpolarization of outer hair cells) by up to 90 degrees (but generally less than 45 degrees), depending on frequency. It is shown here that the discrepancy is resolved if certain nonlinear phase changes and overall distortion of the microphonic waveshapes, both of which occur at intense stimulus levels, are taken into account. It is also shown that compound action potentials (AP's), superimposed on the round window microphonics, can be identified at multiple times within each stimulus cycle, closely matching the near-threshold response phases of single-unit excitation. AP1 is nearly synchronous with the negative-to-positive transition of round window microphonics and with the excitation of fibers innervating apical-to-middle cochlear regions. AP2 is synchronous with the positive-to-negative transition of the microphonics and with the excitation of basal fibers. One or two other AP's probably reflect "peak splitting" in the responses of both basal and apical fibers.}, } @article {pmid3711345, year = {1986}, author = {Harding, TP and Lachenmeyer, JR}, title = {Family interaction patterns and locus of control as predictors of the presence and severity of anorexia nervosa.}, journal = {Journal of clinical psychology}, volume = {42}, number = {3}, pages = {440-448}, doi = {10.1002/1097-4679(198605)42:3<440::aid-jclp2270420306>3.0.co;2-h}, pmid = {3711345}, issn = {0021-9762}, mesh = {Adult ; Anorexia Nervosa/diagnosis/*psychology ; Attitude ; Eating ; *Family ; Female ; Humans ; *Internal-External Control ; *Interpersonal Relations ; Prognosis ; Psychological Tests ; Regression Analysis ; }, abstract = {Thirty female anorectics (mean age 26.4) and 30 female college student controls (mean age 25.3) completed a multidimensional locus of control scale, the Structural Family Interaction Scale, The Eating Attitudes Test, and a global clinical assessment measure. Three variables associated with Minuchin, Rosman, and Baker's (1978) family systems theory (overprotection, enmeshment, and rigidity) and one related to Bruch's (1973) theoretical position on anorexia nervosa (locus of control) were contrasted in terms of their relative effectiveness in predicting both the presence or absence and severity of the disorder. The best predictor of both measures in a series of regression and discriminant function analyses was locus of control orientation. The anorectics were significantly more external than the controls. The two groups did not differ on any of the family variables central to Minuchin et al.'s theory. The results support Bruch's contention that underlying anorexia nervosa is a sense of personal ineffectiveness.}, } @article {pmid3837827, year = {1985}, author = {Matsuki, Y}, title = {Dynamic stiffness of the isolated guinea-pig gall-bladder during contraction induced by cholecystokinin.}, journal = {Nihon Heikatsukin Gakkai zasshi}, volume = {21}, number = {6}, pages = {427-438}, doi = {10.1540/jsmr1965.21.427}, pmid = {3837827}, issn = {0374-3527}, mesh = {Acetylcholine/pharmacology ; Animals ; Calcium/pharmacology ; Cholecystokinin/*pharmacology ; Elasticity ; Gallbladder/drug effects/*physiology ; Guinea Pigs ; In Vitro Techniques ; Muscle Contraction/drug effects ; Viscosity ; }, abstract = {The visco-elastic properties of the isolated guinea-pig gall-bladder were investigated by the dynamic method. The sinusoidal volume changes (up to 0.2 ml) and the resulting sinusoidal pressure changes were displayed on the cathode ray oscilloscope, the volume being on abscissa and the pressure on ordinate. The frequencies of the sinusoidal change in volume were 0.17-0.5 Hz which were 10 times higher than those in Schoetz et al.'s work (Am. J. Physiol. 241: G376-G381, 1981). The dynamic pressure-volume relation of the resting gall-bladder was nearly linear, but showed the elliptical hysteresis loop during CCK- or ACh-induced contractions. If frequencies of the sinusoidal change in volume were increased to 1.7-3.3 Hz, the hysteresis loop for either relaxing or contracting gall-bladder became narrow and guiter-shaped. The dynamic stiffness, the slope of the hysteresis loop or the ratio of the maximum of pressure change to the maximum of volume change, increased in linear proportion to intraluminal pressure rise during contraction. The data could be analysed on the assumption that the visco-elastic property of the gall-bladder was explained by two Voigt models placed in series. The one indicated the property of the smooth muscle tissue, and it had low elastance at the resting state, or middle-grade elastance together with high viscous resistance at the contraction state. Another one had high elastance and low viscous resistance, and it was characterized by collagen fibers involved within the organ.}, } @article {pmid2934501, year = {1985}, author = {Salasoo, A and Feustel, TC and Shiffrin, RM}, title = {Memory codes and episodes in models of word identification: a reply to Johnston, van Santen, and Hale.}, journal = {Journal of experimental psychology. General}, volume = {114}, number = {4}, pages = {509-513}, doi = {10.1037//0096-3445.114.4.509}, pmid = {2934501}, issn = {0096-3445}, support = {MH-12717/MH/NIMH NIH HHS/United States ; R01-NS-21054/NS/NINDS NIH HHS/United States ; }, mesh = {Humans ; *Memory ; *Models, Psychological ; *Reading ; *Visual Perception ; }, abstract = {We suggest that the activation model of identification benefits for repeated words and pseudowords proposed by Johnston, van Santen, and Hale (1985) is a variant of our own code/episode model (Salasoo, Shiffrin, & Feustel, 1985), used to explain the temporary and long-lasting effects of repetitions. In particular, Johnston et al.'s X and Y factors may reflect the operation of episodic memory traces and codification, respectively. Computational processing models, we believe, are useful because their precision helps clarify otherwise fuzzy theoretical distinctions.}, } @article {pmid2934500, year = {1985}, author = {Johnston, JC and van Santen, JP and Hale, BL}, title = {Repetition effects in word and pseudoword identification: comment on Salasoo, Shiffrin, and Feustel.}, journal = {Journal of experimental psychology. General}, volume = {114}, number = {4}, pages = {498-508}, pmid = {2934500}, issn = {0096-3445}, mesh = {Humans ; *Memory ; *Models, Psychological ; *Reading ; *Visual Perception ; }, abstract = {Two recent articles by Feustel, Shiffrin, and Salasoo (1983) and Salasoo, Shiffrin, and Feustel (1985) argue that word identification is based on episodic memory as well as semantic (or "permanent, abstract") memory. The earlier article argued for separate processing stages affected by repetition (episodic memory) and lexicality (semantic memory). To account for the new finding that number of repetitions interacts with lexicality, the later article invokes the same two types of memory, operating in parallel rather than serially. We argue that Salasoo et al.'s data are compatible with a wide variety of competing theories, including some that do not involve episodic memory at all. We question the relevance of a complex formal model shown by the authors to account for the main trends in the data, because it makes little use of key properties of episodic memory. Furthermore, we show that two variants of a less complex model inspired by logogen theory fit the data as well or better than the model of Salasoo et al., using fewer free parameters. We argue that what is needed is not an existence proof that one particular complex model can fit a body of data, but experimental manipulations that successfully discriminate between broad classes of competing theories.}, } @article {pmid4068724, year = {1985}, author = {Maisto, SA and O'Farrell, TJ}, title = {Comment on the validity of Watson et al.'s "Do alcoholics give valid self-reports?".}, journal = {Journal of studies on alcohol}, volume = {46}, number = {5}, pages = {447-453}, doi = {10.15288/jsa.1985.46.447}, pmid = {4068724}, issn = {0096-882X}, mesh = {Alcohol Drinking ; Alcoholism/*psychology ; Humans ; Male ; Research Design ; *Self Disclosure ; }, abstract = {This is a critique of a study by Watson et al. on the validity of alcoholics' self-reports that suggested that clinical researchers and clinicians abandon the use of such data for now. It is shown, however, through an analysis of the rationale, procedures and data analyses reported by Watson et al., that their conclusions are not warranted. It is argued that the use of a situational and convergent validity approach to the collection and interpretation of self-report data is likely to continue to be a productive research and clinical strategy.}, } @article {pmid4044416, year = {1985}, author = {Charlet de Sauvage, R}, title = {Origins of eighth nerve unit response pattern in round window cap recordings.}, journal = {Hearing research}, volume = {18}, number = {2}, pages = {121-125}, doi = {10.1016/0378-5955(85)90003-6}, pmid = {4044416}, issn = {0378-5955}, mesh = {Acoustic Stimulation ; Animals ; Cochlea/*physiology ; Electric Stimulation ; Evoked Potentials, Auditory ; Guinea Pigs ; Perceptual Masking/physiology ; Round Window, Ear/*physiology ; Vestibulocochlear Nerve/*physiology ; }, abstract = {An experimental technique based on a combined electrical and acoustical stimulation of the cochlea (R. Charlet de Sauvage et al., 1983, J. Acoust. Soc. Am. 73, 616-627) allowing to record a close estimation of single unit contribution to the VIIIth nerve CAP has been recently proposed. D.C. Teas et al.'s (1962, J. Acoust. Soc. Am. 24, 1431-1459) theory about this pattern is that, due to conduction time in the internal auditory meatus, the propagated depolarisation partly differentiates in far-field recordings, giving rise to a specifically diphasic pattern. In order to evaluate Teas's hypothesis, 83 unit waveforms collected in 10 guinea pigs are analysed. Several reproducible peaks are identified. Latency and slope measurements are performed on these peaks. This data is processed, after identifying two homologous components which could combine in accordance with Teas's theory. The schematic pattern of a primary waveform is actually determined. Its relative amplitude on the two electrodes and the delay in the meatus are inferred. Results are in good agreement with published data. This is taken as an indirect validation of Teas's hypothesis.}, } @article {pmid3998161, year = {1985}, author = {Patrick, J}, title = {The relationship between the Wiggins' PSY scale and length of hospitalization: a re-examination.}, journal = {Journal of clinical psychology}, volume = {41}, number = {3}, pages = {386-388}, doi = {10.1002/1097-4679(198505)41:3<386::aid-jclp2270410313>3.0.co;2-d}, pmid = {3998161}, issn = {0021-9762}, mesh = {Adolescent ; Adult ; Aged ; Bipolar Disorder/diagnosis ; Depressive Disorder/diagnosis ; Female ; Humans ; *Length of Stay ; *MMPI ; Male ; Middle Aged ; Paranoid Disorders/diagnosis ; Psychometrics ; Psychotic Disorders/*diagnosis/psychology ; Schizophrenia/diagnosis ; }, abstract = {Peteroy, Pirrello, and Adams' (1982) findings on two Wiggins content scales, DEP and PSY, were re-examined. In contrast to Peteroy et al.'s results, both scales were found to relate significantly to length of psychiatric hospitalization (LOH) when a larger, more heterogeneous sampling (N = 362) was employed, together with a wider range of LOH values. This study demonstrates how attention to relevant sampling parameters in predictive validity studies can help to ensure that the utility of measures such as PSY is not misjudged.}, } @article {pmid2835574, year = {1985}, author = {Nei, M and Tajima, F}, title = {Evolutionary change of restriction cleavage sites and phylogenetic inference for man and apes.}, journal = {Molecular biology and evolution}, volume = {2}, number = {3}, pages = {189-205}, doi = {10.1093/oxfordjournals.molbev.a040345}, pmid = {2835574}, issn = {0737-4038}, mesh = {Animals ; Binding Sites ; *Biological Evolution ; Computer Simulation ; *DNA Restriction Enzymes ; Hominidae/genetics ; Humans ; Models, Genetic ; Phylogeny ; }, abstract = {A mathematical theory for the evolutionary change of restriction endonuclease cleavage sites is developed, and the probabilities of various types of restriction-site changes are evaluated. A computer simulation is also conducted to study properties of the evolutionary change of restriction sites. These studies indicate that parsimony methods of constructing phylogenetic trees often make erroneous inferences about evolutionary changes of restriction sites unless the number of nucleotide substitutions per site is less than 0.01 for all branches of the tree. This introduces a systematic error in estimating the number of mutational changes for each branch and, consequently, in constructing phylogenetic trees. Therefore, parsimony methods should be used only in cases where nucleotide sequences are closely related. Reexamination of Ferris et al.'s data on restriction-site differences of mitochondrial DNAs does not support Templeton's conclusions regarding the phylogenetic tree for man and apes and the molecular clock hypothesis. Templeton's claim that Nei and Li's method of estimating the number of nucleotide substitutions per site is seriously affected by parallel losses and loss-gains of restriction sites is also unsupported.}, } @article {pmid2982478, year = {1985}, author = {Falor, WH and Ward-Skinner, R and Wegryn, S}, title = {A 3p deletion in small cell lung carcinoma.}, journal = {Cancer genetics and cytogenetics}, volume = {16}, number = {2}, pages = {175-177}, doi = {10.1016/0165-4608(85)90012-3}, pmid = {2982478}, issn = {0165-4608}, mesh = {Aged ; Carcinoma, Small Cell/*genetics ; *Chromosome Deletion ; *Chromosomes, Human, 1-3 ; Humans ; Karyotyping ; Lung Neoplasms/*genetics ; Male ; }, abstract = {A specific chromosomal abnormality (3p del) was found in direct preparations from three small cell carcinomas of the lung: one primary tumor and two metastatic tumors in mediastinal lymph nodes. This lends support to Whang-Peng et al.'s [3] detection of the deletion in tissue cultures.}, } @article {pmid3986153, year = {1985}, author = {Wood, WD and Swanson, DA}, title = {Development and application of criteria for classes of psychotherapy based on patients' requests for service.}, journal = {The British journal of medical psychology}, volume = {58}, number = {1}, pages = {45-54}, doi = {10.1111/j.2044-8341.1985.tb02613.x}, pmid = {3986153}, issn = {0007-1129}, mesh = {Humans ; Mental Disorders/*therapy ; Mental Health Services ; *Patient Acceptance of Health Care ; Psychotherapy/*methods ; }, abstract = {Discrepancy frequently exists between the perspectives of psychotherapists and their patients about what problems and which patients are suitable for psychotherapy and how psychotherapy should be conducted. Lazare et al.'s (1972, 1975a) negotiated 'customer' approach attempts to correct this deficiency by providing mental health services that more fully take into account the specific service requests of patients. Lazare's 14 identified services were applied to develop profiles of each of four service types, including two classes of psychotherapy. Applying the criteria developed, 52.6 per cent of patients evaluated could be classified into one of four classes of service. Only two patients presented a pattern of service requests consistent with a broadly defined supportive psychotherapy. The three largest patient groups were then compared with respect to several classes of variables. Major differences were found between the non-psychotherapy group and the two psychotherapy groups, but not between the psychotherapy groups. Service requests of patients generally paralleled those perceived by the interviewers.}, } @article {pmid3980375, year = {1985}, author = {Grønlund, J and Christensen, P}, title = {Error due to dead-space admixture in single-breath method for estimation of pulmonary blood flow.}, journal = {Journal of applied physiology (Bethesda, Md. : 1985)}, volume = {58}, number = {3}, pages = {1034-1039}, doi = {10.1152/jappl.1985.58.3.1034}, pmid = {3980375}, issn = {8750-7587}, mesh = {Computers ; Humans ; Lung/physiology ; Models, Biological ; *Pulmonary Circulation ; Pulmonary Gas Exchange ; Respiration ; *Respiratory Dead Space ; }, abstract = {The single-breath method of Kim et al. (J. Appl. Physiol. 21: 1338-1344, 1966) for the estimation of pulmonary blood flow is based on a single-alveolus lung model for which an analytical relationship has been established between the kinetic behavior of the alveolar O2 and CO2 tensions and the pulmonary blood flow. The analysis is based on the assumption that the dead-space contribution to the expirate is negligible after expiration of a predefined volume. We have examined the influence of this assumption on the estimation of pulmonary blood flow by computer simulation in a lung model that incorporates deadspace contribution to the expirate. Data on the fractional contribution of the dead space to the expired gas were obtained from Tsunoda et al.'s study (J. Appl. Physiol. 32: 644-649, 1972) on the emptying pattern of normal adult lungs. The results show that failure to take account of the dead-space contribution can cause an underestimation in the pulmonary blood flow of greater than 30%. The error can be reduced by ignoring the first part of the expiration but only at the cost of an increase in the sensitivity of the single-breath method to measurement noise. This property of the system is demonstrated experimentally. The error due to dead-space admixture depends on the total volume of dead-space gas, the measurement noise, the pulmonary blood flow, and the emptying characteristics of the dead-space compartment during expiration. In normal subjects it is possible to optimize the experimental design so that the systematic error is less than 5% and the coefficient of variation is less than 10%.(ABSTRACT TRUNCATED AT 250 WORDS)}, } @article {pmid3982940, year = {1985}, author = {Pavlidis, GT}, title = {Erratic eye movements and dyslexia: factors determining their relationship.}, journal = {Perceptual and motor skills}, volume = {60}, number = {1}, pages = {319-322}, doi = {10.2466/pms.1985.60.1.319}, pmid = {3982940}, issn = {0031-5125}, mesh = {Dyslexia/*physiopathology ; *Eye Movements ; Humans ; Research Design/standards ; }, abstract = {Studies of dyslexia often produce contradictory results. Studies of eye movement are not an exception to this rule. The differences between Black, et al.'s 1984 and Pavlidis's 1981 eye-movement results are mainly due to differences in: (a) unquantifiable and variable criteria for selection of subjects, (b) incompatible experimental designs and procedures, (c) varying stimulus characteristics, and (d) major differences in the methods of data acquisition and analysis. The solution of these problems requires the establishment of quantifiable Research Diagnostic Criteria for Dyslexia and the use of compatible methods of data acquisition and analysis. The adoption of these standards would lead to a better understanding of dyslexia and would also make possible meaningful replications of major studies.}, } @article {pmid3971071, year = {1985}, author = {Hargreaves, IR}, title = {Attributional style and depression.}, journal = {The British journal of clinical psychology}, volume = {24 (Pt 1)}, number = {}, pages = {65-66}, doi = {10.1111/j.2044-8260.1985.tb01315.x}, pmid = {3971071}, issn = {0144-6657}, mesh = {Adult ; Depressive Disorder/diagnosis/*psychology ; Female ; Helplessness, Learned/*psychology ; Humans ; Internal-External Control ; Male ; Middle Aged ; Psychometrics ; *Set, Psychology ; }, abstract = {The study aimed to test the prediction, arising out of Abramson et al.'s (1978) reformulated learned helplessness model of depression, that depressed individuals have significantly different attributions about the causes of events from non-depressed individuals. No support was found for this hypothesis when comparing a depressed psychiatric sample with a matched normal group. Several hypotheses are offered to account for the failure to agree with previous studies.}, } @article {pmid4091157, year = {1985}, author = {Rounsaville, BJ and Gawin, F and Kleber, H}, title = {Interpersonal psychotherapy adapted for ambulatory cocaine abusers.}, journal = {The American journal of drug and alcohol abuse}, volume = {11}, number = {3-4}, pages = {171-191}, doi = {10.3109/00952998509016860}, pmid = {4091157}, issn = {0095-2990}, support = {1 R0 1 DA 03-467/DA/NIDA NIH HHS/United States ; K02 DA 00089-01/DA/NIDA NIH HHS/United States ; }, mesh = {Adult ; Cocaine/*adverse effects ; Grief ; Humans ; Impulsive Behavior/psychology ; Interpersonal Relations ; Male ; Marriage ; *Psychotherapy ; Recurrence ; Substance-Related Disorders/psychology/*rehabilitation ; }, abstract = {The authors describe the strategies and goals of Klerman et al.'s Interpersonal Psychotherapy (IPT) as revised for application to cocaine abusers. IPT is a brief, individual psychological treatment suitable for use by experienced psychotherapists. The goals are reduction or cessation of cocaine use and development of more productive strategies for dealing with social and interpersonal problems associated with the onset and perpetuation of cocaine use. The treatment has four definitive characteristics: (a) adherence to a medical model of psychiatric disorders; (b) focus on patient's difficulties in current interpersonal functioning; (c) brevity and emphasis on consistency of focus; and (d) use of an exploratory stance by the psychotherapist which is similar to that of supportive and exploratory psychotherapies. It is currently being used in combination with medications in a clinical trial evaluating the efficacy of desipramine, lithium carbonate, methylphenidate, and placebo as treatment for ambulatory cocaine abusers.}, } @article {pmid4077279, year = {1985}, author = {Hunter, J and Urbanowicz, MA and Yule, W and Lansdown, R}, title = {Automated testing of reaction time and its association with lead in children.}, journal = {International archives of occupational and environmental health}, volume = {57}, number = {1}, pages = {27-34}, pmid = {4077279}, issn = {0340-0131}, mesh = {Adolescent ; Child ; Computers ; Female ; Humans ; Intelligence Tests ; Lead/blood ; Lead Poisoning/blood/diagnosis/*psychology ; Male ; *Reaction Time ; Reading ; Risk ; }, abstract = {Following Needleman et al.'s (1979) report of a correlation between tooth lead estimates in children and reaction time as measured by Rodnick and Shakow's (1940) delayed reaction time paradigm, a version of the procedure with two delay periods of 3 s and 12 s was developed for automated presentation and scoring on a VIC-20 microcomputer. Data are presented from a study of 300 children aged 6-14 years. Mean reaction time over six trials for each delay period related in a curvilinear fashion with age, but no relationships were found with sex or intelligence. Age-adjusted reaction time related significantly with blood-lead levels, but accounted for only about 1 per cent of the variance. The effect was mainly observed in younger (6-10 years) children in whom higher lead was associated with slower reaction time.}, } @article {pmid4066719, year = {1985}, author = {Forwood, MR and Neal, RJ and Wilson, BD}, title = {Scaling segmental moments of inertia for individual subjects.}, journal = {Journal of biomechanics}, volume = {18}, number = {10}, pages = {755-761}, doi = {10.1016/0021-9290(85)90050-8}, pmid = {4066719}, issn = {0021-9290}, mesh = {Anthropometry ; Cadaver ; Humans ; *Models, Biological ; *Motion ; }, abstract = {The purpose of this investigation was to validate methods of scaling human segmental moments of inertia for the transverse principal axis. Firstly, two methods of scaling Chandler et al.'s (Pamphlets DOT HS-801 430 and AMRL TR-74-137, Wright Patterson Air Force Base, OH, 1975) mean subject data to estimate the segmental moments of inertia were used. Chandler et al.'s data were scaled using body mass and segment length (formula 1) or body mass and standing height (formula 2). These data were then compared with a procedure of using the cadaver whose anthropometric measurements most closely match those of the subject. The difference between the criterion data (Chandler's subject data) and scaled values were plotted on scatter diagrams with confidence limits of p less than 0.05 at d.f. = 17. For procedure 1, 43% of the scaled values were plotted within the confidence limits using formula (2) (mass and standing height), compared with 26% for formula (1) (mass and segment length). Formula (1) markedly underestimated the tallest and heaviest subjects. In procedure 2, only 16% and 21% of the scaled values, using formula (1) and (2), respectively, fell within the confidence limits. Results suggested that scaling formulae approximate the moment of inertia of body segments with only limited accuracy. However, if scaling was to be adopted then mean moment of inertia data from an appropriate data set, using the formula that incorporates subject mass and standing height, gave results closest to the criterion value.}, } @article {pmid3003369, year = {1985}, author = {Willard, C and Wong, E and Hess, JF and Shen, CK and Chapman, B and Wilson, AC and Schmid, CW}, title = {Comparison of human and chimpanzee zeta 1 globin genes.}, journal = {Journal of molecular evolution}, volume = {22}, number = {4}, pages = {309-315}, pmid = {3003369}, issn = {0022-2844}, support = {AM 29800/AM/NIADDK NIH HHS/United States ; GM 21346/GM/NIGMS NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Animals ; Base Sequence ; Biological Evolution ; Cloning, Molecular ; Codon ; DNA Restriction Enzymes ; *Genes ; Globins/*genetics ; Humans ; Pan troglodytes ; Plasmids ; Species Specificity ; }, abstract = {The DNA base sequences of the entire chimpanzee zeta 1 globin gene and an additional 1 kb of DNA flanking both the human and chimpanzee genes have been determined. Whereas the human zeta 1 gene contains a termination codon in the sixth position, the chimpanzee gene appears to be functional. This finding confirms Proudfoot et al.'s suggestion that the human zeta 1 gene was recently inactivated. Like the corresponding human zeta 1 and zeta 2 genes, the first and second introns of the chimpanzee zeta 1 gene are occupied largely by tandem repeats of short oligonucleotides. These tandem repeats have undergone several rearrangements since the divergence of the human and chimpanzee zeta 1 genes.}, } @article {pmid2997962, year = {1985}, author = {Eimoto, T and Teshima, K and Shirakusa, T and Kikuchi, M}, title = {Ultrastructure of well-differentiated adenocarcinomas of the lung with special reference to bronchioloalveolar carcinoma.}, journal = {Ultrastructural pathology}, volume = {8}, number = {2-3}, pages = {177-190}, doi = {10.3109/01913128509142151}, pmid = {2997962}, issn = {0191-3123}, mesh = {Adenocarcinoma/pathology/*ultrastructure ; Adenocarcinoma, Bronchiolo-Alveolar/pathology/*ultrastructure ; Cytoplasmic Granules/ultrastructure ; Humans ; Lung Neoplasms/pathology/*ultrastructure ; Microscopy, Electron ; }, abstract = {The cytologic phenotypes of 20 well-differentiated pulmonary adenocarcinomas were determined by electron microscopy. On examination of more than 100 cells in each case, the tumors were classified according to the predominant cell types. Nine cases (45%) were of mucous cell type, further divided into 7 cases of bronchial surface epithelial cell type, 1 case of bronchial gland cell type, and 1 case of metaplastic bronchiolar goblet cell type. The remainder included 5 cases (25%) of Clara cell type, 2 cases (10%) of type II cell type, and 4 cases (20%) of mixed cell type. The predominant histologic pattern by light microscopy was "typically" bronchioloalveolar (Manning et al.'s type 1) in the metaplastic goblet cell tumor and papillary in most Clara cell-type tumors, while it was glandular in bronchial surface and bronchial gland cell types, although variable in type II cell or mixed cell type. Therefore, bronchioloalveolar carcinomas, when histologically defined inclusive of papillary tumors, present cytologic phenotypes also related to the bronchioloalveolar epithelium, i.e., metaplastic goblet or Clara or type II cell subtypes, which is in accordance with some previous reports. These tumors could be distinguished from the other (glandular) adenocarcinomas that show primarily bronchial mucous cell differentiation.}, } @article {pmid6520634, year = {1984}, author = {Fukuda, Y and Hsiao, CF and Watanabe, M and Ito, H}, title = {Morphological correlates of physiologically identified Y-, X-, and W-cells in cat retina.}, journal = {Journal of neurophysiology}, volume = {52}, number = {6}, pages = {999-1013}, doi = {10.1152/jn.1984.52.6.999}, pmid = {6520634}, issn = {0022-3077}, mesh = {Animals ; Axons/physiology/ultrastructure ; Cats ; Dendrites/ultrastructure ; Evoked Potentials, Visual ; Neural Conduction ; Photic Stimulation ; Reaction Time/physiology ; Retina/*ultrastructure ; Retinal Ganglion Cells/classification/physiology/*ultrastructure ; }, abstract = {The action spike activities of single ganglion cells were recorded from the nasal retina of the intact eye of anesthetized and immobilized cats. Each ganglion cell was identified as a Y-, X-, or W-cell on the basis of its axonal conduction velocity, its receptive-field properties, and the level of maintained activity. Of about 100 ganglion cells physiologically identified and penetrated with horseradish peroxidase (HRP)-containing glass microelectrodes, 21 cells were subsequently identified in flat-mount preparations of the retinas and processed for detection of HRP. Of a total of nine Y-cells recovered, four had been penetrated at the soma and five at the axon. All had the morphology of the alpha-cell of Boycott and Wässle. Eight X-cells recovered. All had been penetrated at the soma and showed beta-cell morphology. Four W-cells were penetrated at the soma and recovered. Two off-tonic W-cells had small somas (15-16 micron in diam) and sparse dendritic fields, resembling gamma-cells of Boycott and Wässle. They are also similar to "G4" and "G18" of Kolb et al.'s classification. One on-tonic W-cell had somewhat larger soma (18 micron) with a relatively densely branched dendritic field. This corresponds to delta-cell of Boycott and Wässle or to "G15" of Kolb et al. One on-off phasic W-cell had a medium-sized soma (25.3 micron) with a fanlike dendritic expansion characteristic of the "unilateral horizontal broad range cell" of Shkolnik-Yarros or of "G22" of Kolb et al. Alternatively, all these W-cells can be called medium-sized gamma-cells. Among all three classes of ganglion cells, a positive correlation was found between the diameter of the receptive-field center and the dendritic field. Assuming that in the cat retina 1 degree of visual angle = 230 micron, dendritic fields of Y-cells seemed larger than their physiologically determined receptive-field centers. By contrast, the reverse relation was found between these two dimensions in X-cells. Axon diameters ranged from 4.0 to 5.6 micron (mean, 4.5 micron) in Y-cells and from 1.9 to 2.7 micron (mean, 2.2 micron) in X-cells. Three W-cells showed axon diameters of 0.6, 1.1, and 1.8 micron. The axon diameter distributions made from axons labeled by massive injections of HRP into the optic nerve fiber layer showed a pattern of distribution similar to that obtained from physiologically identified Y-, X-, and W-cell axons.}, } @article {pmid6085581, year = {1984}, author = {Yamamoto, K and Yoshikura, H}, title = {Computer programme statistically predicting folding structure of nucleic acids of any length: and examples of calculation.}, journal = {The Japanese journal of experimental medicine}, volume = {54}, number = {6}, pages = {241-247}, pmid = {6085581}, issn = {0021-5031}, mesh = {*Computers ; DNA, Single-Stranded/analysis ; Escherichia coli/analysis ; Models, Biological ; Mosaic Viruses/analysis ; *Nucleic Acid Conformation ; RNA, Bacterial/analysis ; RNA, Ribosomal/analysis ; RNA, Viral/analysis ; *Software ; }, abstract = {We devised a computer programme which calculates "folding probabilities" of single stranded nucleic acids of any length which we want to analyze. The "folding probability" defined by equation (7) (see below) reflects approximate probability of generation of intrastrand annealing in a given region. With this programme, we analyzed Escherichia coli 23S ribosomal RNA, and cucumber mosaic virus RNA segment 3. The calculated data of Escherichia coli 23S ribosomal RNA agreed approximately well with Klein et al.'s electronmicroscopical data [7].}, } @article {pmid6545215, year = {1984}, author = {Minoia, C and Tempini, G and Salvadeo, A and Vitali, MT and Micoli, G}, title = {[Determination of aluminum in the blood: extra-analytical factors].}, journal = {Giornale italiano di medicina del lavoro}, volume = {6}, number = {5-6}, pages = {239-249}, pmid = {6545215}, issn = {0391-9889}, mesh = {Air Pollutants/analysis ; Aluminum/*blood ; Blood Specimen Collection/instrumentation/methods ; Decontamination ; Humans ; Reference Values ; Spectrophotometry, Atomic ; }, abstract = {Values of Al in serum or plasma of normal subjects reported in the literature vary greatly. The wide range reflects the analytical difficulties and large contamination problems. In order to obtain accurate results we report a direct method for determination of Al-S(P) by using flameless atomic absorption spectrophotometry. (ETA-ASS). Special attention was paid to the precautions to be taken in order to minimize external aluminum contamination. Procedures are described to reduce contamination during sample collection, storage and preparation during sample collection, storage and preparation of sample. Reference values for a healthy population were 7.4 + 2.7 (S.D.) micrograms of Al per liter. (n = 78).}, } @article {pmid6493936, year = {1984}, author = {De Pascalis, V and Alberti, ML and Pandolfo, R}, title = {Anxiety, perception, and control of heart rate.}, journal = {Perceptual and motor skills}, volume = {59}, number = {1}, pages = {203-211}, doi = {10.2466/pms.1984.59.1.203}, pmid = {6493936}, issn = {0031-5125}, mesh = {Adult ; Anxiety/*psychology ; *Biofeedback, Psychology ; Cognition ; Electrocardiography ; Electroencephalography ; Female ; *Heart Rate ; Humans ; Male ; *Perception ; Respiration ; }, abstract = {8 women and 8 men took Cattell's IPAT-anxiety questionnaire and later McFarland's test of ability to perceive heart activity. The second test involved subjects' tracking their own heart rates, then they enrolled in an EKG biofeedback session to evaluate ability to increase and decrease heart rate from subjects' resting baselines. At the end of the session each subject completed Blanchard, et al.'s questionnaire to specify the cognitive strategies used for heart-rate control. Heart rate, abdominal respiration rate, respiration amplitude, EEG percent power in theta, alpha, and beta bands were evaluated. Success of heart-rate decrease seemed to depend mainly on activity levels: the subjects who achieved high scores on the activity test decreased heart rate significantly better than did low scorers. The relationship between scores for perception of heart and increases in heart rate was nonsignificant: increased heart-rate seemed to depend on differences in respiration between the rest and periods of increase. The significant, negative correlation between trait anxiety and perceptions of heart activity suggested that anxiety affected subjects' ability to perceive heart rate. The theta EEG power of the right hemisphere was significantly higher in subjects scoring high than for those low in perception of heart activity. During heart-rate increase tasks subjects mainly reported use of 'arousal responses,' similarly during heart-rate decrease tasks they reported use of relaxation responses.}, } @article {pmid6479399, year = {1984}, author = {Sloane, DM and Lee, CF}, title = {Achieving expected parities: a reanalysis of Freedman et al.'s data, 1962-1977.}, journal = {Demography}, volume = {21}, number = {3}, pages = {413-422}, pmid = {6479399}, issn = {0070-3370}, mesh = {Adult ; Child ; Demography ; Educational Status ; Family Characteristics ; *Family Planning Services ; Female ; Humans ; Male ; Marriage ; Michigan ; *Parity ; }, abstract = {A reanalysis of data included in a recent report by Freedman et al. (1980), using methods suggested by Goodman (1978), yields considerably different substantive conclusions than were arrived at by those earlier analysts. These differences clearly point out the hazards of descriptive analysis, especially of sample data which come in the form of contingency tables.}, } @article {pmid6478004, year = {1984}, author = {Furedy, JJ and Heslegrave, RJ}, title = {The relative sensitivities of heart rate and T-wave amplitude to stress: comments on, and some alternative interpretations of, Penzien et al.'s results.}, journal = {Biological psychology}, volume = {19}, number = {1}, pages = {55-61}, doi = {10.1016/0301-0511(84)90010-3}, pmid = {6478004}, issn = {0301-0511}, mesh = {Adaptation, Psychological/physiology ; *Arousal/physiology ; *Electrocardiography ; Heart/innervation ; *Heart Rate ; Humans ; Set, Psychology ; Stress, Psychological/*complications ; Sympathetic Nervous System/physiology ; Vagus Nerve/physiology ; }, abstract = {Although the joint measurement of heart rate (HR) and T-wave amplitude (TWA) in experiments manipulating psychological processes is a sound and fruitful approach, Penzien Hursey, Kotses and Beazel's (1982) interpretation of their results may be questioned on two grounds: (a) Wether the process being manipulated between their groups was really the degree of stress; and (b) whether the degree of threat or aversiveness is really indexed more reliably by HR changes than by changes in TWA. This note questions these two assumptions, and also offers an alternative vagal interpretation of the Penzien et al. (1982) results.}, } @article {pmid12339861, year = {1984}, author = {Drife, J}, title = {Cancer and the pill--comments and criticisms.}, journal = {Journal of obstetrics and gynaecology}, volume = {4}, number = {Suppl 2}, pages = {S94-7}, doi = {10.3109/01443618409074663}, pmid = {12339861}, mesh = {*Breast Neoplasms ; *Contraception ; Contraceptive Agents ; *Contraceptive Agents, Female ; *Contraceptives, Oral ; *Disease ; *Family Planning Services ; *Neoplasms ; }, } @article {pmid6704636, year = {1984}, author = {Cruickshank, PJ}, title = {A stress and arousal mood scale for low vocabulary subjects: a reworking of Mackay et al. (1978).}, journal = {British journal of psychology (London, England : 1953)}, volume = {75 (Pt 1)}, number = {}, pages = {89-94}, doi = {10.1111/j.2044-8295.1984.tb02792.x}, pmid = {6704636}, issn = {0007-1269}, mesh = {Adult ; *Arousal ; Emotions ; Factor Analysis, Statistical ; Female ; Humans ; Male ; Psychometrics ; Stress, Psychological/*diagnosis ; *Vocabulary ; }, abstract = {In an experiment investigating patient mood in an out-patient setting, a Mood Adjective Checklist (Mackay et al., 1978) was administered to 189 patients before and after their consultations, obtaining 366 completed questionnaires. Both the stress and arousal scales in the Mackay et al. checklist contain unequal numbers of positive and negative items, and are thus subject to response bias. When the results were analysed, it was noted that some items in the checklist led to large numbers of question mark responses, and it was discovered that word frequency, used as an estimate of word unfamiliarity, was correlated with the use of the question mark. Furthermore, when question mark responses were treated as missing data, as recommended by Meddis (1972), the factor analytic distinction between stress and arousal disappeared. Next, items giving rise to 15 per cent or more question mark responses were omitted from analysis, and the remaining items factor analysed. The resulting checklist comprised nine high stress items, nine low stress items, four high arousal items and four low arousal items. Mackay et al.'s stress and arousal scales were reconstructed using these items; they were no longer subject to response bias, and were more accessible to low vocabulary subjects.}, } @article {pmid6231326, year = {1984}, author = {Hardy, P and Jouvent, R and Widlöcher, D}, title = {Speech pause time and the retardation rating scale for depression (ERD). Towards a reciprocal validation.}, journal = {Journal of affective disorders}, volume = {6}, number = {1}, pages = {123-127}, doi = {10.1016/0165-0327(84)90014-4}, pmid = {6231326}, issn = {0165-0327}, mesh = {Adult ; Aged ; Depressive Disorder/*psychology/therapy ; Female ; Humans ; Male ; Middle Aged ; Psychiatric Status Rating Scales ; Psychomotor Performance ; *Speech ; Time Factors ; }, abstract = {Sixteen depressed inpatients were studied before the onset of treatment and within 48 h of discharge or of a change in medication. Patients' evaluation included clinical ratings with the Hamilton Depression Rating Scale (HDRS) and the Retardation Rating Scale for Depression (ERD), and measure of Speech Pause Time (SPT). The main results are a confirmation in French-speaking patients of Szabadi et al.'s and Greden et al.'s findings and the strong correlation between SPT changes and ERD score changes. The latter point constitutes a reciprocal validation of SPT and ERD.}, } @article {pmid6477367, year = {1984}, author = {Sobell, MB and Sobell, LC}, title = {The aftermath of heresy: a response to Pendery et al.'s (1982) critique of "Individualized Behavior Therapy for Alcoholics".}, journal = {Behaviour research and therapy}, volume = {22}, number = {4}, pages = {413-440}, doi = {10.1016/0005-7967(84)90084-6}, pmid = {6477367}, issn = {0005-7967}, mesh = {Alcohol Drinking ; Alcoholism/*therapy ; Behavior Therapy/*methods ; Follow-Up Studies ; Humans ; Research Design ; }, } @article {pmid6443129, year = {1984}, author = {Graur, D}, title = {Pattern of nucleotide substitution and the extent of purifying selection in retroviruses.}, journal = {Journal of molecular evolution}, volume = {21}, number = {3}, pages = {221-231}, pmid = {6443129}, issn = {0022-2844}, support = {GM-20293/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Base Sequence ; Biological Evolution ; Codon ; DNA, Viral/*genetics ; *Genes, Viral ; Genetic Variation ; Mutation ; *Phylogeny ; Retroviridae/*genetics ; *Selection, Genetic ; Transcription, Genetic ; }, abstract = {The patterns of point mutation and nucleotide substitution are inferred from nucleotide differences in three coding and two noncoding regions of retroviral genomes. Evidence is presented in favor of the view that the majority of mutations accumulate at the reverse transcription stage. Purifying selection is apparently very weak at the amino acid level, and almost nonexistent between synonymous codons. The pattern of purifying selection obeys the rules previously established in vertebrates [Gojobori T, Li W-H, Graur D (1982) J Mol Evol 18:360-369]; i.e., the magnitude of purifying selection at the amino acid level is negatively correlated with Grantham's [Grantham R (1974) Science 185: 862-864] chemical distances between the amino acids interchanged. We refute Modiano et al.'s [Modiano G, Battistuzzi G, Motulsky AG (1981) Proc Natl Acad Sci USA 78:1110-1114] hypothesis, according to which the pattern of mutation is preadapted to buffer against deleterious mutations. On the contrary, the pattern of mutation reduces the level of conservativeness from that imposed on the amino acid substitution pattern by the structure of the genetic code. The extraordinarily high rate of nucleotide substitution in retroviruses in comparison with that in other organisms is apparently caused by an extremely high rate of mutation coupled with a lack of stringent purifying selection at both the codon and the amino acid levels.}, } @article {pmid6439689, year = {1984}, author = {Minkler, M}, title = {Health promotion in long-term care: a contradiction in terms?.}, journal = {Health education quarterly}, volume = {11}, number = {1}, pages = {77-89}, doi = {10.1177/109019818401100104}, pmid = {6439689}, issn = {0195-8402}, mesh = {Aged ; Health Policy ; *Health Promotion ; Humans ; Life Style ; *Long-Term Care ; Medicaid ; Medicare ; *Nursing Homes ; }, abstract = {While health promotion potentially could play a significant role in improving the health and quality of life of nursing home residents, several major changes must take place if this concept is to hold relevance for the elderly in the long-term care environment. First, interpretations of the concept of health promotion must be broadened to include a focus on macro- as well as micro-level change and on a diversity of target groups including, importantly, policy makers and providers. Second, the "youth bias" inherent in many conventional health promotion efforts must be overcome, so that goals such as decreasing functional dependence in the frail elderly are seen as legitimate and appropriate health promotion foci. Third, viable alternative to nursing home placements must be developed and adequately funded for the many frail elders who would be better served in less intense care environments. And fourth, the dependency producing nature of institutional long-term care must undergo major changes compatible with the goals of promoting individual autonomy and enhancing quality of life. Nutrition, drug use and misuse, mental health, and staff training and retention are four areas examined in a closer look at specific changes needed to create nursing homes amenable to health promotion. Such changes on the institutional level, coupled with a strong national commitment to nursing home reform, are in keeping with Green et al.'s broad definition of health promotion as encompassing a variety of interventions on multiple levels designed to facilitate behavioral changes conducive to health. It is within this larger context that health promotion is seen as holding considerable promise for improving the health and quality of life of the institutionalized elderly.}, } @article {pmid6644529, year = {1983}, author = {Peterson, CA and Knudson, RM}, title = {Anhedonia: a construct validation approach.}, journal = {Journal of personality assessment}, volume = {47}, number = {5}, pages = {539-551}, doi = {10.1207/s15327752jpa4705_16}, pmid = {6644529}, issn = {0022-3891}, mesh = {Adolescent ; Female ; Humans ; Male ; Psychometrics ; Schizotypal Personality Disorder/*psychology ; Statistics as Topic ; }, abstract = {Investigated the convergent and discriminant validity of the anhedonia construct using a multivariable-multimethod design. The 100 subjects displayed a wide range of scores on the Physical Anhedonia Scale, many comparable to the original validation sample of diagnosed schizophrenics. Twenty-one variables were assessed by tests, 16 by subject self-ratings and 16 by peer ratings of the subject. The resultant intercorrelation matrix was analyzed by Golding and Seidman's (1974) two-step principal components procedure. Five of the six second-order components showed good and conceptually meaningful cross method convergence and were named: Pleasureless Introversion, Neurotic Maladjustment, Dependency, Hedonic Deficit #1, Hedonic Deficit #2, and Coarctation. Hedonic Deficits #1 and #2 were shown to be independent from neuroticism, depression, and guilt. The high degree of relationship between anhedonia and introversion, long suggested by clinicians, is confirmed and discussed. Notes on the construct validity of Chapman et al.'s (1976) Physical and Social Anhedonia Scales and Watson et al.'s (1970) MMPI Anhedonia Scale are included.}, } @article {pmid6883010, year = {1983}, author = {Pavlidis, GT}, title = {Erratic sequential eye-movements in dyslexics: comments and reply to Stanley et al.}, journal = {British journal of psychology (London, England : 1953)}, volume = {74}, number = {Pt 2}, pages = {189-193}, doi = {10.1111/j.2044-8295.1983.tb01853.x}, pmid = {6883010}, issn = {0007-1269}, support = {HD-12278-03/HD/NICHD NIH HHS/United States ; }, mesh = {*Attention ; Child ; Dyslexia/diagnosis/*psychology ; *Eye Movements ; Female ; Fixation, Ocular ; Humans ; Male ; *Motion Perception ; }, abstract = {The results of the Pavlidis' dyslexia studies are consistent with the existing literature and have also been recently replicated using the same subject selection criteria, instructions to subjects, experimental procedures, tests and analyses. Stanley et al.'s: (a) subject selection criteria, (b) instructions to subjects, (c) experimental procedures, (d) temporo-spatial characteristics of the sequentially illuminated LEDs and (e) data analysis procedures differ from those used in the Pavlidis' studies and, therefore, also differ their results.}, } @article {pmid6854282, year = {1983}, author = {Ginsburg, N and Riedel, H}, title = {Numerosity estimation with successive presentation: item organization.}, journal = {The Journal of general psychology}, volume = {108}, number = {2d Half}, pages = {169-173}, doi = {10.1080/00221309.1983.9711490}, pmid = {6854282}, issn = {0022-1309}, mesh = {*Discrimination Learning ; *Form Perception ; Humans ; *Pattern Recognition, Visual ; Semantics ; Set, Psychology ; }, abstract = {Previous studies have shown that, with simultaneous presentation, highly organized patterns were overestimated in number compared with random patterns. In an exploratory attempt to apply Das et al.'s model of simultaneous and successive cognitive processes to perception, 62 Ss were asked to estimate the number of items presented visually one at a time. A rate of one item per second was used, and Ss were required to read each item aloud in order to prevent counting. When the stimuli were digits, no difference was found in the estimates for sets of stimuli containing high information vs those containing low information. When words were used as stimuli, estimates were significantly lower for words in sentences than for the same words in random order.}, } @article {pmid6858747, year = {1983}, author = {Reardon, B and Griffing, P}, title = {Factors related to the self-concept of institutionalized, white, male, adolescent drug abusers.}, journal = {Adolescence}, volume = {18}, number = {69}, pages = {29-41}, pmid = {6858747}, issn = {0001-8449}, mesh = {Adolescent ; Antidepressive Agents ; Central Nervous System Depressants ; Hallucinogens ; Humans ; *Institutionalization ; Male ; Parent-Child Relations ; Personality Development ; *Self Concept ; Social Environment ; Substance-Related Disorders/*psychology ; }, abstract = {The main purpose of this research was to examine the relationship between selected drug-related, familial, and demographic variables and the self-concepts of institutionalized, white, male, adolescent drug abusers in a large midwestern city. In addition, the self-concepts of the subjects in the study were compared with the self-concepts of Pulliam et al.'s (1971) non-drug using adolescent sample. The TSCS, a family questionnaire, an index of socioeconomic status, and an interview were used to collect data from 140 subjects. The mean self-concept score of this sample was significantly lower than the mean self-concept score of Pulliam et al.'s sample. Results of a stepwise multiple regression yielded four statistically significant predictors of the subjects' self-concepts: both mother/adolescent relationship and father/adolescent relationship when the adolescent was between age thirteen and his present age; the number of the subject's prior status offenses and the subject's preference for non-depressant drugs. These variables were positively correlated with the subjects' self-concepts. This study demonstrated the importance of differentiating among institutionalized adolescents' self-concepts based on type of drug abused, prior criminal record, and parent/adolescent relationships.}, } @article {pmid6683549, year = {1983}, author = {Aberg, G and af Ekenstam, B and Smith, E}, title = {Pharmacological studies on droxicainide, a new antiarrhythmic agent.}, journal = {Arzneimittel-Forschung}, volume = {33}, number = {5}, pages = {706-710}, pmid = {6683549}, issn = {0004-4172}, mesh = {Anesthesia ; Anesthetics, Local ; Anilides/*pharmacology ; Animals ; *Anti-Arrhythmia Agents ; Cornea/drug effects ; Female ; Guinea Pigs ; Lethal Dose 50 ; Lidocaine/pharmacology ; Male ; Mice ; Rabbits ; Rats ; Rats, Inbred Strains ; Sciatic Nerve/drug effects ; }, abstract = {The antiarrhythmic, local anesthetic and acute local and systemic toxic effects of DL-N-(2-hydroxyethyl)-pipecolinyl-2,6-dimethylanilide (AL-S-1249, droxicainide) and lidocaine were compared in animals. When given intravenously both substances suppressed ouabain-induced arrhythmias in pentobarbital-anesthetized guinea pigs; they were equipotent in this regard and had the same duration of antiarrhythmic action. Both substances produced generally equivalent sensory anesthesia following intradermal administration in the guinea pig and corneal application in the rabbit and block of motor and sensory function when injected near the sciatic nerve in the rat. In these local anesthetic tests and following intradermal administration to rabbits, droxicainide produced less local tissue irritation than lidocaine. When given intravenously to unanesthetized mice and unanesthetized and pentobarbital-anesthetized rats, the LD50's for droxicainide were consistently higher than those for lidocaine. Since droxicainide has antiarrhythmic and local anesthetic properties that are quantitatively similar to lidocaine but local and systemic toxicity that is relatively weaker, its antiarrhythmic and local anesthetic actions merit further study.}, } @article {pmid6671832, year = {1983}, author = {Rybash, JM and Hoyer, WJ and Roodin, PA}, title = {Responses to moral dilemmas involving self versus others.}, journal = {International journal of aging & human development}, volume = {18}, number = {1}, pages = {73-77}, doi = {10.2190/ah2h-dfbx-2r13-07xq}, pmid = {6671832}, issn = {0091-4150}, mesh = {Aged ; Cognition ; *Ego ; Humans ; *Morals ; New York ; }, abstract = {Forty older adults were administered the standard version (i.e. Other-orientation) of Rest et al.'s Defining Issues Test (DIT) and a modified version (i.e., Self-orientation) of the same instrument on two separate occasions. Contrary to the results of previous studies with children and young adults, the self/other manipulation in the present study failed to influence significantly older adults' moral judgments. The role of cognitive/perspective-taking and personal/affective factors in the moral reasoning abilities of the elderly, as well as those of children and young adults, are discussed.}, } @article {pmid6604473, year = {1983}, author = {Pollitt, CC and Bell, K}, title = {Characterisation of the alpha 1-protease inhibitor system in Thoroughbred horse plasma by horizontal two-dimensional (ISO-DALT) electrophoresis. 2. Protease inhibition.}, journal = {Animal blood groups and biochemical genetics}, volume = {14}, number = {2}, pages = {107-118}, doi = {10.1111/j.1365-2052.1983.tb01066.x}, pmid = {6604473}, issn = {0003-3480}, mesh = {Animals ; Blood Proteins/isolation & purification/*pharmacology ; Chymotrypsin/antagonists & inhibitors ; Electrophoresis, Polyacrylamide Gel ; Isoelectric Focusing ; Molecular Weight ; Pancreatic Elastase/antagonists & inhibitors ; Protease Inhibitors/*pharmacology ; Trypsin Inhibitors/pharmacology ; alpha 1-Antitrypsin ; }, abstract = {The protease inhibitory spectra of the eight homozygous Thoroughbred Pi types against trypsin, elastase and chymotrypsin have been determined. The alpha 1-protease inhibitor proteins exhibit three classes of inhibitory specificity towards these enzymes. The Pi types F, I, N and U exhibit class I (trypsin, elastase and chymotrypsin) and class II (trypsin and elastase) types of inhibition and fit Juneja et al.'s (1979) classification of two separate genetic systems Pi 1 and Pi 2 based on differences in the inhibitory spectra against trypsin and chymotrypsin. The remaining four Pi types are exceptions to Juneja et al.'s (1979) classification. Types G, L, S1 and S2 possess class I but not class II proteins. A third class of proteins (class III) which exclusively inhibit chymotrypsin was detected in all eight protease inhibitor types. Type G is well represented by class III proteins because two of the three major proteins of the ISO-DALT pattern inhibit only chymotrypsin and is thus an exception to Juneja et al.'s (1979) classification.}, } @article {pmid6571220, year = {1983}, author = {Nei, M and Tajima, F and Tateno, Y}, title = {Accuracy of estimated phylogenetic trees from molecular data. II. Gene frequency data.}, journal = {Journal of molecular evolution}, volume = {19}, number = {2}, pages = {153-170}, pmid = {6571220}, issn = {0022-2844}, mesh = {Algorithms ; Alleles ; Base Sequence ; Codon ; Computer Simulation ; *Gene Frequency ; *Models, Genetic ; Mutation ; *Phylogeny ; Polymorphism, Genetic ; }, abstract = {The accuracies and efficiencies of three different methods of making phylogenetic trees from gene frequency data were examined by using computer simulation. The methods examined are UPGMA, Farris' (1972) method, and Tateno et al.'s (1982) modified Farris method. In the computer simulation eight species (or populations) were assumed to evolve according to a given model tree, and the evolutionary changes of allele frequencies were followed by using the infinite-allele model. At the end of the simulated evolution five genetic distance measures (Nei's standard and minimum distances, Rogers' distance, Cavalli-Sforza's f theta, and the modified Cavalli-Sforza distance) were computed for all pairs of species, and the distance matrix obtained for each distance measure was used for reconstructing a phylogenetic tree. The phylogenetic tree obtained was then compared with the model tree. The results obtained indicate that in all tree-making methods examined the accuracies of both the topology and branch lengths of a reconstructed tree (rooted tree) are very low when the number of loci used is less than 20 but gradually increase with increasing number of loci. When the expected number of gene substitutions (M) for the shortest branch is 0.1 or more per locus and 30 or more loci are used, the topological error as measured by the distortion index (dT) is not great, but the probability of obtaining the correct topology (P) is less than 0.5 even with 60 loci. When M is as small as 0.004, P is substantially lower. In obtaining a good topology (small dT and high P) UPGMA and the modified Farris method generally show a better performance than the Farris method. The poor performance of the Farris method is observed even when Rogers' distance which obeys the triangle inequality is used. The main reason for this seems to be that the Farris method often gives overestimates of branch lengths. For estimating the expected branch lengths of the true tree UPGMA shows the best performance. For this purpose Nei's standard distance gives a better result than the others because of its linear relationship with the number of gene substitutions. Rogers' or Cavalli-Sforza's distance gives a phylogenetic tree in which the parts near the root are condensed and the other parts are elongated. It is recommended that more than 30 loci, including both polymorphic and monomorphic loci, be used for making phylogenetic trees. The conclusions from this study seem to apply also to data on nucleotide differences obtained by the restriction enzyme techniques.}, } @article {pmid6193745, year = {1983}, author = {Pollitt, CC and Bell, K}, title = {Characterisation of the alpha 1-protease inhibitor system in Thoroughbred horse plasma by horizontal two-dimensional (ISO-DALT) electrophoresis. 1. Protein staining.}, journal = {Animal blood groups and biochemical genetics}, volume = {14}, number = {2}, pages = {83-105}, doi = {10.1111/j.1365-2052.1983.tb01065.x}, pmid = {6193745}, issn = {0003-3480}, mesh = {Animals ; Blood Proteins/*genetics/isolation & purification ; Electrophoresis, Polyacrylamide Gel/instrumentation/methods ; Horses/*blood ; Isoelectric Focusing/instrumentation/methods ; Molecular Weight ; Protease Inhibitors/*genetics ; Staining and Labeling ; alpha 1-Antitrypsin ; }, abstract = {The isoelectric points and the molecular weights of the major components of the eight Thoroughbred protease inhibitor (Pi) types have been determined by polyacrylamide gel isoelectric focusing and polyacrylamide gel pore gradient (ISO-DALT) electrophoresis respectively. The major Pi proteins focus in the range pH 3.74-4.43 and have molecular weights ranging from 55 000-72 000 daltons. Using the ISO-DALT method of electrophoresis, protein maps for the eight Thoroughbred Pi types have been presented for the first time. None of the homozygous Pi types are identical except for the types S1 and S2 which show partial identity. The results do not necessarily support Juneja et al.'s (1979) contention of two closely linked alpha 1 Pi systems based on molecular weight differences. It is suggested that the traditional nomenclature originally proposed by Braend (1970) be maintained to describe the eight Pi alleles in Thoroughbred horse plasma. The ISO-DALT method provides a sensitive technique which is superior to existing techniques for the analysis of the horse Pi system.}, } @article {pmid7166133, year = {1982}, author = {Williams, RJ}, title = {The clinical-correctional interface in the treatment of drug offenders: the evidence from N.S.W. australia.}, journal = {Drug and alcohol dependence}, volume = {10}, number = {2-3}, pages = {211-222}, doi = {10.1016/0376-8716(82)90015-1}, pmid = {7166133}, issn = {0376-8716}, mesh = {Australia ; Counseling ; Humans ; Substance-Related Disorders/*legislation & jurisprudence/rehabilitation/therapy ; }, abstract = {There is a significant overlap between Justice and Health (plus other Community Services) systems in their responsibility for drug offenders. We are met with a paradox however at the interface between correctional and treatment concerns. Though it would be of considerable benefit to mesh these systems each with their own well defined role into closer collaborative effort, it is equally essential that they maintain their respective distances so as to protect the integrity of their individual, possibly conflicting, primary goals (the broader view of Justice in terms of community protection and the narrower focus of Health upon the well-being of the individual). Attempts to organize such an interface emphasising only the requirements of the Correctional System have often led to a counterproductive reaction from Health personnel. Fortunately Aprill et al. [13] have outlined a more harmonious possibility which they distinguish as the Milwaukee Model. It involves clearly defining the special role of a Probation/Parole Worker and integrating it into the day-to-day clinical program so as to specifically fulfill the linkage function between clinic and courts. A contemporaneous development in Sydney (1977-1981) offers some measurement of the Health and Justice personnel's perceptions of a 'diversion' scheme before and after the institution of such a linkage worker. The results are highly supportive of Aprill et al.'s findings.}, } @article {pmid7170199, year = {1982}, author = {De Bernardi, B and Perlino, G and Vitale, V and Stella, G and Cozzutto, C and Magnaguagno, G and Rizzo, A and Comelli, A and Garaventa, A and Barabino, A}, title = {[Ewing's sarcoma. Results of treatment in 16 consecutive cases].}, journal = {La Pediatria medica e chirurgica : Medical and surgical pediatrics}, volume = {4}, number = {3}, pages = {279-286}, pmid = {7170199}, issn = {0391-5387}, mesh = {Adolescent ; Antineoplastic Agents/adverse effects/therapeutic use ; Bone Neoplasms/diagnosis/*therapy ; Child ; Child, Preschool ; Drug Therapy, Combination ; Female ; Humans ; Male ; Radiotherapy Dosage ; Sarcoma, Ewing/diagnosis/*therapy ; }, abstract = {In the period January 1974-August 1981, 16 previously untreated cases of Ewing's Sarcoma have been diagnosed at the Giannina Gaslini Children's Hospital Genova. Eight were male, eight female. Median age at diagnosis was 11 years. Two patients presented with a unique metastatic lesion, in the right lung and in an illiac lymph node, respectively. Fourteen patients have been initially treated with local radiotherapy (dosages ranging form 4,800 to 6,600 rads) in association with antiblastic polichemotherapy utilizing 4 drugs (Adriamycin, Actinomycin D, Vincristine, Cyclophosphamide). The Rosen et al.'s T-2 protocol was adopted, modifying the initial phase in order to give more weight to Adriamycin and reduce the toxic effects related to radio-chemotherapy combination. Two patients bearing a costal primary were immediately treated with a more complex and aggressive chemotherapy (T-6 Protocol), followed by local irradiation (in one case preceded by surgical ablation) and then chemotherapy again (T-2 protocol, second phase) for 10 months. Treatment determined a fast subjective relief in the 13 symptomatic patients. All 16 cases achieved a status of complete remission. Four of them subsequently relapsed: locally in two, in distant sites in the remaining 2. All 4 died 12-27 months form diagnosis. Twelve patients are presently alive without evidence of disease at 3-92 months (median 37 months) following diagnosis. Treatment has caused early and delayed toxicity in all cases. However, the entity of these complications varied considerably from one patient to an other. Age at diagnosis and site of primary tumor were the factors most relevant in this respect.}, } @article {pmid7081306, year = {1982}, author = {Billings, JJ}, title = {Natural family planning methods.}, journal = {American journal of obstetrics and gynecology}, volume = {143}, number = {1}, pages = {114-115}, pmid = {7081306}, issn = {0002-9378}, mesh = {*Family Planning Services ; Female ; Humans ; Male ; *Natural Family Planning Methods ; }, } @article {pmid7073339, year = {1982}, author = {Calguneri, M and Bird, HA and Wright, V}, title = {Changes in joint laxity occurring during pregnancy.}, journal = {Annals of the rheumatic diseases}, volume = {41}, number = {2}, pages = {126-128}, pmid = {7073339}, issn = {0003-4967}, mesh = {Adult ; Female ; Finger Joint/physiology ; Humans ; Joints/*physiology ; Movement ; Parity ; *Pregnancy ; }, abstract = {We have studied changes in peripheral joint laxity occurring during pregnancy in 68 females using both the finger hyperextensometer to quantify laxity at the metacarpophalangeal joint of the index finger and Beighton et al.'s modification of the Carter and Wilkinson scoring system. Although the latter system recorded no change, the more sensitive hyperextensometer demonstrated a significant increase in joint laxity during the last trimester of pregnancy (0.02 greater than p greater than 0.01) over the readings from the same individuals after parturition. When primigravidae and multigravidae were compared, a highly significant increase in laxity was found in women having their second baby over those having their first (0.01 greater than p greater than 0.001), though no further increase in laxity occurred in subsequent pregnancies.}, } @article {pmid7108690, year = {1982}, author = {Lavigne, JV and Daruna, JH}, title = {A comment on Epstein et al.'s "comparison of family-based behavior modification and nutrition education for childhood obesity".}, journal = {Journal of pediatric psychology}, volume = {7}, number = {1}, pages = {95-98}, doi = {10.1093/jpepsy/7.1.95}, pmid = {7108690}, issn = {0146-8693}, mesh = {*Behavior Therapy ; Child ; Child Nutritional Physiological Phenomena ; Humans ; Nutritional Sciences/*education ; Obesity/*therapy ; Patient Education as Topic ; Research Design/standards ; }, } @article {pmid7168457, year = {1982}, author = {Galbraith, RC and Olsen, SF and Duerden, DS and Harris, WL}, title = {The differentiation hypothesis: distinguishing between perceiving and memorizing.}, journal = {The American journal of psychology}, volume = {95}, number = {4}, pages = {655-667}, pmid = {7168457}, issn = {0002-9556}, mesh = {Attention ; Child ; Child Development ; Child, Preschool ; Female ; *Form Perception ; Humans ; Male ; *Memory ; *Mental Recall ; *Pattern Recognition, Visual ; Retention, Psychology ; }, abstract = {The differentiation hypothesis states that perceiving and memorizing are functionally undifferentiated for young children (preschoolers). With age, additional strategies are implemented under intentional recall conditions, thus providing greater recall than under incidental conditions. Appel and colleagues presented initial evidence in 1972 that appeared to support the predicted Age X Recall Instruction (incidental, intentional) interaction of the differentiation hypothesis. Subsequent research in children's memory, however, has failed to replicate the critical features of the Appel et al. data. A closer look at Appel et al.'s procedures revealed a methodological flaw present in both their Experiments 1 and 2--the variable of instructional condition was manipulated within subjects. In addition, an inspection of their reported Age X Instruction interaction revealed a larger quadratic than linear component. The difference between incidental and intentional recall first increased and then decreased with age. Correcting for these errors of method and analysis, the present experiment found no support for the differentiation hypothesis. Recall did increase with age, but the increase was not differential with respect to incidental or intentional recall instructions.}, } @article {pmid7162597, year = {1982}, author = {Liederman, J and Coryell, J}, title = {The origin of left hand preference: pathological and non-pathological influences.}, journal = {Neuropsychologia}, volume = {20}, number = {6}, pages = {721-725}, doi = {10.1016/0028-3932(82)90074-4}, pmid = {7162597}, issn = {0028-3932}, mesh = {Birth Injuries/psychology ; Brain Damage, Chronic/*psychology ; *Choice Behavior ; Female ; Fetal Distress/psychology ; *Functional Laterality ; Humans ; Infant ; Infant, Newborn ; Male ; Obstetric Labor Complications/psychology ; Posture ; Pregnancy ; Pregnancy Complications/psychology ; }, abstract = {Models of the origin of left hand preference were tested with prospective data. Infants with and without a history of perinatal complications, matched for age, sex and parental handedness, were filmed at 6 weeks of age. Children with a history of perinatal complications lacked the rightward headturning bias of those children without a history of perinatal trauma. Children with a history of perinatal complications were also deviant with reference to the duration of a postural reflex and its degree of lateralization. Perinatal complications may delay the establishment of volitional hand use as well as increase the probability of left-handedness. The data were interpreted as supporting SATZ's (Cortex 8, 121-135, 1972) rather than BAKAN et al.'s (Neuropsychologia 11, 363-366, 1973) model of "pathological" left-handedness.}, } @article {pmid7161732, year = {1982}, author = {Greene, SM and O'Mahony, PD and Rungasamy, P}, title = {Levels of measured hopelessness in physically-ill patients.}, journal = {Journal of psychosomatic research}, volume = {26}, number = {6}, pages = {591-593}, doi = {10.1016/0022-3999(82)90074-5}, pmid = {7161732}, issn = {0022-3999}, mesh = {Adaptation, Psychological ; Adolescent ; Adult ; Aged ; Depression/*psychology ; Female ; Humans ; Male ; Middle Aged ; *Motivation ; Psychological Tests ; Psychometrics ; *Sick Role ; }, abstract = {Beck et al.'s Hopelessness Scale was administered to a group of 60 general hospital patients suffering from a variety of physical disorders. The group consisted of 30 chronically- and 30 acutely-ill patients. The mean Hopelessness Scale score for the whole group was 3.75 (SD 2.7). This mean score did not differ significantly from the mean Hopelessness Scale score obtained from a large sample from the general population. However it was significantly lower than the mean score of 40 clinically-depressed psychiatric hospital patients. No significant differences were found between the levels of measured hopelessness of the chronically ill and acutely ill.}, } @article {pmid7100986, year = {1982}, author = {Honig-Parnass, T}, title = {The effects of latent social needs on physician utilization by immigrants: a replication study.}, journal = {Social science & medicine (1982)}, volume = {16}, number = {5}, pages = {505-514}, doi = {10.1016/0277-9536(82)90304-5}, pmid = {7100986}, issn = {0277-9536}, mesh = {Adaptation, Psychological ; Adult ; Catharsis ; *Emigration and Immigration ; Health Services/*statistics & numerical data ; Humans ; Israel ; Middle Aged ; Models, Theoretical ; *Social Adjustment ; Social Class ; Socioeconomic Factors ; *Sociology, Medical ; }, abstract = {The research reported in the present paper is a replication of Shuval et al.'s study of the effects of latent social needs of new immigrants on their utilization of health care services. By restoring to path analysis, the replication undertook to explore two questions: (1) Is the need for catharsis (i.e. for emotional support) found by Shuval et al. to affect utilization directly (i.e. not via illness) indeed characteristic only for the first years of stay in the host country. (2) Isn't it rather the differential access to social resources, ad determined by social class and age, which at present explains the need-utilization relationship? The findings show that even though the need still persists among the one-time immigrants, it is a quite poor predictor of all other attributes found to affect physician utilization: viz. the emotional and physical illness and the tendency to define oneself as ill. With the passage of time the former immigrants seem to have abandoned the previously customary mode of gratifying the need for catharsis by turning to the health services. Hence, even the respondents with a keen experience of that need tended to refrain from turning to physicians in the absence of 'concrete' symptoms. At the same time, the lower classes and the elderly, without experiencing the need for catharsis, turned to have higher rates of physician visits, simply by virtue of being relatively more ill. In conclusion, a plea is made for the improvement of the design flaws common for the type of causal inquiry into the need-utilization relationship, which this study represents.}, } @article {pmid7055503, year = {1982}, author = {Stark-Adamec, C and Adamec, RE and Graham, JM and Bruun-Meyer, SE and Perrin, RG and Pollock, D and Livingston, KE}, title = {Analysis of facial displays and verbal report to assess subjective state in the non-invasive detection of limbic system activation by procaine hydrochloride.}, journal = {Behavioural brain research}, volume = {4}, number = {1}, pages = {77-94}, doi = {10.1016/0166-4328(82)90166-8}, pmid = {7055503}, issn = {0166-4328}, mesh = {Diazepam ; Electric Stimulation ; *Emotions ; *Facial Expression ; Female ; Hallucinations ; Heart Rate ; Humans ; Limbic System/*physiology ; Male ; *Procaine ; Verbal Behavior ; }, abstract = {The problem of scalp EEG as a measure of cortical or subcortical activity is particularly relevant to complex partial seizures as the abnormal discharging is frequently limbic in origin [14, 30]. Livingston [38] has suggested that administration of intravenous procaine as a limbic activator and cortical suppressor would be of utility in diagnosing limbic involvement in complex partial seizures. While there is considerable evidence derived from experimental animal models that procaine hydrochloride is a limbic system activator that acts preferentially on subcortical epileptic foci at lower doses than on less active epileptic foci or non-epileptic tissue [2, 4], it was necessary to demonstrate that procaine activates the human limbic system. The non-invasive approach taken in the present study was to compare the published effects of direct electrical stimulation of the human limbic system [31] to the behavioural and subjects effects of intravenous procaine administration. The areas in which we obtained the most robust procaine effects (hallucinations, emotions and alimentary sensations) were also Halgren et al.'s [31] most repeatable effects. The correspondence between electrical stimulation effects and procaine administration effects was striking - with verbal report by patients matching exactly in many instances. Furthermore, analysis of facial displays proved useful in providing access to subjects state fluctuations which would otherwise have gone undetected. The data provide strong evidence that procaine hydrochloride can be used as a human limbic system activator. Future research will investigate the clinical and diagnostic significance of differential response to procaine.}, } @article {pmid6280039, year = {1982}, author = {Georgescu, L and Drăgan, M and Teodorescu, M and Diosi, P and Petraşcu-Stefanovici, O and Raica, M}, title = {Polymorphism of nuclear inclusions in carcinoma of the cervix uteri.}, journal = {Morphologie et embryologie}, volume = {28}, number = {1}, pages = {31-34}, pmid = {6280039}, issn = {0377-5038}, mesh = {Adult ; Aged ; Antibodies/analysis ; BK Virus/immunology ; Carcinoma, Squamous Cell/*ultrastructure ; Cell Nucleus/*ultrastructure ; Cytomegalovirus/immunology ; Cytoplasm/ultrastructure ; Female ; Humans ; Inclusion Bodies/*ultrastructure ; Inclusion Bodies, Viral/ultrastructure ; Middle Aged ; Simplexvirus/immunology ; Uterine Cervical Neoplasms/immunology/*ultrastructure ; }, abstract = {Frequency, polymorphism and ultrastructural characteristics of the nuclear inclusion bodies encountered in cancers of the uterine cervix are reported and briefly discussed. The nuclear inclusions are grouped in three distinct types: a) nuclear bodies (comprising type I and II inclusions according to Bouteille et al.'s classification), b) inclusion of cytoplasmic origin, and c) particles of chromatic material. The ultrastructural aspects of the chromatic particles suggest an early structuration of viral chromatin into core material. There appears to be a direct relation between the frequency of chromatic particles and raised antiherpetic antibodies in the patient's sera.}, } @article {pmid10314545, year = {1981}, author = {Toffler, BL}, title = {Occupational role development: the changing determinants of outcomes for the individual.}, journal = {Administrative science quarterly}, volume = {26}, number = {3}, pages = {396-418}, pmid = {10314545}, issn = {0001-8392}, mesh = {Analysis of Variance ; Humans ; *Job Satisfaction ; Models, Theoretical ; Physician Assistants/*psychology ; *Role ; United States ; }, abstract = {This research examined the development of an occupational role from one month before the role incumbent's graduation from training to five months into the first job. Kahn et al.'s (1964) theory of ""expectation-generated role stress" provided a conceptual framework for the development of a causal model of role development. A national sample of 181 physicians' assistants (PAs) and their supervising physicians reported by questionnaire on actual and expected PA task performance and participation in decision making at three points during the period of interest. Task data were used to derive three measures of objective role ambiguity and conflict. In addition, PAs provided data on perceived role ambiguity and conflict and attitudes about work, A path analytic technique was applied to the model to examine changes over time. Results suggest that, during the first months of employment, the role occupant passes through different stages of development, during which the determinants of outcomes change. This notion of changing causal structure was supported by the identification of four casual patterns of outcomes, the changing strength of prediction models, and the changing effects of discrepancies between pre-job expectation and on-the-job reality. Role-development stages are discussed in terms of rational and emotional processes, and implications for theory, research, and practice are proposed.}, } @article {pmid7300349, year = {1981}, author = {Rodgers, NT and Kaufman, DG}, title = {The measurement of cytosolic estrogen receptors in human endometrial tissue and organ cultures.}, journal = {Journal of steroid biochemistry}, volume = {14}, number = {8}, pages = {801-806}, doi = {10.1016/0022-4731(81)90018-2}, pmid = {7300349}, issn = {0022-4731}, support = {K04-CA00431/CA/NCI NIH HHS/United States ; N01-CP75956/CP/NCI NIH HHS/United States ; }, mesh = {Centrifugation, Density Gradient ; Chromatography, Gel ; Cytosol/metabolism ; Endometrium/*metabolism ; Estradiol/metabolism ; Female ; Hot Temperature ; Humans ; Menstruation ; Organ Culture Techniques ; Receptors, Estrogen/*metabolism ; }, } @article {pmid12265917, year = {1981}, author = {}, title = {Study raises question of spermicide safety.}, journal = {Contraceptive technology update}, volume = {2}, number = {5}, pages = {57-61}, pmid = {12265917}, issn = {0274-726X}, mesh = {*Congenital Abnormalities ; Congenital, Hereditary, and Neonatal Diseases and Abnormalities ; *Contraception ; Contraceptive Agents ; *Contraceptive Agents, Female ; Disease ; Family Planning Services ; *Reproductive Control Agents ; *Spermatocidal Agents ; }, } @article {pmid7229204, year = {1981}, author = {Lass, NJ}, title = {A reply to Cohen et al.'s "Weighty voices and shaky evidence: a critique" [J. Acoust. Soc. Am. 68, 1884--1886 (1980)].}, journal = {The Journal of the Acoustical Society of America}, volume = {69}, number = {4}, pages = {1204-1206}, doi = {10.1121/1.385702}, pmid = {7229204}, issn = {0001-4966}, mesh = {*Body Height ; *Body Weight ; Female ; Humans ; Male ; *Speech Perception ; }, } @article {pmid15178537, year = {1980}, author = {Johnson, P}, title = {The relative weightings of visual and nonvisual coding in a simple motor learning task.}, journal = {Journal of motor behavior}, volume = {12}, number = {4}, pages = {281-291}, doi = {10.1080/00222895.1980.10735227}, pmid = {15178537}, issn = {0022-2895}, abstract = {A linear positioning task was used to examine the effects of visual and nonvisual inputs on motor learning. The experiment had three factors with two levels of each namely: sensory modality (visual-nonvisual), transfer at recall (changed-unchanged), size of movement (25.4 cm, 50.8 com). Three dependent variable were used: absolute error (AE), constant error (CE), and variable error (VE). The results suggest that visual dominance causes disruption of recall in the visual, changed conditions. No disruption of recall was found for the nonvisual condition other than in terms of CE with respect to movement sizes. The results are taken to follow Posner et al.'s (1976) theory of visual dominance, but some account of the spatial qualities of visual and kinesthetic information is needed.}, } @article {pmid7430265, year = {1980}, author = {Benos, DJ}, title = {Intracellular analysis of sodium, potassium, and chloride in mouse erythrocytes.}, journal = {Journal of cellular physiology}, volume = {105}, number = {1}, pages = {185-187}, doi = {10.1002/jcp.1041050120}, pmid = {7430265}, issn = {0021-9541}, mesh = {Animals ; Chlorides/*blood ; Erythrocytes/*analysis ; Mice ; Potassium/*blood ; Sodium/*blood ; }, abstract = {Recently, Cameron et al. ('79) published measurements of intracellular solute amounts (expressed as mmoles per kilogram dry cell solids) obtained by energy dispersive electron probe microanalysis in different rodent tissues. In this communication, I wish to compare Cameron et al.'s ('79) erythrocyte values of Na, K, and Cl with those I have made using more conventional techniques of elemental analysis. This comparison is necessitated by Cameron et al.'s ('79) observation of extremely high intracellular sodium levels. If their findings are accurate, the possibility of a polymorphism with respect to intracellular Na levels therefore presents itself. If a polymorphism between different inbred strains of mice exists, and if, as in ruminants, this trait has a genetic basis, an examination of the genetic aspects of the control, differentiation, and the ultimate expression of the ion transport mechanisms responsible would undoubtedly provide insight into the molecular basis as well as the adaptive dynamics of transport systems in general.}, } @article {pmid7193191, year = {1980}, author = {Morley, JS and Wei, ET}, title = {Hexahydro derivative of (D-Met2, Pro-NH2(5)]-enkephalin gives rise to physical dependence.}, journal = {International journal of peptide and protein research}, volume = {16}, number = {4}, pages = {254-258}, doi = {10.1111/j.1399-3011.1980.tb02585.x}, pmid = {7193191}, issn = {0367-8377}, support = {DA-00091/DA/NIDA NIH HHS/United States ; }, mesh = {Animals ; Behavior, Animal/drug effects ; Biological Assay ; Endorphins/*chemical synthesis ; Enkephalins/*chemical synthesis/pharmacology ; Guinea Pigs ; Humans ; Ileum/drug effects ; Indicators and Reagents ; Methods ; Mice ; Rats ; Substance-Related Disorders ; }, abstract = {Filippi et al. (1979) have claimed that substitution of cyclohexylalanine for phenylalanine in leucine-enkephalin and its L-Ser3 derivative resulted in synthetic analogs which were non-addicting. We have examined the hexahydro derivative of [D-Met2, Pro-NH2(5)]-enkephalin, a potent analgesic agent, to determine if dependence liability can be separated from short-term opiate actions after hydrogenation of the phenylalanine residue. In contrast to Filippi et al.'s observations, we found that the hexahydro derivative of [D-Met2, Pro-NH2(5)]-enkephalin gives rise to physical dependence and that its short-term potencies generally paralleled its long-term ability to produce physical dependence.}, } @article {pmid7429032, year = {1980}, author = {Beattie, RC and Culibrk, J}, title = {Effects of a competing message on the speech comfortable loudness level for two instructional sets.}, journal = {Ear and hearing}, volume = {1}, number = {5}, pages = {242-248}, doi = {10.1097/00003446-198009000-00003}, pmid = {7429032}, issn = {0196-0202}, mesh = {Acoustic Stimulation ; Adolescent ; Adult ; Female ; Humans ; *Loudness Perception ; *Research Design ; *Speech Perception ; }, abstract = {The effects of a competing message on the speech comfortable loudness level (CLL) was compared for two instructional sets in 2 conditions of quiet and in the presence of a four-talker babble competing message. Kopra and Blosser's (24) instructions were selected to sample the middle of the CLL range, whereas Lucker et al.'s (27) instructions sampled the upper limit of the CLL range. Two groups of 12 normal-hearing subjects were tested using a method of adjustment. The results indicated no significant differences between the initial and final CLL's in quiet. However, data for each instructional set showed that the CLL's obtained with Lucker et al.'s phraseology (97.8 dB SPL) was significantly higher than with Kopra and Blosser's instructions (75.2 dB SPL). The four-talker babble served to raise the CLL, although less effect was observed on the upper limit of the CLL range than for the middle portion of this range. The clinical implications of these findings are discussed.}, } @article {pmid7446321, year = {1980}, author = {Ek, N and Braend, M}, title = {Quantitative comparisons of acidic prealbumin (PR) phenotypes in horses.}, journal = {Acta veterinaria Scandinavica}, volume = {21}, number = {3}, pages = {380-388}, pmid = {7446321}, issn = {0044-605X}, mesh = {Animals ; Female ; Horses/*genetics ; Male ; Phenotype ; Prealbumin/*genetics ; Serum Albumin/*genetics ; Sex Factors ; }, abstract = {Comparisons of Pr protein amounts in horse sera have been performed using Mancini et al.’s (1965) immunodiffusion technique. Relative values against a chosen standard of 100 % were determined for a total of 435 horses. There was considerable variation between horses, the highest Pr value being 125 % and the lowest 50 % of the standard. In animals of the same Pr phenotype the mean Pr values were significantly higher (P < 0.001) in foals than in mares. In Norwegian Trotter horses the Pr value of Pr NN animals was significantly higher than that of Pr SS phenotypes, whereas the mean Pr values of Pr SS was significantly higher than that of Pr UU Warmblood Trotter horses, the Pr value of Pr SS being 90 % and the Pr-UU 80 % of that of Pr NN. No difference between sexes with regard to Pr values was found.}, } @article {pmid6784457, year = {1980}, author = {Ek, N}, title = {Concentration of serum prealbumin (PR) protein in sick horses and its correlation to blood leucocyte count and albumin content in serum.}, journal = {Acta veterinaria Scandinavica}, volume = {21}, number = {4}, pages = {482-497}, pmid = {6784457}, issn = {0044-605X}, mesh = {Animals ; Horse Diseases/*blood ; Horses ; Immunodiffusion/veterinary ; Leukocyte Count/veterinary ; Prealbumin/*analysis ; Serum Albumin/*analysis ; }, abstract = {Studies of Pr protein concentrations in sera of sick horses were carried out using Mancini et al.’s (1965) immunodiffusion technique. Relative values against a chosen standard of 100 % were determined for a total of 102 horses. Horses with acute infections had Pr protein values significantly above the normal. The highest individual Pr protein value recorded in this group was 202. Horses suffering from acute laminitis and malignant tumours also had increased Pr protein values. There was a positive correlation between the Pr protein value and the blood leucocyte count and a negative correlation between the Pr protein value and the albumin content in serum.}, } @article {pmid536304, year = {1979}, author = {Slutsky, AS and Drazen, JM}, title = {Estimating central and peripheral respiratory resistance: an alternative analysis.}, journal = {Journal of applied physiology: respiratory, environmental and exercise physiology}, volume = {47}, number = {6}, pages = {1325-1331}, doi = {10.1152/jappl.1979.47.6.1325}, pmid = {536304}, issn = {0161-7567}, mesh = {*Airway Resistance ; Animals ; Dogs ; Electricity ; Mathematics ; Methods ; Models, Biological ; Regression Analysis ; }, abstract = {Pimmel et al (J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 45: 375--380, 1978) recently presented an analysis of the frequency dependence of respiratory resistance (Rrs) based on a simple electrical analog of the respiratory system that allows estimation of the central (Rc) and peripheral (Rp) components of Rrs. The method by which they determine these parameters from the experimental data is based on a number of unproven assumptions. Using the same electrical analog, we present an analysis that allows calculation of these parameters, as well as the corner frequency of the network (f1), without need for similar assumptions. Our technique is based on fitting the resistances (RTh) measured over a range of frequencies (f) to the exact solution of the network given by RTh = Rc + Rpf1(2)/f2 + f1(2)). Using the transformation X = 1/(f2 + f1(2), the equation becomes a linear relationship between RTh and X allowing the resistances to be determined by linear regression. Reanalysis of Pimmel et al.'s data demonstrated that the assumptions of a constant f1, and the equivalence of RTh at 0 Hz to RTh at 1 Hz in invalid under certain conditions. Thus, if one is to use the electrical analog to partition Rrs into its central and peripheral components, one should use the analytic approach suggested here that does not rely on these assumptions.}, } @article {pmid546454, year = {1979}, author = {Donchin, E and Heffley, EF}, title = {The independence of the P300 and the CNV reviewed: a reply to Wastell.}, journal = {Biological psychology}, volume = {9}, number = {3}, pages = {177-188}, doi = {10.1016/0301-0511(79)90038-3}, pmid = {546454}, issn = {0301-0511}, mesh = {*Contingent Negative Variation ; *Electrophysiology ; *Factor Analysis, Statistical ; Humans ; }, abstract = {The relationship of P300 to the CNV was investigated by Donchin, Tueting, Ritter, Kutas and Heffley (1975) who concluded that these two components of the event-related brain potential (ERP) are independent. Wastell (1979) questioned the validity of the data analysis procedures and of the experimental design used by Donchin et al. In this report we examine Wastell's criticisms and find them to be unfounded. In support of this conclusion we note the differences between principal component analysis and factor analysis. We clarify points about Donchin et al.'s experimental design, and we review evidence for the independence of the P300 and the CNV that has accumulated since 1975.}, } @article {pmid546453, year = {1979}, author = {Wastell, DG}, title = {On the independence of P300 and the CNV: a short critique of the principal components analysis of Donchin et al. (1975).}, journal = {Biological psychology}, volume = {9}, number = {3}, pages = {171-188}, doi = {10.1016/0301-0511(79)90037-1}, pmid = {546453}, issn = {0301-0511}, mesh = {*Contingent Negative Variation ; *Electrophysiology ; *Factor Analysis, Statistical ; Humans ; }, abstract = {Donchin, Tueting, Ritter, Kutas and Heffley (1975) present evidence from a principal components analysis (PCA) that the CNV and P300 are independent. This short critique points out a number of erros in their PCA and presents a reworking of their analysis. A number of further aspects of Donchin et al.'s paper are also discussed. The general value of this contribution in drawing the attention of EP researchers to potential sources of error in the application of factor analysis is emphasized.}, } @article {pmid499590, year = {1979}, author = {Rubinfeld, Y and Maor, Y and Simon, D and Modai, D}, title = {A progressive rise in serum copper levels in women taking oral contraceptives: a potential hazard?.}, journal = {Fertility and sterility}, volume = {32}, number = {5}, pages = {599-601}, doi = {10.1016/s0015-0282(16)44366-9}, pmid = {499590}, issn = {0015-0282}, mesh = {Adolescent ; Adult ; Contraceptives, Oral/*pharmacology ; Copper/*blood ; Female ; Humans ; Menstruation ; Time Factors ; }, } @article {pmid514770, year = {1979}, author = {Franco, JN and Croft, DB}, title = {Personality and environmental variables associated with dental anxiety.}, journal = {Perceptual and motor skills}, volume = {49}, number = {2}, pages = {529-530}, doi = {10.2466/pms.1979.49.2.529}, pmid = {514770}, issn = {0031-5125}, mesh = {Age Factors ; Anxiety/*diagnosis ; Dental Care/*psychology ; Humans ; *Personality ; *Social Environment ; Socioeconomic Factors ; }, abstract = {94 adult dental patients' anxiety was assessed. Scores on Spielberger, et al.'s inventory showed attractiveness of the waiting room, age, and Edwards' Harmavoidance were significantly related to anxiety.}, } @article {pmid431862, year = {1979}, author = {Minella, M and Rognoni, G and Fortina, A and Brustia, A and Rossi, P and Aquili, C}, title = {[Automatic method for the evaluation of the extent of myocardial infarct from the serum of CPK curve].}, journal = {Minerva medica}, volume = {70}, number = {4}, pages = {325-331}, pmid = {431862}, issn = {0026-4806}, mesh = {Adult ; Aged ; Automation ; Clinical Enzyme Tests ; Creatine Kinase/*blood ; Female ; Humans ; Isoenzymes/blood ; Male ; Middle Aged ; Myocardial Infarction/blood/*diagnosis ; Prognosis ; Spectrophotometry ; }, abstract = {An off-line system for calculating the extent of infarct from serial serum CPK determinations based on Sobel et al.'s compartmental model is presented. Results in 40 patients with acute infarct in a coronary unit showed that the index of infarct extent had an appreciable prognostic significance. Employment of the MB isoenzyme in the calculation could, it is felt improve the sensitivity of the method.}, } @article {pmid521238, year = {1979}, author = {Vaughan, M and Krawiecka, M}, title = {Sensitivity to change in symptoms of new scales for rating chronic psychotic patients.}, journal = {International pharmacopsychiatry}, volume = {14}, number = {3}, pages = {121-126}, doi = {10.1159/000468370}, pmid = {521238}, issn = {0020-8272}, mesh = {Adult ; Chronic Disease ; Evaluation Studies as Topic ; Female ; Humans ; Male ; *Psychiatric Status Rating Scales ; Psychotic Disorders/*psychology ; }, abstract = {The sensitivity of Krawiecka, Goldberg and Vaughan's scales for rating chronic psychotic patients was established by testing them under conditions comparable to those of a controlled cross-over trial. 34 chronic schizophrenics were assessed on the scales at the beginning, after 6 weeks on one form of medication and after the same period on another drug. Significant changes in ratings of symptom severity of anxiety, hallucination delusions and incoherence were observed in patients who were sympomatic at the outset. Further, patterns of intercorrelations were found to be stable over time. It was concluded that Krawiecka et al.'s scales may be sensitive to change in symptoms in chronic psychotics and that given their known reliability, they may be viable research tools.}, } @article {pmid725234, year = {1978}, author = {Hueso, P and Rocha, M}, title = {[Comparative study of six methods for lymphocyte isolation from several mammalian sources and determination of their carbohydrate composition (author's transl)].}, journal = {Revista espanola de fisiologia}, volume = {34}, number = {3}, pages = {339-344}, pmid = {725234}, issn = {0034-9402}, mesh = {Animals ; Carbohydrates/*analysis ; Cattle ; Cell Separation/*methods ; Hexosamines/analysis ; Hexoses/analysis ; Histology, Comparative ; Horses ; Lymphocytes/*analysis ; Sialic Acids/analysis ; Swine ; }, abstract = {The present paper deals with a comparative study on six methods for isolation of peripheral blood lymphocytes from various mammalian sources: Bos taurus L. (adult cow), Equus caballus L. (adult horse), Equus asinus L. (adult and young donkeys) and Sus scropha L. (adult pig). The following systems were used: a) Filtration through sand columns (a modification of Blaszczyszyn's method); b) Sodium metrizoate and "Ficoll 400" c) "Lymphoprep"; d) "Urovison" and dextran T150 (a modification of GILI et al.'s method); e) "Urografin" and dextran T150; f) "Ficoll-Paque". The final preparation of lymphocytes obtained by "Urovison" and dextran T150 (d = 1.081) procedure was free from platelets and erythrocytes; lymphocytes degree of purity was found to be 98%. The sialic acids, hexoses and hexosamines contents were determined.}, } @article {pmid361964, year = {1978}, author = {Hillman, H and Deutsch, K}, title = {Area changes in slices of rat brain during preparation for histology or electron microscopy.}, journal = {Journal of microscopy}, volume = {114}, number = {1}, pages = {77-84}, doi = {10.1111/j.1365-2818.1978.tb00117.x}, pmid = {361964}, issn = {0022-2720}, mesh = {Brain/*anatomy & histology ; Freezing ; Glycerol ; *Histological Techniques ; Microscopy, Electron ; }, abstract = {Cerebral slices cut from rat brain, either 2-3 mm or 0.27 mm thick, were used to study the effect of embedding and freezing. Paraffin wax sections 6 micrometer thick were mounted and stained with haematoxylin and eosin or Marsland et al.'s (1954) silver stain, and their areas were examined at each step. Embedding in paraffin wax of slices 2-3 mm thick, or in Epon of slices 0.27 mm thick, caused a diminution of their areas by 20-30%. Staining of paraffin wax sections did not alter their areas. Glycerol alone at 15% concentration had no effect on the areas, but at 30% concentration they were diminished by approximately 20%. Diminution of the areas of glycerol treated slices 0.27 mm thick also occurred when they were transferred to liquid N2 or to isopentane, but the areas increased after glycerol was replaced by Freon 12. It was concluded that embedding or freezing cerebral slices caused changes in their areas, but that staining of sections after they had been embedded, sectioned and mounted did not.}, } @article {pmid679707, year = {1978}, author = {Reynolds, DM and Jeeves, MA}, title = {A developmental study of hemisphere specialization for alphabetical stimuli.}, journal = {Cortex; a journal devoted to the study of the nervous system and behavior}, volume = {14}, number = {2}, pages = {259-267}, doi = {10.1016/s0010-9452(78)80052-5}, pmid = {679707}, issn = {0010-9452}, mesh = {Adolescent ; Adult ; Child ; *Child Development ; *Dominance, Cerebral ; Female ; Functional Laterality ; Humans ; Pattern Recognition, Visual ; Reaction Time ; *Reading ; Visual Fields ; }, abstract = {Three groups of normal female subjects (7 and 8 years of age, 13 and 14 years of age, and young adults) were tested on a choice reaction time task using a tachistoscopic presentation of single letters to either hemisphere. The two older groups of subjects were found to exhibit a significant right visual field (left hemisphere) superiority in reaction time to letters, but the 7 and 8 year old children did not show a hemisphere asymmetry. These reaction time results for the two older groups are consistent with Rizzolatti et al.'s (1971) finding of a right visual field superiority in reaction time to letters in male adults. The analyses of error rates for visual field differences were not significant for the children or the adolescents. In this study, in contrast to Rizzolatti et al.'s result with male adults, the female adults produced a significant visual field difference in error rate.}, } @article {pmid660664, year = {1978}, author = {Czelusniak, J and Goodman, M and Moore, GW}, title = {On investigating the statistical properties of the populous path algorithm by computer simulation. Counterconclusions to those of Tateno and Nei.}, journal = {Journal of molecular evolution}, volume = {11}, number = {1}, pages = {75-85}, pmid = {660664}, issn = {0022-2844}, mesh = {*Biological Evolution ; Computers ; Mutation ; *Nucleotides ; Proteins ; Statistics as Topic ; }, abstract = {Goodman et al.'s (1974) populous path algorithm for estimating hidden mutational change in protein evolution is designed to be used as an adjunct to the maximum parsimony method. When the algorithm is so used, the augmented maximum parsimony distances, far from being overestimates, are underestimates of the actual number of nucleotide substitutions which occur in Tateno and Nei's (1978) computer simulation by the Poisson process model, even when the simulation is carried out at two and a half times the sequence density. Although underestimates, our evidence shows that they are nevertheless more accurate than estimates obtained by a Poisson correction. In the maximum parsimony reconstruction, there is a bias towards overrepresenting the number of shared nucleotide identities between adjacent ancestral and descendant nodal sequences with the bias being stronger in those portions of the evolutionary tree sparser in sequence data. Because of this particular property of maximum parsimony reconstructed sequences, the conclusions of Tateno and Nei concerning the statistical properties of the populous path algorithm are invalid. We conclude that estimates of protein evolutionary rates by the maximum parsimony--populous path approach will become more accurate rather than less as larger numbers of closely related species are included in the analysis.}, } @article {pmid660663, year = {1978}, author = {Tateno, Y and Nei, M}, title = {Goodman et al.'s method for augmenting the number of nucleotide substitutions.}, journal = {Journal of molecular evolution}, volume = {11}, number = {1}, pages = {67-73}, pmid = {660663}, issn = {0022-2844}, mesh = {*Biological Evolution ; Computers ; Mutation ; *Nucleotides ; Statistics as Topic ; }, abstract = {Statistical properties of Goodman et al.'s (1974) method of compensating for undetected nucleotide substitutions in evolution are investigated by using computer simulation. It is found that the method tends to overcompensate when the stochastic error of the number of nucleotide substitutions is large. Furthermore, the estimate of the number of nucleotide substitutions obtained by this method has a large variance. However, in order to see whether this method gives overcompensation when applied together with the maximum parsimony method, a much larger scale of simulation seems to be necessary.}, } @article {pmid911980, year = {1977}, author = {Wilkinson, DA and Morowitz, HJ and Prestegard, JH}, title = {Hydration of phosphatidylocholine. Adsorption isotherm and proton nuclear magnetic resonance studies.}, journal = {Biophysical journal}, volume = {20}, number = {2}, pages = {169-179}, pmid = {911980}, issn = {0006-3495}, mesh = {Magnetic Resonance Spectroscopy ; Mathematics ; Myristic Acids ; *Phosphatidylcholines ; Structure-Activity Relationship ; Thermodynamics ; Water ; }, abstract = {Adsorption-desorption isotherms were obtained for water binding by 1,2-dimyristoylphosphatidylcholine in the temperature range 15 degrees-35 degrees C. The isotherms were analyzed by Brunauer et al.'s (BET) theory and also a polarization theory, the latter being more successful in fitting the data. There was some evidence for a change in the surface field of the lipid bilayer around 25 degrees C. Proton T1 and T2 measurements were used to obtain a log-normal molecular correlation time distribution for water protons in these systems. This distribution was compared with the isotherm data to effect a description of several classes of water molecules.}, } @article {pmid886432, year = {1977}, author = {Wilmoth, GH and McFarland, SG}, title = {A comparison of four measures of moral reasoning.}, journal = {Journal of personality assessment}, volume = {41}, number = {4}, pages = {396-401}, doi = {10.1207/s15327752jpa4104_11}, pmid = {886432}, issn = {0022-3891}, mesh = {Adult ; Cognition ; Female ; Humans ; *Judgment ; Male ; Middle Aged ; *Morals ; Personality ; *Psychological Tests ; }, abstract = {Kohlberg's Moral Judgment Scale, Gilligan et al.'s Sexual Moral Judgment Scale, Maitland and Goldman's Objective Moral Judgment Scale, and Hogan's Maturity of Moral Judgment Scale, were examined for reliability and inter-scale relationships. All measures except the Objective Moral Judgment Scale had good reliabilities. The obtained relations between the Moral Judgment Scale and the Sexual Moral Judgment Scale replicated previous research. The Objective Moral Judgment Scale was not found to validly assess the Kohlberg stages. The Maturity of Moral Judgment Scale scores were strongly related to the subjects's classification on the Kohlberg stages, and the scale appears to offer a reliable, quickly scored, and valid index of mature thought, although the scale's continuous scores do not permit clear stage classification.}, } @article {pmid965556, year = {1976}, author = {Cicchetti, DV and Ryan, ER}, title = {A reply to Beutler et al.'s study: some sources of variance in accurate empathy ratings.}, journal = {Journal of consulting and clinical psychology}, volume = {44}, number = {5}, pages = {858-861}, doi = {10.1037//0022-006x.44.5.858}, pmid = {965556}, issn = {0022-006X}, mesh = {*Empathy ; Evaluation Studies as Topic ; Humans ; Professional-Patient Relations ; *Psychotherapy ; *Research Design ; }, } @article {pmid58802, year = {1976}, author = {Lamothe, F and Laurecin-Piché, J and Côté, J and Guévin, R and Viallet, A and Richer, G}, title = {Detection of surface and core antigens of hepatitis B virus in the liver of 164 human subjects. A study by immunoperoxidase and orcein staining.}, journal = {Gastroenterology}, volume = {71}, number = {1}, pages = {102-108}, pmid = {58802}, issn = {0016-5085}, mesh = {Hepatitis B Antigens/*analysis ; Humans ; Immunologic Techniques ; Liver/*immunology/pathology ; Liver Diseases/*immunology/pathology ; Oxazines ; Peroxidases ; Staining and Labeling ; }, abstract = {The surface (HBsAg) and core (HBcAg) antigens of hepatitis B virus (HBV) have been searched by optic microscopy in the liver specimens from patients hospitalized for various conditions and from 38 HGsAg chronic carriers. The study was done blindly using Shikata et al.'s orcein staining on fixed and frozen material and direct immunoperoxidase on frozen material with antisera specific for surface (anti-HBs) and core (anti-HBc) antigens of HBV. No liver staining could be found in the 98 HBsAg seronegative patients. Among the 28 HBsAg seropositive patients, only 3 showed positive staining: 1 patient with acute viral hepatitis showed nuclear staining with anti-HBc; 2 patients with postnecrotic cirrhosis showed cytoplasmic staining with anti-HBs and/or orcein, and one of them also showed nuclear staining with anti-HBc. In contrast, among the 38 chronic carriers, 25 showed positive cytoplasmic staining with anti-HBs and/or orcein, while one of them (with chronic aggressive hepatitis) also showed nuclear staining with anti-HBc. Anti-HBs and orcein staining are equally sensitive and specific for the detection of HBsAg in hepatocytes; discrepant results can be attributed to sampling error of distribution of HBsAg in small liver fragments.}, } @article {pmid1044044, year = {1976}, author = {Tetreault, AI}, title = {Selected factors associated with professional attitude of baccalaureate nursing students.}, journal = {Nursing research}, volume = {25}, number = {1}, pages = {49-53}, pmid = {1044044}, issn = {0029-6562}, mesh = {Adult ; *Attitude of Health Personnel ; Behavior ; Birth Order ; Career Choice ; *Education, Nursing, Baccalaureate ; Educational Status ; Female ; Humans ; *Nursing ; Parents ; Psychological Tests ; Semantic Differential ; *Students, Nursing ; Teaching ; }, abstract = {To examine the association between professional attitude and selected situational and demographic factors of baccalaureate nursing students, 157 female students from an upper division major who had not had other college or nursing education answered a questionnaire which incorporated Osgood et al.'s Semantic Differential Test, Hogan's Professional Attitude Test, and an adaptation of the Dawson et al. instructor-leader behaviors. Eight hypotheses were tested. Professional attitude was found to be highest for students 24 to 26 years of age, who saw nursing as highly positive and highly active, had most formal and informal nursing experience, and perceived teachers as taking strong positions on their beliefs and relating to them with high consideration throughout their program and with low structuring when they were seniors. Professional attitude of students was not associated significantly with potency attributed to nursing, career choice, parents' level of education, or placement in sibling group.}, } @article {pmid1219925, year = {1975}, author = {Lara, PF and Valle, LB and da Rosa, JC and de Lucia, R and Oliveira-Filho, RM and Camara, SA}, title = {Normal values of thyroxine and triiodo-thyronine retention in the rat. Valores normais de tiroxina e retenção de triiodo-tironina em ratos.}, journal = {Revista brasileira de pesquisas medicas e biologicas}, volume = {8}, number = {5-6}, pages = {363-367}, pmid = {1219925}, issn = {0034-7310}, mesh = {Animals ; Female ; Male ; Rats/*blood ; Thyroxine/*blood ; }, abstract = {The authors report the results from Murphy and Pattee's method 9, 10 1964, 1966 for T4 and those from Hamolsky et al.'s method 5 1957 for percent retention of T3 as applied to the normal rat serum. For that purpose, 32 adult Wistar rats, of both sexes, kept at the laboratory environment and fed with usual diet were used. Blood samples were taken after noon directly from the heart, without anesthesia. The analysis showed a T4 value of 4.20 +/- 0.92 mug/100 ml of serum (both sexes). The percentuals for mean T3 retention values were found to be 87.46 +/- 6.59% (male) and 81.78 +/- 5.22% (female). No statistically significant correlation could be drawn between the body weights and the hormonal findings.}, } @article {pmid1161368, year = {1975}, author = {Visintainer, MA and Wolfer, JA}, title = {Psychological preparation for surgery pediatric patients: the effects on children's and parents' stress responses and adjustment.}, journal = {Pediatrics}, volume = {56}, number = {2}, pages = {187-202}, pmid = {1161368}, issn = {0031-4005}, mesh = {Adaptation, Psychological ; Adolescent ; Age Factors ; Child ; Child Behavior ; *Child, Hospitalized ; Child, Preschool ; Cooperative Behavior ; Female ; Humans ; Male ; Manifest Anxiety Scale ; *Parents ; *Pediatric Nursing ; Postoperative Care ; *Preoperative Care ; Professional-Family Relations ; Psychology, Child ; *Stress, Psychological ; }, abstract = {This clinical experiment tested variations of psychological preparation and supportive care designed to increase the adjustment of children (and their parents) hospitalized for elective surgery. Eighty-four children, aged 3 to 12, admitted for tonsillectomies were randomly assigned to one of three treatment conditions or to a control group: (1) a combination of systematic preparation, rehearsal, and supportive care conducted prior to each stressful procedure; (2) a single-session preparation conducted after admission, and (3) consistent supportive care given by one nurse at the same points as in the first condition, but including no systematic preparation or rehearsal. The children's hospital adjustment was measured by blind ratings of behavioral upset and cooperation during the blood test, medication injection, transport to surgery, induction, and postoperative fluid intake and by recovery room medications and pulse rates and time to first voiding. Post-hospital adjustment was assessed with Vernon et al.'s Post Hospital Behavior Inventory. Parent outcome measures included self-ratings for anxiety and satisfaction with information and care. As hypothesized, the results demonstrated that children who received condition one showed significantly less upset and more cooperation and their parents reported significantly greater satisfaction and less anxiety than did children or parents in the other groups. Younger children were significantly more upset and less cooperative than older children.}, } @article {pmid1137554, year = {1975}, author = {Huston, JP}, title = {Reinterpretation of Crow et al.'s "Electrophysiological correlates of cortical spreading depression".}, journal = {Behavioral biology}, volume = {14}, number = {3}, pages = {403-404}, doi = {10.1016/s0091-6773(75)90595-7}, pmid = {1137554}, issn = {0091-6773}, mesh = {Animals ; *Cortical Spreading Depression ; Electrodes ; *Electrophysiology ; Methods ; Rats ; }, } @article {pmid1141131, year = {1975}, author = {Watanabe, S and Frank, R}, title = {Lung volumes, mechanics, and single-breath diffusing capacity in anesthetized cats.}, journal = {Journal of applied physiology}, volume = {38}, number = {6}, pages = {1148-1152}, doi = {10.1152/jappl.1975.38.6.1148}, pmid = {1141131}, issn = {0021-8987}, mesh = {Anesthesia ; Animals ; Body Weight ; Carbon Monoxide ; Cats/*physiology ; Female ; Lung/anatomy & histology ; Lung Compliance ; Lung Volume Measurements ; Male ; Organ Size ; *Pulmonary Diffusing Capacity ; Pulmonary Ventilation ; *Respiration ; Species Specificity ; }, abstract = {We measured lung weight, lung volumes, pulmonary mechanics, and carbon monoxide transfer (DLCO, single-breath method) in healthy cats (3.3 +/- 0.4 kg) that were anesthetized, paralyzed, and mechanically ventilated through a tracheal cannula. Compared with Stahl's predicted values which were based on regression analyses of data collected from several species, our cats had larger and more compliant lungs in relation to body weight, higher DLCO per unit body weight, and similar DLCO/TLC (size independent constant). Compared with Robinson et al.'s values derived entirely from studies on dogs, our cats had significantly smaller lung volumes and DLCO per unit body weight, DLCO/TLC and similar ratios of CL/FRC. Several factors appear to contribute to the functional variations among mammalian species: differences in the relation of lung to body weight, differences in the relation of chest wall compliance to lung compliance, and differences in the fundamental structure and design of the respiratory systems. Differences in methodology are acknowledged to be an additional factor.}, } @article {pmid1056326, year = {1975}, author = {Manly, BF}, title = {A second look at some data on a cline.}, journal = {Heredity}, volume = {34}, number = {3}, pages = {423-426}, doi = {10.1038/hdy.1975.52}, pmid = {1056326}, issn = {0018-067X}, mesh = {Animals ; Female ; *Genetics, Population ; Longevity ; Male ; Moths ; *Phenotype ; Probability ; }, abstract = {The release-recapture data given in table 1 of Kettlewell et al.'s (1969) paper on a cline in the frequencies of the typica and edda morphs of the moth. Amathes glareosa have been re-analysed. Estimates of daily survival probabilities have been calculated and these have been "explained" in terms of differences between localities of release and the morph involved. The conclusions of Kettlewell et al. (1969) with regard to the survival of the moths have not been confirmed.}, } @article {pmid236533, year = {1975}, author = {Berger, M and Gribetz, D and Korelitz, BI}, title = {Growth retardation in children with ulcerative colitis: the effect of medical and surgical therapy.}, journal = {Pediatrics}, volume = {55}, number = {4}, pages = {459-467}, pmid = {236533}, issn = {0031-4005}, mesh = {Adolescent ; Body Weight ; Child ; Child, Preschool ; Colectomy ; Colitis, Ulcerative/*complications/drug therapy/surgery ; Female ; Growth ; Growth Disorders/*etiology ; Humans ; Hydrocortisone/therapeutic use ; Ileostomy ; Infant ; Male ; Prednisone/therapeutic use ; Sulfasalazine/therapeutic use ; }, abstract = {The growth of 37 children with ulcerative colitis have been analyzed. While conventional growth charts showed only percentile changes in height, height data plotted on Tanner et al.'s growth charts showed increases and decreases in growth velocity. Growth retardation is a prominent complication of ulcerative colitis with onset on bowel symptoms. Both ulcerative colitis and "high-dose" steroid therapy (greater than 12 mg/sq m/day of cortisol) can hinder growth but in some instances there is a growth spurt after high-dose steroid therapy. "Low-dose" steroid therapy does not retard growth. Colectomy is more effective than high-dose steroid therapy in reversing the growth retardation caused by ulcerative colitis and is of greatest value if not delayed too long. Growth following subtotal colectomy with ileorectal anastomosis (Aylett procedure) is not likely to be as much as that after subtotal colectomy with ileostomy. Growth retardation is infrequently the only indication for surgical intervention but ileostomy and colectomy are appropriate for this complication of ulcertive colitis in itself when not improved by adequate medical treatment.}, } @article {pmid1207433, year = {1975}, author = {Miller, DI and Morrison, WE}, title = {Prediction of segmental parameters using the Hanavan human body model.}, journal = {Medicine and science in sports}, volume = {7}, number = {3}, pages = {207-212}, pmid = {1207433}, issn = {0025-7990}, mesh = {Anthropometry ; *Body Composition ; Body Weight ; Computers ; Humans ; Male ; *Models, Biological ; Specific Gravity ; Sports Medicine ; }, abstract = {The Hanavan mathematical model of the human body was updated utilizing Clauser et al.'s multi-step weight distribution regression equations. The influence of these equations upon the predicted segment weights, specific gravities and principal moments of inertia of 30 adult male athletes was compared to that of Barter's regression equations employed in the original model. Both methods resulted in descrepancies between actual body weight and the predicted sum of the segment weights with Barter's equations consistently underestimating total body weight by an average of 2.03% and Clauser et al.'s overestimating it by 4.59%. Proportional distribution of the discrepancies produced corrected segment weights which were used in the Hanavan model. Clauser et al.'s equations predicted heavier trunks and thighs, and lighter heads, upper arms, forearms and hands with these differences being reflected in the specific gravities and principal moments of intertia. While it was not possible to establish the definite superiority of Clauser et al.'s equations in the prediction of body segment parameters, it is suggested from inferential evidence that they be used in subsequent biomechanical investigations of adult male athletes which involve the Hanavan model. It is also recommended that continued efforts be made to refine the Hanavan human body model.}, } @article {pmid5437572, year = {1970}, author = {Kaufman, GE and Miller, MW}, title = {A statistical evaluation of Sparrow et al.'s relationship of Do to chromosome volume.}, journal = {Radiation research}, volume = {42}, number = {1}, pages = {181-187}, pmid = {5437572}, issn = {0033-7587}, mesh = {Chromosomes/*radiation effects ; *Radiation Genetics ; Statistics as Topic ; }, } @article {pmid13034291, year = {1952}, author = {NANDI, DN}, title = {Studies in the schizophrenic metabolism: a study of liver function by Quick et al.'s (1938) benzoic-acid test.}, journal = {The Indian journal of medical research}, volume = {40}, number = {3}, pages = {303-311}, pmid = {13034291}, issn = {0971-5916}, mesh = {*Benzoic Acid ; *Liver ; *Liver Function Tests ; Proteins/*metabolism ; Schizophrenia/*physiology ; }, } @article {pmid40824591, year = {2025}, author = {Kong, M and Yu, W and Guo, J and Wang, Z and Fan, D}, title = {Two-step Mendelian randomization reveals a lipid-driven protective effect of type 2 diabetes on ALS.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {}, number = {}, pages = {}, pmid = {40824591}, issn = {1590-3478}, support = {81873784//National Natural Science Foundation of China/ ; 82071426//National Natural Science Foundation of China/ ; BYSYDL2019002//Clinical Cohort Construction Program of Peking University Third Hospital/ ; BYSYZD2021004//key Program of Peking University Third Hospital/ ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder with few therapeutic options. Observational data suggest that type 2 diabetes mellitus (T2DM) might protect against ALS, yet the mechanisms are unclear. Clarifying whether glucose or lipid metabolism underpins this protective effect could guide targeted interventions.

OBJECTIVE: This study aims to investigate if T2DM reduces ALS risk through glycemic or lipid pathways using a two-step Mendelian Randomization (MR) approach.

METHODS: Summary-level genetic data were sourced from FinnGen (n = 440,735), MAGIC (n = 200,622), UK Biobank (n = 115,078), and Project MinE (n = 138,086). Two-sample MR assessed T2DM's causal effect on ALS, followed by multivariable MR adjusting for glycemic traits to identify metabolic pathways. A two-step MR analyzed significant blood metabolites contributing to the T2DM-ALS relationship. Sensitivity analyses confirmed the robustness of these findings.

RESULTS: T2DM exhibited a protective causal association with ALS (inverse variance weighting OR = 0.956, 95% CI 0.916-0.997, p = 0.037). Glycemic traits did not mediate this protection; instead, lipid metabolism played a role. Specifically, a 1 SD reduction in LDL diameter was linked to a 16.7% decrease in ALS risk, accounting for 24.4% of T2DM's protective effect. Similarly, a 1 SD decrease in total esterified cholesterol (TEC) reduced ALS risk by about 13.2%, contributing to 13.3% of T2DM's overall protective impact. No evidence of horizontal pleiotropy was observed.

CONCLUSION: T2DM's protective influence on ALS primarily involves lipid rather than glucose pathways, highlighting TEC and LDL particle diameter as crucial mediators. Targeting lipid metabolism may offer new therapeutic strategies to reduce ALS risk or progression, potentially leading to focused nutritional interventions and biomarker development.}, } @article {pmid40824324, year = {2025}, author = {Jagaraj, CJ and Mehta, P and Hunter, J and Atkin, JD}, title = {A Slower-Progressing TDP-43 rNLS8 Mouse Model for ALS: Implications for Preclinical and Mechanistic Studies.}, journal = {Neuromolecular medicine}, volume = {27}, number = {1}, pages = {59}, pmid = {40824324}, issn = {1559-1174}, support = {51909/00//Fight MND Drug Development grant/ ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterised by motor neuron degeneration, muscle weakness, paralysis, and eventual death, with TAR DNA-binding protein 43 (TDP-43) pathology observed in almost all cases. Mouse models based on TDP-43 are thus essential for studying ALS and developing therapeutic approaches. The TDP-43 rNLS8 mouse model expresses a human TDP-43 transgene with a mutated nuclear localization sequence (hTDP-43 ΔNLS), but this is normally suppressed by the presence of doxycycline (Dox). Disease is initiated by removal of Dox, which replicates key ALS features, including TDP-43 pathology, neuromuscular junction denervation, motor neuron loss, and reduced survival. However, this model has a rapid disease progression which limits its use for extended preclinical studies and investigation of early disease mechanisms. To overcome these limitations, we explored whether maintaining low Dox concentrations in the diet (10-20 mg/kg) could slow disease progression. Our findings demonstrate that this approach significantly reduced hTDP-43 ΔNLS expression (up to 4.8-fold), which delayed disease onset by four weeks. Disease progression, assessed by rotarod performance, grip strength, and neurological scores, was extended from six to 15 weeks, with a threefold increase in survival. Despite slower progression, at the end stage, mice displayed similar levels of neuroinflammation, motor neuron loss, as Dox off mice. These findings highlight slower-progressing TDP-43 rNLS8 mice as a robust model for preclinical and early disease mechanism studies.}, } @article {pmid40822241, year = {2025}, author = {Tan, X and Gao, N}, title = {The emerging role of cellular senescence in amyotrophic lateral sclerosis.}, journal = {Frontiers in neuroscience}, volume = {19}, number = {}, pages = {1599492}, pmid = {40822241}, issn = {1662-4548}, abstract = {Cellular senescence is a state of permanent cell cycle arrest and is considered a key contributor to aging and age-related diseases, including amyotrophic lateral sclerosis (ALS). The physiological processes of aging lead to a variety of molecular and cellular phenotypes, and evidence of overlap between ALS and aging-related biomarkers suggests that cell type-specific senescence may be a critical factor in ALS. Senescent microglial cells, astrocytes, and neurons have been detected in ALS patients and animal models. However, while accumulating evidence suggests a potential link between cellular senescence and ALS, this connection remains not yet conclusively established. Importantly, how senescent cells may contribute to the neuropathophysiology of ALS remains largely unknown. Additionally, the growing popularity of anti-aging therapies has highlighted the potential of senescent cell clearance as a promising strategy for treating age-related diseases, including ALS. This review provides an overview of cellular senescence, discusses recent advances in understanding how senescence in different cell types influences ALS pathogenesis, and explores the potential role of anti-senescence therapies in ALS treatment.}, } @article {pmid40822158, year = {2025}, author = {Cao, G and Shi, X and Wang, X and Yang, L and Wang, P and Yuan, Y and Tan, H}, title = {Combined Single-Bundle Anterior Cruciate Ligament and Anterolateral Structure Reconstruction Through a Modified Single Femoral Tunnel.}, journal = {Arthroscopy techniques}, volume = {14}, number = {7}, pages = {103614}, pmid = {40822158}, issn = {2212-6287}, abstract = {Anterior cruciate ligament (ACL) injuries are among the most common sports injuries, and ACL reconstruction is an important treatment method. Residual rotational stability following isolated ACL reconstruction is the main reason for graft rupture and unsatisfactory results. Many researchers have shown that combined ACL and anterolateral structure (ALS) reconstruction could decrease rotational instability and graft rupture rate, as well as improve satisfaction. Various methods have been described to reconstruct the ACL and ALS jointly. However, previous methods still have disadvantages, such as undesirable tunnel convergence, complex maneuver, and insufficient graft filling in the tibial tunnel. Therefore, we present our technique for reconstruction of the ACL and ALS through a modified single femoral tunnel. We have obtained promising clinical outcomes with this technique.}, } @article {pmid40821656, year = {2025}, author = {Sanghai, N and Tranmer, GK}, title = {Use of Proteomics to Explore Biomarkers of Amyotrophic Lateral Sclerosis (ALS): Proof of Principle from Humanized SOD1 Mouse to Human ALS.}, journal = {ACS pharmacology & translational science}, volume = {8}, number = {8}, pages = {2415-2430}, pmid = {40821656}, issn = {2575-9108}, abstract = {Amyotrophic lateral sclerosis (ALS) is a rare motor neurodegenerative disease affecting multiple cellular proteins during the progression of the disease. ALS was first discovered by Charcot in 1869, and since then, scientists have been unable to identify a singular cause of the disease. Further, there are no effective treatments available to cure ALS. The benchmark discovery of humanized preclinical SOD1 mouse models, which recapitulates the clinical and pathological phenotypes of human ALS, gives hope to medicinal chemists and neuroscientists around the globe that a suitable drug-like molecule can be discovered and translated into human beings as a means to slow down the progression of the disease. However, little success has been achieved until now in terms of finding an effective treatment for heterogenic and incurable ALS. One area marked for improvement is the use of semiquantitative, antibody-based targeted Western blotting (WB) experiments, which lack the power to analyze multiple cellular events within the entire dysregulated proteomic system. With the inconsistency of WB experiments, unexpected cellular pathways go undiscovered, and hence, loss of translation with no target engagement is seen from preclinical to human clinical ALS. Recent advancements in discovery-based quantitative proteomics have many advantages over WB. These innovative techniques could help solve the inherent problem in WB and their inability to discover multiple altered proteins with the added capability of longitudinal analysis in preclinical SOD1 models, further validating the findings in human ALS. Herein, we applied a holistic approach to summarize various reports on the use of proteomics in ALS from the published literature, and importantly, we found that using a discovery-based proteomics approach in SOD1 preclinical ALS models has revealed a more diverse and global picture of pathological proteins that affect multiple pathways during different stages of disease progression. Furthermore, we found that the proteomic profiling of the humanized SOD1 mouse model provided a proof of principle for translating the diverse pathological biomarker proteins identified in clinical human ALS cases. Moreover, we believe that advancements in the proteomics approach toward ALS biomarkers could bridge the gap between preclinical and clinical studies, enabling scientists worldwide to discover novel biomarkers and treatments that modify the progression of ALS.}, } @article {pmid40821619, year = {2023}, author = {Kao, TH and Perry, BJ}, title = {The Current State and Future Directions of Swallowing Care in Amyotrophic Lateral Sclerosis.}, journal = {Current physical medicine and rehabilitation reports}, volume = {11}, number = {2}, pages = {199-211}, pmid = {40821619}, issn = {2167-4833}, abstract = {PURPOSE OF REVIEW: Difficulty swallowing (dysphagia) is of great concern to patients with ALS as its complications can increase mortality and reduce the quality of life. This review aims to provide an overview of the recent developments and the current state of assessment, treatment, and management of dysphagia in ALS.

RECENT FINDINGS: The optimal timing of assessment, treatment, and management of dysphagia may be early in the ALS disease process, even before the dysphagia occurs. There is wide heterogeneity in SLP practice patterns for the management of dysphagia.

SUMMARY: Dysphagia is common and debilitating; however, for various reasons, there is no clear consensus on how best to manage dysphagia in this population. Future work centered around predicting swallowing decline and improving interventions aimed at prolonging swallowing function in the early stages of the disease process may promote improved dysphagia care.}, } @article {pmid40819564, year = {2025}, author = {Ramírez-Núñez, O and Rico-Ríos, S and Torres, P and Ayala, V and Fernàndez-Bernal, A and Ceron-Codorniu, M and Andrés-Benito, P and Vinyals, A and Maqsood, S and Ferrer, I and Pamplona, R and Portero-Otin, M}, title = {Nuclear pore complex dysfunction drives TDP-43 pathology in ALS.}, journal = {Redox biology}, volume = {86}, number = {}, pages = {103824}, doi = {10.1016/j.redox.2025.103824}, pmid = {40819564}, issn = {2213-2317}, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive motor neuron degeneration and pathological aggregation of TDP-43. While protein misfolding and impaired autophagy are established features, accumulating evidence highlights the nuclear pore complex (NPC)as a vulnerable, redox-sensitive hub in ALS pathogenesis. Here, we show that selective loss of NPC components, particularly the scaffold proteins NUP107 and NUP93, and FG-repeat-containing components-is a consistent finding across ALS postmortem spinal cord, SOD1^G93A and TDP-43 mutant mouse models, and human cell systems.CRISPR-mediated depletion of NUP107 in human cells triggers hallmark features of ALS pathology, including cytoplasmic TDP-43 mislocalization, increased phosphorylation, and autophagy dysfunction. Conversely, TDP-43 knockdown perturbs NPC composition, suggesting a reciprocal regulatory loop. Crucially, we demonstrate that oxidative stress exacerbated NPC subunit mislocalization and enhanced TDP-43 aggregation. Using oxime blotting and DNPH assays, we show that FG-repeat subunits of NPC were direct targets of redox-driven carbonylation, indicating that oxidative modifications compromise NPC integrity thuspotentially affecting nucleocytoplasmic transport. Our findings established NPC dysfunction as a redox-sensitive driver of TDP-43 pathology in ALS and highlight nucleocytoplasmic transport as a promising therapeutic axis. The susceptibility of long-lived NPC proteins to oxidative damage provides a mechanistic link between redox stress, proteostasis collapse, and neurodegeneration.}, } @article {pmid40819256, year = {2025}, author = {Nagel, DA and Charlton, P and Azar, R and Koenig, L and Burns, K and Kean, T}, title = {RADAR-ES: A Methodological Framework for Conducting Environmental Scans in Health Services Delivery Research.}, journal = {Journal of primary care & community health}, volume = {16}, number = {}, pages = {21501319251363783}, doi = {10.1177/21501319251363783}, pmid = {40819256}, issn = {2150-1327}, abstract = {AIM: To propose a methodological framework for conceptualizing, planning, and implementing an environmental scan (ES) in health services delivery research (HSDR).

BACKGROUND: An ES is a methodological approach employed to examine a range of practices, policies, issues, programs, technologies, trends, and opportunities from a variety of data sources to inform program or policy development. Despite the wide use of ESs in health care to inform decision-making, a lack of methodological guidance exists to support researchers in planning and conducting an ES in HSDR.

METHODS: Adapting McMeekin et al's process for developing methodological frameworks, we identified literature that described approaches to planning and conducting ESs in addition to exemplar articles that featured ESs in HSDR. We integrated original research findings and synthesized data from all sources to generate an evidence-informed methodological framework.

RESULTS: We developed RADAR-ES that consists of 5 phases and is informed by 4 guiding principles: (1) Recognizing the Issue; (2) Assessing Factors for ES; (3) Developing an ES Protocol; (4) Acquiring and Analyzing the Data; and (5) Reporting the Results.

CONCLUSION: RADAR-ES will provide comprehensive guidance for researchers and health services stakeholders who plan and conduct ESs in HSDR.}, } @article {pmid40818674, year = {2025}, author = {Tian, H and Hang, S and Huang, N and Yu, H and Chen, C and Ge, C}, title = {Strain-level variation in diacetyl production by Lactiplantibacillus plantarum reveals genetic drivers of flavor in fermented dairy.}, journal = {Journal of dairy science}, volume = {}, number = {}, pages = {}, doi = {10.3168/jds.2025-27128}, pmid = {40818674}, issn = {1525-3198}, abstract = {Strain-level diversity in aroma formation remains undercharacterized in Lactiplantibacillus plantarum, a key adjunct culture in dairy fermentation. We screened 351 isolates from traditional Chinese fermented foods for diacetyl production and identified wide phenotypic variation, with strain WJ108 producing 26.85 ± 0.72 mg/kg, which is more than double that of known high producers. Selected strains representing high, medium, and low diacetyl yields were analyzed using GC-MS, revealing ketone enrichment in high producers and aldehyde and alcohol accumulation in low producers. Electronic nose profiling and principal component analysis confirmed distinct volatile signatures across groups. Quantitative PCR (qPCR) analysis showed that α-acetolactate synthase (ALS) and NADH oxidase (NOX) were upregulated in high producers, whereas lactate dehydrogenase, alcohol dehydrogenase, and pyruvate formate lyase were dominant in low producers. Correlation analysis confirmed that W1C, W3C, and W5C electronic nose sensors were highly responsive to ketones. Integrated GC-MS and qPCR data further revealed that NOX and ALS genes positively regulate diacetyl and acetoin biosynthesis in L. plantarum. These results establish a genetic and metabolic basis for aroma diversity in L. plantarum and support the precision selection of strains with enhanced flavor-forming potential for dairy applications.}, } @article {pmid40818509, year = {2025}, author = {Wang, Y and Lin, J and Qu, Y and Ding, Y and Ye, Z and Zhu, Z and Chen, W and Chen, Z and Sun, H and Hu, F and Chen, C and Fang, L and Li, R and Zhang, B and Wang, N and Fu, Y and Chen, W and Zhang, Q and , }, title = {Biomarker profile of a Chinese ALS cohort: A comprehensive clinical-biomarkers-imaging analysis.}, journal = {Neurobiology of disease}, volume = {}, number = {}, pages = {107059}, doi = {10.1016/j.nbd.2025.107059}, pmid = {40818509}, issn = {1095-953X}, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a fatal central nervous system neurodegenerative disease, but the relationships among genetic mutations, plasma biomarkers, glymphatic system and clinical variables remain unclear.

METHODS: This study retrospectively collected data from April 2015 to November 2024 from the Department of Neurology of First Affiliated Hospital, Fujian Medical University, China. ALS patients (including genetic ALS (gALS) and sporadic ALS (sALS)), Alzheimer's disease (AD) patients, and healthy controls (HC) were included. Plasma glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), phosphorylated tau 181 (p-tau181), amyloid-beta 42 (Aβ42) and amyloid-beta 40 (Aβ40) concentrations were measured using ultrasensitive single molecule array (Simoa). All ALS individuals underwent genetic screening. The ALS Functional Rating Scale-Revised (ALSFRS-R) was used to assess motor function. The choroid plexus volume (CPV) and enlarged perivascular spaces (EPVS) were used to assess glymphatic function.

RESULTS: Firstly, we found that plasma levels of NfL (p < 0.001) and p-tau181 (p < 0.001) were significantly higher in ALS than in HC. Compared with sALS, gALS had a significantly higher plasma ptau181 (p < 0.05), Aβ42/40 ratio (p < 0.001). Secondly, gALS had more severe glymphatic dysfunction than sALS (p < 0.05), plasma GFAP (ρ = 0.57, p < 0.05) and p-tau181 (ρ = 0.58, p < 0.05) in gALS showed significant correlations with CPV. Thirdly, plasma GFAP was significantly associated with motor function (ρ = -0.35, p < 0.01) and its progression rate (ρ = 0.24, p < 0.05) in gALS.

CONCLUSIONS: The gALS exhibit a more severe and complex biomarker profile than sALS, in which plasma GFAP showed a significant correlation in disease progression.}, } @article {pmid40817956, year = {2025}, author = {Mannan, A and Sharma, A and Singh, TG}, title = {Boosting Brain Clean-Up: Can Targeting UPS Genes Offer Neuroprotection?.}, journal = {Molecular neurobiology}, volume = {}, number = {}, pages = {}, pmid = {40817956}, issn = {1559-1182}, abstract = {The ubiquitin-proteasome system (UPS) plays a critical role in protein homeostasis within eukaryotic cells. This review article examines the UPS's role in neuronal morphology and neurodegeneration through systematic analysis of current research. In neurodegenerative disorders (NDDs) such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS), UPS dysfunction contributes significantly to pathogenesis through accumulation of ubiquitinated misfolded proteins, disruption of cellular proteostasis, impaired substrate ubiquitination, and proteasomal deterioration. The UPS maintains normal central nervous system (CNS) function by regulating protein degradation. When this system fails, cellular proteostasis becomes compromised, accelerating neurodegeneration. Recent research has identified potential interventions for UPS activation through genetic modification and synthetic compounds. This review assesses how specific UPS components could serve as pharmacological targets for treating NDDs. By modulating UPS-mediated genes and pathways, novel therapeutic strategies may emerge for conditions including AD, PD, HD), and ALS. Current evidence suggests the UPS represents a promising therapeutic target for addressing the fundamental protein homeostasis disruptions underlying these devastating neurological conditions. Targeting this system could potentially slow disease progression by restoring proper protein degradation mechanisms and preventing toxic protein accumulation characteristic of NDDs.}, } @article {pmid40817583, year = {2025}, author = {Mandal, N and Skepö, M}, title = {Unraveling the Conformational Landscape of Amyloid Precursor Protein Intracellular Domain.}, journal = {Biophysical journal}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.bpj.2025.08.010}, pmid = {40817583}, issn = {1542-0086}, abstract = {The amyloid precursor protein intracellular domain (AICD), a cleavage product of Amyloid Precursor Protein (APP) implicated in Alzheimer's disease and Amyloid Lateral Sclerosis (ALS), is a functionally important but structurally elusive intrinsically disordered protein (IDP). In this study, we investigate the conformational ensemble of a 35-residue AICD segment encompassing the conserved YENPTY motif using molecular dynamics (MD) simulations, small-angle X-ray scattering (SAXS), circular dichroism (CD), and Nuclear Magnetic Resonance (NMR) data. Our results reveal that AICD fluctuates between compact and extended states, exhibiting dynamic secondary structure elements and heterogeneous solvent accessibility. SAXS and CD analyses support a partially compact, flexible ensemble, while time-lagged independent component analysis (tICA) uncovers metastable conformational states. Residue-specific solvent accessibility and hydrogen bonding patterns highlight transient structural stabilization, particularly within the YENPTY motif. These findings highlight the structural plasticity of AICD and offer insights into its potential for interaction and regulatory roles in nuclear signaling and neurodegeneration.}, } @article {pmid40815260, year = {2025}, author = {Jensen, KS}, title = {N-terminal acetylation of superoxide dismutase 1 accelerates amyloid formation without general destabilization of the apo state.}, journal = {Protein science : a publication of the Protein Society}, volume = {34}, number = {9}, pages = {e70267}, pmid = {40815260}, issn = {1469-896X}, support = {202004888//Vetenskapsrådet/ ; 20230966//Crafoordska Stiftelsen/ ; //Royal Physiographic Society of Lund/ ; 4002-00258//Natur og Univers, Det Frie Forskningsråd/ ; //Per-Eric and Ulla Schyberg's Foundation/ ; M23-0143//Åke Wiberg's Foundation/ ; }, abstract = {Co- and post-translational modifications can significantly impact the structure, dynamics, and function of proteins. In this study, we investigate how N-terminal acetylation affects misfolding and self-assembly of the enzyme superoxide dismutase 1 (SOD1), implicated in amyotrophic lateral sclerosis (ALS). Studies of protein inclusions in patient samples and animal models have shown that wild-type SOD1 can form amyloid fibrils even when no mutations are found in the sod1 gene. This has identified SOD1 amyloid formation as a possible common denominator of ALS and may suggest that co- and post-translational modifications, like N-terminal acetylation found in human SOD1, can be a factor in disease development. In this work, the impact of N-terminal acetylation of SOD1 on stability and aggregation is characterized. Results show that the structure and thermal stability of the apo state are unaffected by the modification while the amyloid formation rate is significantly enhanced. This is caused by a shortening of the nucleation phase together with an increase of fibril elongation by more than 10-fold upon N-terminal acetylation of SOD1. Collectively, the findings demonstrate how regulation by co- and post-translational modifications can influence protein misfolding and self-assembly.}, } @article {pmid40812817, year = {2025}, author = {Visser, M and de Mul, M and Ahaus, K and Weggelaar-Jansen, AM}, title = {Navigating value complexity in care pathway development: a qualitative case study.}, journal = {BMJ open}, volume = {15}, number = {8}, pages = {e098157}, pmid = {40812817}, issn = {2044-6055}, abstract = {OBJECTIVES: Care pathways (CPs) are widely used to standardise and improve healthcare delivery. However, CP development is often shaped by value (or normative) complexity. This study empirically explores how value complexity unfolds in a CP development programme.

DESIGN: A qualitative single-case study was conducted as part of a 2-year action research programme. The study followed a 'research-follow-action' strategy, in which action and learning occurred during the programme phase, followed by retrospective analysis using Greenhalgh et al's 'rules of thumb' as a reflective lens.

SETTING: A Dutch specialised rehabilitation hospital (13 sites, 800 employees approximately, ~16 000 patients annually). In three CP development cycles, 11 multidisciplinary teams were guided in CP development in a quality collaborative approach.

PARTICIPANTS: 26 respondents participated in 44 reflective conversations; 19 respondents completed reflective questionnaires and 169 participatory observation reports were included. Participants were purposively sampled and included representatives from the leadership triad (rehabilitation physicians, managers and healthcare professionals) and members of senior management involved in CP development.

RESULTS: Two overarching themes were identified: goal (mis)alignment and prolonged decision-making processes negatively impacted motivation and impeded CP development. Goal alignment between stakeholders was hindered by shifting organisational priorities, creating tensions between improving care quality and ensuring financial viability. Decision-making was challenged by role uncertainty and the complexities of multidisciplinary collaboration in CP development teams. Reflective dialogues, small-scale experimentation and financial modelling supported teams in navigating these tensions to varying degrees.

CONCLUSIONS: This study illustrates how value complexity unfolds in CP development and underscores the importance of ongoing stakeholder management, reflectivity, formative evaluation and dialogue. Greenhalgh et al's rules of thumb provided interpretive value in exploring these complexities but require a solid theoretical understanding and an awareness of the rules' interrelationships. A complexity-informed approach integrating ongoing reflection and adaptability can enrich CP development methodologies, enabling healthcare professionals and action researchers to engage constructively with value complexity in complex change processes. Further research is needed to develop and implement practical strategies for enhancing stakeholder engagement and decision-making in diverse healthcare settings.}, } @article {pmid40812811, year = {2025}, author = {Dougherty, M and Bartels, SM and Smith, JG and Zeliadt, SB and Hyde, J and Kim, B}, title = {The use of cost analysis in examinations of health coaching interventions: a scoping review protocol.}, journal = {BMJ open}, volume = {15}, number = {8}, pages = {e104082}, pmid = {40812811}, issn = {2044-6055}, abstract = {INTRODUCTION: Health coaching is the process of working with a trained coach, peer, or healthcare professional towards self-determined health and wellness goals. Health coaching is being increasingly adopted in multiple healthcare settings and has been shown to improve overall health outcomes and long-term maintenance of chronic conditions in multiple countries and healthcare settings. Research surrounding the costs of implementing health coaching and its effects on healthcare costs, particularly long-term costs, has been limited. Although analysis of healthcare costs has become an important priority in recent years, the available literature looking at the cost impacts of health coaching is small and inconclusive, finding mixed results with a variety of methodologies. This scoping review aims to identify gaps in the literature and help set a research agenda regarding the costs of health coaching implementation and its impacts.

METHODS AND ANALYSIS: The scoping review will be structured according to Levac et al's enhancement to Arksey and O'Malley's framework for conducting scoping reviews. PubMed, Embase, and the Health and Medicine Collection will be searched for peer-reviewed research that includes health and wellness coaching and some measurement of cost. Details about the type of study, cost analysis, methodology and results from the included articles will be extracted and summarised. Full-text publications, excluding editorials and opinion pieces, included in this scoping review will be published in 2017 or later, will be written in English, will align with the definition of health coaching as described by the National Board for Health and Wellness Coaching, and will include cost measurement. This review will include publications not captured in the previous integrative literature review looking at the cost-effectiveness of health coaching.

ETHICS AND DISSEMINATION: Findings will be disseminated through a peer-reviewed publication and through presentations to both health system and community-based entities currently using or considering adopting health coaching. Ethics approval is not a requirement for this review as no human research participants will be involved. All data will be obtained from publicly available literature, with no primary data generated.}, } @article {pmid40812017, year = {2025}, author = {Chahal, S and Debnath, A and Kumari, R and Ridhal, P and Sahoo, RK and Biswal, BK and Mishra, A and Siwach, P}, title = {Antihypertensive potential of diosgenin: A comparative pharmacoinformatics study.}, journal = {Computers in biology and medicine}, volume = {196}, number = {Pt C}, pages = {110911}, doi = {10.1016/j.compbiomed.2025.110911}, pmid = {40812017}, issn = {1879-0534}, abstract = {The angiotensin II type 1 receptor (AT1R) is an important target protein involved in the regulation of hypertension, a major public health concern affecting 1.28 billion individuals globally. The existing drugs have serious side-effects on medium to long term use, and therefore, search for safer and more effective drug molecules is highly needed. This study explores the antihypertensive potential of thirty-six natural terpenoids targeting the AT1R, with Allisartan isoproxil (active form, LCA) used as a positive control. After initial screening based on the Lipinski rule of five and in silico ADMET profiling, twenty-five terpenoids were selected for molecular docking studies. Diosgenin and Neoandrographolide emerged as lead compounds with superior binding affinities compared to std. drug, LCA. Diosgenin's favorable non-toxic profile (class 6) and significant molecular interactions with critical amino acids in AT1R make it a strong candidate for further validation through MD studies. Molecular dynamics simulations at a microsecond revealed protein stability by reducing fluctuations, a compact and more stable contact exhibited by Diosgenin. Furthermore, MM-PBSA analysis showed a stronger binding affinity and thermodynamic stability of Diosgenin compared to LCA. Diosgenin exhibited no cytotoxicity in HaCaT normal keratinocyte cells at concentrations up to 22 μM (24 h) and 20 μM (48 h), as determined by in vitro validation, indicating its safety for further therapeutic evaluation. Additionally, PPI network and hub genes analysis identified potential molecular targets for Diosgenin, including SRC, ABL1, IGF1R, and JAK2, suggesting possible mechanistic role. Diosgenin is a promising natural therapeutic candidate for hypertension treatment, which could regulate vascular function, smooth muscle cell activity, and endothelial function via various mechanisms by influencing IGF1R, JAK2, KIT, MDM2, MET, and IL2 demonstrated through KEGG pathway analysis.}, } @article {pmid40808712, year = {2025}, author = {Farrokhi, Z and Zakavi, SA and Sarafraz, A and Valifard, M and Yousefzadeh, S and Mashhadi Tafreshi, Z and Anbiyaee, O and Rostami, N and Asadi Anar, M and Deravi, N}, title = {Acoustic signatures of bulbar ALS: Predictive modeling with sustained vowels and LightGBM.}, journal = {eNeurologicalSci}, volume = {40}, number = {}, pages = {100579}, pmid = {40808712}, issn = {2405-6502}, abstract = {BACKGROUND: Amyotrophic Lateral Sclerosis (ALS) is a degenerative neurologic disease with no definitive biomarkers for early detection. This paper discusses the use of acoustic analysis of sustained vowel phonations (SVP) and machine learning in ALS detection.

METHODS: An SVP corpus of 128 (64 /a/ and 64 /i/) from 31 patients with ALS and 33 healthy controls (HC) was employed. 131 acoustic features, including jitter, shimmer, Mel-Frequency Cepstral Coefficients (MFCCs), and Pathological Vibrato Index (PVI), were extracted. A LightGBM (Light Gradient Boosting Machine)-based model was built and optimized using 5-fold cross-validation to separate ALS cases. Model performance and feature importance were evaluated.

RESULTS: The model performed well with high predictability, yielding an RMSLE of 0.162 and most predictions closely correlating with actual diagnoses. The top features obtained were S55_i, CCI(2), and dCCa(12), which were consistently at the top of the ranking list, indicating their role in ALS detection. The PVI was determined to be a significant biomarker with high values having high correlations with ALS diagnoses. But the multimodal nature of the predictive values indicated some flaws in generalization.

CONCLUSION: This paper demonstrates the applicability of acoustic analysis and machine learning for early ALS detection. The proposed method provides an affordable, low-cost, and non-invasive way for ALS diagnosis with potential for application in telemedicine and clinical settings. Future research must expand datasets and integrate additional diagnostic modalities to improve the model's robustness and clinical translation.}, } @article {pmid40808471, year = {2025}, author = {Zhang, L and Cai, L and Lin, H and Wu, W and Zhu, Y and Cai, J and Hu, C and Lin, X and Sun, H and Wei, X}, title = {Two Birds With One Stone: The Protective Role of the Antidiabetic Drug Sodium-Glucose Cotransporter-2 Inhibitor in Neurodegenerative Diseases.}, journal = {The European journal of neuroscience}, volume = {62}, number = {3}, pages = {e70221}, doi = {10.1111/ejn.70221}, pmid = {40808471}, issn = {1460-9568}, support = {2021J01397//Natural Science Foundation of Fujian, China/ ; 2022GGA010//Fujian Provincial Health Technology Project/ ; 2023Y9347//Fujian Provincial Joint Funding Project of Scientific and Technological Innovation/ ; 2023Y9298//Fujian Provincial Joint Funding Project of Scientific and Technological Innovation/ ; 2023Y9343//Fujian Provincial Joint Funding Project of Scientific and Technological Innovation/ ; }, abstract = {The neuroprotective role of sodium-glucose cotransporter-2 inhibitor (SGLT2i) has attracted considerable interest. The purpose of this study was to investigate the role of SGLT2i in several common neurodegenerative diseases (NDs), including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS). Utilizing drug-target Mendelian randomization (MR) and colocalization, we used single nucleotide polymorphisms (SNPs) proximal to the SLC5A2 gene to analyze the influence of SGLT2i on AD, PD, ALS, and MS. Sensitivity analyses were performed to assess heterogeneity and pleiotropy. Phenome-wide association study (PheWAS) was used to probe the relationship of SGLT2i with other characteristics. Protein-protein interaction (PPI) networks were used to explore how SLC5A2 affects other proteins, and enrichment analysis was used to explore possible biological processes. The MR analysis showed that SGLT2i was negatively associated with AD (OR = 0.77, p = 0.01), PD (OR = 0.52, p = 0.04), ALS (OR = 0.60, p = 0.01), and MS (OR = 0.33, p = 0.027), indicating that SGLT2i could reduce the risk of AD by 23%, PD by 48%, ALS by 40%, and MS by 67%. The colocalization supported this conclusion. The PheWAS showed that SGLT2i was associated with body mass index and systolic blood pressure. SGLT2i is biologically closely related to the development of NDs. This study suggested that SGLT2i was able to reduce the risk of NDs. SGLT2i may perform this process through many mechanisms. This study provides a new perspective on the treatment of NDs; clinical trials and relevant experiments are necessary to further validate the neuroprotective effects of SGLT2i.}, } @article {pmid40807722, year = {2025}, author = {Lee, S and Lee, S}, title = {Text Typing Using Blink-to-Alphabet Tree for Patients with Neuro-Locomotor Disabilities.}, journal = {Sensors (Basel, Switzerland)}, volume = {25}, number = {15}, pages = {}, pmid = {40807722}, issn = {1424-8220}, support = {IITP-2025-RS-2024-00436765//the Korea government(MSIT)/ ; 2025//KOREATECH/ ; }, abstract = {Lou Gehrig's disease, also known as ALS, is a progressive neurodegenerative condition that weakens muscles and can lead to paralysis as it progresses. For patients with severe paralysis, eye-tracking devices such as eye mouse enable communication. However, the equipment is expensive, and the calibration process is very difficult and frustrating for patients to use. To alleviate this problem, we propose a simple and efficient method to type texts intuitively with graphical guidance on the screen. Specifically, the method detects patients' eye blinks in video frames to navigate through three sequential steps, narrowing down the choices from 9 letters, to 3 letters, and finally to a single letter (from a 26-letter alphabet). In this way, a patient is able to rapidly type a letter of the alphabet by blinking a minimum of three times and a maximum of nine times. The proposed method integrates an API of large language model (LLM) to further accelerate text input and correct sentences in terms of typographical errors, spacing, and upper/lower case. Experiments on ten participants demonstrate that the proposed method significantly outperforms three state-of-the-art methods in both typing speed and typing accuracy, without requiring any calibration process.}, } @article {pmid40806770, year = {2025}, author = {Sharbafshaaer, M and Pepe, R and Notariale, R and Canale, F and Tessitore, A and Tedeschi, G and Trojsi, F}, title = {Neuroaxonal Degeneration as a Converging Mechanism in Motor Neuron Diseases (MNDs): Molecular Insights into RNA Dysregulation and Emerging Therapeutic Targets.}, journal = {International journal of molecular sciences}, volume = {26}, number = {15}, pages = {}, pmid = {40806770}, issn = {1422-0067}, support = {PERMEALS PNRR-MAD-2022-12375731//Italian Ministry of Health/ ; }, abstract = {Motor Neuron Diseases (MNDs) such as Amyotrophic Lateral Sclerosis (ALS), Primary Lateral Sclerosis (PLS), Hereditary Spastic Paraplegia (HSP), Spinal Muscular Atrophy with Respiratory Distress Type 1 (SMARD1), Multisystem Proteinopathy (MSP), Spinal and Bulbar Muscular Atrophy (SBMA), and ALS associated to Frontotemporal Dementia (ALS-FTD), have traditionally been studied as distinct entities, each one with unique genetic and clinical characteristics. However, emerging research reveals that these seemingly disparate conditions converge on shared molecular mechanisms that drive progressive neuroaxonal degeneration. This narrative review addresses a critical gap in the field by synthesizing the most recent findings into a comprehensive, cross-disease mechanisms framework. By integrating insights into RNA dysregulation, protein misfolding, mitochondrial dysfunction, DNA damage, kinase signaling, axonal transport failure, and immune activation, we highlight how these converging pathways create a common pathogenic landscape across MNDs. Importantly, this perspective not only reframes MNDs as interconnected neurodegenerative models but also identifies shared therapeutic targets and emerging strategies, including antisense oligonucleotides, autophagy modulators, kinase inhibitors, and immunotherapies that transcend individual disease boundaries. The diagnostic and prognostic potential of Neurofilament Light Chain (NfL) biomarkers is also emphasized. By shifting focus from gene-specific to mechanism-based approaches, this paper offers a much-needed roadmap for advancing both research and clinical management in MNDs, paving the way for cross-disease therapeutic innovations.}, } @article {pmid40806624, year = {2025}, author = {Șerban, M and Toader, C and Covache-Busuioc, RA}, title = {The Redox Revolution in Brain Medicine: Targeting Oxidative Stress with AI, Multi-Omics and Mitochondrial Therapies for the Precision Eradication of Neurodegeneration.}, journal = {International journal of molecular sciences}, volume = {26}, number = {15}, pages = {}, pmid = {40806624}, issn = {1422-0067}, abstract = {Oxidative stress is a defining and pervasive driver of neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). As a molecular accelerant, reactive oxygen species (ROS) and reactive nitrogen species (RNS) compromise mitochondrial function, amplify lipid peroxidation, induce protein misfolding, and promote chronic neuroinflammation, creating a positive feedback loop of neuronal damage and cognitive decline. Despite its centrality in promoting disease progression, attempts to neutralize oxidative stress with monotherapeutic antioxidants have largely failed owing to the multifactorial redox imbalance affecting each patient and their corresponding variation. We are now at the threshold of precision redox medicine, driven by advances in syndromic multi-omics integration, Artificial Intelligence biomarker identification, and the precision of patient-specific therapeutic interventions. This paper will aim to reveal a mechanistically deep assessment of oxidative stress and its contribution to diseases of neurodegeneration, with an emphasis on oxidatively modified proteins (e.g., carbonylated tau, nitrated α-synuclein), lipid peroxidation biomarkers (F2-isoprostanes, 4-HNE), and DNA damage (8-OHdG) as significant biomarkers of disease progression. We will critically examine the majority of clinical trial studies investigating mitochondria-targeted antioxidants (e.g., MitoQ, SS-31), Nrf2 activators (e.g., dimethyl fumarate, sulforaphane), and epigenetic reprogramming schemes aiming to re-establish antioxidant defenses and repair redox damage at the molecular level of biology. Emerging solutions that involve nanoparticles (e.g., antioxidant delivery systems) and CRISPR (e.g., correction of mutations in SOD1 and GPx1) have the potential to transform therapeutic approaches to treatment for these diseases by cutting the time required to realize meaningful impacts and meaningful treatment. This paper will argue that with the connection between molecular biology and progress in clinical hyperbole, dynamic multi-targeted interventions will define the treatment of neurodegenerative diseases in the transition from disease amelioration to disease modification or perhaps reversal. With these innovations at our doorstep, the future offers remarkable possibilities in translating network-based biomarker discovery, AI-powered patient stratification, and adaptive combination therapies into individualized/long-lasting neuroprotection. The question is no longer if we will neutralize oxidative stress; it is how likely we will achieve success in the new frontier of neurodegenerative disease therapies.}, } @article {pmid40806541, year = {2025}, author = {Bedja-Iacona, L and Forget, A and Boisseau, C and Marouillat, S and Chudinova, A and Veyrat-Durebex, C and Guissart, C and Lumbroso, S and Raoul, C and Andres, CR and Blasco, H and Couratier, P and Corcia, P and Verschueren, A and Mouzat, K and Vourc'h, P}, title = {Improving ALS Molecular Diagnosis Through Functional Assays: Reassessment of a SOD1 Variant of Uncertain Significance.}, journal = {International journal of molecular sciences}, volume = {26}, number = {15}, pages = {}, pmid = {40806541}, issn = {1422-0067}, abstract = {Genetic testing in amyotrophic lateral sclerosis (ALS) often reveals variants of uncertain significance (VUS), which are frequently omitted from diagnostic reports or reported with limited clinical interpretation. To address this gap, we developed a rapid functional assessment pipeline in collaboration with FILSLAN, the French ALS care network, combining in vitro and in vivo neurogenetic assays. We illustrate this approach through the reclassification of the SOD1 p.Val120Leu variant, identified in an ALS patient, as pathogenic. Functional studies demonstrated that this variant leads to cytoplasmic aggregation, reduced neurite outgrowth, and abnormal motor behavior in zebrafish. These results support the systematic use of functional assays to clarify the pathogenicity of uncertain variants, thereby improving diagnostic accuracy, preventing misdiagnosis, and enabling timely therapeutic interventions in ALS.}, } @article {pmid40806469, year = {2025}, author = {Wang, J and Shen, Y and Liao, P and Yang, B and Jiang, R}, title = {Roles of Ion Channels in Oligodendrocyte Precursor Cells: From Physiology to Pathology.}, journal = {International journal of molecular sciences}, volume = {26}, number = {15}, pages = {}, pmid = {40806469}, issn = {1422-0067}, support = {82401445//National Natural Science Foundation of China/ ; 82271249//National Natural Science Foundation of China/ ; 2024M752251//China Postdoctoral Science Foundation/ ; 2024NSFSC1636//Sichuan Science and Technology Program/ ; 2024HXBH013//Post doctor Research Fund of West China Hospital of Sichuan University/ ; ZYYC23002//1-3-5 Project for Disciplines of Excellence of West China Hospital of Sichuan University/ ; GZC20241141//Postdoctoral Fellowship Program of CPSF/ ; }, abstract = {Oligodendrocyte precursor cells (OPCs) are a distinct and dynamic glial population that retain proliferative and migratory capacities throughout life. While traditionally recognized for differentiating into oligodendrocytes (OLs) and generating myelin to support rapid nerve conduction, OPCs are now increasingly appreciated for their diverse and non-canonical roles in the central nervous system (CNS), including direct interactions with neurons. A notable feature of OPCs is their expression of diverse ion channels that orchestrate essential cellular functions, including proliferation, migration, and differentiation. Given their widespread distribution across the CNS, OPCs are increasingly recognized as active contributors to the development and progression of various neurological disorders. This review aims to present a detailed summary of the physiological and pathological functions of ion channels in OPCs, emphasizing their contribution to CNS dysfunction. We further highlight recent advances suggesting that ion channels in OPCs may serve as promising therapeutic targets across a broad range of disorders, including, but not limited to, multiple sclerosis (MS), spinal cord injury, amyotrophic lateral sclerosis (ALS), psychiatric disorders, Alzheimer's disease (AD), and neuropathic pain (NP). Finally, we discuss emerging therapeutic strategies targeting OPC ion channel function, offering insights into potential future directions in the treatment of CNS diseases.}, } @article {pmid40806377, year = {2025}, author = {Ghosh, M and Bayat, AH and Pearse, DD}, title = {Small Extracellular Vesicles in Neurodegenerative Disease: Emerging Roles in Pathogenesis, Biomarker Discovery, and Therapy.}, journal = {International journal of molecular sciences}, volume = {26}, number = {15}, pages = {}, pmid = {40806377}, issn = {1422-0067}, abstract = {Neurodegenerative diseases (NDDs) such as Alzheimer's, Parkinson's, ALS, and Huntington's pose a growing global challenge due to their complex pathobiology and aging demographics. Once considered as cellular debris, small extracellular vesicles (sEVs) are now recognized as active mediators of intercellular signaling in NDD progression. These nanovesicles (~30-150 nm), capable of crossing the blood-brain barrier, carry pathological proteins, RNAs, and lipids, facilitating the spread of toxic species like Aβ, tau, TDP-43, and α-synuclein. sEVs are increasingly recognized as valuable diagnostic tools, outperforming traditional CSF biomarkers in early detection and disease monitoring. On the therapeutic front, engineered sEVs offer a promising platform for CNS-targeted delivery of siRNAs, CRISPR tools, and neuroprotective agents, demonstrating efficacy in preclinical models. However, translational hurdles persist, including standardization, scalability, and regulatory alignment. Promising solutions are emerging, such as CRISPR-based barcoding, which enables high-resolution tracking of vesicle biodistribution; AI-guided analytics to enhance quality control; and coordinated regulatory efforts by the FDA, EMA, and ISEV aimed at unifying identity and purity criteria under forthcoming Minimal Information for Studies of Extracellular Vesicles (MISEV) guidelines. This review critically examines the mechanistic roles, diagnostic potential, and therapeutic applications of sEVs in NDDs, and outlines key strategies for clinical translation.}, } @article {pmid40806220, year = {2025}, author = {Blaudin de Thé, FX and Klemann, CJHM and De Witte, W and Widomska, J and Delagrange, P and Mannoury La Cour, C and Fouesnard, M and Elouej, S and Mayl, K and Lévy, N and Krupp, J and Jeggo, R and Moingeon, P and Poelmans, G}, title = {Identifying Therapeutic Targets for Amyotrophic Lateral Sclerosis Through Modeling of Multi-Omics Data.}, journal = {International journal of molecular sciences}, volume = {26}, number = {15}, pages = {}, pmid = {40806220}, issn = {1422-0067}, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that primarily affects motor neurons, leading to loss of muscle control, and, ultimately, respiratory failure and death. Despite some advances in recent years, the underlying genetic and molecular mechanisms of ALS remain largely elusive. In this respect, a better understanding of these mechanisms is needed to identify new and biologically relevant therapeutic targets that could be developed into treatments that are truly disease-modifying, in that they address the underlying causes rather than the symptoms of ALS. In this study, we used two approaches to model multi-omics data in order to map and elucidate the genetic and molecular mechanisms involved in ALS, i.e., the molecular landscape building approach and the Patrimony platform. These two methods are complementary because they rely upon different omics data sets, analytic methods, and scoring systems to identify and rank therapeutic target candidates. The orthogonal combination of the two modeling approaches led to significant convergences, as well as some complementarity, both for validating existing therapeutic targets and identifying novel targets. As for validating existing targets, we found that, out of 217 different targets that have been or are being investigated for drug development, 10 have high scores in both the landscape and Patrimony models, suggesting that they are highly relevant for ALS. Moreover, through both models, we identified or corroborated novel putative drug targets for ALS. A notable example of such a target is MATR3, a protein that has strong genetic, molecular, and functional links with ALS pathology. In conclusion, by using two distinct and highly complementary disease modeling approaches, this study enhances our understanding of ALS pathogenesis and provides a framework for prioritizing new therapeutic targets. Moreover, our findings underscore the potential of leveraging multi-omics analyses to improve target discovery and accelerate the development of effective treatments for ALS, and potentially other related complex human diseases.}, } @article {pmid40806146, year = {2025}, author = {Coutinho, KMD and Rabelo, H and Fernandes, F and Coutinho, KD and Valentim, RAM and Dias, AP and Valentim, JLRDS and Batista, NADN and Romão, MH and Cunha, PSD and Cunha-Oliveira, A and Henriques, S and de Melo, LP and Vale, SHL and Leite-Lais, L and de Lima, KC}, title = {Effectiveness of a Learning Pathway on Food and Nutrition in Amyotrophic Lateral Sclerosis.}, journal = {Nutrients}, volume = {17}, number = {15}, pages = {}, pmid = {40806146}, issn = {2072-6643}, support = {TED 132/2018//Ministério da Saúde/ ; }, abstract = {Background/Objectives: Health education plays a vital role in training health professionals and caregivers, supporting both prevention and the promotion of self-care. In this context, technology serves as a valuable ally by enabling continuous and flexible learning. Among the various domains of health education, nutrition stands out as a key element in the management of Amyotrophic Lateral Sclerosis (ALS), helping to prevent malnutrition and enhance patient well-being. Accordingly, this study aimed to evaluate the effectiveness of the teaching and learning processes within a learning pathway focused on food and nutrition in the context of ALS. Methods: This study adopted a longitudinal, quantitative design. The learning pathway, titled "Food and Nutrition in ALS," consisted of four self-paced and self-instructional Massive Open Online Courses (MOOCs), offered through the Virtual Learning Environment of the Brazilian Health System (AVASUS). Participants included health professionals, caregivers, and patients from all five regions of Brazil. Participants had the autonomy to complete the courses in any order, with no prerequisites for enrollment. Results: Out of 14,263 participants enrolled nationwide, 182 were included in this study after signing the Informed Consent Form. Of these, 142 (78%) completed at least one course and participated in the educational intervention. A significant increase in knowledge was observed, with mean pre-test scores rising from 7.3 (SD = 1.8) to 9.6 (SD = 0.9) on the post-test across all courses (p < 0.001). Conclusions: The self-instructional, technology-mediated continuing education model proved effective in improving participants' knowledge about nutrition in ALS. Future studies should explore knowledge retention, behavior change, and the impact of such interventions on clinical outcomes, especially in multidisciplinary care settings.}, } @article {pmid40802071, year = {2025}, author = {Yamashita, T and Yokota, O and Ousaka, D and Sun, H and Haraguchi, T and Ota-Elliott, RS and Matsuoka, C and Kawano, T and Nakashima-Yasuda, H and Fukui, Y and Nakano, Y and Morihara, R and Hasegawa, M and Hosono, Y and Terada, S and Takaki, M and Ishiura, H}, title = {Biallelic variants in DNAJC7 cause familial amyotrophic lateral sclerosis with the TDP-43 pathology.}, journal = {Acta neuropathologica}, volume = {150}, number = {1}, pages = {19}, pmid = {40802071}, issn = {1432-0533}, support = {JP23K08543//Japan Society for the Promotion of Science/ ; JP23K10450//Japan Society for the Promotion of Science/ ; JP23K27514//Japan Society for the Promotion of Science/ ; JP24wm0425019//Japan Agency for Medical Research and Development/ ; JP23ek0109673//Japan Agency for Medical Research and Development/ ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by the progressive degeneration of motor neurons. ALS pathology primarily involves the failure of protein quality control mechanisms, leading to the accumulation of misfolded proteins, particularly TAR DNA-binding protein 43 (TDP-43). TDP-43 aggregation is a central pathological feature of ALS. Maintaining protein homeostasis is critical and facilitated by heat shock proteins (HSPs), particularly the HSP40 family, which includes co-chaperones such as DNAJC7. Here, we report a family with three siblings affected by ALS who carry a homozygous c.518dupC frameshift variant in DNAJC7, a member of the HSP40 family. All three patients exhibited progressive muscle weakness, limb atrophy, bulbar palsy, and respiratory failure. Pathological examination revealed degeneration of both upper and lower motor neurons, with phosphorylated TDP-43-positive neuronal cytoplasmic inclusions in the frontal and temporal cortices. Immunoblot analysis were consistent with a type B pattern of phosphorylated TDP-43 in the precentral gyrus. Immunohistochemistry and RNA sequencing analyses demonstrated a substantial reduction in DNAJC7 expression at both the protein and RNA levels in affected brain regions. In a TDP-43 cell model, DNAJC7 knockdown impaired the disassembly of TDP-43 following arsenite-induced stress, whereas DNAJC7 overexpression suppressed the assembly and promoted the disassembly of arsenite-induced TDP-43 condensates. Furthermore, in a zebrafish ALS model, dnajc7 knockdown resulted in increased TDP-43 aggregation in motor neurons and reduced survival. To the best of our knowledge, this study provides the first evidence linking biallelic loss-of-function variants in DNAJC7 to familial ALS with TDP-43 pathology.}, } @article {pmid40801981, year = {2025}, author = {Goleij, P and Amini, A and Sanaye, PM and Heidari, MM and Tabari, MAK and Aschner, M and Larsen, DS and Khan, H and Daglia, M}, title = {The IL-12 family cytokines in neurodegenerative diseases: dual roles in neurotoxicity and neuroprotection.}, journal = {Inflammopharmacology}, volume = {}, number = {}, pages = {}, pmid = {40801981}, issn = {1568-5608}, abstract = {Neurodegenerative diseases (NDs) such as Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS) are characterized by progressive neuronal loss and chronic neuroinflammation. Increasing evidence highlights the interleukin-12 (IL-12) cytokine family-including IL-12, IL-23, IL-27, and IL-35-as central regulators of immune responses in the central nervous system (CNS). IL-12 and IL-23 predominantly promote pro-inflammatory pathways by driving Th1/Th17 activity, microglial activation, and neurotoxicity, whereas IL-27 and IL-35 exert anti-inflammatory and neuroprotective effects through IL-10 induction and expansion of regulatory immune subsets. This review synthesizes disease-specific expression patterns and experimental findings, underscoring the dual pathogenic and protective roles of these cytokines. Therapeutic strategies targeting IL-12 family signaling have shown promise in preclinical and clinical contexts. In AD, blockade of IL-12/IL-23 reduced amyloid burden and improved cognition, while agents such as tadalafil and bergapten enhanced IL-27-mediated neuroprotection via PI3K/Akt, Wnt/β-catenin, and cGMP/PKG pathways. In MS, approaches including p40 blockade (ustekinumab, ABT-874), interferon-β therapy, hematopoietic stem cell transplantation, and B-cell depletion (ocrelizumab) variably suppressed IL-12/IL-23 and augmented IL-27/IL-35, influencing relapse rates and progression. Natural compounds such as curcumin, berberine, and vitamin D further highlight metabolic and dietary opportunities for cytokine modulation. In PD, combinatorial regimens combining herbal formulations with anti-inflammatory agents dampened IL-12-driven macrophage activation and supported dopaminergic neuron survival. Taken together, IL-12 family cytokines emerge as both biomarkers and therapeutic targets in NDs. However, context-dependent activity, blood-brain barrier constraints, and incomplete understanding-particularly of IL-35-pose translational challenges warranting further investigation.}, } @article {pmid40801430, year = {2025}, author = {Foster-Powell, A and Rostami-Hodjegan, A and Meno-Tetang, G and Mager, DE and Ogungbenro, K}, title = {Mathematical Modeling of Neuroinflammation in Neurodegenerative Diseases.}, journal = {CPT: pharmacometrics & systems pharmacology}, volume = {}, number = {}, pages = {}, doi = {10.1002/psp4.70064}, pmid = {40801430}, issn = {2163-8306}, support = {BB/W509930/1//Biotechnology and Biosciences Research Council (BBSRC) Industrial CASE studentship in collaboration with AstraZeneca (AZ), UK/ ; }, abstract = {Age-related neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD) and Parkinson's disease (PD) are an increasing public health concern. Whereas the pathology of these diseases is complex, chronic central inflammation, or neuroinflammation, is commonly observed across many neurodegenerative diseases. Despite a huge wealth of resources and promising preclinical testing, effective disease-modifying therapies do not exist. This failure is owing to a combination of poor biological understanding of this response, unsuitable animal models, and poor scaling from pathway up to clinical levels. In order to address these challenges, systems-level mathematical models may be utilized. Here, we provide a background on neuroinflammation and summarize available mathematical models of this response. Models described by ordinary, partial, and delay differential equations, and Boolean logic are introduced and discussed. The results as discussed in this review suggest logic-based modeling as a formalism capable of managing the challenges associated with the modeling of CNS diseases.}, } @article {pmid40799366, year = {2025}, author = {Gao, B and Wang, L and Gong, J and Zhu, Z and Liu, Q and Yuan, H and Wang, H}, title = {The interplay between physical exercise and autophagy signaling in brain health, neurodegenerative diseases and aging.}, journal = {Frontiers in aging neuroscience}, volume = {17}, number = {}, pages = {1579208}, pmid = {40799366}, issn = {1663-4365}, abstract = {Brain health is increasingly recognized as a critical component of overall wellbeing, particularly concerning neurodegenerative diseases, which are characterized by the progressive degeneration of the nervous system. Conditions such as Alzheimer's disease (AD) and Parkinson's disease, together with less common disorders, resembling Amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD), significantly impact cognitive and physical health, affecting over 50 million individuals worldwide. This review explores the multifaceted relationship between brain health and neurodegeneration, emphasizing the roles of biological, environmental, and lifestyle factors. Notably, physical activity has been identified as a potent intervention that enhances neuroplasticity and metabolic resilience while mitigating the effects of neurodegeneration. Research indicates that exercise activates autophagy, which is crucial for clearing neurotoxic aggregates like amyloid-beta and α-synuclein, thereby promoting neuronal health. Additionally, exercise stimulates the production of neurotrophic factors such as BDNF and GDNF, which are essential for neuronal survival and function. Despite the promising findings regarding exercise as a preventive and therapeutic strategy for neurodegenerative diseases, further investigation into the underlying mechanisms is necessary to optimize these interventions. This review aims to elucidate the complex interactions between exercise, autophagy, and brain health to provide insights into effective strategies for combating neurodegeneration.}, } @article {pmid40798859, year = {2025}, author = {Vijaya Bhaskar, AV and Vijayakumar, I and Torra, J and Runge, F and Hennessy, M and Forristal, PD}, title = {Insights into ALS-inhibiting herbicide resistance in Poa annua in an arable cropping system.}, journal = {Pest management science}, volume = {}, number = {}, pages = {}, doi = {10.1002/ps.70121}, pmid = {40798859}, issn = {1526-4998}, support = {//Department of Agriculture, Food and the Marine, Ireland/ ; }, abstract = {BACKGROUND: Dependence on a single herbicide type to control a broad-spectrum of weeds has resulted in cases of resistance to acetolactate synthase (ALS) inhibitors in weeds normally considered lower priority such as Poa annua, being recorded in winter wheat fields in Ireland. This study characterizes resistance to ALS-inhibiting sulfonylureas (SU), sulfonylamino-carbonyl-triazolinones (SCT) and triazolopyrimidine (TP) herbicides in five resistance-suspect populations (POAAN-R1 to POAAN-R5).

RESULTS: Variability in cross-resistance levels were noted in the POAAN-R populations, correlating with target-site mutations and specific amino acid substitutions. Mutations Pro-197-Thr in POAAN-R1, Pro-197-Thr + Trp-574-Leu in POAAN-R4, and Trp-574-Leu in POAAN-R5 confer high levels of resistance to SU, SU + SCT and TP herbicides (GR50 resistance index, RI >10). In POAAN-R2, Pro-197-Gln confers high resistance to SU and SU + SCT (RI >10) and low resistance to TP (RI = 3.2). POAAN-R3 with Pro-197-Thr + Pro-197-Gln, confers moderate resistance to SU and SU + SCT (RI >5) and high resistance to TP (RI >10). All sequenced plants had homozygous mutations that evolved independently in ALS1 (Pro-197-Gln) or ALS2 (Pro-197-Thr or Trp-574-Leu) isoforms. Among the alternative non-residual herbicides evaluated, clethodim and glyphosate effectively controlled P. annua populations.

CONCLUSION: Pro-197-Thr and/or Pro-197-Gln, as well as the combination of Pro-197-Thr + Trp-574-Leu were identified for the first time in P. annua in this study. As cultural/non-chemical management of P. annua is challenging, the primary control in cereal crops will likely be the use of non-ALS herbicide modes of action, including the application of pre-emergence or autumn residual-type herbicides. © 2025 The Author(s). Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.}, } @article {pmid40797499, year = {2025}, author = {Wang, X and Cui, H and Xu, Z}, title = {Reevaluating the diagnosis of right coronary artery absence: A thoughtful analysis of a case report.}, journal = {Medicine}, volume = {104}, number = {32}, pages = {e43620}, pmid = {40797499}, issn = {1536-5964}, abstract = {RATIONALE: This reevaluation challenges the diagnostic certainty of coronary angiography (CAG) and computed tomography angiography (CTA) in confirming right coronary artery (RCA) agenesis, as presented in Seok Oh et al's case. It underscores the critical need for multimodal imaging to avoid misdiagnosis of rare coronary anomalies.

PATIENT CONCERNS: A 57-year-old male presented with severe chest pain lasting several hours, accompanied by hemodynamic instability and ST-segment elevation consistent with myocardial infarction.

DIAGNOSES: CAG revealed total occlusion of the left circumflex artery (LCX) and suggested that the RCA territory was supplied by a superdominant LCX. Coronary CTA later indicated the absence of the RCA, though diagnostic uncertainties remained.

INTERVENTIONS: Emergent percutaneous coronary intervention was performed to address the LCX occlusion, resulting in clinical stabilization.

OUTCOMES: Reanalysis of published CAG images revealed no definitive evidence of LCX extending to RCA territory. CTA suggested the "RCA-supplying branch" was likely a coronary vein, implying possible misinterpretation of a left-dominant system with anomalous small RCA.

LESSONS: This case highlights the challenges of diagnosing rare coronary anomalies and emphasizes the importance of multi-modal imaging for accurate evaluation and decision-making.}, } @article {pmid40796666, year = {2025}, author = {Lowry, ER and Patel, T and Costa, JA and Chang, E and Tariq, S and Melikyan, H and Davis, I and Aziz, S and Ntermentzaki, G and Lotti, F and Wichterle, H}, title = {Embryonic motor neuron programming factors reactivate immature gene expression and suppress ALS pathologies in postnatal motor neurons.}, journal = {Nature neuroscience}, volume = {}, number = {}, pages = {}, pmid = {40796666}, issn = {1546-1726}, support = {R01NS140764//U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; K99NS121136//U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; R01NS116141//U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; R01NS109217//U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; }, abstract = {Aging is a major risk factor in amyotrophic lateral sclerosis (ALS) and other adult-onset neurodegenerative disorders. Whereas young neurons are capable of buffering disease-causing stresses, mature neurons lose this ability and degenerate over time. We hypothesized that the resilience of young motor neurons could be restored by reexpression of the embryonic motor neuron selector transcription factors ISL1 and LHX3. We found that viral reexpression of ISL1 and LHX3 selectively in postnatal motor neurons reactivates aspects of their youthful gene expression program and alleviates key disease-relevant phenotypes in the SOD1[G93A] mouse model of ALS. Our results suggest that redeployment of lineage-specific neuronal selector transcription factors can be an effective strategy to attenuate age-dependent phenotypes in neurodegenerative disease.}, } @article {pmid40796055, year = {2025}, author = {Tedeschi, V and Ciancio, R and Magliocca, G and Esposito, E and Piccirillo, S and Rubino, V and Preziuso, A and Spadoni, T and Muraglia, ND and Ruggiero, G and Pannaccione, A and Secondo, A}, title = {Lysosomal TPC2 channel as a new target of chlorpromazine and clomipramine to induce protective autophagy in L-BMAA-induced neurodegeneration.}, journal = {Biochemical pharmacology}, volume = {242}, number = {Pt 2}, pages = {117219}, doi = {10.1016/j.bcp.2025.117219}, pmid = {40796055}, issn = {1873-2968}, abstract = {Several neurodegenerative diseases including amyotrophic lateral sclerosis (ALS) are characterized by toxic aggregates accumulation due to autophagy blockade, prompting researchers to identify new autophagy-activating drugs. Here we tested, in an in vitro ALS/PDC model, the neuroprotective effects of the antipsychotic Chlorpromazine (CPZ) and the antidepressant Clomipramine (CMI), chosen by drug repurposing approach for their ability to stimulate TPC2 lysosomal channel. Patch-clamp electrophysiology on enlarged lysosomes in NSC-34 motor neurons showed that CPZ and CMI induced large inwardly-rectifying currents, that were inhibited by TPC2 synthetic blocker trans-Ned-19. The same currents were evoked by TPC2 endogenous agonist NAADP and its mimetic agent TPC2-A1-N, and inhibited by trans-Ned-19 and siRNAs against TPC2 (siTPC2). CPZ and CMI elicited a significant [Ca[2+]]i increase that rapidly induced nuclear translocation of TFEB (transcription factor EB), the master regulator of autophagy. Accordingly, TPC2 stimulation by both the drugs boosted autophagy, as revealed by the activation of autophagy initiators ULK and AMPK α and modification of LC3-II/p62(SQSTM1) ratio. Furthermore, by normalizing autophagy markers, CPZ and CMI counteracted the detrimental effects induced by L-BMAA, a neurotoxin mimicking ALS/PDC. Notably, siTPC2 partially reverted CMI- and CPZ-induced neuroprotection as well as that produced by NAADP. At mitochondrial level, these drugs prevented ATP reduction and ROS overproduction in motor neurons exposed to L-BMAA for 24 h. For a longer L-BMAA exposure, CPZ and CMI counteracted LDH, cytochrome C and SMAC/DIABLO release, thus preventing cell demise. These findings suggest that TPC2 activation by drug repurposing could provide novel therapeutic options for ALS via autophagy regulation.}, } @article {pmid40795649, year = {2025}, author = {Rabbani, G and Alif, SM and Zhou, Z and Ryan, J and Karim, N}, title = {Association between higher serum uric acid levels and cognitive function: a systematic review and meta-analysis.}, journal = {The journals of gerontology. Series A, Biological sciences and medical sciences}, volume = {}, number = {}, pages = {}, doi = {10.1093/gerona/glaf174}, pmid = {40795649}, issn = {1758-535X}, abstract = {BACKGROUND: Serum uric acid (SUA) levels may be associated with cognitive function, but findings have been inconsistent, potentially varying by cognitive domain and sex. We aimed to determine the association of SUA and different domains of cognitive function.

METHODS: Five electronic databases were searched to identify relevant peer-reviewed articles. Studies investigating the association between SUA levels and cognitive function were included. Standardised mean difference (SMD) was calculated and separate meta-analyses were conducted for each of the domains. Risk of bias was assessed using the Newcastle-Ottawa Quality Assessment Scale. Between-study heterogeneity was investigated through subgroup analysis and a meta-regression model using study-level covariates.

RESULTS: Ten prospective cohort and sixteen cross-sectional studies were eligible for inclusion, but only a subset of these studies was included in each meta-analysis. Pooled estimates from cross-sectional studies showed that higher SUA levels were significantly associated with better global cognition (n = 6, SMD = 2.27, 95%CI:1.18-3.35), and learning and memory (n = 4, SMD = 1.49, 95%CI:1.12-1.87). Sensitivity analysis, excluding the study conducted on amyotrophic lateral sclerosis (ALS) patients, resulted in better performance estimates for executive function (n = 4, SMD = 0.51, 95%CI:0.47-0.55) and language (n = 2, SMD = 0.75, 95%CI:0.71-0.79). The pooled result from two prospective cohort studies found a positive relationship between SUA levels and attention (SMD = 0.22, 95%CI:0.07-0.36). SUA levels were associated with executive function and learning and memory in males, and with language in females.

CONCLUSIONS: Higher SUA levels were associated with better global cognitive performance executive function, learning and memory, attention and language. These findings highlight low SUA levels as a potential useful biomarker for cognitive decline.}, } @article {pmid40795306, year = {2025}, author = {Guo, J and Zou, Q and Xu, J and Lei, J and Yin, X and Li, B and Fu, J and Mi, J and Wang, Y and Huang, H and Zhang, CY and Chen, X}, title = {In vivo self-assembled SOD1-siRNAs mitigate muscle atrophy and denervation in amyotrophic lateral sclerosis.}, journal = {Brain : a journal of neurology}, volume = {}, number = {}, pages = {}, doi = {10.1093/brain/awaf291}, pmid = {40795306}, issn = {1460-2156}, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by the death of both upper and lower motor neurons. Approximately 20% of familial ALS cases are associated with mutations in the superoxide dismutase type 1 (SOD1) gene. Developing a specific strategy to characteristically silence the pathogenic SOD1 gene remains a crucial goal amidst significant challenges. In this study, we developed a synthetic biology strategy to reprogram the liver as a tissue chassis for the in vivo self-assembly of small extracellular vesicles (sEVs)-encapsulated SOD1-siRNA, aiming to target spinal neurons and silence mutant SOD1 specifically in Tg(SOD1G93A) transgenic mice. We designed a CMV promoter-directed synthetic construct to encode a SOD1-siRNA along with a neuron-targeting rabies virus glycoprotein (RVG) tagged on sEV surface. Theoretically, upon liver uptake, this construct reprograms liver cells to generate and self-assemble SOD1-siRNAs into RVG-tagged sEVs. Subsequently, the sEV-encapsulated SOD1-siRNAs are transported via the endogenous sEV circulation and guided by the RVG tag to the spinal neurons. Experimental results illustrated that intravenous administration of this synthetic construct effectively facilitated in vivo self-assembly of SOD1-siRNAs into circulating sEVs. The functional delivery of SOD1-siRNAs to the spinal cord and cerebral cortex was confirmed through in vivo tracking of sEVs and sEV-encapsulated siRNAs. Treatment of Tg(SOD1G93A) transgenic mice with this construct significantly reduced mutant SOD1 protein levels in the spinal cord and cerebral cortex. Consequently, the characteristic symptoms of ALS, including decreased body weight, shortened lifespan, compromised motor function, muscle atrophy, neuroinflammation, motor neuron loss, and neuromuscular junction degeneration, were substantially ameliorated by the synthetic construct. Furthermore, an AAV-based strategy was devised for the enduring self-assembly of sEV-encapsulated SOD1-siRNA, whereby a single injection led to substantial and sustained inhibition of mutant SOD1 and significant symptom amelioration in transgenic mice. Overall, this study established an effective and convenient therapeutic approach for mitigating muscle atrophy and denervation in animal model, presenting a promising solution for future ALS treatment.}, } @article {pmid40794569, year = {2025}, author = {Benatar, M and Staffaroni, AM and Wuu, J and McDermott, MP and Quintana, M and Swidler, J and Andersen, G and Huey, ED and Turner, MR and Macklin, EA and Berry, JD and McMillan, CT and Gendron, T and Onyike, C and Rosen, H and Heuer, HW and Grignon, AL and Dave, KD and Balas, C and Gleixner, A and Satlin, A and Dunn, B and Dacks, P and Boxer, AL}, title = {Design considerations for C9orf72 disease prevention trials.}, journal = {Brain : a journal of neurology}, volume = {}, number = {}, pages = {}, doi = {10.1093/brain/awaf290}, pmid = {40794569}, issn = {1460-2156}, abstract = {The idea that it might be possible to prevent some forms of amyotrophic lateral sclerosis and frontotemporal dementia has finally come of age. The hexanucleotide repeat expansion in the C9orf72 gene accounts for ∼10% of all amyotrophic lateral sclerosis and 10-15% of all frontotemporal dementia diagnoses, with the two clinical syndromes co-manifesting in a significant number of patients. As a result, clinically unaffected carriers of pathogenic C9orf72 repeat expansions are currently the largest identifiable population at significantly elevated risk for both amyotrophic lateral sclerosis and frontotemporal dementia, and in whom it might be possible to prevent the emergence of clinically manifest disease. Strategies for the design of disease prevention trials among clinically unaffected C9orf72 carriers have begun to emerge separately in the amyotrophic lateral sclerosis and frontotemporal dementia fields. However, recognition of the need to define neurodegenerative diseases based on biology underscores the need to consider all potential clinical manifestations of a C9orf72 repeat expansion together, rather than the traditional siloed approach of focusing on only amyotrophic lateral sclerosis or only frontotemporal dementia. Indeed, emerging clinical and biological markers that might be used to quantify pre-symptomatic disease progression and to predict the short-term risk of phenoconversion to clinically manifest disease are shared across the phenotypic spectrum. Given the anticipated progress in the development of therapeutic strategies to target the C9orf72 repeat expansion, and the enthusiasm for prevention trials among the unaffected C9orf72 repeat expansion carrier population, now is the time to begin work on the design of disease prevention trials. To this end, The Association for Frontotemporal Degeneration and the ALS Association supported a multi-stakeholder workshop (in Washington D.C., June 2024) to unify efforts to design a prevention trial for the population at elevated genetic risk for the phenotypic spectrum of C9orf72 disease. Here we describe recommendations emanating from this Workshop for the selection of outcome measures, delineation of eligibility criteria, optimal use of biomarkers and digital health technologies, potential analytic frameworks, and relevant regulatory considerations related to C9orf72 disease prevention trials. We also emphasize the importance of the amyotrophic lateral sclerosis and frontotemporal dementia communities working together in partnership with the C9orf72 repeat expansion carrier community, the regulatory authorities, and the broader drug development community.}, } @article {pmid40792523, year = {2025}, author = {Duan, QQ and Su, WM and Gu, XJ and Long, J and Jiang, Z and Yin, KF and Cai, WC and Cao, B and Chi, LY and Gao, X and Li, JR and Chen, YP}, title = {Genetically Predict Diet-derived Antioxidants and Risk of Neurodegenerative Diseases Among Individuals of European Descent: A Mendelian Randomization Study.}, journal = {Brain and behavior}, volume = {15}, number = {8}, pages = {e70766}, pmid = {40792523}, issn = {2162-3279}, support = {2022NSFSC0749//The National Natural Science Fund of Sichuan/ ; 2022YFC2703101//National Key Research and Development Program of China/ ; 2023YFS0269//The Science and Technology Bureau Fund of Sichuan Province/ ; }, mesh = {Female ; Humans ; Male ; Amyotrophic Lateral Sclerosis/genetics ; *Antioxidants/metabolism ; Diet ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Mendelian Randomization Analysis ; *Neurodegenerative Diseases/genetics ; Parkinson Disease/genetics ; Polymorphism, Single Nucleotide ; *White People/genetics ; }, abstract = {BACKGROUND: The incidence of neurodegenerative disorders (NDDs) is increasing, and currently, there are no curative treatments available for these conditions. The potential benefits of supplementation with diet-derived antioxidants and their metabolites for NDDs remain a subject of debate. In this study, we employed a two-sample Mendelian randomization (MR) analysis to investigate the potential causal relationship between elevated circulating antioxidant levels and the risk of NDDs.

METHODS: We used single-nucleotide polymorphisms (SNPs) related to diet-derived antioxidants and p < 1E-05 as instrumental variables (IVs). The NDDs we studied included Parkinson's disease (PD) (33,674 cases and 449,056 controls), Alzeimers disease (AD) (111,326 cases and 677,663 controls), amyotrophic lateral sclerosis (ALS) (27,205 cases and 110,881 controls), and frontotemporal dementia (FTD) (3526 cases and 9402 controls) from GWASs conducted in the European descent. Two-sample MR was performed together with a series of sensitivity analyses. The main statistical analyses were conducted using the package "TwoSampleMR (V.0.5.6)" in R (V.4.2.0).

RESULTS: Genetically predicted levels of α-tocopherol and carotene were found to be associated with a reduced risk of ALS, with odds ratios (OR) of 0.45 (95% confidence interval [CI]: 0.31, 0.66; p = 3.97 × 10^-5) and 0.82 (95% CI: 0.68, 0.99; p = 0.0427), respectively. Similarly, vitamin E (OR 0.70; [95% CI 0.50, 0.98]; p  = 0.0358) and ascorbate (OR 0.85; [95% CI: 0.73, 0.98]; p = 0.0216) demonstrated a protective effect against PD. Furthermore, elevated levels of retinol were associated with a reduced incidence of FTD, with an OR of 0.92 (95% CI: 0.86, 0.99; p = 0.0196), although they were also linked to an increased risk of ALS (OR 1.02 [95% CI 1.01, 1.04], p = 0.0017) and PD (OR 1.06 [95% CI 1.02, 1.09], p = 0.0121). No significant causal association was observed between circulating antioxidants and AD.

CONCLUSION: This MR study indicated a potential protective effect of α-tocopherol and carotene on ALS, vitamin E and ascorbate on PD, and retinol on FTD, while also identifying retinol as a risk factor for ALS and PD. These findings could contribute to the exploration of dietary therapies for NDDs. Further research is necessary to substantiate the potential associations between diet-derived antioxidants or their metabolites and the risk of NDDs in individuals.}, } @article {pmid40791706, year = {2025}, author = {Spencer, BE and Irwin, DJ and Van Deerlin, VM and Suh, E and Lee, EB and Elman, L and Quinn, CC and Amado, D and Baer, M and Grossman, M and Wolk, DA and McMillan, CT}, title = {Polygenic associations with clinical and neuropathological trait heterogeneity across TDP-43 proteinopathies.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, doi = {10.1101/2023.10.05.23296613}, pmid = {40791706}, abstract = {OBJECTIVE: TDP-43 proteinopathies, including amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration with TDP-43 (FTLD-TDP), and limbic-predominant age-related TDP-43 encephalopathy, encompass a spectrum of clinical and neuropathological traits. Despite mounting evidence for shared genetic risk across TDP-43 proteinopathies, the modifiers of individual-level traits are unknown. We aimed to identify polygenic contributions to trait heterogeneity across TDP-43 proteinopathies.

METHODS: We used weighted correlation analysis of GWAS summary statistics for ALS, FTLD-TDP, and hippocampal sclerosis of aging (HS-Aging) to identify data-driven clusters of highly correlated single nucleotide polymorphisms (SNPs). We performed gene ontology enrichment analysis for each identified cluster. We derived cluster-specific polygenic scores and evaluated their association with clinical and neuropathological traits in an independently evaluated sample of individuals who met neuropathological and/or genetic criteria for FTLD-TDP or ALS (n=260).

RESULTS: We identified 5 distinct data-driven clusters, including 3 GWAS phenotype-specific clusters (FTLD-TDP, ALS, HS-Aging) and 2 clusters representing the overlap between a pair of GWAS phenotypes (ALS-FTLD and FTLD-HS). Pathway analysis revealed biologically meaningful associations including distinct GWAS phenotype-specific processes within clusters. Cluster-specific ALS and FTLD-TDP polygenic risk each associated with individual-level clinical traits, even within the context of autosomal dominant mutation carriers, where higher ALS polygenic risk associated with neuromuscular impairment and higher FTLD-TDP polygenic risk associated with cognitive-behavioral impairment. Moreover, higher FTLD-TDP polygenic risk associated with higher TDP-43 burden within characteristic FTLD-TDP brain regions.

INTERPRETATION: We suggest that there are polygenic modifiers of clinical and neuropathological traits across TDP-43 proteinopathies that may contribute to individual-level differences, including likelihood for developing FTLD or ALS.}, } @article {pmid40790269, year = {2025}, author = {Yang, S and Wijegunawardana, D and Sheth, U and Veire, AM and Salgado, JMS and Arab, T and Agrawal, M and Zhou, J and Pereira, JD and Gendron, TF and Guo, JU}, title = {Aberrant splicing exonizes C9orf72 repeat expansion in ALS/FTD.}, journal = {Nature neuroscience}, volume = {}, number = {}, pages = {}, pmid = {40790269}, issn = {1546-1726}, support = {R35 GM152208/GM/NIGMS NIH HHS/United States ; DP2 GM132930/GM/NIGMS NIH HHS/United States ; T32 NS041228/NS/NINDS NIH HHS/United States ; T32 NS041228/NS/NINDS NIH HHS/United States ; P30 AG066508/AG/NIA NIH HHS/United States ; P30 AG066508/AG/NIA NIH HHS/United States ; P30 AG066508/AG/NIA NIH HHS/United States ; P30 AG066508/AG/NIA NIH HHS/United States ; }, abstract = {A nucleotide repeat expansion (NRE) (GGGGCC)n within the first annotated intron of the C9orf72 (C9) gene is a common cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). While previous studies have shown that C9 NRE produces several toxic dipeptide repeat (DPR) proteins, the mechanism by which an intronic RNA segment can access the cytoplasmic translation machinery remains unclear. By selectively capturing and sequencing NRE-containing RNAs (NRE-capture-seq) from patient-derived fibroblasts and neurons, we found that, in contrast to previous models, C9 NRE is retained as part of an extended exon 1 due to the usage of various downstream alternative 5' splice sites. These aberrant splice isoforms accumulate in C9-ALS/FTD brains, and their production is promoted by serine/arginine-rich splicing factor 1 (SRSF1). Antisense oligonucleotides targeting either SRSF1 or the aberrant C9 splice isoforms reduced the levels of DPR. Together, our findings revealed a crucial role of aberrant splicing in the biogenesis of NRE-containing RNAs and demonstrated potential therapeutic strategies to target these pathogenic transcripts.}, } @article {pmid40789150, year = {2025}, author = {Roy, D and Dashora, C and Patel, AB}, title = {Excitatory and Inhibitory Activity Is Differentially Affected in SOD1[G37R] Mouse Model of ALS: A [1]H-[[13]C]-NMR Analysis.}, journal = {ACS chemical neuroscience}, volume = {}, number = {}, pages = {}, doi = {10.1021/acschemneuro.5c00208}, pmid = {40789150}, issn = {1948-7193}, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder marked by the selective degeneration of motor neurons in the central nervous system. In this study, neuronal and astroglial metabolic activities were evaluated in the cerebral cortex and spinal cord of an 18 month-old male SOD1[G37R] mouse model of ALS using [1]H-[[13]C]-nuclear magnetic resonance spectroscopy in tissue extracts in conjunction with an infusion of [1,6-[13]C2]glucose or [2-[13]C]acetate, respectively. The cerebral metabolic fluxes were obtained by fitting a three-compartment metabolic model to the [13]C turnover of amino acids from [13]C-glucose. The SOD1[G37R] mice exhibited decreased forelimb strength and hindlimb function compared to age-matched controls. The spinal cord of SOD1[G37R] mice exhibited a reduction in aspartate, glutamate, N-acetylaspartate, and N-acetylaspartylglutamate levels and an increase in myo-inositol, glutamine, and taurine levels. The increased acetate oxidation rate suggests heightened inflammatory conditions in the cerebral cortex and spinal cord of SOD1[G37R] mice. The glutamatergic and GABAergic TCA cycle and neurotransmitter cycle fluxes were reduced in the spinal cord of SOD1[G37R] mice. In contrast, glutamatergic fluxes were increased in the cerebral cortex. These data suggest heightened excitatory activity in the cerebral cortex and differential degeneration of excitatory and inhibitory neurons in the spinal cord in advanced conditions of ALS.}, } @article {pmid40788112, year = {2025}, author = {Guha, A and Si, Y and Smith, R and Singh, BK and Zogu, B and Yadav, A and Smith, KA and Kazamel, M and Jiang, N and Ho, R and Thalacker-Mercer, A and Andrabi, SA and Da Silva Pereira, JDT and Salgado, JS and Agrawal, M and Velic, EH and King, PH}, title = {The myokine FGF21 associates with enhanced survival in ALS and mitigates stress-induced cytotoxicity.}, journal = {Aging}, volume = {17}, number = {}, pages = {}, doi = {10.18632/aging.206298}, pmid = {40788112}, issn = {1945-4589}, abstract = {Amyotrophic lateral sclerosis (ALS) is an age-related and fatal neurodegenerative disease characterized by progressive muscle weakness. There is marked heterogeneity in clinical presentation, progression, and pathophysiology with only modest treatments to slow disease progression. Molecular markers that provide insight into this heterogeneity are crucial for clinical management and identification of new therapeutic targets. In a prior muscle miRNA sequencing investigation, we identified altered FGF pathways in ALS muscle, leading us to investigate FGF21. We analyzed human ALS muscle biopsy samples and found a large increase in FGF21 expression with localization to atrophic myofibers and surrounding endomysium. A concomitant increase in FGF21 was detected in ALS spinal cords which correlated with muscle levels. FGF21 was increased in the SOD1[G93A] mouse beginning in presymptomatic stages. In parallel, there was dysregulation of the co-receptor, β-Klotho, with higher levels detected in ALS muscle biopsies and lower levels in post-mortem muscle compared to controls. Plasma FGF21 levels were increased in ALS patients and high levels correlated with slower disease progression, prolonged survival, and increased body mass index. In cellulo, FGF21 was induced in differentiating muscle cells and ectopic treatment with FGF21 enhanced muscle differentiation. Ectopic FGF21 mitigated oxidative stress-induced loss of viability in iPSC-derived ALS motor neurons and muscle cells expressing SOD1[G93A]. In summary, FGF21 is a novel biomarker in ALS which exerts trophic effects in the neuromuscular system.}, } @article {pmid40787400, year = {2025}, author = {Hwang, D and Park, SA and Kim, JH and Lee, SY and Lee, J and Kim, HS and Kim, KA and Lee, SH and Oh, TJ and Lee, J and An, S}, title = {Gold Nanoparticle-mRNA Conjugates Encapsulated in Lipid Nanoparticles for Coordinated Codelivery of Multiple mRNAs.}, journal = {ACS omega}, volume = {10}, number = {30}, pages = {32998-33007}, pmid = {40787400}, issn = {2470-1343}, abstract = {Gold nanoparticles (AuNPs) can be engineered to be utilized as carriers via anchoring multiple nucleic acids, including mRNAs, in specific ratios. However, the negative charge of mRNA-AuNP conjugates presents significant challenges for efficient cellular uptake and subsequent expression. To overcome this limitation, we developed a delivery system that combines mRNA-AuNP conjugation with lipid nanoparticles (LNPs) to enhance intracellular delivery. In our approach, AuNPs were functionalized with a thiolated antisense leader sequence (ALS), oligonucleotides complementary to the 5'-end leader sequence of the 5'-untranslated region (UTR) of the mRNA. This functionalization resulted in the formation of mRNA-ALS-AuNP conjugates, which were then encapsulated within LNPs. When we compared the ALS-AuNP@LNP constructs to ALS-AuNPs alone, ALS-AuNP@LNP demonstrated superior delivery and expression of enhanced green fluorescence protein (EGFP) mRNA across multiple cell lines, as evidenced by robust green fluorescence. Furthermore, this system enables the precise codelivery of multiple mRNAs in defined ratios, as demonstrated by the successful codelivery of EGFP and mCherry mRNAs. These findings highlight the potential of the mRNA-ALS-AuNP@LNP platform as an effective and versatile tool for advancing mRNA-based therapeutics and vaccine development.}, } @article {pmid40785665, year = {2025}, author = {Plaitano, EG and Pate, BL and Ryan, KM}, title = {Teaching Emergency Medical Technicians about Advanced Life Support Interventions: Pilot Study of an Online Continuing Education Course.}, journal = {Disaster medicine and public health preparedness}, volume = {19}, number = {}, pages = {e233}, doi = {10.1017/dmp.2025.10171}, pmid = {40785665}, issn = {1938-744X}, support = {F31 DA062393/DA/NIDA NIH HHS/United States ; }, mesh = {Humans ; Pilot Projects ; *Emergency Medical Technicians/education ; Surveys and Questionnaires ; *Education, Continuing/methods/standards ; *Education, Distance/methods ; Male ; Female ; *Teaching/standards/statistics & numerical data ; Adult ; Educational Measurement/methods ; Clinical Competence/standards ; }, abstract = {OBJECTIVES: Emergency Medical Technician (EMT) scope of practice guidelines in the US suggest that EMTs should assist paramedics with advanced skills during patient care. However, learning to assist with these skills is not an EMT national education requirement. This study examined the feasibility and impact of a short, online pilot continuing education course in providing EMTs with the confidence and basic knowledge to assist with advanced interventions.

METHODS: The pilot cohort included licensed EMTs (n=10) self-enrolled in a continuing education class listed on the institution's EMS continuing education website and advertised on social media. Optional, anonymous questionnaires and multiple-choice exams were administered to students pre/post-course. Statistical analysis included paired nonparametric tests.

RESULTS: Total scores were 43% higher on the post-exam (88/100, 95% CI [76, 100]) compared to the pre-exam (45/100, 95% CI [37, 53]) (P<0.05). Self-reported comfort was higher on the post-evaluation for needle thoracostomy (95% increase), advanced airways (25% increase), EKGs (19% increase), intravenous access (14% increase), and communication (22% increase).

CONCLUSIONS: Results suggest that short, online continuing education courses on BLS-ALS interface for EMTs might be efficacious in improving both comfort and knowledge of selected advanced interventions often used by paramedics, although larger future studies are needed.}, } @article {pmid40785560, year = {2025}, author = {Glas, G}, title = {[De psychiater als activist].}, journal = {Tijdschrift voor psychiatrie}, volume = {67}, number = {6}, pages = {319-320}, pmid = {40785560}, issn = {0303-7339}, } @article {pmid40784657, year = {2025}, author = {Babcock, KJ and Abdolmohammadi, B and McKee, AC}, title = {Recent Advances in Chronic Traumatic Encephalopathy.}, journal = {The American journal of pathology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ajpath.2025.07.008}, pmid = {40784657}, issn = {1525-2191}, abstract = {Exposure to repeated head impacts (RHI), such as those experienced in contact sports or military service, can lead to the development of chronic traumatic encephalopathy (CTE), a neurodegenerative tauopathy. CTE cannot be diagnosed during life, only by post-mortem neuropathological exam. The pathognomonic lesion of CTE consists of a perivascular accumulation of hyperphosphorylated tau (p-tau) as neurofibrillary tangles and dotlike neurites, preferentially at the depths of cortical sulci. The biomechanics of RHI involve acceleration, deceleration, and rotational forces that distort brain tissue and strain fragile structures such as blood vessels and axons, especially in the crevices of the brain where these forces are localized. CTE is unique from other tauopathies in its molecular structure, pattern, and regional distribution of tau. Studies in American football, rugby, and ice hockey players demonstrate a dose-response relationship between years of exposure to sport and increased CTE risk and severity. The clinical symptoms associated with CTE are classified as Traumatic Encephalopathy Syndrome (TES). Exposure to RHI also increases the deposition of other pathological proteins, including beta-amyloid, alpha-synuclein, and TDP-43, raising the risk for other neurodegenerations such as Alzheimer's disease (AD), Lewy body disease (LBD), frontotemporal lobar degeneration (FTLD), and amyotrophic lateral sclerosis (ALS).}, } @article {pmid40784541, year = {2025}, author = {Haidar, M and Viden, A and Daniel, C and Cuic, B and Wang, T and Rosier, M and Tomas, D and Mills, SA and Govier-Cole, A and Djouma, E and Perera, ND and Luikinga, S and Rytova, V and Barton, SK and Gonsalvez, DG and Palmer, LM and McLean, C and Kiernan, MC and Vucic, S and Turner, BJ}, title = {Cortical hyperexcitability drives dying forward amyotrophic lateral sclerosis symptoms and pathology in mice.}, journal = {Progress in neurobiology}, volume = {252}, number = {}, pages = {102809}, doi = {10.1016/j.pneurobio.2025.102809}, pmid = {40784541}, issn = {1873-5118}, abstract = {Degeneration of both upper motor neurons in the brain and lower motor neurons in the spinal cord defines amyotrophic lateral sclerosis (ALS), but how they are linked in ALS pathophysiology is unclear. Here, we uncover a cortical origin of neurodegeneration in ALS mediated by upper motor neuron hyperexcitability. Chronic hyperexcitability of upper motor neurons induced by excitatory chemogenetics in healthy adult mice induced progressive motor deficits, weakness and core pathological hallmarks of ALS, including upper motor neurons loss, synaptic pathology, corticospinal tract degeneration and reactive gliosis. Importantly, upper motor neuron hyperexcitability and loss were sufficient to drive degeneration of lower motor neurons and their distal axons and neuromuscular junctions, associated with astrocyte and microglial activation in spinal cord. Cortical hyperexcitability also triggered cytoplasmic TAR DNA binding protein 43 (TDP-43) aggregation in upper motor neurons and lower motor neurons, placing hyperexcitability upstream of TDP-43 proteinopathy in ALS. These findings establish a cortical origin of ALS mediated by upper motor neurons, consistent with an anterograde mechanism of neurodegeneration throughout the central and peripheral nervous systems.}, } @article {pmid40783639, year = {2025}, author = {Lin, CY and Nelson, A and Lee, W and Feng, Z and Lee, YS}, title = {Characterization of lower urinary tract dysfunction in a mouse model of amyotrophic lateral sclerosis.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {29190}, pmid = {40783639}, issn = {2045-2322}, support = {2022-040//Cleveland Clinic Technology Development Investment Project and Ohio Third Frontier Technology Validation and Start-up Fund/ ; }, mesh = {Animals ; *Amyotrophic Lateral Sclerosis/physiopathology/complications/genetics ; Disease Models, Animal ; Mice ; Female ; Male ; Mice, Transgenic ; Superoxide Dismutase-1/genetics ; Electromyography ; Urodynamics ; Urethra/physiopathology ; *Lower Urinary Tract Symptoms/physiopathology/etiology ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is characterized by a progressive loss of motor function due to degeneration of motor neurons. In addition to motor-related symptoms, increasing evidence from clinical studies indicate lower urinary tract (LUT) dysfunctions (urge incontinence) are found in patients with ALS, which causes a significant negative impact on quality of life. However, it remains unclear whether LUT dysfunction can be validated in preclinical ALS models. Here, we attempt to answer this question by using comprehensive urodynamic testing with electromyogram of external urethral sphincter (EUS) activity in both female and male SOD1-G93A ALS mice at both 9 weeks of age (pre-onset stage) and 16 weeks of age (early symptomatic stage). Our results demonstrate that the detrusor muscle is hyperactive, voiding volume is decreased, and the EUS relaxation period is shorter in female and male SOD1-G93A ALS mice at both 9 weeks and 16 weeks of age, compared to age-matched wild-type animals. The symptoms of urge incontinence found in the current study are similar to the clinical findings, indicating that SOD1-G93A ALS mice can be used as a preclinical model to develop therapeutics for ALS patients with LUT dysfunction.}, } @article {pmid40783546, year = {2025}, author = {Du, M and Akerman, SC and Fare, CM and Ruan, L and Vidensky, S and Mamedova, L and Koo, K and Lee, J and Rothstein, JD}, title = {Divergent and convergent TMEM106B pathology in murine models of neurodegeneration and human disease.}, journal = {Acta neuropathologica communications}, volume = {13}, number = {1}, pages = {169}, pmid = {40783546}, issn = {2051-5960}, support = {R35NS132179/NH/NIH HHS/United States ; HT94252310136//U.S. Department of Defense/ ; }, mesh = {Animals ; Humans ; *Membrane Proteins/metabolism/genetics ; Disease Models, Animal ; *Nerve Tissue Proteins/metabolism/genetics ; Mice ; *Frontotemporal Dementia/pathology/metabolism/genetics ; *Amyotrophic Lateral Sclerosis/pathology/metabolism/genetics ; *Brain/pathology/metabolism ; Mice, Transgenic ; *Neurodegenerative Diseases/pathology/metabolism ; *Tauopathies/pathology/metabolism ; Male ; Female ; }, abstract = {TMEM106B is a lysosome/late endosome protein that is a potent genetic modifier of multiple neurodegenerative diseases as well as general aging. Recently, TMEM106B was shown to form insoluble aggregates in postmortem human brain tissue, drawing attention to TMEM106B pathology and the potential role of TMEM106B aggregation in disease. In the context of neurodegenerative diseases, TMEM106B has been studied in vivo using animal models of neurodegeneration, but these studies rely on overexpression or knockdown approaches. To date, endogenous TMEM106B pathology and its relationship to known canonical pathology in animal models has not been reported. Here, we analyze histological patterns of the endogenous TMEM106B protein in murine models of C9ORF72-related amyotrophic lateral sclerosis and frontotemporal dementia (C9-ALS/FTD), SOD1-related ALS, and tauopathy using an extensively validated TMEM106B antibody. We found profound correlations between the endogenous TMEM106B protein with known TDP-43 and tau pathology in murine models of C9-ALS/FTD and tauopathy, respectively. By using an antibody previously shown to recognize the pathologic TMEM106B C-terminal fragments, we then performed a similar analysis on postmortem brain tissues from patients with C9-ALS/FTD, Alzheimer's disease (AD), and AD with limbic-predominant age-related TDP-43 encephalopathy (AD/LATE). Convergent evidence from both murine models and human patients links TMEM106B to TDP-43 nuclear clearance at the cellular level in C9-ALS. By characterizing endogenous TMEM106B in mice and human postmortem tissue, our work reveals essential considerations that must be taken when analyzing data from in vivo mouse studies and elucidates new insights supporting the involvement of TMEM106B in the pathogenesis and progression of multiple neurodegenerative diseases.}, } @article {pmid40783116, year = {2025}, author = {Chang, JW and Wang, F}, title = {Response to Goleva et al., "Response to Chang et al's 'Abrocitinib versus dupilumab: impact on skin barrier function and proteomics in atopic dermatitis'".}, journal = {Journal of the American Academy of Dermatology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jaad.2025.07.063}, pmid = {40783116}, issn = {1097-6787}, } @article {pmid40782358, year = {2025}, author = {St Clair-Sullivan, N and Brighton, LJ and Jha, P and Bone, AE and Sudirman, NA and Maddocks, M and Bayly, J}, title = {Assistive technologies for people with advanced disease and in palliative care: a scoping review.}, journal = {Disability and rehabilitation. Assistive technology}, volume = {}, number = {}, pages = {1-17}, doi = {10.1080/17483107.2025.2536175}, pmid = {40782358}, issn = {1748-3115}, abstract = {Population ageing, multi-morbidity and associated disability is shifting global demand for health and care services. Innovative solutions are required to meet the evolving needs of people with advanced disease, support independent functioning and quality of life. This scoping review aimed to map and examine evidence on the role of assistive technology in adults with advanced disease and those receiving palliative care. A systematic search of Medline, Embase, PsychINFO and Cinahl, was conducted from inception to 31[st] July 2024 for studies investigating use of assistive technologies in people with advanced disease or receiving palliative care. Titles and abstracts were independently screened before full texts retrieved for eligibility review, data extraction, synthesis and descriptive analysis. 23/811 screened papers met eligibility criteria. Participants included ALS/MND (n13/23); palliative care (n4/23); cancer (n2/23); dementia (n2/23); Parkinson's (n1/23) and frailty (n1/23). Studies evaluated assistive technologies supporting ten functional domains; most frequently to support communication and information management (n13/23), least frequently orthoses and prosthesis, and domestic activities and participation in domestic life (n1/23). Outcomes of assistive technology use related to functioning, quality of life, dignity in end-of-life care and health service use. Implications for individual users, device design and delivery are discussed. This review highlights potential benefits of assistive technologies and gaps in research on their use for adults with advanced disease or receiving palliative care. Empirical evidence is limited and focuses on communication enhancing high-tech devices. Future research should explore assistive technology's impact over time on health outcomes, alongside strategies to integrate provision in care.}, } @article {pmid40781905, year = {2025}, author = {Steffke, C and Baskar, K and Bachhuber, F and Wiesenfarth, M and Dorst, J and Schuster, J and Schöberl, F and Reilich, P and Regensburger, M and German, A and Günther, R and Vidovic, M and Petri, S and Meyer, T and Hagenacker, T and Grosskreutz, J and Weyen, U and Weydt, P and Haarmeier, T and Lingor, P and Wolf, J and Hermann, A and Prudlo, J and Günther, K and Knehr, A and Elmas, Z and Uzelac, Z and Witzel, S and Ruf, WP and Freischmidt, A and Ho, R and Ludolph, AC and Weishaupt, JH and Tumani, H and Oeckl, P and Brenner, D and Catanese, A}, title = {Targeted Proteomics upon Treatment with Tofersen Identifies Novel Response Markers for Superoxide Dismutase 1-Linked Amyotrophic Lateral Sclerosis.}, journal = {Annals of neurology}, volume = {}, number = {}, pages = {}, doi = {10.1002/ana.70025}, pmid = {40781905}, issn = {1531-8249}, support = {SFB 1506//Deutsche Forschungsgemeinschaft/ ; Ca2/1//Deutsche Gesellschaft für Muskelkranke/ ; AlamarNeurologyGrant//Alamar Biosciences/ ; Exzellenzstipendium2022_EKES.18//Else Kröner-Fresenius-Stiftung/ ; }, abstract = {OBJECTIVE: Tofersen is the first effective and approved therapy for superoxide dismutase 1 (SOD1)-associated amyotrophic lateral sclerosis (ALS [SOD1-ALS]). Following treatment with tofersen, neurofilament levels in patients' cerebrospinal fluid (CSF) and serum seem to respond earlier than clinical parameters. This evidence prompted us to hypothesize that this novel treatment could provide an opportunity to identify additional biomarkers responsive to therapy in SOD1-ALS.

METHODS: We investigated a panel of 120 neural, glial, and inflammatory markers in CSF and serum samples longitudinally collected from a total of 28 SOD1-ALS patients at baseline, and after 3, 6 and 12 months of treatment with tofersen, followed by validation with conventional methodology.

RESULTS: We identified a set of proteins, including neurofilament light chain, neurofilament heavy chain, amyloid-beta 1-40 and amyloid-beta 1-42, neuropeptide Y (NPY), and ubiquitin C-terminal hydrolase L1 (UCHL1), whose CSF levels both differed between SOD1-ALS and the control group, and were responsive to tofersen at 3 and 6 months after treatment initiation. Another group of markers, including the neuropentraxin (NPTX) family members NPTX1, NPTX2 and NPTXR, did not separate untreated SOD1-ALS from controls, but was responsive to tofersen. At 12 months on tofersen the levels of neurofilament light chain, neurofilament heavy chain, NPTX1, NPTX2, and NPTXR remained reduced compared with baseline, and correlated with the clinical response to tofersen. Consistent with increasing CSF pleocytosis and intrathecal immunoglobulin production, inflammatory markers were significantly increased after 12 months of treatment.

INTERPRETATION: Our results highlight a complex, time-dependent differential response of CSF biomarkers to tofersen treatment, and may pave the way for developing a panel of responsive proteins to make biomarker endpoints more robust in clinical trials for SOD1-ALS and beyond. ANN NEUROL 2025.}, } @article {pmid40780661, year = {2025}, author = {Goleva, E and Berdyshev, E and Kreimer, S and Leung, DYM}, title = {Response to Chang et al's "Abrocitinib versus dupilumab: impact on skin barrier function and proteomics in atopic dermatitis".}, journal = {Journal of the American Academy of Dermatology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jaad.2025.05.1462}, pmid = {40780661}, issn = {1097-6787}, } @article {pmid40779613, year = {2025}, author = {Chaouch, A and Crook, A and Douglas, AGL and McDermott, CJ and Al-Chalabi, A and McNeill, A and Bedford, J and Howard, J and MacLeod, R}, title = {The use of genetic testing in amyotrophic lateral sclerosis (ALS): a practical approach.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {}, number = {}, pages = {1-7}, doi = {10.1080/21678421.2025.2539895}, pmid = {40779613}, issn = {2167-9223}, abstract = {Amyotrophic lateral sclerosis (ALS) is a rare and fatal neurodegenerative disease thought to be precipitated by genetic, environment and lifestyle factors. In the UK, whole genome sequencing has become available to all people living with ALS, regardless of their family history or age of onset of disease. However, there is currently no formal guidance on how to deliver genetic counseling and testing in busy mainstream clinics. This article offers practical suggestions to clinicians who may wish or need to discuss genomic testing. As more clinical trials and targeted gene therapies develop, it is likely that conversations will evolve, reflecting the dynamic nature of this important and complex field.}, } @article {pmid40779173, year = {2025}, author = {Gil Chong, P and Mazon, M and Cerdá-Alberich, L and Beser Robles, M and Carot, JM and Vázquez-Costa, JF and Martí-Bonmatí, L}, title = {Machine learning diagnostic model for amyotrophic lateral sclerosis analysis using MRI-derived features.}, journal = {Neuroradiology}, volume = {}, number = {}, pages = {}, pmid = {40779173}, issn = {1432-1920}, abstract = {PURPOSE: Amyotrophic Lateral Sclerosis is a devastating motor neuron disease characterized by its diagnostic difficulty. Currently, no reliable biomarkers exist in the diagnosis process. In this scenario, our purpose is the application of machine learning algorithms to imaging MRI-derived variables for the development of diagnostic models that facilitate and shorten the process.

METHODS: A dataset of 211 patients (114 ALS, 45 mimic, 22 genetic carriers and 30 control) with MRI-derived features of volumetry, cortical thickness and local iron (via T2* mapping, and visual assessment of susceptibility imaging). A binary classification task approach has been taken to classify patients with and without ALS. A sequential modeling methodology, understood from an iterative improvement perspective, has been followed, analyzing each group's performance separately to adequately improve modelling. Feature filtering techniques, dimensionality reduction techniques (PCA, kernel PCA), oversampling techniques (SMOTE, ADASYN) and classification techniques (logistic regression, LASSO, Ridge, ElasticNet, Support Vector Classifier, K-neighbors, random forest) were included. Three subsets of available data have been used for each proposed architecture: a subset containing automatic retrieval MRI-derived data, a subset containing the variables from the visual analysis of the susceptibility imaging and a subset containing all features.

RESULTS: The best results have been attained with all the available data through a voting classifier composed of five different classifiers: accuracy = 0.896, AUC = 0.929, sensitivity = 0.886, specificity = 0.929.

CONCLUSION: These results confirm the potential of ML techniques applied to imaging variables of volumetry, cortical thickness, and local iron for the development of diagnostic model as a clinical tool for decision-making support.}, } @article {pmid40778857, year = {2025}, author = {Hasegawa-Ogawa, M and Onda-Ohto, A and Nakajo, T and Funabashi, A and Ohya, A and Yazaki, R and Okano, HJ}, title = {Dominant-negative isoform of TDP-43 is regulated by ALS-linked RNA-binding proteins.}, journal = {The Journal of cell biology}, volume = {224}, number = {10}, pages = {}, pmid = {40778857}, issn = {1540-8140}, support = {JP16H07218//Japan Society for the Promotion of Science/ ; JP17K09766//Japan Society for the Promotion of Science/ ; JP17K14967//Japan Society for the Promotion of Science/ ; JP20K15904//Japan Society for the Promotion of Science/ ; JP21K07302//Japan Society for the Promotion of Science/ ; JP23K06812//Japan Society for the Promotion of Science/ ; //Uehara Memorial Foundation/ ; //Jikei University Graduate Research Fund/ ; //Jikei University School of Medicine/ ; }, mesh = {*DNA-Binding Proteins/genetics/metabolism ; *Amyotrophic Lateral Sclerosis/metabolism/genetics/pathology ; Humans ; *RNA-Binding Protein FUS/metabolism/genetics ; Protein Isoforms/genetics/metabolism ; Heterogeneous-Nuclear Ribonucleoprotein K/metabolism/genetics ; Heterogeneous-Nuclear Ribonucleoprotein Group A-B/metabolism/genetics ; Heterogeneous Nuclear Ribonucleoprotein A1 ; HEK293 Cells ; Alternative Splicing ; Animals ; *RNA-Binding Proteins/metabolism/genetics ; }, abstract = {TDP-43, an RNA-binding protein (RBP) encoded by the TARDBP gene, is crucial for understanding the pathogenesis of neurodegenerative diseases like amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration. Dysregulated TDP-43 causes motor neuron loss, highlighting the need for proper expression levels. Here, we identify a dominant-negative isoform among the multiple TARDBP splicing variants and validate its endogenous expression using a developed antibody against its translated product. Furthermore, we revealed that ALS-associated RBPs regulate its expression: hnRNP K promotes its splicing and expression, while hnRNP A1 and FUS suppress these processes through distinct mechanisms. hnRNP A1 inhibits hnRNP K-mediated splicing, and FUS represses the dominant-negative isoform through both its translational inhibition and hnRNP K suppression. Notably, ALS-mutant FUS weakens this regulatory mechanism, leading to impaired repression of hnRNP K and the dominant-negative isoform. Our findings suggest a regulatory network involving ALS-linked RBPs that govern TDP-43 isoform expression and provide new insights into how disruptions in this network contribute to ALS pathogenesis.}, } @article {pmid40778304, year = {2025}, author = {Zhang, K and Wen, M and Nan, X and Zhao, S and Li, H and Ai, Y and Zhu, H}, title = {NMDA receptors in neurodegenerative diseases: mechanisms and emerging therapeutic strategies.}, journal = {Frontiers in aging neuroscience}, volume = {17}, number = {}, pages = {1604378}, pmid = {40778304}, issn = {1663-4365}, abstract = {NMDA receptors (NMDARs) are widely distributed throughout the central nervous system (CNS) and play pivotal roles in normal physiological processes such as synaptic plasticity, learning, and memory. Substantial evidence indicates that NMDAR dysfunction, particularly excessive calcium influx, critically contributes to the pathogenesis of major neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS). Dysregulated glutamatergic signaling synergizes with pathological protein aggregation (e.g., Aβ, α-synuclein, mutant huntingtin) to drive neuronal loss. We systematically delineate NMDAR-related mechanisms underlying neurodegeneration, highlighting spatial-specific roles (e.g., synaptic NMDAR-mediated neuroprotection versus extrasynaptic NMDAR-mediated excitotoxicity) and crosstalk with mitochondrial dysfunction and oxidative stress. We critically evaluate current therapeutic strategies targeting NMDARs, including subunit-selective modulators, downstream effector modulation, and glutamate transporter modulation designed to restore NMDAR homeostasis. Consequently, NMDARs and their modulators represent promising therapeutic targets for these refractory conditions. This review comprehensively summarizes current research on the involvement of NMDARs and the glutamatergic system in neurodegenerative diseases. Furthermore, we discuss the clinical application of NMDAR-targeting agents and explore emerging therapeutic strategies focused on modulating NMDAR-related pathways. This article aims to provide a reference for elucidating the molecular mechanisms underlying these neurodegenerative disorders and to highlight potential avenues for future drug development.}, } @article {pmid40777887, year = {2025}, author = {Ek, JE and Wittig, J and Rogers, J and Soar, J and , }, title = {A survey of Advanced Life Support practices in countries implementing the European Resuscitation Council guidelines.}, journal = {Resuscitation plus}, volume = {25}, number = {}, pages = {101032}, pmid = {40777887}, issn = {2666-5204}, abstract = {OBJECTIVE: The 2025 European Resuscitation Council (ERC) Advanced Life Support (ALS) Guidelines writing group aims to produce inclusive guidelines enabling implementation by National Resuscitation Councils (NRC) based on local resources and practices. We aimed to describe ALS practices across NRCs to further inform the 2025 ERC ALS Guidelines.

METHODS: A cross-sectional survey was conducted to assess clinical practices for defibrillation, drugs and airway management during ALS in out-of-hospital cardiac arrest (OHCA) and in-hospital cardiac arrest (IHCA) amongst countries represented by an NRC. NRCs were invited to suggest practices for consideration in the 2025 ERC ALS Guidelines.

RESULTS: Among 31 NRCs, 30 (96.8 %) provided data. Defibrillation pads were used for OHCA in 21 (70 %) and for IHCA in 15 (50 %) of countries, while paddles were reported by 3 (10 %) and 6 (20 %) for OHCA and IHCA, respectively. Most NRCs reported not using a pre-charging strategy (23 [76.7 %] OHCA; 26 [86.7 %] IHCA). Amiodarone was the primary antiarrhythmic (26 [89.7 %], OHCA; 28 [93.3 %], IHCA), and adrenaline was the primary vasopressor (27 [90 %], OHCA; 29 [96.7 %], IHCA). Airway management practices varied, 12 (41.4 %) reported supraglottic airway devices as the primary choice for OHCA and 1 (3.3 %) for IHCA, while 22 (73.3 %) reported tracheal tubes for IHCA and only 9 (31 %) for OHCA. Open-ended responses emphasised the importance of guidance in low-resource settings.

CONCLUSION: Current ALS practices vary across countries, and between OHCA and IHCA settings with a need to consider low-resource settings. Understanding these practices has implications for guideline development and research planning.}, } @article {pmid40777853, year = {2025}, author = {Zhao, Q and Zhang, B and Chen, X and Fu, P and Yang, Y and Wang, Q}, title = {Global, regional, and national burden of motor neuron disease in adults aged 65 years and older from 1990 to 2021 and forecast to 2040.}, journal = {Frontiers in neurology}, volume = {16}, number = {}, pages = {1641887}, pmid = {40777853}, issn = {1664-2295}, abstract = {AIM: Given the significant social burden of motor neuron disease (MND) among elderly patients (aged ≥ 65 years) and the lack of detailed research on its epidemiological characteristics, this study aims to elucidate the temporal trends and distributional characteristics of MND in the elderly from 1990 to 2021, as well as to forecast its future burden.

METHODS: The age-standardized rates (ASR) and absolute numbers of MND-related incident, prevalent, death, and disability-adjusted life years (DALYs) among older patients (aged ≥ 65 years) globally were derived from the Global Burden of Disease (GBD) study from 1990 to 2021. The data were derived by gender, age group and geographic region. An estimated annual percentage change (EAPC) was estimated to represent temporal trends, and a Bayesian Age-Period-Cohort model was used to forecast the future burden of elderly MND.

RESULTS: In 2021, the global ASRs of incidence, prevalence, mortality, and DALYs for elderly MND were 3.63 (95% uncertainty intervals [UI], 2.95-4.36), 11.45 (95% UI, 8.69-14.88), 3.28(95% UI, 2.90-3.61), and 59.92 (95% UI, 53.94-65.53), respectively. Elderly patients those were from high socio-demographic index (SDI) region, as well as males, exhibited the highest burden. From 1990 to 2021, the global ASRs of elderly MND increased, with EAPCs of 0.43 (95% confidence interval [CI], 0.38-0.49), 0.58 (95% CI, 0.48-0.68), 0.90 (95%CI, 0.75-1.06), and 0.84 (95% CI, 0.71-0.96), respectively. Positive correlations were found between sociodemographic index and the burden of elderly MND. Health inequalities were evident across 204 countries and regions, with the inequality slope index raised from 23.46 (95% CI: 18.52-28.40) in 1990 to 80.70 (95% CI: 65.07-96.32) in 2021. Compared to the figures observed in 2021, our forecasts indicate a continued rise in the burden of elderly MND up to 2040, with the projected ASIR expected to reach 3.15 (95% UI, 2.28-4.01) and the ASMR anticipated to be 3.32 (95% UI, 2.11-4.55).

CONCLUSION: The burden of MND among elderly patients is substantial, particularly in high SDI region and among males. From 1990 to 2021, the global burden of elderly MND has exhibited an increasing trend. The burden of elderly MND varies significantly across the world, necessitating more targeted screening strategies and preventive measures to address the issue of elderly MND.}, } @article {pmid40777082, year = {2025}, author = {Otomo, A and Nishijima, K and Murakami, Y and Ishikawa, M and Yudahira, H and Shimakura, K and Okano, H and Aoki, M and Kimura, H and Hadano, S}, title = {Investigation of early axonal phenotypes in an iPSC-derived ALS cellular model using a microfluidic device.}, journal = {Frontiers in cellular neuroscience}, volume = {19}, number = {}, pages = {1590732}, pmid = {40777082}, issn = {1662-5102}, abstract = {INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease caused by the loss of upper and lower motor neurons. Mutations in the FUS/TLS gene have been reported as the second most common mutation in Japanese patients with familial ALS. In recent years, lower motor neurons (LMNs) differentiated from induced pluripotent stem cells (iPSCs) derived from ALS patients have been widely used to analyze the mechanisms of neuronal cell death and degeneration.

METHODS: In this study, we developed a microfluidic device designed to observe axonal growth, morphology, and trafficking at high resolution in neurons derived from induced pluripotent stem cells (iPSCs) and tested whether our microfluidic device effectively evaluates neurodegenerative phenotypes. We used iPSCs carrying homozygous FUS/TLS mutations (FUS_H517D) to induce LMNs by expressing NEUROG2, ISL1, and LHX3 under the control of the tetracycline regulation system.

RESULTS AND DISCUSSIONS: After seven days of in vitro differentiation (DIV7), we confirmed that over 95% of iPSCs differentiated into HB9-positive LMNs. Notably, the cell viability of FUS_H517D LMNs was comparable to that of LMNs differentiated from iPSCs without the FUS/TLS mutation at DIV7. However, by DIV14 and DIV21, the viability of FUS_H517D LMNs was notably lower than that of control LMNs, indicating degeneration of FUS_H517D LMNs after differentiation. Using our microfluidic device, we assessed axonal phenotypes in FUS_H517D LMNs. Under oxidative stress conditions, we observed that the axonal length of FUS_H517D LMNs was significantly shorter than that of control cells as early as DIV7, with this axonal growth restriction becoming more pronounced by DIV11. This suggests that axonal growth restriction is an early detectable phenotype in degenerating neurons. Additionally, we examined mitochondrial trafficking within axons in our device, which is often disrupted in degenerative neurons. Our results showed a significant increase in the number of motile mitochondria in FUS_H517D LMNs, with retrograde transport accounting for a large portion of trafficking. Our microfluidic device-based culture and evaluation system using FUS_H517D LMNs offers a valuable ALS cellular model focused on early axonal phenotypes. This approach contributes to the study of molecular mechanisms underlying axonal degeneration in ALS.}, } @article {pmid40776984, year = {2025}, author = {Wen, D and Li, Q and Li, Y and Yan, W and Wang, Y and Liu, Y}, title = {OPTN deficiency through CRISPR/Cas9 downregulates autophagy and mitophagy in a SOD1-G93A-expressing transgenic cell line.}, journal = {IBRO neuroscience reports}, volume = {19}, number = {}, pages = {307-316}, pmid = {40776984}, issn = {2667-2421}, abstract = {Amyotrophic lateral sclerosis (ALS) is characterized by the loss of upper and lower motor neurons (MNs) and is the most common adult paralysis neurodegenerative disease. Dysregulated autophagy, which has been reported in the pathogenesis of familial ALS, has been found in superoxide dismutase 1 (SOD1) transgenic mice and cell lines. Optineurin (OPTN) is a signal regulator that coordinates many crucial cellular processes, including autophagy, mitophagy and aggrephagy. Recent studies have shown that OPTN gene mutations are correlated with ALS, glaucoma and Paget's disease of the bone. Indeed, defects in autophagosome-lysosome fusion have been reported in patients with ALS-associated OPTN mutations. However, the exact function of OPTN in the pathology of ALS remains unknown. To determine the function of OPTN, we generated OPTN-knockdown cell lines from SOD1-G93A-expressing NSC34 cells with the clustered regularly interspaced short palindromic repeats/associated system 9 (CRISPR/Cas9) approach. In our research, we observed that the loss of OPTN resulted in the impairment of autophagy and mitophagy pathways. Moreover, the mitochondrial transmembrane potential was depolarized by LV-sgRNA-OPTN. On the basis of observations of live cells, the production of reactive oxygen species (ROS) was increased, the autophagic flux decreased, and the autophagic flux merged with that of mitochondria according to confocal live-cell imaging. A decreased LC3-II and an increased p62 levels indicated that autophagy pathway activation was decreased. The protein levels of VDAC1 and TBK1 decreased after OPTN knockdown, suggesting that mitophagy was blocked. Our results suggest that OPTN plays a pivotal role in regulating autophagy and mitophagy.}, } @article {pmid40776416, year = {2025}, author = {Thiry, L and Pulimood, NS and Tang, YM and Stifani, S}, title = {Dysregulated Expression of Inflammasome and Extracellular Matrix Genes in C9orf72-ALS/FTD Microglia.}, journal = {ASN neuro}, volume = {17}, number = {1}, pages = {2542998}, doi = {10.1080/17590914.2025.2542998}, pmid = {40776416}, issn = {1759-0914}, mesh = {*Microglia/metabolism ; *C9orf72 Protein/genetics/metabolism ; *Amyotrophic Lateral Sclerosis/genetics/pathology/metabolism ; Humans ; *Inflammasomes/genetics/metabolism ; *Frontotemporal Dementia/genetics/pathology/metabolism ; Induced Pluripotent Stem Cells ; *Extracellular Matrix/genetics/metabolism ; DNA Repeat Expansion/genetics ; Cells, Cultured ; }, abstract = {Hexanucleotide repeat expansion (HRE) in the non-coding region of the gene C9orf72 is the most prevalent mutation in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The C9orf72 HRE contributes to neuron degeneration in ALS/FTD through both cell-autonomous mechanisms and non-cell autonomous disease processes involving glial cells such as microglia. The molecular mechanisms underlying the contribution of C9orf72-HRE microglia to neuron death in ALS/FTD remain to be fully elucidated. In this study, we generated microglia from human C9orf72-HRE and isogenic iPSCs using three different microglia derivation methods. RNA sequencing analysis reveals a cell-autonomous dysregulation of extracellular matrix (ECM) genes and genes involved in pathways underlying inflammasome activation in C9orf72-HRE microglia. In agreement with elevated expression of inflammasome components, conditioned media from C9orf72-HRE microglia enhance the death of C9orf72-HRE motor neurons implicating microglia-secreted molecules in non-cell autonomous mechanisms of C9orf72 HRE pathology. These findings suggest that aberrant activation of inflammasome-mediated mechanisms in C9orf72-HRE microglia results in a pro-inflammatory phenotype that contributes to non-cell autonomous mechanisms of motor neuron degeneration in ALS/FTD.}, } @article {pmid40775651, year = {2025}, author = {Li, MJ and Li, Q and Zhao, MM and Kim, H and Feng, RQ and Guo, MN and Heng, JP and Yang, JK and Liu, C}, title = {Spectrum and epidemiology of rare diseases in a Chinese natural population of 14.31 million residents, 2012-2023.}, journal = {Orphanet journal of rare diseases}, volume = {20}, number = {1}, pages = {410}, pmid = {40775651}, issn = {1750-1172}, support = {82341076//National Natural Science Foundation of China/ ; }, mesh = {Humans ; *Rare Diseases/epidemiology ; Female ; Male ; China/epidemiology ; Child ; Adolescent ; Adult ; Middle Aged ; Child, Preschool ; Young Adult ; Aged ; Infant ; Incidence ; Registries ; Infant, Newborn ; East Asian People ; }, abstract = {BACKGROUND: Rare diseases, though individually uncommon, collectively affect a significant portion of the population. However, their epidemiology in China remains underexplored. A population-based rare disease registry comprising 14.31 million individuals was conducted between 2012 and 2023 by the Beijing Municipal Health Big Data and Policy Research Center. Rare disease cases were identified via ICD-10 codes mapped to China's national rare disease lists (2018 and 2023) and international databases. Age-standardized incidence rates (ASIR) were calculated per 100,000 person-years with 95% confidence intervals.

RESULTS: Our analysis identified 12,371 rare disease cases, with the overall ASIR increasing from 6.109 in 2012 to 7.394 in 2023. Rare neurologic diseases accounted for 52.12% of cases, followed by systemic and rheumatologic diseases (16.89%) and rare neoplastic diseases (9.99%). The most frequently diagnosed rare diseases included generalized myasthenia gravis, ANCA-associated vasculitis, and malignant melanoma. Significant sex-based differences were observed, with female patients more affected by systemic and rheumatologic conditions, while male patients showed a higher incidence of respiratory disorders. Pediatric patients predominantly presented with inborn errors of metabolism and rare immune diseases. Comparisons with global data revealed notable disparities, such as a higher prevalence of Wilson's disease and a lower incidence of amyotrophic lateral sclerosis (ALS) in China.

CONCLUSIONS: This study represents the first large-scale, population-based analysis of rare diseases in China, revealing distinct epidemiological patterns. These findings underscore the critical need for healthcare policies that address the unique challenges posed by rare diseases in China.}, } @article {pmid40775435, year = {2025}, author = {Xu, W and Guo, Z and Guan, Y and Lv, S and Gao, X and Luo, W and Cheng, T and Shao, Z and Tao, B and Wang, T and Qiu, Z}, title = {Machine learning-based proteomics profiling of ALS identifies downregulation of RPS29 that maintains protein homeostasis and STMN2 level.}, journal = {Communications biology}, volume = {8}, number = {1}, pages = {1177}, pmid = {40775435}, issn = {2399-3642}, support = {82473207//National Natural Science Foundation of China (National Science Foundation of China)/ ; 32271000//National Natural Science Foundation of China (National Science Foundation of China)/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/metabolism/genetics/pathology ; Humans ; *Proteomics/methods ; *Machine Learning ; Down-Regulation ; *Ribosomal Proteins/metabolism/genetics ; Motor Neurons/metabolism ; *Proteostasis ; Animals ; Biomarkers/metabolism ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a devastating motor neuron disease. The molecular understanding of ALS is hampered by the lack of experimental models recapitulating disease heterogeneity and analytical framework integrating multi-omics datasets. Here, we developed a pipeline integrating machine learning and consensus clustering to analyze a large-scale dataset of patient-derived motor neuron models from Answer ALS. Compared to the transcriptome, proteomic profiling closely correlates with ALS pathology, which is interrogated to identify 110 proteomics-based biomarkers (Proteomics Markers for ALS 110, PMA110). Functional enrichment highlights dysregulation of ALS pathways, including protein translation and neuronal function. By integrating ALS subtype-specific proteins with patient postmortem proteomics, we found that RPS29 was consistently downregulated in ALS models and patient motor neurons. RPS29 is required for neuronal viability by maintaining ribosome profiling and accurate translation, and suppressing pathological translation. RPS29 downregulation suppresses translation of STMN2, an essential protein for motor neurons, in iPSC-derived motor neurons. Taken together, this study provides a robust framework for ALS proteomics, identifies RPS29 as a quality controller of protein translation, and presents a translational mechanism for STMN2 maintenance in ALS.}, } @article {pmid40775105, year = {2025}, author = {Pasternack, N and Paulsen, O and Nath, A}, title = {Machine learning predicts distinct biotypes of amyotrophic lateral sclerosis.}, journal = {European journal of human genetics : EJHG}, volume = {}, number = {}, pages = {}, pmid = {40775105}, issn = {1476-5438}, support = {NS003130//U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; NS003130//U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that is universally fatal and has no cure. Heterogeneity of clinical presentation, disease onset, and proposed pathological mechanisms are key reasons why developing impactful therapies for ALS has been challenging. Here we analyzed data from two postmortem cohorts: one with bulk transcriptomes from 297 ALS patients and a separate cohort of single cell transcriptomes from 23 ALS patients. Using unsupervised machine learning, we found three groups of ALS patients characterized by synaptic dysfunction (34%), neuronal regeneration (47%), and neuronal degeneration (19%). Each of these ALS subtypes had unique patterns of transcriptional dysregulation that could represent novel therapeutic targets. We then developed a supervised machine learning model that was about 80% accurate at predicting ALS subtype based on patient demographic and clinical data. Together, we established three biologically distinct subtypes of ALS that can be predicted by clinical and demographic data.}, } @article {pmid40774708, year = {2025}, author = {Brown, KR and Quinton, ML and Tidmarsh, G and Cumming, J}, title = {Athletes' access to, attitudes towards and experiences of help-seeking for mental health: a scoping review.}, journal = {BMJ open}, volume = {15}, number = {8}, pages = {e097492}, pmid = {40774708}, issn = {2044-6055}, mesh = {Humans ; *Athletes/psychology ; *Patient Acceptance of Health Care/psychology ; *Mental Health ; *Mental Disorders/therapy/psychology ; *Help-Seeking Behavior ; *Mental Health Services ; *Health Services Accessibility ; }, abstract = {OBJECTIVES: Athletes have been found to experience a similar prevalence of mental health issues to non-athletes. However, they are subjected to a greater array of barriers to help-seeking for mental health, including sport-specific factors. This scoping review synthesised the literature on athletes' access to, attitudes towards and experiences of help-seeking for mental health from formal (mental health professionals such as psychiatrists) and semiformal sources (those who are not mental health professionals but are a service provider such as a coach).

DESIGN: The Joanna Briggs Institute framework and recommendations were used alongside the Preferred Reporting Items for Systematic Reviews and Meta-Analyses-Protocols checklist for scoping reviews. This scoping review was predominantly informed by Arksey and O'Malley's framework for scoping reviews, supplemented by Levac et al's additional recommendations. Rickwood and colleagues' help-seeking frameworks informed the research question, inclusion/exclusion criteria and analysis.

DATA SOURCES: The search terms and synonyms of "athlete" AND "mental health" AND "help-seeking" were searched in PsychINFO, Embase, MEDLINE, APA PsychArticles Full Text, Web of Science Core Collection, Scopus, Sport Discus, CINAHL and Proquest (Education Database, Health & Medical Collection, Nursing & Allied Health database, Psychology Database, Public Health Database, Education Collection, and Medicine & Education). These searches were conducted at three time points between April 2022 and 2024.

ELIGIBILITY CRITERIA: The inclusion and exclusion criteria were initially predetermined and specified in the protocol paper published in BMJ Open. Primary research articles, interventions and systematic reviews that referred to semiformal and formal sources of support were included.

DATA EXTRACTION AND SYNTHESIS: The lead reviewer (KRB) screened all titles and abstracts, and full texts, and extracted data from all included studies. A second reviewer was involved in screening and extracting 20%-30% of studies at each stage. Findings were synthesised descriptively (eg, study population, data collection method and location of studies) and by content (eg, access, attitudes and experiences, sources of support, use of theory and the validity of quantitative measures used).

RESULTS: After screening 4954 titles and abstracts and 275 full texts in Covidence, 104 papers were included in the review. This comprised of 87 primary research articles, 13 interventions and 4 systematic reviews. Most of the primary articles and interventions were published in the USA (50%). 49.4% of the primary articles used quantitative methods, 34.5% used qualitative methods and 16.1% used mixed methods. Attitudes towards mental health help-seeking were investigated in 78.8% of the included studies, experiences of help-seeking in 53.8% and access to sources of support in 31.7% of studies. Of the primary articles and interventions, formal sources were investigated in 55% of studies, semiformal sources in 2% and both in 26% of studies.

CONCLUSIONS: This scoping review of 104 papers showed the benefit of using help-seeking frameworks to shape and analyse a review. Analysing the results using these frameworks provided a novel contribution to the literature, showing where the athlete help-seeking literature base is currently focused and identified gaps for further research. For example, there is a need for further research on athletes in less developed nations, more qualitative and mixed methods studies, and further research on athletes' access to mental health support and their interactions with semiformal sources. The results have applied implications in public health and sport by highlighting the different factors that impact athlete help-seeking, and therefore areas where they require support.}, } @article {pmid40774338, year = {2025}, author = {Honold, S and Loizides, A and Skalla, E and Gruber, L and Plaikner, M and Gruber, H}, title = {Minimally invasive ultrasound-guided carpal tunnel release: long-term clinical outcomes.}, journal = {Ultraschall in der Medizin (Stuttgart, Germany : 1980)}, volume = {}, number = {}, pages = {}, doi = {10.1055/a-2678-8214}, pmid = {40774338}, issn = {1438-8782}, abstract = {PURPOSE: In cases of severe or refractory carpal tunnel syndrome (CTS), carpal tunnel release (CTR) can be performed using open surgery, endoscopic techniques, or minimally invasive approaches under high-resolution ultrasound (HRUS) guidance. This study aimed to evaluate the long-term clinical outcomes following HRUS-guided CTR.

MATERIALS AND METHODS: A retrospective analysis was conducted on 302 HRUS-CTR cases performed. Patients available for a phone interview and had a minimum follow-up period of one year were assessed using the Boston Carpal Tunnel Questionnaire (BCTQ). Symptom severity and functional limitations were compared before and after the procedure.

RESULTS: Of the 302 cases screened, 111 cases had to be excluded due to unavailability for the phone call, missing data or death. Accordingly, 191 cases were included. The average patient age was 60.4 ± 15.5 years (range 19 to 87 years). 126 cases (66%) were female and 65 cases (34.0%) were male. Overall, there was a significant reduction of 91.9% in CTS-related symptom severity and frequency for all items recorded in the questionnaire. Similarly, a significant reduction of 84.8% in difficulties with all self-reported daily activities was found. In addition, the procedures were performed by four physicians showing no significant differences in technical success and symptoms reduction.

CONCLUSION: HRUS-CTR is a safe and effective method for the treatment of CTS, showing a statistically but mostly clinically significant reduction of symptom severity and hand discomfort, which persisted 1 year after release and should therefore be considered as an alternative approach to open or endoscopic CTR. Zusammenfassung: Ziel: Bei schwerem oder therapierefraktärem Karpaltunnelsyndrom (CTS) wird die Spaltung des Ligamentum transversum carpi (CTR) offen chirurgisch, endoskopisch oder minimal-invasiv unter hochauflösender Ultraschall-kontrolle (HRUS) durchgeführt. Diese Studie hatte zum Ziel, die langfristigen klinischen Ergebnisse nach HRUS-geführter CTR (HRUS-CTR) zu eruieren. Material und Methode: Eine retrospektive Analyse wurde an 302 HRUS-CTR-Fällen durchgeführt. Patienten, die für ein telefonisches Interview verfügbar waren und eine Nachbeobachtungszeit von mindestens einem Jahr hatten, wurden mit dem Boston Carpal Tunnel Questionnaire (BCTQ) untersucht. Die Schwere der Symptome und funktionelle Einschränkungen wurden vor und nach dem Verfahren verglichen. Ergebnisse: Von den 302 geprüften Fällen mussten 111 Fälle aufgrund der Nichtverfügbarkeit des Telefonanrufs, fehlender Daten oder des Todes ausgeschlossen werden. Dementsprechend wurden 191 Fälle aufgenommen. Das durchschnittliche Alter der Patienten betrug 60,4 ± 15,5 Jahre (19 - 87 Jahre). 126 Fälle (66%) waren weiblich und 65 Fälle (34,0%) männlich. Insgesamt gab es eine signifikante Reduktion von 91.9% der CTS-bedingten Symptomschwere und -häufigkeit für alle im Fragebogen erfassten Fragen. In ähnlicher Weise wurde eine signifikante Reduktion von 84.8% der Schwierigkeiten bei allen selbstberichteten täglichen Aktivitäten festgestellt. Zusätzlich wurden die Verfahren von vier Ärzten durchgeführt ohne Nachweis signifikanter Unterschiede im technischen Erfolg und in der Symptomreduktion. Schlussfolgerungen: HRUS-CTR ist eine sichere und effektive Methode zur Behandlung von CTS mit einer statistisch, aber vor allem über einem Jahr anhaltenden klinisch signifikanten Reduktion der Symptomschwere und des Handunbehagens und sollte daher als alternativer Ansatz zur offen-chirurgischen oder endoskopischen CTR in Betracht gezogen werden.}, } @article {pmid40773352, year = {2025}, author = {Setsu, S and Morimoto, S and Nakamura, S and Ozawa, F and Okano, H}, title = {Protocol for the induction of human spinal motor neurons from human induced pluripotent stem cells for studying amyotrophic lateral sclerosis.}, journal = {STAR protocols}, volume = {6}, number = {3}, pages = {104016}, pmid = {40773352}, issn = {2666-1667}, abstract = {Here, we present a protocol for inducing spinal lower motor neurons (LMNs) from human induced pluripotent stem cells (iPSCs). We describe steps for preparation of a chemically induced transitional state (CTraS), transduction with Sendai virus, and LMN differentiation and maintenance. We then detail procedures for live imaging for single-cell-based survival analysis and neurite length of LMNs using BioStation and immunocytochemistry for induction efficiency check. This protocol is optimized for amyotrophic lateral sclerosis (ALS) research and large-scale screening. For complete details on the use and execution of this protocol, please refer to Setsu et al.[1].}, } @article {pmid40772974, year = {2025}, author = {Anjum, F and Bakhuraysah, MM and Hulbah, MJ and Alsharif, A and Mohammad, T and Hassan, MI}, title = {Aggregation-Prone Pathogenic SOD1 Variants in Amyotrophic Lateral Sclerosis: Insights from Computational Genomics and Evolutionary Conservation.}, journal = {Journal of molecular neuroscience : MN}, volume = {75}, number = {3}, pages = {99}, pmid = {40772974}, issn = {1559-1166}, support = {KSRG-2024-446//King Salman Center for Disability Research/ ; KSRG-2024-446//King Salman Center for Disability Research/ ; KSRG-2024-446//King Salman Center for Disability Research/ ; KSRG-2024-446//King Salman Center for Disability Research/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/genetics/metabolism ; *Superoxide Dismutase-1/genetics/chemistry/metabolism ; Humans ; *Mutation, Missense ; Evolution, Molecular ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by progressive motor neuron degeneration and a median survival of 3-5 years post-diagnosis. While the etiology of ALS remains elusive, mutations in SOD1, encoding the Cu/Zn superoxide dismutase enzyme, are strongly associated with familial ALS (fALS). These mutations promote a toxic gain-of-function, primarily through SOD1 misfolding and aggregation. We systematically assessed 244 SOD1 missense mutations using a multi-tiered computational framework encompassing structural, functional, and pathogenic predictors. Sequence-based predictors (SIFT, PolyPhen-2, FATHMM) and structure-guided tools (mCSM, PremPS, DynaMut2) identified 79 destabilizing mutations, 64 of which were classified as pathogenic by phenotype predictors (PhD-SNP, SNPs&GO, MutPred2). Twelve mutations resided in evolutionarily conserved regions, with eight (D84N, G73C, H72Y, P67A, P67R, P67S, R144G, S60I) exhibiting pronounced aggregation propensity via SODA analysis. Notably, H72Y disrupts a zinc-binding residue critical for structural integrity and catalysis. Protein-protein interaction networks linked SOD1 to ALS-associated pathways, highlighting its involvement in oxidative stress and protein homeostasis. Our integrative approach highlights the power of computational genomics in unraveling mutation-driven SOD1 dysfunction, offering mechanistic insights into ALS pathogenesis and guiding therapeutic strategies focused on aggregation-prone variants.}, } @article {pmid40772881, year = {2025}, author = {Zheng, Y and Li, M and Chen, X and Zheng, Z and Chen, Z and Tian, R and Zhao, YG}, title = {SOD1 is delivered to lysosomes via autophagy to maintain lysosomal function and integrity.}, journal = {The Journal of cell biology}, volume = {224}, number = {10}, pages = {}, doi = {10.1083/jcb.202501007}, pmid = {40772881}, issn = {1540-8140}, support = {32222021//National Natural Science Foundation of China/ ; 32170753//National Natural Science Foundation of China/ ; 2021YFA1300800//National Key Research and Development Program/ ; 2021 ZT09Y104//Guangdong Innovative and Entrepreneurial Research Team Program/ ; KQTD20210811090115021//Shenzhen Talent Program/ ; ZDSYS20220402111000001//Shenzhen Science and Technology Innovation Program/ ; GZNL2024A01008//R&D Program of Guangzhou Laboratory/ ; 2021QN02Y378//Guangdong Program/ ; //SUSTech Distinguished Young Scientist Team Program/ ; }, mesh = {*Lysosomes/metabolism/enzymology ; *Autophagy ; *Superoxide Dismutase-1/metabolism/genetics ; Humans ; Reactive Oxygen Species/metabolism ; Amyotrophic Lateral Sclerosis/genetics/pathology/enzymology ; Animals ; HEK293 Cells ; Autophagy-Related Protein 8 Family/metabolism/genetics ; Mice ; }, abstract = {The gene encoding superoxide dismutase 1 (SOD1) is often mutated in familial amyotrophic lateral sclerosis (ALS), affecting motor neurons. Compared with ALS-associated mutant SOD1, the function of WT SOD1 is less explored. We demonstrate that during starvation, WT and mutant SOD1 are transported into lysosomes. Genome-wide CRISPR interference (CRISPRi) screening identified autophagy-related proteins and the autophagic receptor TP53INP1 as key mediators. TP53INP1 binds ATG8 family proteins, preferentially LC3C, and directly interacts with SOD1. Within lysosomes, SOD1 retains its enzymatic activity. Starvation induces elevated levels of lysosomal reactive oxygen species (ROS), which are further increased by knocking down SOD1 or TP53INP1. Lysosomal degradation activities and membrane integrity are also compromised in the absence of SOD1 or TP53INP1. We reveal a novel function of SOD1 in maintaining lysosomal activity and integrity, and a previously unrecognized role of autophagy in delivering cytosolic enzymes into lysosomes for catalytic purposes, rather than for degradation.}, } @article {pmid40772655, year = {2025}, author = {He, J and Fan, D}, title = {Amyotrophic lateral sclerosis in Mainland China: clinical translational challenges and opportunities.}, journal = {Current opinion in neurology}, volume = {}, number = {}, pages = {}, pmid = {40772655}, issn = {1473-6551}, abstract = {PURPOSE OF REVIEW: Amyotrophic lateral sclerosis (ALS) imposes a growing medical and socioeconomic burden in China. This review synthesizes recent advances in understanding ALS epidemiology, biomarker discovery, therapeutic innovations, and policy frameworks in China. It highlights the urgency of addressing challenges, including fragmented healthcare resources, translational medicine gaps, and regional inequities, while emphasizing China's unique contributions to global ALS research.

RECENT FINDINGS: Chinese ALS cohorts exhibit distinct epidemiological profiles, including a younger mean age of onset and prolonged median survival. Policy initiatives, such as ALS inclusion in rare disease registries and insurance reforms, aim to reduce financial burdens of patients. Multimodal biomarker exploration has advanced integrated diagnostic models combining neurofilament light chain (NfL) and clinical data platforms. Neuroimaging and electrophysiological studies reveal glymphatic dysfunction, white matter degeneration, and neuromuscular junction abnormalities, with novel links to hepatic metabolism. Genomic analyses identify population-specific variants. Therapeutic innovations in China include not only biopharmaceuticals, but also integrative traditional Chinese medicine (TCM) approaches.

SUMMARY: China's ALS landscape is transitioning towards precision medicine through biomarker-guided diagnostics and multidisciplinary care models. Key priorities include establishing a national ALS registry, standardizing biomarker validation, and expanding clinical trials to bridge translational medicine gaps.}, } @article {pmid40772638, year = {2025}, author = {Menge, S and Decker, L and Freischmidt, A}, title = {Genetics of ALS - genes and modifier.}, journal = {Current opinion in neurology}, volume = {}, number = {}, pages = {}, pmid = {40772638}, issn = {1473-6551}, abstract = {PURPOSE OF REVIEW: Amyotrophic lateral sclerosis (ALS) is a complex genetic disorder, and the pace of discoveries is very rapid. This review aims at briefly summarizing our current knowledge, and at discussing the progress of the last two years.

RECENT FINDINGS: Common variation in numerous genes and variants in some nuclear-encoded mitochondrial genes were linked to an increased or modified risk of ALS, respectively. Mitochondrial function, i.e. specific mitochondrial haplotypes and loss-of-function variants in mitochondria-related genes, was identified as potent modifier of ALS survival, but not risk. Pioneering analyses of copy number variations in ALS-related genes revealed an increased load in ALS, but causality is unclear. A rare hyperactive variant of ER stress associated transcription factor CREB3 was linked to both substantially decreased ALS risk and slower disease progression. Furthermore, variants in IGFBP7 were linked to rare "ALS reversals", but existence of such phenotypes is controversial.

SUMMARY: Common variation increasing ALS risk contributes to our understanding of sporadic ALS, and novel structural variants have the potential to at least partly explain the missing heritability in ALS. Identification of mitochondrial function and ER stress signaling as potent disease modifiers provide valuable starting points for therapeutic approaches beyond targeting single causative genes.}, } @article {pmid40772263, year = {2025}, author = {Atwal, MS and Nimac, J and Čerček, U and Goesch, SR and Goesch, HR and Tziortzouda, P and Ercolani, T and Zatorska, A and Pasha, T and Carre, I and Mitchell, J and Troakes, C and Tummers, B and Župunski, V and Rogelj, B and Hortobágyi, T and Hirth, F}, title = {Accumulation of TDP-43 causes karyopherin-α4 pathology that characterises amyotrophic lateral sclerosis.}, journal = {Frontiers in neuroscience}, volume = {19}, number = {}, pages = {1558227}, pmid = {40772263}, issn = {1662-4548}, abstract = {Cytoplasmic mislocalisation and nuclear depletion of TDP-43 are pathological hallmarks of amyotrophic lateral sclerosis (ALS), including mutations in the C9ORF72 gene that characterise the most common genetic form of ALS (C9ALS). Studies in human cells and animal models have associated cytoplasmic mislocalisation of TDP-43 with abnormalities in nuclear transport receptors, referred to as karyopherins, that mediate the nucleocytoplasmic shuttling of TDP-43. Yet the relationship between karyopherin abnormalities and TDP-43 pathology are unclear. Here we report karyopherin-α4 (KPNA4) pathology in the spinal cord of TDP-43-positive sporadic ALS and C9ALS patients. Structural analyses revealed the selective interaction between KPNA subtypes, especially KPNA4, with the nuclear localisation signal (NLS) of TDP-43. Targeted cytoplasmic mislocalisation and nuclear depletion of TDP-43 caused KPNA4 pathology in human cells. Similar phenotypes were observed in Drosophila whereby cytoplasmic accumulation of the TDP-43 homolog, TBPH, caused the nuclear decrease and cytosolic mislocalisation of the KPNA4 homolog, Importin-α3 (Impα3). In contrast, induced accumulation of Impα3 was not sufficient to cause TBPH mislocalisation. Instead, targeted gain of Impα3 in the presence of accumulating cytosolic TBPH, restored Impα3 localisation and partially rescued nuclear TBPH. These results demonstrate that cytoplasmic accumulation of TDP-43 causes karyopherin pathology that characterises ALS spinal cord. Together with earlier reports, our findings establish KPNA4 abnormalities as a molecular signature of TDP-43 proteinopathies and identify it as a potential therapeutic target to sustain nuclear TDP-43 essential for cellular homeostasis affected in ALS and frontotemporal dementia.}, } @article {pmid40771731, year = {2025}, author = {Shi, DD and Tian, J and Ding, J}, title = {Adenosine deaminase in pleural effusion: Bridging diagnosis and the pathophysiology of inflammation.}, journal = {World journal of clinical cases}, volume = {13}, number = {22}, pages = {106925}, pmid = {40771731}, issn = {2307-8960}, abstract = {This editorial underscores the importance of Maranhão et al's study, which investigates pleural adenosine deaminase (P-ADA) as a biomarker for inflammatory pleural effusions. Despite advances in imaging, distinguishing between inflammatory and non-inflammatory causes of pleural effusion remains a diagnostic challenge. The authors conducted a rigorous retrospective cohort analysis of 157 patients (124 with inflammatory exudates and 33 with non-inflammatory transudates), establishing a robust cutoff value of P-ADA ≥ 9.00 U/L for diagnosing inflammatory diseases using receiver operating characteristic curve analysis and internal statistical calibration. This is the first study to define a standardized P-ADA threshold in a Brazilian cohort, addressing previous inconsistencies in cutoff values. Furthermore, the authors delved into the pathophysiological mechanisms underlying elevated P-ADA, linking it to purinergic signaling pathways and immune cell activation, particularly emphasizing the role of ADA2 isoforms in macrophages and lymphocytes. Their findings support P-ADA as a non-invasive, cost-effective biomarker for early diagnosis, treatment stratification, and minimizing the need for invasive procedures such as thoracentesis. This has particular relevance in resource-limited settings, where streamlined diagnostics can reduce healthcare costs and improve patient outcomes. Future studies must prioritize global validation, explore the integration of adenosine deaminase with additional biomarkers (e.g., interleukin 6, C-reactive protein), and support the development of point-of-care technologies.}, } @article {pmid40771035, year = {2025}, author = {Hattori, N and Mukai, Y and Nishikawa, N and Hasegawa, K and Tomiyama, M and Kimura, Y and Tsuboi, Y and Takahashi, R and Nakamura, R and Izumi, Y and Watanabe, H and Seki, M and Sekiguchi, K and Tateishi, S and Matsushita, Y and Nakamura, Y}, title = {Efficacy and Safety of IncobotulinumtoxinA for Treatment of Sialorrhea: A Multicenter, Phase 3 Study in Japan.}, journal = {Movement disorders clinical practice}, volume = {}, number = {}, pages = {}, doi = {10.1002/mdc3.70259}, pmid = {40771035}, issn = {2330-1619}, support = {//Teijin Pharma/ ; }, abstract = {BACKGROUND: Sialorrhea, caused by various neurological diseases, impairs patient health and quality of life. After the results of a randomized controlled trial, incobotulinumtoxinA was approved for the treatment of chronic sialorrhea in the United States and Europe; however, no pharmacotherapy has been approved in Japan.

OBJECTIVE: The aim was to evaluate the efficacy and safety of incobotulinumtoxinA treatment for chronic sialorrhea in a single-arm phase 3 study in Japan.

METHODS: Patients with chronic sialorrhea caused by neurological diseases (Parkinson's disease, atypical parkinsonism, and stroke, group A) and broader diseases (eg, muscular dystrophy and amyotrophic lateral sclerosis, group B) were enrolled. IncobotulinumtoxinA 100 U was injected into the salivary glands once every 16 weeks for 48 weeks. A primary endpoint was assessed in group A, whereas secondary endpoints and safety were assessed in both groups.

RESULTS: From November 2021 to August 2023, 92 patients (58 and 34 in groups A and B, respectively) received incobotulinumtoxinA at 28 institutions. The primary endpoint, the least square mean (standard error) of change in unstimulated salivary flow rate from baseline to 4 weeks, was -0.08 (0.009, 95% confidence interval [CI]: -0.10, -0.06) g/min, achieving the prespecified efficacy criteria (upper limit of the 95% CI <-0.04). The secondary endpoints were consistent across efficacy measures, indicating that reduced salivary secretion and improved drooling symptoms persisted for 48 weeks. The most common adverse events were dry mouth and dysphagia.

CONCLUSIONS: The first study in Japan confirmed the efficacy of incobotulinumtoxinA treatment for chronic sialorrhea with good patient tolerability and no new safety concerns.}, } @article {pmid40767769, year = {2025}, author = {Petre, AM and Thieschafer, JS and Palsuledesai, C and Cornille, K and Chang, A and Li, L and Distefano, MD}, title = {In Vivo Metabolic Labeling with an Isoprenoid Probe Reveals APOE Allele-Specific Differences in the Prenylome.}, journal = {ACS chemical biology}, volume = {20}, number = {8}, pages = {1951-1961}, doi = {10.1021/acschembio.5c00320}, pmid = {40767769}, issn = {1554-8937}, abstract = {Prenylation is a ubiquitous process in eukaryotes consisting of the irreversible post-translational modification of proteins through the attachment of a lipophilic isoprenoid moiety to a cysteine residue near their C-terminus. Due to the important functional roles of prenylated proteins, their participation and/or dysregulation has been linked to numerous diseases, including ALS, progeria, cancer, and Alzheimer's disease (AD). In humans, the APOE4 variant is the greatest known genetic risk factor for late-onset sporadic AD with carriers of two E4 alleles having up to 15 times the risk of developing AD. To begin to unravel the potential relationship between protein prenylation, AD, and APOE variants, it is necessary to study whether different APOE genotypes affect protein prenylation systemically. In the work described here, a methodology for metabolic labeling of prenylated proteins in living mice was first developed. It was then applied to humanized mouse strains that carry human APOE3 or APOE4 alleles. Prenylomic profiling revealed that a number of prenylated proteins were present at higher levels in animals harboring the APOE4 gene compared with those with the APOE3 allele, especially in the liver─a major APOE-producing organ. Importantly, some of these proteins have links to AD neuropathology.}, } @article {pmid40767591, year = {2025}, author = {Garrou, F and De Marchi, F and Corrado, L and Sacchetti, GM and D'alfonso, S and Morbelli, SD and Perani, D and Mazzini, L and Tondo, G}, title = {Challenging the boundaries: c9orf72 mutation presenting as Alzheimer's disease.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {}, number = {}, pages = {1-4}, doi = {10.1080/21678421.2025.2541761}, pmid = {40767591}, issn = {2167-9223}, abstract = {C9orf72 hexanucleotide repeat expansion is a major cause of Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD), while its link with Alzheimer's disease (AD) is still unclear. We describe the case of a 53-year-old man with progressive memory and language deficits, mood disturbances, and a positive family history for ALS-FTD. Cerebrospinal fluid showed amyloid positivity, confirmed by amyloid-PET, with normal tau levels; [[18]F]FDG-PET revealed an AD-like temporoparietal hypometabolism. Genetic testing detected a pathogenic C9orf72 expansion, also present in his mother. This case suggests phenotypic heterogeneity of C9orf72-related disorders and a possible interplay with amyloid pathology.}, } @article {pmid40767546, year = {2025}, author = {Dupuis, L and Robertson, J}, title = {Is amyotrophic lateral sclerosis less severe in mice than in humans?.}, journal = {Current opinion in neurology}, volume = {}, number = {}, pages = {}, pmid = {40767546}, issn = {1473-6551}, abstract = {PURPOSE OF REVIEW: We review here novel knock-in models of amyotrophic lateral sclerosis (ALS).

RECENT FINDINGS: Knock-in mouse models of various familial forms of ALS generally display a mild motor phenotype, with limited progression, that do not recapitulate the full-blown clinical picture of ALS.

SUMMARY: ALS is a devastating neurodegenerative disease in humans. Typically manifesting in the fifth or sixth decade of life, ALS leads to progressive motor dysfunction and death, usually within 2-5 years from symptom onset. A subset of ALS cases are dominantly inherited. Over the last 30 years, multiple mouse models of ALS have been generated, and recent advances in mouse genome editing techniques have enabled the generation of mouse strains carrying orthologous mutations in endogenous genes that mirror those causing familial forms of ALS. Intriguingly, many of these knock-in mouse models develop much milder phenotypes than patients with ALS carrying the same mutations. A full-blown ALS clinical phenotype seems to be only elicited upon overexpression of mutant genes beyond the endogenous levels. Here, we review these novel models and argue that these models could represent how ALS manifests in the mouse species. We also evaluate how these models could be used for characterizing mechanisms and preclinical drug evaluation.}, } @article {pmid40766632, year = {2025}, author = {Lacour, A and Vassallu, F and Rayes, D and Igaz, LM}, title = {Cytoplasmic TDP-43 leads to early functional impairments without neurodegeneration in a Serotonergic Neuron-Specific C. elegans Model.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {40766632}, issn = {2692-8205}, support = {P40 OD010440/OD/NIH HHS/United States ; }, abstract = {TDP-43 proteinopathies, such as amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), are marked by the pathological cytoplasmic accumulation of TAR DNA-binding protein 43 (TDP-43), leading to progressive neuronal dysfunction and degeneration. To investigate the early functional consequences of TDP-43 mislocalization, we generated Caenorhabditis elegans models expressing either wild-type human TDP-43 or a variant with a mutated nuclear localization signal (ΔNLS), specifically in serotonergic neurons. These neurons were chosen because i) serotonin deficits are a feature of ALS/FTD and ii) in C. elegans, they regulate well-characterized behaviors, providing a straightforward readout of neuronal function. We found that expression of either TDP-43 variant impaired serotonin-dependent behaviors-including pharyngeal pumping, egg-laying, and locomotion slowing upon food encounter-with the cytoplasmic ΔNLS form causing more severe deficits. Serotonergic neurons remained i) morphologically intact, indicating that neuronal dysfunction precedes overt neurodegeneration; and ii) partially responsive to the selective serotonin reuptake inhibitor fluoxetine, suggesting that neurotransmitter release is still partially functional. Altogether, our findings demonstrate that cytoplasmic TDP-43 disrupts neuronal signaling and behavior early in disease progression. This C. elegans model provides a genetically tractable system to dissect early mechanisms of TDP-43-mediated dysfunction and to identify therapeutic strategies targeting predegenerative stages of ALS/FTD.}, } @article {pmid40766389, year = {2025}, author = {Ferreon, JC and Choi, KJ and Quan, MD and Tsoi, PS and Ferreon, CC and Coskun, U and Liao, SJ and Ferreon, ACM}, title = {Modulation of biomolecular aggregate morphology and condensate infectivity.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2025.07.30.667758}, pmid = {40766389}, issn = {2692-8205}, abstract = {Neurodegenerative diseases are characterized by pathological aggregates exhibiting distinct morphologies, such as neurofibrillary tangles and dense circular Lewy body-like structures in Alzheimer's disease, and round hyaline gel-like inclusions and skein-like filaments in amyotrophic lateral sclerosis. However, the mechanisms driving the formation of these diverse morphological structures remain poorly understood. Employing advanced microscopy, including fluorescence lifetime imaging, we investigated condensate aging and aggregation mechanisms of the prion-like domain of hnRNPA1 (A1PrD), a ribonucleoprotein implicated in both disorders. Using a simplified system across various salt and RNA conditions, we demonstrate that homotypic and heterotypic interactions between A1PrD and RNA significantly influence aggregate morphology and amyloid fibril formation, yielding diverse structures including thin fibrils, solid gels, and filamentous starburst aggregates. By tracking aggregate morphogenesis, we observed shifts in fluorescence lifetimes that reflect differences in condensate microenvironments, highlighting distinct homotypic and heterotypic interaction dynamics. Our findings indicate that amyloid fibril formation can initiate within fluid condensates or at the interfaces of solid gels. Moreover, early amyloid-rich fluid starbursts demonstrated the capability to fuse with or recruit younger amyloid-poor droplets, exemplifying prion-like infectivity and accelerating fibril formation. Collectively, our study provides evidence that the interplay between solution composition and the kinetic balance of liquid-liquid phase separation, gelation, and fibrillation contributes to the diverse pathological aggregate morphologies observed in neurodegenerative diseases.}, } @article {pmid40766128, year = {2025}, author = {Homann, J and Smith, AG and Morgan, S and Frick, EA and Liu, F and Viallon, V and Maurya, R and Korologou-Linden, R and Dobricic, V and Ohlei, O and Deecke, L and Hajizadah, F and Zhao, Y and Artaud, F and Smith-Byrne, K and Kolijn, PM and Huerta, JM and Winter, N and Guevara, M and Jimenez-Zabala, A and Sánchez, MJ and Trobajo-Sanmartín, C and Cabrera-Castro, N and Vinagre, A and Petrova, D and Sieri, S and Key, TJ and Wareham, N and Kaaks, R and Travis, RC and Hahn, T and Baker, S and Kelly, SM and Vermeulen, R and Peters, S and Masala, G and Sacerdote, C and Finkel, N and , and Elbaz, A and Hess, M and Katzke, V and Bertram, L and Gudnason, V and Robinson, O and Chen, H and Middleton, L and Winchester, LM and Tzoulaki, I and Gudmundsdottir, V and Walker, KA and Ferrari, P and Riboli, E and Gunter, MJ and Lill, CM}, title = {Large-scale plasma proteomics uncovers preclinical molecular signatures of Parkinson's disease and overlap with other neurodegenerative disorders.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, doi = {10.1101/2025.07.30.25332433}, pmid = {40766128}, abstract = {Parkinson's disease (PD) remains incurable, with a long preclinical phase currently undetectable by existing methods. In the largest proteomic study in neurodegenerative diseases to date, we analyzed blood samples from ∼74,000 individuals across discovery and validation cohorts. In the EPIC4PD discovery case-cohort, large-scale profiling of 7,285 proteins (SomaScan-7K) in 4,538 initially unaffected participants (574 incident cases) identified 17 proteins that predict PD up to 28 years before diagnosis. Additional proteins revealed sex-specific effects and time-dependent effect trajectories, capturing disease progression before symptom onset. Replication in three prospective cohorts (n=64,856; 1,034 incident cases) confirmed at least 12 key pre-diagnostic biomarkers with strong evidence, including TPPP2, HPGDS, ALPL, MFAP5, OGFR, ACAD8, TCL1A, GPC4, GSTA3, LCN2, KRAS, and GJA1. Preclinical biomarkers showed 86% concordant effect directions in independent prevalent PD cases (n=2,592; p=1.6×10 [-19]). Furthermore, in the longitudinal Tracking PD cohort (n=794), HPGDS and MFAP5 also predicted cognitive decline. Notably, several of the identified PD biomarkers overlapped with those for incident Alzheimer's disease and amyotrophic lateral sclerosis, indicating shared molecular signatures. A machine learning-derived protein score improved PD risk prediction in external validation. This extensive proteomics effort identified novel, actionable biomarkers opening new avenues for early PD risk stratification and precision medicine.}, } @article {pmid40764817, year = {2025}, author = {Hu, Y and Chourpiliadis, C and Ingre, C and Ahlqvist, VH and Sun, J and Song, H and Pawitan, Y and Piehl, F and Fang, F}, title = {Hospital-treated infections and the risk and prognosis of amyotrophic lateral sclerosis: A population-based study.}, journal = {Journal of internal medicine}, volume = {}, number = {}, pages = {}, doi = {10.1111/joim.70008}, pmid = {40764817}, issn = {1365-2796}, support = {MegaALS 802091//European Research Council Starting Grant/ ; R01TS000348/ACL/ACL HHS/United States ; 2023-02428//Swedish Research Council/ ; 1R01NS131433-01//National Institute for Aging and the National Institute of Neurological Disorders and Stroke/ ; }, abstract = {BACKGROUND: Infection has been suspected as a risk factor for amyotrophic lateral sclerosis (ALS). However, previous research has focused on specific pathogens and rarely examined the influence of infection on disease progression.

OBJECTIVES: To assess whether hospital-treated infections correlate with the risk and prognosis of ALS.

METHODS: Using data from the Swedish Motor Neuron Disease Quality Registry, we conducted three nested case-control studies, including 1159 individuals diagnosed with ALS during 2015-2023 and 5795 age- and sex-matched population controls, 1558 full-sibling controls, and 680 spouse controls, respectively. We used conditional logistic regression to estimate the association of hospital-treated infections with subsequent risk of ALS and Cox model to assess the association of pre- or post-diagnostic infections with mortality after an ALS diagnosis.

RESULTS: Hospital-treated infections before diagnosis were associated with an increased risk of ALS in the population comparison (odds ratio [OR] 1.31; 95% confidence interval [CI] 1.15-1.49). A similar association was noted after excluding infections within 3-, 5-, or 10-years preceding ALS diagnosis and was confirmed in sibling and spouse comparisons, although results were not always statistically significant. Patients with a hospital-treated infection before diagnosis were more likely to present with bulbar symptoms, poorer functional status, and higher prevalence of anxiety and depressive symptoms at diagnosis than others. Pre-diagnostic infections were not associated with mortality, whereas post-diagnostic infections were associated with increased mortality (hazard ratio [HR] 1.89; 95%CI 1.59-2.24) among ALS patients.

CONCLUSION: Hospital-treated infections are associated with an increased risk of ALS and may modify its clinical presentation at diagnosis. Post-diagnostic infections are associated with poor survival in ALS.}, } @article {pmid40764463, year = {2025}, author = {Landry, C and Costanzo, JP and Mitne-Neto, M and Zatz, M and Schaffer, AE and Hatzoglou, M and Muotri, AR and Miranda, HC}, title = {Convergent activation of the integrated stress response and ER-mitochondria uncoupling in VAPB-associated ALS.}, journal = {EMBO molecular medicine}, volume = {}, number = {}, pages = {}, doi = {10.1038/s44321-025-00279-3}, pmid = {40764463}, issn = {1757-4684}, support = {K01NS116119//NIH NINDS/ ; R01NS123524/GF/NIH HHS/United States ; DK060596/GF/NIH HHS/United States ; }, abstract = {Vesicle-associated membrane protein-associated protein-B (VAPB) is an endoplasmic reticulum (ER) membrane-bound protein. The P56S mutation in VAPB causes a dominant, familial form of amyotrophic lateral sclerosis (ALS). However, the mechanism by which this mutation leads to motor neuron (MN) degeneration remains unclear. Utilizing inducible pluripotent stem cell (iPSC)-derived MNs expressing either wild-type (WT) or P56S VAPB, we demonstrate that the mutant protein reduces neuronal firing and disrupts ER-mitochondria-associated membranes (ER MAMs), with a time-dependent decline in mitochondrial membrane potential (MMP), hallmarks of MN pathology. These findings were validated in patient-derived iPSC-MNs. Additionally, VAPB P56S MNs show increased susceptibility to ER stress, elevated expression of the Integrated Stress Response (ISR) regulator ATF4 under stress, and reduced global protein synthesis. Notably, pharmacological ISR inhibition using ISRIB rescued ALS-associated phenotypes in both VAPB P56S and patient-derived iPSC-MNs. We present the first evidence that the VAPB P56S mutation activates ISR signaling via mitochondrial dysfunction in human MNs. These findings support ISR modulation as a strategy for ALS intervention and highlight the need for patient stratification in clinical trials.}, } @article {pmid40764342, year = {2025}, author = {Lépine, S and Maussion, G and Schneider, A and Nauleau-Javaudin, A and Castellanos-Montiel, MJ and Ambriz, GJ and Spiegelman, D and Abdian, N and Franco-Flores, AK and Haghi, G and Gursu, L and Fiorini, MR and Dilliott, AA and Farhan, SMK and Chaineau, M and Durcan, TM}, title = {Transcriptome-based screening in TARDBP/TDP-43 knock-in motor neurons identifies the NEDD8-activating enzyme inhibitor MLN4924.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {28555}, pmid = {40764342}, issn = {2045-2322}, mesh = {*Pyrimidines/pharmacology ; Humans ; *Motor Neurons/metabolism/drug effects ; Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology ; *DNA-Binding Proteins/genetics/metabolism ; *Cyclopentanes/pharmacology ; *Transcriptome ; *NEDD8 Protein/metabolism/antagonists & inhibitors ; Gene Knock-In Techniques ; Gene Expression Profiling ; Mutation ; Induced Pluripotent Stem Cells/metabolism ; }, abstract = {A growing body of knowledge implicates perturbed RNA homeostasis in amyotrophic lateral sclerosis (ALS), a neurodegenerative disease that currently has no cure and few available treatments. Dysregulation of the multifunctional RNA-binding protein TDP-43 is increasingly regarded as a convergent feature of this disease, evidenced at the neuropathological level by the detection of TDP-43 pathology in most patient tissues, and at the genetic level by the identification of disease-associated mutations in its coding gene TARDBP. To characterize the transcriptional landscape induced by TARDBP mutations, we performed whole-transcriptome profiling of motor neurons (MNs) differentiated from two knock-in iPSC lines expressing the ALS-linked TDP-43 variants p.A382T or p.G348C. Our results show that the TARDBP mutations significantly altered the expression profiles of mRNAs and microRNAs of the 14q32 cluster in MNs. Using mutation-induced gene signatures and the Connectivity Map database, we identified compounds predicted to restore gene expression toward wild-type levels. Among top-scoring compounds selected for further investigation, the NEDD8-activating enzyme inhibitor MLN4924 effectively improved cell viability and neuronal activity, highlighting a possible role for protein post-translational modification via NEDDylation in the pathobiology of TDP-43 in ALS.}, } @article {pmid40764041, year = {2025}, author = {Nguyen, M and Orengo, JP and Grouls, A}, title = {Letter: Advance Care Planning Documentation Changes Among Neurologists in an Amyotrophic Lateral Sclerosis Clinic with Addition of Specialist Palliative Care.}, journal = {Journal of palliative medicine}, volume = {}, number = {}, pages = {}, doi = {10.1177/10966218251365262}, pmid = {40764041}, issn = {1557-7740}, } @article {pmid40763713, year = {2025}, author = {Linna, N and Tervonen, LA and Aaltonen, M and Portaankorva, AM and Krüger, J}, title = {Epidemiology of Amyotrophic Lateral Sclerosis in Western and Northern Finland.}, journal = {Neuroepidemiology}, volume = {}, number = {}, pages = {1-18}, doi = {10.1159/000547562}, pmid = {40763713}, issn = {1423-0208}, abstract = {INTRODUCTION: The aims of this study were to define the incidence and prevalence of amyotrophic lateral sclerosis (ALS) in two north-western regions in Finland and to assess clinical ALS phenotypes in these areas.

METHODS: We conducted a retrospective epidemiologic study by using hospital discharge registers in the regions of Central Ostrobothnia (population 68 158 in 2019) and Northern Ostrobothnia (population 412 830). All patients diagnosed with ALS during 2010-2019 and living in either region were included in the incidence study. The prevalence day was December 31, 2019. All ALS diagnoses were retrospectively re-evaluated and the clinical phenotype data reviewed and reassessed.

RESULTS: In total, 214 ALS patients were identified. The age-adjusted 10-year incidence of ALS was 5.4/100 000 person-years in Central Ostrobothnia and 4.6/100 000 person-years in Northern Ostrobothnia. The age-adjusted prevalence rates were 13.1 and 14.6/100 000, respectively. The mean survival after the diagnosis was 16.8 months. Frontotemporal dementia (FTD) was identified in 15% of all patients. ALS-FTD was relatively more common among patients with bulbar or respiratory onset ALS (25%) than among those with limb-onset ALS (8%). Approximately 13% of the ALS patients had a positive family history for ALS. Genetic testing had been performed in 53 % of all cases and the most tested mutations were C9orf72 hexanucleotide repeat expansion (32%) and D90A-SOD1 (40%). C9orf72 repeat expansion was detected in 8% and a D90A-SOD1 mutation in 6% of all cases, that is 26% and 14% of all tested cases, respectively.

CONCLUSION: The incidence and prevalence rates of ALS in Finland are among the highest in the world. ALS-FTD seems to be more common among patients with bulbar or respiratory onset ALS than among those with spinal-onset disease. Cognitive evaluation of ALS patients and offering a possibility to genetic testing should be systematic in clinical practise.}, } @article {pmid40762423, year = {2025}, author = {Mietzner, G and Lümkemann, L and Schreiber, F and Brüggemann, J and Benramadan, A and Al-Dubai, M and Sciarra, A and Knoll, C and Kuehn, E and Speck, O and Schreiber, S and Mattern, H}, title = {Assessing Arterial Patterns in the Motor Cortex With 7 Tesla Magnetic Resonance Imaging and Vessel Distance Mapping.}, journal = {Human brain mapping}, volume = {46}, number = {11}, pages = {e70311}, pmid = {40762423}, issn = {1097-0193}, support = {362321501//Deutsche Forschungsgemeinschaft/ ; 425899996//Deutsche Forschungsgemeinschaft/ ; 446268581//Deutsche Forschungsgemeinschaft/ ; 501214112//Deutsche Forschungsgemeinschaft/ ; BB-DARS//Deutsche Alzheimer Gesellschaft/ ; MD-DARS//Deutsche Alzheimer Gesellschaft/ ; }, mesh = {Humans ; *Motor Cortex/blood supply/diagnostic imaging/anatomy & histology ; Male ; *Magnetic Resonance Imaging/methods ; Female ; Adult ; Young Adult ; *Cerebral Arteries/diagnostic imaging/anatomy & histology ; Image Processing, Computer-Assisted ; Middle Aged ; }, abstract = {Leveraging high-resolution 7 T magnetic resonance imaging (MRI) and vessel distance mapping (VDM), the arterial supply patterns and dominances of the motor cortex, which could previously only be studied postmortem, were assessed in vivo and fully noninvasively. Beyond vessel patterns and dominances, the potential relation between the vascularization and the motor cortex thickness was studied. Twenty-one healthy participants underwent 7 T MRI scans to map arterial supply and motor cortex at 0.45 mm isotropic resolution. The motor cortex vasculature was segmented manually with vessel-specific labels. VDM was utilized to estimate the vessel-specific supply regions and, subsequently, assess vessel patterns and dominances. Statistical tests were applied to test if the vasculature impacts mean motor cortical thickness estimates. Vessel patterns, that is the presence of supplying vessels, were classified as three-, four-, and five-vessel patterns with a prevalence of 26.3%, 50.0%, and 23.7%, respectively. Vessel dominance, that is the ratio of supply volumes, of the ACA branches showed dominance of the pericallosal artery, callosomarginal artery, and equal contribution, in 34.2%, 34.2%, and 31.6% of the cases, respectively. For the MCA groups, the prevalence of precentral group dominance, central group dominances, and equal contribution was 13.2%, 34.2%, and 52.6%, respectively. Although the central and precentral groups were found in all hemispheres, the postcentral group was found in 28.9% of hemispheres with highly variable supply contribution. Statistical tests returned no significance for the effect of vessel patterns and dominances on the mean motor cortex thickness. With 7 T MRI and VDM, the motor cortex vascularization can be assessed fully noninvasively and longitudinally while providing overall good concordance with previous post mortem studies. Our comprehensive analysis of arterial motor cortex vascularization showed considerable variability between hemispheres, rendering the usage of pattern-specific atlases and analysis more suitable than single normative representations. The successful translation from post mortem to in vivo enables the study of vascular reserve in disorders affecting the motor cortex, such as ALS, and can be translated to other brain regions and neurodegenerative diseases in the future.}, } @article {pmid40762148, year = {2025}, author = {Mascias Cadavid, J and Mena Bravo, A and Barkhaus, P and Barnes, B and Benatar, M and Breevoort, S and Brown, A and Carter, GT and Crayle, J and Foucher, J and Heiman-Patterson, T and Hobson, E and Jackson, C and Jhooty, S and Mallon, E and Mcdermott, C and Pattee, G and Pierce, K and Pioro, E and Ratner, D and Rivner, M and Tito, E and Wicks, P and Bedlack, R}, title = {ALSUntangled #80: ISRIB (Integrated stress response InhiBitor).}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {}, number = {}, pages = {1-4}, doi = {10.1080/21678421.2025.2542919}, pmid = {40762148}, issn = {2167-9223}, abstract = {ALSUntangled reviews alternative and off-label treatments for people living with amyotrophic lateral sclerosis (PALS). Here we assess ISRIB, a molecule that attenuates the integrated stress response (ISR). The ISR is an intracellular signaling network through which cells normally respond to stress, but in ALS it appears to be overactive, leading to the formation of "stress granules" which some but not all investigators believe can triggerapoptotic cell death. ISRIB can attenuate the formation of these stress granules while still allowing parts of protein synthesis to continue. Pre-clinical data demonstrate that ISRIB is beneficial in cell models of ALS. A small number of patients taking ISRIB in Spain report symptomatic improvements with little or no side effects, though we have not been able to independently verify these benefits. There are no clinical trials evaluating ISRIB in any condition and questions about its solubility and bioavailability have arisen. Currently, we do not have enough evidence to endorse the use of ISRIB for treating ALS. We support further research in disease models and clinical trials to study pharmacokinetics, safety and efficacy.}, } @article {pmid40760897, year = {2025}, author = {Kicherova, OA and Doyan, YI and Kicherova, KP and Reichert, LI and Root, VA}, title = {[Sporadic form of Guam disease (ALS-parkinsonism-dementia complex)].}, journal = {Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova}, volume = {125}, number = {7}, pages = {135-141}, doi = {10.17116/jnevro2025125071135}, pmid = {40760897}, issn = {1997-7298}, mesh = {Humans ; Male ; Diagnosis, Differential ; *Frontotemporal Dementia/diagnosis ; Middle Aged ; Aged ; *Parkinsonian Disorders/diagnosis ; Female ; *Dementia/diagnosis ; }, abstract = {Guam disease (ALS-parkinsonism-dementia complex) is a rare endemic condition of progressive generalized degeneration of CNS neurons. Despite the apparent association of the disease with the Pacific region, sporadic cases of Guam disease have been described in other countries of the world, where the term "ALS with frontotemporal dementia" is used to refer to it. The authors cite their own clinical case of the disease, as well as discuss aspects of the clinical presentation, etiology, pathogenesis, diagnosis, and differential diagnosis of similar conditions.}, } @article {pmid40760788, year = {2025}, author = {Ke, S and Yan, J and Li, B and Feng, X}, title = {Causal Association Between Immune Cell Traits and Risk of Multiple Malignant and Nonmalignant CNS Diseases: A Mendelian Randomization and Single-Cell Transcriptomic Analysis.}, journal = {Brain and behavior}, volume = {15}, number = {8}, pages = {e70632}, pmid = {40760788}, issn = {2162-3279}, mesh = {Humans ; Mendelian Randomization Analysis ; Single-Cell Analysis ; Quantitative Trait Loci/genetics ; Glioblastoma/genetics/immunology ; *Central Nervous System Diseases/genetics/immunology ; Transcriptome ; Gene Expression Profiling ; Brain Neoplasms/genetics/immunology ; }, abstract = {BACKGROUND: The influence of immune cell traits (ICTs) on the onset of multiple brain diseases has been previously investigated; however, it is limited by the sample size or colocalization evidence. Besides, the impact remains inconclusive.

METHODS: We performed a Mendelian randomization (MR) study to elucidate the causal correlation between significant ICTs and diverse brain disorders and explored the biomarkers linked to glioblastoma (GBM), a form of solid tumor, by integrating expression quantitative trait locus (eQTL) and single-cell RNA sequencing (scRNA-seq) analyses. The nonnegative matrix factorization (NMF) method was utilized to reclassify malignant cells into distinct cell states. Related functional analyses at the scRNA-seq level were also performed.

RESULTS: We examined 731 ICTs across 13 brain disorders; impacts from these ICTs varied a lot across different brain diseases. Such ICTs mainly involved T/natural killer (NK) cell activation, B cell differentiation, and myeloid cell suppression or activation. Pleiotropy or heterogeneity in current results has been checked and excluded via sensitivity analyses. Specifically, colocalization analyses demonstrated protective roles of distinct ICTs in T/B/NK cell panels for amyotrophic lateral sclerosis (ALS) and GBM, while myeloid and human leukocyte antigen (HLA)-associated traits were associated with increased risk of Alzheimer's disease (AD), and then two memory cell traits were linked to the increased risk of major depressive disease (MDD). By NMF, we identified six distinct cell states within GBM cells. Furthermore, we established an eight-marker glioblastoma risk signature (GBRS) using scRNA-seq and eQTL data, with higher GBRS scores observed in the NFkB cluster and EGFR cluster, indicating their highlighted aggression among malignant cells. Epigallocatechin gallate could be an effective treatment candidate targeting the EGFR cluster via markers of SQLE and VCP.

CONCLUSION: Our findings identified causal effects of distinct ICTs on both malignant and nonmalignant brain diseases and underscored the pivotal role of neuroinflammation in their etiology. With combined evidence from eQTL and scRNA-seq, GBM could be better characterized and managed.}, } @article {pmid40760594, year = {2025}, author = {Zhang, Q and Zhou, X and Yang, G and Zhang, L}, title = {Atopic dermatitis in amyotrophic lateral sclerosis successfully treated by dupilumab: A case report.}, journal = {Medicine}, volume = {104}, number = {31}, pages = {e43737}, pmid = {40760594}, issn = {1536-5964}, mesh = {Humans ; Male ; Aged ; *Antibodies, Monoclonal, Humanized/therapeutic use/administration & dosage ; *Amyotrophic Lateral Sclerosis/complications ; *Dermatitis, Atopic/drug therapy/complications ; Pruritus/drug therapy/etiology ; }, abstract = {RATIONALE: Atopic dermatitis (AD) is a common skin disorder characterized by symmetric erythematous papules in flexural areas, with pruritus of varying intensity persisting throughout its course. Amyotrophic lateral sclerosis (ALS) is a neurological disease with progressive loss of muscle function, and its treatment remains a challenge worldwide. When patients suffer from both conditions, the skin issues are often overlooked by both physicians and family members. However, the pruritus becomes unbearable for the patients, particularly as they experience a progressive loss of the ability to scratch autonomously.

PATIENT CONCERNS: An elderly 75-year-old male patient with comorbid ALS and AD, suffering from prolonged pruritus, had lost faith in all topical and oral medications.

DIAGNOSIS: AD and ALS.

INTERVENTIONS: The patient received subcutaneous dupilumab with an initial 600 mg dose followed by 300 mg every 2 weeks, and was monitored for 12 weeks during follow-up.

OUTCOMES: The patient exhibited gradual reduction in pruritus severity and skin lesions throughout the treatment course. No adverse reactions other than mild conjunctivitis were reported.

LESSONS: This case demonstrates the successful application of dupilumab in an AD patient with comorbid ALS. It not only provides a clinically instructive case reference for dupilumab therapy in AD, but also underscores that pruritus in ALS patients warrants greater clinical attention.}, } @article {pmid40760014, year = {2025}, author = {Farahani, A and Hansen, JY and Bazinet, V and Shafiei, G and Collins, DL and Dadar, M and Kalra, S and Dagher, A and Misic, B}, title = {Network spreading and local biological vulnerability in amyotrophic lateral sclerosis.}, journal = {Communications biology}, volume = {8}, number = {1}, pages = {1153}, pmid = {40760014}, issn = {2399-3642}, support = {RGPIN-2017-04265//Canadian Network for Research and Innovation in Machining Technology, Natural Sciences and Engineering Research Council of Canada (NSERC Canadian Network for Research and Innovation in Machining Technology)/ ; PJT-180439//Gouvernement du Canada | Canadian Institutes of Health Research (Instituts de Recherche en Santé du Canada)/ ; CRC-2022-00169//Canada Research Chairs (Chaires de recherche du Canada)/ ; MJFF-021133//Michael J. Fox Foundation for Parkinson's Research (Michael J. Fox Foundation)/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/pathology/diagnostic imaging/metabolism/physiopathology/genetics ; Humans ; Female ; Atrophy ; Male ; Middle Aged ; *Motor Cortex/pathology/diagnostic imaging ; Magnetic Resonance Imaging ; Neuroimaging ; Aged ; }, abstract = {Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disease that predominantly targets the motor system. Spread of pathology is thought to be driven by both local vulnerability and network architecture. Namely, molecular and cellular features may confer vulnerability to specific neuronal populations, while synaptic contacts may also increase exposure to pathology in connected neuronal populations. However, these principles are typically studied in isolation and it remains unknown how local vulnerability and network spreading interact to shape cortical atrophy. Here, we investigate how network structure and local biological features shape the spatial patterning of atrophy in ALS. We analyze the Canadian ALS Neuroimaging Consortium (CALSNIC) dataset and estimate cortical atrophy using deformation based morphometry (DBM). The course of atrophy closely aligns with structural connectivity. Atrophy is also more likely to occur in regions that share similar metabolic profiles. Disease epicenters are located in motor cortex. Epicenter probability maps show transcriptomic enrichment for biological processes involved in mitochondrial function as well as support cells, including endothelial cells and pericytes. Finally, individual differences in epicenter location correspond to individual differences in clinical and cognitive symptoms and differentiate patient subtypes.}, } @article {pmid40759286, year = {2025}, author = {Gunner, G and Basu, H and Lu, Y and Bergstresser, M and Sun, L and Neel, D and Choi, SY and Chiu, IM}, title = {Gasdermin D is activated but does not drive neurodegeneration in SOD1[G93A] model of ALS: Implications for targeting pyroptosis.}, journal = {Neurobiology of disease}, volume = {214}, number = {}, pages = {107048}, doi = {10.1016/j.nbd.2025.107048}, pmid = {40759286}, issn = {1095-953X}, abstract = {Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive motor neuron loss, microgliosis, and neuroinflammation. While pyroptosis, an inflammatory form of programmed cell death, has been implicated in ALS, the specific role of Gasdermin D (GSDMD) - the primary executioner of pyroptosis - remains unexplored. In this study, we examined the function of GSDMD in the well-established SOD1[G93A] mouse model of ALS. Our results showed robust GSDMD activation in the spinal cords of SOD1[G93A] animals with elevated expression in Iba1+ microglia. To explore its role in disease progression, we bred C57Bl/6 J.SOD1[G93A] mice onto a C57Bl/6NJ.GSDMD-deficient background. In comparing SOD1[G93A]; Gsdmd+/+ and SOD1[G93A]; Gsdmd-/- mice, we found that Gsdmd loss did not affect disease onset, weight loss, or grip strength decline in either male or female animals. Notably, GSDMD deficiency resulted in a modest but statistically significant increase in mortality in SOD1[G93A] mice. Moreover, GSDMD absence had minimal impact on astrogliosis, microgliosis and motor neuron loss. These findings show that while GSDMD is activated in the ALS mouse model, its loss does not mitigate key ALS behavioral phenotypes, gliosis or motor neuron loss. This study provides insights into the potential therapeutic relevance of targeting pyroptosis and inflammatory pathways in ALS.}, } @article {pmid40758885, year = {2025}, author = {Miller, SL and Green, KM and Crone, B and Switzenberg, JA and Tank, EMH and Krans, A and Jansen-West, K and Wieland, CM and Ji, EW and Petrucelli, L and Barmada, SJ and Boyle, AP and Todd, PK}, title = {Cryptic intronic transcriptional initiation generates efficient endogenous mRNA templates for C9orf72-associated RAN translation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {122}, number = {32}, pages = {e2507334122}, doi = {10.1073/pnas.2507334122}, pmid = {40758885}, issn = {1091-6490}, support = {F31127371//HHS | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; F31NS100302//HHS | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; R01NS097542 P01NS08497 and R35NS097273//HHS | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; R01NS113943 and 1R56NS128110//HHS | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; R21HG011493 and R01GM144484//HHS | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; R01NS099280//HHS | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; BLRD BX004842//U.S. Department of Veterans Affairs (VA)/ ; }, mesh = {*C9orf72 Protein/genetics/metabolism ; Animals ; *Introns/genetics ; Humans ; *RNA, Messenger/genetics/metabolism ; Mice ; *Protein Biosynthesis ; Amyotrophic Lateral Sclerosis/genetics/metabolism ; Frontotemporal Dementia/genetics/metabolism ; DNA Repeat Expansion ; *ran GTP-Binding Protein/genetics/metabolism ; Transcription, Genetic ; }, abstract = {Intronic GGGGCC hexanucleotide repeat expansions in C9orf72 are the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Despite its intronic location, this repeat avidly supports synthesis of pathogenic dipeptide repeat (DPR) proteins via repeat-associated non-AUG (RAN) translation. However, the template RNA species that undergoes RAN translation endogenously remains unclear. Using long-read based 5' RNA ligase-mediated rapid amplification of cDNA ends (5' Repeat-RLM-RACE), we identified C9orf72 transcripts initiating within intron 1 in a C9BAC mouse model, patient-derived iNeurons, and iNeuron-derived polysomes. These cryptic m[7]G-capped mRNAs are at least partially polyadenylated and are more abundant than transcripts derived from intron retention or circular intron lariats. In RAN translation reporter assays, intronic template transcripts-even those with short (32 nucleotide) leaders-exhibited robust expression compared to exon-intron and repeat-containing lariat reporters. To assess endogenous repeat-containing lariat RNA contributions to RAN translation, we enhanced endogenous lariat stability by knocking down the lariat debranching enzyme Dbr1. However, this modulation did not impact DPR production in patient-derived iNeurons. These findings identify cryptic, linear, m[7]G-capped intron-initiating C9orf72 mRNAs as an endogenous template for RAN translation and DPR production, with implications for disease pathogenesis and therapeutic development.}, } @article {pmid40758370, year = {2025}, author = {Lam, K and Cenzer, I and Ankuda, CK and Levy, CR and Smith, AK and Covinsky, KE and Kotwal, AA}, title = {Social Participation Among Older Adults Before and After Long-Term Care Facility Entry.}, journal = {JAMA internal medicine}, volume = {}, number = {}, pages = {}, pmid = {40758370}, issn = {2168-6114}, abstract = {IMPORTANCE: Social participation is essential throughout life and is associated with decreased mortality and increased quality of life. It is unknown whether long-term care facility (LTCF) entry disrupts or facilitates it.

OBJECTIVES: To determine longitudinal trends in social participation before and after entry into nursing homes (NHs) and assisted living facilities (ALs) and to explore factors associated with participation.

This nationally representative longitudinal cohort study using prospectively collected annual data from the US National Health and Aging Trends Study from 2011 to 2019 included community-dwelling Medicare beneficiaries entering LTCFs. Interviews conducted 4 years before and 2 years after NH or AL entry (index date) were included. Data analysis was performed from September 16, 2022, to May 25, 2025.

MAIN OUTCOMES AND MEASURES: Two categories of social participation comprising 5 activities were assessed: socialization (visiting with friends or family and going out for enjoyment) and community participation (attending religious services, participating in clubs or other organized activities, and volunteering). Participation over time was modeled using linear splines before, upon, and after LTCF entry. Modified Poisson regressions were used to explore associations with maintaining and starting activities, adjusted for age, sex, race and ethnicity, and proxy response were used.

RESULTS: The total sample included 606 LTCF entrants (weighted mean [SD] age 85 [7.4] years, 404 female [66% weighted]), of whom 104 individuals were Black (7%), 23 Hispanic (4%), 464 White (86%); and 15 of any other race and ethnicity (3%). Before entry, social participation decreased in all activities (-4.7 to -2.0% annually). Of the total, 275 (44%) entered a NH and 331 (56%) entered an AL facility. Upon entry, going out for enjoyment decreased (-14.1%), but club participation and religious attendance increased (15.6% and 12.6%, respectively). Before LTCF entry, social participation decreased in all activities (-4.7 to -2.0% annually). After entry, going out for enjoyment decreased (-14.1%), but club participation and religious attendance (12.6%) increased (15.6% and 12.6%, respectively). In exploratory analyses, women were more likely to maintain visits (adjust risk ratio [aRR], 1.3; 95% CI, 1.1-1.5) and start attending religious services (aRR, 1.6; 95% CI, 1.0-2.8). NH residents were less likely to go out for enjoyment (aRR, 0.6; 95% CI, 0.5-0.8 for maintaining; aRR, 0.6; 95% CI, 0.4-1.0 for starting) and keep attending religious services (aRR, 0.7; 95% CI, 0.6-0.9). Black, Hispanic, and residents of other race or ethnicity were much less likely to start going out for enjoyment (aRR, 0.3; 95% CI, 0.1-0.8).

CONCLUSIONS AND RELEVANCE: This cohort study found that LTCF entry generally promoted community participation and reduced socialization. Benefits may be less likely among men, NH entrants, and residents of racial and ethnic minority groups.}, } @article {pmid40758256, year = {2025}, author = {Sharma, A and Nb, K}, title = {Dose-dependent effects of Arimoclomol in ALS: insights from a network meta-analysis.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {}, number = {}, pages = {}, pmid = {40758256}, issn = {1590-3478}, } @article {pmid40757593, year = {2024}, author = {Orsini, M and Pinto, WBVR and Sgobbi, P and Oliveira, ASB}, title = {PRKAG2 Variant, Motor Neuron Disease, and Parkinsonism: Fortuitous Association or a Potentially Underestimated Pathophysiological Mechanism?.}, journal = {Muscles (Basel, Switzerland)}, volume = {3}, number = {3}, pages = {235-241}, pmid = {40757593}, issn = {2813-0413}, abstract = {A 72-year-old Brazilian woman presented with a 4-year history of rest tremors of the hands, followed by slowness of movement, and a diagnosis of idiopathic Parkinson's disease. She was started on dopamine agonists with significant improvement. After three years, she complained about slowly progressive dysphagia, dysphonia, quadriparesis, and cramps and fasciculations. A neurological examination disclosed distal-dominant quadriparesis, dysarthria, atrophy and fasciculation of the tongue, global brisk tendon reflexes, fasciculations, bilateral ankle clonus, and moderate spasticity of the lower limbs. She had also palpitations, dyspnea, and one episode of paroxysmal atrial fibrillation. Electrocardiography revealed a short PR interval, a widened QRS complex, and the delta wave, suggestive of Wolff-Parkinson-White syndrome. Brain and spine MR imaging, a cerebrospinal fluid analysis, and general serum lab exams were unremarkable. Needle electromyography disclosed chronic denervation involving cervical, thoracic, lumbosacral, and bulbar levels associated with acute denervation, including positive sharp waves, fasciculations, and fibrillation potentials. This patient fulfilled the diagnostic criteria for amyotrophic lateral sclerosis associated with parkinsonism. A broad next-generation sequencing-based panel disclosed the presence of the novel heterozygous variant c.1247C > T (p.Pro416Leu) in the PRKAG2 gene (NM_016203.4). Clinicians must be aware of the possibility of PRKAG2 variants in complex clinical scenarios associating cardiac arrhythmia, preexcitation syndromes, hypertrophic cardiomyopathy, motor neuron disease, and parkinsonism.}, } @article {pmid40757018, year = {2025}, author = {Kato, N and Suzuki, R and Kaneko, H and Horimoto, Y}, title = {Effects of telerehabilitation on physical function and activities of daily living in patients with amyotrophic lateral sclerosis: a scoping review.}, journal = {Journal of physical therapy science}, volume = {37}, number = {8}, pages = {427-434}, pmid = {40757018}, issn = {0915-5287}, abstract = {[Purpose] This study aimed to clarify the effects of telerehabilitation on physical function and activities of daily living in patients with amyotrophic lateral sclerosis through a literature review. [Participants and Methods] We conducted a scoping review based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Extension for Scoping Reviews reporting guidelines. The PubMed, Scopus, Web of Science, and ProQuest databases were searched. Study design, type of interventions, telerehabilitation methods, adherence, effectiveness, adverse events, and patient satisfaction were extracted from the selected literature. [Results] Four case-series and one case-control study were identified. The interventions included respiratory muscle training (two studies), aerobic exercise, stretching, and comprehensive physical therapy (one study each). Various modalities were used, including videoconferencing, on-demand instructional videos, and real-time monitoring of vital signs using wearable devices. No serious adverse events were reported in any study. The dropout rate was 0-21%, and the compliance rate was 90%, indicating high adherence. Improvements in respiratory function and ADL were observed following respiratory rehabilitation. Patient satisfaction with telerehabilitation was high. [Conclusion] Telerehabilitation may improve adherence, respiratory function, and activities of daily living in patients with amyotrophic lateral sclerosis. However, its effects on other aspects of physical function remain unclear. Further high-quality studies are needed to establish evidence-based practices.}, } @article {pmid40755012, year = {2025}, author = {Chen, S and Xu, C and Liu, C and Li, J and Ke, S and Lu, Y and Huang, Y and Chen, J and Lin, F and Huang, H and Zou, Z}, title = {Immune checkpoint changes correlate with the progression and prognosis of amyotrophic lateral sclerosis.}, journal = {Annals of medicine}, volume = {57}, number = {1}, pages = {2540023}, pmid = {40755012}, issn = {1365-2060}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/immunology/blood/diagnosis ; Male ; Female ; Middle Aged ; Prognosis ; Disease Progression ; CD4-Positive T-Lymphocytes/immunology/metabolism ; Aged ; Biomarkers/blood ; *Programmed Cell Death 1 Receptor/blood/immunology ; Neurofilament Proteins/blood ; Adult ; Case-Control Studies ; Flow Cytometry ; *Immune Checkpoint Proteins/blood ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) urgently requires robust biomarkers for early diagnosis and prognostic stratification. This study aims to investigate the diagnostic and prognostic potential of membrane-bound and soluble immune checkpoint molecules in ALS pathogenesis.

METHODS: In the present study at Fujian Medical Union Hospital, 72 participants (46 ALS and 26 healthy controls [HC]) underwent flow cytometry analysis of PD-1 expression in CD4[+] T cells and its subsets. A second cohort (n = 93, 44 ALS, 30 HC and 19 ALS mimics [Mimics]) was evaluated using Luminex technology for 14 serum immune checkpoint molecules. A single-molecule array was used to screen the neurofilament light chain (NFL) in serum.

RESULTS: Flow cytometry revealed elevated PD1 expression in CD4[+] T cells, particularly in Th9 and Th17 subsets (p < 0.05). ALS patients exhibiting a greater percentage of PD-1 in CD4[+] T cells showed accelerated functional decline. Serum analyses identified four elevated soluble checkpoints in ALS versus both HCs and Mimics (sPD-1/sBTLA/sCTLA-4/sCD27, p < 0.05), with sCD28/TIM-3 showing higher in ALS than in Mimics, and sGITR/sCD137/sIDO/sCD80/sLAG3/sPD-L2 elevating in ALS compared to HCs. Soluble TIM-3 correlated inversely with ALSFRS-R, while sPD-L1 demonstrated dual associations: negative with ALSFRS-R and positive with NFL (all p < 0.05).

CONCLUSIONS: Our research demonstrated a considerable increase in membrane-bound and soluble PD-1 in ALS patients, correlating with disease progression and worse prognosis. Furthermore, we explored 13 other immune checkpoint molecules. Collectively, these molecules may be implicated in peripheral immune mechanisms underlying ALS pathogenesis. While baseline PD-1 levels show some association with prognosis, their elevation potentially indicates an unfavorable course.}, } @article {pmid40754996, year = {2025}, author = {Stam, R}, title = {Low frequency magnetic field exposure and neurodegenerative disease: systematic review of animal studies.}, journal = {Electromagnetic biology and medicine}, volume = {}, number = {}, pages = {1-15}, doi = {10.1080/15368378.2025.2540435}, pmid = {40754996}, issn = {1536-8386}, abstract = {Epidemiological studies have found an association between occupational exposure to low frequency magnetic fields and the occurrence of motor neuron disease and Alzheimer's disease. No association has been found for Parkinson's disease and the evidence for multiple sclerosis is insufficient. Animal models studying the effects of low frequency magnetic fields on neurodegenerative disease induction or progression could provide more evidence on causation and the underlying mechanisms. A systematic search and review was conducted of peer-reviewed research articles involving animal experiments on the effects of low frequency magnetic field exposure on behavioural and neuroanatomical outcomes relevant for neurodegenerative diseases in humans. Firstly, experimental studies in naive animals do not support a causal relationship between exposure to low frequency magnetic fields and the induction of neuropathology relevant for Alzheimer's disease, but the number of studies relevant for motor neuron disease, multiple sclerosis and Parkinson's disease is too limited to draw conclusions. Secondly, experimental studies in existing animal models for neurodegenerative disease support a therapeutic (beneficial) effect of low frequency magnetic field treatment on behavioural and neuroanatomical abnormalities relevant for dementia (including Alzheimer's disease), multiple sclerosis and Parkinson's disease and no effect on disease progression in models relevant for motor neuron disease.}, } @article {pmid40754251, year = {2025}, author = {Sepulveda, M and MartinezTraub, F and Ojeda, P and Mella, J and Ojeda, J and Pinto, C and Diaz, R and Rozas, P and Sepulveda, C and Kerr, B and Morales, V and Saaranen, M and Ruddock, L and Medinas, DB and Henriquez, JP and Hetz, C}, title = {Expression of amyotrophic lateral sclerosis associated protein disulfide isomerase A3 D217N variant recapitulates early morphological alterations at the neuromuscular junction.}, journal = {Neurobiology of disease}, volume = {214}, number = {}, pages = {107045}, doi = {10.1016/j.nbd.2025.107045}, pmid = {40754251}, issn = {1095-953X}, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by neuromuscular connectivity decline followed by motoneuron loss. Altered proteostasis is suggested as a transversal pathogenic mechanism, notably involving dysfunction at the level of the endoplasmic reticulum (ER). Protein disulfide isomerases (PDIs) are key enzymes that catalyze protein folding and disulfide bond formation in the ER. Importantly, PDIs function is disrupted in ALS. We previously identified mutations in the gene encoding PDIA3 (also known as Grp58 or ERp57) as risk factors for ALS, which were associated with altered neuromuscular junction (NMJ) organization when expressed in zebrafish, a phenotype recapitulated in PDIA3-null mice. Here, we generated a transgenic mouse line overexpressing the ALS-linked PDIA3 variant D217N and performed a comprehensive characterization of ALS-like features. The transgenic line exhibited moderate overexpression of mutant PDIA3[D217N], which led to morphological alterations at the NMJ resembling those observed in ALS models and patients, along with abnormal distribution of oxidative and glycolytic muscle fibers. However, mutant PDIA3[D217N] expression did not result in motor impairment, coordination deficits, or motoneuron loss. At the molecular level, we observed reduced expression of SV2 in the spinal cord, an important synaptic protein involved in NMJ function. Our findings further support the involvement of PDIA3 dysfunction as a risk factor in the emergence of early features of ALS.}, } @article {pmid40753166, year = {2025}, author = {Rothstein, JD and Keeley, O and Warlick, C and Miller, TM and Ly, CV and Glass, JD and Coyne, AN}, title = {Sporadic ALS induced pluripotent stem cell derived neurons reveal hallmarks of TDP-43 loss of function.}, journal = {Nature communications}, volume = {16}, number = {1}, pages = {7092}, pmid = {40753166}, issn = {2041-1723}, support = {NS132836//U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; }, mesh = {Humans ; *Induced Pluripotent Stem Cells/metabolism/pathology ; *Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology ; *DNA-Binding Proteins/metabolism/genetics ; *Neurons/metabolism/pathology ; C9orf72 Protein/genetics/metabolism ; Nuclear Pore/metabolism/pathology ; Male ; Nuclear Pore Complex Proteins/metabolism/genetics ; Female ; Brain/metabolism/pathology ; Frontotemporal Dementia/genetics/metabolism/pathology ; Middle Aged ; }, abstract = {Nuclear loss and cytoplasmic buildup of the RNA-binding protein TDP-43 is a hallmark of ALS and related disorders. While studies using artificial TDP-43 depletion in neurons have revealed changes in gene expression and splicing, their relevance to actual patients remained unclear. Induced pluripotent stem cell (iPSC)-derived neurons (iPSNs) from 180 individuals, including controls, C9orf72 ALS/FTD, and sporadic ALS (sALS) patients were used to generate and analyze ~32,500 qRT-PCR data points across 20 genes which identified variable, time-dependent signatures of TDP-43 loss of function in individual lines. Notably, the same changes were also seen in postmortem brain tissue from the same patients, confirming that iPSNs accurately model disease. Inducing damage to the nuclear pore complex, specifically by reducing the nucleoporin POM121 in healthy iPSNs, was enough to replicate the molecular changes associated with ALS/FTD TDP-43 dysfunction. This directly links nuclear pore integrity to TDP-43-related pathology. Encouragingly, repairing nuclear pore injury in sALS iPSNs restored normal gene processing disrupted by TDP-43 loss. This study (1) provides a valuable population-scale resource for studying TDP-43 dysfunction in ALS, (2) confirms that patient-derived iPSNs closely reflect disease processes seen in the brain, and (3) demonstrates that targeting nuclear pore injury may offer a promising therapeutic strategy in ALS.}, } @article {pmid40753073, year = {2025}, author = {Lv, G and Sayles, NM and Huang, Y and Mancinelli, C and McAvoy, K and Shneider, NA and Manfredi, G and Kawamata, H and Eliezer, D}, title = {Amyloid fibril structures link CHCHD10 and CHCHD2 to neurodegeneration.}, journal = {Nature communications}, volume = {16}, number = {1}, pages = {7121}, pmid = {40753073}, issn = {2041-1723}, support = {R01NS139141//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; RF1AG066493//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; R35NS122209//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; U01NS134684//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; F31AG077836//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; F31HL154651//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; S10OD028556//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; S10OD016320//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; S10OD026974//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; S10RR027699//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; P30CA016087//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; SF349247//Simons Foundation/ ; 961871-02//Muscular Dystrophy Association (Muscular Dystrophy Association Inc.)/ ; }, mesh = {Humans ; *Amyloid/metabolism/ultrastructure/chemistry/genetics ; *Mitochondrial Proteins/genetics/metabolism/chemistry/ultrastructure ; *DNA-Binding Proteins/genetics/metabolism/chemistry ; Cryoelectron Microscopy ; *Transcription Factors/genetics/metabolism/chemistry/ultrastructure ; Mutation ; *Neurodegenerative Diseases/genetics/metabolism ; Amyotrophic Lateral Sclerosis/genetics/metabolism ; Frontotemporal Dementia/genetics/metabolism ; Models, Molecular ; Parkinson Disease/genetics/metabolism ; }, abstract = {Mitochondrial proteins CHCHD10 and CHCHD2 are mutated in rare cases of heritable FTD, ALS and PD and aggregate in tissues affected by these diseases. Here, we show that both proteins form amyloid fibrils and report cryo-EM structures of fibrils formed from their disordered N-terminal domains. The ordered cores of these fibrils are comprised of a region highly conserved between the two proteins, and a subset of the CHCHD10 and CHCHD2 fibril structures share structural similarities and appear compatible with sequence variations in this region. In contrast, disease-associated mutations p.S59L in CHCHD10 and p.T61I in CHCHD2, situated within the ordered cores of these fibrils, cannot be accommodated by the wildtype structures and promote different protofilament folds and fibril structures. These results link CHCHD10 and CHCHD2 amyloid fibrils to neurodegeneration and further suggest that fibril formation by the WT proteins could also be involved in disease etiology.}, } @article {pmid40752076, year = {2025}, author = {Mamangam, S and Brimson, JM}, title = {Rhodamine-B induces amyotrophic lateral sclerosis symptoms like -behaviours in zebrafish.}, journal = {Aquatic toxicology (Amsterdam, Netherlands)}, volume = {287}, number = {}, pages = {107515}, doi = {10.1016/j.aquatox.2025.107515}, pmid = {40752076}, issn = {1879-1514}, abstract = {Rhodamine B (RhB), often misused as a food adulterant, accumulates in the brain, causing oxidative stress and neurodegeneration. However, its detrimental effects on molecular mechanisms still require further investigation. The zebrafish is a model organism for studying neurodegeneration and neuropathology. We aimed to investigate the impacts of RhB on neuro-molecular and behaviours in Adult male zebrafish. Zebrafish were exposed to varying RhB concentrations of 0.25, 0.5, 1.0 μM and Rotenone (RoT) of 0.5 μM for 21 days. Behavioural assessments, including the mirror test, shoal preference test, T-maze and Y-maze tests, and novel tank test, were conducted to evaluate the impact of RhB on zebrafish behaviour. Furthermore, biochemical, neurochemical, and histopathological changes in the zebrafish brains were analysed. The neuronal behaviour patterns, such as reduced anxiety-like behaviour, time spent near or interacting with the mirror image, and cognitive dysfunction, were significantly affected by RhB in a time-dose-dependent manner when compared to those of control zebrafish. The glutathione reductase, catalase, lipid peroxidation, and reactive oxygen species levels were significantly increased, and acetylcholinesterase, glutathione peroxidase, superoxide dismutase, butyrylcholinesterase, serotonin, dopamine, and monoamine oxidase A and B were significantly reduced when exposed to RhB, when compared to those of control zebrafish. The C9orf72, btg2, fus, cfos, vgf, drd1b, npas4a, egr1, pax6a, vgf, ubb, atxn2, ier2a, tradbpa, tuba812 and grin1a mRNA levels were significantly upregulated. At the same time, sod1, bdnf, gabra1, and gabra2a were significantly down-regulated in the brain of RhB-exposed zebrafish compared to the control fish. These results suggested that RhB exposure can induce neurodegeneration in zebrafish mimicking Amyotrophic Lateral Sclerosis (ALS).}, } @article {pmid40751692, year = {2025}, author = {Trudel, P and Quesnel-Olivo, MH and Blais, M and Ramanathan, U and Dupré, N}, title = {ALS patients and PAD: description and comparison of patients from a neuromuscular clinic in Canada.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {}, number = {}, pages = {1-7}, doi = {10.1080/21678421.2025.2539894}, pmid = {40751692}, issn = {2167-9223}, abstract = {OBJECTIVES: In Canada, patients with ALS (PALS) who meet specific criteria can request Medical Assistance in Dying (MAiD), also known as Physician-Assisted Death (PAD). However, little is known about the characteristics of those patients. This study describes PALS who died of MAiD and compares them with patients who died from natural disease complications.

METHODS: A retrospective study of 209 consecutive PALS' electronic medical records was performed. Patients selected had follow-up at the CHU de Québec-Université Laval and died between January 2014 and April 2023. Sociodemographic and disease evolution data were collected. Fisher's exact test and Kolmogorov-Smirnov tests were used.

RESULTS: The analysis included 174 patients. MAiD PALS (N = 64) were mainly males (54.7%), of median age 67 years, in a relationship (68.7%), and parents of adult children (71.9%). Both cohorts had similar past medical histories of depressive disorders (15%, p > 0.999). MAiD PALS elected to use percutaneous endoscopic gastrostomy (PEG) feeding in 18.7% of cases compared to 28.2% of PALS who died of complications of ALS (p = 0.203). Palliative care teams were significantly more likely to be involved with PALS elected to request MAiD (86.6%, p = 0.023).

DISCUSSION: PALS who request MAiD share similar demographic and clinical characteristics with those who died from natural disease progression in our cohort. Trends toward differences were observed, namely, in the rate of disease progression, with PALS who requested MAiD more likely to be fast progressors than their counterparts, and in PEG feeding use with ALS MAiD patients less likely to request it. Palliative care involvement was more prevalent with MAiD PALS.}, } @article {pmid40751342, year = {2025}, author = {Corcia, P and Erazo, D and Amador, MDM and Beltran, S and Bernard, E and Blasco, H and Boutoleau-Bretonniere, C and Bruneteau, G and Camdessanche, JP and Camu, W and Cassereau, J and Choumert, A and Codron, P and Cintas, P and De La Cruz, E and Danel, V and Desnuelle, C and Eyraud, N and Esselin, F and Fauret, AL and Lefilliatre, M and Fleury, MC and Genestet, S and Grapperon, AM and Guy, N and Jacquin-Piques, A and Beauvais, K and Lautrette, G and Le Masson, G and Mathis, S and Piegay, AS and Pittion-Vouyovitch, S and Sauleau, P and Soriani, MH and Vershueren, A and Mouzat, K and Guissart, C and Couratier, P and Vourc'h, P}, title = {Prevalence of SOD1 and C9orf72 Variants Among French ALS Population: The GENIALS Study.}, journal = {European journal of neurology}, volume = {32}, number = {8}, pages = {e70302}, pmid = {40751342}, issn = {1468-1331}, support = {//Biogen/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/epidemiology ; C9orf72 Protein ; Superoxide Dismutase-1/genetics ; France/epidemiology ; Female ; Male ; Middle Aged ; Aged ; Adult ; *Proteins/genetics ; Prevalence ; *Superoxide Dismutase/genetics ; Age of Onset ; Genetic Variation ; }, abstract = {RATIONALE: Amyotrophic Lateral Sclerosis (ALS) is a fatal motoneuron disease in which genetics plays a central role for both familial and sporadic ALS cases. Systematic genetic analysis for all ALS patients is recommended at the time of diagnosis, leading to an early proposal of specific genetic therapy. Currently, C9orf72 is considered the most frequently mutated gene in ALS. Patients with a SOD1 pathogenic or probably pathogenic variants (ACMG classification) are eligible for SOD1 antisense oligonucleotide therapy.

OBJECTIVE: To determine the frequency of SOD1 variants and C9orf72 G4C2 repeats in a French ALS population and to describe genotype-phenotype relationships.

MATERIAL AND METHODS: One thousand incident ALS patients were enrolled from 22 ALS centers in France and followed up for 12 months. Epidemiological, familial history, neurological data, and genetic status were collected.

MAIN RESULTS: C9orf72 G4C2 repeats and SOD1 variants were observed in 7.6% and 1.6%, respectively. Fifty percent of SOD1 patients and 51% of C9orf72 patients had sporadic ALS. Fifteen different SOD1 variants were identified within the five exons and one intron. C9orf72 patients had a significantly younger age at onset and a trend toward a faster progression compared to non-expanded C9orf72 patients. Moreover, among the non-SOD1 non-C9orf72 population, patients with at least one C9orf72 copy with two G4C2 repeats had a shorter disease duration.

CONCLUSION: This study confirms SOD1 variants low frequency in the French population and highlights the more rapid disease progression observed in patients carrying C9orf72 expansions. These findings underscore the importance of systematic genetic screening at diagnosis.}, } @article {pmid40750781, year = {2025}, author = {Arnold, J and Pathak, P and Jin, Y and Pont-Esteban, D and McCann, CM and Lehmacher, C and Bonadonna, JP and Lewko, T and Burke, KM and Cavanagh, S and Blaney, L and Rishe, K and Cole, T and Paganoni, S and Lin, D and Walsh, CJ}, title = {Personalized ML-based wearable robot control improves impaired arm function.}, journal = {Nature communications}, volume = {16}, number = {1}, pages = {7091}, pmid = {40750781}, issn = {2041-1723}, mesh = {Humans ; *Robotics/instrumentation/methods ; *Wearable Electronic Devices ; *Arm/physiopathology/physiology ; Male ; Biomechanical Phenomena ; Female ; Stroke Rehabilitation/instrumentation/methods ; Middle Aged ; Movement/physiology ; Adult ; Shoulder/physiopathology ; Aged ; Amyotrophic Lateral Sclerosis/physiopathology/rehabilitation ; Stroke/physiopathology ; Range of Motion, Articular ; }, abstract = {Portable wearable robots offer promise for assisting people with upper limb disabilities. However, movement variability between individuals and trade-offs between supportiveness and transparency complicate robot control during real-world tasks. We address these challenges by first developing a personalized ML intention detection model to decode user's motion intention from IMU and compression sensors. Second, we leverage a physics-based hysteresis model to enhance control transparency and adapt it for practical use in real-world tasks. Third, we combine and integrate these two models into a real-time controller to modulate the assistance level based on the user's intention and kinematic state. Fourth, we evaluate the effectiveness of our control strategy in improving arm function in a multi-day evaluation. For 5 individuals post-stroke and 4 living with ALS wearing a soft shoulder robot, we demonstrate that the controller identifies shoulder movement with 94.2% accuracy from minimal change in the shoulder angles (elevation: 3.4°, depression: 1.7°) and reduces arm-lowering force by 31.9% compared to a baseline controller. Furthermore, the robot improves movement quality by increasing their shoulder elevation/depression (17.5°), elbow (10.6°) and wrist flexion/extension (7.6°) ROMs; reducing trunk compensation (up to 25.4%); and improving hand-path efficiency (up to 53.8%).}, } @article {pmid40750607, year = {2025}, author = {Nógrádi, B and Molnár, K and Kristóf, R and Horváth, O and Huang, YT and Ridgway, Z and Elicegui, A and Fuertes-Alvarez, S and Alonso-Martin, S and Szebeni, GJ and Gémes, N and Ramadan, A and Smith, HL and Krizbai, IA and Patai, R and Siklós, L and Klivényi, P and Chaytow, H and Gillingwater, TH}, title = {The CCL2-CCR2 axis drives neuromuscular denervation in amyotrophic lateral sclerosis.}, journal = {Nature communications}, volume = {16}, number = {1}, pages = {7053}, pmid = {40750607}, issn = {2041-1723}, support = {2021/MNDS/RP/8430GILL//MND Scotland (Motor Neuron Disease Scotland)/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/immunology/pathology/metabolism/genetics ; *Receptors, CCR2/metabolism/genetics/immunology ; Animals ; *Chemokine CCL2/metabolism/immunology/genetics ; Humans ; Male ; *Neuromuscular Junction/pathology/metabolism/immunology ; Mice ; Muscle, Skeletal/pathology/metabolism/innervation/immunology ; Disease Models, Animal ; Macrophages/immunology/metabolism ; DNA-Binding Proteins/genetics/metabolism ; Female ; Mice, Transgenic ; Leukocytes/immunology/metabolism ; }, abstract = {Systemic immune changes have been implicated in amyotrophic lateral sclerosis (ALS), but precise mechanisms and cellular targets remain unknown. Neuromuscular junction (NMJ) denervation is another major pathophysiological event in ALS, but it remains unclear whether immune system dysregulation contributes to this process. Here, we report leukocyte and macrophage infiltration in ALS patient-derived skeletal muscle biopsies. Immune cell infiltration was replicated across the hTDP-43, TDP-43[A315T] (male only) and TDP-43[M337V] mouse models, occurring from pre-symptomatic stages and targeted to NMJ-enriched muscle regions. Proteomic analysis implicated the CCL2-CCR2 axis as a driving factor. CCL2[+] cells were enriched around NMJs in hTDP-43 mice, and in ALS patient skeletal muscle. Local treatment with CCL2-neutralising antibodies or normal IgG antibodies in hTDP-43 mice reduced leukocyte infiltration and ameliorated NMJ denervation. These results demonstrate that the CCL2-CCR2 axis drives immune cell infiltration targeting NMJs in ALS, identifying a potential avenue for therapeutic intervention to prevent NMJ denervation.}, } @article {pmid40747856, year = {2025}, author = {Guilfoyle, J and Fan, Y and SÁnchez-SoliÑo, O and Boiser, J and Vinikoor-Imler, L}, title = {Symptoms prior to diagnosis among a diverse patient population with amyotrophic lateral sclerosis In the USA.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {}, number = {}, pages = {1-9}, doi = {10.1080/21678421.2025.2538599}, pmid = {40747856}, issn = {2167-9223}, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) symptom onset is gradual and may include muscle weakness, dysarthria, dysphagia, and respiratory difficulties among others. The objective of this study is to describe sex and racial/ethnic variation in limb and bulbar symptom diagnoses before ALS diagnosis in the USA.

METHODS: This retrospective cohort study was conducted using Optum's de-identified Market Clarity Data with a patient identification period between January 2015 and December 2019. Cases were identified using ICD-9/10 codes and were required to have ≥3 years of continuous enrollment or EHR activity prior to diagnosis. Descriptive statistics of symptom frequency and onset were stratified by sex and race.

RESULTS: This study identified 7121 individuals with ALS, 3303 female (46%) and 3818 male (54%). Most identified as Non-Hispanic White (67.5%), followed by African American (6.6%), Hispanic (3.6%), and Asian (0.9%), with 21.4% missing race/ethnicity. In the 3 years before ALS diagnosis, 42.9% of subjects were diagnosed with ≥1 bulbar symptom, 74.5% with ≥1 limb symptom, and 34.6% with both. Females more likely to be diagnosed than males: any bulbar 47.1% versus 39.3%, (p < 0.0001), any limb 76.0% versus 73.2%, (p = 0.007), both 38.1% versus 31.6%, (p < 0.0001). Variation by race/ethnicity was observed for limb symptoms (p < 0.0001) and both bulbar and limb symptoms (p = 0.008), but not bulbar symptoms alone (p = 0.07). Symptom onset to ALS was longer for females and varied by race/ethnicity.

CONCLUSION: Females were more likely to present with bulbar and limb symptoms prior to ALS diagnosis and African American patients were more likely to present with limb symptoms than other race/ethnicities.}, } @article {pmid40747386, year = {2025}, author = {Arnold, WD and Castoro, R and Saxena, S}, title = {Innovations In Physical Medicine and Rehabilitation: Advances in the Diagnosis, Treatment, and Care of Amyotrophic Lateral Sclerosis.}, journal = {Missouri medicine}, volume = {122}, number = {3}, pages = {199-205}, pmid = {40747386}, issn = {0026-6620}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/therapy/rehabilitation ; *Physical and Rehabilitation Medicine/trends/methods ; Quality of Life ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive motor neuron disease that causes loss of upper and lower motor neurons, leading to muscle weakness and ultimately death. This review highlights recent advancements in Neuromuscular Medicine and Physical Medicine and Rehabilitation (PM&R), emphasizing innovations in the diagnosis, treatment, and care delivery for ALS. The field of PM&R emphasizes a multidisciplinary, patient-centered approach, incorporating advanced diagnostic tools, therapeutic strategies, adaptive equipment, and telerehabilitation to optimize function. Neuromuscular PM&R physicians play a key role in managing symptoms and maximizing functional independence. Current disease-modifying therapies include riluzole and edaravone which provide only modest benefits, but emerging gene therapies like tofersen for SOD1-related ALS offer promise for targeted treatment for genetic forms of ALS. Future advancements in regenerative therapies, biotechnologies, and digital health integration hold the potential to improve care and enhance the quality of life and functional independence of individuals living with ALS.}, } @article {pmid40747225, year = {2025}, author = {Li, J and Wang, W}, title = {Challenges of Klebsiella pneumoniae infections post-liver transplantation: Insights and future directions.}, journal = {World journal of hepatology}, volume = {17}, number = {7}, pages = {107213}, pmid = {40747225}, issn = {1948-5182}, abstract = {Klebsiella pneumoniae infections (KPIs), particularly carbapenem-resistant Klebsiella pneumoniae (CRKP), pose significant challenges in liver transplantation (LT) recipients, with high morbidity and mortality. Guo et al's study highlights risk factors, such as elevated day-one alanine aminotransferase levels and prolonged catheterization, and identifies polymyxin B and ceftazidime/avibactam as effective treatments. However, limitations like the absence of pre-transplant colonization data and host-pathogen interaction insights highlight the need for enhanced strategies. Future directions should include routine CRKP colonization surveillance, immune and genomic profiling, and the development of novel therapeutics. By integrating these approaches, we can improve the prevention, diagnosis, and treatment of KPIs in LT patients.}, } @article {pmid40746751, year = {2025}, author = {Sabetta, E and Rallmann, K and Bergquist, J and Taba, P and Pfaff, AL and Poudel, BH and Ferrari, D and Locatelli, M and Kõks, S}, title = {Comprehensive identification of pathogenic tandem repeat expansions in sporadic amyotrophic lateral sclerosis: advantages of long-read vs. short-read sequencing.}, journal = {Experimental biology and medicine (Maywood, N.J.)}, volume = {250}, number = {}, pages = {10593}, pmid = {40746751}, issn = {1535-3699}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics ; Male ; Female ; Middle Aged ; *DNA Repeat Expansion/genetics ; Aged ; Adult ; *Sequence Analysis, DNA/methods ; High-Throughput Nucleotide Sequencing/methods ; Whole Genome Sequencing/methods ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder presenting progressive weakness of the bulbar and extremity muscles, leading to a wide-ranging clinical phenotype. More than 30 genes have been associated to genetically inherited ALS yet, approximately 85%-90% of ALS cases are sporadic. Short tandem repeats expansions, have recently been found in clinically diagnosed ALS patients and are currently investigated as potential genetic biomarkers. In this paper we compare the investigation of pathological tandem repeat expansions on a group of ALS patients by comparing the standard short-read sequencing (SRS) technique with a long-read-sequencing (LRS) method which has recently become more accessible. Blood samples from 47 sporadic ALS cases were subjected to SRS by Illumina Whole Genome Sequencing. The genome-wide tandem repeat expansions were genotyped using GangSTR, while wANNOVAR was used for variant annotation. Uncertain cases were further explored using LRS. SRS identified pathological expansions in HTT, ATXN2, and CACNA1A genes in one patient, which were not confirmed with LRS. The latter identified large tandem repeat expansions in the C9orf72 gene of one patient that were missed by SRS. Our findings suggest that LRS should be preferred to SRS for accurate identification of pathological tandem repeat expansions.}, } @article {pmid40746624, year = {2025}, author = {Kashyap, PV and Singh, D and Nair, A and Jaiswal, A and Pandey, V}, title = {Effect of Edaravone Therapy on Amyotrophic Lateral Sclerosis Functional Rating Score (ALS-FRS) in Patients of Amyotrophic Lateral Sclerosis (ALS) in Central India: A Retrospective Open Label Study.}, journal = {Annals of neurosciences}, volume = {}, number = {}, pages = {09727531251357377}, pmid = {40746624}, issn = {0972-7531}, abstract = {BACKGROUND: Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disorder affecting motor neurons and is characterised by a diverse range of clinical manifestations. With the understanding of its pathophysiology, many treatments have emerged in last two decades. This study aims to evaluate the impact of intravenous Edaravone on Amyotrophy Lateral Sclerosis Functional Rating Scale (ALS-FRS) scores and patient survival outcomes of Amyotrophic Lateral Sclerosis patients in Central India.

METHODS: This retrospective study was conducted over a span of 2.5 years and included patients diagnosed with definitive or probable ALS, as per the revised El Escorial criteria. The effects of intravenous (IV) Edaravone on ALS-FRS-R scores were compared between two groups: the intervention group (patients who received IV Edaravone) and the non-intervention group (patients who did not receive IV Edaravone). Data collected included demographic details and ALS-FRS-R scores that were recorded at baseline after each treatment cycle, for a total six cycles. These scores were compared with those of the control group at the corresponding time points. Survival outcomes were also evaluated between the two groups and side effect profile of the drug was also noted.

RESULTS: Data of ALS patients (definitive and probable) were screened, and 62 patients were enrolled, of which 12 were excluded, thus there were 25 ALS patients in the intervention group and 25 patients in the non-intervention group. The two groups were matched for demographic parameters and the ALS-FRS scores were noted at the baseline at each cycle till 6 cycles and compared. It was inferred that the scores were not significant statistically (p > .001) among the two groups, nor did the survival rates vary significantly.

CONCLUSION: Intravenous Edaravone therapy had no beneficial effect on the ALS-FRS score in the intervention group when compared to the non-intervention group, nor did the survival rates improve. Keywords: Amyotrophic lateral sclerosis, Edaravone Therapy, ALS FRS Score.}, } @article {pmid40746518, year = {2025}, author = {Liu, QZ and Zeng, L and Sun, NZ}, title = {Radiomics for preoperative pancreatic ductal adenocarcinoma risk stratification: Cross-population validation, multidimensional integration, challenges, and future directions.}, journal = {World journal of radiology}, volume = {17}, number = {7}, pages = {110048}, pmid = {40746518}, issn = {1949-8470}, abstract = {This editorial critically evaluated Liu et al's recent retrospective analysis of 283 Chinese patients with resectable pancreatic ductal adenocarcinoma (PDAC) that validated a preoperative computed tomography-based risk scoring system originally developed in South Korea. The scoring system incorporated five parameters: (1) Tumor size; (2) Portal venous phase density; (3) Necrosis; (4) Peripancreatic infiltration; and (5) Suspected metastatic lymph nodes. While demonstrating satisfactory recurrence prediction capability without requiring complex technologies, thereby supporting clinical utility in Chinese populations, the study exhibited notable limitations. Most analyzed patients lacked neoadjuvant chemotherapy exposure, resulting in underrepresentation of low-risk subgroups. Additionally, the short follow-up duration potentially compromised long-term prognostic assessment. Contemporary advances in radiomics coupled with machine learning have enhanced multimodal data integration for PDAC management. However, clinical implementation continues to confront challenges including variability in imaging parameters, incomplete understanding of molecular underpinnings, and confounding treatment effects. Future investigations should prioritize developing multidimensional predictive frameworks that synergize radiographic, molecular, and clinical data. Prospective multicenter validation and artificial intelligence-powered real-time risk stratification systems represent essential steps to overcome current barriers in precision medicine translation, ultimately advancing personalized therapeutic strategies for PDAC.}, } @article {pmid40745959, year = {2025}, author = {Dogra, S and Kouznetsova, VL and Tsigelny, IF}, title = {Repurposing FDA-approved drugs for treatment of amyotrophic lateral sclerosis using machine learning.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {}, number = {}, pages = {1-9}, doi = {10.1080/21678421.2025.2536027}, pmid = {40745959}, issn = {2167-9223}, abstract = {INTRODUCTION: Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease characterized by loss of motor neurons. Current medications are largely ineffective, associated with side effects, and hindered by a lack of agreement over treatment pathways. The time-intensive process and high costs further limit the development of therapeutics. Therefore, this research aimed to identify FDA-approved drugs that inhibit three proteins (Casein kinase 1, Protein tyrosine kinase 2, Ephrin type-A receptor 4) associated with ALS.

METHODS: A machine learning (ML) model was trained for each protein to identify an inputted compound as an active inhibitor of that protein. The FDA-approved drugs were then screened through these models, and 18 drugs were identified as likely inhibitors for all three proteins. The results were validated through protein-ligand docking of each drug to its respective protein(s).

RESULTS: Risperidone was the most active drug, with an average ML score of 1 and binding affinity of -8.9. The ML scores and binding affinities had a strong correlation, indicating reliability.

CONCLUSION: This research predicted multiple drugs that can simultaneously target many proteins involved in ALS, creating more effective treatment options at a lower cost. This procedure can be applied to efficiently discover drugs for other diseases in the future.}, } @article {pmid40744617, year = {2025}, author = {Kaspary, TE and Cutti, L and Turra, GM and Angonese, PS and Dos Santos, OD and Merotto, A}, title = {Conyza bonariensis resistance to glyphosate and ALS inhibitors involves target and non-target site resistance.}, journal = {Pesticide biochemistry and physiology}, volume = {213}, number = {}, pages = {106501}, doi = {10.1016/j.pestbp.2025.106501}, pmid = {40744617}, issn = {1095-9939}, mesh = {Glyphosate ; *Herbicide Resistance/genetics ; *Glycine/analogs & derivatives/pharmacology ; *Herbicides/pharmacology ; *Acetolactate Synthase/antagonists & inhibitors/genetics/metabolism ; *Conyza/drug effects/genetics ; Mutation ; Plant Proteins/genetics/antagonists & inhibitors/metabolism ; }, abstract = {Herbicide resistance in Conyza bonariensis (hairy fleabane) poses a significant challenge to agricultural systems worldwide. The genetic variability and prolific seed production of this species contribute significantly to its adaptative potential and fast spread in the agricultural fields. This study aimed to investigate the mechanisms underlying multiple herbicide resistance to glyphosate and ALS inhibitors in C. bonariensis biotypes from Southern Brazil. Resistance factors exceeded 100 times for chlorimuron-ethyl and 49 times for glyphosate. DNA Sequencing revealed the target-site mutations Pro106Thr in the EPSPS gene conferring glyphosate resistance, and Pro197Arg and Trp574Leu in the ALS gene contributing to chlorimuron-ethyl resistance. Additionally, the resistance factor decreased at least 80 % for resistant biotypes after application of chlorimuron-ethyl following treatment with the P450 inhibitor malathion, which might indicate enhanced metabolism mediated by cytochrome P450 enzymes. Copy number variation and overexpression of ALS and EPSPS genes were not related to resistance. Biotype II carries the Pro197Arg mutation and exhibited cross-resistance to imazethapyr, diclosulam, bispyribac‑sodium, and flucarbazone‑sodium. Biotypes carrying the Trp574Leu mutation were resistant to imazethapyr, diclosulam and flucarbazone‑sodium but demonstrated varying resistance patterns to bispyribac‑sodium, highlighting the complexity of resistance mechanisms. These findings underscore the importance of understanding both target and non-target-site resistance mechanisms to develop effective management strategies, including herbicide rotation and molecular diagnostics, to mitigate the spread of herbicide-resistant C. bonariensis in agricultural systems.}, } @article {pmid40744595, year = {2025}, author = {Li, J and Zhang, Y and Li, L and Wei, S and Huang, Z and Chen, L and Huang, H}, title = {Expression of Echinochloa oryzoides CYP71A1 and GSTU23 catalyzes the metabolism of thiobencarb, thereby conferring resistance.}, journal = {Pesticide biochemistry and physiology}, volume = {213}, number = {}, pages = {106555}, doi = {10.1016/j.pestbp.2025.106555}, pmid = {40744595}, issn = {1095-9939}, mesh = {*Echinochloa/drug effects/genetics/metabolism/enzymology ; *Herbicide Resistance/genetics ; *Herbicides/pharmacology/metabolism ; *Cytochrome P-450 Enzyme System/metabolism/genetics ; *Thiocarbamates/metabolism/pharmacology ; *Plant Proteins/genetics/metabolism ; *Glutathione Transferase/metabolism/genetics ; }, abstract = {Echinochloa oryzoides (Ard.) Fritsch. is a notorious and prevalent weed in paddy fields. Thiobencarb (TB), a thiocarbamate herbicide, is widely applied in paddy fields for the control of pre-emergence weeds. However, owing to the prolonged and large-scale usage of TB, certain Echinochloa oryzoides populations have evolved resistance to it. In this study, a population of Echinochloa oryzoides from a paddy field was suspected of being resistant to the TB herbicide. Notably, this population also displayed multiple resistance and cross-resistance to Acetolactate synthase (ALS), Acetyl-CoA carboxylase (ACCase), and hormone-based herbicides. The resistance to TB was partially reversed by 50.8 % and 44.7 % upon treatment with a glutathione S-transferase (GST) inhibitor (NBD-Cl) and a cytochrome P450 inhibitor (malathion), respectively. This confirmed that metabolic resistance was the predominant mechanism underlying the observed resistance. RNA-seq analysis uncovered the overexpression of CYP71A1 and GSTU23 in the resistant (R) population. This study is the first to screen and validate metabolic enzymes capable of effectively metabolizing TB in an Echinochloa oryzoides. Functional verification was conducted using a yeast in vitro expression system, which confirmed the metabolic capabilities of both CYP71A1 and GSTU23 genes towards TB. Collectively, these findings demonstrate that the overexpression of CYP71A1 and GSTU23 in the R population endows Echinochloa oryzoides with the evolutionary capacity to develop resistance to thiobencarb. This study has shed light on the resistance mechanisms of Echinochloa oryzoides to TB, thereby enhancing our understanding of its herbicide tolerance. Moreover, these results highlight the necessity for targeted strategies to control resistant populations, ultimately contributing to more effective and sustainable herbicide resistance management in agriculture.}, } @article {pmid40744561, year = {2025}, author = {Mora, G and Gil-Monreal, M and Osuna, MD and Vijayarajan, VBA and Montull, JM and Llenes, JM and Recasens, J and Cirujeda, A and Marí, AI and Torra, J}, title = {First case of triple resistance to EPSPS, ALS, and synthetic auxin herbicides in Bassia scoparia (L.) Voss in Europe.}, journal = {Pesticide biochemistry and physiology}, volume = {213}, number = {}, pages = {106529}, doi = {10.1016/j.pestbp.2025.106529}, pmid = {40744561}, issn = {1095-9939}, mesh = {*Herbicides/pharmacology ; *Acetolactate Synthase/genetics/antagonists & inhibitors/metabolism ; *Herbicide Resistance/genetics ; *3-Phosphoshikimate 1-Carboxyvinyltransferase/antagonists & inhibitors/genetics/metabolism ; *Bassia scoparia/drug effects/genetics/enzymology ; *Indoleacetic Acids/pharmacology ; Plant Proteins/genetics/metabolism ; }, abstract = {Bassia scoparia (L.) Voss has evolved resistance to five herbicide modes of action (MoAs) worldwide, including multiple resistance to up to four MoAs. Seeds were collected from a putatively resistant B. scoparia population (GUI-R) that survived successive herbicide applications of synthetic auxins, acetolactate synthase (ALS), and 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) inhibitors in a no-till winter cereal field in Catalonia, Spain, in 2022, to assess resistance levels and mechanisms. Dose-response assays confirmed that GUI-R was 2-, 340-, 42.7-, and 60-fold more resistant to glyphosate, thifensulfuron, MCPA, and 2,4-D, respectively, based on plant weight, and 3.2-, 123-, 57.9-, and 32-fold more resistant based on plant survival. GUI-R showed cross-resistance to imazamox (46 % survival), but not to dicamba or fluroxypyr (100 % mortality), at the label rate. Preliminary studies using malathion pre-treatment, a cytochrome P450 inhibitor, reversed 2,4-D resistance in GUI-R at the label rate, resulting in a 97 % reduction in biomass. Molecular studies revealed that GUI-R has 4.9 additional copies of the EPSPS:ALS gene, with no known mutations and less shikimate accumulation than the susceptible population. ALS gene sequencing identified the Pro197Ser, Pro197Leu, and Trp574Leu mutations, along with a combined Pro197Ser + Trp574Leu mutation. In conclusion, EPSPS gene amplification and ALS mutations confer target-site resistance to glyphosate, thifensulfuron and imazamox in GUI-R. Resistance to 2,4-D and MCPA is probably driven by P450-mediated non-target-site resistance and further research is necessary to confirm mechanisms. This biotype represents the first case of glyphosate resistance in Europe for the species, as well as the first triple resistance.}, } @article {pmid40744389, year = {2025}, author = {Nelson, VK and Begum, MY and Suryadevara, PR and Madhuri Kallam, SD and Panda, SP and Bodapati, A and Sanga, V and Bishoyi, AK and Ballal, S and Monsi, M and Walia, C and Prasad, GVS and Abomughaid, MM and Shukla, S and Chauhan, P and Jha, NK}, title = {Natural Bioactive Compounds as Modulators of Autophagy: A Herbal Approach to the Management of Neurodegenerative Diseases.}, journal = {European journal of pharmacology}, volume = {}, number = {}, pages = {178003}, doi = {10.1016/j.ejphar.2025.178003}, pmid = {40744389}, issn = {1879-0712}, abstract = {Neurodegenerative diseases (NDs) such as Alzheimer's disease (AD), Parkinson's disease (PD), Polyglutamine (polyQ), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS) disease are a significant health concern that affects millions of people every year worldwide. The main pathological hallmark of various NDs is the formation of misfolded protein aggregation and accumulation of inclusion bodies. These protein aggregates are mainly responsible for producing toxic effects and initiating neuronal cell death, ultimately promoting various NDs. On the other hand, the patients suffering from these kinds of diseases live in impaired conditions, imposing a substantial financial burden on the family. However, the current treatment strategies can only offer temporary relief from the disease symptoms and can't reverse the disease completely. Hence, there is an urgent need for specific and novel drug treatment that can significantly eradicate NDs. Ubiquitin proteasome system (UPS) and autophagy are the two essential intracellular defensive mechanisms that are involved in clearing the protein aggregates, pathogens, and damaged organelles from the cytoplasm and maintaining protein homeostasis. Nevertheless, UPS is inefficient in removing some kinds of organelles and aggregating-prone proteins, specifically in neuronal and glial cells. Under this kind of circumstance, the autophagy mechanism plays a vital role in eliminating the accumulated protein aggregates and other toxic elements from the cytoplasm of the neuronal cells that initiate oxidative stress. However, in NDs, the autophagy function is impaired, and the protein aggregates can't be eliminated effectively. Hence, forced up-regulation of autophagy function by applying various external agents could be a potential therapeutic strategy to control NDs like AD, PD, HD, and ALS. In this review, we focused on different kinds of plant-derived compounds that induce autophagy. We also discussed the role of these plant-derived autophagy modulators in various NDs. In this way, the current review will be a standalone reference to the researchers working in this area.}, } @article {pmid40741338, year = {2025}, author = {Marek, A and Brož, B and Kriegelstein, M and Nováková, G and Hojcsková, J and Blechová, M and Žáková, L and Jiráček, J and Maletínská, L}, title = {Late-stage labeling of diverse peptides and proteins with iodine-125.}, journal = {Journal of pharmaceutical analysis}, volume = {15}, number = {7}, pages = {101198}, pmid = {40741338}, issn = {2214-0883}, abstract = {The preparation of specifically iodine-125 ([125]I)-labeled peptides of high purity and specific activity represents a key tool for the detailed characterization of their binding properties in interaction with their binding partners. Early synthetic methods for the incorporation of iodine faced challenges such as harsh reaction conditions, the use of strong oxidants and low reproducibility. Herein, we review well-established radiolabeling strategies available to incorporate radionuclide into a protein of interest, and our long-term experience with a mild, simple and generally applicable technique of [125]I late-stage-labeling of biomolecules using the Pierce iodination reagent for the direct solid-phase oxidation of radioactive iodide. General recommendations, tips, and details of optimized chromatographic conditions to isolate pure, specifically [125]I-mono-labeled biomolecules are illustrated on a diverse series of (poly)peptides, ranging up to 7.6 kDa and 67 amino acids (aa). These series include peptides that contain at least one tyrosine or histidine residue, along with those featuring disulfide crosslinking or lipophilic derivatization. This mild and straightforward late-stage-labeling technique is easily applicable to longer and more sensitive proteins, as demonstrated in the cases of the insulin-like growth factor binding protein-3 (IGF-BP-3) (29 kDa and 264 aa) and the acid-labile subunit (ALS) (93 kDa and 578 aa).}, } @article {pmid40740926, year = {2025}, author = {Ding, Y and Xing, YX and Sun, NZ}, title = {Managements of bile leakage after liver transplantation: Commentary on recent findings.}, journal = {World journal of gastrointestinal surgery}, volume = {17}, number = {7}, pages = {108148}, pmid = {40740926}, issn = {1948-9366}, abstract = {Bile leakage remains a formidable challenge in post-liver transplantation management, posing significant risks to patient outcomes and graft survival. This editorial provides a critical appraisal of the recent clinical study by Gu et al, which compared the efficacy of stent placement vs endoscopic nasobiliary drainage (ENBD) for treating post-transplant bile leaks. By retrospectively analyzing data from their institutional cohort of liver transplant recipients with bile leaks, the authors evaluated the therapeutic success rates and clinical outcomes between the stent and ENBD groups, with a focused discussion on the relative advantages of each approach. Gu et al demonstrated that both stent placement and ENBD were effective in managing post-transplant bile leaks, with comparable therapeutic outcomes. However, the study also recognized its limitations, such as the lack of an assessment of the impact of bile leak severity on outcome and the absence of long-term follow-up data. The editorial further highlights the pressing need for advancing research on long-term complications post-liver transplantation and underscores the pivotal role of clinical stratification and physician expertise in guiding therapeutic decisions. In summary, Gu et al's study enhances our understanding of mitigating post-transplant complications like bile leaks and offers evidence-based insights to refine clinical protocols. This commentary aims to contextualize current research trends and future directions in the field, advocating for sustained innovation and evidence-driven practice.}, } @article {pmid40740556, year = {2025}, author = {Mirenayat, MS and Fakharian, A and Valizadeh, M and Abedi, M and Sadeghi, S and Zahiri, R and Haghi Ashtiani, B and Masaebi, F and Zamani, B}, title = {Evaluation of Inspiratory Muscle Training Effect Compared With Diaphragmatic Breathing in Respiratory Parameters in Amyotrophic Lateral Sclerosis Patients: A Randomized Controlled Trial.}, journal = {Medical journal of the Islamic Republic of Iran}, volume = {39}, number = {}, pages = {37}, pmid = {40740556}, issn = {1016-1430}, abstract = {BACKGROUND: Many patients with amyotrophic lateral sclerosis (ALS) experience respiratory failure. The use of respiratory muscle training exercises can improve the respiratory function of these patients. This study aimed to evaluate the effect of inspiratory muscle training (IMT) on respiratory muscle function in ALS patients.

METHODS: In the current randomized controlled clinical trial study, 22 patients were randomly divided into intervention (n = 11) and control groups (n = 11). In the control group, patients used only chest-opening training and diaphragm exercises. Patients in the intervention group used IMT in addition to controlled exercises (chest opening training and diaphragm exercises). Respiratory function by spirometry and monitoring of maximum inspiratory and expiratory pressure, functional capacity with a 6-minute walk test, and arterial blood gases were also assessed by ABG analysis at baseline and after 8 weeks. A comparative analysis of variables was performed with a student t-test, considering type 1 error (α = 0.05) using SPSS 27 software.

RESULTS: The indexes included maximal inspiratory pressure (PImax) (P = 0.000) and maximal expiratory pressures PEmax (P = 0.002). The strength of breathing muscles index (S-index) (P = 0.002) had a significant increase before and after rehabilitation in both groups (P ˂ 0.05). In intergroup analysis, the only factor with a significant increase was PImax (P = 0.019).

CONCLUSION: The use of IMT, along with chest opening training and diaphragm exercises, can cause a relative improvement of the respiratory muscles' function indexes, especially PImax in ALS patients. More clinical trials are required.}, } @article {pmid40740433, year = {2025}, author = {Shahim, P and AlQahtani, A and Kokkinis, AD and Kazmi, N and Ezuma-Ngwu, M and Misra, J and Harmison, G and Benoit, N and Jones, M and Howe, E and Schindler, AB and Joe, GO and Grunseich, C}, title = {CSF and blood neuronal injury biomarkers in spinal bulbar muscular atrophy and amyotrophic lateral sclerosis 4.}, journal = {Brain communications}, volume = {7}, number = {4}, pages = {fcaf275}, pmid = {40740433}, issn = {2632-1297}, abstract = {Spinal and bulbar muscular atrophy (SBMA) and amyotrophic lateral sclerosis 4 (ALS4) are two forms of motor neuron disease characterized by clinically slow disease progression. Based on the current limited human studies, the contribution of central nervous neurodegeneration to these diseases and the rate of clinical progression is unclear. Neuronal proteins glial fibrillary acidic protein (GFAP), neurofilament light (NfL) chain, or Total-tau measured in either cerebrospinal fluid or blood could serve as sensitive markers of neurodegeneration. We studied 56 adult participants (32 SBMA, 7 ALS4, and 17 controls) who were enrolled at the National Institutes of Health, of whom 22 (10 SBMA, 7 ALS4, and 5 controls) underwent paired CSF and serum sampling, and of whom 6 participants were assessed longitudinally up to 24 months from initial visit. An additional 7 controls completed CSF sampling only. CSF GFAP, NfL chain, and Total-tau correlated with corresponding levels in serum (r = 0.74, r = 0.47, and r = 0.70, respectively). CSF GFAP was increased in patients with SBMA (median, 8840 pg/mL, interquartile range (IQR) 5780-10489) as compared to controls (median, 5315 pg/mL, IQR 1822-6657; P = 0.029) but not compared with ALS4 (median, 5015 pg/mL, IQR 3172-9803; P = 0.31). Patients with SBMA had increased concentrations of CSF NfL chain (median, 719 pg/mL, IQR 483-773) as compared to ALS4 (median, 307 pg/mL, IQR 187-629; P = 0.034) or controls (median, 395 pg/mL, IQR 307-497; P = 0.024). In contrast, serum concentrations of either biomarker did not differ significantly between SBMA, ALS4, or controls. Higher CSF GFAP and NfL chain levels were associated with lower SBMA Functional Rating Scale scores (r = -0.49 and r = -0.42, respectively). Over the course of 24 months, the average change in SBMA Functional Rating Scale was -0.83 points, while the changes in CSF GFAP and NfL chain were progressive (increased 1.4-fold and 1.3-fold, respectively). Our data suggest that SBMA patients have increased concentrations of CSF GFAP and NfL chain as compared to ALS4 and controls, and higher levels of these biomarkers are associated with disease severity. Importantly, these results indicate that SBMA is associated with progressive neurodegeneration and that either CSF GFAP or NfL chain may be useful for patient stratification and monitoring treatment effects in clinical trials.}, } @article {pmid40740123, year = {2025}, author = {Giacomelli, E and Scirocco, E and Higgins, M and Pilja, A and Paganoni, S and Ho, D}, title = {Research access barriers in amyotrophic lateral sclerosis.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {}, number = {}, pages = {1-8}, doi = {10.1080/21678421.2025.2539900}, pmid = {40740123}, issn = {2167-9223}, abstract = {As the general population ages, amyotrophic lateral sclerosis (ALS) incidence and prevalence are expected to rise, and the barriers that limit participation in ALS clinical research studies may increase. In this report, we highlight key challenges and available resources for accessing clinical research. We emphasize the importance of education and engagement among individuals with ALS and their families, clinicians, and researchers. Addressing accessibility and fostering trust in ALS research participation is essential to advance treatments for this devastating disease. We propose practical strategies to overcome participation barriers, including decentralized trial models, remote participation options, and expanded outreach through patient navigators, advisory committees, and digital tools. Strengthening partnerships among individuals with ALS, caregivers, researchers, ALS organizations, regulators, and industry, will help align research efforts with community needs and accelerate therapeutic development.}, } @article {pmid40740086, year = {2025}, author = {Ghazali, L and Hamid, SSA and Mohamad, H and Aziz, A}, title = {Clinical review of laryngomalacia in a tertiary hospital.}, journal = {The Medical journal of Malaysia}, volume = {80}, number = {4}, pages = {443-447}, pmid = {40740086}, issn = {0300-5283}, mesh = {Humans ; *Laryngomalacia/diagnosis/epidemiology/therapy/classification ; Male ; Female ; Retrospective Studies ; Tertiary Care Centers ; Infant ; Severity of Illness Index ; Infant, Newborn ; }, abstract = {INTRODUCTION: Laryngomalacia is the most common cause of stridor in infants, with severity ranging from mild to severe forms. Accurate classifications of severity is essential for guiding management and improving outcomes.

MATERIAL AND METHODS: We conducted a retrospective study of paediatric patients under two years of age diagnosed with laryngomalacia at a tertiary referral centre between January 2010 and December 2020. Data collected included demographic details, clinical presentation, comorbidities, endoscopic findings, treatment, and follow-up duration. Severity was classified using a symptoms-based scoring system by Shah et al, while laryngomalacia types were determined according to Olney et al's endoscopic classification. Association between severity, endoscopic findings, comorbidities and treatment choice were analysed using logistic regression.

RESULTS: A total of 148 patients were included (59.49% male). Mild, moderate, and severe laryngomalacia were observed in 45.27%, 35.14%, and 19.59% of patients, respectively. Type 3 laryngomalacia, identified via endoscopy, was significantly associated with severe disease (p<0.001). Comorbidities, particularly gastroesophageal reflux disease, cardiac, pulmonary, syndromic, neurological conditions and synchronous airway lesions, were significantly linked to higher severity (p<0.05). A strong association was found between severity and treatment: moderate cases had 89.6 times, and severe cases 133.3 times, the odds of receiving surgical intervention compared to mild cases (p<0.001).

CONCLUSION: Mild laryngomalacia was most prevalent, but severity increased with specific comorbidities and endoscopic findings. Objective symptom scoring and endoscopic classification are valuable for assessing severity and guiding appropriate management in laryngomalacia.}, } @article {pmid40739673, year = {2025}, author = {Zheng, X and Yuan, W and Li, L and Ma, H and Zhu, M and Li, X and Feng, X}, title = {Targeting proprotein convertase subtilisin/kexin type 9 (PCSK9) to tackle central nervous system diseases: role as a promising approach.}, journal = {European journal of medical research}, volume = {30}, number = {1}, pages = {690}, pmid = {40739673}, issn = {2047-783X}, mesh = {Humans ; *Proprotein Convertase 9/metabolism/genetics ; *PCSK9 Inhibitors/therapeutic use ; *Central Nervous System Diseases/drug therapy/metabolism ; Animals ; }, abstract = {Atherosclerosis-associated disease (ASD) represents a complex pathological condition, characterized by the formation of atherosclerotic plaques within the arterial walls, encompassing cholesterol depositions, which is primarily attributed to elevated levels of low-density lipoprotein-cholesterol (LDL-C). A log-linear association between the absolute magnitude of LDL-C exposure and ASD risk has been widely studied. High levels of LDL-C have been acknowledged as the predominant culprit. The previous research findings have demonstrated that PCSK9 inhibitors (PCSK9i) can remarkably diminish the risk of ASD. The current research has primarily focused on the relevance of PCSK9 to the cardiovascular system and lipid metabolism; however, an increasing body of evidence shows that PCSK9 is pivotal in pathogenic processes in other organ systems. Yet, PCSK9's impact on the brain is complex and not fully clarified, although several recent studies emphasize a putative role of its impact on various neurodegenerative disorders. Among neurological disorders, not only stroke but neurogenesis, neural cell differentiation, central LDL receptor metabolism, neural cell apoptosis, neuroinflammation, alcohol use disorder (AUD), amyotrophic lateral sclerosis(ALS), and Alzheimer's Disease (AD) are related to PCSK9. PCSK9 expression in brain is low but greatly upregulated in neurological disorders. Therefore, PCSK9 is a promising pathway for the treatment of central nervous diseases. This review comprehensively describes evidence from the previous research on the effects of PCSK9i on the central nervous system, with a focus on the clinical potential of PCSK9i. We anticipate that this review will generate data that will help biomedical researchers or clinical workers develop treatments for the neurological diseases based on PCSK9i.}, } @article {pmid40738791, year = {2025}, author = {Roy, A and Dawson, VL and Dawson, TM}, title = {From metabolism to mind: The expanding role of the GLP-1 receptor in neurotherapeutics.}, journal = {Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics}, volume = {}, number = {}, pages = {e00712}, doi = {10.1016/j.neurot.2025.e00712}, pmid = {40738791}, issn = {1878-7479}, abstract = {GLP-1 receptor agonists (GLP-1RAs), initially approved for diabetes and obesity, are now under investigation for neuroprotective effects in a range of neurological disorders. These agents, whose receptors are widely expressed in brain regions involved in cognition and metabolism, modulate neurotransmitter release and promote neurogenesis. While preclinical studies consistently demonstrate benefits in models of Alzheimer's disease, Parkinson's disease, multiple sclerosis, and amyotrophic lateral sclerosis (ALS), clinical trial outcomes have been variable, largely owing to heterogeneity in study populations and trial design. Newer agents, such as NLY01 and tirzepatide, are under development to enhance central nervous system penetration and efficacy. Although GLP-1RAs are generally safe in metabolic conditions, their use in neurological diseases requires careful monitoring and patient selection. Future directions include developing reliable biomarkers, implementing precision medicine strategies, and exploring the use of combination therapies to maximize therapeutic potential.}, } @article {pmid40737511, year = {2025}, author = {Turner, MR}, title = {Inverting the logic in amyotrophic lateral sclerosis.}, journal = {Brain : a journal of neurology}, volume = {}, number = {}, pages = {}, doi = {10.1093/brain/awaf276}, pmid = {40737511}, issn = {1460-2156}, } @article {pmid40737092, year = {2025}, author = {Dargan, R and Mikheenko, A and Johnson, NL and Packer, BE and Li, Z and Craig, EJ and Como, CN and Sarbanes, SL and Bereda, C and Hao, Y and Mehta, PR and Keuss, M and Nalls, MA and Qi, YA and Weller, CA and Fratta, P and Ryan, VH}, title = {Altered mRNA transport and local translation in i3Neurons with RNA-binding protein knockdown.}, journal = {Nucleic acids research}, volume = {53}, number = {14}, pages = {}, pmid = {40737092}, issn = {1362-4962}, support = {/AG/NIA NIH HHS/United States ; Fi2GM142475/GM/NIGMS NIH HHS/United States ; ZIAAG000547/HH/HHS/United States ; /NH/NIH HHS/United States ; ZIAAG000534/HH/HHS/United States ; /NS/NINDS NIH HHS/United States ; Fi2GM146657/GM/NIGMS NIH HHS/United States ; ZIA AG000534/ImNIH/Intramural NIH HHS/United States ; ZIA AG000547/ImNIH/Intramural NIH HHS/United States ; //Center for Alzheimer's and Related Dementias/ ; }, mesh = {*RNA, Messenger/metabolism/genetics ; *Protein Biosynthesis ; Humans ; *RNA-Binding Proteins/genetics/metabolism ; *DNA-Binding Proteins/genetics/metabolism ; *RNA Transport ; Gene Knockdown Techniques ; Heterogeneous Nuclear Ribonucleoprotein A1/genetics ; Induced Pluripotent Stem Cells/metabolism/cytology ; *Neurons/metabolism ; Heterogeneous-Nuclear Ribonucleoprotein Group A-B/genetics/metabolism ; Neurites/metabolism ; Amyotrophic Lateral Sclerosis/genetics/metabolism ; Transcriptome ; Frontotemporal Dementia/genetics/metabolism ; }, abstract = {Neurons rely on messenger RNA (mRNA) transport and local translation to facilitate rapid protein synthesis in processes far from the cell body. These processes allow precise spatial and temporal control of translation and are mediated by RNA-binding proteins (RBPs), including those associated with neurodegenerative diseases. Here, we use proteomics, transcriptomics, and microscopy to investigate the impact of RBP depletion on mRNA transport and local translation in induced pluripotent stem cell-derived neurons. We find thousands of transcripts enriched in neurites and that many of these transcripts are locally translated, possibly due to the shorter length of transcripts in neurites. Loss of frontotemporal dementia/amyotrophic lateral sclerosis (FTD/ALS)-associated RBPs TDP-43 and hnRNPA1 induce distinct alterations in the neuritic proteome and transcriptome. TDP-43 knockdown (KD) leads to slightly increased neuritic mRNA and translation, while hnRNPA1 loss has more moderate effects on local mRNA profiles, possibly due to compensation by hnRNPA3. These results highlight the crucial role of FTD/ALS-associated RBPs in mRNA transport and local translation in neurons and the importance of these processes in neuron health and disease.}, } @article {pmid40736930, year = {2025}, author = {Chen, X and Zhuang, J and Chen, Z and Liu, S and Xu, Y and Chen, C and Yi, J and Yu, F and Xie, B and He, F}, title = {The relationship between allostatic load levels and time to deterioration of health-related quality of life in non-small cell lung cancer patients.}, journal = {Journal of cancer survivorship : research and practice}, volume = {}, number = {}, pages = {}, pmid = {40736930}, issn = {1932-2267}, support = {grant number 2023J01093//Fujian Provincial Natural Science Foundation Project/ ; }, abstract = {BACKGROUND AND PURPOSE: Allostatic load (AL) significantly impacts patient outcomes. This study aimed to explore the association between AL levels and time to deterioration (TTD) of health-related quality of life (HRQoL) in non-small cell lung cancer (NSCLC) patients.

METHODS: A prospective study (May 2017-September 2022) included 362 NSCLC patients from The First Affiliated Hospital of Fujian Medical University. HRQoL was assessed using EORTC QLQ-C30 and EORTC QLQ-LC13 questionnaires, and AL-related biomarkers were collected. Univariate and multivariate Cox regression analyses evaluated the impact of AL on HRQoL TTD.

RESULTS: TTD events were most common in global health status (QL), physical functioning (PF), and dyspnea (LC-DY). Lower AL levels delayed TTD in emotional functioning (EF) (HR = 2.041, 95% CI: 1.404-2.969, P < 0.001), cognitive functioning (CF) (HR = 1.613, 95% CI: 1.082-2.403, P = 0.019), insomnia (SL) (HR = 1.553, 95% CI: 1.064-2.266, P = 0.022), constipation (CO) (HR = 2.114, 95% CI: 1.179-3.791, P = 0.012), and hemoptysis (LC-HA) (HR = 2.316, 95% CI: 1.037-5.172, P = 0.041). Multivariate analysis confirmed these findings, except for insomnia, which lost significance.

CONCLUSIONS: Lower AL levels delayed TTD in EF, CF, CO, and LC-HA, highlighting AL's role in preserving HRQoL in NSCLC patients.

HRQoL is critical for cancer survivors. This study underscores the importance of AL to improve HRQoL outcomes in NSCLC patients.}, } @article {pmid40736059, year = {2025}, author = {Zhao, Q and Zhao, Z and Zhao, G and Xue, L and Chen, L and Zhou, G and Liang, J and Qin, M and Hu, M}, title = {Effect of Defocus Incorporated Multiple Segments (Fog Vision +0.50 D) Combined With 0.01% Atropine on the Preclinical and Early Stages of Myopia in Children.}, journal = {Journal of pediatric ophthalmology and strabismus}, volume = {}, number = {}, pages = {1-12}, doi = {10.3928/01913913-20250530-04}, pmid = {40736059}, issn = {1938-2405}, abstract = {PURPOSE: To retrospectively analyze the efficacy of multi-zone positive optical defocus lenses (DIMS) + fog vision + 0.01% atropine for the treatment of children with preclinical and early stages of myopia.

METHODS: The axial length (AL) and refraction were analyzed at baseline and after 12 months of follow-up in 192 eyes treated with combined therapy. The success of treatment was defined as an annual AL growth rate within the physiological growth range and myopia progression of -0.50 diopters (D)/year or greater. Subgroup analysis was performed to investigate the percentage of treatment success in the overall population compared to the subgroups based on baseline AL and age.

RESULTS: Overall, the success rates were 87% and 93% for AL control and myopia control, respectively. Compared to before combined therapy, there was an increase in AL after treatment (boys: P < .001; girls: P < .001). The change in spherical equivalent (SE) was consistent with the change in AL, with both boys and girls showing an increase in SE after treatment, with a statistically significant difference in girls (boys: P = .059; girls: P = .001). There was no statistically significant difference in the percentage of treatment success in either boys or girls based on baseline AL and age subgroups compared to the overall population.

CONCLUSIONS: The treatment regimen of DIMS + fog vision + 0.01% atropine demonstrated significant control effects on myopia in preclinical and early stages of myopia in children across different genders, baseline ALs, and ages. Timely intervention is recommended once a tendency toward myopia is observed in children.}, } @article {pmid40735987, year = {2025}, author = {Ergin, AD}, title = {Nanotechnological Approaches for Mitochondrial Targeting in Neurodegenerative Diseases.}, journal = {Current topics in medicinal chemistry}, volume = {}, number = {}, pages = {}, doi = {10.2174/0115680266397447250723073446}, pmid = {40735987}, issn = {1873-4294}, abstract = {OBJECTIVES: Mitochondria are dynamic organelles essential for energy metabolism and cellular homeostasis, playing critical roles in ATP production, calcium regulation, redox balance, and apoptosis. However, mitochondrial dysfunction is a central factor in the pathogenesis of neurodegenerative diseases, including Alzheimer's disease, amyotrophic lateral sclerosis, Huntington's disease, and Parkinson's disease. Given the essential role of mitochondria in neuronal survival, targeted therapeutic strategies that restore mitochondrial function have gained significant attention. This review explores the latest advances in mitochondrial-targeted therapies and their potential applications in neurodegenerative diseases.

METHODS: A comprehensive literature review was conducted on mitochondrial-targeted therapeutic strategies, with a focus on nanotechnology-based drug delivery systems. The analysis includes various nanoparticle-based approaches, such as liposomes, DQAsomes, and polymeric nanoparticles, which have demonstrated high biocompatibility, controlled drug release, and enhanced mitochondrial targeting efficiency. Additionally, mitochondria-penetrating peptides and delocalized lipophilic cations (DLCs) are discussed for their role in improving drug localization within mitochondria and overcoming biological barriers, including the blood-brain barrier (BBB).

RESULTS: Recent research shows the potential of mitochondrial-targeted antioxidants, peptides, and biocompatible nanocarriers in arranging mitochondrial dysfunction and protecting neurons from oxidative damage. Various nanoparticle-based drug delivery systems have demonstrated the ability to selectively target mitochondria, improving drug bioavailability, therapeutic efficacy, and neuroprotective outcomes in neurodegenerative diseases.

CONCLUSION: Mitochondria-targeted therapies provide promising avenues for disease-modifying treatments aimed at preserving neuronal integrity and delaying disease progression. The unique properties of nanoparticles, such as their ability to enhance drug stability, facilitate controlled release, and achieve precise mitochondrial localization, make them valuable tools for neurodegenerative disease therapy. Future research should focus on optimizing delivery systems, validating clinical applicability, and exploring interdisciplinary approaches to accelerate translation into effective treatments.}, } @article {pmid40735897, year = {2025}, author = {Leonardo, C and Bjorling, A and Chadwick, KA}, title = {Factors Associated With Type 1 Thyroplasty Revision: Insights From the TriNetX Database.}, journal = {The Laryngoscope}, volume = {}, number = {}, pages = {}, doi = {10.1002/lary.32478}, pmid = {40735897}, issn = {1531-4995}, abstract = {OBJECTIVES: Type 1 thyroplasty (T1T), or medialization laryngoplasty (ML), is a laryngeal framework surgery that corrects glottic insufficiency. Prior studies report revision rates of T1T from 5% to 40%, but factors influencing the need for revision have not been studied in detail. The objectives of this study were to determine the revision rate of T1T and identify patient factors associated with revision.

METHODS: Retrospective cohort study. Patients undergoing T1T (CPT 31591) were identified in TriNetX, a global collaborative network with data from over 128 million patients. The revision rate was determined by the percentage of patients undergoing a second T1T at least 30 days after the initial procedure. Patient factors (demographics, surgical history, and comorbidities) were compared between groups.

RESULTS: A total of 4029 patients underwent T1T; 323 (8.02%) patients underwent revision T1T. Patients undergoing revision were slightly older at initial surgery compared to those not requiring revision (63.5 vs. 61.2 years, p = 0.02), and more likely to be of White or American Native race. Comorbidities associated with revision include pulmonary diseases, neurological conditions, and mental health disorders. A history of thyroidectomy or tracheostomy was also associated with revision. Gender, geographic region, tobacco use, emphysema, Parkinson's disease, and amyotrophic lateral sclerosis were not associated with the need for revision T1T.

CONCLUSION: This is the first comprehensive analysis of factors associated with revision T1T using the TriNetX database. Certain demographic and patient factors may influence the likelihood of requiring revision T1T, potentially impacting patient selection and providing a basis for individualized preoperative patient counseling.

LEVEL OF EVIDENCE: Level III.}, } @article {pmid40735390, year = {2025}, author = {Liu, Y and Chen, G and Li, M and Li, M and Xie, D and Luo, Z}, title = {Development of long-acting riluzole transdermal patch against amyotrophic lateral sclerosis: Mechanistic insights into polyglyceryl-3 dioleate-enhanced drug release and skin permeation.}, journal = {International journal of pharmaceutics: X}, volume = {10}, number = {}, pages = {100363}, pmid = {40735390}, issn = {2590-1567}, abstract = {Patients with amyotrophic lateral sclerosis (ALS) often experience difficulty swallowing, making oral administration unsuitable for effective treatment. A transdermal drug delivery system (TDDS) offers a long-acting, non-invasive alternative for ALS therapy. In this study, a riluzole transdermal patch capable of sustained release over 72 h was developed. In vitro skin permeation and pharmacokinetic experiments were conducted to evaluate the impact of various factors-including drug loading, type and concentration of chemical penetration enhancers (CPEs), and type of pressure-sensitive adhesive-on riluzole absorption through the skin. The optimized patch formulation contained 17 % (w/w) riluzole and 10 % (w/w) polyglyceryl-3 dioleate (PGD), with an adhesive layer thickness of 111 μm. The final prescription penetration rate of riluzole was found to be 2.96 μg/(h·cm[2]). Optimized formulation displayed enhanced stability and prolonged pharmacokinetic performance (C max = 74.34 ± 13.62 ng/mL, MRT0-t = 34.91 ± 11.31 h). No significant skin irritation was observed. The role of PGD in the in vitro release and in vivo transdermal absorption of riluzole was thoroughly investigated. The results revealed that PGD not only reduced the interaction between riluzole and the pressure-sensitive adhesive, enhancing drug release but also increased the fluidity of skin lipids, leading to improved transdermal absorption. This study provides a comprehensive molecular-level understanding of PGD's effect on riluzole permeation, offering valuable insights for the rational selection of CPEs in the development of riluzole TDDS.}, } @article {pmid40733876, year = {2025}, author = {Wang, Q and Liu, Y and Zou, G and Liang, Z and Liu, H and Yang, BR and Qin, Z}, title = {Modeling light propagation for under-display sensing in a smartphone.}, journal = {Optics express}, volume = {33}, number = {15}, pages = {30847-30858}, doi = {10.1364/OE.565761}, pmid = {40733876}, issn = {1094-4087}, abstract = {Under-display sensing (UDS) is essential to achieve bezel-less smartphones (infinity display). However, light penetrating or reflected by the display panel is distorted, deteriorating UDS signals. Therefore, light propagation should be accurately modeled to analyze and optimize UDS. This study proposes a universal model that recognizes the light propagation mode using the Fresnel number. Under-display ambient light sensors (ALS), under-display cameras (UDC), and proximity sensors are identified to work in the geometric optics, Fraunhofer diffraction, and Fresnel diffraction regimes, respectively. A commercial smartphone is adopted to demonstrate the model's effectiveness and provide domain knowledge. First, regarding the angular response attenuation in under-display ALS, the geometric obstruction by the pixel layout is simulated after acquiring the display panel's microphotograph. Measured data agrees with the simulation with an error smaller than 10 degrees in the viewing angle's full width at half maximum. Next, the UDC is simulated using Fraunhofer diffraction to provide full-color pictures containing blurring caused by the pixel layout's diffraction, showing high similarity with photographs. Finally, Fresnel diffraction dominates the under-display proximity sensor, which utilizes a weakly collimated infrared beam. An approximate solution of the signal on the detector is a scaled Fraunhofer diffraction pattern whose magnification is determined by the sensor configuration. The source-detector orientation influences the background noise (the signal level when no user is present), which is simulated and compared with experimental data, providing an optimal orientation of 45 degrees. The gap between the sensor and the display panel is also investigated through simulation and experiment, demonstrating that Fresnel diffraction is more effective than geometric optics or Fraunhofer diffraction. The proposed model with solid experimental verification on a commercial smartphone can help rationally design UDS and provide insight into the light propagation problem in smartphones.}, } @article {pmid40732891, year = {2025}, author = {Hein, ZM and Arbain, MFF and Kumar, S and Mehat, MZ and Hamid, HA and Che Ramli, MD and Che Mohd Nassir, CMN}, title = {Intermittent Fasting as a Neuroprotective Strategy: Gut-Brain Axis Modulation and Metabolic Reprogramming in Neurodegenerative Disorders.}, journal = {Nutrients}, volume = {17}, number = {14}, pages = {}, pmid = {40732891}, issn = {2072-6643}, mesh = {Humans ; *Neurodegenerative Diseases/metabolism/therapy ; *Fasting/physiology ; Gastrointestinal Microbiome/physiology ; Animals ; *Brain/metabolism ; *Brain-Gut Axis/physiology ; *Neuroprotection ; Energy Metabolism ; Brain-Derived Neurotrophic Factor/metabolism ; Metabolic Reprogramming ; Intermittent Fasting ; }, abstract = {Intermittent fasting (IF) is emerging as a heterogeneous neurometabolic intervention with the possibility of changing the course of neurodegenerative diseases. Through the modulation of the gut-brain axis (GBA), cellular bioenergetics (or metabolic) reprogramming, and involvement in preserved stress adaptation pathways, IF influences a range of physiological mechanisms, including mitobiogenesis, autophagy, circadian rhythm alignment, and neuroinflammation. This review critically synthesises current preclinical and early clinical evidence illustrating IF's capability to supplement synaptic plasticity and integrity, reduce toxic proteins (proteotoxic) burden, and rehabilitate glial and immune homeostasis across models of Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. The key players behind these effects are bioactive metabolites such as short-chain fatty acids (SCFA) and β-hydroxybutyrate (BHB), and molecular mediators such as brain-derived neurotrophic factor (BDNF). We feature the therapeutic pertinence of IF-induced changes in gut microbiota composition, immune response, and mitochondrial dynamics, and we discuss emerging approaches for merging IF into precision medicine frameworks. Crucial challenges include individual variability, protocol optimisation, safety in cognitively vulnerable populations, and the need for biomarker-guided, ethically grounded clinical trials. Finally, we propose IF as a scalable and flexible intervention that, when personalised and integrated with other modalities, may reframe neurodegeneration from a model of irreversible decline to one of modifiable resilience.}, } @article {pmid40731193, year = {2025}, author = {Turkbey, B and Schoots, IG and Haider, MA}, title = {Reply to Masatomo Kaneko, Vasileios Magoulianitis, Vinay Duddalwar, et al's Letter to the Editor re: Baris Turkbey, Henkjan Huisman, Andriy Fedorov, et al. Requirements for AI Development and Reporting for MRI Prostate Cancer Detection in Biopsy-naive Men: PI-RADS Steering Committee, Version 1.0. Radiology 2025;315:e240140.}, journal = {European urology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.eururo.2025.07.005}, pmid = {40731193}, issn = {1873-7560}, } @article {pmid40730291, year = {2025}, author = {Magdalena, R and Ferrada, L and Ramírez, E and Smith-Ghigliotto, JF and Salazar, K and Nualart, F}, title = {Dehydroascorbic acid impairs neurite growth through RIPK1-associated caspase activation.}, journal = {Free radical biology & medicine}, volume = {239}, number = {}, pages = {406-416}, doi = {10.1016/j.freeradbiomed.2025.07.036}, pmid = {40730291}, issn = {1873-4596}, abstract = {Axonal and neurite loss is a common event in neurodegenerative diseases, such as Alzheimer's disease or amyotrophic lateral sclerosis, which are enhanced by oxidative damage and reactive oxygen species (ROS) production. In the central nervous system, vitamin C can be found as ascorbic acid (AA), its reduced form, or dehydroascorbic acid (DHA), its oxidized form. Vitamin C mainly acts as an antioxidant agent, and homeostasis in the brain is maintained through its recycling between neurons and astrocytes. However, DHA accumulation under pathophysiological conditions has been associated with changes in neuronal metabolism and necroptotic cell death through RIPK1 activation. Furthermore, recent studies show that DHA accumulation induces significant neurite loss; however, it is unknown whether this effect is associated with RIPK1 activation. Here, we show that DHA treatment on neurospheres (NE) in vitro induces significant neurite shortening and reduced branching, effects associated with early RIPK1 activation and inhibited through Necrostatin-1s and zVAD-FMK treatment, suggesting the activation of apoptotic mechanisms. Finally, we propose DHA, the oxidized form of vitamin C, impairs neurite growth through ripk1-associated caspase activation.}, } @article {pmid40730054, year = {2025}, author = {Zhao, J and Bai, J and Wang, H and Zhang, Y and Zhang, J and Zhu, Y and Pang, X and Chen, Z and Ling, L and Cheng, H and Li, M and Huang, X}, title = {Diagnostic value of EMG of sternocleidomastoid and trapezius in assessing bulbar lower motor neuron involvement in amyotrophic lateral sclerosis patients.}, journal = {Journal of electromyography and kinesiology : official journal of the International Society of Electrophysiological Kinesiology}, volume = {84}, number = {}, pages = {103040}, doi = {10.1016/j.jelekin.2025.103040}, pmid = {40730054}, issn = {1873-5711}, abstract = {The diagnostic value of needle electromyography (EMG) of sternocleidomastoid (SCM) and trapezius (TRA) in assessing bulbar lower motor neuron involvement (LMN) remained controversial. 203 sporadic amyotrophic lateral sclerosis (ALS) patients were enrolled to assess the correlation between EMG abnormalities in SCM and TRA and bulbar LMN involvement. Additionally, difference analysis and diagnostic consistency analysis of EMG abnormalities in GEN (genioglossus), SCM, and TRA were compared. Finally, separate effects of EMG abnormalities in GEN, SCM, and TRA on diagnostic gradings were examined according to the Awaji-Shima criteria. 22 (18.2 %) and 65 (53.7 %) patients without bulbar LMN involvement showed EMG abnormalities in SCM and TRA. In contrast, 19 (23.2 %) and 11 (13.4 %) patients with bulbar LMN involvement showed normal EMG results in SCM and TRA. Multivariate logistic regression analyses showed that both EMG abnormalities in SCM and TRA were correlated with bulbar LMN involvement (P < 0.001). SCM showed electrophysiological characteristics similar to GEN when compared to TRA. However, TRA (67.0 %) showed significantly higher rates of EMG abnormalities than SCM (41.9 %) and GEN (40.4 %) in the whole study population. Reclassified diagnostic gradings showed no significant difference when evaluating EMG abnormalities in individual muscles to indicate bulbar LMN involvement (P = 0.072). EMG abnormalities in SCM and TRA could not fully represent bulbar LMN involvement but were correlated with it. It's advisable to prioritise TRA as a better option when a patient cannot tolerate an EMG examination in the GEN. To enhance the diagnostic evaluation, an EMG examination of GEN could be served as the last choice.}, } @article {pmid40730020, year = {2025}, author = {Martins, AP and Mattos, AHB and Pupe, CCB and Martinez, ARM and Nucci, A and França, MC}, title = {The novel missense variant D40V causes a young adult presentation of ANXA11-related myopathy.}, journal = {Neuromuscular disorders : NMD}, volume = {53}, number = {}, pages = {105443}, doi = {10.1016/j.nmd.2025.105443}, pmid = {40730020}, issn = {1873-2364}, abstract = {Pathogenic variants in the ANXA11 gene, which encodes the calcium-dependent phospholipid ligand protein Annexin A11, have been recently associated with amyotrophic lateral sclerosis, frontotemporal dementia and/or muscle disease. ANXA11-related myopathy is characterized by slowly progressive adult-onset limb-girdle weakness combined with axial and facial muscle involvement. Here we expand the spectrum of ANXA11-related myopathy with the description of a 38-year-old Brazilian woman with prominent distal and bulbar manifestations combined with dropped head caused by the novel p.D40V ANXA11 variant. This report widens both the genotypic and phenotypic spectrum of ANXA11-related myopathy. It also points to the pathophysiological relevance of amino acid changes at the highly conserved 40th Annexin A11 residue.}, } @article {pmid40728732, year = {2025}, author = {Tuddenham, JF and Fujita, M and Lee, E and Nimmagadda, N and Khairallah, A and Harbison, C and Flowers, XE and Coronas-Samano, G and Maniatis, S and Daly, A and Schneider, JA and Teich, AF and Vonsattel, JPG and Sims, PA and Elyaman, W and Bradshaw, EM and Ostrow, LW and Phatnani, H and Shneider, NA and Bennett, DA and De Jager, PL and Przedborski, S and Menon, V and Olah, M}, title = {Single-cell transcriptomic landscape of the neuroimmune compartment in amyotrophic lateral sclerosis brain and spinal cord.}, journal = {Acta neuropathologica}, volume = {150}, number = {1}, pages = {10}, pmid = {40728732}, issn = {1432-0533}, support = {R01 NS117583/NS/NINDS NIH HHS/United States ; NS107442//National Institute of Health, USA/ ; R01 NS107442/NS/NINDS NIH HHS/United States ; U01 AG061356/AG/NIA NIH HHS/United States ; P30 AG066462/AG/NIA NIH HHS/United States ; CS-02018-191971//Chan-Zuckerberg Neurodegeneration Challenge Network/ ; NS117583//National Institute of Health, USA/ ; S10 OD020056/OD/NIH HHS/United States ; P30 CA013696/CA/NCI NIH HHS/United States ; RF1 AG057473/AG/NIA NIH HHS/United States ; UL1 TR001873/TR/NCATS NIH HHS/United States ; AG057473//National Institute of Health, USA/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/immunology/pathology/genetics/metabolism ; Humans ; *Spinal Cord/immunology/metabolism/pathology ; *Microglia/metabolism/immunology ; *Transcriptome ; Single-Cell Analysis ; *Brain/immunology/metabolism/pathology ; Female ; Male ; Middle Aged ; Aged ; }, abstract = {Development of therapeutic approaches that target specific microglia responses in amyotrophic lateral sclerosis (ALS) is crucial due to the involvement of microglia in ALS progression. Our study identifies the predominant microglia subset in human ALS primary motor cortex and spinal cord as an undifferentiated phenotype with dysregulated respiratory electron transport. Moreover, we find that the interferon response microglia subset is enriched in donors with aggressive disease progression, while a previously described potentially protective microglia phenotype is depleted in ALS. Additionally, we observe an enrichment of non-microglial immune cell, mainly NK/T cells, in the ALS central nervous system, primarily in the spinal cord. These findings pave the way for the development of microglia subset-specific therapeutic interventions to slow or even stop ALS progression.}, } @article {pmid40728364, year = {2025}, author = {Wang, M and Guo, X and Zhang, H and Zhang, N and Yin, T and Gao, Y and Kang, J and Hu, Y and Fan, D and Ye, S}, title = {Educational adjustments for the Chinese version of the Edinburgh Cognitive and Behavioral Screen (ECAS): establishing normative data.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {}, number = {}, pages = {1-7}, doi = {10.1080/21678421.2025.2539904}, pmid = {40728364}, issn = {2167-9223}, abstract = {BACKGROUND: The Edinburgh Cognitive and Behavioral ALS Screen (ECAS) is a cognitive screening tool designed for patients with amyotrophic lateral sclerosis (ALS). It has been translated into various languages and used globally. This study aimed to establish normative data for the Chinese version of the ECAS to better serve the Mandarin population.

METHODS: We enrolled 358 healthy individuals from different regions of China, all of whom completed the ECAS, and 340 also completed the Mini-Mental State Examination (MMSE). The participants were categorized into six age groups and five education groups.

RESULTS: ECAS scores were found to be related to education level (p < 0.001). After Bonferroni correction for multiple comparisons, we determined that there were no significant differences in total ECAS scores between the junior middle school and senior middle school groups, leading to their combination into a single middle school group. We established cutoff values for the ECAS on the basis of education group. After adjusting for age, sex, and education level, a significant correlation was found between MMSE scores and total ECAS scores (p < 0.001), indicating a high level of consistency in the cognitive assessment.

CONCLUSION: We have established norms for the ECAS on the basis of education level, and the ECAS is highly consistent with the MMSE in the assessment of cognition. These norms will be instrumental in future clinical and follow-up work for Mandarin ALS patients.}, } @article {pmid40727601, year = {2025}, author = {Termkijwanich, P and Sanguanwit, P and Yuksen, C and Trakulsrichai, S and Sricharoen, P}, title = {Different Resuscitation Termination Criteria for Out of Hospital Cardiac Arrest; A Prognostic Accuracy Study.}, journal = {Archives of academic emergency medicine}, volume = {13}, number = {1}, pages = {e59}, pmid = {40727601}, issn = {2645-4904}, abstract = {INTRODUCTION: Termination of resuscitation (TOR) rules in out of hospital cardiac arrest (OHCA) varies across different healthcare settings and populations. This study aimed to externally validate ten TOR rules for predicting death before hospital admission among OHCA patients.

METHODS: A retrospective prognostic accuracy study analyzed 379 non-trauma OHCA patients (≥18 years) in Bangkok who were either treated by the emergency medical services (EMS) of Ramathibodi Hospital or transported to Ramathibodi's emergency department by another EMS provider (January 2010 - March 2023). The predictive performance of ten TOR rules (AHA-BLS, AHA-ALS, Korean Cardiac Arrest Research Consortium (KoCARC) rules I, II, and III, Goto's rule, Shihabashi's rule, the New Model I, Helsinki's, and Petrie's rule) in predicting death before hospital admission as well as false positive rates (FPRs) of rules at various resuscitation times were calculated and reported with 95% confidence interval (CI).

RESULTS: Among 379 OHCA patients, 308 (81.27%) died before hospital admission and 71 (18.73%) survived to discharge. The New model I demonstrated the most conservative predictive performance with sensitivity of 96.7% (95% CI: 93.0-98.8), NPV of 91.5% (95% CI: 82.5-96.8), and area under the curve (AUC) of 0.74 (95% CI: 0.70-0.79). The KoCARC III showed FPR of 2.8%. Based on the initial presenting criteria, the FPR varied at different resuscitation time points, with increasing FPR over 30 minutes. Among all rules, Helsinki's and AHA-BLS showed the highest FPRs (1.14 - 21.13 and 1.14 - 23.94, respectively) while the KoCARC TOR rules III demonstrated the most conservative consistency in maintaining a low FPR (0-2.82%) throughout time.

CONCLUSION: The KoCARC III demonstrated relatively high safety for TOR decisions in Bangkok's OHCA population, with the lowest FPR, and high sensitivity and NPV. TOR rules showed higher FPRs compared to previous studies. These findings should be interpreted with caution due to the retrospective design, potential selection bias, and EMS protocol changes over the 10-year study period.}, } @article {pmid40727259, year = {2025}, author = {Sun, W and Zhu, A and Chang, H and Xia, J and Gao, J and Zhang, Z and Chi, F and Zhu, Y and Bao, X}, title = {Causal associations and shared genetic etiology between neurodegenerative diseases and constipation.}, journal = {Journal of Alzheimer's disease reports}, volume = {9}, number = {}, pages = {25424823251362469}, pmid = {40727259}, issn = {2542-4823}, abstract = {BACKGROUND: There is increasing evidence suggesting a correlation between neurodegenerative diseases (NDDs) and constipation; however, their genetic relationship and causal mechanisms remain inadequately elucidated.

OBJECTIVE: We aim to investigate the causal link and shared genetic basis between NDDs and constipation.

METHODS: We obtained summary statistics from large-scale genome-wide association studies, encompassing five NDDs, including Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), Lewy body dementia (LBD), as well as constipation. The primary analysis employed five Mendelian randomization methods to evaluate causal effects, while linkage disequilibrium score regression (LDSC) and high-definition likelihood (HDL) were utilized to investigate genetic correlations. Additionally, significant pleiotropic SNPs were identified using pleiotropic analysis under the composite null hypothesis (PLACO) and functional mapping and annotation (FUMA). Finally, enrichment analysis was conducted to explore the biological pathways associated with the identified pleiotropic genes.

RESULTS: MR analysis revealed a significant causal relationship between AD and an enhanced risk of constipation was demonstrated (OR = 1.043, 95% CI: 1.015-1.073, p = 0.003), while no causality was found between PD, MS, ALS, LBD, and the risk of constipation (p > 0.05). LDSC and HDL analysis revealed a significant positive genetic correlation between AD and constipation. Using PLACO combined with FUMA, we identified 30 overlapping pleiotropic loci, with pathway enrichment analysis revealing important biological pathways related to Aβ metabolism and processing, tau protein process, and the complement and coagulation cascades.

CONCLUSIONS: Our study indicates that AD is a contributing factor to constipation and uncovers the complex genetic mechanisms linking AD and constipation, which holds significant implications for diagnosis and treatment of both conditions.}, } @article {pmid40726766, year = {2025}, author = {Bingham, IN and Norel, R and Roitberg, EG and Peller, J and Trevisan, MA and Agurto, C and Merler, M and Shalom, DE and Aguirre, F and Embon, I and Taitz, A and Harris, D and Wright, A and Seaver, K and Sullivan, S and Green, JR and Ostrow, LW and Fraenkel, E and Berry, JD}, title = {Listener effort measures clinically meaningful change of dysarthria in amyotrophic lateral sclerosis.}, journal = {Brain communications}, volume = {7}, number = {4}, pages = {fcaf232}, pmid = {40726766}, issn = {2632-1297}, support = {K24 DC016312/DC/NIDCD NIH HHS/United States ; R42 DC019877/DC/NIDCD NIH HHS/United States ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative motor neuron disease that can cause progressive bulbar dysfunction and dysarthria, resulting in reduced quality of life. Quantitative motor speech analysis can identify features of dysarthria that worsen with ALS progression but are not, inherently, clinically meaningful. Listener effort (LE) is a clinician-rated feature describing how much effort the listener needs to exert to understand the dysarthric speaker. This study investigated whether LE could act as a clinically meaningful measure of ALS dysarthria that could be used as an outcome measure in clinical trials. The Everything ALS Speech Study obtained longitudinal clinical information and speech recordings from 292 participants. In a subset of 125 participants, we measured speaking rate and three speech-language pathologists (SLPs) with expertise in ALS rated LE. We also built and tested a LE prediction algorithm to predict the SLPs' rating of LE. In addition, all speech recordings and associated clinical data are now being made available to ALS researchers via the Everything ALS portal. LE intra- and inter-rater reliability was very high (ICC 0.94-0.95). LE correlated with other measures of dysarthria at baseline and changed over time in participants with ALS (slope 0.77 pts/month, SE = 0.15, P < 0.001) but not controls (slope 0.005 pts/month, SE = 0.02, P = 0.807). The slope of LE progression was faster in people with bulbar onset than non-bulbar onset ALS (1.66 points/month versus 0.42 pts/month; P < 0.001) but was similar in all participants who had bulbar dysfunction at baseline, regardless of ALS site of onset (1.52 pts/month for bulbar onset versus 0.98 pts/month for non-bulbar onset with current bulbar involvement; P = 0.36). The LE prediction model predicted the true LE, with an average R [2] of 0.83 ± 0.07. Dysarthria is associated with decreased quality of life in people with ALS. Quantitative measures of dysarthria in ALS could be useful as ALS clinical trial outcome measures, providing insight into the progression of bulbar symptoms. Speaking rate quantifies progression but is variable across speaking stimuli, emotional states and contextual factors. LE is more inherently clinically meaningful, can be measured reliably by SLPs, changes quantitatively over time and is highly reproducible, thus may be useful as a clinical outcome assessment for ALS clinical trials. Furthermore, a LE prediction model is effective at predicting LE scores and should be validated on an external dataset.}, } @article {pmid40726565, year = {2025}, author = {Dukic, S and Govaarts, R and Hillebrand, A and de Visser, M and Seeck, M and McMackin, R}, title = {Novel approaches to EEG and MEG in motor neurone disease: IFCN Handbook Chapter.}, journal = {Clinical neurophysiology practice}, volume = {10}, number = {}, pages = {301-315}, pmid = {40726565}, issn = {2467-981X}, abstract = {Motor neurone diseases (MNDs) are increasingly being acknowledged as network disorders, with cortical dysfunction and degeneration extending beyond the motor cortex. Measures of this broader cortical pathophysiology are providing promising candidates in the search for diagnostic and prognostic biomarkers of the MNDs. Electroencephalography (EEG) and magnetoencephalography (MEG) offer a direct view of neural network activity by detecting changes in electromagnetic fields of the brain. Measurements based on EEG/MEG have often been overlooked in the search for MND biomarkers, largely due to their limited spatial resolution and the perceived challenges associated with noise in these signals. However, with recent developments in sensor technology and source reconstruction algorithms, alongside substantial improvement in pipelines that address noise, EEG/MEG-based measures can now be readily employed for spatiotemporally-precise, economical and non-invasive characterisation of cortical network pathophysiology in MNDs. Here, we provide an overview of how EEG/MEG signals have been employed to quantify neural network function in MND. We outline the advantages and limitations of these measurements, discuss the most clinically promising EEG/MEG studies of MNDs to date, and highlight future directions warranted to harness the full potential of these technologies for understanding and assessing MNDs.}, } @article {pmid40726139, year = {2025}, author = {Jin, X and Wang, X and Zheng, D and Yuan, P and Li, J and Qiu, T and Zhang, H and Chen, Y and Zhang, J and Wu, F and Liu, Q and Grecucci, A and Zhang, Y and Wang, J and Yi, X and Palaniyappan, L and Braden, BB}, title = {Disrupted Glucose Metabolism Covariance Network in Amyotrophic Lateral Sclerosis.}, journal = {CNS neuroscience & therapeutics}, volume = {31}, number = {7}, pages = {e70537}, pmid = {40726139}, issn = {1755-5949}, support = {U22A20377//National Natural Science Foundation of China/ ; 2024PT5109//The Scientific Research Program of FuRong Laboratory/ ; 2022LNJJ09//Project Program of National Clinical Research Center for Geriatric Disorders/ ; 2024ZZTS0954//Fundamental Research Funds for the Central Universities of Central South University/ ; CB-C2022//Fonds de Recherche du Québec - Santé/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism/diagnostic imaging ; Female ; Male ; Middle Aged ; Aged ; *Glucose/metabolism ; Positron-Emission Tomography ; Fluorodeoxyglucose F18 ; *Nerve Net/metabolism/diagnostic imaging ; Disease Progression ; Adult ; *Brain/metabolism/diagnostic imaging ; }, abstract = {AIMS: This study aimed to characterize the topological changes in glucose metabolism covariance networks in amyotrophic lateral sclerosis (ALS).

METHODS: We assessed the interregional coordination of [18]F-FDG-PET data to examine topological alterations in individualized glucose metabolism covariance networks in 127 ALS patients compared to 128 healthy controls (HC).

RESULTS: Compared to HC, ALS patients showed reduced small-worldness (lower normalized clustering coefficient, higher normalized characteristic path length) and decreased global and local efficiency, suggesting impaired global integration and local segregation. These network metrics correlated with disease progression and motor function. Regionally, altered degree centrality affected motor and default mode networks, and related to GABAa and mGluR5 receptor expression. Transcriptomic associations further linked these changes to immune function, synaptic signaling, and protein regulation. Bidirectional shifts in connectivity strength were observed, with both increased connectivity and disease progression independently predicting reduced survival.

CONCLUSION: Our findings may provide valuable biomarkers for monitoring the progression of ALS and suggest potential mechanistic pathways for the development of innovative therapeutic strategies for this disorder.}, } @article {pmid40725930, year = {2025}, author = {He, Y and Ming, W and Tan, Y and Wang, Y and Wang, M and Li, H and Jiao, Z and Hou, Y}, title = {The effectiveness of cognitive behavioral therapy in patients with motor neuron disease: A systematic review.}, journal = {Medicine}, volume = {104}, number = {30}, pages = {e43597}, pmid = {40725930}, issn = {1536-5964}, mesh = {Humans ; *Cognitive Behavioral Therapy/methods ; *Motor Neuron Disease/psychology/therapy ; Quality of Life ; Caregivers/psychology ; Anxiety/therapy/etiology ; Depression/therapy/etiology ; Treatment Outcome ; }, abstract = {BACKGROUND: Motor neuron disease (MND) is a neurodegenerative disorder that causes progressive loss of motor function. With limited disease-modifying drug therapies, cognitive behavioral therapy (CBT) has emerged as a key nonpharmacological intervention. This systematic review evaluated CBT's therapeutic potential across clinical domains to inform psychosocial care of patients with MND.

METHODS: Comprehensive searches were performed in PubMed, Web of Science, Cochrane Library, and Embase, from inception until February 2025. Two researchers independently screened the literature, extracted data, assessed study quality, and resolved disagreements via consensus or third-party consultation.

RESULTS: Five studies involving 561 patients were included. Compared with conventional care, CBT significantly improves patients' quality of life and psychological flexibility. However, the effects on caregiver burden and physical health were not statistically significant. CBT modalities included acceptance and commitment therapy, dialectical behavior therapy, rational-emotive behavior therapy, mindfulness cognitive therapy, and metacognitive training. Traditional CBT demonstrated superior efficacy in reducing anxiety and depression compared to acceptance and commitment therapy.

CONCLUSION: CBT effectively enhances psychological flexibility and quality of life and reduces anxiety and depression in patients with MND. The standardization of outcome measures requires improvement. High-quality randomized controlled trials are needed to further assess CBT's impact of CBT on caregiver burden and patients' physical health.}, } @article {pmid40725270, year = {2025}, author = {Tahri, A and Niccolai, E and Amedei, A}, title = {Neurosteroids, Microbiota, and Neuroinflammation: Mechanistic Insights and Therapeutic Perspectives.}, journal = {International journal of molecular sciences}, volume = {26}, number = {14}, pages = {}, pmid = {40725270}, issn = {1422-0067}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Neuroinflammatory Diseases/metabolism/microbiology/therapy ; Animals ; *Neurosteroids/metabolism ; *Neurodegenerative Diseases/metabolism/microbiology ; Brain/metabolism ; Inflammation ; }, abstract = {The gut-brain axis (GBA) represents a complex bidirectional communication network that links the gut microbiota (GM) and the central nervous system (CNS). Recent research has revealed that neurosteroids (NSs) play crucial roles in modulating neuroinflammatory responses and promoting neuroprotection. Meanwhile, GM alterations have been associated with various neuroinflammatory and neurodegenerative conditions, such as multiple sclerosis, Alzheimer's disease, and amyotrophic lateral sclerosis. This review aims to provide a comprehensive overview of the intricate interactions between NS, GM, and neuroinflammation. We discuss how NS and metabolites can influence neuroinflammatory pathways through immune, metabolic, and neuronal mechanisms. Additionally, we explore how GM modulation can impact neurosteroidogenesis, highlighting potential therapeutic strategies that include probiotics, neuroactive metabolites, and targeted interventions. Understanding these interactions may pave the way for innovative treatment approaches for neuroinflammatory and neurodegenerative diseases, promoting a more integrated view of brain health and disease management.}, } @article {pmid40725035, year = {2025}, author = {Bordoni, M and Scarian, E and Viola, C and Dragoni, F and Di Gerlando, R and Rizzo, B and Diamanti, L and Gagliardi, S and Pansarasa, O}, title = {Impact of SOD1 Transcript Variants on Amyotrophic Lateral Sclerosis Severity.}, journal = {International journal of molecular sciences}, volume = {26}, number = {14}, pages = {}, pmid = {40725035}, issn = {1422-0067}, support = {Ricerca Corrente 2022-2024//Italian Ministry of Health/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/pathology ; *Superoxide Dismutase-1/genetics/metabolism ; Middle Aged ; Male ; Female ; Aged ; Severity of Illness Index ; Disease Progression ; Leukocytes, Mononuclear/metabolism ; Cell Line, Tumor ; RNA, Messenger/genetics/metabolism ; Adult ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease that affects motor neurons of people, leading to death. This pathology can be caused by mutations in different genes, including superoxide dismutase 1 (SOD1). Previous studies have pointed out the presence of two transcripts of SOD1, a short one and a long one. The aim of this study was the investigation of these two transcripts both in the SH-SY5Y cell line and in patients' peripheral blood mononuclear cells. We found that the shortest SOD1 transcript is upregulated under stress conditions in both the cellular model and the patients' cells. Moreover, we found a potential correlation between the short SOD1 transcript and the severity of the pathology, which also correlates with the age of patients. No correlation was found between SOD1 transcripts and the progression of the disease. These data suggest a toxic effect of short SOD1 transcripts in ALS patients, by affecting the severity of the pathology making it a possible biomarker for this disease. Interestingly, our data suggest that a short SOD1 transcript does not influence and drive disease progression. The finding of a biomarker will have suitable implications as indicators of disease severity and from the perspective of drug development.}, } @article {pmid40724820, year = {2025}, author = {Tomaszewska-Zaremba, D and Gajewska, A and Misztal, T}, title = {Anti-Inflammatory Effects of Cannabinoids in Therapy of Neurodegenerative Disorders and Inflammatory Diseases of the CNS.}, journal = {International journal of molecular sciences}, volume = {26}, number = {14}, pages = {}, pmid = {40724820}, issn = {1422-0067}, mesh = {Humans ; *Cannabinoids/therapeutic use/pharmacology ; *Neurodegenerative Diseases/drug therapy ; *Anti-Inflammatory Agents/therapeutic use/pharmacology ; Animals ; *Inflammation/drug therapy ; Central Nervous System/drug effects ; *Central Nervous System Diseases/drug therapy ; }, abstract = {Many neurodegenerative diseases are associated with immune system disorders, while neurodegenerative processes often occur in inflammatory conditions of the Central Nervous System (CNS). Cannabinoids exhibit significant therapeutic potential due to their dual ability to modulate both neural and immune functions. These compounds have a broad spectrum of action, allowing them to target multiple pathological mechanisms underlying neurodegenerative and inflammatory CNS diseases. The present review outlines the therapeutic potential of cannabinoids, with a focus on their anti-inflammatory properties, in the treatment of neurodegenerative conditions, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease, as well as inflammatory CNS disorders like multiple sclerosis and HIV-associated dementia.}, } @article {pmid40722336, year = {2025}, author = {Balz, LT and Uttner, I and Weishaupt, J and Ludolph, AC and Taranu, D and Vardakas, I and Jung, S and Fangerau, T and Erhart, DK and Senel, M and Tumani, H and Lulé, DE}, title = {Quality of Life in Multiple Sclerosis Compared to Amyotrophic Lateral Sclerosis: Fatigue and Fast Disease Progression Interferes with the Ability to Psychosocially Adjust.}, journal = {Brain sciences}, volume = {15}, number = {7}, pages = {}, pmid = {40722336}, issn = {2076-3425}, abstract = {Background/Objectives: Multiple sclerosis (MS) is a complex neurological disease that is associated with a broad spectrum of physical and psychological symptoms. Psychosocial adjustment (PSA) refers to the ability to cope with these challenges, which influence quality of life (QoL) and depressiveness in ways not yet fully understood. This study explores the relationship of PSA and disease-specific symptoms in MS, including fatigue, a prominent MS symptom. Additionally, PSA was compared to Amyotrophic Lateral Sclerosis (ALS) to disentangle the impact of disease trajectory on PSA. Methods: We interviewed 77 MS patients using patient-reported outcome measures on QoL and depression and compared them to 30 ALS patients. Confirmatory factor analysis and regression analysis were used to identify PSA indicators and predictors in MS, while t-tests assessed PSA differences across diseases. Results: Key PSA indicators in MS included physical (PQoL), mental (MQoL), and subjective (SQoL) quality of life, as well as depressiveness, with cognitive and motor fatigue emerging as significant predictors. MS patients had higher PQoL and SQoL and lower levels of depression compared to ALS patients, while both groups were comparable with regard to MQoL. Conclusions: PSA in MS is supported by high QoL and low depression levels, with fatigue being a significant predictor. Despite different disease trajectories, patients with MS and ALS showed comparable MQoL, indicating that both diseases similarly impact mental QoL, reflecting a partial overlap in psychosocial adjustment. Overall, psychosocial adjustment was more favorable in MS, likely due to its slower disease progression compared to ALS.}, } @article {pmid40722307, year = {2025}, author = {Ghaderi, S and Mohammadi, S and Fatehi, F}, title = {Magnetic Resonance Neuroimaging in Amyotrophic Lateral Sclerosis: A Comprehensive Umbrella Review of 18 Studies.}, journal = {Brain sciences}, volume = {15}, number = {7}, pages = {}, pmid = {40722307}, issn = {2076-3425}, abstract = {Background/Objectives: Despite extensive research, the underlying causes of amyotrophic lateral sclerosis (ALS) remain unclear. This umbrella review aims to synthesize a vast body of evidence from advanced magnetic resonance imaging (MRI) studies of ALS, encompassing a wide range of neuroimaging techniques and patient cohorts. Methods: Following the PRISMA guidelines, we conducted an extensive search of four databases (PubMed, Scopus, Web of Science, and Embase) for articles published until 3 December 2024. Data extraction and quality assessment were independently performed using the AMSTAR2 tool. Results: This review included 18 studies that incorporated data from over 29,000 ALS patients. Structural MRI consistently showed gray matter atrophy in the motor and extra-motor regions, with significant white matter (WM) atrophy in the corticospinal tract and corpus callosum. Magnetic resonance spectroscopy revealed metabolic disruptions, including reduced N-acetylaspartate and elevated choline levels. Functional MRI studies have demonstrated altered brain activation patterns and functional connectivity, reflecting compensatory mechanisms and neurodegeneration. fMRI also demonstrated disrupted motor network connectivity and alterations in the default mode network. Diffusion MRI highlighted microstructural changes, particularly reduced fractional anisotropy in the WM tracts. Susceptibility-weighted imaging and quantitative susceptibility mapping revealed iron accumulation in the motor cortex and non-motor regions. Perfusion MRI indicated hypoperfusion in regions associated with cognitive impairment. Conclusions: Multiparametric MRI consistently highlights widespread structural, functional, and metabolic changes in ALS, reflecting neurodegeneration and compensatory mechanisms.}, } @article {pmid40722288, year = {2025}, author = {Dhakal, D and Chen, C and Zhang, B and Li, G}, title = {Health-Related Quality of Life, Psychological Health, and Patient-Reported Outcomes of Amyotrophic Lateral Sclerosis Patients in China.}, journal = {Brain sciences}, volume = {15}, number = {7}, pages = {}, pmid = {40722288}, issn = {2076-3425}, abstract = {Objectives: This study explored the health-related quality of life (HRQoL), psychological health, and patient-reported outcomes (PROs) of patients with amyotrophic lateral sclerosis (ALS) in China, providing insights for enhancing clinical care. Methods: A cross-sectional study was conducted among Chinese ALS patients between February and May 2024. Demographics, clinical characteristics, and PROs were assessed. HRQoL and psychological health were evaluated via the 5-item amyotrophic lateral sclerosis assessment questionnaire (ALSAQ-5) and the 4-item patient health questionnaire (PHQ-4), respectively. Spearman's rank correlation, multiple linear regression, and the Kruskal-Wallis H test were used to analyze associations between clinical factors, HRQoL, and psychological health. Results: A total of 237 participants aged 46-65 years (63.3%) were included. The mean ALSAQ-5 score was 64.86±19.34, indicating an impaired HRQoL, whereas the mean PHQ-4 score (5.82 ± 4.10,) suggested varied degree of anxiety and depression. Age, disease duration, ALS severity, fatigue, stress, and pain severity, and respiratory support were significantly associated with HRQoL (p < 0.05). Age, stress severity, and pain severity were significant predictors of psychological distress (p < 0.01). Patients reported diagnostic delay, profound lifestyle changes (96.4%), fear of paralysis (84.8%), and death (49.8%). Most patients (80.6%) expressed a strong desire to stop ALS progression, prioritizing treatments that improve breathing, muscle weakness, swallowing, and mobility issues. Conclusions: ALS profoundly impacts patients' HRQoL and psychological health. Integrating PROs into clinical care strategies is crucial for improving patient outcomes and guiding treatment priorities.}, } @article {pmid40721761, year = {2025}, author = {Xu, H and Zheng, Y and Lu, X and Liu, L and Wan, R and Zhang, S and Li, G and Le, R and Liang, Y}, title = {Accuracy of 7 intraocular lens power calculation formulas in primary angle-closure glaucoma eyes, according to axial length and anterior chamber depth.}, journal = {BMC ophthalmology}, volume = {25}, number = {1}, pages = {431}, pmid = {40721761}, issn = {1471-2415}, support = {(Project Number: MS25H120013)//Zhejiang Provincial Natural Science Foundation Exploration Project./ ; (Project Number: MS25H120013)//Zhejiang Provincial Natural Science Foundation Exploration Project./ ; (Project Number: MS25H120013)//Zhejiang Provincial Natural Science Foundation Exploration Project./ ; (Project Number: MS25H120013)//Zhejiang Provincial Natural Science Foundation Exploration Project./ ; (Project Number: 2025KY1021)//Zhejiang Provincial Medical and Health Project./ ; (Project Number: 2025KY1021)//Zhejiang Provincial Medical and Health Project./ ; (Project Number: 2025KY1021)//Zhejiang Provincial Medical and Health Project./ ; (Project Number: 2025KY1021)//Zhejiang Provincial Medical and Health Project./ ; (Project Number: 2025ZL404)//Zhejiang Province Traditional Chinese Medicine Science and Technology Plan Project/ ; (Project Number: 2025ZL404)//Zhejiang Province Traditional Chinese Medicine Science and Technology Plan Project/ ; (Project Number: 2025ZL404)//Zhejiang Province Traditional Chinese Medicine Science and Technology Plan Project/ ; (Project Number: 2025ZL404)//Zhejiang Province Traditional Chinese Medicine Science and Technology Plan Project/ ; }, mesh = {Humans ; *Glaucoma, Angle-Closure/surgery/physiopathology ; Retrospective Studies ; Female ; *Anterior Chamber/pathology ; Male ; *Lenses, Intraocular ; *Axial Length, Eye/pathology ; Aged ; Middle Aged ; Biometry/methods ; Refraction, Ocular/physiology ; *Optics and Photonics ; Lens Implantation, Intraocular ; Intraocular Pressure/physiology ; Phacoemulsification ; Visual Acuity ; Aged, 80 and over ; Reproducibility of Results ; }, abstract = {PURPOSE: To assess the impact of Axial Length (AL) and anterior chamber depth (ACD) on the performance of the Kane, EVO 2.0, Barrett Universal II (BU II), SRK/T, Haigis, Holladay 2 and Hoffer Q formulas when calculating intraocular lens power in primary angle-closure glaucoma (PACG) patients.

SETTING: Eye hospital, Wen Zhou Medical University, Zhejiang, China.

DESIGN: Retrospective, consecutive case series.

METHODS: Patients who underwent cataract surgery diagnosed with PACG or not were included. The main outcome measures comprised mean prediction error (ME), mean absolute refractive error (MAE), median absolute refractive error (MedAE). Additionally, the proportions of eyes with postoperative refractive errors within ± 0.25 diopter (D), ± 0.50 D, ± 0.75 D, and ± 1.00 D were calculated. Subgroup analyses were conducted based on AL and ACD.

RESULTS: A total of 116 eyes were included, with 66 in the PACG group and 50 in the control group. The PACG group showed significantly larger MAEs compared to the control group. In PACG eyes, the BUII formula tends to cause negative residual refractive errors, while the Kane, EVO, and Holladay 2 formulas often lead to positive ones (P < 0.01). Notably, the SRK/T and Haigis formulas demonstrated better predictability for ME (P < 0.01). PACG patients with an AL under 22 mm or an ACD under 2.5 mm have lower IOL power calculation predictability (P < 0.05). Subgroup analysis shows that PACG eyes with both AL under 22 mm and ACD under 2.5 mm have the lowest predictability and are most prone to significant prediction errors (P < 0.05). A negative correlation was found between postoperative prediction error and AL.

CONCLUSIONS: PACG eyes showed lower prediction accuracy, especially in short ALs and shallow ACD cases. SRK/T and Haigis formulas had better ME predictability. The study stresses optimizing IOL power calculation formulas for PACG eyes, considering AL and ACD effects.}, } @article {pmid40720999, year = {2025}, author = {Zheng, W and Luo, J and Yang, Y and Guo, X and Song, F and Li, F and Xiao, F}, title = {Neural dynamics impairments in amyotrophic lateral sclerosis patients and their associations with clinical characteristics: An observational cohort study.}, journal = {Brain research bulletin}, volume = {229}, number = {}, pages = {111482}, doi = {10.1016/j.brainresbull.2025.111482}, pmid = {40720999}, issn = {1873-2747}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology ; Male ; Middle Aged ; Female ; Electroencephalography/methods ; Aged ; Cohort Studies ; *Brain/physiopathology ; Nonlinear Dynamics ; Adult ; }, abstract = {BACKGROUND AND PURPOSE: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease of the central nervous system. It remains unclear whether pathological changes in ALS can lead to abnormalities in neural dynamics and how these abnormalities relate to key clinical characteristics of ALS.

METHODS: Nonlinear neural dynamics analyses of electroencephalography (EEG) sensorimotor channels were conducted using recurrence quantification analysis (RQA), permutation Lempel-Ziv complexity (PLZC), shannon entropy (ShannonE) and permutation entropy (PermEn). Whole-brain spatiotemporal topological dynamics were assessed using microstate analysis.

RESULTS: The study shows that the nonlinear neural dynamics across all frequency bands in the sensorimotor channels of ALS patients are impaired (reduction in Shannon Entropy of Diagonal Line Length Distribution [ENTR]). Frequency-specific nonlinear neural dynamics indicate increased nonlinear neural dynamics in high-frequency bands (with increases in PLZC in beta2 (20-25 Hz)). Nonlinear neural dynamics in low-frequency bands decreases (with decreases in ShannonE in theta (4-7 Hz)) and is negatively correlated with disease duration. ENTR across all frequency bands and ShannonE in the theta band of the sensorimotor channels are potential protective factors for ALS. Furthermore, sensorimotor channel analysis shows a close relationship with whole-brain spatiotemporal topological neural dynamics. Duration A is positively correlated with RR, DET and ENTR, while Occurrence B is negatively correlated with it.

CONCLUSIONS: The study demonstrates widespread abnormalities in the neural dynamics of ALS, which are closely related to clinical characteristics of ALS. There is also a close relationship between the neural dynamics of sensorimotor channels and whole-brain spatiotemporal topological dynamics in ALS patients.}, } @article {pmid40716120, year = {2025}, author = {Arora, T and Thorgersen, JK and Jones, KE and Allen, SM and Schulze, DG and Dunker, Ø and Tankisi, H and Nilsen, KB}, title = {Test-retest measurement properties of the MScanFit method for motor unit number estimation in individuals with Amyotrophic Lateral Sclerosis.}, journal = {Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology}, volume = {178}, number = {}, pages = {2110940}, doi = {10.1016/j.clinph.2025.2110940}, pmid = {40716120}, issn = {1872-8952}, abstract = {OBJECTIVE: MScanFit is one of the Motor Unit Number Estimation (MUNE) methods considered as a potential biomarker for Amyotrophic Lateral Sclerosis (ALS) diagnosis and clinical trials. We investigated the test-retest measurement properties of MScanFit across multiple muscles in individuals with ALS.

METHODS: We recorded MUNE from Abductor Pollicis Brevis (APB), Abductor Digiti Minimi (ADM), and Tibialis Anterior (TA) muscles in seventeen adults with ALS separated by 1-2 weeks. Intraclass correlation and concordance correlation coefficients provided reliability estimates. Overall agreement was evaluated using pairedt-tests or the Wilcoxon signed-rank test and an estimation statistical approach. The standard error of measurement and the smallest detectable change provided the extent of agreement.

RESULTS: The reliability coefficients ranged from 0.66 to 0.91. The measurement error was high (standard error of measurement > 10 %). The smallest detectable change was high (24-61 units) at an individual level, although smaller (∼10 units) at a group level (N = 10-30) CONCLUSION: MScanFit has moderate-to-excellent reliability and can reliably detect smaller changes at a group level, but is limited in reliably detecting smaller changes at an individual level.

SIGNIFICANCE: The MScanFit MUNE can potentially serve as a group-level biomarker in ALS clinical trials.}, } @article {pmid40716079, year = {2025}, author = {Finsterer, J}, title = {Comment on 'Quantification of Skeletal Muscle at the First Lumbar Level for Prognosis in Amyotrophic Lateral Sclerosis' by Cao et al.}, journal = {Journal of cachexia, sarcopenia and muscle}, volume = {16}, number = {4}, pages = {e70038}, pmid = {40716079}, issn = {2190-6009}, } @article {pmid40720712, year = {2025}, author = {Benatar, M and Cai, X and McDermott, MP and Granit, V and Grignon, AL and Colato, D and Fernandez, MC and Li, Y and McBane, K and Mesa, L and Stanislaw, C and Andersen, PM and Carberry, N and Wuu, J}, title = {Proposed Research Criteria for Mild Motor Impairment as a Prodromal Syndrome in Amyotrophic Lateral Sclerosis.}, journal = {Neurology}, volume = {105}, number = {4}, pages = {e213917}, pmid = {40720712}, issn = {1526-632X}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/diagnosis/physiopathology ; Female ; *Prodromal Symptoms ; Male ; Middle Aged ; Adult ; Longitudinal Studies ; Disease Progression ; Cohort Studies ; Aged ; }, abstract = {BACKGROUND AND OBJECTIVES: The presymptomatic stage of amyotrophic lateral sclerosis (ALS) is typically assumed to be clinically silent. Our previous work, however, has revealed evidence of a prodromal stage, termed mild motor impairment (MMI). In this study, we propose operational criteria for MMI, describe its frequency in a genetically diverse cohort, and examine the association between MMI and time to ALS phenoconversion.

METHODS: Pre-Symptomatic Familial ALS (Pre-fALS) study, initiated in 2007, is a longitudinal natural history and biomarker study of unaffected carriers of any ALS-associated pathogenic variant. Proposed research criteria for MMI were developed based on clinical review of case histories of ALS phenoconverters in the Pre-fALS study. These criteria were then systematically applied to the remaining Pre-fALS cohort. Among phenoconverters and presymptomatic carriers, cumulative probabilities of phenoconversion were estimated for those with and without MMI at baseline. Cox proportional hazard models evaluated associations between risk factors (MMI, age, genotype) and time from baseline to ALS phenoconversion.

RESULTS: The study cohort includes 49 controls (mean age 38.9, 61% female), 153 presymptomatic carriers (mean age 43.1, 61% female), and 31 ALS phenoconverters (mean age 54.4, 58% female). Seven criteria for MMI are proposed, each reflecting a different pattern of upper/lower motor neuron signs, without corresponding weakness, in 1 or more of 4 topographic regions. MMI, defined as meeting ≥1 of these criteria, was observed at 1 or more study visits in 17 of 31 phenoconverters (55%) before clinically manifest ALS, 66 of 153 presymptomatic carriers (43%) who had not yet phenoconverted, and 7 of 49 controls (14%). Among all mutation carriers, the 25th percentile (95% CI) of time to phenoconversion was, respectively, 3.7 (1.6-4.7) and 14.1 (8.9-∞) years for those with and without MMI at baseline, with a hazard ratio of 5.1 (95% CI 2.2-12.2, p < 0.0001). Moreover, the hazard rate of phenoconversion was 1.7 times higher for every 10-year increase in age and varied by genotype.

DISCUSSION: MMI is a recognizable syndrome. Although nonspecific, it identifies presymptomatic carriers at elevated risk of ALS phenoconversion. Combining MMI with emerging biomarkers of underlying pathology may help differentiate those who are prodromal from those who are not prodromal for ALS. Characterization and study of MMI, including replication in other studies, may empower early therapeutic intervention and ALS prevention efforts.}, } @article {pmid40720711, year = {2025}, author = {Hardiman, O}, title = {When Does Amyotrophic Lateral Sclerosis Begin, and How Can We Tell?.}, journal = {Neurology}, volume = {105}, number = {4}, pages = {e214058}, doi = {10.1212/WNL.0000000000214058}, pmid = {40720711}, issn = {1526-632X}, } @article {pmid40717894, year = {2025}, author = {Yu, M and Ma, H and Lai, X and Wu, J and Shen, M and Yan, J}, title = {Stem cell extracellular vesicles: a new dawn for anti-inflammatory treatment of neurodegenerative diseases.}, journal = {Frontiers in aging neuroscience}, volume = {17}, number = {}, pages = {1592578}, pmid = {40717894}, issn = {1663-4365}, abstract = {Mesenchymal stem cell-derived extracellular vesicles, as carriers for intercellular communication, are rich in bioactive substances such as proteins and nucleic acids, and show unique potential in the treatment of neurodegenerative diseases. Their vesicular structure, with a diameter of 30-150 nm, can penetrate the blood-brain barrier and modulate the activity of microglia and astrocytes by delivering functional molecules. This process inhibits the release of pro-inflammatory factors and enhances the expression of anti-inflammatory mediators, thereby alleviating neuroinflammation in the pathological process of neurodegenerative diseases. As natural drug carriers, extracellular vesicles can improve the targeted delivery efficiency of therapeutic molecules. However, their specific anti-inflammatory mechanisms remain not fully understood and require further exploration. This article discusses the anti-inflammatory effects in the context of neurodegenerative diseases and provides a summary and outlook on the anti-inflammatory actions associated with extracellular vesicles from past research.}, } @article {pmid40717876, year = {2025}, author = {Castillo-Bustamante, M and Anderson, C and Gutierrez, VA}, title = {The Use of Posturography in Vestibular Evaluation of Neurodegenerative Disorders: Diagnostic and Rehabilitative Impacts.}, journal = {Cureus}, volume = {17}, number = {7}, pages = {e88752}, pmid = {40717876}, issn = {2168-8184}, abstract = {Neurodegenerative disorders, such as Parkinson's disease, multiple sclerosis, Alzheimer's disease, and amyotrophic lateral sclerosis, frequently present with vestibular dysfunction and balance disturbances, significantly impacting patients' quality of life and increasing the risk of falls. Vestibular impairments in these conditions can manifest as dizziness, unsteadiness, and difficulty maintaining postural control, further complicating the motor and cognitive deficits typical of these diseases. As a result, the assessment and management of balance dysfunction in neurodegenerative disorders have become crucial components of care. Posturography, an objective method for evaluating postural stability and balance control, has emerged as a valuable tool in the vestibular evaluation of patients with neurodegenerative conditions. By providing precise, quantitative measurements of balance deficits, posturography allows for a detailed analysis of postural control mechanisms that may be compromised due to vestibular involvement. This technique not only aids in diagnosing vestibular dysfunction but also plays a key role in developing targeted rehabilitation strategies. When integrated into vestibular rehabilitation (VR) programs, posturography can guide individualized therapy aimed at mitigating fall risk, improving functional mobility, and enhancing patients' overall quality of life. VR exercises, tailored to address specific balance deficits identified through posturographic analysis, can be particularly beneficial in promoting compensatory mechanisms and optimizing patients' functional abilities. This review highlights the significance of posturography as both a diagnostic and therapeutic tool in managing vestibular impairments associated with neurodegenerative diseases, offering the potential for improved outcomes through more personalized and effective rehabilitation interventions.}, } @article {pmid40717814, year = {2025}, author = {Righes, G and Semenzato, L and Koutsikos, K and Zanato, V and Pinton, P and Giorgi, C and Patergnani, S}, title = {The role of autophagy in the pathogenesis and treatment of multiple sclerosis.}, journal = {Autophagy reports}, volume = {4}, number = {1}, pages = {2529196}, pmid = {40717814}, issn = {2769-4127}, abstract = {Autophagy is a crucial cellular process responsible for the degradation and recycling of damaged or unnecessary components, maintaining cellular homeostasis and protecting against stress. Dysregulation of autophagy has been implicated in a variety of neurodegenerative diseases, including multiple sclerosis, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease. Various types of autophagy exist, each with distinct mechanisms, such as macroautophagy, mitophagy, lipophagy, and chaperone-mediated autophagy. These processes are essential for the removal of toxic substrates like protein aggregates and dysfunctional mitochondria, which are vital for neuronal health. In neurodegenerative diseases, the impairment of these clearance mechanisms leads to the accumulation of harmful substances, which accelerate disease progression. Modulating autophagy has emerged as a promising therapeutic strategy, with ongoing studies investigating molecules that can either stimulate or regulate this process. However, despite its potential, significant challenges remain in translating preclinical findings into clinically effective treatments. In this review, we will explore the different types of autophagy, their roles in neurodegenerative diseases, and the therapeutic potential associated with modulating these processes.}, } @article {pmid40717725, year = {2025}, author = {Wen, T and Zhu, J and Sun, S and Chen, Y and Gao, N and Ma, M and Chen, X and Liu, S and Lin, P and Deng, Y}, title = {Thalamic nuclei volumes are related to disease stage in patients with amyotrophic lateral sclerosis.}, journal = {Frontiers in neuroscience}, volume = {19}, number = {}, pages = {1616239}, pmid = {40717725}, issn = {1662-4548}, abstract = {OBJECTIVE: To explore atrophy patterns in thalamic nuclei at different phases of amyotrophic lateral sclerosis (ALS) and determine any correlations between thalamic nucleus volume and either cognitive impairments or motor disabilities.

METHODS: We used the King's clinical staging system for ALS to divide 76 consecutive patients with ALS by disease stage. We investigated patterns of thalamic atrophy in the patients and in 94 healthy controls (HCs). Cognitive functions were evaluated with the Mini-Mental State Examination (MMSE), Frontal Assessment Battery, Boston Naming Test, and Auditory Verbal Learning Test.

RESULTS: Considering all ALS patients, no significant differences were observed in the volume of any thalamic nuclei between the ALS group and HCs. Thalamic nucleus volumes remained normal in ALS patients at King's Stage 2 and Stage 3. However, atrophy was detected in the bilateral anteroventral nucleus, bilateral pulvinar-limitans, bilateral mediodorsal-paratenial-reuniens, bilateral motor hub, bilateral sensory hub, and bilateral intralaminar nucleus in patients who had reached King's Stage 3. In these patients, the volume of the bilateral motor nuclei was associated with the revised ALS Functional Rating Scale scores, and that of the right pulvinar-limitans independently correlated with MMSE scores.

CONCLUSION: Our study provides a comprehensive profile of thalamic atrophy in ALS patients. The thalamic atrophy patterns in these patients extremely differs at different King's Stages, and we suggest that these alterations might result largely from sequential, regional patterns of TDP-43 pathology in ALS. Furthermore, thalamic atrophy might play important roles in motor disability and global cognitive impairments observed in patients with ALS.}, } @article {pmid40715064, year = {2025}, author = {Sinha, IR and Sandal, PS and Spence, H and Burns, GD and Mallika, AP and Abbasinejad, F and Irwin, KE and Cruz, ALF and Wang, V and Marx, SR and Rodríguez, JL and Langmead, B and Gregory, JM and Wong, PC and Ling, JP}, title = {Large-scale RNA-Seq mining reveals ciclopirox olamine induces TDP-43 cryptic exons.}, journal = {Nature communications}, volume = {16}, number = {1}, pages = {6878}, pmid = {40715064}, issn = {2041-1723}, support = {UH3NS115608//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; R33NS115161//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; OAC1920103//National Science Foundation (NSF)/ ; 1U01FD008129//U.S. Department of Health & Human Services | U.S. Food and Drug Administration (U.S. Food & Drug Administration)/ ; R01 NS127186/NS/NINDS NIH HHS/United States ; R33 NS115161/NS/NINDS NIH HHS/United States ; R01NS127186//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; R01NS095969//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; R01 NS095969/NS/NINDS NIH HHS/United States ; P30 AG066507/AG/NIA NIH HHS/United States ; U01 FD008129/FD/FDA HHS/United States ; UH3 NS115608/NS/NINDS NIH HHS/United States ; DGE2139757//National Science Foundation (NSF)/ ; }, mesh = {Humans ; Animals ; Mice ; *Exons/genetics/drug effects ; *Ciclopirox/pharmacology ; *DNA-Binding Proteins/genetics/metabolism ; RNA-Seq ; Amyotrophic Lateral Sclerosis/genetics ; }, abstract = {Nuclear clearance and cytoplasmic aggregation of TDP-43, initially identified in ALS-FTD, are hallmark pathological features observed across a spectrum of neurodegenerative diseases. We previously found that TDP-43 loss-of-function leads to transcriptome-wide inclusion of deleterious cryptic exons, a signature detected in presymptomatic biofluids and postmortem ALS-FTD brain tissue, but the upstream mechanisms that lead to TDP-43 dysregulation remain unclear. Here, we developed a web-based resource (SnapMine) to determine the levels of TDP-43 cryptic exon inclusion across hundreds of thousands of publicly available RNA sequencing datasets. We established cryptic exon inclusion levels across a variety of human cells and tissues to provide ground truth references for future studies on TDP-43 dysregulation. We then explored studies that were entirely unrelated to TDP-43 or neurodegeneration and found that ciclopirox olamine (CPX), an FDA-approved antifungal, can trigger the inclusion of TDP-43-associated cryptic exons in a variety of mouse and human primary cells. CPX induction of cryptic exons arises from heavy metal toxicity and oxidative stress, suggesting that similar vulnerabilities could play a role in neurodegeneration. Our work demonstrates how diverse datasets can be linked through common biological features and underscores how public archives of sequencing data remain a vastly underutilized resource with tremendous potential for uncovering novel insights into complex biological mechanisms and diseases.}, } @article {pmid40713843, year = {2025}, author = {Burg, T and Van Den Bosch, L}, title = {Glycerophospholipids in ALS: insights into disease mechanisms and clinical implication.}, journal = {Molecular neurodegeneration}, volume = {20}, number = {1}, pages = {85}, pmid = {40713843}, issn = {1750-1326}, support = {#00099187//Fondation Thierry Latran/ ; ABMM//ABMM/ ; ALS Liga België (A cure for ALS)//ALS Liga België (A cure for ALS)/ ; 12AIK24N//FWO/ ; G0C1620N//FWO/ ; G088523N//FWO/ ; G026924N//FWO/ ; C14/22/132//Onderzoeksraad, KU Leuven/ ; IDN/22/ 012//Onderzoeksraad, KU Leuven/ ; Muscular Dystrophy Association//Muscular Dystrophy Association/ ; Target ALS//Target ALS/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/metabolism/pathology ; Humans ; *Glycerophospholipids/metabolism ; Animals ; Lipid Metabolism/physiology ; Motor Neurons/metabolism/pathology ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease affecting the adult motor system, with no effective treatments available. Despite extensive research efforts, the exact pathological cascade leading to progressive motor neuron degeneration remains elusive. Recent evidence highlights significant modifications in lipid metabolism during ALS progression, even before the onset of motor symptoms. Glycerophospholipids, the primary components of cellular membranes, are frequently altered in ALS patients and models. These lipids not only play a structural role in membranes, but also contribute to cellular metabolism, signaling pathways, and cell type-specific processes such as neuronal transmission and muscle contraction. In this review, we discuss glycerophospholipid physiological functions in the motor system and review recent studies demonstrating their alterations and the possible underlying pathological mechanisms in ALS. Furthermore, we discuss challenges emerging from studying lipid alterations in neurodegeneration and evaluate the therapeutic potential of glycerophospholipids.}, } @article {pmid40712406, year = {2025}, author = {Sunter, K and Binay, A and Turhan, MA and Koc, MA and Akyol, C and Karahan, ZC and Gecim, IE}, title = {Effect of Preoperative Bowel Preparation and Diet on Anastomotic Healing and the Colon Microbiota: An Experimental Model.}, journal = {The Journal of surgical research}, volume = {313}, number = {}, pages = {516-525}, doi = {10.1016/j.jss.2025.06.061}, pmid = {40712406}, issn = {1095-8673}, abstract = {INTRODUCTION: Intestinal microbiota members, particularly Enterococcus faecalis, play significant roles in the pathogenesis of anastomotic leaks (ALs), with key mechanisms involving collagenase production and matrix metalloproteinase-9 (MMP-9) activation. Diet strongly affects microbiota composition, with Western diets (WDs) promoting dysbiosis, which may exacerbate AL. The effects of mechanical bowel preparation (MBP) and oral antibiotics on AL remain unclear. This experimental study explored the impact of preoperative diet and MBP on AL, focusing on the intestinal microbiota.

METHODS: Sixty-four female Wistar albino rats were fed a WD or standard diet (SD) for 3 weeks before surgery. The rats were subsequently divided into subgroups according to MBP or oral antibiotic administration. Enterococcus colonies were analyzed throughout the procedure, and their correlation with AL was evaluated by assessing collagenase activity and MMP-9 tissue concentrations.

RESULTS: Enterococcus colony collagenase activity was significantly greater in the WD group than in the SD group (P = 0.024). Moreover, anastomotic burst pressures were nonsignificantly lower in the WD group. Finally, MMP-9 levels and collagenase activity were significantly lower in the groups that received either diet with oral antibiotics and MBP than in other subgroups (P = 0.045 and P = 0.007, respectively).

CONCLUSIONS: An SD, especially combined with MBP and oral antibiotics, plays a critical role in reducing the risk of AL by modulating collagenase activity in E faecalis and MMP-9 tissue concentrations in rats. Thus, dietary interventions may improve surgical outcomes; however, further clinical studies are necessary to validate these results in human populations.}, } @article {pmid40710591, year = {2025}, author = {Sadler, GL and Lewis, KN and Narayana, VK and De Souza, DP and Mason, J and McLean, C and Gonsalvez, DG and Turner, BJ and Barton, SK}, title = {Correction: Sadler et al. Lipid Metabolism Is Dysregulated in the Motor Cortex White Matter in Amyotrophic Lateral Sclerosis. Metabolites 2022, 12, 554.}, journal = {Metabolites}, volume = {15}, number = {7}, pages = {}, pmid = {40710591}, issn = {2218-1989}, abstract = {In the original publication [...].}, } @article {pmid40710301, year = {2025}, author = {Pasqualucci, E and Angeletti, D and Rosso, P and Fico, E and Zoccali, F and Tirassa, P and De Virgilio, A and de Vincentiis, M and Severini, C}, title = {Management of Dysarthria in Amyotrophic Lateral Sclerosis.}, journal = {Cells}, volume = {14}, number = {14}, pages = {}, pmid = {40710301}, issn = {2073-4409}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/complications/therapy/physiopathology ; *Dysarthria/therapy/diagnosis/etiology/physiopathology/complications ; Quality of Life ; }, abstract = {Amyotrophic lateral sclerosis (ALS) stands as the leading neurodegenerative disorder affecting the motor system. One of the hallmarks of ALS, especially its bulbar form, is dysarthria, which significantly impairs the quality of life of ALS patients. This review provides a comprehensive overview of the current knowledge on the clinical manifestations, diagnostic differentiation, underlying mechanisms, diagnostic tools, and therapeutic strategies for the treatment of dysarthria in ALS. We update on the most promising digital speech biomarkers of ALS that are critical for early and differential diagnosis. Advances in artificial intelligence and digital speech processing have transformed the analysis of speech patterns, and offer the opportunity to start therapy early to improve vocal function, as speech rate appears to decline significantly before the diagnosis of ALS is confirmed. In addition, we discuss the impact of interventions that can improve vocal function and quality of life for patients, such as compensatory speech techniques, surgical options, improving lung function and respiratory muscle strength, and percutaneous dilated tracheostomy, possibly with adjunctive therapies to treat respiratory insufficiency, and finally assistive devices for alternative communication.}, } @article {pmid40709577, year = {2025}, author = {Dukic, S and van Veenhuijzen, K and Westeneng, HJ and McMackin, R and van Eijk, RPA and Sleutjes, BTHM and Nasseroleslami, B and Hardiman, O and van den Berg, LH}, title = {Altered EEG Response of the Parietal Network in Asymptomatic C9orf72 Carriers.}, journal = {Human brain mapping}, volume = {46}, number = {11}, pages = {e70275}, pmid = {40709577}, issn = {1097-0193}, support = {AV2022-0004//Stichting ALS Nederland/ ; AV2022-0005//Stichting ALS Nederland/ ; 23-PPG-674-1//The ALS Association/ALS Finding A Cure/ ; }, mesh = {Humans ; Male ; Female ; *C9orf72 Protein/genetics ; Electroencephalography ; Middle Aged ; Adult ; *Amyotrophic Lateral Sclerosis/physiopathology/genetics ; *Parietal Lobe/physiopathology ; Aged ; Heterozygote ; *Nerve Net/physiopathology ; Reaction Time/physiology ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by motor neuron degeneration. Around 10% of cases have a genetic basis, with the C9orf72 hexanucleotide repeat expansion being the most common cause in individuals of European ancestry. Detecting early alterations in at-risk individuals could aid in identifying biomarkers for timely diagnosis and intervention. In this study, we investigated electrophysiological changes in asymptomatic C9orf72 mutation carriers using EEG, focusing on cognitive and motor networks, as these individuals are at risk of developing impairments in both domains. This study included 87 asymptomatic family members (AFM) of patients with familial C9orf72 ALS, comprising 37 individuals carrying the pathological repeat expansion (C9+) and 50 without it (C9-). High-density EEG was recorded during the sustained attention to response task (SART), which is a Go/NoGo paradigm that engages the frontoparietal and motor networks. Task performance was recorded and six behavioral measures were extracted: NoGo accuracy, Go accuracy, total accuracy, anticipation error, average response time, and response time variability. Analyses were conducted on EEG data in both sensor- and source-space, using stimulus- and response-locked data. The stimulus-locked Go and NoGo data were analysed within two time windows: 180-350 ms (N2) and 300-600 ms (P3), while response-locked Go data were analysed within a -100 to 100 ms time window. Linear mixed models were used to quantify differences between groups, incorporating familial pedigree to control for between-subject dependencies. While the two groups did not significantly differ in any SART performance measures, EEG analyses revealed differences. During the stimulus-locked N2, significant differences were observed in sensor-space, primarily in central electrodes during both NoGo and Go conditions, with C9+ AFM exhibiting an increased negative potential. Source analysis confirmed these findings and localized the increased activity in the bilateral precuneus and superior parietal regions. Further analysis of the response-locked data supported the involvement of the same posterior regions. No significant relationships were found between these EEG observations and SART performance. These findings provide the first evidence of EEG changes in AFM carrying the C9orf72 repeat expansion. The observed functional changes in the parietal regions may reflect genotype-related effects on the motor control network, potentially contributing to early pathophysiology. In contrast, clinical assessments and task performance did not differ between groups, suggesting that our EEG findings may hold promise as biomarkers for monitoring the risk of conversion to symptomatic disease and warrant further exploration to assess their predictive value for future symptom onset.}, } @article {pmid40709254, year = {2025}, author = {Dokholyan, N and Hnath, B and Dokholyan, R and Simmons, Z}, title = {Trimeric superoxide dismutase 1 antibody as a universal biomarker for ALS.}, journal = {Research square}, volume = {}, number = {}, pages = {}, pmid = {40709254}, issn = {2693-5015}, support = {R35 GM134864/GM/NIGMS NIH HHS/United States ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that leads to the loss of motor neurons, resulting in paralysis and death. Currently, there are no specific biomarkers available for diagnosing ALS. As a result, diagnosis currently relies on excluding other conditions, which forces patients to endure months or even years of uncertainty. The absence of a specific, reliable diagnostic tool has hindered both early intervention and therapeutic progress. Here we develop a novel synthetic antibody that can detect a toxic form of a known protein linked to ALS. This trimeric assembly of superoxide dismutase 1 (SOD1) is a soluble, structurally distinct oligomer that is highly toxic in cell models. The antibody selectively binds this trimer and differentiates individuals with the disease from healthy people and from those with other neurodegenerative diseases (Alzheimer's and Parkinson's disease). This breakthrough provides the first disease-specific diagnostic tool for this condition and reveals a shared pathological signature across patients, even in cases without genetic mutations. After decades without a specific diagnostic tool, this antibody signifies a long-awaited breakthrough, finally offering clinicians and researchers a reliable window into ALS pathology.}, } @article {pmid40709087, year = {2025}, author = {Wang, G and Zhou, X and Pang, X and Ma, K and Li, L and Song, Y and Hou, D and Wang, X}, title = {Pharmacological effects, molecular mechanisms and strategies to improve bioavailability of curcumin in the treatment of neurodegenerative diseases.}, journal = {Frontiers in pharmacology}, volume = {16}, number = {}, pages = {1625821}, pmid = {40709087}, issn = {1663-9812}, abstract = {With the global population aging, the incidence of neurodegenerative diseases (NDs), such as Alzheimer's disease, Parkinson's disease, Huntington's disease and amyotrophic lateral sclerosis, has been progressively increasing. However, effective therapeutic strategies and clinical drugs for these disorders remain scarce. Curcumin, a natural polyphenolic compound primarily derived from the herbaceous plant Curcuma longa L., has been proposed as a promising candidate for ND treatment based on the excellent antioxidant, anti-inflammatory and neuroprotective properties. Its pharmacological activities encompass scavenging reactive oxygen species, mitigating toxic protein aggregation and cytotoxicity, repairing mitochondrial dysfunction, and inhibiting excessive neuronal apoptosis. Compared with synthetic drugs, curcumin demonstrates a more favorable safety profile with fewer side effects. Nevertheless, its clinical application is substantially hindered by poor bioavailability, which stems from low aqueous solubility, inefficient intestinal absorption, and rapid metabolism and systemic elimination. Conventional administration methods often fail to achieve effective concentrations in vivo. Further clinical trials are also required to validate the therapeutic efficacy and potential adverse effects in human subjects. This article systematically reviews the pathogenesis of NDs and the knowledge on curcumin including pharmacological effects, neuroprotective mechanisms, functions across specific NDs and advanced strategies to enhance the bioavailability, with the aim of promoting the development and clinical translation of curcumin-based therapeutics for NDs.}, } @article {pmid40708508, year = {2025}, author = {Rana, A and Malviya, R and Rajput, S and Sridhar, SB and Wadhwa, T}, title = {Trends in Nanoparticle-based Strategies for the Management of Neuroinflammation.}, journal = {CNS & neurological disorders drug targets}, volume = {}, number = {}, pages = {}, doi = {10.2174/0118715273373041250707012835}, pmid = {40708508}, issn = {1996-3181}, abstract = {Neuroinflammation, characterised by an overactive immune system in the brain and spinal cord, has now been tied to several neurodegenerative diseases. Here, immune cells invade into the brain, activating astrocytes and microglia. Neuroinflammation is a common symptom of many neurodegenerative illnesses, including Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). This inflammatory reaction occurs within the central nervous system (CNS). Neurological dysfunction results from the inflammatory response, which arises in reaction to any kind of brain injury. Regulating neuroinflammation can be useful for controlling brain disorders associated with neuroinflammation. Several targeted drug delivery systems attempt to treat neuroinflammation caused by neurodegenerative illnesses or brain tumours by targeting the microglia and other immune cells in the central nervous system. Therefore, biodegradable and biocompatible NPs (nanoparticles) could be developed as a treatment for neurodegenerative diseases caused by neuroinflammation or as a less invasive means of transporting other drugs across the blood-brain barrier. Numerous applications of gold nanoparticles (AuNPs) in the treatment of neurological diseases, including Alzheimer's disease (AD) and Parkinson's disease (PD), are studied in this article. To prevent neuroinflammation and microglia over-activation, some NPs have recently been found to be effective anti-inflammatory medication carriers that cross the blood-brain barrier.}, } @article {pmid40707812, year = {2025}, author = {Akbari Lakeh, M and Bootsma, S and van Nellestijn, R and Tinnevelt, GH and Jansen, JJ}, title = {An end-to-end data analysis framework for real-time detection and source identification of pollution events via e-nose networks.}, journal = {Analytical and bioanalytical chemistry}, volume = {}, number = {}, pages = {}, pmid = {40707812}, issn = {1618-2650}, support = {TKITOETKI2020_EBI//TKI E&I/ ; }, abstract = {Ambient air pollution contributes to an estimated 4.2 million premature deaths worldwide each year, underscoring the imperative for advanced air quality management tools. In heavily industrialized regions, diffuse fugitive leaks and concentrated stack emissions threaten public health and ecosystems, making real-time monitoring and accurate source apportionment indispensable. To address these challenges, we introduce an end-to-end data analysis framework that employs a distributed network of low-cost electronic noses (e-noses) to deliver spatially and temporally resolved emission monitoring. The real-time, high-resolution outputs of e-noses are deconvoluted into discrete emission events using a chemometric pipeline including principal component analysis (PCA), hierarchical cluster analysis (HCA), and multivariate curve resolution-alternating least squares (MCR-ALS). Each event is then characterized within a 5W attribution schema, which identifies what anomaly was detected, when, and where it occurred, why it arose, and who is responsible for mitigation, thereby creating a searchable database of pollution incidents. By combining real-time, low-cost sensing with robust multivariate analysis and stakeholder-centered reporting, this framework enables transparent emission accountability. In turn, it supports rapid mitigation responses and strengthens regulatory compliance in complex industrial regions.}, } @article {pmid40707625, year = {2025}, author = {Watanabe, Y and Suzuki, N and Nakagawa, T and Hosogane, M and Akiyama, T and Kageyama, N and Funayama, Y and Warita, H and Morimoto, S and Okano, H and Aoki, M and Nakayama, K}, title = {ALS-associated RNA-binding proteins promote UNC13A transcription through REST downregulation.}, journal = {The EMBO journal}, volume = {}, number = {}, pages = {}, pmid = {40707625}, issn = {1460-2075}, support = {22K15702//MEXT | Japan Society for the Promotion of Science (JSPS)/ ; 21K07411//MEXT | Japan Society for the Promotion of Science (JSPS)/ ; 23H02821//MEXT | Japan Society for the Promotion of Science (JSPS)/ ; 21H02458//MEXT | Japan Society for the Promotion of Science (JSPS)/ ; 24K02300//MEXT | Japan Society for the Promotion of Science (JSPS)/ ; JP21H05278//MEXT | Japan Society for the Promotion of Science (JSPS)/ ; JP22K15736//MEXT | Japan Society for the Promotion of Science (JSPS)/ ; JP23bm1123046//Japan Agency for Medical Research and Development (AMED)/ ; JP23kk0305024//Japan Agency for Medical Research and Development (AMED)/ ; JP21wm0425009//Japan Agency for Medical Research and Development (AMED)/ ; JP23bm1423002//Japan Agency for Medical Research and Development (AMED)/ ; JP24ek0109631//Japan Agency for Medical Research and Development (AMED)/ ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by selective loss of motor neurons. Although multiple pathophysiological mechanisms have been identified, no comprehensive understanding of these heterogeneous processes has been achieved. The ALS-associated RNA-binding protein (RBP) TDP-43 has previously been shown to stabilize UNC13A mRNA by preventing cryptic exon inclusion. Here, we show that the ALS-associated RBPs MATR3, FUS, and hnRNPA1 regulate UNC13A expression by targeting the transcriptional repressor REST. These RBPs bind to and downregulate REST mRNA to promote UNC13A transcription. Loss of any of these RBPs in cultured cells or in iPSC-derived motor neurons carrying the ALS-causing FUS P525L mutation leads to REST overexpression, and the same is observed in motor neurons of individuals with familial or sporadic ALS. The functional convergence of four RBPs on the regulation of UNC13A expression underscores the important role of this process for synaptic integrity, and its association with ALS pathogenesis could be relevant for the development of new therapeutic agents.}, } @article {pmid40707187, year = {2025}, author = {Kikuchi, R and Ishihara, K and Shiota, J and Kawamura, M and Yoshida, M}, title = {[An autopsy case of spinal bulbar muscular atrophy concomitant with multiple system atrophy pathology].}, journal = {Rinsho shinkeigaku = Clinical neurology}, volume = {}, number = {}, pages = {}, doi = {10.5692/clinicalneurol.cn-002087}, pmid = {40707187}, issn = {1882-0654}, abstract = {We describe an autopsy case of spinal bulbar muscular atrophy (SBMA) concomitant with multiple system atrophy (MSA). A Japanese male patient developed gait disturbance in his twenties. His brother and niece also presented with similar clinical symptoms. His condition gradually worsened, and he became immobile at the age of 50 years. Genetic analysis revealed the expansion of CAG repeats of the SBMA gene. At 63 years of age, cerebellar ataxia symptoms emerged. Magnetic resonance images of the head showed a "hot cross bun sign" at the pontine basis and bilateral atrophy of the middle cerebellar peduncles and cerebellar hemispheres, suggesting MSA. He died of pneumonia at the age of 65 years, with a clinical illness of approximately 40 years. The neuropathological diagnosis was consistent with both SBMA and MSA. Neurons of the spinal anterior horn and brainstem motor nuclei were diminished. 1C2 (polyglutamine) immunoreactive intranuclear and intracytoplasmic inclusions were observed in the neurons in the substantia nigra, brainstem tegmentum, pontine nuclei, spinal anterior horn cells and Onuf's nucleus. These findings were suggestive of SBMA. Meanwhile, neurons of the inferior olivary nuclei, pontine nuclei, and Purkinje cells were nearly completely lost. The cerebellar white matter, pontine basis, and middle cerebellar peduncles showed a prominent loss of fibers. α-synuclein positive glial cytoplasmic inclusions were observed in widespread areas. These findings were suggestive of MSA. To the best of our knowledge, another case of SBMA accompanying MSA, similar to the present case, have been reported to date. Moreover, several cases of pathologically proven amyotrophic lateral sclerosis and MSA have been reported. The development of molecular biological techniques and accumulation of pathologically diagnosed patients may reveal common pathological mechanisms in SBMA and MSA.}, } @article {pmid40706981, year = {2025}, author = {Saenz-Martinez, E and Collia, M and Rodriguez-Garraus, A and Gil, AG and López de Cerain, A and Azqueta, A}, title = {Evaluation of Potassium Bromate as a Positive Control in the In Vivo Fpg-Modified Comet Assay for the Detection of Oxidized Bases.}, journal = {Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association}, volume = {}, number = {}, pages = {115663}, doi = {10.1016/j.fct.2025.115663}, pmid = {40706981}, issn = {1873-6351}, abstract = {The in vivo comet assay is validated for genotoxicity testing and included in ICH, ECHA, and EFSA strategies. However, OECD test guideline (TG) 489 In vivo Mammalian Alkaline Comet Assay covers only the standard version, detecting DNA strand breaks (SB) and alkali-labile sites (ALS), limiting mechanistic insights. Inclusion of the enzyme formamidopyrimidine DNA glycosylase (Fpg) allows detection of oxidised bases; 52 studies using enzymes to reveal DNA lesions undetectable with the standard comet assay were identified (Collins et al. 2020). Despite its frequent use, fewer than one-third of studies employing enzymes include positive controls, which would aid standardization and OECD TG 489 integration. The present study evaluates potassium bromate (KBrO3) as a potential positive control for the Fpg-modified comet assay. Wistar rats were dosed twice by oral gavage with different doses of KBrO3 following OECD TG 489 principles, with DNA damage assessed in liver, duodenum, kidney, brain, and whole blood. Ethyl methanesulfonate (EMS) was used as a positive control for the standard version. The inclusion of Fpg digestion enhances assay sensitivity and specificity, and DNA oxidation damage induced by KBrO3 is detected in kidney, liver, and duodenum within 3 hours indicating that it may be a good positive control.}, } @article {pmid40706681, year = {2025}, author = {Murat de Montai, Q and Perray, L and Mathian, A and Dorgham, K and Gorochov, G and Charre, C and Chasset, F}, title = {Invited Reply to Chen et al's ''Response to Quitterie Murat de Montai et al, 'Interferon-α biological activity is associated with disease activity and risk of flare in cutaneous lupus erythematosus: A monocentric study of 184 patients'".}, journal = {Journal of the American Academy of Dermatology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jaad.2025.07.041}, pmid = {40706681}, issn = {1097-6787}, } @article {pmid40706449, year = {2025}, author = {Sluyts, Y and Van Schil, K and Deconinck, T and Oedit, R and Baets, J and De Ridder, W}, title = {TBK1-associated motor neuron disease with concomitant vacuolar myopathy: a case resembling a multisystem proteinopathy.}, journal = {Neuromuscular disorders : NMD}, volume = {53}, number = {}, pages = {105445}, doi = {10.1016/j.nmd.2025.105445}, pmid = {40706449}, issn = {1873-2364}, abstract = {We present a 75-year-old patient with an amyotrophic lateral sclerosis (ALS)-myopathy overlap phenotype and a pathogenic variant in TBK1. The ALS-myopathy overlap phenotype was extensively documented clinically, with mixed myopathic and neurogenic findings on needle EMG, muscle MRI and muscle biopsies, with presence of rimmed vacuoles immunoreactive for P62 in particular. A concomitant presentation of motor neuron disease (MND) and myopathy is most notably associated with a very rare, inherited group of diseases, known as multisystem proteinopathies (MSPs). An increasing number of genes have already been linked to an MSP phenotype, of which VCP-related MSP is the most frequent. In this report we expand the spectrum of clinical presentations of TBK1-associated disease and describe pathophysiological similarities between TBK1- and VCP-related disease.}, } @article {pmid40705135, year = {2025}, author = {Jung, HJ and Jeong, WS and Kang, HW and Kang, M and Lee, EJ and Lim, YM and Park, JS and Kim, H}, title = {Serum GFAP predicts survival in advanced ALS: a prospective multicenter study.}, journal = {Journal of neurology}, volume = {272}, number = {8}, pages = {532}, pmid = {40705135}, issn = {1432-1459}, support = {RS-2023-00211443//Ministry of Science and ICT, Republic of Korea/ ; 2023IP0108//Asan Institute for Life Science, Asan Medical Center, Seoul, Republic of Korea/ ; 25-BR-04-01//KBRI basic research program through Korea Brain Research Institute funded by Ministry of Science and ICT, Republic of Korea/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/blood/mortality/diagnosis ; *Glial Fibrillary Acidic Protein/blood ; Male ; Female ; Middle Aged ; *Neurofilament Proteins/blood ; Aged ; *Brain-Derived Neurotrophic Factor/blood ; Biomarkers/blood ; Prospective Studies ; Disease Progression ; Adult ; Prognosis ; ROC Curve ; }, abstract = {BACKGROUND: Neurofilament light chain (NfL) is a well-established biomarker of axonal damage in amyotrophic lateral sclerosis (ALS), but its limited disease specificity warrants the identification of complementary markers. This study aimed to evaluate the prognostic value of serum glial fibrillary acidic protein (GFAP) and brain-derived neurotrophic factor (BDNF) as adjunctive biomarkers to NfL in ALS.

METHODS: Serum NfL, GFAP, and BDNF levels were measured using ultrasensitive single-molecule array (SIMOA) assays in two independent ALS cohorts from Asan Medical Center (n = 65) and Kyungpook National University Chilgok Hospital (n = 53), along with 15 healthy controls. Diagnostic performance was evaluated using receiver operating characteristic (ROC) curve analysis. Associations with clinical severity, disease progression rate, and survival were evaluated using correlation analyses, Kaplan-Meier survival estimates, and Cox proportional hazards models.

RESULTS: Serum NfL, GFAP, and BDNF levels were significantly elevated in ALS versus controls, with area under the curve (AUC) values of 0.969, 0.613, and 0.875, for NfL, GFAP, and BDNF, respectively. NfL and GFAP levels increased with advancing King's stage (NfL: τ = 0.226, p = 0.011; GFAP: τ = 0.160, p = 0.023), though only NfL correlated with disease progression rate (r = 0.309, p = 0.001). Notably, elevated GFAP was independently associated with poorer survival in advanced ALS (King's stage 3-4), with a hazard ratio of 6.907 (95% CI: 1.978-24.119, p = 0.002).

CONCLUSIONS: While NfL remains a robust marker of ALS progression, GFAP may serve as an independent prognostic marker in late-stage disease. Combining these markers may enhance prognostic accuracy and support personalized ALS care.

Neurofilament light chain (NfL) is a widely accepted biomarker for axonal damage in ALS and correlates with disease progression. However, its lack of disease specificity limits its standalone prognostic value, necessitating the discovery of complementary biomarkers to improve prognostic accuracy.

WHAT THIS STUDY ADDS: This study demonstrates that while NfL remains a strong indicator of ALS progression, glial fibrillary acidic protein (GFAP) serves as an independent prognostic marker, particularly in advanced stages of the disease. Furthermore, it shows that serum BDNF levels are also elevated in ALS patients.

Combining NfL and GFAP as a biomarker panel could significantly enhance prognostic accuracy and facilitate more personalized treatment strategies for ALS patients, especially in later disease stages. This could guide clinical trial design and improve patient stratification for therapeutic interventions.}, } @article {pmid40704991, year = {2025}, author = {Ganssauge, J and Hawkins, S and Namboori, SC and Leung, SK and Mill, J and Bhinge, A}, title = {Rapid and inducible mislocalization of endogenous TDP43 in a novel human model of amyotrophic lateral sclerosis.}, journal = {eLife}, volume = {13}, number = {}, pages = {}, pmid = {40704991}, issn = {2050-084X}, mesh = {Humans ; *DNA-Binding Proteins/metabolism/genetics ; *Amyotrophic Lateral Sclerosis/pathology/metabolism/genetics ; Induced Pluripotent Stem Cells/metabolism ; Neurons/metabolism/pathology ; Cytoplasm/metabolism ; Cell Nucleus/metabolism ; Protein Transport ; }, abstract = {Transactive response DNA binding protein 43 kDa (TDP43) proteinopathy, characterized by the mislocalization and aggregation of TDP43, is a hallmark of several neurodegenerative diseases, including Amyotrophic Lateral Sclerosis (ALS). In this study, we describe the development of a new model of TDP43 proteinopathy using human induced pluripotent stem cell (iPSC)-derived neurons. Utilizing a genome engineering approach, we induced the mislocalization of endogenous TDP43 from the nucleus to the cytoplasm without mutating the TDP43 gene or using chemical stressors. Our model successfully recapitulates key early and late pathological features of TDP43 proteinopathy, including neuronal loss, reduced neurite complexity, and cytoplasmic accumulation and aggregation of TDP43. Concurrently, the loss of nuclear TDP43 leads to splicing defects, while its cytoplasmic gain adversely affects microRNA expression. Strikingly, our observations suggest that TDP43 is capable of sustaining its own mislocalization, thereby perpetuating and further aggravating the proteinopathy. This innovative model provides a valuable tool for the in-depth investigation of the consequences of TDP43 proteinopathy. It offers a clinically relevant platform that will accelerate the identification of potential therapeutic targets for the treatment of TDP43-associated neurodegenerative diseases, including sporadic ALS.}, } @article {pmid40704719, year = {2025}, author = {Rafiei, F and Jadidi, K and Nejat, F and Khabazkhoob, M and Nabovati, P}, title = {Ophthalmic Quality of Life and Its Association With Visual Function, Accommodative and Binocular Vision Performance in Keratoconus Patients: A Study Using Rasch Analysis‏.}, journal = {Cornea}, volume = {}, number = {}, pages = {}, doi = {10.1097/ICO.0000000000003935}, pmid = {40704719}, issn = {1536-4798}, abstract = {PURPOSE: To investigate the relationship between ophthalmic quality of life with visual function and accommodative/binocular vision performance in patients with keratoconus (KCN), using the Keratoconus Outcomes Research Questionnaire (KORQ).

METHODS: Seventy patients with KCN were recruited in this study (average age: 27.04 ± 5.60). A Persian adaptation of the KORQ was developed, and its psychometric properties were evaluated through Rasch analysis. The associations between study variables and the KORQ subscales, activity limitations (AL-S) and symptoms (S-S), were evaluated through linear regression models.

RESULTS: The Persian KORQ demonstrated good psychometric properties after removing items 5 and 8 from the AL-S and items 4 and 5 from the S-S. The analysis showed a statistically significant direct association between the AL-S score and age (β: 0.280, P < 0.05). In addition, there was a statistically significant direct relationship between the AL-S score with best-corrected visual acuity in the better eye (β: 0.279, P = 0.048), binocular contrast sensitivity (β: 0.319, P = 0.033), and steep keratometry in the better eye (β: 0.409, p-0.007). The near negative fusional vergence parameters-blur (β: -0.460, P = 0.012), break (β: -0.403, P = 0.027), and recovery (β: -0.391, P = 0.033)-showed a statistically significant inverse association with the S-S score.

CONCLUSIONS: The Persian KORQ is a reliable tool for assessing ophthalmic quality of life in Persian-speaking patients with KCN. The KCN-related AL-S are primarily influenced by age, basic visual functions, and the severity of KCN in the better eye. Deficits in certain binocular vision metrics, particularly a diminished near negative fusional vergence amplitude, may contribute to the symptoms reported by patients with KCN.}, } @article {pmid40704616, year = {2025}, author = {Young, CA and Chaouch, A and Mcdermott, CJ and Al-Chalabi, A and Chhetri, SK and Bidder, C and Ellis, C and Annadale, J and Mills, RJ and Tennant, A and , }, title = {Fatigue in amyotrophic lateral sclerosis/motor neuron disease: prevalence, influences and trajectories.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {}, number = {}, pages = {1-12}, doi = {10.1080/21678421.2025.2533881}, pmid = {40704616}, issn = {2167-9223}, abstract = {Objective: In a large cohort of people with amyotrophic lateral sclerosis/motor neuron disease (pwALS), we examined the age-sex prevalence of fatigue, its relationship to other symptoms and functioning, and trajectories over time. Methods: Data from the Trajectories of Outcome in Neurological Conditions study were analyzed by Rasch analysis, structural equation and group-based trajectory models. Results: Fatigue was reported by 97.8% on Neurological Fatigue Index-MND (NFI-MND) and 96.4% on Numeric Rating Scale Fatigue among 1058 pwALS: mean age 65 (range 20-90); mean duration 23 months (range 0-301); 60.7% male; onset 26.5% Bulbar, 71.5% Limb and 2.0% Respiratory. Mean (metric) level on NFI-MND was 12.8 (SD 5.3; range 0-24). Cut-points on the NFI-MND of 10 and 15 divided fatigue into mild (27.3%); moderate (36.1%) and severe (36.2%). Structural equation modeling showed that function, cognition, spasticity, dyspnea and pain have descending order of effect. Over average 11.6 months follow-up, 60.5% had stable fatigue, 23.8% increased fatigue level, while 15.8% showed declining fatigue. Trajectory analysis showed three groups, low, average and high fatigue. Those with low trajectories had less spasticity, worry, cognitive problems, as well as better functioning, longer duration and were less likely to be male. High fatigue trajectory was associated with worse spasticity, cognition and anxiety. Conclusions: Fatigue is extremely common among pwALS, thus more work is required on fatigue management. In addition to treating fatigue itself, the current study shows that targeting cognition, spasticity, dyspnea and pain might be fruitful.}, } @article {pmid40703981, year = {2025}, author = {Yang, C and Feng, T and Hu, F}, title = {Progranulin deficiency does not exacerbate TDP-43 pathology in TDP-43 transgenic mouse models.}, journal = {NPJ dementia}, volume = {1}, number = {1}, pages = {16}, pmid = {40703981}, issn = {3005-1940}, abstract = {The progranulin (PGRN) protein is tightly linked with TDP-43 proteinopathy in neurodegenerative diseases. However, how PGRN regulates TDP-43 proteinopathy remains unclear. In this study, we investigated the effect of PGRN loss on TDP-43 pathology in the TDP-43[Q331K] knock-in mice expressing an ALS-linked TDP-43 mutation at the endogenous level, and in the transgenic mice overexpressing human TDP-43 in neurons. We found that PGRN deficiency leads to mild glial activation and behavioral deficits in TDP-43[Q331K] mice without inducing typical TDP-43 pathology. RNA-seq analysis reveals upregulation of immune pathways and downregulation of myelination-related pathways in PGRN-deficient TDP-43[Q331K] mice. In addition, we observed myelination defects in human TDP-43 transgenic mice, but PGRN loss does not exacerbate TDP-43 pathology, myelination defects, and motor deficits in this mouse strain. Our studies demonstrated that PGRN deficiency exacerbates behavioral deficits and glial pathology caused by TDP-43 Q331K mutation but has minimal effect on TDP-43 pathology in mouse models.}, } @article {pmid40703193, year = {2025}, author = {Govaarts, R and Scheijbeler, EP and Beeldman, E and Fraschini, M and Griffa, A and Engels, MMA and van der Kooi, AJ and Pijnenburg, YAL and de Visser, M and Stam, CJ and Raaphorst, J and Hillebrand, A}, title = {Longitudinal changes in MEG-based brain network topology of ALS patients with cognitive/behavioral impairment-An exploratory study.}, journal = {Network neuroscience (Cambridge, Mass.)}, volume = {9}, number = {3}, pages = {824-841}, pmid = {40703193}, issn = {2472-1751}, abstract = {Amyotrophic lateral sclerosis (ALS) with only motor impairment (ALS-pure motor) and the behavioral variant of frontotemporal dementia (bvFTD) are hypothesized to represent extreme ends of a disease spectrum, which encompasses ALS with cognitive/behavioral impairment (ALSci/bi). In this longitudinal magnetoencephalography (MEG) study, we investigated changes in brain network topology of ALSci/bi over time as compared with ALS-pure motor and bvFTD patients. Resting-state MEG was recorded in ALS-pure motor (n = 9), ALSci/bi (n = 16), and bvFTD (n = 16) at baseline and 5-month follow-up, projected to source space. The corrected version of the amplitude envelope correlation was applied to compute frequency-band-specific functional connectivity between brain regions, from which the backbone of the functional networks was constructed using the minimum spanning tree (MST) approach. Reference MSTs were computed based on the functional connectivity matrices for ALS-pure motor and bvFTD, against which the networks of ALSci/bi were compared. We showed that, at baseline, networks in the theta band of ALSci/bi patients were more similar to ALS-pure motor than bvFTD. At follow-up, ALSci/bi patients' beta-band network similarity had moved away from ALS-pure motor and resembled bvFTD. In conclusion, our findings suggest that brain networks of ALSci/bi patients move along the ALS-bvFTD spectrum over time, from ALS-pure motor to bvFTD-like topology.}, } @article {pmid40702789, year = {2025}, author = {Zota, I and Calogeropoulou, T and Chanoumidou, K and Charalampopoulos, I and Gravanis, A}, title = {Synthetic microneurotrophins: Neurotrophin receptors for therapeutics of neurodegenerative diseases.}, journal = {British journal of pharmacology}, volume = {}, number = {}, pages = {}, doi = {10.1111/bph.70143}, pmid = {40702789}, issn = {1476-5381}, support = {Dinnesmin//FP7 Health/ ; //European Regional Development Fund of the European Union and Greek/ ; }, abstract = {Neurodegenerative disorders are characterised by the chronic progressive degeneration of specific neuronal subtypes, neuroinflammation, myelin damage and synaptic loss. Despite their growing incidence, advancements in effective treatments remain limited, because of lack of knowledge for the aetiology of the diverse pathophysiology to design systematic therapies. Several studies highlight the role of neurotrophic factors (NTFs) as potential neuroprotective, regenerative therapies for these disorders. Although NTFs hold protective and regenerative potential for chronic neuroinflammatory and neurodegenerative conditions, major hurdles impair their clinical use, such as optimising the dosage of NTFs, minimising the invasiveness of delivery methods, overcoming blood-brain-barrier (BBB) impermeability and managing side effects. In the last two decades our group have synthesised and screened a large chemical library of steroidal analogues of dehydroepiandrosterone (DHEA), an endogenous steroid hormone, for their ability to mimic neurotrophin neuroprotective and neurogenic actions. Interestingly, DHEA was shown to interact with all neurotrophin receptors, acting most probably as an ancestral neurotrophin early in evolution. However, its chronic pharmacological use is questioned by its action as a major precursor of steroidogenesis. This review highlights the findings of numerous preclinical studies on these synthetic, non-toxic, BBB permeable DHEA derivatives, named microneurotrophins (MNTs), deprived of endocrine actions, activators of specific neurotrophin receptors. The multimodal actions of MNTs against neuronal death and activation of microglia, in addition to their beneficial effects in synaptogenesis and neurogenesis, place them as interesting lead molecules in the armamentarium of therapeutics for neurodegeneration.}, } @article {pmid40702249, year = {2025}, author = {Sulthana, N and Mittal, P and Goyal, A and Ballal, S and Maharana, L and Rana, AJ and Khan, Y and Goyal, K and Mishra, R and Ali, H and Gupta, G and Hussain, MS}, title = {Targeting ASK1 signaling in neurodegeneration: molecular insights and therapeutic promise.}, journal = {Apoptosis : an international journal on programmed cell death}, volume = {}, number = {}, pages = {}, pmid = {40702249}, issn = {1573-675X}, abstract = {Apoptosis signal-regulating kinase 1 (ASK1), a redox-sensitive member of the mitogen-activated protein kinase kinase kinase (MAP3K) family, is a master regulator of neuronal apoptosis as well as neuroinflammation in neurodegenerative disorders (NDs). Under oxidative and endoplasmic reticulum stress conditions, ASK1 sets off a series of pathways, ultimately leading to impairment of cellular functions and the cell's demise. The comprehensive review focuses on the diverse contributions of ASK1 to neurodegeneration driven by Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS). Human and animal evidence links dysregulated ASK1 signaling is related to amyloid deposition, tau hyperphosphorylation, neuroinflammation, abnormal protein folding, and subsequent neurodegeneration. ASK1 plays a role in tau hyperphosphorylation and amyloid-beta-induced neurotoxicity in AD. ASK1-mediated apoptosis of dopaminergic neurons caused by oxidative stress and aggregation of α-synuclein contributes to PD. Furthermore, ASK1 activation is associated with motor neuron degeneration in ALS related to endoplasmic reticulum stress caused by mutant SOD1. Moreover, the pathogenesis of HD involves the activation of ASK1 by the cellular stress caused by mutant huntingtin protein. ASK1 signaling potentiates inflammatory signals in MS because it is involved in demyelination and neuronal injury. Nonetheless, obstacles persist such as developing brain-targeted therapies, reducing adverse systemic effects, and defining disease-stage-specific functions of ASK1. This review aims to comprehensively examine the role of ASK1 signaling in major NDs, discuss its upstream and downstream regulatory mechanisms, and evaluate the current and emerging therapeutic strategies targeting ASK1.}, } @article {pmid40701662, year = {2025}, author = {Toomey, J and Lewis, J and Hannikainen, IR and Earp, BD}, title = {A qualitative study of true self judgments, epistemic access, and medical decision-making.}, journal = {Journal of medical ethics}, volume = {}, number = {}, pages = {}, doi = {10.1136/jme-2025-110957}, pmid = {40701662}, issn = {1473-4257}, abstract = {BACKGROUND: Toomey et al (2024) found that US participants were more likely to follow a medical treatment preference-expressed after substantial cognitive decline-of a third person rather than their own future self. This correlated with a greater tendency to see the third person as still their true self. We hypothesised that the greater epistemic access one has to one's own true self as opposed to others might drive this difference.

METHODS: A codebook designed to capture different kinds of evidence and reasoning was developed, and participants' explanations for their treatment decisions in Toomey et al's study were coded and qualitatively analysed.

RESULTS: In first-person cases, participants were more likely to explain their treatment decision with reference to perceived direct access to their own true self. In contrast, in third-person cases, participants more often relied on proxies or heuristics, such as the presumption that an expressed preference is an authentic one or that preferences expressed with greater cognition tend to better reflect the true self.

CONCLUSIONS: These findings support the hypothesis that differential epistemic access to the true self in first- and third-person cases may drive different medical treatment decisions. Participants may be trying to follow the patient's 'true' or 'authentic' preference in all cases, but relying on different kinds of evidence in so doing.}, } @article {pmid40700505, year = {2025}, author = {Huang, WP and Kumar, V and Yap, K and An, H and John, SJ and Hodgson, RE and Avila, AS and Day, E and Ellis, BCS and Chung, TH and Lord, J and Müller-McNicoll, M and Makeyev, EV and Shelkovnikova, TA}, title = {M6A-dependent RNA condensation underlies FUS autoregulation and can be harnessed for ALS therapy development.}, journal = {Science advances}, volume = {11}, number = {30}, pages = {eadx1357}, pmid = {40700505}, issn = {2375-2548}, mesh = {*RNA-Binding Protein FUS/genetics/metabolism ; *Amyotrophic Lateral Sclerosis/genetics/therapy/metabolism ; Humans ; RNA Splicing ; *Adenosine/analogs & derivatives/metabolism ; Introns ; Mutation ; Methylation ; RNA, Messenger/genetics/metabolism ; *RNA/metabolism/genetics ; RNA Splicing Factors ; Nerve Tissue Proteins ; }, abstract = {Mutations in the FUS gene cause aggressive amyotrophic lateral sclerosis (ALS-FUS). Beyond mRNA, FUS generates partially processed transcripts retaining introns 6 and 7. We demonstrate that these FUSint6&7-RNA molecules form nuclear condensates, scaffolded by the highly structured intron 7 and associated with nuclear speckles. Using hybridization-proximity labeling proteomics, we show that the FUSint6&7-RNA condensates are enriched for splicing factors and the N6-methyladenosine (m6A) reader YTHDC1. These ribonucleoprotein structures facilitate posttranscriptional FUS splicing and depend on m6A/YTHDC1 for integrity. In cells expressing mutant FUS, FUSint6&7-RNAs become hypermethylated, which in turn stimulates their condensation and splicing. We further show that FUS protein is repelled by m6A. Thus, ALS-FUS mutations may cause abnormal activation of FUS posttranscriptional splicing through altered RNA methylation. Notably, ectopic expression of FUS intron 7 sequences dissolves endogenous FUSint6&7-RNA condensates, down-regulating FUS mRNA and protein. Our findings reveal a condensation-dependent mechanism regulating FUS splicing, with possible therapeutic implications for ALS.}, } @article {pmid40700130, year = {2025}, author = {Swindell, WR}, title = {Meta-Analysis of Gene Expression in Bulk-Processed Post-Mortem Spinal Cord from ALS Patients and Normal Controls.}, journal = {NeuroSci}, volume = {6}, number = {3}, pages = {}, pmid = {40700130}, issn = {2673-4087}, abstract = {Amyotrophic lateral sclerosis (ALS) is characterized by upper and lower motor neuron failure and poor prognosis. This study performed a meta-analysis of gene expression datasets that compared bulk-processed post-mortem spinal cord from ALS and control (CTL) patients. The analysis included 569 samples (454 ALS, 115 CTL) from 348 individuals (262 ALS, 86 CTL). Patterns of differential expression bias, related to mRNA abundance, gene length and GC content, were discernable from individual studies but attenuated by meta-analysis. A total of 213 differentially expressed genes (DEGs) were identified (144 ALS-increased, 69 ALS-decreased). ALS-increased DEGs were most highly expressed by microglia and associated with MHC class II, immune response and leukocyte activation. ALS-decreased DEGs were abundantly expressed by mature oligodendrocytes (e.g., the MOL5 phenotype) and associated with myelin production, plasma membrane and sterol metabolism. Comparison to spatial transcriptomics data showed that DEGs were prominently expressed in white matter, with increased DEG expression strongest in the ventral/lateral white matter. These results highlight white matter as the spinal cord region most strongly associated with the shifts in mRNA abundance observed in bulk-processed tissues. These shifts can be explained by attrition of mature oligodendrocytes and an ALS-emergent microglia phenotype that is partly shared among neurodegenerative conditions.}, } @article {pmid40699852, year = {2025}, author = {Takahashi, A and Miyagishi, H and Tsuruta, K and Nango, H and Hirose, D and Aono, Y and Tanigawa, M and Nishimura, K and Saito, M and Kawato, T and Saigusa, T and Kosuge, Y}, title = {Miyako Bidens pilosa Extract Ameliorates Allodynia and Suppresses Spinal Microglial Activation in Mice with Partial Sciatic Nerve Ligation.}, journal = {Current issues in molecular biology}, volume = {47}, number = {6}, pages = {}, pmid = {40699852}, issn = {1467-3045}, support = {2024-2025//Tsuchiya Cultural Foundation/ ; #22Dokusen11//a Nihon University Research Grant/ ; 2024//a grant to encourage and promote research projects at the School of Pharmacy, Nihon University/ ; 24K14758//Japan Society for the Promotion of Science/ ; }, abstract = {Neuropathic pain, characterized by chronic allodynia, remains difficult to manage with current pharmacotherapies. Microglial activation plays a pivotal role in the development and maintenance of neuropathic pain and represents a promising therapeutic target. We previously demonstrated that Miyako Bidens pilosa extract powder (MBP), derived from Miyako Island, Okinawa, suppresses glial activation in a mouse model of amyotrophic lateral sclerosis. In this study, we investigated the analgesic potential of MBP in a mouse model of neuropathic pain. Neuropathic pain was induced in male ICR mice by partial sciatic nerve ligation (PSNL). Mice were orally administered MBP (2 g/kg) or vehicle daily. Mechanical allodynia was assessed using von Frey filaments. On postoperative day 7, MBP-treated mice exhibited significantly reduced allodynia compared to vehicle-treated mice. MBP also attenuated thermal hyperalgesia on postoperative day 7. Lumbar spinal cords (L5) were subjected to immunohistochemical analysis for ionized calcium-binding adaptor molecule 1 (Iba1), a microglial marker. MBP significantly decreased the number of Iba1-positive microglia in the ipsilateral dorsal horn. These results suggest that MBP alleviates neuropathic pain, at least in part, by suppressing microglial activation in the spinal cord. MBP may represent a novel plant-derived therapeutic candidate for treating neuropathic pain.}, } @article {pmid40699841, year = {2025}, author = {Long, X and Wang, Y and Meng, H}, title = {Dicer Is Involved in Cytotoxicity and Motor Impairment Induced by TBPH Deficiency.}, journal = {Current issues in molecular biology}, volume = {47}, number = {6}, pages = {}, pmid = {40699841}, issn = {1467-3045}, support = {82171414//National Natural Science Foundation of China/ ; 2022SS02//Suzhou Science and Technology Plan Projec/ ; }, abstract = {TDP-43 is an RNA-binding protein linked to amyotrophic lateral sclerosis (ALS), possibly associated with a role in miRNA biogenesis, which is still not fully understood. Herein we investigated the impact of the Drosophila homolog of TDP-43, TBPH, on genes related to miRNA biogenesis. A TBPH knockout significantly reduced mRNA transcription and protein levels of DCR-1 and DCR-2, whereas an overexpression of DCR-1 and DCR-2 in a TBPH knockdown background exacerbated compound eye damage, with variations in severity that were sex-dependent. Neuronal TBPH RNAi consistently shortened lifespan, with males and females exhibiting distinct survival profiles. DCR-1 and DCR-2 knockdown worsened the locomotor defects induced by TBPH deficiency, thus reinforcing the functional link between TBPH and DCR. In TBPH-deficient flies, the pharmacological activation of Dicer promoted reverse locomotion behavior, with a preference for backward movement. Overall, we show that TBPH is a key regulator of DCR protein expression, highlighting its conserved role in miRNA dysregulation associated with motor function and cytotoxicity in ALS-like pathology in Drosophila models.}, } @article {pmid40699743, year = {2025}, author = {Wang, S and Pan, L and Sun, C and Ma, C and Pan, H}, title = {Balancing Microglial Density and Activation in Central Nervous System Development and Disease.}, journal = {Current issues in molecular biology}, volume = {47}, number = {5}, pages = {}, pmid = {40699743}, issn = {1467-3045}, support = {32260194 to S.Wang, and 82071245 and 82360238 to H.Pan//National Natural Science Foundation of China/ ; 20224BAB206038 to S.Wang, 20224BAB206042 to C.Sun, and 20202ACB215003 and 20232ACB205008 to H.Pan//Natural Science Foundation of Jiangxi Province/ ; }, abstract = {Microglia, the resident immune cells of the central nervous system, play multifaceted roles in both health and disease. During development, they regulate neurogenesis and refine neural circuits through synaptic pruning. In adulthood, microglia maintain homeostasis and dynamically respond to pathological insults, where they contribute to responding to neuroinflammatory challenges. This review summarizes microglial contributions to neurodevelopment and also outlines their function across various neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis, highlighting both protective and detrimental effects. Finally, recent advances in microglial-targeted therapies and lifestyle-based interventions are highlighted, underscoring the translational potential of modulating microglial states. Elucidating the dual roles of microglia in development and disease could guide the design of therapeutic strategies aimed at enhancing neuroprotection while minimizing neurotoxicity.}, } @article {pmid40699658, year = {2025}, author = {Brezic, N and Gligorevic, S and Sic, A and Knezevic, NN}, title = {Protein Misfolding and Aggregation as a Mechanistic Link Between Chronic Pain and Neurodegenerative Diseases.}, journal = {Current issues in molecular biology}, volume = {47}, number = {4}, pages = {}, pmid = {40699658}, issn = {1467-3045}, abstract = {Chronic pain, defined by persistent pain beyond normal healing time, is a pervasive and debilitating condition affecting up to 30-50% of adults globally. In parallel, neurodegenerative diseases (NDs) such as Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS) are characterized by progressive neuronal loss and cognitive or motor decline, often underpinned by pathological protein misfolding and aggregation. Emerging evidence suggests a potential mechanistic link between chronic pain and NDs, with persistent pain contributing to neuroinflammatory states and protein homeostasis disturbances that mirror processes in neurodegeneration. This review explores the hypothesis that protein misfolding and aggregation serve as a mechanistic bridge between chronic pain and neurodegeneration. We systematically examine molecular pathways of protein misfolding, proteostasis dysfunction in chronic pain, and shared neuroimmune mechanisms, highlighting prion-like propagation of misfolded proteins, chronic neuroinflammation, and oxidative stress as common denominators. We further discuss evidence from experimental models and clinical studies linking chronic pain to accelerated neurodegenerative pathology-including tau accumulation, amyloid dysregulation, and microglial activation-and consider how these insights open avenues for novel therapeutics. Targeting protein aggregation, enhancing chaperone function, modulating the unfolded protein response (UPR), and attenuating glial activation are explored as potential strategies to mitigate chronic pain and possibly slow neurodegeneration. Understanding this intersection not only elucidates chronic pain's role in cognitive decline but also suggests that interventions addressing proteostasis and inflammation could yield dual benefits in pain management and neurodegenerative disease modification.}, } @article {pmid40698100, year = {2025}, author = {Singh, D and Singhal, S and Kanaujiya, V and Ranjan, A and Mani, VE and Paliwal, VK and Jain, V and Aishwarya, A and Agarwal, R}, title = {Ganglion Cell Layer Thickness as a Biomarker for Amyotrophic Lateral Sclerosis Functional Outcome: An OCT study.}, journal = {Romanian journal of ophthalmology}, volume = {69}, number = {2}, pages = {200-207}, pmid = {40698100}, issn = {2501-2533}, mesh = {Humans ; *Tomography, Optical Coherence/methods ; *Amyotrophic Lateral Sclerosis/physiopathology/diagnosis ; Male ; Middle Aged ; Female ; *Retinal Ganglion Cells/pathology ; *Visual Acuity/physiology ; *Nerve Fibers/pathology ; Adult ; *Optic Disk/pathology ; Aged ; Intraocular Pressure/physiology ; Biomarkers ; }, abstract = {AIM: This study aims to evaluate various optical coherence tomography (OCT) parameters in patients diagnosed with amyotrophic lateral sclerosis (ALS).

METHODS: Assessment of BCVA was done using Snellen charts, and subjective refraction was done to achieve a BCVA for distance and near. Measurement of intraocular pressure (IOP) was done with Goldman applanation tonometry. Stereoscopic fundus examination was performed using a 90D lens to assess the status of the optic nerve and retina, ruling out any ocular pathology. The patients were then subjected to OCT scanning to measure optic nerve head and macular parameters. Optical coherence tomography was performed using CIRRUS™ HD OCT (500-21822) (version 8.0.0.518) (Carl Zeiss Meditec, Dublin, CA, USA). The analyzed area was centered manually, and the absence of segmentation errors was confirmed for each scan.

RESULTS: RE Avg RNFL and LE Avg RNFL showed weak correlations with ALSFRS, indicated by Pearson Correlation coefficients of 0.073 and -0.026, respectively. The p-values (0.637 and 0.86) suggested that these correlations were not statistically significant. RE Avg GCL and LE Avg GCL, on the other hand, exhibited moderate positive correlations with ALSFRS scores, with correlation coefficients of 0.337 (RE) and 0.389 (LE). These correlations were statistically significant, as indicated by p-values of 0.021 and 0.006, respectively, suggesting a substantial association between GCL thickness and ALS functional outcomes.

DISCUSSION: All patients in our study were clinically diagnosed cases of ALS, as per the El Escorial criteria. Age group-wise analysis showed statistically significant thinning overall as well as quadrant-wise RNFL parameters in patients less than 50 years compared to age-matched controls, indicating that the pathological process occurring in larger motor neurons in ALS might also be happening in smaller sensory neurons of the retina, causing thinning, which was not due to age-related process. Although GCIPL thinning was occurring in our cases, though statistically not significant compared to control, the significant positive correlation observed between GCIPL and ALS functional outcome and between RNFL and GCIPL measurements highlighted the fact that though the axonal degeneration in retinal neurons might not be translating to the same extent in ganglion cells in ALS, the subtle thinning of GCIPL correlated strongly with functional disability in patients with ALS, implying better functional scores with higher values of GCIPL parameters.

CONCLUSION: In summary, GCL measurements in both eyes showed a notable relationship with ALSFRS, whereas RNFL did not appear to correlate significantly.}, } @article {pmid40697273, year = {2025}, author = {Gomes-Duarte, A and Pascoal, S and Haselberg, R and Sogorb-Gonzalez, M and van Deventer, S}, title = {Targeting oxidized phosphatidylcholines in SOD1-associated ALS: therapeutic potential of PC-OxPL-VecTab[®].}, journal = {Frontiers in neuroscience}, volume = {19}, number = {}, pages = {1620181}, pmid = {40697273}, issn = {1662-4548}, abstract = {Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by progressive motor neuron degeneration. Mutations in the superoxide dismutase 1 (SOD1) gene account for a significant fraction of familial ALS (fALS) cases. Oxidative stress and oxidized phosphatidylcholines (PC-OxPL) contribute to neuroinflammation and neuronal damage, and to motor neuron degeneration in ALS. We previously demonstrated the therapeutic efficacy of an AAV-delivered anti-PC-OxPL single-chain variable fragment (PC-OxPL-VecTab[®]) in neutralizing PC-OxPL toxicity in the periphery and central nervous system (CNS), but the therapeutic potential of PC-OxPL-VecTab[®] has not been investigated in the context of fALS and SOD1-associated ALS. We report that PC-OxPL accumulation contributes to the pathological phenotypes associated with SOD1[G93A] iPSC-derived motor neurons and the corresponding mouse model. The current findings further demonstrate that PC-OxPL-VecTab[®] is efficacious in neutralizing the downstream effects of SOD1-associated PC-OxPL accumulation, such as altered gene expression and axonal health in SOD1 motor neurons, as well as a pathological lipid profile in the SOD1[G93A] mouse model. Collectively, the present study underscores the significance of PC-OxPL dysfunction in the context of SOD1 genotypes and sheds light on the potential of PC-OxPL-VecTab® for therapeutically targeting ALS.}, } @article {pmid40696471, year = {2025}, author = {Lin, CF and Chen, YH and Yeh, CC and Hsu, SPC and Fu, YS}, title = {Xenotransplantation of Human Umbilical Mesenchymal Stromal Cells Derived from Wharton's Jelly Mitigates Mouse Amyotrophic Lateral Sclerosis.}, journal = {Stem cell research & therapy}, volume = {16}, number = {1}, pages = {395}, pmid = {40696471}, issn = {1757-6512}, support = {V114C-203//Taipei Veterans General Hospital/ ; 113-2314-B-075-061//National Science and Technology Council in Taiwan/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/therapy/pathology ; Animals ; Humans ; *Mesenchymal Stem Cells/cytology/metabolism ; *Mesenchymal Stem Cell Transplantation ; Mice ; Mice, Transgenic ; Superoxide Dismutase-1 ; *Wharton Jelly/cytology ; Spinal Cord/pathology ; Transplantation, Heterologous ; Superoxide Dismutase/genetics/metabolism ; Umbilical Cord/cytology ; Motor Neurons/pathology ; Disease Models, Animal ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a motor neuron disease characterized by progressive degeneration of motor neurons in the cerebral cortex, brainstem, and spinal cord, eventually leading to paralysis, respiratory failure, and death. Currently, no effective treatment exists for ALS.

METHODS: This study examined the therapeutic potential of human umbilical cord mesenchymal stromal cells (HUMSCs) by transplanting 2 × 10⁶ HUMSCs into the spinal canal of transgenic mice expressing mutant human superoxide dismutase 1 (SOD1) at 8 weeks of age.

RESULTS: Survival analysis showed that the SOD1 group lived up to 171 days, while the SOD1 + HUMSCs group survived up to 199 days, extending lifespan by 17 days on average. Motor function tests, including rotarod performance, grip strength, open field activity, and balance beam tests, demonstrated that while the SOD1 group experienced progressive decline, the SOD1 + HUMSCs group showed improvement. Electrophysiological assessments at 20 weeks of age revealed weak muscle action potential in the SOD1 group, whereas the SOD1 + HUMSCs group exhibited noticeable improvements. Histological analysis indicated significant spinal cord atrophy in the SOD1 group, while HUMSCs transplantation mitigated this degeneration. Moreover, HUMSCs reduced blood-spinal cord barrier leakage and T lymphocyte infiltration, alleviating inflammation. The number and size of activated microglia and astrocytes increased in the SOD1 group but were reduced with HUMSCs treatment. Additionally, HUMSCs preserved more motor neurons in the anterior horns.

CONCLUSION: Collectively, transplantation of HUMSCs effectively reduced inflammatory reaction in spinal cord, decreased loss of neurons, ameliorated disease deterioration, and extended life span, suggesting that it could serve as a new direction of ALS treatment to improve patients' quality of life or behavioral function.}, } @article {pmid40694827, year = {2025}, author = {Berry, J and Raymond, J and Larson, T and Horton, DK and Han, M and Nair, T and Al-Chalabi, A and Mehta, P}, title = {Amyotrophic Lateral Sclerosis as a Multistep Process in the United States: A Population-Based Study.}, journal = {Annals of clinical and translational neurology}, volume = {}, number = {}, pages = {}, doi = {10.1002/acn3.70096}, pmid = {40694827}, issn = {2328-9503}, support = {/CC/CDC HHS/United States ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a fatal, progressive neurodegenerative disease that typically results in death within 3-5 years from symptom onset. However, little is known about the environmental exposures, clinical aspects, or social determinants of health factors that may be associated with the disease. Multistep modeling has been previously applied to cancer research, demonstrating a linear relationship between logs of incidence and age. This method may help to understand the mechanisms involved in the development of ALS in the United States (e.g., environmental exposures, genetic mutations). We aim to assess whether ALS is a multistep process among patients enrolled in the largest ALS registry in the world-the United States' National ALS Registry.

METHODS: Incident ALS cases, defined as confirmed and likely, cases between 2012 and 2019 were obtained from the National ALS Registry. Age-standardized incidence was calculated for all cases and by sex. The log incidence of ALS was regressed against the log of age (years) at case determination, on average, for each year and by sex.

FINDINGS: Between 2012 and 2019, there was a mean of 5253 incident ALS cases (confirmed or likely) per year. We identified a linear relationship between the log of the average incidence and log age overall (r[2] = 0.99), for men (r[2] = 0.99), and for women (r[2] = 0.98). The incidence slope estimates were 4.8 (95% CI: 4.4-5.1) overall, 4.7 (95% CI: 4.4-5.1) for men, and 5.0 (95% CI: 4.5-5.5) for women.

INTERPRETATION: The linear relationships observed overall, for men, and for women are consistent with a multi-step process. The slope estimates, on average, are approximately 5.0, which suggests that the development of ALS is a six-step process. Further investigation of these steps can elucidate potential risk factors and treatments for ALS.}, } @article {pmid40693147, year = {2025}, author = {Mageto, LM and Aboge, GO and Mekuria, ZH and Gathura, P and Juma, J and Mugo, M and Kebenei, CK and Imoli, D and Ongadi, BA and Kering, K and Mbae, CK and Kariuki, S}, title = {Genomic characterization of Vibrio cholerae isolated from clinical and environmental sources during the 2022-2023 cholera outbreak in Kenya.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1603736}, pmid = {40693147}, issn = {1664-302X}, abstract = {BACKGROUND: Cholera remains a public health challenge in Kenya. To better understand its dynamics, we analyzed Vibrio cholerae genomes from clinical and environmental samples collected during the 2022-2023 outbreak. These strains were compared with historical genomes from Kenya, Uganda, Tanzania, and Haiti to inform strategies for cholera prevention, control, and elimination in Kenya.

METHODS: Clinical (stool) and environmental (wastewater, drinking water, and household effluent) samples were collected from Nairobi county. Samples were analyzed for V. cholerae using culture and real time PCR. The environmental (n = 17) and clinical (n = 70) isolates were then subjected to phenotypic antimicrobial susceptibility testing using the Kirby-Bauer disk diffusion method. Whole genome sequencing was employed to characterize the genome, detect antimicrobial resistance genes, virulence factors, and mobile genetic elements. Phylogenetic analysis was performed to assess the genetic relationship and diversity of isolates from 2022 to 2023 outbreak, comparing them with isolates from historical outbreaks.

RESULTS: Clinical isolates carried key virulence genes (ctxA, ctxB7, zot, and hlyA) and were 100% resistant to multiple antibiotics, including ampicillin, cefotaxime, ceftriaxone, and cefpodoxime, but remained susceptible to gentamicin and chloramphenicol. In contrast, environmental isolates lacked ctxB gene but harbored toxR, als, and hlyA, showing variable antibiotic resistance (59% to ampicillin, 41% to trimethoprim-sulfamethoxazole, and 47% to nalidixic acid). All clinical isolates from 2022 to 2023 outbreak harbored IncA/C2 plasmids and several antimicrobial resistance genes including bla PER-7. Phylogenetic analysis revealed high genetic diversity in environmental strains, clustering outside the 7th pandemic El Tor lineage, while clinical isolates were highly clonal. Genomes from 2022 to 2023 outbreak were closely related to Kenyan cholera outbreak genomes from 2016 (15 single nucleotide polymorphisms, T13 lineage).

CONCLUSION: The 2022-2023 outbreak likely resulted from re-emergence of previously circulating strains rather than a new introduction. While the role of environmental reservoirs as a source of human infection remains unclear in our study, environmental isolates possess virulent and antimicrobial resistance genes that may spread via horizontal gene transfer. This highlights the need for continuous genomic surveillance to monitor V. cholerae evolution, track transmission patterns, and mitigate the spread of antimicrobial resistance.}, } @article {pmid40692425, year = {2025}, author = {Yang, Z and Wu, Y and Gao, J and Hu, S and Wang, J and Jing, R}, title = {Comparison of the Peripapillary Structure-Vessel Density Relationship Before and After Axial Length Magnification Correction Using Different Methods.}, journal = {Clinical & experimental ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1111/ceo.14585}, pmid = {40692425}, issn = {1442-9071}, support = {2023HXKT033//Horizontal Project/ ; 2024HXKT054//Horizontal Project/ ; (QN)202302//The Youth fund of The Second Affiliated Hospital of Xi'an Jiaotong University/ ; }, abstract = {BACKGROUND: To evaluate changes in OCTA-derived structural and vascular parameters before and after axial length (AL) magnification correction using two different formulas, and to explore their correlations with vessel density (VD).

METHODS: This study included 45 high myopic eyes and 45 age- and gender-matched controls. Both 6 × 6 mm[2] optic nerve head imaging and biological measurement were performed using OCTA. Magnification correction was performed using both the Bennett formula and the device's built-in algorithm. Parameters analysed included retinal nerve fibre layer (RNFL) thickness, superficial vascular complex (SVC) VD, deep vascular complex (DVC) VD, and choroidal VD.

RESULTS: In long AL eyes, uncorrected values underestimated RNFL thickness and SVC VD but overestimated DVC VD and choroidal VD; discrepancies increased with AL. The opposite pattern was observed in shorter eyes. After correction, all vascular parameters except DVC VD showed significant changes in the high myopia group, while non-high myopic eyes showed no significant differences. The two correction methods showed strong agreement across all layers. RNFL thickness correlated strongly with SVC VD, and choroidal thickness (CT) with choroidal VD, both before and after correction. Post-correction, AL was no longer associated with RNFL thickness or SVC VD, while its correlation with CT and choroidal VD persisted. Mediation analysis showed AL fully mediated the CT-choroidal VD relationship, with a stronger effect post-correction.

CONCLUSIONS: Magnification correction is crucial in high myopic eyes. Both formulas showed high consistency. Correction eliminated AL's confounding effects on RNFL and SVC VD, while emphasising its mediating role between CT and choroidal VD.}, } @article {pmid40691976, year = {2025}, author = {Pandey, P and Das, R and Yadav, H and Mukherjee, A and Mutsuddi, M}, title = {RNA helicase maheshvara interacts with TDP-43 and exacerbates neurodegeneration in Drosophila model of amyotrophic lateral sclerosis.}, journal = {Neurobiology of disease}, volume = {214}, number = {}, pages = {107036}, doi = {10.1016/j.nbd.2025.107036}, pmid = {40691976}, issn = {1095-953X}, abstract = {Drosophila maheshvara (mahe) encodes a conserved DEAD box RNA helicase that regulates various important signaling pathways like Notch and JAK/STAT, pathways that have been functionally implicated in neuronal development. In order to identify novel modulators of mahe as well as to unravel its role in neurodegenerative disorders, a genetic modifier screen using Drosophila models of neurodegenerative disorders was carried out. From this screen, we identified mahe to be a potent modifier of TDP-43 mediated proteinopathy in Drosophila model of Amyotrophic Lateral Sclerosis (ALS). We demonstrate that Mahe genetically interacts and associates with cytosolic hyperphosphorylated toxic aggregates of TDP-43 leading to enhanced TDP-43 mediated neurodegenerative phenotype. Increased autophagy, cytoskeletal disruption, and FMRP-mediated translational repression of neuronal target Futsch were observed, potentially contributing to neuronal dysfunction. The current study indicates a strong interaction of mahe and TDP-43 (TARDBP) resulting in augmentation of TDP-43 mediated neurodegenerative phenotypes which parallels ALS clinical pathology.}, } @article {pmid40691077, year = {2025}, author = {Dinh, TTH and Imura, C and Shiokawa, M and Ayabe, S and Yoshiki, A and Inoue, H and Amano, T}, title = {A partial deletion of the Tardbp 3´UTR affects TDP-43 regulation and leads to motor dysfunction in mice.}, journal = {Experimental animals}, volume = {}, number = {}, pages = {}, doi = {10.1538/expanim.25-0061}, pmid = {40691077}, issn = {1881-7122}, abstract = {Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease that causes the selective loss of motor neurons. A histopathological hallmark of ALS is the cytoplasmic aggregation of TDP-43, a ubiquitously expressed RNA-binding protein involved in transcription and splicing regulation. To prevent abnormal accumulation, TDP-43 controls its expression levels through an autoregulatory feedback loop. While most ALS studies have focused on pathogenic variants that impair the protein function of TDP-43, the mechanisms underlying endogenous TDP-43 dysregulation mediated by non-coding elements, including the 3´ untranslated region (3´UTR), remain incompletely understood. In this study, we generated a mouse model carrying a targeted deletion of the Tardbp 3´UTR that encompasses the TDP-binding region, polyadenylation signals, and alternative intronic sequences. Our findings demonstrate that the Tardbp 3´UTR is essential for normal mouse development. Loss of this region led to decreased Tardbp mRNA expression and embryonic lethality after gastrulation. Young heterozygous mice were phenotypically normal with no overt disruption in TDP-43 autoregulation. However, aged heterozygous mice displayed mild locomotor dysfunction accompanied by a modest increase in spinal cord TDP-43 protein levels and a reduction in motor neuron numbers. These findings indicate that regulatory elements within the Tardbp 3´UTR play a pivotal role in normal development and contribute to TDP-43 pathology relevant to ALS.}, } @article {pmid40690048, year = {2025}, author = {Palumbo, F and Iazzolino, B and Moglia, C and Manera, U and Matteoni, E and Cabras, S and Brunetti, M and Gallone, S and Callegaro, S and Vasta, R and Mora, G and De Marchi, F and Corrado, L and D'Alfonso, S and Mazzini, L and Canosa, A and Grassano, M and Calvo, A and Chiò, A}, title = {Exploring the phenotypic fingerprints of ANXA11 variants in ALS: a population-based study in an European cohort.}, journal = {Journal of neurology}, volume = {272}, number = {8}, pages = {524}, pmid = {40690048}, issn = {1432-1459}, support = {RF-2016-02362405//Ministero della Salute/ ; 2017SNW5MB//Ministero dell'Università e della Ricerca/ ; 20228N7573//Ministero dell'Università e della Ricerca/ ; 259867//Seventh Framework Programme/ ; 101017598//H2020 Health/ ; 101137074//HORIZON EUROPE Framework Programme/ ; DIG-ALS//ARISLA/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/epidemiology/complications/physiopathology ; Male ; Female ; Middle Aged ; Aged ; *Annexins/genetics ; Cohort Studies ; *Cognitive Dysfunction/genetics/epidemiology/etiology ; Phenotype ; Italy/epidemiology ; Adult ; C9orf72 Protein/genetics ; Registries ; }, abstract = {BACKGROUND: Annexin A11 (ANXA11) has emerged as a significant gene associated with amyotrophic lateral sclerosis (ALS) and cognitive impairments. This study aimed to evaluate the prevalence and clinical and cognitive features of pathogenic variants in ANXA11 in an Italian ALS cohort.

METHODS: Data were collected from the Piemonte and Valle d'Aosta Register for ALS between 2009 and 2020. Only patients who underwent whole genome sequencing (WGS) were included. Clinical and cognitive assessments were compared among patients with ANXA11-ALS, wild-type ALS (WT-ALS), and C9ORF72-ALS.

RESULTS: Among 1,486 ALS patients, 18 (1.4%) were found to carry ANXA11 variants, four of which were classified as benign or likely benign. Three patients (16.7%) also had co-occurring variants in ERBB4 (erb-b2 receptor tyrosine kinase 4), EPHA4 (ephrin type-A receptor 4), or C9ORF72 (chromosome 9 open reading frame 72). Patients with ANXA11-ALS had significantly lower education levels (6.2 vs. 8.9 years), higher BMI at diagnosis (26.7 vs. 24.5), and a higher prevalence of cognitive impairment (100% vs. 47%) compared to WT-ALS. Cognitive testing revealed more severe deficits in executive function, attention, psychomotor speed, non-verbal intelligence, and cognitive flexibility, though no behavioral differences were observed. Compared to C9ORF72-ALS, ANXA11-ALS patients were older at diagnosis (66.6 vs. 60.3 years), had lower education levels (6.2 vs. 9.0 years), and higher rates of cognitive impairment (100% vs. 68.7%).

DISCUSSION: Pathogenic ANXA11 variants are relatively common in ALS and are strongly associated with cognitive impairment. Including ANXA11 in routine genetic screening may enhance diagnostic precision and therapeutic strategies for ALS patients.}, } @article {pmid40689468, year = {2025}, author = {Costello, E and De Vocht, J and Beswick, E and Mac Domhnaill, É and Peelo, C and Foucher, J and Mayberry, EJ and Chiwera, T and Hiemstra, F and Caravaca Puchades, A and Iazzolino, B and Palumbo, F and Alves, I and Kasper, E and Galvin, M and Heverin, M and Ingre, C and Mcdermott, CJ and Shaw, P and Al-Chalabi, A and Van Den Berg, LH and Povedano Panadés, M and Chiò, A and Carvalho, M and Bencheikh, S and Corcia, P and Mouzouri, M and Hermann, A and Abrahams, S and Pender, N and Van Damme, P and Hardiman, O}, title = {Neuropsychological assessment practices in PRECISION-ALS: challenges and opportunities for harmonization.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {}, number = {}, pages = {1-10}, doi = {10.1080/21678421.2025.2527877}, pmid = {40689468}, issn = {2167-9223}, abstract = {OBJECTIVE: To gather comprehensive insights regarding current neuropsychological assessment practices in PRECISION-ALS, a pan-European research and industry consortium, to propose areas which can be harmonized and facilitate more robust cross-country comparisons.

METHODS: Representatives from PRECISION-ALS sites were surveyed with a semi-structured interview, gathering information on how people with ALS are assessed for cognitive/behavioral change, including how they are initially screened, classified as impaired/unimpaired, and followed up longitudinally. Assessment practices across PRECISION-ALS sites were summarized using descriptive analysis.

RESULTS: Ten of the eleven PRECISION-ALS sites perform cognitive and/or behavioral screening at least once during the course of the disease, using the Edinburgh Cognitive and Behavioral ALS Screen, either for clinical or research purposes. All centers categorize impairment, but differ how it is defined, with some using local norms, and others using other countries' norms. Most sites account for age and education, but differ in how these factors are considered. Longitudinal protocols vary in terms of the number of assessments, time intervals, and use of alternative versions. Behavioral screening is more consistently implemented, with the ECAS caregiver interview as the standard tool, however there is a lack of clarity in how this data is applied. Many sites supplement cognitive and behavioral screening with additional measures of mood and/or neuropsychiatric symptoms.

CONCLUSIONS: These findings illustrate areas of commonality and divergence in neuropsychological screening practices. Site-specific variations are likely to confound research involving cross-country data-sharing. PRECISION-ALS, in generating prospective population-based datasets, will provide agreed harmonized protocols for neuropsychological assessment across participating sites.}, } @article {pmid40689424, year = {2025}, author = {Poletti, B and Aiello, EN and Curti, B and Torre, S and De Luca, G and D'Ambrosio, C and Gendarini, C and Cocuzza, A and Colombo, E and Maranzano, A and Verde, F and Morelli, C and Messina, S and Doretti, A and Monti, A and Silani, V and Ticozzi, N}, title = {Unraveling the contribution of executive functions to language impairment in ALS.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {}, number = {}, pages = {1-9}, doi = {10.1080/21678421.2025.2529409}, pmid = {40689424}, issn = {2167-9223}, abstract = {Objectives: This study aims to unravel the association between language deficits and executive functions in non-demented amyotrophic lateral sclerosis (ALS) patients by means of 1) assessing the executive determinants of language impairment (LI) and 2) simultaneously testing the effects of both executive and language performances on phonemic verbal fluency (PVF) deficits. Methods: N = 299 non-demented ALS patients underwent the Edinburgh Cognitive and Behavioral ALS Screen (ECAS), being also assessed for behavioral/psychiatric and motor-functional features. Two sets of logistic models were run: the first, regressing an impaired vs. unimpaired performance on each ECAS-Language (ECAS-L) tasks based on each task of the ECAS-Executive Functioning (ECAS-EF); the second, regressing an impaired vs. unimpaired performance on each ECAS-Fluency tasks based on both ECAS-L and ECAS-EF tasks. Within these models, demographic, motor-functional, and psychiatric/behavioral measures were covaried for. Results: Defective Naming and Comprehension performances were predicted by lower scores on the Sentence Completion task (p ≤ 0.002), whilst defective Spelling performances by lower Alternation scores (p < 0.001). Defective performances on Verbal fluency - S and Verbal fluency - C tasks were predicted by lower Backward Digit Span and Sentence Completion scores, respectively (p ≤ 0.008). Discussion: In ALS patients, inhibitory and set-shifting abilities majorly contribute to LI, whilst PVF deficits are mostly linked to dysexecutive features.}, } @article {pmid40689409, year = {2025}, author = {El Haj, M and Hallit, S and Boutoleau-Bretonnière, C}, title = {Pupil response as a window into cognitive processing in amyotrophic lateral sclerosis.}, journal = {eNeurologicalSci}, volume = {40}, number = {}, pages = {100575}, pmid = {40689409}, issn = {2405-6502}, abstract = {PURPOSE: This preliminary study aimed to investigate whether the pupil size reflects cognitive load in patients with amyotrophic lateral sclerosis (ALS).

METHODS: Pupil activity was monitored in three patients with ALS and a group of healthy control participants (n = 16) while performing three tasks: a forward span task, a backward span task, and a control task involving counting aloud. These tasks were designed to impose increasing cognitive demands, with the backward span task being the most challenging.

RESULTS: Analysis revealed no significant difference in pupil size between patients with ALS and controls for the forward or backward spans or the control condition. Both groups demonstrated a consistent pattern of increased pupil size during the backward span task compared to the forward span task, and during the forward span task compared to the control condition.

CONCLUSION: These findings suggest that pupil dilation reflects task-related cognitive load similarly in ALS patients and healthy controls. This supports the use of pupillometry as a non-invasive and sensitive marker of cognitive processing in ALS.}, } @article {pmid40689333, year = {2025}, author = {Tian, M and Xin, C and Huo, J and Liu, Q and Dong, H and Bai, L and Wang, Y and Li, R and Liu, Y}, title = {Unlocking amyotrophic lateral sclerosis: the role of adiponectin in inflammation and disease progression.}, journal = {Frontiers in neurology}, volume = {16}, number = {}, pages = {1605822}, pmid = {40689333}, issn = {1664-2295}, abstract = {INTRODUCTION: In amyotrophic lateral sclerosis (ALS), immune cells become activated, resulting in a persistent pro-inflammatory milieu and contributing to the development of ALS. Adiponectin produces anti-inflammatory effects via its adiponectin receptor 1 (AdipoR1) and adiponectin receptor 2 (AdipoR2). Currently, there has been limited research conducted on the correlation between adiponectin and inflammation in ALS.

METHODS: This cross-sectional study recruited a cohort of 82 ALS patients and 25 controls. Adiponectin and inflammatory mediators in plasma were measured using enzyme-linked immunosorbent assay (ELISA). Furthermore, flow cytometry, immunocytochemistry, and ELISA were employed to examine the levels of AdipoR1, AdipoR2, and inflammatory markers in monocytes and macrophages obtained from ALS patients. The effects of Adiponectin receptor agonists (AdipoRon) on AdipoR expression, inflammatory responses, and macrophages polarization were investigated.

RESULTS: Plasma adiponectin level in ALS patients was markedly lower than controls. This decrease was found to be positively associated with IL-1β, IL-2, IL-6, IL-8, and TNF-α, while negatively correlated with IL-4 and IL-10. Furthermore, there was a positive correlation between plasma adiponectin level and ALS Functional Rating Scale-Revised (ALSFRS-R), and a negative correlation with the disease progression rate (δFS). Mediation research demonstrated that IL-2, or TNF-α, or IL-10 acted as a mediator between adiponectin and δFS. AdipoR1 and AdipoR2 showed a notable increase in expression in peripheral blood monocytes and activated macrophages obtained from ALS patients, concomitant with elevated level of IL-1β. AdipoRon treatment resulted in a decrease in the expression of AdipoR1. Simultaneously, AdipoRon decreased the levels of IL-1β and MHC-II, while boosting the levels of IL-10 and CD206. This regulation enabled the transformation of macrophages from the M1 to the M2 phenotype, therefore aiding in the protection of neurons.

CONCLUSION: Our findings demonstrated a notable association between adiponectin level and inflammation in the peripheral regions of ALS patients. These results may offer new understanding into the control of inflammation and propose a possible treatment approach for ALS.}, } @article {pmid40688669, year = {2025}, author = {Zhu, RK and Shi, J and Zhou, HJ and Ge, L and Yin, WH and Zeng, H and Wang, XW}, title = {Biological applications of graphene-based nanomaterials in neurodegenerative diseases.}, journal = {Materials today. Bio}, volume = {33}, number = {}, pages = {102064}, pmid = {40688669}, issn = {2590-0064}, abstract = {Neurodegenerative diseases (NDDs) have become a major challenge in global public health due to neurotoxicity caused by progressive neuronal degeneration and abnormal protein aggregation, which has attracted widespread attention. Graphene-based nanomaterials provide innovative solutions for the early diagnosis and precise treatment of NDDs by virtue of their ultra-high conductivity, large specific surface area and multifunctional properties. In this paper, we systematically discuss the key applications of these materials in the diagnosis and treatment of NDDs, and deeply analyze the technological breakthroughs and clinical translation challenges. The core of this paper is to illustrate that graphene-based nanomaterials are expected to reshape the paradigm of NDDs diagnosis and treatment through cross-scale technological innovations, promoting the synergistic development of early diagnosis, personalized treatment and real-time monitoring, and providing a transformative strategy for overcoming NDDs.}, } @article {pmid40687373, year = {2025}, author = {Hollensen, AK and Sørensen, MH and Thomsen, SV and Thomsen, HS and Damgaard, CK}, title = {Using circular RNAs to target toxic RNA-binding proteins in amyotrophic lateral sclerosis.}, journal = {Molecular therapy. Methods & clinical development}, volume = {33}, number = {3}, pages = {101525}, pmid = {40687373}, issn = {2329-0501}, abstract = {Amyotrophic lateral sclerosis (ALS) is characterized by motor neuron degeneration and is in many cases associated with mutations in genes encoding RNA-binding proteins (RBPs), including fused in sarcoma (FUS) and heterogeneous nuclear ribonuclearprotein A1 (hnRNPA1). These mutations often cause cytoplasmic mislocalization and aggregation of these typically nuclear proteins. Current treatment options for ALS are limited, highlighting the need for new therapeutic strategies. Here, we demonstrate an approach using circular RNAs (circRNAs) to target disease-associated RBPs for degradation. We designed circRNAs containing binding sites for both the target RBPs (FUS or hnRNPA1) and ring finger and CCCH-type domains 2 (RC3H2), an RNA-binding E3 ubiquitin ligase. Through RNA immunoprecipitations and protein analyses, we show that these circRNAs can form ternary complexes with their target RBPs and RC3H2. Importantly, we observed significant reductions in steady-state protein levels of ALS-associated FUS-P525L (20%) and hnRNPA1-P288S (30%) mutants when treated with their respective targeting circRNAs. These findings provide proof of concept for using circRNAs as scaffolds to promote the degradation of disease-associated RBPs, establishing a foundation for developing advanced RNA-based therapeutic strategies for ALS and potentially other RBP-related diseases.}, } @article {pmid40685584, year = {2025}, author = {Young, CA and Chaouch, A and Mcdermott, CJ and Al-Chalabi, A and Chhetri, SK and Waters, N and Buccleuch, R and Mills, RJ and Tennant, A and , }, title = {Patient reported outcome measures require scale metrification and quantified precision: evidence from the assessment of breathlessness in people with ALS/MND.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {}, number = {}, pages = {1-7}, doi = {10.1080/21678421.2025.2533870}, pmid = {40685584}, issn = {2167-9223}, abstract = {Introduction: Precision (how closely repeated measures match) and responsiveness (ability to detect change over time) are critical properties of patient reported outcome measures (PROMs). Smallest Detectable Difference (SDD) is a useful statistic regarding precision; Minimal Detectable Change (MDC) and Minimal Important Change (MIC) assess responsiveness. Methods: We examined measurement properties of Numeric Rating Scale for Breathlessness, ALSFRS-R respiratory subscale and Dyspnea-12, contributed by participants in the Trajectories of Outcome in Neurological Conditions-ALS study. Rasch analysis converts ordinal scale data to interval equivalents. Results: Data from 1120 people with ALS showed ALSFRS-R Respiratory is only valid as ordinal data. The NRS Breathlessness requires computation from a wider NRS set for Rasch analysis; its SDD is 3.2, MDC 2.59, MIC 2.39, with score range of 0-10. The Dyspnea-12 has SDD 7.0, MDC 6.14, MIC 4.5, with score range of 0-36. The %MDC, indicating smallest change detectable above measurement error as % of scale range, is superior for the Dyspnea-12 (17.1%) compared to the NRS Breathlessness (25.9%). Another advantage of Dyspnea-12 is transformation of raw ordinal to interval equivalent data using published conversion tables. Both NRS and Dyspnea-12 have disadvantages of MIC < MDC. Conclusions: Accurate measurement underpins optimal clinical decision making and high-quality research. Informed choice of PROMs reduces risk of misinterpreting clinical and research data. Patients want PROMs which they feel give an accurate account of their progression when participating in research and communicating with their clinical team. The Dyspnea-12 is preferrable for clinical and research use based on its psychometric properties.}, } @article {pmid40685330, year = {2025}, author = {Far, BF and Akbari, M and Habibi, MA and Katavand, M and Nasseri, S}, title = {CRISPR Technology in Disease Management: An Updated Review of Clinical Translation and Therapeutic Potential.}, journal = {Cell proliferation}, volume = {}, number = {}, pages = {e70099}, doi = {10.1111/cpr.70099}, pmid = {40685330}, issn = {1365-2184}, abstract = {CRISPR-Cas9 technology has rapidly advanced as a transformative genome-editing platform, facilitating precise genetic modifications and expanding therapeutic opportunities across various diseases. This review explores recent developments and clinical translations of CRISPR applications in oncology, genetic and neurological disorders, infectious diseases, immunotherapy, diagnostics, and epigenome editing. CRISPR has notably progressed in oncology, where it enables the identification of novel cancer drivers, elucidation of resistance mechanisms, and improvement of immunotherapies through engineered T cells, including PD-1 knockout CAR-T cells. Clinical trials employing CRISPR-edited cells are demonstrating promising results in hematologic malignancies and solid tumours. In genetic disorders, such as hemoglobinopathies and muscular dystrophies, CRISPR-Cas9 alongside advanced editors like base and prime editors show significant potential for correcting pathogenic mutations. This potential was affirmed with the FDA's first approval of a CRISPR-based therapy, Casgevy, for sickle cell disease in 2023. Neurological disorders, including Alzheimer's, ALS, and Huntington's disease, are increasingly targeted by CRISPR approaches for disease modelling and potential therapeutic intervention. In infectious diseases, CRISPR-based diagnostics such as SHERLOCK and DETECTR provide rapid, sensitive nucleic acid detection, particularly valuable in pathogen outbreaks like SARS-CoV-2. Therapeutically, CRISPR systems target viral and bacterial genomes, offering novel treatment modalities. Additionally, CRISPR-mediated epigenome editing enables precise regulation of gene expression, expanding therapeutic possibilities. Despite these advances, significant challenges remain, including off-target effects, delivery methodologies, immune responses, and long-term genomic safety concerns. Future improvements in editor precision, innovative delivery platforms, and enhanced safety assessments will be essential to fully integrate CRISPR-based interventions into standard clinical practice, significantly advancing personalised medicine.}, } @article {pmid40684954, year = {2025}, author = {Zheng, B and Du, S and Wei, M and Xia, W and Jiang, Y and Zhou, J and Zhang, J}, title = {Association of allostatic load and dietary inflammatory index with depressive symptoms among U.S. adults: NHANES 2007-2018.}, journal = {Journal of affective disorders}, volume = {391}, number = {}, pages = {119955}, doi = {10.1016/j.jad.2025.119955}, pmid = {40684954}, issn = {1573-2517}, abstract = {BACKGROUND: Both chronic stress and pro-inflammatory diets have been independently linked to depressive symptoms (DSs). However, their joint effects are uncertain.

METHODS: This study included 20,446 U.S. adults from the National Health and Nutrition Examination Survey (NHANES) 2007-2018. Chronic stress was quantified using allostatic load score (ALS) derived from eight biomarkers. Dietary inflammatory potential was quantified using Dietary Inflammation Index (DII) calculated from two 24-h dietary recalls. DSs were assessed using the Patient Health Questionnaire-9 (PHQ-9). Weighted logistic regression, restricted cubic splines (RCS), mediation, and population attributable fraction (PAF) analyses were conducted.

RESULTS: Both ALS (adjusted odds ratio [aOR] = 1.23, 95 % confidence interval [CI]: 1.16-1.29) and DII (aOR = 1.21, 95%CI:1.15-1.26) independently and synergistically increased DSs risk, showing significant linear trends (both P-overall<0.001) with no evidence of nonlinearity. The highest-risk group (highest ALS quartile + pro-inflammatory diet) exhibited a 3.94-fold increased risk (aOR = 4.94, 95 % CI: 2.73-8.94) compared to the reference group. DII partially mediated the ALS-DSs association (mediation proportion: 4.27 %, 95 % CI: 2.96 %-6.00 %). Eliminating high ALS and pro-inflammatory diets could prevent 40.4 % (95 % CI: 31.7-49.2 %) of depression cases.

LIMITATIONS: The cross-sectional design limits causal inference, and residual confounding may exist due to unmeasured factors.

CONCLUSIONS: This study highlights the independent, synergistic, and mediated effects of ALS and DII on DSs. Integrated interventions addressing both stress and diet may help mitigate depression burden in U.S. adult.}, } @article {pmid40684811, year = {2025}, author = {Debernard, S and Aguilar, P and Maria, A and Fuentes, A and Couzi, P and Bozzolan, F and Gassias, E and Force, E}, title = {Endocrine responses in the pheromone induction of male sexual maturation in an insect.}, journal = {Insect biochemistry and molecular biology}, volume = {183}, number = {}, pages = {104365}, doi = {10.1016/j.ibmb.2025.104365}, pmid = {40684811}, issn = {1879-0240}, abstract = {In animals, sexual maturation is marked by the development of reproductive behaviors in synchronism with the acquisition of fertility, and this timing is influenced by chemosensory experiences. In naïve and immature individuals, exposure to sex pheromones may accelerate sexual development, and mechanisms underlying this pheromone induction are not fully identified. Using the moth Agrotis ipsilon, we showed that pre-exposure of immature males to female sex pheromones led to early increases in the performance of sex pheromone-triggered oriented flight as well as in the maturation of accessory sex glands (ASGs) producing seminal proteins. Conjointly, biosynthesis and circulating amounts of juvenile hormone (JH) raised with an upregulation of the expression of JH receptor, Methoprene-tolerant 1 (Met1) and the JH-inducible transcription factor, Krüppel homolog 1 (Kr-h1) in ASGs and the primary olfactory centers, the antennal lobes (ALs). In the sex pheromone pre-exposed immature males, the loss of function of Met1 or Kr-h1 caused a reduction in the induction of the sex pheromone behavioral responsiveness and the ASG secretory activity. Taken together, our results showed that the accelerated effects of sex pheromone pre-exposure on male sexual maturation are mediated by increased JH biosynthesis. This ultimately leads to early induction of JH signaling in ASGs for seminal protein production and in ALs for the central processing of pheromone information, which causes the display of sexual behavior in male A. ipsilon. Finally, this study expands our understanding of endocrine mechanisms by which animals can modulate their fitness according to past olfactory experiences.}, } @article {pmid40684739, year = {2025}, author = {Rudell, EC and Cutti, L and Turra, GM and Angonese, PS and Tasca, VF and Dos Santos, OD and Patterson, E and Merotto, A}, title = {Variability and spatial distribution of ALS-inhibitor resistance mechanisms in Brazilian Echinochloa crus-galli.}, journal = {Plant physiology and biochemistry : PPB}, volume = {228}, number = {}, pages = {110237}, doi = {10.1016/j.plaphy.2025.110237}, pmid = {40684739}, issn = {1873-2690}, abstract = {Barnyardgrass (Echinochloa crus-galli (L.) P. Beauv.) is a hexaploid weed, commonly found in rice fields. The field-level frequencies of the herbicide resistance mechanisms present in barnyardgrass remain unknown. This study developed and compared molecular marker assays for detecting mutations in the ALS genes, analyzing their frequency and spatial distribution in Southern Brazil rice fields. The ALS gene of 52 accessions was sequenced to identify mutations associated with resistance. Single Nucleotide-Amplified Polymorphism (SNAP) and PCR Allele Competitive Extension (PACE®) markers were developed for detecting ALS mutations: A122T, A205N, W574L, and S653N. A total of 233 accessions that survived imidazolinone application were collected. A greenhouse assay identified 195 and 84 accessions resistant to imazapyr + imazapic and penoxsulam, respectively. Molecular assays detected 188 resistant accessions, with W574L, S653N, A122T, and A205N mutations present in 43 %, 29 %, 17 %, and 5 % of resistant samples, respectively. 6 % of accessions carried mutations in two positions, while six resistant accessions lacked any mutation. Efficiency of SNAP and PACE methods was 90 % and 82 %, respectively. Discrepancies between methods were resolved using Nanopore sequencing. The detection threshold was one resistant per 25 susceptible DNA samples and one per 10 using leaf discs in SNAP. All mutations were distributed geographically, with the frequency of W574L increasing from 40 % in 2017/2018 to 47 % in the 2022/2023 season. ALS resistance was detected in 80 % of the accessions. Epidemiological studies, like this, that track resistance mechanisms, including the occurrence, distribution, and variability of mutations, are crucial for improving weed control recommendations.}, } @article {pmid40683959, year = {2025}, author = {Khera, P and Kumar, A and Kapila, R}, title = {Decision tree for severity assessment of neurodegenerative diseases using possibility approach and gait dynamics.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {26247}, pmid = {40683959}, issn = {2045-2322}, mesh = {Humans ; Severity of Illness Index ; Male ; *Neurodegenerative Diseases/diagnosis/physiopathology ; Female ; *Decision Trees ; *Gait/physiology ; Middle Aged ; Aged ; Parkinson Disease/physiopathology/diagnosis ; Huntington Disease/physiopathology/diagnosis ; Amyotrophic Lateral Sclerosis/physiopathology/diagnosis ; Adult ; *Gait Analysis/methods ; }, abstract = {Accurate and timely diagnosis of neurodegenerative disease (NDD) severity is crucial for clinical needs. Existing assessment methods for grading disease severity are mostly dependent on movement disorder specialist opinion resulting in subjectivity and inherent limitations. Gait instrumentation, on the other hand, can be used as a reliable tool to record various contrasting primary gait features. However, these features are agonized by individual's physical dimensions causing data dispersion. This study proposes normalized feature set, and a decision tree (DT) based model to evaluate NDD severity. The study investigates the use of raw sensor signals from foot resistive switches (FSR) to determine high-level gait features for detection of disease severity in patients suffering from neurodegenerative disorders. The methodology includes three-step DT-based approach. First, NDD patients were classified from healthy controls (HC). Disorders were categorized into Parkinson's disease (PD), Amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD). Finally, disease severity was determined on clinical scale. Experimental results were established using 11,084 gait pattern recordings from NDD patients and HC. The proposed framework achieved a high coefficient of determination (R[2] ≈ 0.90) and low error rates with stratified 10-fold cross-validation. Comparatively, it outperformed conventional DT models. Statistical validation via the Wilcoxon signed-rank test confirmed the significance of the finding. The proposed computer aided gait analysis framework demonstrated high accuracy and reliability in diagnosing NDD severity. The accuracy and reliability of proposed framework for disease severity diagnosis is crucial for dose management and to determine the disease progress rate in NDD patients.}, } @article {pmid40683546, year = {2025}, author = {Mehboodi, M and Namdari, MP and Abdollahi, Z and Mobarezi, Z and Kiani, M and Chamani, F and Khanbabaie, H and Rabiei, S and Maleki, MH and Sanati, H and Shahedin, GJ and Isaei, E}, title = {The relationship between increased levels of microbiota-derived lipopolysaccharide in obesity and the pathophysiology of neurodegenerative diseases.}, journal = {Microbial pathogenesis}, volume = {207}, number = {}, pages = {107905}, doi = {10.1016/j.micpath.2025.107905}, pmid = {40683546}, issn = {1096-1208}, mesh = {Humans ; *Lipopolysaccharides/metabolism ; *Obesity/microbiology/complications ; *Neurodegenerative Diseases/physiopathology/microbiology/etiology ; *Gastrointestinal Microbiome/physiology ; Animals ; Inflammation ; Blood-Brain Barrier ; Oxidative Stress ; }, abstract = {Lipopolysaccharide (LPS), a potent pro-inflammatory endotoxin derived from the outer membrane of Gram-negative bacteria, has been identified as a crucial link between obesity-related systemic inflammation and the onset of neurodegenerative diseases. Modifications in gut microbiota associated with obesity disrupt the integrity of the intestinal barrier, resulting in increased permeability and heightened levels of circulating LPS a phenomenon known as metabolic endotoxemia. The elevated presence of LPS promotes persistent low-grade inflammation and oxidative stress, both of which are critical contributors to neurodegeneration. This review aims to explore the biological pathways through which LPS influences the development and advancement of neurodegenerative diseases, including Parkinson's disease (PD), Alzheimer's disease (AD), multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS). The role of LPS in exacerbating neuroinflammation through the activation of microglia and the impairment of the blood-brain barrier (BBB) is thoroughly examined. Moreover, the review delves into the interrelated effects of obesity-related systemic inflammation, insulin resistance, and mitochondrial dysfunction in enhancing LPS-driven neurodegenerative mechanisms. Special emphasis is placed on the common pathological characteristics present in these disorders, such as protein misfolding, neuronal apoptosis, and disrupted synaptic function, which may be exacerbated by LPS-related processes. By clarifying the relationships between obesity, LPS, and neurodegenerative diseases, this review underscores potential therapeutic approaches aimed at modulating gut microbiota, improving intestinal barrier function, and mitigating systemic inflammation to prevent or decelerate the progression of these debilitating disorders.}, } @article {pmid40683276, year = {2025}, author = {Harkness, JR and McDermott, JH and Marsden, S and Jamieson, P and Metcalfe, KA and Khan, N and Macken, WL and Pitceathly, RDS and Record, CJ and Maroofian, R and Kleopa, K and Christodoulou, K and Sabir, A and Islam, L and Santra, S and Durmusalioglu, EA and Atik, T and Isik, E and Cogulu, O and Urquhart, JE and Beaman, GM and Demain, LA and Jackson, A and Blakes, AJM and Byers, HJ and Bennett, H and Lin, WH and Adamson, A and Patel, S and Yue, WW and Taylor, RW and Reunert, J and Marquardt, T and Buchert, R and Haack, T and Losch, H and Ryba, L and Lassuthova, P and Valkovičová, R and Haberlová, J and Lauerová, B and Trúsiková, E and Polavarapu, K and Kilicarslan, OA and Lochmüller, H and Zamani, M and Chamanrou, N and Shariati, G and Sadeghian, S and Azizimalamiri, R and Maddirevula, S and AlMuhaizea, M and Alkuraya, FS and Horvath, R and Gungor, S and Manzur, A and Munot, P and Matthews, R and Banka, S and Reilly, MM and Bennett, D and O'Keefe, RT and Newman, WG}, title = {Acute-onset axonal neuropathy following infection in children with biallelic RCC1 variants: a case series.}, journal = {The Lancet. Neurology}, volume = {24}, number = {8}, pages = {667-680}, doi = {10.1016/S1474-4422(25)00198-X}, pmid = {40683276}, issn = {1474-4465}, mesh = {Adolescent ; Animals ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Male ; *Cell Cycle Proteins/genetics ; *Infections/complications ; *Peripheral Nervous System Diseases/etiology ; Drosophila ; Nuclear Proteins ; Guanine Nucleotide Exchange Factors ; }, abstract = {BACKGROUND: The reasons why some individuals have severe neuropathy following an infection are not known. Through the agnostic screening of children with acute axonal neuropathy after an infection, we identified several families with biallelic variants in RCC1. We aimed to describe the clinical phenotype of these patients, and the molecular and cellular pathology associated with the genetic variants identified in these families.

METHODS: For this case series, we identified children affected by a severe, acute-onset axonal neuropathy following infection through an international research consortium of paediatric neurologists and clinical geneticists from nine countries (Canada, Cyprus, Czechia, Germany, Iran, Saudi Arabia, Slovakia, Türkiye, and the UK). Clinical assessments included nerve conduction studies and neuroimaging. We did exome or genome sequencing in DNA samples from all patients. We characterised the proteins encoded by the genetic variants by use of thermal stability and enzymatic assays, using recombinantly expressed proteins. We assessed cellular protein transport under heat or oxidative stress by use of immunofluorescence in primary fibroblasts, obtained from patients. We generated a humanised Drosophila knock-in model to assess the effects of stress on the in vivo function of RCC1.

FINDINGS: Between Nov 2, 2011, and July 10, 2024, we identified 24 individuals from 12 families who had severe, acute-onset axonal neuropathy following infection (13 female and 11 male patients, with a mean age at diagnosis of 1 year 10 months [SD 2·27]). Eight biallelic missense variants in RCC1 were identified in affected individuals with autosomal recessive inheritance. Patients had variable phenotypes, ranging from rapidly progressive fatal axonal neuropathy to mild motor neuropathy with impaired walking. Neurological presentation was often secondary to an infection, resulting in initial misdiagnoses of Guillain-Barré syndrome in several patients. 15 children had disease recurrence. The disease was fatal in 15 patients. The RCC1 variants in these patients code for proteins that alter GDP-to-GTP exchange activity and have reduced thermal stability in vitro. In primary fibroblasts, heat shock or oxidative stress revealed defects in Ran nuclear localisation and impaired nucleocytoplasmic transport. A Drosophila model of the disease revealed a fatal intolerance to oxidative stress.

INTERPRETATION: We describe an autosomal recessive, acute-onset paediatric axonal neuropathy, seemingly triggered by infection, that affects individuals with biallelic RCC1 variants. In these children, the disease can mimic Guillain-Barré syndrome. The pathological mechanisms underlying this novel axonal neuropathy might overlap with those of amyotrophic lateral sclerosis. Cellular studies indicate that RCC1 variants affect nucleocytoplasmic transport, which is crucial for healthy axonal function. Future studies should be directed at pre-symptomatic treatment by exploring ways to maintain nucleocytoplasmic transport.

FUNDING: National Institute for Health and Care Research, LifeArc, and Wellcome Trust.}, } @article {pmid40682810, year = {2025}, author = {Gao, J and Douglas, AGL and Chalitsios, CV and Scaber, J and Talbot, K and Turner, MR and Thompson, AG}, title = {Neurodegenerative disease in C9orf72 repeat expansion carriers: population risk and effect of UNC13A.}, journal = {Brain : a journal of neurology}, volume = {}, number = {}, pages = {}, doi = {10.1093/brain/awaf269}, pmid = {40682810}, issn = {1460-2156}, abstract = {The C9orf72 hexanucleotide repeat expansion (HRE) is the most common monogenetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Neurodegenerative disease incidence in C9orf72 HRE carriers has been studied using cohorts from disease-affected families or by extrapolating from population disease incidence, potentially introducing bias. Age-specific cumulative incidence of ALS and dementia was estimated using Kaplan-Meier and competing risk models in C9orf72 HRE carriers compared to matched controls in UK Biobank. Risk modification by UNC13A genotype was examined. Of 490,331 individuals with valid genetic data, 701 had >100 repeats in C9orf72 (median age 55 [IQR 48-62], follow-up 13.4 years [12.3-14.1]). The cumulative incidence of ALS or dementia was 66% [95% CI 57-73%] by age 80 in C9orf72 HRE carriers versus 5.8% [4.5-7.0%] in controls, or 58% [50-64%] versus 5.1% [4.1-6.4%] accounting for the competing risk of other-cause mortality. Forty-one percent of dementia incidence accrued between age 75-80. C-allele homozygosity at rs12608932 in UNC13A increased ALS or dementia risk in C9orf72 HRE carriers (hazard ratio 1.81 [1.18 - 2.78]). C9orf72 HRE disease was incompletely penetrant in this population-based cohort, with risk modified by UNC13A genotype. This has implications for counselling at-risk individuals and modelling expected phenoconversion for prevention trials.}, } @article {pmid40682794, year = {2025}, author = {Sheikh Saleh, D and Mraer, L and Fatima, H and Gubari, H and Alsayed, MA and Hassan, FE}, title = {Decoding the Dialogue: Immunity and central nervous system interactions in neurodegenerative diseases.}, journal = {The Egyptian journal of immunology}, volume = {32}, number = {3}, pages = {20-31}, doi = {10.55133/eji.320303}, pmid = {40682794}, issn = {1110-4902}, mesh = {Humans ; *Neurodegenerative Diseases/immunology ; *Central Nervous System/immunology ; Animals ; Immunity, Innate ; *Neuroimmunomodulation ; Microglia/immunology ; Astrocytes/immunology ; Blood-Brain Barrier/immunology ; }, abstract = {This review article aims to discuss neuroimmune interactions by emphasizing the role of central and peripheral immunities in central nervous system (CNS) protection and function, as well as how abnormalities in this relationship may be implicated in the genesis of neurodegenerative diseases (NDDs). Immune elements that play roles within the CNS both during stable and infectious states are described. Innate CNS immunity is explored as a distinct entity comprised of the brain blood barrier, CNS parenchyma, and resident immune cells-microglia and astrocytes, whose roles in antigen recognition and clearance and neuromodulation are further enumerated. Due to the inability of the CNS to independently initiate an adaptive immune response, the necessary recruitment and regulation of elements from the peripheral immune system (PIS) are described in a process that, in chief, utilizes resident antigen-presenting cells to prime naïve T-cells, which later enter the CNS through areas of access to the cerebrospinal fluid. The previous modes of interaction especially enable microglia, astrocytes, and T-cells to play part in neurodevelopment and plasticity, and the proposed mechanisms by which they participate in synaptic pruning, neurogenesis, and memory are examined. In addition to its protective role, the PIS has also been shown to play a regulatory role in the CNS, where it drives responses that optimize immune function, such as fever and sickness behavior. Due to the high level of involvement of the immune system within the CNS, dysregulations of the immune system are thought to be implicated in numerous NDD pathogeneses, where neuroinflammation both causes and is caused by immune reactions. Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis are particularly discussed.}, } @article {pmid40682648, year = {2025}, author = {Belosludtseva, NV and Mikheeva, IB and Starinets, VS and Dubinin, MV and Belosludtsev, KN}, title = {Age-Dependent Changes in Mitochondrial Regulatory Mechanisms in the Spinal Cord of SOD1-G93A-Transgenic Mice with the Phenotype of Amyotrophic Lateral Sclerosis.}, journal = {Bulletin of experimental biology and medicine}, volume = {179}, number = {1}, pages = {34-40}, pmid = {40682648}, issn = {1573-8221}, mesh = {Animals ; *Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology ; Mice, Transgenic ; *Mitochondria/metabolism/genetics/ultrastructure/pathology ; Mice ; *Spinal Cord/metabolism/pathology/ultrastructure ; *Superoxide Dismutase-1/genetics/metabolism ; Motor Neurons/metabolism/pathology/ultrastructure ; Ubiquitin-Protein Ligases/genetics/metabolism ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/genetics/metabolism ; Protein Kinases/genetics/metabolism ; Mice, Inbred C57BL ; Disease Models, Animal ; GTP Phosphohydrolases/genetics/metabolism ; Dynamins/genetics/metabolism ; Phenotype ; Mitochondrial Dynamics/genetics ; Mitochondrial Proteins/genetics/metabolism ; Superoxide Dismutase/genetics/metabolism ; Humans ; Male ; Mitophagy ; NF-E2-Related Factor 2 ; }, abstract = {Age-dependent changes in the expression level of genes encoding proteins responsible for mitochondrial homeostasis were studied in relation to ultrastructural abnormalities in the mitochondria of motor neurons in the anterior horns of the spinal cord in a transgenic model of amyotrophic lateral sclerosis (SOD1-G93A mice). The expression of the Drp1, Mfn2, Ppargc1a, and Nefl genes was reduced, and the expression of the Nfe2l2, Pink1, and Parkin genes was enhanced in mice with the genotype of the familial form of the disease at the age of 22 weeks corresponding to the symptomatic stage in comparison with wild-type mice (C57BL6 × SJL) and non-transgenic littermates (SOD1-G93A(Tg-)) of the same age. Comparative analysis of spinal cord tissue samples from 8 and 12 weeks-old animals revealed no significant differences in the expression levels of genes encoding proteins responsible for mitochondrial dynamics, biogenesis, and mitophagy. Electron microscopic examination showed pronounced structural alterations in mitochondria in the soma of lower motor neurons of SOD1-G93A(Tg+) mice at the symptomatic stage, which manifested in the appearance of "ring-like" mitochondrial structures, matrix swelling, destruction of membranes in the cristae, and increased number of autophagolysosomes. The role of mitochondrial homeostasis disorders in the progression of amyotrophic lateral sclerosis is discussed.}, } @article {pmid40681694, year = {2025}, author = {Muqaku, B and Dorst, J and Wiesenfarth, M and Otto, M and Ludolph, AC and Oeckl, P}, title = {Peptidomic analysis of CSF reveals new biomarker candidates for amyotrophic lateral sclerosis.}, journal = {EMBO molecular medicine}, volume = {17}, number = {8}, pages = {1926-1949}, pmid = {40681694}, issn = {1757-4684}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/cerebrospinal fluid/pathology ; *Biomarkers/cerebrospinal fluid ; Female ; Male ; Middle Aged ; Aged ; *Peptides/cerebrospinal fluid ; Cohort Studies ; Mass Spectrometry ; Proteomics/methods ; Adult ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease, and novel biomarkers are needed. We applied mass-spectrometry-based peptidomic analysis in cerebrospinal fluid (CSF) samples of ALS and non-neurodegenerative control patients (Con) from a discovery (n = 48) and validation (n = 109) cohort for biomarker discovery. Systematic selection revealed a panel of eight novel peptide biomarker candidates for ALS (out of 33,605) derived from seven proteins. In the validation cohort, NFL, MAP1B, MYL1, and APOC1 peptides were upregulated, and peptides from CADM3, SCG1, and PENK were downregulated in ALS compared to Con. The peptides (except NFL) were not changed in other neurodegenerative diseases, including Alzheimer´s disease, frontotemporal dementia and Parkinson´s disease. Combination of all peptides in a logistic regression model led to an area under the curve value of 98% for the discrimination of ALS from controls. Data of the NFL peptide strongly correlated with an established NFL immunoassay (Ella, r = 0.97). The peptide biomarker candidates are derived from proteins with different function, and their determination with our method provides the opportunity for simultaneous investigation of key processes in ALS.}, } @article {pmid40681220, year = {2025}, author = {Abd El-Aziz, MK and Wadan, AS and Albahttiti, ATI and Moradikor, N}, title = {Emotional stress and cardiovascular health: Impacts on neurodegenerative disease progression.}, journal = {Progress in brain research}, volume = {294}, number = {}, pages = {101-133}, doi = {10.1016/bs.pbr.2025.04.004}, pmid = {40681220}, issn = {1875-7855}, mesh = {Humans ; *Stress, Psychological/physiopathology/complications/metabolism ; *Neurodegenerative Diseases/physiopathology/metabolism ; *Cardiovascular Diseases/physiopathology/metabolism ; Disease Progression ; Hypothalamo-Hypophyseal System/physiopathology/metabolism ; Pituitary-Adrenal System/physiopathology/metabolism ; }, abstract = {Stress is an inevitable part of people's lives and is considered to have a severe impact on health, especially in the case of cardiovascular diseases and neurodegenerative diseases. This chapter aims to reveal the links between emotional stress, cardiovascular health, and neurodegenerative disease progression. Chronic stress is therefore recognized as a significant cause of cardiovascular diseases mainly because of the effects it has on the hypothalamic-pituitary-adrenal (HPA) axis and the (SNS) sympathetic which neurodegenerative nervous are diseases system such (as ALS) through inflammation of Alzheimer's mechanisms and disease, vascular such as Parkinson's functions. The mechanisms of work also establish the crosstalk between CVD and NDD, demonstrating that they share genetic, molecular, and systemic associations. It is essential to know these pathways to design interventions that will help prevent or lessen the effects of stress on health and thus enhance patient care.}, } @article {pmid40680640, year = {2025}, author = {Vucic, S}, title = {Gamma activation in Amyotrophic lateral sclerosis: Support for the interneuronal dysfunction theory.}, journal = {Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology}, volume = {177}, number = {}, pages = {2110827}, doi = {10.1016/j.clinph.2025.2110827}, pmid = {40680640}, issn = {1872-8952}, } @article {pmid40680585, year = {2025}, author = {Osoba, HO}, title = {Commentary on 'Retinal Alterations Induced by Amyotrophic Lateral Scerosis: an Analysis Using Optical Coherence Tomography': Drawing Out the Ramifications.}, journal = {Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia}, volume = {140}, number = {}, pages = {111514}, doi = {10.1016/j.jocn.2025.111514}, pmid = {40680585}, issn = {1532-2653}, } @article {pmid40679526, year = {2025}, author = {Khairullin, AE and Efimova, DV and Teplov, AY and Khabibrakhmanov, AN and Nagiev, KK and Grishin, SN and Ziganshin, AU and Mukhamedyarov, MA}, title = {Impairment of P2 Receptor-Mediated Modulation of Skeletal Muscle Contractions in Transgenic Mice with Modeled Amyotrophic Lateral Sclerosis.}, journal = {Bulletin of experimental biology and medicine}, volume = {179}, number = {1}, pages = {20-23}, pmid = {40679526}, issn = {1573-8221}, mesh = {Animals ; *Amyotrophic Lateral Sclerosis/physiopathology/metabolism/genetics ; Mice, Transgenic ; Mice ; *Muscle Contraction/drug effects/physiology ; *Muscle, Skeletal/drug effects/metabolism/physiopathology ; Disease Models, Animal ; Adenosine Triphosphate/pharmacology ; *Receptors, Purinergic P2/metabolism/genetics ; RNA-Binding Protein FUS/genetics/metabolism ; Diaphragm/drug effects/physiopathology/metabolism ; Male ; }, abstract = {We studied the effects of ATP on skeletal muscle contractility in FUS-transgenic mice with amyotrophic lateral sclerosis (ALS) model. Mechanomyography showed that ATP application did not increase the amplitude of electrically induced contractions of the diaphragm muscle, m. extensor digitorum longus, and soleus muscle in FUS-transgenic mice unlike wild-type mice. Application of a non-selective P2 receptor antagonist suramine and application of ATP against the background of suramine did not change the amplitude of contractions of the studied skeletal muscles in FUS-transgenic mice. Thus, FUS model of ALS is based on the impairment of purinergic regulation of skeletal muscle contractile activity, which can play a role in the pathogenesis of ALS.}, } @article {pmid40678914, year = {2025}, author = {Calma, AD and Pavey, N and Silva, CS and Tsuji, Y and Van den Bos, MAJ and Farrar, MA and Menon, P and Vucic, S}, title = {Clinical Utility of Far-Field Potentials in Amyotrophic Lateral Sclerosis.}, journal = {Muscle & nerve}, volume = {}, number = {}, pages = {}, doi = {10.1002/mus.28480}, pmid = {40678914}, issn = {1097-4598}, abstract = {INTRODUCTION/AIMS: Far field potentials (FFP) have been proposed as a reliable neurophysiological prognostic biomarker in amyotrophic lateral sclerosis (ALS). This study evaluates the diagnostic utility of ulnar nerve FFP in ALS.

METHODS: Comprehensive peripheral neurophysiological assessments were conducted in 62 ALS and 43 ALS-mimicking disorder participants. The ulnar nerve was stimulated at the wrist, recording motor responses over the abductor digit minimi (ADM) muscle. Conventional compound muscle action potentials (CMAP), FFP, and near field potential amplitudes were recorded, alongside the split-hand index, neurophysiological index, motor unit number estimation (MScanFit-MUNE), and motor unit index (MUNIX). Diagnostic utility was evaluated using receiver operating characteristic (ROC) analysis.

RESULTS: In ALS, FFP amplitude was significantly lower (5.07 ± 0.36 mV) compared to ALS mimics (8.25 ± 0.40 mV, p < 0.001). FFP amplitude exhibited a moderate-to-strong correlation with neurophysiological biomarkers, including CMAP amplitude (ρ = 0.77, p < 0.001), split-hand index (ρ = 0.53, p < 0.001), neurophysiological index (ρ = 0.52, p < 0.001), MUNIX (ρ = 0.69, p < 0.001), and MScanFit-MUNE (ρ = 0.66, p < 0.001). Weak-to-moderate correlations were also observed with clinical measures of disease progression, including upper limb muscle strength, ALS functional rating score-revised (ALSFRS-R) and the rate of decline in the ALSFRS-R fine motor subscore. ROC analysis demonstrated that FFP amplitude reliably distinguished ALS from mimicking disorders (AUC = 0.80, 95% CI: 0.71-0.89), with consistent diagnostic accuracy across ALS phenotypes.

DISCUSSION: The diagnostic capability of FFP amplitude was comparable to established neurophysiological biomarkers utilized in ALS. It is a promising prognostic and diagnostic biomarker for ALS. Its simplicity and reproducibility complement traditional neurophysiological measures, offering potential for clinical application in ALS diagnosis and monitoring.}, } @article {pmid40675818, year = {2025}, author = {Mei, I and Nichterwitz, S and Leboeuf, M and Nijssen, J and Lenoel, I and Repsilber, D and Lobsiger, CS and Hedlund, E}, title = {Transcriptional modulation unique to vulnerable motor neurons predicts ALS across species and SOD1 mutations.}, journal = {Genome research}, volume = {}, number = {}, pages = {}, doi = {10.1101/gr.279501.124}, pmid = {40675818}, issn = {1549-5469}, abstract = {Amyotrophic lateral sclerosis (ALS) is characterized by the progressive loss of motor neurons (MNs) that innervate skeletal muscles. However, certain MN groups including ocular MNs, are relatively resilient. To reveal key drivers of resilience versus vulnerability in ALS, we investigate the transcriptional dynamics of four distinct MN populations in SOD1G93A ALS mice using LCM-seq and single molecule fluorescent in situ hybridization. We find that resilient ocular MNs regulate few genes in response to disease. Instead, they exhibit high baseline gene expression of neuroprotective factors including En1, Pvalb, Cd63 and Gal, some of which vulnerable MNs upregulate during disease. Vulnerable motor neuron groups upregulate both detrimental and regenerative responses to ALS and share pathway activation, indicating that breakdown occurs through similar mechanisms across vulnerable neurons, albeit with distinct timing. Meta-analysis across four rodent mutant SOD1 MN transcriptome datasets identify a shared vulnerability code of 39 genes including Atf4, Nupr1, Ddit3, and Penk, involved in apoptosis as well as proregenerative and anti-apoptotic signature consisting of Atf3, Vgf, Ina, Sprr1a, Fgf21, Gap43, Adcyap1, and Mt1 Machine learning using genes upregulated in SOD1G93A spinal MN predicts disease in human stem cell-derived SOD1E100G MNs, and shows that dysregulation of VGF, INA, and PENK are strong disease-predictors across species and SOD1 mutations. Our study reveals MN population-specific gene expression and temporal disease-induced regulation that together provide a basis to explain ALS selective vulnerability and resilience and that can be used to predict disease.}, } @article {pmid40675338, year = {2025}, author = {Shtilbans, A}, title = {Combination Supplement Therapy: A New Frontier in Treatment of Neurodegenerative Diseases.}, journal = {The Journal of nutrition}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.tjnut.2025.07.004}, pmid = {40675338}, issn = {1541-6100}, abstract = {This review highlights the importance and potential beneficial effects of dietary supplements, including taurine, tauroursodeoxycholic acid (TUDCA), curcumin, coenzyme Q10, creatine, and N-acetylcysteine, in the management of neurodegenerative diseases. Studies in preclinical models have consistently shown significant potential of these supplements in mitigating neurodegenerative pathology. Through a range of mechanisms targeting different molecular pathways, these supplements demonstrate therapeutic outcomes in preclinical models of conditions such as Parkinson disease, Alzheimer disease, amyotrophic lateral sclerosis, and Huntington disease. This review discusses published data on each of these supplements in the context of neurodegenerative diseases. It also discusses a combination therapy concept and proposes a strategy to formulate an optimal blend of these supplements. This combination approach will target key processes, including mitochondrial dysfunction, protein misfolding, neuroinflammation, and oxidative stress responsible for neurodegenerative conditions. Additionally, this review examines various models used for both the initial screening and subsequent assessment of candidate supplement combinations.}, } @article {pmid40673975, year = {2025}, author = {Giorgi, A and Heckman, CJ and Perreault, MC}, title = {Spinally Projecting Serotonergic Neurons in Motor Network Modulation.}, journal = {Journal of neurophysiology}, volume = {}, number = {}, pages = {}, doi = {10.1152/jn.00139.2025}, pmid = {40673975}, issn = {1522-1598}, support = {20153//National Science Foundation (NSF)/ ; }, abstract = {Spinally projecting serotonergic (5-HTsp) neurons represent a heterogeneous population of neurons in the brainstem whose relevance in the control of movement has largely been inferred. Numerous studies across a variety of species have suggested that 5-HTsp neurons exert a widespread influence on spinal sensorimotor networks, operating at multiple levels (primary afferents, interneurons, and motoneurons) through various serotonin receptor subtypes. However, despite the anatomical and neurochemical complexity of the 5-HTsp system, most supporting evidence has largely been derived from indirect approaches (e.g., exogenous application of 5-HT and agonists/antagonists of 5-HT receptors). Direct demonstrations of specific anatomical and functional connectivity have been limited, occasionally yielding apparent discrepant results. Consequently, as the primary provider of serotonin to the spinal cord, the exact contributions of the 5-HTsp neurons remain to be fully elucidated. For this mini-review, we sifted through the literature of the last six decades, starting after the characterization of the brainstem raphe nuclei and monoaminergic systems [1-3], to provide a clearer picture of what is currently known of the anatomy and influences of the different populations of 5-HTsp neurons on sensorimotor circuits and motor behaviors. We focused on studies reporting direct manipulation of brainstem 5-HTsp neurons, excluding those targeting 5-HT neurotransmission by exogenous application of 5-HT. This emphasis aims to highlight the urgency of resolving how 5-HTsp neuron subpopulations differentiate anatomically and functionally, so that they can be integrated as dedicated components in current models of supraspinal control of movement and motor diseases such as Parkinson's and amyotrophic lateral sclerosis. Along the way, we point out gaps in knowledge that may be filled using newly available research tools.}, } @article {pmid40673945, year = {2025}, author = {Shan, D and Sun, X and Tang, Y and Zhao, Y and Yan, C and Liu, F}, title = {FUS protein nuclear loss in skin biopsy: A window into the pathology and diagnosis of fused in sarcoma-associated amyotrophic lateral sclerosis.}, journal = {Journal of neuropathology and experimental neurology}, volume = {}, number = {}, pages = {}, doi = {10.1093/jnen/nlaf077}, pmid = {40673945}, issn = {1554-6578}, support = {ZR2023MH180//Natural Science Foundation of Shandong Province/ ; 20201125//Qilu Young Scholar Program of Shandong University/ ; }, } @article {pmid40673755, year = {2025}, author = {Banerjee, A and Sanyal, D and Chattopadhyay, K}, title = {Investigating the Stability, Flexibility, and Phase Separation Properties of H46R and H80R Disease Mutants of SOD1: Insights into ALS Pathogenesis.}, journal = {Biochemistry}, volume = {64}, number = {15}, pages = {3358-3371}, doi = {10.1021/acs.biochem.5c00289}, pmid = {40673755}, issn = {1520-4995}, mesh = {*Amyotrophic Lateral Sclerosis/genetics/enzymology/pathology/metabolism ; *Superoxide Dismutase-1/genetics/chemistry/metabolism ; Humans ; Mutation ; Enzyme Stability ; Protein Stability ; Protein Structure, Secondary ; Protein Folding ; Molecular Dynamics Simulation ; Phase Separation ; }, abstract = {Human Cu, Zn superoxide dismutase (SOD1) is the primary enzyme in the cellular antioxidant defense system. Mutations in SOD1 are associated with amyotrophic lateral sclerosis (ALS), where protein misfolding and aggregation contribute to the disease pathology. Recently, SOD1 mutants have been shown to undergo phase separation, forming protein-rich droplets that can serve as precursors to the fibrillar aggregates, the pathological hallmarks of ALS. Protein phase separation is a critical process for membraneless organelle formation and the regulation of cellular activities, and its disruption is associated with neurodegeneration. In this study, we investigated two ALS-associated SOD1 mutants, H46R and H80R, and compared them to the wild-type (WT) and Apo forms to elucidate the relationship between phase separation and SOD1's biophysical properties. Using computational studies, chemical denaturation, in vitro condensate formation assays, and analyzing their dynamic behavior, we explored how these mutants influence protein phase separation propensity. Our findings demonstrate that altered secondary structures, stability, and inherent disorder in these mutants directly impact their phase separation behaviors. This study provides new insights into the role of phase separation in ALS pathogenesis and its potential as a therapeutic target.}, } @article {pmid40673749, year = {2025}, author = {Rong, P and Liston, E}, title = {An Explanatory Model of Speech Communication Centered on Multiscale Rhythmic Modulation: Implications for Motor Speech Assessment and Intervention for Individuals With Amyotrophic Lateral Sclerosis.}, journal = {Journal of speech, language, and hearing research : JSLHR}, volume = {68}, number = {7S}, pages = {3678-3702}, doi = {10.1044/2025_JSLHR-24-00286}, pmid = {40673749}, issn = {1558-9102}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology/complications ; Male ; Female ; Middle Aged ; Aged ; *Speech/physiology ; Speech Production Measurement/methods ; Cues ; Adult ; Phonetics ; *Speech Disorders/etiology/physiopathology ; Speech Acoustics ; Biomechanical Phenomena ; Periodicity ; }, abstract = {PURPOSE: This study proposed an explanatory model of speech communication centered on multiscale rhythmic modulation to inform motor speech assessment and management. To these ends, a fit-for-purpose, automated measurement tool was used to evaluate and/or cross-validate (a) the previously reported effect of a neuromotor disorder-amyotrophic lateral sclerosis (ALS)-and (b) the effects of two cueing strategies, commonly used in managing motor speech disorders, on rhythmic modulation of speech.

METHOD: A secondary analysis was carried out on the X-ray Microbeam database. The analyzed data included the articulatory-kinematic and acoustic recordings of a phonetically loaded sentence produced by 19 individuals with ALS and 23 neurologically healthy controls in one habitual style and two nonhabitual styles as elicited by the slow and clear speech cues, respectively. The measurement tool quantified the modulation patterns of four articulators as well as four critical-band and one wide-band envelopes at three linguistically relevant timescales (delta, theta, beta/gamma) to assess rhythm control at the prosodic, syllabic, and subsyllabic levels. To address the research aims, the disease and speaking style effects on all modulation metrics were evaluated.

RESULTS: For Aim 1, speakers with ALS showed reduced modulation depth of multiple articulators and critical-band envelopes at all timescales. For Aim 2, the slow speech cue elicited changes in articulatory modulation at multiple timescales, globally enhancing the control of all and especially syllabic and subsyllabic rhythms in speakers with ALS. Clear speech primarily elicited changes in articulatory modulation at the theta timescale, generating a more restricted effect on syllabic rhythm.

CONCLUSIONS: The findings generally aligned with our prior research, supporting the robust utility of the measurement tool for assessing rhythmic disturbances of speakers with ALS. Moreover, this tool showed promise for delineating cueing-elicited changes in rhythmic modulation of speech, which has potential implications in tailoring and evaluating the outcomes of behavioral intervention.}, } @article {pmid40673636, year = {2025}, author = {An, D and Wu, Y and Han, J and Fang, P and Bu, Y and Ji, G and Deng, J and Song, X}, title = {m6A Methylation-Induced Autophagy Impairment by TFEB Regulation in SOD1-G93A ALS Cell Model.}, journal = {American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics}, volume = {}, number = {}, pages = {e33048}, doi = {10.1002/ajmg.b.33048}, pmid = {40673636}, issn = {1552-485X}, support = {H2021206223//Natural Science Foundation of Hebei Province/ ; }, abstract = {We investigate the role of m6A RNA methylation in regulating transcription factor EB (TFEB) and its contribution to mitochondrial autophagy (mitophagy) dysfunction in amyotrophic lateral sclerosis (ALS). ALS cell models were used to analyse mitophagy markers and TFEB expression under METTL3 and TFEB modulation, using RT-qPCR, Western blot, MeRIP, RIP, and immunofluorescence. Elevated m6A methylation and reduced TFEB expression were observed in hSOD1-G93A models. METTL3 overexpression suppressed TFEB expression, leading to impaired mitophagy, while METTL3 knockdown alleviated these effects. MeRIP assays confirmed increased m6A modifications on TFEB mRNA, and RIP assays demonstrated direct interaction between METTL3 and TFEB mRNA. Notably, TFEB overexpression rescued mitophagy dysfunction, whereas TFEB knockdown exacerbated the impairment. METTL3-mediated m6A methylation inhibits mitophagy by downregulating TFEB expression, revealing the m6A-TFEB pathway as a promising therapeutic target for ALS.}, } @article {pmid40672339, year = {2025}, author = {Zeng, Y and Sianto, O and Lovchykova, A and Liu, C and Akiyama, T and Petrucelli, L and Gitler, AD}, title = {Nonsense-mediated decay masks cryptic splicing events caused by TDP-43 loss.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {40672339}, issn = {2692-8205}, support = {R35 NS097273/NS/NINDS NIH HHS/United States ; R35 NS137159/NS/NINDS NIH HHS/United States ; P01 NS084974/NS/NINDS NIH HHS/United States ; U54 NS123743/NS/NINDS NIH HHS/United States ; T32 AG047126/AG/NIA NIH HHS/United States ; R01 AG064690/AG/NIA NIH HHS/United States ; }, abstract = {In frontotemporal dementia and amyotrophic lateral sclerosis, the RNA-binding protein TDP-43 is lost from the nucleus, leading to cryptic exon inclusion events in dozens of neuronal genes. Here, we show that many cryptic splicing events have been missed by standard RNA-sequencing analyses because they are substrates for nonsense-mediated decay. By inhibiting nonsense-mediated decay in neurons we unmask hundreds of novel cryptic splicing events caused by TDP-43 depletion, providing a new picture to TDP-43 loss of function in neurons.}, } @article {pmid40672281, year = {2025}, author = {Hogan, AL and Kane, M and Chiu, P and Richter, G and Maurel, C and Wu, S and Scherer, NM and Don, EK and Lee, A and Blair, I and Chung, R and Morsch, M}, title = {Human TDP-43 overexpression in zebrafish motor neurons triggers MND-like phenotypes through gain-of-function mechanism.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2025.07.06.663393}, pmid = {40672281}, issn = {2692-8205}, abstract = {Dysregulation of the TAR DNA-binding protein 43 (TDP-43), including intraneuronal cytoplasmic mislocalisation and aggregation is a feature of multiple neurodegenerative diseases including amyotrophic lateral sclerosis (ALS), frontotemporal lobar dementia (FTLD), limbic-predominant age-related TDP-43 encephalopathy (LATE) and alzheimers disease (AD). Unravelling the causes and functional consequences of TDP-43 dysregulation is paramount to understanding disease mechanisms as well as identifying effective therapeutic targets. Here we present a comprehensive in vivo characterisation of three stable transgenic zebrafish models that express human TDP-43 variants in motor neurons. We demonstrate that overexpression of predominantly nuclear wildtype TDP-43, cytoplasm-targeted TDP-43, and an ALS-linked variant (G294V) each induce toxic gain-of-function effects, leading to impaired motor function, motor neuron loss, and muscle atrophy. Importantly, these models reveal distinct phenotypes, with the ALS-linked mutant exhibiting axonal transport deficits and neuromuscular junction disruption, while cytoplasmic mislocalised TDP-43 heightened susceptibility to oxidative stress. Two FDA-approved drugs used to treat ALS, edaravone and riluzole, were examined in these models and revealed that edaravone, but not riluzole, was effective in rescuing motor deficits associated with cytoplasmic TDP-43 expression and, to a lesser extent, mutant TDP-43 [G294V] . Collectively, these findings reveal distinct pathological consequences of TDP-43 dysregulation, providing neuron-centric mechanistic insights, and establish the humanised TDP-43 zebrafish as an efficient system for preclinical therapeutic testing.}, } @article {pmid40672164, year = {2025}, author = {Braspenning, SE and Ohnezeit, D and DeGulis, OA and Wilson, AC and Mohr, IJ}, title = {TDP-43 promotes efficient HSV-1 replication in human DRG-derived neurons.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2025.07.08.662712}, pmid = {40672164}, issn = {2692-8205}, abstract = {UNLABELLED: TAR DNA-binding protein 43 (TDP-43) is a versatile nuclear RNA-binding protein that performs important functions in RNA localization, processing and stability. In the neurodegenerative disease amyotrophic lateral sclerosis (ALS) TDP-43 forms toxic, insoluble cytoplasmic aggregates that ultimately lead to neuronal loss. Although TDP-43 is expressed in every cell type, its function and subcellular localization are particularly important for neuronal homeostasis. However, it is unknown if TDP-43 has a role during herpesvirus infection. Herpes simplex virus type-1 (HSV-1), a ubiquitous neurotropic pathogen, is considered a contributing factor to neurodegenerative disorders. In this study, we tested the requirement for TDP-43 during HSV-1 infection in neuronal and non-neuronal cells. HSV-1 infection of epithelial cells and primary fibroblasts did not change overall TDP-43 abundance, nor did TDP-43 depletion detectably alter HSV-1 replication in a multicycle growth experiment. By contrast, when TDP-43 was depleted in neuronally derived, matured HD10.6 cells, HSV-1 infectious virus production was significantly reduced in both single- and multicycle growth experiments. Notably, TDP-43 depletion restricts viral lytic gene expression at the immediate-early phase. Through nanopore direct RNA-sequencing we uncovered enhanced intron retention in two essential viral genes upon TDP-43 depletion. Thus, while depletion of TDP-43 does not affect replication in epithelial cells and fibroblasts, TDP-43 is required for efficient replication in HD10.6 cells through modifying the abundance and splicing of viral mRNAs.

IMPORTANCE: Herpes simplex virus type-1 is a widespread neurotropic pathogen that can cause life-threatening infections of the brain and is increasingly linked to neurodegenerative disease. However, due to the lack of scalable in vitro human neuronal models or small animal models that recapitulate disease, little is known about virus-host interactions in neurons specifically. Using human epithelial cells, primary fibroblasts and a human neuron-derived cell line, we uncovered a cell type specific TDP-43 requirement for efficient HSV-1 virus replication. TDP-43 is a critical neuronal disease gene, and we showed it promotes virus gene expression and splicing of viral mRNAs in neuron-derived cells. This work provides valuable insights into the possible etiology of neurodegenerative disease and highlights the importance of studying virus-host interactions in relevant model systems.}, } @article {pmid40672153, year = {2025}, author = {Sang, X and Jiao, H and Meng, Q and Fang, X and Sundaram, KS and Zhou, J and Xu, Y and Alvarado, AIW and Nuryyev, RL and Ourenik, J and Ourednik, V and Huang, IS and Liu, X and Mei, Y and Qian, T and Ciechanover, A and Pizzo, DP and Lane, MA and Zholudeva, LV and An, J and Snyder, EY and Hu, H and Huang, Z}, title = {The cryo-EM-delineated mechanism underlying mimicry of CXCR4 agonism enables widespread stem cell neuroprotection in a mouse model of ALS.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {40672153}, issn = {2692-8205}, support = {R01 GM057761/GM/NIGMS NIH HHS/United States ; }, abstract = {G-protein coupled receptors (GPCRs) are transmembrane proteins that mediate a range of signaling functions and, therefore, offer targets for a number of therapeutic interventions. Chemokine receptor CXCR4, a GPCR, plays versatile roles in normal and abnormal physiological processes. Synthetic CXCR4 antagonists have been extensively studied and approved for the clinical treatment of cancer and other diseases. We recently elucidated the structural mechanisms underlying CXCR4 antagonism using cryogenic electron microscopy (cryo-EM). CXCR4 agonism by synthetic molecules is an unanticipated therapeutic intervention we recently unveiled. The structural mechanisms underlying those actions remain poorly understood yet could help elucidate a new class of drugs. Here we demonstrate a synthetic dual-moiety strategy that combines simplified agonistic and antagonistic moieties taken from natural agonistic and antagonistic chemokines, respectively, to design de novo peptide mimics of biological function of natural CXCR4 agonist SDF-1α. Two peptides so generated, SDV1a and SDVX1 were shown to mimic the action of SDF-1α in activating CXCR4 signaling pathways and cell migration. The structural mechanism of these peptides in the mimicry of CXCR4 agonism was illustrated by cryo-EM structures of CXCR4 bound and activated by the peptides in the presence of G protein, revealing common interactions with the receptor by these peptides in comparison with SDF-1α that explain their close mimicry and conformational changes leading to CXCR4 signal activation. The therapeutic benefit of one of these peptides, SDV1a, was demonstrated in the SOD1[G93A] mouse model of the spinal motor neuron degenerative disease, amyotrophic lateral sclerosis (ALS) wherein the success of neuroprotective actions of transplanted human neural stem cells (hNSCs) is directly correlated with the expanse of diseased neuroaxis traversed by the donor cells; SDV1a enabled broader neuroprotective coverage while also permitting a much less invasive route of cell administration for extending life. Taken together, these results provide insights into the structural determinants of therapeutic CXCR4 agonism which may allow the design of adjunctive drugs that improve cell-based treatments of central nervous system (CNS) diseases.}, } @article {pmid40672150, year = {2025}, author = {Akiyama, T and Zeng, Y and Guo, C and Gautier, O and Koepke, LS and Bombosch, J and Sianto, O and Ross, JP and Hoang, PT and Zhao, LY and Spencer, C and Monje, M and Day, JW and Gitler, AD}, title = {KIF5A downregulation in spinal muscular atrophy links axonal regeneration defects with ALS.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2025.07.11.664426}, pmid = {40672150}, issn = {2692-8205}, abstract = {Spinal muscular atrophy (SMA) is a devastating neuromuscular disorder caused by mutations in the Survival Motor Neuron 1 (SMN1) gene, leading to decreased SMN levels and motor neuron dysfunction. SMN-restoring therapies offer clinical benefit, but the downstream molecular consequences of SMN reduction remain incompletely understood. Here, we demonstrate that SMN deficiency results in downregulation of KIF5A in human neurons and in a mouse model of SMA. We provide evidence that reduced SMN levels impair axon regeneration, which is rescued by KIF5A overexpression and that the RNA-binding protein SMN functions to stabilize KIF5A mRNA. These findings provide evidence of a molecular link between SMA and ALS pathophysiology, highlighting KIF5A as a new SMN target. Our findings suggest SMN-independent interventions targeting KIF5A could represent a complementary therapeutic approach for SMA and other motor neuron diseases.}, } @article {pmid40671798, year = {2025}, author = {Akan, T and Gelir, F and Aishwarya, R and Bhuiyan, MS and Bhuiyan, MAN}, title = {AFTG-Net: A Deep Attention-based Fusion Framework of Topological and Gradient Features for Pathological Image Analysis.}, journal = {Research square}, volume = {}, number = {}, pages = {}, pmid = {40671798}, issn = {2693-5015}, support = {P20 GM121307/GM/NIGMS NIH HHS/United States ; }, abstract = {Skeletal muscle pathology is observed by structural disruptions in sarcomeres, increased central nuclei, and changes in myofiber cross-sectional area. In order to classify amyotrophic lateral sclerosis (ALS), diabetes, and healthy controls, pathologists examine the changes in myofiber size using Wheat Germ Agglutinin (WGA) stained histopathological images of various skeletal muscles (quadriceps, gastrocnemius, tibialis anterior, extensor digitorum longus, and soleus). Histological image analysis of skeletal muscle pathology is laborious and subject to inter- and intra-user variability, which can affect diagnosis accuracy and consistency. Conventional techniques like ImageJ-based tools are time-consuming and produce varying outcomes due to their manual cell counting, segmentation, and thresholding. This study introduces AFTG-Net, an attention-based machine learning framework that classifies skeletal muscle histopathological images using complementary geometric and topological descriptors. The model uses globally structural information from Topological Data Analysis (TDA) based on persistent homology and local edge and texture patterns from the Histogram of Oriented Gradients. We suggest a cross-weighted fusion approach that uses cosine similarity to adaptively balance the contributions of these heterogeneous features in order to improve their discriminative power. This integration enables the model to effectively distinguish pathological changes associated with amyotrophic lateral sclerosis (ALS) and Type I diabetes from healthy muscle tissue. We conducted comprehensive comparisons with various state-of-the-art and baseline methods, such as traditional feature-based and deep learning models. We assessed all models by analyzing WGA-stained skeletal muscle images from wild-type and disease models (G93A*SOD1 for ALS and Akita for type 1 diabetes). AFTG-Net outperformed all other models by achieving 92% classification accuracy in distinguishing healthy and diseased muscle fibers. By reducing human intervention, subjectivity, and analysis time, AFTG-Net improves scalability and diagnostic consistency, making it a valuable tool for both biomedical research and clinical practice.}, } @article {pmid40671688, year = {2025}, author = {Masegosa, VM and Fritz, E and Corvalan, D and Rojas, F and Garcés, P and Navarro, X and Bloms-Funke, P and van Zundert, B and Herrando-Grabulosa, M}, title = {Novel Dual Mechanism GRT-X Agonist Acting on Kv7 Potassium Channel/Translocator Protein Receptor Prevents Motoneuron Degeneration Following Exposure to Mouse and Human Amyotrophic Lateral Sclerosis/Frontotemporal Dementia Astrocyte-Conditioned Media.}, journal = {ACS chemical neuroscience}, volume = {16}, number = {15}, pages = {2887-2900}, pmid = {40671688}, issn = {1948-7193}, mesh = {Animals ; *Astrocytes/metabolism/drug effects ; *Amyotrophic Lateral Sclerosis/metabolism/pathology ; Humans ; *Motor Neurons/drug effects/metabolism/pathology ; *Frontotemporal Dementia/metabolism/pathology ; Mice ; Rats ; Culture Media, Conditioned/pharmacology ; *Neuroprotective Agents/pharmacology ; *Receptors, GABA/metabolism ; Cells, Cultured ; Mice, Transgenic ; Spinal Cord/drug effects/metabolism ; Nerve Degeneration/metabolism ; Superoxide Dismutase-1/genetics ; *KCNQ2 Potassium Channel/agonists/metabolism ; Rats, Sprague-Dawley ; }, abstract = {Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) form a continuous spectrum of aggressive neurodegenerative diseases affecting primarily motoneurons (MNs) and cortical frontotemporal neurons. Noncell autonomous mechanisms contribute to ALS/FTD, wherein astrocytes release toxic factor(s) detrimental to MNs. Because of the multifactorial nature of ALS, single-pathway-focused therapies have limited effectiveness in improving ALS. Therefore, novel combinatorial therapies are currently being pursued. Here, we evaluated whether the simultaneous activation of two complementary targets, the voltage-gated potassium channels 7.2/3 (Kv7.2/3) and the mitochondrial translocator protein (TSPO), by a novel synthesized compound (GRT-X) is an effective neuroprotective treatment in ALS in vitro models. We exposed primary rat ventral spinal cord neuronal cultures and rat spinal cord organotypic cultures to astrocyte-conditioned medium derived from primary mouse ALS astrocytes expressing mutant human SOD1 (SOD1[G93A]-ACM) or from human-induced pluripotent stem cell (iPSC)-derived astrocytes carrying an ALS-causing mutation in SOD1 (SOD1[D90A]-ACM) or an ALS/FTD-causing mutation in TDP-43 (TDP43[A90 V]-ACM). We report that the diverse human and mouse ALS/FTD-ACMs compromise the MN viability. Remarkably, GRT-X led to consistent protection of MNs. Moreover, ALS/FTD-ACM increases oxidative stress levels, which are prevented with GRT-X treatment. Together, we show that the complementary activation of TSPO and Kv7.2/3 may offer a novel therapeutic strategy for ALS/FTD due to its capacity to protect MNs from noncell-autonomous toxicity induced by diseased astrocytes.}, } @article {pmid40670663, year = {2025}, author = {Tanaka, Y and Sunamura, N and Kajitani, R and Ikeguchi, M and Kunimoto, R}, title = {Long-read RNA sequencing unveils a novel cryptic exon in MNAT1 along with its full-length transcript structure in TDP-43 proteinopathy.}, journal = {Communications biology}, volume = {8}, number = {1}, pages = {1056}, pmid = {40670663}, issn = {2399-3642}, mesh = {Humans ; *Exons ; Amyotrophic Lateral Sclerosis/genetics ; *TDP-43 Proteinopathies/genetics ; *DNA-Binding Proteins/genetics/metabolism ; RNA Splicing ; Sequence Analysis, RNA ; Induced Pluripotent Stem Cells/metabolism ; Motor Neurons/metabolism ; }, abstract = {Understanding the role of transcript isoforms is essential for elucidating disease mechanisms. TDP-43 regulates RNA splicing, and its dysfunction in neurons is a hallmark of some neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and frontotemporal degeneration (FTD). While an association between TDP-43-dependent cryptic exons and disease pathogenesis has been suggested, an approach to investigate how cryptic exons disrupt transcript isoforms has yet to be established. In this study, we developed IsoRefiner, a novel method for identifying full-length transcript structures using long-read RNA-seq. Leveraging this method, we performed long-read RNA-seq, guided by prior short-read RNA-seq, to comprehensively determine the full-length structures of aberrant transcripts due to TDP-43 dysregulation in human iPSC-derived motor neurons. We identified a novel TDP-43-dependent cryptic exon in the MNAT1 gene, along with its full-length transcript structure. Furthermore, we confirmed the presence of the MNAT1 cryptic exon in patients with ALS and FTD. Our findings deepen understanding of TDP-43 proteinopathy and advance splicing research.}, } @article {pmid40669676, year = {2025}, author = {Su, X and Tan, X and Wang, Y and Liang, W and Wang, D and Huo, D and Wang, H and Qi, Y and Zhang, W and Han, L and Zhang, D and Wang, M and Xu, J and Feng, H}, title = {DAPK1 induces motor neuron apoptosis in hSOD1[G93A]-linked amyotrophic lateral sclerosis via regulating the Xiap/JNK pathway.}, journal = {Molecular and cellular neurosciences}, volume = {}, number = {}, pages = {104029}, doi = {10.1016/j.mcn.2025.104029}, pmid = {40669676}, issn = {1095-9327}, abstract = {Death-associated protein kinase 1 (DAPK1) is critically involved in regulating cell death in various neurodegenerative disorders. However, the role of DAPK1 in the pathogenesis of amyotrophic lateral sclerosis (ALS) remains unclear. Here, we found that the expression of DAPK1 significantly increased in ALS, showing a negative correlation with miR-501-3p. Upregulating DAPK1 led to an increase in motor neuron apoptosis by inhibiting Xiap. Conversely, silencing of DAPK1 protected motor neurons against hSOD1[G93A]-induced apoptosis by activating Xiap. Furthermore, we demonstrate that the neuroprotective impact of DAPK1-knockdown was inhibited by Embelin, an inhibitor of Xiap. These results suggest that modulating the DAPK1/Xiap signaling cascade protects motor neurons from apoptosis, indicating its potential as a therapeutic target in ALS. Significantly, these findings offer new directions for treatment options for ALS patients.}, } @article {pmid40669270, year = {2025}, author = {Martinelli, I and Simonini, C and Zucchi, E and Gianferrari, G and Bedin, R and Ghezzi, A and Mandrioli, J}, title = {Predictors from systemic and neuro-inflammation in amyotrophic lateral sclerosis: A monocentric experience.}, journal = {Journal of neuroimmunology}, volume = {406}, number = {}, pages = {578683}, doi = {10.1016/j.jneuroim.2025.578683}, pmid = {40669270}, issn = {1872-8421}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/blood/diagnosis/immunology ; Female ; Male ; Middle Aged ; Retrospective Studies ; Aged ; Biomarkers/blood ; *Neuroinflammatory Diseases/blood/diagnosis ; Adult ; Prognosis ; alpha 1-Antitrypsin/blood ; Inflammation/blood ; Chitinase-3-Like Protein 1/blood ; Cohort Studies ; Membrane Glycoproteins ; Receptors, Immunologic ; }, abstract = {While the role of systemic and neuroinflammatory players is actually consolidated in amyotrophic lateral sclerosis (ALS) pathogenesis, a representative and reliable panel of inflammatory prognostic biomarkers is still lacking. This retrospective study on 182 ALS patients from the Modena ALS Center, investigates biomarkers of axonal injury (neurofilaments) and microglial and astrocytic activation (SerpinA1, TREM2, CHI3L1, OPN and S100B, respectively). In a subpopulation of patients, we examined blood count-derived parameters, including the Systemic-Immune-Inflammation index (SII), Systemic Inflammation Response Index (SIRI) and Aggregate Systemic Inflammation Index (AISI). All variables were analyzed for association with clinical features in the entire cohort and then in sex- and age-based subgroups. SerpinA1CSF was significantly lower in females [4.43 μg/ml (IQR 2.76-6.3) vs 5.61 μg/ml (IQR 3.39-9.16),p = 0.032], while SII indexes was oppositely distributed [higher in females, 540.67 (IQR 363.05-807.24) vs 384.89 (IQR 307.5-578.52),p = 0.015]. In univariate survival analysis, without overcoming neurofilaments, SIRI (HR 1.43, 95 %CI 1.03-1.966,p = 0.03), AISI (HR 1.002, 95 %CI 1.001-1.003, p = 0.002) and SII (HR 1.001, 95 %CI 1.0003-1.001,p = 0.003) impact negatively on survival, with AISI retaining its power at multivariate analysis (HR 1.002, 95 %CI 1.0004-1.001,p = 0.012). SerpinA1CSF levels influenced survival only for females (HR 1.042, 95 %CI 1.0065-1.078,p = 0.02), in a similar manner of SIRI (HR 1.483, 95 %CI 1.082-2.0334,p = 0.014) and SII (HR 1.00099, 95 %CI 1.0008-1.003,p = 0.001). Our data revealed the influence of sex on survival by SerpinA1CSF, CHI3L1CSF and systemic biomarkers in females. However, both neurofilaments and CHI3L1CSF outperform the other neuroinflammatory biomarkers at predicting rate of disease progression, so the prognostic meaning of these measure alone remains unconclusive, requiring larger collaborative studies.}, } @article {pmid40668826, year = {2025}, author = {Komarova, K and Gelfand, NA and Remacle, F and Levine, RD and Chakraborty, S and Jackson, TL and Kostko, O and Thiemens, MH}, title = {Photoselective isotope fractionation dynamics of N2 with cosmo and atmospheric chemistry perspectives.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {122}, number = {29}, pages = {e2511172122}, pmid = {40668826}, issn = {1091-6490}, support = {2019722//BSF-NSF/ ; T0205.20//FNRS | Fonds pour la Formation à la Recherche/ ; DE-AC02-05CH11231//DOE office of Science/ ; 2009959//NSF-BSF/ ; }, abstract = {Stable isotope ratio measurements provide valuable insights into a broad range of natural processes, from planetary atmospheres and climate to interstellar chemistry. Nitrogen, which has two stable isotopes, exhibits varying isotope ratios across the solar system. To model these observations, the isotope fraction as a function of energy is essential. At the Advanced Light Source (ALS), we measured the photodissociation of molecular nitrogen (N2) with vacuum UV photons where a single photon is sufficiently energetic to dissociate the strong bond. The nitrogen atoms produced are scavenged with H2 to form ammonia, whose isotopic makeup is determined. Blending the experiments with dynamical computations that include the shielding of light, we examine the isotopic composition and electronic atomic states produced. The measured photodissociation of N2 at a natural isotopic composition with a frequency broad light beam exceptionally strongly favors the formation of the heavier nitrogen isotope, [15]N. Computations concur and suggest that the maximum in the quantum yield reflects significant variations in the specific electronic quantum states of the product N atoms that have quite different reactivities. Our quantum computations show that at similar energies, photodissociation of [14]N[14]N and [15]N[14]N can lead to different product channels. The computed dynamics include extensive state-selective spin-orbit and nonadiabatic couplings affecting the light absorption and dissociation pathways that proceed via the triplet manifold of states. Our results are relevant for future exploration missions, both in situ and sample-return and for other molecules such as O2 and CO.}, } @article {pmid40667260, year = {2025}, author = {Ghayal, NB and Crook, RJ and Jain, A and Sachdeva, G and Roemer, SF and Sekiya, H and DeTure, MA and Baker, M and Coster, W and Oskarsson, BE and Josephs, KA and Rademakers, R and van Blitterswijk, M and Dickson, DW}, title = {Expanding the spectrum of annexin A11 proteinopathy in frontotemporal lobar degeneration and motor neuron disease.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2025.06.26.661831}, pmid = {40667260}, issn = {2692-8205}, abstract = {Aggregation of TAR DNA-binding protein 43 (TDP-43) is strongly associated with frontotemporal lobar degeneration (FTLD-TDP), motor neuron disease (MND-TDP), and overlap disorders like FTLD-MND. Three major forms of motor neuron disease are recognized and include primary lateral sclerosis (PLS), amyotrophic lateral sclerosis (ALS), and progressive muscular atrophy (PMA). Annexin A11 (ANXA11) is understood to aggregate in amyotrophic lateral sclerosis (ALS-TDP) associated with pathogenic variants in ANXA11 , as well as in FTLD-TDP type C. Given these observations and recent reports of ANXA11 variants in patients with semantic variant frontotemporal dementia (svFTD) and FTD-MND presentations, we sought to characterize ANXA11 proteinopathy in an autopsy cohort of 379 cases with FTLD-TDP, as well as FTLD-MND and MND-TDP cases subclassified neuropathologically into PLS, ALS, and PMA. All FTLD-TDP type C cases had ANXA11 proteinopathy. However, ANXA11 proteinopathy was present in over 40% of FTLD-MND and in 38 out of 40 FTLD-PLS cases (95%), of which 80% had TDP type B or an unclassifiable TDP-43 proteinopathy and 15% had TDP type C. Genetic analyses excluded pathogenic ANXA11 variants in all ANXA11-positive cases. We thus demonstrated novel forms of ANXA11 proteinopathy strongly associated with FTLD-PLS, but not with TDP type C or pathogenic ANXA11 variants. Given the emerging relationship of ANXA11 in TDP-43 proteinopathies, we propose that TDP-43 and ANXA11 proteinopathy (TAP) comprises the molecular pathology of cases with abundant inclusions that are co-immunoreactive for both proteins and we subclassify three types of TAP based on distinct clinical and neuropathologic features.}, } @article {pmid40667180, year = {2025}, author = {Tam, SB and Waldeck, NJ and Wright, M and Baker, EM and Kiskinis, E and Bass, J and Kalb, RG}, title = {Cholinergic neuron circadian clock mediates RNA-binding protein function and contributes to ALS disease phenotypes.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2025.05.06.652480}, pmid = {40667180}, issn = {2692-8205}, abstract = {Circadian clocks are encoded by a transcription-translation feedback loop that aligns physiological processes with the solar cycle. Previous work linking the circadian clock to the regulation of RNA-binding proteins (RBPs) and alternative splicing provides a foundation for the vital examination of their mechanistic connections in the context of amyotrophic lateral sclerosis (ALS)-a fatal neurodegenerative disease characterized by disrupted RBP function. Here, we reveal enrichment of genes associated with ALS and other neurodegenerative diseases in the spinal cord cholinergic neuron rhythmic transcriptome. We demonstrate that there is circadian regulation of ALS-linked RBPs and rhythmic alternative splicing of genes involved in intracellular transport (Aftph and Mvb12a), microtubule cytoskeleton organization (Limch1 and Drc3), and synaptic function (Sipa1l2) in this neuronal sub-type. Further, we show that the cholinergic neuron clock regulates sporadic ALS-associated changes in cytoskeleton and neuromuscular junction synapse gene expression. Finally, we report that cell-type-specific Bmal1 -deletion (i) increases lumbar spinal cord motor neuron loss and sciatic nerve axon degeneration, (ii) drives alternative splicing of genes encoding ALS-linked RBPs (Matr3 and Srsf7), and (iii) drives alternative splicing of genes associated with microtubule transport and postsynaptic organization. Our results establish a role for the cholinergic neuron circadian clock in RBP function and ALS disease phenotypes.}, } @article {pmid40667053, year = {2025}, author = {Chizari, S and Zanovello, M and Kong, S and Saigal, V and Brown, AL and Turchetti, V and Zampedri, L and Skorupinska, I and Minicuci, GM and Paron, F and Tonin, P and Marchetto, G and Li, Z and Colón-Mercado, JM and Dattilo, D and Barattucci, S and Gatt, A and Qi, A and Hanna, M and Ward, M and Petrucelli, L and Romano, M and Vattemi, G and Buratti, E and Malapsina, A and Merve, A and Machado, PM and Soraru, G and Fratta, P and Jiang, N}, title = {TDP-43 pathology induces CD8[+] T cell activation through cryptic epitope recognition.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {40667053}, issn = {2692-8205}, support = {S10 OD026986/OD/NIH HHS/United States ; T32 AI055428/AI/NIAID NIH HHS/United States ; U54 NS123743/NS/NINDS NIH HHS/United States ; }, abstract = {Aggregation and nuclear depletion of the RNA binding protein TDP-43 are the crucial pathological features of amyotrophic lateral sclerosis (ALS) and inclusion body myositis (IBM), two degenerative diseases of the CNS and muscle. The loss of TDP-43 nuclear function results in the aberrant inclusion of cryptic exons in mRNA transcripts, leading to the expression of de novo proteins. Clonally expanded and highly differentiated CD8[+] T cells have been observed in individuals with TDP-43 proteinopathies and therapeutics modulating the T cell response have recently been found to extend survival. However, the target antigens mediating T cell activation have remained elusive. Here, we investigate whether the de novo proteins induced by aberrant cryptic splicing due to TDP-43 nuclear loss can act as neo-antigens. We detect the HDGFL2 cryptic peptide and multiple other TDP-43 cryptic exons in IBM skeletal muscle, where their presence correlates with enrichment of T cells and class I antigen presentation pathways. Furthermore, we identify epitopes deriving from HDGFL2 and IGLON5 cryptic peptides which are recognized by clonally expanded and functionally differentiated populations of CD8[+] T cells in ALS and IBM Patients. Finally, we demonstrate that T cells engineered to express the identified TCRs can bind and activate in response to the cryptic peptide derived epitopes (cryptic epitopes) and are able to kill TDP-43 deficient astrocytes. This work identifies for the first time specific T cell antigens in ALS and IBM, directly linking adaptive immune response to TDP-43 pathology.}, } @article {pmid40667039, year = {2025}, author = {Sinha, IR and Ye, Y and Li, Y and Sandal, PS and Wong, PC and Sun, S and Ling, JP}, title = {Inhibition of nonsense-mediated decay in TDP-43 deficient neurons reveals novel cryptic exons.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {40667039}, issn = {2692-8205}, support = {R01 AG078948/AG/NIA NIH HHS/United States ; RF1 NS095969/NS/NINDS NIH HHS/United States ; RF1 NS129878/NS/NINDS NIH HHS/United States ; U01 FD008129/FD/FDA HHS/United States ; }, abstract = {TAR DNA-binding protein 43 kDa (TDP-43) is an essential splicing repressor whose loss of function underlies the pathophysiology of amyotrophic lateral sclerosis and frontotemporal dementia (ALS-FTD). Nuclear clearance of TDP-43 disrupts its function and leads to the inclusion of aberrant cryptic exons. These cryptic exons frequently introduce premature termination codons resulting in the degradation of affected transcripts through nonsense-mediated mRNA decay (NMD). Conventional RNA sequencing approaches thus may fail to detect cryptic exons that are efficiently degraded by NMD, precluding identification of potential therapeutic targets. We generated a comprehensive set of neuronal targets of TDP-43 in human iPSC-derived i[3]Neurons (i[3]N) by combining TDP-43 knockdown with inhibition of multiple factors essential for NMD, revealing novel cryptic targets. We then restored expression of selected NMD targets in TDP-43 deficient i[3]Ns and determined which genes improved neuronal viability. Our findings highlight the role of NMD in masking cryptic splicing events and identify novel potential therapeutic targets for TDP-43-related neurodegenerative disorders.}, } @article {pmid40666348, year = {2025}, author = {Johari, M and Folland, C and Saito, Y and Oud, MM and Parmar, JM and Töpf, A and Kurbatov, S and Ampleeva, M and Zakharova, EY and Chekmareva, IA and Shirokova, KS and Atiakshin, D and Gardeitchik, T and Kamsteeg, EJ and Medici, E and Kaat, LD and Bruels, CC and Stafki, SA and Estrella, EA and Littel, HR and Kunkel, LM and Kang, PB and Osei-Owusu, I and Pais, L and O'Leary, M and Austin-Tse, C and O'Donnell-Luria, A and Mangilog, B and Radio, FC and D'Amico, A and Ciolfi, A and Tartaglia, M and Perrin, A and Van Goethem, C and Sole, G and Martin-Négrier, ML and Cossée, M and Genetti, CA and Valivullah, ZM and Milic, V and Kovacevic, G and Kosac, A and Moreno, CAM and Camelo, CG and Zanoteli, E and Fahey, MC and Beggs, AH and Vissing, J and Straub, V and Savarese, M and Tasca, G and Voermans, N and Laing, NG and Udd, B and Nishino, I and Ravenscroft, G}, title = {Missense variants in TUBA4A cause myo-tubulinopathies.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, pmid = {40666348}, support = {P50 HD105351/HD/NICHD NIH HHS/United States ; R01 HG009141/HG/NHGRI NIH HHS/United States ; U01 HG011755/HG/NHGRI NIH HHS/United States ; UM1 HG008900/HG/NHGRI NIH HHS/United States ; }, abstract = {Tubulinopathies encompass a wide spectrum of disorders resulting from variants in genes encoding α- and β-tubulins, the key components of microtubules. While previous studies have linked de novo or dominantly inherited TUBA4A missense variants to neurodegenerative phenotypes, including amyotrophic lateral sclerosis, frontotemporal dementia, hereditary spastic ataxia, and more recently, an isolated report of congenital myopathy, the full phenotypic and genotypic spectrum of TUBA4A-related disorders remains incompletely characterised. In this multi-centre study, we identified 13 novel TUBA4A missense variants in 31 individuals from 19 unrelated families. Remarkably, affected individuals in 17 families presented with a primary axial myopathy without any identified CNS involvement or history of such disease. In the remaining two families, we observed probands with cerebellar ataxia and epilepsy accompanying proximal and axial muscle weakness, establishing the first documented association between TUBA4A variants and multisystem proteinopathy. Our cohort exhibited diverse genotypes and associated inheritance patterns: four families demonstrated autosomal dominant transmission through heterozygous variants in TUBA4A, three probands had homozygous TUBA4A variants, where the biallelic genotype was found to be associated with the disease, and the heterozygous carriers were asymptomatic; five probands carried de novo variants, and nine probands with heterozygous TUBA4A variants were classified as "isolated-sporadic cases" where parental samples were unavailable. Clinical phenotypes ranged from mild to severe myopathy, predominantly affecting the axial and paraspinal muscles. We observed a range of disease onset, from congenital to late adulthood. Creatine kinase levels were also variable, ranging from normal to highly elevated. Cardiac function remained preserved across the cohort. Muscle biopsies revealed a range of pathologies, including myofibre size variation, myofibre atrophy, nemaline bodies, core-like regions, internal nuclei, and endomysial fibrosis. Immunohistochemical staining showed evidence of proteinopathy, with autophagic features and TUBA4A accumulation in patient myofibres. Complementary in silico and in vitro investigations suggested that the identified TUBA4A substitutions cause significant protein abnormalities and may differentially impact microtubule dynamics. Our findings establish myo-tubulinopathies as distinct clinical entities, encompassing both primary myopathies and multisystem proteinopathies with muscle involvement. This study broadens the phenotypic and genotypic spectrum of TUBA4A-related disorders beyond autosomal dominant or de novo mechanisms and neurodegenerative presentations. These results underscore the importance of considering TUBA4A variants in the differential diagnosis of axial myopathies and multisystem proteinopathies, regardless of central nervous system (CNS) involvement.}, } @article {pmid40666341, year = {2025}, author = {Petrozziello, T and Mizerak, E and Krishnamoorthy, A and Donahue, RA and Castillo Torres, AL and Monsanto, RZB and Hammerschlag, BL and Fillingham, B and Kivisäkk, P and Timmons, J and Fox, K and Arnold, SE and Cohen, J and Klee, J and Paganoni, S and Cudkowicz, ME and Chibnik, LB and Berry, JD and Sadri-Vakili, G}, title = {Plasma tau and phosphorylated tau at T181 are altered in amyotrophic lateral sclerosis.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, doi = {10.1101/2025.06.26.25330363}, pmid = {40666341}, abstract = {There is an unmet need for reliable biomarkers for amyotrophic lateral sclerosis (ALS). Recent studies have demonstrated that the levels of the microtubule-associated protein tau, are altered in plasma and cerebrospinal fluid (CSF) from people with ALS. Our previous findings demonstrated that while the ratio between tau and phosphorylated tau at T181 (pTau-T181) is decreased, increases in CSF tau correlated with faster disease progression in people with ALS. Here, we measured tau and pTau-T181 in plasma samples from participants with ALS and healthy controls (HC) using two methods (Quanterix Simoa and Meso Scale Discovery, MSD). Using both assays, there was an increase in pTau-T181 levels and in the pTau-T181:tau ratio in ALS compared to HC andlarger increases in pTau-T181 and pTau-T181:tau ratio at baseline correlated with faster ALS progression. Plasma total tau levels were increased in ALS compared to HC on the MSD assay and decreased on Quanterix Simoa assay. Collectively, our results suggest that plasma pTau-T181 levels are increased in ALS. Future studies should aim to clarify its role as a diagnostic or prognostic biomarker for ALS.}, } @article {pmid40665686, year = {2025}, author = {Lee, B and Cho, ST and Kim, R and Chung, KW and Kwon, TJ and Kim, UK and Kim, YR and Choi, BO and Park, JS}, title = {DCTN1-associated neurological disorder with symptoms similar to spinal bulbar muscular atrophy.}, journal = {Journal of neuromuscular diseases}, volume = {}, number = {}, pages = {22143602251352989}, doi = {10.1177/22143602251352989}, pmid = {40665686}, issn = {2214-3602}, abstract = {BackgroundDynactin 1 (DCTN1) mutations are associated with diverse neurological disorders, including distal hereditary motor neuropathy, Perry syndrome, and amyotrophic lateral sclerosis. This study focused on a family with symptoms resembling spinal and bulbar muscular atrophy, showing severe vocal cord paralysis, to understand DCTN1-related neurological disorders in Koreans.MethodClinical examinations revealed variable phenotypes, such as proximal limb weakness, chronic hypercapnia, and gynecomastia, alongside vocal cord paralysis. Whole-exome sequencing identified a missense mutation, c.1175G > A, in DCTN1. Three more Korean families with the same mutation were analyzed to explore a potential founder effect. Microsatellite analysis indicated a shared haplotype, suggesting a common genetic origin.ResultThis study identified a missense mutation, c.1175G > A, in DCTN1 in the initial family with features resembling spinal and bulbar muscular atrophy. The mutation was also present in three other Korean families, indicating a potential founder effect. Microsatellite analysis confirmed a shared haplotype among these families. Meanwhile, the patients also manifested additional clinical features such as peripheral neuropathy and gynecomastia.ConclusionThis study highlights clinical heterogeneity in Korean patients with DCTN1-associated neurological disorders and identifies a potential founder mutation, c.1175G > A, expanding the clinical spectrum of DCTN1 mutations with clinical features of spinal bulbar muscular atrophy. Understanding such genetic and clinical diversity is crucial for accurate diagnoses and management, with implications for future research and therapeutic strategies.}, } @article {pmid40665049, year = {2025}, author = {Shvetcov, A and Johnson, ECB and Winchester, LM and Walker, KA and Wilkins, HM and Thompson, TG and Rothstein, JD and Krish, V and Imam, FB and , and Burns, JM and Swerdlow, RH and Slawson, C and Finney, CA}, title = {APOE ε4 carriers share immune-related proteomic changes across neurodegenerative diseases.}, journal = {Nature medicine}, volume = {31}, number = {8}, pages = {2590-2601}, pmid = {40665049}, issn = {1546-170X}, support = {MRF2040081//Department of Health | National Health and Medical Research Council (NHMRC)/ ; K08AG08604//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; R01AG089497//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; P50AG025688//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; P30AG072973//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; R21TR003589//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; R01AG07816//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; U19AG068054//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; R35NS132179//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; R01AG064227//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; 23AARG-1023/ALZ/Alzheimer's Association/United States ; }, abstract = {The APOE ε4 genetic variant is the strongest genetic risk factor for late-onset Alzheimer's disease (AD) and is increasingly being implicated in other neurodegenerative diseases. Using the Global Neurodegeneration Proteomics Consortium SomaScan dataset covering 1,346 cerebrospinal fluid (CSF) and 9,924 plasma samples, we used machine learning-based proteome profiling to identify an APOE ε4 proteomic signature shared across individuals with AD, frontotemporal dementia (FTD), Parkinson's disease dementia (PDD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and nonimpaired controls. This signature was enriched in pro-inflammatory immune and infection pathways as well as immune cells, including monocytes, T cells and natural killer cells. Analysis of the dorsolateral prefrontal cortex proteome for 262 donors from the Accelerating Medicines Partnership for AD UPenn Proteomics Study revealed a consistent APOE ε4 phenotype, independent of neurodegenerative pathology, including amyloid-β tau and gliosis for all diseases, as well as TDP-43 in ALS and FTD cases, and α-synuclein in PD and PDD cases. While systemic proteomic changes were consistent across APOE ε4 carriers, their relationship with clinical and lifestyle factors, such as hypertension and smoking, varied by disease. These findings suggest APOE ε4 confers a systemic biological vulnerability that is necessary but not sufficient for neurodegeneration, emphasizing the need to consider gene-environment interactions. Overall, our study reveals a conserved APOE ε4-associated pro-inflammatory immune signature persistent across the brain, CSF and plasma irrespective of neurodegenerative disease, highlighting a fundamental, disease-independent biological vulnerability to neurodegeneration. This work reframes APOE ε4 as a pleiotropic immune modulator rather than an AD-specific risk gene, providing a foundation for precision biomarker development and early intervention strategies across neurodegenerative diseases.}, } @article {pmid40665048, year = {2025}, author = {Imam, F and Saloner, R and Vogel, JW and Krish, V and Abdel-Azim, G and Ali, M and An, L and Anastasi, F and Bennett, D and Pichet Binette, A and Boxer, AL and Bringmann, M and Burns, JM and Cruchaga, C and Dage, JL and Farinas, A and Ferrucci, L and Finney, CA and Frasier, M and Hansson, O and Hohman, TJ and Johnson, ECB and Kivimaki, M and Korologou-Linden, R and Ruiz Laza, A and Levey, AI and Liepelt-Scarfone, I and Lu, L and Mattsson-Carlgren, N and Middleton, LT and Nho, K and Oh, HS and Petersen, RC and Reiman, EM and Robinson, O and Rothstein, JD and Saykin, AJ and Shvetcov, A and Slawson, C and Smets, B and Suárez-Calvet, M and Tijms, BM and Timmers, M and Vieira, F and Vilor-Tejedor, N and Visser, PJ and Walker, KA and Winchester, LM and Wyss-Coray, T and Yang, C and Bose, N and Lovestone, S and , }, title = {The Global Neurodegeneration Proteomics Consortium: biomarker and drug target discovery for common neurodegenerative diseases and aging.}, journal = {Nature medicine}, volume = {31}, number = {8}, pages = {2556-2566}, pmid = {40665048}, issn = {1546-170X}, abstract = {More than 57 million people globally suffer from neurodegenerative diseases, a figure expected to double every 20 years. Despite this growing burden, there are currently no cures, and treatment options remain limited due to disease heterogeneity, prolonged preclinical and prodromal phases, poor understanding of disease mechanisms, and diagnostic challenges. Identifying novel biomarkers is crucial for improving early detection, prognosis, staging and subtyping of these conditions. High-dimensional molecular studies in biofluids ('omics') offer promise for scalable biomarker discovery, but challenges in assembling large, diverse datasets hinder progress. To address this, the Global Neurodegeneration Proteomics Consortium (GNPC)-a public-private partnership-established one of the world's largest harmonized proteomic datasets. It includes approximately 250 million unique protein measurements from multiple platforms from more than 35,000 biofluid samples (plasma, serum and cerebrospinal fluid) contributed by 23 partners, alongside associated clinical data spanning Alzheimer's disease (AD), Parkinson's disease (PD), frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). This dataset is accessible to GNPC members via the Alzheimer's Disease Data Initiative's AD Workbench, a secure cloud-based environment, and will be available to the wider research community on 15 July 2025. Here we present summary analyses of the plasma proteome revealing disease-specific differential protein abundance and transdiagnostic proteomic signatures of clinical severity. Furthermore, we describe a robust plasma proteomic signature of APOE ε4 carriership, reproducible across AD, PD, FTD and ALS, as well as distinct patterns of organ aging across these conditions. This work demonstrates the power of international collaboration, data sharing and open science to accelerate discovery in neurodegeneration research.}, } @article {pmid40664547, year = {2025}, author = {Müllhaupt, G and Hechelhammer, L and Graf, N and Mordasini, L and Schmid, HP and Engeler, DS and Abt, D}, title = {Reply to Francesco Montorsi, Edoardo Pozzi, Marco Bianchi, et al's Letter to the Editor re: Gautier Müllhaupt, Lukas Hechelhammer, Nicole Graf, et al. Prostatic Artery Embolisation Versus Transurethral Resection of the Prostate for Benign Prostatic Obstruction: 5-year Outcomes of a Randomised, Open-label, Noninferiority Trial. Eur Urol Focus 2024;10:788-95.}, journal = {European urology focus}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.euf.2025.06.017}, pmid = {40664547}, issn = {2405-4569}, } @article {pmid40664152, year = {2025}, author = {Keivan Behjou, N and Seyedalipour, B and Hosseini Faradonbeh, SM and Hosseinkhani, S and Chaeichi, MJ}, title = {Exploring the role of ethylammonium bromide as an ionic liquid in amyloid aggregation modulation for ALS-linked hSOD1 E49K mutant.}, journal = {Bioorganic chemistry}, volume = {163}, number = {}, pages = {108740}, doi = {10.1016/j.bioorg.2025.108740}, pmid = {40664152}, issn = {1090-2120}, mesh = {Humans ; *Amyloid/metabolism/antagonists & inhibitors ; *Amyotrophic Lateral Sclerosis/genetics/metabolism/drug therapy ; Dose-Response Relationship, Drug ; *Ionic Liquids/chemistry/pharmacology ; Molecular Dynamics Simulation ; Molecular Structure ; Mutation ; Protein Aggregates/drug effects ; *Quaternary Ammonium Compounds/chemistry/pharmacology ; Structure-Activity Relationship ; *Superoxide Dismutase-1/genetics/metabolism/antagonists & inhibitors ; Proto-Oncogene Proteins c-akt ; }, abstract = {Ionic liquids (ILs) offer a diverse and tunable approach to inhibiting amyloid protein formation, providing new strategies to develop anti-amyloidogenic agents for amyloid-based diseases, as explored in protein-IL research. This study explores the formation of amyloid aggregates of the E49K mutant under amyloidogenic conditions and evaluates the inhibitory potential of ethylammonium bromide (EABr) as an anti-amyloidogenic agent relevant to ALS pathology. The effect of EABr was studied using molecular dynamics simulations, FTIR spectroscopy, ANS fluorescence, ThT fluorescence, and TEM imaging. EABr promotes the formation of compact structures by reducing the exposure of contagious hydrophobic pockets in the E49K mutant aggregates, as monitored by ANS fluorescence. EABr binds with moderate affinity to the E49K mutant forms, inhibiting fibrillation by stabilizing aggregation-prone regions, as shown in fluorescence quenching. The decrease in ThT fluorescence intensity and the inhibition of fibril formation in a concentration-dependent manner highlight the interaction of EABr with the E49K mutant throughout the incubation period. TEM images during the saturation phase provide compelling evidence that EABr inhibits the formation of amyloid fibrils in the E49K mutant, thus supporting ThT analysis results. These findings demonstrate that EABr can inhibit amyloid formation of the E49K SOD1 mutant in vitro, supporting its potential as a lead compound for further pharmacological studies.}, } @article {pmid40664112, year = {2025}, author = {Sahoo, BR and Bardwell, JC}, title = {Protein and RNA chaperones.}, journal = {Molecular aspects of medicine}, volume = {104}, number = {}, pages = {101384}, doi = {10.1016/j.mam.2025.101384}, pmid = {40664112}, issn = {1872-9452}, mesh = {Humans ; *Molecular Chaperones/metabolism/chemistry ; *RNA/metabolism/chemistry ; G-Quadruplexes ; Animals ; Protein Folding ; Protein Aggregates ; *RNA-Binding Proteins/metabolism/chemistry ; Amyotrophic Lateral Sclerosis/metabolism ; }, abstract = {Cells preserve macromolecular homeostasis by utilizing molecular chaperones that prevent aggregation or promote correct folding of protein and RNA. Here we discuss non-traditional proteinaceous chaperones like RNA-binding chaperones that work by modulating RNA structure, preventing aberrant interactions, and regulating intracellular granule dynamics. We also discuss the chaperone functions of other macromolecules such as nucleic acids, and in particular G-quadruplexes, which are very effective at preventing protein aggregation and accelerating protein folding. These chaperones are particularly important in G-quadruplex linked amyloid aggregation and repeat-expansion diseases such as Parkinson's disease and amyotrophic lateral sclerosis, where RNA aggregation and misfolded protein accumulation co-occur. By comparing protein and non-protein chaperone systems, we highlight the principles that underlie chaperone action across molecular classes.}, } @article {pmid40663766, year = {2025}, author = {Matthews, AM and Whiteley, AM}, title = {UBQLN2 in neurodegenerative disease: mechanistic insights and emerging therapeutic potential.}, journal = {Biochemical Society transactions}, volume = {}, number = {}, pages = {}, doi = {10.1042/BST20253053}, pmid = {40663766}, issn = {1470-8752}, abstract = {Ubiquilins (UBQLNs) regulate cellular protein turnover by shuttling proteins, or 'clients', to the proteasome or autophagy pathways for degradation. Of the five different UBQLN genes in humans, UBQLN2 is the most highly expressed in the nervous system and muscle tissue and has been linked to multiple neurodegenerative diseases. In particular, point mutations of UBQLN2 cause an X-linked, dominant form of amyotrophic lateral sclerosis (ALS), ALS with frontotemporal dementia (ALS/FTD), or FTD. Failed protein degradation is a hallmark of many neurodegenerative diseases, including ALS and FTD; however, it is not clear exactly how ALS/FTD-associated UBQLN2 mutations contribute to pathogenesis. Recent studies have revealed the complexity of UBQLN2 biology and allow deeper understanding as to how UBQLN2 dysfunction may contribute to neurodegenerative disease. UBQLN2 is necessary for mitochondrial protein degradation and for regulating mitochondrial turnover, both of which are essential for motor neurons and have been implicated in the pathogenesis of ALS. Stress granule (SG) formation and regulation are also affected by UBQLN2 mutations, and their dysregulation may contribute to the toxic protein aggregation and SG changes observed in neurodegenerative disease. Finally, there are compelling links connecting UBQLN2 dysfunction with changes to downstream neuronal morphology, function, and behavior. This review will detail the emerging consensus on how UBQLN2 protects against neurodegenerative disease and will provide insights into potential therapeutic approaches.}, } @article {pmid40661843, year = {2025}, author = {Malmström, N and Öhlén, J and Nilsson, S and Nygren, I and Andersen, PM and Jakobsson Larsson, B and Ozanne, A}, title = {Transformed Parenthood in the Face of ALS: A Profound Struggle for Both Ill Parents and Co-parents.}, journal = {Global qualitative nursing research}, volume = {12}, number = {}, pages = {23333936251348143}, pmid = {40661843}, issn = {2333-3936}, abstract = {When a parent is diagnosed with a progressive, fatal neurodegenerative disease, such as amyotrophic lateral sclerosis (ALS), it can have major effects on the family's health. Parenthood itself may also be affected, potentially fueling an urgent need for support from healthcare. Research focusing on this group of parents is nevertheless limited. The aim of this study was to illuminate the meaning of parenthood when a parent has ALS, from the perspective of ill parents and co-parents. An interpretive qualitative study was conducted, using data gathered from interviewing 26 parents (13 ill parents and 13 co-parents) with children living at home in Sweden. Applying a phenomenological hermeneutical analysis, structural analyses depicted the burdensome, complex impact that ALS can have on parenthood, redefining its meaning while forcing parents to face the difficult challenges it brings. The interpreted whole revealed how navigating this transformed parenthood meant a profound struggle, as the parents strived to balance their own emotional pain from grief and worry with remaining stable and supportive for their children. To promote the health of families affected by ALS, more proactive, tailored support is needed within ALS nursing, along with early integration of a palliative approach and attention to the parental perspective.}, } @article {pmid40661641, year = {2025}, author = {Foord, C and Prjibelski, AD and Hu, W and Michielsen, L and Vandelli, A and Narykov, O and Evans, B and Hsu, J and Belchikov, N and Jarroux, J and He, Y and Ross, ME and Hajirasouliha, I and Tartaglia, GG and Korkin, D and Tomescu, AI and Tilgner, HU}, title = {A spatial long-read approach at near-single-cell resolution reveals developmental regulation of splicing and polyadenylation sites in distinct cortical layers and cell types.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {40661641}, issn = {2692-8205}, support = {R01 GM135247/GM/NIGMS NIH HHS/United States ; R35 GM152101/GM/NIGMS NIH HHS/United States ; U01 DA053625/DA/NIDA NIH HHS/United States ; R01 HD111089/HD/NICHD NIH HHS/United States ; T32 DA039080/DA/NIDA NIH HHS/United States ; RF1 MH121267/MH/NIMH NIH HHS/United States ; R35 GM138152/GM/NIGMS NIH HHS/United States ; R01 LM014017/LM/NLM NIH HHS/United States ; }, abstract = {Genome-wide single-cell and spatial long-read approaches have gained traction, but mostly lack single-cell resolution - and yield limited read lengths. Here, we introduce spatial ISOform sequencing (Spl-ISO-Seq), which reveals exons and polyadenylation sites from long reads with near-single-cell resolution. Spl-ISO-Seq selects long cDNAs and doubles to triples read lengths compared to standard preparations. Adding a highly specific software tool (Spl-ISOquant) and comparing human post-mortem pre-puberty samples of the visual cortex (8-11 years) to post-puberty samples (16-19 years), we find that cortical layers harbor stronger splicing and poly(A)-site regulation than the adjacent white matter, with enrichment of multiple protein-domain types. For oligodendrocytes however, developmental splicing changes are stronger in white matter. Among cortical layers, layer 4 has the most developmental changes in alternative-exon inclusion in excitatory neurons and in poly(A) sites. We also find many repeat elements, especially ERV1 long terminal repeats downstream of developmentally-regulated layer 4 exons. Overall, alternative splicing changes are linked to synapses - specifically at the post-synapse. Age-linked splicing changes in layers 1-3 and 4 are associated with autism spectrum disorder but not with schizophrenia, amyotrophic lateral sclerosis and Alzheimer's disease. These results root developmental splicing changes during puberty and the resulting protein changes in specific layers and cell types. More generally, our new technologies enable new observations for any complex tissue.}, } @article {pmid40661462, year = {2025}, author = {Ye, Y and Zhang, Z and Xiao, Y and Zhu, C and Wright, N and Asbury, J and Huang, Y and Wang, W and Gomez-Isaza, L and Troncoso, JC and He, C and Sun, S}, title = {DCPS modulates TDP-43 mediated neurodegeneration through P-body regulation.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2025.06.13.659508}, pmid = {40661462}, issn = {2692-8205}, abstract = {The proteinopathy of the RNA-binding protein TDP-43, characterized by nuclear clearance and cytoplasmic inclusion, is a hallmark of multiple neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and Alzheimer's disease (AD). Through CRISPR interference (CRISPRi) screening in human neurons, we identified the decapping enzyme scavenger (DCPS) as a novel genetic modifier of TDP-43 loss-of-function (LOF)-mediated neurotoxicity. Our findings reveal that TDP-43 LOF leads to aberrant mRNA degradation, via disrupting the properties and function of processing bodies (P-bodies). TDP-43 interacts with P-body component proteins, potentially influencing their dynamic equilibrium and assembly into ribonucleoprotein (RNP) granules. Reducing DCPS restores P-body integrity and RNA turnover, ultimately improving neuronal survival. Overall, this study highlights a novel role of TDP-43 in RNA processing through P-body regulation and identifies DCPS as a potential therapeutic target for TDP-43 proteinopathy-related neurodegenerative diseases.}, } @article {pmid40661327, year = {2025}, author = {Kawakami, Y and Iguchi, Y and Li, J and Amakusa, Y and Yoshimura, T and Chikuchi, R and Yokoi, S and Iida, M and Riku, Y and Iwasaki, Y and Hirose, T and Nakagawa, S and Katsuno, M}, title = {Downregulation of NEAT1 due to loss of TDP-43 function exacerbates motor neuron degeneration in amyotrophic lateral sclerosis.}, journal = {Brain communications}, volume = {7}, number = {4}, pages = {fcaf261}, pmid = {40661327}, issn = {2632-1297}, abstract = {TAR DNA-binding protein 43 (TDP-43) is of particular interest in the pathogenesis of amyotrophic lateral sclerosis (ALS). It has been speculated that loss of nuclear TDP-43 and its cytoplasmic aggregation contributes to neurodegeneration. Although considerable attention has been paid to RNA metabolism in TDP-43 function, TDP-43 is also known to act as a transcription factor. This study found that the expression of Nuclear-enriched abundant transcript 1 (NEAT1), a long-non-coding RNA, was substantially downregulated in motor neurons with nuclear TDP-43 loss, but upregulated in those with preserved nuclear TDP-43, in the postmortem spinal cords of patients with sporadic ALS. TDP-43 depletion induced Neat1 downregulation in Neuro2a cells, primary cortical neurons, and mouse spinal motor neurons. Furthermore, TDP-43 was found to positively regulate NEAT1 at the transcriptional level. Finally, Neat1 knockout exacerbates neurodegeneration of hSOD1[G93A] mice accompanied by increased misfolded superoxide dismutase 1 (SOD1) aggregations. Transcriptome analysis revealed that Neat1 knockout reduced protein folding-related genes, such as heat shock protein family A member 1A (Hspa1a), in the spinal cords of hSOD1[G93A] mice. Our results indicated that the loss of TDP-43 function enhances ALS neurodegeneration by losing the protective effect of NEAT1.}, } @article {pmid40661315, year = {2025}, author = {Anjum, F and Bakhuraysah, M and Alsharif, A and Mohammad, T and Shamsi, A and Hassan, MI}, title = {Emerging biomarkers in amyotrophic lateral sclerosis: from pathogenesis to clinical applications.}, journal = {Frontiers in molecular biosciences}, volume = {12}, number = {}, pages = {1608853}, pmid = {40661315}, issn = {2296-889X}, abstract = {Amyotrophic lateral sclerosis (ALS) is a severe neurodegenerative condition marked by the gradual loss of motor neurons in the brain and spinal cord. As the most common adult-onset motor neuron disease, ALS manifests through gradually worsening muscle weakness that ultimately progresses to complete paralysis. The disease presents in both sporadic and familial forms. Diagnosis is often delayed until substantial and irreversible motor neuron damage has already occurred. Clinical outcomes in ALS have only been defined through large-scale clinical trials with lengthy follow-up periods due to the disease's inherent heterogeneity and the absence of disease-specific biomarkers. Current biomarker detection methods, such as invasive cerebrospinal fluid (CSF) analysis or advanced imaging, are impractical for routine use, particularly in late-stage ALS. Several blood-based biomarkers have shown promise, including neurofilament levels, cryptic RNA-derived peptides, and immune-mediated changes, which may enable non-invasive monitoring. Nevertheless, the development of these methods is hindered by technical challenges, such as blood matrix interference and low analyte abundance. Among the emerging biomarkers, neurofilament light chain (NfL) appears to be the most promising, as its concentrations change in line with disease progression and distinguish clinically relevant groups. NfL facilitates patient stratification based on clinical progression rates (e.g., rapid vs slow progressors), while cryptic exon-derived peptides, such as UNC13A-derived peptides, enable genetic stratification by identifying molecular subtypes linked to TDP-43 pathology (e.g., C9orf72 vs sporadic ALS). These biomarkers hold promise to optimize clinical trial design through enriched cohort selection and accelerating therapeutic translation by monitoring target engagement. In this review, we have summarized recent developments in ALS biomarker studies, focusing on neurofilaments in each biofluid, transcriptomic signatures, and neuroinflammatory biomarkers, emphasizing technical challenges surrounding reproducibility in measurement. Finally, we discussed the potential integration of these biomarkers into clinical practice to advance drug development through precision medicine, thereby enabling shorter and more targeted clinical trials.}, } @article {pmid40661236, year = {2025}, author = {López-Royo, T and Moreno-Martínez, L and Rada, G and Macías-Redondo, S and Calvo, AC and García-Redondo, A and Manzano, R and Osta, R}, title = {LncRNA levels in the central nervous system as novel potential players and biomarkers in amyotrophic lateral sclerosis.}, journal = {Non-coding RNA research}, volume = {14}, number = {}, pages = {145-155}, pmid = {40661236}, issn = {2468-0540}, abstract = {Research in amyotrophic lateral sclerosis (ALS) faces major burdens, including the urgent need for sensitive and specific biomarkers, the identification of novel and effective therapeutic targets and a deeper understanding of the mechanisms driving the disease. In this line, long non-coding RNAs (lncRNAs) have emerged as promising candidates due to their regulatory role in a variety of important biological processes such as RNA metabolism, neuroinflammation, apoptosis or proteostasis. This study aims to elucidate the expression profile of 14 lncRNAs in both the SOD1[G93A] mouse model and ALS patients. Different stages of the disease (presymptomatic, symptomatic and terminal) and 3 regions of the central nervous system (CNS) differentially affected by ALS (spinal cord, brainstem and frontal cortex) were included in the experimental design. In SOD1[G93A] mice, all 14 lncRNAs exhibited differential expression patterns influenced by sex, age, and region, except for Malat1, Neat1, and H19, which displayed consistent expression patterns (Malat1 was decreased, while Neat1 and H19 were increased). These patterns were most prominent in the spinal cord, where lncRNAs were overall down-regulated. In contrast, in the brainstem and frontal cortex, lncRNAs were predominantly up-regulated. Notably, Gas5 expression levels in frontal cortex and spinal cord at the terminal stage correlated with the onset and progression of motor coordination and strength decline. Additionally, three lncRNAs (Gas5, Neat1 and Myoparr) were found to significantly correlate with survival. In human ALS samples, increased levels of NEAT1 and SNHG16 were observed in the brainstem, and of MEG3 and H19 in the frontal cortex, whereas MALAT1 levels were decreased in frontal cortex. In conclusion, this work supports lncRNAs as promising candidates as novel players and potential biomarkers in ALS and highlights SOD1[G93A] mice as a good model to study lncRNAs in the CNS in the context of this disease.}, } @article {pmid40660446, year = {2025}, author = {Singh, D}, title = {Mitochondrial Dysfunction in Neurodegenerative Disorders: Role of Prototype Targeted Drug Delivery Solutions.}, journal = {Current drug safety}, volume = {}, number = {}, pages = {}, doi = {10.2174/0115748863375490250626163609}, pmid = {40660446}, issn = {2212-3911}, abstract = {Mitochondrial dysfunction plays a central role in the pathogenesis of neurodegenerative disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and Amyotrophic Lateral Sclerosis (ALS). Targeted drug delivery to mitochondria represents a promising therapeutic strategy to mitigate neuronal degeneration and preserve mitochondrial function in these devastating conditions. This review provides a comprehensive overview of recent advances in targeted drug delivery solutions for mitochondrial dysfunction in neurodegenerative disorders. The mechanisms underlying mitochondrial dysfunction in AD, PD, HD, and ALS are explored, highlighting the specific challenges and opportunities for therapeutic intervention. Emerging drug delivery technologies are discussed, including mitochondriaresponsive systems, nanoparticles, peptides, and viral vectors, designed to deliver therapeutic agents directly to mitochondria along with suitable case studies. Furthermore, preclinical and clinical studies evaluating the efficacy and safety of mitochondria-targeted therapeutics are reviewed, and future directions and challenges in the field are outlined. By elucidating the intersection of mitochondrial biology and drug delivery, this review aims to inspire further research and innovation toward effective treatments for neurodegenerative diseases.}, } @article {pmid40660191, year = {2025}, author = {Schmidt, R and Slotina, E and Meissner, F and Metelmann, M and Ilse, B and Vogt, V and Freytag, A}, title = {Palliative care pathways in Amyotrophic Lateral Sclerosis (ALS): a sequence analysis of health claims data.}, journal = {BMC palliative care}, volume = {24}, number = {1}, pages = {200}, pmid = {40660191}, issn = {1472-684X}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy/psychology ; *Palliative Care/methods/statistics & numerical data/standards ; Male ; Female ; Cross-Sectional Studies ; Retrospective Studies ; Germany ; Aged ; Middle Aged ; Adult ; Insurance Claim Review/statistics & numerical data ; Aged, 80 and over ; *Critical Pathways/statistics & numerical data/standards ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis is a progressive neurodegenerative disease requiring palliative care. Despite the availability of palliative care services, utilization patterns among people with ALS (pALS) remain poorly understood. This study aimed to analyze palliative care utilization (i.e., primary palliative care (PPC), specialized palliative homecare (SPHC), inpatient palliative care, hospice services) in the last year of life among pALS, to identify distinct care pathways using sequence analysis, and examine their association with end-of-life care quality.

METHODS: A retrospective cross-sectional study using German health claims data (2016 - 2019). Sequence analysis with Temporal Needleman-Wunsch alignment and clustering identified pathway clusters based on type, order, and timing of palliative care services. The study included 1,295 pALS who died between 2016 and 2019 and were insured with a large German health insurance provider. Inclusion required an ALS diagnosis without concurrent cancer.

RESULTS: Of 1,295 pALS, 695 (53.7%) received palliative care. Sequence analysis identified nine distinct care pathway clusters. Quality indicators varied highly across clusters. Pathways involving SPHC, either alone, with PPC, and/or with hospice care, showed fewer emergency visits, hospital stays, and in-hospital deaths, suggesting higher end-of-life care quality.

CONCLUSIONS: Palliative care utilization varies substantially in type, order, and timing. Findings suggest that end-of-life care quality depends not only on the provision of palliative care but also on when and on how different services are combined. Future research should examine the role of interdisciplinary collaboration in palliative care pathways and explore preferences and clinical characteristics of pALS to better understand factors influencing end-of-life care quality.}, } @article {pmid40659932, year = {2025}, author = {Castelnovo, V and Canu, E and Basaia, S and Spinelli, EG and Freri, F and Schito, P and Russo, T and Falzone, Y and Verde, F and Torre, S and Poletti, B and Tremolizzo, L and Appollonio, I and Ticozzi, N and Silani, V and Filippi, M and Agosta, F}, title = {Brain functional connectivity changes in amyotrophic lateral sclerosis with apathy and depression.}, journal = {Journal of neurology}, volume = {272}, number = {8}, pages = {509}, pmid = {40659932}, issn = {1432-1459}, support = {StG-2016_714388_NeuroTRACK//H2020 European Research Council/ ; Investment PE8 - Project Age-It: "Ageing Well in an Ageing Society"//Ministero dell'Università e della Ricerca/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnostic imaging/physiopathology/complications/psychology ; *Apathy/physiology ; Male ; Female ; Middle Aged ; *Depression/diagnostic imaging/physiopathology/etiology ; Aged ; *Brain/physiopathology/diagnostic imaging ; Magnetic Resonance Imaging ; Connectome ; Neural Pathways/physiopathology/diagnostic imaging ; }, abstract = {BACKGROUND: Apathy and depression are the most prevalent neuropsychiatric symptoms in amyotrophic lateral sclerosis (ALS). Although insufficiently investigated, their distinction holds important clinical relevance for accurate diagnosis of ALS with behavioural impairment and for patients' prognosis and management. In the present study, we aimed to assess both apathy and depressive symptoms in patients with ALS and whether they have similar or different functional neural correlates.

METHODS: Using graph analysis and connectomics, global and lobar nodal properties and regional functional brain connectivity were assessed in ALS patients without apathy/depression (ALSn, n = 42), with apathy without depression (ALSa, n = 14), with depressive symptoms without apathy (ALSd, n = 20), and with apathy and depressive symptoms (ALSad, n = 6), and 46 healthy controls. Correlations between brain functional properties, apathy and depressive symptoms were performed in all patients.

RESULTS: Depressive symptoms were related with reduced path length within bilateral basal ganglia (BG) network, and apathy was related with increased path length, decreased nodal strength and local efficiency within left BG network. ALSa patients showed altered functional nodal properties within BG network compared to ALSn and ALSd. Compared to healthy controls and all non-apathetic patients (ALSn and ALSd), all apathetic patients (ALSa and ALSad) exhibited altered functional nodal properties within parietal, occipital and frontal networks. Non-apathetic patients, compared to apathetic patients, showed relatively preserved functional nodal properties in the BG network.

CONCLUSIONS: Our findings indicate differences in brain functional neural organization associated with apathy and depression, underscoring the importance of distinguishing these symptoms in ALS and highlighting the need for targeted interventions.}, } @article {pmid40659544, year = {2025}, author = {Stenvall, E and Grönlund, KÅ and Rohan, Z and Zetterström, P and Nordin, A and Forsberg, K}, title = {Pathology of three ALS patients with FUS variants, including one likely benign Q23L variant lacking FUS inclusions.}, journal = {Human molecular genetics}, volume = {}, number = {}, pages = {}, doi = {10.1093/hmg/ddaf119}, pmid = {40659544}, issn = {1460-2083}, support = {FO2023-0088//Swedish Brain Foundation/ ; FO2024-0232//Swedish Brain Foundation/ ; //Börje Salming ALS Foundation/ ; 2023.10//Ulla-Carin Lindquist Foundation/ ; 2023.16//Ulla-Carin Lindquist Foundation/ ; //Neuroförbundet Association/ ; RV-1005785//Västerbotten County Council/ ; RV-1013622//Västerbotten County Council/ ; RV-993493//Västerbotten County Council/ ; RV-996234//Västerbotten County Council/ ; RV-1014212//Västerbotten County Council/ ; RV-996140//Västerbotten County Council/ ; }, abstract = {Fused in sarcoma (FUS) is an RNA-binding protein implicated in juvenile amyotrophic lateral sclerosis (ALS). Mutations in the FUS gene, particularly those affecting the nuclear localization signal (NLS), impair nuclear import and lead to cytoplasmic accumulation of FUS inclusions in motor neurons. However, the pathological and clinical significance of FUS variants outside the NLS remains less understood. Here, we describe clinical and histopathological findings from three ALS patients carrying FUS variants: two with NLS-region variants (R495X and P525L), and one with a variant in the N-terminal region outside the NLS (Q23L). The patients carrying NLS variants presented with aggressive, juvenile-onset spinal and bulbar ALS, characterized primarily by lower motor neuron involvement and rapid disease progression. In contrast, the Q23L patient exhibited a slowly progressive disease course, with predominantly upper motor neuron signs. Neuropathological analysis revealed cytoplasmic FUS inclusions in motor neurons of patients with NLS variants, consistent with typical FUS pathology. In contrast, the Q23L patient lacked FUS inclusions and instead displayed pTDP-43 pathology in the hippocampus, neocortex (including the motor cortex), nucleus olivaris, lentiform nucleus, striatum, and some lower motor neurons. Taken together, these results suggest that Q23L is most likely a benign variant. As antisense oligonucleotides (ASOs) targeting FUS are currently being explored in clinical trials, further neuropathological investigations are needed to determine whether ASO-mediated FUS silencing would be effective for patients carrying FUS variants outside the NLS region.}, } @article {pmid40659018, year = {2025}, author = {Yang, EJ}, title = {Combined herbal medicine (A. bidentata, G. elata, and C. sinensis) increases anti-inflammatory and anti-oxidative effects in a mouse model of amyotrophic lateral sclerosis.}, journal = {Pharmacology}, volume = {}, number = {}, pages = {1-21}, doi = {10.1159/000547388}, pmid = {40659018}, issn = {1423-0313}, abstract = {INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease caused by the loss of motor neurons, finally leading to death by respiratory failure. However, no effective drug is available for treating patients with ALS owing to the complex pathological mechanisms. Herbal medicines are globally known for the effects of their multiple bioactive components and lack of adverse effects.

OBJECTIVE: This study investigated the effects of a combined herbal medicine formulation containing Achyranthes bidentata Blume, Gastrodia elata Blume, and Chaenomeles sinensis Koehne extracts on motor function and to analyze the underlying biological mechanisms in the gastrocnemius and tibia anterior muscles and spinal cord of hSOD1G93A mice.

METHODS: Rotarod and footprint analyses were performed to examine motor function. The biological mechanisms were examined using western blot and immunohistochemistry analyses of the muscles and spinal cord in hSOD1G93A mice.

RESULTS: Herbal medicine treatment improved motor function in hSOD1G93A mice by reducing the expression of inflammation-related proteins (glial fibrillary acidic protein and CD11b) and oxidative stress-related proteins (heme oxygenase 1 and ferritin) in the gastrocnemius and tibia anterior muscles and spinal cord. It also regulated autophagy in the muscles and spinal cord of hSOD1G93A mice.

CONCLUSIONS: Collectively, these findings suggest that the herbal medicine formulation reported herein may facilitate management of diseases with complex pathological mechanisms, such as ALS, or those with unclear pathological mechanisms.}, } @article {pmid40658257, year = {2025}, author = {Fasano, A and Vacchiano, V and Bonan, L and McMackin, R and Nasseroleslami, B and Hardiman, O and Liguori, R}, title = {Neurophysiological biomarkers of networks impairment in amyotrophic lateral sclerosis.}, journal = {Journal of neurology}, volume = {272}, number = {8}, pages = {507}, pmid = {40658257}, issn = {1432-1459}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology/diagnosis ; Biomarkers ; Transcranial Magnetic Stimulation ; *Nerve Net/physiopathology ; Electroencephalography ; Electromyography ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a heterogeneous disease involving motor system as well as cognitive domains. There is an urgent need for objective biomarkers that can subcategorize subjects into homogeneous groups based on disease pathobiology.In this review, we discuss novel neurophysiological techniques that provide detailed, multiscale and multidimensional insights into ALS networks impairment, spanning from the micro-columnar architecture of the motor cortex to motor and cognitive networks. Specifically, Transcranial Magnetic Stimulation (TMS) paradigms can be used to evaluate the status of excitatory and inhibitory networks within the layers of the motor cortex. Abnormalities in functional connectivity between the two motor areas, as well as within the frontal-temporal and frontal parietal networks, can be characterized using novel source-localization analysis of high-density electroencephalography (EEG). TMS and EEG techniques provide data that correlate with both motor and cognitive impairment. Furthermore, cortico-muscular coherence analysis can be used to assess functional dysregulation within the entire motor system, and novel surface electromyography (EMG) techniques, such as motor unit number estimation, motor unit number index, and nerve excitability testing studies provide useful insights into axonal loss and membrane ion channel dysfunctions in lower motor neurons.The integrated analysis of these biomarkers provides valuable insights into the clinical and biologic heterogeneity of the disease, aiding the intelligent design of next generation precision-based therapeutics.}, } @article {pmid40655414, year = {2025}, author = {Thiry, L and Sirois, J and Durcan, TM and Stifani, S}, title = {Derivation and Culture of Enriched Phrenic-Like Motor Neurons From Human iPSCs.}, journal = {Bio-protocol}, volume = {15}, number = {13}, pages = {e5363}, pmid = {40655414}, issn = {2331-8325}, abstract = {The fatal motor neuron (MN) disease amyotrophic lateral sclerosis (ALS) is characterized by progressive degeneration of the phrenic MNs (phMNs) controlling the activity of the diaphragm, leading to death by respiratory failure. Human experimental models to study phMNs are lacking, hindering the understanding of the mechanisms of phMN degeneration in ALS. Here, we describe a protocol to derive phrenic-like MNs from human induced pluripotent stem cells (hiPSC-phMNs) within 30 days. During spinal cord development, phMNs emerge from specific MN progenitors located in the dorsalmost MN progenitor (pMN) domain at cervical levels, under the control of a ventral-to-dorsal gradient of Sonic hedgehog (SHH) signaling and a rostro-caudal gradient of retinoic acid (RA). The method presented here uses optimized concentrations of RA and the SHH agonist purmorphamine, followed by fluorescence-activated cell sorting (FACS) of the resulting MN progenitor cells (MNPCs) based on a cell-surface protein (IGDCC3) enriched in hiPSC-phMNs. The resulting cultures are highly enriched in MNs expressing typical phMN markers. This protocol enables the generation of hiPSC-phMNs and is highly reproducible using several hiPSC lines, offering a disease-relevant system to study mechanisms of respiratory MN dysfunction. While the protocol has been validated in the context of ALS research, it can be adopted to study human phrenic MNs in other research fields where these neurons are of interest. Key features • This protocol generates enriched hiPSC-derived phrenic motor neuron cultures. • The protocol can be used to develop models to study human respiratory motor neuron disease. • The protocol allows the generation of phrenic motor neuron preparations with potential for motor neuron replacement strategies. • The protocol requires experience in hiPSC culturing and FACS-based cell sorting for a successful outcome.}, } @article {pmid40655294, year = {2025}, author = {Rinofner-Kreidl, S}, title = {Ist das Gegebene noch zu retten? Über Chancen und Gefahren einer Politisierung der Phänomenologie.}, journal = {Husserl studies}, volume = {41}, number = {2}, pages = {267-302}, doi = {10.1007/s10743-025-09363-5}, pmid = {40655294}, issn = {0167-9848}, abstract = {Dieser Essay zielt darauf, eine Mehrdeutigkeit der Rede von "Politisierung" herauszuarbeiten, die sowohl für die Selbstkritik phänomenologischen Denkens als auch für die Kritik der Phänomenologie als eines öffentlichen Diskurses von Bedeutung ist. Die fraglichen Unterschiede betreffen das Verständnis dessen, was infolge einer Politisierung des Denkens anders konzipiert, kontextualisiert oder interpretiert wird, ob eine Politisierung intrinsisch oder extrinsisch motiviert und begründet ist und wie Art und Reichweite der daran geknüpften Ansprüche argumentiert werden können. Zwei Optionen werden erörtert: (1) eine interne Politisierung, die als phänomenologisch-methodischer Umgang mit Gegebenem und als kollektiv praktizierter Evidenzstil charakterisiert wird; (2) eine externe Politisierung, die sich als standort- und kontextabhängige weltanschauliche Idee und Praxis darstellt. Letztere versteht sich als eine politische Forderung und Erwartung, die eine thematisch einseitige bzw. verengte und / oder unreflektierte, unkritische, womöglich vorurteils- und ressentimentgeleitete phänomenologische Untersuchung korrigiert. Es wird argumentiert, dass interne Politisierung auf einer Metaebene stattfindet, auf der über Natur und Selbstbegrenzung der phänomenologischen Analyse nachgedacht wird. In konkreten Phänomenanalysen schlägt sich interne Politisierung lediglich indirekt, über deren methodische und theoretische Rahmung, nieder. Interne Politisierung ist mit autonomer Vernunftausübung verträglich. Dies gilt nicht für jede Form externer Politisierung, die als direkter Eingriff auf der gegenständlichen Ebene, im Zuge der Interpretation konkreter Phänomene, erfolgt. Zu klären ist: Wie können zulässige und eventuell unabdingbare Formen von Politisierung von unzulässigen unterschieden werden? Unter welchen Bedingungen unterliegt die Politisierung des Denkens einem Selbstwiderlegungseinwand?}, } @article {pmid40654997, year = {2025}, author = {Barbieri, EM and Linsenmeier, M and Whiteman, KR and Cheng, Y and Braganza, S and Copley, KE and Miranda-Castrodad, P and Lewis, B and Villafañe, K and Amado, DA and Davidson, BL and Shorter, J}, title = {Scouring the human Hsp70 network uncovers diverse chaperone safeguards buffering TDP-43 toxicity.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {40654997}, issn = {2692-8205}, support = {K99 AG075242/AG/NIA NIH HHS/United States ; T32 GM132039/GM/NIGMS NIH HHS/United States ; F31 NS129101/NS/NINDS NIH HHS/United States ; K08 NS114106/NS/NINDS NIH HHS/United States ; R21 AG065854/AG/NIA NIH HHS/United States ; F32 NS108598/NS/NINDS NIH HHS/United States ; R01 GM099836/GM/NIGMS NIH HHS/United States ; }, abstract = {Cytoplasmic aggregation and concomitant dysfunction of the prion-like, RNA-binding protein TDP-43 underpin several fatal neurodegenerative diseases, including amyotrophic lateral sclerosis. To elucidate endogenous defenses, we systematically scoured the entire human Hsp70 network for buffers of TDP-43 toxicity. We identify 30 J-domain proteins (2 DNAJAs, 10 DNAJBs, 18 DNAJCs), 6 Hsp70s, and 5 nucleotide-exchange factors that mitigate TDP-43 toxicity. Specific chaperones reduce TDP-43 aggregate burden and detoxify diverse synthetic or disease-linked TDP-43 variants. Sequence-activity mapping unveiled unexpected, modular mechanisms of chaperone-mediated protection. Typically, DNAJBs collaborate with Hsp70 to suppress TDP-43 toxicity, whereas DNAJCs act independently. In human cells, specific chaperones increase TDP-43 solubility and enhance viability under proteotoxic stress. Strikingly, spliceosome-associated DNAJC8 and DNAJC17 retain TDP-43 in the nucleus and promote liquid-phase behavior. Thus, we disambiguate a diverse chaperone arsenal embedded in the human proteostasis network that counters TDP-43 toxicity and illuminate mechanistic gateways for therapeutic intervention in TDP-43 proteinopathies.}, } @article {pmid40654973, year = {2025}, author = {Sangwan, S and Rieder, HE and Moore, D and Khanlou, N and Novitch, B and Geisberg, M and Eisenberg, DS}, title = {A structure-guided antibody detects SOD1 oligomers in diverse ALS genotypes.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {40654973}, issn = {2692-8205}, support = {R01 AG029430/AG/NIA NIH HHS/United States ; }, abstract = {Antibodies offer versatility as diagnostic and therapeutic tools to target specific protein epitopes. However, the transient nature of intermediate protein conformations, such as that of amyloid oligomers, poses a challenge for antibody development. We use a structure-guided approach to generate a monoclonal antibody against oligomers of Superoxide Dismutase 1 (SOD1). Mutations in SOD1 are linked to a subset of familial Amyotrophic Lateral Sclerosis (fALS), a fatal neurodegenerative disease. Based on the corkscrew-like features of non-native SOD1 oligomers previously determined, we generate an antibody specific to SOD1 oligomers. We show that the antibody, CSAb detects SOD1 oligomers, not fibrils or native SOD1, and alleviates the cytotoxic effects of SOD1 oligomers in a cell culture model of primary motor neurons. Immunohistochemical analyses of human ALS subjects show CSAb reactivity in both neuronal and non-neuronal cells. Finally, we provide evidence that CSAb reactive SOD1 oligomers are present in non-SOD1 linked fALS and sporadic ALS subjects. Together, our study provides a new probe against SOD1 oligomers and suggests that cytotoxic SOD1 oligomers are prevalent in diverse ALS genotypes.}, } @article {pmid40654957, year = {2025}, author = {Sheth, U and Harrison, R and Ferber, K and Rosenbaugh, EG and Bevis, A and Khillan, R and Benatar, M and Bjorklund, NL and Di Daniel, E and Harris, GA and Kahn, OI and Liu, Y and Zetterberg, H and Mitic, LL and Graham, D and Gendron, TF}, title = {Measuring neurofilament light in human plasma and cerebrospinal fluid: a comparison of five analytical immunoassays.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {40654957}, issn = {2692-8205}, support = {U01 NS107027/NS/NINDS NIH HHS/United States ; U54 NS092091/NS/NINDS NIH HHS/United States ; }, abstract = {OBJECTIVES: Neurofilament light (NfL) is an established biofluid marker of neuroaxonal injury for neurological diseases. Several high-throughput and sensitive immunoassays have been developed to quantify NfL in blood and cerebrospinal fluid (CSF), facilitating the use of NfL as a biomarker in research and clinical practice. However, because of the lack of rigorous comparisons of assays, it has been difficult to determine whether data are comparable and whether assay performance differs. Here, we compared the performance of five NfL immunoassays.

METHODS: To assess the five NfL immunoassays (Fujirebio, ProteinSimple, Quanterix, Roche and Siemens), we used pooled plasma or pooled CSF, as well as unique samples from 20 healthy controls and 20 individuals with El Escorial defined probable or definite amyotrophic lateral sclerosis (ALS), to evaluate precision, parallelism and/or bias. We also examined correlations between plasma and CSF NfL concentrations within and across assays and evaluated their ability to differentiate healthy controls from individuals with ALS.

RESULTS: Four of the five assays demonstrated exemplary performance based on our analyses of precision and parallelism. Across the five assays, NfL concentrations were lower in plasma than in CSF, although they displayed a high degree of correlation. We noted bias across assays; plasma NfL concentrations were lowest for the Roche assay and highest for the ProteinSimple assay. In addition, all assays reliably distinguished healthy controls from individuals with ALS using plasma or CSF NfL.

CONCLUSIONS: Four NfL assays demonstrated similar analytic performance. Alongside performance, other factors such as costs, accessibility, useability, footprint, and intended use, should be considered.}, } @article {pmid40654715, year = {2025}, author = {Van Zuiden, W and Meimoun, TD and Bar, C and Siany, A and Moshe, L and Yacovzada, NS and Weizman, E and Neumann, M and Buchman, AS and Wang, Y and Bennett, DA and Glass, JD and Trautwig, AN and Seyfried, NT and Cooper-Knock, J and Hornstein, E}, title = {TDP-43 toxic gain of function links ALS, FTD and Alzheimer's Disease through splicing dysregulation.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2025.04.20.648873}, pmid = {40654715}, issn = {2692-8205}, abstract = {Loss of nuclear TDP-43 splicing activity is a common feature across neurodegenerative diseases including amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD), but its relevance to Alzheimer's disease (AD) remains unclear. Here, we show that TDP-43 pathology in AD is broadly associated with splicing abnormalities, including aberrant splicing of amyloid precursor protein (APP). TDP-43 drives the formation of elongated APP isoforms, disrupting alternative splicing across ALS, FTLD-TDP and AD, providing a compelling mechanism for a long-standing observation of APP isoform dysregulation. We further establish a mechanistic link between TDP-43, APP splicing, and A-beta pathology. Surprisingly, the disruption to alternative APP splicing is mediated by a toxic gain of cytoplasmic TDP-43 function, rather than loss of its nuclear role. Using proximity proteomics and base editing in human iPSC-derived neurons, we show that TDP-43 pathology causes cytoplasmic co-sequestration of splicing regulators SCAF11, SRSF5, and TIAL1. Knockdown of these regulators also results in APP mis-splicing and increased A-beta burden, without affecting other TDP-43 targets such as STMN2 or UNC13A. Together, our findings suggest that TDP-43-mediated splicing dysfunction upstream of APP contributes to the pathogenesis of seemingly disparate neurodegenerative diseases, uniting AD and ALS/FTLD-TDP through a shared molecular mechanism.}, } @article {pmid40653816, year = {2025}, author = {Bozovic, I and Licina, E and Bjelica, B and Milicevic, O and Palibrk, A and Basta, I and Peric, S and Pavlovic, A and Stevic, Z and Mijajlovic, M}, title = {Transcranial Brain Parenchyma Sonographic Findings in Familial and Sporadic Amyotrophic Lateral Sclerosis.}, journal = {European journal of neurology}, volume = {32}, number = {7}, pages = {e70272}, pmid = {40653816}, issn = {1468-1331}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnostic imaging/genetics/pathology ; Male ; Female ; Middle Aged ; Cross-Sectional Studies ; Aged ; *Ultrasonography, Doppler, Transcranial/methods ; Adult ; *Brain/diagnostic imaging ; *Substantia Nigra/diagnostic imaging ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder affecting motor neurons. Transcranial sonography (TCS) is a valuable tool for assessing deep brain structures. This study aimed to analyze TCS findings in both sporadic (sALS) and familial ALS (fALS) patients and compare them to healthy controls (HC).

METHODS: This cross-sectional study included 278 patients with sALS and 31 patients with genetically confirmed fALS, and 93 age- and gender- matched HC. TCS was used to assess substantia nigra (SN) and brainstem raphe (BR) echogenicity and third ventricle diameter (TVD). Functional disability was evaluated using the ALS Functional Rating Scale-Revised.

RESULTS: BR hypoechogenicity was more frequent in fALS (41.9%) and sALS (37.4%) patients, compared to HC (10.8%) (p < 0.001). Right SN hyperechogenicity was observed in 28.1% of sALS, 16.1% of fALS, and 8.6% of HC (p = 0.004). Left SN hyperechogenicity was found in 33.5% of sALS, 29.0% of fALS, and 4.3% of HC (p = 0.004). SN hyperechogenicity findings on either side were highest in sALS (48.4%) compared to fALS (31.0%) and HC (13.3%) (p < 0.001), with a borderline difference between fALS and sALS (p = 0.08). BR hypoechogenicity and SN hyperechogenicity were more common in male patients. Increased TVD correlated with older age, later disease onset, bulbar onset, and lower MMSE scores.

CONCLUSIONS: TCS is an easily applicable and sensitive diagnostic tool that offers novel insights into several brainstem structures and identify significant differences in their echogenicity between ALS patients and healthy controls, while pointing out similar but not identical patterns of echogenicity in both ALS forms.}, } @article {pmid40653481, year = {2025}, author = {Marabita, M and Marchioretti, C and Aravamudhan, A and Zito, S and Falconieri, A and Zuccaro, E and Andreotti, R and Gambarotto, L and Metti, S and Tonellato, M and Adami, V and Park, KH and Gunthorpe, MJ and Large, CH and Marasco, A and Vianello, S and Rosati, J and Belluzzi, E and Pozzuoli, A and Biz, C and Ruggieri, P and Basso, M and Poletti, A and Alvaro, G and Sorarù, G and Bonaldo, P and Rossetto, O and Pilati, N and Pennuto, M}, title = {Kv3 channel agonist ameliorates the phenotype of a mouse model of amyotrophic lateral sclerosis.}, journal = {Acta neuropathologica communications}, volume = {13}, number = {1}, pages = {153}, pmid = {40653481}, issn = {2051-5960}, mesh = {Animals ; *Amyotrophic Lateral Sclerosis/drug therapy/pathology/metabolism/genetics ; *Shaw Potassium Channels/agonists/metabolism/genetics ; Disease Models, Animal ; Humans ; Mice, Transgenic ; Mice ; Phenotype ; Muscle, Skeletal/metabolism/drug effects/pathology ; Male ; Mice, Inbred C57BL ; Female ; Superoxide Dismutase-1/genetics ; }, abstract = {Voltage-gated potassium channels, Kv3.1, Kv3.2, Kv3.3, and Kv3.4, facilitate rapid repolarization and shape action potentials, which are crucial to maintaining high-frequency firing. Little is known about the expression and function of Kv3 channels in skeletal muscle. We show that these channels are expressed in type IIa/IIx fibers, and their transcript levels progressively increase from postnatal age to adulthood in physiological context. In mature myofibers, the Kv3.1 and Kv3.4 channels are enriched in the muscle triads. The expression of the Kv3 channel is lost upon acute motor unit damage, in mouse models of amyotrophic lateral sclerosis (ALS) and spinal and bulbar muscular atrophy (SBMA), and the skeletal muscle of patients with sporadic ALS. Early treatment of ALS and SBMA mice with AUT00201, a positive allosteric modulator of Kv3 channels, improved the phenotype of ALS mice specifically, suggesting that positive modulation of Kv3 channels is a novel therapeutic option for patients with ALS.}, } @article {pmid40653411, year = {2025}, author = {Wei, Y and Zhang, Y and Yu, D}, title = {Low-dose IL-2 reinvigorates the immunoguardians of neurodegenerative diseases.}, journal = {Trends in immunology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.it.2025.07.004}, pmid = {40653411}, issn = {1471-4981}, abstract = {Amyotrophic lateral sclerosis (ALS) is a life-threatening neurodegenerative disease caused by motor neuron loss. In a recent Phase 2b trial, Bensimon and colleagues report that the addition of low-dose interleukin 2 (LD-IL-2) immunotherapy to standard of care (SOC) shows promise in enhancing immune tolerance and improving survival in individuals with slower disease progression.}, } @article {pmid40652712, year = {2025}, author = {Brüge, A and Ponimaskin, E and Labus, J}, title = {Targeting the serotonergic system in the treatment of neurodegenerative diseases-emerging therapies and unmet challenges.}, journal = {Pharmacological reviews}, volume = {77}, number = {5}, pages = {100071}, doi = {10.1016/j.pharmr.2025.100071}, pmid = {40652712}, issn = {1521-0081}, abstract = {More than 65 million people worldwide experience neurodegenerative diseases, such as Alzheimer disease, frontotemporal dementia, Parkinson disease, and amyotrophic lateral sclerosis. As the risk of developing these diseases increases with age, increasing life expectancy will further accelerate their prevalence. Despite major advances in the understanding of the molecular mechanisms of neurodegeneration, no curative therapy is available to date. Neurodegenerative diseases are known to be associated with alterations in serotonergic neurotransmission, which might critically contribute to the pathogenesis of these diseases. Therefore, targeting the serotonergic system appears to be a promising therapeutic approach. In this review, we provide a comprehensive overview of pathological changes in serotonergic neurotransmission in different neurodegenerative diseases and discuss novel treatment strategies based on targeted modulation of the serotonergic system. We primarily focus on the therapeutic approaches modulating serotonin homeostasis, its biosynthesis, and the modulation of defined serotonin receptors. SIGNIFICANCE STATEMENT: A common feature of multiple neurodegenerative diseases is dysregulation of the serotonergic system at the cellular, molecular, and genetic levels that strongly contributes to specific pathological phenotypes. Targeting these alterations represents a suitable therapeutic strategy to combat disease-relevant pathomechanisms, slow down disease progression, and overcome pathological consequences.}, } @article {pmid40651399, year = {2025}, author = {Ma, Y and Wu, S and Liu, H and Ren, C and Xie, Y and Deng, G and Yao, S and Wang, X and Qin, C}, title = {Sodium lignosulfonate alkylates based-biosurfactants for efficient remediation of oily sludge.}, journal = {Journal of environmental management}, volume = {391}, number = {}, pages = {126553}, doi = {10.1016/j.jenvman.2025.126553}, pmid = {40651399}, issn = {1095-8630}, mesh = {*Sewage/chemistry ; *Surface-Active Agents/chemistry ; *Lignin/analogs & derivatives/chemistry ; Spectroscopy, Fourier Transform Infrared ; Biosurfactants ; }, abstract = {An alkylated sodium lignosulphonate (ALS) was prepared for highly efficient thermal washing treatment of oily sludge. The ALS was characterized for their chemical structure and surface activity. Furthermore, ALS was used as a thermal cleaning agent to treat oily sludge under different conditions to obtain an optimal thermal washing process. Finally, the oily sludge before and after thermal washing were characterized to explore its structural and compositional changes. Results obtained from the Fourier Transform Infrared spectroscopy (FT-IR) and Two-dimensional Heteronuclear Single Quantum Coherence(2D-HSQC) confirmed the successful grafting of fatty acid chains(C12) onto the LS molecules. ALS was an ideal surfactant with suitable HLB value and excellent surface tension reduction, foaming and emulsification properties. The optimum thermal washing process for oily sludge was: thermal washing temperature 30 °C, ALS concentration 1.5 g/L.}, } @article {pmid40651326, year = {2025}, author = {Yang, S and Ma, Y and Fu, H and Wang, C and Zhang, Y}, title = {Association between allostatic load and trouble sleeping in U.S. adults.}, journal = {Journal of psychosomatic research}, volume = {196}, number = {}, pages = {112206}, doi = {10.1016/j.jpsychores.2025.112206}, pmid = {40651326}, issn = {1879-1360}, abstract = {OBJECTIVE: This study examined the association between allostatic load and trouble sleeping and assessed whether this relationship varies based on allostatic load score (ALS) criteria.

METHODS: This cross-sectional survey utilized nationally representative data from the National Health and Nutrition Examination Survey (NHANES). ALS was derived using empirical and clinical criteria based on eight biomarkers reflecting cardiovascular, metabolic, and immune function. Weighted multivariate logistic regression was employed to analyze the association between ALS and trouble sleeping, with subgroup analyses conducted to assess gender-specific differences.

RESULTS: Of 5331 participants included in this study, 1485 (29 %) reported trouble sleeping. In multivariate-adjusted logistic regression, higher ALS was associated with increased odds of trouble sleeping (empirical ALS: OR 1.13 [95 % CI 1.07-1.18]; clinical ALS: OR 1.08 [95 % CI 1.04-1.13]). Subgroup analyses confirmed the consistency of this association across genders.

CONCLUSION: This study provides robust evidence of a significant association between ALS and trouble sleeping, supported by observed OR of 1.13 (empirical) and 1.08 (clinical). The consistency of findings across both empirical and clinical ALS underscores the potential role of physiological dysregulation in sleep health, highlighting the need for integrated approaches to stress and sleep management.}, } @article {pmid40651187, year = {2025}, author = {Chang, J and Teo, AH and Shaw, TB and Dupuis, L and Ngo, ST and Steyn, FJ}, title = {Deciphering hypothalamic pathology in ALS: insights into non-motor symptoms and disease progression.}, journal = {EBioMedicine}, volume = {118}, number = {}, pages = {105845}, pmid = {40651187}, issn = {2352-3964}, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with highly heterogeneous clinical presentations. Among the non-motor features increasingly recognised as clinically relevant is the dysregulation of energy balance, with weight loss-particularly due to fat mass loss-emerging as a significant modifier of disease risk, progression, and survival. In this context, the hypothalamus-a key regulator of homeostatic and metabolic processes-has gained attention for its potential role in ALS pathophysiology. This Review synthesises emerging evidence of hypothalamic involvement in ALS, including neuronal loss, proteinopathy, and volume loss observed through histological and neuroimaging studies. We critically examine current imaging approaches and their technical limitations and explore neuroendocrine dysfunction across the hypothalamic-pituitary axes. Collectively, these findings suggest that hypothalamic dysfunction may contribute to clinically relevant metabolic, sleep, behavioural, and cognitive changes in ALS, adding to our understanding of ALS as a multisystem disease. Continued investigation of the hypothalamus may reveal novel biomarkers, inform risk stratification, and identify therapeutic opportunities to address disease heterogeneity and improve clinical outcomes.}, } @article {pmid40650266, year = {2025}, author = {Bashar, MA and Dash, N and Mitra, S and Dash, R}, title = {Disclosing Pathogenic Variant Effects on the Structural Dynamics of the VAPB MSP Domain Causing Familial ALS.}, journal = {International journal of molecular sciences}, volume = {26}, number = {13}, pages = {}, pmid = {40650266}, issn = {1422-0067}, mesh = {*Amyotrophic Lateral Sclerosis/genetics/metabolism ; Humans ; Molecular Dynamics Simulation ; *Vesicular Transport Proteins/genetics/chemistry/metabolism ; Protein Domains ; Mutation ; Protein Structure, Secondary ; Protein Binding ; }, abstract = {Vesicle-associated membrane protein (VAMP)-associated protein B (VAPB) serves as a tethering factor that interacts with various proteins and recruits these proteins to the ER surface, exerting multiple functions, such as organelle membrane tethering, lipid transfer between organelles, regulation of calcium homeostasis, autophagy, and the unfolded protein response (UPR). Its interaction is often mediated by its MSP (major sperm) domain, which binds with FFAT (two phenylalanines in an acidic tract)-motif-containing proteins. However, pathogenic variations, such as P56S, P56H, and T46I, in the VAPB MSP domain lead to the familial form of amyotrophic lateral sclerosis (ALS8). Still, the underlying pathophysiology of ALS8 due to pathogenic variations in the VAPB MSP domain remains elusive. In this study, we conducted molecular dynamics (MD) simulations to understand the pathogenic-variant-derived changes in the structural dynamics of the VAPB MSP domain. We found that pathogenic variants altered the fluctuations and conformational dynamics of the VAPB protein. Analyzing the organizations of the secondary structure revealed that pathogenic variants changed the composition of secondary structure elements, especially increasing the proportion of α-helix while reducing β-sheet formation, which might affect the organelle tethering and other functions of VAPB, as well as VAPB homodimer and heterodimer formation. Taken together, these findings can be further investigated through in vivo and/or in vitro studies to not only clarify the pathophysiology of ALS8 resulting from VAPB MSP domain pathogenic variants but also develop novel therapeutics for the disease that restore the native structural organizations as well as fluctuations and motions.}, } @article {pmid40650046, year = {2025}, author = {Cattaneo, M and Giagnorio, E and Lauria, G and Marcuzzo, S}, title = {Therapeutic Approaches for C9ORF72-Related ALS: Current Strategies and Future Horizons.}, journal = {International journal of molecular sciences}, volume = {26}, number = {13}, pages = {}, pmid = {40650046}, issn = {1422-0067}, support = {//Italian Ministry of Health (RRC)/ ; T4-AN-09 prog. ZRPOS2//CALabria HUB per Ricerca Innovativa ed Avanzata- CALHUB.RIA "Creazione di Hub delle Sci-enze della Vita"/ ; prog. ZRA124//AriSLA foundation, "Bulb-Omics"/ ; PNRR-MCNT2-2023-12377336//the European Union - Next Generation EU - NRRP M6C2 - Investment 2.1 Enhancement and strengthening of biomedical research in the NHS,/ ; }, mesh = {Humans ; *C9orf72 Protein/genetics/metabolism ; *Amyotrophic Lateral Sclerosis/genetics/therapy/metabolism/pathology ; Animals ; DNA Repeat Expansion ; Gene Editing ; Genetic Therapy/methods ; Mutation ; Oligonucleotides, Antisense/therapeutic use ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the loss of upper and lower motor neurons. One of its major genetic causes is C9ORF72, where mutations lead to hexanucleotide repeat expansions in the C9ORF72 gene. These expansions drive disease progression through mechanisms, including the formation of toxic RNAs and the accumulation of damaged proteins such as dipeptide repeats (DPRs). This review highlights these pathogenic mechanisms, focusing on RNA foci formation and the accumulation of toxic DPRs, which contribute to neuronal damage. It also discusses promising targeted therapies, including small molecules and biological drugs, designed to counteract these specific molecular events. Small molecules such as G-quadruplex stabilizers, proteasome and autophagy modulators, and RNase-targeting chimeras show potential in reducing RNA foci and DPR accumulation. Furthermore, targeting enzymes involved in repeat-associated non-AUG (RAN) translation and nucleocytoplasmic transport, which are crucial for disease pathogenesis, opens new therapeutic avenues. Even some anti-viral drugs show encouraging results in preclinical studies. Biological drugs, such as antisense oligonucleotides and gene-editing technologies like CRISPR-Cas, were explored for their potential to specifically target C9ORF72 mutations and modify the disease's molecular foundations. While preclinical and early clinical data show promise, challenges remain in optimizing delivery methods, ensuring long-term safety, and improving efficacy. This review concludes by emphasizing the importance of continued research and the potential for these therapies to alter the disease trajectory and improve patient outcomes.}, } @article {pmid40649976, year = {2025}, author = {Jiménez-García, AM and Tortorella, ME and Nishimura, AL and Arias, N}, title = {The Differential Effects of Genetic Mutations in ALS and FTD Genes on Behavioural and Cognitive Changes: A Systematic Review and Meta-Analysis.}, journal = {International journal of molecular sciences}, volume = {26}, number = {13}, pages = {}, pmid = {40649976}, issn = {1422-0067}, support = {PID2023-151715OB-IOO//Ministry of Science and Innovation/ ; PLEC2022-009464//European Union NextGeneration EU/PRTR/ ; CPP2022-009646//European Union NextGeneration EU/PRTR/ ; }, mesh = {Humans ; *Frontotemporal Dementia/genetics/psychology ; *Amyotrophic Lateral Sclerosis/genetics/psychology ; *Mutation ; *Cognition ; tau Proteins/genetics ; C9orf72 Protein/genetics ; Progranulins/genetics ; Superoxide Dismutase-1/genetics ; Endosomal Sorting Complexes Required for Transport/genetics ; RNA-Binding Protein FUS/genetics ; }, abstract = {Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are linked by shared genetic mutations and overlapping clinical features, forming a clinical spectrum. This systematic review and meta-analysis analysed 97 studies, including 3212 patients with key ALS/FTD gene mutations, to identify gene-specific behavioural profiles. Chromosome 9 open reading frame 72 (C9orf72) mutations were strongly associated with psychotic symptoms and aggression, while superoxide dismutase 1 (SOD1) mutations had minimal cognitive effects. Progranulin (PGRN) mutations correlated with apathy and hallucinations, microtubule-associated protein tau (MAPT) mutations with disinhibition, and charged multivesicular body protein 2B (CHMP2B) with social impairments. Fused in sarcoma (FUS) mutations caused early sleep disturbances, TANK-binding kinase 1 (TBK1) led to disinhibition, and presenilin 1 and 2 (PSEN1/2) was linked to severe aggression. Prodromal cognitive changes in PGRN, MAPT, and CHMP2B mutations suggested early disease onset. Despite overlapping symptoms and clinical heterogeneity, understanding gene-specific patterns could inform tailored care strategies to enhance the quality of life for ALS and FTD patients. This study calls for refined guidelines integrating genetic behavioural profiles to improve patient and family support.}, } @article {pmid40649921, year = {2025}, author = {Neumann, S and Heumann, R}, title = {Is the Voltage-Dependent Anion Channel a Major Player in Neurodegenerative Diseases?.}, journal = {International journal of molecular sciences}, volume = {26}, number = {13}, pages = {}, pmid = {40649921}, issn = {1422-0067}, mesh = {Humans ; *Neurodegenerative Diseases/metabolism/pathology ; *Voltage-Dependent Anion Channels/metabolism/genetics ; Animals ; Mitochondria/metabolism ; }, abstract = {The family of voltage-dependent anion channels (VDACs) comprises three isoforms (VDAC-1, VDAC-2, VDAC-3). VDACs have been extensively described as localised in the outer mitochondrial membrane where they are involved in the exchange of ions, metabolites, and ATP/ADP between mitochondria and cytosol. The VDAC interacts with disease-specific proteins and thus regulates the mitochondrial function and controls the cellular energy resources, explaining its involvement in cell death and apoptosis. In addition, VDAC-1 and -2 can also be found at other cellular locations such as in the sarcoplasmic reticulum, in the endoplasmic reticulum, as well as in the plasma membrane. Through single-channel pore regulation, oligomerisation, or changed expression levels the VDAC is involved in different neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, Amyotrophic lateral sclerosis, Huntington's disease, and others. Here, we critically summarise current discussions about the VDAC as a common key player for these diseases. We suggest that the VDAC acts as a transmembrane multifunctional regulatory protein which might serve as a pharmacological target for the development of novel drugs against neurodegenerative diseases such as the application of recombinant antibody technology.}, } @article {pmid40649859, year = {2025}, author = {Tomczak, J and Kapsa, A and Boczek, T}, title = {Adenylyl Cyclases as Therapeutic Targets in Neuroregeneration.}, journal = {International journal of molecular sciences}, volume = {26}, number = {13}, pages = {}, pmid = {40649859}, issn = {1422-0067}, support = {2020/39/D/NZ4/01250//National Science Center/ ; }, mesh = {Humans ; *Adenylyl Cyclases/metabolism ; Animals ; *Nerve Regeneration/drug effects ; Signal Transduction/drug effects ; Cyclic AMP/metabolism ; *Neurodegenerative Diseases/drug therapy/metabolism ; Neuronal Plasticity ; }, abstract = {Adenylyl cyclases (ACs) are key regulators of cyclic adenosine monophosphate (cAMP) signaling-a pathway critical for neuroregeneration, synaptic plasticity, and neuronal survival. In both the central and peripheral nervous systems, injury-induced activation of ACs promotes axonal outgrowth and functional recovery through the stimulation of protein kinase A (PKA), exchange proteins directly activated by cAMP (Epac), and cAMP-response element-binding protein (CREB). Among the various AC isoforms, calcium-sensitive AC1, AC8, and AC5, as well as bicarbonate-responsive soluble AC (sAC), have emerged as crucial mediators of neuroplasticity and axon regeneration. These isoforms coordinate diverse cellular responses-including gene transcription, cytoskeletal remodeling, and neurotransmitter release-to metabolic, synaptic, and injury-related signals. Dysregulation of AC activity has been implicated in the pathophysiology of neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease, and amyotrophic lateral sclerosis, as well as in chronic pain syndromes. Pharmacological modulation of cAMP levels through AC activation, phosphodiesterase (PDE) inhibition, or pituitary adenylyl cyclase-activating polypeptide (PACAP) receptor signaling has shown therapeutic promise in preclinical models by enhancing neurogenesis, remyelination, and synaptic repair. Conversely, targeted inhibition of specific AC isoforms, particularly AC1, has demonstrated efficacy in reducing maladaptive plasticity and neuropathic pain. This review highlights the diverse roles of ACs in neuronal function and injury response and discusses emerging strategies for their therapeutic targeting.}, } @article {pmid40648447, year = {2025}, author = {Lovrinčević, M and Papa, I and Janeš, D and Hodak, L and Pentek, T and Đuka, A}, title = {New Possibilities of Field Data Survey in Forest Road Design.}, journal = {Sensors (Basel, Switzerland)}, volume = {25}, number = {13}, pages = {}, pmid = {40648447}, issn = {1424-8220}, support = {HRZZ-UIP-2019-04-7766//Croatian Science Foundation/ ; }, abstract = {Field data, as the basis for planning and designing forest roads, must have high spatial accuracy. Classical (using a theodolite and a level) and modern (based on total stations and GNSSs) surveying methods are used in current field data survey for forest road design. This study analyzed the spatial accuracy of classical and modern surveying methods, the accuracy of spatial data recorded using a UAV equipped with an RGB camera at different flight altitudes, and the accuracy of lidar data of the Republic of Croatia. This study was conducted on a forest area where salvage logging was carried out, which enabled the use of a GNSS receiver in RTK mode as a reference method. The highest RMSE values of the spatial coordinates were recorded for measurements obtained with the classical surveying method (0.89 m) and a total station (0.33 m). The flight altitude of the UAV did not significantly affect the spatial error of the collected data, which ranged between 0.07 and 0.09 m. The cross-terrain slope, as one of the factors that significantly affect the amount of earthworks, did not differ statistically significantly between the methods. The ALS error was strongly influenced by the cross-terrain slope. The authors conclude that the new survey methods (SfM and lidar data) provide high-accuracy data but also draw attention to challenges in their use, such as vegetation and biomass on the ground.}, } @article {pmid40646945, year = {2025}, author = {Davì, F and Iaconis, A and Cordaro, M and Di Paola, R and Fusco, R}, title = {Nutraceutical Strategies for Targeting Mitochondrial Dysfunction in Neurodegenerative Diseases.}, journal = {Foods (Basel, Switzerland)}, volume = {14}, number = {13}, pages = {}, pmid = {40646945}, issn = {2304-8158}, abstract = {In neurons, mitochondria generate energy through ATP production, thereby sustaining the high energy demands of the central nervous system (CNS). Mitochondrial dysfunction within the CNS was implicated in the pathogenesis and progression of neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and multiple sclerosis, often involving altered mitochondrial dynamics like fragmentation and functional impairment. Accordingly, mitochondrial targeting represents an alternative therapeutic strategy for the treatment of these disorders. Current standard drug treatments present limitations due to adverse effects associated with their chronic use. Therefore, in recent years, nutraceuticals, natural compounds exhibiting diverse biological activities, have garnered significant attention for their potential to treat these diseases. It has been shown that these compounds represent safe and easily available sources for the development of innovative therapeutics, and by modulating mitochondrial function, nutraceuticals offer a promising approach to address neurodegenerative pathologies. We referred to approximately 200 articles published between 2020 and 2025, identified through a focused search across PubMed, Google Scholar, and Scopus using keywords such as "nutraceutical," "mitochondrial dysfunction," and "neurodegenerative diseases. The purpose of this review is to examine how mitochondrial dysfunction contributes to the genesis and progression of neurodegenerative diseases. Also, we discuss recent advances in mitochondrial targeting using nutraceuticals, focusing on their mechanisms of action related to mitochondrial biogenesis, fusion, fission, bioenergetics, oxidative stress, calcium homeostasis, membrane potential, and mitochondrial DNA stability.}, } @article {pmid40644419, year = {2025}, author = {Bertran-Recasens, B and Vidal-Notari, S and Hernández Guillamet, G and López Seguí, F and Vidal-Alaball, J and Jiménez-Balado, J and Rubio, MA}, title = {Epidemiology of amyotrophic lateral sclerosis: a population-based analysis, 2015-2020.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {}, number = {}, pages = {1-10}, doi = {10.1080/21678421.2025.2527887}, pmid = {40644419}, issn = {2167-9223}, abstract = {Background: Epidemiological data on amyotrophic lateral sclerosis (ALS) in Spain have primarily been derived from small cohort studies, with limited information on survival and comorbidities. This study presents a 10-year follow-up of a large, well-phenotyped community-dwelling ALS cohort in Catalonia, Spain. Methods: This observational study utilized data from the Information System for the Development of Research in Primary Care (SIDIAP), which includes health records for 6,301,095 individuals from 2015 to 2020. We assessed ALS incidence, prevalence, comorbidities, territorial distribution, mortality, and survival times. Results: From 2015 to 2020, 1173 ALS cases were identified, with a median age at diagnosis of 68 years, and 50.4% of cases were female. Incidence and prevalence were estimated at 2.39 per 100,000 person-years and 7.98 cases per 100,000 persons. Dementia was present in 6.8% of cases before ALS diagnosis, while depression and/or anxiety affected 45.7%. Median survival from diagnosis was 2.19 years. Multivariate analysis identified older age at diagnosis (HR: 1.04, 95% CI: 1.04-1.05, p value < 0.001), alcohol abuse (HR: 1.56, 95% CI: 1.04-2.56, p value = 0.017), history of stroke (HR: 1.47, 95% CI: 1.07-2.04, p = 0.006), and dementia (HR: 1.57, 95% CI: 1.18-2.12, p value = 0.001) as independent predictors of mortality. Conclusions: ALS incidence and prevalence in Catalonia are higher than previously estimated for Spain and align closely with rates observed in other Western countries. Older age at diagnosis, alcohol abuse, stroke history, and dementia were all significantly associated with reduced survival. These findings underscore important risk factors affecting prognosis, offering valuable insights into ALS progression.}, } @article {pmid40644388, year = {2025}, author = {Holanda Braga, CAO and Diniz, DS}, title = {Characterizing changes in functioning in Brazilian patients with ALS using a comprehensive ICF core set.}, journal = {Disability and rehabilitation}, volume = {}, number = {}, pages = {1-8}, doi = {10.1080/09638288.2025.2532124}, pmid = {40644388}, issn = {1464-5165}, abstract = {PURPOSE: To longitudinally describe the impact of amyotrophic lateral sclerosis (ALS) using a core set based on the International Classification of Functioning, Disability and Health (ICF).

PATIENTS AND METHODS: Between May 2021 and August 2022, 42 Brazilian patients with ALS (21 men/21 women, mean age 59.92 years, 23.8% with bulbar-onset ALS and 76.2% with spinal-onset ALS) were included. Patients diagnosed at least 6 months previously were assessed using 42 ICF categories at baseline and every six months thereafter for 16 months. The Friedman test was used to compare three time points, followed by Wilcoxon post hoc analyses. The Bonferroni method was applied. P-values ≤0.05 were considered significant. Overall and subgroup (bulbar-onset/spinal-onset ALS) analyses were performed.

RESULTS: Significant changes were found in 24/42 ICF categories. The most affected Body Functions included respiratory muscle functions (b445), power of muscles of one limb (b7301), muscle power (b730) and gait pattern (b770). Early disabilities involved pain sensation (b280) and respiratory functions. Limitations in Activities and Participation included transferring oneself (d420), hand and arm use (d445), dressing (d540), washing oneself (d510) and speaking (d330).

CONCLUSION: This ICF core set may help determine key facilitators and barriers to functioning and disability in ALS, guiding rehabilitation efforts.}, } @article {pmid40643880, year = {2025}, author = {Wang, P and Shang, H and Li, C}, title = {Association of creatinine level with neurodegenerative disorders: a prospective cohort study and Mendelian randomization analysis.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {}, number = {}, pages = {}, pmid = {40643880}, issn = {1590-3478}, support = {24NSFSC0358//Sichuan Science and Technology Program/ ; }, abstract = {BACKGROUND: Multiple evidence has suggested interaction between neurodegenerative disorders (NDDs) and creatinine, a metabolite derived from the high-energy product creatine. However, findings across studies have shown inconsistency, and the effect direction remains controversial. Here, we aimed to explore the link between creatinine and the risk of NDDs.

METHODS: Utilizing data from the UK Biobank, we investigated the association between baseline serum and urine creatinine and the risk of common NDDs using Cox proportional hazards regression analysis. Furthermore, we performed genetic correlation and Mendelian randomization analyses based on summary statistics from genome-wide association studies.

RESULTS: A higher level of serum creatinine at baseline was associated with a lower risk of incident amyotrophic lateral sclerosis (ALS) (beta=-0.013, SE = 0.004, P = 1.88E-03). From the genetic perspective, a significant and negative genetic correlation was identified between serum creatinine and ALS risk (genetic correlation: -0.17, P = 0.017). Mendelian randomization analysis corroborated the primary finding, indicating that serum creatinine was associated with a reduced risk of ALS (OR: 0.92, 95% CI: 0.86-0.98, P = 0.01). Moreover, a higher level of baseline serum creatinine was associated with a reduced risk of incident Alzheimer's disease (beta=-4.89E-03, SE = 2.24E-03, P = 0.03), though the effect size was small.

CONCLUSIONS: These findings enhance our understanding of creatinine's role in the risk of NDDS, suggest the potential of targeting creatinine as a biomarker of ALS, and hold implications for designing therapeutic interventions in clinical trials.}, } @article {pmid40643479, year = {2025}, author = {Sgromo, C and Tosi, M and Olgasi, C and De Marchi, F and Favero, F and Venturin, G and Piola, B and Cucci, A and Corrado, L and Mazzini, L and D'Alfonso, S and Follenzi, A}, title = {Identification of Transcriptomic Differences in Induced Pluripotent Stem Cells and Neural Progenitors from Amyotrophic Lateral Sclerosis Patients Carrying Different Mutations: A Pilot Study.}, journal = {Cells}, volume = {14}, number = {13}, pages = {}, pmid = {40643479}, issn = {2073-4409}, support = {N. 68155.//The study was supported by the AGING Project for Department of Excellence at the Department of Translational Medicine (DIMET), Università del Piemonte Orientale, Novara, Italy and DIG-ALS, AriSLA Foundation. AF was supported by CSP - Compagnia San Paolo T/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/pathology ; *Induced Pluripotent Stem Cells/metabolism/pathology ; Pilot Projects ; Kruppel-Like Factor 4 ; *Mutation/genetics ; *Transcriptome/genetics ; *Neural Stem Cells/metabolism/pathology ; Female ; Middle Aged ; Male ; Cell Differentiation ; C9orf72 Protein/genetics ; Aged ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease affecting motor neurons with a phenotypic and genetic heterogeneity and elusive molecular mechanisms. With the present pilot study, we investigated different genetic mutations (C9orf72, TARDBP, and KIF5A) associated with ALS by generating induced pluripotent stem cells (iPSCs) from peripheral blood of ALS patients and healthy donors. iPSCs showed the typical morphology, expressed stem cell markers both at RNA (OCT4, SOX2, KLF4, and c-Myc) and protein (Oct4, Sox2, SSEA3, and Tra1-60) levels. Moreover, embryoid bodies expressing the three germ-layer markers and neurospheres expressing neural progenitor markers were generated. Importantly, the transcriptomic profiles of iPSCs and neurospheres were analyzed to highlight the differences between ALS patients and healthy controls. Interestingly, the differentially expressed genes (DEGs) shared across all ALS iPSCs are linked to extracellular matrix, highlighting its importance in ALS progression. In contrast, ALS neurospheres displayed widespread deficits in neuronal pathways, although these DEGs were varied among patients, reflecting the disease's heterogeneity. Overall, we generated iPSC lines from ALS patients with diverse genetic backgrounds offering a tool for unravelling the intricate molecular landscape of ALS, paving the way for identifying key pathways implicated in pathogenesis and the disease's phenotypic variability.}, } @article {pmid40643147, year = {2025}, author = {Vélez-Gómez, B and Cabrera-Serrano, M and Paradas, C}, title = {Utilization of patient-reported outcome measures in amyotrophic lateral sclerosis management: a cross-sectional study of Spanish neurologists.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {}, number = {}, pages = {1-9}, doi = {10.1080/21678421.2025.2523940}, pmid = {40643147}, issn = {2167-9223}, abstract = {Objective: Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disease that significantly impacts quality of life. Patient-Reported Outcome Measures (PROMs) offer a patient-centered approach by capturing self-reported assessments of symptoms and well-being. Despite their recognized value, PROM integration into ALS management remains inconsistent. This study evaluates the attitudes, practices, and barriers experienced by Spanish neurologists regarding PROM use in ALS care. Methods: A cross-sectional survey was distributed to Spanish neurologists specializing in neuromuscular disorders. The questionnaire assessed familiarity with and use of PROMs, as well as perceived benefits and barriers to their implementation. Statistical analysis included descriptive statistics, group comparisons, and exploratory factor analysis (EFA) to identify underlying factors influencing PROM use. Results: Among 60 neurologists surveyed, 93.3% were familiar with PROMs, yet only 18.3% used them routinely. PROM use did not vary significantly with years of experience, type of clinical setting, exclusive dedication to neuromuscular disorders, or the percentage of time spent on patient care. The only variable approaching significance was the number of ALS patients managed daily, with higher patient volumes associated with more frequent PROM use. Over 70% of non-users cited limited consultation time as a barrier; however, factor analysis indicated that time constraints were not a substantial limitation. PROMs were valued for supporting clinical decision-making, monitoring disease progression, and improving patient engagement. Conclusions: While PROMs are widely recognized for their potential in ALS care, barriers hinder their use. Targeted training, simplified tools, and culturally adapted PROMs are needed to facilitate broader adoption and improve outcomes.}, } @article {pmid40642867, year = {2025}, author = {Pang, C and Cao, W and Xie, J and Li, Y and Zhu, L and Yu, H and Fan, D and Deng, B}, title = {Prediagnosis Insights Into Amyotrophic Lateral Sclerosis: Clinical Symptoms and Medication Use.}, journal = {Journal of cachexia, sarcopenia and muscle}, volume = {16}, number = {4}, pages = {e70003}, pmid = {40642867}, issn = {2190-6009}, support = {81901273//National Natural Science Foundation of China/ ; ZCLY24H0903//Natural Science Foundation of Zhejiang Province/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/drug therapy/epidemiology/mortality ; Female ; Male ; Aged ; Middle Aged ; Incidence ; United Kingdom/epidemiology ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) has a prolonged latency period, though its preclinical characteristics remain poorly understood. This study uses UK Biobank data to explore and compare ALS's pre-diagnostic features, including symptoms and medication use, aiming to provide insights into the disease's underlying mechanisms.

METHODS: Clinical symptoms and medications were identified from self-reports, hospital records, and death registry data. Propensity score matching was used to match ALS with Alzheimer's disease (AD) and Parkinson's disease (PD), ensuring balance in socioeconomic factors to compare symptoms 0-5 years before diagnosis. Cox regression analysis was applied to assess the associations between medication use and the risk of incident ALS and mortality after ALS diagnosis.

RESULTS: A total of 753 ALS cases were observed in 502 417 participants, with an incidence rate of 10.58 per 100 000 person-years. In the ALS cohort, the male-to-female ratio was 2.9, with a median age at onset of 64.61 years (Interquartile range (IQR): 56.80-71.31) and a median survival time post-diagnosis of 9.08 months (IQR: 3.18-18.98), while females (log-rank p = 0.038) and individuals with earlier (< 64.61 years) disease onset (log-rank p < 0.001) had longer survival periods. In the 5 years prior to diagnosis, ALS showed a higher incidence of falls compared to ad (11.3% vs. 3.2%, p < 0.001), but a lower incidence than PD (10.7% vs. 28.3%, p < 0.001). Additionally, ALS had a lower incidence of depression (4.6% vs. 25.6%, p < 0.001), anxiety (3.5% vs. 18.1%, p < 0.001), sleep disorders (1.4% vs. 7.2%, p < 0.001), hypotension (3.4% vs. 30.5%, p < 0.001), constipation (0.3% vs. 4.9%, p < 0.001), and urinary dysfunction (2.2% vs. 8.7%, p < 0.001) compared with PD. The use of calcium channel blockers may be a risk factor for incident ALS (adjusted HR 1.61, 95% CI: 1.22-2.12, p < 0.001).

CONCLUSIONS: Pre-diagnostic presentations of falls are more frequent in ALS than in AD, but less frequent than in PD. However, ALS exhibits fewer psychiatric symptoms and autonomic dysfunction compared with PD. The use of calcium channel blockers may be associated with an increased risk of developing ALS in the future.}, } @article {pmid40642215, year = {2025}, author = {Ahmed, Z and Samaddar, S and Hassieb, M and Sadek, R and Morozova, V and Begum, S}, title = {Multi-path direct current spinal stimulation extended survival in the SOD1-G93A model of amyotrophic lateral sclerosis.}, journal = {Frontiers in neurology}, volume = {16}, number = {}, pages = {1594169}, pmid = {40642215}, issn = {1664-2295}, abstract = {INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that affects motor neurons in the spinal cord and brain. We have developed a novel non-invasive approach, MultiPath-DCS, which utilizes direct current stimulation at multiple sites along the neural axis to provide simultaneous spinal and peripheral stimulation targeted at the affected limbs. MultiPath-DCS modulates the excitability of spinal cord neurons. This effect is significant for ALS, as motor neuron hyperexcitability is a fundamental characteristic of the disease.

METHODS: This study used a transgenic mouse model of ALS (SOD1-G93A). Anodal-MultiPath-DCS was applied with six electrodes: three on the spine (centered on T13 and with an anodal polarity), two on the sciatic nerves (one on each nerve), and one on the abdomen. Mice were divided into two groups (stimulated vs. unstimulated or sham-stimulated). The stimulated animals received stimulation for one hour a day, three times a week, for three weeks. Survival was calculated from the onset of the disease and birth until the animal's endpoint. We also performed various electrophysiological and molecular experiments to uncover the mechanism of action.

RESULTS: We demonstrated molecular changes induced by anodal MultiPath-DCS, including (a) reduced expression of mutant SOD1 protein, (b) decreased expression of elevated NKCC1, (c) reduced phosphorylated tau, (d) increased expression of HSP70, and (e) increased expression of LC3B. Additionally, we found that treatment with Anodal-MultiPath-DCS (anode on the spinal column) reduces long-term neuronal spinal excitability, slows the progression of muscle weakness, and extends the lifespan of stimulated mice. The mean survival time in the control group was 12.4 days. In comparison, the mean survival time in the stimulated group was 21.6 days using a therapeutic stimulation paradigm, representing a 74% increase in survival from disease onset. Spinal motor neuron survival showed a 54% increase in stimulated compared to non-stimulated groups.

DISCUSSION: Combined, this data provides evidence that Anodal-MultiPath-DCS reduces hyperexcitability and enhances the clearance of misfolded proteins by modulating autophagy and proteolytic systems. By decreasing spinal excitability and clearing toxic proteins from motor neurons, Anodal-MultiPath-DCS promotes survival and could serve as a disease-modifying intervention for ALS.}, } @article {pmid40641248, year = {2025}, author = {Yang, K and Liu, Y and Deng, W and Gong, Z and Huang, L and Li, Z and Zhang, M}, title = {Astrocytes Contribute to Motor Neuron Degeneration in ALS via the TRAIL-DR5 Signaling Pathway.}, journal = {Journal of neurochemistry}, volume = {169}, number = {7}, pages = {e70146}, pmid = {40641248}, issn = {1471-4159}, support = {2024AOXIANG05//Research and Innovation Team Project for Scientific Breakthroughs at Shanxi Bethune Hospital/ ; 82271478//National Natural Science Foundation of China/ ; }, mesh = {Animals ; *Amyotrophic Lateral Sclerosis/pathology/metabolism/genetics ; *Motor Neurons/pathology/metabolism ; Mice ; *TNF-Related Apoptosis-Inducing Ligand/metabolism ; *Receptors, TNF-Related Apoptosis-Inducing Ligand/metabolism ; *Signal Transduction/physiology ; *Astrocytes/metabolism/pathology ; *Nerve Degeneration/pathology/metabolism ; Mice, Transgenic ; Humans ; Superoxide Dismutase-1 ; Disease Models, Animal ; Superoxide Dismutase/genetics ; Mice, Inbred C57BL ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by the degeneration of both upper and lower motor neurons. The mechanisms underlying the selective degeneration of motor neurons in ALS remain poorly understood, underscoring the need for further investigation into the factors driving this process. In this study, we utilized ALS mouse models and an in vitro NSC34 motor neuron cell line expressing the SOD1[G93A] mutation to identify a novel pathogenic mechanism wherein astrocyte-secreted Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) binds to Death Receptor 5 (DR5)on motor neurons, leading to caspase-8 activation and subsequent neuronal death. Blocking DR5 with neutralizing antibodies significantly attenuated TRAIL-induced motor neuron death. These findings provide the first evidence that TRAIL may serve as a potential therapeutic target in ALS, offering new insights into the mechanisms of motor neuron degeneration in this disease.}, } @article {pmid40641139, year = {2025}, author = {Sun, Y and Wei, K and Liao, X and Wang, J and Gao, L and Pang, B}, title = {Lipid metabolism in microglia: Emerging mechanisms and therapeutic opportunities for neurodegenerative diseases (Review).}, journal = {International journal of molecular medicine}, volume = {56}, number = {3}, pages = {}, pmid = {40641139}, issn = {1791-244X}, mesh = {*Microglia/metabolism/pathology ; Humans ; *Lipid Metabolism ; Animals ; *Neurodegenerative Diseases/metabolism/pathology/therapy ; }, abstract = {Neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis, are characterized by progressive neuronal loss and neuroinflammation, with microglial dysfunction emerging as a central driver of pathogenesis. Microglia, the central nervous system‑resident immune cells, exhibit dual pro‑inflammatory and anti‑inflammatory phenotypes, dynamically regulated by lipid metabolic reprogramming. Chronic activation of M1 microglia exacerbates neuronal damage, while M2 microglia promote tissue repair via phagocytic clearance and neurotrophic factor secretion. Lipid dysregulation‑marked by ceramide accumulation, cholesterol esterification defects and oxidized lipid‑driven neuroinflammation‑critically modulates microglial polarization. Mechanistic studies reveal that mitochondrial dysfunction, lysosomal stress and ferroptosis intersect with lipid metabolic pathways to amplify neurotoxicity. Therapeutic strategies targeting lipid homeostasis, such as TREM2 agonism, demonstrate efficacy in preclinical models by restoring microglial function and mitigating pathology. This review synthesizes emerging evidence linking microglial lipid metabolism to NDD progression, highlighting novel biomarkers and therapeutic avenues to disrupt the lipid‑neuroinflammation axis in neurodegeneration.}, } @article {pmid40640965, year = {2025}, author = {Wright, K and Warren, F and Bucci, S and Dunn, BD and Jones, S and O'Mahen, H and Taylor, RS and Medina-Lara, A}, title = {A study protocol for a randomized controlled feasibility trial of behavioural therapy for interepisode bipolar symptoms (STABILISE).}, journal = {Pilot and feasibility studies}, volume = {11}, number = {1}, pages = {97}, pmid = {40640965}, issn = {2055-5784}, support = {NIHR302220//National Institute for Health and Care Research/ ; }, abstract = {BACKGROUND: In between episodes of (hypo) mania and major depression, people with bipolar disorder can experience ongoing low mood or mood instability, and these may also be present as part of cyclothymic disorder. This is a phase II evaluation of an adapted form of behavioural therapy (STABILISE) for inter-episode bipolar symptoms. The study aims to establish the feasibility and acceptability of the therapy and research procedures, including an economic component, to inform a future definitive trial.

METHODS: Patients will be randomised 1:1 to either Treatment as Usual (control arm) or Treatment as Usual plus STABILISE intervention (intervention arm). Follow up points will be at 14, 30 and 52 weeks post eligibility confirmation, with 30 weeks as the primary end point. We aim to recruit 60 individuals meeting diagnostic criteria for a Bipolar Spectrum Disorder, and reporting ongoing bipolar symptoms (low mood or mood instability) outside of a manic or severe depressive episode. Feasibility and acceptability will be examined through recruitment and retention rates, completion rates for the candidate primary outcome measures (PHQ9, ALS-SF, QoL.BD and BRQ) and feedback from participants on their experience of study participation and therapy. Proceeding to a definitive trial will be indicated if the following criteria are met: (i) trial participation is deemed, or can be made, sufficiently safe; (ii) recruitment rate indicates that larger-scale recruitment would be feasible (recruitment rate of at least two participants per month within at least one site, with mitigation plan if overall target sample size not met); (iii) for candidate primary outcome measure follow up data is available at 30 weeks from at least 75% of participants, or from between 55 and 74% with clear plan for improvement.

DISCUSSION: This study is a randomised, controlled feasibility trial that builds on an initial case series of the STABILISE approach. The findings will be used to establish whether a future, definitive trial is feasible and to refine the research procedures and therapy protocol.

TRIAL REGISTRATION: ISRCTN18207465. Registered 13th March 2024, https://www.isrctn.com/ISRCTN18207465 .}, } @article {pmid40640916, year = {2025}, author = {Lemarchant, S and Engelhardt, B and Cicchetti, F and Bix, GJ and Janus, A and Godfrin, Y and Blasco, H and Campbell, M and de Rus Jacquet, A}, title = {Restoring brain barriers: an innovative approach for treating neurological disorders.}, journal = {Fluids and barriers of the CNS}, volume = {22}, number = {1}, pages = {72}, pmid = {40640916}, issn = {2045-8118}, mesh = {Humans ; *Blood-Brain Barrier/drug effects/physiopathology/pathology/metabolism ; *Nervous System Diseases/drug therapy/therapy/pathology ; Animals ; }, abstract = {The complex etiology of neurological disorders is a major challenge to the identification of therapeutic candidates. Tackling brain vascular dysfunction is gaining attention from the scientific community, neurologists and pharmaceutical companies, as a novel disease-modifying strategy. Here, we provide evidence that at least 41% of neurological diseases and related conditions/injuries display a co-pathology of blood-brain and blood-spinal cord barrier alterations and dysfunctions, and we discuss why this figure may represent only a fraction of a larger phenomenon. We further provide clinical evidence that barrier status may contribute to pathological and functional outcomes in patients. Finally, we discuss drug candidates under development to repair brain barriers.}, } @article {pmid40640892, year = {2025}, author = {Noh, MY and Kwon, HS and Kwon, MS and Nahm, M and Jin, HK and Bae, JS and Kim, SH}, title = {Biomarkers and therapeutic strategies targeting microglia in neurodegenerative diseases: current status and future directions.}, journal = {Molecular neurodegeneration}, volume = {20}, number = {1}, pages = {82}, pmid = {40640892}, issn = {1750-1326}, support = {RS-2024-00348451//Korea Dementia Research Center/ ; }, mesh = {Humans ; *Microglia/metabolism ; *Neurodegenerative Diseases/metabolism/therapy ; *Biomarkers/metabolism ; Animals ; }, abstract = {Recent advances in our understanding of non-cell-autonomous mechanisms in neurodegenerative diseases (NDDs) have highlighted microglial dysfunction as a core driver of disease progression. Conditions such as Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), and frontotemporal dementia (FTD) share features of impaired microglial phagocytosis, chronic neuroinflammation, and metabolic dysregulation. These insights have prompted new therapeutic strategies targeting microglial function and emphasized the need for reliable biomarkers to monitor disease progression and treatment response. Well-established therapeutic targets, such as triggering receptor expressed on myeloid cells 2 (TREM2), progranulin (PGRN), and sortilin (SORT1), along with emerging candidates including LILRB4, P2Y6R, TAM receptors, and neuroinflammation-related markers, are discussed alongside novel blood, cerebrospinal fluid (CSF), and imaging biomarkers. Despite notable progress, many of these biomarkers remain restricted to preclinical studies and face translational challenges due to species-specific differences, lack of standardization, and clinical heterogeneity. Emerging technologies-including single-cell omics, spatial transcriptomics, and artificial intelligence (AI)-driven integration of multimodal data-offer new opportunities to align biomarker profiles with evolving disease states and improve patient stratification. Building on the model of companion diagnostics (CDx) in oncology, integrating multimodal biomarker strategies holds promise for guiding personalized interventions, improving clinical outcomes, and deepening our mechanistic understanding of microglial contributions across the neurodegenerative spectrum.}, } @article {pmid40640855, year = {2025}, author = {Soliman, SS and Talib, NFA and Elghobashy, MR and Rahman, MAA}, title = {Sustainable analysis of COVID-19 Co-packaged paxlovid: exploring advanced sampling techniques and multivariate processing tools.}, journal = {BMC chemistry}, volume = {19}, number = {1}, pages = {206}, pmid = {40640855}, issn = {2661-801X}, abstract = {The drawbacks of random sampling not only hinder the development of more reliable and efficient methods but also weaken their accuracy, predictive abilities, and validity across several domains. During the current study, a pioneering statistical technique namely, Latin Hypercube Sampling (LHS) was integrated with different multivariate chemometric models namely; Partial Least Squares (PLS), Genetic Algorithm‑Partial Least Squares (GA-PLS), Artificial Neural Networks (ANN), and Multivariate Curve Resolution‑Alternating Least Squares (MCR-ALS). This integration aimed to achieve full data coverage and thereby enhance the predictive powers of these models. Being of clinical significance, Paxlovid[®], a newly co-packaged antiCOVID-19 drug containing ritonavir (RNV)-boosted nirmatrelvir (NMV), was utilized as a study subject to demonstrate the powerful potentials of LHS in enhancing models' robustness and predictive accuracy. The LHS technique was able to provide well-interpreted and informative samples by capturing essential variabilities across the input space without any increase in sample numbers. It was compared and outperformed the random sampling Monte Carlo technique. A comprehensive comparison between the developed models was held where the RMSEP was relatively reduced by 14.1%, 8.9%, 53.1%, and 34.6% for RNV and NMV, respectively using the ANN and MCR-ALS models. Various preprocessing techniques were employed to improve signal quality for PLS construction, yielding superior results (RMSEC of 0.19 for both RNV and NMV) compared to the original, unprocessed spectral data (RMSEC of 0.21 for both RNV and NMV). The Principal Component Analysis score plot was constructed, confirming the consistency of the dataset and the absence of systematic errors, enhancing confidence in the models' robustness. A new hybrid variable selection strategy (GA-ICOMP-PLS) was developed to enhance the robustness and parsimony of the GA-PLS model. Prediction error values of 0.15 and 0.14 were successfully achieved for RNV and NMV, respectively, indicating strong predictive power and generalization. Consistent with sustainability and eco-friendly goals, the current study pioneers the usage of green-blue-white alternatives to conventional analytical methods. A comprehensive assessment was conducted using the "Sample Preparation Metric of Sustainability", the "Analytical Greenness metric for Sample Preparation" and the "Analytical Greenness metric" alongside two solvent sustainability evaluation tools. These evaluations yielded promising results, with green quadrant classification and high scores of 5.89, 0.67, and 0.82 for each metric, respectively, as well as satisfactory t- and F-test values. Moreover, the models achieved outstanding results on the RGB12 metric and Blueness Applicability Grade Index, scoring 96.8% and 82.5, respectively, highlighting their broad applicability, high efficiency, and alignment with eco-friendly analytical practices.}, } @article {pmid40640528, year = {2025}, author = {McGuigan, A and Blair, HA}, title = {Tofersen: A Review in Amyotrophic Lateral Sclerosis Associated with SOD1 Mutations.}, journal = {CNS drugs}, volume = {39}, number = {9}, pages = {903-912}, pmid = {40640528}, issn = {1179-1934}, abstract = {Tofersen (QALSODY[®]) is the first drug approved for the treatment of amyotrophic lateral sclerosis (ALS) associated with superoxide dismutase 1 (SOD1) mutations. Tofersen is an antisense oligonucleotide that induces SOD1 mRNA degradation. In the 28-week, placebo-controlled, multinational, phase III VALOR trial, intrathecally administered tofersen reduced plasma concentrations of neurofilament proteins (biomarker for neuro-axonal injury) and total SOD1 protein in cerebrospinal fluid in patients with SOD1 mutation-associated ALS. These reductions were sustained in a long-term, open-label extension study. The decline in functional outcomes was not significantly reduced with tofersen treatment compared with placebo in the 28-week phase III trial, although in the longer-term open-label study, early tofersen initiation was associated with slowed functional decline versus delayed tofersen initiation. Tofersen had an acceptable tolerability profile in clinical trials with a favourable benefit-to-risk balance. In summary, tofersen is a new disease-modifying therapy for patients with ALS attributed to an SOD1 mutation, offering reductions in levels of a biomarker associated with neurodegeneration and disease progression, with an acceptable tolerability profile.}, } @article {pmid40640025, year = {2025}, author = {Kim, S and Yang, M and Ku, B and Cha, E and Seo, W and Son, I and Kang, H and Kim, D and Song, B and Yang, CS and Kim, S}, title = {Corrigendum to "Efficacy of mecasin for treatment of amyotrophic lateral sclerosis: A phase IIa multicenter randomized double-blinded placebo-controlled trial" [J. Ethnopharmacol. 320 (2023) 116670].}, journal = {Journal of ethnopharmacology}, volume = {}, number = {}, pages = {120239}, doi = {10.1016/j.jep.2025.120239}, pmid = {40640025}, issn = {1872-7573}, } @article {pmid40637865, year = {2025}, author = {Coleman, A and Touzé, A and Farag, M and Pengo, M and Murphy, MJ and Hassan, Y and Thackeray, O and Fayer, K and Field, S and Nakajima, M and Broom, EL and Hobbs, NZ and Huxford, B and Donkor, N and Camboe, E and Dey, KC and Zirra, A and Ahmed, A and Gameiro Costa, AR and Sorrell, H and Zampedri, L and Lombardi, V and Wade, C and Mangion, S and Fneich, B and Heslegrave, A and Zetterberg, H and Scahill, R and Noyce, A and Malaspina, A and Chataway, J and Tabrizi, SJ and Byrne, LM}, title = {Evaluating finger-prick blood collection for remote quantification of neurofilament light in neurological diseases.}, journal = {Journal of neurology}, volume = {272}, number = {8}, pages = {501}, pmid = {40637865}, issn = {1432-1459}, support = {MR/W026686/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Humans ; *Neurofilament Proteins/blood ; Male ; Female ; Middle Aged ; Biomarkers/blood ; Adult ; Aged ; *Blood Specimen Collection/methods/standards ; *Nervous System Diseases/blood/diagnosis ; Cohort Studies ; Parkinson Disease/blood ; Amyotrophic Lateral Sclerosis/blood ; Huntington Disease/blood/diagnosis ; Multiple Sclerosis/blood ; }, abstract = {Promising blood-based biomarkers of neuropathology have emerged with potential for therapeutic development and disease monitoring. However, these tools will require specialist tertiary services for integration into clinical management. Remote sampling for biomarker assessment could reduce burden of in-person clinical visits for such tests as well as increasing the sampling frequency and patient geographical outreach. Here, we evaluated a finger-prick blood collection approach for remote quantification of neurofilament light (NfL), a candidate blood-based biomarker evident in various neurological disorders, and other exploratory markers of neuronal injury and neuroinflammation (GFAP, tau). Matched samples from venepuncture and finger-prick were collected and processed into plasma and/or serum to directly compare analyte levels from a multi-disease discovery cohort (n = 54 healthy controls; n = 57 Huntington's disease (HD); n = 34 multiple sclerosis; n = 7 amyotrophic lateral sclerosis; n = 11 Parkinson's disease), and a HD confirmatory cohort (n = 57 healthy controls; n = 64 HD). Two delayed processing conditions were compared, three- and seven-day delay, simulating ambient shipment. Capillary NfL and GFAP concentrations were equivalent to those in venous serum and plasma in the multi-disease discovery cohort and HD confirmatory cohort. Only NfL remained stable after a seven-day processing delay in both venous and capillary serum samples. Using NfL concentrations from capillary blood, we replicated previously published disease group differences measured in venous blood. This data supports our finger-prick approach for remote collection and quantification of NfL. With the widespread applications for NfL across the spectrum of neurological disorders, this has the potential to transform disease monitoring, prognosis, and therapeutic development within clinical practice and research.}, } @article {pmid40635530, year = {2025}, author = {Manicardi, A and Mora, G and Araujo, ALS and Gaines, TA and Lozano-Juste, J and Torra, J}, title = {Analysis of multiple-herbicide resistant Amaranthus palmeri populations from Spain points to an introduction of the eccDNA from America.}, journal = {Pest management science}, volume = {}, number = {}, pages = {}, doi = {10.1002/ps.70034}, pmid = {40635530}, issn = {1526-4998}, support = {PRTR-C17.I1//European Union NextGenerationEU, AGROALNEXT, GVA/ ; 801586//H2020 Marie Skłodowska-Curie Actions/ ; PID2020-113229RB-C42//Spanish State Research Agency and the European Regional Development Fund, EU (ERDF)/ ; PID2021-128826OAI00//Spanish MCIN/AEI/ ; RYC2020-029097-I//Spanish MCIN/AEI/ ; RYC2018-023866-I//Spanish MCIN/AEI/ ; CISEJI/2022/26//Generalitat Valenciana, Plan GenT/ ; RED2022-134285-T(PalmerNET)//Spanish Ministry of Science and Innovation/ ; }, abstract = {BACKGROUND: The herbicide-resistant invasive weed species Amaranthus palmeri threatens agricultural production and native plant ecology in Spain, as well as in other European countries. Understanding whether herbicide resistance alleles evolve in situ or are introduced via gene flow remains unclear. To address this, we characterized multiple resistance to acetolactate synthase (ALS)-- and 5-enolpyruvylshikimate-3phosphate synthase (EPSPS)-inhibiting herbicides in two Spanish A. palmeri populations at the plant level. Additionally, we analyzed the extra-chromosomal circular DNA (eccDNA) to determine whether glyphosate resistance resulted from local selection pressure or was introduced by gene flow.

RESULTS: Both populations exhibit individuals that survived both herbicide MoA, with multiple resistance mechanisms to ALS- and EPSPS-inhibiting herbicides. Eight different ALS allele mutations were identified in resistant plants, including Pro-197-Ile, reported only in one species previously. Glyphosate resistance in the two populations is to the result of gene duplication mediated by eccDNA. Spanish and North American eccDNAs showed complete identity, with no single nucleotide polymorphisms (SNPs) found between the partial analyzed sequences of noncoding regions.

CONCLUSION: We confirm for the first time in Europe resistance to ALS and EPSPS inhibitors at both the population and individual levels in two Spanish A. palmeri populations. The absence of SNPs in the eccDNA from Spanish populations compared to the reference American sequence and the presence of target-site mutations in the ALS gene occurred without selective pressure from ALS herbicides, suggests that the origin of resistance traits may have evolved elsewhere and been introduced from the place of origin to Spain. However, it is important to note that the limited number of populations studied and the partial sequencing of eccDNA do not provide definitive confirmation of the exact origins of resistance mechanisms. This work raises concerns about the arrival of this and potentially other new herbicide-resistant A. palmeri populations in Europe posing challenges for management. © 2025 The Author(s). Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.}, } @article {pmid40633900, year = {2025}, author = {Singh, N and Mishra, D and Gomes, J}, title = {Deleterious Sequestosome 1 mutations G262R and P438L in amyotrophic lateral sclerosis cause autophagy and oxidative stress imbalance.}, journal = {Neuroscience}, volume = {581}, number = {}, pages = {233-246}, doi = {10.1016/j.neuroscience.2025.07.011}, pmid = {40633900}, issn = {1873-7544}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology ; *Sequestosome-1 Protein/genetics/metabolism ; *Autophagy/genetics ; *Oxidative Stress/genetics ; Cell Line, Tumor ; DNA-Binding Proteins/metabolism ; Signal Transduction ; Mutation ; NF-E2-Related Factor 2/metabolism ; }, abstract = {Amyotrophic Lateral Sclerosis (ALS) is a severe neurodegenerative disease (NDD) prevalent across the world. It is known that mutations in ALS associated genes can cause imbalances between cellular processes such as apoptosis, necroptosis, autophagy and proteasomal degradation that remove dysfunctional and aggregating proteins. Two rare missense variants namely G262R (G > A) and P438L (C > T) in Sequestosome 1 (SQSTM1), were identified by our group in a cohort of Indian ALS patients. SQSTM1 codes for p62, which is an autophagy adaptor protein involved in several signaling pathways. In this study, we investigated how these SQSTM1 mutations affect autophagy and the oxidative stress response pathway in SH-SY5Y cells through quantitative RT-PCR, immunoblotting and confocal microscopy. In addition, we examined how changes in the downstream signaling pathways alters nuclear-cytoplasmic localization of TDP-43 protein, a marker protein usually found in cytoplasmic inclusions in ALS patient tissues. We observed up-regulation of autophagy marker proteins LC3-II and ubiquitin, and down-regulation of oxidative stress marker protein Nrf2. Along with LC3-II, p-OPTN and ATG5, proteins that are also associated with autophagy were up-regulated. We also observed an increase in cytoplasmic localization of TDP-43 protein in cells expressing these p62 mutant proteins. Overall, our study provides evidence that the G262R (G > A) and P438L (C > T) mutations are deleterious through mechanisms that increase cytoplasmic localization of TDP-43, and adversely affect the autophagy and oxidative stress response pathway.}, } @article {pmid40633079, year = {2025}, author = {Al-Akeedi, JM and Khudiar, HH and Al Muhtaser, STM and Al-Fahham, AA}, title = {Genotypes of Candida albicans and its cooperative interaction with Streptococci isolated from throat infections.}, journal = {Polski merkuriusz lekarski : organ Polskiego Towarzystwa Lekarskiego}, volume = {53}, number = {3}, pages = {378-383}, doi = {10.36740/Merkur202503112}, pmid = {40633079}, issn = {1426-9686}, mesh = {*Candida albicans/genetics/isolation & purification/physiology ; Humans ; Genotype ; Biofilms/growth & development ; *Streptococcus/isolation & purification/genetics/physiology ; *Streptococcal Infections/microbiology ; *Pharyngitis/microbiology ; }, abstract = {OBJECTIVE: Aim: This study was aimed to detect and determine genotypes of Candida albicans and its cooperative interaction with streptococci isolated from throat infections.

PATIENTS AND METHODS: Materials and Methods: This survey was carried out during November 2023 and March 2024 to collect a total of 80 throat swab samples from patients in in Al-Sadr Medical City in Najaf during. Candida was isolated from culturing throat swab samples on Sabouraud agar, and Blood agar. Each isolate (Candida & Streptococci) enhanced in monoculture using enrichment media; Potato Dextrose broth. Molecular assay included detecting three of biofilm forming genes; Als1, Als2, Als3.

RESULTS: Results: Twelve out of fifteen Candida isolates showed increase in number after mixing with Streptococci and incubation. In contrast, three isolates showed no change or decrease after mixing in co-culture media. Five Candida isolates (out of 15 isolates) were positive in gel electrophoresis to three biofilm genes classified as first genotype (CALSG1). Four Candida isolates were negative in gel electrophoresis to three biofilm genes, classified as second genotype (CALSG2). Other Candida isolates were positive to one or two of three biofilm genes, classified with genotypes (CALSG3, CALSG4, CALSG5 and CALSG6).

CONCLUSION: Conclusions: Candida albicans has biofilm formation genes (Als), which attract other organisms, like streptococci resulting in synergistic interaction. Despite the presence of some Als genes, it's not necessary to found strong biofilm results as Als genes may not be translated to form biofilm.}, } @article {pmid40632651, year = {2025}, author = {Dos Santos, M and Bezprozvannaya, S and McAnally, JR and Cai, C and Liu, N and Olson, EN}, title = {A mechanistic basis of fast myofiber vulnerability to neuromuscular diseases.}, journal = {Cell reports}, volume = {44}, number = {7}, pages = {115959}, doi = {10.1016/j.celrep.2025.115959}, pmid = {40632651}, issn = {2211-1247}, mesh = {Animals ; Humans ; Mice ; *Muscle Fibers, Fast-Twitch/metabolism/pathology ; *Neuromuscular Diseases/pathology/metabolism/genetics ; Amyotrophic Lateral Sclerosis/pathology/metabolism/genetics ; Muscular Atrophy/pathology/genetics/metabolism ; Muscle, Skeletal/metabolism/pathology ; Male ; Mice, Inbred C57BL ; Muscle Fibers, Skeletal/metabolism ; }, abstract = {Neuromuscular diseases such as amyotrophic lateral sclerosis and sarcopenia cause muscle atrophy, which preferentially affects fast-twitch glycolytic myofibers. The mechanisms underlying the susceptibility of fast myofibers to disease remain unclear. To investigate this, we analyzed the transcriptional profiles of myonuclei from denervated muscle fibers. We found that the fast muscle gene program and the transcription factor Maf were repressed upon denervation. Overexpression of Maf in mice prevented loss of muscle mass caused by denervation by repressing atrophic genes and restoring fast gene expression. Similar repression of fast genes and Maf was observed in muscles from mice and humans with amyotrophic lateral sclerosis. Notably, Maf overexpression in human skeletal muscle cells in vitro prevented muscle atrophy and activated the expression of fast muscle genes. Our findings highlight a key role for Maf in maintaining muscle mass and could offer a promising therapeutic strategy to preserve muscle function during disease, aging, and injury.}, } @article {pmid40632556, year = {2025}, author = {Shaked, R and Katz, M and Cohen-Dvashi, H and Diskin, R}, title = {The prefusion structure of the HERV-K (HML-2) Env spike complex.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {122}, number = {28}, pages = {e2505505122}, pmid = {40632556}, issn = {1091-6490}, support = {209/20//Israel Science Foundation (ISF)/ ; }, mesh = {*Endogenous Retroviruses/chemistry/metabolism/genetics ; Cryoelectron Microscopy ; Humans ; Models, Molecular ; *Gene Products, env/chemistry/metabolism ; }, abstract = {The human endogenous retrovirus K (HERV-K) is a retrovirus that got assimilated into the human genome in ancient times and has been inherited in our germline ever since. It enters cells using a class-I spike protein (Env) that mediates receptor recognition and membrane fusion. On top of having a biological role during development, HERV-K is activated in amyotrophic lateral sclerosis, various cancers, and other pathological conditions. Antibodies that target the HERV-K spike complex have therapeutic value, flagging the spike as a novel drug target. Here, we use cryo-EM to determine the trimeric structure of the HERV-K spike. The spike presents a distinct structure, which substantially differs from other class-I fusogens. Nevertheless, some general architectural features suggest a common origin with other retroviruses. The ability to structurally characterize the HERV-K spike may facilitate the development of antibody-based therapies.}, } @article {pmid40631777, year = {2025}, author = {LaBarge, B and Lorenz, FJ and Gniady, JP}, title = {Association of Laryngeal Dystonia With Common Neurologic Disorders.}, journal = {The Laryngoscope}, volume = {}, number = {}, pages = {}, pmid = {40631777}, issn = {1531-4995}, support = {UL1 TR002014/TR/NCATS NIH HHS/United States ; }, abstract = {OBJECTIVE: Laryngeal dystonia is a heterogenous disorder consisting of involuntary spasms of laryngeal muscles. There are multiple forms including adductor, abductor, and mixed phenotypes. The disorder is thought to be multifactorial, with various reported associations with family history of dystonia or movement disorders. The relationship between laryngeal dystonia and various neurologic disorders is not well defined in the literature.

METHODS: We utilized the TriNetX de-identified electronic medical record database system spanning 2010-2023 to assess the prevalence of laryngeal dystonia with common neurologic disorders, compared to an age-sex matched control population. We included patients with the laryngeal spasm J38.5 ICD-10 code and 64617 CPT code, in order to categorize laryngeal dystonia patients undergoing chemodenervation.

RESULTS: The patient cohort consisted of approximately 4000 patients. 75% were female, 71% were white, and the mean age was 61 years. The laryngeal dystonia population had an elevated relative risk of Parkinson's disease (RR = 2.7, 1.8-3.9, 95% CI). In contrast, the relative risk of Alzheimer's disease was decreased in the laryngeal dystonia population (RR = 0.28, 0.16-0.48, 95% CI). There were no differences between the laryngeal dystonia and control populations for multiple sclerosis, amyotrophic lateral sclerosis, epilepsy, migraine, muscular dystrophy, or cerebral palsy.

CONCLUSION: Laryngeal dystonia patients have a significantly greater association with Parkinson's disease and less association with Alzheimer's disease compared to the control population. There were no meaningful associations with the remainder of the neurologic conditions included in the study.}, } @article {pmid40631187, year = {2025}, author = {Scheutzow, AN and Thanthirige, S and Siffer, G and Sorkin, AD and Wohlever, ML}, title = {E3 ligase recruitment by UBQLN2 protects substrates from proteasomal degradation.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2024.07.04.602059}, pmid = {40631187}, issn = {2692-8205}, abstract = {Ubiquilins are a family of proteins critical to cellular proteostasis that are also linked to several neurodegenerative diseases, with specific mutations in UBQLN2 causing dominant, X-linked ALS. Despite an initial characterization as proteasomal shuttle factors, Ubiquilins have paradoxically been reported to stabilize numerous substrates. The basis of this triage decision remains enigmatic. Many other fundamental aspects of Ubiquilin function are unclear at the mechanistic level, such as the physiological significance of Ubiquilin phase separation, the unique role of each Ubiquilin paralog, and the mechanistic defects of ALS mutants. To address these questions, we utilized a library of triple knockout (TKO) rescue cell lines with physiological expression of single Ubiquilin paralogs or disease mutants in an isogenic background. Our findings reveal that UBQLN2 has a unique ability to protect substrates from degradation and that substrate stabilization correlates with the recruitment of multiple E3 ligases, including SCF [bxo7] . We propose that E3 ligase recruitment promotes UBQLN2 phase separation, which protects substrates from proteasomal degradation. Consistent with this model, we demonstrate that ALS mutants, which were previously shown to have altered phase separation properties, also show a defect in substrate stabilization. Finally, we show that substrate stabilization appears to be a general feature of proteins that interact with the UBQLN2 Sti1 domains as amyloid precursor protein (APP) is also protected from proteasomal degradation by the formation of biomolecular condensates. This proposal unifies many existing observations in the field and presents a new paradigm for understanding Ubiquilin function in neurodegenerative disease.}, } @article {pmid40630909, year = {2025}, author = {Peller, J and Trevisan, MA and Bujia, G and Aguirre, F and Shalom, DE and Taitz, A and Henze, S and Bastola, S and Osik, J and Shewcraft, RA and Jiang, P and Schwartz, J and Heiman-Patterson, T and Sherman, ME and Wipperman, MF and Levy, O and Shou, G and Sillay, KA and Ostrow, LW and Fraenkel, E and Berry, JD and Navar Bingham, I and Roitberg, EG}, title = {Reliable monitoring of respiratory function with home spirometry in people living with amyotrophic lateral sclerosis.}, journal = {Frontiers in neurology}, volume = {16}, number = {}, pages = {1588992}, pmid = {40630909}, issn = {1664-2295}, abstract = {INTRODUCTION: Monitoring respiratory function is essential for assessing the progression of Amyotrophic Lateral Sclerosis (ALS) and planning interventions. Remote pulmonary function testing offers a promising alternative to in-clinic visits by reducing participant burden and enabling more frequent and accessible measurements.

METHODS: To evaluate the feasibility and reliability of home-based spirometry in ALS, we built on the Radcliff Study, a fully remote, longitudinal, exploratory study conducted at home by 67 people with ALS (pALS). After an initial training period, participants managed their coaching autonomously, performing spirometry independently or requesting assistance from trained personnel.

RESULTS: We demonstrate that combining flexible coaching with a predefined automatic quality control protocol yields consistent and reliable spirometry results for tracking respiratory function over time. This approach reveals that home-measured Slow Vital Capacity (SVC) and Forced Vital Capacity (FVC) evolve similarly and follow a linear trajectory throughout the study period (7.7 ± 4.0 months), in both slow and fast progressor subpopulations.

DISCUSSION: The observed linearity in respiratory trajectories supports the potential for early and accurate estimation of progression, reinforcing the feasibility of less frequent monitoring without compromising assessment precision and reducing the burden on both pALS and the healthcare system. Furthermore, our results align with reported in-clinic pulmonary tests, validating remote monitoring as a means to promote more equitable and accessible clinical trial designs.}, } @article {pmid40629851, year = {2025}, author = {Lawless, MJ and Chan, N and Patel, K and Wang, M and Colter, DC}, title = {Qualification of a electrochemiluminescence assay for the detection of human urinary neurotrophin receptor p75.}, journal = {Bioanalysis}, volume = {}, number = {}, pages = {1-9}, doi = {10.1080/17576180.2025.2529147}, pmid = {40629851}, issn = {1757-6199}, abstract = {The extracellular domain of the neurotrophin receptor p75 has been shown to be a prominent biomarker for both disease diagnosis and progression for amyotrophic lateral sclerosis. This urinary analyte may serve as a valuable fluid biomarker which greatly increases the ease of sample collection in both healthy volunteers and patients. In this paper, the method development and validation for an electrochemiluminescence assay is described. This assay completely uses commercially available reagents and can be performed using common lab equipment found in most bioanalytical labs. This method shows good accuracy and precision, high sensitivity as well as good parallelism illustrating the ability of the method to detect and report on urinary concentrations of neurotrophin receptor p75. The assay can quantitate as low as 78 pg/mL of neurotrophin receptor p75 and > 98% of healthy urine samples tested fell within the dynamic range of the assay.}, } @article {pmid40629698, year = {2025}, author = {Murdock, BJ and Park, J and Jang, DG and Zhao, B and Teener, SJ and Webber-Davis, IF and Zhao, L and Feldman, EL and Goutman, SA}, title = {In Vitro Modeling of Natural Killer Cell Cytotoxicity to Inform Personalized ALS Therapeutics.}, journal = {Annals of clinical and translational neurology}, volume = {}, number = {}, pages = {}, doi = {10.1002/acn3.70127}, pmid = {40629698}, issn = {2328-9503}, support = {//Sinai Medical Staff Foundation/ ; //Coleman Discovery Fund/ ; //Robert A. Epstein and Joan M. Chernoff-Epstein Emerging Scholar Fund/ ; //NeuroNetwork for Emerging Therapies at the University of Michigan/ ; R01TS000339/ACL/ACL HHS/United States ; R01NS120926/NH/NIH HHS/United States ; R01NS127188/NH/NIH HHS/United States ; AL200064//U.S. Department of Defense/ ; 20-IIA-431//ALS Association/ ; //Hiller and Novak Families/ ; //Peter R. Clark Fund for ALS Research/ ; //Scott L. Pranger/ ; }, abstract = {OBJECTIVE: Natural killer (NK) cells might contribute to motor neuron death in amyotrophic lateral sclerosis (ALS) through direct cytotoxicity, a process that could be inhibited with the FDA-approved JAK/STAT pathway inhibitor, tofacitinib. This study aimed to verify that tofacitinib can suppress NK cell cytotoxicity, investigate if immune cell profiles can predict responsiveness to tofacitinib, and assess the role of NK cell cytotoxicity in ALS progression.

METHODS: Primary NK cells were isolated from peripheral blood samples of ALS participants and healthy controls. NK cells were then co-cultured with target cancer cells, with or without tofacitinib, to assess their cytotoxic activity. Flow cytometry was used to generate immune profiles for each participant, based on 154 immune markers, to explore correlations with NK cell cytotoxicity and response to tofacitinib. The potential association between NK cell cytotoxicity and disease severity, as measured by the revised ALS Functional Rating Scale, was also assessed. All analyses were stratified by age and sex.

RESULTS: Tofacitinib effectively reduced the cytotoxicity of primary NK cells isolated from the blood of ALS participants (n = 80) and healthy controls (n = 71), with immune cell profiles correlating with the response to tofacitinib. However, NK cell cytotoxicity was lower in ALS participants compared to healthy controls and showed no association with ALS progression.

INTERPRETATION: These findings confirm that tofacitinib suppresses NK cell cytotoxicity, and that immune profiling may help identify treatment responder groups. However, further research is needed to fully understand the role and timing of NK cell activity in ALS pathogenesis.}, } @article {pmid40629595, year = {2025}, author = {Liu, G and Liu, N and Xu, Y and Su, F}, title = {Frontotemporal lobar degeneration and amyotrophic lateral sclerosis: A bibliometric analysis.}, journal = {Medicine}, volume = {104}, number = {27}, pages = {e43180}, pmid = {40629595}, issn = {1536-5964}, support = {202134068//Jinan City 2021 Science and Technology Innovation Development Program/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics ; *Frontotemporal Lobar Degeneration/genetics ; *Bibliometrics ; C9orf72 Protein/genetics ; DNA-Binding Proteins/genetics ; Mutation ; }, abstract = {OBJECTIVE: This study analyzes the research hotspots and future directions of frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis.

METHODS: Relevant literature was searched using the Web of Science database and analyzed using econometric tools such as CiteSpace and VOSviewer.

RESULTS: A total of 145 articles were included in this study, involving 317 research institutions in 31 countries and regions. Acta Neuropathologica is a prominent journal in terms of issuance and influence, and countries such as the United States and Japan, as well as institutions such as the University of Pennsylvania, occupy an important position in the research. The keywords cover various aspects such as disease characteristics and gene mutations; highly-cited literature focuses on TDP-43 protein and C9orf72 gene mutations. Research hotspots include TDP-43 protein disease-driven pathomechanisms, RNA-related studies, clinical manifestations of the disease and genetic studies, etc. In recent years, research focus has shifted to RNA, C9orf72 gene and so on.

CONCLUSION: To our knowledge, this study is the first econometric evaluation of the FTLD-ALS literature, and although there are limitations such as relying on the number of documents and citation relationships, and a single source of data, it provides a valuable reference for research in this field and helps to promote subsequent research.}, } @article {pmid40629407, year = {2025}, author = {Choi, Y and Chung, WS}, title = {Glial phagocytosis for synapse and toxic proteins in neurodegenerative diseases.}, journal = {Molecular neurodegeneration}, volume = {20}, number = {1}, pages = {81}, pmid = {40629407}, issn = {1750-1326}, support = {2020M3E5D9079912//Ministry of Science and ICT, South Korea/ ; 2021R1A2C3005704//Ministry of Science and ICT, South Korea/ ; 2022M3E5E8081188//Ministry of Science and ICT, South Korea/ ; IBS-R025-A1//Institute for Basic Science/ ; }, mesh = {Humans ; *Neuroglia/metabolism/pathology ; *Neurodegenerative Diseases/metabolism/pathology ; *Phagocytosis/physiology ; *Synapses/metabolism/pathology ; Animals ; }, abstract = {Glia, as resident immune and supportive cells of the central nervous system, play a critical role in maintaining brain homeostasis. One of their key homeostatic functions is phagocytic capacity in pruning synapses and removing cellular debris/protein aggregates, a process vital for synaptic plasticity and brain maintenance. However, these phagocytic functions are often dysregulated with aging and in neurodegenerative diseases (NDs), such as Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and frontotemporal dementia. This review aims to examine the phagocytic roles of glia under both physiological and pathological conditions, with a special focus on their interactions with misfolded protein aggregates, including amyloid beta, tau, alpha synuclein, prion, huntingtin, and TAR DNA-binding protein 43. We also explore the fate of ingested molecules after being phagocytosed by glia-whether they are degraded, accumulate intracellularly, or are transferred between cells-and their implications for disease progression. Finally, we review current therapeutic strategies and the potential approaches for modulating glial phagocytosis to mitigate several NDs. We believe that understanding the exact mechanisms of glial phagocytosis and clearance will serve as key elements in developing future treatments for NDs.}, } @article {pmid40629298, year = {2025}, author = {Douglas, A and McPhee, M and Fisher, F and Cheng, C and Henders, A and Ziser, L and Stout, JC and Kiernan, MC and Osborne, R and Mathers, S}, title = {Using cluster analysis to identify the health literacy strengths and challenges of people living with motor neurone disease in Australia.}, journal = {BMC health services research}, volume = {25}, number = {1}, pages = {942}, pmid = {40629298}, issn = {1472-6963}, mesh = {Humans ; *Health Literacy/statistics & numerical data ; Female ; Male ; Cluster Analysis ; *Motor Neuron Disease/psychology ; Middle Aged ; Australia ; Aged ; Surveys and Questionnaires ; Adult ; Caregivers/psychology ; Aged, 80 and over ; }, abstract = {BACKGROUND: There is growing appreciation of the role health literacy plays in population health and health care design. Health literacy encompasses an individual's capacity to manage their health and the responsiveness of the health system. Our aim was to identify the health literacy strengths and challenges in an Australian cohort living with motor neurone disease (MND), including both people living with the disease and their carers.

METHODS: This study used the Health Literacy Questionnaire and eHealth Literacy Questionnaire for health literacy assessment. Using a secure online platform, an anonymous survey was disseminated which included demographic data and clinical measurements. Descriptive statistical analysis and cluster analysis were employed to describe the sample and to identify different health literacy patterns in subgroups of people living with MND and their carers.

RESULTS: A total of 227 people participated (171 people living with MND and 56 carers). Cluster analysis generated fifteen cluster profiles for the cohort living with MND and seven cluster profiles for carers. The variability and potential significance of patterns of health literacy strengths and challenges within the MND community are described. There was extensive diversity within the sampled population, with a mix of sociodemographic backgrounds across each cluster profile.

CONCLUSIONS: The health literacy cluster profiles created from this study provide insight into the full spectrum of where the challenges and strengths exist for individuals and subgroups of people managing this fatal disease. The results from this study pave the way for generating system wide interventions that address health literacy diversity, to create more enabling health care environments for all those affected by MND.}, } @article {pmid40629037, year = {2025}, author = {Wood, H}, title = {Brain-computer interface restores naturalistic speech to a man with ALS.}, journal = {Nature reviews. Neurology}, volume = {21}, number = {8}, pages = {409}, pmid = {40629037}, issn = {1759-4766}, } @article {pmid40627876, year = {2025}, author = {Zeinab, EM and Lynn, K and Mohammad, M and Houssein, HA}, title = {Meckel's diverticulum in patient with early-onset ALS: A case report.}, journal = {International journal of surgery case reports}, volume = {133}, number = {}, pages = {111585}, pmid = {40627876}, issn = {2210-2612}, abstract = {INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a progressive motor neuron disease primarily affecting the neuromuscular system. Gastrointestinal manifestations are typically functional in nature, while mechanical obstructions are rarely reported. Meckel's diverticulum (MD), a congenital gastrointestinal anomaly, is often asymptomatic but can cause obstruction in rare adult cases.

CASE REPORT: We present the case of a 30-year-old male with early-onset ALS who presented with signs of intestinal obstruction, including severe abdominal pain, vomiting, and obstipation. Imaging revealed a closed-loop small bowel obstruction. Emergency laparotomy identified a torsed Meckel's diverticulum as the underlying cause. Surgical resection was performed, and the postoperative course was managed with tracheostomy and PEG placement due to progressive ALS-related respiratory and swallowing impairment. The patient was successfully stabilized and discharged with ongoing multidisciplinary support. The patient was discharged three weeks later in a stable condition and remains alive under multidisciplinary follow-up.

DISCUSSION: This case highlights the diagnostic challenge of distinguishing mechanical from functional gastrointestinal symptoms in patients with advanced ALS. While neurodegenerative progression often explains GI complaints in ALS, this case emphasizes the need to consider alternative etiologies, including surgical emergencies like MD-related obstruction.

CONCLUSION: Mechanical small bowel obstruction due to Meckel's diverticulum in ALS is exceedingly rare. Timely diagnosis and intervention, supported by multidisciplinary perioperative care, are critical for favorable outcomes in this high-risk population. Despite significant ALS-related comorbidities, the patient's outcome was favorable with stable discharge and ongoing respiratory and nutritional support.}, } @article {pmid40626770, year = {2025}, author = {Devrim, İ and Ergun, D and Kaçar, P and Çelebi, MY and Özer, A and Koyun, E and Koç, Y and Yıldız, ÖD and Akgül, E and Ayhan, FY and Bayram, N}, title = {The Comparison of Flushing With Prefilled Saline Syringes Versus Manually Prepared Saline Syringes on Colonization of Peripheral Intravenous Catheters in Children.}, journal = {Journal of infusion nursing : the official publication of the Infusion Nurses Society}, volume = {48}, number = {4}, pages = {247-252}, pmid = {40626770}, issn = {1539-0667}, mesh = {Humans ; *Syringes ; Child ; *Saline Solution/administration & dosage ; *Catheterization, Peripheral/adverse effects ; Turkey ; *Catheter-Related Infections/prevention & control ; *Catheters, Indwelling/microbiology ; Infusions, Intravenous ; Child, Preschool ; }, abstract = {We appreciate the study performed and described by Devrim et al, who practice at Dr. Behçet Uz Children's Diseases and Surgery Training and Research Hospital in Izmir, Turkey. This study aimed to compare the colonization rates of short-term PIVC tips between patients' catheters flushed with manually prepared saline syringes and single-use prefilled saline syringes. The practice of manually preparing saline syringes for use in flushing intravenous catheters is uncommon in many health care organizations. While many health care organizations have permanently exchanged manual flush syringe preparation for prefilled single-use saline syringes, we are respectful of professionals and organizations who serve in areas where practice is different. As noted, we appreciate Devrim et al's study and described findings. The conclusion of this study affirms and further substantiates the INS Infusion Therapy Standards of Practice described in Standard 38. Flushing and Locking. Practice Recommendation - A. Use single-dose systems (eg, single-dose vials and syringes or prefilled labeled syringes) for all VAD flushing and locking. Additional recommendations are listed in A.2. and A.3. Use commercially manufactured prefilled flush syringes (when available) to reduce the risk of catheter-associated bloodstream infection (CABSI) and device failure, save time for syringe preparation, and aid optimal flushing technique and objectives. 3. Do not use IV solution containers (eg, bags or bottles) as a source for obtaining flush solutions (see Standard 56, Compounding and Preparation of Parenteral Solutions and Medications).}, } @article {pmid40626296, year = {2025}, author = {Li, D and Wang, P and Zhang, M and Zhang, X and Yao, H and Liu, X}, title = {Advances in examination methods for adolescent idiopathic scoliosis.}, journal = {Pediatric discovery}, volume = {3}, number = {1}, pages = {e2518}, pmid = {40626296}, issn = {2835-5598}, abstract = {The purpose of this article is to provide an overview of techniques for evaluating patients with adolescent idiopathic scoliosis (AIS). It encompasses the history, clinical examinations, and diagnostic imaging methods for AIS. These methods include digital radiological examination, EOS® imaging, nuclear medicine, ultrasound, body surface topography techniques such as the Moiré pattern technique, raster stereophotography, and DIERS formetric 4D as well as computed tomography and magnetic resonance imaging (MRI). Traditionally, full-spine standing X-rays have been the standard for diagnosing AIS. High-quality clinical assessments may continue as a reference for assessing other spinal deformities. However, the new diagnostic imaging methods aim to reduce radiation exposure while maintaining image quality and practicality. Emerging technologies demonstrate strong reliability and effectiveness in diagnostic imaging of AlS. These techniques may be beneficial for diagnosing and monitoring AIS and its progression without requiring high levels of radiation exposure. The article is a search and summary of the PubMed electronic database to understand the current and future status of AIS imaging technology, which can not only help to introduce other researchers to the field but also serve as a valuable source for healthcare professionals to study existing methods, develop new ones, or select evaluation strategies.}, } @article {pmid40625857, year = {2025}, author = {Khorrami, F and Gupta, N and Zhou, X and Liang, Y and Yucel, YH}, title = {A Novel Retinal Nerve Fiber Layer Biomarker of Amyotrophic Lateral Sclerosis (ALS) Identified Using Longitudinal in vivo Ocular Imaging.}, journal = {Eye and brain}, volume = {17}, number = {}, pages = {69-79}, pmid = {40625857}, issn = {1179-2744}, abstract = {PURPOSE: Like motor neurons, retinal ganglion cells (RGCs) have long axons and high metabolic demands, making them vulnerable to disruption of axonal transport. Unlike motor neurons, the RGC axons are accessible to high-resolution non-invasive optical imaging in their intraocular portion. A non-invasive in vivo retinal imaging biomarker can be valuable for amyotrophic lateral sclerosis (ALS) diagnosis and monitoring. We aim to assess the presence of inner retinal pathology in a mouse model of ALS and its possible progression with age.

METHODS: Transgenic SOD1G93A mice (n=8, 4M/4F) and age-matched controls (n=8, 4M/4F) underwent in vivo retinal imaging with confocal scanning laser ophthalmoscopy (cSLO) coupled with optical coherence tomography (OCT) at 20 weeks of age. Another group of SOD1G93A mice (n=20, 6M/14F) and age-matched controls (n=20, 6M/14F) underwent longitudinal in vivo retinal imaging with the same device. Each retinal imaging session included infrared reflectance (IR) and blue reflectance (BR) cSLO coupled with OCT. Hyperreflective puncta located in the retinal nerve fiber layer (RNFL) were counted in a blinded fashion in ALS and control mice. The number of puncta at 20 weeks of age in ALS mice was compared with controls using Wilcoxon test. The rates of increase of puncta number were analyzed using a Generalized Linear Mixed-Effect Model (GLMM) for genotype, time, and sex.

RESULTS: IR-cSLO coupled with OCT revealed hyperreflective puncta located in the RNFL of ALS mice. IR-cSLO fundus imaging at the age of 20 weeks showed ALS mice had significantly higher number of puncta compared to controls (2.1±2.3 vs 0.5±0.8; (mean±SD), respectively, p=0.036). GLMM analysis showed both ALS mutation and age were significantly associated with the rate of increase of puncta number (p=0.000232 and p=0.000366, respectively). In addition, female ALS mice had a steeper increase of puncta compared to male ALS mice (0.21±0.04 log number puncta/week vs 0.16±0.04, respectively; p=0.037).

CONCLUSION: Our findings demonstrate distinct inner retinal nerve fiber layer pathology, detected using cSLO coupled with OCT, which worsens over time. These findings support the potential of retinal imaging as a translationally relevant, non-invasive biomarker for ALS diagnosis or disease monitoring in humans.}, } @article {pmid40625110, year = {2025}, author = {Luo, Y and Xiong, S and Ehdaie, A and Sun, H and Yang, G and Luo, D and Li, J and Wang, X and Zhang, Z and Cai, L and Liu, H and Shehata, M}, title = {Predictive Parameters for Impending Steam Pops During High-Power Short-Duration Ablation for Atrial Fibrillation.}, journal = {Pacing and clinical electrophysiology : PACE}, volume = {48}, number = {8}, pages = {836-842}, doi = {10.1111/pace.70003}, pmid = {40625110}, issn = {1540-8159}, support = {20240216//Liu Hanxiong Famous Doctor Studio of Chengdu/ ; 2024NSFSC1709//the Natural Science Foundation of Sichuan Province/ ; CSY-YN-01-2023-041//Scientific Research Project of The Third People's Hospital of Chengdu/ ; }, mesh = {Humans ; *Atrial Fibrillation/surgery ; Male ; Female ; Retrospective Studies ; *Catheter Ablation/adverse effects/methods ; Middle Aged ; *Steam ; Aged ; }, abstract = {BACKGROUND: High-power short-duration (HPSD) radiofrequency ablation (RFA) for atrial fibrillation (AF) treatment carries the risk of steam pops (SPs) due to rapid tissue heating. However, methods to predict impending SP during HPSD-RFA remain undefined.

OBJECTIVE: This study aims to establish a quantitative criterion for predicting SPs during HPSD-RFA.

METHODS: Retrospective analysis was performed on 489 patients undergoing HPSD-RFA for AF, focusing on corresponding RFA parameters in those who experienced SPs.

RESULTS: Among 1943 ablation lesions (ALs) delivered in 18 patients with SPs, 24 ALs had SP occurrence. Tip temperature, RFA duration, and ablation index were not significantly different between SP ALs and non-SP ALs. The mean contact force was significantly higher in SP ALs (12 g vs. 9, p < 0.001). All SPs adhered to the following criteria: impedance drop ≥8Ω during the first 4 s of RFA, impedance variability <5Ω within the first 4 s of RFA (24/24 vs. 79/247, p < 0.001), no events in the posterior wall of the left atrium, impedance drop ≥12Ω within 4-12 s. By halting delivery of RFA early with this finding in approximately five ALs per patient, the risk of SP complications could be significantly mitigated.

CONCLUSION: Monitoring impedance trends in the initial 4 s of HPSD-RFA can effectively predict impending SP occurrences. Automated algorithms should be developed to halt RFA delivery in this setting.}, } @article {pmid40624572, year = {2025}, author = {Pham, TK and Verber, N and Turner, MR and Malaspina, A and Collins, MO and Mead, RJ and Shaw, PJ}, title = {Glutathione oxidation in cerebrospinal fluid as a biomarker of oxidative stress in amyotrophic lateral sclerosis.}, journal = {Translational neurodegeneration}, volume = {14}, number = {1}, pages = {36}, pmid = {40624572}, issn = {2047-9158}, support = {MRC/S004920/1/MRF_/MRF_/United Kingdom ; NIHR203321//NIHR Sheffield Biomedical Research Centre/ ; }, } @article {pmid40624208, year = {2025}, author = {Tavares, M and Lúcio, MJ and Borges, J and Carriço, F and Guimarães, MJ and Drummond, M}, title = {The impact of obstructive sleep apnea and the prognostic role of level III polysomnography at the onset of amyotrophic lateral sclerosis.}, journal = {Sleep & breathing = Schlaf & Atmung}, volume = {29}, number = {4}, pages = {235}, pmid = {40624208}, issn = {1522-1709}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/complications/physiopathology/mortality ; *Polysomnography ; *Sleep Apnea, Obstructive/diagnosis/physiopathology/therapy ; Male ; Female ; Middle Aged ; Prognosis ; Cross-Sectional Studies ; Aged ; Noninvasive Ventilation ; Adult ; }, abstract = {PURPOSE: Sleep disturbances are considered an early manifestation of Amyotrophic lateral sclerosis (ALS). However, sleep-disordered breathing (SDB) in ALS remains underexplored. The primary outcome of this study is to describe the clinical, functional and polygraphic characteristics of ALS patients with baseline SDB and to compare those with and without obstructive sleep apnea (OSA) in level III polysomnography (PSG) at diagnosis. Secondary outcomes included identification of baseline factors predictive of non-invasive ventilation (NIV) initiation/death during follow-up and assessing the role of level III PSG performed at the initial clinical evaluation in ALS prognosis regarding timing to NIV initiation and death.

METHODS: A cross-sectional study was conducted on 74 patients between September 2023 and September 2024. For the primary outcome, only patients that exhibited baseline SDB were included (45 patients). The population (45) was divided into 2 groups: Group 1 (n = 26; obstructive apnea/hypopnea index ≥ 5) and Group 2 (n = 19; obstructive apnea/hypopnea index < 5). For the secondary outcomes, all 74 patients were included regardless of sleep events.

RESULTS: Patients with OSA had a higher baseline body mass index (p = 0.03) and lower nocturnal average oxygen saturation (p = 0.03). A lower forced vital capacity (p < 0.001) and higher transcutaneous carbon dioxide (p = 0.005) at baseline were predictive of timing to NIV initiation.

CONCLUSIONS: Our study highlights the importance of performing respiratory functional testing and transcutaneous carbon dioxide assessment in ALS prognosis, regarding timing to NIV initiation. Although level III PSG is vital in the diagnosis and treatment of SDB, further studies are needed to clarify its role at disease onset and identify additional potentially predictors of timing to NIV initiation/death in ALS patients.}, } @article {pmid40622763, year = {2025}, author = {Tra, NT and Kiryu-Seo, S and Kida, H and Wakatsuki, K and Tashiro, Y and Tsutsumi, M and Ataka, M and Iguchi, Y and Nemoto, T and Takahashi, R and Katsuno, M and Kiyama, H}, title = {Absence of the axon initial segment in sensory neuron enhances resistance to amyotrophic lateral sclerosis.}, journal = {Brain : a journal of neurology}, volume = {}, number = {}, pages = {}, doi = {10.1093/brain/awaf182}, pmid = {40622763}, issn = {1460-2156}, support = {21K19310//Japan Society for the Promotion of Science/ ; 23H04229//Japan Society for the Promotion of Science/ ; 24K02350//Japan Society for the Promotion of Science/ ; 23K24695//Japan Society for the Promotion of Science/ ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the selective loss of motor neurons. Proteasome dysfunction in ALS is considered to cause the accumulation of protein aggregates, which leads to motor neuron degeneration; however, the resilience of motor neurons to ALS pathology might be impaired long before the appearance of protein aggregates. Intriguingly, sensory dorsal root ganglion (DRG) neurons are not susceptible to ALS pathology despite their processes coexisting with axons of motor neurons in the same spinal nerves. Both DRG neurons and motor neurons in ALS model mice express activating transcription factor 3 (ATF3), a well-known marker of nerve injury and disease progression, suggesting that both types of neurons respond to ALS pathology. However, it remains unknown why only DRG neurons are resilient to ALS pathological damage. To address this issue, we used a nerve injury model in combination with unique injury-induced genetically engineered mice, in which genetic control with an Atf3 regulatory element enables proteasome ablation and mitochondrial visualization specifically in damaged neurons. Using the strategy, we found that DRG neurons are resistant to damage in proteasome-deficient conditions, whereas spinal motor neurons degenerate in the same conditions. This might be because DRG neurons lack the typical axon initial segment (AIS), which normally exists in mature neurons and acts as a gate for the selective transport of cargo to axons. The absence of a typical AIS in DRG neurons facilitated increased entry of mitochondria into the axon upon injury, with or without proteasome function. In contrast, damaged motor neurons lacking the proteasome failed to disassemble the AIS, which prevented increased mitochondrial influx into axons and led to energy depletion and degeneration. In the absence of the AIS, DRG neurons in the ALS mouse model are able to deliver sufficient mitochondria into the axon to prevent pathological damage. However, impaired proteasome function in ALS motor neurons results in retention of the AIS gate and failure of mitochondrial transport to axons. This is a possible reason why DRG neurons have greater resilience to ALS pathological damage compared with spinal motor neurons. Collectively, this study opens new directions for the understanding of neurodegenerative diseases at early stages of disturbed protein homeostasis.}, } @article {pmid40622676, year = {2025}, author = {Wei, Y and Li, D and Yang, R and Liu, Y and Luo, X and Zhao, W and Yang, H and Chen, Z and Shen, C and Wang, Y and Huang, Z}, title = {TIA1-mediated stress granules promote neurodegeneration by sequestering HSP70 mRNA in C9orf72 mice.}, journal = {Brain : a journal of neurology}, volume = {}, number = {}, pages = {}, doi = {10.1093/brain/awaf248}, pmid = {40622676}, issn = {1460-2156}, abstract = {Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disease with progressive loss of motor neurons in the central nervous system. Recent studies have reported that there are mutations at the T cell antigen-1 (TIA1) domain site in some ALS patients. TIA1 is a key component of stress granules (SGs), but its role and mechanism in ALS pathogenesis remain unclear. In this study, we found that TIA1 was upregulated in the motor cortex of postmortem ALS patients as well as in the motor cortex neurons of C9orf72-poly-GA mice (ALS mice). TIA1 knockout in the central nervous system (TIA1Nestin-CKO mice) alleviated motor neuron loss, neuroinflammation and motor dysfunction in C9orf72-poly-GA mice. Mechanistically, RNA-sequencing combined with the C9orf72-ALS/FTD patient (snRNA-seq) database revealed that mRNA of heat shock protein 70 (HSP70) family member genes such as HSPa1b were up-regulated in the motor cortex of TIA1Nestin-CKO ALS mice. We further found that TIA1-mediated SGs formation was increased during ALS pathogenesis, leading to HSP70 mRNA being sequestered into SGs. This reduced HSP70 expression, impairing the degradation of poly-GA aggregates by the UBQLN2-HSP70 pathway and exacerbating C9orf72-ALS progression. Taken together, these findings highlight a previously unrecognized role of TIA1-mediated SGs in promoting ALS pathogenesis by sequestering HSP70 mRNA, suggesting potential therapeutic targets for ALS treatment.}, } @article {pmid40621723, year = {2025}, author = {Anani, T and Pradat-Peyre, JF and Delbot, F and Desnuelle, C and Rolland, AS and Devos, D and , and Pradat, PF}, title = {Feature selection using metaheuristics to predict annual amyotrophic lateral sclerosis progression.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {}, number = {}, pages = {1-16}, doi = {10.1080/21678421.2025.2522399}, pmid = {40621723}, issn = {2167-9223}, abstract = {OBJECTIVE: Amyotrophic lateral sclerosis (ALS), a progressive neurodegenerative disease with no curative treatment and affecting motor neurons, leads to motor weakness, atrophy, spasticity and difficulties with speech, swallowing, and breathing. Accurately predicting disease progression and survival is crucial for optimizing patient care, intervention planning, and informed decision-making.

METHODS: Data were gathered from the PRO-ACT database (4659 patients), clinical trial data from ExonHit Therapeutics (384 patients) and the PULSE multicenter cohort aimed at identifying predictive factors of disease progression (198 patients). Machine learning (ML) techniques including logistic/linear regression (LR), K-nearest neighbors, decision tree, random forest, and light gradient boosting machine (LGBM) were applied to forecast ALS progression using ALS Functional Rating Scale (ALSFRS) scores and patient survival over one year. Models were validated using 10-fold cross-validation, while Kaplan-Meier estimates were employed to cluster patients according to their profiles. To enhance the predictive accuracy of our models, we performed feature selection using ANOVA and differential evolution (DE).

RESULTS: LR with DE achieved a balanced accuracy of 76.05% on validation (ranging from 68.6% to 79.8% per fold) and 76.33% on test data, with an AUC of 0.84. With Kaplan-Meier's estimates, we identified five distinct patient clusters (C-index = 0.8; log-rank test p value ≤0.0001). Additionally, LGBM predictions for ALSFRS progression at 3 months yielded an RMSE of 3.14 and an adjusted R[2] of 0.764.

CONCLUSION: This study showcases the potential of ML models to provide significant predictive insights in ALS, enhancing the understanding of disease dynamics and supporting patient care.}, } @article {pmid40621427, year = {2025}, author = {Gunduz, A and Akıncı, T and Kargın, OA and Tutuncu, M and Arslan, S and Uzun, N}, title = {Correlation analysis between excitability in the somatosensory cortex and structural changes in amyotrophic lateral sclerosis.}, journal = {Clinical neurophysiology practice}, volume = {10}, number = {}, pages = {202-208}, pmid = {40621427}, issn = {2467-981X}, abstract = {OBJECTIVE: We aimed to investigate the excitability of the somatosensory cortex and its relationship to structural changes in motor and sensory pathways, and motor excitability in amyotrophic lateral sclerosis (ALS).

PATIENTS AND METHOD: We included all consecutive individuals with ALS, fulfilling the "definite" or "probable" ALS criteria. We recorded surround inhibition (SI) and recovery function (RC) of somatosensory evoked potentials (SEPs), resting motor threshold, and cortical silent period (cSP), and performed volumetric analysis and diffusion tensor imaging (DTI).

RESULTS: We included 15 patients with ALS and 12 healthy individuals of similar age and sex. At the group level, the mean SEP-RC% at ISI 5 ms was higher in the ALS group than in healthy participants (all SEP-RC% at 5 ms p < 0.001). SEP-SI was lost in one-third of individuals with ALS. A negative correlation was found between the duration of the cSP and SEP-RC%, whereas no correlations were observed between SEP parameters and radiological volumetric analysis of the corticospinal tract, medial lemniscus, or cortical thickness of the precentral and postcentral gyri.

CONCLUSION: Somatosensory hyperexcitability is present in ALS, and SI is lost in a subset of patients with ALS.

SIGNIFICANCE: Somatosensory hyperexcitability correlates well with cSP but not with structural changes.}, } @article {pmid40621236, year = {2025}, author = {Rani, D and Chandan, SK and Devi, E}, title = {Motor Unit Number Estimation for Evaluating Disease Progression and Comparison With Functional Rating Scale Scores in Patients With Amyotrophic Lateral Sclerosis.}, journal = {Cureus}, volume = {17}, number = {6}, pages = {e85348}, pmid = {40621236}, issn = {2168-8184}, abstract = {Introduction Amyotrophic lateral sclerosis (ALS) is a progressive motor neuron disease characterized by degeneration of motor neurons in the brain, brainstem, and spinal cord. While the ALS Functional Rating Scale-Revised (ALSFRS-R) is commonly used to assess functional decline, its limitations highlight the need for more objective biomarkers. Motor unit number estimation (MUNE) is an electrophysiological technique that may provide a more sensitive measure of disease progression. This study aims to evaluate the utility of MUNE as a biomarker in ALS and compare its performance with ALSFRS-R. Methods This was a prospective, single-center, observational study conducted over 18 months. A total of 31 patients with definite or probable ALS, diagnosed per the Revised El Escorial Criteria, were enrolled. MUNE and ALSFRS-R assessments were performed at baseline and after six months. MUNE was calculated using the multi-point incremental method in the upper extremity. Data were analyzed using paired t-tests and Pearson's correlation coefficients. Subgroup analyses by age, sex, and symptom onset site were also conducted. Results Both MUNE and ALSFRS-R scores declined significantly over six months. The mean MUNE decreased from 16.36 ± 5.22 to 13.37 ± 4.96 (p < 0.0001), while the ALSFRS-R score declined from 42.06 ± 3.24 to 36.72 ± 4.89 (p < 0.0001). The mean rate of decline was significantly greater for MUNE (23.6 ± 15.31) than for ALSFRS-R (13.91 ± 8.18; p = 0.001). No significant associations were observed between MUNE and patient age, sex, or site of symptom onset. Correlation between MUNE and ALSFRS-R was weak at both time points. Conclusions MUNE demonstrated a significantly greater rate of decline than ALSFRS-R, suggesting higher sensitivity to motor neuron loss over time. These findings support using MUNE as a reliable and objective biomarker for monitoring disease progression in ALS. Incorporating MUNE into clinical practice and research may improve prognostication, enable earlier therapeutic intervention, and enhance patient stratification in clinical trials. Further large-scale studies are needed to validate its routine use.}, } @article {pmid40621104, year = {2025}, author = {Rosene, MJ and Benitez, BA}, title = {Cysteine string protein α and a link between rare and common neurodegenerative dementias.}, journal = {NPJ dementia}, volume = {1}, number = {1}, pages = {15}, pmid = {40621104}, issn = {3005-1940}, abstract = {The maintenance of protein homeostasis and overall protein quality control dysfunction are associated with dementia. Cysteine string protein α (CSPα) is an endolysosomal cochaperone that facilitates the fusion of secretory and synaptic vesicles to the cell membrane. CSPα interacts with multiple proteins related to the proteostasis network and exocytic pathways and is often dysfunctional in synaptopathies. Since the initial discovery of CSPα 30 years ago, subsequent research has demonstrated a protective role of CSPα, especially in synaptic maintenance. However, the discovery of heterozygous CSPα mutations in 2011 causing adult-onset neuronal ceroid lipofuscinosis (ANCL) shifted the back-then prevalent dogma of unique synaptic function to include an endolysosomal role for CSPα. Recently, CSPα has been involved in the exocytosis of aggregate-prone proteins through either the misfolding-associated protein secretion (MAPS) or unconventional secretory pathways linking the molecular mechanism of rare and common neurodegenerative diseases. Here, we propose a novel molecular and pathophysiological model of CSPα-associated dementia, outline the increasing evidence of a broader role of CSPα in neurodegeneration, propose the role of CSPα in the synaptic secretion of neurodegenerative-associated proteins, and discuss the modulation of CSPα as a molecular target for common dementias.}, } @article {pmid40620778, year = {2025}, author = {Pavlenko, TA and Chesnokova, NB and Beznos, OV and Shikareva, NN and Nodel, MR and Shevtsova, KV and Panina, UV and Shteinberg, DA and Kukharskaya, OA and Sukhanova, IS and Pukaeva, NE and Kukharsky, MS and Ovchinnikov, RK}, title = {Superoxide dismutase activity in tear fluid and blood of patients and mouse model of amyotrophic lateral sclerosis: a pilot study.}, journal = {PeerJ}, volume = {13}, number = {}, pages = {e19623}, pmid = {40620778}, issn = {2167-8359}, mesh = {*Amyotrophic Lateral Sclerosis/enzymology/blood ; Animals ; Humans ; Pilot Projects ; *Tears/enzymology ; Mice ; Disease Models, Animal ; Male ; Middle Aged ; Mice, Transgenic ; Female ; Superoxide Dismutase-1/blood/metabolism ; *Superoxide Dismutase/blood/metabolism ; Aged ; Adult ; RNA-Binding Protein FUS/genetics/metabolism ; Biomarkers/blood ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a severe neurodegenerative disease characterized by progressive degeneration of motor neurons and skeletal muscle atrophy. The heterogeneity of clinical symptoms and the lack of reliable biomarkers hamper diagnostics of ALS. The dysfunction of superoxide dismutase 1 (SOD1) protein is considered one of the molecular mechanisms underlying ALS pathology. We measured total SOD activity in the tear fluid and blood serum of ALS patients, healthy volunteers, and in the ALS mouse model, harboring the human truncated form of fused in sarcoma (FUS) protein-FUS (1-359). The average SOD activity in tear fluid did not differ between ALS patients and the control group. However, an increased proportion of patients with low SOD activity in tear fluid was observed compared to the control group. In contrast, SOD activity in blood serum was higher in the ALS group. Transgenic FUS (1-359) mice showed decreased SOD activity in tear fluid at both presymptomatic and symptomatic stages of ALS. SOD activity in blood serum did not differ between transgenic and control animals. These findings suggest that changes in SOD activity in the tear fluid of ALS patients and transgenic FUS (1-359) mice reflect local metabolic disturbances in the eyes associated with ALS.}, } @article {pmid40620684, year = {2025}, author = {Chen, P and Wang, F and Ling, B and Zhu, Y and Lin, H and Huang, J and Wang, X}, title = {Mesenchymal Stem Cell-Derived Extracellular Vesicles: Emerging Therapies for Neurodegenerative Diseases.}, journal = {International journal of nanomedicine}, volume = {20}, number = {}, pages = {8547-8565}, pmid = {40620684}, issn = {1178-2013}, mesh = {Humans ; *Neurodegenerative Diseases/therapy ; *Mesenchymal Stem Cells/cytology ; *Extracellular Vesicles/metabolism/transplantation ; Biomarkers/metabolism ; *Mesenchymal Stem Cell Transplantation/methods ; }, abstract = {Neurodegenerative diseases are a group of chronic diseases characterized by a gradual loss of neurons that worsens over time and dysfunction. These diseases are extremely harmful, not only affecting the physical health of the patients, but also having a serious impact on their quality of life. They mainly include Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), Amyotrophic lateral sclerosis (ALS), etc. Their pathogenesis is complex, and it is difficult for the existing treatments to effectively slow down the progression of the disease. In recent years, Mesenchymal Stem Cells (MSCs) have received widespread attention for their anti-inflammatory, immunomodulatory and neuroprotective properties. In this context, MSC-derived Extracellular Vesicles (MSC-EVs) have demonstrated unique therapeutic potential as a cell-free therapeutic strategy. MSC-EVs are rich in bioactive substances such as proteins, lipids, mRNAs and miRNAs, which can pass through the blood-brain barrier and be targeted to the diseased area to regulate neuronal survival, synaptic plasticity and neuroinflammatory responses. In addition, compared with stem cell therapy, MSC-EVs have the advantages of low immunogenicity, easy storage and transportation, and avoiding ethical controversies. However, their clinical application still faces challenges: standardized isolation and purification techniques have not been unified, vesicle loading efficiency and targeting need to be further optimized, and long-term safety needs to be systematically evaluated. This review focuses on the role of MSC-EVs in the development of neurological diseases and explores their possible dual roles, both favorable and unfavorable, in the context of neurological diseases. In addition, this review provides a review of current studies on EVs as potential biomarkers for the diagnosis and treatment of neurodegenerative diseases and provides a comprehensive review of the prospects and challenges of MSC-EVs in clinical applications.}, } @article {pmid40619865, year = {2025}, author = {Vogel, E}, title = {Value-Scapes of Death: Livestock Veterinarians and the Regulation of Farm Animal Life in the Netherlands.}, journal = {Medical anthropology}, volume = {}, number = {}, pages = {1-14}, doi = {10.1080/01459740.2025.2527089}, pmid = {40619865}, issn = {1545-5882}, abstract = {This article examines the crucial role of veterinarians in making animal death valuable, enabling productive life, and managing uncontrolled dying. Based on ethnographic fieldwork on dairy farms in the Netherlands, and considering veterinarians as gatekeepers of the food chain, health practitioners, and governance actors, I articulate the "value-scapes" of food production that shape which animals die, when, and how, and whether death is desirable, a waste, or a warning. Veterinization here narrates how veterinary expertise is shaped by diverse societal concerns like food security, public health, animal welfare, and ecological sustainability, and knotted into shifting and multifaceted formations of Dutch-European animality.}, } @article {pmid40619836, year = {2025}, author = {Feng, Y and Wang, X and Chen, C and Wang, D and Hou, C and Wang, Y and Hu, H and Chen, P and Qin, L and Wan, Q and Yao, X and He, ML}, title = {Carbon Quantum Dots Assisted Virus Tracking: From Skin to Brain.}, journal = {Advanced materials (Deerfield Beach, Fla.)}, volume = {}, number = {}, pages = {e2508464}, doi = {10.1002/adma.202508464}, pmid = {40619836}, issn = {1521-4095}, support = {11104020//RGC General Research Fund of Hong Kong Special Administrative Region/ ; C1018-23G//Collaborative Research Fund/ ; 7005874//Strategic funds/ ; 7020032//Strategic funds/ ; 9680149//Strategic funds/ ; //City University of Hong Kong/ ; JCYJ20240813153107010//Shenzhen Basic Research Program/ ; 9229501-14-YX//IDM Project/ ; 2025A1515011479//Basic and Applied Basic Research Foundation of Guangdong Province/ ; }, abstract = {Incurable infection by herpes simplex virus 1 (HSV-1) can cause severe encephalitis and neurodegenerative diseases, e.g., Alzheimer's disease (AD) and amyotrophic lateral sclerosis. How HSV-1 reaches the brain from the initial infection site remains inconclusive. Here, an innovative approach combining carbon quantum dots (CQDs) with dissolving microneedles (dMN) for real-time tracking of HSV-1 from skin to brain is presented. Upon application, CQDs-HSV-1 is released from the dMN through the swelling of interstitial fluid (ISF) in skin and subsequently monitored by living imaging. Remarkably, it is observed that HSV-1 preferentially infects peripheral skin nerves, almost all viruses directly enter to brain via the spinal cord within 10-30 min, while few viruses enter the brain through the bloodstream via tail vein injection at the same time. Spinal cord injury (SCI) significantly delays the HSV-1 transport from skin to brain but has no effect on the virus's travel from blood to brain. In a microfluid system, HSV-1 shows preferential neurite infection, then transports to the cell body of differentiated SH-SY5Y cells, highlighting the viral traffic process in neurons. The integration of CQDs-virus labelling technology and dMN delivery model presents a promising tool for investigating the in vivo transport routes of neurotropic viruses with initial skin infections.}, } @article {pmid40619651, year = {2025}, author = {Chauhan, S and Maan, P and Panghal, A}, title = {TDP-43 Proteinopathies in ALS and FTLD: Mechanistic Insights and Therapeutic Approaches.}, journal = {CNS & neurological disorders drug targets}, volume = {}, number = {}, pages = {}, doi = {10.2174/0118715273374466250617085832}, pmid = {40619651}, issn = {1996-3181}, abstract = {TAR DNA-binding protein 43 (TDP-43) is a vital RNA/DNA-binding protein involved in RNA metabolism, playing a key role in the pathogenesis of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Approximately 97% of sporadic ALS (sALS), familial ALS (fALS) and FTLD cases are associated with pathological inclusions of hyperphosphorylated and ubiquitinated TDP-43 and genetic mutations in TAR DNA binding protein (TARDBP). Besides TARDBP, mutations in other genes such as C9ORF72, SOD1, FUS, and NEK1 are also linked to other fALS cases. Cytoplasmic mislocalization, aberrant post-translational modifications, and amyloid- like aggregation characterize TDP-43 pathology. These pathological changes impair essential cellular processes, including gene expression, mRNA stability, and RNA metabolism. Mechanisms of TDP-43-induced toxicity include disruption of endocytosis, mitochondrial dysfunction, and progressive cellular damage. Additionally, liquid-liquid phase separation (LLPS) and prion-like propagation are emerging as central features of its pathological spread. This review summarizes advances in understanding TDP-43's physiological functions and pathological mechanisms in ALS and FTLD. It highlights key processes underlying TDP-43 toxicity, such as aggregation, selective neuronal vulnerability, and regional susceptibility. Finally, this review summarizes evolving therapeutic strategies aimed at mitigating TDP-43-related toxicity through disaggregation, targeting mislocalization, and addressing upstream dysfunctions and challenges faced in the development of effective therapies for ALS and FTLD.}, } @article {pmid40618857, year = {2025}, author = {Balbi, M and Torazza, C and Altosole, T and Ravera, S and Farinini, E and Tessitore, S and Bacchetti, F and Rosso, F and Musante, I and Alfei, S and Cerminara, M and Puliti, A and Filaci, G and Fenoglio, D and Leardi, R and Fedele, E and Bonanno, G and Milanese, M and Bonifacino, T}, title = {The complex phenotype and function of spinal cord microglia during ALS progression and the impact of metabotropic glutamate receptor type 5 down-regulation in SOD1[G93A] mice.}, journal = {Neurobiology of disease}, volume = {213}, number = {}, pages = {107017}, doi = {10.1016/j.nbd.2025.107017}, pmid = {40618857}, issn = {1095-953X}, mesh = {Animals ; *Amyotrophic Lateral Sclerosis/metabolism/pathology/genetics ; *Microglia/metabolism/pathology ; *Spinal Cord/metabolism/pathology ; *Receptor, Metabotropic Glutamate 5/metabolism/genetics ; Mice, Transgenic ; Mice ; Disease Progression ; Superoxide Dismutase-1/genetics/metabolism ; Phenotype ; Down-Regulation ; Disease Models, Animal ; Mice, Inbred C57BL ; }, abstract = {Over the last few decades, scientists' attention has shifted from neuronal to non-neuronal cells to explain the mechanisms at the basis of neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS). ALS is a multifactorial and multicellular disease in which microglia have a central role, during disease progression. We previously demonstrated that metabotropic glutamate receptor 5 (mGluR5) is dysfunctional in the spinal cord of the SOD1[G93A] ALS mice, and its in-vivo genetic or pharmacological dampening ameliorates disease outcome and astrocyte and microglia reactivity. Here, we studied the expression of typical phenotype-related markers during the disease progression in spinal cord microglia cells acutely isolated from early asymptomatic and late symptomatic SOD1[G93A] ALS mice. Moreover, we investigated whether reducing mGluR5 affected the microglia phenotype and function. In contrast to what we previously observed in astrocytes, mGluR5 expression decreased during disease progression in microglia acutely isolated from adult SOD1[G93A] mice. In-vivo genetic mGluR5 downregulation did not affect microglia phenotype-relevant markers, which evidenced a unique expression distribution. Conversely, mGluR5 reduction ameliorated redox balance and bioenergetics of adult microglia. Microglia cultured from the spinal cord of SOD1[G93A] pups showed that in-vitro mGluR5 pharmacological manipulation by the negative allosteric modulator CTEP partially modified their bioenergetic and oxidative status. Overall, our results suggest that mGluR5 manipulation ameliorates microglia phenotype and function in ALS by both direct and indirect mechanisms. Consequently, we hypothesised that the improvement of microglia reactive status by in-vivo mGluR5 downregulation or CTEP pharmacological modulation is supported by ameliorated bioenergetic metabolism, and the indirect astrocyte's phenotype change that promotes an improvement of the surrounding environment.}, } @article {pmid40618376, year = {2025}, author = {Scirocco, E and Allen, MD and Giacomelli, E and Ajroud-Driss, S and Andrews, J and Banack, S and Bede, P and Benatar, M and Cheung, K and Corcia, P and de Carvalho, M and Elman, L and Fink, JK and Genge, A and Hardiman, O and Harms, M and Heitzman, D and Jang, G and Kano, O and Kiernan, MC and Lee, I and Ludolph, A and Mehta, P and Ozdinler, H and Rezania, K and Schito, P and Sherman, AV and Silani, V and Sorenson, E and Turner, MR and Van Den Berg, L and Mitsumoto, H and Paganoni, S}, title = {Toward therapeutic trials in primary lateral sclerosis.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {}, number = {}, pages = {1-8}, doi = {10.1080/21678421.2025.2527123}, pmid = {40618376}, issn = {2167-9223}, abstract = {Primary lateral sclerosis (PLS) is a rare neurodegenerative disorder primarily affecting the upper motor neurons. People living with PLS experience progressive physical and communication disability, which typically evolves slowly over several years. In contrast to amyotrophic lateral sclerosis (ALS), life expectancy is anticipated to be normal. Disease-modifying medications are not available and PLS drug development has been challenging. This review considers recent advances and ongoing initiatives aimed at promoting clinical trial readiness for PLS. Ongoing clinical research efforts include patient registries and biorepositories, natural history studies, outcome measure validation, and biomarker development. These international collaborative efforts are essential for developing the first therapeutic trials for people living with PLS.}, } @article {pmid40618341, year = {2025}, author = {Asghari Jafari, E and Arabi, M and Bereimipour, A}, title = {Integrated genomic and molecular insights into astrocyte- and oligodendrocyte-derived amyotrophic lateral sclerosis: focus on miRNAs and extracellular vesicles.}, journal = {Cellular and molecular biology (Noisy-le-Grand, France)}, volume = {71}, number = {6}, pages = {1-8}, doi = {10.14715/cmb/2025.71.6.1}, pmid = {40618341}, issn = {1165-158X}, mesh = {*Amyotrophic Lateral Sclerosis/genetics/pathology/metabolism ; *MicroRNAs/genetics/metabolism ; Humans ; *Astrocytes/metabolism/pathology ; *Oligodendroglia/metabolism/pathology ; *Extracellular Vesicles/metabolism/genetics ; Computational Biology/methods ; *Genomics/methods ; Signal Transduction ; }, abstract = {Motor neurons in the brain and spinal cord begin to die off in Amyotrophic lateral sclerosis (ALS), a disease that can be fatal. Molecular pathways in neurological disease, especially ALS, remain a challenge in the medical sciences. In this disease, a disorder in both astrocytes and oligodendrocytes can cause the disease to progress. This study aimed to investigate the molecular mechanisms and find key elements between these two cells in ALS with a bioinformatics perspective. In this study, using integrated and continuous bioinformatics analytics by various tools and databases, we investigated genes, protein products, and miRNAs between astrocytes and oligodendrocytes. The obtained data were involved in the Cellular senescence, actin cytoskeleton, and cell cycle signaling pathways. Then, after careful evaluation of the information, TP53, MDM2, KRAS, PTPRC, and GSK proteins were candidates, which are regulated by hsa-miR-564, hsa-miR-496-5p, hsa-miR-324-5p, hsa-miR-296-5p, and hsa-miR-4258-3p miRNAs. Finally, the four genes had a more robust and better relationship in this study between astrocyte and oligodendrocyte-derived ALS.}, } @article {pmid40618260, year = {2025}, author = {Zhang, J and Ma, W and Liu, R and Li, X and Yuan, Z and Cheng, J}, title = {Neuromodulatory role and therapeutic potential of N6-methyladenosine RNA methylation in neurodegenerative diseases.}, journal = {Neural regeneration research}, volume = {}, number = {}, pages = {}, doi = {10.4103/NRR.NRR-D-24-01648}, pmid = {40618260}, issn = {1673-5374}, abstract = {N6-methyladenosine RNA methylation, an essential post-transcriptional modification, dynamically regulates RNA metabolism and plays a crucial role in neuronal function. Growing evidence suggests that dysregulated N6-methyladenosine modification contributes to the pathogenesis of neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, multiple sclerosis, and amyotrophic lateral sclerosis. However, the precise mechanisms by which N6-methyladenosine modification influences these conditions remain unclear. This review summarizes the role of m6A modification and its associated regulators in neurodegeneration, focusing on their involvement in key pathological processes. In Alzheimer's disease, m6A modification contributes to synaptic dysfunction, mitochondrial damage, and neuronal apoptosis. Evidence from APP/PS1, 5XFAD, tau transgenic, and Drosophila models demonstrates that regulators such as METTL3 and FTO influence Alzheimer's disease progression through neuroinflammation, circRNA dysregulation, and autophagy-related mechanisms. In Parkinson's disease, altered N6-methyladenosine regulator expression affects dopaminergic neuron survival and stress responses by modulating mRNA stability and autophagy-related lncRNAs. In multiple sclerosis and amyotrophic lateral sclerosis, N6-methyladenosine affects immune activation, myelin repair, and the regulation of disease-associated genes such as TDP- 43. Beyond N6-methyladenosine, other RNA methylation modifications-such as m1A, m5C, m7G, uracil, and pseudouridine-are implicated in neurodegenerative diseases through their regulation of mitochondrial function, RNA metabolism, and neuronal stress responses. Additionally, N6- methyladenosine exhibits cell type-specific functions: in microglia, it regulates inflammatory activation and phagocytic function; in astrocytes, it modulates metabolic homeostasis and glutamate-associated neurotoxicity; in neurons, it affects synaptic function and neurodegeneration-related gene expression; and in adult neural stem cells, it controls differentiation, neurogenesis, and cognitive plasticity. Recently, several small-molecule inhibitors targeting METTL3 or FTO have been developed to modulate N6-methyladenosine modification, providing new opportunities for disease intervention, with the targeting of N6-methyladenosine-related pathways emerging as a promising therapeutic strategy. However, challenges persist in optimizing the specificity and delivery of these therapeutic approaches.}, } @article {pmid40618254, year = {2025}, author = {Singh, A and Subramanian, M and Singh, A}, title = {MicroRNAs in the pathogenesis of neurodegenerative disorders: Potential as therapeutic targets.}, journal = {Neural regeneration research}, volume = {}, number = {}, pages = {}, doi = {10.4103/NRR.NRR-D-25-00402}, pmid = {40618254}, issn = {1673-5374}, abstract = {Neurodegenerative diseases (neurodegenerative disorders) are marked by the progressive degeneration of the structure and function of the central nervous system. They may result in the deterioration of cognitive, motor, and functional abilities. Diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis represent some of the most prominent examples of neurodegenerative disorders. Despite scientific advancement in understanding disease pathology and prognosis, the therapeutic strategies available for management remain limited. In recent years, microRNAs, small non-coding RNA molecules, have emerged as key players in the pathogenesis of neurodegenerative disorders. Therefore, understanding how these microRNAs affect disease pathology and pathway signaling is essential, and may open microRNAs as new avenues for potential therapeutic intervention. This review explores the role of microRNAs in various neurodegenerative diseases, discuss how microRNAs affect signaling pathways, and examine the potential of microRNAs as therapeutic targets.}, } @article {pmid40617623, year = {2025}, author = {Faure-de Baets, J and Besnard, J and Cassereau, J and Emmelin, E and Allain, P}, title = {Assessment of social cognition in patients with amyotrophic lateral sclerosis: protocol for a cross-sectional comparative study at Angers University Hospita.}, journal = {BMJ open}, volume = {15}, number = {7}, pages = {e097543}, pmid = {40617623}, issn = {2044-6055}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/psychology ; Cross-Sectional Studies ; *Social Cognition ; Neuropsychological Tests ; Male ; Female ; Case-Control Studies ; Research Design ; Middle Aged ; Cognition ; }, abstract = {INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder primarily affecting motor neurons. In addition to motor impairments, ALS frequently involves cognitive and behavioural disturbances, including deficits in social cognition, which can impact interpersonal interactions and decision-making. Despite increasing recognition of these impairments, existing assessment tools often rely on static stimuli, limiting their ecological validity.

METHODS AND ANALYSIS: This cross-sectional, single-centre study aims to assess social cognition abilities in patients with ALS compared with healthy controls using a combination of dynamic and static neuropsychological tools. The primary outcome measure will be performance on the Movie for the Assessment of Social Cognition, an ecologically valid test evaluating theory of mind. Secondary outcomes will include emotion recognition (static and dynamic tasks: Ekman Faces and French Emotion Evaluation Test), mood assessments (Hospital Anxiety and Depression Scale) and clinical variables such as disease severity (ALS Functional Rating Scale-Revised), cognitive function (Edinburgh Cognitive and Behavioural Screen, Mini-Mental State Examination) and disease staging (King's ALS Clinical Staging System). A total of 74 participants (37 patients with ALS and 37 matched healthy controls) will be recruited. Group differences will be analysed using analysis of variance, while regression models will explore associations between social cognitive deficits and clinical markers of ALS progression.

ETHICS AND DISSEMINATION: This study has been approved by the French Ethics Committee (CPP) Ouest I under reference 2020-A01213-36. Data collection and processing comply with French and European data protection regulations (GDPR, Loi Informatique et Libertés). Findings will be disseminated through peer-reviewed journals and scientific conferences and will contribute to improving neuropsychological assessment methods for ALS.

TRIAL REGISTRATION NUMBER: NCT04406675.}, } @article {pmid40616089, year = {2025}, author = {Al Kamaly, O and Al-Khateeb, LA and Halim, MK and Katamesh, NS and Magdy, G and Abbas, AEF}, title = {D-optimal candexch algorithm-enhanced machine learning UV-spectrophotometry for five-analyte determination in novel anti-glaucoma formulations and ocular fluids: four-color sustainability framework with NQS assessment and UN-SDG integration.}, journal = {BMC chemistry}, volume = {19}, number = {1}, pages = {198}, pmid = {40616089}, issn = {2661-801X}, support = {PNURSP2025R917//Princess Nourah Bint Abdulrahman University/ ; }, abstract = {The novel anti-glaucoma ophthalmic preparation containing latanoprost, netarsudil, and benzalkonium chloride has posed a significant challenge due to its complexity and the lack of environmentally sustainable quantification methods, with only a single published method available for its quantification that lacks environmental consideration. This study aims to address this crucial gap by presenting a novel and sustainable approach using machine learning-enhanced UV-spectrophotometric chemometric models for the concurrent quantification of latanoprost, netarsudil, benzalkonium chloride, and two related compounds in ophthalmic preparations and aqueous humour. A strategic multi-level, multi-factor experimental design creates a 25-mixture calibration set for four models (PLS, GA-PLS, PCR, and MCR-ALS). The key novelty was using the D-optimal design generated by MATLAB's candexch algorithm to construct a robust validation set, overcoming random data splitting limitations in machine learning chemometric methods and ensuring unbiased evaluation across concentrations. The optimized MCR-ALS model outperforms in predictive ability, with recovery percentages of 98-102%, low root mean square errors of calibration and prediction, favorable bias-corrected mean square error of prediction, relative root mean square error within acceptable limits, and adequate limits of detection for pharmaceutical analysis. The Greenness Index Spider Charts and the Green Solvents Selection Tool were applied to replace hazardous solvents. A total of seven advanced evaluation tools were employed to assess the method's greenness, blueness, violetness, and whiteness, highlighting its eco-friendly profile, practical relevance, and innovation potential. Additionally, the method's environmental and societal benefits were further validated using the Need, Quality, Sustainability (NQS) index. Overall, this machine learning-based framework contributes meaningfully to ten United Nations Sustainable Development Goals (UN-SDGs), underscoring its value for future-oriented pharmaceutical research.}, } @article {pmid40616030, year = {2025}, author = {Kikkawa, Y and McIntosh, L and Mavin, TJ and Barlow, M and O'Brien, L and Hodge, S and Janssens, S}, title = {Developing a learning tool for advanced life support and resuscitation: Performance Reflection Model for Resuscitation (PRM-Resus).}, journal = {BMC medical education}, volume = {25}, number = {1}, pages = {1001}, pmid = {40616030}, issn = {1472-6920}, support = {AQIRF100-2020-CV//Advance Queensland/ ; 2615//Betty McGrath Mater Research/ ; }, mesh = {Humans ; *Clinical Competence ; *Simulation Training/methods ; *Resuscitation/education ; *Advanced Cardiac Life Support/education ; Models, Educational ; Video Recording ; }, abstract = {BACKGROUND: Acquiring proficiency in advanced life support (ALS) can pose challenges for novice learners. Simulation-based training (SBT) is widely used to address this, offering learners opportunities to practise and receive feedback during debriefing. However, existing performance tools often lack the clarity, behavioural specificity, and educational scaffolding required to support deep reflective learning. This study aimed to develop and evaluate the Performance Reflection Model for Resuscitation (PRM-Resus) and to integrate it with the ALS Team Model and structured video exemplars as a comprehensive learning package to enhance ALS training.

METHODS: The study involved four phases. Phase 1 created the ALS Team Model to clarify individual roles. Phase 2 focused on co-designing PRM-Resus, using team expertise and the Team Model to create behaviourally anchored performance descriptors. In Phase 3, video scenarios were produced to represent ALS team performance at varying proficiency levels. Phase 4 evaluated the PRM-Resus through expert think-aloud studies. Qualitative content analysis was used alongside Cronbach's alpha to assess internal consistency and its use for SBT.

RESULTS: The PRM-Resus comprises four domains-clinical skills, clinical knowledge, team management, and leadership-each defined by behavioural descriptors across three performance levels. The participating experts endorsed the tool's clarity, structure, and educational value for novice learners. Internal consistency was high (α > 0.95). When used alongside the ALS Team Model and video exemplars, PRM-Resus facilitated deeper performance analysis, which had potential for enhancing post-simulation reflection and supporting faculty development.

CONCLUSIONS: This study presents a novel, interdisciplinary framework that integrates PRM-Resus, the ALS Team Model, and video exemplars to support reflective learning in ALS simulation. Together, these tools help novice learners build a concrete understanding of effective team performance and enable educators to deliver more structured feedback. Further research should explore its impact on learner development and potential translation into improved clinical outcomes.}, } @article {pmid40615926, year = {2025}, author = {Chen, C and Zhu, S and Zheng, Z and Ding, X and Shi, W and Xia, T and Gu, X}, title = {A Genome-wide study on the genetic and causal effects of smoking in neurodegeneration.}, journal = {Journal of translational medicine}, volume = {23}, number = {1}, pages = {743}, pmid = {40615926}, issn = {1479-5876}, support = {82171193//Natural Science Foundation for Young Scientists of Shanxi Province/ ; ZDXK202232//Jiangsu Provincial Medical Key Discipline/ ; }, mesh = {Humans ; *Genome-Wide Association Study ; *Smoking/adverse effects/genetics ; *Genetic Predisposition to Disease ; *Neurodegenerative Diseases/genetics ; Mendelian Randomization Analysis ; Parkinson Disease/genetics ; Risk Factors ; Alzheimer Disease/genetics ; Causality ; Linkage Disequilibrium/genetics ; Polymorphism, Single Nucleotide/genetics ; }, abstract = {BACKGROUND: Smoking represents the largest preventable risk factor for human health, yet previous studies have failed to establish conclusive evidence regarding the causal relationship between smoking and neurodegenerative diseases. This study employs genetic correlation and Mendelian randomization analyses to investigate the potential association between smoking and neurodegenerative disorders.

METHODS: This study analyzed summary data from genome-wide association studies (GWAS) on smoking and neurodegenerative diseases. Genetic correlations were evaluated using linkage disequilibrium score regression (LDSC), and causal relationships were assessed through multiple Mendelian randomization methods including inverse-variance weighted (IVW), MR-Egger regression, weighted median (WME), weighted mode (WM), and simple mode (SM). sensitivity analyses were performed to examine heterogeneity, horizontal pleiotropy, and conduct leave-one-out analysis.

RESULTS: whether an individual had ever smoked regularly (SmkInit) is positively correlated with an increased risk of Alzheimer's disease (AD) (rg = 0.134, P = 2.74 × 10⁻⁸) and negatively correlated with the risk of Parkinson's disease (PD) (rg = - 0.100, P = 1.8 × 10⁻[4]). cigarettes per day (CigDay) are associated with a higher risk of AD (rg = 0.162, P = 4.26 × 10⁻⁵). Smoking cessation (SmkCes) is linked to an elevated risk of AD (rg = 0.1466, P = 1.5 × 10⁻[4]), whereas age of initiation of regular smoking (AgeSmk) is negatively correlated with AD risk (rg = - 0.181, P = 8.63 × 10⁻⁶) but positively correlated with PD risk (rg = 0.170, P = 2.0 × 10⁻[4]). Results suggest that both SmkInit and CigDay significantly increase AD risk (OR = 1.030, P = 1.74 × 10⁻⁴; OR = 1.022, P = 5.04 × 10⁻⁴), while SmkCes is associated with a reduced risk of PD (OR = 0.638, P = 1.91 × 10⁻⁶) and amyotrophic lateral sclerosis (ALS) (OR = 0.830, P = 5.29 × 10⁻⁶).

CONCLUSION: This study identified significant genetic associations between smoking behaviors and neurodegenerative diseases. CigDay and SmkInit increased AD risk, while SmkCes was linked to reduced risks of PD and ALS.}, } @article {pmid40614949, year = {2025}, author = {Sarkar, SK and Gubert, C and Hannan, AJ}, title = {The microbiota-inflammasome-brain axis as a pathogenic mediator of neurodegenerative disorders.}, journal = {Neuroscience and biobehavioral reviews}, volume = {176}, number = {}, pages = {106276}, doi = {10.1016/j.neubiorev.2025.106276}, pmid = {40614949}, issn = {1873-7528}, abstract = {In various neurodegenerative disorders, inflammation and associated inflammasome activation play an important role. The most prevalent and extensively researched inflammasomes are NLRP3 inflammasomes, which are triggered by pathogens or danger signals mediating inflammatory reaction. Extracellular ATP also activates NLRP3 by stimulating the purinergic receptor P2X7 (P2X7R). Central and peripheral cells, including those in the gut, have been shown to have activated inflammasomes during pathological changes co-occurring with inflammation in various neurodegenerative disorders. Gut injury or dysfunction is increasingly recognised as one of the peripheral pathogenic characteristics of many neurodegenerative disorders, and has been found to associate with changes in gut microbes. In this article, we review data from preclinical and clinical studies regarding the involvement of the NLRP3 inflammasome and the purinergic receptor P2X7R in the pathophysiology of major CNS disorders involving neurodegeneration, including Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), Huntington's disease (HD), and the most common form of motor neuron disease, amyotrophic lateral sclerosis (ALS). We also scrutinise the relationship of the NLRP3 inflammasome to intestinal microbiota alterations in these diseases. Both the NLRP3 inflammasome and P2X7R have been shown to play important roles in the pathogenesis and progression of these neurodegenerative diseases. However, most studies have focused on central nervous system (CNS) pathology, particularly within the brain, with comparatively less attention given to their contribution to gut pathology. Additionally, changes in the microbial ecosystems of the intestine have also been implicated in these disorders. However, the association between gut microbiota alterations and inflammasome activity in the pathology of these neurodegenerative disorders remains poorly understood. Therefore, further investigation is urgently needed to explore the microbiota-inflammasome-brain axis in these neurodegenerative conditions, in order to better understand their contribution to disease pathogenesis and progression, and identify novel therapeutic targets and new approaches to prevention and treatment.}, } @article {pmid40614636, year = {2025}, author = {Hirayama, T and Nagasawa, J and Shibukawa, M and Morioka, H and Yokoyama, T and Tsuda, H and Bokuda, K and Ogino, M and Takao, H and Morita, M and Takahashi, Y and Nakamura, R and Atsuta, N and Urushitani, M and Yamanaka, K and Izumi, Y and Kano, O}, title = {Survey research on the awareness and usage of accessibility features of information and communication technology devices among patients with amyotrophic lateral sclerosis.}, journal = {Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia}, volume = {139}, number = {}, pages = {111434}, doi = {10.1016/j.jocn.2025.111434}, pmid = {40614636}, issn = {1532-2653}, abstract = {We aimed to explore perceptions of digital technology and the usage of information and communication technology (ICT) devices among patients with amyotrophic lateral sclerosis (ALS) and their caregivers. In October 2023, we held a nationwide webinar titled "ALS Café" and distributed a self-report questionnaire to patients with ALS and caregivers, including family members, which covered topics such as awareness, usage of accessibility features, and current support for the use of ICT devices. Thirty-one patients with ALS and 24 of their caregivers responded (average age: 57.1 ± 10.1). The ALS Functional Rating Scale-Revised (ALSFRS-R) score was 26.6 ± 14.1. Overall, 69.6 % of respondents were aware of accessibility features, 71.4 % of those under 70, and 50.0 % of those over 70. Frequently used features included browsing assistance (32.1 %), voice operation (30.4 %), mouse or touch pen operation (26.8 %), synthesized voice reading (23.2 %), gaze input operation (19.6 %), and switch operation (14.3 %). Self-help assistance for ICT devices was used by 65.8 % of respondents with an ALSFRS-R score ≥ 20 and 11.8 % with an ALSFRS-R score < 20. Regarding government services, 85 % of respondents were unaware of ICT support centers for persons with disabilities. This study revealed the awareness and usage of accessibility features of ICT devices among patients with ALS and their caregivers. Raising awareness of accessibility features among older adults and improving support systems for those with mild symptoms are necessary.}, } @article {pmid40614501, year = {2025}, author = {Yu, H and Wang, C and Phuntsho, S and He, T and Naidu, G and Han, DS and Shon, HK}, title = {Highly selective lithium recovery from seawater desalination brine using Li2TiO3 membrane-coated capacitive deionization.}, journal = {Water research}, volume = {285}, number = {}, pages = {124113}, doi = {10.1016/j.watres.2025.124113}, pmid = {40614501}, issn = {1879-2448}, abstract = {Selective lithium (Li) recovery from seawater-based resources is challenged by low Li concentrations and the presence of competing ions such as Na[+], K[+], Mg[2+], and Ca[2+]. This study presents an innovative approach by integrating capacitive deionization (CDI) with a titanium-based lithium-ion sieve (LIS) membrane-coated cathode and an anion exchange membrane (AEM)-coated anode for enhanced Li recovery from seawater desalination brine (SWDB). The cathode was fabricated using Li2TiO3 (LTO) adsorbent through rolling pressing and dip coating methods. Characterization confirmed the successful fabrication of the LTO membrane-coated electrode. The performance of the LTO-AEM-CDI system was evaluated using simulated SWDB through an adsorption-rinsing-desorption operational mode. The results indicated that the rinsing stage plays a crucial role in significantly enhancing Li selectivity. A 10-cycle stability test demonstrated the system's reliability, maintaining the active Li selectivity (ALS) consistently above 100 across all cycles. This research highlights the potential of combining LIS, membrane technologies, and CDI for effective Li extraction from seawater-based resources.}, } @article {pmid40614474, year = {2025}, author = {Montenegro, MF and Morales, JMN and Morán Vieyra, FE and Borsarelli, CD}, title = {Eco-friendly synthesis of a silver nanohybrid with carbon dots derived from Quebracho Colorado leaves and its application in the colorimetric detection of Al[3].}, journal = {Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy}, volume = {343}, number = {}, pages = {126628}, doi = {10.1016/j.saa.2025.126628}, pmid = {40614474}, issn = {1873-3557}, abstract = {The Schinopsis lorentzii tree leaves were utilized for the first time in the production of carbon dots (CDs) with a diameter of 6 nm through hydrothermal carbonization at 200 °C. The heating of AgNO3 aqueous solutions up to 70 °C in the presence of CDs results in the formation of silver nanohybrids (AgNP@CDs), with a zeta potential of -48 mV, a diameter of 33 nm, and a surface plasmon resonance (SPR) absorption band centered at 440 nm. Among the various cations examined, only the incorporation of Al[3+] in the AgNP@CDs solution induced a color shift from yellow to brown, leading to the formation of colloidal aggregates with an approximate diameter of 550 nm. The formation of AgNP@CDs nanohybrids and aggregates in the absence and presence of Al[3+], respectively, was modeled by combining UV-vis absorption spectra with multivariate curve resolution-alternating least squares (MCR-ALS) analysis. For the AgNP@CDs, a sequential nucleation-aggregation mechanism was observed, with a global activation energy of 28 kJ/mol. In the presence of Al[3+], a four-species sequential mechanism describes the progressive formation of larger aggregates, with dose-response curves that are characteristic of highly cooperative binding equilibriums with an average global binding constant of 7 × 10[4] M[-1]. The analytical performance of the AgNP@CDs resulted in a sensitivity of 0.03 μM, a linear range between 10 and 20 μM, and a limit of detection of 3.5 μM. These parameters are consistent with those previously reported for the colorimetric determination of Al[3+] using AgNPs capped with different molecules.}, } @article {pmid40613930, year = {2025}, author = {Qi, Y and Xu, J and Wang, Y and Gao, Y and Sun, Z and Deng, Z and Shao, Y and Li, P and Nieland, JDV}, title = {Changes of Sonic Hedgehog mediated FAK/ERK pathway proteins in amyotrophic lateral sclerosis model mice.}, journal = {Psychopharmacology}, volume = {}, number = {}, pages = {}, pmid = {40613930}, issn = {1432-2072}, support = {202303021221206//Shanxi Provincial Key Research and Development Project/ ; 2024-148//Shanxi Provincial Education Department/ ; 2024ZYY2B050//Health Commission of Shanxi Province/ ; }, } @article {pmid40613809, year = {2025}, author = {Veenstra, J and Ozog, D and Ghosh, S}, title = {Response to Yang et al's "A Disproportionality Analysis on Benzoyl Peroxide and Its Risk of Malignancy Using the FDA Adverse Event Reporting System".}, journal = {The Journal of investigative dermatology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jid.2025.05.025}, pmid = {40613809}, issn = {1523-1747}, } @article {pmid40612333, year = {2025}, author = {Rossip, MG and Hastings, J and Burwinkel, H and Lavrova, E and Steinbrenner, R and Bensaid, N and Cooke, DL and Pantanelli, SM}, title = {Relative Behavior of Modern Intraocular Lens Power Calculation Formulas Across a Realistic Range of Biometry Values.}, journal = {Clinical ophthalmology (Auckland, N.Z.)}, volume = {19}, number = {}, pages = {2037-2045}, pmid = {40612333}, issn = {1177-5467}, abstract = {PURPOSE: To investigate the relative performance of modern intraocular lens (IOL) power calculation formulas over a wide range of biometric parameters.

PATIENTS AND METHODS: Through the concept of emmetropization there exists a mean keratometry, anterior chamber depth, lens thickness, and white-to-white for a given axial length (AL). Using a database of biometric values from 2721 surgery naïve eyes, these relationships were modeled and used to create an artificial dataset of 170 eyes with an anatomically realistic distribution of biometric parameters. Biometric values for each artificial eye were entered into the ESCRS IOL power calculation website. The emmetropic IOL power was calculated for Barrett Universal II, Cooke K6, Kane, PEARL-DGS, HofferQST, EVO v2.0, and Hill-RBF v3.0. Separately, emmetropic IOL powers were calculated for the Zeiss AI formula. The disparity between the formulas was evaluated to determine the ALs at which they diverged.

RESULTS: For eyes with ALs between 22.5 and 28.1 mm, emmetropic IOL powers and spherical equivalent predictions differed by less than 0.25 D. Outside this range, spherical equivalent predictions differed by 0.25 D or more. At ALs < 19.5 mm the difference in emmetropic IOL power across the formulas exceeded 1.0 D.

CONCLUSION: This work helped to identify an implementation error in Pearl-DGS, which was corrected in collaboration with the formula's author. Cataract surgeons should consider that formula choice still has a clinically meaningful impact on refractive outcomes in eyes with axial lengths of <22.5 mm and >28.1 mm. We estimate that this may represent more than 10% of the population.}, } @article {pmid40612293, year = {2025}, author = {Bayleyegn Derso, T and Mengistu, BA and Demessie, Y and Fenta, MD and Getnet, K}, title = {Neural stem cells in adult neurogenesis and their therapeutic applications in neurodegenerative disorders: a concise review.}, journal = {Frontiers in molecular medicine}, volume = {5}, number = {}, pages = {1569717}, pmid = {40612293}, issn = {2674-0095}, abstract = {The idea of using stem cell therapy to treat neurodegenerative diseases has undergone significant change over the years and has made significant progress recently. Neurotrophins, growth factors, and transcription factors regulate neural stem cell proliferation and differentiation. Disruption of these regulatory mechanisms, including negative feedback, can contribute to neurodegenerative diseases. Contemporary research highlights a growing global concern regarding diverse neurodegenerative disorders affecting both humans and animals. These conditions arise from neuronal cell death, axonal regeneration failure, and impairment of neuronal structure. Current pharmacological treatments primarily offer symptomatic relief without altering disease progression. Consequently, researchers are investigating innovative therapeutic strategies, with neural stem cell therapy emerging as a promising avenue. Adult neural stem cells, embryonic neural stem cells, and induced pluripotent stem cells represent potential cell sources, although challenges such as ethical considerations and technical limitations remain. The therapeutic application of neural stem cells holds significant promise for addressing neurodegenerative diseases, including Alzheimer's disease, stroke, amyotrophic lateral sclerosis, spinal cord injury, and multiple sclerosis. Neural stem cell therapy aims to replenish lost neurons and promote neural regeneration in these conditions. While clinical trials have demonstrated some success in improving cognitive and motor functions in individuals with neurodegenerative impairments, challenges such as immunological rejection, the identification of compatible cell sources, ethical concerns, treatment efficacy, and potential side effects necessitate thorough investigation before widespread clinical implementation. Despite these challenges, neural stem cell-based therapy offers substantial potential for revolutionizing the treatment of neurodegenerative diseases and central nervous system injuries. This paper, therefore, explores adult neurogenesis and the therapeutic potential of neural stem cells within the dynamic field of neurodegenerative disorders.}, } @article {pmid40611592, year = {2025}, author = {DuVal, MG and Noga, T and Beecher, G}, title = {Long-Term Tofersen and CSF Macrophage Inclusions in Superoxide Dismutase 1 Amyotrophic Lateral Sclerosis.}, journal = {The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques}, volume = {}, number = {}, pages = {1-3}, doi = {10.1017/cjn.2025.10351}, pmid = {40611592}, issn = {0317-1671}, } @article {pmid40610342, year = {2025}, author = {Trubshaw, M and Yoganathan, K and Gohil, C and Stagg, CJ and Nobre, AC and Talbot, K and Woolrich, M and Thompson, AG and Turner, MR}, title = {Gamma activation spread reflects disease activity in amyotrophic lateral sclerosis.}, journal = {Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology}, volume = {}, number = {}, pages = {2110823}, doi = {10.1016/j.clinph.2025.2110823}, pmid = {40610342}, issn = {1872-8952}, abstract = {OBJECTIVE: A non-invasive measure of cerebral motor system dysfunction would be valuable as a biomarker in amyotrophic lateral sclerosis (ALS). Task-based magnetoencephalography (tMEG) measures the magnetic fields generated by cortical neuronal oscillatory activity during task performance. Gamma activations are periods of high-power and high-frequency cortical oscillations integral to motor control.

METHODS: tMEG was undertaken during 60 bilateral isometric hand grip exercises in ALS (n = 42) and compared with healthy controls (HC, n = 33). Gamma activation spread (GAS) was estimated by calculating the number of activated regions during each 100 ms time-bin and compared statistically between groups. Gamma activation patterns were visualised by plotting each participant's brain activity separately as a 2-dimensional video.

RESULTS: There was no difference in grip strength between groups. GAS was greatly increased in the ALS group compared to HC (p < 0.001) and correlated positively with rate of ALSFRS-R progression (t = 1.35, p = 0.023) and a fine motor sub-score (t = -1.18, p = 0.047).

CONCLUSIONS: ALS was associated with a marked increase in regional spread of gamma frequency activation, greater in those with higher disease progression rates.

SIGNIFICANCE: The regional spread of gamma activity may reflect disease activity in ALS, with potential application as an experimental medicine readout.}, } @article {pmid40610146, year = {2025}, author = {Olivieri, AC}, title = {Hazards of using multivariate curve resolution for processing first-order spectral data. A rotational ambiguity analysis.}, journal = {Analytica chimica acta}, volume = {1367}, number = {}, pages = {344304}, doi = {10.1016/j.aca.2025.344304}, pmid = {40610146}, issn = {1873-4324}, abstract = {BACKGROUND: A growing number of reports are discussing the use of multivariate curve resolution - alternating least-squares (MCR-ALS) to process matrices built with first-order data, e.g., spectra. Although the results are promising, almost no complementary analysis of the impact of rotational ambiguity on the obtained solutions has been reported.

RESULTS: Several experimental data sets involving spectra (near infrared, UV-visible absorption, fluorescence emission) were processed with MCR-ALS, and then analyzed with channel-wise N-BANDS regarding the presence of rotational ambiguity. In cases of low spectral overlapping, almost unique profiles were found in the retrieved analyte concentration profiles. In cases of high spectral overlapping, however, substantial ambiguity was estimated in the analyte concentration profiles, making the analytical results less reliable. This is even more pronounced when uncalibrated components occur in the test samples. Channel-wise N-BANDS calculations agreed with the results from randomly initialized MCR-ALS models.

SIGNIFICANCE: Researchers using MCR-ALS in multivariate calibration protocols based on first-order data should always accompany the decomposition results with a rotational ambiguity analysis. This would provide insight into the reliability of the retrieved profiles, the estimation of the analyte concentrations and the qualitative interpretation of the spectra.}, } @article {pmid40610071, year = {2025}, author = {Selvaraj, C and Vijayalakshmi, P and Desai, D and Manoharan, J}, title = {Proteostasis imbalance: Unraveling protein aggregation in neurodegenerative diseases and emerging therapeutic strategies.}, journal = {Advances in protein chemistry and structural biology}, volume = {146}, number = {}, pages = {1-34}, doi = {10.1016/bs.apcsb.2024.11.008}, pmid = {40610071}, issn = {1876-1631}, mesh = {Humans ; *Proteostasis ; *Neurodegenerative Diseases/metabolism/therapy/pathology ; Animals ; Autophagy ; *Protein Aggregation, Pathological/metabolism/therapy/pathology ; *Protein Aggregates ; }, abstract = {Neurodegenerative diseases such as Alzheimer's, Parkinson's, Huntington's, and ALS are defined by the accumulation of misfolded and aggregated proteins, which impair cellular function and result in progressive neuronal death. This chapter examines the critical function of proteostasis-cellular protein homeostasis-in sustaining neuronal health and its disruption as a key factor in disease progression. Proteostasis is upheld by a complex array of mechanisms, which encompass molecular chaperones, the ubiquitin-proteasome system, autophagy-lysosomal pathways, and mitochondrial quality control. Impairment of these systems leads to protein misfolding and aggregation, resulting in toxic cellular environments that promote neurodegeneration. Novel therapeutic approaches focus on restoring proteostasis through the enhancement of cellular protein folding, degradation, and clearance mechanisms. This encompasses small molecule chaperones, gene therapy, RNA-based treatments, immunotherapy, autophagy inducers, and stem cell-based approaches, each addressing distinct components of the proteostasis network to mitigate or prevent disease progression. While these therapies show potential, challenges persist, such as possible side effects, selective targeting, and the efficacy of blood-brain barrier penetration. Personalized medicine and combination therapies customized to specific disease profiles are increasingly recognized for their potential to improve efficacy and safety. This chapter consolidates recent developments in therapies aimed at proteostasis, addresses the challenges encountered in clinical applications, and outlines potential future directions for transformative treatments. Ongoing research indicates that proteostasis modulation may significantly alter the course of neurodegenerative disease treatment, potentially enhancing patient outcomes and quality of life.}, } @article {pmid40609634, year = {2025}, author = {Lukianenko, N and Kang, DM and Bekci, A and Kim, YK and Lim, S}, title = {Nucleocytoplasmic HDAC Inhibition Drives Acetylation-dependent TDP-43 Mislocalization and Disulfide-linked Oligomerization.}, journal = {Journal of molecular biology}, volume = {437}, number = {19}, pages = {169318}, doi = {10.1016/j.jmb.2025.169318}, pmid = {40609634}, issn = {1089-8638}, abstract = {TDP-43 proteinopathies, including amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD), are characterized by aberrant cytoplasmic mislocalization and aggregation of TDP-43. Here, we established a live-cell TDP43-BiFC model to visualize TDP-43 oligomerization in real time and screened diverse cellular stressors. Histone deacetylase (HDAC) inhibition emerged as the most potent trigger of TDP-43 oligomerization. In particular, selective inhibition of the shuttling HDAC4/5 with LMK-235 induced an early and robust formation of cytoplasmic TDP-43 oligomers, comparable to or even exceeding the effect of the pan-HDAC inhibitor apicidin. In contrast, nuclear-restricted HDAC1/3 inhibition by MS-275 prolonged TDP-43 retention in the nucleus with minimal cytoplasmic mislocalization or oligomerization, underscoring distinct roles for nuclear versus nucleocytoplasmic HDACs. Inhibition of cytoplasmic HDAC6 (tubastatin A) had no significant effect. Notably, both shuttling and pan-HDAC inhibition increased TDP-43 acetylation and promoted the accumulation of stable, disulfide-linked TDP-43 oligomers. These findings identify lysine acetylation as a key regulator of disulfide bond-dependent TDP-43 oligomerization and suggest that targeting nucleocytoplasmic HDACs could be a novel therapeutic strategy in TDP-43 proteinopathies.}, } @article {pmid40609398, year = {2025}, author = {Yazdanian, T and Azimi, P and Babu, S}, title = {Cervical spinal cord MRI in ALS individuals: a systematic review and meta-analysis.}, journal = {NeuroImage. Clinical}, volume = {47}, number = {}, pages = {103832}, pmid = {40609398}, issn = {2213-1582}, abstract = {BACKGROUND: Disease tracking and prognostication of amyotrophic lateral sclerosis (ALS) can be quite challenging in people living with ALS, due to the complexity of central nervous system disease biology. This systematic review and meta-analysis aim to summarize cervical spinal cord quantitative MRI (qMRI) biomarker changes in individuals with ALS.

METHODS: PubMed, Scopus, Cochrane Library, and Web of Science databases were searched up to August 2023. The terms used were "ALS", "cervical spinal cord", "MRI"," diffusion tensor imaging (DTI)", " fractional anisotropy (FA)", " mean diffusivity (MD) "," magnetization transfer ratio (MTR)", " cross-sectional area (CSA)", " radial diffusivity (RD) ", and " atrophy ". The Newcastle-Ottawa scale (NOS) was used to assess study quality. We calculated the pooled: 1) Standardized mean difference (SMD) and 95% CIs for comparative assessment of qMRI parameters in ALS individuals and the healthy population. 2) Estimate the mean of qMRI parameters for normative values in two groups by CMA software. Heterogeneity and publication bias were determined by the I-squared statistic and funnel plots.

RESULTS: Thirty studies, with 1817 participants (35.9 % female) were included in this review, and 29 had a NOS ≥ 5 which indicates high-quality of data overall. The SMD analysis showed (a) significant decrease in CSA along the whole length of cervical cord (C1-C7) (p value < 0.0001), with a preferential thinning of the cervical enlargement region (C4-C6 region) (p value < 0.0001) (b) significant decrease in FA (p value < 0.0001), particularly FA left lateral corticospinal tract (p value < 0.0001) and (c) a significant increase in MD (p value < 0.0001) in ALS individuals compared to controls. The pooled analysis reveals that the mean (SD) values for ALS individuals versus controls for (a) CSA (in mm[2]) were C1 [73.4 (0.75), 78.5 (0.67), 6.9 % difference]; C2 [70.6 (3.1), 71.5 (3.5), 1.2 % difference]; C3 [69.8(1.5), 74.9 (1.9), 7.3 % difference]; C4 [71.9 (1.8), 77.6 (2.8), 7.9 % difference]; C5 [71.8 (2.5), 79.5 (3.3), 10.7 % difference]; C6 [66.8 (2.7), 73.7 (3.7), 10.3 % difference]; C7 [56.7 (F2.2), 62.1 (2.5), 9.5 % difference]; (b) FA [0.54 (0.03), 0.56 (0.03)]; (c) MD[1.11 (0.18), 0.88(0)]; and (d) FA LLCST [ 0.65 (0.04), 0.77 (0.04)], respectively. The mean (SD) value of the MTR and RD for ALS individuals was 40.3 (2.3), and 0.70 (0.0).

CONCLUSIONS: qMRI metrics of spinal cord show discriminatory potential between ALS and healthy controls. The selective atrophy of the cervical enlargement (C4-C6) is replicable across multiple studies as seen in this metanalysis and hence is a potential imaging marker for quantifying and tracking lower motor neuron degeneration in ALS.}, } @article {pmid40608189, year = {2025}, author = {Sharma, VK}, title = {Dysbiosis and Neurodegeneration in ALS: Unraveling the Gut-Brain Axis.}, journal = {Neuromolecular medicine}, volume = {27}, number = {1}, pages = {50}, pmid = {40608189}, issn = {1559-1174}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/complications/physiopathology/microbiology/therapy ; *Dysbiosis/complications/physiopathology/therapy ; *Gastrointestinal Microbiome/physiology ; Animals ; *Brain-Gut Axis/physiology ; *Brain/physiopathology ; }, abstract = {Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease, is a neurodegenerative disorder marked by the progressive degeneration of motor neurons in the brain and spinal cord. Despite decades of research, ALS remains incurable, diagnostically elusive, and is accompanied by rapid clinical decline, morbidity, and mortality. Its pathophysiology involves a complex interplay of genetic mutations (SOD1, C9/f72), environmental triggers, oxidative stress, neuroinflammation, and the accumulation of misfolded proteins, such as TDP-43 and SOD1. These factors disrupt cellular homeostasis aggravates excitotoxicity and neuronal death. Existing treatments, such as riluzole (a glutamate release modulator) and edaravone (a free radical scavenger), offer limited benefits, modestly prolonging survival or slowing functional decline without halting progression. Investigational approaches include antisense oligonucleotides targeting mutant SOD1 or C9orf72 genes, stem cell-based motor neuron replacement, and biomarker discovery to enable earlier diagnosis and progression monitoring. ALS patients frequently exhibit gastrointestinal (GI) symptoms, including dysphagia, sialorrhea, constipation, delayed gastric emptying, and pancreatic/parotid deficiencies. These observations underscore a close association between GI dysfunction and ALS pathogenesis. Also, recent studies implicate the gut-brain-microbiota axis in disease evolution, with microbial metabolites influencing neuroimmune interactions, synaptic plasticity, myelination, and skeletal muscle function. These studies indicate that dysbiosis-an imbalance in gut microbiota-may have a crucial role in ALS progression by impairing intestinal barrier integrity, promoting endotoxemia, and driving systemic inflammation. Conversely, ALS progression itself worsens dysbiosis, creating a vicious cycle of neuroinflammation and neurodegeneration. Preclinical and clinical evidence suggests that interventions targeting gut microbiota-such as prebiotics, probiotics, antibiotics, or phage therapy-could alleviate symptoms and slow disease progression and specific probiotic strains have also shown promise in reducing oxidative stress and inflammation in animal models. These findings highlight the urgent need to elucidate the functional role of gut microbiota in ALS to unlock novel diagnostic and therapeutic avenues. This review synthesizes current knowledge on the pathophysiology of ALS, with a focus on the emerging role of the gut-brain-microbiota axis. It highlights how dysbiosis influences diverse disease markers and neurodegenerative mechanisms, offering insights into potential therapeutic strategies and identifying key research gaps and future directions.}, } @article {pmid40608121, year = {2025}, author = {Ruzi, Z and Zha, W and Yuan, HY and Liu, J}, title = {RNA G-quadruplexes: emerging regulators of gene expression and therapeutic targets.}, journal = {Functional & integrative genomics}, volume = {25}, number = {1}, pages = {143}, pmid = {40608121}, issn = {1438-7948}, support = {22262002//National Natural Science Foundation of China/ ; }, mesh = {*G-Quadruplexes ; Humans ; *Gene Expression Regulation ; *RNA/chemistry/genetics/metabolism ; Animals ; Neoplasms/genetics ; SARS-CoV-2 ; Neurodegenerative Diseases/genetics ; Alternative Splicing ; }, abstract = {RNA G-quadruplexes (rG4s) are non-canonical, four-stranded secondary structures formed by guanine-rich RNA sequences. These dynamic elements have garnered significant attention for their critical roles in regulating gene expression, including translation, alternative splicing, mRNA localization, and stability. This review synthesizes recent progress in understanding the structural determinants and formation dynamics of rG4s, highlighting the contributions of sequence motifs, ionic conditions, and RNA-binding proteins to their stability and function. Functional studies reveal that rG4s modulate key oncogenic transcripts (e.g., MYC, BCL2), contribute to splicing regulation, and influence intracellular RNA trafficking. In pathological contexts, rG4s have been implicated in the molecular etiology of cancers, neurodegenerative diseases such as amyotrophic lateral sclerosis and Fragile X syndrome, and viral replication mechanisms in pathogens including HIV and SARS-CoV-2. Advances in high-throughput techniques, such as G4-seq, rG4-seq, and live-cell imaging, have facilitated the global identification and characterization of rG4s in physiological and disease settings. Moreover, the therapeutic targeting of rG4s using small molecules holds promise for selective gene regulation and biomarker development. Comparative analyses across in vitro, in vivo, and clinical studies underscore the cell-type-specific and context-dependent roles of rG4s, especially in mediating stress responses and apoptosis. Despite methodological limitations and challenges in achieving targeted delivery, rG4s represent a compelling frontier for precision medicine. This review outlines current insights and future directions toward harnessing rG4 biology for therapeutic innovation.}, } @article {pmid40607987, year = {2025}, author = {Collins, M and Kwapiszeski, H and An, J and Garcia, D and Peller, D and Ladha, S and Bowser, R and Bakkar, N}, title = {Transthyretin abnormalities in amyotrophic lateral sclerosis: High molecular weight species in cerebrospinal fluid and stromal deposits in choroid plexus.}, journal = {Journal of neuropathology and experimental neurology}, volume = {}, number = {}, pages = {}, doi = {10.1093/jnen/nlaf076}, pmid = {40607987}, issn = {1554-6578}, support = {//Barrow Neurological Foundation/ ; F31 NS080614/NH/NIH HHS/United States ; }, abstract = {Transthyretin (TTR) is a plasma and cerebrospinal fluid (CSF) protein involved in transporting thyroid hormone and retinol, with additional roles in the central nervous system (CNS). The tetrameric structure of TTR is essential for its functions and tetramer dissociation and aggregation into pathological amyloid fibrils is implicated in multiple diseases. Altered levels of TTR have previously been described in amyotrophic lateral sclerosis (ALS) in both CSF and CNS tissue. However, whether altered TTR levels in ALS reflect TTR pathology in CSF or in the choroid plexus (CP) cells that synthesize CNS TTR is unknown. Here, we comprehensively assayed native and aggregated TTR in ALS patient CSF and postmortem ALS CP. Using a nondenaturing native polyacrylamide gel electrophoresis-based assay, we identified high molecular weight TTR aggregates in the CSF of ALS patients. We also observed increased levels of TTR RNA and protein in ALS CP, as well as TTR granule deposits in CP stroma of ALS but not control cases. Taken together, our results reveal new forms of TTR dysfunction in ALS and uncover TTR-related morphological abnormalities in the CP in ALS patients.}, } @article {pmid40607881, year = {2025}, author = {Song, X and Wang, X and Hu, F and Liu, P and Liu, Z and Yi, J and Xu, R and Cao, W and Zhang, Y and Wang, J and Grecucci, A and Yi, X and Chen, BT}, title = {Association of Reduced Brain Metabolism With Motor Function and Survival in Amyotrophic Lateral Sclerosis Patients With Neurofilament Heavy (NEFH) Gene Mutation.}, journal = {European journal of neurology}, volume = {32}, number = {7}, pages = {e70261}, pmid = {40607881}, issn = {1468-1331}, support = {2021YFA0805202//National Key Research and Development Program of China/ ; 2020XJ88//Scientific research project of Xiangnan University/ ; 2024ZZTS0954//Fundamental Research Funds for Central Universities of the Central South University/ ; 2023JJ50382//Natural Science Foundation of Hunan Province/ ; D202303077714//Scientific research project of Hunan Provincial Health Commission/ ; //"The 14th Five-Year Plan" Application Characteristic Discipline of Hunan Province/ ; //the Aid Program for Science and Technology Innovative Research Team in Higher Educational Institutions of Hunan Province, China/ ; 2021ZD0201803//Science and Technology Innovation 2030/ ; 82171431//Program of the National Natural Science Foundation of China/ ; 82371445//Program of the National Natural Science Foundation of China/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/metabolism/mortality/diagnostic imaging ; Female ; Male ; Middle Aged ; *Neurofilament Proteins/genetics ; Mutation ; *Brain/metabolism/diagnostic imaging ; Aged ; Prospective Studies ; Adult ; Positron Emission Tomography Computed Tomography ; Fluorodeoxyglucose F18 ; Glucose/metabolism ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that impairs both upper and lower motor neurons. Mutations in the neurofilament heavy (NEFH) gene are associated with a higher risk for ALS. This study aimed to evaluate the brain metabolism in patients with ALS and NEFH gene mutations (NEFH-ALS) and assess its correlation with emotional and cognitive changes.

METHODS: This prospective study enrolled 119 patients with ALS and 128 age- and gender-matched health controls. Study assessments included demographic data collection, questionnaires for motor function, cognition, and depression, and brain F-18 FDG PET/CT (18F-fluorodeoxyglucose positron emission tomography (PET)/computed tomography (CT)) scan. Correlation between brain metabolism and clinical questionnaire scores was performed. Chain-mediation model analysis for the NEFH-ALS group was conducted. Cox regression and Kaplan-Meier survival analysis were also performed.

RESULTS: There were 26 NEFH-ALS patients. Patients with NEFH-ALS showed brain glucose hypometabolism in the cortex-striatum/limbic system-brainstem circuit when compared with healthy controls (p < 0.05). Decreased brain glucose metabolism was correlated with impairments of motor function (r = 0.477, p = 0.014, FDR corrected p = 0.014), cognitive scores (r = 0.549, p = 0.004, FDR corrected p = 0.009), and depression (r = -0.523, p = 0.009, FDR corrected p = 0.009). This study showed that brain glucose hypometabolism could lead to impairment of motor function, which was mediated by cognition and depression. Survival analysis showed that brain glucose metabolism was an independent prognostic factor for patients with ALS.

CONCLUSIONS: Reduced brain glucose metabolism in the cortex-striatum/limbic system-brainstem circuit may potentially serve as an independent prognostic factor for patients with ALS and NEFH mutation.}, } @article {pmid40607624, year = {2025}, author = {Holdom, CJ and Williamson, JL and O'Reilly, G and Henderson, RD and Neville, S and Ngo, ST and Dick, TJM and Steyn, FJ}, title = {Lower-limb biomechanics in motor neuron disease: a joint-level perspective of gait disruption.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {}, number = {}, pages = {1-11}, doi = {10.1080/21678421.2025.2523945}, pmid = {40607624}, issn = {2167-9223}, abstract = {Background: Motor neuron disease (MND) profoundly impacts mobility, yet gait-specific dysfunctions due to MND remain poorly understood. Methods: We characterized lower-limb gait alterations in people living with MND (plwMND) using advanced biomechanical tools. Nine plwMND and nine non-neurodegenerative disease controls walked on an instrumented treadmill at self-selected speeds. Ground reaction forces and joint motions were measured to model lower-limb kinetics, kinematics, and energetics. Results: PlwMND had reduced forward propulsive (p < 0.001) and braking (p = 0.002) ground reaction forces. Ankle range of motion was 10.0 ± 3.1° lower (p = 0.035) with peak positive ankle moment and power 33% and 72% lower, respectively (both: p < 0.001), in plwMND compared to controls. Conclusions: These lower-limb impairments highlight the ankle as an early and critical locus of dysfunction, with distal weakness driving compensatory proximal strategies, increasing walking inefficiency and fatigue. Integrating biomechanical and clinical data offers new insights into gait disruption in MND, supporting the development of targeted, personalized interventions to maintain independent mobility.}, } @article {pmid40607043, year = {2025}, author = {Doeleman, LC and de Jong, JFF and van Eeden, VGM and Schober, P and Hollmann, MW and van Schuppen, H}, title = {Airway management by ambulance nurses during out-of-hospital cardiac arrest.}, journal = {Resuscitation plus}, volume = {25}, number = {}, pages = {100999}, pmid = {40607043}, issn = {2666-5204}, abstract = {BACKGROUND: Adequate airway management in out-of-hospital cardiac arrest (OHCA) is crucial for ventilation and oxygenation. Advanced airway management with a supraglottic airway device (SAD) or endotracheal tube (ETT) follows bag-valve-mask (BVM) ventilation, with emergency front-of-neck access as a rescue-option. EMS protocols on airway management in OHCA have changed over the years and during the COVID-pandemic. This study assessed subsequent changes in airway management and the success of different strategies.

METHODS: An observational study was conducted with data from ARREST, 2019-2023. All consecutive adult OHCA patients who had resuscitation attempted by EMS were included. Patients were excluded if helicopter emergency medical services were involved. Changes in devices used intra-arrest and their first-pass success were analyzed.

RESULTS: The proportion of cases with an SAD attempt increased, and with an ETT decreased. The definitive airway device used was an SAD in 59% (95% CI: 57-60%), an ETT in 21% (95% CI: 19-22%), and BVM in 14% (95% CI: 13-15%). First pass success for ETT increased from 53% to 68%. Average SAD first pass success was 93%.

CONCLUSION: During cardiopulmonary resuscitation (CPR) by ambulance nurses, the use of SADs increased, and that of ETTs decreased. Although ETT first pass success improved, it was lower than the guideline-recommended standard for performing intubations prehospitally. First pass success for SAD was high. This adds support for current Dutch ambulance guidelines recommending an SAD for primary choice of advanced airway by EMS during CPR. However, improvement of intubation techniques and skills remain a necessity for selected OHCA patients.}, } @article {pmid40606671, year = {2025}, author = {Zhan, X and Xuan, T and Chen, X and He, J and Ren, Y and Meng, Y and Chen, G and Li, H}, title = {Case Report: A case of ALS type 6 associated with a FUS gene variant and right limb muscle weakness and atrophy as the initial symptom.}, journal = {Frontiers in genetics}, volume = {16}, number = {}, pages = {1578249}, pmid = {40606671}, issn = {1664-8021}, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive degeneration of upper and lower motor neurons. This degeneration results in increasing muscle weakness, ultimately culminating in respiratory failure and death. Mutations in the fused in sarcoma (FUS) gene have been identified as a significant cause of ALS. Here, we present the case of a 40-year-old woman who exhibited right limb muscle weakness and atrophy as her initial symptom. Whole genome sequencing revealed a mutation in the FUS gene, specifically c.1450_1456delinsCCC (p.Tyr484Profs*44), leading to a diagnosis of ALS type 6 (ALS6). The c.1450_1456delinsCCC (p.Tyr484Profs*44) mutation is a frameshift mutation resulting from a non-triplet base deletion in the coding region of the FUS gene. This mutation is novel and has not been previously reported in China or internationally. Furthermore, the onset of muscle weakness and atrophy exclusively in the ipsilateral limb is very rare among ALS patients, and we have found no related reports. This case report aims to enhance medical professionals' understanding of the complexities associated with ALS caused by FUS gene mutations and the onset of ALS symptoms, thereby facilitating more accurate clinical diagnosis and treatment.}, } @article {pmid40605998, year = {2025}, author = {Qin, H and Hussain, L and Liu, Z and Yan, X and Awwad, FA and Butt, FM and Salaria, UA and Ismail, EAA}, title = {Optimizing deep learning models to combat amyotrophic lateral sclerosis (ALS) disease progression.}, journal = {Digital health}, volume = {11}, number = {}, pages = {20552076251349719}, pmid = {40605998}, issn = {2055-2076}, abstract = {OBJECTIVE: Amyotrophic lateral sclerosis (ALS), a devastating neurodegenerative disease, poses a significant challenge for targeted treatment development. Accurate prediction of its progression is crucial for this endeavor.

METHODS: This study investigated deep learning methods for ALS progression prediction using the publicly available PRO-ACT dataset. Initially, machine learning models (XGBoost, LightGBM) and a deep learning sequential model were evaluated with default parameters, using R-squared (R2) and Root Mean Squared Error (RMSE) as performance metrics.

RESULTS: Notably, the deep learning model demonstrated superior predictive performance with default settings (RMSE: 4.565, R2: 0.716), followed by XGBoost (RMSE: 4.625, R2: 0.709) and LightGBM (RMSE: 4.596, R2: 0.716). Subsequently, hyperparameter optimization significantly enhanced the deep learning model's performance, achieving the highest prediction accuracy (RMSE: 4.511, R2: 0.718). Slight improvements were also observed for XGBoost (RMSE: 4.532, R2: 0.715) and LightGBM (RMSE: 4.551, R2: 0.716). Furthermore, the optimized XGBoost model demonstrated exceptional classification performance in distinguishing between bulbar and limb onset ALS, with a sensitivity of 100%, specificity of 97.44%, accuracy of 97.96%, F1-score of 95.96%, Matthews Correlation Coefficient (MCC) of 94.12%, and an Area Under the Curve (AUC) of 0.9550. Feature importance analysis with optimized XGBoost identified ZBTB2P1 as the most influential feature, followed by RNF181, with WASH9P being the least influential among the top eight.

CONCLUSIONS: These findings convincingly demonstrate the potential of optimized XGBoost and deep learning for ALS progression prediction and classification, particularly with optimized parameters. This approach offers significant potential for early risk stratification, personalized treatment planning, enhanced prognostic communication, diagnostic support, streamlined disease monitoring, and improved clinical decision-making, ultimately contributing to better patient outcomes and potentially reducing ALS-related mortality.}, } @article {pmid40605510, year = {2025}, author = {Yeh, TS and Rotem, RS and Weisskopf, MG}, title = {Type 2 diabetes mellitus, antidiabetics, and the risk of amyotrophic lateral sclerosis.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {}, number = {}, pages = {1-9}, pmid = {40605510}, issn = {2167-9223}, support = {P30 ES000002/ES/NIEHS NIH HHS/United States ; R21 NS099910/NS/NINDS NIH HHS/United States ; }, abstract = {Background: Research on the link between Type 2 Diabetes mellitus (T2DM) and amyotrophic lateral sclerosis (ALS) has produced mixed results. The potential role of antidiabetic medications in ALS etiology is also unclear. To contribute to these discussions, we aimed to examine the connections between T2DM, antidiabetic medications, and ALS using data from a large Israeli health fund. Methods: A total of 504 ALS cases diagnosed in 2002-2018 and 42,873 matched controls were considered in this population-based nested case-control study. T2DM was ascertained using diagnosis codes, laboratory test results, and medication use history, employing a 3-year lag from initial ALS diagnosis date to minimize chances for reverse causation. Multivariable-adjusted odds ratios (OR) were estimated for the association between T2DM, antidiabetic medications, and ALS. Results: T2DM overall was not linked with ALS (multivariable-adjusted odds ratio (OR) = 0.94, 95% confidence interval (CI): 0.72-1.23). However, T2DM with a history of insulin use showed a protective association with ALS (OR = 0.29; 95% CI = 0.09-0.92) compared to the non-T2DM group. A similar trend of protective associations with ALS was observed for T2DM with history of use of other antidiabetic medications, but none were statistically significant, and all associations were further attenuated after adjusting for insulin use. Conclusions: We observe a potential protective effect of T2DM-linked insulin use on risk of ALS. Although caution is necessary due to the limited number of ALS cases with insulin exposure, the observed protective association may suggest a biological pathway worth exploring for future therapeutic development.}, } @article {pmid40605360, year = {2025}, author = {De Wel, B and Mobach, T and Pfeffer, G and Jewett, G}, title = {Tofersen Treatment Normalizes Neurofilament Levels in Autosomal Recessive SOD1 Amyotrophic Lateral Sclerosis.}, journal = {The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques}, volume = {}, number = {}, pages = {1-2}, doi = {10.1017/cjn.2025.10350}, pmid = {40605360}, issn = {0317-1671}, } @article {pmid40603051, year = {2025}, author = {Ito, L and Galipon, J}, title = {[Development of RNA Hydrogels as a Potential System for Intracellular Biomimicry: A Method for the In Vitro Synthesis of ALS/FTD-related (G4C2)n RNA with over 100 Repeats].}, journal = {Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan}, volume = {145}, number = {7}, pages = {601-607}, doi = {10.1248/yakushi.24-00209-3}, pmid = {40603051}, issn = {1347-5231}, mesh = {*Amyotrophic Lateral Sclerosis/genetics ; *RNA/chemical synthesis/genetics/chemistry ; Humans ; *Hydrogels ; G-Quadruplexes ; C9orf72 Protein/genetics ; DNA-Directed RNA Polymerases ; *Repetitive Sequences, Nucleic Acid/genetics ; Viral Proteins ; *Biomimetics/methods ; RNA-Binding Proteins/metabolism ; *Frontotemporal Dementia/genetics ; }, abstract = {In the motor neurons of amyotrophic lateral sclerosis (ALS) patients, excessive (G4C2)n repeats in the intronic region of the C9orf72 gene are transcribed to RNA, forming G-quadruplexes that sequester RNA-binding proteins, leading to gelation within the cytoplasm as one of the many mechanisms leading to pathogenesis. While ALS patients frequently harbor over 700 repeats, this kind of 100% GC-rich region is very difficult to clone, and past studies report the necessity to add additional sequences in the middle to clone more than a few dozen repeats. The goal of this study was the in vitro production of the longest repetitive RNA to date consisting solely of (G4C2)n repeats. T4 DNA ligase was used to connect (G4C2)10 stretches of DNA with 3nt overhangs. Then, using a heat-resistant T7 RNA polymerase, the RNA obtained contained transcripts over 100 repeats. Artificial biomimetic RNA gels generated by scaling up this synthesis method are expected to contribute to elucidating the molecular mechanisms of repetitive sequence-related pathogenesis, as well as screening for drugs that can disrupt the gel structure.}, } @article {pmid40603049, year = {2025}, author = {Tsuiji, H}, title = {[Elucidation of the Molecular Mechanism Underlying Aberrant Formation of RNA Granules in Neurons of ALS Patients and Its Regulation].}, journal = {Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan}, volume = {145}, number = {7}, pages = {583-588}, doi = {10.1248/yakushi.24-00209-1}, pmid = {40603049}, issn = {1347-5231}, mesh = {*Amyotrophic Lateral Sclerosis/genetics/pathology/metabolism/therapy/etiology ; Humans ; RNA-Binding Protein FUS/metabolism ; *DNA-Binding Proteins/metabolism/genetics ; C9orf72 Protein/genetics ; *RNA/metabolism/genetics ; *Motor Neurons/metabolism ; Animals ; RNA Splicing/genetics ; RNA-Binding Proteins/metabolism ; *Cytoplasmic Granules/metabolism ; Dipeptides/metabolism ; Protein Biosynthesis/genetics ; Spliceosomes/metabolism ; DNA Repeat Expansion/genetics ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disease characterized by progressive muscle atrophy throughout the body. In nearly all ALS patients, abnormal accumulation of the RNA-binding protein TDP-43 is observed in degenerating motor neurons. We have found that RNA-binding proteins such as TDP-43 and FUS are concentrated in GEM bodies, where they contribute to the integrity of the spliceosome machinery involved in pre-RNA splicing. Additionally, the most common cause of ALS, repeat expansion in the C9orf72 gene, triggers abnormal repeat-associated non-AUG (RAN) translation, leading to the accumulation of neurotoxic dipeptide repeat (DPR) proteins. We have identified that these DPR proteins may inhibit GEM body formation and contribute to ALS pathology. Furthermore, therapeutic approaches to suppress RAN translation using dCas13 technology are under development, offering promising new strategies to address abnormalities in RNA metabolism in ALS.}, } @article {pmid40602832, year = {2025}, author = {Abgueguen, E and Tortarolo, M and Rouviere, L and Marcuzzo, S and Camporeale, L and Henriques, A and Pasetto, L and Culley, GR and Bonetto, V and Marian, A and Lejeune, BL and Visbecq, A and Lauria, G and Kabashi, E and Callizot, N and Bendotti, C and Miniou, PY}, title = {Sephin1 reduces TDP-43 cytoplasmic mislocalization and improves motor neuron survival in ALS models.}, journal = {Life science alliance}, volume = {8}, number = {9}, pages = {}, pmid = {40602832}, issn = {2575-1077}, mesh = {Animals ; *Amyotrophic Lateral Sclerosis/metabolism/drug therapy/pathology ; *Motor Neurons/drug effects/metabolism ; *DNA-Binding Proteins/metabolism/genetics ; Disease Models, Animal ; Mice ; Zebrafish ; Humans ; Unfolded Protein Response/drug effects ; Mice, Transgenic ; Cell Survival/drug effects ; Endoplasmic Reticulum Stress/drug effects ; Cytoplasm/metabolism ; Mitochondria/metabolism/drug effects ; Reactive Oxygen Species/metabolism ; Apoptosis/drug effects ; Oxidative Stress/drug effects ; Spinal Cord/metabolism ; }, abstract = {A pathological hallmark of ALS is the abnormal accumulation of misfolded proteins (e.g., TDP-43) and enlarged endoplasmic reticulum (ER), indicating ER stress. To resolve this stress, cells initiate the Unfolded Protein Response (UPR). However, unresolved stress leads to apoptosis. In ALS, UPR activation fails to resolve proteostasis impairment. UPR activation modulators, among them Sephin1, reduce protein aggregates and improve motor neuron survival in ALS models. We demonstrate that following glutamate intoxication, Sephin1 increases motor neuron survival by reducing mitochondria ROS production and extranuclear TDP-43. Sephin1 reduces abnormal splicing because of TDP-43 nuclear loss of function following oxidative stress. In SOD1[G93A] mice, Sephin1 treatment decreases TDP-43 in triton-insoluble fraction, improving motor neuron survival in spinal cord. Sephin1 improves motor neurons survival, motor function and survival of mutated TDP-43 transgenic zebrafish. Sephin1 improves motor neuron survival in ALS models by reducing TDP-43 cytoplasmic mislocalization and its toxicity. These findings open new therapeutic opportunities for Sephin1 in neurodegenerative pathologies with TDP-43 proteinopathy, including ALS.}, } @article {pmid40602557, year = {2025}, author = {Rodriguez-Romano, A and Gonzalez-Valdivieso, J and Moreno-Martinez, L and Vázquez Costa, JF and Osta, R and Rico, P}, title = {Injectable borax-loaded alginate hydrogels reduce muscle atrophy, modulate inflammation, and promote neuroprotection in the SOD1[G93A] mouse model of ALS through mechanisms involving IGF-Akt-mTOR signaling.}, journal = {International journal of biological macromolecules}, volume = {319}, number = {Pt 4}, pages = {145645}, doi = {10.1016/j.ijbiomac.2025.145645}, pmid = {40602557}, issn = {1879-0003}, mesh = {Animals ; *Amyotrophic Lateral Sclerosis/drug therapy/metabolism/pathology/genetics ; *Hydrogels/chemistry ; Mice ; *Muscular Atrophy/drug therapy/pathology/metabolism ; Disease Models, Animal ; *Alginates/chemistry ; Signal Transduction/drug effects ; Proto-Oncogene Proteins c-akt/metabolism ; TOR Serine-Threonine Kinases/metabolism ; Superoxide Dismutase-1/genetics ; Inflammation/drug therapy/pathology ; Motor Neurons/drug effects/metabolism ; *Neuroprotection/drug effects ; Neuroprotective Agents/pharmacology ; Mice, Transgenic ; Muscle, Skeletal/drug effects/pathology/metabolism ; Borates ; }, abstract = {Amyotrophic Lateral Sclerosis (ALS) is a prevalent condition characterized by motor neuron loss and skeletal muscle paralysis. Despite being associated to mutations in over 40 genes, its etiology remains elusive without a cure or effective treatment. ALS, historically considered a motor neuron disease, is defined today as a multisystem disorder involving non-neuronal cell types, including early muscle pathology independent of motor neuron degeneration (dying back hypothesis), thus skeletal muscle actively contributes to disease pathology, making it a viable therapeutic target for ALS. Our previous research has shown that boron transporter NaBC1 (encoded by the SLC4A11 gene), after activation co-localizes with integrins and growth factor receptors synergistically enhancing muscle repair. Here we investigate the effects of injectable alginate-based hydrogels for controlled local borax release in Amyotrophic Lateral Sclerosis muscle. Treated mice showed improved motor function, prolonged survival, and activation of essential muscle metabolic pathways, leading to enhanced muscle repair and reduced atrophy and inflammation. Interestingly, local muscle repair activation provided retrograde neuroprotection by preserving motor neurons and reducing neuro-inflammation. This study highlights the role of muscle tissue in ALS pathology, supporting its targeting with NaBC1-based therapies for muscle regeneration.}, } @article {pmid40602529, year = {2025}, author = {Lai, IC and Wei, JC}, title = {Comment on Mendoza et al's "Association between use of antihypertensives and treatment of actinic keratoses: A TriNetX population-based study".}, journal = {Journal of the American Academy of Dermatology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jaad.2025.03.105}, pmid = {40602529}, issn = {1097-6787}, } @article {pmid40601808, year = {2025}, author = {Huang, J and Wang, B}, title = {Nanoscale Insights into the Formation Reaction Mechanism of Si-Al Oligomers in Alkali-Activated Materials.}, journal = {Langmuir : the ACS journal of surfaces and colloids}, volume = {41}, number = {27}, pages = {17415-17425}, doi = {10.1021/acs.langmuir.4c05076}, pmid = {40601808}, issn = {1520-5827}, abstract = {Alkali-activated materials (AAM) have garnered significant attention as environmentally friendly alternatives to cement due to their potential to mitigate greenhouse gas emissions and facilitate the effective utilization of industrial waste streams. Silicon-aluminum (Si-Al) monomers serve as the cornerstone units within the nanocomposite structure of AAMs, playing a pivotal role in the polycondensation reactions (PR) that govern their formation. Despite extensive research on the PR processes within AAM, the nanoscale reaction mechanisms remain elusive. In this study, MD simulations based on the ReaxFF were employed to delve into the structural evolution and reaction mechanisms of PR processes at the nanoscale. Analyses employing radial distribution functions, bond lengths, and bond angles demonstrated the robustness of the models developed in this investigation. The simulations revealed that when three Si-Al nanomolecular monomers, namely [SiO2(OH)2][2-], [SiO(OH)3][-], and [Al(OH)4][-], undergo pairwise PR, distinct reaction pathways emerge, leading to the formation of various Si-Al oligomers that collectively constitute the framework of the AAM gel. During the assembly of Si-Al oligomers, we aim to shed light on the crucial role played by Al monomers in driving the reaction forward and the subsequent polymerization of Si-Al oligomers. This disparity underscores Al's pivotal function in the PR mechanism, illuminating its indispensable role in governing the molecular architecture and kinetics of these complexes.}, } @article {pmid40600544, year = {2025}, author = {El Elhaj, A and Onger, ME}, title = {Exploring Neurodegenerative Diseases: Bridging the Gap between in vitro and in vivo Models.}, journal = {Current pharmaceutical design}, volume = {}, number = {}, pages = {}, doi = {10.2174/0113816128374254250605070049}, pmid = {40600544}, issn = {1873-4286}, abstract = {Neurological disorders are brain conditions characterized by the loss of nerve cells, leading to a decline in function. Standard examples include dementia, tremors, involuntary movements, muscle weakness, and autoimmune attacks. The most common form of dementia is Alzheimer's, affecting over 5 million elderly individuals, while tremors, stiffness, and slow movement are caused by Parkinson's. Involuntary movements and emotional problems are caused by Huntington's, while muscle weakness and eventual demise are caused by Amyotrophic lateral sclerosis. Vision problems, fatigue, and difficulty walking are caused by Multiple sclerosis (MS), an autoimmune disease that attacks the myelin sheath. In vitro models provide cost and complexity reduction, environmental control, and high-through". Researchers employ both cell-based (in vitro) and animal- based (in vivo) models to investigate neurodegenerative illnesses and endeavor to formulate novel treatments for diverse conditions. In vitro models provide cost and complexity reduction, environment control, and high-throughput screening of potential therapeutic agents compared to in vivo models. Nevertheless, they possess constraints, including the absence of intricate interactions that transpire in the entire organism and the inability to reproduce the disease progression completely.}, } @article {pmid40600271, year = {2025}, author = {Narayanan, A and Seaberg, BL and Buxton, A and Vernino, A and Williams, VE and Matarazzo, A and Kekre, J and Subramanian, B and Wang, W and Rutkowski, JM and Hook, M and McCreedy, DA and Muthuchamy, M and Rimer, M}, title = {Lymphatic dysfunction correlates with inflammation in a mouse model of amyotrophic lateral sclerosis.}, journal = {Disease models & mechanisms}, volume = {18}, number = {7}, pages = {}, pmid = {40600271}, issn = {1754-8411}, support = {W81XWH2210678//Congressionally Directed Medical Research Programs/ ; W81XWH2210678//U.S. Department of Defense/ ; //Texas A and M University/ ; 25POST1378441//American Heart Association/ ; }, mesh = {Animals ; *Amyotrophic Lateral Sclerosis/pathology/physiopathology/complications ; Disease Models, Animal ; *Inflammation/pathology/physiopathology/complications ; *Lymphatic Vessels/physiopathology/pathology ; Spinal Cord/pathology/physiopathology ; Muscle, Skeletal/pathology/physiopathology ; Mice ; Mice, Transgenic ; Superoxide Dismutase-1/metabolism ; Mice, Inbred C57BL ; *Lymphatic System/physiopathology/pathology ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a rapidly progressive, ultimately fatal neurodegenerative disease, without effective modifying treatments. It affects both lower and upper motor neurons, causing skeletal muscle denervation and paralysis. Regardless of the mechanisms that initiate and drive ALS, chronic neuroinflammation and systemic immune system activation play key roles in disease progression. The lymphatic system is a network of vessels and organs essential for immune surveillance, tissue fluid balance and lipid absorption, critical for the resolution and progression of inflammation in the periphery. Its recent rediscovery in the central nervous system raises the possibility of it playing similar roles in neurological and neurodegenerative diseases featuring prominent neuroinflammation, such as ALS. We hypothesized that the structure and function of lymphatics are compromised in the most widely used murine model of ALS, the SOD1-G93A mouse. We found that these mice exhibit lymph transport dysfunction, diminished intrinsic lymphatic vessel tonic and phasic contractions, and an association between inflammation and lymphatic marker upregulation, despite absence of major structural changes in lymphatic network coverage in key affected tissues in the disease, skeletal muscle and spinal cord.}, } @article {pmid40599765, year = {2025}, author = {Wei, X and Qin, W}, title = {Exploring causal links between brain functional networks and neurodegenerative disease risk using Mendelian randomization.}, journal = {Journal of Alzheimer's disease reports}, volume = {9}, number = {}, pages = {25424823251348844}, pmid = {40599765}, issn = {2542-4823}, abstract = {BACKGROUND: Resting-state functional magnetic resonance imaging (rsfMRI) is pivotal for mapping alterations in brain functional networks associated with neurodegenerative diseases, particularly Alzheimer's disease (AD). However, the causal mechanisms linking such network dysfunction to disease pathogenesis remain unresolved.

OBJECTIVE: This study aimed to elucidate bidirectional causal relationships between 191 resting-state fMRI phenotypes (derived from 34,691 individuals) and six neurodegenerative diseases, specifically AD, amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), multiple sclerosis (MS), dementia with Lewy bodies (DLB), and Parkinson's disease (PD), using disease-specific GWAS data from European-ancestry cohorts.

METHODS: Bidirectional two-sample Mendelian randomization (MR) was performed using rsfMRI phenotypes from Zhao et al. (2022) and GWAS summary statistics (AD: ieu-b-5067/ebi-a-GCST90027158, ALS: ebi-a-GCST90027164, FTD: ieu-b-43, MS: ieu-b-18, DLB: ebi-a-GCST90001390, PD: ieu-b-7). Instrumental variables were filtered for significance (p < 5 × 10^-8), with sensitivity analyses (MR-PRESSO, Cochran's Q, MR-Egger) to ensure robustness.

RESULTS: Forward MR identified 26 rsfMRI phenotypes causally linked to neurodegenerative diseases. AD risk was associated with reduced cerebellum-subcortical connectivity (OR = 0.957, p = 0.004), while heightened cerebellar activity increased DLB risk (OR = 2.58, p = 0.0063). Reverse MR revealed 64 disease-to-network effects: AD altered default mode network connectivity (OR = 0.965, p = 0.034), and PD disrupted salience-central executive network interactions (OR = 0.950, p = 0.00011).

CONCLUSIONS: This study establishes robust bidirectional causal pathways between brain functional networks and neurodegenerative diseases, with AD showing unique vulnerability in cerebellar-subcortical and default mode circuits. These findings highlight network-specific therapeutic targets for AD and related disorders.}, } @article {pmid40597943, year = {2025}, author = {Duan, Q and Li, C and Wei, C and Wang, Q and Wang, B and Sun, L and He, Y and Qin, J and Huang, X}, title = {Botulinum toxin type A for amyotrophic lateral sclerosis lower limb spasm: two case reports.}, journal = {BMC neurology}, volume = {25}, number = {1}, pages = {263}, pmid = {40597943}, issn = {1471-2377}, support = {No.2024AFD137//the Natural Science Foundation of Hubei Province (Joint Fund Program)/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/complications/drug therapy ; Male ; *Botulinum Toxins, Type A/therapeutic use/administration & dosage ; Middle Aged ; *Neuromuscular Agents/therapeutic use/administration & dosage ; *Lower Extremity/physiopathology ; *Muscle Spasticity/drug therapy/etiology ; *Spasm/drug therapy/etiology ; }, abstract = {BACKGROUND: Patients with amyotrophic lateral sclerosis (ALS) often experience spasticity, which can severely affect their ability to perform basic activities like standing and walking, potentially diminishing their already compromised quality of life. Botulinum toxin type A (BTX-A) is a first-line drug for spastic management. However, there are limited reports on its effectiveness in reducing muscle tone among ALS patients, with scarcely any related research conducted in China. We conducted the clinical observation and follow-up study through the relevant ethical post (ChiCTR2200061794). Clinical registration was on July 2, 2022. All participants provided written informed consent.

CASE PRESENTATION: We report two cases of middle-aged male patients, both diagnosed with ALS, who presented with symptoms such as limb stiffness and walking limitation due to increased muscle tone in the lower limbs. Based on the spasticity of the patient's lower limbs, the corresponding target muscles were selected for BTX-A treatment under ultrasound guidance, and the patients were evaluated on relevant functional scales before injection (baseline, T0) and at three follow-up visits (T1: 2 weeks, T2: 4 weeks, T3: 8 weeks).

CONCLUSION: Appropriate BTX-A injected into the target muscles could effectively depress the spasticity of ALS patients without apparent side effects.}, } @article {pmid40596818, year = {2025}, author = {Moreno-García, L and Moreno-Martínez, L and de la Torre, M and Macías-Redondo, S and García-Redondo, A and Osta, R and Toivonen, JM and Calvo, AC}, title = {Circular RNA expression in ALS is progressively deregulated and tissue-dependent.}, journal = {BMC genomics}, volume = {26}, number = {1}, pages = {576}, pmid = {40596818}, issn = {1471-2164}, mesh = {*Amyotrophic Lateral Sclerosis/genetics/pathology/metabolism ; *RNA, Circular/genetics/metabolism ; Animals ; Humans ; Mice ; Male ; Female ; Spinal Cord/metabolism ; Disease Models, Animal ; Muscle, Skeletal/metabolism ; Mice, Transgenic ; Superoxide Dismutase-1/genetics ; Organ Specificity ; *Gene Expression Regulation ; }, abstract = {BACKGROUND: There is increasing evidence on the role of circular RNAs (circRNAs) in neuronal and muscular processes. Accordingly, their dysregulation is associated with neurodegenerative diseases and myopathies. We investigated circRNA expression in the central nervous system (CNS) and skeletal muscle, the two main tissues affected in amyotrophic lateral sclerosis (ALS).

RESULTS: Based on circRNA sequencing analysis in spinal cord from ALS mice (SOD1G93A) followed by a literature search, 30 circRNAs potentially involved in ALS were tested. All selected circRNAs were downregulated in the SOD1G93A spinal cord, whereas only half of these were quantifiable and were generally upregulated in quadriceps muscle of SOD1G93A mice. Such tissue-dependent expression pattern was observed in both sexes and circRNA abundance in the spinal cord was higher than in the muscle, both in wild type and in SOD1G93A mice. Finally, we assessed the 18 circRNAs with the largest expression differences and the highest degree of interspecies conservation in brain samples from sporadic ALS (sALS) patients and healthy controls. Similar to the mouse model, circRNA levels tended to decrease in the CNS of sALS patients.

CONCLUSIONS: Expression of circRNAs may be systematically altered in the two tissues most affected by ALS in a progressive and opposed manner. Although more detailed studies are warranted, circRNAs are potentially related to ALS etiopathogenesis and could possibly serve as future biomarkers, therapeutic targets, or customized therapeutic tools to modulate the pathology.}, } @article {pmid40595276, year = {2025}, author = {Sancho-Cantus, D and Sanchis, ES and Casani-Cubel, J and Privado, J and Escriba, J and Carriquí-Suárez, AB and Benlloch, M and Cerón, JJ and Rubio, CP and Cubero-Plazas, L and de la Rubia Ortí, JE}, title = {Prediction of antioxidant capacity, age, and sex on sleep impairment in patients with amyotrophic lateral sclerosis.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {21145}, pmid = {40595276}, issn = {2045-2322}, support = {2021-203-003//Universidad Católica de Valencia San Vicente Màrtir/ ; 2021-203-003//Universidad Católica de Valencia San Vicente Màrtir/ ; 2021-203-003//Universidad Católica de Valencia San Vicente Màrtir/ ; 2021-203-003//Universidad Católica de Valencia San Vicente Màrtir/ ; 2021-203-003//Universidad Católica de Valencia San Vicente Màrtir/ ; 2021-203-003//Universidad Católica de Valencia San Vicente Màrtir/ ; 2021-203-003//Universidad Católica de Valencia San Vicente Màrtir/ ; }, mesh = {Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Age Factors ; *Amyotrophic Lateral Sclerosis/complications/metabolism ; *Antioxidants/metabolism ; Cross-Sectional Studies ; Oxidative Stress ; Quality of Life ; Sex Factors ; *Sleep Wake Disorders/etiology ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterised by high levels of inflammation and oxidative stress, predominantly affecting males, particularly those between the ages of 50 and 65 years. It is characterised by progressive loss of motor neurones, leading to both motor and non-motor symptoms, such as sleep impairment, diagnosed in most patients, which adversely affects their quality of life. Therefore, this study aimed to determine the predictive role of antioxidant capacity, psychological distress, age, and sex on sleep impairment in an adult population of patients with ALS. A descriptive, quantitative, cross-sectional study was conducted using a sample of 74 patients diagnosed with bulbar or spinal ALS. To assess sleep disturbances in these patients, the Pittsburgh sleep quality index (PSQI), epworth sleepiness scale (ESS), and Insomnia severity index were used. Additionally, plasma antioxidant capacity was analysed using the total antioxidant capacity (TEAC), Cupric Ion reducing antioxidant capacity (CUPRAC), and ferric reducing power (FRAP). Anxiety and depression measures were used to measure psychological distress. Men exhibited a higher antioxidant status (lower oxidative stress) than women, and higher antioxidant capacity was associated with fewer sleep impairments (β = -0.43). Psychological distress may increase sleep impairment (β = -0.26). Furthermore, older individuals experienced less sleep impairment (β = -0.27), while sex had minimal influence on sleep deterioration, although it appears that men had fewer disturbances (β = -0.12). Having a higher antioxidant status, lower psychological distress, being male, and being older seem to act as predictors of reduced sleep impairment in ALS. Specifically, these four predictors account for 32% of sleep deterioration.Clínical trial registration: The present descriptive, quantitative, cross-sectional study was part of a clinical trial involving ALS patients, registered under the number NCT04654689 (https://clinicaltrials.gov/study/NCT04654689#wrapper).}, } @article {pmid40594383, year = {2025}, author = {Bernardi, S and Vitolo, S and Gabellini, C and Marchese, M and Ferraro, E}, title = {Trimetazidine stimulates intracellular Ca[2+] transients and zebrafish locomotor activity in spinal neurons.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {22854}, pmid = {40594383}, issn = {2045-2322}, support = {GSA23C003//Telethon Foundation/ ; AFM 23771//AFM-TELETHON/ ; P2022LSW98//PRIN 2022 PNRR/ ; }, mesh = {Animals ; Zebrafish/physiology ; *Calcium/metabolism ; Animals, Genetically Modified ; *Motor Neurons/drug effects/metabolism ; *Locomotion/drug effects ; *Trimetazidine/pharmacology ; *Spinal Cord/drug effects/cytology/metabolism ; *Calcium Signaling/drug effects ; }, abstract = {The metabolic modulator trimetazidine (TMZ) is an antianginal recently found to improve skeletal muscle performance in mice models of sarcopenia and of amyotrophic lateral sclerosis (ALS). The mechanism underlying the effect of TMZ on locomotor activity has been proposed to rely on its ability to enhance metabolic efficiency with a consequent improvement of myogenesis and of neuromuscular junction (NMJ) and muscle function. However, although promising and therefore under clinical trials, the mechanism of action of TMZ has not been clearly disclosed; here we hypothesized that it might involve the modulation of neuronal Ca[2+] flows. We studied the effect of TMZ on Ca[2+] dynamics in vivo, by using the transgenic zebrafish line Tg(neurod1:GCaMP6f) in which the neuronal expression of the Ca[2+] indicator GCaMP allows to visualize Ca[2+] dynamics in neurons of zebrafish larvae. By this elegant tool, we demonstrated, for the first time, that TMZ promotes an increase of intracellular Ca[2+] transients in zebrafish spinal neurons likely enhancing motor neuron firing, which correlates with enhanced motor performance induced by this drug. Even though elevated intracellular Ca[2+] levels have often been associated to neurotoxicity, it is unclear if the neuronal excitability features in some neuro-muscular disorders are compensatory or pathological. Therefore, this newly reported effect of TMZ which transiently and selectively enhances spinal neuron firing deserves to be further detailed and taken into account when the possible repurposing of this drug is proposed for the treatment of neuro-muscular disorders.}, } @article {pmid40593943, year = {2025}, author = {Gbadamosi, I and Binias, S and Gielniewski, B and Magno, R and Duarte, I and Jawaid, A}, title = {Coding and non-coding RNA expression in NSC34 cells following TDP-43 depletion and mutant TDP-43 M337V expression.}, journal = {Scientific data}, volume = {12}, number = {1}, pages = {1110}, pmid = {40593943}, issn = {2052-4463}, support = {TREMENDOS; UMO-2022/04/Y/NZ5/00122//EU Joint Programme - Neurodegenerative Disease Research (Programi i Përbashkët i BE-së për Kërkimet mbi Sëmundjet Neuro-degjeneruese)/ ; }, mesh = {*DNA-Binding Proteins/genetics ; Mutation ; *Amyotrophic Lateral Sclerosis/genetics ; Mice ; *Motor Neurons/metabolism ; Animals ; Humans ; Cell Line ; *RNA, Untranslated/genetics ; Transcriptome ; RNA Interference ; }, abstract = {Several neurodegenerative disorders (NDDs), notably amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) are characterized by pathological cytoplasmic aggregation of TAR DNA-binding protein 43 (TDP-43) in neurons and glia. Primarily localized in the nucleus under physiological conditions, TDP-43 is a critical regulator of RNA processing and metabolism. Therefore, RNA changes induced by TDP-43 depletion or mutation could play an important role in the pathogenesis of ALS and other TDP-43 related NDDs.To investigate these effects in NSC34 motor neuron-like cells, a commonly used cellular model of ALS, we used RNA interference to knock down TDP-43 and overexpressed the ALS-associated TDP-43 M337V mutation. RNA from both these experiments was enriched for small and large transcripts and subsequently analyzed via next-generation sequencing.The resulting transcriptomics datasets offer a valuable resource for studying the impact of TDP-43 depletion and mutant over-expression in motor neurons. These data enable comprehensive differential expression analyses and functional enrichment studies, identifying cellular pathways affected by TDP-43 depletion or mutation. Additionally, the inclusion of non-coding RNAs facilitates the construction of gene regulatory networks, providing insights into the interplay between coding and non-coding RNAs in gene expression regulation under TDP-43 loss-of-function or pathogenic mutation conditions.}, } @article {pmid40590340, year = {2025}, author = {Takahashi, F and Genge, A and Hirai, M and Selness, D and Todorovic, V and Wamil, A and Sasson, N and Apple, S and Ushirogawa, Y}, title = {Analysis of Long-Term Function and Survival of Edaravone Oral Suspension-Treated Patients With Amyotrophic Lateral Sclerosis Using PRO-ACT Data as Historical Placebo Controls.}, journal = {Muscle & nerve}, volume = {}, number = {}, pages = {}, doi = {10.1002/mus.28462}, pmid = {40590340}, issn = {1097-4598}, support = {//Mitsubishi Tanabe Pharma America, Inc./ ; }, abstract = {INTRODUCTION/AIMS: On/Off dosing of intravenous (IV) edaravone and edaravone oral suspension was US Food and Drug Administration (FDA)-approved for Amyotrophic Lateral Sclerosis (ALS) treatment. Placebo-controlled trials showed that IV edaravone slows the rate of physical functional decline in patients with ALS. Here, the impact of edaravone oral suspension on function and survival was assessed.

METHODS: Edaravone oral suspension was investigated in clinical trials MT-1186-A01/A02/A03/A04. Patients from Studies MT-1186-A02/A04 (prespecified analysis) and Studies MT-1186-A01/A02/A03/A04 (post hoc analysis) were propensity score matched 1:1 on 10 baseline variables with historical Pooled Resource Open-Access ALS Clinical Trials (PRO-ACT) placebo patients (not receiving active investigational treatment in their trials) to assess the impact of edaravone oral suspension on function and survival.

RESULTS: In the prespecified analysis, 78 edaravone oral suspension-treated patients from Studies MT-1186-A02/A04 demonstrated a survival benefit versus 78 matched PRO-ACT placebo patients (p = 0.005). Baseline risk-adjusted hazard ratio showed an 84% decreased risk of death in edaravone oral suspension versus PRO-ACT placebo patients (p = 0.005). ALS Functional Rating Scale-Revised (ALSFRS-R) total score change from baseline at Week 48 was -8.4 points for edaravone oral suspension versus -14.1 points for PRO-ACT placebo patients (p < 0.001). In the post hoc analysis, patients from Studies MT-1186-A01/A02/A03/A04 (n = 210) propensity score matched to PRO-ACT placebo patients (n = 210) showed statistically significantly longer time to death and smaller ALSFRS-R change from baseline at Week 48; restricted mean survival time showed a 7.3-month improvement (p < 0.001).

DISCUSSION: This suggests edaravone oral suspension significantly increases survival time and decreases physical functional decline versus PRO-ACT placebo patients.}, } @article {pmid40589992, year = {2025}, author = {Yue, Y and Chang, N and Shi, Z}, title = {Nonlinear characteristics of gait signals in neurodegenerative diseases.}, journal = {Frontiers in neurology}, volume = {16}, number = {}, pages = {1607273}, pmid = {40589992}, issn = {1664-2295}, abstract = {Based on the asymmetric characteristics of left and right movements in patients with neurodegenerative diseases and their inherent coupling relationships, as well as the inevitable internal connection between them according to the principles of mechanical kinematics, and a processing method for the ratio of gait signals to left and right limb data is proposed. Using gait time series data collected from left and right limbs via pressure-sensitive insoles, a comparison was conducted among patients with Parkinson's disease (PD), Amyotrophic Lateral Sclerosis (ALS), Huntington's disease (HD), and a healthy control group (Ctrl) in terms of the average, standard deviation, and coefficient of variation of the left and right sequences, as well as the ratios between them. It was discovered that there exists a close correlation between the ratios of left to right sequences and the actual standard deviation and coefficient of variation of these sequences. These ratios can be utilized for identifying the categories of PD, ALS, and HD patients. After using a median filter (n = 3) to filter four sets of stride ratio data (Ctr1, A1s, PD, and HD), it was found that the data before filtering generally showed significant fluctuations, with many peaks and valleys, indicating that the original data may contain a lot of noise or outliers. In contrast, the filtered data showed relatively smaller fluctuations and a smoother curve, indicating that the filtering process effectively reduced noise in the data and enhanced its stability. The raw data distribution for the left and right limbs of patients with PD, ALS, HD, and the Ctrl was relatively large, posing certain difficulties in analyzing the patients' diseases. The use of the ratio of left to right data effectively improves the discreteness of the data. The ranking of CO complexity features from highest to lowest is ALS, HD, PD, and Ctrl. The ranking of sample entropy features from largest to smallest is ALS, HD, PD, and Ctrl. The ranking of wavelet coefficient features from largest to smallest is ALS, PD, HD, and Ctrl.}, } @article {pmid40589786, year = {2025}, author = {Arreola-Aldape, CA and Moran-Guerrero, JA and Pons-Monnier, GK and Flores-Salcido, RE and Martinez-Ledesma, E and Ruiz-Manriquez, LM and Razo-Alvarez, KR and Mares-Custodio, D and Avalos-Montes, PJ and Figueroa-Sanchez, JA and Ortiz-Lopez, R and Martínez, HR and Cuevas-Diaz Duran, R}, title = {A systematic review and functional in-silico analysis of genes and variants associated with amyotrophic lateral sclerosis.}, journal = {Frontiers in neuroscience}, volume = {19}, number = {}, pages = {1598336}, pmid = {40589786}, issn = {1662-4548}, abstract = {INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a fatal progressive neurodegenerative disease characterized by the deterioration of upper and lower motor neurons. Affected patients experience progressive muscle weakness, including difficulty in swallowing and breathing; being respiratory failure the main cause of death. However, there is considerable phenotypic heterogeneity, and its diagnosis is based on clinical criteria. Moreover, most ALS cases remain unexplained, suggesting a complex genetic background.

METHODS: To better understand the molecular mechanisms underlying ALS, we comprehensively analyzed, filtered and classified genes from 4,293 abstracts retrieved from PubMed, 7,343 variants from ClinVar, and 33 study accessions from GWAS catalog. To address the importance of ALS-associated genes and variants, we performed diverse bioinformatic analyses, including gene set enrichment, drug-gene interactions, and differential gene expression analysis using public databases.

RESULTS: Our analysis yielded a catalog of 300 genes with 479 ALS-associated variants. Most of these genes and variants are found in coding regions and their proteins are allocated to the cytoplasm and the nucleus, underscoring the relevance of toxic protein aggregates. Moreover, protein-coding genes enriched ALS-specific pathways, for example spasticity, dysarthria and dyspnea. ALS-associated genes are targeted by commonly used drugs, including Riluzole and Edaravone, and by the recently approved antisense oligonucleotide therapy (Tofersen). Moreover, we observed transcriptional dysregulation of ALS-associated genes in peripheral blood mononuclear cell and postmortem cortex samples.

CONCLUSION: Overall, this ALS catalog can serve as a foundational tool for advancing early diagnosis, identifying biomarkers, and developing personalized therapeutic strategies.}, } @article {pmid40589421, year = {2025}, author = {Ravera, F and Efeoglu, E and Byrne, HJ}, title = {Monitoring the kinetic evolution of mesenchymal stem cell differentiation using Raman microspectroscopy.}, journal = {The Analyst}, volume = {150}, number = {15}, pages = {3445-3456}, doi = {10.1039/d4an01509f}, pmid = {40589421}, issn = {1364-5528}, mesh = {*Spectrum Analysis, Raman/methods ; *Mesenchymal Stem Cells/cytology ; *Cell Differentiation ; Kinetics ; Animals ; Collagen/chemistry ; Chondrocytes/cytology ; Hydrogels/chemistry ; Least-Squares Analysis ; Cells, Cultured ; Chondrogenesis ; Humans ; }, abstract = {Raman microspectroscopy (RMS) offers a powerful, non-destructive approach for in situ monitoring of dynamic biochemical processes within cells. However, the ability to reliably data-mine the spectroscopic signatures and their evolution and extract meaningful information can be challenging. Multivariate Curve Resolution-Alternating Least Squares (MCR-ALS) regression analysis is a powerful chemometric technique that can potentially address this challenge by deconvoluting the spectra into individual component spectra, each representing a specific biochemical species, and regressing the solutions against kinetic constraints. In this study, MCR-ALS analysis was performed on spectral data of differentiation process of mesenchymal stem cells into chondrocytes, carried out on two different substrates, collagen 3-dimensional hydrogel and the conventional 2-dimensional culture model at time intervals of 1-7, 14, 21 days. The kinetic evolution of the chondrogenesis was modelled according to a phenomenological rate equation model, in an attempt to describe the biochemical evolution of the cell composition within the process. Moreover, the ability of the algorithm to faithfully extract the correct reaction rates and spectral profiles has been explored. The results indicated that the differentiation process originates in the nucleolar regions, subsequently extending to the nuclear and cytoplasmic compartments and corroborated a more rapid differentiation rate in cell cultures grown on 3D collagen hydrogels compared to 2D substrates. The combination of Raman microspectroscopy and MCR-ALS offers a powerful approach for elucidating the complex mechanisms underlying chondrogenesis and developing innovative strategies for regenerative medicine.}, } @article {pmid40589142, year = {2025}, author = {Tiwari, R and Paswan, A and Tiwari, G and Reddy, VJS and Posa, MK}, title = {Perspectives on Fecal Microbiota Transplantation: Uses and Modes of Administration.}, journal = {Zhongguo ying yong sheng li xue za zhi = Zhongguo yingyong shenglixue zazhi = Chinese journal of applied physiology}, volume = {41}, number = {}, pages = {e20250014}, doi = {10.62958/j.cjap.2025.014}, pmid = {40589142}, issn = {1000-6834}, mesh = {*Fecal Microbiota Transplantation/methods ; Humans ; *Gastrointestinal Microbiome ; Feces/microbiology ; *Nervous System Diseases/therapy ; }, abstract = {Fecal microbiota Transplantation (FMT), often referred to as stool transplantation, fecal transfusion, and fecal bacteria therapy, is considered one of the most medical innovations of the 20th century. Fecal microbiota Transplantation entails filtering and dilution of a healthy donor's feces before injecting it into the recipient's digestive system. In China, it was first administered orally in the fourth century for diarrhea and food poisoning under the name "Yellow Soup." It has recently been widely employed in a variety of clinical settings, including cases of Clostridium difficile infection that are recurring and resistant. By replacing the unhealthy intestinal microbiota with a healthy bacterial community, the FMT treatment aims to enhance the intestinal flora. It also looks at neurological conditions where alterations in gut microbiota are prevalent. We have discussed FMT in the context of its use in conditions affecting the nerve system, such as neurological and other conditions (multiple sclerosis, Parkinson's disease, Alzheimer's disease, stroke, epilepsy, Amyotrophic lateral sclerosis, Tourette syndrome, neuropathic pain, Huntington's diseases, etc.), as well as the role of gut microbiota in many neurological disorders.}, } @article {pmid40587877, year = {2025}, author = {Moalefshahri, R and Hashemy, SI and Hosseini, H and Sahebkar, A}, title = {Neuroprotective effect of Kaempferol through modulation of autophagy.}, journal = {Nutritional neuroscience}, volume = {}, number = {}, pages = {1-17}, doi = {10.1080/1028415X.2025.2524702}, pmid = {40587877}, issn = {1476-8305}, abstract = {Objective: Autophagy is a critical cellular mechanism that ensures the breakdown of damaged or unnecessary components. This process helps ensure cellular health by maintaining cellular balance, protecting cells from stress, and providing an alternative energy source during metabolic stress. Disruptions in autophagy have been linked to neurological disorders.Method: In this review, the neuroprotective effects of Kaempferol through autophagy modulation are elaborated. Methods: An electronic search in scientific databases was performed to find relevant studies exploring the neuroprotective effects of kaempferol mediated via modulation of autophagy.Results: Kaempferol, a natural flavonoid found in fruits, vegetables, and plant-based products like tea, has been shown to demonstrate a variety of health-promoting properties, including antimicrobial, antioxidant, and antiinflammatory effects. This review summarizes the current understanding of how Kaempferol modulates autophagy and discusses its potential impact on various neurological disorders, including Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis, ischemic stroke, and depression. Studies increasingly indicate that Kaempferol could be a vital factor in maintaining neural health by influencing autophagy mechanisms.Conclusion: Numerous studies have established Kaempferol's neuroprotective potential through autophagy regulation, which suggests opprotunities for potential therapeutic applications.}, } @article {pmid40587259, year = {2025}, author = {Hattori, Y and Kumashiro, M and Kumeta, H and Kyo, T and Kawagoe, S and Matsusaki, M and Saio, T}, title = {A Disease-Associated Mutation Impedes PPIA through Allosteric Dynamics Modulation.}, journal = {Biochemistry}, volume = {64}, number = {14}, pages = {2971-2975}, pmid = {40587259}, issn = {1520-4995}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/enzymology/metabolism ; Allosteric Regulation ; *Peptidylprolyl Isomerase/genetics/chemistry/metabolism ; *Mutation ; Kinetics ; NIMA-Interacting Peptidylprolyl Isomerase ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by motor neuron degeneration. Peptidylprolyl cis-trans isomerase A (PPIA) is a molecular chaperone involved in protein folding, and its dysfunction has been linked to ALS pathogenesis, as proline is recognized as a key residue for maintaining proper folding of ALS-related proteins. A recent study identified a K76E mutation in PPIA in sporadic ALS patients, but its effect on protein function and structure remain unclear. In this study, we used biochemical and biophysical techniques to investigate the structural and functional consequences of the K76E mutation. Our results show that K76E significantly reduces enzyme activity without affecting structure, monodispersity, or substrate recognition. Significant effects of K76E mutation were identified by relaxation dispersion NMR experiments, showing that K76E disrupts key protein dynamics and alters an allosteric network essential for isomerase activity. Corroborated by theoretical kinetic analysis, these dynamics data, revealing the exchange process for K76E to be approximately 1 order of magnitude slower than that of the wild type, explain the reduced cis-trans isomerase activity of the K76E mutant. These findings suggest that the pathogenic effect of K76E arises primarily from impaired protein dynamics rather than direct structural disruption. Our study provides new insights into the molecular mechanisms underlying ALS-associated mutations and their impact on protein function.}, } @article {pmid40587112, year = {2025}, author = {Regev, S and Talmy, T and Gelikas, S and Mitchnik, IY}, title = {Impact of ongoing clinical experience on advanced life support provider performance in multicasualty simulations.}, journal = {The journal of trauma and acute care surgery}, volume = {99}, number = {3S Suppl 1}, pages = {S32-S38}, doi = {10.1097/TA.0000000000004697}, pmid = {40587112}, issn = {2163-0763}, mesh = {Humans ; *Clinical Competence ; Israel ; *Advanced Trauma Life Support Care/standards ; *Simulation Training ; Male ; Female ; *Military Medicine/education ; Military Personnel ; Adult ; }, abstract = {BACKGROUND: Effective response to multicasualty events may depend on the performance of advanced life support (ALS) providers. This study examines the relationship between ALS training, clinical skill maintenance through a Competency Maintenance Program, and provider performance in multicasualty event simulations.

METHODS: Military medical teams, led by Israel Defense Forces (IDF) Military Trauma Life Support (MTLS)-trained providers (physicians or paramedics), participated in a multicasualty scenario simulation. Performance was assessed using a task checklist and the Trauma Non-Technical Skills scale. Data were collected on MTLS training and participation in the Competency Maintenance Program, which mandates ALS providers to complete hospital and ambulance shifts for continuous skill maintenance. Regression analyses were conducted to evaluate the impact of these variables on simulation performance.

RESULTS: The study included 25 teams, the majority of which were led by paramedics (78%). Clinical experience in hospitals and ambulance services showed moderate correlations with simulation performance (R = 0.562, p = 0.009, and R = 0.664, p = 0.003, respectively). However, ALS provider type (physician vs. paramedic) and MTLS course performance did not correlate with simulation performance (R = 0.009, p = 0.952, and R = 0.390, p = 0.054, respectively). Simulation performance was also correlated with the teams' nontechnical skills (R = 0.550, p < 0.001, β = 0.393, p = 0.014), which functioned as both an independent factor and a partial mediator in the relationship between ALS providers' attributes and simulation performance (R2 = 0.725, R2 change = 0.475). Specifically, clinical experience in hospitals was directly linked to performance, whereas ambulance experience was indirectly associated with performance through its impact on nontechnical skills.

CONCLUSION: Clinical skill maintenance through hospital and ambulance experience may enhance ALS providers' performance in multicasualty event simulations. These findings suggest that structured skill maintenance programs could better prepare teams for managing complex scenarios.

LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level III.}, } @article {pmid40586230, year = {2025}, author = {Knudsen, LF and Nikolajevic-Pujic, S}, title = {Prevalence and predictors of prolonged grief disorder, anxiety and depression in bereaved ALS family caregivers: a national survey of distress and support needs after bereavement.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {}, number = {}, pages = {1-12}, doi = {10.1080/21678421.2025.2523948}, pmid = {40586230}, issn = {2167-9223}, abstract = {OBJECTIVE: The distress of amyotrophic lateral sclerosis (ALS) family caregivers may not end after bereavement. Yet, the prevalence of psychological distress and support needs after bereavement are unclear. This study examined the prevalence and predictors of prolonged grief disorder (PGD), anxiety and depression, and level of needed and received support after bereavement.

METHODS: We conducted a cross-sectional online survey of a national cohort of bereaved ALS family caregivers recruited through the National Rehabilitation Center for Neuromuscular Diseases in Denmark. Questions included disease-related factors, care involvement, burden (Zarit Burden Inventory), loneliness (Three-Item Loneliness Scale), coping style (CSQ-37), PGD (PG-13), anxiety/depression (HADS), time since bereavement, needed and received support during and after ALS.

RESULTS: A total of 162 caregivers (46.4%) with a median of 24 months since bereavement responded. PGD prevalence was 5.6%, anxiety 22.2%, depression 16.0%. PGD was predicted by more caregiving hours. Anxiety and depression by high emotional coping and not receiving the needed information post bereavement and, anxiety, also by a more recent bereavement. Half of the participants had needed information about ALS after bereavement with 17.4% receiving it to a small degree and 32.3% not at all. Nearly 80% had needed emotional support with 31.0% receiving it to a small degree/not at all.

CONCLUSIONS: Caregivers may be distressed for a long time. Healthcare professionals should offer information about ALS to bereaved caregivers and screen caregivers for PGD, anxiety, depression, and coping style to offer targeted interventions post bereavement. Future longitudinal studies should investigate predictors for post-loss psychological distress including pre-loss anxiety/depression and formal care.}, } @article {pmid40586110, year = {2025}, author = {Appukuttan, S and Grapperon, AM and El Mendili, MM and Dary, H and Guye, M and Verschueren, A and Ranjeva, JP and Attarian, S and Zaaraoui, W and Gilson, M}, title = {Evaluating machine learning pipelines for multimodal neuroimaging in small cohorts: an ALS case study.}, journal = {Frontiers in neuroinformatics}, volume = {19}, number = {}, pages = {1568116}, pmid = {40586110}, issn = {1662-5196}, abstract = {Advancements in machine learning hold great promise for the analysis of multimodal neuroimaging data. They can help identify biomarkers and improve diagnosis for various neurological disorders. However, the application of such techniques for rare and heterogeneous diseases remains challenging due to small-cohorts available for acquiring data. Efforts are therefore commonly directed toward improving the classification models, in an effort to optimize outcomes given the limited data. In this study, we systematically evaluated the impact of various machine learning pipeline configurations, including scaling methods, feature selection, dimensionality reduction, and hyperparameter optimization. The efficacy of such components in the pipeline was evaluated on classification performance using multimodal MRI data from a cohort of 16 ALS patients and 14 healthy controls. Our findings reveal that, while certain pipeline components, such as subject-wise feature normalization, help improve classification outcomes, the overall influence of pipeline refinements on performance is modest. Feature selection and dimensionality reduction steps were found to have limited utility, and the choice of hyperparameter optimization strategies produced only marginal gains. Our results suggest that, for small-cohort studies, the emphasis should shift from extensive tuning of these pipelines to addressing data-related limitations, such as progressively expanding cohort size, integrating additional modalities, and maximizing the information extracted from existing datasets. This study provides a methodological framework to guide future research and emphasizes the need for dataset enrichment to improve clinical utility.}, } @article {pmid40585924, year = {2025}, author = {Almuhanna, Z and Bohulaigah, Z and Alkhawaja, H and Aljafar, H}, title = {Posterior trachea wall erosion: a case report and literature review of a catastrophic complication of cuff overinflation.}, journal = {Journal of surgical case reports}, volume = {2025}, number = {6}, pages = {rjaf361}, pmid = {40585924}, issn = {2042-8812}, abstract = {Tracheostomy complications range from early to late complications. One of the late complications can be seen with cuff over-inflation that exceeds tracheal capillary perfusion pressure, which leads to segmental tracheomalacia and rarely, tracheal wall erosion. A 40-year-old male with amyotrophic lateral sclerosis and mechanical ventilation dependence was found to have a persistent ventilatory leak. Endoscopic examination revealed a large posterior tracheal wall erosion that was confirmed by computed tomography. Conservative management by the placement of a long endotracheal tube through the tracheostoma was chosen. Cuff pressure over 20-25 cm H2O, which exceeds tracheal capillary perfusion pressure, increases the risk of tracheal mucosal ischemia. Preventive strategies such as the use of pressure-limiting devices and careful tube selection, should be implemented. Regular implementation of preventive measures along with early identification are essential for avoiding tracheostomy tube complications. This case demonstrates the importance of strict cuff pressure maintenance to avoid tracheal wall injuries.}, } @article {pmid40585812, year = {2025}, author = {Barbier, M and Gareau, T and Camuzat, A and Guillaud-Bataille, M and Boluda, S and Clot, F and Araktingi, L and Borroni, B and van der Zee, J and Ghidoni, R and Bellini, S and Galimberti, D and Rossi, G and Nacmias, B and De la Casa-Fages, B and Pastor, P and , and Latouche, M and le Guern, E and Durr, A and Laquerrière, A and Moccia, R and Seilhean, D and Alvarez, V and Le Ber, I}, title = {Analysis of short tandem repeats linked to polyglutamine diseases from whole-genome sequencing reveals intermediate alleles of HTT associated with an early disease onset in C9orf72 carriers.}, journal = {Brain communications}, volume = {7}, number = {3}, pages = {fcaf220}, pmid = {40585812}, issn = {2632-1297}, abstract = {Carriers of the GGGGCC pathogenic expansion in C9orf72 can develop symptoms of frontotemporal dementia and/or amyotrophic lateral sclerosis, with variable and unpredictable ages at onset. Previous studies aiming to decipher the genetic bases of the clinical variability in this rare disease included bi-allelic polymorphisms, excluding short tandem repeats. Whole-genome sequencing data of 195 C9orf72 patients were used to consider all short tandem repeats linked to polyglutamine disorders as potential genetic modifiers given the existing links between C9orf72 and polyglutamine diseases. Intermediate alleles of HTT encoding huntingtin were associated with an earlier age at onset among C9orf72 carriers in the discovery cohort (n = 195, P = 0.0003) and in a European replication cohort (n = 145, P = 0.006). In the merged cohort (n = 340), the average difference of age at disease onset was 9.42 ± 2.14 years (P = 1.3 × 10[e-5]) between carriers and non-carriers of HTT-intermediate alleles. Neuropathology of one C9orf72 case heterozygous for HTT-intermediate allele showed typical TDP-43 inclusions related to the C9orf72 pathogenic expansion and was negative for polyglutamine inclusion. No somatic expansion of HTT was detected in blood of all C9orf72exp/HTT-intermediate carriers. If this study reinforces potential biological links between huntingtin and C9orf72 that remain to be explored, the results also illustrate the interest of considering short tandem repeats from whole-genome data in association studies which paves the way to more exhaustive approaches to explore the trait heritability due to short-tandem-repeats still hidden in the genome.}, } @article {pmid40585720, year = {2025}, author = {Kato, T and Yorimoto, K and Ariake, Y and Shimizu-Motohashi, Y and Hara, T}, title = {Acute Respiratory Distress Syndrome Exacerbated by Inappropriate Use of Mechanical Insufflation-Exsufflation Following Infection in a Patient With Amyotrophic Lateral Sclerosis: A Case Report.}, journal = {Cureus}, volume = {17}, number = {5}, pages = {e84991}, pmid = {40585720}, issn = {2168-8184}, abstract = {Mechanical insufflation-exsufflation (MI-E) is widely used to assist airway secretion clearance in patients with neuromuscular disorders such as amyotrophic lateral sclerosis (ALS). While MI-E is generally considered safe when used intermittently for cough augmentation, its prolonged and unsupervised use as a substitute for invasive ventilation is discouraged by current clinical guidelines, including those issued by the American College of Chest Physicians and the American Academy of Neurology. We report the case of a 53-year-old man with advanced ALS, diagnosed approximately 10 years earlier, who developed acute respiratory distress syndrome (ARDS) exacerbated by inappropriate use of MI-E following a recent respiratory infection. The patient had previously relied on tracheostomy invasive ventilation (TIV) but chose to suspend its use, instead employing MI-E continuously for 62 hours (28,234 cycles), based on prior positive experiences and personal preference. Upon hospital admission, the patient was diagnosed with mild ARDS, bacterial pneumonia, and influenza B infection. Although the respiratory infection was likely the primary cause of deterioration, MI-E-related pressure changes may have exacerbated pulmonary injury, particularly in the context of acute infection. Rapid improvement in gas exchange and imaging findings within 48 hours of MI-E discontinuation further supports this hypothesis. We discuss possible mechanisms linking excessive MI-E usage to lung injury, including barotrauma and negative pressure pulmonary edema. We also emphasize the importance of clearly defined device indications, structured caregiver education, and regular clinical supervision in home respiratory care. To our knowledge, this may be the first reported case of ARDS potentially resulting from the combined effects of infection and inappropriate MI-E application, highlighting the need for multidisciplinary coordination and proper device supervision in managing advanced neuromuscular respiratory failure at home.}, } @article {pmid40585388, year = {2025}, author = {Wang, X and Sun, Y and Han, C and Meng, X and Wen, K and Wu, J and Min, P and Li, K and Zhang, Y}, title = {Research trends of piezoelectric materials in neurodegenerative disease applications.}, journal = {Bioactive materials}, volume = {52}, number = {}, pages = {366-392}, pmid = {40585388}, issn = {2452-199X}, abstract = {Neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and huntington's disease, pose significant threats to human health, with current treatment options remaining limited. Piezoelectric materials, known for their ability to convert mechanical energy into electrical signals at the nanoscale, hold great promise in the diagnosis and treatment of neurodegenerative diseases due to their excellent electromechanical properties, environmental stability, and sensitivity. This review systematically outlines the working principles and classifications of piezoelectric materials. Subsequently, the recent advances in piezoelectric materials and their applications in the diagnosis and treatment of neurodegenerative diseases are highlighted. Finally, the challenges and perspectives regarding the development of future piezoelectric materials are discussed. This review aims to provide a comprehensive reference for the further application of piezoelectric materials in neurodegenerative diseases.}, } @article {pmid40585370, year = {2025}, author = {Maurel, C and Scherer, NM and Luu, L and Radford, RA and Hogan, A and Merjane, J and Vidal-Itriago, A and Don, EK and Chapman, T and Cull, S and Vourc'h, P and Lisowski, L and Lee, A and Chung, RS and Morsch, M}, title = {Critical impact of lysine 136 in TDP-43 phase separation, compartmentalization, and aggregation in living vertebrates.}, journal = {iScience}, volume = {28}, number = {7}, pages = {112761}, pmid = {40585370}, issn = {2589-0042}, support = {R21 DA056320/DA/NIDA NIH HHS/United States ; }, abstract = {TDP-43 is a nuclear RNA-binding protein that undergoes liquid-liquid phase separation (LLPS) and forms insoluble aggregates in neurodegenerative diseases. By studying TDP-43 in living vertebrates, we confirmed that TDP-43 undergoes LLPS and forms dynamic biomolecular condensates in spinal motor neurons. We validated in vivo that interfering with the lysine residue at position 136 altered the phase separation behavior of TDP-43 by reducing cytoplasmic mislocalization and aggregation. These alterations were post-translational modification (PTM) independent, highlighting that residue 136 is a key structural regulator of TDP-43 function. We further established an adeno-associated virus (AAV)-mediated expression approach in mice that confirmed altered nuclear condensation characteristics of lysine-modified TDP-43. These assessments exposed the formation of dynamic nuclear TDP-43 condensates and emphasize the important role of lysine 136 in maintaining TDP-43 function. Altogether, we establish lysine 136 as a molecular regulator for phase separation and TDP-43 aggregation in amyotrophic lateral sclerosis (ALS) in two in vivo platforms.}, } @article {pmid40585363, year = {2025}, author = {Wang, C and Xu, J and Pan, K and Xu, Y and Yu, J}, title = {Relationship between endocrine disruptors and neurodegenerative diseases: Systematic review and meta-analysis.}, journal = {iScience}, volume = {28}, number = {7}, pages = {112779}, pmid = {40585363}, issn = {2589-0042}, abstract = {We conducted a meta-analysis to evaluate relevant literature published between January 2003 and December 2023 in order to provide updated epidemiological evidence on the relationship between endocrine-disrupting chemicals (EDCs) and neurodegenerative diseases (NDs). A systematic search of related studies was conducted in PubMed, Web of Science, and Embase. A total of 21 studies were included, with 286,610 subjects for meta-analysis. Analysis revealed that exposure to polychlorinated biphenyls (odds ratio [OR] = 1.08, 95% confidence interval [CI]: 1.03-1.14) posed a risk for NDs, while organochlorine pesticide (OR = 1.11, 95% CI: 1.05-1.17) exposure exhibited a positive correlation with ND risk. Subgroup analysis by disease indicated a positive association between EDC exposure and Alzheimer's disease (OR = 1.03, 95% CI: 1.00-1.07) and amyotrophic lateral sclerosis (OR = 1.02, 95% CI: 1.01-1.03) risk. Our meta-analysis indicates that human exposure to EDCs has adverse effects on NDs.}, } @article {pmid40585304, year = {2025}, author = {Cesaro, G and Baruzzo, G and Tussardi, G and Di Camillo, B}, title = {Differential cellular communication inference framework for large-scale single-cell RNA-sequencing data.}, journal = {NAR genomics and bioinformatics}, volume = {7}, number = {2}, pages = {lqaf084}, pmid = {40585304}, issn = {2631-9268}, mesh = {*Single-Cell Analysis/methods ; *Cell Communication/genetics ; Humans ; *Sequence Analysis, RNA/methods ; *Transcriptome ; *Software ; Gene Expression Profiling/methods ; Computational Biology/methods ; }, abstract = {Single-cell transcriptomics data have been widely used to characterize biological systems, particularly in studying cell-cell communication, which plays a significant role in many biological processes. Despite the availability of various computational tools for inferring cellular communication, quantifying variations across different experimental conditions at both intercellular and intracellular levels remains challenging. Moreover, available methods are in general limited in terms of flexibility in analyzing different experimental designs and the ability to visualize results in an easily interpretable way. Here, we present a generalizable computational framework designed to infer and support differential cellular communication analysis across two experimental conditions from large-scale single-cell transcriptomics data. The scSeqCommDiff tool employs a statistical and network-based computational approach for characterizing altered cellular cross-talk in a fast and memory-efficient way. The framework is complemented with CClens, a user-friendly Shiny app to facilitate interactive analysis of inferred cell-cell communication. Validation through spatial transcriptomics data, comparison with other tools, and application to large-scale datasets (including a cell atlas) confirms the reliability, scalability, and efficiency of the framework. Moreover, the application to a single-nucleus transcriptomics dataset shows the validity and ability of the proposed workflow to support and unravel alterations in cell-cell interactions among patients with amyotrophic lateral sclerosis and healthy subjects.}, } @article {pmid40585174, year = {2025}, author = {Cassel, R and Lorenc, F and Bombardier, A and DE Tapia, C and Dieterle, S and Gouveia Roque, C and Jackson, CA and Stuart-Lopez, G and Rouaux, C and Guillot, SJ and Birling, MC and Kessler, P and Grassano, M and Traynor, B and Chio, A and Roy, R and Shorter, J and Waldron, FM and Gregory, JM and Phatnani, H and Dupuis, L and Megat, S}, title = {FUS Mislocalization Rewires a Cortical Gene Network to Drive Cognitive and Behavioral Impairment in ALS.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, pmid = {40585174}, support = {ZIA AG000933/ImNIH/Intramural NIH HHS/United States ; }, abstract = {Cognitive and behavioral impairment affects up to half of individuals with amyotrophic lateral sclerosis (ALS), but their molecular origin remains unresolved. Here, we identify mislocalization of the RNA-binding protein FUS in cortical neurons as a defining feature in ALS patients with cognitive impairment (ALS-ci). Selective mislocalization of FUS in adult cortical projection neurons in mice is sufficient to trigger ALS-ci- and ALS with behavioral impairment (ALS-bi)-like phenotypes, including deficits in sociability, and neurodegeneration. Single-nucleus transcriptomics reveal a conserved FUS-dependent gene network downregulated in these mice and ALS-ci patients. This regulon is enriched for ALS genetic risk factors and newly implicates FBXO16 in ALS-bi. Carriers of protein-truncating FBXO16 variants display behavioral abnormalities, frontotemporal atrophy, and increased levels of dementia-linked biomarkers. These findings define a neuron-intrinsic mechanism for cognitive and behavioral dysfunction in ALS and nominate FUS mislocalization and its downstream gene network as therapeutic targets.}, } @article {pmid40585089, year = {2025}, author = {Shen, T and Spencer, BE and Kuksa, PP and Van Deerlin, VM and Phatnani, H and , and Lee, EB and McMillan, CT}, title = {Unraveling temporal dynamics of the post-mortem transcriptome in amyotrophic lateral sclerosis.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, doi = {10.1101/2025.06.10.25329061}, pmid = {40585089}, abstract = {Human tissue transcriptomics are crucial for understanding neurodegeneration but limited by cross-sectional post-mortem sampling, which represents end-stage disease. Subtype and Stage Inference (SuStaIn) modeling addresses these limitations by inferring temporal gene expression dynamics while also identifying potential transcriptomic subtypes. Applied to bulk RNA-seq data from post-mortem lumbar spinal cord in amyotrophic lateral sclerosis (ALS), SuStaIn unraveled that more advanced transcriptomic stages were associated with higher microglia and reduced neuron proportions, which mapped onto two ALS subtypes: Immune/Apoptosis/Proteostasis subtype with early immune/apoptotic/proteostatic dysregulation, worse prognosis and higher microglia proportions; Synapse/RNA-Metabolism subtype with early synaptic/RNA-processing deficits, lower male prevalence and neuron loss. Lumbar patterns demonstrated high concordance with cervical patterns and a strong correlation in staging across regional tissues. These findings revealed subtype-specific mechanisms underlying ALS heterogeneities, prioritized key genes driving subtyping/staging as potential therapeutic targets. More broadly, we established a framework to decode temporal dynamics from traditionally constrained post-mortem transcriptomic studies.}, } @article {pmid40584972, year = {2025}, author = {Khandelwal, N and Sanchirico, M and Ajibade, A and Munshi, K and Vu, M and Engel-Nitz, N and Steiger, C and Anderson, AJ and Karam, C}, title = {Characteristics, Treatment Patterns, Healthcare Resource Utilization, and Costs Among Patients with Multifocal Motor Neuropathy: A US Claims Database Cohort Study.}, journal = {Journal of health economics and outcomes research}, volume = {12}, number = {1}, pages = {261-268}, pmid = {40584972}, issn = {2327-2236}, abstract = {Background: Multifocal motor neuropathy (MMN) is a rare, slowly progressive nerve disorder characterized by asymmetric limb weakness without sensory abnormalities. MMN is often misdiagnosed due to similarities in clinical symptoms with conditions including amyotrophic lateral sclerosis (ALS), making diagnosis and treatment challenging. Objectives: This study assessed patient characteristics, treatment patterns, and the economic burden of MMN in the United States. Methods: Using the Optum Research Database, this retrospective analysis included patients with ≥1 diagnostic or nondiagnostic medical claim with an MMN diagnosis code between 2016 and 2020 (date of first diagnosis-related claim =index date), and continuous enrollment for 12 months preindex and postindex. Patients with MMN within this group were identified using more specific criteria; ≥2 MMN nondiagnostic claims separated by ≥30 days, with no subsequent ALS diagnosis during follow-up. All patients who did not meet these criteria were included in the MMN-mimic cohort. Outcomes included treatment patterns, differential diagnoses, healthcare utilization, and costs. Results: Of 904 patients identified, 37% had MMN and 63% had an MMN-mimic condition. Patients with MMN were significantly younger than patients in the MMN-mimic cohort (mean, 64.9 vs 66.8 years; P = .047). At preindex, significantly more patients with MMN received MMN-related medications than patients in the MMN-mimic cohort (20.5% vs 9.0%, respectively; P < .001). Intravenous immunoglobulin (IVIG) was the most common MMN-related medication. At postindex, more patients with MMN used IVIG (28.0%) compared with preindex (16.4%). In the 12 months preindex and postindex, >70% of patients had ≥1 differential diagnosis. The MMN cohort had higher all-cause total costs than the MMN-mimic cohort (mean preindex, 58 974 v s 48 132, respectively [P = .100]; mean postindex, 74 187 v s 50 652 [P = .002]); they also had significantly higher MMN-related healthcare costs (mean preindex, 23 625 v s 12 890 [P = .011]; mean postindex, 39 521 v s 11 938 [P < .001]). Discussion: This study showed that most patients with initial MMN diagnoses had an alternative disorder after subsequent evaluation/follow-up, and patients with MMN incurred higher costs. Many patients with MMN did not receive IVIG, suggesting that undertreatment or misattribution of diagnosis codes are common. Conclusions: Further education is needed regarding accurate diagnosis of MMN to ensure patient access to guideline-recommended treatment.}, } @article {pmid40584588, year = {2025}, author = {Odenbring, Y and Lindén, L}, title = {Reaching everyone: school nurses' experiences of including refugee and migrant students in the extended school-based HPV vaccination programme in Sweden.}, journal = {Journal of research in nursing : JRN}, volume = {}, number = {}, pages = {17449871251329001}, pmid = {40584588}, issn = {1744-988X}, abstract = {BACKGROUND: In Sweden, providing a free-of-charge national child vaccination programme is part of national public health work to promote health and prevent illness. Yet Sweden is no exception when it comes to systematic societal inequality. Research worldwide has shown that childhood vaccination coverage is lower among refugee and migrant children than among non-migrant children.

AIM: The aim of this study is to explore how school nurses working in one of Sweden's largest regions reflect on their strategies and experiences of including children with refugee or migrant backgrounds in the school-based extended HPV vaccination programme.

METHODS: The study draws from semi-structured individual interviews with 21 school nurses. Analysis drew on Braun et al's (2011) four contextual dimensions: 1) the situated context; 2) the professional context; 3) material contexts; 4) external contexts. Thematic analysis was undertaken (Braun and Clarke, 2006; Clarke and Braun, 2013).

RESULTS: Three themes were identified: 1) social and economic deprivation; 2) ways of communicating; 3) gratitude. According to the school nurses, mapping the families' social situation and building trusting relationships are essential. Providing written information about the vaccination in diverse languages and/or involving an interpreter are also important strategies to reach refugee and migrant parents. Despite the families' often marginalised position, the children and their parents favour the HPV vaccination, which could be interpreted as vaccine confidence.

CONCLUSIONS: Meeting the needs of children and families with refugee or migrant backgrounds requires that school nursing practice take a holistic perspective. The study contributes new insights regarding these issues.}, } @article {pmid40584177, year = {2025}, author = {Wu, Q and Yang, J and Duan, Y and Ma, Y and Zhang, Y and Tan, S and Wang, J and Wang, Y and Liu, B and Zhang, J and Liu, X}, title = {Environmental risk factors, protective factors, and biomarkers for amyotrophic lateral sclerosis: an umbrella review.}, journal = {Frontiers in aging neuroscience}, volume = {17}, number = {}, pages = {1541779}, pmid = {40584177}, issn = {1663-4365}, abstract = {INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the rapid loss of motor neurons. Given the significant global economic impact of ALS, effective preventive measures are urgently needed to reduce the incidence of this devastating disease. Recent meta-analyses have explored potential links between environmental factors, biomarkers, and ALS occurrence. However, the findings of these studies have been inconsistent and controversial. Therefore, we present a comprehensive umbrella review of recent meta-analyses to systematically summarize the available epidemiological evidence and evaluate its credibility.

METHODS: A systematic search was conducted in PubMed and Embase from inception until 01 October 2024, to identify meta-analyses of observational studies examining associations between environmental risk factors, protective factors, biomarkers, and ALS susceptibility. For each meta-analysis, summary effect estimates, 95% confidence intervals (CIs), 95% prediction intervals, study heterogeneity, small study effects, and excess significance biases were calculated independently by two investigators. The methodological quality was evaluated using the AMSTAR 2 criteria. The strength of the epidemiological evidence was categorized into five levels based on predefined criteria.

RESULTS: Out of 1,902 articles identified, 43 met the inclusion criteria, resulting in 103 included meta-analyses. These analyses covered 46 environmental risk and protective factors (344,597 cases, 71,415,574 population) and 57 cerebrospinal fluid (CSF) and serum biomarkers (30,941 cases, 2,180,797 population). The evidence was classified as convincing (Class I) for the regular use of antihypertensive drugs (OR: 0.85, 95% CI: 0.81-0.88) and highly suggestive (Class II) for premorbid body mass index (OR: 0.97, 95% CI: 0.95 to 0.98), trauma (OR: 1.51, 95% CI: 1.32 to 1.73), CSF NFL levels (SMD: 2.06, 95% CI: 1.61 to 2.51), serum NFL levels (SMD: 1.57, 95% CI: 1.29 to 1.85), ferritin levels (SMD: 0.66, 95% CI: 0.50 to 0.83), and uric acid levels (SMD: -0.72; 95% CI: -0.98 to -0.46).

DISCUSSION: This umbrella review offers new insights into the epidemiological evidence regarding the associations between environmental factors, biomarkers, and ALS susceptibility. We aim for our study to enhance the understanding of the roles of environmental factors and biomarkers in ALS occurrence and assist clinicians in developing evidence-based prevention and control strategies.}, } @article {pmid40583986, year = {2025}, author = {Shobe, SM and Melka, D and Mulugeta, M and Adane, L}, title = {Bright tongue sign as a radiological clue of bulbar onset amyotrophic lateral sclerosis: A case report.}, journal = {Radiology case reports}, volume = {20}, number = {9}, pages = {4338-4341}, pmid = {40583986}, issn = {1930-0433}, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by degeneration of motor neurons, with the tongue often involved in clinical presentation. In this case, a 60-year-old female presented with progressive choking episodes and speech slurring over 9 months, exhibiting dysarthria, prominent tongue atrophy, fasciculations, and hyperreflexia. Needle electromyography (EMG) showed diffuse chronic neurogenic changes with signs of active denervation changes prominent on the tongue and right arm with normal sensory nerve studies. Magnetic resonance imaging (MRI) brain imaging revealed a Diffuse T1 Weighted image (T1WI) hyperintense of tongue known as "bright tongue sign" indicating fatty infiltration of tongue muscles, consistent with neurogenic atrophy. This case underscores the importance of recognizing this characteristic tongue hyperintensity as a valuable radiological clue in diagnosing bulbar-onset ALS and highlights the potential for early diagnosis to improve patient management and outcomes.}, } @article {pmid40583561, year = {2025}, author = {Magarotto, M and Gawne, RT and Vilkaite, G and Beltrami, M and Mason, AS and Chen, HJ}, title = {Familial ALS/FTD-associated RNA-binding deficient TDP-43 mutants cause neuronal and synaptic transcript dysregulation in vitro.}, journal = {Human molecular genetics}, volume = {}, number = {}, pages = {}, doi = {10.1093/hmg/ddaf111}, pmid = {40583561}, issn = {1460-2083}, support = {SBF006\1088//British Heart Foundation and Diabetes UK/ ; //ASM's York Against Cancer (York, UK)/ ; }, abstract = {TDP-43 is an RNA-binding protein constituting the pathological inclusions observed in ~ 95% of ALS and ~ 50% of FTD patients. In ALS and FTD, TDP-43 mislocalises to the cytoplasm and forms insoluble, hyperphosphorylated and ubiquitinated aggregates that enhance cytotoxicity and contribute to neurodegeneration. Despite its primary role as an RNA/DNA-binding protein, how RNA-binding deficiencies contribute to disease onset and progression are little understood. Among many identified familial mutations in TDP-43 causing ALS/FTD, only two mutations cause an RNA-binding deficiency, K181E and K263E. In this study, we used CRISPR/Cas9 to knock-in the two disease-linked RNA-binding deficient mutations in SH-SY5Y cells, generating both homozygous and heterozygous versions of the mutant TDP-43 to investigate TDP-43-mediated neuronal disruption. Significant changes were identified in the transcriptomic profiles of these cells, in particular, between K181E homozygous and heterozygous cells, with the most affected genes involved in neuronal differentiation and synaptic pathways. This result was validated in cell studies where the neuronal differentiation efficiency and neurite morphology were compromised in TDP-43 cells compared to unmodified control. Interestingly, divergent neuronal regulation was observed in K181E-TDP-43 homozygous and heterozygous cells, suggesting a more complex signalling network associated with TDP-43 genotypes and expression level which warrants further study. Overall, our data using cell models expressing the ALS/FTD disease-causing RNA-binding deficient TDP-43 mutations at endogenous levels show a robust impact on transcriptomic profiles at the whole gene and transcript isoform level that compromise neuronal differentiation and processing, providing further insights on TDP-43-mediated neurodegeneration.}, } @article {pmid40583472, year = {2025}, author = {Salehirozveh, M and Dehghani, P and Mijakovic, I}, title = {Nanopore-Based Neurotransmitter Detection: Advances, Challenges, and Future Perspectives.}, journal = {ACS nano}, volume = {19}, number = {27}, pages = {24404-24424}, pmid = {40583472}, issn = {1936-086X}, mesh = {*Nanopores ; *Neurotransmitter Agents/analysis ; Humans ; *Nanotechnology/methods ; *Biosensing Techniques/methods ; Animals ; }, abstract = {Neurotransmitters play a pivotal role in neural communication, synaptic plasticity, and overall brain function. Disruptions in neurotransmitter homeostasis are closely linked to various neurological and neuropsychiatric disorders, including Alzheimer's disease, Parkinson's disease, epilepsy, schizophrenia, depression, and amyotrophic lateral sclerosis. This review explores the critical role of neurotransmitters in neurological disorders and highlights recent advances in nanopore-based neurotransmitter detection. Solid-state nanopores (SSNs), with their superior mechanical and chemical durability, have emerged as highly sensitive molecular sensors capable of real-time monitoring of neurotransmitter dynamics. We discuss the integration of SSNs into diagnostic frameworks, emphasizing their potential for early disease detection and personalized therapeutic interventions. Additionally, we examine the complementary role of nanopipettes in neurotransmitter detection, focusing on their high spatial resolution and real-time monitoring capabilities. The review also addresses the challenges and future perspectives of nanopore-based sensing technology, including the need for improved sensitivity, stability, and reproducibility. By integrating insights from neuroscience, bioengineering, and nanotechnology, this review aims to provide a comprehensive overview of how nanopore sensing can revolutionize neurotransmitter analysis and contribute to the development of next-generation diagnostic and therapeutic approaches for neurological diseases.}, } @article {pmid40583130, year = {2025}, author = {Yang, M and Wang, Q and Kang, D and Wang, S and Jiang, Y and Wang, JZ and Ming, C and Liu, R and Gu, J and Wang, X}, title = {Cryptic Splicing of GAP43 mRNA is a Novel Hallmark of TDP-43-Associated ALS and AD.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {}, number = {}, pages = {e12054}, doi = {10.1002/advs.202412054}, pmid = {40583130}, issn = {2198-3844}, support = {82330041//National Natural Science Foundation of China/ ; 92049107//National Natural Science Foundation of China/ ; 32171258//National Natural Science Foundation of China/ ; 2022-72-18//Science and Technology Innovation Team project from Department of Science and Technology of Hubei Province/ ; //Co-lnnovation Center of Neuroregeneration, Nantong University/ ; }, abstract = {Cytoplasmic aggregation of transactive response DNA-binding protein 43 (TDP-43) is a hallmark of amyotrophic lateral sclerosis (ALS) and occurs in 57% of Alzheimer's disease (AD) cases. TDP-43 regulates RNA processing, including cryptic exon splicing. Here, we demonstrate that TDP-43 directly controls growth-associated protein (GAP43) expression by binding to its pre-mRNA. Loss or hyperphosphorylation of TDP-43 disrupts this binding, leading to the inclusion of cryptic exon 4a1, which introduces premature stop codons and reduces GAP43 protein levels. RNA sequencing analysis of ALS and AD brains revealed GAP43 downregulation, while 4a1 is upregulated in AD cases with phosphorylated TDP-43. TDP-43 knockdown impaired axonal regeneration in induced pluripotent stem cell (iPSC)-derived motor neurons, whereas GAP43 restoration rescued this defect. These findings suggest that the loss of GAP43 contributes to neurodegeneration in ALS and AD. The inclusion of GAP43 cryptic exon 4a1 may serve as a hallmark of TDP-43 proteinopathies, highlighting a mechanistic link between TDP-43 dysfunction and neuronal vulnerability.}, } @article {pmid40582511, year = {2025}, author = {Wei, JH and Hirsch, Y and Lehrer, LW and Hoyer, S}, title = {Response to Gordon et al's "Part 2: Management of intraoperative and perioperative bleeding".}, journal = {Journal of the American Academy of Dermatology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jaad.2025.05.1458}, pmid = {40582511}, issn = {1097-6787}, } @article {pmid40581791, year = {2025}, author = {Al Ojaimi, Y and Osman, S and Alarcan, H and Emond, P and Veyrat-Durebex, C and Lanznaster, D and Meme, S and Clemencon, R and Galineau, L and Corcia, P and Andres, C and Vourc'h, P and Masse, F and Trovero, F and Blasco, H}, title = {Identification of disease-associated molecular signatures in the Prp-TDP-43A315T mouse model of ALS: Toward preclinical biomarker development.}, journal = {Journal of neuropathology and experimental neurology}, volume = {}, number = {}, pages = {}, doi = {10.1093/jnen/nlaf071}, pmid = {40581791}, issn = {1554-6578}, support = {//Région Centre Val de Loire/ ; //French National Research Agency/ ; //ARSLA/ ; }, abstract = {Identifying disease-related molecular signatures that can be used as biomarkers is critical for the development of preclinical therapies for amyotrophic lateral sclerosis (ALS). In this study, we focused on the Prp-TDP-43A315T transgenic mouse model of ALS to explore peripheral and central molecular alterations associated with disease progression. Prp-TDP-43A315T transgenic (Tg) and C57BL/6J wild-type mice were monitored from 50 to 400 postnatal days. One cohort assessed phenotypic parameters and MRI activity at 3 timepoints, ie, before (T0), at disease onset (T1), and at end-stage (T2). A second cohort validated findings from the first using omics analyses of tissues to examine ALS-related markers. Tg mice showed reduced body weight, decreased grip strength and tail position, and increased gait impairment at T1. Changes in (p)TDP-43, NRF2, GFAP, and pAMPK expression were noted in brain samples from the second cohort at T1. Metabolomic and lipidomic analyses revealed shifts in specific molecules in the brain and muscle of Tg mice. These data highlight individual differences in ALS pathology and adaptive responses to TDP-43-induced damage. This model provides valuable insights into TDP-43 proteinopathies and presents an innovative method for analyzing pathophysiological pathways through dried blood spot analysis, thereby expanding its applicability across various research fields.}, } @article {pmid40581671, year = {2025}, author = {Ono, S and Nakamura, M and Ikegami, T and Kajiyama, Y and Kume, K and Takahashi, Y and Takahashi, M and Mochizuki, H and Mizusawa, H and Kawakami, H and Yakushiji, Y}, title = {Spinocerebellar ataxia type 2 followed by amyotrophic lateral sclerosis due to a pure CAG repeat expansion in ATXN2: a case report and literature review.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {}, number = {}, pages = {}, pmid = {40581671}, issn = {1590-3478}, abstract = {BACKGROUND: Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominant cerebellar ataxia caused by abnormal CAG expansions (≥ 34 repeats) in the ATXN2 gene (ATXN2), whereas intermediate CAG expansions (27-33 repeats) have been linked to amyotrophic lateral sclerosis (ALS).

CASE DESCRIPTION: A 53-year-old woman with longstanding cerebellar ataxia developed progressive upper limb weakness and muscle atrophy at the age of 51 years. On neurological examination, she was found to have ataxic dysarthria, slow saccadic eye movements, tongue atrophy with fasciculations, muscle atrophy and weakness in both upper limbs, hyperreflexia with Babinski's sign, and limb and gait ataxia. Brain magnetic resonance imaging (MRI) showed brainstem and cerebellar atrophy. Genetic analysis identified an expanded CAG-repeat of 39/22 in ATXN2, and screening for other known ALS-related gene mutations was negative, leading to a diagnosis of both SCA2 and ALS associated with ATXN2.

CONCLUSIONS: SCA2 is typically associated with uninterrupted CAG-repeat expansions, whereas ALS-related ATXN2 expansions usually contain at least one CAA triplet. However, despite carrying an uninterrupted CAG-repeat expansion, this patient developed ALS. This case shows that ALS can emerge several decades after SCA2 onset, even in patients with pure CAG-repeats, underscoring the need for long-term monitoring in SCA2 patients. Further research is needed to clarify the roles of repeat length, CAA interruptions, and other factors in ATXN2-related ALS.}, } @article {pmid40581653, year = {2025}, author = {Lin, LT and Shenouda, M and McGoldrick, P and Lau, A and Robertson, J}, title = {C9orf72 deficiency impairs the autophagic response to aggregated TDP-25 and exacerbates TDP-25-mediated neurodegeneration in vivo.}, journal = {Acta neuropathologica communications}, volume = {13}, number = {1}, pages = {136}, pmid = {40581653}, issn = {2051-5960}, support = {#189242, #507996, #20012625//ALS Society of Canada/ ; 2023-001//Association for Frontotemporal Degeneration/ ; MOP-137005//CIHR/Canada ; AL161011//Weston Brain Institute/ ; }, mesh = {Animals ; *C9orf72 Protein/deficiency/genetics ; *Autophagy/physiology/genetics ; *DNA-Binding Proteins/metabolism/genetics ; Mice ; Humans ; Amyotrophic Lateral Sclerosis/pathology/genetics/metabolism ; Mice, Transgenic ; Frontotemporal Dementia/pathology/genetics/metabolism ; Disease Models, Animal ; Male ; Neurons/pathology/metabolism ; Brain/pathology/metabolism ; *Nerve Degeneration/pathology/metabolism ; }, abstract = {Cytoplasmic aggregates of the predominantly nuclear TAR DNA-binding protein 43 (TDP-43) are a pathological hallmark of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) cases caused by G4C2 hexanucleotide repeat expansions in C9orf72 (C9-ALS/FTD). While these repeat expansions are associated with both gain- and loss-of-function mechanisms, the contribution of C9orf72 loss of function to disease pathogenesis remains unclear. C9orf72 has been shown to regulate autophagy, and its deficiency has been shown to exacerbate phenotypes in gain-of-function G4C2 models, implicating impaired autophagic clearance in disease pathogenesis. Here, we directly test whether C9orf72 deficiency exacerbates TDP-43 pathology and neurodegeneration in vivo. Using AAV9-vectors to drive neuron-specific expression of pathologically relevant C-terminal species of TDP-43, TDP-35 and TDP-25, we established models of TDP-43 pathology that recapitulate key disease features, including cytoplasmic aggregates, motor and cognitive decline, and neuronal loss. TDP-25 expression in particular produced robust, abnormally phosphorylated, ubiquitinated and p62-labelled cytoplasmic aggregates, modelling TDP-43 pathology in disease. Loss of C9orf72 in TDP-25-expressing mice accelerated the onset of motor deficits, increased neurodegeneration, and impaired the autophagic response to TDP-25 expression. These findings reveal that C9orf72 deficiency disrupts autophagy and exacerbates TDP-25-mediated toxicity in vivo, supporting a contributory role for C9orf72 loss-of-function in driving neurodegeneration in C9-ALS/FTD.}, } @article {pmid40581642, year = {2025}, author = {Sanadgol, N and Samadi, M and Voelz, C and Khalseh, R and Amini, J and Beyer, C and Kipp, M and Clarner, T}, title = {Genomic ncRNAs regulating mitochondrial function in neurodegeneration: a neglected clue in the complex etiopathogenesis of multiple sclerosis.}, journal = {Cell & bioscience}, volume = {15}, number = {1}, pages = {93}, pmid = {40581642}, issn = {2045-3701}, abstract = {Multiple sclerosis (MS), the most prevalent myelinopathy with unclear etiology, involves mitochondrial dysfunction that critically contributes to oligodendrocyte damage and neurodegeneration. Recent interest has surged around the role of inflammatory non-coding RNAs (ncRNAs) in mitochondrial function, particularly in the context of neurodegenerative diseases (NDs), where neuroinflammation is a hallmark feature. This review highlights the collection and characterization of mitochondrial-related ncRNAs (MRncRNAs) that have been extensively studied in the context of NDs. Through a literature review, we identified 35 MRncRNAs (23 miRNAs, 8 LncRNAs, and 4 circRNAs) across Parkinson's disease (PD), Amyotrophic Lateral Sclerosis (ALS), Alzheimer's disease (AD), and Huntington's disease (HD). Notably, the inflammatory miRNAs miR-34a and miR-146a were commonly dysregulated in both PD and AD, while in HD, only a single miRNA, miR-196a, was identified. As expected, due to the mitochondrial nature of PD, the majority of MRncRNAs (9 miRNAs, 8 lncRNAs, and 3 circRNAs) were associated with this disorder. Further bioinformatic analysis of MRmiRNAs revealed that miR-124-5p, -146a-3p, and -15b-3p target mitochondrial genes more than others, and mRNA of pro-apoptotic protein BCL2L11 is the most targeted. Notably, the link between these MRncRNAs and mitochondrial function in MS remains unidentified. By evaluating upregulated MS-related ncRNAs in patients and comparing them with identified MRncRNAs, we found nine overlapping miRNAs (miR-15b, miR-21, miR-27b, miR-34a, miR-124, miR-137, miR-146a, miR-155, and miR-92a) as well as two shared lncRNAs, MALAT1 and HOTAIR (called MS/MRncRNAs). Further bioinformatic analysis of MS/MRmiRNAs revealed that the autophagy pathway is the most involved. Six of these miRNAs are significantly involved in MR diseases. Notably, miR-34a-5p showed a connection to oligodendrocyte mitochondria, while miR-15b targeted two MR hub genes, SDHC and BCL2. Moreover, several hub proteins (HIF1A, STAT3, MAPK1, GSK3B) targeted by these miRNAs are well-known regulators of inflammatory pathways and mitochondrial homeostasis: These findings highlight the critical roles of ncRNAs in mitochondrial dysfunction and neurodegeneration, emphasizing the urgent need for experimental studies on MRmiRNAs, particularly in the context of MS and other myelinopathies.}, } @article {pmid40581291, year = {2025}, author = {Ha, T and Ganesh, S and Narendran, K and Uduman, MS and Rajan, R and Sankaridurg, P and Nguyen, N and Tran, H}, title = {Comparison of axial length measurements of myopic eyes from ocular biometers versus axial length estimator.}, journal = {Journal of AAPOS : the official publication of the American Association for Pediatric Ophthalmology and Strabismus}, volume = {}, number = {}, pages = {104254}, doi = {10.1016/j.jaapos.2025.104254}, pmid = {40581291}, issn = {1528-3933}, abstract = {PURPOSE: To compare axial length (AL) estimates of myopic eyes obtained using an axial length estimator (ALE) and AL measurements made with the IOLMaster 700 in India and the Lenstar 900 in Vietnam.

METHODS: This multicenter retrospective cross-sectional study analyzed masked data of both eyes from myopic children (<18 years of age). Estimated AL was derived from mean keratometry and refraction values using ALE. Differences between actual and estimated ALs and their correlation were assessed using Bland-Altman plots and intraclass correlation coefficients (ICCs).

RESULTS: A total of 237 myopic children (474 eyes) aged 5-16 years were included: 90 Indian and 147 Vietnamese children. ALE estimates on average exceeded actual AL measurements, with mean differences of -0.26 mm (95% limits of agreement, -1.25 to 0.73 mm) for ALE formula, and -0.21 mm (95% limits of agreement, -1.14 to 0.71 mm) for ALE data input. ICCs showed strong agreement: 0.90 (95% CI, 0.83-0.93) for actual AL versus ALE data input and 0.89 (95% CI, 0.78-0.93) for actual AL versus ALE formula. Indian children had shorter actual AL than Vietnamese children (24.56 ± 0.90 vs 24.91 ± 0.86 mm [P < 0.001]) and exhibited slightly smaller differences between actual and estimated AL (-0.13 vs -0.27 mm for ALE data input; -0.17 vs -0.31 mm for ALE formula).

CONCLUSIONS: In our cohorts, ALE demonstrated strong agreement with IOLMaster 700 and Lenstar 900 AL measurements in myopic children. ALE may be a useful clinical tool for this population when direct measurements of AL are unavailable.}, } @article {pmid40580876, year = {2025}, author = {García-Toscano, L and Rodríguez-Cueto, C and Furiano, A and Hind, W and de Lago, E and Fernández-Ruiz, J}, title = {Preclinical evaluation of cannabidiolic acid as a neuroprotective agent in TDP-43 transgenic mice, an experimental model of amyotrophic lateral sclerosis.}, journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie}, volume = {189}, number = {}, pages = {118288}, doi = {10.1016/j.biopha.2025.118288}, pmid = {40580876}, issn = {1950-6007}, mesh = {Animals ; *Amyotrophic Lateral Sclerosis/drug therapy/pathology/genetics/physiopathology/metabolism ; *Neuroprotective Agents/pharmacology/therapeutic use ; Disease Models, Animal ; Male ; Mice, Transgenic ; Mice ; Motor Neurons/drug effects/pathology/metabolism ; Microglia/drug effects/metabolism/pathology ; Spinal Cord/drug effects/pathology/metabolism ; *Cannabinoids/pharmacology ; *DNA-Binding Proteins/genetics/metabolism ; Dose-Response Relationship, Drug ; Motor Activity/drug effects ; Riluzole/pharmacology ; }, abstract = {Plant-derived cannabinoids, including Δ[9]-THC, cannabinol, and Sativex-like combinations, have shown neuroprotection in preclinical ALS models. However, minor phytocannabinoids like cannabidiolic acid (CBDA) remain unexplored. This study evaluated the neuroprotective effects of CBDA, cannabidivarin, CBD, Δ[9]-THC, and Δ[9]-tetrahydrocannabidivarin in Prp-hTDP-43(A315T) transgenic male mice from early symptomatic (day 65) to advanced stages (day 90). CBDA proved the most effective, improving motor coordination (rotarod test) and reducing neuronal cell death, gliosis, microglial reactivity, and pro-inflammatory mediators in the spinal cord. A dose-response study confirmed that 10 mg/kg CBDA improved motor performance and preserved motor neurons, while lower doses were less effective and higher doses caused toxicity. Flow cytometry revealed a shift from an M1 proinflammatory to an M2 anti-inflammatory phenotype in microglial cells after CBDA treatment, mirroring effects in BV2 cells exposed to LPS. Comparing CBDA with riluzole (standard ALS therapy), CBDA showed superior neuroprotection, except for rotarod performance, where no improvement was observed. A combination of CBD and riluzole failed to enhance efficacy and even weakened microglial response benefits. In conclusion, CBDA was the most effective of the five phytocannabinoids studied and outperformed riluzole in ALS models. These findings support further clinical evaluation of CBDA for ALS treatment.}, } @article {pmid40580685, year = {2025}, author = {Deng, Z and Chen, H and Chen, J and Du, Z and Zhou, W and Yuan, Z}, title = {Multifaceted roles of extracellular vesicles in the interplay of neuroinflammation and neurodegenerative diseases.}, journal = {Biochimica et biophysica acta. Molecular basis of disease}, volume = {1871}, number = {7}, pages = {167960}, doi = {10.1016/j.bbadis.2025.167960}, pmid = {40580685}, issn = {1879-260X}, mesh = {Humans ; *Extracellular Vesicles/metabolism/pathology ; *Neurodegenerative Diseases/pathology/metabolism ; Animals ; *Neuroinflammatory Diseases/pathology/metabolism ; Blood-Brain Barrier/metabolism/pathology ; Biomarkers/metabolism ; Cell Communication ; }, abstract = {Despite advances in understanding neurodegenerative disease mechanisms, effective treatments remain elusive. Extracellular vesicles (EVs), key mediators of intercellular communication within the central nervous system (CNS), are increasingly recognized for their involvement in the pathogenesis of neurodegenerative disorders like Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS) and Huntington's disease (HD). In vivo studies demonstrate EVs' crucial role in maintaining CNS homeostasis, modulating neuroinflammatory responses, and influencing tissue repair and regeneration following injury, thereby impacting disease progression and recovery. Their unique properties, including small size and ability to cross the blood-brain barrier (BBB), position them as promising candidates for both biomarkers and therapeutics in CNS diseases. This review delves into the significant impact of neuroinflammation on neurodegenerative conditions, specifically focusing on the multifaceted contributions of EVs and their intricate interplay with the inflammatory landscape. We explore EV biogenesis, cargo composition, diverse roles in neuroinflammation (including intercellular communication and neuroprotection), their potential as biomarkers and drug delivery vehicles across the BBB for diagnosis or treatment of neuroinflammation implemented neurodegenerative diseases.}, } @article {pmid40580336, year = {2025}, author = {Wang, T and Wang, Y and Yang, Y and Wang, S and Wang, X and Feng, H}, title = {Fisetin Attenuates Mutant SOD1 Aggregation in Amyotrophic Lateral Sclerosis via Nrf2-Mediated Autophagy Activation.}, journal = {Journal of molecular neuroscience : MN}, volume = {75}, number = {3}, pages = {84}, pmid = {40580336}, issn = {1559-1166}, support = {2020B11//the First Affiliated Hospital of Harbin Medical University Research Innovation Fund/ ; 2020B11//the First Affiliated Hospital of Harbin Medical University Research Innovation Fund/ ; 2020-127//the Health Commission Scientific Research Foundation of Heilongjiang Province of China/ ; 21042240013//2024 Heilongjiang Province Postdoctoral Research Start-up Fund/ ; }, mesh = {*NF-E2-Related Factor 2/metabolism/genetics ; *Autophagy ; Flavonols ; *Flavonoids/pharmacology ; *Amyotrophic Lateral Sclerosis/metabolism/drug therapy/genetics ; *Superoxide Dismutase-1/genetics/metabolism ; Mice ; Animals ; Motor Neurons/metabolism/drug effects ; Humans ; Cell Line ; Sequestosome-1 Protein/metabolism/genetics ; *Neuroprotective Agents/pharmacology ; Protein Aggregates ; Protein Aggregation, Pathological ; }, abstract = {Dysregulated autophagy and copper/zinc superoxide dismutase (SOD1) protein aggregation play a crucial role in amyotrophic lateral sclerosis (ALS). Here, we used stably transfected NSC34 motor neuron-like cells: (1) SOD1[G93A] mutants (G93A), (2) wild-type SOD1 (WT) controls, and (3) empty vector (EV) controls to observe the effects of fisetin. Pharmacological autophagy inhibition (Bafilomycin A1, 40 nM) and nuclear factor erythroid 2-related factor 2 (Nrf2) gene silencing (siRNA transfection) were employed to dissect molecular pathways. Protein aggregation dynamics and autophagy markers (LC3, p62/SQSTM1) were quantified through immunofluorescence and immunoblotting. SOD1[G93A] models exhibited impaired autophagic flux evidenced by elevated LC3-II and p62 levels, correlating with increased detergent-insoluble SOD1 aggregates. Fisetin treatment (1-10 μ M) dose-dependently reduced both soluble and aggregated SOD1[G93A] protein, concomitantly with restored autophagic flux. Mechanistically, fisetin promoted nuclear translocation while decreasing cytoplasmic Nrf2. After administration of an autophagy inhibitor and interference with Nrf2, the regulation of fisetin on p62 and mutant hSOD1 protein was inhibited. Our findings demonstrate that fisetin ameliorates mutant SOD1 proteotoxicity through coordinated activation of Nrf2-mediated autophagy pathways, suggesting therapeutic potential for SOD1-associated ALS pathologies.}, } @article {pmid40580315, year = {2025}, author = {Jellinger, KA}, title = {Co-occurrence of amyotrophic lateral sclerosis and multiple sclerosis: a rare but interesting association.}, journal = {Journal of neural transmission (Vienna, Austria : 1996)}, volume = {}, number = {}, pages = {}, pmid = {40580315}, issn = {1435-1463}, support = {Society for the Promotion of Research in Experimental Neurology, Vienna, Austria//Society for the Promotion of Research in Experimental Neurology, Vienna, Austria/ ; }, abstract = {Multiple sclerosis (MS) is an inflammatory demyelinating disease with highly variable clinical course and usual onset in younger age, caused by genetic and environmental factors. Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder that affects motor neurons in the brain and spinal cord, resulting in gradual loss of voluntary muscle and respiratory control. Both ALS and MS exhibit distinct underlying causes and disease mechanisms, despite some shared clinical effects. About 10% of ALS are linked to genetic factors, such as C9orf72, the remaining sporadic ones being potentially influenced by environmental, toxic and oxidative stress, while MS is an autoimmune disorder where the immune system leads to inflammation and attacks the myelin sheath, genetic predisposition and viral infections playing a role in its susceptibility. The co-occurrence of ALS and MS is extremely rare, with 46 cases being reported in the available literature from 1986 to 2024, while in the earlier literature, cases with coincidental muscular atrophy simulating ALS were described. In the overwhelming majority, ALS manifested between one and 41 years after the onset of MS; only in four cases was ALS present before detection of MS. The concurrence of MS and ALS can be explained by similarities in their pathogenesis related to neurodegeneration, inflammation, and/or genetic susceptibility. The role of rare genetic ALS forms in this comorbidity deserves further studies. The shared inflammatory component with a cascade of oxidative stress and other noxious mechanisms leads to progressive motor and bulbar or other symptoms that underscore the potential for cross-disease research to yield insights applicable to both conditions and their relations to immune-mediated disorders.}, } @article {pmid40580203, year = {2025}, author = {Pirozzi, MA and Canale, F and Di Nardo, F and Sharbafshaaer, M and Passaniti, C and Siciliano, M and Cirillo, M and Tessitore, A and Tedeschi, G and Esposito, F and Trojsi, F}, title = {Quantitative susceptibility mapping for investigating brain iron deposits in amyotrophic lateral sclerosis: correlations with clinical phenotype and disease progression.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {}, number = {}, pages = {1-9}, doi = {10.1080/21678421.2025.2522406}, pmid = {40580203}, issn = {2167-9223}, abstract = {Objective: Perturbation of iron homeostasis is a potential key mechanism involved in neurodegeneration across many neurological disorders, including amyotrophic lateral sclerosis (ALS). We hypothesized that changes in quantitative susceptibility mapping (QSM) could capture perturbations in brain iron concentration in subgroups of ALS patients stratified by clinical phenotype and disease progression. Method: We enrolled 38 ALS patients (23 males - mean age: 58.7 ± 9.8), screened by clinical (ALS functional rating scale-revised, ALSFRS-R) and neuropsychological scales. Patients were a posteriori classified as fast (n = 16) or slow (n = 22) progressors. Two subgroups were also considered: pyramidal (or upper motor neuron+, UMN+) patients (n = 18), and patients with other phenotypes (n = 20). Results: Comparing fast vs. slow progressors, significant differences in iron deposits were observed in the left (p = 0.028) and right amygdala (p = 0.022), and in susceptibility distribution on the right hippocampus (p = 0.0011). Comparing UMN+ vs. other phenotypes, significant susceptibility differences emerged in the left thalamus (p = 0.0014) and right amygdala (p = 0.001). QSM changes were associated with baseline ALSFRS-R (rho = 0.36, p = 0.026) in the left paracentral cortex, and iron concentration with UMN score (rho = 0.35, p = 0.034). Moreover, the Edinburgh Cognitive and Behavioral ALS Screen (ECAS) was associated with iron deposits in the left thalamus (rho=-0.46, p = 0.0041). Conclusions: We confirmed that QSM alterations in extra-motor areas and subcortical regions may be distinctive hallmarks of neurodegeneration in pure/dominant UMN phenotypes of ALS. Moreover, we showed that QSM could be a valuable tool to differentiate patients with different progression rates and phenotypes, suggesting that QSM may support a prognostically useful early stratification of ALS patients.}, } @article {pmid40580199, year = {2025}, author = {Allen, MD and Van Eijk, RPA and Knox, L and Carlton, J and Hobson, E and Mcdermott, CJ and Murray, D and Berry, J and Meyer, T and Genge, A}, title = {Variability across versions of the self-administered ALSFRS-R: a review and call for harmonization.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {}, number = {}, pages = {1-6}, doi = {10.1080/21678421.2025.2522400}, pmid = {40580199}, issn = {2167-9223}, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease predominantly affecting motor neurons resulting in substantial, progressive disability. The amyotrophic lateral sclerosis functional rating scale - revised (ALSFRS-R) is commonly used to assess and monitor functional status in patients with ALS. Additionally, it is the current regulatory accepted primary outcome measure documenting functional status in ALS clinical trials. The ALSFRS-R was originally designed to be administered to a patient by a trained professional. But over time it has been adapted to be performed independently by patients or their caregivers without assistance. Several different versions of the self-administered ALSFRS-R have been created over the past two decades, each with subtle but important differences. Some of these differences are related to language used in item wording or the platform for which the scale was intended to be administered (e.g. digitally). These differences across versions of the self-administered scale may be problematic as they could increase the heterogeneity of data collected across clinical trials or complicate interpretation of results across trials. Therefore, we highlight the need for a harmonized version of the self-administered ALSFRS-R to be used across all clinics and clinical trial sites internationally.}, } @article {pmid40578028, year = {2025}, author = {Yang, JL and Qian, SY and Chen, ML and Wang, LX and Wang, Y and Liu, JJ and Xi, CS and Yang, YX and Li, Y and Gao, C and Zheng, GQ}, title = {Skeletal muscle, neuromuscular organoids and assembloids: a scoping review.}, journal = {EBioMedicine}, volume = {118}, number = {}, pages = {105825}, pmid = {40578028}, issn = {2352-3964}, abstract = {Skeletal muscle organoids (SKMOs), neuromuscular organoids (NMOs), and assembloids have emerged as powerful in vitro models that simulate the intricate cellular interactions between muscle and nerve, offering a promising approach to study function, development, and disease at the neuromuscular junction (NMJ). Given the relevance of NMJ dysfunction in diseases such as amyotrophic lateral sclerosis (ALS), these models provide insights into disease modelling. Scoping reviews are particularly valuable when exploring broad or emerging areas, as they help identify key concepts and evolving methodologies. Here, we conducted a scoping review by searching five databases, ultimately including 17 studies focussing on the development and application of SKMOs, NMOs, and assembloids in muscle function modelling. We highlight recent advancements and summarise various differentiation protocols, primarily utilising the Wnt signalling pathway agonist CHIR99021 and basic fibroblast growth factor (bFGF) to induce pluripotent stem cells into 2D neuromesodermal progenitors, further differentiated into SKMOs, NMOs, and assembloids. We also reviewed their cellular compositions, including motor neurons, neural stem cells, terminal Schwann cells, and astrocytes, alongside related research outcomes. Additionally, we discuss key challenges such as iPSC donor selection, standardisation, vascularisation, and 3D organoid imaging. This scoping review provides a foundation for future research on muscle function modelling.}, } @article {pmid40577240, year = {2025}, author = {O'Brien, D and Alhathli, E and Harwood, C and Bhattacharya, D and Gupta, K and Julian, T and Weinreich, M and West, RJH and Wang, D and Byrne, RP and McLaughlin, RL and Wuu, J and Benatar, M and Cooper-Knock, J and Shaw, PJ}, title = {Extreme exercise in males is linked to mTOR signalling and onset of amyotrophic lateral sclerosis.}, journal = {Brain : a journal of neurology}, volume = {}, number = {}, pages = {}, doi = {10.1093/brain/awaf235}, pmid = {40577240}, issn = {1460-2156}, abstract = {Amyotrophic lateral sclerosis (ALS) is thought to be caused by interaction between genetic and environmental factors leading to motor neuron (MN) degeneration. Physical exercise has been linked to ALS but controversy remains. A key question is to determine which individuals might be at risk of exercise-associated ALS, because unnecessary avoidance of exercise could be harmful. We implemented complementary strategies including Mendelian randomization and multiple questionnaire-based measures of physical exercise in different cohorts. We include a prospective study in UK Biobank participants where we could test for a relationship between exercise and the timing of future ALS symptom onset. To interrogate the molecular basis of our observations we performed a genetic association study of 'extreme' exercise, equivalent to >6 hours of strenuous exercise or >12 hours of any leisure-time exercise per week. Our data suggest that the link between increased physical exercise and ALS is particularly important for males who perform the most activity; with no evidence of a link in females. We determined that extreme exercise in males is associated with loss-of-function genetic variants within a number of mammalian target of rapamycin (mTOR) signalling genes that are also differentially expressed in ALS spinal cord. Activity-induced mTOR signalling has been shown to selectively benefit MN. Therefore, our findings could imply that moderate exercise is neuroprotective via enhanced mTOR signalling, but extreme exercise in men is associated with neurotoxicity and ALS via a failure of this mechanism. There was no significant overlap between genes associated with extreme exercise and those associated with ALS risk, consistent with a true gene-environment interaction rather than a shared genetic basis. We are not yet able to make individual-level recommendations regarding exercise and risk of ALS, but our conclusions should focus future investigation.}, } @article {pmid40576748, year = {2025}, author = {Gupta, MK and Chauhan, K and Bhardwaj, S and Srivastava, R}, title = {Innovative Interventions: Postbiotics and Psychobiotics in Neurodegenerative Disease Treatment.}, journal = {Probiotics and antimicrobial proteins}, volume = {}, number = {}, pages = {}, pmid = {40576748}, issn = {1867-1314}, abstract = {Neurodegenerative disorders, including Huntington's disease, Amyotrophic lateral sclerosis, Alzheimer's disease, and Parkinson's disease, create more challenges as the population gets older and there are no curative therapies available. Recent advances in gut microbiome research have spotlighted postbiotics and psychobiotics as innovative therapeutic strategies targeting the gut-brain axis to alleviate neurodegenerative symptoms and slow disease progression. Postbiotics, which are metabolites and cellular components released by probiotic bacteria, and psychobiotics, a class of probiotics with potential mental health benefits, offer novel approaches to neuroprotection. This chapter examines the ways in which postbiotics and psychobiotics modulate inflammation, oxidative stress, neurotrophic factors, and gut barrier integrity to provide neuroprotective effects. We review scientific research that highlights the efficacy of specific microbial strains and their metabolites in enhancing cognitive function and reducing neurodegeneration. In addition, we explore the consequences of diet and specific nutrition on strengthening the therapeutic results of these medications. The purpose of this chapter is to provide a detailed analysis of the existing data supporting the use of postbiotics and psychobiotics in both the prevention and management of neurological diseases. By integrating perspectives from microbiology, neurology, and clinical nutrition, we highlight the potential of these interventions to enhance patient outcomes and quality of life. In addition, we discuss the translational limitations and future research approaches required to successfully transition these microbiome-based treatments from the laboratory to clinical practice, emphasizing the importance of a holistic and personalized approach in combating neurodegenerative diseases.}, } @article {pmid40576049, year = {2025}, author = {Rudnicki, SA and Gebrehiwet, P and Kupfer, S and Malik, FI and Meng, L and Simkins, T and Wei, J and Wolff, AA and Shefner, JM}, title = {Participant, site personnel and sponsor perspectives on decentralized trial features in COURAGE-ALS: a randomized clinical trial.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {}, number = {}, pages = {1-9}, doi = {10.1080/21678421.2025.2523941}, pmid = {40576049}, issn = {2167-9223}, abstract = {OBJECTIVES: To describe participant, site personnel (SP) and sponsor perspectives regarding their experiences with a decentralized clinical trial (DCT).

METHODS: COURAGE-ALS was a 48-week, double-blind, randomized, phase III, hybrid DCT of reldesemtiv versus placebo for ALS. Fifty participants completed semi-structured interviews at Week ∼22; the majority provided feedback on DCT features. Subsequently, a planned interim analysis led to termination of COURAGE-ALS for futility; 486 participants were randomized and dosed. SP completed an online survey focusing on operational aspects of the hybrid design.

RESULTS: RVs influenced the decision to pursue the trial in 13/31 participants. Remotely performing forced vital capacity (FVC) was a concern for 17/43 (40%). Survey response rate for SP was 41% (141/344). The trial was viewed as less time/labour for the site versus a traditional design by 52/136 (38%) of SP. Twenty percent (25/125) agreed their participants liked doing remote FVC assessments; 6% (7/109) of SP reported no challenges in obtaining FVC remotely. Technological problems were commonly reported by SP (71/109, 65%). Biospecimen collection and Revised Amyotrophic Lateral Sclerosis Functional Rating Scale done at in-clinic visits (ICVs) and return visits (RVs) had similar completion rates, FVCs were missed more often at RVs than ICVs (completion rates 82% vs. 96%, p < 0.001).

CONCLUSIONS AND RELEVANCE: Participants and SP viewed RVs favorably, despite common technical challenges. RV FVC assessments were more likely to be missed. COURAGE-ALS demonstrated that an interventional hybrid DCT is feasible in ALS but limitations remain that will need to be considered when designing future DCTs.

TRIAL REGISTRATION: ClinicalTrials.gov (NCT04944784).}, } @article {pmid40575896, year = {2025}, author = {Thorarinsson, BL and Halldorsdottir, KE and Hilmarsson, A and Sveinsson, OA}, title = {[Treatment of familial ALS with the drug tofersen].}, journal = {Laeknabladid}, volume = {111}, number = {7-08}, pages = {314-317}, doi = {10.17992/lbl.2025.0708.848}, pmid = {40575896}, issn = {1670-4959}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/drug therapy/diagnosis/cerebrospinal fluid ; Treatment Outcome ; Mutation ; Male ; Middle Aged ; Female ; Superoxide Dismutase-1/genetics ; Neurofilament Proteins/cerebrospinal fluid ; Injections, Spinal ; Iceland ; Genetic Predisposition to Disease ; *Oligonucleotides/administration & dosage/therapeutic use ; Adult ; Biomarkers/cerebrospinal fluid ; *Oligonucleotides, Antisense/administration & dosage ; Phenotype ; Hospitals, University ; Aged ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a severe and progressive neurodegenerative disorder. We describe four cases of familial ALS based on SOD1 mutations who received intrathecal treatment with the antisense oligonucleotide tofersen at Landspítali University Hospital Iceland. Since initiation of treatment, there has not been any significant deterioration, and three patients have shown signs of cinical improvement. The cerebrospinal fluid concentration of neurofilament light chain (Nf-L), a biomarker of neuronal axonal damage, has decreased to the reference range of healthy individuals. No serious side effects have been observed.}, } @article {pmid40575894, year = {2025}, author = {Eliasdottir, OJ}, title = {[Antisense oliconucleotides-potential treatment for familial Amyotrophic lateral sclerosis (ALS).].}, journal = {Laeknabladid}, volume = {111}, number = {7-08}, pages = {311}, doi = {10.17992/lbl.2025.0708.846}, pmid = {40575894}, issn = {1670-4959}, } @article {pmid40575640, year = {2025}, author = {Ahmed, S and Nashwan, AJ}, title = {Rising adult hepatitis A in Pakistan: Shifting trends and public health solutions.}, journal = {World journal of virology}, volume = {14}, number = {2}, pages = {102519}, pmid = {40575640}, issn = {2220-3249}, abstract = {This letter evaluates Shahid et al's study in 2025 on the rising hepatitis A virus (HAV) among adults in Pakistan, highlighting a shift in the virus's epidemiology. Once primarily a childhood disease in low-income regions, HAV is now increasingly affecting adults, also seen globally due to improved sanitation. The study highlights public health challenges from adult HAV infections, which can lead to complications like coagulopathy and acute liver failure. It also has limitations, including being a single-center study and lacking seroprevalence and socioeconomic data, indicating the need for further research. This letter calls for urgent public health measures to extend adult vaccination programs and improve sanitation to address the increasing HAV infection in adult populations.}, } @article {pmid40575450, year = {2025}, author = {Barker, MS and Shneider, NA and Manoochehri, M and Huey, ED and Lindenberger, EC}, title = {Excessive emotional reactivity in a case of behavioral variant frontotemporal dementia with amyotrophic lateral sclerosis.}, journal = {Psychiatry research case reports}, volume = {4}, number = {1}, pages = {}, pmid = {40575450}, issn = {2773-0212}, support = {R00 NS060766/NS/NINDS NIH HHS/United States ; R01 NS076837/NS/NINDS NIH HHS/United States ; }, abstract = {Although amyotrophic lateral sclerosis (ALS) is defined as a neuromuscular disease, cognitive and/or behavioral symptoms are relatively common, and a portion of ALS patients will meet criteria for behavioral variant frontotemporal dementia (bvFTD). In this report, we describe the case of a man with ALS with bvFTD (ALS-FTD) presenting with excessive emotional reactivity, including severe anger, aggression, and obsessive thoughts. We contrast this case with the decreased emotional reactivity that is usually observed in patients with bvFTD without ALS. We discuss possible explanations including that: 1) the behavioral symptoms of bvFTD and ALS-FTD are the same, but the motor dysfunction influences the clinical manifestations of the behavioral symptoms in ALS-FTD; 2) the emotional and behavioral symptoms of bvFTD and ALS-FTD are the same, but ALS-FTD patients come to clinical attention earlier in the course of their FTD than bvFTD patients without ALS; and 3) the emotional and behavioral symptoms of bvFTD and ALS-FTD could differ.}, } @article {pmid40574975, year = {2025}, author = {Lehto, A and Schumacher, J and Teipel, S and Machts, J and Vielhaber, S and Hermann, A and Prudlo, J and Kasper, E}, title = {Cerebellar grey matter volume is associated with semantic fluency performance in amyotrophic lateral sclerosis patients.}, journal = {Brain communications}, volume = {7}, number = {3}, pages = {fcaf230}, pmid = {40574975}, issn = {2632-1297}, abstract = {The cerebellum has been shown to contribute to different cognitive functions such as verbal fluency and different aspects of executive functioning, which are also commonly impaired in amyotrophic lateral sclerosis (ALS) patients. Whereas cerebellar involvement has been indicated in ALS patients in general, its relative contribution to the patients' specific cognitive deficits remains unclear. In the current analyses, the demographic, clinical, neuropsychological and imaging data of 120 ALS patients and 88 healthy controls were analysed. Grey matter volume (GMV) and white matter (WM) fractional anisotropy were extracted for a comprehensive list of cerebral and cerebellar regions and bootstrapped elastic net regularized regression analyses were employed to identify regional structural metrics that were related to various cognitive scores. We further examined the stability of predictor variables selection and the regression coefficient distributions across the bootstrap samples. Both regional GMV and WM integrity are featured as informative predictors for patients' cognitive scores. The GMV of cerebellar lobules V and VIIIa were related to semantic fluency, but cerebellar regions did not reliably contribute to other cognitive outcomes. The GMV of pallidum was positively correlated with fluency outcomes and working memory, whereas hippocampus volume was positively related to fluency and episodic memory outcomes. Unsurprisingly, educational achievement emerged as the most general and reliable predictor of cognitive performance. Based on the current findings, cerebellar GMV seems to be specifically associated with semantic fluency performance in ALS patients but not any of the other cognitive measures. Further cognitive functions were associated with both cerebral grey matter (GM) and WM metrics. Future investigations could examine the possible involvement of the cerebellum in the affective and social-emotional dysfunction present in a subset of ALS patients.}, } @article {pmid40574889, year = {2025}, author = {Kulshreshtha, NN and Barthélémy, P}, title = {Lock and key: locked G quadruplexes could be the key to new modalities in nucleic acid therapeutics.}, journal = {RSC medicinal chemistry}, volume = {}, number = {}, pages = {}, pmid = {40574889}, issn = {2632-8682}, abstract = {G quadruplexes are secondary structures formed by G-rich sequences in DNA/RNA. They are critical regulatory centres for gene activation and chromosome stability. Malfunctions in their number or topology often results in ailments such as frontotemporal dementia, amyotrophic lateral sclerosis, coronary heart disease, anaemia, and various cancers. Proteins and ligands can bind to them only if the quadruplex topology matches their requirements. Hence, stabilizing or destabilizing this topology can have profound implications in therapeutics. Novel nucleic acid modalities involving intra-conjugated G4s are an interesting prospect as they have a fixed topology without the use of additional ligand stabilizers. They could also efficiently bind to G4-associated proteins and have important consequences in clinical research and development. In this opinion, a justification for the development of these modalities is presented by highlighting their advantages and the potential applications that can be unlocked by locking G4 sequences.}, } @article {pmid40574761, year = {2025}, author = {Yıldız, GN and Çiftçi, B}, title = {Interplay between insomnia, anxiety, and depression.}, journal = {World journal of psychiatry}, volume = {15}, number = {6}, pages = {104796}, pmid = {40574761}, issn = {2220-3206}, abstract = {Insomnia, anxiety, and depression have become critical mental health issues exacerbated by the coronavirus disease 2019 pandemic, highlighting the importance of understanding their interrelationships. This article evaluates the study by Li et al, which investigates the links between insomnia, anxiety, and depression while examining the mediating role of cognitive failures and the moderating effect of neuroticism. The study employed a cross-sectional design with 1011 participants, using validated scales to measure insomnia severity, neuroticism, cognitive failures, and mental health indicators. Li et al found that approximately 40% of participants exhibited symptoms of anxiety, depression, and insomnia, with most cases being mild. The results demonstrated that cognitive failures play a mediating role in the relationship between insomnia and both anxiety and depression. Furthermore, neuroticism moderated the relationship between insomnia and cognitive failures, with a stronger effect observed in individuals with lower levels of neuroticism. These findings underscore the importance of considering personality traits and cognitive processes in understanding mental health outcomes. This study emphasizes the critical need for interventions aimed at reducing cognitive failures and enhancing emotional stability to mitigate the impact of insomnia on mental health. Strategies to improve sleep quality, boost cognitive resilience, and regulate emotional responses could significantly enhance individuals' mental well-being. Moreover, integrating personality assessments into mental health services could facilitate more effective and personalized interventions. This article provides an original perspective on the effects of the coronavirus disease 2019 pandemic on global mental health. The content of the article addresses the complex relationships between sleep disorders, cognitive function losses, and neuroticism in light of data compiled from existing literature and current research. In addition, how these relationships have deepened during the pandemic and the effectiveness of proposed treatment methods for these phenomena are discussed in comparison with previous studies. The arguments in the article offer new perspectives and suggestions aimed at filling gaps in the literature, and make an important contribution to both clinical practice and public health policies. Li et al's study provides a comprehensive framework for understanding the connections between insomnia, cognitive failures, and neuroticism, as well as their influence on anxiety and depression. The findings offer valuable implications for public health strategies, emphasizing the necessity of holistic approaches to address post-pandemic mental health challenges.}, } @article {pmid40574759, year = {2025}, author = {Kalawatia, M and Lucke-Wold, B and Mehrunkar, A}, title = {Closer look at the cardiovascular and metabolic predictors of postpartum depression.}, journal = {World journal of psychiatry}, volume = {15}, number = {6}, pages = {106283}, pmid = {40574759}, issn = {2220-3206}, abstract = {Postpartum depression (PPD) is a severe mental health disorder affecting 10% to 15% of postpartum women worldwide. Pre-eclampsia is a hypertensive disorder of pregnancy that has been identified as a significant factor for PPD due to its vascular dysfunction, systemic inflammation and neurobiological alterations. The neuroinflammatory mechanisms common to both pre-eclampsia and PPD, that contribute to depressive symptoms include elevated proinflammatory cytokines (interleukin-6, tumor necrosis factor-alpha), activation of the kynurenine pathway, and oxidative stress. To critically evaluate Wu et al's study, which investigates blood pressure variability (BPV) and gestational body mass index (BMI) as independent predictors of PPD. To integrate recent findings on the metabolic and cardiovascular links between depression, pre-eclampsia, and postpartum mental health outcomes. Pre-pregnancy BMI is found to be a stronger predictor of PPD than gestational weight gain. A vascular-neuropsychiatric connection has been indicated in pre-eclamptic women, indicating a significant correlation between BPV and depressive postpartum symptoms. There is increased susceptibility to depression due to neuroinflammation contributed by blood pressure fluctuations and metabolic dysregulation. The incidence of PPD could be reduced by early identification and intervention for BP fluctuations. Early detection and intervention in high-risk pregnancies should be conducted through public health strategies that prioritize awareness, education, and accessibility to mental health care.}, } @article {pmid40571936, year = {2025}, author = {Evans, DM and Smith, GD and Moen, GH}, title = {Woolf et al's "GWAS by subtraction" is not useful for cross-generational Mendelian randomization studies.}, journal = {BMC research notes}, volume = {18}, number = {1}, pages = {247}, pmid = {40571936}, issn = {1756-0500}, support = {2017942//National Health and Medical Research Council/ ; MC_UU_00011/1/MRC_/Medical Research Council/United Kingdom ; DE220101226//Australian Research Council/ ; 325640//Norges Forskningsråd/ ; }, abstract = {Mendelian randomization (MR) is an epidemiological method that can be used to strengthen causal inference regarding the relationship between a modifiable environmental exposure and a medically relevant trait and to estimate the magnitude of this relationship [1]. Recently, there has been considerable interest in using MR to examine potential causal relationships between parental phenotypes and outcomes amongst their offspring [–4] (interestingly one of the earliest exemplars of MR was confirmation that antenatal maternal folate was protective against offspring neural tube defects [1]). In a recent issue of BMC Research Notes, Woolf, Sallis, Munafo and Gill (2023) [5] (abbreviated as WSMG from now on) present a method they call “GWAS by subtraction” (not to be confused with GWAS by subtraction via genomic SEM [6, 7]), to derive genome-wide summary statistics for paternal smoking and other “paternal phenotypes” with the goal that these estimates can then be used in downstream (including two sample) MR studies [8]. Whilst a potentially useful goal, WSMG (2023) focus on the wrong parameter of interest for useful genome-wide association studies (GWAS) and downstream cross-generational MR studies, and the estimator that they derive is neither efficient nor appropriate for such use.}, } @article {pmid40571717, year = {2025}, author = {Khan, R and Rahman, N and Prasannan, A and Ganiyeva, K and Chakrabortty, S and Sangaraju, S}, title = {Phase transition and bandgap modulation in TiO2 nanostructures for enhanced visible-light activity and environmental applications.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {20309}, pmid = {40571717}, issn = {2045-2322}, abstract = {Due to its wide-ranging applications in the climate and energy fields, enhancing the visible-light photoactivity of TiO2 nanoparticles remains a crucial challenge in photocatalysis. Interestingly, this work examined the phase transition, structural, optical, and photocatalytic characteristics of TiO2 nanoparticles doped with Al[3][+]/Al[2][+] and S[6+] ions. It was observed that the anatase phase (AP) dominates in pure TiO2 (100%) nanoparticles, whereas the rutile phase (RP) content increases in doped samples, reaching 20 ± 2.1% for X1 (Al = 2%, S = 2%) and falling to 12 ± 1.2% in X4 (Al = 2%, S = 8%). The introduction of Al[3][+]/Al[2][+] and S[6+] induces oxygen vacancies (Ovs) and alters the phase stability, as evidenced by the reduction of transformation energy to - 0.033 eV, facilitating the AP to RP transition. The effective integration of dopants indicates that a redshift and intensity in the Photoluminescence spectrum reduced by X-series nanoparticles is due to band gap reductions (from 3.23 eV for pure TiO2 to 1.98 eV for X4) and distortions in the lattice generated by Al/S doping. Raman spectroscopy results show peak broadening and shifts due to lattice strain from dopants, which validates dopant incorporation via peak shifts in Fourier-transform infrared spectroscopy. ESR study reveals paramagnetic centers in Ti[3][+]-Ovs complexes, indicating defect-induced magnetic characteristics. When methylene blue (MB) dye is photocatalyzed under visible light exhibits increased activity and degradation efficiencies that are higher than pure TiO2. The pseudo-first-order kinetic results show that co-doping effectively improves photocatalytic activity. Rate constants of 0.017 min[-][1] for X4 are found to be much higher than 7.28 × 10[-][4] min[-][1] for pure TiO2 nanoparticles. Finally, anatase X-series samples degraded MB at a maximum rate of 96.4% in 150 min, outperforming undoped TiO2 (15%) and rutile-TiO2 nanoparticles (65% degradation). The fundamental mechanism explains that the photocatalytic characteristics of TiO2 are modulated by co-doping, which is why these compounds are potential candidates for environmental remediation applications.}, } @article {pmid40571609, year = {2025}, author = {Watanabe, Y and Uemoto, M and Otsuki, M and Fukuhara, H and Tajiri, Y and Murakami, T and Hanajima, R}, title = {Can language characteristics contribute to the classification of neurodegenerative disorders? -An exploratory study.}, journal = {Internal medicine (Tokyo, Japan)}, volume = {}, number = {}, pages = {}, doi = {10.2169/internalmedicine.5202-24}, pmid = {40571609}, issn = {1349-7235}, abstract = {Objective Evaluating language symptoms is challenging owing to their varied presentations. We developed a Japanese Language Screen (JLS) to assess 11 language aspects, including agrammatism, impairment of articulation and prosody (IAP), word recall, syntactic comprehension, meaning of proverbs, and writing, considering the unique features of the Japanese language. Methods Using the JLS, we assessed the language functions in patients with Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), progressive supranuclear palsy (PSP), and HC to identify language symptoms specific to each condition and determine whether the JLS can differentiate between diseases and HC. Results The study included 168 participants. The total JLS score categorized the participants' language status as normal or impaired. According to the total score, PSP patients had more severe language deficits than AD patients, despite comparable cognitive scores. Substantial differences were found in the 11 assessed items for each disease. Patients with AD and PSP showed decreased performance in more than half of the items compared to HC, with the PSP group being more impaired. ALS patients showed decreases in IAP and writing, notably in the meaning of proverbs, whereas PD was closely comparable to HC. Conclusion This study suggests that while the JLS is useful for understanding the language symptoms associated with neurodegenerative disorders, its ability to classify them remains limited.}, } @article {pmid40571082, year = {2025}, author = {Saucier, D and Bélanger, M and Liu, Z and Lavigne, E and O'Connell, C}, title = {Associations between long-term air pollution exposure and the development of amyotrophic lateral sclerosis: A matched case-control study.}, journal = {Environmental research}, volume = {284}, number = {}, pages = {122232}, doi = {10.1016/j.envres.2025.122232}, pmid = {40571082}, issn = {1096-0953}, abstract = {There is increasing evidence of an association between air pollution, particularly nitrogen dioxide (NO2), and the development of amyotrophic lateral sclerosis (ALS). However, investigation into sulfur dioxide (SO2) remains understudied. Also, empirical identification of confounding variables to adjust for in ALS environmental studies is largely absent. Thus, we created a multifactorial database, mapped hypothesized direct effects of air pollutants, and conducted a matched case-control study in New Brunswick, Canada to investigate the association between long-term exposure to various air pollutants and the development of ALS. Odds of ALS onset was significantly associated with increased SO2 exposure (OR = 1.23; 95 % CI: 1.02-1.47, per IQR increase of 0.14 ppb) in adjusted direct effect models, but not associated with exposure to NO2 (OR = 1.09; 95 % CI: 0.87-1.41, per IQR increase of 2.79 ppb), ozone (O3) (OR = 0.99; 95 % CI: 0.80-1.22, per IQR increase of 2.31 ppb), fine particulate matter (PM2.5) (OR = 0.99; 95 % CI: 0.80-1.23, per IQR increase of 0.52 μg/m[3]) or PM2.5(smoke) (OR = 1.05; 95 % CI: 0.83-1.35, per IQR increase of 0.68 μg/m[3]). As for recency models, SO2 remained significantly associated with ALS in both 5-year (OR = 1.21; 95 % CI: 1.03-1.43) and 10-year prior to onset sensitivity models (OR = 1.23; 95 % CI: 1.02-1.47). Our findings support the association between long-term exposure to air pollutants, particularly SO2, and the development of ALS, supporting the need for improved air pollution control measures.}, } @article {pmid40569529, year = {2025}, author = {Shin, M and Ha, T and Lee, S and Li, C and Choi, JH and Choi, JW}, title = {Biohybrid motor neuron spheroid composed of graphene/HUVEC/neural cell for 3D biosensing system to evaluate drug of amyotrophic lateral sclerosis.}, journal = {Nano convergence}, volume = {12}, number = {1}, pages = {29}, pmid = {40569529}, issn = {2196-5404}, support = {RS-2023-00259341//the National Research Foundation (NRF) of Korea funded by the Ministry of Science and ICT/ ; RS-2024-00344633//the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT)/ ; NRF-2022M3H4A1A01005271//the National R&D Program through the NRF funded by the Ministry of Science and ICT/ ; }, abstract = {A 3D motor neuron (MN) spheroid has been developed to investigate neurodegenerative and neuromuscular junction (NMJ) disease. However, core necrosis and reduced neurogenesis, impairing neural network formation, were observed as the MN spheroid matured. In this study, to enhance neural network formation, a biohybrid MN spheroid composed of neural cells/reduced graphene oxide (rGO)/human umbilical vein endothelial cells (HUVECs) was generated for the first time and applied to 3D biosensing system for MNJ disease. By incorporating rGO and HUVECs at the onset of human neural stem cell (hNSC) culture, rGO and HUVECs were evenly distributed within MN spheroid generated by differentiation of hNSC, which improved oxygen- and nutrient- supply by reduction of core necrosis, and enhanced neurogenesis. The fabricated biohybrid MN spheroid improved neural network formation and electrophysiological signal. This method was also applied to generate biohybrid cerebral organoids from human induced pluripotent stem cells (hiPSCs), emphasizing its versatility for diverse 3D neural models. Then, a 3D NMJ biosensing system was fabricated by positioning the biohybrid MN spheroid with muscle bundles to evaluate its utility in neuromuscular disease modeling. Biohybrid MN spheroids generated from induced pluripotent stem cells of sporadic amyotrophic lateral sclerosis (ALS) patients were used to make NMJ. Reduced contraction of the connected muscle bundle due to ALS could be restored by upon treatment with the bosutinib, ALS drug, demonstrating the potential use for drug screening. The method to generate biohybrid spheroid can be applied to generation of various biohybrid brain organoids, and the proposed 3D NMJ biosensing system can be used to drug screening of diverse neuromuscular diseases.}, } @article {pmid40569409, year = {2025}, author = {Thissen, J and Klassen, MD and Fischer, B and Hacker, MC and Breitkreutz, J and Teutenberg, T and Cunha, R}, title = {StreamFind: data processing workflows for qualification and quantification of biopharmaceutical drug products analyzed by size exclusion chromatography coupled to capillary-enhanced Raman spectroscopy.}, journal = {Analytical and bioanalytical chemistry}, volume = {417}, number = {19}, pages = {4469-4480}, pmid = {40569409}, issn = {1618-2650}, support = {16DKWN138//Bundesministerium für Bildung und Forschung/ ; KK5312603KA1//Bundesministerium für Wirtschaft und Klimaschutz/ ; }, mesh = {*Spectrum Analysis, Raman/methods ; *Chromatography, Gel/methods ; Principal Component Analysis ; *Software ; Workflow ; *Antibodies, Monoclonal/analysis ; *Biological Products/analysis ; Pharmaceutical Preparations/analysis ; Least-Squares Analysis ; }, abstract = {Innovative hyphenated technologies, such as size exclusion chromatography coupled with capillary-enhanced Raman spectroscopy (SEC-CERS), enable more comprehensive analyses of biopharmaceutical drug products. However, specialized software for processing and analyzing data from these advanced techniques is often lacking. This study introduces the R package StreamFind, which is designed to help users seamlessly process both chromatographic and Raman spectroscopic data within an integrated workflow. We detail the implementation and structure of StreamFind and demonstrate its ability in the in-depth analysis of biopharmaceutical products. The study shows its capability to differentiate monoclonal antibodies and entire biopharmaceutical formulations and to quantify various components based on their Raman spectra. Principal component analysis (PCA) identified significant differences among the biopharmaceutical products analyzed, while multivariate curve resolution-alternating least squares (MCR-ALS) proved to be an effective method for quantifying different components within these products. The StreamFind platform is designed to be extensible, to facilitate contributions from new users and to support the future integration of additional algorithms to process different types of complex analytical data.}, } @article {pmid40568280, year = {2025}, author = {Bouabdallaoui, A and Taouihar, S and Yahya, N and Adali, N and Nassik, H}, title = {Bulbar-Onset Amyotrophic Lateral Sclerosis Unmasked by General Anesthesia: A Case Report.}, journal = {Cureus}, volume = {17}, number = {5}, pages = {e84823}, pmid = {40568280}, issn = {2168-8184}, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that primarily affects the motor neurons in the brain and spinal cord, resulting in severe muscular weakness, atrophy, and loss of motor control. Patients with ALS are often highly sensitive to anesthetic drugs, specifically neuromuscular blocking agents, which can exacerbate muscle weakness and contribute to prolonged postoperative recovery times. In this article, we report a case of bulbar ALS diagnosed after postoperative extubation failure in a 51-year-old patient. Practitioners should consider this disease in cases of difficult postoperative ventilatory weaning and should be aware of the impact of surgery and anaesthesia on disease progression.}, } @article {pmid40568112, year = {2025}, author = {Calco, B and Sweeney, CL and Steiner, J and Wang, T and Markowitz, TE and Paul, S and Palicha, B and Dinges, S and Yoo, K and Henderson, L and McDonald, V and De Ravin, SS and Greenberg, B and Zerbe, CS and Notarangelo, LD and Holland, SM and Nath, A and Safavi, F}, title = {A novel frameshift mutation in Phosphoinositide 3-kinase regulatory subunit 1 (PIK3R1) causes immunodeficiency and Amyotrophic Lateral Sclerosis (ALS).}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2025.05.23.655625}, pmid = {40568112}, issn = {2692-8205}, abstract = {Mutations in PIK3R1 , a regulatory subunit of Class I PI3K, are implicated in immune disorders and neurological conditions. We identified a novel heterozygous pathogenic frameshift mutation (c.1710dup) in PIK3R1 in a patient with common variable immunodeficiency who developed slowly progressive Amyotrophic Lateral Sclerosis. Induced pluripotent stem cells (iPSCs) and iPSC-derived motor neurons (iMNs) demonstrated that this mutation resulted in PIK3R1 haploinsufficiency, with downstream activation of AKT, disruption of neuronal electrical function and increased apoptosis in iPSC-derived motor neurons. Single-cell RNA sequencing (scRNA-seq) and pathway analysis of differentially expressed genes showed apoptosis pathways were upregulated in neuronal clusters from iMNs harboring the PIK3R1 c.1710 dup mutation. Mutated iPSC-derived brain organoids were smaller than matched controls. scRNA-seq of brain organoids showed more active apoptosis in neuronal clusters of patient-derived brain organoids. These findings identify a critical and novel role for PIK3R1 haploinsufficiency in neuronal function and survival.}, } @article {pmid40568026, year = {2025}, author = {Peggion, C and Bonadio, RS and Stella, R and Scalabrin, S and Pasetto, L and Millino, C and Camporeale, L and Pacchioni, B and Bonetto, V and Bertoli, A and Cagnin, S and Massimino, ML}, title = {Restoration of myogenesis in ALS-myocytes through miR-26a-5p-mediated Smad4 inhibition and its impact on motor neuron development.}, journal = {Molecular therapy. Nucleic acids}, volume = {36}, number = {3}, pages = {102581}, pmid = {40568026}, issn = {2162-2531}, abstract = {Amyotrophic lateral sclerosis (ALS) is the most common adult-onset paralytic disorder, characterized primarily by a progressive loss of motor neurons (MNs) in which degeneration skeletal muscle involvement has been demonstrated. Skeletal muscle is a plastic tissue that responds to insults through proliferation and differentiation of satellite cells. Skeletal muscle degeneration and regeneration are finely regulated by signals that regulate satellite cell proliferation and differentiation. It is known that satellite cell differentiation is impaired in ALS, but little is known about the involvement of microRNAs (miRNAs) and their role in intercellular communication in ALS. Here we demonstrated impaired differentiation of satellite cells derived from ALS mice related to the impairment of myogenic p38MAPK and protein kinase A (PKA)/pCREB signaling pathways that can be regulated by miR-882 and -134-5p. These miRNAs participate in autocrine signaling in association with miR-26a-5p that, secreted from wild-type (WT) and captured by ALS myoblasts, enhances ALS-related myoblast differentiation by repressing Smad4-related signals. Moreover, miR-26a-5p and -431-5p work in a paracrine way ameliorating motoneuron differentiation. These findings emphasize the need to better understand intercellular communication and its role in ALS pathogenesis and progression. They also suggest that miRNAs could be targeted or used as therapeutic agents for myofiber and MN regeneration.}, } @article {pmid40566997, year = {2025}, author = {Wu, J and Yan, S and Bian, Y and Liu, R and Lyu, X and Zhang, Z and Huang, S and Chen, T and Cheng, L}, title = {The Impact of Splicing Dysregulation on Neuromuscular Disorders and Current Neuromuscular Genetic Therapies.}, journal = {Journal of neurochemistry}, volume = {169}, number = {6}, pages = {e70133}, doi = {10.1111/jnc.70133}, pmid = {40566997}, issn = {1471-4159}, support = {ZR2022QC052//Natural Science Foundation of Shandong Province/ ; 32200464//National Natural Science Foundation of China/ ; ZD2021036//Science and Technology Project of Hebei Education Department/ ; }, mesh = {Humans ; *Genetic Therapy/methods/trends ; *Neuromuscular Diseases/genetics/therapy ; Animals ; *RNA Splicing/genetics ; Alternative Splicing ; }, abstract = {Eukaryotic genes contain non-coding segments known as introns, which interrupt coding sequences. Consequently, eukaryotic transcription produces precursor messenger RNA (pre-mRNA) that relies on precise splicing to remove highly diverse introns from the genome and to generate the mature mRNA essential for maintaining normal cellular activities. The extensive heterogeneity of neurons necessitates complex splicing regulation, particularly alternative splicing, to ensure the accuracy of gene expression in neurogenesis, signal transduction, and synaptic function and to maintain stability and adaptability in the nervous system. With the improvement of genetic testing technology, aberrant splicing has been identified as a contributing factor to the pathogenesis of neuromuscular disorders (NMDs) such as spinal muscular atrophy (SMA), amyotrophic lateral sclerosis (ALS), Duchenne muscular dystrophy (DMD), myotonic dystrophy (DM), Charcot-Marie-Tooth disease (CMT), myasthenia gravis (MG), and multiple sclerosis (MS). Studying the correlation between splicing defects and neuromuscular disorders is crucial for gaining a more comprehensive understanding of the pathogenesis of these diseases and for developing effective therapies. In this review, we introduce the intricate process and key factors of pre-mRNA splicing, with a focus on aberrant splicing and pathogenesis in several major neuromuscular disorders, providing an overview of the latest therapeutic strategies.}, } @article {pmid40566837, year = {2025}, author = {Massey, C and Griffiths, AW and McDermott, C and Hobson, E}, title = {How healthcare professionals support cough and secretion management in amyotrophic lateral sclerosis (ALS): a UK national survey.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {}, number = {}, pages = {1-12}, doi = {10.1080/21678421.2025.2522401}, pmid = {40566837}, issn = {2167-9223}, abstract = {OBJECTIVE: To understand the practices of healthcare professionals supporting people with Amyotrophic Lateral Sclerosis (ALS) to manage cough and secretion issues. This includes utilization of and confidence in assessment and treatment techniques and barriers and enablers of care.

METHODS: An online cross-sectional survey was distributed to UK healthcare professionals involved in cough and/or secretion management care in people with ALS.

RESULTS: A total of 113 responses were analyzed, over half were from physiotherapists (52%). The majority (71%) of respondents reported a role managing saliva and secretions. Just under two thirds (60%) routinely assessed cough and almost all (89%) routinely assessed secretions. Healthcare professionals reported reduced confidence assessing secretions compared with cough and very few (5%) used validated secretion outcome measures. Participants reported lower confidence implementing all treatment strategies than recommending them. Multiple barriers to care were identified, including access to specialist care and equipment, education and skills training and a lack of evidence-based care guidelines.

CONCLUSION: Cough and secretion management is complex and involves numerous professional groups. There is a need for clinical and educational interventions that address knowledge and skill gaps in managing cough and secretion issues, which will help increase healthcare professionals' confidence in assessing and treating these complex problems.}, } @article {pmid40566744, year = {2025}, author = {Bai, J and Cheng, K and Zhang, N and Chen, Y and Ni, J and Wang, Z}, title = {Research advances in dysphagia animal models.}, journal = {Animal models and experimental medicine}, volume = {}, number = {}, pages = {}, doi = {10.1002/ame2.70054}, pmid = {40566744}, issn = {2576-2095}, support = {82172531//National Natural Science Foundation of China/ ; 2021Y9105//Joint Funds for the Innovation of Science and Technology, Fujian Province/ ; }, abstract = {Dysphagia is a common complication of stroke, Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). The construction of animal models of dysphagia is an important way to explore its pathogenesis and treatment. At present, the animal models of dysphagia mainly include rodents, nonhuman primates, and other mammals, such as pigs and dogs. This review systematically summarizes the establishment and evaluation of dysphagia animal models in stroke, PD, and ALS in three kinds of experimental animals, providing a basis for the selection of appropriate animal models of dysphagia.}, } @article {pmid40566588, year = {2025}, author = {Martinelli, I and Gianferrari, G and Santarelli, R and Zucchi, E and Simonini, C and Fini, N and Ghezzi, A and Gessani, A and Ferri, L and Smolik, K and Ferraro, D and Bedin, R and Gizzi, M and Sette, E and Vacchiano, V and Bonan, L and Zinno, L and De Massis, P and Canali, E and Medici, D and Terlizzi, E and Morresi, S and Santangelo, M and Patuelli, A and Currò Dossi, M and Longoni, M and Pugliatti, M and Filippini, T and Ferro, S and Errals Study Group, and Mandrioli, J}, title = {Exploring the Role of Diabetes in ALS: A Population-Based Cohort Study.}, journal = {Life (Basel, Switzerland)}, volume = {15}, number = {6}, pages = {}, pmid = {40566588}, issn = {2075-1729}, support = {GPG/2022/1343//The Emilia Romagna Registry for ALS (ERRALS) is supported by a grant from the Emilia Romagna Regional Health Authority/ ; }, abstract = {Type 2 diabetes mellitus (T2DM) as a comorbidity in amyotrophic lateral sclerosis (ALS) has sparked interest for its potential impact on disease expression and prognosis. In this retrospective cohort study, we investigated the prevalence and clinical correlates of T2DM in a large cohort of patients from the ALS registry of a Northern Italy region, Emilia Romagna, established in 2009. Out of 1756 ALS patients enrolled up to 2021, 145 were affected by T2DM (diALS). Patients with diALS were older than those without T2DM (ndALS) (71.56 vs. 65.76 years, p < 0.001), had a higher body mass index (25.63 vs. 24.23, p < 0.001), but experienced greater weight loss at diagnosis (6.87% vs. 5.44%, p < 0.007). Respiratory onset (6.2% vs. 2.6%, p = 0.013) and respiratory phenotype (4.2% vs. 1.4%, p = 0.04) were more frequent among diALS. Coherently, diALS presented a lower forced vital capacity (74.9% vs. 87.9%, p ≤ 0.001) and more frequently adopted Non-Invasive Ventilation (NIV) (50.35% vs. 37.61%, p = 0.003), with significant influence on time to NIV (HR 1.71, 95% CI 1.07-2.74, p = 0.024). Exploring genetic background, among all the genes examined C9ORF72 emerged as underrepresented among diALS (7.64% in ndALS vs. 0% in diALS, p = 0.039). In conclusion, we confirmed a more severe respiratory dysfunction in diALS, suggesting a specific frailty in respiratory muscles, together with some peculiar clinical features consistent with the previous literature data, such as a later onset. The lower prevalence of C9ORF72 expansion in this population may hint towards a specific role of the gene in metabolism and inflammation, granting more space to non-genetic causes, warranting further studies for confirmation.}, } @article {pmid40565582, year = {2025}, author = {Rother, F and Parmar, AR and Bodenhagen, JS and Marvaldi, L and Hartmann, E and Bader, M}, title = {Deficiency in KPNA4, but Not in KPNA3, Causes Attention Deficit/Hyperactivity Disorder like Symptoms in Mice.}, journal = {Genes}, volume = {16}, number = {6}, pages = {}, pmid = {40565582}, issn = {2073-4425}, support = {2021 Grant//Rita Levi Montalcini 2021 Grant (MIUR, Italy)/ ; MIUR project "Dipartimenti di Eccellenza 2023-2027"//Ministero dell'Istruzione dell'Università e della Ricerca/ ; }, mesh = {Animals ; *alpha Karyopherins/genetics/deficiency ; *Attention Deficit Disorder with Hyperactivity/genetics/pathology/metabolism ; Mice ; Mice, Knockout ; Disease Models, Animal ; Motor Neurons/metabolism/pathology ; Male ; }, abstract = {Nucleocytoplasmic transport is crucial for neuronal cell physiology and defects are involved in neurodegenerative diseases like amyotrophic lateral sclerosis and Alzheimer's disease, but also in ageing. Recent studies have suggested, that the classic nuclear import factor adapters KPNA3 (also named importin alpha4) and KPNA4 (also named importin alpha3) could be associated with the development of motor neuron diseases, a condition specifically affecting the neurons projecting from brain to spinal cord or from spinal cord to the muscles. Here we set out to analyze the neuronal function of mice deficient in KPNA3 (Kpna3-KO) or KPNA4 (Kpna4-KO). The motoric abilities and locomotion at different time points in ageing were tested to study the role of these two genes on motor neuron function. While we did not find deficits related to motor neurons in both mouse models, we discovered a hypermotoric phenotype in KPNA4-deficient mice. Attention deficit/hyperactivity disorder (ADHD) is caused by a combination of genetic, environmental and neurobiological factors and a number of genes have been suggested in genome-wide association studies to contribute to ADHD, including KPNA4. Here we provide supportive evidence for KPNA4 as a candidate pathogenic factor in ADHD, by analysing Kpna4-KO mice which show ADHD-like symptoms.}, } @article {pmid40565515, year = {2025}, author = {Falduti, A and Giovinazzo, A and Lo Feudo, E and Rocca, V and Brighina, F and Messina, A and Conforti, FL and Iuliano, R}, title = {The Role of Non-Coding RNAs in ALS.}, journal = {Genes}, volume = {16}, number = {6}, pages = {}, pmid = {40565515}, issn = {2073-4425}, support = {Project P20225J5NB//Project P20225J5NB "Identifying pathogenic pathways in sporadic Amyotrophic Lateral Sclerosis: a genetic, omics and functional study" PRIN PNRR/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/genetics/pathology ; Humans ; *RNA, Long Noncoding/genetics ; *MicroRNAs/genetics ; *RNA, Circular/genetics ; Motor Neurons/metabolism/pathology ; Animals ; *RNA, Untranslated/genetics ; Biomarkers/metabolism ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that affects motor neurons, leading to muscle weakness, paralysis, and eventually death. The pathogenesis of ALS is influenced by genetic factors, environmental factors, and age-related dysfunctions. These factors, taken together, are responsible for sporadic cases of ALS, which account for approximately 85-90% of ALS cases, while familial ALS accounts for the remaining 10-15% of cases, usually with dominant traits. Despite advances in understanding and studying the disease, the cause of the onset of ALS remains unknown. Emerging evidence suggests that non-coding RNAs, including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), play crucial roles in the pathogenesis of the disease. An abnormal expression of these molecules is implicated in various ALS-related processes, including motor neuron survival, protein aggregation, and inflammation. Here, we describe the dysregulation of non-coding RNAs in the pathogenic mechanism of ALS, highlighting the potential roles of miRNAs, lncRNAs, and circRNAs as biomarkers or therapeutic targets to examine the progression of the disease.}, } @article {pmid40565514, year = {2025}, author = {Roque-Ramírez, B and Ríos-López, KE and López-Hernández, LB}, title = {Decoding Neuromuscular Disorders: The Complex Role of Genetic and Epigenetic Regulators.}, journal = {Genes}, volume = {16}, number = {6}, pages = {}, pmid = {40565514}, issn = {2073-4425}, mesh = {Humans ; *Epigenesis, Genetic ; *Neuromuscular Diseases/genetics ; DNA Methylation/genetics ; Amyotrophic Lateral Sclerosis/genetics ; Animals ; }, abstract = {Neuromuscular disorders (NMDs), such as amyotrophic lateral sclerosis (ALS), spinal muscular atrophy (SMA), and muscular dystrophies (e.g., Duchenne muscular dystrophy, DMD), are primarily driven by genetic mutations but are critically modulated by epigenetic mechanisms such as DNA methylation, histone modifications, and noncoding RNA activity. These epigenetic processes contribute to phenotypic variability and disease progression, and emerging evidence suggests that environmental factors, particularly nutrition and exercise, may further influence the molecular pathways that modulate these diseases. Dietary bioactive compounds (e.g., polyphenols and omega-3 fatty acids) exhibit epigenetic modulatory properties, which could mitigate oxidative stress, inflammation, and muscle degeneration in NMDs. For example, the inhibition of DNMTs and HDACs by curcumin in ALS models and the promyogenic effects of green tea catechins in DMD suggest plausible, though still requiring investigation, therapeutic avenues. However, the clinical application of nutriepigenetic interventions is preliminary and requires further validation. This review examines the interaction of genetic and epigenetic factors in ALS, SMA, and muscular dystrophies, highlighting their combined role in the heterogeneity of these diseases. Integrative therapeutic strategies combining gene therapies, epigenetic modulators, and lifestyle interventions may offer a multidimensional approach to the management of NMD. A deeper understanding of these interactions will be essential for advancing precision medicine and improving patient outcomes.}, } @article {pmid40565135, year = {2025}, author = {Bono, N and Fruzzetti, F and Farinazzo, G and Candiani, G and Marcuzzo, S}, title = {Perspectives in Amyotrophic Lateral Sclerosis: Biomarkers, Omics, and Gene Therapy Informing Disease and Treatment.}, journal = {International journal of molecular sciences}, volume = {26}, number = {12}, pages = {}, pmid = {40565135}, issn = {1422-0067}, support = {//Italian Ministry of Health (RRC)/ ; T4-AN-09 prog. ZRPOS2//CALabria HUB per Ricerca Innovativa ed Avanzata- CALHUB.RIA "Creazione di Hub delle Sci-enze della Vita"/ ; ZRA124//AriSLA foundation, "Bulb-Omics"/ ; PNRR-MCNT2-2023-12377336//the European Union - Next Generation EU - NRRP M6C2 - Investment 2.1 Enhancement and strengthening of biomedical research in the NHS/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/therapy/genetics/diagnosis/metabolism ; Humans ; *Genetic Therapy/methods ; *Biomarkers/metabolism ; C9orf72 Protein/genetics ; Animals ; Gene Editing ; Superoxide Dismutase-1/genetics ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive loss of upper and lower motor neurons, leading to muscle weakness, paralysis, and ultimately respiratory failure. Despite advances in understanding its genetic basis, particularly mutations in Chromosome 9 Open Reading Frame 72 (C9orf72), superoxide dismutase 1 (SOD1), TAR DNA-binding protein (TARDBP), and Fused in Sarcoma (FUS) gene, current diagnostic methods result in delayed intervention, and available treatments offer only modest benefits. This review examines innovative approaches transforming ALS research and clinical management. We explore emerging biomarkers, including the fluid-based markers such as neurofilament light chain, exosomes, and microRNAs in biological fluids, alongside the non-fluid-based biomarkers, including neuroimaging and electrophysiological markers, for early diagnosis and patient stratification. The integration of multi-omics data reveals complex molecular mechanisms underlying ALS heterogeneity, potentially identifying novel therapeutic targets. We highlight current gene therapy strategies, including antisense oligonucleotides (ASOs), RNA interference (RNAi), and CRISPR/Cas9 gene editing systems, alongside advanced delivery methods for crossing the blood-brain barrier. By bridging molecular neuroscience with bioengineering, these technologies promise to revolutionize ALS diagnosis and treatment, advancing toward truly disease-modifying interventions for this previously intractable condition.}, } @article {pmid40564215, year = {2025}, author = {Yoo, JK and Kwon, SH and Yoon, SH and Lee, JE and Chun, JU and Chung, JH and Lee, SY and Lee, JH and Chae, YR}, title = {Multi-Metal Exposure Profiling in ALS Patients in South Korea via Hair Analysis: A Cross-Sectional Study.}, journal = {Biomedicines}, volume = {13}, number = {6}, pages = {}, pmid = {40564215}, issn = {2227-9059}, abstract = {OBJECTIVES: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease with an unclear etiology. This study aimed to assess chronic heavy metal exposure in ALS patients in South Korea by comparing hair concentrations of common (Hg, Pb, Cd) and rare (U, Th, Pt) metals with healthy controls.

METHODS: Hair samples were collected from 66 ALS patients and 70 healthy individuals at Rodem Hospital between 2022 and 2025. Metal concentrations were measured using inductively coupled plasma mass spectrometry (ICP-MS) following standardized washing and digestion protocols.

RESULTS: ALS patients showed significantly higher levels of Hg, Pb, Cd, Al, As, and U than controls (p < 0.05). Notably, 40% of ALS patients had Hg levels exceeding 50% of the reference upper limit, compared to only 10% of controls. Elevated levels of uranium and other rare metals were also observed in specific ALS cases.

CONCLUSIONS: These findings suggest a possible association between heavy metal exposure and ALS in South Korea. Hair analysis may serve as a useful tool for identifying environmental factors contributing to ALS pathogenesis.}, } @article {pmid40564128, year = {2025}, author = {Drewes, N and Fang, X and Gupta, N and Nie, D}, title = {Pharmacological and Pathological Implications of Sigma-1 Receptor in Neurodegenerative Diseases.}, journal = {Biomedicines}, volume = {13}, number = {6}, pages = {}, pmid = {40564128}, issn = {2227-9059}, abstract = {Originally identified as a potential receptor for opioids, the sigma-1 receptor is now recognized as an intracellular chaperone protein associated with mitochondria-associated membranes at the endoplasmic reticulum (ER). Over the past two decades, extensive research has revealed that the sigma-1 receptor regulates many cellular processes, such as calcium homeostasis, oxidative stress responses, protein folding, and mitochondrial function. The various functions of the sigma-1 receptor highlight its role as a central modulator of neuronal health and may be a promising pharmacological target across multiple neurodegenerative conditions. Herein, we provide an overview of the current pharmacological understanding of the sigma-1 receptor with an emphasis on the signaling mechanisms involved. We examine its pathological implications in common neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease, and multiple sclerosis. We then highlight how sigma-1 receptor modulation may influence disease progression as well as potential pharmacological mechanisms to alter disease outcomes. The translational potential of sigma-1 receptor therapies is discussed, as well as the most up-to-date results of ongoing clinical trials. This review aims to clarify the therapeutic potential of the sigma-1 receptor in neurodegeneration and guide future research in these diseases.}, } @article {pmid40563824, year = {2025}, author = {Hasan, A and Scuderi, SA and Capra, AP and Giosa, D and Bonomo, A and Ardizzone, A and Esposito, E}, title = {An Updated and Comprehensive Review Exploring the Gut-Brain Axis in Neurodegenerative Disorders and Neurotraumas: Implications for Therapeutic Strategies.}, journal = {Brain sciences}, volume = {15}, number = {6}, pages = {}, pmid = {40563824}, issn = {2076-3425}, abstract = {The gut-brain axis (GBA) refers to the biochemical bidirectional communication between the central nervous system (CNS) and the gastrointestinal tract, linking brain and gut functions. It comprises a complex network of interactions involving the endocrine, immune, autonomic, and enteric nervous systems. The balance of this bidirectional pathway depends on the composition of the gut microbiome and its metabolites. While the causes of neurodegenerative diseases (NDDs) vary, the gut microbiome plays a crucial role in their development and prognosis. NDDs are often associated with an inflammation-related gut microbiome. However, restoring balance to the gut microbiome and reducing inflammation may have therapeutic benefits. In particular, introducing short-chain fatty acid-producing bacteria, key metabolites that support gut homeostasis, can help counteract the inflammatory microbiome. This strong pathological link between the gut and NDDs underscores the gut-brain axis (GBA) as a promising target for therapeutic intervention. This review, by scrutinizing the more recent original research articles published in PubMed (MEDLINE) database, emphasizes the emerging notion that GBA is an equally important pathological marker for neurological movement disorders, particularly in Alzheimer's disease, Parkinson's disease, multiple sclerosis, amyotrophic lateral sclerosis, Huntington's disease and neurotraumatic disorders such as traumatic brain injury and spinal cord injury. Additionally, the GBA presents a promising therapeutic target for managing these diseases.}, } @article {pmid40563773, year = {2025}, author = {Swash, M and de Carvalho, M}, title = {Dynamics of Onset and Progression in Amyotrophic Lateral Sclerosis.}, journal = {Brain sciences}, volume = {15}, number = {6}, pages = {}, pmid = {40563773}, issn = {2076-3425}, abstract = {This review focuses on the complexities of amyotrophic lateral sclerosis (ALS) onset, highlighting the insidious nature of the disease and the challenges in defining its precise origin and early pathogenic mechanisms. The clinical presentation of ALS is characterised by progressive muscle weakness and wasting, often with widespread fasciculations, reflecting lower motor neuron hyperexcitability. The disease's pathogenesis involves a prolonged preclinical phase of neuronal proteinopathy, particularly TDP-43 accumulation, which eventually leads to motor neuron death and overt ALS. This review discusses the difficulties in detecting this transition and the implications for early therapeutic intervention. It also addresses the involvement of both the upper and lower motor neuron systems, as well as the importance of following presymptomatic patients with genetic mutations. The significance of understanding the distinct processes of TDP-43 deposition and subsequent neuronal degeneration in developing effective treatments is emphasised.}, } @article {pmid40563772, year = {2025}, author = {Artioli, G and Guardamagna, L and Succi, N and Guasconi, M and Diamanti, O and Dellafiore, F}, title = {Relational, Ethical, and Care Challenges in ALS: A Systematic Review and Qualitative Metasynthesis of Nurses' Perspectives.}, journal = {Brain sciences}, volume = {15}, number = {6}, pages = {}, pmid = {40563772}, issn = {2076-3425}, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that leads to severe functional decline and death, imposing significant physical, emotional, and ethical burdens on patients and healthcare providers. With no curative treatment, ALS care depends on the early and sustained integration of palliative care to address complex and evolving needs. Nurses play a pivotal role in this process, yet their lived experiences remain underexplored. This study aimed to synthesize qualitative evidence on nurses' experiences in ALS care, with a focus on emotional, ethical, and palliative dimensions.

METHODS: A meta-synthesis of qualitative studies was conducted using Sandelowski and Barroso's four-step method. A systematic search across five databases identified eight studies exploring nurses' experiences with ALS care. Thematic synthesis was applied to extract overarching patterns.

RESULTS: Three core themes emerged: (1) Relational Dimension: From challenges to empathy and Trust and mistrust-emphasizing communication barriers and the value of relational trust; (2) Care Dimension: Competence, Palliative care needs, and Rewarding complexity-highlighting the emotional demands of care, the need for timely palliative integration, and the professional meaning derived from ALS care; (3) Ethical Dimension: Medical interventionism and Patient-centered values-exploring dilemmas around life-sustaining treatments, patient autonomy, and end-of-life decisions.

CONCLUSION: Nurses in ALS care face complex emotional and ethical challenges that call for strong institutional support and palliative training. Enhancing palliative care integration from diagnosis, alongside targeted education and psychological support, is crucial to improving care quality and sustaining the well-being of both patients and nurses.}, } @article {pmid40563439, year = {2025}, author = {Marini, C and Riondato, M and Dighero, E and Democrito, A and Losacco, S and Emionite, L and Nobbio, L and Di Patrizi, I and Camera, M and Ghersi, C and Ghelardoni, M and Lanfranchi, F and Vitale, F and Carta, S and Chiesa, S and Torazza, C and Milanese, M and Bauckneht, M and Hamedani, M and Zaottini, F and Schenone, A and Martinoli, C and Grillo, F and Sambuceti, G}, title = {Increased [[18]F]DPA-714 Uptake in the Skeletal Muscle of SOD1[G93A] Mice: A New Potential of Translocator Protein 18 kDa Imaging in Amyotrophic Lateral Sclerosis.}, journal = {Biomolecules}, volume = {15}, number = {6}, pages = {}, pmid = {40563439}, issn = {2218-273X}, support = {RF-2018-12366238//Italian Ministry of Health/ ; }, mesh = {Animals ; *Amyotrophic Lateral Sclerosis/diagnostic imaging/metabolism/genetics/pathology ; Mice ; Mice, Transgenic ; *Muscle, Skeletal/metabolism/diagnostic imaging ; Positron-Emission Tomography/methods ; *Receptors, GABA/metabolism ; *Superoxide Dismutase-1/genetics/metabolism ; *Pyrimidines/pharmacokinetics ; *Pyrazoles/pharmacokinetics ; Fluorine Radioisotopes ; Disease Models, Animal ; Humans ; Tissue Distribution ; Brain/metabolism/diagnostic imaging ; Male ; }, abstract = {PURPOSE: The skeletal muscle has been proposed to contribute to the progressive loss of motor neurons typical of amyotrophic lateral sclerosis (ALS). However, this mechanism has not yet been clarified due to the lack of suitable imaging tools. Here, we aimed to verify whether PET imaging of the translocator protein 18 kDa (TSPO) can detect a muscular abnormality in an experimental model of ALS.

METHODS: In vivo biodistribution and kinetics of [[18]F]DPA-714 were analyzed in skeletal muscle and brain of SOD1[G93A] transgenic mice and in wildtype (WT) littermates. Both cohorts were divided into three groups (n = 6 each) to be studied at 60, 90 and 120 days. After microPET imaging, animals were sacrificed to evaluate inflammatory infiltrates by hematoxylin/eosin staining and TSPO expression by immunohistochemistry and Western blot in both quadriceps and brain.

RESULTS: [[18]F]DPA-714 uptake was higher in the skeletal muscles of SOD1[G93A] than in WT mice in the preclinical phase (60 and 90 days) and further increased up to the symptomatic late stage (120 days). Inflammatory cells were absent in the quadriceps of SOD1[G93A] mice whose myocytes, instead, showed a progressive increase in TSPO expression with advancing age. By contrast, brain tracer uptake and TSPO expression were comparably low in both groups, regardless of age and genotype.

CONCLUSION: Upregulation of TSPO expression is characteristic of skeletal muscle, but not the brain, in the experimental SOD1[G93A] mouse model of ALS. Tracers targeting this pathway have been mostly proposed for the evaluation of inflammatory processes within the central nervous system. Nevertheless, the ubiquitous nature of TSPO expression and its responsiveness to various signals may broaden the diagnostic potential of these tracers to include disease conditions beyond inflammation.}, } @article {pmid40563328, year = {2025}, author = {Chong, ZZ and Souayah, N}, title = {Oxidative Stress: Pathological Driver in Chronic Neurodegenerative Diseases.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {14}, number = {6}, pages = {}, pmid = {40563328}, issn = {2076-3921}, abstract = {Oxidative stress has become a common impetus of various diseases, including neurodegenerative diseases. This review introduces the generation of reactive oxygen species (ROSs) in the nervous system, the cellular oxidative damage, and the high sensitivity of the brain to ROSs. The literature review focuses on the roles of oxidative stress in neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS). Oxidative stress occurs when excessively produced free radicals are beyond the capability of endogenous antioxidants to scavenge, leading to the oxidation of proteins, lipids, and nucleic acids, stimulating neuroinflammatory responses, causing neuronal dysfunction, senescence, and death. The dysfunctional mitochondria and aberrant activities of metabolic enzymes are the major source of ROSs. The high vulnerability of the nervous system to ROSs underlies the critical roles of oxidative stress in neurodegenerative diseases. Gene mutations and other risk factors promote the generation of ROSs, which have been considered a crucial force causing the main pathological features of AD, PD, HD, and ALS. As a result, antioxidants hold therapeutic potential in these neurodegenerative diseases. The elucidation of the pathogenic mechanisms of oxidative stress will facilitate the development of antioxidants for the treatment of these diseases.}, } @article {pmid40563288, year = {2025}, author = {Dibwe, DF and Oba, S and Monde, S and Hui, SP}, title = {Inhibition of Triacylglycerol Accumulation and Oxidized Hydroperoxides in Hepatocytes by Allium cepa (Bulb).}, journal = {Antioxidants (Basel, Switzerland)}, volume = {14}, number = {6}, pages = {}, pmid = {40563288}, issn = {2076-3921}, abstract = {Recent studies have demonstrated that dietary plant extracts can inhibit the development of lipid droplets (LDs) and oxidized LDs (oxLDs) in hepatic cells. These findings suggest that such extracts may be beneficial in combating metabolic dysfunction-associated fatty liver disease (MAFLD) and its more advanced stage, metabolic dysfunction-associated steatohepatitis (MASH). We examined nine Allium extracts (ALs: AL1-9) to assess their capacity to decrease lipid droplet accumulation (LDA) and oxidative stress by suppressing lipid formation and oxidation in liver cells. Among the Allium extracts tested, AL6 exhibited significant inhibitory effects against LDA. Furthermore, we employed our lipidomic method to assess the accumulation and suppression of intracellular triacylglycerol (TAG) and oxidized TAG hydroperoxide [TG (OOH) n = 3] by AL6 in liver cells under oleic acid (OA) and linoleic acid (LA) loading conditions. These findings indicate that foods derived from Allium species prevent the formation of lipid droplets by decreasing intracellular lipids and lipid hydroperoxides in the hepatocytes. Analysis of the metabolome of bioactive lipid droplet accumulation inhibition (LDAI) AL6 using LC-MS/MS and 1D-NMR [[1]H, [13]C, DEPT 90, and 135] techniques revealed that AL6 is primarily composed of carbohydrates, glucosidic metabolites, and organosulfur compounds, with small amounts of polyols, fatty acyls, small peptides, and amino acids. This implies that AL6 could be a valuable resource for developing functional foods and drug discovery targeting metabolic dysfunction-associated fatty liver disease (MAFLD)/metabolic dysfunction-associated steatohepatitis (MASH) and related disorders.}, } @article {pmid40562771, year = {2025}, author = {Amado, DA and Robbins, AB and Whiteman, KR and Smith, AR and Chillon, G and Chen, Y and Fuller, JA and Patty, NA and Izda, A and Cheng, C and Nelson, S and Dichter, AI and Mazzoni, EO and Monteys, AM and Davidson, BL}, title = {AAV-based delivery of RNAi targeting ataxin-2 improves survival and pathology in TDP-43 mice.}, journal = {Nature communications}, volume = {16}, number = {1}, pages = {5334}, pmid = {40562771}, issn = {2041-1723}, support = {K08 NS114106/NS/NINDS NIH HHS/United States ; UH3 NS094355/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; *Amyotrophic Lateral Sclerosis/genetics/therapy/pathology/metabolism ; *Dependovirus/genetics ; Motor Neurons/metabolism/pathology ; Mice ; *Ataxin-2/genetics/metabolism ; *DNA-Binding Proteins/metabolism/genetics ; Humans ; *RNA Interference ; Genetic Vectors ; Disease Models, Animal ; Genetic Therapy/methods ; Male ; MicroRNAs/genetics ; Female ; }, abstract = {Amyotrophic lateral sclerosis (ALS) involves motor neuron death due to mislocalized TDP-43. Pathologic TDP-43 associates with stress granules (SGs), and lowering the SG-associated protein ataxin-2 (ATXN2) using Atxn2-targeting antisense oligonucleotides prolongs survival in TAR4/4 sporadic ALS mice but failed in clinical trials likely due to poor target engagement. Here we show that an AAV with potent motor neuron transduction delivering Atxn2-targeting miRNAs reduces Atxn2 throughout the central nervous system at doses 40x lower than published work. In TAR4/4 mice, miAtxn2 increased survival (50%) and strength, and reduced motor neuron death, inflammation, and phosphorylated TDP-43. TAR4/4 transcriptomic dysregulation recapitulated ALS gene signatures that were rescued by miAtxn2, identifying potential therapeutic mechanisms and biomarkers. In slow progressing hemizygous mice, miAtxn2 slowed disease progression, and in ALS patient-derived lower motor neurons, our AAV vector transduced >95% of cells and potently reduced ATXN2 at MOI 4 logs lower than previously reported. These data support AAV-RNAi targeting ATXN2 as a translatable therapy for sporadic ALS.}, } @article {pmid40562529, year = {2025}, author = {Ferese, R and Suppa, A and Campopiano, R and Scala, S and Sammarone, F and Di Pilla, L and Di Pardo, A and Chiaravalloti, MA and Griguoli, AM and Cannella, M and D'Alessio, C and Storto, M and Fanelli, M and Zampogna, A and Patera, M and Inghilleri, M and Ceccanti, M and Cambieri, C and Buttari, F and Peconi, C and Giardina, E and Zampatti, S and Centonze, D and Gambardella, S}, title = {New variants and genotype-phenotype correlation in KIF5A mutation: the contribution of a large Italian cohort.}, journal = {Journal of medical genetics}, volume = {}, number = {}, pages = {}, doi = {10.1136/jmg-2025-110801}, pmid = {40562529}, issn = {1468-6244}, abstract = {BACKGROUND: Variants in the Kinesin-family member 5A (KIF5A) gene are associated with a range of motor diseases, and a strong correlation between the protein domains (motor, stalk and tail) and the clinical phenotype has been proposed. However, several studies have reported exceptions contributing to a complex genotype-phenotype correlation in recent years. Further studies are needed to improve our knowledge about the prevalence of KIF5A variants and their genotype-phenotype correlation.

METHODS: 390 patients (220 hereditary spastic paraplegia, 80 Charcot-Marie-Tooth disease type 2 and 90 amyotrophic lateral sclerosis) have been selected for next-generation sequencing Clinical Exome.

RESULTS: Five patients have been found to carry causative variants in the KIF5A gene. Of these, three are familiar cases, and two are sporadic. Segregation analysis was performed on the familiar probands. The five patients with pathogenic variants represent 4% of the studied population, and the clinical and genetic analysis of these five families allowed us to examine different scenarios.Some of these data support the hypothesis of a complex correlation between domains and disease.

CONCLUSION: These data confirm the complex genotype-phenotype correlation, both in terms of clinical heterogeneity associated with a specific domain and variability within the members of the same family, but also suggest a strong genotype-phenotype correlation, both intrafamiliar and interfamiliar, produced by a few variants.}, } @article {pmid40562281, year = {2025}, author = {Sharma, J and Thakur, A and Rain, M and Khosla, R and Maity, K and Mathur, GR and Anand, A}, title = {Interplay between exercise and neuregulin in providing neuroprotection.}, journal = {Behavioural brain research}, volume = {493}, number = {}, pages = {115710}, doi = {10.1016/j.bbr.2025.115710}, pmid = {40562281}, issn = {1872-7549}, abstract = {Exercise has been shown to have a positive impact on brain health including neuroprotective function. It has been demonstrated to increase the synthesis of neurotrophic factors, support neuronal survival, and improve neuroplasticity. Concurrently, neuregulin plays a vital role in the development, maintenance, and repair of both the central and peripheral nervous system. The link between exercise and neuregulin in mediating neuroprotection has been the subject of increased research to better understand the possible applications for the deterrence of neurodegenerative disorders. Understanding this link is of great interest because it has the potential to lead to new strategies for preventing or slowing the progression of neurodegenerative diseases. With an emphasis on exercise-induced neuregulin-mediated neuroprotection, this article reviews the literature on the neuroprotective effects of exercise and neuregulin. The synergistic effects of exercise and neuregulin on neuroprotection will be clarified and valuable insights will be gained from this review, with potential implications for the development of novel therapeutic strategies for neurodegenerative diseases such as Amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), Alzheimer's disease (AD) and Huntington's disease (HD).}, } @article {pmid40562033, year = {2025}, author = {Lall, D and Workman, MJ and Sances, S and Ondatje, BN and Bell, S and Lawless, G and Woodbury, A and West, D and Meyer, A and Matlock, A and Vaibhav, V and Van Eyk, JE and Svendsen, CN}, title = {An organ-chip model of sporadic ALS using iPSC-derived spinal cord motor neurons and an integrated blood-brain-like barrier.}, journal = {Cell stem cell}, volume = {32}, number = {7}, pages = {1139-1153.e7}, pmid = {40562033}, issn = {1875-9777}, support = {UG3 NS105703/NS/NINDS NIH HHS/United States ; UG3 TR003264/TR/NCATS NIH HHS/United States ; UH3 NS105703/NS/NINDS NIH HHS/United States ; UH3 TR003264/TR/NCATS NIH HHS/United States ; }, mesh = {*Amyotrophic Lateral Sclerosis/pathology/metabolism/genetics ; Humans ; *Induced Pluripotent Stem Cells/metabolism/pathology/cytology ; *Motor Neurons/pathology/metabolism ; *Blood-Brain Barrier/pathology/metabolism ; *Spinal Cord/pathology ; *Lab-On-A-Chip Devices ; Cell Differentiation ; *Models, Biological ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder in which motor neurons (MNs) of the brain and spinal cord degenerate, leading to paralysis. Generating MNs from patient-specific induced pluripotent stem cells (iPSCs) may help elucidate early stages of disease. Here, we combined MNs from patients with early-onset disease with brain microvascular endothelial-like cells in a microfluidic device we termed spinal cord chips (SC-chips) and added media flow, which enhanced neuronal maturation and improved cellular health. Bulk transcriptomic and proteomic analyses of SC-chips revealed differences between control and ALS samples, including increased levels of neurofilaments. Single-nuclei RNA sequencing revealed the presence of two MN subpopulations and an ALS-specific dysregulation of glutamatergic and synaptic signaling. This ALS SC-chip model generates a diversity of mature MNs to better understand ALS pathology in a model that has an active blood-brain barrier-like system for future drug screening.}, } @article {pmid40560963, year = {2025}, author = {Pang, C and Li, Y and Jiang, W and Xie, H and Cao, W and Yu, H and Lin, Z and Cheng, Y and Fan, D and Deng, B}, title = {Analysis of retinal markers and incident amyotrophic lateral sclerosis: An optical coherence tomography-based cohort study.}, journal = {PLoS medicine}, volume = {22}, number = {6}, pages = {e1004545}, pmid = {40560963}, issn = {1549-1676}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/epidemiology/diagnostic imaging/diagnosis/pathology ; *Tomography, Optical Coherence ; Male ; Female ; Middle Aged ; *Retina/diagnostic imaging/pathology ; Biomarkers ; Aged ; Incidence ; Cohort Studies ; Adult ; United Kingdom/epidemiology ; Risk Factors ; }, abstract = {BACKGROUND: Biomarkers are widely recognized as crucial breakthroughs in tackling amyotrophic lateral sclerosis (ALS). Among them, retina markers may hold promise due to the close retina-brain connection and non-invasive, portable detection methods. Thus, using optical coherence tomography (OCT), we investigated the link between baseline cell-level retinal features and future ALS risk.

METHODS AND FINDINGS: Participants from the UK Biobank underwent OCT scans to assess retinal layers, macula, and optic disc parameters. Follow-up commenced two years after the baseline period (2006-2010), during which ALS cases were identified using International Classification of Diseases (ICD) codes from medical and assessment records. Cox proportional hazards models were applied to examine the relationship between retinal markers and incident ALS. Over a median follow-up of 14.11 years, 70 ALS cases occurred among 53,824 participants (incidence 10.58 per 100,000 person-years). Most participants were White (94.6%), 44.8% male, with a median age of 58 years. After adjusting for demographics and comorbidities affecting the retina, a standard deviation (SD) decrease of 15.19 µm in photoreceptor layer (PRL) thickness was associated with a 19% (95% confidence interval [7, 29]; p = 0.002) increased risk of ALS, while a SD increase of 26.11 µm in retinal pigment epithelium (RPE) thickness corresponded to a 20% (95% CI [7, 34]; p = 0.002) higher risk. Sensitivity analyses excluding follow-ups of less than 4 and 6 years yielded consistent results. Subgroup analyses showed these findings were more pronounced in smokers. The main limitation of this study is its single time point observational design.

CONCLUSION: A thinner PRL and thicker RPE may precede the clinical diagnosis of ALS, offering potential clues for early diagnosis and insights into the disease's pathogenesis.}, } @article {pmid40560475, year = {2025}, author = {Bamber, R and Stavroulakis, T and McDermott, C and Carlton, J}, title = {Health-related quality of life of informal carers in ALS: a systematic review of person reported outcome measures.}, journal = {Quality of life research : an international journal of quality of life aspects of treatment, care and rehabilitation}, volume = {}, number = {}, pages = {}, pmid = {40560475}, issn = {1573-2649}, support = {NIHR301648//National Institute for Health and Care Research/ ; }, abstract = {PURPOSE: Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative condition with swift progression. The devastating impact of ALS affects the health-related quality of life (HRQoL) of informal carers. Various person reported outcome measures (PROMs) have been used to assess HRQoL in informal carers in ALS, yet their validity remains unclear. This review aimed to identify and evaluate the content validity of HRQoL PROMs for informal carers in ALS.

METHODS: This review was conducted according to best practice COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) methodology. Two literature searches were conducted in November 2023 and April 2024 across MEDLINE, PsycINFO, Embase, CINAHL, the Cochrane Database of Systematic Reviews, CENTRAL and Google Scholar, to identify HRQoL PROMs used with informal carers in ALS, PROM development articles, and psychometric literature. Evidence synthesis followed COSMIN guidance.

RESULTS: 12,276 articles were screened, and 109 PROMs were identified, with 43 undergoing full COSMIN assessment. Content validity ratings were 'Inconsistent' or 'Insufficient' for all PROMs. All PROMs, except the CarerQoL, were rated 'Insufficient' for comprehensiveness. Only 18.6% of PROMs included informal carers in development. Quality of evidence supporting content validity ratings was 'Very Low' for 93% of PROMs.

CONCLUSION: HRQoL PROMs used with informal carers in ALS lack evidence to support their content validity, restricting their utility for this purpose. Existing literature on the impact of caring in ALS on informal carers' HRQoL should be interpreted cautiously. Further research is required to establish the content validity of HRQoL PROMs used for this cohort.}, } @article {pmid40560468, year = {2025}, author = {Sumra, V and Hadian, M and Dilliott, AA and Farhan, SMK and Frank, AR and Lang, AE and Roberts, AC and Troyer, A and Arnott, SR and Marras, C and Tang-Wai, DF and Finger, E and Rogaeva, E and Orange, JB and Ramirez, J and Zinman, L and Binns, M and Borrie, M and Freedman, M and Ozzoude, M and Bartha, R and Swartz, RH and Munoz, D and Masellis, M and Black, SE and Dixon, RA and Dowlatshahi, D and Grimes, D and Hassan, A and Hegele, RA and Kumar, S and Pasternak, S and Pollock, B and Rajji, T and Sahlas, D and Saposnik, G and Tartaglia, MC and , }, title = {Regional free-water diffusion is more strongly related to neuroinflammation than neurodegeneration.}, journal = {Journal of neurology}, volume = {272}, number = {7}, pages = {478}, pmid = {40560468}, issn = {1432-1459}, mesh = {Humans ; Male ; Aged ; Female ; *Neurodegenerative Diseases/diagnostic imaging/metabolism ; *Diffusion Magnetic Resonance Imaging/methods ; *Neuroinflammatory Diseases/diagnostic imaging/metabolism ; Middle Aged ; Neurofilament Proteins/blood ; Glial Fibrillary Acidic Protein/blood ; Biomarkers/blood ; Aged, 80 and over ; Cognitive Dysfunction/diagnostic imaging ; }, abstract = {INTRODUCTION: Recent research has suggested that neuroinflammation may be important in the pathogenesis of neurodegenerative diseases. Free-water diffusion (FWD) has been proposed as a non-invasive neuroimaging-based biomarker for neuroinflammation.

METHODS: Free-water maps were generated using diffusion MRI data in 367 patients from the Ontario Neurodegenerative Disease Research Initiative (108 Alzheimer's Disease/Mild Cognitive Impairment, 42 Frontotemporal Dementia, 37 Amyotrophic Lateral Sclerosis, 123 Parkinson's Disease, and 58 vascular disease-related Cognitive Impairment). The ability of FWD to predict neuroinflammation and neurodegeneration from biofluids was estimated using plasma glial fibrillary-associated protein (GFAP) and neurofilament light chain (NfL), respectively.

RESULTS: Recursive Feature Elimination (RFE) performed the strongest out of all feature selection algorithms used and revealed regional specificity for areas that are the most important features for predicting GFAP over NfL concentration. Deep learning models using selected features and demographic information revealed better prediction of GFAP over NfL.

DISCUSSION: Based on feature selection and deep learning methods, FWD was found to be more strongly related to GFAP concentration (measure of astrogliosis) over NfL (measure of neuro-axonal damage), across neurodegenerative disease groups, in terms of predictive performance. Non-invasive markers of neurodegeneration such as MRI structural imaging that can reveal neurodegeneration already exist, while non-invasive markers of neuroinflammation are not available. Our results support the use of FWD as a non-invasive neuroimaging-based biomarker for neuroinflammation.}, } @article {pmid40559965, year = {2025}, author = {Kim, WW and Zarus, G and Alman, B and Ruiz, P and Han, M and Mehta, P and Ji, C and Qureshi, H and Antonini, J and Shoeb, M}, title = {Metal-Induced Genotoxic Events: Possible Distinction Between Sporadic and Familial ALS.}, journal = {Toxics}, volume = {13}, number = {6}, pages = {}, pmid = {40559965}, issn = {2305-6304}, abstract = {Metal exposure is a potential risk factor for amyotrophic lateral sclerosis (ALS). Increasing evidence suggests that elevated levels of DNA damage are present in both familial (fALS) and sporadic (sALS) forms of ALS, characterized by the selective loss of motor neurons in the brain, brainstem, and spinal cord. However, identifying and differentiating initial biomarkers of DNA damage response (DDR) in both forms of ALS remains unclear. The toxicological profiles from the Agency for Toxic Substances and Disease Registry (ATSDR) and our previous studies have demonstrated the influence of metal exposure-induced genotoxicity and neurodegeneration. A comprehensive overview of the ATSDR's toxicological profiles and the available literature identified 15 metals (aluminum (Al), arsenic (As), cadmium (Cd), chromium (Cr), cobalt (Co), copper (Cu), iron (Fe), lead (Pb), manganese (Mn), mercury (Hg), nickel (Ni), selenium (Se), uranium (U), vanadium (V), and zinc (Zn)) showing exposure-induced genotoxicity indicators associated with ALS pathogenesis. Genetic factors including mutations seen in ALS types and with concomitant metal exposure were distinguished, showing that heavy metal exposure can exacerbate the downstream effect of existing genetic mutations in fALS and may contribute to motor neuron degeneration in sALS. Substantial evidence associates heavy metal exposure to genotoxic endpoints in both forms of ALS; however, a data gap has been observed for several of these endpoints. This review aims to (1) provide a comprehensive overview of metal exposure-induced genotoxicity in ALS patients and experimental models, and its potential role in disease risk, (2) summarize the evidence for DNA damage and associated biomarkers in ALS pathogenesis, (3) discuss possible mechanisms for metal exposure-induced genotoxic contributions to ALS pathogenesis, and (4) explore the potential distinction of genotoxic biomarkers in both forms of ALS. Our findings support the association between metal exposure and ALS, highlighting under or unexplored genotoxic endpoints, signaling key data gaps. Given the high prevalence of sALS and studies showing associations with environmental exposures, understanding the mechanisms and identifying early biomarkers is vital for developing preventative therapies and early interventions. Limitations include variability in exposure assessment and the complexity of gene-environment interactions. Studies focusing on longitudinal exposure assessments, mechanistic studies, and biomarker identification to inform preventative and therapeutic strategies for ALS is warranted.}, } @article {pmid40559225, year = {2025}, author = {Elgenidy, A and Hassan, IA and Hamed, Y and Hashem, HA and Abuel-Naga, O and Abdel-Rahman, HI and Mohamed, KR and Hamed, BM and Shehab, MA and Zeyada, M and Kassab, S and Abdelgawad, SSA and Ibrahim, AI and Hasanin, EH and Elhoufey, AA and Mahmoud, KH and Saad, K}, title = {Sonographic Evaluation of Peripheral Nerves and Cervical Nerve Roots in Amyotrophic Lateral Sclerosis: A Systematic Review and Meta-Analysis.}, journal = {Medical sciences (Basel, Switzerland)}, volume = {13}, number = {2}, pages = {}, pmid = {40559225}, issn = {2076-3271}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnostic imaging/pathology ; Ultrasonography/methods ; *Peripheral Nerves/diagnostic imaging/pathology ; *Spinal Nerve Roots/diagnostic imaging/pathology ; Middle Aged ; }, abstract = {BACKGROUND: Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease that leads to nerve atrophy. Ultrasonography has a significant role in the diagnosis of ALS.

AIM: We aimed to sonographically assess the size of all peripheral nerves and cervical nerve roots in ALS compared to controls.

METHODS: We searched MEDLINE (PubMed), Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL), Embase, and Scopus using comprehensive MeSH terms for the keywords nerve, ultrasound, and ALS. We extracted data regarding cross-sectional area (CSA) or diameter for the following nerves: vagus, phrenic, tibial, fibular, sural, radial, ulnar, and median nerves, and the roots of C5, C6, C7, and C8 in both ALS patients and controls.

RESULTS: Our study included 2683 participants, of which 1631 were ALS patients (mean age = 60.36), 792 were healthy controls (mean age = 57.79), and 260 were patients with other neurological disorders. ALS patients had significantly smaller nerve size compared to controls. Nerve size differences were observed in the vagus nerve [MD = -0.23], phrenic nerve [MD = -0.25], C5 nerve root [SMD = -0.94], C6 nerve root [SMD = -1.56], C7 nerve root [SMD = -1.18], C8 nerve root [MD = -1.9], accessory nerve [MD = -0.32], sciatic nerve [MD = -11], tibial nerve [MD = -0.68], sural nerve [MD = -0.32,], ulnar nerve [MD = -0.80], and median nerve [MD = -1.21].

CONCLUSIONS: Our findings showed that ALS patients have a sonographically smaller nerve size than healthy controls. Therefore, this is a potential marker for neuronal diseases.}, } @article {pmid40558500, year = {2025}, author = {Mai, HA and Thomas, CM and Nge, GG and Elefant, F}, title = {Modulating Cognition-Linked Histone Acetyltransferases (HATs) as a Therapeutic Strategy for Neurodegenerative Diseases: Recent Advances and Future Trends.}, journal = {Cells}, volume = {14}, number = {12}, pages = {}, pmid = {40558500}, issn = {2073-4409}, support = {RF1 NS095799/NS/NINDS NIH HHS/United States ; 2RF1NS095799//National Institutes of Health NINDS/ ; 2RF1NS095799/NS/NINDS NIH HHS/United States ; }, mesh = {Humans ; *Neurodegenerative Diseases/therapy/enzymology/drug therapy ; *Histone Acetyltransferases/metabolism ; *Cognition/physiology ; Animals ; Protein Processing, Post-Translational ; Histones/metabolism ; Epigenesis, Genetic ; Acetylation ; Aging ; }, abstract = {Recent investigations into the neuroepigenome of the brain are providing unparalleled understanding into the impact of post-translational modifications (PTMs) of histones in regulating dynamic gene expression patterns required for adult brain cognitive function and plasticity. Histone acetylation is one of the most well-characterized PTMs shown to be required for neuronal function and cognition. Histone acetylation initiates neural circuitry plasticity via chromatin control, enabling neurons to respond to external environmental stimuli and adapt their transcriptional responses accordingly. While interplay between histone acetylation and deacetylation is critical for these functions, dysregulation during the aging process can lead to significant alterations in the neuroepigenetic landscape. These alterations contribute to impaired cognitive functions, neuronal cell death, and brain atrophy, all hallmarks of age-related neurodegenerative disease. Significantly, while age-related generation of DNA mutations remains irreversible, most neuroepigenetic PTMs are reversible. Thus, manipulation of the neural epigenome is proving to be an effective therapeutic strategy for neuroprotection in multiple types of age-related neurodegenerative disorders (NDs) that include Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic lateral sclerosis (ALS) and Huntington's disease (HD). Here, we highlight recent progress in research focusing on specific HAT-based neuroepigenetic mechanisms that underlie cognition and pathogenesis that is hallmarked in age-related NDs. We further discuss how these findings have potential to be translated into HAT-mediated cognitive-enhancing therapeutics to treat these debilitating disorders.}, } @article {pmid40557915, year = {2025}, author = {Ranieri, F and Senerchia, G and Bonan, L and Casali, S and Cabona, C and Cantone, M and De Marchi, F and Diamanti, L and Doretti, A and Fini, N and Filosto, M and Fortuna, A and Iovino, A and Iuzzolino, VV and Lanza, G and Lunetta, C and Maderna, L and Mandrioli, J and Mazzini, L and Musumeci, G and Nuredini, A and Sorarù, G and Toriello, A and Ticozzi, N and Todisco, M and Vacchiano, V and Zinno, L and Silani, V and Rossi, S and Di Lazzaro, V and Dubbioso, R and , }, title = {Cortical Excitability as a Prognostic and Phenotypic Stratification Biomarker in Amyotrophic Lateral Sclerosis.}, journal = {Annals of neurology}, volume = {}, number = {}, pages = {}, doi = {10.1002/ana.27305}, pmid = {40557915}, issn = {1531-8249}, abstract = {OBJECTIVE: Despite its clinical heterogeneity, amyotrophic lateral sclerosis is unified by early and prominent alterations in cortical excitability, increasingly recognized as contributors to disease progression. This study assessed whether the ratio between motor evoked potential (MEP) amplitude, reflecting upper motor neuron integrity, and compound muscle action potential (CMAP) amplitude, indexing lower motor neuron function, could provide an accessible marker of corticospinal excitability to stratify patients by phenotype, stage, and survival.

METHODS: In this multicenter retrospective study, 743 amyotrophic lateral sclerosis patients from 16 tertiary centers in Italy were analyzed. The MEP:CMAP ratio, recorded from upper limb muscles, was categorized as hyperexcitable, normal, or hypoexcitable. Phenotypes included progressive muscular atrophy (or lower motor neuron), flail arm/leg, classic, bulbar, patient with predominant upper motor neuron signs (or pyramidal), and primary lateral sclerosis. Disease stage was assessed using King's staging. Survival was analyzed using Kaplan-Meier curves and Cox regression models.

RESULTS: The MEP:CMAP ratio differed significantly across phenotypes (p < 0.0001), with hyperexcitability predominating in lower motor neuron, flail, classic, and bulbar forms, and hypoexcitability in pyramidal and primary lateral sclerosis. Hypoexcitability increased in advanced King's stages (p < 0.0001). Hyperexcitable patients had shorter survival (p = 0.004), including when tested within 1 year of onset (p = 0.006). Cox regression identified the MEP:CMAP ratio as an independent survival predictor (HR 1.84, 95% CI 1.12-3.03, p = 0.016).

INTERPRETATION: This real-world study supports the clinical value of the MEP:CMAP ratio as a scalable biomarker of cortical excitability in amyotrophic lateral sclerosis, with prognostic relevance across phenotypes and disease stages. ANN NEUROL 2025.}, } @article {pmid40555967, year = {2025}, author = {Ahmed, AB and Draz, ME and Asad, H and Naguib, IA and Edrees, FH}, title = {Innovative Synchronous Spectrofluorometric Method for Assessing a Novel Drug Combination in Amyotrophic Lateral Sclerosis: In Vivo Human Application With Greenness and Sustainability Evaluation.}, journal = {Luminescence : the journal of biological and chemical luminescence}, volume = {40}, number = {6}, pages = {e70222}, doi = {10.1002/bio.70222}, pmid = {40555967}, issn = {1522-7243}, support = {TU-DSPP-2024-49//Taif University/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/drug therapy ; Humans ; Spectrometry, Fluorescence/methods ; *Celecoxib/analysis/therapeutic use/administration & dosage/blood ; *Ciprofloxacin/analysis/therapeutic use/blood/administration & dosage ; Drug Combinations ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a severe neurological disorder that causes damage to sensory neurons, then paralysis and death. A novel combination of celecoxib (CXP) and ciprofloxacin (CIP) has recently been used to enhance both motor performance and CNS cell morphology, alterations in the rate of disease progression, quality of life, and survival, which passed phase IIb RCT study. Celecoxib is classified as a non-steroidal anti-inflammatory drug; ciprofloxacin is a fluoroquinolone antibiotic that has a synergistic effect for the treatment of ALS, which is a severe neurological disorder. A new sustainable, simple, sensitive, and environmentally friendly synchronous spectrofluorimetric approach (SSF) was established to simultaneously estimate celecoxib and ciprofloxacin in pure form and biological fluids. The approach depends on synchronous fluorescence spectroscopy, where CXP and CIP were detected at 364 and 438 nm, correspondingly, using Δλ of 80-nm utilizing sodium dodecyl sulphate (SDS) micellar system, which considerably improved synchronous fluorescence intensity. The approach was validated and revealed excellent linearity with concentrations varying from 10 to 10,000 and 5 to 20,000 ng/mL for CXP and CIP; correspondingly, CXP and CIP showed extremely low limits of detection (LODs) 0.58-0.24 ng/mL, which guarantee the sensitivity of the proposed approach. The suggested approach was successfully implemented to analyze the co-administered pharmaceuticals in their pure form and actual human plasma after concurrent oral administration of both drugs, which may be employed in an inquiry on the pharmacokinetics and bioavailability of human plasma to the new coming PrimeC pharmaceutical formulation. Ultimately, the method's remarkable greenness was proved by evaluating its greenness profile using various assessment strategies. The findings revealed that the SSF approach is a sustainable and environmentally friendly analytical approach.}, } @article {pmid40555518, year = {2025}, author = {Zanella, P and Loss, I and Parlato, R and Weishaupt, JH and Sala, C and Verpelli, C and Boeckers, TM and Catanese, A}, title = {ALS Mutations Shift the Isoelectric Point of the KIF5A C Terminal Inducing Protein Aggregation and TDP-43 Mislocalization.}, journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, volume = {45}, number = {31}, pages = {}, pmid = {40555518}, issn = {1529-2401}, mesh = {*Kinesins/genetics/metabolism/chemistry ; Humans ; *Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology ; *DNA-Binding Proteins/metabolism/genetics ; *Mutation/genetics ; Motor Neurons/metabolism ; Animals ; *Protein Aggregation, Pathological/genetics/metabolism ; Cells, Cultured ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by death of lower and upper motor neurons. Although the mechanism behind the selective neuron loss is still unclear, several heterogeneous genes have been causally linked to ALS. KIF5A encodes for a neuronally enriched kinesin involved in protein transport, and mutations within this gene have been causally linked to different motor neuron diseases. The mutations identified in ALS patients are mostly predicted to alter its mRNA splicing, leading to a frameshift mutation and an aberrant 39-aa-long sequence in the C-terminal domain of KIF5A. Here we found that ALS-related KIF5A mutations induce the accumulation of the mutant form of the protein in human motoneurons, which are also characterized by the cytosolic mislocalization of TDP-43. This ALS hallmark was even exacerbated upon overexpression of the ALS-KIF5A protein in cells differentiated from healthy controls and primary neurons, suggesting a pathological connection between the cellular load of the mutant protein and TDP-43 pathology. While the terminal domain of the WT isoform is characterized by an acid isoelectric point (pI), the ALS variant presents a basic pI due to the altered aminoacidic composition of this sequence. We thus generated a KIF5A-ALS isoform that retained part of the aberrant sequence but with lower pI. The overexpression of this mutated variant led to significantly lower protein aggregation and TDP-43 mislocalization than the ALS mutant. Our data show that re-establishing the correct pI rescues KIFA aggregation and significantly reduces the cytoplasmic mislocalization of TDP-43.}, } @article {pmid40555284, year = {2025}, author = {Park, KH and Kim, KW}, title = {Optogenetics to biomolecular phase separation in neurodegenerative diseases.}, journal = {Molecules and cells}, volume = {48}, number = {8}, pages = {100247}, pmid = {40555284}, issn = {0219-1032}, mesh = {*Optogenetics/methods ; Humans ; *Neurodegenerative Diseases/metabolism/genetics ; Animals ; Phase Separation ; }, abstract = {Neurodegenerative diseases involve toxic protein aggregation. Recent evidence suggests that biomolecular phase separation, a process in which proteins and nucleic acids form dynamic, liquid-like condensates, plays a key role in this aggregation. Optogenetics, originally developed to control neuronal activity with light, has emerged as a powerful tool to investigate phase separation in living systems. This is achieved by fusing disease-associated proteins to light-sensitive oligomerization domains, enabling researchers to induce or reverse condensate formation with precise spatial and temporal control. This review highlights how optogenetic systems such as OptoDroplet are being used to dissect the mechanisms of neurodegenerative disease. We examine how these tools have been applied in models of neurodegenerative diseases, such as amyotrophic lateral sclerosis, Alzheimer's, Parkinson's, and Huntington's disease. These studies implicate small oligomeric aggregates as key drivers of toxicity and highlight new opportunities for therapeutic screening. Finally, we discuss advances in light-controlled dissolution of condensates and future directions for applying optogenetics to combat neurodegeneration. By enabling precise, dynamic control of protein phase behavior in living systems, optogenetic approaches provide a powerful framework for elucidating disease mechanisms and informing the development of targeted therapies.}, } @article {pmid40554516, year = {2025}, author = {Castro, J and de Carvalho, M}, title = {Nerve Conduction Studies of Phrenic Nerve: Normative Data.}, journal = {Journal of clinical neurophysiology : official publication of the American Electroencephalographic Society}, volume = {}, number = {}, pages = {}, doi = {10.1097/WNP.0000000000001181}, pmid = {40554516}, issn = {1537-1603}, abstract = {INTRODUCTION: In neuromuscular diseases, respiratory failure is a major complication. Pulmonary function tests are generally used to assess respiratory function but can be influenced by a number of factors. Nerve conduction studies of the phrenic nerve (PN) is a simple, noninvasive, and safe method to assess diaphragm compromise in neuromuscular diseases.

METHODS: A group of 132 (78 males) healthy subjects, aged between 23 and 90 years, was studied, with bilateral stimulation of the PN, with recording of diaphragm motor responses. Anthropometric variables (sex, age, height, and weight) were collected, and their influence on diaphragm motor response was assessed. Side-to-side differences were also analyzed.

RESULTS: PN compound muscle action potential (CMAP) had significantly higher amplitude and area on the left side. Men had longer latency, and higher amplitude and area when compared with women, on both sides. Age was a significant factor influencing CMAP latency, with an average increase of 0.25 ms per decade of life. In men, a latency longer than 9.5 ms and a CMAP amplitude lower than 0.62 mV should be considered abnormal, while in women, the values are 8.5 ms and 0.48 mV, respectively.

CONCLUSIONS: PN conduction studies offer a simple and reliable technique readily applicable in clinical settings. Diaphragm CMAP parameters are significantly influenced by the anthropometric variables of sex and age. Notably, CMAP amplitude and area are greater for the left PN.}, } @article {pmid40554439, year = {2025}, author = {Fan, Y and Wang, Z and Wu, M and Lin, L and Chen, L and Zheng, B}, title = {Bidirectional Causal Relationship Between Myopia and Neurodegenerative Diseases: Two-Sample Mendelian Randomization Analyses.}, journal = {British journal of hospital medicine (London, England : 2005)}, volume = {86}, number = {6}, pages = {1-19}, doi = {10.12968/hmed.2025.0183}, pmid = {40554439}, issn = {1750-8460}, mesh = {Humans ; Mendelian Randomization Analysis ; *Myopia/genetics/epidemiology ; Genome-Wide Association Study ; *Neurodegenerative Diseases/genetics/epidemiology ; Genetic Predisposition to Disease ; Parkinson Disease/genetics/epidemiology ; Polymorphism, Single Nucleotide ; Alzheimer Disease/genetics/epidemiology ; Amyotrophic Lateral Sclerosis/genetics/epidemiology ; }, abstract = {Aims/Background Myopia is highly prevalent in certain neurodegenerative diseases (NDDs), and both conditions demonstrate genetic susceptibility. This study investigated the potential bidirectional causal relationships between myopia and four NDDs, Parkinson's disease (PD), Alzheimer's disease (AD), multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS), using Mendelian randomization (MR). We aimed to determine whether myopia contributes to the risk of NDDs and vice versa. Methods We analyzed data from two independent, large-scale genome-wide association study (GWAS) cohorts on myopia, comprising 212,571 participants in the first cohort (finn-b-H7_MYOPIA) and 95,619 in the second (GCST009521). GWAS summary statistics for the four NDDs, encompassing 589,439 samples, were also incorporated. Bidirectional MR was employed to investigate causal relationships between myopia and each of the four NDDs. The inverse variance-weighted (IVW) method served as the primary analytical approach. Sensitivity analyses, including MR-Egger regression, weighted median, weighted mode, and simple mode, were conducted to assess the robustness of the findings. Horizontal pleiotropy was evaluated using the MR-Egger regression intercept test and the Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) global test, while heterogeneity was assessed via Cochran's Q test. Leave-one-out analyses were conducted to evaluate the influence of individual single nucleotide polymorphisms (SNPs). Odds ratios (ORs) with 95% confidence intervals (CIs) were reported, and statistical significance was set at p < 0.05. Results MR analyses identified no evidence of a causal relationship between myopia and refractive error and increased risk of any of the four NDDs (all p > 0.05). Similarly, none of the NDDs were associated with an increased risk of myopia or refractive error (all p > 0.05). Sensitivity analyses revealed no SNPs with significant influence on the causal associations (all p > 0.05), supporting the robustness of the findings. Conclusion This study provides no evidence of a bidirectional causal relationship between myopia and the four NDDs among individuals of European ancestry. Future research should extend beyond direct causal inference to investigate potential mediating biological mechanisms.}, } @article {pmid40553568, year = {2025}, author = {Bekier, ME and Pinarbasi, ES and Krishnan, G and Mesojedec, JJ and Hurley, M and Harikumar Sheela, H and Collins, CA and Ghaffari, LT and de Majo, M and Ullian, EM and Koontz, M and Coleman, S and Li, X and Tank, EM and Waksmacki, J and Gao, FB and Barmada, SJ}, title = {Nemo-like kinase disrupts nuclear import and drives TDP43 mislocalization in ALS.}, journal = {The Journal of clinical investigation}, volume = {}, number = {}, pages = {}, doi = {10.1172/JCI188138}, pmid = {40553568}, issn = {1558-8238}, support = {R44 NS124457/NS/NINDS NIH HHS/United States ; P30 AG072931/AG/NIA NIH HHS/United States ; R01 NS113943/NS/NINDS NIH HHS/United States ; R01 NS097542/NS/NINDS NIH HHS/United States ; R56 NS128110/NS/NINDS NIH HHS/United States ; }, abstract = {Cytoplasmic TDP43 mislocalization and aggregation are pathological hallmarks of amyotrophic lateral sclerosis (ALS). However, the initial cellular insults that lead to TDP43 mislocalization remain unclear. In this study, we demonstrate that Nemo-like kinase (NLK) - a proline-directed serine/threonine kinase - promotes the mislocalization of TDP43 and other RNA-binding proteins by disrupting nuclear import. NLK levels are selectively elevated in neurons exhibiting TDP43 mislocalization in ALS patient tissues, while genetic reduction of NLK reduces toxicity in human neuron models of ALS. Our findings suggest that NLK is a promising therapeutic target for neurodegenerative diseases.}, } @article {pmid40553535, year = {2025}, author = {Ramachandra, K and Narayana, AR and Induraj, A and Pai, R}, title = {Unilateral Vocal Cord Palsy as Presenting Feature of Amyotrophic Lateral Sclerosis.}, journal = {The Journal of the Association of Physicians of India}, volume = {73}, number = {5}, pages = {83-84}, doi = {10.59556/japi.73.0931}, pmid = {40553535}, issn = {0004-5772}, mesh = {Humans ; Male ; *Amyotrophic Lateral Sclerosis/diagnosis/complications ; Aged ; *Vocal Cord Paralysis/etiology/diagnosis ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative pathology marked by the degeneration of upper and lower motor neurons, resulting in muscle weakness and atrophy, impairing motor function. Bulbar-onset ALS is a distinct clinical subtype, with initial involvement of bulbar motor neurons, often causing severe speech and swallowing difficulties. Despite its impact, bulbar-onset ALS, especially with rare symptoms like unilateral vocal cord palsy (UVCP), lacks extensive research. Here, we detail the case of a 79-year-old nonambulatory diabetic male with a 1-year history of hoarseness of voice, diagnosed with bulbar-onset ALS with UVCP. This underscores the importance of recognizing unusual presentations of ALS, particularly in geriatric populations, urging tailored medical evaluations for optimal care and improved outcomes in this challenging neurological condition.}, } @article {pmid40551967, year = {2025}, author = {Berdyński, M and Safranow, K and Andersen, PM and Żekanowski, C}, title = {Phenotypic Characterization of ALS-Causing SOD1 Mutations Affecting Polypeptide Length.}, journal = {Human mutation}, volume = {2025}, number = {}, pages = {9792233}, pmid = {40551967}, issn = {1098-1004}, mesh = {*Amyotrophic Lateral Sclerosis/genetics/mortality ; Humans ; *Superoxide Dismutase-1/genetics/chemistry ; Phenotype ; *Mutation ; Middle Aged ; Female ; Male ; Adult ; Age of Onset ; Aged ; }, abstract = {Background: Some 234 mutations in the small SOD1 gene have been reported to cause amyotrophic lateral sclerosis. However, the pathogenic mechanisms, particularly of those mutations affecting polypeptide length, are contested. It is presently unknown whether all reported nonsense mutations in SOD1 are causative for ALS. The emergence of promising new anti-SOD1 drugs has made it imperative to gain further insight into clinical-genetic aspects of ALS for deciding which patients to treat in clinical practice and include in drug trials. Objective: This study is aimed at comprehensively analyzing the clinical phenotypes associated with ALS-causing SOD1 mutations that alter the polypeptide length. The specific focus is on the age at which symptoms manifest and the survival duration. Methods: Data were collected from web databases, published reports, conference presentations, and personal communications up to November 2023. The clinical endpoints, including age at symptom onset and age at death, were subjected to survival analysis. Comparative analyses were performed between frameshift and nonframeshift variants. Results: A cohort of 146 ALS patients harboring 38 different nonmissense SOD1 variants was analyzed. The mean age of disease onset was 46.9 years, with a mean survival duration of 49 months. Significant heterogeneity was observed in clinical outcomes, with earlier disease onset and reduced survival associated with specific mutations. Notably, frameshift mutations proximal to the N-terminus showed a higher risk of early ALS onset compared to more distal mutations. Conclusions: The clinical phenotypes of ALS patients with nonmissense SOD1 mutations are highly variable and dependent on the specific mutation. These findings underscore the necessity of including diverse SOD1 mutation carriers in therapeutic trials and suggest that both loss-of-function and gain-of-function mechanisms may contribute to ALS pathology.}, } @article {pmid40550228, year = {2025}, author = {Tiwari, A and Singh, B and Singh, GK and Meena, J and Agrawal, AK and Kumar, S and Modi, G}, title = {Unveiling Exosome Potential: Transforming Treatments for Neurodegeneration.}, journal = {ACS applied bio materials}, volume = {8}, number = {7}, pages = {5406-5423}, doi = {10.1021/acsabm.5c00096}, pmid = {40550228}, issn = {2576-6422}, mesh = {*Exosomes/chemistry/metabolism ; Humans ; *Neurodegenerative Diseases/drug therapy/metabolism ; Animals ; *Biocompatible Materials/chemistry ; Drug Delivery Systems ; }, abstract = {Exosomes, tiny extracellular vesicles, hold significant potential as biological nanocarriers for diverse therapeutic agents due to their exceptional ability to navigate through the barriers of biological systems. This comprehensive review delves into the capability of exosomes in the therapy of neurodegenerative disorders, concentrating on their potential for targeted drug delivery. It examines the complex processes involved in exosome-mediated drug delivery, including targeting, cellular uptake, intracellular trafficking, and therapeutic release. Insights from preclinical studies and clinical trials are exploited, highlighting the impactful applications of exosomes, particularly in the treatment of Parkinson's, Alzheimer's, ALS, and Huntington's diseases. The review also addresses challenges such as immunogenicity, scalability, and regulatory obstacles while exploring emerging technologies like advanced exosome engineering, personalized medicine, and the integration of nanotechnology. Overall, this review accentuates the potential impact of exosome-based treatments in biomedicine alongside the critical need to overcome existing barriers.}, } @article {pmid40550045, year = {2025}, author = {Lei, C and Chen, J and Chen, Z and Xiao, Y and Chen, J and Ma, C and Yang, M and Wu, D and Xie, L}, title = {Amyotrophic lateral sclerosis and neurodegenerative diseases: A Mendelian randomization study.}, journal = {Medicine}, volume = {104}, number = {25}, pages = {e42847}, pmid = {40550045}, issn = {1536-5964}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/epidemiology ; *Mendelian Randomization Analysis ; *Neurodegenerative Diseases/genetics/epidemiology ; Parkinson Disease/genetics ; Alzheimer Disease/genetics ; Frontotemporal Dementia/genetics ; }, abstract = {In this study, we used the Mendelian randomization (MR) method to systematically examine whether there is a bidirectional causal relationship between amyotrophic lateral sclerosis (ALS) and Alzheimer's disease (AD), Parkinson's disease (PD), frontotemporal dementia (FTD), multiple system atrophy (MSA), and dementia with Lewy bodies (DLB). We analyzed data from 6,44,924 participants using MR to evaluate causality. We employed inverse variance weighted and MR-Egger regression tests for MR analysis. Additionally, we performed sensitivity analyses using the MR-Egger test and Mendelian Randomization Pleiotropy RESidual Sum and Outlier. The inverse variance weighted analysis found no evidence of a risk effect between ALS and the neurodegenerative diseases AD, PD, FTD, MSA, and DLB. However, the MR-Egger analysis showed that both AD (odds ratio: 1.079, 95% confidence interval: 1.017-1.145, P = .029) and PD (odds ratio: 1.210, 95% confidence interval: 1.046-1.401, P = .020) have a risk effect on ALS, indicating that AD and PD increase the risk of ALS. Our MR analysis suggests that AD and PD may have a potential causal relationship with ALS. Conversely, ALS does not appear to have a causal relationship with the other neurodegenerative diseases examined (FTD, MSA, DLB).}, } @article {pmid40548824, year = {2025}, author = {Leykam, L and Jonsson, PA and Forsberg, KME and Andersen, PM and Brännström, T and Marklund, SL and Zetterström, P}, title = {SOD1 Protein Content in Human Central Nervous System and Peripheral Tissues.}, journal = {Journal of neurochemistry}, volume = {169}, number = {6}, pages = {e70136}, pmid = {40548824}, issn = {1471-4159}, support = {//Olsson och Olsson Välgörenhetsstiftelse/ ; //King Gustaf V:s and Queen Victoria's Freemason's Foundation/ ; //Fort Knox Välgörenhetsstiftelse/ ; 2.1.12-1605-14//Umeå University Insamlingsstiftelsen/ ; 2.1.6-452-20//Umeå University Insamlingsstiftelsen/ ; 223-1881-13//Umeå University Insamlingsstiftelsen/ ; 223-2808-12//Umeå University Insamlingsstiftelsen/ ; //Västerbotten Läns Landsting/ ; //Ulla-Carin Lindquists stiftelse för ALS-forskning/ ; //Neuroförbundet/ ; 2012-3167//Vetenskapsrådet/ ; 2017-03100//Vetenskapsrådet/ ; 2012.0091//Knut och Alice Wallenbergs Stiftelse/ ; 2014.0305//Knut och Alice Wallenbergs Stiftelse/ ; 2020.0232//Knut och Alice Wallenbergs Stiftelse/ ; 2012-0262//Swedish brain foundation/ ; 2012-0305//Swedish brain foundation/ ; 2013-0279//Swedish brain foundation/ ; 2016-0303//Swedish brain foundation/ ; 2020-0353//Swedish brain foundation/ ; }, mesh = {Humans ; *Superoxide Dismutase-1/metabolism ; Amyotrophic Lateral Sclerosis/metabolism/genetics/enzymology ; Male ; Female ; *Central Nervous System/enzymology/metabolism ; Middle Aged ; Aged ; Adult ; *Superoxide Dismutase/metabolism ; Muscle, Skeletal/enzymology ; }, abstract = {Gene silencing therapy is an effective treatment for amyotrophic lateral sclerosis (ALS) patients carrying mutations in the superoxide dismutase-1 (SOD1) gene aiming to reduce noxious forms of SOD1 in the central nervous system (CNS). The normal steady-state level of SOD1 protein in human CNS is therefore of interest but is contested. In this work we have analyzed SOD1 protein content, total protein content, and SOD1 enzymatic activity in six areas of the CNS as well as in four peripheral tissues from sporadic and familial ALS patients and non-ALS controls. Our results show that SOD1 in the human CNS constitutes around 100 μg/g wet weight corresponding to about 0.16% of the total protein in the studied areas. Of the peripheral tissues analyzed, kidney and erythrocytes contain roughly equal amounts, liver higher, and skeletal muscle lower levels of SOD1 compared to the CNS. This data shows SOD1 protein levels around 10 times lower compared to previously published figures. However, SOD1 can still be considered an abundant protein considering that > 12 000 proteins are expressed in human cells. There was no difference in SOD1 protein content between sporadic or familial ALS patients and control individuals. The level and activity of SOD1 are not deviating in the areas of the CNS that are most vulnerable to ALS. Instead, insufficient control of SOD1 structure and aggregation could be important factors behind the vulnerability of motor areas to SOD1 proteotoxicity.}, } @article {pmid40547142, year = {2025}, author = {Kumar, S}, title = {Esophageal squamous cell carcinoma susceptibility of activin A receptor type 1C variants in Chinese population.}, journal = {World journal of gastrointestinal oncology}, volume = {17}, number = {6}, pages = {102687}, pmid = {40547142}, issn = {1948-5204}, abstract = {Lin et al's investigation on the association of activin A receptor type 1C (ACVR1C) (transforming growth factor beta type I receptor) single nucleotide polymorphisms (SNPs) with esophageal squamous cell carcinoma (ESCC) risk in the Chinese population is a scientific approach. This study explores the susceptibility of ACVR1C polymorphism towards ESCC in the Chinese population, highlighting the polymorphism's potentiality as an early diagnostic and therapeutic target. The author assessed about a thousand ESCC Chinese patients' samples for ACVR1C SNPs in a hospital-based cohort study using the ligation detection reaction method. Further, the hypothesis was tested using appropriate statistical genetic models and stratified analysis. ACVR1C SNPs can help assess ESCC susceptibility stratification and provide valuable information for individual diagnosis and treatment of ESCC patients. In order to account for confounding variables, find genuine SNP-disease relationships, boost statistical power, and make biological interpretation easier, it is imperative that genetic association studies of ESCC incorporate pertinent clinical aspects.}, } @article {pmid40544342, year = {2025}, author = {Rodríguez-García, V and Venta-Sobero, JA and Chima-Galán, MDC}, title = {A novel heterozygous variant of FUS gene associated with juvenile ALS and premature tremor onset: a case report.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {}, number = {}, pages = {1-3}, doi = {10.1080/21678421.2025.2522403}, pmid = {40544342}, issn = {2167-9223}, abstract = {Juvenile amyotrophic lateral sclerosis (JALS) is neurodegenerative disease of the upper and lower motor neurons of rare incidence. Although fused in sarcoma (FUS) mutations in JALS patients have been associated with movement disorders, here we described the case of a young girl with very early onset of tremor, years before commencement of weakness; once symptoms of JALS were stablished, a typical rapid disease progression from spinal to bulbar symptoms were noticed. Genetic testing revealed a novel mutation in FUS gene causative of a protein dysfunction. This case emphasizes the fact that some mutations within the FUS in JALS patients may produce a symptom onset with tremor.}, } @article {pmid40545904, year = {2025}, author = {Mitsumoto, H and Cheung, K and Oskarsson, B and Jang, GE and Andrews, HF and Johnson, S and Shah, JS and Fernandes, JA and Andrews, JA and Rao, M and McElhiney, M}, title = {Placebo-Controlled, Randomized Double-Blind N-Of-1 Trial to Study Safety and Potential Efficacy of TJ-68 for Improving Muscle Cramps in Patients With Amyotrophic Lateral Sclerosis: A Pilot Study.}, journal = {Muscle & nerve}, volume = {72}, number = {3}, pages = {485-492}, pmid = {40545904}, issn = {1097-4598}, mesh = {Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; *Amyotrophic Lateral Sclerosis/complications/drug therapy ; Cross-Over Studies ; Double-Blind Method ; *Muscle Cramp/drug therapy/etiology ; Pilot Projects ; Treatment Outcome ; Single-Case Studies as Topic ; }, abstract = {INTRODUCTION/AIMS: Muscle cramps are a common symptom in amyotrophic lateral sclerosis (ALS). Ameliorating muscle cramps may improve quality of life in devastating diseases like ALS. A traditional Japanese medicine (Kampo, TJ-68) is widely prescribed in Japan for muscle cramps. However, it is not available in the USA. This study evaluated the safety, tolerability, and efficacy of TJ-68 in ALS.

METHODS: This study was a double-blind, randomized, placebo-controlled crossover trial, consisting of four periods, conducted at three centers in the USA. Safety was evaluated using multiple measures. The primary efficacy outcome was the Visual Analog Scale for Muscle Cramps Affecting Overall Daily Activity (item #5 of the Muscle Cramp Scale (MCS)). The secondary outcomes included the remaining items of the MCS and the Clinical Global Impression of Changes (CGIC), among others. The study was planned to enroll 22 participants with ALS within 2 years.

RESULTS: The enrollment was slow and was completed with 11 participants. There were no serious safety issues and TJ-68 was well tolerated. Although the primary outcome measure did not reach statistical significance (p = 0.35), several secondary measures showed significant results: MCS #1 triggering of cramps (p = 0.01), MCS #2 cramp frequency (p = 0.03), MCS Additional 1 change of motor behaviors (p = 0.02), and CGIC assessed by the evaluator (p = 0.009). Other outcome measures did not reach statistical significance.

DISCUSSION: The study revealed that N-of-1 trial design can detect changes in a small sample size, and TJ-68 appeared to be safe. Larger studies are needed to confirm the efficacy of TJ-68.}, } @article {pmid40544973, year = {2025}, author = {Thakur, N and Kumar, T and Singh, C and Kumar, R and Kumar, A}, title = {Cell membrane-coated nanoparticles for neurodegenerative disorders management.}, journal = {International journal of pharmaceutics}, volume = {681}, number = {}, pages = {125875}, doi = {10.1016/j.ijpharm.2025.125875}, pmid = {40544973}, issn = {1873-3476}, mesh = {Humans ; *Neurodegenerative Diseases/drug therapy ; Animals ; *Cell Membrane/metabolism/chemistry ; *Nanoparticles/chemistry/administration & dosage ; Drug Delivery Systems/methods ; Blood-Brain Barrier/metabolism ; Drug Carriers/chemistry ; *Nanoparticle Drug Delivery System/chemistry ; }, abstract = {Neurodegenerative disorders (ND) are accompanied by neuronal death because of progressive destruction in neuronal structure and function. Due to various neurological conditions, there is a significant number of deaths every year around the world. The healthcare burden is also increasing each year. Development and progress in nanotechnology enable the creation of nanocarriers that transport drugs to the site of disease, thereby enhancing the therapeutic performance of the drug. However, the transport of nanocarrier-based therapeutics to the brain is restricted by barriers such as the Blood-Brain Barrier (BBB) and Blood-Cerebrospinal Fluid Barrier (BCFB), which are further impeded by P-glycoproteins. Hence, current research and development focus on overcoming these obstacles. A biomimetic drug delivery system is one of the best ways to overcome these challenges. One of the promising biomimetic drug delivery systems is cell membrane-coated nanoparticles. In this review, we have comprehensively reviewed the recent progress and development in various cell membrane coated nanoparticle-based drug delivery systems for the effective management of a range of neurodegenerative diseases such as Alzheimer's Disease, Parkinson's Disease, Glioblastoma, Ischemic Stroke, Huntington's Disease, Amyotrophic Lateral Sclerosis, Glioma, Peripheral Nerve Injury, and Motor Neuron Disorder. We also reviewed the challenges associated with cell membrane-coated nanoparticles, such as biosafety hurdles, toxicity, regulatory requirements, and clinical translation. Ultimately, we provided the conclusions and future research directions that must be investigated to overcome the current limitations.}, } @article {pmid40544604, year = {2025}, author = {Jonk, SM and Nicol, A and Chrysostomou, V and Lardner, E and Yu, SC and Stålhammar, G and Crowston, JG and Tribble, JR and Swoboda, P and Williams, PA}, title = {Metabolic analysis of sarcopenic muscle identifies positive modulators of longevity and healthspan in C. elegans.}, journal = {Redox biology}, volume = {85}, number = {}, pages = {103732}, pmid = {40544604}, issn = {2213-2317}, abstract = {Sarcopenia is the age-related degeneration of skeletal muscle, resulting in loss of skeletal muscle tone, mass, and quality. Skeletal muscle is a source of systemic metabolites and macromolecules important for neuronal health, function, and healthy neuronal aging. Age-related loss of skeletal muscle might result in decreased metabolite and macromolecule availability, resulting in reduced neuronal function or increased susceptibility to unhealthy aging and neurodegenerative diseases. We aimed to identify muscle metabolite candidates that regulate healthy aging. C57BL/6J mice were aged to young adult (4 months) and old age (25 months) and skeletal muscle was collected. Age-related muscle loss was confirmed by reduced muscle mass, muscle fiber degeneration, reduced myosin intensity, in addition to a metabolic shift and increased DNA damage in skeletal muscle. Using a low molecular weight enriched metabolomics protocol, we assessed the metabolic profile of skeletal muscle from young adult and old age mice and identified 20 metabolites that were significantly changed in aged muscle. These metabolite candidates were tested in C. elegans assays of lifespan, healthspan, muscle, and mitochondrial morphology under normal and stressed conditions. We identified four metabolite candidates (beta-alanine, 4-guanidinobutanoic acid, 4-hydroxyproline, pantothenic acid) that, when supplemented in C. elegans provided robust gero- and mitochondrial protection. These candidates also affected life-, and health- span in C. elegans models of amyotrophic lateral sclerosis (ALS) and Duchenne muscular dystrophy (DMD). Our findings support that aging muscle can be used to identify novel metabolite modulators of lifespan and health and may show promise for future treatments of neurodegenerative and neuromuscular disorders.}, } @article {pmid40543671, year = {2025}, author = {Kim, RW and Mesinkovska, NA and Min, MS}, title = {Limitations in insurance coverage for management of alopecia, a response to Brinks et al's letter.}, journal = {Journal of the American Academy of Dermatology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jaad.2025.06.043}, pmid = {40543671}, issn = {1097-6787}, } @article {pmid40543477, year = {2025}, author = {Scott, J and Crook-Rumsey, M and Carobin, A and Bilgorai, J and Kelly, G and Sreedharan, J and Shaw, C and Bashford, J}, title = {Noninvasive quantification of fasciculations to track tofersen therapy in superoxide dismutase 1 amyotrophic lateral sclerosis.}, journal = {Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology}, volume = {177}, number = {}, pages = {2110791}, doi = {10.1016/j.clinph.2025.2110791}, pmid = {40543477}, issn = {1872-8952}, } @article {pmid40543321, year = {2025}, author = {Zou, T and Hou, M and Han, H and Wang, X and Chen, H and Tang, Y and Li, R and Hu, S}, title = {Medulla oblongata dominated synaptic density network degeneration in amyotrophic lateral sclerosis.}, journal = {NeuroImage. Clinical}, volume = {47}, number = {}, pages = {103814}, pmid = {40543321}, issn = {2213-1582}, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a brain network disorder closely associated with synaptic loss in the upper and lower motor neurons. However, the in vivo synaptic network changes and their progressive processes remain unclear. Here, we aim to investigate the synaptic density network connectivity and the likely sequences of synaptic loss in patients with ALS.

METHODS: We examined data from 21 patients diagnosed with ALS and 25 sex- and age-matched healthy controls (HCs) who underwent PET imaging with the SV2A radioligand [[18]F]SynVesT-1. The individual synaptic density similarity network was constructed for each patient by calculating the similarity between interregional synaptic density distributions. The synaptic network connectivity changes were investigated, followed by an examination of the local synaptic density in regions that showed significant network alterations. Finally, we constructed the voxel-wise and ROI-wise causal synaptic covariance network (cSCN) by applying Granger causality analysis. This allowed us to identify the sequence of synaptic loss in these brain regions.

RESULTS: We observed an overall decrease in synaptic density network connectivity in ALS patients compared to controls, with the highest nodal degree in the right medulla oblongata. Specifically, the reduced connections were dominantly between the medulla oblongata and the striatum, frontal lobe, occipital lobe, as well as between the striatum and the frontal lobe, occipital lobe. Furthermore, patients with ALS displayed significantly synaptic loss in those brain regions. The cSCN analyses showed that as the disease progresses, the cortical synaptic loss sequences of ALS extend from the medulla oblongata to the regions including the striatum, frontal lobe, occipital lobe, and parietal lobe.

CONCLUSIONS: These findings suggest that synaptic density network degeneration in ALS may follow a bottom-up transmission pattern, primarily involving in the medulla oblongata-striatum-neocortex network, which have the potential to capture new network-based targets for clinical therapy in the progression of ALS.}, } @article {pmid40542195, year = {2025}, author = {Zhang, J and Hu, J and Liu, R and Zhou, T and Luo, X and Liang, P and Xie, Z and Zhao, Q and Chen, Y and Du, D and Liu, C and Zheng, Y and Li, D and Wang, B}, title = {YAP maintains the dynamics of TDP-43 condensates and antagonizes TDP-43 pathological aggregates.}, journal = {Nature cell biology}, volume = {27}, number = {7}, pages = {1148-1160}, pmid = {40542195}, issn = {1476-4679}, support = {32470726//National Natural Science Foundation of China (National Science Foundation of China)/ ; 32000727//National Natural Science Foundation of China (National Science Foundation of China)/ ; 82188101//National Natural Science Foundation of China (National Science Foundation of China)/ ; 32171236//National Natural Science Foundation of China (National Science Foundation of China)/ ; 32370731//National Natural Science Foundation of China (National Science Foundation of China)/ ; 32170683//National Natural Science Foundation of China (National Science Foundation of China)/ ; 82372788//National Natural Science Foundation of China (National Science Foundation of China)/ ; 2023J01024//Natural Science Foundation of Fujian Province (Fujian Provincial Natural Science Foundation)/ ; JCYJ20220531100204010//Shenzhen Science and Technology Innovation Commission/ ; 20XD1425000//Science and Technology Commission of Shanghai Municipality (Shanghai Municipal Science and Technology Commission)/ ; 22JC1410400//Science and Technology Commission of Shanghai Municipality (Shanghai Municipal Science and Technology Commission)/ ; }, mesh = {*DNA-Binding Proteins/metabolism/genetics ; Humans ; Animals ; *Amyotrophic Lateral Sclerosis/metabolism/pathology/genetics ; YAP-Signaling Proteins ; Phosphorylation ; *Adaptor Proteins, Signal Transducing/metabolism/genetics ; Transcription Factors/metabolism ; Drosophila Proteins/metabolism/genetics ; HEK293 Cells ; Drosophila melanogaster/metabolism/genetics ; Animals, Genetically Modified ; Cell Cycle Proteins ; Stress Granules/metabolism/pathology ; Protein Aggregation, Pathological/metabolism ; Mice ; *Phosphoproteins/metabolism/genetics ; Nuclear Proteins/metabolism/genetics ; Disease Models, Animal ; *Biomolecular Condensates/metabolism ; }, abstract = {Recent studies exploring the underlying pathomechanisms of amyotrophic lateral sclerosis (ALS), a fatal motor neuron disorder, have focused on biomolecular condensates. Here we reveal an unexpected function for YAP, a central component of the Hippo pathway, in regulating the dynamic behaviour of stress granules and TDP-43 condensates, a role that is independent of its transcriptional activity in the Hippo pathway. YAP directly binds to TDP-43. This interaction directly promotes the homotypic multimerization and phase separation of TDP-43 while inhibiting its hyperphosphorylation and solidification under stress conditions. Remarkably, YAP, whose messenger RNA levels are reduced in patients with ALS, is found to co-localize with pathological hyperphosphorylated TDP-43 aggregates in the brains of patients with ALS. In addition, elevation of YAP/Yorkie (a fly homologue of mammalian YAP) expression substantially reduces TDP-43 toxicity in primary neuron and transgenic fly models of ALS. Our findings highlight an unexpected role of YAP in managing ALS-associated biomolecular condensates, presenting important implications for potential ALS treatments.}, } @article {pmid40542104, year = {2025}, author = {Temp, AGM and Tarakdjian, GN and Kasper, E and Machts, J and Kaufmann, J and Vielhaber, S and Prudlo, J and Cole, JH and Dyrba, M and Teipel, S and Hermann, A}, title = {The role of cognitive and brain reserve in the clinical presentation and progression of amyotrophic lateral sclerosis.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {20232}, pmid = {40542104}, issn = {2045-2322}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology/psychology/pathology ; *Cognitive Reserve/physiology ; Disease Progression ; Male ; Female ; Middle Aged ; *Brain/physiopathology/pathology ; Aged ; Cognitive Dysfunction/physiopathology ; *Cognition ; Frontotemporal Dementia/physiopathology ; }, abstract = {Recent research has shown that cognitive reserve is associated with better cognitive abilities in ALS/MND, and that a slow brain ageing speed is associated with intact cognition in ALS. This study compares the effects of cognitive reserve and the predicted brain age difference (PAD) on the risk of being diagnosed with ALS, the risk of having cognitive or behavioral impairment, or even fronto-temporal dementia, and on disease duration.Our results indicated that neither PAD nor cognitive reserve was associated with an increased risk of ALS, but that higher PAD was associated with an increased risk of cognitive impairments and FTD, as well as a shortened disease duration. Higher cognitive reserve on the other hand was associated with a lower risk of cognitive impairment and a longer disease duration.Brain age as a proxy of brain reserve influences disease progression and presentation more strongly than cognitive reserve.}, } @article {pmid40541317, year = {2025}, author = {Frecska, E and Kovács, A and Szabo, A}, title = {The protective effect of DMT against neurodegeneration.}, journal = {International review of neurobiology}, volume = {181}, number = {}, pages = {395-420}, doi = {10.1016/bs.irn.2025.04.010}, pmid = {40541317}, issn = {2162-5514}, mesh = {Humans ; Animals ; *Neurodegenerative Diseases/metabolism/drug therapy/prevention & control ; *Neuroprotective Agents/therapeutic use/pharmacology ; *Receptors, sigma/agonists/metabolism ; *Reperfusion Injury/metabolism/drug therapy ; Sigma-1 Receptor ; }, abstract = {This paper explores the therapeutic potential of DMT in neuroprotective strategies, particularly concerning ischemia-reperfusion injury (IRI) and neurodegenerative disorders. Besides its potent serotonin receptor actions, DMT is also an endogenous agonist of the sigma-1 receptor (Sig-1R). Sigma receptors are a unique family of proteins with high expression in the brain and spinal cord and have been involved in the etiology, symptom course and treatment of several central nervous system disorders. Our previous theoretical and experimental work strongly suggest that targeting sigma (and serotonin) receptors via DMT may be particularly useful for treatment in a number of neurological conditions like stroke, global brain ischemia, Alzheimer's disease, and amyotrophic lateral sclerosis. In this article, we briefly overview the function of Sig1-R in cellular bioenergetics with a focus on the processes involved in IRI and summarize the results of our previous preclinical (in vitro and in vivo) DMT studies aiming at mitigating IRI and related cellular neuropathologies. We conclude that the effect of DMT may involve a universal role in cellular protective mechanisms suggesting therapeutic potentials against different components and types of IRIs emerging in local and generalized brain ischemia after stroke or cardiac arrest. The multiple neuroprotective mechanisms facilitated by DMT may position it as a model molecule for developing pharmacological treatments for neurodegenerative disorders.}, } @article {pmid40541245, year = {2025}, author = {Vázquez, MC and Perna, A and Legnani, M and Saona, G}, title = {Prognostic factors in ALS: different approaches to the same problem.}, journal = {Arquivos de neuro-psiquiatria}, volume = {83}, number = {6}, pages = {1-7}, pmid = {40541245}, issn = {1678-4227}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/mortality/diagnosis ; Female ; Male ; Middle Aged ; Prognosis ; Uruguay/epidemiology ; Aged ; Disease Progression ; Adult ; Kaplan-Meier Estimate ; Age of Onset ; Proportional Hazards Models ; Time Factors ; }, abstract = {The natural history of amyotrophic lateral sclerosis (ALS), the prognoses, and the survival times are fields of considerable interest that are scarcely studied in South American countries.To describe the survival of a representative cohort of Uruguayan ALS patients, and to identify covariates associated with survival using different analyses.Survival was assessed using the Kaplan-Meier method. Different Cox proportional hazards functions were used to identify independent prognostic predictors since the diagnosis: classic, stratified, and truncated.We included 166 definite and probable ALS patients. The median follow-up was of 13.6 years. An analysis was performed according to the recruitment groups: prevalent, exhaustive incident, and non-exhaustive incident cases. The median survival since the diagnosis was longer in the prevalent group (33 months) than in the exhaustive incident (22 months) and non-exhaustive incident (14 months) groups. The median survival time of the entire cohort from onset to death was 37 months and 23 months from the diagnosis. Factors related to survival from diagnosis to death were: age at onset, bulbar region onset, clinical form, and progression rate.The present study described the role of clinical and demographic factors in ALS survival in the Uruguayan population and shed light on differences involving survival models and the temporal bias produced by the lack of precision in determining the onset of the disease.}, } @article {pmid40541176, year = {2025}, author = {Sonustun, B and Vahsen, BF and Ledesma-Terrón, M and Li, Z and Tuffery, L and Xu, N and Calder, EL and Jungverdorben, J and Weber, L and Zhong, A and Miguez, DG and Monetti, M and Zhou, T and Giacomelli, E and Studer, L}, title = {Telmisartan is neuroprotective in a hiPSC-derived spinal microtissue model for C9orf72 ALS via inhibition of neuroinflammation.}, journal = {Stem cell reports}, volume = {20}, number = {7}, pages = {102535}, pmid = {40541176}, issn = {2213-6711}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; }, mesh = {*Telmisartan/pharmacology ; Humans ; *Induced Pluripotent Stem Cells/metabolism/cytology/drug effects ; *Amyotrophic Lateral Sclerosis/pathology/drug therapy/metabolism/genetics ; *Neuroprotective Agents/pharmacology ; Microglia/drug effects/metabolism ; Motor Neurons/drug effects/metabolism/pathology ; *C9orf72 Protein/genetics/metabolism ; *Spinal Cord/pathology/drug effects/metabolism ; *Neuroinflammatory Diseases/drug therapy/pathology ; Inflammation/drug therapy/pathology ; Astrocytes/drug effects/metabolism ; Angiotensin II Type 1 Receptor Blockers/pharmacology ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive motor neuron (MN) loss. The most common genetic cause, a hexanucleotide repeat expansion in C9orf72 (C9-ALS), disrupts microglial function, contributing to neuroinflammation, a key disease driver. To investigate this, we developed a three-dimensional spinal microtissue (SM) model incorporating human induced pluripotent stem cell (hiPSC)-derived MNs, astrocytes, and microglia. Screening 190 Food and Drug Administration (FDA)-approved compounds, we identified sartans-angiotensin II receptor I blockers (ARBs)-as potent inhibitors of neuroinflammation. Telmisartan, a highly brain-penetrant ARB, significantly reduced the levels of pro-inflammatory cytokines interleukin (IL)-6 and IL-8 and rescued MN loss in C9-ALS SMs. Our findings suggest that C9-ALS microglia drive MN toxicity and that telmisartan can effectively mitigate inflammation and preserve MN viability. This work lays the groundwork for modeling disease-related neuroinflammation and points to telmisartan as a therapeutic candidate worth further exploration for treating C9-ALS.}, } @article {pmid40540646, year = {2025}, author = {Au, CK and Chin, ML and Luk, WL and Wong, KW and Che, LY and Yuan, BF and Ilić, G and Pavlović, M and Chan, HW and Yu, JZ and Pavlović, NM and Cai, Z and Chan, W}, title = {Analysis of Honey and Environmental Samples from BEN Endemic Villages in Serbia: Identification of a Novel Human Exposure Pathway for Aristolochic Acids and Aristolactams.}, journal = {Journal of agricultural and food chemistry}, volume = {73}, number = {26}, pages = {16293-16300}, pmid = {40540646}, issn = {1520-5118}, mesh = {Serbia/epidemiology ; Humans ; *Aristolochic Acids/analysis/toxicity/metabolism ; *Balkan Nephropathy/epidemiology/etiology ; *Aristolochia/chemistry/metabolism ; *Honey/analysis ; *Air Pollutants/analysis ; }, abstract = {Dietary exposure to aristolochic acids (AAs) through AA-tainted flour is closely linked to the development of Balkan endemic nephropathy (BEN), a chronic kidney disease that is prevalent in rural farming villages in the Balkan region; however, additional exposure pathways would better explain the incidence rate of BEN. This study reveals for the first time that inhalation of AA-contaminated air, which often contains aristolactams (ALs)─genotoxic metabolites of AAs─represents an unrecognized exposure route. The presence of AAs was confirmed in local honey, and subsequent analysis of face masks worn by volunteers near flowering Aristolochia clematitis (A. clematitis) weeds indicated that AAs may be airborne. Further investigation into the transport of AA-containing particles was conducted by analyzing outdoor residential surfaces (e.g., windowsills) in Serbia, detecting AA-I or AL-I in more than 20% of the samples, with concentrations ranging from 13 to 2470 pg and 1 to 8985 pg per 225 cm[2], respectively. Additionally, it was found that burning A. clematitis generates particle-bound ALs. Given that A. clematitis weeds are often burned alongside wheat remnants for cooking, heating, and fertilizer production, these findings highlight airborne AAs and ALs as potentially key agents in the induction of BEN. In conjunction with the WHO's notice that biomass burning significantly contributes to the high prevalence of respiratory diseases in the Balkans, this study identifies AAs and their analogs as air pollutants. Therefore, it is imperative to eliminate A. clematitis weeds from affected areas and to cease their use as heating and cooking fuel.}, } @article {pmid40540128, year = {2025}, author = {Bonan, L and Bombardi, M and Di Lionardo, A and Vitiello, M and Morresi, S and Longoni, M}, title = {Co-occurence of amyotrophic lateral sclerosis and sarcoidosis: a case report and systematic review of the literature.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {}, number = {}, pages = {}, pmid = {40540128}, issn = {1590-3478}, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder affecting motor neurons, with 90% of cases being sporadic. Sarcoidosis is an inflammatory disease affecting multiple organs, with neurological complications occurring in 5-10% of patients. Only isolated cases of this extremely rare combination of the two diseases have been reported.

METHODS: We present the case of a 45-year-old man diagnosed with ALS after a 2-year history of progressive upper limb weakness who was incidentally found to be affected by thoraco-abdominal lymphadenopathy. The biopsy confirmed the co-presence of sarcoidosis. We also make a systematic review of the literature of this rare combination.

RESULTS: The patient showed stabilization of the neurological condition and the pneumological disease after administration of immunosuppressive treatment.

CONCLUSION: Our case report and literature review highlight peculiar clinical characteristics of this extremely rare combination of diseases, deepening the understanding of this peculiar phenotype.}, } @article {pmid40539764, year = {2025}, author = {Adler, GL and Kiernan, MC and Tan, RH}, title = {The FindMNDBiomarker Program: Protein Changes in Motor Neuron Disease/Amyotrophic Lateral Sclerosis Postmortem Tissue and Biofluids.}, journal = {Annals of neurology}, volume = {}, number = {}, pages = {}, doi = {10.1002/ana.27300}, pmid = {40539764}, issn = {1531-8249}, support = {IM-202403-01257//FightMND/ ; MCR-77//FightMND/ ; }, abstract = {OBJECTIVE: Biomarkers of disease pathogenesis are critically needed for amyotrophic lateral sclerosis (ALS) to facilitate diagnosis and patient stratification into appropriate therapeutic trials. Proteomic studies offer significant potential to advance this, but reproducibility across laboratories is a key component toward identifying protein changes that can be translated into clinical applications.

METHODS: A combined analysis of 25 proteomic studies in human ALS biospecimens was performed to identify proteins consistently altered in ALS postmortem tissue, cerebrospinal fluid, or blood, as well as across primary regions of ALS pathology and peripheral biofluids. We consolidated these datasets into a user-friendly database "FindMND Biomarker," which is an accessible search tool that allows users to quickly determine how often, and in which biospecimen types, their proteins of interest are dysregulated in patients with ALS.

RESULTS: Our combined analysis identified 1,458 altered proteins in ALS, and revealed consistent dysregulation in mitochondrial, cytoplasmic, and RNA binding proteins in primary and later affected regions of ALS pathology. Remarkable consistency in the direction and dysregulation of chitinases and gelsolin proteins were observed across ALS biofluids. Comparisons of postmortem tissue and biofluids reinforce several known protein changes, and highlighted novel proteins of interest that may drive disease pathogenesis.

INTERPRETATION: The biospecimen type in which protein dysregulation is most consistently identified provides important insight into disease, and whether these represent potential measures of disease pathogenesis or systemic changes. By streamlining proteins by reproducibility and biospecimen type, FindMNDBiomarker is a useful resource that provides new mechanistic insights, and facilitates the prioritization of ALS-associated proteins for further validation and investigation. ANN NEUROL 2025.}, } @article {pmid40538061, year = {2025}, author = {Guo, Z and Zhang, X and Li, Y and Chen, Y and Xu, Y}, title = {Splicing to keep splicing: A feedback system for cellular homeostasis and state transition.}, journal = {Clinical and translational medicine}, volume = {15}, number = {6}, pages = {e70369}, pmid = {40538061}, issn = {2001-1326}, support = {82173292//National Natural Science Foundation of China/ ; 62171365//National Natural Science Foundation of China/ ; 62471378//National Natural Science Foundation of China/ ; 2024SF-GJHX-40//the Key Research and Development Projects of Shaanxi Province/ ; QCYRCXM-2022-209//the Key Research and Development Projects of Shaanxi Province/ ; YX6J021//Young Talent Support Plan of Xi'an Jiaotong University/ ; 2022-11//Basic-Clinical Medical Integration & Innovation Project of Xi'an Jiaotong University/ ; }, mesh = {Humans ; *Homeostasis/genetics ; *Alternative Splicing/genetics ; Feedback, Physiological ; Nonsense Mediated mRNA Decay ; }, abstract = {BACKGROUND: Alternative splicing (AS) plays a crucial role in regulating gene expression and governing proteomic diversity by generating multiple protein isoforms from a single gene. Increasing evidence has highlighted the regulation for pre-mRNA splicing of the splicing factors (SFs). This review aims to examine featured mechanisms and examples of SF regulation by AS, focusing on paradigmatic feedback loops and their biological implications.

MAIN BODY OF THE ABSTRACT: We specifically focus on the autoregulation and inter-regulation of SFs through AS machinery. These interactions give rise to a feedback system, where the negative feedback loops aid in maintaining cellular homeostasis, and the positive feedback loops play roles in triggering cellular state transitions. We examine the growing evidence highlighting the specific mechanisms employed by SFs to autoregulate their own splicing, including AS-coupled nonsense-mediated mRNA decay (AS-NMD), nuclear retention, and alternative 3'UTR regulation. We showcase the influence of AS feedback in amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and cancer. Furthermore, we discuss how master splicing factors can dominantly orchestrate splicing cascades, leading to widespread impacts in cellular processes. We also discuss how non-coding RNAs, particularly circular RNAs and microRNAs, engage in the splicing regulatory networks. Lastly, we showcase how negative and positive feedback loops can collaboratively achieve remarkable biological functions during the cell fate decision.

SHORT CONCLUSION: This review highlights the regulation of SFs by AS, providing enriched information for future investigations that aim at deciphering the intricate interplay within splicing regulatory networks.

KEY POINTS: Negative feedback of alternative splicing maintains cellular homeostasis. Positive feedback of alternative splicing triggers cellular state transitions. Alternative splicing forms integrated feedback networks with circRNAs and microRNAs to reciprocally regulate their expression and function. The coordinated interplay of distinct splicing feedback mechanisms orchestrates precise cell fate transitions. Future directions and therapeutic possibilities that could transform alternative splicing research into treatments.}, } @article {pmid40537251, year = {2025}, author = {Verde, F and Vávra, J and Dorst, J and Elmas, Z and Wiesenfarth, M and De Gobbi, A and Ratti, A and Poletti, B and Tumani, H and Weishaupt, J and Silani, V and Ticozzi, N and Otto, M and Ludolph, AC and Oeckl, P}, title = {CSF levels of the somatodendritic protein MAP2 are increased in ALS and predict shorter survival.}, journal = {Journal of neurology, neurosurgery, and psychiatry}, volume = {}, number = {}, pages = {}, doi = {10.1136/jnnp-2025-336208}, pmid = {40537251}, issn = {1468-330X}, abstract = {BACKGROUND: Previous proteomic work has identified the somatodendritic protein MAP2 as a new candidate cerebrospinal fluid (CSF) biomarker for amyotrophic lateral sclerosis (ALS).

METHODS: We measured CSF levels of MAP2 and neurofilament light chain (NFL) in a retrospective cohort of 251 patients with ALS and 108 neurological controls (NCs).

RESULTS: Patients with ALS had a higher median CSF MAP2 level compared with NCs, leading to an area under the curve (AUC) of 0.7080 (p<0.0001). They also had a higher median CSF NFL level (p<0.0001), resulting in an excellent diagnostic performance (AUC=0.9641; p<0.0001). Among patients with ALS, CSF MAP2 correlated with disease progression rate (DPR) (r=0.3099; p<0.0001) and was negatively associated with survival (HR=3.174). CSF NFL also correlated with DPR (r=0.4936; p<0.0001) and was negatively associated with survival (HR=2.759). The association of MAP2 with DPR was independent from NFL (p=0.0037). Stratifying patients based on median levels of both biomarkers resulted in significant differences in median survival times (low NFL/low MAP2, 66 months; high NFL/low MAP2 and vice versa, 35 months; high NFL/high MAP2, 26 months; p<0.0001). MAP2 was also associated with genetic status in patients with ALS, as patients with no mutations in C9ORF72 or in SOD1, as well as C9ORF72-positive ones, had higher median levels compared with NCs (p<0.0001), while patients with SOD1 mutations did not significantly differ from NCs (p>0.9999).

CONCLUSIONS: Our study shows that the somatodendritic protein MAP2 is a promising candidate CSF biomarker for ALS.}, } @article {pmid40536996, year = {2026}, author = {Yañez, IM and Torres-Cuevas, I and Corral-Debrinski, M}, title = {Neuroglobin: A promising candidate to treat neurological diseases.}, journal = {Neural regeneration research}, volume = {21}, number = {4}, pages = {1292-1303}, doi = {10.4103/NRR.NRR-D-24-01503}, pmid = {40536996}, issn = {1673-5374}, abstract = {Neurodevelopmental and neurodegenerative illnesses constitute a global health issue and a foremost economic burden since they are a large cause of incapacity and death worldwide. Altogether, the burden of neurological disorders has increased considerably over the past 30 years because of population aging. Overall, neurological diseases significantly impair cognitive and motor functions and their incidence will increase as societies age and the world's population continues to grow. Autism spectrum disorder, motor neuron disease, encephalopathy, epilepsy, stroke, ataxia, Alzheimer's disease, amyotrophic lateral sclerosis, Huntington's disease, and Parkinson's disease represent a non-exhaustive list of neurological illnesses. These affections are due to perturbations in cellular homeostasis leading to the progressive injury and death of neurons in the nervous system. Among the common features of neurological handicaps, we find protein aggregation, oxidative stress, neuroinflammation, and mitochondrial impairment in the target tissues, e.g., the brain, cerebellum, and spinal cord. The high energy requirements of neurons and their inability to produce sufficient adenosine triphosphate by glycolysis, are responsible for their dependence on functional mitochondria for their integrity. Reactive oxygen species, produced along with the respiration process within mitochondria, can lead to oxidative stress, which compromises neuronal survival. Besides having an essential role in energy production and oxidative stress, mitochondria are indispensable for an array of cellular processes, such as amino acid metabolism, iron-sulfur cluster biosynthesis, calcium homeostasis, intrinsic programmed cell death (apoptosis), and intraorganellar signaling. Despite the progress made in the last decades in the understanding of a growing number of genetic and molecular causes of central nervous diseases, therapies that are effective to diminish or halt neuronal dysfunction/death are rare. Given the genetic complexity responsible for neurological disorders, the development of neuroprotective strategies seeking to preserve mitochondrial homeostasis is a realistic challenge to lastingly diminish the harmful evolution of these pathologies and so to recover quality of life. A promising candidate is the neuroglobin, a globin superfamily member of 151 amino acids, which is found at high levels in the brain, the eye, and the cerebellum. The protein, which localizes to mitochondria, is involved in electron transfer, oxygen storage and defence against oxidative stress; hence, possessing neuroprotective properties. This review surveys up-to-date knowledge and emphasizes on existing investigations regarding neuroglobin physiological functions, which remain since its discovery in 2000 under intense debate and the possibility of using neuroglobin either by gene therapy or its direct delivery into the brain to treat neurological disorders.}, } @article {pmid40536931, year = {2025}, author = {Li, K and Chen, R and Wang, R and Fan, W and Zhao, N and Yang, Z and Yan, J}, title = {Neuroinflammation in neurodegenerative diseases: Focusing on the mediation of T lymphocytes.}, journal = {Neural regeneration research}, volume = {}, number = {}, pages = {}, doi = {10.4103/NRR.NRR-D-24-01539}, pmid = {40536931}, issn = {1673-5374}, abstract = {Neurodegenerative diseases are a group of illnesses characterized by the gradual deterioration of the central nervous system, leading to a decline in patients' cognitive, motor, and emotional abilities. Neuroinflammation plays a significant role in the progression of these diseases. However, there is limited research on therapeutic approaches to specifically target neuroinflammation. The role of T lymphocytes, which are crucial mediators of the adaptive immune response, in neurodegenerative diseases has been increasingly recognized. This review focuses on the involvement of T lymphocytes in the neuroinflammation associated with neurodegenerative diseases. The pathogenesis of neurodegenerative diseases is complex, involving multiple mechanisms and pathways that contribute to the gradual degeneration of neurons, and T cells are a key component of these processes. One of the primary factors driving neuroinflammation in neurodegenerative diseases is the infiltration of T cells and other neuroimmune cells, including microglia, astrocytes, B cells, and natural killer cells. Different subsets of CD4 + T cells, such as Th1, Th2, Th17, and regulatory T cells, can differentiate into various cell types and perform distinct roles within the neuroinflammatory environment of neurodegenerative diseases. Additionally, CD8 + T cells, which can directly regulate immune responses and kill target cells, also play several important roles in neurodegenerative diseases. Clinical trials investigating targeted T cell therapies for neurodegenerative diseases have shown that, while some patients respond positively, others may not respond as well and may even experience adverse effects. Targeting T cells precisely is challenging due to the complexity of immune responses in the central nervous system, which can lead to undesirable side effects. However, with new insights into the pathophysiology of neurodegenerative diseases, there is hope for the establishment of a solid theoretical foundation upon which innovative treatment strategies that target T cells can be developed in the future.}, } @article {pmid40536530, year = {2025}, author = {Pensato, V and Peverelli, S and Tiloca, C and Magri, S and Brusati, A and Pingue, M and Morelli, C and Dalla Bella, E and Manini, A and Tannorella, P and Doretti, A and Mandrioli, J and Terenghi, F and Prelle, A and Riva, N and Verde, F and Eleopra, R and Taroni, F and Lauria Pinter, G and Silani, V and Ticozzi, N and Gellera, C and Ratti, A}, title = {Exploring NEK1 genetic variability in Italian amyotrophic lateral sclerosis patients.}, journal = {Journal of neurology}, volume = {272}, number = {7}, pages = {469}, pmid = {40536530}, issn = {1432-1459}, support = {GR-2016-02364373//Ministero della Salute/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics ; *NIMA-Related Kinase 1/genetics ; Male ; Female ; Italy ; Middle Aged ; Aged ; Adult ; Mutation/genetics ; *Genetic Variation/genetics ; Cohort Studies ; Genetic Predisposition to Disease ; }, abstract = {BACKGROUND: Mutations in NEK1, encoding for a serine/threonine kinase which regulates several biological processes, are associated with amyotrophic lateral sclerosis (ALS).

METHODS: NEK1 was analysed by amplicon deep sequencing in a cohort of 1016 Italian sporadic and familial ALS patients previously screened for C9orf72, SOD1, TARDBP and FUS mutations.

RESULTS: We identified 28 rare NEK1 variants in 29 patients (2.85%) of whom 20/782 were sporadic (2.5%), 6/107 familial (5%) and 3/127 of unknown aetiology (2.3%). Variants were classified as pathogenic (P; n = 1), likely pathogenic (LP; n = 6 in 7 patients) and of unknown significance (VUS; n = 21) according the American College of Medical Genetics and Genomics criteria. Notably, 64% of the identified variants (18/28, including 4 LP and 14 VUS) were novel. Among the 29 patients with rare NEK1 variants, 7 (of whom 5 were familial cases) had additional variants in one of the four main ALS causative genes. Moreover, 23 patients carried the already reported NEK1 p.Arg261His risk variant (VUS) alone or in addition to SOD1 mutations (n = 1) or C9orf72 repeat expansion (n = 2) and to the NEK1 p.Asp128Val variant (n = 1). Genotype-phenotype correlation analysis showed no significant differences in age at onset or survival in NEK1 variant carriers, independently on the variant type. No flail arm phenotype, but atypical features, including sensory symptoms, were present in NEK1 carriers.

CONCLUSION: Our study further expands NEK1 genetic variability by identifying novel rare variants and confirming ALS oligogenic nature since 19.6% of NEK1 patients also carried mutations in one of the four main ALS-associated genes.}, } @article {pmid40535632, year = {2025}, author = {Tang, X and Wang, C and Tian, S and Wen, H and Zhang, H}, title = {Acupuncture for neurodegenerative diseases: mechanisms, efficacy, and future research directions.}, journal = {American journal of translational research}, volume = {17}, number = {5}, pages = {3703-3717}, pmid = {40535632}, issn = {1943-8141}, abstract = {In recent years, acupuncture has shown good therapeutic efficacy in treating neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and multiple sclerosis. Studies have demonstrated that acupuncture alleviates symptoms primarily by suppressing neuroinflammation, enhancing autophagy, improving synaptic plasticity, and optimizing mitochondrial function. As molecular research advances, the underlying mechanisms of acupuncture in these conditions have become increasingly clear. This review summarizes recent progress in understanding the efficacy and molecular mechanisms of acupuncture in neurodegenerative diseases, providing a theoretical support for its clinical application.}, } @article {pmid40534726, year = {2025}, author = {Kissling, WD and Mulder, W and Wang, J and Shi, Y}, title = {Data of vegetation structure metrics retrieved from airborne laser scanning surveys for European demonstration sites.}, journal = {Data in brief}, volume = {60}, number = {}, pages = {111548}, pmid = {40534726}, issn = {2352-3409}, abstract = {This dataset provides a standardized collection of rasterized Light Detection And Ranging (LiDAR) metrics in GeoTIFF format, derived from country-wide airborne laser scanning (ALS) data across seven demonstration sites in five European countries: Mols Bjerge National Park (Denmark), Reserve Naturelle Nationale du Bagnas (France), Oostvaardersplassen (Netherlands), Salisbury Plain (United Kingdom), Knepp Estate (United Kingdom), Monks Wood (United Kingdom), and the island of Comino (Malta). The sites range in areal size from 0.08 km[2] to 54 km[2] and include habitat types such as forests, broadleaf and conifer woodlands, small plantations, dry and wet grasslands, marshes, reedbeds, arable fields, farmland, scrublands and mediterranean garigue. A total of 35 LiDAR metrics were calculated, of which 28 represent vegetation structural attributes. These include vegetation height (seven metrics), vegetation cover (fourteen metrics), and vegetation vertical variability (seven metrics). Additionally, seven metrics describe point density (one metric), eigenvalues (three metrics), and normal vectors (three metrics). The rasterized LiDAR metrics have a spatial resolution of 10 m, with coverage and extent defined by shapefiles corresponding to each demonstration site. The raw ALS point clouds were clipped to the site boundaries and processed with the 'Laserfarm' workflow, a standardized computational workflow that includes modular pipelines for re-tiling, normalization, feature extraction, and rasterization. Laserfarm employs the feature extraction module of the open-source 'Laserchicken' software to compute the LiDAR metrics. The workflow was implemented using the IT services of the Dutch national facility for information and communication technology, SURF. The clipped LiDAR point clouds are available through a public repository, except for the LiDAR point clouds from Comino, Malta, which are not publicly available. The 35 rasterized LiDAR metrics (GeoTIFF files, 10 m resolution) from all sites, including Comino, as well as the corresponding site boundary shapefiles (geospatial vector format), are provided in a Zenodo repository. Additionally, the Jupyter Notebooks with Python code for executing the Laserfarm workflow are available to facilitate reproducibility and further computational applications. Users should note that the rasterized LiDAR metrics may contain zero or NA values, particularly over water surfaces, with the pulse penetration ratio metric potentially indicating false high vegetation cover over water. Users may reclassify or mask areas with zero values accordingly. Some pixels exhibit abnormal vegetation height values, which can be filtered before analysis. Certain striping patterns, likely resulting from overlapping flight lines and increased point density, are present in some metrics, though their overall impact appears minimal. This dataset enables diverse applications, including canopy height measurements, mapping of hedgerows, treelines, and forest patches, as well as characterizing vegetation density, vertical stratification, and habitat openness. It supports landscape-scale habitat analysis and contributes to the standardization of vegetation metrics from ALS data for site-specific ecological monitoring (e.g., Natura 2000). Moreover, the dataset demonstrates the automated execution of LiDAR data processing workflows, which is crucial for establishing a transnational and multi-site biodiversity and ecosystem observation network.}, } @article {pmid40534528, year = {2025}, author = {Ertural, B and Çiçek, BN and Kurnaz, IA}, title = {RNA Therapeutics: Focus on Antisense Oligonucleotides in the Nervous System.}, journal = {Biomolecules & therapeutics}, volume = {33}, number = {4}, pages = {572-581}, pmid = {40534528}, issn = {1976-9148}, abstract = {RNA therapeutics represent a disruptive technology that has transformed drug discovery and manufacturing, gaining significant prominence during the COVID-19 pandemic. RNA therapeutics encompass diverse molecules like antisense oligonucleotides (ASOs), small interfering RNAs (siRNAs), microRNAs (miRNAs), RNA aptamers, and messenger RNAs (mRNAs), which can function through different mechanisms. RNA therapeutics are increasingly used to treat various diseases, including neurological disorders. For example, ASO therapies such as nusinersen for spinal muscular atrophy and eteplirsen for Duchenne muscular dystrophy are successful applications of RNA-based treatment. Emerging ASO treatments for Huntington's disease and amyotrophic lateral sclerosis are also promising, with ongoing clinical trials demonstrating significant reductions in disease-associated proteins. Still, delivery of these molecules remains a pivotal challenge in RNA therapeutics, especially for ASOs in penetrating the blood-brain barrier to target neurological disorders effectively. Nanoparticle-based formulations have emerged as leading strategies to enhance RNA stability, reduce immunogenicity, and improve cellular uptake. Despite these advances, significant hurdles remain, including optimizing pharmacokinetics, minimizing off-target effects, and ensuring sustained therapeutic efficacy. Regulatory frameworks are evolving to accommodate the unique challenges of RNA-based therapies, including ASOs with efforts underway to establish comprehensive guidelines for RNA therapeutics, yet there are also sustainable manufacturing issues that need to be considered for long-term feasibility. By addressing these challenges, RNA therapeutics hold immense potential to revolutionize treatment paradigms for neurological disorders. Looking forward, the future of RNA therapeutics in neurology appears promising but requires continued interdisciplinary collaboration and technological innovation.}, } @article {pmid40533880, year = {2025}, author = {Liu, W and Wang, S and Zhang, T and Zhu, H and Chang, N and Zhang, L and Hu, Z}, title = {A Review of Preparation of Low-Carbon Cementitious Materials from Chemically Activated Red Mud: Synergy, Hydration Mechanism, Rheological Properties and Applications.}, journal = {Langmuir : the ACS journal of surfaces and colloids}, volume = {41}, number = {25}, pages = {15735-15751}, doi = {10.1021/acs.langmuir.5c01088}, pmid = {40533880}, issn = {1520-5827}, abstract = {Red mud, a byproduct of the alumina refining process, is generated at a rate of 1-2.5 tonnes per tonne of alumina produced. In 2022, China's alumina production totaled 77.475 million tonnes, contributing over 4 billion tonnes of accumulated red mud, which is the third-largest industrial solid waste in the country. Red mud's high alkalinity and presence of toxic elements pose environmental challenges, particularly in terms of disposal. This review provides a comprehensive examination of red mud-based cementitious materials, focusing on their preparation, properties, and environmental impact. By combining red mud with high-calcium and silica-aluminum solid wastes and enhancing its reactivity through mechanical grinding or thermal activation, red mud's cementitious activity can be significantly improved. Optimized compositions, with a Ca/Si ratio of 2.05 and Al/S ratio of 0.70, have achieved compressive strengths of up to 63.9 MPa at 28 day. Durability studies highlight the material's resistance to chloride ion penetration and sulfate attack, with reduced permeability enhancing long-term performance. Additionally, environmental assessments confirm that stabilization and solidification techniques effectively mitigate heavy metal leaching, ensuring compliance with EPA standards. Despite these advancements, challenges remain in optimizing red mud activation processes, improving rheological properties, and reducing production costs. Future research should focus on refining activation methods, enhancing hydration mechanisms, and developing scalable industrial applications. By addressing these gaps, red mud-based cementitious materials can become a sustainable solution for eco-friendly construction, supporting global efforts to repurpose industrial byproducts into low-carbon, durable building materials.}, } @article {pmid40531663, year = {2025}, author = {Ralston, CY and Gupta, S and Del Mundo, JT and Soe, AC and Russell, B and Rad, B and Tyler, J and Paul, S and Kahan, DN and Kristensen, LG and Subramanian, S and Kidd, S and Burnett, K and Sankaran, B and Classen, S and Prigozhin, DM and Taylor, JR and Dickert, JM and Royal, KB and Rozales, A and Ortega, SL and Allaire, M and Nix, JC and Hura, GL and Holton, JM and Hammel, M and Adams, PD}, title = {ALS-ENABLE: creating synergy and opportunity at the Advanced Light Source synchrotron structural biology beamlines.}, journal = {Journal of synchrotron radiation}, volume = {32}, number = {Pt 4}, pages = {1059-1067}, pmid = {40531663}, issn = {1600-5775}, support = {P30 GM124169/GM/NIGMS NIH HHS/United States ; GM126218//National Institutes of Health, National Institute of General Medical Sciences/ ; GM124169//National Institutes of Health, National Institute of General Medical Sciences/ ; DE-AC02-05CH1123//US Department of Energy, Office of Science/ ; R01 GM126218/GM/NIGMS NIH HHS/United States ; }, mesh = {*Synchrotrons/instrumentation ; Scattering, Small Angle ; Crystallography, X-Ray/instrumentation ; Mass Spectrometry ; X-Ray Diffraction ; }, abstract = {ALS-ENABLE is an integrated NIH P30 resource at the Advanced Light Source synchrotron at Lawrence Berkeley National Laboratory in Berkeley, California, USA. The resource provides a single portal to the combined mature structural biology technologies of macromolecular crystallography, small-angle X-ray scattering and X-ray footprinting mass spectrometry, and includes beamlines 2.0.1, 3.3.1, 4.2.2, 5.0.1, 5.0.2, 5.0.3, 8.2.1, 8.2.2, 8.3.1 and 12.3.1. This paper describes the organizational structure and the technologies of ALS-ENABLE. A case study showcasing the main technologies of the resource applied to the characterization of the SpyCatcher-SpyTag protein system is presented.}, } @article {pmid40531650, year = {2025}, author = {Zeng, W and Peng, Z and Chen, Y and Du, S}, title = {Multi-Scale Temporal Analysis with a Dual-Branch Attention Network for Interpretable Gait-Based Classification of Neurodegenerative Diseases.}, journal = {IEEE journal of biomedical and health informatics}, volume = {PP}, number = {}, pages = {}, doi = {10.1109/JBHI.2025.3580944}, pmid = {40531650}, issn = {2168-2208}, abstract = {The accurate diagnosis of neurodegenerative diseases (NDDs), such as Amyotrophic Lateral Sclerosis (ALS), Huntington's Disease (HD), and Parkinson's Disease (PD), remains a clinical challenge due to the complexity and subtlety of gait abnormalities. This paper proposes the Dual-Branch Attention-Enhanced Residual Network (DAERN), a novel deep learning architecture that integrates Dilated Causal Convolutions (DCCBlock) for local gait pattern extraction and Multi-Head Self-Attention (MHSA) for long-range dependency modeling. A CrossAttention Fusion module enhances feature integration, while SHapley Additive exPlanations (SHAP) and Integrated Gradients (IG) improve interpretability, providing clinically relevant insights into gait-based NDD classification. Uniform Manifold Approximation and Projection (UMAP) visualizations reveal well-separated clusters corresponding to distinct NDDs categories, demonstrating the model's ability to capture discriminative features. Comprehensive ablation studies validate the contributions of model components and preprocessing strategies, highlighting the significance of each in achieving state-of-the-art classification performance. Experimental evaluations on the Gait in Neurodegenerative Disease (GaitNDD) dataset demonstrate that DAERN achieves an accuracy of 99.64%, an F1-score of 99.65%, and an AUC of 0.9997, significantly outperforming conventional deep learning and machine learning baselines. These findings suggest that DAERN could be a valuable and interpretable tool for clinical gait assessment, aiding in early-stage monitoring and automated screening of NDDs, with potential applications in real-time wearable sensor-based gait analysis.}, } @article {pmid40531486, year = {2025}, author = {Berry, JD and Maragakis, N and Paganoni, S}, title = {CNM-Au8 in Amyotrophic Lateral Sclerosis-Reply.}, journal = {JAMA}, volume = {334}, number = {3}, pages = {278}, doi = {10.1001/jama.2025.5825}, pmid = {40531486}, issn = {1538-3598}, } @article {pmid40531483, year = {2025}, author = {Endo, M and Kami, M}, title = {CNM-Au8 in Amyotrophic Lateral Sclerosis.}, journal = {JAMA}, volume = {334}, number = {3}, pages = {277-278}, doi = {10.1001/jama.2025.5822}, pmid = {40531483}, issn = {1538-3598}, } @article {pmid40530462, year = {2025}, author = {Raymond, J and Oskarsson, B and Larson, T and Mohidul, S and Horton, DK and Mehta, P}, title = {Place of Death in Patients with Motor Neuron Disease and the Association with Comorbidities During the Coronavirus Disease 2019 Pandemic: A Population-Based Analysis.}, journal = {Journal of palliative care}, volume = {}, number = {}, pages = {8258597251349627}, doi = {10.1177/08258597251349627}, pmid = {40530462}, issn = {2369-5293}, abstract = {ObjectiveMotor neuron disease (MND) is a progressive neurological disorder with no known cure that damages motor neurons. The purpose of this analysis is to examine the place of death for MND patients in the United States during the coronavirus disease 2019 (COVID-19) pandemic and to investigate the extent of specific comorbidities.MethodsWe obtained death certificate and associated comorbidities data for all U.S. MND deaths from 2018 to 2021 and conducted a population-based cross-sectional analysis of the deaths pre-COVID-19 (2018-2019) and during COVID-19 (2020-2021). We hypothesized that place of death and comorbidities associated with place of death for MND patients in the United States were altered during the COVID-19 pandemic in comparison to the 2 years period before the pandemic.ResultsWe analyzed 30 066 MND deaths (14 562 pre-COVID-19 and 15 504 during COVID-19) aged 20 years and older. During COVID-19, MND deaths at home increased (54.4% vs 45.5% pre-COVID). Hispanic individuals had an increased likelihood of dying at home compared to a nursing home or hospice (OR = 1.57, 95%CI: 1.22-2.02), but a decreased likelihood compared to a hospital (OR = 0.61, 95% CI: 0.51-0.72). Among the top comorbidities listed, there was a 27.8% increase in diabetes mellitus and a 20.2% increase in essential hypertension during COVID-19. During COVID-19, diabetes mellitus was more commonly reported as a comorbidity for deaths occurring in hospitals (OR = 1.40, 95%CI: 1.03-1.89) or at home (OR = 1.26, 95%CI: 1.03-1.55), while essential hypertension was more commonly reported with deaths at home (OR = 1.17, 95%CI: 1.01-1.36).ConclusionOur analysis showed an increase in at-home MND deaths as well as certain comorbidities during the COVID-19 pandemic, suggesting MND patients had a higher likelihood of death from non-COVID-19 comorbidities.}, } @article {pmid40529392, year = {2025}, author = {Pfaff, AL and Kõks, S}, title = {Retrotransposition-competent L1s are increased in the genomes of individuals with amyotrophic lateral sclerosis.}, journal = {Experimental biology and medicine (Maywood, N.J.)}, volume = {250}, number = {}, pages = {10575}, pmid = {40529392}, issn = {1535-3699}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics ; *Long Interspersed Nucleotide Elements/genetics ; *Genome, Human ; Female ; Male ; Middle Aged ; Genetic Predisposition to Disease ; Retroelements ; }, abstract = {An individual's genetics contributes to their risk of developing amyotrophic lateral sclerosis (ALS); however, there is still a large proportion of the heritability of ALS to be understood. Part of this missing heritability may lie in complex variants, such as the long interspersed element 1 (L1) retrotransposon, which have yet to be evaluated. The majority of L1 insertions in the human genome are no longer able to retrotranspose, but to date 279 retrotransposition-competent (RC) L1s have been reported. Many RC-L1s are polymorphic for their presence/absence; therefore, each individual will have a different number and complement of RC-L1s. These elements have been hypothesized to be involved in disease processes by multiple mechanisms such as somatic mutation by retrotransposition, the triggering of neuroinflammation and DNA damage. We hypothesize that L1s may influence disease development either through their effects on endogenous genes or through the properties that enable them to retrotranspose. Whole genome sequencing data from the New York Genome Center ALS consortium were used to characterize L1 variation identifying 2,803 polymorphic L1 elements and association analysis was performed in European individuals (ALS/ALS with other neurological disorder (ALSND) n = 2,653, controls n = 320). There were no individual L1 elements associated with disease, but we did identify a significant increase in the number of RC-L1s in ALS/ALSND genomes (p = 0.01) and the presence of ≥46 RC-L1s showed the most significant association (OR = 1.09 (1.02-1.16), p = 0.01) with disease. Analysis of individual L1s and their association with age at onset and survival identified one L1 whose presence was significantly associated with a lower age at onset (52.7 years) compared to homozygous absent individuals (59.2 years) (padj = 0.009). Our study has identified novel genetic factors for both disease risk and age at onset in ALS providing further evidence for the role of L1 retrotransposons in neurodegenerative diseases.}, } @article {pmid40528459, year = {2025}, author = {Yang, M and Zhang, A and Chen, M and Cao, J}, title = {Advances in Circulating Biomarkers for Neurodegenerative Diseases, Traumatic Brain Injuries, and Central Nervous System Tumors.}, journal = {Annals of laboratory medicine}, volume = {45}, number = {4}, pages = {381-390}, pmid = {40528459}, issn = {2234-3814}, mesh = {Humans ; *Brain Injuries, Traumatic/diagnosis/blood ; *Neurodegenerative Diseases/diagnosis/blood ; *Biomarkers/blood/cerebrospinal fluid ; *Central Nervous System Neoplasms/diagnosis/blood ; Enzyme-Linked Immunosorbent Assay ; tau Proteins/blood/cerebrospinal fluid ; }, abstract = {Neurological disorders, including neurodegenerative diseases, traumatic brain injuries (TBI), and central nervous system (CNS) tumors, are complex conditions that significantly impact patients globally. Timely diagnosis and monitoring are critical for improving outcomes, driving the need for reliable biomarkers. Specifically, biomarkers detectable in cerebrospinal fluid (CSF) and blood offer important insights into disease presence and progression. This review explores the evolution of circulating blood biomarkers for neurodegenerative diseases, TBI, and CNS tumors, highlighting advanced detection technologies from enzyme-linked immunosorbent assays (ELISAs) to electrochemiluminescence (ECL) assays, single-molecule arrays (Simoa), and mass spectrometry. Advanced technologies with enhanced sensitivity and specificity, particularly in detecting low-abundance analytes, facilitate the investigation of CSF biomarkers for various neurological disorders. We also describe the progress in blood-based biomarkers for , emerging as less invasive alternatives to CSF sampling. Clinically, the implementation of Alzheimer's disease (AD) blood biomarkers Aβ42/Aβ40 ratio and Apolipoprotein E isoform-specific peptide can aid the diagnosis, while p-tau181 and p-tau217 differentiates AD dementia from non-AD neurodegenerative diseases. Blood glial fibrillary acidic protein and ubiquitin C-terminal hydrolase-L1 are used in ruling out mild TBI. Despite these innovations, challenges remain, including assay standardization, sensitivity/specificity trade-offs, and the requirement for longitudinal studies to understand biomarker utility over time. Future research should focus on addressing these challenges to fully realize the potential of blood-based biomarkers in neurological disorder diagnostics and patient care.}, } @article {pmid40528238, year = {2025}, author = {Huang, X and Zhang, Z and Chen, L and Yang, S and Liu, X and Bi, J and Zhang, Z and Wang, Y and Wei, N and Zhu, W and Chen, N and Hua, L and Li, Y and Wang, Y and Jing, J and Pan, H}, title = {Diagnostic value of the motor band sign in amyotrophic lateral sclerosis: a 7T magnetic resonance imaging study.}, journal = {Translational neurodegeneration}, volume = {14}, number = {1}, pages = {30}, pmid = {40528238}, issn = {2047-9158}, } @article {pmid40527647, year = {2025}, author = {Thijs, Z and Calzada, A and Sosa, M and Dumican, M}, title = {The Association Between Bilingualism and Voice Quality in Spanish-English Bilingual Speakers: A Systematic Review.}, journal = {Journal of voice : official journal of the Voice Foundation}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jvoice.2025.05.027}, pmid = {40527647}, issn = {1873-4588}, abstract = {OBJECTIVE/HYPOTHESIS: The vast majority of the global population speaks more than one language. In the United States, Spanish-English bilingual speakers are the largest bilingual group. Yet, the potential effect of being bilingual, specifically a Spanish-English speaker, on voice quality is poorly understood. The current study consequently set out to systematically review the literature on the association between being a Spanish-English bilingual speaker and voice quality.

STUDY DESIGN: Systematic review.

METHODS: A systematic review of association was conducted using Moola et al's guidelines. A search string was developed and run in May 2024 across three databases: MEDLINE (via PubMed), CINAHL via EBSCOhost, and Scopus. After duplicate removal, title, and abstract screening, full-text screening was performed, and peer-reviewed articles considering voice quality measures in Spanish-English bilingual speakers were included. Data were extracted and presented in table format, and the quality of the articles was assessed using the Checklist for Analytical Cross-Sectional Studies.

RESULTS: In total, 685 records were retrieved, with 485 remaining after duplicate removal. After title and abstract screening, 25 full texts were screened, including 8 articles in the review. Five studies included acoustic measures describing voice quality, with only three including auditory-perceptual analysis. The most commonly considered vocal trait in Spanish-English bilinguals was vocal fry, with the included studies pointing to increased vocal fry use when speaking English.

CONCLUSIONS: Only a few articles discuss potential vocal changes in Spanish-English bilinguals. Further research is needed to elucidate any potential vocal changes related to being a bilingual speaker, as the current small number of studies and mixed findings make drawing conclusions difficult. More standardization across voice and language assessment could be beneficial.}, } @article {pmid40527529, year = {2025}, author = {Cassidy-Seyoum, SA and Adhikari, B and Chheng, K and Chanpheakdey, P and Meershoek, A and Hsiang, MS and von Seidlein, L and Tripura, R and Ley, B and Price, RN and Dysoley, L and Thriemer, K and Engel, N}, title = {Acceptability and feasibility of glucose-6-phosphate dehydrogenase (G6PD) testing using SD Biosensor by village malaria workers in Cambodia: a qualitative study.}, journal = {BMJ global health}, volume = {10}, number = {6}, pages = {}, pmid = {40527529}, issn = {2059-7908}, mesh = {Humans ; Cambodia ; Qualitative Research ; Feasibility Studies ; *Glucosephosphate Dehydrogenase/blood/analysis ; Female ; *Community Health Workers ; *Biosensing Techniques/methods ; Focus Groups ; Male ; *Glucosephosphate Dehydrogenase Deficiency/diagnosis ; *Patient Acceptance of Health Care/statistics & numerical data ; *Malaria, Vivax/drug therapy ; Adult ; Interviews as Topic ; Point-of-Care Testing ; Middle Aged ; Malaria ; Primaquine/therapeutic use ; }, abstract = {INTRODUCTION: Plasmodium vivax is the predominant cause of malaria in the Greater Mekong Subregion. To ensure safe treatment with primaquine, point-of-care glucose-6-phosphate dehydrogenase (G6PD) testing was rolled out in Cambodia at the health facility level, although most malaria patients are diagnosed in the community. The current study aims to explore the acceptability and feasibility of implementing community-level G6PD testing in Cambodia.

METHODS: Semistructured interviews and focus group discussions (FGD) were conducted. Across eight study sites in three provinces, 142 respondents, including policymakers, programme officers, healthcare providers and patients, participated in 67 interviews and 19 FGDs in 2022 and 2023. Data were analysed thematically using an adapted framework derived from Bowen et al's feasibility framework and Sekhon et al's acceptability framework.

RESULTS: All stakeholders attributed value to the intervention. Acknowledging an intervention's different values can help discern policy implications for an intervention's successful implementation. Building and maintaining confidence in the device, end users, infrastructure and health systems were found to be key elements of acceptability. In general, health centre workers and village malaria workers (VMWs) had confidence that VMWs could conduct the test and administer treatment given appropriate initial training, monthly refresher training and the test's repeated use. More is required to build policymakers' confidence, while some implementation challenges, including the test's regulatory approval, stability above 30°C and cost, need to be overcome.

CONCLUSION: Implementation of G6PD testing at the community level in Cambodia is an acceptable and potentially feasible option but requires addressing implementation challenges and building and maintaining confidence among stakeholders.}, } @article {pmid40527446, year = {2025}, author = {Zhang, Z and Guo, X and Liu, Y and Ke, P and Meng, Y and Gu, J and Hu, L and Yuan, Z and Duan, R and Luo, J and Xiao, F}, title = {PKM2 alleviates mitochondrial oxidative stress and neuronal apoptosis through metabolic and non-metabolic pathways to protect SOD1[G93A] mice.}, journal = {Free radical biology & medicine}, volume = {238}, number = {}, pages = {1-16}, doi = {10.1016/j.freeradbiomed.2025.06.012}, pmid = {40527446}, issn = {1873-4596}, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by selective motor neuron death. Dysregulated energy metabolism is implicated in ALS pathogenesis, yet the role of pyruvate kinase M2 (PKM2), a key glycolytic enzyme, remains elusive. Here, we demonstrated that PKM2 expression was upregulated in the spinal neurons of SOD1[G93A] mice during early stages of disease. Pharmacological inhibition of PKM2 with compound 3k (C3k) shortened survival times, exacerbated motor deficits, and amplified mitochondrial oxidative stress and neuronal apoptosis in mice with ALS. Mechanistically, PKM2 mitigated mitochondrial dysfunction via its enzymatic activity, promoting lactate metabolism to reduce reactive oxygen species (ROS) accumulation. Concurrently, nuclear PKM2 directly bound to the Nrf2 promoter, enhancing Nrf2 transcription to strengthen antioxidant defenses. Our findings unveil PKM2 as a multifunctional neuroprotectant in ALS, offering novel therapeutic directions through metabolic and transcriptional modulation.}, } @article {pmid40525139, year = {2025}, author = {Abou Izzeddine, N and Ahmad, K and Bacha, C and Jabbour, M and Najjar, M and Salhab, S and Ghadieh, HE and Kanaan, A and Azar, S and Khattar, ZA and Harb, F}, title = {The microbial guardians: Unveiling the role of gut microbiota in shaping neurodegenerative disease.}, journal = {IBRO neuroscience reports}, volume = {19}, number = {}, pages = {17-37}, pmid = {40525139}, issn = {2667-2421}, abstract = {The gut microbiota, a complex community of microorganisms residing in the digestive tract, plays a pivotal role in human health. Recent studies have highlighted its significant impact on neurodegenerative diseases, conditions that pose profound challenges to affected individuals and society at large. This review explores the intricate relationship between gut microbiota and the progression of neurodegenerative disorders, such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and Amyotrophic Lateral Sclerosis. We delve into the dynamic ecosystem of gut microbiota, examining factors influencing its composition and the bidirectional communication established via the gut-brain axis. Emerging evidence suggests that gut microbiota can modulate neurodegenerative disease progression through mechanisms including inflammatory responses, production of neuroactive substances, and regulation of neurotransmitters. Furthermore, we discuss the potential therapeutic implications of targeting gut microbiota with probiotics, prebiotics, and postbiotics. While promising, these interventions face challenges and limitations that must be addressed through ongoing research. Understanding the role of gut microbiota in neurodegenerative diseases is crucial for developing innovative therapeutic strategies and improving patient outcomes.}, } @article {pmid40524150, year = {2025}, author = {Cozzi, M and Tedesco, B and Ferrari, V and Chierichetti, M and Pramaggiore, P and Cornaggia, L and Magdalena, R and Brodnanova, M and Mohamed, A and Milioto, C and Piccolella, M and Galbiati, M and Rusmini, P and Crippa, V and Gellera, C and Magri, S and Taroni, F and Cristofani, R and Poletti, A}, title = {One gene, many phenotypes: the role of KIF5A in neurodegenerative and neurodevelopmental diseases.}, journal = {Cell communication and signaling : CCS}, volume = {23}, number = {1}, pages = {287}, pmid = {40524150}, issn = {1478-811X}, support = {PRIN- Progetti di ricerca di interesse nazionale - bando 2022, PNRR finanziato dall'Unione europea- Next Generation EU, componente M4C2, investimento 1.1 n. P20225R4Y5//Ministero dell'Università e della Ricerca/ ; PRIN-Progetti di ricerca di interesse nazionale n. 2022EFLFL8//Ministero dell'Università e della Ricerca/ ; 23236//AFM-Téléthon/ ; 739510//European Network for Rare Neurological Disorders/ ; piano di sviluppo della ricerca (PSR) UNIMI//Università degli Studi di Milano/ ; R21 AR080407/AR/NIAMS NIH HHS/United States ; Travelling Fellowship n. JCSTF2205742//Company of Biologists/ ; R21AR080407/AR/NIAMS NIH HHS/United States ; RF-2018-12367768//Ministero della Salute/ ; . 2021-1544//Fondazione Cariplo/ ; Scientific Exchange Grant n. 9643//European Molecular Biology Organization/ ; 2025 grant//CureHSPB8,USA/ ; PRIN-Progetti di ricerca di interesse nazionale n. 2020PBS5MJ//Ministero dell'Università e della Ricerca/ ; CP 20/2018 (Care4NeuroRare)//Fondazione Regionale per la Ricerca Biomedica/ ; 2020 grant//Kennedy's Disease Association/ ; 2018 grant//Kennedy's Disease Association/ ; }, abstract = {UNLABELLED: Kinesin family member 5 A (KIF5A) is a neuron-specific molecular motor involved in anterograde transport. KIF5A mediates a wide range of trafficking processes that are only partially shared with the other members of the KIF5 family. Since 2002, several disease-causing mutations have been found in the KIF5A gene and a link between the specific domain in the encoded protein affected by mutations and the associated phenotype has become evident. Point mutations targeting KIF5A motor and stalk domains, that are expected to impair KIF5A motility, mainly associate with spastic paraplegia type 10 (SPG10) and axonal Charcot-Marie-Tooth (CMT) disease. Oppositely, translational frameshifts causing the elongation of KIF5A tail enhance KIF5A migration towards cell periphery, induce kinesin aggregation, and are linked to amyotrophic lateral sclerosis (ALS) or neonatal intractable myoclonus (NEIMY). This review correlates KIF5A structure and roles in neuronal trafficking with its involvement in the above-mentioned neurodegenerative and neurodevelopmental conditions.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12964-025-02277-x.}, } @article {pmid40524084, year = {2025}, author = {Ticozzi, N and Padovani, A and Filosto, M and , }, title = {ALS global day 2025: research and clinical advances.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {46}, number = {8}, pages = {3359-3361}, pmid = {40524084}, issn = {1590-3478}, } @article {pmid40524081, year = {2025}, author = {Uygun, Ö and Unkun, R and Asan, F and Gündüz, A}, title = {Facial onset sensory-motor neuronopathy: diagnostic challenges and insights from a case report.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {}, number = {}, pages = {}, pmid = {40524081}, issn = {1590-3478}, } @article {pmid40523602, year = {2025}, author = {Horikawa, I and Yamada, L and Harris, BT and Harris, CC}, title = {Δ133p53α-mediated inhibition of astrocyte senescence and neurotoxicity as a possible therapeutic approach for neurodegenerative diseases.}, journal = {Neuroscience}, volume = {580}, number = {}, pages = {54-61}, pmid = {40523602}, issn = {1873-7544}, support = {ZIA BC011496/ImNIH/Intramural NIH HHS/United States ; }, mesh = {Humans ; *Astrocytes/metabolism/drug effects/pathology ; *Cellular Senescence/physiology ; *Tumor Suppressor Protein p53/metabolism ; *Neurodegenerative Diseases/metabolism/therapy ; Animals ; Protein Isoforms/metabolism ; }, abstract = {Non-neuronal glial cells in the brain, such as astrocytes, play essential roles in maintaining the functional integrity of neuronal cells. A growing body of evidence suggests that cellular senescence of astrocytes, characterized by loss of proliferative potential and secretion of neurotoxic cytokines, makes significant contribution to neurotoxicity in Alzheimer's disease and a wide range of other neurodegenerative diseases. This review discusses the beneficial effects of Δ133p53α, a natural p53 protein isoform that inhibits p53-mediated cellular senescence, thereby protecting astrocytes from senescence, highlights its potential as a therapeutic target, and underscores the need for continued research in this area. Both in senescent human astrocytes in culture, whether induced by replicative exhaustion, irradiation or exposure to amyloid-β, and in brain tissues with increased senescent astrocytes from patients with Alzheimer's disease, the expression levels of endogenous Δ133p53α protein were consistently and significantly reduced. The lentiviral vector-driven expression of Δ133p53α protected cultured human astrocytes from cellular senescence and neurotoxic secretory phenotype, leading to their cellular reprogramming to a neuroprotective state associated with neurotrophic growth factors. We thus propose that Δ133p53α is worth testing as a therapeutic target that can be enhanced in a wide range of neurodegenerative diseases with accumulated senescent astrocytes, including Alzheimer's disease, amyotrophic lateral sclerosis, Parkinson's disease, and chronic traumatic encephalopathy due to traumatic brain injury. We hypothesize that a Δ133p53α-mediated cellular reprogramming approach and a senolytic or senomorphic approach, both targeting non-neuronal cells, may be complementary with each other, and may cooperate with neuron-protecting or amyloid-β-targeting therapies currently in use.}, } @article {pmid40523537, year = {2025}, author = {Risby-Jones, G and Marallag, J and Jagaraj, CJ and Atkin, JD and Walker, AK and Woodruff, TM and Lee, JD and Fung, JN}, title = {IL-6 trans-signalling is elevated in ALS models and drives TDP-43 induced inflammatory responses in microglia.}, journal = {Brain, behavior, and immunity}, volume = {129}, number = {}, pages = {296-304}, doi = {10.1016/j.bbi.2025.06.021}, pmid = {40523537}, issn = {1090-2139}, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by chronic inflammation in both the central nervous system (CNS) and peripheral tissues. Interleukin-6 (IL-6) has been implicated in ALS pathology; however, IL-6 exhibits both anti-inflammatory and pro-inflammatory functions. Notably, IL-6 trans-signalling possesses pro-inflammatory properties and is emerging as a key contributor to neuroinflammation during neurodegeneration. In this study, we aimed to characterize the expression of the IL-6 trans-signalling pathway in ALS mouse models and investigate its role in ALS protein aggregate-mediated inflammation in microglia and peripheral immune cells. Our results revealed that the protein expression level of a key IL-6 trans-signalling component, soluble IL-6 receptor (sIL-6R), was significantly increased in the spinal cord and tibialis anterior (TA) muscles of both SOD1[G93A] and rNLS8 TDP-43 transgenic mice. Additionally, using mouse primary microglia, human monocyte-derived microglia-like cells (MDMi), and blood peripheral immune cells, we demonstrated that recombinant TDP-43 protein elicits robust pro-inflammatory cytokine responses, including IL-6, TNF-α, IL-23, and MCP-1. These responses were attenuated when treated with a specific IL-6 trans-signalling inhibitor, sgp130Fc. Our findings suggest that the TDP-43-induced inflammatory response is, in part, IL-6 trans-signalling-dependent and highlight the role of IL-6 trans-signalling as a potential driver of chronic inflammation contributing to ALS pathology. These results support IL-6 trans-signalling as a promising therapeutic target for mitigating inflammation and slowing disease progression. Future research should explore the broader implications of modulating IL-6 trans-signalling in ALS.}, } @article {pmid40522761, year = {2026}, author = {Fan, T and Peng, J and Liang, H and Chen, W and Wang, J and Xu, R}, title = {Potential common pathogenesis of several neurodegenerative diseases.}, journal = {Neural regeneration research}, volume = {21}, number = {3}, pages = {972-988}, pmid = {40522761}, issn = {1673-5374}, abstract = {With the gradual advancement of research methods and technologies, various biological processes have been identified as playing roles in the pathogenesis of neurodegenerative diseases. However, current descriptions of these biological processes do not fully explain the onset, progression, and development of these conditions. Therefore, exploration of the pathogenesis of neurodegenerative diseases remains a valuable area of research. This review summarizes the potential common pathogeneses of Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease, frontotemporal lobar dementia, and Lewy body disease. Research findings have indicated that several common biological processes, including aging, genetic factors, progressive neuronal dysfunction, neuronal death and apoptosis, protein misfolding and aggregation, neuroinflammation, mitochondrial dysfunction, axonal transport defects, and gut microbiota dysbiosis, are involved in the pathogenesis of these six neurodegenerative diseases. Based on current information derived from diverse areas of research, these biological processes may form complex pathogenic networks that lead to distinctive types of neuronal death in neurodegenerative diseases. Furthermore, promoting the regeneration of damaged neurons may be achievable through the repair of affected neural cells if the underlying pathogenesis can be prevented or reversed. Hence, these potential common biological processes may represent only very small, limited elements within numerous intricate pathogenic networks associated with neurodegenerative diseases. In clinical treatment, interfering with any single biological process has proven insufficient to completely halt the progression of neurodegenerative diseases. Therefore, future research on the pathogenesis of neurodegenerative diseases should focus on uncovering the complex pathogenic networks, rather than isolating individual biological processes. Based on this, therapies that aim to block or reverse various targets involved in the potential pathogenic mechanisms of neurodegenerative diseases may be promising directions, as current treatment methods that focus on halting a single pathogenic factor have not achieved satisfactory efficacy.}, } @article {pmid40521002, year = {2025}, author = {Wei, Y and Rhee, H and Najafi, H and Blair, S and Kim, NC and Kim, WJ}, title = {Glial subtype-specific modulation of disease pathogenesis in Drosophila models of ALS.}, journal = {Genes & diseases}, volume = {12}, number = {5}, pages = {101631}, pmid = {40521002}, issn = {2352-3042}, } @article {pmid40520109, year = {2025}, author = {Evangelista, BA and Ragusa, JV and Pellegrino, K and Wu, Y and Quiroga-Barber, IY and Cahalan, SR and Arooji, OK and Madren, JA and Schroeter, S and Cozzarin, J and Xie, L and Chen, X and White, KK and Ezzell, JA and Iannone, MA and Cohen, S and Phanstiel, DH and Meeker, RB and Cohen, TJ}, title = {ALS-associated TDP-43 aggregates drive innate and adaptive immune cell activation.}, journal = {iScience}, volume = {28}, number = {6}, pages = {112648}, pmid = {40520109}, issn = {2589-0042}, support = {R01 AG066871/AG/NIA NIH HHS/United States ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is the most common and fatal motor neuron disease. Approximately 90% of ALS patients exhibit pathology of the master RNA regulator, transactive response DNA binding protein (TDP-43). Despite the prevalence TDP-43 pathology in ALS motor neurons, recent findings suggest immune dysfunction is a determinant of disease progression in patients. Whether TDP-43 aggregates elicit immune responses remains underexplored. In this study, we demonstrate that TDP-43 aggregates are internalized by antigen-presenting cell populations, cause vesicle rupture, and drive innate and adaptive immune cell activation by way of antigen presentation. Using a multiplex imaging platform, we observed enrichment of activated microglia/macrophages in ALS white matter that correlated with phosphorylated TDP-43 accumulation, CD8 T cell infiltration, and major histocompatibility complex expression. Taken together, this study sheds light on a novel cellular response to TDP-43 aggregates through an immunological lens.}, } @article {pmid40519505, year = {2025}, author = {Funo, K and Fukutake, T and Takeuchi, R and Uzawa, Y}, title = {Importance of Individualized Pressure Settings in Mechanical Insufflation-Exsufflation for Lung Volume Recruitment: A Case Report.}, journal = {Cureus}, volume = {17}, number = {5}, pages = {e84211}, pmid = {40519505}, issn = {2168-8184}, abstract = {Lung volume recruitment (LVR) has been proposed as a treatment to maintain respiratory health in patients with neuromuscular diseases who frequently develop restrictive ventilatory impairment due to muscle weakness. LVR applies noninvasive mechanical pressure techniques to maintain and improve pulmonary and chest wall compliance and to preserve vital capacity. Various methods of LVR have been developed, which can be classified into two types: the stacked-breath method and the single-breath method. Mechanical insufflation-exsufflation (MI-E) is one approach categorized under the single-breath method. Although the clinical use of pressure settings in MI-E varies, inspiratory pressure levels around 40 cmH2O are sometimes applied in practice. However, such settings may result in patient discomfort and raise safety concerns. Given the limited clinical guidance available, it may be more appropriate to determine individualized settings based on each patient's impairment level, pulmonary mechanics, and tolerance. This case report describes such an approach to LVR using the single-breath method with MI-E in a patient with amyotrophic lateral sclerosis (ALS). To determine the optimal inspiratory pressure, three parameters were assessed at each pressure level: expiratory volume, subjective perception of lung expansion, and immediate subjective effects following inspiration. As the patient reported discomfort at 30 cmH2O, the final inspiratory pressure was set at 25 cmH2O. This level of inspiratory assistance led to improvements in vocal loudness and alleviated breathlessness during speech. These positive effects contributed to the patient's acceptance of the intervention and its continued use after discharge to home care. This case highlights the importance of tailoring LVR settings to optimize effectiveness, patient comfort, and safety, based on pulmonary mechanics, bedside volume assessment, and patient-reported respiratory status.}, } @article {pmid40518845, year = {2025}, author = {Erdal, Y and Mahmutoglu, AS and Yavuz, N and Mahmutoglu, O and Emre, U}, title = {Assessment of cervical skeletal muscle index in early and late phases of amyotrophic lateral sclerosis.}, journal = {Neurological research}, volume = {}, number = {}, pages = {1-6}, doi = {10.1080/01616412.2025.2520010}, pmid = {40518845}, issn = {1743-1328}, abstract = {OBJECTIVES: The diagnosis of Amyotrophic Lateral Sclerosis (ALS) can be challenging when clinical and electrophysiological findings are insufficient. We aimed to investigate the potential role of cervical Skeletal Muscle Index (SMI), as a supportive diagnostic marker in ALS, particularly in relation to disease duration.

METHODS: A total of 22 ALS patients and 25 age- and sex-matched controls were retrospectively included. The cross-sectional area (CSA) of cervical muscles was measured on axial T1-weighted magnetic resonance imaging (MRI) at the C3 vertebra level. SMI was calculated by normalizing the total CSA to patient height (mm[2]/m[2]). ALS patients were stratified based on the timing of MRI: within six months of symptom onset and after six months.

RESULTS: There were no significant differences in age, sex, BMI, or total muscle volume between patients and controls. Although mean SMI was slightly lower in ALS patients (p = 0.177), this difference was not statistically significant. Among ALS patients, those who underwent MRI more than six months after symptom onset had significantly lower SMI values compared to both those who underwent MRI within six months and controls (respectively, p = 0.014, p = 0.018). No significant SMI difference was observed between ALS patients who underwent MRI within six months and controls (p = 0.626).

CONCLUSION: Cervical SMI measurements at the C3 vertebral level may support ALS diagnosis, particularly in patients with longer disease duration. SMI may also provide insight into early muscle loss due to denervation.}, } @article {pmid40518671, year = {2025}, author = {Val, GD and Gauye, F and Audrain, M and Menant, S and Ratnam, M and Chevalier, E and Ollier, R and Bhatia, D and Seredenina, T and Afroz, T and Pfeifer, A and Kosco-Vilbois, M and Nevoltris, D}, title = {A single dose of a vectorized mAb targeting TDP-43 potently inhibits the neuropathology in a model of ALS/FTD.}, journal = {Molecular therapy : the journal of the American Society of Gene Therapy}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ymthe.2025.06.026}, pmid = {40518671}, issn = {1525-0024}, abstract = {Transactive response DNA binding protein-43 (TDP-43)-mediated pathology is a hallmark of devastating neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Thus, monoclonal antibodies (mAbs) are being developed to target the pathological forms of this protein. To improve mAb exposure within the central nervous system, a potent anti-TDP-43 mAb, ACI-5891, was generated as a vectorized full-length antibody (vmAb) and evaluated for brain delivery using adeno-associated virus 9 (AAV9). Among the expression cassettes explored, the selected construct utilized an internal ribosome entry site (IRES), which produced high expression yields in vitro (>200 mg/L) with comparable quality, binding, and functional properties to the conventionally produced mAb. A single intracisternal administration of vmAb ACI-5891 demonstrated a broad brain distribution and sustained expression (i.e., months) in the serum, cerebrospinal fluid, and brain of mice. In a mouse model of ALS/FTD, treatment with a vmAb reduced the amount of pathological phospho-TDP-43 in neurons by 58% and 68% when expressed using either a ubiquitous promoter or a brain-selective promoter, respectively. This innovative approach sufficiently delivers effective immunotherapy with a single dose and illustrates the enormous potential of using vectorized antibodies to target neuropathology, including TDP-43 in patients suffering from ALS, FTD, and other TDP-43 proteinopathies.}, } @article {pmid40518263, year = {2025}, author = {Alali, S and Dubin, J and Hobin, F and Das, S and Lambrechts, C and Stoops, E and Vanmechelen, E and van Damme, P and Poesen, K}, title = {Serum neuronal pentraxin 2 levels are associated with shorter survival in amyotrophic lateral sclerosis.}, journal = {Journal of neurology, neurosurgery, and psychiatry}, volume = {}, number = {}, pages = {}, doi = {10.1136/jnnp-2025-336198}, pmid = {40518263}, issn = {1468-330X}, } @article {pmid40517187, year = {2025}, author = {Haro-Martínez, E and Muscolino, E and Moral, N and Duran, J and Fornaguera, C}, title = {Crossing the blood-brain barrier: nanoparticle-based strategies for neurodegenerative disease therapy.}, journal = {Drug delivery and translational research}, volume = {}, number = {}, pages = {}, pmid = {40517187}, issn = {2190-3948}, support = {2021 SGR 00537//Agència de Gestió d'Ajuts Universitaris i de Recerca/ ; 2024-LLAV-00042//Agència de Gestió d'Ajuts Universitaris i de Recerca/ ; ICREA Acadèmia 2024//Agència de Gestió d'Ajuts Universitaris i de Recerca/ ; 202207-31//Fundació la Marató de TV3/ ; PID2020-118699GB-100//Agencia Estatal de Investigación/ ; Not specified//Fundación Ramón Areces/ ; FISDUR-2024//Departament d'Universitats, Recerca i Societat de la Informació/ ; }, abstract = {Neurodegenerative conditions, including Alzheimer's, Parkinson's, amyotrophic lateral sclerosis, and Huntington's disease, represent a critical medical challenge due to their increasing prevalence, severe consequences, and absence of curative treatments. Beyond the need for a deeper understanding of the fundamental mechanisms underlying neurodegeneration, the development of effective treatments is hindered by the blood-brain barrier, which poses a major obstacle to delivering therapeutic agents to the central nervous system. This review provides a comprehensive analysis of the current landscape of nanoparticle-based strategies to overcome the blood-brain barrier and enhance drug delivery for the treatment of neurodegenerative diseases. The nanocarriers reviewed in this work encompass a diverse array of nanoparticles, including polymeric nanoparticles (e.g. micelles and dendrimers), inorganic nanoparticles (e.g. superparamagentic iron oxide nanoparticles, mesoporous silica nanoparticles, gold nanoparticles, selenium and cerium oxide nanoparticles), lipid nanoparticles (e.g. liposomes, solid lipid nanoparticles, nanoemulsions), as well as quantum dots, protein nanoparticles, and hybrid nanocarriers. By examining recent advancements and highlighting future research directions, we aim to shed light on the promising role of nanomedicine in addressing the unmet therapeutic needs of these diseases.}, } @article {pmid40516772, year = {2025}, author = {Rawat, E and Sharma, S and Vyas, S and Alsaidan, OA and Kapoor, DU and Prajapati, BG}, title = {Advances in alginate-based nanoformulations: Innovative and effective strategies for targeting and treating brain disorders.}, journal = {International journal of pharmaceutics}, volume = {681}, number = {}, pages = {125851}, doi = {10.1016/j.ijpharm.2025.125851}, pmid = {40516772}, issn = {1873-3476}, mesh = {*Alginates/chemistry/administration & dosage ; Humans ; *Brain Diseases/drug therapy ; Animals ; *Drug Delivery Systems/methods ; *Nanoparticles/chemistry/administration & dosage ; Blood-Brain Barrier/metabolism ; Drug Carriers/chemistry ; }, abstract = {Brain disorders, encompassing neurodegenerative conditions and intracranial neoplasms, present formidable obstacles in the realm of pharmacological delivery due to the existence of athe blood-brain barrier (BBB) and the restricted bioavailability of therapeutic agents. Alginate-derived nanoformulations have emerged as highly promising systems for drug delivery, offering attributes such as biocompatibility, regulated release, and improved targeting efficacies. This review investigates contemporary advancements in alginate-based nanoformulations, with a particular emphasis on their efficacy in surmounting obstacles to successful pharmacological delivery to the brain. Initially, we furnish a comprehensive overview of alginate, underscoring its pertinent properties, biomedical applications, and inherent limitations. Subsequently, the discourse progresses to strategies for nanoformulation, which encompass lipid-based, polymeric, and inorganic methodologies, with a focus on their benefits in relation to cerebral targeting. Moreover, this review entails the therapeutic potential of alginate-based nanoformulations in addressing significant neurological disorders, including Alzheimer's disease, Parkinson's disease, brain tumours, traumatic brain injury, epilepsy, and amyotrophic lateral sclerosis. By amalgamating cutting-edge nanotechnology with the distinctive properties of alginate, these formulations signify a promising pathway for the advancement of efficacious therapies aimed at brain targeting. Additionally, prospective research trajectories and challenges associated with the optimization of alginate-based nanocarriers for clinical applications are also elucidated.}, } @article {pmid40516596, year = {2025}, author = {Kitamura, K and Tsukui, I and Sasaki, F and Shiramasa, Y and Arayama, M and Morishita, M and Oshima, A and Kitazawa, S and Kameda, T and Kitahara, R}, title = {ATP as a Key Modulator of Fused-in-sarcoma Phase Separation and Aggregation: Insights into Amyotrophic Lateral Sclerosis Pathogenesis.}, journal = {Journal of molecular biology}, volume = {437}, number = {17}, pages = {169295}, doi = {10.1016/j.jmb.2025.169295}, pmid = {40516596}, issn = {1089-8638}, mesh = {*RNA-Binding Protein FUS/metabolism/chemistry/genetics ; *Amyotrophic Lateral Sclerosis/metabolism/pathology/genetics ; *Adenosine Triphosphate/metabolism/chemistry ; Humans ; Molecular Dynamics Simulation ; Protein Aggregates ; *Protein Aggregation, Pathological/metabolism ; Phase Separation ; }, abstract = {Fused in sarcoma (FUS) is an RNA-binding protein, the aberrant aggregation of which is linked to amyotrophic lateral sclerosis (ALS). Liquid-liquid phase separation (LLPS) of FUS facilitates functional condensate formation and can drive pathological aggregation under certain conditions. The aggregation-inhibitory effects of ATP, a key cellular hydrotrope, have been reported for multiple proteins; however, how ATP, present at approximately 1-12 mM concentrations in cells, regulates LLPS and amyloid fibril formation remains unclear. Therefore, we investigated how ATP modulates the LLPS behavior and aggregation of FUS and its ALS-linked variants, R495X and P525L. ATP destabilized both normal LLPS and aberrant high-pressure LLPS (HP-LLPS), with a relatively strong inhibitory effect on HP-LLPS. Pressure-jump experiments demonstrated that ATP reduced the irreversible aggregation propensity of HP-LLPS, particularly in ALS variants that exhibited enhanced aggregation compared to that by wild-type FUS. Molecular dynamic simulations further revealed that the triphosphate and adenosine moieties of ATP synergistically disrupted intermolecular interactions that were crucial for phase separation, leveraging its amphipathic properties. Notably, ATP concentrations within the physiological range (1-12 mM) significantly inhibited FUS aggregation, suggesting a protective role in cellular environments. These results indicate that decreased intracellular ATP levels may exacerbate aberrant phase transitions of FUS, contributing to ALS onset. This study underscores the potential of ATP as a therapeutic modulator of protein phase separation and aggregation, providing valuable insights into the molecular mechanisms of ALS. Our findings open new avenues for targeting ATP-regulated pathways for treating neurodegenerative disorders.}, } @article {pmid40516449, year = {2025}, author = {Yadav, AJ and Padhi, AK}, title = {Synergizing multiresolution simulations, interface redesign, and hotspot mapping to decipher pathogenic mutation-driven structural modulation in VCP.}, journal = {Computers in biology and medicine}, volume = {194}, number = {}, pages = {110560}, doi = {10.1016/j.compbiomed.2025.110560}, pmid = {40516449}, issn = {1879-0534}, mesh = {*Valosin Containing Protein/genetics/chemistry/metabolism ; Humans ; *Molecular Dynamics Simulation ; *Mutation, Missense ; Mutation ; }, abstract = {Valosin-containing protein (VCP/p97), a pivotal AAA[+] ATPase, orchestrates proteostasis via ER-associated degradation (ERAD), ubiquitin-mediated proteolysis, and organelle surveillance. Pathogenic missense mutations, notably Arg95Gly (R95G) within the evolutionarily conserved double-ψ β-barrel (DPBB) of its N-terminal domain, are implicated in proteinopathies including IBMPFD and ALS. To decode the structural-dynamics perturbations underpinning R95G-driven dysfunction, we integrated AlphaFold3-based modeling, protein-peptide docking, and multiscale enhanced-sampling molecular dynamics (MD) simulations-spanning 1.2 μs all-atom, 12 μs coarse-grained, and umbrella sampling regimes. Our findings reveal that R95G disrupts the β-barrel integrity, destabilizes long-range domain coupling, and engenders conformational heterogeneity deleterious to gp78 cofactor recruitment. Free-energy landscapes of the mutant highlight enthalpically disfavored, low-occupancy binding conformers, corroborated by MM/PBSA-based end-state binding free energy and potential of mean force (PMF) analyses, which indicate impaired binding thermodynamics. Interface hotspot mapping pinpoints dynamic perturbations at critical residues that propagate allosteric decoupling and morphological distortion of the binding interface. Collectively, our results delineate a mechanistic cascade-from local β-barrel destabilization to global interaction network disruption-underlying VCP's functional impairment in disease states. This work provides a computationally derived structural framework to inform targeted biophysical validation and the rational design of therapeutic strategies aimed at rescuing VCP function in IBMPFD and ALS.}, } @article {pmid40515975, year = {2025}, author = {Zhu, Y and Neyrinck, K and Burg, T and Chai, YC and Nami, F and Ahuja, K and Swinnen, JV and Van Den Bosch, L and Verfaillie, C}, title = {Altered Lipid Homeostasis in Mutant FUS[R521H] Astrocytes from HiPSCs.}, journal = {Molecular neurobiology}, volume = {}, number = {}, pages = {}, pmid = {40515975}, issn = {1559-1182}, support = {201908440360//China Scholarship Council/ ; 12AIK24N//Fonds Wetenschappelijk Onderzoek/ ; FWO-SBO-S001221N -ORGAN-ID//Fonds Wetenschappelijk Onderzoek/ ; C14-17-107//University of Leuven C1 grants/ ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by motor neuron loss, leading to paralysis and death. Mutations in the fused in sarcoma (FUS) gene cause early-onset ALS with rapid disease progression. Although motor neuron degeneration is central to ALS, recent studies highlight a significant role for dysfunctional glial cells, particularly astrocytes, in disease progression. In this study, we generated astrocytes from FUS[R521H] mutant and isogenic human induced pluripotent stem cells (hiPSCs) by inducible overexpressing SOX9. Lipidomic analysis revealed marked glycerophospholipid deficiencies in FUS[R521H] mutant astrocytes, especially reduced phosphatidylcholine (PC) and phosphatidylinositol (PI) levels. This reduction in PC was also observed in FUS[R521H] mutant oligodendroglial progenitors and motor neurons, suggesting a potential dysregulation of glycerophospholipid metabolism across multiple central nervous system (CNS) cell types in FUS-ALS. These observations highlight the need for further investigation into lipid dysregulation and its relevance to FUS-ALS pathogenesis.}, } @article {pmid40515812, year = {2025}, author = {Jellinger, KA}, title = {Prevalence and impact of comorbidities in amyotrophic lateral sclerosis.}, journal = {Journal of neural transmission (Vienna, Austria : 1996)}, volume = {}, number = {}, pages = {}, pmid = {40515812}, issn = {1435-1463}, support = {Society for the Promotion of Research in Experimental Neurology, Vienna, Austria//Society for the Promotion of Research in Experimental Neurology, Vienna, Austria/ ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease of multifaceted nature and variable progression that poses considerable challenges to our understanding of its evolution and interplay with different comorbid conditions. The etiopathogenesis of ALS is still unexplained and multimorbidity is common, but its influence on the ALS susceptibility and disease course is a matter of discussion. This study using medical databases tries to find diseases associated with ALS and their impact on disease onset and progression. Diseases associated with the risk of ALS include diabetes mellitus, dyslipidemias and cardiovascular comorbidities that may play an important role in the prognosis of ALS. Hypometabolic disorders and cardiovascular diseases may have a protective effect on ALS incidence, while coronary heart disease and hypertension have a negative effect on disease progression. Other comorbidities include Parkinson disease, TDP-43 pathology, progressive supranuclear palsy, progressive aphasia, myasthenia gravis, cancer and autoimmune disorders, while there is no evidence for a shared genetic background of common risk variants in ALS and multiple sclerosis. Among non-motor manifestations of ALS, cognitive and behavioral impairments are important. Other comorbidities include sleep disorders, traumatic encephalopathy, sarcoidosis, prionopathies, schizophrenia, cervical spondylotic myelopathy, psoriasis and others. The tremendous heterogeneity of concomitant pathologies and comorbidities observed across the ALS spectrum may be caused by a complex interplay between genetic, pathogenetic, inflammatory and other risk factors that are still poorly understood. Further research should provide increasing insight into their relationship with motor system disorders in order to find better diagnostic tools and probable effective therapies for these disease-modifying comorbidities.}, } @article {pmid40514455, year = {2025}, author = {Hu, YQ and Zhang, XX and Zhao, TT and Wu, XH}, title = {Using proteomics and single-cell sequencing to analyze the pathogenesis of recurrent implantation failure associated with uterine natural killer cells.}, journal = {Archives of gynecology and obstetrics}, volume = {}, number = {}, pages = {}, pmid = {40514455}, issn = {1432-0711}, support = {H2023106006//Natural Science Foundation of Hebei Province/ ; 213777102D//The Key Research and Development project of Hebei Province/ ; 20251109//Medical Science Research Project of Hebei/ ; }, abstract = {PROBLEM: Recurrent implantation failure (RIF) affects about 10% of infertility patients and may involve mid-luteal phase endometrial natural killer (NK) cells. The pathogenesis of NK cells in RIF remains unclear.

METHOD OF STUDY: Our study integrated proteomics data from endometrial tissues of six RIF patients and six controls, with single-cell sequencing insights.

RESULTS: Our proteomics analysis identified 1366 differentially expressed proteins (DEPs) between RIF and control groups, highlighting alterations in cellular processes, such as cytoplasmic translation and mRNA processing. Functional enrichment analysis revealed significant associations with pathways involved in amyotrophic lateral sclerosis and proteasomes. The DEPs were transformed into differentially expressed genes1 (DEGs1) by ID-transformation. 33 candidate genes were detected when ID-transformed 1210 DEGs1 were intersected with 752 DEGs2 from NK cells. After that, the proteomics sequencing data validation showed that the expression of AMPD3, H6PD, and PAK2 was consistent and significantly different from the GSE111974 dataset and classified as crucial genes. In addition, analysis of single-cell sequencing data annotated fibroblast-like stromal cells, NK cells, T cells, and endothelial cells, and these three essential genes showed that they were expressed in NK cells. Crossing the signaling pathways of key genes with those enriched for DEPs yielded the 'Escherichia coli infection' possibly associated with RIF. Finally, the transcription factor HR had a strong regulatory effect on the PAK2.

CONCLUSION: Finally, identifying three key genes (AMPD3, H6PD and PAK2) associated with RIF and the regulatory solid roles of HR and PAK2 provided a basis for understanding the molecular mechanism of RIF. Our findings may pave the way for developing targeted therapies to improve pregnancy outcomes in patients with RIF.}, } @article {pmid40514097, year = {2025}, author = {Artuğ, NT and Sirin, NG and Baslo, SA and Orhan, EK and Baslo, MB and Oge, AE}, title = {Automated step analysis algorithm for CMAP scan study.}, journal = {Medical engineering & physics}, volume = {141}, number = {}, pages = {104353}, doi = {10.1016/j.medengphy.2025.104353}, pmid = {40514097}, issn = {1873-4030}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology/diagnosis ; Male ; Middle Aged ; Female ; *Algorithms ; Automation ; *Action Potentials ; Aged ; Adult ; Software ; Reproducibility of Results ; Case-Control Studies ; *Electromyography/methods ; }, abstract = {OBJECTIVE: To create an automated method for step analysis in compound muscle action potential (CMAP) scan curves and compare the step parameters calculated using the conventional semi-automated and the new automated method between patients with amyotrophic lateral sclerosis (ALS) and controls.

METHODS: Twenty ALS patients and fifteen controls were enrolled into the study. Median nerve was stimulated at the wrist to record CMAP scans from abductor pollisis brevis muscle. Automated step analysis software revealed gaps on CMAP scan graphics by using new parameters indicating the steps. New parameters were calculated and compared with the conventional semi-automated step analysis. Intra-class correlation coefficients (ICC) were measured for reliability between methods.

RESULTS: Step parameters calculated by two methods showed no significant difference in patients with ALS, except step%, but their similarities were less favorable in controls. The reliability of parameters between two methods was good-to-excellent in patient group, but controls did not show a significant ICC for any of the parameters.

CONCLUSION: A completely new automated step analysis software was developed. Analyses were done within 5 s. New step parameters were presented with supporting graphics. Results of automated step analysis were in concordance with semi-automated one for ALS patients, but not in controls.}, } @article {pmid40513650, year = {2025}, author = {Ho, CY and Chang, YJ and Yang, CW and Shih, O and Jeng, US and Hwang, IS and Huang, WC and Chen, YR}, title = {Membrane Disruption Properties of Poly-Glycine Arginine Dipeptide Repeats Affected by Peptide Repeats Continuity and Membrane Composition.}, journal = {Journal of molecular biology}, volume = {437}, number = {17}, pages = {169296}, doi = {10.1016/j.jmb.2025.169296}, pmid = {40513650}, issn = {1089-8638}, mesh = {*Cell Membrane/metabolism/chemistry ; Humans ; C9orf72 Protein/genetics ; *Peptides/chemistry/metabolism ; *Dipeptides/chemistry/metabolism ; Liposomes/chemistry/metabolism ; Animals ; Mice ; }, abstract = {C9ORF72 hexanucleotide expansion is the most common genetic mutation in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTD). This expansion can be translated into dipeptide repeats (DPRs) through repeat-associated non-ATG (RAN) translation. Arginine-rich DPRs, i.e., poly-glycine arginine (poly-GR) and poly-proline arginine (poly-PR) are considered the most toxic ones among the five types of DPRs. We recently discovered that poly-GR forms helical conformation and is able to penetrate cell membranes, leading to cytotoxicity, but the mechanism remains unclear. Here, we investigated the membrane disruption mechanism of poly-GR related to its sequence and membrane composition. To test this, we stopped its continuously repeated sequence by inserting several proline residues to disrupt its helical structure. We found that the modification reduced its cytotoxicity and membrane disruption capability. Next, we examined the influence of lipid composition on the membrane-disrupting ability of poly-GR using various liposomes. Poly-GR caused higher leakage in the negatively charged liposomes compared to the neutral or positively charged ones. Cholesterol content affected the extent of disruption, while gangliosides had no significant effect. Using small-angle x-ray scattering (SAXS), total internal reflection fluorescence (TIRF) microscopy, and atomic force microscopy (AFM), we observed the behavior of poly-GR on lipid membranes. Finally, we directly treated mouse neuroblastoma to modulate the cholesterol content and found that cholesterol depletion inhibited the internalization of poly-GR into the cells and reduced cytotoxicity. These findings reveal that the conformation of poly-GR and the lipid composition influence its membrane penetration, offering insights into potential therapeutic strategies for C9ORF72-related diseases.}, } @article {pmid40513028, year = {2025}, author = {Bromberg, MB}, title = {What Is in the Literature.}, journal = {Journal of clinical neuromuscular disease}, volume = {26}, number = {4}, pages = {176-183}, doi = {10.1097/CND.0000000000000526}, pmid = {40513028}, issn = {1537-1611}, mesh = {Humans ; *Motor Neuron Disease/therapy/diagnosis ; *Amyotrophic Lateral Sclerosis/therapy/diagnosis ; }, abstract = {This issue of What Is in the Literature focuses on articles over the past year on clinical aspects of motor neuron disease, including amyotrophic lateral sclerosis (ALS) and primary lateral sclerosis (PLS). Disease-modifying treatment for ALS remains a challenge as 2 formal drug trials did not hold up to retesting. There are new thoughts based on a multistep model to partially explain why ALS develops relatively late in life. New information on fluid biomarkers, sex differences, efficacy of medical marijuana for common symptoms, and cognitive dysfunction are discussed. For the clinic, there are updated guidelines for multidisciplinary management. Other articles address how frequently the topic of sexual health is brought up in the clinic, and insights into how patients view end-of-life issues and quality of life when using tracheal ventilation. PLS has diagnostic challenges and practical aspects, which are reviewed.}, } @article {pmid40511876, year = {2025}, author = {Yeole, A and Khanna, L and Doshi, M and Sharma, A and Uttarwar, P and Doshi, S and Kaushik Kumar, R and Venkataramana, N and Parmar, D}, title = {A phase 2, proof-of-concept, placebo-controlled, randomized, multicenter, double-blind study to evaluate the efficacy, safety, tolerability, pharmacokinetics, and pharmacodynamics of Usnoflast (ZYIL1) in patients with amyotrophic lateral sclerosis.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {}, number = {}, pages = {1-8}, doi = {10.1080/21678421.2025.2515900}, pmid = {40511876}, issn = {2167-9223}, abstract = {Objective: To assess the efficacy, safety, pharmacokinetics (PK), and pharmacodynamics (PD) of Usnoflast (ZYIL1) in patients with amyotrophic lateral sclerosis (ALS). Methods: Patients with a probable or definite ALS diagnosis were randomized to receive twice daily oral doses (for 12 weeks) of Usnoflast (25 mg, 50 mg, or 75 mg) or placebo. The primary outcome was the change in ALS functional rating scale-revised (ALSFRS-R) total score from baseline to week 12. Secondary outcomes were assessment of PK, change in slow vital capacity (SVC) and serum and cerebrospinal fluid (CSF) levels of neurofilament light (NfL) chain from baseline to week 12, and safety up to 12 weeks. Results: Total 24 patients were enrolled; 71% of those who received Usnoflast had the drug above therapeutic concentration in CSF. In the modified intent-to-treat (mITT) population, least square mean changes (ANCOVA) in ALSFRS-R total score from baseline to week 12 were -1.91 for Usnoflast 25 mg, -3.84 for Usnoflast 50 mg, 0.52 for Usnoflast 75 mg, and -2.26 for placebo arm. Though not significant (p > 0.05), compared with placebo, Usnoflast 75 mg demonstrated a difference of 2.78 (mITT) and 3.28 (per-protocol) in ALSFRS-R total score. Statistical non-significant differences were also observed in changes of SVC% and CSF NfL levels. Usnoflast was well-tolerated at tested doses, and there was no treatment-emergent serious adverse event or death during the study duration. Conclusion: Usnoflast 50 and 75 mg doses were well-tolerated in ALS patients, providing rationale for further studies of Usnoflast in ALS.}, } @article {pmid40511793, year = {2025}, author = {Parks, ASE and Gotlib Conn, L and Amog, K and Bodmer, NS and King, JW and McLaren, AMR and Reid, M and Kishibe, T and Abrahao, A and Zinman, L and Sale, JEM}, title = {Age and life stage in the experience of amyotrophic lateral sclerosis: a scoping review.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {}, number = {}, pages = {1-27}, doi = {10.1080/21678421.2025.2515914}, pmid = {40511793}, issn = {2167-9223}, abstract = {Objective: Understanding the experiences of people living with amyotrophic lateral sclerosis (plwALS) is necessary to appreciate their unique needs. Age and stage in the life course influence how illness is experienced; however, the extent to which age-specific complexities of living with ALS have been examined remains unexplored. This review aims to map the available evidence exploring age, age-graded role, or life-course transition with regards to the experience of ALS and to identify age-specific gaps in the literature. Methods: A scoping review guided by Joanna Briggs Institute methodology was undertaken. Eligible articles included peer-reviewed primary research studies, published in English from 2010 onward, investigating illness experience of adults with ALS with consideration for how age, age-graded roles, or life-course transitions influenced experience. Database sources included: Ovid's Medline, Embase, and PsycINFO; EBSCO CINAHL; and ProQuest Sociological Abstracts. Findings related to ALS experience and dimensions of age were summarized descriptively and categorized using qualitative content analysis. Results: Six thousand one hundred and eighty individual records were identified and screened. Forty-five articles, reporting 42 studies, were included. Findings regarding thoughts, feelings, or emotions of plwALS were most common and varied depending on whether they were in reference to chronological age or age-graded role. Despite the importance of life-course transitions for illness experience, they were not routinely considered. Conclusion: Numerous aspects of the experience of plwALS have been reported in reference to age; however, the significance of age-graded roles and life-course transitions warrants further examination. Recognition of age-related complexities of living with ALS will facilitate more personalized ALS care.}, } @article {pmid40510242, year = {2025}, author = {Pfaff, AL and Bubb, VJ and Quinn, JP and Kõks, S}, title = {The landscape of non-reference SINE-VNTR-Alus in amyotrophic lateral sclerosis.}, journal = {Experimental biology and medicine (Maywood, N.J.)}, volume = {250}, number = {}, pages = {10600}, pmid = {40510242}, issn = {1535-3699}, mesh = {*Amyotrophic Lateral Sclerosis/genetics ; Humans ; *Minisatellite Repeats/genetics ; Genetic Predisposition to Disease ; Male ; Female ; *Short Interspersed Nucleotide Elements/genetics ; Middle Aged ; Gene Frequency ; }, abstract = {The fatal neurodegenerative disease, amyotrophic lateral sclerosis (ALS), leads to the degeneration of motor neurons in the brain and spinal cord. Many different genetic variants are known to increase the risk of developing ALS, however much of the disease heritability is still to be identified. To identify novel genetic factors, we characterised SINE-VNTR-Alu (SVA) presence/absence variation in 4403 genomes from the New York Genome Center (NYGC) ALS consortium. SVAs are a type of retrotransposon able to mobilise in the human genome generating new insertions that can modulate gene expression and mRNA splicing and to date 33 insertions are known to cause a range of genetic diseases. In the NYGC ALS consortium sequence data 2831 non-reference genome SVAs were identified and 95% of these insertions were rare with an insertion allele frequency of less than 0.01. Association analysis of the common SVAs with ALS risk, age at onset and survival did not identify any SVAs that survived correction for multiple testing. However, there were three different rare SVA insertions in the ALS associated gene NEK1 identified in four different individuals with ALS. The frequency of these rare insertions in NEK1 was significantly higher in the individuals with ALS from the NYGC ALS consortium compared to the gnomAD SV non-neuro controls (p = 0.0002). This study was the first to characterise non-reference SVA presence/absence variation in a large cohort of ALS individuals identifying insertions as potential candidates involved in disease development for further investigation.}, } @article {pmid40510202, year = {2025}, author = {Li, L and Lv, L and Wang, Z and Liu, X and Wang, Q and Zhu, H and Jiang, B and Han, Y and Pan, X and Zhou, X and Ren, L and Chang, Z}, title = {From copper homeostasis to cuproptosis: a new perspective on CNS immune regulation and neurodegenerative diseases.}, journal = {Frontiers in neurology}, volume = {16}, number = {}, pages = {1581045}, pmid = {40510202}, issn = {1664-2295}, abstract = {Copper, an essential trace element for the human body, plays a key role in energy metabolism, mitochondrial respiration, redox reactions, and neural signal transmission. The recently proposed concept of "cuproptosis" has further revealed the unique status of copper in cellular regulation: when copper abnormally accumulates within cells, it can directly bind to the lipoylated proteins of the mitochondrial TCA cycle, triggering protein aggregation and metabolic disorders, ultimately leading to cell death. This form of cell death plays an important role in various neurodegenerative diseases of the central nervous system, such as Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), and stroke. This review summarizes recent research on the mechanisms of cuproptosis, providing new perspectives and a theoretical basis for understanding the pathogenesis of these neurodegenerative diseases.}, } @article {pmid40509360, year = {2025}, author = {Chang, B and Huang, J and Xie, Q and Ruan, Y and Liu, R}, title = {Identification, Geographical Traceability, and Thermal Oxidation and Photodegradation Studies of Camellia Oil Based on Raman Spectroscopy.}, journal = {Molecules (Basel, Switzerland)}, volume = {30}, number = {11}, pages = {}, pmid = {40509360}, issn = {1420-3049}, support = {2024KY0802, 2023KY0217,XJ21KT29//the Middle-aged and Young Teachers' Basic Ability Promotion Project of Guangxi，The Guilin University of Aerospace Technology School Fund/ ; No. AD25069073//Guangxi Science and Technology Program Project/ ; }, mesh = {*Spectrum Analysis, Raman/methods ; *Plant Oils/chemistry/analysis ; *Camellia/chemistry ; Oxidation-Reduction ; Photolysis ; Carotenoids/chemistry/analysis ; Temperature ; Least-Squares Analysis ; Discriminant Analysis ; }, abstract = {Camellia oil, rich in monounsaturated fatty acids, squalene, tocopherols, and polyphenols, is highly valued for its nutritional benefits. However, its high market value and regional variations have led to frequent adulteration, highlighting the need for rapid, non-destructive methods for authentication, geographical traceability, and quality assessment. This study employed portable Raman spectroscopy combined with Partial Least Squares Discriminant Analysis (PLS-DA) and Multivariate Curve Resolution-Alternating Least Squares (MCR-ALS) to differentiate camellia oil from other edible oils and evaluate its thermal and photo-oxidative stability. PLS-DA, based on VIP-selected spectral variables, effectively distinguished camellia oil, with Raman bands near 1250 cm[-1] and 1650 cm[-1] contributing significantly. A unique peak at 1525 cm[-1], observed in samples from Gongcheng, Guangxi, was associated with carotenoids and served as a potential marker for geographical traceability. MCR-ALS modeling revealed significant reductions in the 1650 cm[-1] and 1525 cm[-1] peaks when temperatures exceeded 150 °C, indicating degradation of unsaturated fatty acids and carotenoids. Under UV exposure, the 1525 cm[-1] peak declined sharply and nearly disappeared after 24 h, suggesting rapid carotenoid degradation via photooxidation. Extended UV treatment also affected the 1650 cm[-1] peak and led to oxidative product accumulation. Overall, this study demonstrates the feasibility of integrating Raman spectroscopy with chemometric analysis for efficient oil classification, traceability, and stability monitoring, offering a valuable tool for food quality control and market supervision.}, } @article {pmid40508048, year = {2025}, author = {Tolochko, C and Shiryaeva, O and Alekseeva, T and Dyachuk, V}, title = {Amyotrophic Lateral Sclerosis: Pathophysiological Mechanisms and Treatment Strategies (Part 2).}, journal = {International journal of molecular sciences}, volume = {26}, number = {11}, pages = {}, pmid = {40508048}, issn = {1422-0067}, mesh = {*Amyotrophic Lateral Sclerosis/physiopathology/drug therapy/metabolism/therapy/etiology/pathology ; Humans ; Oxidative Stress/drug effects ; Animals ; Antioxidants/therapeutic use/pharmacology ; Motor Neurons/metabolism/pathology/drug effects ; Glutamic Acid/metabolism ; Neuroprotective Agents/therapeutic use ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease associated with damage to motor neurons and leading to severe muscle weakness and, eventually, death. Over the past decade, understanding of the key pathogenetic links of ALS, including glutamate-mediated excitotoxicity and oxidative stress, has significantly advanced. This review considers the recent evidence on molecular mechanisms of these processes, as well as the therapeutic strategies aimed at their modulation. Special attention is paid to antiglutamatergic and antioxidant drugs as approaches to the ALS pathogenetic therapy.}, } @article {pmid40507679, year = {2025}, author = {Zhou, Y and Ni, Y and Lan, L and Wan, H and Luo, F}, title = {Association Between Allostatic Load and Delirium in ICU Patients: A Retrospective Analysis of the MIMIC-IV Database.}, journal = {Journal of clinical medicine}, volume = {14}, number = {11}, pages = {}, pmid = {40507679}, issn = {2077-0383}, support = {82300118//National Natural Science Foundation of China/ ; }, abstract = {Background: Allostatic load reflects the cumulative physiological effects of chronic and repeated stress on the body and is associated with dysregulation of multiple systems. This study aimed to examine the association between the allostatic load score (ALS) and the development of delirium in intensive care unit (ICU) patients. Method: The adult patients from the Medical Information Mart for Intensive Care (MIMIC-IV) database were screened and included in this study. Allostatic load was scored by hemoglobin A1c, high-density lipoprotein, total cholesterol, systolic blood pressure, diastolic blood pressure, body mass index, C-reactive protein, and serum albumin, and varied from 0 to 8. Restricted cubic spline and multivariate logistic regression were used to assess the relationship between ALS and delirium risk in the ICU. The threshold of the ALS was determined by the decision tree approach. A sensitivity analysis was also conducted. Results: A total of 656 patients were included in the study, and the incidence of delirium was 50.6% (n = 332). In a fully adjusted restricted cubic spline model, an increase in ALS was linearly positively correlated with the occurrence of delirium in the ICU (p-overall = 0.039, p-nonlinear = 0.506). The threshold for ALS was determined to be 3. ALS ≥ 3 was associated with increased delirium rates (p < 0.001), longer hospital stays (p < 0.001), and higher in-hospital mortality (p = 0.002). Subgroup analyses revealed no significant interactions (all p values for interactions > 0.05). Conclusions: Higher ALS was linearly associated with increased risk of ICU delirium. An ALS ≥ 3 identified patients with greater delirium incidence, longer hospital stays, and higher mortality.}, } @article {pmid40506843, year = {2025}, author = {Ashford, BA and Simpson, JE and Dawson, C and Boche, D and Cooper-Knock, J and Heath, PR and Fillingham, D and Appleby-Mallinder, C and Wei, W and Dunning, M and Highley, JR}, title = {Human amyotrophic lateral sclerosis/motor neuron disease: The disease-associated microglial pathway is upregulated while APOE genotype governs risk and survival.}, journal = {Brain pathology (Zurich, Switzerland)}, volume = {}, number = {}, pages = {e70019}, doi = {10.1111/bpa.70019}, pmid = {40506843}, issn = {1750-3639}, support = {//Bruker Spatial Biology/ ; //British Neuropathological Society/ ; //Pathological Society of Great Britain and Ireland/ ; }, abstract = {A key role for inflammation in amyotrophic lateral sclerosis/motor neuron disease (ALS/MND) has been identified. It is vital to assess which central nervous system structures are most affected and which inflammatory processes are responsible in humans. The inflammatory transcriptome was characterized in the cervical spinal cord and motor cortex in post-mortem frozen and formalin-fixed paraffin-embedded specimens from human sporadic ALS/MND and control cases using the nCounter® Neuroinflammation Panel. Archival data were reanalyzed and compared with the nCounter data. Immunohistochemistry was used to examine the inflammatory response in the spinal cord and motor cortex and validate changes found during transcriptomic analyses. In the spinal cord, marked inflammation was observed, while less inflammation was detected in the motor cortex. Examination of differentially expressed genes in the spinal cord highlighted TREM2, TYROBP, APOE, and CD163, as well as phagocytic pathways. In sporadic ALS/MND spinal cord, significant microglial reactivity and involvement of TREM2, ApoE (encoded by APOE), and TYROBP were confirmed, suggesting the involvement of the disease-associated microglial (DAM) phenotype. The corticospinal tracts showed greater inflammation than the ventral horns. The precentral gyrus of ALS/MND again showed less immune reactivity to disease when compared to controls. Finally, in the largest cohort assessed to date, we demonstrate an association between the APOE variant and ALS/MND risk, age of onset, and survival. We find confirmed associations between APOE ε3/ε3 and disease and between ε2/ε2 and absence of disease. Further, ε4/ε4 appears to be associated with earlier disease onset and a more aggressive course. We conclude that while there is widespread inflammation in the CNS in sporadic ALS/MND, this is more marked in the spinal cord, especially the corticospinal tract. The specific markers stress the DAM phenotype as having a key role together with a possible influx of somatic macrophages. In addition, APOE function and genotype may be relevant in ALS/MND.}, } @article {pmid40506548, year = {2025}, author = {Wairagkar, M and Card, NS and Singer-Clark, T and Hou, X and Iacobacci, C and Miller, LM and Hochberg, LR and Brandman, DM and Stavisky, SD}, title = {An instantaneous voice-synthesis neuroprosthesis.}, journal = {Nature}, volume = {644}, number = {8075}, pages = {145-152}, pmid = {40506548}, issn = {1476-4687}, support = {DP2 DC021055/DC/NIDCD NIH HHS/United States ; }, mesh = {*Brain-Computer Interfaces ; Humans ; Male ; *Voice/physiology ; *Speech/physiology ; Amyotrophic Lateral Sclerosis/physiopathology/rehabilitation/complications ; Dysarthria/rehabilitation/physiopathology ; *Neural Prostheses ; Electrodes, Implanted ; Microelectrodes ; Communication Devices for People with Disabilities ; }, abstract = {Brain-computer interfaces (BCIs) have the potential to restore communication for people who have lost the ability to speak owing to a neurological disease or injury. BCIs have been used to translate the neural correlates of attempted speech into text[1-3]. However, text communication fails to capture the nuances of human speech, such as prosody and immediately hearing one's own voice. Here we demonstrate a brain-to-voice neuroprosthesis that instantaneously synthesizes voice with closed-loop audio feedback by decoding neural activity from 256 microelectrodes implanted into the ventral precentral gyrus of a man with amyotrophic lateral sclerosis and severe dysarthria. We overcame the challenge of lacking ground-truth speech for training the neural decoder and were able to accurately synthesize his voice. Along with phonemic content, we were also able to decode paralinguistic features from intracortical activity, enabling the participant to modulate his BCI-synthesized voice in real time to change intonation and sing short melodies. These results demonstrate the feasibility of enabling people with paralysis to speak intelligibly and expressively through a BCI.}, } @article {pmid40505784, year = {2025}, author = {Tang, J and Kang, Y and Chen, Q and Zhang, B and Shang, N and Lan, J and Wu, L and Peng, Y}, title = {TIMP1 inhibits Rac1-mediated ROS production to ameliorate blood-spinal cord barrier disruption in amyotrophic lateral sclerosis.}, journal = {Neurobiology of disease}, volume = {213}, number = {}, pages = {106987}, doi = {10.1016/j.nbd.2025.106987}, pmid = {40505784}, issn = {1095-953X}, mesh = {*Amyotrophic Lateral Sclerosis/metabolism/pathology ; Animals ; *rac1 GTP-Binding Protein/metabolism ; *Tissue Inhibitor of Metalloproteinase-1/metabolism/genetics ; *Spinal Cord/metabolism/pathology ; *Reactive Oxygen Species/metabolism ; Mice ; Endothelial Cells/metabolism ; Mice, Transgenic ; Humans ; Mice, Inbred C57BL ; Male ; Neuropeptides ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by the progressive degeneration of motor neurons, for which therapeutic strategies and pharmacological interventions remain limited. Disruption of the blood-spinal cord barrier (BSCB) has been identified as a significant factor that may exacerbate motor neuron damage. Tissue inhibitor of metalloproteinase-1 (TIMP1), a molecule known for its dual roles in inhibiting matrix metalloproteinase (MMP) activity and exerting cytokine-like effects via receptor interactions, has been demonstrated to ameliorate endothelial barrier damage in various diseases. Here, we explored the potential of TIMP1 to restore BSCB integrity as a strategy to slow the ALS progression. Specifically, the expression of TIMP1 or its mutant variant AlaTIMP1, which lacks MMP-inhibitory activity, in spinal cord microvascular endothelial cells (SCMECs) prior to disease onset significantly reduces BSCB leakage in mice with ALS, thereby alleviating motor function deficits and delaying disease progression. Additionally, TIMP1 expression restores the expression of junctional complexes in SCMECs, as demonstrated in both in vivo and in vitro ALS models. Mechanistic studies revealed that TIMP1 suppresses ALS injury-induced integrin β1 activation independent of MMP inhibition, blocking downstream Rac1 translocation to the membrane to form a complex with NOX2. The inhibition of NOX2 activity reduces ROS-induced cytoskeletal remodeling, consequently stabilizing overall junctional alignment and preserving the BSCB integrity. Overall, our findings elucidate an MMP-independent mechanism through which TIMP1 regulates BSCB integrity in ALS context, suggesting that TIMP1 could serve as a novel tool for the treatment of ALS, particularly for prophylactic treatment in patients with familial ALS.}, } @article {pmid40504748, year = {2025}, author = {Andersen, TM and Conde, B and Vollsæter, M}, title = {Seeing in Synchrony: Toward Personalized Noninvasive Ventilation in Amyotrophic Lateral Sclerosis Through Dynamic Upper-Airway Visualization.}, journal = {Respiratory care}, volume = {}, number = {}, pages = {}, doi = {10.1089/respcare.13193}, pmid = {40504748}, issn = {1943-3654}, } @article {pmid40504265, year = {2025}, author = {Torres-Villaros, H and Streho, M and Hoa, D and Giocanti-Aurégan, A}, title = {STARGUS: a comparative study of a new swept-source biometer and B-mode ultrasound in dense cataracts.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {}, number = {}, pages = {}, pmid = {40504265}, issn = {1435-702X}, support = {IIT #69445453//Alcon/ ; }, abstract = {PURPOSE: This study aimed to compare a new swept-source biometer to the gold standard B-mode ultrasound biometer for measuring the axial length (AL) when standard optical biometers failed due to cataract density.

METHODS: Patients with advanced cataracts whose AL could not be measured using optical biometers available in our clinics, including the Lenstar LS-900 and IOLMaster 500 and 700, were included. The AL, anterior chamber depth (ACD), and lens thickness (LT) were measured using a new swept-source biometer (SSB) (Argos[®], Alcon) and B-mode ultrasound. The Enhanced Retinal Visualization (ERV) mode of the new SSB was used when the standard mode did not provide reliable AL measurements.

RESULTS: AL measurements failed in 183 eyes due to cataract density using available biometers. The new SSB allowed successfully measuring the AL in 89.6% of cases, and the ERV mode was needed in 15.8% of eyes. The ALs measured with the new SSB and B-mode ultrasound were comparable, with an excellent intraclass correlation coefficient (ICC) of 0.99. No significant differences in ACD measurements were observed between new SSB and ultrasound or conventional biometers, with ICC of 0.81 and 0.87, respectively. However, the LT tended to be thinner with the new SSB compared to ultrasound, suggesting a potential source of error, but no significant difference was observed with conventional biometers (ICC of 0.88).

CONCLUSIONS: The new SSB Argos[®], in particular when the ERV mode is used, could be a reliable alternative to B-mode ultrasound for measuring AL in eyes with dense cataracts. It is as effective as ultrasound in measuring the AL, and it could help to improve cataract surgery planning and outcomes.}, } @article {pmid40503807, year = {2025}, author = {Rudnicki, SA and Al-Chalabi, A and Andrews, JA and Chio, A and Corcia, P and Couratier, P and Cudkowicz, ME and De Carvalho, M and Genge, A and Hardiman, O and Heiman-Patterson, T and Henderson, RD and Ingre, C and Johnston, W and Ludolph, A and Maragakis, NJ and Miller, TM and Mora, JS and Petri, S and Simmons, Z and Van Den Berg, LH and Zinman, L and Herder, KE and Kupfer, S and Malik, FI and Meng, L and Simkins, TJ and Wei, J and Wolff, AA and Shefner, JM and , }, title = {Hospitalizations as an outcome measure in COURAGE-ALS.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {}, number = {}, pages = {1-10}, doi = {10.1080/21678421.2025.2515907}, pmid = {40503807}, issn = {2167-9223}, abstract = {Objective: To describe the development of a methodology to characterize hospitalizations and their relationship to amyotrophic lateral sclerosis (ALS) and provide results using this process in a phase 3 trial of reldesemtiv in ALS. Methods: ALS clinical trialists assisted in developing a classification system to determine if a hospitalization was related to ALS (HR-ALS), unrelated (HU-ALS), or if the relationship was indeterminate (HI-ALS) and this was applied by the investigators to hospitalizations in COURAGE-ALS. Time to first hospitalization and number of hospitalizations were compared between those assigned reldesemtiv or placebo for up to 48 weeks. Demographic and clinical features were evaluated for prediction of hospitalization risk; this analysis was limited to those participants who completed the first 24-week double-blind placebo-controlled portion of the trial. Results: COURAGE-ALS terminated early due to futility. Time to first hospitalization was similar in the reldesemtiv compared to placebo arms as was the incidence, with 86 of the participants (17.6% of those originally assigned placebo and 18.0% originally on reldesemtiv) experiencing an event. The largest percentage of events was classified as HR-ALS for both placebo (64%, 18/28) and reldesemtiv (76%, 44/58). In a multivariate model, only bulbar or respiratory onset disease was a significant risk factor for hospitalization. Conclusion: While most hospitalizations in COURAGE-ALS were HR-ALS, HU-ALS and HI-ALS also occurred. When using hospitalization as an endpoint in an ALS clinical trial, recording its relationship to ALS provides additional details to characterize disease burden and clinical meaningfulness of the endpoint.}, } @article {pmid40502782, year = {2025}, author = {White, MA and Crowley, L and Massenzio, F and Li, X and Niblock, M and Coleman, MP and Barmada, SJ and Sreedharan, J}, title = {Inhibiting glycogen synthase kinase 3 suppresses TDP-43-mediated neurotoxicity in a caspase-dependent manner.}, journal = {Research square}, volume = {}, number = {}, pages = {}, pmid = {40502782}, issn = {2693-5015}, support = {/WT_/Wellcome Trust/United Kingdom ; R01 NS097542/NS/NINDS NIH HHS/United States ; R01 NS113943/NS/NINDS NIH HHS/United States ; R56 NS128110/NS/NINDS NIH HHS/United States ; }, abstract = {Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are progressive and ultimately fatal diseases characterised by 43-kDa TAR DNA-binding protein (TDP-43) pathology. Current disease modifying drugs have modest effects and novel therapies are sorely needed. We previously showed that deletion of glycogen synthase kinase-3 (GSK3) suppresses TDP-43-mediated motor neuron degeneration in Drosophila. Here, we investigated the potential of GSK3 inhibition to ameliorate TDP-43-mediated toxicity in mammalian neurons. Expression of TDP-43 both activated GSK3 and promoted caspase mediated cleavage of TDP-43. Conversely, GSK3 inhibition reduced the abundance of full-length and cleaved TDP-43 in neurons expressing wild-type or disease-associated mutant TDP-43, ultimately ameliorating neurotoxicity. Our results suggest that TDP-43 turnover is promoted by GSK3 inhibition in a caspase-dependent manner, and that targeting GSK3 activity has therapeutic value.}, } @article {pmid40502095, year = {2025}, author = {Poch, D and Mukherjee, C and Mallik, S and Todorow, V and Kuiper, EFE and Dhingra, N and Surovtseva, YV and Schlieker, C}, title = {Integrative Chemical Genetics Platform Identifies Condensate Modulators Linked to Neurological Disorders.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2025.06.07.658469}, pmid = {40502095}, issn = {2692-8205}, abstract = {UNLABELLED: Aberrant biomolecular condensates are implicated in multiple incurable neurological disorders, including Amyotrophic Lateral Sclerosis (ALS), Frontotemporal Dementia (FTD), and DYT1 dystonia. However, the role of condensates in driving disease etiology remains poorly understood. Here, we identify myeloid leukemia factor 2 (MLF2) as a disease-agnostic biomarker for phase transitions, including stress granules and nuclear condensates associated with dystonia. Exploiting fluorophore-derivatized MLF2 constructs, we developed a high-content platform and computational pipeline to screen modulators of NE condensates across chemical and genetic space. We identified RNF26 and ZNF335 as protective factors that prevent the buildup of nuclear condensates sequestering K48-linked polyubiquitinated proteins. Chemical screening identified four FDA-approved drugs that potently modulate condensates by resolving polyubiquitinated cargo and MLF2 accumulation. Our exploratory integrated chemical-genetics approach suggests that modulation of zinc, and potentially autophagy and oxidative stress, is critical for condensate modulation and nuclear proteostasis, offering potential therapeutic strategies for neurological disorders. Application of our platform to a genome-wide CRISPR KO screen identified strong enrichment of candidate genes linked to primary microcephaly and related neurodevelopmental disorders. Two hypomorphic microcephaly-associated alleles of ZNF335 failed to rescue nuclear condensate accumulation in ZNF335 KO cells, suggesting that aberrant condensates and impaired nuclear proteostasis may contribute to the pathogenesis of microcephaly.

HIGHLIGHTS: MLF2 emerges as a disease-agnostic condensate biomarker co-localizing with TDP-43 and G3BP1FDA-approved drugs target condensates linked to perturbed proteostasis.RNF26 and ZNF335 are identified as modulators of nuclear phase transitions.Microcephaly patient disease alleles fail to counteract aberrant condensates.}, } @article {pmid40501612, year = {2025}, author = {Bhuiyan, P and Yi, Y and Wei, B and Yan, A and Dong, L and Wei, H}, title = {Intranasal Dantrolene Nanoparticles for Treatment of Amyotrophic Lateral Sclerosis as a Disease-Modifying Drug.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2025.05.21.655232}, pmid = {40501612}, issn = {2692-8205}, abstract = {Calcium dysregulation, caused by pathological activation of ryanodine receptors, contributes to motor neuron degeneration, motor dysfunction, and muscle weakness in SOD1-G93A transgenic amyotrophic lateral sclerosis (ALS) mice. This study investigates the therapeutic efficacy of intranasally administered dantrolene nanoparticles, a ryanodine receptor antagonist, on motor neuron function, muscle strength, spinal cord degeneration, and survival outcomes. Male and female C57BL/6SJLF1 non-transgenic control and SOD1-G93A ALS transgenic mice were assigned to one of three experimental groups: 1) NO TX: No treatment control; 2) IN-DAN: Intranasal administration of dantrolene in the Ryanodex formulation vehicle (RFV), at a dosage of 5mg/kg, administered daily from ages 90-120 days; 3) IN-VEH: Intranasal administration of RFV alone (as a vehicle control), following the same dosing schedule as the IN-DAN condition. Body weight and general motor function were monitored weekly, with survival recorded daily throughout the treatment period. At the treatment conclusion, neurological function was comprehensively evaluated using a standardized neurological scoring system. Motor coordination and balance were assessed using the balance beam test (beam widths of 12 mm and 6 mm) and the rotarod test. Muscle strength was evaluated by measuring grip force using the Kondziela inverted screen test. After behavioral testing, spinal cord tissues were collected for analysis. The levels of neurofilament light chain (NFL), a skeletal neuron protein, and spinal cord weight were determined to measure spinal cord degeneration. Compared to non-transgenic control mice, SOD1-G93A mice exhibited significantly elevated neurological scores, indicating severely impaired neurological function. This deterioration was robustly and significantly ameliorated by IN-DAN treatment by 90% (P<0.0001). Similarly, ALS mice demonstrated impairments in motor coordination and balance on the beam balance test, with dramatic and significant increases in crossing time and the number of foot slips. These impairments were greatly and significantly mitigated by IN-DAN treatment, by 78% in crossing time (P<0.0001) and 84% in the number of slips (P<0.0001) on the 12 mm-wide beam, but not by the vehicle control. ALS mice demonstrated progressive body weight loss as well, which was similarly reversed by IN-DAN treatment, but not by the vehicle control. Muscle strength, as measured by grip force, was significantly reduced in ALS mice but robustly preserved IN-DAN treatment, which prevented the decrease by 213% (P<0.0001), while the vehicle control had no effect. Spinal cord weight was significantly reduced in ALS mice, a trend reversed by intranasal dantrolene nanoparticle treatment, but not by the vehicle control. Survival analysis revealed that 100% of control mice survived through the 30-day treatment period (up to 120 days of age), while survival in untreated or vehicle-treated ALS mice dropped to 67%. In contrast, ALS mice treated with intranasal dantrolene nanoparticles demonstrated a significantly improved survival rate of 89%. Thus, intranasal dantrolene nanoparticle treatment significantly and robustly improved neurological outcomes in SOD1-G93A ALS mice, inhibiting neurological impairment, motor dysfunction, balance deficits, and muscle weakness. These improvements were associated with a marked inhibition of spinal cord weight loss. Additionally, dantrolene treatment reversed body weight loss and significantly improved survival probability in ALS mice.}, } @article {pmid40501554, year = {2025}, author = {Trautwig, AN and Shantaraman, A and Chung, M and Dammer, EB and Ping, L and Duong, DM and Petrucelli, L and Ward, ME and Glass, JD and Nelson, PT and Levey, AI and McEachin, ZT and Seyfried, NT}, title = {Molecular subtyping based on hippocampal cryptic exon burden reveals proteome-wide changes associated with TDP-43 pathology across the spectrum of LATE and Alzheimer's Disease.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {40501554}, issn = {2692-8205}, support = {P01 NS084974/NS/NINDS NIH HHS/United States ; P30 AG066511/AG/NIA NIH HHS/United States ; R01 NS132330/NS/NINDS NIH HHS/United States ; U01 AG061357/AG/NIA NIH HHS/United States ; }, abstract = {TDP-43 pathology is a defining feature of Limbic-Predominant Age-Related TDP-43 Encephalopathy neuropathologic change (LATE-NC) and is frequently comorbid with Alzheimer's disease neuropathologic change (ADNC). However, the molecular consequences of co-occurring LATE-NC and ADNC pathology (TDP-43, β-amyloid, and tau protein pathologies) remain unclear. Here, we conducted a comparative biochemical, molecular, and proteomic analysis of hippocampal tissue from 90 individuals spanning control, LATE-NC, ADNC, and ADNC+LATE-NC groups to assess the impact of cryptic exon (CE) inclusion, phosphorylated TDP-43 pathology (pTDP-43), and AD-related pathologies (β-amyloid, and tau) on the proteome. ADNC+LATE-NC cases exhibited the highest burden of CE inclusion as quantified by measuring the levels of known TDP-43 regulated CEs within eight transcripts: STMN2, UNC13A, ELAVL3, KALRN, ARHGAP32, CAMK2B, PFKP, and SYT7. While CE levels correlated with pTDP-43 pathology, they were more strongly correlated with each other, suggesting that the molecular signature of CE inclusion may serve as a more sensitive measure of TDP-43 dysfunction than pTDP-43 pathology alone. Unbiased classification based on the relative abundance of these eight CEs stratified individual cases into low, intermediate, and high CE burden subtypes, largely independent of β-amyloid and tau pathology. Proteome-wide correlation analysis revealed a bias toward reduced protein levels from genes harboring TDP-43-regulated CEs in cases with high cumulative CE burden. Notably, proteins significantly decreased under high CE burden included canonical STMN2, ELAVL3, and KALRN, as well as kinesin proteins that are genetically associated with amyotrophic lateral sclerosis. Co-expression network analysis identified both shared and distinct biological processes across CE subtypes and pathways associated with pTDP-43, tau, β-amyloid pathologies, and CE accumulation in the hippocampus. Protein modules associated with TDP-43 loss of function were prioritized by integrating proteomic data from TDP-43-depleted human neurons with the hippocampal co-expression network. Specifically, we observed decreased endosomal vesicle, microtubule-binding, and synaptic modules, alongside an increase in RNA-binding modules. These results provide new insights into the proteomic impact of CE burden across the spectrum of LATE and AD pathological severity, highlighting the molecular consequences of TDP-43 dysfunction in neurodegenerative disease.}, } @article {pmid40501419, year = {2025}, author = {Bischoff, KE and Kojimoto, G and O'Riordan, DL and Leavell, YL and Maiser, S and Grouls, A and Smith, AK and Pantilat, SZ and Kluger, BM and Mehta, AK}, title = {Strengths and Opportunities: Clinicians' Perspectives on Palliative Care for Amyotrophic Lateral Sclerosis (ALS) in the United States.}, journal = {Muscle & nerve}, volume = {72}, number = {3}, pages = {455-463}, pmid = {40501419}, issn = {1097-4598}, support = {/AG/NIA NIH HHS/United States ; //ALS Association/ ; /AG/NIA NIH HHS/United States ; }, mesh = {*Amyotrophic Lateral Sclerosis/therapy/epidemiology/psychology ; Humans ; *Palliative Care/methods ; United States/epidemiology ; Male ; Female ; *Attitude of Health Personnel ; Surveys and Questionnaires ; Middle Aged ; }, abstract = {INTRODUCTION/AIMS: Little is known about the state of palliative care (PC) for people with ALS (pALS) in the U.S. We aimed to examine current practice regarding PC for pALS and how it can be improved.

METHODS: ALS and PC clinicians completed surveys about: (1) strengths and limitations of PC for pALS provided by ALS and PC teams, (2) reasons for and barriers to referring to specialty PC, and (3) how PC could be improved.

RESULTS: One hundred forty-one ALS clinicians from 72 institutions and 242 PC clinicians from 96 institutions in 30 states completed surveys. Half of ALS clinicians reported they are able to manage patients' pain (55%) and mood symptoms (52%) "very well." Fewer reported managing care partner needs (43%) and spiritual/existential distress (29%) "very well." Fifty-eight percent of pALS are referred to outpatient PC and 69% to hospice at some point in the illness. Barriers to referring include that PC programs are not sufficiently available to pALS. ALS clinicians generally felt satisfied with PC teams' care, but PC clinicians were less confident managing motor symptoms (51% confident) and helping care partners understand how to provide care (51%) and use equipment (25%). Most clinicians felt the quality of PC provided by ALS (77%) and PC (90%) teams is good/excellent. However, qualitative comments highlighted that both ALS and PC clinicians have knowledge gaps, and collaboration between ALS and PC clinicians should increase.

DISCUSSION: Clinician education, expansion of PC services, strengthened collaboration, and further research about PC for pALS are needed.}, } @article {pmid40500504, year = {2025}, author = {Niu, J and Verkhratsky, A and Butt, A and Yi, C}, title = {Oligodendroglia in Ageing and Age-Dependent Neurodegenerative Diseases.}, journal = {Advances in neurobiology}, volume = {43}, number = {}, pages = {363-405}, pmid = {40500504}, issn = {2190-5215}, mesh = {Humans ; *Oligodendroglia/pathology/physiology/metabolism ; *Neurodegenerative Diseases/pathology/physiopathology/metabolism ; *Aging/pathology/physiology ; Animals ; }, abstract = {The central nervous system is susceptible to gradual decline with age, affecting all types of glial cells in the process. Compared to other glial cells, the oligodendroglial lineage is highly vulnerable to ageing and undergoes significant characteristic changes that impact upon its structure and impair its physiological functions. Therefore, the ageing and degeneration of oligodendroglia become major risk factors for neurodegenerative diseases. During the age-related disease process, changes in oligodendroglia lead to a decline in their ability to regenerate myelin and respond to the aged microenvironment, which are closely linked to the pathogenesis of neurodegenerative diseases, facilitating the emergence of these diseases in older populations. In this chapter, we introduce the physiological changes of oligodendroglia during ageing and the related mechanisms and then summarise their pathophysiological contributions to age-related cognitive disorders. Finally, we discuss potential therapeutic strategies that target oligodendroglia for future research on neurodegenerative diseases.}, } @article {pmid40499018, year = {2025}, author = {Yadav, V and Singh, R and Chaturvedi, M and Siddhanta, S and Chaturvedi, R}, title = {Multivariate and Machine Learning-Derived Virtual Staining and Biochemical Quantification of Cancer Cells through Raman Hyperspectral Imaging.}, journal = {Analytical chemistry}, volume = {97}, number = {24}, pages = {12660-12668}, doi = {10.1021/acs.analchem.5c01028}, pmid = {40499018}, issn = {1520-6882}, mesh = {*Spectrum Analysis, Raman/methods ; Humans ; *Machine Learning ; Principal Component Analysis ; Multivariate Analysis ; Neural Networks, Computer ; *Hyperspectral Imaging/methods ; Staining and Labeling ; Least-Squares Analysis ; Lipids/analysis ; Algorithms ; Collagen/analysis ; Cell Line, Tumor ; }, abstract = {Advances in virtual staining and spatial omics have revolutionized our ability to explore cellular architecture and molecular composition with unprecedented detail. Virtual staining techniques, which rely on computational algorithms to map molecular or structural features, have emerged as powerful tools to visualize cellular components without the need for physical dyes, thereby preserving sample integrity. Similarly, spatial omics enable the mapping of biomolecules across tissue or cell surfaces, providing spatially resolved insights into biological processes. However, traditional dye-based staining methods, while widely used, come with significant limitations. In this context, Raman spectroscopy offers a robust, label-free alternative for probing molecular composition at a high resolution. We present a novel algorithm that reconstructs super-resolved Raman images by extracting spectral patterns from surrounding pixels, enabling detailed, label-free visualization of cellular structures. By employing Raman spectroscopy in conjunction with chemometric tools such as principal component analysis (PCA), multivariate curve resolution-alternating least squares (MCR-ALS), and artificial neural network (ANN), we performed a quantitative analysis of key biomolecular components, including collagen, lipids, glycogen, and nucleic acids, and classify the different cancer cell lines with an accuracy of nearly 99%. This approach not only enabled the identification of distinct molecular fingerprints across the different cancer types but also provided a powerful tool for understanding the biochemical variations that underlie tumor heterogeneity. This innovative combination of virtual staining, spatial omics, and advanced chemometrics highlights the potential for more accurate diagnostics and personalized treatment strategies in oncology.}, } @article {pmid40498717, year = {2025}, author = {Komolafe, OO and Mustofa, J and Daley, MJ and Walton, D and Tawiah, A}, title = {Current applications and outcomes of AI-driven adaptive learning systems in physical rehabilitation science education: A scoping review protocol.}, journal = {PloS one}, volume = {20}, number = {6}, pages = {e0325649}, pmid = {40498717}, issn = {1932-6203}, mesh = {Scoping Review as Topic ; Humans ; *Artificial Intelligence ; *Rehabilitation/education ; *Learning ; }, abstract = {Rationale Integrating artificial intelligence (AI) into education has introduced transformative possibilities, particularly through adaptive learning systems. Rehabilitation science education stands to benefit significantly from the integration of AI-driven adaptive learning systems. However, the application of these technologies remains underexplored. Understanding the current applications and outcomes of AI-driven adaptive learning in broader healthcare education can provide valuable insights into how these approaches can be effectively adapted to enhance multimodal case-based learning in Rehabilitation Science education. Methods The scoping review is based on the Joanne Briggs Institute (JBI) framework. It is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRIMSA-ScR). A comprehensive search strategy will be used to find relevant papers in Scopus, PubMed, CINAHL, Education Resources Information Center (ERIC), Association for Computing Machinery (ACM), ProQuest Education Journal, Web of Science, ProQuest Dissertations & Theses Global, and IEEE Digital Library. This review will include all types of studies that describe or evaluate our outcomes of interest: AI models used, learning and teaching methods, effective implementation, outcomes, and challenges of ALS's in rehabilitation health science education. Data will be extracted using a pre-piloted data extraction sheet and synthesized narratively to identify themes and patterns. Discussion This scoping review will synthesize the applications of AI models in rehabilitation science education. It will provide evidence for educators, healthcare professionals, and policymakers to incorporate AI into educational curricula effectively. The protocol is registered on Open Science Framework registries at https://osf.io/e46s3.}, } @article {pmid40498122, year = {2025}, author = {Doronzio, PN and Lattante, S and Bernardo, D and Patanella, AK and Bisogni, G and Meleo, E and Del Giudice, E and Colavito, D and Porro, LM and Sabatelli, E and Conte, A and Zollino, M and Sabatelli, M and Marangi, G}, title = {Burden of pathogenetic and likely pathogenetic variants in SPG7, SPG11 and AP4 genes in Amyotrophic Lateral Sclerosis. A case-control study.}, journal = {Journal of neurology}, volume = {272}, number = {7}, pages = {455}, pmid = {40498122}, issn = {1432-1459}, support = {Linea D1//Catholic University of Sacred Hearth/ ; Linea D1//Catholic University of Sacred Hearth/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics ; Male ; Female ; Middle Aged ; Case-Control Studies ; Aged ; Adult ; *Genetic Predisposition to Disease/genetics ; *Adaptor Protein Complex 4/genetics ; *Proteins/genetics ; Spastic Paraplegia, Hereditary/genetics ; Genetic Variation/genetics ; ATPases Associated with Diverse Cellular Activities ; Metalloendopeptidases ; }, abstract = {BACKGROUND: There is evidence that some Hereditary Spastic Paraplegia (HSP) genes are linked to Amyotrophic Lateral Sclerosis (ALS). In particular, KIF5A and SPG11 genes, which cause two different forms of HSP, are also associated with adult-onset and Juvenile ALS, respectively.

OBJECTIVES: To study the frequencies of pathogenetic and likely pathogenetic variants in HSP genes in ALS patients and to determine whether they act as predisposing factors.

METHODS: We analysed 72 HSP-associated genes in 1024 ALS and 44 Primary Lateral Sclerosis patients and applied customized ACMG criteria to identify pathogenic and likely pathogenic variants. Based on the frequency of identified variants, six genes, including SPG7, SPG11 and the four genes encoding the subunits of the AP4 adaptor protein, were selected for analysis in an additional cohort of 481 ALS patients. Overall results on 1549 patients were compared with 1138 controls.

RESULTS: The frequency of variants in SPG7 gene was 0.45% (7/1549) in patients vs 0.18% (2/1138) in controls (p = 0.19), in SPG11 was 0.77% (12/1549) in cases and 0.26% (3/1138) in controls (p = 0.06), in AP4 genes was 0.64% (10/1549) in patients and 0.26% (3/1138) in controls (p = 0.13). The total number of variants detected across SPG7, SPG11 and AP4 genes was statistically different between patients and controls (1.87% vs 0.7%; p = 0.006).

CONCLUSIONS: We found a significant enrichment of variants in a set of HSP genes, including SPG7, SPG11 and AP4 genes, in a large cohort of ALS patients, suggesting that they may act as predisposing factors for ALS.}, } @article {pmid40498024, year = {2025}, author = {Pisoni, L and Donini, L and Gagni, P and Pennuto, M and Ratti, A and Verde, F and Ticozzi, N and Mandrioli, J and Calvo, A and Basso, M}, title = {Barriers in the Nervous System: Challenges and Opportunities for Novel Biomarkers in Amyotrophic Lateral Sclerosis.}, journal = {Cells}, volume = {14}, number = {11}, pages = {}, pmid = {40498024}, issn = {2073-4409}, support = {MUR PNRR project iNEST - Interconnected Nord-Est Innovation Ecosystem (ECS00000043)//NextGenerationEU/ ; PERMEALS - PNRR-MAD-2022-12375731//Ministero della Salute/ ; CUP E53D23019700001, project "MYSTICALS"//European Union - Next Generation EU, Mission 4, Component 1/ ; RF-2016-02361616//Ministero della Salute/ ; EVTestInALS//AriSLA/ ; Aldo Ravelli Center for Neurotechnology and Experimental Brain Therapeutics//Università degli Studi di Milano/ ; MUR-PRIN 2022 project EV-PRINT 2022CS9H53//Next Generation EU/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism/pathology/diagnosis ; *Biomarkers/metabolism ; Extracellular Vesicles/metabolism ; Animals ; }, abstract = {Amyotrophic Lateral Sclerosis (ALS) is a complex neurodegenerative disorder characterized by wide phenotypic heterogeneity. Despite efforts to carefully define and stratify ALS patients according to their clinical and genetic features, prognosis prediction still remains unreliable. Biomarkers that reflect changes in the central nervous system would be useful, but the physical impossibility of direct sampling and analysis of the nervous system makes them challenging to validate. A highly explored option is the identification of neuronal-specific markers that could be analyzed in peripheral biofluids. This review focuses on the description of the physical and biological barriers to the central nervous system and of the composition of biofluids in which ALS disease biomarkers are actively searched. Finally, we comment on already validated biomarkers, such as the neurofilament light chain, and show the potential of extracellular vesicles (EVs) and cell-free DNA as additional biomarkers for disease prediction.}, } @article {pmid40497426, year = {2025}, author = {Bao, J and Zhou, J and Xie, Z and Zou, M and Napier, R and Li, J}, title = {CYP99A2 from Aegilops tauschii metabolizes pyroxsulam but not mesosulfuron-methyl, causing different natural sensitivity to two herbicides.}, journal = {Pest management science}, volume = {}, number = {}, pages = {}, doi = {10.1002/ps.8967}, pmid = {40497426}, issn = {1526-4998}, support = {2021YFD1700100//National Key Research and Development Program/ ; }, abstract = {BACKGROUND: Weed tolerance to herbicides poses a major threat to agricultural production. Aegilops tauschii has promising prospects for genetic development; however, the fact that this plant is invasive in China and other countries is often ignored owing to its pronounced adaptability. Among the current acetolactate synthase (ALS) inhibitors, only mesosulfuron-methyl (MM) can control A. tauschii, and pyroxsulam (P) is ineffective. However, a knowledge gap remains regarding differences in sensitivity of A. tauschii to these two ALS inhibitors.

RESULTS: We hypothesized that differences in sensitivity of A. tauschii to the ALS inhibitors MM and P are mediated by metabolic enzymes. Whole-plant experiments showed that the P450s inhibitor 1-Aminobenzotriazole (ABT) significantly increased the sensitivity of A. tauschii to P compared with MM. In A. tauschii, the P metabolism rate was higher than that of MMl, as detected by liquid chromatography with tandem mass spectrometry. Transcriptome sequencing and quantitative real-time polymerase chain reaction identified seven differentially expressed P450s after P and MM treatments, three of which were upregulated after P treatment and were unaffected by MM. AtCYP99A2 reduced plant sensitivity to P by metabolizing P without affecting MM by overexpressing it in Arabidopsis and inducing in vitro protein expression.

CONCLUSION: To the best of our knowledge, this is the first report on P450 involvement in A. tauschii sensitivity to two ALS-inhibitor herbicides. This study deepens current understandings of A. tauschii and facilitates subsequent screening of specific metabolic enzyme inhibitors to be used as synergists in combination with herbicides, which will provide new avenues for weed control. © 2025 Society of Chemical Industry.}, } @article {pmid40496636, year = {2025}, author = {Qiao, H and Cheng, X and Tian, H and Zhao, C and Sun, X and Zhao, J}, title = {Lower cervical C6/C7 andersson lesion with upper cervical C1/C2 fracture in ankylosing spondylitis: a case report and literature review.}, journal = {Frontiers in surgery}, volume = {12}, number = {}, pages = {1568553}, pmid = {40496636}, issn = {2296-875X}, abstract = {Cervical andersson lesions (ALs) are rare in patients with ankylosing spondylitis (AS), and even more rare in patients with simultaneous superior cervical atlantoaxial fracture and dislocation. Here, we present a case of C1 Jefferson fracture (C1 bilateral posterior arch fracture), C2 odontoid, lateral mass, vertebral fracture (nonclassic C2 hangman fracture), traumatic posterior atlantoaxial dislocation (AAD) and C6/C7 AL in a long-standing AS cervical spine. The patient with traumatic AS-related cervical fractures underwent a two-stage surgery. The stage I surgery involved a posterior atlantoaxial reduction and fixation surgery combined with C5/C6/T1/T2 posterior pedicle screw fixation plus C6/C7 decompression. One week later, C6/C7 anterior cervical corpectomy decompression and fusion (ACCF) with long anterior plate stabilization combined with iliac crest bone graft transplantation was performed for stage II surgery. The patient recovery observed during follow-up was satisfactory. Nine-month postoperative radiological images revealed fracture union of the upper and lower cervical spine with optimal reduction of the atlantoaxial segment. In conclusion, lower cervical ALs with simultaneous upper cervical C1/C2 fractures in the AS are very rare. Posterior C1-C2 fixation combined with C6-C7 AL corpectomy/fusion and posterior pedicle screw fixation may offer a desirable alternative approach for this complex case of cervical trauma. During treatment, complete decompression, effective reduction, and potent stabilization can comprehensively improve the clinical prognosis.}, } @article {pmid40496269, year = {2025}, author = {Liu, QZ and Zeng, L and Sun, NZ}, title = {Linguistic exclusion in orthopedic research: Cultural adaptation, multilingual innovations, and pathways to global health equity.}, journal = {World journal of orthopedics}, volume = {16}, number = {5}, pages = {106951}, pmid = {40496269}, issn = {2218-5836}, abstract = {This editorial critically evaluated the recent study by AlMousa et al, which examined the impact of the Arabic version of the American Academy of Orthopedic Surgeons Foot and Ankle Outcomes Questionnaire (AAOS-FAOQ) on postoperative quality of life and recovery in Arabic-speaking patients with traumatic foot and ankle injuries. In the context of systemic linguistic exclusion in orthopedic research-where English-language journals dominated most publications and non-English-speaking populations faced dual barriers of trial underrepresentation and semantic distortions (e.g., mistranslations of terms like "joint instability" in Arabic)-AlMousa et al's work highlighted the transformative potential of culturally adapted methodologies. Their rigorous four-stage adaptation framework validated the Arabic AAOS-FAOQ as a reliable tool, enhancing ecological validity and reducing bias in patient-reported outcomes. However, limitations such as regional specificity (Gulf-centric sampling) and short follow-up periods (4 months) underscored broader challenges in non-English research: Redundant studies, prolonged hospital stays for limited English proficiency patients, and underrepresentation of certain ethnic groups in trials. To dismantle linguistic hegemony, we proposed semantic reconstruction (e.g., integrating culturally specific indicators like "prayer posture"), dialect-aware neural translation, and World Health Organization led terminology standardization. In line with these proposed solutions, AlMousa et al's study exemplified how language-sensitive adaptations could bridge equity gaps, while future efforts would need to balance cultural specificity with cross-study comparability through AI-driven multilingual databases and policy mandates for cultural adaptation roadmaps.}, } @article {pmid40496257, year = {2025}, author = {Ding, LH and Wu, PF and Sun, NZ}, title = {Investigation of clinical outcomes in conservative management of hook fractures: Commentary on recent findings.}, journal = {World journal of orthopedics}, volume = {16}, number = {5}, pages = {106881}, pmid = {40496257}, issn = {2218-5836}, abstract = {This editorial critically evaluates the landmark study by Tanaka and Yoshii, which demonstrated a 100% union rate with conservative management of hamate hook fractures, challenging the historical preference for surgical intervention. In contrast to Scheufle et al's report of 90%-100% failure rates with early surgical approaches, Tanaka and Yoshii's protocol achieved universal healing despite delayed diagnoses in 25% of cases. Central to this success is the systematic integration of high-resolution computed tomography for early diagnosis and dynamic monitoring of trabecular bone regeneration, significantly reducing missed diagnoses and guiding personalized immobilization timelines. The patient-centered strategy-allowing temporary splint removal during low-risk activities-balanced fracture stability with joint mobility preservation, avoiding post-treatment stiffness. However, limitations such as small sample size (n = 16), selection bias, and insufficient long-term functional data (e.g., grip strength, return-to-sport metrics) underscore the need for comparative trials. Emerging trends, including adjunct therapies like low-intensity pulsed ultrasound and biologics (e.g., teriparatide), are proposed to accelerate healing while minimizing immobilization risks. This work redefines conservative fracture management paradigms, emphasizing innovation without compromising efficacy. Overall, this assessment deepens our understanding of the conservative management of hook fractures and provides evidence-based insights for improved clinical decision-making.}, } @article {pmid40495844, year = {2025}, author = {Byeon, H}, title = {Unveiling the invisible: How cutting-edge neuroimaging transforms adolescent depression diagnosis.}, journal = {World journal of psychiatry}, volume = {15}, number = {5}, pages = {102953}, pmid = {40495844}, issn = {2220-3206}, abstract = {Yu et al's study has advanced the understanding of the neural mechanisms underlying major depressive disorder (MDD) in adolescents, emphasizing the significant role of the amygdala. While traditional diagnostic methods have limitations in objectivity and accuracy, this research demonstrates a notable advancement through the integration of machine learning techniques with neuroimaging data. Utilizing resting-state functional magnetic resonance imaging (fMRI), the study investigated functional connectivity (FC) in adolescents with MDD, identifying notable reductions in regions such as the left inferior temporal gyrus and right lingual gyrus, alongside increased connectivity in Vermis-10. The application of support vector machines (SVM) to resting-state fMRI (rs-fMRI) data achieved an accuracy of 83.91%, sensitivity of 79.55%, and specificity of 88.37%, with an area under the curve of 0.6765. These results demonstrate how SVM analysis of rs-fMRI data represents a significant improvement in diagnostic precision, with reduced FC in the right lingual gyrus emerging as a particularly critical marker. These findings underscore the critical role of the amygdala in MDD pathophysiology and highlight the potential of rs-fMRI and SVM as tools for identifying reliable neuroimaging biomarkers.}, } @article {pmid40495464, year = {2025}, author = {Majtan, T and Mijatovic, E and Petrosino, M}, title = {Understanding the Impact of Mutations in the Cystathionine Beta-Synthase Gene: Towards Novel Therapeutics for Homocystinuria.}, journal = {Molecular and cellular biology}, volume = {45}, number = {8}, pages = {327-342}, doi = {10.1080/10985549.2025.2511338}, pmid = {40495464}, issn = {1098-5549}, mesh = {Humans ; *Homocystinuria/genetics/drug therapy/enzymology ; *Cystathionine beta-Synthase/genetics/metabolism/chemistry ; Animals ; *Mutation ; Protein Folding ; Molecular Chaperones/therapeutic use ; }, abstract = {Protein misfolding and conformational instability drive protein conformational disorders, causing either accelerated degradation and loss-of-function, as in inherited metabolic disorders like lysosomal storage disorders, or toxic aggregation and gain-of-function, as in neurodegenerative diseases like Alzheimer's disease or amyotrophic lateral sclerosis. Classical homocystinuria (HCU), an inborn error of sulfur amino acid metabolism, results from cystathionine beta-synthase (CBS) deficiency. CBS regulates methionine conversion into metabolites critical for redox balance (cysteine, glutathione) and signaling (H2S). Pathogenic missense mutations in the CBS gene often impair folding, cofactor binding, stability or oligomerization rather than targeting the key catalytic residues of the CBS enzyme. Advances in understanding of CBS folding and assembly as well as CBS interactions with cellular proteostasis network offer potential for therapies using pharmacological chaperones (PCs), i.e., compounds facilitating proper folding, assembly or cellular trafficking. This review discusses progress in identifying PCs for HCU, including chemical chaperones, cofactors, and proteasome inhibitors. We outline future directions, focusing on high-throughput screening and structure-based drug design to develop CBS-specific PCs. These could stabilize mutant CBS, enhance its stability and restore activity, providing new treatments for HCU and possibly other conditions related to dysregulated CBS, such as cancer or Down's syndrome.}, } @article {pmid40495157, year = {2025}, author = {Gonsalves, GS}, title = {Still we rise: research on bias and discrimination will endure.}, journal = {International journal for equity in health}, volume = {24}, number = {1}, pages = {167}, pmid = {40495157}, issn = {1475-9276}, mesh = {Humans ; Racism ; Boston ; *Prejudice ; United States ; *Social Discrimination ; *Vaping/epidemiology ; Smoking/epidemiology ; Bias ; Sexism ; }, abstract = {This is a commentary on Reisner et al's Analyzing multiple types of discrimination using implicit and explicit measures, comparing target vs. Dominant groups, in a study of smoking/vaping among community health center members in Boston, Massachusetts (2020-2022). This manuscript is a study of the intersection of multiple forms of discrimination-racism, sexism, heterosexism, cissexism, ageism, and sizeism-and measures of implicit and explicit bias in the context of current smoking and vaping behavior among patients from targeted versus dominant groups at community health centers in Boston, Massachusetts (USA) from 2020 to 2022. The authors used logistic regression to assess smoking and vaping behavior with each type of discrimination, and then extended this analysis employing a meta-regression approach to better understand relationships across all types of discrimination under consideration in their study. Recently, the grant from the US National Institutes of Health, which supported this research was terminated in progress for ideological reasons by the current US administration under President Donald J. Trump for simply focusing on discrimination. While this study was among the first to be terminated by the Trump administration, hundreds of grants from the NIH and other US research funders have been cancelled in the first half of 2025. Reisner et al's paper is an important piece of research, but it represents the start of a sophisticated inquiry into discrimination and bias, and future work by this team and in this area of research is necessary and sadly, now impossible to do with federal scientific funding. Work on discrimination and bias has always faced obstacles, but the scope and scale of attacks on science in the US require all scientists to push back against this censorship and political interference in the funding and conduct of research.}, } @article {pmid40494757, year = {2025}, author = {Luu, S and McGuiness, O and Menadue, C and Piper, AJ and Wong, K and Yee, BJ and Gray, EL}, title = {Inter-Night Variability of Nocturnal Pulse Oximetry in People Living With Motor Neuron Disease: A Retrospective Observational Study.}, journal = {Respirology (Carlton, Vic.)}, volume = {}, number = {}, pages = {}, doi = {10.1111/resp.70072}, pmid = {40494757}, issn = {1440-1843}, abstract = {BACKGROUND AND OBJECTIVE: Nocturnal pulse oximetry (NPO) is a simple and inexpensive assessment tool that has previously been shown to correlate with prognosis and timing of non-invasive ventilation (NIV) initiation in people living with motor neuron disease (plwMND). However, the optimal number of nights for measuring NPO has not been defined for this population, with other respiratory conditions exhibiting both low and high night-to-night variability in NPO parameters. This study aims to determine the inter-night variability in NPO data over three nights in plwMND.

METHODS: We conducted a retrospective analysis of 132 studies in which plwMND underwent three consecutive nights of NPO. Intraclass correlation coefficients (ICC) were used to assess the reliability of key NPO parameters, including mean percentage of total recording time with oxygen saturation (SpO2) < 90% (T90), oxygen desaturation index (ODI), basal SpO2 and nadir SpO2. The proportion of plwMND meeting NIV criteria based on single-night versus multi-night assessments was also compared.

RESULTS: Excellent reliability was observed for T90 (ICC(1) = 0.940) and ODI (ICC(1) = 0.901), while basal SpO2 (ICC(1) = 0.845) and nadir SpO2 (ICC(1) = 0.768) demonstrated good reliability. However, relying on a single-night NPO assessment failed to identify 12% of plwMND who met NIV criteria when evaluated over three nights.

CONCLUSION: Despite good to excellent inter-night variability of NPO data in plwMND, multi-night NPO monitoring improves the accuracy of identifying plwMND requiring NIV. These findings support the need for multi-night assessments to enhance clinical decision-making in MND management.}, } @article {pmid40493571, year = {2025}, author = {Nathan Kochen, N and Murray, M and Zafari, S and Vunnam, N and Liao, EE and Chen, L and Braun, AR and Sachs, JN}, title = {Fluorescence Lifetime-Based FRET Biosensors for Monitoring N Terminal Domain-Dependent Interactions of TDP-43 in Living Cells: A Novel Approach for ALS and FTD Drug Discovery.}, journal = {ACS chemical neuroscience}, volume = {16}, number = {13}, pages = {2450-2462}, pmid = {40493571}, issn = {1948-7193}, mesh = {Humans ; *Biosensing Techniques/methods ; *Fluorescence Resonance Energy Transfer/methods ; *DNA-Binding Proteins/metabolism/genetics ; *Frontotemporal Dementia/metabolism/drug therapy ; *Amyotrophic Lateral Sclerosis/metabolism/drug therapy ; *Drug Discovery/methods ; Animals ; Ketoconazole/pharmacology ; High-Throughput Screening Assays ; HEK293 Cells ; Caenorhabditis elegans ; }, abstract = {Pathological aggregates of TDP-43 are implicated in Alzheimer's disease, frontotemporal dementia, and amyotrophic lateral sclerosis. While therapeutic efforts have traditionally focused on mitigating end-stage TDP-43 aggregation, recent evidence highlights an upstream and potentially targetable event: the loss of functional nuclear TDP-43 multimers due to disrupted N-terminal domain (NTD) interactions. To address this, we developed fluorescence lifetime (FLT)-based FRET biosensors to monitor TDP-43 multimerization in living cells that couple a full-length TDP-43 FLT-FRET biosensor screen with an NTD-deletion counter screen, forming the foundation of a novel high-throughput screening (HTS) platform. Screening the 2682 compound FDA-approved Selleck library, we identified the small molecule ketoconazole, which stabilizes functional nuclear TDP-43 multimers in an NTD-dependent manner with low micromolar potency. Ketoconazole rescues TDP-43 mislocalization and aggregation, restores SREBP2 mRNA levels under TDP-43 overexpression, improves neuronal health, and partially restores motor function in a TDP-43 C. elegans model. These findings establish both the biosensors and the HTS platform as innovative tools for TDP-43 drug discovery and support an exciting translational approach for targeting TDP-43 proteinopathies.}, } @article {pmid40493543, year = {2025}, author = {Lucassen, HJ and Prinsen, EC and Asseln, M and van Vliet, RO and Tuijthof, GJM}, title = {Assistive devices for ALS patients: exploring wishes and values through focus groups.}, journal = {Disability and rehabilitation. Assistive technology}, volume = {}, number = {}, pages = {1-13}, doi = {10.1080/17483107.2025.2516628}, pmid = {40493543}, issn = {1748-3115}, abstract = {PURPOSE: Amyotrophic Lateral Sclerosis (ALS) is a progressive disease leading to loss of muscle strength and control, and as such limiting patients' independence. Assistive devices can help individuals with ALS; however, their use by ALS patients is limited. To increase use rates, we expect that devices need to be tailored to ALS patients. The aim of this study was to identify wishes, requirements and values of ALS patients regarding assistive devices for the upper extremity through focus groups involving ALS patients, their relatives and medical professionals.

METHODS AND MATERIALS: Four focus groups were conducted, recorded and transcribed. Two focus groups with ALS patients and their relatives contained a "Day in a Life" and "Empathy map" method, while during two focus groups with medical professionals, "Day in the Life" method and "Provoking statements" were used. Activities mentioned were counted and categorized into "Daily activities" and "Elective activities".

RESULTS: Qualitative analysis of transcripts yielded three themes: (1) ALS patients' considerations on use and wishes for assistive devices, (2) external factors influencing the use of assistive devices and (3) change in ALS patients' needs over time. In addition to maintaining independence in activities of daily living, the results highlight that retaining the ability to perform elective activities such as hobbies, is important. Moreover, there is a clear need for assistive devices designed for ALS patients with limited upper extremity strength, but who are not confined to a wheelchair.

CONCLUSION: These findings can guide the development of assistive devices tailored to the needs of ALS patients.}, } @article {pmid40493233, year = {2025}, author = {Russo, T and Domi, T and Schito, P and Falzone, YM and Pozzi, L and Locatelli, M and Riva, N and Spinelli, EG and Agosta, F and Filippi, M and Quattrini, A}, title = {Osteopontin levels in the serum reflect anatomical disease progression in patients with amyotrophic lateral sclerosis.}, journal = {Journal of neurology}, volume = {272}, number = {7}, pages = {452}, pmid = {40493233}, issn = {1432-1459}, support = {Age-It: "Ageing Well in an Ageing Society"//Ministero dell'Università e della Ricerca/ ; RF-2021-12374238//Ministero della Salute/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/blood/pathology/diagnosis ; *Osteopontin/blood ; Male ; Female ; *Disease Progression ; Middle Aged ; Aged ; Retrospective Studies ; Biomarkers/blood ; Neurofilament Proteins/blood ; Adult ; Longitudinal Studies ; Severity of Illness Index ; Cohort Studies ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) lacks biomarkers for diagnosis, prognostic stratification, and evaluation of response to potential treatments. Previous research supported the role of serum osteopontin (OPN) levels as a potential biomarker in ALS. However, the associations of OPN serum levels with clinical features and their trend over the disease course have not been explored yet.

METHODS: We measured OPN serum levels in a retrospective cohort of 110 well-characterized patients with ALS, using a commercial ELISA kit, and analyzed their association with demographic and clinical features, as well as with other serum biomarkers. For a subset of patients, longitudinal measurements were available.

RESULTS: OPN serum levels differed significantly between patients with ALS and a cohort of 45 age and sex-matched healthy controls. However, when considering potential differential diagnoses, elevated OPN serum levels were not specific for ALS. Patients with an advanced disease stage (King's stage 3 or 4) exhibited significantly higher OPN serum levels compared to patients at earlier disease stages, whereas we did not observe any correlation with ALSFRS-R and progression rate. We observed an inverse correlation between OPN serum levels and BMI at diagnosis. Higher OPN serum levels predicted a shorter survival time and a shorter time to King's stage 4. No significant association between serum OPN and serum neurofilament light or glial fibrillary acid protein levels was observed. OPN serum levels were substantially stable over a 9-month observation time.

CONCLUSION: Our findings indicate that serum OPN is an informative biomarker in ALS, providing valuable prognostic insights, potentially reflecting the extent of disease, and demonstrating potential applications in clinical trials.}, } @article {pmid40493155, year = {2025}, author = {Kang, A and Qiao, Y and Pan, S and Yan, F and Chen, H and Bai, Y}, title = {From RIPK1 to Necroptosis: Pathogenic Mechanisms in Neurodegenerative Diseases.}, journal = {Neurochemical research}, volume = {50}, number = {3}, pages = {194}, pmid = {40493155}, issn = {1573-6903}, support = {24JRRA346//Natural Science Foundation of Gansu Province/ ; CY2023-QN-B03//"Cuiying Science and Technology Program" of the Second Hospital of Lanzhou University/ ; (23)0207//Foundation for International Medical Exchanges/ ; (23)1263//China Health Promotion Foundation/ ; }, mesh = {Humans ; *Necroptosis/physiology/drug effects ; *Receptor-Interacting Protein Serine-Threonine Kinases/metabolism ; *Neurodegenerative Diseases/metabolism/pathology/drug therapy ; Animals ; Signal Transduction/physiology ; }, abstract = {Receptor-interacting protein kinase 1 (RIPK1)-mediated necroptosis, a newly identified mode of regulated cell death, represents a significant pathogenic mechanism in multiple neurodegenerative disorders. Substantial experimental evidence indicates that RIPK1 regulates necroptotic cell death pathways in both neuronal and glial cell populations through activation of the canonical RIPK3-MLKL signaling cascade, thereby exacerbating neuroinflammatory responses and accelerating neurodegenerative progression. The pathological relevance of this molecular pathway has been extensively validated across multiple major neurodegenerative disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS). Pharmacological interventions targeting RIPK1 or its downstream effectors-particularly RIPK3 and MLKL-have demonstrated significant efficacy in mitigating disease-associated pathological manifestations. This highlights the RIPK1 signaling axis as a promising therapeutic target for neuroprotective strategies. Consequently, thorough investigation of RIPK1-mediated necroptosis in neurodegenerative settings holds considerable translational potential. Such inquiry deepens mechanistic understanding of disease pathogenesis while accelerating the advancement of innovative therapeutic approaches with direct clinical relevance.}, } @article {pmid40492096, year = {2025}, author = {Tzeplaeff, L and Galhoz, A and Meijs, C and Gomes, LC and Kovac, A and Menzel, A and Değirmenci, H and Alaamel, A and Kaya, HC and Çelik, AG and Dinçer, S and Korucuk, M and Karaüzüm, SB and Bayraktar, E and Çiftçi, V and Bilge, U and Koç, F and Demleitner, AF and Buchberger, A and von Heynitz, R and Gmeiner, V and Knellwolf, C and Mouzouri, M and Wuu, J and Başak, AN and Andersen, PM and Kohlmayer, F and Ashton, NJ and Kuban, W and Lenz, C and Rogers, ML and Zilka, N and Corcia, P and Lerner, Y and Weber, M and Koprusakova, MT and Uysal, H and Benatar, M and Menden, MP and Lingor, P}, title = {Identification of a presymptomatic and early disease signature for Amyotrophic Lateral Sclerosis (ALS): protocol of the premodiALS study.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, pmid = {40492096}, support = {R01 NS105479/NS/NINDS NIH HHS/United States ; }, abstract = {The median time to diagnosis of amyotrophic lateral sclerosis (ALS) is approximately 12 months after the onset of first symptoms. This diagnostic delay is primarily due to the nonspecific nature of early symptoms and the clinical challenges in differentiating ALS from its mimics. Therefore, the discovery of reliable biomarkers for the early and accurate diagnosis of ALS represents a critical medical need. A total of 330 participants will be recruited across six international study sites. The cohort will include (1) pre-symptomatic gene mutation carriers, (2) symptomatic individuals up to 12 months after symptom onset with either ALS, ALS mimics, or a pure motor syndrome with yet unclear assignment, and (3) healthy controls. Participants will engage in a one-year longitudinal study, consisting of an initial evaluation at baseline visit and a follow-up visit 12 months later. Assessments will include an environmental and medical history questionnaire, neurological examinations, olfactory testing, cognitive/behavioral evaluations, and the collection of biological samples (serum, plasma, urine, tear fluid, and cerebrospinal fluid). Proteomic, metabolomic, and lipidomic analyses will be performed using mass spectrometry and targeted immunoassays, with all samples processed under standardized protocols. The resulting multimodal dataset will be systematically integrated in an effort to uncover a clinico-molecular signature characteristic of presymptomatic and early ALS. These findings may have relevance to early ALS diagnosis and future clinical practice.}, } @article {pmid40492044, year = {2025}, author = {Roshni, J and Mahema, S and Janakiraman, V and Ahmad, SF and Al-Mazroua, HA and Ahmed, SSSJ}, title = {Effect of bovine milk-derived peptide on SNAP-25 of the neurotransmitter system in treating the sialorrhoea in chronic neurological diseases.}, journal = {Food science and biotechnology}, volume = {34}, number = {11}, pages = {2601-2610}, pmid = {40492044}, issn = {2092-6456}, abstract = {Sialorrhea is a prominent symptom of chronic neurological disorders like amyotrophic lateral sclerosis, Parkinson's disease, motor neuron disease, cerebral palsy, and stroke. Synaptosome-Associated Protein-25 (SNAP-25) plays a key role in triggering involuntary saliva secretion. This study aimed to identify SNAP-25-targeting bovine milk-derived peptides to mitigate sialorrhea, using computational and quantum atomistic simulation approach. Among 8559 bovine milk-derived peptides, 8499 were non-toxic, 7749 non-allergenic, 911 with blood-brain barrier crossing potential, and 175 with cell-penetrating capabilities. Using HAPPENN program, 20 non-hemolytic peptides were screened, while PeptideRanker predicted two physiologically active peptides. Protein-peptide docking followed by de novo structural modeling showed that CMPTFQFFK has a stronger inhibitory affinity (- 7.45 kcal/mol) for SNAP-25 than botulinum toxin. Additionally, dynamic simulations, free energy and quantum chemical studies confirmed the stability of CMPTFQFFK's with SNAP-25. Our study recommends CMPTFQFFK as a potential inhibitor of SNAP-25 for sialorrhea treatment, with further in vitro testing needed to confirm efficacy.}, } @article {pmid40492022, year = {2025}, author = {Ennis, R and Husted, C}, title = {Case Report: Treating Atrial Fibrillation with the Neubie Direct Current Electrical Stimulation.}, journal = {Medical devices (Auckland, N.Z.)}, volume = {18}, number = {}, pages = {291-295}, pmid = {40492022}, issn = {1179-1470}, abstract = {INTRODUCTION: A novel Neuro-Bio-Electric-Stimulation device (Neubie, Neufit, Austin, Texas, USA) using Direct Current (DC) has been used to treat various neurological conditions (ALS, MS, peripheral neuropathy, chronic pain) and functional limitations such as limited range of motion. One method, called the Master Reset Protocol, is thought to stimulate the vagus nerve system, impacting heart rate, digestion and other vital systems.

PURPOSE: We used the Master Reset Protocol on a subject experiencing paroxysmal Atrial Fibrillation (AFib) to assess whether this treatment might be effective in reversing a cardiac arrhythmia.

SUBJECT AND METHODS: A single subject is reported in this Case Report. The subject is a 62-year-old healthy, athletic male, 6'2″ tall, 165 lbs. with a good diet and is not obese nor has other exacerbating underlying conditions related to heart disease. The subject experiences arrhythmia approximately 1-2 times per month lasting generally 3 or more days per the subject. The Master Reset Method was initiated within 12 hours of arrhythmia onset, and arrhythmia before and after treatment was confirmed through subject observation and confirmed with pulse readings. A total of ten treatments were conducted over 7 months.

RESULTS: Reversal of arrhythmia was confirmed during or within 24 hours of treatment with DC application for all 10 treatments (100%). Two of the more severe cases of AFib required two treatments on the same day with confirmed reversal of AFib.

CONCLUSION: Treatment with Direct Current suggests a good correlation with reversal of arrhythmia. Further studies are planned to determine if similar, regular, treatments can be effective in preventing arrhythmia.}, } @article {pmid40491620, year = {2025}, author = {Sue, S and Yamazaki, S and Sue, K and Kinoshita, T and Yoshida, K}, title = {Combined Effects of Lung Volume Recruitment Training and Mechanical Insufflation-Exsufflation in a Patient With Advanced Amyotrophic Lateral Sclerosis Receiving Long-Term Mechanical Ventilation: A Case Report.}, journal = {Cureus}, volume = {17}, number = {5}, pages = {e83823}, pmid = {40491620}, issn = {2168-8184}, abstract = {Amyotrophic lateral sclerosis (ALS) degenerates both upper and lower motor neurons. Most patients with ALS require respiratory support due to deterioration of their respiratory muscles. Mechanical insufflation-exsufflation (MI-E) is one option that can help patients with weak cough strength to clear the airway, and it may potentially increase survival time. Another option is lung volume recruitment training (LVRT), a technique commonly used to maintain lung and chest wall flexibility. However, it requires specific equipment, such as one-way valves, to be applied to patients with ALS who undergo invasive mechanical ventilation with tracheostomy. Only limited studies have indicated the effectiveness of LVRT for patients with ALS. Moreover, no study is currently available on the effect of combining LVRT with MI-E. As the disease progresses, treatment options become increasingly limited, making it crucial to explore new therapeutic approaches for patients at the advanced stage. Here, we examined the effects of a combination of LVRT and MI-E in a 74-year-old female patient with ALS who had survived under invasive mechanical ventilation for nine years. We measured tidal volume (TV) and dynamic lung compliance (Cdyn) as respiratory parameters three months before and after the initiation of the combined therapy. Following the intervention, TV improved from 750.15 L/min (standard deviation (SD) ± 34.60) to 859.14 L/min (SD ± 75.63), and Cdyn increased from 24.18 cmH2O (SD ± 2.84) to 26.54 cmH2O (SD ± 2.92). These results suggest that MI-E combined with LVRT may improve lung compliance even in patients with ALS receiving long-term invasive mechanical ventilation.}, } @article {pmid40491248, year = {2025}, author = {Bernsen, S and Fabian, R and Koc, Y and Schumann, P and Körtvélyessy, P and Castro-Gomez, S and Meyer, T and Weydt, P}, title = {Serum Cardiac Troponin T Levels as a Therapy Response Marker in Tofersen-Treated ALS.}, journal = {Muscle & nerve}, volume = {72}, number = {3}, pages = {509-514}, pmid = {40491248}, issn = {1097-4598}, abstract = {INTRODUCTION/AIMS: Cardiac troponin T (cTnT) levels are elevated in the majority of persons with amyotrophic lateral sclerosis (ALS) and increase over time. Neurofilament light chain (NfL) is an established therapy response biomarker in ALS as superoxide dismutase1 (SOD1)-ALS patients treated with the antisense oligonucleotide tofersen show a decrease in NfL. In this study, we assess cTnT levels in SOD1-ALS at baseline and during tofersen treatment.

METHODS: cTnT was analyzed at baseline and during tofersen treatment in 23 SOD1-ALS patients at two specialized ALS centers in Germany and compared to a control cohort of 74 ALS patients without SOD1 variants.

RESULTS: cTnT levels increased in the control ALS cohort over time (p < 0.0001) but not in the tofersen group (p = 0.36). Creatine kinase (CK) and CK-MB levels did not show significant changes over time. The median monthly increase of cTnT was 0.045 points (IQR 0.02-0.08) in the control ALS cohort and 0.01 points (IQR -0.01-0.03) in the tofersen group (p = 0.0013). A significantly lower fold change in cTnT levels was observed in the tofersen-treated cohort (median 1.2; IQR 0.77-1.59) relative to the control group (median 1.89; IQR 1.35-2.75) (p = 0.0003). Nine (39%) patients treated with tofersen experienced a reduction in cTnT levels.

DISCUSSION: In this study, we describe a response signal of cTnT to tofersen treatment, which supports the value of cTnT as an independent biomarker in ALS. These results contribute to the notion that cTnT may provide additional value as a progression and treatment response biomarker in ALS complementary to NfL and warrant further investigation.}, } @article {pmid40490178, year = {2025}, author = {Akkum, FI and Ozbas, CE and Damar, M and Uversky, VN and Fayetorbay, R and Kang, DE and Woo, JA and Coskuner-Weber, O}, title = {Impacts of pathogenic mutations on the structures of the CHCHD10 monomer: An AlphaFold3 study linked to the generation of conformational ensembles.}, journal = {International journal of biological macromolecules}, volume = {318}, number = {Pt 2}, pages = {144970}, doi = {10.1016/j.ijbiomac.2025.144970}, pmid = {40490178}, issn = {1879-0003}, mesh = {Humans ; *Mitochondrial Proteins/genetics/chemistry ; *Mutation ; Models, Molecular ; Protein Conformation ; Protein Structure, Secondary ; }, abstract = {CHCHD10, a member of the coiled-coil-helix-coiled-coil-helix (CHCH) domain-containing protein family, plays a critical role in mitochondrial function. The link between pathological mutations and CHCHD10 is important and increasingly recognized, especially due to mitochondrial dysfunction and its association with neurodegenerative diseases. Several mutations in CHCHD10 have been directly linked to human diseases, such as Amyotrophic Lateral Sclerosis (ALS), Frontotemporal Dementia (FTD), mitochondrial myopathies, and Spinal Muscular Atrophy-Jokela type (SMAJ). In this study, we investigate the structural properties of wild-type and mutant CHCHD10 proteins using AlphaFold3 linked to the generation of conformational ensembles. Structural changes may modulate interactions, flexibility, and aggregation tendencies, potentially influencing neurodegenerative disease pathogenesis linked to mitochondrial dysfunction. Notably, disease-associated mutations like R15S, P23L, and S59L alter secondary structure formations such as 310-helices and β-sheets. Despite, we find that the compactness of CHCHD10 is not significantly altered by genetic mutations since radius of gyration values range between 32.69 Å and 35.94 Å. All in all, we find that the compactness is not but the secondary and tertiary structure properties are affected by pathological mutations. We propose that evolution may have optimized CHCHD10 to maintain a suitable radius of gyration that provides sufficient flexibility through its intrinsically disordered region while ensuring efficient interaction with diverse molecules. Thus, alterations in secondary and tertiary structures through mutations might be a mechanism for fine-tuning the protein's functionality while preserving its optimal state. These characteristics might be related to the pathologies of neurodegenerative diseases linked to mitochondrial dysfunction.}, } @article {pmid40489983, year = {2025}, author = {The Lancet Neurology, }, title = {Honouring the amyotrophic lateral sclerosis research pledge.}, journal = {The Lancet. Neurology}, volume = {24}, number = {7}, pages = {557}, doi = {10.1016/S1474-4422(25)00166-8}, pmid = {40489983}, issn = {1474-4465}, } @article {pmid40489798, year = {2025}, author = {Huang, J and Zhao, L and Xiang, P and Zhang, F and Yang, Y and Chao, L and Liu, W and Li, H and Zhang, X}, title = {Aminated Lignin/Cellulose-Based Hydrogel with High Adhesion for Wearable Sensors.}, journal = {Langmuir : the ACS journal of surfaces and colloids}, volume = {41}, number = {24}, pages = {15484-15493}, doi = {10.1021/acs.langmuir.5c01389}, pmid = {40489798}, issn = {1520-5827}, mesh = {*Hydrogels/chemistry ; *Lignin/chemistry/analogs & derivatives ; *Cellulose/chemistry ; *Wearable Electronic Devices ; Nanoparticles/chemistry ; Animals ; Swine ; }, abstract = {Hydrogels play a significant role in the flexibility, stretchability, and conductivity of wearable sensors. However, it is still a challenge to achieve multifunctional hydrogel sensors with excellent mechanical strength, outstanding self-adhesion, and high stimulus responsiveness for meeting various demands of practical applications. Here, this work presents a one-pot method to prepare a conductive hydrogel with multifunction by introducing aminated lignosulfonate (A-LS) and aminated cellulose nanocrystals (A-CNC) into the hydrogel matrix. Benefiting from the synergistic effect of dynamic reversible noncovalent bond network with the introduction of nanoparticles in the system, the resultant hydrogel showed excellent mechanical properties. In addition, the prepared hydrogels exhibited remarkable adhesion strength (pig skin: 24 kPa) with sustainable adhesion, which still maintained an adhesion strength above 18 kPa after 20 cycles of adhesion/separation. The resultant hydrogel sensor showed a wide operating range (0-200%), high sensitivity (GF = 0.71 at 0-100% strain; GF = 3.15 at 100-200% strain), and fast response time (320 ms). The high-value utilization of renewable forest biomass resources is conducive to the sustainable development of green chemistry.}, } @article {pmid40489721, year = {2025}, author = {Levison, L and Jepsen, P and Blicher, JU and Andersen, H}, title = {Hospital-Diagnosed Traumatic Head Injury and Associated Risk of Developing ALS: A Nationwide Population-Based Case-Control Study.}, journal = {Neurology}, volume = {105}, number = {1}, pages = {e213809}, doi = {10.1212/WNL.0000000000213809}, pmid = {40489721}, issn = {1526-632X}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/epidemiology/etiology/diagnosis ; Male ; Female ; Case-Control Studies ; Middle Aged ; Aged ; Risk Factors ; *Craniocerebral Trauma/epidemiology/complications/diagnosis ; Registries ; Adult ; Aged, 80 and over ; }, abstract = {BACKGROUND AND OBJECTIVES: Previous studies have suggested that traumatic head injury (THI) may be a risk factor of amyotrophic lateral sclerosis (ALS) development, yet the association remains unclear. We aimed to determine whether hospital-diagnosed THI is an important ALS risk factor, and we investigated the magnitude and duration of associated ALS risk.

METHODS: In this population-based case-control study, we used individual-level data linkage across nationwide health registers from 1980 to 2021 to identify patients with hospital-diagnosed ALS. Each patient was matched 1:10 with individuals from the general population by age, sex, and diagnostic index date. We used conditional logistic regression to examine the relative risk of ALS associated with having previous hospital-diagnosed THI. To avoid the effect of reverse causation, we investigated ALS risk within several time windows and repeated all analyses after restricting THI exposures to more than 3 years before the date of ALS diagnosis.

RESULTS: THI was observed in 4.7% of 5,943 ALS cases vs 3.7% of 59,426 controls, with a matched odds ratio (OR) of 1.3 (95% CI 1.1-1.4). However, the risk of ALS declined considerably with increasing time since head injury, with a high OR of 4.5 (95% CI 2.8-7.3) observed within the 6 months before ALS diagnosis. If head injury was suffered 6-12 months before ALS diagnosis, the OR was 2.4 (95% CI 1.4-4.0). Restricting the analysis to THI suffered more than 3 years before ALS diagnosis, we found no association with an OR of 1.1 (95% CI 1.0-1.3).

DISCUSSION: Although a strong association of ALS with THI experienced ≤1 year before ALS diagnosis was evident, our results suggest that this is due to reverse causation. When restricting the analysis to a period deemed relevant for causative events leading to ALS development, no association was observed. Consequently, we do not consider THI an important ALS risk factor. This study was limited by the inability to consider minor THIs not receiving hospital attendance. Future research should explore alternative models to unfold this possible ALS risk factor.}, } @article {pmid40489271, year = {2025}, author = {Li, B and Han, Y and Zhang, S and Wang, H and Zhao, Z and Zhai, Y}, title = {High-precision Edge Detection Guided by Flow Fields.}, journal = {IEEE transactions on image processing : a publication of the IEEE Signal Processing Society}, volume = {PP}, number = {}, pages = {}, doi = {10.1109/TIP.2025.3572763}, pmid = {40489271}, issn = {1941-0042}, abstract = {Edge detection is frequently employed to support downstream visual tasks. However, current edge detection methods still encounter two significant challenges: extracting complex textured targets and capturing valuable information from complex backgrounds. We propose FFED, a flow field-guided edge detection model. FFED integrates the three components of our design. FFED incorporates three designed components: the Feature Broadcast Module (FBM), the Antagonistic Bio-inspired Spatial Attention Module (ABSAM), a novel pixel difference convolution named ALS. The FBM serves as an implementation mode of the flow field, with its input pair selection strategy inspired by video processing.The FBM broadcasts high-level semantic features to high-resolution ones, preserving more meaningful texture details. Inspired by biological studies, we propose the ABSAM. ABSAM extracts valuable information from complex backgrounds by optimizing spatial modeling of data. The ALS exhibits enhanced capability in extracting gradient information and capturing subtle texture details that are easily overlooked. Experimental results demonstrate that FFED achieved competitive detection results on NYUD, BSDS500, and BIPED datasets, as well as good performance on industrial datasets. Additionally, the experiment verified the auxiliary effect of FFED on downstream visual tasks. The code is available at https://github.com/hanyuchen2022/Flow-field-guided-edge-detection-FFED-.}, } @article {pmid40489211, year = {2025}, author = {Gautam, P and Yadav, R and Vishwakarma, RK and Shekhar, S and Pathak, A and Singh, C}, title = {An Integrative Analysis of Metagenomic and Metabolomic Profiling Reveals Gut Microbiome Dysbiosis and Metabolic Alterations in ALS: Potential Biomarkers and Therapeutic Insights.}, journal = {ACS chemical neuroscience}, volume = {16}, number = {14}, pages = {2691-2706}, doi = {10.1021/acschemneuro.5c00254}, pmid = {40489211}, issn = {1948-7193}, mesh = {*Amyotrophic Lateral Sclerosis/metabolism/microbiology ; Humans ; *Gastrointestinal Microbiome/physiology ; *Dysbiosis/metabolism/microbiology ; Male ; *Metabolomics/methods ; Female ; Middle Aged ; Biomarkers/metabolism ; Aged ; Metagenomics/methods ; Feces/microbiology ; }, abstract = {ALS is a severe neurodegenerative disorder characterized by motor neuron degeneration, gut dysbiosis, immune dysregulation, and metabolic disturbances. In this study, shotgun metagenomics and [1]H nuclear magnetic resonance (NMR)-based metabolomics were employed to investigate the altered gut microbiome and metabolite profiles in individuals with ALS, household controls (HCs), and nonhousehold controls (NHCs). The principal component analysis (PCA) explained 33% of the variance, and the partial least-squares discriminant analysis (PLS-DA) model demonstrate R[2] and Q[2] values of 0.97 and 0.84, respectively, indicating an adequate model fit. The relative bacterial abundance was 99.34% in the ALS group and 98.94% in the HC group. Among the ten identified genera, Bifidobacterium, Lactobacillus, and Enterococcus were more prevalent in ALS individuals, while Lactiplantibacillus and Klebsiella were more abundant in the HC group. We identified 70 metabolites, including short-chain fatty acids (SCFAs), branched-chain amino acids (BCAAs), carbohydrates, and aromatic compounds, using NMR. Orthogonal partial least-squares discriminant analysis (O-PLS-DA) explained 15.8% of the variance, with a clear separation between the ALS and HC groups. Univariate receiver operating characteristic (ROC) analysis identified three fecal metabolites with AUC values above 0.70, including butyrate (0.798), propionate (0.727), and citrate (0.719). These metabolites may serve as potential biomarkers for ALS. The statistical model for metabolic pathway analysis revealed interconnected pathways, highlighting the complexity of metabolic dysregulation, as well as potential microbial and metabolic biomarkers in ALS. These results highlight the role of gut microbiome alterations in ALS and suggest potential avenues for therapeutic intervention.}, } @article {pmid40488810, year = {2025}, author = {Kulkarni, SR and Thokchom, B and Abbigeri, MB and Bhavi, SM and Singh, SR and Metri, N and Yarajarla, RB}, title = {The role of L-DOPA in neurological and neurodegenerative complications: a review.}, journal = {Molecular and cellular biochemistry}, volume = {}, number = {}, pages = {}, pmid = {40488810}, issn = {1573-4919}, abstract = {L-DOPA remains a cornerstone treatment for Parkinson's disease and is increasingly recognized for its role in various neurological and neurodegenerative disorders. As a direct precursor to dopamine, L-DOPA is synthesized from L-tyrosine through the action of tyrosine hydroxylase and is subsequently converted into dopamine via aromatic L-amino acid decarboxylase. Its ability to cross the blood-brain barrier (BBB) makes it a crucial therapeutic agent for restoring dopaminergic neurotransmission, thereby influencing motor function, cognition, and neuroprotection. Beyond Parkinson's, L-DOPA's therapeutic potential extends to neurodegenerative conditions such as Alzheimer's disease, Huntington's disease, multiple sclerosis, Lewy body dementia, and amyotrophic lateral sclerosis, where dopamine modulation plays a critical role. Furthermore, L-DOPA has demonstrated efficacy in neurological disorders including epilepsy, peripheral neuropathy, cerebrovascular diseases, and traumatic brain injury, suggesting broader neurobiological applications. However, long-term use is associated with challenges such as motor fluctuations, dyskinesias, and loss of therapeutic efficacy due to progressive neurodegeneration and alterations in dopaminergic pathways. Recent advancements in drug delivery systems, combination therapies, and nanotechnology, including plant-derived carbon dots, offer promising strategies to enhance L-DOPA's effectiveness while mitigating its limitations. This comprehensive review explores L-DOPA's synthesis, pharmacokinetics, mechanism of action, and its evolving role in neurological diseases, while highlighting ongoing challenges and future directions for optimizing its clinical application.}, } @article {pmid40488711, year = {2025}, author = {Tang, IW and Knekt, P and Rantakokko, P and Heliövaara, M and Rissanen, H and Ruokojärvi, P and Mukherjee, R and Weisskopf, MG}, title = {Pre-disease biomarkers of persistent organic pollutants (POPs) and amyotrophic lateral sclerosis (ALS) risk in Finland.}, journal = {Environmental health perspectives}, volume = {}, number = {}, pages = {}, doi = {10.1289/EHP16539}, pmid = {40488711}, issn = {1552-9924}, abstract = {BACKGROUND: Persistent organic pollutants (POPs) are toxic chemicals that bioaccumulate and were used in pesticides and industrial products/processes. POP-exposed occupations and environmental exposure to POPs have been associated with amyotrophic lateral sclerosis (ALS), but no study has evaluated the association with ALS when measuring POPs in samples collected before ALS onset.

OBJECTIVES: This study examined the relationship between pre-disease POP exposure and ALS risk.

METHODS: We conducted a nested case-control study pooling three Finnish cohorts (n=56,862). During a median follow-up of 27 years, 97 incident ALS cases were identified (mean age at ALS=68). Within each cohort, two controls per case were selected by individual matching for age, sex, municipality, and serum freeze-thaw cycles. Thirteen polychlorinated biphenyls (PCB) and nine organochlorine pesticides (OCP) were determined in serum samples collected at baseline and stored at -20C. We considered these POPs both in groups (similar congener, isomer, metabolite groups) and separately. Odds ratios and 95% confidence intervals were estimated using a conditional logistic model in a two-stage approach, further adjusting for smoking, occupation, marital status, BMI, and serum cholesterol level in primary models.

RESULTS: In the main model hexachlorobenzene (HCB) showed a positive association with ALS occurrence. In contrast, Σnon-dioxin-like (NDL) PCB and ΣDDT were significantly inversely associated with ALS incidence. Most other POP groups were non-significantly inversely associated with ALS risk. In co-pollutant models, the only notable changes were that Σdioxin-like PCB and ΣHCH showed large non-significant, elevated, ORs, suggesting some negative co-pollutant confounding. There were some suggestions of stronger findings when limiting to some subgroups.

DISCUSSION: We found little evidence that POPs were associated with ALS, but we identified a suggestive positive association with HCB and HCH. ΣNDL PCB and ΣDDT were inversely associated with ALS. This could suggest protective mechanisms or uncontrolled confounding by neuroprotective factors (e.g. fish oils). https://doi.org/10.1289/EHP16539.}, } @article {pmid40488544, year = {2025}, author = {Benzo-Iglesias, MJ and Rocamora-Pérez, P and Valverde-Martínez, MLÁ and García-Luengo, AV and Benzo-Iglesias, PM and López-Liria, R}, title = {Efficacy of respiratory muscle training in improving pulmonary function and survival in patients with amyotrophic lateral sclerosis: a systematic review and meta-analysis.}, journal = {Therapeutic advances in respiratory disease}, volume = {19}, number = {}, pages = {17534666251346095}, pmid = {40488544}, issn = {1753-4666}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology/mortality/therapy/diagnosis ; *Respiratory Muscles/physiopathology ; *Breathing Exercises/adverse effects/methods ; Randomized Controlled Trials as Topic ; Quality of Life ; Muscle Strength ; *Lung/physiopathology ; Treatment Outcome ; Recovery of Function ; Male ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that affects motor neurons, resulting in muscle weakness, loss of function, and ultimately death due to respiratory failure. Due to the lethal prognosis of ALS, respiratory muscle training has been proposed as a potentially beneficial intervention.

OBJECTIVES: To systematically review the efficacy of respiratory muscle training on lung function and respiratory muscle strength in ALS patients.

DESIGN: A systematic review and meta-analysis of randomized controlled trials.

DATA SOURCES AND METHODS: Articles published in PubMed, PEDro, Scopus, and Web of Science databases up to July 2024. The Preferred Reporting Items for Systematic reviews and Meta-Analyses 2020 statement guideline was followed. Included studies had (1) ALS patients, (2) respiratory muscle training, (3) physical exercise, usual care or no intervention were provided as a comparison group, (4) assessments of lung function, respiratory muscle strength, quality of life, survival, fatigue, and functional capacity outcome measures, and (5) a randomized controlled trial design. Methodological quality was analyzed using the PEDro scale, and risk of bias with the Cochrane Collaboration Risk of Bias Tool. Meta-analyses were performed with Review Manager software.

RESULTS: Five randomized controlled trials with 170 participants were included. The results showed that respiratory muscle training improved muscle strength, particularly maximum expiratory and inspiratory pressures. One study suggested inspiratory muscle training as a survival predictor in ALS patients. No significant effects were observed in forced vital capacity or quality of life. No adverse effects were reported.

CONCLUSION: Respiratory muscle training improves ventilatory function, particularly respiratory muscle strength, in people with ALS. While evidence is limited, it shows promise as an adjuvant therapy to enhance quality of life and survival. It has been registered in the PROSPERO (CRD42024568235).}, } @article {pmid40488385, year = {2025}, author = {Hermann, A and Prudlo, J and Kasper, E and Synofzik, M and Peters, O and Priller, J and Dinter, E and Wiltfang, J and Zerr, I and Flöel, A and Bürger, K and Höglinger, GU and Levin, J and Düzel, E and Teipel, S and Beichert, L and Brosseron, F and Wagner, M and Frommann, I and Ramirez, A and Yakupov, R and Schmid, M and Lingor, P and Haass, C and , and Spottke, A and Günther, R and Weydt, P and Neumann, M and Schneider, A}, title = {"The DESCRIBE-ALS-FTD study: a prospective multicenter observational study of the ALS-FTD spectrum".}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {}, number = {}, pages = {1-9}, doi = {10.1080/21678421.2025.2509617}, pmid = {40488385}, issn = {2167-9223}, abstract = {Background: Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) exhibit significant clinical, genetic and neuropathological abnormalities, and are regarded as belonging to a common disease spectrum, referred to as the ALS-FTD spectrum disorders. Our understanding of the underlying mechanisms of these diseases has advanced significantly, including molecular neuropathology, genetics and molecular pathophysiology. The heterogeneity of these diseases poses significant challenges to translational research and drug development, particularly in sporadic cases. Consequently, there is an urgent need to improve patient stratification for the successful execution of future clinical trials. Methods/Results: We here describe the study design of the DESCRIBE-ALS/FTD study which aims to address this research gap by undertaking a systematic sampling of patients from the ALS FTD spectrum, encompassing all possible disease variants. The main objective of the study is to systematically document detailed cross-sectional phenotyping and the temporal progression of motor and neuropsychological abnormalities that occur in both ALS and FTD. Additionally, it seeks to systematically correlate these abnormalities with genetics and potentially predictive biomarkers including longitudinal biomaterial sampling, brain imaging and brain banking. Furthermore, first-degree relatives of patients with disease-causing gene variants undergo the same assessments to also sample presymptomatic risk gene carriers. Conclusion: With this prospective registry study we aim to generate datasets which will help researchers identifying different disease traits in people with sporadic and genetic ALS and FTD and to develop biomarkers to identify preclinical and prodromal disease stages.}, } @article {pmid40488178, year = {2025}, author = {Benetton, C and Preuilh, A and Khamaysa, M and Chaumon, M and Lackmy-Vallée, A and Er, A and Pélégrini-Issac, M and Querin, G and Rouaux, C and Pradat, PF and Marchand-Pauvert, V}, title = {Encephalography cross-frequency coupling and brain alteration in amyotrophic lateral sclerosis.}, journal = {Brain communications}, volume = {7}, number = {3}, pages = {fcaf192}, pmid = {40488178}, issn = {2632-1297}, abstract = {The diagnosis of amyotrophic lateral sclerosis requires identifying degeneration in both brain and bulbospinal motor neurons. However, detecting cortical dysfunction remains challenging, as peripheral symptoms often overshadow upper motor neuron signs. Although transcranial magnetic stimulation and MRI are valuable tools, transcranial magnetic stimulation is challenged as disease progresses but also at early stage in some patients, and brain MRI shows in most cohorts no significant change at the time of diagnosis. This emphasizes the need for neuromarkers facilitating detection of cortical dysfunction and longitudinal monitoring. EEG offers promising avenues. Accordingly, we recently identified altered theta-gamma phase-amplitude coupling in amyotrophic lateral sclerosis. The present study aimed to further explore phase-amplitude coupling in patients, focusing not only on theta and gamma bands but also on alpha and beta bands, and the link with handedness and brain structure. Resting-state EEG was recorded in 26 patients with amyotrophic lateral sclerosis and 26 age- and sex-matched controls, alongside anatomical and diffusion MRI. PAC was calculated between slow and gamma oscillations at five sensorimotor electrodes bilaterally. Grey and white matter integrity was evaluated through cortical thickness measurements and diffusion metrics along the corticospinal tract. Results revealed significantly decreased theta-gamma PAC in the dominant hemisphere of patients, without changes in band powers or other frequency couplings. MRI confirmed well-known handedness-related brain structural asymmetry in both groups, although it was less pronounced in patients. Specifically, diffusion metrics were altered in the most caudal segment (brainstem level) of the pyramidal tract within the dominant hemisphere in patients. These findings align with lateralized theta-gamma PAC alterations and the greater vulnerability of the dominant hemisphere to amyotrophic lateral sclerosis. No correlation was found between electrophysiological and diffusion metrics, likely because they are related to different mechanisms: PAC alteration being presumably linked to excitation/inhibition imbalance preceding upper motor neuron degeneration. Moreover, theta-gamma PAC was found to be particularly altered in patients with altered cognitive scores, consistent with previous findings in patients with mild cognitive impairment. Lastly, receiver operating characteristic analyses demonstrated that PAC outperformed diffusion MRI in diagnostic accuracy, underscoring its potential as a very sensitive marker of cortical dysfunction in amyotrophic lateral sclerosis. Although these results need validation in a larger cohort at different stages of the disease and across different forms (sporadic and familial), they confirm that PAC can detect cortical dysfunctions in amyotrophic lateral sclerosis.}, } @article {pmid40487949, year = {2025}, author = {Kumar, S}, title = {Nomogram-based strategy to predict relapse-free survival in patients with gastrointestinal stromal tumor using inflammatory indicators.}, journal = {World journal of gastrointestinal oncology}, volume = {17}, number = {5}, pages = {103127}, pmid = {40487949}, issn = {1948-5204}, abstract = {Zhao et al's investigation on the assessment of inflammatory markers prognostic value for relapse-free survival in patients with gastrointestinal stromal tumor (GIST) using a nomogram-based approach is a scientific approach. This study explored the potential of an inflammatory marker-based nomograph model, highlighting the relapse-free survival-associated risk factors prognostic potential in patients with GIST. The author assessed 124 samples from patients with GIST to find an association between inflammatory markers and tumor size in a retrospective study using multivariate regression analysis. Further, a nomogram model was developed to identify the independent risk factors for the prognosis. GIST clinical treatment can use preoperative monocyte/lymphocyte ratio and platelet/lymphocyte ratio for relapse-free survival prognosis as independent factors.}, } @article {pmid40486953, year = {2025}, author = {Lehrer, S and Rheinstein, PH}, title = {Insulin and Metformin are Associated With Reduced Risk of Amyotrophic Lateral Sclerosis.}, journal = {Chronic diseases and translational medicine}, volume = {11}, number = {2}, pages = {148-155}, pmid = {40486953}, issn = {2589-0514}, abstract = {BACKGROUND: Type 2 diabetes (T2D), but not type 1, protected against amyotrophic lateral sclerosis (ALS). In T2D serum insulin is normal or elevated in the early stages. Type 1 diabetes, characterized by a total lack of insulin, is associated with an increased risk of ALS. The antidiabetic metformin also protects against ALS. Connexin 43 (Cx43), an astrocyte protein, operates as an open channel via which toxic substances from astrocytes reach motor neurons to cause ALS.

METHODS: In the current study we analyzed FDA MedWatch data to determine whether insulin or metformin could reduce the risk of ALS. We performed in silico molecular docking studies and molecular dynamics simulation with Cx43 to determine if insulin or metformin dock within the Cx43 channel and can block it effectively, again reducing risk of ALS.

RESULTS: In MedWatch, Insulin use is associated with a significantly reduced risk of ALS (Proportional Reporting Ratio 0.401). Metformin use is associated with a significantly reduced risk of ALS (PRR 0.567). The Human insulin heterodimer docked within center of the Cx43 channel, effectively blocking it. Molecular dynamics simulation showed that the block is highly stable and may be responsible for the protective effect of T2D on ALS. Metformin docks within the Cx43 channel, but the relatively small size of the metformin molecule may not allow it to obstruct the passage of toxic substances from astrocytes to motor neurons.

CONCLUSION: MedWatch data indicate that both insulin and metformin reduce risk of ALS. The results of our in silico docking study and molecular dynamics simulation corroborate our previous findings with Cx31. Insulin docks within the open hemichannel of hexameric Cx43, potentially blocking it. Molecular dynamics simulation showed that the block is stable and may be responsible for the protective effect of T2D and insulin on ALS.}, } @article {pmid40485888, year = {2025}, author = {Liu, Y and Ren, Y and Song, P}, title = {Traditional Chinese medicine for intractable and rare diseases: Research progress and future strategies.}, journal = {Intractable & rare diseases research}, volume = {14}, number = {2}, pages = {109-121}, pmid = {40485888}, issn = {2186-3644}, abstract = {Rare diseases have become a global public health challenge due to their low prevalence, difficult diagnosis, and limited treatment options. Intractable diseases are more common but often involve complex mechanisms, treatment with limited efficacy, and high medical costs, placing a heavy burden on patients and healthcare systems. In recent years, traditional Chinese medicine (TCM) has demonstrated unique advantages in the treatment of intractable and rare diseases and has gradually become an important complementary treatment. The current work is a systematic review of the progress of clinical and experimental research on TCM in typical rare diseases such as amyotrophic lateral sclerosis (ALS), systemic lupus erythematosus (SLE), mitochondrial encephalomyopathy, aplastic anemia (AA), and Wilson's disease (WD). It focuses on the multi-target therapeutic mechanisms of key Chinese herbal compound formulas, including immune regulation, antioxidative stress, and neuroprotection. The core TCM theories of "syndrome differentiation", "different treatments for the same disease" and the "same treatment for different diseases" are also discussed in the context of personalized medicine. In recent years, China has continuously promoted the development of TCM through a series of national plans and supportive policies, such as the 14th Five-Year Plan for TCM development, funding for key special projects, expedited approval pathways, and expanded coverage by medical insurance. These efforts have provided strong support for the clinical translation of TCM and technological innovation in the field of intractable and rare diseases. Notwithstanding the encouraging advances, the field of Chinese medicine continues to grapple with numerous challenges. In the future, the enhancement of mechanistic studies and quality multicenter clinical trials needs to be promoted while further enhancing policy support and international collaboration to substantiate the scientific basis and clinical value of TCM in the prevention and treatment of intractable and rare diseases.}, } @article {pmid40485533, year = {2025}, author = {Alves, I and Gromicho, M and Pronto-Laborinho, AC and Lopes, D and Oliveira Santos, M and De Carvalho, M}, title = {Federated sport activity in amyotrophic lateral sclerosis: a case-control study.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {}, number = {}, pages = {1-8}, doi = {10.1080/21678421.2025.2511124}, pmid = {40485533}, issn = {2167-9223}, abstract = {Amyotrophic lateral sclerosis (ALS) develops in a multistep process combining environmental variables and genes. Among the identified risk factors, the role of regular vigorous physical activity is still debatable. Objective: This case-control study investigated the relationship between ALS and different degrees of sports engagement, with federated status as a proxy for strenuous activity. Methods: 586 ALS patients and 558 controls were consecutively assessed by using a standard questionnaire. Due to low female participation in regular or intensive sports activity, the study focused on men (327 with ALS and 314 controls). Results: Overall, football (soccer) had the most practitioners (n = 137, 35.8%), accounting for 62.1% of ALS and 32.3% of control federated athletes. Male football players have a 3.07-fold increased ALS risk (95% CI: 1.82-5.19) compared to other men (p < 0.0001) and 3.43-fold increase (95% CI: 1.77-6.68) compared to those federated in other sports (p = 0.0003). After controlling for age and trauma, football players still had 2.91-fold (95% CI: 1.70-5.01) increased risk compared to non-federated and non-participants in contact sports intensively. No significant ALS risk difference existed for other sports practiced with identical intensity and contact levels. Clinical characteristics of ALS federated football players were similar to other ALS patients. Conclusion: Our results suggest ALS susceptibility is not linked to general physical activity, but specifically to competitive football, regardless of a history of head and neck trauma. Given football's popularity, even a small risk increase could impact many. Further research is required to understand the mechanisms linking football to ALS, and why this association is not observed in other sports.}, } @article {pmid40485494, year = {2025}, author = {Genge, A and Pattee, GL and Sobue, G and Aoki, M and Yoshino, H and Couratier, P and Lunetta, C and Petri, S and Selness, D and Todorovic, V and Sasson, N and Hirai, M and Takahashi, F and Salah, A and Apple, S and Wamil, A and Kalin, A and Jackson, CE}, title = {Safety Extension Study of Edaravone Oral Suspension in Patients With Amyotrophic Lateral Sclerosis for up to an Additional 96 Weeks of Treatment.}, journal = {Muscle & nerve}, volume = {72}, number = {3}, pages = {450-454}, pmid = {40485494}, issn = {1097-4598}, support = {//Mitsubishi Tanabe Pharma America Inc/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy ; *Edaravone/administration & dosage/adverse effects/therapeutic use ; Male ; Female ; Middle Aged ; Aged ; Administration, Oral ; *Free Radical Scavengers/administration & dosage/adverse effects/therapeutic use ; Adult ; Suspensions ; Treatment Outcome ; }, abstract = {INTRODUCTION/AIMS: Edaravone intravenous (IV) and oral suspension have been shown to have similar pharmacokinetics, safety, and slowing of functional decline in patients with amyotrophic lateral sclerosis (ALS). Study MT-1186-A01 indicated that edaravone oral suspension was well-tolerated over 48 weeks, with no new safety concerns identified relative to existing safety data of IV edaravone, including Study MCI186-19. The aim of this study was to assess the long-term safety and tolerability of edaravone oral suspension in patients with ALS.

METHODS: Study MT-1186-A03 (NCT04577404) was a phase 3, open-label, multi-center, extension study that evaluated the long-term safety of edaravone oral suspension over an additional 96 weeks in patients with ALS who have completed the initial 48 weeks of Study MT-1186-A01, for a total of up to 144 weeks of treatment. Patients received a 105-mg dose of edaravone administered in treatment cycles identical to the approved edaravone on/off dosing schedule. Patients had definite, probable, probable-laboratory-supported, or possible ALS.

RESULTS: In Study MT-1186-A03, edaravone oral suspension was well tolerated with no new safety concerns. The most common treatment-emergent adverse events (TEAEs) were fall, muscular weakness, dyspnea, constipation, and dysphagia. These TEAEs were consistent with the safety profile for edaravone from previous clinical trials.

DISCUSSION: These results help establish the long-term safety and tolerability profile of edaravone oral suspension.}, } @article {pmid40484835, year = {2025}, author = {Zhao, JR and Pang, XY and Bai, JM and Zhang, JH and Wang, HF and Li, M and Chen, ZH and Cheng, HM and Ling, L and Huang, XS}, title = {[Progression patterns of lower motor neuron involvement in the lower medulla oblongata and cervical spinal cord of amyotrophic lateral sclerosis patients].}, journal = {Zhonghua yi xue za zhi}, volume = {105}, number = {21}, pages = {1721-1727}, doi = {10.3760/cma.j.cn112137-20241229-02957}, pmid = {40484835}, issn = {0376-2491}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology/pathology ; *Medulla Oblongata/pathology ; Male ; Female ; *Cervical Cord/pathology ; Electromyography ; *Motor Neurons/pathology ; Middle Aged ; Disease Progression ; Adult ; Aged ; *Spinal Cord/pathology ; }, abstract = {Objective: To investigate the lower motor neuron (LMN) involvement patterns in the lower medulla oblongata and cervical spinal cord in amyotrophic lateral sclerosis (ALS) patients. Methods: The needle electromyography (EMG) data of 200 patients with non-thoracic onset sporadic ALS, hospitalized in the Neurology Department of the First Medical Center of the Chinese PLA General Hospital from September 2022 to December 2023, were retropectively analyzed. All participants met the EI Escorial-Revised diagnostic criteria. According to the onset site, the patients were divided into the lower medulla oblongata onset group(34 cases), the spinal cord onset group(166 cases) [including the lower cervical spinal cord onset group (92 cases) and the lumbosacral spinal cord onset group (74 cases)]. Electromyography (EMG) abnormalities in the muscles innervated by the lower medulla oblongata and cervical cord were counted, and the characteristics of LMN involvement were analyzed. The binomial distribution test was used to determine whether the progression of LMN involvement to the second central nervous system segment was random. Results: Among 200 ALS patients, there were 111 males (55.5%) and 89 females (44.5%), with an age onset of 28-86 (56±11) years. 20 (10.0%) cases with normal sternocleidomastoid (SCM)-EMG or trapezius (TRA)-EMG results, and 7 (3.5%) cases with normal SCM-EMG and TRA-EMG results were observed in patients with LMN involvement in both the lower medulla oblongata and lower cervical spinal cord. The abnormal rates of EMG at the onset of lower cervical spinal cord were tongue muscle (GEN)-EMG (88.2%, 30/34), TRA-EMG (70.6%, 24/34) and SCM-EMG (67.6%, 23/34), respectively. The abnormal rates of EMG at the onset of lower cervical spinal cord were TRA-EMG (72.8%, 67/92), SCM-EMG (38.0%, 35/92) and GEN-EMG (32.6%, 30/92), respectively. The binomial distribution test showed that the progression of LMN involvement to the second segment of the central nervous system was not random (all P<0.05). In low bulbar onset patients, the abnormal rate of LMN involvement was higher in the lower cervical spinal cord segment [100.0% (34/34)], and lower in the lumbosacral spinal cord segment[91.2% (31/34)]. In the lower cervical spinal cord onset group, the abnormal rate of LMN involvement was lower in the the low medulla obliterum[32.6% (30/92)] and high in the lumbosacral spinal cord [96.7% (89/92)].In the lumbosacral spinal cord onset group, the abnormal rate of LMN involvement was low in the low medulla oblata [27.0% (20/74)] and high in the lower cervical spinal cord [94.6% (70/74)]. Conclusions: The progression of LMN involvement in the lower medulla oblongata and cervical spinal cord is primarily continuous, while a discontinuous progression pattern was also observed. The lower medulla oblongata of ALS patients with spinal onset is relatively less involved in disease progression.}, } @article {pmid40482989, year = {2025}, author = {Qin, J and He, Y and Yu, W and Zhang, Z and Chen, X and Hu, Y and Jiang, H}, title = {Knockdown of OPTN modulates miRNA-125b-5p expression via NF-κB pathways in amyotrophic lateral sclerosis.}, journal = {Archives of biochemistry and biophysics}, volume = {771}, number = {}, pages = {110499}, doi = {10.1016/j.abb.2025.110499}, pmid = {40482989}, issn = {1096-0384}, mesh = {*Amyotrophic Lateral Sclerosis/metabolism/genetics/pathology ; Animals ; *MicroRNAs/genetics/metabolism ; Mice ; Membrane Transport Proteins ; Cell Cycle Proteins ; Microglia/metabolism/pathology ; Exosomes/metabolism ; *NF-kappa B/metabolism ; Signal Transduction ; *Transcription Factor TFIIIA/genetics/metabolism ; Apoptosis ; Cell Line ; Gene Knockdown Techniques ; Gene Expression Regulation ; Humans ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive fatal neurodegenerative disease characterized by severe dysfunction in upper and lower motor neurons. Previous studies have reported that the optineurin gene (OPTN) downregulation is one of the causative genetic factors for ALS, leading to the dysfunction of optineurin (OPTN), a multifunctional protein implicated in several cellular processes. Herein, we found that conditional knockout of the Optn gene in mouse microglia leads to activation of microglia. In subsequent studies, we also found that OPTN knockdown in BV2 cells leads to the activation of BV2 cells and promotes the apoptosis of co-cultured NSC34 cells via exosomes derived from BV2 cells in vitro. In contrast, OPTN knockdown in NSC34 cells did not cause apoptosis of the NSC34 cells themselves. It was suggested that microglia activation is involved in ALS initiation and development, but the nature of microglial-neuronal interactions remained elusive, requiring further exploration. Exosomes have been proven to be essential mediators. Notably, increased miRNA-125b-5p expression was uncovered in BV2 cells with the OPTN gene silenced, their derived exosomes, as well as the cocultured NSC34 cells. Interestingly, we proved that increased miRNA-125b-5p enhanced the apoptosis of NSC34 cells. We further noted that the overexpression of miRNA-125b-5p in BV2 cells can be regulated by an NF-κB activator (LPS) or inhibitor (withaferin A). Altogether, this study showed that silencing the OPTN gene may overexpress miRNA-125b-5p levels via the classical NF-κB pathway in BV2 cells. Up-regulated miRNA-125b-5p might be transmitted from exosomes to NSC34 cells, resulting in NSC34 cells apoptosis. Microglial-neuronal interactions mediated by exosomes were the crucial mechanism of OPTN gene downregulation leading to ALS, and this conclusion had been verified in cell models.}, } @article {pmid40482900, year = {2025}, author = {La Cognata, V and Guarnaccia, M and Morello, G and Gentile, G and Cavallaro, S}, title = {Predicting amyotrophic lateral sclerosis in the pre-symptomatic phase: Insights from SOD1G93A mouse gene expression profiles.}, journal = {Experimental neurology}, volume = {392}, number = {}, pages = {115329}, doi = {10.1016/j.expneurol.2025.115329}, pmid = {40482900}, issn = {1090-2430}, mesh = {Animals ; *Amyotrophic Lateral Sclerosis/genetics/diagnosis/metabolism ; Mice, Transgenic ; Mice ; *Superoxide Dismutase-1/genetics ; Gene Expression Profiling/methods ; *Transcriptome/genetics ; Disease Models, Animal ; Spinal Cord/metabolism ; Superoxide Dismutase/genetics ; Humans ; Disease Progression ; Male ; Motor Neurons/metabolism ; Female ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fast-paced fatal disease that requires immediate intervention to slow down the course of pathology and improve patients' quality of life. However, in most cases, ALS is diagnosed too late. For this reason, an accurate diagnostic test is urgently needed to identify ALS patients early, enabling a timely introduction of novel therapeutics and effective monitoring of disease progression. To address this significant unmet medical need, we explored a transcriptome-based signature to predict ALS during the preclinical phase. Using publicly available gene expression profiles from central nervous system (lumbar isolated motor neurons and spinal cord homogenates) of transgenic SOD1G93A mice with different genetic background and their respective control littermates, covering pre-symptomatic to late stages of the disease, we identified 463 differentially expressed genes (DEGs), primarily involved in immune response and metabolic processes. Based on this ALS gene-associated signature, we tested three machine learning binary classifiers (Support Vector Machine, Neural Network and Linear Discriminant Analysis), which demonstrated highly significant predictive power in discriminating mutant SOD1G93A from controls mice, even at pre-symptomatic stages. This was evident in both the discovery cohort and in two additional peripheral cross-tissue validation datasets from preclinical SOD1G93A sciatic nerve and muscles. Our study provides the first proof of concept for early ALS detection using a machine learning-based transcriptomic classifier. This could lead to earlier diagnosis, potentially enabling effective monitoring of disease progression and earlier interventions.}, } @article {pmid40482733, year = {2025}, author = {Ting, CH and Tai, ST and Chang, HY and Huang, PY and Cheng, LF and Lai, HJ and Kuo, YC and Kao, CH and Wang, IF and Tsai, LK}, title = {Baicalein benefits amyotrophic lateral sclerosis via reduction of Intraneuronal misfolded protein.}, journal = {Biochimica et biophysica acta. General subjects}, volume = {1869}, number = {8}, pages = {130831}, doi = {10.1016/j.bbagen.2025.130831}, pmid = {40482733}, issn = {1872-8006}, mesh = {*Flavanones/pharmacology/therapeutic use ; *Amyotrophic Lateral Sclerosis/drug therapy/metabolism/pathology ; Animals ; *Superoxide Dismutase-1/metabolism/genetics ; Mice ; Protein Folding/drug effects ; *Motor Neurons/drug effects/metabolism/pathology ; Humans ; Mice, Transgenic ; Disease Models, Animal ; *Neuroprotective Agents/pharmacology ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative disease characterized by muscle weakness and atrophy, with limited treatment options. The accumulation of misfolded proteins, such as misfolded superoxide dismutase 1 (mSOD1), contributes significantly to neuronal degeneration in ALS. Therapies targeting misfolded proteins represent a promising strategy. Baicalein, a flavonoid compound with neuroprotective properties, has shown efficacy in clearing misfolded proteins and improving behaviors in rodent models of Alzheimer's and Parkinson's diseases. However, its effects in ALS remain largely unexplored. This study demonstrated that baicalein treatment reduced total and misfolded SOD1 protein levels in both soluble and insoluble fractions of a motor neuron cell line overexpressing mutant SOD1. Baicalein also reduced intracellular SOD1 aggregates in cultured motor neurons transfected with SOD1/G93A, preserving neurite length. In an ALS mouse model expressing the SOD1/G93A transgene, baicalein treatment decreased mSOD1 aggregation, increased spinal motor neuron density, and reduced neuromuscular junction denervation. Furthermore, baicalein partially improved motor behaviors, as assessed by the rotarod test. These findings highlight baicalein's potential as a therapeutic agent for ALS, targeting intraneuronal misfolded proteins to ameliorate pathological changes and preserve motor function.}, } @article {pmid40482730, year = {2025}, author = {Mori, H and Sato, T and Tsuboguchi, S and Takahashi, M and Nakamura, Y and Hoshina, K and Kato, T and Fujii, M and Onodera, O and Ueno, M}, title = {TDP-43 mutants with different aggregation properties exhibit distinct toxicity, axonal transport, and secretion for disease progression in a mouse ALS/FTLD model.}, journal = {Neurobiology of disease}, volume = {212}, number = {}, pages = {106988}, doi = {10.1016/j.nbd.2025.106988}, pmid = {40482730}, issn = {1095-953X}, mesh = {Animals ; *Amyotrophic Lateral Sclerosis/pathology/genetics/metabolism ; *DNA-Binding Proteins/genetics/metabolism/toxicity ; Disease Progression ; Mice ; Disease Models, Animal ; *Axonal Transport/physiology ; Mutation/genetics ; *Frontotemporal Lobar Degeneration/pathology/metabolism/genetics ; Mice, Transgenic ; Neurons/metabolism/pathology ; Cells, Cultured ; Protein Aggregation, Pathological/metabolism/genetics/pathology ; Humans ; Mice, Inbred C57BL ; }, abstract = {TDP-43 accumulates and forms inclusions in neurons in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) and is assumed to cause neurodegenerative processes. The morphologies and cellular and areal distributions of accumulated TDP-43 inclusions are pathologically diverse among ALS/FTLD patients; however, whether and how different types of TDP-43 affect the process and severity of disease progression are not fully understood. Here, we compared the pathological events evoked by TDP-43 mutations, which have different aggregation properties, in cultured neurons and the cerebral cortex in mice. We selected TDP-43[C173/175S] and TDP-43[G298S] as aggregation-prone and nonprone mutants, respectively. Cytoplasmically expressed TDP-43[C173/175S] induced insoluble inclusions more robustly than TDP-43[G298S] did. In contrast, TDP-43[G298S] induced cell death more severely than TDP-43[C173/175S]. TDP-43[G298S] was further found to be efficiently transported in axons and led to axon degeneration, while this effect was not obvious in TDP-43[C173/175S]. Instead, TDP-43[C173/175S] was frequently trapped in the axon initial segments. Finally, TDP-43[G298S] was secreted in exosomes and transferred to oligodendrocyte-lineage cells in vitro more efficiently than TDP-43[C173/175S] to induce cell death. The transfer further evoked cytokine responses in microglial cells. These data revealed that different aggregation properties of TDP-43 cause distinct pathological events. These findings may explain the differences in the neurodegenerative progression and distribution observed among patients with ALS and FTLD.}, } @article {pmid40482593, year = {2025}, author = {Tankisi, H and Jacobsen, AB and Fanella, G and Cengiz, B and Kılınç, H and Matamala, JM and Moreno-Roco, J and Abrahao, A and Zinman, L and Koltzenburg, M and Howells, J and Samusyte, G and Awiszus, F and Bostock, H}, title = {Short-interval intracortical inhibition and facilitation in amyotrophic lateral sclerosis related to disease phenotype.}, journal = {Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology}, volume = {176}, number = {}, pages = {2110770}, doi = {10.1016/j.clinph.2025.2110770}, pmid = {40482593}, issn = {1872-8952}, abstract = {OBJECTIVE: To investigate the relationship between short-interval intracortical inhibition (SICI), short-interval intracortical facilitation (SICF) and amyotrophic lateral sclerosis (ALS) phenotype, using threshold-tracking transcranial magnetic stimulation (TMS).

METHODS: A new paired-pulse TMS protocol was applied to 49 patients with ALS and 49 age-matched healthy controls. Motor evoked potentials (MEPs) were recorded from first dorsal interosseus muscle, while paired pulses were delivered at interstimulus intervals (ISI) of 1.0, 2.5 or 3.0 ms, with stimuli related to the resting motor threshold for a 200 µV MEP. For each ISI, 6 SICI and 3 SICF pulse pairs with different conditioning stimuli were randomised and interleaved with test-alone stimuli.

RESULTS: ALS phenotypes were characterised as Pyramidal (n = 12, with prominent upper motor neuron signs), Classic (n = 20, with limb onset), or Bulbar (n = 17). Compared with healthy controls, Bulbar patients had significantly less inhibition at all ISIs, while SICI in Pyramidal patients was normal, and in Classic patients intermediate. The only SICF abnormalities independent of the changes in SICI were less facilitation in Pyramidal patients at ISIs 1 and 3 ms.

CONCLUSION: Changes in SICI and SICF depend on ALS phenotype.

SIGNIFICANCE: ALS phenotypes should be matched between treatment and placebo arms of clinical trials.}, } @article {pmid40482451, year = {2025}, author = {Attiq, A and Afzal, S and Raman, H and Ahmad, W}, title = {Neuroinflammation to neurodegeneration: Boulevard of broken nerves.}, journal = {International immunopharmacology}, volume = {161}, number = {}, pages = {115015}, doi = {10.1016/j.intimp.2025.115015}, pmid = {40482451}, issn = {1878-1705}, mesh = {Humans ; Animals ; *Neuroinflammatory Diseases/immunology/drug therapy/therapy ; *Neurodegenerative Diseases/immunology/drug therapy/therapy ; *Anti-Inflammatory Agents/therapeutic use ; Cytokines/metabolism ; }, abstract = {Neuroinflammation is caused by various factors, such as the activation of glial cells, the excessive release of chemokines and cytokines, and the accumulation of blood cells in the brain parenchyma. The inflammatory processes occur in acute and chronic phases, with traumatic brain injuries triggering the release of neurotoxins from CNS-specific glial cells. Furthermore, activation of microglia, astrocytes, and mast cells worsens the situation by producing pro-inflammatory cytokines, chemokines and glia maturation factors. Chronic activation of astroglia and microglial cells promotes loss of neurons, memory, and impaired learning capacity, leading to neurodegenerative disorders such as Parkinson's disease, Alzheimer's disease, Huntington's disease, and amyotrophic lateral sclerosis. These implications have led to a rational search for inflammatory druggable targets. Based on various preclinical and clinical studies, NSAIDs (aspirin, ibuprofen, diclofenac, and mefenamic acid), SSRIs (fluoxetine and sertraline), antipsychotics (risperidone), corticosteroids (dexamethasone), antidiabetics (metformin and rosiglitazone), and statins (simvastatin and atorvastatin) have exhibited promising results. These drugs have anti-inflammatory and neuromodulation activities that enhance neuroplasticity and effectively manage neurodegenerative symptoms. In addition, non-pharmacological interventions such as art creation and physical exercise have been linked with improving neural development and stimulating the production of anti-inflammatory cytokines, which can attenuate disease progression and promote synaptic plasticity. Hence, it is imperative to understand the complex interplay between glial cells, inflammatory signalling and neural pathways. We reviewed the interconnected pathways between neuroinflammation and neurodegeneration. Moreover, recommendations for pharmacological and non-pharmacological interventions to address these issues are discussed herein.}, } @article {pmid40481583, year = {2025}, author = {Johnson, B and Gibson, G and Baskerville, D and Castellano, G and de Courcy, J and Iqbal, H and Piercy, J and Williams, A and Pinedo-Villanueva, R and Rylands, A}, title = {Health-related quality of life and productivity burden for non-professional caregivers of adults with rare diseases: a real-world study.}, journal = {Orphanet journal of rare diseases}, volume = {20}, number = {1}, pages = {282}, pmid = {40481583}, issn = {1750-1172}, mesh = {Humans ; *Quality of Life ; *Caregivers/psychology ; Male ; Female ; Middle Aged ; *Rare Diseases ; Adult ; Efficiency ; Aged ; Surveys and Questionnaires ; Cost of Illness ; }, abstract = {BACKGROUND: Rare diseases present a substantial patient burden, but the impact on non-professional caregivers is poorly understood. We explored the health-related quality of life (HRQoL) and productivity burden on caregivers of adults with rare diseases.

METHODS: We analysed physician- and caregiver-reported real-world data from France, Germany, Italy, Spain, the United Kingdom, and the United States of America collected July 2017-March 2021 via Adelphi Disease Specific Programmes™ in amyotrophic lateral sclerosis (ALS), eosinophilic esophagitis (EoE), graft versus host disease (GvHD), Huntington's disease (HD), myasthenia gravis (MG), and progressive supranuclear palsy (PSP). Non-professional caregivers completed the EQ-5D-5L and Work Productivity and Activity Impairment questionnaire. Multivariate regression analysis modelled the relationship of care recipient/caregiver characteristics with caregiver HRQoL and productivity.

RESULTS: Data were provided by 365 caregivers; 114, 89, 75, 32, 29 and 26 in GvHD, PSP, ALS, MG, EoE and HD, respectively. Care recipients' mean (standard deviation [SD]) age was 58.7 (15.6) years, 59% were male and 23% had both professional and non-professional caregivers. Patients' mean (SD) EuroQol visual analogue scale (EQ VAS) score was 50.9 (23.3) and mean EQ-5D utility was 0.460 (0.350). Caregivers' mean age was 55.8 (13.8) years, 66% were female. Caregivers' EQ-5D-5L indicated their greatest problems in anxiety/depression. Overall, 45% of caregivers were employed, mostly part-time. In the past 7 days, mean (SD) caregiver absenteeism was 5.2% (13.1%), presenteeism was 28.0% (23.7%), and activity impairment was 43.1% (27.2%). Regressions identified multiple significant associations with caregivers' HRQoL and productivity. Caregivers' HRQoL (EQ-5D utility and EQ VAS) was associated with care recipients' EQ-5D utility and caregivers' age. Outcomes relating to caregivers' employment and productivity (hours spent caring, employment status, hours in employment, hours of employment missed, absenteeism, presenteeism, work impairment and activity impairment) were most frequently associated with care recipients' EQ-5D utility, caregivers' age and sex, caregiver living with the care recipient, the presence of a professional caregiver, and the care recipient having HD.

CONCLUSIONS: The substantial burden of providing non-professional caregiving to adults with rare diseases is associated with multiple factors. Interventions improving care recipient HRQoL could enhance caregiver HRQoL and productivity.}, } @article {pmid40480719, year = {2025}, author = {Fuentes, CA and Montoya, D and Öztop, M and Rojas-Rioseco, M and Bravo, M and González, F and Castillo, RDP}, title = {Interval resonance analysis (InRA): A versatile tool for automated untargeted [1]H NMR fingerprinting - A case study in sugar beet field authentication.}, journal = {Analytica chimica acta}, volume = {1363}, number = {}, pages = {344175}, doi = {10.1016/j.aca.2025.344175}, pmid = {40480719}, issn = {1873-4324}, mesh = {*Beta vulgaris/chemistry ; *Proton Magnetic Resonance Spectroscopy/methods ; Least-Squares Analysis ; Software ; Automation ; Multivariate Analysis ; Algorithms ; }, abstract = {BACKGROUND: The extraction of relevant information from proton nuclear magnetic resonance ([1]H NMR) spectra through preprocessing and multivariate analysis requires integrating multiple software tools and extensive manual intervention, compromising efficiency and reproducibility when the technique is used. Consequently, the development of automated, versatile, and reliable methodologies has become imperative to streamline workflows, improve analytical performance, and broaden the applicability of multivariate methods for the analysis of diverse sample types and experimental conditions.

RESULTS: This work presents the development and application of Interval Resonance Analysis (InRA), an alternative software tool focused on [1]H NMR multivariate analysis. InRA includes a novel algorithm for resonance signal detection (intervals), specifically designed to operate with flexibility across diverse [1]H NMR spectra. All intervals are integrated using multivariate curve resolution with alternating least squares (MCR-ALS) and analyzed by exploratory analysis. The performance of InRA was tested by evaluating the [1]H NMR spectra of hydrophilic sugar beet root extracts cultivated in three different fields and their discrimination by partial least squares - discriminant analysis (PLS-DA). The workflow provided by InRA yielded consistent results regarding the distribution of samples according to their field, enabling the identification of subtle sources of variation and achieving classification accuracies ≥ 88.9 %.

SIGNIFICANCE: The proposed methodology represents an advancement in the multivariate analysis of [1]H NMR spectra for untargeted studies and enhances analytical efficiency by reducing manual intervention and reliance on analyst experience. InRA is versatile and can be applied to various sample types and analytical objectives, as it is not restricted by specific experimental conditions.}, } @article {pmid40480675, year = {2025}, author = {Reitzle, L and Rohmann, JL and Kurth, T and Audebert, HJ and Piccininni, M}, title = {External validation of risk prediction models for post-stroke mortality in Berlin.}, journal = {BMJ open}, volume = {15}, number = {6}, pages = {e089320}, pmid = {40480675}, issn = {2044-6055}, mesh = {Humans ; Male ; Female ; Aged ; Berlin/epidemiology ; Registries ; Risk Assessment/methods ; *Stroke/mortality ; Hospital Mortality ; Aged, 80 and over ; Middle Aged ; Risk Factors ; }, abstract = {OBJECTIVES: Prediction models for post-stroke mortality can support medical decision-making. Although numerous models have been developed, external validation studies determining the models' transportability beyond the original settings are lacking. We aimed to assess the performance of two prediction models for post-stroke mortality in Berlin, Germany.

DESIGN: We used data from the Berlin-SPecific Acute Treatment in Ischaemic or hAemorrhagic stroke with Long-term follow-up (B-SPATIAL) registry.

SETTING: Multicentre stroke registry in Berlin, Germany.

PARTICIPANTS: Adult patients admitted within 6 hours after symptom onset and with a 10th revision of the International Classification of Diseases discharge diagnosis of ischaemic stroke, haemorrhagic stroke or transient ischaemic attack at one of 15 hospitals with stroke units between 1 January 2016 and 31 January 2021.

PRIMARY OUTCOME MEASURES: We evaluated calibration (calibration-in-the-large, intercept, slope and plot) and discrimination performance (c-statistic) of Bray et al's 30-day mortality and Smith et al's in-hospital mortality prediction models. Information on mortality was supplemented by Berlin city registration office records.

RESULTS: For the validation of Bray et al's model, we included 7879 patients (mean age 75; 55.0% men). We observed 763 (9.7%) deaths within 30 days of stroke compared with 680 (8.6%) predicted. The model's c-statistic was 0.865 (95% CI: 0.851 to 0.879). For Smith et al's model, we performed the validation among 1931 patients (mean age 75; 56.2% men), observing 105 (5.4%) in-hospital deaths compared with the 92 (4.8%) predicted. The c-statistic was 0.891 (95% CI: 0.864 to 0.918). The calibration plots of both models revealed an underestimation of the mortality risk for high-risk patients.

CONCLUSIONS: Among Berlin stroke patients, both models showed good calibration performance for low and medium-risk patients and high discrimination while underestimating risk among high-risk patients. The acceptable performance of Bray et al's model in Berlin illustrates how a small number of routinely collected variables can be sufficient for valid prediction of post-stroke mortality.}, } @article {pmid40480424, year = {2025}, author = {Lin, CY and Wu, HC and Fu, RH and Weng, EF and Hsieh, WC and Su, TP and Wu, HE and Wang, SM}, title = {Sigma-1R-Pom121 axis preserves nuclear transport and integrity in poly-PR-induced C9orf72 ALS.}, journal = {Neurobiology of disease}, volume = {212}, number = {}, pages = {106992}, doi = {10.1016/j.nbd.2025.106992}, pmid = {40480424}, issn = {1095-953X}, mesh = {*Amyotrophic Lateral Sclerosis/metabolism/genetics/pathology ; Animals ; *Receptors, sigma/metabolism/genetics ; *C9orf72 Protein/genetics/metabolism ; Sigma-1 Receptor ; Mice ; Humans ; *Active Transport, Cell Nucleus/physiology ; *Nuclear Pore Complex Proteins/metabolism/genetics ; Activating Transcription Factor 3/metabolism ; Mice, Transgenic ; Disease Models, Animal ; }, abstract = {Nucleocytoplasmic transport disruption contributes to the pathogenesis of C9orf72-associated amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. Among the dipeptide repeat proteins translated from G4C2-repeat RNA, poly-PR is particularly toxic, compromising nuclear envelope integrity and transport. Here, we revealed that poly-PR reduced expression of the nucleoporin Pom121 in NSC-34 cells and in an AAV-mediated poly-PR42 mouse model, resulting in cytoplasmic mislocalization of the neuroprotective transcription factor ATF3 and nuclear envelope damage. Pom121 overexpression restored nuclear ATF3 localization and alleviated poly-PR-induced toxicity. We further identified Sigma-1 receptor (Sigma-1R) as a stabilizer of Pom121 that preserved nuclear integrity and ATF3 function under oxidative stress. Overexpression of Sigma-1R, Pom121, or ATF3 rescued poly-PR-induced cytotoxicity. Our findings defined a protective Sigma-1R/Pom121/ATF3 axis and suggested this pathway as a therapeutic target in C9orf72-linked ALS.}, } @article {pmid40480222, year = {2025}, author = {Oldani, EG and Reynolds Caicedo, KM and Spaeth Herda, ME and Sachs, AH and Chapman, EG and Kumar, S and Linseman, DA and Horowitz, S}, title = {The effect of G-quadruplexes on TDP43 condensation, distribution, and toxicity.}, journal = {Structure (London, England : 1993)}, volume = {33}, number = {8}, pages = {1294-1303.e5}, doi = {10.1016/j.str.2025.05.006}, pmid = {40480222}, issn = {1878-4186}, mesh = {*G-Quadruplexes ; Humans ; *DNA-Binding Proteins/metabolism/chemistry/genetics ; HEK293 Cells ; Oxidative Stress ; Mice ; Animals ; Protein Aggregates ; Protein Binding ; Saccharomyces cerevisiae/metabolism ; RNA/chemistry/metabolism ; }, abstract = {Many proteins implicated in neurodegenerative diseases (e.g., trans-active response DNA binding protein 43 kDa [TDP43]) interact with nucleic acids, including RNA G-quadruplexes (G4s). We here investigate whether RNA G4s play a role in TDP43 condensation in biophysical and cellular models. We find that G4s modulate TDP43 aggregation in vitro and condensation in multiple cell types, including yeast, HEK293T, and motor-neuron-like NSC-34 cells. In yeast cells, treatment with G4s causes increased TDP43 accumulation in cells before cellular death. In HEK293T cells expressing TDP43, incubation with G4-binding small molecules causes an increase in G4 stability that also stabilizes TDP43 and reduces TDP43 condensation induced by proteasomal or oxidative stress. Finally, in NSC-34 cells overexpressing exogenous TDP43, we show that G4s co-localize with TDP43 condensates under stress conditions, and treatment with G4-binding small molecules decreases TDP43-mediated toxicity. Together, these findings suggest exploring treating protein misfolding diseases by targeting specific RNA structures such as G4s.}, } @article {pmid40478288, year = {2025}, author = {Wilbert, D and Voigt, M and Jaeger, M}, title = {A process analyzer assembly for real-time automated near-infrared, Raman, and proton nuclear magnetic resonance spectroscopic monitoring enhanced by heterocovariance spectroscopy and chemometry applied to a Schiff base formation.}, journal = {Analytical and bioanalytical chemistry}, volume = {}, number = {}, pages = {}, pmid = {40478288}, issn = {1618-2650}, abstract = {Process analytical technology (PAT) plays a key role in enhancing the efficiency and resulting quality of chemical processes. Hitherto, suitable methods enable real-time analysis and provide meaningful and robust data and models. Spectroscopic techniques, e.g., vibrational or absorption, offer in situ insight into reaction progress but may require advanced data analysis to interpret the complex spectra. In this study, inline and online monitoring by spectroscopic techniques was applied to a Schiff base formation as an illustrative example and enhanced by data analysis. Two-dimensional heterocorrelation spectroscopy was used to identify and select relevant spectral regions. The results allowed data reduction and data fusion for model building and process description. First, qualitative process representation was achieved through principal component analysis (PCA). Quantitative prediction models were then developed using multivariate curve resolution-alternating least squares (MCR-ALS) with evolving factor analysis (EFA), partial least squares (PLS), and supporting vector regression (SVR) analysis. The low- and mid-level data fusion based on the spectroscopic data and the multivariate models enabled the development of accurate predictive models, with the best prediction achieved by PLS models from low-level data fusion. The results demonstrate the strength of the combination of spectroscopy, multivariate data analysis, and-in the field of PAT rarely exploited-heterocovariance transformation and data fusion to obtain process understanding and reaction models. The methodology may provide further contributions to automatable process control in industrial applications.}, } @article {pmid40476320, year = {2025}, author = {Bombaci, A and De Marco, G and Casale, F and Salamone, P and Marchese, G and Fuda, G and Calvo, A and Chiò, A}, title = {Peripherin: A Novel Early Diagnostic and Prognostic Plasmatic Biomarker in Amyotrophic Lateral Sclerosis.}, journal = {European journal of neurology}, volume = {32}, number = {6}, pages = {e70241}, pmid = {40476320}, issn = {1468-1331}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/blood/diagnosis ; Male ; Female ; Middle Aged ; *Peripherins/blood ; Biomarkers/blood ; Aged ; Prognosis ; Disease Progression ; Adult ; Early Diagnosis ; }, abstract = {BACKGROUND: Motor neuron diseases (MND) are heterogeneous and complex neurodegenerative disorders. Biomarkers could facilitate early diagnosis, prognosis determination, and patient stratification. Among the most studied biomarkers are neurofilaments, with peripherin (PRPH), a specific type predominantly expressed in the peripheral nervous system, gaining attention. To date, no studies have evaluated PRPH in human plasma.

METHODS: Sandwich-ELISA was used to quantify plasma peripherin from 120 MND (100 ALS, 4 PMA, 15 PLS), 73 MND-mimics, and 38 healthy-controls (HCs). Plasma was collected at diagnosis or some months earlier. 41 ALS were evaluated longitudinally. ALSFRSr, MRC, spirometry, genetic tests, disease progression rate (PR), blood examinations, and neuropsychological tests were performed. Statistical analyses included Kruskal-Wallis, Mann-Whitney, Cox regression, and Kaplan-Meier curves.

RESULTS: Plasma PRPH levels differed significantly among groups (p < 0.0001), showing higher values in MND participants than MND mimics and HCs. Moreover, PRPH levels were elevated in PLS compared with HSP patients (p = 0.0001). Differences persisted after adjusting for age and sex. ROC curve demonstrated that PRPH discriminated MND from MND mimics (AUC = 0.85). Elevated PRPH correlated positively with ALSFRSr and lower motor neuron index, whereas inversely with disease progression rate. Higher PRPH levels at the beginning of the disease were associated with longer survival.

DISCUSSION: Plasma PRPH is raised in MND, particularly ALS, from the earliest stages, distinguishing MND from mimics and correlating with clinical parameters and survival. This suggests PRPH may reflect an endogenous response of lower motor neuron to injury. Further multicenter studies are required to refine the diagnostic and prognostic utility of PRPH in MND.}, } @article {pmid40476303, year = {2025}, author = {Mustafa, MA and Bansal, P and Pallavi, MS and Panigrahi, R and Nathiya, D and Kumar, S and Al-Hasnaawei, S and Chauhan, AS and Singla, S}, title = {Exploring the Role of NLRP3 in Neurodegeneration: Cutting-Edge Therapeutic Strategies and Inhibitors.}, journal = {Developmental neurobiology}, volume = {85}, number = {3}, pages = {e22982}, doi = {10.1002/dneu.22982}, pmid = {40476303}, issn = {1932-846X}, mesh = {*NLR Family, Pyrin Domain-Containing 3 Protein/metabolism/antagonists & inhibitors ; Humans ; Animals ; *Neurodegenerative Diseases/metabolism/drug therapy ; *Inflammasomes/metabolism ; *Neuroprotective Agents/pharmacology ; }, abstract = {Inflammasomes, particularly the NLRP3 inflammasome, play a pivotal role in mediating neuroinflammation in neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), and Huntington's disease (HD). Recent findings indicate that the activation of the NLRP3 inflammasome in microglia and astrocytes triggers the release of pro-inflammatory cytokines, including IL-1β and IL-18, which contribute to chronic inflammation and neuronal damage. This process accelerates neurodegeneration and exacerbates disease progression. Misfolded protein aggregates, mitochondrial dysfunction, and oxidative stress are key factors in the pathological activation of the NLRP3 inflammasome in these diseases. Recent studies have highlighted that targeting the NLRP3 inflammasome, either through direct inhibitors like MCC950 or natural compounds such as oridonin and β-hydroxybutyrate, shows promise in mitigating neuroinflammation and protecting neuronal integrity. These inhibitors have demonstrated neuroprotective effects in animal models of AD, PD, and MS, presenting a new therapeutic approach for halting disease progression. However, the complexity of NLRP3 regulation requires further investigation to balance its inflammatory and protective roles. This review examines the recent advancements in NLRP3 inflammasome research and discusses potential strategies for modulating inflammasome activity to slow or prevent the progression of neurodegenerative diseases.}, } @article {pmid40475252, year = {2025}, author = {Seyedi Asl, FS and Malverdi, N and Ataei Kachouei, FS and Zarei, F and Ghiabi, S and Baziyar, P and Nabi-Afjadi, M}, title = {Inhibitory effect of Fisetin against the aggregation process of SOD1 E100K mutant: computer-based drug design as a potential therapeutic for ALS disease.}, journal = {Frontiers in chemistry}, volume = {13}, number = {}, pages = {1569777}, pmid = {40475252}, issn = {2296-2646}, abstract = {Protein misfolding and aggregation in superoxide dismutase 1 (SOD1) are linked to the neurodegenerative disease amyotrophic lateral sclerosis (ALS). SOD1 mutations have a significant role in the pathophysiology and fast behavior of protopathic proteins in ALS illness. The E100K mutation may be useful in uncovering the pathogenic mechanism of SOD1 associated with ALS. According to several studies, giving small molecule inhibitors made from polyphenolic flavonoid compounds may be a viable treatment strategy for neurological conditions. Using molecular docking and MD simulations, we have identified a potential flavonoid drug that may successfully inhibit SOD1's amyloidogenic activity. Puerarin, Fisetin, and Peonidin provided intriguing pharmacological hints during the initial screening of flavonoids. The Fisetin-E100K complex had a larger residual energy contribution and substantial binding than other flavonoid compounds. The findings showed that, unlike other materials, Fisetin increased the structural stability, hydrophobicity, and flexibility of the mutant while reducing the amount of β-sheets. Furthermore, to distinguish aggregation in the mutant (unbound/bound) states, we displayed modifications in the free energy landscape (FEL). As a result, Fisetin was identified as having therapeutic potential against the E100K, which might make it a viable pharmacological option for the creation of inhibitors that lower the chance of ALS death.}, } @article {pmid40474686, year = {2025}, author = {Rothstein, J and Genge, A and De Silva, S and Zinman, L and Chum, M and Chio, A and Sobue, G and Aoki, M and Yoshino, H and Doyu, M and Selness, D and Todorovic, V and Sasson, N and Hirai, M and Takahashi, F and Salah, A and Wamil, A and Apple, S}, title = {Efficacy and Safety of Once Daily Dosing vs. Approved On/Off Dosing of Edaravone Oral Suspension Up to 48 Weeks in Patients With Amyotrophic Lateral Sclerosis (Study MT-1186-A02).}, journal = {Muscle & nerve}, volume = {72}, number = {3}, pages = {433-442}, pmid = {40474686}, issn = {1097-4598}, support = {//Mitsubishi Tanabe Pharma America Inc./ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy ; *Edaravone/administration & dosage ; Male ; Female ; Middle Aged ; Double-Blind Method ; Aged ; Administration, Oral ; Treatment Outcome ; *Free Radical Scavengers/administration & dosage/adverse effects/therapeutic use ; Adult ; Drug Administration Schedule ; Suspensions ; }, abstract = {INTRODUCTION/AIMS: An On/Off dosing regimen of intravenous (IV) edaravone and edaravone oral suspension is approved in the US for the treatment of amyotrophic lateral sclerosis (ALS). Placebo-controlled clinical trials showed IV edaravone slows the rate of physical functional decline. This study evaluated whether investigational daily dosing displayed superior efficacy vs. approved on/off dosing of edaravone oral suspension, and assessed safety and tolerability, over 48 weeks in patients with ALS.

METHODS: Study MT-1186-A02 (NCT04569084) was a multicenter, phase 3b, double-blind, parallel group, superiority study that randomized patients to edaravone oral suspension (105-mg dose) administered Once Daily or the same edaravone oral suspension dose administered according to the approved On/Off regimen including placebo to mimic daily drug dosing. Patients had definite or probable ALS, baseline forced vital capacity ≥ 70%, and baseline disease duration ≤ 2 years. The primary endpoint was a combined assessment of function and survival (CAFS) at week 48, which included change in ALS Functional Rating Scale-Revised (ALSFRS-R) and time to death.

RESULTS: CAFS at week 48 indicated Once Daily dosing did not show a statistically significant difference vs. approved on/off dosing (p = 0.777). Both dosing regimens provided comparable change from baseline ALSFRS-R total score to week 48 (least squares mean difference: 0.27 [95% CI -1.43 to 1.97]). Edaravone oral suspension was well tolerated, and no new safety concerns were identified in either group.

DISCUSSION: Daily edaravone oral suspension did not show superiority and had equivalent safety and tolerability vs. the approved On/Off regimen, reinforcing the appropriateness of the approved dosing regimen.}, } @article {pmid40473629, year = {2025}, author = {Li, Y and Fang, J and Ding, Y and Zhang, X and Liu, Y and Qiu, W and Xu, H and Kang, Y and Chen, J and Gao, Y and Zhao, YG and Yang, P and Wang, B and Tian, W and Chen, Y and Bi, W and Zhang, P}, title = {β-propeller protein-associated neurodegeneration protein WDR45 regulates stress granule disassembly via phase separation with Caprin-1.}, journal = {Nature communications}, volume = {16}, number = {1}, pages = {5227}, pmid = {40473629}, issn = {2041-1723}, support = {20240484503//Beijing Nova Program/ ; 7244365//Natural Science Foundation of Beijing Municipality (Beijing Natural Science Foundation)/ ; 32471202//National Natural Science Foundation of China (National Science Foundation of China)/ ; 32270856//National Natural Science Foundation of China (National Science Foundation of China)/ ; }, mesh = {Humans ; *Stress Granules/metabolism ; RNA Recognition Motif Proteins/metabolism/genetics ; *Cell Cycle Proteins/metabolism/genetics ; *Neurodegenerative Diseases/genetics/metabolism/pathology ; *Carrier Proteins/metabolism/genetics ; Neurons/metabolism ; Induced Pluripotent Stem Cells/metabolism ; Poly-ADP-Ribose Binding Proteins/metabolism/genetics ; RNA Helicases/metabolism/genetics ; Animals ; Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology ; Mutation ; Mice ; HEK293 Cells ; Phase Separation ; DNA Helicases ; }, abstract = {β-propeller protein-associated neurodegeneration (BPAN) is a rare X-linked neurodegenerative disorder caused by mutations in the WDR45 gene, yet its molecular mechanisms remain poorly understood. Here, we identify a role for WDR45 in stress granule (SG) disassembly, mediated through its phase separation with Caprin-1. We demonstrate that WDR45 forms gel-like condensates via its WD5 domain, which competitively displaces G3BP1 from Caprin-1 to promote SG disassembly. BPAN-associated WDR45 mutations impair condensate formation and Caprin-1 interaction, leading to delayed SG disassembly, which correlates with earlier disease onset. WDR45 depletion also exacerbates amyotrophic lateral sclerosis-associated pathological SGs, highlighting its broader relevance to neurodegenerative diseases. Using iPSC-derived midbrain neurons from a BPAN patient, we demonstrate delayed SG recovery, directly linking WDR45 dysfunction to neurodegeneration. These findings establish WDR45 as a critical regulator of SG dynamics, uncover a potential molecular basis of BPAN pathogenesis, and identify therapeutic targets for neurodegenerative diseases associated with SG dysregulation.}, } @article {pmid40473505, year = {2025}, author = {Song, W and Huang, Q and Jiang, Z}, title = {Clinical efficacy of athletic taping-assisted physiotherapy for plantar fasciitis: A systematic evaluation and meta-analysis.}, journal = {Foot and ankle surgery : official journal of the European Society of Foot and Ankle Surgeons}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.fas.2025.05.013}, pmid = {40473505}, issn = {1460-9584}, abstract = {BACKGROUND: Plantar fasciitis is a common sports injury with long-term chronic pain in the heel as the main symptom, and athletic taping has achieved certain therapeutic effects to improve it, but the clinical efficacy of the problem is still controversial, which was evaluated by Meta-analysis to evaluate the clinical efficacy of the athletic taping technique on patients with plantar fasciitis.

METHODS: The Cochrane Library, Embase, PubMed, Web of Science, CNKI, Wanfang, and Vip databases were searched by computer for randomized controlled trial on the clinical efficacy of exercise taping in patients with PF from the time of construction to 1 September 2024, and the PRISMA 2020 checklist was strictly followed. Quality was assessed using the cochrane 2.0 randomized controlled trials scale by two independent reviewers. Endings were meta-analysis using RevMan 5.4.1 analysis software to analyse the data.

RESULTS: Eleven randomized controlled trial with a total of 395 patients were included. On VAS scores, KT effectively reduced VAS pain scores (MD=-0.79,95 % CI -1.10,-0.48, P < 0.00001); on AOFAS scores, KT improved AOFAS function scores (MD=6.58, 95 % CI 5.03,8.13, P < 0.00001) and the results remained consistent across intervention durations; on plantar fascia thickness measurements, KT significantly reduced plantar fascia thickness (MD=-0.33, 95 % CI -0.56,-0.10, P = 0.005); on BBS scores, KT significantly improved BBS scores [MD= 4.75, 95 % CI (3.17, 6.32), P < 0.00001]; on FFI-FPS scores, KT effectively improved FFI-FPS scores [MD = -2.59, 95 % CI (-3.50, -1.69), P < 0.00001]; on FFI-FDS scores, there was a significant improvement on FFI-FDS scores; on FFI-ALS scores, KT had a significant improvement on the FFI-ALS score had a significant effect [MD= -11.03, 95 % CI (-14.79, -7.27), P < 0.00001]; and on VAS scores after follow-up, the pain relief effect was sustained (MD=-1.03, 95 % CI -1.21, -0.85, P < 0.00001).

CONCLUSION: Based on the available evidence, preliminary analyses suggest that KT combined with conventional rehabilitation may have some advantages in improving pain, ankle-hindfoot function, and plantar fascia thickness in patients with plantar fasciitis, and some of the efficacy is short-term sustained. However, due to the heterogeneity and sample size of the included studies, the above conclusions need to be further validated by more high-quality studies.}, } @article {pmid40473122, year = {2025}, author = {Mueller, KA and Suneby, EG and Ferola, MH and Moreno, AJ and Kidd, JD and Thompson, K and Vieira, FG and Valdez, G and Hatzipetros, T}, title = {Comprehensive characterization and validation of the Prp-hPFN1[G118V] mouse model: Guidelines for preclinical therapeutic testing for ALS.}, journal = {Neurobiology of disease}, volume = {212}, number = {}, pages = {106975}, doi = {10.1016/j.nbd.2025.106975}, pmid = {40473122}, issn = {1095-953X}, mesh = {Animals ; *Amyotrophic Lateral Sclerosis/genetics/pathology/physiopathology/drug therapy ; *Disease Models, Animal ; Mice ; Mice, Transgenic ; Female ; *Profilins/genetics ; Male ; Humans ; Drug Evaluation, Preclinical/methods ; Motor Neurons/pathology ; Spinal Cord/pathology ; Neuromuscular Junction/pathology ; }, abstract = {The hPFN1[G118V] mouse model, overexpressing mutant human profilin1 linked to a rare form of ALS, was comprehensively characterized to assess its suitability for preclinical drug testing. Using a large cohort of nearly 250 transgenic and wild-type mice in a longitudinal study, we combined behavioral, electrophysiological, and neuropathological assessments to define the chronology of pathological events and assess inherent subject variability. The early stage of the disease in this model was characterized by elevated plasma neurofilament light chain levels, an effect that persisted and progressed throughout the course of the disease, followed by spinal cord neuroinflammation, suggesting that axonal pathology is the initiating event. The middle stage of the disease involved progressive neuromuscular decline, including reductions in compound muscle action potential (CMAP) and grip strength, accompanied by neuromuscular junction degeneration. The end-stage of the disease was characterized by the onset of visible changes such as weight loss, gait abnormalities and hindlimb paresis that quickly progressed to paralysis. At end-stage we also observed spinal motor neuron loss and TDP-43 pathology. The average humane endpoint was 213 days for females and 237 days for males. Our findings demonstrate that hPFN1[G118V] mice recapitulate key ALS features with moderate disease progression and a reproducible disease course, making them a valuable model for therapeutic testing. Recommendations are provided to optimize study design for preclinical testing, emphasizing survival duration as the primary endpoint, with CMAP and plasma NFL as key secondary readouts.}, } @article {pmid40470490, year = {2025}, author = {Ren, S and Che, X and Hu, S and Feng, X and Zhang, J and Shi, P}, title = {The effect of exercise intervention on amyotrophic lateral sclerosis: a systematic review and meta-analysis.}, journal = {Frontiers in neurology}, volume = {16}, number = {}, pages = {1499407}, pmid = {40470490}, issn = {1664-2295}, abstract = {OBJECTIVE: Quantitative evaluation of the effect of exercise intervention in amyotrophic lateral sclerosis (ALS).

METHODS: The CNKI, WOS, PubMed, and Scopus databases were searched by computer, and randomized controlled trials (RCTs) of exercise intervention in ALS were screened out according to the inclusion and exclusion criteria of the PICOS principle. Stata 12.0 software was used for statistical analysis.

RESULTS: A total of 12 RCTs including 430 participants were included. Meta-analysis results show that exercise intervention can significantly improve the overall function, walking test (WT) distance and maximum expiratory pressure (MEP) of ALS patients (p < 0.05). However, exercise interventions did not show significant effects on fatigue, maximum inspiratory pressure (MIP), forced vital capacity (FVC), and peak expiratory flow (PEF) in ALS patients (p > 0.05). Subgroup analysis showed that resistance exercise is the most effective intervention for improving the function of ALS patients, while aerobic exercise is the most effective intervention for improving FVC in ALS patients.

CONCLUSION: Exercise intervention in ALS has a positive effect, but due to the small number of included studies and possible heterogeneity, risk of bias and sensitivity issues, further research is needed.}, } @article {pmid40469844, year = {2025}, author = {Shen, D and Yang, X and He, D and Zhang, K and Liu, S and Sun, X and Li, J and Cai, Z and Liu, M and Zhang, X and Liu, Q and Cui, L}, title = {Genetic analysis of ERBB4 gene in Chinese patients with amyotrophic lateral sclerosis: a single-center study and systematic review of published literature.}, journal = {Frontiers in aging neuroscience}, volume = {17}, number = {}, pages = {1584541}, pmid = {40469844}, issn = {1663-4365}, abstract = {BACKGROUND: Rare ERBB4 variants have been implicated in amyotrophic lateral sclerosis (ALS), but their prevalence and clinical significance remain poorly understood, particularly across different ethnic populations.

METHODS: We performed genetic screening of ERBB4 in 1627 Chinese ALS patients using whole-exome sequencing. A systematic review and meta-analysis of the published literature were conducted to evaluate the global frequency of ERBB4 variants and their clinical correlations.

RESULTS: We identified 14 missense variants and 6 splice region variants in 23 unrelated patients, with four variants classified as damaging (p.R782P, p.M799T, p.R847C, and p.S997R). The splice variant c.1490-3C > T, associated with a 50% reduction in ERBB4 mRNA expression, was maternally inherited by a male ALS patient, while its presence in his asymptomatic mother suggests the involvement of potential genetic modifiers. ERBB4 variant carriers demonstrated earlier disease onset compared to non-carriers (46.9 ± 10.3 vs. 52.6 ± 11.2 years; p = 0.015), though survival duration remained comparable. Meta-analysis revealed a pooled ERBB4 variant frequency of 0.83% (95% CI, 0.56-1.10%) in ALS patients globally, with notable ethnic differences (1.36% in Chinese, 0.66% in European, and 1.44% in American populations).

CONCLUSION: Our findings establish the prevalence of ERBB4 variants in ALS across different populations and suggest their potential role as disease modifiers, particularly affecting the age of onset. The ethnic variation in mutation frequency highlights the importance of population-specific genetic screening strategies in ALS.}, } @article {pmid40468914, year = {2025}, author = {Cao, Y and Yuan, B and Jiang, X and Xie, C and Wu, D and Zhang, Z}, title = {Quantification of Skeletal Muscle at the First Lumbar Level for Prognosis in Amyotrophic Lateral Sclerosis.}, journal = {Journal of cachexia, sarcopenia and muscle}, volume = {16}, number = {3}, pages = {e13827}, pmid = {40468914}, issn = {2190-6009}, support = {81830040//National Natural Science Key Foundation of China/ ; }, mesh = {Aged ; Female ; Humans ; Male ; Middle Aged ; *Amyotrophic Lateral Sclerosis/mortality/pathology/diagnostic imaging/diagnosis ; *Lumbar Vertebrae/diagnostic imaging ; *Muscle, Skeletal/diagnostic imaging/pathology ; Prognosis ; Tomography, X-Ray Computed ; }, abstract = {BACKGROUND: Skeletal muscle parameters at the first lumbar vertebra (L1) level on computed tomography (CT) are common indicators for muscle mass. However, their relationship with the severity and prognosis of amyotrophic lateral sclerosis (ALS) patients remains unclear.

METHODS: This cohort study included ALS patients who underwent chest CT scans between January 2018 and January 2022 and healthy controls (HCs) matched for gender and age. Overall survival (OS) was determined from the date of chest CT to death, tracheal intubation or 1 January 2024. Using ImageJ software, skeletal muscle area and density (L1 SMA/SMD), skeletal muscle index (L1 SMI), paraspinal muscle area and density (L1 PMA/PMD) and subcutaneous fat area and density (L1 SFA/SFD) at L1 were quantified. The relationships between the quantified muscle parameters and both King's clinical stages and the Revised ALS Functional Rating Scale (ALSFRS-R) were analysed. The Cox proportional hazard model was used to evaluate the hazard ratio (HR) of skeletal muscle parameters as risk factors for outcome events, and to construct a nomogram.

RESULTS: Muscle parameters in ALS patients (n = 102; 36.27% female; mean age, 60.85 ± 10.58 years) were significantly lower compared with HCs (p < 0.001). L1 SMD (p = 0.047) and L1 PMD (p = 0.003) both differed significantly across the King's clinical stages. ALSFRS-R scores correlated with L1 SMA (r = 0.35, p < 0.001), L1 SMI (r = 0.34, p < 0.001), L1 PMA (r = 0.27, p = 0.007) and L1 PMD (r = 0.27, p = 0.007). Multivariate Cox regression analysis revealed that L1 SMA (HR = 0.96, 95% confidence interval [CI] = 0.94-0.98, p = 0.001), L1 SMD (HR = 0.92, 95% CI = 0.88-0.96, p < 0.001) and L1 PMA (HR = 1.06, 95% CI = 1.01-1.11, p = 0.022) significantly influenced ALS survival, with area under the curves (AUCs) of 0.687 and 0.851 for 1- and 3-year OS prediction. The consistency index (C-index) for the nomogram was 0.72 (95% CI = 0.641-0.793).

CONCLUSIONS: Skeletal muscle parameters at L1 level on CT are significantly associated with clinical severity and prognosis in ALS.

TRIAL REGISTRATION: Chinese Clinical Trial Registration Center: ChiCTR230078702.}, } @article {pmid40468389, year = {2025}, author = {Rummens, J and Da Cruz, S}, title = {RNA-binding proteins in ALS and FTD: from pathogenic mechanisms to therapeutic insights.}, journal = {Molecular neurodegeneration}, volume = {20}, number = {1}, pages = {64}, pmid = {40468389}, issn = {1750-1326}, support = {G064721N//Fonds Wetenschappelijk Onderzoek/ ; 1S15218N//Fonds Wetenschappelijk Onderzoek/ ; 962700//Muscular Dystrophy Association/ ; SAO-FRA 20230035//Alzheimer's Research Foundation/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism/pathology/genetics ; *Frontotemporal Dementia/metabolism/pathology/genetics ; *RNA-Binding Proteins/metabolism/genetics ; Animals ; DNA-Binding Proteins/metabolism ; RNA-Binding Protein FUS/metabolism ; }, abstract = {Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are devastating neurodegenerative disorders with overlapping clinical, genetic and pathological features. A large body of evidence highlights the critical role of RNA-binding proteins (RBPs) - in particular TAR DNA-binding protein 43 (TDP-43) and Fused in sarcoma (FUS) - in the pathogenesis of these diseases. These RBPs normally regulate various key aspects of RNA metabolism in the nervous system (by assembling into transient biomolecular condensates), but undergo cytoplasmic mislocalization and pathological aggregation in ALS and FTD. Furthermore, emerging evidence suggests that RBP-containing aggregates may propagate through the nervous system in a prion-like manner, driving the progression of these neurodegenerative diseases. In this review, we summarize the genetic and neuropathological findings that establish RBP dysfunction as a central theme in ALS and FTD, and discuss the role of disease-associated RBPs in health and disease. Furthermore, we review emerging evidence regarding the prion-like properties of RBP pathology, and explore the downstream mechanisms that drive neurodegeneration. By unraveling the complex role of RBPs in ALS and FTD, we ultimately aim to provide insights into potential avenues for therapeutic intervention in these incurable disorders.}, } @article {pmid40466410, year = {2025}, author = {Guillen-Sola, A and Bertran-Recasens, B and Martinez-Llorens, J and Balaña, A and Villatoro, M and Rubio, MA}, title = {[Use of tongue pressure to determine the indication for instrumental swallowing assessment in patients with spinal ALS].}, journal = {Rehabilitacion}, volume = {59}, number = {3}, pages = {100917}, doi = {10.1016/j.rh.2025.100917}, pmid = {40466410}, issn = {1578-3278}, abstract = {OBJECTIVE: Systematic swallowing assessment in amyotrophic lateral sclerosis (ALS) is essential, as approximately 85% of patients will develop dysphagia, and 8% of these cases may remain clinically silent. Although instrumental diagnostic tools exist, they are not always accessible. Recent studies suggest that lingual pressure measurements may be valuable for early detection of bulbar dysfunction. This study aims to establish lingual pressure cutoff points for early screening of such dysfunction.

DESIGN: Transversal study based on prospectively collected data from patients with spinal-onset ALS at the Motor Neuron Unit, Hospital del Mar (Barcelona).

MATERIALS AND METHODS: A total of 58 patients were included. Anterior (PA) and posterior (PP) lingual pressures were measured using the IOPI system and analyzed alongside the ALSFRS-R scale. Statistical analysis included descriptive statistics, Spearman correlation, and ROC curve analysis (SPSS v25).

RESULTS: A moderate correlation was found between lingual strength and ALSFRS-R scores (PA: r=.634, P<.001; PP: r=.539, P<.001). Identified cutoff values: PA: 39.5kPa (AUC=.766; 95%CI: .700-.831; P<.001), sensitivity 64.6%, specificity 76.4%. PP: 37.0kPa (AUC=.726; 95%CI: .653-.799; P<.001), sensitivity 55.1%, specificity 72.2%.

CONCLUSION: In spinal-onset ALS, a moderate correlation exists between global functionality and lingual pressures. Cutoff points of PA=39.5kPa and PP=37.0kPa are proposed for early screening of bulbar dysfunction.}, } @article {pmid40465292, year = {2025}, author = {Chourpiliadis, C and Lovik, A and Ingre, C and Press, R and Samuelsson, K and Valdimarsdottir, U and Fang, F}, title = {Use of Common Psychiatric Medications and Risk and Prognosis of Amyotrophic Lateral Sclerosis.}, journal = {JAMA network open}, volume = {8}, number = {6}, pages = {e2514437}, pmid = {40465292}, issn = {2574-3805}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/epidemiology/diagnosis ; Male ; Female ; Case-Control Studies ; Middle Aged ; Sweden/epidemiology ; Aged ; Prognosis ; *Antidepressive Agents/adverse effects/therapeutic use ; *Hypnotics and Sedatives/adverse effects/therapeutic use ; *Mental Disorders/drug therapy ; *Anti-Anxiety Agents/adverse effects/therapeutic use ; Risk Factors ; Registries ; Disease Progression ; *Psychotropic Drugs/adverse effects/therapeutic use ; }, abstract = {IMPORTANCE: Although several studies have shown an increased risk of subsequent amyotrophic lateral sclerosis (ALS) diagnosis for individuals with a history of psychiatric disorders, the evidence of an association between use of common psychiatric medications and ALS is scarce and inconclusive.

OBJECTIVE: To examine whether there is an association of prescribed use of common psychiatric medications, namely anxiolytics, hypnotics and sedatives, and antidepressants, with the risk and disease progression of ALS.

This nationwide register-based case-control study was conducted in Sweden among all patients diagnosed with ALS from January 1, 2015, to July 1, 2023, according to the Swedish Motor Neuron Disease Quality Registry, who were age- and sex-matched with as many as 5 individuals with no ALS as well as their full siblings and spouses. Patients with ALS were followed up for a median (IQR) of 1.33 (0.64-2.37) years after diagnosis.

EXPOSURES: At least 2 prescriptions of the studied psychiatric medications before ALS diagnosis.

MAIN OUTCOMES AND MEASURES: The risk of ALS diagnosis associated with prediagnostic prescribed use of common psychiatric medications was estimated using conditional logistic regression models, comparing patients with ALS with population or relative control participants. Patients with ALS were followed up from diagnosis to assess the association of prediagnostic prescribed use of common psychiatric medications with disease progression. The association of mortality (or use of invasive ventilation) with the use of common psychiatric medications was estimated with a joint longitudinal-survival model accounting for the longitudinal changes of ALS Functional Rating Scale-Revised (ALSFRS-R) in the time-to-event analysis.

RESULTS: Among the 1057 case participants and 5281 population control participants, the mean (SD) age at diagnosis of the case participants (ie, date of selection of the control participants) was 67.5 (11.5) years, and 3363 (53.1%) were male. In the population comparison, prescribed use of common psychiatric medications across all studied time windows before ALS diagnosis was associated with a higher risk of ALS (eg, among individuals prescribed hypnotics and sedatives 0-1 year before diagnosis: odds ratio [OR], 6.10; 95% CI, 3.77-9.88; prescribed anxiolytics 1-5 years before diagnosis: OR, 1.60; 95% CI, 1.15-2.23; prescribed antidepressants >5 years before diagnosis: OR, 1.21; 95% CI, 1.02-1.44). Excluding the year before diagnosis from the analysis, prescribed use of anxiolytics (OR, 1.34; 95% CI, 1.12-1.60), hypnotics and sedatives (OR, 1.21; 95% CI, 1.02-1.43), or antidepressants (OR, 1.26; 95% CI, 1.06-1.49) was associated with an increased risk of ALS. Similar results were noted in the comparison with relative control participants, partially alleviating the concern on familial confounding, with the exception of hypnotics and sedatives. Shorter survival was demonstrated among patients with ALS who had prediagnostic use of anxiolytics (hazard ratio [HR], 1.52; 95% CI, 1.12-2.05) or antidepressants (HR, 1.72; 95% CI, 1.30-2.29), compared with patients with ALS without such experience.

CONCLUSIONS AND RELEVANCE: In this case-control study, prescribed use of anxiolytics, hypnotics and sedatives, or antidepressants was associated with a higher subsequent risk of ALS. Prediagnostic use of such medications was also associated with a poor prognosis after ALS diagnosis.}, } @article {pmid40464816, year = {2025}, author = {Savran, Z and Baltaci, SB and Aladag, T and Mogulkoc, R and Baltaci, AK}, title = {Vitamin D and Neurodegenerative Diseases Such as Multiple Sclerosis (MS), Parkinson's Disease (PD), Alzheimer's Disease (AD), and Amyotrophic Lateral Sclerosis (ALS): A Review of Current Literature.}, journal = {Current nutrition reports}, volume = {14}, number = {1}, pages = {77}, pmid = {40464816}, issn = {2161-3311}, mesh = {Humans ; *Neurodegenerative Diseases/metabolism/drug therapy ; *Vitamin D/metabolism ; Multiple Sclerosis ; Alzheimer Disease ; Parkinson Disease ; Receptors, Calcitriol/metabolism ; Amyotrophic Lateral Sclerosis ; Oxidative Stress/drug effects ; Animals ; Cholecalciferol ; }, abstract = {PURPOSE OF REVIEW: This review explores the role of Vitamin D3 and its derivatives as inhibitors of pathological metabolic modifications in neurodegenerative diseases. The manuscript investigates how Vitamin D3 impacts neuronal calcium regulation, antioxidative pathways, immunomodulation, and neuroprotection during detoxification, beyond its known functions in intestinal, bone, and kidney calcium and phosphorus absorption, as well as bone mineralization.

RECENT FINDINGS: Recent studies have highlighted the synthesis of the active metabolite 1,25(OH)2D3 (vitamin D) in glial cells via the hydroxylation process of CY-P24A1, an enzyme in the cytochrome P450 system in the brain. The effects of vitamin D occur through the vitamin D receptor (VDR), a nuclear steroid receptor, which has been identified in various brain regions, including the cerebellum, thalamus, hypothalamus, basal ganglia, hippocampus, olfactory system, temporal, and orbital regions. Neurodegeneration is primarily associated with oxidative stress, protein aggregation, neuroinflammation, mitochondrial dysfunction, apoptosis, and autophagy changes, all of which Vitamin D and VDR are believed to influence. Vitamin D and VDR are recognized as both environmental and genetic factors in the etiopathogenesis of neurodegenerative diseases such as Multiple Sclerosis (MS), Parkinson's Disease (PD), Alzheimer's Disease (AD), and Amyotrophic Lateral Sclerosis (ALS). A deficiency in Vitamin D is postulated to have detrimental effects on the brain and other diseases throughout various stages of life. This review consolidates findings from clinical and experimental studies, as well as past publications, focusing on the implications of Vitamin D deficiency in these neurodegenerative conditions. Current articles published in PubMed were extensively considered for this review.}, } @article {pmid40464332, year = {2025}, author = {Naim, A and Farooqui, AM and Badruddeen, and Khan, MI and Akhtar, J and Ahmad, A and Islam, A}, title = {The Role of Kinases in Neurodegenerative Diseases: From Pathogenesis to Treatment.}, journal = {The European journal of neuroscience}, volume = {61}, number = {11}, pages = {e70156}, doi = {10.1111/ejn.70156}, pmid = {40464332}, issn = {1460-9568}, mesh = {Humans ; *Neurodegenerative Diseases/enzymology/drug therapy/metabolism ; Animals ; *Protein Kinases/metabolism ; Protein Kinase Inhibitors/therapeutic use ; }, abstract = {Neurodegenerative diseases are characterized by progressive neuronal loss and dysfunction, with protein kinases playing crucial roles in their pathogenesis. This article explores the involvement of protein kinases in these disorders, focusing on their contributions to disease mechanisms, potential as therapeutic targets and challenges in developing effective treatments. In Alzheimer's disease, kinases such as CDK5, GSK3β and MARK4 are implicated in tau hyperphosphorylation and the formation of neurofibrillary tangles. Kinases also regulate amyloid-β processing and plaque formation. In Parkinson's disease, LRRK2, PINK1 and other kinases contribute to α-synuclein pathology, mitochondrial dysfunction and neuroinflammation. LRRK2 inhibitors and PROTACs have shown promise in preclinical models. Huntington's disease involves altered kinase activity, with CK2, GSK3 and MAPK pathways influencing mutant huntingtin toxicity and aggregation. Kinases are also implicated in less common neurodegenerative diseases, such as ALS and spinocerebellar ataxias. Despite the therapeutic potential of targeting kinases, challenges remain, including the complexity of kinase networks, blood-brain barrier permeability and the lack of robust biomarkers. Emerging technologies, such as covalent inhibitors, targeted protein degradation and combination therapies, offer new avenues for addressing these challenges and developing more effective treatments for neurodegenerative diseases.}, } @article {pmid40463912, year = {2025}, author = {Liu, T and Sun, W and Guo, S and Yuan, Z and Zhu, M and Lu, J and Chen, T and Qu, Y and Feng, C and Yang, T}, title = {Role of mitochondrial quality control in neurodegenerative disease progression.}, journal = {Frontiers in cellular neuroscience}, volume = {19}, number = {}, pages = {1588645}, pmid = {40463912}, issn = {1662-5102}, abstract = {Neurodegenerative diseases are a diverse group of neurological disorders, in which abnormal mitochondrial function is closely associated with their development and progression. This has generated significant research interest in the field. The proper functioning of mitochondria relies on the dynamic regulation of the mitochondrial quality control system. Key processes such as mitochondrial biogenesis, mitophagy, and mitochondrial dynamics (division/fusion) are essential for maintaining this balance. These processes collectively govern mitochondrial function and homeostasis. Therefore, the mitochondrial quality control system plays a critical role in the onset and progression of neurodegenerative diseases. This article provides a concise overview of the molecular mechanisms involved in mitochondrial biogenesis, mitophagy, and mitochondrial dynamics, explores their interactions, and summarizes current research progress in understanding the mitochondrial quality control system in the context of neurodegenerative diseases.}, } @article {pmid40463522, year = {2025}, author = {Cohen, Y and Sinai, I and Magen, I and Danino, MY and Wuu, J and Malaspina, A and Benatar, M and Hornstein, E}, title = {IsomiR Utility in ALS Prognostication.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, doi = {10.1101/2025.05.12.25325848}, pmid = {40463522}, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive motor neuron loss. IsomiRs are microRNA isoforms that arise from alternative processing or editing events during miRNA biogenesis. While isomiRs may carry distinct biological and clinical relevance, their potential as cell-free biomarkers in neurodegeneration remains largely unexplored. Intriguingly, loss of TAR DNA-binding protein 43 (TDP-43) nuclear function is a hallmark of disease and is known to impair isomiR expression. Here, we investigated the prognostic utility of plasma isomiRs in ALS, using next-generation sequencing. We profiled cell-free isomiRs in 154 ALS patients from a British cohort and identified higher levels of one isomiR, let-7g-5p.t, to be associated with longer survival. This finding was independently validated in an international ALS cohort of 200 patients and was in two orthogonal approaches. let-7g-5p.t prognostic utility was comparable to that of neurofilament light chain (NfL) or miR-181. These results establish isomiRs as a novel class of blood-based biomarkers in ALS with potential to refine prognostication in clinical trials for neurodegenerative diseases.}, } @article {pmid40462869, year = {2025}, author = {Acan, D and Cakar, BB and Karahan, E}, title = {Low anterior chamber volume as a risk factor in non-arteritic anterior ischemic optic neuropathy.}, journal = {Frontiers in ophthalmology}, volume = {5}, number = {}, pages = {1554279}, pmid = {40462869}, issn = {2674-0826}, abstract = {PURPOSE: This study aimed to compare the anterior chamber depth (ACD), anterior chamber volume (ACV), and iridocorneal angle (ICA) of the eyes of patients with non-arteritic anterior ischemic optic neuropathy (NAION) and normal eyes.

METHODS: In this cross-sectional study, 28 patients with NAION who were admitted to our institution were examined. Central corneal thickness (CCT), ACV, ACD, and ICA of all eyes were measured using corneal topography (Sirius, CSO, Italy). Axial lengths (ALs) were measured using an IOL-Master 500 (Carl Zeiss, Meditec). The eyes of these patients were compared with the eyes of 29 healthy individuals of similar age and gender.

RESULTS: The mean ALs of the eyes with NAION and those in the control group were not statistically different, measuring 22.95 ± 0.68 mm and 23.13 ± 0.80mm, respectively (p=0.651). While the average ACV was 137.93 ± 41.01 mm[3] in the control group, it was significantly lower at 117.86 ± 22.23 mm[3] in the patients with NAION (p=0.038). The mean ACD, ICA, and CCT values in the control and study groups were not statistically different, with 2.82 ± 0.57 mm and 2.64 ± 0.31 mm, 41.62 ± 6.99° and 40.14 ± 7.04°, and 542.48 ± 19.39µm and 544.68 ± 31.26 µm, respectively (p1 = 0.236, p2 = 0.693, and p3 = 0.959). No statistical differences were found between the eyes with NAION and their fellow eyes in terms of AL, CCT, ACD, ACV, and ICA (p>0.05).

CONCLUSION: Differences in anterior segment morphology were observed in eyes with NAION compared to healthy eyes. Decreased ACV may be a risk factor for NAION.}, } @article {pmid40462740, year = {2025}, author = {DeCastro, J and Mehta-Doshi, A and Liu, C and Ray, A and Aran, K}, title = {Red Blood Cell-Derived Exosomes as Mediators of Age-Related Neurodegeneration.}, journal = {Rejuvenation research}, volume = {28}, number = {4}, pages = {184-194}, pmid = {40462740}, issn = {1557-8577}, mesh = {*Exosomes/metabolism ; Animals ; MicroRNAs/genetics/metabolism ; *Neurodegenerative Diseases/genetics/pathology/blood ; *Aging/pathology/genetics ; *Erythrocytes/metabolism ; Mice ; Biomarkers/metabolism ; Mice, Inbred C57BL ; Male ; }, abstract = {Age-associated neurodegenerative diseases (NDDs), including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis, are marked by progressive degeneration of the nervous system. Current diagnostic approaches, such as neuroimaging and cerebrospinal fluid biomarkers, are invasive, costly, and lack early diagnostic reliability. Recent studies highlight the potential of extracellular vesicles, particularly exosomes, derived from erythrocytes or red blood cells (RBCs), as emerging indicators of aging and age-associated diseases. Exosomes carry noncoding RNA, lipid, and protein molecules, and modulate cellular pathways at distant sites, providing neuroprotective and anti-inflammatory effects. In this study, we isolated RBC-derived exosomes of young and old mice. MicroRNA sequencing analysis revealed differential expression of several miRNA species between young and old mice. We report an upregulation of miR-125a-5p and a downregulation of miR-302a-5p in old mice that are potentially linked to neurodegenerative pathways. This study underscores the potential of RBC-derived exosomes as noninvasive biomarkers for NDDs.}, } @article {pmid40462656, year = {2025}, author = {Gong, Z and Cao, R and Zhu, H}, title = {Exploring the Causal Association Between 91 Circulating Inflammatory Proteins and Neurodegenerative Diseases: A Bidirectional Two-Sample Mendelian Randomization and Bioinformatics Analysis.}, journal = {Brain and behavior}, volume = {15}, number = {6}, pages = {e70586}, pmid = {40462656}, issn = {2162-3279}, support = {2025JJ70054//Natural Science Foundation of Hunan Province/ ; }, mesh = {Humans ; Mendelian Randomization Analysis/methods ; Genome-Wide Association Study ; *Neurodegenerative Diseases/genetics/blood ; Computational Biology ; CD40 Antigens/genetics ; Polymorphism, Single Nucleotide ; Amyotrophic Lateral Sclerosis/genetics ; Quantitative Trait Loci ; Parkinson Disease/genetics ; Multiple Sclerosis/genetics ; Alzheimer Disease/genetics ; Inflammation/genetics ; }, abstract = {BACKGROUND: Circulating inflammatory proteins play a significant role in the pathogenesis of neurodegenerative diseases (NDDs). However, the precise causal relationship and the underlying mechanisms of their interaction remain elusive.

METHODS: Genome-wide association study (GWAS) data for 91 circulating inflammatory proteins were obtained from the GWAS Catalog. Additionally, GWAS data for Parkinson's disease (PD), Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), and ischemic stroke (IS) were acquired from the IEU Open GWAS Project. Four Mendelian randomization (MR) methods were employed to analyze causal effects, accompanied by sensitivity and pleiotropy analyses. Expression quantitative trait loci (eQTL) analyses for CD40 and MS-associated SNPs were performed. Transcriptomic data from the peripheral blood of MS patients were used to identify differentially expressed genes (DEGs) in relapsing-remitting MS (RRMS). RRMS patients were divided into two subgroups (C1 and C2) based on CD40 expression levels for comparative analysis. A single gene set enrichment analysis (GSEA) was conducted to investigate potential molecular mechanisms through which CD40 influences MS.

RESULTS: MR analyses indicated that CD40 ligand receptor (CD40) is associated with a reduced risk of MS (OR, 0.78; 95% CI, 0.72-0.84; PFDR = 8.75E-07). No statistically significant bidirectional causal relationships were found between other inflammatory proteins and PD, AD, ALS, or IS, and the findings were robust. Functional enrichment analysis revealed that these eQTLs primarily relate to transcriptional regulation, herpes simplex virus 1 (HSV-1) infection, and bile and fatty acid metabolism. In MS peripheral blood microarray data, CD40 is significantly downregulated in RRMS. Intergroup comparisons revealed elevated levels of resting memory CD4[+] T cells, activated NK cells, and neutrophils in C1, alongside increased autophagy, apoptosis, multiple immune responses, and upregulation of transforming growth factor-β (TGF-β) signaling pathways. Conversely, C2 exhibited higher levels of Tregs, resting NK cells, and activated dendritic cells, as well as upregulation in processes such as cholesterol homeostasis, glucose metabolism, and CD4/CD8 downregulation. Single-GSEA results suggest that CD40 promotes nucleotide metabolism, mitochondrial calcium ion transport, unfolded protein response (UPR), and adaptive immune regulation, while inhibiting androgen response and TGF-β signaling pathways, thereby influencing the progression of RRMS.

CONCLUSION: CD40 may exert neuroprotective effects in MS patients via diverse cellular and molecular pathways, potentially representing a novel target for MS intervention.}, } @article {pmid40462477, year = {2025}, author = {Shaka, Z and Mojtabavi, H and Taebi, M and Mahmoodi-Bakhtiari, B and Sarraf, P}, title = {Examining cognitive decline over time in Iranian ALS patients: Adapting successive versions B and C of the Edinburgh cognitive and behavioral screen to Persian.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {}, number = {}, pages = {1-11}, doi = {10.1080/21678421.2025.2509615}, pmid = {40462477}, issn = {2167-9223}, abstract = {OBJECTIVE: To adapt successive versions B and C of the Edinburgh Cognitive and Behavioral Screen (ECAS) into Persian and evaluate cognitive and behavioral changes over time in Iranian ALS patients.

METHODS: This study included 38 ALS patients in the ECAS-B group and 29 in the ECAS-C group, diagnosed between May 2021 and February 2023 at the Iranian Center of Neurological Research, Imam Khomeini Hospital, Tehran, Iran. Additionally, 59 age- and education-matched healthy controls were enrolled (30 for ECAS-B and 29 for ECAS-C). The Montreal Cognitive Assessment (MoCA) was used to validate the ECAS versions.

RESULTS: The Persian versions of ECAS-B and ECAS-C demonstrated strong internal consistency (Cronbach's alpha: 0.88 for ECAS-B and 0.89 for ECAS-C) and a positive correlation with MoCA and ALS-FRS-r scores. The area under the ROC curve was 0.851 for ECAS-B and 0.861 for ECAS-C. ECAS-C scores were significantly lower than ECAS-B scores, suggesting a faster cognitive decline over time. Optimal cutoff values of 72 for ECAS-B and 78 for ECAS-C were identified for detecting cognitive impairment. Cognitive impairment was observed in 10 patients (26.31%) in the ECAS-B group and 15 patients (51.72%) in the ECAS-C group.

CONCLUSIONS: The Persian versions of ECAS-B and ECAS-C demonstrate good validity and reliability for detecting cognitive impairment and tracking cognitive decline in ALS patients.}, } @article {pmid40462117, year = {2025}, author = {Akif, A and Nguyen, TTM and Liu, L and Xu, X and Kulkarni, A and Jiang, J and Zhang, Y and Hao, J}, title = {Targeting NLRP3 signaling with a novel sulfonylurea compound for the treatment of vascular cognitive impairment and dementia.}, journal = {Fluids and barriers of the CNS}, volume = {22}, number = {1}, pages = {55}, pmid = {40462117}, issn = {2045-8118}, support = {R01 NS105787/NS/NINDS NIH HHS/United States ; R21 NS133895/NS/NINDS NIH HHS/United States ; R01NS105787//National Institute of Neurological Disorders and Stroke (NINDS)/ ; R21NS133895-01//National Institute of Neurological Disorders and Stroke (NINDS)/ ; }, mesh = {Animals ; *NLR Family, Pyrin Domain-Containing 3 Protein/antagonists & inhibitors/metabolism/drug effects ; Mice ; *Dementia, Vascular/drug therapy/metabolism ; *Signal Transduction/drug effects ; *Sulfonylurea Compounds/pharmacology ; *Cognitive Dysfunction/drug therapy/metabolism ; Male ; Disease Models, Animal ; Mice, Inbred C57BL ; Carotid Stenosis/complications ; Brain/drug effects/metabolism ; }, abstract = {BACKGROUND: As a key inflammatory factor, the nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 (NLRP3) inflammasome plays a crucial role in neuroinflammation and the progression of neurodegenerative diseases. Dysregulation of NLRP3 signaling can trigger various inflammatory responses in the brain, contributing to the development of neurodegenerative diseases such as ischemic stroke, vascular dementia (VaD), Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). Therefore, the NLRP3 signaling pathway is a promising therapeutic target for the treatment of neurodegenerative diseases, including VaD.

METHODS: In this study, we investigated the therapeutic effects of a synthetic sulfonylurea NLRP3 inhibitor, AMS-17, in a VaD mouse model using bilateral common carotid artery stenosis (BCAS) and elucidated the underlying mechanisms. All mice were randomly divided into three groups: Sham, VaD + Vehicle, and VaD + AMS-17. Cognitive function was assessed using the Y-maze and Morris water maze (MWM) on the 50th day after BCAS. Brain sections and blood serum samples were collected for biomarker analysis and immunohistochemistry. Neurodegeneration, expressions of the molecules involved in the NLRP3 signaling pathways, tight junction proteins, and myelination were assessed using western blotting and immunofluorescence (IF). The levels of Interleukin-1 beta (IL-1β), Tumor Necrosis Factor-alpha (TNF-α) and Interleukin-4 (IL-4) in the blood were measured using ELISA.

RESULTS: AMS-17 treatment improved cognitive function, enhanced blood-brain barrier (BBB) integrity, and promoted remyelination in VaD mice. Additionally, AMS-17 reduced neurodegeneration and decreased the expression of NLRP3 and its associated proteins, Apoptosis-associated speck-like protein (ASC), and cleaved caspase-1 in the brain. It also lowered pro-inflammatory TNF-α and IL-1β levels, while increasing the anti-inflammatory IL-4 level in the blood.

CONCLUSIONS: The findings of this study provide the first promising evidence for the use of AMS-17 in VaD treatment in mice. This study introduces AMS-17 as a novel chemical scaffold with NLRP3 inhibitory activity, which can be further developed for the treatment of VaD in humans.

CLINICAL TRIAL NUMBER: Not applicable.}, } @article {pmid40461666, year = {2025}, author = {Orologio, I and Russo, A and Trojsi, F and Todisco, V and Cirillo, M and Tessitore, A and Silvestro, M}, title = {A case of rapidly progressive juvenile amyotrophic lateral sclerosis associated with a pathogenetic heterozygous de novo variant in the FUS gene.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {}, number = {}, pages = {}, pmid = {40461666}, issn = {1590-3478}, } @article {pmid40460399, year = {2025}, author = {Pommée, T and Bouvier, L and Barnett-Tapia, C and Maffei, MF and Gutz, SE and Tilton-Bolowsky, VE and Martino, R and Berry, JD and Abrahao, A and Zinman, L and Green, JR and Yunusova, Y}, title = {Construct Validity of the Amyotrophic Lateral Sclerosis Bulbar Dysfunction Index-Remote.}, journal = {American journal of speech-language pathology}, volume = {34}, number = {4}, pages = {2189-2211}, pmid = {40460399}, issn = {1558-9110}, support = {F31 DC020108/DC/NIDCD NIH HHS/United States ; R01 DC017291/DC/NIDCD NIH HHS/United States ; T32 DC013017/DC/NIDCD NIH HHS/United States ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/physiopathology/complications ; Male ; Female ; Middle Aged ; Aged ; Reproducibility of Results ; Severity of Illness Index ; Adult ; Disability Evaluation ; Predictive Value of Tests ; Speech Intelligibility ; }, abstract = {PURPOSE: The Amyotrophic Lateral Sclerosis Bulbar Dysfunction Index-Remote (ALSBDI-R) is a clinician-administered tool designed to assess bulbar dysfunction remotely in patients with amyotrophic lateral sclerosis (ALS). This study aimed to evaluate the construct validity of the ALSBDI-R by examining its correlation with established clinical measures and its ability to discriminate among different bulbar disease severities.

METHOD: A total of 92 patients with ALS were recruited from two multidisciplinary clinics. Participants were assessed using the ALSBDI-R, the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R), the Center for Neurologic Study Bulbar Function Scale (CNS-BFS), the Sentence Intelligibility Test, and the Eating Assessment Tool (EAT-10). Construct validity was established through Spearman correlations and comparison of ALSBDI-R scores across bulbar severity groups (asymptomatic, mild, moderate, severe).

RESULTS: Strong correlations were found between ALSBDI-R total scores and bulbar-specific measures such as ALSFRS-R bulbar subscore (r = -.85), CNS-BFS (r = .85), and EAT-10 (r = .77). The ALSBDI-R effectively discriminated between severity groups, supporting its construct validity. Severity bins were created based on median ALSBDI-R total scores for each group.

CONCLUSIONS: The ALSBDI-R is a valid tool for remotely assessing bulbar dysfunction in patients with ALS. Despite several limitations, its ability to capture varying degrees of severity makes it valuable for clinical use and research, offering a standardized approach to monitor disease progression remotely.}, } @article {pmid40460337, year = {2025}, author = {van Unnik, JWJ and Ing, L and Oliveira Santos, M and McDermott, CJ and de Carvalho, M and van Eijk, RPA}, title = {Remote Monitoring of Amyotrophic Lateral Sclerosis Using Digital Health Technologies: Shifting Toward Digitalized Care and Research?.}, journal = {Neurology}, volume = {105}, number = {1}, pages = {e213738}, pmid = {40460337}, issn = {1526-632X}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy/diagnosis ; *Telemedicine ; Wearable Electronic Devices ; Videoconferencing ; Digital Technology ; *Biomedical Technology ; Monitoring, Physiologic/methods ; Digital Health ; }, abstract = {Current care and research pathways for amyotrophic lateral sclerosis (ALS) primarily rely on regularly scheduled visits to specialized centers. These visits provide intermittent clinical information to health care professionals and require patients to travel to the clinic. Digital health technologies enable continuous data collection directly from the patient's home, bringing new opportunities for personalized, timely care and a refined assessment of disease severity in clinical trials. In this review, we summarize the state of the art in digital health technologies for remote monitoring of patients with ALS, ranging from televisits through videoconferencing to sensor-based wearable devices. We explore how these technologies can benefit clinical care and advance treatment development. Despite significant progress, real-world adoption of these technologies remains limited. An overview is provided of the key barriers hindering their widespread implementation and the opportunities to advance the field. Significantly, there is an urgent need for harmonization across stakeholders through consensus guidelines and consortia. These efforts are essential to accelerate progress and harness the full potential of digital health technologies to better meet the needs of patients.}, } @article {pmid40459673, year = {2025}, author = {Dengri, C and Mayberry, W and Koriesh, A and Nouh, A}, title = {Neurology of Androgens and Androgenic Supplements.}, journal = {Current neurology and neuroscience reports}, volume = {25}, number = {1}, pages = {39}, pmid = {40459673}, issn = {1534-6293}, mesh = {Humans ; *Androgens/metabolism/therapeutic use ; *Nervous System Diseases/drug therapy/metabolism ; *Dietary Supplements ; Receptors, Androgen/metabolism ; Animals ; Testosterone/therapeutic use ; }, abstract = {PURPOSE OF REVIEW: This article explores the intricate relationship between androgens, androgen receptors, and the central nervous system. We examine the role of physiologically derived androgens and androgenic supplements in neurodevelopment and neuroplasticity and delve into the involvement of androgen pathways in the pathogenesis of various neurological disorders.

RECENT FINDINGS: This review highlights the increasing recognition of testosterone and androgen signaling in various neurological conditions, with evidence of both protective and harmful effects depending on dosage and context. Although limited to experimental use, testosterone replacement therapy (TRT) may serve potential benefits in the management of multiple sclerosis, epilepsy, headache, Duchenne muscular dystrophy, amyotrophic lateral sclerosis, and Parkinson disease. On the other hand, androgen-blocking treatments may help alter disease progression in spinal and bulbar muscular atrophy. Testosterone supplementation can have potential adverse events when used at a supratherapeutic level, and prenatal testosterone exposure is believed to contribute to the pathogenesis of neurodevelopmental disease. Additionally, androgen-blocking agents could increase the risk of neurodegenerative conditions, such as Parkinson disease and Alzheimer disease. Despite the above findings, there is no established indication of TRT or androgen-blocking medication in neurological disorders. The body of evidence highlighting the involvement of androgens and androgen receptors (ARs) in pathogenesis of neurological diseases is growing. This includes ongoing research exploring the potential therapeutic targets involving the androgen signaling pathway for management of neurological disorders. Future placebo-controlled clinical trials are essential to determine the efficacy and safety of TRT or androgen-blocking therapies in managing neurological disease.}, } @article {pmid40459635, year = {2025}, author = {Abraham, I and Martin, P and Vaghela, S and Klein, T and Chow, E and Rush, M and Morlock, R and Huang, H}, title = {Budget impact analysis of revumenib for the treatment of relapsed or refractory acute leukemias with a KMT2A translocation in the United States.}, journal = {Journal of managed care & specialty pharmacy}, volume = {31}, number = {7}, pages = {680-693}, pmid = {40459635}, issn = {2376-1032}, mesh = {Humans ; United States ; *Myeloid-Lymphoid Leukemia Protein/genetics ; *Histone-Lysine N-Methyltransferase/genetics ; *Leukemia, Myeloid, Acute/drug therapy/economics/genetics ; Budgets ; *Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy/economics/genetics ; Translocation, Genetic ; *Antineoplastic Agents/economics/therapeutic use ; Adult ; Recurrence ; Drug Costs ; Benzamides ; Spiro Compounds ; }, abstract = {BACKGROUND: Acute leukemias (ALs), including acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL), are heterogeneous diseases characterized by different phenotypic, genetic, and molecular alterations that can guide treatment decisions. ALs harboring lysine methyltransferase 2A gene translocation (KMT2t), previously known as mixed-lineage leukemia, are associated with high rates of relapsed or refractory (R/R) disease. Revumenib, a first-in-class oral menin inhibitor, has shown improved clinical outcomes in patients with R/R KMT2At ALs.

OBJECTIVE: To estimate, using a budget impact model (BIM), the financial impact of introducing revumenib for the treatment of adult patients with R/R KMT2At ALs on the formulary of a hypothetical US 1-million-member commercial health plan.

METHODS: The BIM compared scenarios with or without revumenib and the resulting impact on commercial US third-party payers over a 3-year time horizon. Although no other therapies specifically targeted for R/R KMT2At ALs were approved during BIM development, 11 additional pharmacotherapies for R/R ALs (5 for AML and 6 for ALL, not including revumenib) were included as treatment options in the model. Clinical data included adverse event (AE) rates, duration of treatment, time to subsequent treatment, and survival outcomes. Cost inputs (USD 2024) included in the model comprised drug acquisition and administration, grade 3 or greater AEs, treatment-related supportive care and monitoring, subsequent treatment, and end-of-life costs. The differential cost per member per month (PMPM) was estimated. One-way sensitivity analyses varying the costs of drug acquisition and toxicity by ±20% and scenario analyses varying uptake of revumenib and epidemiology inputs, as well as excluding costs related to supportive care and posttreatment discontinuation, were performed.

RESULTS: An estimated 1.7 adult patients (AML, 1.1; ALL, 0.6) were treatment eligible annually. Estimated 3-year total plan costs without and with revumenib were $2,146,564 and $2,126,919, respectively, for savings of -$19,646. Including revumenib was estimated to yield a differential PMPM cost of -$0.0005 over 3 years. The total number of grade 3 or greater AEs was lower over 3 years (10.82 vs 10.99, respectively) in the plan with revumenib vs without. Sensitivity and scenario analyses validated the robustness of the model.

CONCLUSIONS: The BIM demonstrated that including revumenib in a formulary for adult patients with R/R KMT2At ALs was approximately cost neutral, offering patients access to a targeted treatment with potential for improved clinical outcomes.}, } @article {pmid40458045, year = {2025}, author = {Weng, R and Li, X and Yue, H and Xu, Y and Wei, Z and Xu, S and Li, B and Zhang, Z}, title = {A missense mutation in close proximity of ALS-linked PFN1 mutations causes only early-onset Paget's disease of bone.}, journal = {The Journal of clinical endocrinology and metabolism}, volume = {}, number = {}, pages = {}, doi = {10.1210/clinem/dgaf314}, pmid = {40458045}, issn = {1945-7197}, abstract = {CONTEXT: Paget's disease of bone (PDB) is a metabolic disorder characterized by abnormal osteoclast activation. Recently, mutations in the PFN1 gene, which encodes Profilin 1, an actin-binding protein controlling actin dynamics and cell movement, have been linked to early-onset PDB. Interestingly, mutations in PFN1 (C71G, T109M, M114T, E117G, G118V, etc.) are associated with amyotrophic lateral sclerosis (ALS), a neurodegenerative disorder affecting motor neurons.

OBJECTIVE: To provide insights into the underlying molecular mechanism of early-onset PDB.

METHODS: We observed the clinical responses to denosumab in early-onset PDB patients. Additionally, a mouse model carrying the c.335T>C mutation in the Pfn1 gene was generated.

RESULTS: We reported a second Chinese family affected by early-onset PDB with malignant giant cell tumor (GCTs), in which we indentified the same heterozygous missense mutation (c.335T>C/p. L112P) in PFN1 that we have reported previously in another family. Despite its proximity to ALS-linked PFN1 mutations, the PFN1 L112P mutation did not induce ALS in affected individuals. These early-onset PDB patients exhibited a significantly poorer response to denosumab compared to typical PDB patients. The heterozygous mice displayed PDB-like phenotypes, including skeletal deformities and focal osteoclastic lesions with giant osteoclasts, and did not show ALS-like phenotypes. We further show that mutation of Pfn1 leads to enhanced actin ring-like structures at the bone surfaces without affecting NF-κB activation in osteoclast cultures.

CONCLUSION: The observation of recurrent mutations highlights the causative role of PFN1 (L112P) in early-onset PDB/GCT within the Chinese population and provides insights into the physio-pathological functions of Profilin 1.}, } @article {pmid40457777, year = {2025}, author = {Martin, EM and Cichon, C and Choudhury, R and Day, SR and Fatemi, Y and Luther, VP and Stillwell, T and Sung, A}, title = {Society for Healthcare Epidemiology of America (SHEA) infectious diseases fellow infection prevention and control and healthcare epidemiology curriculum.}, journal = {Infection control and hospital epidemiology}, volume = {}, number = {}, pages = {1-10}, doi = {10.1017/ice.2025.85}, pmid = {40457777}, issn = {1559-6834}, abstract = {With the rapid expansion of the Infection Prevention Control/Healthcare Epidemiology (IPC/HE) fields over recent decades, the pivotal roles of IPC/HE in hospital regulation, quality improvement, patient safety, and healthcare finances have become increasingly apparent. Consequently, the demand for effective IPC/HE leaders has surged.[1,2] Training in IPC/HE is essential for all infectious diseases (ID) fellows (both adult and pediatric), including those planning a career in hospital epidemiology as well as those planning to focus on general ID, transplant, HIV, etc. ID fellows, however, have historically felt ill-prepared in IPC/HE. Joiner et al's survey highlighted this gap, revealing that only half of respondents felt adequately trained in infection control, despite half of them participating in infection control in their practice.[3] IPC/HE fellow education is not currently standardized, and most IPC/HE training is led by individual mentors and healthcare facilities.}, } @article {pmid40457619, year = {2025}, author = {Alaydin, HC and Kocak, OK and Arslan, I and Kılınc, H and Boran, HE and Tankisi, H and Cengiz, B}, title = {Assessing MScanFit MUNE in Amyotrophic Lateral Sclerosis: Influence of Nerve Conduction Distance and Temporal Dispersion.}, journal = {Muscle & nerve}, volume = {72}, number = {3}, pages = {408-415}, doi = {10.1002/mus.28446}, pmid = {40457619}, issn = {1097-4598}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology/diagnosis ; Male ; Female ; Middle Aged ; *Neural Conduction/physiology ; *Action Potentials/physiology ; Aged ; Electromyography/methods ; Adult ; Ulnar Nerve/physiopathology ; *Muscle, Skeletal/physiopathology ; Electric Stimulation ; *Motor Neurons/physiology ; }, abstract = {INTRODUCTION/AIMS: MScanFit is a promising method for motor unit number estimation (MUNE) based on compound muscle action potential (CMAP) scanning. Considering that CMAP morphology may be altered by temporal dispersion associated with nerve conduction distance, it is important to evaluate the potential impact of these changes on MScanFit measurements. Therefore, we aimed to investigate the effect of nerve conduction distance on MScanFit MUNE in patients with amyotrophic lateral sclerosis (ALS).

METHODS: MScanFit MUNE was recorded from the abductor digiti minimi (ADM) muscle by stimulating the ulnar nerve at the wrist and elbow in twenty-three ALS patients. Consistency of MScanFit MUNE and size parameters, CMAP amplitude, and CMAP duration were evaluated using intraclass correlation coefficients (ICC).

RESULTS: Significant differences were noted in CMAP amplitudes (6.35 ± 2.5 mV vs. 5.7 ± 2.4 mV; p = 0.003) and CMAP durations (5.8 ± 0.7 ms vs. 6.2 ± 0.8 ms; p < 0.001), reflecting temporal dispersion effects. MUNE values showed high consistency between wrist and elbow stimulations (61 ± 32.4 vs. 61.1 ± 30.7; p = 0.99), with an ICC of 0.86. Similar repeatability was also observed for MScanFit size parameters.

DISCUSSION: The reliability of MScanFit MUNE in determining motor unit values in ALS patients remains consistent regardless of the stimulation distance. Our findings highlight the effectiveness of MScanFit MUNE in evaluating motor unit loss of ALS patients and demonstrate its resilience to temporal dispersion effects. Proximal stimulation serves as a viable alternative, enhancing the utility of MScanFit in clinical settings.}, } @article {pmid40457327, year = {2025}, author = {Gilchrist, L and Mutz, J and Hysi, P and Legido-Quigley, C and Kõks, S and Lewis, CM and Proitsi, P}, title = {Evaluating metabolome-wide causal effects on risk for psychiatric and neurodegenerative disorders.}, journal = {BMC medicine}, volume = {23}, number = {1}, pages = {326}, pmid = {40457327}, issn = {1741-7015}, mesh = {Humans ; *Neurodegenerative Diseases/genetics/metabolism ; Mendelian Randomization Analysis ; *Metabolome ; *Mental Disorders/genetics/metabolism ; Bayes Theorem ; Risk Factors ; }, abstract = {BACKGROUND: Evidence indicates phenotypic and biological overlap between psychiatric and neurodegenerative disorders. Further identification of underlying mutual and unique biological mechanisms may yield novel multi-disorder and disorder-specific therapeutic targets. The metabolome represents an important domain for target identification as metabolites play critical roles in modulating a diverse range of biological processes.

METHODS: We used Mendelian randomisation (MR) to test the causal effects of ~ 1000 plasma metabolites and ~ 300 metabolite ratios on anxiety, bipolar disorder, depression, schizophrenia, amyotrophic lateral sclerosis, Alzheimer's disease, Parkinson's disease and multiple sclerosis. Follow-up analyses were conducted using statistical colocalisation, multivariable Bayesian model averaging MR (MR-BMA) and polygenic risk score analysis in the UK Biobank.

RESULTS: MR analyses identified 85 causal effects involving 77 unique metabolites passing FDR correction and robust sensitivity analyses (IVW-MR OR range 0.73-1.48; pFDR < 0.05). No evidence of reverse causality was identified. Multivariable MR-BMA analyses implicated sphingolipid metabolism in psychiatric disorder risk and carnitine derivatives in risk for amyotrophic lateral sclerosis and multiple sclerosis. Although polygenic risk scores for prioritised metabolites showed limited prediction in the UK Biobank, those nominally significant were directionally consistent with MR estimates. Downstream colocalisation in regions containing influential variants identified greater than suggestive evidence (PP.H4 ≥ 0.6) for a shared causal variant for 29 metabolite/psychiatric disorder trait-pairs on chromosome 11 at the FADS gene cluster. Most of these metabolites were lipids containing linoleic or arachidonic acid. Additional colocalisation was identified between the ratio of histidine-to-glutamine, glutamine, Alzheimer's disease and SPRYD4 gene expression on chromosome 12.

CONCLUSIONS: Although no single metabolite had a causal effect on both a psychiatric and a neurodegenerative disease, results suggest a broad effect of lipids across brain disorders, with a particular role for lipids containing linoleic or arachidonic acid in psychiatric disorders. The metabolites identified here may help inform future targeted interventions.}, } @article {pmid40456951, year = {2025}, author = {Douglas, AGL}, title = {Penetrance and pleiotropy in ATXN2-related amyotrophic lateral sclerosis.}, journal = {European journal of human genetics : EJHG}, volume = {}, number = {}, pages = {}, pmid = {40456951}, issn = {1476-5438}, support = {HMR04192 HM40.01//DH | National Institute for Health Research (NIHR)/ ; }, } @article {pmid40456907, year = {2025}, author = {Rhine, K and Li, R and Kopalle, HM and Rothamel, K and Ge, X and Epstein, E and Mizrahi, O and Madrigal, AA and Her, HL and Gomberg, TA and Hermann, A and Schwartz, JL and Daniels, AJ and Manor, U and Ravits, J and Signer, RAJ and Bennett, EJ and Yeo, GW}, title = {Neuronal aging causes mislocalization of splicing proteins and unchecked cellular stress.}, journal = {Nature neuroscience}, volume = {28}, number = {6}, pages = {1174-1184}, pmid = {40456907}, issn = {1546-1726}, support = {R35 GM148339/GM/NIGMS NIH HHS/United States ; DGE-2038238//National Science Foundation (NSF)/ ; P30-CA014195//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; R01 NS069566/NS/NINDS NIH HHS/United States ; R01-HG004659//U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)/ ; U01 CA267031/CA/NCI NIH HHS/United States ; P30-AG068635//U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ ; 23-PDF-639//Amyotrophic Lateral Sclerosis Association (ALS Association)/ ; P30 AG068635/AG/NIA NIH HHS/United States ; R01 HG004659/HG/NHGRI NIH HHS/United States ; U01-CA267031//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; R35-GM148339//U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)/ ; T32 CA067754/CA/NCI NIH HHS/United States ; R01 NS103172/NS/NINDS NIH HHS/United States ; R01-NS103172//U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; P30 CA014195/CA/NCI NIH HHS/United States ; IL-2023-C2-L4//Target ALS (Target ALS Foundation)/ ; T32-CA067754//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; }, mesh = {Humans ; Animals ; *Neurons/metabolism/pathology ; Mice ; *Aging/metabolism/pathology ; *RNA-Binding Proteins/metabolism ; *Stress, Physiological/physiology ; *Cellular Senescence/physiology ; Cells, Cultured ; DNA-Binding Proteins/metabolism ; Aged ; Fibroblasts/metabolism ; Mice, Inbred C57BL ; }, abstract = {Aging is one of the most prominent risk factors for neurodegeneration, yet the molecular mechanisms underlying the deterioration of old neurons are mostly unknown. To efficiently study neurodegeneration in the context of aging, we transdifferentiated primary human fibroblasts from aged healthy donors directly into neurons, which retained their aging hallmarks, and we verified key findings in aged human and mouse brain tissue. Here we show that aged neurons are broadly depleted of RNA-binding proteins, especially spliceosome components. Intriguingly, splicing proteins-like the dementia- and ALS-associated protein TDP-43-mislocalize to the cytoplasm in aged neurons, which leads to widespread alternative splicing. Cytoplasmic spliceosome components are typically recruited to stress granules, but aged neurons suffer from chronic cellular stress that prevents this sequestration. We link chronic stress to the malfunctioning ubiquitylation machinery, poor HSP90α chaperone activity and the failure to respond to new stress events. Together, our data demonstrate that aging-linked deterioration of RNA biology is a key driver of poor resiliency in aged neurons.}, } @article {pmid40454831, year = {2025}, author = {Santos Silva, C and Pavey, N and Calma, AD and Kiernan, MC and Menon, P and van den Bos, M and Vucic, S}, title = {Utility of Cortical Inhibitory and Facilitatory Neuronal Circuits in Amyotrophic Lateral Sclerosis Diagnosis.}, journal = {European journal of neurology}, volume = {32}, number = {6}, pages = {e70203}, pmid = {40454831}, issn = {1468-1331}, support = {//Motor Neurone Disease Research Institute of Australia/ ; 1024915//National Health and Medical Research Council of Australia/ ; 1055778//National Health and Medical Research Council of Australia/ ; 233//National Health and Medical Research Council of Australia/ ; 510//National Health and Medical Research Council of Australia/ ; GIA 1726//National Health and Medical Research Council of Australia/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/physiopathology ; Male ; Female ; Middle Aged ; Transcranial Magnetic Stimulation/methods ; Cross-Sectional Studies ; Aged ; *Neural Inhibition/physiology ; *Evoked Potentials, Motor/physiology ; Adult ; *Motor Cortex/physiopathology ; }, abstract = {BACKGROUND: Cortical hyperexcitability is an early feature of amyotrophic lateral sclerosis (ALS), linked to dysfunction in inhibitory and facilitatory cortical circuits, measurable using paired-pulse transcranial magnetic stimulation (TMS). Short-interval intracortical inhibition (SICI) is a robust biomarker of inhibitory function and an ALS diagnostic marker. Short interval intracortical facilitation (SICF) serves as a biomarker of facilitatory function, while the index of excitation assesses the contribution of these circuits to hyperexcitability. This study aimed to evaluate the diagnostic effectiveness of SICF and the index of excitation in distinguishing ALS from non-ALS mimic disorders.

METHODS: This cross-sectional study assessed cortical excitability in participants with suspected ALS from two Sydney centres, classified using the Gold Coast criteria. Threshold tracking TMS measured SICI, SICF, and the index of excitation. Diagnostic performance was evaluated using receiver operating characteristic (ROC) analysis, with sensitivity, specificity, and optimal cut-off values determined.

RESULTS: Of 154 participants, 95 were diagnosed with ALS and 48 with non-ALS mimics. SICI demonstrated a marginally higher diagnostic accuracy (AUC 0.84, 95% CI:0.77-0.89) compared to SICF (AUC 0.77, 95% CI:0.68-0.84, p = 0.028). The index of excitation showed comparable accuracy to SICI (AUC 0.82, 95% CI: 0.75-0.88, p = 0.328). The optimal SICF cut-off (≤ -13.6%) provided 70.5% sensitivity and 70.8% specificity, while the index of excitation cut-off (≥ 64.5%) yielded 71.6% sensitivity and 70.8% specificity.

CONCLUSIONS: The present study established modest diagnostic potential of increased SICF and index of excitation in differential ALS from mimic disorders, thereby enhancing understanding of the role of inhibitory and facilitatory cortical circuits in ALS diagnosis.}, } @article {pmid40454605, year = {2025}, author = {Zheng, X and Zhang, K and Zhao, X and Zhou, J and Shen, H and Kong, J and Guo, Y}, title = {Achieving High-Yield Conversion of Janus Transition Metal Dichalcogenides on Diverse Substrates.}, journal = {ACS nano}, volume = {19}, number = {22}, pages = {20744-20752}, doi = {10.1021/acsnano.5c02687}, pmid = {40454605}, issn = {1936-086X}, abstract = {Janus transition metal dichalcogenides (TMDCs) with intrinsic broken mirror symmetry and vertical dipole moment provide an additional degree of freedom to manipulate material symmetry down to atomic-layer thickness. However, despite advances in synthesis strategies, fundamental understanding of this atomic substitution process remains limited, which has impeded their implementation in advanced devices. Here, by using a room-temperature atomic-layer substitution (RT-ALS) strategy, we systematically investigate the critical factors facilitating the high-yield conversion of Janus TMDCs on diverse substrates. Combining Raman spectroscopy probes, X-ray photoelectron spectroscopy (XPS) measurements, and density functional theory (DFT) calculations, we demonstrate that substrates with enhanced electron doping or larger surface polarity substantially benefit the conversion of Janus TMDCs reaching a near-unity yield. Intriguingly, the strong affinity between Janus TMDCs and substrates (e.g., Au) brings about abnormal Raman spectroscopic phenomena. These findings highlight the significance of substrates in achieving the reliable synthesis of Janus two-dimensional materials with improved homogeneity on various substrates. In addition, this takes us one step closer to utilizing Janus TMDCs as a versatile platform in next-generation optoelectronic devices, sensors, and quantum technologies.}, } @article {pmid40454469, year = {2025}, author = {Arnold, FJ and Cui, Y and Michels, S and Colwin, MR and Stockford, CM and Ye, W and Maheswari Jawahar, V and Jansen-West, K and Philippe, J and Gulia, R and Gou, Y and Tam, OH and Menon, S and Situ, WG and Cazarez, SL and Zandi, A and Ehsani, KC and Howard, S and Dickson, DW and Gale Hammell, M and Prudencio, M and Petrucelli, L and Li, W and La Spada, AR}, title = {TDP-43 dysregulation of polyadenylation site selection is a defining feature of RNA misprocessing in amyotrophic lateral sclerosis and frontotemporal dementia.}, journal = {The Journal of clinical investigation}, volume = {135}, number = {11}, pages = {}, pmid = {40454469}, issn = {1558-8238}, support = {R35 NS122140/NS/NINDS NIH HHS/United States ; RF1 NS118570/NS/NINDS NIH HHS/United States ; R01 NS118570/NS/NINDS NIH HHS/United States ; T32 AG000096/AG/NIA NIH HHS/United States ; U54 NS123743/NS/NINDS NIH HHS/United States ; RF1 NS120992/NS/NINDS NIH HHS/United States ; R35 NS097273/NS/NINDS NIH HHS/United States ; R01 CA193466/CA/NCI NIH HHS/United States ; }, mesh = {*Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology ; Humans ; *Frontotemporal Dementia/genetics/metabolism/pathology ; *DNA-Binding Proteins/metabolism/genetics ; *Polyadenylation ; tau Proteins/metabolism/genetics ; }, abstract = {Nuclear clearance and cytoplasmic aggregation of TAR DNA-binding protein 43 (TDP-43) are observed in many neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Although TDP-43 dysregulation of splicing has emerged as a key event in these diseases, TDP-43 can also regulate polyadenylation; yet this has not been adequately studied. Here, we applied the dynamic analysis of polyadenylation from an RNA-Seq (DaPars) tool to ALS/FTD transcriptome datasets and report extensive alternative polyadenylation (APA) upon TDP-43 alteration in ALS/FTD cell models and postmortem ALS/FTD neuronal nuclei. Importantly, many identified APA genes highlight pathways implicated in ALS/FTD pathogenesis. To determine the functional relevance of APA elicited by TDP-43 nuclear depletion, we examined microtubule affinity regulating kinase 3 (MARK3). Nuclear loss of TDP-43 yielded increased expression of MARK3 transcripts with longer 3' UTRs, corresponding with a change in the subcellular distribution of MARK3 and increased neuronal tau S262 phosphorylation. Our findings define changes in polyadenylation site selection as a previously understudied feature of TDP-43-driven disease pathology in ALS/FTD and highlight a potentially important mechanistic link between TDP-43 dysfunction and tau regulation.}, } @article {pmid40453434, year = {2025}, author = {Voosala, S and Sandhya, M and Mathuranath, PS and Mahale, RR}, title = {Autoimmune Encephalitis Pattern on PET-MRI in a Patient with Amyotrophic Lateral Sclerosis.}, journal = {Indian journal of nuclear medicine : IJNM : the official journal of the Society of Nuclear Medicine, India}, volume = {40}, number = {1}, pages = {22-25}, pmid = {40453434}, issn = {0972-3919}, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive primary motor neuron disorder whose etiology is a subject of debate even today. Interplay between multiple genetic and environmental factors and co-existent/antecedent infection, inflammation, and malignancy have all been hypothesized as potentially causative for this disease. Owing to its hybrid diagnostic capability, fluorodeoxyglucose positron emission tomography-magnetic resonance imaging is highly valuable in detecting varied autoimmune encephalitis patterns, one of which we report in a patient with ALS providing insight into autoimmunity as a potential etiology in the pathogenesis of this disease.}, } @article {pmid40453369, year = {2025}, author = {Slagt, C and Van Kuijk, SMJ and Bruhn, J and Van Geffen, GJ and Mommers, L}, title = {First Results of Our Local Practice Guide Used During the Late Phase of Resuscitation in Patients with Refractory VF in Out of Hospital Cardiac Arrest.}, journal = {Open access emergency medicine : OAEM}, volume = {17}, number = {}, pages = {203-213}, pmid = {40453369}, issn = {1179-1500}, abstract = {OBJECTIVE: Treatment of refractory ventricular fibrillation (rVF) is a clinical challenge. If rVF is still present after standard advanced life support (ALS) guideline care, including amiodaron administration, other therapeutic options might be necessary. Based on the available evidence and expertise, our Helicopter Emergency Medical Service (HEMS) team developed a local practice guide for the prolonged resuscitation of patients in rVF and implemented this as standard HEMS care in March 2022.

METHODS: This database study contains all patients treated with our local practice guide during out of hospital cardiac arrest (OHCA) with rVF beyond the fifth regular ALS shock-block. This local practice HEMS treatment algorithm consisted of, among others, cessation of epinephrine and alternating administration of esmolol and norepinephrine combined with enoximone. Data were derived from the HEMS database and the treating hospitals. Primary outcome was the return of spontaneous circulation. Secondary outcome was defined as survival to hospital discharge and cerebral performance. This outcome was compared to the literature to analyze for inferiority of treatment.

RESULTS: In a 21-month period, HEMS was 761 times deployed for OHCA. Nineteen patients were treated with the local practice guide, nine patients (47%) were admitted to hospital with return of spontaneous circulation. Median resuscitation time was 22min. Hospital survival with good neurology was achieved in 42% vs 17% as expected. Exact Clopper-Pearson and logistic regression analysis revealed non-inferiority of the local practice guide. Withholding epinephrine was achieved in 84% of patients. A total of 79% and 90% of patients received esmolol and norepinephrine/enoximone mixture, respectively. Alternative defibrillation positions were indicated in 18 patients but applied in only 6 (33%).

CONCLUSION: In patients with persisting VF despite prolonged advanced life support care, a multifaceted bundle of care approach shows promising results and warrants further research. Alternative drug administrations were found to be substantially easier to achieve compared to alternative defibrillation positions.}, } @article {pmid40452868, year = {2025}, author = {Labarre, A and Guitard, E and Tossing, G and Parker, JA}, title = {har-1/CHCHD10 mutations induce neurodegeneration and mitochondrial fragmentation in Caenorhabditis elegans.}, journal = {microPublication biology}, volume = {2025}, number = {}, pages = {}, pmid = {40452868}, issn = {2578-9430}, abstract = {CHCHD10 encodes a mitochondrial protein that plays a role in cristae morphology and oxidative phosphorylation, with mutations associated with neurodegenerative diseases, including the spectrum of amyotrophic lateral sclerosis and frontotemporal dementia (ALS-FTD). The Caenorhabditis elegans ortholog of CHCHD10 is har-1 , which can be used to model CHCHD10-related neurodegenerative diseases. We focused on two har-1 mutant strains: one featuring a 260 bp deletion (gk3124) and the other with a G73E point mutation (ad2155). Both har-1 mutants displayed progressive paralysis, degeneration of GABAergic motor neurons, and mitochondrial fragmentation. These strains may be valuable tools for investigating pathogenic mechanisms and therapeutic strategies for neurodegenerative diseases.}, } @article {pmid40452867, year = {2025}, author = {Labarre, A and Guitard, E and Tossing, G and Parker, JA}, title = {Suppression of har-1/CHCHD10 phenotypes for ALS-FTD therapy discovery.}, journal = {microPublication biology}, volume = {2025}, number = {}, pages = {}, pmid = {40452867}, issn = {2578-9430}, abstract = {Mutations in CHCHD10 are linked to a variety of neurodegenerative diseases, including amyotrophic lateral sclerosis and frontotemporal dementia (ALS-FTD). The Caenorhabditis elegans orthologue of CHCHD10 is har-1 , and we investigated whether har-1 mutants could be used for therapeutic discovery in ALS-FTD. Our results show that the small molecule pioglitazone and the probiotic Lacticaseibacillus rhamnosus HA-114 can alleviate har-1 mutant phenotypes. These findings suggest that har-1 mutants are suitable for modifier screens and could be adapted for high-throughput drug screening and microbiome studies to aid in discovering therapies for ALS-FTD.}, } @article {pmid40451305, year = {2025}, author = {Cho, SW and Sontam, T and Chen, A and Limmer, EE and Tolkachjov, SN}, title = {Response to Thang et al's "Response to Cho et al's 'GLP-1 receptor agonist use is associated with increased rates of acne vulgaris diagnosis in non-diabetic obese women but not men: A retrospective cohort study'".}, journal = {Journal of the American Academy of Dermatology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jaad.2025.04.085}, pmid = {40451305}, issn = {1097-6787}, } @article {pmid40451302, year = {2025}, author = {Thang, CJ and Garate, D and Sánchez-Feliciano, A and Barbieri, JS}, title = {Response to Cho et al's "GLP-1 receptor agonist use is associated with increased rates of acne vulgaris diagnosis in non-diabetic obese women but not men: A retrospective cohort study".}, journal = {Journal of the American Academy of Dermatology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jaad.2025.03.102}, pmid = {40451302}, issn = {1097-6787}, } @article {pmid40450587, year = {2025}, author = {Mehta, P and Raymond, J and Nair, T and Han, M and Punjani, R and Larson, T and Berry, J and Mohidul, S and Xue, S and Horton, DK}, title = {Incidence of ALS in all 50 states in the United States, data from the National ALS Registry, 2012-2019.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {}, number = {}, pages = {1-9}, doi = {10.1080/21678421.2025.2506448}, pmid = {40450587}, issn = {2167-9223}, abstract = {OBJECTIVE: To summarize amyotrophic lateral sclerosis (ALS) incidence in all 50 states and the District of Columbia from 2012 to 2019. In 2010, the Agency for Toxic Substances and Disease Registry (ATSDR) launched the congressionally mandated National ALS Registry (Registry) to determine the incidence and prevalence of ALS within the United States, characterize demographics, and identify potential risk factors. This is the first analysis of state-level ALS incidence estimates for all 50 states and the District of Columbia.

METHODS: ALS is not a notifiable disease in the United States. As such, the Registry identifies cases using existing national administrative databases (Medicare, Veterans Health Administration, and Veterans Benefits Administration), and a secure web portal that identifies cases not included in the national databases. Confirmed and likely cases are deduplicated and counted as incident cases for the first year they are identified using a validated algorithm. Incident counts, incident rates, and rate ratios were then calculated.

RESULTS: State-level age-adjusted overall incidence rates for 2012 to 2019 ranged from 0.65 per 100,000 persons (Alaska) to 2.25 per 100,000 persons (Vermont), with an overall incidence of 1.44 per 100,000 persons in the United States. New England and the upper Midwest regions had higher incidence rates than national rates.

CONCLUSIONS: These findings summarize the incidence of ALS for all 50 states from 2012 to 2019. This is a continuing effort to identify ALS cases nationally. The establishment of the Registry allows for epidemiological analyses of ALS data and the assessment of potential risk factors.}, } @article {pmid40450581, year = {2025}, author = {Tokuda, E and Leykam, L and Zetterström, P and Brännström, T and Andersen, PM and Marklund, SL}, title = {Diverse effects of coexpression of human SOD1 variants on motor neuron disease.}, journal = {Human molecular genetics}, volume = {}, number = {}, pages = {}, doi = {10.1093/hmg/ddaf088}, pmid = {40450581}, issn = {1460-2083}, support = {56103-7002829//Västerbotten County Council/ ; 223-2808-12//Torsten and Ragnar Söderberg Foundation, Umeå University Insamlingsstiftelsen/ ; 223-1881-13//Torsten and Ragnar Söderberg Foundation, Umeå University Insamlingsstiftelsen/ ; 2.1.12-1605-14//Torsten and Ragnar Söderberg Foundation, Umeå University Insamlingsstiftelsen/ ; 2012.0091//Knut and Alice Wallenberg Foundation/ ; 2014.0305//Knut and Alice Wallenberg Foundation/ ; 2020.0232//Knut and Alice Wallenberg Foundation/ ; 2012-3167//Swedish Research Council/ ; 2017-03100//Swedish Research Council/ ; 2012-0262//Swedish Brain Foundation/ ; 2012-0305//Swedish Brain Foundation/ ; 2013-0279//Swedish Brain Foundation/ ; 2016-0303//Swedish Brain Foundation/ ; 2018-0310//Swedish Brain Foundation/ ; 2020-0353//Swedish Brain Foundation/ ; 2022-0309//Swedish Brain Foundation/ ; }, abstract = {Mutations in superoxide dismutase-1 (SOD1) are a common cause of amyotrophic lateral sclerosis (ALS). Inheritance is as a rule dominant, but in carriers of the most common mutation, D90A, disease can develop in both homozygous and, more rarely, in heterozygous individuals with unexplained differences in clinical presentation. There is mounting evidence that prion-like spread of SOD1 aggregation is the primary cause of the disease. Two different strains of aggregates have been found to arise in human SOD1 (hSOD1) transgenic mouse models of ALS. Strain A is formed by most mutants including hSOD1G85R and hSOD1WT, whereas hSOD1D90A transgenic mice form a distinct strain B in addition to A. To explore the effects of aggregate strain propensities when hSOD1 variants are coexpressed, we generated digenic hSOD1G85R/WT and hSOD1G85R/D90A mice. Coexpression of hSOD1WT considerably shortened the lifespan of hSOD1G85R mice to the extent expected from the neurotoxicities of the variants alone. In contrast, coexpression of hSOD1D90A had a minimal effect on survival, far smaller than expected. Moreover, time from onset to the end stage was markedly prolonged in the hSOD1G85R/D90A mice. Aggregation of hSOD1 developed concomitantly with motor neuron disease, and the aggregates contained large amounts of both coexpressed variants in both digenic models. Our findings suggest that hSOD1WT has high a capacity to coaggregate with mutants and enhance neurotoxicity. Such interactions may be restricted by differences in strain propensities, which may contribute to the primarily recessive inheritance associated with the hSOD1D90A mutation.}, } @article {pmid40449630, year = {2025}, author = {Vu Trung, K and Abou-Ali, E and Gulla, A and Soares, K and Caillol, F and Paik, WH and Napoleon, B and Halimi, A and Masaryk, V and Bruno, MJ and Pérez-Cuadrado-Robles, E and Bolm, L and Seyfried, S and Petrone, MC and Yilmaz, B and Vollmer, C and Berger, A and Maggino, L and Schemmer, P and Wichmann, D and Karam, E and Dugic, A and Kunovsky, L and Regner, S and Gaujoux, S and Hollenbach, M and , }, title = {Development and validation of the SDLD score: a simplified tool to predict successful endoscopic papillectomy in ampullary lesions.}, journal = {Gastrointestinal endoscopy}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.gie.2025.03.1333}, pmid = {40449630}, issn = {1097-6779}, abstract = {BACKGROUND AND AIMS: Endoscopic papillectomy (EP) is the standard treatment for noninvasive ampullary lesions (ALs), whereas advanced cases require surgery. Managing ALs is challenging and may lead to over- or undertreatment. We developed a score to identify the best candidates for endoscopic or surgical treatment.

METHODS: We analyzed 447 patients who underwent EP. The cohort was randomly split into a training set (n = 325) and validation set (n = 122). Logistic regression identified predictors for incomplete resection (R1), which were incorporated into a 4-item score. Performance was assessed using the area under the receiver-operating characteristic curve (AUROC).

RESULTS: Independent predictors for R1 included size ≥30 mm (S), high-grade dysplasia and/or invasive cancer (D), laterally spreading-lesion (L), and bile or pancreatic duct dilation (D), which we named the SDLD score. ALs with 0 to 1 points had the highest complete resection rates (training, 86.0%; validation, 88.5%), whereas ≥2 points significantly increased R1 rates (training, 52.0%; validation, 57.7%; P < .001). The AUROC was 0.792 (training) and 0.708 (validation).

CONCLUSIONS: The SDLD score predicts R1 in EP and aids in treatment decisions.}, } @article {pmid40449058, year = {2025}, author = {Zhang, Q and Ding, Y and Zhang, Y and Li, Q and Shi, S and Liu, Y and Chen, S and Wu, Q and Xu, X and Wu, F and Cheng, X and Niu, Q}, title = {Early cortical alterations and neuropsychological mechanisms in amyotrophic lateral sclerosis.}, journal = {NeuroImage. Clinical}, volume = {47}, number = {}, pages = {103809}, pmid = {40449058}, issn = {2213-1582}, abstract = {OBJECTIVE: This study investigates the characteristics of cortical structural and functional alterations in amyotrophic lateral sclerosis (ALS) patients and their modulation of emotional and cognitive functions, as well as to discuss their diagnostic value in early-stage ALS.

METHODS: Fifty-nine ALS patients (28 in ALS 1 and 31 in ALS 2, categorized using King's College Staging) and 31 healthy controls were evaluated using multiparametric MRI, motor and neuropsychological assessments, and serum neurofilament light chain (NfL) levels. Mediation analyses were performed to examine how cortical alterations influence the relationship between emotional and cognitive functions. Support vector machine (SVM) classification models were constructed to assess the diagnostic utility of differential cortical parameters.

RESULTS: ALS 1 patients exhibited increased cortical thickness (CT) and functional activity in the cingulate and frontotemporal regions, correlating with neuropsychological performance and NfL levels. Mediation analysis revealed that perigenual and frontotemporal functional activity significantly modulated the relationship between depressive symptoms and cognitive function. SVM classification showed that the combined altered regions with Amplitude of Low Frequency Fluctuations (ALFF) model achieved slightly better performance (AUC = 0.853, 95 %CI: 0.687-1.000, p < 0.001) compared to CT (AUC = 0.779, 95 %CI: 0.587-0.972, p < 0.001), although both models showed limited efficacy in differentiating between ALS 1 and ALS 2 groups.

CONCLUSIONS: Cortical structural and functional alterations in ALS mediate the impact of depression on cognitive function, offering insights into the neuropsychological mechanisms of the disease and potential biomarkers for early-stage diagnosis.}, } @article {pmid40446958, year = {2025}, author = {Yuan, L and Yang, Y and Guo, Y and Deng, H}, title = {Genetic architecture of amyotrophic lateral sclerosis: a comprehensive review.}, journal = {Journal of genetics and genomics = Yi chuan xue bao}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jgg.2025.05.008}, pmid = {40446958}, issn = {1673-8527}, abstract = {Amyotrophic lateral sclerosis (ALS), one of the most prevalent neurodegenerative disorders, is pathologically characterized by the progressive degeneration of both upper and lower motor neurons, leading to muscle weakness, paralysis, and death within 2-4 years post-diagnosis. ALS is categorized into familial ALS (FALS) and sporadic ALS, with FALS accounting for approximately 10% of ALS cases. As a genetically heterogeneous disease, ALS exhibits diverse inheritance patterns, including autosomal dominant, autosomal recessive, and X-linked transmission, and genetic factors play pivotal roles in disease pathogenesis. To date, at least 34 disease-causing loci and 32 genes for ALS have been identified. The investigations of mutant protein products and the establishment of animal models have unraveled potential pathogenic pathways, offering insights into the mechanisms of neurodegeneration in ALS. This review focuses on ALS clinical characteristics, neuropathological features, causative loci/genes, genetic susceptibility factors, animal models, and pathogenic mechanisms, with particular attention to recent advances in genetic findings and pathogenic pathways of ALS. Elucidation of the genetic basis of ALS could provide the scientific foundation for personalized treatments to address this recalcitrant disease.}, } @article {pmid40446399, year = {2025}, author = {Holdom, CJ and Pilkar, R and Guo, CC and Eijk, RPAV and Sethi, N and Henderson, RD and Ngo, ST and Steyn, FJ}, title = {Identification of passive wrist-worn accelerometry outcomes for improved disease monitoring and trial design in motor neuron disease.}, journal = {EBioMedicine}, volume = {117}, number = {}, pages = {105779}, pmid = {40446399}, issn = {2352-3964}, mesh = {Humans ; *Accelerometry/methods/instrumentation ; Male ; Female ; Middle Aged ; Aged ; *Wrist ; *Motor Neuron Disease/diagnosis/physiopathology ; Longitudinal Studies ; Disease Progression ; Adult ; Clinical Trials as Topic ; }, abstract = {BACKGROUND: Motor neuron disease (MND) leads to progressive functional decline, making reliable measures of disease progression critical for patient care and clinical trials. Current clinical outcome measures lack the ability to continuously and objectively track functional decline in daily life of patients with MND. This study assessed and validated wrist-worn accelerometry outcome measures for continuous monitoring in MND, with the potential to refine clinical trial outcomes.

METHODS: This longitudinal study included 95 patients with MND who wore an ActiGraph GT9X Link device on their non-dominant wrist for 8 days, with follow-up every 3-4 months. Accelerometer data were processed using ActiLife and GGIR. Joint models were used to simultaneously investigate the longitudinal change in ALS Functional Rating Scale-Revised (ALSFRS-R) scores and accelerometer-derived outcomes alongside their relationship with overall survival. Sample size estimates for clinical trials were generated using both accelerometer- and ALSFRS-R-based outcomes, and principal component analysis (PCA) explored outcome relationships.

FINDINGS: Accelerometer outcomes showed a slower rate of decline (-0.03 to -0.07 SD/month) compared to ALSFRS-R (-0.10 SD/month) and had stronger correlations with ALSFRS-R motor subdomains (partial r: 0.60-0.73). PCA revealed that longitudinal measures of accelerometry were distinct from the ALSFRS-R, highlighting the complementary nature of these measures. Peak 6-min activity predicted smaller clinical trial sample sizes for studies over 12 months. Accelerometer-derived outcomes were not significantly associated with survival.

INTERPRETATION: Wrist-worn accelerometry offers a practical solution for continuous monitoring in MND, complementing ALSFRS-R. Measures of peak performance, and specifically peak 6-min activity shows promise, potentially reducing sample sizes and improving disease tracking over longer duration studies. Further refinement and validation are needed to adopt actigraphy measures as clinical assessment outcomes.

FUNDING: This study was supported by Wesley Medical Research (2016-32), the Honda Foundation, Motor Neurone Disease Research Australia, and FightMND. CJH received a Higher Degree Research Scholarship from UQ. STN received support from the Scott Sullivan Fellowship (MND and Me Foundation/RBWH Foundation), a FightMND Mid-Career Fellowship, and the AIBN.}, } @article {pmid40443243, year = {2025}, author = {Adhya, A and Uppula, S and Raidas, S and Gupta, A and Singh, RK and Vibha, D and Garg, A and Tripathi, M}, title = {Midbrain Atrophy in Mills Syndrome: A Rare Finding Pointing to Diagnosis.}, journal = {The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques}, volume = {}, number = {}, pages = {1-2}, doi = {10.1017/cjn.2025.10135}, pmid = {40443243}, issn = {0317-1671}, } @article {pmid40443183, year = {2025}, author = {Gonçalves, F and Teixeira, MI and Rego, F and Magalhães, B}, title = {The role of spiritual care management - Needs and resources in people with amyotrophic lateral sclerosis: Insights from a mixed-methods study.}, journal = {Palliative & supportive care}, volume = {23}, number = {}, pages = {e111}, doi = {10.1017/S1478951525000495}, pmid = {40443183}, issn = {1478-9523}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/psychology/complications/therapy ; Male ; Female ; Middle Aged ; Aged ; Surveys and Questionnaires ; Qualitative Research ; Adult ; *Spirituality ; Psychometrics/methods/instrumentation ; *Spiritual Therapies/methods/standards ; }, abstract = {OBJECTIVES: To explore the spiritual needs and resources of People with Amyotrophic Lateral Sclerosis (PALS) at different stages of its trajectory and to characterize the experiences of the current state of the disease.

METHODS: A convergent mixed-methods study was conducted using qualitative and quantitative approaches. Participants were assessed using the clinical and sociodemographic data, ALSFRS-R (function assessment), and the GES Questionnaire to evaluate spiritual needs and resources. Data were collected through in-person or online interviews, transcribed and coded. The qualitative analysis was based on the content analysis method. Statistical analysis was performed using SPSS software. Both datasets were integrated during data analysis.

RESULTS: Twenty-four patients were interviewed, with a duration of the illness ranging from 1 year to 12 years. Participants were at different stages of functional dependence. Analyzing the open questions of the GES questionnaire, six categories were established related to the inner world of PALS: Concern, Nuisance, Help, Support, Safety, and Valorization. Contrary to what was hypothesized, no correlations were found between functionality and the spiritual dimensions. Spiritual needs and resources tend to vary with age, with younger ages presenting a more fragile spiritual dimension overall. Also, the intrapersonal and interpersonal dimension seems to play a central role in the lives of PALS. A negative correlation was identified between the feeling of connection to a supreme/transcendent reality and the level of educational qualifications.

SIGNIFICANCE OF RESULTS: Spirituality often provides crucial emotional support, meaning, and resilience during challenging times. Despite its importance, it is often overlooked in clinical settings. The study emphasizes the need for personalized, holistic care, which should include spiritual care support, regardless of the functional state, highlighting the importance of addressing both intrapersonal and interpersonal domains, resources and needs from early phases. Allowing to create a structured care plan that meets patients' individual spiritual needs, that can contribute to a better QoL and reduce suffering.}, } @article {pmid40441800, year = {2025}, author = {Mehmood, N and Riaz, A and Ghuffar, S and Anwaar, S and Jabeen, N and Shaheen, I and Qasim, M and Khan, SS and Rauf, M and Anwar, T and Qureshi, H and Abusalim, GS and Zaman, W and Ansari, MJ and Iqbal, R}, title = {Epidemiology and genetic characterization of Alternaria alternata causing leaf spot in Fragaria × ananassa.}, journal = {Fungal biology}, volume = {129}, number = {4}, pages = {101589}, doi = {10.1016/j.funbio.2025.101589}, pmid = {40441800}, issn = {1878-6146}, mesh = {*Fragaria/microbiology ; *Alternaria/genetics/isolation & purification/classification/pathogenicity ; *Plant Diseases/microbiology ; Phylogeny ; Pakistan/epidemiology ; Incidence ; DNA, Fungal/genetics/chemistry ; Prevalence ; Sequence Analysis, DNA ; Plant Leaves/microbiology ; DNA, Ribosomal Spacer/genetics/chemistry ; }, abstract = {Alternaria leaf spot (ALS), caused by Alternaria alternata, is a major disease threatening strawberry (Fragaria × ananassa) production globally, including in Pakistan. This study investigated the incidence and prevalence of ALS in key strawberry-producing regions of Pakistan and characterized the pathogen using morphological and molecular techniques. Surveys were conducted during the 2014-2015 and 2015-2016 seasons across 182 farms in Punjab, Khyber Pakhtunkhwa, and Islamabad. Disease prevalence was 100% across all regions, with incidence rates ranging from 17.25% in cooler Islamabad to 55% in Mardan, KPK. Pathogenicity tests confirmed A. alternata as the causal agent. Morphological traits and sequencing of the ITS and endoPG genes further validated its identity. Phylogenetic analysis showed close genetic relatedness to known A. alternata isolates. This is the first comprehensive report of ALS in strawberries in Pakistan, confirming A. alternata as the primary pathogen. The widespread occurrence and high incidence highlight the urgent need for effective control measures. Integrated disease management, including resistant cultivars and targeted fungicide use, is strongly recommended. Further research should investigate environmental factors influencing disease spread and severity to support long-term sustainable management of ALS in strawberry cultivation.}, } @article {pmid40441681, year = {2025}, author = {Sarasate, M and Córdoba-Izquierdo, A and Farrero, E and López-Lisbona, R and Díez-Ferrer, M and Trias-Sabrià, P and Plana, M and Povedano, M and Santos, S and Prats, E}, title = {Effect of Noninvasive Ventilation on the Upper Airway in Patients With Amyotrophic Lateral Sclerosis: The Role of Upper-Airway Endoscopy.}, journal = {Respiratory care}, volume = {}, number = {}, pages = {}, doi = {10.1089/respcare.12791}, pmid = {40441681}, issn = {1943-3654}, abstract = {Background: Upper-airway obstruction (UAO) in amyotrophic lateral sclerosis (ALS) may reduce the efficacy of noninvasive ventilation (NIV). NIV can cause or worsen this obstruction, further worsening the disease prognosis. This study aims to describe UAO in ALS patients using upper-airway endoscopy (UA-End) during spontaneous breathing (SB) and NIV and to evaluate the usefulness of UA-End in adjusting NIV parameters to correct any observed obstruction. Methods: This prospective study (2017-2019) involved subjects with ALS and indications for NIV. After optimizing ventilation following standardized procedures, an awake UA-End was performed, first during SB and then during NIV. Endoscopic assessments included identification of the site of UAO using the VOTE classification, assessment of vocal cords, and adjustments of NIV settings to correct any identified obstructions. Afterward, a post hoc analysis was conducted comparing gasometrical and nocturnal oximetry variables between the groups with and without NIV obstruction at 3 and 6 months. Results: In total, 25 subjects were enrolled. UAO was observed in 9 cases (37%) during SB, whereas 12 cases (50%) showed obstruction during NIV, 7 newly appearing. Hypopharyngeal constriction and backward movement of the epiglottis were the most frequent findings. Adjustments in NIV settings during endoscopy improved UAO in all but one case. Survival rates were similar after UA-End adjustments for subjects on NIV, both with and without UAO. Conclusions: This study is, to the best of our knowledge, the first to show the usefulness of UA-End in assessing and correcting UAO in subjects with ALS at NIV initiation. Furthermore, correction of such events through UA-End may have a positive impact on ventilation control and survival.}, } @article {pmid40441157, year = {2025}, author = {Das, T and Zaidi, FK and Farag, M and Ruff, KM and Mahendran, TS and Singh, A and Gui, X and Messing, J and Taylor, JP and Banerjee, PR and Pappu, RV and Mittag, T}, title = {Tunable metastability of condensates reconciles their dual roles in amyloid fibril formation.}, journal = {Molecular cell}, volume = {85}, number = {11}, pages = {2230-2245.e7}, doi = {10.1016/j.molcel.2025.05.011}, pmid = {40441157}, issn = {1097-4164}, support = {R35 NS097974/NS/NINDS NIH HHS/United States ; }, mesh = {Humans ; *Amyloid/metabolism/genetics/chemistry ; *Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology ; Mutation ; *Stress Granules/metabolism/genetics ; *Heterogeneous Nuclear Ribonucleoprotein A1/genetics/metabolism/chemistry ; Protein Domains ; Protein Binding ; }, abstract = {Stress granules form via co-condensation of RNA-binding proteins (RBPs) containing prion-like low-complexity domains (PLCDs) with RNA molecules. Homotypic interactions among PLCDs can drive amyloid fibril formation that is enhanced by amyotrophic lateral sclerosis (ALS)-associated mutations. We report that condensation- versus fibril-driving homotypic interactions are separable for A1-LCD, the PLCD of hnRNPA1. These separable interactions lead to thermodynamically metastable condensates and globally stable fibrils. Interiors of condensates suppress fibril formation, whereas interfaces have the opposite effect. ALS-associated mutations enhance the stability of fibrils and weaken condensate metastability, thus enhancing the rate of fibril formation. We designed mutations to enhance A1-LCD condensate metastability and discovered that stress granule disassembly in cells can be restored even when the designed variants carry ALS-causing mutations. Therefore, fibril formation can be suppressed by condensate interiors that function as sinks. Condensate sink potentials are influenced by their metastability, which is tunable through separable interactions even among minority components of stress granules.}, } @article {pmid40441139, year = {2025}, author = {Workman, MJ and Lim, RG and Wu, J and Frank, A and Ornelas, L and Panther, L and Galvez, E and Perez, D and Meepe, I and Lei, S and Valencia, V and Gomez, E and Liu, C and Moran, R and Pinedo, L and Tsitkov, S and Ho, R and Kaye, JA and , and Thompson, T and Rothstein, JD and Finkbeiner, S and Fraenkel, E and Sareen, D and Thompson, LM and Svendsen, CN}, title = {Large-scale differentiation of iPSC-derived motor neurons from ALS and control subjects.}, journal = {Neuron}, volume = {113}, number = {12}, pages = {2028}, doi = {10.1016/j.neuron.2025.05.022}, pmid = {40441139}, issn = {1097-4199}, } @article {pmid40440345, year = {2025}, author = {Krull, F and Hosseini, S and Bleyer, M and Brenig, B}, title = {Findings from transcriptomics and immunohistochemistry indicate an autoimmune disease targeting brainstem inhibitory interneurons in bovine spastic paresis.}, journal = {PloS one}, volume = {20}, number = {5}, pages = {e0324633}, pmid = {40440345}, issn = {1932-6203}, mesh = {*Paraparesis, Spastic/genetics/immunology/veterinary ; Animals ; Cattle ; *Gene Expression Profiling ; *Immunohistochemistry ; *Autoimmune Diseases/genetics/veterinary ; Interneurons/physiology ; Brain Stem/physiology ; Animal Husbandry/economics/methods/statistics & numerical data ; Dairying/economics/methods/statistics & numerical data ; Pregnancy Proteins/genetics ; Interleukin-21/blood ; Cholecystokinin/genetics/metabolism ; Neuropeptide Y/genetics/metabolism ; Somatostatin/genetics/metabolism ; Shotgun Sequencing ; RNA, Messenger/genetics/metabolism ; Metabolic Networks and Pathways/physiology ; Male ; Female ; }, abstract = {Bovine spastic paresis (BSP) is a progressive neuromuscular disease of unknown origin that causes persistent stiffness of the hind limbs. The symptoms are similar to those of human motor neuron diseases such as primary (PLS) or amyotrophic lateral sclerosis (ALS). BSP occurs worldwide in cattle production with an estimated prevalence of <1%. For Germany, this means that around 20,000 Holstein cattle are affected. BSP is generally considered a hereditary disease, but there is no prevention through breeding programs. As a result, BSP not only affects animal welfare but also leads to economic losses in milk and beef production. Here, we used transcriptomics to analyse the brainstem, spinal cord and affected gastrocnemius muscle tissue of eight animals affected by BSP and eight control animals from slaughterhouses to gain new insights into the molecular mechanisms underlying BSP. We found that the expression of several genes was significantly different in animals affected by BSP compared to control animals. Specific genes for inhibitory neurons were downregulated in the brainstems of the affected animals, namely CCK (cholecystokinin), NPY (neuropeptide Y), and SST (somatostatin). These inhibitory neurotransmitters influence cerebral movement control, among other processes. Furthermore, OOSP2 (oocyte secreted protein 2) was found to be significantly upregulated in the affected animals in all tissues. This expression could best be explained by the presence of T-follicular-helper cells which, through interleukin 21, can trigger a TH-2-dominated immune response and lead to autoimmune encephalitis. Further cases were sampled for confirmation and we detected cell infiltrates of activated microglia and T-cells in the brainstem using immunohistochemistry. Microglial foci were significantly more abundant in animals affected by BSP than control animals. We conclude that BSP is caused by an autoimmune reaction directed against inhibitory interneurons in the brainstem and is due to a combination of genetics and environmental influences. This may result in lost controlling influence on the upper motor neurons via extrapyramidal pathways and therefore triggers the specific symptoms of motor neuron disease.}, } @article {pmid40439916, year = {2025}, author = {Porel, P and Hunjan, G and Kaur, N and Sharma, V and Kaur, M and Mittal, Y and Kaur, R and Aran, KR}, title = {Unlocking the neuroprotective potential of peptide nucleic acids 5 (PNA5) in neurological diseases: molecular mechanisms to therapeutic approaches.}, journal = {Metabolic brain disease}, volume = {40}, number = {5}, pages = {213}, pmid = {40439916}, issn = {1573-7365}, mesh = {Humans ; *Peptide Nucleic Acids/therapeutic use/pharmacology ; Animals ; *Nervous System Diseases/drug therapy/metabolism ; *Neuroprotective Agents/therapeutic use/pharmacology ; Blood-Brain Barrier/drug effects/metabolism ; }, abstract = {Peptide nucleic acids (PNAs) are synthetic nucleic acid analogues offering distinct structural and functional advantages over conventional RNA and DNA, positioning them as powerful molecules in molecular biology. Recently, PNAs have gained significant attention for their potential in the prevention and management of neurological diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), stroke, traumatic brain injury (TBI), spinal cord injury (SCI), depression, and anxiety. PNA5, a specific PNA variant, is highly expressed in neocortical association regions, particularly in primates, and plays a critical role in high-level cognitive functions such as reasoning, decision-making, and problem-solving. It can form stable, sequence-specific hybridizations with nucleic acids, resist nuclease degradation, and efficiently cross cellular membranes, making them ideal candidates for targeting disease-related genes in the brain. PNA5 has shown neuroprotective properties by improving cognitive function, reducing neuroinflammation, and preserving the integrity of the blood-brain barrier (BBB). Additionally, it supports critical processes such as neural migration, axon guidance, and synaptogenesis, which are vital for maintaining proper brain function. This review explores the mechanisms by which PNAs, particularly PNA5, exert therapeutic effects in neurological disorders. It highlights their role in gene modulation, protein regulation, and potential strategies for enhancing PNA delivery to the central nervous system (CNS) and its related disorders.}, } @article {pmid40439808, year = {2025}, author = {Singh, H and Gupta, R and Gupta, M and Ahmad, A}, title = {Aging-induced alterations in microglial cells and their impact on neurodegenerative disorders.}, journal = {Molecular biology reports}, volume = {52}, number = {1}, pages = {515}, pmid = {40439808}, issn = {1573-4978}, mesh = {Humans ; *Microglia/metabolism/pathology ; *Neurodegenerative Diseases/metabolism/pathology ; *Aging/pathology/metabolism ; Animals ; Brain/metabolism/pathology ; Cellular Senescence ; }, abstract = {Senescence causes deterioration in the functioning and physiology of an organism. Microglia, the standing resident immune brain cells transform from neuroprotective to neurotoxic with age. Rapid process motility and cellular migration of microglia in the developing brain, and other characteristics are regarded to be crucial for immunological defense and tissue repair. As they mature, microglia not only differ in their morphology but also in their functioning. However, the exact mechanism related to the atrophies caused by aged microglia or their role in neurodegenerative diseases is still uncertain. The aim of this updated review is to provide insights of how aging microglial cells change and how this influences the development of neurodegenerative diseases. As life expectancy rises, there is an increase in the accumulation of iron, ROS/NOS, protein misfolding and insufficient clearing of debris. This is attributed to the age-dependent alterations in the genes linked to energy metabolism, mitochondrial and lysosome function, and neuroinflammation. Aging microglia often shifts towards a pro-inflammatory state with a reduction of anti-inflammatory cytokines. Aging microglia fail to clear amyloid-beta plaques, accelerates tau-pathology and enhances the chronic neuroinflammation, exacerbating the α-synuclein aggregation. These changes significantly impacted the onset of various neurogenerative disorders such as amyotrophic lateral sclerosis, Parkinson's disease, and Alzheimer's disease etc. However, it is important to note that these microglial aging effects might not be perceived as absolute, due to various limitations such as microglial heterogeneity, intercellular complexity across brain regions and variability in human aging owing to genetic and epigenetic variations. Regardless of this the future perspective of such insights are of immense relevance as novel therapeutic approaches can be formulated if the molecular and cellular mechanisms of aging microglial perturbations are understood. Future research should focus on restoring microglial homeostasis to mitigate the effects of aging on the brain and slowing the progression of neurodegenerative diseases.}, } @article {pmid40438583, year = {2025}, author = {Li, H and Peng, Y and Wu, Y and Chen, Y and Li, J and He, Y and Wang, H and Luo, C and Mo, Z}, title = {Cardiomyocyte-derived exosomes carrying miR-181a-5p facilitate heart-brain crosstalk and exacerbate methamphetamine dependence in rats.}, journal = {Frontiers in pharmacology}, volume = {16}, number = {}, pages = {1541442}, pmid = {40438583}, issn = {1663-9812}, abstract = {BACKGROUND: Methamphetamine (MA) is one of the most harmful synthetic drugs, yet the mechanisms underlying its addiction and relapse remain incompletely understood. This study investigates how cardiomyocyte-derived exosomes carrying miRNAs facilitate heart-brain crosstalk and contribute to MA dependence.

MATERIALS AND METHODS: A conditioned place preference (CPP) model of MA dependence was established in rats. High-throughput sequencing were employed to identify candidate miRNAs in cardiac exosomes and brain tissues. Behavioral assessments, real-time PCR, nanoparticle tracking analysis, in vivo imaging, in vitro uptake assays, network pharmacology, and dual-luciferase reporter assays were used to explore the role of cardiomyocyte-derived exosomes in MA dependence.

RESULTS: MA induced significant CPP in rats. miR-181a-5p was markedly upregulated in cardiac exosomes and brain tissue, with higher levels observed in cardiac exosomes. In vivo biodistribution showed that cardiomyocyte-derived exosomes cross the blood-brain barrier and accumulate in the brain. In vitro uptake assays demonstrated that SH-SY5Y cells internalized these exosomes, leading to increased miR-181a-5p expression. Tail vein injections of miR-181a-5p-enriched exosomes enhanced MA CPP behavior in rats. Network pharmacology revealed 108 potential targets of miR-181a-5p, enriched in processes such as steroid biosynthesis, amide metabolism, and apoptosis, involving pathways related to the endoplasmic reticulum, MAPK signaling, and amyotrophic lateral sclerosis. Molecular docking identified stable interactions between MA and 12 targets, including HSP90B1, TNF, and MAP2K1, with miR-181a-5p binding to the 3'-UTR regions of these targets. Dual-luciferase assays confirmed the negative regulation of six targets by miR-181a-5p.

CONCLUSION: This study reveals that cardiomyocyte-derived exosomes transport miR-181a-5p, facilitating heart-brain crosstalk and exacerbating MA CPP behavior in rats. These effects are mediated through the regulation of key brain targets, including HSP90B1, TNF, and MAP2K1, providing new insights into the molecular mechanisms of MA addiction and potential therapeutic targets.}, } @article {pmid40437235, year = {2025}, author = {Modafferi, S and Farina, S and Esposito, F and Brandi, O and Di Salvio, M and Della Valle, I and D'Uva, S and Scarian, E and Cicio, G and Riccardi, A and Pisati, F and Garbelli, A and Santini, T and Pansarasa, O and Morlando, M and D'Ambrosi, N and Cozzolino, M and Cestra, G and d'Adda di Fagagna, F and Gioia, U and Francia, S}, title = {DNA damage response defects induced by the formation of TDP-43 and mutant FUS cytoplasmic inclusions and their pharmacological rescue.}, journal = {Cell death and differentiation}, volume = {}, number = {}, pages = {}, pmid = {40437235}, issn = {1476-5403}, support = {RIPREI2023_7c8ae10d783c//Istituto Superiore di Sanità (ISS)/ ; PRIN 2020 CXFL4T//Ministero dell'Istruzione, dell'Università e della Ricerca (Ministry of Education, University and Research)/ ; MNESYS (PE0000006)//Ministero dell'Istruzione, dell'Università e della Ricerca (Ministry of Education, University and Research)/ ; CN00000041 CN3 RNA//Ministero dell'Istruzione, dell'Università e della Ricerca (Ministry of Education, University and Research)/ ; PNRR-CN3//Ministero dell'Istruzione, dell'Università e della Ricerca (Ministry of Education, University and Research)/ ; 2021 DDR&ALS//Fondazione Italiana di Ricerca per la Sclerosi Laterale Amiotrofica (Italian Research Foundation for ALS)/ ; 2016 DDRNA&ALS//Fondazione Italiana di Ricerca per la Sclerosi Laterale Amiotrofica (Italian Research Foundation for ALS)/ ; SwitchALS//Fondazione Italiana di Ricerca per la Sclerosi Laterale Amiotrofica (Italian Research Foundation for ALS)/ ; SwitchALS//Fondazione Italiana di Ricerca per la Sclerosi Laterale Amiotrofica (Italian Research Foundation for ALS)/ ; 2021 DDR&ALS//Fondazione Italiana di Ricerca per la Sclerosi Laterale Amiotrofica (Italian Research Foundation for ALS)/ ; 2016 DDRNA&ALS//Fondazione Italiana di Ricerca per la Sclerosi Laterale Amiotrofica (Italian Research Foundation for ALS)/ ; DBA.AD005.225-NUTRAGE-FOE2021//Consiglio Nazionale delle Ricerche (National Research Council)/ ; DBA.AD005.225-NUTRAGE-FOE2021//Consiglio Nazionale delle Ricerche (National Research Council)/ ; Flagship Project Interomics//Consiglio Nazionale delle Ricerche (National Research Council)/ ; TELORNAGING-835103//EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council)/ ; AIRC-IG(21762)//Associazione Italiana per la Ricerca sul Cancro (Italian Association for Cancer Research)/ ; AIRC 5×1000//Associazione Italiana per la Ricerca sul Cancro (Italian Association for Cancer Research)/ ; GGP17111//Fondazione Telethon (Telethon Foundation)/ ; POR FESR 2014-2020//Regione Lombardia (Region of Lombardy)/ ; Ricerca Corrente 2022 - 2024//Ministero della Salute (Ministry of Health, Italy)/ ; Ricerca Corrente 2022 - 2024//Ministero della Salute (Ministry of Health, Italy)/ ; }, abstract = {Formation of cytoplasmic inclusions (CIs) of TDP-43 and FUS, along with DNA damage accumulation, is a hallmark of affected motor neurons in Amyotrophic Lateral Sclerosis (ALS). However, the impact of CIs on DNA damage response (DDR) and repair in this pathology remains unprobed. Here, we show that CIs of TDP-43 and FUS[P525L], co-localizing with stress granules, lead to a dysfunctional DDR activation associated with physical DNA breakage. Inhibition of the activity of the DDR kinase ATM, but not of ATR, abolishes DDR signaling, indicating that DNA double-strand breaks (DSBs) are the primary source of DDR activation. In addition, cells with TDP-43 and FUS[P525L] CIs exhibit reduced DNA damage-induced RNA synthesis at DSBs. We previously showed that the two endoribonucleases DROSHA and DICER, also known to interact with TDP-43 and FUS during small RNA processing, contribute to DDR signaling at DSBs. Treatment with enoxacin, which stimulates DDR and repair by boosting the enzymatic activity of DICER, restores a proficient DDR and reduces DNA damage accumulation in cultured cells with CIs and in vivo in a murine model of ALS. In Drosophila melanogaster, Dicer-2 overexpression rescues TDP-43-mediated retinal degeneration. In summary, our results indicate that the harmful effects caused by TDP-43 and FUS CIs include genotoxic stress and that the pharmacological stimulation of the DNA damage signaling and repair counteracts it.}, } @article {pmid40436457, year = {2025}, author = {Peace, A and White, DA and Hackney, G and Bradburn, M and Norman, P and White, S and Al-Chalabi, A and Baird, W and Beever, D and Cade, J and Coates, E and Cooper, C and Ezaydi, N and Halliday, V and Maguire, C and Shaw, PJ and Stavroulakis, H and Waterhouse, S and Young, TA and McDermott, CJ and , }, title = {Randomised controlled trial with parallel process evaluation and health economic analysis to evaluate a nutritional management intervention, OptiCALS, for patients with amyotrophic lateral sclerosis: study protocol.}, journal = {BMJ open}, volume = {15}, number = {5}, pages = {e096098}, pmid = {40436457}, issn = {2044-6055}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diet therapy/economics ; Cost-Benefit Analysis ; Energy Intake ; Ireland ; Nutrition Therapy/methods ; Quality of Life ; United Kingdom ; Equivalence Trials as Topic ; Multicenter Studies as Topic ; }, abstract = {INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a devastating illness that leads to muscle weakness and death usually within around 3 years of diagnosis. People with ALS (pwALS) often lose weight due to raised energy requirements and symptoms of the disease presenting significant challenges to taking adequate oral diet, with those who lose more weight being at a greater chance of earlier death. There is also some evidence to suggest that a higher calorie diet may benefit the disease course in pwALS, but further research is needed.

METHODS AND ANALYSIS: Two armed, parallel group, superiority, open labelled, randomised controlled trial, with internal pilot, to assess the effectiveness of an early high calorie diet on functional outcomes in ALS, comprising two treatment arms: (1) standard care, (2) standard care with additional active management using the OptiCALS complex intervention to achieve a high calorie diet (initially randomised 1:1, then 1:2 following a protocol amendment). Using a food first approach, pwALS will be encouraged and supported to follow a diet that meets an individualised calorie target from food before prescribing oral nutritional supplements. 259 pwALS will be recruited from up to 20 ALS centres across the United Kingdom and Ireland and followed up for a period of 12 months. Primary outcome is functional change measured over 12 months, using the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale. Secondary end points include measures of functional health, quality of life, calorie intake and weight, as well as time to gastrostomy and survival. A health economic analysis and process evaluation will also be undertaken. Participant recruitment is expected to complete in September 2025, and participant follow-up is expected to complete in September 2026. The results of this study are expected in March 2027.

ETHICS AND DISSEMINATION: The trial was approved by Greater Manchester-North West Research Ethics Committee, reference 20/NW/0334 on 8 September 2020. We will publish the study findings in peer-reviewed academic journals and present at local, national and international conferences where possible.

TRIAL REGISTRATION NUMBER: ISRCTN30588041.}, } @article {pmid40436373, year = {2025}, author = {Vosough, M and Drees, F and Sieber, G and Stach, TL and Beisser, D and Probst, AJ and Boenigk, J and Schmidt, TC}, title = {Integrative Analysis of Nontargeted LC-HRMS and High-Throughput Metabarcoding Data for Aquatic Environmental Studies Using Combined Multivariate Statistical Approaches.}, journal = {Analytical chemistry}, volume = {97}, number = {22}, pages = {11563-11571}, pmid = {40436373}, issn = {1520-6882}, mesh = {Chromatography, Liquid ; Mass Spectrometry ; Multivariate Analysis ; Wastewater/chemistry/analysis ; RNA, Ribosomal, 16S/genetics ; *Water Pollutants, Chemical/analysis ; *High-Throughput Screening Assays ; *DNA Barcoding, Taxonomic ; }, abstract = {Significant progress in high-throughput analytical techniques has paved the way for novel approaches to integrating data sets from different compartments. This study leverages nontarget screening (NTS) via liquid chromatography-high-resolution mass spectrometry (LC-HRMS), a crucial technique for analyzing organic micropollutants and their transformation products, in combination with biological indicators. We propose a combined multivariate data processing framework that integrates LC-HRMS-based NTS data with other high-throughput data sets, exemplified here by 18S V9 rRNA and full-length 16S rRNA gene metabarcoding data sets. The power of data fusion is demonstrated by systematically evaluating the impact of treated wastewater (TWW) over time on an aquatic ecosystem through a controlled mesocosm experiment. Highly compressed NTS data were compiled through the implementation of the region of interest-multivariate curve resolution-alternating least-squares (MCR-ALS) method, known as ROIMCR. By integrating ANOVA-simultaneous component analysis with structural learning and integrative decomposition (SLIDE), the innovative SLIDE-ASCA approach enables the decomposition of global and partial common, as well as distinct variation sources arising from experimental factors and their possible interactions. SLIDE-ASCA results indicate that temporal variability explains a much larger portion of the variance (74.6%) than the treatment effect, with both contributing to global shared space variation (41%). Design structure benefits include enhanced interpretability, improved detection of key features, and a more accurate representation of complex interactions between chemical and biological data. This approach offers a greater understanding of the natural and wastewater-influenced temporal patterns for each data source, as well as reveals associations between chemical and biological markers in an exemplified perturbed aquatic ecosystem.}, } @article {pmid40433509, year = {2025}, author = {Baek, SH and Tae, WS and Park, JW and Kim, BJ}, title = {Assessment of the glymphatic dysfunction in amyotrophic lateral sclerosis using the diffusion tensor imaging along the perivascular spaces index: a pilot study.}, journal = {Frontiers in aging neuroscience}, volume = {17}, number = {}, pages = {1570327}, pmid = {40433509}, issn = {1663-4365}, abstract = {BACKGROUND: The glymphatic system plays a critical role in clearing interstitial waste from the brain. Dysfunction of this system has been linked to various neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). The diffusion tensor imaging-along the perivascular space (DTI-ALPS) index has emerged as a potential neuroimaging biomarker for evaluating glymphatic function. This study investigates whether glymphatic function differs in individuals with ALS compared to those with Parkinson's disease (PD) and normal controls (NCs), using the DTI-ALPS index.

METHODS: This study included 35 ALS patients, 35 age- and sex-matched PD patients, and 13 NCs. Diffusion tensor imaging (DTI) was conducted, and the DTI-ALPS index was calculated. Clinical assessments included demographic data, disease duration, cognitive status, and functional scales. Group comparisons and correlation analyses were performed to assess the relationship between the DTI-ALPS index and clinical parameters.

RESULTS: The ALS group exhibited a significantly lower right-side DTI-ALPS index than the NC group (p = 0.037), while no differences were observed between the ALS and PD groups. The DTI-ALPS index was negatively correlated with age in ALS and PD groups but showed no correlation with clinical measures in the ALS group. Women in the ALS group had a significantly higher DTI-ALPS index than in men.

CONCLUSION: Glymphatic dysfunction may contribute to the pathogenesis of ALS, as evidenced by a reduced DTI-ALPS index compared to NCs. However, its clinical relevance and specificity for ALS remain uncertain. Further studies with larger cohorts are warranted to validate these findings.}, } @article {pmid40432760, year = {2025}, author = {Simkin, RL and Rhymes, ER and Lang, Q and Birsa, N and Sleigh, JN}, title = {Dissection and Whole-Mount Immunofluorescent Staining of Mouse Hind Paw Muscles for Neuromuscular Junction Analysis.}, journal = {Bio-protocol}, volume = {15}, number = {10}, pages = {e5315}, pmid = {40432760}, issn = {2331-8325}, abstract = {The neuromuscular junction (NMJ) is a peripheral synaptic connection between a lower motor neuron and skeletal muscle fibre that enables muscle contraction in response to neuronal stimulation. NMJ dysfunction and morphological abnormalities are commonly observed in neurological conditions, including amyotrophic lateral sclerosis, Charcot-Marie-Tooth disease, and spinal muscular atrophy. Employing precise and reproducible techniques to visualise NMJs in mouse models of neuromuscular disorders is crucial for uncovering aspects of neuropathology, revealing disease mechanisms, and evaluating therapeutic approaches. Here, we present a method for dissecting the deep lumbrical and flexor digitorum brevis (FDB) muscles of the mouse hind paw and describe the process of whole-mount immunofluorescent staining for morphological analysis of NMJs. Similar whole-mount techniques have been applied to other muscles, such as the diaphragm; however, dense connective tissue in adult samples often impedes antibody penetration. Moreover, large hind limb muscles, including the gastrocnemius and tibialis anterior, are commonly used to examine NMJs but require embedding and cryosectioning. These additional steps increase the complexity and duration of the protocol and can introduce sectioning artefacts, including transection of NMJs and disruption of morphology. Using small hind paw muscles enables whole-mounting, which completely eliminates the requirement for embedding and cryosectioning. As a result, the entire neuromuscular innervation pattern can be visualised, allowing a more accurate assessment of NMJ development, denervation, and regeneration in mouse models of neurological disease and nerve injury, which can be applied across all postnatal ages. Key features • Small muscles of the mouse hind paw, i.e., lumbrical and FDB muscles, can be rapidly dissected for whole-mount immunofluorescent analysis without the need for cryosectioning. • This protocol allows visualisation of the entire neuromuscular innervation pattern using axonal (anti-tubulin βIII), pre-synaptic (anti-synaptophysin), and post-synaptic (α-bungarotoxin) markers. • Whole-mount immunofluorescence of hind paw muscles enables assessment of developmental, degenerative, and regenerative phenotypes in young and adult mice across disease and injury models. • High-throughput analysis can be performed using NMJ-Analyser or NMJ-morph to evaluate diverse morphological features of the NMJ.}, } @article {pmid40431734, year = {2025}, author = {Kim, DH and Kim, JH and Jeon, MT and Kim, KS and Kim, DG and Choi, IS}, title = {The Role of TDP-43 in SARS-CoV-2-Related Neurodegenerative Changes.}, journal = {Viruses}, volume = {17}, number = {5}, pages = {}, pmid = {40431734}, issn = {1999-4915}, support = {25-BR-02-03//Korea Brain Research Institute/ ; }, mesh = {Humans ; *DNA-Binding Proteins/metabolism/genetics ; *COVID-19/complications/metabolism/virology/pathology ; *SARS-CoV-2/physiology ; *Neurodegenerative Diseases/metabolism/virology/pathology/etiology ; Virus Replication ; Animals ; }, abstract = {The coronavirus disease 2019 (COVID-19) pandemic has been linked to long-term neurological effects with multifaceted complications of neurodegenerative diseases. Several studies have found that pathological changes in transactive response DNA-binding protein of 43 kDa (TDP-43) are involved in these cases. This review explores the causal interactions between severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and TDP-43 from multiple perspectives. Some viral proteins of SARS-CoV-2 have been shown to induce pathological changes in TDP-43 through its cleavage, aggregation, and mislocalization. SARS-CoV-2 infection can cause liquid-liquid phase separation and stress granule formation, which accelerate the condensation of TDP-43, resulting in host RNA metabolism disruption. TDP-43 has been proposed to interact with SARS-CoV-2 RNA, though its role in viral replication remains to be fully elucidated. This interaction potentially facilitates viral replication, while viral-induced oxidative stress and protease activity accelerate TDP-43 pathology. Evidence from both clinical and experimental studies indicates that SARS-CoV-2 infection may contribute to long-term neurological sequelae, including amyotrophic lateral sclerosis-like and frontotemporal dementia-like features, as well as increased phosphorylated TDP-43 deposition in the central nervous system. Biomarker studies further support the link between TDP-43 dysregulation and neurological complications of long-term effects of COVID-19 (long COVID). In this review, we presented a novel integrative framework of TDP-43 pathology, bridging a gap between SARS-CoV-2 infection and mechanisms of neurodegeneration. These findings underscore the need for further research to clarify the TDP-43-related neurodegeneration underlying SARS-CoV-2 infection and to develop therapeutic strategies aimed at mitigating long-term neurological effects in patients with long COVID.}, } @article {pmid40431070, year = {2025}, author = {Trebol-Aizpurua, E and Eceiza, MV and Jimenez-Martinez, C and Marí, AI and Royuela, M and Zabalza, A and Gil-Monreal, M}, title = {Resistance to Amino Acid Biosynthesis Inhibiting-Herbicides in Amaranthus palmeri Populations from Aragon (Spain).}, journal = {Plants (Basel, Switzerland)}, volume = {14}, number = {10}, pages = {}, pmid = {40431070}, issn = {2223-7747}, support = {2020 117723-RB-I00//Spanish Ministry of Science and Innovation/ ; PhD fellowship//Basque Government/ ; Investigo programme//Public University of Navarre-Government of Navarre/ ; postgraduate research fellowship (call 2024)//Sociedad Española de Malherbología/ ; }, abstract = {Amaranthus palmeri is a highly problematic agricultural weed due to its rapid growth, high seed production, and strong tendency to develop herbicide resistance. In Spain, the initial colonization of A. palmeri began in 2007, when populations were detected at various locations in the province of Lleida (Catalonia). Since then, new infestations have been reported in other regions of the country, primarily infesting maize fields. Although resistance to glyphosate or to acetolactate synthase (ALS) inhibitors has been documented in several populations from Catalonia and Extremadura, little is known about the resistance profile of populations from Aragon. The main objective of this study was to characterize the putative resistance of five populations from Aragon to 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) inhibitors (glyphosate) and ALS inhibitors (nicosulfuron and imazamox). Sensitivity to both mechanisms of action was measured by root growth in vertical plates and shikimate accumulation for glyphosate. Target-site resistance was evaluated by analyzing EPSPS and ALS gene copy numbers and ALS gene mutations. The populations showed high variability, with no multiple resistance detected. The Bujaraloz population showed moderate resistance to glyphosate due to EPSPS gene amplification. In three populations, mutations in the ALS gene conferring resistance were detected. The Trp574Leu mutation was detected in approximately half of the individuals from the Albelda, Tamarite de Litera, and Caspe populations. In the latter, the Pro197Thr mutation was also present. This study reveals significant genetic variability within each population and provides evidence for the spread of herbicide resistance across different regions of Spain.}, } @article {pmid40430989, year = {2025}, author = {Li, Z and Sun, X and Yu, S and Sun, H and Lian, L and Peng, X and Jin, T and Liu, W and Wang, H}, title = {Baseline Sensitivity of Echinochloa crus-galli (L.) P.Beauv. and Leptochloa chinensis (L.) Nees to Flusulfinam, a New 4-Hydroxyphenylpyruvate Dioxygenase (HPPD)-Inhibiting Herbicide in Rice, in China.}, journal = {Plants (Basel, Switzerland)}, volume = {14}, number = {10}, pages = {}, pmid = {40430989}, issn = {2223-7747}, support = {ZR2024QC067//Shandong Provincial Natural Science Foundation/ ; 32202353//National Natural Science Foundation of China/ ; 2021CXGC010811//Key R&D Program of Shandong Province, China/ ; 2023YFD1400501//National Key R&D Program of China/ ; }, abstract = {Flusulfinam is a 4-hydroxyphenylpyruvate dioxygenase (HPPD)-inhibiting herbicide applied post-emergence (POST) to control Echinochloa crus-galli (L.) P.Beauv., Leptochloa chinensis (L.) Nees, Digitaria sanguinalis (Linn.) Scop. and other annual weeds in directly seeded and transplanted paddy fields in China, registered in September 2024. Notably, compared with other HPPD inhibitors in rice, flusulfinam exhibits consistently high safety in both japonica and indica rice varieties. Meanwhile, flusulfinam has no target-site cross-resistance with traditional acetolactate synthase (ALS)-inhibiting, acetyl-CoA carboxylase (ACCase)-inhibiting, and auxin herbicides. Moreover, as the only heterocyclic-amide-structured herbicide in the HPPD inhibitors, it poses a low risk of metabolic cross-resistance with the other HPPD inhibitors, making it a promising candidate for managing herbicide-resistant weeds in rice fields. In this study, the baseline sensitivity to flusulfinam of E. crus-galli and L. chinensis in paddy fields in China was established using dose-response assays between June and October 2023. Thirty-nine populations of E. crus-galli and forty-three populations of L. chinensis, collected from rice fields across various major rice-producing regions in China, exhibited susceptibility to flusulfinam. The GR50 values ranged from 0.15 to 19.39 g active ingredient (a.i.) ha[-1] for E. crus-galli and from 7.82 to 49.92 g a.i. ha[-1] for L. chinensis, respectively, far below the field recommended rate of flusulfinam. Meanwhile, the GR50 values of E. crus-galli and L. chinensis to flusulfinam were both distributed as a unimodal curve, with baseline sensitivity (GR50b) of 6.48 g a.i. ha[-1] and 22.38 g a.i. ha[-1], respectively. The SI50 value showed 129.27-fold and 6.38-fold variability in flusulfinam sensitivity among the 39 E. crus-galli field populations and 43 L. chinensis filed populations, while the variability declined to 2.99-fold and 2.23-fold when the SI50b value was used. This study substantiated the efficacy of flusulfinam against E. crus-galli and L. chinensis in Chinese paddy fields and furnished a benchmark for monitoring temporal variations in the susceptibility of field populations of E. crus-galli and L. chinensis to flusulfinam.}, } @article {pmid40429802, year = {2025}, author = {Carnaroli, M and Deriu, MA and Tuszynski, JA}, title = {Computational Search for Inhibitors of SOD1 Mutant Infectivity as Potential Therapeutics for ALS Disease.}, journal = {International journal of molecular sciences}, volume = {26}, number = {10}, pages = {}, pmid = {40429802}, issn = {1422-0067}, mesh = {*Superoxide Dismutase-1/genetics/chemistry/antagonists & inhibitors/metabolism ; *Amyotrophic Lateral Sclerosis/genetics/drug therapy ; Humans ; Molecular Docking Simulation ; Molecular Dynamics Simulation ; *Mutation ; Protein Multimerization ; }, abstract = {Familial amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by the selective degeneration of motor neurons. Among the main genetic causes of ALS, over 200 mutations have been identified in the Cu/Zn superoxide dismutase (SOD1) protein, a dimeric metalloenzyme essential for converting superoxides from cellular respiration into less toxic products. Point mutations in SOD1 monomers can induce protein misfolding, which spreads to wild-type monomers through a prion-like mechanism, leading to dysfunctions that contribute to the development of the disease. Understanding the structural and functional differences between the wild-type protein and its mutated variants, as well as developing drugs capable of inhibiting the propagation of misfolding, is crucial for identifying new therapeutic strategies. In this work, seven SOD1 mutations (A4V, G41D, G41S, D76V, G85R, G93A, and I104F) were selected, and three-dimensional models of SOD1 dimers composed of one wild-type monomer and one mutated monomer were generated, along with a control dimer consisting solely of wild-type monomers. Molecular dynamics simulations were conducted to investigate conformational differences between the dimers. Additionally, molecular docking was performed using a library of ligands to identify compounds with high affinity for the mutated dimers. The study reveals some differences in the mutated dimers following molecular dynamics simulations and in the docking of the selected ligands with the various dimers.}, } @article {pmid40429767, year = {2025}, author = {Bokulic Panichi, L and Stanca, S and Dolciotti, C and Bongioanni, P}, title = {The Role of Oligodendrocytes in Neurodegenerative Diseases: Unwrapping the Layers.}, journal = {International journal of molecular sciences}, volume = {26}, number = {10}, pages = {}, pmid = {40429767}, issn = {1422-0067}, mesh = {Humans ; *Oligodendroglia/metabolism/pathology ; *Neurodegenerative Diseases/pathology/metabolism/etiology ; Animals ; Myelin Sheath/metabolism/pathology ; }, abstract = {Neurodegenerative diseases (NDs), including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis/motor neuron disease, and multiple sclerosis, are characterized by progressive loss of neuronal structure and function, leading to severe cognitive, motor, and behavioral impairments. They pose a significant and growing challenge due to their rising prevalence and impact on global health systems. The societal and emotional toll on patients, caregivers, and healthcare infrastructures is considerable. While significant progress has been made in elucidating the pathological hallmarks of these disorders, the underlying cellular and molecular mechanisms remain incompletely understood. Increasing evidence implicates oligodendrocytes and their progenitors-oligodendrocyte progenitor cells (OPCs)-in the pathogenesis of several NDs, beyond their traditionally recognized role in demyelinating conditions such as MS. Oligodendrocytes are essential for axonal myelination, metabolic support, and neural circuit modulation in the central nervous system. Disruptions in oligodendrocyte function and myelin integrity-manifesting as demyelination, hypomyelination, or dysmyelination-have been associated with disease progression in various neurodegenerative contexts. This review consolidates recent findings on the role of OPCs in NDs, explores the concept of myelin plasticity, and discusses therapeutic strategies targeting oligodendrocyte dysfunction. By highlighting emerging research in oligodendrocyte biology, this review aims to provide a short overview of its relevance to neurodegenerative disease progression and potential therapeutic advances.}, } @article {pmid40429496, year = {2025}, author = {Watt, NA and Hockley, N and Armitage, JA}, title = {Exploring the Risk: Peripheral Retinal Degenerations in Young Australian Adults.}, journal = {Journal of clinical medicine}, volume = {14}, number = {10}, pages = {}, pmid = {40429496}, issn = {2077-0383}, abstract = {Background/Objectives: Peripheral retinal degenerations (PRDs) are structural anomalies in the outer regions of the retina, typically emerging in adolescence and early adulthood. Early detection is crucial, as some PRDs can lead to sight-threatening complications, such as retinal detachment, if left unmanaged. Due to a paucity of research regarding PRDs and their association with axial length (AL) and refractive error (RE) in young Australian adults, this study aimed to investigate the prevalence of PRDs in this population and establish whether AL and RE could help predict the likelihood of PRD occurrence. Methods: A cross-sectional study was conducted on a mixed population (n = 221) of Australian adults aged 18 to 40. Demographic data, RE, AL, and a series of ultra-widefield (UWF) retinal images were obtained from participants' undilated eyes using the Zeiss Clarus[TM] 500. Results: The overall PRD prevalence was 8.15% (n = 442 eyes). Binary logistic regression revealed that a longer AL was a more significant factor in increasing the risk of PRD development across all myopia classifications compared to emmetropia than RE. The likelihood of a PRD was 50% at an AL of 26.9 mm and -6.50D of myopia, and 95% at 29.6 mm and -11.00D. Conclusions: PRD prevalence was lower than reported in other global studies, perhaps reflecting the diverse ethnic makeup of the cohort. While our study supports the conventional understanding that longer ALs, and high myopia are key risk factors for developing a PRD, it also provides new insights into the likelihood of detecting a PRD at a given AL or RE in a mixed population. This information is crucial for eye care practitioners, enabling early identification of at-risk individuals and screening for PRDs that may increase the risk of retinal detachment.}, } @article {pmid40428860, year = {2025}, author = {Laucius, O and Drūteika, J and Vanagas, T and Balnytė, R and Radžiūnas, A and Vaitkus, A}, title = {Ultrasonography of the Vagus Nerve for ALS Patients: Correlations with Clinical Data and Dysfunction of the Autonomic Nervous System.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {61}, number = {5}, pages = {}, pmid = {40428860}, issn = {1648-9144}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology/complications/diagnostic imaging ; Male ; Female ; *Vagus Nerve/diagnostic imaging/physiopathology ; Middle Aged ; Aged ; Ultrasonography/methods ; *Autonomic Nervous System/physiopathology ; Prospective Studies ; Cohort Studies ; }, abstract = {Background and Objectives: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder characterized by the degeneration of both upper and lower motor neurons, leading to the rapid decline of motor function. In recent years, dysfunction of the autonomic nervous system (ANS) has also been increasingly recognized as a contributing factor in various neurodegenerative diseases, including ALS. This study is the second publication from our ALS research cohort at Kaunas Clinics. Our previous work examined ultrasonographic changes in the phrenic nerve as a supplementary diagnostic approach for ALS. Materials and Methods: In the present study, we investigated ultrasonographic alterations of the vagus nerve within the same ALS cohort, aiming to explore correlations with ANS involvement. We performed high-resolution ultrasonography of the vagus nerve (VN), collected clinical data, conducted heart rate monitoring, and evaluated respiratory function. Results: We prospectively included 32 ALS patients meeting "Gold Coast" criteria and 64 age- and sex-matched control patients. The average onset of ALS was 57.97 ± 9.22 years, and the duration of the disease was15.41 ± 9.04 months. For ALS patients, we found significantly reduced vagus nerve cross-sectional area (CSA) at the level of the carotid artery bifurcation bilaterally compared to controls (right VN 1.86 ± 0.21 vs. 2.07 ± 0.18 mm[2], p < 0.001; left VN 1.69 ± 0.21 vs. 1.87 ± 0.21 mm[2], p < 0.001). Reduced values of the left VN positively correlated with the reduced values of FEV1% and sO2. Conclusions: Our findings revealed a significant bilateral reduction in vagus nerve size in ALS patients compared to controls, suggesting that vagal atrophy may serve as a potential marker of autonomic dysfunction in ALS.}, } @article {pmid40428407, year = {2025}, author = {Škarica, M and Acsadi, G and Živković, SA}, title = {Pontocerebellar Hypoplasia Type 1 and Associated Neuronopathies.}, journal = {Genes}, volume = {16}, number = {5}, pages = {}, pmid = {40428407}, issn = {2073-4425}, mesh = {Humans ; *Olivopontocerebellar Atrophies/genetics/pathology ; *Cerebellar Diseases/genetics/pathology ; }, abstract = {Pontocerebellar hypoplasia is a rare neurodegenerative syndrome characterized by severe hypoplasia or atrophy of pons and cerebellum that may be associated with other brain malformations, microcephaly, optic nerve atrophy, dystonia, ataxia and neuromuscular disorders. At this time, there are 17 variants of PCH distinguished by clinical presentation and distinctive radiological and biochemical features in addition to pontine and cerebellar hypoplasia. PCH1 is defined as PCH variant associated with anterior horn degeneration in the spinal cord with muscle weakness and hypotonia, and is associated with recessive variants in genes VRK1, EXOSC3, EXOSC8, EXOSC9 and SLC25A46. Neuromuscular manifestations may clinically present as amyotrophic lateral sclerosis (ALS), motor neuropathy (HMN) or neuronopathy (non-5q spinal muscular atrophy; SMA) or sensorimotor polyneuropathy (HMSN). Physiologic functions of PCH1-associated genes include regulation of RNA metabolism, mitochondrial fission and neuronal migration. Overall, complex phenotypes associated with PCH1 gene variants ranging from PCH and related neurodevelopmental disorders combined with neuromuscular disorders to isolated neuromuscular disorders have variable outcomes with isolated neuromuscular disorders typically having later onset with better outcomes. Improved understanding of pathogenesis of pontocerebellar hypoplasia and its association with motor neuronopathies and peripheral neuropathies may provide us with valuable insights and lead to potential new therapeutic targets for neurodegenerative disorders.}, } @article {pmid40428327, year = {2025}, author = {Papapanagiotou, AP and Alvanou, MV and Giantsis, IA and Vasilakoglou, I and Eleftherohorinos, IG}, title = {Characterization of the Giant Foxtail's (Setaria faberi) ALS Gene and Its Enhanced Metabolism-Based Cross-Resistance to Nicosulfuron and Rimsulfuron.}, journal = {Genes}, volume = {16}, number = {5}, pages = {}, pmid = {40428327}, issn = {2073-4425}, mesh = {*Acetolactate Synthase/genetics/metabolism/antagonists & inhibitors ; *Sulfonylurea Compounds/pharmacology ; *Herbicide Resistance/genetics ; *Pyridines/pharmacology ; Herbicides/pharmacology ; *Setaria Plant/genetics/drug effects/enzymology ; *Plant Proteins/genetics/metabolism ; Zea mays/genetics/drug effects ; }, abstract = {BACKGROUND: Weed herbicide resistance is a serious problem in crop protection globally. Giant foxtail (Setaria faberi R.A.N. Herrm.) populations cannot be controlled by acetolactate synthase (ALS)-inhibiting herbicides in a few corn (Zea mays L.) monoculture fields.

METHODS: Five putative resistant giant foxtail populations, originating from corn monoculture fields in northeastern Greece, were evaluated for possible evolution of ALS-inhibitor resistance (nicosulfuron, rimsulfuron). The resistance ratio, the underlying resistance mechanism, and its impact on competitive ability against corn were studied.

RESULTS: The whole-plant rate-response assays showed that these populations were resistant (R) to the sulfonylureas nicosulfuron and rimsulfuron, but susceptible (S) to imidazolinone imazamox, triketone 4-hydroxyphenylpyruvate dioxygenase inhibitor tembotrione, and acetyl-CoA carboxylase inhibitor cycloxydim. The sequencing of the ALS gene did not reveal the presence of resistance-associated point mutations, indicating that the resistance was probably not target-site mediated. This was confirmed by the application of piperonyl butoxide two hours before nicosulfuron application, which reversed the resistance in all R giant foxtail populations, supporting the evidence of enhanced metabolism-mediated resistance. The competition study between corn and R or S giant foxtail populations indicated no stable trend reduction in corn traits, suggesting that the resistance mechanism was not associated with the competitive ability of the R populations. The novel ALS genotype in S. faberi, characterized for the first time and submitted to the GenBank database with accession number PV016837, indicated a closer genetic relationship with the S. viridis ALS gene than with S. italica.

CONCLUSIONS: Five giant foxtail populations have evolved metabolism-based resistance to the ALS-inhibiting herbicides nicosulfuron and rimsulfuron.}, } @article {pmid40428092, year = {2025}, author = {Vaccarino, F and Quattrocchi, CC and Parillo, M}, title = {Susceptibility-Weighted Imaging (SWI): Technical Aspects and Applications in Brain MRI for Neurodegenerative Disorders.}, journal = {Bioengineering (Basel, Switzerland)}, volume = {12}, number = {5}, pages = {}, pmid = {40428092}, issn = {2306-5354}, abstract = {Susceptibility-weighted imaging (SWI) is a magnetic resonance imaging (MRI) sequence sensitive to substances that alter the local magnetic field, such as calcium and iron, allowing phase information to distinguish between them. SWI is a 3D gradient-echo sequence with high spatial resolution that leverages both phase and magnitude effects. The interaction of paramagnetic (such as hemosiderin and deoxyhemoglobin), diamagnetic (including calcifications and minerals), and ferromagnetic substances with the local magnetic field distorts it, leading to signal changes. Neurodegenerative diseases are typically characterized by the progressive loss of neurons and their supporting cells within the neurovascular unit. This cellular decline is associated with a corresponding deterioration of both cognitive and motor abilities. Many neurodegenerative disorders are associated with increased iron accumulation or microhemorrhages in various brain regions, making SWI a valuable diagnostic tool in clinical practice. Suggestive SWI findings are known in Parkinson's disease, Lewy body dementia, atypical parkinsonian syndromes, multiple sclerosis, cerebral amyloid angiopathy, amyotrophic lateral sclerosis, hereditary ataxias, Huntington's disease, neurodegeneration with brain iron accumulation, and chronic traumatic encephalopathy. This review will assist radiologists in understanding the technical framework of SWI sequences for a correct interpretation of currently established MRI findings and for its potential future clinical applications.}, } @article {pmid40427878, year = {2025}, author = {Batterman, SA and Islam, MK and Jang, DG and Feldman, EL and Goutman, SA}, title = {Life Course Exposure to Cyanobacteria and Amyotrophic Lateral Sclerosis Survival.}, journal = {International journal of environmental research and public health}, volume = {22}, number = {5}, pages = {}, pmid = {40427878}, issn = {1660-4601}, support = {1R01NS127188-04D4/NH/NIH HHS/United States ; 1K23ES027221-02D2/NH/NIH HHS/United States ; 3P30ES017885-03D3/NH/NIH HHS/United States ; 1R01ES030049-03A3/NH/NIH HHS/United States ; (no number)//Scott L. Pranger ALS Clinic Fund/ ; (no number)//NeuroNetwork for Emerging Therapies/ ; (no number)//Andrea and Lawrence Wolfe Brain Health Initiative/ ; (no number)//Robert and Katherine Jacobs Environmental Health Initiative Fund/ ; (no number)//Coleman Therapeutic Discovery Fund/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/mortality/epidemiology ; Humans ; *Cyanobacteria ; *Environmental Exposure ; *Microcystins/toxicity ; Middle Aged ; *Harmful Algal Bloom ; Female ; Male ; Aged ; Adult ; }, abstract = {Cyanobacterial harmful algal blooms (cyanoHABs) occur worldwide and can cause ingestion and inhalation exposure to microcystin and other potent toxins. This study develops life course exposure measures for cyanobacteria for application in population studies and then associates these measures with the survival of individuals with amyotrophic lateral sclerosis (ALS). The exposure measures utilize an individual's residence history, date of disease onset, and satellite data from the Cyanobacteria Assessment Network. Residence duration for selected exposure windows referenced to disease onset date was used to weight cyanobacteria concentrations in water bodies within 0.25 to 10 km of each residence. Different concentration metrics, buffer sizes, and exposure windows were evaluated. The 2.5 and 5 km buffers best balanced the likelihood and plausibility of exposure while still resolving exposure contrasts. Over their lifetime, most study participants lived within 5 km of cyanobacteria blooms, and the exposure was associated with up to 0.89 years shorter survival, with significant interactions for individuals reporting swimming, fishing, and private wells. Our findings suggest a new and modifiable risk factor for ALS survival, and a need to confirm exposures and epidemiological findings. These cyanoHAB exposure estimates can facilitate population studies that can discover new relationships with neurodegenerative and other diseases.}, } @article {pmid40427436, year = {2025}, author = {Minuti, A and Raffaele, I and Scuruchi, M and Lui, M and Muscarà, C and Calabrò, M}, title = {Role and Functions of Irisin: A Perspective on Recent Developments and Neurodegenerative Diseases.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {14}, number = {5}, pages = {}, pmid = {40427436}, issn = {2076-3921}, support = {Current Research Funds 2025 (RRC-2025-23686388)//Ministero della Salute/ ; }, abstract = {Irisin is a peptide derived from fibronectin type III domain-containing protein 5 (FNDC5) and is primarily produced by muscle fibers under the regulation of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) during exercise. Irisin has been the subject of extensive research due to its potential as a metabolic regulator and its antioxidant properties. Notably, it has been associated with protective actions within the brain. Despite growing interest, many questions remain regarding the molecular mechanisms underlying its effects. This review summarizes recent findings on irisin, highlighting its pleiotropic functions and the biological processes and molecular cascades involved in its action, with a particular focus on the central nervous system. Irisin plays a crucial role in neuron survival, differentiation, growth, and development, while also promoting mitochondrial homeostasis, regulating apoptosis, and facilitating autophagy-processes essential for normal neuronal function. Emerging evidence suggests that irisin may improve conditions associated with non-communicable neurological diseases, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, frontotemporal dementia, and multiple sclerosis. Given its diverse benefits, irisin holds promise as a novel therapeutic agent for preventing and treating neurological diseases.}, } @article {pmid40426973, year = {2025}, author = {Ivantsik, O and Exarchos, TP and Vrahatis, AG and Vlamos, P and Krokidis, MG}, title = {Exploring Protein Misfolding in Amyotrophic Lateral Sclerosis: Structural and Functional Insights.}, journal = {Biomedicines}, volume = {13}, number = {5}, pages = {}, pmid = {40426973}, issn = {2227-9059}, support = {TAEDR-0535850.//This work was partially supported by the European Union-Next Generation EU, Greece 2.0 Na-tional Recovery and Resilience Plan Flagship program TAEDR-0535850./ ; }, abstract = {Protein functionality depends on its proper folding, making protein misfolding crucial for the function of proteins and, by extension, cells and the whole organism. Increasing evidence supports the role of protein misfolding in the pathogenesis of neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS). ALS is a rapidly progressive disease diagnosed at a prevalence of 5 cases per 100,000, with approximately 2-3 patients per 100,000 diagnosed each year. To date, there is no cure, and the disease usually leads to death within 2 to 5 years from diagnosis. There are two types of the disorder: familial ALS (fALS), accounting for approximately 10% of cases, and sporadic (sALS), accounting for the remaining 90%. The hallmark of ALS, regardless of type, is the protein aggregates found in patients' tissues. This suggests that the disruption of proteostasis plays a critical role in the development of the disease. Herein, we stress the distinct factors that lead to protein misfolding and aggregate formation in ALS. Specifically, we highlight several triggering factors affecting protein misfolding, namely mutations, errors in the processes of protein production and trafficking, and failures of folding and chaperone machinery. Gaining a deeper understanding of protein aggregation will improve our comprehension of disease pathogenesis and potentially uncover new therapeutic approaches.}, } @article {pmid40426848, year = {2025}, author = {Spargo, TP and Iacoangeli, A and Ryten, M and Forzano, F and Pearce, N and Al-Chalabi, A}, title = {Modelling Population Genetic Screening in Rare Neurodegenerative Diseases.}, journal = {Biomedicines}, volume = {13}, number = {5}, pages = {}, pmid = {40426848}, issn = {2227-9059}, abstract = {Importance: Genomic sequencing enables the rapid identification of a breadth of genetic variants. For clinical purposes, sequencing for small genetic variations is considered a solved problem, while challenges remain for structural variants, given the lower sensitivity and specificity. Interest has recently risen among governing bodies in developing protocols for population-wide genetic screening. However, usefulness is constrained when the probability of being affected by a rare disease remains low, despite a positive genetic test. This is a common scenario in neurodegenerative disorders. The problem is recognised among statisticians and statistical geneticists but is less well-understood by clinicians and researchers who will act on these results, and by the general public who might access screening services directly without the appropriate support for interpretation. Observations: We explore the probability of subsequent disease following genetic screening of several variants, both single nucleotide variants (SNVs) and larger repeat expansions, for two neurological conditions, Huntington's disease (HD) and amyotrophic lateral sclerosis (ALS), comparing these results with screening for phenylketonuria, which is well-established. The risk following a positive screening test was 0.5% for C9orf72 in ALS and 0.4% for HTT in HD when testing repeat expansions, for which the test had sub-optimal performance (sensitivity = 99% and specificity = 90%), and 12.7% for phenylketonuria and 10.9% for ALS SOD1 when testing pathogenic SNVs (sensitivity = 99.96% and specificity = 99.95%). Subsequent screening confirmation via PCR for C9orf72 led to a 2% risk of developing ALS as a result of the reduced penetrance (44%). Conclusions and Relevance: We show that risk following a positive screening test result can be strikingly low for rare neurological diseases, even for fully penetrant variants such as HTT, if the test has sub-optimal performance. Accordingly, to maximise the utility of screening, it is vital to prioritise protocols with very high sensitivity and specificity, and a careful selection of markers for screening, giving regard to clinical interpretability, actionability, high penetrance, and secondary testing to confirm positive findings.}, } @article {pmid40426669, year = {2025}, author = {Eisen, A}, title = {Amyotrophic Lateral Sclerosis: Recent Considerations for Diagnosis, Pathogenesis and Therapy.}, journal = {Brain sciences}, volume = {15}, number = {5}, pages = {}, pmid = {40426669}, issn = {2076-3425}, abstract = {Amyotrophic lateral sclerosis (ALS/MND) is considered a uniquely human complex neurodegenerative disorder, presenting with a variety of clinical phenotypes, which include frontotemporal dementia [...].}, } @article {pmid40426231, year = {2025}, author = {Bergh, S and Casadei, N and Gabery, S and Simonsson, O and Duarte, JMN and Kirik, D and Nguyen, HP and Petersén, Å}, title = {TDP-43 overexpression in the hypothalamus drives neuropathology, dysregulates metabolism and impairs behavior in mice.}, journal = {Acta neuropathologica communications}, volume = {13}, number = {1}, pages = {119}, pmid = {40426231}, issn = {2051-5960}, mesh = {Animals ; *DNA-Binding Proteins/metabolism/genetics ; *Hypothalamus/pathology/metabolism ; Mice, Transgenic ; Mice ; Humans ; Neurons/pathology/metabolism ; Male ; Orexins/metabolism ; Hypothalamic Hormones/metabolism ; Melanins/metabolism ; Pituitary Hormones/metabolism ; Oxytocin/metabolism ; *Behavior, Animal/physiology ; Disease Models, Animal ; }, abstract = {TAR DNA-binding protein 43 (TDP-43) pathology is linked to the neurodegenerative disorders amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD) and Huntington disease (HD). Dysregulation of metabolism and emotion is shared across these disorders and may be caused by hypothalamic pathology. Inclusions with TDP-43 are present in the hypothalamus in clinical ALS, as well as selective loss of hypothalamic neurons expressing the metabolism and emotion regulating neuropeptides hypocretin (orexin), melanin-concentrating hormone (MCH) and oxytocin. We aimed to investigate whether there is a casual link between the effects of TDP-43 in the hypothalamus and the development of neuropathology, as well as changes in metabolism and behavior. We generated an adeno-associated viral (AAV) vector expressing human TDP-43 under the neuronal-specific synapsin promoter, which was injected bilaterally into the hypothalamus of wild-type FVB/N mice. TDP-43 overexpression resulted in hypothalamic pathology in a dose-dependent fashion replicating clinical pathology with hypothalamic atrophy and loss of hypocretin-, MCH- and oxytocin-expressing neurons. Nuclear and cytoplasmic inclusions of TDP-43 were found in the hypothalamus. Mice overexpressing TDP-43 in the hypothalamus developed metabolic dysregulation with hyperglycaemia independent of food intake. Additionally, mice overexpressing TDP-43 in the hypothalamus exhibited reduced motor activity and nesting ability, suggesting the development of an apathy-like phenotype. Taken together, AAV-vector mediated TDP-43 overexpression in the hypothalamus leads to neuropathology with the development of metabolic dysfunction and apathy-like behavior. These results indicate that TDP-43 can exert direct pathological effects in the hypothalamus, which may contribute to the development of the non-motor phenotype in TDP-43 proteinopathies.}, } @article {pmid40424919, year = {2025}, author = {Yamazaki, H and Takamatsu, N and Matsubara, T and Tani, M and Fukushima, K and Yoshida, T and Osaki, Y and Oki, R and Fujita, K and Nodera, H and Izumi, Y}, title = {Evaluation of the diagnostic performance of brachial plexus ultrasound in amyotrophic lateral sclerosis.}, journal = {Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology}, volume = {175}, number = {}, pages = {2110741}, doi = {10.1016/j.clinph.2025.2110741}, pmid = {40424919}, issn = {1872-8952}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnostic imaging/physiopathology ; Male ; Female ; Middle Aged ; *Brachial Plexus/diagnostic imaging/physiopathology ; Cross-Sectional Studies ; Ultrasonography/methods/standards ; Aged ; Retrospective Studies ; Adult ; }, abstract = {OBJECTIVE: This study aimed to assess the diagnostic performance of brachial plexus cross-sectional area (BP-CSA) measured by nerve ultrasound (NUS) for differentiating amyotrophic lateral sclerosis (ALS) from controls.

METHODS: A retrospective, cross-sectional study was conducted including patients with ALS and control patients who underwent NUS evaluation of the BP-CSA and the cervical nerve root CSA (C-CSA). Reference values for BP-CSA were built using reference cohort. Receiver operating characteristic curve analysis was performed in independent discovery and validation cohorts to assess the diagnostic performance of BP-CSA.

RESULTS: A total of 244 patients (114 ALS and 130 controls) were included. BP-CSA significantly correlated with body weight (coefficient = 0.50, p < 0.001). After adjusting for body weight, BP-CSA values were significantly lower in patients with ALS than controls (p < 0.001). Adjusted BP-CSA showed superior diagnostic performance compared to C-CSA, with area under the curve values of 0.75 (95 % CI: 0.64-0.86) and 0.78 (95 % CI: 0.68-0.88) in the discovery and validation cohorts, respectively.

CONCLUSIONS: BP-CSA, when adjusted for body weight, shows reliable performance in diagnosing ALS.

SIGNIFICANCE: This study highlights the clinical value of BP-CSA as a potential ALS diagnostic biomarker and underscores its superiority over cervical nerve root measurements.}, } @article {pmid40424855, year = {2025}, author = {Mrkela, M and Rodrigues, M and Naidoo, S and Devaux, JBL and Kirk, SE and Vinnakota, C and Buchanan, CM and Mulroy, D and Fraser, H and Jacobsen, JC and Wyatt, H and Drake, K and Parker, E and Potter, H and Henden, L and McCann, EP and Williams, KL and Henders, AK and Roxburgh, RH and Scotter, EL}, title = {The genetics of motor neuron disease in New Zealand.}, journal = {Journal of the neurological sciences}, volume = {474}, number = {}, pages = {123472}, doi = {10.1016/j.jns.2025.123472}, pmid = {40424855}, issn = {1878-5883}, mesh = {Humans ; New Zealand/epidemiology ; Male ; Female ; *Motor Neuron Disease/genetics/epidemiology ; Middle Aged ; Aged ; Superoxide Dismutase-1/genetics ; Adult ; C9orf72 Protein/genetics ; *Genetic Predisposition to Disease/genetics ; Dynactin Complex/genetics ; Aged, 80 and over ; }, abstract = {Motor neuron disease (MND) is a group of adult-onset neurodegenerative diseases characterised by progressive motor neuron degeneration, of which amyotrophic lateral sclerosis (ALS) is the most common. MND is clinically heterogeneous with complex etiology, caused by or associated with over 40 different genes and multiple environmental risk factors. New Zealand has one of the highest global incidence and mortality rates of MND, however the reasons are unknown. We sought to identify the frequencies of genetic variants in known MND-linked genes among people with MND in New Zealand. We enrolled 184 participants: 149 with a clinical diagnosis of MND (128 sporadic, 21 familial) and 35 clinically unaffected but at-risk individuals. Participants' DNA was screened for genetic variation in 46 MND-associated genes using Sanger sequencing, Illumina SNP microarray, repeat-primed PCR for C9orf72, and an Invitae gene panel. Clinical phenotypes mirrored European trends: males and spinal-onset cases had earlier disease onset. Thirty-three participants (17.9%) carried known pathogenic variants: 24 had C9orf72 repeat expansions, and 9 had pathogenic SOD1 variants (p.(Ile114Thr) and p.(Glu101Gly)). All New Zealand SOD1 p.(Ile114Thr) cases (n = 4) were distantly related to each other and to over 30 Australian cases with the same variant. Variants of interest were found in 14 participants with the splicing variants DCTN1:c.279+1G>C and ATP13A2:c.2412G>A, p.(Lys804=) subject to further study. Notably, 48.4% of pathogenic variants were in pre-symptomatic, unaffected individuals with family history, highlighting the importance of offering cascade testing and symptom surveillance for families, particularly as gene-specific treatments emerge.}, } @article {pmid40422218, year = {2025}, author = {Saxena, S and Arnold, WD}, title = {Current Challenges in Elucidating ALS Disease Mechanisms and Therapeutic Advances.}, journal = {Cells}, volume = {14}, number = {10}, pages = {}, pmid = {40422218}, issn = {2073-4409}, mesh = {Animals ; Humans ; *Amyotrophic Lateral Sclerosis/therapy/pathology/genetics ; }, abstract = {As a researcher and a physician working together to combat amyotrophic lateral sclerosis (ALS), we are acutely aware of both the urgent need for innovation and the persistent divide between laboratory discoveries and clinical care [...].}, } @article {pmid40422183, year = {2025}, author = {Verde, EM and Secco, V and Ghezzi, A and Mandrioli, J and Carra, S}, title = {Molecular Mechanisms of Protein Aggregation in ALS-FTD: Focus on TDP-43 and Cellular Protective Responses.}, journal = {Cells}, volume = {14}, number = {10}, pages = {}, pmid = {40422183}, issn = {2073-4409}, support = {SUMOsolvable//AriSLA/ ; AHA MCA 2022//Giovanni Armenise-Harvard Foundation and AirAlzh/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism/pathology/genetics ; *DNA-Binding Proteins/metabolism/genetics ; *Frontotemporal Dementia/metabolism/pathology/genetics ; *Protein Aggregates ; *Protein Aggregation, Pathological/metabolism ; Animals ; Protein Processing, Post-Translational ; }, abstract = {Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD) are two neurodegenerative disorders that share common genes and pathomechanisms and are referred to as the ALS-FTD spectrum. A hallmark of ALS-FTD pathology is the abnormal aggregation of proteins, including Cu/Zn superoxide dismutase (SOD1), transactive response DNA-binding protein 43 (TDP-43), fused in sarcoma/translocated in liposarcoma (FUS/TLS), and dipeptide repeat proteins resulting from C9orf72 hexanucleotide expansions. Genetic mutations linked to ALS-FTD disrupt protein stability, phase separation, and interaction networks, promoting misfolding and insolubility. This review explores the molecular mechanisms underlying protein aggregation in ALS-FTD, with a particular focus on TDP-43, as it represents the main aggregated species inside pathological inclusions and can also aggregate in its wild-type form. Moreover, this review describes the protective mechanisms activated by the cells to prevent protein aggregation, including molecular chaperones and post-translational modifications (PTMs). Understanding these regulatory pathways could offer new insights into targeted interventions aimed at mitigating cell toxicity and restoring cellular function.}, } @article {pmid40421380, year = {2025}, author = {Park, S and Park, SK and Blair, P and Liebman, SW}, title = {An adenine model of inborn metabolism errors alters TDP-43 aggregation and reduces its toxicity in yeast revealing insights into protein misfolding diseases.}, journal = {Microbial cell (Graz, Austria)}, volume = {12}, number = {}, pages = {119-130}, pmid = {40421380}, issn = {2311-2638}, support = {P20 GM130459/GM/NIGMS NIH HHS/United States ; R35 GM136229/GM/NIGMS NIH HHS/United States ; }, abstract = {TDP-43 is linked to human diseases such as amyotrophic lateral sclerosis (ALS) and frontotemporal degeneration (FTD). Expression of TDP-43 in yeast is known to be toxic, cause cells to elongate, form liquid-like aggregates, and inhibit autophagy and TOROID formation. Here, we used the apt1∆ aah1∆ yeast model of inborn errors of metabolism, previously shown to lead to intracellular adenine accumulation and adenine amyloid-like fiber formation, to explore interactions with TDP-43. Results show that the double deletion shifts the TDP-43 aggregates from liquid-like droplets toward a more amyloid-like state. At the same time the deletions reduce TDP-43's effects on toxicity, cell morphology, autophagy, and TOROID formation without affecting the level of TDP-43. This suggests that the liquid-like droplets rather than amyloid-like TDP-43 aggregates are responsible for the deleterious effects in yeast. How the apt1∆ aah1∆ deletions alter TDP-43 aggregate formation is not clear. Possibly, it results from adenine and TDP-43 fiber interactions as seen for other heterologous fibers. This work offers new insights into the potential interactions between metabolite-based amyloids and pathological protein aggregates, with broad implications for understanding protein misfolding diseases.}, } @article {pmid40420932, year = {2025}, author = {Farsakoury, R and Nashwan, AJ}, title = {Revitalizing upper blepharoplasty: Preserving volume.}, journal = {World journal of clinical cases}, volume = {13}, number = {15}, pages = {100563}, pmid = {40420932}, issn = {2307-8960}, abstract = {Blepharoplasty is a frequently performed aesthetic surgery today aimed at enhancing eyelid appearance and correcting age-related changes. The traditional method of subtraction blepharoplasty, which involved removing fat and excess skin, is now considered outdated. This letter explores Gorgy et al's commentary on Miotti et al's study, highlighting a shift in upper eyelid blepharoplasty towards a more conservative, volume-preserving approach. The study systematically reviewed 10 publications, including three retrospective studies, five comparative studies, and two clinical trials. It emphasizes the trend towards preserving the patient's natural anatomy and focusing on enhancement rather than alteration. However, the study's limitations, such as the lack of long-term comparative research, a relatively small sample size, and a single-center design, indicate that further research with extended follow-up is necessary to validate the safety and effectiveness of these techniques. The focus is increasingly on preserving and augmenting volume in upper blepharoplasty rather than removing tissue.}, } @article {pmid40420561, year = {2025}, author = {Harkey, BA and Distefano, S and Pagliaro, JA and Heyd, L and Chase, M and Igne, C and Yu, H and Sherman, AV and Dagostino, D and Tustison, E and Changkuon, G and Hall, M and Kittle, G and Connolly, MR and Giacomelli, E and Scirocco, E and Berry, JD and Babu, S and Shefner, J and Macklin, EA and Chibnik, LB and De Mattos, A and Drake, K and Kamp, C and McGarry, A and Torti, M and Small, C and Bulat, A and Cudkowicz, ME and Paganoni, S and , }, title = {Operational Development and Launch of an Adaptive Platform Trial in Amyotrophic Lateral Sclerosis: Processes and Learnings From the First Four Regimens of the HEALEY ALS Platform Trial.}, journal = {Muscle & nerve}, volume = {72}, number = {2}, pages = {294-305}, doi = {10.1002/mus.28442}, pmid = {40420561}, issn = {1097-4598}, support = {//Sean M. Healey and AMG Center/ ; //Tackle ALS/ ; //ALS Finding a Cure/ ; //The ALS Association/ ; //ALS ONE/ ; //The Arthur M. Blank Family Foundation/ ; //Muscular Dystrophy Association/ ; //UCB/ ; //Biohaven Pharmaceuticals Inc/ ; //Clene Nanomedicine/ ; //Prilenia Therapeutics/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/drug therapy ; Humans ; Male ; Female ; *Adaptive Clinical Trials as Topic/methods ; }, abstract = {INTRODUCTION/AIMS: Platform trials present several advantages over traditional interventional clinical trials. Here, we provide a detailed description of the operational framework of the HEALEY ALS Platform Trial.

METHODS: Platform-level procedures for regulatory oversight, safety, and site management were developed prior to trial launch. Central vendors and a single Institutional Review Board (sIRB) were used. An Investigational New Drug (IND) application was submitted for the master protocol, and each regimen was added as an amendment.

RESULTS: The HEALEY ALS Platform Trial was launched in 2020. Fifty-four geographically diverse sites from the Northeast ALS Consortium (NEALS), all highly experienced in ALS care and research, were selected. Three investigational products were selected to launch concurrently at the start of the trial as individual regimens. A fourth investigational product was selected and added to the trial after the initial launch. The Master Protocol and the first three regimens (Regimens A-C) were sIRB approved in 120 days. sIRB amendment for Regimen D was approved in 21 days. Enrollment for regimens A-C was completed in 15 months, whereas Regimen D was completed in 11 months from the start of enrollment. Results of all regimens were available within approximately 2 years from the initial trial launch.

DISCUSSION: The HEALEY ALS Platform Trial capitalized on the benefits of the platform approach, including an adaptable operational infrastructure, concurrent enrollment into four distinct regimens, and an accelerated start-up time for a new regimen added after initial trial launch.}, } @article {pmid40419749, year = {2025}, author = {Monteiro Neto, JR and de Souza, GF and Dos Santos, VM and de Holanda Paranhos, L and Ribeiro, GD and Magalhães, RSS and Queiroz, DD and Eleutherio, ECA}, title = {SOD1, A Crucial Protein for Neural Biochemistry: Dysfunction and Risk of Amyotrophic Lateral Sclerosis.}, journal = {Molecular neurobiology}, volume = {}, number = {}, pages = {}, pmid = {40419749}, issn = {1559-1182}, support = {201.174/2022//Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro/ ; 201.174/2022//Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro/ ; 201.174/2022//Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro/ ; 201.174/2022//Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro/ ; 201.174/2022//Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro/ ; 201.174/2022//Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro/ ; 201.174/2022//Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro/ ; 201.174/2022//Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro/ ; PROBRAL 88881.986154/2024-01//CAPES-DAAD/ ; PROBRAL 88881.986154/2024-01//CAPES-DAAD/ ; PROBRAL 88881.986154/2024-01//CAPES-DAAD/ ; PROBRAL 88881.986154/2024-01//CAPES-DAAD/ ; PROBRAL 88881.986154/2024-01//CAPES-DAAD/ ; PROBRAL 88881.986154/2024-01//CAPES-DAAD/ ; PROBRAL 88881.986154/2024-01//CAPES-DAAD/ ; PROBRAL 88881.986154/2024-01//CAPES-DAAD/ ; 309635/2023-3//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; 309635/2023-3//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; 309635/2023-3//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; 309635/2023-3//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; 309635/2023-3//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; 309635/2023-3//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; 309635/2023-3//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; 309635/2023-3//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; }, abstract = {Neurons are very susceptible to oxidative stress. They are the major consumers of oxygen in the brain, which is used to provide energy through oxidative phosphorylation, the major source of reactive oxygen species (ROS). In addition, compared to other tissues, neurons have lower levels of catalase and glutathione and increased susceptibility to lipid peroxidation due to the elevated levels of unsaturated fatty acids. These characteristics increasingly emphasize the antioxidant enzyme Cu/Zn superoxide dismutase 1 (SOD1) to maintain neuronal redox homeostasis. In the last decade, SOD1 gained additional roles which are also important to the metabolism of neurons. SOD1 controls the production of ROS by the electron transport chain, activates the expression of genes involved in the protection against oxidative stress, and regulates the shift from oxidative to fermentative metabolism involved in astrocyte-neuron metabolic cooperation. Furthermore, impaired interaction between the phosphatase calcineurin and SOD1 seems to result in TDP-43 hyperphosphorylation, the main proteinopathy found in amyotrophic lateral sclerosis (ALS) patients. However, this enzyme is ubiquitously expressed, mutated, and damaged forms of SOD1 cause disease in motor neurons. In this review, we discuss the pivotal functions of SOD1 in neuronal biochemistry and their implications for ALS.}, } @article {pmid40417702, year = {2025}, author = {Hoang, K and Prayotamornkul, S and Kuo, CY and Jang, H and Shi, L}, title = {Optical imaging of metabolic dynamics in ALS under methionine regulation.}, journal = {Journal of biomedical optics}, volume = {30}, number = {Suppl 2}, pages = {S23906}, pmid = {40417702}, issn = {1560-2281}, support = {R01 GM149976/GM/NIGMS NIH HHS/United States ; R21 NS125395/NS/NINDS NIH HHS/United States ; U01 AI167892/AI/NIAID NIH HHS/United States ; R01 NS111039/NS/NINDS NIH HHS/United States ; }, mesh = {*Amyotrophic Lateral Sclerosis/metabolism/diagnostic imaging ; *Methionine/metabolism/pharmacology ; Humans ; *Optical Imaging/methods ; Mitochondria/metabolism ; Reactive Oxygen Species/metabolism ; Oxidative Stress ; Spectrum Analysis, Raman/methods ; Cytochromes c/metabolism ; Imaging, Three-Dimensional ; Oxidation-Reduction ; }, abstract = {SIGNIFICANCE: Excessive reactive oxygen species (ROS) in dysfunctional mitochondria, combined with inefficient antioxidant defenses, can drive amyotrophic lateral sclerosis (ALS) progression. L-methionine (Met) can neutralize ROS by modulating metabolism and activating antioxidants; however, its impact on ALS remains unknown.

AIM: We aim to investigate the influence of excess Met on cellular metabolism and ROS accumulation and its role in ALS using multimodal optical imaging techniques.

APPROACH: We applied deuterium oxide-probed stimulated Raman scattering imaging to study metabolic changes of lipids, proteins, and cytochrome c and two-photon excitation fluorescence imaging to assess mitochondrial redox state (nicotinamide adenine dinucleotide and flavin adenine dinucleotide ratio) in ALS cellular models under excess Met treatment. With three-dimensional (3D) image reconstruction, we investigated morphological changes of lipid droplets (LDs) and stress granules (SGs) in ALS models.

RESULTS: Excess Met not only promoted syntheses of lipids and unsaturated lipid membranes but also reduced protein synthesis, cytochrome c oxidation, and oxidative stress. Moreover, 3D image reconstruction showed that LDs increased in volume and number to promote cellular repair, whereas SGs decreased in volume but increased in number in response to reduced cellular stress.

CONCLUSIONS: Excess Met offers a protective mechanism against oxidative stress and promotes cellular repair in ALS.}, } @article {pmid40417478, year = {2024}, author = {Marchal, N and Janes, WE and Earwood, JH and Mosa, ASM and Popescu, M and Skubic, M and Song, X}, title = {Integrating Multi-sensor Time-series Data for ALSFRS-R Clinical Scale Predictions in an ALS Patient Case Study.}, journal = {AMIA ... Annual Symposium proceedings. AMIA Symposium}, volume = {2024}, number = {}, pages = {788-797}, pmid = {40417478}, issn = {1942-597X}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/physiopathology ; *Monitoring, Ambulatory/methods ; Pilot Projects ; }, abstract = {Clinical tools for tracking functional decline in amyotrophic lateral sclerosis (ALS) rely on in-clinic guided assessments, such as the gold standard ALS Functional Rating Scale Revised (ALSFRS-R) instrument, thus limiting the frequency of collection and potentially delaying needed treatments. As such, ALS clinicians may miss subtle yet critical shifts inpatient health -pointing to the needfor objective and continuous capturing of day-to-day functional status. In-home health sensors could supplement clinical instruments with more frequent, quantitative measurements as early indicators of change. Using the XGBoost regressor in base learning, we explore interpolation techniques for aligning monthly ALSFRS-R assessment targets with high frequency sensor-based health features. We evaluated 9 interpolation models, which demonstrate superior prediction of ALSFRS-R scores compared to traditional clinical scale estimates based on linear slope. This pilot work provides a practical approach of modeling mixed-frequency data and shows the potential of using sensor-based health estimates as sensitive prognostic markers.}, } @article {pmid40415670, year = {2025}, author = {Uskun, E and Turkmenel, N and Kutluhan, S}, title = {Cross-cultural adaptation and psychometric evaluation of a Turkish version of the Amyotrophic Lateral Sclerosis-Specific Quality of Life-Short Form.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {26}, number = {5-6}, pages = {526-534}, doi = {10.1080/21678421.2025.2507177}, pmid = {40415670}, issn = {2167-9223}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/psychology/diagnosis ; *Quality of Life/psychology ; Female ; Male ; Middle Aged ; Turkey ; *Psychometrics/methods ; Reproducibility of Results ; Adult ; Aged ; *Cross-Cultural Comparison ; Surveys and Questionnaires ; }, abstract = {Objective: This study aimed to evaluate the validity and reliability of the Turkish version of the Amyotrophic Lateral Sclerosis Specific Quality of Life Instrument Short Form (ALSSQOL-SF), a quality-of-life scale originally developed by Simons et al., for Turkish Amyotrophic Lateral Sclerosis (ALS) patients. Methods: Using a rigorous six-step translation process, the scale was adapted without altering any items to maintain linguistic and cultural equivalence. The study included 100 patients diagnosed with ALS, aged 18 years and older, and native Turkish speakers. Results: Psychometric evaluations revealed strong content validity (CVI: 100%) and high internal consistency (Cronbach's alpha: 0.86 for the overall scale, 0.74-0.95 for subscales). Item-total correlation coefficients, except for three items, exceeded 0.20, and removing these items did not improve the scale's reliability, preserving the scale's integrity. Construct validity was supported by significant correlations with the Short Form 12 Health Survey Questionnaire (SF-12) and ALS Functional Rating Scale Revised (ALSFRS-R), confirming the scale's ability to assess physical and mental health in ALS patients. Exploratory factor analysis showed a 6-factor structure consistent with the original structure. Conclusion: Turkish version of ALSSQOL-SF (ALSSQOL-SF-Tr) is a reliable and valid instrument for assessing the quality of life in Turkish ALS patients. Its application in clinical and research settings can help evaluate patient needs and improve disease management.}, } @article {pmid40415381, year = {2025}, author = {Pretalli, JB and Vernerey, D and Evrard, P and Pozet, A and Clairet, AL and Benoist, S and Karoui, M and Cotte, E and Heyd, B and Lakkis, Z and , }, title = {Intraoperative indocyanine green fluorescence angiography in colorectal surgery to prevent anastomotic leakage: A single-blind phase III multicentre randomized controlled trial (FLUOCOL-01/FRENCH 21/GRECCAR 19 intergroup trial).}, journal = {Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland}, volume = {27}, number = {5}, pages = {e70119}, pmid = {40415381}, issn = {1463-1318}, support = {PHRC-K-20-044//Programme Hospitalier de Recherche Clinique-Cancer/ ; //French Ministry of Health/ ; }, mesh = {Female ; Humans ; Male ; Anastomosis, Surgical/adverse effects/methods ; *Anastomotic Leak/prevention & control/etiology ; Clinical Trials, Phase III as Topic ; Colon/surgery/blood supply ; *Colorectal Neoplasms/surgery ; Colorectal Surgery/methods ; Coloring Agents ; *Fluorescein Angiography/methods ; France ; *Indocyanine Green ; *Intraoperative Care/methods ; Multicenter Studies as Topic ; Randomized Controlled Trials as Topic ; Single-Blind Method ; }, abstract = {AIM: Anastomotic leak (AL) is a major problem in colorectal surgery, and its prevention is crucial for patient safety. The scientific literature shows that optimal anastomotic perfusion is essential for anastomotic healing. However, in cases of left colon or rectal cancer requiring high vessel ligation for oncological reasons, anastomotic blood supply relies mainly on the pericolic arterial arcades. Consequently, assessing anastomotic perfusion using intraoperative fluorescence angiography with indocyanine green might be relevant to reduce the risk of AL. Although evidence of its positive impact on the risk of AL is growing in the literature, most studies are descriptive prospective cohorts or retrospective comparative series with controversial findings. Furthermore, no other studies specifically address left-sided colon or high rectal tumours. FLUOCOL-1 is a large multicentre randomized controlled trial (RCT) that aims to demonstrate that assessing anastomotic perfusion using intraoperative fluorescence angiography with indocyanine green will reduce ALs in left-sided or high anterior resections with intraperitoneal anastomosis METHOD: FLUOCOL-1 is a French multicentre, single-blind, randomized, two-arm, phase III superiority clinical trial. Patients will be randomized in a 1:1 ratio to either the intervention group (FLUO+) or the control group (FLUO-). A total of 1010 patients will be randomized. The primary endpoint is the occurrence of an AL within 90 days postsurgery. AL is defined as any anastomotic dehiscence with leakage into the pelvic cavity diagnosed by imaging or surgical exploration, or any isolated pelvic organ-space infection with no evidence of fistula, as defined by the International Study Group of Rectal Cancer.

DISCUSSION: Prevention of AL is one of the most important questions to be addressed in colorectal surgery. The FLUOCOL-1 multicentre RCT described herein aims to demonstrate that assessment of anastomotic perfusion using intraoperative fluorescence angiography with indocyanine green will reduce ALs in certain resections with intraperitoneal anastomosis.}, } @article {pmid40414828, year = {2025}, author = {Kim, MS and Yoo, SH and Kim, KH and Cho, B and Lee, SY}, title = {Telemedicine Experiences of People Living with Amyotrophic Lateral Sclerosis at Home in South Korea.}, journal = {Yonsei medical journal}, volume = {66}, number = {6}, pages = {366-373}, pmid = {40414828}, issn = {1976-2437}, support = {RS-2021-KH120239//Patient-Centered Clinical Research Coordinating Center (PACEN)/Korea ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy ; Republic of Korea ; *Telemedicine ; Middle Aged ; Female ; Male ; Aged ; Cross-Sectional Studies ; Retrospective Studies ; Home Care Services ; }, abstract = {PURPOSE: Telemedicine is advantageous in providing medical care to patients with mobility difficulties. This single-center study aimed to report on the provision of video televisits to people living with amyotrophic lateral sclerosis (pALS, ALS) who were registered with a home-based medical care (HBMC) team in a tertiary hospital in South Korea.

MATERIALS AND METHODS: A retrospective cross-sectional study was conducted for pALS provided with video televisits by the HBMC team between July 2020 and February 2023. The patients' demographics, disease status, mobility level, and supportive care equipment were investigated. The main issues discussed at televisits were investigated.

RESULTS: During the 32-month study period, video televisits were provided to 69 (81.2%) of the 85 pALS registered with the HBMC team. Their median (interquartile range) age was 66 (57-71) years, and 66.7% were aged 60 years or older. At the time of the televisits, 71.0% were non-ambulatory and 27.5% were at an assisted ambulatory level. Furthermore, 82.6% were receiving nutritional support with a nasogastric or gastrostomy tube, and 78.3% had received either non-invasive positive pressure ventilation (43.5%) or tracheostomy invasive ventilation (34.8%). Common issues addressed on televisits were disease-related symptoms (100%), management of supportive care equipment (92.8%), acute health issues (52.2%), and advance care planning (ACP) including goal of care discussion (14.5%).

CONCLUSION: Video telemedicine is feasible for pALS, including older adults with limited mobility due to muscle weakness or reliance on various supportive care equipment. Video televisits allow for a variety of discussions, ranging from acute health issues to ACP.}, } @article {pmid40414644, year = {2025}, author = {Manusha, S and Varsha, N and Varshini, R and Sivamani, Y and Pokkuluri, KS and Elayaperumal, S}, title = {Altered microbiome influence on the enteric neuromuscular system in amyotrophic lateral sclerosis (ALS).}, journal = {International review of neurobiology}, volume = {180}, number = {}, pages = {95-123}, doi = {10.1016/bs.irn.2025.04.006}, pmid = {40414644}, issn = {2162-5514}, mesh = {*Amyotrophic Lateral Sclerosis/microbiology/physiopathology ; Humans ; *Gastrointestinal Microbiome/physiology ; *Enteric Nervous System/physiopathology/microbiology ; *Dysbiosis/physiopathology ; Animals ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurological disease marked by the degeneration of motor neurons, leading to muscle weakness and paralysis. While the cause of ALS is uncertain, research indicates that changes in the gut microbiome may influence the disease's progression. This chapter explores how alterations in gut microbiota affect the enteric neuromuscular system (ENS) in ALS. In ALS patients, disrupted gut microbiota are linked to the brain-gut axis, impacting both gastrointestinal function and neuronal health. Studies show that microbial changes are associated with inflammation, immune instability, and neurodegeneration, which exacerbate the disease. Gastrointestinal issues like constipation and dysphagia in ALS are tied to ENS dysregulation. Understanding the connections between the gut microbiome, ENS, and central nervous system (CNS) may lead to novel therapies targeting neurodegeneration and microbial dysbiosis in ALS.}, } @article {pmid40414240, year = {2025}, author = {Suzuki, N and Nishiyama, A and Ebihara, S and Aoki, M}, title = {Jacifusen for FUS-ALS: molecular effects and clinical outcomes in a case series.}, journal = {Lancet (London, England)}, volume = {405}, number = {10494}, pages = {2028-2030}, doi = {10.1016/S0140-6736(25)01038-4}, pmid = {40414240}, issn = {1474-547X}, } @article {pmid40414239, year = {2025}, author = {Shneider, NA and Harms, MB and Korobeynikov, VA and Rifai, OM and Hoover, BN and Harrington, EA and Aziz-Zaman, S and Singleton, J and Jamil, A and Madan, VR and Lee, I and Andrews, JA and Smiley, RM and Alam, MM and Black, LE and Shin, M and Watts, JK and Walk, D and Newman, D and Pascuzzi, RM and Weber, M and Neuwirth, C and Da Cruz, S and Soriano, A and Lane, R and Henry, S and Mathews, J and Jafar-Nejad, P and Norris, D and Rigo, F and Brown, RH and Miller, S and Crean, R and Bennett, CF}, title = {Antisense oligonucleotide jacifusen for FUS-ALS: an investigator-initiated, multicentre, open-label case series.}, journal = {Lancet (London, England)}, volume = {405}, number = {10494}, pages = {2075-2086}, doi = {10.1016/S0140-6736(25)00513-6}, pmid = {40414239}, issn = {1474-547X}, support = {R01 NS111990/NS/NINDS NIH HHS/United States ; TL1 TR001875/TR/NCATS NIH HHS/United States ; }, mesh = {Humans ; Female ; Male ; *RNA-Binding Protein FUS/genetics ; Middle Aged ; *Amyotrophic Lateral Sclerosis/drug therapy/genetics ; *Oligonucleotides, Antisense/therapeutic use/administration & dosage/adverse effects ; Injections, Spinal ; Adult ; *Oligonucleotides/therapeutic use/administration & dosage/adverse effects ; Treatment Outcome ; Aged ; }, abstract = {BACKGROUND: Pathogenic variants of fused in sarcoma (FUS) cause amyotrophic lateral sclerosis (FUS-ALS), with evidence of gain of function. Jacifusen is an antisense oligonucleotide targeting FUS pre-mRNA, previously shown to delay neurodegeneration in a mouse model and potentially slow functional decline in a first-in-human study. Here, we sought to further evaluate use of jacifusen as a treatment for FUS-ALS.

METHODS: This expanded access programme was conducted through a series of single-patient investigational new drug applications at five sites (four hospitals in the USA and one in Switzerland). Participants carried a FUS variant and had clinical evidence of motor neuron disease onset or electrophysiological abnormalities, if not a diagnosis of ALS. Participants were ineligible if chronically ventilated with tracheostomy. Enrolled sequentially, participants received serial intrathecal injections of jacifusen over 2·8-33·9 months. Based on multiple ascending doses of jacifusen (from 20 mg to 120 mg), successive protocols were modified as safety and other data were acquired, with the last participants enrolled receiving 120 mg doses monthly from the start of their treatment. Safety was assessed using the Common Terminology Criteria for Adverse Events version 4.0 and standard cerebrospinal fluid (CSF) metrics. Concentration of neurofilament light chain (NfL) in CSF was used as a biomarker of axonal injury and neurodegeneration, and the ALS Functional Rating Scale-Revised (ALSFRS-R) score was used as an overall measure of motor function. Biochemical analysis and immunohistochemical staining were done on post-mortem CNS tissues to quantify FUS protein expression and assess the burden of FUS pathology.

FINDINGS: Between June 11, 2019, and June 2, 2023, we recruited 12 participants (median age 26 years [range 16-45]; seven [58%] were female and five [42%] were male) into the expanded access programme. Transient elevations in cell counts or total protein concentration in CSF (six [50%] participants) were unrelated to treatment duration. The most common adverse events were back pain (six [50%]), headache (four [33%]), nausea (three [25%]), and post-lumbar puncture headache (three [25%]). Two participant deaths were recorded during the programme, both thought to be unrelated to the investigational drug. The concentration of NfL in CSF was reduced by up to 82·8% after 6 months of treatment. Although most participants had continued functional decline (as measured by ALSFRS-R) after starting treatment with jacifusen, one showed unprecedented, objective functional recovery after 10 months, and another remained asymptomatic, with documented improvement in electromyographic abnormalities. Biochemical and immunohistochemical analysis of CNS tissue samples from four participants showed reduced FUS protein levels and an apparent decrease in the burden of FUS pathology.

INTERPRETATION: The findings suggest the safety and possible efficacy of jacifusen for treating FUS-ALS. The efficacy of jacifusen is being further evaluated in an ongoing clinical trial.

FUNDING: ALS Association, Project ALS, Ionis Pharmaceuticals, Tow Foundation, Nancy D Perlman and Thomas D Klingenstein Innovation Fund for Neurodegenerative Disease, National Institutes of Health, Angel Fund for ALS Research, Cellucci Fund for ALS Research, Max Rosenfeld ALS Fund, University of Minnesota, and the Muscular Dystrophy Association.}, } @article {pmid40413670, year = {2025}, author = {Montero-Odasso, M and Pieruccini-Faria, F and Black, SE and Binns, MA and Freedman, M and Grimes, DA and Hegele, RA and Haddad, SH and Lang, AE and Masellis, M and Mandzia, J and Beaton, D and Ramirez, J and Roberts, AC and McIlroy, W and Pasternak, SH and Zinman, L and Abrahao, A and Swartz, RH and Symons, S and Tan, B and Tartaglia, C and Son, S and Sakurai, R and Dilliott, A and Cornish, BF and Hezam, A and Strong, MJ and , and Bartha, R}, title = {Association between vascular risk factors burden and neurodegenerative diseases: results from ONDRI.}, journal = {Journal of neurology}, volume = {272}, number = {6}, pages = {418}, pmid = {40413670}, issn = {1432-1459}, mesh = {Humans ; Male ; Female ; Aged ; Cross-Sectional Studies ; *Neurodegenerative Diseases/epidemiology/diagnostic imaging/pathology ; Risk Factors ; Middle Aged ; *White Matter/diagnostic imaging/pathology ; *Cerebrovascular Disorders/epidemiology/diagnostic imaging ; Cognitive Dysfunction/epidemiology/diagnostic imaging ; Aged, 80 and over ; Cohort Studies ; Ontario/epidemiology ; Magnetic Resonance Imaging ; Diffusion Tensor Imaging ; }, abstract = {BACKGROUND: Vascular risk factors are common in older adults and contribute to brain damage, can manifest as increased white matter hyperintensities (WMH), and associated with future risk of stroke and dementia. However, their prevalence, effect across different neurodegenerative diseases, and association with WMH remains underexplored.

OBJECTIVE: To investigate the association between vascular risk burden, and brain white matter integrity, across five neurodegenerative conditions.

METHODS: Cross-sectional study including 520 participants from the Ontario Neurodegenerative Disease Research Initiative (ONDRI) cohorts: 126 with amnestic Mild Cognitive Impairment/Alzheimer's Disease (MCI/AD), 53 with Frontotemporal Dementia (FTD), 161 with Cerebrovascular Disease (CVD), 140 with Parkinson's Disease (PD), and 40 with Amyotrophic Lateral Sclerosis (ALS), along with 41 cognitively healthy controls. A vascular risk index (VRI, range 0-5) assessed hypertension, diabetes, dyslipidemia, obesity (BMI ≥ 30), and smoking history. Macro (WMH volume) and micro (Diffusion tensor imaging) white matter integrity were evaluated using 3-Tesla MRI. Associations were analyzed using multinomial logistic regression and ANCOVA, adjusting for age, sex, education, and APOE ε4 allele status.

RESULTS: Vascular risk factors, particularly hypertension and hypercholesterolemia, were more prevalent in the disease cohorts than controls. A higher VRI was significantly associated with MCI/AD (1.5-fold, p = 0.05), FTD (1.7-fold, p =0 .02), and CVD (2.6-fold, p < 0.005) cohorts. High VRI was associated with reduced macro and microstructural white matter integrity in the pooled sample (macro: p = 0.005; micro: p = 0.003), and separately in CVD (macro: p = 0.04; micro: p = 0.002). APOE ε4 status only mildly attenuated these associations.

CONCLUSION: Vascular risk burden is prevalent in neurocognitive syndromes including MCI/AD, FTD and CVD, and impacts white matter integrity. Future studies are needed to explore if vascular risk management may mitigate the consequences of neurodegeneration in these clinical groups.}, } @article {pmid40413526, year = {2025}, author = {Hawley, ZCE and Li, X and Bodnar, D and Gu, Y and Luo, Y and Ferretti, D and Sheehy, A and Driscoll, R and Zavodszky, MI and Cao, S and Isaza, I and Jandreski, L and Liu, Y and Carlile, T and Lo, SC and Grimard, A and Bourque, S and Utturkar, A and Desmarais, S and Arnold, HM and Huh, D and Guilmette, E and Kwon, DY}, title = {Viral-mediated knockdown of Atxn2 attenuates TDP-43 pathology and muscle dysfunction in the PFN1[C71G] ALS mouse model.}, journal = {Acta neuropathologica communications}, volume = {13}, number = {1}, pages = {116}, pmid = {40413526}, issn = {2051-5960}, mesh = {Animals ; *Amyotrophic Lateral Sclerosis/pathology/genetics/metabolism ; *Profilins/genetics/metabolism ; Mice, Transgenic ; Disease Models, Animal ; *DNA-Binding Proteins/metabolism/genetics ; Mice ; *Ataxin-2/genetics/metabolism ; Humans ; Spinal Cord/pathology/metabolism ; Gene Knockdown Techniques ; Muscle, Skeletal/pathology/metabolism ; Male ; Motor Neurons/pathology/metabolism ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by progressive motor neuron loss and muscle atrophy. Hyperphosphorylated aggregation of the RNA-binding protein, TDP-43, in the motor cortex and spinal cord are defining molecular features of ALS, suggesting TDP-43 dysfunction underlies disease pathogenesis. This phenomenon, however, has been difficult to recapitulate endogenously in animal models, impeding characterization of TDP-43 pathobiology in neurodegeneration. In this study, we report age-dependent accumulation of TDP-43 pathology in the spinal cord and progressive muscle-related deficits in transgenic mice expressing the ALS-associated PFN1[C71G] mutant protein. We show that transgenic neuronal expression of PFN1[C71G] induces early hyperphosphorylation of endogenous TDP-43 in the spinal cord that augments over time, preceding accumulation of insoluble non-phosphorylated TDP-43 and the manifestation of muscle denervation and motor dysfunction. Sustained knockdown of Atxn2 in the central nervous system (CNS) in pre-symptomatic PFN1[C71G] mice by AAV-driven expression of an artificial microRNA (AAV-amiR-Atxn2) reduces aberrant TDP-43 in the spinal cord, while delaying neurodegeneration and improving muscle and motor function. RNA-sequencing analysis of spinal cord samples from PFN1[C71G] mice and ALS donors show shared patterns of transcriptional perturbation, including a pro-inflammatory gene signature that is attenuated by AAV-amiR-Atxn2. Notably, impaired regulation of the PFN1[C71G] skeletal muscle transcriptome exceeds that of the spinal cord and is also improved by Atxn2 reduction in the CNS. Lastly, we find significant gene co-expression network homology between PFN1[C71G] mice and human ALS, with shared dysregulation of modules related to neuroinflammation and neuronal function and uncover novel hub genes that provide biological insight into ALS and potential drug targets that can be further investigated in this mouse model.}, } @article {pmid40413303, year = {2025}, author = {Yang, W and Luo, Z and Tang, X and Guo, J and Chen, X and Dong, Y and Sun, YM and Fan, D and Xu, K and Chen, Y and Zhang, M}, title = {Protein Structure-based FUS Mutational Subtypes Are Associated With Protein Mislocalization in Amyotrophic Lateral Sclerosis Patients.}, journal = {Molecular neurobiology}, volume = {}, number = {}, pages = {}, pmid = {40413303}, issn = {1559-1182}, support = {32301018//National Natural Science Foundation of China/ ; 82071430, 82371878//National Natural Science Foundation of China/ ; 2021YFA1302200//National Key Research and Development Program of China/ ; 22ZR1466400//Shanghai Municipal Natural Science Foundation General Program/ ; }, abstract = {The mislocalization of RNA-binding proteins (RBPs) from nucleus to cytoplasm and the formation of aggregates are hallmarks of neurodegeneration. Amyotrophic lateral sclerosis (ALS) disease-causing mutations in the fused in sarcoma (FUS) gene, encoding an RNA-binding protein, cluster at the C-terminal proline/tyrosine-nuclear localization signal (PY-NLS) domain, which is crucial for mediating nucleus-cytoplasm translocation by binding to Transportin-1. However, the mechanisms underlying heterogeneous protein mislocalization and age at onset (AAO) of ALS cases carrying FUS PY-NLS mutations remain unclear. Here, we screened FUS mutations in 416 ALS patients, and identified 12 patients carrying four FUS mutations at the p.R521 locus of PY-NLS domain (p.R521P, p.R521C, p.R521G, p.R521H), exhibiting highly variable AAO (20-56 years). AlphaFold-2 predicted protein structures classified FUS p.R521 mutants into alpha-helix containing (p.R521C, p.R521H) and alpha-helix disrupted (p.R521P, p.R521G) subgroups. Isothermal titration calorimetry experiment showed that the FUS alpha-helix disrupted subgroup had a reduced binding affinity with transportin-1, which is essential for mediating the nucleus-cytoplasm translocation. Furthermore, immunofluorescence in HEK-293 T and SH-SY5Y cells revealed more protein mislocalization in the FUS alpha-helix disrupted subgroup compared to the alpha-helix containing subgroup. FUS mislocalization status is also significantly associated with ALS AAO. Finally, the alpha-helix structure based FUS-ALS subgroups exhibited significantly different AAO (P = 0.036) in our cohort, but not in a Chinese cohort including published dataset. In summary, we showed highly diverse phenotypes in ALS patients with FUS R521 mutants, and implicated a link between genetic mutation related C-terminal structure with the status of FUS protein mislocalization.}, } @article {pmid40413059, year = {2025}, author = {Lopes, AMDS and Giacomini, S and Ulahannan, A and Darnac, C and Bugeia, S and Gutknecht, G and Colomer-Lahiguera, S and Spurrier-Bernard, G and Latifyan, S and Addeo, A and Michielin, O and Eicher, M}, title = {Acceptability of an Electronic Patient-Reported Outcomes-Based Model of Care to Monitor Symptoms Related to Cancer Treatment with Immune Checkpoint Inhibitors: Results from the IePRO Randomized Controlled Trial.}, journal = {Seminars in oncology nursing}, volume = {41}, number = {4}, pages = {151903}, doi = {10.1016/j.soncn.2025.151903}, pmid = {40413059}, issn = {1878-3449}, abstract = {OBJECTIVES: This study analyzed the acceptability of an electronic patient-reported outcomes measures-based model of care (IePRO MoC) and the usability of its complementary ePROM mobile app to monitor and manage symptoms related to immune checkpoint inhibitors. In this MoC, symptoms reported by patients treated at an outpatient clinic were reviewed by oncology triage nurses who provided symptom management interventions by telephone.

METHODS: As part of a larger intervention trial (ClinicalTrials.gov.NCT05530187) we conducted an abductive, semantic thematic analysis through semistructured interviews of patients participating in the intervention arm. Acceptability was deduced from Sekhon et al's (2017) Theoretical Framework of Acceptability completed with inductively generated themes. Usability analysis was guided by the mHealth App Usability Questionnaire's domains by Zhoul et al (2019).

RESULTS: A total of 17 interviews were performed. The IePRO MoC was reported to be an acceptable intervention. Patients expressed feeling safe and empowered due to continuous monitoring and timely support from nurses. Personalized support motivated patients to use the MoC throughout treatment. Some questioned the predefined response options of the app, and the standardized approach regarding notifications and monitoring requirements. Despite high app usability, some expressed discomfort from being frequently reminded of their illness and being confronted with questions about their sexuality and other intimate themes.

CONCLUSIONS: The feedback loop between patients and nurses facilitated the acceptability of the IePRO MoC. The app's usability further facilitated adherence to the MoC. A more personalized approach regarding the frequency of assessments and the way symptoms are conveyed is recommended to decrease discomfort and support the implementation of similar MoCs in the future.}, } @article {pmid40412724, year = {2025}, author = {Xu, Y and Hou, W and Gao, J and Wei, JC and Zhang, L}, title = {Letter to Alameddine et al's "Celiac disease associated with alopecia areata: A multicenter case-control study".}, journal = {Journal of the American Academy of Dermatology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jaad.2025.05.1405}, pmid = {40412724}, issn = {1097-6787}, } @article {pmid40412392, year = {2025}, author = {Yan, X and Kuster, D and Mohanty, P and Nijssen, J and Pombo-García, K and Garcia Morato, J and Rizuan, A and Franzmann, TM and Sergeeva, A and Ly, AM and Liu, F and Passos, PM and George, L and Wang, SH and Shenoy, J and Danielson, HL and Ozguney, B and Honigmann, A and Ayala, YM and Fawzi, NL and Dickson, DW and Rossoll, W and Mittal, J and Alberti, S and Hyman, AA}, title = {Intra-condensate demixing of TDP-43 inside stress granules generates pathological aggregates.}, journal = {Cell}, volume = {188}, number = {15}, pages = {4123-4140.e18}, pmid = {40412392}, issn = {1097-4172}, support = {R01 NS114289/NS/NINDS NIH HHS/United States ; R01 NS116176/NS/NINDS NIH HHS/United States ; }, mesh = {*DNA-Binding Proteins/metabolism/chemistry/genetics ; Humans ; Animals ; Mice ; *Stress Granules/metabolism ; *Protein Aggregation, Pathological/metabolism ; Oxidative Stress ; Protein Aggregates ; Disease Models, Animal ; Motor Neurons/metabolism ; Neurodegenerative Diseases/metabolism/pathology ; Protein Domains ; }, abstract = {Cytosolic aggregation of the nuclear protein TAR DNA-binding protein 43 (TDP-43) is associated with many neurodegenerative diseases, but the triggers for TDP-43 aggregation are still debated. Here, we demonstrate that TDP-43 aggregation requires a double event. One is up-concentration in stress granules beyond a threshold, and the other is oxidative stress. These two events collectively induce intra-condensate demixing, giving rise to a dynamic TDP-43-enriched phase within stress granules, which subsequently transition into pathological aggregates. Intra-condensate demixing of TDP-43 is observed in iPS-motor neurons, a disease mouse model, and patient samples. Mechanistically, intra-condensate demixing is triggered by local unfolding of the RRM1 domain for intermolecular disulfide bond formation and by increased hydrophobic patch interactions in the C-terminal domain. By engineering TDP-43 variants resistant to intra-condensate demixing, we successfully eliminate pathological TDP-43 aggregates in cells. We suggest that up-concentration inside condensates followed by intra-condensate demixing could be a general pathway for protein aggregation.}, } @article {pmid40412267, year = {2025}, author = {Tian, H and Huang, N and Chen, C and Yu, H and Ge, C}, title = {Flavor profiles and genetic basis differences of Lacticaseibacillus paracasei isolates from different isolations in fermented milk.}, journal = {International journal of food microbiology}, volume = {440}, number = {}, pages = {111274}, doi = {10.1016/j.ijfoodmicro.2025.111274}, pmid = {40412267}, issn = {1879-3460}, mesh = {*Cultured Milk Products/microbiology ; *Flavoring Agents/metabolism/chemistry ; Taste ; *Lacticaseibacillus paracasei/genetics/isolation & purification/metabolism/classification ; Fermentation ; Animals ; Food Microbiology ; Volatile Organic Compounds/metabolism/analysis ; *Milk/microbiology ; Ketones/metabolism/analysis ; Multigene Family ; }, abstract = {Lacticaseibacillus paracasei from diverse traditional fermented foods exhibit unique flavor profiles in dairy products. In this study, 101 Lacticaseibacillus isolates were categorized into four distinct classes, with those originating from fermented dairy products demonstrating the highest flavor diversity. Multivariate statistical analyses identified diacetyl, acetoin, and 2-nonanone as key volatile compounds characterizing ketone-type isolates. Further examination of two ketone-type isolates and one non-ketone-type isolate, isolated from kurut, sour porridge, and Huangjiu mash respectively, revealed their specific abilities to produce ketones, lactones, and alcohols. Genome comparison of ketone-type and non-ketone-type L. paracasei isolates revealed disparities in the cit gene cluster, als, and but genes within the citrate metabolic pathway. These findings provide novel insights into the flavor diversity and help identify potential key genes involved in flavor formation in L. paracasei isolates, thereby facilitating the application of L. paracasei isolates in fermented dairy products.}, } @article {pmid40411682, year = {2025}, author = {Jain, S and Das, D and Mukherjee, A and Roy, I}, title = {Inhibition of PolyGA Dipeptide Repeat Protein Aggregation by Nucleic Acid Aptamers in C9 Amyotrophic Lateral Sclerosis-Frontotemporal Dementia Models.}, journal = {Molecular neurobiology}, volume = {}, number = {}, pages = {}, pmid = {40411682}, issn = {1559-1182}, support = {BT/PR30896/BRB/10/1747/2018//Department of Biotechnology/ ; }, abstract = {Hexanucleotide (GGGGCC) repeat expansion in non-coding region of C9ORF72 is the main genetic cause of amyotrophic lateral sclerosis-frontotemporal dementia (ALS-FTD). Gain of toxic function, via RNA or proteins, or loss of function via haploinsufficiency, are probable mechanisms of disease progression. Expanded GGGGCC repeat codes for dipeptide repeat (DPR) proteins which form inclusions in the brain. Among all the dipeptides, aggregates formed by polyGA sequence are the most toxic. In this work, inhibition of aggregation of polyGA DPRs using aptamers has been explored as a therapeutic strategy to delay disease progression. Target-specific, high-affinity RNA aptamers were selected against monomeric (GA)30. Selected aptamers showed significant inhibition of aggregation of (GA)30 in vitro. Inhibitory RNA sequences were seen to form typical secondary structures which was missing in a non-inhibitory sequence. Some of the RNA aptamers showed increased solubilisation of DPRs formed by (GA)30 and (GA)60 in a neuronal cell model of ALS-FTD. Decreased aggregation was accompanied by lower oxidative stress and improved cell survival. Importantly, expression level of one of the markers of autophagy was significantly enhanced in the presence of aptamers, explaining lower aggregation observed in these cells. Thus, aptamers may be developed as potential therapeutic agents in C9 ALS-FTD.}, } @article {pmid40411245, year = {2025}, author = {Giacobbe, A and Hiana, J and Wang, O and Benatar, M and Wicks, P and Mascias Cadavid, J and Jhooty, S and McDermott, C and Pattee, G and Bertorini, T and Heiman-Patterson, T and Ratner, D and Barkhaus, P and Carter, G and Jackson, C and Denson, K and Brown, A and Armon, C and Sun, Y and Nguyen, A and Bedlack, R and Li, X}, title = {ALSUntangled #79: alpha-lipoic acid.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {}, number = {}, pages = {1-5}, doi = {10.1080/21678421.2025.2507166}, pmid = {40411245}, issn = {2167-9223}, abstract = {Alpha-lipoic acid (ALA) is a naturally occurring fatty acid. It serves as an essential cofactor for enzymatic reactions in mitochondrial energy production, is a potent antioxidant and has anti-inflammatory effects, which are plausible mechanisms in slowing ALS progression. In ALS preclinical studies, ALA slowed motor function decline and improved survival. There were self-reported cases of improved muscle strength in ALS patients when ALA was taken with numerous additional supplements, making it difficult to discern its efficacy. One small, 6-month open-label study showed improved quality of life, fatigue, and mood after participants took it with B vitamins and amino acids for the first 3 months. So far, no clinical trials have been published in people living with amyotrophic lateral sclerosis (PALS). Given the insufficient clinical data, we cannot endorse ALA and will support more research on its efficacy in slowing ALS progression.}, } @article {pmid40409555, year = {2025}, author = {Ma, G and Ruan, X and Yang, B and Li, N and Su, D and Sun, S and Chen, S and Xu, K and Ying, Z and Wang, H}, title = {Abnormal regulation of membrane-less organelles contributes to profilin1-associated ALS.}, journal = {The Journal of biological chemistry}, volume = {301}, number = {7}, pages = {110259}, pmid = {40409555}, issn = {1083-351X}, mesh = {*Profilins/metabolism/genetics ; *Amyotrophic Lateral Sclerosis/metabolism/pathology/genetics ; Humans ; Stress Granules/metabolism/pathology/genetics ; *Coiled Bodies/metabolism/pathology/genetics ; Actin Cytoskeleton/metabolism ; Animals ; }, abstract = {Profilin 1 (PFN1) is a key cytoskeletal protein that regulates actin dynamics by incorporating monomeric actin into linear filaments. PFN1 deletion or mutations have been linked to numerous neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). However, the contribution of PFN1 to neurodegenerative pathologies is poorly understood. Recent studies have implicated the role of aberrant cellular membrane-less organelles (MLOs) in neurodegenerative pathogenesis. Here, we demonstrate that PFN1 is involved in the assembly of MLOs, including Cajal bodies and Stress granules. Specifically, depletion of PFN1 leads to abnormal Cajal body accumulation and accelerated maturation into a gel-like state, consequently dysregulating snRNP biogenesis and impairing pre-mRNA splicing efficiency in both neuronal and non-neuronal cells. Similarly, we show that PFN1 knockdown accelerates the assembly of Stress granules in stressed cells. Furthermore, we demonstrate that the ALS-linked PFN1-C71 G mutant exhibits a loss of function in the context of MLO biogenesis. We further reveal that the PFN1 deficiency-induced Cajal body dysregulation, but not Stress granule assembly, is caused by cellular actin filament depolymerization. Importantly, the actin filament agonist CN04 rescues Cajal body properties in PFN1-depleted cells. Taken together, our findings shed light on the role of PFN1 in MLO biogenesis and suggest its involvement in neurodegenerative pathogenesis.}, } @article {pmid40409314, year = {2025}, author = {, and , }, title = {Safety and efficacy of trehalose in amyotrophic lateral sclerosis (HEALEY ALS Platform Trial): an adaptive, phase 2/3, double-blind, randomised, placebo-controlled trial.}, journal = {The Lancet. Neurology}, volume = {24}, number = {6}, pages = {500-511}, doi = {10.1016/S1474-4422(25)00173-5}, pmid = {40409314}, issn = {1474-4465}, mesh = {Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; *Amyotrophic Lateral Sclerosis/drug therapy ; Disease Progression ; Double-Blind Method ; Edaravone/therapeutic use ; *Neuroprotective Agents/therapeutic use ; Riluzole/therapeutic use ; Treatment Outcome ; *Trehalose/therapeutic use/adverse effects/administration & dosage ; }, abstract = {BACKGROUND: Trehalose is a disaccharide that activates autophagy pathways in animal models of neurodegenerative diseases, with the potential to catalyse clearance of toxic, misfolded proteins in motor neurons and slow disease progression in amyotrophic lateral sclerosis (ALS). We aimed to evaluate the safety and efficacy of trehalose in individuals with ALS.

METHODS: The HEALEY ALS Platform Trial is a perpetual, adaptive, phase 2/3, randomised, double-blind, multi-regimen trial conducted at 60 geographically diverse sites in the USA. In the current regimen, adults with clinically possible, probable, laboratory-supported probable, or definite ALS, defined by the revised El Escorial criteria, were randomly allocated (3:1), stratified by use of edaravone and riluzole, to receive trehalose 0·75 g per kg intravenously weekly over 24 weeks, or matching placebo. The primary outcome was a composite of the relative rate of disease progression, as measured by the Revised ALS Functional Rating Scale (ALSFRS-R), and survival over 24 weeks, estimated in a Bayesian shared-parameter model. The study included prespecified stopping rules for futility; interim analyses occurred every 12 weeks. The primary outcome was analysed according to the intention-to-treat principle in all participants in the trehalose group, the placebo group within the regimen, and placebo groups from other contributing regimens; the safety analysis population was comprised of all participants who initiated treatment. This study is registered with ClinicalTrials.gov, NCT05136885.

FINDINGS: Between Feb 21, 2022, and Feb 17, 2023, 1021 participants were screened for the platform trial and 171 were assigned to the trehalose regimen. Of these, 161 participants met eligibility criteria, with 120 randomly allocated to trehalose and 41 to regimen-specific placebo. 164 participants randomly allocated to placebo in other regimens were added for analysis (totalling 205 placebo recipients). The disease rate ratio for change in ALSFRS-R and survival was 0·87 (95% credible interval 0·665-1·102, posterior probability of superiority 0·877). Serious adverse events occurred in 19 (16%) participants in the trehalose group and three (7%) participants in the regimen-only placebo group, leading to premature discontinuations in 14 (12%) versus one (2%), respectively. Fatal treatment-emergent adverse events occurred in seven participants in the trehalose group and none in the regimen-only placebo group. No death was considered related to the trial drug. The most common cause of death was respiratory failure, consistent with the natural history of ALS.

INTERPRETATION: Trehalose was well tolerated but there was no evidence to suggest a difference in ALS disease progression compared with placebo in this study. No statistical benefit was seen in secondary clinical or biomarker measures, suggesting that trehalose at this dosage is unlikely to be efficacious for treatment of ALS.

FUNDING: AMG Charitable Foundation, Tackle ALS, the ALS Association, ALS Finding a Cure, the Muscular Dystrophy Association, ALS ONE, the Arthur M Blank Family Foundation, I AM ALS, Tambourine ALS Collaborative, and other community fundraising initiatives and donors. Study drug and partial regimen-related funding was provided by Seelos.}, } @article {pmid40409302, year = {2025}, author = {Fan, D}, title = {Innovative trial designs in amyotrophic lateral sclerosis: balancing efficiency and precision.}, journal = {The Lancet. Neurology}, volume = {24}, number = {6}, pages = {473-474}, doi = {10.1016/S1474-4422(25)00150-4}, pmid = {40409302}, issn = {1474-4465}, } @article {pmid40407667, year = {2025}, author = {Pérez-Bonilla, M and Díaz Borrego, P and Mora-Ortiz, M and Fernández-Baillo, R and Muñoz-Alcaraz, MN and Mayordomo-Riera, FJ and Girela López, E}, title = {Relationship Between Voice Analysis and Functional Status in Patients with Amyotrophic Lateral Sclerosis.}, journal = {Audiology research}, volume = {15}, number = {3}, pages = {}, pmid = {40407667}, issn = {2039-4330}, abstract = {Background: Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disease affecting both upper and lower motor neurons, with bulbar dysfunction manifesting in up to 80% of patients. Dysarthria, characterized by impaired speech production, is common in ALS and often correlates with disease severity. Voice analysis has emerged as a promising tool for detecting disease progression and monitoring functional status. Methods: This study investigates acoustic and biomechanical voice alterations in ALS patients and their association with clinical measures of functional independence. A descriptive observational case series study was conducted, involving 43 ALS patients and 43 age and sex matched controls with non-neurological voice disorders. Sustained vowel /a/ recordings were obtained and analyzed using Voice Clinical Systems[®] and Praat software (version 6.2.22). Biomechanical and acoustic parameters were correlated with ALS Functional Rating Scale-Revised (ALSFRS-R) and Barthel Index scores. Results: Significant differences were observed between ALS and control groups (elevated muscle force and tension and interedge distance in non-ALS individuals). Between bulbar and spinal ALS subtypes, elevated values were observed in certain parameters in Bulbar ALS patients, indicating irregular vocal fold contact and weakened phonatory control, while spinal ALS exhibited increased values, suggesting higher phonatory muscle tension. Elevated biomechanical parameters were significantly correlated with low ALSFRS-R scores, suggesting a possible relationship between voice measures and functional decline. However, acoustic measurements showed no relationship with performance status. Conclusions: These results highlight the potential of voice analysis as a non-invasive, objective tool for monitoring ALS stage and differentiating between subtypes. Further research is needed to validate these findings and explore their clinical applications.}, } @article {pmid40407286, year = {2025}, author = {Steenkjær, CH and Heintzelmann, MB and Obál, I and Andersen, G and Blicher, JU}, title = {An adapted Danish translation of the Center for Neurologic Study Lability scale.}, journal = {Danish medical journal}, volume = {72}, number = {5}, pages = {}, doi = {10.61409/A07240497}, pmid = {40407286}, issn = {2245-1919}, mesh = {Humans ; Denmark ; *Amyotrophic Lateral Sclerosis/psychology/complications/diagnosis ; *Multiple Sclerosis/psychology/complications/diagnosis ; *Translations ; Surveys and Questionnaires ; Female ; Male ; Middle Aged ; Adult ; Aged ; Translating ; }, abstract = {INTRODUCTION: Pathological crying and/or laughing (pseudobulbar affect (PBA)) are socially debilitating symptoms seen in many neurological diseases, such as stroke, multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS). One method for measuring the degree of PBA is the Center for Neurologic Study-Lability Scale (CNS-LS), a seven-item questionnaire validated for quantifying symptoms and supporting PBA diagnoses in ALS and MS. The aim of this study was to provide a Danish translation of the CNS-LS inspired by international guidelines on cross-cultural translation and adaptation of self-report measurements.

METHODS: Through a six-step process, the CNS-LS was translated and back-translated by four certified translators, followed by an expert committee examination. The translation was then field-tested by interviewing patients with ALS and MS after they had completed the CNS-LS. If at least 20% of participants found an item "unclear", it would be reevaluated.

RESULTS: Twelve patients with ALS patients and 30 patients with MS were tested and interviewed. None of the questionnaire items exceeded the 20% threshold for lack of clarity.

CONCLUSION: We present a Danish translation of the CNS-LS to facilitate better diagnosis and quantification of PBA symptoms in Danish patients with ALS or MS.

FUNDING: This study received funding from the PhD fellowship grant of Neuroscience Academy Denmark.

TRIAL REGISTRATION: Not relevant.}, } @article {pmid40406897, year = {2025}, author = {Li, J and Zi, X and Fang, J and Liang, M and Ju, M and Sun, Z and Shen, B and Zhang, X}, title = {Endoplasmic Reticulum Stress Induces Liquid-Liquid Phase Separation of GRP78 and Modulates Protein Aggregation Dynamics.}, journal = {ACS sensors}, volume = {10}, number = {6}, pages = {4535-4543}, doi = {10.1021/acssensors.5c00807}, pmid = {40406897}, issn = {2379-3694}, mesh = {Endoplasmic Reticulum Chaperone BiP ; Humans ; *Endoplasmic Reticulum Stress ; *Protein Aggregates ; Superoxide Dismutase-1/metabolism/chemistry/genetics ; *Heat-Shock Proteins/metabolism/chemistry ; Fluorescent Dyes/chemistry/chemical synthesis ; Phase Separation ; }, abstract = {Abnormal protein aggregation is a hallmark of neurodegenerative diseases, disrupting cellular homeostasis. Glucose-regulated protein 78 (GRP78), a key endoplasmic reticulum (ER) chaperone, plays a crucial role in protein folding and the ER stress response. Recent studies suggest that GRP78 undergoes liquid-liquid phase separation (LLPS) to form dynamic condensates; however, its functional implications under pathological conditions remain unclear. In this study, we designed and synthesized two fluorescent probes (ER-Pro and Agg-Pro) for specifically labeling GRP78 and monitoring microenvironmental polarity changes during protein phase transition. By integrating fluorescence lifetime imaging microscopy and confocal microscopy, we demonstrated that GRP78 undergoes LLPS under ER stress and recruits the amyotrophic lateral sclerosis-associated mutant protein SOD1(A4V), influencing its aggregation dynamics. Further investigations revealed that SOD1(A4V) aggregation is accompanied by local polarity changes, highlighting a potential role for GRP78 LLPS in protein quality control. Our findings provide new insights into ER homeostasis regulation and the pathogenesis of neurodegenerative diseases, offering potential strategies for early diagnosis and therapeutic intervention.}, } @article {pmid40406043, year = {2025}, author = {Wang, L and Ma, L and Gao, Z and Wang, Y and Qiu, J}, title = {Significance of gene therapy in neurodegenerative diseases.}, journal = {Frontiers in neuroscience}, volume = {19}, number = {}, pages = {1515255}, pmid = {40406043}, issn = {1662-4548}, abstract = {Gene therapy is an approach that employs vectors to deliver genetic material to target cells, aiming to correct genes with pathogenic mutations and modulate one or more genes responsible for disease progression. It holds significant value for clinical applications and offers broad market potential due to the large patient population affected by various conditions. For instance, in 2023, the Food and Drug Administration (FDA) approved 55 new drugs, including five specifically for gene therapy targeting hematologic and rare diseases. Recently, with advancements in understanding the pathogenesis and development of neurodegenerative diseases (NDDs), gene therapy has emerged as a promising avenue for treating Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), and spinal muscular atrophy (SMA), particularly in personalized medicine. Notably, the FDA has approved three clinical applications for combating SMA, utilizing viral vectors delivered via intravenous and intrathecal injections. However, gene therapy for other NDDs remains in clinical trials, necessitating improvements in viral vectors, exploration of new vectors, optimization of delivery routes, and further investigation into pathogenesis to identify novel targets. This review discusses recent advancements in gene therapy for NDDs, offering insights into developing new therapeutic strategies.}, } @article {pmid40405710, year = {2025}, author = {Clift, A and Rowen, D and Knox, L and Griffiths, AW and McDermott, CJ}, title = {A Systematic Review of Attributes Influencing Preferences for Treatments and Interventions in People With Amyotrophic Lateral Sclerosis (ALS).}, journal = {Muscle & nerve}, volume = {72}, number = {3}, pages = {359-382}, pmid = {40405710}, issn = {1097-4598}, support = {//National Institute for Health and Care Research/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy/psychology ; *Patient Preference/psychology ; Quality of Life/psychology ; Patient-Centered Care ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that has no cure, and treatments predominantly focus on improving quality of life. Patient-centred care is central to bringing about meaningful improvements to quality of life. This review addresses the lack of consolidated evidence on what matters most to people with ALS (pwALS) by synthesizing 44 preference-based studies covering six different treatment and intervention categories. Data-based convergent synthesis identified five overarching factors influencing preferences: ease of use, accessibility, making life easier, autonomy, and safety/reliability. Simplifying and enhancing accessibility of treatment delivery across disease stages aligns with the nature of neurodegenerative disorders such as ALS, where function declines as the disease progresses. The value in perceived and real control reflects the profound impact ALS has on an individual's independence. Safety and reliability are crucial for people with ALS and are recognized as fundamental requirements for quality healthcare. The themes identified in this review can inform the attributes of preference elicitation methods. Systematically varying the levels of these attributes elicits quantitative measures of preferences. These findings can be used to inform and develop healthcare policy and clinical practice in ALS care. Specifically, preferences related to drug treatments can then be integrated into target product profiles (TPPs) to align drug development with the needs and values of pwALS. Integrating patient preferences into clinical practice promotes patient-centred care, increasing both patient satisfaction and treatment effectiveness.}, } @article {pmid40405476, year = {2025}, author = {Ma, C and Tian, G and Liu, Y and Wang, P and Meng, C and Liu, J and Guo, S and Qi, D}, title = {Highly Stretchable and Conductive Wrapping-Entanglement Coupling Network for All-Carbon-Based Soft Bioelectrode.}, journal = {Nano letters}, volume = {25}, number = {22}, pages = {9061-9069}, doi = {10.1021/acs.nanolett.5c01522}, pmid = {40405476}, issn = {1530-6992}, mesh = {*Carbon/chemistry ; Animals ; Electric Conductivity ; Rats ; Magnetic Resonance Imaging ; Electrodes ; Electromyography/instrumentation ; Polymers/chemistry ; Electrocardiography ; *Nanostructures/chemistry ; }, abstract = {Carbon-based materials are ideal for MRI-compatible bioelectrodes, essential for monitoring electromyographic signals and delivering electrical stimulation in diseases like ALS and MG. However, conventional stretchable carbon electrodes struggle with balancing electrical and mechanical properties. This paper proposes a new method of using a wrapping-entanglement coupling carbon network with multiple carbon nanomaterials in a polymer matrix, achieving high conductivity (454.5 S/m, several to dozens of times higher than that of electrodes made from other carbon materials embedded in polymers) and exceptional elongation at break (>3000%, carbon-based stretchable electrodes typically have a stretch rate of <500%). This electrode demonstrates remarkable durability, withstanding over 10,000 cycles at 20% strain (carbon-based stretchable electrodes can typically withstand <2500 cycles), outperforming existing carbon-polymer electrodes. It can be conformally attached to the skin and used as multichannel electrodes for ECG and EMG monitoring, matching the performance of Ag/AgCl electrodes. Implanted in rat models, it successfully recorded electrophysiological signals while reducing MRI artifacts compared to Pt electrodes in a 9.4 T MRI scanner. This innovation offers significant potential for advanced medical diagnostics and treatments.}, } @article {pmid40405223, year = {2025}, author = {Yoonesi, S and Abedi Azar, R and Arab Bafrani, M and Yaghmayee, S and Shahavand, H and Mirmazloumi, M and Moazeni Limoudehi, N and Rahmani, M and Hasany, S and Idjadi, FZ and Aalipour, MA and Gharedaghi, H and Salehi, S and Asadi Anar, M and Soleimani, MS}, title = {Facial expression deep learning algorithms in the detection of neurological disorders: a systematic review and meta-analysis.}, journal = {Biomedical engineering online}, volume = {24}, number = {1}, pages = {64}, pmid = {40405223}, issn = {1475-925X}, mesh = {Humans ; *Deep Learning ; *Facial Expression ; *Nervous System Diseases/diagnosis ; }, abstract = {BACKGROUND: Neurological disorders, ranging from common conditions like Alzheimer's disease that is a progressive neurodegenerative disorder and remains the most common cause of dementia worldwide to rare disorders such as Angelman syndrome, impose a significant global health burden. Altered facial expressions are a common symptom across these disorders, potentially serving as a diagnostic indicator. Deep learning algorithms, especially convolutional neural networks (CNNs), have shown promise in detecting these facial expression changes, aiding in diagnosing and monitoring neurological conditions.

OBJECTIVES: This systematic review and meta-analysis aimed to evaluate the performance of deep learning algorithms in detecting facial expression changes for diagnosing neurological disorders.

METHODS: Following PRISMA2020 guidelines, we systematically searched PubMed, Scopus, and Web of Science for studies published up to August 2024. Data from 28 studies were extracted, and the quality was assessed using the JBI checklist. A meta-analysis was performed to calculate pooled accuracy estimates. Subgroup analyses were conducted based on neurological disorders, and heterogeneity was evaluated using the I[2] statistic.

RESULTS: The meta-analysis included 24 studies from 2019 to 2024, with neurological conditions such as dementia, Bell's palsy, ALS, and Parkinson's disease assessed. The overall pooled accuracy was 89.25% (95% CI 88.75-89.73%). High accuracy was found for dementia (99%) and Bell's palsy (93.7%), while conditions such as ALS and stroke had lower accuracy (73.2%).

CONCLUSIONS: Deep learning models, particularly CNNs, show strong potential in detecting facial expression changes for neurological disorders. However, further work is needed to standardize data sets and improve model robustness for motor-related conditions.}, } @article {pmid40404809, year = {2025}, author = {Morando, MA and D'Alessandro, V and Spinello, A and Sollazzo, M and Monaca, E and Sabbatella, R and Volpe, MC and Gervaso, F and Polini, A and Mizielinska, S and Alfano, C}, title = {Epigallocatechin-3-gallate binds tandem RNA recognition motifs of TDP-43 and inhibits its aggregation.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {17879}, pmid = {40404809}, issn = {2045-2322}, support = {CUP F85F20000260006//Programma Operativo Nazionale Ricerca e Innovazione 2014-2020 (CCI 2014IT16M2OP005), Fondo Sociale Europeo, Azione I.1 "Dottorati Innovativi con caratterizzazione Industriale"/ ; CUP B73C21001300006//Italian Ministry of University and Research/ ; }, mesh = {*Catechin/analogs & derivatives/pharmacology/chemistry/metabolism ; *DNA-Binding Proteins/metabolism/chemistry ; Humans ; Protein Binding ; *Protein Aggregates/drug effects ; *RNA Recognition Motif ; Amyotrophic Lateral Sclerosis/metabolism ; }, abstract = {Transactive response DNA-binding Protein 43 (TDP-43) aggregation is a key pathological feature in Amyotrophic Lateral Sclerosis and related neurodegenerative diseases. This study investigates the inhibitory effects of Epigallocatechin-3-gallate (EGCG), a polyphenol found in green tea, on TDP-43 aggregation. Using a combination of fluorescence assays, NMR spectroscopy, and computational modeling, we demonstrate that Epigallocatechin-3-gallate significantly delays the nucleation phase of TDP-43 aggregation process, thus inhibiting the formation of TDP-43 aggregates in vitro. Additionally, we proved a direct interaction of the compound with the RNA recognition motifs of TDP-43 and modeled the mechanism of interaction. Our findings reveal that EGCG stabilizes the RRM domains, counteracting aggregation by interfering with the early stages of the amyloidogenic pathway. Furthermore, EGCG's stability under experimental conditions was ensured using reducing agents, highlighting the importance of maintaining its reduced form for reproducible results. These insights underscore the therapeutic potential of EGCG in TDP-43 proteinopathies and provide a foundation for developing targeted treatments for ALS and related disorders.}, } @article {pmid40403957, year = {2025}, author = {Zeng, L and Yang, J and Zhang, C and Zhu, J and Zhong, S and Liu, X and Xie, H and Wang, L and Chen, L and Zhong, M and Hua, F and Liang, W}, title = {Miro1: A potential target for treating neurological disorders.}, journal = {Neuroscience}, volume = {577}, number = {}, pages = {228-239}, doi = {10.1016/j.neuroscience.2025.05.019}, pmid = {40403957}, issn = {1873-7544}, mesh = {Humans ; Animals ; *rho GTP-Binding Proteins/metabolism ; *Nervous System Diseases/metabolism/drug therapy ; *Mitochondria/metabolism ; *Mitochondrial Proteins/metabolism ; Neurons/metabolism ; }, abstract = {The Miro1 protein is a member of the mitochondrial Rho GTPase (Miro) protein family and plays a crucial role in regulating the dynamic processes of mitochondria and participating in cellular movement and mitochondrial transport. In the nervous system, it ensures adequate energy supply for normal neuronal function and synaptic transmission. Additionally, Miro1 actively participates in the regulation of mitochondrial quality control and stress responses within neurons. Its primary function is to sense intracellular stress signals to regulate mitochondrial movement and metabolism, thereby adapting to environmental changes. Multiple studies have indicated that the Miro1 protein is associated with the pathogenesis of various neurological disorders, such as Alzheimer's Disease(AD), Parkinson's Disease(PD), and Amyotrophic Lateral Sclerosis(ALS). This article reviews the mechanistic role of Miro1 in these diseases and summarizes the latest research on its involvement in neurological disorders. These efforts aim to provide unified treatment strategies for certain neurological disorders and explore the potential for treating complex neurological diseases.}, } @article {pmid40403623, year = {2025}, author = {Chtourou, M and Osuna, MD and Vázquez-García, JG and De Prado, R and Lozano-Juste, J and Marín, GM and Hada, Z and Souissi, T and Torra, J}, title = {Several point mutations and metabolism confer cross-resistance to ALS-inhibiting herbicides in Tunisian wild mustard.}, journal = {Plant physiology and biochemistry : PPB}, volume = {225}, number = {}, pages = {110043}, doi = {10.1016/j.plaphy.2025.110043}, pmid = {40403623}, issn = {1873-2690}, mesh = {*Acetolactate Synthase/antagonists & inhibitors/genetics/metabolism ; *Herbicides/pharmacology ; *Herbicide Resistance/genetics ; Tunisia ; *Point Mutation/genetics ; *Sinapis/genetics/drug effects/metabolism/enzymology ; *Plant Proteins/genetics/metabolism/antagonists & inhibitors ; }, abstract = {A growing number of weed biotypes showing resistance to acetolactate synthase (ALS)-inhibitors have been reported in several species, notably including Sinapis arvensis L. Two putative resistant (R) populations of S. arvensis from Tunisia were subjected to greenhouse and laboratory investigations to validate resistance to ALS-inhibitors and to determinate the mechanisms involved. The results indicated that both populations were resistant to four distinct ALS-inhibiting herbicides, tribenuron-methyl (TM), florasulam, flucarbazone and imazamox (IMZ), thereby confirming cross-resistance between them. The dose of (TM) required to achieve a 50 % reduction in plant growth (ED50) and 50 % mortality (LC50) in R populations of S. arvensis was found to be at least 60 times greater than the recommended field dose (18.7 g ai ha[-1]) applied in cereal crops in Tunisia, indicating a significantly elevated resistance factor. Synergist experiments using malathion as a cytochrome P450 (Cyt-P450) inhibitor demonstrated a reduction in resistance to imazamox (IMZ) in both resistant (R) biotypes, indicating that Cyt-P450 plays a partial role in the resistance mechanism. In addition, ALS gene analysis identified three key point mutations, Pro197Ala, Asp376Glu and Trp574Leu, in both R populations. The docking analysis demonstrated that Asp376Glu mutation in S. arvensis could confer cross-resistance to IMZ and TM herbicides. CAPS and dCAPS methods were developed for detecting the Trp574Leu and Asp376Glu mutations, respectively, in S arvensis and it was shown that work efficiently. Fortunately, the study also confirmed that 2,4-D still effectively controlled S. arvensis populations. This study provides valuable insights into the mechanisms underlying herbicide resistance in S.arvensis populations from Tunisia, demonstrating that both target-site resistance (TSR) and non-target-site resistance (NTSR) contribute to the species' broad-spectrum resistance against four dissimilar ALS-inhibitors.}, } @article {pmid40403503, year = {2025}, author = {Dhapola, R and Paidlewar, M and Kumari, S and Sharma, P and Vellingiri, B and Medhi, B and HariKrishnaReddy, D}, title = {cGAS-STING and neurodegenerative diseases: A molecular crosstalk and therapeutic perspective.}, journal = {International immunopharmacology}, volume = {159}, number = {}, pages = {114902}, doi = {10.1016/j.intimp.2025.114902}, pmid = {40403503}, issn = {1878-1705}, mesh = {Humans ; *Nucleotidyltransferases/metabolism ; *Neurodegenerative Diseases/drug therapy/metabolism/immunology ; *Membrane Proteins/metabolism ; Animals ; Signal Transduction ; }, abstract = {Neurodegenerative disorders such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), Amyotrophic Lateral Sclerosis (ALS), Multiple Sclerosis (MS) and Frontotemporal Dementia (FTD) share key pathological features, including neuroinflammation, oxidative stress, mitochondrial dysfunction, autophagic dysfunction, and DNA damage. By identifying cytosolic DNA and triggering the type I interferon response, the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway regulates neuroinflammation. Dysregulated cGAS-STING signaling has been linked to neuroinflammation and neuronal degeneration across multiple neurodegenerative conditions. In many neurodegenerative disorders, neuroinflammation is mediated by the cGAS-STING pathway. Mitochondrial malfunction and impaired autophagy cause cytosolic DNA buildup in Huntington's, Parkinson's, and Alzheimer's diseases, which activates cGAS-STING and drives chronic inflammation. This pathway is triggered by TDP-43 pathology and nucleic acid dysregulation in ALS and FTD, which leads to neuronal destruction. Both central demyelination and peripheral immunological responses are linked to cGAS-STING activation in multiple sclerosis. Various inhibitors, such as RU.521, H-151, and naturally occurring compounds like metformin, potentially attenuate cGAS-STING-mediated neuroinflammation and associated pathologies. H-151 significantly decreased the expression of pro-inflammatory markers in murine macrophage J774 cells activated with cGAMP: TNF-α by 68 %, IFN-β by 84 %, and CXCL10 by 96 %. cGAS-STING inhibitors target neuroinflammation, offering a disease-modifying approach unlike current symptomatic treatments. However, challenges like blood-brain barrier penetration, off-target effects, and immune suppression hinder clinical translation, necessitating optimized drug delivery and immune modulation. With a focus on its potential for future clinical applications, this review explores the role of the cGAS-STING pathway in neurodegeneration and new treatment approaches.}, } @article {pmid40401739, year = {2025}, author = {Perera, ND and De Silva, S and Tomas, D and Cuic, B and Turner, BJ}, title = {Mapping Glial Autophagy Dynamics in an Amyotrophic Lateral Sclerosis Mouse Model Reveals Microglia and Astrocyte Autophagy Dysfunction.}, journal = {Glia}, volume = {73}, number = {9}, pages = {1860-1882}, pmid = {40401739}, issn = {1098-1136}, support = {IG 2132//Motor Neurone Disease Research Australia/ ; 2020-2024//Stafford Fox Medical Research Foundation/ ; Early Career Researcher Grant 2020//University of Melbourne/ ; ID 2202//Bethlehem Griffiths Research Foundation Grant 2022/ ; }, mesh = {Animals ; *Amyotrophic Lateral Sclerosis/pathology/metabolism/genetics ; *Autophagy/physiology ; *Astrocytes/pathology/metabolism ; Mice ; *Microglia/pathology/metabolism ; Mice, Transgenic ; Disease Models, Animal ; Superoxide Dismutase-1/genetics/metabolism ; *Neuroglia/pathology/metabolism ; Spinal Cord/pathology ; Motor Neurons/pathology ; Mice, Inbred C57BL ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is defined by motor neuron death. However, recent research has identified non-cell-autonomous mechanisms, with significant involvement of glia in disease progression. We link previous observations of intracellular protein aggregates in glia to the autophagy pathway, the primary mediator of intracellular degradation of large protein aggregates. While dysfunctional autophagy is reported in ALS motor neurons, pre-clinical and clinical outcomes of autophagy modulators have been inconsistent, indicating the need for a nuanced understanding of autophagy dynamics across CNS cell types and ALS-affected regions. We hypothesized that glial autophagy is defective in ALS, with glial-type-specific dysfunction. To investigate in vivo autophagy dynamics, we intercrossed SOD1[G93A] mice with transgenic RFP-EGFP-LC3 autophagy reporter mice, enabling the quantification of autophagy degradation, termed flux. Investigation of autophagy dynamics in SOD1 oligodendrocytes, microglia, and astrocytes at key disease stages uncovered useful insights. While oligodendrocytes seemed to mount effective compensatory autophagic responses to combat mutant SOD1, significantly increased autophagy flux was observed in symptomatic spinal microglia and astrocytes in comparison to controls. Symptomatic SOD1 astrocytes displayed greater autophagy dysfunction compared to microglia, with subcellular analysis revealing cell compartment-specific, transient autophagy defects that returned to control levels by end stage. Interestingly, spinal glia showed more pronounced and earlier autophagy dysfunction compared to motor cortex glia, where autophagy dysfunction emerged later in disease end stage, aligning with greater spinal cord pathology reported in this model. Our results suggest that cell-type- and time-specific targeting might be essential when developing autophagy therapeutics for ALS, with prioritization of astrocytic autophagy modulation.}, } @article {pmid40401027, year = {2025}, author = {Libonati, L and Cambieri, C and Ceccanti, M and Moret, F and Di Giulio, M and Palma, E and Inghilleri, M}, title = {Twitch force in human Amyotrophic Lateral Sclerosis.}, journal = {Frontiers in neurology}, volume = {16}, number = {}, pages = {1590950}, pmid = {40401027}, issn = {1664-2295}, abstract = {INTRODUCTION: This study investigated differences in muscle twitch force between slow and fast progressors of amyotrophic lateral sclerosis (ALS) to better understand disease heterogeneity and identify potential biomarkers of disease progression.

METHODS: Forty-four ALS patients were classified as slow or fast progressors based on disease progression rates. Electrophysiological assessments, including compound muscle action potential (CMAP) and muscle force measurements, were conducted. Creatine kinase (CK) levels were also evaluated.

RESULTS: Slow progressors demonstrated significantly higher muscle peak force and area under the curve (AUC) compared to fast progressors, reflecting greater muscle strength and endurance. CK levels were also elevated in slow progressors.

DISCUSSION: Despite similar CMAp values, slow progressors retained greater muscle strength, possibly due to a reduced degeneration of fast-twitch fibers and compensatory axonal sprouting. These adaptations may preserve muscle function and elevate CK levels, suggesting better muscle integrity in slow progressors.

CONCLUSION: Muscle function profiles and CK levels are promising indicators of ALS progression. These findings could enhance early detection of disease progression and lead to targeted interventions to preserve muscle function. Further research is needed to validate these results and explore the underlying functional mechanisms of disease heterogeneity.}, } @article {pmid40400898, year = {2025}, author = {Aziz, S and Anbreen, S and Shahzad, S and Ahmed, MS and Sharma, V and Yang, J and Ali, L}, title = {Investigating nanoparticle's utilization in stem cell therapy for neurological disorders.}, journal = {American journal of stem cells}, volume = {14}, number = {1}, pages = {1-13}, pmid = {40400898}, issn = {2160-4150}, abstract = {Stem cell therapy is a promising area of regenerative medicine, offering potential treatments for various life-threatening disorders. Stem cells are classified based on their differentiation potential into totipotent, pluripotent, and multipotent stem cells. Among them, mesenchymal stem cells (MSCs) are widely used in regenerative medicine due to their tissue regeneration capabilities and ability to differentiate into multiple cell types. Stem cells are being explored for treating neurodegenerative disorders like Parkinson's, Alzheimer's, Huntington's, and amyotrophic lateral sclerosis (ALS). These conditions result from progressive neuronal degeneration, leading to irreversible damage. Challenges such as cell survival, immune rejection, tumor formation, and ethical concerns related to embryonic stem cells need to be addressed. Nanotechnology is emerging as a tool for enhancing stem cell therapy, improving targeted delivery and effectiveness. Nanoparticles possess the ability to create microenvironments as substrates, facilitate targeted administration, and enable real-time, precise imaging of stem cells. This review explores the integration of stem cells and nanotechnology as regenerative medicine tool for neurodegenerative disease treatment, analyzing current strategies and therapeutic approaches. Integrating nanotechnology with stem cell therapy may significantly improve targeted delivery and enhance regenerative outcomes for neurodegenerative disorders.}, } @article {pmid40400199, year = {2025}, author = {Ramgopal, S and Callaway, CW and Martin-Gill, C and Okubo, M}, title = {Using Life-Saving Interventions to Determine Optimal Vital Sign Ranges among Adults Encountered by Emergency Medical Services.}, journal = {Prehospital and disaster medicine}, volume = {40}, number = {3}, pages = {129-135}, doi = {10.1017/S1049023X25001542}, pmid = {40400199}, issn = {1945-1938}, mesh = {Humans ; Retrospective Studies ; *Emergency Medical Services ; *Vital Signs ; Male ; Female ; Adult ; Middle Aged ; Aged ; }, abstract = {BACKGROUND: Vital signs are an essential component of the prehospital assessment of patients encountered in an emergency response system and during mass-casualty disaster events. Limited data exist to define meaningful vital sign ranges to predict need for advanced care.

STUDY OBJECTIVES: The aim of this study was to identify vital sign ranges that were maximally predictive of requiring a life-saving intervention (LSI) among adults cared for by Emergency Medical Services (EMS).

METHODS: A retrospective study of adult prehospital encounters that resulted in hospital transport by an Advanced Life Support (ALS) provider in the 2022 National EMS Information System (NEMSIS) dataset was performed. The outcome was performance of an LSI, a composite measure incorporating critical airway, medication, and procedural interventions, categorized into eleven groups: tachydysrhythmia, cardiac arrest, airway, seizure/sedation, toxicologic, bradycardia, airway foreign body removal, vasoactive medication, hemorrhage control, needle decompression, and hypoglycemia. Cut point selection was performed in a training partition (75%) to identify ranges for heart rate (HR), respiratory rate (RR), systolic blood pressure (SBP), oxygen saturation, and Glasgow Coma Scale (GCS) by using an approach intended to prioritize specificity, keeping sensitivity constrained to at least 25%.

RESULTS: Of 18,259,766 included encounters (median age 63 years; 51.8% male), 6.3% had at least one LSI, with the most common being airway interventions (2.2%). Optimal ranges for vital signs included 47-129 beats/minute for HR, 8-30 breaths/minute for RR, 96-180mmHg for SBP, >93% for oxygen saturation, and >13 for GCS. In the test partition, an abnormal vital sign had a sensitivity of 75.1%, specificity of 66.6%, and positive predictive value (PPV) of 12.5%. A multivariable model encompassing all vital signs demonstrated an area under the receiver operator characteristic curve (AUROC) of 0.78 (95% confidence interval [CI], 0.78-0.78). Vital signs were of greater accuracy (AUROC) in identifying encounters needing airway management (0.85), needle decompression (0.84), and tachydysrhythmia (0.84) and were lower for hemorrhage control (0.52), hypoglycemia management (0.68), and foreign body removal (0.69).

CONCLUSION: Optimal ranges for adult vital signs in the prehospital setting were statistically derived. These may be useful in prehospital protocols and medical alert systems or may be incorporated within prediction models to identify those with critical illness and/or injury for patients with out-of-hospital emergencies.}, } @article {pmid40400037, year = {2025}, author = {Harjuhaahto, S and Jokela, M and Rajendran, J and Rokka, M and Hu, B and Kvist, J and Zhang, F and Zárybnický, T and Haimilahti, K and Euro, L and Pirinen, E and Huber, N and Herukka, SK and Haapasalo, A and Kuuluvainen, E and Gopalakrishnan, S and Katajisto, P and Hietakangas, V and Burg, T and Van Den Bosch, L and Huang, X and Narendra, DP and Kuure, S and Ylikallio, E and Tyynismaa, H}, title = {Dose-dependent CHCHD10 dysregulation dictates motor neuron disease severity and alters creatine metabolism.}, journal = {Acta neuropathologica communications}, volume = {13}, number = {1}, pages = {111}, pmid = {40400037}, issn = {2051-5960}, mesh = {Animals ; Humans ; Mice ; *Mitochondrial Proteins/genetics/metabolism ; *Creatine/metabolism ; Male ; Motor Neurons/metabolism ; Female ; Disease Models, Animal ; *Motor Neuron Disease/genetics/metabolism ; Energy Metabolism/genetics ; Mice, Transgenic ; Mutation ; Muscular Atrophy, Spinal/genetics/metabolism ; }, abstract = {Dominant defects in CHCHD10, a mitochondrial intermembrane space protein, lead to a range of neurological and muscle disease phenotypes including amyotrophic lateral sclerosis. Many patients present with spinal muscular atrophy Jokela type (SMAJ), which is caused by heterozygous p.G66V variant. While most disease variants lead to aggregation of CHCHD10 and activation of proteotoxic stress responses, the pathogenic mechanisms of the p.G66V variant are less clear. Here we report the first homozygous CHCHD10 patient, and show that the variant dosage dictates the severity of the motor neuron disease in SMAJ. We demonstrate that the amount of the mutant CHCHD10 is reduced, but the disease mechanism of p.G66V is not full haploinsufficiency as residual mutant CHCHD10 protein is present even in a homozygous state. Novel knock-in mouse model recapitulates the dose-dependent reduction of mutant CHCHD10 protein and the slow disease progression of SMAJ. With metabolome analysis of patients' primary fibroblasts and patient-specific motor neurons, we show that CHCHD10 p.G66V dysregulates energy metabolism, leading to altered redox balance and energy buffering by creatine metabolism.}, } @article {pmid40399998, year = {2025}, author = {Xu, L and Wang, Y and Li, X and Hu, Q and Adamkova, V and Xu, J and Harris, CJ and Ausin, I}, title = {H3K4me3 binding ALFIN-LIKE proteins recruit SWR1 for gene-body deposition of H2A.Z.}, journal = {Genome biology}, volume = {26}, number = {1}, pages = {137}, pmid = {40399998}, issn = {1474-760X}, support = {URF\R1\201016//Royal Society, UK/ ; URF\R1\201016//Royal Society, UK/ ; URF\R1\201016//Royal Society, UK/ ; EP/X025306/1/ERC_/European Research Council/International ; EP/X025306/1/ERC_/European Research Council/International ; EP/X025306/1/ERC_/European Research Council/International ; 321703059 and 32370580//National Science Foundation of China/ ; 321703059 and 32370580//National Science Foundation of China/ ; 321703059 and 32370580//National Science Foundation of China/ ; 321703059 and 32370580//National Science Foundation of China/ ; 321703059 and 32370580//National Science Foundation of China/ ; }, mesh = {*Histones/metabolism/genetics ; *Arabidopsis Proteins/metabolism/genetics ; *Arabidopsis/genetics/metabolism ; Gene Expression Regulation, Plant ; Protein Binding ; *Adenosine Triphosphatases/metabolism ; }, abstract = {BACKGROUND: The H2A.Z histone variant is highly enriched over gene bodies, playing an essential role in several genome-templated processes, including transcriptional regulation and epigenetic patterning across eukaryotes. Deposition of H2A.Z is mediated by the SWR1 remodeling complex. How SWR1 is directed to gene bodies is largely unknown.

RESULTS: Here, we show that ALFIN-LIKE (AL) proteins are responsible for H2A.Z gene body patterning in Arabidopsis. AL proteins encode H3K4me3-binding PHD domains, and by ChIP-seq, we confirm preferential binding of AL5 to H3K4me3 over H3K4me1/2 in planta. We observe a global reduction in H2A.Z in al septuple mutants (al7m), especially over H3K4me3-enriched genic regions. While MBD9 recruits SWR1 to nucleosome-free regions, ALs act non-redundantly with MBD9 for deposition of H2A.Z. Notably, al7m mutants show severe developmental abnormalities and upregulation of H2A.Z gene body-enriched responsive genes.

CONCLUSIONS: Therefore, we propose a model whereby AL proteins direct gene body enrichment of H2A.Z by recruiting SWR1 to H3K4me3-containing responsive genes.}, } @article {pmid40399476, year = {2025}, author = {Rasà, DM and Stoppa, I and Bérenger-Currias, N and Pasho, E and Ciura, S and Kabashi, E and Martinat, C and Boido, M}, title = {Stress exposure affects amyotrophic lateral sclerosis pathogenesis via PI3K/Akt and focal adhesion pathways: evidence from three experimental models.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {17583}, pmid = {40399476}, issn = {2045-2322}, mesh = {Animals ; *Amyotrophic Lateral Sclerosis/metabolism/pathology/genetics/etiology ; *Proto-Oncogene Proteins c-akt/metabolism ; *Phosphatidylinositol 3-Kinases/metabolism ; Disease Models, Animal ; Mice ; Humans ; *Focal Adhesions/metabolism ; *Signal Transduction ; Male ; Superoxide Dismutase-1/genetics/metabolism ; Female ; Motor Neurons/metabolism/pathology ; Mice, Transgenic ; *Stress, Physiological ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a multifactorial motor neuron (MN) disease, characterized by several cellular dysfunctions, many of which are shared by different neurodegenerative diseases. Here, we investigated whether a stressful lifestyle might exacerbate the altered mechanisms and affect the disease progression in ALS-predisposed conditions. To model stress in vivo, SOD1[G93A] mice underwent a chronic unpredicted mild stress protocol. This resulted in a significant impairment in body weight gain and motor performance, in a gender-specific manner. Moreover, the gene expression of Col1a1, Col1a2 and Il6 was strongly dysregulated in motor cortex and/or spinal cord of stressed mice. To assess the direct impact of stress on MNs, NSC-34 hSOD1[G93A] cells underwent oxygen and glucose deprivation. Compared to NSC-34 hSOD1[WT], mutated MNs exhibited a reduced capacity to cope with stress. By performing gene expression, protein-protein interaction, gene ontology and pathway enrichment analyses, we also revealed the pivotal role of the PI3K/Akt and focal adhesion pathways (triggered by Gsk3b, Il6, Igf1 and/or collagen) in mediating stress response. Similar results were observed in stressed human iPSCs-derived TARDBP[G298S] MNs. In conclusion, our results suggest that the PI3K/Akt and focal adhesion pathways play a crucial role in stress response across different ALS-predisposed models: the study paves the way for novel therapeutic targets and highlights the relevance of a healthy lifestyle.}, } @article {pmid40398193, year = {2025}, author = {Carra, S and Fabian, B and Taghavi, H and Milanetti, E and Giliberti, V and Ruocco, G and Shepherd, J and Vendruscolo, M and Fuxreiter, M}, title = {Virus-like particles of retroviral origin in protein aggregation and neurodegenerative diseases.}, journal = {Molecular aspects of medicine}, volume = {103}, number = {}, pages = {101369}, doi = {10.1016/j.mam.2025.101369}, pmid = {40398193}, issn = {1872-9452}, mesh = {Humans ; *Neurodegenerative Diseases/metabolism/virology/pathology ; *Protein Aggregates ; *Endogenous Retroviruses/metabolism/genetics ; *Protein Aggregation, Pathological/metabolism/virology ; Animals ; *Virion/metabolism ; Protein Folding ; }, abstract = {A wide range of human diseases are associated with protein misfolding and amyloid aggregates. Recent studies suggest that in certain neurological disorders, including Amyotrophic Lateral Sclerosis (ALS), Frontotemporal Dementia (FTD) and various tauopathies, protein aggregation may be promoted by virus-like particles (VLPs) formed by endogenous retroviruses (ERVs). The molecular mechanisms by which these VLPs contribute to protein aggregation, however, remain enigmatic. Here, we discuss possible molecular mechanisms of ERV-derived VLPs in the formation and spread of protein aggregates. An intriguing possibility is that liquid-like condensates may facilitate the formation of both protein aggregates and ERV-derived VLPs. We also describe how RNA chaperoning, and the encapsulation and trafficking of misfolded proteins, may contribute to protein homeostasis through the elimination of protein aggregates from cells. Based on these insights, we discuss future potential therapeutic opportunities.}, } @article {pmid40398050, year = {2025}, author = {Hirschbeck, SS and Sawaya, MR and Lindberg, ET and Limbach, MN and Jang, JH and Lazar Cantrell, KL and Eisenberg, DS and Do, TD}, title = {Amyloid Oligomers: Expediting Crystal Growth and Revisiting the Corkscrew Structures.}, journal = {Journal of the American Chemical Society}, volume = {147}, number = {22}, pages = {18594-18605}, doi = {10.1021/jacs.5c00656}, pmid = {40398050}, issn = {1520-5126}, mesh = {*Superoxide Dismutase-1/chemistry/genetics ; Humans ; Crystallography, X-Ray ; *Amyloid/chemistry ; Models, Molecular ; Crystallization ; }, abstract = {Crystallizing soluble amyloid oligomers (AOs) presents a major challenge in studying disease-related mutations associated with amyloid diseases. The G37R mutation in superoxide dismutase 1 (SOD1) is linked to early onset amyotrophic lateral sclerosis (ALS), yet its toxic mechanism remains unclear. The transient nature and low solubility of AOs often complicate the production of high-quality crystals required for X-ray crystallography (XRC) analysis. To address these challenges, we employ native ion mobility spectrometry-mass spectrometry (IMS-MS) to screen SOD1 peptides and examine correlations between structural features that reflect AO stability, their sequence length, and specific mutations. In particular, previous studies showed that the P28K mutation in SOD1(28-38) enhances solubility, thus allowing the capture of AO corkscrew structures for both SOD1(28-38)[P28K] and SOD1(28-38)[P28K, G37R]. Building on these findings, we expanded our screening to include SOD1 peptides with longer sequences, identifying structural features in IMS-MS spectra that correlate with improved crystallization potential. This approach enabled us to distinguish the stabilizing effects of G37R from those of P28K, culminating in the successful determination of the first crystal structure of the SOD1 corkscrew containing the native proline.}, } @article {pmid40396445, year = {2025}, author = {Hu, X and Cheng, J and Yuan, R and Zhou, Y and Rao, J and Wan, Y and Li, Y and Zhang, X and Li, R}, title = {Gold nanoparticles: diagnostic and therapeutic applications in neurodegenerative disorders.}, journal = {Journal of drug targeting}, volume = {}, number = {}, pages = {1-18}, doi = {10.1080/1061186X.2025.2509287}, pmid = {40396445}, issn = {1029-2330}, abstract = {Neurodegenerative disorders (NDDs), including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and prion diseases, pose a significant and escalating health challenge in the context of an ageing population. Gold nanoparticles (GNPs) have emerged as promising agents in the diagnostic and therapeutic realms of NDDs, due to their unique ability to enhance drug delivery across the blood-brain barrier (BBB). This paper presents a comprehensive review of the application of GNPs in the context of NDDs diagnosis and therapy, highlighting their potential to transform patient management. Additionally, we systematically address the critical challenges associated with the use of GNPs in the treatment and diagnosis of NDDs, focusing on pharmacokinetics and metabolism, toxicity, long-term biocompatibility, regulatory challenges and cost-effectiveness. Furthermore, we synthesise ongoing clinical studies to provide a holistic perspective on the current state of research in this field. We also explore the prospective trajectories and clinical translational potential of GNPs, which may usher in a new era in the treatment of NDDs.}, } @article {pmid40396430, year = {2025}, author = {Yang, J and Xiao, F and Liu, Y and Bai, J and Tan, S}, title = {Nerve Conduction Study and the Prognosis of Amyotrophic Lateral Sclerosis: Exploration of Additional Neuroelectrophysiological Parameters.}, journal = {European journal of neurology}, volume = {32}, number = {5}, pages = {e70209}, pmid = {40396430}, issn = {1468-1331}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology/diagnosis/mortality ; *Neural Conduction/physiology ; Middle Aged ; Male ; Female ; Prognosis ; Aged ; Adult ; Action Potentials/physiology ; Aged, 80 and over ; Median Nerve/physiopathology ; Nerve Conduction Studies ; }, abstract = {OBJECTIVE: To investigate the correlation between nerve conduction study (NCS) parameters and the prognosis of patients with amyotrophic lateral sclerosis (ALS).

METHODS: NCS parameters were recorded from the median, ulnar, peroneal, tibial, and superficial peroneal nerves of 114 sporadic patients with ALS. The main endpoint was death or tracheostomy. Univariate Cox regression analysis was conducted for all the NCS parameters. Subsequently, multivariate analysis was performed using Cox stepwise regression, incorporating factors identified in the univariate analysis and known prognostic factors. Kaplan-Meier curves and log-rank tests were used for survival analysis. Receiver operating characteristic (ROC) curves were used to assess the predictive capabilities of NCS parameters.

RESULTS: The distal compound muscle action potential (dCMAP) negative peak area and the sensory nerve action potential (SNAP) amplitude of the median nerve were identified as prognostic factors for ALS. Further stratified analyses showed that larger median dCMAP negative peak area significantly correlated with better prognosis in elderly (> 61 years) patients with limb-onset ALS. Conversely, higher median SNAP amplitudes indicated worse prognosis in younger (≤ 61 years) patients with limb-onset ALS.

CONCLUSION: The current study showed that the dCMAP negative peak area and SNAP amplitude of the median nerve are independent prognostic factors for sporadic ALS patients.}, } @article {pmid40396429, year = {2025}, author = {Keipert, LM and Wurster, CD and Uzelac, Z and Dorst, J and Schuster, J and Wollinsky, K and Ludolph, A and Lulé, D}, title = {Pain in adult and adolescent patients with 5q-associated Spinal Muscular Atrophy - an often underrated phenomenon.}, journal = {Journal of neuromuscular diseases}, volume = {12}, number = {5}, pages = {662-669}, doi = {10.1177/22143602251325773}, pmid = {40396429}, issn = {2214-3602}, abstract = {BACKGROUND: Spinal muscular atrophy (SMA) is a genetic disorder leading to progressive muscle weakness and atrophy. Pain in SMA may be the consequence of the underlying neuromuscular disease but has hardly been investigated so far.

OBJECTIVE: To assess pain in SMA and its interaction with patient's wellbeing.

METHODS: In a prospective, cross-sectional study design, 70 adult and adolescent SMA patients (median age 30 years, IQR 21-49 years, types I-IV) were assessed at the Department of Neurology, Ulm University hospital. Pain was evaluated with a self-adapted Pain Scale, depressiveness with the ALS-Depression-Inventory-12-Items (ADI-12) and global Quality of Life (gQoL) with the Anamnestic Comparative Self-Assessment (ACSA).

RESULTS: We found an intermittent frequency of pain in 80% in SMA patients with more than half of the patients experience pain at least once a week. The mean pain intensity score estimated by pain frequency and strength was 24 on a scale of 0 to 240, indicating a frequently appearing mild to moderate pain. Pain was mostly located in the lumbar spine, hip, and thoracic spine. The pain intensity score was independent from demographics (age, gender) or clinical parameters (SMA type, physical state), but, instead, it was associated to depressiveness. Depressiveness was more prevalent in older SMA patients. gQoL was rather independent from pain intensity or physical state.

CONCLUSIONS: The study provides evidence for a prevalence of mild to moderate pain in 80% of adult and adolescent SMA patients. Pain was not simply caused by physical deficits and did not severely interfere with patients' quality of life, but, instead, was closely interrelated with patients' affective state.}, } @article {pmid40395983, year = {2025}, author = {Beckers, J and Van Damme, P}, title = {The role of autophagy in the pathogenesis and treatment of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD).}, journal = {Autophagy reports}, volume = {4}, number = {1}, pages = {2474796}, pmid = {40395983}, issn = {2769-4127}, abstract = {Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) represent two extremes of a neurodegenerative disease spectrum characterised by overlapping genetic, clinical, and neuropathological features. This review covers the intricate relationship between both ALS and FTD and defects in the autophagy and endolysosomal pathway as recent evidence has pointed towards alterations in these pathways as being a root cause of disease pathogenesis. Here, we review the current knowledge on the interplay between ALS/FTD and lysosomebased proteostasis pathways and carefully asses the steps of the autophagy and endolysosomal pathways that are impaired by ALS or FTDcausing variants. Finally, we present a comprehensive overview of therapeutic strategies aimed at restoring autophagic and lysosomal function as potential avenues for mitigating the impact of these devastating diseases. Through this review, we aim to enhance the understanding of the pathophysiological mechanisms involving autophagy and/or the endolysosomal system that underlie the ALS-FTD spectrum and underscore the necessity for specific therapeutic approaches that target these shared vulnerabilities.}, } @article {pmid40395632, year = {2025}, author = {Gerring, ZF and Bhalala, OG and Fearnley, LG and Oikari, LE and White, AR and Derks, EM and Watson, R and Yassi, N and Bahlo, M and Reay, WR}, title = {Drug repurposing candidates for amyotrophic lateral sclerosis using common and rare genetic variants.}, journal = {Brain communications}, volume = {7}, number = {3}, pages = {fcaf184}, pmid = {40395632}, issn = {2632-1297}, abstract = {Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative condition for which novel disease modifying therapies are urgently needed. Given the increasing bottlenecks in drug discovery pipelines, repurposing existing drugs for ALS may represent a path to expedite translation and improve disease outcomes. However, ALS is a heterogeneous disease for which the aetiology remains poorly characterized, complicating efforts to effectively repurpose drugs. We propose that the polygenic architecture of ALS genetic liability, which ranges from ultra-rare, high-impact variation to common frequency loci of small-individual effect, could be leveraged to prioritize drug repurposing candidates which are more generalizable to the ALS clinical population. Here, we utilize common and rare frequency ALS genetic risk with a novel approach to uncover therapeutic classes that may be prospective repurposing opportunities in ALS. The common variant-led analyses integrated both positional-based and functional gene-based tests on SNP-genotype data from a genome-wide association study of ALS and implicated mitogen-activated protein kinase signalling related downregulation through B-Raf inhibitors as a prospective target for repurposing. The rare variant-led approaches leveraged rare variant burden testing of exonic variation on whole genome-sequencing data from a subset of the common variant genome-wide association study cohort and prioritized B-vitamin related candidates, such as cobalamin and niacin. Clinical characterization of these putative repurposing opportunities revealed genetic support to existing biology for which related compounds are actively proceeding through ALS clinical studies. Moreover, leveraging transcriptomic data from ALS derived cell lines carrying a selection of pathogenic variants in genes that cause familial forms of ALS (C9orf72, SOD1, FUS and TARDBP) suggested that the action of B-Raf inhibitors may be of particular relevance to C9orf72 carriers, whilst the signal for B-vitamin signalling related targets was strongest in SOD1 carriers. In summary, we demonstrate the importance of considering the therapeutic actionability of both common and rare-variant mediated risk for ALS given the immense biological heterogeneity of this disorder. Future pre-clinical and clinical studies are now warranted to further characterize the tractability of these prioritized compounds.}, } @article {pmid40395537, year = {2024}, author = {Zhang, J and Pan, L}, title = {Mechanistic insights into the interaction between optineurin with RAB8A.}, journal = {Autophagy reports}, volume = {3}, number = {1}, pages = {2432848}, pmid = {40395537}, issn = {2769-4127}, abstract = {OPTN (optineurin), an amyotrophic lateral sclerosis (ALS)-associated modifier, plays vital roles in autophagy and cellular vesicular transport in mammals. OPTN can associate with RAB8A and the GTPase-activating protein TBC1D17, and facilitate the negative regulation of RAB8A by TBC1D17 (TBC domain family member 17). Recently, we reported the biochemical and structural characterizations of the interactions between OPTN, RAB8A and TBC1D17. We determined the crystal structure of the leucine-zipper domain (LZD) of OPTN with the GTP-bound active RAB8A and uncovered the molecular mechanism underpinning the specific interaction of OPTN with RAB8A. Moreover, we revealed that OPTN LZD and the TBC (Tre-2/Bub2/Cdc16) domain of TBC1D17 competitively bind to active RAB8A, while the central coiled-coil domain of OPTN and the active RAB8A can simultaneously interact with TBC1D17 TBC. In summary, our study provided mechanistic insights into the interaction of OPTN with RAB8A, and revealed the interaction relationship among OPTN, RAB8A and TBC1D17.}, } @article {pmid40395127, year = {2025}, author = {Ghannizadeh, M and Rustamzadeh, A and Homayoun, M and Aliakbari, Z and Zamani, S}, title = {Premotor cortex and frontal eye field region metabolite alteration in human amyotrophic lateral sclerosis patients: A quantitative survey.}, journal = {The neuroradiology journal}, volume = {}, number = {}, pages = {19714009251345102}, pmid = {40395127}, issn = {2385-1996}, abstract = {IntroductionAmyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by progressive upper and lower motor neuron degeneration, leading to muscle weakness, respiratory failure, and mortality. The premotor cortex (PMC), including the frontal eye field (FEF), shows greater resistance, with limb function declining earlier than eye movement. This study utilizes magnetic resonance spectroscopy (MRS) to investigate metabolite ratio changes in these regions for potential early ALS diagnosis.Methods and MaterialsFourteen ALS patients and healthy controls underwent MRS to assess neurometabolite levels, including N-acetyl aspartate (NAA), creatine (Cr), myo-inositol (mIns), and choline (Cho) in the PMC and FEF. ELISA measured superoxide dismutase-1 (SOD1) enzyme levels. Group differences were analyzed statistically using t-tests to evaluate significant variations.ResultIn ALS patients, a significant decrease in NAA/Cr (p = .045) and an increase in mIns/Cr (p < .0001) concentrations were observed in the PMC. No significant differences in Cho/Cr (p = .215) were detected between the FEF and PMC regions in ALS patients. Compared to the control group, NAA/Cr levels in the PMC and FEF regions of ALS patients were significantly lower (p = .004, .001), while mIns/Cr values were significantly higher (p = .001). However, no significant changes were observed in the Cho/Cr ratio in the FEF between ALS patients and controls. Additionally, SOD1 enzyme levels were significantly reduced in ALS patients (p < .0001).ConclusionThe findings suggest that neurometabolites levels in the PMC and FEF may be a promising candidate for clinical and pathological changes in ALS.}, } @article {pmid40395088, year = {2025}, author = {Zhang, S and Gu, J and Yang, Y and Li, J and Ni, L}, title = {Evolution Trend of Brain Science Research: An Integrated Bibliometric and Mapping Approach.}, journal = {Brain and behavior}, volume = {15}, number = {5}, pages = {e70451}, pmid = {40395088}, issn = {2162-3279}, support = {2020Z388//Jiangsu Postdoctoral Research Foundation/ ; //Top Talent Support Program for young and middle-aged people of the Wuxi Health Committee/ ; M202033//Wuxi Health Commission Scientific Research Project/ ; 24CC00903//Beijing Academy of Science and Technology Think Tank Research Project/ ; ZYYB05//Wuxi Administration of Traditional Chinese Medicine/ ; }, mesh = {*Bibliometrics ; Humans ; *Biomedical Research/trends ; *Neurosciences/trends ; *Brain/physiology ; United States ; China ; }, abstract = {BACKGROUND: Brain science research is considered the crown jewel of 21st-century scientific research; the United States, the United Kingdom, and Japan have elevated brain science research to a national strategic level. This study employs bibliometric analysis and knowledge graph visualization to map global trends, research hotspots, and collaborative networks in brain science, providing insights into the field's evolving landscape and future directions.

METHODS: We analyzed 13,590 articles (1990-2023) from the Web of Science Core Collection using CiteSpace and VOSviewer. Metrics included publication volume, co-authorship networks, citation patterns, keyword co-occurrence, and burst detection. Analytical tools such as VOSviewer, CiteSpace, and online bibliometric platforms were employed to facilitate this investigation.

RESULTS: The United States, China, and Germany dominated research output, with China's publications rising from sixth to second globally post-2016, driven by national initiatives like the China Brain Project. However, China exhibited limited international collaboration compared to the United States and European Union. Key journals included Human Brain Mapping and Journal of Neural Engineering, while emergent themes centered on "task analysis," "deep learning," and "brain-computer interfaces" (BCIs). Research clusters revealed three focal areas: (1) Brain Exploration (e.g., fMRI, diffusion tensor imaging), (2) Brain Protection (e.g., stroke rehabilitation, amyotrophic lateral sclerosis therapies), and (3) Brain Creation (e.g., neuromorphic computing, BCIs integrated with AR/VR). Despite China's high output, its influence lagged in highly cited scholars, reflecting a "quantity-over-quality" challenge.

CONCLUSION: Brain science research is in a golden period of development. This bibliometric analysis offers the first comprehensive review, encapsulating research trends and progress in brain science. It reveals current research frontiers and crucial directions, offering a strategic roadmap for researchers and policymakers to navigate countries when planning research layouts.}, } @article {pmid40394046, year = {2025}, author = {Ge, R and Chen, M and Wu, S and Huang, S and Zhou, P and Cao, M and Zhang, F and Zang, J and Zhu, Y and Li, J and Ni, G and Yang, Z and Li, Q and Pan, W and Zhang, L and Liu, M and Xuan, C and Yu, H and Zhou, J and Xie, S}, title = {DNA nanoflower Oligo-PROTAC for targeted degradation of FUS to treat neurodegenerative diseases.}, journal = {Nature communications}, volume = {16}, number = {1}, pages = {4683}, pmid = {40394046}, issn = {2041-1723}, support = {32270892//National Natural Science Foundation of China (National Science Foundation of China)/ ; 32200613//National Natural Science Foundation of China (National Science Foundation of China)/ ; }, mesh = {Humans ; *RNA-Binding Protein FUS/metabolism/genetics ; Animals ; Proteolysis ; *DNA/chemistry ; *Neurodegenerative Diseases/genetics/therapy/metabolism ; Blood-Brain Barrier/metabolism ; *Oligonucleotides ; Mice ; Brain/metabolism ; Receptors, Transferrin/metabolism ; Amyotrophic Lateral Sclerosis/genetics ; }, abstract = {Oligonucleotide-based medicine faces challenges in efficiently crossing the blood-brain barrier and rapidly reducing toxic proteins. To address these challenges, here we establish an integrated modality, brain-penetrant DNA nanoflowers incorporated with oligonucleotide-based proteolysis targeting chimeras. Using FUS as a proof-of-concept, mutations of which cause frontotemporal dementia and amyotrophic lateral sclerosis, we demonstrate that a FUS-engaging RNA oligonucleotide crosslinked to a ligand for Cereblon efficiently degrade FUS and its cytoplasmic disease-causing mutants through a ubiquitin-proteasomal pathway. The DNA nanoflower contains hundreds of oligonucleotide binding sites and transferrin receptor-engaging aptamers, allowing efficient loading of the oligonucleotide-based degrader and engaging transferrin receptors for brain delivery. A single dose intravenous injection of this modality reaches brain parenchyma within 2 h and degrades 80% FUS protein there, sustained for two weeks without noticeable toxicity. DNA nanoflower oligonucleotide-based degrader is a therapeutic strategy for neurodegenerative diseases that leverages the advantages of designer oligonucleotides and targeted protein degradation.}, } @article {pmid40392845, year = {2025}, author = {Beccari, MS and Arnold-Garcia, O and Baughn, MW and Artates, JW and McAlonis-Downes, M and Lim, J and Leyva-Cázares, DF and Rubio-Lara, HI and Ramirez-Rodriguez, A and Bernal-Buenrostro, CN and Murgia-Bay, B and Rangel, CK and Kim, DH and Melamed, Z and Lutz, CM and Lagier-Tourenne, C and Corbett, KD and López-Erauskin, J and Cleveland, DW}, title = {Stathmin-2 enhances motor axon regeneration after injury independent of its binding to tubulin.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {122}, number = {21}, pages = {e2502294122}, pmid = {40392845}, issn = {1091-6490}, support = {R35 GM144121/GM/NIGMS NIH HHS/United States ; T32 AG066596/AG/NIA NIH HHS/United States ; P30 NS047101/NS/NINDS NIH HHS/United States ; R35GM144121//HHS | NIH | National Institute of General Medical Sciences (NIGMS)/ ; T32GM008666//HHS | NIH | National Institute of General Medical Sciences (NIGMS)/ ; R01NS112503//HHS | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; P30NS047101//HHS | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; T32 GM008666/GM/NIGMS NIH HHS/United States ; R01 NS112503/NS/NINDS NIH HHS/United States ; N/A//Muscular Dystrophy Association (MDA)/ ; RF1 NS124203/NS/NINDS NIH HHS/United States ; T32AG066596//HHS | NIH | National Institute on Aging (NIA)/ ; R01 NS124203/NS/NINDS NIH HHS/United States ; N/A//NOMIS Stiftung (NOMIS Foundation)/ ; RF1NS124203//HHS | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; }, mesh = {Animals ; *Stathmin/metabolism/genetics ; *Axons/metabolism/physiology/pathology ; *Motor Neurons/metabolism/physiology/pathology ; Mice ; *Tubulin/metabolism ; *Nerve Regeneration/physiology ; Mice, Knockout ; Protein Binding ; Neuromuscular Junction/metabolism/pathology ; Humans ; Microtubules/metabolism ; }, abstract = {Stathmin-2 (also known as SCG10) is encoded by the STMN2 gene, whose mRNA is one of the most abundantly expressed in human motor neurons. In almost all instances of ALS and other TDP-43 proteinopathies, stathmin-2 encoding mRNAs are cryptically spliced and polyadenylated in motor neurons, a pathogenic consequence of nuclear loss of function of the RNA binding protein TDP-43. While stathmin-2 has been shown to enhance regeneration after axonal injury to axons of cultured motor neurons, here, we show that after crush injury within the adult murine nervous system of wild-type or stathmin-2-null mice, the presence of stathmin-2 reduces axonal and neuromuscular junction degeneration and stimulates reinnervation and functional recovery. Mechanistically, although stathmin-2 has been proposed to function through direct binding to α/β tubulin heterodimers and correspondingly to affect microtubule assembly and dynamics, stathmin-2's role in axon regeneration after axotomy is shown to be independent of its tubulin binding abilities.}, } @article {pmid40391540, year = {2025}, author = {Massey, C and Hobson, E and Griffiths, AW and Musson, L and McDermott, C}, title = {Exploring mechanisms of behavior change for healthcare professionals in cough and secretion management in ALS.}, journal = {Neurodegenerative disease management}, volume = {15}, number = {4}, pages = {149-160}, pmid = {40391540}, issn = {1758-2032}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/complications/therapy ; *Cough/therapy/etiology ; *Health Personnel/psychology ; Female ; Male ; Focus Groups ; Middle Aged ; Qualitative Research ; Adult ; }, abstract = {OBJECTIVES: To explore healthcare professionals' experiences managing cough and secretion problems in Amyotrophic Lateral Sclerosis (ALS).

METHODS: A qualitative study was completed with 23 individuals participating in four focus groups. Data was analyzed using reflexive thematic analysis and COM-B and theoretical domains framework (TDF) behavior change frameworks.

RESULTS: This study found that roles, responsibilities, and expectations needed to be clearly defined and that building relationships was important to support care delivery. Barriers identified included limited access to specialist care, equipment, and opportunities to gain knowledge and skills. A structured clinical assessment was highlighted to enable good-quality care. Data mapped most commonly to the environmental context/resources, knowledge, skills (TDF), and physical capability (COM-B) behavior change domains.

CONCLUSION: Cough and secretion management in ALS is complex due to the multifaceted nature of the disease. This study emphasizes the need for future development of clinical interventions to support care.}, } @article {pmid40390742, year = {2025}, author = {Franconieri, F and Fayolle, S and Raviol, P}, title = {Non-diabetic Ketoacidosis in a Patient With Amyotrophic Lateral Sclerosis: The Role of Stewart's Approach in Analyzing Acid-Base Disorders.}, journal = {Cureus}, volume = {17}, number = {4}, pages = {e82585}, pmid = {40390742}, issn = {2168-8184}, abstract = {Amyotrophic lateral sclerosis (ALS) is often complicated by severe malnutrition, increasing the risk of metabolic disturbances. Non-diabetic ketoacidosis (NDKA) is a rare but serious complication, typically related to prolonged fasting or catabolic states. A 62-year-old female patient with ALS and hypothyroidism presented with pneumonia and tetraplegia. Her body mass index (BMI) was 17 kg/m[2]. Laboratory findings showed a high anion gap (AG) metabolic acidosis (pH 7.23, bicarbonate 13 mmol/L, partial pressure of carbon dioxide (pCO2) 28 mmHg) without hyperlactatemia, but with significant ketonemia (5 mmol/L), severe hypophosphatemia, and signs of systemic inflammation. Upon admission, she received an intravenous infusion of 4.2% sodium bicarbonate. The simplified strong ion difference (SID) was preserved, excluding dilutional or hyperchloremic causes. Stewart's physicochemical approach, supported by a Gamblegram, revealed an acidosis due to unmeasured fixed acids, specifically ketone bodies. In light of this, bicarbonate therapy was discontinued, and nutritional correction with glucose hydration led to rapid clinical and biochemical improvement. This case illustrates the diagnostic and therapeutic value of Stewart's model in complex acid-base disturbances and underscores the need for early nutritional assessment in ALS patients. To our knowledge, this is the first reported case of NDKA in ALS, highlighting a rare but clinically relevant metabolic complication.}, } @article {pmid40390638, year = {2025}, author = {Oh, J and Chu, HS}, title = {Self-care mobile application for people with Amyotrophic Lateral Sclerosis: a development and usability test.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {}, number = {}, pages = {1-8}, doi = {10.1080/21678421.2025.2507169}, pmid = {40390638}, issn = {2167-9223}, abstract = {OBJECTIVE: Mobile technology can significantly enhance self-care for individuals with amyotrophic lateral sclerosis (ALS). This study aims to develop and evaluate the usability of a mobile application that provides relevant information and manages disease-related data for ALS patients and their families.

METHODS: A mobile application compatible with Android and iOS platforms was developed following the four phases of the System Development Life Cycle. The content was derived from a literature review, stakeholder focus group interviews, and in-depth interviews with ALS patients, family members, and healthcare professionals. The final application was validated by experts (n = 7), tested for usability by ALS patients and caregivers (n = 18), and evaluated using the System Usability Scale (SUS) to assess effectiveness and user satisfaction.

RESULTS: The application includes features such as tailored health data visualization, symptom tracking, text-to-speech functionality, and access to information customized based on the overall the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised score, thereby supporting patient-centered care and daily disease management. The mean SUS score was 75.00 ± 9.57 for expert panel members and 63.75 ± 10.26 for the target users, indicating an acceptable level of usability.

CONCLUSIONS: The mobile application was evaluated as practical, acceptable, and feasible for ALS patients and their caregivers, with positive feedback on its usability and potential to improve self-care management.}, } @article {pmid40389989, year = {2025}, author = {Noh, MY and Oh, SI and Kim, YE and Cha, SJ and Sung, W and Oh, KW and Park, Y and Mun, JY and Ki, CS and Nahm, M and Kim, SH}, title = {Mutations in NEK1 cause ciliary dysfunction as a novel pathogenic mechanism in amyotrophic lateral sclerosis.}, journal = {Molecular neurodegeneration}, volume = {20}, number = {1}, pages = {59}, pmid = {40389989}, issn = {1750-1326}, support = {RS-2023-00265515//Ministry of Science and ICT/ ; RS-2023-00265515//Ministry of Science and ICT/ ; 24-BR-02-04//Ministry of Science and ICT/ ; 25-BR-04-01//Ministry of Science and ICT, South Korea/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/pathology/metabolism ; *NIMA-Related Kinase 1/genetics/metabolism ; *Cilia/metabolism/pathology/genetics ; Mutation/genetics ; Female ; Male ; Middle Aged ; Motor Neurons/metabolism ; Fibroblasts/metabolism ; Adult ; }, abstract = {BACKGROUND: Neuronal primary cilia, vital for signaling and cell-cycle regulation, have been implicated in maintaining neuronal identity. While a link between primary ciliary defects and neurodegenerative diseases is emerging, the precise pathological mechanisms remain unclear.

METHODS: We studied the genetic contribution of NEK1 to ALS pathogenesis by analyzing the exome sequences of 920 Korean patients with ALS. To understand the disease contribution of NEK1 variants in ALS, we performed a series of functional studies using patient fibroblasts focusing on primary cilia and microtubule-related phenotypes. In addition, these findings were validated in iPSC-derived motor neurons (iPSC-MNs).

RESULTS: NIMA-related kinase 1 (NEK1), a gene encoding a serine/threonine kinase involved in cell cycle regulation, has been identified as a risk gene for amyotrophic lateral sclerosis (ALS). Here, we report that mutations in NEK1 cause primary ciliary abnormality, cell cycle re-entry, and disrupted tubulin acetylation in ALS. We analyzed the whole-exome sequences of 920 Korean patients with sporadic ALS and identified 16 NEK1 variants in 23 patients. We found that two novel variants, p.E853Rfs*9 and p.M1?, reduced NEK1 expression, resulting in loss-of-function (LOF) and one synonymous splicing variant (p.Q132=) exhibited an aberrant isoform lacking exon 5. All three NEK1 variants exhibited abnormal primary ciliary structure, impaired sonic hedgehog signaling, and altered cell-cycle progression. Furthermore, the ALS-linked variants induced intracellular calcium overload followed by Aurora kinase A (AurA)-histone deacetylase (HDAC)6 activation, resulting in ciliary disassembly. These defects were restored by treatment with the intracellular Ca[2+] chelator, BAPTA. We also found that NEK1 variants cause decreased α-tubulin acetylation, mitochondrial alteration, and impaired DNA damage response (DDR). Notably, drug treatment to inhibit HDAC6 restored the NEK1-dependent deficits in patient fibroblasts. And, we confirmed that data found in patient fibroblasts were reproduced in iPSC-MNs model.

CONCLUSIONS: Our results suggest that NEK1 contributes to ALS pathogenesis through the LOF mechanism, and HDAC6 inhibition provides an attractive therapeutic strategy for NEK1 variants associated ALS treatment.}, } @article {pmid40389567, year = {2025}, author = {Wu, WL and Gong, XX and Qin, ZH and Wang, Y}, title = {Molecular mechanisms of excitotoxicity and their relevance to the pathogenesis of neurodegenerative diseases-an update.}, journal = {Acta pharmacologica Sinica}, volume = {}, number = {}, pages = {}, pmid = {40389567}, issn = {1745-7254}, abstract = {Glutamate excitotoxicity is intricately linked to the pathogenesis of neurodegenerative diseases, exerting a profound influence on cognitive functions such as learning and memory in mammals. Glutamate, while crucial for these processes, can lead to neuronal damage and death when present in excessive amounts. Our previous review delved into the cascade of excitotoxic injury events and the underlying mechanisms of excitotoxicity. Building on that foundation, this update summarizes the latest research on the role of excitotoxicity in neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis, as well as new cutting-edge techniques applied in the study of excitotoxicity. We also explore the mechanisms of action of various excitotoxicity inhibitors and their clinical development status. This comprehensive analysis aims to enhance our understanding of the nexus between excitotoxicity and neurodegenerative diseases, offering valuable insights for therapeutic strategies in these conditions.}, } @article {pmid40389397, year = {2025}, author = {Schweingruber, C and Nijssen, J and Mechtersheimer, J and Reber, S and Lebœuf, M and O'Brien, NL and Mei, I and Hedges, E and Keuper, M and Benitez, JA and Radoi, V and Jastroch, M and Ruepp, MD and Hedlund, E}, title = {Single-cell RNA-sequencing reveals early mitochondrial dysfunction unique to motor neurons shared across FUS- and TARDBP-ALS.}, journal = {Nature communications}, volume = {16}, number = {1}, pages = {4633}, pmid = {40389397}, issn = {2041-1723}, support = {2020-01049//Vetenskapsrådet (Swedish Research Council)/ ; }, mesh = {*RNA-Binding Protein FUS/genetics/metabolism ; *Motor Neurons/metabolism/pathology ; *Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology ; *Mitochondria/metabolism/genetics/pathology ; Humans ; Single-Cell Analysis ; Induced Pluripotent Stem Cells/metabolism ; *DNA-Binding Proteins/genetics/metabolism ; Mutation ; Sequence Analysis, RNA ; Axons/metabolism ; C9orf72 Protein/genetics/metabolism ; Animals ; }, abstract = {Mutations in FUS and TARDBP cause amyotrophic lateral sclerosis (ALS), but the precise mechanisms of selective motor neuron degeneration remain unresolved. To address if pathomechanisms are shared across mutations and related to either gain- or loss-of-function, we performed single-cell RNA sequencing across isogenic induced pluripotent stem cell-derived neuron types, harbouring FUS P525L, FUS R495X, TARDBP M337V mutations or FUS knockout. Transcriptional changes were far more pronounced in motor neurons than interneurons. About 20% of uniquely dysregulated motor neuron transcripts were shared across FUS mutations, half from gain-of-function. Most indicated mitochondrial impairments, with attenuated pathways shared with mutant TARDBP M337V as well as C9orf72-ALS patient motor neurons. Mitochondrial motility was impaired in ALS motor axons, even with nuclear localized FUS mutants, demonstrating shared toxic gain-of-function mechanisms across FUS- and TARDBP-ALS, uncoupled from protein mislocalization. These early mitochondrial dysfunctions unique to motor neurons may affect survival and represent therapeutic targets in ALS.}, } @article {pmid40389223, year = {2025}, author = {Heimbuch, S and Tischler, L and Beyer, A and Jordan, Y and Pfeuffer, N and Krause, H and van den Berg, N}, title = {Telemedizin in der Pädiatrie - Akzeptanz und Zufriedenheit aus Elternperspektive.}, journal = {Gesundheitswesen (Bundesverband der Arzte des Offentlichen Gesundheitsdienstes (Germany))}, volume = {}, number = {}, pages = {}, doi = {10.1055/a-2543-3179}, pmid = {40389223}, issn = {1439-4421}, abstract = {The telemedical networking of children's clinics of varying sizes and specializations can support healthcare close to home, especially in rural regions with structural limitations. A Regional Tele-Paediatric Network was implemented in Mecklenburg-Western Pomerania and North Brandenburg (innovation fund project RTP-Net). This study examines the question of how participating parents accepted and evaluated this form of care.Parents of paediatric patients at a participating clinic were invited to take part in the study during the observation period 02.2021 to 03.2023 study. A mixed-methods approach was used that comprised a standardized questionnaire. The interviews were transcribed, categorized according to Kuckartz and subjected to descriptive evaluation. Between 12.2023 to 02.2024, telephone interviews were conducted with parents who had agreed to be recontacted.A total of 507 cases (403 patients) were included in the RTP-Net. Data from 138 questionnaires were analyzed. 74.5% of parents found that the use of telemedicine was helpful for the treatment of their child; 88.1% could imagine that telemedicine could supplement paediatric healthcare in the future. Parents interviewed over the telephone (n=11) rated telemedicine services positively. The main advantages mentioned were saving in time and distance, availability of specialist expertise and avoidance of long waiting times. There were concerns about the lack of physical contact between telemedicine doctor and patient.Parents show a high level of acceptance of telemedicine and trust in the provision of telemedical services. Telemedicine can help parents to avoid the burden of long journeys and waiting times and improve access to specialist medical expertise. In order to improve the acceptance and satisfaction of parents, it is important to inform them about the results if the telemedical advice was based on a doctor-to-doctor consultation.Die telemedizinische Vernetzung von Kinder-Kliniken unterschiedlicher Größen und Spezialisierungen kann insbesondere in ländlichen Regionen mit strukturellen Einschränkungen eine wohnortnahe Versorgung unterstützen. In Mecklenburg-Vorpommern und Nord-Brandenburg wurde ein Regionales Telepädiatrisches Netzwerk (Innovationsfondsprojekt RTP-Net) implementiert. In dieser Publikation wird der Frage nachgegangen, wie teilnehmende Eltern diese Versorgungsform akzeptierten und bewerteten.Der Mixed-Methods-Ansatz umfasste einen deskriptiv ausgewerteten standardisierten Fragebogen für Eltern, die ihr Kind im Beobachtungszeitraum 02.2021 bis 03.2023 in einer teilnehmenden Klinik vorstellten und an der Studie teilnahmen. Zwischen 12.2023 und 02.2024 wurden telefonische Interviews mit Eltern geführt, die einer Wiederkontaktierung zugestimmt hatten. Die Interviews wurden transkribiert und inhaltlich strukturierend nach Kuckartz kategorisiert und ausgewertet.Es wurden 507 Fälle (403 Patienten) in das RTP-Net eingeschlossen. Daten aus 138 Elternfragebögen wurden analysiert. 74,5% der befragten Eltern fanden, dass die Nutzung der Telemedizin hilfreich für die Behandlung ihres Kindes war. 88,1% von ihnen können sich vorstellen, dass Telemedizin die pädiatrische Versorgung zukünftig ergänzt. Es wurden elf Telefoninterviews geführt. Diese Eltern schätzten telemedizinische Angebote positiv ein. Als Vorteile galten v. a. die Weg- und Zeitersparnis, die Verfügbarkeit spezialfachärztlicher Expertise und die Vermeidung langer Wartezeiten. Bedenken bestanden in Bezug auf den fehlenden physischen Kontakt zwischen Telemedizinarzt und Patient. Um die Akzeptanz und Zufriedenheit der Eltern zu verbessern, ist es wichtig, diese über das Resultat zu informieren, wenn die telemedizinische Maßnahme als Arzt-zu-Arzt-Konsultation erfolgte.Auf Seiten der Eltern ist eine hohe Akzeptanz telemedizinischer Angebote und Vertrauen in die telemedizinische Leistungserbringung gegeben. Durch Telemedizin können Belastungen der Eltern durch lange Anfahrtswege und Wartezeiten vermieden werden und der Zugang zu spezialfachärztlicher Expertise verbessert werden.}, } @article {pmid40389171, year = {2025}, author = {Das, D and Das, A and Bhattacharya, K and Koch, KP and Deuri, DJ and Saikia, D and Chanu, NR and Deka, S}, title = {Xanthones as neuroprotective agents: A comprehensive review of their role in the prevention and treatment of neurodegenerative diseases.}, journal = {Ageing research reviews}, volume = {109}, number = {}, pages = {102772}, doi = {10.1016/j.arr.2025.102772}, pmid = {40389171}, issn = {1872-9649}, mesh = {*Xanthones/therapeutic use/pharmacology/chemistry ; Humans ; *Neuroprotective Agents/therapeutic use/pharmacology ; *Neurodegenerative Diseases/drug therapy/prevention & control ; Animals ; }, abstract = {Over the recent years, numerous research efforts have been focused toward xanthones, a class of heterocyclic compounds characterized by a three-ring core structure and a diverse range of biological activities. Despite extensive studies, no xanthone-based molecule has successfully progressed through clinical trials to reach pharmaceutical applications. Xanthones belong to the class of secondary metabolites that exist naturally, found in various plant species, and their structural diversity has been further expanded through synthetic modifications to enhance their pharmacological efficacy. This review provides a comprehensive description of the therapeutic potential of xanthone derivatives within the scope of neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, multiple sclerosis, and neuroinflammation. Existing literature has been rigorously examined to highlight the pharmacological relevance of xanthones in these disorders. Additionally, the pathophysiological aspects of each disease are discussed in detail to establish a mechanistic understanding of how xanthone derivatives may exert neuroprotective effects. Furthermore, the SAR of xanthones is explored to elucidate key molecular features responsible for their bioactivity, providing insights into rational drug design. By synthesizing and critically analyzing the existing research, this review is focused in highlighting the therapeutic relevance of xanthones in neurodegenerative diseases and their potential as lead candidates for further drug development.}, } @article {pmid40389143, year = {2025}, author = {Tan, X and Su, X and Wang, Y and Liang, W and Wang, D and Huo, D and Wang, H and Qi, Y and Zhang, W and Han, L and Zhang, D and Wang, M and Xu, J and Wang, S and Wang, J and Feng, H}, title = {COMM domain containing 4 inhibits hephaestin and ferroportin to enhance neuronal ferroptosis by disturbing the Cu-Fe balance in amyotrophic lateral sclerosis.}, journal = {Brain research}, volume = {1861}, number = {}, pages = {149707}, doi = {10.1016/j.brainres.2025.149707}, pmid = {40389143}, issn = {1872-6240}, mesh = {*Amyotrophic Lateral Sclerosis/metabolism ; *Ferroptosis/physiology ; Ferroportin ; Animals ; *Copper/metabolism ; *Cation Transport Proteins/metabolism ; Humans ; Iron/metabolism ; Neurons/metabolism ; *Membrane Proteins/metabolism ; Mice ; *Adaptor Proteins, Signal Transducing/metabolism ; Male ; Disease Models, Animal ; }, abstract = {Dysregulation of copper and iron homeostasis contributes to the progression of amyotrophic lateral sclerosis (ALS), but the role and mechanism of COMM domain containing 4 (COMMD4) in ALS remains unclear. In this research, we showed that the expression of COMMD4 was upregulated in ALS cells and animal models. The increased COMMD4 induced neuronal ferroptosis by disrupting the Cu-Fe balance. Mechanistic studies indicated that COMMD4 inhibited ferroportin (FPN)-mediated neuronal iron efflux by inhibiting intracellular copper and hephaestin (HEPH). Our findings demonstrated that COMMD4 depletion exerts neuroprotective effects on ALS by increasing intracellular copper and activating HEPH/FPN pathway, rather than affecting the interaction between HEPH and FPN. Targeting COMMD4 and its downstream signaling pathways may offer potential therapeutic avenues for ALS.}, } @article {pmid40389086, year = {2025}, author = {Pu, K and Yang, S and Sheng, R and Chen, J and Dai, Y and Wood, IC and Zhong, Z and Xu, S}, title = {Chuanxiong-Danggui herb pair alleviated cognitive deficits of APP/PS1 mice by promoting mitophagy.}, journal = {Journal of ethnopharmacology}, volume = {350}, number = {}, pages = {119988}, doi = {10.1016/j.jep.2025.119988}, pmid = {40389086}, issn = {1872-7573}, mesh = {Animals ; *Drugs, Chinese Herbal/pharmacology/therapeutic use ; Mice, Inbred C57BL ; *Mitophagy/drug effects ; *Cognitive Dysfunction/drug therapy ; Mice ; *Alzheimer Disease/drug therapy/pathology ; Amyloid beta-Protein Precursor/genetics ; Hippocampus/drug effects/pathology/metabolism ; Mice, Transgenic ; Male ; *Neuroprotective Agents/pharmacology ; Disease Models, Animal ; Presenilin-1/genetics ; Cell Line ; Dendritic Spines/drug effects ; Maze Learning/drug effects ; }, abstract = {Disruption of receptor-mediated mitophagy contributes to neuronal damage in Alzheimer's disease (AD). Chuanxiong-Danggui herb pair (CDHP) is classic herbal pair applied to treating neurodegenerative diseases including AD, Amyotrophic Lateral Sclerosis, Parkinson's disease. Though studies have demonstrated the neuroprotective effects of CDHP, the underlying mechanisms by which CDHP attenuates neuronal impairment of AD remains to be elucidated.

AIM OF THE STUDY: The objective of this work was to investigate the anti-AD mechanism of CDHP in APP/PS1 mice.

MATERIALS AND METHODS: Behavioral assessments were conducted on C57BL/6J and APP/PS1 mice following CDHP treatment, alongside an evaluation of neuronal morphology in the hippocampal region. In vitro, HT-22 cells were induced by Aβ25-35 before being treated with CDHP. The mechanisms of CDHP were investigated using transmission electron microscopy, Golgi staining, immunofluorescence, and Western blot analysis.

RESULTS: Results from the passive avoidance test and the Morris water maze (MWM) indicated that CDHP significantly mitigated cognitive deficits of APP/PS1 mice, accompanied by a reduction of pathological damage in the CA1 and CA3 regions of hippocampus. Further testing found that a significant reduction in dendritic spines density was rescued by CDHP. Synaptophysin (SYN) and postsynaptic density protein 95 (PSD-95) were elevated in the CDHP group, while β-amyloid (Aβ) plaques deposition was significantly reduced. Simultaneously, CDHP markedly inhibited neuronal apoptosis through a decrease of the levels of Cleaved Caspase-12 and enhanced expression of Bcl-2/Bax, both in vivo and in vitro. Additionally, CDHP improved mitochondrial morphology and function in the AD model by decreasing abnormal mitochondria and increasing the expression of COXIV. Transmission electron microscopy (TEM) revealed that clear mitophagy-autophagosomes were nearly absent in APP/PS1 mice, while the expression of p62 and LC3B were elevated following CDHP treatment. Furthermore, CDHP increased the expression of the FUNDC1 and PGAM5 in APP/PS1 mice and AD-like cell models.

CONCLUSION: These findings suggest that CDHP mitigated cognitive dysfunction in APP/PS1 mice by enhancing mitophagy to reduce neuronal injury.}, } @article {pmid40388677, year = {2025}, author = {de Vries, BS and de Boer, EMJ and Brugman, F and Van Damme, P and Veldink, JH and van Es, MA and van den Berg, LH}, title = {Primary Lateral Sclerosis: Implications for Diagnostic Criteria From a Natural History Study in the Netherlands.}, journal = {Neurology}, volume = {104}, number = {11}, pages = {e213461}, pmid = {40388677}, issn = {1526-632X}, mesh = {Humans ; Female ; Middle Aged ; Male ; *Motor Neuron Disease/diagnosis/epidemiology/physiopathology ; Aged ; Netherlands/epidemiology ; Disease Progression ; Amyotrophic Lateral Sclerosis/diagnosis ; Follow-Up Studies ; Adult ; Cohort Studies ; }, abstract = {BACKGROUND AND OBJECTIVES: Primary lateral sclerosis (PLS) is a rare disease characterized by upper motor neuron (UMN) degeneration. We aimed to elucidate the natural history in patients with UMN syndromes suggestive of PLS and validate the most recent diagnostic (consensus) criteria.

METHODS: A validation study of a long-term follow-up cohort was conducted, including adults with UMN syndromes and disease durations ≥6 months. Patients were assessed at baseline (T1), at 3 years (T2), and when possible after 13 years (T3). Diagnostic categorization followed the 2020 PLS consensus criteria. Main outcomes included diagnostic classification at follow-up and survival.

RESULTS: The study comprised 86 patients (34 women [40%], mean age 58.9 ± 10.1 years), of whom 43 met the PLS consensus criteria at baseline (6 probable, 37 definite). Eight patients had a disease duration <2 years, and 35 patients presented with UMN symptoms localized to 1 region (1 bulbar, 34 legs). Change of initial diagnosis occurred in 14% of patients with PLS, and 49% of patients presenting with UMN symptoms in 1 region progressed to PLS. Seven patients developed amyotrophic lateral sclerosis (ALS), and for 7 patients, diagnosis was revised to hereditary spastic paraplegia (HSP). Survival was shorter for patients with a disease duration <4 years. In the probable PLS group, 33% converted to ALS. Converters had a steeper Amyotrophic Lateral Sclerosis Functional Rating Scale slope (p = 0.023) and shorter symptom duration (p < 0.001) at inclusion. Of patients presenting with leg symptoms, diagnosis was revised between T2 and T3 in 29%. Introducing a 4-year minimal disease duration for PLS diagnosis and categorization based on regions involved resulted in 86% of PLS diagnoses remaining within the PLS category, 5% transitioning to ALS (slow variant), and 9% to HSP. Survival was longest for patients presenting with symptoms confined to arms and legs or legs only, followed by those with bulbar involvement at baseline, while patients with disease durations between 6 months and 4 years exhibited the shortest survival.

DISCUSSION: Our findings suggest that a diagnosis of PLS should be deferred until 4 years after symptom onset because shorter durations correlate with higher ALS conversion rates and shorter survival. Categorization by regional involvement may facilitate more effective monitoring of patients with UMN syndromes.}, } @article {pmid40388191, year = {2025}, author = {De Marchi, F and Lombardi, I and Bombaci, A and Diamanti, L and Olivero, M and Perciballi, E and Tornabene, D and Vulcano, E and Ferrari, D and Mazzini, L}, title = {Recent therapeutic advances in the treatment and management of amyotrophic lateral sclerosis: the era of regenerative medicine.}, journal = {Expert review of neurotherapeutics}, volume = {25}, number = {7}, pages = {773-789}, doi = {10.1080/14737175.2025.2508781}, pmid = {40388191}, issn = {1744-8360}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy ; *Regenerative Medicine/methods ; Genetic Therapy/methods ; Stem Cell Transplantation/methods ; Animals ; }, abstract = {INTRODUCTION: Despite decades of research, effective disease-modifying treatments for Amyotrophic Lateral Sclerosis (ALS) remain scarce. The emergence of regenerative medicine presents a new frontier for ALS treatment.

AREAS COVERED: This review is based on a comprehensive literature search using PubMed, Scopus and clinical trials databases on the recent therapeutic advancements in ALS, giving focus to regenerative medicine. The article includes coverage of stem cell-based therapies, including mesenchymal, neural and induced pluripotent stem cells; all of which may offer potential neuroprotective and immunomodulatory effects. Gene therapy, particularly antisense oligonucleotides targeting ALS-related mutations, has gained traction, with tofersen becoming the first FDA-approved genetic therapy for ALS. The article also covers emerging approaches such as extracellular vesicles, immune-modulating therapies, and bioengineering techniques, including CRISPR-based gene editing and cellular reprogramming, that hold promise for altering disease progression.

EXPERT OPINION: While regenerative medicine provides hope for ALS patients, significant challenges remain. Biomarkers will play a crucial role in guiding personalized treatment strategies, ensuring targeted interventions. Future research should prioritize optimizing combinatory approaches, integrating different therapy strategies to maximize patient outcomes. Although regenerative medicine is still in its early clinical stages, its integration into ALS treatment paradigms could redefine disease management and alter its natural course.}, } @article {pmid40386966, year = {2025}, author = {Honig, A and Dayan, R and Knaani, A and Levine, H and Gotkine, M}, title = {Military Service Roles and ALS Among Veterans: A Matched Case-Control Study.}, journal = {Annals of clinical and translational neurology}, volume = {12}, number = {8}, pages = {1702-1705}, pmid = {40386966}, issn = {2328-9503}, abstract = {While military service is an established risk factor for amyotrophic lateral sclerosis (ALS), it remains unclear whether this association is linked to combat. We conducted a matched case-control study comparing 191 ALS patients who were veterans of the Israeli Defense Forces (IDF) with known military service type and 1910 matched controls. The ALS group had higher rates of combat service (46.0% vs. 22.7%) and parachuting (10.5% vs. 1.1%) in comparison with controls (p < 0.001 for both). In a multivariate model, combat service was associated with ALS (odds ratio 2.49, confidence interval [1.49-4.16], p < 0.01). The higher prevalence of combat roles among ALS patients expands our understanding of military service factors that contribute to ALS risk.}, } @article {pmid40385899, year = {2025}, author = {Panganiban, ELC and Rosales, RL}, title = {Multiple System Atrophy (Cerebellar Type) With Overlapping Progressive Muscular Atrophy Features and Genetic Erb-B2 Receptor Tyrosine Kinase 4 (ERBB4) Amyotrophic Lateral Sclerosis Variant: A Case Report.}, journal = {Cureus}, volume = {17}, number = {4}, pages = {e82509}, pmid = {40385899}, issn = {2168-8184}, abstract = {Multiple system atrophy (MSA) is a progressive disease with Parkinsonism, dysautonomia, and cerebellar symptoms wherein patients can present with a broad range of confusing and overlapping findings attributable to various neuroanatomical substrates. Although possible, weakness is an unusual primary complaint, warranting further work-up for another neurodegenerative disease. The involvement of the more central structures, such as the locus coeruleus, pontine micturition center, and the cerebellum, can explain the wide range of symptoms. While Onuf's nucleus contributes to the urinary symptoms, anterior horn cells can implicate a motor neuron disease. Taking the varied neuroanatomical substrates into consideration, patients can present with a plethora of dysregulated motor symptoms. The authors share the course of a patient with clinically established MSA-cerebellar type and lower motor neuron disease findings at par with progressive muscular atrophy (PMA), but tested positive for an ERBB4 gene mutation, which is linked to an amyotrophic lateral sclerosis (ALS) variant. A 65-year-old Chinese female manifested with bilateral leg weakness and urinary incontinence. Over the next five years, she developed recurrent pre-syncopal attacks, asymmetric limb tremors, memory lapses, laughing fits, and a staccato-like voice. Medical management with anti-Parkinsonism drugs did not help her condition. Repeated annual non-contrast enhanced cranial magnetic resonance imaging (MRI) revealed gradual cerebellar atrophy, and an eventual prominent "hot-cross bun" sign. Because of episodes of orthostatic hypotension, with a systolic blood pressure as low as 50 mmHg, she gradually became bedridden with progressive arm weakness and sleep issues. These prompted her admission. Saccadic dysmetria and ataxic dysarthria aided in the diagnosis of MSA-cerebellar type, while motor neuron disease findings included tongue fasciculation, asymmetric leg atrophy, and polyminimyoclonus, suggestive of PMA. Neurophysiological studies confirmed this, while whole genome sequencing yielded an ERBB4 gene ALS variant of uncertain significance. She remained compliant with physical therapy during her admission. Although she was prescribed fludrocortisone for symptomatic relief and a two-week course of edaravone, she was discharged with minimal improvement and wheelchair-bound. However, the patient eventually expired two years afterward due to systemic complications. Although suspicion for a certain movement disorder can be initially made with physical examination, diagnostics can shed further light on the patient's pathology, exemplifying the uniqueness of this case report and how varying neurodegenerative movement disorders can coexist in a single patient.}, } @article {pmid40385805, year = {2025}, author = {Moutinho, A and Fontes, J and Ferreira, L and Lopes, J and Martins, F and Mega, S and Gil, M and Barros, F and Correia, AM}, title = {Sepsis Alerts in the Pre-hospital Setting: An Observational Retrospective Study of Emergency Medical Services' Response in Portugal (2020-2023).}, journal = {Cureus}, volume = {17}, number = {4}, pages = {e82528}, pmid = {40385805}, issn = {2168-8184}, abstract = {Background Sepsis is a life-threatening condition that demands prompt recognition and intervention to enhance patient outcomes. Early identification and timely treatment, particularly in the prehospital setting, are essential. Objective This study aims to characterize sepsis pre-alerts issued by the Portuguese Emergency Medical Services (EMS) early warning system between May 2020 and December 2023, focusing on adult patients. It provides an overview of the alert system and examines associated clinical data, therapeutic interventions, and hospital referrals. Methods A retrospective analysis was conducted on sepsis pre-alerts from the Portuguese EMS database. Data collected included patient demographics, comorbidities, National Early Warning Score (NEWS), interventions administered, and outcomes. Results A total of 537 sepsis alerts were identified, with a median patient age of 83 years. The majority of patients had significant cardiovascular and neurological comorbidities. The average NEWS was 11.74. Advanced Life Support (ALS) or Integrated Life Support (ILS) teams were required in 76.9% (N=413) of cases. Interventions included intravenous fluid administration in 49.3% (N=265), oxygen therapy in 46.2% (N=248), and vasopressor use in 3.9% (N=14). Conclusions Effective prehospital sepsis management is crucial for improving patient outcomes. Challenges such as delayed hospital transfers, often due to regional constraints, highlight the need for enhanced integration between EMS and hospital care. Future efforts should focus on optimizing early sepsis management, fostering collaboration between EMS and hospital teams, and exploring the feasibility of prehospital antibiotic administration.}, } @article {pmid40385376, year = {2025}, author = {Chamoun, S and Imrell, S and Upate, Z and Kläppe, U and Öijerstedt, L and Yazdani, S and Andersson Franko, M and Foucher, J and Azizi, L and Lovik, A and Samuelsson, K and Press, R and Fang, F and Svennberg, E and Juto, A and Ingre, C}, title = {Plasma troponin T reflects lower motor neuron involvement on electromyography in amyotrophic lateral sclerosis.}, journal = {Brain communications}, volume = {7}, number = {3}, pages = {fcaf177}, pmid = {40385376}, issn = {2632-1297}, abstract = {Cardiac troponin T (cTnT) is elevated in neuromuscular conditions without apparent cardiac disease, including Amyotrophic Lateral Sclerosis (ALS). The reason for this increase is unclear. Since cTnT is found in both cardiomyocytes and skeletal muscle cells, we aimed to investigate the latter as a possible cTnT source. We examined the correlation of cTnT in venous blood to lower motor neuron (LMN) involvement on Electromyography (EMG). A positive correlation between EMG findings and cTnT levels would indicate that cTnT is a biomarker for LMN involvement in ALS. This observational cohort study was conducted on a tertiary referral centre for neuromuscular diseases in Stockholm, Sweden. Consecutive patients with ALS were included. EMG was performed during diagnostic work-up, and high-sensitive cardiac troponin T (hs-cTnT), plasma creatine kinase (CK), and serum neurofilament light (NfL) were analysed within 6 months of the EMG. King's stage and score on the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) closest to hs-cTnT sampling were noted. In total, 50 ALS patients diagnosed between 1 January 2014 and 31 December 2018 were included and followed until death, invasive ventilation, or the 14 August 2024. Hs-cTnT correlated positively with the number of muscular regions involved (τ = 0.283, P = 0.009) and percentage of muscles involved on EMG (ρ = 0.367, P = 0.009). Hs-cTnT was associated with the percentage of muscles involved in EMG in the adjusted linear regression. Patients with higher hs-cTnT had more advanced King's stage, both when numerical hs-cTnT and subgrouping high (≥15 nanogram/L) versus normal hs-cTnT was used (τ = 0.253, P = 0.021 and U = 197.5, P = 0.022, respectively). Hs-cTnT was neither correlated to ALSFRS-R total score (ρ = -0.176, P = 0.220 and U = 249.5, P = 0.233, respectively) nor ALSFRS-R excluding respiratory domain score (ρ = -0.069, P = 0.632 and U = 280.5, P = 0.558, respectively). High versus normal hs-cTnT did not predict survival (univariate analysis, HR = 1.824, P = 0.060). Numerical hs-cTnT was associated with shorter survival (univariate analysis, HR = 1.635, P = 0.017) but not after adjusting for age at diagnosis (HR = 1.413, P = 0.105). This study illustrates that ALS patients with higher hs-cTnT have more spread disease as evidenced by the positive correlation between hs-cTnT and both EMG and King's stage. This is not true for established biomarkers of muscle damage (CK) and neuroaxonal damage (NfL). These findings need to be confirmed in larger studies but suggest that hs-cTnT is a biomarker of LMN involvement in patients with ALS and could be used in clinical trials.}, } @article {pmid40384653, year = {2025}, author = {Bai, C and Leng, Y and Xiao, H and Li, L and Cui, W and Li, T and Dong, Y and Zheng, J and Cai, X}, title = {A deep-learning model for predicting post-stroke cognitive impairment based on brain network damage.}, journal = {Quantitative imaging in medicine and surgery}, volume = {15}, number = {5}, pages = {3964-3981}, pmid = {40384653}, issn = {2223-4292}, abstract = {BACKGROUND: Post-stroke cognitive impairment (PSCI) is a common and severe complication following acute lacunar stroke (ALS). Due to the limitations of current assessment tools and imaging methods, the early diagnosis of PSCI within 3 months of ALS remaining challenging. This study aimed to develop an effective, reliable, and accurate deep-learning method to predict PSCI within 3 months of ALS.

METHODS: In total, 100 ALS patients were enrolled in the study, of whom 39 were diagnosed with PSCI and 61 were non-PSCI. First, we quantified three-dimensional (3D) gray-matter damage and white-matter tract disconnection, providing both regional damage (RD) and structural disconnection (SDC) higher-dimensional insights into brain network disruption. Second, we developed a novel deep-learning model based on ResNet18, integrating 3D RD, SDC, and diffusion-weighted imaging (DWI) to provide a comprehensive analysis of brain network integrity and predict PSCI. Finally, we compared the performance of our method with other methods, and visualized brain network damage associated with PSCI.

RESULTS: Our model showed strong predictive performance and had a mean accuracy (ACC) of 0.820±0.024, an area under the curve (AUC) of 0.795±0.068, a sensitivity (SEN) of 0.746±0.121, a specificity (SPE) of 0.869±0.044, and a F1-score (F1) of 0.760±0.050 in the five-fold cross-validation, outperforming existing models. In the PSCI patients, brain network damage significantly affected the salience, default mode, and somatic motor networks.

CONCLUSIONS: This study not only established a model that can accurately predict PSCI, it also identified potential targets for symptom-based treatments, offering new insights into PSCI.}, } @article {pmid40384575, year = {2025}, author = {Vogt, C and Weber, M and Schneider, U and Neuwirth, C}, title = {Quinine Sulfate for Muscle Cramps in Amyotrophic Lateral Sclerosis: A Randomized, Double-Blind Crossover Trial.}, journal = {Muscle & nerve}, volume = {72}, number = {2}, pages = {267-273}, doi = {10.1002/mus.28440}, pmid = {40384575}, issn = {1097-4598}, support = {//Swiss ALS foundation/ ; //Hänseler AG/ ; }, mesh = {Humans ; *Quinine/therapeutic use ; Double-Blind Method ; *Muscle Cramp/drug therapy/etiology ; Male ; *Amyotrophic Lateral Sclerosis/complications/drug therapy ; Female ; Cross-Over Studies ; Middle Aged ; Aged ; Adult ; Treatment Outcome ; Muscle Relaxants, Central/therapeutic use ; }, abstract = {INTRODUCTION/AIMS: Many patients with amyotrophic lateral sclerosis (ALS) experience muscle cramps during the course of the disease. This study aimed to evaluate the efficacy of orally administered quinine sulfate for muscle cramps in ALS patients.

METHODS: We conducted a randomized, double-blind, placebo-controlled crossover trial in ALS patients experiencing daily muscle cramps. After a two-week run-in period, patients were assigned to receive 250 mg quinine sulfate once daily, followed by a placebo or vice versa. Each treatment period lasted 2 weeks and was followed by a 4-week washout period. Patients used a daily diary to rate muscle cramp intensity on the numeric rating scale (NRS) and record muscle cramp frequency. The primary outcome measure was change in cramp intensity; coprimary outcome measures were number of muscle cramps during daytime and nighttime.

RESULTS: Data from four women and three men were included in the analysis, all of whom reported a notable reduction in cramp intensity and frequency, leading them to continue the medication. Quinine sulfate was well-tolerated, with two patients reporting mild tinnitus. Cramp intensity was significantly reduced by 48% (p = 0.042). Further, the number of daytime muscle cramps declined significantly (p = 0.024).

DISCUSSION: Our findings suggest the potential efficacy of quinine sulfate in reducing muscle cramp intensity and frequency in ALS patients. However, the small sample size (n = 7) limits generalizability. Larger, multicenter studies are needed to confirm these results and fully assess its safety, serious adverse events, and therapeutic potential.}, } @article {pmid40384352, year = {2025}, author = {Yuan, Y and Fu, Y and Wang, X and Hu, F and Zhao, Q and He, C and Tang, L and Li, Y and Bu, Y and Song, X and Liu, Q and Liu, Z and Xu, R and Cao, W and Zhang, Y and Yi, X and Wang, J and Chen, BT}, title = {Shape Alterations of Subcortical Nuclei Correlate With Amyotrophic Lateral Sclerosis Progression.}, journal = {Brain and behavior}, volume = {15}, number = {5}, pages = {e70495}, pmid = {40384352}, issn = {2162-3279}, support = {81300981//National Natural Science Foundation of China/ ; 81671120//National Natural Science Foundation of China/ ; 82171431//National Natural Science Foundation of China/ ; U22A20377//National Natural Science Foundation of China/ ; 2021ZD0201803//Science and Technology Innovation 2030/ ; 2020LNJJ13;2022LNJJ09//Project Program of National Clinical Research Center for Geriatric Disorders (Xiangya hospital)/ ; 2022JJ30979//Natural Science Foundation of Hunan Province/ ; 2021YFA0805202//National Key Research and Development Program of China/ ; 2022M713536//China Post-Doctoral Science Foundation/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/pathology/diagnostic imaging/physiopathology ; Male ; Female ; Disease Progression ; Middle Aged ; Magnetic Resonance Imaging/methods ; Aged ; Brain Stem/pathology/diagnostic imaging ; Neuroimaging/methods ; Basal Ganglia/pathology/diagnostic imaging ; Adult ; Thalamus/pathology/diagnostic imaging ; Brain/pathology/diagnostic imaging ; Prospective Studies ; }, abstract = {BACKGROUND: Neuroimaging has been increasingly used to assess brain structural alterations in patients with amyotrophic lateral sclerosis (ALS). We aimed to investigate alterations in brain sub-cortical structures and to identify potential neuroimaging biomarkers for disease progression for patients with ALS.

METHODS: A total of 61 patients with ALS were prospectively enrolled and were divided into three subgroups according to disease progression, i.e., fast, intermediate, and slow progression. Sixty-one matched healthy controls (HCs) were also recruited. All participants acquired a brain structural magnetic resonance imaging scan for subcortical volumetric and shape analyses. Neuropsychological testing and functional assessment were performed.

RESULTS: Patients with fast progression showed significant shape alterations in basal ganglia and brainstem as compared to the HCs group. In ALS patients with fast progression, shape contractions with atrophic changes were noted in bilateral nucleus accumbens, left caudate, left thalamus, and brainstem; while shape expansion with hypertrophy was noted in the left caudate, left thalamus, and left pallidum (all p < 0.05). There were significant positive correlations of the shape changes of the left thalamus with the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALS-FRS-R) total and limb scores and with disease duration (all p < 0.05). There were positive correlations of left pallidum with anxiety or with disease duration, and of left nucleus accumbens with ALS-FRS-R total or bulbar score, and of brainstem with mini-mental state examination score (all p < 0.05).

CONCLUSION: Extensive shape alterations of subcortical nuclei were noted in patients with fast progression of ALS, implicating subcortical shape being a potential neuroimaging biomarker for ALS progression.}, } @article {pmid40384011, year = {2025}, author = {Changqing, L and Leying, Y and Caiyun, M and Hebao, W and Laiguo, H and Xiaojiang, Z}, title = {Causal Relationships Between the Gut Microbiota, Inflammatory Cytokines, and Amyotrophic Lateral Sclerosis: A Mendelian Randomization Analysis.}, journal = {Brain and behavior}, volume = {15}, number = {5}, pages = {e70571}, pmid = {40384011}, issn = {2162-3279}, support = {//Philosophy and Social Sciences Foundation of the Anhui Higher Education Institutions of China/ ; //Provincial Quality Engineering Project of Higher Education Institutions of Anhui Province/ ; //Natural Science Foundation of the Higher Education Institutions of Anhui Province/ ; 202310367042//National College Students Innovation and Entrepreneurship Training Program/ ; //innovation and entrepreneurship training program for college students/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/genetics/microbiology ; Humans ; Mendelian Randomization Analysis ; *Gastrointestinal Microbiome/genetics/physiology ; *Cytokines/metabolism/genetics ; Genome-Wide Association Study ; Inflammation ; }, abstract = {BACKGROUND: The relationship between gut microbiota (GM) and amyotrophic lateral sclerosis (ALS) is well-documented. However, the causal nature of this association and the potential mediating role of inflammatory cytokines (ICs) have yet to be elucidated.

METHODS: We performed Mendelian randomization (MR) analyses utilizing data derived from genome-wide association studies (GWAS) of GM, ICs, and ALS. Initially, we conducted bidirectional two-sample MR analysis to determine the causal relationships between GM, ICs, and ALS. Subsequently, a two-step MR mediation analysis was performed to investigate the role of ICs as mediators. The primary statistical approach was the inverse variance weighted (IVW) method.

RESULTS: Through MR analysis, we identified one positive causal relationship and three negative causal relationships between GM and ALS. There was one positive association and one negative association between ICs and ALS. In addition, ICs do not appear to mediate the pathway from GM to ALS.

CONCLUSION: This study established a causal relationship between GM, ICs, and ALS, suggesting that ICs do not function as mediators in the pathway from GM to ALS. These findings provide new perspectives on potential ALS prevention and treatment strategies.}, } @article {pmid40383997, year = {2025}, author = {Foucher, J and Wellander, T and Lovik, A and Öijerstedt, L and Juto, A and Fang, F and Ingre, C}, title = {Venous Bicarbonate as a Prognostic Biomarker and Proposed Proxy for Vital Capacity to Be Used as an Eligibility Criterion in Amyotrophic Lateral Sclerosis Clinical Trials.}, journal = {Brain and behavior}, volume = {15}, number = {5}, pages = {e70570}, pmid = {40383997}, issn = {2162-3279}, support = {//Ulla-Carin Lindquists stiftelse för ALS-forskning/ ; //Neuro Sweden/ ; /CC/CDC HHS/United States ; //R01TS000324-02-01/ ; //Demensförbundet/ ; //Svenska Frimurarorden/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/blood/physiopathology/diagnosis/mortality ; Male ; Female ; Middle Aged ; Biomarkers/blood ; Prognosis ; *Bicarbonates/blood ; Aged ; Vital Capacity/physiology ; Sweden ; Registries ; Clinical Trials as Topic ; }, abstract = {BACKGROUND: Clinical trials for people living with ALS (pALS) all list vital capacity (VC) as an important eligibility criterion. However, VC measures are challenging to perform among pALS, especially bulbar pALS. Additionally, since the disease rapidly changes, the VC can change in a short duration of time, making it unreliable.

OBJECTIVE: We aimed to investigate the association of venous bicarbonate with VC as an alternative criterion for trial eligibility. We also wanted to examine whether venous bicarbonate could be used as a prognostic biomarker for survival in ALS.

METHODS: We included pALS from the Swedish ALS/MND Registry between January 1, 2019 and July 31, 2022. pALS had to have serum bicarbonate values and ALSFRS-R available close to diagnosis. Spearman correlations, Kaplan-Meier curves, and Cox proportional hazard regressions were used to assess the associations of venous bicarbonate with VC, other clinical characteristics, and survival.

RESULTS: Among the 117 pALS included in the study, we observed a negative correlation between venous bicarbonate and VC among spinal and bulbar pALS (ρ = -0.346, p = 0.002 and ρ = -0.367, p = 0.024, respectively). Venous bicarbonate negatively correlated with ALSFRS-R (ρ = -0.377, p < 0.001), specifically among bulbar pALS (ρ = -0.595, p < 0.001), but positively correlated with KING's stage (ρ = 0.248, p = 0.007). High level of venous bicarbonate appeared to be associated with shorter survival.

CONCLUSIONS: Venous bicarbonate appears to be a prognostic biomarker for survival among pALS. This cheap and easily accessible measure could potentially be an alternative for VC as an eligibility criterion in ALS trials.}, } @article {pmid40383620, year = {2025}, author = {Ibáñez-Cervantes, JL and Vargas-de León, C and Veléz-Reséndiz, JM and Fernández-Sánchez, V and Saavedra-Bravo, R and Bandala, C and Olvera-Gómez, I and Mancilla-Ramírez, J and Ibáñez-Cervantes, G}, title = {Association of ALS genes in strains of the genus Candida with cervical cytological alterations.}, journal = {Indian journal of medical microbiology}, volume = {54}, number = {}, pages = {100795}, doi = {10.1016/j.ijmmb.2025.100795}, pmid = {40383620}, issn = {1998-3646}, mesh = {Humans ; Female ; Adult ; Mexico ; *Candidiasis, Vulvovaginal/microbiology/pathology ; Middle Aged ; *Candida/genetics/isolation & purification/classification/enzymology ; *Cervix Uteri/pathology/microbiology ; Young Adult ; *Fungal Proteins/genetics ; Polymerase Chain Reaction ; Candida albicans/genetics/isolation & purification ; Aged ; }, abstract = {PURPOSE: Fungi are an important cause of human infection and include infections caused by Candida species. Vaginal candidiasis is a mycosis caused by several species of the genus Candida. In Mexico, it is considered the only mycosis that must be reported to health authorities. The participation and/or contribution of Candida ALS genes to the presence of cervical cytological alterations is currently unknown. The purpose of this study was to elucidate the frequency of Candida ALS genes and their association with clinical characteristics.

METHODS: The number of randomly selected samples was 697, of which 53 were Candida positive. Samples were selected from women attending gynaecological outpatient clinics for cervical cancer screening at Hospital Juarez de Mexico. These strains were identified, and genomic DNA was obtained from each isolate. Molecular assays were performed by endpoint PCR amplification of ALS genes.

RESULTS: The predominant Candida species identified in the study were Candida tropicalis and Candida albicans. ALS1 12 (22.6 %) and ALS3 19 (35.8 %) genes were found. ALS2, ALS4, ALS5, ALS6, ALS7, and ALS9 genes were not detected. ALS1 was the gene that was associated with patients using corticosteroids.

CONCLUSIONS: Vulvovaginitis remains one of the most prevalent conditions in patients in their 20s and 30s, and it is a real public health problem. Further studies are needed to determine the direct involvement of the identified ALS genes in the pathogen's ability to adhere and how it causes transient change in vaginal cytology.}, } @article {pmid40382904, year = {2025}, author = {Montemerlo, AE and Azcarate, SM and Camiña, JM and Messina, G}, title = {Development of a chemometrics-assisted electrochemical sensor applied to gallic acid quantification in food samples.}, journal = {Food chemistry}, volume = {487}, number = {}, pages = {144737}, doi = {10.1016/j.foodchem.2025.144737}, pmid = {40382904}, issn = {1873-7072}, mesh = {*Gallic Acid/analysis ; *Electrochemical Techniques/methods/instrumentation ; *Chemometrics/methods/instrumentation ; Fruit/chemistry ; *Food Analysis/instrumentation/methods ; Tea/chemistry ; Limit of Detection ; }, abstract = {Gallic acid (GA) is an abundant natural phenolic compound found in foods such as tea, fruits, and beverages. Quantifying GA remains a key research area in analytical chemistry. Traditional methods, such as liquid chromatography, are time-consuming, highlighting the need for faster and more efficient techniques to quantify GA concentration. This study proposes an approach based on the MCR-ALS algorithm to model second-order voltammetric data obtained by varying the scan rate. Data preprocessing and subsequent mathematical modeling enabled the quantification of GA with a detection limit of 5.9 mg L[-1], below the stipulated concentrations for the analyte in various food matrices. Quantification was achieved even in the presence of unmodeled interferences, leveraging the second-order capabilities of multivariate calibration methods. This approach allows for accurate results to be obtained in a direct, fast, and reliable manner, representing a breakthrough in food industry quality control and opening new perspectives for food quality assessment.}, } @article {pmid40381433, year = {2025}, author = {Begh, MZA and Zehravi, M and Bhuiyan, MAK and Molla, MR and Raman, K and Emran, TB and Ullah, MH and Ahmad, I and Osman, H and Khandaker, MU}, title = {Recent advances in stem cell approaches to neurodegeneration: A comprehensive review with mechanistic insight.}, journal = {Pathology, research and practice}, volume = {271}, number = {}, pages = {156013}, doi = {10.1016/j.prp.2025.156013}, pmid = {40381433}, issn = {1618-0631}, mesh = {Humans ; *Neurodegenerative Diseases/therapy ; *Stem Cell Transplantation/methods ; Animals ; }, abstract = {The progressive nature of neurodegenerative diseases (NDs), such as Parkinson's disease, Alzheimer's disease, Huntington's disease, and amyotrophic lateral sclerosis, presents substantial problems because current treatments are still obscure. Stem cell-based treatments are emerging as a viable solution to address the significant gaps in treating these severe diseases. This study provides a comprehensive analysis of the latest advancements in stem cell research, focusing on the treatment of NDs. Various types of stem cells, such as adult, induced pluripotent, and embryonic stem cells, and their potential applications in immunomodulation, neurotrophic factor release, and neuronal development are also discussed. Recent clinical studies reveal outcomes, challenges, and solutions, with advancements in disease-specific neural cell production, gene editing, and improved stem cell transplantation transport strategies. The review discussed future perspectives on developing more effective stem cell-based interventions. Biomaterials are being used for cell distribution and personalized medicine techniques to improve treatment outcomes, while exploring stem cell treatments for NDs and identifying areas for further research.}, } @article {pmid40381165, year = {2025}, author = {Esperante, I and Banzan, C and Munuera, JZ and Lima, A and Hunt, H and De Kloet, ER and Deniselle, MCG and De Nicola, AF and Meyer, M}, title = {The Selective Glucocorticoid Receptor Modulator Cort125329 Decreases Neuroinflammation and Gliosis and Enhances Myelination in the Wobbler Model of Amyotrophic Lateral Sclerosis.}, journal = {Molecular neurobiology}, volume = {}, number = {}, pages = {}, pmid = {40381165}, issn = {1559-1182}, support = {PIP 2017PIP 2019 #11220170100002CO//Consejo Nacional de Investigaciones Científicas y Técnicas/ ; PIP 2017PIP 2019 #11220170100002CO//Consejo Nacional de Investigaciones Científicas y Técnicas/ ; PIP 2017PIP 2019 #11220170100002CO//Consejo Nacional de Investigaciones Científicas y Técnicas/ ; PIP 2017PIP 2019 #11220170100002CO//Consejo Nacional de Investigaciones Científicas y Técnicas/ ; PIP 2017PIP 2019 #11220170100002CO//Consejo Nacional de Investigaciones Científicas y Técnicas/ ; PIP 2017PIP 2019 #11220170100002CO//Consejo Nacional de Investigaciones Científicas y Técnicas/ ; PICT 2021 00389//Ministry of Science, Technology and Innovative Production of Argentina/ ; PICT 2021 00389//Ministry of Science, Technology and Innovative Production of Argentina/ ; PICT 2021 00389//Ministry of Science, Technology and Innovative Production of Argentina/ ; PICT 2021 00389//Ministry of Science, Technology and Innovative Production of Argentina/ ; PICT 2021 00389//Ministry of Science, Technology and Innovative Production of Argentina/ ; AFDN grant//CORCEPT Therapeutics/ ; AFDN grant//CORCEPT Therapeutics/ ; AFDN grant//CORCEPT Therapeutics/ ; AFDN grant//CORCEPT Therapeutics/ ; AFDN grant//CORCEPT Therapeutics/ ; AFDN grant//CORCEPT Therapeutics/ ; 20020170100224BA)//Universidad de Buenos Aires/ ; 20020170100224BA)//Universidad de Buenos Aires/ ; }, abstract = {The Wobbler mouse is a genetic model of familial amyotrophic lateral sclerosis. Wobblers show spinal cord neurodegeneration associated with gliosis, neuroinflammation, and demyelination. Like human neurodegenerative diseases, Wobblers show high levels of corticosterone in the blood and the nervous system. The role of glucocorticoids in neuropathology is suggested by the observation that pathological signs attenuate with treatment with glucocorticoid receptor (GR) antagonists/modulators. In the present study, we demonstrated in 5-month-old clinically afflicted Wobbler mice that the selective GR modulator CORT125329 decreased motoneuron degeneration, astro- and microgliosis, and levels of pro-inflammatory factors (HMGB1, toll-like receptor 4, tumor necrosis factor α, and its receptor). In addition, CORT125329 increased the acetylcholine-producing enzyme choline acetyltransferase, the neurotrophin brain-derived neurotrophic factor, and their cellular colocalization. Furthermore, the increased oligodendrocyte number and a healthier myelin ultrastructure are consistent with the enhanced axonal myelination after CORT125329 treatment. Finally, the high expression of immunoreactive protein and mRNA levels of aquaporin4 in Wobblers was decreased by CORT125329 treatment, implying this water channel is a glucocorticoid target involved in neuropathology. The beneficial effects of CORT125329 correlated with enhanced motor behavioral performance and trophic changes of the forelimbs. In conclusion, our results support further preclinical and clinical studies on GR modulators in sporadic amyotrophic lateral sclerosis.}, } @article {pmid40379483, year = {2025}, author = {Lester, DG and Thompson, AG and Talbot, K and Turner, MR}, title = {Progression and life expectancy in primary lateral sclerosis.}, journal = {Journal of neurology, neurosurgery, and psychiatry}, volume = {}, number = {}, pages = {}, doi = {10.1136/jnnp-2025-336037}, pmid = {40379483}, issn = {1468-330X}, abstract = {OBJECTIVES: To characterise the clinical characteristics and longitudinal outcomes in primary lateral sclerosis (PLS), including median survival from symptom onset and age at death.

METHODS: The authors retrospectively reviewed electronic health records of patients diagnosed with PLS referred to a specialised motor neuron disorders clinic from 2002 to 2024, analysed longitudinal Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) assessments using joint models and used Kaplan-Meier methods and life tables to calculate median survival and age at death compared with population-based values.

RESULTS: Of 52 patients, 34 (65%) were male, 41 (79%) first noted symptoms in the lower limbs and 10 (19%) in corticobulbar function. Median age of symptom onset was 53 years. The mean annual rate of functional decline was -1.92 ALSFRS-R points (95% CI -3.03 to -0.78), with equal highest rates of decline in fine and gross motor subscores. Five patients (10%) received gastrostomy and three (6%) non-invasive ventilation. Median survival from symptom onset was 23.1 years (22.7 to not reached), and median age at death was 79.5 years (77.8 to not reached) compared with a population-based reference mean of 81.9 years (81.1 to 82.8).

DISCUSSION: PLS may be commensurate with near-normal life expectancy. Significant disability arises from limb motor dysfunction, with a minority of patients requiring nutritional or respiratory support. This has important implications for counselling and trial design.}, } @article {pmid40379219, year = {2025}, author = {Konopka, A and Jamali, MS and Fowler, M and Mehta, P and Parakh, S and Takalloo, Z and Farzana, F and Mumtaz, N and Hunter, J and Shadfar, S and Rogers, ML and Atkin, JD}, title = {Pathological forms of TDP-43 in amyotrophic lateral sclerosis (ALS) promote aberrant telomere elongation.}, journal = {Biochimica et biophysica acta. Molecular basis of disease}, volume = {1871}, number = {7}, pages = {167906}, doi = {10.1016/j.bbadis.2025.167906}, pmid = {40379219}, issn = {1879-260X}, mesh = {*Amyotrophic Lateral Sclerosis/genetics/pathology/metabolism ; Animals ; *DNA-Binding Proteins/genetics/metabolism ; Mice ; Telomeric Repeat Binding Protein 2/metabolism/genetics ; *Telomere/metabolism/genetics/pathology ; Humans ; Disease Models, Animal ; Motor Neurons/metabolism/pathology ; Male ; Neurons/metabolism/pathology ; Mice, Transgenic ; *Telomere Homeostasis ; Mutation ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder affecting motor neurons. TAR DNA-binding protein 43 (TDP-43) mis-localisation from the nucleus to the cytoplasm is the major pathological characteristic of ALS. Telomeres are repetitive DNA sequences found in complex with proteins at chromosomal ends. The shelterin protein complex protects telomeres from DNA damage by producing characteristic t-loop structures, and telomere repeat binding factor 2 (TRF2) has an essential role in this process. Telomere dysregulation is reported in ALS, but conflicting findings have been obtained. Here we examined if telomere dysregulation is present in cortical neurons in a mouse model with pathological mis-localisation of TDP-43 to the cytoplasm - TDP-43 rNLS - compared to controls, and in cortical primary neurons expressing TDP-43 ALS associated mutations (A315T, A90V). We demonstrate that telomeres are significantly longer and of more variable in length in the TDP-43 rNLS model compared to controls. This was proceeded by downregulation of TRF2 in early disease stages with subsequent upregulation of TRF2 at advanced disease in TDP-43 rNLS mice. Longer telomeres were also present in primary cortical neurons expressing mutant TDP-43. A trend towards TRF2 upregulation was also present in human ALS spinal cord lysates. We detected dysregulation of catalytic subunit of telomerase, TERT, and a trend towards upregulation of telomere interacting protein, Rif 1 in these mice and human ALS spinal cord lysates. The longer telomeres were independent of the alternative lengthening of telomeres (ALT) mechanism of maintaining telomere length. Similarly, no DNA damage at telomere sites was detected. Our findings imply that telomere protection is compromised in ALS, leading to longer telomeres in neurons in ALS associated with TDP-43 pathology.}, } @article {pmid40378897, year = {2025}, author = {Fontanelli, L and Nisini, N and Pirola, S and Recchia, FA}, title = {Neuromuscular and cardiac organoids and assembloids: Advanced platforms for drug testing.}, journal = {Pharmacology & therapeutics}, volume = {272}, number = {}, pages = {108876}, doi = {10.1016/j.pharmthera.2025.108876}, pmid = {40378897}, issn = {1879-016X}, mesh = {*Organoids/drug effects ; Humans ; Animals ; Induced Pluripotent Stem Cells/cytology ; Drug Evaluation, Preclinical/methods ; *Neuromuscular Junction/drug effects ; }, abstract = {The inherent technical difficulties, ethical/regulatory issues and costs of experimental studies in animal models is prompting investigators to replace as much as possible living organisms with in vitro physiological models named organoids and assembloids. Generated from induced pluripotent stem cells, these three-dimensional structures approximate the complexity of tissues and their interactions, enabling personalized disease modelling and drug testing. The integration of multiple components in assembloids further enhances their predictive value for multi-system interactions and toxicities. This review describes how neuromuscular organoids, incorporating functional neuromuscular junctions and contractile muscle tissue, have been used to replicate, in vitro, complex neuromuscular morpho-functional structures, offering very valuable platforms to study molecular mechanisms and drug effects in models of incurable diseases such as spinal muscular atrophy and amyotrophic lateral sclerosis. In the cardiological field, cardiac organoids and assembloids are proving reliable models for testing drug effects at molecular, morphological, electrophysiological and mechanical level. Recently, the integration of neuronal components into cardiac organoids has provided a potential approach to investigate autonomic function, a fundamental aspect of many neurological, neuromuscular and cardiac diseases. Challenges and limitations still remain, including the non-uniform differentiation protocols across studies, the incomplete maturation of cell phenotypes, and the lack of integrated pharmacokinetic modelling. We discussed some future developments aimed at overcoming such hurdles. Despite their current limitations, organoids and assembloids clearly hold great promises and will help advancing many fields of biomedicine.}, } @article {pmid40378485, year = {2025}, author = {Keating, ME and Byrne, HJ}, title = {Seeding multivariate algorithms for spectral analysis, a data augmentation approach to enhance analytical performance.}, journal = {Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy}, volume = {340}, number = {}, pages = {126369}, doi = {10.1016/j.saa.2025.126369}, pmid = {40378485}, issn = {1873-3557}, mesh = {Humans ; *Algorithms ; Principal Component Analysis ; Multivariate Analysis ; *Spectrum Analysis, Raman/methods ; Least-Squares Analysis ; A549 Cells ; Discriminant Analysis ; Cisplatin/pharmacology ; }, abstract = {Seeding spectral datasets by augmenting the data matrix with either the full spectrum or selected spectral features in order to bias multivariate analysis towards the solution of interest is explored. It is demonstrated that such seeding can have a profound effect on the endpoint of the analysis. Using Raman spectroscopic data of human lung adenocarcinoma cells (A549) in vitro, systematic perturbations to the spectra are introduced to simulate dose dependent exposure to a drug (cisplatin), and/or cellular response, representing reduced viability. Taking Principal Components Analysis (PCA) as the first example, seeding with the known spectral profiles of the drug exposure is demonstrated to greatly increase the ability of the algorithm to differentiate two distinct data subsets, representing control and exposed. The improved differentiation is quantified by further Linear Discriminant Analysis of the PCA data. Other examples of where seeding may be applied include, simulated datasets consisting of simultaneous changes in the spectral markers of exposure dose and cellular response, which are used for Multivariate Curve Resolution - Alternating Least Squares analysis (MCR-ALS). In the example presented, adding pure components to the dataset improves the ability of the algorithm to both model the systematic variation of concentration dependent data and extract the component spectra more accurately than the unseeded dataset. The seeded approach thus provides improved performance for differential analysis of datasets, as well as spectral unmixing analyses, to monitor, for example, the kinetic evolution of a reaction mixture, or metabolic pathway.}, } @article {pmid40378471, year = {2025}, author = {Birylo, M and Błaszczak-Bąk, W and Suchocki, C}, title = {Application of GLDAS models and ALS point clouds in assessing the impact of modified evapotranspiration on the water budget.}, journal = {Water research}, volume = {283}, number = {}, pages = {123746}, doi = {10.1016/j.watres.2025.123746}, pmid = {40378471}, issn = {1879-2448}, mesh = {*Water ; Climate Change ; Rain ; Models, Theoretical ; Hydrology ; Seasons ; Environmental Monitoring ; }, abstract = {Monitoring and assessing the water budget is crucial, especially in the context of climate change and increasing occurrences of extreme weather events. The water budget is influenced by precipitation, evapotranspiration, and surface runoff, which are shaped by meteorological conditions. Additionally, terrain topography and land cover structure play a significant role, although they are often overlooked in water budget calculations. This study presents the integration of data from the Global Land Data Assimilation System (GLDAS) and airborne laser scanning (ALS) point clouds, enabling a comprehensive analysis of hydrological processes. The results highlight that modified evapotranspiration significantly affects water availability, particularly in regions with diverse topography, where terrain features influence local hydrological conditions. The findings confirm that precipitation remains the dominant factor in the water budget, but terrain-driven variations in evapotranspiration contribute to seasonal and spatial differences. The study demonstrates that incorporating ALS-derived vegetation and terrain data into hydrological modeling improves the accuracy of water budget assessments, which is crucial for sustainable water resource management.}, } @article {pmid40375549, year = {2025}, author = {Kuiper, MM and Kruithof, WJ and Broekman-Peters, N and Schröder-van den Nieuwendijk, DL and Visser-Meily, JMA and Beelen, A}, title = {Nutritional care practices in ALS: perspectives of healthcare professionals and people with ALS.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {26}, number = {5-6}, pages = {452-466}, doi = {10.1080/21678421.2025.2501681}, pmid = {40375549}, issn = {2167-9223}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diet therapy/epidemiology/complications ; Male ; Female ; *Health Personnel/psychology ; Middle Aged ; Surveys and Questionnaires ; Nutritional Status ; Aged ; Netherlands ; *Malnutrition/etiology/diagnosis ; *Nutrition Therapy/methods ; Adult ; }, abstract = {Objective: To map nutritional care provided to people with ALS, PMA and PLS (pwALS) and identify barriers encountered by healthcare professionals and pwALS. Methods: Two online questionnaires, addressing current nutritional management of ALS in the Netherlands, were sent to healthcare professionals of the 36 certified ALS care teams and pwALS drawn from a population-based registry. Topics were: 1) contact between pwALS and their ALS care team, 2) monitoring nutritional status, 3) nutritional advice provided or received, and 4) satisfaction with current nutritional care and barriers encountered. Results: In total, 100 healthcare professionals and 372 pwALS completed the questionnaires. Dietitian responses (n = 36/100) showed that 28% utilized malnutrition screening tools and 17% measured body composition. Dietitians used different predictive equations to estimate energy and protein requirements. Patient responses showed that 50% had contact with a dietitian, 7% indicated body composition had been measured and 25% reported never being weighed or weighing themselves. Healthcare professionals and pwALS highlighted the need for comprehensive, up-to-date information on nutrition and ALS, national consensus on nutritional advice and monitoring methods, patient information material, training for healthcare professionals and personalized nutritional advice for pwALS. Conclusions: Practice variation was observed in the assessment and monitoring of nutritional status and the provision of nutritional advice. Suboptimal monitoring of nutritional status and estimation of nutritional requirements may result in delayed detection of malnutrition and inaccurate dietary recommendations. Further research and national consensus on monitoring methods and nutritional advice is required.}, } @article {pmid40375307, year = {2025}, author = {Trautwig, AN and Fox, EJ and Dammer, EB and Shantaraman, A and Ping, L and Duong, DM and Watson, CM and Wu, F and Asress, S and Guo, Q and Levey, AI and Lah, JJ and Verde, F and Doretti, A and Ratti, A and Ticozzi, N and Ly, CV and Miller, TM and Garret, MA and Berry, JD and Thomas, EV and Fournier, CN and McEachin, ZT and Seyfried, NT and Glass, JD}, title = {Network analysis of the cerebrospinal fluid proteome reveals shared and unique differences between sporadic and familial forms of amyotrophic lateral sclerosis.}, journal = {Molecular neurodegeneration}, volume = {20}, number = {1}, pages = {58}, pmid = {40375307}, issn = {1750-1326}, support = {R01 NS138499./NH/NIH HHS/United States ; No grant ID//Muscular Dystrophy Association/ ; RF-2021-12374238//Italian Ministry of Health/ ; 1RO1NS137434/NH/NIH HHS/United States ; NS097816/NH/NIH HHS/United States ; R01 NS138499/NS/NINDS NIH HHS/United States ; No Grant ID//Italian Ministry of Education and Research/ ; AG070937/NH/NIH HHS/United States ; P01NS084974/NS/NINDS NIH HHS/United States ; No grant ID//Association of Frototemporal Dementia/ ; P30AG066511//National Institute of Aging/ ; No Grant ID//Biogen, Inc/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/cerebrospinal fluid/genetics ; Male ; Female ; Middle Aged ; *Proteome ; C9orf72 Protein/genetics ; Proteomics/methods ; Biomarkers/cerebrospinal fluid ; Aged ; Superoxide Dismutase-1/genetics ; Adult ; Cohort Studies ; }, abstract = {BACKGROUND: Amyotrophic Lateral Sclerosis (ALS), a neurodegenerative disease involving loss of motor neurons, typically results in death within 3-5 years of disease onset. Although roughly 10% of cases can be linked to a specific inherited mutation (e.g., C9orf72 hexanucleotide repeat expansion or SOD1 mutation), the cause(s) of most cases are unknown. Consequently, there is a critical need for biomarkers that reflect disease onset and progression across ALS subgroups.

METHODS: We employed tandem mass tag mass spectrometry (TMT-MS) based proteomics on cerebrospinal fluid (CSF) to identify and quantify 2105 proteins from sporadic, C9orf72, and SOD1 ALS patients, asymptomatic C9orf72 expansion carriers, and controls (N = 101). To verify trends in our Emory University cohort we used data-independent acquisition (DIA-MS) on an expanded, four center cohort. This expanded cohort of 259 individuals included 50 sporadic ALS (sALS), 43 C9orf72 ALS, 22 SOD1 ALS, 72 asymptomatic gene carriers (59 C9orf72 and 13 SOD1) and 72 age-matched controls. We identified 2330 proteins and used differential protein abundance and network analyses to determine how protein profiles vary across disease subtypes in ALS CSF.

RESULTS: Differential abundance and co-expression network analysis identified proteomic differences between ALS and control, as well as differentially abundant proteins between sporadic, C9orf72 and SOD1 ALS. A panel of proteins differentiated forms of ALS that are indistinguishable in a clinical setting. An additional panel differentiated asymptomatic from symptomatic C9orf72 and SOD1 mutation carriers, marking a pre-symptomatic proteomic signature of genetic forms of ALS. Leveraging this large, multicenter cohort, we validated our ALS CSF network and identified ALS-specific proteins and network modules.

CONCLUSIONS: This study represents a comprehensive analysis of the CSF proteome across sporadic and genetic causes of ALS that resolves differences among these ALS subgroups and also identifies proteins that distinguish symptomatic from asymptomatic gene carriers. These new data point to varying pathogenic pathways that result in an otherwise clinically indistinguishable disease.}, } @article {pmid40374790, year = {2025}, author = {Verma, KK and Gaur, PK and Gupta, SL and Lata, K and Kaushik, R and Sharma, V}, title = {Metabolomics: a new frontier in neurodegenerative disease biomarker discovery.}, journal = {Metabolomics : Official journal of the Metabolomic Society}, volume = {21}, number = {3}, pages = {67}, pmid = {40374790}, issn = {1573-3890}, mesh = {Humans ; *Neurodegenerative Diseases/metabolism/diagnosis ; *Biomarkers/metabolism/analysis ; *Metabolomics/methods ; Animals ; }, abstract = {BACKGROUND: Neurodegenerative disorders are a group of debilitating diseases affecting the central nervous system, and are characterized by the progressive loss of neurons, leading to declines in cognitive function, movement, and overall quality of life. While the exact causes remain elusive, it's believed that a combination of genetic, environmental, and lifestyle factors contribute to their development. Metabolites, the end products of cellular processes, reflect the physiological state of an organism. By analysing these molecules, researchers can gain a deeper understanding of the underlying metabolic changes associated with neurodegenerative disorders.

AIM OF REVIEW: This review aims to explore the possibilities between metabolites and their association with neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), Parkinson's disease (PD), Multiple sclerosis (MS) and Huntington's disease (HD).

Metabolomic studies could potentially illuminate altered biochemical pathways, facilitating earlier detection and treatment of these conditions. Metabolomic investigations have revealed the role of oxidative stress, alterations in glucose and fat metabolism, mitochondrial dysfunction, apoptosis, glutamate excitotoxicity and alterations in myelin composition in neurodegenerative disorders. The common metabolic biomarkers identified includes glutamate, taurine, uric acid, branched chain amino acids, acylcarnitine, creatinine, choline, with some more amino acids and lipids. Metabolomics offers valuable insights into disease mechanisms and potential therapeutic targets by identifying biochemical and metabolic alterations, but still there are several aspects to be explored for accurate mapping of metabolites with specific pathway involved in the disease.}, } @article {pmid40374755, year = {2025}, author = {Krishnan, D and Talbot, DL and Ashhurst, JF and Park, SB and Vucic, S and Timmins, HC and Kiernan, MC}, title = {Longitudinal assessment of cortical motor function in amyotrophic lateral sclerosis.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {16978}, pmid = {40374755}, issn = {2045-2322}, support = {1156093//National Health and Medical Research Council/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology/diagnosis ; *Motor Cortex/physiopathology ; Male ; Female ; Middle Aged ; Transcranial Magnetic Stimulation ; Longitudinal Studies ; Evoked Potentials, Motor/physiology ; Aged ; Adult ; Disease Progression ; Prospective Studies ; }, abstract = {Background Short interval intracortical inhibition (SICI) remains the most sensitive parameter to assess motor cortical function in amyotrophic lateral sclerosis (ALS). While an initial value of SICI has been utilised to support a diagnosis of ALS, less is known about progression of change. Methods Motor cortex function was prospectively assessed in ALS patients, through serial threshold tracking transcranial magnetic stimulation (TMS) assessment over more than 12 months. Motor cortical potentials were recorded from the abductor pollicis brevis (APB). Demographic information and clinical variables were analysed. Results A cohort of 52 ALS patients (69.2% limb-onset disease; 47.2% right-side) were assigned to undergo longitudinal assessment of cortical motor function. Mean ALSFRS-R score at baseline was 39.5 ± 1.0 denoting relatively milder clinical deficits at study commencement. Cortical motor dysfunction was evident at baseline, with reduction in averaged SICI (p = 0.004) when compared to healthy controls. In terms of disease trajectory, ALS patients experienced a significant decline in averaged SICI overtime. When compared to initial assessment, averaged SICI was significantly reduced after 12 months (p = 0.004). There was no significant main effect of site of onset on averaged SICI (p = 0.78). The progressive change in averaged SICI was more robust in the dominant hemisphere, with the proportion of ALS patients who demonstrated a clinically abnormal averaged SICI value (< 5.5%) increasing by 50%, compared to 15.4% for the non-dominant hemisphere. Conclusion ALS patients demonstrate progressive cortical motor abnormalities, evident through longitudinal assessment. While SICI represents a diagnostic biomarker, the rate of decline in the present series is consistent with disease progression, suggesting a potential role to monitor the efficacy of therapeutic intervention.}, } @article {pmid40374720, year = {2025}, author = {Usategui-Martín, R and Esteban-López, V and Chantre-Fortes, E and Sánchez-Martín, M and Riancho, JA and López, DE and González-Sarmiento, R}, title = {The p.R321C mutation in the p62 protein is associated with abnormalities in the central nervous system.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {16929}, pmid = {40374720}, issn = {2045-2322}, mesh = {Animals ; *Sequestosome-1 Protein/genetics/metabolism ; Mice ; Humans ; Autophagy/genetics ; *Mutation ; *Central Nervous System/metabolism/pathology/abnormalities ; Disease Models, Animal ; NF-kappa B/metabolism ; Male ; Seizures/genetics/pathology ; }, abstract = {SQSTM1/p62 has an essential role in autophagy, a catabolic pathway that is vital for maintaining cell homeostasis. p62 alterations have been observed in multiple pathological conditions, including neurodegenerative diseases and bone metabolism alterations. The p.R321C p62 protein mutation has been described in patients with amyotrophic lateral sclerosis, frontotemporal lobar degeneration, and Paget's disease of bone. In vitro studies associated the p62-321C variant with a blockade of autophagy and with the activation of the NF-kB pathway. We aimed to provide a deeper understating of the pathophysiological consequences of the p.R321C p62 mutation using a humanized mouse model. Micro-computed tomography, immunohistochemistry, and western blot analysis studied the functional consequences of the p. R321C p62 mutation. Statistical analyses were performed using SPSS software. The results showed that the p62-321C mice developed seizures after tactile-vestibular stimulation, probably associated with a blockage of the autophagy and NF-kB activation. Changes in expression of cFos and p62 were found in the amygdala, hypothalamic nuclei, and hippocampi nuclei. In addition, numerous degenerating motor neurons were observed in the spinal cord of the p62-321C mice. We report that the blockage of the autophagy, caused by p.R321C p62 mutation, is associated with abnormalities in the central nervous system, mainly seizures after tactile-vestibular stimulation and degeneration of the motor neurons of the spinal cord but not with bone abnormalities in a humanized mouse model.}, } @article {pmid40373763, year = {2025}, author = {Wu, J and Song, H and Arkin, M and Zhang, S and Huang, X and Fan, D and Xu, Y}, title = {Characteristics of Neuromuscular Ultrasound in Patients with Amyotrophic Lateral Sclerosis.}, journal = {Neuro-degenerative diseases}, volume = {}, number = {}, pages = {1-11}, doi = {10.1159/000546425}, pmid = {40373763}, issn = {1660-2862}, abstract = {INTRODUCTION: Neuromuscular ultrasound has been increasingly used in the detection and diagnosis of amyotrophic lateral sclerosis (ALS), commonly characterized by peripheral nerve atrophy, degeneration, and muscle fasciculations. The aim of this study was to assess the ultrasound characteristics of ALS patients.

METHODS: A total of 67 consecutive patients with sporadic ALS and 19 with ALS mimics (63.16% peripheral neuropathy) were recruited. Ultrasound and electrophysiological examinations were performed; the peripheral nerve cross-sectional area (CSA) and fasciculation grades were compared between the groups, and correlations between ultrasound and electrophysiological data in ALS patients were determined.

RESULTS: ALS patients had smaller proximal median and ulnar nerve CSAs than those of ALS mimics, who exhibited asymmetric changes. Fasciculation differences in the trapezius, triceps brachii, extensor digitorum communis, thenar, and first dorsal interosseous muscles were observed. In ALS patients, the CSA and fasciculation relative scores were correlated with electrophysiological indicators.

CONCLUSION: Ultrasound is a valuable tool for monitoring peripheral nerve CSA and muscle fasciculations, both of which correlate with electrophysiological indices, in ALS patients.}, } @article {pmid40373575, year = {2025}, author = {de Carvalho, M}, title = {The F-wave fingerprint of amyotrophic lateral sclerosis.}, journal = {Neurophysiologie clinique = Clinical neurophysiology}, volume = {55}, number = {4}, pages = {103080}, doi = {10.1016/j.neucli.2025.103080}, pmid = {40373575}, issn = {1769-7131}, } @article {pmid40373480, year = {2025}, author = {Jih, KY and Fang, SY and Tsai, YS and Sytwu, HP and Liao, YC and Lee, YC}, title = {TARDBP variants in Taiwanese ALS patients: Genetic spectrum, clinical features, and founder effects.}, journal = {Journal of the neurological sciences}, volume = {474}, number = {}, pages = {123531}, doi = {10.1016/j.jns.2025.123531}, pmid = {40373480}, issn = {1878-5883}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/epidemiology ; Male ; Female ; Middle Aged ; Taiwan/epidemiology ; *DNA-Binding Proteins/genetics ; *Founder Effect ; Aged ; Adult ; Polymorphism, Single Nucleotide/genetics ; Haplotypes ; Cohort Studies ; *Genetic Predisposition to Disease ; Age of Onset ; }, abstract = {BACKGROUND: TARDBP is one of the most commonly implicated genes in amyotrophic lateral sclerosis (ALS). It encodes TAR DNA-binding protein 43 (TDP-43), a protein critical to ALS pathology, whose pathogenic variants disrupt its nuclear-cytoplasmic translocation, leading to aggregation. This study aimed to investigate the role of TARDBP variants in a Taiwanese ALS cohort.

METHODS: We analyzed the coding regions of TARDBP using Sanger sequencing in 650 unrelated ALS patients recruited between 2000 and 2024. The cohort included 388 men and 262 women, with an average age of onset of 56 ± 13 years. Approximately 20 % presented with bulbar-onset ALS. Haplotype analysis was conducted using single nucleotide polymorphism and short tandem repeat markers flanking TARDBP.

RESULTS: Pathogenic TARDBP variants were identified in 17 probands and 11 of their relatives, with an average age of onset of 49.1 ± 10.3 years, 32 % of whom had bulbar-onset disease. Six probands carried the p.M337V variant, five had p.S375G, two had p.N378D, and one each carried p.G348C, p.G348V, p.G376D, or p.I383V. Haplotype analysis suggested a common founder for the p.S375G variant and most families with p.M337V. Asymptomatic carriers were also identified, suggesting incomplete penetrance.

CONCLUSIONS: Our study revealed that pathogenic TARDBP variants are a significant genetic contributor to ALS in Taiwan, associated with earlier disease onset but reduced penetrance. The recurrent M337V and p.S375G variants likely reflect a founder effect.}, } @article {pmid40370030, year = {2025}, author = {Fusaro, L and Bangari, DS and Pasterkamp, RJ and Fernández-Ruiz, J and Youssef, SA and Sharma, AK}, title = {Neurodegenerative Diseases: Pathogenesis and Preclinical Models for Translational Drug Discovery.}, journal = {Toxicologic pathology}, volume = {53}, number = {4}, pages = {364-371}, doi = {10.1177/01926233251339105}, pmid = {40370030}, issn = {1533-1601}, mesh = {*Neurodegenerative Diseases/drug therapy/pathology ; Animals ; Humans ; *Disease Models, Animal ; *Drug Discovery/methods ; Translational Research, Biomedical ; Drug Evaluation, Preclinical ; }, abstract = {The fourth session of the 2024 European Society of Toxicologic Pathology (ESTP) Congress brought together lectures focused on the use of in vitro and in vivo models to investigate neurodegenerative diseases. Four presentations highlighted various aspects of neurodegenerative diseases including dementia, immune-mediated conditions, and neuromuscular disorders. The session began with an overview of animal models of dementia underscoring their critical role in understanding disease pathogenesis and supporting the development of effective therapeutic drugs. Subsequent presentations investigated immunological self-tolerance in autoimmune neurodegenerative diseases, such as multiple sclerosis and Guillain-Barré syndrome, and the application of in vitro models to study neuromuscular diseases such as amyotrophic lateral sclerosis. The final presentation examined cannabinoid-based therapeutic options for treating neurodegenerative diseases, highlighting their potential in neuroprotection and neurorepair. This session provided valuable insights into the latest research and advancements in neurodegenerative disease modeling and therapy, offering promising directions for improved modeling and therapeutic strategies.}, } @article {pmid40369342, year = {2025}, author = {Uechi, H and Sridharan, S and Nijssen, J and Bilstein, J and Iglesias-Artola, JM and Kishigami, S and Casablancas-Antras, V and Poser, I and Martinez, EJ and Boczek, E and Wagner, M and Tomschke, N and de Jesus Domingues, AM and Pal, A and Doeleman, T and Kour, S and Anderson, EN and Stein, F and Lee, HO and Zhang, X and Fritsch, AW and Jahnel, M and Fürsch, J and Murthy, AC and Alberti, S and Bickle, M and Fawzi, NL and Nadler, A and David, DC and Pandey, UB and Hermann, A and Stengel, F and Davis, BG and Baldwin, AJ and Savitski, MM and Hyman, AA and Wheeler, RJ}, title = {Small-molecule dissolution of stress granules by redox modulation benefits ALS models.}, journal = {Nature chemical biology}, volume = {}, number = {}, pages = {}, pmid = {40369342}, issn = {1552-4469}, support = {103261/Z/13/Z//Wellcome Trust (Wellcome)/ ; R01 GM147677/GM/NIGMS NIH HHS/United States ; 390729961//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; R01GM147677//U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)/ ; STE 2517/1-1//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; EP/V011359/1//RCUK | Engineering and Physical Sciences Research Council (EPSRC)/ ; STE 2517/5-1//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; }, abstract = {Neurodegenerative diseases, such as amyotrophic lateral sclerosis, are often associated with mutations in stress granule proteins. Aberrant stress granule condensate formation is associated with disease, making it a potential target for pharmacological intervention. Here, we identified lipoamide, a small molecule that specifically prevents cytoplasmic condensation of stress granule proteins. Thermal proteome profiling showed that lipoamide stabilizes intrinsically disordered domain-containing proteins, including SRSF1 and SFPQ, which are stress granule proteins necessary for lipoamide activity. SFPQ has redox-state-specific condensate dissolving behavior, which is modulated by the redox-active lipoamide dithiolane ring. In animals, lipoamide ameliorates aging-associated aggregation of a stress granule reporter protein, improves neuronal morphology and recovers motor defects caused by amyotrophic lateral sclerosis-associated FUS and TDP-43 mutants. Thus, lipoamide is a well-tolerated small-molecule modulator of stress granule condensation, and dissection of its molecular mechanism identified a cellular pathway for redox regulation of stress granule formation.}, } @article {pmid40366870, year = {2025}, author = {Arguedas, A and Schneck, D and Cui, E and Xenopoulos-Oddsson, A and Arcila-Londono, X and Lunetta, C and Wymer, J and Olney, N and Gwathmey, K and Ajroud-Driss, S and Hayat, G and Heiman-Patterson, T and Cerri, F and Fournier, C and Glass, J and Sherman, A and Walk, D and Fiecas, M}, title = {Risk prediction for ALS using semi-competing risk models with applications to the ALS Natural History Consortium dataset.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {26}, number = {5-6}, pages = {550-557}, doi = {10.1080/21678421.2025.2500359}, pmid = {40366870}, issn = {2167-9223}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/epidemiology/therapy ; Female ; Male ; Disease Progression ; Middle Aged ; Aged ; Risk Assessment/methods ; Gastrostomy ; Risk Factors ; }, abstract = {Background and objectives: Important landmarks in progression of amyotrophic lateral sclerosis (ALS) can occur prior to death. Predictive models for the risk of these events can assist in clinical trial design and personal planning. We propose a predictive model, using a semi-competing risks modeling approach, for five important disease progression landmarks in ALS. Methods: Data on 1508 participants from the ALS Natural History Consortium (ALS NHC) were used, including baseline characteristics and the ALS Functional Rating Scale-Revised (ALSFRS-R) score collected at clinic visits. A semi-competing risks modeling approach was used to study the time to disease progression landmarks, accounting for the possibility of death. Specifically, time to gastrostomy, use of noninvasive ventilation (NIV), continuous use of NIV, loss of speech, and loss of ambulation were chosen and modeled individually. To measure the predictive capabilities of the model, the integrated Brier score was computed for each model using cross-validation for the NHC data. Data from Emory University were used for external validation of the models. Results: We present model results using gastrostomy as the intermediate outcome. Similar trends in disease progression groups were found across all model pathways. Diagnostic delay, age, and site of onset were the most important covariates. Predictive metrics in both internal and external validation are presented across all models and for different pathways. Conclusion: Semi-competing risks modeling is a flexible approach to studying disease progression. The models have good predictive capabilities across different outcomes and pathways. These are replicated in the external validation dataset.}, } @article {pmid40366590, year = {2025}, author = {Wu, H and He, Q and Wang, Q}, title = {Histochemical Assays for Analyzing Abscission Layer Development and Function in Rice.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {2916}, number = {}, pages = {99-107}, pmid = {40366590}, issn = {1940-6029}, mesh = {*Oryza/growth & development/physiology/metabolism/genetics ; *Histocytochemistry/methods ; Gene Expression Regulation, Plant ; }, abstract = {This chapter outlines detailed methods and protocols for studying the structure and mechanisms of abscission layers (ALs) in rice. Utilizing rice spikelets as a primary example, these protocols provide comprehensive techniques for analyzing AL development, including tissue preparation, microscopy, and histochemical assays. The AL is a specialized tissue where cell separation takes place, and it is crucial for processes such as organ shedding and fruit drop. By examining the AL, researchers can uncover the physiological and genetic factors governing plant organ separation. These insights are pertinent for advancing agricultural practices and crop improvement, as understanding the dynamics of the AL can lead to the development of rice varieties with enhanced traits related to abscission and grain retention. These improvements can result in better yield stability and reduced post-harvest losses, which are essential for meeting the food demands of a growing global population. By focusing on the genetic and physiological mechanisms governing the AL, researchers can develop innovative strategies to optimize rice production and contribute to food security.}, } @article {pmid40365999, year = {2025}, author = {Gao, Z and Qiu, R and Dave, DR and Chandravanshi, P and Soares, GP and Smith, CS and Ortega, JA and Palmer, LC and Álvarez, Z and Stupp, SI}, title = {Supramolecular Copolymerization of Glycopeptide Amphiphiles and Amyloid Peptides Improves Neuron Survival.}, journal = {Journal of the American Chemical Society}, volume = {147}, number = {21}, pages = {17710-17724}, doi = {10.1021/jacs.5c00105}, pmid = {40365999}, issn = {1520-5126}, mesh = {Humans ; *Neurons/cytology/drug effects ; Cell Survival/drug effects ; *Amyloid beta-Peptides/chemistry ; Polymerization ; *Glycopeptides/chemistry/pharmacology ; *Surface-Active Agents/chemistry/pharmacology ; }, abstract = {Neurodegenerative diseases such as Alzheimer's disease and amyotrophic lateral sclerosis are characterized by progressive neuronal loss and the accumulation of misfolded proteins including amyloid proteins. Current therapeutic options include the use of antibodies for these proteins, but novel chemical strategies need to be developed. The disaccharide trehalose has been widely reported to prevent misfolding and aggregation of proteins, and we therefore investigated the conjugation of this moiety to biocompatible peptide amphiphiles (TPAs) known to undergo supramolecular polymerization. Using X-ray scattering, circular dichroism, and infrared spectroscopy, we found that trehalose conjugation destabilized the internal β-sheet structures within the TPA supramolecular polymers as evidenced by a lower thermal transition. Thioflavin T fluorescence showed that these metastable TPA nanofibers suppressed A42 aggregation. Interestingly, we found that the suppression involved supramolecular copolymerization of TPA polymers with Aβ42, which effectively trapped the peptides within the filamentous structures. In vitro assays with human induced pluripotent stem cell-derived neurons demonstrated that these TPAs significantly improved neuron survival compared to other conditions. Our study highlights the potential of properly tuned supramolecular polymerizations of monomers to safely remove amyloidogenic proteins in neurodegeneration.}, } @article {pmid40365763, year = {2025}, author = {Cheng, F and Chapman, T and Venturato, J and Davidson, JM and Polido, SA and Rosa-Fernandes, L and San Gil, R and Suddull, HJ and Zhang, S and Macaslam, CY and Szwaja, P and Chung, R and Walker, AK and Rayner, SL and Morsch, M and Lee, A}, title = {Proteomics Analysis of the TDP-43 Interactome in Cellular Models of ALS Pathogenesis.}, journal = {Journal of neurochemistry}, volume = {169}, number = {5}, pages = {e70079}, pmid = {40365763}, issn = {1471-4159}, support = {IG2308//Motor Neurone Disease Research Australia/ ; //FightMND/ ; AL230125//U.S. Department of Defense/ ; }, mesh = {Humans ; *DNA-Binding Proteins/metabolism/genetics ; *Amyotrophic Lateral Sclerosis/metabolism/genetics/pathology ; *Proteomics/methods ; Animals ; Oxidative Stress/physiology ; }, abstract = {Cytoplasmic aggregation and nuclear depletion of TAR DNA-binding protein 43 (TDP-43) is a hallmark pathology of several neurodegenerative diseases including amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration (FTLD) and limbic-predominant age-related TDP-43 encephalopathy (LATE). However, the protein interactome of TDP-43 remains incompletely defined. In this study, we aimed to identify putative TDP-43 protein partners within the nucleus and the cytoplasm and with different disease models of TDP-43 by comparing TDP-43 interaction partners in three different cell lines. We verified the levels of interaction of protein partners under stress conditions as well as after introducing TDP-43 variants containing ALS missense mutations (G294V and A315T). Overall, we identified 58 putative wild-type TDP-43 interactors, including novel binding partners responsible for RNA metabolism and splicing. Oxidative stress exposure broadly led to changes in TDP-43[WT] interactions with proteins involved in mRNA metabolism, suggesting a dysregulation of the transcriptional machinery early in disease. Conversely, although G294V and A315T mutations are both located in the C-terminal domain of TDP-43, both mutants presented different interactome profiles with most interaction partners involved in translational and transcriptional machinery. Overall, by correlating different cell lines and disease-simulating interventions, we provide a list of high-confidence TDP-43 interaction partners, including novel and previously reported proteins. Understanding pathological changes to TDP-43 and its specific interaction partners in different models of stress is critical to better understand TDP-43 proteinopathies and provide novel potential therapeutic targets and biomarkers.}, } @article {pmid40365751, year = {2025}, author = {Connaghan, KP and Eshghi, M and Haenssler, AE and Green, JR and Wang, J and Scheier, Z and Keegan, M and Clark, A and Onnela, JP and Burke, KM and Berry, JD}, title = {A Preliminary Investigation of Acoustic Features for Remote Monitoring of Respiration in ALS.}, journal = {Muscle & nerve}, volume = {}, number = {}, pages = {}, pmid = {40365751}, issn = {1097-4598}, support = {K23 DC019179/DC/NIDCD NIH HHS/United States ; R15DC018944/NH/NIH HHS/United States ; R15 DC018944/DC/NIDCD NIH HHS/United States ; K24DC06312/NH/NIH HHS/United States ; K23DC019179/NH/NIH HHS/United States ; F32DC020896/NH/NIH HHS/United States ; K24 DC016312/DC/NIDCD NIH HHS/United States ; //ALS Association/ ; F32 DC020896/DC/NIDCD NIH HHS/United States ; }, abstract = {INTRODUCTION/AIMS: There is a substantial need to establish reliable approaches for low-burden at-home monitoring of respiratory function for people with amyotrophic lateral sclerosis (PALS). This preliminary study assessed the potential of acoustic features extracted from a smartphone passage reading task to serve as clinically meaningful outcome measures reflecting instrumental and self-reported respiratory function measures.

METHODS: Thirty-six PALS completed an in-clinic slow vital capacity (SVC) task, followed by at-home completion of surveys and audio recording of a reading passage using a smartphone application. Speaking rate and pause features were extracted offline. Correlation analysis evaluated the relationship between the acoustic features and both instrumental (SVC) and self-reported (respiratory subscale of the self-entry version of the ALS Functional Rating Scale-Revised; ALSFRS-RSE) measures of respiratory function. Receiver operator characteristic (ROC) with area under the curve (AUC) analysis evaluated the utility of acoustic features for classifying participants with and without respiratory involvement.

RESULTS: SVC and respiratory self-ratings were significantly correlated with pause, but not rate, measures. Percent pause time was the most strongly correlated acoustic feature with both SVC (r = -0.62) and ALSFRS-RSE respiratory subscale ratings (r = -0.43). ROC analysis revealed that percent pause time classified participants presenting with respiratory involvement based on instrumentation (SVC < 70% predicted [AUC = 0.70]; SVC < 50% predicted [AUC = 0.88]) and self-ratings when using the respiratory ALSFRS-RSE score cut-off of < 11 (AUC = 0.78), but not < 12 (AUC = 0.61).

DISCUSSION: Percent pause time, extracted from a smartphone-recorded passage reading, offers a promising index for remote assessment and monitoring of respiratory function in PALS.}, } @article {pmid40364652, year = {2025}, author = {Gonçalves Netto, A and Ribeiro, VHV and Nicolai, M and Lopez Ovejero, RF and Silva, VFV and Junior, GJP and Brunharo, C}, title = {Genetic diversity and population structure of ALS-resistant Amaranthus hybridus across Brazil's primary soybean-growing regions.}, journal = {Pest management science}, volume = {81}, number = {9}, pages = {5394-5402}, pmid = {40364652}, issn = {1526-4998}, mesh = {*Amaranthus/genetics/drug effects/enzymology ; *Herbicide Resistance/genetics ; Brazil ; *Acetolactate Synthase/antagonists & inhibitors/genetics ; *Genetic Variation ; *Herbicides/pharmacology ; Glycine max/growth & development ; *Plant Proteins/genetics/metabolism/antagonists & inhibitors ; }, abstract = {BACKGROUND: Resistance to acetolactate synthase (ALS)-inhibiting herbicides has emerged in Amaranthus hybridus populations across Brazil's soybean-growing regions. To gain insights into the evolutionary origins and spread of resistance, this study (1) investigated the ALS inhibitor resistance mechanisms in nine A. hybridus populations and (2) assessed their genetic diversity, structure, and relatedness.

RESULTS: Resistance to the ALS inhibitor chlorimuron in A. hybridus was associated with two distinct target-site mutations: Trp-574-Leu and Asp-376-Glu. Population genetics revealed low levels of genetic diversity (HE = 0.00117 to 0.16019; π = 0.00126 to 0.17421) and inbreeding (FIS = 0.0015 to 0.13157). Principal component analysis differentiated A. hybridus by geographical region, while ADMIXTURE analysis revealed population structure with evidence of admixture between genetic clusters in three groups of populations.

CONCLUSION: The results suggest multiple local and independent evolutionary origins of resistance. The spread of resistance is primarily driven by local herbicide selection pressure and gene flow through seed dispersal. © 2025 The Author(s). Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.}, } @article {pmid40364643, year = {2025}, author = {Wen, X and Lan, T and Su, W and Cao, B and Wang, Y and Chen, Y}, title = {Latest progress and challenges in drug development for degenerative motor neuron diseases.}, journal = {Neural regeneration research}, volume = {}, number = {}, pages = {}, doi = {10.4103/NRR.NRR-D-24-01266}, pmid = {40364643}, issn = {1673-5374}, abstract = {Motor neuron diseases are sporadic or inherited fatal neurodegenerative conditions. They selectively affect the upper and/or lower motor neurons in the brain and spinal cord and feature a slow onset and a subacute course contingent upon the site of damage. The main types include amyotrophic lateral sclerosis, progressive muscular atrophy, primary lateral sclerosis, and progressive bulbar palsy, the pathological processes of which are largely identical, with the main disparity lying in the location of the lesions. Amyotrophic lateral sclerosis is the representative condition in this group of diseases, while other types are its variants. Hence, this article mainly focuses on the advancements and challenges in drug research for amyotrophic lateral sclerosis but also briefly addresses several other important degenerative motor neuron diseases. Although the precise pathogenesis remains elusive, recent advancements have shed light on various theories, including gene mutation, excitatory amino acid toxicity, autoimmunology, and neurotrophic factors. The US Food and Drug Administration has approved four drugs for use in delaying the progression of amyotrophic lateral sclerosis: riluzole, edaravone, AMX0035, and tofersen, with the latter being the most recent to receive approval. However, following several phase III trials that failed to yield favorable outcomes, AMX0035 has been voluntarily withdrawn from both the US and Canadian markets. This article presents a comprehensive summary of drug trials primarily completed between January 1, 2023, and June 30, 2024, based on data sourced from clinicaltrials.gov. Among these trials, five are currently in phase I, seventeen are in phase II, and eleven are undergoing phase III evaluation. Notably, 24 clinical trials are now investigating potential disease-modifying therapy drugs, accounting for the majority of the drugs included in this review. Some promising drugs being investigated in preclinical studies, such as ATH-1105, are included in our analysis, and another review in frontiers in gene therapy and immunotherapy has demonstrated their therapeutic potential for motor neuron diseases. This article was written to be an overview of research trends and treatment prospects related to motor neuron disease drugs, with the aim of highlighting the latest potentialities for clinical therapy.}, } @article {pmid40364629, year = {2025}, author = {Sepehrimanesh, M and Xu, W and Ding, B}, title = {Comparative analysis of chemical and lentiviral approaches in the generation of human induced pluripotent stem cell-derived motor neurons.}, journal = {Neural regeneration research}, volume = {}, number = {}, pages = {}, doi = {10.4103/NRR.NRR-D-24-00435}, pmid = {40364629}, issn = {1673-5374}, abstract = {The generation of human induced pluripotent stem cell-derived motor neurons overcomes limited access to human tissues and offers an unprecedented approach to modeling motor neuron diseases such as dystonia and amyotrophic lateral sclerosis. Motor neurons generated through different strategies may exhibit substantial differences in purity, maturation, characterization, and even neuronal identity, leading to variable outcomes in disease modeling and drug screening. However, very few comparative studies have been conducted to determine the similarities and differences among motor neurons prepared via different protocols. In this study, we prepared human induced pluripotent stem cell-motor neurons via lentiviral delivery of transcription factors and chemical induction and performed a systematic comparative analysis. We found that motor neurons generated by both approaches showed typical motor neuron morphology and robustly expressed motor neuron-specific markers, such as nuclear homeobox transcription factor 9 and choline acetyltransferase. The chemical induction protocol utilizes a combination of small molecules to induce motor neuron differentiation, offering a significantly faster maturation time of 35 days compared to 46 days with lentiviral delivery of transcription factors. Additionally, while lentiviral delivery of transcription factors are suitable for downstream biochemical analysis, chemical induction are more applicable for therapeutic approaches as they avoid the use of lentiviruses. Both approaches produce motor neurons with high purity (> 95%) and yield. No significant differences were found between chemical induction and lentiviral delivery of transcription factors in terms of motor neuron markers and maturation markers. These robust methodologies offer researchers powerful tools for investigating motor neuron diseases and potential therapeutic strategies.}, } @article {pmid40364088, year = {2025}, author = {Plotti, F and Martinelli, A and Terranova, C and De Cicco Nardone, C and Montera, R and Luvero, D and Guzzo, F and Di Donato, V and Cundari, GB and Manco, S and Angioli, R}, title = {Laparoscopic Lateral Suspension (LLS) for Pelvic Organ Prolapse (POP): Update and Systematic Review of Prospective and Randomised Trials.}, journal = {Journal of clinical medicine}, volume = {14}, number = {9}, pages = {}, pmid = {40364088}, issn = {2077-0383}, abstract = {Background: Pelvic organ prolapse (POP) significantly impacts women's quality of life, especially in postmenopausal patients. Although laparoscopic sacrocolpopexy (LSC) is the gold standard for advanced apical prolapse, its complexity and risk of complications have led to alternative approaches like laparoscopic lateral suspension (LLS), a minimally invasive technique with promising results. Methods: A comprehensive search using PubMed databases was performed. The search was conducted from June 2024 to September 2024. The search string used was as follows: (pelvic organ prolapse) AND (lateral suspension) OR (laparoscopic lateral suspension). We included randomized controlled trials, prospective cohort studies, prospective observational studies, and case studies. We excluded retrospective studies, small case series, case reports, and articles not published in English. All selected articles were screened based on the titles and abstracts. Relevant data were extracted and tabulated. Results: An overall number of 12 studies were included in our analysis. LLS demonstrated high anatomical success rates: 91.15% for the anterior, 94.95% for the central, and 86.55% for the posterior compartments. The randomized controlled studies exhibit comparable effectiveness between both methods (LLS vs. LSC) and LLS appears to be the best option for anterior repair or anterior-apical repair. Patient satisfaction rates exceeded 90%, with reduced operative times (123 ± 33 min and 193 ± 55.6 min for ALS and ASC, respectively). According to the Claiven-Dindo scale, 0.17% of postoperative complications were graded more than III. The rate of mesh erosion was 0% to 10%. The technique showed particular benefit for uterine preservation and in obese patients but was less effective for severe posterior prolapse. Conclusions: Laparoscopic lateral suspension offers a safe, effective alternative for POP management, with significant anatomical and functional benefits. Its minimally invasive nature, shorter surgery time, and high satisfaction rates make it suitable for tailored patient care. Further studies should standardize evaluation metrics and assess long-term outcomes. The review was not registered. No funding was received. The authors declare no competing interests.}, } @article {pmid40363964, year = {2025}, author = {Niemann, BR and Murthy, J and Breinholt, C and Swords, J and Stevens, A and Garland-Kledzik, M and Mayers, K and Groves, E and Train, K and Murken, D}, title = {Postoperative C-Reactive Protein Trend Is a More Accurate Predictor of Anastomotic Leak than Absolute Values Alone.}, journal = {Journal of clinical medicine}, volume = {14}, number = {9}, pages = {}, pmid = {40363964}, issn = {2077-0383}, abstract = {Background/Objectives: An anastomotic leak (AL) following colorectal surgery is one of the most feared complications due to its associated morbidity and mortality. Early detection of ALs remains difficult, as the development of clinical signs of deterioration can be a late finding. This is particularly problematic in patients with poor access to care after discharge. C-reactive protein (CRP) is a systemic marker of inflammation that has been proposed as an early AL screening. However, absolute cut-off values have been shown to have limited sensitivity and specificity. We propose the use of CRP trends for early AL detection. Methods: A retrospective chart review of patients undergoing surgery requiring at least one anastomosis at a single tertiary care center was performed. Patients with two or fewer postoperative CRP values were excluded. Postoperative CRP trends were compared between control and AL patients using a mixed model with a Geisser-Greenhouse correction. Results: CRP trends differed significantly between AL and control patients, with a 10% CRP increase after postoperative day two showing 100% sensitivity and 84% specificity for an AL as well as a 100% negative predictive value. Accepted CRP cut-off values on postoperative days three and four had sensitivities of only 71.4% and 80% and specificities of 70.0% and 76.5%, respectively. CRP trends differed in AL versus control patients despite the surgical approach or presence of additional procedures. Conclusions: Daily monitoring of CRP trends (versus absolute cut-offs) may enhance early anastomotic leak detection and aid in discharge decision-making, particularly important in rural settings with limited healthcare access.}, } @article {pmid40362907, year = {2025}, author = {Christopher, CJ and Morgan, KH and Tolleson, CM and Trudell, R and Fernandez-Romero, R and Rice, L and Abiodun, BA and Vickery, Z and Jones, KA and Woodall, BM and Nagy, C and Mieczkowski, PA and Bowen, G and Campagna, SR and Ellis, JC}, title = {Specific Bacterial Taxa and Their Metabolite, DHPS, May Be Linked to Gut Dyshomeostasis in Patients with Alzheimer's Disease, Parkinson's Disease, and Amyotrophic Lateral Sclerosis.}, journal = {Nutrients}, volume = {17}, number = {9}, pages = {}, pmid = {40362907}, issn = {2072-6643}, support = {N/A//The Cole Family who support Parkinson's care and research at the Cole Center for Parkinson's Disease and Movement Disorders/ ; N/A//University of Tennessee at Knoxville's Human Health & Wellness Program/ ; N/A//Laboratory Directed Research and Development Program at Oak Ridge National Laboratory, managed by UT-Battelle, LLC, for the U.S. Department of Energy/ ; N/A//A philanthropic donor to ALS research at the University of Tennessee Medical Center/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Parkinson Disease/microbiology/metabolism ; *Alzheimer Disease/microbiology/metabolism ; *Dysbiosis/microbiology ; Male ; Female ; *Amyotrophic Lateral Sclerosis/microbiology/metabolism ; Aged ; Middle Aged ; Feces/microbiology ; *Bacteria/metabolism/classification ; Homeostasis ; Metabolomics ; Case-Control Studies ; }, abstract = {Background: Neurodegenerative diseases (NDDs) are multifactorial disorders frequently associated with gut dysbiosis, oxidative stress, and inflammation; however, the pathophysiological mechanisms remain poorly understood. Methods: Using untargeted mass spectrometry-based metabolomics and 16S sequencing of human stool, we investigated bacterial and metabolic dyshomeostasis in the gut microbiome associated with early disease stages across three NDDs-amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), Parkinson's disease (PD)-and healthy controls (HC). Results: We discovered a previously unrecognized link between a microbial-derived metabolite with an unknown role in human physiology, 2,3-dihydroxypropane-1-sulfonate (DHPS), and gut dysbiosis in NDDs. DHPS was downregulated in AD, ALS, and PD, while bacteria involved in DHPS metabolism, Eubacterium and Desulfovibrio, were increased in all disease cohorts. Additionally, select taxa within the Clostridia class had strong negative correlations to DHPS, suggesting a potential role in DHPS metabolism. A catabolic product of DHPS is hydrogen sulfide, and when in excess, it is known to promote inflammation, oxidative stress, mitochondrial damage, and gut dysbiosis, known hallmarks of NDDs. Conclusions: These findings suggest that cryptic sulfur metabolism via DHPS is a potential missing link in our current understanding of gut dysbiosis associated with NDD onset and progression. As this was a hypothesis generating study, more work is needed to elucidate the role of DHPS in gut dysbiosis and neurodegenerative diseases.}, } @article {pmid40362746, year = {2025}, author = {Moțățăianu, A and Mănescu, IB and Șerban, G and Ion, V and Bălașa, R and Andone, S}, title = {The Effects of a Mediterranean Diet on Metabolic Hormones and Cytokines in Amyotrophic Lateral Sclerosis Patients: A Prospective Interventional Study.}, journal = {Nutrients}, volume = {17}, number = {9}, pages = {}, pmid = {40362746}, issn = {2072-6643}, support = {PN-III-P1-1.1-TE-2021-0960//Ministry of Research, Innovation and Digitization, CNCS - UEFISCDI/ ; }, mesh = {Humans ; *Diet, Mediterranean ; *Amyotrophic Lateral Sclerosis/diet therapy/blood ; Male ; Female ; Prospective Studies ; Middle Aged ; *Cytokines/blood ; Aged ; Leptin/blood ; Glucagon-Like Peptide 1/blood ; Insulin/blood ; Disease Progression ; *Gastrointestinal Hormones/blood ; }, abstract = {Background: Amyotrophic lateral sclerosis (ALS) is a prevalent neurodegenerative disease but lacks effective treatments. Dietary interventions, notably the Mediterranean diet, promise to modulate disease pathways. This study aimed to investigate the impact of the Mediterranean diet on gut hormones and cytokines in patients with amyotrophic lateral sclerosis (ALS). Methods: We conducted a 12-month, single-center prospective study on a total of 44 ALS patients. After a 6-month observation period, the patients were placed on a dairy-free Mediterranean diet for the next 6 months. We evaluated the patients at baseline (T0), 6 months (T1), and 12 months (T2). We measured the ALS Functional Rating Scale-Revised (ALSFRS-R) scores and a panel of metabolic hormones and cytokines. Results: The ALSFRS-R scores declined over 12 months (37.59 ± 6.32 at T0 vs. 30.23 ± 8.91 at T2, p < 0.001), indicating expected disease progression with no significant difference in the rate of decline before and after the dietary intervention. The leptin levels significantly decreased from T0 to T1 (T0: 4956 ± 3994 pg/mL vs. T1: 3196 ± 2807 pg/mL, p = 0.038). The insulin and GLP-1 levels showed significant drops at T2 (insulin T0: 480 ± 369 vs. T2: 214 ± 213 pmol/L, p < 0.01; GLP-1 T0: 118 ± 76 vs. T2: 60 ± 57 pg/mL, p < 0.01). C-peptide increased at T2 (T0: 3814 ± 1967 vs. T2: 9532 ± 4000 pg/mL, p < 0.001). Among the cytokines, the levels of IL-12P70, IL-13, IL-9, and IL-2 significantly decreased from T0 to T2 (all p < 0.05), while IL-17A and TNFα significantly increased between T1 and T2 (p < 0.01). Conclusions: The Mediterranean diet intervention in ALS patients modulated several metabolic hormones and cytokines but with no evidence of impacting the disease's evolution or of a slowed clinical progression. These findings suggest a potential role for dietary intervention, particularly the Mediterranean diet, in modulating gut hormones and cytokines in ALS patients, but its impact on disease course is unclear. Future randomized studies are needed to confirm these changes and to determine whether dietary intervention can have any benefit in ALS.}, } @article {pmid40362586, year = {2025}, author = {Zhang, R and Azhir, A and McGrath, MS}, title = {Respiratory Function Improvement and Lifespan Extension Following Immunotherapy with NP001 Support the Concept That Amyotrophic Lateral Sclerosis (ALS) Is an Immuno-Neurologic Disease.}, journal = {International journal of molecular sciences}, volume = {26}, number = {9}, pages = {}, pmid = {40362586}, issn = {1422-0067}, support = {Neuvivo-NP001//Neuvivo, Inc./ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/immunology/drug therapy/physiopathology/mortality/therapy ; Middle Aged ; Male ; Female ; Aged ; *Immunotherapy/methods ; Body Mass Index ; Adult ; Vital Capacity/drug effects ; Immunity, Innate/drug effects ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a heterogeneous disease that involves progressive loss of voluntary muscle and ultimately, respiratory function, which is the primary cause of death in ALS patients. Respiratory vital capacity (VC) measurements are objective, reproducible, and directly related to survival. Respiratory function is known to be negatively affected in individuals with excess abdominal fat contributing to a chronic innate immune inflammatory state. To test whether ALS patients might have a body mass index (BMI) related VC response to the innate immune system regulator NP001, clinical results from two NP001 phase 2 trials were evaluated in an intent-to-treat manner, stratified by BMI measurements. Slowing of progressive VC loss and extension of overall survival (OS) occurred primarily in ALS patients who were overweight with a BMI ≥ 25 (70% of patients in the phase 2 trials). Innate immune dysfunction is a characteristic of ALS patients ≤ 65 years of age, and in this group both VC and OS changes in response to NP001 were most significant. This study represents a novel approach to ALS, wherein VC and OS were both significantly improved through immunologic, not neurologic modulation with NP001, a precursor to the dominant regulator of inflammation, taurine chloramine.}, } @article {pmid40362582, year = {2025}, author = {Kitaoka, Y and Uchihashi, T and Kawata, S and Nishiura, A and Yamamoto, T and Hiraoka, SI and Yokota, Y and Isomura, ET and Kogo, M and Tanaka, S and Spigelman, I and Seki, S}, title = {Role and Potential of Artificial Intelligence in Biomarker Discovery and Development of Treatment Strategies for Amyotrophic Lateral Sclerosis.}, journal = {International journal of molecular sciences}, volume = {26}, number = {9}, pages = {}, pmid = {40362582}, issn = {1422-0067}, support = {24K13154//Japan Society for the Promotion of Science/ ; 21K10091//Japan Society for the Promotion of Science/ ; 24K13113//Japan Society for the Promotion of Science/ ; 23K09351//Japan Society for the Promotion of Science/ ; 24K13112//Japan Society for the Promotion of Science/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/therapy/diagnosis/metabolism ; Humans ; *Biomarkers/metabolism ; *Artificial Intelligence ; Proteomics/methods ; Neuroimaging/methods ; Deep Learning ; }, abstract = {Neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), present significant challenges owing to their complex pathologies and a lack of curative treatments. Early detection and reliable biomarkers are critical but remain elusive. Artificial intelligence (AI) has emerged as a transformative tool, enabling advancements in biomarker discovery, diagnostic accuracy, and therapeutic development. From optimizing clinical-trial designs to leveraging omics and neuroimaging data, AI facilitates understanding of disease and treatment innovation. Notably, technologies such as AlphaFold and deep learning models have revolutionized proteomics and neuroimaging, offering unprecedented insights into ALS pathophysiology. This review highlights the intersection of AI and ALS, exploring the current state of progress and future therapeutic prospects.}, } @article {pmid40362512, year = {2025}, author = {Chong, ZZ and Souayah, N}, title = {Targeting Gene C9orf72 Pathogenesis for Amyotrophic Lateral Sclerosis.}, journal = {International journal of molecular sciences}, volume = {26}, number = {9}, pages = {}, pmid = {40362512}, issn = {1422-0067}, mesh = {*C9orf72 Protein/genetics/metabolism ; *Amyotrophic Lateral Sclerosis/genetics/pathology/metabolism/therapy ; Humans ; DNA Repeat Expansion ; Animals ; Mutation ; Autophagy ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal adult neurodegenerative disorder. Since no cure has been found, finding effective therapeutic targets for ALS remains a major challenge. Gene C9orf72 mutations with the formation of hexanucleotide repeat (GGGGCC) expansion (HRE) have been considered the most common genetic pathogenesis of ALS. The literature review indicates that the C9orf72 HRE causes both the gain-of-function toxicity and loss of function of C9ORF72. The formation of RNA foci and dipeptide repeats (DPRs) resulting from HRE is responsible for toxic function gain. The RNA foci can interfere with RNA processing, while DPRs directly bind to and sequester associated proteins to disrupt processes of rRNA synthesis, mRNA translation, autophagy, and nucleocytoplasmic transport. The mutations of C9orf72 and HRE result in the loss of functional C9ORF72. Under physiological conditions, C9ORF72 binds to Smith-Magenis chromosome region 8 and WD repeat-containing protein and forms a protein complex. Loss of C9ORF72 leads to autophagic impairment, increased oxidative stress, nucleocytoplasmic transport impairment, and inflammatory response. The attempted treatments for ALS have been tried by targeting C9orf72 HRE; however, the outcomes are far from satisfactory yet. More studies should be performed on pharmacological and molecular modulators against C9orf72 HRE to evaluate their efficacy by targeting HRE.}, } @article {pmid40362464, year = {2025}, author = {Yapici, I and Tokur, AG and Sever, B and Ciftci, H and Basak, AN and DeMirci, H}, title = {Structural Insights into the Dynamics of Water in SOD1 Catalysis and Drug Interactions.}, journal = {International journal of molecular sciences}, volume = {26}, number = {9}, pages = {}, pmid = {40362464}, issn = {1422-0067}, support = {122Z429//Scientific and Technological Research Council of Turkey (TÜBİTAK)/ ; 101061939//European Union's Horizon Europe research and innovation programme under the Marie Sktodowska-Curie grant agreement/ ; }, mesh = {*Superoxide Dismutase-1/chemistry/metabolism/antagonists & inhibitors/genetics ; *Water/chemistry/metabolism ; Humans ; Molecular Docking Simulation ; Catalytic Domain ; Hydrogen Bonding ; Catalysis ; Molecular Dynamics Simulation ; Amyotrophic Lateral Sclerosis/drug therapy ; Crystallography, X-Ray ; Protein Conformation ; }, abstract = {Superoxide dismutase 1 (SOD1) is a crucial enzyme that protects cells from oxidative damage by converting superoxide radicals into H2O2 and O2. This detoxification process, essential for cellular homeostasis, relies on a precisely orchestrated catalytic mechanism involving the copper cation, while the zinc cation contributes to the structural integrity of the enzyme. This study presents the 2.3 Å crystal structure of human SOD1 (PDB ID: 9IYK), revealing an assembly of six homodimers and twelve distinct active sites. The water molecules form a complex hydrogen-bonding network that drives proton transfer and sustains active site dynamics. Our structure also uncovers subtle conformational changes that highlight the intrinsic flexibility of SOD1, which is essential for its function. Additionally, we observe how these dynamic structural features may be linked to pathological mutations associated with amyotrophic lateral sclerosis (ALS). By advancing our understanding of hSOD1's mechanistic intricacies and the influence of water coordination, this study offers valuable insights for developing therapeutic strategies targeting ALS. Our structure's unique conformations and active site interactions illuminate new facets of hSOD1 function, underscoring the critical role of structural dynamics in enzyme catalysis. Moreover, we conducted a molecular docking analysis using SOD1 for potential radical scavengers and Abelson non-receptor tyrosine kinase (c-Abl, Abl1) inhibitors targeting misfolded SOD1 aggregation along with oxidative stress and apoptosis, respectively. The results showed that CHEMBL1075867, a free radical scavenger derivative, showed the most promising docking results and interactions at the binding site of hSOD1, highlighting its promising role for further studies against SOD1-mediated ALS.}, } @article {pmid40362304, year = {2025}, author = {Shiryaeva, O and Tolochko, C and Alekseeva, T and Dyachuk, V}, title = {Targets and Gene Therapy of ALS (Part 1).}, journal = {International journal of molecular sciences}, volume = {26}, number = {9}, pages = {}, pmid = {40362304}, issn = {1422-0067}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy/genetics/pathology ; *Genetic Therapy/methods ; Animals ; Superoxide Dismutase-1/genetics ; C9orf72 Protein/genetics ; Mutation ; Gene Editing ; RNA-Binding Protein FUS/genetics ; Oligonucleotides, Antisense/therapeutic use ; CRISPR-Cas Systems ; DNA-Binding Proteins/genetics ; RNA Interference ; MicroRNAs/genetics ; Disease Models, Animal ; RNA, Small Interfering/genetics ; Motor Neurons/metabolism/pathology ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the selective death of motor neurons, which causes muscle atrophy. Genetic forms of ALS are recorded only in 10% of cases. However, over the past decade, studies in genetics have substantially contributed to our understanding of the molecular mechanisms underlying ALS. The identification of key mutations such as SOD1, C9orf72, FUS, and TARDBP has led to the development of targeted therapy that is gradually being introduced into clinical trials, opening up a broad range of opportunities for correcting these mutations. In this review, we aimed to present an extensive overview of the currently known mechanisms of motor neuron degeneration associated with mutations in these genes and also the gene therapy methods for inhibiting the expression of their mutant proteins. Among these, antisense oligonucleotides, RNA interference (siRNA and miRNA), and gene-editing (CRISPR/Cas9) methods are of particular interest. Each has shown its efficacy in animal models when targeting mutant genes, whereas some of them have proven to be efficient in human clinical trials.}, } @article {pmid40360341, year = {2025}, author = {Lin, W and Huang, C and Tan, Z and Xu, H and Wei, W and Wang, L}, title = {Cu[II]-bis(thioureido) Complex: A Potential Radiotracer for Detecting Oxidative Stress and Neuroinflammation in Neurodegenerative Diseases.}, journal = {Seminars in nuclear medicine}, volume = {55}, number = {4}, pages = {577-586}, doi = {10.1053/j.semnuclmed.2025.03.008}, pmid = {40360341}, issn = {1558-4623}, mesh = {Humans ; *Oxidative Stress ; *Neurodegenerative Diseases/diagnostic imaging/metabolism/complications ; Animals ; *Copper/chemistry ; *Neuroinflammatory Diseases/diagnostic imaging/metabolism/complications ; Positron-Emission Tomography ; Radioactive Tracers ; *Thiosemicarbazones/chemistry ; }, abstract = {Neurodegenerative diseases, characterized by progressive neuronal degeneration and associated with neuroinflammation and oxidative stress, present significant challenges in diagnosis and treatment. This review explores the potential of copper(II)-bis(thiosemicarbazone) complexes, particularly Cu-ATSM, as a dual-purpose radiopharmaceutical for imaging and therapeutic interventions. Cu-ATSM exhibits unique redox-dependent retention in pathological microenvironments, driven by mitochondrial dysfunction and hyper-reductive states, which enables the noninvasive detection of oxidative stress via positron emission tomography (PET). Preclinical studies demonstrate its efficacy in mitigating neuroinflammation by suppressing glial activation, reducing the secretion of pro-inflammatory cytokines (e.g., TNF-α, MCP-1), and increasing the expression of neuroprotective metallothionein-1 (MT1). Some Clinical research reveals elevated [64]Cu-ATSM uptake in Parkinson's disease (PD), Alzheimer's disease (AD), and amyotrophic lateral sclerosis (ALS) patients, correlating with disease severity and regional oxidative stress markers. Furthermore, Cu-ATSM derivatives show promise in modulating blood-brain barrier (BBB) permeability, enhancing amyloid-β clearance, and restoring copper homeostasis in ALS models. Despite these advances, limitations such as small cohort sizes and heterogeneity in clinical studies underscore the need for larger-scale validation. Multimodal imaging integrating PET and MRI, alongside novel structural analogs targeting Aβ plaques and redox imbalances, emerges as a strategic direction for future research. Collectively, Cu-ATSM represents a transformative tool for elucidating neuropathological mechanisms and advancing therapeutic strategies in neurodegenerative disorders.}, } @article {pmid40360159, year = {2025}, author = {Li, Z and Li, Y and Zhao, J and Zhang, F and Dang, W and Jia, Y and Guo, F and Guo, L}, title = {Association among blood pressure, antihypertensive drugs, and amyotrophic lateral sclerosis.}, journal = {Arquivos de neuro-psiquiatria}, volume = {83}, number = {5}, pages = {1-8}, pmid = {40360159}, issn = {1678-4227}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/etiology/prevention & control ; *Antihypertensive Agents/therapeutic use ; *Blood Pressure/drug effects/genetics ; Mendelian Randomization Analysis ; Genome-Wide Association Study ; *Hypertension/drug therapy/genetics/complications ; Risk Factors ; Male ; Angiotensin-Converting Enzyme Inhibitors/therapeutic use ; Female ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a fatal and incurable neurodegenerative disease. The impacts of antihypertensive drugs and blood pressure (BP) on ALS are currently debatable.

OBJECTIVE:  To evaluate the causal relationship involving antihypertensive drugs, BP, and ALS through a Mendelian randomization (MR) analysis.

METHODS:  The causal relationship between BP and ALS was evaluated by a bidirectional two-sample MR analysis. Then, a sensitivity analysis was performed using a secondary BP genome-wide association study. The drug-target MR was employed to evaluate the impact of antihypertensive drugs on ALS. Furthermore, we used cis-expression quantitative trait loci (cis-eQTLs) data from brain tissue and blood to validate the positive results by a summary-based MR method.

RESULTS:  We found that an increment in systolic BP (SBP) could elevate the risk of ALS (inverse-variance weighted [IVW] odds ratio [OR] = 1.003; 95% confidence interval [95%CI]: 1.001-1.006; per 10-mmHg increment) and ALS might be protected by angiotensin-converting enzyme inhibitors (ACEIs; OR = 0.970; 95%CI: 0.956-0.984; p = 1.96 × 10[-5]; per 10-mmHg decrement). A causal relationship was not observed between diastolic BP and other antihypertensive drugs in ALS.

CONCLUSION:  In the present study, genetic support for elevated SBP serves as a risk factor for ALS. Besides, ACEIs hold promise as a candidate for ALS.}, } @article {pmid40358451, year = {2025}, author = {Rahsepar, AA and Bedayat, A}, title = {Beyond Spirometry: AI-Driven Chest CT Analysis, a New Frontier in Monitoring Amyotrophic Lateral Sclerosis.}, journal = {Radiology}, volume = {315}, number = {2}, pages = {e250988}, doi = {10.1148/radiol.250988}, pmid = {40358451}, issn = {1527-1315}, } @article {pmid40358443, year = {2025}, author = {Choi, SJ and Kim, JS and Jeong, SY and Son, H and Sung, JJ and Park, CM and Choi, KS}, title = {Association of Deep Learning-based Chest CT-derived Respiratory Parameters with Disease Progression in Amyotrophic Lateral Sclerosis.}, journal = {Radiology}, volume = {315}, number = {2}, pages = {e243463}, doi = {10.1148/radiol.243463}, pmid = {40358443}, issn = {1527-1315}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnostic imaging/physiopathology/mortality ; Male ; Female ; Retrospective Studies ; Aged ; *Deep Learning ; Disease Progression ; *Tomography, X-Ray Computed/methods ; Middle Aged ; Vital Capacity ; Lung/diagnostic imaging/physiopathology ; Respiratory Muscles/diagnostic imaging/physiopathology ; }, abstract = {Background Forced vital capacity (FVC) is a standard measure of respiratory function in patients with amyotrophic lateral sclerosis (ALS) but has limitations, particularly for patients with bulbar impairment. Purpose To determine the value of deep learning-based chest CT-derived respiratory parameters in predicting ALS progression and survival. Materials and Methods This retrospective study included patients with ALS diagnosed between January 2010 and July 2023 who underwent chest CT at a tertiary hospital. Deep learning-based software was used to measure lung and respiratory muscle volume, normalized for height as the lung volume index (LVI) and respiratory muscle index (RMI). Differences in these parameters across King clinical stages were assessed using ordinal logistic regression. Tracheostomy-free survival was evaluated using Cox regression and time-dependent receiver operating characteristic analysis. Subgroup analysis was conducted for patients with bulbar impairment. In addition, a Gaussian process regressor model was developed to estimate FVC based on lung volume, respiratory muscle volume, age, and sex. Results A total of 261 patients were included in the study (mean age, 65.2 years ± 11.9 [SD]; 156 male patients). LVI and RMI decreased with increasing King stage (both P < .001). The high LVI and high RMI groups had better survival (both P < .001). After adjustment, LVI (hazard ratio [HR] = 0.998 [95% CI: 0.996, 1.000]; P = .021) and RMI (HR = 0.992 [95% CI: 0.988, 0.996]; P < .001) remained independent prognostic factors. In patients with bulbar impairment, LVI (HR = 0.998 [95% CI: 0.996, 1.000]; P = .029) and RMI (HR = 0.991 [95% CI: 0.987, 0.996]; P < .001) were independent prognostic factors. Time-dependent receiver operating characteristic curve analysis revealed no significant differences in survival prediction performance among LVI, RMI, and FVC. The Gaussian process regressor model estimated FVC with approximately 8% error. Conclusion The deep learning-derived CT metrics LVI and RMI reflected ALS stage, enabled FVC prediction, and supported assessment in patients with limited respiratory function. © RSNA, 2025 Supplemental material is available for this article. See also the editorial by Rahsepar and Bedayat in this issue.}, } @article {pmid40356623, year = {2025}, author = {Mori, S and Zhou, H and Omura, T and Tsumoto, H and Miura, Y and Shigemoto, K}, title = {Muscle-specific kinase levels in blood are an early diagnostic biomarker for SOD1-93A mouse model of ALS.}, journal = {Frontiers in neurology}, volume = {16}, number = {}, pages = {1556120}, pmid = {40356623}, issn = {1664-2295}, abstract = {Neuromuscular junction (NMJ) denervation is an early event preceding motor neuron loss in amyotrophic lateral sclerosis (ALS). Progressive loss of the NMJ leads to irreversible muscle weakness and atrophy. Muscle-specific kinase (MuSK), locally expressed at the postsynaptic membrane of the NMJ, is activated by agrin released from motor nerve terminals and is essential for NMJ maintenance and regeneration. Here, we found that the progression of NMJ denervation prior to the onset of muscle weakness in SOD1-93A mouse model of ALS correlated with increased serum MuSK immunoreactivity and elevated MuSK expression throughout the skeletal muscle. Our results suggest that neuromuscular failure associated with the onset of muscle weakness increases MuSK expression throughout the muscle, which is subsequently cleaved by proteolytic enzymes to increase MuSK immunoreactivity in the blood. These results demonstrate that the level of serum MuSK immunoreactivity may indicate the early phase of NMJ denervation and serve as a biomarker for assessing the progression of other types of ALS and therapeutic benefits in preclinical studies.}, } @article {pmid40355776, year = {2025}, author = {Hirose, S and Kobatake, Y and Tada, N and Kandeel, M and Itoh, A and Oh-Hashi, K}, title = {NanoBiT-based Analysis of Canine SOD1 Protein Dynamics: Understanding the Role of CCS and Ebselen Derivatives as Potential Therapeutics for Canine Degenerative Myelopathy.}, journal = {Cell biochemistry and biophysics}, volume = {}, number = {}, pages = {}, pmid = {40355776}, issn = {1559-0283}, support = {KFU241899//Deanship of Scientific Research, Vice Presidency for Graduate Studies and Scientific Research, King Faisal University/ ; }, abstract = {Canine degenerative myelopathy (DM) is a progressive neurodegenerative disorder that shares common pathological features with amyotrophic lateral sclerosis (ALS) in humans. Both diseases are linked to mutations in the superoxide dismutase 1 (SOD1) gene. Understanding the molecular differences between wild-type (WT) and mutant SOD1 proteins is critical for developing therapeutic strategies. In this study, we employed the NanoLuc complementation (NanoBiT) reporter system to investigate the expression and functional differences between WT and E40K mutant canine SOD1 to assess the therapeutic potential of copper chaperone for SOD1 (CCS) and ebselen derivatives. E40K cSOD1 displayed significantly reduced luciferase activity compared to WT cSOD1 in all NanoBiT-tagged combinations, indicating altered homodimerization and protein stability. Co-transfection with CCS increased both WT and mutant cSOD1 protein levels and reporter activities, with a more pronounced effect on the E40K mutant. Ebselen treatment enhanced luciferase activity, particularly in E40K cSOD1-expressing cells. Two compounds (compounds 2 and 5) were stronger than the parent compound in improving mutant cSOD1-derived NanoBiT activities. Additionally, molecular docking simulations revealed stronger binding affinities of ebselen and its derivatives to E40K cSOD1, suggesting potential therapeutic benefits. In conclusion, the NanoLuc reporter system offers a valuable tool for screening potential therapeutics for SOD1-linked neurodegenerative diseases. CCS and ebselen derivatives exhibited promising effects on SOD1 activity, providing a basis for future therapeutic strategies targeting both DM and ALS.}, } @article {pmid40355001, year = {2025}, author = {Ognard, J and El Hajj, G and Verma, O and Ghozy, S and Kadirvel, R and Kallmes, DF and Brinjikji, W}, title = {Advances in endovascular brain computer interface: Systematic review and future implications.}, journal = {Journal of neuroscience methods}, volume = {420}, number = {}, pages = {110471}, doi = {10.1016/j.jneumeth.2025.110471}, pmid = {40355001}, issn = {1872-678X}, mesh = {*Brain-Computer Interfaces/trends ; Animals ; Humans ; *Endovascular Procedures/methods/trends ; *Brain/physiology ; Electrodes, Implanted ; }, abstract = {BACKGROUND: Brain-computer interfaces (BCIs) translate neural activity into real-world commands. While traditional invasive BCIs necessitate craniotomy, endovascular BCIs offer a minimally invasive alternative using the venous system for electrode placement.

NEW METHOD: This systematic review evaluates the technical feasibility, safety, and clinical outcomes of endovascular BCIs, discussing their future implications. A systematic review was conducted per PRISMA guidelines. The search spanned PubMed, Web of Science, and Scopus databases using keywords related to neural interfaces and endovascular approaches. Studies were included if they reported on endovascular BCIs in preclinical or clinical settings. Dual independent screening and extraction focused on electrode material, recording capabilities, safety parameters, and clinical efficacy.

RESULTS: From 1385 initial publications, 26 met the inclusion criteria. Seventeen studies investigated the Stentrode device. Among the 24 preclinical studies, 16 used ovine or rodent models, and 9 addressed engineering or simulation aspects. Two clinical studies reported six ALS patients successfully using an endovascular BCI for digital communication. Preclinical data established the endovascular ovine model, demonstrating stable neural recordings and vascular changes with long-term implantation. Key challenges include thrombosis risk, long-term electrode stability, and anatomical variability.

Endovascular BCI reduced invasiveness, improved safety profiles, with comparable neural recording fidelity to invasive methods, and promising preliminary clinical outcomes in severely paralyzed patients.

CONCLUSIONS: Early results are promising, but clinical data remain scarce. Further research is needed to optimize signal processing, enhance electrode biocompatibility, and refine endovascular procedures for broader clinical applications.}, } @article {pmid40354800, year = {2025}, author = {Benatar, M and McDermott, MP}, title = {Examining the evidence for IL-2 in amyotrophic lateral sclerosis.}, journal = {Lancet (London, England)}, volume = {405}, number = {10492}, pages = {1793-1795}, doi = {10.1016/S0140-6736(25)00901-8}, pmid = {40354800}, issn = {1474-547X}, } @article {pmid40354799, year = {2025}, author = {Bensimon, G and Leigh, PN and Tree, T and Malaspina, A and Payan, CA and Pham, HP and Klaassen, P and Shaw, PJ and Al Khleifat, A and Amador, MDM and Attarian, S and Bell, SM and Beltran, S and Bernard, E and Camu, W and Corcia, P and Corvol, JC and Couratier, P and Danel, V and Debs, R and Desnuelle, C and Dimitriou, A and Ealing, J and Esselin, F and Fleury, MC and Gorrie, GH and Grapperon, AM and Hesters, A and Juntas-Morales, R and Kolev, I and Lautrette, G and Le Forestier, N and McDermott, CJ and Pageot, N and Salachas, F and Sharma, N and Soriani, MH and Sreedharan, J and Svahn, J and Verber, N and Verschueren, A and Yildiz, O and Suehs, CM and Saker-Delye, S and Muller, C and Masseguin, C and Hajduchova, H and Kirby, J and Garlanda, C and Locati, M and Zetterberg, H and Asselain, B and Al-Chalabi, A and , }, title = {Efficacy and safety of low-dose IL-2 as an add-on therapy to riluzole (MIROCALS): a phase 2b, double-blind, randomised, placebo-controlled trial.}, journal = {Lancet (London, England)}, volume = {405}, number = {10492}, pages = {1837-1850}, doi = {10.1016/S0140-6736(25)00262-4}, pmid = {40354799}, issn = {1474-547X}, mesh = {Humans ; Female ; Male ; *Riluzole/administration & dosage/therapeutic use/adverse effects ; Middle Aged ; Double-Blind Method ; *Amyotrophic Lateral Sclerosis/drug therapy/mortality ; Adult ; Aged ; *Interleukin-2/administration & dosage/adverse effects/therapeutic use ; *Neuroprotective Agents/administration & dosage/therapeutic use/adverse effects ; Treatment Outcome ; Drug Therapy, Combination ; Young Adult ; Adolescent ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a life-threatening disease characterised by progressive loss of motor neurons with few therapeutic options. The MIROCALS study tested the hypothesis that low-dose interleukin-2 (IL-2LD) improves survival and function in ALS.

METHODS: In this randomised, double-blind, placebo-controlled trial, male and female riluzole-naive participants, with either a possible, laboratory-supported probable, probable, or definite ALS diagnosis (revised El Escorial criteria), aged 18-76 years, with symptom duration of 24 months or fewer, and slow vital capacity of 70% or more, underwent a riluzole-only 12-18 week run-in period before randomisation in a 1:1 ratio to either 2 million international units (MIU) IL-2LD or placebo by subcutaneous injection daily for 5 days every 28 days over 18 months. The primary endpoint was survival at 640 days (21 months). Secondary outcomes included safety, ALS Functional Rating Scale-Revised (ALSFRS-R) score, and biomarker measurements including regulatory T-cells (Tregs), cerebrospinal fluid (CSF)-phosphorylated-neurofilament heavy-chain (CSF-pNFH), and plasma and CSF-chemokine ligand 2 (CCL2). The primary endpoint analysis used unadjusted log-rank and Cox's model adjusted analyses using pre-defined prognostic covariates to control for the disease and treatment response heterogeneity. The study was 80% powered to detect a two-fold decrease in the risk of death by the log-rank test in the intention-to-treat (ITT) population, including all randomly allocated participants. MIROCALS is registered with ClinicalTrials.gov (NCT03039673) and is complete.

FINDINGS: From June 19, 2017, to Oct 16, 2019, 304 participants were screened, of whom 220 (72%) met all criteria for random allocation after the 12-to-18-week run-in period on riluzole. 136 (62%) of participants were male and 84 participants (38%) were female. 25 (11%) of the 220 randomly allocated participants were defined as having possible ALS under El Escorial criteria. At the cutoff date there was no loss to follow-up, and all 220 patients who were randomly allocated were documented as either deceased (90 [41%]) or alive (130 [59%]), so all participants were included in the ITT and safety populations. The primary endpoint unadjusted analysis showed a non-significant 19% decrease in risk of death with IL-2LD (hazard ratio 0·81 [95% CI 0·54-1·22], p=0·33), failing to demonstrate the expected two-fold decrease in risk of death. The analysis of the primary endpoint adjusted on prognostic covariates, all measured at time of random allocation, showed a significant decrease of the risk of death with IL-2LD (0·32 [0·14-0·73], p=0·007), with a significant treatment by CSF-pNFH interaction (1·0003 [1·0001-1·0005], p=0·001). IL-2LD was safe, and significantly increased Tregs and decreased plasma-CCL2 at all timepoints. Stratification on CSF-pNFH levels measured at random allocation showed that IL-2LD was associated with a significant 48% decrease in risk of death (0·52 [0·30-0·89], p=0·016) in the 70% of the population with low (750-3700 pg/mL) CSF-pNFH levels, while in the 21% with high levels (>3700 pg/mL), there was no significant difference (1·37 [0·68-2·75], p=0·38).

INTERPRETATION: With this treatment schedule, IL-2LD resulted in a non-significant reduction in mortality in the primary unadjusted analysis. However, the difference between the results of unadjusted and adjusted analyses of the primary endpoint emphasises the importance of controlling for disease heterogeneity in ALS randomised controlled trials. The decrease in risk of death achieved by IL-2LD therapy in the trial population with low CSF-pNFH levels requires further investigation of the potential benefit of this therapy in ALS.

FUNDING: European Commission H2020 Programme; French Health Ministry PHRC2014; and Motor Neurone Disease Association.}, } @article {pmid40354780, year = {2025}, author = {Delivoria, DC and Konia, E and Matis, I and Skretas, G}, title = {Optimization of a High-Throughput Screen for Monitoring Disease-Associated Protein Misfolding and Aggregation in Bacteria.}, journal = {ACS synthetic biology}, volume = {14}, number = {6}, pages = {2283-2293}, pmid = {40354780}, issn = {2161-5063}, mesh = {Humans ; *Escherichia coli/metabolism/genetics ; Protein Folding ; *High-Throughput Screening Assays/methods ; Green Fluorescent Proteins/genetics/metabolism ; Protein Aggregates ; Tumor Suppressor Protein p53/genetics/metabolism ; Superoxide Dismutase-1/genetics/metabolism ; Amyloid beta-Peptides/metabolism/genetics ; }, abstract = {Protein misfolding and aggregation are central features of a wide range of diseases, including neurodegenerative disorders, systemic amyloidoses, and cancer. The identification of compounds that can modulate protein folding and aggregation is a key step toward developing effective therapies. High-throughput screening methods are essential for efficiently identifying such compounds. In this study, we optimized a previously developed high-throughput genetic screen for monitoring protein misfolding and aggregation in bacteria. This system is based on monitoring the fluorescence of Escherichia coli cells expressing fusions of human misfolding-prone and disease-related proteins (MisPs) with the green fluorescent protein. We systematically tested a variety of experimental conditions, such as overexpression conditions and MisP-GFP fusion formats, to identify key parameters that affect the sensitivity and dynamic range of the assay. Using misfolding-prone, cancer-associated variants of human p53 as a model system, we found that strong overexpression conditions, such as high copy number vectors, strong promoters, high inducer concentrations, and high overexpression temperatures, can yield optimal assay performance. These optimized assay conditions were also validated with additional MisPs, such as the Alzheimer's disease-associated amyloid-β peptide and variants of superoxide dismutase 1 associated with amyotrophic lateral sclerosis. At the same time, we observed that certain conditions, such as inducer concentrations and overexpression temperature, may need to be precisely fine-tuned for each new MisP target to yield optimal assay performance. Our findings provide a framework for standardizing MisP-GFP screening assays, facilitating their broad application in the discovery of therapeutic agents targeting protein misfolding and aggregation.}, } @article {pmid40353906, year = {2025}, author = {Kleinerova, J and Querin, G and Pradat, PF and Siah, WF and Bede, P}, title = {New developments in imaging in ALS.}, journal = {Journal of neurology}, volume = {272}, number = {6}, pages = {392}, pmid = {40353906}, issn = {1432-1459}, support = {JPND-Cofund-2-2019-1/HRBI_/Health Research Board/Ireland ; HRB EIA-2017-019/HRBI_/Health Research Board/Ireland ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnostic imaging/physiopathology/pathology ; *Neuroimaging/methods/trends ; *Brain/diagnostic imaging ; Magnetic Resonance Imaging ; }, abstract = {Neuroimaging in ALS has contributed considerable academic insights in recent years demonstrating genotype-specific topological changes decades before phenoconversion and characterising longitudinal propagation patterns in specific phenotypes. It has elucidated the radiological underpinnings of specific clinical phenomena such as pseudobulbar affect, apathy, behavioural change, spasticity, and language deficits. Academic concepts such as sexual dimorphism, motor reserve, cognitive reserve, adaptive changes, connectivity-based propagation, pathological stages, and compensatory mechanisms have also been evaluated by imaging. The underpinnings of extra-motor manifestations such as cerebellar, sensory, extrapyramidal and cognitive symptoms have been studied by purpose-designed imaging protocols. Clustering approaches have been implemented to uncover radiologically distinct disease subtypes and machine-learning models have been piloted to accurately classify individual patients into relevant diagnostic, phenotypic, and prognostic categories. Prediction models have been developed for survival in symptomatic patients and phenoconversion in asymptomatic mutation carriers. A range of novel imaging modalities have been implemented and 7 Tesla MRI platforms are increasingly being used in ALS studies. Non-ALS MND conditions, such as PLS, SBMA, and SMA, are now also being increasingly studied by quantitative neuroimaging approaches. A unifying theme of recent imaging papers is the departure from describing focal brain changes to focusing on dynamic structural and functional connectivity alterations. Progressive cortico-cortical, cortico-basal, cortico-cerebellar, cortico-bulbar, and cortico-spinal disconnection has been consistently demonstrated by recent studies and recognised as the primary driver of clinical decline. These studies have led the reconceptualisation of ALS as a "network" or "circuitry disease".}, } @article {pmid40353466, year = {2025}, author = {Dhasmana, S and Dhasmana, A and Khan, S and Narula, AS and Haque, S and Yallapu, MM and Chauhan, SC}, title = {Excessive Urinary p75ecd is a Potential Indicator of Amyotrophic Lateral Sclerosis: An American Cohort Study.}, journal = {Current neuropharmacology}, volume = {}, number = {}, pages = {}, doi = {10.2174/011570159X352364250212035802}, pmid = {40353466}, issn = {1875-6190}, abstract = {INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is an idiopathic, fatal, and rapidly progressive neurodegenerative disease. At present, neurofilament light (NFL) and phosphorylated neurofilament heavy (pNfH) proteins in biological fluids are commonly known prognostic biomarkers, but their levels stabilize over time. Thus, there is a critical gap in the field to identify unique biomarkers that can aid disease diagnosis, progression and monitoring the therapy response.

AIM: To evaluate the presence of extracellular domain of p75 (p75ecd) in urine of ALS patients and healthy control volunteers in the North American cohort.

METHOD: An enzyme-linked immunoassay (ELISA) and creatinine assay was used to determine the levels of p75ecd and creatinine in the urine of ALS patients and healthy control volunteers respectively. This assay demonstrated clear discrimination in the levels of the p75ecd in the urine samples of ALS patients as compared to healthy individuals.

RESULTS: It was found that the concentration of p75ecd in ALS samples was significantly higher than that of healthy controls group. Additionally, high p75ecd levels were segregated with respect to age, sex, family history, occupation and drug treatment, medication status. Moreover, we observed differential expression patterns among the different stages of the disease. Our results followed the pattern that was observed in the Chinese, and Australian cohort.

CONCLUSION: Altogether, our results indicate that the development of an efficient system for the detection of elevated levels of p75ecd in the urine could serve as a useful modality for early ALS diagnosis, disease progression, and monitoring the effectiveness of therapeutic interventions.}, } @article {pmid40353188, year = {2025}, author = {Liu, Y and Topsakal, M and Zheng, K and Betancourt, LE and Woods, M and Roy, S and Patra, N and Leshchev, D and Halstenberg, P and Maltsev, DS and Dai, S and Ivanov, AS and Bryantsev, VS and Wishart, JF and Gakhar, R and Frenkel, AI and Gill, SK}, title = {Correlative analysis of Ni(ii) coordination states in molten salts using a combination of X-ray and optical spectroscopies and simulations.}, journal = {Chemical science}, volume = {16}, number = {23}, pages = {10414-10423}, pmid = {40353188}, issn = {2041-6520}, abstract = {Understanding the factors that control the speciation of metal ions in molten salts is crucial for the successful deployment of molten salts in both concentrated solar power and nuclear energy applications. The speciation of the Ni(ii) ion is of interest because it is a common corrosion product, and the distribution of coordination states it occupies is highly sensitive to the molten salt matrix. We employ in situ X-ray absorption spectroscopy (XAS), optical spectroscopy, and ab initio molecular dynamics (AIMD) simulations to investigate and understand the heterogeneities of Ni(ii) coordination in LiCl-KCl, NaCl-MgCl2, and LiCl-ZnCl2 molten salt systems. The main challenge lies in identifying the population distribution of Ni(ii) coordination states as a function of temperature and melt composition. We combined the multivariate curve resolution - alternating least squares (MCR-ALS) analysis of the XAS data and principal component analysis (PCA) of the optical spectra to determine the number of unique coordination states coexisting in the molten state, extract X-ray spectra for each state, and obtain their mixing fractions at different temperatures and for different salt mixtures. AIMD simulations were essential in identifying the coordination states corresponding to the deconvoluted spectra. The differences in the coordination states of Ni(ii) in different salt systems are discussed in terms of the effects of the varying polarizing powers of the cations in the host salt matrix on chloride ion coordination to Ni(ii). Such elucidation of the local structure adopted by metal ions enables a better understanding of the factors controlling the speciation of ions and their effect on molten salt properties.}, } @article {pmid40352904, year = {2025}, author = {Quizhpilema, JC and Legarda, A and Hidalgo, JM and Lecumberri, P and Jerico, I and Cabada, T}, title = {Asymmetric white matter degeneration in amyotrophic lateral sclerosis: a diffusion kurtosis imaging study of motor and extra-motor pathways.}, journal = {Frontiers in neuroscience}, volume = {19}, number = {}, pages = {1581719}, pmid = {40352904}, issn = {1662-4548}, abstract = {BACKGROUND: Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disease that lacks effective early biomarkers. This study investigated the potential of diffusion kurtosis imaging (DKI) as a non-invasive biomarker for detecting and monitoring ALS progression through a comprehensive analysis of white matter alterations.

METHODS: We performed a cross-sectional analysis of magnetic resonance images with advanced diffusion imaging techniques in ALS patients recruited from a neurodegenerative consultation service over a 3-year period and healthy controls. Our methodology employed multi-shell multi-tissue constrained spherical deconvolution (MSMT-CSD) for tract reconstruction and diffusion kurtosis imaging for microstructural analysis. The study focused particularly on the corticospinal tract and associated pathways, utilizing both tract-specific Bundle Analytics (BUAN) and whole-brain Tract-Based Spatial Statistics (TBSS) approaches.

RESULTS: The study included 33 ALS patients and 37 controls with no significant differences in age or gender. ALS patients predominantly presented with spinal onset and exhibited moderate functional impairment (ALSFRS-R: 39.09 ± 5). Whole-brain TBSS revealed widespread white matter alterations, with increased MD, RD, and AD, and decreased FA notably in the corona radiata, internal capsule, and corticospinal tracts. Detailed fiber tracking of the corticospinal tracts showed significant microstructural changes, with the left CST displaying pronounced increases in MD and AD alongside reduced FA, while the right CST exhibited distinctive regional variations. Additionally, analyses of the frontopontine and parietopontine tracts uncovered further alterations in diffusion metrics. Despite imaging findings, clinical-radiological correlations with functional scores and disease progression were not statistically significant.

CONCLUSIONS: This study explores DKI as a potential biomarker for ALS pathology, revealing microstructural changes in both motor and extra-motor pathways. Using whole-brain TBSS analysis and tractography with DIPY, we identified an asymmetric pattern of degeneration and involvement of integrative neural networks, providing new insights into ALS pathophysiology. These findings contribute to our understanding of the complex structural alterations in ALS and suggest that DKI-derived metrics may have utility in characterizing the disease process.}, } @article {pmid40351442, year = {2025}, author = {Khanal, P and Chikhale, R and Machhi, J}, title = {Editorial: Targeting neuroinflammation for novel therapeutics in neurodegenerative diseases.}, journal = {Frontiers in pharmacology}, volume = {16}, number = {}, pages = {1602495}, doi = {10.3389/fphar.2025.1602495}, pmid = {40351442}, issn = {1663-9812}, } @article {pmid40350993, year = {2025}, author = {Vedeler, A and Tartaglia, GG and Pastore, A}, title = {Annexin, a Protein for All Seasons: From Calcium Dependent Membrane Metabolism to RNA Recognition.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {47}, number = {7}, pages = {e70019}, pmid = {40350993}, issn = {1521-1878}, support = {ASTRA_855923//ERC / ; PNRRCN00000041andEPNRRCN3//Piano Nazionale di Ripresa e Resilienza of Italian MUR/ ; IVBM4PAP_101098989//EIC Pathfinder/ ; ARUK_PG2019B-020//ARUK / ; }, mesh = {*Annexins/metabolism/chemistry ; Humans ; *Calcium/metabolism ; Animals ; *Cell Membrane/metabolism ; *RNA/metabolism ; *RNA-Binding Proteins/metabolism ; Protein Binding ; }, abstract = {Annexins are a protein family well known to bind to phospholipids in a calcium-dependent way. They are involved in several different crucial cellular processes such as cell division, calcium signaling, membrane repair, vesicle trafficking, and apoptosis. Although RNA binding for some members of the family was reported long ago, it was only recently that it was shown that a common feature of the family is also the ability to bind RNA, a discovery that has added significantly to our perception of the cellular role of these proteins. In the present review, we discuss the properties of annexins under an updated light and the current knowledge on the RNA binding properties of annexins. We then focus specifically on annexin A11, because this is a less characterized member of the family but, at the same time, a potentially important component of the mRNA transport machinery in neurons. We hope to offer to the reader a more complete picture of the annexins' binding properties and new tools to evaluate the multifaceted functions of this important protein family.}, } @article {pmid40350723, year = {2025}, author = {Kuznetsova, DR and Kutlubaev, MA and Pervushina, EV}, title = {[Oculomotor disorders in patients with amyotrophic lateral sclerosis].}, journal = {Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova}, volume = {125}, number = {4}, pages = {7-12}, doi = {10.17116/jnevro20251250417}, pmid = {40350723}, issn = {1997-7298}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/complications/physiopathology ; *Ocular Motility Disorders/etiology/physiopathology/diagnosis ; Saccades ; Eye Movements ; }, abstract = {Oculomotor disorders are not typical manifestations of amyotrophic lateral sclerosis (ALS). Occasionally, this disease is associated with vertical gaze paresis, presenting a distinct type as «ALS+progressive supranuclear palsy». Studies using eye-tracking methods have revealed a variety of subclinical oculomotor disorders in this disease. These disorders can manifest as changes in reflex and voluntary saccades, antisaccades, smooth tracking eye movements, and fixations. A significant association between oculomotor disorders and clinical manifestations of ALS was reported. The occurrence of oculomotor disorders indicates the involvement of broader neuroanatomical structures, including the prefrontal cortex and basal ganglia. The lack of consistency in the data from different studies and their limited number emphasize the need for further research in this area.}, } @article {pmid40350633, year = {2025}, author = {Ishiura, H}, title = {[Genetics of Motor Neuron Diseases and Hereditary Spastic Paraplegia].}, journal = {Brain and nerve = Shinkei kenkyu no shinpo}, volume = {77}, number = {5}, pages = {481-491}, doi = {10.11477/mf.188160960770050481}, pmid = {40350633}, issn = {1881-6096}, mesh = {Humans ; *Spastic Paraplegia, Hereditary/genetics/diagnosis/therapy ; *Motor Neuron Disease/genetics/diagnosis ; }, abstract = {Motor neuron diseases encompass a range of phenotypes, including amyotrophic lateral sclerosis (ALS), primary lateral sclerosis (PLS), progressive muscular atrophy (PMA), and spinal muscular atrophy (SMA). Related conditions include spinal and bulbar muscular atrophy (SBMA) and hereditary motor and sensory neuropathy with proximal dominant involvement (HMSN-P). Hereditary spastic paraplegia (HSP)-a group of disorders primarily affecting the corticospinal tract-also exhibits diverse clinical manifestations. This review summarizes the genetic basis of these diseases, along with their clinical characteristics, diagnostic approaches, and disease-specific therapies.}, } @article {pmid40350531, year = {2025}, author = {Woo, TG and Han, J and Kim, Y and Hwang, YJ and Lee, M and Kang, SM and Park, S and Ji, Y and Chung, YH and Baek, S and Shin, E and Minju-Kim, and Jang, H and Shin, YJ and Kwon, Y and Kim, BH and Park, BJ}, title = {Inhibition of SOD1 trimerization is a novel drug target for ALS disease.}, journal = {Translational neurodegeneration}, volume = {14}, number = {1}, pages = {21}, pmid = {40350531}, issn = {2047-9158}, support = {RS-2024-00399681//Ministry of Science and ICT, South Korea/ ; RS-2024-00339289//Ministry of Science and ICT, South Korea/ ; RS-2023-00258714//Korea Drug Development Fund/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/drug therapy/metabolism/genetics ; *Superoxide Dismutase-1/metabolism/genetics/antagonists & inhibitors ; Animals ; Humans ; Mice ; Mice, Transgenic ; *Protein Multimerization/drug effects ; Disease Models, Animal ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that begins with motor neuron death in the spinal cord and cerebral cortex, ultimately resulting in death from respiratory distress (breathing failure). About 90% of ALS cases are sporadic, and 10% of ALS cases are of the inherited type with a genetic cause. About 150 different gene mutations have been reported so far. SOD1 is a well-identified gene associated with ALS. Indeed, SOD1 aggregation has been reported in ALS patients, but the mechanism of SOD1 aggregation remains unclear. Our previous work showed that inhibiting SOD1 aggregation with a hit compound (PRG-A-01) could reduce the SOD1-induced cytotoxicity and extend the lifespan of ALS mouse model (SOD1[G93A-Tg]). However, the low bioavailability and rapid degradation of the compound in vivo necessitates the development of a more effective candidate. We generated different derivatives and finally obtained the most potential drug candidate, PRG-A-04.

METHODS: Neuronal cell lines were transfected with the mutant SOD1 expression vector and incubated with PRG-A-04. SOD1 aggregation was examined by SOD1 oligomerization assay, immunofluorescence and dot blot assay. The interaction between GST-conjugated SOD1 recombinant proteins and PRG-A-04 was identified using LC-MS/MS and GST pull-down assay. To check the in vivo therapeutic effect of PRG-A-04, SOD1[G93A-Tg] mice were injected with PRG-A-04; then behavioral test, histological analysis and microarray were performed.

RESULTS: PRG-A-04 demonstrated favorable pharmacokinetics including high bioavailability and significant blood-brain barrier penetration. Indeed, oral administration of PRG-A-04 in ALS mouse model inhibited the aggregation of SOD1 in the spinal cord, protected against neuronal loss, and extended the lifespan of ALS mice by up to 3 weeks. In vitro, PRG-A-04 selectively bound to the mutant form of SOD1, but not the wild type, and efficiently inhibited the aggregation caused by SOD1-G147P (a SOD1 trimer stabilizer).

CONCLUSIONS: Our findings underscore the potential of targeting trimeric SOD1 in ALS treatment, positioning PRG-A-04 as a strong drug candidate for both familial and sporadic ALS.}, } @article {pmid40350485, year = {2025}, author = {Rofail, D and Chladek, M and Williams, B and Patel, N and Nowell, WB and Karantzoulis, S and Levy, O}, title = {Advancing Future Amyotrophic Lateral Sclerosis Medicines by Incorporating The Patient Voice Into Patient-Centered Holistic Measurement Strategies for Clinical and Real-World Studies: Results from Targeted Literature Reviews.}, journal = {Neurology and therapy}, volume = {14}, number = {4}, pages = {1311-1343}, pmid = {40350485}, issn = {2193-8253}, abstract = {INTRODUCTION: This analysis sought to understand the patient experience in amyotrophic lateral sclerosis (ALS) and to assess whether commonly used clinical outcome assessments (COAs) reliably and validly capture that experience.

METHODS: Two targeted literature reviews were conducted to identify and describe key concepts potentially important to patients (signs, symptoms, impacts), and identify commonly used COAs in ALS. Insights gained were used to map target COAs to concepts identified as potentially relevant to patients and their caregivers. COAs of interest were further examined to evaluate evidence of their validity and reliability within ALS.

RESULTS: Forty-three articles were identified for concept extraction. Signs and symptoms were identified across multiple themes: motor; non-motor; respiratory; cognitive; and behavioral. Patient impacts were identified across multiple themes: physical; functional; emotional; social; and other aspects of well-being. Caregiver impacts were identified across four themes: general; emotional; social; and physical. Of 236 unique COAs identified, 6 were found to provide the greatest coverage of potentially important concepts. Closer examination of these showed some evidence gaps supporting content validity and/or psychometric properties.

CONCLUSIONS: Several concepts related to ALS were identified that are relevant to patients in their daily lives. We identified and reviewed COAs commonly used in assessing these concepts, and found gaps in their content validity and/or psychometric properties. These findings suggest the need for further testing/refinement of existing tools, and the opportunity to use other instruments alongside those most frequently used (e.g., ALSFRS-R) to comprehensively capture the patient experience of ALS in future clinical trial and real-world studies.}, } @article {pmid40350140, year = {2025}, author = {Amin, MA and Zehravi, M and Sweilam, SH and Shatu, MM and Durgawale, TP and Qureshi, MS and Durgapal, S and Haque, MA and Vodeti, R and Panigrahy, UP and Ahmad, I and Khan, SL and Emran, TB}, title = {Neuroprotective potential of epigallocatechin gallate in Neurodegenerative Diseases: Insights into molecular mechanisms and clinical Relevance.}, journal = {Brain research}, volume = {1860}, number = {}, pages = {149693}, doi = {10.1016/j.brainres.2025.149693}, pmid = {40350140}, issn = {1872-6240}, mesh = {Humans ; *Catechin/analogs & derivatives/pharmacology/therapeutic use ; *Neuroprotective Agents/pharmacology/therapeutic use ; *Neurodegenerative Diseases/drug therapy/metabolism ; Animals ; Oxidative Stress/drug effects ; Clinical Relevance ; }, abstract = {Neurodegenerative diseases (NDs) such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis pose significant challenges due to their complex pathophysiology and lack of effective treatments. Green tea, rich in the epigallocatechin gallate (EGCG) polyphenolic component, has demonstrated potential as a neuroprotective agent with numerous medicinal applications. EGCG effectively reduces tau and Aβ aggregation in ND models, promotes autophagy, and targets key signaling pathways like Nrf2-ARE, NF-κB, and MAPK. This review explores the molecular processes that underlie EGCG's neuroprotective properties, including its ability to regulate mitochondrial dysfunction, oxidative stress, neuroinflammation, and protein misfolding. Clinical research indicates that EGCG may enhance cognitive and motor abilities, potentially inhibiting disease progression despite absorption and dose optimization limitations. The substance has been proven to slow the amyloidogenic process, prevent protein aggregation, decrease amyloid cytotoxicity, inhibit fibrillogenesis, and restructure fibrils for synergistic therapeutic effects. The review highlights the potential of EGCG as a natural, multi-targeted strategy for NDs but emphasizes the need for further clinical trials to enhance its therapeutic efficacy.}, } @article {pmid40349639, year = {2025}, author = {Maiocchi, A and Pedrini, M and Ferrari, V and Carreira, ASA and D'Amore, VM and Santoro, F and Di Porzio, A and Bosetti, M and Cristofani, R and Silvani, A and Brancaccio, D and Marinelli, L and Di Leva, FS and Provenzani, A and Poletti, A and Seneci, P}, title = {Design, synthesis and characterization of aryl bis-guanyl hydrazones as RNA binders of C9orf72 G4C2 extended repeats.}, journal = {European journal of medicinal chemistry}, volume = {293}, number = {}, pages = {117736}, doi = {10.1016/j.ejmech.2025.117736}, pmid = {40349639}, issn = {1768-3254}, mesh = {Humans ; *C9orf72 Protein/genetics/metabolism ; *Drug Design ; *Hydrazones/chemistry/pharmacology/chemical synthesis ; *RNA/metabolism/chemistry ; Structure-Activity Relationship ; G-Quadruplexes/drug effects ; Molecular Structure ; Dose-Response Relationship, Drug ; Amyotrophic Lateral Sclerosis/drug therapy/genetics ; }, abstract = {Expanded G4C2 repeats derived from mutations of the C9orf72 gene are causative factors in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) patients, leading to multiple pathological events. Bis thiophene para dinicotinimidamide 2a was reported to preferentially stabilize G-quadruplex G4C2 RNA structures at sub-micromolar concentrations. We replaced its amidine groups with BBB-compliant guanyl hydrazones, and carried out scaffold variations to improve water solubility. An eight-membered array was built around bis-thiophene- (4b-6a), bis-oxazole- (7b), diphenylurea diamide- (8b) and phenyldioxy ditriazolephenyl scaffolds (9a,b). Biological profiling of the array identified 4b as a promising, drug-like hit, active in cellular assays on ALS patient-derived cells.}, } @article {pmid40349338, year = {2025}, author = {Hölbling, BV and Gupta, Y and Marchi, PM and Atilano, ML and Flower, M and Ureña, E and Goulden, RA and Dobbs, HK and Katona, E and Mikheenko, A and Giblin, A and Awan, AR and Fisher-Ward, CL and O'Brien, N and Vaizoglu, D and Kempthorne, L and Wilson, KM and Gittings, LM and Carcolé, M and Ruepp, MD and Mizielinska, S and Partridge, L and Fratta, P and Tabrizi, SJ and Selvaraj, BT and Chandran, S and Armstrong, E and Whiting, P and Isaacs, AM}, title = {A multimodal screening platform for endogenous dipeptide repeat proteins in C9orf72 patient iPSC neurons.}, journal = {Cell reports}, volume = {44}, number = {5}, pages = {115695}, doi = {10.1016/j.celrep.2025.115695}, pmid = {40349338}, issn = {2211-1247}, mesh = {*C9orf72 Protein/genetics/metabolism ; Humans ; *Induced Pluripotent Stem Cells/metabolism ; *Neurons/metabolism ; *Dipeptides/metabolism/genetics ; Animals ; DNA Repeat Expansion ; Amyotrophic Lateral Sclerosis/genetics/metabolism ; Frontotemporal Dementia/genetics ; }, abstract = {Repeat expansions in C9orf72 are the most common cause of amyotrophic lateral sclerosis and frontotemporal dementia. Repeat-associated non-AUG (RAN) translation generates neurotoxic dipeptide repeat proteins (DPRs). To study endogenous DPRs, we inserted the minimal HiBiT luciferase reporter downstream of sense repeat derived DPRs polyGA or polyGP in C9orf72 patient iPSCs. We show these "DPReporter" lines sensitively and rapidly report DPR levels in lysed and live cells and optimize screening in iPSC neurons. Small-molecule screening showed the ERK1/2 activator periplocin dose dependently increases DPR levels. Consistent with this, ERK1/2 inhibition reduced DPR levels and prolonged survival in C9orf72 repeat expansion flies. CRISPR knockout screening of all human helicases revealed telomere-associated helicases modulate DPR expression, suggesting common regulation of telomeric and C9orf72 repeats. These DPReporter lines allow investigation of DPRs in their endogenous context and provide a template for studying endogenous RAN-translated proteins, at scale, in other repeat expansion disorders.}, } @article {pmid40349108, year = {2025}, author = {Weiss, A and Gilbert, JW and Rivera Flores, IV and Belgrad, J and Ferguson, C and Dogan, EO and Wightman, N and Mocarski, K and Echeverria, D and Harkins, AL and Summers, A and Bramato, B and McHugh, N and Furgal, R and Yamada, N and Cooper, D and Monopoli, K and Godinho, BMDC and Hassler, MR and Yamada, K and Greer, P and Henninger, N and Brown, RH and Khvorova, A}, title = {RNAi-mediated silencing of SOD1 profoundly extends survival and functional outcomes in ALS mice.}, journal = {Molecular therapy : the journal of the American Society of Gene Therapy}, volume = {33}, number = {8}, pages = {3917-3938}, doi = {10.1016/j.ymthe.2025.05.010}, pmid = {40349108}, issn = {1525-0024}, mesh = {Animals ; *Amyotrophic Lateral Sclerosis/genetics/therapy/mortality/pathology/metabolism ; *Superoxide Dismutase-1/genetics/antagonists & inhibitors ; Mice ; Disease Models, Animal ; *RNA Interference ; Mice, Transgenic ; Humans ; *RNA, Small Interfering/genetics/administration & dosage ; Gene Silencing ; Motor Neurons/metabolism/pathology ; Superoxide Dismutase/genetics ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative condition, with 20% of familial and 2%-3% of sporadic cases linked to mutations in the cytosolic superoxide dismutase (SOD1) gene. Mutant SOD1 protein is toxic to motor neurons, making SOD1 gene suppression a promising approach, supported by preclinical data and the 2023 Federal Drug Administration (FDA) approval of the GapmeR ASO targeting SOD1, tofersen. Despite the approval of an ASO and the optimism it brings to the field, the pharmacodynamics and pharmacokinetics of therapeutic SOD1 modulation can be improved. Here, we developed a chemically stabilized divalent siRNA scaffold (di-siRNA) that effectively suppresses SOD1 expression in vitro and in vivo. With optimized chemical modification, it achieves remarkable CNS tissue permeation and SOD1 silencing in vivo. Administered intraventricularly, di-siRNA[SOD1] extended survival in SOD1-G93A ALS mice, increasing survival beyond that previously seen in these mice by ASO modalities, slowed disease progression according to the standard ALS preclinical endpoints, and attenuated ALS neuropathology. These properties offer an improved therapeutic strategy for SOD1-mediated ALS and may extend to other dominantly inherited neurological disorders.}, } @article {pmid40348172, year = {2025}, author = {Xin, Z and Xin, C and Huo, J and Liu, Q and Dong, H and Li, X and Liu, Y and Li, R}, title = {Stage-dependent efficacy of short-chain fatty acids in amyotrophic lateral sclerosis: Insights into autophagy and neuroprotection.}, journal = {Life sciences}, volume = {374}, number = {}, pages = {123686}, doi = {10.1016/j.lfs.2025.123686}, pmid = {40348172}, issn = {1879-0631}, mesh = {*Amyotrophic Lateral Sclerosis/drug therapy/pathology/metabolism ; Animals ; *Autophagy/drug effects ; Mice ; *Fatty Acids, Volatile/pharmacology/metabolism ; Disease Models, Animal ; Mice, Transgenic ; Superoxide Dismutase-1/metabolism/genetics ; Spinal Cord/metabolism/pathology/drug effects ; Humans ; *Neuroprotection/drug effects ; Male ; *Neuroprotective Agents/pharmacology ; Propionates/pharmacology ; Butyrates/pharmacology ; Mice, Inbred C57BL ; }, abstract = {AIMS: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with limited therapeutic options. Previously, we have shown that a combination of multiple probiotic strains can regulate intestinal flora, increase serum short-chain fatty acids (SCFAs), reduce abnormal protein accumulation in the spinal cord, and protect neurons. It is necessary to explore the mechanism to provide therapeutic targets for ALS.

MATERIALS AND METHODS: This study utilizes live cell imaging, mouse behavioral research, immunofluorescence, Electron microscopy, Western Blot, and polymerase chain reaction to explore the impact of various SCFAs on ALS animal and cell models, as well as their underlying mechanisms.

KEY FINDINGS: We found SCFAs, including butyrate and propionate can increase the levels of acetylated histones, enhance the expression of autophagy-related genes and regulate autophagy, leading to a decrease in abnormal SOD1 aggregation, reduction of cell damage, and enhancement of cell proliferation in NSC34-SOD1[G93A] cells. Furthermore, systemic administration of butyrate and propionate can regulate autophagy, reduce SOD1 aggregation, and protect spinal cord neurons in SOD1[G93A] mice. However, these favorable effects of butyrate and propionate are greatly decreased at later stages of the disease process in SOD1[G93A] mice.

SIGNIFICANCE: Our study revealed that the positive impact of SCFAs in autophagy could be a promising focus for ALS therapy. However, this effect might have different impacts in different stages of ALS.}, } @article {pmid40348049, year = {2025}, author = {Reda, A and Khalil, H and Bahgat, EA and Fawzy, MG}, title = {Univariate versus multivariate approaches for resolving the overlapped spectra of azelastine hydrochloride and mometasone furoate.}, journal = {Analytical biochemistry}, volume = {704}, number = {}, pages = {115902}, doi = {10.1016/j.ab.2025.115902}, pmid = {40348049}, issn = {1096-0309}, mesh = {*Mometasone Furoate/analysis/chemistry ; *Phthalazines/analysis/chemistry ; Multivariate Analysis ; Principal Component Analysis ; Least-Squares Analysis ; }, abstract = {Azelastine hydrochloride (AZE) and Mometasone furoate (MOM) combination is used to treat allergic rhinitis' symptoms. The aim of this work is to qualitatively and quantitatively analyze both medications using univariate and multivariate spectrophotometric techniques in a comparative study. Regarding univariate approaches; AZE was quantified by direct measurement at 291 nm within (5-60 μg/mL) concentration range. While, MOM was assayed by absorption correction (AC) approach at 250 nm within the range of (2-18 μg/mL). The LOD values for AZE and MOM were (0.79 μg/mL) and (0.21 μg/mL), respectively. Classical least squares (CLS), partial least squares (PLS), principal component regression (PCR), multivariate curve resolution-alternating least squares (MCR-ALS) and artificial neural networks (ANN) were the applied multivariate chemometric models. The proposed methods were utilized for analyzing the binary mixture in laboratory-synthetic mixtures and pharmaceutical preparation with correlation coefficients values ≥ 0.9996. No statistically significant variation was found between the applied methods and the reported HPLC one. The methods' sustainability was assessed using blue applicability grade index (BAGI) and Red-Green-Blue 12 (RGB12) metrics. The obtained findings revealed that the suggested methodologies are safer option than the published HPLC technique for the conventional pharmaceutical analysis of the studied medications.}, } @article {pmid40347946, year = {2025}, author = {Blazev, R and Zee, BM and Peckham, H and Ng, YK and Lewis, CTA and Zhang, C and McNamara, JW and Goodman, CA and Gregorevic, P and Ochala, J and Steyn, FJ and Ngo, ST and Stokes, MP and Parker, BL}, title = {Site-specific quantification of the in vivo UFMylome reveals myosin modification in ALS.}, journal = {Cell reports methods}, volume = {5}, number = {5}, pages = {101048}, pmid = {40347946}, issn = {2667-2375}, mesh = {*Amyotrophic Lateral Sclerosis/metabolism/pathology ; Humans ; Animals ; Mice ; *Myosins/metabolism ; Muscle, Skeletal/metabolism/pathology ; Ubiquitination ; Protein Processing, Post-Translational ; *Ubiquitins/metabolism ; Mass Spectrometry ; }, abstract = {UFMylation is a ubiquitin-like protein modification of Ubiquitin Fold Modifier 1 (UFM1) applied to substrate proteins and regulates several cellular processes such as protein quality control. Here, we describe the development of an antibody-based enrichment approach to immunoprecipitate remnant UFMylated peptides and identification by mass spectrometry. We used this approach to identify >200 UFMylation sites from various mouse tissues, revealing extensive modification in skeletal muscle. In vivo knockdown of the E2 ligase, UFC1, followed by enrichment and analysis of remnant UFMylated peptides quantified concomitant down-regulation and validation of a subset of modification sites, particularly myosin UFMylation. Furthermore, we show that UFMylation is increased in skeletal muscle biopsies from people living with amyotrophic lateral sclerosis (plwALS). Quantification of UFMylation sites in these biopsies with multiplexed isotopic labeling reveal prominent increases in myosin UFMylation. Our data suggest that in vivo UFMylation is more complex than previously thought.}, } @article {pmid40347374, year = {2025}, author = {Varshney, V and Gabble, BC and Bishoyi, AK and Varma, P and Qahtan, SA and Kashyap, A and Panigrahi, R and Nathiya, D and Chauhan, AS}, title = {Exploring Exosome-Based Approaches for Early Diagnosis and Treatment of Neurodegenerative Diseases.}, journal = {Molecular neurobiology}, volume = {}, number = {}, pages = {}, pmid = {40347374}, issn = {1559-1182}, abstract = {Neurodegenerative diseases (NDs), like Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and Amyotrophic Lateral Sclerosis (ALS), present an increasingly significant global health burden, primarily due to the lack of effective early diagnostic tools and treatments. Exosomes-nano-sized extracellular vesicles secreted by nearly all cell types-have emerged as promising candidates for both biomarkers and therapeutic agents in NDs. This review examines the biogenesis, molecular composition, and diverse functions of exosomes in NDs. Exosomes play a crucial role in mediating intercellular communication. They are capable of reflecting the biochemical state of their parent cells and have the ability to cross the blood-brain barrier (BBB). In doing so, they facilitate the propagation of pathological proteins, such as amyloid-beta (Aβ), tau, and alpha-synuclein (α-syn), while also enabling the targeted delivery of neuroprotective compounds. Recent advancements in exosome isolation and engineering have opened up new possibilities for diagnostic and therapeutic strategies. These range from the discovery of non-invasive biomarkers to innovative approaches in gene therapy and drug delivery systems. However, challenges related to standardization, safety, and long-term effects must be addressed before exosomes can be translated into clinical applications. This review highlights both the promising potential and the obstacles that must be overcome to leverage exosomes in the treatment of NDs and the transformation of personalized medicine.}, } @article {pmid40346952, year = {2025}, author = {Çelik, F}, title = {Xenon in ALS Treatment: What Are We Waiting for?.}, journal = {CNS neuroscience & therapeutics}, volume = {31}, number = {5}, pages = {e70435}, pmid = {40346952}, issn = {1755-5949}, } @article {pmid40346939, year = {2025}, author = {Santibanez, RCG and Fournier, CN}, title = {The Necessity of Overcoming Racial Disparities in Amyotrophic Lateral Sclerosis Care and Research.}, journal = {Muscle & nerve}, volume = {72}, number = {1}, pages = {5-6}, doi = {10.1002/mus.28433}, pmid = {40346939}, issn = {1097-4598}, } @article {pmid40346885, year = {2025}, author = {Tahedl, M and Kleinerova, J and Doherty, MA and Hengeveld, JC and McLaughlin, RL and Hardiman, O and Tan, EL and Bede, P}, title = {Progressive Thalamo-Cortical Disconnection in Amyotrophic Lateral Sclerosis Genotypes: Structural Degeneration and Network Dysfunction of Thalamus-Relayed Circuits.}, journal = {European journal of neurology}, volume = {32}, number = {5}, pages = {e70146}, pmid = {40346885}, issn = {1468-1331}, support = {17/CDA/4737/SFI_/Science Foundation Ireland/Ireland ; SFI SP20/SP/8953/SFI_/Science Foundation Ireland/Ireland ; HRB EIA-2017-019 & JPND-Cofund-2-2019-1/HRBI_/Health Research Board/Ireland ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/pathology/diagnostic imaging/physiopathology ; *Thalamus/pathology/diagnostic imaging/physiopathology ; Male ; Female ; Middle Aged ; Aged ; C9orf72 Protein/genetics ; Neural Pathways/pathology/diagnostic imaging/physiopathology ; Magnetic Resonance Imaging ; *Cerebral Cortex/pathology/diagnostic imaging/physiopathology ; Genotype ; Adult ; Prospective Studies ; *Nerve Net/pathology/diagnostic imaging/physiopathology ; Longitudinal Studies ; }, abstract = {BACKGROUND: The thalamus is a key subcortical hub of numerous corticobasal and corticocortical circuits mediating a wealth of cognitive, behavioural, sensory and motor processes. While thalamic pathology is increasingly recognised in amyotrophic lateral sclerosis, its degeneration is often assessed in isolation instead of adopting a network-wise perspective and assessing the integrity of its rich cortical projections.

METHODS: A prospective imaging study was conducted in a cohort of genetically stratified patients to assess the structural and functional integrity of thalamo-cortical circuits and volumetric alterations longitudinally.

RESULTS: The white matter integrity of thalamic projections to the anterior cingulate cortex, cerebellum, dorsolateral prefrontal cortex (DLPFC), Heschl's gyrus, medial frontal gyrus (MFG), orbitofrontal cortex, parietal cortex, postcentral gyrus and precentral gyrus (PreCG) is affected at baseline in ALS, which is more marked in C9orf72 hexanucleotide repeat carriers. Precentral gyrus and cerebellar grey matter volumes are also reduced, particularly in C9orf72. Longitudinal analyses capture progressive disconnection between the thalamus and frontal regions (DLPFC and MFG) in both C9orf72 positive and sporadic patients and progressive thalamo-PreCG disconnection in the sporadic C9orf72 negative cohort. Functional connectivity analyses revealed increasing thalamo-cerebellar connectivity in sporadic ALS and increasing thalamo-DLPFC connectivity in intermediate-length CAG repeat expansion carriers in ATXN2 over time.

DISCUSSION: Our data provide evidence of extensive thalamo-cortical connectivity alterations in ALS. Corticobasal circuits mediating extrapyramidal, somatosensory, cognitive and behavioural functions are increasingly affected as the disease progresses. The degeneration of thalamic projections support the conceptualisation of ALS as a 'network disease' and the notion of 'what wires together degenerates together'.}, } @article {pmid40346540, year = {2025}, author = {Lombardi, I and Ferrero, C and Vulcano, E and Rasà, DM and Gelati, M and Pastor, D and Carletti, RM and de la Morena, S and Profico, DC and Longobardi, S and Lazzarino, E and Perciballi, E and Rosati, JD and Martinez, S and Vercelli, A and Vescovi, AL and Boido, M and Ferrari, D}, title = {Safety and efficacy evaluation of intracerebroventricular human neural stem cell transplantation in SOD1 mice as a novel approach for ALS.}, journal = {Journal of translational medicine}, volume = {23}, number = {1}, pages = {529}, pmid = {40346540}, issn = {1479-5876}, support = {Fondazione Revert Onlus//Fondazione Revert Onlus/ ; 2019-ATESP-0028//Università degli Studi di Milano-Bicocca/ ; Dipartimenti di Eccellenza 2023-2027 to Department of Neuroscience "Rita Levi Montalcini"//Ministero dell'Istruzione, dell'Università e della Ricerca/ ; R24-5x1000 to Fondazione IRCCS Casa Sollievo della Sofferenza//Ministero della Salute/ ; }, mesh = {Animals ; *Amyotrophic Lateral Sclerosis/therapy/pathology/physiopathology ; *Neural Stem Cells/transplantation/cytology ; Humans ; *Superoxide Dismutase-1/metabolism ; Mice ; Disease Models, Animal ; Mice, Transgenic ; Injections, Intraventricular ; *Stem Cell Transplantation ; Treatment Outcome ; Spinal Cord/pathology ; }, abstract = {BACKGROUND: Neural stem cell (NSC) transplantation holds promising therapeutic potential for neurodegenerative disorders like amyotrophic lateral sclerosis (ALS). However, pre-clinical studies and early-phase clinical trials have faced challenges hindering the effective clinical translation of this approach. Crucial hurdles include the side-effects of prolonged immunosuppression, concerns regarding cell origin and transplantation dosage, identification of the most appropriate therapeutic window, and invasiveness of surgical procedures. Here, we assessed the safety and efficacy of intracerebroventricular (ICV) hNSC transplantation as a novel and possibly more effective experimental approach for ALS.

METHODS: We evaluated the safety of administering up to 1 × 10[6] hNSCs in immunodeficient mice and assessed their potential efficacy in reducing ALS hallmarks employing the SOD1[G93A] mouse model. Both transient (15 days) and prolonged immunosuppression regimens, at low (15 mg/kg) and high (30 mg/kg) doses, were tested along with two different cell dosages (3 × 10[5] and 1 × 10[6]).

RESULTS: Our study suggests that: (i) a bilateral ICV transplantation of 1 × 10[6] hNSCs is safe and non-tumorigenic in immunodeficient hosts; (ii) sustained and high-dose immunosuppression is essential for ensuring cell survival in immunocompetent SOD1[G93A] mice; and (iii) hNSCs may delay motor symptom progression and reduce spinal cord microgliosis in SOD1[G93A] mice when administered in the lateral ventricles under prolonged high-dose (30 mg/kg) immunosuppression.

CONCLUSIONS: ICV transplantation of hNSCs emerges as a safe and promising strategy for ALS, demonstrating potential to delay motor decline and reduce spinal cord microgliosis. However, sustained high-dose immunosuppression is crucial for therapeutic efficacy, emphasizing the need for further optimization to overcome translational challenges and achieve durable clinical benefits.}, } @article {pmid40346135, year = {2025}, author = {Abril, SP and Rincón-Díaz, N and Puyana, M and Castellanos, L and Ramos, FA}, title = {Photoprotective activity from Colombian Caribbean brown algae using HPLC-DAD metabolic profiling by MCR-ALS data analysis.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {16204}, pmid = {40346135}, issn = {2045-2322}, support = {1101-852-69964//Ministerio de Ciencia, Tecnología e Innovación/ ; 1101-852-69964//Ministerio de Ciencia, Tecnología e Innovación/ ; 1101-852-69964//Ministerio de Ciencia, Tecnología e Innovación/ ; 1101-852-69964//Ministerio de Ciencia, Tecnología e Innovación/ ; 1101-852-69964//Ministerio de Ciencia, Tecnología e Innovación/ ; }, mesh = {Chromatography, High Pressure Liquid/methods ; *Phaeophyceae/metabolism/chemistry ; Antioxidants/pharmacology/chemistry ; *Metabolomics/methods ; Ultraviolet Rays/adverse effects ; Caribbean Region ; *Sunscreening Agents/pharmacology/chemistry ; *Metabolome ; }, abstract = {Although synthetic UV filters are widely used for skin photoprotection, growing concerns about their environmental and health impacts underscore the need for new, effective photoprotective products. This study aimed to develop a screening methodology for selecting brown macroalgae extracts with potential photoprotective activity. The approach integrates in vitro photoprotection assays, antioxidant TLC-DPPH assays, and HPLC-DAD metabolic profiling of 17 algal samples from the Dictyota, Canistrocarpus, Stypopodium, Sargassum, Lobophora, Padina, and Turbinaria genera. The results revealed concentration-dependent sun protection factor (SPF) values ranging from 0.403 to 2.915, UVA ratios (UVAr) ranging from 0.167 to 3.623, critical wavelengths (λc) ranging from 335 to 393 nm, and antioxidant DPPH-TLC activity in 10 of the evaluated extracts. These findings were correlated with the HPLC-DAD metabolic profile using the Multivariate Curve Resolution- Alternating Least Squares (MCR-ALS) algorithm and multivariate data analysis tools. Extracts from Canistrocarpus cervicornis (CCe) and Stypopodium zonale (SS) presented the most promising photoprotective activity. Through NMR and MS analysis, 2,5,7-trihydroxy-2-pentadecylchroman-4-one (1), fucoxanthin, pheophytin a, and pheophorbide a were identified as the main contributors to this activity. This methodology was successfully implemented and could be further used to screen for photoprotective activity in algal species.}, } @article {pmid40345258, year = {2025}, author = {Sepulveda, M and Martínez Traub, F and Ojeda, P and Perez, V and Ojeda, J and Mella, J and Diaz, R and Rozas, P and Mansilla-Jaramillo, M and Zuleta, A and Diaz, G and Kerr, B and Woehlbier, U and Henríquez, JP and Medinas, DB and Hetz, C}, title = {Expression of protein disulfide isomerase A3Q481K variant associated with amyotrophic lateral sclerosis triggers disease features in mice.}, journal = {Neurobiology of disease}, volume = {212}, number = {}, pages = {106947}, doi = {10.1016/j.nbd.2025.106947}, pmid = {40345258}, issn = {1095-953X}, mesh = {Animals ; *Amyotrophic Lateral Sclerosis/genetics/pathology/metabolism ; *Protein Disulfide-Isomerases/genetics/metabolism ; Mice, Transgenic ; Mice ; Motor Neurons/pathology/metabolism ; Endoplasmic Reticulum Stress/genetics ; Spinal Cord/pathology/metabolism ; Humans ; Neuromuscular Junction/pathology ; Disease Models, Animal ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by loss of motoneurons and compromised proteostasis. Dysfunction of the endoplasmic reticulum (ER) has been identified as a transversal pathogenic mechanism associated with motoneurons vulnerability in ALS. Protein disulfide isomerases (PDIs) are key enzymes catalyzing protein folding at the ER that are altered in the disease, involving biochemical and genetic perturbations. In ALS cases, we previously identified variants in the gene encoding PDIA3 (also known as Grp58 or ERp57), which were associated with altered neurite outgrowth in cell culture and abnormal motoneuron connectivity in zebrafish. Here, we report the generation of transgenic mice expressing the ALS-associated PDIA3[Q481K] variant. Moderate PDIA3[Q481K] overexpression resulted in altered motor capacity accompanied by decreased motoneuron number. The adverse effects of PDIA3[Q481K] expression were associated with induction of ER stress in the spinal cord and subtle morphological changes in neuromuscular junctions. Our results suggest that the PDIA3[Q481K] variant is likely pathogenic and its overexpression in mice recapitulate some ALS features, further supporting the concept that altered proteostasis due to PDI dysfunction may predispose an individual to develop the disease.}, } @article {pmid40345169, year = {2025}, author = {Meng, Y and Li, W and Zhang, Y and Li, Y and He, Y and Zhang, N}, title = {ANXA11 Mutations in the FTD Spectrum: A Novel Finding in a Patient With Semantic Variant Primary Progressive Aphasia.}, journal = {European journal of neurology}, volume = {32}, number = {5}, pages = {e70187}, pmid = {40345169}, issn = {1468-1331}, support = {24JCYBJC00650//Natural Science Foundation of Tianjin Municipality/ ; 2022ZD0211605//Science and Technology Innovation 2030 Major Projects/ ; }, mesh = {Aged ; Humans ; *Annexins/genetics ; *Aphasia, Primary Progressive/genetics ; *Frontotemporal Dementia/genetics ; *Mutation/genetics ; }, abstract = {BACKGROUND: Semantic variant primary progressive aphasia (svPPA) is typically a sporadic disorder, and few cases have been linked to ANXA11 mutations. Comprehensive analyses of genetic mutations in svPPA are limited. Furthermore, the clinical and genetic distinctions between typical svPPA and right temporal variant frontotemporal dementia (rtvFTD) are poorly understood.

METHODS: A 68-year-old patient with svPPA carrying a heterozygous ANXA11 c.119A>G (p.D40G) mutation underwent comprehensive neuropsychological, neuroimaging, and genetic assessments at baseline and at the one-year follow-up timepoint. Additionally, systematic reviews were conducted to identify reported cases of ANXA11 mutations in the FTD spectrum and the genetic mutations associated with svPPA. Clinical-genetic profiles of typical svPPA and rtvFTD were compared based on data from the literature.

RESULTS: Thirty-two patients with ANXA11 mutations were identified, including 11 with pure FTD phenotypes and the majority exhibiting FTD-amyotrophic lateral sclerosis (ALS). Among 167 svPPA-related cases, MAPT, GRN, and C9ORF72 mutations were most frequently implicated; ANXA11 mutations were primarily identified in East Asian patients. Comparative analysis revealed overlapping age at onset, disease duration, sex distribution, and APOE ε4 allele frequencies between typical svPPA and rtvFTD but differing clinical presentations.

CONCLUSIONS: This study reports a case of typical svPPA in China associated with the ANXA11 p.D40G mutation without ALS-related features. Our findings highlight the importance of ANXA11 mutations in FTD pathogenesis.}, } @article {pmid40345155, year = {2025}, author = {Liu, X and Liu, X and Zhan, J and Yuan, W and Zhu, Y and Huang, W and Li, H and Liu, T and Amine, K and Li, H and Yu, G}, title = {High-Performance Al-S Batteries by Spin Polarization Modulation via Catalytic Ni-MoS2 Nanosheets.}, journal = {Angewandte Chemie (International ed. in English)}, volume = {64}, number = {29}, pages = {e202503835}, doi = {10.1002/anie.202503835}, pmid = {40345155}, issn = {1521-3773}, support = {51804173//National Natural Science Foundation of China/ ; F-1861//Welch Foundation/ ; }, abstract = {Aluminum-sulfur (Al-S) batteries catalysts with adsorption and catalytic capabilities can effectively improve the slow redox kinetics, but the current research often ignores the effect of optimizing the electronic structure of the catalyst on improving charge transfer and adsorption. Here, Ni-doped monolayer MoS2 nanosheets are synthesized and used as a catalytic additive for the sulfur cathode. The addition of Ni promotes spin splitting of 4d orbital of Mo, thereby affecting polarization degree of the basal plane sulfur and making it change from a low spin state to a high spin one. This high spin configuration raises the electron energy level and provides an active electron state to react with aluminum polysulfides (AlPSs), which optimizes the adsorption energy. At the same time, it accelerates electron transfer and lowers the energy barrier for the overall conversion of the polysulfides. Benefiting from these features, Al-S batteries based on rationally designed S@Ni-MoS2/C cathodes exhibit a high initial capacity (1603.0 mAh g[-1] at 0.5 A g[-1]) and extraordinary cycling stability (0.035% capacity decay rate during 2000 cycles). This study showcases a spin-polarized electronic structure control strategy to enhance catalytic activity, providing a viable approach for developing efficient catalysts for practical Al-S batteries.}, } @article {pmid40344943, year = {2025}, author = {Zhou, ZD and Yi, L and Popławska-Domaszewicz, K and Chaudhuri, KR and Jankovic, J and Tan, EK}, title = {Glucagon-like peptide-1 receptor agonists in neurodegenerative diseases: Promises and challenges.}, journal = {Pharmacological research}, volume = {216}, number = {}, pages = {107770}, doi = {10.1016/j.phrs.2025.107770}, pmid = {40344943}, issn = {1096-1186}, mesh = {Humans ; *Glucagon-Like Peptide-1 Receptor Agonists ; Animals ; *Neurodegenerative Diseases/drug therapy/metabolism ; *Neuroprotective Agents/therapeutic use ; *Hypoglycemic Agents/therapeutic use ; Glucagon-Like Peptide-1 Receptor/metabolism ; }, abstract = {Glucagon-like peptide-1 (GLP-1) receptor agonists (GRA) belong to a class of compounds that reduce blood glucose and energy intake by simulating actions of endogenous incretin hormone GLP-1 after it is released by the gut following food consumption. They are used to treat type 2 diabetes mellitus (T2DM) and obesity and have systemic effects on various organs, including the brain, liver, pancreas, heart, and the gut. Patients with T2DM have a higher risk of developing neurodegenerative diseases (NDs), including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and Huntington's disease (HD), accompanied by more severe motor deficits and faster disease progression, suggesting dysregulation of insulin signaling in these diseases. Experimental studies have shown that GRA have protective effects to modulate neuroinflammation, oxidative stress, mitochondrial and autophagic functions, and protein misfolding. Hence the compounds have generated enormous interest as novel therapeutic agents against NDs. To date, clinical trials have shown that three GRA, exenatide, liraglutide and lixisenatide can improve motor deficits as an add-on therapy in PD patients and liraglutide can improve cognitive function in AD patients. The neuroprotective effects of these and other GRA, such as PT320 (a sustained-released exenatide) and semaglutide, are still under investigation. The dual GLP-1/gastric inhibitory polypeptide (GIP) receptor agonists have been demonstrated to have beneficial effects in AD and PD mice models. Overall, GRA are highly promising novel drugs, but future clinical studies should identify which subsets of patients should be targeted as potential candidates for their symptomatic and/or neuroprotective benefits, investigate whether combinations with other classes of drugs can further augment their efficacy, and evaluate their long-term disease-modifying and adverse effects.}, } @article {pmid40344633, year = {2025}, author = {Tang, S and Shi, J and Li, X and Yang, M and Li, C and Zhang, D and Yang, S and Mei, C and Luo, Z and Zhang, L and Zhang, W and Zhang, C and Zhu, C and Ma, X and Xia, R and Chen, Y and Zhang, J and Chen, Q and Chen, S and Xie, Q and Yu, F}, title = {Development and Breeding of Herbicide-Resistant Sorghum for Effective Cereal-Legume Intercropping.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {12}, number = {27}, pages = {e2503083}, pmid = {40344633}, issn = {2198-3844}, support = {YZGG-04//Sorghum Seed Industry Innovation and Improved Joint Research Project of Shanxi Province/ ; 2023YFD1200700//National Key R&D Program of China/ ; 2023YFF1001400//National Key R&D Program of China/ ; 32222010//National Natural Science Foundation of China/ ; 32430077//National Natural Science Foundation of China/ ; }, abstract = {Weeds bring a serious challenge to crop production, and herbicides is the most effective and economic way to manage it in field. Sorghum is a critical crop for staple food, fodder, and biofuel. However, the lack of herbicide-resistant sorghum germplasm severely impedes its production. Here, we conducted a large-scale screening and identified 13 sorghum mutant lines resistant to imidazolinone (IMI) herbicides. Two unique mutation sites in SbALS (acetolactate synthase), thus namely Sbals-1 (A93T) and Sbals-2 (S624N) are discovered, both enhance sorghum tolerance to imazamox. Notably, under high concentrations of imazamox, sbals-1 presented a superior growth phenotype and elevated SbALS activity than sbals-2, a difference that can be attributed to the predicted protein structures. Breeding with Sbals, both grain- and grass-type sorghum, shows great weed control and field performance. The herbicide imazamox resistance is further evaluated in a soybean population for sorghum-soybean strip intercropping, identifying 123 highly resistant soybean varieties. Field intercropping tests indicated health growth of both soybean and sorghum lines post-imazamox treatment, which enhance field clearance of weed. This study, therefore, provides valuable insights not only for herbicide-resistant sorghum breeding but also for the successful implementation of efficient and sustainable cereal-legume intercropping systems.}, } @article {pmid40344624, year = {2025}, author = {Temme, N and Haehre, T and Boyher, C and Hoppe, L and Davenport, C and Stumo, Z and Prenzler, K and Maeser, A and Pflugmacher, M and Koch, K and Stahl, DJ}, title = {Host-induced gene silencing of the amino acid biosynthesis gene acetolactate synthase of Phytophthora infestans caused strong enhanced late blight resistance of potato in the field.}, journal = {Plant biotechnology journal}, volume = {23}, number = {8}, pages = {3054-3067}, pmid = {40344624}, issn = {1467-7652}, support = {Forschungsvorhaben 0315701C//Bundesministerium für Bildung und Forschung/ ; GABI-PLANT-KBBE II//Bundesministerium für Bildung und Forschung/ ; }, mesh = {*Phytophthora infestans/genetics/enzymology ; *Solanum tuberosum/microbiology/genetics/immunology ; *Acetolactate Synthase/genetics/metabolism ; *Plant Diseases/microbiology/genetics/immunology ; *Disease Resistance/genetics ; *Gene Silencing ; *Amino Acids/biosynthesis ; }, abstract = {Late blight caused by Phytophthora infestans is the most serious disease of potatoes. Here we present the effectiveness of the host-induced gene silencing (HIGS) technology against an amino acid biosynthesis gene of the pathogen to increase the resistance against the plant-infecting oomycete in the field. A RNAi hairpin construct directed against the acetolactate synthase (ALS) gene of Phytophthora infestans was transferred into potato. HIGS-ALS potato lines displayed efficient target gene silencing revealed by a luciferase reporter gene assay. Plant-derived siRNAs targeting the oomycete's ALS gene were detected by small RNA sequencing. ALS gene expression of P. infestans was reduced during the early infection stages of HIGS-ALS potatoes, as shown by qRT-PCR. HIGS-ALS plants revealed an enhanced late blight resistance in detached leaf assays. ALS gene silencing also conferred strong enhanced late blight resistance to the HIGS lines in trials under near-field conditions in Europe and in field trials in the USA against European and US P. infestans isolates, respectively. These results demonstrated the value of the HIGS technology for the development of a new quantitative resistance source for potato against Phytophthora infestans.}, } @article {pmid40342184, year = {2025}, author = {Ribeiro, VHV and Gallagher, J and Mallory-Smith, C and Barroso, J and Brunharo, CACG}, title = {Multiple Origins or Widespread Gene Flow in Agricultural Fields? Regional Population Genomics of Herbicide Resistance in Bromus tectorum.}, journal = {Molecular ecology}, volume = {34}, number = {11}, pages = {e17791}, pmid = {40342184}, issn = {1365-294X}, support = {//Oregon Wheat Commission/ ; //College of Agricultural Sciences, Pennsylvania State University/ ; Project#PEN04859,Accession#7005632//USDA National Institute of Food and Agriculture/ ; }, mesh = {*Herbicide Resistance/genetics ; *Gene Flow ; Acetolactate Synthase/genetics/antagonists & inhibitors ; Herbicides/pharmacology ; *Bromus/genetics/drug effects ; *Genetics, Population ; Mutation ; Genetic Variation ; Agriculture ; }, abstract = {The repeated evolution of herbicide resistance in agriculture provides an unprecedented opportunity to understand how organisms rapidly respond to strong anthropogenic-driven selection pressure. We recently identified agricultural populations of the grass species Bromus tectorum L. with resistance to multiple herbicides. To understand the evolutionary origins and spread of resistance, we investigated the resistance mechanisms to acetolactate synthase (ALS) inhibitors and photosystem II inhibitors, two widely used herbicide modes of action, in 49 B. tectorum populations. We assessed the genetic diversity, structure and relatedness in a subset of 21 populations. Resistance to ALS inhibitors was associated with multiple nonsynonymous mutations in ALS, the target site gene, despite the relatively small geographic region where populations originated, suggesting ALS inhibitor resistance evolution occurred multiple times in the region. We also found evidence that mechanisms not related to the target site evolved and were common in the populations studied. Resistance to photosystem II inhibitors was confirmed in two populations and was conferred by nonsynonymous mutations in the plastid gene psbA. Population genomics analyses suggested that ALS resistance in most populations, at the nucleotide level, spread via gene flow, except for one population where we found evidence that Pro-197-His mutations may have evolved in three separate events. Our results suggest that both gene flow via pollen and/or seed dispersal and multiple local evolutionary events were involved in the spread of herbicide-resistant B. tectorum. Our results provide an empirical example of the rapid repeated evolution of a trait under strong anthropogenic selection and elucidate the evolutionary origins of herbicide resistance in a plant species of agricultural importance.}, } @article {pmid40341849, year = {2025}, author = {Neuhaus, D and Wendebourg, MJ and Deigendesch, N and Berger, C and Bauer, M and Haas, T and Scheurer, E and Schlaeger, R and Lenz, C}, title = {Exploring Potential Biomarkers for Amyotrophic Lateral Sclerosis Using Postmortem In Situ Magnetic Resonance Imaging.}, journal = {NMR in biomedicine}, volume = {38}, number = {6}, pages = {e70059}, doi = {10.1002/nbm.70059}, pmid = {40341849}, issn = {1099-1492}, support = {//Neuromuscular Research Association Basel/ ; //Stiftung zur Foerderung der gastroenterologischen und der allgemeinen klinischen Forschung sowie der medizinischen Bildauswertung/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnostic imaging/pathology ; *Biomarkers/metabolism ; Male ; *Magnetic Resonance Imaging ; Female ; Middle Aged ; Aged ; Brain/diagnostic imaging/pathology ; Autopsy ; }, abstract = {There is an urgent need for reliable magnetic resonance imaging (MRI) biomarkers for the diagnosis, prognosis or therapy management of amyotrophic lateral sclerosis (ALS). The aim of this study was to explore potential biomarkers for ALS by conducting postmortem (PM) in situ MRI, allowing for a non-invasive evaluation of the disease's end-stage without the effects of formalin fixation. PM in situ MRI whole-brain scans of five deceased patients with clinically definite ALS and seven deceased healthy controls (HC) without known neurological disorders were performed at 3 Tesla. Fractional anisotropy, mean diffusivity, T1, T2 and T2* were assessed for cortex, deep grey matter, white matter, whole brain and hippocampus. For the validation of the MRI DTI data, the focus was placed on the hippocampus, where the myelin density was evaluated by analysing histological samples from the dentate gyrus. A custom python script was developed for the quantification of the myelin density in histological data. Comparing ALS to HC values suggested potential reductions of mean diffusivity, T1 (after outlier removal) and T2* in white matter and of T2 in deep grey matter in the ALS group. Furthermore, mean diffusivity was potentially reduced in the hippocampus of patients with ALS (after outlier removal), whereas no difference in myelin density was found by histopathological assessment. The results of this exploratory study suggest potential differences in diffusivity and relaxometry between PM in situ brains of patients with ALS and HC. Understanding these variations at the end-stage of ALS might contribute to the development of novel MRI prognostic and diagnostic biomarkers for ALS. However, larger sample sizes and complementary histological examinations are needed to confirm these results and to clarify the underlying mechanisms.}, } @article {pmid40341287, year = {2025}, author = {Merler, M and Agurto, C and Peller, J and Roitberg, E and Taitz, A and Trevisan, MA and Navar, I and Berry, JD and Fraenkel, E and Ostrow, LW and Cecchi, GA and Norel, R}, title = {Clinical assessment and interpretation of dysarthria in ALS using attention based deep learning AI models.}, journal = {NPJ digital medicine}, volume = {8}, number = {1}, pages = {260}, pmid = {40341287}, issn = {2398-6352}, abstract = {Speech dysarthria is a key symptom of neurological conditions like ALS, yet existing AI models designed to analyze it from audio signal rely on handcrafted features with limited inference performance. Deep learning approaches improve accuracy but lack interpretability. We propose an attention-based deep learning AI model to assess dysarthria severity based on listener effort ratings. Using 2,102 recordings from 125 participants, rated by three speech-language pathologists on a 100-point scale, we trained models directly from recordings collected remotely. Our best model achieved R[2] of 0.92 and RMSE of 6.78. Attention-based interpretability identified key phonemes, such as vowel sounds influenced by 'r' (e.g., "car," "more"), and isolated inspiration sounds as markers of speech deterioration. This model enhances precision in dysarthria assessment while maintaining clinical interpretability. By improving sensitivity to subtle speech changes, it offers a valuable tool for research and patient care in ALS and other neurological disorders.}, } @article {pmid40340943, year = {2025}, author = {Kellett, EA and Bademosi, AT and Walker, AK}, title = {Molecular mechanisms and consequences of TDP-43 phosphorylation in neurodegeneration.}, journal = {Molecular neurodegeneration}, volume = {20}, number = {1}, pages = {53}, pmid = {40340943}, issn = {1750-1326}, mesh = {Humans ; *DNA-Binding Proteins/metabolism ; Phosphorylation/physiology ; Animals ; *Neurodegenerative Diseases/metabolism ; Amyotrophic Lateral Sclerosis/metabolism ; }, abstract = {Increased phosphorylation of TDP-43 is a pathological hallmark of several neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). However, the regulation and roles of TDP-43 phosphorylation remain incompletely understood. A variety of techniques have been utilized to understand TDP-43 phosphorylation, including kinase/phosphatase manipulation, phosphomimic variants, and genetic, physical, or chemical inducement in a variety of cell cultures and animal models, and via analyses of post-mortem human tissues. These studies have produced conflicting results: suggesting incongruously that TDP-43 phosphorylation may either drive disease progression or serve a neuroprotective role. In this review, we explore the roles of regulators of TDP-43 phosphorylation including the putative TDP-43 kinases c-Abl, CDC7, CK1, CK2, IKKβ, p38α/MAPK14, MEK1, TTBK1, and TTBK2, and TDP-43 phosphatases PP1, PP2A, and PP2B, in disease. Building on recent studies, we also examine the consequences of TDP-43 phosphorylation on TDP-43 pathology, especially related to TDP-43 mislocalisation, liquid-liquid phase separation, aggregation, and neurotoxicity. By comparing conflicting findings from various techniques and models, this review highlights both the discrepancies and unresolved aspects in the understanding of TDP-43 phosphorylation. We propose that the role of TDP-43 phosphorylation is site and context dependent, and includes regulation of liquid-liquid phase separation, subcellular mislocalisation, and degradation. We further suggest that greater consideration of the normal functions of the regulators of TDP-43 phosphorylation that may be perturbed in disease is warranted. This synthesis aims to build towards a comprehensive understanding of the complex role of TDP-43 phosphorylation in the pathogenesis of neurodegeneration.}, } @article {pmid40340620, year = {2025}, author = {Shen, D and Liu, A and Yang, X and Liu, Q and Liu, M and Cui, L}, title = {Exploring oculomotor challenges in amyotrophic lateral sclerosis: a comprehensive review.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {26}, number = {5-6}, pages = {478-484}, doi = {10.1080/21678421.2025.2501690}, pmid = {40340620}, issn = {2167-9223}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology/complications/diagnosis ; *Ocular Motility Disorders/etiology/physiopathology/diagnosis ; *Eye Movements/physiology ; Disease Progression ; *Cognitive Dysfunction/physiopathology/etiology ; }, abstract = {Traditionally understood as a motor neuron disease, amyotrophic lateral sclerosis (ALS) is now recognized to involve broader neurodegenerative processes, including the oculomotor system. This narrative review summarizes current evidence on oculomotor dysfunction in ALS, with a focus on its relationship to disease-related motor and cognitive impairments. Specifically, the review examines key eye-tracking (ET) metrics, including saccades, smooth pursuit, and fixation, highlighting their potential to reflect both motor and extramotor degeneration. Notably, patients with bulbar-onset ALS exhibit more pronounced oculomotor impairments. By synthesizing findings on the connection between oculomotor dysfunction and cognitive decline, this review underscores the potential of ET as a noninvasive tool for assessing ALS progression. Oculomotor metrics, as part of a broader understanding of ALS's impact on multiple neural networks, may offer valuable insights to refine patient assessment and care strategies, particularly in advanced disease stages.}, } @article {pmid40340591, year = {2025}, author = {Ward, AL and Nooijen, C and Bernstein, J}, title = {Power wheelchair users with ALS: Impact of an alerting system on complications with prolonged sitting and power feature utilization.}, journal = {Assistive technology : the official journal of RESNA}, volume = {}, number = {}, pages = {1-10}, doi = {10.1080/10400435.2025.2497865}, pmid = {40340591}, issn = {1949-3614}, abstract = {An interventional technology called Virtual Seating Coach (VSC) provided alerts via an app to perform pressure redistribution using power wheelchair seat functions. The objective was whether alerts can contribute to more function utilization and thereby reduce pressure injuries and pain. Thirty-nine individuals with Amyotrophic Lateral Sclerosis (ALS) participated, 14 consented to use VSC, and 25 controls. The duration of the study was 27 months, with follow-up at 1 month or 3 months. Due to multiple technological and disease-related difficulties, three of those consented for the VSC received alerts once per hour to move into prescribed positions for one minute. These participants were able to use the VSC through the study end, and two of the three adhered to performing pressure redistribution after receiving alerts. The three using the VSC did not report pressure injuries; 12 of 21 controls reported development of a pressure injury. Furthermore, those using VSC noted a decrease in pain; most controls showed an increase during the same time period. The study thus highlighted the potential for such alerting technology while at the same time revealing many limitations due to disease progression and diminishing access to wheelchair controls.}, } @article {pmid40339618, year = {2025}, author = {Zhou, C and Hardin, EJ and Zimmer, TS and Jackvony, S and Barnett, D and Khobrekar, N and Giacomelli, E and Studer, L and Orr, AL and Orr, AG}, title = {Neuroimmune signaling mediates astrocytic nucleocytoplasmic disruptions and stress granule formation associated with TDP-43 pathology.}, journal = {Neurobiology of disease}, volume = {211}, number = {}, pages = {106939}, pmid = {40339618}, issn = {1095-953X}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; R01 NS118569/NS/NINDS NIH HHS/United States ; F31 AG079616/AG/NIA NIH HHS/United States ; RF1 NS118569/NS/NINDS NIH HHS/United States ; F31 AG084165/AG/NIA NIH HHS/United States ; T32 GM152349/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; *Astrocytes/metabolism/pathology/immunology ; Mice ; *DNA-Binding Proteins/metabolism/genetics ; *Signal Transduction/physiology ; Humans ; *Stress Granules/metabolism/pathology/immunology ; NF-kappa B/metabolism ; Mice, Inbred C57BL ; *Neuroimmunomodulation/physiology ; *TDP-43 Proteinopathies/pathology/metabolism/immunology ; }, abstract = {Alterations in transactivating response region DNA-binding protein 43 (TDP-43) are prevalent in amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and other neurological disorders. TDP-43 influences neuronal functions and might also affect glial cells. However, specific intracellular effects of TDP-43 alterations on glial cells and underlying mechanisms are not clear. We report that TDP-43 dysregulation in mouse and human cortical astrocytes causes nucleoporin mislocalization, nuclear envelope remodeling, and changes in nucleocytoplasmic protein transport. These effects are dependent on interleukin-1 (IL-1) receptor activity and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling and are associated with the formation of cytoplasmic stress granules. Stimulation of IL-1 receptors and NF-κB signaling are necessary and sufficient to induce astrocytic stress granules and rapid nucleocytoplasmic changes, which are broadly alleviated by inhibition of the integrated stress response. These findings establish that TDP-43 alterations and neuroimmune factors can induce nucleocytoplasmic changes through NF-κB signaling, revealing mechanistic convergence of proteinopathy and neuroimmune pathways onto glial nucleocytoplasmic disruptions that may occur in diverse neurological conditions.}, } @article {pmid40339566, year = {2025}, author = {Parameswaran, J and McEachin, ZT}, title = {PI3P: Rising to the (DPR) challenge in C9-ALS/FTD.}, journal = {Neuron}, volume = {113}, number = {9}, pages = {1301-1303}, doi = {10.1016/j.neuron.2025.04.007}, pmid = {40339566}, issn = {1097-4199}, mesh = {*Amyotrophic Lateral Sclerosis/genetics/metabolism ; *Frontotemporal Dementia/genetics/metabolism ; Humans ; C9orf72 Protein ; *Phosphatidylinositol Phosphates/metabolism ; *DNA Repeat Expansion/genetics ; *Proteins/genetics ; Animals ; *Dipeptides/genetics/metabolism ; }, abstract = {A hexanucleotide G4C2 repeat expansion in C9orf72 causes accumulation of dipeptide repeat (DPR) proteins and is the leading genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). In a recent issue of Neuron, Zhang et al.[1] report that elevating PI3P levels mitigates endolysosomal deficits and DPR-associated neurotoxicity.}, } @article {pmid40338888, year = {2025}, author = {Faisal, M and Khosa, I and Waris, A and Gilani, SO and Khan, MJ and Hazzazi, F and Ijaz, MA}, title = {Optimizing the impact of time domain segmentation techniques on upper limb EMG decoding using multimodal features.}, journal = {PloS one}, volume = {20}, number = {5}, pages = {e0322580}, pmid = {40338888}, issn = {1932-6203}, mesh = {Humans ; *Electromyography/methods ; *Upper Extremity/physiology ; Male ; Adult ; Female ; Movement/physiology ; Signal Processing, Computer-Assisted ; Support Vector Machine ; Young Adult ; }, abstract = {Neurological disorders, such as stroke, spinal cord injury, and amyotrophic lateral sclerosis, result in significant motor function impairments, affecting millions of individuals worldwide. To address the need for innovative and effective interventions, this study investigates the efficacy of electromyography (EMG) decoding in improving motor function outcomes. While existing literature has extensively explored classifier selection and feature set optimization, the choice of preprocessing technique, particularly time-domain windowing techniques, remains understudied posing a significant knowledge gap. This study presents upper limb movement classification by providing a comprehensive comparison of eight time-domain windowing techniques. For this purpose, the EMG data from volunteers is recorded involving fifteen distinct movements of fingers. The rectangular window technique among others emerged as the most effective, achieving a classification accuracy of 99.98% while employing 40 time-domain features and a L-SVM classifier, among other classifiers. This optimal combination has implications for the development of more accurate and reliable myoelectric control systems. The achieved high classification accuracy demonstrates the feasibility of using surface EMG signals for accurate upper limb movement classification. The study's results have the potential to improve the accuracy and reliability of prosthetic limbs and wearable sensors and inform the development of personalized rehabilitation programs. The findings can contribute to the advancement of human-computer interaction and brain-computer interface technologies.}, } @article {pmid40338003, year = {2025}, author = {Chen, X and Chen, X and Lin, X and Zhou, W and Hu, H and Jiang, H}, title = {Unveiling ten novel SETX mutations: implications for ALS pathogenesis and clinical diversity.}, journal = {Somatosensory & motor research}, volume = {}, number = {}, pages = {1-8}, doi = {10.1080/08990220.2025.2500940}, pmid = {40338003}, issn = {1369-1651}, abstract = {OBJECTIVE: To investigate the relationship between newly identified senataxin (SETX) gene mutations and the clinical manifestation of Amyotrophic Lateral Sclerosis (ALS), enhancing understanding of the genetic underpinnings associated with this disorder.

METHODS: A cohort study was conducted at Nanfang Hospital, involving comprehensive genetic sequencing of ALS patients to identify novel SETX mutations. Homology modelling and structural analysis were employed to predict the functional impacts of these mutations on the senataxin protein. Clinical assessments, including symptom evaluation, age of onset, and progression rate, were integrated with electrophysiological studies to establish correlations between genetic variants and clinical outcomes.

RESULTS: Ten novel SETX mutations were identified, expanding the genetic landscape of ALS. These mutations exhibited diverse impacts on clinical presentations, with patients showing variability in onset age, symptom severity, and progression rates. Computational modelling suggested that certain mutations cause significant structural changes in senataxin, potentially affecting its RNA/DNA helicase function. Electrophysiological findings consistently revealed nerve conduction abnormalities, indicating that these mutations may influence neuronal excitability and contribute to ALS pathogenesis.

CONCLUSION: The discovery of novel SETX mutations provides valuable insights into the genetic and clinical complexity of ALS. This study underscores the importance of genetic screening for SETX mutations and suggests potential personalised therapeutic approaches targeting senataxin dysfunction. By elucidating genotype-phenotype correlations, these findings contribute to the broader understanding of ALS and offer pathways for developing targeted interventions to address the challenges posed by this disabling disease.}, } @article {pmid40335898, year = {2025}, author = {Kim, JH and Whitaker, VM and Lee, S}, title = {A haplotype-phased genome characterizes the genomic architecture and causal variants for RXf1 conferring resistance to Xanthomonas fragariae in strawberry (F. × ananassa).}, journal = {BMC genomics}, volume = {26}, number = {1}, pages = {453}, pmid = {40335898}, issn = {1471-2164}, support = {#2022-51181-38328//National Institute of Food and Agriculture/ ; #2022-51181-38328//National Institute of Food and Agriculture/ ; #2022-51181-38328//National Institute of Food and Agriculture/ ; }, mesh = {*Fragaria/genetics/microbiology ; *Disease Resistance/genetics ; *Haplotypes ; *Plant Diseases/microbiology/genetics ; *Xanthomonas/physiology ; *Genome, Plant ; Chromosome Mapping ; *Genomics ; Chromosomes, Plant/genetics ; }, abstract = {BACKGROUND: Cultivated octoploid strawberry (Fragaria × ananassa) is one of the most economically important fruits worldwide due to its flavor, texture, and health benefits. However, bacterial angular leaf spot (ALS) causes economic losses in fruit production and plant nurseries. All commercial strawberry varieties are susceptible to ALS. A major resistance locus, RXf1, has been reported, but the genomic structure and candidate genes underlying this resistance remain known.

RESULTS: Fine-mapping was performed using three segregating populations containing 663 individuals that were genotyped with subgenome specific seven high-resolution melting (HRM) markers to narrow the RXf1 region to a 486-kb interval on chromosome 6C. We assembled a haplotype-phased chromosome-scale genome of ALS-resistant breeding selection FL17.68-110 using highly accurate long-read sequencing and trio-binning with parental short reads. The 1.62 Gbp genome containing two haplotypes, 56 chromosomes and 193,072 annotated genes. Transcriptome analysis in response to the ALS pathogen identified a candidate gene, Resistance gene analogue 3 (RGA3), associated with the RXf1 resistance. The gene structure and sequence variations within FaRGA3 were identified between resistant and susceptible genotypes.

CONCLUSIONS: Our results narrowed the RXf1 region, identified structural variations within this locus and pointed to FaRGA3 as a promising candidate gene. This information will be useful for breeders toward developing ALS-resistant strawberry varieties, and the high-quality genome will be a valuable resource for further genomics research in octoploid strawberry.}, } @article {pmid40334920, year = {2025}, author = {Perez, OD and Lin, MJ and Pomeranz, MK and Chiu, ES and Lu, CP and Petukhova, L}, title = {Response to Andersen et al's "A genome-wide association meta-analysis links hidradenitis suppurativa to common and rare sequence variants causing disruption of the Notch and Wnt/β-catenin signaling pathways".}, journal = {Journal of the American Academy of Dermatology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jaad.2025.04.064}, pmid = {40334920}, issn = {1097-6787}, } @article {pmid40334711, year = {2025}, author = {Sucker, C and Koscielny, J and Kappert, G}, title = {Ausgewählte Beiträge der BDDH-Veranstaltung im Rahmen der 69. Jahrestagung der Gesellschaft für Thrombose- und Hämostaseforschung (GTH) am 18.02.2025 in Lausanne.}, journal = {Hamostaseologie}, volume = {45}, number = {2}, pages = {209-211}, doi = {10.1055/a-2447-6517}, pmid = {40334711}, issn = {2567-5761}, mesh = {Humans ; *Hemostasis ; *Thrombosis ; }, abstract = {DHR -2025, WAS GIBT ES NEUES?: Die DHR-Webseite (www.pei.de/DE/regulation/melden/dhr/dhr-node.html) beinhaltet neben fünf Publikationen, die letzte von 2020, einen Jahresbericht 2022/2023. Die Daten aus 2023 sind als vorläufig gekennzeichnet. Veröffentlicht sind die Anzahlen gemeldeter Fälle (Hämophilie A/B nach Schweregrad, von Willebrand Syndrom Typ 3 und andere, seltene Faktoren und Hemmkörper bei Kindern und Erwachsenen), sowie der Verbrauch bis 2022. Klinisch relevante Daten, wie z.B. Blutungen, die Teil der Einzelmeldung sind, finden sich nicht.}, } @article {pmid40333935, year = {2025}, author = {Vanderlinden, G and Carron, C and Van Weehaeghe, D and De Vocht, J and Ombelet, F and Masrori, P and De Weerdt, C and James, RE and Evans, LT and Schroeder, FA and Hooker, JM and Koole, M and Kranz, JE and Gilbert, TM and Van Damme, P and Van Laere, K}, title = {Histone Deacetylase 6 Brain PET in Amyotrophic Lateral Sclerosis-Frontotemporal Spectrum Disorder.}, journal = {Annals of clinical and translational neurology}, volume = {12}, number = {7}, pages = {1350-1359}, pmid = {40333935}, issn = {2328-9503}, support = {//Association for Frontotemporal Degeneration/ ; //Target ALS/ ; //Eikonizo Therapeutics/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnostic imaging/metabolism ; Middle Aged ; Female ; Male ; *Positron-Emission Tomography/methods ; Aged ; *Histone Deacetylase 6/metabolism ; *Frontotemporal Dementia/diagnostic imaging/metabolism ; *Brain/diagnostic imaging/metabolism ; *Cognitive Dysfunction/diagnostic imaging/metabolism/etiology ; }, abstract = {OBJECTIVE: [[18]F]EKZ-001 is a positron emission tomography (PET) tracer targeting histone deacetylase 6 (HDAC6), an enzyme responsible for intracellular transport and clearance of misfolded proteins. HDAC6 modulation is a promising treatment strategy in neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS). Apart from motor symptoms, people with ALS (pwALS) can show a variable degree of cognitive impairment as part of the ALS-frontotemporal spectrum disorder (ALS-FTSD). This work assessed [[18]F]EKZ-001 binding in pwALS with variable involvement of FTSD.

METHODS: Twenty-four pwALS (13M/11F, 61 ± 10 years) and 12 healthy controls (HC) (6M/6F, 58 ± 3 years) were included. Thirteen pwALS were cognitively normal (ALS-CN), and eleven pwALS presented with FTSD (ALS-FTSD) ranging from mild cognitive or behavioral impairment to FTD, according to their performance on the Edinburgh cognitive and behavioral ALS screen (ECAS). All subjects underwent dynamic PET-MR imaging with arterial sampling, and regional distribution volumes (VT) were calculated using a Logan graphical analysis.

RESULTS: [[18]F]EKZ-001 VT was significantly lower in pwALS compared to HC. For ALS-CN, the largest reduction was found in the brainstem. For ALS-FTSD, reductions were more widespread in both gray and white matter. No differences in VT were found between pwALS with and without a C9orf72 mutation. [[18]F]EKZ-001 VT was not correlated with ECAS scores, age, or disease duration.

INTERPRETATION: [[18]F]EKZ-001 binding is lower throughout the brain in pwALS compared to HC. This may be related to a compensatory mechanism to repair intracellular transport defects in ALS or to reduced HDAC6 enzyme availability for [[18]F]EKZ-001 binding due to sequestration of HDAC6 within protein aggregates.}, } @article {pmid40333317, year = {2025}, author = {Simula, ER and Jasemi, S and Cossu, D and Fais, M and Cossu, I and Chessa, V and Canu, M and Sechi, LA}, title = {Human Endogenous Retroviruses as Novel Therapeutic Targets in Neurodegenerative Disorders.}, journal = {Vaccines}, volume = {13}, number = {4}, pages = {}, pmid = {40333317}, issn = {2076-393X}, support = {PNRR-MCNT1-2023-12376993//Ministero della Salute/ ; 2022BP837R//MUR, PRIN 2022/ ; 22//Regione Autonoma Sardegna grant: legge regionale 12 22 December 2022/ ; e.INS Ecosystem of Innovation for Next Generation Sardinia spoke n 5//European Union/ ; }, abstract = {Human Endogenous Retroviruses comprise approximately 8% of the human genome, serving as fragments of ancient retroviral infections. Although they are generally maintained in a silenced state by robust epigenetic mechanisms, specific HERV groups, particularly HERV-W and HERV-K, can become derepressed under specific pathological conditions, thereby contributing to the initiation and progression of neuroinflammatory and neurodegenerative processes. Preclinical studies and clinical trials, such as those investigating monoclonal antibodies, indicate that directly targeting these elements may offer a novel therapeutic strategy. In this review, we provide an overview of HERVs' biology, examine their role in neurodegenerative diseases such as amyotrophic lateral sclerosis, multiple sclerosis, Alzheimer's disease, and Parkinson's disease, and explore their therapeutic prospects, highlighting both the challenges and the potential future research directions needed to translate these approaches into clinical interventions.}, } @article {pmid40332510, year = {2025}, author = {Stacchiotti, C and Mazzella di Regnella, S and Cinotti, M and Spalloni, A and Volpe, E}, title = {Neuroinflammation and Amyotrophic Lateral Sclerosis: Recent Advances in Anti-Inflammatory Cytokines as Therapeutic Strategies.}, journal = {International journal of molecular sciences}, volume = {26}, number = {8}, pages = {}, pmid = {40332510}, issn = {1422-0067}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy/metabolism/pathology/immunology ; *Cytokines/therapeutic use/metabolism ; Animals ; *Neuroinflammatory Diseases/drug therapy/metabolism/pathology ; *Anti-Inflammatory Agents/therapeutic use/pharmacology ; Blood-Brain Barrier/metabolism ; Inflammation ; }, abstract = {Neuroinflammation is an inflammatory response occurring within the central nervous system (CNS). The process is marked by the production of pro-inflammatory cytokines, chemokines, small-molecule messengers, and reactive oxygen species. Microglia and astrocytes are primarily involved in this process, while endothelial cells and infiltrating blood cells contribute to neuroinflammation when the blood-brain barrier (BBB) is damaged. Neuroinflammation is increasingly recognized as a pathological hallmark of several neurological diseases, including amyotrophic lateral sclerosis (ALS), and is closely linked to neurodegeneration, another key feature of ALS. In fact, neurodegeneration is a pathological trigger for inflammation, and neuroinflammation, in turn, contributes to motor neuron (MN) degeneration through the induction of synaptic dysfunction, neuronal death, and inhibition of neurogenesis. Importantly, resolution of acute inflammation is crucial for avoiding chronic inflammation and tissue destruction. Inflammatory processes are mediated by soluble factors known as cytokines, which are involved in both promoting and inhibiting inflammation. Cytokines with anti-inflammatory properties may exert protective roles in neuroinflammatory diseases, including ALS. In particular, interleukin (IL)-10, transforming growth factor (TGF)-β, IL-4, IL-13, and IL-9 have been shown to exert an anti-inflammatory role in the CNS. Other recently emerging immune regulatory cytokines in the CNS include IL-35, IL-25, IL-37, and IL-27. This review describes the current understanding of neuroinflammation in ALS and highlights recent advances in the role of anti-inflammatory cytokines within CNS with a particular focus on their potential therapeutic applications in ALS. Furthermore, we discuss current therapeutic strategies aimed at enhancing the anti-inflammatory response to modulate neuroinflammation in this disease.}, } @article {pmid40332015, year = {2025}, author = {Duță, C and Dogaru, CB and Muscurel, C and Stoian, I}, title = {Nanozymes: Innovative Therapeutics in the Battle Against Neurodegenerative Diseases.}, journal = {International journal of molecular sciences}, volume = {26}, number = {8}, pages = {}, pmid = {40332015}, issn = {1422-0067}, mesh = {Humans ; *Neurodegenerative Diseases/drug therapy/metabolism ; Oxidative Stress/drug effects ; Animals ; Antioxidants/therapeutic use/chemistry/pharmacology ; *Nanostructures/chemistry/therapeutic use ; Reactive Oxygen Species/metabolism ; }, abstract = {Neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS) and Huntington's disease (HD), represent a significant challenge to global health due to their progressive nature and the absence of curative treatments. These disorders are characterized by oxidative stress, protein misfolding, and neuroinflammation, which collectively contribute to neuronal damage and death. Recent advancements in nanotechnology have introduced nanozymes-engineered nanomaterials that mimic enzyme-like activities-as promising therapeutic agents. This review explores the multifaceted roles of nanozymes in combating oxidative stress and inflammation in neurodegenerative conditions. By harnessing their potent antioxidant properties, nanozymes can effectively scavenge reactive oxygen species (ROS) and restore redox balance, thereby protecting neuronal function. Their ability to modify surface properties enhances targeted delivery and biocompatibility, making them suitable for various biomedical applications. In this review, we highlight recent findings on the design, functionality, and therapeutic potential of nanozymes, emphasizing their dual role in addressing oxidative stress and pathological features such as protein aggregation. This synthesis of current research underscores the innovative potential of nanozymes as a proactive therapeutic strategy to halt disease progression and improve patient outcomes in neurodegenerative disorders.}, } @article {pmid40331673, year = {2025}, author = {Ma, W and Dickie, A and Polgár, E and Yadav, M and Quillet, R and Gutierrez-Mecinas, M and Bell, AM and Todd, A}, title = {EXPRESS: Expression of Tacr1 and Gpr83 by spinal projection neurons.}, journal = {Molecular pain}, volume = {}, number = {}, pages = {17448069251342409}, doi = {10.1177/17448069251342409}, pmid = {40331673}, issn = {1744-8069}, abstract = {Anterolateral system (ALS) projection neurons underlie perception of pain, itch and skin temperature. These cells are heterogeneous, and there have therefore been many attempts to define functional populations. A recent study identified two classes of ALS neuron in mouse superficial dorsal horn (SDH) based on expression of the G protein-coupled receptors Tacr1 or Gpr83. It was reported that cells expressing these receptors formed largely non-overlapping populations, and that ~60% of ALS cells in SDH expressed Tacr1. An additional finding was that while Tacr1- and Gpr83-expressing ALS cells projected to several brain nuclei, their axons did not reach the ventral posterolateral (VPL) thalamic nucleus, which is reciprocally connected to the primary somatosensory cortex. These results were surprising, because we had reported that ~90% of SDH ALS neurons in the mouse possess the neurokinin 1 receptor (NK1r), which is encoded by Tacr1, and in addition the VPL is thought to receive input from lamina I ALS cells. Here we use retrograde and anterograde labelling in Tacr1CreERT2 and Gpr83CreERT2 mice to reinvestigate the expression of the receptors by ALS neurons and to reassess their projection patterns. We find that ~90% of ALS neurons in SDH express Tacr1, with 40-50% expressing Gpr83. We also show that axons of both Tacr1- and Gpr83-expressing ALS neurons reach the VPL. These results suggest that ALS neurons in the SDH that express these GPCRs show considerable overlap, and that they are likely to contribute to the sensory-discriminative dimension of pain through their projections to VPL.}, } @article {pmid40331424, year = {2025}, author = {Santoro, F and D'Amico, E and Brunetti, ND}, title = {Amyotrophic lateral sclerosis and Takotsubo syndrome: a call for action!.}, journal = {Journal of cardiovascular medicine (Hagerstown, Md.)}, volume = {26}, number = {5}, pages = {255-256}, doi = {10.2459/JCM.0000000000001724}, pmid = {40331424}, issn = {1558-2035}, } @article {pmid40330963, year = {2025}, author = {Kayabaşi, M and Köksaldi, S and Demirel, N and Saatci, AO}, title = {The Effect of Axial Length on Macular Vascular Density in Eyes with High Myopia.}, journal = {Romanian journal of ophthalmology}, volume = {69}, number = {1}, pages = {88-100}, pmid = {40330963}, issn = {2501-2533}, mesh = {Humans ; *Tomography, Optical Coherence/methods ; Female ; Male ; *Retinal Vessels/pathology/diagnostic imaging ; *Axial Length, Eye/pathology/diagnostic imaging ; Middle Aged ; Fluorescein Angiography/methods ; Adult ; *Myopia, Degenerative/diagnosis/physiopathology ; *Macula Lutea/blood supply/pathology ; Retrospective Studies ; Visual Acuity ; Fundus Oculi ; Choroid/blood supply/pathology ; Microvascular Density ; Fovea Centralis ; Follow-Up Studies ; }, abstract = {OBJECTIVE: To evaluate the relationship between optical coherence tomography angiography (OCTA) findings and axial length (AL) in eyes with high myopia.

MATERIALS AND METHODS: A total of 122 eyes from 78 patients were included. Seventy-five eyes with an AL ranging between 26.00 and 27.49 mm comprised Group 1, and 47 with an AL of ≥ 27.50 mm comprised Group 2. Spectral-domain OCT was performed to measure the central macular thickness, subfoveal choroidal thickness (SCT) and swept-source OCTA was utilized to obtain the data on foveal avascular zone (FAZ) and vascular density (VD) values at the superficial and deep capillary plexuses (SCP and DCP), outer retina (OuR), and choriocapillaris (CC) segments.

RESULTS: While no significant differences were found in terms of the mean superficial-FAZ and deep-FAZ areas (p=0.284 and p=0.952, respectively), there were significant differences between the groups in terms of the mean foveal VD in the SCP (p=0.001), the mean total VD (p=0.045) and foveal VD in the DCP (p<0.001), the mean foveal VD (p=0.019) and superior parafoveal VD in the OuR (p=0.008), the mean total (p=0.005), temporal parafoveal (p=0.034), inferior parafoveal (p=0.029), and nasal parafoveal VDs in the CC segments (p=0.005).

DISCUSSION: The findings of the present study highlight the complex interplay between axial elongation and retinal microvasculature, suggesting that factors beyond mechanical stretching may contribute to these alterations. The variability in the existing literature on this topic arises from inconsistencies in the definition of high myopia, the use of different OCTA devices, and heterogeneous study populations. By including eyes with myopic maculopathy and employing axial length-based classification, this study provides a broad representation of high myopia. However, its retrospective design, single-center setting, and monoracial cohort represent limitations. Future large-scale, prospective studies involving diverse populations are needed to elucidate further the pathophysiology of high myopia and its impact on retinal and choroidal microcirculation.

CONCLUSIONS: Our study revealed that high-myopic eyes with longer ALs exhibited increased total VD in the DCP and increased foveal VD in the SCP, DCP, and OuR segments, while they showed decreased total VD and temporal, inferior, and nasal parafoveal VDs in the CC segment compared to high-myopic eyes with shorter ALs.}, } @article {pmid40330290, year = {2025}, author = {Pérez-Holanda, S}, title = {Life-threatening bleeding caused by artery pseudoaneurysm after endoscopic procedure successfully treated by artery embolization.}, journal = {World journal of clinical cases}, volume = {13}, number = {13}, pages = {99278}, pmid = {40330290}, issn = {2307-8960}, abstract = {The Kakinuma et al's case report shows that non-pregnancy-related arterial pseudoaneurysm is a relatively rare, little known by some gynecologists, endoscopists, surgeons or radiologists, which can cause massive bleeding. Arterial pseudoaneurysm is a condition in which the wall of a blood vessel collapses due to some invasive event, and the resulting leaked blood is engulfed by soft tissues, forming a cavity that is in communication with the vessel. It is a potentially life-threatening complication that could occurs after some deliveries and some gynecological invasive procedures. Remarkably, an undetermined percentage of pseudoaneurysms are asymptomatic, and in an asymptomatic patient it is difficult to predict the risk of haemorrhage and the attitude to follow, which depends on several factors, such as, the size and location of the vessel involved, changes in the size of the pseudoaneurysm, or the available therapeutic resources to be offered to patients, among others circumstances. The management of abdominal arterial pseudoaneurysm does not have consistent scientific evidence, but it seems that, regardless of the associated circumstances, the pseudoaneurysm could be treated at least initially, and mainly, through endovascular procedures, as done by Kakinuma et al.}, } @article {pmid40329780, year = {2025}, author = {Mohammadi, S and Ghaderi, S and Fatehi, F and Kalra, S and Batouli, SAH}, title = {Pathological Aging of Patients With Amyotrophic Lateral Sclerosis: A Preliminary Longitudinal Study.}, journal = {Brain and behavior}, volume = {15}, number = {5}, pages = {e70484}, pmid = {40329780}, issn = {2162-3279}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology/pathology/diagnostic imaging/psychology ; Male ; Longitudinal Studies ; Female ; Middle Aged ; *Aging/pathology/physiology ; Aged ; Magnetic Resonance Imaging/methods ; *Brain/pathology/diagnostic imaging/physiopathology ; Neuropsychological Tests ; Cognition/physiology ; Cognitive Dysfunction/physiopathology ; Executive Function/physiology ; Disease Progression ; Adult ; }, abstract = {OBJECTIVE: This longitudinal study investigated pathological brain aging in amyotrophic lateral sclerosis (ALS) by evaluating disparities between chronological age and deep learning-derived brain structure age (BSA) and exploring associations with cognitive and functional decline.

METHODS: Ten limb-onset ALS patients (seven males) and 10 demographically matched healthy controls (HCs) underwent structural magnetic resonance imaging (sMRI) and cognitive assessments at baseline and follow-up. The BSA was estimated using the validated volBrain platform. Cognitive domains (language, verbal fluency, executive function, memory, and visuospatial skills) and global cognition (Persian adaptive Edinburgh Cognitive and Behavioral ALS Screen [ECAS] total score) were assessed along with functional status (ALSFRS-R).

RESULTS: ALS patients exhibited significant BSA-chronological age disparities at baseline (Δ = +7.31 years, p = 0.009) and follow-up (Δ = +8.39 years, p = 0.003), with accelerated BSA progression over time (p = 0.004). The HCs showed no such disparities (p = 0.931). Longitudinal BSA increases were correlated with executive function decline (r = -0.651, p = 0.042). Higher education predicted preserved language (r = 0.831, p = 0.003) and verbal fluency (r = 0.738, p = 0.015). ALSFRS-R decline paralleled visuospatial (r = 0.642, p = 0.045) and global cognitive deterioration (r = 0.667, p = 0.035).

CONCLUSIONS: ALS is characterized by accelerated structural brain aging that progresses independently of chronological age and is correlated with executive dysfunction. Education may mitigate cognitive decline, while motor functional deterioration aligns with visuospatial and global cognitive impairments. BSA has emerged as a potential biomarker for tracking pathological aging trajectories in ALS, warranting validation using larger cohorts.}, } @article {pmid40328798, year = {2025}, author = {Wu, X and Yang, Z and Zou, J and Gao, H and Shao, Z and Li, C and Lei, P}, title = {Protein kinases in neurodegenerative diseases: current understandings and implications for drug discovery.}, journal = {Signal transduction and targeted therapy}, volume = {10}, number = {1}, pages = {146}, pmid = {40328798}, issn = {2059-3635}, support = {32070961//National Natural Science Foundation of China (National Science Foundation of China)/ ; }, mesh = {Humans ; *Neurodegenerative Diseases/drug therapy/enzymology/genetics/pathology ; *Drug Discovery ; *Protein Kinases/genetics/metabolism ; *Protein Kinase Inhibitors/therapeutic use ; Signal Transduction/drug effects/genetics ; Phosphorylation ; Animals ; }, abstract = {Neurodegenerative diseases (e.g., Alzheimer's, Parkinson's, Huntington's disease, and Amyotrophic Lateral Sclerosis) are major health threats for the aging population and their prevalences continue to rise with the increasing of life expectancy. Although progress has been made, there is still a lack of effective cures to date, and an in-depth understanding of the molecular and cellular mechanisms of these neurodegenerative diseases is imperative for drug development. Protein phosphorylation, regulated by protein kinases and protein phosphatases, participates in most cellular events, whereas aberrant phosphorylation manifests as a main cause of diseases. As evidenced by pharmacological and pathological studies, protein kinases are proven to be promising therapeutic targets for various diseases, such as cancers, central nervous system disorders, and cardiovascular diseases. The mechanisms of protein phosphatases in pathophysiology have been extensively reviewed, but a systematic summary of the role of protein kinases in the nervous system is lacking. Here, we focus on the involvement of protein kinases in neurodegenerative diseases, by summarizing the current knowledge on the major kinases and related regulatory signal transduction pathways implicated in diseases. We further discuss the role and complexity of kinase-kinase networks in the pathogenesis of neurodegenerative diseases, illustrate the advances of clinical applications of protein kinase inhibitors or novel kinase-targeted therapeutic strategies (such as antisense oligonucleotides and gene therapy) for effective prevention and early intervention.}, } @article {pmid40328546, year = {2025}, author = {Kleinerova, J and Tan, EL and Delaney, S and Smyth, M and Bede, P}, title = {Advances and research priorities in the respiratory management of ALS: Historical perspectives and new technologies.}, journal = {Revue neurologique}, volume = {181}, number = {6}, pages = {525-534}, doi = {10.1016/j.neurol.2025.04.008}, pmid = {40328546}, issn = {0035-3787}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy/complications/history ; *Biomedical Research/trends ; History, 19th Century ; History, 20th Century ; History, 21st Century ; Noninvasive Ventilation/methods ; Respiratory Insufficiency/therapy/etiology ; }, abstract = {Respiratory involvement has been identified as a cardinal feature of amyotrophic lateral sclerosis (ALS) since its earliest descriptions in the 19th century. Since these initial reports, considerable research has been undertaken to clarify the pathophysiology and progression rates associated with respiratory compromise and effective management strategies have been developed. Clinical trials routinely incorporate respiratory measures as study end points, non-invasive ventilation is now widely used in the home setting, cough-assist techniques are commonly used, advanced neurophysiology techniques and wearable technologies have been integrated into respiratory monitoring protocols, and palliative guidelines have been developed to effectively manage respiratory distress. Despite the widespread implementation of these interventions, epidemiology studies are inconsistent and some studies suggest that survival in ALS has not improved significantly with the introduction of these measures. The outcomes of diaphragmatic pacing trials have been disappointing, advanced neurophysiology techniques are not routinely utilised, spinal and brainstem imaging are not commonly undertaken and significant geographical differences exist in proceeding to tracheostomy. The worldwide COVID pandemic has given impetus for remote monitoring, connected devices, video-consultations, and timely vaccinations in ALS; lessons that are invaluable long after the pandemic. Respiratory monitoring and management in ALS is a swiftly evolving facet of ALS care with considerable quality of life benefits.}, } @article {pmid40328418, year = {2025}, author = {Lai, IC and Wei, JC}, title = {Comment on Kaltchenko et al's "Dupilumab and neuropsychiatric outcomes in pediatric atopic dermatitis: A real-world cohort analysis".}, journal = {Journal of the American Academy of Dermatology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jaad.2025.02.101}, pmid = {40328418}, issn = {1097-6787}, } @article {pmid40328131, year = {2025}, author = {Amorim, RM and Gaudie-Ley, LW and Aguiar, M and Sant'Anna, PDS and Freitas, ADS and Caetano, LF and Póvoa, AA and Santos, CSG and Folly, E and Silva, EC and Neto, JAB}, title = {The role of bioremediation in mitigating urban expansion impacts on coastal lagoons: A comparative study of Araçatiba and Padre Lagoons, Rio de Janeiro.}, journal = {Marine pollution bulletin}, volume = {217}, number = {}, pages = {118048}, doi = {10.1016/j.marpolbul.2025.118048}, pmid = {40328131}, issn = {1879-3363}, mesh = {Brazil ; *Biodegradation, Environmental ; *Environmental Monitoring ; Eutrophication ; Seawater/chemistry ; Geologic Sediments/chemistry ; Nitrogen/analysis ; Phosphorus/analysis ; Animals ; *Urban Renewal ; }, abstract = {This study examines the impact of urban expansion on organic matter gradients in two coastal lagoons, Araçatiba (AL) and Padre (PL), in Rio de Janeiro, Brazil, using benthic macrofauna as ecological indicators. To mitigate the effects of organic enrichment, a microbial consortium (Lactobacillus casei, Lactobacillus acidophilus, and Saccharomyces cerevisiae) was applied in AL for nine months prior to sampling, while PL remained untreated. Sediment samples were collected from 43 stations and analyzed for Total Organic Carbon (TOC), Total Nitrogen (TN), and Total Phosphorus (TP), alongside water column parameters (e.g., dissolved oxygen, salinity, chlorophyll-a) and benthic macrofaunal composition. Results indicated higher macrofaunal abundance and diversity in AL compared to PL, where organic pollution and eutrophication were more severe. Canonical Correspondence Analysis (CCA) identified salinity and eutrophication as primary drivers of community structure, with taxa such as Capitella spp. and Streblospio sp. tolerating high organic loads and hypoxia. AL's benthic community was dominated by mollusks (Heleobia australis, Mytilopsis leucophaeata), while PL was dominated by annelids (oligochaetes, Alitta succinea), reflecting divergent environmental conditions. The AMBI index classified PL as moderately to severely disturbed and AL as slightly to moderately disturbed, aligning with geochemical data showing higher TOC and nutrient concentrations in PL sediments. Microbial bioremediation in AL correlated with improved water quality (higher WQI, lower BOD) and benthic health, underscoring its potential as a management tool. The study highlights the need for tailored strategies to address anthropogenic pressures and restore ecological balance in coastal lagoons.}, } @article {pmid40328052, year = {2025}, author = {Mirveis, Z and Patil, N and Byrne, HJ}, title = {Exploring cellular metabolic kinetics through spectroscopic analysis of extracellular environments.}, journal = {Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy}, volume = {340}, number = {}, pages = {126308}, doi = {10.1016/j.saa.2025.126308}, pmid = {40328052}, issn = {1873-3557}, mesh = {Spectroscopy, Fourier Transform Infrared/methods ; Kinetics ; Glucose/metabolism/analysis ; Glutamine/metabolism ; Lactic Acid/metabolism/analysis ; Glycolysis ; Least-Squares Analysis ; Humans ; *Extracellular Space/metabolism ; }, abstract = {Studying the kinetics of metabolic pathways, such as glycolysis and glutaminolysis, is valuable due to their fundamental links to various diseases, including cancer. This study explores the potential of Attenuated Total Reflectance-Fourier Transform Infrared (ATR-FTIR) spectroscopy for analysing low concentrations of metabolites in extracellular media. It also evaluates the use of the Multivariate Curve Resolution-Alternating Least Squares (MCR-ALS) method to data mine the kinetic evolution of the spectroscopic signatures of the glycolysis metabolic pathway and to explore the impact of the presence of glutamine on it. By extracting samples at specific time intervals and drying them on the ATR crystal, ATR-FTIR could effectively measure individual metabolites of glucose, glutamine and lactate at low concentrations, providing clear spectra with strong correlations between peak absorbance and metabolite concentrations. In data mining, MCR-ALS successfully resolved two components, glucose and lactate, from time-series data of cellular glucose metabolism (glycolysis), showing approximately 28 % glucose consumption and 1 mM lactate production at a constant rate of 0.0016 min[-1]. However, when glutamine was introduced as a third component, the overlap of the peaks of glutamine and lactate limited the method's ability to deconvolute the data, highlighting constraints of MCR-ALS in complex mixtures.}, } @article {pmid40327885, year = {2025}, author = {Malik, T and Sidisky, JM and Jones, S and Winters, A and Hocking, B and Rotay, J and Huhulea, EN and Moran, S and Connors, B and Babcock, DT}, title = {Synaptic defects in adult drosophila motor neurons in a model of amyotrophic lateral sclerosis.}, journal = {Human molecular genetics}, volume = {34}, number = {14}, pages = {1204-1215}, doi = {10.1093/hmg/ddaf068}, pmid = {40327885}, issn = {1460-2083}, mesh = {*Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology/physiopathology ; Animals ; *Motor Neurons/metabolism/pathology ; Disease Models, Animal ; *RNA-Binding Protein FUS/genetics/metabolism ; *Synapses/metabolism/pathology/genetics ; Humans ; Drosophila/genetics ; Drosophila melanogaster/genetics ; Drosophila Proteins/genetics/metabolism ; Mutation ; Neuromuscular Junction ; Optogenetics ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that primarily affects motor neurons in the brain and spinal cord. Like other neurodegenerative diseases, defects in synaptic integrity are among the earliest hallmarks of ALS. However, the specific impairments to synaptic integrity remain unclear. To better understand synaptic defects in ALS, we expressed either wild-type or mutant Fused in Sarcoma (FUS), an RNA binding protein that is often mis-localized in ALS, in adult motor neurons. Using optogenetic stimulation of the motor neurons innervating the Ventral Abdominal Muscles (VAMs), we found that expression of mutant FUS disrupted the functional integrity of these synapses. This functional deficit was followed by disruption of synaptic gross morphology, localization of pre- and post-synaptic proteins, and cytoskeleton integrity. We found similar synaptic defects using the motor neurons innervating the Dorsal Longitudinal Muscles (DLMs), where expression of mutant FUS resulted in a progressive loss of flight ability along with disruption of active zone distribution. Our findings uncover defects in synaptic function that precede changes in synaptic structure, suggesting that synaptic function is more sensitive to this ALS model. Highlighting the earliest synaptic defects in this disease model should help to identify strategies for preventing later stages of disease progression.}, } @article {pmid40326917, year = {2025}, author = {van Eijk, RPA and Weemering, DN and Opie-Martin, S and van Unnik, JWJ and Caravaca Puchades, A and Chiò, A and Corcia, P and Galvin, M and Hardiman, O and Heverin, M and Hobin, F and Holmdahl, O and Ingre, C and Lamaire, N and Mac Domhnaill, É and McDonough, H and Manera, U and McDermott, CJ and McFarlane, R and Mouzouri, M and Ombelet, F and Povedano Panadés, M and Sennfält, S and Shaw, PJ and Terrafeta Pastor, C and Van Damme, P and Vasta, R and Veldink, JH and Al-Chalabi, A and van den Berg, LH}, title = {Natural history of the revised ALS functional rating scale and its association with survival: the PRECISION-ALS Extant Study.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {26}, number = {sup1}, pages = {30-40}, doi = {10.1080/21678421.2024.2443985}, pmid = {40326917}, issn = {2167-9223}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/mortality/diagnosis/physiopathology ; Male ; Female ; Middle Aged ; Disease Progression ; Aged ; Longitudinal Studies ; Cohort Studies ; Adult ; Severity of Illness Index ; Survival Rate/trends ; }, abstract = {OBJECTIVE: To characterize the natural history of the revised ALS functional rating scale (ALSFRS-R) over a 24-month period following initial assessment, and to assess its associations with survival.

METHODS: Longitudinal ALSFRS-R measurements and survival data were obtained from seven population-based, European cohorts. Different models for the ALSFRS-R trajectory were evaluated, including tests for linearity and between-cohort differences. We employed a joint modeling framework to factor in mortality, thereby aiming to derive a more precise estimate of the population's rate of decline, while simultaneously delineating its relationship with survival.

RESULTS: In total, 7,030 patients were included who produced 31,746 ALSFRS-R measurements during a follow-up period of 10,285 person-years. There was substantial evidence for a non-linear time trend within all cohorts (all p < 0.001), with faster progression rates at the beginning of follow-up. The average rate over 24 months was 0.89 points per month; 95% of the patients had a rate between 0.04 and 1.96. Overall, two components of the ALSFRS-R trajectory were found to be associated with survival: (1) the actual value of the ALSFRS-R total score and (2) the rate of change at any given time (both p < 0.001).

CONCLUSIONS: Functional loss in ALS follows a decelerating trajectory, where the current functional status and the rate of change have a direct impact on the patient' s probability of survival. Given the pivotal role of the ALSFRS-R in drug development, these results help to separate treatment benefit from the disease's natural trajectory and to estimate the impact on survival.}, } @article {pmid40326916, year = {2025}, author = {Sennfält, S and Al-Chalabi, A and Caravaca Puchades, A and Chiò, A and Corcia, P and Galvin, M and Hardiman, O and Heverin, M and Hobin, F and Holmdahl, O and Lamaire, N and Mac Domhnaill, É and McDonough, H and Manera, U and McDermott, CJ and McFarlane, R and Mouzouri, M and Ombelet, F and Opie-Martin, S and Povedano Panadés, M and Shaw, P and Terrafeta Pastor, C and Van Damme, P and van den Berg, L and van Eijk, RPA and Vasta, R and Veldink, JH and Weemering, DN and Ingre, C}, title = {Respiratory function, survival, and NIV prevalence over time in ALS - a PRECISION ALS study.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {26}, number = {sup1}, pages = {61-72}, doi = {10.1080/21678421.2025.2454923}, pmid = {40326916}, issn = {2167-9223}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/mortality/therapy/physiopathology/genetics/epidemiology/complications ; Male ; Female ; Middle Aged ; *Noninvasive Ventilation/statistics & numerical data/trends ; Aged ; Prevalence ; Prospective Studies ; *Respiratory Insufficiency/therapy/etiology ; Adult ; Disease Progression ; Cohort Studies ; C9orf72 Protein/genetics ; }, abstract = {INTRODUCTION: Respiratory function typically deteriorates as ALS progresses and is associated with shorter survival. This study aims to describe respiratory function and the prevalence of noninvasive ventilation (NIV) along the disease trajectory using prospective data from the PRECISION ALS project.

METHODS: We included 3449 ALS patients from six European population-based cohorts. All had comparable assessments of vital capacity, percent predicted (VC%) (58.1% had multiple assessments) and 56% had assessments of the revised ALS Functional Rating Scale (ALSFRS-R). The data were analyzed in relation to survival, NIV, and genetic status (C9orf72, SOD1, FUS, and TARDBP).

RESULTS: In those with a survival time of 1-4 years from diagnosis, the median VC% declined from 91 to 97% at the first assessment to 47-50% at the last assessment 6 months before death. In those with longitudinal assessments, the median VC% declined an average of 24 percentage points per year. Over time, there was an increase in respiratory symptoms relative to general functional impairment, as measured by the ALSFRS-R, and VC% was strongly associated with shorter survival. The confirmed prevalence of NIV was approximately 3%, 15%, and 25% in patients with a VC% of >80, 50-80, and <50, respectively.

CONCLUSION: There was a trend of worsening respiratory function over time and an increase in respiratory symptoms relative to general functional impairment. Survival was strongly associated with respiratory function. In those with impaired respiratory function, there was significant variation in the introduction of NIV.}, } @article {pmid40326915, year = {2025}, author = {Caravaca Puchades, A and McDonough, HE and Al-Chalabi, A and Chiò, A and Corcia, P and Galvin, M and Hardiman, O and Heverin, M and Hobin, F and Holmdahl, O and Ingre, C and Lamaire, N and Mac Domhnaill, É and Manera, U and McFarlane, R and Mouzouri, M and Ombelet, F and Opie-Martin, S and Sennfält, S and Terrafeta Pastor, C and Veldink, JH and Van Damme, P and van den Berg, L and van Eijk, RPA and Vasta, R and Weemering, DN and Shaw, P and McDermott, CJ and Povedano Panadés, M}, title = {Mapping the natural history of amyotrophic lateral sclerosis: time-to-event analysis of clinical milestones in the pan-European, population-based PRECISION-ALS cohort.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {26}, number = {sup1}, pages = {8-19}, doi = {10.1080/21678421.2024.2448535}, pmid = {40326915}, issn = {2167-9223}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/diagnosis/epidemiology/therapy/mortality ; Male ; Middle Aged ; Female ; Europe/epidemiology ; Aged ; Disease Progression ; Cohort Studies ; Age of Onset ; Prognosis ; Adult ; C9orf72 Protein/genetics ; Gastrostomy ; Noninvasive Ventilation ; Superoxide Dismutase-1/genetics ; }, abstract = {OBJECTIVE: Map time to key clinical milestones in amyotrophic lateral sclerosis (ALS), highlighting underlying genotypic and phenotypic prognostic factors.

BACKGROUND: Understanding the ALS disease trajectory and factors influencing the heterogeneous disease course is important to guide clinical care and stratify individuals to effectively assess therapeutics in clinical trials.

METHODS: Population-based datasets from nine European ALS care centers were collated. Time-to-event analysis was conducted for key clinical milestones: symptom onset, diagnosis, gastrostomy insertion, noninvasive ventilation (NIV) initiation, and survival. Independent prognostic factors were determined.

RESULTS: 21,820 people with ALS from nine ALS centers were included. Median age of symptom onset was 63.9 years. Median diagnostic delay was 1.0 years, with median survival of 33.7 months from onset. Prognostic factors for survival included age at onset, baseline vital capacity, progression rate, diagnostic delay, site of onset, and C9orf72-positive status. SOD1 variants D91A and G94C had protective prognostic effects in the whole cohort. Median time from diagnosis to gastrostomy insertion in bulbar-onset disease was 2.34 years. Median time from diagnosis to NIV initiation in those diagnosed between 2010 and 2019 was 3.61 years. Significant differences between ALS clinical center cohorts were seen in time to gastrostomy insertion, time to NIV initiation, and in overall survival time.

CONCLUSION: Our analysis of a large, well-defined, population-based European cohort provides detailed insight into the natural history of ALS, highlighting phenotypic and genetic factors affecting time to key clinical milestones. Further study is needed to determine the drivers in observed differences between ALS clinical center cohorts in time to clinical interventions and overall survival.}, } @article {pmid40326914, year = {2025}, author = {Vasta, R and Ombelet, F and Hobin, F and Manera, U and Ammar, AC and Caravaca Puchades, A and Corcia, P and Galvin, M and Hardiman, O and Heverin, M and Holmdahl, O and Ingre, C and Lamaire, N and McDermott, C and Mac Domhnaill, É and McDonough, H and McFarlane, R and Mouzouri, M and Sarah, OM and Povedano Panadés, M and Sennfält, S and Shaw, P and Terrafeta Pastor, C and van den Berg, LH and van Eijk, RPA and Veldink, JH and Weemering, DN and Van Damme, P and Chiò, A}, title = {Real-world prognostic role of riluzole use in ALS: a multi-center study from PRECISION-ALS.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {26}, number = {sup1}, pages = {50-60}, doi = {10.1080/21678421.2025.2472889}, pmid = {40326914}, issn = {2167-9223}, mesh = {Humans ; *Riluzole/therapeutic use ; *Amyotrophic Lateral Sclerosis/drug therapy/mortality/diagnosis ; Male ; Female ; Middle Aged ; *Neuroprotective Agents/therapeutic use ; Retrospective Studies ; Aged ; Prognosis ; Disease Progression ; Adult ; Kaplan-Meier Estimate ; Treatment Outcome ; }, abstract = {BACKGROUND: Amyotrophic Lateral Sclerosis (ALS) remains an incurable disease, with limited treatment options, and riluzole is the most widely available drug. We evaluated survival in a large cohort of patients with ALS, comparing those treated with riluzole to those who were not.

METHODS: Using data from the PRECISION-ALS database, we retrospectively analyzed patients with ALS who were treated with 100 mg of riluzole daily at the time of diagnosis. ALSFRS-R slope from onset to diagnosis (ΔFRS) was calculated. Based on the ΔFRS distribution, we defined fast progressors as patients having a ΔFRS > 1.17, intermediate progressors as those with 1.17 > ΔFRS > 0.31 and slow progressors as those with a ΔFRS < 0.31 points per month. We used Kaplan-Meier curves and Cox proportional hazards model to explore the association of riluzole use with patient survival since diagnosis.

RESULTS: Out of the 5842 patients with available riluzole data, 4847 (82.9%) received riluzole. The overall survival significantly differed between patients treated and not treated with riluzole (HR 0.70, 95%CI 0.69, 0.79), independently of sex, site of onset, age at onset and diagnostic delay. Patients treated with riluzole exhibited a 7 month longer median survival than those who did not receive riluzole (17.6 months, IQR 9.7, 29.9 vs 10.7 months, IQR 4.3, 23.4; p = 2 × 10[-16]). The relationship between riluzole use and extended survival varied across ΔFRS strata, being only evident among fast progressors (HR = 0.50, 95% 0.40, 0.63).

CONCLUSIONS: Treatment with riluzole is an independent prognostic factor in ALS. The extended survival related to riluzole use was only evident among fast-progressing patients.}, } @article {pmid40326913, year = {2025}, author = {McDonough, H and McFarlane, R and Caravaca Puchades, A and Chiò, A and Corcia, P and Galvin, M and Heverin, M and Hobin, F and Holmdahl, O and Ingre, C and Lamaire, N and Mac Domhnaill, É and Manera, U and Mouzouri, M and Ombelet, F and Opie-Martin, S and Povedano Panadés, M and Sennfält, S and Terrafeta Pastor, C and Veldink, JH and van Damme, P and van Den Berg, L and van Eijk, RPA and Vasta, R and Weemering, DN and Al-Chalabi, A and Shaw, P and McDermott, CJ and Hardiman, O}, title = {Examining changing working status and caregiver assistance in amyotrophic lateral sclerosis (ALS) using large-scale European databases as part of PRECISION-ALS.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {26}, number = {sup1}, pages = {20-29}, doi = {10.1080/21678421.2024.2448536}, pmid = {40326913}, issn = {2167-9223}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/epidemiology/psychology/therapy/nursing ; *Caregivers/psychology/statistics & numerical data ; Female ; Male ; Middle Aged ; Europe/epidemiology ; *Employment/statistics & numerical data/trends ; Aged ; Adult ; Databases, Factual ; Cohort Studies ; Longitudinal Studies ; }, abstract = {OBJECTIVE: To examine the working status of people living with ALS (plwALS), the identity of their caregivers, the amount of informal care provided to them, and how these factors change over time.

METHODS: Data from nine specialist European ALS centers and previously funded projects, such as ALSCarE, were collated. The cohort was stratified into progression groups based on the calculated ΔFRS and compared longitudinally.

RESULTS: Twenty-one thousand eight hundred and twenty patients were identified at the time of data analysis. One thousand one hundred and eighty-four had working status data. Two hundred and thirty-seven patients in this group were followed in the form of semi-structured interviews. Within the 1184 patient group, 45% were identified as in "paid employment" prior to diagnosis, taking a median of 12 months to leave the workforce post-onset. Eighty-three percent of patients were no longer working 20 months post-diagnosis. Informal care hours increased over time, and were primarily provided by spouses and children. In those less than 12 months from symptom onset, the median number of care hours per week was 15.0 (IQR 63.8), rising to 60.0 (IQR 154.0) 48-96 months after onset. There was a significant relationship between ALSFRS-R total score and hours of care delivered (r = -0.47, p < 0.001).

CONCLUSION: Up to 45% of plwALS are working prior to diagnosis and their working status changes rapidly, taking an average of 12 months to leave the workforce. Caregiver input increases over time, proportional to ALSFRS-R score. Caregivers are primarily spouses and children. Further work is needed to comprehensively capture this information and calculate its true socioeconomic impact.}, } @article {pmid40326912, year = {2025}, author = {McFarlane, R and Opie-Martin, S and Caravaca Puchades, A and Chiò, A and Corcia, P and Galvin, M and Heverin, M and Hobin, F and Holmdahl, O and Ingre, C and Lamaire, N and Mac Domhnaill, É and Manera, U and Mcdermott, CJ and McDonough, H and Mouzouri, M and Ombelet, F and Panadés, MP and Sennfält, S and Shaw, P and Terrafeta Pastor, C and Veldink, JH and Van Damme, P and van den Berg, L and Van Eijk, RPA and Vasta, R and Weemering, DN and Al-Chalabi, A and Hardiman, O}, title = {Clinical trajectories of genetic variants in ALS: a European observational study within PRECISION-ALS.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {26}, number = {sup1}, pages = {41-49}, doi = {10.1080/21678421.2025.2450805}, pmid = {40326912}, issn = {2167-9223}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/epidemiology/diagnosis ; Male ; Female ; *C9orf72 Protein/genetics ; Middle Aged ; *RNA-Binding Protein FUS/genetics ; Europe/epidemiology ; *Superoxide Dismutase-1/genetics ; Aged ; *DNA-Binding Proteins/genetics ; *Genetic Variation/genetics ; Adult ; Age of Onset ; Registries ; Genetic Testing ; }, abstract = {OBJECTIVE: To investigate the association between C9orf72, SOD1, FUS and TARDBP variants on the clinical trajectory of ALS patients in Europe.

METHODS: Nine ALS centers with population-based registries provided data on demographic and disease characteristics - at diagnosis and longitudinally - as part of PRECISION ALS. These data were harmonized and collated for analysis.

RESULTS: 21,820 ALS patients were identified, 9,887 underwent genetic testing for at least one of the 4 genes of interest. 9.8% of patients carried a hexanucleotide expansion in C9orf72; 2.9% carried a pathogenic variant in SOD1; 1.4% carried a pathogenic variant in TARDBP; and 0.8% carried a pathogenic variant in FUS. Only one p.A5V variant was identified in this dataset. The most frequently identified SOD1 variant was p.D91A, with evidence of other variant clusters in Belgium, Italy and the United Kingdom. TARDBP variants were clustered in the Netherlands and Italy. Earlier ages of onset were demonstrated compared to wild-type populations; C9orf72 59.58 (IQR 62.5, p < 2.2e-16), SOD1 54.19 (IQR 19.4, p = 6.304e-14), TARDBP 58.30 (IQR 16.23, p = 0.00024) and FUS 51.16 (IQR 25.08, p = 1.58e-06). C9orf72 was more bulbar (p < 0.0001) in onset and SOD1 more spinal (p < 0.0001). Those carrying variants spent distinctly different periods in each of the King's stages.

CONCLUSIONS: Genetic forms of ALS have an earlier age of onset, have distinct patterns in their sites of disease onset, and progress differently as compared to populations without such major-effect genes. There is also evidence of disease clusters across Europe suggestive of founder effects.}, } @article {pmid40326218, year = {2025}, author = {Yan, G and Tang, H and Shen, Y and Han, L and Han, Q}, title = {AI-Generated Ammonium Ligands for High-Efficiency and Stable 2D/3D Heterojunction Perovskite Solar Cells.}, journal = {Advanced materials (Deerfield Beach, Fla.)}, volume = {37}, number = {26}, pages = {e2503154}, doi = {10.1002/adma.202503154}, pmid = {40326218}, issn = {1521-4095}, support = {2020YFB1506400//National Key R&D Program of China/ ; 2021YFB3800100//National Key R&D Program of China/ ; U20A20245//National Natural Science Foundation of China/ ; U21A20171//National Natural Science Foundation of China/ ; 11834011//National Natural Science Foundation of China/ ; 12074245//National Natural Science Foundation of China/ ; }, abstract = {The 2D/3D heterojunction perovskite solar cells (PSCs) exhibit remarkable stability, but the quantum well in the 2D perovskite capping layer hinders the carrier transport, thereby lowering the power conversion efficiency (PCE). The relationship between the transport barrier and the complex structure of ammonium ligands (ALs) is currently poorly understood, thus leading to the one-sided approach and inefficient process in the development of 2D perovskite. Here, a machine learning procedure is established to comprehensively explore the relationship and combined it with an artificial intelligence (AI) model based on reinforcement learning algorithm to accelerate the generation of ALs. Finally, the AI-designed ALs improved the carrier transport performance of the 2D perovskite capping layer, and we achieved a certified PCE of 26.12% in inverted PSCs. The devices retained 96.79% of the initial PCE after 2000 h operation in maximum power point tracking under 1-sun illumination at 85°C.}, } @article {pmid40325332, year = {2025}, author = {Liu, S and Feng, A and Li, Z}, title = {Neuron-Derived Extracellular Vesicles: Emerging Regulators in Central Nervous System Disease Progression.}, journal = {Molecular neurobiology}, volume = {}, number = {}, pages = {}, pmid = {40325332}, issn = {1559-1182}, abstract = {The diagnosis and exploration of central nervous system (CNS) diseases remain challenging due to the blood-brain barrier (BBB), complex signaling pathways, and heterogeneous clinical manifestations. Neurons, as the core functional units of the CNS, play a pivotal role in CNS disease progression. Extracellular vesicles (EVs), capable of crossing the BBB, facilitate intercellular and cell-extracellular matrix (ECM) communication, making neuron-derived extracellular vesicles (NDEVs) a focal point of research. Recent studies reveal that NDEVs, carrying various bioactive substances, can exert either pathogenic or protective effects in numerous CNS diseases. Additionally, NDEVs show significant potential as biomarkers for CNS diseases. This review summarizes the emerging roles of NDEVs in CNS diseases, including Alzheimer's disease, depression, traumatic brain injury, schizophrenia, ischemic stroke, Parkinson's disease, amyotrophic lateral sclerosis, and multiple sclerosis. It aims to provide a novel perspective on developing therapeutic and diagnostic strategies for CNS diseases through the study of NDEVs.}, } @article {pmid40324968, year = {2025}, author = {Gomathy, SB and Macken, WL and Rani, N and Agarwal, A and Singh, R and Dhamne, M and Nair, SS and Reyaz, A and Ahmed, T and Dalal, A and Muthulakshmi, M and Wilson, L and Vijayaraghavan, A and , and Bhatia, R and Pitceathly, RDS and Thangaraj, K and Reilly, MM and Srivastava, PM and Hanna, MG and Vishnu, VY}, title = {Kennedy's disease from India: An Indian Cohort with multisystemic manifestations.}, journal = {Journal of neuromuscular diseases}, volume = {12}, number = {4}, pages = {513-522}, doi = {10.1177/22143602251325795}, pmid = {40324968}, issn = {2214-3602}, mesh = {Humans ; Male ; India ; Middle Aged ; Adult ; Retrospective Studies ; *Bulbo-Spinal Atrophy, X-Linked/genetics/physiopathology/complications/diagnosis ; Cohort Studies ; }, abstract = {BackgroundKennedy's disease (KD) is a rare, insidiously progressive lower motor neuron syndrome characterised by amyotrophy involving the appendicular or bulbar musculature of adult males in their fourth to fifth decade. There are no large series from the Indian subcontinent describing the clinical-genetic and laboratory spectrum of KD.AimTo describe the clinical, electrophysiologic, metabolic and genetic profile of patients with KD.MethodsWe conducted a retrospective review of ten genetically confirmed KD patients.ResultsThe mean age of the cohort was 47 years, with a mean age of onset of illness at 41.3 ± 9.9 years. The median duration of symptoms before presentation was 5 (3-12) years. The most common referral diagnosis was ALS. The majority presented with symmetric proximal limb weakness with bulbar symptoms and were found to have gynecomastia, lower motor neuron (LMN) facial weakness, and facial and lingual fasciculations. Electrophysiology revealed sensory neuropathy in five patients and chronic neurogenic changes consistent with anterior horn cell disease in all. Metabolic profile showed impaired glycemia, hyperlipidemia and evidence of non-alcoholic fatty liver disease in the majority. All had elevated serum creatine kinase. Genetic testing revealed a median of 46 CAG repeats. The phenotypes of our patients aligned with global data that is predominantly derived from participants of European ancestry.ConclusionWe describe a series of patients with KD from India with significant multisystemic involvement.}, } @article {pmid40324960, year = {2025}, author = {Simkins Lead, T and Shefner, JM and Kupfer, S and Malik, FI and Meng, L and Rudnicki, SA and Wei, J and van Eijk, RP}, title = {Application of the ENCALS predictive survival model in assessing the effect of the 24/44 inclusion criteria in FORTITUDE-ALS.}, journal = {Journal of neuromuscular diseases}, volume = {12}, number = {5}, pages = {679-682}, doi = {10.1177/22143602251336058}, pmid = {40324960}, issn = {2214-3602}, abstract = {FORTITUDE-ALS was a study evaluating reldesemtiv in people living with ALS. Post-hoc analysis identified larger treatment effects in those with symptom onset ≤24 months and baseline ALSFRS-R ≤ 44 (24/44 criteria). Using the ENCALS risk score (RS), we analyzed how the 24/44 criteria changed the eligible population. Of the 272 participants meeting the 24/44 criteria, 73% had very short to intermediate RS compared to 18% not meeting the criteria. Though the 24/44 criteria enriched the FORTITUDE-ALS population with rapidly progressing patients, they did not completely exclude all patients with a very long predicted survival.}, } @article {pmid40324158, year = {2025}, author = {Tabor Gray, L and Shune, S and Perry, S and Kosty, D and Namasivayam-MacDonald, A}, title = {Dysphagia Symptoms Contribute to Greater Care Partner Burden in Neurodegenerative Disease.}, journal = {American journal of speech-language pathology}, volume = {34}, number = {4}, pages = {2053-2061}, doi = {10.1044/2025_AJSLP-24-00529}, pmid = {40324158}, issn = {1558-9110}, mesh = {Aged ; Female ; Humans ; Male ; Middle Aged ; *Amyotrophic Lateral Sclerosis/psychology ; Canada ; *Caregiver Burden/psychology ; *Caregivers/psychology ; *Cost of Illness ; *Deglutition Disorders/psychology/etiology/diagnosis/physiopathology ; *Neurodegenerative Diseases/psychology/complications ; New Zealand ; *Parkinson Disease/psychology ; Severity of Illness Index ; United States ; }, abstract = {PURPOSE: Providing care for family members with neurodegenerative diseases entails significant physical and psychosocial costs, increasing caregiver burden. Limited research exists on the factors contributing to dysphagia-related burden, particularly across disease trajectories. This study aimed to (a) determine if dysphagia-related burden predicts general caregiver burden, (b) identify predictors of dysphagia-related burden, and (c) examine relationships between dysphagia severity, disease severity, and dysphagia-related burden.

METHOD: Care partners (N = 211; 80% female; Mage = 60 ± 14 years) from clinics in Canada, New Zealand, and the United States participated. Care recipients included those with amyotrophic lateral sclerosis (ALS; n = 48), dementia (n = 110), and Parkinson's disease (PD; n = 53). General burden was measured using the Zarit Burden Interview, while dysphagia-related burden was assessed via the Caregiver Assessment of Reported Experiences with Swallowing Difficulties. Multiple regression analyses examined predictors of general and dysphagia-related burden and their relationships to dysphagia and disease severity.

RESULTS: Higher general burden was associated with female caregivers (β = -.19, p = .05), higher education (β = .16, p = .03), caring for someone with dementia (β = .36, p = .01), and greater dysphagia-related burden (β = .33, p = .01). Predictors of dysphagia-related burden included working caregivers (β = .15, p = .01), increased dysphagia symptoms (β = .77, p < .01), and caring for individuals with ALS or dementia (vs. PD; β = -.16, p = .02). Dysphagia burden varied by disease severity and diet tolerance (p < .01).

CONCLUSIONS: Managing dysphagia independently contributes to caregiver burden, potentially increasing burnout and nonadherence to clinical recommendations. Early, proactive inquiry about dysphagia-related care partner burden and provision of support to minimize burden should be considered early in disease management.

SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.28843055.}, } @article {pmid40323286, year = {2025}, author = {Zhao, N and Jiang, J and Zhu, T and Wang, Z and Hu, W and Yin, F and Cao, H and Liao, M}, title = {First Report on Resistance to ALS-Inhibiting Herbicides in the Broadleaved Weed Common Vetch (Vicia sativa L.) and Visual Detection of the Associated ALS Resistance Mutation.}, journal = {Journal of agricultural and food chemistry}, volume = {73}, number = {19}, pages = {11606-11617}, doi = {10.1021/acs.jafc.5c01785}, pmid = {40323286}, issn = {1520-5118}, mesh = {*Herbicide Resistance ; *Herbicides/pharmacology ; *Acetolactate Synthase/genetics/antagonists & inhibitors/metabolism/chemistry ; *Plant Proteins/genetics/metabolism/chemistry/antagonists & inhibitors ; Mutation ; *Plant Weeds/drug effects/genetics/enzymology ; Molecular Docking Simulation ; *Enzyme Inhibitors/pharmacology ; China ; Arylsulfonates/pharmacology ; }, abstract = {Common vetch (Vicia sativa L.), an economically significant crop, is also a detrimental weed in wheat fields in the middle and lower reaches of the Yangtze River, China. A population of V. sativa (AHLQ-1) exhibiting high resistance (>10-fold) to ALS inhibitors, tribenuron-methyl and florasulam, was identified. All resistant plants carried a Pro-197-Ser substitution in their ALS genes, rendering their ALS enzymes 16.89 times less sensitive. Molecular docking revealed that the binding energies between ALS active sites and tribenuron-methyl or florasulam were reduced by over 80% due to the mutation at codon position 197. A LAMP method was successfully developed to visually detect this mutation, and a dCAPS assay was established to distinguish specific resistance mutations between homozygotes and heterozygotes. Additionally, cytochrome P450 activity was significantly elevated in resistant plants, enhancing the herbicide metabolism and resistance. This is the first global report of ALS resistance naturally occurring in V. sativa. These findings will aid in breeding herbicide-resistant V. sativa and improve resistance management.}, } @article {pmid40321778, year = {2025}, author = {Gao, G and Sumrall, ER and Walter, NG}, title = {Nanoscale domains govern local diffusion and aging within FUS condensates.}, journal = {Research square}, volume = {}, number = {}, pages = {}, pmid = {40321778}, issn = {2693-5015}, support = {R01 NS097542/NS/NINDS NIH HHS/United States ; R35 GM131922/GM/NIGMS NIH HHS/United States ; }, abstract = {Biomolecular condensates regulate cellular physiology by sequestering and processing RNAs and proteins, yet how these processes are locally tuned within condensates remains unclear. Moreover, in neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), condensates undergo liquid-to-solid phase transitions, but capturing early intermediates in this process has been challenging. Here, we present a surface multi-tethering approach to achieve intra-condensate single-molecule tracking of fluorescently labeled RNA and protein molecules within liquid-like condensates. Using RNA-binding protein Fused in Sarcoma (FUS) as a model for condensates implicated in ALS, we discover that RNA and protein diffusion is confined within distinct nanometer-scale domains, or nanodomains, which exhibit unique connectivity and chemical environments. During condensate aging, these nanodomains reposition, facilitating FUS fibrilization at the condensate surface, a transition enhanced by FDA-approved ALS drugs. Our findings demonstrate that nanodomain formation governs condensate function by modulating biomolecule sequestration and percolation, offering insights into condensate aging and disease-related transitions.}, } @article {pmid40321197, year = {2025}, author = {Rennels, CF and Rosow, L and Pantilat, S and Bell, BK and Lomen-Hoerth, C and Cohen, E and Bischoff, KE}, title = {Characteristics and Motivations of People With Amyotrophic Lateral Sclerosis Who Pursue Medical Aid in Dying in California.}, journal = {Neurology. Clinical practice}, volume = {15}, number = {3}, pages = {e200478}, pmid = {40321197}, issn = {2163-0402}, abstract = {BACKGROUND AND OBJECTIVES: People with amyotrophic lateral sclerosis (ALS) disproportionately pursue medical aid in dying (MAID). We described characteristics and motivations of patients with ALS who sought MAID in California.

METHODS: This is a retrospective cohort study of patients followed in the ALS and Palliative Care clinics at the University of California, San Francisco, between September 2017 and October 2023 who obtained a MAID prescription under California's End of Life Option Act. We abstracted demographic and clinical information from the electronic health record. We reviewed clinician notes to gather salient themes regarding patients' motivations for MAID and calculated the frequencies of motivations reported by prescribing physicians on standardized forms.

RESULTS: Thirty-seven patients obtained a MAID prescription. The median age at first documented inquiry about MAID was 64.0 years, 51.4% identified as women, 83.8% were White, and 10.8% had Medicaid. All spoke English and had a care partner. Most (70.3%) had limb-onset ALS. The median ALS Functional Rating Scale-Revised score was 28.5/48 and the median forced vital capacity was 41.5% at time of first inquiry about MAID. Most patients (70.3%) inquired about MAID during their first visit with palliative care. Physicians wrote MAID prescriptions at a median of 76 days after first inquiry. Most patients (73.0%) took MAID medications to end their lives, at a median of 39.5 days after the prescription was written.Clinician notes revealed that patients were commonly motivated to pursue MAID by concerns about current and future suffering, loss of autonomy and enjoyable activities, and desire for control at the end of life. On standardized forms completed after patients died, physicians documented that "persistent and uncontrollable pain and suffering" was a less common reason that patients pursued MAID.

DISCUSSION: Patients with ALS who requested MAID were largely White and English speaking. Most patients inquired about MAID when they had moderate-stage ALS and were early in their course of palliative care. Motivations for pursuing MAID often involved the accumulated losses characterizing ALS and worries about the future. Future studies should incorporate diverse patient voices, explore barriers to accessing MAID, and consider whether any interventions can ameliorate issues driving requests for MAID in people with ALS.}, } @article {pmid40320859, year = {2025}, author = {Watanabe, S and Yamanaka, K}, title = {Mitochondria and Endoplasmic Reticulum Contact Site as a Regulator of Proteostatic Stress Responses in Neurodegenerative Diseases.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {47}, number = {7}, pages = {e70016}, pmid = {40320859}, issn = {1521-1878}, support = {23K06826//Ministry of Education, Culture, Sports, Science and Technology, Japan/Japan Society for the Promotion of Science/ ; 19KK0214//Ministry of Education, Culture, Sports, Science and Technology, Japan/Japan Society for the Promotion of Science/ ; 22H00467//Ministry of Education, Culture, Sports, Science and Technology, Japan/Japan Society for the Promotion of Science/ ; JP22ek0109426//Japan Agency for Medical Research and Development/ ; JP24wm0425014//Japan Agency for Medical Research and Development/ ; JP24wm0625301//Japan Agency for Medical Research and Development/ ; //Takeda Science Foundation/ ; //Mochida Memorial Foundation for Medical and Pharmaceutical Research/ ; //Kowa Life Science Foundation/ ; //Novartis Foundation/ ; }, mesh = {Humans ; *Mitochondria/metabolism ; *Endoplasmic Reticulum/metabolism ; *Neurodegenerative Diseases/metabolism/pathology ; Animals ; *Proteostasis ; Calcium/metabolism ; Autophagy ; Amyotrophic Lateral Sclerosis/metabolism ; Mitochondrial Membranes/metabolism ; Alzheimer Disease/metabolism ; }, abstract = {Recent evidence indicates that the mitochondria-endoplasmic reticulum (ER) contact site is a novel microdomain essential for cellular homeostasis. Various proteins are accumulated at the mitochondria-associated membrane (MAM), an ER subcomponent closely associated with the mitochondria, contributing to Ca[2+] transfer to the mitochondria, lipid synthesis, mitochondrial fission/fusion, and autophagy. These functions are disrupted in the diseases, particularly in neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and Alzheimer's disease. In this review, we summarize the disruption of protein homeostasis in various neurodegenerative diseases, present recent works on the mechanisms of MAM aberration, including ours mainly focused on ALS, and then discuss challenges and prospects for future MAM-targeted therapies in neurodegenerative diseases.}, } @article {pmid40320052, year = {2025}, author = {Nadeem, A and Sharma, P and Gupta, P and Sandeep, P and Sharma, B and Sharma, N and Yadav, M and Dhiman, N}, title = {Exploring Neuregulin3: From physiology to pathology, a novel target for rational drug design.}, journal = {Biochemical pharmacology}, volume = {238}, number = {}, pages = {116964}, doi = {10.1016/j.bcp.2025.116964}, pmid = {40320052}, issn = {1873-2968}, mesh = {Humans ; Animals ; *Drug Design ; *Neuregulins/metabolism/genetics ; Neoplasms/drug therapy/metabolism/pathology ; *Drug Delivery Systems/methods/trends ; }, abstract = {Neuregulin 3 (NRG3) is an epidermal growth factor related protein that binds to and stimulates the Erb-B2 receptor tyrosine kinase 4 (ErbB4). NRG3 is a multifunctional protein with fifteen alternative splicing isoforms categorized into four classes. Numerous physiological processes, such as the formation of cortical plate, cortical patterning, synaptic development, neuronal proliferation, regulation of neurotransmission, control of impulsive behavior, mammary gland morphogenesis, spermatogonial proliferation and cardiac homeostasis are influenced by NRG3. Besides its physiological roles, NRG3 also modulates anxiogenic phenotypes. It is a susceptibility gene for schizophrenia, autism spectrum disorder and Hirschsprung's Disease. Furthermore, anxiety during nicotine withdrawal is dependent on NRG3-ErbB4 signaling. Research on a range of solid carcinomas, such as brain tumors, ovarian cancer, gastrointestinal cancer and breast cancer, has demonstrated NRG3 gene as a therapeutic target. NRG3 also has potential involvement in epilepsy, angular limb malformation in Rambouillet rams, amyotrophic lateral sclerosis and polythelia. Nevertheless, little is known about the molecular characteristics, activities specific to isoforms, and molecular mechanisms of NRG3. Examining its potential involvement in a range of physiological processes and pathological states is a unique area that needs in-depth study and may offer new mechanistic insights and comprehension of these elements. Thus, the purpose of this review is to shed light on the utility of NRG3 as a potential target in various health and disease conditions.}, } @article {pmid40319325, year = {2025}, author = {Mehdizadeh, S and Mamaghani, M and Hassanikia, S and Pilehvar, Y and Ertas, YN}, title = {Exosome-powered neuropharmaceutics: unlocking the blood-brain barrier for next-gen therapies.}, journal = {Journal of nanobiotechnology}, volume = {23}, number = {1}, pages = {329}, pmid = {40319325}, issn = {1477-3155}, mesh = {*Exosomes/metabolism/chemistry ; *Blood-Brain Barrier/metabolism/drug effects ; Humans ; Animals ; *Drug Delivery Systems/methods ; *Neuropharmacology/methods ; Drug Carriers/chemistry ; }, abstract = {BACKGROUND: The blood-brain barrier (BBB) presents a formidable challenge in neuropharmacology, limiting the delivery of therapeutic agents to the brain. Exosomes, nature's nanocarriers, have emerged as a promising solution due to their biocompatibility, low immunogenicity, and innate ability to traverse the BBB. A thorough examination of BBB anatomy and physiology reveals the complexities of neurological drug delivery and underscores the limitations of conventional methods.

MAIN BODY: This review explores the potential of exosome-powered neuropharmaceutics, highlighting their structural and functional properties, biogenesis, and mechanisms of release. Their intrinsic advantages in drug delivery, including enhanced stability and efficient cellular uptake, are discussed in detail. Exosomes naturally overcome BBB barriers through specific translocation mechanisms, making them a compelling vehicle for targeted brain therapies. Advances in engineering strategies, such as genetic and biochemical modifications, drug loading techniques, and specificity enhancement, further bolster their therapeutic potential. Exosome-based approaches hold immense promise for treating a spectrum of neurological disorders, including Alzheimer's, Parkinson's, amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), brain tumors, stroke, and psychiatric conditions.

CONCLUSION: By leveraging their innate properties and engineering innovations, exosomes offer a versatile platform for precision neurotherapeutics. Despite their promise, challenges remain in clinical translation, including large-scale production, standardization, and regulatory considerations. Future research directions in exosome nanobiotechnology aim to refine these therapeutic strategies, unlocking new avenues for treating neurological diseases. This review underscores the transformative impact of exosome-based drug delivery, paving the way for next-generation therapies that can effectively penetrate the BBB and revolutionize neuropharmacology.}, } @article {pmid40317507, year = {2025}, author = {Garret, MA and Namiranian, D and Milone, M and Varadhachary, A and Ho, D}, title = {Atypical Facial Onset Weakness in SOD1 ALS.}, journal = {Muscle & nerve}, volume = {72}, number = {3}, pages = {520-522}, doi = {10.1002/mus.28428}, pmid = {40317507}, issn = {1097-4598}, } @article {pmid40317297, year = {2025}, author = {Faltacco, V and Dalla Bella, E and Nigri, A and Telesca, A and Gandini, G and Riva, N and Vizziello, M and Medina, JP and Demichelis, G and Grisoli, M and Usai, S and Lauria, G and Consonni, M}, title = {Pathological laugher and crying in motor neuron diseases: a matter of bulbar and neurobehavioral involvement with sex imbalance.}, journal = {Journal of neurology}, volume = {272}, number = {5}, pages = {372}, pmid = {40317297}, issn = {1432-1459}, support = {2015-0023//Fondazione Regionale per la Ricerca Biomedica, Regione Lombardia/ ; 1157625//Fondo Europeo di Sviluppo Regionale, Regione Lombardia (POR FESR 2014-2020)/ ; }, mesh = {Humans ; Female ; Male ; *Crying/psychology/physiology ; Middle Aged ; *Motor Neuron Disease/physiopathology/psychology/diagnostic imaging/complications/pathology ; Aged ; *Laughter/physiology/psychology ; Magnetic Resonance Imaging ; *Affective Symptoms/etiology/physiopathology ; *Sex Characteristics ; Adult ; }, abstract = {BACKGROUND: Emotional lability (EL), also known as pathological laughter and crying, is a common but understudied symptom in motor neuron diseases (MND): amyotrophic lateral sclerosis and primary lateral sclerosis. This study aimed to investigate the prevalence of EL in MND and to explore the independent frequency components of laughter and crying in relation to motor, cognitive, neuropsychiatric, and neuroimaging factors.

METHODS: A total of 198 incident MND patients were enrolled. The Centre of Neurological Study-Lability Scale was used to measure EL. Associations between EL and motor function, mood, neuropsychological variables, and structural MRI were examined, with cortical thinning measured on a subset of 48 patients.

RESULTS: EL was identified in 36% of patients showing more severe motor functional disabilities, heightened depressive and anxiety symptoms and behavioral changes than those without EL. Women exhibited more severe EL and altered mood with frequent crying episodes than men. EL was strongly correlated with bulbar involvement. Crying episodes were associated with mood disorders, while laughter correlated with disinhibition and emotional regulation difficulties. EL had a specific association with the thinning of frontal regions, including the right pars orbitalis, which was also linked to altered emotional and behavioral regulation.

CONCLUSION: These findings underscore the role of corticobulbar and frontal pathways in EL pathophysiology. The study highlights the distinct mechanisms underlying pathological crying and laughter and their independency from general cognitive decline. It emphasizes the need for clinicians to recognize EL as an independent symptom, necessitating targeted management strategies to improve patient outcomes and support caregivers.}, } @article {pmid40316175, year = {2025}, author = {Iguchi, Y and Takahashi, Y and Li, J and Amakusa, Y and Kawakami, Y and Yoshimura, T and Chikuchi, R and Iida, M and Yokoi, S and Katsuno, M}, title = {Truncation mutation of CHMP2B disrupts late endosome function but reduces TDP-43 aggregation through HSP70 upregulation.}, journal = {Neurochemistry international}, volume = {187}, number = {}, pages = {105982}, doi = {10.1016/j.neuint.2025.105982}, pmid = {40316175}, issn = {1872-9754}, mesh = {Humans ; *Endosomes/metabolism/genetics ; *DNA-Binding Proteins/metabolism/genetics ; *HSP70 Heat-Shock Proteins/biosynthesis/genetics ; *Mutation/genetics ; Up-Regulation/physiology ; *Endosomal Sorting Complexes Required for Transport/genetics ; HEK293 Cells ; Frontotemporal Dementia/genetics ; Protein Aggregation, Pathological/genetics/metabolism ; }, abstract = {TAR DNA-binding protein 43 (TDP-43)-positive cytoplasmic aggregation is a pathological hallmark of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). This aggregation contributes substantially to the neurodegeneration of ALS and FTLD. The endosome, a key component of membrane trafficking in eukaryotic cells and is involved in the autophagy-lysosome pathway. Endosome-related genes such as CHMP2B, Alsin, and TMEM106B, are either causative or act as genetic modifiers in ALS and FTLD. However, the association between endosomal functions and TDP-43 aggregations remain poorly understood. The C-terminal truncation mutation CHMP2B, which causes frontotemporal dementia associated with chromosome 3 (FTD3), disrupts late endosome (LE)-lysosomes fusion. Nevertheless, FTD3 does not induce TDP-43 pathology. In this study, we showed that CHMP2B mutation-induced LE dysfunction promotes TDP-43 aggregate degradation through enhanced recruitment to juxtanuclear quality control compartments. Transcriptomic analysis revealed that CHMP2B[intron5] overexpression upregulates HSP70 expression. New insights into the connection between CMHP2B and HSP70 as well as the role of HSP70-mediated membrane trafficking in TDP-43 aggregation, offer a valuable understanding of the disease mechanism of ALS and FTLD.}, } @article {pmid40314791, year = {2025}, author = {Iuzzolino, VV and Scaravilli, A and Carignani, G and Senerchia, G and Pontillo, G and Dubbioso, R and Cocozza, S}, title = {Mapping motor and extra-motor gray and white matter changes in ALS: a comprehensive review of MRI insights.}, journal = {Neuroradiology}, volume = {}, number = {}, pages = {}, pmid = {40314791}, issn = {1432-1920}, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease primarily affecting motor neurons, yet with substantial clinical variability. Furthermore, beyond motor symptoms, ALS patients also show non-motor features, reflecting its classification as a multi-system disorder. The identification of reliable biomarkers is a critical challenge for improving diagnosis, tracking disease progression, and predicting patient outcomes. This review explores macro- and microstructural alterations in ALS, focusing on gray matter (GM) and white matter (WM) as observed through Magnetic Resonance Imaging (MRI). This approach synthesizes not only the expected involvement of motor areas but also highlights emerging evidence that these changes extend to extra-motor areas, such as the frontal and temporal lobes, underscoring the complex pathophysiology of ALS. The review emphasizes the potential of MRI as a non-invasive tool to provide new biomarkers by assessing both GM and WM integrity, a key advancement in ALS research. Additionally, it addresses existing discrepancies in findings and stresses the need for standardized imaging protocols. It also highlights the role of multi-modal MRI approaches in deepening our understanding of ALS pathology, emphasizing the importance of combining structural and diffusion MRI techniques to offer more comprehensive insights into ALS progression, ultimately advancing the potential for personalized treatment strategies and improving patient outcomes.}, } @article {pmid40313273, year = {2025}, author = {Dergai, O and Wuu, J and Koziczak-Holbro, M and Malaspina, A and Granit, V and Hernandez, JP and Cooley, A and Sachdev, R and Yu, L and Bidinosti, M and Flotte, L and Nash, M and Jennings, LL and Berry, JD and Bruijn, LI and Brachat, S and Benatar, M}, title = {Skeletal muscle biomarkers of amyotrophic lateral sclerosis: a large-scale, multi-cohort proteomic study.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, pmid = {40313273}, support = {/WT_/Wellcome Trust/United Kingdom ; U01 NS107027/NS/NINDS NIH HHS/United States ; U54 NS092091/NS/NINDS NIH HHS/United States ; }, abstract = {BACKGROUND: Biomarkers with clear contexts-of-use are important tools for ALS therapy development. Understanding their longitudinal trajectory in the untreated state is key to their use as potential markers of pharmacodynamic response. To this end, we undertook a large-scale proteomic study in well-phenotyped cohorts to identify biomarker candidates of ALS disease state and disease progression.

METHODS: Clinical phenotypic data and biofluid samples, collected from patients with ALS and healthy controls through multiple longitudinal natural history studies, were used to identify biomarker candidates. SOMAmer (Slow Off-rate Modified Aptamer)-based relatively quantitative measurement of ~7,000 proteins was performed in plasma and CSF, with immunoassay validation of candidates of interest.

RESULTS: We identified 329 plasma proteins significantly differentially regulated between ALS and controls (adjusted p-value <0.05), with 25 showing >40% relative abundance. PDLIM3, TNNT2, and MYL11 had the greatest log-fold elevation, while ANTXR2 and ART3 had the greatest log-fold reduction. A similar set of plasma proteins was found to increase (e.g. PDLIM3, TNNT2, MYL11) or decrease (e.g. ANTXR2, ART3, MSTN) with disease progression. CSF proteins with the greatest log-fold elevation included NEFL, NEFH, CHIT1, CA3, MYL11 and GPNMB. These results were confirmed in an independent replication cohort. Moreover, tissue-specific signature enrichment suggests a significant contribution of muscle as a source of these biomarkers. Immunoassays provided orthogonal validation of plasma TNNT2 and CSF GPNMB.

CONCLUSION: We identified an array of novel biomarkers with the potential to serve as response biomarkers to aid therapy development, as well as to shed light on the underlying biology of disease.}, } @article {pmid40312886, year = {2025}, author = {Spisto, M and Moretta, P and Senerchia, G and Iuzzolino, VV and Aruta, L and Salvatore, E and Santangelo, G and Trojano, L and Dubbioso, R}, title = {Identifying Mild Behavioral and Neurocognitive Impairment in Amyotrophic Lateral Sclerosis (MBNI-ALS) Provides Key Prognostic Insights.}, journal = {European journal of neurology}, volume = {32}, number = {5}, pages = {e70171}, pmid = {40312886}, issn = {1468-1331}, support = {E53D23019760001//PRIN-PNRR2022/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/complications/diagnosis/psychology ; Male ; Female ; *Cognitive Dysfunction/diagnosis/etiology ; Middle Aged ; Aged ; Prognosis ; Disease Progression ; Prospective Studies ; Neuropsychological Tests ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a multisystem neurodegenerative disease encompassing cognitive and behavioral impairments. The Revised Diagnostic Criteria for ALS-frontotemporal spectrum disorder (ALS-FTDS), while widely adopted, may overlook subtle impairments such as memory and visuospatial deficits, limiting their prognostic value.

OBJECTIVES: This study aimed to apply the Mild Behavioral and Neurocognitive Impairment (MBNI) approach, adapted from other neurodegenerative diseases, to ALS patients and assess its prognostic utility for survival and disease progression.

METHODS: A prospective cohort of 201 ALS patients was evaluated between January 2018 and July 2024. Participants underwent comprehensive cognitive and behavioral assessments. The MBNI approach identified patients with mild cognitive impairment (MCI), mild behavioral impairment (MBI), or combined cognitive-behavioral impairment (MCBI). Prognostic value was analyzed using Kaplan-Meier survival curves, Cox proportional hazards models, and logistic regression for disease progression.

RESULTS: Mild cognitive and/or behavioral impairments were detected in 67% of patients classified as cognitively normal by ALS-FTDS criteria. At a median follow-up of 15 months, these patients showed shorter tracheostomy-free survival (all p < 0.005). MCI (HR5.3; CI 1.10-25.41; p = 0.038) and frontotemporal dementia (HR6.2; Confidence Interval: 1.34-28.40; p = 0.019) independently predicted poor outcomes. Logistic regression confirmed that MCBI and frontotemporal dementia were associated with rapid progression (both p < 0.019).

CONCLUSION: The MBNI approach enhances the detection of mild cognitive and behavioral impairments in ALS, providing prognostic insights and improving stratification over the Revised Diagnostic Criteria for ALS-FTDS. This framework supports personalized care and the design of clinical trials targeting early disease stages.}, } @article {pmid40312429, year = {2025}, author = {Ludolph, AC and Grandjean, H and Reviers, E and De Micheli, V and Bianchi, C and Cardosi, L and Russ, H and Silani, V}, title = {Author Correction: The preferences of people with amyotrophic lateral sclerosis on riluzole treatment in Europe.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {15297}, doi = {10.1038/s41598-025-95009-7}, pmid = {40312429}, issn = {2045-2322}, } @article {pmid40311838, year = {2025}, author = {Recher, M and Canon, V and Lockhart-Bouron, M and Hubert, H and Javaudin, F and Leteurtre, S and Mitha, A and , }, title = {The peak end-tidal carbon dioxide concentration recorded during cardiopulmonary resuscitation as an indicator of survival: a nationwide cohort study of pediatric out-of-hospital cardiac arrests.}, journal = {Resuscitation}, volume = {212}, number = {}, pages = {110626}, doi = {10.1016/j.resuscitation.2025.110626}, pmid = {40311838}, issn = {1873-1570}, mesh = {Humans ; *Out-of-Hospital Cardiac Arrest/mortality/therapy/etiology ; *Cardiopulmonary Resuscitation/methods/mortality ; *Carbon Dioxide/analysis/metabolism ; Male ; Female ; Child ; Child, Preschool ; Infant ; Registries ; Adolescent ; Cohort Studies ; Tidal Volume ; France/epidemiology ; Return of Spontaneous Circulation ; ROC Curve ; }, abstract = {BACKGROUND: Although the end-tidal carbon dioxide concentration (ETCO2) recorded during resuscitation has been reported as an indicator of survival in a few studies of pediatric in-hospital cardiac arrest, the relationship between ETCO2 and survival in pediatric out-of-hospital cardiac arrest (OHCA) has not previously been investigated (particularly with regard to the cause of the OHCA). This study aimed to determine whether quantitative measurement of ETCO2 during resuscitation is predictive of survival in cases of pediatric OHCA.

METHOD: This nationwide, population-based cohort study analyzed data from the French RéAC OHCA registry, including all patients under 18 years of age with trauma-related OHCA or medical OHCA from 2011 to 2023. The highest ETCO2 value was recorded during advanced cardiopulmonary resuscitation. The main outcomes were return of spontaneous circulation (ROSC) and day (d)30 survival. Discriminant ability was evaluated using the area under the receiver operating characteristic curve (AUROC), and the Youden index was used to determine the optimal ETCO2 cut-off value.

RESULTS: A total of 1209 pediatric OHCAs (226 (19%) trauma-related and 983 (81%) medical) were included. The victims' median [interquartile range] age was 6 [0;14] years. ROSC was achieved in 347 (29%) cases and d30 survival was achieved in 61 (5%) cases. In both trauma-related and medical OHCAs, the peak recorded ETCO2 value was higher in patients who achieved ROSC and in d30 survivors. The AUROC [95% confidence interval] for the highest ETCO2 that predicted ROSC and d30 survival were respectively 0.808 [0.745-0.872] and 0.854 [0.761-0.947] for the trauma-related OHCA group and 0.803 [0.774-0.831] and 0.732 [0.676-0.787] for the medical OHCA group. In both groups, the probability of ROSC and d30 survival increased with higher ETCO2 values, with optimal cut-offs of 21 and 29 mmHg for trauma-related OHCA and 27 and 26 mmHg for medical OHCA, respectively.

CONCLUSIONS: Further studies are necessary to clarify the use of ETCO2 in optimizing pediatric ALS.}, } @article {pmid40311553, year = {2025}, author = {Dulski, J and Pant, DC and Hoffman-Zacharska, D and Kwaśniak-Butowska, M and Wszolek, ZK and Sławek, J}, title = {KIF5A variant in familial dystonia: A clinicogenetic study of a large Roma kindred.}, journal = {Parkinsonism & related disorders}, volume = {135}, number = {}, pages = {107825}, doi = {10.1016/j.parkreldis.2025.107825}, pmid = {40311553}, issn = {1873-5126}, mesh = {Humans ; *Kinesins/genetics ; Male ; Female ; Pedigree ; Adult ; Middle Aged ; *Dystonic Disorders/genetics ; Mutation, Missense ; Young Adult ; }, abstract = {BACKGROUND: Mutations in the KIF5A gene were associated with several neurological diseases, including hereditary spastic paraplegia type 10, Charcot-Marie-Tooth type 2, amyotrophic lateral sclerosis, and neonatal intractable myoclonus. To date, none of the KIF5A variants was linked with dystonia. This study presents the first family with autosomal-dominant dystonia exhibiting incomplete penetrance, potentially linked to a KIF5A variant.

METHODS: Seven family members were recruited between 2017 and 2024. Detailed medical history and neurological examination were conducted for all. Genetic screening, including Sanger sequencing, MLPA analysis of SGCE, and PCR RFLP/BseRI for the common dystonia TOR1A mutation (c.907-909del), followed by whole exome sequencing, was performed on the proband and one affected relative. The genetic status of the remaining five individuals was assessed with Sanger sequencing.

RESULTS: A missense variant in the KIF5A c.118G > A was found in four affected and one asymptomatic individual, while it was absent in two non-affected individuals. The variant is rare in the general population (0.00001 in gnomAD 4.0), affects a highly conserved amino acid, and in silico models (M-CAP) indicates it is pathogenic. It was classified as likely pathogenic per ACMG criteria (PM1, PM2, PP2, PP3).

CONCLUSIONS: Our study suggests that KIF5A could represent a potential dystonia gene and sheds light on the broader role of motor proteins in human health and disease. This further expands the phenotypes associated with KIF5A and highlights the importance for clinicians to include this variant in their screening panels, as it tends to be underrepresented in current databases.}, } @article {pmid40311013, year = {2025}, author = {Xu, Z and Yi, W and Guan, L and Tang, J and Feng, D and Zou, Y}, title = {Deciphering the Inhibitory Mechanism of ALS-Associated N352S and S352p Variants against TDP-43 Aggregation and Its Destabilization Effect on TDP-43 Protofibrils.}, journal = {ACS chemical neuroscience}, volume = {16}, number = {10}, pages = {1898-1908}, doi = {10.1021/acschemneuro.5c00045}, pmid = {40311013}, issn = {1948-7193}, mesh = {*Amyotrophic Lateral Sclerosis/genetics/metabolism ; *DNA-Binding Proteins/genetics/metabolism/chemistry ; Humans ; Molecular Dynamics Simulation ; Phosphorylation ; Mutation/genetics ; Protein Aggregates/genetics ; *Protein Aggregation, Pathological/genetics/metabolism ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is closely related to ubiquitin-positive inclusions formed by transactive response deoxyribonucleic acid (DNA) binding protein of 43 kDa (TDP-43). Previous experiments identified that the ALS-linked familial variant, N352S (asparagine substituted by serine), and subsequent phosphorylation of S352 (S352p) are associated with the aggregation of TDP-43. However, the underlying molecular mechanisms are still not fully understood. By performing all-atom explicit-solvent replica exchange molecular dynamics (REMD) simulations with a total simulation time of 100.8 μs, we scrutinized the impact of the N352S mutation and its phosphorylation variant S352p on the conformational ensembles of the TDP-43342-366 dimer. Our simulation results show that both the N352S and S352p variants could promote the formation of unstructured conformation and impede the formation of β-structure and helix content, and the inhibitive effect of S352P is more obvious. Further analyses suggest that the H-bonding and hydrophobic interaction among TDP-43342-366 peptides, as well as the R361-E362 salt bridge, are attenuated by N352S and S352p variants. Additional MD simulations show that N352S and S352p variants reduce the structural stability of the hydrophobic region and lower the number of H-bonds and contacts of two hydrophobic clusters, thus possessing a destabilization effect on the TDP-43282-360 protofibrils. Our results unmask the molecular mechanism of the N352S mutation and its phosphorylation variant S352p toward the inhibition of TDP-43342-366 aggregation and prove the protofibril-destabilizing effects of these two variants, which may be helpful for designing drugs for the treatment of ALS.}, } @article {pmid40310505, year = {2025}, author = {Gautam, P and Yadav, R and Vishwakarma, RK and Pathak, A and Singh, C}, title = {Metabolic dysregulation in amyotrophic lateral sclerosis: insights from [1]H NMR-based metabolomics in a tertiary care center in India.}, journal = {Metabolic brain disease}, volume = {40}, number = {5}, pages = {196}, pmid = {40310505}, issn = {1573-7365}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism/blood ; *Metabolomics/methods ; Male ; Female ; India ; Middle Aged ; Case-Control Studies ; Adult ; Tertiary Care Centers ; Biomarkers/blood/metabolism ; Aged ; Pilot Projects ; Proton Magnetic Resonance Spectroscopy/methods ; Magnetic Resonance Spectroscopy/methods ; }, abstract = {Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disorder characterized by motor neuron loss, leading to severe physical impairment and mortality. Despite available treatments like Riluzole and Edaravone, their limited efficacy highlights the need for improved understanding of ALS pathology. This study has explored metabolic alterations in North Indian ALS patients using [1]H Nuclear Magnetic Resonance (NMR)-based metabolomics. A case-control study, involving 45 ALS patients and 30 healthy controls (HCs) was performed. Serum samples were analyzed using 600-MHz NMR spectrometer, revealing significant metabolic differences between ALS and HC groups. Multivariate analyses identified nine dysregulated metabolites-pyruvate, glutamine, histidine, isoleucine, leucine, imidazole, arginine, creatinine, and choline-with ROC analysis showing isoleucine as a promising biomarker (AUC 83%). Pathway enrichment analysis highlighted disruptions in key metabolic pathways, including the Glucose-Alanine Cycle, Urea Cycle, Ammonia Recycling, and the Warburg Effect, suggesting potential links to neuroinflammatory and mitochondrial dysfunction in ALS pathogenesis. This pilot study provides insight into ALS-specific metabolic alterations in Indian cohort and demonstrates the potential of these metabolites as diagnostic biomarkers. Our findings identify potential biomarkers that require validation in larger, multi-centric cohorts to support diagnosis, prognosis, and improved management of ALS.}, } @article {pmid40310478, year = {2025}, author = {de Moura-Silva, IA and Rodrigues, BJS and Posso, DA and Bacarin, MA and Borella, J}, title = {Growth inhibition of Pontederia crassipes to imidazolinones herbicides-group exposure.}, journal = {Ecotoxicology (London, England)}, volume = {34}, number = {6}, pages = {958-972}, pmid = {40310478}, issn = {1573-3017}, support = {001//Coordenação de Aperfeiçoamento de Pessoal de Nível Superior/ ; 21/2551-0000621-8//Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul/ ; }, mesh = {*Herbicides/toxicity ; *Water Pollutants, Chemical/toxicity ; *Nicotinic Acids/toxicity ; *Imidazoles/toxicity ; Plant Leaves/drug effects ; Oxidative Stress ; Niacin/analogs & derivatives ; }, abstract = {ALS-inhibiting imidazolinone herbicides are widely used for selective weed control in Clearfield[®] cropping systems. However, their physicochemical properties promote dispersion into adjacent aquatic environments, posing risks to non-target organisms such as aquatic macrophytes. This study aimed to elucidate the toxicological effects of the commercial formulation Kifix[®] (a mixture of imazapyr and imazapic) on Pontederia crassipes, with emphasis on its biochemical and physiological responses. Two experiments were conducted using herbicide concentrations ranging from 0.2-1.0 mg L[-1], alongside untreated controls. Multiple parameters were evaluated in leaves and roots at 7 and 14 days after application, including visual symptoms, chlorophyll index, growth parameters, chlorophyll a fluorescence, gas exchange, epidermal anatomy, reactive oxygen species, lipid peroxidation, electrolyte leakage, antioxidant enzyme activity, glycolate oxidase, glutathione S-transferase, and acetolactate synthase activity, as well as carbohydrate, amino acid, and protein content. Upon exposure, mature leaves exhibited photochemical impairment, compromising carbon assimilation and photorespiration, and leading to carbohydrate accumulation. Stomatal aperture and conductance were also negatively affected. Oxidative stress responses and antioxidant enzyme activity changed in both leaves and roots. Notably, acetolactate synthase activity increased in treated plants, while protein and amino acid contents remained unchanged. Overall, Kifix[®] significantly impaired P. crassipes, particularly by inhibiting the development of new tissues-such as leaves and plantlets essential for reproduction and spread-while also triggering physiological and biochemical disturbances in mature tissues.}, } @article {pmid40310263, year = {2025}, author = {Alidoost, M and Huang, JY and Dermentzaki, G and Blazier, AS and Gaglia, G and Hammond, TR and Frau, F and McCorry, MC and Ofengeim, D and Wilson, JL}, title = {Uncovering New Therapeutic Targets for Amyotrophic Lateral Sclerosis and Neurological Diseases Using Real-World Data.}, journal = {Clinical pharmacology and therapeutics}, volume = {118}, number = {1}, pages = {242-251}, pmid = {40310263}, issn = {1532-6535}, support = {//Sanofi iDEA-TECH/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/drug therapy/mortality ; Humans ; *Drug Repositioning/methods ; *Nervous System Diseases/drug therapy ; Retrospective Studies ; Molecular Targeted Therapy ; Electronic Health Records ; Complement System Proteins/metabolism ; }, abstract = {Although attractive for relevance to real-world scenarios, real-world data (RWD) is typically used for drug repurposing and not therapeutic target discovery. Repurposing studies have identified few effective options in neurological diseases such as the rare disease, amyotrophic lateral sclerosis (ALS), which has no disease-modifying treatments available. We previously reclassified drugs by their simulated effects on proteins downstream of drug targets and observed class-level effects in the EHR, implicating the downstream protein as the source of the effect. Here, we developed a novel ALS-focused network medicine model using data from patient samples, the public domain, and consortia. With this model, we simulated drug effects on ALS and measured class effects on overall survival in retrospective EHR studies. We observed an increased but non-significant risk of death for patients taking drugs with complement system proteins downstream of their targets and experimentally validated drug effects on complement activation. We repeated this for six protein classes, three of which, including multiple chemokine receptors, were associated with a significantly increased risk for death, suggesting that targeting proteins such as CXCR5, CXCR3, chemokine signaling generally, or neuropeptide Y (NPY) could be advantageous therapeutic targets for these patients. We expanded our analysis to the neuroinflammatory condition, myasthenia gravis, and neurodegenerative disease, Parkinson's, and recovered similar effect sizes. We demonstrated the utility of network medicine for testing novel therapeutic effects using RWD and believe this approach may accelerate target discovery in neurological diseases, addressing the critical need for new therapeutic options.}, } @article {pmid40309800, year = {2025}, author = {Manai, AL and Caria, P and Noli, B and Contini, C and Manconi, B and Etzi, F and Cocco, C}, title = {VGF and Its Derived Peptides in Amyotrophic Lateral Sclerosis.}, journal = {Brain sciences}, volume = {15}, number = {4}, pages = {}, pmid = {40309800}, issn = {2076-3425}, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by a progressive degeneration in the neurons of the frontal cortex, spinal cord, and brainstem, altering the correct release of neurotransmitters. The disease affects every muscle in the body and could cause death three to five years after symptoms first occur. There is currently no efficient treatment to stop the disease's progression. The lack of identification of potential therapeutic strategies is a consequence of the delayed diagnosis due to the absence of accurate ALS early biomarkers. Indeed, neurotransmitters altered in ALS are not measurable in body fluids at quantities that allow for testing, making their use as diagnostic tools a challenge. Contrarily, neuroproteins and neuropeptides are chemical messengers produced and released by neurons, and most of them have the potential to enter bodily fluids. To find out new possible ALS biomarkers, the research of neuropeptides and proteins is intensified using mass spectrometry and biochemical-based assays. Neuropeptides derived from the proVGF precursor protein act as signaling molecules within neurons. ProVGF and its derived peptides are expressed in the nervous and endocrine systems but are also widely distributed in body fluids such as blood, urine, and cerebrospinal fluid, making them viable options as disease biomarkers. To highlight the proVGF and its derived peptides' major roles as ALS diagnostic biomarkers, this review provides an overview of the VGF peptide alterations in spinal cord and body fluids and outlines the limitations of the reported investigations.}, } @article {pmid40309798, year = {2025}, author = {de Carvalho, M}, title = {Developments in Neurodegenerative Disorders: Highly Cited Articles Published in Brain Sciences in 2023-2024.}, journal = {Brain sciences}, volume = {15}, number = {4}, pages = {}, pmid = {40309798}, issn = {2076-3425}, abstract = {Neurodegenerative disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS), pose a significant and growing health concern, particularly in developed countries [...].}, } @article {pmid40309789, year = {2025}, author = {Khan, S and Kallis, L and Mee, H and El Hadwe, S and Barone, D and Hutchinson, P and Kolias, A}, title = {Invasive Brain-Computer Interface for Communication: A Scoping Review.}, journal = {Brain sciences}, volume = {15}, number = {4}, pages = {}, pmid = {40309789}, issn = {2076-3425}, abstract = {BACKGROUND: The rapid expansion of the brain-computer interface for patients with neurological deficits has garnered significant interest, and for patients, it provides an additional route where conventional rehabilitation has its limits. This has particularly been the case for patients who lose the ability to communicate. Circumventing neural injuries by recording from the intact cortex and subcortex has the potential to allow patients to communicate and restore self-expression. Discoveries over the last 10-15 years have been possible through advancements in technology, neuroscience, and computing. By examining studies involving intracranial brain-computer interfaces that aim to restore communication, we aimed to explore the advances made and explore where the technology is heading.

METHODS: For this scoping review, we systematically searched PubMed and OVID Embase. After processing the articles, the search yielded 41 articles that we included in this review.

RESULTS: The articles predominantly assessed patients who had either suffered from amyotrophic lateral sclerosis, cervical cord injury, or brainstem stroke, resulting in tetraplegia and, in some cases, difficulty speaking. Of the intracranial implants, ten had ALS, six had brainstem stroke, and thirteen had a spinal cord injury. Stereoelectroencephalography was also used, but the results, whilst promising, are still in their infancy. Studies involving patients who were moving cursors on a screen could improve the speed of movement by optimising the interface and utilising better decoding methods. In recent years, intracortical devices have been successfully used for accurate speech-to-text and speech-to-audio decoding in patients who are unable to speak.

CONCLUSIONS: Here, we summarise the progress made by BCIs used for communication. Speech decoding directly from the cortex can provide a novel therapeutic method to restore full, embodied communication to patients suffering from tetraplegia who otherwise cannot communicate.}, } @article {pmid40309514, year = {2025}, author = {Li, V and Huang, Y}, title = {Oligonucleotide therapeutics for neurodegenerative diseases.}, journal = {NeuroImmune pharmacology and therapeutics}, volume = {4}, number = {1}, pages = {1-11}, pmid = {40309514}, issn = {2750-6665}, support = {R44 DC018463/DC/NIDCD NIH HHS/United States ; R44 DC018762/DC/NIDCD NIH HHS/United States ; }, abstract = {Recently there has been a surge in interest involving the application of oligonucleotides, including small interfering RNA (siRNA) and antisense oligonucleotides (ASOs), for the treatment of chronic diseases that have few available therapeutic options. This emerging class of drugs primarily operates by selectively suppressing target genes through antisense and/or RNA interference mechanisms. While various commercial medications exist for delivering oligonucleotides to the hepatic tissue, achieving effective delivery to extra hepatic tissues remains a formidable challenge. Here, we review recent advances in oligonucleotide technologies, including nanoparticle delivery, local administration, and 2'-O-hexadecyl (C16)-conjugation that work to extend the applicability of siRNAs and ASOs to nerve tissues. We discuss critical factors pivotal for the successful clinical translations of these modified or engineered oligonucleotides in the context of treating neurodegenerative diseases such as Alzheimer's disease and amyotrophic lateral sclerosis.}, } @article {pmid40309037, year = {2025}, author = {Yu, Q and Mohammed Nazar, RB and Chen, S and Qian, Q and Wang, J and Chen, X}, title = {A novel SIGMAR1 missense mutation leads to distal hereditary motor neuropathy phenotype mimicking juvenile ALS: a case report of China.}, journal = {Frontiers in genetics}, volume = {16}, number = {}, pages = {1477518}, pmid = {40309037}, issn = {1664-8021}, abstract = {We present the case of a 16-year-old East Asian Chinese girl with a novel mutation in the SIGMAR1 gene, initially diagnosed as juvenile amyotrophic lateral sclerosis (JALS). At the age of five, she began to exhibit gait abnormalities while walking, a condition that persisted for 4 years until muscle weakness and atrophy emerged, predominantly affecting her distal muscles symmetrically. Electromyography (EMG) initially revealed early abonormal motor conduction, and subsequent examinations indicated neurogenic damage accompanied by localized denervation potentials. Whole-exome sequencing identified compound heterozygous mutations in the SIGMAR1 gene. Throughout the course of her illness, the patient exhibited slow disease progression without cognitive impairment or scoliosis development. We ultimately revised the diagnosis to distal hereditary motor neuropathy (dHMN). This study reports the case of SIGMAR1 new locus mutation leading to dHMN in China, contributing to the expansion of the dHMN genetic database. In our patient, the initial EMG findings indicated issues with neurogenic conduction, followed by a slow progression of the disease. Subsequently, EMG results revealed axonal damage and denervation potentials. These clinical features can easily lead to confusion with JALS. This insight is valuable for improving diagnostic accuracy and understanding the clinical spectrum of dHMN related to SIGMAR1 mutations.}, } @article {pmid40307231, year = {2025}, author = {Yen, YP and Lung, TH and Liau, ES and Wu, CC and Huang, GL and Hsu, FY and Chang, M and Yang, ZD and Huang, CY and Zheng, Z and Zhao, W and Hung, JH and He, C and Nie, Q and Chen, JA}, title = {The motor neuron m6A repertoire governs neuronal homeostasis and FTO inhibition mitigates ALS symptom manifestation.}, journal = {Nature communications}, volume = {16}, number = {1}, pages = {4063}, pmid = {40307231}, issn = {2041-1723}, support = {NHRI-EX113-11330NI//National Health Research Institutes (NHRI)/ ; AS-GCP-113-L02//Academia Sinica/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology ; Animals ; *Motor Neurons/metabolism/pathology ; *Methyltransferases/metabolism/genetics ; Humans ; Induced Pluripotent Stem Cells/metabolism ; Mice ; *Adenosine/analogs & derivatives/metabolism ; *Alpha-Ketoglutarate-Dependent Dioxygenase FTO/metabolism/antagonists & inhibitors/genetics ; Homeostasis ; Disease Models, Animal ; Mice, Knockout ; Male ; Methylation ; Female ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a swiftly progressive and fatal neurodegenerative ailment marked by the degenerative motor neurons (MNs). Why MNs are specifically susceptible in predominantly sporadic cases remains enigmatic. Here, we demonstrated N[6]-methyladenosine (m[6]A), an RNA modification catalyzed by the METTL3/METTL14 methyltransferase complex, as a pivotal contributor to ALS pathogenesis. By conditional knockout Mettl14 in murine MNs, we recapitulate almost the full spectrum of ALS disease characteristics. Mechanistically, pervasive m[6]A hypomethylation triggers dysregulated expression of high-risk genes associated with ALS and an unforeseen reduction of chromatin accessibility in MNs. Additionally, we observed diminished m[6]A levels in induced pluripotent stem cell derived MNs (iPSC~MNs) from familial and sporadic ALS patients. Restoring m[6]A equilibrium via a small molecule or gene therapy significantly preserves MNs from degeneration and mitigates motor impairments in ALS iPSC~MNs and murine models. Our study presents a substantial stride towards identifying pioneering efficacious ALS therapies via RNA modifications.}, } @article {pmid40306441, year = {2025}, author = {Chen, Y and Sun, S and Gao, N and Bai, Z and Yu, W and Zhao, B and Yun, Y and Sun, X and Lin, P and Li, W and Zhao, Y and Yan, C and Liu, S}, title = {Proximity extension assay reveals serum inflammatory biomarkers in two amyotrophic lateral sclerosis cohorts.}, journal = {Neurobiology of disease}, volume = {211}, number = {}, pages = {106933}, doi = {10.1016/j.nbd.2025.106933}, pmid = {40306441}, issn = {1095-953X}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/blood/diagnosis/genetics ; Biomarkers/blood ; Male ; Female ; Middle Aged ; Cohort Studies ; Aged ; *Inflammation/blood ; Adult ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a rare neurodegenerative disease with both clinical and hereditary heterogeneity. Inflammation has been suggested to play an important role in ALS pathophysiology. In this study, we aimed to identify serum inflammatory alterations and develop effective inflammatory biomarkers to assist in the diagnosis of ALS. Through proximity extension assay (PEA), we investigated serum inflammatory alterations in two ALS cohorts compared with healthy controls (HCs), including sporadic ALS patients and genetic ALS patients. We found that CHIT1, OSM, SIRT2, CDCP1 and 5 other factors were significantly increased in sporadic ALS patients in both cohorts and that SIRT2, CDCP1 and 6 other factors were different between genetic ALS patients and HCs. Using XGBoost and binary logistic regression analysis, we developed a two-serum protein diagnostic panel (CHIT1 and CDCP1), and the area under the curve (AUC) was 0.904 in the original cohort and 0.907 in the replication cohort. Based on Mendelian Randomization (MR), OSM and SIRT2 are significantly associated with the risk of ALS. In conclusion, our study revealed a consistent and replicable serum inflammatory profile and developed a biomarker panel that can differentiate ALS patients from HCs in two cohorts, which may play an important role in advancing our current understanding of the inflammatory process and identifying novel therapeutic strategies for ALS patients.}, } @article {pmid40306255, year = {2025}, author = {Bu, Y and Yuan, Y and Hu, F and Zhao, Q and He, C and Tang, L and Li, Y and Liu, Z and Weng, L and Du, J and Guo, J and Shen, L and Li, J and Yi, J and Cao, W and Xu, R and Tang, B and Wang, J}, title = {Retinal alterations induced by amyotrophic lateral sclerosis: An analysis using optical coherence tomography.}, journal = {Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia}, volume = {136}, number = {}, pages = {111268}, doi = {10.1016/j.jocn.2025.111268}, pmid = {40306255}, issn = {1532-2653}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnostic imaging/complications/pathology ; *Tomography, Optical Coherence/methods ; Male ; Female ; Middle Aged ; Cross-Sectional Studies ; *Retina/diagnostic imaging/pathology ; Aged ; Adult ; Disease Progression ; Nerve Fibers/pathology ; }, abstract = {OBJECTIVE: In this study, we aimed to investigate retinal changes in a large cohort of amyotrophic lateral sclerosis (ALS) patients and healthy controls (HCs) to further elucidate their relationship with ALS.

METHODS: This was a cross-sectional observational study. We evaluated retinal layer thickness in 134 ALS patients and 66 HCs using optical coherence tomography (OCT). Particularly, we focused on the macular region and peripapillary retinal nerve fiber layer (p-RNFL).

RESULTS: The examination of retinal layers in ALS patients revealed a significant change in the inner nuclear layer (INL), with a pattern of initial thickening followed by thinning, which correlated with disease stages, most notably in the inner nasal quadrant. Moreover, the p-RNFL in the temporal quadrant was thinner in ALS patients compared to HCs. In addition, ALS patients who developed bulbar symptoms exhibited marginally thinner p-RNFL in the temporal quadrant compared to those without bulbar symptoms. Interestingly, a thinner p-RNFL in the temporal quadrant did not correlate with faster disease progression.

CONCLUSION: This study reveals notable changes in the INL and p-RNFL thickness in ALS patients, highlighting the intricate relationship between retinal changes and ALS progression. Despite these retinal alterations, no correlation with disease progression rate was observed. These findings suggest that while OCT shows potential in monitoring ALS, its role in predicting disease course requires further investigation with long-term longitudinal studies and diverse patient cohorts.}, } @article {pmid40305762, year = {2025}, author = {Manohar, R and Yang, FX and Stephen, CD and Schmahmann, JD and Eklund, NM and Gupta, AS}, title = {At-home wearables and machine learning capture motor impairment and progression in adult ataxias.}, journal = {Brain : a journal of neurology}, volume = {}, number = {}, pages = {}, doi = {10.1093/brain/awaf154}, pmid = {40305762}, issn = {1460-2156}, support = {R01 NS117826/NS/NINDS NIH HHS/United States ; R01 NS134597/NS/NINDS NIH HHS/United States ; }, abstract = {A significant barrier to developing disease-modifying therapies for spinocerebellar ataxias (SCAs) and multiple system atrophy of the cerebellar type (MSA-C) is the scarcity of tools to sensitively measure disease progression in clinical trials. Wearable sensors worn continuously during natural behavior at home have the potential to produce ecologically valid and precise measures of motor function by leveraging frequent and numerous high-resolution samples of behavior. Here we test whether movement-building block characteristics (i.e., submovements), obtained from the wrist and ankle during natural behavior at home, can sensitively capture disease progression in SCAs and MSA-C, as recently shown in amyotrophic lateral sclerosis (ALS) and ataxia telangiectasia (A-T). Remotely collected cross-sectional (n = 76) and longitudinal data (n = 27) were analyzed from individuals with ataxia (SCAs 1, 2, 3, and 6, MSA-C) and controls. Machine learning models were trained to produce composite outcome measures based on submovement properties. Two models were trained on data from individuals with ataxia to estimate ataxia rating scale scores. Two additional models, previously trained entirely on longitudinal ALS data to optimize sensitivity to change, were also evaluated. All composite outcomes from both wrist and ankle sensor data had moderate to strong correlations with ataxia rating scales and self-reported function, showed differences between ataxia and control groups with high effect size, and had high within-week reliability. The composite outcomes trained on longitudinal ALS data most strongly captured disease progression over time. These data demonstrate that outcome measures based on accelerometers worn at home can accurately capture the ataxia phenotype and sensitively measure disease progression. This assessment approach is scalable and can be used in clinical or research settings with relatively low individual burden.}, } @article {pmid40305176, year = {2025}, author = {Erichsen, PA and Henriksen, EE and Nielsen, JE and Ejlerskov, P and Simonsen, AH and Toft, A}, title = {Immunological Fluid Biomarkers in Frontotemporal Dementia: A Systematic Review.}, journal = {Biomolecules}, volume = {15}, number = {4}, pages = {}, pmid = {40305176}, issn = {2218-273X}, support = {0084960//Novo Nordisk Foundation/ ; R450-2023-989//Lundbeck Foundation/ ; }, mesh = {Humans ; *Frontotemporal Dementia/immunology/blood/cerebrospinal fluid ; *Biomarkers/cerebrospinal fluid/blood ; Alzheimer Disease/immunology/blood/cerebrospinal fluid ; Amyotrophic Lateral Sclerosis/blood/immunology/cerebrospinal fluid ; Chitinase-3-Like Protein 1/cerebrospinal fluid/blood ; Glial Fibrillary Acidic Protein/cerebrospinal fluid/blood ; Chemokine CCL2/cerebrospinal fluid/blood ; }, abstract = {Dysregulated immune activation plays a key role in the pathogenesis of neurodegenerative diseases, including frontotemporal dementia (FTD). This study reviews immunological biomarkers associated with FTD and its subtypes. A systematic search of PubMed and Web of Science was conducted for studies published before 1 January 2025, focusing on immunological biomarkers in CSF or blood from FTD patients with comparisons to healthy or neurological controls. A total of 124 studies were included, involving 6686 FTD patients and 202 immune biomarkers. Key findings include elevated levels of GFAP and MCP1/CCL2 in both CSF and blood and consistently increased CHIT1 and YKL-40 in CSF. Complement proteins from the classical activation pathway emerged as promising targets. Distinct immune markers were found to differentiate FTD from Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS), with GFAP, SPARC, and SPP1 varying between FTD and AD and IL-15, HERV-K, NOD2, and CHIT1 differing between FTD and ALS. A few markers, such as Galectin-3 and PGRN, distinguished FTD subtypes. Enrichment analysis highlighted IL-10 signaling and immune cell chemotaxis as potential pathways for further exploration. This study provides an overview of immunological biomarkers in FTD, emphasizing those most relevant for future research on immune dysregulation in FTD pathogenesis.}, } @article {pmid40304918, year = {2025}, author = {Anjum, F and Alsharif, A and Bakhuraysah, M and Shafie, A and Hassan, MI and Mohammad, T}, title = {Discovering Novel Biomarkers and Potential Therapeutic Targets of Amyotrophic Lateral Sclerosis Through Integrated Machine Learning and Gene Expression Profiling.}, journal = {Journal of molecular neuroscience : MN}, volume = {75}, number = {2}, pages = {61}, pmid = {40304918}, issn = {1559-1166}, support = {KSRG-2024-446//King Salman Center for Disability Research/ ; KSRG-2024-446//King Salman Center for Disability Research/ ; KSRG-2024-446//King Salman Center for Disability Research/ ; KSRG-2024-446//King Salman Center for Disability Research/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/genetics/metabolism ; Humans ; *Machine Learning ; Receptors, Nicotinic/genetics/metabolism ; Gene Expression Profiling ; Biomarkers/metabolism ; Tumor Suppressor Proteins/genetics/metabolism ; Transcriptome ; Membrane Proteins/genetics/metabolism ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder that has multiple factors that make its molecular pathogenesis difficult to understand and its diagnosis and treatment during the early stages difficult to determine. Discovering novel biomarkers in ALS for diagnostic and therapeutic potential has become important. Consequently, bioinformatics and machine learning algorithms are useful for identifying differentially expressed genes (DEGs) and potential biomarkers, as well as understanding the molecular mechanisms and intricacies of diseases such as ALS. To achieve the aim of the present study, six datasets obtained from the Gene Expression Omnibus (GEO) were utilized and analyzed using an integrative bioinformatics and machine learning approach. Log transformation was done during data preprocessing, RMA normalization was performed, and the batch effect was corrected. Differential expression analysis identified 206 DEGs that were significantly associated with different biological processes, including muscle function, energy metabolism, and mitochondrial membrane activity. Functional enrichment analysis highlighted pathways, including those related to prion disease, Parkinson's disease, and ATP synthesis via chemiosmotic coupling. We employed a multi-step machine learning framework incorporating random forest, LASSO regression, and SVM-RFE to identify robust biomarkers. This approach identified three key genes, CHRNA1, DLG5, and PLA2G4C, which could be explored as promising biomarkers for ALS after further validation. The internal validation, including principal component analysis (PCA) and ROC-AUC analysis, demonstrated strong diagnostic potential of these hub genes, achieving an AUC of 0.96. This work highlights the utility of bioinformatics and machine learning in identifying key genes as biomarkers for diagnostic and therapeutic potential in ALS.}, } @article {pmid40304712, year = {2025}, author = {Freisem, D and Hoenigsperger, H and Catanese, A and Sparrer, KMJ}, title = {Inborn errors of canonical autophagy in neurodegenerative diseases.}, journal = {Human molecular genetics}, volume = {}, number = {}, pages = {}, doi = {10.1093/hmg/ddae179}, pmid = {40304712}, issn = {1460-2083}, support = {CA 2915/4-1//German Research Foundation/ ; }, abstract = {Neurodegenerative disorders (NDDs), characterized by a progressive loss of neurons and cognitive function, are a severe burden to human health and mental fitness worldwide. A hallmark of NDDs such as Alzheimer's disease, Huntington's disease, Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and prion diseases is disturbed cellular proteostasis, resulting in pathogenic deposition of aggregated protein species. Autophagy is a major cellular process maintaining proteostasis and integral to innate immune defenses that mediates lysosomal protein turnover. Defects in autophagy are thus frequently associated with NDDs. In this review, we discuss the interplay between NDDs associated proteins and autophagy and provide an overview over recent discoveries in inborn errors in canonical autophagy proteins that are associated with NDDs. While mutations in autophagy receptors seems to be associated mainly with the development of ALS, errors in mitophagy are mainly found to promote PD. Finally, we argue whether autophagy may impact progress and onset of the disease, as well as the potential of targeting autophagy as a therapeutic approach. Concludingly, understanding disorders due to inborn errors in autophagy-"autophagopathies"-will help to unravel underlying NDD pathomechanisms and provide unique insights into the neuroprotective role of autophagy, thus potentially paving the way for novel therapeutic interventions.}, } @article {pmid40303620, year = {2025}, author = {Basiri, K and Paydari, H and Abbasi, F and Ansari, B}, title = {Upper Extremity Peripheral Nerve Ultrasonography, as a Diagnostic Aid in Amyotrophic Lateral Sclerosis.}, journal = {Advanced biomedical research}, volume = {14}, number = {}, pages = {22}, pmid = {40303620}, issn = {2277-9175}, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a life-threatening progressive motor neuron disease whose diagnosis is challenging because of lacking specific diagnostic means. The current study aims to assess the value of upper extremity peripheral nerves ultrasonography in ALS detection.

MATERIALS AND METHODS: In this case-control study, 30 ALS subjects were assessed regarding the cross-sectional area (CSA) of the proximal (at distal part of arm or the proximal of elbow) and distal (at wrist level) median and ulnar nerves, assessed via ultrasonography. Similarly, 30 age- and gender-matched healthy controls were evaluated. The receiver operating curve (ROC) was depicted to determine a cut-point for ALS-associated peripheral nerve involvement.

RESULTS: Proximal CSA and the proximal-to-distal ratio of the median nerve was remarkably lower in both upper extremities of the ALS subjects compared to the controls (P value < 0.05), while the distal median nerve CSAs did not differ between the groups (P value > 0.05). Distal ulnar nerve CSA in the right hand (P value = 0.007) and the proximal ulnar nerve CSA in the left hand (P value = 0.001) were remarkably lower in the cases than the controls, but the other measurements did not differ (P value > 0.05). There was no significant cut-points to differentiate ALS-affected peripheral nerves from the healthy controls (P value > 0.05).

CONCLUSION: Based on this study, CSA of the proximal median nerve in the cubital fossa seems a rational and valuable means to diagnose ALS; but the distal parts of the median nerve and the ulnar nerve in its all length remained a matter of debate.}, } @article {pmid40303507, year = {2025}, author = {Verma, S and Khurana, S and Gourie-Devi, M and Anand, I and Vats, Y and Singh, A and Jothiramajayam, M and Kshetrapal, P and Sharma, A and Wajid, S and Ganguly, NK and Chakraborti, P and Taneja, V}, title = {Multiomics Approach Reveal Novel Insights in FUS Driven Juvenile Amyotrophic Lateral Sclerosis: A Family Quartet Analysis.}, journal = {Annals of neurosciences}, volume = {32}, number = {2}, pages = {78-89}, pmid = {40303507}, issn = {0972-7531}, abstract = {BACKGROUND: Juvenile amyotrophic lateral sclerosis (JALS) is a rare and severe form of motor neuron disease characterized by progressive loss of upper and lower motor neurons with an early onset (<25 years).

PURPOSE: Due to complex etiology and clinical heterogeneity, it is indispensable to unravel molecular mechanisms underlying JALS pathology. The study aimed to identify disease-specific signatures in a 14-years-old sporadic JALS patient.

METHODS: Genomic, transcriptomic, and metabolomic analysis of proband and first-degree relatives (FDR).

RESULTS: Exome sequencing identified a novel de novo frameshift variation (c.1465dupG: p.D490Gfs*26) in the fused in sarcoma (FUS) gene in proband. Interestingly, rare and potentially deleterious, disease-modifying variations in DDHD domain containing 1 (DDHD1) and fibrillin 2 (FBN2) were observed. Differentially expressed genes (DGEs) enriched in neuromuscular transmission and inflammatory response were identified by RNA-sequencing. In addition, alterations in purine and pyrimidine, vitamin B6, and sphingolipid metabolism reflect the involvement of inflammatory process in disease pathobiology.

CONCLUSION: Our findings suggest the involvement of multiple genetic factors coupled with hampered neuromuscular transmission and systemic inflammation in the onset and disease course of JALS.}, } @article {pmid40302786, year = {2025}, author = {Vijayaraghavan, M and Murali, SP and Thakur, G and Li, XJ}, title = {Role of glial cells in motor neuron degeneration in hereditary spastic paraplegias.}, journal = {Frontiers in cellular neuroscience}, volume = {19}, number = {}, pages = {1553658}, pmid = {40302786}, issn = {1662-5102}, support = {R01 NS118066/NS/NINDS NIH HHS/United States ; }, abstract = {This review provides a comprehensive overview of hereditary spastic paraplegias (HSPs) and summarizes the recent progress on the role of glial cells in the pathogenesis of HSPs. HSPs are a heterogeneous group of neurogenetic diseases characterized by axonal degeneration of cortical motor neurons, leading to muscle weakness and atrophy. Though the contribution of glial cells, especially astrocytes, to the progression of other motor neuron diseases like amyotrophic lateral sclerosis (ALS) is well documented, the role of glial cells and the interaction between neurons and astrocytes in HSP remained unknown until recently. Using human pluripotent stem cell-based models of HSPs, a study reported impaired lipid metabolisms and reduced size of lipid droplets in HSP astrocytes. Moreover, targeting lipid dysfunction in astrocytes rescues axonal degeneration of HSP cortical neurons, demonstrating a non-cell-autonomous mechanism in axonal deficits of HSP neurons. In addition to astrocytes, recent studies revealed dysfunctions in HSP patient pluripotent stem cell-derived microglial cells. Increased microgliosis and pro-inflammation factors were also observed in HSP patients' samples, pointing to an exciting role of innate immunity and microglia in HSP. Building upon these recent studies, further investigation of the detailed molecular mechanism and the interplay between glial cell dysfunction and neuronal degeneration in HSP by combining human stem cell models, animal models, and patient samples will open avenues for identifying new therapeutic targets and strategies for HSP.}, } @article {pmid40301571, year = {2025}, author = {Dragoni, F and Gerlando, RD and Diamanti, L and Rizzo, B and Bordoni, M and Scarian, E and Viola, C and Cerchia, G and Zucca, S and Pansarasa, O and Gagliardi, S}, title = {Cross-tissue MiRNA profiling of extracellular vesicles and PBMCs from amyotrophic lateral sclerosis patients.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {14976}, pmid = {40301571}, issn = {2045-2322}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology ; *MicroRNAs/genetics/metabolism ; *Extracellular Vesicles/metabolism/genetics ; *Leukocytes, Mononuclear/metabolism ; Male ; Female ; Gene Expression Profiling ; Middle Aged ; Aged ; Transcriptome ; }, abstract = {RNA-mediated toxicity, which can be controlled by alteration of gene expression, is considered a key event in Amyotrophic Lateral Sclerosis (ALS). Transcriptomic deregulation of miRNAs expression can spread via "horizontal" RNA transfer through extracellular vesicles (EVs) to act in conjunction with proteins, leading to changes in mRNA, which can provide early signals to indicate forthcoming neuropathological changes in the brain. The aim of this work is to compare expression profiles (obtained by miRNA-seq) from different tissues to highlight commonly expressed and tissue-specific miRNAs. miRNA species from plasma EVs were correlated with miRNA profiles obtained from peripheral blood mononuclear cells (PBMCs). Each tissue from ALS patients was compared to controls, revealing 159 deregulated (DE) miRNAs in Exosomes (EXOs), 247 DE miRNAs in PBMCs and 162 DE miRNAs in Microvesicles (MVs). Next, data were filtered to include only miRNAs expressed in disease samples (not in healthy subjects), to reduce the number of tissue- and ALS- specific miRNAs (EXO n = 22, MV = 11, PBMCs n = 8). We identified specific miRNAs and pathways related to each tissue. Interestingly, in PBMCs we found mainly neuro-linked pathways, such as neurotransmitters, brain and neuron development, while in EXOs, we found miRNAs implicated in MAPK and ERB signaling. In contrast, the altered pathways in MVs were not specific. This study shows that the composition of small RNA differs significantly between blood cells and its respective EVs fraction. Differentially expressed miRNAs can target definite transcripts in different cellular and molecular fractions. It is evident that, in terms of miRNAs cargo, MVs are not specific to ALS. Therefore, future studies will focus on the interaction between cells and EXOs.}, } @article {pmid40301152, year = {2025}, author = {Armas, JMB and Taoro-González, L and Fisher, EMC and Acevedo-Arozena, A}, title = {Challenges of modelling TDP-43 pathology in mice.}, journal = {Mammalian genome : official journal of the International Mammalian Genome Society}, volume = {36}, number = {2}, pages = {465-481}, pmid = {40301152}, issn = {1432-1777}, mesh = {Animals ; *DNA-Binding Proteins/genetics/metabolism ; Mice ; *Disease Models, Animal ; *TDP-43 Proteinopathies/genetics/pathology/metabolism ; Humans ; Mutation ; Amyotrophic Lateral Sclerosis/genetics/pathology ; Cell Nucleus/genetics/metabolism ; Cytoplasm/metabolism/genetics ; }, abstract = {TDP-43 is a normally nuclear RNA binding protein that under pathological conditions may be excluded from the nucleus and deposited in the cytoplasm in the form of insoluble polyubiquitinated and polyphosphorylated inclusions. This nuclear exclusion coupled with cytoplasmic accumulation is called TDP-43 pathology and contributes to a range of disorders collectively known as TDP-43 proteinopathies. These include the great majority of amyotrophic lateral sclerosis (ALS) cases, all limbic-predominant age-related TDP-43 encephalopathy (LATE), as well as up to 50% of frontotemporal lobar degeneration (FTLD) and Alzheimer's disease (AD) cases. Thus, TDP-43 pathology is a common feature underlying a wide range of neurodegenerative conditions. However, modelling it has proven to be challenging, particularly generating models with concomitant TDP-43 loss of nuclear function and cytoplasmic inclusions. Here, focussing exclusively on mice, we discuss TDP-43 genetic models in terms of the presence of TDP-43 pathology, and we consider other models with TDP-43 pathology due to mutations in disparate genes. We also consider manipulations aimed at producing TDP-43 pathology, and we look at potential strategies to develop new, much needed models to address the many outstanding questions regarding how and why TDP-43 protein leaves the nucleus and accumulates in the cytoplasm, causing downstream dysfunction and devastating disease.}, } @article {pmid40301025, year = {2025}, author = {Yamahara, N and Yoshikura, N and Yuhei, I and Shimohata, T}, title = {[Intravenous glucose infusion may have caused refeeding syndrome in a patient with advanced amyotrophic lateral sclerosis].}, journal = {Rinsho shinkeigaku = Clinical neurology}, volume = {65}, number = {5}, pages = {372-375}, doi = {10.5692/clinicalneurol.cn-002086}, pmid = {40301025}, issn = {1882-0654}, mesh = {Humans ; Female ; Aged ; *Refeeding Syndrome/etiology/chemically induced ; *Glucose/adverse effects/administration & dosage ; *Amyotrophic Lateral Sclerosis/complications ; Infusions, Intravenous/adverse effects ; Fluid Therapy ; Treatment Outcome ; }, abstract = {We present the case of a 69-year-old woman who underwent tracheostomy for advanced amyotrophic lateral sclerosis. The patient was treated with furosemide for leg edema. Body mass index was stable at 21.5 ‍kg/m[2]. The patient was admitted to our hospital after vomiting because of biliary infection. Fluid therapy with 286 ‍kcal/day of glucose was administered, followed by acute deterioration, including tachycardia (120 bpm), glucose intolerance, abdominal pain, hypophosphatemia (required intravenous phosphate supply; 60 ‍mmol/day), and hypokalemia (required intravenous potassium supply; 60 mEq/day). Refeeding syndrome was suspected, and the patient recovered with adjustments in serum electrolyte levels. We demonstrated that glucose infusion can cause refeeding syndrome in patients with advanced amyotrophic lateral sclerosis without low nutritional intake.}, } @article {pmid40300682, year = {2025}, author = {Li, Z and Xing, J}, title = {Role of sirtuins in cerebral ischemia-reperfusion injury: Mechanisms and therapeutic potential.}, journal = {International journal of biological macromolecules}, volume = {310}, number = {Pt 4}, pages = {143591}, doi = {10.1016/j.ijbiomac.2025.143591}, pmid = {40300682}, issn = {1879-0003}, mesh = {Humans ; *Sirtuins/metabolism/genetics ; *Reperfusion Injury/metabolism/drug therapy/pathology ; Animals ; *Brain Ischemia/metabolism/drug therapy/pathology ; }, abstract = {The high incidence and mortality rate of cardiac arrest (CA) establishes it as a critical clinical challenge in emergency medicine globally. Despite continuous advances in advanced life support (ALS) technology, the prognosis for patients experiencing cardiac arrest remains poor, with cerebral ischemia and reperfusion injury (CIRI) being a significant determinant of adverse neurological outcomes and increased mortality. Sirtuins (SIRTs) are a class of highly evolutionarily conserved NAD[+]-dependent histone deacylenzymes capable of regulating the expression of various cytoprotective genes to play a neuroprotective role in CIRI. SIRTs mainly regulate the levels of downstream proteins such as PGC 1-α, Nrf 2, NLRP 3, FoxOs, and PINK 1 to inhibit inflammatory response, attenuate oxidative stress, improve mitochondrial dysfunction, promote angiogenesis, and inhibit apoptosis while reducing CIRI. Natural active ingredients are widely used in regulating the protein level of SIRTs in the body because of their multi-components, multi-pathway, multi-target, and minimal toxic side effects. However, these naturally active ingredients still face many challenges related to drug targeting, pharmacokinetic properties, and drug delivery. The emergence and vigorous development of new drug delivery systems, such as nanoparticles, micromilk, and exosomes, provide strong support for solving the above problems. In the context of the rapid development of molecular biology technology, non-coding RNA (NcRNA), represented by miRNA and LncRNA, offers great potential for achieving gene-level precision medicine. In the context of multidisciplinary integration, combining SIRTs proteins with biotechnology, omics technologies, artificial intelligence, and material science will strongly promote the deepening of their basic research and expand their clinical application. This review describes the major signaling pathways of targeting SIRTs to mitigate CIRI, as well as the current research status of Chinese and Western medicine and medical means for the intervention level of SIRTs. Meanwhile, the challenges and possible solutions in the clinical application of targeted drugs are summarized. In the context of medical and industrial crossover, the development direction of SIRTs in the future is discussed to provide valuable reference for basic medical researchers and clinicians to improve the clinical diagnosis and treatment effects of CIRI.}, } @article {pmid40300213, year = {2025}, author = {Sun, Y and Vermulst, M}, title = {The hidden costs of imperfection: transcription errors in protein aggregation diseases.}, journal = {Current opinion in genetics & development}, volume = {93}, number = {}, pages = {102350}, pmid = {40300213}, issn = {1879-0380}, support = {R01 AG054641/AG/NIA NIH HHS/United States ; R01 AG075130/AG/NIA NIH HHS/United States ; R01 AG083065/AG/NIA NIH HHS/United States ; }, mesh = {Humans ; *Transcription, Genetic/genetics ; *Protein Aggregation, Pathological/genetics/pathology ; Protein Folding ; *Alzheimer Disease/genetics/pathology ; *Neurodegenerative Diseases/genetics/pathology ; *Protein Aggregates/genetics ; Amyloid/genetics ; *Amyotrophic Lateral Sclerosis/genetics/pathology ; Aging/genetics/pathology ; Prions/genetics ; Mutation ; }, abstract = {At first glance, biological systems appear to operate with remarkable precision and order. Yet, closer examination reveals that this perfection is an illusion, biological processes are inherently prone to errors. Here, we describe recent evidence that indicates that errors that occur during transcription play an important role in neurological diseases. These errors, though transient, can have lasting consequences when they generate mutant proteins with amyloid or prion-like properties. Such proteins can seed aggregation cascades, converting wild-type counterparts into misfolded conformations, ultimately leading to toxic deposits seen in diseases like Alzheimer's and amyotrophic lateral sclerosis. These observations help to paint a fuller picture of the origins of neurodegenerative diseases in aging humans and suggest a unified mechanism by which they may arise.}, } @article {pmid40299664, year = {2025}, author = {Nogueira-Machado, JA and Rocha-Silva, F and Gomes, NA}, title = {The Role of mTOR in Amyotrophic Lateral Sclerosis.}, journal = {Biomedicines}, volume = {13}, number = {4}, pages = {}, pmid = {40299664}, issn = {2227-9059}, abstract = {Background: Amyotrophic lateral sclerosis (ALS) is a rare, progressive, and incurable disease characterized by muscle weakness and paralysis. Recent studies have explored a possible link between ALS pathophysiology and mTOR signaling. Recent reports have linked the accumulation of protein aggregates, dysfunctional mitochondria, and homeostasis to the development of ALS. mTOR plays a pivotal role in controlling autophagy and affecting energy metabolism, in addition to supporting neuronal growth, plasticity, and the balance between apoptosis and autophagy, all of which are important for homeostasis. Aim: This mini-review approaches the regulatory roles of mTOR signaling pathways, their interaction with other metabolic pathways, and their potential to modulate ALS progression. Significance: It discusses how these metabolic signaling pathways affect the neuromuscular junction, producing symptoms of muscle weakness and atrophy similar to those seen in patients with ALS. The discussion includes the concepts of neurocentric and peripheral and the possible connection between mTOR and neuromuscular dysfunction in ALS. Conclusions: It highlights the therapeutic potential of mTOR signaling and interconnections with other metabolic routes, making it a promising biomarker and therapeutic target for ALS.}, } @article {pmid40299512, year = {2025}, author = {Eslami, M and Adampour, Z and Fadaee Dowlat, B and Yaghmayee, S and Motallebi Tabaei, F and Oksenych, V and Naderian, R}, title = {A Novel Frontier in Gut-Brain Axis Research: The Transplantation of Fecal Microbiota in Neurodegenerative Disorders.}, journal = {Biomedicines}, volume = {13}, number = {4}, pages = {}, pmid = {40299512}, issn = {2227-9059}, abstract = {The gut-brain axis (GBA) represents a sophisticated bidirectional communication system connecting the central nervous system (CNS) and the gastrointestinal (GI) tract. This interplay occurs primarily through neuronal, immune, and metabolic pathways. Dysbiosis in gut microbiota has been associated with multiple neurodegenerative diseases, such as Parkinson's disease (PD), Alzheimer's disease (AD), multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS). In recent years, fecal microbiota transplantation (FMT) has gained attention as an innovative therapeutic approach, aiming to restore microbial balance in the gut while influencing neuroinflammatory and neurodegenerative pathways. This review explores the mechanisms by which FMT impacts the gut-brain axis. Key areas of focus include its ability to reduce neuroinflammation, strengthen gut barrier integrity, regulate neurotransmitter production, and reinstate microbial diversity. Both preclinical and clinical studies indicate that FMT can alleviate motor and cognitive deficits in PD and AD, lower neuroinflammatory markers in MS, and enhance respiratory and neuromuscular functions in ALS. Despite these findings, several challenges remain, including donor selection complexities, uncertainties about long-term safety, and inconsistencies in clinical outcomes. Innovations such as synthetic microbial communities, engineered probiotics, and AI-driven analysis of the microbiome hold the potential to improve the precision and effectiveness of FMT in managing neurodegenerative conditions. Although FMT presents considerable promise as a therapeutic development, its widespread application for neurodegenerative diseases requires thorough validation through well-designed, large-scale clinical trials. It is essential to establish standardized protocols, refine donor selection processes, and deepen our understanding of the molecular mechanisms behind its efficacy.}, } @article {pmid40299102, year = {2025}, author = {Zhang, G and Huang, S and Wei, M and Wu, Y and Wang, J}, title = {Excitatory Amino Acid Transporters as Therapeutic Targets in the Treatment of Neurological Disorders: Their Roles and Therapeutic Prospects.}, journal = {Neurochemical research}, volume = {50}, number = {3}, pages = {155}, pmid = {40299102}, issn = {1573-6903}, support = {2023JJB140089//Guangxi Youth Science Foundation Project/ ; 82201694//the National Natural Scientific Foundation of China/ ; 2022AC21033//Guangxi Science and technology base and talent project/ ; 2022KY0349//Guangxi university young and middle-aged teachers' basic ability improvement project/ ; }, mesh = {Humans ; Animals ; *Nervous System Diseases/metabolism/drug therapy ; *Glutamate Plasma Membrane Transport Proteins/metabolism ; Glutamic Acid/metabolism ; }, abstract = {Excitatory amino acid transporters (EAATs) are pivotal regulators of glutamate homeostasis in the central nervous system and orchestrate synaptic glutamate clearance through transmembrane transport and the glutamine‒glutamate cycle. The five EAAT subtypes (GLAST/EAAT1, GLT-1/EAAT2, EAAC1/EAAT3, EAAT4, and EAAT5) exhibit spatiotemporal-specific expression patterns in neurons and glial cells, and their dysfunction is implicated in diverse neurological pathologies, including epilepsy, amyotrophic lateral sclerosis (ALS), schizophrenia, depression, and retinal degeneration. Mechanistic studies revealed that astrocytic GLT-1 deficiency disrupts glutamate clearance in ALS motor neurons, whereas GLAST genetic variants are linked to both epilepsy susceptibility and glaucomatous retinal ganglion cell degeneration. Three major challenges persist in ongoing research: ① subtype-specific regulatory mechanisms remain unclear; ② compensatory functions of transporters vary significantly across disease models; and ③ clinical translation lacks standardized evaluation criteria. The interaction mechanisms and dynamic roles of EAATs in neurological disorders were systematically investigated in this study, and an integrated approach combining single-cell profiling, stem cell-based disease modeling, and drug screening platforms was proposed. These findings lay the groundwork for novel therapeutic strategies targeting glutamate homeostasis.}, } @article {pmid40299101, year = {2025}, author = {Sarkar, S and Porel, P and Kosey, S and Aran, KR}, title = {Unraveling the role of CGRP in neurological diseases: a comprehensive exploration to pathological mechanisms and therapeutic implications.}, journal = {Molecular biology reports}, volume = {52}, number = {1}, pages = {436}, pmid = {40299101}, issn = {1573-4978}, mesh = {Humans ; *Calcitonin Gene-Related Peptide/metabolism/genetics ; Animals ; Neuroprotective Agents/pharmacology/therapeutic use/metabolism ; *Neurodegenerative Diseases/metabolism/drug therapy/pathology ; *Nervous System Diseases/metabolism ; Signal Transduction ; Receptors, Calcitonin Gene-Related Peptide/metabolism ; Oxidative Stress ; }, abstract = {Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), Multiple sclerosis (MS), Amyotrophic lateral sclerosis (ALS), and Spinal muscular atrophy (SMA) are neurodegenerative diseases (NDDs) characterized by progressive neuronal degeneration. Recent studies provide compelling information regarding the contribution of Calcitonin Gene-Related Peptide (CGRP), a potent neuropeptide, in regulating neuroinflammation, vasodilation, and neuronal survival in these disorders. This review systematically delves into the multidimensional aspects of CGRP as both a neuroprotective agent and a neurotoxic factor in NDDs. The neuroprotective effects of CGRP include suppression of inflammation, regulation of intracellular signaling pathways, and promotion of neuronal growth and survival. However, under pathological conditions, its overexpression or dysregulation is associated with oxidative stress, excitotoxicity, and neuronal death. The therapeutic use of CGRP and its receptor antagonists in migraine provides substantial evidence for CGRP's therapeutic potential, which can be further explored for the management of NDDs. However, since the bidirectional nature of CGRP effects is evident, it is crucial to gain an accurate insight into its mechanisms to target only the neuropeptide's beneficial effects while completely avoiding the undesired consequences. Further studies should focus on understanding the context-dependent activity of CGRP in the hope of designing targeted therapy for NDDs, which could gradually transform the current pharmacological management of NDDs.}, } @article {pmid40299083, year = {2025}, author = {Levison, LS and Blicher, JU and Andersen, H}, title = {Correction: Incidence and mortality of ALS: a 42-year population-based nationwide study.}, journal = {Journal of neurology}, volume = {272}, number = {5}, pages = {365}, doi = {10.1007/s00415-025-13076-2}, pmid = {40299083}, issn = {1432-1459}, } @article {pmid40298821, year = {2025}, author = {Bortolotti, M and Polito, L and Battelli, MG and Bolognesi, A}, title = {Xanthine Oxidoreductase: A Double-Edged Sword in Neurological Diseases.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {14}, number = {4}, pages = {}, pmid = {40298821}, issn = {2076-3921}, abstract = {Non-communicable neurological disorders are the second leading cause of death, and their burden continues to increase as the world population grows and ages. Oxidative stress and inflammation are crucially implicated in the triggering and progression of multiple sclerosis, Alzheimer's disease, amyotrophic lateral sclerosis, Huntington's disease, Parkinson's disease, and even stroke. In this narrative review, we examine the role of xanthine oxidoreductase (XOR) activities and products in all the above-cited neurological diseases. The redox imbalance responsible for oxidative stress could arise from excess reactive oxygen and nitrogen species resulting from the activities of XOR, as well as from the deficiency of its main product, uric acid (UA), which is the pivotal antioxidant system in the blood. In fact, with the exception of stroke, serum UA levels are inversely related to the onset and progression of these neurological disorders. The inverse correlation observed between the level of uricemia and the presence of neurological diseases suggests a neuroprotective role for UA. Oxidative stress and inflammation are also caused by ischemia and reperfusion, a condition in which XOR action has been recognized as a contributing factor to tissue damage. The findings reported in this review could be useful for addressing clinical decision-making and treatment optimization.}, } @article {pmid40298692, year = {2025}, author = {Petito, G and Del Fiore, VS and Cuomo, A and Cioffi, F and Cobellis, G and Lanni, A and Guerra, F and Bucci, C and Senese, R and Romano, R}, title = {Dysfunctional Mitochondria Characterize Amyotrophic Lateral Sclerosis Patients' Cells Carrying the p.G376D TARDBP Pathogenetic Substitution.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {14}, number = {4}, pages = {}, pmid = {40298692}, issn = {2076-3921}, support = {PRIN2022 PNRR N. P2022FBZXY//Ministero dell'università e della ricerca/ ; D.M. n. 737 of 25.06.2021//Ministero dell'università e della ricerca/ ; PRIN2022 N. 2022XTM2S3//Ministero dell'università e della ricerca/ ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease caused by the degeneration of upper and lower motor neurons in the brain, brainstem and spinal cord. About 10% of familial ALS cases are linked to pathogenetic substitution in TARDBP, the gene encoding the TDP-43 protein. A novel rare causative variant in TARDBP (p.G376D) was recently reported in ALS patients. It leads to TDP-43 cytoplasmic mislocalization, increased oxidative stress and reduced cell viability. However, functional studies on the effects of this molecular defect have not yet been carried out. Mitochondria are highly dynamic organelles, and their deregulation has emerged as a key factor in many diseases, among which is ALS. Therefore, this study aimed at determining the impact of this causative variant on mitochondria. In cellular models expressing TDP-43[G376D] and in fibroblasts derived from patients carrying this molecular defect, we observed alterations of mitochondrial functionality. We demonstrated increased localization of the mutated protein to mitochondria and a reduced abundance of subunits of complex I and complex II of the mitochondrial respiratory chain, associated with a decrease in mitochondrial membrane potential, in cellular respiration and in cytochrome C oxidase (COX) activity. Moreover, ALS cells showed increased mitochondrial fragmentation and reduced abundance of antioxidant enzymes causing increased oxidative stress. These results expand our knowledge about the molecular mechanisms underlying ALS pathogenesis associated with TDP-43 p.G376D and could help to identify new therapeutic strategies to counteract this disease.}, } @article {pmid40298207, year = {2025}, author = {Radakovic, R and Gray, D and Trucco, AP and Bregola, A and Mioshi, E and Copsey, H and Dick, D and Newton, J and Colville, S and Pal, S and Chandran, S and Simmons, Z and Abrahams, S}, title = {Impact of apathy over the course of disease in amyotrophic lateral sclerosis.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {26}, number = {5-6}, pages = {516-525}, doi = {10.1080/21678421.2025.2495020}, pmid = {40298207}, issn = {2167-9223}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/psychology/complications ; Male ; *Apathy/physiology ; Female ; Middle Aged ; *Quality of Life/psychology ; *Caregivers/psychology ; Aged ; Disease Progression ; Adult ; }, abstract = {Objective: Apathy is a common syndrome in amyotrophic lateral sclerosis (ALS), particularly Initiation apathy (lack of motivation for self-generated thoughts and/or actions). The aim was to determine how apathy subtypes change over time, and their impact on individuals' quality of life (QoL), caregiver-wellbeing and burden or strain. Methods: Forty-nine people living with ALS (pwALS) and their caregiver participated in interviews at three time-points (3-month intervals). They completed the Dimensional Apathy Scale (DAS), and assessments of depression, anxiety and emotional lability, cognitive-behavioral functioning and functional disability. PwALS QoL, caregiver burden or strain, caregiver-wellbeing and care-related QoL were measured. Results: At baseline, Initiation apathy was most common (38.8%, N = 19) followed by Emotional apathy (16.3%, N = 8). Lower caregiver-wellbeing was observed in Initiation apathy (p < 0.05) and Mixed-emotional apathy (p < 0.001) groups, where only Initiation apathy had higher caregiver burden or strain (p < 0.05) than those with no apathy. Over three visits (N = 31), there was an increase in Initiation apathy (p < 0.01) and Executive apathy (p < 0.05) over time. While controlling for functional disability, only increasing Emotional apathy was associated with increasing caregiver burden or strain (p < 0.05), decreasing caregiver-wellbeing (p < 0.001), and decreasing care-related QoL (p < 0.05). Conclusion: Initiation and Emotional apathy were variably associated with higher levels of caregiver burden or strain and decreased caregiver-wellbeing in ALS. As ALS progresses, Initiation and Executive apathy increased, while Emotional apathy has been shown to impact care-related QoL, caregiver-wellbeing and burden or strain. This has implications for understanding the progression of apathy subtypes and the interplay of caregiver-wellbeing, QoL, burden, or strain.}, } @article {pmid40297747, year = {2025}, author = {Nara, T and Shibuya, K and Ikeda, S and Kuroiwa, R and Otani, R and Ogushi, M and Suichi, T and Shiko, Y and Takahashi, K and Misawa, S and Murata, A and Kuwabara, S}, title = {Different patterns of fasciculation in spinal and bulbar muscular atrophy and amyotrophic lateral sclerosis: a muscle ultrasonographic study.}, journal = {BMJ neurology open}, volume = {7}, number = {1}, pages = {e001065}, pmid = {40297747}, issn = {2632-6140}, abstract = {BACKGROUND: The usefulness of muscle ultrasonography for detection of fasciculations has been increasingly recognised, particularly in amyotrophic lateral sclerosis (ALS). This study aimed to elucidate distributions and characteristics of fasciculations in spinal and bulbar muscular atrophy (SBMA) and to compare the results of those in ALS.

METHODS: In 24 SBMA and 16 ALS patients, muscle ultrasonography was systematically performed in the tongue, upper limb muscles (biceps brachii, triceps brachii, first dorsal interosseous (FDI), abductor pollicis brevis and abductor digiti minimi), trunk muscles (Th10 paraspinals and rectus abdominis) and lower limb muscles (vastus lateralis, biceps femoris, tibialis anterior and gastrocnemius). We assessed the presence of fasciculations and the fasciculation intensity (scored from 0 to 3) for each muscle.

RESULTS: All SBMA and ALS patients showed fasciculations at least in two muscles. In SBMA patients, fasciculations were most frequently found in the tongue (100%), FDI (93%) and tibialis anterior (80%), whereas less frequently present in the proximal limb and trunk muscles, irrespective of age, disease duration and CAG repeat numbers. By contrast, in ALS patients, fasciculations were more diffusely distributed including the proximal limb and trunk muscles. When fasciculations were present, the intensity was higher in ALS patients, except for the tongue.

CONCLUSIONS: Whereas both diseases exhibit extensive fasciculations, the distribution and intensity are different. SBMA is characterised by prominent involvement in the tongue and distal limb muscles, suggesting different pathophysiology of motor neuronal death in SBMA and ALS.}, } @article {pmid40296625, year = {2025}, author = {Barabadi, T and Mirjalili, ES and Mohamadi-Zarch, SM and Rahimi, H and Keshmirshekan, F and Bagheri, SM}, title = {Cell-Free DNA, a Noninvasive Biomarker for Prediction and Detection of Neurodegenerative Diseases, New Insights, and Perspectives.}, journal = {CNS & neurological disorders drug targets}, volume = {}, number = {}, pages = {}, doi = {10.2174/0118715273366438250408120558}, pmid = {40296625}, issn = {1996-3181}, abstract = {Neurodegenerative diseases pose serious threats to public health worldwide. Biomarkers for neurodegenerative disorders are essential to enhance the diagnostic process in clinical settings and to aid in the creation and assessment of effective disease-modifying treatments. In recent times, affordable and readily available blood-based biomarkers identifying the same neurodegenerative disease pathologies have been created, potentially transforming the diagnostic approach for these disorders worldwide. Emerging relevant biomarkers for α-synuclein pathology in Parkinson's disease include blood-based indicators of overall neurodegeneration and glial activation. Cell-free DNA (cfDNA), an encouraging non-invasive biomarker commonly utilized in oncology and pregnancy, has demonstrated significant potential in clinical uses for diagnosing neurodegenerative disorders. In this section, we explore the latest cfDNA studies related to neurodegenerative disorders. Moreover, we present a perspective on the possible role of cfDNA as a diagnostic, therapeutic, and prognostic indicator for neurodegenerative disorders. This review provides a summary of the most recent progress in biomarkers for neurodegenerative disorders such as Alzheimer's, Parkinson's disease, multiple sclerosis, amyotrophic lateral sclerosis, and traumatic brain injury.}, } @article {pmid40295933, year = {2025}, author = {Yu, SF and Michon, M and Lingappa, AF and Paulvannan, K and Solas, D and Staats, K and Ichida, J and Dey, D and Rosenfeld, J and Lingappa, VR}, title = {An ALS assembly modulator signature in peripheral blood mononuclear cells: implications for ALS pathophysiology, therapeutics, and diagnostics.}, journal = {Clinical proteomics}, volume = {22}, number = {1}, pages = {16}, pmid = {40295933}, issn = {1542-6416}, support = {IL-2023-C4-L1//Target ALS/ ; W81XWH2210721//DOD CDMRP/ ; }, abstract = {Assembly modulators are a new class of allosteric site-targeted therapeutic small molecules, some of which are effective at restoring nuclear localization of TDP-43 in ALS cellular models, and which display efficacy in a variety of ALS animal models. These compounds have been shown to bind selectively to a small subset of protein disulfide isomerase (PDI), a protein implicated in ALS pathophysiology. The targeted subset of PDI is found within a novel, transient and energy-dependent multi-protein complex that includes other important members of the ALS interactome, such as TDP-43, RanGTPase, and selective autophagy receptor p62/SQSTM1. We demonstrate here that a similar multi-protein complex drug target is present in PBMCs as isolated by energy-dependent drug resin affinity chromatography (eDRAC) and characterized by mass spectrometry and by Western blot (WB). Signature alterations in the composition of the multi-protein complex in PBMCs from ALS patients compared to PBMCs from healthy individuals were identified by WB of eDRAC bound proteins, thereby extending earlier literature suggesting PBMC dysfunction in ALS. Changes in the PBMC drug target in ALS patients compared to healthy individuals include diminished p62/SQSTM1 and appearance of a 17 kDa post-translationally modified form of RanGTPase. These changes are not readily apparent from analysis of whole cell extracts, as the individual protein components within the drug target multi-protein complex comprise only small percentages of the total of those component proteins in the extract. Furthermore, whole blood from ALS patients shows a distinctive degradation of total RanGTPase not observed in blood from healthy individuals. This degradation appears to be rescued by treatment of whole blood from ALS patients for 72 h with ALS-active assembly modulator small molecules. Our findings are consistent with the hypothesis that ALS is fundamentally a disorder of homeostasis that can be detected early, prior to disability, in blood by the methods described, and restored to the healthy state by assembly modulator drug treatment.}, } @article {pmid40295825, year = {2025}, author = {Hu, X and Xu, Y and Li, C and Mao, H and Liu, Z and Xiao, Y and Li, Y and Yang, X}, title = {A five-year examination into the occurrence of herbicide-resistant barnyardgrass populations in paddy from Jiangsu Province, China.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {14781}, pmid = {40295825}, issn = {2045-2322}, support = {2023YFD1401100//National Key Research and Development Program of China/ ; 2023YFD1401100//National Key Research and Development Program of China/ ; 2023YFD1401100//National Key Research and Development Program of China/ ; 2023YFD1401100//National Key Research and Development Program of China/ ; 2023YFD1401100//National Key Research and Development Program of China/ ; 2023YFD1401100//National Key Research and Development Program of China/ ; 2023YFD1401100//National Key Research and Development Program of China/ ; 2023YFD1401100//National Key Research and Development Program of China/ ; 32272565//National Natural Science Foundation of China/ ; 32272565//National Natural Science Foundation of China/ ; 32272565//National Natural Science Foundation of China/ ; 32272565//National Natural Science Foundation of China/ ; 32272565//National Natural Science Foundation of China/ ; 32272565//National Natural Science Foundation of China/ ; 32272565//National Natural Science Foundation of China/ ; 32272565//National Natural Science Foundation of China/ ; }, mesh = {*Herbicide Resistance/genetics ; China ; *Herbicides/pharmacology ; *Echinochloa/drug effects/genetics ; *Oryza/growth & development ; Quinolines ; }, abstract = {To assess resistance situation and evolutionary risks, 510 Echinochloa populations from 13 rice-growing regions in Jiangsu Province (2018-2022) were tested against seven herbicides (penoxsulam, quinclorac, cyhalofop-butyl, bispyribac-sodium, pretilachlor, metamifop, and florpyrauxifen-benzyl), with cross- and multiple-resistance patterns analyzed. Penoxsulam resistance increased ninefold over five years, while quinclorac resistance consistently exceeded 40% annually for four years. Cyhalofop-butyl and bispyribac-sodium resistance frequencies also rose annually, with the strongest resistance to penoxsulam and bispyribac-sodium observed in southern Jiangsu, particularly in Suzhou, Wuxi, Changzhou, and Zhenjiang. In northern Jiangsu, Huaian showed the highest resistance to multiple herbicides, while quinclorac resistance was widespread across all regions. Pretilachlor and metamifop resistance remained low, with only sporadic outbreaks, indicating that they continued to be used. However, prolonged use of single-site herbicides, particularly ALS inhibitors and ACCase inhibitors, has led to cross-resistance evolution. Multiple-resistance analysis indicated that quinclorac, penoxsulam, and cyhalofop-butyl should not be used in binary or ternary mixtures to control resistant Echinochloa. Notably, 14 populations exhibited florpyrauxifen-benzyl resistance, with 13 also showing quinclorac resistance, suggesting a potential link between prior quinclorac resistance and florpyrauxifen-benzyl resistance evolution, which warrants further investigation. This study clarifies herbicide resistance patterns in Echinochloa in Jiangsu Province, offering critical insights for resistance management strategies.}, } @article {pmid40295163, year = {2025}, author = {Miyachi, S and Oshima, Y and Yazaki, K and Futaki, N and Shirai, Y and Tanei, ZI and Ikebe, Y and Iwata, I and Ujiie, H and Onozawa, M and Hirano, S and Tanaka, S and Yabe, I}, title = {An Autopsy Case of Amyotrophic Lateral Sclerosis With Sudden Death Showed Histological Features of Lewy Body Disease.}, journal = {Neuropathology : official journal of the Japanese Society of Neuropathology}, volume = {45}, number = {4}, pages = {e70009}, doi = {10.1111/neup.70009}, pmid = {40295163}, issn = {1440-1789}, support = {//Mitsubishi Foundation Research Grant for Social Welfare Activities/ ; }, mesh = {Humans ; Male ; Aged, 80 and over ; *Amyotrophic Lateral Sclerosis/pathology/complications ; *Lewy Body Disease/pathology/complications ; Autopsy ; *Death, Sudden/etiology/pathology ; Fatal Outcome ; *Brain/pathology ; }, abstract = {We present the case of an 81-year-old man diagnosed with probable amyotrophic lateral sclerosis (ALS) based on the Updated Awaji criteria. The patient exhibited progressive motor neuron degeneration with muscle weakness, atrophy, and fasciculations primarily in the right lower limb and later extending to the right upper limb. Three months after being referred to a home care clinic, he collapsed in front of his family members and died. An autopsy revealed phosphorylated TDP-43 pathology consistent with ALS, with involvement of the hypoglossal nucleus, facial nerve nucleus, and medulla oblongata. Interestingly, widespread a-synuclein pathology indicative of diffuse neocortical type Lewy body disease (LBD; Braak stage 6) was identified, despite the absence of clinical parkinsonism or dementia with Lewy bodies (DLB) during his lifetime. The presence of autonomic symptoms such as constipation and urinary retention shortly before death may be attributable to a-synuclein pathology affecting the autonomic nervous system. The coexistence of ALS and LBD underscores the clinical challenge of diagnosing overlapping pathologies, as motor symptoms may obscure signs of LBD. Dopamine transporter imaging or MIBG myocardial scintigraphy might aid in identifying preclinical LBD in ALS patients with atypical symptoms. The patient died of respiratory failure due to extensive organizing pneumonia, but the possibility of sudden cardiac arrest could not be excluded. This case highlights the potential for coexisting neurodegenerative pathologies in ALS, emphasizing the importance of comprehensive evaluation when autonomic symptoms or other atypical features are present.}, } @article {pmid40295049, year = {2025}, author = {Keul, J and Sperling, S and Rohde, V and Ninkovic, M}, title = {Advantages and Disadvantages of Drug Combination Treatment: Riluzole, Metformin and Dexamethasone Effect on Glioblastoma Cell.}, journal = {Anticancer research}, volume = {45}, number = {5}, pages = {1813-1823}, doi = {10.21873/anticanres.17561}, pmid = {40295049}, issn = {1791-7530}, mesh = {Humans ; *Glioblastoma/drug therapy/pathology/metabolism/genetics ; *Metformin/pharmacology/administration & dosage ; *Dexamethasone/pharmacology/administration & dosage ; Cell Line, Tumor ; *Riluzole/pharmacology/administration & dosage ; *Brain Neoplasms/drug therapy/pathology/metabolism ; Cell Movement/drug effects ; Cell Survival/drug effects ; *Antineoplastic Combined Chemotherapy Protocols/pharmacology ; Matrix Metalloproteinase 2/metabolism ; Drug Synergism ; Cell Proliferation/drug effects ; }, abstract = {BACKGROUND/AIM: In glioblastoma multiforme (GBM), a deadly brain tumor, glucose is one of the main fuels for accelerated growth. Patients with GBM are also exposed to excess glucose through hyperglycemia in diabetes mellitus. In addition, dexamethasone (Dex), a corticosteroid commonly administered for controlling cerebral oedema, causes additional excess glucose. Therefore, targeting glucose metabolism is an attractive therapeutic intervention for GBM treatment. We have recently shown that riluzole (Ril), a drug used to treat amyotrophic lateral sclerosis (ALS), has an effect on some detrimental Dex-induced metabolic changes in GBM. Therefore, we examined the effect of the combination of metformin (Met), widely used to treat type 2 diabetes, and Ril on GBM cells.

MATERIALS AND METHODS: The 3-(4, 5-dimethylthiazol)-2, 5-diphenyltetrazolium bromide (MTT) assay was used to determine cell viability of U87MG after treatment with Ril, Met, Ril plus Met (Ril+Met) and the addition of Dex to this co-treatment. Cell migration was assessed by the xCELLigence system, matrix metalloproteinase 2 (MMP2) activation by zymography assay and gene expression by real-time polymerase chain reaction (RT-PCR).

RESULTS: Co-treatment with Ril and Met was effective in killing GBM cells and reducing the expression of genes involved in glucose and stem cell metabolism. Furthermore, combination of Ril and Met reduced MMP2 activation. But co-administration increased the migration of U87MG cells. The addition of Dex to this combination reversed the unfavorable effects of Ril+Met on cell migration.

CONCLUSION: Ril+Met co-treatment had a positive effect in terms of GBM cell death, decreased expression of genes involved in glucose metabolism and stemness, and reduced MMP2 activation. Disadvantage of Ril+Met treatment was increased cell migration. Taken together, these drug combinations may also allow the reduction of the concentration of Dex to minimize its side effects.}, } @article {pmid40294721, year = {2025}, author = {Natala, SR and Habas, A and Stocking, EM and Orry, A and Abagyan, R and Makale, MT and Wrasidlo, W}, title = {Structure based design, synthesis and identification of novel covalent reversible dual TLR2/TLR9 small molecule antagonists.}, journal = {Bioorganic & medicinal chemistry letters}, volume = {124}, number = {}, pages = {130259}, doi = {10.1016/j.bmcl.2025.130259}, pmid = {40294721}, issn = {1464-3405}, mesh = {*Toll-Like Receptor 2/antagonists & inhibitors/metabolism ; Humans ; *Drug Design ; *Toll-Like Receptor 9/antagonists & inhibitors/metabolism ; *Small Molecule Libraries/pharmacology/chemistry/chemical synthesis ; Molecular Structure ; Structure-Activity Relationship ; Animals ; Dose-Response Relationship, Drug ; }, abstract = {Inflammation is a key driver of the onset and progression of neurodegenerative diseases and cancer and can be caused by aggregated proteins, injured neurons or synapses, dysregulation of inflammatory control mechanisms, and other factors. Tolllike receptors (TLRs) are important mediators of inflammatory pathways, and their activation leads to pro-inflammatory cytokine release by immune cells in the periphery or in the central nervous system (CNS). TLR2 and TLR9 are implicated in the inflammatory pathogenesis of CNS degenerative diseases such as Parkinson's Disease (PD) and amyotrophic lateral sclerosis (ALS). They are also held to be important in the etiology of certain malignancies like inflammatory pancreatic ductal adenocarcinoma and glioblastoma. Inactivation of TLR2/9 in animal models of neurodegeneration has reduced pathological markers and diminished neuronal loss, while in animal models of cancer it has suppressed tumors. Therefore, TLR2 and TLR9 may be potential targets for the treatment of neurodegenerative disorders and cancers. We identified for the first time a key binding locus in TLR2/9 TIR domain which guided reversible covalent drug (RCD) design of a novel, first-in class series of dual TLR2/9 antagonists. Sub-micromolar antagonist concentrations potently inhibited TLR2 and TLR9 signaling induced by TLR2/9 specific agonists. Importantly, this series of antagonists did not discernably activate other TLRs and exhibited favorable in-vitro ADME and safety. The analogs described here may help realize effective TLR2/9 antagonism as a viable therapeutic strategy for inflammation driven CNS diseases and various malignancies with an inflammatory etiology.}, } @article {pmid40294208, year = {2025}, author = {Winek, K and Soreq, H}, title = {Emerging roles of transfer RNA fragments in the CNS.}, journal = {Brain : a journal of neurology}, volume = {148}, number = {8}, pages = {2631-2645}, pmid = {40294208}, issn = {1460-2156}, support = {5P01AG014449-21/GF/NIH HHS/United States ; 11183//Israel Science Foundation/ ; 835/23//Israel Science Foundation/ ; P01 AG014449/AG/NIA NIH HHS/United States ; 3213/19//Israel Science Foundation/ ; 1770/20//Israel Science Foundation/ ; }, mesh = {Humans ; *RNA, Transfer/metabolism/genetics ; Animals ; *Central Nervous System/metabolism ; *Central Nervous System Diseases/genetics/metabolism ; *RNA, Small Untranslated/metabolism/genetics ; }, abstract = {Transfer RNA-derived small RNAs (tsRNAs), previously considered inactive tRNA degradation products, have now been shown to be functional small non-coding RNAs. They may play important roles within the CNS and in brain-body interactions, both during normal developmental stages as well as in diverse brain pathologies. Among the cell types found in the CNS, tsRNAs are particularly abundant in neurons. Correspondingly, neurons show cell type specific tRNA expression profiles when compared to other cells of the CNS under homeostatic conditions and defects in tRNA processing may lead to neurological disorders. Disease-specific tsRNA profiles have been identified in a number of CNS disorders, including amyotrophic lateral sclerosis and epilepsy. Elevated levels of specific tsRNAs have been found in the blood before the onset of epileptic seizures; and age-related, sex-specific loss of mitochondrial genome-originated tsRNAs in the nucleus accumbens of female patients is correlated with accelerated cognitive deterioration in Alzheimer's disease. Disease-related tsRNA signatures have also been identified in the CSF of patients with Parkinson's disease, and nucleated blood cells from ischaemic stroke patients show specific elevation of cholinergic-targeted tsRNAs. The mechanisms of action of tsRNAs are still being elucidated but include targeting complementary mRNA to impact RNA levels and translation in a miRNA-like manner, direct interaction with RNA binding proteins, or interference with translation machinery. The function of tsRNAs may be affected by the chemical modifications they inherit from the originating tRNA molecules, which impact tsRNAs production and may modulate their interactions with proteins. Research on the genetics, biochemical properties and regulatory roles of tsRNAs has expanded rapidly in recent years, facilitated by novel sequencing strategies, which include the removal of tRNA modifications and chemically blocked ends that hinder amplification and adapter ligation. Future in-depth profiling of tsRNAs levels, mode(s) of function, and identification of interacting proteins and RNAs may together shed light on the impact of tsRNAs on neuronal function, and enable novel diagnostics/therapeutics avenues for brain diseases in age, sex and disease-specific manner.}, } @article {pmid40294152, year = {2025}, author = {Alfano, LN and Iammarino, MA and Reash, NF and Lowes, LP and Pietruszewski, L and Adderley, K and Humphrey, L and Knight, AB and Steiner, CL and Smith, MA and Sahenk, Z and Connolly, AM and Almomen, M and D'Ambrosio, ES and Peck, N and Peck, A}, title = {Validity and Reliability of Clinical and Patient-Reported Outcomes in Multisystem Proteinopathy 1.}, journal = {Annals of clinical and translational neurology}, volume = {12}, number = {7}, pages = {1324-1333}, pmid = {40294152}, issn = {2328-9503}, support = {//Cure VCP Disease Inc/ ; }, mesh = {Humans ; *Patient Reported Outcome Measures ; Male ; Female ; Middle Aged ; Aged ; Reproducibility of Results ; *Valosin Containing Protein/genetics ; *Outcome Assessment, Health Care/standards ; Adult ; }, abstract = {OBJECTIVE: Valosin-containing protein (VCP)-associated multisystem proteinopathy 1 (MSP1) is caused by variants in the VCP gene. MSP1 results in various phenotypes including progressive myopathy, Paget's disease of bone, frontotemporal dementia, amyotrophic lateral sclerosis, and parkinsonism, among others. Our study aimed to validate functional clinical outcome assessments (COA) and patient-reported outcomes (PRO) to inform clinical care practices and future clinical trial design. In addition, we evaluated the test-retest reliability of these COAs within clinics and remote environments.

METHODS: Patients completed a battery of COA and PRO across a 2-day traditional onsite visit and a 2-day remote visit within their home environment. All COA and PRO deemed safe and feasible to complete based on participants' level of function and/or home environment were collected at each visit.

RESULTS: Forty-six total patients enrolled in our study, 34 in our full study and 12 in an expanded remote-only cohort. Functional COA measured decline over reported disease duration in this cross-sectional group and significantly correlated with PRO (rho > 0.5, p < 0.001). Differences in lower and upper extremity involvement were noted across variant groups. Performance of functional COA was reliable and safe within and across onsite and remote testing environments (ICC > 0.7, p < 0.001).

INTERPRETATION: Functional COA and PRO are valid and reliable to measure abilities in participants with MSP1. Testing can be completed reliably within the home, which could expand equitable access to clinical care and/or future clinical trial participation. Prospective longitudinal data collection is ongoing to understand outcome sensitivity and meaningful change over time.}, } @article {pmid40293530, year = {2025}, author = {Shahidehpour, RK and Katsumata, Y and Dickson, DW and Ghayal, NB and Aung, KZ and Wu, X and Phe, P and Jicha, GA and Neltner, AM and Archer, JRC and Corrada, MM and Kawas, CH and Ahmad Sajjadi, S and Woodworth, DC and Bukhari, SA and Montine, TJ and Fardo, DW and Nelson, PT}, title = {LATE-NC Stage 3: a diagnostic rubric to differentiate severe LATE-NC from FTLD-TDP.}, journal = {Acta neuropathologica}, volume = {149}, number = {1}, pages = {38}, pmid = {40293530}, issn = {1432-0533}, support = {P50 AG008671/AG/NIA NIH HHS/United States ; P30 AG072972/AG/NIA NIH HHS/United States ; R01 AG057187/AG/NIA NIH HHS/United States ; P30 AG013854/AG/NIA NIH HHS/United States ; P50 MH060451/MH/NIMH NIH HHS/United States ; P20 AG068082/AG/NIA NIH HHS/United States ; P30 AG072975/AG/NIA NIH HHS/United States ; P30 AG066444/AG/NIA NIH HHS/United States ; R01 AG022374/AG/NIA NIH HHS/United States ; P30 AG010124/AG/NIA NIH HHS/United States ; P50 AG023501/AG/NIA NIH HHS/United States ; U01 HG006375/HG/NHGRI NIH HHS/United States ; P30 AG066507/AG/NIA NIH HHS/United States ; P30 AG072946/AG/NIA NIH HHS/United States ; P30 AG066518/AG/NIA NIH HHS/United States ; RC2 AG036528/AG/NIA NIH HHS/United States ; R01 AG021055/AG/NIA NIH HHS/United States ; P30 AG028377/AG/NIA NIH HHS/United States ; P50 AG005142/AG/NIA NIH HHS/United States ; R01 AG061111/AG/NIA NIH HHS/United States ; R01 AG035137/AG/NIA NIH HHS/United States ; R01 AG061111, R01 AG057187, P30 AG072946, RF1 NS118584, T32 AG078110, R01 AG021055, P30 AG066519//National Institutes on Health, United States/ ; P50 AG005131/AG/NIA NIH HHS/United States ; P50 AG005128/AG/NIA NIH HHS/United States ; P30 AG010133/AG/NIA NIH HHS/United States ; U24 AG021886/AG/NIA NIH HHS/United States ; R01 AG031581/AG/NIA NIH HHS/United States ; P50 AG016574/AG/NIA NIH HHS/United States ; P30 AG066511/AG/NIA NIH HHS/United States ; P30 AG086404/AG/NIA NIH HHS/United States ; P50 AG005146/AG/NIA NIH HHS/United States ; U24 AG072122/AG/NIA NIH HHS/United States ; P30 AG066512/AG/NIA NIH HHS/United States ; R01 AG019085/AG/NIA NIH HHS/United States ; U01 AG032984/AG/NIA NIH HHS/United States ; P30 AG066515/AG/NIA NIH HHS/United States ; R01 AG013616/AG/NIA NIH HHS/United States ; P30 AG062421/AG/NIA NIH HHS/United States ; R01 AG030146/AG/NIA NIH HHS/United States ; U01 AG024904/AG/NIA NIH HHS/United States ; P50 AG008702/AG/NIA NIH HHS/United States ; RF1 NS118584/NS/NINDS NIH HHS/United States ; UL1 RR029893/RR/NCRR NIH HHS/United States ; U01 AG016976/AG/NIA NIH HHS/United States ; P50 NS039764/NS/NINDS NIH HHS/United States ; P30 AG066508/AG/NIA NIH HHS/United States ; P01 AG003991/AG/NIA NIH HHS/United States ; P30 AG008051/AG/NIA NIH HHS/United States ; P50 AG005681/AG/NIA NIH HHS/United States ; P30 AG013846/AG/NIA NIH HHS/United States ; RC2 AG036502/AG/NIA NIH HHS/United States ; P30 AG072978/AG/NIA NIH HHS/United States ; R01 AG017917/AG/NIA NIH HHS/United States ; P30 AG062429/AG/NIA NIH HHS/United States ; P30 AG066519/AG/NIA NIH HHS/United States ; R01 MH080295/MH/NIMH NIH HHS/United States ; P50 AG005136/AG/NIA NIH HHS/United States ; P30 AG072973/AG/NIA NIH HHS/United States ; P30 AG012300/AG/NIA NIH HHS/United States ; P30 AG062422/AG/NIA NIH HHS/United States ; R01 AG079280/AG/NIA NIH HHS/United States ; R01 AG012101/AG/NIA NIH HHS/United States ; P50 AG016573/AG/NIA NIH HHS/United States ; P30 AG086401/AG/NIA NIH HHS/United States ; P50 AG016570/AG/NIA NIH HHS/United States ; P50 AG005134/AG/NIA NIH HHS/United States ; P30 AG066462/AG/NIA NIH HHS/United States ; P30 AG008017/AG/NIA NIH HHS/United States ; U24 AG041689/AG/NIA NIH HHS/United States ; P01 AG019724/AG/NIA NIH HHS/United States ; R01 AG062706/AG/NIA NIH HHS/United States ; P30 AG010161/AG/NIA NIH HHS/United States ; P30 AG066530/AG/NIA NIH HHS/United States ; R01 AG033193/AG/NIA NIH HHS/United States ; P50 AG025688/AG/NIA NIH HHS/United States ; R37 AG015473/AG/NIA NIH HHS/United States ; U24 AG026395/AG/NIA NIH HHS/United States ; P50 AG005133/AG/NIA NIH HHS/United States ; U01 AG010483/AG/NIA NIH HHS/United States ; P30 AG066509/AG/NIA NIH HHS/United States ; P01 AG002219/AG/NIA NIH HHS/United States ; R01 CA129769/CA/NCI NIH HHS/United States ; T32 AG078110/AG/NIA NIH HHS/United States ; U01 AG006781/AG/NIA NIH HHS/United States ; R01 AG041797/AG/NIA NIH HHS/United States ; P50 AG005144/AG/NIA NIH HHS/United States ; P01 AG010491/AG/NIA NIH HHS/United States ; P30 AG066546/AG/NIA NIH HHS/United States ; P50 AG005138/AG/NIA NIH HHS/United States ; R01 AG021547/AG/NIA NIH HHS/United States ; R01 AG041232/AG/NIA NIH HHS/United States ; R01 AG019757/AG/NIA NIH HHS/United States ; R01 AG020688/AG/NIA NIH HHS/United States ; P30 AG072977/AG/NIA NIH HHS/United States ; P30 AG062677/AG/NIA NIH HHS/United States ; R01 AG030653/AG/NIA NIH HHS/United States ; R01 AG027944/AG/NIA NIH HHS/United States ; P30 AG072958/AG/NIA NIH HHS/United States ; R01 AG017173/AG/NIA NIH HHS/United States ; R01 AG025259/AG/NIA NIH HHS/United States ; P30 AG062715/AG/NIA NIH HHS/United States ; U01 HG004610/HG/NHGRI NIH HHS/United States ; /WT_/Wellcome Trust/United Kingdom ; P30 AG066506/AG/NIA NIH HHS/United States ; P30 AG066468/AG/NIA NIH HHS/United States ; P30 AG072976/AG/NIA NIH HHS/United States ; P30 AG010129/AG/NIA NIH HHS/United States ; P30 AG019610/AG/NIA NIH HHS/United States ; P50 AG016582/AG/NIA NIH HHS/United States ; R01 AG041718/AG/NIA NIH HHS/United States ; P30 AG072947/AG/NIA NIH HHS/United States ; P30 AG072931/AG/NIA NIH HHS/United States ; P30 AG066514/AG/NIA NIH HHS/United States ; P30 AG072959/AG/NIA NIH HHS/United States ; P30 AG028383/AG/NIA NIH HHS/United States ; RF1 AG082339/AG/NIA NIH HHS/United States ; R01 AG026916/AG/NIA NIH HHS/United States ; P50 AG033514/AG/NIA NIH HHS/United States ; R01 NS059873/NS/NINDS NIH HHS/United States ; P30 AG072979/AG/NIA NIH HHS/United States ; R01 AG015819/AG/NIA NIH HHS/United States ; }, mesh = {Humans ; Male ; Female ; Aged ; *Frontotemporal Lobar Degeneration/pathology/diagnosis/genetics ; *TDP-43 Proteinopathies/pathology/diagnosis/genetics ; Diagnosis, Differential ; Aged, 80 and over ; DNA-Binding Proteins/metabolism/genetics ; Middle Aged ; *Brain/pathology ; Inclusion Bodies/pathology ; Dementia ; }, abstract = {A diagnostic rubric is required to distinguish between limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) and frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-TDP). In LATE-NC Stage 3, TDP-43 proteinopathy is present in the middle frontal gyrus (MFG), thus posing a potential diagnostic challenge in differentiating these severe LATE-NC cases from FTLD-TDP. LATE-NC Stage 3 cases and other TDP-43 proteinopathies were analyzed from the University of Kentucky (total n = 514 with TDP-43 pathology assessed), The 90+ Study at the University of California Irvine (n = 458), and the Mayo Clinic (n = 5067) brain banks. Digital pathology was used to quantify pathology burden in a select subset of cases (n = 51), complemented by a previously-described manual counting method and expert neuropathologic examinations to evaluate qualitative features such as FTLD-TDP types and subtypes of neuronal cytoplasmic inclusions (NCIs). To evaluate clinical and genetic characteristics of LATE-NC Stage 3, data were analyzed from the National Alzheimer's Coordinating Center (NACC) Neuropathology Data set and correlated with findings from the Alzheimer's Disease Genetics Consortium (ADGC). When using TDP-43 proteinopathy quantification in the MFG as a diagnostic criterion, more than 90% of cases could be classified as either LATE-NC Stage 3 or FTLD-TDP. Diagnostically challenging scenarios included a subset of FTLD-TDP Type B cases with relatively mild MFG TDP-43 pathology and a novel non-LATE-NC, non-FTLD-TDP pathologic subtype with severe MFG TDP-43 pathology. Taking these potential pitfalls into account, a classification schema was developed that could correctly diagnose all included cases. There was no difference in the Alzheimer's disease pathological load in LATE-NC Stages 2 versus 3. In genetic analyses, the GRN (rs5848) risk allele was preferentially associated with LATE-NC Stage 3, whereas TMEM106B and APOE risk-associated variants were not. In conclusion, LATE-NC Stage 3 could be differentiated reliably from FTLD-TDP and other TDP-43-opathies, based on a data-driven diagnostic rubric.}, } @article {pmid40291738, year = {2025}, author = {Zhu, B and Van, R and Wang, H and Kuang, S and Jia, Y and Leon, EC and Yang, F and Zhang, J and Yang, J and Hong, H and Fleur Marie, L and Yu, A and Wang, J and Tanzi, RE and Zhang, CM and Mao, XM and Shao, Y and Ran, C}, title = {Highly sensitive chemiluminescence imaging of misfolded proteins in neurodegenerative models.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2025.04.12.648090}, pmid = {40291738}, issn = {2692-8205}, abstract = {Protein misfolding is a crucial pathological phenomenon driving neurodegenerative diseases that affect millions of people. Visualizing misfolded proteins would greatly facilitate early diagnosis, etiology elucidation, and therapy monitoring of neurodegeneration. Although several probes have been reported, versatile and sensitive detection in vivo is still challenging. We demonstrated that both generic and precise detection of misfolded proteins could be achieved with a chemiluminescence probe, ADLumin-1. For generic aspect, ADLumin-1 was highly sensitive to various misfolded proteins, showing up to 127.73-fold higher signal-to-noise ratio than gold standard dye of Thioflavin T. ADLumin-1 could also non-invasively visualize misfolded proteins in mouse models of Parkinson's disease, Alzheimer's disease, and amyotrophic lateral sclerosis. For precise aspects, ADLumin-1 can selectively detect α-synuclein in CSF at the femtomolar level by combining with protein misfolding cyclic amplification technology in vitro. In addition, ADLumin-1 enables selective in vivo imaging of misfolded α-synuclein in transgenic mice models by employing bioorthogonal chemiluminescence resonance energy transfer strategy. Combining generality and precision, our findings could be widely applied in preclinical and clinical studies of neurodegenerative diseases.}, } @article {pmid40291716, year = {2025}, author = {Hnath, B and Dokholyan, NV}, title = {Novel extracellular vesicle release pathway facilitated by toxic superoxide dismutase 1 oligomers.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2025.04.07.647611}, pmid = {40291716}, issn = {2692-8205}, abstract = {Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease resulting in paralysis and death within three to five years. Mutations in over forty different proteins have been linked to ALS, leading to controversy whether ALS is one disease or many diseases with a similar phenotype. Mutations in Cu,Zn superoxide dismutase 1 (SOD1) are only found in 2-3% of ALS cases, yet misfolded SOD1 is found in both sporadic (sALS) and familial (fALS) patients. Yet, mutations in TDP-43 or FUS increase the level of misfolded SOD1 on extracellular vesicles (EVs). Additionally, small EVs isolated from ALS patient samples caused cell death of wild type motor neurons and myotubules. The toxicity and protein alterations of ALS EVs have led to the theory that EVs are responsible for the spread of ALS. We hypothesize that previously-identified toxic trimeric SOD1 is spreading on EVs in ALS and altering the spread of other ALS-related proteins, linking them to a common mechanism. To test our hypothesis, we isolate EVs from motor neuron-like cells expressing trimer stabilizing mutations and perform a sandwich enzyme-linked immunoassay (ELISA) (CD9 capture antibody) to quantify whether misfolded SOD1 and 17 other ALS-related proteins increase or decrease on EVs with trimer stabilization. We identify which EV release pathway is being affected by trimeric SOD1 utilizing endocytosis and exocytosis inhibitors, and determine if any specific EV-related proteins are altered with trimer stabilization. We establish that VAPB, VCP, and Stathmin-2 increase on EVs with trimer stabilization. The common pathway between SOD1 and three other ALS-associated proteins is affected by multiple pathways, including the Caveolae endocytosis pathway, suggesting a novel hybrid pathway of EV release present in ALS.}, } @article {pmid40291709, year = {2025}, author = {Gao, G and Sumrall, ER and Walter, NG}, title = {Nanoscale domains govern local diffusion and aging within FUS condensates.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2024.04.01.587651}, pmid = {40291709}, issn = {2692-8205}, abstract = {Biomolecular condensates regulate cellular physiology by sequestering and processing RNAs and proteins, yet how these processes are locally tuned within condensates remains unclear. Moreover, in neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), condensates undergo liquid-to-solid phase transitions, but capturing early intermediates in this process has been challenging. Here, we present a surface multi-tethering approach to achieve intra-condensate single-molecule tracking of fluorescently labeled RNA and protein molecules within liquid-like condensates. Using RNA-binding protein Fused in Sarcoma (FUS) as a model for condensates implicated in ALS, we discover that RNA and protein diffusion is confined within distinct nanometer-scale domains, or nanodomains, which exhibit unique connectivity and chemical environments. During condensate aging, these nanodomains reposition, facilitating FUS fibrilization at the condensate surface, a transition enhanced by FDA-approved ALS drugs. Our findings demonstrate that nanodomain formation governs condensate function by modulating biomolecule sequestration and percolation, offering insights into condensate aging and disease-related transitions.}, } @article {pmid40291645, year = {2025}, author = {Xie, L and Zhu, Y and Hurtle, BT and Wright, M and Robinson, JL and Mauna, JC and Brown, EE and Ngo, M and Bergmann, CA and Xu, J and Merjane, J and Gleixner, AM and Grigorean, G and Liu, F and Rossoll, W and Lee, EB and Kiskinis, E and Chikina, M and Donnelly, CJ}, title = {Context-dependent Interactors Regulate TDP-43 Dysfunction in ALS/FTLD.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2025.04.07.646890}, pmid = {40291645}, issn = {2692-8205}, abstract = {TDP-43 mislocalization, aggregation, and loss of splicing function are neuropathological hallmarks in over 97% of Amyotrophic Lateral Sclerosis (ALS), 45% of Frontotemporal Lobar Degeneration (FTLD), and 60% of Alzheimer's Disease, which has been reclassified as LATE-NC. However, the mechanisms underlying TDP-43 dysfunction remain elusive. Here, we utilize APEX2-driven proximity labeling and mass spectrometry to characterize the context-dependent TDP-43 interactome in conditions of cytoplasmic mislocalization, impaired RNA-binding contributing to aggregation, and oxidative stress. We describe context-dependent interactors, including disrupted interactions with splicing-related proteins and altered biomolecular condensate (BMC) associations. By integrating ALS and FTLD snRNA-seq data, we uncover disease-relevant molecular alterations and validate our dataset through a functional screen that identifies key TDP- 43 regulators. We demonstrate that disrupting nuclear speckle integrity, particularly through the downregulation of the splicing factor SRRM2, promotes TDP-43 mislocalization and loss of function. Additionally, we identify NUFIP2 as an interactor associated with mislocalization that sequesters TDP-43 into cytoplasmic aggregates and co-localizes with TDP-43 pathology in patient tissue. We also highlight HNRNPC as a potent TDP-43 splicing regulator, where precise modulation of TDP-43 or HNRNPC can rescue cryptic exon splicing. These findings provide mechanistic insights and potential therapeutic targets for TDP-43 dysfunction.}, } @article {pmid40290690, year = {2025}, author = {Cao, YK and Yang, SL and Wei, ZQ}, title = {Is the use of a transanal drainage tube effective in treating anastomotic leakage for mid-low rectal cancer.}, journal = {World journal of clinical oncology}, volume = {16}, number = {4}, pages = {99801}, pmid = {40290690}, issn = {2218-4333}, abstract = {BACKGROUND: Anastomotic leakage (AL) is a severe surgical complication for mid-low rectal cancers. The efficacy of transanal drainage tube (TDT) has rarely been reported.

AIM: To evaluate the efficacy of TDT after AL.

METHODS: A retrospective analysis was conducted on 68 patients with mid-low rectal cancer who underwent laparoscopic low anterior resection (LAR) and developed ALs. Leakage were identified using imaging studies and digital rectal examinations when local abscesses or systemic infections were present. In each patient, the leakage site was determined using the index finger and a drainage tube was inserted transanally to drain the abscesses and exudates outside the anus. The clinical outcomes of the patients following transanal drainage were analyzed.

RESULTS: A total of 43 patients received TDT treatment, while 25 patients did not receive TDT treatment. Among the patients in the TDT group, 9 required reoperation compared to 12 in the non-TDT group. In the TDT group, 76.74% of the patients were able to restore intestinal continuity, whereas only 40% of the patients in the non-TDT group achieved restored intestinal continuity. In the TDT group, 48.48% of patients developed LAR syndrome (LARS), whereas in the non-TDT group, 90% of patients developed LARS. The median drainage time was 7 days, the median postoperative hospital stay was 21 days, the median fasting time was 6.5 days, and the median hospitalization cost was 109205.93 RMB.

CONCLUSION: TDT use lowered reoperation rate but did not increase hospitalization expenses. After ≥ 1 year of follow-up, its use improved intestinal patency rate and reduced the incidence of LARS.}, } @article {pmid40290679, year = {2025}, author = {Li, ZY and Li, T and Cai, HQ}, title = {Overview of serrated polyposis syndrome from pathophysiology, diagnosis, and management.}, journal = {World journal of clinical oncology}, volume = {16}, number = {4}, pages = {103343}, pmid = {40290679}, issn = {2218-4333}, abstract = {This editorial discusses Thompson et al's original article, which is published in the most recent edition of the World Journal of Clinical Oncology and sheds critical light on the intertwined issues of health anxiety and work loss in individuals diagnosed with serrated polyposis syndrome (SPS). SPS is rare, characterized by the development of multiple serrated colorectal polyps. This editorial provides an overview of SPS, including its pathophysiology, clinical presentation, diagnostic criteria, management strategies, and the psychosocial impact. SPS is linked to molecular alterations, which drive carcinogenesis. Colonoscopy and histological analysis are used for diagnosis. Genetic testing is also considered where there is a family history. Quality of life can be greatly impacted by the psychosocial effects of SPS, especially health anxiety. Further understanding of the molecular mechanisms and creating individualized surveillance are required.}, } @article {pmid40290120, year = {2025}, author = {Hong, Y and Song, Y and Wang, W and Shi, J and Chen, X}, title = {Mitochondrial DNA editing: Key to the treatment of neurodegenerative diseases.}, journal = {Genes & diseases}, volume = {12}, number = {4}, pages = {101437}, pmid = {40290120}, issn = {2352-3042}, abstract = {Neuronal death is associated with mitochondrial dysfunction caused by mutations in mitochondrial DNA. Mitochondrial DNA becomes damaged when processes such as replication, repair, and nucleotide synthesis are compromised. This extensive accumulation of damaged mitochondrial DNA subsequently disrupts the normal function of mitochondria, leading to aging, degeneration, or even death of neurons. Mitochondrial dysfunction stands as a pivotal factor in the development of neurodegenerative diseases, including Parkinson's disease, Alzheimer's disease, Huntington's disease, and amyotrophic lateral sclerosis. Recognizing the intricate nature of their pathogenesis, there is an urgent need for more effective therapeutic interventions. In recent years, mitochondrial DNA editing tools such as zinc finger nucleases, double-stranded DNA deaminase toxin A-derived cytosine base editors, and transcription activator-like effector ligand deaminases have emerged. Their emergence will revolutionize the research and treatment of mitochondrial diseases. In this review, we summarize the advancements in mitochondrial base editing technology and anticipate its utilization in neurodegenerative diseases, offering insights that may inform preventive strategies and therapeutic interventions for disease phenotypes.}, } @article {pmid40289884, year = {2025}, author = {Janelidze, S and Ashton, NJ and Orduña Dolado, A and Nordström, U and Bali, D and Forsberg, KME and Keskin, I and Mastrangelo, A and Vacchiano, V and Liguori, R and Blennow, K and Zetterberg, H and Mattsson-Carlgren, N and Gonzalez-Ortiz, F and Parchi, P and Andersen, PM and Hansson, O}, title = {A comparison of p-tau assays for the specificity to detect tau changes in Alzheimer's disease.}, journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association}, volume = {21}, number = {4}, pages = {e70208}, pmid = {40289884}, issn = {1552-5279}, mesh = {Humans ; *tau Proteins/blood/cerebrospinal fluid ; *Alzheimer Disease/cerebrospinal fluid/blood/diagnosis ; Female ; Male ; *Amyotrophic Lateral Sclerosis/cerebrospinal fluid/blood/diagnosis ; Aged ; Sensitivity and Specificity ; Middle Aged ; Biomarkers/blood/cerebrospinal fluid ; Aged, 80 and over ; Immunoassay ; Phosphorylation ; }, abstract = {INTRODUCTION: We evaluated differences in p-tau levels between Alzheimer's disease (AD), a condition with brain-specific changes in p-tau, and amyotrophic lateral sclerosis (ALS), a condition associated with increases in peripheral p-tau levels.

METHODS: Cerebrospinal fluid and plasma from 668 participants were analyzed using immunoassays specific for the low-molecular-weight (LMW) tau isoforms present in the brain (i.e., p-tau217Lilly, p-tau181Lilly) and those that detect both LMW- and high-molecular-weight (HMW) tau expressed in the peripheral nervous system (i.e., p-tau217AlzPath, p-tau181UGOT).

RESULTS: Increases in plasma p-tau in ALS versus controls were significantly smaller for the LMW-specific p-tau assays (15.9%-20.5%) compared with non-specific assays (92.0%-121.3%). The LMW-specific p-tau assays showed significantly larger plasma p-tau increases in AD versus ALS, discriminating AD from ALS with areas under the curve (AUCs; 0.890.93) higher than the AUCs of the non-specific assays (0.54-0.74).

DISCUSSION: LMW-specific p-tau assays could be more useful in the diagnostic workup of AD, especially in population-based communities where conditions causing peripheral neuropathy are frequent.

HIGHLIGHTS: Increases in plasma phosphorylated tau (p-tau) in amyotrophic lateral sclerosis (ALS) versus controls were significantly smaller for low-molecular-weight (LMW)-specific p-tau assays (i.e., p-tau217Lilly, p-tau181Lilly) compared with p-tau assays that also detect high-molecular-weight (HMW) assays (i.e., p-tau217AlzPath, p-tau181UGOT). The LMW-specific p-tau assays showed significantly larger increases in plasma p-tau in AD versus ALS compared with the non-specific assays. The LMW-specific p-tau assays discriminated AD from ALS with higher precision, showing significantly better performance than the non-specific assays. LMW-specific p-tau assays could be more useful in the diagnostic workup of AD, especially in population-based communities where conditions causing peripheral neuropathy (such as ALS) are frequent.}, } @article {pmid40289140, year = {2025}, author = {Meyer, T and Boentert, M and Großkreutz, J and Weydt, P and Bernsen, S and Reilich, P and Steinbach, R and Rödiger, A and Wolf, J and Weyen, U and Ludolph, AC and Weishaupt, J and Petri, S and Lingor, P and Günther, R and Löscher, W and Weber, M and Münch, C and Maier, A and Grehl, T}, title = {Motor phenotypes of amyotrophic lateral sclerosis - a three-determinant anatomical classification based on the region of onset, propagation of motor symptoms, and the degree of upper and lower motor neuron dysfunction.}, journal = {Neurological research and practice}, volume = {7}, number = {1}, pages = {27}, pmid = {40289140}, issn = {2524-3489}, abstract = {BACKGROUND: In amyotrophic lateral sclerosis (ALS), heterogeneity of motor phenotypes is a fundamental hallmark of the disease. Distinct ALS phenotypes were associated with a different progression and survival. Despite its relevance for clinical practice and research, there is no broader consensus on the classification of ALS phenotypes.

METHODS: An expert consensus process for the classification of ALS motor phenotypes was performed from May 2023 to December 2024. A three-determinant anatomical classification was proposed which is based on the (1) region of onset (O), (2) the propagation of motor symptoms (P), and (3) the degree of upper (UMN) and/or lower motor neuron (LMN) dysfunction (M). Accordingly, this classification is referred to as the "OPM classification".

RESULTS: Onset phenotypes differentiate the site of first motor symptoms: O1) head onset; O2d) distal arm onset; O2p) proximal arm onset; O3r) trunk respiratory onset; O3a) trunk axial onset; O4d) distal leg onset; O4p) proximal leg onset. Propagation phenotypes differentiate the temporal propagation of motor symptoms from the site of onset to another, vertically distant body region: PE) earlier propagation (within 12 months of symptom onset); PL) later propagation (without propagation within 12 months of symptom onset), including the established phenotypes of "progressive bulbar paralysis" (O1, PL), "flail-arm syndrome" (O2p, PL), and "flail-leg syndrome" (O4d, PL); PN) propagation not yet classifiable as time since symptom onset is less than 12 months. Phenotypes of motor neuron dysfunction differentiate the degree of UMN and/or LMN dysfunction: M0) balanced UMN and LMN dysfunction; M1d) dominant UMN dysfunction; M1p) pure UMN dysfunction ("primary lateral sclerosis", PLS); M2d) dominant LMN dysfunction; M2p) pure LMN dysfunction ("progressive muscle atrophy", PMA); M3) dissociated motor neuron dysfunction with dominant LMN and UMN dysfunction of the arms and legs ("brachial amyotrophic spastic paraparesis"), respectively.

CONCLUSION: This consensus process aimed to standardize the clinical description of ALS motor phenotypes in clinical practice and research - based on the onset region, propagation pattern, and motor neuron dysfunction. This "OPM classification" contributes to specifying the prognosis, to defining the inclusion or stratification criteria in clinical trials and to correlate phenotypes with the underlying disease mechanisms of ALS.}, } @article {pmid40288877, year = {2025}, author = {Alcaraz, MR and Montemurro, M and Pisano, PL and Lombardi, JM and Bortolato, SA}, title = {Functional data analysis, a comprehensive framework for processing non-quadrilinear and low-selective data provided by four-way liquid chromatography analysis.}, journal = {Analytica chimica acta}, volume = {1356}, number = {}, pages = {344044}, doi = {10.1016/j.aca.2025.344044}, pmid = {40288877}, issn = {1873-4324}, abstract = {The chemometric treatment of higher-order chromatographic (LC) data often crashes due to two main effects: the chromatographic band shifts/warpings across samples and quasi-full overlaps between component signals, affecting their analytical selectivities. From a chemometric point of view, these phenomena have independent effects, although they can jointly contribute to the failure of the algorithms: 1) data multilinearity breaking, leading to the poor performance of multilinear decomposition algorithms, and 2) linear dependence between the analytes signals, causing the failure of folded models. Under this scenario, making chemometric processing feasible involves defining specific experimental conditions that minimize these effects or increasing the number of instrumental ways to deal with selectivity lost. This work presents the Functional Aligned of Pure Vectors (FAPV) algorithm for restoring four-way chromatographic data multilinearity and bearing the spectral overlap trouble. Simulated and experimental four-way data were used to test the FAPV analytical efficiency, covering a wide range of chromatographic artifacts. Based on a multi-injection procedure, the experimental case implied the chromatographic determination of two analytes with uncalibrated interferents in aqueous samples. Both data systems were subjected to FAPV and then processed by PARAFAC. Therefore, a comprehensive comparison was made with the most widely used chemometric models for non-multilinear chromatographic data (MCR-ALS and PARAFAC2). Moreover, the performance of the FAPV approach was compared with commonly used alignment procedures, e.g., correlation-optimized warping. The results (c.a. REPs of 10 % in both analytes from the experimental case) show the efficiency of the FAPV algorithm in solving the troubles observed in chromatographic/spectral data.}, } @article {pmid40288591, year = {2025}, author = {Servi, R and Akkoç, RF and Aksu, F and Servi, S}, title = {Therapeutic potential of enzymes, neurosteroids, and synthetic steroids in neurodegenerative disorders: A critical review.}, journal = {The Journal of steroid biochemistry and molecular biology}, volume = {251}, number = {}, pages = {106766}, doi = {10.1016/j.jsbmb.2025.106766}, pmid = {40288591}, issn = {1879-1220}, mesh = {Humans ; *Neurosteroids/therapeutic use/pharmacology ; *Neurodegenerative Diseases/drug therapy/metabolism ; Animals ; *Steroids/therapeutic use ; *Neuroprotective Agents/therapeutic use/pharmacology ; Alzheimer Disease/drug therapy/metabolism ; }, abstract = {Neurodegenerative disorders present a significant challenge to healthcare systems, mainly due to the limited availability of effective treatment options to halt or reverse disease progression. Endogenous steroids synthesized in the central nervous system, such as pregnenolone (PREG), dehydroepiandrosterone (DHEA), progesterone (PROG), and allopregnanolone (ALLO), have been identified as potential therapeutic agents for neurodegenerative diseases. Neurosteroids such as ALLO, DHEA, and PROG, as well as their synthetic analogs like Ganaxolene, Fluasterone, and Olexoxime, offer promising effects for conditions such as Alzheimer's disease (AD) and depression. Moreover, Brexanolone and Ganaxolone are synthetic steroids approved for the treatment of postpartum depression and epilepsy, respectively. Neurosteroids such as ALLO are crucial in modulating GABAergic neurotransmission and reducing neuroinflammation. These compounds enhance the activity of GABA-A receptors, leading to increased inhibitory signaling in the brain, which can help regulate mood, cognition, and neuroprotection. Small clinical trials and observational studies indicate that ALLO may have cognitive benefits, but no large-scale, definitive meta-analysis confirms a 20 % improvement in AD patients. Mitochondrial dysfunction plays a vital role in the pathogenesis of numerous neurological diseases due to the high-energy demand and sensitivity of neurons to oxidative stress. Reduced mitochondrial function leads to amyloid-beta plaques and tau tangles accumulation in AD. In Parkinson's disease (PD), mitochondrial dysfunction resulting from the PINK1 or Parkin genes leads to energy deficiencies and the accumulation of toxic byproducts. Mutations in genes such as SOD1, C9orf72, and TDP-43 have been associated with mitochondrial dysfunction in amyotrophic lateral sclerosis (ALS). Moreover, studies on these neurodegenerative diseases suggest that inflammation is not merely a consequence of neurodegeneration but is also an essential factor in this process. Many neurological disorders involve multifaceted interactions between genetics, the environment, and immune responses, making it difficult to pinpoint their exact causes. Future research aims to overcome these hurdles through genetic advances, regenerative medicine, and personalized therapies. Cutting-edge technologies such as artificial intelligence and high-throughput screening are expected to accelerate drug discovery and improve diagnostic accuracy. Increasing collaboration between interdisciplinary fields such as bioinformatics, neuroscience, and immunology will lead to innovative treatment strategies. This comprehensive review discusses the therapeutic effects of enzymes, neurosteroids, and synthetic steroids in different neurodegenerative diseases, particularly AD, PD, ALS, and MS. Potential challenges in the therapeutic use of neurosteroids, such as the limited bioavailability and off-target effects of synthetic steroids, are also discussed, and an up-to-date and comprehensive review of the impact of these steroids on neurodegenerative disorders is presented.}, } @article {pmid40288540, year = {2025}, author = {He, M and Jia, H}, title = {Enhancing access to scalp cooling therapy: How can we move forward? A response to Novice et al's "the financial burden of scalp cooling therapy: A nonprofit organization data analysis".}, journal = {Journal of the American Academy of Dermatology}, volume = {93}, number = {2}, pages = {e81}, doi = {10.1016/j.jaad.2025.03.093}, pmid = {40288540}, issn = {1097-6787}, } @article {pmid40287755, year = {2025}, author = {Vizziello, M and Dellarole, IL and Ciullini, A and Pascuzzo, R and Lombardo, A and Bellandi, F and Celauro, L and Battipaglia, C and Ciusani, E and Rizzo, A and Catania, M and Devigili, G and Della Seta, SA and Margiotta, V and Consonni, M and Faltracco, V and Tiraboschi, P and Riva, N and Portaleone, SMS and Zanusso, G and Legname, G and Lauria, G and Dalla Bella, E and Moda, F}, title = {TDP-43 seeding activity in the olfactory mucosa of patients with amyotrophic lateral sclerosis.}, journal = {Molecular neurodegeneration}, volume = {20}, number = {1}, pages = {49}, pmid = {40287755}, issn = {1750-1326}, support = {GR-2021-12372019//Ministero della Salute/ ; PNRR-MAD-2022-12376035//Ministero della Salute/ ; 5M-2018-23680266//Ministero della Salute/ ; RC//Ministero della Salute/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism/genetics/pathology ; *DNA-Binding Proteins/metabolism ; Male ; Female ; Middle Aged ; Aged ; *Olfactory Mucosa/metabolism/pathology ; Frontotemporal Dementia/metabolism ; Adult ; }, abstract = {BACKGROUND: In recent years, the seed amplification assay (SAA) has enabled the identification of pathological TDP-43 in the cerebrospinal fluid (CSF) and olfactory mucosa (OM) of patients with genetic forms of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). Here, we investigated the seeding activity of TDP-43 in OM samples collected from patients with sporadic ALS.

METHODS: OM samples were collected from patients with (a) sporadic motor neuron diseases (MND), including spinal ALS (n = 35), bulbar ALS (n = 18), primary lateral sclerosis (n = 10), and facial onset sensory and motor neuronopathy (n = 2); (b) genetic MND, including carriers of C9orf72[exp] (n = 6), TARDBP (n = 4), SQSTM1 (n = 3), C9orf72[exp] + SQSTM1 (n = 1), OPTN (n = 1), GLE1 (n = 1), FUS (n = 1) and SOD1 (n = 4) mutations; (c) other neurodegenerative disorders (OND), including Alzheimer's disease (n = 3), dementia with Lewy bodies (n = 8) and multiple system atrophy (n = 6); and (d) control subjects (n = 22). All samples were subjected to SAA analysis for TDP-43 (TDP-43_SAA). Plasmatic levels of TDP-43 and neurofilament-light chain (NfL) were also assessed in a selected number of patients.

RESULTS: TDP-43_SAA was positive in 29/65 patients with sporadic MND, 9/21 patients with genetic MND, 6/17 OND patients and 3/22 controls. Surprisingly, one presymptomatic individual also tested positive. As expected, OM of genetic non-TDP-43-related MND tested negative. Interestingly, fluorescence values from non-MND samples that tested positive were consistently and significantly lower than those obtained with sporadic and genetic MND. Furthermore, among TDP-43-positive samples, the lag phase observed in MND patients was significantly longer than that in non-MND patients. Plasma TDP-43 levels were significantly higher in sporadic MND patients compared to controls and decreased as the disease progressed. Similarly, plasma NfL levels were higher in both sporadic and genetic MND patients and positively correlated with disease progression rate (ΔFS). No significant correlations were detected between TDP-43_SAA findings and the biological, clinical, or neuropsychological parameters considered.

CONCLUSIONS: The OM of a subset of patients with sporadic MND can trigger seeding activity for TDP-43, as previously observed in genetic MND. Thus, TDP-43_SAA analysis of OM can improve the clinical characterization of ALS across different phenotypes and enhance our understanding of these diseases. Finally, plasma TDP-43 could serve as a potential biomarker for monitoring disease progression. However, further research is needed to confirm and expand these findings.}, } @article {pmid40287045, year = {2025}, author = {Dudzisz, K and Wandzik, I}, title = {Antisense oligonucleotides: A promising advancement in neurodegenerative disease treatment.}, journal = {European journal of pharmacology}, volume = {999}, number = {}, pages = {177644}, doi = {10.1016/j.ejphar.2025.177644}, pmid = {40287045}, issn = {1879-0712}, mesh = {Humans ; *Oligonucleotides, Antisense/therapeutic use ; *Neurodegenerative Diseases/genetics/drug therapy/therapy ; Animals ; Clinical Trials as Topic ; }, abstract = {Antisense oligonucleotides (ASOs) are a class of therapeutics designed to modulate gene expression and have shown promise in the treatment of various neurodegenerative diseases. As of March 2025, four ASO-based therapies have received approval for the treatment of neurodegenerative diseases, including spinal muscular atrophy (SMA), amyotrophic lateral sclerosis (ALS), and hereditary transthyretin amyloidosis (ATTR). These approvals underscore the therapeutic potential of ASOs as effective treatments for neurodegenerative diseases by addressing specific genetic abnormalities. This is best demonstrated by clinical studies in more than a dozen ASOs, which could pave the way for the development of new therapeutics soon. Moreover, the ongoing extended clinical studies, which target presymptomatic carriers, have significant potential to cure familial ALS based on the SOD1 gene mutation. This review provides an update on clinical trials, highlighting promising results and the challenges encountered.}, } @article {pmid40286820, year = {2025}, author = {Cepica, TB and Xie, L and Faden, DF and Stone, CJ and Feng, R and Werth, VP and Chong, BF}, title = {Regarding Wu et al's "response to Cepica et al's 'smoking status is a negative predictor of 6-month cutaneous lupus activity trends: A prospective cohort study'".}, journal = {Journal of the American Academy of Dermatology}, volume = {93}, number = {2}, pages = {e89-e90}, doi = {10.1016/j.jaad.2025.04.050}, pmid = {40286820}, issn = {1097-6787}, } @article {pmid40286795, year = {2025}, author = {Murdock, BJ and Zhao, B and Webber-Davis, IF and Teener, SJ and Pawlowski, KD and Famie, JP and Piecuch, CE and Jang, DG and Feldman, EL and Zhao, L and Goutman, SA}, title = {Early immune system changes in amyotrophic lateral sclerosis correlate with later disease progression.}, journal = {Med (New York, N.Y.)}, volume = {6}, number = {8}, pages = {100673}, pmid = {40286795}, issn = {2666-6340}, support = {R01 NS120926/NS/NINDS NIH HHS/United States ; R01 TS000339/TS/ATSDR CDC HHS/United States ; }, mesh = {*Amyotrophic Lateral Sclerosis/blood/diagnosis/immunology ; Disease Progression ; Case-Control Studies ; Biomarkers/blood ; Flow Cytometry ; Longitudinal Studies ; *Immunity, Cellular ; Humans ; Male ; Female ; Middle Aged ; Aged ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disease with no cure and limited treatment options. The immune system is implicated in disease pathology, unlocking a potential therapeutic avenue. However, it is unclear whether immune changes are a cause or consequence of disease progression.

METHODS: Peripheral immune cells were longitudinally measured at monthly intervals in 55 ALS and 50 control participants. 22 peripheral immune markers in the blood were assessed using flow cytometry, and clinical progression was assessed using the revised ALS functional rating scale (ALSFRS-R). Individual immune markers, their trajectories, and overall variability were compared in ALS versus control participants; ALS participants were also stratified by clinical progression rates and assessed similarly across progression groups. Finally, a novel, lagged linear regression model correlated the rate of immune changes to subsequent downstream ALSFRS-R changes.

FINDINGS: Numerous immune markers were dysregulated in ALS versus control participants, with altered levels, trajectories, or variability in immune populations and surface markers. ALS participants had increased immune variability relative to control participants; within ALS participants, faster progressors overall had decreased marker variability. Finally, natural killer (NK) cell numbers, NK cell subpopulations, and NK cell surface markers were significantly associated with downstream ALS progression.

CONCLUSIONS: The immune system is dysregulated in ALS and more consistently dysregulated in faster ALS progression, and immune dysregulation occurs upstream of clinical changes. These findings suggest that the immune system is a causal factor of ALS progression in human patients.

FUNDING: CReATe Consortium, NIH, Target ALS, DoD, ALSA.}, } @article {pmid40285687, year = {2025}, author = {Altemus, JJ and Lay, MA and Thompson, VF and Schwartz, JC}, title = {Purification of Low-Complexity Domain Proteins FUS, EWSR1, and Their Fusions.}, journal = {Current protocols}, volume = {5}, number = {4}, pages = {e70136}, pmid = {40285687}, issn = {2691-1299}, mesh = {*RNA-Binding Protein FUS/isolation & purification/chemistry/genetics/metabolism ; *RNA-Binding Protein EWS/isolation & purification/chemistry/genetics/metabolism ; Humans ; *Oncogene Proteins, Fusion/isolation & purification/chemistry ; Protein Domains ; }, abstract = {FET proteins are large multifunctional proteins that have several key roles in biology. The FET family of proteins, including FUS, EWSR1, and TAF15, play critical roles in transcription regulation, RNA processing, and DNA damage repair. These multifunctional RNA- and DNA-binding proteins are ubiquitously expressed and conserved across vertebrate species. They contain low-complexity (LC) domains that allow them to assemble and phase separate but also makes the proteins prone to aggregation. Aberrations in FET proteins, such as point mutations, aggregation, or translocations leading to fusion proteins, have been implicated in several pathologies, including frontotemporal lobar degeneration (FTLD), amyotrophic lateral sclerosis (ALS), and Ewing sarcoma. In vitro study of FET proteins is hampered by their propensity to aggregate, their disordered structure, and their susceptibility to proteolysis, making high-yield production difficult. Here, we present optimized methods for the purification of full-length FUS, EWSR1, and their fusion proteins. These protocols enable researchers to overcome issues related to aggregation and solubility, facilitating biochemical and biophysical studies of these critical yet complex proteins. © 2025 The Author(s). Current Protocols published by Wiley Periodicals LLC. Basic Protocol: Purification of EWSR1 and FUS proteins Alternate Protocol: Purification for fusion proteins.}, } @article {pmid40285624, year = {2025}, author = {Vasta, R and Koumantakis, E and Canosa, A and Manera, U and Grassano, M and Palumbo, F and Cabras, S and Matteoni, E and Di Pede, F and De Mattei, F and Vergnano, F and Mandrioli, J and Simonini, C and Martinelli, I and De Marchi, F and Mazzini, L and Moglia, C and Calvo, A and Chiò, A}, title = {Phosphatemia is an Independent Prognostic Factor in Amyotrophic Lateral Sclerosis.}, journal = {Annals of neurology}, volume = {98}, number = {2}, pages = {286-293}, pmid = {40285624}, issn = {1531-8249}, support = {2017SNW5MB//Ministero dell'Istruzione, dell'Università e della Ricerca/ ; 259867//European Commission's Health Seventh Framework Programme/ ; 101137074//European Union's Horizon 2020 research and innovation programme/ ; GA101017598//European Union's Horizon 2020 research and innovation programme/ ; PNRR-MAD-2022-12375731//Ministero della Salute/ ; RF-2016-02362405//Ministero della Salute/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/blood/diagnosis/mortality ; Male ; Female ; Middle Aged ; Prognosis ; Aged ; Biomarkers/blood ; Creatinine/blood ; *Hyperphosphatemia/blood/diagnosis ; Adult ; *Phosphates/blood ; Phosphorus/blood ; }, abstract = {OBJECTIVE: The objective of this study was to evaluate the prognostic value of several muscle damage biomarkers.

METHODS: Data from Piemonte and Valle d'Aosta Amyotrophic Lateral Sclerosis (PARALS) were considered for this study. Survival was defined as the time from diagnosis to death, tracheostomy, or the censoring date. Blood levels of potassium, creatinine, creatine kinase, phosphorus, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) diagnosis were evaluated as potential prognostic biomarkers. A Cox model was developed for each biomarker and adjusted for sex, onset age, onset site, and diagnostic delay. Significant findings from PARALS were evaluated in the Pooled Resource Open-Access Amyotrophic Lateral Sclerosis Clinical Trials (PRO-ACT) database. Additionally, a joint model was constructed to evaluate the prognostic role of phosphatemia slope over time using longitudinal data from PRO-ACT.

RESULTS: A total of 1,444 and 1,023 patients were included in the PARALS and PRO-ACT cohorts, respectively. Only creatinine (hazard ratio [HR] = 0.65, 95% confidence interval [CI] = 0.50-0.85) and phosphorus (HR = 1.14, 95% CI = 1.04-1.24) showed a significant association with survival in the PARALS cohort. These findings were further validated in the PRO-ACT cohort (creatinine HR = 0.21, 95% CI = 0.13-0.35, p < 0.0001; phosphorus HR = 2.35, 95% CI = 1.13-4.88, p = 0.02). Longitudinal data from the PRO-ACT database showed that an increase of 0.1 mmol/l per month in phosphate levels was also associated with a HR of 8.26 (95% CI = 1.07-96.6, p = 0.044).

INTERPRETATION: Creatininemia was confirmed as a prognostic marker in amyotrophic lateral sclerosis (ALS). Additionally, both phosphatemia levels at diagnosis and its rate of change over time were identified as a potential prognostic marker for ALS. As with other blood biomarkers, phosphate levels are cost-effective and minimally invasive to measure, supporting their potential use in clinical trials. ANN NEUROL 2025;98:286-293.}, } @article {pmid40285121, year = {2025}, author = {Chatragadda, L and Fletcher, A and Zhong, S and Vargas, FA and Bhagat, N and Mankodiya, K and Delmonico, MJ and Solanki, D}, title = {Development and Assessment of a Soft Wearable for sEMG-Based Hand Grip Detection and Control of a Virtual Environment.}, journal = {Sensors (Basel, Switzerland)}, volume = {25}, number = {8}, pages = {}, pmid = {40285121}, issn = {1424-8220}, support = {N/A//Office of Undergraduate Research and Innovation, University of Rhode Island/ ; }, mesh = {Humans ; *Electromyography/methods/instrumentation ; *Hand Strength/physiology ; *Wearable Electronic Devices ; Male ; Female ; Middle Aged ; Adult ; Neurodegenerative Diseases/physiopathology ; Aged ; Hand/physiology ; Feasibility Studies ; }, abstract = {BACKGROUND: As the number of individuals diagnosed with neurodegenerative disorders (NDs) rises, there is a growing need to enhance both the quantity and quality of approaches used to treat these debilitating conditions. The progression of NDs can cause muscle weakness in the lower or upper limbs. We particularly focus on the area of the upper limb, specifically grip rehabilitation, by developing a system (VRGrip) that can reliably record electromyography (EMG) events of the hand flexor muscles to control an adaptive and engaging game using grip exertion. The purpose of this study was to determine the feasibility of using the VRGrip system.

METHODS: We prototyped a three-component wearable system consisting of an e-textile forearm band (E-band), data acquisition module (DAM), and a computer game. This allows participants to play a game by squeezing their dominant hand. A feasibility study was completed with 9 individuals who self-reported an ND (including Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), Charcot-Marie-Tooth disease (CMT), spinal muscular atrophy (SMA), and essential tremor (ET)) and 12 individuals who self-reported to be relatively healthy (RH). Each participant completed 15 min of gameplay (three trials of five minutes), where they would squeeze a resistive ball to trigger in-game actions. The user experience was then evaluated via a User Satisfaction Evaluation Questionnaire (USEQ; scored 0-30, with 30 being best).

RESULTS: Analysis of the grip detection reliability during the feasibility study resulted in an F1 score of 0.8343 ± 0.1208 for the healthy participant group and 0.8401 ± 0.1034 for the ND participant group. The USEQ (Avg. score: 4.65 ± 0.51) indicated that participants found the system comfortable, engaging, and enjoyable. Additionally, we potentially identified age-related changes in muscle fatigue.

CONCLUSION: The results of this study demonstrate that our VRGrip system could be used for hand grip detection in a virtual environment. In the future, we aim to conduct longitudinal studies to determine if repeated use of the system has merit for grip rehabilitation.}, } @article {pmid40284554, year = {2025}, author = {Tamai, R and Kiyoura, Y}, title = {Candida Infections: The Role of Saliva in Oral Health-A Narrative Review.}, journal = {Microorganisms}, volume = {13}, number = {4}, pages = {}, pmid = {40284554}, issn = {2076-2607}, support = {21K10233, 23K09511//KAKEN/ ; }, abstract = {Candida species, particularly Candida albicans, are causative agents of oral infections to which immunocompromised patients are especially susceptible. Reduced saliva flow (xerostomia) can lead to Candida overgrowth, as saliva contains antibacterial components such as histatins and β-defensins that inhibit fungal growth and adhesion to the oral mucosa. Candida adheres to host tissues, forms biofilms, and secretes enzymes required for tissue invasion and immune evasion. Secretory asparaginyl proteinases (Saps) and candidalysin, a cytolytic peptide toxin, are vital to Candida virulence, and agglutinin-like sequence (Als) proteins are crucial for adhesion, invasion, and biofilm formation. C. albicans is a risk factor for dental caries and may increase periodontal disease virulence when it coexists with Porphyromonas gingivalis. Candida infections have been suggested to heighten the risk of oral cancer based on a relationship between Candida species and oral squamous cell carcinoma (OSCC) or oral potentially malignant disorder (OPMD). Meanwhile, β-glucan in the Candida cell wall has antitumor effects. In addition, Candida biofilms protect viruses such as herpesviruses and coxsackieviruses. Understanding the intricate interactions between Candida species, host immune responses, and coexisting microbial communities is essential for developing preventive and therapeutic strategies against oral Candida infections, particularly in immunocompromised individuals.}, } @article {pmid40284406, year = {2025}, author = {Ansari, UA and Srivastava, A and Srivastava, AK and Pandeya, A and Vatsa, P and Negi, R and Singh, A and Pant, AB}, title = {Targeting TDP-43 Proteinopathy in hiPSC-Derived Mutated hNPCs with Mitoxantrone Drugs and miRNAs.}, journal = {Pharmaceutics}, volume = {17}, number = {4}, pages = {}, pmid = {40284406}, issn = {1999-4923}, support = {5/4-5/3/9/DHR/Neuro/2021-NCD-1//Indian Council of Medical Research/ ; }, abstract = {Background/Objectives: TDP-43 mutation-driven Amyotrophic Lateral Sclerosis (ALS) motor neuron disease is one of the most prominent forms (approximately 97%) in cases of sporadic ALS. Dysfunctional autophagy and lysosomal function are the prime mechanisms behind ALS. Mitoxantrone (Mito), a synthetic doxorubicin analog, is an inhibitor of DNA and RNA synthesis/repair via intercalating with nitrogenous bases and inhibiting topoisomerase II. The therapeutic potential of miRNAs associated with disease conditions has also been reported. This study explores the therapeutic potential of Mito along with miRNAs against mutated TDP-43 protein-induced proteinopathy in human-induced pluripotent stem cell (hiPSC)-derived human neural progenitor cells (hNPCs). Methods: HiPSCs mutated for TDP-43 were differentiated into hNPCs and used to explore the therapeutic potential of Mito at a concentration of 1 μM for 24 h (the identified non-cytotoxic dose). The therapeutic effects of Mito on miRNA expression and various cellular parameters such as mitochondrial dynamics, autophagy, and stress granules were assessed using the high-throughput Open Array technique, immunocytochemistry, flow cytometry, immunoblotting, and mitochondrial bioenergetic assay. Results: Mutated TDP-43 protein accumulation causes stress granule formation (G3BP1), mitochondrial bioenergetic dysfunction, SOD1 accumulation, hyperactivated autophagy, and ER stress in hNPCs. The mutated hNPCs also show dysregulation in six miRNAs (miR-543, miR-34a, miR-200c, miR-22, miR-29b, and miR-29c) in mutated hNPCs. A significant restoration of TDP-43 mutation-induced alterations could be witnessed upon the exposure of mutated hNPCs to Mito. Conclusions: Our study indicates that miR-543, miR-29b, miR-22, miR-200c, and miR-34a have antisense therapeutic potential alone and in combination with Mitoxantrone.}, } @article {pmid40284160, year = {2025}, author = {Fernandez-Pombo, A and Izquierdo, AG and Canton-Blanco, A and Garcia-Sobrino, T and Hervás, D and Martínez-Olmos, MA and Pardo, J and Crujeiras, AB}, title = {Blood DNA Methylation in Nuclear and Mitochondrial Sequences Links to Malnutrition and Poor Prognosis in ALS: A Longitudinal Study.}, journal = {Nutrients}, volume = {17}, number = {8}, pages = {}, pmid = {40284160}, issn = {2072-6643}, support = {CPII22/00008//Instituto de Salud Carlos III/ ; CIBEROBN//Instituto de Salud Carlos III/ ; IN607B-20240301//Xunta de Galicia/ ; CPII22/00008//Instituto de Salud Carlos III/ ; JR23/00042//Instituto de Salud Carlos III/ ; }, mesh = {Humans ; *DNA Methylation ; *Amyotrophic Lateral Sclerosis/genetics/complications/blood/mortality ; Male ; Female ; Middle Aged ; *Malnutrition/genetics/blood/complications ; Longitudinal Studies ; Aged ; Prognosis ; Disease Progression ; Nutritional Status ; Biomarkers/blood ; *DNA, Mitochondrial/blood/genetics ; Oxidative Stress ; Epigenesis, Genetic ; }, abstract = {Background: Malnutrition in amyotrophic lateral sclerosis (ALS) is associated with disease severity, and epigenetic regulation may be involved. The aim of this study was to assess the methylation levels of specific DNA sequences from the nuclear and mitochondrial genomes in a population with ALS to elucidate their relationship with nutritional status and the evolution of the disease. Methods: Patients with ALS were evaluated between 2013 and 2021 (n = 66). They were categorized according to their nutritional status, using the Global Leadership Initiative on Malnutrition (GLIM) criteria, and disease progression, using the ALS Functional Rating (ALSFRS-R) Scale. DNA samples were extracted from leukocytes at the time of diagnosis for analysis of DNA methylation levels of markers of oxidative stress, mitochondrial function and global methylation (D-loop, GSTP1, and LINE-1). Results: According to the GLIM criteria, 29 (43.9%) patients had malnutrition (22.7%-moderate; 21.2%-severe), which was positively correlated with ALS disease progression (r = 0.414; p < 0.01) and death (r = 0.687; p < 0.01). Mortality occurred in 43.9% of the patients (median time to death, 18.7 (1.7-82.7) months). A significant association was observed between DNA methylation levels of the D-loop, GSTP1, and the CpG1 site of LINE-1 and malnutrition, disease progression at diagnosis, and death. The D-loop was the best predictor of malnutrition (AUC, 0.79; p < 0.01), disease progression (AUC, 0.70; p < 0.01), and mortality (AUC, 0.71; p < 0.01). Conclusions: This study revealed, for the first time, the early detection of D-loop methylation levels as a potential biomarker of nutritional status in patients with ALS, which may be useful for personalized nutritional management aimed at counteracting disease progression.}, } @article {pmid40284157, year = {2025}, author = {Sousa-Catita, D and Mascarenhas, P and Oliveira, C and Grunho, M and Santos, CA and Cabrita, J and Correia, P and Fonseca, J}, title = {Nutrition and Survival of 150 Endoscopic Gastrostomy-Fed Patients with Amyotrophic Lateral Sclerosis.}, journal = {Nutrients}, volume = {17}, number = {8}, pages = {}, pmid = {40284157}, issn = {2072-6643}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/mortality/therapy/complications ; *Gastrostomy/methods/mortality ; Male ; Female ; Aged ; *Enteral Nutrition/methods/mortality ; *Nutritional Status ; Middle Aged ; Kaplan-Meier Estimate ; Aged, 80 and over ; }, abstract = {Background/Objectives: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder affecting motor neurons in the brain and spinal cord, leading to muscle weakness, atrophy, and paralysis. Treatment focuses on symptom management, using medication, physiotherapy, and nutritional support. In this context, endoscopic gastrostomy (PEG) can provide adequate feeding, hopefully improving nutrition and preventing complications. Methods: We studied ALS patients undergoing PEG over three months post-procedure, using anthropometry ((BMI)-body mass index; (MUAC)-mid-upper arm circumference; (TSF)-tricipital skinfold; (MAMC)-mid-arm muscle circumference) and laboratory data (Albumin; Transferrin; total cholesterol and hemoglobin), evaluating survival, complications, and nutritional/clinical status. Statistical analysis included Kaplan-Meier survival estimation and Cox regression to assess nutritional markers associated with survival. Results: 150 ALS patients underwent gastrostomy, mostly older adults (mean age: 66.1 years; median: 67). Mean survival was 527 [95% CI: 432-622] days, median 318 [95% CI: 236-400]. ALS bulbar subtype, MUAC and MAMC positively impacted PEG-feeding survival time (p < 0.05, Wald test). During the first three months of PEG feeding, each unit increase (cm) in MUAC and MAMC lowered death risk by 10% and 11%, respectively, highlighting the importance of nutrition care for survival. The bulbar subtype showed higher PEG feeding survival, with a 55.3% lower death hazard than the spinal subtype. There were no major PEG complications. Conclusions: ALS patients present a high risk of malnutrition. Patients that improved MAMC and MUAC in the first three PEG-fed months presented longer survival. Early PEG nutrition, even when some oral feeding is still possible, may reinforce the preventative role of enteral feeding in maintaining nutrition and potentially improving survival.}, } @article {pmid40283960, year = {2025}, author = {Salomon-Zimri, S and Kerem, N and Linares, GR and Russek-Blum, N and Ichida, JK and Tracik, F}, title = {Elucidating the Synergistic Effect of the PrimeC Combination for Amyotrophic Lateral Sclerosis in Human Induced Pluripotent Stem Cell-Derived Motor Neurons and Mouse Models.}, journal = {Pharmaceuticals (Basel, Switzerland)}, volume = {18}, number = {4}, pages = {}, pmid = {40283960}, issn = {1424-8247}, abstract = {Background: Amyotrophic lateral sclerosis (ALS) is a multifactorial neurodegenerative disease characterized by the involvement of multiple pathways and mechanisms. The complexity of its pathophysiology is reflected in the diverse hypotheses relating to its underlying causes. Given this intricate interplay of processes, a combination therapy approach offers a promising strategy. Combination therapies have demonstrated significant success in treating complex diseases, where they aim to achieve synergistic therapeutic effects and reduce drug dosage. PrimeC is an oral combination treatment composed of a patented novel formulation consisting of specific and unique doses of two well-characterized drugs (ciprofloxacin and celecoxib). It aims to synergistically inhibit the progression of ALS by addressing key elements of its pathophysiology. Objectives: Demonstrating the synergistic effect of the PrimeC combination compared to each of its individual components, celecoxib and ciprofloxacin, and assessing its ability to improve the drug concentration profile and efficacy. Methods: The efficacy of the PrimeC combination was assessed in a survival assay using human induced pluripotent stem cell (iPSC)-derived motor neurons. Additionally, a drug profiling study was conducted, measuring drug levels in the brain and serum of C57BL mice treated with a single compound versus the combination. Results: Motor neurons modeling ALS treated with the PrimeC combination exhibited better survival rates compared to treatment with either individual compound alone. The enhanced efficacy of the combination was further supported by a drug concentration profiling study in rodents, demonstrating that the PrimeC combination resulted in increased ciprofloxacin concentrations in both brain tissue and serum-highlighting the optimized interaction and synergistic potential of its two comprising agents. Conclusions: Our findings support the potential of combination therapy as an effective strategy for ALS treatment. Specifically, the PrimeC combination demonstrated promising therapeutic effects, providing a strong rationale for its ongoing development as a targeted treatment for ALS.}, } @article {pmid40283933, year = {2025}, author = {Martín-Ruiz, J and Maset-Roig, R and Caplliure-Llopis, J and Villarón-Casales, C and Alarcón-Jiménez, J and de Bernardo, N and Proaño, B and Menargues-Ramírez, R and Selvi-Sabater, P and de la Rubia-Ortí, JE}, title = {Enhanced Acute Muscle Activation in ALS Patients Following Liposomal Curcumin, Resveratrol, and Dutasteride Administration.}, journal = {Pharmaceuticals (Basel, Switzerland)}, volume = {18}, number = {4}, pages = {}, pmid = {40283933}, issn = {1424-8247}, abstract = {Introduction: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by loss of electrical activity and motor control at the muscular level. Therapeutic alternatives, such as the polyphenolic antioxidants curcumin and resveratrol in liposome form, or the drug dutasteride, could be effective for muscular activity. Objective: To measure the acute change in electrical muscle activation after administration of a combination of curcumin in liposomal form, resveratrol, and dutasteride in patients with ALS. Materials and methods: Patients with bulbar and spinal ALS were selected and randomly distributed into an intervention group (IG), which received an oral combination of curcumin in liposomal form/resveratrol[®] and dutasteride for 2 months, and a control group (CG), which received a placebo. Electrical activity to determine basal muscle activation and fasciculations was measured before and after the intervention using surface electromyography of the biceps brachii (BB), triceps brachii (TB), rectus femoris (RF), and tibialis anterior (TA). Within comparisons of pre and post-muscular variations in each group were conducted. Results: Electrical basal activity increased only for the IG in the right (p = 0.05; g = -0.45) and left (p = 0.004; g = -0.74) hemibody muscles and also presented less variation among them after treatment in the IG. For fasciculations, there was an increase in the total activation of the upper muscles in the IG (p = 0.017; g = -0.86) and for the lower muscles in the CG (p = 0.037; g = -0.68). The pattern of muscle activation remained constant in the IG but experienced variations in the CG.}, } @article {pmid40283578, year = {2025}, author = {Mantle, D and Hargreaves, I}, title = {Coenzyme Q10 and the Blood-Brain Barrier: An Overview.}, journal = {Journal of clinical medicine}, volume = {14}, number = {8}, pages = {}, pmid = {40283578}, issn = {2077-0383}, abstract = {Mitochondrial dysfunction is a common factor known to be involved in the pathogenesis of a number of neurological disorders, including Parkinson's disease, Alzheimer's disease, and amyotrophic lateral sclerosis. Given the importance of coenzyme Q10 (CoQ10) in promoting normal mitochondrial function, and the deficiency of CoQ10 reported in such neurological disorders, there is a rationale for investigating the potential therapeutic role of supplementary CoQ10. However, while there is evidence for the efficacy of CoQ10 supplementation in animal models of the above disorders, randomised controlled clinical trials supplementing CoQ10 in PD, AD, or ALS have had disappointing outcomes. This in turn may be a reflection of the current uncertainty as to whether CoQ10 can access the blood-brain barrier in human subjects. In an attempt to further elucidate the disparity in outcomes of such preclinical and clinical studies, in this article we have reviewed evidence from the peer-reviewed literature to establish the ability of CoQ10 to access the brain via the BBB.}, } @article {pmid40283201, year = {2025}, author = {González-Sánchez, M and Ramírez-Expósito, MJ and Martínez-Martos, JM}, title = {Pathophysiology, Clinical Heterogeneity, and Therapeutic Advances in Amyotrophic Lateral Sclerosis: A Comprehensive Review of Molecular Mechanisms, Diagnostic Challenges, and Multidisciplinary Management Strategies.}, journal = {Life (Basel, Switzerland)}, volume = {15}, number = {4}, pages = {}, pmid = {40283201}, issn = {2075-1729}, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder characterized by the progressive degeneration of upper and lower motor neurons, leading to muscle atrophy, paralysis, and respiratory failure. This comprehensive review synthesizes the current knowledge on ALS pathophysiology, clinical heterogeneity, diagnostic frameworks, and evolving therapeutic strategies. Mechanistically, ALS arises from complex interactions between genetic mutations (e.g., in C9orf72, SOD1, TARDBP (TDP-43), and FUS) and dysregulated cellular pathways, including impaired RNA metabolism, protein misfolding, nucleocytoplasmic transport defects, and prion-like propagation of toxic aggregates. Phenotypic heterogeneity, manifesting as bulbar-, spinal-, or respiratory-onset variants, complicates its early diagnosis, which thus necessitates the rigorous application of the revised El Escorial criteria and emerging biomarkers such as neurofilament light chain. Clinically, ALS intersects with frontotemporal dementia (FTD) in up to 50% of the cases, driven by shared TDP-43 pathology and C9orf72 hexanucleotide expansions. Epidemiological studies have revealed a lifetime risk of 1:350, with male predominance (1.5:1) and peak onset between 50 and 70 years. Disease progression varies widely, with a median survival of 2-4 years post-diagnosis, underscoring the urgency for early intervention. Approved therapies, including riluzole (glutamate modulation), edaravone (antioxidant), and tofersen (antisense oligonucleotide), offer modest survival benefits, while dextromethorphan/quinidine alleviates the pseudobulbar affect. Non-pharmacological treatment advances, such as non-invasive ventilation (NIV), prolong survival by 13 months and improve quality of life, particularly in bulb-involved patients. Multidisciplinary care-integrating physical therapy, respiratory support, nutritional management, and cognitive assessments-is critical to addressing motor and non-motor symptoms (e.g., dysphagia, spasticity, sleep disturbances). Emerging therapies show promise in preclinical models. However, challenges persist in translating genetic insights into universally effective treatments. Ethical considerations, including euthanasia and end-of-life decision-making, further highlight the need for patient-centered communication and palliative strategies.}, } @article {pmid40282367, year = {2025}, author = {Watanabe, Y and Nakagawa, T and Nakagawa, M and Nakayama, K}, title = {The Molecular Intersection of NEK1, C21ORF2, Cyclin F, and VCP in ALS Pathogenesis.}, journal = {Genes}, volume = {16}, number = {4}, pages = {}, pmid = {40282367}, issn = {2073-4425}, support = {23K06367//Japan Society for the Promotion of Science/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology ; *NIMA-Related Kinase 1/genetics/metabolism ; *Valosin Containing Protein/genetics/metabolism ; *Cyclins/genetics/metabolism ; DNA-Binding Proteins/genetics/metabolism ; Animals ; DNA Damage ; Mutation ; DNA Repair ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder characterized by the progressive degeneration of motor neurons, leading to muscle weakness, paralysis, and death. Although significant progress has been made in understanding ALS, its molecular mechanisms remain complex and multifactorial. This review explores the potential convergent mechanisms underlying ALS pathogenesis, focusing on the roles of key proteins including NEK1, C21ORF2, cyclin F, VCP, and TDP-43. Recent studies suggest that mutations in C21ORF2 lead to the stabilization of NEK1, while cyclin F mutations activate VCP, resulting in TDP-43 aggregation. TDP-43 aggregation, a hallmark of ALS, impairs RNA processing and protein transport, both of which are essential for neuronal function. Furthermore, TDP-43 has emerged as a key player in DNA damage repair, translocating to DNA damage sites and recruiting repair proteins. Given that NEK1, VCP, and cyclin F are also involved in DNA repair, this review examines how these proteins may intersect to disrupt DNA damage repair mechanisms, contributing to ALS progression. Impaired DNA repair and protein homeostasis are suggested to be central downstream mechanisms in ALS pathogenesis. Ultimately, understanding the interplay between these pathways could offer novel insights into ALS and provide potential therapeutic targets. This review aims to highlight the emerging connections between protein aggregation, DNA damage repair, and cellular dysfunction in ALS, fostering a deeper understanding of its molecular basis and potential avenues for intervention.}, } @article {pmid40282285, year = {2025}, author = {Hohman, G and Watson, A and Eldeeb, MA}, title = {A Novel Approach to Relocate Misplaced Proteins in Cells.}, journal = {Biology}, volume = {14}, number = {4}, pages = {}, pmid = {40282285}, issn = {2079-7737}, abstract = {Proper cellular function hinges on appropriate subcellular protein localization. When cellular proteins become mislocalized, they can accumulate, cause cellular damage, and disrupt many biochemical and cellular processes. Notably, mislocalized protein accumulation and the resulting cytotoxic effects are salient features of neurodegenerative diseases including Alzheimer's, Parkinson's disease, and ALS. The detrimental cellular consequences of mislocalized proteins accumulation make it crucial to develop techniques and approaches that counteract this malfunction. Remarkably, a recent study by Ng et al. introduced targeted relocalization-activating molecules (TRAMs) as a novel molecular tool for relocalizing endogenous target proteins to counteract disease-associated mislocalized proteins. The authors developed a quantitative single-cell analysis to evaluate the strength and relocalization capability of TRAMs by coupling a target protein and a shuttle protein. Herein, we briefly highlight and discuss the potential molecular implications for targeted protein relocalization as an effective approach for correcting mislocalized proteins.}, } @article {pmid40282131, year = {2025}, author = {Monteiro, A and Ali, AM and Laranjeira, C}, title = {Lived Experiences of Physiotherapists in Caring for People with Advanced Amyotrophic Lateral Sclerosis in Portugal: A Phenomenological Study.}, journal = {Behavioral sciences (Basel, Switzerland)}, volume = {15}, number = {4}, pages = {}, pmid = {40282131}, issn = {2076-328X}, support = {(UIDB/05704/2020 and UIDP/05704/2020)-and under the Scientific Employment Stimu-lus-Institutional Call (https://doi.org/10.54499/CEECINST/00051/2018/CP1566/CT0012, accessed on 1 March 2025).//Fundação para a Ciência e Tecnologia/ ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a disease that has a multidimensional impact on a person's life, with symptoms associated with a significant loss of autonomy. Specialized palliative care (PC) should be provided early and throughout the course of the disease. Indeed, physiotherapists should be understood as integral members of the multidisciplinary team in PC, in the care and improvement of the quality of life of these people. This study aimed to describe the lived experience of physiotherapists in the context of intervention in people with advanced ALS and their families. Descriptive phenomenology was employed as a framework for conducting semi-structured interviews to reveal experiences. Sixteen physiotherapists who performed interventions on at least one person with advanced ALS in the last 2 years were included in the study. The study involved conducting semi-structured individual interviews, through the Zoom[®] videoconferencing platform (version 6.4.3). Data were analyzed according to Giorgi's five-stage approach and managed using webQDA software (Version 3.0, University of Aveiro, Aveiro, Portugal). The COREQ checklist was applied in the study. Participants were mostly female (n = 12) and aged between 26 and 55 years (M = 36.81; SD = 6.75). Four constituents were identified: (1) undulating course of a complex disease; (2) barriers to person-centered care; (3) enablers of person-centered care; (4) transition between curative and palliative care. The findings illustrate the multidimensional impact of the disease trajectory on the person and their family. This study highlights the need to invest in specialized training for physiotherapists, contributing to a person-centered PC practice with an impact on promoting comfort and quality of life.}, } @article {pmid40281300, year = {2025}, author = {Upadhayay, S and Soni, D and Dhureja, M and Temgire, P and Kumar, V and Arthur, R and Kumar, P}, title = {Role of Fibroblast Growth Factors in Neurological Disorders: Insight into Therapeutic Approaches and Molecular Mechanisms.}, journal = {Molecular neurobiology}, volume = {}, number = {}, pages = {}, pmid = {40281300}, issn = {1559-1182}, abstract = {In the last few decades, the incidence and progression of neurological disorders have consistently increased, which mainly occur due to environmental pollution, genetic abnormalities, and modern lifestyles. Several case reports suggested that these factors enhanced oxidative stress, mitochondrial dysfunction, inflammation, and apoptosis, leading to neurological disease. The pathophysiology of neurological disorders is still not understood, mainly due to the diversity within affected populations. Existing treatment options primarily provide symptomatic relief but frequently come with considerable side effects, including depression, anxiety, and restlessness. Fibroblast growth factors (FGFs) are key signalling molecules regulating various cellular functions, including cell proliferation, differentiation, electrical excitability, and injury responses. Hence, several investigations claimed a relationship between FGFs and neurological disorders, and their findings indicated that they could be used as therapeutic targets for neurological disorders. The FGFs are reported to activate various signalling pathways, including Ras/MAPK/PI3k/Akt, and downregulate the GSK-3β/NF-κB pathways responsible for anti-oxidant, anti-inflammatory, and anti-apoptotic effects. Therefore, researchers are interested in developing novel treatment options for neurological disorders. The emergence of unreported FGFs contributes to our understanding of their involvement in these conditions and encourages further exploration of innovative therapeutic approaches. All the data were obtained from published articles using PubMed, Web of Science, and Scopus databases using the search terms Fibroblast Growth Factor, PD, HD, AD, ALS, signalling pathways, and neurological disorders.}, } @article {pmid40281113, year = {2025}, author = {Sasaki, D and Tenda, M and Sohma, Y}, title = {Semi-synthesis of TDP-43 reveals the effects of phosphorylation in N-terminal domain on self-association.}, journal = {Communications chemistry}, volume = {8}, number = {1}, pages = {125}, pmid = {40281113}, issn = {2399-3669}, support = {JP21H02602, JP24K02153, JP24H01787, JP24K09344//MEXT | Japan Society for the Promotion of Science (JSPS)/ ; }, abstract = {TDP-43, a nucleocytoplasmic shuttle protein consisting of 414 residues, forms self-association in the nucleus for physiological gene regulation, while aggregation into amyloid (consisting of aberrant β-sheets) in the cytoplasm causes neurodegenerative diseases such as amyotrophic lateral sclerosis. Post-translational phosphorylation of TDP-43 alters the self-association properties, which affects both the physiological function in the nucleus and the amyloidogenic potential in the cytoplasm, thereby impacting upon disease progression. However, insight into the role of per-residue phosphorylation in the self-association remains limited due to the difficulty in obtaining site-specifically phosphorylated TDP-43. Here, we demonstrate semi-synthesis of full-length TDP-43 that is uniformly phosphorylated at the 48th serine residue (designated as TDP1-414[pS48]). The synthetic scheme consisting of native chemical ligation followed by His-tag affinity chromatography efficiently gave TDP1-414(pS48) with a high purity. Interestingly, unlike non-phosphorylated TDP-43, the phosphorylated TDP-43 was found to have weak self-association property and to form aggregates that were not typical amyloid fibrils. Furthermore, chemical synthesis and three-dimensional structure analysis of the N-terminal domain (NTD, corresponding to TDP1-80) suggested that the phosphate ion at Ser48 weakens the inter-NTD interaction by inducing electrostatic repulsion. It significantly advances understanding of the pathological mechanisms involved in the post-translational modifications of TDP-43 associated with the neurodegenerative diseases.}, } @article {pmid40280464, year = {2025}, author = {Gritsiuta, AI and Reep, G and Parupudi, S and Petrov, RV}, title = {Optimizing the management of anastomotic leaks after esophagectomy: a narrative review of salvage strategies and outcomes.}, journal = {Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract}, volume = {29}, number = {7}, pages = {102069}, doi = {10.1016/j.gassur.2025.102069}, pmid = {40280464}, issn = {1873-4626}, mesh = {Humans ; *Esophagectomy/adverse effects ; *Anastomotic Leak/therapy/etiology ; *Salvage Therapy/methods ; Drainage/methods ; Treatment Outcome ; Nutritional Support ; Anti-Bacterial Agents/therapeutic use ; }, abstract = {BACKGROUND: Anastomotic leaks (ALs) after esophagectomy remain a major postoperative complication, leading to increased morbidity, prolonged hospital stays, and higher mortality. Despite advancements in surgical techniques and perioperative care, AL management lacks standardized protocols. This review aimed to evaluate current salvage strategies, including conservative, endoscopic, and surgical approaches, to optimize outcomes and reduce complications.

METHODS: A comprehensive literature search was conducted using PubMed, Scopus, Cochrane Library, and Google Scholar databases to identify studies published between 2000 and 2025 on AL management after esophagectomy. Peer-reviewed clinical trials, guidelines, and expert consensus reports were reviewed, focusing on minimally invasive and surgical interventions, patient outcomes, and emerging treatment strategies.

RESULTS: AL management strategies were classified into 3 primary approaches. Conservative management includes nutritional support, antibiotic therapy, and percutaneous drainage, particularly for contained leaks. Endoscopic interventions, such as self-expanding metal stents and endoscopic vacuum-assisted closure, have shown high success rates, with vacuum-assisted closure achieving superior closure outcomes. Hybrid techniques, including stent-over-sponge and vacuum-assisted closure-stent, are emerging as promising alternatives. Surgical interventions remain the gold standard for severe or refractory leaks with options, including primary repair, esophageal diversion, and delayed conduit reconstruction.

CONCLUSION: A multidisciplinary approach is crucial for optimizing AL management, incorporating enhanced recovery protocols, early risk assessment, and individualized treatment plans. Endoscopic techniques have reduced the need for surgical revisions, but surgical intervention remains necessary for severe cases. Future research should focus on refining treatment algorithms, integrating novel technologies, and establishing standardized guidelines to improve patient survival and quality of life.}, } @article {pmid40280333, year = {2025}, author = {Kearney, CA and Needle, CD and Brinks, AL and Shapiro, J and Lacouture, ME and Lo Sicco, KI}, title = {Response to Venkatesh et al's "Analysis of breast health outcomes in women on oral 5-alpha reductase inhibitors: A single-center retrospective cohort study".}, journal = {Journal of the American Academy of Dermatology}, volume = {93}, number = {2}, pages = {e73-e76}, doi = {10.1016/j.jaad.2025.03.091}, pmid = {40280333}, issn = {1097-6787}, } @article {pmid40280271, year = {2025}, author = {Kopalli, SR and Behl, T and Baldaniya, L and Ballal, S and Joshi, KK and Arya, R and Chaturvedi, B and Chauhan, AS and Verma, R and Patel, M and Jain, SK and Wal, A and Gulati, M and Koppula, S}, title = {Neuroadaptation in neurodegenerative diseases: compensatory mechanisms and therapeutic approaches.}, journal = {Progress in neuro-psychopharmacology & biological psychiatry}, volume = {139}, number = {}, pages = {111375}, doi = {10.1016/j.pnpbp.2025.111375}, pmid = {40280271}, issn = {1878-4216}, mesh = {Humans ; *Neurodegenerative Diseases/therapy/physiopathology/metabolism/pathology ; *Neuronal Plasticity/physiology ; Animals ; *Adaptation, Physiological/physiology ; *Brain/physiopathology/pathology/metabolism ; }, abstract = {Progressive neuronal loss is a hallmark of neurodegenerative diseases including Alzheimer's, Parkinson's, Huntington's, and Amyotrophic Lateral Sclerosis (ALS), which cause cognitive and motor impairment. Delaying the onset and course of symptoms is largely dependent on neuroadaptation, the brain's ability to restructure in response to damage. The molecular, cellular, and systemic processes that underlie neuroadaptation are examined in this study. These mechanisms include gliosis, neurogenesis, synaptic plasticity, and changes in neurotrophic factors. Axonal sprouting, dendritic remodelling, and compensatory alterations in neurotransmitter systems are important adaptations observed in NDDs; nevertheless, these processes may shift to maladaptive plasticity, which would aid in the advancement of the illness. Amyloid and tau pathology-induced synaptic alterations in Alzheimer's disease emphasize compensatory network reconfiguration. Dopamine depletion causes a major remodelling of the basal ganglia in Parkinson's disease, and non-dopaminergic systems compensate. Both ALS and Huntington's disease rely on motor circuit rearrangement and transcriptional dysregulation to slow down functional deterioration. Neuroadaptation is, however, constrained by oxidative stress, compromised autophagy, and neuroinflammation, particularly in elderly populations. The goal of emerging therapy strategies is to improve neuroadaptation by pharmacologically modifying neurotrophic factors, neuroinflammation, and synaptic plasticity. Neurostimulation, cognitive training, and physical rehabilitation are instances of non-pharmacological therapies that support neuroplasticity. Restoring compensating systems may be possible with the use of stem cell techniques and new gene treatments. The goal of future research is to combine biomarkers and individualized medicines to maximize neuroadaptive responses and decrease the course of illness. In order to reduce neurodegeneration and enhance patient outcomes, this review highlights the dual function of neuroadaptation in NDDs and its potential as a therapeutic target.}, } @article {pmid40280150, year = {2025}, author = {Singer-Clark, T and Hou, X and Card, NS and Wairagkar, M and Iacobacci, C and Peracha, H and Hochberg, LR and Stavisky, SD and Brandman, DM}, title = {Speech motor cortex enables BCI cursor control and click.}, journal = {Journal of neural engineering}, volume = {22}, number = {3}, pages = {}, pmid = {40280150}, issn = {1741-2552}, support = {DP2 DC021055/DC/NIDCD NIH HHS/United States ; }, mesh = {Humans ; Male ; Middle Aged ; Amyotrophic Lateral Sclerosis/physiopathology ; *Brain-Computer Interfaces ; Electrodes, Implanted ; Electroencephalography/methods ; *Motor Cortex/physiology ; *Speech/physiology ; }, abstract = {Objective.Decoding neural activity from ventral (speech) motor cortex is known to enable high-performance speech brain-computer interface (BCI) control. It was previously unknown whether this brain area could also enable computer control via neural cursor and click, as is typically associated with dorsal (arm and hand) motor cortex.Approach.We recruited a clinical trial participant with amyotrophic lateral sclerosis and implanted intracortical microelectrode arrays in ventral precentral gyrus (vPCG), which the participant used to operate a speech BCI in a prior study. We developed a cursor BCI driven by the participant's vPCG neural activity, and evaluated performance on a series of target selection tasks.Main results.The reported vPCG cursor BCI enabled rapidly-calibrating (40 s), accurate (2.90 bits per second) cursor control and click. The participant also used the BCI to control his own personal computer independently.Significance.These results suggest that placing electrodes in vPCG to optimize for speech decoding may also be a viable strategy for building a multi-modal BCI which enables both speech-based communication and computer control via cursor and click. (BrainGate2 ClinicalTrials.gov ID NCT00912041).}, } @article {pmid40279947, year = {2025}, author = {de Carvalho, M and Oliveira Santos, M and Swash, M}, title = {Subclinical involvement of small hand muscles in early amyotrophic lateral sclerosis: Selective susceptibility leads to 'split hand' phenomenon.}, journal = {Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology}, volume = {174}, number = {}, pages = {173-177}, doi = {10.1016/j.clinph.2025.04.007}, pmid = {40279947}, issn = {1872-8952}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology/diagnosis ; Male ; Female ; Middle Aged ; *Hand/physiopathology/innervation ; *Muscle, Skeletal/physiopathology ; Aged ; Electromyography/methods ; Adult ; Motor Neurons/physiology ; }, abstract = {OBJECTIVES: Split-hand phenomenon is common in patients with amyotrophic lateral sclerosis (ALS), but it is unknown if first dorsal interosseous (FDI) and abductor pollicis brevis (ABP) are affected earlier than abductor digiti minimi (ADM). We aimed to address this issue.

METHODS: One clinically normal hand from ALS patients was investigated, including needle EMG of the FDI, motor amplitude, distal latency, F-waves, neurophysiological index (NI) and split-hand index (SHI). Hands were categorised as G1 (normal FDI) and G2 (FDI with neurogenic changes). In patients who agreed EMG of the 3 muscles was done. A subset of G1 patients underwent a second evaluation 4-5 months later.

RESULTS: We studied 133 patients; EMG of the 3 muscles was done in 77 patients. There was no evidence for an earlier loss of motor units in FDI/ABP. In G2 patients, CMAP amplitude and NI were significantly lower (p < 0.001), but ADM changes were minor. Reassessment of G1 patients confirmed significant SHI, and amplitude and NI decrease in all muscles, but F-waves frequency remained stable in ADM.

CONCLUSIONS: Loss of motor units in the 3 hand muscles began in parallel, but ADM spinal motoneurons showed stronger resistance to degeneration.

SIGNIFICANCE: Dysfunction of intrinsic spinal circuits can influence split-hand phenomenon.}, } @article {pmid40279084, year = {2025}, author = {Singh, P and Borkar, M and Doshi, G}, title = {Network pharmacology approach to unravel the neuroprotective potential of natural products: a narrative review.}, journal = {Molecular diversity}, volume = {}, number = {}, pages = {}, pmid = {40279084}, issn = {1573-501X}, abstract = {Aging is a slow and irreversible biological process leading to decreased cell and tissue functions with higher risks of multiple age-related diseases, including neurodegenerative diseases. It is widely accepted that aging represents the leading risk factor for neurodegeneration. The pathogenesis of these diseases involves complex interactions of genetic mutations, environmental factors, oxidative stress, neuroinflammation, and mitochondrial dysfunction, which complicate treatment with traditional mono-targeted therapies. Network pharmacology can help identify potential gene or protein targets related to neurodegenerative diseases. Integrating advanced molecular profiling technologies and computer-aided drug design further enhances the potential of network pharmacology, enabling the identification of biomarkers and therapeutic targets, thus paving the way for precision medicine in neurodegenerative diseases. This review article delves into the application of network pharmacology in understanding and treating neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease, and spinal muscular atrophy. Overall, this article emphasizes the importance of addressing aging as a central factor in developing effective disease-modifying therapies, highlighting how network pharmacology can unravel the complex biological networks associated with aging and pave the way for personalized medical strategies.}, } @article {pmid40278411, year = {2025}, author = {Di Sarno, A and Romano, F and Arianna, R and Serpico, D and Lavorgna, M and Savastano, S and Colao, A and Di Somma, C}, title = {Lipid Metabolism and Statin Therapy in Neurodegenerative Diseases: An Endocrine View.}, journal = {Metabolites}, volume = {15}, number = {4}, pages = {}, pmid = {40278411}, issn = {2218-1989}, abstract = {Background/aim: A growing body of evidence suggests a link between dyslipidemias and neurodegenerative diseases, highlighting the crucial role of lipid metabolism in the health of the central nervous system. The aim of our work was to provide an update on this topic, with a focus on clinical practice from an endocrinological point of view. Endocrinologists, being experts in the management of dyslipidemias, can play a key role in the prevention and treatment of neurodegenerative conditions, through precocious and effective lipid profile optimization. Methods: The literature was scanned to identify clinical trials and correlation studies on the association between dyslipidemia, statin therapy, and the following neurodegenerative diseases: Alzheimer's disease (AD), Parkisons's disease (PD), Multiple sclerosis (MS), and Amyotrophic lateral sclerosis (ALS). Results: Impaired lipid homeostasis, such as that frequently observed in patients affected by obesity and diabetes, is related to neurodegenerative diseases, such as AD, PD, and other cognitive deficits related to aging. AD and related dementias are now a real priority health problem. In the United States, there are approximately 7 million subjects aged 65 and older living with AD and related dementias, and this number is projected to grow to 12 million in the coming decades. Lipid-lowering therapy with statins is an effective strategy in reducing serum low-density lipoprotein cholesterol to normal range concentrations and, therefore, cardiovascular disease risk; moreover, statins have been reported to have a positive effect on neurodegenerative diseases. Conclusions: Several pieces of research have found inconsistent information following our review. There was no association between statin use and ALS incidence. More positive evidence has emerged regarding statin use and AD/PD. However, further large-scale prospective randomized control trials are required to properly understand this issue.}, } @article {pmid40277369, year = {2025}, author = {Kyheng, M and Babykina, G and Duhamel, A}, title = {Joint Latent Class Models: A Tutorial on Practical Applications in Clinical Research.}, journal = {Statistics in medicine}, volume = {44}, number = {8-9}, pages = {e70047}, pmid = {40277369}, issn = {1097-0258}, mesh = {Humans ; *Latent Class Analysis ; Software ; Longitudinal Studies ; Disease Progression ; *Models, Statistical ; *Biomedical Research/methods ; Linear Models ; Data Interpretation, Statistical ; Survival Analysis ; Computer Simulation ; }, abstract = {Joint latent class model is a statistical approach allowing to simultaneously account for two outcomes related to disease progression: A longitudinal measure (for example a biomarker) and time-to-event, in the context of a heterogeneous population. Within this approach, the linear mixed model, describing the longitudinal measure, is connected to the survival model, describing the risk of event occurrence, via a model for latent classes, describing an unobserved population heterogeneity; thus, the behavior of the two outcomes is assumed to be specific to each latent class. The theoretical properties of the model are established and the model is implemented in software. However, its complexity makes it difficult to manipulate by clinicians. In this paper, we propose a detailed tutorial for clinicians and applied statisticians on how to specify the model in R software in order to respond to concrete clinical questions, how to explore, manipulate, interpret the provided results. The tutorial is based on a real clinical dataset; for each clinical question the mathematical model specification and the R script for implementation are provided, and the estimation results and goodness-of-fit measures are detailed and interpreted.}, } @article {pmid40277009, year = {2025}, author = {Rohrbaugh, MK and Houseman, G and Cunningham, A and Dobak, S and Ilieva, H and Kreher, M}, title = {The Impact of Cognitive Impairment on Advance Care Planning and Healthcare Utilization in People With ALS.}, journal = {The American journal of hospice & palliative care}, volume = {}, number = {}, pages = {10499091251337464}, doi = {10.1177/10499091251337464}, pmid = {40277009}, issn = {1938-2715}, abstract = {ObjectiveHalf of people with amyotrophic lateral sclerosis (PALS) develop cognitive impairment and/or behavioral changes, which may affect decision-making ability and participation in advance care planning (ACP) discussions. We aimed to determine the impact cognitive impairment, as measured by the Edinburgh Cognitive and Behavioural ALS Screen (ECAS), has on PALS' ACP discussions and healthcare utilization.MethodsPALS from a retrospective chart review were categorized into 2 groups: cognitively intact or cognitively impaired (ALS Specific Score < 77, ALS Nonspecific Score < 24, ECAS Total Score < 105, and/or ECAS Behavior or Psychosis Score 1+). Documented advance directives (AD); ACP discussions; and rates of percutaneous endoscopic gastrostomy (PEG) placement, tracheostomy placement, hospitalization within 2 weeks of death, death in hospital, and hospice utilization were recorded. Late disease stage was defined as ALS Functional Rating Scale-Revised (ALSFRS-R) score ≤ 38. Group comparisons were completed using chi-square tests, Fisher's exact test, and independent samples t-tests with P < .05 significance.ResultsThirty-three (47.1%) of 70 PALS met ECAS criteria for cognitive impairment. Rates of AD for PEG placement, AD for tracheostomy placement, hospitalization within 2 weeks of death, death in hospital, and hospice enrollment were not significantly different between groups (P = .41, .62, .32, .30, .06, respectively) despite ALSFRS-R score ≥/< 38 (all P > .05). Conclusions: ACP discussions and healthcare utilization were not affected by cognitive impairment despite disease stage. It is unknown if cognitive impairment affects healthcare decision-making processes for PALS/families. Further research examining the effect of various provider communication strategies on outcomes is needed.}, } @article {pmid40276954, year = {2025}, author = {Manini, A and Vasta, R and Brusati, A and Scheveger, F and Peverelli, S and Maranzano, A and Doretti, A and Gentile, F and Colombo, E and Brunetti, M and Moglia, C and Canosa, A and Manera, U and Grassano, M and Gentilini, D and Messina, S and Verde, F and Morelli, C and Landers, JE and Traynor, BJ and Chiò, A and Silani, V and Calvo, A and Ratti, A and Ticozzi, N}, title = {KIF5A p.Pro986Leu Risk Variant and Accelerated Progression of Amyotrophic Lateral Sclerosis.}, journal = {Annals of clinical and translational neurology}, volume = {12}, number = {7}, pages = {1499-1503}, pmid = {40276954}, issn = {2328-9503}, support = {2018-12367768//Italian Ministry of Health/ ; //Intramural Research Program of the National Institutes of Health/ ; /AG/NIA NIH HHS/United States ; //Aldo Ravelli Center for Neurotechnology/ ; RF-2021-12374238//Italian Ministry of Health/ ; ZIA AG000935/ImNIH/Intramural NIH HHS/United States ; //Dept. of Pathophysiology and Transplantation, Università degli Studi di Milano/ ; //Italian Ministry of Education/ ; //Università degli Studi di Milano/ ; //Experimental Brain Therapeutics/ ; PNC-E3-2022-23683266//Italian Ministry of Health/ ; }, abstract = {This study explored the impact of KIF5A rs113247976 (p.Pro986Leu), a risk allele for amyotrophic lateral sclerosis (ALS), on phenotypic variability in two Italian ALS cohorts (discovery, n = 865; replication, n = 1174). The minor allele (T) frequency was 0.015. No patients were homozygous (TT), allowing comparison between wild type and heterozygous carriers only. Heterozygous carriers showed faster disease progression (ALSFRS-R preslope). Findings were validated across both cohorts. Multiple linear regression identified p.Leu986 and age at onset as ALSFRS-R preslope predictors. In conclusion, heterozygous p.Leu986 in KIF5A is associated with faster ALS progression, supporting its consideration for genetic screening in clinical trials.}, } @article {pmid40276468, year = {2025}, author = {Zhang, G and Chen, Y and Tang, L and Bai, L and Zhang, H and Liu, H and Fan, D}, title = {Impact of sleep quality on disease progression in early-stage amyotrophic lateral sclerosis.}, journal = {Frontiers in neurology}, volume = {16}, number = {}, pages = {1545463}, pmid = {40276468}, issn = {1664-2295}, abstract = {Non-motor symptoms are clinical manifestations of amyotrophic lateral sclerosis (ALS). However, few studies have examined these symptoms in patients with early-stage ALS. We conducted a cross-sectional study to explore non-motor symptoms in 69 patients with ALS within 18 months of disease onset. The Pittsburgh Sleep Quality Index (PSQI), the Epworth Sleepiness Scale (ESS), and the Hospital Anxiety and Depression Scale (HADS) were used to evaluate sleep quality, daytime sleepiness, and anxiety and depression, respectively. Differences in the abovementioned non-motor symptoms between ALS patients and age-/sex-matched caregivers were examined, and correlations between these symptoms and the clinical features of ALS were analyzed. Compared to caregivers, ALS patients were more likely to report poor sleep [odds ratio (OR) and 95% confidence interval (95% CI) = 2.664, 1.276-5.560; p = 0.009] and excessive daytime sleepiness (EDS) [OR and 95% CI = 5.135, 1.640-16.072; p = 0.005]. The PSQI scores in ALS patients correlated significantly with the disease progression rate [ΔFS = (48-score on the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised, ALSFRS-R)/disease duration] [β(95% CI) = 2.867 (0.397, 5.336), p = 0.024] and plasma neurofilament light chain (NfL) levels [β (95% CI) = 0.041 (0.012, 0.070), p = 0.008). Our results revealed that the patients with early-stage ALS experienced poor sleep quality and daytime sleepiness and suggested that low sleep quality may be related to more rapid disease progression. Confounders were not obvious in the early stage of ALS, and our results suggested that these symptoms may be related to more severe and extensive pathological changes in the central nervous system.}, } @article {pmid40275673, year = {2025}, author = {Olmstead, AJ and Lee, J and Skrzat, S and Simmons, Z}, title = {Everyday Communication Experiences of Persons With Amyotrophic Lateral Sclerosis and Their Caregivers: Implications for Novel Speech Interventions.}, journal = {Muscle & nerve}, volume = {72}, number = {1}, pages = {158-165}, pmid = {40275673}, issn = {1097-4598}, support = {R01 DC021714/DC/NIDCD NIH HHS/United States ; /NH/NIH HHS/United States ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/complications/psychology ; Male ; Female ; *Caregivers/psychology ; Middle Aged ; Aged ; *Speech Intelligibility/physiology ; *Dysarthria/etiology/rehabilitation/psychology ; *Speech Therapy/methods ; *Communication ; Adult ; Surveys and Questionnaires ; }, abstract = {INTRODUCTION/AIMS: Speech intelligibility decline is a common in dysarthria secondary to amyotrophic lateral sclerosis (ALS). However, interventions that focus on improving speech may not be able to counteract decline as the disease progresses. Researchers have suggested interventions that help PALS's communication partners tune their speech perception systems to PALS's production. In the current study, we take a first step to establishing the need and enthusiasm for such interventions on the part of PALS and their caregivers (CPALS).

METHODS: PALS and CPALS recruited from the Greater Philadelphia chapter of the ALS association completed novel questionnaires probing their everyday speech communication and speech intervention experiences. Questions focused especially on changes in communication partners' ability to understand PALS' speech. Both quantitative and qualitative data were recorded.

RESULTS: PALS (n = 21) and CPALS (n = 22) reported speech as a primary mode of communication despite declines in intelligibility. However, most also indicated variability in PALS's speech intelligibility depending on the communication partner, indicating that frequent communication partners were better able to understand PALS's speech. Both groups reported interest in interventions supporting speech intelligibility and were most interested in speech interventions that included PALS and CPALS together.

DISCUSSION: PALS and especially CPALS in our study expressed interest in speech interventions that involved both parties. Thus, there is both a need for and a desire in the community for interactive speech interventions that support intelligibility. Additionally, our findings lend support to clinical approaches targeting frequent communication partners in addition to PALS.}, } @article {pmid40275359, year = {2025}, author = {Grima, N and Smith, AN and Shepherd, CE and Henden, L and Zaw, T and Carroll, L and Rowe, DB and Kiernan, MC and Blair, IP and Williams, KL}, title = {Multi-region brain transcriptomic analysis of amyotrophic lateral sclerosis reveals widespread RNA alterations and substantial cerebellum involvement.}, journal = {Molecular neurodegeneration}, volume = {20}, number = {1}, pages = {40}, pmid = {40275359}, issn = {1750-1326}, support = {Discovery Grant//FightMND/ ; Grant-in-Aid//Motor Neurone Disease Research Australia/ ; R28AA012725/AA/NIAAA NIH HHS/United States ; Investigator Grant 1176913//National Health and Medical Research Council/ ; R28 AA012725/AA/NIAAA NIH HHS/United States ; Not applicable//Neuroscience Research Australia/ ; Angie Cunningham PhD Scholarship and Project Grant-In-Aid Award//FightMND/ ; Ideas Grant 2011120//National Health and Medical Research Council/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology ; *Cerebellum/metabolism/pathology ; Male ; Female ; Middle Aged ; Aged ; *Transcriptome/genetics ; *Brain/metabolism/pathology ; Gene Expression Profiling/methods ; Motor Cortex/metabolism/pathology ; Aged, 80 and over ; *RNA/genetics/metabolism ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that primarily affects the motor neurons, causing progressive muscle weakness and paralysis. While research has focused on understanding pathological mechanisms in the motor cortex and spinal cord, there is growing evidence that extra-motor brain regions may also play a role in the pathogenesis or progression of ALS.

METHODS: We generated 165 sample-matched post-mortem brain transcriptomes from 22 sporadic ALS patients with pTDP-43 pathological staging and 11 non-neurological controls. For each individual, five brain regions underwent mRNA sequencing: motor cortex (pTDP-43 inclusions always present), prefrontal cortex and hippocampus (pTDP-43 inclusions sometimes present), and occipital cortex and cerebellum (pTDP-43 inclusions rarely present). We examined gene expression, cell-type composition, transcript usage (% contribution of a transcript to total gene expression) and alternative splicing, comparing ALS-specific changes between brain regions. We also considered whether post-mortem pTDP-43 pathological stage classification defined ALS subgroups with distinct gene expression profiles.

RESULTS: Significant gene expression changes were observed in ALS cases for all five brain regions, with the cerebellum demonstrating the largest number of total (> 3,000) and unique (60%) differentially expressed genes. Pathway enrichment and predicted activity were largely concordant across brain regions, suggesting that ALS-linked mechanisms, including inflammation, mitochondrial dysfunction and oxidative stress, are also dysregulated in non-motor brain regions. Switches in transcript usage were identified for a small set of genes including increased usage of a POLDIP3 transcript, associated with TDP-43 loss-of-function, in the cerebellum and a XBP1 transcript, indicative of unfolded protein response activity, in the motor cortex. Extensive variation in RNA splicing was identified in the ALS brain, with 26-41% of alternatively spliced genes unique to a given brain region. This included detection of TDP-43-associated cryptic splicing events such as the STMN2 cryptic exon which was shown to have a pTDP-43 pathology-specific expression pattern. Finally, ALS patients with stage 4 pTDP-43 pathology demonstrated distinct gene and protein expression changes in the cerebellum.

CONCLUSIONS: Together our findings highlighted widespread transcriptome alterations in ALS post-mortem brain and showed that, despite the absence of pTDP-43 pathology in the cerebellum, extensive and pTDP-43 pathological stage-specific RNA changes are evident in this brain region.}, } @article {pmid40273110, year = {2025}, author = {Souza, AA and Silva, STD and Régis, AMP and Aires, DN and Pondofe, KM and Melo, LP and Valentim, RAM and Lindquist, ARR and Macedo, LRD and Ribeiro, TS}, title = {Muscle strengthening in individuals with Amyotrophic Lateral Sclerosis: a systematic review with meta-analyses.}, journal = {PloS one}, volume = {20}, number = {4}, pages = {e0320788}, pmid = {40273110}, issn = {1932-6203}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology/rehabilitation/therapy ; *Muscle Strength/physiology ; *Resistance Training/methods ; *Exercise Therapy/methods ; }, abstract = {Despite the observed benefits of properly prescribed exercises for people with Amyotrophic Lateral Sclerosis (ALS), the scarcity of studies and lack of consensus on the effects of muscle-strengthening exercises on this population has a negative impact on their rehabilitation. This study aimed to evaluate the effects of muscle-strengthening interventions in individuals with ALS. This systematic review of intervention studies included clinical trials that performed non-respiratory muscle strengthening in people with ALS compared to non-strengthening interventions, usual care, or placebo. Such studies were obtained from the MEDLINE, EMBASE, Cochrane Library, SPORTDiscus, and Physiotherapy Evidence Database databases, with no language or publication date restrictions. The outcomes considered were peripheral muscle strength, functionality, fatigue, and adverse events. The Physiotherapy Evidence Database scale was used to analyze the risk of bias, while the Grading of Recommendations Assessment, Development and Evaluation system was used to evaluate the quality of the evidence. Searches were conducted in October 2023 and eight studies were included, totaling 296 individuals. Seven of the eight studies showed superiority of the experimental intervention over the control, but this was not supported in the meta-analyses. Small sample size and high heterogeneity in the primary studies contributed significantly to the low quality of the evidence. There was no evidence of the superiority of interventions for muscle strengthening compared to interventions not aimed at strengthening, usual care, or placebo in terms of the outcomes analyzed immediately after the intervention. The quality of the evidence ranged from low to very low. Five of the studies evaluated adverse events, without reporting serious events. Interventions for muscle strengthening did not prove to be more effective when compared to the control group in the short term nor seem to produce serious adverse events. The low quality of the evidence indicates the need for studies with greater methodological rigor in this population, to more assertively assess the impacts of this intervention over the short, medium, and long term.}, } @article {pmid40272376, year = {2025}, author = {Nguyen, THV and Ferron, F and Murakami, K}, title = {Neurotoxic Implications of Human Coronaviruses in Neurodegenerative Diseases: A Perspective from Amyloid Aggregation.}, journal = {ACS chemical biology}, volume = {20}, number = {5}, pages = {983-992}, doi = {10.1021/acschembio.5c00153}, pmid = {40272376}, issn = {1554-8937}, mesh = {Humans ; *Neurodegenerative Diseases/virology/metabolism ; *Amyloid/metabolism/chemistry ; *Coronavirus/metabolism/pathogenicity ; *Coronavirus Infections/complications/virology ; }, abstract = {Human coronaviruses (HCoVs) include seven species: HCoV-229E, HCoV-NL63, HCoV-OC43, HCoV-HKU1, MERS-CoV, SARS-CoV-1, and SARS-CoV-2. The last three, classified as Betacoronaviruses, are highly transmissible and have caused severe pandemics. HCoV infections primarily affect the respiratory system, leading to symptoms such as dry cough, fever, and breath shortness, which can progress to acute respiratory failure and death. Beyond respiratory effects, increasing evidence links HCoVs to neurological dysfunction. However, distinguishing direct neural complications from preexisting disorders, particularly in the elderly, remains challenging. This study examines the association between HCoVs and neurodegenerative diseases like Alzheimer disease, Parkinson disease, Lewy body dementia, amyotrophic lateral sclerosis, and Creutzfeldt-Jakob disease. It also presents the long-term neurological effects of HCoV infections and their differential impact across age groups and sexes. A key aspect of this study is the investigation of the sequence and structural similarities between amyloidogenic and HCoV spike proteins, which can provide insights into potential neuropathomechanisms.}, } @article {pmid40271431, year = {2025}, author = {Rana, A and Katiyar, A and Arun, A and Berrios, JN and Kumar, G}, title = {Natural sulfur compounds in mental health and neurological disorders: insights from observational and intervention studies.}, journal = {Frontiers in nutrition}, volume = {12}, number = {}, pages = {1534000}, pmid = {40271431}, issn = {2296-861X}, abstract = {Over the years, the global disease burden of neurological disorders (NDs) and mental disorders (MDs) has significantly increased, making them one of the most critical concerns and challenges to human health. In pursuit of novel therapies against MD and ND, there has been a growing focus on nutrition and health. Dietary sulfur, primarily derived from various natural sources, plays a crucial role in numerous physiological processes, including brain function. This review offers an overview of the chemical composition of several natural sources of the sulfur-rich substances such as isothiocyanates, sulforaphane, glutathione, taurine, sulfated polysaccharides, allyl sulfides, and sulfur-containing amino acids, all of which have neuroprotective properties. A multitude of studies have documented that consuming foods that are high in sulfur enhances brain function by improving cognitive parameters and reduces the severity of neuropathology by exhibiting antioxidant and anti-inflammatory properties at the molecular level. In addition, the growing role of natural sulfur compounds in repairing endothelial dysfunction, compromising blood-brain barrier and improving cerebral blood flow, are documented here. Furthermore, this review covers the encouraging results of supplementing sulfur-rich diets in many animal models and clinical investigations, along with their molecular targets in MD, such as schizophrenia, depression, anxiety, bipolar disorder, and autism spectrum disorder, and ND, such as Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic Lateral Sclerosis (ALS), and Multiple Sclerosis (MS). The prospects of natural sulfur compounds show great promise as they have potential applications in nutraceuticals, medicines, and functional foods to enhance brain function and prevent diseases. However, additional research is required to clarify the mechanisms by which it works, enhance its bioavailability, and evaluate its long-term safety for broad use.}, } @article {pmid40271315, year = {2025}, author = {Honda, N and Watanabe, Y and Honda, H and Uemoto, M and Fukuhara, H and Hanajima, R}, title = {Implications of Mutant SOD1 on RNA Processing and Interferon Responses in Amyotrophic Lateral Sclerosis: Omics Data Analysis.}, journal = {Cureus}, volume = {17}, number = {3}, pages = {e81045}, pmid = {40271315}, issn = {2168-8184}, abstract = {INTRODUCTION: Cytoplasmic inclusions are observed in motor neurons in amyotrophic lateral sclerosis (ALS) associated with the Cu/Zn superoxide dismutase mutation (mtSOD1). Although these inclusions are a hallmark of the disorder, degeneration is not necessarily initiated in the cytoplasm, nor are these structures the culprit of ALS. The nucleus stores genetic material and acts as the cell's control center, and a small fraction of mtSOD1 is reported to be distributed in the nucleus. We hypothesized that mtSOD1 in the nucleus contributes to motor neuron degeneration.

METHODS: We explored the roles of mtSOD1 in relation to nuclear proteins, chromosomal DNA, and mRNA expression. An immortalized cell line derived from a transgenic ALS mouse model expressing mtSOD1-L126delTT with a FLAG was used for stable immunoprecipitation of mtSOD1-binding molecules using shotgun proteomics and chromatin immunoprecipitation-sequencing (ChIP-seq). We also examined mRNA expression by silencing whole SOD1 (innate mouse Sod1 and mtSOD1) or mtSOD1 alone and compared these patterns against those in non-silenced counterparts.

RESULTS: We identified 392 mtSOD1-interacting proteins in the nucleus. Gene ontology (GO) revealed these proteins to be enriched for "mRNA processing." Notably, more than 11% of mtSOD1-interacting proteins were expressed concurrently with previously reported wild-type TAR DNA-binding protein 43 (TDP-43)-interacting proteins. ChIP-seq revealed that mtSOD1-interacting DNA portions showed a preference for zinc finger protein-binding motifs. GO analysis of the ChIP-seq data revealed that "mRNA processing" was again enriched among the genes harboring mtSOD1-binding domains. RNA expression analyses revealed that the presence of mouse Sod1 and mtSOD1 induced the overexpression of molecules related to "type 1 IFN responses."

CONCLUSIONS: We revealed that mtSOD1 interacted with nuclear proteins and specific DNA segments and that RNA expression was notably altered when mouse Sod1 and mtSOD1 were silenced. These interactions could play a pivotal role in motor neuron degeneration.}, } @article {pmid40268233, year = {2025}, author = {Basak, B and Holzbaur, ELF}, title = {Mitophagy in Neurons: Mechanisms Regulating Mitochondrial Turnover and Neuronal Homeostasis.}, journal = {Journal of molecular biology}, volume = {437}, number = {18}, pages = {169161}, doi = {10.1016/j.jmb.2025.169161}, pmid = {40268233}, issn = {1089-8638}, mesh = {*Mitophagy ; Humans ; *Neurons/metabolism ; *Homeostasis ; *Mitochondria/metabolism ; Animals ; Ubiquitin-Protein Ligases/metabolism/genetics ; Protein Kinases/metabolism ; *Mitochondrial Turnover ; Parkinson Disease/metabolism ; }, abstract = {Mitochondrial quality control is instrumental in regulating neuronal health and survival. The receptor-mediated clearance of damaged mitochondria by autophagy, known as mitophagy, plays a key role in controlling mitochondrial homeostasis. Mutations in genes that regulate mitophagy are causative for familial forms of neurological disorders including Parkinson's disease (PD) and Amyotrophic lateral sclerosis (ALS). PINK1/Parkin-dependent mitophagy is the best studied mitophagy pathway, while more recent work has brought to light additional mitochondrial quality control mechanisms that operate either in parallel to or independent of PINK1/Parkin mitophagy. Here, we discuss our current understanding of mitophagy mechanisms operating in neurons to govern mitochondrial homeostasis. We also summarize progress in our understanding of the links between mitophagic dysfunction and neurodegeneration, and highlight the potential for therapeutic interventions to maintain mitochondrial health and neuronal function.}, } @article {pmid40267658, year = {2025}, author = {Orsucci, D and Vista, M and Santorelli, FM}, title = {Conversational AI in neurogenetics. The example of FUS gene.}, journal = {Journal of the neurological sciences}, volume = {473}, number = {}, pages = {123511}, doi = {10.1016/j.jns.2025.123511}, pmid = {40267658}, issn = {1878-5883}, } @article {pmid40267619, year = {2025}, author = {Garnés-Camarena, O and Mahíllo-Fernández, I and Martínez-Ulloa, P and Mandeville, R and Lorenzo, O and Stashuk, DW}, title = {Towards early diagnosis of amyotrophic lateral sclerosis using near fibre EMG.}, journal = {Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology}, volume = {174}, number = {}, pages = {114-122}, doi = {10.1016/j.clinph.2025.04.006}, pmid = {40267619}, issn = {1872-8952}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/physiopathology ; *Electromyography/methods ; Male ; Female ; Middle Aged ; Aged ; Retrospective Studies ; Early Diagnosis ; Adult ; Motor Neurons/physiology ; Muscle, Skeletal/physiopathology/innervation ; *Muscle Fibers, Skeletal/physiology ; Action Potentials/physiology ; }, abstract = {OBJECTIVE: Amyotrophic lateral sclerosis (ALS) is characterized by progressive loss of motor neurons and diagnosis is usually delayed several months. The continuous denervation and reinnervation associated with ALS are manifest in EMG signals as changes in motor unit potential (MUP) size, temporal dispersion and instability. Near Fibre EMG is a novel method to assess early changes in MUP temporal dispersion and instability using routinely recorded EMG signals in a semi-automated manner.

METHODS: Near Fibre EMG values from 2318 MUs, retrospectively sampled at the time of ALS diagnosis, from 96 muscles of 15 patients were compared with values from 3954 MUs sampled from 109 muscles of 84 reference subjects.

RESULTS: 30.1% and 46.1% of ALS MUs had MUPs with increased complexity or instability, respectively, and 17.4% had both. The potential importance and heightened sensitivity of NFEMG was highlighted when analyzing normal-sized motor units; as many as 24% of the normal-sized MUPs actually had significant instability, while 14% had increased complexity, and 7.4% had both.

CONCLUSIONS: Near Fibre EMG can characterize motor unit electrophysiological status and hence help quantify the degree, and course of denervation and reinnervation.

SIGNIFICANCE: Near-Fiber EMG offers the potential to facilitate earlier ALS diagnosis, which, as promising therapies become available, can be consequential.}, } @article {pmid40267236, year = {2025}, author = {Zhong, H and Zhu, J and Liu, S and Zhou, D and Long, Q and Wu, C and Zhao, B and Cheng, C and Yang, Y and Wu, Q and Wu, Y and Li, C and Wang, Z and Wu, J and Guo, X and Zhi, D and Deng, Y and Wu, L}, title = {Linking DNA methylation in brain regions to Alzheimer's disease risk: a Mendelian randomization study.}, journal = {Human molecular genetics}, volume = {34}, number = {12}, pages = {1026-1033}, doi = {10.1093/hmg/ddaf053}, pmid = {40267236}, issn = {1460-2083}, support = {//University of Hawai'i Cancer Center/ ; }, mesh = {Humans ; *DNA Methylation/genetics ; *Alzheimer Disease/genetics/pathology/metabolism ; Mendelian Randomization Analysis ; Quantitative Trait Loci/genetics ; Polymorphism, Single Nucleotide/genetics ; *Brain/metabolism/pathology ; Genetic Predisposition to Disease ; Male ; Female ; CpG Islands/genetics ; Aged ; Genome-Wide Association Study ; Risk Factors ; }, abstract = {AIM: DNA methylation in brain regions represents a potential mechanism linking genetic variation to Alzheimer's disease (ad) risk, yet most studies have focused on blood-derived methylation markers. In this study, we conducted a systematic Mendelian randomization (MR) study to evaluate associations between predicted brain region-specific DNA methylation levels and ad risk, using methylation quantitative trait loci (mQTL) as genetic instruments.

METHODS: We analyzed mQTLs from five human brain regions: cerebellum (CRBLM), frontal cortex (FCTX), causal pons (PONS), and temporal cortex (TCTX) from 600 individuals in Gibbs et al's study, as well as mQTLs from dorsolateral prefrontal cortex (DLPFC) of 543 participants in the Religious Orders Study and the Rush Memory and Aging Project (ROSMAP). In our MR analyses, we integrated these mQTLs with single nucleotide polymorphisms (SNP)-ad risk summary statistics derived from 85 934 ad-related cases and 401 577 normal controls.

RESULTS: Among 62 554 cytosine-guanine dinucleotide (CpG) sites, we identified 597 CpG sites (CpGs) significantly associated with ad risk (false discovery rate (FDR) < 0.05). Of these, 289 were confirmed through colocalization and summary-based MR (SMR) analyses, including one CpG site in CRBLM, 285 in DLPFC, one in FCTX, two in PONS, and one in TCTX. By integrating gene expression data, we identified 19 CpG sites with consistent associations across methylation levels, expression of eight target genes, and ad risk, including novel regulatory mechanisms involving RITA1's modulation of cg11558705 and PCGF3's regulation of cg10009224.

CONCLUSION: Our findings highlight brain region-specific DNA methylation as a mediator of genetic risk for ad, offering insights into ad pathogenesis and identifying potential therapeutic targets.}, } @article {pmid40267187, year = {2025}, author = {Guillaud, L and Garanzini, A and Zakhia, S and De la Fuente, S and Dimitrov, D and Boerner, S and Terenzio, M}, title = {Loss of intracellular ATP affects axoplasmic viscosity and pathological protein aggregation in mammalian neurons.}, journal = {Science advances}, volume = {11}, number = {17}, pages = {eadq6077}, pmid = {40267187}, issn = {2375-2548}, mesh = {*Adenosine Triphosphate/metabolism ; Humans ; Animals ; *Protein Aggregation, Pathological/metabolism/pathology ; Mice ; *Neurons/metabolism ; Induced Pluripotent Stem Cells/metabolism ; Amyotrophic Lateral Sclerosis/metabolism/pathology ; *Axons/metabolism ; Viscosity ; Mitochondria/metabolism ; Protein Aggregates ; Parkinson Disease/metabolism/pathology ; DNA-Binding Proteins/metabolism ; Alzheimer Disease/metabolism/pathology ; }, abstract = {Neurodegenerative diseases display synaptic deficits, mitochondrial defects, and protein aggregation. We show that intracellular adenosine triphosphate (ATP) regulates axoplasmic viscosity and protein aggregation in mammalian neurons. Decreased intracellular ATP upon mitochondrial inhibition leads to axoterminal cytosol, synaptic vesicles, and active zone component condensation, modulating the functional organization of mouse glutamatergic synapses. Proteins involved in the pathogenesis of Parkinson's disease (PD), Alzheimer's disease (AD), and amyotrophic lateral sclerosis (ALS) condensed and underwent ATP-dependent liquid phase separation in vitro. Human inducible pluripotent stem cell-derived neurons from patients with PD and ALS displayed reduced axoplasmic fluidity and decreased intracellular ATP. Last, nicotinamide mononucleotide treatment successfully rescued intracellular ATP levels and axoplasmic viscosity in neurons from patients with PD and ALS and reduced TAR DNA-binding protein 43 (TDP-43) aggregation in human motor neurons derived from a patient with ALS. Thus, our data suggest that the hydrotropic activity of ATP contributes to the regulation of neuronal homeostasis under both physiological and pathological conditions.}, } @article {pmid40265300, year = {2025}, author = {Xu, IQ and Guo, L and Xu, J and Setiawan, S and Deng, X and Lo, YL and Chai, JYH and Simmons, Z and Ramasamy, S and Yeo, CJJ}, title = {Predictive Analysis of Amyotrophic Lateral Sclerosis Progression and Mortality in a Clinic Cohort From Singapore.}, journal = {Muscle & nerve}, volume = {72}, number = {1}, pages = {71-81}, pmid = {40265300}, issn = {1097-4598}, support = {C210112024//Agency for Science, Technology and Research/ ; IRNMR21CPGJJ//National Neuroscience Institute/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/mortality/diagnosis/epidemiology ; Singapore/epidemiology ; Male ; Female ; Middle Aged ; Aged ; *Disease Progression ; Registries ; Retrospective Studies ; Cohort Studies ; Machine Learning ; Adult ; }, abstract = {INTRODUCTION: There is currently no comprehensive Amyotrophic Lateral Sclerosis (ALS) patient database in Singapore comparable to those available in Europe and the United States. We established the Singapore ALS registry (SingALS) to draw meaningful inferences about the ALS population in Singapore through developing statistical and machine learning-based predictive models.

METHODS: The SingALS registry was established through the retrospective collection of demographic, clinical, and laboratory data from 72 ALS patients at Tan Tock Seng Hospital (TTSH) and combining it with demographic and clinical data from 71 patients at Singapore General Hospital (SGH). The SingALS was compared against international ALS registries. Using comparative studies including survival and temporal feature analysis, we identified key factors influencing ALS survival and developed a machine learning model to predict survival outcomes.

RESULTS: Compared to Caucasian-dominant registries, such as the German Swabia registry, SingALS patients had longer average survival (50.51 vs. 31.0 months), younger age of onset (56.18 vs. 66.6 years), and lower bulbar onset prevalence (20.98% vs. 34.10%). Singaporean males had poorer outcomes compared to females, with a hazard ratio (HR) of 3.12 (p = 0.008). Patients who died within 24 months had an earlier need for being bedbound (p < 0.004), percutaneous endoscopic gastrostomy (PEG) insertion (p = 0.004) and non-invasive ventilation (NIV) (p < 0.001). Machine learning and statistical analysis indicated that a steeper ALSFRS-R slope, higher alkaline phosphatase (ALP), white blood cell (WBC), absolute neutrophil counts, and creatinine levels are associated with worse mortality.

DISCUSSION: We developed a comprehensive Singaporean ALS registry and identified key factors influencing survival.}, } @article {pmid40265276, year = {2025}, author = {Mendonça, IP and Peixoto, CA}, title = {The Double-Edged Sword: The Complex Function of Enteric Glial Cells in Neurodegenerative Diseases.}, journal = {Journal of neurochemistry}, volume = {169}, number = {4}, pages = {e70069}, doi = {10.1111/jnc.70069}, pmid = {40265276}, issn = {1471-4159}, support = {CNPq;#301891/2022-2//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; IAM-PROEP# 005-FIO-22//Instituto Aggeu Magalhães/ ; }, mesh = {Humans ; *Neurodegenerative Diseases/pathology/metabolism ; *Neuroglia/metabolism/pathology/physiology ; Animals ; *Enteric Nervous System/pathology/metabolism ; }, abstract = {Over the past two decades, a growing number of studies have been conducted on the role of bidirectional communication through the gut-brain axis in the development of neurodegenerative diseases. These studies were driven by the curious fact that all of these diseases present varying degrees of intestinal involvement included in their wide range of symptoms. A population of cells belonging to the ENS, called enteric glial cells (EGCs), appears to actively participate in this communication between the intestine and the brain, but acting in a dualistic manner, sometimes in reactive gliosis releasing inflammatory mediators, sometimes promoting homeostasis and resilience in the face of inflammatory injuries. To date, the intracellular mechanisms that define the transcriptional profile expressed in EGCs in each situation have not yet been elucidated. This review proposes a discussion on: (1) the complex role of distinct phenotypes of enteric glial cells involved in neurodegenerative diseases, such as Parkinson's disease (PD), Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD) and multiple sclerosis (MS); and (2) innovative strategies such as IDO/TDO inhibitors, Brazil nuts, caffeic acid, polyphenols, among others, that act on EGCs and have the potential to treat neurodegenerative diseases.}, } @article {pmid40264898, year = {2024}, author = {Kumar, J and Varela-Ramirez, A and Narayan, M}, title = {Development of novel carbon-based biomedical platforms for intervention in xenotoxicant-induced Parkinson's disease onset.}, journal = {BMEmat}, volume = {2}, number = {4}, pages = {}, pmid = {40264898}, issn = {2751-7446}, support = {G12 MD007592/MD/NIMHD NIH HHS/United States ; R16 GM145575/GM/NIGMS NIH HHS/United States ; }, abstract = {Chronic exposure to herbicides, weedicides, and pesticides is associated with the onset and progress of neurodegenerative disorders such as Parkinson's disease (PD), Alzheimer's disease (AD), and Amyotrophic Lateral Sclerosis (ALS). Here, we have investigated whether quinic- and chlorogenic-acid-derived Carbon Quantum Dots (QACQDs and ChACQDs, respectively) protect against a (pesticide) paraquat-insult model of PD. Our results indicated that both types of CQDs intervened in the soluble-to-toxic transformation of the amyloid-forming model protein Hen Egg White Lysozyme (HEWL). Furthermore, QACQDs and ChACQDs demonstrated antioxidant activity while remaining biocompatible in a human neuroblastoma-derived cell line (SH-SY5Y) up to 5 mg/ml and protected the cell line from the environmental neurotoxicant (paraquat). Importantly, both CQDs were found to protect dopaminergic neuronal ablation in a paraquat model of Parkinson's disease using the nematode C. elegans. Our results are significant because both plant-derived organic acids cross the blood-brain barrier, making them attractive for developing CQD architectures. Furthermore, since the synthesis of these CQDs was performed using green chemistry methods from precursor acids that cross the BBB, these engineered bionanomaterial platforms are tantalizing candidates for preventing neurodegenerative disorders associated with exposure to environmental neurotoxicants.}, } @article {pmid40263468, year = {2025}, author = {Su, Y and Schwartz, M and Fayad, I and García, M and Zavala, MA and Tijerín-Triviño, J and Astigarraga, J and Cruz-Alonso, V and Liu, S and Zhang, X and Chen, S and Ritter, F and Besic, N and d'Aspremont, A and Ciais, P}, title = {Canopy height and biomass distribution across the forests of Iberian Peninsula.}, journal = {Scientific data}, volume = {12}, number = {1}, pages = {678}, pmid = {40263468}, issn = {2052-4463}, support = {ANR-22-FAI1-0002//Agence Nationale de la Recherche (French National Research Agency)/ ; ANR-22-FAI1-0002//Agence Nationale de la Recherche (French National Research Agency)/ ; ANR-22-FAI1-0002//Agence Nationale de la Recherche (French National Research Agency)/ ; ANR-22-FAI1-0002//Agence Nationale de la Recherche (French National Research Agency)/ ; }, mesh = {*Forests ; *Biomass ; Spain ; Remote Sensing Technology ; *Trees ; Ecosystem ; Climate Change ; Deep Learning ; }, abstract = {Accurate mapping of vegetation canopy height and biomass distribution is essential for effective forest monitoring, climate change mitigation, and sustainable forestry. Here we present high-resolution remote sensing-based canopy height (10 m resolution) and above ground biomass (AGB, 50 m resolution) maps for the forests of the Iberian Peninsula from 2017 to 2021, using a deep learning framework that integrates Sentinel-1, Sentinel-2, and LiDAR data. Two UNET models were developed: one trained on Airborne Laser Scanning (ALS) data (MAE: 1.22 m), while another using Global Ecosystem Dynamics Investigation (GEDI) footprints (MAE: 3.24 m). External validation with 6,308 Spanish National Forest Inventory (NFI) plots (2017-2019) confirmed canopy height reliability, showing MAEs of 2-3 m in tree-covered areas. AGB estimates were obtained through Random Forest models that linked UNET derived height predictions to NFI AGB data, achieves an MAE of ~29 Mg/ha. The creation of high-resolution maps of canopy height and biomass across various forest landscapes in the Iberian Peninsula provides a valuable new tool for environmental researchers, policy makers, and forest management professionals, offering detailed insights that can inform conservation strategies, carbon sequestration efforts, and sustainable forest management practices.}, } @article {pmid40262868, year = {2025}, author = {Shi, Y and Wu, Z and Cheng, R and Zhang, L and Guo, X and Li, X and Bi, Y}, title = {The Trp-574-Leu mutations together with enhanced metabolism contribute to cross-resistance to ALS inhibiting herbicides in Fimbristylis littoralis.}, journal = {Pesticide biochemistry and physiology}, volume = {210}, number = {}, pages = {106385}, doi = {10.1016/j.pestbp.2025.106385}, pmid = {40262868}, issn = {1095-9939}, mesh = {*Acetolactate Synthase/genetics/antagonists & inhibitors/metabolism ; *Herbicides/pharmacology ; *Herbicide Resistance/genetics ; Mutation ; Molecular Docking Simulation ; *Plant Proteins/genetics/metabolism/antagonists & inhibitors ; Sulfonylurea Compounds/pharmacology ; Piperonyl Butoxide/pharmacology ; }, abstract = {Fimbristylis littoralis Gaudich., an important weed in Chinese paddy fields, has caused significant yield losses in rice and other crops. Acetolactate synthase (ALS) inhibitors, such as halosulfuron-methyl, are widely used for weed control. This study identified a highly resistant population (R23-1) of F. littoralis to halosulfuron-methyl, with an exceptionally high resistance index (RI) of 3441.66. The resistant mechanisms of F. littoralis to ALS inhibitors have not been reported previously. We employed a comprehensive approach to address this, including whole-plant bioassay, ALS target gene sequencing, molecular docking, synergistic tests with metabolic enzyme inhibitors, glutathione S-transferases (GSTs) activity assays, and cross-resistance testing. The results revealed the first report of a Trp-574-Leu mutation in the ALS gene of the R23-1 population, which significantly increased binding energy, as shown by molecular docking analysis. Synergistic tests demonstrated that the cytochrome P450 monooxygenase (P450) inhibitor piperonyl butoxide (PBO) and the GSTs inhibitor 4-chloro-7-nitro-1,2,3-benzoxadiazole (NBD-Cl) markedly enhanced the sensitivity of the R23-1 population to halosulfuron-methyl, with synergistic ratios of 4.11 and 8.15, respectively, while malathion had no effect. GST activity decreased in both populations after halosulfuron-methyl treatment, with the R23-1 population consistently showing significantly higher levels, peaking on day five. Furthermore, the R23-1 population demonstrated cross-resistance to multiple ALS inhibitors. These findings provide novel insights into the resistance mechanisms of F. littoralis and lay a theoretical foundation for developing effective strategies to mitigate or delay the evolution of resistance.}, } @article {pmid40262704, year = {2025}, author = {Kim, HB and Ehsan, MF and Alshawabkeh, AN and Kim, JG}, title = {Electrochemical activation of alum sludge for the adsorption of lead (Pb(II)) and arsenic (As): Mechanistic insights and machine learning (ML) analysis.}, journal = {Bioresource technology}, volume = {430}, number = {}, pages = {132563}, doi = {10.1016/j.biortech.2025.132563}, pmid = {40262704}, issn = {1873-2976}, mesh = {Adsorption ; *Lead/isolation & purification/chemistry ; *Machine Learning ; *Sewage/chemistry ; *Alum Compounds/chemistry ; *Arsenic/isolation & purification/chemistry ; *Water Pollutants, Chemical/isolation & purification ; *Electrochemical Techniques/methods ; Water Purification/methods ; }, abstract = {Alum sludge (AlS) has emerged as an effective adsorbent for anionic contaminants, with traditional activation methods like acid/base treatments and calcination employed to enhance its adsorption capacity. However, these approaches encounter significant drawbacks, including excessive waste generation, structural degradation, and limited efficacy for cationic contaminants. To overcome these challenges, this study proposes electrochemical activation as a sustainable method to enhance alum sludge adsorption performance by generating oxygen-containing functional groups (O-FGs) on its surface. In particular, cathodic activated AlS (E-AlS) leads to the formation of hydroxyl (-OH) and carboxyl (-COOH) groups, which served as key active sites for Pb(II) adsorption through complexation mechanisms. E-AlS effectively removed both Pb(II) and As within 4 h, showcasing its dual functionality for cationic and anionic contaminants. While HCl- and KOH-activated AlS also achieved 100 % Pb(II) removal, they caused substantial aluminum (Al) leaching, exceeding 1,000 mg/L, due to structural instability. In contrast, E-AlS minimized Al leaching, preserved structural integrity, and exhibited a 6.5-fold higher Pb(II) adsorption capacity than raw AlS. X-ray photoelectron spectroscopy (XPS) and machine learning (ML) validated the enhanced adsorption performance of E-AlS. These findings highlight electrochemical activation as a cost-effective and environmentally friendly remediation.}, } @article {pmid40262277, year = {2025}, author = {Turner, N and Palmer, J and Faull, C and Davidson, S and Turner, MR and Wilson, E}, title = {Tracheostomy ventilation in ALS: healthcare practitioner perspectives on quality of life and implications for decision-making.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {26}, number = {5-6}, pages = {444-451}, doi = {10.1080/21678421.2025.2495014}, pmid = {40262277}, issn = {2167-9223}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/psychology/therapy ; *Quality of Life/psychology ; *Tracheostomy/psychology/methods ; Male ; Female ; *Decision Making ; *Health Personnel/psychology ; Qualitative Research ; Middle Aged ; *Attitude of Health Personnel ; *Respiration, Artificial/psychology/methods ; Adult ; }, abstract = {Objectives: This qualitative study aimed to increase understanding of how healthcare practitioners (HCPs) perceive quality of life for people with ALS who use tracheostomy ventilation (TV) and the extent to which such views inform discussions regarding future treatment and care. Methods: A thematic analysis was applied to data derived from online semi-structured interviews with a professionally diverse group of 24 HCPs with experience of supporting people with ALS to use TV. Results: Four main themes relating to TV use emerged: i) Positive benefits; ii) Risks and challenges; iii) Factors influencing HCP perspectives; iv) Concepts informing HCP discussions. HCPs acknowledged that TV has the potential to extend life but were concerned with prolonging a serious decline in physical and cognitive functioning. HCPs tried to identify the 'tipping point' between quantity and quality of life for the individual and their family, taking into account the likelihood of a higher burden of care. HCPs drew on prior experience to assess anticipated quality of life, yet most HCPs in the UK have limited experience of TV for this group. HCPs also drew on principles of person-centered care, patient autonomy and value for money to guide their approach to discussing TV. Conclusions: HCP experience of positive outcomes of TV can foster a more proactive approach to initiating conversations about its potential use. Sharing best practice and improving guidance for HCPs may support early and on-going future care planning and enable people with ALS to make choices which are informed and in their best interests.}, } @article {pmid40261626, year = {2025}, author = {Lum, JS and Brown, ML and Suters, SC and Yerbury, JJ and McAlary, L}, title = {In-Gel Zymography of Amyotrophic Lateral Sclerosis-Associated Variants of Superoxide Dismutase-1.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {2918}, number = {}, pages = {221-228}, pmid = {40261626}, issn = {1940-6029}, mesh = {*Amyotrophic Lateral Sclerosis/genetics/enzymology/metabolism ; *Superoxide Dismutase-1/genetics/metabolism ; Humans ; *Enzyme Assays/methods ; *Electrophoresis, Polyacrylamide Gel/methods ; }, abstract = {In-gel zymography allows the separation of protein via electrophoresis and subsequent measurement of enzymatic activity of enzymes from biological mixtures. The antioxidant enzyme superoxide dismutase 1 (SOD1) is an important cytosolic oxygen radical scavenging enzyme that has been implicated in a range of pathologies, including cancer, metabolic and neurodegenerative diseases, most notably amyotrophic lateral sclerosis (ALS). Here, we describe a method to detect and compare SOD1 activity from both cell and tissue samples. This method can be utilized to compare differences between ALS-associated SOD1 genetic variants and pharmacologically treated biological samples.}, } @article {pmid40261116, year = {2025}, author = {Shneider, NA and Nesta, AV and Rifai, OM and Yasek, J and Elyaman, W and Aziz-Zaman, S and Lyu, MA and Levy, SHS and Hoover, BN and Vlad, G and Huang, M and Zeng, K and Sadeghi, T and Reddy, A and Flowers, CR and Parmar, S}, title = {Clinical Safety and Preliminary Efficacy of Regulatory T Cells for ALS.}, journal = {NEJM evidence}, volume = {4}, number = {5}, pages = {EVIDoa2400249}, doi = {10.1056/EVIDoa2400249}, pmid = {40261116}, issn = {2766-5526}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy ; Middle Aged ; *T-Lymphocytes, Regulatory/transplantation ; Female ; Male ; Aged ; Adult ; Biomarkers/blood ; Treatment Outcome ; Neurofilament Proteins/blood ; }, abstract = {BACKGROUND: Peripheral and neuroinflammation have been previously associated with progression in amyotrophic lateral sclerosis (ALS), a neurodegenerative disease involving progressive loss of motor neurons. We hypothesize that regulatory T cell (Treg) therapy can resolve inflammation and preserve function in those patients with ALS.

METHODS: Participants with ALS received infusions of a fixed dose (100×10[6] cells) of umbilical cord blood-derived, allogeneic, nonhuman leukocyte antigen-matched, cryopreserved Treg product (TREG), administered as four weekly infusions followed by six monthly infusions. No lymphodepletion, immunosuppression, or interleukin 2 was administered. The primary outcome was dose-limiting toxicity, including infusion reaction within 24 hours (as graded by National Cancer Institute - Common Terminology Criteria for Adverse Events, Version 4.0) and/or regimen-related death, or grade 3 or 4 cytokine release syndrome within 14 days postinfusion. We measured clinical response using the Revised ALS Functional Rating Scale (ALSFRS-R; range 0 to 48, with lower numbers indicating lower functional ability). Exploratory analyses measured serum and plasma neurofilament light (NfL) and inflammatory biomarkers.

RESULTS: Six participants with a median age of 48.5 years (range 27 to 66 years) and baseline ALSFRS-R score of 31.5 (range 23 to 43) were treated with a median of 11 (range 6 to 22) TREG infusions in an ambulatory setting. No dose-limiting toxicity was observed. In participants with sufficient data points (n=4), the mean ALSFRS-R slope of decline was -1.66±1.03 points/month before treatment, -0.41±0.45/month during treatment, and -0.60±0.59/month posttreatment. Biomarkers including NfL and inflammatory markers MIP-1δ (macrophage inflammatory protein-1 delta), CTACK (cutaneous T cell-attracting chemokine), and GROα (growth-regulated oncogene alpha) exhibited different relationships with ALSFRS-R score between participants.

CONCLUSIONS: This study demonstrates the preliminary safety of "off-the-shelf", allogeneic Treg-cell therapy.}, } @article {pmid40741286, year = {2024}, author = {Garand, KLF and Malek, AM and Ambrocio, KR}, title = {Linking Oropharyngeal Swallowing Physiology and Functional Clinical Predictors in Amyotrophic Lateral Sclerosis.}, journal = {Perspectives of the ASHA special interest groups}, volume = {9}, number = {1}, pages = {282-291}, pmid = {40741286}, issn = {2381-4764}, support = {IK1 RX001628/RX/RRD VA/United States ; K24 DC012801/DC/NIDCD NIH HHS/United States ; TL1 TR000061/TR/NCATS NIH HHS/United States ; }, abstract = {PURPOSE: We aimed to quantify oropharyngeal swallowing physiology in amyotrophic lateral sclerosis (ALS) and examine relationships between swallowing impairments and ratings of pulmonary function (forced vital capacity percent predicted, FVC % pre) and functional status (ALS Functional Rating Scale-Revised, ALSFRS-R).

METHOD: A retrospective analysis of swallowing-related data of persons with ALS (PALS) was completed. Their Modified Barium Swallow Impairment Profile component, Oral Total (OT), and Pharyngeal Total (PT) scores were compared with data from age- (±1 year) and sex-matched healthy controls retrieved from an archival normative data set using Mann-Whitney U tests. Relationships between PALS' OT and PT scores, FVC % pre, and ALSFRS-R were examined using Pearson product-moment correlations and multiple linear regression modeling.

RESULTS: Twenty-one PALS (12 women), with a mean age of 62.2 ± 9.9 years, were included in the analyses. Compared to healthy controls, PALS exhibited significantly worse function across 13 (76%) physiological swallowing components (all p < .05). OT and PT scores significantly differed between PALS and healthy controls (each p < .001), with higher scores (worse impairment) observed in the former. When adjusting for age and sex, FVC % pre was a significant predictor of OT score (p = .045). An inverse relationship was found with ALSFRS-R and OT score (p = .052). FVC % pre (p = .061) and ALSFRS-R (p = .54) did not significantly predict PT score.

CONCLUSIONS: PALS demonstrated swallowing impairments across oropharyngeal domains and the esophageal component. In our PALS cohort, FVC % pre was a useful clinical indicator of oral swallowing impairment.}, } @article {pmid40395512, year = {2024}, author = {Tanaka, Y and Ito, SI and Suzuki, G}, title = {TDP-43 Secretion via Extracellular Vesicles Is Regulated by Macroautophagy.}, journal = {Autophagy reports}, volume = {3}, number = {1}, pages = {2291250}, pmid = {40395512}, issn = {2769-4127}, abstract = {The pathological accumulation of the nuclear protein TDP-43 (TAR DNA-binding protein 43 kDa) in the cytoplasm is characteristic of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD-TDP), and its spread through the brain and spinal cord is closely associated with the progression of these two diseases. However, the mechanisms through which the TDP-43 pathology propagates throughout the central nervous system remain unclear. We recently reported the role of (macro)autophagy in the secretion of TDP-43 via extracellular vesicles (EVs). We found that among the autophagy modulators, bafilomycin A1 (Baf) and GRN (granulin precursor) deficiency impair the formation of autolysosomes and promote the secretion of TDP-43 by EVs. TDP-43 loading on EVs involves autophagy-related proteins and the knockdown of TDP-43 augmented Baf-induced EV release. Thus, our results suggest that the loss-of-function of TDP-43 accelerates release of EVs possibly derived from autophagosomes, which may mediate cell-to-cell spread of the TDP-43 pathology.}, } @article {pmid40655970, year = {2023}, author = {Vardheim, EG and Toft, A and Nielsen, JE and Hasselbalch, SG and Simonsen, AH}, title = {Cerebrospinal fluid ubiquitin as a biomarker for neurodegenerative diseases: A systematic review.}, journal = {Neuroscience applied}, volume = {2}, number = {}, pages = {102438}, pmid = {40655970}, issn = {2772-4085}, abstract = {Ubiquitin plays a vital role in neuronal proteostasis, as a major but often overlooked component of neurotoxic protein aggregates across neurodegenerative diseases. Although neuropathological changes can be present for years before clinical onset, early and accurate diagnosis remains an immense challenge in this disease category. The level of ubiquitin in cerebrospinal fluid (CSF) has been assessed as a biomarker for several disease entities. This systematic review compares current findings and evaluates the potential of CSF ubiquitin as a fluid biomarker. A systematic literature search identified studies comparing CSF ubiquitin levels between a control group and patients with one of the following diseases: Alzheimer's disease (AD), Parkinson's disease (PD), frontotemporal dementia (FTD), Lewy body dementia (DLB), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS). All included studies were reviewed systematically by two independent authors. 171 studies were identified. A total of 17 studies met the eligibility criteria and were included. Nine out of 13 studies found a significant increase of CSF ubiquitin in AD patients compared with control groups. Correlations between CSF ubiquitin and other established biomarkers were demonstrated in seven studies. A single study was included for both HD and DLB respectively, each showing significantly higher CSF ubiquitin in patients compared to controls. In patients with PD, FTD or ALS, CSF ubiquitin levels were generally equal to those of the control groups, with two studies showing significantly decreased concentrations in a PD and an FTD cohort. Presently, the available body of research is insufficient to assess whether CSF ubiquitin could contribute to the clinical setting, alongside established markers of neurodegeneration. The correlation of elevated CSF ubiquitin with AD is well-founded, whilst validation of reduced or unchanged levels in the other neurodegenerative diseases will determine the usefulness of the biomarker in clinical practice.}, } @article {pmid40395318, year = {2023}, author = {Sun, S and Wang, H and Ma, Q and Li, N and Cao, M and Tam, KY and Ying, Z}, title = {PRKN regulates inner mitochondrial membrane PHB2 during mitophagy.}, journal = {Autophagy reports}, volume = {2}, number = {1}, pages = {2164643}, pmid = {40395318}, issn = {2769-4127}, abstract = {PINK1 (PTEN induced kinase 1) and PRKN-mediated mitophagy is an important mitochondrial quality control pathway which selectively degrades damaged mitochondria and is tightly associated with neurodegenerative diseases, including Parkinson disease and amyotrophic lateral sclerosis. The current model of PINK1-PRKN-mediated mitophagy is that PRKN ubiquitinates multiple outer mitochondrial membrane (OMM) proteins, and then the ubiquitin chains on the OMM interact with autophagy receptors which bind Atg8-family protein labeled phagophores. However, little work has been focused on the PRKN-mediated ubiquitination of inner mitochondrial membrane (IMM) proteins during mitophagy. Our recent work revealed that PRKN binds and ubiquitinates PHB2 (prohibitin 2), an essential IMM protein which was previously recognized as a mitophagy receptor, after the OMM is ruptured by proteasomal degradation. Using biochemical and microscopy approaches, we found that mutations of PRKN-targeted ubiquitination sites on PHB2 decrease the recognition of damaged mitochondria by the phagophore and the clearance of damaged mitochondria. In conclusion, our findings revealed a critical role for PRKN-PHB2 interaction in mitochondrial quality control by regulating IMM-associated recognition of mitochondria by the autophagy machinery.}, } @article {pmid40396030, year = {2022}, author = {Ichimura, Y and Komatsu, M}, title = {Considering the mechanism by which droplets of ALS-FTD-associated SQSTM1/p62 mutants cause pathology.}, journal = {Autophagy reports}, volume = {1}, number = {1}, pages = {9-13}, pmid = {40396030}, issn = {2769-4127}, abstract = {Large numbers of point mutations in SQSTM1/p62 have been identified in amyotrophic lateral sclerosis (ALS) and frontotemporal degeneration (FTD). SQSTM1 interacts with ubiquitinated proteins, undergoing liquid-liquid phase separation, and the resulting SQSTM1-droplets are degraded by macroautophagy/autophagy. SQSTM1 also serves as a multiple signaling hub for processes including selective autophagy and the anti-oxidative stress response. Such diverse functions are modulated by multiple domains and regions throughout the protein. Because mutations in SQSTM1 have been identified throughout its gene, including regions encoding the domains and motifs, the effects of these mutations on disease onset have been thought to be complicated. Recently, we thoroughly investigated how 7 mutations around the LC3-interacting region and KEAP1-interacting region (amino acids 335-356) affected autophagic degradation of SQSTM1, the anti-oxidative stress response, the KEAP1-NFE2L2/Nrf2 pathway, and the dynamics of SQSTM1 droplets. We found that reduced inner fluidity of the droplets is a unique, shared defect among all mutants, suggesting a link between qualitative changes in SQSTM1 liquid droplets and ALS-FTD. In this punctum article, we discuss the mechanism whereby reduced inner fluidity of mutant SQSTM1 droplets causes ALS-FTD pathology.}, } @article {pmid40261114, year = {2025}, author = {Abati, E}, title = {Regulatory T Cell-Based Therapies - A New Piece of the ALS Therapeutic Puzzle?.}, journal = {NEJM evidence}, volume = {4}, number = {5}, pages = {EVIDe2500078}, doi = {10.1056/EVIDe2500078}, pmid = {40261114}, issn = {2766-5526}, } @article {pmid40260525, year = {2025}, author = {Ganapule, A and Garg, D and Agarwal, A and Gupta, A and Rajan, R and Desai, S and Chandarana, M and Sidharth, S and Tripathi, M and Garg, A and Radhakrishnan, DM and Srivastava, AK}, title = {The Expanding Spectrum of Anti-IgLON5 Disease: A Case Series from an Indian Cohort.}, journal = {Annals of Indian Academy of Neurology}, volume = {28}, number = {3}, pages = {440-444}, pmid = {40260525}, issn = {0972-2327}, abstract = {Anti-IgLON5 disease is an evolving entity that lies at the confluence of autoimmunity and neurodegeneration. Reports from India remain sparse. In this series, we describe seven Indian patients with anti-IgLON5-related disease. Patients presented across the fifth to eighth decades with a mean duration of illness of 16 months. All had movement disorders, which included gait ataxia, parkinsonism, and chorea. Six patients had sleep disturbances. Five had a frontal dysexecutive dementia phenotype. Two had epilepsy. Bulbar involvement was present in four, and one had amyotrophic lateral sclerosis (ALS)-like features. Magnetic resonance imaging was abnormal in two cases. Positron emission tomography of the brain also contributed to diagnosis. Combination immunotherapies were used in most of the patients, with three showing a sustained response and two deaths reported due to sepsis-related complications. It is important to recognize the increasing spectrum of IgLON5-related disease to enable timely initiation of immunotherapy before marked degeneration occurs.}, } @article {pmid40260387, year = {2025}, author = {Guo, N and Huang, W and Huang, J and Liu, Y and Zhu, K and Gao, W}, title = {Global research trends in biomarkers, therapeutic targets, and drugs for amyotrophic lateral sclerosis: a bibliometric and visualization analysis.}, journal = {Frontiers in pharmacology}, volume = {16}, number = {}, pages = {1588968}, pmid = {40260387}, issn = {1663-9812}, abstract = {BACKGROUND: Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive degeneration of motor neurons, marked by complex pathological mechanisms and a lack of effective treatments. Despite substantial global research efforts, no comprehensive bibliometric analysis has systematically mapped the evolution of ALS biomarkers, therapeutic targets, and pharmacological advancements.

METHODS: This study, based on 4,250 publications retrieved from the Web of Science Core Collection (2005-2025), employs bibliometric tools such as CiteSpace and VOSviewer to conduct the first multidimensional analysis of global trends in ALS biomarkers, therapeutic targets, and drug research.

RESULTS: The results revealed contributions from 20,168 authors across 92 countries, with annual publications growing at an average rate of 16.5%. The United States dominated research output, accounting for 34.07% (n=1,448, TLCS=7,100), while the United Kingdom achieved the highest research impact with an average of 68 citations per article. Leading institutions, including the University of Oxford and the University of Milan, consistently produced high-impact studies. Pioneering scholars such as Turner MR and Kiernan MC made significant contributions to advancing therapeutic targets and drug discovery. The interdisciplinary integration of molecular biology and genetics emerged as a core driver of progress in ALS research. Neurofilament light chain (NfL), antisense oligonucleotide (ASO) drugs, transcranial magnetic stimulation (TMS), oxygen free radicals (oxidative stress), and gene therapy have consistently remained central research focuses in the ALS therapeutic field. Looking ahead, stem cell therapy, blood-brain barrier (BBB) penetration technologies, and skeletal muscle targeting are poised to emerge as prominent research directions.

CONCLUSION: The United States dominates ALS research productivity, whereas the United Kingdom demonstrates superior citation influence. Despite China's substantial publication volume, its limited citation impact underscores the necessity for enhanced methodological rigor and strategic international collaboration. Current research priorities encompass NfL, TMS, and ASO therapies, with emerging innovations in stem cell therapy, BBB penetration technologies and skeletal muscle targeting showing therapeutic promise. Future directions should prioritize biomarker standardization, optimization of drug delivery systems, and Clinical Translation.}, } @article {pmid40259632, year = {2025}, author = {García-Casanova, PH and Pérez-Martínez, P and Sevilla, T and Doménech, R and León, M and Vázquez-Costa, JF}, title = {In Response to "Homogeneous ALS Cohorts in Terms of Etiology, Onset Type and Vaccination Status Are Required to Assess the Outcome of Their COVID Infection".}, journal = {European journal of neurology}, volume = {32}, number = {4}, pages = {e70162}, pmid = {40259632}, issn = {1468-1331}, } @article {pmid40259624, year = {2025}, author = {Finsterer, J}, title = {Homogeneous ALS Cohorts in Terms of Etiology, onset type, and Vaccination Status Are Required to Assess the Outcome of Their COVID Infection.}, journal = {European journal of neurology}, volume = {32}, number = {4}, pages = {e70161}, pmid = {40259624}, issn = {1468-1331}, } @article {pmid40258293, year = {2025}, author = {Elsayyid, M and Tanis, JE and Yu, Y}, title = {Simple In-Cell Processing Enables Deep Proteome Analysis of Low-Input Caenorhabditis elegans.}, journal = {Analytical chemistry}, volume = {97}, number = {17}, pages = {9159-9167}, pmid = {40258293}, issn = {1520-6882}, support = {T32 GM133395/GM/NIGMS NIH HHS/United States ; R01 GM135433/GM/NIGMS NIH HHS/United States ; P20 GM103446/GM/NIGMS NIH HHS/United States ; S10 OD030321/OD/NIH HHS/United States ; P20 GM139760/GM/NIGMS NIH HHS/United States ; P20 GM104316/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; *Caenorhabditis elegans/metabolism/chemistry ; *Proteome/analysis ; *Caenorhabditis elegans Proteins/analysis/metabolism ; *Proteomics/methods ; Chromatography, Liquid ; Superoxide Dismutase-1/genetics/metabolism ; }, abstract = {Caenorhabditis elegans is a widely used genetic model organism; however, the worm cuticle complicates extraction of intracellular proteins, a prerequisite for typical bottom-up proteomics. Conventional physical disruption procedures are not only time-consuming but can also cause significant sample loss, making it difficult to perform proteomics with low-input samples. Here, for the first time, we present an on-filter in-cell (OFIC) processing approach that can digest C. elegans proteins directly in the cells of the organism after methanol fixation. With OFIC processing and single-shot LC-MS analysis, we identified over 9400 proteins from a sample of only 200 worms, the largest C. elegans proteome reported to date that did not require fractionation or enrichment. We systematically evaluated the performance of the OFIC approach by comparing it to conventional lysis-based methods. Our data suggest superior performance of OFIC processing for C. elegans proteome identification and quantitation. We further evaluated the OFIC approach with even lower-input samples, including single worms. Then, we used this method to determine how the proteome is impacted by loss of superoxide dismutase sod-1, the ortholog of human SOD1, a gene associated with amyotrophic lateral sclerosis. Analysis of 8800 proteins from only 50 worms as the initial input showed that loss of sod-1 affects the abundance of proteins required for stress response, ribosome biogenesis, and metabolism. In conclusion, our streamlined OFIC approach, which can be broadly applied to other systems, minimizes sample loss while offering the simplest workflow reported to date for C. elegans proteomics.}, } @article {pmid40256588, year = {2024}, author = {Ahmady, H and Afrand, M and Motaqi, M and Meftahi, GH}, title = {Utilizing Sertoli Cell Transplantation as a Therapeutic Technique for the Management of Neurodegenerative Diseases.}, journal = {Archives of Razi Institute}, volume = {79}, number = {4}, pages = {701-710}, pmid = {40256588}, issn = {2008-9872}, mesh = {*Neurodegenerative Diseases/therapy ; Humans ; Male ; Animals ; *Sertoli Cells/transplantation ; }, abstract = {Neurodegenerative diseases (NDs), such as Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD), are defined by aberrant protein accumulation, brain atrophy, and gradual decline of neuronal function. Despite the considerable endeavors devoted to discovering treatments for NDs in recent decades, the demand for efficient therapeutic agents persists. Sertoli cells (SCs) play a crucial role in providing a supportive structure and environment for the development of germ cells. SCs, whether transplanted as xenogeneic or allogeneic cells, present a viable choice for enhancing graft persistence via the release of immunomodulatory and trophic factors, including neurturin (NTN), platelet-derived growth factor, Fas (CD95) ligand (FasL), glial-derived neurotrophic factor, interleukin 1 (IL1), brain-derived neurotrophic factor, interleukin 6 (IL6), transforming growth factors, and vascular growth factor, that protect replaced cells and tissues from the immune system. However, there is currently no cohesive evidence regarding the neuroprotective influence of the transplantation of SCs on NDs. Therefore, this review focuses on assessing stem cells' neuroprotective impact on neurodegenerative diseases in pre-clinical settings and presenting cohesive information. A comprehensive search was conducted between 2000 and 2022. In the identification stage, after a comprehensive search across databases, including Web of Science, Scopus, and PubMed/Medline, 103 papers were obtained. The search conducted in the present study yielded a total of nine relevant papers on the therapeutic effect of the transplantation of SCs on NDs. It was found that the transplantation of SCs exhibits a promising impact on enhancing the symptoms of neurological diseases in rats. The findings highlight the need for multiple standardized pre-clinical trials to find reliable information to confirm the utilization of the transplantation of SCs and the reduction of the symptoms of neurodegenerative diseases.}, } @article {pmid40255098, year = {2025}, author = {Regnault, R and Kouach, M and Goossens, L and Thuru, X and Bailly, C and Goossens, JF}, title = {HR-MS Analysis of the Covalent Binding of Edaravone to 5-Formylpyrimidine Bases and a DNA Oligonucleotide Containing a 5-Formylcytidine Residue.}, journal = {Rapid communications in mass spectrometry : RCM}, volume = {39}, number = {14}, pages = {e10050}, pmid = {40255098}, issn = {1097-0231}, support = {//Comité de l'Oise de la Ligue Contre le Cancer/ ; //French Ligue Against Cancer/ ; }, mesh = {Edaravone/chemistry ; *Mass Spectrometry/methods ; *Oligonucleotides/chemistry/metabolism ; *Pyrimidines/chemistry ; *DNA/chemistry ; *Cytidine/chemistry/analogs & derivatives ; Cytosine/analogs & derivatives ; }, abstract = {RATIONALE: Edaravone (EDA) is a radical scavenger and an antioxidant drug approved to treat amyotrophic lateral sclerosis and used as a research tool to explore treatment of neurodegenerative diseases and cancers. It is also a reactive agent, known as PMP (1-phenyl-3-methyl-5-pyrazolone), used for the analysis of polysaccharides composition. EDA can react with sugars and aromatic aldehydes. In this context, we have investigated the reactivity of EDA toward the biologically relevant formylated nucleobases, nucleosides, and an oligonucleotide containing a formylated residue.

METHODS: The formation of both mono- and bis-adducts between EDA and the formylated nucleobases (5-formyluracil (5fU) and 5-formylcytosine (5fC)) or the corresponding nucleosides 5-fdU and 5-fdC was characterized using high-resolution mass spectrometry (HR-MS). Similarly, the covalent binding of EDA to an 8-mer palindromic oligonucleotide d (TATG[*C]ATA) containing a single 5-fdC residue [*C] under physiological conditions was investigated using mass spectrometry.

RESULTS: For the first time, EDA is shown to react with formylated pyrimidines. Covalent and stable adducts were identified. EDA was found to react efficiently with the formylated oligonucleotide to generate mono- and bis-adducts. The rate of formation of the mono-adduct was five times higher than that of the bis-adduct. The reaction of EDA with aldehydic DNA modifications such as 5fU/5fC may have important consequences in terms of gene expression.

CONCLUSIONS: These observations raise implications for an epigenetic contribution to the mechanism of action of EDA. The biological implications of our in vitro results are discussed, notably in the frame of neurodegenerative diseases and cancers.}, } @article {pmid40254405, year = {2025}, author = {Shevchuk, DV and Tukhvatulin, AI and Dzharullaeva, AS and Berdalina, IA and Zakharova, MN}, title = {Molecular Biomarkers of Neurodegeneration in Amyotrophic Lateral Sclerosis.}, journal = {Biochemistry. Biokhimiia}, volume = {90}, number = {2}, pages = {276-288}, doi = {10.1134/S0006297924604039}, pmid = {40254405}, issn = {1608-3040}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism/diagnosis/pathology/blood ; Biomarkers/metabolism/blood ; Male ; Female ; Middle Aged ; Aged ; Amyloid beta-Peptides/metabolism/blood ; Adult ; tau Proteins/metabolism/blood ; Clusterin ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is the most prevalent motor neuron disease. However, definitive diagnosis could be delayed by up to 12 months due to the lack of specific and sensitive biomarkers for ALS. In our study, conducted for the first time on a large cohort of ALS patients (n = 100) within the Russian population, we assessed key biomarkers of neurodegenerative pathology, including β-amyloids (Aβ40 and Aβ42) and tau proteins (Tau-total and Tau-p181), as well as other pathogenetically relevant, promising biomarkers such as FGF-21, Kallikrein-6 (KLK-6), NCAM-1, Neurogranin (NRGN), TDP-43, Apolipoprotein E4, Clusterin (Apo J), Complement Factor H, Fetuin-A, α2-Macroglobulin, Apo AI, Apo CIII, Apo E, Complement C3, GDNF, sRAGE, and S100B protein. Significant differences between the ALS patients and the control group were observed for Aβ40 (p = 0.044), Aβ42 (p < 0.001), FGF-21 (p < 0.001), Tau-total (p = 0.001), Tau-p181 (p = 0.014), Clusterin (p < 0.001), Complement C3 (p = 0.001), and S100B (p = 0.024). A significant direct correlation was found between the ALSFRS-R score and concentrations of Aβ40 and Aβ42. Changes in the complement system (Complement C3 and Complement Factor H) were identified, highlighting critical role of neuroinflammatory processes in ALS pathogenesis. Additionally, increased levels of FGF-21 were observed in the patients with the bulbar onset of ALS. Significant increase in the concentration of the chaperone protein clusterin in the patients with rapid disease progression suggests its potential as a prognostic biomarker for motor neuron disease. Furthermore, its role in maintaining proteostasis could provide novel therapeutic targets.}, } @article {pmid40254295, year = {2025}, author = {Epel, ES and White, KE and Brownell, KD and Rodin, J and Hollis, AL and Diefenbach, MA and Alegria, KE and Fromer, E and Czajkowski, SM and Bacon, SL and Revenson, TA and Ruiz, J and Maibach, E and , }, title = {Transforming Health Psychology and Behavioral Medicine to Address the Climate Crisis: A Call for Strategic Research and Advocacy.}, journal = {Annals of behavioral medicine : a publication of the Society of Behavioral Medicine}, volume = {59}, number = {1}, pages = {}, doi = {10.1093/abm/kaae088}, pmid = {40254295}, issn = {1532-4796}, mesh = {Humans ; *Climate Change ; *Behavioral Medicine ; *Health Behavior ; Social Change ; }, abstract = {OBJECTIVE: The climate crisis poses the largest threat to human health and survival and has been a public health emergency for many years. It is causing harmful consequences for physical and mental health and is amplifying existing health inequities. In this call to action, we highlight the relevance of the health psychology and behavioral medicine communities in addressing the health impacts of climate change.

METHOD: We identify mitigation and adaptation climate health behaviors and social changes needed that underlie the three essential objectives to address climate change and its associated health consequences: (a) rapid decarbonization, (b) drawdown of atmospheric heat-trapping gases (sequestration), and (c) adap- tation.

RESULTS: To advance the behavioral and systemic changes necessary to protect health, we propose a 1-2-3 Transformational Model in which the larger field of health psychology and behavioral medicine promotes (1) One Health, human and planetary health by (2) targeting climate health behaviors, and (3) social change across major professional areas, including research, interventions, and education/advo- cacy. We urge the adoption of the social quantum change paradigm, a systems approach to understanding the process of social change, where systemic change is viewed as local to global, and the individual has an influential role.

DISCUSSION: These shifts in views, priorities, and methods will bolster hope, collective efficacy, and action to support the next generation of health psychology and behavioral medicine profession- als. With these changes, the health psychology and behavioral medicine communities can have a more immediate and meaningful impact on the climate crisis and its associated health consequences.}, } @article {pmid40254133, year = {2025}, author = {Turner-Ivey, B and Jenkins, DP and Carroll, SL}, title = {Multiple Roles for Neuregulins and Their ERBB Receptors in Neurodegenerative Disease Pathogenesis and Therapy.}, journal = {The American journal of pathology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ajpath.2025.03.012}, pmid = {40254133}, issn = {1525-2191}, abstract = {The role that neurotrophins, such as nerve growth factor, play in the pathogenesis of neurodegenerative diseases has long been appreciated. However, the neuregulin (NRG) family of growth factors and/or their v-erb-B2 avian erythroblastic leukemia viral oncogene homolog (ERBB) receptors have also been implicated in the pathogenesis of conditions, such as Alzheimer disease (AD), frontotemporal lobar degeneration (FTLD), and amyotrophic lateral sclerosis (ALS). In this review, we consider i) the structural variability of NRG isoforms generated by alternative RNA splicing, the use of multiple promoters and proteolysis, and the impact that this structural variability has on neuronal and glial physiology during development and adulthood. We discuss ii) the NRG receptors ERBB2, ERBB3, and ERBB4, how activation of each of these receptors further diversifies NRG actions in the central nervous system, and how dementia-related proteins, such as γ-secretase modulate the action of NRGs and their ERBB receptors. We then iii) turn to the abnormalities in NRG and ERBB expression and function evident in human AD and mouse AD models, how these abnormalities affect brain function, and attempts to use NRGs to treat AD. Finally, iv) we discuss NRG effects on the survival and function of neurons relevant to FTLD and ALS, alterations in NRG/ERBB signaling identified in these conditions, and the recent discovery of multiple human pedigrees in which autosomal dominant FTLD/ALS potentially results from point mutations in ERBB4.}, } @article {pmid40253599, year = {2025}, author = {Malik, M and Bhatti, T and Hodson-Tole, E and Onambele-Pearson, G and Chaouch, A}, title = {Physical activity in amyotrophic lateral sclerosis: a systematic review of the methodologies used to assess a possible association.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {}, number = {}, pages = {1-18}, doi = {10.1080/21678421.2025.2488298}, pmid = {40253599}, issn = {2167-9223}, abstract = {Growing evidence suggests that strenuous physical activity (PA) may be associated with an increased risk of developing Amyotrophic Lateral Sclerosis (ALS), a fatal neurodegenerative disease. However, there are inconsistent findings across studies that may reduce our understanding of any potential associations. We propose that these differences may reflect the tools used to record historical PA. We conducted a systematic review evaluating the risk of developing ALS due to PA. The inclusion criteria were met by 22/113 studies, and an association between increasing PA and ALS was found in 15 studies. Studies that found a positive association were more likely to have longer recall periods and convert data into Metabolic Equivalent of Task values. Studies that did not find an association with increasing PA were more likely to use questionnaires with no validity or reliability data. Questionnaires with validity data all showed at least a moderate correlation of PA compared to objective measures, with reliability ranging from poor to good. Study designs included prospective cohort and case-control, which may also contribute to heterogeneity in findings. This work highlights the need for consensus on the type of questionnaire to use to assess potential associations between PA and ALS.}, } @article {pmid40252901, year = {2025}, author = {Baidya, AT and Dante, D and Das, B and Wang, L and Darreh-Shori, T and Kumar, R}, title = {Discovery and characterization of novel pyridone and furan substituted ligands of choline acetyltransferase.}, journal = {European journal of pharmacology}, volume = {998}, number = {}, pages = {177638}, doi = {10.1016/j.ejphar.2025.177638}, pmid = {40252901}, issn = {1879-0712}, mesh = {*Choline O-Acetyltransferase/metabolism/antagonists & inhibitors/chemistry ; Humans ; Ligands ; *Furans/chemistry/pharmacology/metabolism ; Molecular Dynamics Simulation ; *Drug Discovery ; *Pyridones/chemistry/pharmacology/metabolism ; Molecular Docking Simulation ; *Enzyme Inhibitors/pharmacology/chemistry/metabolism ; Structure-Activity Relationship ; Animals ; }, abstract = {The key to the management of two devastating diseases, namely Alzheimer's Disease (AD) and Amyotrophic Lateral Sclerosis (ALS) lies in an early diagnosis, which is difficult due to its multifactorial nature. However, a common hallmark of AD and ALS is degeneration of cholinergic system. Choline acetyltransferase (ChAT) has been proposed as a potential target for development of cholinergic-specific biomarker. However, lack of selective, potent, brain permeable molecular probes of ChAT hinder development of ChAT biomarkers. In this study, we have successfully utilised structure-based virtual screening approach and identified two ChAT inhibitors from a database of 1.4 million compounds. The compounds were then subjected to rigorous in vitro characterization. Compound V6 showed Ki value of 11 μM and IC50 value of 21.73 μM, while V15 showed Ki and IC50 values of 4.5 and 9.42 μM, respectively for ChAT enzyme. V6 and V15 showed good solubility of 0.21 mg/mL and 0.17 mg/mL respectively and cytotoxicity analysis indicated no toxicity. We also performed a 200 ns molecular dynamics simulation, which revealed the intricate interaction dynamics for V6 and V15 with ChAT binding pocket. Moreover, the Tanimoto similarity analysis indicated the novelty and structural diversity of the hits. In conclusion, these validated hits provide a platform to develop potent, selective, blood-brain barrier permeable small molecules as chemical probes of ChAT or as Positron Emission Tomography tracer for early diagnosis and/or in vivo monitoring of the effect of new therapeutic candidates in spectrum of neurodegenerative disorders, in which cholinergic deficit is one of the hallmarks.}, } @article {pmid40252655, year = {2025}, author = {Dame, PS}, title = {The four most common genetic subtypes of amyotrophic lateral sclerosis: state of the art and future directions.}, journal = {The Lancet. Neurology}, volume = {24}, number = {5}, pages = {380-381}, doi = {10.1016/S1474-4422(25)00117-6}, pmid = {40252655}, issn = {1474-4465}, } @article {pmid40251832, year = {2025}, author = {Bresque, M and Esteve, D and Balmer, G and Hamilton, HL and Stephany, JS and Pehar, M and Vargas, MR}, title = {FABP7 Expression Modulates the Response of Astrocytes to Induced Endotoxemia.}, journal = {Glia}, volume = {73}, number = {8}, pages = {1627-1641}, pmid = {40251832}, issn = {1098-1136}, support = {R01 NS122973/NS/NINDS NIH HHS/United States ; R01 NS132760/NS/NINDS NIH HHS/United States ; R01NS132760/NH/NIH HHS/United States ; R01NS122973/NH/NIH HHS/United States ; }, mesh = {*Astrocytes/metabolism/drug effects ; Animals ; *Fatty Acid-Binding Protein 7/metabolism/genetics ; Mice ; Humans ; *Endotoxemia/metabolism/chemically induced ; Lipopolysaccharides/toxicity ; Cells, Cultured ; Mice, Inbred C57BL ; Male ; Coculture Techniques ; Tumor Suppressor Proteins ; }, abstract = {Fatty acid binding proteins (FABPs) are a family of small proteins involved in fatty acid (FA) subcellular trafficking. In the adult central nervous system, FABP7, one of the members of this family, is highly expressed in astrocytes and participates in lipid metabolism, regulation of gene expression, and energy homeostasis. Reactive astrocytes in Alzheimer's disease and amyotrophic lateral sclerosis animal models upregulate FABP7 expression. This upregulation may contribute to the pro-inflammatory phenotype that astrocytes display during neurodegeneration and is detrimental for co-cultured neurons. Here, we explore how FABP7 expression modulates astrocyte response to inflammatory stimuli. Our results showed that silencing FABP7 expression in astrocyte cultures before treatment with different inflammatory stimuli decreases the expression of a luciferase reporter expressed under the control of NF-κB -response elements. Correspondingly, FABP7-silenced astrocytes display decreased nuclear translocation of the NF-κB-p65 subunit in response to these stimuli. Moreover, silencing FABP7 decreases the toxicity of stimulated astrocytes toward co-cultured motor neurons. Similar results were obtained after silencing FABP7 in human astrocytes differentiated from induced pluripotent stem cells. Finally, knockdown of astrocytic FABP7 expression in vivo reduces glial activation in the cerebral cortex of mice after systemic bacterial lipopolysaccharide (LPS) administration. In addition, whole transcriptome RNA sequencing analysis from the cerebral cortex of LPS-treated mice showed a differential inflammatory transcriptional profile, with attenuation of NF-κB-dependent transcriptional response after FABP7 knockdown. Together, our results highlight the potential of FABP7 as a target to modulate neuroinflammation in the central nervous system.}, } @article {pmid40251218, year = {2025}, author = {Abid, MN and Siming, L and Chao, H and Amin, M and Sarwer, S}, title = {Enhancing faculty teaching performance through constructive leadership with a mediating role of job satisfaction.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {13454}, pmid = {40251218}, issn = {2045-2322}, mesh = {*Job Satisfaction ; *Leadership ; Humans ; Male ; Female ; Cross-Sectional Studies ; *Teaching ; Adult ; *Faculty/psychology ; Universities ; Pakistan ; Middle Aged ; Surveys and Questionnaires ; }, abstract = {This study explored the impact of constructive leadership styles including transformational leadership (TLS), authentic leadership (ALS), and servant leadership (SLS) on faculty teaching performance (FTP), with job satisfaction (JS) acting as a critical mediator. Using a cross-sectional design and convenience sampling, data were collected from 346 faculty members across six universities in Lahore, Pakistan. Structural equation modeling (SEM) and regression analysis revealed that all three leadership styles significantly enhanced FTP, with transformational leadership showing the strongest influence. Authentic and servant leadership also demonstrated robust positive effects. Job satisfaction emerged as a pivotal mediator, strengthening the relationship between CLS and FTP.These findings highlight the transformative potential of constructive leadership in improving teaching performance and emphasize the critical role of department heads in fostering such practices. By prioritizing strategies to enhance employee motivation and satisfaction, institutions can improve retention, productivity, and overall academic excellence. This study reinforces existing literature on leadership and teaching performance while providing novel insights into the mediating role of job satisfaction, offering actionable implications for academic leadership and organizational development.}, } @article {pmid40250284, year = {2025}, author = {Calma, AD and Pavey, N and Silva, CS and van den Bos, MAJ and Yiannikas, C and Farrar, MA and Kiernan, MC and Menon, P and Vucic, S}, title = {Diagnostic utility of threshold tracking TMS paradigms in early amyotrophic lateral sclerosis.}, journal = {Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology}, volume = {174}, number = {}, pages = {105-113}, doi = {10.1016/j.clinph.2025.03.044}, pmid = {40250284}, issn = {1872-8952}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/physiopathology ; *Transcranial Magnetic Stimulation/methods ; Male ; Female ; Middle Aged ; Aged ; *Evoked Potentials, Motor/physiology ; Adult ; Motor Cortex/physiopathology ; Prospective Studies ; }, abstract = {OBJECTIVE: Threshold tracking transcranial magnetic stimulation (TMS) has exhibited utility as a diagnostic technique in Amyotrophic Lateral Sclerosis (ALS). Different threshold tracking paradigms have recently been proposed. The present study assessed the diagnostic utility of serial ascending and parallel threshold tracking TMS in ALS.

METHODS: Threshold tracking TMS was undertaken on 90 prospectively recruited participants suspected of ALS. Short interval intracortical inhibition (SICI) was recorded with serial ascending and parallel threshold tracking paradigms between Interstimulus Interval (ISI) 1-to-7 ms. The primary outcome measure was differences in diagnostic utility of the paradigms in differentiating ALS from ALS mimicking disorders using receiver operating characteristic (ROC) analysis (DeLong statistical method).

RESULTS: Reduction in SICI reliably differentiated ALS from mimic disorders, irrespective of the threshold tracking paradigm. Comparison of area under the curve (AUC) established a significantly higher value for mean SICI (1-7 ms) with the serial ascending SICI paradigm (0.81, 95 % confidence interval 0.72-0.91) compared to the parallel paradigm (SICI 0.72, 95 % confidence interval 0.61-0.83, p = 0.0065). The better diagnostic utility of serial ascending paradigm was evident for SICI recorded between 1-to-5 ms, and was maintained irrespective of disease onset site, degree of functional impairment, and the degree of lower motor neuron dysfunction. A comparable diagnostic utility across threshold tracking paradigms was evident in ALS participants who presented with a relative paucity of upper motor neuron signs.

CONCLUSION: While threshold tracking TMS reliably differentiated ALS from mimic disorders, the present study established better diagnostic utility with the serial ascending threshold tracking TMS paradigm.

SIGNIFICANCE: The serial ascending threshold tracking TMS should be used in a clinical setting as a diagnostic tool for ALS.}, } @article {pmid40250093, year = {2025}, author = {Casiraghi, V and Pellegrini, E and Brusati, A and Peverelli, S and Invernizzi, S and Santangelo, S and Colombrita, C and Verde, F and Ticozzi, N and Silani, V and Ratti, A}, title = {Characterization of human healthy i[3] lower motor neurons exposed to CSF from ALS patients stratified by UNC13A and C9ORF72 genotype.}, journal = {Journal of the neurological sciences}, volume = {473}, number = {}, pages = {123508}, doi = {10.1016/j.jns.2025.123508}, pmid = {40250093}, issn = {1878-5883}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/cerebrospinal fluid/genetics/pathology ; *C9orf72 Protein/genetics ; *Motor Neurons/drug effects/metabolism/pathology ; Induced Pluripotent Stem Cells ; *Nerve Tissue Proteins/genetics ; Male ; Genotype ; Female ; Polymorphism, Single Nucleotide/genetics ; Middle Aged ; Aged ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease affecting upper and lower motor neurons. Neurodegeneration in ALS might be driven by proteotoxicity or neuroinflammation, which have also been proposed to be promoted by toxic components of the cerebrospinal fluid (CSF). We investigated the possible toxicity of ALS CSF on healthy induced pluripotent stem cells (iPSC)-derived integrated, inducible, and isogenic lower motor neurons (i[3]LMNs). CSFs were obtained from ALS patients homozygous for the risk UNC13A rs12608932 single nucleotide polymorphism (CC) and for the corresponding major allele (AA), ALS patients with C9ORF72 hexanucleotide repeat expansion, and individuals affected by normal pressure hydrocephalus as non-disease controls (ND). A chronic and low-dose sodium arsenite (ARS) treatment was used as positive control of oxidative stress. We found that 10 % ALS CSF treatment for 48 h was not sufficient to induce significant alterations in viability, autophagic flux, axonal degeneration, DNA damage, and Golgi apparatus integrity in healthy i[3]LMNs, in contrast to ARS treatment. Only UNC13A CC CSF significantly increased protein aggregation and Golgi apparatus fragments dimension. RNA-sequencing revealed that all ALS and ND CSFs induced expression changes of few genes, while chronic ARS deregulated the expression of thousands of genes, mostly involved in inflammation and synapse biology. In this work, we demonstrated that in our experimental settings only CSF from UNC13A CC patients induced some ALS-associated pathological features in healthy i[3]LMNs. Further studies will be required to elucidate the mechanistic link between the risk UNC13A genotype and CSF composition and toxicity.}, } @article {pmid40249897, year = {2025}, author = {Siegler, JE and Galetta, SL}, title = {Editors' Note: Physical Activity, Fitness, and Long-Term Risk of Amyotrophic Lateral Sclerosis: A Prospective Cohort Study.}, journal = {Neurology}, volume = {104}, number = {9}, pages = {e213609}, doi = {10.1212/WNL.0000000000213609}, pmid = {40249897}, issn = {1526-632X}, } @article {pmid40249896, year = {2025}, author = {Kawada, T}, title = {Reader Response: Physical Activity, Fitness, and Long-Term Risk of Amyotrophic Lateral Sclerosis: A Prospective Cohort Study.}, journal = {Neurology}, volume = {104}, number = {9}, pages = {e209943}, doi = {10.1212/WNL.0000000000209943}, pmid = {40249896}, issn = {1526-632X}, } @article {pmid40249895, year = {2025}, author = {Vaage, AM and Nakken, O}, title = {Author Response: Physical Activity, Fitness, and Long-Term Risk of Amyotrophic Lateral Sclerosis: A Prospective Cohort Study.}, journal = {Neurology}, volume = {104}, number = {9}, pages = {e209962}, doi = {10.1212/WNL.0000000000209962}, pmid = {40249895}, issn = {1526-632X}, } @article {pmid40248372, year = {2025}, author = {Dai, ZS and Zhang, M and Deng, YY and Zhou, N and Tian, Y}, title = {Efficacy of a novel artificial liver versatile plasma purification system in patients with acute-on-chronic liver failure.}, journal = {World journal of gastroenterology}, volume = {31}, number = {14}, pages = {103892}, pmid = {40248372}, issn = {2219-2840}, mesh = {Humans ; *Acute-On-Chronic Liver Failure/mortality/therapy/blood ; Female ; Male ; Middle Aged ; Prospective Studies ; *Liver, Artificial ; Treatment Outcome ; Aged ; Patient Readmission/statistics & numerical data ; Adult ; Length of Stay/statistics & numerical data ; Kaplan-Meier Estimate ; Follow-Up Studies ; Peritonitis/epidemiology/etiology ; China/epidemiology ; }, abstract = {BACKGROUND: We have innovatively amalgamated membrane blood purification and centrifugal blood cell separation technologies to address the limitations of current artificial liver support (ALS) models, and develop a versatile plasma purification system (VPPS) through centrifugal plasma separation.

AIM: To investigate the influence of VPPS on long-term rehospitalization and mortality rates among patients with acute-on-chronic liver failure (ACLF).

METHODS: This real-world, prospective study recruited inpatients diagnosed with ACLF from the Second Xiangya Hospital of Central South University between October 2021 and March 2024. Patients were categorized into the VPPS and non-VPPS groups based on the distinct ALS models administered to them. Self-administered questionnaires, clinical records, and self-reported data served as the primary methods for data collection. The laboratory results were evaluated at six distinct time points. All patients were subjected to follow-up assessments for > 12 months. Kaplan-Meier survival analyses and Cox proportional hazards models were used to evaluate the risks of hospitalization and mortality during the follow-up period.

RESULTS: A cohort of 502 patients diagnosed with ACLF was recruited, with 260 assigned to the VPPS group. On comparing baseline characteristics, the VPPS group exhibited a significantly shorter length of stay, higher incidence of spontaneous peritonitis and pulmonary aspergillosis compared to the non-VPPS group (P < 0.05). Age [hazard ratio (HR) = 1.142, 95%CI: 1.01-1.23, P = 0.018), peritonitis (HR = 2.825, 95%CI: 1.07-6.382, P = 0.026), albumin (HR = 0.67, 95%CI: 0.46-0.942, P = 0.023), total bilirubin (HR = 1.26, 95%CI: 1.01-3.25, P = 0.021), international normalized ratio (HR = 1.97, 95%CI: 1.21-2.908, P = 0.014), and VPPS/non-VPPS (HR = 3.24, 95%CI: 2.152-4.76, P < 0.001) were identified as significant independent predictors of mortality in both univariate and multivariate analyses throughout the follow-up period. Kaplan-Meier survival analyses demonstrated significantly higher rehospitalization and mortality rates in the non-VPPS group compared to the VPPS group during follow-up of ≥ 2 years (log-rank test, P < 0.001).

CONCLUSION: These findings suggest that VPPS is safe and has a positive influence on prognostic outcomes in patients with ACLF.}, } @article {pmid40247237, year = {2025}, author = {Pehlivanidis, A and Kouklari, EC and Kalantzi, E and Korobili, K and Tagkouli, E and Papanikolaou, K}, title = {Self-reported symptoms of attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and affective lability in discriminating adult ADHD, ASD and their co-occurrence.}, journal = {BMC psychiatry}, volume = {25}, number = {1}, pages = {391}, pmid = {40247237}, issn = {1471-244X}, mesh = {Humans ; *Attention Deficit Disorder with Hyperactivity/diagnosis/psychology/complications ; *Autism Spectrum Disorder/diagnosis/psychology/complications ; Male ; Adult ; Female ; Self Report ; Diagnosis, Differential ; Middle Aged ; Young Adult ; Psychiatric Status Rating Scales ; *Affective Symptoms/diagnosis/psychology ; Comorbidity ; Surveys and Questionnaires ; }, abstract = {BACKGROUND: To diagnose and manage adults with Attention Deficit Hyperactivity Disorder (ADHD), Autism Spectrum Disorder (ASD), or their co-occurrence (ADHD + ASD), clinicians must identify specific features that differentiate these diagnostic categories. Self-report questionnaires targeting specific features are widely used and, together with clinical assessments, provide reliable diagnoses. Although affective lability is present in various psychiatric disorders, it lacks specificity when screening for ADHD in the general population, and its discriminant value for ADHD, ASD, and ADHD + ASD has not been studied.

METHODS: This study involved 300 adults without intellectual developmental disorder (188 male) who received an ADHD (n = 174), ASD (n = 68), or ADHD + ASD (n = 58) diagnosis after a multidisciplinary consensus decision according to DSM-5 criteria. Before clinical assessment, all patients requesting evaluation for one of these diagnoses completed questionnaires on an online platform. The assessment instruments included a modified version of the Barkley Adult ADHD Rating Scale (BAARS IV) for ADHD, the Autism Spectrum Quotient (AQ) and the Empathy Quotient (EQ) for ASD features, and the Affective Lability Scale (ALS) for affective lability. Total scores and sub-scores of the instruments were compared among the three groups. Additionally, stepwise logistic regression analyses were conducted to identify specific measures that contribute to group discrimination.

RESULTS: Results revealed distinct patterns in symptomatology as expected. The ADHD and the ADHD + ASD groups presented significantly higher ALS total score compared to ASD. Stepwise logistic regression analyses identified specific measures contributing to group differentiation. ASD vs. ADHD + ASD discrimination included BAARS IV current total score and EQ total score. The subscale anger from ALS in addition with BAARS IV past total score and AQ total score were the factors that discriminated ADHD diagnosis from the co-occurrence of ADHD and ASD. Finally, BAARS IV past total score, BAARS IV current inattention, AQ total score, and EQ total score were found to differentiate ADHD from ASD.

CONCLUSIONS: The study highlights the significance of incorporating emotional dimensions in diagnostic frameworks and may contribute valuable insights for clinicians differentiating neurodevelopmental conditions.}, } @article {pmid40247229, year = {2025}, author = {Samudi Raju, C and Kono, M and Looi, KW and Ong, JX and Tan, CA and Ang, CS and Tan, PHY and Shamnugam, H and Sekaran, SDKC and Syed Omar, SF and Lum, LCS}, title = {Low atypical lymphocyte score as a predictor of non-severe dengue.}, journal = {BMC infectious diseases}, volume = {25}, number = {1}, pages = {551}, pmid = {40247229}, issn = {1471-2334}, mesh = {Humans ; *Dengue/diagnosis/blood/immunology/pathology ; Prospective Studies ; Male ; Female ; Adult ; Middle Aged ; *Lymphocytes/pathology ; Lymphocyte Count ; Severity of Illness Index ; Young Adult ; Prognosis ; Aged ; Adolescent ; }, abstract = {BACKGROUND: Severe dengue has been linked to the presence of atypical lymphocytes, which can be quantified using the Q-flag parameter on a hematology analyzer. A higher atypical lymphocyte count has previously been associated with severe dengue. We aimed to evaluate the feasibility of the atypical lymphocyte score to provide an early prognosis for dengue severity.

METHOD: A prospective observational study enrolled adult patients admitted to the Infectious Disease ward with a febrile illness of less than 7 days. Blood samples obtained daily until discharge, were processed with XN-20 hematology analyzer with specific attention given to atypical lymphocyte score. Severe dengue cases were classified according to the 2009 World Health Organization Classification.

RESULTS: A total of 287 cases of laboratory-confirmed dengue, including 25 severe cases, were included. Dengue fever compared to non-dengue patients manifested increased lymphocytes within the high fluorescent zone on Day 6, The atypical lymphocyte score (ALS) of severe dengue showed an early rise, reaching a saturation point of 300 and remaining stable within the timeframe of days 4 to 8 post-fever onset. All but one severe dengue patient had a score exceeding 100 on day 4 post fever onset.

CONCLUSION: An atypical lymphocyte score below 100 on day 4 post fever onset, may serve as a predictive indicator that severe dengue is less likely to develop, potentially allowing for a lower level of medical intervention. These findings may contribute to more efficient resource allocation during outbreaks.

TRIAL REGISTRATION: The study was registered under National Medical Research Registration of Malaysia, (NMRR-18-3347-45473, 1 Sept 2019).}, } @article {pmid40245393, year = {2025}, author = {Musson, LS and Mitic, N and Leigh-Valero, V and Onambele-Pearson, G and Knox, L and Steyn, FJ and Holdom, CJ and Dick, TJ and van Eijk, RP and van Unnik, JW and Botman, LC and Beswick, E and Murray, D and Griffiths, A and McDermott, C and Hobson, E and Chaouch, A and Hodson-Tole, E}, title = {The Use of Digital Devices to Monitor Physical Behavior in Motor Neuron Disease: Systematic Review.}, journal = {Journal of medical Internet research}, volume = {27}, number = {}, pages = {e68479}, pmid = {40245393}, issn = {1438-8871}, mesh = {Humans ; *Exercise ; *Motor Neuron Disease/diagnosis/physiopathology ; *Wearable Electronic Devices ; }, abstract = {BACKGROUND: Motor neuron disease (MND) is a progressive and incurable neurodegenerative disease. The Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) is the primary clinical tool for assessing disease severity and progression in MND. However, despite its widespread use, it does not adequately capture the extent of physical function decline. There is an urgent need for sensitive measures of disease progression that can be used to robustly evaluate new treatments. Measures of physical function derived from digital devices are beginning to be used to assess disease progression. There is value in establishing a consensus approach to standardizing the use of such devices.

OBJECTIVE: We aimed to explore how digital devices are being used to quantify free-living physical behavior in MND. We evaluated the feasibility and assessed the implications for monitoring physical behavior for future clinical trials and clinical practice.

METHODS: Systematic searches of 4 databases were performed in October 2023 and June 2024. Peer-reviewed English-language articles (including preprints) that examined how people living with MND used digital devices to assess their free-living physical behavior were included. Study reporting quality was assessed using a 22-item checklist (maximum possible score=44 points).

RESULTS: In total, 12 articles met the inclusion criteria for data extraction. All studies were longitudinal and observational in design, but data collection, analysis, and reporting protocols varied. Quality assessment scores ranged between 19 and 40 points. Sample sizes ranged between 10 and 376 people living with MND at baseline, declining over the course of the study. Most studies used an accelerometer device worn on the wrist, chest, hip, or ankle. Participants were typically asked to continuously wear devices for 1 to 8 days at 1- to 4-month intervals, with studies running for 12 weeks to 24 months. Some studies asked participants to wear the device continuously for the full duration. Studies derived traditional end points focusing on duration, intensity, and frequency of physical activity or nontraditional end points focusing on features of an individual's movement patterns. The correlation coefficients (r) between physical behavior end points and ALSFRS-R ranged from 0.31 to 0.78. Greater monitoring frequencies and improved end point sensitivity were shown to provide smaller sample size requirements and shorter durations for hypothetical clinical trials. People living with MND found using devices acceptable and reported a low burden. Adherence assessed in 8 (67%) studies was good, ranging from approximately 86% to 96%, with differences evident between wear locations. The perspectives of other end users and implications on clinical practice were not explored.

CONCLUSIONS: Remote monitoring of free-living physical behavior in MND is in its infancy but has the potential to quantify physical function. It is essential to develop a consensus statement, working toward agreed and standardized methods for data collection, analysis, and reporting.}, } @article {pmid40244212, year = {2025}, author = {Zhang, M and Zhou, H and Pan, Y and Wei, L}, title = {A pregnant woman with a 5-year history of amyotrophic lateral sclerosis: A case report.}, journal = {International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics}, volume = {}, number = {}, pages = {}, doi = {10.1002/ijgo.70173}, pmid = {40244212}, issn = {1879-3479}, support = {202414030736//Medical and Health Science and Technology Project of Shandong Province/ ; ZHKY202423//Chinese Nursing Association Scientific Research Project/ ; QDFY+X 2023125//the Clinical Medicine +X Project of the Affiliated Hospital of Qingdao University/ ; }, } @article {pmid40244186, year = {2025}, author = {Hu, C and Jiang, Y and Ma, C and Xu, F and Cui, C and Du, X and Chen, J and Zhu, L and Yu, S and He, X and Yu, W and Wang, Y and Xu, X}, title = {Decreased Cdk2 Activity Hindered Embryonic Development and Parthenogenesis Induction in Silkworm, Bombyx mori L.}, journal = {International journal of molecular sciences}, volume = {26}, number = {7}, pages = {}, pmid = {40244186}, issn = {1422-0067}, support = {2021C02072//Technological Grant of Zhejiang for Breeding New Agricultural Varieties/ ; 32100377//National Natural Science Foundation of China/ ; CARS-18//Key Scientific and the China Agriculture Research System of MOF and MARA/ ; }, mesh = {Animals ; *Bombyx/embryology/genetics/enzymology ; *Parthenogenesis/drug effects ; *Cyclin-Dependent Kinase 2/metabolism/antagonists & inhibitors/genetics ; *Embryonic Development/drug effects ; *Insect Proteins/metabolism/genetics/antagonists & inhibitors ; Female ; }, abstract = {Cyclin-dependent protein kinase 2 (Cdk2), an important member of the serine/threonine-specific protein kinase family, plays a critical regulatory role in biological processes. Previous studies have demonstrated that Cdk2 is involved in the arrest and resumption of meiosis in mammalian oocytes. In this study, we explored the function of Cdk2 through parthenogenetic lines (PLs) and corresponding amphigonic lines (ALs) in a model lepidopteran insect silkworm, Bombyx mori L. Our findings revealed a positive correlation between Cdk2 activity and the parthenogenesis induction rate. The pharmacological inhibition of Cdk2 using the specific inhibitor AUZ454 not only significantly reduced the parthenogenesis induction rate but also caused developmental delays in embryos. These results demonstrate that Cdk2 is essential for parthenogenesis success and is a potential target gene for biological reproductive regulation.}, } @article {pmid40244061, year = {2025}, author = {Tseriotis, VS and Liampas, A and Lazaridou, IZ and Karachrysafi, S and Vavougios, GD and Hadjigeorgiou, GM and Papamitsou, T and Kouvelas, D and Arnaoutoglou, M and Pourzitaki, C and Mavridis, T}, title = {Repulsive Guidance Molecule-A as a Therapeutic Target Across Neurological Disorders: An Update.}, journal = {International journal of molecular sciences}, volume = {26}, number = {7}, pages = {}, pmid = {40244061}, issn = {1422-0067}, mesh = {Humans ; Animals ; *Nervous System Diseases/metabolism/drug therapy ; *Nerve Tissue Proteins/metabolism/antagonists & inhibitors/genetics ; *GPI-Linked Proteins/metabolism/antagonists & inhibitors/genetics ; Molecular Targeted Therapy ; Neurodegenerative Diseases/metabolism/drug therapy ; }, abstract = {Repulsive guidance molecule-a (RGMa) has emerged as a significant therapeutic target in a variety of neurological disorders, including neurodegenerative diseases and acute conditions. This review comprehensively examines the multifaceted role of RGMa in central nervous system (CNS) pathologies such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis, neuromyelitis optica spectrum disorder, spinal cord injury, stroke, vascular dementia, auditory neuropathy, and epilepsy. The mechanisms through which RGMa contributes to neuroinflammation, neuronal degeneration, and impaired axonal regeneration are herein discussed. Evidence from preclinical studies associate RGMa overexpression with negative outcomes, such as increased neuroinflammation and synaptic loss, while RGMa inhibition, particularly the use of agents like elezanumab, has shown promise in enhancing neuronal survival and functional recovery. RGMa's responses concerning immunomodulation and neurogenesis highlight its potential as a therapeutic avenue. We emphasize RGMa's critical role in CNS pathology and its potential to pave the way for innovative treatment strategies in neurological disorders. While preclinical findings are encouraging so far, further clinical trials are needed to validate the safety and efficacy of RGMa-targeted therapies.}, } @article {pmid40243810, year = {2025}, author = {Flores, SV and Lillo, P and Levi-Monsalve, A and Roco-Videla, Á and Montaña, R}, title = {Genetic ancestry and risk allele C9orf72 rs3849942 T for amyotrophic lateral sclerosis in Latin American populations.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {26}, number = {3-4}, pages = {379-381}, doi = {10.1080/21678421.2024.2447459}, pmid = {40243810}, issn = {2167-9223}, mesh = {Female ; Humans ; Male ; Middle Aged ; Alleles ; *Amyotrophic Lateral Sclerosis/genetics/ethnology ; *C9orf72 Protein/genetics ; *Genetic Predisposition to Disease/genetics ; Latin America/epidemiology ; *Polymorphism, Single Nucleotide/genetics ; White People/genetics ; *South American People/genetics ; }, abstract = {This study examines the relationship between genetic ancestry and the rs3849942 T allele, linked to ALS, in 347 Latin American individuals from the 1000 Genomes Project. Ancestry proportions were estimated using 446 AIMs, and associations were analyzed via logistic regression. Higher Native American ancestry significantly reduced the likelihood of carrying the T allele, while European ancestry increased it. These findings emphasize the importance of incorporating genetic diversity into ALS research.}, } @article {pmid40243699, year = {2025}, author = {Xu, R and Kang, Q and Yang, X and Yi, P and Zhang, R}, title = {Unraveling Molecular Targets for Neurodegenerative Diseases Through Caenorhabditis elegans Models.}, journal = {International journal of molecular sciences}, volume = {26}, number = {7}, pages = {}, pmid = {40243699}, issn = {1422-0067}, support = {32270739//National Natural Science Foundation of China/ ; }, mesh = {*Caenorhabditis elegans/genetics/metabolism ; Animals ; *Neurodegenerative Diseases/metabolism/genetics/drug therapy/pathology ; *Disease Models, Animal ; Humans ; Caenorhabditis elegans Proteins/metabolism/genetics ; }, abstract = {Neurodegenerative diseases (NDDs), including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), and prion disease, represent a group of age-related disorders that pose a growing and formidable challenge to global health. Despite decades of extensive research that has uncovered key genetic factors and biochemical pathways, the precise molecular mechanisms underlying these diseases and effective therapeutic strategies remain elusive. Caenorhabditis elegans (C. elegans) has emerged as a powerful model organism for studying NDDs due to its unique biological features such as genetic tractability, conserved molecular pathways, and ease of high-throughput screening. This model provides an exceptional platform for identifying molecular targets associated with NDDs and developing novel therapeutic interventions. This review highlights the critical role of C. elegans in elucidating the complex molecular mechanisms of human NDDs, with a particular focus on recent advancements and its indispensable contributions to the discovery of molecular targets and therapeutic strategies for these NDDs.}, } @article {pmid40243477, year = {2025}, author = {Romano, R and Del Fiore, VS and Ruotolo, G and Mazzoni, M and Rosati, J and Conforti, FL and Bucci, C}, title = {Lysosomal Dysfunction in Amyotrophic Lateral Sclerosis: A Familial Case Linked to the p.G376D TARDBP Mutation.}, journal = {International journal of molecular sciences}, volume = {26}, number = {7}, pages = {}, pmid = {40243477}, issn = {1422-0067}, support = {PRIN2022 N. 2022XTM2S3//Ministero dell'università e della ricerca/ ; PRIN2022 PNRR N. P2022FBZXY//Ministero dell'università e della ricerca/ ; D.M. n. 737 of 25.06.2021//Ministero dell'università e della ricerca/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology ; *Lysosomes/metabolism/pathology ; *DNA-Binding Proteins/genetics/metabolism ; Motor Neurons/metabolism/pathology ; *Mutation ; Fibroblasts/metabolism/pathology ; Male ; Female ; Induced Pluripotent Stem Cells/metabolism ; Middle Aged ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease affecting motor neurons. Consequent to the loss of these cells, neuromuscular functions decline, causing progressive weakness, muscle wasting, and paralysis, leading to death in 2 to 5 years. More than 90% of ALS cases are sporadic, while the remaining 10% of cases are familial, due to mutations in 40 different genes. One of the most common genes to be mutated in ALS is TARDBP (transactive response DNA binding protein 43), which encodes TDP-43 (TAR DNA-binding protein 43). A mutation in exon 6 of TARDBP causes the aminoacidic substitution G376D in the C-terminal region of TDP-43, leading to its cytoplasmic mislocalization and aggregation. In fibroblasts derived from patients carrying this mutation, we found a strong increase in lysosome number, with overexpression and higher nuclear translocation of the transcription factor TFEB. In contrast, lysosomal functionality was deeply compromised. Interestingly, lysosomal activity was unaffected at an early stage of the disease, worsening in more advanced stages. Moreover, we observed the same pathological phenotype in iPSC (induced pluripotent stem cells)-derived patient motor neurons carrying the G376D mutation. Therefore, this mutation compromises the functionality of lysosomes, possibly contributing to neurodegeneration.}, } @article {pmid40243463, year = {2025}, author = {Fan, X and Diao, W and Wang, H and Yin, X and Qian, W}, title = {Interferon Regulatory Factors as a Potential Therapeutic Target for Neuroinflammation: A Focus on Alzheimer's Disease.}, journal = {International journal of molecular sciences}, volume = {26}, number = {7}, pages = {}, pmid = {40243463}, issn = {1422-0067}, support = {82473926//National Natural Science Foundation of China/ ; 81872875//National Natural Science Foundation of China/ ; 81170317//National Natural Science Foundation of China/ ; 81473218//National Natural Science Foundation of China/ ; 81503077//National Natural Science Foundation of China/ ; JC2023042//the project of Nantong Natural Science Foundation/ ; }, mesh = {Humans ; *Alzheimer Disease/metabolism/drug therapy/pathology ; Animals ; *Interferon Regulatory Factors/metabolism/genetics ; *Neuroinflammatory Diseases/metabolism/drug therapy ; Signal Transduction ; Inflammation/metabolism ; }, abstract = {Interferon Regulatory Factors (IRFs) are critical modulators of immune and inflammatory responses, yet their roles in Alzheimer's disease (AD) and other neurodegenerative disorders remain incompletely understood. While IRFs are recognized for their regulatory functions in neuroinflammation, microglial activation, and neuronal survival, their dual roles as both drivers of pathological inflammation and mediators of neuroprotective pathways underscore a sophisticated regulatory paradox in neurodegenerative disorders. This review aims to synthesize current evidence on IRF-mediated neuroinflammation in AD and related diseases, focusing on the multifaceted functions of key IRF family members, including IRF1, IRF3, and IRF7. We critically evaluate their divergent roles: IRF1 and IRF3, for instance, exacerbate neuroinflammatory cascades and amyloid-beta (Aβ) pathology in AD, whereas IRF7 may paradoxically suppress inflammation under specific conditions. Additionally, we explore IRF dysregulation in Parkinson's disease, multiple sclerosis, amyotrophic lateral sclerosis, and Huntington's disease, emphasizing shared and distinct mechanisms across neurodegenerative disorders. Restoring IRF balance through genetic manipulation, small-molecule inhibitors, or microbiome-derived modulators could attenuate neuroinflammation, enhance Aβ clearance, and protect neuronal integrity. Ultimately, this work provides a framework for future research to harness IRF signaling pathways in the development of precision therapies for AD and other neurodegenerative diseases.}, } @article {pmid40241787, year = {2025}, author = {Wölfel, SM and Widmann, CN and Castro-Gomez, S and Weydt, P and Tacik, P and Heneka, MT}, title = {Cognitive capacity in amyotrophic lateral sclerosis: the value of diagnostic markers in cerebrospinal fluid and the influence of nutrition and pulmonary function.}, journal = {Brain communications}, volume = {7}, number = {2}, pages = {fcaf137}, pmid = {40241787}, issn = {2632-1297}, abstract = {Amyotrophic lateral sclerosis is an incurable neurodegenerative disease that is fatal with a median of 3-4 years. It is characterized by degeneration of the first and second motor neurons. In addition to physical limitations, neuropsychological abnormalities occur in more than 50% of cases. This leads to a rapid loss of autonomy and increases the need for care. An individual prognosis for the course of the disease, in particular the development of cognitive and behavioural abnormalities, is not yet possible As part of our investigations, we focused on cognitive performance and behavioural abnormalities measured by the Edinburgh Cognitive and Behavioural ALS Screen in patients with amyotrophic lateral sclerosis and investigated possible prognostic biomarkers in cerebrospinal fluid as well as modifiable factors such as nutrition and lung function. A retrospective data analysis of 99 patients with amyotrophic lateral sclerosis cases examined between 2018 and 2021 at the Department for Neurodegenerative Diseases and Gerontopsychiatry at the University Hospital of Bonn, using Edinburgh Cognitive and Behavioural ALS Screen, revealed that elevated levels of total tau and phospho-tau 181 were associated with diminished performance of patients with amyotrophic lateral sclerosis on the Edinburgh Cognitive and Behavioural ALS Screen. Additionally, weight loss during the course of the disease has been observed to have a deleterious impact on cognitive performance. Moreover, we were able to demonstrate a previously insufficiently described correlation between abnormalities in the Edinburgh Cognitive and Behavioural ALS Screen and low-normal thiamine levels in serum. The hypothesis that reduced lung function has a negative effect on cognitive performance was not supported by our findings. The initial onset of amyotrophic lateral sclerosis, whether bulbar or spinal, does not appear to affect cognition and behaviour measured using Edinburgh Cognitive and Behavioural ALS Screen. Furthermore, our findings confirm the utility of the Edinburgh Cognitive and Behavioural ALS Screen in identifying a behavioural variant frontotemporal dementia in amyotrophic lateral sclerosis patients who have been previously diagnosed by experienced neurologists using the Rascovsky criteria. This development facilitates a more precise utilization of complex diagnostic instruments. Our results provide insight into the prognosis of patients with amyotrophic lateral sclerosis in terms of cognitive performance and behavioural abnormalities as the disease progresses, as well as potential therapeutic approaches to stabilize and support neuropsychological abnormalities. The importance of total tau as a widely available prognostic marker should be emphasized. Additionally, new avenues of research are emerging, particularly regarding the role of thiamine in amyotrophic lateral sclerosis.}, } @article {pmid40241786, year = {2025}, author = {Hernández-Gloria, JJ and Jaramillo-Gonzalez, A and Savić, AM and Mrachacz-Kersting, N}, title = {Toward brain-computer interface speller with movement-related cortical potentials as control signals.}, journal = {Frontiers in human neuroscience}, volume = {19}, number = {}, pages = {1539081}, pmid = {40241786}, issn = {1662-5161}, abstract = {Brain Computer Interface spellers offer a promising alternative for individuals with Amyotrophic Lateral Sclerosis (ALS) by facilitating communication without relying on muscle activity. This study assessed the feasibility of using movement related cortical potentials (MRCPs) as a control signal for a Brain-Computer Interface speller in an offline setting. Unlike motor imagery-based BCIs, this study focused on executed movements. Fifteen healthy subjects performed three spelling tasks that involved choosing specific letters displayed on a computer screen by performing a ballistic dorsiflexion of the dominant foot. Electroencephalographic signals were recorded from 10 sites centered around Cz. Three conditions were tested to evaluate MRCP performance under varying task demands: a control condition using repeated selections of the letter "O" to isolate movement-related brain activity; a phrase spelling condition with structured text ("HELLO IM FINE") to simulate a meaningful spelling task with moderate cognitive load; and a random condition using a randomized sequence of letters to introduce higher task complexity by removing linguistic or semantic context. The success rate, defined as the presence of an MRCP, was manually determined. It was approximately 69% for both the control and phrase conditions, with a slight decrease in the random condition, likely due to increased task complexity. Significant differences in MRCP features were observed between conditions with Laplacian filtering, whereas no significant differences were found in single-site Cz recordings. These results contribute to the development of MRCP-based BCI spellers by demonstrating their feasibility in a spelling task. However, further research is required to implement and validate real-time applications.}, } @article {pmid40240969, year = {2025}, author = {Xia, H and Wang, ZH and Wang, XB and Gao, MR and Jiang, S and Du, XY and Yang, XL}, title = {Investigating the genetic association of mitochondrial DNA copy number with neurodegenerative diseases.}, journal = {BMC neurology}, volume = {25}, number = {1}, pages = {160}, pmid = {40240969}, issn = {1471-2377}, support = {2023B03003//Autonomous Region Key Research and Development Project/ ; 2022TSYCLJ0066//the Tian-Shan Talent Program/ ; 82371258//the National Natural Science Foundation of China/ ; ZYYD2022C17//the Central Guiding Local Science and Technology Development Special Fund Project/ ; }, mesh = {Humans ; *DNA, Mitochondrial/genetics ; *Neurodegenerative Diseases/genetics ; *DNA Copy Number Variations/genetics ; Genome-Wide Association Study ; Mendelian Randomization Analysis ; *Genetic Predisposition to Disease/genetics ; Male ; Cohort Studies ; Female ; }, abstract = {OBJECTIVE: This study aims to investigate the causal relationship between Mitochondrial DNA (mtDNA) copy number and several common neurodegenerative diseases (NDs).

METHODS: We conducted a bidirectional two-sample Mendelian randomization (MR) analysis using data from genome-wide association studies (GWAS) as instrumental variables (IVs). After screening for relevance and potential confounders, we estimated the association between mtDNA copy number and NDs, including Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic lateral sclerosis (ALS), and Multiple sclerosis (MS). Additionally, we validated our findings using GWAS data on mtDNA copy number from Longchamps et al., sourced from the Genetics Epidemiology Consortium and the UK Biobank (UKB) aging study cohort.

RESULTS: A GWAS analysis of 395,718 UKB participants found no significant association between mtDNA copy number and the risk of NDs, including AD (OR = 0.956, P = 0.708), PD (OR = 1.223, P = 0.179), ALS (OR = 0.972, P = 0.374), and MS (OR = 0.932, P = 0.789). Similarly, reverse MR analysis revealed no significant relationship between genetic predictions of NDs and mtDNA copy number: AD (OR = 0.987, P = 0.062), PD (OR = 0.997, P = 0.514), ALS (OR = 0.974, P = 0.706), and MS (OR = 1.003, P = 0.181).

CONCLUSION: Although mitochondrial dysfunction is implicated in the pathogenesis of NDs, no clear evidence supports a causal role for mtDNA copy number. The relationship between mtDNA copy number and NDs is likely mediated by more complex molecular regulatory mechanisms. Further research is required to elucidate these intricate interactions.}, } @article {pmid40238886, year = {2025}, author = {Cheemala, A and Kimble, AL and Burrage, EN and Helming, SB and Tyburski, JD and Leclair, NK and Omar, OM and Zuberi, AR and Murphy, M and Jellison, ER and Reese, B and Hu, X and Lutz, CM and Yan, R and Murphy, PA}, title = {Amyotrophic lateral sclerosis and frontotemporal dementia mutation reduces endothelial TDP-43 and causes blood-brain barrier defects.}, journal = {Science advances}, volume = {11}, number = {16}, pages = {eads0505}, pmid = {40238886}, issn = {2375-2548}, support = {R00 HL125727/HL/NHLBI NIH HHS/United States ; K99 HL125727/HL/NHLBI NIH HHS/United States ; U54 OD020351/OD/NIH HHS/United States ; P30 CA034196/CA/NCI NIH HHS/United States ; RF1 NS074256/NS/NINDS NIH HHS/United States ; R01 NS074256/NS/NINDS NIH HHS/United States ; RF1 AG046929/AG/NIA NIH HHS/United States ; RF1 NS117449/NS/NINDS NIH HHS/United States ; R01 AG046929/AG/NIA NIH HHS/United States ; }, mesh = {*Blood-Brain Barrier/metabolism/pathology ; *DNA-Binding Proteins/genetics/metabolism ; Animals ; *Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology ; *Frontotemporal Dementia/genetics/metabolism/pathology ; Mice ; *Mutation ; Humans ; *Endothelial Cells/metabolism/pathology ; Disease Models, Animal ; Brain/metabolism/pathology ; }, abstract = {Mutations in the TARDBP gene encoding TDP-43 protein are linked to loss of function in neurons and familial frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). We recently identified reduced nuclear TDP-43 in capillary endothelial cells (ECs) of donors with ALS-FTD. Because blood-brain barrier (BBB) permeability increases in ALS-FTD, we postulated that reduced nuclear TDP-43 in ECs might contribute. Here, we show that nuclear TDP-43 is reduced in ECs of mice with an ALS-FTD-associated mutation in TDP-43 (Tardbp[G348C]) and that this leads to cell-autonomous loss of junctional complexes and BBB integrity. Targeted excision of TDP-43 in brain ECs recapitulates BBB defects and loss of junctional complexes and ultimately leads to fibrin deposition, gliosis, phospho-Tau accumulation, and impaired memory and social interaction. Transcriptional changes in TDP-43-deficient ECs resemble diseased brain ECs. These data show that nuclear loss of TDP-43 in brain ECs disrupts the BBB and causes hallmarks of FTD.}, } @article {pmid40237254, year = {2025}, author = {Russek, M and Peltner, J and Haenisch, B}, title = {Supplementing Single-Arm Trials with External Control Arms-Evaluation of German Real-World Data.}, journal = {Clinical pharmacology and therapeutics}, volume = {}, number = {}, pages = {}, doi = {10.1002/cpt.3684}, pmid = {40237254}, issn = {1532-6535}, abstract = {As single-arm trials (SATs) are increasingly used in pharmaceutical research, the validity of such study designs needs to be critically assessed. We characterize the feasibility of supplementing SATs with real-world data (RWD)-derived external control arms by determining the proportion of SATs on breast cancer and amyotrophic lateral sclerosis (ALS) for which an external control arm based on RWD can be constructed. The main outcome measure is the number and percentage of trials for which all important eligibility criteria and at least one primary endpoint could be identified in one of five German RWD sources. We surveyed all SATs concerning breast cancer or ALS treatment registered in the European Union's clinical trial registers between 2004 and 2023. Ten out of 379 breast cancer SATs and 2 of 11 ALS SATs could feasibly be supplemented with RWD-derived external control arms, if all important eligibility criteria and a primary endpoint have to be identifiable in the RWD source. Ninety-three breast cancer trials had at least one outcome ascertainable in a RWD source, and 35 trials had all important eligibility criteria recorded in a RWD source. Nine ALS trials had at least one primary endpoint ascertainable in RWD sources, and 2 had all important eligibility criteria recorded in a RWD source. Our study shows that SATs with RWD-derived external control arms will rarely be suitable to establish treatment effects of medicines in the current setting for the investigated phenotypes and that SATs should be designed with limitations of the source of external controls in mind.}, } @article {pmid40237114, year = {2025}, author = {Thompson, OL and Russell, JA and Stockman, SK and Swall, JL and Simmons, T}, title = {Assessing the effectiveness of alternate light sources in the search for skeletal remains.}, journal = {Journal of forensic sciences}, volume = {70}, number = {4}, pages = {1501-1508}, pmid = {40237114}, issn = {1556-4029}, mesh = {Humans ; Swine ; Animals ; Deer ; *Bone and Bones ; *Lighting/instrumentation ; Forensic Anthropology/methods ; *Body Remains ; Fluorescence ; Models, Animal ; *Light ; }, abstract = {Many search and recovery operations for human skeletal remains are unsuccessful due to difficulties recognizing bones in outdoor environments even when evidence indicates the last known whereabouts of missing individuals. Though the collagen component of bone is known to emit fluorescence, this property has not been leveraged consistently during skeletal remains searches. Thirty-six mock searches were completed in 5000 ft[2] zones of eastern deciduous forest by volunteers associated with the Virginia Department of Emergency Management. Pig and deer bones were scattered and partially concealed under brush and leaf cover. Pairs of volunteers were allowed up to 1 h to conduct searches in their usual pattern. Nighttime searches were conducted with handheld alternate light source (ALS) devices (uvBeast™, Crime-lite[®], ForenScope, and Labino AB), which produced ultraviolet (385-395 nm), violet (395-425 nm), blue (~455 nm), cyan (~510 nm), or green (~530 nm) lights. Filtered safety glasses were paired with appropriate ALS. Daytime searches were conducted under the same parameters, without ALS. Results indicated that (1) nighttime searches with ALS produced a recovery rate more than triple that of daytime searches (p < 0.0001) and that they were often completed more quickly, and (2) the violet Crime-lite[®], due to breadth of illumination and strength of fluorescent response, consistently produced the highest recovery rate (95%). Data suggest that nighttime searches with ALS can be used both as the primary search method for locating and recovering human skeletal remains, and as a secondary method for recovering any bones expected to be present but not found during daylight searches.}, } @article {pmid40236412, year = {2025}, author = {Jude, JJ and Levi-Aharoni, H and Acosta, AJ and Allcroft, SB and Nicolas, C and Lacayo, BE and Card, NS and Wairagkar, M and Brandman, DM and Stavisky, SD and Willett, FR and Williams, ZM and Simeral, JD and Hochberg, LR and Rubin, DB}, title = {An intuitive, bimanual, high-throughput QWERTY touch typing neuroprosthesis for people with tetraplegia.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, doi = {10.1101/2025.04.01.25324990}, pmid = {40236412}, support = {I01 RX003803/RX/RRD VA/United States ; I50 RX002864/RX/RRD VA/United States ; U01 NS123101/NS/NINDS NIH HHS/United States ; R01 DC014034/DC/NIDCD NIH HHS/United States ; I01 RX004820/RX/RRD VA/United States ; K23 DC021297/DC/NIDCD NIH HHS/United States ; U01 DC017844/DC/NIDCD NIH HHS/United States ; }, abstract = {Recognizing keyboard typing as a familiar, high information rate communication paradigm, we developed an intracortical brain computer interface (iBCI) typing neuroprosthesis providing bimanual QWERTY keyboard functionality for people with paralysis. Typing with this iBCI involves only attempted finger movements, which are decoded accurately with as few as 30 calibration sentences. Sentence decoding is improved using a 5-gram language model. This typing neuroprosthesis performed well for two iBCI clinical trial participants with tetraplegia - one with ALS and one with spinal cord injury. Typing speed is user-regulated, reaching 110 characters per minute, resulting in 22 words per minute with a word error rate of 1.6%. This resembles able-bodied typing accuracy and provides higher throughput than current state-of-the-art hand motor iBCI decoding. In summary, a typing neuroprosthesis decoding finger movements, provides an intuitive, familiar, and easy-to-learn paradigm for individuals with impaired communication due to paralysis.}, } @article {pmid40236149, year = {2025}, author = {Strell, P and Waldron, MA and Johnson, S and Shetty, A and Crane, AT and Steer, CJ and Low, WC}, title = {Characterization of the intraspecies chimeric mouse brain at embryonic day 12.5.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2025.03.31.646380}, pmid = {40236149}, issn = {2692-8205}, support = {R01 AI173804/AI/NIAID NIH HHS/United States ; }, abstract = {Incidence of neurodegenerative diseases such as Alzheimer's, Parkinson's, Huntington's, and amyotrophic lateral sclerosis have increased dramatically as life expectancy at birth has risen year-over-year and the population ages. Neurological changes within the central nervous system, specifically the brain, include cell loss and deterioration that impact motor function, memory, executive function, and mood. Available treatments are limited and often only address symptomatic manifestations of the disease rather than disease progression. Cell transplantation therapy has shown promise for treating neurodegenerative diseases, but a source of autologous cells is required. Blastocyst complementation provides an innovative method for generating those autologous neural cells. By injecting mouse induced pluripotent stem cells (iPSCs) into a wild type (WT) mouse blastocyst, we generated a chimeric mouse brain derived of both donor and host neuronal and non-neuronal cells. An embryonic day 12.5 (E12.5), automated image analysis of mouse-mouse chimeric brains showed the presence of GFP-labeled donor-derived dopaminergic and serotonergic neuronal precursors. GFP-labeled donor-derived cholinergic precursor neurons and non-neuronal microglia-like and macrophage-like cells were also observed using more conventional imaging analysis software. This work demonstrates that the generation of mouse-mouse chimeric neural cells is possible; and that characterization of early neuronal and non-neuronal precursors provides a first step towards utilizing these cells for cell transplantation therapies for neurodegenerative diseases.}, } @article {pmid40235960, year = {2025}, author = {Basgaran, A and Lymberopoulos, E and Burchill, E and Reis-Dehabadi, M and Sharma, N}, title = {Machine learning determines the incidence of Alzheimer's disease based on population gut microbiome profile.}, journal = {Brain communications}, volume = {7}, number = {2}, pages = {fcaf059}, pmid = {40235960}, issn = {2632-1297}, abstract = {The human microbiome is a complex and dynamic community of microbes, thought to have symbiotic benefit to its host. Influences of the gut microbiome on brain microglia have been identified as a potential mechanism contributing to neurodegenerative diseases, such as Alzheimer's disease, motor neurone disease and Parkinson's disease (Boddy SL, Giovannelli I, Sassani M, et al. The gut microbiome: A key player in the complexity of amyotrophic lateral sclerosis (ALS). BMC Med. 2021;19(1):13). We hypothesize that population level differences in the gut microbiome will predict the incidence of Alzheimer's disease using machine learning methods. Cross-sectional analyses were performed in R, using two large, open-access microbiome datasets (n = 959 and n = 2012). Countries in these datasets were grouped based on Alzheimer's disease incidence and the gut microbiome profiles compared. In countries with a high incidence of Alzheimer's disease, there is a significantly lower diversity of the gut microbiome (P < 0.05). A permutational analysis of variance test (P < 0.05) revealed significant differences in the microbiome profile between countries with high versus low incidence of Alzheimer's disease with several contributing taxa identified: at a species level Escherichia coli, and at a genus level Haemophilus and Akkermansia were found to be reproducibly protective in both datasets. Additionally, using machine learning, we were able to predict the incidence of Alzheimer's disease within a country based on the microbiome profile (mean area under the curve 0.889 and 0.927). We conclude that differences in the microbiome can predict the varying incidence of Alzheimer's disease between countries. Our results support a key role of the gut microbiome in neurodegeneration at a population level.}, } @article {pmid40235867, year = {2025}, author = {Sundararaju, U and Rajakumar, HK}, title = {Prognostic value of neutrophil-to-lymphocyte ratio in gastric cancer: Enhancing clinical relevance.}, journal = {World journal of gastrointestinal oncology}, volume = {17}, number = {4}, pages = {103128}, pmid = {40235867}, issn = {1948-5204}, abstract = {Gastric cancer (GC) is a leading cause of cancer-related deaths, highlighting the need for reliable prognostic biomarkers to guide treatment. Wei et al's systematic review and meta-analysis evaluates the neutrophil-to-lymphocyte ratio (NLR) as a potential biomarker for GC patients undergoing neoadjuvant chemotherapy. NLR is a simple and cost-effective measure of systemic inflammation that shows promise in predicting treatment response and survival outcomes, including overall survival and progression-free survival. However, variations in NLR thresholds and timing of measurements affect its accuracy and clinical utility. Moreover, the studies reviewed primarily involved Asian populations, which may limit the generalizability of the findings. To improve NLR's clinical relevance, future research should focus on standardizing NLR thresholds, refining measurement timing, and incorporating additional inflammatory markers like platelet-to-lymphocyte ratio and Glasgow prognostic score. Addressing confounders and including diverse patient populations will help improve NLR's reliability as a prognostic marker for GC.}, } @article {pmid40235786, year = {2025}, author = {Wang, LP and Yang, C and Fu, JY and Zhang, XY and Shen, XM and Shi, NL and Wu, HL and Gao, XR}, title = {A preliminary study of steady-state visually-evoked potential-based non-invasive brain-computer interface technology as a communication aid for patients with amyotrophic lateral sclerosis.}, journal = {Quantitative imaging in medicine and surgery}, volume = {15}, number = {4}, pages = {3469-3479}, pmid = {40235786}, issn = {2223-4292}, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that affects motor neurons, leading to severe disability and ultimately death. Communication difficulties are common in ALS patients as the disease progresses; thus, alternative communication aids need to be explored. This study sought to examine the use and effect of steady-state visually-evoked potential (SSVEP)-based non-invasive brain-computer interface (BCI) technology as a communication aid for patients with ALS and to examine possible influencing factors.

METHODS: In total, 12 patients with ALS were selected, and a 40-character target selection was performed using SSVEP-based non-invasive BCI technology. The patients were presented with specific visual stimuli, and nine-lead electroencephalogram (EEG) signals in the occipital region were acquired when the patients were looking at the target. Using the feature recognition analysis method, the final output was the characters recognized by the patients. The basic clinical data of the patients (e.g., age, gender, course of disease, affected area, and ALS functional scale score) were collected, and the BCI accuracy rate, information transmission rate, and average SSVEP recognition time were calculated.

RESULTS: The results revealed that the recognition efficiency of the ALS patients varied. The accuracy potential increased as the stimulus duration extended, highlighting the possibility for improvement via further optimization. The results also showed that the experimental design schedules typically used for healthy individuals may not be entirely suitable for ALS patients, which presents an exciting opportunity to tailor future studies to better meet the unique needs of ASL patients. Further, the results revealed the necessity of using customized experimental schedules in future studies, which could lead to more relevant and effective data collection for ALS patients.

CONCLUSIONS: The study found that SSVEP-based non-invasive BCI technology has promising potential as a communication aid for ALS patients. While further algorithm optimization and comprehensive studies with larger sample sizes are necessary, the initial findings are encouraging, and could lead to the development of more effective communication solutions that are specifically tailored to address the challenges faced by ALS patients.}, } @article {pmid40235752, year = {2025}, author = {Huang, NX and Zeng, JY and Huang, HW and Fang, SY and Chen, S and Li, JQ and Chen, HJ and Zou, ZY}, title = {Association of glymphatic system disturbance with neural dysfunction in amyotrophic lateral sclerosis.}, journal = {Quantitative imaging in medicine and surgery}, volume = {15}, number = {4}, pages = {3445-3457}, pmid = {40235752}, issn = {2223-4292}, abstract = {BACKGROUND: Formation and aggregation of pathological proteins in the brain constitutes a critical hallmark of amyotrophic lateral sclerosis (ALS). However, the role of the glymphatic system in the clearance of pathological proteins in ALS remains unclear. The purpose of this cross-sectional study was to evaluate glymphatic system disturbance in ALS and its relation to neural function.

METHODS: This study included 38 healthy controls (HCs) and 30 patients with ALS who underwent diffusion tensor imaging (DTI) and resting-state functional magnetic resonance imaging (rs-fMRI). The disease severity, duration, and progression rate of ALS were recorded. Glymphatic system function was indirectly evaluated by DTI analysis along the perivascular space (ALPS) surrounding the deep medullary vein. Neural activity was examined in sensorimotor-related brain areas by measuring amplitude of low-frequency fluctuation (ALFF) based on rs-fMRI. A two-sample t-test or Mann-Whitney test was used to examine between-group differences in ALPS, diffusivities measured along the x-, y-, and z-axis in the association (Dxx_association, Dyy_association, Dzz_association) and projection (Dxx_projection, Dyy_projection, Dzz_projection) fiber areas, and ALFF indices. The associations between ALPS, diffusivities, ALFF, and clinical assessments were determined via Spearman correlation analysis, and diagnostic performance was evaluated with receiver operating characteristic curve analysis.

RESULTS: Patients with ALS exhibited significantly decreased ALPS and increased diffusivities (Dyy_association and Dyy_projection) as compared to HCs (all P values <0.05). Patients with ALS showed decreased ALFF in sensorimotor-related regions, including the bilateral primary motor and somatosensory areas (all P values <0.001) and left supplementary motor area (P=0.031). ALPS and diffusivities were correlated with ALFF in the sensorimotor-motor regions (all P values <0.05), and ALPS and ALFF correlated with disease severity and duration (all P values <0.05). ALPS, diffusivities, and ALFF showed moderate ability to diagnose ALS.

CONCLUSIONS: The glymphatic system function was impaired in ALS. This may contribute to spontaneous neural activity disturbance and could represent a mechanism for the development of sensorimotor deficits frequently observed in patients with ALS.}, } @article {pmid40235273, year = {2025}, author = {Scelsa, SN and MacGowan, DJL}, title = {Disease Modification in SOD1-ALS With Tofersen May Result in Serious CNS Inflammation.}, journal = {Muscle & nerve}, volume = {71}, number = {6}, pages = {928-931}, doi = {10.1002/mus.28413}, pmid = {40235273}, issn = {1097-4598}, } @article {pmid40234983, year = {2025}, author = {Xie, Q and Li, K and Chen, Y and Li, Y and Jiang, W and Cao, W and Yu, H and Fan, D and Deng, B}, title = {Gene therapy breakthroughs in ALS: a beacon of hope for 20% of ALS patients.}, journal = {Translational neurodegeneration}, volume = {14}, number = {1}, pages = {19}, pmid = {40234983}, issn = {2047-9158}, support = {81901273//National Natural Science Foundation of China/ ; ZCLY24H0903//Natural Science Foundation of Zhejiang Province/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/therapy/genetics ; Humans ; *Genetic Therapy/methods/trends ; Animals ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disease that remains incurable. Although the etiologies of ALS are diverse and the precise pathogenic mechanisms are not fully understood, approximately 20% of ALS cases are caused by genetic factors. Therefore, advancing targeted gene therapies holds significant promise, at least for the 20% of ALS patients with genetic etiologies. In this review, we summarize the main strategies and techniques of current ALS gene therapies based on ALS risk genes, and review recent findings from animal studies and clinical trials. Additionally, we highlight ALS-related genes with well-understood pathogenic mechanisms and the potential of numerous emerging gene-targeted therapeutic approaches for ALS.}, } @article {pmid40234916, year = {2025}, author = {Park, KH and Yu, E and Choi, S and Kim, S and Park, C and Lee, JE and Kim, KW}, title = {Optogenetic induction of TDP-43 aggregation impairs neuronal integrity and behavior in Caenorhabditis elegans.}, journal = {Translational neurodegeneration}, volume = {14}, number = {1}, pages = {20}, pmid = {40234916}, issn = {2047-9158}, support = {P40 OD010440/OD/NIH HHS/United States ; NRF-2022R1A2C1003766//Ministry of Education, Science and Technology/ ; RS-2024-00331685//Ministry of Food and Drug Safety/ ; }, mesh = {Animals ; Caenorhabditis elegans ; *Optogenetics/methods ; *DNA-Binding Proteins/metabolism/genetics ; *TDP-43 Proteinopathies/metabolism/pathology/genetics ; *Neurons/metabolism/pathology ; *Protein Aggregation, Pathological/metabolism/pathology ; Disease Models, Animal ; Animals, Genetically Modified ; Protein Aggregates/physiology ; Caenorhabditis elegans Proteins/metabolism ; *Behavior, Animal/physiology ; }, abstract = {BACKGROUND: Cytoplasmic aggregation of TAR DNA binding protein 43 (TDP-43) in neurons is one of the hallmarks of TDP-43 proteinopathy. Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) are closely associated with TDP-43 proteinopathy; however, it remains uncertain whether TDP-43 aggregation initiates the pathology or is a consequence of it.

METHODS: To demonstrate the pathology of TDP-43 aggregation, we applied the optoDroplet technique in Caenorhabditis elegans (C. elegans), which allows spatiotemporal modulation of TDP-43 phase separation and assembly.

RESULTS: We demonstrate that optogenetically induced TDP-43 aggregates exhibited insolubility similar to that observed in TDP-43 proteinopathy. These aggregates increased the severity of neurodegeneration, particularly in GABAergic motor neurons, and exacerbated sensorimotor dysfunction in C. elegans.

CONCLUSIONS: We present an optogenetic C. elegans model of TDP-43 proteinopathy that provides insight into the neuropathological mechanisms of TDP-43 aggregates. Our model serves as a promising tool for identifying therapeutic targets for TDP-43 proteinopathy.}, } @article {pmid40234116, year = {2025}, author = {McHale-Owen, H and Faller, KME and Chaytow, H and Gillingwater, TH}, title = {Phosphoglycerate kinase 1 as a therapeutic target in neurological disease.}, journal = {Trends in molecular medicine}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.molmed.2025.03.008}, pmid = {40234116}, issn = {1471-499X}, abstract = {Phosphoglycerate kinase 1 (PGK1) is a highly conserved enzyme that catalyzes the initial ATP-producing step in glycolysis. Improving cellular energy production by increasing PGK1 activity may be beneficial in multiple neurological conditions where cell metabolism is dysregulated, including Parkinson's disease (PD) and motor neuron disease (MND). This review examines recent evidence that suggests increasing PGK1 activity may be beneficial in multiple neurological conditions and discusses the current challenges surrounding the development of PGK1-focused therapies. PGK1 has considerable therapeutic potential, but novel PGK1 activators are needed to maximize the benefit for patients.}, } @article {pmid40232694, year = {2024}, author = {Ichikawa, Y and Sato, B and Hirano, SI and Takefuji, Y and Satoh, F}, title = {Hydrogen inhalation therapy may ameliorate amyotrophic lateral sclerosis.}, journal = {Medical gas research}, volume = {14}, number = {3}, pages = {149-150}, pmid = {40232694}, issn = {2045-9912}, } @article {pmid40232582, year = {2025}, author = {Mehrnoosh, F and Rezaei, D and Pakmehr, SA and Nataj, PG and Sattar, M and Shadi, M and Ali-Khiavi, P and Zare, F and Hjazi, A and Al-Aouadi, RFA and Sapayev, V and Zargari, F and Alkhathami, AG and Ahmadzadeh, R and Khedmatgozar, M and Hamzehzadeh, S}, title = {The role of Panax ginseng in neurodegenerative disorders: mechanisms, benefits, and future directions.}, journal = {Metabolic brain disease}, volume = {40}, number = {4}, pages = {183}, pmid = {40232582}, issn = {1573-7365}, mesh = {Humans ; *Panax ; *Neurodegenerative Diseases/drug therapy/metabolism ; Animals ; *Ginsenosides/therapeutic use/pharmacology ; *Neuroprotective Agents/therapeutic use/pharmacology ; *Plant Extracts/therapeutic use/pharmacology ; Oxidative Stress/drug effects ; }, abstract = {Neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic lateral sclerosis (ALS), Multiple sclerosis (MS), and Huntington's disease (HD) represent a growing global health challenge, especially with aging populations. Characterized by progressive neuronal loss, these diseases lead to cognitive, motor, and behavioral impairments, significantly impacting patients' quality of life. Current therapies largely address symptoms without halting disease progression, underscoring the need for innovative, disease-modifying treatments. Ginseng, a traditional herbal medicine with well-known adaptogenic and neuroprotective properties, has gained attention as a potential therapeutic agent for neurodegeneration. Rich in bioactive compounds called ginsenosides, ginseng exhibits antioxidant, anti-inflammatory, and anti-apoptotic effects, making it a promising candidate for addressing the complex pathology of neurodegenerative diseases. Recent studies demonstrate that ginsenosides modulate disease-related processes such as oxidative stress, protein aggregation, mitochondrial dysfunction, and inflammation. In AD models, ginsenosides have been shown to reduce amyloid-beta accumulation and tau hyperphosphorylation, while in PD, they help protect dopaminergic neurons and mitigate motor symptoms. Ginseng's effects in ALS, MS, and HD models include improving motor function, extending neuronal survival, and reducing cellular toxicity. This review provides a comprehensive overview of the neuroprotective mechanisms of ginseng, emphasizing its therapeutic potential across various neurodegenerative diseases and discussing future research directions for its integration into clinical practice.}, } @article {pmid40232308, year = {2025}, author = {Wu, J and Xu, Y and Yin, T and Zhang, N and Fan, D and Ye, S}, title = {Unveiling structural damage of the corpus callosum in amyotrophic lateral sclerosis through diffusion tensor imaging and spread direction perspectives.}, journal = {Annals of medicine}, volume = {57}, number = {1}, pages = {2490822}, pmid = {40232308}, issn = {1365-2060}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/pathology/diagnostic imaging/physiopathology ; *Corpus Callosum/pathology/diagnostic imaging ; *Diffusion Tensor Imaging/methods ; Male ; Female ; Middle Aged ; Aged ; Adult ; Motor Cortex/pathology/diagnostic imaging ; }, abstract = {OBJECTIVE: Damage to the corpus callosum (CC) in amyotrophic lateral sclerosis (ALS) patients has been confirmed via electrophysiological, neuroimaging, and autopsy studies. Additionally, the CC is hypothesized to serve as a pathway for the spread of pathological information. This study aimed to investigate whether the CC plays a mediating role in the symptomatic spread of ALS.

METHODS: In this observational study, diffusion tensor imaging (DTI) data were acquired from 45 individuals with the upper motor neuron-dominant (UMN-D) phenotype of ALS. The UMN-D ALS patients were categorized into two groups based on the direction of symptom spread, including 25 patients with horizontal spread (group H) and 20 patients with vertical spread (group V). Diffusivity indices were derived through whole-brain analysis and probabilistic fiber tracking.

RESULTS: According to the voxel-based analysis and tract-based spatial statistics, differences in axial diffusivity (AD) in the CC were observed between disease subgroups, with patients in group H showing higher AD values than those in group V. Fiber tracking analysis revealed persistent differences in the AD indices of CC-primary motor cortex (PMC) fibers between the two disease subgroups.

CONCLUSION: In UMN-D ALS patients, the direction of symptom spread may be related to the degree of CC involvement. The AD metric may be a more specific indicator of CC damage.}, } @article {pmid40231507, year = {2025}, author = {Tecalco-Cruz, AC and Ramírez-Jarquín, JO and Medina Abreu, KH and Palacios-Serrato, EG and López-Cánovas, L and Zepeda-Cervantes, J and Oropeza-Martínez, E}, title = {Molecular Interplay of ISG15/ISGylation in Neuropathologies.}, journal = {CNS & neurological disorders drug targets}, volume = {}, number = {}, pages = {}, doi = {10.2174/0118715273378149250322050004}, pmid = {40231507}, issn = {1996-3181}, abstract = {ISG15 is a 15 kDa ubiquitin-like protein that covalently associates with its target proteins by a sequential enzymatic process known as ISGylation. Research on protein ISGylation has increased in recent years, and some studies have suggested that ISG15 is involved in neuroprotection and neurodegeneration mechanisms. This review outlines the current state of research on the implications of ISG15/ISGylation in other neuropathies such as malignant tumors, ataxia telangiectasia, ischemia, depression, and neurodegenerative diseases such as Alzheimer´s, Parkinson's diseases, multiple sclerosis, and amyotrophic lateral sclerosis. Based on the studies reported to date, ISG15/ ISGylation promotes the progression of brain tumors such as glioblastoma. Moreover, ISG15/ ISGylation seems to play a dual role in neuropathies, demonstrating a neuroprotective effect when there is acute brain damage, but ISG15/ISGylation is associated with reduced neuroprotection when there is chronic damage, such as in neurodegenerative diseases.}, } @article {pmid40231293, year = {2025}, author = {Smyth, BR and Patwardhan, S and Turner, EL and McLintock, S}, title = {Using Functional Resonance Analysis Method (FRAM) Modelling to Assess the Factors That Slow or Prevent Clinicians in Performing Advanced Life Support (ALS) During Crash Calls to Park House Mental Health Hospital.}, journal = {Cureus}, volume = {17}, number = {4}, pages = {e82231}, pmid = {40231293}, issn = {2168-8184}, abstract = {This Quality Improvement Project (QIP) aimed to improve the response system for crash calls at Park House Mental Health Hospital, supported by the North Manchester General Hospital Crash Team. Using a functional resonance analysis method (FRAM), the team identified inefficiencies in the Advanced Life Support (ALS) process, with delayed responses increasing patient mortality risks. Interviews with staff helped create "work-as-imagined" (WAI) and "work-as-done" (WAD) models, highlighting the underperformed functions like ward entry protocols, and fully stocked crash trolleys. Recommendations, including access cards, stock changes, and live simulations, were implemented, in an aim to improve ALS provision.}, } @article {pmid40230758, year = {2025}, author = {Bossei, AA and Al Zahrani, HA and Bossei, FA and Saadi, SM and Alsaedi, AS and Al Sulami, AQ and Al Asmari, EH and Aalam, AA and Khojah, IM}, title = {Emergency Physicians' Perceptions, Knowledge, and Attitudes Toward Family Presence During Resuscitation in the Emergency Department: A Multicenter Survey-Based Cross-Sectional Study.}, journal = {Cureus}, volume = {17}, number = {3}, pages = {e80612}, pmid = {40230758}, issn = {2168-8184}, abstract = {BACKGROUND: Cardiac arrest remains a significant public health issue, with high incidence rates in both in-hospital and out-of-hospital settings. The practice of family presence during resuscitation (FPDR) has gained attention for its potential benefits to patients and their families. This study evaluates the perceptions, knowledge, and attitudes of emergency physicians (EPs) regarding FPDR in the emergency department (ED) and aims to inform policy development at King Abdulaziz University Hospital in Jeddah, Saudi Arabia.

METHODS:  A multicenter cross-sectional study was conducted from January to April 2023, surveying EPs from multiple EDs across the western region of Saudi Arabia. Participants, certified in basic (BLS) or advanced life support (ALS), completed an anonymous online survey adapted from previous studies.

RESULTS: Our study surveyed 122 EPs, with 112 completing the survey. Of the participants, 49.1% were aged 25-29 years, 61.6% were men, and 58.9% had 1-4 years of work experience. Awareness of FPDR was reported by 67.9% (n = 76) of participants. Only 3.6% (n = 4) had a policy allowing FPDR, while 6.3% (n = 7) had a policy prohibiting it. Additionally, 49.1% (n = 55) supported implementing an FPDR policy. Awareness of FPDR was significantly higher among younger, male, and more experienced physicians (p < 0.05). Higher perception and practice scores were observed among those aware of FPDR, those who had participated in CPR with a family member, and those without a prohibiting policy (p < 0.05).

CONCLUSION: EPs in the western region of Saudi Arabia generally support FPDR, recognizing its potential benefits. However, concerns about its impact on performance and medicolegal issues warrant further exploration. To implement effective FPDR policies, these concerns must be addressed, along with efforts to promote awareness and training. Future research should expand to include broader healthcare settings and multidisciplinary teams to develop comprehensive, evidence-based guidelines.}, } @article {pmid40229738, year = {2025}, author = {Abdoalsadig, E and Hamid, M and Peck, A and Johar, L and Kimonis, V}, title = {Utilization of CoRDS registry to monitor quality of life in patients with VCP multisystem proteinopathy.}, journal = {Orphanet journal of rare diseases}, volume = {20}, number = {1}, pages = {178}, pmid = {40229738}, issn = {1750-1172}, mesh = {Humans ; Registries ; *Quality of Life ; Female ; Male ; *Valosin Containing Protein/genetics/metabolism ; Middle Aged ; Aged ; Myositis, Inclusion Body/genetics ; Adult ; Amyotrophic Lateral Sclerosis/genetics ; Osteitis Deformans/genetics ; Frontotemporal Dementia/genetics ; }, abstract = {BACKGROUND: VCP disease, also known as multisystem proteinopathy, is a rare, autosomal dominant, adult-onset, neuromuscular disease that is caused by variants in the valosin-containing protein (VCP) gene. VCP disease may exhibit one or more of the following primary features: inclusion body myopathy, Paget's disease of bone (PDB), Frontotemporal dementia, and amyotrophic lateral sclerosis. Due to its progressive nature, death normally occurs in their sixties due to respiratory and cardiac failure. The purpose of this study is to utilize the Cure VCP Disease patient registry hosted by the Coordination of Rare Diseases at Sanford (CoRDS) to conduct a prospective natural history study.

METHODS: Seventy-nine participants enrolled in the patient registry and answered demographic, VCP variant type, Patient-reported outcome measures (PROMs), and quality of life (QOL) questionnaires over the course of 3 years. We additionally investigated if any sex differences existed and if genotype-phenotype correlations affected the rate of progression of the varying clinical manifestations.

RESULTS: Overall, participants' mobility declined significantly as the disease progressed. Participants reported a 0.6% decline in upper extremity function, 1.2% decline in lower extremity function, and 0.3% decline in cognitive function per year of age. Furthermore, participants reported a 1.6% decline in upper and lower extremity function and a 0.1% decline in cognitive function per year of disease duration. The highest PROMs correlations were noted between overall health and lower extremity function, upper extremity function, fatigue, and the ability to perform vigorous activities. Genotype-phenotype correlations revealed no significant differences except for the absence of PDB in the p.Arg159Cys group.

CONCLUSION: The VCP CoRDS Registry was found to be a valuable tool for monitoring the QOL in patients with VCP disease and capturing patient perspectives for future clinical trials.}, } @article {pmid40229540, year = {2025}, author = {Ghimire, S and Kreilaus, F and Rosa Porto, R and Anderson, LL and Yerbury, JJ and Arnold, JC and Karl, T}, title = {Behavioural effects of oral cannabidiol (CBD) treatment in the superoxide dismutase 1 G93 A (SOD1[G93 A]) mouse model of amyotrophic lateral sclerosis.}, journal = {Psychopharmacology}, volume = {}, number = {}, pages = {}, pmid = {40229540}, issn = {1432-2072}, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease affecting voluntary muscle movement as well as cognitive and other behavioural domains at later disease stages. No effective treatment for ALS is currently available. Elevated neuroinflammation, oxidative stress and alterations to the endocannabinoid system are evident in ALS. The phytocannabinoid cannabidiol (CBD) has anti-inflammatory and anti-oxidant properties. Thus, we evaluated the remedial effects of chronic oral cannabidiol (CBD) treatment on ALS-relevant behavioural domains in the copper-zinc superoxide dismutase 1 (SOD1) mouse model of ALS that carries a G93A mutation (SOD1[G93A]).

METHODS: Male and female SOD1[G93A] and wild type-like (WT) littermates were fed either a control (CHOW) or CBD-enriched chow diet (equivalent to a dose of 36 mg/kg per day) beginning from 10 weeks of age. Bodyweight and motor performance were recorded weekly from 11 to 19 weeks and open field behaviours at 12 and 18 weeks. Mice were also tested for prepulse inhibition (PPI), social behaviours, as well as fear-associated memory.

RESULTS: CBD treatment ameliorated the bodyweight loss in female SOD1[G93A] mice, tended to reinstate sociability in SOD1[G93A] males, strengthened social recognition memory in SOD1[G93A] females, and improved the PPI response in younger SOD1[G93A] females at higher prepulse intensities. CBD had no effect on motor impairments but instead reversed the anxiolytic-like phenotype of 12-week-old male SOD1[G93A] mice and decreased the acoustic startle response and strengthened cue freezing in male mice.

CONCLUSION: Thus, the current remedial oral dose of CBD delayed disease progression (inferred by bodyweight) in both male and female mice and improve specific cognitive deficits of SOD1[G93A] mice in a sex specific manner without altering the motor phenotype.}, } @article {pmid40229296, year = {2025}, author = {Kumar, P and Bishnoi, R and Priyadarshini, P and Chhuneja, P and Singla, D}, title = {Understanding the structural basis of ALS mutations associated with resistance to sulfonylurea in wheat.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {12855}, pmid = {40229296}, issn = {2045-2322}, mesh = {*Acetolactate Synthase/genetics/chemistry/metabolism ; *Triticum/genetics/enzymology/drug effects ; *Sulfonylurea Compounds/pharmacology/chemistry ; *Herbicide Resistance/genetics ; Molecular Docking Simulation ; Herbicides/pharmacology ; *Plant Proteins/genetics/chemistry/metabolism ; Molecular Dynamics Simulation ; *Mutation ; Pyridines/pharmacology/chemistry ; }, abstract = {Developing herbicide-tolerant wheat varieties is highly desirable for effective weed management and improved crop yield. The enzyme acetolactate synthase (ALS) is the target enzyme for the sulfonylurea class of herbicides. The structural analysis of mutable sites in ALS is crucial for the generation of herbicide-resistant crops. Previous studies indicated that mutant lines of Triticum aestivum ALS (TaALS) with amino acid substitutions at P174, G631, and G632 residues provided resistance to sulfonylurea herbicide, nicosulfuron. The present study aimed to provide structural insights into mutable residues causing sulfonylurea herbicide resistance to TaALS enzyme through in-silico molecular docking and simulation approaches. The molecular docking analysis suggested a single point mutation at TaALS-P174S, its double mutant conformations (TaALS-G632S/P174S and TaALS-G631D/G632S) and associated triple mutant conformation (TaALS-G631D/G632S/P174S) to have the lowest binding affinity with nicosulfuron than the wild-type conformation of TaALS. Furthermore, the molecular dynamic simulation study confirms the weakest and more stable binding of the triple mutant conformation with nicosulfuron. Our computational study identifies a triple mutant conformation (TaALS-G631D/G632S/P174S) to be more effective in developing sulfonylurea herbicide-resistant wheat crops.}, } @article {pmid40228660, year = {2025}, author = {Veenstra, J and Ozog, D and Stephens, A}, title = {Response to Barbieri, "Response to Veenstra et al's 'Benzoyl peroxide acne treatment shows no significant association with benzene-related cancers: A multicenter retrospective analysis'".}, journal = {Journal of the American Academy of Dermatology}, volume = {93}, number = {2}, pages = {e71-e72}, doi = {10.1016/j.jaad.2025.03.090}, pmid = {40228660}, issn = {1097-6787}, } @article {pmid40226510, year = {2025}, author = {Ufarry Alvarado, AJ and Zaidi Pons, MA and Plaza Hernández, J and Torres Ortiz, C}, title = {Improvements of Paraquat Treatment in Liquid Media for Behavior and Neurodegenerative Tests.}, journal = {microPublication biology}, volume = {2025}, number = {}, pages = {}, pmid = {40226510}, issn = {2578-9430}, abstract = {Amyotrophic Lateral Sclerosis (ALS) is a disease characterized by misfolded and aggregated proteins that have toxic effects on motor neurons. The missense mutation, G85R, of the sod-1 gene associated with ALS displays locomotor impairments in Caenorhadbitis elegans (C. elegans). We treated the sod-1 (G85R) strain with 0 and 2.5 mM Paraquat treatments in a liquid M9 buffer for 4 hours and in solid NGM media for 18 hours. In both methodologies, the locomotion defects and neurodegeneration were significantly increased with 2.5 mM Paraquat. Our work provides evidence of methodology that is more cost effective, rapid and reproducible to perform behavior and neurodegenerative assay in worms.}, } @article {pmid40222103, year = {2025}, author = {Lum, JS and Brown, ML and Farrawell, NE and Bartlett, R and Chisholm, CG and Gorman, J and Dosseto, A and Dux, F and McInnes, LE and Ecroyd, H and McAlary, L and Crouch, PJ and Donnelly, PS and Yerbury, JJ}, title = {A polytherapy approach demonstrates therapeutic efficacy for the treatment of SOD1 associated amyotrophic lateral sclerosis.}, journal = {EBioMedicine}, volume = {115}, number = {}, pages = {105692}, pmid = {40222103}, issn = {2352-3964}, mesh = {*Amyotrophic Lateral Sclerosis/drug therapy/genetics/pathology/metabolism ; *Superoxide Dismutase-1/genetics/metabolism/chemistry ; Humans ; Organoselenium Compounds/pharmacology/administration & dosage/therapeutic use ; Isoindoles ; Animals ; Mice ; Azoles/pharmacology/administration & dosage ; Cell Line ; Drug Therapy, Combination ; Mutation ; Disease Models, Animal ; Cell Survival/drug effects ; Protein Folding ; Motor Neurons/metabolism/drug effects ; }, abstract = {BACKGROUND: SOD1 mutations are a significant contributor of familial amyotrophic lateral sclerosis (ALS) cases. SOD1 mutations increase the propensity for the protein to misfold and aggregate into insoluble proteinaceous deposits within motor neurons and neighbouring cells. The small molecule, CuATSM, has repeatedly shown in mouse models to be a promising therapeutic treatment for SOD1-associated ALS and is currently in Phase II/III clinical trials for the treatment of ALS. We have previously shown CuATSM stabilises various ALS-associated variants of the SOD1 protein, reducing misfolding and toxicity. Two additional FDA-approved small molecules, ebselen and telbivudine, have also been identified to reduce mutant SOD1 toxicity, providing additional potential therapeutic candidates that could be used in combination with CuATSM. Here, we aimed to investigate if CuATSM, ebselen and telbivudine (CET) polytherapy could improve on the therapeutic efficacy of CuATSM monotherapy for the treatment of SOD1-associated ALS.

METHODS: We utilised a 3D checkerboard approach to investigate whether a matrix of different concentrations CuATSM, ebselen and telbivudine could provide therapeutic improvements on cell survival, SOD1 folding and aggregation in SOD1[G93A]-transfected NSC-34 cells, compared to CuATSM alone. To progress the preclinical development of CET polytherapy, we evaluated the bioavailability and safety of in vivo polytherapy administration. Furthermore, we assessed and compared the effects of CET- and CuATSM-treatment on disease onset, motor function, survival and neuropathological features in SOD1[G93A] mice.

FINDINGS: CET polytherapy reduced inclusion formation and increased cell survival of NSC-34 cells overexpressing SOD1[G93A] compared to higher concentrations of CuATSM monotherapy. In addition, CET administration was bioavailable and tolerable in mice. CET treatment in SOD1[G93A] mice delayed disease onset, reduced motor impairments, and increased survival compared to vehicle- and CuATSM-treated mice. In line with these findings, biochemical analysis of lumbar spinal cords showed CET administration improved SOD1 folding, decreased misfolded SOD1 accumulation, and reduced motor neuron loss.

INTERPRETATION: These findings support CET polytherapy as an advantageous alternative compared to CuATSM monotherapy and highlight the potential of utilising small molecules targeting SOD1 as a polytherapy avenue for the treatment of SOD1-associated ALS.

FUNDING: This work was supported by a FightMND Drug Development Grant, an Australian National Health and Medical Research Council (NHMRC) Investigator Grant (No. 1194872) and a Motor Neuron Disease Research Institute of Australia Bill Gole Postdoctoral Fellowship.}, } @article {pmid40222004, year = {2025}, author = {Oliveri, F and Bicaj, M and Cillerai, M and Cabona, C and Gemelli, C and Uccelli, A and Schenone, A and Ferraro, PM}, title = {Prevalence of cognitive impairment in motor neuron diseases: alternative norming methods lead to considerably diverse estimates.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {26}, number = {5-6}, pages = {535-540}, doi = {10.1080/21678421.2025.2488294}, pmid = {40222004}, issn = {2167-9223}, mesh = {Humans ; Male ; Female ; Middle Aged ; *Cognitive Dysfunction/epidemiology/diagnosis/etiology ; Aged ; Prevalence ; *Motor Neuron Disease/epidemiology/complications/psychology ; Neuropsychological Tests ; Italy/epidemiology ; Amyotrophic Lateral Sclerosis/epidemiology ; Adult ; Aged, 80 and over ; }, abstract = {Objectives: Cognitive impairment (CI) is frequently observed in motor neuron diseases (MNDs), and the Edinburgh Cognitive and Behavioral ALS Screen (ECAS) represents the most widely used measure to evaluate it. For the Italian ECAS, two norming approaches are currently available: the "regression-based" (R) and the "2 standard deviation-based" (2SD). In this study, we therefore aimed at comparing those two methods for the detection of CI in MNDs. Methods: Raw ECAS scores from 160 MND patients were corrected using both the R and the 2SD methods. According to Strong's criteria, patients were then categorized as either cognitively normal (CN), with CI (ALSci), with behavioral impairment (ALSbi), or both (ALScbi). Results: Using the R approach, the frequency of below-cutoff performances was 3.12% for the ECAS total, 4.37% for the ALS specific, and 3.75% for the ALS nonspecific score. Using the 2SD method, the prevalence increased to 25.62% for the ECAS total, 21.25% for the ALS specific, and 23.12% for the ALS nonspecific score. The same increase was observed across all single tasks except for the digit span backward. The R-based frequency of Strong's diagnoses was 7.50% for ALSci, 15.62% for ALSbi, and 3.14% for ALScbi, which became 24.38% for ALSci, 8.75% for ALSbi and 10% for ALScbi with the 2SD method. Conclusions: The norming approach has a significant impact on the estimated prevalence of CI in MNDs, with the R method representing the most conservative one. These findings highlight the need for harmonized protocols in future studies evaluating CI in MNDs.}, } @article {pmid40220918, year = {2025}, author = {Key, J and Almaguer-Mederos, LE and Kandi, AR and Sen, NE and Gispert, S and Köpf, G and Meierhofer, D and Auburger, G}, title = {ATXN2L primarily interacts with NUFIP2, the absence of ATXN2L results in NUFIP2 depletion, and the ATXN2-polyQ expansion triggers NUFIP2 accumulation.}, journal = {Neurobiology of disease}, volume = {209}, number = {}, pages = {106903}, doi = {10.1016/j.nbd.2025.106903}, pmid = {40220918}, issn = {1095-953X}, mesh = {Animals ; Mice ; *Ataxin-2/metabolism/genetics ; Humans ; *RNA-Binding Proteins/metabolism ; Fibroblasts/metabolism ; Spinocerebellar Ataxias/metabolism/genetics ; *Nerve Tissue Proteins/metabolism/genetics ; Peptides/metabolism/genetics ; Mice, Knockout ; }, abstract = {The cytoplasmic Ataxin-2 (ATXN2) protein associates with TDP-43 in stress granules (SG) where RNA quality control occurs. Mutations in this pathway underlie Spinocerebellar Ataxia type 2 (SCA2) and Amyotrophic Lateral Sclerosis. In contrast, Ataxin-2-like (ATXN2L) is predominantly perinuclear, more abundant, and essential for embryonic life. Its sequestration into ATXN2 aggregates may contribute to disease. In this study, we utilized two approaches to clarify the roles of ATXN2L. First, we identified interactors through co-immunoprecipitation in both wild-type and ATXN2L-null murine embryonic fibroblasts. Second, we assessed the proteome profile effects using mass spectrometry in these cells. Additionally, we examined the accumulation of ATXN2L interactors in the SCA2 mouse model, Atxn2-CAG100-KnockIn (KIN). We observed that RNA-binding proteins, including PABPN1, NUFIP2, MCRIP2, RBMS1, LARP1, PTBP1, FMR1, RPS20, FUBP3, MBNL2, ZMAT3, SFPQ, CSDE1, HNRNPK, and HNRNPDL, exhibit a stronger association with ATXN2L compared to established interactors like ATXN2, PABPC1, LSM12, and G3BP2. Additionally, ATXN2L interacted with components of the actin complex, such as SYNE2, LMOD1, ACTA2, FYB, and GOLGA3. We noted that oxidative stress increased HNRNPK but decreased SYNE2 association, which likely reflects the relocalization of SG. Proteome profiling revealed that NUFIP2 and SYNE2 are depleted in ATXN2L-null fibroblasts. Furthermore, NUFIP2 homodimers and SYNE1 accumulate during the ATXN2 aggregation process in KIN 14-month-old spinal cord tissues. The functions of ATXN2L and its interactors are therefore critical in RNA granule trafficking and surveillance, particularly for the maintenance of differentiated neurons.}, } @article {pmid40220686, year = {2025}, author = {Coloma, L and Aramendia, J and Amigo, JM and Población, I and Alberquilla, F and Gorla, G and Huidobro, J and Torre-Fdez, I and Arana, G and Madariaga, JM}, title = {Analysis and interpretation of organic compounds in Martian meteorites with Raman imaging and chemometrics.}, journal = {Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy}, volume = {338}, number = {}, pages = {126194}, doi = {10.1016/j.saa.2025.126194}, pmid = {40220686}, issn = {1873-3557}, abstract = {One of the focuses of the research being developed on Mars (and consequently in samples from Mars) is the detection and study of organic compounds. Perseverance rover, currently analysing the Martian surface, is equipped with top-level instrumentation to detect mostly organic molecules. One of the techniques being used is Raman spectroscopy, due to its capability to analyse both inorganic and organic compounds simultaneously and its non-destructive and non-invasive properties. Unfortunately, it becomes cumbersome to determine the belonging of specific Raman bands in complex mixtures composed of an undetermined number of organic and inorganic molecules. Therefore, the study of this mixed information must be carried out with dedicated Chemometrics methods in order to understand the number of compounds present in a mixture (using Principal Component Analysis - PCA) and to obtain the pure spectra and the relative intensity of each compound (using spectral unmixing methods like Multivariate Curve Resolution - MCR). This manuscript presents an analysis of specific areas from the NWA 6148 Martian Nakhlite using Raman imaging, coupled with principal component analysis (PCA) and multivariate curve resolution (MCR), to determine the spatial distribution and spectral signatures of all organic and inorganic molecules present in these areas. The proposed methodology could be applied to the laboratory study of the future Mars-returned samples and other extraterrestrial samples returned to Earth.}, } @article {pmid40219902, year = {2025}, author = {Lapp, HS and Günther, R}, title = {SOD1-ALS mimicking an inflammatory neuropathy: a case report.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {26}, number = {5-6}, pages = {591-594}, doi = {10.1080/21678421.2025.2488296}, pmid = {40219902}, issn = {2167-9223}, mesh = {Humans ; Adult ; *Amyotrophic Lateral Sclerosis/genetics/diagnosis ; Diagnosis, Differential ; Male ; *Superoxide Dismutase-1/genetics ; Disease Progression ; }, abstract = {We present the case of a 36-year-old patient with a rapidly progressing SOD1-ALS, who was initially diagnosed as inflammatory acute motor axonal neuropathy due to contrast-enhancement of the lumbar spinal cord and a pure secondary motor neuron phenotype. Since the initiation of tofersen, disease progression and neurofilament levels impressively declined.}, } @article {pmid40218232, year = {2025}, author = {Iglesias, M and Cascón, JA and Maimó, A and Albaladejo, A and Andreo, F and Fernández, AS and Palazón, MM and González-Posada, IM and García, RG and Cordovilla, R}, title = {Evaluation of Diaphragmatic Ultrasound in Respiratory Functional Assessment in Patients with ALS.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {15}, number = {7}, pages = {}, pmid = {40218232}, issn = {2075-4418}, support = {becaPII2019//SOCIEDAD ESPAÑOLA DE NEUMOLOGÍA Y CIRUGÍA TORÁCICA (SEPAR)/ ; }, abstract = {Background: Diaphragmatic ultrasound emerges as a valuable non-invasive method for assessing diaphragm functionality in patients with amyotrophic lateral sclerosis (ALS). This study aimed to evaluate diaphragmatic ultrasound parameters in ALS, compare them with respiratory function tests, and determine whether they are associated with the need for non-invasive ventilation (NIV). Methods: This was a prospective, descriptive, and multicenter study across five centers, enrolling patients with recent diagnoses of ALS. At three-monthly visits, participants underwent both diaphragmatic ultrasound and pulmonary function testing. The following variables were analyzed: withdrawal from this study due to NIV or death, excursion, velocity, thickness, thickening fraction, and spirometric and respiratory muscle function values. Results: A total of 41 patients were included. A total of 24 (61.5%) patients left this study before the final year: 17 due to initiation of NIV, 4 due to clinical deterioration without NIV, and 3 due to death. Statistically significant moderate correlations were observed between diaphragmatic excursion and velocity and FVC and supine FVC (p < 0.001) and with MIP and the SNIP test (p < 0.05). No correlation was observed with thickening fraction. Additionally, lower baseline values in excursion were significantly associated with study withdrawal, along with reduced lung function (FVC, supine FVC, and MEP (p < 0.001). Conclusions: assessing diaphragmatic excursion by ultrasonography may serve as a useful tool for monitoring patients with ALS.}, } @article {pmid40217081, year = {2025}, author = {Baek, SH and Tae, WS and Auer, D and Kim, BJ}, title = {Brain diffusion tensor imaging changes linked to the split hand phenomenon in amyotrophic lateral sclerosis.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {12450}, pmid = {40217081}, issn = {2045-2322}, mesh = {*Diffusion Tensor Imaging ; *Amyotrophic Lateral Sclerosis/diagnosis/physiopathology ; *White Matter/diagnostic imaging/physiopathology ; Prospective Studies ; Nerve Conduction Studies ; Humans ; Male ; Female ; Aged ; Middle Aged ; Aged, 80 and over ; }, abstract = {The split-hand phenomenon is an early and specific feature of amyotrophic lateral sclerosis (ALS). This study aimed to investigate whether the split-hand phenomenon in ALS is associated with the white matter degeneration of the brain. Patients diagnosed with clinically definite or probable ALS were prospectively recruited and underwent both nerve conduction studies to assess the split-hand index (SHI) and brain diffusion tensor imaging (DTI). Demographic, clinical, and electrophysiological data were all collected. A total of 35 patients with ALS (18 male; median age, 66.0 years) were enrolled in this study. The axial diffusivity (AD) and mode of anisotropy (MO) values of DTI in the corticospinal tract (CST) positively correlated with the SHI. However, there were no significant correlations between the SHI and the fraction anisotropy (FA), mean diffusivity (MD), and radial diffusivity (RD) scalars. In addition, patients having ALS with bilateral split-hand phenomenon showed reduced AD values in the left CST and reduced MO values in the bilateral CST compared with those without the split-hand phenomenon. However, there were no significant differences in FA, MD, and RD scalars. Our findings suggest that the split-hand phenomenon is associated with degenerative brain changes, particularly in the CST.}, } @article {pmid40216746, year = {2025}, author = {Rezaei, A and Kocsis-Jutka, V and Gunes, ZI and Zeng, Q and Kislinger, G and Bauernschmitt, F and Isilgan, HB and Parisi, LR and Kaya, T and Franzenburg, S and Koppenbrink, J and Knogler, J and Arzberger, T and Farny, D and Nuscher, B and Katona, E and Dhingra, A and Yang, C and Gouna, G and LaClair, KD and Janjic, A and Enard, W and Zhou, Q and Hagan, N and Ofengeim, D and Beltrán, E and Gokce, O and Simons, M and Liebscher, S and Edbauer, D}, title = {Correction of dysregulated lipid metabolism normalizes gene expression in oligodendrocytes and prolongs lifespan in female poly-GA C9orf72 mice.}, journal = {Nature communications}, volume = {16}, number = {1}, pages = {3442}, pmid = {40216746}, issn = {2041-1723}, support = {390857198//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; 407495230//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; 423957469//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; 390857198//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; 390857198//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; 101057649//EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020)/ ; 101117710//EC | EU Framework Programme for Research and Innovation H2020 | H2020 European Institute of Innovation and Technology (H2020 The European Institute of Innovation and Technology)/ ; }, mesh = {Animals ; Female ; Mice ; *Oligodendroglia/metabolism/drug effects ; *Lipid Metabolism/drug effects/genetics ; *Amyotrophic Lateral Sclerosis/genetics/metabolism/drug therapy/pathology ; *C9orf72 Protein/genetics/metabolism ; Disease Models, Animal ; Male ; Cholesterol/metabolism ; Humans ; *2-Hydroxypropyl-beta-cyclodextrin/pharmacology ; Mice, Transgenic ; Myelin Sheath/metabolism ; Spinal Cord/metabolism/pathology ; Longevity/drug effects/genetics ; }, abstract = {Clinical and genetic research links altered cholesterol metabolism with ALS development and progression, yet pinpointing specific pathomechanisms remain challenging. We investigated how cholesterol dysmetabolism interacts with protein aggregation, demyelination, and neuronal loss in ALS. Bulk RNAseq transcriptomics showed decreased cholesterol biosynthesis and increased cholesterol export in ALS mouse models (GA-Nes, GA-Camk2a GA-CFP, rNLS8) and patient samples (spinal cord), suggesting an adaptive response to cholesterol overload. Consequently, we assessed the efficacy of the cholesterol-binding drug 2-hydroxypropyl-β-cyclodextrin (CD) in a fast-progressing C9orf72 ALS mouse model with extensive poly-GA expression and myelination deficits. CD treatment normalized cholesteryl ester levels, lowered neurofilament light chain levels, and prolonged lifespan in female but not male GA-Nes mice, without impacting poly-GA aggregates. Single nucleus transcriptomics indicated that CD primarily affected oligodendrocytes, significantly restored myelin gene expression, increased density of myelinated axons, inhibited the disease-associated oligodendrocyte response, and downregulated the lipid-associated genes Plin4 and ApoD. These results suggest that reducing excess free cholesterol in the CNS could be a viable ALS treatment strategy.}, } @article {pmid40216201, year = {2025}, author = {Cagalinec, M and Mohd, A and Borecka, S and Bultynck, G and Choubey, V and Yanovsky-Dagan, S and Ezer, S and Gasperikova, D and Harel, T and Jurkovicova, D and Kaasik, A and Liévens, JC and Maurice, T and Peviani, M and Richard, EM and Skoda, J and Skopkova, M and Tarot, P and Van Gorp, R and Zvejniece, L and Delprat, B}, title = {Improving mitochondria-associated endoplasmic reticulum membranes integrity as converging therapeutic strategy for rare neurodegenerative diseases and cancer.}, journal = {Biochimica et biophysica acta. Molecular cell research}, volume = {1872}, number = {5}, pages = {119954}, doi = {10.1016/j.bbamcr.2025.119954}, pmid = {40216201}, issn = {1879-2596}, mesh = {Humans ; *Neurodegenerative Diseases/metabolism/pathology/therapy/genetics ; *Endoplasmic Reticulum/metabolism/pathology ; *Mitochondria/metabolism/pathology ; *Neoplasms/metabolism/pathology/therapy/genetics ; Animals ; Receptors, sigma/metabolism ; Calcium Signaling ; Sigma-1 Receptor ; *Intracellular Membranes/metabolism ; Unfolded Protein Response ; Mitochondrial Membranes/metabolism ; }, abstract = {Membrane contact sites harbor a distinct set of proteins with varying biological functions, thereby emerging as hubs for localized signaling nanodomains underlying adequate cell function. Here, we will focus on mitochondria-associated endoplasmic reticulum membranes (MAMs), which serve as hotspots for Ca[2+] signaling, redox regulation, lipid exchange, mitochondrial quality and unfolded protein response pathway. A network of MAM-resident proteins contributes to the structural integrity and adequate function of MAMs. Beyond endoplasmic reticulum (ER)-mitochondrial tethering proteins, MAMs contain several multi-protein complexes that mediate the transfer of or are influenced by Ca[2+], reactive oxygen species and lipids. Particularly, IP3 receptors, intracellular Ca[2+]-release channels, and Sigma-1 receptors (S1Rs), ligand-operated chaperones, serve as important platforms that recruit different accessory proteins and intersect with these local signaling processes. Furthermore, many of these proteins are directly implicated in pathophysiological conditions, where their dysregulation or mutation is not only causing diseases such as cancer and neurodegeneration, but also rare genetic diseases, for example familial Parkinson's disease (PINK1, Parkin, DJ-1), familial Amyotrophic lateral sclerosis (TDP43), Wolfram syndrome1/2 (WFS1 and CISD2), Harel-Yoon syndrome (ATAD3A). In this review, we will discuss the current state-of-the-art regarding the molecular components, protein platforms and signaling networks underlying MAM integrity and function in cell function and how their dysregulation impacts MAMs, thereby driving pathogenesis and/or impacting disease burden. We will highlight how these insights can generate novel, potentially therapeutically relevant, strategies to tackle disease outcomes by improving the integrity of MAMs and the signaling processes occurring at these membrane contact sites.}, } @article {pmid40215589, year = {2025}, author = {Yaguchi, H and Miyagawa, S and Nakada, R and Yamamoto, S and Sakuta, K}, title = {Speech-swallow dissociation in velopharyngeal closure for differentiating amyotrophic lateral sclerosis and myasthenia gravis.}, journal = {Auris, nasus, larynx}, volume = {52}, number = {3}, pages = {239-242}, doi = {10.1016/j.anl.2025.03.003}, pmid = {40215589}, issn = {1879-1476}, mesh = {Humans ; Male ; Female ; Middle Aged ; Retrospective Studies ; Laryngoscopy ; *Myasthenia Gravis/diagnosis/physiopathology/complications ; *Amyotrophic Lateral Sclerosis/physiopathology/diagnosis/complications ; *Velopharyngeal Insufficiency/physiopathology/diagnosis/etiology ; Aged ; Diagnosis, Differential ; Adult ; *Deglutition Disorders/physiopathology/etiology ; Phonation ; Logistic Models ; *Speech ; }, abstract = {OBJECTIVE: Speech-swallow dissociation (SSD) in velopharyngeal closure on laryngoscopy is a sign of pseudobulbar palsy. We hypothesized that this finding could differentiate amyotrophic lateral sclerosis (ALS) from myasthenia gravis (MG). This study aimed to identify laryngoscopic findings useful in differentiating these two diseases.

METHODS: ALS and MG patients with bulbar symptoms who underwent fiberoptic laryngoscopy in our hospital were retrospectively examined. The following laryngoscopic items were evaluated: velopharyngeal incompetence (VPI) in phonation and swallowing, pharyngeal constriction, vocal cord movement, and salivary status.

RESULTS: One hundred seven patients (70 with ALS and 37 with MG) were included for analysis. The prevalence of VPI in phonation was significantly higher in the ALS group (40 % vs. 19 %; P = 0.027). The prevalence of SSD in velopharyngeal closure was also significantly higher in the ALS group (33 % vs. 3 %; P < 0.001). The other laryngoscopic findings did not differ between the groups. Multivariate logistic regression showed that SSD in velopharyngeal closure was independently associated with ALS (odds ratio, 26.64; 95 % confidence interval, 2.24-317.58; P = 0.009).

CONCLUSION: SSD in velopharyngeal closure is useful for differentiating ALS from MG.}, } @article {pmid40214652, year = {2025}, author = {Yu, G and Liu, X and Huang, W and Wang, S and Zhan, J and Ma, L and Li, H and Lin, X and Liu, T and Amine, K and Li, H}, title = {Ferromagnetic Atomic d-p Orbital Hybridization for Promoting Al-S Batteries.}, journal = {Advanced materials (Deerfield Beach, Fla.)}, volume = {37}, number = {24}, pages = {e2418784}, doi = {10.1002/adma.202418784}, pmid = {40214652}, issn = {1521-4095}, support = {tsqn202211118//Taishan Scholar Program of Shandong Province/ ; ZR2023YQ008//Excellent Youth Science Fund Project of Shandong China/ ; 2021KJ020//Outstanding Youth Innovation Team of Universities in Shandong Province/ ; 51804173//National Natural Science Foundation (NSFC) of China/ ; DE-SC0012704//Brookhaven National Laboratory under contract/ ; }, abstract = {Rechargeable aluminum-sulfur batteries (Al-S) are emerging as a promising alternative energy storage system beyond lithium-ion batteries due to their high energy density, abundant material resources, and economic efficiency. However, their practical application remains challenged by sluggish conversion kinetics, polysulfide shuttling, and low sulfur cathode utilization. While extensive studies have focused on enhancing polysulfide adsorption through catalytic strategies, the roles of electronic structure in dictating catalytic performance remain underexplored. Here, this work unveils the critical effect of unpaired electronic structure on the catalytic performance of single atom ferromagnetic transition metals through a systematic evaluation of three typical atomically dispersed ferromagnetic single atoms-Fe, Co, and Ni-supported on porous carbon (denoted as PC-SAFAs). Comprehensive characterizations and density functional theory (DFT) calculations reveal that the PC-SAFe catalysts, exhibiting the highest spin polarization arising from unpaired electrons, demonstrate the strongest interactions with polysulfide, thereby facilitating rapid and reversible polysulfide conversion reactions. Consequently, Al-S batteries incorporating the optimized PC-SAFe cathode achieve an impressive specific capacity of 508.8 mAh g[-1] at 1.0 A g[-1] after 500 cycles, along with much improved rate capability. This work provides a deeper understanding of the role of electronic structure in catalytic chemistry, and offers new insights for developing high-performance Al-S batteries.}, } @article {pmid40214138, year = {2025}, author = {Reus, LM and Willemse, SW and de Boer, SCM and De Houwer, J and Hartog, WL and Mol, MO and van Rooij, JGJ and Tesi, N and Donker Kaat, L and Hulsman, M and Vijverberg, EGB and Holstege, H and van Rheenen, W and Veldink, JH and van den Berg, LH and van Swieten, JC and Seelaar, H and van der Lee, SJ and van Es, MA and Pijnenburg, YAL}, title = {UNC13A Polymorphism Influences Survival in Patients with Frontotemporal Dementia.}, journal = {Annals of neurology}, volume = {97}, number = {6}, pages = {1062-1066}, pmid = {40214138}, issn = {1531-8249}, mesh = {Humans ; *Frontotemporal Dementia/genetics/mortality ; Male ; Female ; Middle Aged ; Aged ; *Nerve Tissue Proteins/genetics ; *Polymorphism, Single Nucleotide/genetics ; Genotype ; }, abstract = {UNC13A (rs12608932-CC) is associated with both amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), and shortens survival in ALS. We aim to describe the association for UNC13A and survival in FTD. We included 626 patients with FTD from Dutch memory clinics, including a subcohort of 150 patients with TDP-43 pathology. Survival analyses were performed using Cox proportional hazard models in a recessive manner. Homozygosity for rs12608932-C in UNC13A was associated with a shorter survival compared with other genotypes (hazard ratio [HR] = 1.28, 95% confidence interval [CI] = 1.02-1.60, p = 0.033), which has implications for patient counselling and trial design. ANN NEUROL 2025;97:1062-1066.}, } @article {pmid40213728, year = {2025}, author = {Grigore, A and Goebel, LJ}, title = {Frontotemporal Dementia and Amyotrophic Lateral Sclerosis: A Case Report and Clinical Insights.}, journal = {Cureus}, volume = {17}, number = {3}, pages = {e80329}, pmid = {40213728}, issn = {2168-8184}, abstract = {Primary care providers are often the first contact for patients with neurodegenerative illnesses, however, they may not be aware of the relationship of certain diseases that may have an impact on their patients' longevity. This case report reminds clinicians of the association between frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). Physicians should be aware of the association, because FTD commonly occurs first and may prepare clinicians to be alert to the signs of ALS in these patients, leading to earlier detection of ALS and the prescription of disease-modifying medication that may extend the lifespan of people with these diseases. We describe the case of a 61-year-old female patient initially presenting with cognitive decline most likely due to FTD who subsequently developed ALS.}, } @article {pmid40213632, year = {2025}, author = {Dezawa, M}, title = {Macrophage- and pluripotent-like reparative Muse cells are unique endogenous stem cells distinct from other somatic stem cells.}, journal = {Frontiers in bioengineering and biotechnology}, volume = {13}, number = {}, pages = {1553382}, pmid = {40213632}, issn = {2296-4185}, abstract = {Muse cells are endogenous reparative stem cells with dual characteristics: pluripotent-like and macrophage-like. They can be identified by the pluripotent surface marker stage-specific embryonic antigen-3-positive (SSEA-3 (+)) cells in the bone marrow, peripheral blood, and various organs, including the umbilical cord and amnion. Muse cells can differentiate into ectodermal, endodermal, and mesodermal lineage cells, self-renew, and selectively migrate to damaged sites by sensing one of the universal tissue damage signals, sphingosine-1-phosphate (S1P). At these sites, they phagocytose damaged/apoptotic cells and differentiate into the same cell type as the phagocytosed cells. In this manner, Muse cells replace damaged/apoptotic cells with healthy, functioning cells, thereby repairing tissues. Due to their specific immunosuppressive and immunotolerant mechanism, clinical trials have been conducted for acute myocardial infarction (AMI), subacute ischemic stroke, epidermolysis bullosa, amyotrophic lateral sclerosis (ALS), cervical spinal cord injury, neonatal hypoxic-ischemic encephalopathy (HIE), and COVID-19 acute respiratory distress syndrome. These trials involved the intravenous injection of ∼1.5 × 10[7] donor Muse cells without human leukocyte antigen (HLA) matching or immunosuppressant treatment, and they demonstrated safety and therapeutic efficacy. Thus, donor Muse cell treatment does not require gene manipulation, differentiation induction, or surgical intervention. These unique characteristics distinguish Muse cells from other somatic stem cells, such as mesenchymal stem cells, VSEL stem cells, and marrow-isolated adult multi-lineage inducible (MIAMI) cells.}, } @article {pmid40212206, year = {2025}, author = {Basnet, P and Singh, PR and Pudasaini, KR and Shrestha, S and Kc, A}, title = {A rare case of symmetric quadriplegia in a patient with Japanese encephalitis: a case report.}, journal = {Annals of medicine and surgery (2012)}, volume = {87}, number = {4}, pages = {2430-2433}, pmid = {40212206}, issn = {2049-0801}, abstract = {INTRODUCTION AND IMPORTANCE: Acute flaccid paralysis is a rare neurological complication of Japanese encephalitis (JE) infection, which may involve one or multiple limbs. Symmetric involvement of upper and lower limbs such as in this case is rarely reported.

PRESENTATION OF CASE: We present a case of a 30-year-old male from Terai region of Nepal who presented with fever, altered level of consciousness, and symmetrical quadriplegia. Based on these clinical findings, cerebrospinal fluid (CSF) analysis was done which came back negative. And based on results, polymerase chain reaction for herpes simplex virus types I and II was done which came out negative. Other neurological conditions such as amyotrophic lateral sclerosis and spinal dystrophy were ruled out because of the presence of fever and altered mental status. He was eventually diagnosed with JE based on his CSF analysis and positive result for JE serology/IgM Antibody Capture Enzyme-Linked Immunosorbent Assay test.

CLINICAL DISCUSSION: The patient presented with fever, altered mental status, and symmetrical flaccid paralysis of the bilateral upper and lower limb. Symmetrical involvement of the upper and the lower limbs is unusual in most cases of JE.

CONCLUSION: This case highlights the importance of awareness on the part of the clinician about the possibilities of atypical presentation in JE. It also emphasizes that Japanese encephalitis should be a part of the differential in patients with atypical neurological presentation in endemic areas.}, } @article {pmid40212027, year = {2025}, author = {Menezes, AT and Nagasse, HY and Lopes, HRM and Coltri, PP}, title = {Design of a GFP reporter for splicing analysis in mammalian cells.}, journal = {Biotechnology reports (Amsterdam, Netherlands)}, volume = {46}, number = {}, pages = {e00887}, pmid = {40212027}, issn = {2215-017X}, abstract = {Eukaryotic genes are formed by exons and introns. Pre-mRNA splicing promotes exon ligation and intron removal and is performed by a specialized macromolecular machinery named spliceosome, composed of five small ribonucleoprotein particles (snRNPs) and more than one hundred proteins. The activity of this complex is highly accurate due to the coordinated activity of its components. Altered splicing has been related to the development of several diseases, including neurodegenerative disorders, such as amyotrophic lateral sclerosis, and different types of cancer. Detailed understanding of splicing regulation in eukaryotic cells can be achieved using splicing reporter systems. We designed a reporter plasmid suitable for splicing analysis in cultured mammalian cells. Our reporter is based on GFP expression, and the splicing outcome can be easily visualized by fluorescence microscopy. We quantified splicing activity in two human cell lines, HEK-293T and MDA-MB-231, confirming its suitability for use in live cells in culture.}, } @article {pmid40210846, year = {2025}, author = {Joyce, EE and Yin, W and Löf, M and Wirdefeldt, K and Sandin, S and Fang, F}, title = {Mediterranean dietary pattern and risk of neurodegenerative diseases in a cohort of Swedish women.}, journal = {NPJ Parkinson's disease}, volume = {11}, number = {1}, pages = {71}, pmid = {40210846}, issn = {2373-8057}, support = {R01 TS000324/TS/ATSDR CDC HHS/United States ; 802091/ERC_/European Research Council/International ; 2019-01088//Vetenskapsrådet/ ; R01TS000324-01-00/CC/CDC HHS/United States ; }, abstract = {Mediterranean dietary patterns (MDP) may be neuroprotective. Using a large population-based cohort of 42,582 Swedish women, this study examined the association between MDP adherence and the risk of Parkinson's disease (PD), Alzheimer's disease (AD), and amyotrophic lateral sclerosis (ALS). During 1991-1992, women in the Women's Lifestyle and Health Study reported dietary intake, and MDP adherence was calculated. Incident neurodegenerative diseases were identified using the Swedish National Patient Register through 2022. Women who reported high MDP adherence had a lower risk of PD (HR: 0.69, 95% CI: 0.49-0.95), primarily over age 60 (HR: 0.68, 95% CI: 0.47-0.97). A moderate-high MDP adherence was associated with a lower risk of ALS before age 60 (HR: 0.44, 95% CI: 0.19-0.99), but not overall. We observed no association between MDP adherence and AD. Our findings suggest higher adherence to a MDP may be protective against PD above age 60, and ALS before age 60.}, } @article {pmid40210682, year = {2025}, author = {Perciballi, E and Bovio, F and Ferro, S and Forcella, M and Rosati, J and Carletti, RM and D'Anzi, A and Gelati, M and La Bella, V and Innocenti, M and Spataro, R and Pecoraro, M and Lombardi, I and Vulcano, E and Ruotolo, G and Mercurio, S and Sabatelli, M and Lattante, S and Malm, T and Ohtonen, S and Vescovi, AL and Fusi, P and Ferrari, D}, title = {Mitochondrial and energy metabolism dysfunctions are hallmarks of TDP-43[G376D] fibroblasts from members of an Amyotrophic Lateral Sclerosis family.}, journal = {Cell death & disease}, volume = {16}, number = {1}, pages = {272}, pmid = {40210682}, issn = {2041-4889}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology ; *Fibroblasts/metabolism/pathology ; *DNA-Binding Proteins/genetics/metabolism ; *Mitochondria/metabolism/pathology/genetics ; *Energy Metabolism/genetics ; Male ; Female ; Middle Aged ; Mutation/genetics ; Glycolysis ; Pedigree ; Adult ; Cell Proliferation ; }, abstract = {Amyotrophic Lateral Sclerosis (ALS) is an incurable neurodegenerative disease, causing degeneration of motor neurons, paralysis, and death. About 5-10% of cases are associated with gene mutations inherited from a family member (fALS). Among them, mutations in the transactive-response (TAR)-DNA-binding protein (TARDBP), which encodes for the TAR DNA binding protein 43 (TDP-43) are responsible for 4-5% of fALS but the molecular mechanisms that initiate and sustain the neurodegenerative process are largely unknown. Metabolic impairments might be involved in the pathogenesis of ALS and are currently under investigation. In order to correlate biochemical and metabolic alterations with disease progression, here, we established the metabolic fingerprint of dermal fibroblasts derived from symptomatic and asymptomatic members of a family with fALS cases carrying to the p.G376D mutation in TDP-43. We found that increased proliferation, unbalanced oxidative homeostasis and higher ATP production rate coupled with enhanced metabolic activity are underlying traits of this family. Fibroblasts from carrier individuals deploy several mechanisms to increase mitochondrial respiration to meet increasing energy demands. This is accompanied by an upregulation of glycolysis corresponding to a metabolic reprograming towards a glycolytic phenotype for ATP production during ALS progression, particularly in late disease stages. In summary, we uncover alterations in energy metabolism in TDP43[G376D] patient-derived primary fibroblasts that may be used as risk biomarkers and/or to monitor ALS progression.}, } @article {pmid40209696, year = {2025}, author = {Hawas, Y and Hamad, AA and Meshref, M and Elbehary, M and Mohamed, RG and Elshahat, A and Mabrouk, MA and Nashwan, AJ and Fouda, BH}, title = {Clinical Features, Diagnostic Implications, and Outcomes of Amyotrophic Lateral Sclerosis and Myasthenia Gravis Overlap Syndrome: A Systematic Review.}, journal = {Medical principles and practice : international journal of the Kuwait University, Health Science Centre}, volume = {}, number = {}, pages = {1-11}, pmid = {40209696}, issn = {1423-0151}, abstract = {OBJECTIVE: This review aimed to summarize the current evidence of reported myasthenia gravis (MG) and amyotrophic lateral sclerosis (ALS) overlap syndrome regarding clinical and laboratory features, diagnostic implications, management, outcomes, and comorbid conditions to raise awareness among healthcare providers and aid in proper care provision.

METHODS: Recently, a few cases of an unusual association between both diseases have been reported. PubMed, Scopus, and Web of Science were searched from inception until May 2024 to identify eligible studies. After the screening and data extraction, 20 studies with 42 cases suffering from ALS and MG were included.

RESULTS: Forty-two cases were categorized into four groups as follows: the first group had 26 cases with MG onset (age range 26-82 years) preceding ALS (age range 46-83 years). The second group had 9 cases with ALS onset (age range 34-89 years) preceding MG (age range 40-89 years). The third group comprised 5 cases of ALS with positive acetylcholine receptor antibodies but without clinical manifestations of MG. The fourth group involved 2 cases of ALS with initial ocular symptoms that were unresponsive to MG treatments.

CONCLUSION: The onset of new ptosis or diplopia in ALS patients should prompt clinicians to consider the possibility of a coexisting condition or alternative diagnosis. Additionally, positive acetylcholine receptor antibodies alone are insufficient to diagnose MG if ALS coexists. In patients with ALS, repetitive nerve stimulation tests may be less sensitive for detecting MG. Thus, diagnosing MG in ALS patients should rely on clinical presentation and response to empirical treatment.}, } @article {pmid40209306, year = {2025}, author = {Meanti, R and Bresciani, E and Rizzi, L and Molteni, L and Coco, S and Omeljaniuk, RJ and Torsello, A}, title = {Cannabinoid Receptor 2 (CB2R) as potential target for the pharmacological treatment of neurodegenerative diseases.}, journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie}, volume = {186}, number = {}, pages = {118044}, doi = {10.1016/j.biopha.2025.118044}, pmid = {40209306}, issn = {1950-6007}, mesh = {Humans ; *Receptor, Cannabinoid, CB2/metabolism/agonists ; *Neurodegenerative Diseases/drug therapy/metabolism ; Animals ; Endocannabinoids/metabolism ; Molecular Targeted Therapy ; Cannabinoid Receptor Agonists/therapeutic use ; }, abstract = {The endocannabinoid system (ECS) is a ubiquitous physiological system that plays a crucial role in maintaining CNS homeostasis and regulating its functions. It includes cannabinoid receptors (CBRs), endogenous cannabinoids (eCBs), and the enzymes responsible for their synthesis and degradation. In recent years, growing evidence has highlighted the therapeutic potential of the ECS and CBRs, in a wide range of severe diseases and pathological conditions, including Alzheimer's and Parkinson's diseases, Amyotrophic Lateral Sclerosis, Multiple Sclerosis, Huntington's Disease, HIV-1 associated neurocognitive disorders, neuropathic pain and migraine. Targeting the cannabinoid type 2 receptor (CB2R) has gained attention due to its ability to (i) mitigate neuroinflammatory responses, (ii) regulate mitochondrial function and (iii) provide trophic support, all without eliciting the psychotropic actions associated with CB1R activation. This review aims to explore the potential of CB2R modulation as a strategy for the prevention and treatment of neurologic disorders, exploring both preclinical and clinical findings.}, } @article {pmid40207633, year = {2025}, author = {Luteijn, MJ and Bhaskar, V and Trojer, D and Schürz, M and Mahboubi, H and Handl, C and Pizzato, N and Pfeifer, M and Dafinca, R and Voshol, H and Giorgetti, E and Manneville, C and Garnier, IPM and Müller, M and Zeng, F and Buntin, K and Markwalder, R and Schröder, H and Weiler, J and Khar, D and Schuhmann, T and Groot-Kormelink, PJ and Keller, CG and Farmer, P and MacKay, A and Beibel, M and Roma, G and D'Ario, G and Merkl, C and Schebesta, M and Hild, M and Elwood, F and Vahsen, BF and Ripin, N and Clery, A and Allain, F and Labow, M and Gabriel, D and Chao, JA and Talbot, K and Nash, M and Hunziker, J and Meisner-Kober, NC}, title = {High-throughput screen of 100 000 small molecules in C9ORF72 ALS neurons identifies spliceosome modulators that mobilize G4C2 repeat RNA into nuclear export and repeat associated non-canonical translation.}, journal = {Nucleic acids research}, volume = {53}, number = {7}, pages = {}, pmid = {40207633}, issn = {1362-4962}, support = {EFRE/IWB 20102-F1900731-KZP//European Funds for Regional Development/ ; WISS2025 F2200397-KZP//Salzburger Landesregierung/ ; }, mesh = {Humans ; *Spliceosomes/drug effects/metabolism/genetics ; *C9orf72 Protein/genetics ; *Amyotrophic Lateral Sclerosis/genetics/pathology/metabolism ; *Protein Biosynthesis/drug effects ; Active Transport, Cell Nucleus/drug effects ; Serine-Arginine Splicing Factors/metabolism ; *Neurons/metabolism/drug effects ; High-Throughput Screening Assays ; *Small Molecule Libraries/pharmacology ; DNA Repeat Expansion ; RNA/metabolism/genetics ; Induced Pluripotent Stem Cells/metabolism ; Cell Nucleus/metabolism ; }, abstract = {An intronic G4C2 repeat expansion in the C9ORF72 gene is the major known cause for Amyotrophic Lateral Sclerosis (ALS), with current evidence for both, loss of function and pathological gain of function disease mechanisms. We screened 96 200 small molecules in C9ORF72 patient iPS neurons for modulation of nuclear G4C2 RNA foci and identified 82 validated hits, including the Brd4 inhibitor JQ1 as well as novel analogs of Spliceostatin-A, a known modulator of SF3B1, the branch point binding protein of the U2-snRNP. Spliceosome modulation by these SF3B1 targeted compounds recruits SRSF1 to nuclear G4C2 RNA, mobilizing it from RNA foci into nucleocytoplasmic export. This leads to increased repeat-associated non-canonical (RAN) translation and ultimately, enhanced cell toxicity. Our data (i) provide a new pharmacological entry point with novel as well as known, publicly available tool compounds for dissection of C9ORF72 pathobiology in C9ORF72 ALS models, (ii) allowing to differentially modulate RNA foci versus RAN translation, and (iii) suggest that therapeutic RNA foci elimination strategies warrant caution due to a potential storage function, counteracting translation into toxic dipeptide repeat polyproteins. Instead, our data support modulation of nuclear export via SRSF1 or SR protein kinases as possible targets for future pharmacological drug discovery.}, } @article {pmid40205152, year = {2025}, author = {Mohan, M and Mannan, A and Singh, TG}, title = {Unravelling the role of protein kinase R (PKR) in neurodegenerative disease: a review.}, journal = {Molecular biology reports}, volume = {52}, number = {1}, pages = {377}, pmid = {40205152}, issn = {1573-4978}, mesh = {Humans ; *eIF-2 Kinase/metabolism/genetics ; *Neurodegenerative Diseases/metabolism/genetics ; Animals ; Parkinson Disease/metabolism/genetics ; Huntington Disease/genetics/metabolism ; Alzheimer Disease/metabolism/genetics ; Mitochondria/metabolism ; }, abstract = {Protein Kinase R is an essential regulator of many cell activities and belongs to one of the largest and most functionally complex gene families. These are found all over the body, and by adding phosphate groups to the substrate proteins, they regulate their activity and coordinate the action of almost all cellular processes. Recent research has illuminated the involvement of PKR in the pathogenesis of neurodegenerative disorders (NDs), thereby expanding our understanding of intricate molecular mechanisms underlying disease progression. Through their inhibition or activation, they hold potential therapeutic targets for the pathogenesis or protection of NDs. In the case of AD (AD), PKR contributes to the protection or elevation of Aβ accumulation, neuroinflammation, synaptic plasticity alterations, and neuronal excitability. Similarly, in Parkinson's disease (PD), PKR again has a dual role in dopaminergic neuronal loss, gene mutations, and mitochondrial dysfunction via various pathways. Notably, neuronal excitotoxicity, as well as genetic mutations, have been linked to ALS. In Huntington's disease (HD), PKR is associated with decreased or increased mutated genes, striatal neuron degeneration, neuroinflammation, and excitotoxicity. This review emphasizes strategies that target PKR for the treatment of neurodegenerative disorders. Doing so offers valuable insights that can guide future research endeavors and the development of innovative therapeutic approaches.}, } @article {pmid40204975, year = {2025}, author = {Wolmer, PS and de Borba, FC and de Rezende, TJR and González-Salazar, C and Pedroso, JL and Barsottini, OGP and Kleinerova, J and Bede, P and Marques, W and França, MC}, title = {Distinct patterns of cerebral and spinal pathology along the spectrum of ATXN2-related disorders.}, journal = {Journal of neurology}, volume = {272}, number = {5}, pages = {330}, pmid = {40204975}, issn = {1432-1459}, support = {2013/07559-3//Fundação de Amparo à Pesquisa do Estado de São Paulo/ ; }, mesh = {Humans ; Male ; *Ataxin-2/genetics ; Female ; Middle Aged ; *Spinocerebellar Ataxias/pathology/genetics/diagnostic imaging ; *Amyotrophic Lateral Sclerosis/pathology/genetics/diagnostic imaging ; Adult ; Magnetic Resonance Imaging ; Aged ; *Spinal Cord/pathology/diagnostic imaging ; *Brain/pathology/diagnostic imaging ; Neuroimaging ; }, abstract = {BACKGROUND: The ATXN2 gene contains a polymorphic CAG-rich region encoding a polyglutamine tract in ataxin- 2. Normal alleles have fewer than 27 CAG repeats, 27-34 repeats pose a risk for ALS (ATXN2-ALS), and > 34 repeats cause spinocerebellar ataxia type 2 (SCA2). The striking phenotypic differences between these two ATXN2-related conditions are not yet fully understood.

OBJECTIVE: To characterize and compare the distinguishing radiological signatures of ATXN2-ALS, SCA2, sporadic ALS (sALS) and healthy controls in vivo using quantitative computational neuroimaging techniques.

METHODS: Four groups were defined: healthy controls (n = 34), sALS (n = 17), ATXN2-ALS (n = 16), and SCA2 (n = 17). Cortical, subcortical, brainstem, cerebellar and spinal regions were segmented based on T1-weighted data using validated segmentation tools and their volumes estimated. Group-specific morphometric data were correlated with cerebral ATXN2 expression maps from the Allen Human Brain Atlas.

RESULTS: Study groups were age and sex-matched. sALS, ATXN2-ALS and SCA2 have distinct structural CNS signatures, with disease burden restricted to the precentral gyri in the sALS group, to the spinal cord and brainstem in the ATXN2-ALS group and more diffusely distributed in the subcortical structures in the SCA2 group. Brain ATXN2 expression correlated with the structural signature of SCA2, but not with that of ATXN2-ALS.

CONCLUSIONS: Neuroimaging signatures differ in ATXN2-ALS and SCA2, indicating distinct mechanisms of ATXN2-mediated neurodegeneration. sALS and ATXN2-ALS also exhibit distinct patterns of CNS involvement. The unique imaging signatures and clinical profiles along the spectrum of ATXN2-related disorders raise important questions regarding the pathophysiology of the disease and have practical clinical ramifications.}, } @article {pmid40204667, year = {2025}, author = {Parajuli, S and McDonald, MR and Adhikari, L and Wolyn, DJ}, title = {Genetic architecture of anthocyanin pigment traits and purple spot (Stemphylium vesicarium) resistance in an F1 pseudo-testcross population of asparagus.}, journal = {The plant genome}, volume = {18}, number = {2}, pages = {e70028}, pmid = {40204667}, issn = {1940-3372}, support = {ASC-18/19//Canadian Agri-Science Cluster for Horticulture 3/ ; //Asparagus Farmers of Ontario/ ; //Agriculture and Agri-Food Canada/ ; UofGT2-2019-27360//Ontario Ministry of Agriculture Food and Rural Affairs/ ; }, mesh = {*Anthocyanins/genetics/metabolism ; Quantitative Trait Loci ; *Plant Diseases/microbiology/genetics ; *Disease Resistance/genetics ; *Asparagus Plant/genetics/microbiology/metabolism ; *Ascomycota/pathogenicity/physiology ; Phenotype ; Crosses, Genetic ; Plant Leaves/genetics/microbiology ; }, abstract = {Stemphylium vesicarium (Wallr.) Simmons is a plant pathogenic fungus causing purple spot in both fern and spears of asparagus (Asparagus officinalis L.). Although the fern can be sprayed with fungicides to control the disease, pesticide applications during spear harvest are restricted. Infected spears can develop prominent pigmentation at lesion sites, reducing marketable yield. Breeding resistant asparagus cultivars with decreased lesion numbers and reduced purpling at the site of infection is considered the most economical and sustainable approach to combat this disease. The objectives of this study were to determine the genetic architectures of, and relationships among, anthocyanin pigment expression in spear scale leaves (ALS) and spear lesions (APS) and purple spot levels in spears (NPS) and fern (PSF). Traits were phenotyped over 2 years under natural conditions in an F1 pseudo-testcross population, and quantitative trait loci (QTL) were mapped. ALS, APS, NPS, and PSF were not correlated, suggesting independent regulation of the anthocyanin pathway in scale leaves and lesions and no relationship between pigment and disease. Segregation, 3 red:1 purple and 3 red:13 purple, was observed in scale leaves and lesions, respectively. Two stable QTL for each of ASL, APS, and NPS, one tentative QTL for ASL, four tentative QTL for APS, two tentative QTL for NPS, and three tentative QTL for PSF were identified. Candidate genes were found for four loci. This study advances the genetic understanding of anthocyanin pigmentation at a tissue-specific level, and purple spot disease severity in spears and fern, supporting future breeding efforts.}, } @article {pmid40203833, year = {2025}, author = {Shen, D and Vincent, A and Udine, E and Buhidma, Y and Anoar, S and Tsintzas, E and Maeland, M and Xu, D and Carcolé, M and Osumi-Sutherland, D and Aleyakpo, B and Hull, A and Martínez Corrales, G and Woodling, N and Rademakers, R and Isaacs, AM and Frigerio, C and van Blitterswijk, M and Lashley, T and Niccoli, T}, title = {Differential neuronal vulnerability to C9orf72 repeat expansion driven by Xbp1-induced endoplasmic reticulum-associated degradation.}, journal = {Cell reports}, volume = {44}, number = {4}, pages = {115459}, doi = {10.1016/j.celrep.2025.115459}, pmid = {40203833}, issn = {2211-1247}, mesh = {Animals ; *Neurons/metabolism/pathology ; *C9orf72 Protein/genetics/metabolism ; *X-Box Binding Protein 1/metabolism/genetics ; *Drosophila Proteins/metabolism/genetics ; Drosophila melanogaster/metabolism/genetics ; *Endoplasmic Reticulum/metabolism ; *DNA Repeat Expansion/genetics ; Humans ; Unfolded Protein Response ; Disease Models, Animal ; Amyotrophic Lateral Sclerosis/genetics/pathology/metabolism ; Proteolysis ; DNA-Binding Proteins ; }, abstract = {Neurodegenerative diseases are characterized by the localized loss of neurons. Why cell death is triggered only in specific neuronal populations and whether it is the response to toxic insults or the initial cellular state that determines their vulnerability is unknown. To understand individual cell responses to disease, we profiled their transcriptional signatures throughout disease development in a Drosophila model of C9orf72 (G4C2) repeat expansion (C9), the most common genetic cause of frontotemporal dementia and amyotrophic lateral sclerosis. We identified neuronal populations specifically vulnerable or resistant to C9 expression and found an upregulation of protein homeostasis pathways in resistant neurons at baseline. Overexpression of Xbp1s, a key regulator of the unfolded protein response and a central node in the resistance network, rescues C9 toxicity. This study shows that neuronal vulnerability depends on the intrinsic transcriptional state of neurons and that leveraging resistant neurons' properties can boost resistance in vulnerable neurons.}, } @article {pmid40203806, year = {2025}, author = {Johnson, AM and Lukens, JR}, title = {Glia get RIPped in ALS.}, journal = {Immunity}, volume = {58}, number = {4}, pages = {778-780}, doi = {10.1016/j.immuni.2025.03.013}, pmid = {40203806}, issn = {1097-4180}, support = {F31 AG089911/AG/NIA NIH HHS/United States ; RF1 AG078684/AG/NIA NIH HHS/United States ; T32 NS115657/NS/NINDS NIH HHS/United States ; R01 AG087406/AG/NIA NIH HHS/United States ; R01 AG071996/AG/NIA NIH HHS/United States ; }, mesh = {*Amyotrophic Lateral Sclerosis/immunology/pathology/metabolism ; Humans ; Animals ; *Neuroglia/immunology/metabolism ; *Receptor-Interacting Protein Serine-Threonine Kinases/metabolism/immunology ; *Microglia/immunology/metabolism ; *Astrocytes/immunology/metabolism ; Mice ; Neuroinflammatory Diseases/immunology ; Disease Models, Animal ; }, abstract = {While neuroinflammatory responses driven by microglia and astrocytes have been extensively linked to neurodegenerative disease progression in amyotrophic lateral sclerosis (ALS), the specific pathways that coordinate glial cell-dependent neuroinflammation in ALS remain poorly defined. In this issue of Immunity, Zelic et al.[1] identified RIPK1 as a pivotal regulator of glial cell-driven neuroinflammation in multiple ALS models.}, } @article {pmid40202986, year = {2025}, author = {Askarova, A and Yaa, RM and Marzi, SJ and Nott, A}, title = {Genetic risk for neurodegenerative conditions is linked to disease-specific microglial pathways.}, journal = {PLoS genetics}, volume = {21}, number = {4}, pages = {e1011407}, pmid = {40202986}, issn = {1553-7404}, mesh = {Humans ; *Microglia/metabolism/pathology ; *Genetic Predisposition to Disease ; Genome-Wide Association Study ; *Neurodegenerative Diseases/genetics/pathology ; Schizophrenia/genetics/pathology ; Neurons/metabolism/pathology ; Alzheimer Disease/genetics/pathology ; Multiple Sclerosis/genetics/pathology ; Parkinson Disease/genetics/pathology ; Oligodendroglia/metabolism/pathology ; Chromatin/genetics ; Linkage Disequilibrium/genetics ; Amyotrophic Lateral Sclerosis/genetics/pathology ; Promoter Regions, Genetic/genetics ; Brain/metabolism/pathology ; Polymorphism, Single Nucleotide ; }, abstract = {Genome-wide association studies have identified thousands of common variants associated with an increased risk of neurodegenerative disorders. However, the noncoding localization of these variants has made the assignment of target genes for brain cell types challenging. Genomic approaches that infer chromosomal 3D architecture can link noncoding risk variants and distal gene regulatory elements such as enhancers to gene promoters. By using enhancer-to-promoter interactome maps for human microglia, neurons, and oligodendrocytes, we identified cell-type-specific enrichment of genetic heritability for brain disorders through stratified linkage disequilibrium score regression. Our analysis suggests that genetic heritability for multiple neurodegenerative disorders is enriched at microglial chromatin contact sites, while schizophrenia heritability is predominantly enriched at chromatin contact sites in neurons followed by oligodendrocytes. Through Hi-C coupled multimarker analysis of genomic annotation (H-MAGMA), we identified disease risk genes for Alzheimer's disease, Parkinson's disease, multiple sclerosis, amyotrophic lateral sclerosis and schizophrenia. We found that disease-risk genes were overrepresented in microglia compared to other brain cell types across neurodegenerative conditions and within neurons for schizophrenia. Notably, the microglial risk genes and pathways identified were largely specific to each disease. Our findings reinforce microglia as an important, genetically informed cell type for therapeutic interventions in neurodegenerative conditions and highlight potentially targetable disease-relevant pathways.}, } @article {pmid40202704, year = {2025}, author = {Oyovwi, MO and Chijiokwu, EA and Ben-Azu, B and Atere, AD and Joseph, UG and Ogbutor, UG and Udi, OA}, title = {Potential Roles of Natural Antioxidants in Modulating Neurodegenerative Disease Pathways.}, journal = {Molecular neurobiology}, volume = {62}, number = {8}, pages = {10367-10397}, pmid = {40202704}, issn = {1559-1182}, mesh = {Humans ; *Antioxidants/therapeutic use/pharmacology ; *Neurodegenerative Diseases/drug therapy/metabolism/pathology ; Animals ; Oxidative Stress/drug effects ; Neuroprotective Agents/therapeutic use/pharmacology ; *Signal Transduction/drug effects ; *Biological Products/therapeutic use/pharmacology ; }, abstract = {Neurodegenerative diseases, including Alzheimer's, Parkinson's, and amyotrophic lateral sclerosis, are increasingly prevalent among aging populations. Oxidative stress contributes to these diseases, leading to cellular damage and neuronal death. Natural antioxidants are being explored as preventive measures. This study aims to assess the effectiveness of natural antioxidants in delaying the onset or progression of neurodegenerative diseases by identifying their specific mechanisms of action. A comprehensive review of existing literature was conducted, focusing on studies that examine the role of natural antioxidants in neuroprotection. Key natural antioxidants, including flavonoids, polyphenls, vitamins C and E, and omega-3 fatty acids, were reviewed and analyzed for their bioavailability, mechanisms of action, and outcomes in both in vitro and in vivo studies. Additionally, clinical trials involving human subjects were considered to provide insights into the translational implications of antioxidant consumption. The findings suggest that several natural antioxidants exhibit neuroprotective properties by modulating oxidative stress, reducing inflammation, and promoting neuronal survival. For instance, flavonoids such as quercetin and resveratrol have shown promise in enhancing cognitive function and mitigating the pathophysiological alterations associated with neurodegeneration. In clinical studies, higher intakes of dietary antioxidants were correlated with a reduced risk of developing neurodegenerative disorders. Natural antioxidants offer potential for preventing neurodegenerative diseases by counteracting oxidative stress and maintaining cellular integrity. Overall, our report recommends that further research is needed to optimize dosages and understand their long-term benefits.}, } @article {pmid40202498, year = {2025}, author = {Gu, J and Yang, M and Zhang, L and Liu, Y and Yan, R and Pan, D and Qian, X and Hu, H and Chu, D and Hu, C and Liu, F and Cui, H}, title = {Rhythmic TDP-43 affects RNA splicing of USP13, resulting in alteration of BMAL1 ubiquitination.}, journal = {The Journal of cell biology}, volume = {224}, number = {5}, pages = {}, pmid = {40202498}, issn = {1540-8140}, support = {32171258//National Natural Science Foundation of China/ ; BK20211329//Natural Science Foundation of Jiangsu Province/ ; //Co-Innovation Center of Neuroregeneration/ ; //Nantong University/ ; }, mesh = {Animals ; *ARNTL Transcription Factors/metabolism/genetics ; *DNA-Binding Proteins/metabolism/genetics ; *Ubiquitination ; *Circadian Rhythm/genetics ; Humans ; Mice ; *RNA Splicing/genetics ; *Ubiquitin-Specific Proteases/genetics/metabolism ; Mice, Inbred C57BL ; Male ; HEK293 Cells ; }, abstract = {Circadian rhythm disorders are common characteristics of neurodegenerative diseases. The pathological aggregation of transactive response DNA-binding protein 43 (TDP-43) is associated with multiple neurodegenerative diseases, such as amyotrophic lateral sclerosis. However, the relationship between TDP-43 and circadian rhythm remains unknown. Here, we found that TDP-43 is rhythmically expressed both in vivo and in vitro. TDP-43 knockdown affected the expression of circadian genes, including BMAL1, CLOCK, CRY1, and PER2, and impaired autonomous circadian wheel behavior, cognitive functions, and balance abilities in mice. Furthermore, TDP-43 knockdown induced aberrant splicing of ubiquitin-specific peptidase 13 (USP13) and blocked USP13 rhythmic expression, enhancing the ubiquitination of BMAL1. Meanwhile, TDP-43 knockdown altered the rhythmic expression of phospho-AMPKα (Thr172) and platelet-type phosphofructokinase (PFKP), which may change cellular glucose uptake and ATP production. Our findings further the understanding of the role of TDP-43 dysfunction in circadian rhythm disruption in neurodegenerative diseases and provide new mechanistic evidence supporting the interaction between circadian rhythm disruption and neurodegeneration.}, } @article {pmid40200760, year = {2025}, author = {Herrmann, C and Uzelac, Z and Michels, S and Weber, A and Richter, L and Elmas, Z and Jagodzinski, L and Wurster, C and Schuster, J and Dreyhaupt, J and Dorst, J}, title = {Alterations of Fat and Ketone Body Metabolism in ALS and SMA-A Prospective Observational Study.}, journal = {European journal of neurology}, volume = {32}, number = {4}, pages = {e70132}, pmid = {40200760}, issn = {1468-1331}, mesh = {Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; *Adipose Tissue/metabolism ; *Amyotrophic Lateral Sclerosis/metabolism ; Energy Metabolism/physiology ; Fatty Acids, Nonesterified/metabolism/blood ; *Ketone Bodies/metabolism ; *Muscular Atrophy, Spinal/metabolism ; Prospective Studies ; Young Adult ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerdosis (ALS) and spinal muscular atrophy (SMA) are motor neuron diseases associated with distinct metabolic alterations. ALS patients feature an increased resting energy expenditure (REE) causing weight loss and cachexia. In SMA, a disturbed utilization of free fatty acids has been described. These metabolic alterations negatively affect prognosis in both diseases. The objective of this study was to further characterize these changes to identify potential therapeutic targets.

METHODS: Between 11/2020 and 08/2022, 112 ALS patients, 77 SMA patients, and 50 controls were recruited in the Department of Neurology of Ulm University. Standardized blood and urinary samples were collected to analyze fat and ketone metabolism.

RESULTS: Ketone body levels were higher in ALS and SMA compared to controls. In both diseases, patients with higher BMI featured higher ketone bodies and free fatty acids compared to those with lower BMI, while in controls we found the opposite phenomenon. In SMA, more severe disease types were associated with higher ketone body levels. Compared to ALS, SMA patients featured higher ketone body and free fatty acid levels.

CONCLUSIONS: Our data suggest that already during early disease stages, ALS patients produce ketone bodies to compensate for the energy deficit. In SMA, on the other hand, the persistence of ketogenesis may indicate an upregulation of all available metabolic pathways for energy production due to the disturbance of fatty acid utilization. Therefore, the application of additional sources of energy, such as ketone bodies, might constitute a promising therapeutic option in both diseases.}, } @article {pmid40200577, year = {2025}, author = {Winkelsas, A and Apfel, A and Johnson, B and Harmison, G and Perez, KD and Li, D and Cheung, VG and Grunseich, C}, title = {Allele-specific silencing of a dominant SETX mutation in familial amyotrophic lateral sclerosis type 4.}, journal = {HGG advances}, volume = {6}, number = {3}, pages = {100435}, pmid = {40200577}, issn = {2666-2477}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/pathology ; *Alleles ; HEK293 Cells ; *Mutation ; *RNA Helicases/genetics ; *Multifunctional Enzymes/genetics ; RNA, Small Interfering/genetics ; *Gene Silencing ; DNA Helicases/genetics ; RNA Interference ; }, abstract = {Amyotrophic lateral sclerosis 4 (ALS4) is an autosomal dominant motor neuron disease that is molecularly characterized by reduced R-loop levels and caused by pathogenic variants in senataxin (SETX). SETX encodes an RNA/DNA helicase that resolves three-stranded nucleic acid structures called R-loops. Currently, there are no disease-modifying therapies available for ALS4. Given that SETX is haplosufficient, removing the product of the mutated allele presents a potential therapeutic strategy. We designed a series of siRNAs to selectively target the RNA transcript from the ALS4 allele containing the c.1166T>C mutation (p.Leu389Ser). Transfection of HEK293 cells with siRNA and plasmids encoding either wild-type or mutant (Leu389Ser) epitope-tagged SETX revealed that three siRNAs specifically reduced mutant SETX protein levels while having minimal effect on the wild-type SETX protein. In ALS4 primary fibroblasts, siRNA treatment silenced the endogenous mutant SETX allele while sparing the wild-type allele and restored R-loop levels in patient cells. Our findings demonstrate that mutant SETX, differing from wild-type by a single nucleotide, can be effectively and specifically silenced by RNA interference.}, } @article {pmid40200520, year = {2025}, author = {Nikiema, SLW and Barro, SG and Kantagba, YMK and Kouraogo, BAJ and Staccini, P}, title = {Design and Development of a Virtual Reality Tool for Adult Basic Life Support Training.}, journal = {Studies in health technology and informatics}, volume = {323}, number = {}, pages = {414-418}, doi = {10.3233/SHTI250123}, pmid = {40200520}, issn = {1879-8365}, mesh = {*Virtual Reality ; Humans ; *Cardiopulmonary Resuscitation/education/instrumentation ; Adult ; *User-Computer Interface ; }, abstract = {The research introduces a Virtual Reality (VR) instrument for Adult Basic Life Support (ABLS) training, employing Blender for 3D modeling, Unity3D for VR environment creation, XChart for data visualization, and the Oculus Quest 2 as the principal VR headset. The device replicates authentic emergency situations, offering immediate feedback on CPR execution. Preliminary findings indicate enhancements in technical proficiency and user engagement; nonetheless, issues like as motion sickness and scalability remain unresolved. Future improvements will concentrate on sophisticated haptic feedback and ALS scenarios.}, } @article {pmid40200352, year = {2025}, author = {Li, J and Tang, S and Li, J and Huang, X and Liu, Y and Zeng, J and Fan, Y}, title = {Incidence and health burden of 20 rare neurological diseases in South China from 2016 to 2022: a hospital-based observational study.}, journal = {Orphanet journal of rare diseases}, volume = {20}, number = {1}, pages = {163}, pmid = {40200352}, issn = {1750-1172}, support = {202007030010//Guangzhou Science and Technology Program Key Projects/ ; 2020B1212060017//Guangdong Provincial Key Laboratory of Diagnosis and Treatment of Major Neurological Diseases/ ; 2020B1111170002//Guangdong Provincial Clinical Research Center for Neurological Diseases/ ; }, mesh = {Humans ; China/epidemiology ; Male ; Female ; *Nervous System Diseases/epidemiology ; Incidence ; Adult ; Middle Aged ; *Rare Diseases/epidemiology ; Adolescent ; Child ; Aged ; Young Adult ; Hospitals ; }, abstract = {BACKGROUND: Rare neurological diseases (RNDs) result in severe health burdens worldwide. Data from China are limited. We aimed to investigate the health burden of 20 RNDs in Guangdong Province (GD), which contains two-thirds of the population of South China.

METHODS: The hospitalization data of 20 RNDs were described using hospital-based front sheet data from 3,037 hospitals of GD from 2016 to 2022. The 20 RNDs included amyotrophic lateral sclerosis (ALS), Charcot-Marie-Tooth Disease, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, congenital myotonia, congenital myasthenic syndrome, Dravet syndrome, Fabry disease, hereditary spastic paraplegia, Huntington disease, Leber hereditary optic neuropathy, mitochondrial encephalopathy (ME), multi-focal motor neuropathy, myotonic dystrophy, primary hereditary dystonia, progressive muscular dystrophy (PMD), spinal and bulbar muscular atrophy, spinal muscular atrophy (SMA), spinocerebellar ataxia, Wilson disease (WD) and X-linked adrenoleukodystrophy. Age were presented as mean and standard deviation while length of hospital stay as median and interquartile range (25th and 75th percentiles). The other variables were described as number and percentage. The data were analyzed by Joinpoint regression.

RESULTS: There were 9,351 cases, including 330 ICU and 155 death cases. The average age was 33.7 ± 22.0 y, and 63.8% of patients were male. From 2016 to 2022, the number of RND (and juvenile RND) cases were 1034 (184), 1174 (293), 1443 (374), 1422 (320), 1331 (337), 1432 (409) to 1515 (515). ICU (and juvenile ICU) cases rose from 28 (3), 34 (6), 24 (4), 38 (11), 46 (13), 54 (24) to 106 (56). Joinpoint regression showed significant upward trend in percentages of juvenile and juvenile ICU cases (APC = 8.13, P< 0.05; APC = 28.42, P< 0.05). The fop five RNDs were WD, ASL, PMD, ME, and SMA, which accounted for 79.7% of all, 99.1% of ICU, and 94.8% of death cases.

CONCLUSIONS: We demonstrated that the increase in health burden of RNDs was mainly evident in juveniles in South China from 2016 to 2022. The top 5 RNDs accounted for majority of the critical patients.}, } @article {pmid40199586, year = {2025}, author = {Fyrberg, E and Learnard, H and Lee, S and Jun, YW and Gao, FB}, title = {New Mouse Lines That Drive Tetracycline-Controlled Gene Expression in a Small Subset of Spinal Cord Dorsal Horn Neurons.}, journal = {eNeuro}, volume = {12}, number = {4}, pages = {}, pmid = {40199586}, issn = {2373-2822}, support = {R01 NS101986/NS/NINDS NIH HHS/United States ; RF1 AG082478/AG/NIA NIH HHS/United States ; }, mesh = {Animals ; *Posterior Horn Cells/metabolism/drug effects ; *Tetracycline/pharmacology ; Mice, Transgenic ; Mice ; Promoter Regions, Genetic ; Disease Models, Animal ; Amyotrophic Lateral Sclerosis/genetics/metabolism ; *Gene Expression/drug effects ; Spinal Cord/metabolism ; Mice, Inbred C57BL ; Transcription Factors ; Homeodomain Proteins ; }, abstract = {Mouse lines with tetracycline-controlled gene expression in specific neuronal populations provide valuable tools for studying their development, function, connectivity, and pathology in vivo. Our initial goal was to generate a mouse model that could express amyotrophic lateral sclerosis-associated genes specifically in spinal cord motor neurons under the control of the HB9 promoter. However, HB9-tTA mice unexpectedly direct target gene expression in a small subset of dorsal horn neurons. These mice represent a new tool for scientists who are interested in studying these spinal cord neurons.}, } @article {pmid40198794, year = {2025}, author = {Corucci, G and Vadukul, DM and Paracini, N and Laux, V and Batchu, KC and Aprile, FA and Pastore, A}, title = {Membrane Charge Drives the Aggregation of TDP-43 Pathological Fragments.}, journal = {Journal of the American Chemical Society}, volume = {147}, number = {16}, pages = {13577-13591}, pmid = {40198794}, issn = {1520-5126}, mesh = {*DNA-Binding Proteins/chemistry/metabolism ; Humans ; *Lipid Bilayers/chemistry/metabolism ; Protein Aggregates ; }, abstract = {TDP-43 protein is an RNA-binding protein linked to amyotrophic lateral sclerosis, frontotemporal dementia, and Alzheimer disease. While normally a protein that shuttles between the nucleus and cytoplasm, TDP-43 has recently been found also in extracellular vesicles. These are an important medium for cell-cell communication that allows the transfer of lipids, proteins, and genetic material among cells. An increasing concern in neurodegenerative diseases, however, is the possibility that extracellular vesicles can also provide an effective way to spread misfolded proteins that could "infect" other cells according to a "prion-like" mechanism. To characterize the interaction of TDP-43 with lipid membranes, we carried out a systematic biophysical study using a TDP-43 fragment lacking the first 84 N-terminal residues, called M85, and synthetic model phospholipid membranes. We utilized standard techniques, such as fluorescence and microscopy, complemented by neutron reflectivity measurements. Our results show that lipid charge affects the modality by which M85 interacts with membranes: a higher negative charge induces the protein to bind to the bilayer surface, promoting protein aggregation and decreasing lipid bilayer damage that this interaction causes. Thus, we speculate that the M85-lipid membrane interaction could play an important and previously undefined role in TDP-43-related neurodegenerative diseases.}, } @article {pmid40198473, year = {2025}, author = {Seok, HY}, title = {Critical issues in the use of edaravone for the treatment of amyotrophic lateral sclerosis.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {46}, number = {8}, pages = {3427-3430}, pmid = {40198473}, issn = {1590-3478}, mesh = {*Amyotrophic Lateral Sclerosis/drug therapy ; Humans ; *Edaravone/therapeutic use ; *Neuroprotective Agents/therapeutic use ; *Free Radical Scavengers/therapeutic use ; Disease Progression ; Riluzole/therapeutic use ; }, abstract = {Edaravone, along with riluzole, is a key treatment for amyotrophic lateral sclerosis (ALS), with evidence supporting its efficacy in slowing disease progression, particularly in patients with early-stage ALS. Despite its approval and increasing clinical use, several critical questions about its use remain unanswered: Can edaravone be effective as monotherapy? Is it beneficial for patients who fall outside the inclusion criteria of pivotal trials? What is the optimal duration of treatment as ALS progresses? In addition, does edaravone provide clinical benefit to patients with familial ALS? Answering these questions is essential to optimize the use of edaravone in clinical practice and to further our understanding of its role in the treatment of ALS. This review synthesizes the current evidence to address these questions and identifies areas that require further investigation.}, } @article {pmid40196899, year = {2025}, author = {Li, S and Pandat, T and Chi, B and Moon, D and Mas, M}, title = {Management Approaches to Spastic Gait Disorders.}, journal = {Muscle & nerve}, volume = {72}, number = {2}, pages = {179-200}, doi = {10.1002/mus.28402}, pmid = {40196899}, issn = {1097-4598}, mesh = {Humans ; *Gait Disorders, Neurologic/therapy/etiology/diagnosis/physiopathology ; *Muscle Spasticity/therapy/complications/physiopathology/diagnosis ; *Disease Management ; }, abstract = {Spastic gait presents clinically as the net mechanical consequence of neurological impairments of spasticity, weakness, and abnormal synergies and their interactions with the ground reaction force in patients with upper motor neuron syndromes and with some neuromuscular diseases. It is critical to differentiate whether the primary problem is weakness or spasticity, thus better understanding different phenotypes of spastic gait disorders. Pelvic girdle abnormality plays a pivotal role in determining the clinical presentation of gait disorders, since it determines the body vector and compensatory kinetic chain reactions in the knee and ankle joints. Knee joint abnormality can be a mechanical compensation for hip and/or ankle and foot abnormality. Diagnostic nerve blocks and instrumented gait analysis may be needed for diagnosing the underlying problems and developing an individualized plan of care. A wide spectrum of treatment options has been used to manage spastic gait disorders. Some are in early and investigational stages, such as neuromodulation modalities, while others are well-developed, such as therapeutic exercise, ankle-foot orthoses, botulinum toxin treatment, and surgical interventions. Physicians and other healthcare providers who manage spastic gait disorders should be familiar with these treatment options and should employ appropriate interventions concurrently rather than serially. The most effective treatments can be selected based on careful evaluation, inputs from patients, family, and therapists, along with appropriate goal setting. Treatment plans need to be re-evaluated for effectiveness, relevance, and in concordance with disease progress. This is particularly important for patients with progressive neuromuscular diseases such as amyotrophic lateral sclerosis.}, } @article {pmid40196659, year = {2025}, author = {Ramesh, N and Evans, A and Wojta, K and Yang, Z and Boks, MM and Kahn, RS and de Boer, SCM and van der Lee, SJ and Pijnenburg, YAL and Reus, LM and Ophoff, RA}, title = {Accurate DNA Methylation Predictor for C9orf72 Repeat Expansion Alleles in the Pathogenic Range.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2025.03.20.643775}, pmid = {40196659}, issn = {2692-8205}, abstract = {The hexanucleotide (G 4 C 2) repeat expansion in the promoter region of C9orf72 is the most frequent genetic cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). In this study, we conducted a genome-wide DNA methylation (DNAm) analysis using EPIC version 2 (EPICv2) arrays on an FTD cohort comprising 27 carriers and 250 non-carriers of the pathogenic C9orf72 repeat expansion from the Amsterdam Dementia Cohort. We identified differentially methylated CpGs probes associated with the pathogenic C9orf72 expansion and used these findings to create a DNAm Least Absolute Shrinkage and Selection Operator (LASSO) predictor to identify repeat expansion carriers. Eight CpG sites at the C9orf72 locus were significantly differentially hypermethylated in repeat expansion carriers compared to non-carriers. The LASSO model predicted repeat expansion status with an average accuracy of 98.6%. The LASSO predictor was further validated in an independent cohort of 2,548 subjects with available EPICv2 data, identifying four C9orf72 repeat expansion carriers, subsequently confirmed by repeat-primed PCR. This result not only illustrates the accuracy of the DNAm predictor of C9orf72 repeat expansion carriers but also suggests that repeat expansion carriers may be more prevalent than expected. The identification of a highly accurate DNAm biomarker for a repeat expansion locus associated with neurodegenerative disorders may provide great value for studying this locus. The approach holds significant promise for investigating this and other repeat expansion loci, particularly given the growing interest in epigenetic epidemiological studies involving large cohorts with available DNAm data.}, } @article {pmid40196013, year = {2025}, author = {Viteri, JA and Kerr, NR and Brennan, CD and Kick, GR and Wang, M and Ketabforoush, A and Snyder, HK and Moore, PJ and Darvishi, FB and Dashtmian, AR and Ayyagari, SN and Rich, K and Zhu, Y and Arnold, WD}, title = {Targeting senescence in Amyotrophic Lateral Sclerosis: senolytic treatment improves neuromuscular function and preserves cortical excitability in a TDP-43[Q331K] mouse model.}, journal = {Research square}, volume = {}, number = {}, pages = {}, pmid = {40196013}, issn = {2693-5015}, support = {R01 AG078129/AG/NIA NIH HHS/United States ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder marked by progressive motor neuron degeneration in the primary motor cortex (PMC) and spinal cord. Aging is a key factor in ALS onset and progression, with evidence suggesting that biological aging-a process involving cellular decline- far outpaces chronological aging in ALS. This promotes senescent cell accumulation-marked by irreversible cell-cycle arrest, impaired apoptosis, and chronic inflammation-disrupting tissue homeostasis and impairing neuronal support functions. Thus, targeting senescence presents a novel therapeutic strategy for ALS. Here, we investigated the senolytic combination Dasatinib and Quercetin (D&Q) in TDP-43[Q331K] ALS mice. D&Q improved neuromuscular function and reduced plasma neurofilament light chain, a biomarker of axonal damage. The most pronounced improvement was the improved cortical excitability, accompanied by reductions in senescence and TDP-43 in the PMC. These findings highlight the potential of senolytics to mitigate ALS-related dysfunction, supporting their viability as a therapeutic strategy.}, } @article {pmid40192904, year = {2025}, author = {Kodirov, SA}, title = {Comparison of Superoxide Dismutase Activity at the Cell, Organ, and Whole-Body Levels.}, journal = {Cell biochemistry and biophysics}, volume = {}, number = {}, pages = {}, pmid = {40192904}, issn = {1559-0283}, abstract = {Superoxide dismutase (SOD) can be considered an antitoxic metalloenzyme that facilitates the production of oxygen and hydrogen peroxide from superoxide anions. Four classes have been identified depending on selective binding of metals, namely Cu,Zn-SOD, Fe-SOD, Mn-SOD, and Ni-SOD. The established isoforms are SOD1, SOD2, and SOD3 in various cells and tissues of eukaryotes. The relatively newer type Ni-SOD binds nickel and is observed in bacteria, including the genus Streptomyces. The Fe-SOD and Mn-SOD are also present in bacteria. Cu,Zn superoxide dismutase (SOD1) activity correlates with various pathophysiological states of organs. SOD2 binds manganese (Mn) and is located in the mitochondria. The SOD3, similar to the SOD1, binds copper and zinc, which are also expressed in the brain. The assay relies on several methods, including the enzyme activities, expression, field potential, and patch-clamp electrophysiology. The effects of SOD activity are emphasized at organ and whole-body levels depending on animal models. The antioxidant properties and behavior of SOD are compared based on responses among females and males to diet and toxic substances. However, in humans with amyotrophic lateral sclerosis (ALS), the mean SOD activity in both erythrocytes and muscles was comparable to controls. The detailed comparisons between the catalase and SOD activities are one of the aspects of this review. Also, modulation of excitability and synaptic plasticity in neurons by SOD is highlighted.}, } @article {pmid40192272, year = {2025}, author = {Kurashige, T and Murao, T and Kanaya, Y and Dodo, Y and Sugiura, T and Kuraoka, K and Ohshita, T}, title = {Intramuscular Nerve Bundles Reflect TDP-43 Pathology in the Medulla and Spinal Cord of ALS Patients.}, journal = {Neuropathology and applied neurobiology}, volume = {51}, number = {2}, pages = {e70016}, pmid = {40192272}, issn = {1365-2990}, support = {//SENSHIN Medical Research Foundation/ ; //ALS foundation by Japan ALS Association/ ; //Tsuchiya Foundation/ ; //Takeda Science Foundation/ ; //Japan ALS Association/ ; //Daiichi Sankyo Foundation of Life Science/ ; //Kato Memorial Trust for Nanbyo Research/ ; //Kurozumi Medical Foundation/ ; //Okinaka Memorial Institute for Medical Research/ ; //Takeda Science Foundation, and Tsuchiya Foundation/ ; }, } @article {pmid40189941, year = {2025}, author = {Padigos, J and Murray, L and Bredhauer, O and Jaspers, J and Bethune, S}, title = {Extending the interval for changing flushing solutions for central venous and arterial line systems in the intensive care unit: An evidence-based quality improvement project.}, journal = {Nursing in critical care}, volume = {30}, number = {3}, pages = {e70034}, pmid = {40189941}, issn = {1478-5153}, mesh = {Humans ; *Quality Improvement ; *Intensive Care Units/organization & administration ; Queensland ; *Catheterization, Central Venous/methods ; Time Factors ; Catheter-Related Infections/prevention & control ; }, abstract = {BACKGROUND: Central venous lines (CVLs) and arterial lines (ALs) are commonly used for patients in the intensive care units (ICUs) to facilitate the administration of medications and haemodynamic monitoring. In an ICU in Queensland, Australia (AU), saline (sodium chloride 0.9%) flush bags used for these lines were routinely changed every 24 h following organizational policy that all intravenous fluid bags are to be changed within a 24-h period.

AIM: This quality improvement (QI) project aimed to evaluate current practice guided by the Plan-Do-Study-Act (PDSA) model of QI and implementation science. Benchmarking practices with other ICUs was conducted.

STUDY DESIGN: A narrative literature review focused on evaluating the safe interval for changing flush solutions every 24 h was performed using EBSCO Medline, CINAHL, Cochrane Library, Embase and Google Scholar databases for citations up to November 2022. Bloodstream infection rates attributed to CVLs and/or ALs were monitored. Economic analysis was performed. End-user feedback was sought. A change of practice was implemented for a 1-year study period (March 2023 - March 2024) to extend dwell times of flushing solutions for CVLs and ALs from every 24 h to every 96 h.

RESULTS: One-year post-implementation, no bloodstream infections were linked to CVLs or ALs. A simplified economic analysis was performed based on costs of 0.9% sodium chloride 500-mL fluid bags, which revealed that changing the fluid bags once every 96 h resulted in a per patient saving of AU$3.21 for any individual AL or CVL and up to AU$6.42 per patient where both an AL and CVL are in situ, based on fluid bag cost at AU$1.07 per bag. This saving excludes potential savings from reduced nursing time, infection-related costs and recycling costs.

CONCLUSION: A sustainable practice change based on evidence was implemented in the local ICU. The use of the PDSA model of the QI process and the principles of implementation science strengthened the buy-in and implementation of the project.

This practice change was examined through lenses of evidence-based practice, environmental sustainability (minimizing environmental footprint by limiting plastic bag usage), patient safety, cost minimization, and reduced nursing workload.}, } @article {pmid40189519, year = {2025}, author = {Tseng, PT and Zeng, BY and Hsu, CW and Hung, CM and Carvalho, AF and Stubbs, B and Chen, YW and Chen, TY and Lei, WT and Chen, JJ and Su, KP and Shiue, YL and Liang, CS}, title = {The pharmacodynamics-based prophylactic benefits of GLP-1 receptor agonists and SGLT2 inhibitors on neurodegenerative diseases: evidence from a network meta-analysis.}, journal = {BMC medicine}, volume = {23}, number = {1}, pages = {197}, pmid = {40189519}, issn = {1741-7015}, mesh = {Humans ; *Glucagon-Like Peptide-1 Receptor Agonists/pharmacology/therapeutic use ; Hypoglycemic Agents/pharmacology/therapeutic use ; *Neurodegenerative Diseases/prevention & control/drug therapy ; Randomized Controlled Trials as Topic ; *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/pharmacology ; }, abstract = {BACKGROUND: Glucagon-like peptide-1 (GLP-1) receptor agonists and sodium-glucose cotransporter 2 (SGLT2) inhibitors represent a new generation of antihyperglycemic agents that operate through mechanisms distinct from conventional diabetes treatments. Beyond their metabolic effects, these medications have demonstrated neuroprotective properties in preclinical studies. While clinical trials have explored their therapeutic potential in established neurodegenerative conditions, their role in disease prevention remains unclear. We conducted a network meta-analysis (NMA) to comprehensively evaluate the prophylactic benefits of these agents across multiple neurodegenerative diseases and identify the most promising preventive strategies.

METHODS: We systematically searched PubMed, Embase, ClinicalKey, Cochrane CENTRAL, ProQuest, ScienceDirect, Web of Science, and ClinicalTrials.gov through October 24th, 2024, for randomized controlled trials (RCTs) of GLP-1 receptor agonists or SGLT2 inhibitors. Our primary outcome was the incidence of seven major neurodegenerative diseases: Parkinson's disease, Alzheimer's disease, Lewy body dementia, multiple sclerosis, amyotrophic lateral sclerosis, frontotemporal dementia, and Huntington's disease. Secondary outcomes included safety profiles assessed through dropout rates. We performed a frequentist-based NMA and evaluated risk of bias with Risk of Bias tool. The main result of the primary outcome in the current study would be re-affirmed via sensitivity test with Bayesian-based NMA.

RESULTS: Our analysis encompassed 22 RCTs involving 138,282 participants (mean age 64.8 years, 36.4% female). Among all investigated medications, only dapagliflozin demonstrated significant prophylactic benefits, specifically in preventing Parkinson's disease (odds ratio = 0.28, 95% confidence intervals = 0.09 to 0.93) compared to controls. Neither GLP-1 receptor agonists nor other SGLT2 inhibitors showed significant preventive effects for any of the investigated neurodegenerative conditions. Drop-out rates were comparable across all treatments.

CONCLUSIONS: This comprehensive NMA reveals a novel and specific prophylactic effect of dapagliflozin against Parkinson's disease, representing a potential breakthrough in preventive neurology. The specificity of dapagliflozin's protective effect to Parkinson's disease might rely on its highly selective inhibition to SGLT2. These findings provide important direction for future research and could inform preventive strategies for populations at risk of Parkinson's disease.

TRIAL REGISTRATION: PROSPERO CRD42021252381.}, } @article {pmid40188980, year = {2025}, author = {Chong, ZZ and Souayah, N}, title = {Pathogenic TDP-43 in amyotrophic lateral sclerosis.}, journal = {Drug discovery today}, volume = {30}, number = {5}, pages = {104351}, doi = {10.1016/j.drudis.2025.104351}, pmid = {40188980}, issn = {1878-5832}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology ; *DNA-Binding Proteins/genetics/metabolism ; Animals ; Mutation ; Protein Processing, Post-Translational ; }, abstract = {The aberrant expression of the transactive response DNA-binding protein of 43 kDa (TDP-43) has been closely associated with amyotrophic lateral sclerosis (ALS). Cytoplasmic inclusions containing TDP-43 can be found in the brain and spinal cord in up to 97% of ALS cases. Mutations in the TARDBP gene promote the nuclear export of TDP-43, increase cytoplasmic aggregation, and predispose TDP-43 to post-translational modifications. Cleavage of TDP-43 and the resulting C- and N-terminal fragments also contribute to the development of ALS. Cellularly, the resulting impairment of autophagy and mitochondria aggravates cellular damage and neurodegeneration. Given the contribution of pathogenic TDP-43 to the development of ALS, elucidating the mechanisms related to TDP-43 will facilitate finding therapeutic targets for the disease.}, } @article {pmid40188806, year = {2025}, author = {Saller, R and Schwabl, H and Rostock, M and Dal Cero, M}, title = {[Vom Spezifischen zum Systemischen - am Beispiel Tormentill/Blutwurz, der Heilpflanze des Jahres 2024].}, journal = {Complementary medicine research}, volume = {32}, number = {3}, pages = {260-263}, doi = {10.1159/000545128}, pmid = {40188806}, issn = {2504-2106}, mesh = {Humans ; Anti-Inflammatory Agents/therapeutic use ; *Phytotherapy ; *Plant Extracts/therapeutic use ; *Plants, Medicinal/chemistry ; }, abstract = {Am Beispiel des in verschiedenen lokalen Traditionen genutzten Blutwurz, auch Tormentill (Potentilla erecta L.), wird exemplarisch eine offensichtliche Kluft zwischen üblichen indikationsgetriebenen Zulassungsverfahren und der empirischen Realität sowie dem Potential vieler Heilpflanzen aufgezeigt. Für Tormentillae rhizoma ist ein breites Spektrum an Inhaltsstoffen und das mit dem Vielstoffgemisch einhergehende Wirkprofil einer u.a. vielfältig antiinflammatorisch wirkenden systemischen Droge experimentell belegt. Die traditionelle Empirie der dämpfenden Effekte im Entzündungsgeschehen wird dadurch plausibilisiert. Die moderne Forschung liefert also Daten für einen sinnvollen Einsatz einer gut verträglichen Heilpflanze mit vielfältigen Anwendungsmöglichkeiten für Haut und Schleimhaut (innerlich und äusserlich). Auf dem Markt gibt es aber, abgesehen von vereinzelten topischen Spezialitäten und Arzneitees, kaum Zubereitungen als zugelassene Arzneispezialität. Denn die derzeitige Praxis der Arzneimittelzulassung bevorzugt die spezifischen und organbezogenen Wirkungen und übersieht dabei das systemische Potential, die Modulationsfähigkeit dieser natürlichen Stoffgemische, wie sie durch traditionelle und empirische Belege angezeigt wird. Systemische Wirkungen zeigen ihre Stärke gerade im Zusammenspiel mit anderen Therapien insbesondere beim additiven Einsatz mit Spezifika, indem sie bestimmte Wirkungen verstärken bzw. abschwächen oder die Verträglichkeit der Spezifika erhöhen bzw. deren Nebenwirkungen abmildern. Die Kombination von spezifisch wirkenden Arzneimitteln mit solchen Systemmitteln (wie z.B. Blutwurz/Tormentill) stellt damit eine weitere Therapieoption dar, die als sinnvolle Ergänzung, wenn nicht sogar als Grundlage bei Prävention, Therapie und Lebensgestaltung zu werten ist. The example of tormentil (Potentilla erecta L.), which is used in various local traditions, is taken to illustrate an obvious gap between the common indication-driven authorization procedures and the empirical reality and potential of many medicinal plants. For Tormentillae rhizoma, a broad spectrum of active compounds and the active profile of a systemic drug with multiple anti-inflammatory effects have been experimentally proven. The traditional empiricism of the dampening effects in the inflammatory process is thus made plausible. Modern research, therefore, provides data for the effective use of a well-tolerated medicinal plant with a wide range of possible applications for the skin and mucous membranes (internally and externally). However, apart from a few topical specialties and medicinal teas, there are hardly any preparations on the market as authorized medicinal specialties. This is because the current practice of marketing authorization favors the specific and organ-related effects and overlooks the systemic potential, the modulation capacity of these natural substance mixtures, as indicated by traditional and empirical evidence. Systemic effects show their strength particularly in combination with other therapies, especially when used additively with specific agents, in that they strengthen or weaken certain effects or increase the tolerability of the specific agents or minimize their side effects. The combination of specific drugs with such systemic drugs (e.g., bloodroot/tormentil) therefore represents a further therapeutic option that can be seen as a valuable addition, if not a basis for prevention, therapy and lifestyle.}, } @article {pmid40188740, year = {2025}, author = {Kuo, YC and Yang, CC and Tsai, LK}, title = {Exploring CSF biomarkers in amyotrophic lateral sclerosis: Highlighting the significance of TDP-43.}, journal = {Journal of the neurological sciences}, volume = {472}, number = {}, pages = {123479}, doi = {10.1016/j.jns.2025.123479}, pmid = {40188740}, issn = {1878-5883}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/cerebrospinal fluid/blood/physiopathology/diagnosis ; Male ; Female ; *DNA-Binding Proteins/cerebrospinal fluid/blood ; Middle Aged ; Biomarkers/cerebrospinal fluid/blood ; Neurofilament Proteins/cerebrospinal fluid ; Aged ; tau Proteins/cerebrospinal fluid ; Disease Progression ; Cohort Studies ; Adult ; Severity of Illness Index ; }, abstract = {PURPOSE: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the existence of the TAR DNA-binding protein 43 (TDP-43) aggregates in motor neurons. This study investigated specific cerebrospinal fluid (CSF) biomarkers, including TDP-43, as diagnostic or prognostic biomarkers for ALS.

METHODS: The study included a hospital-based cohort of sporadic ALS patients (N = 30) and age-matched controls (N = 19). Using immunomagnetic reduction technology, CSF levels of TDP-43, neurofilament light chain (NfL), phosphorylated tau 181 (p-tau181), and total tau (t-tau) were assessed. Plasma levels of TDP-43 were also measured. The association of the different biomarkers with disease severity was investigated using ALS Functional Rating Scale-Revised (ALSFRS-R) scores, forced vital capacity (FVC), and compound muscle action potential (CMAP) amplitudes. The rate of disease progression was evaluated by measuring decline in ALSFRS-R over time.

RESULTS: ALS patients had higher CSF NfL and lower ratio of p-tau181/t-tau than control subjects. No significant difference between groups was observed in CSF TDP-43. In ALS patients, CSF levels of any biomarker, including TDP-43, were not associated with ALSFRS-R scores, FVC, or mean CMAP amplitudes. However, CSF TDP-43 positively correlated with the rate of decline in ALSFRS-R (p = 0.042). ALS patients with high CSF TDP-43 levels (>5 pg/mL) showed larger decline in ALSFRS-R (14.0 ± 11.90 vs. 8.8 ± 5.48 per year; p = 0.045) than those with lower TDP-43. Plasma TDP-43 levels did not correlate with CSF TDP-43 or any clinical parameter.

CONCLUSION: CSF TDP-43 is associated with the rate of disease progression and may be a prognostic biomarker in patients with sporadic ALS.}, } @article {pmid40188375, year = {2025}, author = {Prajapati, JL and Dhurandhar, Y and Singh, AP and Gupta, DK and Baghel, VS and Kushwaha, U and Namdeo, KP}, title = {Redox chemical delivery system: an innovative strategy for the treatment of neurodegenerative diseases.}, journal = {Expert opinion on drug delivery}, volume = {22}, number = {6}, pages = {805-822}, doi = {10.1080/17425247.2025.2489558}, pmid = {40188375}, issn = {1744-7593}, mesh = {Humans ; *Drug Delivery Systems ; *Neurodegenerative Diseases/drug therapy/physiopathology ; Oxidation-Reduction ; Blood-Brain Barrier/metabolism ; Animals ; *Central Nervous System Agents/administration & dosage/pharmacokinetics ; Brain/metabolism ; }, abstract = {INTRODUCTION: It is anticipated that the prevalence of illnesses affecting the central nervous system (CNS) will rise significantly due to longer lifespans and changing demography. Age-related decline in brain function and neuronal death are features of neurodegenerative disorders, such as Parkinson's disease, Alzheimer's disease, Huntington's disease, and amyotrophic lateral sclerosis, which provide formidable treatment challenges. Because most therapeutic drugs cannot across the blood-brain barrier (BBB) to reach the brain, there are still few treatment alternatives available despite a great deal of research.

AREAS COVERED: This study explores the role of redox chemical delivery systems in CNS drug delivery and addresses challenges associated with neurodegenerative disease (ND). Redox Chemical Delivery System offers a promising approach to enhancing leveraging redox reactions that facilitate the transport of therapeutic agents across the BBB. Through the optimization of medication delivery pathways to the brain, this technology has the potential to greatly improve the treatment of ND.

EXPERT OPINION: As our understanding of the biological underpinnings of ND deepens, the potential for effective interventions increases. Refining drug delivery strategies, such as RCDS, is essential for advancing CNS therapies from research to clinical practice. These advancements could transform the management of ND, improving both treatment efficacy and patient outcomes.}, } @article {pmid40187044, year = {2025}, author = {Fu, Y and Zhang, J and Qin, R and Ren, Y and Zhou, T and Han, B and Liu, B}, title = {Activating autophagy to eliminate toxic protein aggregates with small molecules in neurodegenerative diseases.}, journal = {Pharmacological reviews}, volume = {77}, number = {3}, pages = {100053}, doi = {10.1016/j.pharmr.2025.100053}, pmid = {40187044}, issn = {1521-0081}, mesh = {Humans ; *Autophagy/drug effects ; *Neurodegenerative Diseases/drug therapy/metabolism/pathology ; Animals ; *Protein Aggregates/drug effects ; *Protein Aggregation, Pathological/drug therapy/metabolism ; }, abstract = {Neurodegenerative diseases (NDs), such as Alzheimer disease, Parkinson disease, Huntington disease, amyotrophic lateral sclerosis, and frontotemporal dementia, are well known to pose formidable challenges for their treatment due to their intricate pathogenesis and substantial variability among patients, including differences in environmental exposures and genetic predispositions. One of the defining characteristics of NDs is widely reported to be the buildup of misfolded proteins. For example, Alzheimer disease is marked by amyloid beta and hyperphosphorylated Tau aggregates, whereas Parkinson disease exhibits α-synuclein aggregates. Amyotrophic lateral sclerosis and frontotemporal dementia exhibit TAR DNA-binding protein 43, superoxide dismutase 1, and fused-in sarcoma protein aggregates, and Huntington disease involves mutant huntingtin and polyglutamine aggregates. These misfolded proteins are the key biomarkers of NDs and also serve as potential therapeutic targets, as they can be addressed through autophagy, a process that removes excess cellular inclusions to maintain homeostasis. Various forms of autophagy, including macroautophagy, chaperone-mediated autophagy, and microautophagy, hold a promise in eliminating toxic proteins implicated in NDs. In this review, we focus on elucidating the regulatory connections between autophagy and toxic proteins in NDs, summarizing the cause of the aggregates, exploring their impact on autophagy mechanisms, and discussing how autophagy can regulate toxic protein aggregation. Moreover, we underscore the activation of autophagy as a potential therapeutic strategy across different NDs and small molecules capable of activating autophagy pathways, such as rapamycin targeting the mTOR pathway to clear α-synuclein and Sertraline targeting the AMPK/mTOR/RPS6KB1 pathway to clear Tau, to further illustrate their potential in NDs' therapeutic intervention. Together, these findings would provide new insights into current research trends and propose small-molecule drugs targeting autophagy as promising potential strategies for the future ND therapies. SIGNIFICANCE STATEMENT: This review provides an in-depth overview of the potential of activating autophagy to eliminate toxic protein aggregates in the treatment of neurodegenerative diseases. It also elucidates the fascinating interrelationships between toxic proteins and the process of autophagy of "chasing and escaping" phenomenon. Moreover, the review further discusses the progress utilizing small molecules to activate autophagy to improve the efficacy of therapies for neurodegenerative diseases by removing toxic protein aggregates.}, } @article {pmid40186067, year = {2025}, author = {Maranzano, A and Gentile, F and Passaretti, M and Doretti, A and Colombo, E and Wall, AK and Treddenti, M and Patisso, V and De Lorenzo, A and Gendarini, C and Cocuzza, A and Maio, AD and Pierro, S and Poletti, B and Cinnante, CM and Morelli, C and Messina, S and Pereira, JB and Hardiman, O and Silani, V and Verde, F and Ticozzi, N}, title = {Rate of change in upper and lower motor neuron burden is associated with survival in amyotrophic lateral sclerosis.}, journal = {Journal of neurology}, volume = {272}, number = {4}, pages = {315}, pmid = {40186067}, issn = {1432-1459}, support = {2022-12375731//Ministero della Salute/ ; E3-2022-23683266//Ministero della Salute/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/mortality/pathology/diagnosis/physiopathology ; Male ; Female ; Middle Aged ; *Motor Neurons/pathology ; Retrospective Studies ; Aged ; Disease Progression ; Adult ; Severity of Illness Index ; Cohort Studies ; ROC Curve ; }, abstract = {BACKGROUND: We hypothesize that the rate of change in upper (ΔUMN) and lower (ΔLMN) motor neuron signs from symptom onset to first clinical assessment represent best predictors of survival and disease progression in amyotrophic lateral sclerosis (ALS) compared to singular quantification of UMN and LMN involvement.

METHODS: A retrospective inpatient cohort of 1000 ALS patients was evaluated. The burden of UMN and LMN signs was assessed using the Penn Upper Motor Neuron Score and Lower Motor Neuron Score, respectively. For 421 patients, we compute the ENCALS survival model. Univariate and regularized Cox regressions were conducted to estimate the effect of the aforementioned variables on survival. The ROC curve analysis was then employed to a training sub-cohort to identify a ΔLMN cut-off value discriminating ALS patients with prolonged vs short survival. This cut-off value was then cross validated on a test sub-cohort. A multinomial regression model was used to compare different ΔUMN and ΔLMN scores among ENCALS groups.

RESULTS: ΔUMN and ΔLMN showed a negative association with survival (ΔUMN: HR = 1.30; ΔLMN: HR = 4.22). A cut-off value of 0.22 for ΔLMN was identified to predict patients with estimated short vs prolonged survival. ENCALS groups characterized by shorter survival presented significantly higher ΔUMN and ΔLMN scores compared to those with longer survival. No significant association of PUMNS or LMNS gross scores with the above-mentioned variables was observed.

CONCLUSION: By reflecting the progressing degeneration of the two distinct motor neuron subpopulations, ΔUMN and ΔLMN might represent reliable and easily measurable clinical indexes to estimate survival in ALS.}, } @article {pmid40185982, year = {2025}, author = {Cummings, JL and Teunissen, CE and Fiske, BK and Le Ber, I and Wildsmith, KR and Schöll, M and Dunn, B and Scheltens, P}, title = {Biomarker-guided decision making in clinical drug development for neurodegenerative disorders.}, journal = {Nature reviews. Drug discovery}, volume = {24}, number = {8}, pages = {589-609}, doi = {10.1038/s41573-025-01165-w}, pmid = {40185982}, issn = {1474-1784}, mesh = {Humans ; *Biomarkers/metabolism/blood ; *Drug Development/methods ; *Neurodegenerative Diseases/drug therapy/diagnosis ; Clinical Trials as Topic/methods ; Animals ; Alzheimer Disease/drug therapy ; }, abstract = {Neurodegenerative disorders are characterized by complex neurobiological changes that are reflected in biomarker alterations detectable in blood, cerebrospinal fluid (CSF) and with brain imaging. As accessible proxies for processes that are difficult to measure, biomarkers are tools that hold increasingly important roles in drug development and clinical trial decision making. In the past few years, biomarkers have been the basis for accelerated approval of new therapies for Alzheimer disease and amyotrophic lateral sclerosis as surrogate end points reasonably likely to predict clinical benefit.Blood-based biomarkers are emerging for Alzheimer disease and other neurodegenerative disorders (for example, Parkinson disease, frontotemporal dementia), and some biomarkers may be informative across multiple disease states. Collection of CSF provides access to biomarkers not available in plasma, including markers of synaptic dysfunction and neuroinflammation. Molecular imaging is identifying an increasing array of targets, including amyloid plaques, neurofibrillary tangles, inflammation, mitochondrial dysfunction and synaptic density. In this Review, we consider how biomarkers can be implemented in clinical trials depending on their context of use, including providing information on disease risk and/or susceptibility, diagnosis, prognosis, pharmacodynamic outcomes, monitoring, prediction of response to therapy and safety. Informed choice of increasingly available biomarkers and rational deployment in clinical trials support drug development decision making and de-risk the drug development process for neurodegenerative disorders.}, } @article {pmid40185700, year = {2025}, author = {Yang, T and Pang, D and Huang, J and Xiao, Y and Li, C and Wei, Q and Ou, R and Cheng, Y and Lin, J and Che, N and Fu, J and Jiang, Q and Wang, S and Liu, J and Zhang, S and Shang, H}, title = {Association between sleep and ALS-FTSD: A Prospective Cohort Study based on 396,918 UK biobank participants.}, journal = {Translational psychiatry}, volume = {15}, number = {1}, pages = {123}, pmid = {40185700}, issn = {2158-3188}, support = {82371430//National Natural Science Foundation of China (National Science Foundation of China)/ ; }, mesh = {Humans ; Male ; Female ; Middle Aged ; United Kingdom/epidemiology ; Prospective Studies ; *Amyotrophic Lateral Sclerosis/epidemiology ; *Sleep Wake Disorders/epidemiology/complications ; Aged ; Risk Factors ; Biological Specimen Banks ; *Sleep/physiology ; Incidence ; Adult ; Proportional Hazards Models ; *Frontotemporal Dementia/epidemiology ; UK Biobank ; }, abstract = {Amyotrophic lateral sclerosis-frontotemporal spectrum disorder (ALS-FTSD) is a fatal neurodegenerative condition, and identifying its modifiable risk factors is a critical public health issue. This large-scale prospective cohort study investigated the role of sleep-related factors in ALS-FTSD risk using data from 396,918 UK Biobank participants. Eight sleep-related exposures were assessed, and Cox proportional hazards regression was employed to evaluate their associations with ALS-FTSD incidence. Subgroup and sensitivity analyses were conducted to validate the robustness of our findings. At baseline, participants had a mean age of 56.31 ± 8.12 years, with 47.5% being male. In the fully adjusted Cox model, organic sleep disorders (G47) (HR: 1.81, 95% CI: 1.21, 2.72, P = 0.004), hypersomnia (G47.1) (HR: 36.53, 95% CI: 9.04, 147.55, P < 0.001), and extreme short sleep (<5 h per day) (HR: 2.09, 95% CI: 1.09, 3.99, P = 0.046) were significantly associated with increased ALS-FTSD risk. In conclusions, these findings revealed the relationship between sleep and the risk of ALS-FTSD, identifying new modifiable risk factors and potential preventive possibilities for ALS-FTSD. Further research is warranted to elucidate the mechanistic links between sleep disturbances and ALS-FTSD pathogenesis.}, } @article {pmid40185615, year = {2025}, author = {Dawson, M}, title = {Marxism on Musk: reflections on Baum et al's 'Twenty-First Century Alienation and Health'.}, journal = {Journal of epidemiology and community health}, volume = {79}, number = {7}, pages = {477-478}, doi = {10.1136/jech-2025-223762}, pmid = {40185615}, issn = {1470-2738}, } @article {pmid40185536, year = {2025}, author = {Uzgiris, AJ and Ladic, LA and Pfister, SX}, title = {Advances in neurofilament light chain analysis.}, journal = {Advances in clinical chemistry}, volume = {126}, number = {}, pages = {31-71}, doi = {10.1016/bs.acc.2025.01.006}, pmid = {40185536}, issn = {2162-9471}, mesh = {*Neurofilament Proteins/analysis ; Humans ; Biomarkers/analysis ; *Nervous System Diseases/diagnosis/metabolism ; }, abstract = {This chapter provides a comprehensive summary of clinical laboratory testing for neurofilament light chain (NfL) in neurologic disease. A primer on the NfL structure and function is presented with its potential use as a biomarker. The most widely utilized methods for NfL in biologic samples are highlighted and examined. Limitations of current knowledge are considered, as are outstanding questions related to dissemination and standardization of testing. Herein we focus on methods available today and those in development for clinical use. In the final section, a broad vision is presented of how NfL may be utilized in the future to improve diagnosis and treatment of neurologic diseases as well as for maintaining health.}, } @article {pmid40185386, year = {2025}, author = {Lei, S and Liu, Y}, title = {Identifying blood mitochondrial DNA copy number as a biomarker for development of neurodegenerative diseases: Evidence from Mendelian randomization analysis.}, journal = {Neuroscience}, volume = {573}, number = {}, pages = {421-429}, doi = {10.1016/j.neuroscience.2025.04.003}, pmid = {40185386}, issn = {1873-7544}, mesh = {Humans ; *DNA, Mitochondrial/blood/genetics ; Mendelian Randomization Analysis ; *Neurodegenerative Diseases/genetics/blood ; *DNA Copy Number Variations/genetics ; Genome-Wide Association Study ; Biomarkers/blood ; }, abstract = {Mitochondrial dysfunction has been associated with neurodegenerative diseases (NDDs). This study aimed to explore the association between blood mitochondrial DNA copy number (mtDNA-CN) and development of NDDs. This study was based on two-sample Mendelian randomization (MR) analysis. The genome wide association study (GWAS) data of NDDs including Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), age-related macular degeneration (AMD), multiple sclerosis (MS), Parkinson's disease (PD), primary open-angle glaucoma (POAG), and vascular dementia (VD) was obtained from FinnGen consortium. Inverse-variance weighted (IVW) was applied as the primary approach for MR estimation. MR results revealed that blood mtDNA-CN exhibited a significant relationship with the incidence of AD (IVW-P = 0.011, odds ratio [OR] = 0.65) and AMD (IVW-P = 0.038, OR = 0.64). However, there was no significant association observed between blood mtDNA-CN and other NDDs (IVW-P > 0.05). Our findings supported the relationship between mitochondrial dysfunction and development of AD and AMD, and that blood mtDNA-CN may serve as a potential biomarker for the incidence of these two NDDs.}, } @article {pmid40185066, year = {2025}, author = {Fujii, T and Honda, H and Yoshidomi, S and Kashu, KY and Yamasaki, R and Yoshimura, M and Sasagasako, N and Iwaki, T and Isobe, N}, title = {Plexin D1 accumulation in the spinal motor neurons of patients with amyotrophic lateral sclerosis.}, journal = {Journal of the neurological sciences}, volume = {472}, number = {}, pages = {123483}, doi = {10.1016/j.jns.2025.123483}, pmid = {40185066}, issn = {1878-5883}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/pathology/metabolism ; Male ; Female ; Middle Aged ; *Motor Neurons/metabolism/pathology ; *Spinal Cord/metabolism/pathology ; Aged ; *Nerve Tissue Proteins/metabolism ; DNA-Binding Proteins/metabolism ; Endothelial Cells/metabolism ; Adult ; }, abstract = {BACKGROUND: Plexin D1 in endothelial cells (ECs) in the spinal cord (SC) has emerged as a key protein in spinal motor neuron (MN) maturation. Here, we pathologically investigated plexin D1 expression in the SCs of patients with sporadic amyotrophic lateral sclerosis (sALS) to clarify the association between plexin D1 expression in ECs and MN degeneration.

METHODS: We measured plexin D1 expression in the ECs of lumbar SC tissue samples from 11 patients with sALS and 8 age- and sex-matched patients with other non-inflammatory neurological diseases (OND) by immunohistochemistry. Additionally, the number and percentage of plexin D1-positive MNs in lumbar MNs were assessed in each case. We also evaluated the immunoreactivity of TAR DNA binding protein (TARDBP) in plexin D1-positive MNs.

RESULTS: Immunohistochemistry showed that there was no obvious difference in plexin D1 expression in ECs between sALS and OND cases. Unexpectedly, plexin D1 accumulation was greater in MNs of patients with sALS compared with those with OND. The number and percentage of plexin D1-positive MNs in patients with sALS were significantly greater than in patients with OND (median [interquartile range], 6 [1-11] vs. 1 [0-3.3], p = 0.0349; and 12.9 % [5.5-15.5] vs. 1.1 % [0-3.5], p = 0.0032, respectively). Plexin D1-positive MNs showed TARDBP cytoplasmic mislocalization and aggregation.

CONCLUSIONS: Plexin D1 was similarly expressed in ECs between sALS and OND cases, but accumulated in the degenerated MNs of patients with sALS. Plexin D1 accumulation in MNs may provide new insights into the mechanism of MN degeneration in ALS.}, } @article {pmid40184864, year = {2025}, author = {Deloncle, R and Guillard, O and Pineau, A}, title = {Copper in human health: From COVID 19 to neurodegenerative diseases.}, journal = {Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS)}, volume = {89}, number = {}, pages = {127636}, doi = {10.1016/j.jtemb.2025.127636}, pmid = {40184864}, issn = {1878-3252}, mesh = {*Copper/metabolism ; Humans ; *Neurodegenerative Diseases/metabolism ; *COVID-19/metabolism ; Animals ; SARS-CoV-2 ; Brain/metabolism ; }, abstract = {Copper (Cu) exists in two oxidation states Cu+I and Cu+II yielding formation of enzymes involved in biological processes. In higher concentrations, by oxidative process and ROS production, Cu is toxic towards plants, humans and animals livers as observed in Wilson disease or sheep scrapie. Fighting according to the Fenton reaction against bacteria and viruses, has been proposed as a mean of combatting nosocomial diseases and complementary to COVID19 vaccination. In humans, Cu is stocked in liver, muscle or bound to brain protein as ß-APP, tau-protein, α-synuclein, ubiquitin or prion which present antioxidant properties when Cu-bonded. In abnormal ß-sheet conformation, they can trigger neurodegenerative diseases such as Alzheimer(AD), Parkinson(PD) and ALS. In these diseases, blood copper increase correlated with brain copper decrease has been described. In AD, abnormal D-serine has been detected in blood and cerebrospinal fluid. D-glutamate and D-alanine blood levels have been found in AD and could also be controlled with Cu and ceruloplasmin in a possible disease screening test. This abnormal D-conformation might result from epimerization of physiologically L-conformation brain peptides into protease-resistant D-enantiomers. This has previously been experimentally demonstrated for Bovine Spongiform Encephalopathy in a free Cu reductive medium with UV-induced free radicals. The Cu brain protective effect against free radicals was restored with cupric addition in oxidizing medium. Cupric supplementation in the brain, might restore Cu protection and slow down neurodegenerative processes. To lower side effects, Cu amino-acid complexes able to cross the blood brain barrier might be suggested for a Cu transfer to the brain.}, } @article {pmid40184012, year = {2025}, author = {Chowdhury, MR and Reddy, RVS and Nampoothiri, NK and Erva, RR and Vijaykumar, SD}, title = {Exploring bioactive natural products for treating neurodegenerative diseases: a computational network medicine approach targeting the estrogen signaling pathway in amyotrophic lateral sclerosis and Parkinson's disease.}, journal = {Metabolic brain disease}, volume = {40}, number = {4}, pages = {169}, doi = {10.1007/s11011-025-01585-y}, pmid = {40184012}, issn = {1573-7365}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy/metabolism/genetics ; *Parkinson Disease/drug therapy/metabolism/genetics ; *Signal Transduction/drug effects/physiology ; Computational Biology/methods ; *Estrogens/metabolism ; *Biological Products/therapeutic use/pharmacology ; Protein Interaction Maps/drug effects ; Neuroprotective Agents/pharmacology/therapeutic use ; Gene Regulatory Networks/drug effects ; }, abstract = {Amyotrophic lateral sclerosis (ALS) and Parkinson's disease (PD) share overlapping molecular mechanisms, including estrogen signaling dysregulation, oxidative stress, and neuroinflammation. Standard treatments often lead to adverse effects due to unintended cross-talk with the estrogen signaling pathway. Identifying key regulatory genes and bioactive plant-derived compounds that modulate estrogen signaling without interfering with standard therapies offers a promising neuroprotective strategy. A network medicine and systems biology approach was used, beginning with the screening of 29 medicinal plants for ALS and 49 for PD, identifying 12 shared plants with neuroprotective potential. Bioactive compounds were screened for gene, protein, and pathway interactions, leading to target prediction (846 ALS-related and 690 PD-related targets) and disease association mining, which identified 93 overlapping genes (OGs). Protein-protein interaction (PPI) network analysis and MCODE clustering revealed ESR1, EGFR, and SRC as key hub-bottleneck (HB) genes, further validated via differential gene expression analysis. Gene ontology (GO) and pathway enrichment analyses revealed significant enrichment in estrogen signaling confirming the involvement of HB genes in neurodegenerative disease progression. Differential expression analysis confirmed ESR1 upregulation in ALS but downregulation in PD, suggesting a converse disease-specific regulatory pattern. Gene regulatory network (GRN) analysis identified hsa-miR-145-5p (ALS) and hsa-miR-181a-5p (PD) as key regulators, while FOXC1, GATA2, and TP53 emerged as crucial transcription factors (TFs) influencing disease progression. Molecular docking and MD simulations validated strong and stable interactions of Eupalitin (CYP19A1, -9.0 kcal/mol), Hesperetin (ESR1, -8.1 kcal/mol), and Sumatrol (PIK3CA, -8.9 kcal/mol). These phytochemicals, derived from Rosmarinus officinalis, Artemisia scoparia, Ocimum tenuiflorum, and Indigofera tinctoria, maintained stable hydrogen bonding and hydrophobic interactions for over 30% of a 25 ns simulation, supporting their therapeutic potential. The identification of ESR1, EGFR, and SRC as key targets, alongside estrogen signaling involvement, highlights the need for targeted nutraceutical interventions. These findings pave the way for safer, plant-based therapies that mitigate neurodegeneration while preserving estrogen signaling integrity, offering a promising adjuvant strategy alongside existing treatments.}, } @article {pmid40183526, year = {2025}, author = {Dorst, J and Dreyhaupt, J and Wernecke, D and Weiland, U and Parlak, Ö and Wiesenfarth, M and Elmas, Z and Herrmann, C and Bäzner, H and Boertlein, A and Dempewolf, S and Foerch, C and Hecht, M and Kohler, A and Opherk, C and Althaus, K and Clauer-Bredt, M and Lindner, A and Ruf, W and Brenner, D and Witzel, S and Peter, RS and Schuster, J and Ludolph, AC and Rosenbohm, A and Nagel, G}, title = {Population-Based Versus Hospital-Based Data in Amyotrophic Lateral Sclerosis-A Factor to Consider?.}, journal = {European journal of neurology}, volume = {32}, number = {4}, pages = {e70137}, pmid = {40183526}, issn = {1468-1331}, support = {577631//Deutsche Forschungsgemeinschaft/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/epidemiology/diagnosis/therapy ; Male ; Female ; Middle Aged ; Aged ; *Registries ; Selection Bias ; *Hospitals/statistics & numerical data ; }, abstract = {BACKGROUND: Over the past years, some studies in amyotrophic lateral sclerosis (ALS) have provided heterogeneous findings regarding demographic and clinical data as well as the impact of various prognostic factors. It is well known that these inconsistencies might be caused by a selection bias in hospital-based data sets. In this study, we sought to further characterize this selection bias.

METHODS: We compared hospital-based data from the ALS center at Ulm University (UC; n = 3833; 1997-2021) with the population-based ALS registry Swabia (SR; n = 852; 2010-2020).

RESULTS: Patients from UC were younger (age of onset 60.9 [IQR 52.4-68.9] vs. 65.0 [57.0-72.7]), had a higher share of males (60.5% vs. 56.3%), a longer diagnostic delay (10.5 [IQR 6.4-18.4] months vs. 6.9 [IQR 3.4-12.1] months), a higher prevalence of the "definite" category according to El Escorial diagnostic criteria (60.9% vs. 11.2%), a higher share of familial cases (12.9% vs. 6.3%), a slower progression rate (points of ALS functional rating scale revised lost per month -0.54 [IQR -1.02 to -0.28] vs. -0.79 [IQR -1.47 to -0.43]), and (among all deceased patients) a higher share of percutaneous endoscopic gastrostomy (26.7% vs. 17.7%) and non-invasive ventilation (34.3% vs. 25.3%).

CONCLUSIONS: The observed differences likely indicate a selection bias in hospital-based data, which may be attributed, among others, to the willingness to travel large distances to a specialized center, the desire to participate in clinical studies, and the attitude toward life-prolonging measures. These differences must be considered when interpreting and generalizing study results from hospital-based populations.}, } @article {pmid40183433, year = {2025}, author = {Jiang, J and Li, X and Mi, Y and Wang, Y and Heng, Y and Li, Z and Deng, M}, title = {Real-world evidence of riluzole on survival and ALSFRS change in a Chinese ALS cohort.}, journal = {Neurodegenerative disease management}, volume = {15}, number = {2-3}, pages = {77-87}, pmid = {40183433}, issn = {1758-2032}, mesh = {Humans ; *Riluzole/therapeutic use ; *Amyotrophic Lateral Sclerosis/drug therapy/mortality ; Female ; Male ; Middle Aged ; *Neuroprotective Agents/therapeutic use ; Aged ; China ; Adult ; Cohort Studies ; Kaplan-Meier Estimate ; Treatment Outcome ; East Asian People ; }, abstract = {AIMS: This study aimed to evaluate the effects of riluzole on survival and changes in ALS Functional Rating Scale (ALSFRS) among Chinese patients with Amyotrophic Lateral Sclerosis (ALS).

PATIENTS & METHODS: Propensity score matching was used to balance baseline variables between the riluzole group (n = 238) and control group (n = 454). Survival was analyzed using Kaplan - Meier curves and Cox regression, while multivariable linear regression assessed ALSFRS changes at 6 and 12 months. Subgroup analyses were conducted to identify potential responders.

RESULTS: Riluzole did not significantly improve survival (p = 0.478) or ALSFRS changes at 6 months (p = 0.380) or 12 months (p = 0.175). Subgroup analyses revealed no survival benefit in any subgroup, and further stratification showed inconsistent adverse effects on ALSFRS scores.

CONCLUSIONS: Riluzole neither prolonged survival nor slowed functional decline in Chinese ALS patients, with no subgroup demonstrating a better response.}, } @article {pmid40183173, year = {2025}, author = {Zulueta, A and Piras, R and Azzolino, D and Mariani, P and Sideri, R and Garrè, C and Federico, G and Lucchi, T and Magni, P and Parati, EA and Lunetta, C}, title = {Neurofilament Light Chain Levels, Skeletal Muscle Loss, and Nutritional Decline: Key Prognostic Factors in Amyotrophic Lateral Sclerosis.}, journal = {Muscle & nerve}, volume = {72}, number = {1}, pages = {49-55}, pmid = {40183173}, issn = {1097-4598}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/complications/diagnosis/metabolism/blood ; Male ; Female ; Middle Aged ; Aged ; *Neurofilament Proteins/metabolism/blood ; Disease Progression ; *Malnutrition/diagnosis/etiology ; Prognosis ; *Nutritional Status/physiology ; *Muscle, Skeletal/metabolism/pathology ; Body Composition/physiology ; Adult ; Body Mass Index ; }, abstract = {INTRODUCTION/AIMS: Hypermetabolism and weight loss are established negative prognostic factors in amyotrophic lateral sclerosis (ALS). However, the role of individualized body composition parameters in predicting ALS progression has been underexplored. This study aimed to investigate the correlation between nutritional parameters, neurofilament light chain (NfL) levels, and disease progression in ALS patients.

METHODS: The Global Leadership Initiative on Malnutrition criteria were used to define malnutrition in this study. Nutritional status was assessed using body mass index and bioelectrical impedance analysis. The rate of disease progression was defined by the change in the Revised ALS Functional Rating Scale score (ΔFRS). NfL was quantified using single molecule array technology. Spearman's analyses were used to assess correlations.

RESULTS: Sixty of 110 ALS patients were classified as malnourished. There was a strong positive correlation between NfL and ΔFRS (r = 0.71), and a moderate negative correlation with disease duration (r = -0.55). The correlations between NfL and body composition parameters were statistically significant, although weak. NfL levels were significantly higher in fast progressors (p < 0.0001 compared to slow progressors) and in malnourished patients (p = 0.0001). Of the 34 fast progressor patients, 28 (82%) exhibited some degree of malnutrition.

DISCUSSION: Our findings indicate that poor nutritional status, particularly reduced skeletal muscle mass-both independently and in combination with fat mass loss-is associated with elevated NfL levels and faster ALS progression. NfL, combined with nutritional parameters, could serve as a valuable biomarker for disease severity. Further research is warranted to clarify the role of skeletal muscle abnormalities in ALS progression.}, } @article {pmid40182859, year = {2025}, author = {Kobayakawa, Y and Ko, S and Tashiro, T and Maimaitijiang, G and Kira, JI and Kishimoto, J and Yamasaki, R and Isobe, N}, title = {FVC-DiP correlates with neurofilament light chain levels in serum and cerebrospinal fluid in patients with ALS.}, journal = {BMJ neurology open}, volume = {7}, number = {1}, pages = {e001012}, pmid = {40182859}, issn = {2632-6140}, abstract = {BACKGROUND: We previously reported a scale to assess the disease progression rate in patients with amyotrophic lateral sclerosis (ALS), the forced vital capacity decline pattern scale (FVC-DiP). In this study, we investigated the association between FVC-DiP scores and neurofilament light chain (NfL) in the serum and cerebrospinal fluid (CSF) in patients with ALS.

METHODS: We performed a retrospective study to examine the association between NfL levels and the rate of disease progression (N=41). The disease progression rate was assessed using three methods: the FVC-DiP score determined using the percentage of predicted FVC (%FVC) and disease duration at the %FVC measurement, the rate of decline in the ALS Functional Rating Scale Revised (ALSFRS-R) score (ΔFS) and the rate of decline in the %FVC (Δ%FVC).

RESULTS: The FVC-DiP scores were significantly correlated with NfL levels in both the serum and CSF (serum, R[2]=0.274, p<0.001; CSF, R[2]=0.274, p=0.001). Patients assessed as rapidly progressing by the FVC-DiP had high NfL levels, and patients assessed as slowly progressing had low NfL levels. In the group with a low ΔFS and/or Δ%FVC, although the disease progression rate assessed by the FVC-DiP may have differed from the assessments obtained using the ALSFRS-R and/or %FVC, the correlation between FVC-DiP scores and serum NfL levels remained consistent.

CONCLUSIONS: The FVC-DiP was significantly associated with NfL levels in the serum and CSF, suggesting that the FVC-DiP is a reasonable scale to assess the rate of ALS progression.}, } @article {pmid40181571, year = {2025}, author = {Yoganathan, K and Dharmadasa, T and Northall, A and Talbot, K and Thompson, AG and Turner, MR}, title = {Asymmetry in amyotrophic lateral sclerosis: Clinical, neuroimaging and histological observations.}, journal = {Brain : a journal of neurology}, volume = {148}, number = {8}, pages = {2605-2615}, pmid = {40181571}, issn = {1460-2156}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/pathology/physiopathology/diagnostic imaging ; *Neuroimaging/methods ; *Brain/pathology/diagnostic imaging ; Disease Progression ; Spinal Cord/pathology/diagnostic imaging ; *Functional Laterality/physiology ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease of the motor system marked by significant phenotypic heterogeneity. Motor symptoms in the limbs consistently emerge focally and asymmetrically and, whilst variable, the pattern of regional progression related to the balance of clinical upper and lower motor neuron signs, upper versus lower limb onset and hand dominance to some extent. The neurobiological mechanisms and pathological correlates for this lateralized onset and non-random progression are uncertain. Cerebral neuroimaging studies have commonly reported structural and functional asymmetries in ALS, but the limited analysis of the pre-symptomatic phase has limited their implications. Post-mortem study of spinal cord provided strong evidence for focal pathology at symptom onset in ALS. Histopathological staging of molecular pathology in post-mortem tissue lacks clinical correlation and an ordered, sequential temporal progression in life cannot be assumed. The development of integrated brain and cord MRI holds the hope of deepening understanding of the relationship between focal symptomatology and histopathological progression. This review considers the nature and implications of asymmetry in ALS across clinical, neuroimaging and post-mortem histopathology, highlighting the current gaps in knowledge and the need for a broader investigative framework.}, } @article {pmid40181198, year = {2025}, author = {Manolopoulos, A and Yao, PJ and Kapogiannis, D}, title = {Extracellular vesicles: translational research and applications in neurology.}, journal = {Nature reviews. Neurology}, volume = {21}, number = {5}, pages = {265-282}, pmid = {40181198}, issn = {1759-4766}, mesh = {Humans ; *Extracellular Vesicles/metabolism ; *Translational Research, Biomedical/methods ; Biomarkers/metabolism ; *Nervous System Diseases/therapy/diagnosis/metabolism ; Animals ; *Neurology/methods/trends ; }, abstract = {Over the past few decades, extensive basic, translational and clinical research has been devoted to deciphering the physiological and pathogenic roles of extracellular vesicles (EVs) in the nervous system. The presence of brain cell-derived EVs in the blood, carrying diverse cargoes, has enabled the development of predictive, diagnostic, prognostic, disease-monitoring and treatment-response biomarkers for various neurological disorders. In this Review, we consider how EV biomarkers can bring us closer to understanding the complex pathogenesis of neurological disorders such as Alzheimer disease, Parkinson disease, stroke, traumatic brain injury, amyotrophic lateral sclerosis and multiple sclerosis. We describe how translational research on EVs might unfold bidirectionally, proceeding from basic to clinical studies but also in the opposite direction, with biomarker findings in the clinic leading to novel hypotheses that can be tested in the laboratory. We demonstrate the potential value of EVs across all stages of the therapeutic development pipeline, from identifying therapeutic targets to the use of EVs as reporters in model systems and biomarkers in clinical research. Finally, we discuss how the cargo and physicochemical properties of naturally occurring and custom-engineered EVs can be leveraged as novel treatments and vehicles for drug delivery, potentially revolutionizing neurotherapeutics.}, } @article {pmid40180875, year = {2025}, author = {Li, H and Cheng, M and Zhang, N and Wang, S and Ye, C and Li, H and Wang, S and Wang, Z and Yang, X and Liu, Z and Zhang, X and Xu, J and Xu, Q and Wang, J}, title = {The role of serum vitamins in mediating the effect of neurodegenerative diseases on subcortical brain volume.}, journal = {The journal of prevention of Alzheimer's disease}, volume = {12}, number = {6}, pages = {100155}, doi = {10.1016/j.tjpad.2025.100155}, pmid = {40180875}, issn = {2426-0266}, mesh = {Humans ; Animals ; *Neurodegenerative Diseases/pathology/blood/genetics ; *Brain/pathology ; *Vitamins/blood ; Atrophy/pathology ; Genome-Wide Association Study ; Mice ; Mendelian Randomization Analysis ; Alzheimer Disease/pathology/blood/genetics ; *Vitamin D/blood ; Male ; Hippocampus/pathology ; Parkinson Disease/pathology/blood ; }, abstract = {BACKGROUND: Neurodegenerative diseases (NDs) lead to a progressive loss of neuronal cells and link to atrophy of subcortical brain structures, but the causal intermediates are not known. To test whether major NDs (Alzheimer's disease (AD), Parkinson's disease, multiple sclerosis, and amyotrophic lateral sclerosis) causally affects subcortical atrophy, and whether serum vitamin level play a mediating role in this process.

METHODS: Using large-scale genome-wide association study (GWAS) summary data, we performed two-sample Mendelian randomization (MR) to assess the causal effect of NDs on the volume of seven subcortical structures, and then adopted two-step multivariable MR approach to quantify the proportion of the effect of NDs on the volume of subcortical regions mediated by serum vitamin level. Finally, we utilized animal experiments to validate results and explored the potential molecular mechanisms.

RESULTS: Genetically predicted AD was associated with atrophy of the nucleus accumbens (NAc) (β = -0.09; p = 5.13 × 10[-5]), amygdala (β = -0.07; p = 8.44 × 10[-4]), and hippocampus (β = -0.07; p = 0.001), as well as with low serum vitamin D level (β = -0.02; p = 6.84 × 10[-6]). Specifically, decreased serum vitamin D level mediated 3.99 % (95 % CI: -0.006 to -5.82 × 10[-5]) and 3.97 % (95 % CI: -0.007 to -2.94 × 10[-4]) of the total effect of AD on hippocampal and NAc atrophy, respectively. Animal experiments further confirmed significant delays in hippocampal and NAc atrophy, a significant reduction of β-amyloid deposits and an increase of vitamin D receptor expression in hippocampus in AD mice with high-dose vitamin D diet.

CONCLUSIONS: These findings provide important insights into the effect sizes of vitamin D-mediated roles in AD and atrophy of subcortical structures. Interventions to increase serum vitamin D levels at a population level might attenuate damage to hippocampus in patients with AD.}, } @article {pmid40180687, year = {2025}, author = {Ms, S and Banerjee, S and D'Mello, SR and Dastidar, SG}, title = {Amyotrophic Lateral Sclerosis: Focus on Cytoplasmic Trafficking and Proteostasis.}, journal = {Molecular neurobiology}, volume = {62}, number = {8}, pages = {10091-10117}, pmid = {40180687}, issn = {1559-1182}, support = {SAN No: 102/IFD/SAN/2549/2019-20//DBT RLS/ ; CRG/2022/005004//Science and Engineering Research Board/ ; LBRN//Louisiana Biomedical Research Network/ ; IIRPIG-2023-0001508//Indian Council of Medical Research/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/metabolism/pathology ; Humans ; *Proteostasis/physiology ; Animals ; *Cytoplasm/metabolism ; Endoplasmic Reticulum Stress ; Endoplasmic Reticulum/metabolism ; Golgi Apparatus/metabolism ; Protein Transport/physiology ; Motor Neurons/metabolism/pathology ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive and fatal motor neuron disease characterized by the pathological loss of upper and lower motor neurons. Whereas most ALS cases are caused by a combination of environmental factors and genetic susceptibility, in a relatively small proportion of cases, the disorder results from mutations in genes that are inherited. Defects in several different cellular mechanisms and processes contribute to the selective loss of motor neurons (MNs) in ALS. Prominent among these is the accumulation of aggregates of misfolded proteins or peptides which are toxic to motor neurons. These accumulating aggregates stress the ability of the endoplasmic reticulum (ER) to function normally, cause defects in the transport of proteins between the ER and Golgi, and impair the transport of RNA, proteins, and organelles, such as mitochondria, within axons and dendrites, all of which contribute to the degeneration of MNs. Although dysfunction of a variety of cellular processes combines towards the pathogenesis of ALS, in this review, we focus on recent advances concerning the involvement of defective ER stress, vesicular transport between the ER and Golgi, and axonal transport.}, } @article {pmid40180646, year = {2025}, author = {Temiz, K and Gul, A and Gov, E}, title = {5-Repurposed Drug Candidates Identified in Motor Neurons and Muscle Tissues with Amyotrophic Lateral Sclerosis by Network Biology and Machine Learning Based on Gene Expression.}, journal = {Neuromolecular medicine}, volume = {27}, number = {1}, pages = {24}, pmid = {40180646}, issn = {1559-1174}, mesh = {*Amyotrophic Lateral Sclerosis/drug therapy/genetics ; Humans ; *Machine Learning ; *Motor Neurons/metabolism/drug effects ; *Drug Repositioning/methods ; Transcriptome ; Gene Expression Profiling ; *Muscle, Skeletal/metabolism ; Gene Regulatory Networks ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder that leads to motor neuron degeneration, muscle weakness, and respiratory failure. Despite ongoing research, effective treatments for ALS are limited. This study aimed to apply network biology and machine learning (ML) techniques to identify novel repurposed drug candidates for ALS. In this study, we conducted a meta-analysis using 4 transcriptome data in ALS patients (including motor neuron and muscle tissue) and healthy controls. Through this analysis, we uncovered common shared differentially expressed genes (DEGs) separately for motor neurons and muscle tissue. Using common DEGs as proxies, we identified two distinct clusters of highly clustered differential co-expressed cluster genes: the 'Muscle Tissue Cluster' for muscle tissue and the 'Motor Neuron Cluster' for motor neurons. We then evaluated the performance of the nodes of these two modules to distinguish between diseased and healthy states with ML algorithms: KNN, SVM, and Random Forest. Furthermore, we performed drug repurposing analysis and text-mining analyses, employing the nodes of clusters as drug targets to identify novel drug candidates for ALS. The potential impact of the drug candidates on the expression of cluster genes was predicted using linear regression, SVR, Random Forest, Gradient Boosting, and neural network algorithms. As a result, we identified five novel drug candidates for the treatment of ALS: Nilotinib, Trovafloxacin, Apratoxin A, Carboplatin, and Clinafloxacin. These findings highlight the potential of drug repurposing in ALS treatment and suggest that further validation through experimental studies could lead to new therapeutic avenues.}, } @article {pmid40180127, year = {2025}, author = {Kaltchenko, M and Kim, E and Radtke, S and Wan, J}, title = {Response to Li et al's "Comments on 'Dupilumab and neuropsychiatric outcomes in pediatric atopic dermatitis: A real-world cohort analysis'".}, journal = {Journal of the American Academy of Dermatology}, volume = {93}, number = {1}, pages = {e41-e43}, doi = {10.1016/j.jaad.2025.03.081}, pmid = {40180127}, issn = {1097-6787}, } @article {pmid40179811, year = {2025}, author = {Li, B and Mu, H and Shan, D and Yang, Y and Wang, Y and Li, J and Wang, H and Sun, X and Ji, X and Zhan, Z and Jiao, Y and Tang, Y and Kong, B and Gao, B and Wang, Y and Sun, P and Liu, F}, title = {Generation of an induced pluripotent stem cell (iPSC) line (INNDSUi009-A) from a patient with amyotrophic lateral sclerosis due to SOD1 mutation.}, journal = {Stem cell research}, volume = {85}, number = {}, pages = {103704}, doi = {10.1016/j.scr.2025.103704}, pmid = {40179811}, issn = {1876-7753}, mesh = {Humans ; *Induced Pluripotent Stem Cells/metabolism/cytology/pathology ; *Amyotrophic Lateral Sclerosis/genetics/pathology/metabolism ; *Superoxide Dismutase-1/genetics ; *Mutation ; Cell Differentiation ; Cell Line ; Fibroblasts/metabolism/cytology ; Male ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurological disorder characterized by progressive degeneration of nerve cells in the spinal cord and brain. We generated and characterized a human induced pluripotent stem cell (iPSC) line from skin fibroblasts of a patient with ALS due to SOD1 Mutation. The pluripotency of these iPSCs was verified by the expression of several pluripotency markers at both RNA and protein levels, as well as their capability to differentiate into all three germ layers.}, } @article {pmid40179249, year = {2025}, author = {Traynor, BJ}, title = {The interneuron hypothesis of amyotrophic lateral sclerosis.}, journal = {Brain : a journal of neurology}, volume = {148}, number = {4}, pages = {1045-1046}, pmid = {40179249}, issn = {1460-2156}, support = {/NH/NIH HHS/United States ; 1ZIAAG000933/AG/NIA NIH HHS/United States ; }, } @article {pmid40178484, year = {2025}, author = {Gao, Y and Lu, Y and Chen, R and Zhao, S and Liu, J and Zhang, S and Bai, X and Zhang, J}, title = {Skin pathology in ALS: Diagnostic implications and biomarker potential.}, journal = {Biomolecules & biomedicine}, volume = {}, number = {}, pages = {}, doi = {10.17305/bb.2025.12100}, pmid = {40178484}, issn = {2831-090X}, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the loss of motor neurons in the spinal cord and brain, resulting in motor deficits and muscle atrophy. Approximately 5-10% of ALS patients are familial (fALS), while the rest are sporadic (sALS). Currently, early diagnosis of ALS cannot be achieved based on clinical manifestations and electromyography due to the lack of effective and easily available biomarkers. The skin and central nervous system (CNS) share the same embryonic origin. Several skin biomarkers have been found in many neurodegenerative diseases, such as abnormal deposition of pathological α-synuclein (α-Syn) in Parkinson's disease. Thus, molecular changes in the skin associated with ALS-specific pathological events could readily be detected and become biomarkers for ALS through skin testing. Here, we summarize the literature on pathological changes in the skin of ALS patients and animal models, including structural abnormalities of the skin, reduced density of skin nerve fibers, abnormal protein aggregation, altered mitochondrial morphology and function, and dysregulation of skin inflammation, which may be useful for early diagnosis and monitoring of ALS progression.}, } @article {pmid40178078, year = {2025}, author = {Castro, J and de Carvalho, M}, title = {Letter on "Synaptic dynamics linked to widespread elevation of H-reflex before peripheral denervation in amyotrophic lateral sclerosis".}, journal = {Journal of neurophysiology}, volume = {133}, number = {4}, pages = {1146-1147}, doi = {10.1152/jn.00582.2024}, pmid = {40178078}, issn = {1522-1598}, } @article {pmid40177728, year = {2025}, author = {Liu, S and Lun, J and Zhan, Y and Li, Z and Tian, J and Zhang, C and Pan, L}, title = {CRISPR/Cas12a Combined with RAA for On-Site Detection of ALS W574L Mutation in Three Alopecurus Species: A Visual Approach for Herbicide Resistance Monitoring.}, journal = {Journal of agricultural and food chemistry}, volume = {73}, number = {15}, pages = {8907-8914}, doi = {10.1021/acs.jafc.5c02188}, pmid = {40177728}, issn = {1520-5118}, mesh = {*Herbicide Resistance ; CRISPR-Cas Systems ; *Acetolactate Synthase/genetics/metabolism ; *Herbicides/pharmacology ; *Plant Proteins/genetics/metabolism ; Mutation ; *Poaceae/genetics/drug effects/enzymology ; Plant Weeds/genetics/drug effects/enzymology ; }, abstract = {The genus Alopecurus encompasses several weed species, including Alopecurus japonicus, Alopecurus aequalis, and Alopecurus myosuroides, which represent significant threats to agricultural productivity, particularly in wheat and oilseed rape fields. ALS-inhibiting herbicides have been extensively used for controlling Alopecurus weeds. However, the widespread use of these herbicides has led to the rapid emergence of resistance in Alopecurus populations with the Trp-574-Leu (W574L) mutation in the ALS gene being one of the most common resistance mechanisms. This study aims to develop a novel molecular detection method combining recombinase-aided amplification (RAA) with CRISPR/Cas12a technology to detect the W574L mutation in Alopecurus species. The method was optimized for key parameters, balancing efficiency with experimental costs, and was evaluated for specificity, sensitivity, and field applicability. This approach offers a rapid, accurate, and visual tool for identifying W574L target-site resistance in A. japonicus, A. aequalis, and A. myosuroides, with significant potential for monitoring resistance and enhancing weed management strategies.}, } @article {pmid40176466, year = {2025}, author = {Zhang, Y and Robinson, K and Xia, Y and Sun, J}, title = {Synergistic Effects of Riluzole and Sodium Butyrate on Barrier Function and Disease Progression of Amyotrophic Lateral Sclerosis Through the Gut-Neuron Axis.}, journal = {Comprehensive Physiology}, volume = {15}, number = {2}, pages = {e70009}, pmid = {40176466}, issn = {2040-4603}, support = {I01BX004824-06//U.S. Department of Veterans Affairs/ ; R01DK134343/NH/NIH HHS/United States ; R01 DK134343/DK/NIDDK NIH HHS/United States ; I01 BX004824/BX/BLRD VA/United States ; R01DK105118/NH/NIH HHS/United States ; R01DK114126/NH/NIH HHS/United States ; R01 DK105118/DK/NIDDK NIH HHS/United States ; R01 DK114126/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; *Riluzole/pharmacology/therapeutic use/administration & dosage ; *Amyotrophic Lateral Sclerosis/drug therapy/metabolism/physiopathology ; Mice ; *Butyric Acid/pharmacology/therapeutic use ; Disease Progression ; *Neuroprotective Agents/pharmacology ; Male ; Mice, Transgenic ; Drug Synergism ; Disease Models, Animal ; *Neurons/drug effects ; Superoxide Dismutase-1/genetics/metabolism ; }, abstract = {Emerging evidence has shown that gut-brain barrier dysfunction occurs at the early stages of ALS. Previous studies demonstrated that sodium butyrate significantly prolonged the life span of ALS mice. Riluzole is the first FDA-approved drug for ALS treatment. We hypothesize that Riluzole and sodium butyrate combined treatment further decreases aggregation of the h-SOD1[G93A], restores the gut-brain barrier function, and delays ALS progression. SOD1[G93A] mice (9-10-week-old) were treated with Riluzole (10 mg/kg, I.P. daily), sodium butyrate (2% in drinking water), or Riluzole and sodium butyrate combination for 6 weeks. The Riluzole/butyrate combination showed a significantly longer rotarod time, increased grip strength, and enhanced intestinal barrier, as compared with Riluzole or sodium butyrate-only treatment. More reduction of h-SOD1[G93A] aggregation was observed in the colon, spinal cord lumbar, and brain cortex with Riluzole and sodium butyrate combination, compared with Riluzole or sodium butyrate-only treatment. Tight junction proteins (ZO-1 and Claudin-5) significantly increased in the colon, spinal cord lumbar, and brain cortex of mice with Riluzole and sodium butyrate treatment. The Riluzole and sodium butyrate combination reduced serum lipopolysaccharides and h-SOD1[G93A] aggregation, and inflammatory cytokines more than those in Riluzole or sodium butyrate-only treatment. Overall, Riluzole and sodium butyrate treatment is more effective than either Riluzole or sodium butyrate-only in delaying ALS progress. It provides a potential therapeutic strategy and mechanism by restoring barrier function through the gut-brain axis for ALS.}, } @article {pmid40174325, year = {2025}, author = {Farndale, L and Insall, R and Yuan, K}, title = {TriDeNT : Triple deep network training for privileged knowledge distillation in histopathology.}, journal = {Medical image analysis}, volume = {102}, number = {}, pages = {103479}, doi = {10.1016/j.media.2025.103479}, pmid = {40174325}, issn = {1361-8423}, mesh = {Humans ; *Deep Learning ; Immunohistochemistry ; }, abstract = {Computational pathology models rarely utilise data that will not be available for inference. This means most models cannot learn from highly informative data such as additional immunohistochemical (IHC) stains and spatial transcriptomics. We present TriDeNT , a novel self-supervised method for utilising privileged data that is not available during inference to improve performance. We demonstrate the efficacy of this method for a range of different paired data including immunohistochemistry, spatial transcriptomics and expert nuclei annotations. In all settings, TriDeNT outperforms other state-of-the-art methods in downstream tasks, with observed improvements of up to 101%. Furthermore, we provide qualitative and quantitative measurements of the features learned by these models and how they differ from baselines. TriDeNT offers a novel method to distil knowledge from scarce or costly data during training, to create significantly better models for routine inputs.}, } @article {pmid40172690, year = {2025}, author = {Mathis, S and Beauvais, D and Duval, F and Barnay, M and Strub, V and Géfard-Gontier, E and Solé, G and Le Masson, G}, title = {When neuromuscular disorders become stars.}, journal = {Journal of neurology}, volume = {272}, number = {4}, pages = {305}, pmid = {40172690}, issn = {1432-1459}, mesh = {Humans ; *Neuromuscular Diseases/history ; Retrospective Studies ; History, 20th Century ; Motion Pictures/history ; }, abstract = {This retrospective study identified 125 audio-visual works from cinema and television, including films, TV series, and documentaries, depicting neuromuscular disorders since 1910. Motor neuron disorders, including amyotrophic lateral sclerosis (ALS), had the highest representation (69.3%), followed by myopathies (20%). The predominant genre was documentary (48%), which offered more factual representation than fictional works. ALS was overrepresented due to its dramatic nature and association with notable figures, including the American baseball player Lou Gehrig and British theoretical physicist Stephen Hawking; other neuromuscular disorders, such as Duchenne muscular dystrophy, were depicted less frequently. Despite inaccuracies in some portrayals, these works raise public awareness and contribute to a greater understanding of rare diseases, such as neuromuscular disorders, among the general public.}, } @article {pmid40171862, year = {2025}, author = {Bierowski, AE and Comber, PC and Kuc, A and Shah, A and Carroll, G}, title = {The Effect of Prehospital Protocol Modification during COVID-19 on First-Pass Intubation Success Rates.}, journal = {Prehospital and disaster medicine}, volume = {40}, number = {2}, pages = {73-76}, pmid = {40171862}, issn = {1945-1938}, mesh = {Humans ; *COVID-19/epidemiology ; *Intubation, Intratracheal/statistics & numerical data/standards/methods ; Retrospective Studies ; *Emergency Medical Services ; Male ; Female ; Middle Aged ; *Airway Management/methods ; *Clinical Protocols ; SARS-CoV-2 ; Adult ; Aged ; }, abstract = {INTRODUCTION: Many Emergency Medical Services (EMS) agencies modified their protocols during the height of the COVID-19 pandemic, particularly those involving procedures that lead to an increased risk of airborne exposure, such as intubation. In 2020, local Advanced Life Support (ALS) providers' first-line airway management device was the supraglottic airway (SGA), and tracheal intubations (TIs) were rarely performed.

OBJECTIVE: This study's aim was to investigate the potential clinical effect of this pandemic-related protocol change on first-pass TI success rates and on overall initial advanced airway placement success.

METHODS: This study was a retrospective prehospital chart review for all ALS encounters from a single urban EMS agency that resulted in the out-of-hospital placement of at least one advanced airway per encounter from January 1, 2019 through June 30, 2021 (n = 452). Descriptive statistics and chi square tests were used to evaluate data. Statistical significance was defined at P < .05.

RESULTS: Significantly fewer TIs were attempted in 2020 (n = 16) compared to 2019 (n = 80; P < .001), and first-pass TI success rates significantly decreased in 2021 (n = 22; 61.1%) compared to 2019 (n = 63; 78.8%; P = .047). Also, SGA placement constituted 91.2% of all initial airway management attempts in 2020 (n = 165), more than both 2019 (n = 114; 58.8%; P < .001) and 2021 (n = 87; 70.7%; P < .001). Overall first-attempt advanced airway placement success, encompassing both supraglottic and TI, increased from 2019 (n = 169; 87.1%) to 2020 (n = 170; 93.9%; P = .025). Conversely, overall first attempt advanced airway placement success decreased from 2020 to 2021 (n = 104; 84.6%; P = .0072).

CONCLUSIONS: Lack of exposure to TI during the COVID-19 pandemic likely contributed to this local agency's decreased first-pass TI success in 2021. Moving forward, agencies should utilize simulation labs and other continuing education efforts to help maintain prehospital providers' proficiency in performing this critical procedure, particularly when protocol changes temporarily hinder or prohibit field-based psychomotor skill development.}, } @article {pmid40171534, year = {2025}, author = {Burg, T and Tzeplaeff, L and Cassel, R and Lingor, P}, title = {Editorial: Innovative approaches to catalyze preclinical and clinical research on amyotrophic lateral sclerosis (ALS) and related disorders.}, journal = {Frontiers in neuroscience}, volume = {19}, number = {}, pages = {1582539}, pmid = {40171534}, issn = {1662-4548}, } @article {pmid40171495, year = {2024}, author = {Oviedo, BJ and Arroyo-Hernandez, J and Gutiérrez-Bolaños, MJ and Alvarado-Pérez, H and Mora-Monestel, E and Rojas-Alvarado, A and Álvarez-Valverde, V and Jiménez-Bonilla, P}, title = {Assesment of chemometric analysis utilizing Multivariate Curve Resolution Alternating Least Squares (MCRALS) for examination of thermal and photodegradation of fern extracts.}, journal = {BioInspired Processing (BIP), IEEE International Conference on}, volume = {2024}, number = {}, pages = {}, pmid = {40171495}, support = {D43 TW011403/TW/FIC NIH HHS/United States ; }, abstract = {This study focuses on refining Multivariate Curve Resolution-Alternating Least Squares (MCR-ALS) for chromatographic profiling to analyze chemical changes in Serpocaulon sessilifolium extracts from the Costa Rican rainforest. High-Performance Liquid Chromatography (HPLC) with a diode array detector (DAD) and Mass Detector were employed, where traditional analyses often discard valuable spectral data beyond the maximum absorption wavelength. To optimize the analysis, Principal Component Analysis (PCA) were used to select the optimal number of components for MCR-ALS. Fern extracts, stored under varying conditions -refrigeration, warm temperatures, and UV light exposure- are analyzed over time to study their chemical stability. The decomposition identifies key chemical constituents, revealing that warmer conditions and UV exposure accelerate degradation, with significant shifts in chemical composition observed over time. MCR-ALS analysis allows detailed tracking of chemical changes, showing emerging peaks and shifts in concentration, particularly in the more reactive compounds, enhancing resolution and overcoming challenges such as peak interference and co-elution. The study highlights the differences between UV-absorption data and mass spectrometry, where mass spectrometry offers more detailed resolution but requiring greater computational resources. The use of both methods provides a comprehensive understanding of the chemical dynamics of the extracts. This research demonstrates the potential of MCR-ALS, combined with advanced statistical tools, for improving chromatographic analysis and contributing to botanical and natural product research.}, } @article {pmid40171058, year = {2025}, author = {Husted, C and Tubman, G}, title = {Case Study: The Benefits of the Neubie Direct Current Electrical Stimulation Device for Pain, Spasticity, and Movement in Amyotrophic Lateral Sclerosis.}, journal = {Integrative medicine (Encinitas, Calif.)}, volume = {24}, number = {2}, pages = {25-29}, pmid = {40171058}, issn = {1546-993X}, abstract = {This case study reports the impact of the Neubie direct current electrical stimulation device in helping restore nerve conduction and function in a 65-year-old woman with sporadic ALS. Use of the Neubie began 12 months after her sudden onset of symptoms. By then, she could not move her fingers or toes, had drop foot, had lost considerable weight and muscle mass, and was in pain. After her first Neubie session, she could wiggle her toes and that movement persisted. After two months she had no hip pain and was moving her fingers, toes, hands, and feet. The Master Reset protocol was used to facilitate the calming of the nervous system and required a sequential increase of settings. She then developed tight, painful shoulders from being in a wheelchair and Neubie treatments on her shoulders ultimately allowed her to become pain-free and regain some range of motion to increase her shoulder flexibility. Her voice then became soft due to a weak diaphragm. After two months she could feel the Neubie treatments increase the innervation of her diaphragm. At the time of this data collection and work, she was pain-free, had increased movement and range of motion, and had more energy. She showed improvements in muscle activation and strength in her legs and was able to stand with assistance. The results of this case study support the need to further study the impact of the Neubie in ALS, especially early in the course of the disease.}, } @article {pmid40170896, year = {2025}, author = {Wang, Y and Mi, Y and Wang, H and Jiang, J and Mao, L and Heng, Y and Li, X and Deng, M}, title = {Combined impact of CHCHD10 p.Gly66Val and three other variants suggests oligogenic contributions to ALS.}, journal = {Frontiers in neurology}, volume = {16}, number = {}, pages = {1438207}, pmid = {40170896}, issn = {1664-2295}, abstract = {INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a severe neurodegenerative disease characterized by a progressive loss of motor neurons and muscle atrophy. Genetic factors are known to play important roles in ALS and concomitant presence of rare variants in ALS patients have been increasingly reported.

METHODS: In order to explore the genetic variants in ALS patients within the context of oligogenic inheritance and to elucidate the clinical heterogeneity observed in these patients, we conducted whole-genome sequencing on 34 familial ALS (FALS) probands.

RESULTS: In one proband, we identified a CHCHD10 p.Gly66Val variant, along with three additional variants: UNC13A p.Leu1034Val, SUSD1 p.Trp704Ser, and SQSTM1 p.His359del. This patient exhibited a slow disease progression and a prolonged survival duration, consistent with the clinical features of ALS patients with CHCHD10 variants. This suggests that the CHCHD10 p.Gly66Val variant may play a predominant role in shaping the patient's phenotype, while the other variants may primarily contribute to ALS occurrence.

DISCUSSION: Variants in CHCHD10 have been found in ALS and other neurodegenerative diseases, exhibiting significant clinical variability. However, the combinatorial effect of CHCHD10 and other ALS-related gene variants has not been fully studied. Our findings suggest that the combined impact of these four variants contributes to this patient's ALS phenotype, distinguishing it from other, less severe neuromuscular disorders associated with CHCHD10 mutations. Overall, this study further supports the oligogenic pathogenic basis of ALS and offers new insights into understanding the intricate clinical presentations associated with CHCHD10 variants.}, } @article {pmid40170672, year = {2025}, author = {Schneck, D and Arguedas, A and Xenopoulos-Oddsson, A and Arcila-Londono, X and Lunetta, C and Wymer, J and Olney, N and Gwathmey, K and Ajroud-Driss, S and Hayat, G and Heiman-Patterson, T and Cerri, F and Fournier, C and Glass, J and Sherman, A and Fiecas, M and Walk, D}, title = {Time-to-event prediction in ALS using a landmark modeling approach, using the ALS Natural History Consortium dataset.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {26}, number = {5-6}, pages = {417-425}, doi = {10.1080/21678421.2025.2482943}, pmid = {40170672}, issn = {2167-9223}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/therapy/physiopathology/epidemiology ; Male ; Female ; *Disease Progression ; Middle Aged ; Aged ; Longitudinal Studies ; Time Factors ; Noninvasive Ventilation ; }, abstract = {BACKGROUND AND OBJECTIVES: Times to clinically relevant events are a valuable outcome in observational and interventional studies, complementing linear outcomes such as functional rating scales and biomarkers. In ALS, there are several clinically relevant events. We developed dynamic prediction models for several of these times to events that can be used for clinical trial modeling and personal planning.

METHODS: Landmark time-to-event analysis was implemented to determine the effect of patient characteristics on disease progression. Longitudinal data from 1557 participants in the ALS Natural History Consortium dataset were used. Five outcomes in the ALS disease progression were considered: loss of ambulation, loss of speech, gastrostomy, noninvasive ventilation (NIV) use, and continuous NIV use. Covariates in our models include age at diagnosis, sex, onset location, riluzole use, diagnostic delay, ALSFRS-R scores at the landmark time, and ALSFRS-R rates of change from baseline. Internal and external validation techniques were used.

RESULTS: For each of our models and landmark times, we present risk prediction intervals for random sets of patient characteristics. We demonstrate our models' application for an individual's personal predicted time-to-event. Our internal and external validation metrics indicate good concordance and overall performance. The time to loss of speech models perform the best for each metric in terms of both internal and external validation.

DISCUSSION: Landmarking is an efficient, individualized risk prediction model that is intuitive for both clinicians and patients. Importantly, landmarking can be used for clinical trial modeling, personal planning, and development of real-world evidence of the impacts of treatment interventions.}, } @article {pmid40169784, year = {2025}, author = {Simonini, C and Zucchi, E and Martinelli, I and Gianferrari, G and Lunetta, C and Sorarù, G and Trojsi, F and Pepe, R and Piras, R and Giacchino, M and Banchelli, F and Mandrioli, J}, title = {Neurodegenerative and neuroinflammatory changes in SOD1-ALS patients receiving tofersen.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {11034}, pmid = {40169784}, issn = {2045-2322}, support = {Ricerca Corrente funding scheme of the Italian Ministry of Health//Ministero della Salute/ ; Ricerca Finalizzata bando 2021 (RF-2021-12373036)//Ministero della Salute/ ; bando FAR 2021, Progetti di ricerca Interdisciplinari Mission Oriented, NEURALS project)//Università Degli Studi di Modena e Reggio Emila/ ; Neurobiobanca di Modena//Fondazione Cassa di Risparmio di Modena/ ; }, mesh = {Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; alpha 1-Antitrypsin/cerebrospinal fluid/blood ; *Amyotrophic Lateral Sclerosis/drug therapy/genetics/pathology ; Biomarkers/cerebrospinal fluid/blood ; Chitinase-3-Like Protein 1/cerebrospinal fluid/blood ; Disease Progression ; Neurofilament Proteins/cerebrospinal fluid/blood ; *Neuroinflammatory Diseases ; *Oligonucleotides/therapeutic use ; *Superoxide Dismutase-1/genetics ; }, abstract = {The initiation of tofersen, a new specific antisense oligonucleotide (ASO) for SOD1 pathology, marked a significant turning point for SOD1-ALS patients. While clinical trials and early access program studies reported a significant reduction in plasma and cerebrospinal fluid (CSF) neurofilament levels, neuroinflammation following prolonged treatment was never assessed. In this multicenter study, we evaluated a cohort of 18 SOD1-ALS patients treated with tofersen, analyzing correlations between biomarkers of neurodegeneration/neuroinflammation and clinical variables indicative of disease progression. NfL, NfH, CHI3L1, and Serpina1 levels in serum and CSF were determined by semi-automated immunoassays (Ella™ technology). Generalized linear mixed models were employed to investigate longitudinal trends of these biomarkers. Our data highlighted a progressive decrease in CSF neurofilament levels during tofersen treatment (MR = 0.97, 95% CI 0.94-0.99, p = 0.006 and MR = 0.98, 95% CI 0.95-1.00, p = 0.076 for NfL and NfH in CSF, respectively). Conversely, CSF levels of SerpinA1 and CHI3L1 increased over time (MR = 1.12, 95% CI 1.08-1.16, p < 0.0001 and MR = 1.039, 95% CI 1.015-1.062, p = 0.001 for SerpinA1 and CHI3L1 in CSF, respectively), but these modifications were most apparent after six and twelve months of therapy, respectively. Disease progression rate did not correlate with these biomarker trends. We observed a significant decrease in neurofilament levels during Tofersen treatment, alongside an increase in neuroinflammatory markers, potentially linked to an immune response triggered by ASO treatment. Given the limited data on tofersen's long-term efficacy in ALS due to its recent introduction, identifying biomarkers that predict clinical outcomes such as diminished therapeutic response or adverse effects is crucial. These biomarkers may help to better understand the underlying pathomechanisms of ALS and tofersen's role in modulating disease progression.}, } @article {pmid40169635, year = {2025}, author = {D'Amico, A and Cucunato, R and Salemi, G and Bella, V and Aridon, P}, title = {A population based study to analyse amyotrophic lateral sclerosis as a multi-step process.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {11189}, pmid = {40169635}, issn = {2045-2322}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/epidemiology/pathology/genetics ; Female ; Male ; Middle Aged ; Aged ; Adult ; Sicily/epidemiology ; Incidence ; Disease Progression ; }, abstract = {Recent studies suggest that Amyotrophic Lateral Sclerosis (ALS) follows a multistep process. We evaluated this hypothesis in a well-defined ALS population in Palermo, Sicily, almost entirely followed by our ALS Clinical Center. Incident data from the ALS Center (2014-2023) were analyzed, including both sporadic and familial ALS forms of the disease. To evaluate the multistep process, we regressed the natural log of age-specific incidence against the natural log of patient age We identified 216 ALS patients. We obtained a slope of 5 (r[2] = 0.93); the 95% CI ranged from 2.51 to 7.60, remaining relatively wide due to the small sample size, with a p-value of 0.008. The slope estimate was consistent with a 6-step process. In the Palermo ALS population, the multistep analysis confirms a process consistent with a 6-step model. This data, obtained in a relatively homogeneous population, further highlights the probability of strict interaction between environmental and genetic variables in the disease. Our data offer insights into the complexity of the mechanisms involved in the pathogenesis of the disease, particularly during its asymptomatic phase. This study supports the hypothesis that a single therapeutic silver bullet would probably be insufficient to arrest or slow the disease's progression.}, } @article {pmid40169538, year = {2025}, author = {Iyer, KA and Tenchov, R and Sasso, JM and Ralhan, K and Jotshi, J and Polshakov, D and Maind, A and Zhou, QA}, title = {Rare Diseases, Spotlighting Amyotrophic Lateral Sclerosis, Huntington's Disease, and Myasthenia Gravis: Insights from Landscape Analysis of Current Research.}, journal = {Biochemistry}, volume = {64}, number = {8}, pages = {1698-1719}, pmid = {40169538}, issn = {1520-4995}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/therapy/pathology/metabolism ; *Myasthenia Gravis/genetics/therapy/pathology/metabolism ; *Rare Diseases/genetics/therapy ; *Huntington Disease/genetics/therapy/pathology/metabolism ; Animals ; }, abstract = {Rare diseases are a diverse group of disorders that, despite each individual condition's rarity, collectively affect a significant portion of the global population. Currently approximately 10,000 rare diseases exist globally, with 80% of these diseases being identified as having genetic origins. In this Review, we examine data from the CAS Content Collection to summarize scientific progress in the area of rare diseases. We examine the publication landscape in the area in an effort to provide insights into current advances and developments. We then discuss the evolution of key concepts in the field, genetic associations, as well as the major technologies and development pipelines of rare disease treatments. We focus our attention on three specific rare diseases: (i) amyotrophic lateral sclerosis, a terminal neurodegenerative disease affecting the central nervous system resulting in progressive loss of motor neurons that control voluntary muscles; (ii) Huntington's disease, another terminal neurodegenerative disease that causes progressive degeneration of nerve cells in the brain, with a wide impact on a person's functional abilities; and (iii) myasthenia gravis, a chronic autoimmune synaptopathy leading to skeletal muscle weakness. While the pathogenesis of these rare diseases is being elucidated, there is neither a cure nor preventative treatment available, only symptomatic treatment. The objective of the paper is to provide a broad overview of the evolving landscape of current knowledge on rare diseases and specifically on the biology and genetics of the three spotlighted diseases, to outline challenges and evaluate growth opportunities, an aim to further efforts in solving the remaining challenges.}, } @article {pmid40169452, year = {2025}, author = {Hou, X and Jiang, J and Deng, M}, title = {Exploring epigenetic modifications as potential biomarkers and therapeutic targets in amyotrophic lateral sclerosis.}, journal = {Journal of neurology}, volume = {272}, number = {4}, pages = {304}, pmid = {40169452}, issn = {1432-1459}, support = {82273915//National Natural Science Foundation of China/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/therapy/metabolism/diagnosis ; *Epigenesis, Genetic ; Biomarkers/metabolism ; DNA Methylation ; Animals ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder and the most common motor neuron disease. Whole-genome sequencing has identified many novel ALS-associated genes, but genetics alone cannot fully explain the onset of ALS and an effective treatment is still lacking. Moreover, we need more biomarkers for accurate diagnosis and assessment of disease prognosis. Epigenetics, which includes DNA methylation and hydroxymethylation, histone modifications, chromatin remodeling, and non-coding RNAs, influences gene transcription and expression by affecting chromatin accessibility and transcription factor binding without altering genetic information. These processes play a role in the onset and progression of ALS. Epigenetic targets can serve as potential biomarkers and more importantly, the reversibility of epigenetic changes supports their potential role as versatile therapeutic targets in ALS. This review summarized the alterations in different epigenetic modulations in ALS. Additionally, given the close association between aberrant metabolic profiles characterized by hypoxia and high glycolytic metabolism in ALS and epigenetic changes, we also integrate epigenetics with metabolomics. Finally, we discuss the application of therapies based on epigenetic mechanisms in ALS. Our data integration helps to identify potential diagnostic and prognostic biomarkers and support the development of new effective therapies.}, } @article {pmid40167598, year = {2025}, author = {Shi, Y and Wan, Y and Wang, Y and Fang, K and Yang, J and Lu, Y and Xie, X and Pan, J and Gao, D and Wang, H and Qu, H}, title = {Quantitative [1]H NMR optimization for high-throughput metabolite analysis in industrial bioprocess monitoring.}, journal = {Analytical and bioanalytical chemistry}, volume = {417}, number = {14}, pages = {3047-3059}, pmid = {40167598}, issn = {1618-2650}, support = {2023C03116//Key Research and Development Program of Zhejiang Province/ ; }, mesh = {CHO Cells ; Cricetulus ; Animals ; *High-Throughput Screening Assays/methods ; *Proton Magnetic Resonance Spectroscopy/methods ; Limit of Detection ; *Metabolomics/methods ; Cricetinae ; }, abstract = {Quantitative [1]H NMR ([1]H qNMR) is an ideal tool for bioprocess monitoring because it can comprehensively detect and quantify diverse metabolites that significantly influence bioprocess performance. However, the long experiment time associated with the [1]H qNMR, due to the long longitudinal relaxation time (T1) of some metabolites, does not meet the requirements for high-throughput analysis. We developed a high-throughput [1]H qNMR method for bioprocess analysis using a short relaxation delay (D1) to reduce analytical time and a correction factor (k) to compensate for incomplete relaxation. A total of 27 metabolites were quantified using spectral deconvolution via a peak fitting algorithm and MCR-ALS. Methodological validation results indicated that the precision and accuracy of the developed qNMR method were consistently high across different D1 values, with LOQs ranging from 0.008 to 0.13 mM and LODs ranging from 0.024 to 0.38 mM. Notably, a longer D1 value generally resulted in lower LODs and LOQs for most metabolites. A D1 value of 4 s was optimal for balancing analysis time and performance. The method is broadly applicable for bioprocess monitoring and control, offering valuable guidance for optimizing CHO cell culture processes and improving yield.}, } @article {pmid40166719, year = {2025}, author = {Xiong, J and Chen, X and Huang, K and Pan, Y}, title = {Successful Guselkumab Treatment in a Patient with Comorbid Psoriasis and Amyotrophic Lateral Sclerosis: A Case Study and Literature Review.}, journal = {Clinical, cosmetic and investigational dermatology}, volume = {18}, number = {}, pages = {735-741}, pmid = {40166719}, issn = {1178-7015}, abstract = {Psoriasis is genetically influenced and can be triggered by factors such as infections, stress, and lifestyle. Chronic plaque psoriasis, the most prevalent form, involves key roles for IL-17 and IL-23 in its pathogenesis. Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by the degeneration of motor neurons, resulting in muscle weakness and atrophy. Currently, there is no cure for ALS, and treatment is symptomatic, aimed at improving quality of life. The combination of psoriasis and ALS is relatively rare. Although biologic agents have shown remarkable efficacy in the treatment of chronic plaque psoriasis, we have not found any case reports regarding the use of biologic agents for treating psoriasis accompanied by ALS. Our study presents a patient with severe plaque psoriasis and ALS who exhibited a positive response to Guselkumab, without worsening of ALS symptoms, suggesting a promising therapeutic strategy. This could provide a treatment option for patients with psoriasis combined with ALS.We conducted a comprehensive review of the literature on the comorbidity of neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), and ALS, with plaque psoriasis. This review highlights the differential impact of treatment modalities. Specifically, we found that TNF-α inhibitors may have adverse effects in MS but could provide protective benefits in AD and PD. In ALS patients with psoriasis, IL-17A and IL-23 inhibitors, exemplified by Guselkumab, are suggested as a more suitable alternative due to their lower risk of worsening ALS symptoms.}, } @article {pmid40166606, year = {2025}, author = {de-Winton Cummings, PJ and Gonzalez Bravo, C and Dukes, KC and Wilks, AD and Ahlers, CD and Casado Castillo, FE and Courtney, A and Elliott-Wherry, AN and Knobbe, JE and Pineiro-Falcon, NM and Schaeffer, SE and Tillinghast, S and Tovar, EF and Villa, AT and Carvour, ML}, title = {Modifiable social and structural factors influence COVID-19 vaccine intention among frontline workers in the Midwestern USA: a community-engaged survey study.}, journal = {BMJ public health}, volume = {3}, number = {1}, pages = {e000859}, pmid = {40166606}, issn = {2753-4294}, support = {KL2 TR002536/TR/NCATS NIH HHS/United States ; T32 AI007485/AI/NIAID NIH HHS/United States ; T32 GM139776/GM/NIGMS NIH HHS/United States ; UM1 TR004403/TR/NCATS NIH HHS/United States ; }, abstract = {INTRODUCTION: COVID-19 vaccines have been a crucial measure in the pandemic response, yet vaccine uptake has been variable across the population. We sought to identify social and structural factors associated with COVID-19 vaccine intention among adults in the Midwestern USA who worked in one or more frontline industries during the COVID-19 pandemic.

METHODS: A community-engaged, cross-sectional online survey study was conducted between May and July 2022 among 889 workers. Guided by Thomas and Penchasky's 5As theory of access and Thomson et al's 5As taxonomy of vaccine uptake, we assessed modifiable social and structural factors related to access (transportation and convenient locations), affordability (time and incentives), activation (reminders), acceptability (experiences in a healthcare setting, political confidence and vaccine confidence) and accommodation (language inclusion and flexible appointments). Multinomial logistic regression was used to identify potentially modifiable factors that may influence vaccine intention among more than 200 surveyed workers who had not yet been vaccinated.

RESULTS: Workers who intended not to receive the vaccine were at least three times more likely to report transportation challenges, limited time off work and inflexible vaccine appointments compared with those who intended to vaccinate. Interest in financial incentives was strongly endorsed among workers who did not intend to vaccinate and among those who were undecided. Concerns about vaccine safety or side effects did not influence intention, whereas concerns about vaccine effectiveness were more common among workers who did not intend to vaccinate. Mistrust in government leaders was associated with positive vaccine intention.

CONCLUSIONS: Vaccine intention among frontline workers is strongly influenced by social and structural factors and not solely by hesitancy about the vaccine itself.}, } @article {pmid40166559, year = {2025}, author = {Lorincz-Comi, N and Cheng, F}, title = {Bayesian inference of genetic pleiotropy identifies drug targets and repurposable medicines for human complex diseases.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, pmid = {40166559}, support = {R21 AG083003/AG/NIA NIH HHS/United States ; R01 AG082118/AG/NIA NIH HHS/United States ; R56 AG074001/AG/NIA NIH HHS/United States ; RF1 AG082211/AG/NIA NIH HHS/United States ; R01 AG084250/AG/NIA NIH HHS/United States ; RF1 NS133812/NS/NINDS NIH HHS/United States ; U01 AG073323/AG/NIA NIH HHS/United States ; R01 AG066707/AG/NIA NIH HHS/United States ; R01 AG076448/AG/NIA NIH HHS/United States ; }, abstract = {Complex diseases share heritable components which can be leveraged to identify drug targets with low side effect or high repurposing potential, but current methods cannot efficiently make these inferences at scale using public data. We introduce a Bayesian model to estimate the polygenic structure of a trait using GWAS summary data (BPACT). Across 32 complex traits, we estimated that 69.5 to 97.5% of disease-associated druggable genes are shared between multiple traits. We observed that targeting KIT for ALS prevention may increase triglyceride levels, but that targeting TBK1 and SCN11B may be safer because of they were not pleiotropic. We additionally found 21 candidate repurposable drug targets for Alzheimer's disease (AD) (e.g., PLEKHA1, PPIB) and 5 for ALS (e.g., GAK, DGKQ) based on the directionality of their pleiotropy. Our results demonstrate that modeling shared genetic architecture across traits can uncover safer therapeutic targets and highlight opportunities for drug repurposing in complex diseases.}, } @article {pmid40165742, year = {2025}, author = {Fernández Soberón, S and Gómez Escobar, T and Caravaca Puchades, A and Andrés-Benito, P and Vázquez-Costa, JF and Mora Pardina, J and Juntas Morales, R and Povedano, M}, title = {Yentl syndrome, a real phenomenon in amyotrophic lateral sclerosis (ALS)?.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {26}, number = {3-4}, pages = {211-214}, doi = {10.1080/21678421.2024.2432030}, pmid = {40165742}, issn = {2167-9223}, mesh = {Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; *Amyotrophic Lateral Sclerosis/epidemiology/diagnosis ; Databases, Factual ; Retrospective Studies ; Spain/epidemiology ; }, abstract = {Introduction: ALS, a neurodegenerative disorder, exhibits variable incidence and prevalence across various databases consulted. Among these, PRO-ACT stands out as the most extensive publicly accessible repository of aggregated ALS clinical trial information. The estimated male-female ratio is greater for men at younger ages, which tends to equalize with aging. If specific measures are not taken to address this, this higher male prevalence could result in a higher inclusion of men in clinical trials, which could lead to biases in the observed results, preventing the proper assessment of differences between sexes. Our aim was to describe the demographic dates of the population included in ALS clinical trials in the last 8 years at Spanish national reference centers, with special interest in female participation. Methodology: Retrospective and descriptive observational study using databases of national reference centers. Results: We analyzed the databases of 4 neurological Spanish reference centers during a period of 8 years. A total number of 426 subjects were included. A greater participation of the male sex was evident in all the studies evaluated, representing 64.55% of the subjects included. This predominance has not varied significantly over the last 8 years. Our results correlate with the data published in PRO-ACT to date, where men represent 60% of the total number of participants. Conclusion: The predominance of the male sex in ALS clinical trials is a consistent and invariable finding and is known as Yentl's syndrome. This phenomenon prevents the principle of neutrality of medicine, allowing for purely partial knowledge.}, } @article {pmid40164574, year = {2025}, author = {Gómez-Gálvez, P and Navarro, V and Castro, AM and Paradas, C and Escudero, LM}, title = {Computational Analysis of SOD1-G93A Mouse Muscle Biomarkers for Comprehensive Assessment of ALS Progression.}, journal = {Neuropathology and applied neurobiology}, volume = {51}, number = {2}, pages = {e70014}, doi = {10.1111/nan.70014}, pmid = {40164574}, issn = {1365-2990}, support = {//Margarita Salas Fellowship - NextGenerationEU/ ; CB18/05/00028//Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas/ ; PI13/01347//National Institute of Health Carlos III/ ; PI23/01892//National Institute of Health Carlos III/ ; FORT23/00008//National Institute of Health Carlos III/ ; }, mesh = {Animals ; *Amyotrophic Lateral Sclerosis/pathology/genetics ; *Muscle, Skeletal/pathology ; Disease Progression ; Mice ; Disease Models, Animal ; Mice, Transgenic ; Biomarkers ; Superoxide Dismutase-1/genetics ; Superoxide Dismutase/genetics ; }, abstract = {AIMS: To identify potential image biomarkers of neuromuscular disease by analysing morphological and network-derived features in skeletal muscle biopsies from a murine model of amyotrophic lateral sclerosis (ALS), the SOD1[G93A] mouse and wild-type (WT) controls at distinct stages of disease progression.

METHODS: Using the NDICIA computational framework, we quantitatively evaluated histological differences between skeletal muscle biopsies from SOD1[G93A] and WT mice. The process involved the selection of a subset of features revealing these differences. A subset of discriminative features was selected to characterise these differences, and their temporal dynamics were assessed across disease stages.

RESULTS: Our findings demonstrate that muscle pathology in the mutant model evolves from early alterations in muscle fibre arrangement, detectable at the presymptomatic stage through graph theory features, to the subsequent development of the typical morphological pattern of neurogenic atrophy at more advanced disease stages.

CONCLUSIONS: Our assay identifies a neurogenic signature in mutant muscle biopsies, even when the disease is phenotypically imperceptible.}, } @article {pmid40163151, year = {2025}, author = {Wadan, AS and Shaaban, AH and El-Sadek, MZ and Mostafa, SA and Moshref, AS and El-Hussein, A and Ellakwa, DE and Mehanny, SS}, title = {Mitochondrial-based therapies for neurodegenerative diseases: a review of the current literature.}, journal = {Naunyn-Schmiedeberg's archives of pharmacology}, volume = {}, number = {}, pages = {}, pmid = {40163151}, issn = {1432-1912}, abstract = {Neurodegenerative disorders present significant challenges to modern medicine because of their complex etiology, pathogenesis, and progressive nature, which complicate practical treatment approaches. Mitochondrial dysfunction is an important contributor to the pathophysiology of various neurodegenerative illnesses, including Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). This review paper examines the current literature highlighting the multifaceted functions of mitochondria, including energy production, calcium signaling, apoptosis regulation, mitochondrial biogenesis, mitochondrial dynamics, axonal transport, endoplasmic reticulum-mitochondrial interactions, mitophagy, mitochondrial proteostasis, and their crucial involvement in neuronal health. The literature emphasizes the increasing recognition of mitochondrial dysfunction as a critical factor in the progression of neurodegenerative disorders, marking a shift from traditional symptom management to innovative mitochondrial-based therapies. By discussing mitochondrial mechanisms, including mitochondrial quality control (MQC) processes and the impact of oxidative stress, this review highlights the need for novel therapeutic strategies to restore mitochondrial function, protect neuronal connections and integrity, and slow disease progression. This comprehensive review aims to provide insights into potential interventions that could transform the treatment landscape for neurodegenerative diseases, addressing symptoms and underlying pathophysiological changes.}, } @article {pmid40162390, year = {2025}, author = {Xie, Y and Xie, H and Wang, RL}, title = {Enhancing palliative care in malignant obstructive jaundice: A critical care perspective on endoscopic biliary stenting.}, journal = {World journal of gastrointestinal surgery}, volume = {17}, number = {3}, pages = {103431}, pmid = {40162390}, issn = {1948-9366}, abstract = {This letter responds to Wang et al's recent publication on endoscopic biliary stenting for malignant obstructive jaundice (MOJ) by offering constructive feedback and suggestions for future research. We commend the authors for their comprehensive study design and execution, which included a clear delineation of study groups and a robust set of outcome measures. We suggest that future studies incorporate additional biomarkers, such as serum levels of liver enzymes and bilirubin, to provide a more nuanced understanding of liver function changes post-intervention. The study's focus on short-term survival rates is appreciated, but we recommend exploring longer-term follow-up periods to capture the full spectrum of survival outcomes. Additionally, the inclusion of quality of life assessments using validated instruments could offer a more holistic view of patient outcomes. From a critical care perspective, we advocate for the integration of advanced imaging techniques to better characterize biliary anatomy and potentially predict treatment response or complications. We believe that incorporating these suggestions could enhance the understanding of endoscopic biliary stenting's role in MOJ management and its impact on patient outcomes, influencing future clinical guidelines and practice.}, } @article {pmid40161216, year = {2025}, author = {Scarcella, S and Brambilla, L and Quetti, L and Rizzuti, M and Melzi, V and Galli, N and Sali, L and Costamagna, G and Comi, GP and Corti, S and Gagliardi, D}, title = {Unveiling amyotrophic lateral sclerosis complexity: insights from proteomics, metabolomics and microbiomics.}, journal = {Brain communications}, volume = {7}, number = {2}, pages = {fcaf114}, pmid = {40161216}, issn = {2632-1297}, abstract = {Amyotrophic lateral sclerosis is the most common motor neuron disease and manifests as a clinically and genetically heterogeneous neurodegenerative disorder mainly affecting the motor systems. To date, despite promising results and accumulating knowledge on the pathomechanisms of amyotrophic lateral sclerosis, a specific disease-modifying treatment is still not available. In vitro and in vivo disease models coupled with multiomics techniques have helped elucidate the pathomechanisms underlying this disease. In particular, omics approaches are powerful tools for identifying new potential disease biomarkers that may be particularly useful for diagnosis, prognosis and assessment of treatment response. In turn, these findings could support physicians in stratifying patients into clinically relevant subgroups for the identification of the best therapeutic targets. Here, we provide a comprehensive review of the most relevant literature highlighting the importance of proteomics approaches in determining the role of pathogenic misfolded/aggregated proteins and the molecular mechanisms involved in the pathogenesis and progression of amyotrophic lateral sclerosis. In addition, we explored new findings arising from metabolomic and lipidomic studies, which can aid to elucidate the intricate metabolic alterations underlying amyotrophic lateral sclerosis pathology. Moreover, we integrated these insights with microbiomics data, providing a thorough understanding of the interplay between metabolic dysregulation and microbial dynamics in disease progression. Indeed, a greater integration of these multiomics data could lead to a deeper understanding of disease mechanisms, supporting the development of specific therapies for amyotrophic lateral sclerosis.}, } @article {pmid40159068, year = {2025}, author = {Wang, HF and Wang, HR and Lin, YC and Bai, JM and Li, M and Huang, XS}, title = {[Analysis of serum 25-hydroxyvitamin D3 levels and prognosis in patients with amyotrophic lateral sclerosis].}, journal = {Zhonghua nei ke za zhi}, volume = {64}, number = {4}, pages = {325-332}, doi = {10.3760/cma.j.cn112138-20240728-00481}, pmid = {40159068}, issn = {0578-1426}, support = {2023124//Tianjin Municipal Health and Health Commission Traditional Chinese Medicine and Integrative Medicine Research Project/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/blood/diagnosis ; Prognosis ; Male ; Female ; Middle Aged ; *Calcifediol/blood ; Prospective Studies ; Cross-Sectional Studies ; Risk Factors ; Aged ; Biomarkers/blood ; }, abstract = {Objective: To evaluate serum 25-hydroxyvitamin D3 [25(OH)D3] as a potential biomarker for amyotrophic lateral sclerosis (ALS) severity and to identify risk factors influencing ALS prognosis. Methods: This study included 217 ALS patients hospitalized at the Department of Neurology, First Medical Center, Chinese PLA General Hospital, between October 2018 and October 2021, who met the revised El Escorial diagnostic criteria. A cross-sectional analysis assessed differences in clinical indicators-including the ALS Functional Rating Scale-Revised (ALSFRS-R) and forced vital capacity percentage (FVC%)-across different serum 25(OH)D3 levels. The correlation between 25(OH)D3 levels and individual ALSFRS-R components was also examined. Conduct a prospective cohort study to identify independent risk factors affecting the survival time of ALS patients. Results: Among three groups categorized by serum 25(OH)D3 levels, there were significant differences in the proportion of males (χ[2]=10.51, P<0.05). Serum 25(OH)D3 levels correlated positively with lower limb function scores in the ALSFRS-R (r=0.05, P<0.05), but they were not identified as an independent risk factor for survival (HR=0.98, 95%CI 0.93-1.04, P>0.05). In contrast, delayed diagnosis(HR=0.94, 95%CI 0.89-0.99, P<0.05) and reduced FVC%(HR=0.94, 95%CI 0.97-0.99, P<0.05) were independent predictors of shorter survival. Conclusion: Serum 25(OH)D3 levels differ by gender distribution and may be linked to better lower limb function in ALS patients. However, their role in prolonging survival remains uncertain.}, } @article {pmid40157939, year = {2025}, author = {Rossi, S and Milani, M and Della Valle, I and Bisegna, S and Durante, V and Addesse, M and D'Avorio, E and Di Salvio, M and Serafino, A and Cestra, G and Apolloni, S and D'Ambrosi, N and Cozzolino, M}, title = {Cytoplasmic accumulation of a splice variant of hnRNPA2/B1 contributes to FUS-associated toxicity in a mouse model of ALS.}, journal = {Cell death & disease}, volume = {16}, number = {1}, pages = {219}, pmid = {40157939}, issn = {2041-4889}, support = {Nutrage, IFT DBA.AD005.225//Consiglio Nazionale delle Ricerche (National Research Council)/ ; SpliceALS//Fondazione Italiana di Ricerca per la Sclerosi Laterale Amiotrofica (Italian Research Foundation for ALS)/ ; SwitchALS//Fondazione Italiana di Ricerca per la Sclerosi Laterale Amiotrofica (Italian Research Foundation for ALS)/ ; }, mesh = {Animals ; *Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology ; *Heterogeneous-Nuclear Ribonucleoprotein Group A-B/metabolism/genetics ; *RNA-Binding Protein FUS/metabolism/genetics ; Disease Models, Animal ; Mice ; *Cytoplasm/metabolism ; Humans ; *Alternative Splicing/genetics ; Motor Neurons/metabolism/pathology ; Exons ; Stress Granules/metabolism ; }, abstract = {Genetic and experimental findings point to a crucial role of RNA dysfunction in the pathogenesis of Amyotrophic Lateral Sclerosis (ALS). Evidence suggests that mutations in RNA binding proteins (RBPs) such as FUS, a gene associated with ALS, affect the regulation of alternative splicing. We have previously shown that the overexpression of wild-type FUS in mice, a condition that induces ALS-like phenotypes, impacts the splicing of hnRNP A2/B1, a protein with key roles in RNA metabolism, suggesting that a pathological connection between FUS and hnRNP A2/B1 might promote FUS-associated toxicity. Here we report that the expression and distribution of different hnRNP A2/B1 splice variants are modified in the affected tissues of mice overexpressing wild-type FUS. Notably, degenerating motor neurons are characterized by the cytoplasmic accumulation of splice variants of hnRNP A2/B1 lacking exon 9 (hnRNP A2b/B1b). In vitro studies show that exon 9 skipping affects the nucleocytoplasmic distribution of hnRNP A2/B1, promoting its localization into stress granules (SGs), and demonstrate that cytoplasmic localization is the primary driver of hnRNP A2b recruitment into SGs and cell toxicity. Finally, boosting exon 9 skipping using splicing switching oligonucleotides exacerbates disease phenotypes in wild-type FUS mice. Altogether, these findings reveal that alterations of the nucleocytoplasmic distribution of hnRNP A2/B1, driven by FUS-induced splicing changes, likely contribute to motor neuron degeneration in ALS.}, } @article {pmid40157684, year = {2025}, author = {Yu, T and Li, M and Li, M and Zhang, Q and Zhang, H and Jiang, Z and Wang, S and Mao, H and Li, D and Fan, L and Hu, C and Xu, X}, title = {Zebrafish TDP43 positively regulates p65-mediated apoptotic pathway.}, journal = {International journal of biological macromolecules}, volume = {308}, number = {Pt 3}, pages = {142599}, doi = {10.1016/j.ijbiomac.2025.142599}, pmid = {40157684}, issn = {1879-0003}, mesh = {Animals ; *Zebrafish/metabolism/genetics/virology ; *Apoptosis/genetics ; *DNA-Binding Proteins/metabolism/genetics ; *Transcription Factor RelA/metabolism ; *Zebrafish Proteins/metabolism/genetics ; Signal Transduction ; Reoviridae/physiology ; Rhabdoviridae ; Reactive Oxygen Species/metabolism ; Phosphorylation ; Humans ; }, abstract = {TAR DNA-binding protein 43 (TDP43) is a multifunctional RNA/DNA binding protein that serves as a hallmark of neurodegeneration in amyotrophic lateral sclerosis (ALS) and is associated with the inflammatory response related to nuclear factor κB (NF-κB) pathway. However, the relationship between TDP43 and NF-κB is not well known. In this study, zebrafish TDP43 (DrTDP43) can be induced by grass carp reovirus (GCRV) or spring viremia of carp virus (SVCV). DrTDP43 enhances the nuclear factor-kappaB (NF-κB) activity and the expression of p65 and TNFα, as well as promotes the phosphorylation of p65 in response to stimulation of GCRV and SVCV. Further assays indicate that DrTDP43 primarily resides in the nucleus and interacts with p65 via its RRM1. DrTDP43 is required for p65 to induce pro-inflammatory cytokine production (IL-6, IL-10, TNFα, IL-1β). It disrupts mitochondrial membrane potential and exacerbates apoptosis via downregulating Bcl2 and upregulating Bax, caspase3, and eIF2α. Moreover, knockdown of TDP43 decreases the content of reactive oxygen species (ROS) and the number of apoptotic cells in zebrafish larvae, which is attributed to the lower lever of p65 phosphorylation and expression of TNFα, Bax and cleaved-caspase3. In a word, these results establish TDP43 as a critical activator of the NF-κB-mediated apoptotic pathway during antiviral responses, which reveals a previously unrecognized host defense mechanism.}, } @article {pmid40157434, year = {2025}, author = {Pu, L and Steele, JR and Phillips, CR and Violi, JP and Rodgers, KJ}, title = {The cyanobacterial toxins BMAA and 2,4-DAB perturb the l-serine biosynthesis pathway and induce systemic changes in energy metabolism in human neuroblastoma cells: A proteomic study.}, journal = {Toxicology in vitro : an international journal published in association with BIBRA}, volume = {106}, number = {}, pages = {106058}, doi = {10.1016/j.tiv.2025.106058}, pmid = {40157434}, issn = {1879-3177}, mesh = {*Amino Acids, Diamino/toxicity ; Humans ; Cyanobacteria Toxins ; *Serine/biosynthesis ; Energy Metabolism/drug effects ; Cell Line, Tumor ; Proteomics ; Neuroblastoma/metabolism ; *Aminobutyrates/toxicity ; *Bacterial Toxins/toxicity ; }, abstract = {Blue-green algae (cyanobacteria), an ancient phylum of bacteria, produce a wide array of secondary metabolites that are toxic to humans. Rapid growth of cyanobacteria in an aquatic environment can result in algal blooms capable of turning waterways green and increasing toxin levels in the environment. Cyanobacterial toxins were first linked to the high incidence of a complex neurodegenerative disorder reported on the island of Guam in the 1940s but more recently have been linked to clusters of sporadic amyotrophic lateral sclerosis (sALS) worldwide. The non-protein amino acid β-N-methylamino-L-alanine (BMAA) and its isomer L-2,4-diaminobutyric acid (2,4-DAB) are produced concurrently by most cyanobacterial species. We carried out proteomic analysis on human neuroblastoma cells treated with BMAA and 2,4-DAB to determine the underlying mechanisms of toxicity resulting from exposure to these cyanotoxins and identified significant changes in the l-serine biosynthesis pathway as well as pathways associated with energy production in the cell such as fatty acid ß-oxidation and glycolysis. The impact on the serine biosynthetic pathway was supported by demonstrating a significant decrease in both mRNA and protein levels of the enzyme 3-phosphoglycerate dehydrogenase (PHGDH) the first committed step in serine biosynthesis. PHGDH uses 3-phospho-D-glycerate (3PG) an intermediate in the glycolytic pathway as a substrate, and co-incubation of cells with l-serine restored expression levels of PHGDH as did cell pre-treatment with the glycolytic product pyruvate. This is the first study to link exposure to BMAA and 2,4-DAB to impairments in the l-serine biosynthesis pathway and broad disturbances in energy metabolism.}, } @article {pmid40157356, year = {2025}, author = {Rummens, J and Khalil, B and Yıldırım, G and Silva, P and Zorzini, V and Peredo, N and Wojno, M and Ramakers, M and Van Den Bosch, L and Van Damme, P and Davie, K and Hendrix, J and Rousseau, F and Schymkowitz, J and Da Cruz, S}, title = {TDP-43 seeding induces cytoplasmic aggregation heterogeneity and nuclear loss of function of TDP-43.}, journal = {Neuron}, volume = {113}, number = {10}, pages = {1597-1613.e8}, doi = {10.1016/j.neuron.2025.03.004}, pmid = {40157356}, issn = {1097-4199}, mesh = {Humans ; *DNA-Binding Proteins/metabolism/genetics ; Induced Pluripotent Stem Cells/metabolism ; *Cytoplasm/metabolism/pathology ; *Cell Nucleus/metabolism/pathology ; *Neurons/metabolism/pathology ; *Protein Aggregation, Pathological/metabolism/pathology ; TDP-43 Proteinopathies/metabolism/pathology ; Amyloid/metabolism ; Inclusion Bodies/metabolism ; Protein Aggregates ; }, abstract = {Cytoplasmic aggregation and nuclear depletion of TAR DNA-binding protein 43 (TDP-43) are hallmarks of several neurodegenerative disorders. Yet, recapitulating both features in cellular systems has been challenging. Here, we produced amyloid-like fibrils from recombinant TDP-43 low-complexity domain and demonstrate that sonicated fibrils trigger TDP-43 pathology in human cells, including induced pluripotent stem cell (iPSC)-derived neurons. Fibril-induced cytoplasmic TDP-43 inclusions acquire distinct biophysical properties, recapitulate pathological hallmarks such as phosphorylation, ubiquitin, and p62 accumulation, and recruit nuclear endogenous TDP-43, leading to its loss of function. A transcriptomic signature linked to both aggregation and nuclear loss of TDP-43, including disease-specific cryptic splicing, is identified. Cytoplasmic TDP-43 aggregates exhibit time-dependent heterogeneous morphologies as observed in patients-including compacted, filamentous, or fragmented-which involve upregulation/recruitment of protein clearance pathways. Ultimately, cell-specific progressive toxicity is provoked by seeded TDP-43 pathology in human neurons. These findings identify TDP-43-templated aggregation as a key mechanism driving both cytoplasmic gain of function and nuclear loss of function, offering a valuable approach to identify modifiers of sporadic TDP-43 proteinopathies.}, } @article {pmid40157355, year = {2025}, author = {Scialò, C and Zhong, W and Jagannath, S and Wilkins, O and Caredio, D and Hruska-Plochan, M and Lurati, F and Peter, M and De Cecco, E and Celauro, L and Aguzzi, A and Legname, G and Fratta, P and Polymenidou, M}, title = {Seeded aggregation of TDP-43 induces its loss of function and reveals early pathological signatures.}, journal = {Neuron}, volume = {113}, number = {10}, pages = {1614-1628.e11}, doi = {10.1016/j.neuron.2025.03.008}, pmid = {40157355}, issn = {1097-4199}, mesh = {Humans ; *DNA-Binding Proteins/metabolism/genetics ; *Amyotrophic Lateral Sclerosis/pathology/metabolism/genetics ; *Frontotemporal Dementia/pathology/metabolism/genetics ; *Protein Aggregation, Pathological/pathology/metabolism/genetics ; *Neurons/metabolism/pathology ; Inclusion Bodies/metabolism/pathology ; }, abstract = {Neurodegeneration in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) results from both gain of toxicity and loss of normal function of the RNA-binding protein TDP-43, but their mechanistic connection remains unclear. Increasing evidence suggests that TDP-43 aggregates act as self-templating seeds, propagating pathology through the central nervous system via a prion-like cascade. We developed a robust TDP-43-seeding platform for quantitative assessment of TDP-43 aggregate uptake, cell-to-cell spreading, and loss of function within living cells, while they progress toward pathology. We show that both patient-derived and recombinant TDP-43 pathological aggregates were abundantly internalized by human neuron-like cells, efficiently recruited endogenous TDP-43, and formed cytoplasmic inclusions reminiscent of ALS/FTD pathology. Combining a fluorescent reporter of TDP-43 function with RNA sequencing and proteomics, we demonstrated aberrant cryptic splicing and a loss-of-function profile resulting from TDP-43-templated aggregation. Our data highlight known and novel pathological signatures in the context of seed-induced TDP-43 loss of function.}, } @article {pmid40157354, year = {2025}, author = {Klickstein, JA and Johnson, MA and Antonoudiou, P and Maguire, J and Paulo, JA and Gygi, SP and Weihl, C and Raman, M}, title = {ALS-related p97 R155H mutation disrupts lysophagy in iPSC-derived motor neurons.}, journal = {Stem cell reports}, volume = {20}, number = {5}, pages = {102478}, doi = {10.1016/j.stemcr.2025.102478}, pmid = {40157354}, issn = {2213-6711}, support = {K12 GM133314/GM/NIGMS NIH HHS/United States ; R21 NS123631/NS/NINDS NIH HHS/United States ; }, } @article {pmid40156516, year = {2025}, author = {Gorgich, EA and Heidari, Z and Mahmoudzadeh-Sagheb, H and Rustamzadeh, A and Shabani, A and Amirzadeh, A and Haghi Ashtiani, B}, title = {Brain Metabolite Profiles are Associated with Selective Neuronal Vulnerability and Underlying Mechanisms in Amyotrophic Lateral Sclerosis.}, journal = {ACS chemical neuroscience}, volume = {16}, number = {8}, pages = {1469-1480}, doi = {10.1021/acschemneuro.4c00593}, pmid = {40156516}, issn = {1948-7193}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism/diagnostic imaging ; Male ; Female ; Middle Aged ; Case-Control Studies ; Aged ; *Motor Cortex/metabolism/diagnostic imaging ; *Brain/metabolism ; Disease Progression ; Proton Magnetic Resonance Spectroscopy ; Adult ; *Neurons/metabolism ; Magnetic Resonance Imaging ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a lethal neurological syndrome accompanied by selective degeneration of somatic motor neurons and neurochemistry alterations. Nevertheless, eye movement's nuclei are relatively spared from ALS damage. This survey was to probe metabolite changes in the primary motor cortex (PMC) and interstitial nucleus of Cajal (INC) of ALS patients using proton magnetic resonance spectroscopy ([1]H-MRS). In this case-control study, 20 patients with ALS and 20 healthy controls underwent 1.5 T MRI and multivoxel [1]H-MRS. [1]H-MRS spectra to determine metabolite profiles including tNAA, mIns, tCr, tCho, and also tNAA/tCr, tNAA/tCho, and mIns/tNAA metabolite ratios from the PMC and INC were quantified via a point resolved spectroscopy pulse (PRESS) sequence in two groups. Further, the associations between [1]H-MRS markers with forced vital capacity (FVC), ALS functional rating scale (ALSFRS-R), and disease progression rate (ΔFS) were investigated. In the PMC, tNAA and tNAA/tCr were significantly lower in ALS patients than the healthy controls, but mIns and mIns/tNAA were significantly greater in these patients (p < 0.05). In the INC, tCho and mIns concentrations, and mIns/tNAA ratio were significantly increased (p < 0.05) in ALS patients, while tNAA and tNAA/tCr ratio did not show significant discriminations between the two groups (p > 0.05). The PMC tNAA/Cr ratio is associated with ALSFRS-R (p = 0.001, r = 0.71), FVC (p = 0.03, r = 0.58), and ΔFS (p = 0.01, r = -0.33). The mIns/tNAA ratio in PMC is also associated with ΔFS (p = 0.02, r = 0.41). In the INC, tCho concentrations (p = 0.04, r = -0.54) and mIns/tNAA ratio (p = 0.02, r = -0.38) were negatively associated with ALSFRS-R and positively correlated with ΔFS (p = 0.01, r = 0.33) and (p = 0.001, r = 0.61), respectively. The study suggests that neurochemistry changes in ALS patients' brains are linked to selective neuronal vulnerability and the underlying pathophysiology of the disease.}, } @article {pmid40155688, year = {2025}, author = {Fan, X and Zeng, Y and Zhang, F and Xu, Y and Duan, Q and Long, S and Lin, Y and Wang, K and Jiang, L}, title = {Genetic effects of circulating hormone and proteome on amyotrophic lateral sclerosis identified by Mendelian randomization.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {10782}, pmid = {40155688}, issn = {2045-2322}, support = {82201242//National Natural Science Foundation of China/ ; 82470903//National Natural Science Foundation of China/ ; LY24C110001//Natural Science Foundation of Zhejiang Province/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/genetics/blood ; Humans ; *Mendelian Randomization Analysis ; *Proteome/genetics ; Testosterone/blood/genetics ; Biomarkers/blood ; Male ; Insulin-Like Growth Factor I/genetics/metabolism ; Risk Factors ; Polymorphism, Single Nucleotide ; Genetic Predisposition to Disease ; Proteomics ; Female ; *Hormones/blood/genetics ; }, abstract = {Altered circulating hormones in ALS patients have been widely reported by previous observational studies, but whether these relationships are causal is unclear. Moreover, the potential therapeutic targets for ALS and the effects of plasma protein fluctuation on ALS progression are not fully understood. Therefore, we conducted a Mendelian randomization (MR) study to evaluate the causal role of 5 hormonal risk factors (insulin-like growth factor-1, IGF-1; sex hormone-binding globulin, SHBG; free testosterone, FT; total testosterone, TT; and estradiol) in ALS risk. Furthermore, we screened up to 90 circulating proteins including cytokines, chemokines, growth factors, and interferons, to identify potential therapeutic targets for ALS. Our MR analysis found genetically predicted higher level of FT was associated with a 23% lowered risk of ALS. Further screening of proteomic traits found that 12 plasma proteins were causally associated with ALS. These findings suggest that higher FT potentially exerts a protective effect on ALS risk. Several proteins may act as potential circulating biomarkers and therapeutic targets for ALS. In the future, high-throughput proteomic analyses and experimental explorations are likely needed to clarify the regulated role and mechanistic pathways.}, } @article {pmid40155564, year = {2025}, author = {Tang, J and Zhao, Y and Chen, Y and Yang, Y and Gong, Z and Li, Z and Zhang, M and Zhang, J}, title = {White matter integrity mediated the effect of plasma uric acid levels on cognitive function in ALS patients.}, journal = {Brain imaging and behavior}, volume = {19}, number = {3}, pages = {678-689}, pmid = {40155564}, issn = {1931-7565}, support = {82271478//National Natural Science Foundation of China/ ; 2024AOXIANG05//the Research and Innovation Team Project for Scientific Breakthroughs at Shanxi Bethune Hospital/ ; }, mesh = {Humans ; *Uric Acid/blood ; *White Matter/diagnostic imaging/pathology ; *Amyotrophic Lateral Sclerosis/blood/diagnostic imaging/physiopathology/psychology ; Male ; Female ; Middle Aged ; Diffusion Tensor Imaging/methods ; *Cognition/physiology ; Aged ; Brain/diagnostic imaging ; Executive Function/physiology ; Adult ; Neuropsychological Tests ; }, abstract = {OBJECTIVE: To investigate the association between plasma uric acid levels and white matter microstructural alterations in amyotrophic lateral sclerosis (ALS) patients and to explore the potential mediating role of white matter microstructural alterations in the protective effect of plasma uric acid on cognitive function in ALS patients.

METHODS: 73 right-handed ALS patients were recruited for this study. Plasma uric acid levels were measured, diffusion tensor imaging scans were performed to assess white matter integrity, and cognition was evaluated using the Edinburgh Cognitive and Behavioral Screen. The relationships among plasma uric acid, white matter integrity, and cognitive function were examined through multivariate linear regression analysis. Additionally, mediation analysis was performed to investigate whether white matter integrity mediated the relationship between uric acid levels and cognitive function.

RESULTS: The findings revealed a positive correlation between plasma uric acid levels and extensive preservation of white matter microstructure in various regions, including the fornix, cerebellar, internal capsule, frontotemporal and frontooccipital lobe bundles among ALS patients. Mediation analysis indicated that fractional anisotropy in the hippocampal portion of the cingulum fully mediated the effects of plasma uric acid levels on executive function in ALS patients.

INTERPRETATION: Our results suggested that elevated plasma uric acid may preserve the integrity of white matter microstructure in ALS patients. Furthermore, we have identified evidence supporting the mediating influence of the hippocampal portion of the cingulum in linking plasma uric acid levels to cognitive function among ALS patients.}, } @article {pmid40153582, year = {2024}, author = {Norata, D and Capone, F and Motolese, F and Marano, M and Rossi, M and Calandrelli, R and Sacchetti, M and Mantelli, F and Di Lazzaro, V and Pilato, F}, title = {1953-2023. Seventy Years of the Nerve Growth Factor: A Potential Novel Treatment in Neurological Diseases?.}, journal = {Aging and disease}, volume = {16}, number = {4}, pages = {2293-2314}, pmid = {40153582}, issn = {2152-5250}, mesh = {Humans ; *Nerve Growth Factor/therapeutic use ; Animals ; *Nervous System Diseases/therapy/drug therapy ; History, 20th Century ; History, 21st Century ; }, abstract = {Rita Levi-Montalcini's 1953 discovery of nerve growth factor (NGF) in mouse sarcoma tumors marked a groundbreaking moment in neuroscience. NGF, a key signaling molecule, became the first identified neurotrophic factor, influencing the growth, differentiation, and survival of neurons in both peripheral and central nervous systems. NGF and related neurotrophic factors hold therapeutic potential for various neurological disorders, such as Alzheimer's Disease, Parkinson's Disease, Huntington's Disease, amyotrophic lateral sclerosis, spinal cord injuries, neuropathies, traumatic brain injuries, and stroke. However, despite promising in vitro studies and animal models findings, NGF efficacy in patients remains unproven. Indeed, its use as a therapeutic agent faces challenges in delivery and clinical translation. This review delves into these challenges, exploring ongoing research on refined delivery methods, dosages, and safety profiles. Innovative strategies, including molecular mimicking, combination therapies, gene therapy, and coupling with neuromodulation techniques like transcranial magnetic stimulation and vagal nerve stimulation, are discussed. Incorporating nerve growth factor (NGF) into a comprehensive strategy may prove beneficial, particularly in non-neurodegenerative conditions such as stroke, trauma, and neuropathies. In these instances, NGF holds promise for promoting tissue regeneration and repair. Challenges persist in addressing the complexity of neurodegenerative pathologies for a combined therapeutic approach.}, } @article {pmid40152938, year = {2025}, author = {Yu, L and Yang, Z and Ming, Z and Zhou, Q and Zeng, S}, title = {Impaired Aortic Biomechanical Properties in Patients With Severe Obstructive Sleep Apnea Syndrome.}, journal = {Echocardiography (Mount Kisco, N.Y.)}, volume = {42}, number = {4}, pages = {e70135}, doi = {10.1111/echo.70135}, pmid = {40152938}, issn = {1540-8175}, support = {kq2208343//Natural Science Foundation of Changsha City/ ; 2024JJ8122//Natural Science Foundation of Hunan Province/ ; }, mesh = {Humans ; *Sleep Apnea, Obstructive/physiopathology/complications/diagnostic imaging ; Male ; Female ; Middle Aged ; *Aorta/physiopathology/diagnostic imaging ; Biomechanical Phenomena ; *Echocardiography/methods ; Adult ; Severity of Illness Index ; }, abstract = {PURPOSE: Evaluating the biomechanical properties of the aorta is crucial for assessing cardiovascular risk and preventing disease progression. The aim of this study was to evaluate the biomechanical properties of the ascending aorta (AA) in severe obstructive sleep apnea syndrome (OSAS) patients with or without hypertension (HT) via velocity vector imaging (VVI).

METHODS: A total of 68 patients with severe OSAS were selected, 35 of whom were included in the simple OSAS group and 33 of whom were included in the OSAS + HT group, and 40 volunteers without these two disorders who were taken as the control group. AA biomechanical properties, that is, AA longitudinal strain (ALS), AA circumferential strain (ACS), and fractional area change (FAC), were evaluated via VVI. Pulsed Doppler early transmitral peak flow velocity (E), early diastolic mitral annular velocity (e'), left ventricular (LV) global longitudinal strain (GLS), and the AA dimension (AD) were also measured.

RESULTS: ALS (mean ± SD; 32.8% ± 11.9% and 19.7% ± 7.6% vs. 40.6% ± 15.6%, p = 0.006), ACS (mean ± SD; 11.8% ± 3.5% and 8.6% ± 2.7% vs. 16.5% ± 5.8%, p = 0.02), and FAC (mean ± SD; 21.0% ± 5.3% and 12.4% ± 3.8% vs. 32.8% ± 9.7%, p = 0.004) were significantly lower in the patient groups (OSAS and OSAS + HT, respectively) than in the control group. LV systolic and diastolic functions were also impaired in the patient groups. Compared with volunteers without OSAS and HT, these patients had a greater AD and E/e' ratio and a lower GLS (p < 0.01). The aortic biomechanical properties were strongly correlated with the LV function and sleep parameters.

CONCLUSION: AA biomechanical properties are impaired in patients with severe OSAS, especially those with HT. Impairments in these aortic biomechanical properties are associated with diminished LV function and abnormal sleep parameters. This discovery may help clinicians identify and manage potential cardiovascular risks in OSAS patients. Further large-scale longitudinal studies are needed to confirm the potential predictive value of aortic events (e.g., aortic aneurysm or dissection) in patients with OSAS.}, } @article {pmid40152605, year = {2025}, author = {Yuan, C and Dong, H and Wu, C and Liu, J and Wang, Z and Wang, X and Ren, H and Wang, Z and Lu, Q}, title = {EPG-5 regulates TGFB/TGF-β and WNT signalling by modulating retrograde endocytic trafficking.}, journal = {Autophagy}, volume = {21}, number = {9}, pages = {1995-2008}, doi = {10.1080/15548627.2025.2485420}, pmid = {40152605}, issn = {1554-8635}, abstract = {The Vici syndrome protein EPG5 acts as a tethering factor determining the fusion specificity of autophagosomes with late endosomes/lysosomes. Here we demonstrated that during C. elegans development, EPG-5 modulates SMA and MAB TGFB/TGF-β signaling in controlling body size and also WNT signaling in regulating cell migration. EPG-5 is required for retrograde trafficking of the TGFB receptor SMA-6 and WLS/Wntless homolog MIG-14. In epg-5 mutants, SMA-6 and MIG-14 are trapped within hybrid endosomal structures, which colocalize with SNX-1- and SNX-3-labeled vesicles, respectively. Basolateral recycling processes of transmembrane cargos H.s.TFR/hTfR and H.s.IL2RA/hTAC are also defective in epg-5 mutants. Depletion of EPG-5 causes defective RAB-5 and RAB-7, and RAB-5 and RAB-10 conversion, leading to the formation of these hybrid vesicles. The defects in endocytic trafficking and autophagy in epg-5 mutants are ameliorated by knocking down components of the HOPS complex. Our study demonstrates the intersection between the autophagy pathway and the endocytic pathway, providing insights into the pathogenesis of amyotrophic lateral sclerosis (ALS) and Vici syndrome.Abbreviations: ALM: anterior lateral microtubule; ATG: autophagy related; AVM: anterior ventral microtubule; CORVET: class C core vacuole/endosome tethering; DAF-4: abnormal dauer formation 4; DIC: differential interference contrast; EPG: ectopic PGL granules; EPG-5: ectopic P granules 5; GAP: GTPase activating protein; GFP: green fluorescent protein; HOPS: homotypic fusion and vacuole protein sorting; H.s.IL2RA/hTAC: human interleukin 2 receptor subunit alpha; H.s.TFR/hTfR: human transferrin receptor; L1/L4: the first/fourth larval; mCh: mCherry; MIG-14: abnormal cell migration 14; PLM: posterior lateral microtubule; PVM: posterior ventral microtubule; RAB: ras-related protein; RFP: red fluorescent protein; RME-1: receptor mediated endocytosis 1; SMA-6: small 6; SNARE: soluble N-ethylmaleimide-sensitive factor attachment protein receptor; SNX: sorting nexin; TBC-2: TBC1 (Tre-2/Bub2/Cdc16) domain family 2; TGFB/TGF-β: transforming growth factor beta; TGN: trans-Golgi network; VPS: related to yeast vacuolar protein sorting factor; WT: wild type.}, } @article {pmid40152389, year = {2025}, author = {Belosludtseva, NV and Ilzorkina, AI and Dubinin, MV and Mikheeva, IB and Belosludtsev, KN}, title = {Comparative Study of Structural and Functional Rearrangements in Skeletal Muscle Mitochondria of SOD1-G93A Transgenic Mice at Pre-, Early-, and Late-Symptomatic Stages of ALS Progression.}, journal = {Frontiers in bioscience (Landmark edition)}, volume = {30}, number = {3}, pages = {28260}, doi = {10.31083/FBL28260}, pmid = {40152389}, issn = {2768-6698}, support = {23-25-00286//Russian Science Foundation/ ; }, mesh = {Animals ; *Amyotrophic Lateral Sclerosis/pathology/physiopathology/genetics ; Mice, Transgenic ; Mice ; *Superoxide Dismutase/genetics/metabolism ; *Muscle, Skeletal/ultrastructure/pathology/metabolism/physiopathology ; *Mitochondria, Muscle/ultrastructure/metabolism/pathology ; Male ; Disease Progression ; Superoxide Dismutase-1 ; Disease Models, Animal ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive multisystem disease characterized by limb and trunk muscle weakness that is attributed, in part, to abnormalities in mitochondrial ultrastructure and impaired mitochondrial functions. This study investigated the time course of structural and functional rearrangements in skeletal muscle mitochondria in combination with motor impairments in Tg (copper-zinc superoxide dismutase enzyme (SOD1) G93A) dl1/GurJ (referred to as SOD1-G93A/low) male mice, a familial ALS model, as compared with non-transgenic littermates.

METHODS: The neurological status and motor functions were assessed weekly using the paw grip endurance method and the grid suspension test with two-limb and four-limb suspension tasks. Transmission electron microscopy followed by quantitative analysis was performed to study ultrastructural alterations in the quadriceps femoris. Functional analysis of skeletal muscle mitochondria was performed using high-resolution Oxygraph-2k (O2K) respirometry and methods for assessing the calcium retention capacity index and the content of lipid peroxidation products in freshly isolated preparations.

RESULTS: Based on the behavioral phenotyping data, specific age groups were identified: postnatal day 56 (P56) (n = 10-11), 84 (P84) (n = 10-11), and 156 (P154) (n = 10-12), representing the pre-symptomatic, early-symptomatic and late-symptomatic stages of ALS progression in SOD1-G93A/low mice, respectively. Electron microscopy showed mosaic destructive changes in subsarcolemmal mitochondria in fibers of the quadriceps femoris from 84-day-old SOD1-G93A/low mice. Morphometric analysis revealed an elevation in the mean size of the mitochondria in SOD1-G93A mice at P84 and P154. In addition, the P154 transgenic group demonstrated a decrease in sarcomere width and the number of mitochondria per unit area. At the symptomatic stage, SOD1-G93A mice exhibited a decreased respiratory control ratio, ADP-stimulated, and uncoupled respiration rates of mitochondria isolated from the quadriceps femoris muscle, as measured by high-resolution respirometry. In parallel, the mitochondria showed lower calcium retention capacity and increased levels of lipid peroxidation products compared with the control.

CONCLUSIONS: Taken together, these results indicate stage-dependent changes in skeletal muscle mitochondrial ultrastructure and functions associated with defective oxidative phosphorylation, impaired calcium homeostasis, and oxidative damage in the SOD1-G93A/low mouse model, which appears to be a promising direction for the development of combination therapies for ALS.}, } @article {pmid40151753, year = {2025}, author = {Carqueja, I and Montenegro Sá, F and Monteiro, S}, title = {Ventricular Arrhythmias Caused by Left Main Coronary Artery Vasospasm: A Diagnostic Challenge in a Cardiac Arrest Victim.}, journal = {Cureus}, volume = {17}, number = {2}, pages = {e79554}, pmid = {40151753}, issn = {2168-8184}, abstract = {Sudden cardiac death (SCD) is a common cause of cardiovascular deaths. It may be caused by primary electrical diseases, cardiomyopathies, myocarditis, valvular heart diseases, or coronary artery disease (including acute coronary syndrome). Coronary artery vasospasm is defined as a transient total or subtotal coronary artery obstruction, associated with angina symptoms and ischemic findings on electrocardiogram (ECG). It is a cause of myocardial infarction, life-threatening arrhythmias, atrioventricular block, and SCD. A 55-year-old man presented to the hospital after an out-of-hospital cardiac arrest (OHCA). He had a previous history of cardiovascular risk factors, excessive alcohol intake, non-obstructive coronary artery disease, and paroxysmic atrial fibrillation. On the day of the OHCA, he had a sudden collapse while exercising, with ventricular fibrillation and return of spontaneous circulation (ROSC) after advanced life support (ALS). No ECG or echocardiographic anomalies were identified on hospital admission. The patient suffered three more episodes of cardiac arrest during the hospital stay, with atypical arrhythmic presentations. No ECG or echocardiographic abnormalities were observed after ROSC. The fourth cardiac arrest had concomitant segmental ST changes and de novoechocardiographic segmental motility abnormalities suggestive of left main coronary artery occlusion. These findings were transient, with a normal ECG and echocardiogram obtained one hour after ROSC. No electrolyte abnormalities or other causes of cardiac arrest were identified. The hypothesis of left main coronary vasospasm was raised as the likely diagnosis. Coronary artery vasospasm is a possible cause of major cardiac events. Diagnosis can be challenging due to the transient findings and varied manifestations, often in patients with normal coronary arteries. The correct diagnosis and treatment of coronary artery vasospasm can have a determinant effect on prognosis and mortality, as appropriate treatment can lead to prolonged event-free survival. Provocative coronary vasospasm tests performed in patients with atypical cardiovascular manifestations can allow for the timely diagnosis of vasospasm and avoid critical events. The authors aim to raise awareness of the different clinical presentations of coronary artery vasospasm and its consequences. The performance of provocative tests in selected patients should be considered to promote early diagnosis and potentially avoid major events.}, } @article {pmid40151693, year = {2025}, author = {Tariq, D and Madhusudan, R and Guntupalli, Y and Karumanchi Anantha Venkata Sai, S and Vejandla, B and Lnu, M}, title = {A Cross-Sectional Study Comparing Patient Information Guides for Amyotrophic Lateral Sclerosis, Myasthenia Gravis, and Guillain-Barré Syndrome Produced by ChatGPT-4 and Google Gemini 1.5.}, journal = {Cureus}, volume = {17}, number = {2}, pages = {e79646}, pmid = {40151693}, issn = {2168-8184}, abstract = {INTRODUCTION: Patient education for amyotrophic lateral sclerosis (ALS), myasthenia gravis (MG), and Guillain-Barré syndrome (GBS) is essential for effective symptom management, improving quality of life, and enabling informed care decisions. AI tools enhance healthcare and patient education through personalized care and improved diagnostics.

METHODS:  In this study, ChatGPT (OpenAI, San Francisco, CA, USA) and Google Gemini (Mountain View, CA, USA) generated patient education guides for ALS, MG, and GBS. Variables included word count, sentence count, average words and syllables per sentence, grade level, ease score using the Flesch-Kincaid calculator, similarity score using QuillBot, and reliability using a modified DISCERN score. Statistical analysis was done using R version 4.3.2 (2023; R Foundation for Statistical Computing, Vienna, Austria).

RESULTS: ChatGPT-generated brochures for patient education on ALS, MG, and GBS had a higher grade level and lower ease score compared to those generated by Google Gemini. Although both models had similar reliability and similarity percentages, ChatGPT produced more content with greater complexity and slightly higher reliability.

CONCLUSION:  This study found no significant difference in the average ease, grade, and reliability scores between the two AI tools when generating patient information brochures on ALS, MG and GBS. However, a statistically significant difference was observed in the mean word counts generated by the tools.}, } @article {pmid40151398, year = {2025}, author = {Roy, SM and Acquarone, E and Argyrousi, EK and Zhang, H and Staniszewski, A and Inoue, A and Ziarek, JJ and Arancio, O and Watterson, DM}, title = {Optimized 5-HT2b inhibitors for neuropsychiatric syndromes with cognitive dysfunction.}, journal = {Alzheimer's & dementia (New York, N. Y.)}, volume = {11}, number = {1}, pages = {e70073}, pmid = {40151398}, issn = {2352-8737}, abstract = {INTRODUCTION: Neuropsychiatric syndromes such as anxiety and agitation are clinical presentations common to diverse neurodegenerative diseases and brain injury sequelae. They are a concern due to the impact on cognition, social interactions, and non-pharmacological treatments. Cognitive or behavioral disturbances occur at early disease stages and increase with disease progression. Coincident pathologies include the loss of serotonin (5-HT) neurons and appearance of neurofibrillary tangles in the raphe nucleus. Brain 5-HT2b receptor (5-HT2bR) levels are increased in Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), and post-stroke morbidity. HTR2B gene variants are implicated in psychiatric disorders. 5-HTRs are associated with atypical neurotropic drug mechanisms and behavioral dysfunction in drug abuse. The accumulating body of evidence suggests that selective 5-HT2bR inhibition might mitigate neuropsychiatric syndromes and the associated cognitive dysfunction. Atypical neurotropic drugs interact with a variety of monoamine receptors and outcomes are viewed as a combination of 5-HT and dopamine D2 receptor mediated actions. Clearly, there is a need for insight into precision 5-HT2bR inhibition as a potential pharmacological mechanism for treatment of neuropsychiatric syndromes and cognitive dysfunction associated with dementia.

METHODS: Strategic optimization of an atypical neurotropic drug was used to develop MW073, a highly selective and orally bioavailable inhibitor of 5-HT2bR activity and β-arrestin-1 recruitment that is devoid of dopamine receptor recognition and risk of 5-HT2bR agonist activity.

RESULTS: MW073 ameliorates amyloid and tau induction of behavioral dysfunction in preventive or disease stage intervention paradigms. Using MW073 as a standard of comparison, risperidone was shown to be a dose-dependent inhibitor 5-HT2bR activity and β-arrestin-1 recruitment.

DISCUSSION: Selective inhibition of 5-HT2bR activity is a viable mechanism for the treatment of neuropsychiatric syndromes with synaptic dysfunction as a root cause and is a previously unrealized pharmacodynamic mechanism potentially embedded in current neurotherapeutics.

HIGHLIGHTS: A new highly selective 5-HT2bR antagonist, MW073, is described and used as a reference standard.MW073 attenuates synaptic and behavioral dysfunctions an animal models of neuropsychatric syndromes.Risperidone is a dose dependent inhibitor of 5-HT2bR activity and arrestin recruitment.}, } @article {pmid40150989, year = {2025}, author = {Matsumoto, S and Tateishi-Karimata, H and Ohyama, T and Sugimoto, N}, title = {Controlling the Local Conformation of RNA G-Quadruplex Results in Reduced RNA/Peptide Cytotoxic Accumulation Associated with C9orf72 ALS/FTD.}, journal = {Small methods}, volume = {9}, number = {6}, pages = {e2401630}, doi = {10.1002/smtd.202401630}, pmid = {40150989}, issn = {2366-9608}, mesh = {*G-Quadruplexes/drug effects ; Humans ; *C9orf72 Protein/genetics/metabolism ; *Amyotrophic Lateral Sclerosis/genetics/metabolism ; *RNA/chemistry/metabolism/genetics ; *Peptides/metabolism/chemistry ; *Frontotemporal Dementia/genetics/metabolism ; Cell Line, Tumor ; DNA Repeat Expansion ; Nucleic Acid Conformation ; }, abstract = {Repeat expansion of d(G4C2) in the noncoding region of the C9orf72 gene contributes to neurodegenerative diseases. The repeat expansion transcript r(G4C2) induces RNA/peptide accumulation, which, in turn, induces cytotoxicity and accelerates the development of neurodegenerative diseases. Such cytotoxic accumulation is triggered by peptide aggregation. Here, a technique is developed to prevent accumulation by regulating RNA interactions, assuming that RNA structure is important for peptide interactions. A screening method is used to identify compounds that suppress RNA accumulation of r(G4C2) repeats. The four compounds are identified with wide π-planes containing hydroxyl, methoxy, and cyclic ether groups that suppressed RNA accumulation. Interestingly, these compounds also suppressed RNA/peptide accumulation in neuroblastoma cells, indicating that RNA accumulation is a key regulator of RNA/peptide cytotoxic aggregate formation. In vitro and in silico physicochemical analyses reveal that these compounds bind to the loop region of the G-quadruplex via hydrogen bonds or CH-π interactions, resulting in an altered loop conformation. Importantly, these conformational changes inhibited RNA G-quadruplex associations. These results show that conformational changes are promising for controlling the interactions between G-quadruplexes and further RNA accumulation. These findings may be useful in the development of therapeutic strategies for the treatment of neurodegenerative diseases.}, } @article {pmid40149779, year = {2025}, author = {Ginanneschi, F and Casali, S and Cioni, C and Righi, D and Emmanuello, E and Toccaceli, C and Plantone, D and De Stefano, N}, title = {Does Lumbar Puncture Still Have Clinical Value for Patients with Amyotrophic Lateral Sclerosis?.}, journal = {Brain sciences}, volume = {15}, number = {3}, pages = {}, pmid = {40149779}, issn = {2076-3425}, abstract = {Background: The relationship between routine cerebrospinal fluid (CSF) testing and clinical and prognostic data in amyotrophic lateral sclerosis (ALS) remains unclear. Additionally, biochemical data have never been correlated with markers of neurodegeneration. The purpose of this study is to determine whether lumbar puncture may still have clinical utility in ALS. Methods: We collected the CSF profiles of 140 ALS subjects. CSF protein, albumin, IgG, IgG index, albumin quotient (QAlb), t-tau, p-tau, and Aβ42 were analyzed. Results: Approximately one-quarter of ALS patients had elevated levels of protein, albumin, and QAlb in the CSF, but these were not associated with clinical or survival data. Among the neurodegeneration markers, the percentage of patients with abnormal values ranged from 26.3% to 35.4%. The p-tau/t-tau ratio and Aβ42 were correlated with both the ALS progression rate and the time from diagnosis to death. Aβ42 was the prognostic marker most strongly associated with survival. Conclusions: The lack of correlation between biochemical CSF findings and the clinical and/or prognostic status of ALS suggests that these markers have no clinical value. However, neurodegeneration markers that are easily measurable in clinical laboratories, particularly Aβ42, may be useful at the time of diagnosis for predicting ALS survival and progression rate.}, } @article {pmid40149599, year = {2025}, author = {Yang, W and Xiao, W and Liu, X and Li, H and Huang, T and Fan, D}, title = {Testosterone Supplementation: A Potential Therapeutic Strategy for Amyotrophic Lateral Sclerosis.}, journal = {Biomedicines}, volume = {13}, number = {3}, pages = {}, pmid = {40149599}, issn = {2227-9059}, support = {82071426//National Natural Science Foundation of China/ ; }, abstract = {Objectives: Amyotrophic lateral sclerosis (ALS) is a progressive and fatal disease characterized by the degeneration of spinal cord and brain neurons. Proteomics combined with Mendelian randomization (MR) is an effective method for finding disease treatment targets. Methods: We aimed to seek new therapeutic targets for ALS. A large-scale GWAS on proteomics (4907 circulatory protein) with 35,559 individuals was included as the exposure data; a GWAS with 138,086 ALS patients was used as the outcome data; we found that a high level of sex hormone-binding globulin (SHBG) is a risk factor by MR analysis. Colocalization analyses were used to validate the causality between SHBG and ALS further. Functional enrichment found a high level of SHBG was associated with a low level of bioavailable testosterone. Two-sample MR confirmed the association of SHBG (400,210 samples), bioavailable testosterone (367,289 samples), and ALS. Results: A high level of SHBG, and a low level of bioavailable testosterone are risk factors for ALS. Conclusions: A low level of bioavailable testosterone is a risk factor for ALS. Although our study is relatively limited and cannot fully confirm that testosterone supplementation has a therapeutic effect on ALS, it offers a promising direction for ALS therapy.}, } @article {pmid40149536, year = {2025}, author = {Kleinerova, J and Chipika, RH and Tan, EL and Yunusova, Y and Marchand-Pauvert, V and Kassubek, J and Pradat, PF and Bede, P}, title = {Sensory Dysfunction in ALS and Other Motor Neuron Diseases: Clinical Relevance, Histopathology, Neurophysiology, and Insights from Neuroimaging.}, journal = {Biomedicines}, volume = {13}, number = {3}, pages = {}, pmid = {40149536}, issn = {2227-9059}, support = {JPND-Cofund-2-2019-1 & HRB EIA-2017-019//HRB/ ; }, abstract = {Background: The clinical profiles of MNDs are dominated by inexorable motor decline, but subclinical proprioceptive, nociceptive and somatosensory deficits may also exacerbate mobility, dexterity, and bulbar function. While extra-motor pathology and frontotemporal involvement are widely recognised in motor neuron diseases (MNDs), reports of sensory involvement are conflicting. The potential contribution of sensory deficits to clinical disability is not firmly established and the spectrum of sensory manifestations is poorly characterised. Methods: A systematic review was conducted to examine the clinical, neuroimaging, electrophysiology and neuropathology evidence for sensory dysfunction in MND phenotypes. Results: In ALS, paraesthesia, pain, proprioceptive deficits and taste alterations are sporadically reported and there is also compelling electrophysiological, histological and imaging evidence of sensory network alterations. Gait impairment, impaired dexterity, and poor balance in ALS are likely to be multifactorial, with extrapyramidal, cerebellar, proprioceptive and vestibular deficits at play. Human imaging studies and animal models also confirm dorsal column-medial lemniscus pathway involvement as part of the disease process. Sensory symptoms are relatively common in spinal and bulbar muscular atrophy (SBMA) and Hereditary Spastic Paraplegia (HSP), but are inconsistently reported in primary lateral sclerosis (PLS) and in post-poliomyelitis syndrome (PPS). Conclusions: Establishing the prevalence and nature of sensory dysfunction across the spectrum of MNDs has a dual clinical and academic relevance. From a clinical perspective, subtle sensory deficits are likely to impact the disability profile and care needs of patients with MND. From an academic standpoint, sensory networks may be ideally suited to evaluate propagation patterns and the involvement of subcortical grey matter structures. Our review suggests that sensory dysfunction is an important albeit under-recognised facet of MND.}, } @article {pmid40149460, year = {2025}, author = {Ghezzi, A and Gianferrari, G and Baldassarri, E and Zucchi, E and Martinelli, I and Vacchiano, V and Bonan, L and Zinno, L and Nuredini, A and Canali, E and Gizzi, M and Terlizzi, E and Medici, D and Sette, E and Currò Dossi, M and Morresi, S and Santangelo, M and Patuelli, A and Longoni, M and De Massis, P and Ferro, S and Fini, N and Simonini, C and Carra, S and Zamboni, G and Mandrioli, J}, title = {Phenotypical Characterization of C9ALS Patients from the Emilia Romagna Registry of ALS: A Retrospective Case-Control Study.}, journal = {Genes}, volume = {16}, number = {3}, pages = {}, pmid = {40149460}, issn = {2073-4425}, support = {00000000//Emilia Romagna Regional Health Authority/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/pathology/epidemiology ; Male ; Female ; Middle Aged ; *C9orf72 Protein/genetics ; Registries ; Aged ; Case-Control Studies ; Phenotype ; Retrospective Studies ; Disease Progression ; Adult ; Prognosis ; Italy/epidemiology ; }, abstract = {BACKGROUND/OBJECTIVES: C9ORF72 expansion is associated with significant phenotypic heterogeneity. This study aimed to characterize the clinical features of C9ALS patients from the Emilia Romagna ALS registry (ERRALS) and compare them with non-mutated ALS (nmALS) patients matched for sex, age at onset, and diagnostic delay, sourced from the same register.

METHODS: In total, 67 C9ALS patients were compared to 201 nmALS. Clinical data, phenotype, and prognostic factors were analyzed in the two groups and within the C9ALS group after stratification by sex.

RESULTS: C9ALS patients displayed a higher disease progression rate and shorter times to gastrostomy and invasive ventilation, despite no differences in overall survival. Female C9ALS had a more severe bulbar and upper motor neuron involvement compared to males. Cognitive and behavioral symptoms were more common in the C9ALS group, and the former was an independent prognostic factor. Prevalences of, autoimmune diseases, and dyslipidemia were significantly higher among C9ALS patients.

CONCLUSIONS: In our dataset, we show an overall increased disease progression rate in C9ALS patients and hint at sex-specific discrepancies in some phenotypical characteristics. We also suggest a possible clinically relevant involvement of C9ORF72 expansion in metabolism and autoimmunity.}, } @article {pmid40149017, year = {2025}, author = {Suk, TR and Part, CE and Zhang, JL and Nguyen, TT and Heer, MM and Caballero-Gómez, A and Grybas, VS and McKeever, PM and Nguyen, B and Ali, T and Callaghan, SM and Woulfe, JM and Robertson, J and Rousseaux, MWC}, title = {A stress-dependent TDP-43 SUMOylation program preserves neuronal function.}, journal = {Molecular neurodegeneration}, volume = {20}, number = {1}, pages = {38}, pmid = {40149017}, issn = {1750-1326}, support = {PJT-195691//CIHR/ ; }, mesh = {*Sumoylation/physiology ; Humans ; *DNA-Binding Proteins/metabolism/genetics ; Animals ; *Neurons/metabolism ; Mice ; Amyotrophic Lateral Sclerosis/metabolism ; Male ; Frontotemporal Dementia/metabolism ; Female ; Aging/metabolism ; *Stress, Physiological/physiology ; TDP-43 Proteinopathies/metabolism ; }, abstract = {Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD) are overwhelmingly linked to TDP-43 dysfunction. Mutations in TDP-43 are rare, indicating that the progressive accumulation of exogenous factors - such as cellular stressors - converge on TDP-43 to play a key role in disease pathogenesis. Post translational modifications such as SUMOylation play essential roles in response to such exogenous stressors. We therefore set out to understand how SUMOylation may regulate TDP-43 in health and disease. We find that TDP-43 is regulated dynamically via SUMOylation in response to cellular stressors. When this process is blocked in vivo, we note age-dependent TDP-43 pathology and sex-specific behavioral deficits linking TDP-43 SUMOylation with aging and disease. We further find that SUMOylation is correlated with human aging and disease states. Collectively, this work presents TDP-43 SUMOylation as an early physiological response to cellular stress, disruption of which may confer a risk for TDP-43 proteinopathy.}, } @article {pmid40148124, year = {2025}, author = {Beckers, D and Kretz, F and Glandorf, K and Abdassalam, S and Amer, M and Breyer, DRH and Kaymak, H and Klabe, K and Beckers, L}, title = {Automated Comprehensive Analysis of Preoperative Biometric Parameters in Cataract Patients: A Retrospective Study of over 6000 Eyes.}, journal = {Klinische Monatsblatter fur Augenheilkunde}, volume = {242}, number = {5}, pages = {555-561}, doi = {10.1055/a-2541-4942}, pmid = {40148124}, issn = {1439-3999}, mesh = {Humans ; Female ; Male ; Retrospective Studies ; *Biometry/methods ; *Cataract/epidemiology/diagnosis/pathology ; Aged ; Middle Aged ; *Cataract Extraction/statistics & numerical data ; Germany/epidemiology ; Aged, 80 and over ; *Preoperative Care/statistics & numerical data/methods ; Reproducibility of Results ; Sensitivity and Specificity ; Adult ; }, abstract = {Cataract surgery is one of the most successful surgical procedures, improving vision and quality of life for millions globally. An accurate preoperative measurement is crucial for predicting outcomes, particularly in minimizing postoperative refractive errors through precise intraocular lens (IOL) selection. This study aimed to analyze preoperative biometric data in cataract patients to identify key parameters relevant for clinical decision-making. The study also sought to understand patient demographics and biometrics in a representative population. An automated retrospective analysis was conducted on the preoperative biometric data of 6 163 eyes from 3 118 patients who underwent cataract or clear lens extraction (CLE) surgery in a German clinic over the past 2 years. All measurements were taken using the IOL Master 700 (Carl Zeiss Meditec, Jena, Germany), and data were automatically transferred for analysis using a dedicated software tool. Biometric parameters assessed included axial length (AL), keratometry values (K, TK), anterior chamber depth (ACD), lens thickness (LT), and vitreous length (VL). The age and gender distribution of the cohort was also considered. The biometric data from this large patient cohort largely aligns with published norms for cataract patients. The majority of eyes exhibited ALs and corneal curvatures within expected ranges, supporting accurate IOL power calculations. The study also confirmed a high prevalence of mild astigmatism, suggesting that toric IOLs could address residual astigmatism for better visual outcomes. This study's large sample size adds valuable insights into preoperative cataract patient data and shows the value of an automated analysis.}, } @article {pmid40148057, year = {2025}, author = {De Marchi, F and Spinelli, EG and Bendotti, C}, title = {Neuroglia in neurodegeneration: Amyotrophic lateral sclerosis and frontotemporal dementia.}, journal = {Handbook of clinical neurology}, volume = {210}, number = {}, pages = {45-67}, doi = {10.1016/B978-0-443-19102-2.00004-1}, pmid = {40148057}, issn = {0072-9752}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/pathology ; *Frontotemporal Dementia/pathology ; *Neuroglia/pathology/metabolism ; Animals ; }, abstract = {Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are devastating neurodegenerative diseases sharing significant pathologic and genetic overlap, leading to consider these diseases as a continuum in the spectrum of their pathologic features. Although FTD compromises only specific brain districts, while ALS involves both the nervous system and the skeletal muscles, several neurocentric mechanisms are in common between ALS and FTD. Also, recent research has revealed the significant involvement of nonneuronal cells, particularly glial cells such as astrocytes, oligodendrocytes, microglia, and peripheral immune cells, in disease pathology. This chapter aims to provide an extensive overview of the current understanding of the role of glia in the onset and advancement of ALS and FTD, highlighting the recent implications in terms of prognosis and future treatment options.}, } @article {pmid40147067, year = {2025}, author = {Jiang, T and Ding, W and Li, X}, title = {Serum creatine kinase dynamics in amyotrophic lateral sclerosis: Predictive role of male sex, limb onset, and intermediate disease duration for stratified monitoring.}, journal = {Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia}, volume = {135}, number = {}, pages = {111203}, doi = {10.1016/j.jocn.2025.111203}, pmid = {40147067}, issn = {1532-2653}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/blood/diagnosis ; Male ; *Creatine Kinase/blood ; Female ; Middle Aged ; Retrospective Studies ; Aged ; Biomarkers/blood ; Adult ; Disease Progression ; Sex Factors ; }, abstract = {OBJECTIVE: To investigate serum creatine kinase (CK) levels in amyotrophic lateral sclerosis (ALS) patients and their associations with disease characteristics, exploring its utility as a biomarker for disease progression.

METHODS: This retrospective study included 81 definitive ALS patients and 99 matched controls. Serum CK levels were analyzed against sex, age, onset site, disease duration, and ALSFRS-R scores using Mann-Whitney U tests, Kruskal-Wallis tests, and multivariate regression.

RESULTS: ALS patients exhibited significantly elevated CK levels compared to controls (233.92 ± 216.91 vs. 101.81 ± 34.28 IU/L, P < 0.05), with 65.43 % exceeding gender-specific ranges. Multivariate analysis identified male sex (β = 0.32, 95 % CI: 0.21-0.43; P < 0.05), limb onset (vs. bulbar: β = 0.41, 95 % CI: 0.29-0.53; P < 0.05), and intermediate disease duration (1-3 years: β = 0.32, P < 0.05) as independent predictors. CK levels peaked in limb-onset patients (lower limb: 342.40 ± 283.53 IU/L vs. bulbar: 96.20 ± 49.39 IU/L; P < 0.05). Higher CK was associated with moderate disease severity (ALSFRS-R 36-40 vs. ≤ 35: P < 0.05).

CONCLUSION: Serum CK elevation in ALS is strongly linked to male sex, limb onset, and intermediate disease duration (1-3 years), though long-duration cases (>3 years) were underrepresented (n = 4). These findings highlight CK's potential as a cost-effective biomarker for personalized monitoring, particularly in limb-onset males with moderate functional impairment. Further validation in larger cohorts is warranted.}, } @article {pmid40145977, year = {2026}, author = {Zhao, W and Liu, Z and Wu, J and Liu, A and Yan, J}, title = {Potential targets of microglia in the treatment of neurodegenerative diseases: Mechanism and therapeutic implications.}, journal = {Neural regeneration research}, volume = {21}, number = {4}, pages = {1497-1511}, doi = {10.4103/NRR.NRR-D-24-01343}, pmid = {40145977}, issn = {1673-5374}, abstract = {For diverse neurodegenerative disorders, microglial cells are activated. Furthermore, dysfunctional and hyperactivated microglia initiate mitochondrial autophagy, oxidative stress, and pathological protein accumulation, ending with neuroinflammation that exacerbates damage to dopaminergic neurons and contributes significantly to the pathology of neurodegenerative disorder. Microglial over-activation is closely associated with the secretion of pro-inflammatory cytokines, the phagocytosis of injured neurons, and the modulation of neurotoxic environments. This review summarizes the role of microglia neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, multiple sclerosis, multiple system atrophy, amyotrophic lateral sclerosis, frontotemporal dementia, progressive supranuclear palsy, cortical degeneration, Lewy body dementia, and Huntington's disease. It also discusses novel forms of cell death such as ferroptosis, cuproptosis, disulfidptosis, and parthanatos (poly(adenosine diphosphate ribose) polymerase 1-dependent cell death), as well as the impact of regulatory factors related to microglial inflammation on microglial activation and neuroinflammation. The aim is to identify potential targets for microglial cell therapy in neurodegenerative diseases.}, } @article {pmid40145976, year = {2025}, author = {Wang, Z and Cao, W and Chen, L and Zhang, S and Tang, L and Cui, W and Kong, M and Yu, L and Fan, D and Zheng, W}, title = {The role of the peripheral immune system in mediating axonal dysfunction in early-stage amyotrophic lateral sclerosis: an age- and sex-based analysis.}, journal = {Neural regeneration research}, volume = {}, number = {}, pages = {}, doi = {10.4103/NRR.NRR-D-24-01081}, pmid = {40145976}, issn = {1673-5374}, abstract = {Amyotrophic lateral sclerosis is characterized by the progressive loss of motor neurons. Early-stage axonal dysfunction, rather than central nervous system injury, plays a key role in the disease process. However, the molecular mechanisms underlying this dysfunction remain unclear. To investigate the relationship between peripheral immune dysregulation and axonal dysfunction in amyotrophic lateral sclerosis, we recruited 372 patients within the first 12 months of sporadic amyotrophic lateral sclerosis onset between January 2018 and May 2024. We collected peripheral immune markers at baseline, including total leukocytes, lymphocytes, monocytes, neutrophils, basophils, eosinophils, and platelets. We also calculated four derived ratios: neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, and systemic immune inflammation index. Multivariate analysis, adjusted for confounding factors, revealed that higher counts of total leukocytes and neutrophils, as well as higher neutrophil-related ratios, including the neutrophil to lymphocyte ratio and the systemic immune inflammation index, were significantly correlated with higher compound muscle action potential scores. Stratified analyses revealed that these associations varied by age and sex. Furthermore, mediation analysis demonstrated that axonal dysfunction plays a significant role in the relationship between immune markers and disease progression. These findings emphasize the critical role that peripheral immune dysregulation plays in amyotrophic lateral sclerosis progression by mediating peripheral nerve injury, particularly in the early stages of the disease. This study highlights the importance of the peripheral nervous system in the early stages of amyotrophic lateral sclerosis and provides new insights into disease mechanisms and potential therapeutic targets.}, } @article {pmid40143847, year = {2025}, author = {Meyer, J and Gaur, N and von der Gablentz, J and Friedrich, B and Roediger, A and Grosskreutz, J and Steinbach, R}, title = {Phosphorylated neurofilament heavy chain (pNfH) concentration in cerebrospinal fluid predicts overall disease aggressiveness (D50) in amyotrophic lateral sclerosis.}, journal = {Frontiers in neuroscience}, volume = {19}, number = {}, pages = {1536818}, pmid = {40143847}, issn = {1662-4548}, abstract = {INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder, characterized by tremendous clinical heterogeneity that necessitates reliable biomarkers for the trajectory of the disease. The potential of phosphorylated Neurofilament-Heavy-chain (pNfH) measured in cerebrospinal fluid (CSF) to mirror disease progressiveness has repeatedly been suggested but is not applicable as outcome on an individual patient-level. This potential was probably obfuscated before due to imprecise clinical measures of disease progression that assumed a linear decline of motoric function over time. The primary objective was therefore to study if disease aggressiveness, as quantified via the D50 model, would reveal more stable correlations with pNfH.

METHODS: ELISA-quantified pNfH CSF levels of 108 patients with ALS were comparatively analyzed in relation to three different measures of disease progression speed via analyses of covariance, linear and non-linear regressions, respectively. These were (a) the D50, depicting a patient's overall disease aggressiveness, (b) cFL, the calculated functional loss-rate as locally derived parameter of progression speed, and (c) DPR, the disease progression-rate as more commonly used linear approximation of points lost per month in the ALS functional rating scale since symptom onset.

RESULTS: All analyses of covariance showed a significant main impact of the respective disease progression-speed parameter on pNfH, independent of disease phase, presence of frontotemporal dementia, analyzing laboratory, sex or clinical onset type, while only age revealed borderline additional influence. Notably, CSF pNfH concentration was independent of how far the disease had progressed, as neither disease phase nor a direct regression with the quantified disease accumulation at the time of lumbar puncture revealed a significant correlation. However, the parameter D50 quantifying aggressiveness showed the most significant impact on pNfH-levels, as compared to the cFL and even more evident in contrast to the DPR. This superiority of D50 was confirmed in direct linear and most evident in non-linear regressions with pNfH.

CONCLUSION: Overall disease aggressiveness in ALS, as quantified by D50, most robustly correlated with CSF pNfH-levels, independent of the time of collection during symptomatic disease. This opens perspectives to use CSF pNfH as a prognostic outcome measure for future therapeutic interventions in the sense of precision medicine.}, } @article {pmid40143800, year = {2025}, author = {Heylen, A and Vermeiren, Y and De Deyn, PP and Van Dam, D}, title = {Monoaminergic Alterations at the Subregional Cervical and Thoracic Spinal Cord Level of Patients Within the FTD-ALS Continuum and Early-Onset AD: Low Thoracic Dopaminergic Activity in ALS.}, journal = {Journal of neurochemistry}, volume = {169}, number = {3}, pages = {e70046}, doi = {10.1111/jnc.70046}, pmid = {40143800}, issn = {1471-4159}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism/pathology ; Female ; Male ; *Frontotemporal Dementia/metabolism ; Aged ; Middle Aged ; *Dopamine/metabolism ; *Spinal Cord/metabolism ; *Alzheimer Disease/metabolism ; *Biogenic Monoamines/metabolism ; *Cervical Cord/metabolism ; Thoracic Vertebrae ; }, abstract = {Early-onset neurodegeneration leads to cognitive and behavioral symptoms in frontotemporal dementia (FTD) and motor disturbances in amyotrophic lateral sclerosis (ALS). Despite distinct clinical profiles, more than half of FTD patients experience ALS-related symptoms and vice versa. Spinal cord monoamine neurotransmitter alterations were reported in ALS, but not yet in FTD. Therefore, we compared monoaminergic turnover across the FTD-ALS continuum. Reversed-phase, ultra-high-performance liquid chromatography with electrochemical detection was used to measure levels of the monoamines (nor)adrenaline ((N)A), dopamine (DA) and serotonin (5-hydroxytryptamine, 5-HT) and their metabolites 3-methoxy-4-hydroxyphenylglycol (MHPG), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA) in five cervical and thoracic spinal cord regions in 10 FTD, 14 ALS, 6 mixed FTD-ALS, 14 early-onset Alzheimer's disease (EOAD), and 7 control (CONTR) individuals. At the cervical level, NA levels were lower in FTD-ALS versus CONTR, whereas the HVA/5-HIAA ratio was higher in ALS versus EOAD in the lateral funiculus. In the dorsal horn-intermediate gray matter, DA levels were decreased in FTD-ALS compared to FTD. At the thoracic level, DOPAC was lower in ALS than in FTD-ALS patients in the ventral and lateral funiculus, ventral horn, and dorsal horn-intermediate gray matter, as was the DOPAC/DA ratio in the lateral funiculus and dorsal horn-intermediate gray matter. Contrarily, HVA/DA turnover was lower in FTD-ALS than in FTD in the dorsal and ventral funiculus. We observed lower NA levels in FTD-ALS than in FTD in the ventral funiculus, and lower MHPG/NA turnover in the dorsal horn-intermediate gray matter. A levels were lower in ALS versus FTD. This study indicates differences in monoaminergic turnover across the FTD-ALS continuum, at the cervical and thoracic levels, with primarily a decrease in dopaminergic activity in ALS. Characterizing disease-specific neurochemical profiles for FTD, ALS, or FTD-ALS could contribute to the identification of novel interesting pharmacological targets.}, } @article {pmid40143051, year = {2025}, author = {Zou, Y and Zhang, J and Chen, L and Xu, Q and Yao, S and Chen, H}, title = {Targeting Neuroinflammation in Central Nervous System Diseases by Oral Delivery of Lipid Nanoparticles.}, journal = {Pharmaceutics}, volume = {17}, number = {3}, pages = {}, pmid = {40143051}, issn = {1999-4923}, support = {82100892//Hong Chen/ ; 82300929//Jing Zhang/ ; }, abstract = {Neuroinflammation within the central nervous system (CNS) is a primary characteristic of CNS diseases, such as Parkinson's disease, Alzheimer's disease (AD), amyotrophic lateral sclerosis, and mental disorders. The excessive activation of immune cells results in the massive release of pro-inflammatory cytokines, which subsequently induce neuronal death and accelerate the progression of neurodegeneration. Therefore, mitigating excessive neuroinflammation has emerged as a promising strategy for the treatment of CNS diseases. Despite advancements in drug discovery and the development of novel therapeutics, the effective delivery of these agents to the CNS remains a serious challenge due to the restrictive nature of the blood-brain barrier (BBB). This underscores the need to develop a novel drug delivery system. Recent studies have identified oral lipid nanoparticles (LNPs) as a promising approach to efficiently deliver drugs across the BBB and treat neurological diseases. This review aims to comprehensively summarize the recent advancements in the development of LNPs designed for the controlled delivery and therapeutic modulation of CNS diseases through oral administration. Furthermore, this review addresses the mechanisms by which these LNPs overcome biological barriers and evaluate their clinical implications and therapeutic efficacy in the context of oral drug delivery systems. Specifically, it focuses on LNP formulations that facilitate oral administration, exploring their potential to enhance bioavailability, improve targeting precision, and alleviate or manage the symptoms associated with a range of CNS diseases.}, } @article {pmid40141996, year = {2025}, author = {Kodama, TS and Furuita, K and Kojima, C}, title = {Beyond Static Tethering at Membrane Contact Sites: Structural Dynamics and Functional Implications of VAP Proteins.}, journal = {Molecules (Basel, Switzerland)}, volume = {30}, number = {6}, pages = {}, pmid = {40141996}, issn = {1420-3049}, support = {JP22H05536, JP22K19184, JP23H02416, and JP23K18030//Ministry of Education, Culture, Sports, Science and Technology/ ; NMR Platform//Ministry of Education, Culture, Sports, Science and Technology/ ; CR-24-05//Institute for Protein Research, Osaka University/ ; JP24ama121001//Japan Agency for Medical Research and Development/ ; }, mesh = {Humans ; *Vesicular Transport Proteins/metabolism/chemistry/genetics ; Animals ; *Cell Membrane/metabolism ; }, abstract = {The membranes surrounding the eukaryotic cell and its organelles are continuously invaginating, budding, and undergoing membrane fusion-fission events, which enable them to perform functions not found in prokaryotic cells. In addition, organelles come into close contact with each other at membrane contact sites (MCSs), which involve many types of proteins, and which regulate the signaling and transport of various molecules. Vesicle-associated membrane protein (VAMP)-associated protein (VAP) is an important factor involved in the tethering and contact of various organelles at MCSs in almost all eukaryotes and has attracted attention for its association with various diseases, mainly neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS). However, the detailed mechanism of its functional expression remains unclear. In this review, we quantitatively discuss the structural dynamics of the entire molecule, including intrinsically disordered regions and intramolecular and intermolecular interactions, focusing on the vertebrate VAP paralogs VAPA and VAPB. Molecular phylogenetic and biophysical considerations are the basis of the work.}, } @article {pmid40141987, year = {2025}, author = {Russo, A and Putaggio, S and Tellone, E and Calderaro, A and Cirmi, S and Laganà, G and Ficarra, S and Barreca, D and Patanè, GT}, title = {Emerging Ferroptosis Involvement in Amyotrophic Lateral Sclerosis Pathogenesis: Neuroprotective Activity of Polyphenols.}, journal = {Molecules (Basel, Switzerland)}, volume = {30}, number = {6}, pages = {}, pmid = {40141987}, issn = {1420-3049}, mesh = {*Ferroptosis/drug effects ; Humans ; *Amyotrophic Lateral Sclerosis/drug therapy/metabolism/pathology/etiology ; *Neuroprotective Agents/pharmacology/therapeutic use ; *Polyphenols/pharmacology/therapeutic use ; Animals ; Reactive Oxygen Species/metabolism ; Lipid Peroxidation/drug effects ; Mitochondria/metabolism/drug effects ; Oxidative Stress/drug effects ; Iron/metabolism ; }, abstract = {Neurodegenerative diseases are a group of diseases that share common features, such as the generation of misfolded protein deposits and increased oxidative stress. Among them, amyotrophic lateral sclerosis (ALS), whose pathogenesis is still not entirely clear, is a complex neurodegenerative disease linked both to gene mutations affecting different proteins, such as superoxide dismutase 1, Tar DNA binding protein 43, Chromosome 9 open frame 72, and Fused in Sarcoma, and to altered iron homeostasis, mitochondrial dysfunction, oxidative stress, and impaired glutamate metabolism. The purpose of this review is to highlight the molecular targets common to ALS and ferroptosis. Indeed, many pathways implicated in the disease are hallmarks of ferroptosis, a recently discovered type of iron-dependent programmed cell death characterized by increased reactive oxygen species (ROS) and lipid peroxidation. Iron accumulation results in mitochondrial dysfunction and increased levels of ROS, lipid peroxidation, and ferroptosis triggers; in addition, the inhibition of the Xc[-] system results in reduced cystine levels and glutamate accumulation, leading to excitotoxicity and the inhibition of GPx4 synthesis. These results highlight the potential involvement of ferroptosis in ALS, providing new molecular and biochemical targets that could be exploited in the treatment of the disease using polyphenols.}, } @article {pmid40141149, year = {2025}, author = {Zheng, MY and Luo, LZ}, title = {The Role of IL-17A in Mediating Inflammatory Responses and Progression of Neurodegenerative Diseases.}, journal = {International journal of molecular sciences}, volume = {26}, number = {6}, pages = {}, pmid = {40141149}, issn = {1422-0067}, support = {No. 2023D022//the Fujian Provincial Natural Science Foundation/ ; No. 3502Z202473076//the Science and Technology Program of Xiamen City/ ; No. 2019-WJ-30//the Fujian Province Health Education Joint Research Project/ ; }, mesh = {Humans ; *Interleukin-17/metabolism ; *Neurodegenerative Diseases/metabolism/pathology/immunology ; Animals ; *Inflammation/metabolism/pathology ; Signal Transduction ; Disease Progression ; Blood-Brain Barrier/metabolism ; }, abstract = {IL-17A has been implicated as a critical pro-inflammatory cytokine in the pathogenesis of autoimmune and neurodegenerative disorders. Emerging evidence indicates its capacity to activate microglial cells and astrocytes, subsequently inducing the production of inflammatory mediators that exacerbate neuronal injury and functional impairment. Clinical observations have revealed a demonstrated association between IL-17A concentrations and blood-brain barrier (BBB) dysfunction, creating a pathological feedback loop that amplifies neuro-inflammatory responses. Recent advances highlight the cytokine's critical involvement in neurodegenerative disorders through multiple molecular pathways. Therapeutic interventions utilizing monoclonal antibodies (mAbs) against IL-17A or its cognate receptor (IL-17R) have shown promising clinical potential. This review systematically examines the IL-17A-mediated neuro-inflammatory cascades; the mechanistic contributions to neurodegenerative pathology in the established disease models including multiple sclerosis, Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis; and current therapeutic strategies targeting the IL-17A signaling pathways. The analysis provides novel perspectives on optimizing cytokine-directed therapies while identifying the key challenges and research priorities for translational applications in neurodegeneration.}, } @article {pmid40140966, year = {2025}, author = {Balaban, E and Köse, TE and Günaçar, DN and Naralan, ME and Gonca, M}, title = {Comparison of methods for detecting mandibular lingula and can antilingula be used in lingula mandibula detection?.}, journal = {BMC oral health}, volume = {25}, number = {1}, pages = {430}, pmid = {40140966}, issn = {1472-6831}, support = {02025001021255//Recep Tayyip Erdoğan University Development Foundation/ ; }, mesh = {Humans ; Female ; Male ; Retrospective Studies ; Adult ; *Cone-Beam Computed Tomography/methods ; Middle Aged ; *Mandible/diagnostic imaging/anatomy & histology/surgery ; Aged ; Adolescent ; Young Adult ; Aged, 80 and over ; *Orthognathic Surgical Procedures/methods ; Anatomic Landmarks ; Mandibular Nerve ; }, abstract = {OBJECTIVE: The aim of this study is to evaluate the relationship between anatomical reference points used during orthognathic surgery and to minimize the risks of iatrogenic neurovascular damage.

MATERIALS AND METHODS: This retrospective study included cone-beam computed tomography (CBCT) images involving the mandible from patients who visited Recep Tayyip Erdoğan University Faculty of Dentistry between January 2018 and September 2023. The age range of the included individuals was set between 18 and 80 years. Horizontal and vertical distances between mandibular anatomical structures, such as the lingula mandibula (LM), mandibular foramen (MF), antilingula (AL), and surrounding structures were measured using CBCT software. Individuals with intraosseous pathology, insufficient image quality, or a history of surgical/orthodontic treatment were excluded from the study.

RESULTS: A total of 240 hemimandibles from 120 patients were analyzed (55.83% female, 44.17% male; mean age: 46.78 ± 15.30 years). Significant differences were identified in LM positions according to different AL types. The LM was found to be more inferior and posterior relative to hill and ridge type ALs, while it was more anterior relative to plateau type ALs. In 26.25% of mandibular rami, AL was not detected.

CONCLUSION: The position of the AL can serve as a guide in determining the osteotomy line during inferior vertical ramus osteotomy (IVRO). However, relying solely on AL as a reference point may increase the risk of inferior alveolar nerve (IAN) injury. Preoperative tomographic evaluations to determine the relationships among LM, MF, and AL can provide a safer approach in surgical planning, reduce complications, and help protect neurovascular structures.}, } @article {pmid40140908, year = {2025}, author = {Wang, KS and Smeyers, J and Eggan, K and Budnik, B and Mordes, DA}, title = {C9ORF72 poly-PR disrupts expression of ALS/FTD-implicated STMN2 through SRSF7.}, journal = {Acta neuropathologica communications}, volume = {13}, number = {1}, pages = {67}, pmid = {40140908}, issn = {2051-5960}, support = {K08 NS104270/NS/NINDS NIH HHS/United States ; K08NS104270/NS/NINDS NIH HHS/United States ; R01 NS089742/NS/NINDS NIH HHS/United States ; }, mesh = {Humans ; *C9orf72 Protein/genetics/metabolism ; *Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology ; *Frontotemporal Dementia/genetics/metabolism/pathology ; *Serine-Arginine Splicing Factors/metabolism/genetics ; Induced Pluripotent Stem Cells/metabolism ; Axons/metabolism ; Neurons/metabolism ; DNA Repeat Expansion ; }, abstract = {A hexanucleotide repeat expansion in C9ORF72 is the most common genetic cause of amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and combined ALS/FTD. The repeat is transcribed in the sense and the antisense directions to produce several dipeptide repeat proteins (DPRs) that have toxic gain-of-function effects; however, the mechanisms by which DPRs lead to neural dysfunction remain unresolved. Here, we observed that poly-proline-arginine (poly-PR) was sufficient to inhibit axonal regeneration of human induced pluripotent stem cell (iPSC)-derived neurons. Global phospho-proteomics revealed that poly-PR selectively perturbs nuclear RNA binding proteins (RBPs). In neurons, we found that depletion of one of these RBPs, SRSF7 (serine/arginine-rich splicing factor 7), resulted in decreased abundance of STMN2 (stathmin-2), though not TDP-43. STMN2 supports axon maintenance and repair and has been recently implicated in the pathogenesis of ALS/FTD. We observed that depletion of SRSF7 impaired axonal regeneration, a phenotype that could be rescued by exogenous STMN2. We propose that antisense repeat-encoded poly-PR perturbs RBPs, particularly SRSF7, resulting in reduced STMN2 and axonal repair defects in neurons. Hence, we provide a potential link between DPRs gain-of-function effects and STMN2 loss-of-function phenotypes in neurodegeneration.}, } @article {pmid40140666, year = {2025}, author = {de Bernardo, N and de la Rubia Ortí, JE and Villarón-Casales, C and Privado, J and Maset-Roig, R and Cañabate, M and Sancho-Cantus, D and Sanz, IO and Fernández, RF and Proaño, B and Tvarijonaviciute, A and Rubio, CP and Benlloch, M and Menargues-Ramírez, R and Alarcón-Jiménez, J}, title = {Autonomic nervous system and mediating role of respiratory function in patients with ALS.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {10513}, pmid = {40140666}, issn = {2045-2322}, support = {2021-203-003//Universidad Católica de Valencia San Vicente Màrtir/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology ; Male ; Female ; Middle Aged ; *Autonomic Nervous System/physiopathology ; Aged ; Cross-Sectional Studies ; Adult ; Cognition/physiology ; *Respiration ; Oxidative Stress ; Heart Rate/physiology ; Antioxidants/metabolism ; }, abstract = {Patients with Amyotrophic Lateral Sclerosis (ALS) exhibit altered patterns of respiratory rate and heart rhythm that are directly related to autonomic nervous system (ANS) activity. This study aimed to analyze the role of the ANS in respiratory function, cognition, functionality, and antioxidant capacity in patients with ALS through a predictive model that assesses the mediating activity of respiration. This quantitative, observational, analytical, and cross-sectional clinical study was conducted using a sample of 75 patients diagnosed with ALS. ANS activity, respiratory function, cognition, functionality, and antioxidant capacity were also measured. Using these values, a structural equation model was developed using AMOS V.23 software. The mediational predictive model showed that increased sympathetic nervous system (SNS) activity, in turn, increased respiratory function, whereas the role of the parasympathetic nervous system in respiration was very weak and had the opposite effect. Furthermore, SNS activity increased respiratory function values, which, in turn, improved functional capacity, cognition, and antioxidant power in patients with ALS, with respiratory function playing a mediating role. The mediating effect of respiratory function was observed primarily between ANS and functional disability. For oxidative stress, respiratory function showed a high mediating effect, such that greater respiratory function corresponded to greater antioxidant capacity. Additionally, for cognitive activity, a moderate direct effect of the ANS was observed; however, it was greatly enhanced by respiratory disability. Finally, differences were only found based on sex, with respiratory capacity and antioxidant power being higher in men.}, } @article {pmid40140608, year = {2025}, author = {Dubey, SK and Bellen, HJ}, title = {A neuroprotective role of polyunsaturated fatty acids in C9orf72-ALS/FTD.}, journal = {Nature neuroscience}, volume = {28}, number = {4}, pages = {710-712}, pmid = {40140608}, issn = {1546-1726}, } @article {pmid40140376, year = {2025}, author = {Megat, S and Marques, C and Hernán-Godoy, M and Sellier, C and Stuart-Lopez, G and Dirrig-Grosch, S and Gorin, C and Brunet, A and Fischer, M and Keime, C and Kessler, P and Mendoza-Parra, MA and Zwamborn, RAJ and Veldink, JH and Scholz, SW and Ferrucci, L and Ludolph, A and Traynor, B and Chio, A and Dupuis, L and Rouaux, C}, title = {CREB3 gain of function variants protect against ALS.}, journal = {Nature communications}, volume = {16}, number = {1}, pages = {2942}, pmid = {40140376}, issn = {2041-1723}, mesh = {*Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology ; Animals ; *Cyclic AMP Response Element-Binding Protein/genetics/metabolism ; Humans ; Mice ; Male ; Motor Neurons/metabolism/pathology ; *Gain of Function Mutation ; Mice, Transgenic ; Superoxide Dismutase-1/genetics/metabolism ; Motor Cortex/metabolism/pathology ; Disease Models, Animal ; Female ; Disease Progression ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal and rapidly evolving neurodegenerative disease arising from the loss of glutamatergic corticospinal neurons (CSN) and cholinergic motoneurons (MN). Here, we performed comparative cross-species transcriptomics of CSN using published snRNA-seq data from the motor cortex of ALS and control postmortem tissues, and performed longitudinal RNA-seq on CSN purified from male Sod1[G86R] mice. We report that CSN undergo ER stress and altered mRNA translation, and identify the transcription factor CREB3 and its regulatory network as a resilience marker of ALS, not only amongst vulnerable neuronal populations, but across all neuronal populations as well as other cell types. Using genetic and epidemiologic analyses we further identify the rare variant CREB3[R119G] (rs11538707) as a positive disease modifier in ALS. Through gain of function, CREB3[R119G] decreases the risk of developing ALS and the motor progression rate of ALS patients.}, } @article {pmid40139318, year = {2025}, author = {Lai, IC and Wei, JC}, title = {Comment on Vera et al's "Interleukin-23 inhibition associates with lower incidence of cardiovascular risk factor type diseases compared to biologic naïve patients with psoriasis: A retrospective cohort study.".}, journal = {Journal of the American Academy of Dermatology}, volume = {93}, number = {2}, pages = {e51-e52}, doi = {10.1016/j.jaad.2024.12.054}, pmid = {40139318}, issn = {1097-6787}, } @article {pmid40139174, year = {2025}, author = {Toraih, EA and Siddiqui, S and Siddiqui, S and Shirini, K and Elfezzani, N and Abdelmaksoud, A and Elshazli, RM and Hussein, MH and Elmorsy, EM and Fawzy, MS}, title = {Thyroid Disorders as a Risk Factor for Neurodegenerative Proteinopathies: A Large-Scale Propensity Score-Matched Analysis.}, journal = {Neuroepidemiology}, volume = {}, number = {}, pages = {1-13}, doi = {10.1159/000545369}, pmid = {40139174}, issn = {1423-0208}, abstract = {BACKGROUND: The relationship between thyroid disorders and neurodegenerative diseases remains poorly understood. This large-scale retrospective cohort study aimed to investigate the association between thyroid disorders and various neurodegenerative diseases, as well as the potential impact of thyroidectomy.

METHODS: We analyzed data from 3,719,666 patients with thyroid disorders and 2,945,438 controls from 120 healthcare organizations (TriNetX database). After propensity score matching, each group included 2,033,096 patients. We compared the risk of neurodegenerative diseases between these groups and examined the effect of thyroidectomy in a subgroup analysis of 31,753 matched pairs.

RESULTS: Patients with thyroid disorders showed significantly higher risks of Alzheimer's disease (RR = 1.15, 95% CI: 1.110-1.195), Parkinson's disease (RR = 1.25, 95% CI: 1.187-1.318), amyotrophic lateral sclerosis (RR = 1.35, 95% CI: 1.131-1.622), frontotemporal dementia (RR = 1.44, 95% CI: 1.219-1.702), Lewy body dementia (RR = 1.15, 95% CI: 1.107-1.186), progressive supranuclear palsy (RR = 1.41, 95% CI: 1.095-1.819), vascular dementia (RR = 1.32, 95% CI: 1.266-1.369), Niemann-Pick disease type C (RR = 1.34, 95% CI: 1.092-1.638), and Wilson's disease (RR = 1.26, 95% CI: 1.056-1.507). Interestingly, the risk of multiple sclerosis was lower (RR = 0.80, 95% CI: 0.738-0.862). Thyroidectomy was associated with a 44.2% lower risk of Lewy body dementia (RR = 0.558, 95% CI: 0.339-0.919, p = 0.020).

CONCLUSIONS: Thyroid disorders are significantly associated with an increased risk of several neurodegenerative diseases. Thyroidectomy may have a protective effect against Lewy body dementia. These findings suggest a complex relationship between thyroid function and neurodegeneration, emphasizing the need for neurological monitoring in patients with thyroid disorders and further research into thyroid-brain interactions.}, } @article {pmid40138872, year = {2025}, author = {Liang, T and Jiang, T and Liang, Z and Li, L and Chen, Y and Chen, T and Yang, L and Zhang, N and Dong, B and Xie, X and Gu, B and Wu, Q}, title = {Gut microbiota-driven BCAA biosynthesis via Staphylococcus aureus -expressed acetolactate synthase impairs glycemic control in type 2 diabetes in South China.}, journal = {Microbiological research}, volume = {296}, number = {}, pages = {128145}, doi = {10.1016/j.micres.2025.128145}, pmid = {40138872}, issn = {1618-0623}, mesh = {*Diabetes Mellitus, Type 2/microbiology/metabolism ; *Gastrointestinal Microbiome/physiology ; *Staphylococcus aureus/enzymology/genetics/metabolism ; *Amino Acids, Branched-Chain/biosynthesis ; *Acetolactate Synthase/metabolism/genetics ; Humans ; Animals ; Mice ; China ; Male ; Insulin Resistance ; Female ; Middle Aged ; *Glycemic Control ; Blood Glucose ; Feces/microbiology ; Staphylococcal Infections/microbiology ; Metagenomics ; Prediabetic State/microbiology ; Metabolomics ; Insulin ; }, abstract = {An increase in branched-chain amino acid (BCAA) levels can result in insulin resistance at different stages of type 2 diabetes (T2D), however, the causes of this increase are unclear. We performed metagenomics and metabolomics profiling in patients with prediabetes (PDM), newly diagnosed diabetes (NDDM), and post-medication type 2 diabetes (P2DM) to investigate whether altered gut microbes and metabolites could explain the specific clinical characteristics of different disease stages of T2D. Here we identify acetolactate synthase (ALS) a BCAA biosynthesis enzyme in Staphylococcus aureus as a cause of T2D insulin resistance. Compared with healthy peoples, patients with PDM, NDDM, and P2DM groups, especially in P2DM group, have increased faecal numbers of S. aureus. We also demonstrated that insulin administration may be a risk factor for S. aureus infection in T2D. The presence of ALS-positive S. aureus correlated with the levels of BCAAs and was associated with an increased fasting blood glucose (FBG) and insulin resistance. Humanized microbiota transplantation experiment indicated that ALS contributes to disordered insulin resistance mediated by S. aureus. We also found that S. aureus phage can reduced the FBG levels and insulin resistance in db/db mice. The ALS-positive S. aureus are associated with insulin resistance in T2D, opening a new therapeutic avenue for the prevention or treatment of diabetes.}, } @article {pmid40138119, year = {2025}, author = {Ali, N and Sayeed, U and Shahid, SMA and Akhtar, S and Khan, MKA}, title = {Molecular mechanisms and biomarkers in neurodegenerative disorders: a comprehensive review.}, journal = {Molecular biology reports}, volume = {52}, number = {1}, pages = {337}, pmid = {40138119}, issn = {1573-4978}, mesh = {Humans ; *Biomarkers/metabolism/cerebrospinal fluid ; *Neurodegenerative Diseases/metabolism/genetics/diagnosis ; Amyloid beta-Peptides/metabolism/cerebrospinal fluid ; alpha-Synuclein/metabolism/cerebrospinal fluid ; Parkinson Disease/metabolism/genetics ; tau Proteins/metabolism/cerebrospinal fluid ; Alzheimer Disease/metabolism/genetics ; Huntington Disease/genetics/metabolism ; Amyotrophic Lateral Sclerosis/metabolism/genetics ; Dopamine Plasma Membrane Transport Proteins/metabolism ; }, abstract = {Neurodegenerative disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic Lateral Sclerosis (ALS), and Huntington's disease (HD), are significant global health challenges, owing to their profound impact on cognitive, motor, and behavioral functions. The etiology and progression of these disorders are influenced by a complex interplay of environmental factors and genetic predispositions with specific genetic markers, such as mutations in the APOE and HTT genes, which play pivotal roles. Current therapeutic interventions predominantly focus on symptom management; however, emerging strategies, including gene therapies, anti-amyloid agents, and neuroprotective approaches, are designed to directly target the underlying disease mechanisms. Advances in biomarker discovery and imaging methodologies have emerged as essential tools for early diagnosis and monitoring of therapeutic efficacy in these disorders. In the context of AD, cerebrospinal fluid (CSF) amyloid-beta (Aβ) and tau levels, along with positron emission tomography (PET) imaging, are well-established biomarkers. Similarly, CSF alpha-synuclein and dopamine transporter (DAT) imaging have been employed as diagnostic tools for PD. Moreover, emerging biomarkers, such as blood-based tau and the Aβ42/40 ratio for AD, as well as the neurofilament light chain (NfL) for ALS and PD, hold promise for enhancing early diagnostic accuracy and facilitating the longitudinal assessment of disease progression. This study comprehensively examined the molecular mechanisms underlying these neurodegenerative disorders, focusing on amyloid-beta plaque deposition and tau protein aggregation in AD, alpha-synuclein misfolding in PD, and aberrant protein aggregation in ALS and HD, thereby contributing to a deeper understanding of the pathophysiological basis of these disorders.}, } @article {pmid40138021, year = {2025}, author = {Vaughan, DP and Real, R and Jensen, MT and Fumi, RG and Hodgson, M and Jabbari, E and Lux, D and Wu, L and , and , and Warner, TT and Jaunmuktane, Z and Revesz, T and Rowe, JB and Rohrer, J and Morris, HR}, title = {Analysis of C9orf72 repeat length in progressive supranuclear palsy, corticobasal syndrome, corticobasal degeneration, and atypical parkinsonism.}, journal = {Journal of neurology}, volume = {272}, number = {4}, pages = {293}, pmid = {40138021}, issn = {1432-1459}, support = {220258/WT_/Wellcome Trust/United Kingdom ; T033371/1/MRC_/Medical Research Council/United Kingdom ; MC_UU_00030/14//Cambridge Centre for Parkinson-Plus/ ; /WT_/Wellcome Trust/United Kingdom ; NIHR203312//NIHR Cambridge Biomedical Research Centre/ ; PROSPECT2//Progressive Supranuclear Palsy Association/ ; }, mesh = {Humans ; C9orf72 Protein/genetics ; *Supranuclear Palsy, Progressive/genetics ; Male ; Female ; Aged ; *DNA Repeat Expansion/genetics ; *Parkinsonian Disorders/genetics ; Middle Aged ; *Corticobasal Degeneration/genetics ; Aged, 80 and over ; Cohort Studies ; }, abstract = {BACKGROUND: Pathogenic hexanucleotide repeat expansions in C9orf72 are the commonest genetic cause of frontotemporal dementia and/or amyotrophic lateral sclerosis. There is growing interest in intermediate repeat expansions in C9orf72 and their relationship to a wide range of neurological presentations, including Alzheimer's disease, Parkinson's disease, progressive supranuclear palsy, corticobasal degeneration, and corticobasal syndromes.

AIMS: To assess the prevalence of intermediate C9orf72 repeat expansions in a large cohort of prospectively-recruited patients clinically diagnosed with progressive supranuclear palsy (PSP), corticobasal syndrome (CBS), and atypical parkinsonism (APS), compared with healthy controls. We also sought to replicate the association between C9orf72 repeat length and CBD in neuropathologically confirmed cases.

METHODS: 626 cases, including PSP (n = 366), CBS (n = 130), and APS (n = 53) from the PROSPECT study, and 77 cases with pathologically confirmed CBD were screened for intermediate repeat expansions in C9orf72 using repeat-primed PCR. These were compared to controls from the PROSPECT-M-UK study and from the 1958 Birth Cohort.

RESULTS: There was no difference in the mean or largest allele size in any affected patient group compared with controls. A higher proportion of our affected cohort had large C9orf72 repeat expansions compared to controls, but there was no difference when comparing the frequency of intermediate expansions between affected patients and controls. There was no relationship between repeat length and age at onset, level of disability, or survival.

CONCLUSIONS: Intermediate expansions in C9orf72 do not appear to be a genetic risk factor for PSP, CBS, CBD, or atypical parkinsonism. They are not associated with age at onset, disability, or survival in our study.}, } @article {pmid40137226, year = {2025}, author = {Stella, R and Bertoli, A and Lopreiato, R and Peggion, C}, title = {A Twist in Yeast: New Perspectives for Studying TDP-43 Proteinopathies in S. cerevisiae.}, journal = {Journal of fungi (Basel, Switzerland)}, volume = {11}, number = {3}, pages = {}, pmid = {40137226}, issn = {2309-608X}, abstract = {TAR DNA-binding protein 43 kDa (TDP-43) proteinopathies are a group of neurodegenerative diseases (NDs) characterized by the abnormal accumulation of the TDP-43 protein in neurons and glial cells. These proteinopathies are associated with several NDs, including amyotrophic lateral sclerosis, frontotemporal lobar degeneration, and some forms of Alzheimer's disease. Yeast models have proven valuable in ND research due to their simplicity, genetic tractability, and the conservation of many cellular processes shared with higher eukaryotes. For several decades, Saccharomyces cerevisiae has been used as a model organism to study the behavior and toxicity of TDP-43, facilitating the identification of genes and pathways that either exacerbate or mitigate its toxic effects. This review will discuss evidence showing that yeast models of TDP-43 exhibit defects in proteostasis, mitochondrial function, autophagy, and RNA metabolism, which are key features of TDP-43-related NDs. Additionally, we will explore how modulating proteins involved in these processes reduce TDP-43 toxicity, aiding in restoring normal TDP-43 function or preventing its pathological aggregation. These findings highlight potential therapeutic targets for the treatment of TDP-43-related diseases.}, } @article {pmid40136713, year = {2025}, author = {Gao, J and Sikal, A and Hankin, R and Zheng, Y and Sterling, E and Chan, K and Yao, Y}, title = {Extracellular Vesicles from Regenerating Skeletal Muscle Mitigate Muscle Atrophy in an Amyotrophic Lateral Sclerosis Mouse Model.}, journal = {Cells}, volume = {14}, number = {6}, pages = {}, pmid = {40136713}, issn = {2073-4409}, support = {startup//University of Georgia/ ; }, mesh = {Animals ; *Amyotrophic Lateral Sclerosis/pathology/complications/therapy ; *Extracellular Vesicles/metabolism/transplantation ; *Muscular Atrophy/pathology/therapy ; *Muscle, Skeletal/pathology/metabolism ; Disease Models, Animal ; *Regeneration ; Mice ; NF-kappa B/metabolism ; Macrophages/metabolism ; Mice, Inbred C57BL ; Cell Differentiation ; Humans ; Male ; Myoblasts/metabolism ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a devastating neuromuscular disease characterized by progressive motor neuron degeneration and muscle atrophy, with no effective treatments available. Chronic inflammation, which impairs muscle regeneration and promotes proteolysis, is a key contributor to ALS-related muscle atrophy and a promising therapeutic target. Here, we applied extracellular vesicles (EVs) derived from regenerating skeletal muscles 14 days post-acute injury (CTXD14SkM-EVs), which possess a unique anti-inflammatory profile, to target muscle defects in ALS. We found that CTXD14SkM-EVs enhanced myoblast differentiation and fusion in a cellular muscle-wasting model induced by pro-inflammatory cytokine tumor necrosis factor alpha. Intramuscular administration of these EVs into an ALS mouse model mitigated muscle atrophy by promoting muscle regeneration, shifting macrophage polarization from pro-inflammatory M1 to anti-inflammatory M2 state, and suppressing the aberrant Nuclear Factor Kappa B (NF-κB) signaling, a key driver of muscle protein degradation. These results underscore the therapeutic potential of regenerating muscle-derived EVs for combating muscle atrophy in ALS.}, } @article {pmid40136670, year = {2025}, author = {Bond, S and Saxena, S and Sierra-Delgado, JA}, title = {Microglia in ALS: Insights into Mechanisms and Therapeutic Potential.}, journal = {Cells}, volume = {14}, number = {6}, pages = {}, pmid = {40136670}, issn = {2073-4409}, support = {//Rare Village/ ; //Radala Foundation/ ; //University of Missouri- Columbia, School of Medicine/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/therapy/pathology/immunology ; Humans ; *Microglia/pathology/metabolism ; Animals ; Motor Neurons/pathology ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by the loss of motor neurons, leading to escalating muscle weakness, atrophy, and eventually paralysis. While neurons are the most visibly affected, emerging data highlight microglia-the brain's resident immune cells-as key contributors to disease onset and progression. Rather than existing in a simple beneficial or harmful duality, microglia can adopt multiple functional states shaped by internal and external factors, including those in ALS. Collectively, these disease-specific forms are called disease-associated microglia (DAM). Research using rodent models, patient-derived cells, and human postmortem tissue shows that microglia can transition into DAM phenotypes, driving inflammation and neuronal injury. However, these cells can also fulfill protective roles under certain conditions, revealing their adaptable nature. This review explores recent discoveries regarding the multifaceted behavior of microglia in ALS, highlights important findings that link these immune cells to motor neuron deterioration, and discusses emerging therapies-some already used in clinical trials-that aim to recalibrate microglial functions and potentially slow disease progression.}, } @article {pmid40136528, year = {2025}, author = {Chen, X and Wang, Y and Zhang, Y and Li, X and Zhang, L and Gao, S and Zhang, C}, title = {Neural Excitatory/Inhibitory Imbalance in Motor Aging: From Genetic Mechanisms to Therapeutic Challenges.}, journal = {Biology}, volume = {14}, number = {3}, pages = {}, pmid = {40136528}, issn = {2079-7737}, support = {C2406001//the Shenzhen Medical Research Fund/ ; 2024TJCR023//the Tongji Hospital High Quality Clinical Research Fund/ ; 32020103007//the Major International (Regional) Joint Research Project/ ; 2022YFA1206000//the National Key Research and Development Program of China/ ; 32371189, 32300984//the National Natural Science Foundation of China/ ; }, abstract = {Neural excitatory/inhibitory (E/I) imbalance plays a pivotal role in the aging process. However, despite its significant impact, the role of E/I imbalance in motor dysfunction and neurodegenerative diseases has not received sufficient attention. This review explores the mechanisms underlying motor aging through the lens of E/I balance, emphasizing genetic and molecular factors that contribute to this imbalance (such as SCN2A, CACNA1C, GABRB3, GRIN2A, SYT, BDNF…). Key regulatory genes, including REST, vps-34, and STXBP1, are examined for their roles in modulating synaptic activity and neuronal function during aging. With insights drawn from ALS, we discuss how disruptions in E/I balance contribute to the pathophysiology of age-related motor dysfunction. The genes discussed above exhibit a certain association with age-related motor neuron diseases (like ALS), a relationship that had not been previously recognized. Innovative genetic therapies, such as gene editing technology and optogenetic manipulation, are emerging as promising tools for restoring E/I balance, offering hope for ameliorating motor deficits in aging. This review explores the potential of these technologies to intervene in aging-related motor diseases, despite challenges in their direct application to human conditions.}, } @article {pmid40135721, year = {2025}, author = {Fayaz, MU and Wang, Q and Xu, M and Chen, D and Pan, F and Song, C}, title = {Compressive Strain-Induced Uphill Hydrogen Distribution in Strontium Ferrite Films.}, journal = {ACS applied materials & interfaces}, volume = {17}, number = {14}, pages = {21371-21379}, doi = {10.1021/acsami.4c21825}, pmid = {40135721}, issn = {1944-8252}, abstract = {Hydrogen incorporation into metal oxides enhances their electrochemical properties, making them highly suitable for various energy conversion applications. The controlled distribution of hydrogen ions in material systems and their conduction at elevated temperatures have garnered significant attention for various energy storage and environmental monitoring applications, including fuel cells, smart windows, and sensor technologies. In this work, cost-effective, high-concentration hydrogen-doped SrFeO3-δ (HSrFeO3-δ) films were prepared under ambient conditions by treating Al(s)|SrFeO3-δ(s) films with KOH(aq), utilizing electron-proton codoping to investigate hydrogen distribution. The uphill hydrogen distributions in SrFeO3-δ films with compressive strain, in contrast to the density gradient behavior under tensile strain, suggest the fundamental role of the strain states in the hydrogen accommodation. Compressively strained films with a rich Al source follow an anomalous uphill feature of hydrogen distribution, highlighting their potential use as electrolyte for fuel cells. The strain significantly influences the structure, chemical lattice coupling, and consequently the ionic transport in SrFeO3-δ. Ionic conductivity measurements reveal that compressively strained HSrFeO3-δ films with uphill hydrogen distributions exhibit a significant ionic conductivity of 0.189 S/cm at 413 K, with an activation energy of approximately 0.29 eV, making them suitable for low-temperature electrochemical applications. These findings provide a promising approach for tuning material properties and valuable insights for building iontronic devices.}, } @article {pmid40135631, year = {2025}, author = {Novy, C and Tysnes, OB and Busk, ØL and Jaioun, K and Holmøy, T and Holla, ØL and Høyer, H}, title = {Association of UNC13A with increased amyotrophic lateral sclerosis risk, bulbar onset, and lower motor neuron involvement in a Norwegian ALS cohort.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {26}, number = {5-6}, pages = {566-572}, doi = {10.1080/21678421.2024.2447922}, pmid = {40135631}, issn = {2167-9223}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/epidemiology ; Male ; Norway/epidemiology ; Female ; Middle Aged ; Aged ; *Genetic Predisposition to Disease/genetics ; Cohort Studies ; *Motor Neurons/pathology ; *Nerve Tissue Proteins/genetics ; *Polymorphism, Single Nucleotide/genetics ; Genotype ; Gene Frequency ; Adult ; }, abstract = {Objective: Amyotrophic lateral sclerosis (ALS), a progressive neurodegenerative disease characterized by the loss of motor neurons, has limited treatment options available. Treatments targeting specific ALS genes, including UNC13A, have attracted considerable attention. The UNC13A rs12608932 variant has been associated with an increased risk of ALS, shorter survival, and more frequent bulbar onset. Methods: In this study, we investigated the allele frequency of rs12608932 among 500 Norwegian ALS patients, divided into three groups: patients with a genetic cause, patients without a genetic cause, and the entire ALS population. The three groups were compared to two independent control groups. The patients carrying UNC13A genotypes AA, AC, and CC were further clinically characterized and compared using additive, recessive, and dominant models. Results: The frequency of the rs12608932 C allele was higher in the patients with ALS (0.438) than in the controls (0.365; p < 0.001). Among ALS patients without a known genetic cause, individuals with the CC genotype exhibited higher frequencies of bulbar onset (p = 0.015) and prominent lower motor neuron involvement (p = 0.007) than those with the AA and AC genotypes. Conclusions: The CC genotype of rs12608932 is associated with an increased risk of ALS. Additionally, it acts as a modifier of the ALS phenotype, increasing the risk of bulbar onset and dominant lower motor neuron involvement, specifically in patients without a genetic cause in known ALS genes.}, } @article {pmid40135564, year = {2025}, author = {Liang, W and Zhang, C and Wang, D and Su, X and Tan, X and Yang, Y and Cong, C and Wang, Y and Huo, D and Wang, H and Wang, S and Wang, X and Feng, H}, title = {Inhibition of Salt-Inducible Kinase 2 Protects Motor Neurons From Degeneration in ALS by Activating Autophagic Flux and Enhancing mTORC1 Activity.}, journal = {CNS neuroscience & therapeutics}, volume = {31}, number = {3}, pages = {e70341}, pmid = {40135564}, issn = {1755-5949}, support = {2023-KYYWF-0195//Innovative Scientific Research Fund of Harbin Medical University/ ; 82271450//National Natural Science Foundation of China/ ; 82301599//National Natural Science Foundation of China/ ; }, mesh = {Animals ; *Amyotrophic Lateral Sclerosis/pathology/metabolism/genetics ; *Motor Neurons/pathology/metabolism ; *Autophagy/physiology/drug effects ; *Protein Serine-Threonine Kinases/antagonists & inhibitors/metabolism/genetics ; Mice ; *Mechanistic Target of Rapamycin Complex 1/metabolism ; Mice, Transgenic ; Humans ; Male ; Mice, Inbred C57BL ; *Nerve Degeneration/pathology/metabolism ; }, abstract = {OBJECTIVES: Autophagic impairment has been implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS). Salt-inducible kinase 2 (SIK2), a member of the AMP-activated protein kinase (AMPK) family widely expressed in the central nervous system, plays critical roles in neuronal survival, neurogenesis, and the regulation of autophagy. This study aims to investigate the effects and underlying mechanisms of SIK2 in the pathogenesis of ALS.

METHODS: In our work, we used both in vivo and in vitro models of ALS to study the effect of SIK2. Protein and RNA levels were assessed by Western blot, RT-qPCR, immunofluorescence, and immunohistochemistry. Cell viability and apoptosis were evaluated using CCK-8 assay and flow cytometry. Transmission electron microscopy was employed to examine autophagic vacuoles. Additionally, lentivirus particles carrying shRNA targeting SIK2 (sh-SIK2) were injected into the lateral ventricle of ALS mice at 60 days of age. Motor performance was evaluated by the rotarod test.

RESULTS: We observed that increased expression of SIK2 significantly contributed to the degeneration of motor neurons in both the cellular model and the hSOD1[G93A] transgenic mice model of ALS. SIK2 knockdown enhanced neuronal survival and restored mTORC1 activity. Furthermore, SIK2 suppression facilitated the clearance of mutant SOD1 accumulation by activating autophagic flux and enhancing lysosomal acidification. Conversely, SIK2 overexpression impaired mTORC1 activity, exacerbating autophagy dysfunction by inhibiting lysosomal function, and ultimately led to motor neuron degeneration. In vivo, SIK2 deficiency delayed disease onset and extended the lifespan of ALS mice by enhancing autophagy-mediated clearance of mutant SOD1 aggregates.

CONCLUSIONS: Our findings reveal that SIK2 regulates autophagic flux by modulating lysosomal acidification, thereby influencing the degradation of mutant SOD1 aggregates. SIK2 suppression enhances autophagy-mediated clearance of toxic protein aggregates and protects motor neurons, highlighting its potential as a therapeutic target for ALS.}, } @article {pmid40135522, year = {2025}, author = {Bai, D and Fang, Y and Tian, J and Liao, Y and Liu, M and Pan, L}, title = {Tribenuron-methyl resistance in Capsella bursa-pastoris: the co-existence of ALS target enzyme mutation (Pro-197-Ser) and overexpression of GSTF12 and ADP/ATP carrier protein.}, journal = {Pest management science}, volume = {81}, number = {8}, pages = {4365-4372}, doi = {10.1002/ps.8794}, pmid = {40135522}, issn = {1526-4998}, support = {//Scientific Research Fund of Hunan Provincial Education Department/ ; //National Natural Science Foundation of China/ ; //National Key Research and Development Program of China/ ; //China Agriculture Research System/ ; //Modern Agricultural Industrial Technology System of Hunan Province/ ; }, mesh = {*Herbicide Resistance/genetics ; *Herbicides/pharmacology ; *Acetolactate Synthase/genetics/metabolism ; *Arylsulfonates/pharmacology ; Mutation ; *Capsella/genetics/drug effects/enzymology ; *Plant Proteins/genetics/metabolism ; }, abstract = {BACKGROUND: Capsella bursa-pastoris, a prevalent wheat-field weed in China, demonstrates substantial resistance to tribenuron-methyl, a herbicide-targeting acetolactate synthase (ALS). Understanding weed herbicide-resistance mechanisms is crucial for managing resistant weed populations. However, the genes potentially involved in nontarget-site resistance (NTSR) in herbicide-resistant C. bursa-pastoris remain poorly understood and require further investigation. This research aimed to elucidate the resistance level and underlying mechanisms of a field population (R) from Shandong Province, China, to tribenuron-methyl.

RESULTS: Whole-plant bioassays revealed that the relative resistance index (RI) of the R population was 54-fold greater than that of the tribenuron-methyl-sensitive population (S). Additionally, treatment with the cytochrome P450 (CYP450) inhibitor malathion or the glutathione S-transferase (GST) inhibitor 4-Chloro-7-nitro-1,2,3-benzoxadiazole (NBD-Cl) partially mitigated the resistance of the R population to tribenuron-methyl. Sequencing of the ALS target enzyme identified a substitution of proline (CCT) at position 197 with serine (TCT). RNA sequencing combined with quantitative reverse transcription polymerase chain reaction (qRT-PCR) verification identified upregulation of a candidate GST gene (GSTF12) and an ADP/ATP carrier protein in the R population. Heterologous expression of the two candidate genes in yeast cells demonstrated enhanced growth in the presence of tribenuron-methyl.

CONCLUSION: We first identified that, in tribenuron-methyl-resistant C. bursa-pastoris, the Pro-197-Ser mutation in the ALS gene, along with GSTF12 and ADP/ATP carrier protein overexpression, jointly mediate its resistance. This enhances our understanding of herbicide-resistance mechanisms and offers a novel perspective for managing tribenuron-methyl-resistant weeds in agricultural practices. © 2025 Society of Chemical Industry.}, } @article {pmid40134643, year = {2025}, author = {Guo, YX and Yan, X and Liu, XC and Liu, YX and Liu, C}, title = {Artificial intelligence-driven strategies for managing renal and urinary complications in inflammatory bowel disease.}, journal = {World journal of nephrology}, volume = {14}, number = {1}, pages = {100825}, pmid = {40134643}, issn = {2220-6124}, abstract = {In this editorial, we discuss the article by Singh et al published in World Journal of Nephrology, stating the need for timely adjustments in inflammatory bowel disease (IBD) patients' long-term management plans. IBD is chronic and lifelong, with recurrence and remission cycles, including ulcerative colitis and Crohn's disease. It's exact etiology is unknown but likely multifactorial. Related to gut flora and immune issues. Besides intestinal symptoms, IBD can also affect various extraintestinal manifestations such as those involving the skin, joints, eyes and urinary system. The anatomical proximity of urinary system waste disposal to that of the alimentary canal makes early detection and the differentiation of such symptoms very difficult. Various studies show that IBD and it's first-line drugs have nephrotoxicity, impacting the patients' life quality. Existing guidelines give very few references for kidney lesion monitoring. Singh et al's plan aims to improve treatment management for IBD patients with glomerular filtration rate decline, specifically those at risk. Most of IBD patients are young and they need lifelong therapy. So early therapy cessation, taking into account drug side effects, can be helpful. Artificial intelligence-driven diagnosis and treatment has a big potential for management improvements in IBD and other chronic diseases.}, } @article {pmid40133903, year = {2025}, author = {Mitchell, G and Siwela, P and Goldstein, S and Diedericks, AM}, title = {Alcohol industry involvement in the delayed South Africa Draft Liquor Amendment Bill 2016: a case study based on freedom of information requests.}, journal = {Globalization and health}, volume = {21}, number = {1}, pages = {11}, pmid = {40133903}, issn = {1744-8603}, support = {N/A//FORUT/ ; }, mesh = {South Africa ; Humans ; *Alcoholic Beverages/legislation & jurisprudence ; Commerce/legislation & jurisprudence ; *Alcohol Drinking/legislation & jurisprudence ; *Access to Information/legislation & jurisprudence ; }, abstract = {BACKGROUND: South Africa is reported to have one of the highest per capita rates of alcohol consumption among drinkers globally, with alcohol harms exacerbating socio-economic inequalities in the country. The Draft Liquor Amendment Bill 2016 proposed new restrictions on alcohol advertising, availability, and liability of retailers and manufacturers for harm related to any contravention of the regulations. To date, the Bill has not progressed through the legislative process. The alcohol industry is known to use a diverse set of strategies to delay evidence-based policies globally.

METHODS: We aimed to explore Bill-related activity by industry within the National Economic and Development Labour Council, a multi-stakeholder forum that assesses socio-economic policies before they reach parliament. On 06 July 2023 we made a Request for Access to Record, using form two of the Promotion of Access to Information Act (PAIA), no. 2 of 2000 to the National Economic and Development Labour Council for access to minutes of all meetings, reports, and any other publications related to the Bill between January 2016 and December 2022. Informed by Ulucanlar et al's (2023) model and taxonomies of corporate political activity, we extracted data on industry Bill-related activity and thematically analysed key events, presented here as a narrative synthesis.

RESULTS: We identified activity by 14 alcohol industry organisations related to the Bill between 2016 and 2022. Industry representation on five National Economic and Development Labour Council-related committees identified between 2017 and 2021 facilitated their involvement in Bill-related discussions and supported access to other government departments. Community representation was low in all committees compared to industry, labour, and government. Industry funded two socio-economic assessments of the Bill in 2017 and 2022, despite an independent socio-economic impact assessment having already been completed. The 2017 report delayed progress of the Bill, and the 2022 're-evaluation' was more critical of the proposed measures, with the differing conclusions attributed to different methodologies. During the covid-19 pandemic, industry used a 'carrot and stick' approach of legal threats and donations to attempt to move towards self-regulation via a social compact. The National Economic and Development Labour Council confirmed in 2023 that the social compact was unsuccessful.

CONCLUSIONS: Early 'regulatory capture' gave the alcohol industry the opportunity to shape assessment of the Bill within the National Economic and Development Labour Council. Our findings are in line with previous studies on corporate influence on policy globally, and support calls for a reassessment of the role and proportion of industry representation within the National Economic and Development Labour Council locally.}, } @article {pmid40133096, year = {2025}, author = {Shenouda, M and McKeever, PM and Robertson, J}, title = {The long and the short of TDP-43.}, journal = {Trends in neurosciences}, volume = {48}, number = {5}, pages = {313-314}, doi = {10.1016/j.tins.2025.03.003}, pmid = {40133096}, issn = {1878-108X}, mesh = {Humans ; *DNA-Binding Proteins/metabolism/genetics ; Animals ; Protein Isoforms/metabolism/genetics ; }, abstract = {In a recent study, Dykstra and colleagues show that shortened TAR DNA Binding Protein 43 (sTDP-43) isoforms are generated as by-products of TDP-43 autoregulation. sTDP-43 levels are regulated through nonsense-mediated decay and proteasomal and autophagic degradation, and elicit toxicity through dominant negative effects on TDP-43 splicing activity. These results identify mechanisms contributing to sTDP-43 accumulation and toxicity in disease.}, } @article {pmid40132878, year = {2025}, author = {Klickovic, U and Zampedri, L and Zafeiropoulos, N and Ziff, OJ and Sinclair, CD and Wastling, S and Dudziec, M and Allen, J and Trimmel, K and Howard, RS and Malaspina, A and Sharma, N and Sidle, KC and Shah, S and Nasel, C and Yousry, TA and Greensmith, L and Morrow, JM and Thornton, JS and Fratta, P}, title = {Muscle MRI quantifies disease progression in amyotrophic lateral sclerosis.}, journal = {Journal of neurology, neurosurgery, and psychiatry}, volume = {96}, number = {9}, pages = {908-911}, doi = {10.1136/jnnp-2024-335571}, pmid = {40132878}, issn = {1468-330X}, abstract = {BACKGROUND AND OBJECTIVES: Quantitative and operator-independent biomarkers of disease progression are urgently needed in amyotrophic lateral sclerosis (ALS) research. We assess the potential of skeletal muscle MRI as a sensitive and reliable outcome measure for future ALS clinical trials.

METHODS: In this longitudinal cohort study, muscle MRI of head-neck, upper and lower limb regions, alongside clinical and functional assessments, were acquired at three time points over the individual maximum observation period (iMOP) of 1 year in 20 patients with ALS and 16 healthy controls. Quantitative MRI parameters cross-sectional area (CSA), volume (VOL), fat fraction, functional rest muscle area and water T2 (T2m) were correlated with changes in clinical disease severity (functional rating scales and myometry).

RESULTS: Among 20 patients with ALS, 17 completed follow-up. Progressive muscle atrophy (CSA, VOL) was observed at hand (rs=0.66), head-neck (partial η²=0.47) and lower-limb level (thighs: η²=0.56, calves: η²=0.54) over iMOP. MRI changes correlated with leg muscle strength (knee extension: r=0.77; plantar flexion: r=0.78), hand grip strength (r=0.71) and functional rating scales (r=0.68).

INTERPRETATION: Our findings demonstrate the effectiveness of muscle MRI as a sensitive neuroimaging biomarker of disease progression in ALS, highlighting its potential application in clinical trials.}, } @article {pmid40132681, year = {2025}, author = {Wang, Z and Yang, C and Wang, X and Lyu, W and Liao, H and Liu, X and Liu, H and Zhang, J and Shen, H and Zhang, L and Wang, H}, title = {Decoding stress granules dynamics: Implications for neurodegenerative disease.}, journal = {Progress in neurobiology}, volume = {248}, number = {}, pages = {102758}, doi = {10.1016/j.pneurobio.2025.102758}, pmid = {40132681}, issn = {1873-5118}, mesh = {Humans ; *Neurodegenerative Diseases/metabolism ; Animals ; *Stress Granules/metabolism ; }, abstract = {Stress granules (SGs) are membrane-less cytoplasmic structures formed by cells in response to external stress, primarily composed of mRNA and proteins. The dynamic properties of their assembly, maintenance, and disassembly play crucial roles in cellular homeostasis. Recent studies have increasingly revealed that aberrations in SGs dynamics are closely related to the pathogenesis of various neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. This review summarizes the latest research progress on SGs dynamics in neurodegenerative diseases. It begins with an overview of the basic biological characteristics of SGs and their functions in neurons, followed by an in-depth exploration of the mechanisms and regulatory pathways of SGs dynamics. The review then summarizes potential therapeutic strategies targeting SGs dynamics abnormalities, particularly through small molecule drugs to modulate SGs formation and disassembly, aiming to delay or halt the progression of neurodegenerative diseases. The review also highlights the application prospects of these interventions in treating neurodegenerative diseases. Finally, the review introduces current techniques used to study SGs dynamics, discussing their advantages, limitations, and future development possibilities. This review aims to provide researchers with a comprehensive perspective to advance the understanding and clinical application of SGs dynamics in the field of neurodegenerative diseases.}, } @article {pmid40132594, year = {2025}, author = {Zelic, M and Blazier, A and Pontarelli, F and LaMorte, M and Huang, J and Tasdemir-Yilmaz, OE and Ren, Y and Ryan, SK and Shapiro, C and Morel, C and Krishnaswami, P and Levit, M and Sood, D and Chen, Y and Gans, J and Tang, X and Hsiao-Nakamoto, J and Huang, F and Zhang, B and Berry, JD and Bangari, DS and Gaglia, G and Ofengeim, D and Hammond, TR}, title = {Single-cell transcriptomic and functional studies identify glial state changes and a role for inflammatory RIPK1 signaling in ALS pathogenesis.}, journal = {Immunity}, volume = {58}, number = {4}, pages = {961-979.e8}, doi = {10.1016/j.immuni.2025.02.024}, pmid = {40132594}, issn = {1097-4180}, mesh = {*Amyotrophic Lateral Sclerosis/metabolism/pathology/genetics/immunology ; *Receptor-Interacting Protein Serine-Threonine Kinases/metabolism/genetics ; Animals ; Humans ; Mice ; Signal Transduction ; *Neuroglia/metabolism ; Induced Pluripotent Stem Cells/metabolism ; Motor Neurons/metabolism ; *Transcriptome ; Single-Cell Analysis ; Mice, Transgenic ; Superoxide Dismutase-1/genetics ; Inflammation/metabolism ; Microglia/metabolism ; Disease Models, Animal ; Spinal Cord/metabolism/pathology ; Astrocytes/metabolism ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by motor neuron loss. Microglia and astrocyte-driven neuroinflammation is prominent in ALS, but the cell state dynamics and pathways driving disease remain unclear. We performed single-nucleus RNA sequencing of ALS spinal cords and identified altered glial cell states, including increased expression of inflammatory and glial activation markers. Many of these signals converged on the inflammation and cell death regulator receptor-interacting protein kinase 1 (RIPK1) and the necroptotic cell death pathway. In superoxide dismutase 1 (SOD1)[G93A] mice, blocking RIPK1 kinase activity delayed symptom onset and motor impairment and modulated glial responses. We used human induced pluripotent stem cell (iPSC)-derived motor neuron, astrocyte, and microglia tri-cultures to identify potential biomarkers that are secreted upon RIPK1 activation in vitro and modulated by RIPK1 inhibition in the cerebrospinal fluid (CSF) of people with ALS. These data reveal ALS-enriched glial populations associated with inflammation and suggest a deleterious role for neuroinflammatory signaling in ALS pathogenesis.}, } @article {pmid40131525, year = {2025}, author = {Kleinerova, J and Tahedl, M and McKenna, MC and Garcia-Gallardo, A and Hutchinson, S and Hardiman, O and Raoul, C and Ango, F and Schneider, B and Pradat, PF and Tan, EL and Bede, P}, title = {Cerebellar dysfunction in frontotemporal dementia: intra-cerebellar pathology and cerebellar network degeneration.}, journal = {Journal of neurology}, volume = {272}, number = {4}, pages = {289}, pmid = {40131525}, issn = {1432-1459}, support = {JPND-Cofund-2-2019-1/HRBI_/Health Research Board/Ireland ; HRB EIA-2017-019/HRBI_/Health Research Board/Ireland ; ANR France 2022-CEREBRALS//Agence Nationale de la Recherche/ ; }, mesh = {Humans ; *Frontotemporal Dementia/diagnostic imaging/pathology/physiopathology/complications ; Male ; Female ; Middle Aged ; Aged ; *Cerebellum/diagnostic imaging/pathology/physiopathology ; *Amyotrophic Lateral Sclerosis/pathology/diagnostic imaging/physiopathology ; *Cerebellar Diseases/diagnostic imaging/pathology/etiology/physiopathology ; Magnetic Resonance Imaging ; Neural Pathways/diagnostic imaging/pathology/physiopathology ; C9orf72 Protein/genetics ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) share overlapping clinical, genetic, and neuroimaging features; a spectrum of conditions commonly referred to as the ALS-FTD continuum. The majority of imaging studies focus on supratentorial pathology, and phenotype-defining motor, cognitive, and behavioural profiles are often exclusively attributed to supratentorial degeneration overlooking the contribution of cerebellar pathology.

METHODS: A multimodal neuroimaging study was conducted to evaluate phenotype-associated cerebello-cerebral connectivity profiles in ALS-FTD, behavioural variant frontotemporal dementia (bvFTD), non-fluent variant (nfvPPA), and semantic variant primary progressive aphasia (svPPA). Structural connectivity, functional connectivity, and volumetric analyses were conducted.

RESULTS: Radial diffusivity analyses detected impaired bilateral cerebello-frontal, cerebello-parietal, and cerebello-temporal connectivity in all study groups along the ALS-FTD spectrum. Cerebello-occipital disconnection was captured in ALS-FTD and nfvPPA. Spinocerebellar disconnection was detected in C9orf72 negative ALS-FTD and nfvPPA. C9orf72 positive ALS-FTD patients exhibited both anterior and posterior lobe cerebellar volume loss, while bvFTD and nfvPPA patients showed posterior cerebellar atrophy. Flocculonodular degeneration was observed in nfvPPA and cerebellar crura atrophy in bvFTD. Bilateral corticospinal tract and corpus callosum degeneration was detected in ALS-FTD, bvFTD, and nfvPPA. Primary motor cortex volume reductions were captured in both ALS-FTD and nfvPPA.

CONCLUSIONS: Our analyses capture significant cerebro-cerebellar disconnection in frontotemporal dementia. Corticospinal tract and motor cortex degeneration can be readily detected in non-ALS phenotypes. Intra-cerebellar pathology, coupled with the degeneration of cerebellar projections and the ensuing dysfunction of cerebro-cerebellar networks likely contribute to phenotype-defining clinical profiles in frontotemporal dementia. Infratentorial disease burden and cerebellar network dysfunction should, therefore, be carefully considered in FTD, and phenotype-defining neuropsychological profiles should not be solely attributed to supratentorial degeneration.}, } @article {pmid40131291, year = {2025}, author = {Penn, J and McAleer, R and Ziegler, C and Cheskes, S and Nolan, B and von Vopelius-Feldt, J}, title = {Effectiveness of Prehospital Critical Care Scene Response for Major Trauma: A Systematic Review.}, journal = {Prehospital emergency care}, volume = {}, number = {}, pages = {1-14}, doi = {10.1080/10903127.2025.2483978}, pmid = {40131291}, issn = {1545-0066}, abstract = {OBJECTIVES: Major trauma is a leading cause of morbidity and mortality worldwide. It is unclear if the addition of a critical care response unit (CCRU) with capabilities comparable to hospital emergency departments might improve outcomes following major trauma, when added to Basic or Advanced Life Support (BLS/ALS) prehospital care. This systematic review describes the evidence for a CCRU scene response model for major trauma.

METHODS: We searched Medline (Ovid), Embase (Ovid), Cochrane Central Register of Controlled Trials (Ovid), CINAHL (EBSCOhost), Science Citation Index Expanded (Web of Science), Conference Proceedings Citation Index - Science (Web of Science), LILACS (Latin American and Caribbean Health Sciences Literature) for relevant publications from 2003 to 2024. We included any study that compared CCRU and BLS/ALS care at the scene of major trauma, reported patient-focused outcomes, and utilized statistical methods to reduce bias and confounding. The risk of bias was assessed by two independent reviewers, using the ROBINS-I tool. Based on our a priori knowledge of the literature, a narrative analysis was chosen. The review was prospectively registered (PROSPERO ID CRD42023490668).

RESULTS: The search yielded 5243 unique records, of which 26 retrospective cohort studies and one randomized controlled trial met inclusion criteria. Sample sizes ranged from 308 to 153,729 patients. Eighteen of the 27 included studies showed associations between CCRUs and improved survival following trauma, which appear to be more consistently found in more critically injured and adult patients, as well as those suffering traumatic cardiac arrest. The remaining nine studies showed no significant difference in outcomes between CCRU and BLS/ALS care. Most studies demonstrated critical or severe risks of bias.

CONCLUSIONS: Current evidence examining CCRU scene response for major trauma suggests potential benefits in severely injury patients but is limited by overall low quality. Further high-quality research is required to confirm the benefits from CCRU scene response for major trauma.}, } @article {pmid40130694, year = {2025}, author = {Burke, KM and Arulanandam, V and Scirocco, E and Royse, T and Hall, S and Weber, H and Arnold, J and Pathak, P and Walsh, C and Paganoni, S}, title = {Assistive Technology in ALS: A Scoping Review of Devices for Limb, Trunk, and Neck Weakness.}, journal = {American journal of physical medicine & rehabilitation}, volume = {104}, number = {8}, pages = {e115-e124}, pmid = {40130694}, issn = {1537-7385}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/rehabilitation/physiopathology ; *Self-Help Devices ; *Muscle Weakness/rehabilitation/etiology/physiopathology ; Activities of Daily Living ; Torso/physiopathology ; }, abstract = {Amyotrophic lateral sclerosis is a progressive neurodegenerative disease affecting upper and lower motor neurons that control voluntary muscles. With no known cure, clinical care is focused on symptom management to maximize function and quality of life. Assistive technology plays a crucial role and enables some restoration of movement and function despite disease progression. This scoping review assesses the effectiveness of assistive technologies tested in people living with amyotrophic lateral sclerosis, specifically those designed to compensate for upper and lower extremity, trunk, and cervical muscle weakness. A comprehensive search was conducted across PubMed, CINAHL, ERIC, and Google Scholar and through citation chasing. We included 26 articles that tested an assistive device on at least one person living with amyotrophic lateral sclerosis and evaluated the device's effectiveness in restoring movement or providing stabilization to support functional mobility or activities of daily living. Most studies were pilot feasibility or usability trials, with small numbers of amyotrophic lateral sclerosis participants. The devices showed various benefits, including improved range of motion, function, and participation in daily activities. This review highlights the potential for assistive devices to enhance function in people living with amyotrophic lateral sclerosis and underscores the need for comprehensive studies involving larger cohorts of individuals at different stages of amyotrophic lateral sclerosis.}, } @article {pmid40129929, year = {2025}, author = {Liang, F and Sun, Y and Yang, J and Shen, Z and Wang, G and Zhu, J and Zhou, C and Xia, Y}, title = {Gut microbiome is associated with radiotherapy response in lung cancer patients with brain metastases.}, journal = {Frontiers in cellular and infection microbiology}, volume = {15}, number = {}, pages = {1562831}, pmid = {40129929}, issn = {2235-2988}, mesh = {Humans ; *Gastrointestinal Microbiome/radiation effects ; Male ; Female ; *Lung Neoplasms/radiotherapy/pathology ; Middle Aged ; *Brain Neoplasms/radiotherapy/secondary ; Aged ; Feces/microbiology ; RNA, Ribosomal, 16S/genetics ; *Bacteria/classification/genetics/isolation & purification ; Treatment Outcome ; DNA, Bacterial/genetics/chemistry ; }, abstract = {PURPOSE: To investigate the gut microbiome of lung cancer patients with brain metastases undergoing radiotherapy, identify key microorganisms associated with radiotherapy response, and evaluate their potential as biomarkers.

METHODS AND MATERIALS: This study enrolled 55 newly diagnosed lung cancer patients with brain metastases. Fecal samples were collected before radiotherapy and analyzed by 16S rRNA sequencing to assess the gut microbiome's composition and function. Patients were categorized into response (n=28) and non-response (n=27) groups based on treatment efficacy, and α-diversity, β-diversity, and functional pathways were compared between them. Linear Discriminant Analysis Effect Size was used to identify microbial features associated with treatment efficacy. Logistic regression analyses were performed to evaluate the predictive capacity of clinical and microbial factors for treatment outcomes.

RESULTS: No significant difference in α-diversity was observed between the groups (P > 0.05), but β-diversity differed significantly (P = 0.036). Twelve characteristic microorganisms were identified in the response group, including g_ Oscillibacter and g_ Blautia, and nine in the non-response group, such as f_ Desulfovibrionaceae and g_ Megamonas. Metabolic pathways associated with treatment response included ketone body metabolism and pathways related to amyotrophic lateral sclerosis. Multivariate analysis identified g_Flavonifractor (odds ratio [OR] = 6.680, P = 0.004), g_Negativibacillus (OR = 3.862, P = 0.014), C-reactive protein (OR = 1.054, P = 0.017), and systemic inflammation response index (OR = 1.367, P = 0.043) as independent predictors of radiotherapy response. The nomogram and microbiome models achieved area under the curve (AUC) values of 0.935 and 0.866, respectively, demonstrating excellent predictive performance. Decision curve analysis further confirmed these models provided significant net benefits across risk thresholds.

CONCLUSIONS: The composition and functional characteristics of the gut microbiome in lung cancer patients with brain metastases prior to radiotherapy are associated with therapeutic response and possess potential as predictive biomarkers. Further studies are warranted to validate these findings.}, } @article {pmid40129635, year = {2025}, author = {Galaz-Araya, C and Zuñiga-Núñez, D and Salas-Sepúlveda, F and Herrera-Morande, A and Aspée, A and Poblete, H and Zamora, RA}, title = {Theoretical evaluation of a bulky ortho-thioalkyl-azobenzene as an alternative to photocontrol structural cytotoxic effects of metal-free and disulfide oxidized hSOD1 in pathogenesis of ALS.}, journal = {RSC advances}, volume = {15}, number = {12}, pages = {9018-9026}, pmid = {40129635}, issn = {2046-2069}, abstract = {This study presents a novel photopharmacological strategy to mitigate the cytotoxic effects of apo-hSOD1[S-S], a misfolded protein implicated in neurodegenerative diseases. Using quantum chemical calculations and molecular dynamics simulations, we demonstrate that ortho-thio-substituted azobenzene photoswitches (ortho-TABPs) can be employed to precisely modulate the dynamics of the crucial electrostatic loop (EL) in apo-hSOD1[S-S]. We establish that larger ortho-S-alkyl substituents on the ortho-TABP enhance its redox stability, favouring the cis conformation through the modulation of the position of the n → π* transition. This stability is crucial for operation within the reducing cellular environment. Furthermore, we demonstrate the successful and consistent photomodulation of EL conformational dynamics in apo-hSOD1[S-S] through covalent tethering of an ortho-TABP. This control is achieved by leveraging the thermodynamically stable trans conformation of the photoswitch, which allosterically influences the EL and consequently, the geometry of the Zn-binding site, a critical determinant of apo-hSOD1[S-S] cytotoxicity. This work paves the way for developing targeted therapies for neurodegenerative diseases by demonstrating the precise and effective photomodulation of apo-hSOD1[S-S] via rationally designed ortho-TABPs.}, } @article {pmid40128927, year = {2025}, author = {Aikawa, M and Ando, T and Shibayama, H and Kubota, M and Sonoo, M and Fukutake, T}, title = {[A case of amyotrophic lateral sclerosis complicated by syringomyelia associated with Chiari type I malformation].}, journal = {Rinsho shinkeigaku = Clinical neurology}, volume = {65}, number = {4}, pages = {273-277}, doi = {10.5692/clinicalneurol.cn-002045}, pmid = {40128927}, issn = {1882-0654}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/etiology/diagnosis/complications ; *Syringomyelia/surgery/complications/etiology ; Female ; Aged ; *Arnold-Chiari Malformation/complications/surgery ; Decompression, Surgical/adverse effects ; Disease Progression ; Postoperative Complications/etiology ; Foramen Magnum/surgery ; }, abstract = {The patient was a 78-year-old woman. She underwent foramen magnum decompression for syringomyelia associated with Chiari type I malformation, which had developed with difficulty in raising the left upper limb and muscle weakness in both upper limbs. One year after surgery, weight loss of 20 ‍kg, progressive muscle atrophy and weakness in the extremities, paralytic dysarthria, and fasciculation in the bilateral anterior thighs were observed, and needle electromyography showed acute denervation and chronic denervation in the medial vastus muscle. The rapid postoperative progression of symptoms and lower motor neuron symptoms in the lower extremities could not be explained by syringomyelia associated with Chiari type I malformation and were considered a possible complication of amyotrophic lateral sclerosis (ALS). It is possible that the surgery may have caused ALS progression, and attention to the rate of progression of neurologic symptoms may be important in the diagnosis of ALS complications.}, } @article {pmid40128823, year = {2025}, author = {Zhang, W and Huang, C and Yao, H and Yang, S and Jiapaer, Z and Song, J and Wang, X}, title = {Retrotransposon: an insight into neurological disorders from perspectives of neurodevelopment and aging.}, journal = {Translational neurodegeneration}, volume = {14}, number = {1}, pages = {14}, pmid = {40128823}, issn = {2047-9158}, support = {2023TSYCCX0051//Tianshan Talent Training Program/ ; }, mesh = {Humans ; *Retroelements/genetics ; *Aging/genetics ; *Nervous System Diseases/genetics ; Animals ; }, abstract = {Neurological disorders present considerable challenges in diagnosis and treatment due to their complex and diverse etiology. Retrotransposons are a type of mobile genetic element that are increasingly revealed to play a role in these diseases. This review provides a detailed overview of recent developments in the study of retrotransposons in neurodevelopment, neuroaging, and neurological diseases. Retrotransposons, including long interspersed nuclear elements-1, Alu, SINE-VNTR-Alu, and endogenous retrovirus, play important regulatory roles in the development and aging of the nervous system. They have also been implicated in the pathological processes of several neurological diseases, including Alzheimer's disease, X-linked dystonia-parkinsonism, amyotrophic lateral sclerosis, autism spectrum disorder, and schizophrenia. Retrotransposons provide a new perspective for understanding the molecular mechanisms underlying neurological diseases and provide insights into diagnostic and therapeutic strategies of these diseases.}, } @article {pmid40128246, year = {2025}, author = {Hu, X and Wei, M and Zhang, H and Yu, M and Wang, M and Zhou, B and Luo, Y and Li, B}, title = {The experience of pain symptoms in patients with amyotrophic lateral sclerosis: a qualitative study.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {10183}, pmid = {40128246}, issn = {2045-2322}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/complications/psychology/physiopathology ; Male ; Female ; Middle Aged ; Aged ; *Pain/psychology/etiology/physiopathology ; Qualitative Research ; Pain Management ; Adaptation, Psychological ; Adult ; Pain Measurement ; }, abstract = {ALS is a progressive neurodegenerative disease that has a serious impact on patients and their caregivers. For a long time in the past, ALS was considered a painless disease that was largely ignored by clinicians. Describing the complexity and needs of pain symptoms from the perspective of patients can provide the most intuitive direction for future research. The purpose of our research is to explore the experience of pain symptoms in patients with amyotrophic lateral sclerosis (ALS), provide reference for better understanding of pain symptoms in ALS patients. From April 2023 to May 2023, 27 patients experiencing pain symptoms in Peking University Third Hospital who met the diagnostic criteria of "Chinese Guidelines for the Diagnosis and Treatment of amyotrophic lateral sclerosis" were interviewed by means of objective sampling. The content analysis method was used to describe the pain changes since the disease (amyotrophic lateral sclerosis), the factors that aggravate the pain, the measures to cope with the pain and the needs. The interview results included 3 themes and 11 subthemes. (1) Pain is diverse: the type of pain, the time when pain occurs, the change in pain intensity, and the factors that aggravate pain; (2) Individualized pain coping measures: posture adjustment, medication, physical therapy, warmth, emotional regulation; (3) Patients lack of understanding of pain: insufficient source of knowledge, the single orientation of the solution. The nature, location and aggravating factors of pain in amyotrophic lateral sclerosis patients in China are complicated, which should be paid attention to by clinical staff and scientific researchers. The situation of pain management is not optimistic, and the pain of the vast majority of patients has not been effectively alleviated. It is necessary to realize the importance of self-management and care of others in coping with pain, and conduct further research in the future to find a breakthrough in pain relief, so as to strengthen pain intervention in clinical practice.}, } @article {pmid40127736, year = {2025}, author = {Maetani, Y and Kurashige, T and Tada, Y and Kume, K and Watanabe, T and Sotomaru, Y and Yamanaka, K and Maruyama, H and Kawakami, H}, title = {Optineurin knock-out forms TDP-43 aggregates to regulate TDP-43 protein levels despite autophagic up-regulation and aberrant TDP-43 expression.}, journal = {Neuroscience research}, volume = {216}, number = {}, pages = {104893}, doi = {10.1016/j.neures.2025.03.005}, pmid = {40127736}, issn = {1872-8111}, mesh = {Animals ; *Autophagy/physiology ; *DNA-Binding Proteins/metabolism/genetics ; Cell Cycle Proteins/genetics ; *Membrane Transport Proteins/genetics ; Mice ; Mice, Knockout ; Mice, Transgenic ; Up-Regulation ; *Amyotrophic Lateral Sclerosis/metabolism/genetics/pathology ; Spinal Cord/metabolism/pathology ; Motor Neurons/metabolism ; Mice, Inbred C57BL ; Protein Serine-Threonine Kinases/metabolism ; *Transcription Factor TFIIIA/genetics/metabolism ; Disease Models, Animal ; }, abstract = {Optineurin is a causative gene of amyotrophic lateral sclerosis (ALS) and has many roles in processes such as autophagy and inflammation. However, it is unclear how optineurin causes ALS. Optineurin knock-out (Optn-KO) mice, which have been generated by several researchers, exhibit motor neuron degeneration and TDP-43 aggregates, but no motor deficits. Motor dysfunction in ALS model mice is associated with TDP-43 in the spinal cord. We bred Optn-KO mice with TDP-43 overexpression transgenic mice and evaluated whether increased TDP-43 protein causes motor deficits and whether Optn-KO affects TDP-43 protein level. Optn-KO mice had spinal TDP-43 protein levels and motor function comparable to wild-type mice, and TDP-43-transgenic (TDP-43-tg) mice resulted in motor dysfunction and early death. However, double-mutant TDP-43-tg / Optn-KO mice had lower TDP-43 protein levels than TDP-43-tg mice at 18 months age, and showed inhibition of the TBK1-optinerurin autophagic pathway with aging. Furthermore, Optn-KO caused TDP-43-positive cytoplasmic aggregates. TDP-43 overexpression by itself induced spinal microgliosis, but Optn-KO suppressed that microgliosis. Finally, we showed that Optn-KO mice could not exhibit behavioral dysfunction because TDP-43 protein levels were not elevated despite autophagy inhibition. Thus, downregulation of Optn may suppress TDP-43 toxicity by regulating its abundance through aggregate formation.}, } @article {pmid40127392, year = {2025}, author = {Vasta, R and De Mattei, F and Tafaro, S and Canosa, A and Manera, U and Grassano, M and Palumbo, F and Cabras, S and Matteoni, E and Di Pede, F and Zocco, G and Pellegrino, G and Minerva, E and Pascariu, D and Iazzolino, B and Callegaro, S and Fuda, G and Salamone, P and De Marchi, F and Mazzini, L and Moglia, C and Calvo, A and Chiò, A}, title = {Changes to Average Survival of Patients With Amyotrophic Lateral Sclerosis (1995-2018): Results From the Piemonte and Valle d'Aosta Registry.}, journal = {Neurology}, volume = {104}, number = {8}, pages = {e213467}, pmid = {40127392}, issn = {1526-632X}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/mortality/therapy/diagnosis ; Male ; Female ; Registries ; Middle Aged ; Aged ; Adult ; Cohort Studies ; Proportional Hazards Models ; }, abstract = {BACKGROUND AND OBJECTIVES: The average survival of patients with amyotrophic lateral sclerosis (ALS) ranges from 2 to 5 years from symptom onset. However, it remains unclear whether this estimate has improved over time. The objective of this study was to analyze the survival trend of a large population-based cohort of patients with ALS over a 24-year period.

METHODS: Patients from the Piemonte and Valle d'Aosta registry for ALS (PARALS) were categorized into the first (1995-2002), second (2003-2010), or third (2011-2018) epoch based on their diagnosis date. Survival was defined as the time from diagnosis to death, tracheostomy, or censoring date. A Cox proportional hazard model was developed with diagnosis epoch as the primary variable of interest, adjusted for sex, site of onset, age at onset, diagnostic delay, forced vital capacity at diagnosis, Δbody mass index from onset to diagnosis, noninvasive mechanical ventilation use, gastrostomy use, and site of follow-up. A subset analysis comparing the 2007-2012 and 2013-2018 cohorts was conducted, incorporating riluzole prescription, genetics, and preslope category as additional covariates.

RESULTS: A total of 3,134 patients were included, evenly distributed across the 3 epochs (990, 1,023, and 1,121, respectively). The median survival remained stable during the first and second epoch (18.6 months vs 18.3 months) but improved during the third epoch (20.1 months; p = 0.0041), with a hazard ratio (HR) of 0.76 (95% CI 0.67-0.87, p = 0.00003). In the subset analysis, the most recent epoch (2013-2018) showed a continued survival advantage (HR 0.77, 95% CI 0.65-0.90). Of interest, the survival benefit was only evident among intermediate progressors (HR 0.60, 95% CI 0.45-0.80).

DISCUSSION: In the PARALS, ALS survival increased over time. In a subset analysis, the beneficial effect of the epoch was only evident among intermediate progressors. The improvement in multidisciplinary care provided by tertiary centers may be one possible explanation for this finding, although further dedicated studies are needed to confirm this hypothesis.}, } @article {pmid40126464, year = {2025}, author = {Shefner, JM and Cudkowicz, ME and Genge, A and Hardiman, O and Al-Chalabi, A and Andrews, JA and Chio, A and Corcia, P and Couratier, P and de Carvalho, M and Heiman-Patterson, T and Henderson, RD and Ingre, C and Johnston, W and Ludolph, A and Maragakis, NJ and Miller, TM and Mora, JS and Petri, S and Simmons, Z and van den Berg, LH and Zinman, L and Kupfer, S and Malik, FI and Meng, L and Simkins, TJ and Wei, J and Wolff, AA and Rudnicki, SA and , }, title = {Reldesemtiv in Amyotrophic Lateral Sclerosis: Results From the COURAGE-ALS Randomized Clinical Trial.}, journal = {JAMA neurology}, volume = {82}, number = {5}, pages = {477-485}, pmid = {40126464}, issn = {2168-6157}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy ; Male ; Female ; Middle Aged ; Double-Blind Method ; Aged ; Treatment Outcome ; *Oxadiazoles/therapeutic use ; Disease Progression ; Pyrazines ; Pyrimidines ; Imidazoles ; Pyrroles ; Pyridines ; }, abstract = {IMPORTANCE: Treatment options for amyotrophic lateral sclerosis (ALS) remain suboptimal. Results from a phase 2 study of reldesemtiv in ALS suggested that it may slow disease progression.

OBJECTIVE: To assess the effect of reldesemtiv vs placebo on functional outcomes in ALS.

A Study to Evaluate the Efficacy and Safety of Reldesemtiv in Patients With Amyotrophic Lateral Sclerosis (COURAGE-ALS) was a double-blind, placebo-controlled phase 3 randomized clinical trial conducted at 83 ALS centers in 16 countries from August 2021 to July 2023. The first 24-week period was placebo controlled vs reldesemtiv. All participants received reldesemtiv during the second 24-week period with a 4-week follow-up. Two interim analyses were planned, the first for futility and the second for futility and possible resizing. This was a hybrid decentralized trial with approximately half the trial visits performed remotely and the remaining visits in the clinic. Eligible participants met criteria for definite, probable, or possible ALS with lower motor neuron signs by modified El Escorial Criteria, ALS symptoms for 24 months or less, ALS Functional Rating Scale-Revised (ALSFRS-R) total score of 44 or less, and forced vital capacity of greater than or equal to 65% of predicted.

INTERVENTIONS: Oral reldesemtiv, 300 mg, or placebo twice daily.

MAIN OUTCOMES AND MEASURES: The primary end point was change in ALSFRS-R total score from baseline to week 24.

RESULTS: Of the 696 participants screened, 207 were screen failures. A total of 486 participants (mean [SD] age, 59.4 [10.9] years; 309 male [63.6%]) were randomized to reldesemtiv (n = 325) or placebo (n = 161); 3 randomized patients were not dosed. The second interim analysis at 24 weeks after randomization included 256 participants. The data monitoring committee recommended that the trial should end due to futility, and the sponsor agreed. The mean (SE) group difference in the ALSFRS-R score from baseline to week 24 was -1.1 (0.53; 95% CI, -2.17 to -0.08; P = .04, favoring placebo). Given excess missing data from early termination, the combined assessment assumed greater importance; it, too, failed to show a benefit from treatment with reldesemtiv (win probability was 0.44 for reldesemtiv and 0.49 for placebo, with a win ratio of 0.91; 95% CI of win ratio, 0.77-1.10; P = .11).

CONCLUSIONS AND RELEVANCE: This randomized clinical trial failed to demonstrate efficacy for reldesemtiv in slowing functional decline in ALS.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04944784.}, } @article {pmid40126385, year = {2025}, author = {Yarlagadda, S and Hazboun, M and Vilke, G and Farah, J and Donofrio-Odmann, JJ}, title = {Epidemiology of Neonatal Prehospital Care at the San Diego (US) - Tijuana (Mexico) International Border.}, journal = {Prehospital emergency care}, volume = {}, number = {}, pages = {1-6}, doi = {10.1080/10903127.2025.2476196}, pmid = {40126385}, issn = {1545-0066}, abstract = {OBJECTIVES: Neonates, infants 30 days of age or younger are understudied in prehospital emergencies. Our objective was to describe prehospital assessment and care for patients <30 days of age at the San Diego-Tijuana Point of Entry (POE). Additional objectives included describing assessments, care, frequency, and level of care for newborns brought to the border by Mexican ambulances.

METHODS: This was a retrospective analysis from January 1, 2014, to January 01, 2020, of all 9-1-1 calls involving patients <30 days of age at the San Diego POEs. The 9-1-1 responses to newly delivered patients were "newborns". Patients who were not immediately post-delivery were "neonates." Patient demographics, response intervals, clinician interventions, and dispositional data were collected from electronic patient records. Descriptive statistics were applied.

RESULTS: A total of 57 patients <30 days of age were included. With 27 newborn patients, 15 were delivered by emergency medical services (EMS) personnel (27, 55.6%). Initial appearance, pulse, grimace, activity, and respiration (APGAR) scores were 8-10 in 44.4% and 5-7 in 29.6%. Procedures included newborn care (88.9%), advanced life support (ALS) assessment (63.0%), and warming (59.3%). There were five patients that had stimulation, 7 received oxygen, and 3 received Bag-Valve-Mask (BVM) ventilation. No serial heart rates were documented. Regarding 30 neonates, the predominant method of transport to the POE was Mexican ambulance (n 16, 53.3%). Medications administered included oxygen (n 16, 53.3%) and albuterol/ipratropium (n 1, 3.3%). Procedures included ALS assessment (n 19, 63.3%), pulse oximetry (n 22, 73.3%), and 3-lead electrocardiogram (n 8, 26.7%). Three patients (10%) received BVM. Mexican Ambulances brought 16 neonates. A physician or nurse was present in 37.5% of transfers, 50% were incubated, 25% intubated, 37.5% on supplemental oxygen, and 71% had preexisting intravenous access. These were not interfacility transfers but were 9-1-1 activations by U.S. border agents; and 14 neonates did not arrive via Mexican ambulance. Their complaints were respiratory distress (n 7, 50%) and Brief Resolved Unexplained Episode (n 4, 28.6%).

CONCLUSIONS: We found that 9-1-1 transports at the San Diego-Tijuana POE for patients <30 days were few and involved resuscitation, neonates in Mexican ambulances with specialized equipment, physicians, and unfamiliar medications. Neonates arriving via private transport had respiratory distress and BRUE.}, } @article {pmid40125959, year = {2025}, author = {Gupta, U and Kumar, A and Alam, MI and Balaji, PG and Sharma, A and Yadav, AK}, title = {Synthesis and characterization of protein nanohybrid systems for the brain delivery of Riluzole.}, journal = {Therapeutic delivery}, volume = {16}, number = {6}, pages = {569-579}, pmid = {40125959}, issn = {2041-6008}, mesh = {Humans ; *Riluzole/administration & dosage/chemistry ; Cell Survival/drug effects ; Particle Size ; *Brain/metabolism/drug effects ; Animals ; *Serum Albumin, Bovine/chemistry ; *Fullerenes/chemistry ; *Nanoparticles/chemistry ; Cell Line, Tumor ; *Neuroprotective Agents/administration & dosage/chemistry ; Drug Delivery Systems ; Drug Carriers/chemistry ; }, abstract = {AIMS: Synthesis and Characterization of Protein NanoHybrid Systems for the Brain Delivery of Riluzole.

METHODS/MATERIALS: Fullerene is converted into carboxylated fullerene (CF) and then, prepared RZU-loaded BSA nanoparticles conjugated with CF.

RESULTS: The particle size and zeta potential of RZU-PNH were found to be 210 ± 1.15 nm and -18.5 ± 0.615 mV respectively, and entrapment efficiency and loading efficiency of RZU-PNH were found to be 98.8 ± 0.53% and 11.6 ± 0.43%, respectively. The XRD of the RZU-PNH shows the amorphism behavior and CD revealed that secondary structure of the protein mainly consists of α-helix andβ-sheet. The MTT assay showed 88.60% and 90.84% cell viability in both SH-SY5Yand N2a cell lines at a concentration of 20 μg/ml and also, no significant nasal ciliotoxicity was observed after incubation with RZU-PNH.

CONCLUSIONS: Obtained results indicated RZU-PNH formulation to treat amyotrophic lateral sclerosis.}, } @article {pmid40125702, year = {2025}, author = {Madhavan, S and Deshmukh, S and Cummings, M and Doshi, A and Rezania, K and Freels, S and Sawa, G}, title = {Home-Based Tele-tDCS in Amyotrophic Lateral Sclerosis: Feasibility, Safety, and Preliminary Efficacy.}, journal = {Annals of clinical and translational neurology}, volume = {12}, number = {5}, pages = {1022-1033}, pmid = {40125702}, issn = {2328-9503}, support = {R21 HD102722/HD/NICHD NIH HHS/United States ; R21HD102722//Eunice Kennedy Shriver National Institute of Child Health and Human Development/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy ; Female ; Male ; Middle Aged ; Pilot Projects ; Double-Blind Method ; Feasibility Studies ; Aged ; *Transcranial Direct Current Stimulation/methods/adverse effects ; Telemedicine ; Adult ; Disease Progression ; Treatment Outcome ; }, abstract = {OBJECTIVE: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease with limited treatment options. Transcranial direct current stimulation (tDCS) shows promise as a neuromodulatory intervention in various neurological disorders, but its application in ALS, particularly in a remote, home-based format, remains underexplored. This study investigates the feasibility, safety, and preliminary efficacy of remotely supervised tele-tDCS in ALS patients.

METHODS: This double-blinded pilot study included 14 spinal-onset ALS participants randomized into two groups: the intervention group received 72 tele-tDCS sessions over 24 weeks, and the delayed-start group received 36 sham sessions followed by 36 tele-tDCS sessions. Stimulation was delivered at 2 mA for 20 min 3 times a week. Primary outcomes included feasibility, safety, and disease progression measured by the ALS Functional Rating Scale-Revised (ALSFRS-R). Adherence and adverse effects were monitored throughout.

RESULTS: Ten participants completed the study, with an overall compliance rate of 98.3%. No serious adverse events were reported, and mild side effects, like itching and tingling, were consistent with tDCS literature. The intervention group demonstrated a significantly slower decline in ALSFRS-R scores than the delayed-start group. At 24 weeks, the intervention group had a mean ALSFRS-R change of -1.7, compared to -13.6 in the delayed-start group (p = 0.0018). Additionally, the change in ALSFRS-R between pre- and mid-intervention significantly differed between groups (p = 0.0071).

INTERPRETATION: Tele-tDCS was feasible, safe, and well-tolerated in individuals with ALS. Preliminary efficacy results suggest that tele-tDCS may slow disease progression, underscoring the potential of tele-tDCS as a promising home-based neuromodulatory intervention in ALS management.

TRIAL REGISTRATION: Clinical trial registration: NCT04866771.}, } @article {pmid40125691, year = {2025}, author = {Ono, D and Kawai, H and Kuwahara, H and Yokota, T}, title = {Refining Muscle Morphometry Through Machine Learning and Spatial Analysis.}, journal = {Neuropathology and applied neurobiology}, volume = {51}, number = {2}, pages = {e70012}, doi = {10.1111/nan.70012}, pmid = {40125691}, issn = {1365-2990}, mesh = {Humans ; *Machine Learning ; Retrospective Studies ; Male ; *Muscle, Skeletal/pathology ; Female ; Middle Aged ; *Neuromuscular Diseases/pathology ; Spatial Analysis ; Aged ; Adult ; Muscle Fibers, Skeletal/pathology ; *Muscular Diseases/pathology ; }, abstract = {AIMS: Muscle morphology provides important information in differentiating disease aetiology, but its measurement remains challenging because of the lack of an efficient and objective method. This study aimed to quantitatively refine the morphological features of muscle fibres in neuromuscular diseases using machine learning.

METHODS: In this retrospective study, we analysed muscle biopsy specimens on haematoxylin and eosin-staining. Machine learning-based software was developed to segment muscle fibre contours and perform automated muscle morphometry and subsequent graph theory-based spatial analysis of atrophied fibre grouping. A decision tree-based framework, LightGBM, was trained to predict underlying aetiologies based on morphometric and spatial variables.

RESULTS: The study included 100 muscle samples, including 20 normal muscles, 49 myopathies and 19 neuropathies. The fine-tuned segmentation model, YOLOv8, achieved a mask average precision of 0.819. The muscle morphometry revealed the significance of fibre circularity. The mean circularity was higher in the myopathy group, and the SD of circularity was elevated in the neuropathy group. Although most cases were consistent with textbook findings, atypical presentations, such as dermatomyositis with angular atrophy and amyotrophic lateral sclerosis with round atrophy, were objectively documented. Spatial analysis quantified grouped atrophy, showing the potential to feature specific atrophy patterns. The LightGBM model successfully predicted the final clinical diagnosis of the myopathies and neuropathies with an accuracy of 0.852, which exceeded that of 0.808 by human annotation.

CONCLUSION: Automated muscle morphometry and spatial analysis provide quantification of muscle morphology and patterns of atrophy, which will facilitate objective and efficient investigation of neuromuscular diseases.}, } @article {pmid40124885, year = {2025}, author = {Dethier, C and Azirar, S and Verluyten, L and Boonen, H and Grosber, M and Gutermuth, J}, title = {Response to Fässler et al's "Successful treatment of refractory folliculitis decalvans with apremilast".}, journal = {JAAD case reports}, volume = {57}, number = {}, pages = {122-123}, pmid = {40124885}, issn = {2352-5126}, } @article {pmid40124731, year = {2025}, author = {Liu, QZ and Sun, NZ}, title = {Investigation on the quality of life after anterior minimally invasive total hip arthroplasty: Commentary on recent findings.}, journal = {World journal of orthopedics}, volume = {16}, number = {3}, pages = {105318}, pmid = {40124731}, issn = {2218-5836}, abstract = {This editorial critically evaluated the recent study by Ishikura et al, which examined the impact of anterior minimally invasive total hip arthroplasty (MIS-THA) on postoperative quality of life, with a specific focus on the timeline and influencing factors for return to work and resumption of driving. Ishikura et al's research demonstrated that anterior MIS-THA could shorten recovery time, reduce postoperative pain, and significantly enhance patients' quality of life and productivity. Their findings identified occupational type and work intensity as key determinants of postoperative recovery. By synthesizing evidence from multiple studies, this analysis systematically evaluated the clinical advantages of anterior MIS-THA-including reduced soft tissue trauma and accelerated functional recovery-while acknowledging its limitations, such as a steep surgical learning curve and early postoperative complication risks. The discussion emphasized the necessity of designing personalized rehabilitation protocols that accounted for patients' occupational demands. Notably, while current findings primarily derived from retrospective analyses, the article highlighted the need for prospective cohort studies to validate these observations. The commentary also addressed ongoing debates in the field, particularly the elevated complication rates associated with the direct anterior approach compared to posterior techniques, thereby underscoring the critical role of surgeon expertise in optimizing procedural safety. Collectively, this evaluation advanced our understanding of postoperative recovery dynamics in anterior MIS-THA and provides evidence-based insights to refine clinical rehabilitation frameworks.}, } @article {pmid40122623, year = {2025}, author = {Ghanizada, H and Nedergaard, M}, title = {The glymphatic system.}, journal = {Handbook of clinical neurology}, volume = {209}, number = {}, pages = {161-170}, doi = {10.1016/B978-0-443-19104-6.00006-1}, pmid = {40122623}, issn = {0072-9752}, mesh = {Humans ; *Glymphatic System/metabolism/physiology ; Animals ; *Neurodegenerative Diseases ; *Brain/metabolism ; }, abstract = {The glymphatic system, a brain-wide network-supporting cerebrospinal fluid (CSF) and interstitial fluid (ISF) exchange, is essential for removing metabolic waste from the brain. This system's proper functioning is crucial for maintaining neural health and preventing the accumulation of harmful substances that can lead to neurodegenerative diseases. This chapter explores the glymphatic system's mechanisms, its dysfunction in various neurologic disorders, and potential therapeutic strategies. Recent discoveries reveal the glymphatic system's involvement in aging, sleep, cerebral edema, and conditions, such as Alzheimer, Parkinson, Huntington diseases, amyotrophic lateral sclerosis, small vessel disease, hydrocephalus, migraine, stroke, traumatic brain injury, and psychiatric disorders, where impaired waste clearance contributes to disease pathogenesis. Moreover, therapeutic interventions targeting glymphatic dysfunction present promising avenues for mitigating the effects of neurodegenerative diseases. The chapter underscores the potential of integrating glymphatic research into broader clinical practices, offering new strategies for disease management and prevention.}, } @article {pmid40122396, year = {2025}, author = {Cao, Y and Xu, Y and Cao, M and Chen, N and Zeng, Q and Lai, MKP and Fan, D and Sethi, G and Cao, Y}, title = {Fluid-based biomarkers for neurodegenerative diseases.}, journal = {Ageing research reviews}, volume = {108}, number = {}, pages = {102739}, doi = {10.1016/j.arr.2025.102739}, pmid = {40122396}, issn = {1872-9649}, mesh = {Humans ; *Biomarkers/cerebrospinal fluid/blood/metabolism ; *Neurodegenerative Diseases/diagnosis/blood/cerebrospinal fluid/metabolism ; Amyloid beta-Peptides/blood ; tau Proteins/blood ; }, abstract = {Neurodegenerative diseases, such as Alzheimer's Disease (AD), Multiple Sclerosis (MS), Parkinson's Disease (PD), and Amyotrophic Lateral Sclerosis (ALS) are increasingly prevalent as global populations age. Fluid biomarkers, derived from cerebrospinal fluid (CSF), blood, saliva, urine, and exosomes, offer a promising solution for early diagnosis, prognosis, and disease monitoring. These biomarkers can reflect critical pathological processes like amyloid-beta (Aβ) deposition, tau protein hyperphosphorylation, α-syn misfolding, TDP-43 mislocalization and aggregation, and neuronal damage, enabling detection long before clinical symptoms emerge. Recent advances in blood-based biomarkers, particularly plasma Aβ, phosphorylated tau, and TDP-43, have shown diagnostic accuracy equivalent to CSF biomarkers, offering more accessible testing options. This review discusses the current challenges in fluid biomarker research, including variability, standardization, and sensitivity issues, and explores how combining multiple biomarkers with clinical symptoms improves diagnostic reliability. Ethical considerations, future directions involving extracellular vehicles (EVs), and the integration of artificial intelligence (AI) are also highlighted. Continued research efforts will be key to overcoming these obstacles, enabling fluid biomarkers to become crucial tools in personalized medicine for neurodegenerative diseases.}, } @article {pmid40120962, year = {2025}, author = {Zhang, X and Wang, J and Zhang, J and Jiang, C and Liu, X and Wang, S and Zhang, Z and Rastegar-Kashkooli, Y and Dialameh, F and Peng, Q and Tao, J and Ding, R and Wang, J and Cheng, N and Wang, M and Wang, F and Li, N and Xing, N and Chen, X and Fan, X and Wang, J and Wang, J}, title = {Humanized rodent models of neurodegenerative diseases and other brain disorders.}, journal = {Neuroscience and biobehavioral reviews}, volume = {172}, number = {}, pages = {106112}, doi = {10.1016/j.neubiorev.2025.106112}, pmid = {40120962}, issn = {1873-7528}, mesh = {Animals ; *Disease Models, Animal ; Humans ; *Neurodegenerative Diseases/genetics/pathology/physiopathology ; *Brain Diseases ; Rodentia ; }, abstract = {Central Nervous System (CNS) diseases significantly affect human health. However, replicating the onset, progression, and pathology of these diseases in rodents is challenging. To address this issue, researchers have developed humanized animal models. These models introduce human genes or cells into rodents. As a result, rodents become more suitable for studying human CNS diseases and their therapies in vivo. This review explores the preparation protocols, pathological and behavioral characteristics, benefits, significance, and limitations of humanized rodent models in researching various CNS diseases, particularly Alzheimer's disease, Parkinson's disease, Huntington's disease, Amyotrophic lateral sclerosis, glial cells-related CNS diseases, N-methyl-D-aspartic acid receptor encephalitis, and others. Humanized rodent models have expanded the opportunities for in vivo exploration of human neurodegenerative diseases, other brain disorders, and their treatments. We can enhance translational research on CNS disorders by developing, investigating, and utilizing these models.}, } @article {pmid40119776, year = {2025}, author = {Pesti, B and Langa, X and Kumpesa, N and Valdeolivas, A and Sultan, M and Rottenberg, S and Hahn, K}, title = {Mini Review: Spatial Transcriptomics to Decode the Central Nervous System.}, journal = {Toxicologic pathology}, volume = {53}, number = {4}, pages = {397-402}, doi = {10.1177/01926233251325204}, pmid = {40119776}, issn = {1533-1601}, mesh = {Humans ; Animals ; *Transcriptome ; *Central Nervous System/metabolism ; *Gene Expression Profiling/methods ; Neurodegenerative Diseases/genetics ; }, abstract = {Spatial transcriptomics (ST) is revolutionizing our understanding of the central nervous system (CNS) by providing spatially resolved gene expression data. This mini review explores the impact of ST on CNS research, particularly in neurodegenerative diseases like Alzheimer's, Parkinson's, multiple sclerosis, and amyotrophic lateral sclerosis. We describe two foundational ST methods: sequencing-based and imaging-based. Key studies are reviewed highlighting the power of ST data sets to map transcriptomes to disease-specific histomorphology, elucidate molecular mechanisms of regional and cellular vulnerability, integrate single-cell data with tissue mapping, and reveal receptor-ligand interactions. Despite current challenges like data interpretation and resolution limits, ST holds promise for identifying novel drug targets, evaluating their therapeutic potential, and bridging gaps between animal models and human studies to advance development of CNS-targeting compounds.}, } @article {pmid40119207, year = {2025}, author = {Cheng, M and Lu, D and Li, K and Wang, Y and Tong, X and Qi, X and Yan, C and Ji, K and Wang, J and Wang, W and Lv, H and Zhang, X and Kong, W and Zhang, J and Ma, J and Li, K and Wang, Y and Feng, J and Wei, P and Li, Q and Shen, C and Fu, XD and Ma, Y and Zhang, X}, title = {Author Correction: Mitochondrial respiratory complex IV deficiency recapitulates amyotrophic lateral sclerosis.}, journal = {Nature neuroscience}, volume = {28}, number = {4}, pages = {913}, doi = {10.1038/s41593-025-01941-2}, pmid = {40119207}, issn = {1546-1726}, } @article {pmid40118328, year = {2025}, author = {Mansour, HM and El-Khatib, AS}, title = {Oligonucleotide-based therapeutics for neurodegenerative disorders: Focus on antisense oligonucleotides.}, journal = {European journal of pharmacology}, volume = {998}, number = {}, pages = {177529}, doi = {10.1016/j.ejphar.2025.177529}, pmid = {40118328}, issn = {1879-0712}, mesh = {Humans ; *Oligonucleotides, Antisense/therapeutic use/chemistry ; *Neurodegenerative Diseases/drug therapy/genetics/therapy ; Animals ; }, abstract = {Antisense oligonucleotides (ASOs) specifically bind to target RNA sequences and regulate protein expression through various mechanisms. ASOs are a promising therapeutic approach for treating neurodegenerative diseases. The ASO field is a growing area of drug development that focuses on targeting the root cause of diseases at the RNA level, providing a promising alternative to therapies that target downstream processes. Addressing challenges related to off-target effects and inadequate biological activity is essential to successfully develop ASO-based therapies. Researchers have investigated various chemical modifications and delivery strategies to overcome these challenges. This review discusses oligonucleotide-based therapies, particularly ASOs. We discuss the chemical modifications and mechanisms of action of ASOs. Additionally, we recap the results of preclinical and clinical studies testing different ASOs in various neurodegenerative disorders, including spinal muscular atrophy, Huntington's disease, amyotrophic lateral sclerosis, Alzheimer's disease, and Parkinson's disease. In conclusion, ASO drugs show promise as a therapeutic option for treating neurodegenerative diseases.}, } @article {pmid40117902, year = {2025}, author = {Wi, JH and Lee, H and Park, JM and Heo, Y and Jo, S and Lee, J and Kim, Y and Jung, C and Kim, NJ and Song, GY and Kim, P and Kim, H and Lee, S}, title = {Development of a TBK1 and ALK dual inhibitor for alleviating depressive behavior via anti-inflammatory effects.}, journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie}, volume = {186}, number = {}, pages = {117991}, doi = {10.1016/j.biopha.2025.117991}, pmid = {40117902}, issn = {1950-6007}, mesh = {Animals ; *Protein Serine-Threonine Kinases/antagonists & inhibitors/metabolism ; *Anaplastic Lymphoma Kinase/antagonists & inhibitors/metabolism ; Mice ; *Anti-Inflammatory Agents/pharmacology/therapeutic use ; *Protein Kinase Inhibitors/pharmacology ; *Depression/drug therapy/enzymology ; Lipopolysaccharides ; Humans ; Male ; Disease Models, Animal ; *Behavior, Animal/drug effects ; Mice, Inbred C57BL ; Signal Transduction/drug effects ; *Antidepressive Agents/pharmacology ; }, abstract = {Polypharmacology offers innovative strategies for treating immune and inflammatory dysregulation in complex diseases. Here, we identified ALS-04, a dual inhibitor of TANK-binding kinase 1 (TBK1) and anaplastic lymphoma kinase (ALK), which are closely linked to stimulator of interferon genes (STING)-mediated immune responses. ALS-04 effectively suppressed 2'3'-cyclic GMP-AMP (cGAMP)- and lipopolysaccharide (LPS)-induced type I interferon and pro-inflammatory responses by targeting the STING-TBK1 and STING-ALK pathways. Furthermore, ALS-04 significantly alleviated depressive symptoms, including anhedonia and behavioral despair, in an LPS-induced mouse model of depression. These findings highlight the therapeutic potential of dual TBK1 and ALK inhibition in depression by modulating immune and inflammatory pathways.}, } @article {pmid40117341, year = {2025}, author = {Koehn, LM and Steele, JR and Schittenhelm, RB and Nicolazzo, JA}, title = {Sex-Specific Markers of Neuroinflammation and Neurodegeneration in the Spinal Cord Proteome of the SOD1[G93A] Mouse Model of Amyotrophic Lateral Sclerosis.}, journal = {Journal of proteome research}, volume = {24}, number = {4}, pages = {1956-1970}, doi = {10.1021/acs.jproteome.4c00990}, pmid = {40117341}, issn = {1535-3907}, mesh = {Animals ; *Amyotrophic Lateral Sclerosis/metabolism/genetics/pathology ; Female ; *Spinal Cord/metabolism/pathology ; Mice ; Male ; Disease Models, Animal ; *Proteome/genetics/metabolism ; *Superoxide Dismutase-1/genetics ; Proteomics/methods ; Biomarkers/metabolism ; Mice, Transgenic ; *Neuroinflammatory Diseases/metabolism/pathology/genetics ; Sex Factors ; Sex Characteristics ; Superoxide Dismutase/genetics ; Humans ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder that has no cure. The underlying mechanistic details of sex differences in the ALS spinal cord, the site of disease onset, are not understood to an extent that could guide novel drug development. To address this, the spinal cords of 120-day-old wild-type (WT) and SOD1[G93A] (familial mouse model of ALS with mutant superoxide dismutase 1) mice were subjected to untargeted, quantitative proteomics using tandem mass tag acquisition on high-resolution mass spectrometric instrumentation. Compared to WT, both male and female SOD1[G93A] spinal cords exhibited an upregulation of neuroinflammatory cascades of both peripheral and central origins, as well as a downregulation of proteins reflective of death and dysfunction of cells within the spinal cord. However, female and male SOD1[G93A] mouse spinal cords exhibited sex-specific differences in proteins compared to respective WT that related to immune response, as well as cellular structure, function, and homeostasis. The proteomic datasets presented provide entire cohort and sex-specific spinal cord drug targets and disease biomarkers in the SOD1[G93A] mouse model of ALS that may guide future drug development and sex selection in preclinical study designs utilizing the SOD1[G93A] model.}, } @article {pmid40116411, year = {2025}, author = {Albrethsen, J and Drici, L and Slot Vilmann, LM and Holmboe, SA and Thomsen, CE and Rogaczewska Groendahl, VL and Ottenheijm, ME and Nielsen, AB and Christoffersen, C and Aksglaede, L and Hagen, CP and Wewer Albrechtsen, NJ and Juul, A}, title = {Targeted proteomics of serum IGF-I, -II, IGFBP-2, -3, -4, -5, -6 and ALS.}, journal = {Clinical chemistry and laboratory medicine}, volume = {63}, number = {8}, pages = {1528-1537}, pmid = {40116411}, issn = {1437-4331}, mesh = {Humans ; *Proteomics/methods ; Insulin-Like Growth Factor Binding Protein 2/blood ; *Insulin-Like Growth Factor I/analysis ; Insulin-Like Growth Factor Binding Protein 3/blood ; Child ; *Insulin-Like Growth Factor II/analysis ; Adolescent ; Tandem Mass Spectrometry ; Insulin-Like Growth Factor Binding Protein 5/blood ; *Insulin-Like Growth Factor Binding Proteins/blood ; *Glycoproteins/blood ; Insulin-Like Growth Factor Binding Protein 4/blood ; Male ; Female ; *Carrier Proteins/blood ; Insulin-Like Growth Factor Binding Protein 6/blood ; Chromatography, High Pressure Liquid ; }, abstract = {OBJECTIVES: The insulin-like growth factors (IGFs) regulate growth in humans. IGF-I and IGF binding protein (IGFBP)-3 are biomarkers in children with growth disorders. We investigate a targeted proteomics method for absolute quantitation of eight IGF protein family members in human serum, including the peptide hormones IGF-I and -II, and the six binding proteins IGFBP-2, -3, -4, -5, -6 and acid labile subunit (ALS).

METHODS: Serum preparation was optimized for targeted proteomics of IGF related proteins on a clinical LC-MS/MS platform (UHPLC coupled with Triple-Q MS). We created quality controls, standards and internal standards and 289 serum samples from healthy children and adolescents were measured in ten batches over two months. The method was compared to WHO reference standards, clinical and research immunoassays, and relative proteomics profiling.

RESULTS: The sensitivity and reproducibility were sufficient for most but not all IGF protein family members. Targeted proteomics correlated well with clinical immunoassays for IGF-I (R[2]=0.88) and for IGFBP-3 (R[2]=0.46), (p<0.001). The correlation between targeted proteomics and non-clinical immunoassays for IGF-II, IGFBP-2, -4, -5, -6 and ALS varied between proteins.

CONCLUSIONS: We present a method for parallel quantification of IGF-I, IGFBP-3, 5 and ALS for clinical verification studies, whereas targeted proteomics of the five remaining IGF related proteins (IGF-II, IGFBP-2, -4, and -6) require further examination. The sensitivity of our new IGF-I method suggests a possible diagnostic role for targeted proteomics of IGF-I in the management of children with extremely low levels of circulating IGF-I.}, } @article {pmid40116377, year = {2025}, author = {Zhu, Y and Li, M and Zhou, M and Hong, D}, title = {Letter on Wine Glass Sign in Bulbar-Onset Amyotrophic Lateral Sclerosis.}, journal = {Annals of neurology}, volume = {97}, number = {6}, pages = {1222}, doi = {10.1002/ana.27239}, pmid = {40116377}, issn = {1531-8249}, } @article {pmid40116361, year = {2025}, author = {Li, C and Noonan, AM and Hays, J and Roychowdhury, S and Malalur, P and Elkhatib, R and Manne, A and Mittra, A and Rahman, S and Yan, L and Hill, K and Abbott, N and Phelps, M and Na, JY and Liang, B and Storts, H and Khan, M and Zhang, EH and Miles, W and Yildiz, V and Wei, L and Wang, JJ and Jin, N}, title = {Riluzole in Combination with mFOLFOX6 and Bevacizumab in Treating Patients with Metastatic Colorectal Cancer: A Phase I Clinical Trial.}, journal = {Clinical cancer research : an official journal of the American Association for Cancer Research}, volume = {31}, number = {11}, pages = {2115-2123}, pmid = {40116361}, issn = {1557-3265}, support = {K12 CA133250/CA/NCI NIH HHS/United States ; P30 CA016058/CA/NCI NIH HHS/United States ; R01 CA273924/CA/NCI NIH HHS/United States ; K12CA133250//Paul Calabresi Career Development Award for Clinical Oncology/ ; }, mesh = {Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; *Antineoplastic Combined Chemotherapy Protocols/administration & dosage ; Bevacizumab/administration & dosage ; *Colorectal Neoplasms/drug therapy/pathology/mortality ; Fluorouracil/administration & dosage ; Leucovorin/administration & dosage ; Neoplasm Metastasis ; Organoplatinum Compounds/administration & dosage ; Riluzole/administration & dosage ; Treatment Outcome ; }, abstract = {PURPOSE: Colorectal cancer is the second leading cause of cancer-related mortality in the United States. Chemotherapies based on 5-fluorouracil (5-FU), when combined with targeted agents, remain the standard of care for patients with metastatic or locally advanced disease. New treatment strategies are needed for patients with metastatic colorectal cancer with microsatellite stable disease. Preclinical studies have shown that riluzole, an oral medicine for amyotrophic lateral sclerosis, inhibits glutamate release and synergizes with 5-fluorouracil to reduce cell viability in colorectal cancer cell lines.

PATIENTS AND METHODS: In this single-arm, phase I trial of riluzole in combination with mFOLFOX6/bevacizumab for patients with metastatic colorectal cancer, the riluzole dose started at 50 mg twice daily, escalating to 100 mg twice daily or de-escalating to 50 mg once daily. Patients received riluzole for 16 weeks in combination with mFOLFOX6/bevacizumab for eight cycles. Patients then either continued mFOLFOX6/bevacizumab or switched therapies.

RESULTS: Twelve of the 14 patients enrolled were evaluable. All patients had previously received FOLFOX, and five patients (41.7%) showed disease resistance to it. Two patients obtained partial responses, nine had stable disease, and one had progressive disease. The objective response rate was 16.7%, and the disease control rate was 91.7%. The median duration of response was 4.9 months (95% confidence interval, 1.6-9.8). Median progression-free survival and overall survival were 4.89 and 12.98 months, respectively.

CONCLUSIONS: Our study showed that riluzole plus mFOLFOX6/bevacizumab is well tolerated in patients with metastatic colorectal cancer and may have clinical activity in patients whose disease is resistant to FOLFOX.}, } @article {pmid40116017, year = {2025}, author = {Addy, G and Scirocco, E and Gelevski, D and Rohrer, M and Roderick, A and McCormack, M and Weiss Sadan, A and Scalia, J and Parikh, N and Giacomelli, E and Locatelli, M and Neel, DV and D'Agostino, D and Leite, A and Yu, H and Sherman, AV and Mock, J and Kalmes, A and Luppino, S and Babu, S and Berry, J and Cudkowicz, M and Paganoni, S}, title = {An Expanded Access Protocol of RNS60 in Amyotrophic Lateral Sclerosis.}, journal = {Muscle & nerve}, volume = {72}, number = {1}, pages = {124-129}, pmid = {40116017}, issn = {1097-4598}, support = {T32 GM144273/GM/NIGMS NIH HHS/United States ; //The study drug was provided at no cost by Revalesio, and program costs were covered by philanthropic donations to the Sean M. Healey & AMG Center for ALS/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/drug therapy ; Humans ; Middle Aged ; Male ; Female ; Aged ; Adult ; Pilot Projects ; Nebulizers and Vaporizers ; Treatment Outcome ; }, abstract = {AIMS: RNS60 is an investigational product in clinical development for amyotrophic lateral sclerosis (ALS). RNS60 slowed disease progression in the ALS SOD1[G93A] mouse model and was safe and well tolerated both in an open-label pilot study and a randomized, placebo-controlled, multicenter phase 2 trial in people living with ALS. The objective of this ongoing expanded access protocol (EAP) was to provide RNS60 to people living with ALS who are ineligible for controlled clinical trials and to collect data on the safety and tolerability of dosing RNS60 via twice-daily nebulization rather than the previously studied daily nebulization with weekly intravenous administration.

METHODS: Eligible participants (≥ 18 years old, diagnosed with ALS per investigator assessment, and ineligible for an ALS clinical trial testing RNS60) were treated with twice-daily nebulization of RNS60 at home. Safety was evaluated by the assessment of adverse events and routine safety labs.

RESULTS: A total of 84 participants have been treated with RNS60 via nebulization twice daily for up to 48 months so far. The most common treatment-related adverse event was increased secretions [N = 27 (32%)]. Serious adverse events (SAEs) [69 occurrences; N = 38 (45%) with at least one SAE] and deaths [N = 24 (28%)] were deemed not related to RNS60.

DISCUSSION: This EAP supports the benign side effect profile of RNS60 when administered via twice-daily nebulization and demonstrates the feasibility of long-term EAPs as a complementary approach to controlled trials in people with advanced ALS.}, } @article {pmid40113485, year = {2025}, author = {Anzilotti, S and Franco, C and Valsecchi, V and Cuomo, O and Lombardi, G and Di Muraglia, N and De Iesu, N and Laudati, G and Annunziato, L and Canzoniero, LMT and Pignataro, G}, title = {Modulation of ZnT-1 by Let7a unveils a therapeutic potential in amyotrophic lateral sclerosis.}, journal = {Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics}, volume = {22}, number = {3}, pages = {e00571}, pmid = {40113485}, issn = {1878-7479}, mesh = {*Amyotrophic Lateral Sclerosis/metabolism/pathology/genetics/drug therapy ; Animals ; *Cation Transport Proteins/metabolism/genetics ; Mice ; *MicroRNAs/metabolism/genetics ; Mice, Transgenic ; Spinal Cord/metabolism/pathology ; Humans ; Motor Neurons/metabolism/pathology ; Disease Models, Animal ; Microglia/metabolism ; Superoxide Dismutase/genetics ; }, abstract = {The imbalance in cellular ionic homeostasis represents a hallmark of several neurodegenerative diseases, including Amyotrophic Lateral Sclerosis (ALS). Zinc Transporter 1 (ZnT1), the first described member of the ZnT family, stands out as the sole member of the SLC30 family responsible for exporting cytosolic zinc to the extracellular space. While ZnT1 is expressed across all tissues and cell types studied, it exhibits the highest prominence within the central nervous system. In ALS SOD1[G93A] mice, a reduction in ZnT1 expression consistent with disease progression has been observed, prompting our investigation into its role in ALS pathophysiology. Remarkably, through the use of a sequence complementary to the microRNA let-7a (anti-Let-7a) able to modulate ZnT1 expression, we demonstrated in ALS mice its capability to: (1) prevent the reduction in ZnT1 levels in the spinal cord; (2) preserve motor neuron survival in the ventral spinal horn; (3) decrease astroglial and microglial activation while sparing resident microglial cells in the spinal cord; and (4) improve the lifespan and alleviate motor symptoms.}, } @article {pmid40109661, year = {2025}, author = {Hong, Y and Shi, JQ and Feng, S and Huang, SQ and Yuan, ZH and Liu, S and Zhang, XH and Zhou, JS and Jiang, T and Zhao, HD and Zhang, YD}, title = {The systemic inflammation markers as potential predictors of disease progression and survival time in amyotrophic lateral sclerosis.}, journal = {Frontiers in neuroscience}, volume = {19}, number = {}, pages = {1552949}, pmid = {40109661}, issn = {1662-4548}, abstract = {INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a fatal and untreatable neurodegenerative disease with only 3-5 years' survival time after diagnosis. Inflammation has been proven to play important roles in ALS progression. However, the relationship between systemic inflammation markers and ALS has not been well established, especially in Chinese ALS patients. The present study aimed to assess the predictive value of systemic inflammation markers including neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), lymphocyte to monocyte ratio (LMR), and systemic immune-inflammation index (SII) for Chinese amyotrophic lateral sclerosis (ALS).

METHODS: Seventy-two Chinese ALS patients and 73 controls were included in this study. The rate of disease progression was calculated as the change of Revised ALS Functional Rating Scale (ALSFRS-R) score per month. Patients were classified into fast progressors if the progression rate > 1.0 point/month and slow progressors if progression rate ≤ 1.0 point/month. The value of NLR, PLR, LMR, and SII were measured based on blood cell counts. The association between systemic inflammation markers and disease progression rate was confirmed by logistic regression analysis. Kaplan-Meier curve and Cox regression models were used to evaluate factors affecting the survival outcome of ALS patients.

RESULTS: For Chinese ALS patients, NLR, PLR and SII were higher, LMR was lower when compared with controls. All these four markers were proved to be independent correlated with fast progression of ALS. Both Kaplan-Meier curve and Cox regression analysis indicated that higher NLR and lower LMR were associated with shorter survival time in the ALS patients.

DISCUSSION: In conclusion, the systemic inflammation markers, especially NLR and LMR might be independent markers for rapid progression and shorter survival time in Chinese ALS patients.}, } @article {pmid40109277, year = {2025}, author = {Ding, XY and Habimana, JD and Li, ZY}, title = {The role of DPP6 dysregulation in neuropathology: from synaptic regulation to disease mechanisms.}, journal = {Frontiers in cellular neuroscience}, volume = {19}, number = {}, pages = {1547495}, pmid = {40109277}, issn = {1662-5102}, abstract = {As a transmembrane protein, DPP6 modulates the function and properties of ion channels, playing a crucial role in various tissues, particularly in the brain. DPP6 interacts with potassium channel Kv4.2 (KCND2), enhancing its membrane expression and channel kinetics. Potassium ion channels are critical in progressing action potential formation and synaptic plasticity. Therefore, dysfunction of DPP6 can lead to significant health consequences. Abnormal DPP6 expression has been identified in several diseases, such as amyotrophic lateral sclerosis (ALS), autism spectrum disorder (ASD), spinal bulbar muscular atrophy (SBMA), and idiopathic ventricular fibrillation. Recent research has indicated a connection between DPP6 and Alzheimer's disease as well. The most common symptoms resulting from DPP6 dysregulation are mental deficiency and muscle wastage. Notably, these symptoms do not always occur at the same time. Besides genetic factors, environmental factors also undoubtedly play a role in diseases related to DPP6 dysregulation. However, it remains unclear how the expression of DPP6 gets regulated. This review aims to summarize the associations between DPP6 and neurological diseases, offering insights as well as proposing hypotheses to elucidate the underlying mechanisms of DPP6 dysregulation.}, } @article {pmid40108302, year = {2025}, author = {Ma, W and Polgár, E and Dickie, AC and Hajer, MA and Quillet, R and Gutierrez-Mecinas, M and Yadav, M and Hachisuka, J and Todd, AJ and Bell, AM}, title = {Anatomical characterisation of somatostatin-expressing neurons belonging to the anterolateral system.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {9549}, pmid = {40108302}, issn = {2045-2322}, support = {MR/S002987/1/MRC_/Medical Research Council/United Kingdom ; 219433/Z/19/Z/WT_/Wellcome Trust/United Kingdom ; 304005/Z/23/Z/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Animals ; *Somatostatin/metabolism/genetics ; Mice ; *Neurons/metabolism/cytology ; *Spinal Cord/metabolism/cytology ; Axons/metabolism ; Mice, Transgenic ; }, abstract = {Anterolateral system (ALS) spinal projection neurons are essential for pain perception. However, these cells are heterogeneous, and there has been extensive debate about the roles of ALS populations in the different pain dimensions. We recently performed single-nucleus RNA sequencing on a developmentally-defined subset of ALS neurons, and identified 5 transcriptomic populations. One of these, ALS4, consists of cells that express Sst, the gene coding for somatostatin, and we reported that these were located in the lateral part of lamina V. Here we use a Sst[Cre] mouse line to characterise these cells and define their axonal projections. We find that their axons ascend mainly on the ipsilateral side, giving off collaterals throughout their course in the spinal cord. They target various brainstem nuclei, including the parabrachial internal lateral nucleus, and the posterior triangular and medial dorsal thalamic nuclei. We also show that in the L4 segment Sst is expressed by ~ 75% of ALS neurons in lateral lamina V and that there are around 120 Sst-positive lateral lamina V cells on each side. Our findings indicate that this is a relatively large population, and based on projection targets we conclude that they are likely to contribute to the affective-motivational dimension of pain.}, } @article {pmid40106466, year = {2025}, author = {Lemmers, SAM and Le Luyer, M and Stoll, SJ and Hoffnagle, AG and Ferrell, RJ and Gamble, JA and Guatelli-Steinberg, D and Gurian, KN and McGrath, K and O'Hara, MC and Smith, ADAC and Dunn, EC}, title = {Inter-rater reliability of stress signatures in exfoliated primary dentition - Improving scientific rigor and reproducibility in histological data collection.}, journal = {PloS one}, volume = {20}, number = {3}, pages = {e0318700}, pmid = {40106466}, issn = {1932-6203}, mesh = {Humans ; Reproducibility of Results ; *Tooth, Deciduous/pathology ; Observer Variation ; *Dental Enamel/pathology ; *Stress, Physiological ; Male ; Female ; }, abstract = {Accentuated Lines (ALs) in tooth enamel can reflect metabolic disruptions from physiological or psychological stresses during development. They can therefore serve as a retrospective biomarker of generalized stress exposure in archaeological and clinical research. However, little consensus exists on when ALs are identified and inter-rater reliability is poorly quantified across studies. Here, we sought to address this gap by examining the reliability of accentuated (AL) markings across raters, in terms of both the presence versus absence of ALs and their intensity (HAL= Highly Accentuated, MAL= Mildly Accentuated, RL= Retzius Line). Ratings were made and compared across observers (with different levels of experience) and pairs of raters (who agreed on AL coding through consensus meetings) (N = 15 teeth, eight observers). Results indicated that more experience in AL assessment does not necessarily produce higher reliability between raters. Most disagreements in intensity ratings occurred in categories other than HAL. Furthermore, when AL assessment was performed by pairs of raters, reliability was significantly higher than individual assessments (Gwet's AC1 = 0.28 to 0.56 for line presence assessment; Gwet's AC1 = 0.48 to 0.64 for line intensity assessment). Based on these results, we recommend a workflow called IRRISS (Improving Reliability and Reporting In Scoring of Stress-markers) to increase rigor and reproducibility in histological analysis of dental collections. The introduction of IRRISS is well-timed, given the surge in studies of teeth occurring across anthropological, epidemiological, medical, forensic, and climate research fields.}, } @article {pmid40105438, year = {2025}, author = {Ueha, R and Dealino, MA and Koyama, M and Yamakawa, K and Matsumoto, N and Sato, T and Goto, T and Mizukami, A and Kondo, K}, title = {Improved Pharyngeal Contraction and Oral Intake Status After Modified Central-Part Laryngectomy for Late-Stage ALS.}, journal = {Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery}, volume = {173}, number = {1}, pages = {154-161}, pmid = {40105438}, issn = {1097-6817}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/surgery/physiopathology/complications ; Male ; Retrospective Studies ; *Laryngectomy/methods ; Aged ; Middle Aged ; Female ; *Deglutition Disorders/etiology/surgery/physiopathology ; *Pharynx/physiopathology/surgery ; *Deglutition/physiology ; }, abstract = {OBJECTIVE: To investigate the effects of modified central-part laryngectomy with pharyngeal space reduction (CPL-PR) on patients with weak deglutitive pharyngeal contraction, as seen in late-stage amyotrophic lateral sclerosis (ALS).

STUDY DESIGN: Retrospective case series.

SETTING: Single-institution academic center.

METHODS: Patients with late-stage ALS confined at The University of Tokyo Hospital between 2019 and March 2024 in whom CPL-PR had been performed were identified. Patients who had undergone simultaneous pharyngeal flap surgery or had no preoperative high-resolution manofluorography done were excluded. Preoperatively, penetration-aspiration scale (PAS) scores were determined via videofluoroscopic swallowing study. Functional oral intake scale (FOIS) scores and high-resolution manometric parameters were measured and compared preoperatively and postoperatively.

RESULTS: Eighteen patients were identified with a median age of 66.5 (interquartile range [IQR]: 58.0-74.8). The median preoperative PAS score was 7.5 (IQR: 5.5-8.0), indicating severe dysphagia. There was significant improvement in oral intake status with FOIS scores increasing from 1 (IQR: 1-1) to 3 (IQR: 2-3) at 3 months postoperatively (P = .0002). Significant increases in velopharyngeal closure integral (P = .024) and mesohypopharyngeal contractile integral (P = .0001) were observed. Upper esophageal sphincter (UES) resting pressure was reduced (P = .0002), and UES relaxation time was prolonged during swallowing (P < .0001).

CONCLUSION: There were tangible improvements in pharyngeal contraction, UES bolus passage, and oral intake status following CPL-PR, which contribute to regaining oral intake in late-stage ALS. CPL-PR is an option for patients requiring tracheostomy who wish to prevent aspiration and regain their ability to take food orally.}, } @article {pmid40105291, year = {2025}, author = {Ozeki-Hayashi, R and Wilkinson, DJC}, title = {'An Unimaginable Challenge': A Cross-Cultural Qualitative Study of Ethics and Decision-Making Around Tracheostomy Ventilation in Patients with Amyotrophic Lateral Sclerosis.}, journal = {AJOB empirical bioethics}, volume = {}, number = {}, pages = {1-13}, doi = {10.1080/23294515.2025.2474928}, pmid = {40105291}, issn = {2329-4523}, abstract = {BACKGROUND: The rate of tracheostomy with invasive ventilation (TIV) for patients with Amyotrophic Lateral Sclerosis (ALS) varies widely. Previous studies have shown that doctors' values may affect decision-making. There have been no previous international qualitative comparisons of medical decision-making process for TIV or why practice varies.

METHODS: We conducted semi-structured in-depth interviews with 16 doctors actively involved in the management of ALS patients from Japan (n = 7), the UK (n = 5), and the US (n = 4). We used three hypothetical cases to explore decision-making. Conversations were transcribed and thematically analyzed.

RESULTS: Our data reveals similarities but also marked differences in views between the US, the UK and Japan. Almost all participants stated that they ought to respect patient autonomy. However, their approaches varied. British participants wanted to (and felt that they should) respect patient autonomy, but they also believed that TIV was not a realistic option. US participants were likely to prioritize patient autonomy over other ethical principles, and Japanese participants were likely to limit patient autonomy indirectly. The option of TIV appeared to be heavily influenced by the availability of healthcare resources in all three countries. The high cost, limited availability and difficulty of treatment meant that particularly in the UK and the US, it is challenging to receive TIV even if patients wanted this.

CONCLUSIONS: Our study illustrates how the emphasis on autonomy varies along with variations in the way care is organized in the setting of highly resource intensive treatment and progressive severe disabling illness. There is a need to review elements of the decision-making process in all three countries. This includes the need for transparent, ideally centralized, decision-making guidelines about the provision of TIV. Although we investigated a rare neuromuscular disease, our results will be relevant to other diseases requiring highly resource-intensive treatment toward the end of life.}, } @article {pmid40105198, year = {2025}, author = {Gotkine, M and Schoenfeld, DA and Cohen, I and Shefner, JM and Lerner, Y and Cohen, IR and Klein, C and Ovadia, E and Cudkowicz, ME and , }, title = {Akt Activation With IPL344 Treatment for Amyotrophic Lateral Sclerosis: First in Human, Open-Label Study.}, journal = {Muscle & nerve}, volume = {71}, number = {6}, pages = {1032-1042}, pmid = {40105198}, issn = {1097-4598}, support = {//Immunity Pharma/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy/blood ; Male ; Female ; Middle Aged ; Aged ; Neurofilament Proteins/blood ; *Proto-Oncogene Proteins c-akt/metabolism ; Treatment Outcome ; Disease Progression ; Adult ; }, abstract = {INTRODUCTION/AIMS: Akt intracellular signal transduction pathway dysfunction has been reported in people with amyotrophic lateral sclerosis (ALS) providing a novel target for intervention in this devastating progressive disease. This first-in-human study evaluated the safety, tolerability, and preliminary efficacy of the Akt pathway activator, IPL344, in people with ALS.

METHODS: Nine participants with ALS and a progression rate > 0.55 points/month on the Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) received open-label IPL344 treatment (once-daily) for up to 36 months. Safety was assessed through adverse event (AE) reporting. Plasma neurofilament light chain (NfL) concentrations were measured before and after treatment. Clinical outcomes were compared to historical data.

RESULTS: The mean ± SD duration of IPL344 follow-up was 14.0 ± 12.5 months. One participant developed drug hypersensitivity, two had central venous catheter-related AEs, and two had serious pneumonia AEs. The unadjusted mean ± SE slope of decline in ALSFRS-R was -0.53 ± 0.15 (48% slower progression vs. historical controls, p = 0.028). Adjustment for disease stage and rate-indicating covariates indicated a 64% slower ALSFRS-R progression (p = 0.034), with increased rather than reduced body weight (p = 0.02). Eight of nine IPL344-treated participants had a significantly improved slope compared to the median slope of a matched control group (p = 0.04). Plasma NfL concentrations were lowered by 27% (n = 6). Unadjusted median survival for participants in the IPL344 group was 43.4 months [95% CI: 20.5, NA] compared with 19.1 months [17.4, 23.0] in the historical control group.

DISCUSSION: These preliminary data indicate that IPL344 was safe and well-tolerated, and possibly effective. Our findings may merit further investigation in a larger placebo-controlled clinical trial.}, } @article {pmid40103545, year = {2025}, author = {Sonaglioni, A and Torretta, P and Nicolosi, GL and Lombardo, M}, title = {Left ventricular mechanics assessment in amyloidosis patients: a systematic review and meta-analysis.}, journal = {Minerva cardiology and angiology}, volume = {}, number = {}, pages = {}, doi = {10.23736/S2724-5683.24.06683-3}, pmid = {40103545}, issn = {2724-5772}, abstract = {BACKGROUND: Over the last decade, a small number of studies have used speckle tracking echocardiography (STE) or cardiac magnetic resonance (CMR) for measuring left ventricular (LV) mechanics in patients with amyloidosis. This systematic review and meta-analysis aimed at assessing the overall influence of amyloidosis on LV global longitudinal strain (GLS) and regional longitudinal strain at basal (BLS), mid (MLS) and apical (ALS) level, respectively.

METHODS: All imaging studies assessing LV-GLS, LV-BLS, LV-MLS and LV-ALS in amyloidosis patients versus healthy controls, selected from PubMed and EMBASE databases, were included. The risk of bias was assessed by using the National Institutes of Health (NIH) Quality Assessment of Case-Control Studies. Continuous data (LV-GLS, LV-BLS, LV-MLS and LV-ALS) were pooled as a standardized mean differences (SMDs) comparing amyloidosis group with healthy controls. The overall SMDs of LV-GLS, LV-BLS, LV-MLS and LV-ALS were calculated using the random-effect model.

RESULTS: The full-texts of 13 studies with 553 amyloidosis patients and 575 healthy controls were analyzed. STE (53.8%) and CMR (46.2%) studies were separately analyzed. Average LV-GLS magnitude was significantly impaired in amyloidosis patients vs. controls in both STE (13.8±3.9 vs. 19.8±2.7%) and CMR (12.3±4 vs. 17.9±3.5%) studies. The impairment of segmental strain detected in amyloidosis patients was prevalent at basal and mid level, with relative "apical sparing." SMDs obtained for LV-GLS (SMD -1.80, 95% CI: -2.35, -1.24, P <0.001), LV-BLS (-1.98; 95% CI: -2.51, -1.45, P <0.001) and LV-MLS (-1.84; 95% CI: -2.46, -1.23, P <0.001) assessment were significantly larger than that obtained for LV-ALS (-0.72; 95% CI: -1.31, -0.13, P=0.02) measurement. Substantial heterogeneity was found among the studies assessing LV-GLS (I[2]=92.5%), LV-BLS (I[2]=91.4%), LV-MLS (I[2]=94.3%) and LV-ALS (I[2]=94.6%). Egger's test yielded a P value of 0.10, 0.20, 0.09 and 0.55 for LV-GLS, LV-BLS, LV-MLS and LV-ALS assessment respectively, indicating no publication bias. On meta-regression analysis, none of the moderators was significantly associated with effect modification for LV-GLS, LV-BLS, LV-MLS and LV-ALS (all P<0.05).

CONCLUSIONS: Amyloidosis has a large negative effect on LV-GLS, primarily related to the deterioration of segmental longitudinal strain at the basal and mid level, with relative apical sparing.}, } @article {pmid40102416, year = {2025}, author = {Rivas-Fernández, JP and Vuillemin, M and Pilgaard, B and Klau, LJ and Fredslund, F and Lund-Hanssen, C and Welner, DH and Meyer, AS and Morth, JP and Meilleur, F and Aachmann, FL and Rovira, C and Wilkens, C}, title = {Unraveling the molecular mechanism of polysaccharide lyases for efficient alginate degradation.}, journal = {Nature communications}, volume = {16}, number = {1}, pages = {2670}, pmid = {40102416}, issn = {2041-1723}, support = {315385//Norges Forskningsråd (Research Council of Norway)/ ; 226244//Norges Forskningsråd (Research Council of Norway)/ ; 294946//Norges Forskningsråd (Research Council of Norway)/ ; DFF170746//Det Frie Forskningsråd (Danish Council for Independent Research)/ ; 2021-SGR-00680//Government of Catalonia | Agència de Gestió d'Ajuts Universitaris i de Recerca (Agency for Management of University and Research Grants)/ ; NNF10CC1016517//Novo Nordisk Fonden (Novo Nordisk Foundation)/ ; }, mesh = {*Alginates/metabolism/chemistry ; *Polysaccharide-Lyases/metabolism/chemistry/genetics ; Catalytic Domain ; Kinetics ; Crystallography, X-Ray ; Molecular Dynamics Simulation ; Substrate Specificity ; }, abstract = {Alginate lyases (ALs) catalyze the depolymerization of brown macroalgae alginates, widely used naturally occurring polysaccharides. Their molecular reaction mechanism remains elusive due to the lack of catalytically competent Michaelis-Menten-like complex structures. Here, we provide structural snapshots and dissect the mechanism of mannuronan-specific ALs from family 7 polysaccharide lyases (PL7), employing time-resolved NMR, X-ray, neutron crystallography, and QM/MM simulations. We reveal the protonation state of critical active site residues, enabling atomic-level analysis of the reaction coordinate. Our approach reveals an endolytic and asynchronous syn β-elimination reaction, with Tyr serving as both Brønsted base and acid, involving a carbanion-type transition state. This study not only reconciles previous structural and kinetic discrepancies, but also establishes a comprehensive PL reaction mechanism which is most likely applicable across all enzymes of the PL7 family as well as other PL families.}, } @article {pmid40102061, year = {2025}, author = {Tran, K and Hayes, HA and Bromberg, M}, title = {A prospective observational study of decision-making by patients with amyotrophic lateral sclerosis upon recommendation for PEG enteral feeding tubes.}, journal = {Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition}, volume = {40}, number = {3}, pages = {623-629}, pmid = {40102061}, issn = {1941-2452}, mesh = {Humans ; *Enteral Nutrition/psychology/methods/instrumentation ; *Amyotrophic Lateral Sclerosis/therapy/psychology ; Prospective Studies ; *Gastrostomy/psychology/methods ; Female ; Male ; Middle Aged ; Aged ; *Decision Making ; Patient Satisfaction ; Adult ; Surveys and Questionnaires ; Intubation, Gastrointestinal ; }, abstract = {OBJECTIVE: To understand challenges surrounding acceptance of a percutaneous endoscopic gastroscopic enteral feeding tube by patients with amyotrophic lateral sclerosis: a prospective observational study.

METHODS: This was a prospective observational study of 41 patients and care partners attending a multidisciplinary Motor Neuron Disease clinic. Surveys were administered pregastrostomy tube placement (N = 23) and postplacement (N = 41). Some were not available both pre- and postplacement). For preplacement, we queried barriers affecting their decision for receiving a gastrostomy tube at the time of recommendation. For postplacement, we queried factors that influenced their decision as well as perceived benefit and satisfaction with use.

RESULTS: Patient concerns about receiving a gastrostomy tube centered on the procedure, possible pain/infection (48%), limitations on activities (44%), impact on body image, and possible extension of life. For patients who received a gastrostomy tube, satisfaction was very high (93%), and there was reduced patient (59%) and care partners (54%) stress. The average BMI was 28.6 kg/m[2] at diagnosis, and there was no net gain in weight. The average time until placement of a gastrostomy tube following recommendation was 145 days (range 13-824 days).

CONCLUSIONS: Despite counseling at multiple time points, the decision to obtain a feeding tube is often challenging for patients and care partners. Gastrostomy tube placement was perceived as a substantial benefit. Addressing these barriers may reduce concerns and promote earlier decision-making to maximize the benefits of placing a gastrostomy tube sooner.}, } @article {pmid40100917, year = {2025}, author = {Thau-Habermann, N and Gschwendtberger, T and Bodemer, C and Petri, S}, title = {Parthenolide regulates microglial and astrocyte function in primary cultures from ALS mice and has neuroprotective effects on primary motor neurons.}, journal = {PloS one}, volume = {20}, number = {3}, pages = {e0319866}, pmid = {40100917}, issn = {1932-6203}, mesh = {Animals ; *Microglia/drug effects/metabolism/pathology ; *Amyotrophic Lateral Sclerosis/pathology/metabolism/drug therapy ; *Motor Neurons/drug effects/metabolism/pathology ; *Neuroprotective Agents/pharmacology ; *Sesquiterpenes/pharmacology ; Mice ; *Astrocytes/drug effects/metabolism ; Superoxide Dismutase-1 ; Superoxide Dismutase/genetics/metabolism ; Cells, Cultured ; }, abstract = {Over the last twenty years, the role of microgliosis and astrocytosis in the pathophysiology of neurodegenerative diseases has increasingly been recognized. Dysregulation of microglial and astrocyte properties and function has been described also in the fatal degenerative motor neuron disease amyotrophic lateral sclerosis (ALS). Microglia cells, the immune cells of the nervous system, can either have an immunonegative neurotoxic or immunopositive neuroprotective phenotype. The feverfew plant (Tanacetum parthenium) derived compound parthenolide has been found to be capable of interfering with microglial phenotype and properties. Positive treatment effects were shown in animal models of neurodegenerative diseases like Alzheimer's disease and Parkinson's disease. Now we were able to show that PTL has a modulating effect on primary mouse microglia cells, both wild type and SOD1, causing them to adopt a more neuroprotective potential. Furthermore, we were able to show that PTL, through its positive effect on microglia, also has an indirect positive impact on motor neurons, although PTL itself has no direct effect on these primary motor neurons. The results of our study give reason to consider PTL as a drug candidate for ALS.}, } @article {pmid40100796, year = {2025}, author = {Giroud, M and Kuhn, B and Steiner, S and Westwood, P and Mendel, M and Mani, A and Pinard, E and Haap, W and Grether, U and Caramenti, P and Rombach, D and Zambaldo, C and Ritter, M and Schmid, P and Gasser, C and Aregger, N and Séchet, N and Topp, A and Bilyard, M and Malnight-Alvarez, A and Plitzko, I and Hilbert, M and Kalayil, S and Burger, D and Bonardi, C and Saal, W and Haider, A and Wittwer, MB and Brigo, A and Benz, J and Keaney, J}, title = {Discovery of a Potent SARM1 Base-Exchange Inhibitor with In Vivo Efficacy.}, journal = {Journal of medicinal chemistry}, volume = {68}, number = {6}, pages = {6558-6575}, doi = {10.1021/acs.jmedchem.4c03127}, pmid = {40100796}, issn = {1520-4804}, mesh = {Animals ; *Armadillo Domain Proteins/antagonists & inhibitors/metabolism ; Mice ; *Cytoskeletal Proteins/antagonists & inhibitors/metabolism ; Humans ; Structure-Activity Relationship ; Drug Discovery ; Male ; }, abstract = {Sterile alpha and TIR Motif Containing 1 (SARM1) is a nicotinamide adenine dinucleotide (NAD[+]) hydrolase that plays a central role in programmed axonal degeneration. Axonal degeneration has been linked to neurodegenerative and neurological disorders such as multiple sclerosis, amyotrophic lateral sclerosis, Parkinson's disease, and peripheral neuropathies. Therefore, developing potent and selective SARM1 inhibitors could be an effective strategy to treat these disorders. We present herein the structure-guided discovery of two novel SARM1 inhibitors, 7 and 35. Compounds 7 and 35 are potent inhibitors across assays and possess favorable ADMET properties. When tested in vivo, compound 7 showed efficacy after oral dosing in a mouse model of peripheral nerve injury by decreasing plasma neurofilament light (NfL) levels at 50 mg/kg compared with vehicle-treated control mice, holding promise for the treatment of neurodegenerative and neurological disorders.}, } @article {pmid40100285, year = {2025}, author = {De Bertier, S and Lautrette, G and Amador, MD and Miki, T and Boillée, S and Lobsiger, CS and Bohl, D and Darios, F and Machat, S and Duchesne, M and Vourc'h, P and Fauret-Amsellem, AL and Corcia, P and Guy, N and Couratier, P and Seilhean, D and Millecamps, S}, title = {MAPT mutations in amyotrophic lateral sclerosis: clinical, neuropathological and functional insights.}, journal = {Journal of neurology}, volume = {272}, number = {4}, pages = {272}, pmid = {40100285}, issn = {1432-1459}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/pathology/physiopathology ; *tau Proteins/genetics/metabolism ; Male ; Female ; Middle Aged ; Adult ; Aged ; *Mutation/genetics ; Brain/pathology/metabolism ; Pedigree ; Exome Sequencing ; Animals ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are part of a well-established disease continuum, underpinned by TDP43-pathology. In contrast, the clinical manifestations of Tau-linked disorders are typically limited to cognitive phenotypes or atypical parkinsonism, although few reports describe motor neuron involvement associated with MAPT (microtubule-associated protein Tau) mutations. This study aimed to investigate the contribution of MAPT to the ALS phenotype.

METHODS: We analyzed a whole-exome sequencing database comprising 470 ALS patients and explored the pathogenicity of the identified variants through familial, clinical, neuropathological, and cellular studies.

RESULTS: We identified two missense variants in the Tau repeat domains: the novel p.I308T variant, in a patient with early-onset ALS, and the p.P364S mutation in three families with spinal- or respiratory-onset ALS. Segregation of this mutation with disease could be confirmed in two affected cousins. The observation of p.P364S patient's tissue showed accumulations of hyperphosphorylated Tau in various brain regions, prominent in the motor cortex with Lewy body-like inclusions, along with a C-terminal cleaved form of Tau in muscle. In NSC-34 motor neuron cells expressing p.I308T or p.P364S mutants, Tau was discontinuous along the neurites, with clusters of mitochondria resulting from impaired mitochondrial motility.

CONCLUSION: These findings expand the molecular understanding of ALS to include MAPT mutations. MAPT analysis should be incorporated into ALS genetic screening, particularly in patients with a familial history of the disease. Recognizing the full spectrum of MAPT-linked neurodegenerative diseases is of considerable interest, given the ongoing efforts to develop MAPT-targeted therapies.}, } @article {pmid40099869, year = {2025}, author = {Kim, SB and Lee, JS and Lan, X and Huang, W and Taylor, DJ and Kwon, YT and Zhang, Y and Ji, CH}, title = {The structure-function relationship of ATE1 R-transferase of the autophagic Arg/N-degron pathway.}, journal = {Autophagy}, volume = {}, number = {}, pages = {1-3}, doi = {10.1080/15548627.2025.2473393}, pmid = {40099869}, issn = {1554-8635}, support = {R35 GM150678/GM/NIGMS NIH HHS/United States ; }, abstract = {ATE1 (arginyltransferase 1; EC 2.3.2) transfers the amino acid arginine (Arg) from Arg-tRNA[Arg] to the N-terminal (Nt) residues of proteins, such as aspartate (Asp), glutamate (Glu), and oxidized cysteine (Cys). The resulting Nt-Arg acts as an N-degron that regulates the degradation of various biomaterials via the ubiquitin/Ub-proteasome system (UPS) or the autophagy-lysosome system (ALS). In the UPS, Arg/N-degrons are recognized by cognate N-recognins, leading to substrate ubiquitination and proteasomal degradation. In the ALS, the same degrons bind the macroautophagy/autophagy receptor SQSTM1/p62 (sequestosome 1) to facilitate self-polymerization of SQSTM1 associated with cargoes and SQSTM1 interaction with LC3-II on phagophores. A key unresolved question is why only a small subset of proteins acquires Arg/N-degrons, given the rather weak binding affinity of ATE1 for Nt-substrates. In this study, we determined the cryo-EM structures of human ATE1 in complex with Arg-tRNA[Arg] and an Nt-Asp peptide. ATE1 harbors two adjacent pockets that each bind an Nt-substrate or Arg-tRNA[Arg], the latter being wrapped by a long, unstructured loop. In the apo state, two ATE1 monomers form a homodimer. ATE1 achieves the selectivity for its peptidyl-ligands through these multivalent interactions, with Kd values in the micro-molar range. These results reveal the structural principle of Nt-arginylation at the crossroads of the UPS and ALS.Abbreviations: ALS: autophagy-lysosome system; Arg: arginine; Asp: aspartate; ATE1: arginyltransferase 1; Cys: cysteine; CysO2(H): Cys sulfinic acid; Glu: glutamate; Nt: N-terminal; UBR: ubiquitin protein ligase E3 component n-recognin; UPS: ubiquitin-proteasome system; ZZ: ZZ-type zinc finger.}, } @article {pmid40099804, year = {2025}, author = {Zheng, W and Zhang, X and Chen, J and Luan, X and Wang, J and Zhang, L and Liu, K and Zhao, Y and Xu, Z}, title = {The Effect of Repetitive Transcranial Magnetic Stimulation of the Dorsolateral Prefrontal Cortex on the Amyotrophic Lateral Sclerosis Patients With Cognitive Impairment: A Double-Blinded, Randomized, and Sham Control Trial.}, journal = {CNS neuroscience & therapeutics}, volume = {31}, number = {3}, pages = {e70316}, pmid = {40099804}, issn = {1755-5949}, support = {20YF1436400//Shanghai Sailing program/ ; 23DZ2291500//Shanghai Science and Technology Innovation Action Plan/ ; }, mesh = {Humans ; Double-Blind Method ; Male ; Female ; *Amyotrophic Lateral Sclerosis/therapy/complications/psychology ; *Transcranial Magnetic Stimulation/methods ; Middle Aged ; *Cognitive Dysfunction/therapy/etiology/psychology ; Aged ; *Dorsolateral Prefrontal Cortex/physiology ; Treatment Outcome ; Adult ; *Prefrontal Cortex ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease. A large number of ALS patients have cognitive impairment. In this double-blinded, randomized, and sham-controlled study, we aimed to investigate the effect of repetitive transcranial magnetic stimulation (rTMS) on ALS patients with cognitive impairment.

METHODS: A total of 90 ALS patients with cognitive impairment were recruited from two cohorts; 80 participants were randomly assigned in a 1:1 ratio to receive 10 Hz rTMS or sham treatment on the bilateral dorsolateral prefrontal cortices (DLPFC) for 4 consecutive weeks. The patients were assessed by ECAS and ALSFRS-R scales. The Zarit care burden scale was administered to caregivers of ALS patients. The primary outcome measured was the rate of decline in the total ECAS score between pretreatment, 6 months post-treatment, and 12 months post-treatment. Secondary outcomes included the group difference in the slope of the Zarit score, ALSFRS-R total score, and the neurofilament light chain plasma levels.

RESULTS: The ECAS total score in the intention-to-treat population significantly changed from 79.74 ± 6.39 to 81.98 ± 6.51 and 79.22 ± 6.50 with rTMS intervention at the 6-month and 12-month follow-ups, respectively (p = 0.031, p = 0.042). The Zarit score also significantly decreased from 57.65 ± 3.42 to 52.24 ± 3.34 and 56.42 ± 3.41 at the 3-month and 6-month post-treatment time points, respectively (p = 0.003, p = 0.014). No significant differences were observed between the groups for other secondary endpoints. However, there was a trend of decreasing NF-L level rates in the treatment group over the first 6 months' follow-up.

CONCLUSIONS: rTMS could yield short-term positive effects on the ALS patients subgroup with cognitive impairment and alleviate caregivers' burden. No improvement was observed in the severity of ALS and ALS plasma biomarkers.}, } @article {pmid40099353, year = {2025}, author = {Giorgio, CM and Tancredi, V and Licata, G and Moscarella, E and Argenziano, G and Fulgione, E and Babino, G and Franzese, P and Di Brizzi, EV}, title = {Cutting-edge insights: LC-OCT and 5% cyclosporine for early lichen sclerosus treatment.}, journal = {Dermatology reports}, volume = {}, number = {}, pages = {}, doi = {10.4081/dr.2025.10279}, pmid = {40099353}, issn = {2036-7392}, abstract = {Dear Editor, Atrophic lichen sclerosus (ALS) is a chronic inflammatory dermatosis with significant morbidity, primarily affecting genital areas. The disease is often misdiagnosed or underdiagnosed, resulting in delayed treatment and progression to atrophic stages and permanent scars. While corticosteroids remain the first-line treatment, their long-term use may lead to adverse effects such as skin atrophy, prompting the need for alternative therapies. Cyclosporine, a calcineurin inhibitor, has shown efficacy in managing immune-mediated skin diseases and is delivered effectively through the Pentravan® vehicle. [...].}, } @article {pmid40099231, year = {2025}, author = {Hwang, DW and Ser, J and Ziabrev, K and Park, GK and Jo, MJ and Yokomizo, S and Bao, K and Yamashita, A and Cho, H and Henary, M and Kashiwagi, S and Choi, HS}, title = {Image-Guided Monitoring of Mitochondria and Blood-Brain Barrier Dysfunction in Amyotrophic Lateral Sclerosis Mice.}, journal = {Biomaterials research}, volume = {29}, number = {}, pages = {0162}, pmid = {40099231}, issn = {1226-4601}, abstract = {Early detection of amyotrophic lateral sclerosis (ALS) progression is critical for improving disease management and therapeutic outcomes. However, the clinical heterogeneity and variability in ALS symptoms often lead to delayed diagnosis and suboptimal therapeutic interventions. Since mitochondrial dysfunction is a hallmark of ALS, we hypothesized that monitoring mitochondrial function could serve as a reliable strategy for early diagnosis and therapeutic monitoring of ALS. To address this, we synthesized and characterized 2 novel near-infrared fluorophores, ALS04 and ALS05, designed to target mitochondria and lysosomes. Their physicochemical properties, serum protein binding, fluorescence characteristics, photostability, and pharmacokinetics were systematically evaluated. We found that benzothiazole-based fluorophores exhibit excellent mitochondrial targeting, optimal optical properties, biocompatibility, and favorable biodistribution in vivo. Interestingly, ALS04 showed superior mitochondrial accumulation compared to ALS05, despite their similar physicochemical properties. This enhanced accumulation can be attributed to the lower molecular weight and higher lipophilicity of ALS04. Real-time fluorescence imaging revealed a substantial reduction in ALS04 signals in mitochondrial-rich tissues such as brown fat, highlighting its potential for monitoring mitochondrial dysfunction in early-stage ALS. Furthermore, the detection of ALS04 in the mouse brain suggests its ability to monitor blood-brain barrier hyperpermeability, another key feature of ALS pathology. These findings establish ALS04 as a promising noninvasive imaging tool for monitoring biomarkers associated with ALS progression. Its ability to detect early-stage pathophysiological changes in an ALS mouse model highlights its potential for advancing our understanding of ALS mechanisms and facilitating the identification of novel therapeutic targets.}, } @article {pmid40097890, year = {2025}, author = {Dezfouli, MA and Shalilahmadi, D and Shamsaei, G and Esmaeili, A and Majdinasab, N and Rashidi, SK}, title = {Circulating miR-223/NLRP3 axis and IL-1β level in functional disease progression of amyotrophic lateral sclerosis.}, journal = {Acta neurologica Belgica}, volume = {125}, number = {3}, pages = {783-791}, pmid = {40097890}, issn = {2240-2993}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/blood/physiopathology ; *NLR Family, Pyrin Domain-Containing 3 Protein/blood ; Male ; Female ; *Interleukin-1beta/blood ; Middle Aged ; *MicroRNAs/blood ; *Disease Progression ; Aged ; Biomarkers/blood ; Adult ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease identified by progressive motor neuron loss. NLRP3 inflammasomes induce inflammation and pyroptosis, which can lead to neurodegeneration, muscle atrophy, and respiratory decline. miR-223 targets NLRP3 and suppresses inflammasome formation. Here, miR-223, NLRP3 and IL-1β levels were evaluated as plasma biomarkers in the incidence and progression of ALS.

METHODS: 32 ALS patients and 32 healthy subjects were assessed. In all patients, the functional disability was determined by Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R), and the respiratory dysfunction was assessed by the percent predicted forced vital capacity (ppFVC) index in spirometry examination. Plasma levels of miR-223, NLRP3 and IL-1β were assessed in ALS and control groups.

RESULTS: Compared to the healthy controls, ALS patients showed decreased miR-223 expression (P < 0.0001), increased NLRP3 expression (P = 0.0002) and increased IL-1β level (P = 0.0003). The areas under the ROC curves for miR-223, NLRP3 and IL-1β were 0.82, 0.76 and 0.75 respectively. The ALSFRS-R and ppFVC values were positively correlated with miR-223 and negatively correlated with NLRP3 and IL-1β levels.

CONCLUSION: Our results indicated that changes in miR-223, NLRP3 and IL-1β levels may correlate with the occurrence and functional progression of ALS. Additionally, therapeutic approaches based on miR-223 and inflammatory mediators can be proposed as effective strategies against disease progression.}, } @article {pmid40097762, year = {2025}, author = {Nabakhteh, S and Lotfi, A and Afsartaha, A and Khodadadi, ES and Abdolghaderi, S and Mohammadpour, M and Shokri, Y and Kiani, P and Ehtiati, S and Khakshournia, S and Khatami, SH}, title = {Nutritional Interventions in Amyotrophic Lateral Sclerosis: From Ketogenic Diet and Neuroprotective Nutrients to the Microbiota-Gut-Brain Axis Regulation.}, journal = {Molecular neurobiology}, volume = {62}, number = {7}, pages = {9216-9239}, pmid = {40097762}, issn = {1559-1182}, mesh = {*Amyotrophic Lateral Sclerosis/diet therapy/microbiology ; Humans ; *Diet, Ketogenic/methods ; *Gastrointestinal Microbiome/physiology ; *Neuroprotective Agents/therapeutic use/pharmacology ; Animals ; *Brain/metabolism ; *Nutrients/therapeutic use ; *Neuroprotection ; *Brain-Gut Axis/physiology ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a complex neurodegenerative disease with significant challenges in diagnosis and treatment. Recent research has highlighted the complex nature of ALS, encompassing behavioral impairments in addition to its neurological manifestations. While several medications have been approved to slow disease progression, ongoing research is focused on identifying new therapeutic targets. The current review focuses on emerging therapeutic strategies and personalized approaches aimed at improving patient outcomes. Recent advancements highlight the importance of targeting additional pathways such as mitochondrial dysfunction and neuroinflammation to develop more effective treatments. Personalized medicine, including genetic testing and biomarkers, is proving valuable in stratifying patients and tailoring treatment options. Complementary therapies, such as nutritional interventions like the ketogenic diet and microbiome modulation, also show promise. This review emphasizes the need for a multidisciplinary approach that integrates early diagnosis, targeted treatments, and supportive care to address the multisystemic nature of ALS and improve the quality of life for patients.}, } @article {pmid40097438, year = {2025}, author = {Ayyadurai, VAS and Deonikar, P and Kamm, RD}, title = {A molecular systems architecture of neuromuscular junction in amyotrophic lateral sclerosis.}, journal = {NPJ systems biology and applications}, volume = {11}, number = {1}, pages = {27}, pmid = {40097438}, issn = {2056-7189}, mesh = {*Amyotrophic Lateral Sclerosis/metabolism/pathology/physiopathology ; Humans ; *Neuromuscular Junction/metabolism/pathology/physiopathology ; Motor Neurons/metabolism/pathology ; Animals ; Schwann Cells/metabolism ; Muscle, Skeletal/pathology/metabolism ; }, abstract = {A molecular systems architecture is presented for the neuromuscular junction (NMJ) in order to provide a framework for organizing complexity of biomolecular interactions in amyotrophic lateral sclerosis (ALS) using a systematic literature review process. ALS is a fatal motor neuron disease characterized by progressive degeneration of the upper and lower motor neurons that supply voluntary muscles. The neuromuscular junction contains cells such as upper and lower motor neurons, skeletal muscle cells, astrocytes, microglia, Schwann cells, and endothelial cells, which are implicated in pathogenesis of ALS. This molecular systems architecture provides a multi-layered understanding of the intra- and inter-cellular interactions in the ALS neuromuscular junction microenvironment, and may be utilized for target identification, discovery of single and combination therapeutics, and clinical strategies to treat ALS.}, } @article {pmid40097075, year = {2025}, author = {Cuevas, EP and Madruga, E and Valenzuela-Martínez, I and Ramírez, D and Gil, C and Nagaraj, S and Martin-Requero, A and Martinez, A}, title = {MicroRNA signature of lymphoblasts from amyotrophic lateral sclerosis patients as potential clinical biomarkers.}, journal = {Neurobiology of disease}, volume = {208}, number = {}, pages = {106871}, doi = {10.1016/j.nbd.2025.106871}, pmid = {40097075}, issn = {1095-953X}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/metabolism/diagnosis ; *MicroRNAs/metabolism/genetics ; Biomarkers/metabolism ; Middle Aged ; Female ; *Lymphocytes/metabolism ; Male ; Aged ; Superoxide Dismutase-1/genetics ; Adult ; High-Throughput Nucleotide Sequencing ; }, abstract = {MicroRNAs (miRNAs) are a class of small, non-coding RNAs involved in different cellular functions that have emerged as key regulators of neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS). ALS is a fatal disease that lacks of not only effective treatments, but also presents delays in its diagnosis, since reliable clinical biomarkers are unavailable. In recent years, advancements in high-throughput sequencing strategies have led to the identification of novel ALS biomarkers, facilitating earlier diagnosis and assessment of treatment efficacy. Since immortalized lymphocytes obtained from peripheral blood are a suitable model to study pathological features of ALS, we employed these samples with the aim of characterize the dysregulated miRNAs in ALS patients. Next-generation sequencing (NGS) was utilized in order to analyze the expression profiles of miRNAs in immortalized lymphocytes from healthy controls, sporadic ALS (sALS), and familial ALS with mutations in superoxide dismutase 1 (SOD1-ALS). The screening analysis of the NGS data identified a set of dysregulated miRNAs, of which nine candidates were selected for qRT-PCR validation, identifying for the first time the possible importance of hsa-miR-6821-5p as a potential ALS biomarker. Furthermore, the up-regulated miRNAs identified are predicted to have direct or indirect interactions with genes closely related to ALS, such as SIGMAR1, HNRNPA1 and TARDBP. Additionally, by Metascape enrichment analysis, we found the VEGFA/VEGFR2 signaling pathway, previously implicated in neuroprotective effects in ALS, as a candidate pathway for further analyses.}, } @article {pmid40095345, year = {2025}, author = {Dehghani, S and Ocakcı, O and Hatipoglu, PT and Özalp, VC and Tevlek, A}, title = {Exosomes as Biomarkers and Therapeutic Agents in Neurodegenerative Diseases: Current Insights and Future Directions.}, journal = {Molecular neurobiology}, volume = {62}, number = {7}, pages = {9190-9215}, pmid = {40095345}, issn = {1559-1182}, mesh = {*Exosomes/metabolism ; Humans ; *Neurodegenerative Diseases/therapy/diagnosis/metabolism/drug therapy ; *Biomarkers/metabolism ; Animals ; Blood-Brain Barrier/metabolism ; Drug Delivery Systems ; }, abstract = {Neurodegenerative diseases (NDs) like Alzheimer's, Parkinson's, and ALS rank among the most challenging global health issues, marked by substantial obstacles in early diagnosis and effective treatment. Current diagnostic techniques frequently demonstrate inadequate sensitivity and specificity, whilst conventional treatment strategies encounter challenges related to restricted bioavailability and insufficient blood-brain barrier (BBB) permeability. Recently, exosomes-nanoscale vesicles packed with proteins, RNAs, and lipids-have emerged as promising agents with the potential to reshape diagnostic and therapeutic approaches to these diseases. Unlike conventional drug carriers, they naturally traverse the BBB and can deliver bioactive molecules to affected neural cells. Their molecular cargo can influence cell signaling, reduce neuroinflammation, and potentially slow neurodegenerative progression. Moreover, exosomes serve as non-invasive biomarkers, enabling early and precise diagnosis while allowing real-time disease monitoring. Additionally, engineered exosomes, loaded with therapeutic molecules, enhance this capability by targeting diseased neurons and overcoming conventional treatment barriers. By offering enhanced specificity, reduced immunogenicity, and an ability to bypass physiological limitations, exosome-based strategies present a transformative advantage over existing diagnostic and therapeutic approaches. This review examines the multifaceted role of exosomes in NDDs, emphasizing their diagnostic capabilities, intrinsic therapeutic functions, and transformative potential as advanced treatment vehicles.}, } @article {pmid40094392, year = {2025}, author = {Resch, M and Frickel, JS and Dischinger, K and Choo, RSW and Hell, K and Harner, ME}, title = {The Mia40 substrate Mix17 exposes its N-terminus to the cytosolic side of the mitochondrial outer membrane.}, journal = {Journal of cell science}, volume = {138}, number = {9}, pages = {}, pmid = {40094392}, issn = {1477-9137}, support = {413985647//Deutsche Forschungsgemeinschaft/ ; //LMUexcellent/ ; //Ludwig-Maximilians-Universität München/ ; }, mesh = {*Mitochondrial Membranes/metabolism ; *Saccharomyces cerevisiae Proteins/metabolism/genetics/chemistry ; *Saccharomyces cerevisiae/metabolism/genetics ; Mitochondrial Precursor Protein Import Complex Proteins ; *Cytosol/metabolism ; *Mitochondrial Membrane Transport Proteins/metabolism/genetics ; Humans ; Mitochondria/metabolism ; *Mitochondrial Proteins/metabolism/genetics ; }, abstract = {Mitochondrial architecture and the contacts between the mitochondrial outer and the inner membranes depend on the mitochondrial contact site and cristae-organizing system (MICOS) that is highly conserved from yeast to human. Variants in the mammalian MICOS subunit Mic14 (also known as CHCHD10) have been linked to amyotrophic lateral sclerosis and frontotemporal dementia, indicating the importance of this protein. Mic14 has a yeast ortholog, Mix17, a protein of unknown function, which has not been shown to interact with MICOS so far. As a first step to elucidate the function of Mix17 and its orthologs, we analyzed its interactions, biogenesis and mitochondrial sublocation. We report that Mix17 is not a stable MICOS subunit in yeast. Our data suggest that Mix17 is the first Mia40 substrate in the mitochondrial outer membrane. Unlike all other Mia40 substrates, Mix17 spans the mitochondrial outer membrane and exposes its N-terminus to the cytosol. The insertion of Mix17 into the mitochondrial outer membrane is likely to be mediated by its interaction with Tom40, the pore of the TOM complex. Moreover, we show that the exposure of Mix17 to the cytosolic side of the mitochondrial membrane depends on its N-terminus.}, } @article {pmid40093130, year = {2025}, author = {Zhou, Z and Luquette, LJ and Dong, G and Kim, J and Ku, J and Kim, K and Bae, M and Shao, DD and Sahile, B and Miller, MB and Huang, AY and Nathan, WJ and Nussenzweig, A and Park, PJ and Lagier-Tourenne, C and Lee, EA and Walsh, CA}, title = {Recurrent patterns of widespread neuronal genomic damage shared by major neurodegenerative disorders.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {40093130}, issn = {2692-8205}, support = {R01 HG012573/HG/NHGRI NIH HHS/United States ; R56 AG079857/AG/NIA NIH HHS/United States ; DP2 AG072437/AG/NIA NIH HHS/United States ; R01 AG082346/AG/NIA NIH HHS/United States ; K01 AG051791/AG/NIA NIH HHS/United States ; R01 NS032457/NS/NINDS NIH HHS/United States ; DP2 AG086138/AG/NIA NIH HHS/United States ; R01 AG070921/AG/NIA NIH HHS/United States ; R01 AG088082/AG/NIA NIH HHS/United States ; }, abstract = {Amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and Alzheimer's disease (AD) are common neurodegenerative disorders for which the mechanisms driving neuronal death remain unclear. Single-cell whole-genome sequencing of 429 neurons from three C9ORF72 ALS, six C9ORF72 FTD, seven AD, and twenty-three neurotypical control brains revealed significantly increased burdens in somatic single nucleotide variant (sSNV) and insertion/deletion (sIndel) in all three disease conditions. Mutational signature analysis identified a disease-associated sSNV signature suggestive of oxidative damage and an sIndel process, affecting 28% of ALS, 79% of FTD, and 65% of AD neurons but only 5% of control neurons (diseased vs. control: OR=31.20, p = 2.35×10[-10]). Disease-associated sIndels were primarily two-basepair deletions resembling signature ID4, which was previously linked to topoisomerase 1 (TOP1)-mediated mutagenesis. Duplex sequencing confirmed the presence of sIndels and identified similar single-strand events as potential precursor lesions. TOP1-associated sIndel mutagenesis and resulting genome instability may thus represent a common mechanism of neurodegeneration.}, } @article {pmid40092960, year = {2025}, author = {Liu, Y and Li, XF}, title = {Characteristics and therapeutic strategies for familial gastrointestinal stromal tumors.}, journal = {World journal of gastrointestinal oncology}, volume = {17}, number = {3}, pages = {100463}, pmid = {40092960}, issn = {1948-5204}, abstract = {This editorial discusses Wang et al's article on familial gastrointestinal stromal tumors (GISTs). We read with great interest this article concerning the diagnosis, treatment, and post-treatment management of patients with familial GISTs. The actual incidence of GISTs may be underestimated due to diagnostic limitations and the long-term low-risk behavior of some GISTs. The molecular landscape of GISTs is primarily driven by mutations in the KIT and platelet-derived growth factor receptor alpha (PDGFRA) genes. A subset of GISTs without these mutations known as wild-type GISTs, may harbor other rare mutations, impacting their response to targeted therapies. Clinically, patients with GISTs present with non-specific symptoms, often leading to delayed diagnosis. Genetic predispositions in familial GISTs provide insights into the genetic architecture and extragastrointestinal manifestations of GISTs. Management has evolved from surgical interventions to molecular-based therapies using tyrosine kinase inhibitors. The management of GISTs, especially in familial cases, requires a multidisciplinary approach. Cases of different gene mutations were reported in the same family, suggesting that incorporating genetic testing into routine clinical practice is crucial for the early identification of high-risk individuals and the implementation of tailored surveillance programs.}, } @article {pmid40092497, year = {2025}, author = {Fujii, Y and Kanbayashi, T and Takahashi, K and Hamada, Y and Kobayashi, S and Sonoo, M}, title = {Correlation between decremental responses in repetitive nerve stimulation and disease progression rate in patients with amyotrophic lateral sclerosis.}, journal = {Clinical neurophysiology practice}, volume = {10}, number = {}, pages = {40-46}, pmid = {40092497}, issn = {2467-981X}, abstract = {OBJECTIVE: Decrement responses in repetitive nerve stimulation (RNS) are theoretically expected to correlate with the disease progression speed in amyotrophic lateral sclerosis (ALS). However, actual results have been controversial. We investigated this issue using ΔFS calculated from the ALS functional rating scale revised version (ALSFRS-R) and the duration of illness.

METHODS: RNS results of the abductor pollicis brevis, trapezius, and deltoid muscles in our previous study were reviewed. We investigated correlations and multiple regressions regarding decremental percentage (Decr%), the amplitude of the initial compound muscle action potential (Amp), and progression speed parameters, i.e. ΔFS or ΔUL-FS, the latter being the ΔFS for the upper-limb questions in ALSFRS-R.

RESULTS: Included subjects were 124 patients with ALS, 47 of whom were upper-limb onset. Multiple regression analyses revealed that Decr% is largely determined by Amp and that Δ FS or ΔUL-FS showed no or little contributions to Decr%.

CONCLUSIONS: Decremental responses in RNS does not predict the speed of progression of the functional impairment in patients with ALS.

SIGNIFICANCE: This study suggests that the decremental responses in RNS in ALS are contributed by the impaired neuromuscular transmission in chronic sprouts following extensive reinnervation, as well as by the immature sprouts.}, } @article {pmid40092496, year = {2025}, author = {Theuriet, J and Bohic, A and Bonjour, M and Bernard, E and Cluse, F and Svahn, J and Jomir, L and Vallet, AE and Demia, M and Roux, L and Bârsan, IC and Alves, L and Dion, M and Meens, L and Moussy, M and Bouhour, F and Péréon, Y and Pegat, A}, title = {Contralateral R1 response in blink reflex in patients with amyotrophic lateral sclerosis.}, journal = {Clinical neurophysiology practice}, volume = {10}, number = {}, pages = {47-51}, pmid = {40092496}, issn = {2467-981X}, abstract = {OBJECTIVE: This study aimed to compare the frequency of blink reflex's contralateral R1 responses (R1') between patients with amyotrophic lateral sclerosis (ALS), non-ALS motor deficit patients, and healthy volunteers.

METHODS: A total of 120 participants were prospectively recruited: 40 with ALS, 40 with a non-ALS motor deficit, and 40 healthy volunteers. Blink reflexes were recorded from orbicularis oculi muscles following supraorbital nerve stimulation.

RESULTS: R1' was more frequent in the ALS group (42.5 %) compared to healthy volunteers (12.5 %, p = 0.00588), and compared to non-ALS patients (7.5 %, p = 0.000789). Bilateral R1' was observed only in ALS patients (22.5 %). No clinically significant difference was found in the latencies or amplitudes of the R1, R2, or R1' responses among groups. R1' was more frequent in ALS patients with pseudobulbar affect (71.4 %) compared to those without (36.4 %).

CONCLUSIONS: The higher frequency of R1' in ALS highlights its potential role in distinguishing ALS from other motor disorders. Its sensitivity was low, but bilateral R1' was specific to ALS. The higher frequency of R1' among ALS patients with pseudobulbar affect potentially reflects corticobulbar neuron degeneration.

SIGNIFICANCE: The R1', especially when bilateral, could serve as an additional diagnostic biomarker for ALS, although its clinical relevance should be considered within the broader diagnostic context.}, } @article {pmid40091916, year = {2025}, author = {Ansari, U and Wen, J and Karabala, M and Syed, B and Abed, I and Razick, DI and Lui, F}, title = {Analysis of Respiratory Muscle Strength Training in Amyotrophic Lateral Sclerosis (ALS) Patients: A Systematic Review.}, journal = {Cureus}, volume = {17}, number = {2}, pages = {e78903}, pmid = {40091916}, issn = {2168-8184}, abstract = {Respiratory muscle weakness is a significant contributor to morbidity and mortality in amyotrophic lateral sclerosis (ALS) patients. Respiratory muscle strength training (RMST) has emerged as a potential therapeutic approach to mitigate respiratory muscle weakness in ALS. Still, its efficacy and safety remain unclear due to conflicting evidence and methodological heterogeneity in existing studies. A systematic review was conducted across three databases (PubMed (United States National Library of Medicine, Bethesda, MD, USA), Embase (Elsevier, Amsterdam, Netherlands), and Cochrane Library (Cochrane, Alberta, Canada)) following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to assess the effectiveness of RMST in ALS patients. Eligible studies included comparative studies for RMST, focusing on outcomes such as maximum inspiratory pressure (MIP), maximum expiratory pressure (MEP), forced vital capacity (FVC), and ALS Functional Rating Scale (ALSFRS-R). Quality assessment was performed using the Cochrane Risk of Bias tool. This study included six studies, including 183 patients with a mean age of 58.0 years (49.6 to 63.2) and a mean follow-up time of 21.2 weeks (eight to 52). The average mean difference for ALSFRS-R (three studies), MIP (three studies), MEP (three studies), and FVC (two studies) were 2.062 (0.04 to 5.3), 2.285 (-8.145 to 10.8), 19.435 (10.86 to 21.7), and 7.23 (3.6 to 10.86), respectively. Complications related to RMST were poorly reported across studies. Secondary outcomes, such as depression scores, blood oxygen levels, and heart rate variability, showed promising trends but lacked consistency. Despite positive findings on respiratory muscle strength, RMST's efficacy in ALS management remains inconclusive. Challenges include methodological heterogeneity, limited sample sizes, and inadequate reporting of complications. Future research should focus on standardized protocols, larger sample sizes, longer follow-ups, and comprehensive assessment of adverse effects to clarify the role of RMST in ALS treatment.}, } @article {pmid40091372, year = {2025}, author = {Jaspers Focks, RJ and Helleman, J and van den Berg, LH and Visser-Meily, JM and Gaytant, MA and Wijkstra, PJ and Beelen, A}, title = {Initiating non-invasive ventilation in patients with Amyotrophic Lateral Sclerosis in The Netherlands: A centralised approach to respiratory care.}, journal = {Journal of neuromuscular diseases}, volume = {12}, number = {3}, pages = {372-381}, doi = {10.1177/22143602251319167}, pmid = {40091372}, issn = {2214-3602}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy/complications/mortality ; *Noninvasive Ventilation/methods ; Male ; Female ; Netherlands ; Middle Aged ; Retrospective Studies ; Aged ; *Respiratory Insufficiency/therapy/etiology ; Adult ; Hypercapnia/therapy/etiology ; }, abstract = {BACKGROUND: In the Netherlands a centralised approach to respiratory care for patients with Amyotrophic Lateral Sclerosis is used based on national guidelines. Patients with Amyotrophic Lateral Sclerosis are referred to one of 4 centres for Home Mechanical Ventilation.

OBJECTIVE: Our aim was to evaluate the respiratory care according to the Dutch guideline by evaluation of reasons for starting non-invasive ventilation, timing of initiating and survival in patients with Amyotrophic Lateral Sclerosis using non-invasive ventilation.

METHOD: A retrospective chart-review was performed of 323 patients, who had been referred to centres for Home Mechanical Ventilation in 2016-2018. Data collected included symptoms of hypoventilation, forced vital capacity, blood gasses, criteria for (not) initiating non-invasive ventilation, and survival. Kaplan-Meyer curves and Multivariate Cox proportional hazard regression were used in the analysis.

RESULTS: The main criteria used for initiating non-invasive ventilation were hypercapnia (77%) and the presence of orthopnea and/or dyspnoea (25%). Median survival after starting non-invasive ventilation was 11 months, and was shorter for patients with bulbar disease onset and older age. The proportion of the total disease duration that was spent on non-invasive ventilation was not significantly affected by age, sex or site of disease. Seventy nine percent of the patients who didn't start non-invasive ventilation had reached a joint decision with their caregivers and/or physicians.

CONCLUSION: Key outcomes of the Dutch centralised respiratory care approach have shown that most patients were initiated on non-invasive ventilation due to presence of hypercapnia and/or dyspnoea/orthopnea, which is according to the Dutch guidelines. Half of patients spent at least 33% of their disease duration on non-invasive ventilation. To help find the optimal criteria and timing for non-invasive ventilation it would be useful for other countries to share their key outcomes as well.}, } @article {pmid40090808, year = {2025}, author = {Rosina, M and Scaricamazza, S and Fenili, G and Nesci, V and Valle, C and Ferri, A and Paronetto, MP}, title = {Hidden players in the metabolic vulnerabilities of amyotrophic lateral sclerosis.}, journal = {Trends in endocrinology and metabolism: TEM}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.tem.2025.02.004}, pmid = {40090808}, issn = {1879-3061}, abstract = {Amyotrophic lateral sclerosis (ALS) is a complex and rapidly progressive motor neuron disorder with a fatal outcome. Despite the remarkable progress in understanding ALS pathophysiology, which has significantly contributed to clinical trial design, ALS remains a rapidly disabling and life-shortening condition. The non-motor neuron features of ALS, including nutritional status, energy expenditure, and metabolic imbalance, are increasingly gaining attention. Indeed, the bioenergetic failure and mitochondrial dysfunction of patients with ALS impact not only the high energy-demanding motor neurons but also organs and brain areas long considered irrelevant to the disease. As such, here we discuss how considering energy balance in ALS is reshaping research on this disease, opening the path to novel targetable opportunities for its treatment.}, } @article {pmid40089090, year = {2025}, author = {Men, J and Wang, X and Zhou, Y and Huang, Y and Zheng, Y and Wang, Y and Yang, S and Chen, N and Yan, N and Duan, X}, title = {Neurodegenerative diseases: Epigenetic regulatory mechanisms and therapeutic potential.}, journal = {Cellular signalling}, volume = {131}, number = {}, pages = {111715}, doi = {10.1016/j.cellsig.2025.111715}, pmid = {40089090}, issn = {1873-3913}, mesh = {Humans ; *Epigenesis, Genetic ; *Neurodegenerative Diseases/genetics/therapy/pathology ; DNA Methylation ; Animals ; Histones/metabolism ; RNA, Untranslated/genetics/metabolism ; Chromatin Assembly and Disassembly ; }, abstract = {Neurodegenerative diseases (NDDs) are a class of diseases in which the progressive loss of subtype-specific neurons leads to dysfunction. NDDs include Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS), among others. Previous studies have demonstrated that the pathogenesis of NDDs involves various mechanisms, including genetic factors, oxidative stress, apoptosis, and the immune response. Recent studies have shown that epigenetic regulation mediates the interactions between DNA methylation, chromatin remodeling, histone modification, and non-coding RNAs, thus affecting gene transcription. A growing body of research links epigenetic modifications to crucial pathways involved in the occurrence and development of NDDs. Epigenetics has also been found to regulate and maintain nervous system function, and its imbalance is closely related to the occurrence and development of NDDs. The present review summarizes focuses on the role of epigenetic modifications in the pathogenesis of NDDs and provides an overview of the key genes regulated by DNA methylation, histone modification, and non-coding RNAs in NDDs. Further, the current research status of epigenetics in NDDs is summarized and the potential application of epigenetics in the clinical diagnosis and treatment of NDDs is discussed.}, } @article {pmid40087396, year = {2025}, author = {Omar, OMF and Kimble, AL and Cheemala, A and Tyburski, JD and Pandey, S and Wu, Q and Reese, B and Jellison, ER and Hao, B and Li, Y and Yan, R and Murphy, PA}, title = {Endothelial TDP-43 depletion disrupts core blood-brain barrier pathways in neurodegeneration.}, journal = {Nature neuroscience}, volume = {28}, number = {5}, pages = {973-984}, pmid = {40087396}, issn = {1546-1726}, support = {NS074256//U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; K99 HL125727/HL/NHLBI NIH HHS/United States ; RF1 NS074256/NS/NINDS NIH HHS/United States ; GM135592//U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)/ ; RF1 AG046929/AG/NIA NIH HHS/United States ; AG046929//U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ ; RF1 NS117449/NS/NINDS NIH HHS/United States ; R01 GM135592/GM/NIGMS NIH HHS/United States ; RF1-NS117449//U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; R01 AG046929/AG/NIA NIH HHS/United States ; R00-HL125727//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; R00 HL125727/HL/NHLBI NIH HHS/United States ; 23PRE1027078//American Heart Association (American Heart Association, Inc.)/ ; R01 NS074256/NS/NINDS NIH HHS/United States ; 19IPLOI34770151//American Heart Association (American Heart Association, Inc.)/ ; }, mesh = {Humans ; *Blood-Brain Barrier/metabolism/pathology ; *DNA-Binding Proteins/genetics/metabolism/deficiency ; Male ; Female ; Middle Aged ; Aged ; Animals ; Adult ; Aged, 80 and over ; *Neurodegenerative Diseases/pathology/metabolism ; Mice ; *Endothelial Cells/metabolism/pathology ; Young Adult ; Microglia/metabolism ; Alzheimer Disease/pathology/metabolism ; }, abstract = {Endothelial cells (ECs) help maintain the blood-brain barrier but deteriorate in many neurodegenerative disorders. Here we show, using a specialized method to isolate EC and microglial nuclei from postmortem human cortex (92 donors, 50 male and 42 female, aged 20-98 years), that intranuclear cellular indexing of transcriptomes and epitopes enables simultaneous profiling of nuclear proteins and RNA transcripts at a single-nucleus resolution. We identify a disease-associated subset of capillary ECs in Alzheimer's disease, amyotrophic lateral sclerosis and frontotemporal degeneration. These capillaries exhibit reduced nuclear β-catenin and β-catenin-downstream genes, along with elevated TNF/NF-κB markers. Notably, these transcriptional changes correlate with the loss of nuclear TDP-43, an RNA-binding protein also depleted in neuronal nuclei. TDP-43 disruption in human and mouse ECs replicates these alterations, suggesting that TDP-43 deficiency in ECs is an important factor contributing to blood-brain barrier breakdown in neurodegenerative diseases.}, } @article {pmid40086112, year = {2025}, author = {Liampas, I and Veltsista, D and Germeni, A and Batzikosta, P and Michou, E and Kefalopoulou, Z and Chroni, E}, title = {F waves in amyotrophic lateral sclerosis: A systematic review and meta-analysis.}, journal = {Neurophysiologie clinique = Clinical neurophysiology}, volume = {55}, number = {4}, pages = {103061}, doi = {10.1016/j.neucli.2025.103061}, pmid = {40086112}, issn = {1769-7131}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology/diagnosis ; *Neural Conduction/physiology ; Ulnar Nerve/physiopathology ; Electromyography ; Muscle, Skeletal/physiopathology ; }, abstract = {OBJECTIVE: This systematic review and meta-analysis aimed to determine the pattern of F-wave abnormalities and their potential utility in the early diagnosis of amyotrophic lateral sclerosis (ALS).

METHODS: Medline and Embase were thoroughly searched. We primarily emphasized F-wave recordings from the abductor digiti minimi, following stimulation of the ulnar nerve at the wrist. Data from case-control studies involving individuals with ALS versus healthy controls (HC) or other well-defined patient groups were reviewed and -if appropriate- quantitatively synthesized.

RESULTS: Twenty-nine studies were included in this systematic review and 17 of them in the analytic part. The pattern of F-abnormalities in ALS compared to HC was as follows: decreased persistence (MD=20.25 %,15.67-24.84 %), mildly prolonged minimum latency (MD=1.59msec,1.11-2.06msec), increased maximum amplitude (MD=196μV,106-287μV) and elevated Index total Freps (MD=33.9 %,26.0-41.8 %). Affected limbs (with substantial weakness in clinical examination and/or muscle wasting and/or abnormal nerve conduction studies) exhibited more marked abnormalities in persistence, minimum latency, and Index total Freps, whereas abnormalities in these parameters were very mild in clinically unaffected limbs. More prominent increases in maximum amplitude accompanied pyramidal dysfunction. Of note, isolated upper motor neuron (UMN) disorders exhibited a comparable increase in Index total Freps without a decrease in persistence.

CONCLUSIONS: The pattern of F wave abnormalities may raise suspicion of involvement of the under-study lower motor neuron (LMN) pool in ALS. These findings may identify LMN dysfunction even at a preclinical stage and prompt extensive electromyographic investigations. UMN involvement may to some extent differentiate the profile of F wave abnormalities in ALS.}, } @article {pmid40085521, year = {2025}, author = {Mercan, M and Seyhan, S and Yayla, V}, title = {The phenotyping dilemma in VRK1-related motor neuron disease: a Turkish family with young-onset amyotrophic lateral sclerosis caused by a novel mutation.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {26}, number = {5-6}, pages = {573-590}, doi = {10.1080/21678421.2025.2477732}, pmid = {40085521}, issn = {2167-9223}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/diagnostic imaging ; Male ; Turkey ; Female ; Phenotype ; Adult ; Pedigree ; *Intracellular Signaling Peptides and Proteins/genetics ; *Protein Serine-Threonine Kinases/genetics ; Middle Aged ; *Mutation/genetics ; Age of Onset ; *Motor Neuron Disease/genetics ; Exome Sequencing ; Mutation, Missense/genetics ; Magnetic Resonance Imaging ; }, abstract = {Objective: Vaccinia-related kinase 1 (VRK1)-related disease is an extremely rare autosomal recessive disorder primarily affecting the peripheral and/or central nervous system. In this report, we describe the genetic and clinical features of two siblings from a Turkish family presenting with an amyotrophic lateral sclerosis (ALS) phenotype due to a novel homozygous VRK1 mutation, and discuss the broad phenotypic spectrum associated with pathogenic variants in this gene. Methods: We analyzed the demographic data, clinical histories, neurological examinations, laboratory findings, and genetic results of 53 patients, including our cases, derived from 27 different reports. Results: Whole-exome sequencing identified a novel homozygous missense mutation, c.700A > G (p.Asn234Asp), in the VRK1 gene in two affected siblings. The characteristic features of the ALS phenotype included a recessive inheritance pattern, motor deficits with onset in the lower limbs, pyramidal tract signs, and a muscle magnetic resonance imaging (MRI) pattern demonstrating preferential involvement of the posterior compartments of the leg and thigh. The most common phenotypes associated with VRK1 mutations were ALS (18/53, 34%) and distal hereditary motor neuropathy (dHMN) (14/53, 26.4%), followed by pontocerebellar hypoplasia type 1 (7/53, 13.2%), hereditary motor and sensory neuropathy (5/53, 9.4%), autosomal recessive primary microcephaly with brain malformations (4/53, 7.5%), and spastic paraplegia (2/53, 3.8%). The ALS phenotype exhibited a significantly earlier mean age of onset compared to the dHMN phenotype (p = 0.015; 15.3 ± 11.5 and 27 ± 15.5 years, respectively). Conclusion: Our findings highlight the importance of investigating VRK1 mutations in patients with young-onset familial ALS. Furthermore, this report provides a systematic classification of the phenotype definitions associated with VRK1 mutations.}, } @article {pmid40084393, year = {2025}, author = {Helmold, B and Nathaniel, G and Barkhaus, P and Bertorini, T and Bromberg, M and Brown, A and Carter, GT and Chang, V and Crayle, J and Denson, K and Glass, J and Heiman-Patterson, T and Hobson, E and Jackson, C and Jhooty, S and Mallon, E and Maragakis, N and Cadavid, JM and Mcdermott, C and Pattee, G and Pierce, K and Wang, O and Wicks, P and Bedlack, R}, title = {ALSUntangled #78: Zinc.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {26}, number = {5-6}, pages = {599-603}, doi = {10.1080/21678421.2025.2476688}, pmid = {40084393}, issn = {2167-9223}, mesh = {*Amyotrophic Lateral Sclerosis/drug therapy/diet therapy ; Humans ; *Zinc/therapeutic use/administration & dosage ; *Dietary Supplements ; Animals ; Disease Progression ; }, abstract = {ALSUntangled reviews alternative and off-label treatments for people living with amyotrophic lateral sclerosis (PALS). In this review, we assess the utilization of dietary zinc supplements for modulating ALS pathology and progression. Studies in mouse models of ALS have demonstrated that high-dose zinc supplementation may be harmful, but moderate doses could potentially be beneficial. Clinical data is limited, and only one trial has explored zinc supplementation within PALS. This study reported potential benefits in slowing ALS progression but lacked statistical analyses and failed to report quantitative evidence. Numerous case reports from individual patients at varying doses have demonstrated no benefit. Zinc supplements at moderate doses are generally low cost and not associated with severe complications, but further research is required to determine the safety and efficacy of zinc supplementation within PALS. Therefore, we cannot at this time, endorse zinc supplementation to slow ALS progression.}, } @article {pmid40080233, year = {2025}, author = {Aydın, Ş and Özdemir, S and Adıgüzel, A}, title = {The Potential of cfDNA as Biomarker: Opportunities and Challenges for Neurodegenerative Diseases.}, journal = {Journal of molecular neuroscience : MN}, volume = {75}, number = {1}, pages = {34}, pmid = {40080233}, issn = {1559-1166}, mesh = {Humans ; Biomarkers/blood ; *Neurodegenerative Diseases/diagnosis/genetics/blood ; *Cell-Free Nucleic Acids/blood/metabolism ; Animals ; }, abstract = {Neurodegenerative disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS), are characterized by the progressive and gradual degeneration of neurons. The prevalence and rates of these disorders rise significantly with age. As life spans continue to increase in many countries, the number of cases is expected to grow in the foreseeable future. Early and precise diagnosis, along with appropriate surveillance, continues to pose a challenge. The high heterogeneity of neurodegenerative diseases calls for more accurate and definitive biomarkers to improve clinical therapy. Cell-free DNA (cfDNA), including fragmented DNA released into bodily fluids via apoptosis, necrosis, or active secretion, has emerged as a promising non-invasive diagnostic tool for various disorders including neurodegenerative diseases. cfDNA can serve as an indicator of ongoing cellular damage and mortality, including neuronal loss, and may provide valuable insights into disease processes, progression, and therapeutic responses. This review will first cover the key aspects of cfDNA and then examine recent advances in its potential use as a biomarker for neurodegenerative disorders.}, } @article {pmid40077653, year = {2025}, author = {de Carvalho Vilar, MD and Coutinho, KMD and de Lima Vale, SH and Dourado Junior, MET and de Medeiros, GCBS and Piuvezam, G and Brandao-Neto, J and Leite-Lais, L}, title = {Evidence-Based Nutritional Recommendations for Maintaining or Restoring Nutritional Status in Patients with Amyotrophic Lateral Sclerosis: A Systematic Review.}, journal = {Nutrients}, volume = {17}, number = {5}, pages = {}, pmid = {40077653}, issn = {2072-6643}, support = {grant number 302298/2017-7 (Jose Brandao-Neto)//National Council for Scientific and Technological Development/ ; TED 132/2018//Ministry of Health (Brazil) - Laboratory of Technological Innovation in Health from the Federal University of Rio Grande do Norte - LAIS/UFRN/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diet therapy/therapy/physiopathology/complications ; *Nutritional Status ; Evidence-Based Medicine ; Nutrition Assessment ; Quality of Life ; Deglutition Disorders/etiology ; Dietary Supplements ; *Nutritional Support ; *Nutrition Therapy ; Practice Guidelines as Topic ; Gastrostomy ; }, abstract = {Background/Objectives: This study is a systematic review of guidelines that aims to synthesize evidence-based recommendations to support appropriate nutritional management for patients with amyotrophic lateral sclerosis (ALS). Methods: PubMed/MEDLINE, Embase, Scopus, SciELO, Web of Science, LILACS, ScienceDirect, and Google Scholar were searched for records published up to July 2024. Clinical practice guidelines addressing any aspect of nutritional intervention in ALS were included. No language or country of publication restrictions were applied. Data extraction was performed by two independent reviewers. The methodological quality of the reports was assessed using the AGREE II instrument. Discrepancies were resolved by consensus. Results: The findings and main recommendations were summarized narratively. A total of 837 records were identified, and 11 were included in this review. The overall AGREE II scores for the included studies ranged from 3 to 7. The summary of nutritional recommendations was organized into topics: (1) dysphagia, (2) nutritional assessment, (3) energy, (4) protein, (5) supplementation, and (6) percutaneous endoscopic gastrostomy (PEG). This review summarizes relevant and updated nutritional recommendations to maintain or restore the nutritional status of patients with ALS, contributing to their quality of life and survival time. Conclusions: These nutritional recommendations will help health professionals and caregivers to implement and standardize nutritional care according to evidence-based practice in ALS. PROSPERO registration number CRD42021233088.}, } @article {pmid40076771, year = {2025}, author = {Aguiar, B and Alfenim, AR and Machado, CS and Moreira, J and Pinto, M and Otero-Espinar, FJ and Borges, F and Fernandes, C}, title = {Exploring Nano-Delivery Systems to Enhance the Edaravone Performance in Amyotrophic Lateral Sclerosis Treatment.}, journal = {International journal of molecular sciences}, volume = {26}, number = {5}, pages = {}, pmid = {40076771}, issn = {1422-0067}, support = {2023.13291.PEX//Foundation for Science and tecnhology/ ; UIDB/00081/2020 (CIQUP)//Foundation for Science and Technology/ ; LA/P/0056/2020(IMS)//Foundation for Science and Technology/ ; 2021.04016.CEECIND/CP1655/CT0004//Foundation for Science and Technology/ ; IMPULSE: IMproving User experience, Long-term sustainability, and Services//EU-OPENSCREEN HORIZON-INFRA-2023-DEV-0/ ; 2020.08731.BD//Foundation for Science and Technology/ ; 2023.01250.BD//Foundation for Science and Technology/ ; 2024.00809.BD//Foundation for Science and Technology/ ; SFRH/BD/145637/2019//Foundation for Science and Technology/ ; }, mesh = {*Edaravone/chemistry/pharmacology/administration & dosage ; *Amyotrophic Lateral Sclerosis/drug therapy ; Humans ; *Nanoparticles/chemistry ; *Drug Delivery Systems/methods ; Polyethylene Glycols/chemistry ; Drug Carriers/chemistry ; Cell Line, Tumor ; }, abstract = {Edaravone is one of the treatment options for Amyotrophic Lateral Sclerosis, but its therapeutic efficacy is limited due to the incapacity to cross the blood-brain barrier, as well as its short life span and poor stability, which is ultimately caused by its tautomerism in physiological condions. This work presents an overview about the use of several nanoformulations based on polymeric, protein, lipidic, or hybrid structure as suitable and stable drug delivery systems for encapsulating edaravone. We also evaluated the functionalization of nanoparticles with pegylated chains using the polyethylene glycol or tocopherol polyethylene glycol succinate and the possibility of preparing polymeric nanoparticles at different pH (7.4, 9, and 11). Edaravone was sucessfully encapsulated in polymeric, lipid-polymer hybrid, and lipidic nanoparticles. The use of higher pH values in the synthesis of polymeric nanoparticles has led to a decrease in nanoparticle size and an increase in the percentage of encapsulation efficiency. However, the resulting nanoformulations are not stable. Only polymeric and hybrid nanoparticles showed good stability over 80 days of storage, mainly at 4 °C. Overall, the nanoformulations tested did not show cytotoxicity in the SH-SY5Y cell line except the nanostructured lipid carrier formulations that showed some cytotoxicity possibly due to lipidic peroxidation. In conclusion, this work shows that edaravone can be encapsulated in different nanocarriers that could act as an interesting alternative for the treatment of Amyotrophic Lateral Sclerosis.}, } @article {pmid40075757, year = {2025}, author = {Rizzo, GEM and Coluccio, C and Forti, E and Fugazza, A and Binda, C and Vanella, G and Di Matteo, FM and Crinò, SF and Lisotti, A and Maida, MF and Aragona, G and Mauro, A and Repici, A and Anderloni, A and Fabbri, C and Tarantino, I and On Behalf Of The I-Eus Group, }, title = {Endoscopic Ultrasound-Guided Anastomoses of the Gastrointestinal Tract: A Multicentric Experience.}, journal = {Cancers}, volume = {17}, number = {5}, pages = {}, pmid = {40075757}, issn = {2072-6694}, support = {N/A//I-EUS working group/ ; }, abstract = {This multicenter retrospective study included patients undergoing EUS-guided GI anastomoses from 2016 to 2023. Indications for EUS-guided anastomosis were GOO, ALS or patients with altered anatomy needing endoscopic interventions. The primary outcome was technical success, while secondary outcomes included clinical success, safety, lumen-apposing metal stent (LAMS) patency, and the need for reinterventions. A total of 216 patients (mean age 64.5 [±13.94] years; 49.1% males) were included. In total, 149 cases (69%) were GOO, 44 (20.4%) cases were bilioenteric anastomotic strictures or lithiasis in altered anatomy, 14 cases (6.5%) were ALS, and 9 patients (4.2%) were for ERCP in altered anatomy after EUS-GG. Overall, EUS-GE was performed in 181 patients (83.8%), EUS-JJ in 44 cases (20.4%), and EUS-GG in 10 (4.6%). Technical success was 94.91%, and clinical success was 93.66%. The adverse event (AE) rate was 11.1%. The reintervention rate was 7.69%. The median follow-up was 85 days. In conclusions, EUS-guided GI anastomoses are technically feasible and safe in both malignant and benign diseases.}, } @article {pmid40075315, year = {2025}, author = {Soliman, R and Fahmy, N and Swelam, MS}, title = {Headache types and characteristics in patients with Amyotrophic Lateral Sclerosis.}, journal = {The journal of headache and pain}, volume = {26}, number = {1}, pages = {53}, pmid = {40075315}, issn = {1129-2377}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/complications/epidemiology/physiopathology ; Male ; Female ; Middle Aged ; Cross-Sectional Studies ; Adult ; Aged ; *Migraine Disorders/etiology/epidemiology/physiopathology ; *Tension-Type Headache/etiology/epidemiology/physiopathology ; *Headache Disorders, Primary/etiology/physiopathology/epidemiology ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder associated with progressive loss of motor neurons, this result in muscle denervation, atrophy and consequently death takes place due to respiratory failure within 3-5 years of onset of symptoms.

OUR AIM: Was to investigate types and frequency of headache in ALS patients.

METHODS: This is cross sectional hospital based study. Clinically definite 100 ALS Patients (diagnosed according to El Escorial revised criteria) were recruited out of 137 ALS patients presented to the Neuromuscular Clinic in Ain Shams university Hospital from February 2022 to June 2024. Patients were screened for headache types and symptoms diagnosed according to International Headache Society criteria (IHS). Headache severity and impact were assessed using Arabic versions of Headache Impact Test (HIT) and Migraine Disability Assessment (MIDAS). Depression was also assessed via Arabic version of Beck's Depression Inventory (BDI). ALS symptoms severity was assessed via Arabic version of Amyotrophic Lateral Sclerosis Functional Rating Scale Revised (ALSFRS-R). Cognitive functions were assessed via the Egyptian version of the Edinburgh Cognitive and Behavioral Amyotrophic Lateral Sclerosis Screen (ECAS‑EG). Demographic data and ALS related parameters were collected.

RESULTS: Among 100 patients with clinically definite ALS, 79 patients reported headaches, 62 of them had primary headaches; with tension-type headache being the most commonly reported in 46 patients, Migraine in 16 patients. Fifteen ALS patients had secondary headaches; among them 12 had headache secondary to respiratory insufficiency and 3 patients developed headache after the initiation of Riluzole therapy. Two patients had non specific headache. Mean age for the patients at ALS presentation was 43.9 ± 13.8, Mean ALSFRS-R score 33.3 ± 9.04. The relationships between headache and clinical features of ALS were also investigated.

IN CONCLUSION: ALS patients should be evaluated for Headache; Not only headache secondary to respiratory compromise and hypercapnea, but also primary headaches which can be overlooked in patients with ALS.}, } @article {pmid40075110, year = {2025}, author = {Raas, Q and Haouy, G and de Calbiac, H and Pasho, E and Marian, A and Guerrera, IC and Rosello, M and Oeckl, P and Del Bene, F and Catanese, A and Ciura, S and Kabashi, E}, title = {TBK1 is involved in programmed cell death and ALS-related pathways in novel zebrafish models.}, journal = {Cell death discovery}, volume = {11}, number = {1}, pages = {98}, pmid = {40075110}, issn = {2058-7716}, support = {682622//EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council)/ ; }, abstract = {Pathogenic mutations within the TBK1 gene leading to haploinsufficiency are causative of amyotrophic lateral sclerosis (ALS). This gene is linked to autophagy and inflammation, two cellular mechanisms reported to be dysregulated in ALS patients, although its functional role in the pathogenesis could involve other players. We targeted the TBK1 ortholog in zebrafish, an optimal vertebrate model for investigating genetic defects in neurological disorders. We generated zebrafish models with invalidating tbk1 mutations using CRISPR-Cas9 or tbk1 knockdown models using antisense morpholino oligonucleotide (AMO). The early motor phenotype of zebrafish injected with tbk1 AMO beginning at 2 days post fertilization (dpf) is associated with the degeneration of motor neurons. In parallel, CRISPR-induced tbk1 mutants exhibit impaired motor function beginning at 5 dpf and increased lethality beginning at 9 dpf. A metabolomic analysis showed an association between tbk1 loss and severe dysregulation of nicotinamide metabolism, and incubation with nicotinamide riboside rescued the motor behavior of tbk1 mutant zebrafish. Furthermore, a proteomic analysis revealed increased levels of inflammatory markers and dysregulation of programmed cell death pathways. Necroptosis appeared to be strongly activated in TBK1 fish, and larvae treated with the necroptosis inhibitor necrosulfonamide exhibited improved survival. Finally, a combined analysis of mutant zebrafish and TBK1-mutant human motor neurons revealed dysregulation of the KEGG pathway "ALS", with disrupted nuclear-cytoplasmic transport and increased expression of STAT1. These findings point toward a major role for necroptosis in the degenerative features and premature lethality observed in tbk1 mutant zebrafish. Overall, the novel tbk1-deficient zebrafish models offer a great opportunity to better understand the cascade of events leading from the loss of tbk1 expression to the onset of motor deficits, with involvement of a metabolic defect and increased cell death, and for the development of novel therapeutic avenues for ALS and related neuromuscular diseases.}, } @article {pmid40074931, year = {2025}, author = {Michielsen, A and van Veenhuijzen, K and Hiemstra, F and Jansen, IM and Kalkhoven, B and Veldink, JH and Kruitwagen, ET and van Es, M and van Zandvoort, MJE and van den Berg, LH and Westeneng, HJ}, title = {Cognitive impairment within and beyond the FTD spectrum in ALS: development of a complementary cognitive screen.}, journal = {Journal of neurology}, volume = {272}, number = {4}, pages = {268}, pmid = {40074931}, issn = {1432-1459}, support = {grant agreement no 772376- EScORIAL//H2020 European Research Council/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/complications/psychology/diagnosis ; Male ; Female ; *Frontotemporal Dementia/diagnosis/complications/psychology ; Middle Aged ; *Cognitive Dysfunction/diagnosis/etiology ; Aged ; *Neuropsychological Tests ; Adult ; }, abstract = {OBJECTIVE: To investigate cognitive impairments in amyotrophic lateral sclerosis (ALS), extending both within and beyond the established frontotemporal dementia (FTD) spectrum, using the Complementary Cognitive ALS Screen (C-CAS).

METHODS: The C-CAS, designed to complement the Edinburgh cognitive and behavioural ALS screen (ECAS), explores cognitive (sub)domains not investigated by the ECAS. Normative data were collected, and models adjusted for age, sex, and education level were developed. Item scores below the 5th percentile in controls were considered abnormal. A sum score was constructed, and C-CAS impairments were compared between ALS patients and controls, and to ECAS impairments.

RESULTS: Data from 314 controls and 184 ALS patients were analyzed. The C-CAS is feasible, well-tolerated, and takes 15-20 min to complete. ALS patients performed worse across all 12 items. Within the FTD spectrum, impairments in social cognition, inhibition, and cognitive flexibility were identified in up to 16%, 14%, and 12% of ALS patients, respectively, with minimal overlap with ECAS impairments. Beyond the FTD spectrum, impairments were found in visuoconstruction, incidental non-verbal memory and body orientation (13% each), with minimal overlap with ECAS memory or visuospatial impairments. Overall, 24% of the ALS patients obtained an abnormal C-CAS sum score. Compared to the ECAS, the C-CAS detected additional impairments in 15% of ALS patients. Item-specific and sum score results based on normative data can be accessed at (https://apps4mnd.com/ccas/).

INTERPRETATION: We identified cognitive impairments in ALS within and beyond the FTD spectrum not captured by existing screening tools. The C-CAS complements the ECAS, improving personalized counseling and research stratification in ALS.}, } @article {pmid40074537, year = {2025}, author = {Mkhize, L and Marimani, M and Duze, ST}, title = {Characterization of Vibrio cholerae from the Jukskei River in Johannesburg, South Africa.}, journal = {Letters in applied microbiology}, volume = {78}, number = {3}, pages = {}, doi = {10.1093/lambio/ovaf036}, pmid = {40074537}, issn = {1472-765X}, support = {138279//National Research Foundation/ ; RKSST23//Carnegie DTA/ ; }, mesh = {South Africa ; *Rivers/microbiology ; *Vibrio cholerae/genetics/isolation & purification/classification/drug effects/pathogenicity ; Virulence Factors/genetics ; Bacterial Proteins/genetics ; Cholera/microbiology ; Drug Resistance, Bacterial/genetics ; }, abstract = {The current study aimed to isolate and characterize Vibrio cholerae isolated from the Jukskei River, one of the largest Rivers in Johannesburg, South Africa. Water samples collected from the Jukskei River were subjected to culture-based methods for the detection and isolation of V. cholerae. Twenty-four V. cholerae were isolated, confirmed using real-time PCR, and sequenced using the MInION portable nanopore-sequencing device. Reference-based genome assemblies were constructed from the raw reads using the EPI2ME software followed by bioinformatics analysis using the Centre for Genomic Epidemiology website. All the V. cholerae isolates isolated from the Jukskei River were classified as non-O1/non-O139 and none of the isolates harbored the cholera toxin gene, ctxA. All 24 V. cholerae isolates belonged to sequence type 741, virulent genes including toxR, vspD, als, hlyA, makA, and rtxA as well as the Vibrio pathogenicity island 2 were detected amongst the isolates. Antimicrobial resistance genes (parC, varG, and gyrA) were detected in 83% of isolates. Although V. cholerae non-O1/non-O139 are not associated with epidemic cholera they can still cause mild to life-threatening illnesses. Therefore, increased surveillance should be considered to better understand the public health risks to the local community.}, } @article {pmid40074390, year = {2025}, author = {Cappa, SF}, title = {Hemispheric asymmetry in neurodegenerative diseases.}, journal = {Handbook of clinical neurology}, volume = {208}, number = {}, pages = {101-112}, doi = {10.1016/B978-0-443-15646-5.00009-9}, pmid = {40074390}, issn = {0072-9752}, mesh = {Humans ; *Neurodegenerative Diseases/pathology/physiopathology ; *Functional Laterality/physiology ; *Brain/pathology ; }, abstract = {Hemispheric asymmetry in pathologic involvement is frequently observed in neurodegenerative disorders (NDD) and is responsible for differences in cognitive and motor clinical manifestations in individual patients. While asymmetry is modest in typical Alzheimer disease (AD), atypical AD presentations with prominent language impairment [logopenic/phonologic variant of primary progressive aphasia (L/Phv-PPA)] are associated with prevalent involvement of the language-dominant hemisphere. Similarly, in the frontotemporal dementia-amyotrophic lateral sclerosis (FTD-ALS) spectrum, the semantic (Sv) and nonfluent/agrammatic (Nf/Av) variants of PPA are due to asymmetric pathology involving the language-dominant hemisphere. A reversed (typically right-sided) pattern of asymmetry is often found in conditions associated with prominent disorders of behavior and social cognition (i.e., behavioral variant of frontotemporal degeneration-Bv FTD). Asymmetry is generally modest and less consistent in NDD with prevalent motor manifestations, such as Parkinson disease (PD). Overall, the pattern of hemispheric involvement reflects the network-specific selectivity of NDD and is compatible with the spreading of pathology along connection pathways.}, } @article {pmid40073860, year = {2025}, author = {Zhang, Z and Fu, X and Wright, N and Wang, W and Ye, Y and Asbury, J and Li, Y and Zhu, C and Wu, R and Wang, S and Sun, S}, title = {PTPσ-mediated PI3P regulation modulates neurodegeneration in C9ORF72-ALS/FTD.}, journal = {Neuron}, volume = {113}, number = {8}, pages = {1190-1205.e9}, pmid = {40073860}, issn = {1097-4199}, support = {R01 AG078948/AG/NIA NIH HHS/United States ; R21 AG072078/AG/NIA NIH HHS/United States ; RF1 NS113820/NS/NINDS NIH HHS/United States ; RF1 NS127925/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; *C9orf72 Protein/genetics/metabolism ; Humans ; *Frontotemporal Dementia/genetics/metabolism/pathology ; *Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology ; Mice ; Neurons/metabolism/pathology ; Lysosomes/metabolism ; *Receptor-Like Protein Tyrosine Phosphatases, Class 2/metabolism/genetics/antagonists & inhibitors ; *Phosphatidylinositol Phosphates/metabolism ; Endosomes/metabolism ; }, abstract = {The most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) is the repeat expansion in C9ORF72. Dipeptide repeat (DPR) proteins translated from both sense and antisense repeats, especially arginine-rich DPRs (R-DPRs), contribute to neurodegeneration. Through CRISPR interference (CRISPRi) screening in human-derived neurons, we identified receptor-type tyrosine-protein phosphatase S (PTPσ) as a strong modifier of poly-GR-mediated toxicity. We showed that reducing PTPσ promotes the survival of both poly-GR- and poly-PR-expressing neurons by elevating phosphatidylinositol 3-phosphate (PI3P), accompanied by restored early endosomes and lysosomes. Remarkably, PTPσ knockdown or inhibition substantially rescues the PI3P-endolysosomal defects and improves the survival of C9ORF72-ALS/FTD patient-derived neurons. Furthermore, the PTPσ inhibitor diminishes GR toxicity and rescues pathological and behavioral phenotypes in mice. Overall, these findings emphasize the critical role of PI3P-mediated endolysosomal deficits induced by R-DPRs in disease pathogenesis and reveal the therapeutic potential of targeting PTPσ in C9ORF72-ALS/FTD.}, } @article {pmid40073394, year = {2025}, author = {Janes, WE and Marchal, N and Song, X and Popescu, M and Mosa, ASM and Earwood, JH and Jones, V and Skubic, M}, title = {Integrating Ambient In-Home Sensor Data and Electronic Health Record Data for the Prediction of Outcomes in Amyotrophic Lateral Sclerosis: Protocol for an Exploratory Feasibility Study.}, journal = {JMIR research protocols}, volume = {14}, number = {}, pages = {e60437}, pmid = {40073394}, issn = {1929-0748}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology/diagnosis ; *Electronic Health Records ; Feasibility Studies ; Machine Learning ; Algorithms ; *Monitoring, Ambulatory/methods/instrumentation ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) leads to rapid physiological and functional decline before causing untimely death. Current best-practice approaches to interdisciplinary care are unable to provide adequate monitoring of patients' health. Passive in-home sensor systems enable 24×7 health monitoring. Combining sensor data with outcomes extracted from the electronic health record (EHR) through a supervised machine learning algorithm may enable health care providers to predict and ultimately slow decline among people living with ALS.

OBJECTIVE: This study aims to describe a federated approach to assimilating sensor and EHR data in a machine learning algorithm to predict decline among people living with ALS.

METHODS: Sensor systems have been continuously deployed in the homes of 4 participants for up to 330 days. Sensors include bed, gait, and motion sensors. Sensor data are subjected to a multidimensional streaming clustering algorithm to detect changes in health status. Specific health outcomes are identified in the EHR and extracted via the REDCap (Research Electronic Data Capture; Vanderbilt University) Fast Healthcare Interoperability Resource directly into a secure database.

RESULTS: As of this writing (fall 2024), machine learning algorithms are currently in development to predict those health outcomes from sensor-detected changes in health status. This methodology paper presents preliminary results from one participant as a proof of concept. The participant experienced several notable changes in activity, fluctuations in heart rate and respiration rate, and reductions in gait speed. Data collection will continue through 2025 with a growing sample.

CONCLUSIONS: The system described in this paper enables tracking the health status of people living with ALS at unprecedented levels of granularity. Combined with tightly integrated EHR data, we anticipate building predictive models that can identify opportunities for health care services before adverse events occur. We anticipate that this system will improve and extend the lives of people living with ALS.

DERR1-10.2196/60437.}, } @article {pmid40072375, year = {2025}, author = {Gong, Z and Ba, L and Li, Z and Hou, H and Zhang, M}, title = {CD16[-]CD56[bright] NK Cells: A Protective NK Cell Subset for Progression and Prognosis in Amyotrophic Lateral Sclerosis.}, journal = {Aging and disease}, volume = {}, number = {}, pages = {}, doi = {10.14336/AD.2024.1597}, pmid = {40072375}, issn = {2152-5250}, abstract = {Amyotrophic lateral sclerosis (ALS) is a non-neuron-autonomous disease where peripheral immune dysregulation significantly impacts disease progression. However, the immunopathological mechanisms of natural killer (NK) cells in ALS remain largely unexplored. This study enrolled 241 ALS patients and 102 healthy controls (HC), analyzing lymphocyte subsets, including T cells, B cells, and NK cells. A sub-cohort of 81 ALS patients was followed up for one year at three-month intervals. Linear mixed and Cox proportional hazards models were used to evaluate the association between lymphocyte subsets and ALS progression and prognosis. Our results revealed significant reductions in total T cells, helper T cells (Th), and NK cells in ALS patients compared to HC (P &;lt 0.05). Slow-progressing ALS patients exhibited higher counts of total T cells, Th, CD16-CD56[bright] NK cells, and CD16[+]CD56[bright] NK cells, while showing lower counts of CD16[+]CD56[dim] NK cells compared to fast-progressing ALS patients (P &;lt 0.05). ALS patients with lower CD16[-]CD56[bright] NK cell counts experienced a faster decline in motor function than those with higher counts (P &;lt 0.05). Elevated CD16[-]CD56[bright] NK cell counts were associated with improved ALS prognosis (HR, 0.73; 95% CI: 0.60-0.90; P &;lt 0.05). This study suggests that CD16[-]CD56[bright] NK cells play a protective role in ALS progression and prognosis, offering a potential therapeutic target for ALS.}, } @article {pmid40072076, year = {2025}, author = {Calvo, B and Schembri-Wismayer, P and Durán-Alonso, MB}, title = {Age-Related Neurodegenerative Diseases: A Stem Cell's Perspective.}, journal = {Cells}, volume = {14}, number = {5}, pages = {}, pmid = {40072076}, issn = {2073-4409}, mesh = {Humans ; *Neurodegenerative Diseases/pathology/therapy ; *Aging/pathology ; *Stem Cells/metabolism ; Animals ; }, abstract = {Neurodegenerative diseases encompass a number of very heterogeneous disorders, primarily characterized by neuronal loss and a concomitant decline in neurological function. Examples of this type of clinical condition are Alzheimer's Disease, Parkinson's Disease, Huntington's Disease and Amyotrophic Lateral Sclerosis. Age has been identified as a major risk in the etiology of these disorders, which explains their increased incidence in developed countries. Unfortunately, despite continued and intensive efforts, no cure has yet been found for any of these diseases; reliable markers that allow for an early diagnosis of the disease and the identification of key molecular events leading to disease onset and progression are lacking. Altered adult neurogenesis appears to precede the appearance of severe symptoms. Given the scarcity of human samples and the considerable differences with model species, increasingly complex human stem-cell-based models are being developed. These are shedding light on the molecular alterations that contribute to disease development, facilitating the identification of new clinical targets and providing a screening platform for the testing of candidate drugs. Moreover, the secretome and other promising features of these cell types are being explored, to use them as replacement cells of high plasticity or as co-adjuvant therapy in combinatorial treatments.}, } @article {pmid40070688, year = {2025}, author = {Hosseini Faradonbeh, SM and Seyedalipour, B and Keivan Behjou, N and Rezaei, K and Baziyar, P and Hosseinkhani, S}, title = {Structural insights into SOD1: from in silico and molecular dynamics to experimental analyses of ALS-associated E49K and R115G mutants.}, journal = {Frontiers in molecular biosciences}, volume = {12}, number = {}, pages = {1532375}, pmid = {40070688}, issn = {2296-889X}, abstract = {Protein stability is a crucial characteristic that influences both protein activity and structure and plays a significant role in several diseases. Cu/Zn superoxide dismutase 1 (SOD1) mutations serve as a model for elucidating the destabilizing effects on protein folding and misfolding linked to the lethal neurological disease, amyotrophic lateral sclerosis (ALS). In the present study, we have examined the structure and dynamics of the SOD1 protein upon two ALS-associated point mutations at the surface (namely, E49K and R115G), which are located in metal-binding loop IV and Greek key loop VI, respectively. Our analysis was performed through multiple algorithms on the structural characterization of the hSOD1 protein using computational predictions, molecular dynamics (MD) simulations, and experimental studies to understand the effects of amino acid substitutions. Predictive results of computational analysis predicted the deleterious and destabilizing effect of mutants on hSOD1 function and stability. MD outcomes also indicate that the mutations result in structural destabilization by affecting the increased content of β-sheet structures and loss of hydrogen bonds. Moreover, comparative intrinsic and extrinsic fluorescence results of WT-hSOD1 and mutants indicated structural alterations and increased hydrophobic surface pockets, respectively. As well, the existence of β-sheet-dominated structures was observed under amyloidogenic conditions using FTIR spectroscopy. Overall, our findings suggest that mutations in the metal-binding loop IV and Greek key loop VI lead to significant structural and conformational changes that could affect the structure and stability of the hSOD1 molecule, resulting in the formation of toxic intermediate species that cause ALS.}, } @article {pmid40069959, year = {2025}, author = {Chiò, A and Foucher, J and Gwathmey, KG and Ingre, C}, title = {Minimum clinically important difference for drug effectiveness in an area of patient-oriented therapeutic goals in amyotrophic lateral sclerosis.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {26}, number = {5-6}, pages = {389-398}, doi = {10.1080/21678421.2025.2475893}, pmid = {40069959}, issn = {2167-9223}, mesh = {*Amyotrophic Lateral Sclerosis/drug therapy/diagnosis ; Humans ; *Minimal Clinically Important Difference ; Randomized Controlled Trials as Topic ; Treatment Outcome ; Quality of Life ; }, abstract = {Objective: In this review, we will examine the more common endpoints incorporated in randomized controlled trials (RCTs) and their strength of evidence, focusing on the definition of what constitutes a clinically meaningful change. We will also reflect on the perspective of patients and their families regarding the design of RCTs in amyotrophic lateral sclerosis (ALS). Methods: Authors performed a scoping review of the literature around clinical meaningfulness in the ALS field and the minimum clinically important difference to deem a treatment effective. Results: The use of survival as an RCT endpoint, as well as the ALS functional rating scale-revised slope, has been criticized, and their relevance for patients remains debated. Biomarkers are promising alternatives as surrogate endpoints, but currently, only cerebrospinal fluid and plasma neurofilaments have emerged as reliable and sensitive biomarkers of disease progression. Incorporating patients' preferences and priorities for their care when treatments are selected is important to minimize the burden of care and limit the potential harms of overtreatment. Patients' interest in and acceptance of a new therapy is also determined by its impact on their quality of life. Discussion and conclusion: While scientifically sound trials must be conducted, this must be balanced with patient expectations of limiting trial burden, duration and placebo usage. An important approach in uniting these diverging needs is the inclusion of people with ALS and their organizations to advise in the design and execution of clinical trials, facilitating the design of RCTs more focused on patients' expectations while retaining a high scientific rigor.}, } @article {pmid40069809, year = {2025}, author = {Jonsdottir, G and Vilhjalmsson, R and Sigurdardottir, V and Hjaltason, H and Klinke, ME and Jonsdottir, H}, title = {Nursing contribution to end-of-life care decision-making in patients with neurological diseases on an acute hospital ward: documentation of signs and symptoms.}, journal = {BMC nursing}, volume = {24}, number = {1}, pages = {271}, pmid = {40069809}, issn = {1472-6955}, support = {71545//Icelandic Nurses Association/ ; }, abstract = {BACKGROUND: Recognizing impending death in patients with neurological diseases presents challenges for nurses and other healthcare professionals. This study aimed to identify nursing contribution to end-of-life (EOL) care decision-making for patients with neurological diseases in an acute hospital ward and to compare signs and symptoms among subgroups of patients.

METHODS: In this retrospective study, we analyzed data from 209 patient health records using the Neurological End-Of-Life Care Assessment Tool to evaluate the care in the last 3 to 7 days of life. Key aspects included the need for EOL care, EOL care decision-making, signs and symptoms of imminent death, and communication with relatives. The patient records pertain to patients who died in an acute neurological ward between January 2011 and August 2020; 123 with ischemic stroke, 48 with hemorrhagic stroke, 27 with amyotrophic lateral sclerosis [ALS], and 11 with Parkinson's disease or extrapyramidal and movement disorders [PDoed]. Both descriptive and inferential statistical analyses were performed to analyze the data.

RESULTS: Nurses identified the need for EOL care in 36% of cases and contributed to EOL decision-making as information brokers (15%), advocates (6%), and supporters (6%). They identified disease progression in 44% of the cases. The mean number of signs and symptoms in both the acute and progressive disease groups was 6.5 and ranged from 1 to 14. Patients with stroke without a documented EOL decision had more severe symptoms, including respiratory congestion (68%) and dyspnea (37%), than those with EOL decision. A higher frequency of no food intake was documented in patients with stroke receiving EOL care (p = 0.007) compared to those without. Among patients with ALS or PDoed, those with EOL decision showed a trend toward a higher frequency of unconsciousness or limited consciousness than those without EOL decision (p = 0.067). For all groups of patients, conversations with relatives occurred in 85% instances and family meetings in 93%.

CONCLUSIONS: Nurses made substantial contributions to EOL care decision-making for patients with neurological diseases. To improve early identification of imminent death in patients with neurological diseases in acute hospital wards, healthcare professionals must investigate barriers contributing to delayed recognition.

CLINICAL TRIAL NUMBER: Not applicable.}, } @article {pmid40069360, year = {2025}, author = {Cheng, M and Lu, D and Li, K and Wang, Y and Tong, X and Qi, X and Yan, C and Ji, K and Wang, J and Wang, W and Lv, H and Zhang, X and Kong, W and Zhang, J and Ma, J and Li, K and Wang, Y and Feng, J and Wei, P and Li, Q and Shen, C and Fu, XD and Ma, Y and Zhang, X}, title = {Mitochondrial respiratory complex IV deficiency recapitulates amyotrophic lateral sclerosis.}, journal = {Nature neuroscience}, volume = {28}, number = {4}, pages = {748-756}, pmid = {40069360}, issn = {1546-1726}, support = {2019YFA0508701//Ministry of Science and Technology of the People's Republic of China (Chinese Ministry of Science and Technology)/ ; 2022YFA1303300//Ministry of Science and Technology of the People's Republic of China (Chinese Ministry of Science and Technology)/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/genetics/pathology/metabolism ; Animals ; Rats ; Motor Neurons/metabolism/pathology ; *Electron Transport Complex IV/genetics ; *Mitochondria/metabolism/genetics ; Humans ; Disease Models, Animal ; Mutation/genetics ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is categorized into ~10% familial and ~90% sporadic cases. While familial ALS is caused by mutations in many genes of diverse functions, the underlying pathogenic mechanisms of ALS, especially in sporadic ALS (sALS), are largely unknown. Notably, about half of the cases with sALS showed defects in mitochondrial respiratory complex IV (CIV). To determine the causal role of this defect in ALS, we used transcription activator-like effector-based mitochondrial genome editing to introduce mutations in CIV subunits in rat neurons. Our results demonstrate that neuronal CIV deficiency is sufficient to cause a number of ALS-like phenotypes, including cytosolic TAR DNA-binding protein 43 redistribution, selective motor neuron loss and paralysis. These results highlight CIV deficiency as a potential cause of sALS and shed light on the specific vulnerability of motor neurons, marking an important advance in understanding and therapeutic development of sALS.}, } @article {pmid40067829, year = {2025}, author = {O'Neill, K and Shaw, R and Bolger, I and , and Tam, OH and Phatnani, H and Gale Hammell, M}, title = {ALS molecular subtypes are a combination of cellular and pathological features learned by deep multiomics classifiers.}, journal = {Cell reports}, volume = {44}, number = {3}, pages = {115402}, pmid = {40067829}, issn = {2211-1247}, support = {R01 NS116350/NS/NINDS NIH HHS/United States ; T32 GM065094/GM/NIGMS NIH HHS/United States ; RF1 NS118570/NS/NINDS NIH HHS/United States ; R01 NS118570/NS/NINDS NIH HHS/United States ; P30 CA045508/CA/NCI NIH HHS/United States ; R01 NS118183/NS/NINDS NIH HHS/United States ; }, mesh = {*Amyotrophic Lateral Sclerosis/genetics/pathology/classification ; Humans ; Transcriptome/genetics ; Neuroglia/metabolism/pathology ; Spinal Cord/pathology/metabolism ; Neurons/metabolism/pathology ; Male ; *Genomics/methods ; Female ; Microglia/metabolism/pathology ; Multiomics ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a complex syndrome with multiple genetic causes and wide variation in disease presentation. Despite this heterogeneity, large-scale genomics studies revealed that ALS postmortem samples can be grouped into a small number of subtypes, defined by transcriptomic signatures of mitochondrial dysfunction and oxidative stress (ALS-Ox), microglial activation and neuroinflammation (ALS-Glia), or TDP-43 pathology and associated transposable elements (ALS-TE). In this study, we present a deep ALS neural net classifier (DANCer) for ALS molecular subtypes. Applying DANCer to an expanded cohort from the NYGC ALS Consortium highlights two subtypes that strongly correlate with disease duration: ALS-TE in cortex and ALS-Glia in spinal cord. Finally, single-nucleus transcriptomes demonstrate that ALS subtypes are recapitulated in neurons and glia, with both ALS-wide and subtype-specific alterations in all cell types. In summary, ALS molecular subtypes represent a combination of cellular and pathological features that correlate with clinical features of ALS.}, } @article {pmid40067821, year = {2025}, author = {, and Berry, JD and Maragakis, NJ and Macklin, EA and Chibnik, LB and Quintana, M and Saville, BR and Detry, MA and Vestrucci, M and Marion, J and McGlothlin, A and Stommel, EW and Chase, M and Pothier, L and Harkey, BA and Yu, H and Sherman, A and Shefner, J and Hall, M and Kittle, G and Babu, S and Andrews, J and D'Agostino, D and Tustison, E and Scirocco, E and Giacomelli, E and Alameda, G and Locatelli, E and Ho, D and Quick, A and Ajroud-Driss, S and Katz, J and Heitzman, D and Appel, SH and Shroff, S and Felice, KJ and Simmons, Z and Miller, T and Olney, N and Weiss, MD and Goutman, SA and Fernandes, JA and Jawdat, O and Owegi, MA and Foster, L and Vu, T and Ilieva, H and Newman, DS and Arcila-Londono, X and Jackson, C and Ladha, S and Heiman-Patterson, T and Caress, J and Swenson, A and Peltier, A and Lewis, R and Fee, D and Elliott, M and Bedlack, R and Kasarskis, EJ and Elman, L and Rosenfeld, J and Walk, D and McIlduff, CE and Twydell, P and Young, E and Johnson, K and Rezania, K and Goyal, NA and Cohen, JA and Benatar, M and Jones, V and Glass, J and Shah, J and Beydoun, SR and Wymer, JP and Zilliox, L and Nayar, S and Pattee, GL and Martinez-Thompson, J and Rynders, A and Evan, J and Evan, J and Hartford, A and Sepassi, M and Ho, KS and Glanzman, R and Greenberg, B and Hotchkin, MT and Paganoni, S and Cudkowicz, ME and , }, title = {CNM-Au8 in Amyotrophic Lateral Sclerosis: The HEALEY ALS Platform Trial.}, journal = {JAMA}, volume = {333}, number = {13}, pages = {1138-1149}, pmid = {40067821}, issn = {1538-3598}, abstract = {IMPORTANCE: Bioenergetic failure has been proposed as a driver of amyotrophic lateral sclerosis (ALS). CNM-Au8 is a suspension of gold nanocrystals that catalyzes the conversion of nicotinamide adenine dinucleotide hydride into NAD+, resulting in an increase of cellular adenosine triphosphate production.

OBJECTIVE: To determine the effects of CNM-Au8 on ALS disease progression.

CNM-Au8 was tested as a regimen of the HEALEY ALS Platform Trial, a phase 2/3, multicenter, randomized, double-blind platform trial. The study was conducted at 54 sites in the US from July 2020 to March 2022 (final follow-up, March 17, 2022). A total of 161 participants with ALS were randomized to receive CNM-Au8 (n = 120) or regimen-specific placebo (n = 41). Data from 123 concurrently randomized placebo participants in other regimens were combined for analyses.

INTERVENTIONS: Eligible participants were randomized in a 3:3:2 ratio to receive CNM-Au8 60 mg daily (n = 61), CNM-Au8 30 mg daily (n = 59), or matching placebo (n = 41) for 24 weeks.

MAIN OUTCOMES AND MEASURES: The primary efficacy outcome was change from baseline through week 24 in ALS disease severity measured by a bayesian shared parameter model of function (based on the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale) and survival, which provided an estimate of the rate of disease progression measured by the disease rate ratio (DRR), with a DRR of less than 1 indicating treatment benefit. Secondary end points included a Combined Assessment of Function and Survival using a joint-rank test, rate of decline in slow vital capacity (percent predicted), and survival free of permanent assisted ventilation.

RESULTS: Among 161 participants who were randomized within the CNM-Au8 regimen (mean age, 58.4 years; 61 [37.9%] female), 145 (90%) completed the trial. In the primary analysis comparing the combined CNM-Au8 dosage groups vs the combined placebo groups, the primary end point (DRR, 0.97 [95% credible interval, 0.783-1.175]; posterior probability of DRR <1, 0.65) and the 3 secondary end points suggested no benefit or harm of CNM-Au8. In the active (n = 120) vs placebo (n = 163) groups, the most common adverse events were diarrhea (23 [19%] vs 12 [7%]), nausea (17 [14.2%] vs 14 [8.6%]), fatigue (12 [10.8%] vs 30 [18.4%]), and muscular weakness (24 [20%] vs 45 [27.6%]).

CONCLUSIONS AND RELEVANCE: No benefit of CNM-Au8 on ALS disease progression was observed at 24 weeks.

TRIAL REGISTRATION: ClinicalTrials.gov Identifiers: NCT04297683, NCT04414345.}, } @article {pmid40067755, year = {2025}, author = {, and Shefner, JM and Oskarsson, B and Macklin, EA and Chibnik, LB and Quintana, M and Saville, BR and Detry, MA and Vestrucci, M and Marion, J and McGlothlin, A and Heiman-Patterson, T and Chase, M and Pothier, L and Harkey, BA and Yu, H and Sherman, AV and Hall, M and Kittle, G and Berry, JD and Babu, S and Andrews, J and D'Agostino, D and Tustison, E and Scirocco, E and Giacomelli, E and Alameda, G and Locatelli, E and Ho, D and Quick, A and Ajroud-Driss, S and Katz, J and Heitzman, D and Appel, SH and Shroff, S and Felice, K and Maragakis, NJ and Simmons, Z and Miller, TM and Olney, N and Weiss, MD and Goutman, SA and Fernandes, JA and Jawdat, O and Owegi, MA and Foster, LA and Vu, T and Ilieva, H and Newman, DS and Arcila-Londono, X and Jackson, CE and Ladha, S and Caress, JB and Swenson, A and Peltier, A and Lewis, RA and Fee, D and Elliott, M and Bedlack, R and Kasarskis, EJ and Elman, L and Rosenfeld, J and Walk, D and McIlduff, C and Twydell, P and Young, E and Johnson, K and Rezania, K and Goyal, NA and Cohen, JA and Benatar, M and Jones, V and Shah, J and Beydoun, SR and Wymer, JP and Zilliox, L and Nayar, S and Pattee, GL and Martinez-Thompson, J and Leitner, ML and Chen, K and Goldberg, YP and Cohen, Y and Geva, M and Hayden, MR and Paganoni, S and Cudkowicz, ME and , }, title = {Pridopidine in Amyotrophic Lateral Sclerosis: The HEALEY ALS Platform Trial.}, journal = {JAMA}, volume = {333}, number = {13}, pages = {1128-1137}, pmid = {40067755}, issn = {1538-3598}, abstract = {IMPORTANCE: Amyotrophic lateral sclerosis (ALS) is a fatal disease. The sigma-1 (σ1) receptor emerged as a target for intervention.

OBJECTIVE: To determine the effects of pridopidine, a σ1-receptor agonist, in ALS.

Pridopidine was tested as a regimen of the HEALEY ALS Platform Trial, a phase 2/3, multicenter, randomized, double-blind, platform trial. The study was conducted at 54 sites in the US from January 2021 to July 2022 (final follow-up, July 14, 2022). A total of 163 participants with ALS were randomized to receive pridopidine or placebo. An additional 122 concurrently randomized participants were assigned to receive placebo in other regimens and included in the analyses.

INTERVENTIONS: Eligible participants were randomized 3:1 to receive oral pridopidine 45 mg twice daily (n = 121) or matching oral placebo (n = 42) for a planned duration of 24 weeks.

MAIN OUTCOMES AND MEASURES: The primary efficacy outcome was change from baseline through week 24 in ALS disease severity, analyzed using a bayesian shared parameter model, which has components for function (Revised Amyotrophic Lateral Sclerosis Functional Rating Scale [ALSFRS-R]) and survival that were linked through an integrated estimate of treatment-dependent disease slowing across these 2 components. This was denoted as the disease rate ratio (DRR), with DRR less than 1 indicating a slowing in disease progression on pridopidine relative to placebo. There were 5 key secondary end points: time to 2-point or greater reduction in ALSFRS-R total score among participants with bulbar dysfunction at baseline, rate of decline in slow vital capacity among participants with bulbar dysfunction at baseline, percentage of participants with no worsening in the ALSFRS-R bulbar domain score, time to 1-point or greater change in the ALSFRS-R bulbar domain score, and time to death or permanent assisted ventilation.

RESULTS: Among 162 patients (mean age, 57.5 years; 35% female) who were randomized to receive the pridopidine regimen and included in the primary efficacy analysis, 136 (84%) completed the trial. In the primary analysis comparing pridopidine vs the combined placebo groups, there was no significant difference between pridopidine and placebo in the primary end point (DRR, 0.99 [95% credible interval, 0.80-1.21]; probability of DRR <1, 0.55) and no differences were seen in the components of ALSFRS-R or survival. There was no benefit of pridopidine on the secondary end points. In the safety dataset (pridopidine, n = 121; placebo, n = 163), the most common adverse events were falls (28.1% vs 29.3%, respectively) and muscular weakness (24.0% vs 31.7%, respectively).

CONCLUSIONS AND RELEVANCE: In this 24-week study, pridopidine did not impact the progression of ALS.

TRIAL REGISTRATION: ClinicalTrials.gov Identifiers: NCT04297683, NCT04615923.}, } @article {pmid40067754, year = {2025}, author = {, and Andrews, J and Paganoni, S and Macklin, EA and Chibnik, LB and Quintana, M and Saville, BR and Detry, MA and Vestrucci, M and Marion, J and McGlothlin, A and Young, E and Chase, M and Pothier, L and Harkey, B and Yu, H and Sherman, A and Shefner, J and Hall, M and Kittle, G and Connolly, MR and Berry, JD and D'Agostino, D and Tustison, E and Giacomelli, E and Scirocco, E and Alameda, G and Locatelli, E and Ho, D and Quick, A and Heitzman, D and Ajroud-Driss, S and Appel, SH and Shroff, S and Katz, J and Felice, K and Maragakis, NJ and Simmons, Z and Goutman, SA and Olney, N and Miller, T and Fernandes, JA and Ilieva, H and Jawdat, O and Weiss, MD and Foster, L and Vu, T and Ladha, S and Owegi, MA and Newman, DS and Arcila-Londono, X and Jackson, CE and Swenson, A and Heiman-Patterson, T and Caress, J and Fee, D and Peltier, A and Lewis, R and Rosenfeld, J and Walk, D and Johnson, K and Elliott, M and Kasarskis, EJ and Rutkove, S and McIlduff, CE and Bedlack, R and Elman, L and Goyal, NA and Rezania, K and Twydell, P and Benatar, M and Glass, J and Cohen, JA and Jones, V and Zilliox, L and Wymer, JP and Beydoun, SR and Shah, J and Pattee, GL and Martinez-Thompson, J and Nayar, S and Granit, V and Donohue, M and Grossman, K and Campbell, DJ and Qureshi, IA and Cudkowicz, ME and Babu, S}, title = {Verdiperstat in Amyotrophic Lateral Sclerosis: Results From the Randomized HEALEY ALS Platform Trial.}, journal = {JAMA neurology}, volume = {82}, number = {4}, pages = {333-343}, pmid = {40067754}, issn = {2168-6157}, mesh = {Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; *Amyotrophic Lateral Sclerosis/drug therapy ; Double-Blind Method ; *Enzyme Inhibitors/therapeutic use ; Treatment Outcome ; }, abstract = {IMPORTANCE: Myeloperoxidase is one of the most abundant peroxidase enzymes in activated myeloid cells. Myeloperoxidase inhibitors may have a clinical benefit in amyotrophic lateral sclerosis (ALS) by slowing neurodegeneration via reduced neuroinflammation and oxidative stress.

OBJECTIVE: To determine the safety, tolerability, and efficacy of verdiperstat, a selective myeloperoxidase inhibitor, in ALS.

Verdiperstat was tested as a regimen of the HEALEY ALS Platform Trial, a multicenter, double-blind, perpetual platform design, randomized clinical trial, with sharing of trial infrastructure and placebo data across multiple regimens. The study was conducted at 54 ALS referral centers across the US from July 2020 to April 2022. Adult participants with a diagnosis of clinically possible, probable, laboratory-supported probable, or definite ALS defined by the revised El Escorial criteria were randomized to verdiperstat or regimen-specific placebo. An additional group of participants concurrently randomized to placebo from other regimens was included in the analyses.

INTERVENTIONS: Eligible participants were randomized in a 3:1 ratio to receive oral verdiperstat, 600 mg, twice daily or matching placebo for a planned placebo-controlled duration of 24 weeks.

MAIN OUTCOMES AND MEASURES: The primary efficacy outcome was change from baseline through week 24 in disease severity, as measured by a joint model of ALS Functional Rating Scale-Revised and survival, with the treatment effect quantified by the disease rate ratio (DRR), with DRR less than 1 indicating a slowing in disease progression of verdiperstat relative to placebo.

RESULTS: A total of 167 participants (mean [SD] age, 58.5 [11.4] years; 59 [35.3%] female; 108 [64.6%] male) were randomized to either verdiperstat (126 [75.4%]) or to placebo (41 [25.6%]). Among the participants randomized to the verdiperstat regimen, 130 (78%) completed the trial. The estimated DRR was 0.98 (95% credible interval, 0.77-1.24; posterior probability = 0.57 for slowing of disease progression [DRR <1]). Verdiperstat was estimated to slow progression by 2% vs placebo (95% credible interval, -23% to 24%; posterior probability 0.57). Verdiperstat was overall safe and well tolerated. Common adverse events in the verdiperstat group were nausea, insomnia, and elevated thyrotropin levels.

CONCLUSIONS AND RELEVANCE: Results demonstrate that treatment with verdiperstat was unlikely to alter disease progression in ALS.

TRIAL REGISTRATION: Clinical Trial Identifiers: NCT04297683 and NCT04436510.}, } @article {pmid40066150, year = {2025}, author = {Stains, EL and Kennalley, AL and Tian, M and Boehnke, KF and Kraus, CK and Piper, BJ}, title = {Medical Cannabis in the United States: Comparing 2017 and 2024 State Qualifying Conditions to the 2017 National Academies of Sciences Report.}, journal = {Mayo Clinic proceedings. Innovations, quality & outcomes}, volume = {9}, number = {2}, pages = {100590}, pmid = {40066150}, issn = {2542-4548}, abstract = {OBJECTIVE: To compare the 2017 National Academies of Sciences, Engineering, and Medicine cannabis report to state medical cannabis (MC) laws defining approved qualifying conditions (QC) from 2017 and 2024 and to determine the evidence level of the QCs approved in each state.

PATIENTS AND METHODS: The 2017 National Academies of Sciences (NAS) report assessed therapeutic evidence for over 20 medical conditions treated with MC. We identified the QCs of 38 states (including Washington DC) where MC was legal in 2024 and compared them to the QCs listed by these states in 2017. The QCs were then categorized on the basis of NAS-established levels of evidence: limited, moderate, or substantial/conclusive evidence of effectiveness, limited evidence of ineffectiveness, or no/insufficient evidence to support or refute effectiveness. This study was completed from January 31, 2023 to June 20, 2024.

RESULTS: Most states listed at least one QC with substantial evidence-80.0% in 2017 and 97.0% in 2024. However, in 2024 only 8.3% of the QCs on states' QC lists met the standard of substantial/conclusive evidence. Of the 20 most popular QCs in the country in 2017 and 2024, one only (long-term pain) was categorized by the NAS as having substantial evidence for effectiveness. However, 7 were rated as either ineffective (eg, glaucoma) or insufficient evidence.

CONCLUSION: Most QCs lack evidence for use on the basis of the 2017 NAS report. Many states recommend QCs with little evidence (amyotrophic lateral sclerosis) or even those for which MC is ineffective (depression). These findings highlight a disparity between state-level MC recommendations and the evidence to support them.}, } @article {pmid40065593, year = {2025}, author = {Chen, S and Carter, D and Prier, J and Bingham, J and Patel, S and Kotay, M and Brockenbrough, PB and Gwathmey, K}, title = {Racial Disparities in ALS Progression: Time to Clinical Events Observed in a Single Center.}, journal = {Muscle & nerve}, volume = {71}, number = {6}, pages = {1086-1090}, pmid = {40065593}, issn = {1097-4598}, mesh = {Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; *Amyotrophic Lateral Sclerosis/ethnology/diagnosis/therapy ; Black or African American ; Disease Progression ; *Healthcare Disparities/ethnology ; Noninvasive Ventilation/statistics & numerical data ; Retrospective Studies ; Wheelchairs ; White ; }, abstract = {INTRODUCTION/AIMS: Studies examining racial differences in ALS have previously focused on diagnostic delay and disease severity. Time to critical clinical events has rarely been investigated, despite its importance in revealing differences in ALS patients' disease courses. This study explores racial disparities in time to specific clinical events in Black and non-Hispanic White ALS patients at a single center.

METHODS: We performed a retrospective analysis of 33 Black and 170 non-Hispanic White ALS patients examined at Virginia Commonwealth University between 2017 and 2023. Diagnosis dates, referral dates for wheelchair, noninvasive ventilation (NIV), augmentative and alternative communication (AAC) and hospice, along with demographic and clinical factors, were collected. We analyzed the racial difference for events occurring before or on the day of diagnosis using logistic regression models, and for events occurring after diagnosis using Cox proportional hazard models, adjusting for relevant demographic and clinical factors.

RESULTS: Black patients had significantly higher odds of acquiring a wheelchair (odds ratio = 4.06, p = 0.015) and NIV before diagnosis (odds ratio = 2.93, p = 0.017). Following diagnosis, Black patients had 1.72 times the hazards for wheelchair referral (p = 0.051), 2.17 times the hazard for NIV referral (p < 0.001), 1.84 times the hazard for AAC referral (p = 0.034), and 1.59 times the hazard for hospice referral (p = 0.24).

DISCUSSION: Our single-center findings demonstrate a large racial difference in time to clinical events for Black versus White ALS patients referred for NIV, AAC, hospice, and wheelchair, suggesting more advanced disease at the time of presentation or more rapid progression.}, } @article {pmid40065553, year = {2025}, author = {Boddy, SL and Simpson, RM and Walters, SJ and Walsh, T and McDermott, CJ and , and , }, title = {Further development of a patient-reported outcome measure to assess the impact of oral secretion problems in people living with MND.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {26}, number = {5-6}, pages = {507-515}, doi = {10.1080/21678421.2025.2469721}, pmid = {40065553}, issn = {2167-9223}, mesh = {Humans ; Male ; Female ; *Patient Reported Outcome Measures ; Middle Aged ; Aged ; Reproducibility of Results ; *Saliva/metabolism ; Longitudinal Studies ; *Amyotrophic Lateral Sclerosis/complications/diagnosis/physiopathology ; Adult ; Surveys and Questionnaires ; }, abstract = {Objective: Oral secretion problems are common yet poorly managed in people living with MND (plwMND). A validated patient-reported outcome for measuring saliva symptoms in this patient group would facilitate better monitoring of individuals. This study aimed to assess the validity, reliability and sensitivity to change of a revised version of the clinical saliva score for MND (CSS-MNDr). Methods: Data were collected as part of a longitudinal, observational saliva management study. The CSS-MNDr, ALS Functional Rating Scale, a Global Rating of Change questionnaire and saliva-specific modified Likert scale were completed at each study visit, each of which probed the severity of saliva symptoms. Construct validity, test-retest reliability and sensitivity of the CSS-MNDr were assessed and the minimal important difference of the instrument was estimated. Results: The CSS-MNDr showed excellent test-retest reliability (intraclass correlation coefficient >0.9). Construct validity showed the CSS-MNDr performed as expected, with bulbar-onset participants scoring significantly higher than those who reported limb-onset across all visits (group mean scores). Strong correlation of total scores with the ALSFRS-R saliva question was demonstrated (-0.8), with the thick subscore correlating less well (-0.5). A minimal important difference in the range of -2.5 to -3.6 over 3 months was estimated for worsening symptoms. Conclusions: The CSS-MNDr has been validated as a reliable patient reported outcome for measuring saliva problems in plwMND. With separate scores for thick and thin secretion problems, the CSS-MNDr is the most comprehensive tool for assessing salivary problems in plwMND reported to date.}, } @article {pmid40065552, year = {2025}, author = {Shibata, N and Kataoka, I and Okamura, Y and Murakami, K and Kato, Y and Yamamoto, T and Masui, K}, title = {Implications for soluble iron accumulation, oxidative stress, and glial glutamate release in motor neuron death associated with sporadic amyotrophic lateral sclerosis.}, journal = {Neuropathology : official journal of the Japanese Society of Neuropathology}, volume = {45}, number = {3}, pages = {177-201}, pmid = {40065552}, issn = {1440-1789}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/pathology/metabolism ; *Oxidative Stress/physiology ; *Iron/metabolism ; *Glutamic Acid/metabolism ; *Motor Neurons/metabolism/pathology ; Male ; Female ; Middle Aged ; Aged ; Spinal Cord/metabolism/pathology ; *Neuroglia/metabolism/pathology ; Cell Death/physiology ; Microglia/metabolism ; Animals ; Astrocytes/metabolism ; Aged, 80 and over ; }, abstract = {Oxidative stress in sporadic amyotrophic lateral sclerosis (ALS) has been evidenced by accumulation of oxidatively modified products of nucleic acids, lipids, sugars, and proteins in the motor neuron system of brains and spinal cords obtained at autopsy from the patients. We recently demonstrated soluble iron accumulation in activated microglia of sporadic ALS spinal cords. This finding could indicate that iron-mediated Fenton reaction is most likely to be responsible for oxidative stress associated with this disease. The excitatory amino acid neurotoxicity hypothesis for sporadic ALS has been proposed based on increased glutamate and aspartate concentrations in cerebrospinal fluid from the patients. Initially, the increase in extracellular excitatory amino acid levels was considered to reflect excessive release from the axon terminal of upper motor neurons. However, it is a question of whether the damaged upper motor neurons continue releasing glutamate even in advanced stage of this disease. To address this issue, we hypothesized that glial cells might be a glutamate release source. Our immunohistochemical analysis on autopsied human spinal cords revealed that ferritin, hepcidin, ferroportin, aconitase 1, tumor necrosis factor-α (TNF-α), TNF-α-converting enzyme (TACE), and glutaminase-C (GAC) were expressed mainly in microglia and that cystine/glutamate antiporter (xCT) was expressed mainly in astrocytes. We next performed cell culture experiments. Cultured microglia treated with soluble iron over-released glutamate and TNF-α via aconitase 1 and TACE, respectively. Cultured microglia treated with TNF-α over-released glutamate via GAC. Cultured microglia treated with hepcidin, of which expression is known to be upregulated by TNF-α, showed downregulated expression of ferroportin. Cultured astrocytes treated with hydrogen peroxide over-released glutamate via xCT. These observations provide in vivo and in vitro evidence that microglia and astrocytes are glutamate suppliers in response to soluble iron overload and oxidative stress, respectively, in sporadic ALS.}, } @article {pmid40064496, year = {2025}, author = {Su, Y and Yang, F and Xie, JC and Zhang, C and Luo, RX and Li, WS and Liu, BL and Su, MZ}, title = {Electroacupuncture Neural Stimulation Mitigates Bladder Dysfunction and Mechanical Allodynia in Cyclophosphamide Induced Cystitis through Downregulation of the BDNF-TrkB Signaling Pathway.}, journal = {eNeuro}, volume = {12}, number = {3}, pages = {}, pmid = {40064496}, issn = {2373-2822}, abstract = {Central sensitization plays a critical role in bladder pain syndrome/interstitial cystitis (BPS/IC). Electroacupuncture (EA) nerve stimulation therapy has been broadly acknowledged as an effective means of alleviating chronic pathological pain. However, it remains to be explored whether EA is effective in mitigating pain-sensitive symptoms of BPS/IC and the mechanisms involved. This study aims to investigate the analgesic effect and mechanism of EA therapy. To achieve this goal, we employed several techniques: mechanical pain threshold tests to assess pain sensitivity, urodynamic studies to evaluate bladder function, Western blotting (WB) for protein analysis, immunofluorescence for visualizing, and transcriptomics. A rat cystitis model was established through a systemic intraperitoneal injection with cyclophosphamide (CYP). EA therapy was executed by stimulating the deep part of the hypochondriac point, where the 2nd-4th sacral nerves traverse. EA treatment was observed to effectively reduce mechanical allodynia, enhance urinary function, suppress the activation of microglial cells, and alleviate neuroinflammation. Additionally, EA demonstrated the capability to downregulate BDNF-TrkB signal transduction in the spinal dorsal horn. Transcriptome sequencing has indicated that EA therapy potentially inhibits excitatory neural transmission and modulates several pathways related to longevity. Furthermore, EA therapy has shown efficacy in treating conditions such as Huntington's disease, amyotrophic lateral sclerosis, and prion diseases. In conclusion, by regulating the BDNF-TrkB signaling, EA nerve stimulation can effectively alleviate bladder dysfunction and mechanical allodynia in cyclophosphamide-induced cystitis model. Our research elucidates the underlying mechanisms of EA therapy in treating bladder dysfunction and offers new theoretical insights for addressing painful sensitization in BPS.Significance Statement Central sensitization is a major factor in bladder pain syndrome/interstitial cystitis (BPS/IC), making effective pain management crucial. This study explores the potential of electroacupuncture (EA) as a therapeutic approach to alleviate pain and improve bladder function in a rat model of BPS/IC induced by cyclophosphamide. Our findings demonstrate that EA therapy significantly reduces mechanical allodynia, enhances urinary function, and decreases neuroinflammation by modulating BDNF-TrkB signaling in the spinal dorsal horn. The research highlights EA's capability to inhibit excitatory neural transmission and provide relief in chronic pain conditions. These results offer new insights into the mechanisms of EA therapy, potentially improving treatment strategies for BPS/IC and similar pain syndromes.}, } @article {pmid40064491, year = {2025}, author = {Izumi, Y and Nakayama, Y}, title = {[Communicating the Diagnosis of Amyotrophic Lateral Sclerosis].}, journal = {Brain and nerve = Shinkei kenkyu no shinpo}, volume = {77}, number = {3}, pages = {259-263}, doi = {10.11477/mf.188160960770030259}, pmid = {40064491}, issn = {1881-6096}, mesh = {*Amyotrophic Lateral Sclerosis/diagnosis/psychology ; Humans ; *Communication ; }, abstract = {When explaining amyotrophic lateral sclerosis, family members, caregivers, and other professionals are encouraged to be present with the patient's consent. Patients' perceptions vary considerably depending on their condition, personality, and home environment; therefore, the content of the explanation should be carefully considered. If the patient did not fully understand or provide consent to participate, the explanation was repeated. Depending on the patient's level of understanding and acceptance, we provided step-by-step explanations. The patients were informed that the decision could change later, even after the treatment plan had been decided. In explanations involving a multidisciplinary team, each professional explains; however, it is also important for the team leader to understand the patient's perceptions.}, } @article {pmid40063887, year = {2025}, author = {Hayden, CD and Murphy, BP and Gilsenan, D and Nasseroleslami, B and Hardiman, O and Murray, D}, title = {Clinical validation of a novel hand dexterity measurement device.}, journal = {PLOS digital health}, volume = {4}, number = {3}, pages = {e0000744}, pmid = {40063887}, issn = {2767-3170}, abstract = {The lack of sensitive objective outcome measures for hand dexterity is a barrier for clinical assessment of neurological conditions and has negatively affected clinical trials. Here, we clinically validate a new method for measuring hand dexterity, a novel hand worn sensor that digitises the Finger Tapping Test. The device was assessed in a cohort of 180 healthy controls and 51 people with Amyotrophic Lateral Sclerosis (ALS) and compared against rating scales and traditional measures (Nine Hole Peg test and grip dynamometry). 14 features were extracted from the device and using a logistic regression algorithm, a 0-100 dexterity performance score was generated for each participant, which accounted for age/sex differences. The device returned objective ratings of a participant's hand dexterity (dominant, non-dominant and overall score). The average overall dexterity performance score in all healthy participants was 88 ± 17 (mean ± standard deviation). The overall dexterity score was statistically significantly worse in participants with ALS (age/sex matched healthy subset: 80 ± 20, ALS: 45 ± 32, p-value < 0.0001). The device also had a higher completion rate, (94% dominant hand) compared to the traditional measures (82% dominant hand). This test and scoring system have been validated and the regression model was developed using a framework that is potentially applicable to any relevant condition. This device could act as an objective outcome measure in clinical trials and may be useful in improving patient care.}, } @article {pmid40063831, year = {2025}, author = {Kubinski, S and Claus, L and Schüning, T and Zeug, A and Kalmbach, N and Staege, S and Gschwendtberger, T and Petri, S and Wegner, F and Claus, P and Hensel, N}, title = {Aggregates associated with amyotrophic lateral sclerosis sequester the actin-binding protein profilin 2.}, journal = {Human molecular genetics}, volume = {34}, number = {10}, pages = {882-893}, doi = {10.1093/hmg/ddaf020}, pmid = {40063831}, issn = {1460-2083}, support = {ZE994//Deutsche Forschungsgemeinschaft/ ; }, mesh = {*Profilins/metabolism/genetics ; *Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology ; Humans ; RNA-Binding Protein FUS/genetics/metabolism ; C9orf72 Protein/genetics/metabolism ; Protein Aggregates ; Mutation ; Stress Granules/metabolism/genetics ; Motor Neurons/metabolism/pathology ; Actin Cytoskeleton/metabolism/genetics ; Superoxide Dismutase-1/genetics/metabolism ; DNA-Binding Proteins/genetics/metabolism ; Actins/metabolism/genetics ; Protein Aggregation, Pathological/genetics ; }, abstract = {Amyotrophic Lateral Sclerosis (ALS) is a devastating neurodegenerative disease characterized by the degeneration of upper and lower motoneurons. The four most frequently mutated genes causing familial ALS (fALS) are C9orf72, FUS, SOD1, and TARDBP. Some of the related wild-type proteins comprise intrinsically disordered regions (IDRs) which favor their assembly in liquid droplets-the biophysical mechanism behind the formation of physiological granules such as stress granules (SGs). SGs assemble and dissolve dependent on the cellular condition. However, it has been suggested that transition from reversible SGs to irreversible aggregates contributes to the toxic properties of ALS-related mutated proteins. Sequestration of additional proteins within these aggregates may then result in downstream toxicity. While the exact downstream mechanisms remain elusive, rare ALS-causing mutations in the actin binding protein profilin 1 suggest an involvement of the actin cytoskeleton. Here, we hypothesize that profilin isoforms become sequestered in aggregates of ALS-associated proteins which induce subsequent dysregulation of the actin cytoskeleton. Interestingly, localization of neuronal profilin 2 in SGs was more pronounced compared with the ubiquitously expressed profilin 1. Accordingly, FUS and C9orf72 aggregates prominently sequestered profilin 2 but not profilin 1. Moreover, we observed a distinct sequestration of profilin 2 and G-actin to C9orf72 aggregates in different cellular models. On the functional level, we identified dysregulated actin dynamics in cells with profilin 2-sequestering aggregates. In summary, our results suggest a more common involvement of profilins in ALS pathomechanisms than indicated from the rarely occurring profilin mutations.}, } @article {pmid40061974, year = {2025}, author = {Zhang, ZN and Hao, L and Han, S and Li, SS and Lin, SX and Miao, YD}, title = {Harnessing the prognostic power of preoperative systemic immune-inflammation index/albumin ratio in hepatocellular carcinoma resection.}, journal = {World journal of gastrointestinal surgery}, volume = {17}, number = {2}, pages = {102261}, pmid = {40061974}, issn = {1948-9366}, abstract = {The recent study by Chen et al, published in the World Journal of Gastroenterology, introduces a groundbreaking assessment tool-the preoperative systemic immune-inflammation index/albumin (SII/ALB) ratio-for patients with hepatocellular carcinoma (HCC) undergoing curative resection. This study not only establishes the independent prognostic significance of the SII/ALB ratio but also incorporates it into a predictive nomogram, enhancing its utility for clinical decision-making. The SII/ALB ratio, by integrating inflammatory and nutritional biomarkers, offers a novel lens through which the prognosis of HCC patients can be viewed, suggesting a more tailored approach to patient management. The development of the nomogram, validated for its accuracy in predicting patient outcomes, marks a pivotal advance, potentially guiding surgical decisions and postoperative care. However, the study's focus on a single-center cohort prompts the need for validation in a broader, more diverse patient population to ensure its applicability across various clinical settings. Moreover, longitudinal studies could elucidate the dynamic changes in SII/ALB post-surgery, offering insights into its potential as a continuous monitor for recurrence and long-term survival. This abstract aim to underscore the critical findings of Chen et al's study while calling for further research to explore the full potential of the SII/ALB ratio in the global management of hepatocellular carcinoma.}, } @article {pmid40061972, year = {2025}, author = {Yi, XM and Cai, HQ and Jiao, Y}, title = {Programmed cell death receptor 1 inhibitor Pembrolizumab in the treatment of advanced gastric cancer.}, journal = {World journal of gastrointestinal surgery}, volume = {17}, number = {2}, pages = {100257}, pmid = {40061972}, issn = {1948-9366}, abstract = {This editorial discusses Christodoulidis et al's article, which appeared in the most recent edition. The clinical trials have demonstrated the programmed cell death receptor 1 (PD-1) inhibitor Pembrolizumab involved combination therapy can improve the efficacy of advanced gastric cancer (AGC). Pembrolizumab combined with chemotherapy can enhance its sensitivity, and further eliminate tumor cells that develop resistance to chemotherapy. The combination of Pembrolizumab and Trastuzumab targeting human epidermal growth factor receptor 2 showed improved prognosis. The overall toxic effects of Pembrolizumab are significantly lower than traditional chemotherapy, and the safety is controllable. PD-1 inhibitor Pembrolizumab sheds a light on the treatment of AGC and brings new hope to the clinical practice.}, } @article {pmid40061966, year = {2025}, author = {Wang, H and Jiao, Y and Ma, Q and Liu, YH}, title = {Overview of endoscopic biliary stenting in malignant obstructive jaundice.}, journal = {World journal of gastrointestinal surgery}, volume = {17}, number = {2}, pages = {103378}, pmid = {40061966}, issn = {1948-9366}, abstract = {This article discusses Wang et al's essay. Endoscopic biliary stenting, a less invasive alternative to surgery, is effective for malignant obstructive jaundice. This article summarizes the pathophysiology of biliary obstruction, the technical aspects of stenting, and the clinical outcomes. By comparison of endoscopic stenting with percutaneous biliary drainage, improvements and complications are focused on. Additionally, patient selection for stenting and future advancements in stent technology are important. Overall, endoscopic biliary stenting is a valuable palliative option for patients with malignant jaundice, especially those ineligibles for surgery.}, } @article {pmid40060668, year = {2025}, author = {Axakova, A and Ding, M and Cote, AG and Subramaniam, R and Senguttuvan, V and Zhang, H and Weile, J and Douville, SV and Gebbia, M and Al-Chalabi, A and Wahl, A and Reuter, J and Hurt, J and Mitchell, A and Fradette, S and Andersen, PM and van Loggerenberg, W and Roth, FP}, title = {Landscapes of missense variant impact for human superoxide dismutase 1.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {40060668}, issn = {2692-8205}, support = {RM1 HG010461/HG/NHGRI NIH HHS/United States ; UM1 HG011989/HG/NHGRI NIH HHS/United States ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive motor neuron disease for which important subtypes are caused by variation in the Superoxide Dismutase 1 gene SOD1. Diagnosis based on SOD1 sequencing can not only be definitive but also indicate specific therapies available for SOD1-associated ALS (SOD1-ALS). Unfortunately, SOD1-ALS diagnosis is limited by the fact that a substantial fraction (currently 26%) of ClinVar SOD1 missense variants are classified as "variants of uncertain significance" (VUS). Although functional assays can provide strong evidence for clinical variant interpretation, SOD1 assay validation is challenging, given the current incomplete and controversial understanding of SOD1-ALS disease mechanism. Using saturation mutagenesis and multiplexed cell-based assays, we measured the functional impact of over two thousand SOD1 amino acid substitutions on both enzymatic function and protein abundance. The resulting 'missense variant effect maps' not only reflect prior biochemical knowledge of SOD1 but also provide sequence-structure-function insights. Importantly, our variant abundance assay can discriminate pathogenic missense variation and provides new evidence for 41% of missense variants that had been previously reported as VUS, offering the potential to identify additional patients who would benefit from therapy approved for SOD1-ALS.}, } @article {pmid40060539, year = {2025}, author = {Petrescu, J and Roque, CG and Jackson, CA and Daly, A and Kang, K and Casel, O and Leung, M and Reilly, L and Eschbach, J and McDade, K and Gregory, JM and Bonneau, R and Smith, C and Phatnani, H}, title = {Distinct Cellular Phenotypes of Language and Executive Decline in Amyotrophic Lateral Sclerosis.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2025.02.26.640433}, pmid = {40060539}, issn = {2692-8205}, abstract = {Cognitive manifestations, including impairment in language and executive functions, are seen in amyotrophic lateral sclerosis (ALS), but the mechanisms that underlie these deficits remain unclear. To address this, we mapped prefrontal cortex regions from ALS patients by integrating spatial and single-nucleus transcriptomics in a cognitively stratified patient cohort. We uncover that cognitive impairment in ALS is associated with distinct patterns of neuronal dysfunction and glial-vascular dysregulation that vary by region and cognitive subtype. Executive dysfunction is linked to reduced mitochondrial and synaptic activity in neurons localized to the deeper layers of the dorsolateral prefrontal cortex, whereas language-related deficits track with a more diffuse, pan-regional response involving both glial and vascular abnormalities. Our analyses also identify signatures in the prefrontal cortex that span both motor and cognitive phenotypes, including a multicellular gliosis response. The findings reveal that the clinical heterogeneity of ALS is driven by phenotype-specific molecular and cellular interactions in motor and non-motor regions of the brain.}, } @article {pmid40060442, year = {2025}, author = {Deng, X and Bradshaw, G and Kalocsay, M and Mitchison, T}, title = {Tubulin Regulates the Stability and Localization of STMN2 by Binding Preferentially to Its Soluble Form.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {40060442}, issn = {2692-8205}, support = {R35 GM131753/GM/NIGMS NIH HHS/United States ; }, abstract = {Loss of the tubulin-binding protein STMN2 is implicated in amyotrophic lateral sclerosis (ALS) but how it protects neurons is not known. STMN2 is known to turn over rapidly and accumulate at axotomy sites. We confirmed fast turnover of STMN2 in U2OS cells and iPSC-derived neurons and showed that degradation occurs mainly by the ubiquitin-proteasome system. The membrane targeting N-terminal domain of STMN2 promoted fast turnover, whereas its tubulin binding stathmin-like domain (SLD) promoted stabilization. Proximity labeling and imaging showed that STMN2 localizes to trans-Golgi network membranes and that tubulin binding reduces this localization. Pull-down assays showed that tubulin prefers to bind to soluble over membrane-bound STMN2. Our data suggest that STMN2 interconverts between a soluble form that is rapidly degraded unless bound to tubulin and a membrane-bound form that does not bind tubulin. We propose that STMN2 is sequestered and stabilized by tubulin binding, while its neuroprotective function depends on an unknown molecular activity of its membrane-bound form.}, } @article {pmid40060160, year = {2025}, author = {Mangalindan, KE and Wyatt, TR and Brown, KR and Shapiro, M and Maggio, LA}, title = {Investigating the Road to Equity: A Scoping Review of Solutions to Mitigate Implicit Bias in Assessment within Medical Education.}, journal = {Perspectives on medical education}, volume = {14}, number = {1}, pages = {92-106}, pmid = {40060160}, issn = {2212-277X}, mesh = {Humans ; *Education, Medical/methods/standards ; *Bias, Implicit ; *Educational Measurement/methods/standards ; }, abstract = {INTRODUCTION: In medical education, assessments have high-stakes implications. Yet, assessments are rife with unconscious bias, which contributes to inequitable social structures. Implicit bias in assessment must be addressed because medical educators use assessments to guide learning and promote development of physicians' careers. In this scoping review, the authors map the literature on implicit bias in assessment, as it applies to: 1) the types of implicit bias addressed, 2) the targets and types of interventions studied or proposed, and 3) how publications describe intervention efficacy.

METHODS: The authors conducted a scoping review of the literature on interventions to mitigate implicit bias that was published between January 2010 and August 2023. Author pairs independently screened articles for inclusion and extracted data. Discrepancies were resolved with discussion and consensus. Qualitative and quantitative analysis was informed by Anderson et al's three assessment orientations: fairness, assessment for inclusion (AfI), and justice.

RESULTS: 7,831 articles were identified; 54 articles were included. The majority (n = 37; 69%) of articles focus on implicit bias toward those underrepresented in medicine. Interventions to mitigate implicit bias were targeted toward admissions and applications, faculty training, recruitment, summative assessments, and evaluation templates. Interventions had fairness (n = 43; 96%) and AfI (n = 22; 49%) orientations; no articles used a justice-orientation. For the sub-set of research studies (n = 40), almost all (n = 34; 85%) examined a single program/institution.

DISCUSSION: This scoping review showed that more work is necessary to address different types of implicit biases, move scholarship beyond single-institution studies, refine existing interventions, and evaluate how efficacy is defined.}, } @article {pmid40059194, year = {2025}, author = {Shang, Q and Zhou, J and Ye, J and Chen, M}, title = {Adverse events reporting of edaravone: a real-world analysis from FAERS database.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {8148}, pmid = {40059194}, issn = {2045-2322}, mesh = {*Edaravone/adverse effects ; Humans ; *Adverse Drug Reaction Reporting Systems/statistics & numerical data ; Databases, Factual ; United States ; *Amyotrophic Lateral Sclerosis/drug therapy ; United States Food and Drug Administration ; Male ; Female ; Bayes Theorem ; *Drug-Related Side Effects and Adverse Reactions/epidemiology ; }, abstract = {For individuals with amyotrophic lateral sclerosis (ALS), intravenous edaravone is approved as a disease-modifying medication; yet, there have been many reports of adverse events (AEs). We examined the AEs associated with edaravone in this study using actual data from the FDA's (Food and Drug Administration) adverse event reporting system (FAERS). By extracting large-scale data from the FAERS database, this study used the signals of edaravone-associated AEs were quantified using the multiitem gamma Poisson shrinker (MGPS) method based on disproportionality, the Bayesian confidence propagation neural network (BCPNN), the reporting odds ratio (ROR), and the proportional reporting ratio (PRR). In the FAERS database, this study extracted data between April 2017 and March 2024, and edaravone was identified as the "primary suspect (PS)" in 2,986 AE reports. AEs associated with edaravone specifically targeted 27 system organ types (SOCs). Unexpectedly serious AEs that weren't mentioned in the drug insert, include abnormal hepatic function, catheter site thrombosis, pain, cerebral hemorrhage, infection, cerebral infarction, poor venous access, disseminated intravascular coagulation, vein collapse and cerebral venous sinus thrombosis. Our research found possible signals of new AEs that may offer substantial backing for clinical surveillance and edaravone risk assessment, but further research and validation are needed, especially for those AE that may occur in actual usage scenarios but are not yet explicitly described in the instruction.}, } @article {pmid40030015, year = {2025}, author = {Johnson, EA and Nowar, R and Viola, KL and Huang, W and Zhou, S and Bicca, MA and Zhu, W and Kranz, DL and Klein, WL and Silverman, RB}, title = {Inhibition of amyloid beta oligomer accumulation by NU-9: A unifying mechanism for the treatment of neurodegenerative diseases.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {122}, number = {10}, pages = {e2402117122}, pmid = {40030015}, issn = {1091-6490}, support = {R01 AG061708/AG/NIA NIH HHS/United States ; R56 AG050492/AG/NIA NIH HHS/United States ; AG061708//HHS | National Institutes of Health (NIH)/ ; AG050492//HHS | National Institutes of Health (NIH)/ ; }, mesh = {*Amyloid beta-Peptides/metabolism ; Humans ; Animals ; *Neurodegenerative Diseases/drug therapy/metabolism/pathology ; Neurons/metabolism/drug effects ; Hippocampus/metabolism/drug effects ; Mice ; Autophagy/drug effects ; Protein Aggregation, Pathological/drug therapy/metabolism ; Alzheimer Disease/metabolism/drug therapy ; Lysosomes/metabolism ; Protein Aggregates/drug effects ; }, abstract = {Protein aggregation is a hallmark of neurodegenerative diseases, which connects these neuropathologies by a common phenotype. Various proteins and peptides form aggregates that are poorly degraded, and their ensuing pathological accumulation underlies these neurodegenerative diseases. Similarities may exist in the mechanisms responsible for the buildup of these aggregates. Therefore, therapeutics designed to treat one neurodegenerative disease may be beneficial to others. In ALS models, the compound NU-9 was previously shown to block neurodegeneration produced by aggregation-inducing mutations of SOD-1 and TDP-43 [B. Genç et al., Clin. Transl. Med. 11, e336 (2021)]. Here, we report that NU-9 also prevents the accumulation of amyloid beta oligomers (AβOs), small peptide aggregates that are instigators of Alzheimer's disease neurodegeneration [M. Tolar et al., Int. J. Mol. Sci. 22, 6355 (2021)]. AβO buildup was measured by immunofluorescence imaging of cultured hippocampal neurons exposed to exogenous monomeric Aβ. In this model, AβO buildup occurs via cathepsin L- and dynamin-dependent trafficking. This is prevented by NU-9 through a cellular mechanism that is cathepsin B- and lysosome-dependent, suggesting that NU-9 enhances the ability of endolysosomal trafficking to protect against AβO buildup. This possibility is strongly supported by a quantitative assay for autophagosomes that shows robust stimulation by NU-9. These results contribute additional understanding to the mechanisms of protein aggregation and suggest that multiple neurodegenerative diseases might be treatable by targeting common pathogenic mechanisms responsible for protein aggregation.}, } @article {pmid40057796, year = {2025}, author = {Mitra, J and Kodavati, M and Dharmalingam, P and Guerrero, EN and Rao, KS and Garruto, RM and Hegde, ML}, title = {Endogenous TDP-43 mislocalization in a novel knock-in mouse model reveals DNA repair impairment, inflammation, and neuronal senescence.}, journal = {Acta neuropathologica communications}, volume = {13}, number = {1}, pages = {54}, pmid = {40057796}, issn = {2051-5960}, support = {R03AG064266/AG/NIA NIH HHS/United States ; RF1NS112719/NS/NINDS NIH HHS/United States ; RF1 NS112719/NS/NINDS NIH HHS/United States ; R01 NS088645/NS/NINDS NIH HHS/United States ; R03 AG064266/AG/NIA NIH HHS/United States ; }, mesh = {Animals ; *DNA-Binding Proteins/metabolism/genetics ; Mice ; Disease Models, Animal ; Gene Knock-In Techniques ; *Cellular Senescence/physiology/genetics ; Mice, Transgenic ; *DNA Repair/physiology/genetics ; *Motor Neurons/pathology/metabolism ; Inflammation/pathology/metabolism/genetics ; *TDP-43 Proteinopathies/pathology/genetics/metabolism ; }, abstract = {TDP-43 mislocalization and aggregation are key pathological features of amyotrophic lateral sclerosis (ALS)- and frontotemporal dementia (FTD). However, existing transgenic hTDP-43 WT or ∆NLS-overexpression animal models primarily focus on late-stage TDP-43 proteinopathy. To complement these models and to study the early-stage motor neuron-specific pathology during pre-symptomatic phases of disease progression, we generated a new endogenous knock-in (KI) mouse model using a combination of CRISPR/Cas9 and FLEX Cre-switch strategy for the conditional expression of a mislocalized Tdp-43∆NLS variant of mouse Tdp-43. This variant is expressed either in the whole body (WB) or specifically in the motor neurons (MNs) in two distinct models. These mice exhibit loss of nuclear Tdp-43, with concomitant cytosolic accumulation and aggregation in targeted cells, leading to increased DNA double-strand breaks (DSBs), signs of inflammation, and associated cellular senescence. Notably, unlike WT Tdp-43, which functionally interacts with Xrcc4 and DNA Ligase 4, the key DSB repair proteins in the non-homologous end-joining (NHEJ) pathway, the Tdp-43∆NLS mutant sequesters them into cytosolic aggregates, exacerbating neuronal damage in mouse brain. The mutant mice also exhibit myogenic degeneration in hindlimb soleus muscles and distinct motor deficits, consistent with the characteristics of motor neuron disease (MND). Our findings reveal progressive degenerative mechanisms in motor neurons expressing endogenous Tdp-43∆NLS mutant, independent of Tdp-43 overexpression or other confounding factors. Thus, this unique Tdp-43 KI mouse model, which displays key molecular and phenotypic features of Tdp-43 proteinopathy, offers a significant opportunity to characterize the early-stage progression of MND further and also opens avenues for developing DNA repair-targeted approaches for treating TDP-43 pathology-linked neurodegenerative diseases.}, } @article {pmid40057753, year = {2025}, author = {Sharbafshaaer, M and Siciliano, M and Passaniti, C and Sant'Elia, V and Silvestro, M and Russo, A and Esposito, S and Tedeschi, G and Trojano, L and Trojsi, F}, title = {Screening of visuospatial abilities in amyotrophic lateral sclerosis (ALS): a pilot study using the battery for visuospatial abilities (BVA).}, journal = {Orphanet journal of rare diseases}, volume = {20}, number = {1}, pages = {110}, pmid = {40057753}, issn = {1750-1172}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology/diagnosis ; Male ; Female ; Pilot Projects ; Middle Aged ; Aged ; Neuropsychological Tests ; Space Perception/physiology ; Adult ; Visual Perception/physiology ; }, abstract = {BACKGROUND: Cognitive deficits related to frontotemporal dysfunction are common in Amyotrophic Lateral Sclerosis (ALS). Visuospatial deficits, related to posterior cerebral regions, are often underestimated in ALS, though they play a crucial role in attending daily living activities. Our pilot study aims at assessing visuospatial abilities using a domain-specific tool in ALS patients compared to healthy controls (HC).

METHODS: Twenty-three patients with early ALS and 23 age- and education-matched HC underwent the Battery for Visuospatial Abilities (BVA), including 4 visuo-perceptual and 4 visuo-representational subtests.

RESULTS: When compared to HC, ALS scored worse in 2 visuo-perceptual subtests (i.e., Line Length Judgment and Line Orientation Judgment) and 1 visuo-representational tasks (i.e., Hidden Figure Identification, HFI) (p < 0.01). No correlations arose between ALS clinical features and BVA performance. More than 80% of the ALS cohort obtained abnormal scores in the HFI subtest.

CONCLUSIONS: Our findings revealed that patients with ALS scored worse (compared to HC) on selective tests tapping "perceptual" and "representational" visuospatial abilities, since the early stages of disease. In clinical practice, our findings highlight the need for multi-domain neuropsychological assessment, for monitoring disease courses and properly organizing care management of patients with ALS.}, } @article {pmid40057669, year = {2025}, author = {Hatcher, H and Stankeviciute, S and Learn, C and Qu, AX}, title = {Regulatory, Translational, and Operational Considerations for the Incorporation of Biomarkers in Drug Development.}, journal = {Therapeutic innovation & regulatory science}, volume = {59}, number = {3}, pages = {519-526}, pmid = {40057669}, issn = {2168-4804}, mesh = {*Drug Development/legislation & jurisprudence ; Humans ; *Biomarkers ; United States ; United States Food and Drug Administration ; Drug Approval ; }, abstract = {BACKGROUND: Biomarkers are an integral component in the drug development paradigm. According to the US Food and Drug Administration (FDA), a biomarker is "a defined characteristic that is measured as an indicator of normal biological processes, pathogenic processes, or biological responses to an exposure or intervention, including therapeutic intervention" (FDA-NIH Biomarker Working Group. BEST (Biomarkers, EndpointS, and other Tools) Resource [Internet]. Silver Spring (MD): Food and Drug Administration (US); 2016-. Glossary. 2016 [Updated 2021 Nov 29, cited 2024 Apr 14]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK338448/ Co-published by National Institutes of Health (US), Bethesda (MD)). The European Medicines Agency (EMA) defines a biomarker as "an objective and quantifiable measure of a physiological process, pathological process or response to a treatment (excluding measurements of how an individual feels or functions" European Medicines Agency (EMA). Biomaker. 2020a. Available from: https://www.ema.europa.eu/en/glossary-terms/biomarker#:~:text=Biomarker-,Biomarker,an%20individual%20feels%20or%20functions . Several clinical biomarkers are well-documented and have been used routinely for decades in health care settings and have long been accepted as valid endpoints for drug approval (for example, blood pressure measurement as a biomarker for cardiovascular health) (European Medicines Agency (EMA). Assessment report, TAGRISSO. 2016. Available from: https://www.ema.europa.eu/en/documents/assessment-report/tagrisso-epar-public-assessment-report_en.pdf . Accessed 15 Apr 2024). Recently, novel biomarkers have been identified and validated to accelerate developing innovative therapies indicated for serious human diseases, for example targeted/immune therapies of cancer (Chen in Med Drug Discov 21:100174, 2024). As indicators of the efficacy of new pharmacological treatments or therapeutic interventions, biomarkers can improve clinical trial efficacy and reduce uncertainty in regulatory decision making (Bakker et al. in Clin Pharmacol Ther 112:69-80, 2022; Califf in Exp Biol Med 243:213-221, 2018; Parker et al. in Cancer Med 10:1955-1963, 2021).

METHODOLOGY: This article describes case studies of recent drug approvals that successfully leveraged validated and non-validated biomarkers (i.e., tofersen for the neurodegenerative disease amyotrophic lateral sclerosis (ALS) in adults; and osimertinib for treatment of patients with metastatic epidermal growth factor receptor (EGFR) T790M mutation-positive non-small cell lung cancer (NSCLC)).

CONCLUSIONS: Best practices for biomarker selection and strategies for health authority biomarker qualification programs are presented along with an overview of current limitations and challenges to optimizing biomarker applications along the drug development continuum from regulatory, translational, and operational perspectives.}, } @article {pmid40056685, year = {2025}, author = {Jakhar, M and Barone, V}, title = {Single atom catalysts adsorbed on reduced monolayers for enhanced kinetics in Al-S batteries.}, journal = {Journal of colloid and interface science}, volume = {689}, number = {}, pages = {137226}, doi = {10.1016/j.jcis.2025.03.015}, pmid = {40056685}, issn = {1095-7103}, abstract = {Rechargeable aluminum-sulfur (Al-S) batteries have attracted significant attention as potential next-generation energy storage devices due to their safety, the natural abundance of the elemental components, and high theoretical energy density. However, their utilization is hindered by sluggish reaction kinetics and poor reversibility. Introducing single-atom catalysts (SACs) can promote redox processes at the cathode and help in mitigating the shuttle effect of Al polysulfides (Al2Sx). While the electrochemical, thermodynamic, and thermal stabilities of SACs (Co, Fe, Ir, Ni, Pt, and Rh) have been explored in previous studies, this work focuses on their potential role in enhancing reaction kinetics in Al-S batteries. Our calculations indicate that SACs-based substrates exhibit more robust binding energies for capturing Al2Sx than the bare surfaces. Additionally, SACs lower the free energies associated with the rate-determining step during discharging and exhibit lower decomposition barriers during charging. Moreover, the interaction of soluble Al2Sx with the electrolyte reveals that SAC supported polysulfides are less likely to dissolve in the electrolyte than their pristine counterparts. The analysis of the underlying mechanisms of the interaction of molecules and the Co@ substrate reveals the ability of this substrate to accommodate large volume changes and support a sulfur loading up to 53.37 wt% during the charging and discharging cycles, without causing fractures. The mechanism driving this enhanced performance is extensively investigated through charge transfer, bond strength, and d-band center analyses. Our findings present an effective strategy for designing SACs substrates to improve the electrochemical performance of Al-S cathodes.}, } @article {pmid40056552, year = {2025}, author = {Newell, ME and Babbrah, A and Aravindan, A and Kulkarni, S and Ellershaw, A and Dupati, A and Rathnam, R and Shaffer, G and Estrada, L and Curtis, C and Leneaux, J and Driver, EM and Halden, RU}, title = {Wastewater-borne markers of neurodegenerative disease: β-methylamino-L-alanine and aminomethylphosphonic acid.}, journal = {The Science of the total environment}, volume = {970}, number = {}, pages = {179032}, doi = {10.1016/j.scitotenv.2025.179032}, pmid = {40056552}, issn = {1879-1026}, mesh = {*Amino Acids, Diamino/analysis ; *Wastewater/chemistry/analysis ; Biomarkers/analysis ; *Water Pollutants, Chemical/analysis ; Cyanobacteria Toxins ; *Environmental Monitoring/methods ; *Neurodegenerative Diseases/epidemiology ; Humans ; Glycine/analogs & derivatives/analysis ; Glyphosate ; Tandem Mass Spectrometry ; Chromatography, Liquid ; Isoxazoles/analysis ; Organophosphonates ; }, abstract = {Exposure to toxic organic chemicals such as β-methylamino-L-alanine (BMAA) and glyphosate has been associated with neurodegenerative diseases (NDDs), including amyotrophic lateral sclerosis (ALS), Parkinson's Disease (PD), and Alzheimer's Disease (AD). We explored the utility of BMAA and glyphosate's metabolite aminomethylphosphonic acid (AMPA) for serving as potential markers of NDDs by comparing levels of wastewater-borne BMAA and AMPA with regional U.S. rates of NDD prevalence. Newly developed liquid chromatography tandem mass spectrometry (LC-MS/MS) methods were applied to U.S. wastewater samples (n = 87) and resultant concentrations of putative biomarkers were statistically compared to NDD prevalence rates in conjunction with environmental data on algal blooms and agricultural glyphosate use. Locations of algal blooms were found to be significantly associated (p = 0.01) with ALS prevalence rates per 100,000 people. BMAA levels in wastewater were highly correlated (p < 0.0001) with ALS prevalence rates by region. BMAA in wastewater typically peaked in summer months. We conclude that NDD biomarker detection in wastewater holds potential value, with BMAA outperforming AMPA. Furthermore, prevalence data for NDDs may have to be reported to the Centers for Disease Control and Prevention at a higher geospatial resolution to further enhance the value for the present type of analysis. Further method development is needed for AMPA to be quantified using LC-MS/MS. Future method developments focusing on metabolites (e.g., AMPA) may enable epidemiologists to determine human exposure levels rather than the mere occurrence of toxic organic chemicals in the environment.}, } @article {pmid40056503, year = {2025}, author = {Zhan, A and Zhong, K and Zhang, K}, title = {Novel subcellular regulatory mechanisms of protein homeostasis and its implications in amyotrophic lateral sclerosis.}, journal = {Biochemical and biophysical research communications}, volume = {756}, number = {}, pages = {151582}, doi = {10.1016/j.bbrc.2025.151582}, pmid = {40056503}, issn = {1090-2104}, mesh = {*Amyotrophic Lateral Sclerosis/metabolism/pathology ; Humans ; *Proteostasis ; Animals ; Homeostasis ; Mitochondria/metabolism ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron degenerative disorder. Protein aggregates induce various forms of neuronal dysfunction and represent pathological hallmarks in ALS patients. Reducing protein aggregates could be a promising therapeutic strategy for ALS. While most studies have focused on cytoplasmic protein homeostasis, neurons adaptively reduce aggregates across subcellular compartments during stress through previously uncharacterized mechanisms. Here, we summarize novel compartment-specific proteostatic mechanisms: (1) the ERAD/RESET pathways, (2) HSPs-mediated nuclear sequestration, (3) mitochondrial aggregate import (MAGIC), (4) neurite-localized UPS/autophagosome and NMP, and (5) exopher-mediated extracellular disposal. These mechanisms collectively ensure cellular stress adaptation and provide novel therapeutic targets for ALS treatment.}, } @article {pmid40056413, year = {2025}, author = {Kahn, OI and Dominguez, SL and Glock, C and Hayne, M and Vito, S and Sengupta Ghosh, A and Adrian, M and Burgess, BL and Meilandt, WJ and Friedman, BA and Hoogenraad, CC}, title = {Secreted neurofilament light chain after neuronal damage induces myeloid cell activation and neuroinflammation.}, journal = {Cell reports}, volume = {44}, number = {3}, pages = {115382}, doi = {10.1016/j.celrep.2025.115382}, pmid = {40056413}, issn = {2211-1247}, mesh = {Animals ; *Neurons/metabolism/pathology ; *Neurofilament Proteins/metabolism/genetics ; Mice ; *Myeloid Cells/metabolism/pathology ; Microglia/metabolism/pathology ; Mice, Knockout ; Amyotrophic Lateral Sclerosis/pathology/metabolism ; *Neuroinflammatory Diseases/pathology/metabolism ; Mice, Inbred C57BL ; Disease Models, Animal ; Humans ; Calpain/metabolism ; Superoxide Dismutase-1/metabolism ; }, abstract = {Neurofilament light chain (NfL) is a neuron-specific cytoskeletal protein that provides structural support for axons and is released into the extracellular space following neuronal injury. While NfL has been extensively studied as a disease biomarker, the underlying release mechanisms and role in neurodegeneration remain poorly understood. Here, we find that neurons secrete low baseline levels of NfL, while neuronal damage triggers calpain-driven proteolysis and release of fragmented NfL. Secreted NfL activates microglial cells, which can be blocked with anti-NfL antibodies. We utilize in vivo single-cell RNA sequencing to profile brain cells after injection of recombinant NfL into the mouse hippocampus and find robust macrophage and microglial responses. Consistently, NfL knockout mice ameliorate microgliosis and delay symptom onset in the SOD1 mouse model of amyotrophic lateral sclerosis (ALS). Our results show that released NfL can activate myeloid cells in the brain and is, thus, a potential therapeutic target for neurodegenerative diseases.}, } @article {pmid40056296, year = {2025}, author = {Li, Z and Fan, J and Gong, Z and Tang, J and Yang, Y and Liu, M and Zhang, M}, title = {Association between cardiac autonomic dysfunction, cognitive impairment, and survival in patients with amyotrophic lateral sclerosis.}, journal = {Clinical autonomic research : official journal of the Clinical Autonomic Research Society}, volume = {35}, number = {3}, pages = {465-476}, pmid = {40056296}, issn = {1619-1560}, support = {82271478//the National Natural Science Foundation of China/ ; 2024AOXIANG05//the Research and Innovation Team Project for Scientific Breakthroughs at Shanxi Bethune Hospital/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/mortality/physiopathology/complications/psychology ; Male ; Female ; Middle Aged ; *Cognitive Dysfunction/physiopathology/mortality ; Aged ; *Autonomic Nervous System Diseases/physiopathology/mortality ; Heart Rate/physiology ; Electrocardiography, Ambulatory ; Adult ; }, abstract = {PURPOSE: The aim of this study was to investigate the relationship between cardiac autonomic dysfunction, cognitive impairment, and survival in patients with amyotrophic lateral sclerosis (ALS).

METHODS: The heart activity of 65 patients with ALS (28 with normal cognition [ALS-CN]; 37 with impaired cognition [ALS-CI]) and 38 healthy controls (HCs) was measured by 24-h Holter monitoring. Heart rate (HR) measures and heart rate variability (HRV) parameters were compared between the three study groups and, additionally, correlated with five Edinburgh Cognitive and Behavioral ALS Screen (ECAS) domains in the ALS subgroups. Age, gender, and educational level were adjusted. Factors associated with cognitive status were assessed using logistic regression. Survival predictors in patients with ALS were analyzed using the Kaplan-Meier estimator and Cox regression.

RESULTS: Compared to the HCs, patients with ALS-CI exhibited lower RRI (R-R-interval; P = 0.017), SDNN (standard deviation of all normal RR intervals; P = 0.013), SDNN Index (P = 0.044), and VLF power (very low-frequency power; P = 0.012). Total power was reduced in the ALS-CI group compared to the HCs (P = 0.036) and ALS-CN group (P = 0.048). In patients with ALS-CN, language negatively correlated with mean HR (P = 0.001) and positively with the RRI (P = 0.003), SDNN (P = 0.001), SDANN (standard deviation of the average NN intervals; P = 0.005), total power (P = 0.006), VLF power (P = 0.011), and low-frequency power (P = 0.026). Visuospatial function correlated positively with the SDNN Index (P = 0.041). In patients with ALS-CI, executive function (P = 0.015) and ECAS total score (P = 0.009) negatively correlated with the RMSSD (square root of mean sum-of-squares of differences between adjacent NN intervals), while visuospatial function correlated positively with normalized LF value (LFnu; P = 0.049). No associations were observed between the other cognitive domains and any of the 14 HRV/HR measures in patients with either ALS-CI or ALS-CN. SDNN ≤ 100 ms was linked to cognitive impairment (P = 0.039) and also showed a borderline association (P = 0.066) with poorer survival, while cognitive impairment (P = 0.010) was significantly linked to worse outcomes.

CONCLUSIONS: Patients with ALS with cognitive impairment demonstrated reduced cardiac autonomic modulations and altered cognitive autonomic associations. Cognitive impairment was linked to reduced survival, with baseline SDNN ≤ 100 ms identified as a potential marker.}, } @article {pmid40056187, year = {2025}, author = {Wiesenfarth, M and Forouhideh-Wiesenfarth, Y and Elmas, Z and Parlak, Ö and Weiland, U and Herrmann, C and Schuster, J and Freischmidt, A and Müller, K and Siebert, R and Günther, K and Fröhlich, E and Knehr, A and Simak, T and Bachhuber, F and Regensburger, M and Petri, S and Klopstock, T and Reilich, P and Schöberl, F and Schumann, P and Körtvélyessy, P and Meyer, T and Ruf, WP and Witzel, S and Tumani, H and Brenner, D and Dorst, J and Ludolph, AC}, title = {Correction: Clinical characterization of common pathogenic variants of SOD1-ALS in Germany.}, journal = {Journal of neurology}, volume = {272}, number = {4}, pages = {259}, doi = {10.1007/s00415-025-12952-1}, pmid = {40056187}, issn = {1432-1459}, } @article {pmid40055545, year = {2025}, author = {Giblin, A and Cammack, AJ and Blomberg, N and Anoar, S and Mikheenko, A and Carcolé, M and Atilano, ML and Hull, A and Shen, D and Wei, X and Coneys, R and Zhou, L and Mohammed, Y and Olivier-Jimenez, D and Wang, LY and Kinghorn, KJ and Niccoli, T and Coyne, AN and van der Kant, R and Lashley, T and Giera, M and Partridge, L and Isaacs, AM}, title = {Author Correction: Neuronal polyunsaturated fatty acids are protective in ALS/FTD.}, journal = {Nature neuroscience}, volume = {28}, number = {4}, pages = {913}, doi = {10.1038/s41593-025-01926-1}, pmid = {40055545}, issn = {1546-1726}, } @article {pmid40054065, year = {2025}, author = {Tserennadmid, B and Nam, MK and Park, JH and Rhim, H and Kang, S}, title = {HAP/ClpP-mediated disaggregation and degradation of Mutant SOD1 aggregates: A potential therapeutic strategy for Amyotrophic lateral sclerosis (ALS).}, journal = {Biochemical and biophysical research communications}, volume = {756}, number = {}, pages = {151533}, doi = {10.1016/j.bbrc.2025.151533}, pmid = {40054065}, issn = {1090-2104}, mesh = {*Amyotrophic Lateral Sclerosis/metabolism/genetics/therapy ; *Superoxide Dismutase-1/metabolism/genetics/chemistry ; Humans ; Protein Aggregates ; Proteolysis ; *Heat-Shock Proteins/metabolism/genetics ; Mutation ; Fluorescence Resonance Energy Transfer ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease marked by the accumulation of misfolded Cu/Zn superoxide dismutase (SOD1) protein aggregates in motor neurons, leading to progressive motor dysfunction and ultimately death. While the molecular chaperone heat shock protein 104 (Hsp104) has been shown to reduce protein misfolding by disaggregating protein aggregates, fully degrading these disaggregated proteins remains a significant challenge. In this study, we have investigated the effects of Hsp104 and its hyperactive variant, HAP, in combination with caseinolytic protease P (CIpP), on the disaggregation and degradation of SOD1 aggregates. Using laser confocal microscopy, fluorescence loss in photobleaching (FLIP), and biomolecular fluorescence complementation (BiFC)-fluorescence resonance energy transfer (FRET) assays, we demonstrate that Hsp104 effectively disaggregates SOD1 aggregates across 14 different G93 mutants, classified based on the properties of substituted amino acids, thus restoring protein mobility. Notably, the HAP/CIpP system not only disaggregates ALS-associated SOD1[G93A] aggregates but also promotes their proteolytic degradation, as evidenced by a significant reduction in high-order oligomers observed through BiFC and FRET assays. This dual mechanism of action presents. the HAP/CIpP system holds significant therapeutic potential for ALS and other neurodegenerative diseases characterized by protein aggregates, as it enables both effective disaggregation and degradation of toxic protein aggregates, thereby maintaining protein homeostasis.}, } @article {pmid40053600, year = {2025}, author = {Nie, Y and Szebényi, K and Wenger, LMD and Lakatos, A and Chinnery, PF}, title = {Origin and cell type specificity of mitochondrial DNA mutations in C9ORF72 ALS-FTLD human brain organoids.}, journal = {Science advances}, volume = {11}, number = {10}, pages = {eadr0690}, pmid = {40053600}, issn = {2375-2548}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/pathology ; *C9orf72 Protein/genetics ; *DNA, Mitochondrial/genetics ; *Brain/metabolism/pathology ; *Mutation ; *Organoids/metabolism/pathology ; Induced Pluripotent Stem Cells/metabolism ; *Frontotemporal Lobar Degeneration/genetics/pathology ; Mitochondria/genetics ; Astrocytes/metabolism/pathology ; }, abstract = {Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) are primarily genetic in ~20% of patients. Mutations in C9ORF72 are the most frequent cause, but it is not understood why there is notable regional pathology. An increased burden of mitochondrial DNA (mtDNA) mutations in ALS-FTLD brains implicates mitochondrial mechanisms; however, it remains unclear how and when these mutations arise. To address this, we generated cerebral organoids derived from human-induced pluripotent stem cells (hiPSCs) of patients with ALS-FTLD harboring the C9ORF72 hexanucleotide repeat expansion alongside CRISPR-corrected isogenic and healthy controls. Here, we show a higher mtDNA single-nucleotide variant (mtSNV) burden in astroglia derived from C9ORF72-mutant organoids, with some de novo mtSNVs likely due to the C9ORF72 repeat and others evading selection to reach higher heteroplasmy levels. Thus, the functional consequences of the regional accumulation of mtSNVs in C9ORF72 ALS-FTLD brains are likely to manifest through astroglial mitochondrial dysfunction.}, } @article {pmid40053462, year = {2025}, author = {Fazzini, L and Martis, A and Pateri, MI and Maccabeo, A and Borghero, G and Puligheddu, M and Montisci, R and Marchetti, MF}, title = {Long-term outcomes and worse clinical course in Takotsubo syndrome patients with amyotrophic lateral sclerosis.}, journal = {Journal of cardiovascular medicine (Hagerstown, Md.)}, volume = {26}, number = {4}, pages = {184-190}, doi = {10.2459/JCM.0000000000001711}, pmid = {40053462}, issn = {1558-2035}, mesh = {Humans ; Female ; *Takotsubo Cardiomyopathy/mortality/therapy/diagnosis/epidemiology/physiopathology ; Aged ; Male ; Retrospective Studies ; *Amyotrophic Lateral Sclerosis/mortality/epidemiology/diagnosis/therapy ; Prevalence ; Middle Aged ; Time Factors ; Hospital Mortality ; Risk Factors ; Shock, Cardiogenic/therapy/mortality/epidemiology ; Aged, 80 and over ; Prognosis ; Risk Assessment ; }, abstract = {AIMS: Takotsubo syndrome (TTS) is usually triggered by either physical/psychological stressors or comorbidities, neurological among others. The prevalence of amyotrophic lateral sclerosis (ALS) among TTS and whether it has a worse clinical course is not known. We aim to describe ALS prevalence and its impact on clinical presentation, clinical course, and long-term mortality.

METHODS: We retrospectively screened the overall TTS population admitted and followed up at our institution between 2007 and 2020. Clinical, electrocardiographic, and echocardiographic data were collected. Kaplan-Meier method was applied for time-to-event analysis to assess the outcome of interest of all-cause death.

RESULTS: Eighty-five patients with TTS were included in our study. Overall, the mean age was 70 ± 12 years, 86% were females. Six patients (7% prevalence) were affected by ALS. At admission, patients with ALS were more likely to present left ventricular systolic dysfunction (P = 0.007). The clinical course of ALS patients was more likely complicated by cardiogenic shock (P = 0.003) which required catecholamines infusion (P = 0.001) and mechanical ventilation (P = 0.009). Despite similar in-hospital mortality rates, ALS patients exhibited significantly elevated all-cause mortality during a median 6-year follow-up (hazard ratio, 19.189, 95% confidence interval 5.639-65.296, log-rank test P < 0.001) with significantly shorter hospitalization to death time (P = 0.039).

CONCLUSIONS: Our findings highlight a notable prevalence of ALS among TTS patients, with worse clinical presentation and in-hospital course in ALS-affected individuals. While in-hospital mortality rates were comparable, highlighting the reversible nature of TTS in both groups, long-term follow-up revealed significantly heightened all-cause mortality in ALS patients, emphasizing the impact of ALS on patient prognosis.}, } @article {pmid40051750, year = {2025}, author = {Dib, A and Salem, J and Fares, M}, title = {Recurrent Spontaneous Pneumothorax in the Setting of Amyotrophic Lateral Sclerosis.}, journal = {European journal of case reports in internal medicine}, volume = {12}, number = {3}, pages = {005151}, pmid = {40051750}, issn = {2284-2594}, abstract = {UNLABELLED: Spontaneous pneumothorax (SP) occurrence in amyotrophic lateral sclerosis (ALS) patients is relatively rare and may thus be under-recognised. This latter is a progressive neurodegenerative disorder, leading to muscle weakness and such respiratory complications. This article reports a case manifesting such a rare association.

LEARNING POINTS: The presence of spontaneous pneumothorax in amyotrophic lateral sclerosis patients can exacerbate respiratory insufficiency, leading to acute respiratory failure.Given the under-recognition of this latter complication, clinicians should maintain a high index of suspicion, especially in patients with amyotrophic lateral sclerosis presenting with sudden onset of dyspnoea or chest pain.Early detection and appropriate management are crucial to prevent further respiratory compromise.}, } @article {pmid40051509, year = {2025}, author = {Syed, SA and Singh, J and Elkholy, H and Rojnić Palavra, I and Tomicevic, M and Eric, AP and Pinto da Costa, M and Guloksuz, S and Radhakrishnan, R}, title = {International perspectives on physician knowledge, attitudes, and practices related to medical cannabis.}, journal = {Frontiers in public health}, volume = {13}, number = {}, pages = {1463871}, pmid = {40051509}, issn = {2296-2565}, support = {UL1 TR001863/TR/NCATS NIH HHS/United States ; }, mesh = {Humans ; *Medical Marijuana/therapeutic use ; Cross-Sectional Studies ; Female ; Male ; Adult ; *Health Knowledge, Attitudes, Practice ; *Physicians/psychology/statistics & numerical data ; Surveys and Questionnaires ; Middle Aged ; *Attitude of Health Personnel ; *Practice Patterns, Physicians'/statistics & numerical data ; *Internationality ; }, abstract = {BACKGROUND: The trends of recreational use of cannabis and the use of cannabis for medical indications (i.e., "medical cannabis") have grown in recent years. Despite that, there is still limited scientific evidence to guide clinical decision-making, and the strength of evidence for the medical use of cannabis is currently considered to be low. In contrast, there is growing evidence of negative health outcomes related to the use of cannabis. In this rapidly shifting landscape, the role of physician attitudes regarding the therapeutic value of cannabis has become essential. This study aimed to characterize knowledge/experience, attitudes, and potential predictors of clinical practice regarding medical cannabis.

METHODS: We conducted a cross-sectional survey of physicians from 17 countries between 2016 and 2018. The survey consisted of questions designed to explore physician knowledge, attitude, and practices regarding the use of medical cannabis. Descriptive statistics were used to examine willingness to recommend medical cannabis for medical and psychiatric indications, followed by regression analysis to identify the predictors of physician willingness to recommend medical cannabis.

RESULTS: A total of 323 physicians responded to the survey, among which 53% were women. The mean age was 35.4 ± 9.5 years, with 10.04 ± 8.6 years of clinical experience. Clinical experience with medical cannabis was overall limited (51.4% noted never having recommended medical cannabis and 33% noted inadequate knowledge regarding medical cannabis). The majority of respondents (84%) recognized the risk of psychosis with cannabis use, while only 23% correctly identified the risk of addiction with daily cannabis use. Overall, willingness to recommend medical cannabis was the highest for chemotherapy-induced nausea (67%), refractory chronic neuropathic pain (52%), and spasticity in amyotrophic lateral sclerosis (ALS; 51%).

CONCLUSION: This international study examining physician knowledge, attitudes, and practices related to medical cannabis revealed that there are significant gaps in domain-specific knowledge related to medical cannabis. There is a wide variability in willingness to recommend medical cannabis, which is not consistent with the current strength of evidence. This study thus highlights the need for greater education related to domain-specific knowledge about medical cannabis.}, } @article {pmid40050936, year = {2025}, author = {Jeejan, J and Rao, L and Sadasivan, S and Lopes, R and Dsouza, N}, title = {Impact of cysteine mutations on the structural dynamics and functional impairment of SOD1: insights into the pathogenicity of amyotrophic lateral sclerosis.}, journal = {Genomics & informatics}, volume = {23}, number = {1}, pages = {7}, pmid = {40050936}, issn = {1598-866X}, abstract = {Amyotrophic lateral sclerosis (ALS) is a rare neurodegenerative disease prevalent in American and European populations, with its onset and progression significantly influenced by mutations in the superoxide dismutase 1 (SOD1) protein. While previous studies have highlighted the effects of mutations in the metal-binding region and catalytic region and dimerisation of SOD1, the impact of mutations involving the Cysteine residue at the N-terminal end remains unexplored. This study investigates the effects of Cysteine-to-Trp, Phe, Ser, and Gly mutations at the 6th position of SOD1's N-terminal end on its structural dynamics and functional impairment. Our computational analysis using PolyPhen-2, PROVEAN, Meta-SNP, and PhD-SNP predicted mutations to be deleterious, with their negative impacts likely contributing to disease development. Furthermore, stability studies and bonding pattern changes due to the mutations, analysed by mCSM, SDM, DUET, Dynamut2, and PremPS revealed changes in free energy and disruption in intramolecular interactions. The molecular dynamics studies revealed distinct changes in stability patterns among the mutations, particularly in Cys6Trp and Cys6Phe. All the mutations primarily altered the catalytic region of the protein; additionally, Cys6Phe and Cys6Gly caused disruption in the metal-binding region. The impact of mutations on the dimerisation of SOD1, analysed using MM/PBSA showed destabilisation due to Cys6Phe mutation. These findings provide molecular insights into the clinical symptoms observed in patients, highlighting the critical impact of the Cys6Phe mutation on the metal-binding and catalytic loops of SOD1 along with destabilisation of dimer formation. Overall, our analysis offers valuable insights into the molecular mechanisms driving structural changes in SOD1 due to mutations, contributing to a deeper understanding of their role in ALS pathogenicity.}, } @article {pmid40050651, year = {2025}, author = {Gregorio-Sanz, MÁ and Marzo-Campos, JC and Segura-Heras, JV}, title = {Effects of nursing music intervention on cardiovascular patients transferred in advanced life support ambulances.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {7919}, pmid = {40050651}, issn = {2045-2322}, support = {PROMETEO/2021/063//Generalitat Valenciana/ ; }, mesh = {Humans ; Male ; Female ; *Music Therapy/methods ; *Ambulances ; Middle Aged ; Aged ; *Cardiovascular Diseases/therapy/nursing ; *Advanced Cardiac Life Support ; Case-Control Studies ; Blood Pressure ; }, abstract = {Patients with acute cardiovascular disease require out-of-hospital care during the most critical and vulnerable periods of their illness. This study aims to evaluate the influence of musical intervention in patients with acute cardiovascular disease during transfer in Advanced Life Support (ALS) ambulances using an analytical randomized controlled case-control experimental study conducted according to CONSORT guidelines. Forty-one subjects took part in the study. The patients required the administration of nitrates/antiarrhythmics (n = 11, 26.8%), (n = 5, 12.2%) antiemetics, and (n = 7, 17.1%) opioids. Statistically significant differences were found for blood pressure and the variable cardiovascular drugs between groups. The use of music therapy to complement other health measures in ALS ambulances lowers blood pressure values and reduces the need to administrate cardiovascular drugs, thus avoiding their possible side effects. It is easy to implement, has a low cost and should be monitored and controlled as a specific nursing intervention, included in the care of patients transferred by ambulances on a routine basis.}, } @article {pmid40050016, year = {2025}, author = {Martin, J and Johnson, R and Yemane, L and Unaka, N and Ebo, C and Hippolyte, J and Jones, M and Quinn, M and Barber, A and Floyd, B and Blankenburg, R and Hilgenberg, SL}, title = {Multi-institutional exploration of pediatric residents' perspectives on anti-racism curricula: a qualitative study.}, journal = {Medical education online}, volume = {30}, number = {1}, pages = {2474134}, pmid = {40050016}, issn = {1087-2981}, mesh = {Humans ; *Internship and Residency/organization & administration ; Qualitative Research ; Focus Groups ; *Curriculum ; *Pediatrics/education ; *Racism/prevention & control ; United States ; Female ; Male ; *Attitude of Health Personnel ; Adult ; Antiracism ; }, abstract = {BACKGROUND: Anti-racism curricula are increasingly being recognized as an integral component of medical education. To our knowledge, there has not yet been a publication exploring resident perspectives from multiple institutions and explicitly representing both underrepresented in medicine (UIM) and non-UIM perspectives.

OBJECTIVE: To explore and compare UIM and non-UIM pediatric residents' perspectives on the content and qualities of meaningful anti-racism curricula.

METHODS: We performed an IRB-approved multi-institutional, qualitative study that incorporated Sotto-Santiago et al's conceptual framework for anti-racism education. Between February and May 2021, we conducted focus groups of UIM and non-UIM pediatric residents at three large residency programs in the United States. We developed focus group guides using literature review, expert consensus, feedback from study team racial equity experts, and piloting. Focus groups were conducted virtually, audio-recorded, and transcribed verbatim. We employed thematic analysis to code transcripts, create categories, and develop themes until we reached thematic sufficiency. We completed member checking to ensure trustworthiness of themes.

RESULTS: Forty residents participated (19 UIM and 21 non-UIM) in a total of six focus groups. We identified 7 themes, summarized as: 1) racism in medicine is pervasive, therefore (2) anti-racism education is critical to the development of competent physicians, and 3) education should extend to all healthcare providers. 4) Residents desired education focused on action-oriented strategies to advance anti-racism, 5) taught by those with both learned and lived experiences with racism, 6) in a psychologically safe space for UIM residents, and 7) with adequate time and financial resources for successful implementation and engagement.

CONCLUSION: Our multi-institutional study affirms the need for pediatric resident anti-racism education, promotes co-creation as a method to affect culture change, and provides practical strategies for curricular design and implementation.}, } @article {pmid40050010, year = {2025}, author = {Sun, J and De Vocht, J and Stam, D and Lien, CH and Huang, YA and Lamaire, N and Laroy, M and Vansteelandt, K and D'Hondt, A and Van Den Bossche, MJA and Vandenberghe, R and Peeters, RR and Sunaert, S and van Damme, P and Vandenbulcke, M and Van den Stock, J}, title = {Neural correlates of memory deficits in premanifest C9orf72-repeat expansions.}, journal = {Journal of neurology, neurosurgery, and psychiatry}, volume = {96}, number = {9}, pages = {861-869}, doi = {10.1136/jnnp-2024-335169}, pmid = {40050010}, issn = {1468-330X}, abstract = {BACKGROUND: The premanifest stage in carriers of hexanucleotide repeat expansions in the C9orf72 gene (C9RE) is associated with memory impairment. The present study examines whether the impairment is general across domains or disproportionately affects specific stimulus categories such as socioemotional events, and its underlying functional neuroanatomy.

METHODS: This task-based fMRI-study included 21 premanifest C9RE (preC9RE) carriers and 24 controls. Participants encoded stimuli of (emotional and neutral) faces and houses, followed by a recognition task. Using univariate and multivoxel pattern analyses at whole-brain level and region-of-interest level, we investigated the neural change during encoding and retrieval processes, as well as the neural pattern similarity between encoding and retrieval.

RESULTS: Compared with controls, the preC9RE group demonstrated poorer performance in memorising faces (U=104, p=0.002), while their ability to memorise houses remained intact. The preC9RE group exhibited distinct neural patterns in the anterior insula during face encoding compared with the controls (accuracy>0.765, p<0.05). During face retrieval, the preC9RE group showed an increased neural response to encoded faces versus new faces in the right anterior insula (U=394, p=0.015). Individuals with preC9RE exhibited reduced encoding-retrieval neural similarity in the salience network specifically related to face stimuli (U=120, p=0.023).

CONCLUSIONS: The findings reveal functional changes in the salience network related to impaired social memory at the premanifest stage of C9RE. The findings further underscore the high potential of multidimensional neural response patterns as a sensitive biomarker for neurodegenerative functional changes, and the salience network as biomarker for C9RE disease staging.}, } @article {pmid40049531, year = {2025}, author = {Zhang, N and Dong, X}, title = {Causal relationship between gut microbiota, lipids, and neuropsychiatric disorders: A Mendelian randomization mediation study.}, journal = {Journal of affective disorders}, volume = {379}, number = {}, pages = {19-35}, doi = {10.1016/j.jad.2025.02.091}, pmid = {40049531}, issn = {1573-2517}, mesh = {Humans ; *Gastrointestinal Microbiome/genetics/physiology ; Mendelian Randomization Analysis ; *Mental Disorders/genetics/microbiology ; *Lipids/blood ; Genome-Wide Association Study ; Mediation Analysis ; }, abstract = {BACKGROUND: Numerous studies have shown an interconnection between the gut microbiota and the brain via the "gut-brain" axis. However, the causal relationships between gut microbiota, lipids, and neuropsychiatric disorders remain unclear. This study aimed to analyze potential associations among gut microbiota, lipids, and neuropsychiatric disorders-including AD, PD, ALS, MS, SCZ, MDD, and BD-using summary data from large-scale GWAS.

METHODS: Bidirectional Mendelian randomization (MR) with inverse variance weighting (IVW) was the primary method. Supplementary analyses included sensitivity analyses, Steiger tests, and Bayesian weighted MR (BWMR). Mediation analyses used two-step MR (TSMR) and multivariable MR (MVMR).

RESULTS: The analyses revealed 51 positive correlations (risk factors) (β > 0, P < 0.05) and 47 negative correlations (protective factors) (β < 0, P < 0.05) between gut microbiota and neuropsychiatric disorders. In addition, 35 positive correlations (β > 0, P < 0.05) and 22 negative correlations (β < 0, P < 0.05) between lipids and neuropsychiatric disorders were observed. Assessment of reverse causality with the seven neuropsychiatric disorders as exposures and the identified gut microbiota and lipids as outcomes revealed no evidence of reverse causality (P > 0.05). Mediation analysis indicated that the effect of the species Bacteroides plebeius on MDD is partially mediated through the regulation of phosphatidylcholine (16:0_20:4) levels (mediation proportion = 10.9 % [95 % CI = 0.0110-0.2073]).

CONCLUSION: This study provides evidence of a causal relationship between gut microbiota and neuropsychiatric disorders, suggesting lipids as mediators. These findings offer new insights into the mechanisms by which gut microbiota may influence neuropsychiatric disorders.}, } @article {pmid40049292, year = {2025}, author = {Faure-de Baets, J and Besnard, J and Banville, F and Cassereau, J and Allain, P}, title = {Effects of virtual reality mindfulness on cognition and well-being in ALS: A randomized trial protocol.}, journal = {Contemporary clinical trials}, volume = {152}, number = {}, pages = {107876}, doi = {10.1016/j.cct.2025.107876}, pmid = {40049292}, issn = {1559-2030}, mesh = {Humans ; *Mindfulness/methods ; *Quality of Life ; *Amyotrophic Lateral Sclerosis/psychology/therapy ; *Virtual Reality ; Randomized Controlled Trials as Topic ; Anxiety/therapy ; Depression/therapy ; *Cognitive Dysfunction/therapy/etiology ; Cognition ; Female ; Male ; Middle Aged ; Adult ; }, abstract = {Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease primarily affecting motor neurons but also leading to significant non-motor symptoms, including cognitive impairments, anxiety, depression, and behavioral changes, which severely impact quality of life. While mindfulness-based interventions (MBIs) have shown promise in alleviating psychological distress, their accessibility is often limited due to patients' physical impairments. Virtual reality (VR) could enhance engagement and immersion, offering a novel, more inclusive therapeutic approach. This randomized controlled trial (RCT) aims to evaluate the efficacy of a VR-based MBI compared to traditional mindfulness for ALS patients. Forty-six participants will be randomly assigned to an eight-week mindfulness program delivered either via VR or in a conventional format. The primary outcome is quality of life, assessed using the ALS-Specific Quality of Life Scale (ALSSQOL-R). Secondary outcomes include cognitive function, anxiety, depression, behavioral changes, and mindfulness propensity, evaluated at baseline, post-intervention, and three-month follow-up. The study will also examine VR usability and potential accessibility challenges for ALS patients. By addressing a critical gap in non-pharmacological psychological care, this study will provide key insights into the feasibility and benefits of VR-based MBIs. If effective, VR mindfulness could offer an innovative, scalable solution to improve emotional well-being and quality of life in ALS, making psychological support more accessible for patients with severe physical limitations.}, } @article {pmid40049153, year = {2025}, author = {Cho, HW and Jung, S and Park, KH and Choi, JW and Heo, JS and Kim, J and Yun, H and Yu, D and Son, J and Choi, BM}, title = {Deep-Learning-Based Multi-Class Classification for Neonatal Respiratory Diseases on Chest Radiographs in Neonatal Intensive Care Units.}, journal = {Neonatology}, volume = {122}, number = {4}, pages = {446-454}, doi = {10.1159/000545107}, pmid = {40049153}, issn = {1661-7819}, mesh = {Humans ; Infant, Newborn ; *Deep Learning ; Intensive Care Units, Neonatal ; Retrospective Studies ; *Radiography, Thoracic ; Female ; Male ; Algorithms ; Republic of Korea ; Respiratory Distress Syndrome, Newborn/diagnostic imaging/classification ; Lung/diagnostic imaging ; *Respiratory Tract Diseases/diagnostic imaging/classification ; }, abstract = {INTRODUCTION: Accurate and timely interpretation of chest radiographs is essential for assessing respiratory distress and guiding clinical management to improve outcomes of critically ill newborns. This study aimed to introduce a deep-learning-based automated algorithm designed to classify various neonatal respiratory diseases and healthy lungs using a large dataset of high-quality, multi-class labeled chest X-ray images from neonatal intensive care units.

METHODS: Portable supine chest X-ray images for six common conditions (healthy lung, respiratory distress syndrome [RDS], transient tachypnea of the newborn [TTN], air leak syndrome [ALS], atelectasis, and bronchopulmonary dysplasia [BPD]) and demographic variables (gestational age and birth weight) were retrospectively collected from 10 university hospitals in Korea. Ground truth for manual classification of these conditions was generated by 20 neonatologists and validated by others from different hospitals. The dataset, consisting 34,598 for training, 4,370 for validation, and 4,370 for testing, was used to train a modified ResNet50-based deep-learning model for automatic classification.

RESULTS: The automatic classification algorithm showed high concordance with human-annotated classifications, achieving an overall testing accuracy of 83.96% and an F1 score of 83.68%. The F1 score for each condition was 87.38% for "healthy lung" and 92.19% for "BPD," 90.65% for "ALS," 90.30% for "RDS," 86.56% for "atelectasis," and 70.84% for "TTN."

CONCLUSION: We introduced a deep-learning-based automated algorithm to classify neonatal respiratory diseases using a large dataset of high-quality, multi-class labeled chest X-ray images, incorporating non-imaging data, which could support neonatologists in making timely and accurate decisions for critically ill newborns.}, } @article {pmid40048825, year = {2025}, author = {Kacker, K and Chetty, N and Feldman, AK and Bennett, J and Yoo, PE and Fry, A and Lacomis, D and Harel, NY and Nogueira, RG and Majidi, S and Opie, NL and Collinger, JL and Oxley, TJ and Putrino, DF and Weber, DJ}, title = {Motor activity in gamma and high gamma bands recorded with a Stentrode from the human motor cortex in two people with ALS.}, journal = {Journal of neural engineering}, volume = {22}, number = {2}, pages = {}, pmid = {40048825}, issn = {1741-2552}, support = {UH3 NS120191/NS/NINDS NIH HHS/United States ; }, mesh = {Female ; Humans ; Male ; Middle Aged ; *Amyotrophic Lateral Sclerosis/physiopathology/diagnosis ; *Brain-Computer Interfaces ; *Electrocorticography/methods/instrumentation ; Electrodes, Implanted ; *Gamma Rhythm/physiology ; *Motor Activity/physiology ; *Motor Cortex/physiopathology/physiology ; Movement/physiology ; *Stents ; Clinical Trials as Topic ; }, abstract = {Objective.This study examined the strength and stability of motor signals in low gamma and high gamma bands of vascular electrocorticograms (vECoG) recorded with endovascular stent-electrode arrays (Stentrodes) implanted in the superior sagittal sinus of two participants with severe paralysis due to amyotrophic lateral sclerosis.Approach.vECoG signals were recorded from two participants in the COMMAND trial, an Early Feasibility Study of the Stentrode brain-computer interface (BCI) (NCT05035823). The participants performed attempted movements of their ankles or hands. The signals were band-pass filtered to isolate low gamma (30-70 Hz) and high gamma (70-200 Hz) components. The strength of vECoG motor activity was measured as signal-to-noise ratio (SNR) and the percentage change in signal amplitude between the rest and attempted movement epochs, which we termed depth of modulation (DoM). We trained and tested classifiers to evaluate the accuracy and stability of detecting motor intent.Main results.Both low gamma and high gamma were modulated during attempted movements. For Participant 1, the average DoM across channels and sessions was 125.41 ± 17.53% for low gamma and 54.23 ± 4.52% for high gamma, with corresponding SNR values of 6.75 ± 0.37 dB and 3.69 ± 0.28 dB. For Participant 2, the average DoM was 22.77 ± 4.09% for low gamma and 22.53 ± 2.04% for high gamma, with corresponding SNR values of 1.72 ± 0.25 dB and 1.73 ± 0.13 dB. vECoG amplitudes remained significantly different between rest and move periods over the 3 month testing period, with >90% accuracy in discriminating attempted movement from rest epochs for both participants. For Participant 1, the average DoM was strongest during attempted movements of both ankles, while for Participant 2, the DoM was greatest for attempted movement of the right hand. The overall classification accuracy was 91.43% for Participant 1 and 70.37% for Participant 2 in offline decoding of multiple attempted movements and rest conditions.Significance.By eliminating the need for open brain surgery, the Stentrode offers a promising BCI alternative, potentially enhancing access to BCIs for individuals with severe motor impairments. This study provides preliminary evidence that the Stentrode can detect discriminable signals indicating motor intent, with motor signal modulation observed over the 3 month testing period reported here.}, } @article {pmid40048117, year = {2025}, author = {Kwon, S and Kim, B and Han, KD and Jung, W and Cho, EB and Shin, DW and Min, JH}, title = {Increased risk of ischemic stroke in amyotrophic lateral sclerosis: a nationwide cohort study in South Korea.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {46}, number = {6}, pages = {2687-2695}, pmid = {40048117}, issn = {1590-3478}, support = {HI20C1073//Ministry of Health and Welfare/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/epidemiology/complications ; Male ; Republic of Korea/epidemiology ; Female ; Middle Aged ; Aged ; *Ischemic Stroke/epidemiology ; Cohort Studies ; Risk Factors ; }, abstract = {BACKGROUND: We investigated the risk of ischemic stroke in ALS and analyzed the effect of ALS-related physical disability using the Korean National Health Insurance Service database.

METHODS: A total of 2,251 ALS patients diagnosed between January 1, 2012, and December 31, 2015, and 1:10 age- and sex-matched control populations were included. Cases that participated in the national health check-up programs were selected. A Cox hazard regression model was used to examine the hazard ratios (HRs) for ischemic stroke in ALS after adjusting for potential confounders.

RESULTS: A total of 681 ALS patients and 10,934 non-ALS participants were selected. ALS patients were slightly younger than the control group (60.3 ± 10.1 years vs. 61.0 ± 10.5 years, p = 0.105), and the proportion of male patients was similar between the two groups (61.6% vs. 60.9%, p = 0.722). ALS patients were more likely to have a lower body mass index (23.1 ± 2.92 vs. 24.0 ± 3.1, p < 0.001) and obstructive sleep apnea syndrome (0.59% vs. 0.06%, p < 0.001) than the controls. In ALS patients, the incidence rate of ischemic stroke was 6.32 per 1,000 person-years, and the adjusted HR of ischemic stroke was 2.58 (95% confidence interval 1.38 - 4.82) compared with the matched group. The risk of ischemic stroke did not differ by the presence of disability in ALS patients.

CONCLUSIONS: Our findings suggest that ALS patients have an increased risk of ischemic stroke compared with controls, but the risk did not differ by the presence of disability in ALS.}, } @article {pmid40047927, year = {2025}, author = {Ludolph, A and Klose, V and Dreyhaupt, J and Del Tredici, K and Braak, H}, title = {The deltoid muscle and the pattern of paresis in ALS.}, journal = {Journal of neurology}, volume = {272}, number = {3}, pages = {253}, pmid = {40047927}, issn = {1432-1459}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/complications/physiopathology/pathology ; *Deltoid Muscle/physiopathology/pathology ; Male ; Female ; Middle Aged ; Aged ; *Paresis/etiology/physiopathology/pathology ; Adult ; *Muscle, Skeletal/physiopathology ; Aged, 80 and over ; Pyramidal Tracts/physiopathology ; Prospective Studies ; }, abstract = {There is neuroanatomical and clinical evidence that the corticospinal tract governs the patterns of pareses in sporadic ALS. These patterns are mirrored by phylogenetically young monosynaptic corticomotor neuronal connections. It is well known that, clinically, dysfunction of the deltoid muscle contributes considerably to the early disability of the ALS patient. In this study, we prospectively compared the degree of pareses of the deltoid muscle with the triceps and biceps brachii in N = 71 patients (426 muscles). We could show that the extent of involvement of the deltoid muscle early in the disease process resembles that of the biceps rather than the triceps brachii. This pattern is consistent with functional data of the corticospinal monosynaptic connectivity of all three muscles.}, } @article {pmid40047382, year = {2025}, author = {Murray, D and Rooney, J and Meldrum, D and Al-Chalabi, A and Bunte, TM and Chiwera, T and Choudhury, M and Chio, A and Fenton, L and Fortune, J and Maidment, L and Manera, U and McDermott, CJ and Meyjes, M and Tattersall, R and Torrieri, MC and Van Damme, P and Vanderlinden, E and Wood, C and Van Den Berg, LH and Hardiman, O}, title = {Respiratory measurements, respiratory symptoms, and quality of life in ALS: results from the REVEALS study.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {26}, number = {5-6}, pages = {467-477}, doi = {10.1080/21678421.2025.2471421}, pmid = {40047382}, issn = {2167-9223}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/complications/physiopathology/psychology/epidemiology ; *Quality of Life/psychology ; Male ; Female ; Middle Aged ; Aged ; Longitudinal Studies ; Dyspnea/etiology/physiopathology ; Fatigue/etiology ; Respiratory Function Tests ; }, abstract = {Objective: Progressing respiratory weakness throughout the course of amyotrophic lateral sclerosis (ALS) is clinically associated with distressing symptoms, including dyspnea, orthopnea, and difficulty clearing secretions. Fatigue, poor sleep, and reduced quality of life are also considered to be associated with declining respiratory function. Respiratory measurements guide prescription of interventions, which aim to alleviate symptoms. The relationships between respiratory measurements and patient reported symptoms are currently unclear. Method: The REVEALS study was a longitudinal, observational, multisite study of decline in respiratory function in people with ALS attending six European centers. Respiratory measures (forced and slow vital capacity (F/SVC), sniff nasal inspiratory pressure (SNIP), and peak cough flow) were collected, as were the presence of respiratory symptoms and simple quality of life, fatigue and sleep measures. We used Bayesian's multivariate models to explore the associations of the respiratory measures with outcome variables. Results: Two hundred and eighty participants completed in-person assessments over a median of 8 (IQR 2.3, 14.1) months, with 974 data collection timepoints. The probability of reporting symptoms including dyspnea, orthopnea, and difficulty clearing secretions increased with decreasing respiratory measurement scores. The probability of reporting moderately low quality of life and moderate fatigue also increased with decreasing test scores, but reported sleep quality was not associated with respiratory scores. Conclusion: Respiratory weakness in people with ALS was associated with symptoms including dyspnea, orthopnea, and difficulty clearing secretions. The probability of reporting symptoms increased incrementally as respiratory weakness increased, supporting the use of both respiratory measurements and the presence of symptoms in making decisions about clinical interventions.}, } @article {pmid40046336, year = {2025}, author = {Öztürk, MM and Emgård, J and García-Revilla, J and Fernández-Calle, R and Yang, Y and Deierborg, T and Roos, TT}, title = {The role of microglia in the prion-like transmission of protein aggregates in neurodegeneration.}, journal = {Brain communications}, volume = {7}, number = {2}, pages = {fcaf087}, pmid = {40046336}, issn = {2632-1297}, abstract = {Numerous neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis share a neuropathological hallmark: aberrant protein aggregation in the CNS. Microglia, the brain's innate immune cells, also play a pivotal role in the pathogenesis of these disorders. Multiple studies indicate that these pathological aggregates can propagate throughout the brain in a prion-like manner. A protein/peptide that adopts a prion-like conformation can induce homologous proteins to misfold into a prion-like conformation through templated seeding, enabling cell-to-cell spread and accelerating protein aggregation throughout the brain. Two important questions in the prion-like paradigm are where the prion-like misfolding occurs and how the prion-like aggregates are spread throughout the CNS. Here, we review the role of microglia and associated inflammation in the prion-like spread of pathologically aggregated proteins/peptides in Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis. A growing body of evidence suggests that microglia can internalize prion-like proteins and transport them to neighbouring neurons and other glial cells. Microglia may also influence the potential seeding of proteins in neurons and induce inflammatory pathways in their microenvironment. This review aims to broaden the understanding of the role of microglia in the prion-like spread of protein aggregation.}, } @article {pmid40045432, year = {2025}, author = {Blair, K and Martinez-Serra, R and Gosset, P and Martín-Guerrero, SM and Mórotz, GM and Atherton, J and Mitchell, JC and Markovinovic, A and Miller, CCJ}, title = {Structural and functional studies of the VAPB-PTPIP51 ER-mitochondria tethering proteins in neurodegenerative diseases.}, journal = {Acta neuropathologica communications}, volume = {13}, number = {1}, pages = {49}, pmid = {40045432}, issn = {2051-5960}, support = {MR/X021858/1//UK Research and Innovation/ ; }, mesh = {Humans ; *Endoplasmic Reticulum/metabolism ; *Mitochondria/metabolism ; *Neurodegenerative Diseases/metabolism/pathology ; Animals ; *Mitochondrial Proteins/metabolism ; *Vesicular Transport Proteins/metabolism/chemistry ; Signal Transduction/physiology ; Protein Tyrosine Phosphatases ; }, abstract = {Signaling between the endoplasmic reticulum (ER) and mitochondria regulates many of the seemingly disparate physiological functions that are damaged in neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). A number of studies have now demonstrated that ER-mitochondria signaling is perturbed in these diseases and there is evidence that this may be a driving mechanism in disease onset and progression. VAPB and PTPIP51 are ER-mitochondria tethering proteins; VAPB is an ER protein and PTPIP51 is an outer mitochondrial membrane protein and the two proteins interact to enable inter-organelle signaling. The VAPB-PTPIP51 interaction is disrupted in Alzheimer's disease, Parkinson's disease, FTD and ALS. Here we review the roles of VAPB and PTPIP51 in ER-mitochondria signaling and the mechanisms by which neurodegenerative disease insults may disrupt the VAPB-PTPIP51 interaction.}, } @article {pmid40044663, year = {2025}, author = {Abu-Rumeileh, S and Scholle, L and Mensch, A and Großkopf, H and Ratti, A and Kölsch, A and Stoltenburg-Didinger, G and Conrad, J and De Gobbi, A and Barba, L and Steinacker, P and Klafki, HW and Oeckl, P and Halbgebauer, S and Stapf, C and Posa, A and Kendzierski, T and Silani, V and Hausner, L and Ticozzi, N and Froelich, L and Weishaupt, JH and Verde, F and Otto, M}, title = {Phosphorylated tau 181 and 217 are elevated in serum and muscle of patients with amyotrophic lateral sclerosis.}, journal = {Nature communications}, volume = {16}, number = {1}, pages = {2019}, pmid = {40044663}, issn = {2041-1723}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/blood/metabolism/pathology/diagnosis ; *tau Proteins/blood/metabolism ; Male ; Female ; Middle Aged ; Aged ; Phosphorylation ; Alzheimer Disease/blood/metabolism/diagnosis/pathology ; Biomarkers/blood/metabolism ; Adult ; *Muscle, Skeletal/metabolism/pathology ; Mass Spectrometry ; Case-Control Studies ; Aged, 80 and over ; Immunohistochemistry ; }, abstract = {Blood phosphorylated (p)-tau 181 and p-tau 217 have been proposed as accurate biomarkers of Alzheimer's disease (AD) pathology. However, blood p-tau 181 is also elevated in amyotrophic lateral sclerosis (ALS) without a clearly identified source. We measured serum p-tau 181 and p-tau 217 in a multicentre cohort of ALS (n = 152), AD (n = 111) cases and disease controls (n = 99) recruited from four different centres. Further, we investigated the existence of both p-tau species using immunohistochemistry (IHC) and mass spectrometry (MS) in muscle biopsies of ALS cases (IHC: n = 13, MS: n = 5) and disease controls (IHC: n = 14, MS: n = 5) from one cohort. Serum p-tau 181 and p-tau 217 were higher in AD and ALS patients compared to disease controls. IHC and MS analyses revealed the presence of p-tau 181 and 217 in muscle biopsies from both ALS cases and disease controls, with ALS samples showing increased p-tau reactivity in atrophic muscle fibres. Blood p-tau species could potentially be used to diagnose both ALS and AD.}, } @article {pmid40044193, year = {2025}, author = {Ross, WT and Buday, S and Yakel, E and Khabele, D and Balls-Berry, J and As-Sanie, S and Colditz, G and Baumann, AA}, title = {Does interdisciplinary group care for the treatment of endometriosis improve pain interference: protocol for a pilot randomised controlled trial at an urban academic medical centre.}, journal = {BMJ open}, volume = {15}, number = {3}, pages = {e097372}, pmid = {40044193}, issn = {2044-6055}, support = {K23 HD110710/HD/NICHD NIH HHS/United States ; KL2 TR002346/TR/NCATS NIH HHS/United States ; }, mesh = {Adult ; Female ; Humans ; Academic Medical Centers ; *Chronic Pain/therapy/etiology ; *Endometriosis/therapy/complications ; *Pain Management/methods ; Pain Measurement ; *Patient Care Team ; *Pelvic Pain/therapy/etiology ; Pilot Projects ; Quality of Life ; Randomized Controlled Trials as Topic ; }, abstract = {INTRODUCTION: Endometriosis affects 10-15% of people assigned female at birth and can cause chronic pelvic pain and impair many domains of quality of life, such as fertility, mood and bladder, bowel and sexual function. Current treatments often fail, leading to recurrent pain and the need for reintervention. As endometriosis negatively affects many domains of life, a variety of non-pharmacological treatments modestly improve symptoms. To bundle these interventions into accessible packaging, our interdisciplinary team developed a novel endometriosis intervention titled 'Peer-Empowered Endometriosis Pain Support (PEEPS)', an 8-week integrative group care intervention. Here, we present the protocol for a pilot randomised controlled trial (RCT) to evaluate the effectiveness and implementation of PEEPS for people with endometriosis-associated pain refractory to surgical management. We hypothesise that patients who complete the PEEPS programme will show a greater decrease in pain interference in daily activities at intervention completion as compared with baseline than those in the education arm.

METHODS AND ANALYSIS: This is a hybrid type 1 effectiveness-implementation mixed-methods RCT in which 60 participants will be randomised using computer-generated random numbers stratified by group in the ratio 1:1 to PEEPS plus usual versus educational handout plus usual care. The primary outcome is change in pain interference from baseline to intervention completion. Secondary outcomes include change in pain interference from baseline to 6 months and 12 months postintervention, as well as change in other quality-of-life measures as measured by nine validated questionnaires from baseline to completion, 6 months and 12 months. Proctor et al's Implementation Outcomes Framework will be used to evaluate acceptability, appropriateness and feasibility of PEEPS implementation, and the Consolidated Framework for Implementation Research will be used to guide the evaluation of barriers and facilitators of PEEPS at the patient and provider levels. Primary data analyses will follow the intention-to-treat principle. Descriptive statistics and two-sample t-tests for normally distributed values and Wilcoxon Rank-Sum test were performed for non-normally distributed values. Frequency analysis and Fisher's exact or χ[2] tests will be used for categoric variables as appropriate. Longitudinal analysis of the primary and secondary outcomes will be conducted with a mixed-effects model to investigate the effect of PEEPS compared with education. Least square means (LSMs) and the corresponding 95% CIs at each timepoint, as well as LSM differences and 95% CIs between any post-baseline and baseline will be provided for the outcomes. ORs and 95% CIs will be calculated for categorical outcomes. Qualitative data will be collected in the form of open-ended feedback, focus groups with programme completers and semistructured interviews with participants who complete two or fewer sessions. The analysis will use an embedded design-experimental model in which quantitative and qualitative outcomes will occur concurrently with weight priority given to quantitative data.

ETHICS AND DISSEMINATION: This trial was approved by the Washington University in St. Louis Institutional Review Board (protocol 202402082) on 27 March 2024 and has low risk of harm to participants. All deidentified data from this project will be shared via Digital Commons@Becker. The findings of this study will be disseminated via scientific meetings and peer-reviewed journals. The results and conclusions will be summarised for patients and the public in common language using infographics to make the findings accessible. This pilot RCT will yield the effect size for PEEPS and generate implementation context and outcomes data to guide PEEPS application to real-world practice. If PEEPS proves to be effective, this study will inform adaptation and scaling to improve the lives of people with endometriosis through a non-hormonal, fertility-preserving approach.

TRIAL REGISTRATION NUMBER: ClinicalTrials.gov; NCT06549985.}, } @article {pmid40042459, year = {2025}, author = {Lee, SM and Yoon, SJ and Park, KW and Kim, A and Kim, HJ and Jung, NY and Jang, H and Seeley, WW and Kim, YE and Moon, SY and Kim, EJ and , }, title = {Semantic variant primary progressive aphasia with ANXA11 p.D40G.}, journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association}, volume = {21}, number = {3}, pages = {e14566}, pmid = {40042459}, issn = {1552-5279}, support = {2021-ER1004-01//Korea National Institute of Health/ ; 2024-ER1001-00//Korea National Institute of Health/ ; RS-2024-00337993//Korea Dementia Research Project through the Korea Dementia Research Center, funded by the Ministry of Health & Welfare and Ministry of Science and ICT, Republic of Korea/ ; }, mesh = {Humans ; *Aphasia, Primary Progressive/genetics ; Male ; Female ; Aged ; Middle Aged ; *Annexins/genetics ; Republic of Korea ; *Frontotemporal Dementia/genetics ; Cohort Studies ; High-Throughput Nucleotide Sequencing ; DNA-Binding Proteins/genetics ; }, abstract = {INTRODUCTION: Pathogenic variants of annexin A11 (ANXA11) have been identified in patients with amyotrophic lateral sclerosis (ALS) with or without frontotemporal dementia (FTD). We explored ANXA11 pathogenic variants in a Korean FTD cohort to investigate the prevalence and the role of ANXA11 variation in FTD.

METHODS: We used next-generation sequencing (NGS) to search for pathogenic variants in ANXA11 in two nationwide FTD cohorts in Korea.

RESULTS: We identified a pathogenic variant in ANXA11, c.119A > G (p.D40G), in six patients with semantic variant primary progressive aphasia (svPPA), representing 5.5% of the svPPA cohort (6/109), and representing 2.3% of the FTD cohort overall (6/259). Only one patient later developed features suggestive of ALS.

DISCUSSION: This study links a rare variant in ANXA11 to a sporadic clinical syndrome in which specific TAR DNA-binding protein-43 (TDP-43) forms an obligate co-fibril with annexin A11. The variant, p.D40G, lies within the N-terminal portion of annexin A11's TDP-43 type C interacting domain, suggesting that genetic variation in that region may promote co-fibrillization.

HIGHLIGHTS: The pathogenic variant of annexin A11 (ANXA11I) is linked to frontotemporal dementia (FTD) syndrome. ANXA11 (p.D40G) may be one of the possible genetic causes of semantic variant primary progressive aphasia (svPPA). ANXA11 (p.D40G) may enhance heteromeric amyloid filaments of annexin A11 and TDP-43, promoting frontotemporal lobar degeneration with TAR DNA-binding protein-43 (TDP-43) inclusions (FTLD-TDP) type C.}, } @article {pmid40041912, year = {2025}, author = {Dash, UC and Bhol, NK and Swain, SK and Samal, RR and Nayak, PK and Raina, V and Panda, SK and Kerry, RG and Duttaroy, AK and Jena, AB}, title = {Oxidative stress and inflammation in the pathogenesis of neurological disorders: Mechanisms and implications.}, journal = {Acta pharmaceutica Sinica. B}, volume = {15}, number = {1}, pages = {15-34}, pmid = {40041912}, issn = {2211-3835}, abstract = {Neuroprotection is a proactive approach to safeguarding the nervous system, including the brain, spinal cord, and peripheral nerves, by preventing or limiting damage to nerve cells and other components. It primarily defends the central nervous system against injury from acute and progressive neurodegenerative disorders. Oxidative stress, an imbalance between the body's natural defense mechanisms and the generation of reactive oxygen species, is crucial in developing neurological disorders. Due to its high metabolic rate and oxygen consumption, the brain is particularly vulnerable to oxidative stress. Excessive ROS damages the essential biomolecules, leading to cellular malfunction and neurodegeneration. Several neurological disorders, including Alzheimer's, Parkinson's, Amyotrophic lateral sclerosis, multiple sclerosis, and ischemic stroke, are associated with oxidative stress. Understanding the impact of oxidative stress in these conditions is crucial for developing new treatment methods. Researchers are exploring using antioxidants and other molecules to mitigate oxidative stress, aiming to prevent or slow down the progression of brain diseases. By understanding the intricate interplay between oxidative stress and neurological disorders, scientists hope to pave the way for innovative therapeutic and preventive approaches, ultimately improving individuals' living standards.}, } @article {pmid40039939, year = {2024}, author = {Udhayakumar, R and Gopakumar, S and Rahman, S and Karmakar, C}, title = {Nonlinear Assessment of Gait Signal Complexity in Neurodegenerative Disorders.}, journal = {Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference}, volume = {2024}, number = {}, pages = {1-4}, doi = {10.1109/EMBC53108.2024.10781711}, pmid = {40039939}, issn = {2694-0604}, mesh = {Humans ; *Neurodegenerative Diseases/physiopathology/diagnosis ; Algorithms ; *Gait ; Nonlinear Dynamics ; Entropy ; *Signal Processing, Computer-Assisted ; }, abstract = {The human gait cycle undergoes discernible alterations upon the onset of neurodegenerative diseases (NDD) such as Parkinson's, Huntington's, and Amyotrophic lateral sclerosis. Each specific neurodegenerative disorder imparts a distinct influence on human gait dynamics, and precise quantification of these changes holds the potential for accurate methods of NDD detection.Nonlinear entropy algorithms, such as sample entropy (SampEn), find widespread use in physiological signal analysis. SampEn gauges signal complexity by identifying pattern matches within windowed sub-segments of the signal. However, traditional SampEn is notably dependent on user-defined parameters, particularly the tolerance parameter r, leading to inaccuracies in complexity information.SampEn profiling emerges as an alternative concept, eliminating the need for an input r parameter. This data-driven algorithm autonomously generates a set of 'r' values based on the signal's dynamics, yielding a comprehensive SampEn profile. The SampEn profile, containing extensive information about the signal's complexity, serves as a valuable resource for extracting secondary entropy features.In this study, we have contrasted the efficacy of traditional SampEn with SampEn profile-based secondary features such as Total SampEn (TSE) and Median SampEn (MSE), in identifying neurological states. Our findings consistently reveal that secondary features derived from the reduced-parametric SampEn profiling method outperform the traditional parametric SE in distinguishing control cohorts from specific Neurodegenerative Disease (NDD) cohorts.}, } @article {pmid40039399, year = {2024}, author = {Rechichi, I and Amprimo, G and Cicolin, A and Olmo, G}, title = {Predicting Amyotrophic Lateral Sclerosis Progression: an EMG-based Survival Analysis.}, journal = {Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference}, volume = {2024}, number = {}, pages = {1-4}, doi = {10.1109/EMBC53108.2024.10782485}, pmid = {40039399}, issn = {2694-0604}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology/diagnosis/mortality ; *Electromyography/methods ; Disease Progression ; Survival Analysis ; Male ; Female ; Middle Aged ; Aged ; Longitudinal Studies ; }, abstract = {Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disease, ultimately leading to muscle inefficiency and death. A vast majority of people with ALS also suffer from sleep disorders. Previous studies highlighted the presence of REM Sleep Without Atonia (RSWA) in an ALS cohort, and suggested its strong correlation with the disease severity. This study investigates the ability of electromyography (EMG) parameters recorded during Rapid-eye Movement (REM) sleep to predict disease progress and outcome rapidity in ALS. Survival models trained on a cohort of 45 ALS patients undergoing a longitudinal study, revealed a promising predictive power for the proposed EMG-derived metrics (c-index ≥ 0.65) and encouraging goodness of fit (through c-index and χ[2]). These results suggest the possibility of employing the trained model in follow-up procedures, based on non-invasive, lightweight EMG metrics, which would significantly ease disease monitoring and help personalized symptomatic care.}, } @article {pmid40039278, year = {2024}, author = {Murphy, EK and Doussan, A and Verga, S and Stommel, EW and McIlduff, C and Halter, RJ and Rutkove, SB}, title = {Assessing Pulmonary Function in ALS using Electrical Impedance Tomography.}, journal = {Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference}, volume = {2024}, number = {}, pages = {1-4}, doi = {10.1109/EMBC53108.2024.10781742}, pmid = {40039278}, issn = {2694-0604}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology/diagnosis ; Electric Impedance ; *Tomography/methods ; *Respiratory Function Tests/methods ; Male ; Female ; Middle Aged ; Algorithms ; Aged ; *Lung/physiopathology ; Case-Control Studies ; }, abstract = {This study aimed to determine an optimal model involving thoracic electrical impedance tomography (EIT) metrics and patient geometric information to best correlate to standard pulmonary function test (PFT) measures in a cohort of 32 ALS patients and 32 age-matched healthy controls. Thoracic EIT is a non-invasive technology in which an electrode belt chest allows for real-time impedance imaging of respiratory function. The optimal form of the model was determined via a genetic algorithm a novel technique for model generation in EIT applications. Combining multiple metrics yielded optimal r[2] values of 0.62 and 0.66 for 1- and 2-term regression models optimized. The results appear very promising and further refinement of the technology appears warranted.}, } @article {pmid40038221, year = {2025}, author = {Mustafa, F and Mittal, S and Garg, D and Agarwal, A and Garg, A and Gupta, BK and Soneja, M and Srivastava, AK}, title = {HIV associated motor neuron disease (MND): A case series with systematic review of literature.}, journal = {Journal of neurovirology}, volume = {31}, number = {1}, pages = {1-15}, pmid = {40038221}, issn = {1538-2443}, mesh = {Humans ; *HIV Infections/drug therapy/complications/virology ; Male ; Middle Aged ; *Amyotrophic Lateral Sclerosis/virology/drug therapy/diagnostic imaging/pathology ; Female ; Adult ; *Motor Neuron Disease/virology/drug therapy ; Viral Load ; CD4 Lymphocyte Count ; Anti-HIV Agents/therapeutic use ; }, abstract = {Human immunodeficiency virus (HIV) associated motor neuron disease (MND) is very rare. HIV infection can cause an MND-like syndrome due to central nervous system (CNS) involvement de novo or during antiretroviral therapy (ART) due to CNS escape. We present two cases: one with a classic amyotrophic lateral sclerosis (ALS) phenotype, which was the manifestation of symptomatic CNS escape from ART, and the second with a primary lateral sclerosis (PLS) phenotype associated with underlying HIV infection. A systematic review of published literature of people living with HIV (PLHIV) who developed ALS/ MND was conducted using the PubMed, Embase, and Lilacs databases. A total of 91 cases were found, 89 of which were obtained from 37 articles, and two were included from our own case series. In patients with HIV-associated MND, 63 patients reviewed had a classic ALS phenotype followed by progressive muscular atrophy variant (12), progressive bulbar palsy (8), PLS (7) and bulbar onset ALS (1). Neuroimaging, electrophysiology, cerebrospinal fluid (CSF) analysis, CSF and serum HIV viral load, and CD4 count investigations were used for diagnosis. Following the initiation or modification of antiretroviral therapy (ART), approximately 70% exhibited an improvement or a stable disease course. HIV-associated MND is a rare condition that can occur in both ART-naive individuals and those on treatment. A proportion of cases (~ 70%) show improvement with ART. Accurate diagnosis requires the exclusion of opportunistic infections, which remains a critical yet challenging aspect of managing this condition.}, } @article {pmid40037468, year = {2025}, author = {Peck, A and Dadi, A and Yavarow, Z and Alfano, LN and Anderson, D and Arkin, MR and Chou, TF and D'Ambrosio, ES and Diaz-Manera, J and Dudley, JP and Elder, AG and Ghoshal, N and Hart, CE and Hart, MM and Huryn, DM and Johnson, AE and Jones, KB and Kimonis, V and Kiskinis, E and Lee, EB and Lloyd, TE and Mapstone, M and Martin, A and Meyer, H and Mozaffar, T and Onyike, CU and Pfeffer, G and Pindon, A and Raman, M and Richard, I and Rubinsztein, DC and Schiava, M and Schütz, AK and Shen, PS and Southworth, DR and Staffaroni, AM and Taralio-Gravovac, M and Weihl, CC and Yao, Q and Ye, Y and Peck, N}, title = {2024 VCP International Conference: Exploring multi-disciplinary approaches from basic science of valosin containing protein, an AAA+ ATPase protein, to the therapeutic advancement for VCP-associated multisystem proteinopathy.}, journal = {Neurobiology of disease}, volume = {207}, number = {}, pages = {106861}, pmid = {40037468}, issn = {1095-953X}, support = {R01 CA293084/CA/NCI NIH HHS/United States ; R21 NS123631/NS/NINDS NIH HHS/United States ; Z99 DK999999/ImNIH/Intramural NIH HHS/United States ; }, mesh = {*Valosin Containing Protein/genetics/metabolism ; Humans ; Frontotemporal Dementia/genetics ; Animals ; Osteitis Deformans/genetics ; Myositis, Inclusion Body/genetics ; Congresses as Topic ; }, abstract = {Valosin-containing protein (VCP/p97) is a ubiquitously expressed AAA+ ATPase associated with numerous protein-protein interactions and critical cellular functions including protein degradation and clearance, mitochondrial homeostasis, DNA repair and replication, cell cycle regulation, endoplasmic reticulum-associated degradation, and lysosomal functions including autophagy and apoptosis. Autosomal-dominant missense mutations in the VCP gene may result in VCP-associated multisystem proteinopathy (VCP-MSP), a rare degenerative disorder linked to heterogeneous phenotypes including inclusion body myopathy (IBM) with Paget's disease of bone (PDB) and frontotemporal dementia (FTD) or IBMPFD, amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), parkinsonism, Charcot-Marie Tooth disease (CMT), and spastic paraplegia. The complexity of VCP-MSP makes collaboration among stakeholders essential and necessitates a multi-disciplinary approach. The 2024 VCP International Conference was hosted at Caltech between February 22 and 25. Co-organized by Cure VCP Disease and Dr. Tsui-Fen Chou, the meeting aimed to center the patient as a research partner, harmonize diverse stakeholder engagement, and bridge the gap between basic and clinical neuroscience as it relates to VCP-MSP. Over 100 multi-disciplinary experts attended, ranging from basic scientists to clinicians to patient advocates. Attendees discussed genetics and clinical presentation, cellular and molecular mechanisms underlying disease, therapeutic approaches, and strategies for future VCP research. The conference included three roundtable discussions, 29 scientific presentations, 32 scientific posters, nine patient and caregiver posters, and a closing discussion forum. The following conference proceedings summarize these sessions, highlighting both the identified gaps in knowledge and the significant strides made towards understanding and treating VCP diseases.}, } @article {pmid40037332, year = {2025}, author = {Belbasis, L and Morris, S and van Duijn, C and Bennett, D and Walters, R}, title = {Mendelian randomization identifies proteins involved in neurodegenerative diseases.}, journal = {Brain : a journal of neurology}, volume = {148}, number = {7}, pages = {2412-2428}, pmid = {40037332}, issn = {1460-2156}, support = {/DH_/Department of Health/United Kingdom ; //NIHR/ ; /WT_/Wellcome Trust/United Kingdom ; 203141/Z/16/Z/WT_/Wellcome Trust/United Kingdom ; //NHS/ ; }, mesh = {Humans ; *Mendelian Randomization Analysis/methods ; *Neurodegenerative Diseases/genetics/metabolism/blood ; Genome-Wide Association Study ; Proteomics/methods ; Male ; Parkinson Disease/genetics ; Female ; Genetic Predisposition to Disease ; }, abstract = {Proteins are involved in multiple biological functions. High-throughput technologies have allowed the measurement of thousands of proteins in population biobanks. In this study, we aimed to identify proteins related to Alzheimer's disease, Parkinson's disease, multiple sclerosis and amyotrophic lateral sclerosis by leveraging large-scale genetic and proteomic data. We performed a two-sample cis Mendelian randomization study by selecting instrumental variables for the abundance of >2700 proteins measured by either Olink or SomaScan platforms in plasma from the UK Biobank and the deCODE Health Study. We also used the latest publicly available genome-wide association studies for the neurodegenerative diseases of interest. The potentially causal effect of proteins on neurodegenerative diseases was estimated based on the Wald ratio. We tested 13 377 protein-disease associations, identifying 169 associations that were statistically significant (5% false discovery rate). Evidence of co-localization between plasma protein abundance and disease risk (posterior probability > 0.80) was identified for 61 protein-disease pairs, leading to 50 unique protein-disease associations. Notably, 23 of 50 protein-disease associations corresponded to genetic loci not previously reported by genome-wide association studies. The two-sample Mendelian randomization and co-localization analysis also showed that APOE abundance in plasma was associated with three subcortical volumes (hippocampus, amygdala and nucleus accumbens) and white matter hyper-intensities, whereas PILRA and PILRB abundance in plasma was associated with caudate nucleus volume. Our study provided a comprehensive assessment of the effect of the human proteome that is currently measurable through two different platforms on neurodegenerative diseases. The newly associated proteins indicated the involvement of complement (C1S and C1R), microglia (SIRPA, SIGLEC9 and PRSS8) and lysosomes (CLN5) in Alzheimer's disease; the interleukin-6 pathway (CTF1) in Parkinson's disease; lysosomes (TPP1), blood-brain barrier integrity (MFAP2) and astrocytes (TNFSF13) in amyotrophic lateral sclerosis; and blood-brain barrier integrity (VEGFB), oligodendrocytes (PARP1), node of Ranvier and dorsal root ganglion (NCS1, FLRT3 and CDH15) and the innate immune system (CR1, AHSG and WARS) in multiple sclerosis. Our study demonstrates how harnessing large-scale genomic and proteomic data can yield new insights into the role of the plasma proteome in the pathogenesis of neurodegenerative diseases.}, } @article {pmid40036711, year = {2025}, author = {Nguyen, ML and Haddad, A and Law-Ye, B and Hesters, A}, title = {Uncommon Spinal Cord MRI Findings in a Patient With Early-Onset Amyotrophic Lateral Sclerosis: A Case Report.}, journal = {Neurology}, volume = {104}, number = {7}, pages = {e213503}, doi = {10.1212/WNL.0000000000213503}, pmid = {40036711}, issn = {1526-632X}, } @article {pmid40036368, year = {2025}, author = {Ervilha Pereira, P and De Bleecker, JL and Bogaert, E and Dermaut, B}, title = {Myopathic aggregation-prone variants in the TDP-43 prion-like domain: genetics paving the way.}, journal = {Brain : a journal of neurology}, volume = {148}, number = {6}, pages = {1876-1887}, doi = {10.1093/brain/awaf076}, pmid = {40036368}, issn = {1460-2156}, support = {3G0H8318//Research Foundation Flanders/ ; G0AC724N//Research Foundation Flanders/ ; //Funds W. Pyleman and Cremers-Opdebeeck/ ; 2023-J1141680-231086//King Baudouin Foundation/ ; 01N10319//Ghent University Special Research Fund/ ; //Ghent University Fund/ ; }, mesh = {Humans ; *DNA-Binding Proteins/genetics/metabolism ; *TDP-43 Proteinopathies/genetics/pathology ; Animals ; *Muscular Diseases/genetics/pathology ; *Prions/genetics/metabolism ; Amyotrophic Lateral Sclerosis/genetics ; }, abstract = {While neuropathological and genetic studies have established the crucial involvement of TDP-43 proteinopathy in the pathogenesis of amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD) and related neurodegenerative disorders, multiple studies have described the presence of TDP-43 inclusions in muscular disorders, including inclusion body myositis but also other related rimmed vacuole myopathies. In addition, TAR DNA-binding protein-43 (TDP-43) has been reported to be essential in normal muscle physiology as it is implicated in the formation of so-called amyloid-like myogranules during normal muscle regeneration after injury. However, genetic evidence supporting a primary role for TDP-43 proteinopathy in muscle disease has been missing. In the present review we highlight recent landmark discoveries linking novel pathogenic TDP-43 variants [p.(W385IfsX10) and p.(G376V)] within the prion-like domain with unusual aggregation-propensity and muscle rather than neuronal pathology. We discuss these studies in the context of known TDP-43-related pathways in ALS/FTD pathogenesis and show how they challenge some widely accepted views such as ALS as a pure neurogenic presynaptic neuromuscular disease and the direct correlation between TDP-43 aggregation-propensity and neurotoxicity. Finally, we discuss TDP-43 as part of a growing list of RNA-binding proteins including hnRNPA2B1 and hnRNPA1 as genetic causes of myopathies and relate this to the idea of 'multisystem proteinopathy'.}, } @article {pmid40034872, year = {2025}, author = {Wagner, H and Mlček, M and Krupičková, P and Popkova, M and Mejstrik, A and Boucek, T and Michálek, P and Kittnar, O and Belohlavek, J}, title = {Adrenaline has a limited effect on myocardial microvascular blood flow: A randomised experimental study in a porcine cardiac arrest model.}, journal = {Resuscitation plus}, volume = {22}, number = {}, pages = {100893}, pmid = {40034872}, issn = {2666-5204}, abstract = {BACKGROUND: Adrenaline (ADR) is a cornerstone of advanced life support (ALS) in cardiac arrest (CA), although its neurologically favourable survival outcomes remain unclear. ADR increases coronary perfusion pressure (CPP), with levels >15 mmHg associated with successful defibrillation. This study aimed to elucidate the relationship between ADR, myocardial microvascular blood flow, and resuscitation outcomes using a porcine CA model simulating refractory ventricular fibrillation (VF).

METHODS: This study involved 24 domestic pigs. After instrumentation, intubation, and baseline measurements, the animals were randomised into the ADR or control (saline) groups. VF was induced, and cardiopulmonary resuscitation was initiated using continuous mechanical chest compressions and ventilation. ADR or saline was administered following ALS guidelines. After 21 min of ALS, defibrillation was performed. Continuous measurements of arterial and venous blood pressures using an electrocardiogram and index of myocardial resistance (IMR) and transit mean time (Tmn) 1 min before and after each injection or peak blood pressure were recorded and compared between the groups. CPP-IMR, amplitude spectrum area (AMSA)-IMR, CPP-Tmn, and AMSA-Tmn correlations were assessed.

RESULTS: Compared with six animals in the control group, three in the ADR group achieved a return of spontaneous circulation. No difference was observed in IMR or AMSA; however, significant increases in CPP and arterial end-diastolic blood pressure were observed at several time points. Tmn differed between groups only at two time points.

CONCLUSION: Repeated ADR doses during prolonged ALS simulating refractory VF did not improve myocardial microvascular blood flow, as measured using IMR, despite leading to an increase in CPP.}, } @article {pmid40034089, year = {2025}, author = {Vaage, AM and Holmøy, T and Dahl, J and Stigum, H and Meyer, HE and Nakken, O}, title = {Statin Use and Amyotrophic Lateral Sclerosis Survival: A Population-Based Cohort Study.}, journal = {European journal of neurology}, volume = {32}, number = {3}, pages = {e70095}, pmid = {40034089}, issn = {1468-1331}, support = {//ALS Norway/ ; 2022050//Helse Sør-Øst RHF/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/mortality/drug therapy/epidemiology ; Female ; Male ; *Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use ; Middle Aged ; Norway/epidemiology ; Aged ; Cohort Studies ; Registries ; Adult ; }, abstract = {BACKGROUND: Dyslipidemia is common in amyotrophic lateral sclerosis (ALS). Statin use has been associated with both favorable and poor prognoses. We assessed whether statin use affects ALS survival.

METHODS: We linked four Norwegian health surveys (1972-2003) with mandatory national registries to obtain information on premorbid health, ALS diagnosis, and death. Using the Norwegian Prescribed Drug Registry, we identified participants who had dispensed statins pre- and post-diagnosis. We first compared pre-diagnosis statin discontinuation rates between ALS patients and matched controls. Flexible parametric models were then fitted to estimate the relationship between statin use and survival time in ALS, using restricted mean survival time and hazard ratio (HR) as effect measures.

RESULTS: A total of 524 patients (43% female) with ALS were included. Mean time from ALS diagnosis to death or end of study was 2.0 (SD 2.1) years. A substantial proportion of statin users (21%) discontinued statins during the year leading up to diagnosis. This group was characterized by poorer ALS prognosis compared to those adhering to statins and were included as statin users in our analysis. After adjusting for sex, age, birth year, riluzole use and premorbid smoking status, body mass index, and total cholesterol levels, statin use was not associated with ALS survival. The estimated mean survival difference comparing statin users to non-users was 0.74 (95% CI -5.98 to 7.47) months, corresponding to a HR of 0.97 (95% CI 0.77-1.23).

CONCLUSION: Statin use was not associated with ALS survival, suggesting that statins should not routinely be discontinued in ALS.}, } @article {pmid40033997, year = {2025}, author = {Poulsen, NS and Kraglund, LR and Vissing, J}, title = {Physical training of wheelchair users with neuromuscular disorders: A systematic review.}, journal = {Journal of neuromuscular diseases}, volume = {12}, number = {3}, pages = {330-341}, doi = {10.1177/22143602241313114}, pmid = {40033997}, issn = {2214-3602}, mesh = {Humans ; *Wheelchairs ; *Neuromuscular Diseases/rehabilitation ; *Exercise Therapy/methods ; }, abstract = {OBJECTIVE: Wheelchair users with neuromuscular disorders have symptoms related to the disease and complications to the sedentary lifestyle, such as constipation and lower back pain. Physical training might be beneficial. This systematic review investigates the potential benefits and harms of physical training for wheelchair users with neuromuscular disorders.

METHODS: We systematically searched PubMed including studies published until July 2024.

INCLUSION CRITERIA: 1) participants with a neuromuscular disorder, 2) at least 60% of participants in a study were wheelchair users, 3) physical training and its effects were investigated, 4) studies were prospective, and 5) English language was used. Non-peer-reviewed articles were excluded. Search results were screened by title, abstract, and full text. Two independent authors assessed the quality with the Downs and Black Quality Index.

RESULTS: We included 14 studies of 140 patients from 5 types of neuromuscular disorders (Duchenne muscular atrophy, spinal muscular atrophy, limb-girdle muscular atrophy, facioscapulohumeral muscular dystrophy, and amyotrophic lateral sclerosis). The mean quality was low (16/32) due to flaws in study design, selection bias, and power. Even though many were of low quality and lacked descriptions of adverse events, they all showed positive effects. Most studies investigated physical training of mastication or respiration with improvements in both. Other findings were improvements in endurance, extremity strength, and range of motion.

CONCLUSIONS: Physical training of wheelchair users with neuromuscular disorders is not well investigated. Physical training seems safe and beneficial, but training of respiratory and masticatory muscles is the only well-documented exercise modality that can be advised in patients with Duchenne Muscular Dystrophy or Duchenne Muscular Dystrophy/Spinal Muscular Atrophy, respectively. Larger, high-quality trials, including other neuromuscular disorders, are needed to assess the effects and adverse events of physical training.}, } @article {pmid40033457, year = {2025}, author = {Kallambettu, V and York, JD and Vasilopolous, T and Hutcheson, K and Plowman, E}, title = {Validation of the Dynamic Imaging Grade of Swallowing Toxicity for Amyotrophic Lateral Sclerosis.}, journal = {Neurogastroenterology and motility}, volume = {37}, number = {6}, pages = {e70008}, pmid = {40033457}, issn = {1365-2982}, support = {R01 CA271223/CA/NCI NIH HHS/United States ; R01 NS100859/NS/NINDS NIH HHS/United States ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/complications/diagnostic imaging/physiopathology ; *Deglutition Disorders/etiology/diagnostic imaging/diagnosis/physiopathology ; Male ; Female ; Middle Aged ; Aged ; Reproducibility of Results ; Fluoroscopy/methods ; Deglutition/physiology ; Disease Progression ; Severity of Illness Index ; }, abstract = {INTRODUCTION: Although dysphagia is prevalent in persons with amyotrophic lateral sclerosis (pALS) and is associated with morbidity and mortality, no validated outcomes currently exist for the gold standard videofluoroscopy (VF) exam. We therefore sought to psychometrically validate the Dynamic Imaging Grade of Swallowing Toxicity (DIGEST) scale in pALS.

METHODS: One hundred pALS attended a research evaluation and underwent a standardized VF and validated clinical outcomes of oral intake (FOIS), perceived swallowing impairment (EAT-10), and ALS disease progression (ALSFRS-Revised). Duplicate, independent, and blinded VF ratings were completed using the DIGEST and MBSImP scales. Weighted kappa, ANOVAs (Tukey's HSD, Welch's correction), and Chi-square analyses were performed to determine intra- and inter-rater reliability, criterion validity, and construct validity of the DIGEST scale for use in pALS.

RESULTS: The mean age was 64.4(SD = 10.4), 50% were male, and the average ALS duration was 28.2 months (SD = 22.2). Excellent intra-rater (kappa = 0.92-1.0) and inter-rater (kappa = 0.94) reliability were noted for DIGEST ratings. DIGEST grades significantly discriminated pharyngeal pathophysiology (MBSImP, F(3,96) = 24.7, p < 0.0001), perceived dysphagia (EAT-10, F(3,40) = 20.8, p < 0.0001), oral intake (FOIS, X[2]:25.4, df = 3, p < 0.0001), ALS bulbar disease progression (ALSFRS-bulbar, F(3,93) = 20.8, p < 0.0001) with main effects noted for all analyses. Post hoc pairwise comparisons noted differences across all DIGEST grades with the exception of DIGEST 2 versus 3 (moderate vs. severe dysphagia), p > 0.05.

CONCLUSIONS: These data confirm that the DIGEST scale is a reliable and valid VF outcome for use in pALS to distinguish normal versus impaired swallowing and mild versus moderate or severe dysphagia for use in clinical practice and as a clinical trial endpoint marker.}, } @article {pmid40033250, year = {2025}, author = {Lu, C and Huang, XX and Huang, M and Liu, C and Xu, J}, title = {Mendelian randomization of plasma proteomics identifies novel ALS-associated proteins and their GO enrichment and KEGG pathway analyses.}, journal = {BMC neurology}, volume = {25}, number = {1}, pages = {82}, pmid = {40033250}, issn = {1471-2377}, mesh = {*Amyotrophic Lateral Sclerosis/genetics/blood ; Humans ; *Mendelian Randomization Analysis/methods ; *Proteomics/methods ; Genome-Wide Association Study ; *Blood Proteins/genetics/metabolism ; Biomarkers/blood ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neurological disorder with an increasing incidence rate. Despite advances in ALS research over the years, the precise etiology and pathogenic mechanisms remain largely elusive.

OBJECTIVE: To identify novel plasma proteins associated with ALS through Mendelian randomization methods in large-scale plasma proteomics and to provide potential biomarkers and therapeutic targets for ALS treatment.

METHODS: This study employed a large-scale plasma proteomic Mendelian randomization approach using genetic data from 80,610 individuals of European ancestry (including 20,806 ALS patients and 59,804 controls) derived from a genome-wide association study (GWAS). Protein quantitative trait loci (pQTLs) data were obtained from Ferkingstad et al. (2021), which measured 4,907 proteins in 35,559 Icelandic individuals. Multiple Mendelian randomization (MR) techniques were utilized, including weighted median, MR-Egger, Wald ratio, inverse-variance weighting (IVW), basic model, and weighted model. Heterogeneity was evaluated using Cochran's Q test. Horizontal pleiotropy was assessed through the MR-Egger intercept test and MR-PRESSO outlier detection. Sensitivity analysis was performed via leave-one-out analysis.

RESULTS: MR analysis revealed potential causal associations between 491 plasma proteins and ALS, identifying 19 novel plasma proteins significantly linked to the disease. Proteins such as C1QC, UMOD, SLITRK5, ASAP2, TREML2, DAPK2, ARHGEF10, POLM, SST, and SIGLEC1 showed positive correlations with ALS risk, whereas ADPGK, BTNL9, COLEC12, ADGRF5, FAIM, CRTAM, PRSS3, BAG5, and PSMD11 exhibited negative correlations. Reverse MR analyses confirmed that ALS negatively correlates with ADPGK and ADGRF5 expression. Enrichment analyses, including Gene Ontology (GO) functional analysis, indicated involvement in critical biological processes such as external encapsulating structure organization, extracellular matrix organization, chemotaxis, and taxis. KEGG pathway analysis highlighted significant enrichment in the PI3K-Akt signaling pathway, cytokine-cytokine receptor interactions, and axon guidance.

CONCLUSION: This study enhances the understanding of ALS pathophysiology and proposes potential biomarkers and mechanistic insights for therapeutic development. Future research should explore the clinical translation of these findings to improve ALS patient outcomes and quality of life.}, } @article {pmid40032505, year = {2025}, author = {Callegaro, S and Manera, U and Canosa, A and Grassano, M and Palumbo, F and Cabras, S and Matteoni, E and Di Pede, F and De Mattei, F and De Marchi, F and Mazzini, L and Moglia, C and Calvo, A and Chiò, A and Vasta, R}, title = {Another brick in our knowledge of ALS causes: a population-based study of residential clustering.}, journal = {Journal of neurology, neurosurgery, and psychiatry}, volume = {96}, number = {8}, pages = {821-822}, doi = {10.1136/jnnp-2024-335670}, pmid = {40032505}, issn = {1468-330X}, } @article {pmid40032118, year = {2025}, author = {Dang, M and Wu, L and Zhang, X}, title = {Structural insights and milestones in TDP-43 research: A comprehensive review of its pathological and therapeutic advances.}, journal = {International journal of biological macromolecules}, volume = {306}, number = {Pt 3}, pages = {141677}, doi = {10.1016/j.ijbiomac.2025.141677}, pmid = {40032118}, issn = {1879-0003}, mesh = {Humans ; *DNA-Binding Proteins/chemistry/metabolism/genetics ; Animals ; *Neurodegenerative Diseases/metabolism/pathology/genetics/therapy ; Amyotrophic Lateral Sclerosis/metabolism/pathology/genetics ; }, abstract = {Transactive response (TAR) DNA-binding protein 43 (TDP-43) is a critical RNA/DNA-binding protein involved in various cellular processes, including RNA splicing, transcription regulation, and RNA stability. Mislocalization and aggregation of TDP-43 in the cytoplasm are key features of the pathogenesis of several neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and Alzheimer's disease (AD). This review provides a comprehensive retrospective and prospective analysis of TDP-43 research, highlighting structural insights, significant milestones, and the evolving understanding of its physiological and pathological functions. We delineate five major stages in TDP-43 research, from its initial discovery as a pathological hallmark in neurodegeneration to the recent advances in understanding its liquid-liquid phase separation (LLPS) behavior and interactions with cellular processes. Furthermore, we assess therapeutic strategies targeting TDP-43 pathology, categorizing approaches into direct and indirect interventions, alongside modulating aberrant TDP-43 LLPS. We propose that future research will focus on three critical areas: targeting TDP-43 structural polymorphisms for disease-specific therapeutics, exploring dual temporal-spatial modulation of TDP-43, and advancing nano-therapy. More importantly, we emphasize the importance of understanding TDP-43's functional repertoire at the mesoscale, which bridges its molecular functions with broader cellular processes. This review offers a foundational framework for advancing TDP-43 research and therapeutic development.}, } @article {pmid40031506, year = {2024}, author = {Guo, J and Chen, D and Zeng, X and Liu, X and Wang, X and Teng, S and Ye, K and Sun, X and Zhang, S and He, J and Fan, D and Liu, Y}, title = {A Multi-branch Attention-based Deep Learning Method for ALS Identification with sMRI Data.}, journal = {Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference}, volume = {2024}, number = {}, pages = {1-4}, doi = {10.1109/EMBC53108.2024.10782847}, pmid = {40031506}, issn = {2694-0604}, mesh = {*Amyotrophic Lateral Sclerosis/diagnostic imaging/diagnosis ; Humans ; *Deep Learning ; *Magnetic Resonance Imaging/methods ; *Spinal Cord/diagnostic imaging/pathology ; Algorithms ; *Image Processing, Computer-Assisted/methods ; }, abstract = {The structural Magnetic resonance imaging (sMRI) of spinal cord plays a significant role in the clinical diagnosis of Amyotrophic Lateral Sclerosis (ALS). But due to small cross-sectional area in the axial plane and long sagittal/coronal expansion of spinal cord, the diagnosis of ALS using sMRI of spinal cord has remained largely at the stage of morphological observation. In this study, a Multi-branch attention-based deep learning method is proposed to solve this problem. Multi-branch framework is utilized to extract general features of all levels of spinal cord for challenging of long sagittal and coronal expansion of spinal cord, and attention module coupled with multi-scale module in each branch is applied to extract multi-scale features and pay more attention to the important regions of the spinal cord in the axial plane. Experiments show that the proposed method obtains better performance in ALS identification, which implies that the proposed method can extract features of important region in the spinal cord and could be helpful to find more regions sensitive for ALS disease identification.}, } @article {pmid40030850, year = {2025}, author = {Hong, Z and Yi, S and Deng, M and Zhong, Y and Zhao, Y and Li, L and Zhou, H and Xiao, Y and Hu, X and Niu, L}, title = {Transcranial Focused Ultrasound Modifies Disease Progression in SOD1G93A Mouse Model of Amyotrophic Lateral Sclerosis.}, journal = {IEEE transactions on ultrasonics, ferroelectrics, and frequency control}, volume = {72}, number = {2}, pages = {191-201}, doi = {10.1109/TUFFC.2024.3525143}, pmid = {40030850}, issn = {1525-8955}, mesh = {Animals ; *Amyotrophic Lateral Sclerosis/therapy/physiopathology/diagnostic imaging/genetics ; Mice ; Disease Models, Animal ; Mice, Transgenic ; *Ultrasonic Therapy/methods ; Superoxide Dismutase-1/genetics ; Disease Progression ; Muscle, Skeletal/physiopathology ; Male ; Motor Cortex ; Humans ; Elasticity Imaging Techniques ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressively worsening neurodegenerative condition with very few treatment options available. Ultrasound neuromodulation offers promising benefits for treating neurodegenerative diseases such as Parkinson's and Alzheimer's diseases. However, the effects and underlying mechanisms of ultrasound neuromodulation on ALS remain unclear. A head-mounted ultrasound neuromodulation system was developed to noninvasively stimulate the motor cortex of symptomatic mice carrying the G93A human SOD1 mutation (SOD $1^{\text {G93A} } $) for four weeks. Motor performance was assessed through the rotarod locomotor test, grip strength test, and open field test. In addition, the effect of ultrasound stimulation on the elastic modulus of gastrocnemius muscle atrophy was measured using real-time shear wave elastography (SWE). Subsequently, the brain tissues of the mice were harvested. Gastrocnemius morphology was examined using hematoxylin-eosin and Gomori aldehyde-fuchsin (GAF) staining. The number of neurons and the phenotype of microglia in the motor cortex were observed by immunohistochemical analysis. Ultrasound therapy delayed disease onset by 10.7% and increased the lifespan by 6.7% in SOD $1^{\text {G93A} } $ mice by reduction of neuronal loss and enhancement of M2 microglia in the motor cortex. Furthermore, we found significant improvements in motor function for ultrasound-treated mice. More importantly, ultrasound stimulation ameliorated gastrocnemius muscle atrophy in the SOD $1^{\text {G93A} } $ mice. These results revealed the neuroprotective effects of ultrasound against the disease pathogenesis of SOD $1^{\text {G93A} } $ mice. Transcranial ultrasound neuromodulation provides an innovative tool for the intervention and treatment of neurodegenerative diseases.}, } @article {pmid40030617, year = {2024}, author = {Jiang, Y and Li, K and Liang, Y and Chen, D and Tan, M and Li, Y}, title = {Daily Assistance for Amyotrophic Lateral Sclerosis Patients Based on a Wearable Multimodal Brain-Computer Interface Mouse.}, journal = {IEEE transactions on neural systems and rehabilitation engineering : a publication of the IEEE Engineering in Medicine and Biology Society}, volume = {PP}, number = {}, pages = {}, doi = {10.1109/TNSRE.2024.3520984}, pmid = {40030617}, issn = {1558-0210}, abstract = {Amyotrophic lateral sclerosis (ALS) is a chronic, progressive neurodegenerative disease that mainly causes damage to upper and lower motor neurons. This leads to a progressive deterioration in the voluntary mobility of the upper and lower extremities in ALS patients, which underscores the pressing need for an assistance system to facilitate communication and body movement without relying on neuromuscular function. In this paper, we developed a daily assistance system for ALS patients based on a wearable multimodal brain-computer interface (BCI) mouse. The system comprises two subsystems: a mouse system assisting the upper extremity and a wheelchair system based on the mouse system assisting the lower extremity. By wearing a BCI headband, ALS patients can control a computer cursor on the screen with slight head rotation and eye blinking, and further operate a computer and drive a wheelchair with specially designed graphical user interfaces (GUIs). We designed operating tasks that simulate daily needs and invited ALS patients to perform the tasks. In total, 15 patients with upper extremity limitations performed the mouse system task and 9 patients with lower extremity mobility issues performed the wheelchair system task. To our satisfaction, all the participants fully accomplished the tasks and average accuracies of 83.9% and 87.0% for the two tasks were achieved. Furthermore, workload evaluation using NASA Task Load Index (NASA-TLX) revealed that the participants experienced a low workload when using the system. The experimental results demonstrate that the proposed system provides ALS patients with effective daily assistance and shows promising long-term application prospects.}, } @article {pmid40030616, year = {2024}, author = {Bista, S and Coffey, A and Mitchell, M and Fasano, A and Dukic, S and Buxo, T and Giglia, E and Heverin, M and Muthuraman, M and Carson, RG and Lowery, M and Manus, LM and Hardiman, O and Nasseroleslami, B}, title = {Abnormal EEG spectral power and coherence measures during pre-motor stage in Amyotrophic Lateral Sclerosis.}, journal = {IEEE transactions on neural systems and rehabilitation engineering : a publication of the IEEE Engineering in Medicine and Biology Society}, volume = {PP}, number = {}, pages = {}, doi = {10.1109/TNSRE.2024.3523109}, pmid = {40030616}, issn = {1558-0210}, abstract = {Amyotrophic lateral sclerosis (ALS) is a multisystem neurodegenerative disorder characterized by progressive motor decline. Studies of electroencephalographic (EEG) activity during rest and motor execution have captured network changes in ALS. However, the nature of network-level impairment in the pre-motor activity in ALS remains unclear. Assessing the (dys)function of motor networks engaged prior to motor output is essential for understanding the motor pathophysiology in ALS. We recorded EEG in 22 people with ALS (PwALS) and 16 age-matched healthy controls during rest and isometric pincer-grip tasks. EEG spectral power and coherence were calculated during rest, pre-motor stage, and motor execution. In PwALS, significantly higher event-related spectral perturbations were observed compared to controls over electrodes representing a) contralateral prefrontal and parietal regions in theta band during pre-motor stage, b) contralateral parietal and ipsilateral motor regions in high-beta band during motor execution. Similarly, spectral coherence revealed abnormal EEG connectivity within 1) sensorimotor network during rest in theta band, 2) (pre)motor networks during pre-motor stage in low-alpha and high-beta bands, 3) Fronto-parietal networks during execution in high-beta band. Furthermore, the abnormal EEG connectivity during rest and execution (but not during pre-motor stage) showed significant negative correlation with clinical ALS-functional-rating-scale scores. Combining abnormal EEG connectivity from rest, pre-motor, and execution stages provided more powerful discrimination between patients and controls with a uniquely higher contribution of measures pertaining to the pre-motor stage. The results indicate that pre-motor functional activity reflects a different and unique aspect of network impairment, with potential for inclusion as biomarker candidates in ALS.}, } @article {pmid40030411, year = {2024}, author = {Mishra, S and Chatterjee, D and Kanekar, N}, title = {Topological Gait Analysis: A New Framework and Its Application to the Study of Human Gait.}, journal = {IEEE journal of biomedical and health informatics}, volume = {28}, number = {12}, pages = {7040-7053}, doi = {10.1109/JBHI.2024.3427700}, pmid = {40030411}, issn = {2168-2208}, mesh = {Humans ; *Gait Analysis/methods ; Adult ; Male ; Female ; Middle Aged ; Parkinson Disease/physiopathology ; *Gait/physiology ; Amyotrophic Lateral Sclerosis/physiopathology ; Aged ; Huntington Disease/physiopathology ; Gait Disorders, Neurologic/physiopathology ; }, abstract = {OBJECTIVE: This study introduces a physiologically driven topological gait analysis (TGA) framework to gain insights into pathological gait.

METHODS: A publicly available gait dataset consisting of four groups: healthy adults, people with Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS) was used. The topological properties of the configuration space of three gait parameters were studied by approximating the underlying distribution through a Gaussian kernel-based density estimation technique. Thereafter, sublevel sets of the density estimate were analyzed using cubical persistence homology.

RESULTS: Three new features were constructed: 1. Probability density estimates (PDEs) that characterize the distribution of gait parameters over their configuration space. Healthy adults exhibited a unimodal distribution, while people with neurodegenerative disorders displayed a multi-modal distribution. 2. Persistence entropy plots that summarize changes in the PDEs and characterize the uncertainty in the underlying distribution. Gait of healthy adults was concentrated at higher entropy values as opposed to neurodegenerative gait. 3. A number that captures disease severity trends.

CONCLUSIONS: Topological features in PD and HD indicate a 'bias' to a certain set of gait configurations. This lack of exploration may reflect poor planning of the underlying topology, resulting in outward manifestations of impaired gait. The lower variegations in PDEs in ALS compared to PD and HD suggest that the planning of the topology of gait may occur at higher levels of the neural architecture.

SIGNIFICANCE: TGA offers characterization of gait at a hitherto uncharted level, potentially serving neuromotor markers for early diagnosis and personalized rehabilitation protocols.}, } @article {pmid40029926, year = {2025}, author = {Panda, P and Mohanty, S and Gouda, SR and Baral, TC and Mohanty, A and Nayak, J and Mohapatra, R}, title = {Advanced strategies for enhancing the neuroprotective potential of curcumin: delivery systems and mechanistic insights in neurodegenerative disorders.}, journal = {Nutritional neuroscience}, volume = {}, number = {}, pages = {1-26}, doi = {10.1080/1028415X.2025.2472773}, pmid = {40029926}, issn = {1476-8305}, abstract = {Background: Curcumin, a polyphenolic compound derived from Curcuma longa, exhibits significant neuroprotective potential due to its diverse pharmacological properties.Objective: This review explores curcumin's role in modulating key pathological mechanisms underlying neurodegenerative disorders such as Alzheimer's, Parkinson's diseases, Amyotrophic Lateral Sclerosis, Huntington's Disease and Prion Disease.Methods: A comprehensive analysis of curcumin's molecular interactions, including its effects on amyloid-beta (Aβ) aggregation, tau hyperphosphorylation, neuroinflammation, oxidative stress, and metal-induced neurotoxicity, was conducted. Additionally, strategies to overcome its low bioavailability and blood-brain barrier (BBB) permeability were evaluated.Results: Curcumin inhibits Aβ aggregation and promotes disaggregation, reducing amyloid plaque formation in Alzheimer's disease. It modulates glial cell activity, attenuating neuroinflammation and fostering a neuroprotective environment. By interacting with tau proteins, curcumin prevents hyperphosphorylation and neurofibrillary tangle formation. As a potent antioxidant, it scavenges reactive oxygen species, mitigating oxidative stress-related neuronal damage. Its metal-chelating properties further diminish neurotoxicity by sequestering iron and copper ions. Despite its limited bioavailability and BBB permeability, curcumin's therapeutic efficacy can be enhanced using nanocarriers such as nanoparticles, liposomes, and micelles, which improve solubility, stability, and brain penetration.Conclusion: Curcumin's multifaceted neuroprotective mechanisms make it a promising candidate for preventing or slowing neurodegenerative disease progression. Advanced drug delivery systems hold potential for overcoming its pharmacokinetic limitations, paving the way for future clinical applications.}, } @article {pmid40029669, year = {2025}, author = {Carroll, E and Scaber, J and Huber, KVM and Brennan, PE and Thompson, AG and Turner, MR and Talbot, K}, title = {Drug repurposing in amyotrophic lateral sclerosis (ALS).}, journal = {Expert opinion on drug discovery}, volume = {20}, number = {4}, pages = {447-464}, pmid = {40029669}, issn = {1746-045X}, mesh = {*Drug Repositioning/methods ; *Amyotrophic Lateral Sclerosis/drug therapy/physiopathology ; Humans ; Animals ; Drug Discovery/methods ; Translational Research, Biomedical/methods ; }, abstract = {INTRODUCTION: Identifying treatments that can alter the natural history of amyotrophic lateral sclerosis (ALS) is challenging. For years, drug discovery in ALS has relied upon traditional approaches with limited success. Drug repurposing, where clinically approved drugs are reevaluated for other indications, offers an alternative strategy that overcomes some of the challenges associated with de novo drug discovery.

AREAS COVERED: In this review, the authors discuss the challenge of drug discovery in ALS and examine the potential of drug repurposing for the identification of new effective treatments. The authors consider a range of approaches, from screening in experimental models to computational approaches, and outline some general principles for preclinical and clinical research to help bridge the translational gap. Literature was reviewed from original publications, press releases and clinical trials.

EXPERT OPINION: Despite remaining challenges, drug repurposing offers the opportunity to improve therapeutic options for ALS patients. Nevertheless, stringent preclinical research will be necessary to identify the most promising compounds together with innovative experimental medicine studies to bridge the translational gap. The authors further highlight the importance of combining expertise across academia, industry and wider stakeholders, which will be key in the successful delivery of repurposed therapies to the clinic.}, } @article {pmid40029136, year = {2025}, author = {Revi, N and Nandeshwar, M and Harijan, D and Sankaranarayanan, SA and Joshi, M and Prabusankar, G and Rengan, AK}, title = {Acridine Benzimidazolium Derivatives Induced Protective Microglia Polarization and In Silico TDP-43 Interaction─Potential Implications for Amyotrophic Lateral Sclerosis.}, journal = {ACS chemical neuroscience}, volume = {16}, number = {6}, pages = {1103-1116}, doi = {10.1021/acschemneuro.4c00791}, pmid = {40029136}, issn = {1948-7193}, mesh = {*Microglia/drug effects/metabolism ; *Amyotrophic Lateral Sclerosis/metabolism/drug therapy ; Animals ; *DNA-Binding Proteins/metabolism/antagonists & inhibitors ; Humans ; Mice ; *Acridines/pharmacology/chemistry ; *Benzimidazoles/pharmacology/chemistry ; Molecular Docking Simulation ; *Neuroprotective Agents/pharmacology ; Cell Polarity/drug effects ; }, abstract = {Abnormal protein aggregation and associated neuronal-glial cell cytotoxicity lead to a plethora of neurodegenerative disorders. Most of the earlier investigations on understanding neurodegenerative disease progression and cure focused on neuronal damage and restoration potential. With increased evidence on the role of glial cells like microglia and astrocytes in mediating these disorders, more studies are dedicated to understanding the role of inflammatory responses mediated by glial cells and how they lead to neuroinflammation. Amyotrophic lateral sclerosis (ALS) is a late-onset neurodegenerative disorder caused by TDP-43 aggregation that affects motor neurons. Pro-inflammatory microglia are considered to aggravate the disorder condition. In the current study, a previously reported molecule with TDP-43 inhibition, 3,3'-(acridine-4,5-diylbis(methylene))bis(1-(carboxymethyl)imidazol-3-ium) dibromide salt (AIM4), is analyzed for its microglia polarization properties along with two other derivatives, 3,3'-(acridine-4,5-diylbis(methylene))bis(1-(2-ethoxy-2-oxoethyl)benzimidazol-3-ium) dibromide salt (ABE) and 3,3'-(acridine-4,5-diylbis(methylene))bis(1-(carboxymethyl)benzoimidazol-3-ium) dibromide salt (ABA). The 3,3'-(acridine-4,5-diylbis(methylene))bis(1-(2-ethoxy-2-oxoethyl)benzimidazol-3-ium) dibromide salt (ABE) and 3,3'-(acridine-4,5-diylbis(methylene))bis(1-(carboxymethyl) benzimidazol-3-ium) dibromide salt (ABA) display the increased ability to maintain microglial cells to anti-inflammatory state and TDP-43 binding as compared to 3,3'-(acridine-4,5-diylbis(methylene)) bis(carboxymethyl)imidazolium dibromide salt (AIM4). This was confirmed from total nitrite levels, mitochondria membrane potential analysis, and molecular docking studies. The selected pro-inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) displayed decreased levels, and anti-inflammatory cytokines IL-4 and IL-10 displayed increased levels, however not very significantly, upon treatment with all acridine derivatives. The compounds were investigated on lipopolysaccharides (LPS)-triggered mouse microglial cells and Danio rerio embryos displaying no significant cytotoxicity and physiological changes (cardiac rhythm), respectively. In molecular docking studies, alanine at 315 mutated to glutamate of TDP-43 directly interacts with AIM4. However, π-σ interactions of the aromatic backbone of acridine in ABE and ABA with 313 phenylalanine of TDP-43 along with hydrogen bonds formed between 309, 310 glycine amino acids and imidazolium bromide side chains rendered a stronger binding of these acridine derivatives with the protein potentially inhibiting fibrillation. Conclusion: ABA, ABE, and AIM4 maintain microglia in an anti-inflammatory state. However, more studies are required to understand its interaction with TDP-43 and the mechanism of its anti-inflammatory nature.}, } @article {pmid40028680, year = {2025}, author = {Khosravi, S and Amini, E and Emamikhah, M and Alavi, A and Lang, AE and Rohani, M}, title = {Motor Neuron Involvement in Two ATP13A2-Related Families: ALS And HSP-Like Phenotypes.}, journal = {Movement disorders clinical practice}, volume = {12}, number = {6}, pages = {852-857}, pmid = {40028680}, issn = {2330-1619}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/physiopathology ; Iran ; *Motor Neuron Disease/genetics ; Mutation/genetics ; Pedigree ; Phenotype ; *Proton-Translocating ATPases/genetics ; *Spastic Paraplegia, Hereditary/genetics/physiopathology ; Parkinsonian Disorders ; }, abstract = {BACKGROUND: Mutations in the ATP13A2 gene have been implicated in various neurodegenerative disorders, including Kufor-Rakeb syndrome (KRS), neuronal ceroid lipofuscinosis (NCL), hereditary spastic paraplegia (HSP), and amyotrophic lateral sclerosis (ALS). This report presents two Iranian families with ATP13A2 variants exhibiting atypical features of KRS.

CASES: We highlight four patients from two consanguineous Iranian families with mutations in the ATP13A2 gene presenting with variable features of motor neuron disease as well as juvenile-onset parkinsonism, and cognitive decline. The onset of symptoms ranged from 11 to 29 years, with initial manifestations including gait disturbance, postural instability, and cognitive impairment. As the disease progressed, patients developed a range of neurological signs, such as dystonia, spasticity, and dysarthria.

CONCLUSION: This report expands the phenotypic spectrum of ATP13A2-related disorders, highlighting the potential overlap of symptoms associated with KRS, ALS, and HSP.}, } @article {pmid40027730, year = {2025}, author = {Pant, DC and Lone, MA and Parameswaran, J and Ma, F and Dutta, P and Wang, Z and Park, J and Verma, S and Hornemann, T and Jiang, J}, title = {Lack of motor defects and ALS-like neuropathology in heterozygous Sptlc1 Exon 2 deletion mice.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {40027730}, issn = {2692-8205}, support = {R01 AG068247/AG/NIA NIH HHS/United States ; UL1 TR000454/TR/NCATS NIH HHS/United States ; }, abstract = {Mutations in the human SPTLC1 gene have recently been linked to early onset amyotrophic lateral sclerosis (ALS), characterized by global atrophy, motor impairments, and symptoms such as tongue fasciculations. All known ALS-linked SPTLC1 mutations cluster within exon 2 and a specific variant, c.58G>T, results in exon 2 skipping. However, it is unclear how the exon 2 deletion affects SPTLC1 function in vivo and contributes to ALS pathogenesis. Leveraging the high genomic sequence similarity between mouse and human SPTLC1, we created a novel mouse model with a CRISPR/Cas9-mediated deletion of exon 2 in the endogenous murine Sptlc1 locus. While heterozygous mice did not develop motor defects or ALS-like neuropathology, homozygous mutants died prematurely. These findings indicate that Sptlc1 ΔExon2 heterozygous mice do not replicate the disease phenotype but provide valuable insights into SPTLC1 biology and serve as a useful resource for future mechanistic studies.}, } @article {pmid40027671, year = {2025}, author = {Woo, E and Tasnim, F and Kawamata, H and Manfredi, G and Konrad, C}, title = {Investigation of mitochondrial phenotypes in motor neurons derived by direct conversion of fibroblasts from familial ALS subjects.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {40027671}, issn = {2692-8205}, support = {R01 NS139141/NS/NINDS NIH HHS/United States ; R35 NS122209/NS/NINDS NIH HHS/United States ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease of motor neurons, leading to fatal muscle paralysis. Familial forms of ALS (fALS) account for approximately 10% of cases and are associated with mutations in numerous genes. Alterations of mitochondrial functions have been proposed to contribute to disease pathogenesis. Here, we employed a direct conversion (DC) technique to generate induced motor neurons (iMN) from skin fibroblasts to investigate mitochondrial phenotypes in a patient-derived disease relevant cell culture system. We converted 7 control fibroblast lines and 17 lines harboring the following fALS mutations, SOD1[A4V], TDP-43[N352S], FUS[R521G], CHCHD10[R15L], and C9orf72 repeat expansion. We developed new machine learning approaches to identify iMN, analyze their mitochondrial function, and follow their fate longitudinally. Mitochondrial and energetic abnormalities were observed, but not all fALS iMN lines exhibited the same alterations. SOD1[A4V], C9orf72, and TDP-43[N352S] iMN had increased mitochondrial membrane potential, while in CHCHD10[R15L] cells membrane potential was decreased. TDP-43[N352S] iMN displayed changes in mitochondrial morphology and increased motility. SOD1[A4V], TDP-43[N352S], and CHCHD10[R15L] iMN had increased oxygen consumption rates and altered extracellular acidification rates, reflecting a hypermetabolic state similar to the one described in sporadic ALS fibroblasts. FUS[R521G] mutants had decreased ATP/ADP ratio, suggesting impaired energy metabolism. We then tested the viability of iMN and found decreases in survival in SOD1[A4V], C9orf72, and FUS[R521G], which were corrected by small molecules that target mitochondrial stress. Together, our findings reinforce the role of mitochondrial dysfunction in ALS and indicate that fibroblast-derived iMN may be useful to study fALS metabolic alterations. Strengths of the DC iMN approach include low cost, speed of transformation, and the preservation of epigenetic modifications. However, further refinement of the fibroblasts DC iMN technique is still needed to improve transformation efficiency, reproducibility, the relatively short lifespan of iMN, and the senescence of the parental fibroblasts.}, } @article {pmid40027590, year = {2025}, author = {Untalan, LGV and Malanog, JPD and Jamora, RDG}, title = {Evaluating YouTube as a source of information on amyotrophic lateral sclerosis.}, journal = {Digital health}, volume = {11}, number = {}, pages = {20552076251324439}, pmid = {40027590}, issn = {2055-2076}, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a rare neurodegenerative disease that leads to progressive motor weakness and eventual death. Recent years have seen an increase in online information on ALS, with the popular video platform YouTube becoming a prominent source. We aimed to evaluate the quality, reliability, actionability, and understandability of ALS videos on YouTube.

METHODS: A search was performed using the keyword "Amyotrophic Lateral Sclerosis" on YouTube. A total of 240 videos were viewed and assessed by two independent raters. Video characteristics such as type of uploader, views, likes, comments, and Video Power Index were also collected.

RESULTS: Videos had moderate to low quality and reliability (Global Quality Scale [GQS] and modified DISCERN [mDISCERN] median 2.5), and poor understandability and actionability (PEMAT total median 8.5). Among the general video characteristics, only length of video showed a significant positive correlation across the tools (with mDISCERN [p < 0.001]; with GQS [p < 0.001]; with PEMAT [p < 0.001]). Videos from physicians (p = 0.024, sig <0.05), other healthcare professionals (p = 0.017, sig <0.05), and educational channels (p = 0.001, sig <0.05) had better quality when compared to others.

CONCLUSION: YouTube videos are a poor source of information for ALS as videos tend to have moderate to low quality and reliability and are poorly understandable and actionable. Longer videos, and videos uploaded by those in the healthcare and educational fields, were found to perform relatively better. Thus, when using YouTube, caution and careful attention to the video characteristics are recommended.}, } @article {pmid40027570, year = {2025}, author = {Giorgio, A and Ciracì, E and De Luca, M and Stella, G and Giorgio, V}, title = {Hepatic abscess and hydatid liver cyst: European infectious disease point of view.}, journal = {World journal of hepatology}, volume = {17}, number = {2}, pages = {103325}, pmid = {40027570}, issn = {1948-5182}, abstract = {This manuscript is based on a recent study by Pillay et al that was published in recently. Liver abscesses can be caused by rare potentially life-threatening infections of either bacterial or parasitic origin. The incidence rate in Europe is lower than in developing countries, but it is a major complication with high morbidity, particularly in immunocompromised patients. They are most frequently caused by Enterobacterales infections, but hypervirulent Klebsiella strains are an emerging problem in Western countries. Amoebiasis has been a public health problem in Europe, primarily imported from other endemic foci. At the same time, this infection is becoming an emerging disease, as the number of infected patients who have not traveled to endemic areas is rising. Treatment options for hydatid liver cyst include chemotherapy, open or laparoscopic surgery, percutaneous treatment (percutaneous aspiration, re-aspiration and injection and its modification) and ''wait and watch'' strategy. Most hydatid liver cyst patients in Pillay et al's study received surgical treatment, but several studies have confirmed the safety and efficacy of percutaneous aspiration, re-aspiration and injection.}, } @article {pmid40025671, year = {2025}, author = {Wang, Y and Li, C and Yang, Y and Ma, C and Zhao, X and Li, J and Wei, L and Li, Y}, title = {A Surface-Enhanced Raman Spectroscopy Platform Integrating Dual Signal Enhancement and Machine Learning for Rapid Detection of Veterinary Drug Residues in Meat Products.}, journal = {ACS applied materials & interfaces}, volume = {17}, number = {10}, pages = {16202-16212}, doi = {10.1021/acsami.4c21938}, pmid = {40025671}, issn = {1944-8252}, mesh = {*Spectrum Analysis, Raman/methods ; *Machine Learning ; *Veterinary Drugs/analysis ; *Meat Products/analysis ; *Drug Residues/analysis ; Animals ; Metal Nanoparticles/chemistry ; Food Contamination/analysis ; }, abstract = {The detection and quantification of veterinary drug residues in meat remain a significant challenge due to the complex background interference inherent to the meat matrix, which compromises the stability and accuracy of spectroscopic analysis. This study introduces an advanced label-free surface-enhanced Raman spectroscopy (SERS) platform for the precise identification and quantification of veterinary drugs. By employing a dual enhancement strategy involving sodium borohydride activation and calcium ion-deuterium oxide guidance, this platform achieves the efficient capture and signal amplification of drug molecules on highly active nanoparticles. High-quality SERS spectra were obtained for carprofen, doxycycline hydrochloride, chloramphenicol, and penicillin G sodium salt, enabling accurate classification and interference suppression. In addition, the application of machine learning algorithms, including PCA-LDA, heatmap, and decision tree modeling, allows for accurate differentiation of mixed drug samples. Quantitative analyses in meat samples were achieved through Raman intensity ratios and multivariate curve resolution-alternate least-squares (MCR-ALS) analysis, with results showing high consistency with high-performance liquid chromatography (HPLC) measurements. These findings highlight the potential of this SERS-based platform for accurate and rapid detection of multicomponent veterinary drug residues in complex food matrices.}, } @article {pmid40025240, year = {2025}, author = {Maier, A and Kettemann, D and Weyen, U and Grehl, T and Schulte, PC and Steinbach, R and Rödiger, A and Weydt, P and Petri, S and Wolf, J and Grosskreutz, J and Koch, JC and Weishaupt, JH and Rosseau, S and Norden, J and Körtvélyessy, P and Koch, B and Holm, T and Hildebrandt, B and Schumann, P and Walter, B and Riitano, A and Münch, C and Meyer, T and Spittel, S}, title = {Provision, cough efficacy and treatment satisfaction of mechanical insufflation-exsufflation in a large multicenter cohort of patients with amyotrophic lateral sclerosis.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {7360}, pmid = {40025240}, issn = {2045-2322}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/complications/therapy/physiopathology ; *Cough/therapy/etiology ; Male ; Female ; Middle Aged ; *Insufflation/methods ; Aged ; *Patient Satisfaction ; Treatment Outcome ; Longitudinal Studies ; Germany ; Adult ; }, abstract = {In patients with amyotrophic lateral sclerosis (ALS), mechanical insufflation-exsufflation (MI-E) addresses cough deficiency to achieve major therapeutic goals: improving costal muscle and joint function, reducing atelectasis through insufflation, and clearing bronchial secretions via exsufflation. Despite its perceived benefits, there is limited systematic research on MI-E provision, symptom alleviation, or patient satisfaction. The research platform Ambulanzpartner coordinated this longitudinal observational study conducted in 12 German ALS centers from July 2018 to September 2023. Patients were enrolled based on ALS-related cough deficiency requiring MI-E therapy. The study recorded provision, reasons for withholding MI-E, clinical parameters, therapy frequency, subjective cough deficiency, and symptomatic relief. Satisfaction with MI-E therapy was determined by the likelihood of recommendation. Out of 694 ALS patients indicated for MI-E, 527 (75.9%) received the therapy. The primary reason for non-provision was that the patient had died before provision (n = 66 of 167; 39.5%). These patients were significantly more affected as represented by higher progression rates and lower cough peak flows (CPF) at the time of MI-E indication (p < 0.05). Most patients who received MI-E used it daily (n = 290 of 370; 78.4%). Self-assessed cough deficiency correlated with clinical measurements, especially for patients with higher deficits. At follow-up visits, patients reported reduced cough deficiency (p < 0.001). Frequent MI-E use was linked to greater symptom relief and higher likelihood of recommending the therapy. This study highlights the symptomatic and palliative potential of MI-E therapy for ALS patients.}, } @article {pmid40025162, year = {2025}, author = {Hiew, JY and Lim, YS and Liu, H and Ng, CS}, title = {Integrated transcriptomic profiling reveals a STING-mediated Type II Interferon signature in SOD1-mutant amyotrophic lateral sclerosis models.}, journal = {Communications biology}, volume = {8}, number = {1}, pages = {347}, pmid = {40025162}, issn = {2399-3642}, support = {#SED000125//Monash University Malaysia (Monash Malaysia)/ ; #PM010CNI000148//International Brain Research Organization (IBRO)/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology/immunology ; Animals ; Humans ; Mice ; *Superoxide Dismutase-1/genetics/metabolism ; *Membrane Proteins/metabolism/genetics ; Disease Models, Animal ; Gene Expression Profiling ; *Mutation ; *Transcriptome ; *Interferon-gamma/genetics/metabolism ; Induced Pluripotent Stem Cells/metabolism ; Male ; Female ; }, abstract = {Inflammation is a hallmark of amyotrophic lateral sclerosis (ALS), particularly in cases with SOD1 mutations. Using integrative transcriptomics, we analyzed gene expression changes in mouse models throughout progression, human induced-pluripotent stem cells (hiPSCs), and post-mortem spinal cord tissue from ALS patients. We identified a conserved upregulation of interferon (IFN) genes and IFN-stimulating genes (ISGs) in both mouse models and human ALS, with a predominance Type I IFNs (IFN-α/β) in mice and Type II IFNs (IFN-γ) in humans. In mouse models, we observed robust and sustained upregulation of Type I and II ISGs, including ATF3, beginning at disease onset stage and persisting throughout disease progression. Single-cell transcriptomics further pinpointed vascular endothelial cells as a major source of ISGs. Furthermore, we found that the STING-TBK1 axis is essential for the induction of Type II ISGs in ALS, as its deletion impaired their expression. Our study uncovers a conserved ISGs signature across ALS models and patients, highlighting the potential role of innate immune activation in ALS pathogenesis. These findings suggest that ISGs may serve as potential biomarkers and therapeutic targets for ALS.}, } @article {pmid40024955, year = {2025}, author = {Masood, S and Almas, MS and Hassan, SSU and Tahira, S and Fiaz, MH and Minhas, UEA and Zafar, HMQ and Masood, M}, title = {Safety and efficacy of arimoclomol in amyotrophic lateral sclerosis: a systematic review and meta-analysis.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {46}, number = {7}, pages = {2985-2994}, pmid = {40024955}, issn = {1590-3478}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy ; Randomized Controlled Trials as Topic ; *Neuroprotective Agents/adverse effects/therapeutic use ; Treatment Outcome ; Hydroxylamines ; }, abstract = {OBJECTIVES: Amyotrophic Lateral Sclerosis (ALS) is a debilitating motor neuron disorder characterized by muscle weakness, atrophy, and spasticity. This meta-analysis aims to assess the safety and efficacy of Arimoclomol in patients with ALS.

METHOD: A comprehensive literature search was conducted on 3 databases to discover articles published up to August 2024. Included studies were randomized controlled trials (RCTs). Data was analysed using Review Manager (v5.4). Cochrane Risk of Bias-2 (RoB-2) was adopted to assess the quality of RCTs.

RESULTS: A total of 359 patients were analysed, with 239 individuals in the Arimoclomol group and 120 individuals in the placebo group. The pooled analysis of the primary outcome, change in Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) score from baseline, did not demonstrate a statistically significant difference favoring the Arimoclomol group (MD = 0.4495; 95% CI: -0.39, 1.27; p = 0.30). Similarly, secondary outcomes, including the Combined Assessment of Function and Survival (CAFS) rank score (MD = 1.00; 95% CI: -2.68, 4.67; p = 0.60), increase in transaminases (RR = 1.05; 95% CI: 0.19, 5.70; p = 0.95), mortality rate (RR = 0.86; 95% CI: 0.55, 1.34; p = 0.50), and adverse events (RR = 0.86; 95% CI: 0.55, 1.34; p = 0.50), showed no statistically significant differences between the groups.

CONCLUSION: This study does not conclusively demonstrate that Arimoclomol has beneficial effects on ALS patients' physical functionality but shows promise for safety. Further clinical trials are needed to explore the neuroprotective effects of Arimoclomol in the treatment of ALS.}, } @article {pmid40024058, year = {2025}, author = {Baumgarten, BR and Freye, CE}, title = {Use of Fisher's Ratio assisted multivariate curve resolution- alternating least squares for discovery-based analysis using ultrahigh pressure liquid chromatography-high resolution mass spectrometry.}, journal = {Journal of chromatography. A}, volume = {1747}, number = {}, pages = {465812}, doi = {10.1016/j.chroma.2025.465812}, pmid = {40024058}, issn = {1873-3778}, mesh = {Chromatography, High Pressure Liquid/methods ; *Mass Spectrometry/methods ; Least-Squares Analysis ; Multivariate Analysis ; Ponds/chemistry ; Pharmaceutical Preparations/analysis/chemistry ; }, abstract = {Non-targeted analysis of complex chemical mixtures can be difficult considering the convoluted nature of the matrix and the potential unknown chemical differences between samples or classes of samples. Ultrahigh pressure liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (UHPLC-QTOF) is an ideal technique to probe chemical differences for a wide variety of samples. While UHPLC-QTOF can discover minute chemical differences down to low part per billion (ppb) concentrations with a high degree of confidence, the application of high-resolution mass spectrometry can yield massive amounts of information (∼ 10 gb per sample) that cannot be analyzed manually. Therefore, the application of chemometric techniques is mandatory for the interrogation of complex samples. Fisher's ratio (FR) assisted multivariate curve resolution-alternating least squares (MCR-ALS) was used to the discover and identify the chemical differences between two classes of materials: 1) a pond water matrix and 2) the matrix spiked with a pharmaceutical standard mix containing 17 compounds. Thirteen of the seventeen spiked compounds were discovered using FR analysis, and then five were successfully deconvoluted using MCR-ALS wherein the number of curves chosen were automatically determined using singular value decomposition (SVD). The use of an automated FR assisted MCR-ALS will aid in discovering trace levels of chemical components without the need for the researcher to provide potentially biased input which will aid in non-targeted workflow.}, } @article {pmid40022663, year = {2025}, author = {Buckett, LE and Holdom, CJ and Howe, SL and McCombe, PA and Henderson, RD and Al-Chalabi, A and Steyn, FJ and Ngo, ST}, title = {Persistent high levels of perceived fatigue are not associated with hypermetabolism in patients with amyotrophic lateral sclerosis.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {26}, number = {5-6}, pages = {485-494}, doi = {10.1080/21678421.2025.2471429}, pmid = {40022663}, issn = {2167-9223}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism/complications/psychology/physiopathology ; Male ; Female ; *Fatigue/etiology/metabolism/diagnosis/psychology ; Middle Aged ; Prospective Studies ; Aged ; Disease Progression ; Severity of Illness Index ; Self Report ; Adult ; }, abstract = {Objective: Fatigue is a common symptom in amyotrophic lateral sclerosis (ALS). Little is known about factors that contribute to fatigue, and whether levels of fatigue change throughout disease course. We aimed to determine associations between self-reported perceived fatigue and metabolic and clinical features of ALS, and perceived fatigue over the course of disease. Methods: This prospective study was conducted between July 2017 and March 2024. Baseline measures of self-reported perceived fatigue, metabolic rate, and clinical measures of disease were assessed in 117 participants with clinically definite or probable ALS. For comparison, fatigue and metabolic rate were collected from 107 control participants. Perceived fatigue was determined using the Fatigue Severity Scale (FSS). Metabolic rate was assessed using indirect calorimetry. Functional capacity and clinical progression were assessed using the ALS Functional Rating Scale-Revised (ALSFRS-R). Results: Baseline levels of perceived fatigue were greater in people living with ALS (plwALS) when compared to controls (5.44 vs. 2.55; p < 0.01). Perceived fatigue was higher in plwALS with lower ALSFRS-R scores and was not associated with measures of metabolism. For most plwALS, perceived fatigue remained high as functional capacity worsened. Conclusion: Our findings confirm higher prevalence of perceived fatigue in plwALS, with persistently high FSS scores reported by most patients during follow-up. High levels of fatigue were not associated with hypermetabolism, suggesting that metabolic rate is unlikely to be a primary contributor. Results highlight a need for further research to identify factors that contribute to fatigue in ALS, and options for improved fatigue management.}, } @article {pmid40022581, year = {2025}, author = {Galvin, M and Heverin, M and Mac Domhnaill, É and Mcfarlane, R and Meldrum, D and Murray, D and Bolger, A and Connelly, J and Flynn, K and Fox, E and Gibbons, F and Hederman, L and Impey, S and O'Keefe, I and O'Meara, C and McKibben, D and Nicholson, M and Stephens, G and Van Dijk, J and Van Den Berg, L and Hardiman, O}, title = {Challenges and solutions to complex data governance issues in cross-national, cross-sectoral, multidisciplinary real world health research: a descriptive overview.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {26}, number = {sup1}, pages = {1-7}, doi = {10.1080/21678421.2024.2428927}, pmid = {40022581}, issn = {2167-9223}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy/epidemiology ; *Biomedical Research ; *Precision Medicine ; Europe ; *Data Management ; }, abstract = {Real-world clinical data is generated during clinical engagements. The collection and further processing and mining of clinical information requires consents and navigation of necessary and important data governance processes. PRECISION ALS is an academic industry programme that collects, collates and analyses clinical and para-clinical data from patients with ALS across 10 European sites. The infrastructure of PRECISION ALS represents a complex interplay of the clinical, governance, and technical frameworks. Incorporation of infrastructural and operational measures enables sophisticated cross-national, cross-sectoral and cross disciplinary health research. PRECISION ALS has established a range of domain expertise, technologies, governance and clinical data management practices that can be applied throughout the life cycle of patient data from generation, collation, delivery and secure storage for advanced analytics. PRECISION ALS is designed to move the field of ALS research to a true Precision Medicine based approach toward new and more effective therapeutics.}, } @article {pmid40021952, year = {2025}, author = {Hao, Y and Li, Z and Du, X and Xie, Q and Li, D and Lei, S and Guo, Y}, title = {Characterization and chemoproteomic profiling of protein O-GlcNAcylation in SOD1-G93A mouse model.}, journal = {Molecular medicine (Cambridge, Mass.)}, volume = {31}, number = {1}, pages = {82}, pmid = {40021952}, issn = {1528-3658}, support = {92478109//National Natural Science Foundation of China/ ; 82471451//National Natural Science Foundation of China/ ; ZR2024QB108//Shandong Provincial Natural Science Foundation/ ; 7222082//Beijing Municipal Natural Science Foundation，China/ ; }, mesh = {Animals ; Disease Models, Animal ; *Amyotrophic Lateral Sclerosis/metabolism/pathology/genetics ; Mice ; *Proteomics/methods ; *Acetylglucosamine/metabolism ; Mice, Transgenic ; *Superoxide Dismutase-1/genetics/metabolism ; Spinal Cord/metabolism/pathology ; *Protein Processing, Post-Translational ; Glycosylation ; Humans ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a devastating motor neuron disease. Protein O-linked β-N-acetylglucosamine (O-GlcNAc) modification has been found to affect the processing of several important proteins implicated in ALS. However, the overall level and cellular localization of O-GlcNAc during ALS progression are incompletely understood, and large-scale profiling of O-GlcNAcylation sites in this context remains unexplored.

METHODS: By using immunostaining analysis and chemoenzymatic labeling-based quantitative chemoproteomics, we assayed O-GlcNAcylation dynamics of lumbar spinal cords from SOD-G93A mice and their non-transgenic (NTG) littermates, the most widely used animal model for studying ALS pathogenesis.

RESULTS: We discovered that the global O-GlcNAcylation was significantly reduced at the disease end stage. Correlatively, a great increase of OGA was observed. Immunohistochemistry and immunofluorescence analysis showed a higher proportion of O-GlcNAc-positive neurons in the NTG group, while O-GlcNAc colocalization with astrocytes/microglia was elevated in SOD1-G93A mice. Moreover, we reported the identification of 568 high-confidence O-GlcNAc sites from end-stage SOD1-G93A and NTG mice. Of the 568 sites, 226-many of which occurred on neuronal function and structure-related proteins-were found to be dynamically regulated.

CONCLUSION: These data provide a valuable resource for dissecting the functional role of O-GlcNAcylation in ALS and shed light on promising therapeutic avenues for ALS. The chemoenzymatic labeling-based chemoproteomic approach is applicable for probing O-GlcNAc dynamics in various pathological processes.}, } @article {pmid40020551, year = {2025}, author = {Tafuri, B and Giugno, A and Nigro, S and Zoccolella, S and Barone, R and Tamburrino, L and Gnoni, V and Urso, D and Rollo, E and De Blasi, R and Logroscino, G}, title = {Radiomic alterations and clinical correlates of hypothalamic nuclei in ALS.}, journal = {Computers in biology and medicine}, volume = {189}, number = {}, pages = {109906}, doi = {10.1016/j.compbiomed.2025.109906}, pmid = {40020551}, issn = {1879-0534}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnostic imaging/physiopathology/pathology ; Male ; Female ; Middle Aged ; *Hypothalamus/diagnostic imaging ; Aged ; *Magnetic Resonance Imaging ; Retrospective Studies ; Adult ; Body Mass Index ; Radiomics ; }, abstract = {OBJECTIVE: The aim of this study is to analyze hypothalamic changes and clinical/metabolic correlates with a radiomic approach in Amyotrophic Lateral Sclerosis (ALS).

METHODS: We retrospectively identified 54 sporadic ALS patients and 53 matched controls. We compared radiomics features over hypothalamic subunits in T1-weighted. Semi-partial correlation (Spearman's correlation) assessed the relationship between Body Mass Index (BMI) and clinical scores with radiomics features. We considered only moderate correlations (rho>|0.4|).

RESULTS: Compared to HC, individuals with ALS showed significantly higher values of radiomic measures in the left Anterior-Inferior, Posterior and Inferior-Tubular hypothalamic subunits. Similarly, right hypothalamic nuclei reported significant differences in Anterior-Superior, Posterior and Inferior-Tubular nuclei. Two radiomics measures of randomness of the intensities in left Anterior-Inferior subunit showed highly significant correlation with greater BMI values. Higher local homogeneity of the right Inferior-Tubular subunit corresponded to higher ALS Functional Rating Scale-Revised (ALSFRS-r), while finer textures of the left Anterior-Superior subunit were negatively related with disease progression rate.

CONCLUSIONS: These results support the hypothesis that a degenerative process affecting hypothalamus in ALS extends beyond the atrophy process. Intriguingly, the close relationship between the entropy of left Anterior-Inferior nucleus and the higher BMI may further demonstrate the critical role of hypothalamus in eating abnormalities. Furthermore, the inhomogeneity of the right Inferior-Tubular subunit reflects a more severe clinical condition by ALSFRS-R. This work represents a significant advancement in the study of ALS and its association with hypothalamic changes through a novel radiological approach, uncovering new associations between sub-hypothalamic radiomic changes, anthropometric measures, and disease outcomes.}, } @article {pmid40019593, year = {2025}, author = {Dobroniak, CC and Lesche, V and Olgemöller, U and Beck, P and Lehmann, W and Spering, C}, title = {Surgical strategy for chest wall reconstruction secondary to cardiopulmonary resuscitation versus post-traumatic.}, journal = {European journal of trauma and emergency surgery : official publication of the European Trauma Society}, volume = {51}, number = {1}, pages = {122}, pmid = {40019593}, issn = {1863-9941}, mesh = {Humans ; *Cardiopulmonary Resuscitation/adverse effects ; Male ; *Flail Chest/surgery/etiology ; Female ; Middle Aged ; Retrospective Studies ; *Thoracic Wall/surgery ; *Rib Fractures/surgery ; Sternum/injuries/surgery ; Adult ; *Plastic Surgery Procedures/methods ; *Fracture Fixation, Internal/methods ; Aged ; Length of Stay/statistics & numerical data ; *Thoracic Injuries/surgery ; Germany ; Bone Plates ; Treatment Outcome ; }, abstract = {PURPOSE: In mechanically cardiopulmonary resuscitated (CPR) patients, chest compressions at the level of the 3rd to 5th rib on the sternum result in reproducibly similar injury patterns: parasternal osteochondral dissociation (OCS) on both sides in combination with a sternal fracture with or without an additional serial rib fracture in the anterolateral column (ALS). This injury biomechanically impairs physiological breathing, resulting in an inverse breathing pattern. Trauma patients, on the other hand, often show a mixed pattern depending on the location of the main energy. The aim of the study was to evaluate the surgical technique of chest wall reconstruction (CWR) using transsternal refixation of the 5th rib on both sides in combination with plate osteosynthesis of the sternum and to analyze its success in comparison to the surgical strategy of CWR in the context of a traumatic genesis.

METHOD: Data acquisition was performed using medical records of a Level I Trauma Centre in Germany and compare patients with radiologically or clinically diagnosed flail chest as a result of cardiopulmonary mechanical resuscitation (CPR). The retrospective study included patients in the period 2018-2023 after surgical CWR. The patients were either post-CPR (n = 29; CPR) or trauma patients (n = 36; trauma). The collective was described and analyzed using the digital patient file, as well as data on ICU stay and duration of ventilation or conversion to assisted ventilation modes, reason for chest wall instability, time of surgery, length of stay and mortality. As a long-term follow-up, body plethysmography was analyzed comparatively. Primary endpoints were mean length of stay in ICU, time to surgery, ventilator dependency and mortality rate. Secondary endpoints were time to transfer to rehabilitation, ventilation disorders and long term outcome.

RESULTS: In the period 65 patients (48 m, 17w) were included, 29 of whom had been mechanically resuscitated (CPR), 36 formed to post-traumatic cohort (trauma). The CPR were significantly older (69 vs. 58 years; p-value 0.003). The duration from CPR to surgery was on average significantly longer than trauma to surgery (16.76 vs. 4.11 days). The mean length of stay in ICU were 30 days (trauma) and 45 days for CPR (significantly longer, p-value 0.0008). The mean duration of ventilation was 188 h for trauma and 593 h for CPR. Extubation or conversion to assisted, relevant de-escalating ventilation modes was possible in both groups after a mean of 38 h post-OP. Among the CPR patients, 4 died in hospital (hospital mortality: CPR 20.7% vs. trauma 5.6%), 7 (30%) were transferred to an early clinical rehabilitation and 10 were discharged to home or follow-up treatment. In the case of trauma, 5 (14.7%) were transferred to an early clinical rehabilitation and 20 were discharged to home or follow-up treatment. Bodyplethysmography 6 months after CPR / trauma showed no differences in both collectives with regard to ventilation disorders. Diffusion was prolonged in both groups, presumably due to the healing process of lungs contusion. Both showed no restriction disorders.

CONCLUSION: Chest wall reconstruction, including plate osteosynthesis of the sternum in combination with transsternal fixation of the 5th rib on both sides can largely restore physiological respiratory mechanics immediately after surgery and accelerate the weaning success. In the management of patients after CPR, the initial diagnosis which had indicated resuscitation, is the main focus and can often be an obstacle to extubation. Nevertheless, independent breathing can be accelerated by restoring the biomechanics through early surgical treatment using CWR and saves long-term ICU stays with the potential for further complication and resource consumption. CWR forms the essential basis for early rehabilitation of the underlying cause of resuscitation. Ventilation disorders do not occur after surgical CWR, even during the course of the procedure.}, } @article {pmid40019589, year = {2025}, author = {Shaw, SK and Sravani, N and Sharma, A and Anand, J}, title = {Assessment of probable zones of agricultural land suitability based on MCDM, probabilistic, and data-driven approach in Krishna District, India.}, journal = {Environmental monitoring and assessment}, volume = {197}, number = {3}, pages = {339}, pmid = {40019589}, issn = {1573-2959}, mesh = {*Agriculture/statistics & numerical data ; Conservation of Natural Resources/methods ; Decision Making ; *Decision Support Techniques ; Ecosystem ; Geographic Information Systems ; India ; Meteorological Concepts ; Remote Sensing Technology ; }, abstract = {Agricultural land evaluation is essential for crop cultivation for fostering a sustainable and productive agricultural system. To address this issue, this current study implements geographic information system (GIS)-based analytical hierarchy process (AHP), frequency ratio (FR), Shannon entropy (SE), and evidential belief function (EBF) models for possible identification of agricultural land in Krishna district, India. Eight thematic layers viz. rainfall, temperature, soil texture, slope, soil moisture index, organic matter content, groundwater level, and land use/land cover (LULC) exhibit their relative contribution toward the agricultural land suitability (ALS) assessment. A total of 56 groundwater wells are considered to prepare well inventory map. Then, 70% (40) and 30% (16) wells are taken to perform accuracy assessment of the proposed methods in training and validation phase respectively by receiver operating characteristics (ROC) curve and Seed Cell Area Index (SCAI) method. Four distinct classes of ALS have been delineated by each model viz. poor, moderate, high, and very high. AHP (79.05%) and SE (89.94%) showcases their effectiveness in delineating highly suitable agricultural land constituting higher area. Whereas EBF and FR model identifies 33.35% and 27% area of this district as moderate to poor ALS respectively. AUC value reveals that AHP (AUC = 0.701) method can be highly convenient in training phase, whereas EBF (AUC = 0.626) model evaluates average predictive strength for ALS assessment in validation phase for this study area. Outcomes of SCAI method demonstrate higher classification accuracy of SE model indicating higher suitability of bivariate approaches in accurate prediction. Results of this research significantly develop useful perception for the sustainable use and management of agricultural land of Krishna district with higher crop production. This will also help the Agricultural and Irrigation department of this district to build applicative plan for effective utilization of agricultural land with optimized use of available water resources.}, } @article {pmid40019378, year = {2025}, author = {Li, X and Jin, S and Wang, D and Wu, Y and Tang, X and Liu, Y and Yao, T and Han, S and Sun, L and Wang, Y and Hou, SX}, title = {Accumulation of Damaging Lipids in the Arf1-Ablated Neurons Promotes Neurodegeneration through Releasing mtDNA and Activating Inflammatory Pathways in Microglia.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {12}, number = {16}, pages = {e2414260}, pmid = {40019378}, issn = {2198-3844}, support = {2023YFA1800202//National Key Research and Development Program of China/ ; 82450108//National Natural Science Foundation of China/ ; 82203511//National Natural Science Foundation of China/ ; 82472817//National Natural Science Foundation of China/ ; }, mesh = {Animals ; *DNA, Mitochondrial/metabolism/genetics ; *Neurons/metabolism ; *Microglia/metabolism ; Mice ; *ADP-Ribosylation Factor 1/genetics/metabolism ; Mice, Knockout ; *Lipid Metabolism/genetics ; *Neurodegenerative Diseases/metabolism/genetics ; Mitochondria/metabolism ; Endoplasmic Reticulum Stress ; Autophagy ; *Inflammation/metabolism ; }, abstract = {Lipid metabolism disorders in both neurons and glial cells have been found in neurodegenerative (ND) patients and animal models. However, the pathological connection between lipid droplets and NDs remains poorly understood. The recent work has highlighted the utility of a neuron-specific Arf1-knockout mouse model and corresponding cells for elucidating the nexus between lipid metabolism disorders and amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS). In this study, it is found that Arf1 deficiency first induced surplus fatty acid synthesis through the AKT-mTORC1-SREBP1-FASN axis, which further triggered endoplasmic reticulum (ER)-mitochondrial stress cascade via calcium flux. The organelle stress cascade further caused mitochondrial DNA (mtDNA) to be released into cytoplasm. Concurrently, the FASN-driven fatty acid synthesis in the Arf1-deficient neurons might also induce accumulation of sphingolipids in lysosomes that caused dysfunction of autophagy and lysosomes, which further promoted lysosomal stress and mitochondria-derived extracellular vesicles (MDEVs) release. The released MDEVs carried mtDNA into microglia to activate the inflammatory pathways and neurodegeneration. The studies on neuronal lipid droplets (LDs) and recent studies of microglial LDs suggest a unified pathological function of LDs in NDs: activating the inflammatory pathways in microglia. This finding potentially provides new therapeutic strategies for NDs.}, } @article {pmid40017821, year = {2025}, author = {Dierksen, F and Geibel, JS and Albrecht, J and Hofer, S and Dechent, P and Hesse, AC and Frahm, J and Bähr, M and Koch, JC and Liman, J and Maier, IL}, title = {T1-relaxation times along the corticospinal tract as a diagnostic marker in patients with amyotrophic lateral sclerosis.}, journal = {Frontiers in neuroimaging}, volume = {4}, number = {}, pages = {1549727}, pmid = {40017821}, issn = {2813-1193}, abstract = {BACKGROUND AND PURPOSE: In the differential diagnostic workup of amyotrophic lateral sclerosis (ALS), magnetic resonance imaging (MRI) is primarily used to rule out significant differential diagnoses. So far, whole-brain T1-mapping has not been assessed as a diagnostic tool in this patient population.

METHODS: We investigated the diagnostic potential of a novel T1-mapping method based on real-time MRI with 0.5 mm in-plane resolution and 4s acquisition time per slice. The study included patients aged 18 to 90 years who met the revised El Escorial criteria for at least possible ALS. T1-relaxation times were measured along the corticospinal tract in predefined regions of interest.

RESULTS: Twenty-nine ALS-patients and 43 control group patients (CG) were included in the study. Median ALS Functional Rating Scale revised (ALSFRS-R) was 37 (IQR, 35-44) points and the mean duration from symptom onset to MRI was 21 ± 17 (SD) months. ALS patients showed significantly higher T1-relaxation times in all ROIs compared to CG with mean differences in the hand knob of 50 ms (p < 0.001), corona radiata 24 ms (p = 0.034), internal capsule 27 ms (p = 0.002) and midbrain peduncles 48 ms (p < 0.001). There was a consistent negative correlation between the ALSFRS-R and T1-relaxation times in all ROIs.

CONCLUSIONS: T1-relaxation times along the corticospinal tract are significantly elevated in ALS patients compared to CG and associated with lower ALSFRS-R. These results imply the analysis of T1-relaxation times as a promising diagnostic tool that can distinguish ALS patients from the control group. Ongoing longitudinal studies may provide deeper insights into disease progression and the effects of therapeutic interventions.}, } @article {pmid40017539, year = {2025}, author = {Mengistu, DY and Terribili, M and Pellacani, C and Ciapponi, L and Marzullo, M}, title = {Epigenetic regulation of TDP-43: potential implications for amyotrophic lateral sclerosis.}, journal = {Frontiers in molecular medicine}, volume = {5}, number = {}, pages = {1530719}, pmid = {40017539}, issn = {2674-0095}, abstract = {Amyotrophic lateral sclerosis (ALS) is a multifactorial neurodegenerative disease characterized by the progressive degeneration of motor neurons. One of the key pathogenic factors implicated in ALS is TDP-43 (TAR DNA-binding protein 43), an RNA-binding protein encoded by the TARDBP gene. Under normal physiological conditions, TDP-43 predominantly resides in the nucleus, where it plays a critical role in regulating gene expression, alternative splicing, RNA transport, and stability. In ALS, TDP-43 undergoes pathological mislocalization from the nucleus to the cytoplasm, disrupting its normal function and contributing to disease progression. The nuclear loss of TDP-43 leads to widespread dysregulation of RNA metabolism. Moreover, mislocalized TDP-43 aggregates in the cytoplasm, acquires toxic properties that sequester essential RNA molecules and proteins. Importantly, deviations in TDP-43 levels, whether excessive or reduced, can lead to cellular dysfunction, and contribute to disease progression, highlighting the delicate balance required for neuronal health. Emerging evidence suggests that epigenetic mechanisms may play a crucial role in regulating TARDBP expression and, consequently, TDP-43 cellular levels. Epigenetic modifications such as DNA methylation, histone modifications, and non-coding RNAs are increasingly recognized as modulators of gene expression and cellular function in neurodegenerative diseases, including ALS. Dysregulation of these processes could contribute to aberrant TARDBP expression, amplifying TDP-43-associated pathologies. This review explores and summarizes the recent findings on how specific epigenetic modifications influence TDP-43 expression and discusses their possible implications for disease progression.}, } @article {pmid40017137, year = {2025}, author = {Lovett, A and Chary, S and Babu, S and Bruneteau, G and Glass, JD and Karlsborg, M and Ladha, S and Mayl, K and McDermott, C and Bucelli, RC and Chiò, A and Ferguson, TA and Cochrane, T and Fradette, S and Smirnakis, K and Inra, J and Malek, S and Fanning, L}, title = {Serious Neurologic Adverse Events in Tofersen Clinical Trials for Amyotrophic Lateral Sclerosis.}, journal = {Muscle & nerve}, volume = {71}, number = {6}, pages = {1006-1015}, pmid = {40017137}, issn = {1097-4598}, support = {//Biogen/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy/genetics ; Middle Aged ; Male ; Female ; *Oligonucleotides/adverse effects/therapeutic use ; Adult ; Aged ; Superoxide Dismutase-1/genetics ; Myelitis/chemically induced ; Papilledema/chemically induced ; }, abstract = {INTRODUCTION/AIMS: Tofersen is approved for the treatment of amyotrophic lateral sclerosis (ALS) due to superoxide dismutase 1 mutations (SOD1-ALS). Here we report serious neurologic adverse events (AEs) that occurred in the tofersen clinical trials in people with SOD1-ALS.

METHODS: Serious neurologic AEs of myelitis, radiculitis, aseptic meningitis, and papilledema reported in the tofersen clinical trials are described. Serious AEs were defined according to International Conference for Harmonization guidelines, and neurologic AEs in clinical trials were diagnosed by investigators based on symptoms, clinical examination findings, and diagnostic workup.

RESULTS: Ten participants (approximately 7% of tofersen 100-mg-treated trial participants) experienced a total of 12 serious neurologic AEs-4 of myelitis, 2 of radiculitis, 2 of aseptic meningitis, and 4 of intracranial hypertension (ICH) and/or papilledema. All events but one resolved either spontaneously, with dosing interruption/modification, or with concomitant therapies. One event was ongoing but improved as of December 2022. While 3 events led to tofersen treatment discontinuation, all other participants were able to remain on treatment. No event was life-threatening or fatal.

DISCUSSION: Some antisense oligonucleotides (ASOs) have been described as having pro-inflammatory properties. Aseptic meningitis has been reported with nusinersen; however, myelitis, radiculitis, increased intracranial pressure, and papilledema have not been reported with ASO treatment. These neurologic AEs should be considered when assessing the overall benefit/risk of tofersen treatment for SOD1-ALS. Safety data from the open-label extension and expanded access program will continue to characterize these events and further inform the safety profile of tofersen in SOD1-ALS.}, } @article {pmid40016300, year = {2025}, author = {Xia, Y and Gregory, JM and Waldron, FM and Spence, H and Vallejo, M}, title = {Improving ALS detection and cognitive impairment stratification with attention-enhanced deep learning models.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {7045}, pmid = {40016300}, issn = {2045-2322}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/diagnostic imaging/complications ; *Deep Learning ; *Cognitive Dysfunction/diagnosis/diagnostic imaging ; Male ; Female ; Middle Aged ; Aged ; *Attention ; Neuroimaging/methods ; Brain/diagnostic imaging/pathology ; Neural Networks, Computer ; Frontotemporal Dementia/diagnosis ; Early Diagnosis ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurological disease marked by motor deterioration and cognitive decline. Early diagnosis is challenging due to the complexity of sporadic ALS and the lack of a defined risk population. In this study, we developed Miniset-DenseSENet, a convolutional neural network combining DenseNet121 with a Squeeze-and-Excitation attention mechanism, using 190 autopsy brain images from the Gregory Laboratory at the University of Aberdeen. The model distinguishes controls, ALS patients with no cognitive impairment, and ALS patients with cognitive impairment (ALS-frontotemporal dementia) with 97.37% accuracy, addressing a significant challenge in overlapping neurodegenerative disorders involving TDP-43 proteinopathy. Miniset-DenseSENet outperformed other transfer learning models, achieving a sensitivity of 1 and specificity of 0.95. These findings suggest that integrating transfer learning and attention mechanisms into neuroimaging can enhance diagnostic accuracy, enabling earlier ALS detection and improving patient stratification. This model has the potential to guide clinical decisions and support personalied therapeutic strategies.}, } @article {pmid40015858, year = {2025}, author = {Vijayarajan, VBA and Torra, J and Runge, F and de Jong, H and van de Belt, J and Hennessy, M and Forristal, PD}, title = {Confirmation and characterisation of ALS inhibitor resistant Poa trivialis from Ireland.}, journal = {Pesticide biochemistry and physiology}, volume = {208}, number = {}, pages = {106266}, doi = {10.1016/j.pestbp.2024.106266}, pmid = {40015858}, issn = {1095-9939}, mesh = {*Acetolactate Synthase/antagonists & inhibitors/genetics ; *Herbicide Resistance/genetics ; *Herbicides/pharmacology ; Ireland ; Sulfonylurea Compounds/pharmacology ; Sulfonamides/pharmacology ; Mutation ; Plant Proteins/genetics/antagonists & inhibitors/metabolism ; *Enzyme Inhibitors/pharmacology ; Plant Weeds/drug effects/genetics ; }, abstract = {Relying on one broad-spectrum product to control grass weeds has resulted in cases of resistance to acetolactate synthase (ALS) inhibitors in species that were not the primary target such as Poa trivialis (POATR), in wheat fields in Ireland. In this study, we have characterised ALS inhibitor resistance in two populations of POATR-R, suspected of being resistant, to (i) sulfonylurea (SUs)-mesosulfuron + iodosulfuron (the selecting agent), (ii) SU + sulfonylamino‑carbonyl-triazolinone (SCT)-mesosulfuron + propoxycarbazone, and (iii) triazolopyrimidine (TP)-pyroxsulam ALS chemistries. Resistant POATR-R populations showed ALS inhibitor cross-resistance associated with target-site resistance (TSR) mutations. Combined mutations (Pro-197 and Trp-574) were found in POATR-R plants; Trp-574-Leu in POATR-R1 conferring greater SUs, SU + SCT and TP (resistance index, RI >214) resistance, while Pro-197-Thr in POATR-R2 (RI >37) was associated with less resistance. The high levels of ALS inhibitor cross-resistance in POATR-R populations caused by TSR mutations are consistent with the ploidy status, as cytogenetic tests revealed that both the R and S populations were diploid (2n = 2× = 14). Cytochrome P450 inhibitor assays did not detect metabolism-based ALS resistance in POATR-R. Alternative herbicide modes of action, including acetyl-CoA carboxylase (pinoxaden, fenoxaprop, propaquizafop, cycloxydim or clethodim) and 5-enolpyruvylshikimate-3-phosphate synthase (glyphosate) inhibitors applied at the recommended label rate were highly effective on these resistant populations. Residual herbicides and cultural methods, as well as the judicious use of alternative in-crop herbicide options, should be prioritized as sustainable options for managing these ALS-resistant populations. This is first worldwide characterisation of resistance mechanisms in P. trivialis to ALS inhibitor chemistries.}, } @article {pmid40015855, year = {2025}, author = {Xu, Y and Xu, F and Li, Y and Wang, X and Han, Y and Zheng, M}, title = {Effects of Pro197 resistance mutations occurring in different acetolactate synthase (ALS) isozymes on Descurainia sophia L. resistance to tribenuron-methyl.}, journal = {Pesticide biochemistry and physiology}, volume = {208}, number = {}, pages = {106263}, doi = {10.1016/j.pestbp.2024.106263}, pmid = {40015855}, issn = {1095-9939}, mesh = {*Acetolactate Synthase/genetics/metabolism/antagonists & inhibitors ; *Arylsulfonates/pharmacology ; *Herbicide Resistance/genetics ; *Herbicides/pharmacology ; Mutation ; Isoenzymes/genetics/metabolism ; *Plant Proteins/genetics/metabolism ; }, abstract = {Descurainia sophia L. is one of the most problematic broad-leaf weed infesting winter wheat in China, and have evolved resistance to acetolactate synthase (ALS)-inhibiting herbicide of tribenuron-methyl. At least four ALS isozymes (ALS1 ∼ ALS4) exist in D. sophia, but these four ALS isozymes are not present in all D. sophia. In addition, amino acid mutations in ALS are mainly responsible for D. sophia resistance to tribenuron-methyl. In this study, D. sophia populations carrying homozygous mutation of Pro197Ser/Thr/Leu/Ala/His in ALS1 or in ALS2 were purified, respectively. Resistant D. sophia populations carrying mutant ALS exhibited 17 ∼ 694 folds resistance to tribenuorn-methyl. In addition, tribenuron-methyl resistance in D. sophia carrying ALS1 mutation was about 2.3 ∼ 11.4 folds higher than D. sophia with the same mutation in ALS2. The reduced binding affinity of ALS to tribenuron-methyl was mainly responsible for D. sophia resistance to tribenuron-methyl. However, the increase in resistance of D. sophia was not linear with the decrease of binding affinity of ALS to tribenuron-methyl. These results indicate that the effects of resistance mutations on ALS1 and ALS2 isozymes are not the same, and the ALS1 and ALS2 function differently in resistance evolution of D. sophia to tribenuron-methyl.}, } @article {pmid40015643, year = {2025}, author = {Hasumi, M and Ito, H and Machida, K and Niwa, T and Taminato, T and Nagai, Y and Imataka, H and Taguchi, H}, title = {Dissecting the mechanism of NOP56 GGCCUG repeat-associated non-AUG translation using cell-free translation systems.}, journal = {The Journal of biological chemistry}, volume = {301}, number = {4}, pages = {108360}, pmid = {40015643}, issn = {1083-351X}, mesh = {Humans ; Cell-Free System ; *Protein Biosynthesis ; *Nuclear Proteins/genetics/metabolism ; Introns ; Spinocerebellar Ataxias/genetics/metabolism ; Codon, Initiator/genetics ; *RNA, Small Nucleolar/genetics/metabolism ; *Trinucleotide Repeat Expansion ; }, abstract = {The repeat expansion in the human genome contributes to neurodegenerative disorders such as spinocerebellar ataxia (SCA) and amyotrophic lateral sclerosis. Transcripts with repeat expansions undergo noncanonical translation called repeat-associated non-AUG (RAN) translation. The NOP56 gene, implicated in SCA36, contains a GGCCTG repeat in its first intron. In tissues of patients with SCA36, poly (Gly-Pro) and poly (Pro-Arg) peptides, likely produced through NOP56 RAN translation in (NOP56-RAN), have been detected. However, the detailed mechanism underlying NOP56-RAN remains unclear. To address this, we used cell-free translation systems to investigate the mechanism of NOP56-RAN and identified the following features. (i) Translation occurs in all reading frames of the sense strand of NOP56 intron 1. (ii) Translation is initiated in a 5' cap-dependent manner from near-cognate start codons upstream of the GGCCUG repeat in each frame. (iii) Longer GGCCUG repeats enhance NOP56-RAN. (iv) A frameshift occurs within the GGCCUG repeat. These findings provide insights into the similarities between NOP56-RAN and other types of RAN translation.}, } @article {pmid40015332, year = {2025}, author = {Tavares de Sousa, M and Hergert, B and Crispi, F and Gomez, O and Hecher, K}, title = {Imaging the fetal aortic arch and its branching pattern in a midtrimester screening population.}, journal = {Ultraschall in der Medizin (Stuttgart, Germany : 1980)}, volume = {}, number = {}, pages = {}, doi = {10.1055/a-2548-2411}, pmid = {40015332}, issn = {1438-8782}, abstract = {UNLABELLED: Purpose Variants of the aortic arch branching have recently been found to have an impact for neonates undergoing surgical interventions of the thoracic aorta such as repair of aortic coarctation. They have been described prenatally in 6%, whereas they occur in up to 26% postnatally. To explore whether the branching variations might have been under-diagnosed in utero, we comprehensively assessed the aortic arch and its branching patterns in a low-risk population between 19 and 22 weeks of gestation. Material and Methods This prospective cohort study included 139 low-risk singleton pregnancies. During a standardized fetal echocardiography we investigated the aortic arch in a sagittal view according to predefined landmarks. Based on video clips, its branching pattern was categorized in normal branching or branching variants by two operators who were blinded to each other. Results Classification of the aortic arch branching was achieved in 127/139 (91.4%) cases. 103 cases (81.1%) showed a normal pattern and 24 cases (18.9%) a branching variant. Both operators agreed on 18 brachiobicephalic trunks "(THE SO CALLED BOVINE ARCH)": , 4 aberrant left vertebral arteries, one aortic arch with five branching vessels and in one case there was disagreement on the type of the variant. Conclusion Prenatal targeted echocardiography could identify a 18.9% prevalence of aortic arch branching variants in a low-risk population. Future studies are warranted to assess the clinical impact of our findings on neonates with congenital heart defects.

HINTERGRUND: Gefäßvarianten der thorakalen Aortenabgänge wurden als Risikofaktoren für Neugeborene identifiziert, die eine Intervention der Aorta, zum Beispiel bei Aortenisthmusstenose, vor sich haben. Pränatal wurde die Häufigkeit mit bis zu 6% beschrieben, während sie postnatal in bis zu 26% gefunden wurden. Um zu untersuchen, ob die Varianten bisher in utero unterdiagnostiziert wurden, untersuchten wir den Aortenbogen und die Abgänge in einer Niedrigrisikogruppe zwischen 19 und 22 Schwangerschaftswochen.

MATERIAL UND METHODEN: Diese prospektive Kohortenstudie umfasste 139 Einlingsschwangerschaften mit niedrigem Risiko. Während einer standardisierten fetalen Echokardiografie untersuchten wir den Aortenbogen in sagittaler Ebene. Anhand von Videoclips wurden die Abgänge des Aorta von zwei Untersuchenden, die zueinander verblindet waren, entweder als normales Abgangsmuster oder als Variante klassifiziert.

ERGEBNISSE: Die Klassifizierung des Abgänge der fetalen Aorta gelang in 127/139 (91,4 %) der Fälle. In 103 Fällen (81,1 %) wurde ein normales Abgangsmuster beobachtet, während in 24 Fällen (18,9 %) eine Variante vorlag. In 18 Fällen wurde ein Truncus brachiocephalicus (SOGENANNTER BOVINER AORTENBOGEN),: in 4 Fällen eine aberrante linke Vertebralarterie und in einem Fall ein Aortenbogen mit fünf abgehenden Gefäßen gefunden. In einem Fall waren die Untersuchenden bezüglich der Variante uneinig.

SCHLUSSFOLGERUNG: Die gezielte pränatale Echokardiografie konnte in einer Niedrigrisikopopulation eine Prävalenz von 18,9 % für Varianten der Abgänge des Aortenbogen identifizieren. Zukünftige Studien sind erforderlich, um die klinischen Auswirkungen unserer Ergebnisse auf Neugeborene mit angeborenen Herzfehlern zu bewerten.}, } @article {pmid40014834, year = {2025}, author = {Gusovsky Chevalier, AV and Lin, CC and Kerber, K and Reynolds, EL and Callaghan, BC and Burke, JF}, title = {Cost Trends of New-To-Market Neurologic Medications: An Insurance Claims Database Analysis.}, journal = {Neurology}, volume = {104}, number = {6}, pages = {e213428}, pmid = {40014834}, issn = {1526-632X}, support = {T32 HS029590/HS/AHRQ HHS/United States ; }, mesh = {Humans ; Male ; Female ; Databases, Factual ; United States ; *Nervous System Diseases/drug therapy/economics ; Middle Aged ; Aged ; Adult ; *Drug Costs/trends ; Migraine Disorders/drug therapy/economics ; Insurance Claim Review ; Young Adult ; }, abstract = {BACKGROUND AND OBJECTIVES: Costs for neurologic medications have increased considerably in recent years. Since 2014, more than 30 neurologic medications have been approved by the US Food and Drug Administration (FDA) for neurologic conditions. This study aims to characterize recent trends in annual costs and aggregate spending from 2012 to 2021 for new-to-market (NTM) medications for 9 neurologic conditions.

METHODS: We used the Merative MarketScan commercial and Medicare supplemental databases to observe patients seen by a neurologist with neurologic diseases with newly FDA-approved medications from 2014 to 2021: amyotrophic lateral sclerosis (ALS), transthyretin amyloidosis (ATTR), Duchenne muscular dystrophy (DMD), Huntington disease (HD), myasthenia gravis (MG), migraine, orthostatic hypotension (OH), tardive dyskinesia (TD), and spinal muscular atrophy (SMA). Patients were included if they had ≥1 disease-related prescription medication fill from 2012 to 2021. NTM (medications approved from 2014 to 2021) and older evidence-based guideline-supported medications were observed annually. Outcomes examined were annual and aggregate out-of-pocket (OOP) and total medication costs.

RESULTS: We identified 2,687 unique individuals with ALS, 38 with ATTR, 69 with DMD, 884 with HD, 9,984 with MG, 441,099 with migraine, 4,723 with OH, 1,266 with TD, and 17 with SMA. The youngest population was DMD (mean = 25 years [SD = 7]), and the oldest was TD (mean = 66 years [SD = 14]). For DMD, the population was 99% male and for migraine, the population was 84% female, and the other conditions had more relatively even sex divides. Collectively, migraine medications had the largest increase in aggregate costs (1993%) and had a substantial increase in OOP costs on average by 234% ($86-$288). Eculizumab for MG was an extreme outlier, with OOP costs increasing by 4,099% ($413-$17,359) and aggregate OOP costs by 7,005% ($5,375-$381,894). OOP costs of edaravone ($304-$5,707) and deutetrabenazine ($670-$7,170) sharply increased by 1,775% and 971%, respectively.

DISCUSSION: NTM medications for neurologic conditions have substantial and increasing individual and societal costs, which was not observed for older generic medications. These data suggest a need for policies to limit the financial burden of NTM medications on patients with neurologic conditions.}, } @article {pmid40013906, year = {2025}, author = {Howard, J and Bekker, HL and McDermott, CJ and McNeill, A}, title = {Exploring the needs and preferences of people with amyotrophic lateral sclerosis (ALS) when making genomic testing decisions: an interview study.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {26}, number = {5-6}, pages = {436-443}, doi = {10.1080/21678421.2025.2469727}, pmid = {40013906}, issn = {2167-9223}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/psychology/diagnosis ; Male ; Female ; Middle Aged ; *Genetic Testing/methods ; Aged ; *Decision Making ; *Patient Preference/psychology ; Adult ; Whole Genome Sequencing ; Interviews as Topic ; Genetic Counseling/psychology ; United Kingdom ; }, abstract = {Objective: Whole Genome Sequencing (WGS) for amyotrophic lateral sclerosis (ALS) (also known as motor neuron disease, MND) raises multiple considerations and has a range of implications for individuals and their family. However, it is unclear what needs people with ALS have when making genomic testing decisions. This study explores the experiences, needs and preferences of these individuals when considering WGS and going through the process. Methods: A semi-structured interview study was carried out with 14 people with ALS from across the UK who had, or were considering, WGS. Participants were recruited from a local ALS care center and MND Association/MND Scotland channels. Data were analyzed using framework analysis. Results: Findings indicate variation in (a) how WGS and access to pretest genetic counseling is provided, (b) the perceived adequacy of information to support decision-making and prepare people with ALS for their test result and its consequences, and (c) preferences for making decisions with family and health professionals that best meets their clinical and life needs along the care pathway. Conclusions: There is an urgent need for people with ALS to have relevant, accurate and accessible information that supports proactively their decision-making around WGS, particularly in the context of genetically-targeted treatments and clinical trials. These findings will contribute to the development of a shared decision-making intervention supporting people with ALS to make genomic testing decisions with their family and neurology services.}, } @article {pmid40012994, year = {2025}, author = {Sabetta, E and Ferrari, D and Massimo, L and Kõks, S}, title = {Tandem repeat expansions and copy number variations as risk factors and diagnostic tools for amyotrophic lateral sclerosis.}, journal = {Frontiers in neurology}, volume = {16}, number = {}, pages = {1522445}, pmid = {40012994}, issn = {1664-2295}, abstract = {Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disorder leading to upper and lower motoneurons degeneration. Although several mechanisms potentially involved in disease development have been identified, its pathogenesis is not fully understood. From the patient side, ALS diagnosis, still based on clinical criteria, can be difficult and may take up to 1 year. More than 30 genes have been associated to genetically inherited ALS, among which four (C9ORF72, SOD1, TARDBP and FUS) would explain around 60-70% of cases. However, familial ALS represents only 5-10% of ALS cases while the remaining are sporadic, with genetics explaining 6-10% of such cases only. In this context, short tandem repeats (STRs) expansions, have recently been found in clinically diagnosed ALS patients. In this review, we discuss the recent discoveries on ALS associated STRs and their potential as biomarkers as well as prognosis and therapy targets.}, } @article {pmid40012862, year = {2024}, author = {Tang, MB and Liu, YX and Hu, ZW and Luo, HY and Zhang, S and Shi, CH and Xu, YM}, title = {Study insights in the role of PGC-1α in neurological diseases: mechanisms and therapeutic potential.}, journal = {Frontiers in aging neuroscience}, volume = {16}, number = {}, pages = {1454735}, pmid = {40012862}, issn = {1663-4365}, abstract = {Peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), which is highly expressed in the central nervous system, is known to be involved in the regulation of mitochondrial biosynthesis, metabolic regulation, neuroinflammation, autophagy, and oxidative stress. This knowledge indicates a potential role of PGC-1α in a wide range of functions associated with neurological diseases. There is emerging evidence indicating a protective role of PGC-1α in the pathogenesis of several neurological diseases. As such, a deeper and broader understanding of PGC-1α and its role in neurological diseases is urgently needed. The present review provides a relatively complete overview of the current knowledge on PGC-1α, including its functions in different types of neurons, basic structural characteristics, and its interacting transcription factors. Furthermore, we present the role of PGC-1α in the pathogenesis of various neurological diseases, such as intracerebral hemorrhage, ischemic stroke, Alzheimer's disease, Parkinson's disease, Amyotrophic lateral sclerosis, Huntington's disease, and other PolyQ diseases. Importantly, we discuss some compounds or drug-targeting strategies that have been studied to ameliorate the pathology of these neurological diseases and introduce the possible mechanistic pathways. Based on the available studies, we propose that targeting PGC-1α could serve as a promising novel therapeutic strategy for one or more neurological diseases.}, } @article {pmid40012679, year = {2025}, author = {Glashutter, M and Wijesinghe, P and Matsubara, JA}, title = {TDP-43 as a potential retinal biomarker for neurodegenerative diseases.}, journal = {Frontiers in neuroscience}, volume = {19}, number = {}, pages = {1533045}, pmid = {40012679}, issn = {1662-4548}, abstract = {TDP-43 proteinopathies are a spectrum of neurodegenerative diseases (NDDs) characterized by the pathological cytoplasmic aggregation of the TDP-43 protein. These include amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration (FTLD), Alzheimer's disease (AD), chronic traumatic encephalopathy (CTE), and others. TDP-43 in the eye shows promise as a biomarker for these NDDs. Several studies have identified cytoplasmic TDP-43 inclusions in retinal layers of donors with ALS, FTLD, AD, CTE, and other conditions using immunohistochemistry. Our findings suggest that pathological aggregates of TDP-43 in the human retina are most prevalent in FTLD-TDP, ALS, and CTE, suggesting these diseases may provide the most reliable context for studying the potential of TDP-43 as a retinal biomarker. Animal model studies have been pivotal in exploring TDP-43's roles in the retina, including its nuclear and cytoplasmic localization, RNA binding properties, and interactions with other proteins. Despite these advances, more research is needed to develop therapeutic strategies. A major limitation of human autopsy studies is the lack of corresponding brain pathology assessments to confirm TDP-43 proteinopathy diagnosis and staging. Other limitations include small sample sizes, lack of antemortem eye pathology and clinical histories, and limited comparisons across multiple NDDs. Future directions for the TDP-43 as a retinal biomarker for NDDs include retinal tracers, hyperspectral imaging, oculomics, and machine learning development.}, } @article {pmid40012394, year = {2025}, author = {Kumar, P and Kumar, A and Keerthipriya, M and H, C and Nalini, A and Vengalil, S and Sitani, K and Nagaraj, C and Dey, S and Debnath, M and K, V and Sathyaprabha, TN}, title = {A New Approach to Synthesize Carbon-11-PBR28 and its Clinical Validation in ALS Patients.}, journal = {Current radiopharmaceuticals}, volume = {18}, number = {3}, pages = {216-223}, pmid = {40012394}, issn = {1874-4729}, support = {5/4-5/184/Neuro/CAR-Phase-II/2018-NCD-I//Indian Council of Medical Research (ICMR)/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/diagnostic imaging ; Humans ; *Carbon Radioisotopes/chemistry ; *Radiopharmaceuticals/chemical synthesis ; Positron-Emission Tomography/methods ; Male ; Middle Aged ; Female ; Magnetic Resonance Imaging ; Aged ; Receptors, GABA/metabolism ; Chromatography, High Pressure Liquid ; *Pyridines/chemical synthesis ; }, abstract = {INTRODUCTION: Many studies have reported translocator protein (TSPO) overexpression in various neurological disorders. Carbon-11[[11]C]PBR28 is a widely used TSPO Positron Emission Tomography (PET) radiopharmaceutical. We compared HPLC-based purification with cartridge-based purification and performed PET-MR imaging in ALS patients.

METHODS: [[11]C]PBR28 was synthesized using both an HPLC-based and cartridge-based purification technique on the FX2C chemistry module. We injected 350 ± 20 MBq of the [[11]C]PBR28 intravenously into the patients diagnosed with amyotrophic lateral syndrome (ALS) limb onset (n =3) and bulbar (n =3). Simultaneous PET-MR dynamic imaging was then performed.

RESULTS: The radiochemical purity exceeded 95% with both methods. Using the HPLC-based method, the radiochemical yield was 11.8 ± 3.3%, molar activity was 253 ± 20.9 GBq/μmol, and the total synthesis time of 25 ± 2 minutes. In contrast, the cartridge-based method yielded a radiochemical yield of 53.0 ± 3.6%, a molar activity of 885 ± 17.7 GBq/μmol, and a total synthesis time of 12 ± 2 minutes. In imaging results, higher activity was observed in the precentral gyrus and cerebellum at 2.5 ± 0.5 minutes in bulbar-onset ALS cases, with a standardized uptake value (SUV) of 2.3 ± 0.3. In contrast, limb-onset ALS cases showed the highest uptake at 0.5 ± 0.2 minutes, with an SUV of 1.5 ± 0.2.

DISCUSSION: The difference in SUV in bulbar and limb onset may be due to pathological changes.

CONCLUSION: The cartridge-based purification method provided higher radiochemical yield and molar activity as compared to the HPLC purification method.}, } @article {pmid40012174, year = {2025}, author = {Rajamanickam, G and Hu, Z and Liao, P}, title = {Targeting the TRPM4 Channel for Neurologic Diseases: Opportunity and Challenge.}, journal = {The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry}, volume = {}, number = {}, pages = {10738584251318979}, doi = {10.1177/10738584251318979}, pmid = {40012174}, issn = {1089-4098}, abstract = {As a monovalent cation channel, the transient receptor potential melastatin 4 (TRPM4) channel is a unique member of the transient receptor potential family. Abnormal TRPM4 activity has been identified in various neurologic disorders, such as stroke, spinal cord injury, traumatic brain injury, multiple sclerosis, amyotrophic lateral sclerosis, pathologic pain, and epilepsy. Following brain hypoxia/ischemia and inflammation, TRPM4 up-regulation and enhanced activity contribute to the cell death of neurons, vascular endothelial cells, and astrocytes. Enhanced ionic influx via TRPM4 leads to cell volume increase and oncosis. Depolarization of membrane potential following TRPM4 activation and interaction between TRPM4 and N-methyl-d-aspartate receptors exacerbate excitotoxicity during hypoxia. Importantly, TRPM4 expression and activity remain low in healthy neurons, making it an ideal drug target. Current approaches to inhibit or modulate the TRPM4 channel have various limitations that hamper the interpretation of TRPM4 physiology in the nervous system and potentially hinder their translation into therapy. In this review, we discuss the pathophysiologic roles of TRPM4 and the different inhibitors that modulate TRPM4 activity for potential treatment of neurologic diseases.}, } @article {pmid40011745, year = {2025}, author = {Rödström, KEJ and Eymsh, B and Proks, P and Hayre, MS and Cordeiro, S and Mendez-Otalvaro, E and Madry, C and Rowland, A and Kopec, W and Newstead, S and Baukrowitz, T and Schewe, M and Tucker, SJ}, title = {Cryo-EM structure of the human THIK-1 K2P K[+] channel reveals a lower Y gate regulated by lipids and anesthetics.}, journal = {Nature structural & molecular biology}, volume = {32}, number = {7}, pages = {1167-1174}, pmid = {40011745}, issn = {1545-9985}, support = {/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Humans ; Cryoelectron Microscopy ; *Potassium Channels, Tandem Pore Domain/chemistry/metabolism/ultrastructure/genetics ; Halothane/pharmacology/chemistry ; Models, Molecular ; Binding Sites ; Ion Channel Gating/drug effects ; *Anesthetics/pharmacology ; Protein Conformation ; }, abstract = {THIK-1 (KCNK13) is a halothane-inhibited and anionic-lipid-activated two-pore domain (K2P) K[+] channel implicated in microglial activation and neuroinflammation, and a current target for the treatment of neurodegenerative disorders, for example Alzheimer's disease and amyothropic lateral sclerosis (ALS). However, compared to other K2P channels, little is known about the structural and functional properties of THIK-1. Here we present a 3.16-Å-resolution cryo-EM structure of human THIK-1 that reveals several distinct features, in particular, a tyrosine in M4 that contributes to a lower 'Y gate' that opens upon activation by physiologically relevant G-protein-coupled receptor and lipid signaling pathways. We demonstrate that linoleic acid bound within a modulatory pocket adjacent to the filter influences channel activity, and that halothane inhibition involves a binding site within the inner cavity, both resulting in conformational changes to the Y gate. Finally, the extracellular cap domain contains positively charged residues that line the ion exit pathway and contribute to the distinct biophysical properties of this channel. Overall, our results provide structural insights into THIK-1 function and identify distinct regulatory sites that expand its potential as a drug target for the modulation of microglial function.}, } @article {pmid40011708, year = {2025}, author = {Yang, C and Lee, GB and Hao, L and Hu, F}, title = {TMEM106B deficiency leads to alterations in lipid metabolism and obesity in the TDP-43[Q331K] knock-in mouse model.}, journal = {Communications biology}, volume = {8}, number = {1}, pages = {315}, pmid = {40011708}, issn = {2399-3642}, support = {R01 NS088448/NS/NINDS NIH HHS/United States ; R21 AG078741/AG/NIA NIH HHS/United States ; R01NS088448//U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; R01 NS121608/NS/NINDS NIH HHS/United States ; R21AG078741//U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ ; R01NS121608//U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; }, mesh = {Animals ; *Lipid Metabolism/genetics ; Mice ; *Membrane Proteins/genetics/deficiency/metabolism ; *Obesity/genetics/metabolism ; *DNA-Binding Proteins/genetics/metabolism ; Disease Models, Animal ; Gene Knock-In Techniques ; *Nerve Tissue Proteins/genetics/deficiency/metabolism ; Male ; Liver/metabolism ; Mice, Knockout ; *TDP-43 Proteinopathies/genetics/metabolism ; }, abstract = {The TMEM106B gene, encoding a lysosomal membrane protein, is closely linked with brain aging and neurodegeneration. TMEM106B has been identified as a risk factor for several neurodegenerative diseases characterized by aggregation of the RNA-binding protein TDP-43, including frontotemporal lobar degeneration (FTLD) and limbic-predominant age-related TDP-43 encephalopathy (LATE). To investigate the role of TMEM106B in TDP-43 proteinopathy, we ablated TMEM106B in the TDP-43[Q331K] knock-in mouse line, which expresses an ALS-linked TDP-43 mutation at endogenous levels. We found that TMEM106B deficiency leads to glial activation, Purkinje cell loss, and behavioral deficits in TDP-43[Q331K] mice without inducing typical TDP-43 pathology. Interestingly, ablation of TMEM106B results in significant body weight gain, increased fat deposition, and hepatic triglyceride (TG) accumulation in TDP-43[Q331K] mice. In addition, lipidomic and transcriptome analysis shows a profound alteration in lipid metabolism in the liver of TDP-43[Q331K]Tmem106b[-/-] mice. Our studies reveal a novel function of TMEM106B and TDP-43 in lipid metabolism and provide new insights into their roles in neurodegeneration.}, } @article {pmid40011434, year = {2025}, author = {Gao, G and Shi, Y and Deng, HX and Krainc, D}, title = {Dysregulation of mitochondrial α-ketoglutarate dehydrogenase leads to elevated lipid peroxidation in CHCHD2-linked Parkinson's disease models.}, journal = {Nature communications}, volume = {16}, number = {1}, pages = {1982}, pmid = {40011434}, issn = {2041-1723}, support = {R21 NS114765/NS/NINDS NIH HHS/United States ; NS114765//U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; R01 NS099623/NS/NINDS NIH HHS/United States ; R35 NS122257/NS/NINDS NIH HHS/United States ; NS122257//U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; NS099623//U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; }, mesh = {Animals ; *Mitochondria/metabolism/enzymology ; *Ketoglutarate Dehydrogenase Complex/metabolism/genetics ; Humans ; *Lipid Peroxidation/drug effects ; *Parkinson Disease/metabolism/genetics/pathology ; Male ; Mice ; Disease Models, Animal ; alpha-Synuclein/metabolism ; Dopaminergic Neurons/metabolism/drug effects ; *Transcription Factors/genetics/metabolism ; Mice, Knockout ; Thioctic Acid/pharmacology ; DNA-Binding Proteins/metabolism/genetics ; Brain/metabolism ; *Mitochondrial Proteins/metabolism/genetics ; Ketoglutaric Acids/metabolism ; Mice, Inbred C57BL ; }, abstract = {Dysregulation of mitochondrial function has been implicated in Parkinson's disease (PD), but the role of mitochondrial metabolism in disease pathogenesis remains to be elucidated. Using an unbiased metabolomic analysis of purified mitochondria, we identified alterations in α-ketoglutarate dehydrogenase (KGDH) pathway upon loss of PD-linked CHCHD2 protein. KGDH, a rate-limiting enzyme complex in the tricarboxylic acid cycle, was decreased in CHCHD2-deficient male mouse brains and human dopaminergic neurons. This deficiency of KGDH led to elevated α-ketoglutarate and increased lipid peroxidation. Treatment of CHCHD2-deficient dopaminergic neurons with lipoic acid, a KGDH cofactor and antioxidant agent, resulted in decreased levels of lipid peroxidation and phosphorylated α-synuclein. CHCHD10, a close homolog of CHCHD2 that is primarily linked to amyotrophic lateral sclerosis/frontotemporal dementia, did not affect the KGDH pathway or lipid peroxidation. Together, these results identify KGDH metabolic pathway as a targetable mitochondrial mechanism for correction of increased lipid peroxidation and α-synuclein in Parkinson's disease.}, } @article {pmid40010009, year = {2025}, author = {Mikuriya, S and Takegawa-Araki, T and Tamura, M}, title = {Edaravone mitigates TDP-43 mislocalization in human amyotrophic lateral sclerosis neurons with potential implication of the SIRT1-XBP1 pathway.}, journal = {Free radical biology & medicine}, volume = {230}, number = {}, pages = {283-293}, doi = {10.1016/j.freeradbiomed.2025.01.012}, pmid = {40010009}, issn = {1873-4596}, mesh = {*Edaravone/pharmacology ; Humans ; *Amyotrophic Lateral Sclerosis/drug therapy/genetics/pathology/metabolism ; *DNA-Binding Proteins/genetics/metabolism ; *X-Box Binding Protein 1/genetics/metabolism ; *Motor Neurons/drug effects/metabolism/pathology ; Induced Pluripotent Stem Cells/drug effects/metabolism ; *Sirtuin 1/metabolism/genetics ; Endoplasmic Reticulum Stress/drug effects ; Signal Transduction/drug effects ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by progressive motor neuron loss along with pathological mislocalization of TAR DNA-binding protein 43 (TDP-43), a protein implicated in RNA metabolism. Although edaravone, a free-radical scavenger, has been approved for ALS treatment, its precise mechanism of action is not fully understood, particularly in relation to TDP-43 pathology. Here, we investigated the effects of edaravone on induced pluripotent stem cell (iPSC)-derived motor neurons in a patient with ALS harboring a TDP-43 mutation. Our results demonstrated that edaravone significantly attenuated neurodegeneration, as evidenced by neurite preservation, neuronal cell death reduction, and correction of aberrant cytoplasmic localization of TDP-43. These neuroprotective effects were not observed with vitamin C, indicating a unique mechanism of action for edaravone, distinct from its antioxidative properties. RNA sequencing revealed that edaravone rapidly modulated gene expression, including protein quality control pathway, such as the ubiquitin-proteasome system. Further analysis identified X-box binding protein (XBP1), a key regulator of the endoplasmic reticulum stress response, as a critical factor in the therapeutic effects of edaravone. This study suggests that edaravone may offer a multifaceted therapeutic approach for ALS by targeting oxidative stress and TDP-43 mislocalization through distinct molecular pathways.}, } @article {pmid40009859, year = {2025}, author = {Chung, J and Lim, F}, title = {Effect of Nurse Residency Programs on New Graduate Nurses Entering the Critical Care Setting: An Integrative Review.}, journal = {Critical care nursing quarterly}, volume = {48}, number = {2}, pages = {120-142}, pmid = {40009859}, issn = {1550-5111}, mesh = {Humans ; *Clinical Competence ; Preceptorship ; *Critical Care Nursing/education ; *Internship, Nonmedical ; *Critical Care ; }, abstract = {The transition period from undergraduate nursing education to professional practice is a time of uncertainty and great difficulty for new graduate nurses (NGNs). Nurse residency programs (NRPs) provide structured education, simulation-based learning, and preceptorship to ease the transition. Although its effect on improving retention of NGNs is well established in the literature, the effect on clinical competency has not been documented as well. The purpose of this integrative review is to appraise the available literature and synthesize the evidence that demonstrates the effect of NRPs on clinical competency of NGNs entering the critical care setting. Inclusion criteria were quantitative and qualitative studies, peer-reviewed studies published after 2004 and in English, identified through a systematic literature search using the CINAHL database. Critical appraisal of the articles was completed using Law et al's Critical Review Form. Eight articles (4 quantitative, 3 mixed method, and 1 qualitative study) met the inclusion criteria. The themes identified were common tools used to assess the efficacy of NRPs, improved clinical competency of NGNs, improved self-confidence, improved retention rates, and peer support among NGNs. Implications for nursing education and practice include applying evidence-based NRPs, incorporating simulation, enhancing sustainability, and reducing NRP variability through accreditation.}, } @article {pmid40009787, year = {2025}, author = {Mondesert, E and Delaby, C and De La Cruz, E and Kuhle, J and Benkert, P and Pradeilles, N and Duchiron, M and Morchikh, M and Camu, W and Cristol, JP and Hirtz, C and Esselin, F and Lehmann, S}, title = {Comparative Performances of 4 Serum NfL Assays, pTau181, and GFAP in Patients With Amyotrophic Lateral Sclerosis.}, journal = {Neurology}, volume = {104}, number = {6}, pages = {e213400}, pmid = {40009787}, issn = {1526-632X}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/blood/diagnosis/mortality ; Female ; Male ; *Neurofilament Proteins/blood ; Aged ; *tau Proteins/blood ; Middle Aged ; *Glial Fibrillary Acidic Protein/blood ; Biomarkers/blood ; Cohort Studies ; Prognosis ; Phosphorylation ; }, abstract = {BACKGROUND AND OBJECTIVES: Selecting the most appropriate blood tests is crucial for the management of patients with amyotrophic lateral sclerosis (ALS). This study evaluates the diagnostic and prognostic performance of neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), and phosphorylated tau 181 (pTau181) biomarkers in ALS to establish their clinical relevance and cutoff values.

METHODS: In a cohort of patients from the ALS center in Montpellier, we conducted a head-to-head comparison of 4 different technologies and 3 distinct serum analytes: NfL was tested using the ultrasensitive Simoa and the microfluidic Ella platforms, along with 2 assays recently set up on clinical-grade platforms: Lumipulse and Elecsys. We also used Elecsys to assess serum GFAP and pTau181.

RESULTS: Our cohort included 139 patients with ALS and 70 non-ALS patients, with a mean age of 66.1 ± 11.4 years and 47.4% of women. The mean follow-up was 42 ± 26.3 months for patients with ALS and 141.6 ± 106.3 months for non-ALS patients, with a mortality rate of 85.5% vs 7.7%. There was a high correlation between all methods tested for serum NfL quantification (R[2] = 0.939 to 0.963). The area under the curve (AUC) for ALS diagnosis was 0.889 (0.827-0.932) for NfL Simoa, 0.906 (0.847-0.944) for Ella, 0.912 (0.853-0.948) for Lumipulse, and 0.910 (0.851-0.946) for Elecsys. Serum pTau181 and GFAP showed poor diagnostic performance with AUCs of 0.565 (0.472-0.649) and 0.546 (0.461-0.636), respectively. Kaplan-Meier survival analysis revealed significant hazard ratios (4.4-5.4) for blood NfL. Patients with ALS had a 40%-50% chance of surviving 50 weeks below the prognostic cutoff values while survival rates dropped to near zero above. NfL and GFAP levels were associated with age and body mass index, considered confounding factors. pTau181 levels varied significantly in patients with ALS depending on the site of onset.

DISCUSSION: This study demonstrates the consistent performance of 4 immunoassays for serum NfL quantification in ALS. NfL showed high diagnostic and prognostic accuracy, making it suitable for individual assessment, unlike GFAP or pTau181. We propose diagnostic and prognostic cutoff values for serum NfL, providing a basis for wider implementation, especially with the clinically accredited Lumipulse and Elecsys platforms, which are becoming standard practice.

CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that serum NfL levels are useful in identifying over 80% of patients with ALS and predicting survival in patients with ALS compared with pTau181 and GFAP levels.}, } @article {pmid40009417, year = {2025}, author = {Oliveira Santos, M and Pinto, S and Silveira, F and Gromicho, M and Alves, I and Castro, J and Castro, I and de Carvalho, M}, title = {Amyotrophic Lateral Sclerosis Associated With Severe Sensory Neuronopathy: Case Series.}, journal = {Journal of clinical neuromuscular disease}, volume = {26}, number = {3}, pages = {133-139}, doi = {10.1097/CND.0000000000000520}, pmid = {40009417}, issn = {1537-1611}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/complications/physiopathology ; Male ; Middle Aged ; Female ; Aged ; Disease Progression ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder affecting primarily the motor system. However, an association with sensory neuronopathy has been scarcely described. We described 3 unrelated patients (2 males) with sporadic spinal-onset ALS and sensory neuronopathy. Mean onset age was 63.7 years and mean Revised Amyotrophic Lateral Sclerosis Functional Rating Scale at diagnosis was 42. Sensory disturbances emerged before or overlap with motor symptoms in the same onset region and followed the same pattern of lower motor neuron involvement over disease progression. Two patients have also bilateral trigeminal sensory fibers affection. None had cognitive abnormalities. Genetic testing for the most common ALS-associated genes was unrevealing. Mean disease duration and ALS functional rating scale-revised at last visit was 47 months and 27, respectively. One patient is still alive, dependent on nocturnal noninvasive ventilation. Motor neuron disease is now considered a multisystem neurodegenerative disorder, and sensory neuronopathy, although very rare, should not be neglected as a possible part of the disease spectrum.}, } @article {pmid40009414, year = {2025}, author = {Hamad, AA}, title = {Tofersen for Amyotrophic Lateral Sclerosis: Genetic Treatment With Precision Medicine: The Future of ALS Treatment.}, journal = {Journal of clinical neuromuscular disease}, volume = {26}, number = {3}, pages = {117-119}, doi = {10.1097/CND.0000000000000517}, pmid = {40009414}, issn = {1537-1611}, } @article {pmid40009412, year = {2025}, author = {Finsterer, J}, title = {Before Trapezius RNS Can Be Recommended as an Additional Tool for the Diagnosis of ALS, Well-Powered Prospective Studies Are Required.}, journal = {Journal of clinical neuromuscular disease}, volume = {26}, number = {3}, pages = {114-115}, doi = {10.1097/CND.0000000000000515}, pmid = {40009412}, issn = {1537-1611}, } @article {pmid40009238, year = {2025}, author = {Ruffo, P and Traynor, BJ and Conforti, FL}, title = {Advancements in genetic research and RNA therapy strategies for amyotrophic lateral sclerosis (ALS): current progress and future prospects.}, journal = {Journal of neurology}, volume = {272}, number = {3}, pages = {233}, pmid = {40009238}, issn = {1432-1459}, support = {ZIA AG000933/ImNIH/Intramural NIH HHS/United States ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/therapy ; *Genetic Therapy/methods/trends ; Animals ; }, abstract = {This review explores the intricate landscape of neurodegenerative disease research, focusing on Amyotrophic Lateral Sclerosis (ALS) and the intersection of genetics and RNA biology to investigate the causative pathogenetic basis of this fatal disease. ALS is a severe neurodegenerative disease characterized by the progressive loss of motor neurons, leading to muscle weakness and paralysis. Despite significant research advances, the exact cause of ALS remains largely unknown. Thanks to the application of next-generation sequencing (NGS) approaches, it was possible to highlight the fundamental role of rare variants with large effect sizes and involvement of portions of non-coding RNA, providing valuable information on risk prediction, diagnosis, and treatment of age-related diseases, such as ALS. Genetic research has provided valuable insights into the pathophysiology of ALS, leading to the development of targeted therapies such as antisense oligonucleotides (ASOs). Regulatory agencies in several countries are evaluating the commercialization of Qalsody (Tofersen) for SOD1-associated ALS, highlighting the potential of gene-targeted therapies. Furthermore, the emerging significance of microRNAs (miRNAs) and long RNAs are of great interest. MiRNAs have emerged as promising biomarkers for diagnosing ALS and monitoring disease progression. Understanding the role of lncRNAs in the pathogenesis of ALS opens new avenues for therapeutic intervention. However, challenges remain in delivering RNA-based therapeutics to the central nervous system. Advances in genetic screening and personalized medicine hold promise for improving the management of ALS. Ongoing clinical trials use genomic approaches for patient stratification and drug targeting. Further research into the role of non-coding RNAs in the pathogenesis of ALS and their potential as therapeutic targets is crucial to the development of effective treatments for this devastating disease.}, } @article {pmid40008462, year = {2025}, author = {Huertas-Alonso, AJ and González-Serrano, DJ and Salgado-Ramos, M and Hadidi, M and Sánchez-Verdú, P and Cabañas, B and Chuck, CJ and Clark, JH and Moreno, A}, title = {Sustainable Microwave-Assisted Synthesis of Medium- and Long-Chain Alkyl Levulinates from Biomass-Derived Levulinic Acid.}, journal = {ChemSusChem}, volume = {18}, number = {10}, pages = {e202402508}, pmid = {40008462}, issn = {1864-564X}, support = {SBPLY/17/180501/000522//Junta de Comunidades de Castilla-La Mancha/ ; RTI2018-099503-B-I00//Ministerio de Ciencia, Innovación y Universidades/ ; }, abstract = {Alkyl levulinates (ALs) represent a family of bio-compounds derived from levulinic acid (LA), a platform chemical obtained from lignocellulosic biomass. Medium- and long-chain ALs (pentyl levulinate or longer) have shown potential as biofuel and fuel additives due to their relatively low oxygen content and resemblance to biodiesel. This study reports a fast and environmentally friendly method for synthesizing ALs via microwave (MW)-assisted LA esterification, laying emphasis on medium- and long-chain ALs. By combining p-toluenesulfonic acid (5 wt % loading) as catalyst and MW radiation as heating source for a short time (5 minutes), excellent yields of ALs (≥89 mol %) were achieved for a wide range of primary and secondary alcohols (2-10 carbons), overcoming the expected lower reactivity of long chain alcohols. Additionally, formation of undesired side products, such as dialkyl ethers or LA aldol condensation products, was significantly minimized. The feasibility of recovering the unreacted alcohol was successfully proved by simple distillation (88 wt % recovery). The green chemistry metrics assessment proved that this approach aligns with the green chemistry principles and the United Nations Sustainable Development Goals, offering a more sustainable pathway for biofuel and fuel additive production.}, } @article {pmid40008327, year = {2025}, author = {van Eijk, RPA and Steyn, FJ and Janse van Mantgem, MR and Schmidt, A and Meyjes, M and Allen, S and Daygon, DV and Loeffler, JP and Al-Chalabi, A and van den Berg, LH and Henderson, RD and Ngo, ST}, title = {An open-label Phase 2a study to assess the safety and tolerability of trimetazidine in patients with amyotrophic lateral sclerosis.}, journal = {Brain communications}, volume = {7}, number = {1}, pages = {fcaf063}, pmid = {40008327}, issn = {2632-1297}, abstract = {Metabolic imbalance is associated with amyotrophic lateral sclerosis progression. Impaired glucose oxidation and increased reliance on fatty acid oxidation contribute to reduced metabolic flexibility and faster disease progression in amyotrophic lateral sclerosis. We sought to evaluate the safety and tolerability, and explore the pharmacodynamic response of trimetazidine, a partial fatty acid oxidation inhibitor, on oxidative stress markers and energy expenditure in amyotrophic lateral sclerosis. The study was conducted between June 29, 2021 and May 24, 2023. People living with amyotrophic lateral sclerosis, recruited in Australia and the Netherlands, received open-label oral trimetazidine for 12 weeks after an initial 4-week lead-in period. The primary outcome measures were safety and tolerability, as well as the change from baseline in oxidative stress markers malondialdehyde (MDA) and 8-hydroxy-2'-deoxyguanosine (8-OHdG). Secondary outcome measures were change from baseline in energy expenditure, amyotrophic lateral sclerosis functional rating scale-revised, and slow vital capacity (SVC). Linear mixed effects were used to estimate the mean difference in MDA and 8-OHdG between the on- and off-treatment periods. This trial is registered under ClinicalTrial.gov National Clinical Trial (NCT) number NCT04788745 and European Union Drug Regulating Authorities Clinical Trials (EudraCT) number 2020-005018-17. Twenty-one participants received trimetazidine; 19 (90%) completed the treatment period. Trimetazidine was well tolerated; there were 57 adverse events reported, of which 7 (11%) were deemed potentially drug-related, including hot flushes (2), nausea (2), paraesthesia (2) and fatigue (1). MDA was numerically lower during treatment [-0.29 uM; 95% confidence interval (CI) -0.90 to 0.33, P = 0.36]; 8-OHdG was significantly lower during treatment (-0.12 nM; 95% CI -0.23 to -0.01, P = 0.0245). The decrease in oxidative stress markers was accompanied by a reduction in resting energy expenditure (95 kcal, 95% CI 36.8-154, P = 0.0014). The absence of a placebo group prevented the interpretation of the clinical parameters. Oral trimetazidine was safe and well tolerated among patients with amyotrophic lateral sclerosis. This, combined with the significant reduction in markers of oxidative stress and resting energy expenditure, warrants a larger double-blind placebo-controlled efficacy study.}, } @article {pmid40008320, year = {2025}, author = {Wulterkens, D and Coumou, F and Slagt, C and Waalewijn, RA and Mommers, L}, title = {Defibrillation pad placement accuracy among Advanced Life Support instructors: A manikin-based observational study examining experience, self-evaluation, and actual performance.}, journal = {Resuscitation plus}, volume = {22}, number = {}, pages = {100886}, pmid = {40008320}, issn = {2666-5204}, abstract = {BACKGROUND: Ventricular fibrillation is common in patients with out-of-hospital cardiac arrest. Early and effective defibrillation is important for their survival. Effective defibrillation depends highly on correct positioning of the defibrillation pads. Teaching this correctly by ALS instructors is therefore crucial.

METHODS: Fifty certified advanced life support instructors were recruited from a large training institute. Participants were asked to place defibrillation pads on an anatomically and real-weight (90 kg) manikin. Primary outcome was the placement of defibrillation pads placed in the sternal-apical and anterior-posterior positions. Secondary outcomes were performance self-assessment, defibrillation experience, self-perceived competence and self-efficacy in teaching defibrillation. These measures were evaluated using an 11-point Likert scale.

RESULTS: A total of 31 medical doctors and 19 registered nurses were enrolled in this study. Defibrillation pads were placed (mean ± SD) 42 ± 21 mm, 38 ± 23 mm, 35 ± 19 mm and 61 ± 48 mm from the reference point for the sternal, apical, anterior and posterior pads respectively, resulting in a respectively correct placement of 18%, 20%, 32% and 28%. The average number of correctly applied pads per instructor was 0.98 ± 0.74 out of four.Self-assessment of defibrillation pads placed by the participants were 8.56 ± 1.33 and 7.88 ± 1.64 for the sternal-apical and anterior-posterior positions respectively. Personal defibrillation experience showed that the majority had applied over 20 standard defibrillations. Experience with anterior-posterior pad placement was less and experience with bi-axillary and double sequential external defibrillation positions were absent in most participants. Self-perceived competence for the sternal-apical, anterior-posterior, bi-axillary and dual external synchronized positions were 8.68 ± 1.06, 8.08 ± 1.37, 5.57 ± 2.95 and 5.11 ± 2.67 respectively. Self-efficacy score for teaching defibrillation was 8.59 ± 0.81. No association was found between the number of correctly applied pads and any of the participants' variables.

CONCLUSION: This study corroborates and expands upon existing knowledge regarding the challenges of defibrillator pad placement, revealing substantial variation in placement accuracy among instructors. Our novel analysis of pad angles and anterior-posterior analysis demonstrates that a significant portion of pads are incorrectly placed. These findings highlight the need for standardized approaches and improved training methodologies in defibrillator pad placement.}, } @article {pmid40008198, year = {2025}, author = {Garetto, B and Cao, N and Finelli, V and Aunan, E and Signorile, M and Olsbye, U and Bordiga, S and Nova, A and Borfecchia, E}, title = {Pinpointing Cu-Coordination Motifs in Bio-Inspired MOFs by Combining DFT-Assisted XAS Analysis and Multivariate Curve Resolution.}, journal = {The journal of physical chemistry. C, Nanomaterials and interfaces}, volume = {129}, number = {7}, pages = {3570-3582}, pmid = {40008198}, issn = {1932-7447}, abstract = {In recent years, X-ray absorption spectroscopy (XAS) has emerged as an essential technique for investigating the structure and composition of heterogeneous catalysts, providing valuable insights into the nature of active sites within these systems. However, the average nature of the XAS signal, inherently merged over all the absorber-containing species forming during in situ/operando experiments, often complicates the interpretation of the data. Nonetheless, advanced analysis methods have been developed to address this problem. In particular, herein we employed in situ XAS spectroscopy together with multivariate curve resolution-alternating least squares (MCR-ALS) and wavelet transform (WT) analysis to monitor the evolution of distinct Cu species in histidine-modified Cu-UiO-66 MOFs and to obtain detailed structural insights about the Cu sites. A novel approach adopted in this work was the application of density functional theory (DFT)-assisted extended X-ray absorption fine structure (EXAFS) fitting to quantitatively refine the local structure of the MCR-derived pure Cu species. This approach revealed the preferential redox activity of Cu[II] ions coordinated within the defective Zr clusters of the MOF, compared to Cu[II] ions bound to both the histidine molecule and the defective site during a standard redox reaction protocol.}, } @article {pmid40007904, year = {2025}, author = {Esteruelas, G and Ettcheto, M and Haro, I and Herrando-Grabulosa, M and Gaja-Capdevila, N and Gomara, MJ and Navarro, X and Espina, M and Souto, EB and Camins, A and García, ML and Sánchez-López, E}, title = {Novel Tissue-Specific Multifunctionalized Nanotechnological Platform Encapsulating Riluzole Against Motor Neuron Diseases.}, journal = {International journal of nanomedicine}, volume = {20}, number = {}, pages = {2273-2288}, pmid = {40007904}, issn = {1178-2013}, mesh = {*Riluzole/administration & dosage/pharmacokinetics/chemistry ; Animals ; *Nanoparticles/chemistry ; *Neuroprotective Agents/administration & dosage/pharmacokinetics/chemistry ; *Motor Neuron Disease/drug therapy ; Humans ; Motor Neurons/drug effects/metabolism ; Amyotrophic Lateral Sclerosis/drug therapy ; Drug Carriers/chemistry ; Mice ; Polyethylene Glycols/chemistry ; Drug Delivery Systems/methods ; Polylactic Acid-Polyglycolic Acid Copolymer/chemistry ; Blood-Brain Barrier/metabolism ; }, abstract = {BACKGROUND: Motor neuron diseases are neurological disorders characterized by progressive degeneration of upper and/or lower motor neurons. Amyotrophic Lateral Sclerosis (ALS) is the most common form of motor neuron diseases, where patients suffer progressive paralysis, muscle atrophy and finally death. Despite ALS severity, no treatment is safe and fully effective. In this area, Riluzole was the first drug approved and it constitutes the gold-standard for this pathology. However, to obtain suitable therapeutic efficacy, Riluzole requires high doses that are associated with severe adverse effects in other tissues. To attain Riluzole therapeutic efficacy avoiding other organs side-effects, new therapeutic strategies to enhance the delivery of Riluzole specifically to motor neurons constitute an unmet medical need. In this area, we have developed a novel multifunctional nanostructurated carrier to selectively deliver Riluzole to motor neurons.

RESULTS: This work develops and characterizes at in vitro and in vivo levels a tissue-targeted formulation of peptide and PEG-labelled PLGA nanoparticles encapsulating Riluzole. For this purpose, pVEC, a cell penetrating peptide able to increase transport through the blood-brain barrier, was attached to the nanoparticles surface. The multifunctionalized nanoparticles show suitable characteristics for the release of Riluzole in the central nervous system and were detected in motor neurons within 1 h after administration while significantly reducing the concentration of Riluzole in non-therapeutic organs responsible of side effects.

CONCLUSION: A novel drug delivery system has been developed and characterized, demonstrating enhanced CNS biodistribution of riluzole, which shows promise as efficient therapeutic tool for motor neuron diseases, including amyotrophic lateral sclerosis.}, } @article {pmid40006958, year = {2025}, author = {Mielcarska, MB and Rouse, BT}, title = {Viruses and the Brain-A Relationship Prone to Trouble.}, journal = {Viruses}, volume = {17}, number = {2}, pages = {}, pmid = {40006958}, issn = {1999-4915}, mesh = {Humans ; *Brain/virology ; *Viruses/pathogenicity ; Animals ; *Virus Diseases/virology/complications ; Neurodegenerative Diseases/virology ; Antiviral Agents/therapeutic use ; *Central Nervous System Viral Diseases/virology ; }, abstract = {Neurological disorders, some of which are associated with viral infections, are growing due to the aging and expanding population. Despite strong defenses of the central nervous system, some viruses have evolved ways to breach them, which often result in dire consequences. In this review, we recount the various ways by which different viruses can enter the CNS, and we describe the consequences of such invasions. Consequences may manifest as acute disease, such as encephalitis, meningitis, or result in long-term effects, such as neuromuscular dysfunction, as occurs in poliomyelitis. We discuss evidence for viral involvement in the causation of well-known chronic neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis, as well as vascular dementia in the elderly. We also describe the approaches currently available to control a few of the neural viral infections. These include antivirals that are effective against human immunodeficiency virus and herpes simplex virus, as well as vaccines valuable for controlling rabies virus, poliomyelitis virus, and some flavivirus infections. There is an urgent need to better understand, at a molecular level, how viruses contribute to acute and, especially, chronic neurological diseases and to develop more precise and effective vaccines and therapies.}, } @article {pmid40006784, year = {2025}, author = {Ji, M and Yu, H and Cui, H and Chen, J and Yu, J and Li, X}, title = {A New Pro-197-Ile Mutation in Amaranthus palmeri Associated with Acetolactate Synthase-Inhibiting Herbicide Resistance.}, journal = {Plants (Basel, Switzerland)}, volume = {14}, number = {4}, pages = {}, pmid = {40006784}, issn = {2223-7747}, support = {CARS25//China Agriculture Research System/ ; }, abstract = {Palmer amaranth (Amaranthus palmeri S. Watson), native to North America, is one of the most prominent invasive weed species on agricultural land. Acetolactate synthase (ALS)-resistant A. palmeri (Amaranthus palmeri) is widespread, while the research focus on resistance pattern and molecular basis of A. palmeri to imazethapyr is seldom documented in China. An A. palmeri population that survived the recommended rate of imazethapyr was collected in Shandong Province, China. The resistant mechanism and pattern of A. palmeri to imazethapyr was investigated. Dose-response assay showed that the resistant (R) population displayed a high resistance level (292.5-fold) to imazethapyr compared with the susceptible (S) population. Sequence analysis of the ALS gene revealed that nucleotide mutations resulted in three resistance-conferring amino acid substitutions, Pro-197-Ile, Trp-574-Leu, and Ser-653-Asp, in the individual plants of the R population. An in vitro enzyme assay indicated that the ALS was relatively unsusceptible to imazethapyr in the R population, showing a resistance index of 88.6-fold. ALS gene expression and copy number did not confer resistance to imazethapyr in the R population. Pro-197-Ile is the first reported amino acid substitution conferring ALS resistance to A. palmeri. This is the first case of an imazethapyr-resistant A. palmeri biotype in China.}, } @article {pmid40004464, year = {2025}, author = {Liu, Z and Song, SY}, title = {Genomic and Transcriptomic Approaches Advance the Diagnosis and Prognosis of Neurodegenerative Diseases.}, journal = {Genes}, volume = {16}, number = {2}, pages = {}, pmid = {40004464}, issn = {2073-4425}, mesh = {Humans ; *Neurodegenerative Diseases/genetics/diagnosis ; Prognosis ; *Transcriptome/genetics ; *Genomics/methods ; Genome-Wide Association Study ; Gene Expression Profiling/methods ; Parkinson Disease/genetics/diagnosis ; }, abstract = {Neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS), represent a growing societal challenge due to their irreversible progression and significant impact on patients, caregivers, and healthcare systems. Despite advances in clinical and imaging-based diagnostics, these diseases are often detected at advanced stages, limiting the effectiveness of therapeutic interventions. Recent breakthroughs in genomic and transcriptomic technologies, including whole-genome sequencing, single-cell RNA sequencing (scRNA-seq), and CRISPR-based screens, have revolutionized the field, offering new avenues for early diagnosis and personalized prognosis. Genomic approaches have elucidated disease-specific genetic risk factors and molecular pathways, while transcriptomic studies have identified stage-specific biomarkers that correlate with disease progression and severity. Furthermore, genome-wide association studies (GWAS), polygenic risk scores (PRS), and spatial transcriptomics are enabling the stratification of patients based on their risk profiles and prognostic trajectories. Advances in functional genomics have uncovered actionable targets, such as ATXN2 in ALS and TREM2 in AD, paving the way for tailored therapeutic strategies. Despite these achievements, challenges remain in translating genomic discoveries into clinical practice due to disease heterogeneity and the complexity of neurodegenerative pathophysiology. Future integration of genetic technologies holds promise for transforming diagnostic and prognostic paradigms, offering hope for improved patient outcomes and precision medicine approaches.}, } @article {pmid40004056, year = {2025}, author = {Yan, B and Suen, MC and Xu, N and Lu, C and Liu, C and Zhu, G}, title = {G-Quadruplex Structures Formed by Human Telomere and C9orf72 GGGGCC Repeats.}, journal = {International journal of molecular sciences}, volume = {26}, number = {4}, pages = {}, pmid = {40004056}, issn = {1422-0067}, support = {32071188//National Scientific Foundation of China/ ; 16101120, 161011121, AoE/M-403-16, AoE/M-401/20//Research Grants Council of the Hong Kong Special Administrative Region, China/ ; BGF.2023.019//Hong Kong University of Science and Technology, China/ ; 2021A1515220104//Guangdong Basic and Applied Basic Research Foundation, China/ ; 32301012//Young Scientists Fund of the National Natural Science Foundation of China/ ; }, mesh = {Humans ; *G-Quadruplexes ; *Telomere/genetics/chemistry ; *C9orf72 Protein/genetics/chemistry ; Amyotrophic Lateral Sclerosis/genetics ; *DNA Repeat Expansion ; Frontotemporal Dementia/genetics ; }, abstract = {G-quadruplexes (G4s) are unique nucleic acid structures composed of guanine-rich (G-rich) sequences that can form diverse topologies based on the arrangement of their four strands. G4s have attracted attention for their potential roles in various biological processes and human diseases. In this review, we focus on the G4 structures formed by human telomeric sequences, (GGGTTA)n, and the hexanucleotide repeat expansion, (GGGGCC)n, in the first intron region of the chromosome 9 open reading frame 72 (C9orf72) gene, highlighting their structural diversity and biological significance. Human telomeric G4s play crucial roles in telomere retention and gene regulation. In particular, we provide an in-depth summary of known telomeric G4s and focus on our recently discovered chair-type conformation, which exhibits distinct folding patterns. The chair-type G4s represent a novel folding pattern with unique characteristics, expanding our knowledge of telomeric G4 structural diversity and potential biological functions. Specifically, we emphasize the G4s formed by the (GGGGCC)n sequence of the C9orf72 gene, which represents the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The thorough structural analysis in this review advances our comprehension of the disease mechanism and provides valuable insights into developing targeted therapeutic strategies in ALS/FTD.}, } @article {pmid40002740, year = {2025}, author = {Meng, K and Jia, H and Hou, X and Zhu, Z and Lu, Y and Feng, Y and Feng, J and Xia, Y and Tan, R and Cui, F and Yuan, J}, title = {Mitochondrial Dysfunction in Neurodegenerative Diseases: Mechanisms and Corresponding Therapeutic Strategies.}, journal = {Biomedicines}, volume = {13}, number = {2}, pages = {}, pmid = {40002740}, issn = {2227-9059}, support = {600791001//the Research Start-up Fund of Jining Medical University/ ; JYHL2021MS13//Research Fund for Lin He's Academician Workstation of New Medicine and Clinical Translation in Jining Medical University/ ; 81700055//the National Natural Science Foundation of China/ ; Grant No. D2016021//Outstanding Talent Research Funding of Xuzhou Medical University/ ; BK20160229//Natural Science Foundation of Jiangsu Province/ ; tsqn201909147//Taishan Scholars Program of Shandong Province/ ; G2Y-kJS-SD-2023-097//Co-construction of Science and Technology Projects by the Science and Technology Department of the State Administration of Traditional Chinese Medicine/ ; }, abstract = {Neurodegenerative disease (ND) refers to the progressive loss and morphological abnormalities of neurons in the central nervous system (CNS) or peripheral nervous system (PNS). Examples of neurodegenerative diseases include Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). Recent studies have shown that mitochondria play a broad role in cell signaling, immune response, and metabolic regulation. For example, mitochondrial dysfunction is closely associated with the onset and progression of a variety of diseases, including ND, cardiovascular diseases, diabetes, and cancer. The dysfunction of energy metabolism, imbalance of mitochondrial dynamics, or abnormal mitophagy can lead to the imbalance of mitochondrial homeostasis, which can induce pathological reactions such as oxidative stress, apoptosis, and inflammation, damage the nervous system, and participate in the occurrence and development of degenerative nervous system diseases such as AD, PD, and ALS. In this paper, the latest research progress of this subject is detailed. The mechanisms of oxidative stress, mitochondrial homeostasis, and mitophagy-mediated ND are reviewed from the perspectives of β-amyloid (Aβ) accumulation, dopamine neuron damage, and superoxide dismutase 1 (SOD1) mutation. Based on the mechanism research, new ideas and methods for the treatment and prevention of ND are proposed.}, } @article {pmid40002527, year = {2025}, author = {Eisen, A and Kiernan, MC}, title = {The Neonatal Microbiome: Implications for Amyotrophic Lateral Sclerosis and Other Neurodegenerations.}, journal = {Brain sciences}, volume = {15}, number = {2}, pages = {}, pmid = {40002527}, issn = {2076-3425}, abstract = {Most brain development occurs in the "first 1000 days", a critical period from conception to a child's second birthday. Critical brain processes that occur during this time include synaptogenesis, myelination, neural pruning, and the formation of functioning neuronal circuits. Perturbations during the first 1000 days likely contribute to later-life neurodegenerative disease, including sporadic amyotrophic lateral sclerosis (ALS). Neurodevelopment is determined by many events, including the maturation and colonization of the infant microbiome and its metabolites, specifically neurotransmitters, immune modulators, vitamins, and short-chain fatty acids. Successful microbiome maturation and gut-brain axis function depend on maternal factors (stress and exposure to toxins during pregnancy), mode of delivery, quality of the postnatal environment, diet after weaning from breast milk, and nutritional deficiencies. While the neonatal microbiome is highly plastic, it remains prone to dysbiosis which, once established, may persist into adulthood, thereby inducing the development of chronic inflammation and abnormal excitatory/inhibitory balance, resulting in neural excitation. Both are recognized as key pathophysiological processes in the development of ALS.}, } @article {pmid40002476, year = {2025}, author = {Raymond, J and Howard, IM and Berry, J and Larson, T and Horton, DK and Mehta, P}, title = {Head Injury and Amyotrophic Lateral Sclerosis: Population-Based Study from the National ALS Registry.}, journal = {Brain sciences}, volume = {15}, number = {2}, pages = {}, pmid = {40002476}, issn = {2076-3425}, support = {n/a/CC/CDC HHS/United States ; }, abstract = {Background/Objectives: To examine if head injury (HI) is associated with age at ALS diagnosis in the United States. Methods: In this cross-sectional populationf-based analysis, we identified patients with ALS who were registered from 2015 to 2023 who completed the Registry's head trauma survey module. The association between HI and age at ALS diagnosis was assessed using multivariate analysis. Results: Of the 3424 respondents, 56.6% had experienced a HI. The adjusted odds ratio (aOR) for an ALS diagnosis before age 60 years for patients with a HI was 1.24 (95% CI, 1.07-1.45). One or two HIs had an aOR of 1.15 (95% CI, 0.97-1.36), and five or more HIs had an aOR of 1.58 (95% CI, 1.19-2.09). HI before age 18 years yielded an aOR of 2.03 (95% CI, 1.53-2.70) as well as HI between the ages of 18 and 30 years (aOR = 1.48, 95% CI: 1.06-2.06)). When narrowing the analysis to patients with HI before age 18 compared with patients with no HI, we found an association with HI that led to an emergency department or hospital visit (aOR = 1.50 (95% CI: 1.21-1.86)). Conclusions: In this cross-sectional analysis of ALS patients, HIs occurring in childhood and early adulthood and the number of HIs increased the odds of being diagnosed before age 60 years. These results suggest that HI continues to be a risk factor for ALS and could be associated with a younger age of diagnosis.}, } @article {pmid40002468, year = {2025}, author = {Dawoody Nejad, L and Pioro, EP}, title = {Modeling ALS with Patient-Derived iPSCs: Recent Advances and Future Potentials.}, journal = {Brain sciences}, volume = {15}, number = {2}, pages = {}, pmid = {40002468}, issn = {2076-3425}, abstract = {Amyotrophic lateral sclerosis (ALS) is a terminal complex neurodegenerative disease, with 10-15% of cases being familial and the majority being sporadic with no known cause. There are no animal models for the 85-90% of sporadic ALS cases. More creative, sophisticated models of ALS disease are required to unravel the mysteries of this complicated disease. While ALS patients urgently require new medications and treatments, suitable preclinical in vitro models for drug screening are lacking. Therefore, human-derived induced pluripotent stem cell (hiPSC) technology offers the opportunity to model diverse and unreachable cell types in a culture dish. In this review, we focus on recent hiPSC-derived ALS neuronal and non-neuronal models to examine the research progress of current ALS 2D monocultures, co-cultures, and more complex 3D-model organoids. Despite the challenges inherent to hiPSC-based models, their application to preclinical drug studies is enormous.}, } @article {pmid40002444, year = {2025}, author = {Okoh, C and Mayall, L and Makin, SM and Chen, C and Zarotti, N}, title = {Non-Pharmacological Interventions for Caregivers of People with Motor Neurone Disease: A Scoping Review of Psychosocial Outcomes.}, journal = {Brain sciences}, volume = {15}, number = {2}, pages = {}, pmid = {40002444}, issn = {2076-3425}, abstract = {Objective: Caregivers of individuals with motor neurone disease (MND) face a wide range of psychosocial difficulties. To address these, non-pharmacological interventions have been trialled, showing promising results. However, no clear characterisation of the breadth of psychosocial constructs examined by the interventions is currently available, resulting in the lack of a core outcome set (COS). The present review explored the types of psychosocial outcomes investigated in studies that adopted non-pharmacological interventions with caregivers of people with MND. Methods: A scoping review was conducted across four major databases (Academic Search Ultimate, CINAHL, PsycINFO, and MEDLINE) from inception to the 1 March 2024. Results: From an initial return of 4802 citations, 10 were considered eligible for inclusion. A total of 10 main psychosocial outcomes were identified: anxiety and depression, psychological distress, resilience, caregiver burden, caregiver preparedness, self-efficacy, quality of life, spiritual wellbeing, and mindfulness. Conclusions: Caregiver burden and symptoms of anxiety and depression represent pivotal outcomes, but caution is advised with regard to caregiver burden's potential multidimensional structure. Psychological distress and quality of life are also commonly investigated, but clearer consensus is needed on their conceptualisation. There is a paucity of studies characterising important psychosocial outcomes such as resilience, problem-solving, self-efficacy, and mindfulness, while no investigations are available for relevant outcomes such as coping, isolation, and loneliness. Further research is warranted to address these gaps to improve our insight into non-pharmacological support for MND caregivers and ultimately lead to the development of a core psychosocial outcome set in this population.}, } @article {pmid40001624, year = {2025}, author = {Ma, B and Ren, J and Qian, X}, title = {Study on the Polarization of Astrocytes in the Optic Nerve Head of Rats Under High Intraocular Pressure: In Vitro.}, journal = {Bioengineering (Basel, Switzerland)}, volume = {12}, number = {2}, pages = {}, pmid = {40001624}, issn = {2306-5354}, support = {12472309 12072210//National Natural Science Foundation of China/ ; }, abstract = {Astrocytes, the most common glial cells in the optic nerve head (ONH), provide support and nutrition to retinal ganglion cells. This study aims to investigate the polarization types of astrocytes in the ONH of rats under high intraocular pressure (IOP) and explore signaling pathways potentially associated with different types of polarized astrocytes. The rat models with chronic high IOP were established. High IOP lasted for 2, 4, 6, and 8 weeks. Astrocytes were extracted from the ONH of rats using the tissue block cultivation method. Western blot was used to detect the expression of proteins associated with astrocyte polarization. Proteomics was employed to identify differential proteins associated with astrocyte polarization. Astrocytes polarized into A2 astrocytes after 2, 4, 6, and 8 weeks of high IOP, while polarization into A1 astrocytes began only after 8 weeks of high IOP. The differential proteins associated with A1 astrocyte polarization are primarily enriched in pathways of neurodegeneration with respect to multiple diseases, while the differential proteins associated with A2 astrocyte polarization are primarily enriched in pathways of spliceosome in amyotrophic lateral sclerosis. Our findings could provide a better understanding of the role of ONH astrocytes in the pathogenesis of glaucoma and offer new perspectives for glaucoma treatment.}, } @article {pmid40001529, year = {2025}, author = {Onu, CJ and Adu, M and Chakkour, M and Kumar, V and Greenberg, ML}, title = {Inositol Phosphates and Synthesizing Enzymes: Implications in Neurodegenerative Disorders.}, journal = {Biomolecules}, volume = {15}, number = {2}, pages = {}, pmid = {40001529}, issn = {2218-273X}, support = {R01 GM125082/GM/NIGMS NIH HHS/United States ; R35 GM149271/GM/NIGMS NIH HHS/United States ; GM149271/GF/NIH HHS/United States ; GM125082/GF/NIH HHS/United States ; }, mesh = {Humans ; *Inositol Phosphates/metabolism ; *Neurodegenerative Diseases/metabolism/enzymology ; Animals ; Inositol/metabolism ; Signal Transduction ; }, abstract = {Inositol is a vital sugar molecule involved in numerous signaling pathways required for cellular homeostasis and cell survival. Myo-inositol and its phospho-derivatives, inositol phosphates (IPs), are the most prevalent forms of inositol found in living cells. They are involved in regulating ion channels, metabolic flux, stress response, and other key biological processes. While emerging research has highlighted the significant roles of inositol phosphates in immunity, cancer, and metabolic diseases, there is a lack of comprehensive reviews on their roles in psychiatric and neurological disorders. This review aims to fill that gap by analyzing the existing literature on the importance of inositol phosphates in severe psychiatric and neurological conditions such as Parkinson's disease, Alzheimer's disease, bipolar disorder, amyotrophic lateral sclerosis, schizophrenia, and Huntington's disease, underscoring the potential to pave the way for new treatment regimens for these debilitating disorders targeting inositol pathways.}, } @article {pmid40001370, year = {2025}, author = {Silva Ortíz, YL and de Sousa, TC and Kruklis, NE and Galeano García, P and Brango-Vanegas, J and Soller Ramada, MH and Franco, OL}, title = {The Role of Amphibian AMPs Against Oxidative Stress and Related Diseases.}, journal = {Antibiotics (Basel, Switzerland)}, volume = {14}, number = {2}, pages = {}, pmid = {40001370}, issn = {2079-6382}, abstract = {Amphibians use their skin as an effective defense mechanism against predators and microorganisms. Specialized glands produce antimicrobial peptides (AMPs) that possess antioxidant properties, effectively reducing reactive oxygen species (ROS) levels. These peptides are promising candidates for treating diseases associated with oxidative stress (OS) and redox imbalance, including neurodegenerative disorders such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS), as well as age-related conditions, like cardiovascular diseases and cancer. This review highlights the multifaceted roles of AMPs and antioxidant peptides (AOPs) in amphibians, emphasizing their protective capabilities against oxidative damage. They scavenge ROS, activate antioxidant enzyme systems, and inhibit cellular damage. AOPs often share structural characteristics with AMPs, suggesting a potential evolutionary connection and similar biosynthetic pathways. Peptides such as brevinin-1FL and Cath-KP demonstrate neuroprotective effects, indicating their therapeutic potential in managing oxidative stress-related diseases. The antioxidant properties of amphibian-derived peptides pave the way for novel therapeutic developments. However, a deeper understanding of the molecular mechanisms underlying these peptides and their interactions with oxidative stress is essential to addressing ROS-related diseases and advancing therapeutic strategies in clinical practice.}, } @article {pmid40000803, year = {2025}, author = {Giblin, A and Cammack, AJ and Blomberg, N and Anoar, S and Mikheenko, A and Carcolé, M and Atilano, ML and Hull, A and Shen, D and Wei, X and Coneys, R and Zhou, L and Mohammed, Y and Olivier-Jimenez, D and Wang, LY and Kinghorn, KJ and Niccoli, T and Coyne, AN and van der Kant, R and Lashley, T and Giera, M and Partridge, L and Isaacs, AM}, title = {Neuronal polyunsaturated fatty acids are protective in ALS/FTD.}, journal = {Nature neuroscience}, volume = {28}, number = {4}, pages = {737-747}, pmid = {40000803}, issn = {1546-1726}, support = {K99 NS123242/NS/NINDS NIH HHS/United States ; R01 NS132836/NS/NINDS NIH HHS/United States ; NS123242//U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; NS132836//U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; R00 NS123242/NS/NINDS NIH HHS/United States ; }, mesh = {*Amyotrophic Lateral Sclerosis/metabolism/genetics/pathology ; Animals ; *Fatty Acids, Unsaturated/metabolism ; Humans ; *Frontotemporal Dementia/metabolism/genetics/pathology ; *Neurons/metabolism ; C9orf72 Protein/genetics ; Induced Pluripotent Stem Cells/metabolism ; Drosophila ; Disease Models, Animal ; Fatty Acid Desaturases/metabolism/genetics ; Animals, Genetically Modified ; Male ; Brain/metabolism ; }, abstract = {Here we report a conserved transcriptomic signature of reduced fatty acid and lipid metabolism gene expression in a Drosophila model of C9orf72 repeat expansion, the most common genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia (ALS/FTD), and in human postmortem ALS spinal cord. We performed lipidomics on C9 ALS/FTD Drosophila, induced pluripotent stem (iPS) cell neurons and postmortem FTD brain tissue. This revealed a common and specific reduction in phospholipid species containing polyunsaturated fatty acids (PUFAs). Feeding C9 ALS/FTD flies PUFAs yielded a modest increase in survival. However, increasing PUFA levels specifically in neurons of C9 ALS/FTD flies, by overexpressing fatty acid desaturase enzymes, led to a substantial extension of lifespan. Neuronal overexpression of fatty acid desaturases also suppressed stressor-induced neuronal death in iPS cell neurons of patients with both C9 and TDP-43 ALS/FTD. These data implicate neuronal fatty acid saturation in the pathogenesis of ALS/FTD and suggest that interventions to increase neuronal PUFA levels may be beneficial.}, } @article {pmid40000618, year = {2025}, author = {Ru, Q and Li, Y and Zhang, X and Chen, L and Wu, Y and Min, J and Wang, F}, title = {Iron homeostasis and ferroptosis in muscle diseases and disorders: mechanisms and therapeutic prospects.}, journal = {Bone research}, volume = {13}, number = {1}, pages = {27}, pmid = {40000618}, issn = {2095-4700}, support = {82071970//National Natural Science Foundation of China (National Science Foundation of China)/ ; 82072506//National Natural Science Foundation of China (National Science Foundation of China)/ ; 31970689//National Natural Science Foundation of China (National Science Foundation of China)/ ; 32330047//National Natural Science Foundation of China (National Science Foundation of China)/ ; 2024AFB971//Natural Science Foundation of Hubei Province (Hubei Provincial Natural Science Foundation)/ ; }, mesh = {Humans ; *Ferroptosis/physiology ; *Iron/metabolism ; *Homeostasis ; *Muscular Diseases/metabolism/pathology/therapy ; Animals ; Muscle, Skeletal/metabolism ; }, abstract = {The muscular system plays a critical role in the human body by governing skeletal movement, cardiovascular function, and the activities of digestive organs. Additionally, muscle tissues serve an endocrine function by secreting myogenic cytokines, thereby regulating metabolism throughout the entire body. Maintaining muscle function requires iron homeostasis. Recent studies suggest that disruptions in iron metabolism and ferroptosis, a form of iron-dependent cell death, are essential contributors to the progression of a wide range of muscle diseases and disorders, including sarcopenia, cardiomyopathy, and amyotrophic lateral sclerosis. Thus, a comprehensive overview of the mechanisms regulating iron metabolism and ferroptosis in these conditions is crucial for identifying potential therapeutic targets and developing new strategies for disease treatment and/or prevention. This review aims to summarize recent advances in understanding the molecular mechanisms underlying ferroptosis in the context of muscle injury, as well as associated muscle diseases and disorders. Moreover, we discuss potential targets within the ferroptosis pathway and possible strategies for managing muscle disorders. Finally, we shed new light on current limitations and future prospects for therapeutic interventions targeting ferroptosis.}, } @article {pmid39999835, year = {2025}, author = {Saxena, S and Liebscher, S}, title = {Boosting the X factor: Increasing XBP1s-mediated ER stress signaling protects motor neurons in ALS/FTD.}, journal = {Molecular therapy : the journal of the American Society of Gene Therapy}, volume = {33}, number = {3}, pages = {844-846}, pmid = {39999835}, issn = {1525-0024}, } @article {pmid39999167, year = {2025}, author = {Wang, HV and Xiang, JF and Yuan, C and Veire, AM and Gendron, TF and Murray, ME and Tansey, MG and Hu, J and Gearing, M and Glass, JD and Jin, P and Corces, VG and McEachin, ZT}, title = {pTDP-43 levels correlate with cell type-specific molecular alterations in the prefrontal cortex of C9orf72 ALS/FTD patients.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {122}, number = {9}, pages = {e2419818122}, pmid = {39999167}, issn = {1091-6490}, support = {F32 ES031827/ES/NIEHS NIH HHS/United States ; RM1 HG008935/HG/NHGRI NIH HHS/United States ; U01 MH116441/MH/NIMH NIH HHS/United States ; R35 NS111602/NS/NINDS NIH HHS/United States ; R35 GM139408/GM/NIGMS NIH HHS/United States ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism/genetics/pathology ; *C9orf72 Protein/genetics/metabolism ; *Prefrontal Cortex/metabolism/pathology ; *Frontotemporal Dementia/metabolism/genetics/pathology ; Male ; *DNA-Binding Proteins/metabolism/genetics ; Female ; Middle Aged ; Microglia/metabolism/pathology ; Aged ; Phosphorylation ; Neurons/metabolism/pathology ; }, abstract = {Repeat expansions in the C9orf72 gene are the most common genetic cause of amyotrophic lateral sclerosis and familial frontotemporal dementia (ALS/FTD). To identify molecular defects that take place in the dorsolateral frontal cortex of patients with C9orf72 ALS/FTD, we compared healthy controls with C9orf72 ALS/FTD donor samples staged based on the levels of cortical phosphorylated TAR DNA binding protein (pTDP-43), a neuropathological hallmark of disease progression. We identified distinct molecular changes in different cell types that take place during FTD development. Loss of neurosurveillance microglia and activation of the complement cascade take place early, when pTDP-43 aggregates are absent or very low, and become more pronounced in late stages, suggesting an initial involvement of microglia in disease progression. Reduction of layer 2-3 cortical projection neurons with high expression of CUX2/LAMP5 also occurs early, and the reduction becomes more pronounced as pTDP-43 accumulates. Several unique features were observed only in samples with high levels of pTDP-43, including global alteration of chromatin accessibility in oligodendrocytes, microglia, and astrocytes; higher ratios of premature oligodendrocytes; increased levels of the noncoding RNA NEAT1 in astrocytes and neurons, and higher amount of phosphorylated ribosomal protein S6. Our findings reveal progressive functional changes in major cell types found in the prefrontal cortex of C9orf72 ALS/FTD patients that shed light on the mechanisms underlying the pathology of this disease.}, } @article {pmid39998997, year = {2025}, author = {García-Casanova, PH and Vázquez-Costa, JF}, title = {Advances in the early diagnosis of amyotrophic lateral sclerosis.}, journal = {Expert review of neurotherapeutics}, volume = {25}, number = {4}, pages = {415-425}, doi = {10.1080/14737175.2025.2471556}, pmid = {39998997}, issn = {1744-8360}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis ; *Early Diagnosis ; Biomarkers ; Disease Progression ; Delayed Diagnosis ; }, abstract = {INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a rapidly progressing neurodegenerative disease. Despite rapid disease progression, diagnostic delay of 10-16 months persists, influenced by disease-specific factors and healthcare systems. Reducing it is crucial for early intervention, multidisciplinary care planning, and patient participation in clinical trials.

AREAS COVERED: The authors review relevant studies identified through PubMed from 1990 to 2024. The article explores factors contributing to diagnostic delay, the importance of early diagnosis, and strategies for improvement, including the role of diagnostic criteria and biomarkers.

EXPERT OPINION: Diagnosis of ALS remains clinical, with clinical expertise as the main modifiable factor in the diagnostic delay. Some biomarkers may be useful to speed up diagnosis at an earlier stage of the disease and in patients with atypical presentations or co-morbidities. However, the use of biomarkers for ALS diagnosis in clinical practice is far from being established and poses considerable challenges, including the lack of disease-specific biomarkers and the potential for delayed results. Until disease-specific biomarkers become available, early referral to ALS specialists, together with physician education programs, will remain the main tools to reduce diagnostic delay in the next years.}, } @article {pmid39998694, year = {2025}, author = {Paramasivan, NK and Sarker, P and Zekeridou, A and Staff, NP and Klein, CJ and McKeon, A and Pittock, SJ and Dubey, D}, title = {Upper motor neuron-predominant motor neuron disease: a novel immunotherapy-responsive association of GAD65 autoimmunity.}, journal = {Journal of neurology}, volume = {272}, number = {3}, pages = {230}, pmid = {39998694}, issn = {1432-1459}, support = {MN OHE#15//Minnesota Office of Higher Education/ ; }, mesh = {Humans ; Male ; *Glutamate Decarboxylase/immunology ; Female ; Middle Aged ; Aged ; Retrospective Studies ; *Motor Neuron Disease/immunology/therapy/blood/physiopathology ; *Immunotherapy/methods ; *Autoantibodies/blood/cerebrospinal fluid ; *Autoimmunity ; Adult ; }, abstract = {BACKGROUND: Autoimmune disorders can present as motor neuronopathies and need to be excluded prior to the diagnosis of amyotrophic lateral sclerosis (ALS). We aimed to characterize the clinical phenotypes of patients with motor neuron disease (MND) in the context of high-titer serum/CSF GAD65 antibodies (radioimmunoassay).

METHODS: A retrospective review of all Mayo patients (between 1/1/2003 and 12/31/2023) with motor neuronopathy and co-existing high-titer GAD65 antibodies (≥ 20 nmol/L in serum [equivalent to > 10,000 IU, ELISA] or detection in CSF) was performed. Clinical phenotypes and outcomes were compared with ALS patients diagnosed in the last 5 years (1/1/2019-12/31/2023) who tested negative for GAD65 IgG.

RESULTS: We identified 12 patients with high-titer GAD65 IgG and motor neuronopathy, who often had lower back spasms, history of an exaggerated startle response with immunotherapy responsiveness as compared to ALS patients. On further analysis, a subgroup of these patients with neurogenic changes on EMG, had an upper motor neuron (UMN) predominant syndrome (58%), with history of exaggerated startle (57%), lower back spasms (43%), tandem gait impairment (86%) and UMN bladder symptoms (71%) that were significantly different from the ALS controls. The UMN predominant GAD65 MN responded favorably to immunotherapy with stable electromyography; significantly lesser worsening in mRS and mortality on long-term follow-up.

DISCUSSION: An upper motor neuron predominant motor neuronopathy is a distinct manifestation of GAD65 autoimmunity. Co-existing symptoms like exaggerated startle response, lower back spasms, impaired tandem gait, and UMN bladder signs might warrant consideration of an immunotherapy trial, which could yield favorable results.}, } @article {pmid39997929, year = {2025}, author = {Newell, ME and Aravindan, A and Babbrah, A and Halden, RU}, title = {Epigenetic Biomarkers Driven by Environmental Toxins Associated with Alzheimer's Disease, Parkinson's Disease, and Amyotrophic Lateral Sclerosis in the United States: A Systematic Review.}, journal = {Toxics}, volume = {13}, number = {2}, pages = {}, pmid = {39997929}, issn = {2305-6304}, support = {GF000000002135//Glen Swette Memorial Fund/ ; }, abstract = {Environmental toxins and epigenetic changes have been linked to neurodegenerative diseases, including Alzheimer's Disease (AD), Parkinson's Disease (PD), and amyotrophic lateral sclerosis (ALS). This paper aimed to (i) identify environmental toxins associated with AD, PD, and ALS, (ii) locate potential industrial sources of toxins in the United States (U.S.), and (iii) assess epigenetic changes driven by exposure to toxins reported by patients. Environmental factors and epigenetic biomarkers of neurodegeneration were compiled from 69 studies in the literature using Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA) and geographic information system approaches. Some 127 environmental toxins have been associated or putatively associated with AD, PD, or ALS, with four toxic metals (As, Cd, Mn, and Hg) common to all three of these neurodegenerative diseases. Environmental toxins associated with epigenetic changes (e.g., DNA methylation) in patients include air pollutants, metals, and organic chemicals (e.g., pesticides, mycotoxins, and cyanotoxins). Geographic analysis showed that study locations (e.g., U.S., Europe, and East Asia) were selected by researchers based on convenience of access rather than exposure risk and disease prevalence. We conclude that several toxins and epigenetic markers shared among neurodegenerative diseases could serve as attractive future targets guiding environmental quality improvements and aiding in early disease detection.}, } @article {pmid39996748, year = {2025}, author = {Yang, HM}, title = {Mitochondrial Dysfunction in Neurodegenerative Diseases.}, journal = {Cells}, volume = {14}, number = {4}, pages = {}, pmid = {39996748}, issn = {2073-4409}, support = {2020R1A2C1011311//National Research Foundation of Korea/ ; }, mesh = {Humans ; *Neurodegenerative Diseases/metabolism/pathology ; *Mitochondria/metabolism/pathology ; Animals ; Oxidative Stress ; Mitophagy ; Reactive Oxygen Species/metabolism ; }, abstract = {Mitochondrial dysfunction represents a pivotal characteristic of numerous neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. These conditions, distinguished by unique clinical and pathological features, exhibit shared pathways leading to neuronal damage, all of which are closely associated with mitochondrial dysfunction. The high metabolic requirements of neurons make even minor mitochondrial deficiencies highly impactful, driving oxidative stress, energy deficits, and aberrant protein processing. Growing evidence from genetic, biochemical, and cellular investigations associates impaired electron transport chain activity and disrupted quality-control mechanisms, such as mitophagy, with the initial phases of disease progression. Furthermore, the overproduction of reactive oxygen species and persistent neuroinflammation can establish feedforward cycles that exacerbate neuronal deterioration. Recent clinical research has increasingly focused on interventions aimed at enhancing mitochondrial resilience-through antioxidants, small molecules that modulate the balance of mitochondrial fusion and fission, or gene-based therapeutic strategies. Concurrently, initiatives to identify dependable mitochondrial biomarkers seek to detect pathological changes prior to the manifestation of overt symptoms. By integrating the current body of knowledge, this review emphasizes the critical role of preserving mitochondrial homeostasis as a viable therapeutic approach. It also addresses the complexities of translating these findings into clinical practice and underscores the potential of innovative strategies designed to delay or potentially halt neurodegenerative processes.}, } @article {pmid39996723, year = {2025}, author = {Deecke, L and Ohlei, O and Goldeck, D and Homann, J and Toepfer, S and Demuth, I and Bertram, L and Pawelec, G and Lill, CM}, title = {Peripheral Immune Profiles in Individuals at Genetic Risk of Amyotrophic Lateral Sclerosis and Alzheimer's Disease.}, journal = {Cells}, volume = {14}, number = {4}, pages = {}, pmid = {39996723}, issn = {2073-4409}, support = {U54 NS092091/NS/NINDS NIH HHS/United States ; LI 2654/4-1//German Research Foundation/ ; #16SV5536K, #16SV5537, #16SV5538, #16SV5837, #01UW0808,01GL1716A, and 01GL1716B//Bundesministerium für Bildung und Forschung/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/immunology ; *Alzheimer Disease/genetics/immunology ; Female ; Male ; *Genetic Predisposition to Disease ; Aged ; Middle Aged ; Genome-Wide Association Study ; Risk Factors ; Polymorphism, Single Nucleotide/genetics ; Aged, 80 and over ; }, abstract = {The immune system plays a crucial role in the pathogenesis of neurodegenerative diseases. Here, we explored whether blood immune cell profiles are already altered in healthy individuals with a genetic predisposition to amyotrophic lateral sclerosis (ALS) or Alzheimer's disease (AD). Using multicolor flow cytometry, we analyzed 92 immune cell phenotypes in the blood of 448 healthy participants from the Berlin Aging Study II. We calculated polygenic risk scores (PGSs) using genome-wide significant SNPs from recent large genome-wide association studies on ALS and AD. Linear regression analyses were then performed of the immune cell types on the PGSs in both the overall sample and a subgroup of older participants (>60 years). While we did not find any significant associations between immune cell subtypes and ALS and AD PGSs when controlling for the false discovery rate (FDR = 0.05), we observed several nominally significant results (p < 0.05) with consistent effect directions across strata. The strongest association was observed with CD57+ CD8+ early-memory T cells and ALS risk (p = 0.006). Other immune cell subtypes associated with ALS risk included PD-1+ CD8+ and CD57+ CD4+ early-memory T cells, non-classical monocytes, and myeloid dendritic cells. For AD, naïve CD57+ CD8+ T cells and mature NKG2A+ natural killer cells showed nominally significant associations. We did not observe major immune cell changes in individuals at high genetic risk of ALS or AD, suggesting they may arise later in disease progression. Additional studies are required to validate our nominally significant findings.}, } @article {pmid39996599, year = {2025}, author = {Chowdhury, RN and Azam, MA and Azam, SA and Lana, S and Culver, EN and Garruto, RM and Wander, K}, title = {Elevated Serum MCP-2 and TARC Associated With Increased Risk of Death in Guamanian ALS Patients.}, journal = {European journal of neurology}, volume = {32}, number = {3}, pages = {e70088}, pmid = {39996599}, issn = {1468-1331}, support = {//Sigma Xia/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/mortality/blood ; Male ; Female ; Middle Aged ; *Chemokine CCL2/blood ; Aged ; Adult ; *Chemokine CCL20/blood ; Guam/epidemiology ; }, abstract = {BACKGROUND: This study explores the relationship between inflammation and longevity in a high-incidence focus of amyotrophic lateral sclerosis (ALS) in post-WWII Guam. Characteristics of this focus include the sudden appearance of the disease in high numbers and the unusually long lifespan (without medical interventions) seen in some cases. We used bio-banked specimens to evaluate the relationship between serum immunoregulators and survival time.

METHODS: We evaluated sera from 69 Guam ALS cases collected within 2 years of symptom onset by NIH researchers from 1950 to 1983 for 11 immunoregulators via ELISA (CRP, eotaxin-1, RANTES, IL-6, IL-8, IL-10, IFN-γ, IP-10, MCP-1, MCP-2 and TARC). Factor analysis identified two factors responsible for ~68% of the variation in the data. We estimated Cox proportional hazards models to identify immunoregulators associated with time to death.

RESULTS: Each 10-unit increase in factor 2 cytokines (MCP-2 and TARC) was associated with a 38% increase in the risk of death (HR: 1.38; 95% CI: 1.19, 1.65; p: 0.00).

DISCUSSION: Like sporadic ALS cases worldwide, inflammation is associated with a shortened lifespan in Guamanian ALS; more specifically, our findings suggest serum levels of MCP-2 and TARC at onset may predict disease duration. Further investigation is needed to determine the role of these immunoregulators in disease prognosis and as targets for diagnostic and therapeutic interventions.}, } @article {pmid39996130, year = {2025}, author = {Dilliott, AA and Costanzo, MC and Bandres-Ciga, S and Blauwendraat, C and Casey, B and Hoang, Q and Iwaki, H and Jang, D and Kim, JJ and Leonard, HL and Levine, KS and Makarious, M and Nguyen, TT and Rouleau, GA and Singleton, AB and Smadbeck, P and Solle, J and Vitale, D and Nalls, M and Flannick, J and Burtt, NP and Farhan, SMK}, title = {The Neurodegenerative Disease Knowledge Portal: Propelling Discovery Through the Sharing of Neurodegenerative Disease Genomic Resources.}, journal = {Neurology. Genetics}, volume = {11}, number = {2}, pages = {e200246}, pmid = {39996130}, issn = {2376-7839}, abstract = {Although large-scale genetic association studies have proven useful for the delineation of neurodegenerative disease processes, we still lack a full understanding of the pathologic mechanisms of these diseases, resulting in few appropriate treatment options and diagnostic challenges. To mitigate these gaps, the Neurodegenerative Disease Knowledge Portal (NDKP) was created as an open-science initiative with the aim to aggregate, enable analysis, and display all available genomic datasets of neurodegenerative disease, while protecting the integrity and confidentiality of the underlying datasets. The portal contains 218 genomic datasets, including genotyping and sequencing studies, of individuals across 10 different phenotypic groups, including neurologic conditions such as Alzheimer disease, amyotrophic lateral sclerosis, Lewy body dementia, and Parkinson disease. In addition to securely hosting large genomic datasets, the NDKP provides accessible workflows and tools to effectively use the datasets and assist in the facilitation of customized genomic analyses. Here, we summarize the genomic datasets currently included within the portal, the bioinformatics processing of the datasets, and the variety of phenotypes captured. We also present example use cases of the various user interfaces and integrated analytic tools to demonstrate their extensive utility in enabling the extraction of high-quality results at the source, for both genomics experts and those in other disciplines. Overall, the NDKP promotes open science and collaboration, maximizing the potential for discovery from the large-scale datasets researchers and consortia are expending immense resources to produce and resulting in reproducible conclusions to improve diagnostic and therapeutic care for patients with neurodegenerative disease.}, } @article {pmid39995927, year = {2025}, author = {McDonald, TS and Cui, CS and Lerskiatiphanich, T and Marallag, J and Lee, JD}, title = {Metabolic rate and insulin-independent glucose uptake increase in a TDP-43[Q331K] mouse model of amyotrophic lateral sclerosis.}, journal = {Heliyon}, volume = {11}, number = {3}, pages = {e42482}, pmid = {39995927}, issn = {2405-8440}, abstract = {Impaired glucose regulation is increasingly recognised in amyotrophic lateral sclerosis (ALS), yet the precise mechanisms remain unclear. Here, we investigated energy balance and glucose control in TAR DNA-binding protein 43 (TDP-43)[Q331K] mice, a model of ALS, at both the early and late symptomatic stages of disease. Mutant TDP-43[Q331K] mice and non-transgenic controls underwent indirect calorimetry, as well as intraperitoneal glucose, insulin, and glucagon tolerance testing. We also examined plasma hormone levels and quantified α- and β-cell areas in pancreatic islets. Throughout disease progression, TDP-43[Q331K] mice exhibited elevated metabolic rates, with a transient increase in food intake at the early stages. At the later stages of disease, heightened glucose uptake was observed despite unchanged insulin secretion or tolerance, indicating mechanisms independent of insulin. Notably, TDP-43[Q331K] mice maintained fasting blood glucose levels even when circulating glucagon levels were reduced, suggesting that alternative pathways contribute to preserving euglycemia. These findings reveal a distinct metabolic profile in TDP-43[Q331K] mice, underscoring the complexity of glucose dyshomeostasis in ALS.}, } @article {pmid39995125, year = {2025}, author = {Kalinin, AP and Zubkova, ES and Menshikov, MY and Parfyonova, YV}, title = {ISR Modulators in Neurological Diseases.}, journal = {Current neuropharmacology}, volume = {23}, number = {10}, pages = {1184-1214}, pmid = {39995125}, issn = {1875-6190}, support = {23-15-00539//Russian Science Foundation, RSF/ ; }, mesh = {Humans ; *Nervous System Diseases/metabolism/drug therapy ; Animals ; *Signal Transduction/drug effects/physiology ; *Stress, Physiological/physiology/drug effects ; }, abstract = {The dysfunction of different cells lies in the pathogenesis of neurological diseases and is usually associated with cellular stress. Various stressors trigger the integrated stress response (ISR) signaling, whose highly conserved mechanism is primarily aimed at protecting a stress-exposed cell to cope as safely as possible with such stressful conditions. On the contrary, if a cell is unable to cope with excessive stress, the ISR can induce apoptosis. The ISR mechanism, whose main stage is the inhibition of translation machinery in favor of the synthesis of specific proteins, including the transcription factors ATF3, ATF4, CEBPA, and CEBPB, which function only as dimers and determine the uniqueness of the ISR response in each individual case, thus ensures different outcomes of the ISR. Inhibition of global protein synthesis is achieved through phosphorylation of eIF2α by PERK, HRI, PKR, or GCN2. To date, a number of compounds have been developed that modulate the ISR, including activators and inhibitors of the abovementioned ISR kinases as well as modulators of p-eIF2α dephosphorylation. They target different ISR stages, allowing a broad ISR modulation strategy. At the same time, there are no drugs that are both exceptionally safe and effective for the treatment of several neurological diseases, so there is an urgent need for new approaches to the treatment of these disorders. In this review, we represent ISR signaling as an important participant in the pathogenesis of neurological diseases. We also describe how various ISR modulators may become a part of future therapies for these diseases.}, } @article {pmid39995102, year = {2025}, author = {Perdikakis, M and Papadimitrakis, D and Floros, N and Tzavellas, E and Piperi, C and Gargalionis, AN and Papavassiliou, AG}, title = {Diagnostic role of circulating cell-free DNA in schizophrenia and neuro-degenerative disorders.}, journal = {Biomarkers in medicine}, volume = {19}, number = {5}, pages = {165-176}, pmid = {39995102}, issn = {1752-0371}, mesh = {Humans ; *Cell-Free Nucleic Acids/blood ; *Schizophrenia/diagnosis/blood/genetics ; *Neurodegenerative Diseases/diagnosis/blood/genetics ; Biomarkers/blood ; }, abstract = {Over the past few years, circulating cell-free DNA (cfDNA) research has grown exponentially. Several studies have associated the release of cfDNA in the bloodstream, cerebrospinal fluid, and other body fluids with increased apoptosis and cell death. Therefore, their possible use as biomarkers for cancer and other diseases has emerged. The diagnosis of pathological entities such as schizophrenia and neurodegenerative diseases involves many challenges and requires ruling out conditions with similar symptoms. In this context, cfDNA could serve as a valuable diagnostic biomarker. This study encompasses the recent bibliography and research regarding the utilization of circulating cfDNA for diagnostic purposes in schizophrenia, Alzheimer's disease, Parkinson's disease, multiple sclerosis, amyotrophic lateral sclerosis, and Huntington's disease. This minimally invasive method has provided important evidence regarding the diagnosis of the aforementioned diseases although further research is necessary.}, } @article {pmid39995075, year = {2025}, author = {Manco, C and Righi, D and Primiano, G and Romano, A and Luigetti, M and Leonardi, L and De Stefano, N and Plantone, D}, title = {Peripherin, A New Promising Biomarker in Neurological Disorders.}, journal = {The European journal of neuroscience}, volume = {61}, number = {4}, pages = {e70030}, pmid = {39995075}, issn = {1460-9568}, mesh = {Humans ; *Peripherins/metabolism/genetics/blood ; Biomarkers/metabolism/blood ; Animals ; *Nervous System Diseases/metabolism/diagnosis ; }, abstract = {Peripherin is a class III intermediate filament protein that has recently gained attention as a potential biomarker for axonal damage in the peripheral nervous system. This review examines peripherin gene expression, protein structure, and its functions in both healthy and diseased states. Peripherin is predominantly expressed in the peripheral nervous system, especially in motor and sensory neurons, and plays a critical role in neurite growth, stability, and axonal transport during myelination. Its expression is regulated by various cytokines and undergoes several post-transcriptional modifications. Peripherin interacts with multiple proteins, including neurofilaments and kinases, influencing cytoskeletal dynamics and neuronal functions. The review also explores peripherin involvement in several neurological disorders, such as Amyotrophic Lateral Sclerosis, where its abnormal expression and aggregation contribute to disease pathology. Additionally, peripherin has been linked to polyneuropathies, traumatic axonal injury, and diabetic neuropathy, suggesting its broader relevance as a biomarker in these conditions. The potential of peripherin as a biomarker is further supported by recent studies using ultrasensitive detection methods, which have identified elevated peripherin levels in the serum of patients with neurological diseases. Despite the promising findings, the application of peripherin as a biomarker in clinical settings remains limited, primarily due to challenges in its detection and the need for further validation in diverse patient populations. Future research directions include the development of more sensitive assays and the exploration of peripherin's role in non-neuronal tissues, which may expand its diagnostic and therapeutic potential.}, } @article {pmid39994742, year = {2025}, author = {Djukic, S and Zhao, Z and Jørgensen, LMH and Bak, AN and Jensen, DB and Meehan, CF}, title = {TDP-43 pathology is sufficient to drive axon initial segment plasticity and hyperexcitability of spinal motoneurones in vivo in the TDP43-ΔNLS model of Amyotrophic Lateral Sclerosis.}, journal = {Acta neuropathologica communications}, volume = {13}, number = {1}, pages = {42}, pmid = {39994742}, issn = {2051-5960}, support = {R370-2021-1109//The Lundbeck Foundation/ ; }, mesh = {Animals ; *Amyotrophic Lateral Sclerosis/pathology/genetics/physiopathology/metabolism ; *Motor Neurons/pathology/physiology ; Disease Models, Animal ; *DNA-Binding Proteins/genetics/metabolism ; *Spinal Cord/pathology/physiopathology ; Mice, Transgenic ; *Neuronal Plasticity/physiology ; Mice ; *Axon Initial Segment/pathology/physiology ; Action Potentials/physiology ; Male ; Humans ; *Axons/pathology ; }, abstract = {A hyperexcitability of the motor system is consistently observed in Amyotrophic Lateral Sclerosis (ALS) and has been implicated in the disease pathogenesis. What drives this hyperexcitability in the vast majority of patients is unknown. This is important to know as existing treatments simply reduce all neuronal excitability and fail to distinguish between pathological changes and important homeostatic changes. Understanding what drives the initial pathological changes could therefore provide better treatments. One challenge is that patients represent a heterogeneous population and the vast majority of cases are sporadic. One pathological feature that almost all (~97%) cases (familial and sporadic) have in common are cytoplasmic aggregates of the protein TDP-43 which is normally located in the nucleus. In our experiments we investigated whether this pathology was sufficient to increase neuronal excitability and the mechanisms by which this occurs. We used the TDP-43(ΔNLS) mouse model which successfully recapitulates this pathology in a controllable way. We used in vivo intracellular recordings in this model to demonstrate that TDP-43 pathology is sufficient to drive a severe hyper-excitability of spinal motoneurones. Reductions in soma size and a lengthening and constriction of axon initial segments were observed, which would contribute to enhanced excitability. Resuppression of the transgene resulted in a return to normal excitability parameters by 6-8 weeks. We therefore conclude that TDP-43 pathology itself is sufficient to drive a severe but reversible hyperexcitability of spinal motoneurones.}, } @article {pmid39994160, year = {2025}, author = {Dubey, PR and Kaur, G and Shukla, R}, title = {Nano-mediated Management of Metal Toxicity-induced Neurodegeneration: A Critical Review.}, journal = {Molecular neurobiology}, volume = {62}, number = {7}, pages = {8400-8419}, pmid = {39994160}, issn = {1559-1182}, mesh = {Humans ; Animals ; *Neurodegenerative Diseases/chemically induced/therapy ; *Metals, Heavy/toxicity ; *Nanotechnology/methods ; *Nanoparticles/therapeutic use ; Oxidative Stress/drug effects ; Drug Delivery Systems/methods ; }, abstract = {Heavy metals, omnipresent in the environment, though imperative in trace quantities for human physiology, become a serious health hazard due to their toxicity. Copper, arsenic, lead, iron, and mercury are some examples of the heavy metals responsible for oxidative stress, which is one of the primary factors behind neurodegenerative diseases like Alzheimer's, Parkinson's, and amyotrophic lateral sclerosis. Neurodegeneration is caused by toxicity due to environmental exposure to these toxic substances or genetic variation. Conventional therapies, relying on chelation and antioxidants, suffer from the broader perspective of metal removal in a non-selective manner and poor targeting of the brain. In this respect, treatments based on nanotechnology that employ nanoparticles such as dendrimers, micelles, and liposomes constitute a promising interest in enhancing drug delivery with minimal neurotoxicity. The present review outlines the heavy metals responsible for neurodegenerative diseases, their pathophysiology, management strategies available at present, and the scope of nanotechnology intervention in overcoming shortcomings of conventional therapies. The genetic influence of heavy metals on neurological health is also part of this article.}, } @article {pmid39993605, year = {2025}, author = {David Wu, CH and Whelan, TJ and Swaminath, A}, title = {Response to: Comment on Wu et al's article on toxicity in patients receiving radiotherapy for ultracentral stage I non-small cell lung cancer.}, journal = {Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology}, volume = {206}, number = {}, pages = {110804}, doi = {10.1016/j.radonc.2025.110804}, pmid = {39993605}, issn = {1879-0887}, } @article {pmid39993604, year = {2025}, author = {Huertas, A and Moghanaki, D and Siva, S}, title = {Comment on Wu et al's article on toxicity in patients receiving radiotherapy for ultracentral stage I non-small cell lung cancer.}, journal = {Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology}, volume = {206}, number = {}, pages = {110805}, doi = {10.1016/j.radonc.2025.110805}, pmid = {39993604}, issn = {1879-0887}, } @article {pmid39992908, year = {2025}, author = {Nemeth, T and Zarnocki, A and Ladanyi, A and Papp, C and Ayaydin, F and Szebeni, GJ and Gacser, A}, title = {PCR-based CRISPR/Cas9 system for fluorescent tagging: A tool for studying Candida parapsilosis virulence.}, journal = {PloS one}, volume = {20}, number = {2}, pages = {e0312948}, pmid = {39992908}, issn = {1932-6203}, mesh = {*CRISPR-Cas Systems/genetics ; *Candida parapsilosis/pathogenicity/genetics/isolation & purification ; Animals ; Mice ; Virulence/genetics ; *Polymerase Chain Reaction/methods ; Macrophages/microbiology ; Humans ; Candidiasis/microbiology ; Cell Line ; }, abstract = {Candida parapsilosis is persistent in a hospital environment hence it is often associated with nosocomial infections especially amongst low-birth weight neonates. Genetic modification is therefore important to characterise the physiological and virulence related properties of this fungus. A PCR-based CRISPR/Cas9 system has been adopted to facilitate the generation of fluorescent tagged prototroph isolates. We examined a total of eight fluorescent protein coding genes, out of which three were found to be applicable for simultaneous utilisation. We investigated three clinical isolates of C. parapsilosis in terms of their adherence to silicone and their uptake by J774.2 murine macrophages in competition assays. Interestingly, we found significant differences between them in both experiments where GA1 isolate was significantly less resistant to macrophage uptake and CDC317 was significantly more adherent to silicone material. In silico analysis of the agglutinin-like sequences (Als) exposed remarkable diversity in this protein family and additionally, the thorough analysis of the ALS genes revealed evidence of formation of a new gene by intrachromosomal recombination in the GA1 isolate. Finally, we provide a step by step protocol for the application of the PCR-based CRISPR/Cas9 system for fluorescently labelling C. parapsilosis isolates.}, } @article {pmid39992655, year = {2025}, author = {Liu, X and Shang, H and Wei, Q and Yao, X and Lian, L and Dang, J and Jia, R and Wu, Z and Li, H and Niu, Q and Cheng, X and Zou, Z and Chen, S and Zhang, M and Liu, Y and Liu, Y and Liu, Q and Huang, X and Wang, H and Feng, H and Wang, S and Fan, D and , }, title = {Tetramethylpyrazine Nitrone in Amyotrophic Lateral Sclerosis: A Randomized Clinical Trial.}, journal = {JAMA network open}, volume = {8}, number = {2}, pages = {e2461055}, pmid = {39992655}, issn = {2574-3805}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy ; *Pyrazines/therapeutic use/administration & dosage ; Male ; Female ; Middle Aged ; Aged ; Double-Blind Method ; China ; Treatment Outcome ; }, abstract = {IMPORTANCE: Tetramethylpyrazine nitrone has exhibited promising results in improving motor dysfunction in neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS).

OBJECTIVE: To evaluate the safety and efficacy of orally administered tetramethylpyrazine nitrone in patients with ALS.

This phase 2, multicenter, double-masked, placebo-controlled, randomized clinical trial was conducted from December 24, 2020, through July 14, 2023, in 11 centers in China, with a 180-day follow-up. Patients aged 45 to 70 years, with ALS onset within 2 years, ALS Functional Rating Scale-Revised (ALSFRS-R) scores of at least 2 points on each item, and forced vital capacity (FVC) of at least 80% were included. Patients experienced a 1- to 4-point decrease in ALSFRS-R score during a 3-month screening period.

INTERVENTIONS: Patients were randomly assigned 1:1:1 to receive low-dose tetramethylpyrazine nitrone (600 mg twice daily), high-dose tetramethylpyrazine nitrone (1200 mg twice daily), or placebo (twice daily) for 180 days.

MAIN OUTCOMES AND MEASURES: The primary outcome was change in ALSFRS-R score (range of 0-48, with lower scores indicating worse function) from baseline to 180 days. The secondary outcomes were changes in FVC, grip strength, ALS Assessment Questionnaire-40 (ALSAQ-40) score, and end point events. Safety outcomes included adverse events.

RESULTS: A total of 155 patients (mean [SD] age, 55.0 [6.5] years; 115 men [74.2%]) were randomized (51 [32.9%] to the low-dose tetramethylpyrazine nitrone group, 52 [33.6%] to the high-dose tetramethylpyrazine nitrone group, and 52 [33.6%] to the placebo group). No significant differences were observed in ALSFRS-R score changes between low-dose tetramethylpyrazine nitrone (least squares [LS] mean difference, -0.89 points; 95% CI -3.25 to 1.48 points) and high-dose tetramethylpyrazine nitrone (LS mean difference, -0.20 points; 95% CI -2.48 to 2.07 points) compared with placebo. High-dose tetramethylpyrazine nitrone showed a significantly slower decline in grip strength at day 180 (LS mean difference, 2.46 kg; 95% CI, 0.15-4.76 kg). In a subgroup of patients younger than 65 years with slower disease progression, tetramethylpyrazine nitrone significantly attenuated the decline in grip strength (LS mean difference, 3.63 kg; 95% CI, 0.84-6.41 kg), bulbar scores (LS mean difference, 0.66 points; 95% CI, 0.03-1.29 points), and respiratory scores (LS mean difference, 0.54 points; 95% CI, 0.03-1.06 points). Adverse events were mostly mild or moderate, with no severe treatment-related adverse events or deaths.

CONCLUSIONS AND RELEVANCE: This randomized clinical trial demonstrates that tetramethylpyrazine nitrone is safe and well-tolerated in patients with ALS. There was no difference in the primary end point across the low-dose, high-dose, and placebo groups, with significant benefits in a subgroup of younger patients with slower disease progression.

TRIAL REGISTRATION: ChiCTR Identifier: ChiCTR2000039689.}, } @article {pmid39991082, year = {2025}, author = {Chen, G and Cao, Y and Du, X and Cui, J and Zeng, X and Yang, H and Ren, Z and Xu, K}, title = {The Clinical Research Landscape of Intracranial Nicardipine for Aneurysmal Subarachnoid Hemorrhage: Insights From Bibliometric Analysis.}, journal = {Drug design, development and therapy}, volume = {19}, number = {}, pages = {1129-1146}, pmid = {39991082}, issn = {1177-8881}, mesh = {*Nicardipine/administration & dosage/therapeutic use ; *Subarachnoid Hemorrhage/drug therapy ; Humans ; *Bibliometrics ; }, abstract = {BACKGROUND: The 2023 American Heart Association/American Stroke Association guideline and Wessels et al's 2024 randomized controlled trial highlight the potential benefits of intracranial nicardipine for aneurysmal subarachnoid hemorrhage (aSAH). This study aims to systematically identify the publication trends and research hotspots in this field through bibliometric analysis.

METHODS: Relevant publications were sourced from the Web of Science Core Collection (WoSCC). Bibliometric and visualization analyses were conducted using the online tools of the WoSCC database and CiteSpace 6.2.R6.

RESULTS: Analysis of 28 articles published by 158 researchers from 55 institutions across 8 countries revealed an intermittent small-scale growth in annual publication volume from 1994 to 2024, with a continuous rise in annual citation volume since 2005, indicating growing interest in the field. Japan, Germany, and the United States of America (USA) were the most prolific and influential countries. Institutions such as Tokyo Women's Medical University showed particularly significant contributions. Kasuya Hidetoshi was the most prolific author. There was little global collaboration among countries, institutions, and authors, with distinct regional research characteristics: Japan and Germany focused on intracranial implants, while the USA concentrated on intrathecal injections. Major publishing and co-cited journals included Neurocritical Care, Acta Neurochirurgica, Journal of Neurosurgery, and Stroke. Popular keywords in 2024 included "preventing cerebral vasospasm", "delayed cerebral ischemia", "outcome events", and "clinical trials", revealing current research hotspots.

CONCLUSION: This study maps the global clinical research landscape of intracranial application of nicardipine for aSAH from 1994 to 2024, providing valuable references and guidance for future research.}, } @article {pmid39990425, year = {2025}, author = {Chakraborty, A and Mitra, J and Malojirao, VH and Kodavati, M and Mandal, SM and Gill, SK and Sreenivasmurthy, SG and Vasquez, V and Mankevich, M and Bosch, LVD and Garruto, RM and Robey, IF and Krishnan, B and Ghosh, G and Hegde, M and Hazra, T}, title = {Fructose-2,6-bisphosphate restores TDP-43 pathology-driven genome repair deficiency in motor neuron diseases.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2024.11.13.623464}, pmid = {39990425}, issn = {2692-8205}, abstract = {TAR DNA-binding protein 43 (TDP-43) proteinopathy plays a critical role in neurodegenerative diseases, including amyotrophic lateral sclerosis and frontotemporal dementia (FTD). In our recent discovery, we identified that TDP-43 plays an essential role in DNA double-strand break (DSB) repair via the non-homologous end joining (NHEJ) pathway. Here, we found persistent DNA damage in the brains of ALS/FTD patients, primarily in the transcribed regions of the genome. We further investigated the underlying mechanism and found that polynucleotide kinase 3'-phosphatase (PNKP) activity was severely impaired in the nuclear extracts of both patient brains and TDP-43-depleted cells. PNKP is a key player in DSB repair within the transcribed genome, where its 3'-P termini processing activity is crucial for preventing persistent DNA damage and neuronal death. The inactivation of PNKP in ALS/FTD was due to reduced levels of its interacting partner, phosphofructo-2-kinase fructose 2,6 bisphosphatase (PFKFB3), and its biosynthetic product, fructose-2,6-bisphosphate (F2,6BP), an allosteric modulator of glycolysis. Recent work from our group has shown that F2,6BP acts as a positive modulator of PNKP activity in vivo. Notably, exogenous supplementation with F2,6BP restored PNKP activity in nuclear extracts from ALS/FTD brain samples and patient-derived induced pluripotent stem (iPS) cells harboring pathological mutations. Furthermore, we demonstrate that supplementation of F2,6BP restores genome integrity and partially rescues motor phenotype in a Drosophila model of ALS. Our findings underscore the possibility of exploring the therapeutic potential of F2,6BP or its analogs in TDP-43 pathology-associated motor neuron diseases.}, } @article {pmid39990107, year = {2025}, author = {Zhao, S and Chen, R and An, Y and Zhang, Y and Ma, C and Gao, Y and Lu, Y and Yang, F and Bai, X and Zhang, J}, title = {Optineurin overexpression ameliorates neurodegeneration through regulating neuroinflammation and mitochondrial quality in a murine model of amyotrophic lateral sclerosis.}, journal = {Frontiers in aging neuroscience}, volume = {17}, number = {}, pages = {1522073}, pmid = {39990107}, issn = {1663-4365}, abstract = {INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the loss of motor neurons (MNs). Genetic mutations in Optineurin (OPTN) and Superoxide Dismutase 1 (SOD1) have been identified as causal factors for ALS. OPTN immunopositive inclusions have been confirmed in the cases of ALS with SOD1 mutations. However, the role of the OPTN gene in ALS caused by SOD1 mutations is ambiguous.

METHODS: The murine Optn lentivirus and empty vector lentivirus were injected into SOD1 [G93A] mice after discovering variations in Optn expression over time. The phenotype onset date, life span, locomotor activity, and pathological changes in the spinal cord were determined and recorded subsequently. In addition, the influences on cellular apoptosis, mitochondrial dynamics, mitophagy, and neuroinflammation were further investigated.

RESULTS: Optn expression was increased in the spinal cord of SOD1 [G93A] mice at the pre-symptomatic phase, but decreased after disease onset. Optn overexpression led to a 9.7% delay in the onset of disease and improved motor performance in SOD1 [G93A] mice. Optn overexpression also ameliorated the MNs loss by 46.8%. Moreover, all these ameliorating effects induced by Optn overexpression might be due to the inhibition of cellular apoptosis, improvement of mitochondrial quality, regulation of mitochondrial dynamics, promotion of mitophagy, and anti-inflammatory properties.

CONCLUSION: Our data demonstrate that Optn overexpression protects MNs, inhibites cellular apoptosis, improves mitochondrial quality and regulates neuroinflamation in SOD1 [G93A] mice at the pre-symptomatic stage.}, } @article {pmid39989851, year = {2025}, author = {Rea, D and Tham, C and Tham, TC}, title = {Endoscopic calabash technique for gastric mesenchymal tumours: A low hanging fruit or a novel endoscopic technique?.}, journal = {World journal of gastrointestinal endoscopy}, volume = {17}, number = {2}, pages = {101676}, pmid = {39989851}, issn = {1948-5190}, abstract = {The term subepithelial lesions encompasses a wide array of pathology of which numerous benign and malignant pathologies are grouped. A subset of these lesions are termed gastric mesenchymal tumours of which some have innate malignant potential. Currently there is various guidance on the recommended approach to the investigation and management of these lesions and there exists multiple methods of resection. Lin et al have developed and proposed a new method of resection of these gastric mesenchymal tumours within the field of endoscopy, a procedure they have termed endoscopic calabash ligation and resection. This editorial aims to outlay the current landscape for gastric mesenchymal tumours with regards to the various guidelines and resection techniques while comparing Lin et al's new technique to those that are already established in the field of endoscopy. Advancements in endoscopy that maintain or improve patient outcomes compared to the gold standard approach are exciting developments. Lin et al's study suggests that their technique is comparable in regard to patient outcomes while simultaneously being more efficient in its use of hospital resources including procedural time. Whilst the data and analysis proposed in the study is promising, there are areas that need to be addressed before advocating the procedure for widespread use. However, with further studies and analysis this may be foreseeable in the future.}, } @article {pmid39989811, year = {2025}, author = {Marzi, I and Pieraccini, G and Bemporad, F and Chiti, F}, title = {Detection of an Intermediate in the Unfolding Process of the N-Terminal Domain of TDP-43.}, journal = {ACS omega}, volume = {10}, number = {6}, pages = {5616-5633}, pmid = {39989811}, issn = {2470-1343}, abstract = {TAR DNA-binding protein 43 (TDP-43) is a nuclear protein accumulating in intraneuronal cytoplasmic inclusions associated with amyotrophic lateral sclerosis, frontotemporal lobar degeneration with tau-negative/ubiquitin-positive inclusions, and limbic-predominant age-related TDP-43 encephalopathy. Oligomerization of full-length TDP-43, driven by its N-terminal domain (NTD), is essential for its function, but aberrant self-assembly also promotes liquid-liquid phase separation and formation of solid inclusions. Building on recent all-atom molecular dynamics simulations and using various biophysical approaches, we identified a partially unfolded state accumulating during unfolding of TDP-43 NTD, before the major energy barrier of unfolding is crossed. Intrinsic fluorescence spectroscopy coupled to a stopped-flow device at high urea concentration reveals that the intermediate state has a fluorescence emission distinct from those of the native and unfolded states and forms within the 14 ms dead time. Conventional fluorescence spectroscopy shows it still accumulates at moderate urea concentration. Circular dichroism and H/D exchange results show a species with an intermediate content of secondary structure and a distorted β-sheet, whereas SYPRO orange fluorescence indicates an open conformation with more exposed hydrophobic regions compared to the native state. Importantly, this intermediate is observed even at low protein concentration, when TDP-43 NTD is largely monomeric, indicating that its formation is independent of the initial TDP-43 NTD oligomeric state. Dynamic light scattering at high protein concentration shows that the intermediate is a partially folded dimer. The intermediate forms upon chemical denaturation and does not occur under thermal unfolding. Overall, the findings highlight the presence of one more partially folded state for TDP-43 NTD, underlining its high structural plasticity and suggesting that its distinct unfolding pathway may play a critical role in both its functional and pathological behaviors.}, } @article {pmid39989203, year = {2025}, author = {Wu, J and Sun, C and Xu, Y and Fan, D and Ye, S}, title = {The contralateral co-movement test in a Chinese population with amyotrophic lateral sclerosis.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {26}, number = {5-6}, pages = {426-435}, doi = {10.1080/21678421.2025.2467959}, pmid = {39989203}, issn = {2167-9223}, mesh = {Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; *Amyotrophic Lateral Sclerosis/physiopathology/diagnosis ; China ; *Functional Laterality/physiology ; Movement/physiology ; Prospective Studies ; East Asian People ; }, abstract = {INTRODUCTION: Mirror movements (MMs) are often overlooked in patients with amyotrophic lateral sclerosis (ALS). Although the contralateral co-movement (COMO) test can be used to evaluate MMs in patients with ALS, it lacks a systematic evaluation. The aim of this study was to validate the effectiveness of the Chinese version of the COMO test in a Chinese ALS population.

METHODS: We prospectively enrolled 173 patients with ALS as the disease group and 28 healthy individuals as controls. All participants were evaluated using the Chinese version of the COMO test. Univariate analysis and multiple linear regression were used to compare differences between groups. Subgroup analysis of the COMO scores was performed based on different disease characteristics.

RESULTS: The COMO score in the ALS group was significantly greater (5.00% [1.67-10.00]) than that in the healthy control group (1.67% [0.00-3.33]). After adjusting for confounders, this difference remained significant. Multivariate linear analysis suggested that the upper motor neuron (UMN) score independently predicted the COMO score (P < 0.001). The COMO score was not affected by different onset regions or lateralizations. Propensity score matching revealed no significant difference in COMO scores between uninvolved limb segments and the corresponding limb segments in other patients. The Cronbach's α of the Chinese COMO test was 0.621.

CONCLUSION: The Chinese COMO test can serve as a potential tool for assessing MMs in Chinese patients with ALS. The UMN score is a factor influencing the COMO score. The COMO test can provide objective evidence for ALS characteristics and the severity of UMN damage.}, } @article {pmid39987720, year = {2025}, author = {Ohnari, K and Mafune, K and Adachi, H}, title = {Usefulness of the Gold Coast criteria in diagnosing fast-progressing amyotrophic lateral sclerosis.}, journal = {Journal of the neurological sciences}, volume = {471}, number = {}, pages = {123418}, doi = {10.1016/j.jns.2025.123418}, pmid = {39987720}, issn = {1878-5883}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/physiopathology ; Male ; Female ; Middle Aged ; Disease Progression ; Retrospective Studies ; Aged ; Electromyography ; Sensitivity and Specificity ; Adult ; }, abstract = {The Gold Coast criteria are reportedly more sensitive for diagnosing amyotrophic lateral sclerosis (ALS) than the previously used criteria; however, the sensitivity of these sets of criteria among groups classified according to their prognosis has not been compared. In this study, we examined the difference in the sensitivity for ALS diagnosis among these criteria, especially in patients with fast-progression ALS. We enrolled 95 patients diagnosed with ALS and retrospectively classified them into three groups based on the interval between disease onset and death or tracheostomy. We retrospectively examined the number of patients meeting the Gold Coast, Awaji, or revised El Escorial criteria (rEEC) (definite/probable/possible) at initial clinical examination and electromyography and compared the rates of diagnosis according to each set of criteria among the three groups. The sensitivity of the Gold Coast criteria was significantly higher than that of the Awaji and rEEC criteria (sensitivity, 92.6 % vs. 71.8 % vs. 71.7 %, p < 0.001). The sensitivity of the Gold Coast criteria in patients with fast progression (n = 30) was significantly higher than that of the Awaji and rEEC criteria (sensitivity, 100 % vs. 73.3 % vs. 73.3 %, p = 0.001). Most patients diagnosed only based on the Gold Coast criteria had lower motor signs. Hence, the Gold Coast criteria are particularly useful for diagnosing fast-progression ALS.}, } @article {pmid39987392, year = {2025}, author = {Liu, Y and Xiang, J and Gong, H and Yu, T and Gao, M and Huang, Y}, title = {The Regulation of TDP-43 Structure and Phase Transitions: A Review.}, journal = {The protein journal}, volume = {44}, number = {2}, pages = {113-132}, pmid = {39987392}, issn = {1875-8355}, support = {22477022//National Natural Science Foundation of China/ ; }, mesh = {Humans ; *DNA-Binding Proteins/chemistry/metabolism/genetics ; Phase Transition ; *Amyotrophic Lateral Sclerosis/metabolism/genetics/pathology ; *Frontotemporal Dementia/metabolism/genetics/pathology ; Animals ; Protein Processing, Post-Translational ; }, abstract = {The transactive response DNA binding protein 43 (TDP-43) is an RNA/DNA-binding protein that is involved in a number of cellular functions, including RNA processing and alternative splicing, RNA transport and translation, and stress granule assembly. It has attracted significant attention for being the primary component of cytoplasmic inclusions in patients with amyotrophic lateral sclerosis or frontotemporal dementia. Mounting evidence suggests that both cytoplasmic aggregation of TDP-43 and loss of nuclear TDP-43 function contribute to TDP-43 pathology. Furthermore, recent studies have demonstrated that TDP-43 is an important component of many constitutive or stress-induced biomolecular condensates. Dysregulation or liquid-to-gel transition of TDP-43 condensates can lead to alterations in TDP-43 function and the formation of TDP-43 amyloid fibrils. In this review, we summarize recent research progress on the structural characterization of TDP-43 and the TDP-43 phase transition. In particular, the roles that disease-associated genetic mutations, post-translational modifications, and extrinsic stressors play in the transitions among TDP-43 monomers, liquid condensates, solid condensates, and fibrils are discussed. Finally, we discuss the effectiveness of available regulators of TDP-43 phase separation and aggregation. Understanding the underlying mechanisms that drive the pathological transformation of TDP-43 could help develop therapeutic strategies for TDP-43 pathology.}, } @article {pmid39987285, year = {2025}, author = {Fang, M and Zhou, Y and He, K and Lu, Y and Tao, F and Huang, H}, title = {Glucose Metabolic Reprogramming in Microglia: Implications for Neurodegenerative Diseases and Targeted Therapy.}, journal = {Molecular neurobiology}, volume = {62}, number = {7}, pages = {8204-8221}, pmid = {39987285}, issn = {1559-1182}, support = {82204651//National Natural Science Foundation of China/ ; }, mesh = {Humans ; *Microglia/metabolism/drug effects ; *Neurodegenerative Diseases/metabolism/drug therapy/pathology/therapy ; *Glucose/metabolism ; Animals ; *Molecular Targeted Therapy ; Glycolysis ; Metabolic Reprogramming ; }, abstract = {As intrinsic immune cells in the central nervous system, microglia play a crucial role in maintaining brain homeostasis. Microglia can transition from homeostasis to various responsive states in reaction to different external stimuli, undergoing corresponding alterations in glucose metabolism. In neurodegenerative diseases including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS), microglial glucose metabolic reprogramming is widespread. This reprogramming leads to changes in microglial function, exacerbating neuroinflammation and the accumulation of pathological products, thereby driving the progression of neurodegeneration. This review summarizes the specific alterations in glucose metabolism within microglia in AD, PD, ALS, and MS, as well as the corresponding treatments aimed at reprogramming glucose metabolism. Compounds that inhibit key glycolytic enzymes like hexokinase 2 (HK2) and pyruvate kinase M2 (PKM2), or activate regulators of energy metabolism such as AMP-activated protein kinase (AMPK), have shown significant potential in the treatment of various neurodegenerative diseases. However, current research faces numerous challenges, including side effects and blood-brain barrier (BBB) penetration of compounds. Screening relevant drugs from natural products, especially flavonoids, is a reliable approach. On the one hand, longtime herbal medical practices provide a certain degree of assurance regarding clinical safety, and their chemical properties contribute to effective BBB permeability. On the other hand, the concurrent anti-tumor and anti-neuroinflammatory activities of flavonoids suggest that regulation of glucose metabolism reprogramming might be a potential common mechanism of action. Notably, considering the dynamic nature of microglial metabolism, there is an urgent need to develop technologies for real-time monitoring of glucose metabolism processes, which would significantly advance research in this field.}, } @article {pmid39987111, year = {2025}, author = {Zeng, L and Yang, F and Xu, D and Zhou, J and Qiao, G and Wu, M and Li, C and Yu, Y and Qiu, Y and Liu, J}, title = {Actual needs of patients with amyotrophic lateral sclerosis: a qualitative study from Wuhan, China.}, journal = {BMC palliative care}, volume = {24}, number = {1}, pages = {50}, pmid = {39987111}, issn = {1472-684X}, support = {2023AFD160//Hubei Provincial Natural Science Foundation and Traditional Chinese Medicine Innovation and Development Joint/ ; 2024AFD279//Department of Science and Technology, Hubei Province, China/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/psychology/therapy/complications ; China ; Qualitative Research ; Male ; Female ; Middle Aged ; Aged ; Adult ; Quality of Life/psychology ; *Health Services Needs and Demand ; *Needs Assessment ; Medicine, Chinese Traditional/methods ; Interviews as Topic/methods ; }, abstract = {BACKGROUND: Amyotrophic Lateral Sclerosis (ALS) is a progressive and fatal neurodegenerative disorder that significantly impacts individuals and families. Previous research on ALS has predominantly focused on its pathophysiology, genetic factors, and potential therapeutic interventions. While these aspects are essential for understanding and treating the disease, there has been a growing recognition of the importance of studying patients' actual needs. Understanding these needs is vital for developing patient-centered care models that can enhance the well-being of ALS patients. However, existing studies on patients' needs are often limited in scope. Many are conducted in Western countries, and the results may not be directly applicable to patients in other cultural and socioeconomic contexts. China, with its large population and diverse cultural, economic, and healthcare landscapes, presents a unique setting for studying ALS patients' needs. At the same time, traditional Chinese medicine (TCM) practices are deeply ingrained in their healthcare system and may affect the way people with ALS seek treatment and manage their condition. Therefore, these differences may lead to differences in the actual needs of ALS patients in China. In conclusion, this qualitative study on the actual needs of ALS patients in China aims to bridge the gap in the existing research. By exploring these needs, it can provide valuable insights for healthcare providers, policymakers, and researchers, ultimately contributing to the improvement of care and quality of life for ALS patients in China.

METHOD: We carried out a qualitative study using an empirical phenomenological approach. Individual in-depth interviews were performed among 22 people with ALS from the motor neuron disease rehabilitation center of a tertiary Chinese medicine hospital in China, and the interview content was analyzed qualitatively. Interview recordings were converted to text content by NVivo 11.0 software and analyzed using Colaizzi's phenomenological method.

RESULT: Three main themes were identified in this study: (1) Demand for healthcare services, (2) Emotional requirements, (3) Functional requirements. In addition, 8 sub-themes were extracted as the actual needs of ALS patients.

CONCLUSION: This study is based on the real experience of ALS patients after diagnosis, and a deep understanding of these experiences can explore the actual needs of patients from many aspects and give reasonable advice and help. Given the particularity of the disease and the uncertainty of treatment, patients will have practical needs for relevant medical support, emotional requirements, physical functions, and other aspects during the period of illness, and the corresponding support is an effective measure to reduce the burden on patients.}, } @article {pmid39986312, year = {2025}, author = {Mizielinska, S and Hautbergue, GM and Gendron, TF and van Blitterswijk, M and Hardiman, O and Ravits, J and Isaacs, AM and Rademakers, R}, title = {Amyotrophic lateral sclerosis caused by hexanucleotide repeat expansions in C9orf72: from genetics to therapeutics.}, journal = {The Lancet. Neurology}, volume = {24}, number = {3}, pages = {261-274}, pmid = {39986312}, issn = {1474-4465}, support = {U19 AG063911/AG/NIA NIH HHS/United States ; P01 NS084974/NS/NINDS NIH HHS/United States ; P30 AG062677/AG/NIA NIH HHS/United States ; UG3 NS103870/NS/NINDS NIH HHS/United States ; RF1 NS123052/NS/NINDS NIH HHS/United States ; R01 NS117461/NS/NINDS NIH HHS/United States ; R01 NS121125/NS/NINDS NIH HHS/United States ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/therapy/diagnosis ; C9orf72 Protein/genetics ; *DNA Repeat Expansion/genetics ; }, abstract = {GGGGCC repeat expansions in C9orf72 are a common genetic cause of amyotrophic lateral sclerosis in people of European ancestry; however, substantial variability in the penetrance of the mutation, age at disease onset, and clinical presentation can complicate diagnosis and prognosis. The repeat expansion is bidirectionally transcribed in the sense and antisense directions into repetitive RNAs and translated into dipeptide repeat proteins, and both accumulate in the cortex, cerebellum, and the spinal cord. Furthermore, neuropathological aggregates of phosphorylated TDP-43 are observed in motor cortex and other cortical regions, and in the spinal cord of patients at autopsy. C9orf72 repeat expansions can also cause frontotemporal dementia. The GGGGCC repeat induces a complex interplay of loss-of-function and gain-of-function pathological mechanisms. Clinical trials using antisense oligonucleotides to target the GGGGCC repeat RNA have not been successful, potentially because they only target a single gain-of-function mechanism. Novel therapeutic approaches targeting the DNA repeat expansion, multiple repeat-derived RNA species, or downstream targets of TDP-43 dysfunction are, however, on the horizon, together with the development of diagnostic and prognostic biomarkers.}, } @article {pmid39985864, year = {2025}, author = {Wilk, LS and Hoveling, RJM and van Velthoven, MFAM and Nijs, HGT and Aalders, MCG}, title = {Optimizing the detection and characterization of bruises using multispectral imaging.}, journal = {Journal of forensic and legal medicine}, volume = {111}, number = {}, pages = {102811}, doi = {10.1016/j.jflm.2025.102811}, pmid = {39985864}, issn = {1878-7487}, mesh = {Humans ; *Contusions/pathology/diagnostic imaging ; Algorithms ; Photography ; *Hematoma/diagnostic imaging/pathology ; }, abstract = {The detection and visualization of sub-dermal hematoma (bruises) plays a key role in suspected physical abuse cases, as it aids in the evaluation of both victim and suspect statements. Current methods rely on visual inspection, frequently aided by alternate light sources (ALS). Ideally, ALS increase visual contrast by exploiting differences in light absorption (due to the formation and clearance of chromophores within the bruise). However, in practice the achievable contrast is often limited by light-scattering: the short-wavelength region of the spectrum (comprising most of the chromophore-specific absorption peaks), is also strongly scattered by the dermal tissue. This, in turn, limits achievable penetration depths, effectively obscuring deep-lying bruises. ALS-based contrast enhancement is further complicated by bruise healing; diffusion and enzymatic activity alter the chromophore concentrations as well as their 3D-distribution within the tissue. To overcome these critical limitations, we employ a multi-spectral camera (8 wavelengths simultaneously) in conjunction with both observer-based scoring and a contrast-quantification algorithm to determine the optimal wavelength for the detection and characterization of bruises over time. We show that (i) bruise contrast significantly increases at 480 nm, 620 nm and 850 nm and (ii) the wavelength achieving optimal contrast gradually changes from 850 nm to 578 nm-480 nm as the bruise heals.}, } @article {pmid39985812, year = {2025}, author = {Filippi, M and Ghirelli, A and Spinelli, EG and Agosta, F}, title = {A comprehensive update on neuroimaging endpoints in amyotrophic lateral sclerosis.}, journal = {Expert review of neurotherapeutics}, volume = {25}, number = {4}, pages = {397-413}, doi = {10.1080/14737175.2025.2470324}, pmid = {39985812}, issn = {1744-8360}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnostic imaging/physiopathology/therapy ; *Neuroimaging/methods ; Magnetic Resonance Imaging/methods ; Positron-Emission Tomography/methods ; Disease Progression ; Biomarkers ; }, abstract = {INTRODUCTION: There are currently few treatments approved for amyotrophic lateral sclerosis (ALS). Additionally, there remains a significant unmet need for reliable, standardized biomarkers to assess endpoints in clinical trials. Magnetic resonance imaging (MRI)- and positron emission tomography (PET)-derived metrics could help in patient selection and stratification, shortening trial duration and reducing costs.

AREAS COVERED: This review focuses on the potential use of neuroimaging endpoints in the context of ALS therapeutic trials, providing insights on structural and functional neuroimaging, plexus and muscle alterations, glial involvement and neuroinflammation, envisioning how these surrogates of disease progression could be implemented in clinical trials. A PubMed search covering the past 15 years was performed.

EXPERT OPINION: Neuroimaging is essential in understanding ALS pathophysiology, aiding in disease progression tracking and evaluating therapeutic interventions. High costs, limited accessibility, lack of standardization, and patient tolerability limit their use in routine ALS care. Addressing these obstacles is essential for fully harnessing neuroimaging potential in improving diagnostics and treatment in ALS.}, } @article {pmid39985309, year = {2025}, author = {Lajoie, I and , and Kalra, S and Dadar, M}, title = {Regional Cerebral Atrophy Contributes to Personalized Survival Prediction in Amyotrophic Lateral Sclerosis: A Multicentre, Machine Learning, Deformation-Based Morphometry Study.}, journal = {Annals of neurology}, volume = {97}, number = {6}, pages = {1144-1157}, pmid = {39985309}, issn = {1531-8249}, support = {//Fondation Brain Canada/ ; //ALS Society of Canada/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/mortality/diagnostic imaging/pathology ; Male ; Female ; Atrophy/pathology ; Middle Aged ; Magnetic Resonance Imaging/methods ; Aged ; *Machine Learning ; Gray Matter/diagnostic imaging/pathology ; *Brain/pathology/diagnostic imaging ; White Matter/diagnostic imaging/pathology ; Disease Progression ; }, abstract = {OBJECTIVE: Accurate personalized survival prediction in amyotrophic lateral sclerosis is essential for effective patient care planning. This study investigates whether grey and white matter changes measured by magnetic resonance imaging can improve individual survival predictions.

METHODS: We analyzed data from 178 patients with amyotrophic lateral sclerosis and 166 healthy controls in the Canadian Amyotrophic Lateral Sclerosis Neuroimaging Consortium study. A voxel-wise linear mixed-effects model assessed disease-related and survival-related atrophy detected through deformation-based morphometry, controlling for age, sex, and scanner variations. Additional linear mixed-effects models explored associations between regional imaging and clinical measurements, and their associations with time to the composite outcome of death, tracheostomy, or permanent assisted ventilation. We evaluated whether incorporating imaging features alongside clinical data could improve the performance of an individual survival distribution model.

RESULTS: Deformation-based morphometry uncovered distinct voxel-wise atrophy patterns linked to disease progression and survival, with many of these regional atrophies significantly associated with clinical manifestations of the disease. By integrating regional imaging features with clinical data, we observed a substantial enhancement in the performance of survival models across key metrics. Our analysis identified specific brain regions, such as the corpus callosum, rostral middle frontal gyrus, and thalamus, where atrophy predicted an increased risk of mortality.

INTERPRETATION: This study suggests that brain atrophy patterns measured by deformation-based morphometry provide valuable insights beyond clinical assessments for prognosis. It offers a more comprehensive approach to prognosis and highlights brain regions involved in disease progression and survival, potentially leading to a better understanding of amyotrophic lateral sclerosis. ANN NEUROL 2025;97:1144-1157.}, } @article {pmid39985291, year = {2025}, author = {Steinfurth, L and Grehl, T and Weyen, U and Kettemann, D and Steinbach, R and Rödiger, A and Grosskreutz, J and Petri, S and Boentert, M and Weydt, P and Bernsen, S and Walter, B and GüNTHER, R and Lingor, P and Koch, JC and Baum, P and Weishaupt, JH and Dorst, J and Koc, Y and Cordts, I and Vidovic, M and Norden, J and Schumann, P and Körtvélyessy, P and Spittel, S and Münch, C and Maier, A and Meyer, T}, title = {Self-assessment of amyotrophic lateral sclerosis functional rating scale on the patient's smartphone proves to be non-inferior to clinic data capture.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {26}, number = {5-6}, pages = {495-506}, doi = {10.1080/21678421.2025.2468404}, pmid = {39985291}, issn = {2167-9223}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/psychology/physiopathology ; Male ; *Smartphone ; Female ; Middle Aged ; Aged ; *Mobile Applications ; *Self-Assessment ; Disease Progression ; Severity of Illness Index ; Cohort Studies ; }, abstract = {OBJECTIVE: To investigate self-assessment of the amyotrophic lateral sclerosis functional rating scale-revised (ALSFRS-R) using the patient's smartphone and to analyze non-inferiority to clinic assessment.

METHODS: In an observational study, ALSFRS-R data being remotely collected on a mobile application (App-ALSFRS-R) were compared to ALSFRS-R captured during clinic visits (clinic-ALSFRS-R). ALS progression rate (ALSPR)-as calculated by the monthly decline of ALSFRS-R-and its intrasubject variability (ALSPR-ISV) between ratings were used to compare both cohorts. To investigate non-inferiority of App-ALSFRS-R data, a non-inferiority margin was determined.

RESULTS: A total of 691 ALS patients using the ALS-App and 1895 patients with clinic assessments were included. Clinical characteristics for the App-ALSFRS-R and clinic-ALSFRS-R cohorts were as follows: Mean age 60.45 (SD 10.43) and 63.69 (SD 11.30) years (p < 0.001), disease duration 38.7 (SD 37.68) and 56.75 (SD 54.34) months (p < 0.001) and ALSPR 0.72 and 0.59 (p < 0.001), respectively. A paired sample analysis of ALSPR-ISV was applicable for 398 patients with clinic as well as app assessments and did not show a significant difference (IQR 0.12 [CI 0.11, 0.14] vs 0.12 [CI 0.11, 0.14], p = 0.24; Cohen's d = 0.06). CI of IQR for App-ALSFRS-R was below the predefined non-inferiority margin of 0.15 IQR, demonstrating non-inferiority.

CONCLUSIONS: Patients using a mobile application for remote digital self-assessment of the ALSFRS-R revealed younger age, earlier disease course, and faster ALS progression. The finding of non-inferiority of App-ALSFRS-R assessments underscores, that data collection using the ALS-App on the patient's smartphone can serve as additional source of ALSFRS-R in ALS research and clinical practice.}, } @article {pmid39985110, year = {2025}, author = {Swanson, MEV and Mrkela, M and Turner, C and Curtis, MA and Faull, RLM and Walker, AK and Scotter, EL}, title = {Neuronal TDP-43 aggregation drives changes in microglial morphology prior to immunophenotype in amyotrophic lateral sclerosis.}, journal = {Acta neuropathologica communications}, volume = {13}, number = {1}, pages = {39}, pmid = {39985110}, issn = {2051-5960}, mesh = {*Amyotrophic Lateral Sclerosis/pathology/metabolism ; *Microglia/pathology/metabolism ; *DNA-Binding Proteins/metabolism/genetics ; Animals ; Humans ; Male ; Female ; Mice ; Middle Aged ; Aged ; Mice, Transgenic ; Immunophenotyping ; Disease Models, Animal ; Antigens, CD/metabolism ; *Motor Cortex/pathology/metabolism ; Antigens, Differentiation, Myelomonocytic/metabolism ; Calcium-Binding Proteins/metabolism ; Microfilament Proteins/metabolism ; Aged, 80 and over ; }, abstract = {Microglia are the innate immune cells of the brain with the capacity to react to damage or disease. Microglial reactions can be characterised in post-mortem tissues by assessing their pattern of protein expression, or immunophenotypes, and cell morphologies. We recently demonstrated that microglia have a phagocytic immunophenotype in early-stage ALS but transition to a dysfunctional immunophenotype by end stage, and that these states are driven by TAR DNA-binding protein 43 (TDP-43) aggregation in the human brain. However, it remains unclear how microglial morphologies are changed in ALS. Here we examine the relationship between microglial immunophenotypes and morphologies, and TDP-43 pathology in motor cortex tissue from people with ALS and from a TDP-43-driven ALS mouse model. Post-mortem human brain tissue from 10 control and 10 ALS cases was analysed alongside brain tissue from the bigenic NEFH-tTA/tetO-hTDP-43∆NLS (rNLS) mouse model of ALS at distinct disease stages. Sections were immunohistochemically labelled for microglial markers (HLA-DR, CD68, and Iba1) and phosphorylated TDP-43 (pTDP-43). Single-cell microglial HLA-DR, CD68, and Iba1 average intensities, and morphological features (cell body area, process number, total outgrowth, and branch number) were measured using custom image analysis pipelines. In human ALS motor cortex, we identified a significant change in microglial morphologies from ramified to hypertrophic, which was associated with increased Iba1 and CD68 levels. In the rNLS mouse motor cortex, the microglial morphologies changed from ramified to hypertrophic and increased Iba1 levels occurred in parallel with pTDP-43 aggregation, prior to increases in CD68 levels. Overall, the evidence presented in this study demonstrates that microglia change their morphologies prior to immunophenotype changes. These morphological changes may prime microglia near neurons with pTDP-43 aggregation for phagocytosis, in turn triggering immunophenotype changes; first, to a phagocytic state then to a dysfunctional one.}, } @article {pmid39984353, year = {2025}, author = {Comini, L and Di Pietro, DA and Olivares, A and Bertella, E and Vitacca, M}, title = {Gut dysbiosis and leaky gut syndrome in moderately impaired amyotrophic lateral sclerosis patients.}, journal = {European journal of internal medicine}, volume = {136}, number = {}, pages = {150-152}, doi = {10.1016/j.ejim.2025.02.019}, pmid = {39984353}, issn = {1879-0828}, } @article {pmid39982984, year = {2025}, author = {Verde, EM and Antoniani, F and Mediani, L and Secco, V and Crotti, S and Ferrara, MC and Vinet, J and Sergeeva, A and Yan, X and Hoege, C and Stuani, C and Paron, F and Kao, TT and Shrivastava, R and Polanowska, J and Bailly, A and Rosa, A and Aronica, E and Goswami, A and Shneider, N and Hyman, AA and Buratti, E and Xirodimas, D and Franzmann, TM and Alberti, S and Carra, S}, title = {SUMO2/3 conjugation of TDP-43 protects against aggregation.}, journal = {Science advances}, volume = {11}, number = {8}, pages = {eadq2475}, pmid = {39982984}, issn = {2375-2548}, mesh = {Humans ; *Small Ubiquitin-Related Modifier Proteins/metabolism/genetics ; *DNA-Binding Proteins/metabolism/chemistry/genetics ; *Protein Aggregates ; Protein Inhibitors of Activated STAT/metabolism/genetics ; *Ubiquitins/metabolism/genetics ; Oxidative Stress ; Sumoylation ; Stress Granules/metabolism ; *Protein Aggregation, Pathological/metabolism ; Protein Binding ; Poly-ADP-Ribose Binding Proteins ; }, abstract = {Cytosolic aggregation of the RNA binding protein TDP-43 (transactive response DNA-binding protein 43) is a hallmark of amyotrophic lateral sclerosis and frontotemporal dementia. Here, we report that during oxidative stress, TDP-43 becomes SUMO2/3-ylated by the SUMO E3 ligase protein PIAS4 (protein inhibitor of activated STAT 4) and enriches in cytoplasmic stress granules (SGs). Upon pharmacological inhibition of TDP-43 SUMO2/3-ylation or PIAS4 depletion, TDP-43 enrichment in SGs is accompanied by irreversible aggregation. In cells that are unable to assemble SGs, SUMO2/3-ylation of TDP-43 is strongly impaired, supporting the notion that SGs are compartments that promote TDP-43 SUMO2/3-ylation during oxidative stress. Binding of TDP-43 to UG-rich RNA antagonizes PIAS4-mediated SUMO2/3-ylation, while RNA dissociation promotes TDP-43 SUMO2/3-ylation. We conclude that SUMO2/3 protein conjugation is a cellular mechanism to stabilize cytosolic RNA-free TDP-43 against aggregation.}, } @article {pmid39982687, year = {2025}, author = {Loher, P and Londin, E and Ilieva, H and Pasinelli, P and Rigoutsos, I}, title = {Re-Analyses of Samples From Amyotrophic Lateral Sclerosis Patients and Controls Identify Many Novel Small RNAs With Diagnostic And Prognostic Potential.}, journal = {Molecular neurobiology}, volume = {62}, number = {7}, pages = {8135-8149}, pmid = {39982687}, issn = {1559-1182}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/diagnosis/blood ; Prognosis ; Male ; Female ; Case-Control Studies ; Middle Aged ; *MicroRNAs/genetics/blood ; Biomarkers/blood ; RNA, Ribosomal/genetics/blood ; Aged ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a highly heterogeneous disease for which accurate diagnostic and prognostic biomarkers are needed. Toward this goal, we reanalyzed two published collections of datasets generated from the plasma and serum of ALS patients and controls. We profiled these datasets for isoforms of microRNAs (miRNAs) known as isomiRs, transfer RNA-derived fragments (tRFs), and ribosomal RNA-derived fragments (rRFs), placing all remaining reads into a group labeled "not-itrs." We found that plasma and serum are rich in isomiRs (canonical, non-canonical, and non-templated), tRFs, rRFs, and members of an emerging class of small RNAs known as Y RNA-derived fragments (yRFs). In both analyzed collections, we found many isomiRs, tRFs, rRFs, and yRFs that are differentially abundant between patients and controls. We also performed a survival analysis that considered Riluzole treatment status, demographics (age at onset, age at enrollment, sex), and disease characteristics (ALSFRS, rD50, onset type) and found many of the differentially abundant small RNAs to be associated with survival time, with some of these associations being independent of Riluzole treatment. Unexpectedly, many not-itrs that did not map to the human genome mapped exactly to sequences from the SILVA database of ribosomal DNAs (rDNAs). Not-itrs from the plasma datasets mapped primarily to rDNAs from the order of Burkholderiales, and several of them were associated with patient survival. Not-itrs from the serum datasets also showed support for rDNA from Burkholderiales but a stronger support for rDNAs from the fungi group of the Nucletmycea taxon. The findings suggest that many previously unexplored small non-coding RNAs, including human isomiRs, tRFs, rRFs, and yRFs, could potentially serve as novel diagnostic and prognostic biomarkers for ALS.}, } @article {pmid39982214, year = {2025}, author = {Peng, T and Hu, N and Huang, L and Kang, Y and Yan, Y and Zhang, H and Wan, D and Jin, X and Yang, Y}, title = {Safety of edaravone in real-world use: analysis based on FDA adverse event reporting system.}, journal = {Expert opinion on drug safety}, volume = {}, number = {}, pages = {1-9}, doi = {10.1080/14740338.2025.2470874}, pmid = {39982214}, issn = {1744-764X}, abstract = {BACKGROUND: Edaravone is a novel free radical scavenger utilized to treat amyotrophic lateral sclerosis (ALS). However, long-term safety data remain limited.

RESEARCH DESIGN AND METHODS: Adverse event reports related to edaravone from the second quarter of 2017 to the second quarter of 2024 were extracted from the US Food and Drug Administration (FDA) Adverse Event Reporting System database (FAERS). Disproportionality analysis was conducted utilizing the reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and multi-item gamma Poisson shrinker (MGPS) algorithms.

RESULTS: A total of 3,149 adverse event reports related to edaravone were analyzed. The most common adverse reactions included systemic disorders and administration site reactions, nervous system disorders, respiratory system disorders, and surgical and medical procedures. New adverse reaction signals included disseminated intravascular coagulation, gastric fistula, sputum retention, excessive salivation, fractures, elevated cystatin C. The median onset time for adverse events was 43 days (interquartile range: 7-173 days).

CONCLUSION: This study confirmed previously reported adverse events and identified several new ones associated with edaravone. These findings provide valuable insights for optimizing ALS patient management and highlight the need for further research into the mechanisms of these adverse reactions.}, } @article {pmid39981400, year = {2025}, author = {Yang, EJ and Lee, SH}, title = {Herbal Medicine Extracts Improve Motor Function by Anti-Inflammatory Activity in hSOD1[G93A] Animal Model.}, journal = {Mediators of inflammation}, volume = {2025}, number = {}, pages = {1999953}, pmid = {39981400}, issn = {1466-1861}, mesh = {Animals ; Mice ; Mice, Transgenic ; *Anti-Inflammatory Agents/therapeutic use/pharmacology ; Disease Models, Animal ; *Amyotrophic Lateral Sclerosis/drug therapy/metabolism ; *Plant Extracts/therapeutic use/pharmacology ; Muscle, Skeletal/drug effects/metabolism ; Motor Neurons/drug effects/metabolism ; Oxidative Stress/drug effects ; *Herbal Medicine ; Male ; Superoxide Dismutase-1/metabolism/genetics ; Spinal Cord/drug effects/metabolism ; Inflammation/drug therapy ; Paeonia/chemistry ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a multicomplex neurodegenerative disorder characterized by motor neuron death, muscle atrophy, and respiratory failure. Owing to its multicomplex mechanisms and multifactorial nature in the skeletal muscle and spinal cord (SC), no effective therapy has been developed. However, herbal medicines, known for their multitarget properties, have demonstrated promising efficacy with limited side effects in treating various diseases. Specifically, Paeonia lactiflora Pallas has been demonstrated to exhibit analgesic, antidepressant, anti-inflammatory, and neuroprotective effects. However, the pharmacological mechanisms underlying the beneficial effects of P. lactiflora in hSOD1[G93A] animal models remain unexplored. Therefore, this study was conducted to investigate the multitarget effects of P. lactiflora in hSOD1[G93A] transgenic mice, an ALS model. Footprint tests, western blot assays, and immunohistochemical analysis were used to assess the effect of P. lactiflora on the tibia anterior (TA), gastrocnemius (GC), and SC. The results revealed that P. lactiflora augmented motor function and decreased motor neuron loss in hSOD1[G93A] mice. Furthermore, P. lactiflora significantly lowered the expression of proteins associated with inflammation and oxidative stress in the skeletal muscle (TA and GC) and SC. P. lactiflora also regulated autophagy function by reducing the levels of key markers, such as P62/sequestosome 1 (SQSTM1), microtubule-associated proteins 1A/1B light chain 3B, and SMAD family member 2, in the muscle and SC. Overall, P. lactiflora treatment improved motor function, prevented motor neuron death, and exhibited anti-inflammatory and antioxidative effects in the skeletal muscle and SC of ALS mouse models. These results suggest that P. lactiflora could serve as a promising multitarget therapeutic agent for systemic and multipathological diseases.}, } @article {pmid39981199, year = {2025}, author = {Kiernan, MC}, title = {Recent developments in consensus diagnostic criteria for amyotrophic lateral sclerosis.}, journal = {eNeurologicalSci}, volume = {38}, number = {}, pages = {100559}, pmid = {39981199}, issn = {2405-6502}, } @article {pmid39980944, year = {2025}, author = {Ji, J}, title = {To the Editor: In Response to Park et al's Perspective on the Resignation of South Korean Residents: A Medical Student View.}, journal = {Journal of graduate medical education}, volume = {17}, number = {1}, pages = {113-114}, pmid = {39980944}, issn = {1949-8357}, } @article {pmid39980027, year = {2025}, author = {Jin, Y and Conneely, KN and Ma, W and Naviaux, RK and Siddique, T and Allen, EG and Guingrich, S and Pascuzzi, RM and Jin, P}, title = {Whole-genome bisulfite sequencing of cell-free DNA unveils age-dependent and ALS-associated methylation alterations.}, journal = {Cell & bioscience}, volume = {15}, number = {1}, pages = {26}, pmid = {39980027}, issn = {2045-3701}, support = {P50 HD104458/HD/NICHD NIH HHS/United States ; R35 NS111602/NS/NINDS NIH HHS/United States ; NS111602/NS/NINDS NIH HHS/United States ; HD104458//National Institute of Child Health and Human Development/ ; }, abstract = {BACKGROUND: Cell-free DNA (cfDNA) in plasma carries epigenetic signatures specific to tissue or cell of origin. Aberrant methylation patterns in circulating cfDNA have emerged as valuable tools for noninvasive cancer detection, prenatal diagnostics, and organ transplant assessment. Such epigenetic changes also hold significant promise for the diagnosis of neurodegenerative diseases, which often progresses slowly and has a lengthy asymptomatic period. However, genome-wide cfDNA methylation changes in neurodegenerative diseases remain poorly understood.

RESULTS: We used whole-genome bisulfite sequencing (WGBS) to profile age-dependent and ALS-associated methylation signatures in cfDNA from 30 individuals, including young and middle-aged controls, as well as ALS patients with matched controls. We identified 5,223 age-related differentially methylated loci (DMLs) (FDR < 0.05), with 51.6% showing hypomethylation in older individuals. Our results significantly overlapped with age-associated CpGs identified in a large blood-based epigenome-wide association study (EWAS). Comparing ALS patients to controls, we detected 1,045 differentially methylated regions (DMRs) in gene bodies, promoters, and intergenic regions. Notably, these DMRs were linked to key ALS-associated pathways, including endocytosis and cell adhesion. Integration with spinal cord transcriptomics revealed that 31% of DMR-associated genes exhibited differential expression in ALS patients compared to controls, with over 20 genes significantly correlating with disease duration. Furthermore, comparison with published single-nucleus RNA sequencing (snRNA-Seq) data of ALS demonstrated that cfDNA methylation changes reflects cell-type-specific gene dysregulation in the brain of ALS patients, particularly in excitatory neurons and astrocytes. Deconvolution of cfDNA methylation profiles suggested altered proportions of immune and liver-derived cfDNA in ALS patients.

CONCLUSIONS: cfDNA methylation is a powerful tool for assessing age-related changes and ALS-specific molecular dysregulation by revealing perturbed locus, genes, and the proportional contributions of different tissues/cells to the plasma. This technique holds promise for clinical application in biomarker discovery across a broad spectrum of neurodegenerative disorders.}, } @article {pmid39979261, year = {2025}, author = {Liu, D and Webber, HC and Bian, F and Xu, Y and Prakash, M and Feng, X and Yang, M and Yang, H and You, IJ and Li, L and Liu, L and Liu, P and Huang, H and Chang, CY and Liu, L and Shah, SH and La Torre, A and Welsbie, DS and Sun, Y and Duan, X and Goldberg, JL and Braun, M and Lansky, Z and Hu, Y}, title = {Optineurin-facilitated axonal mitochondria delivery promotes neuroprotection and axon regeneration.}, journal = {Nature communications}, volume = {16}, number = {1}, pages = {1789}, pmid = {39979261}, issn = {2041-1723}, support = {R01 EY034353/EY/NEI NIH HHS/United States ; P30 EY026877/EY/NEI NIH HHS/United States ; 1F32EY029567//U.S. Department of Health & Human Services | NIH | National Eye Institute (NEI)/ ; EY026877//U.S. Department of Health & Human Services | NIH | National Eye Institute (NEI)/ ; EY034353//U.S. Department of Health & Human Services | NIH | National Eye Institute (NEI)/ ; S10 OD025091/OD/NIH HHS/United States ; R01 EY032518/EY/NEI NIH HHS/United States ; EY032518//U.S. Department of Health & Human Services | NIH | National Eye Institute (NEI)/ ; R01 EY023295/EY/NEI NIH HHS/United States ; EY023295//U.S. Department of Health & Human Services | NIH | National Eye Institute (NEI)/ ; F32 EY029567/EY/NEI NIH HHS/United States ; R01 EY032159/EY/NEI NIH HHS/United States ; R01 EY024932/EY/NEI NIH HHS/United States ; EY024932//U.S. Department of Health & Human Services | NIH | National Eye Institute (NEI)/ ; R01 EY025295/EY/NEI NIH HHS/United States ; S10 OD030452/OD/NIH HHS/United States ; }, mesh = {Animals ; *Mitochondria/metabolism ; *Axons/metabolism/physiology ; Membrane Transport Proteins/metabolism ; Retinal Ganglion Cells/metabolism/pathology ; Cell Cycle Proteins ; Mice ; Humans ; Microtubules/metabolism ; *Nerve Regeneration/physiology ; *Neuroprotection ; Optic Nerve/metabolism/pathology ; Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology ; *Transcription Factor TFIIIA/metabolism/genetics ; Disease Models, Animal ; Axonal Transport ; Low Tension Glaucoma/genetics/metabolism/pathology ; Motor Neurons/metabolism ; Mice, Inbred C57BL ; Male ; }, abstract = {Optineurin (OPTN) mutations are linked to amyotrophic lateral sclerosis (ALS) and normal tension glaucoma (NTG), but a relevant animal model is lacking, and the molecular mechanisms underlying neurodegeneration are unknown. We find that OPTN C-terminus truncation (OPTN∆C) causes late-onset neurodegeneration of retinal ganglion cells (RGCs), optic nerve (ON), and spinal cord motor neurons, preceded by a decrease of axonal mitochondria in mice. We discover that OPTN directly interacts with both microtubules and the mitochondrial transport complex TRAK1/KIF5B, stabilizing them for proper anterograde axonal mitochondrial transport, in a C-terminus dependent manner. Furthermore, overexpressing OPTN/TRAK1/KIF5B prevents not only OPTN truncation-induced, but also ocular hypertension-induced neurodegeneration, and promotes robust ON regeneration. Therefore, in addition to generating animal models for NTG and ALS, our results establish OPTN as a facilitator of the microtubule-dependent mitochondrial transport necessary for adequate axonal mitochondria delivery, and its loss as the likely molecular mechanism of neurodegeneration.}, } @article {pmid39978484, year = {2025}, author = {Hülsmeier, AJ}, title = {Glycosphingolipids in neurodegeneration - Molecular mechanisms, cellular roles, and therapeutic perspectives.}, journal = {Neurobiology of disease}, volume = {207}, number = {}, pages = {106851}, doi = {10.1016/j.nbd.2025.106851}, pmid = {39978484}, issn = {1095-953X}, mesh = {Humans ; *Glycosphingolipids/metabolism ; *Neurodegenerative Diseases/metabolism/pathology/therapy ; Animals ; }, abstract = {Neurodegenerative diseases, including Alzheimer's (AD), Parkinson's (PD), Huntington's (HD), and amyotrophic lateral sclerosis (ALS), are characterized by progressive neuronal loss and pose significant global health challenges. Glycosphingolipids (GSLs), critical components of neuronal membranes, regulate signal transduction, membrane organization, neuroinflammation, and lipid raft functionality. This review explores GSL roles in neural development, differentiation, and neurogenesis, along with their dysregulation in neurodegenerative diseases. Aberrations in GSL metabolism drive key pathological features such as protein aggregation, neuroinflammation, and impaired signaling. Specific GSLs, such as GM1, GD3, and GM3, influence amyloid-beta aggregation in AD, α-synuclein stability in PD, and mutant huntingtin toxicity in HD. Therapeutic strategies targeting GSL metabolism, such as GM1 supplementation and enzyme modulation, have demonstrated potential to mitigate disease progression. Further studies using advanced lipidomics and glycomics may support biomarker identification and therapeutic advancements. This work aims to highlight the translational potential of GSL research for diagnosing and managing devastating neurodegenerative conditions.}, } @article {pmid39977838, year = {2025}, author = {Chang, JH and Tschannen, D}, title = {An Integrative Review of Quality Improvement Competence and Engagement Among Frontline Nurses.}, journal = {Journal of nursing care quality}, volume = {40}, number = {2}, pages = {173-180}, pmid = {39977838}, issn = {1550-5065}, mesh = {Humans ; *Quality Improvement ; *Clinical Competence/standards ; Leadership ; *Nursing Staff, Hospital ; }, abstract = {BACKGROUND: Nurses providing direct care have firsthand knowledge of gaps in practice and thus must actively engage in quality improvement (QI) to enhance patient outcomes.

PURPOSE: This integrative review evaluated QI competence and engagement among frontline nurses.

METHODS: Using Souza et al's 6-step framework, literature on QI engagement and competence was synthesized using a rigorous search strategy and quality assessment.

RESULTS: Sixteen studies revealed generally low QI engagement and competence. Factors such as education, experience, and role influenced engagement, with higher levels of education and experience linked to higher QI involvement. Nurse leaders had higher engagement, underscoring the need for strong leadership in creating a culture of improvement.

CONCLUSIONS: Successful and sustainable QI programs and supportive environments enhance QI engagement and competence among frontline nurses.}, } @article {pmid39976286, year = {2025}, author = {Guo, K and Savelieff, MG and Jang, DG and Teener, SJ and Zhao, L and Hur, J and Goutman, SA and Feldman, EL}, title = {Longitudinal Metabolomics in Amyotrophic Lateral Sclerosis Implicates Impaired Lipid Metabolism.}, journal = {Annals of neurology}, volume = {98}, number = {1}, pages = {19-34}, pmid = {39976286}, issn = {1531-8249}, support = {UL1 TR000433/TR/NCATS NIH HHS/United States ; //the Scott L. Pranger ALS Clinic Fund/ ; //the Peter R. Clark Fund for ALS Research/ ; //the Dr. Randall Whitcomb Fund for ALS Genetics/ ; K23 ES027221/ES/NIEHS NIH HHS/United States ; //the Coleman Therapeutic Discovery Fund/ ; R01ES030049/ES/NIEHS NIH HHS/United States ; R01 ES030049/ES/NIEHS NIH HHS/United States ; UL1TR002240//National Center for Advancing Translational Sciences at the National Institutes of Health/ ; R01TS000289/CC/CDC HHS/United States ; R01 NS127188/NS/NINDS NIH HHS/United States ; K23ES027221/ES/NIEHS NIH HHS/United States ; R01NS127188/NS/NINDS NIH HHS/United States ; R01 TS000289/TS/ATSDR CDC HHS/United States ; UL1TR000433//Michigan Institute for Clinical and Health Research/ ; //the Robert A. Epstein and Joan M. Chernoff-Epstein Emerging Scholar Fund/ ; UL1 TR002240/TR/NCATS NIH HHS/United States ; //the Sinai Medical Staff Foundation/ ; //the A. Alfred Taubman Medical Research Institute/ ; //the NeuroNetwork for Emerging Therapies, University of Michigan/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism ; Male ; *Metabolomics ; Female ; *Lipid Metabolism/physiology ; Middle Aged ; Longitudinal Studies ; Aged ; Spinal Cord/metabolism ; Disease Progression ; Motor Cortex/metabolism ; *Metabolome ; }, abstract = {OBJECTIVE: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by altered metabolome and energy homeostasis, manifesting with body mass index changes and hypermetabolism-both prognostic of disease progression and survival. The cross-sectional ALS metabolome has been characterized, but longitudinal correlations to functional decline are lacking.

METHODS: We longitudinally evaluated metabolomes from ALS plasma and terminal postmortem spinal cord and brain motor cortex tissue. We constructed 3 plasma models. A linear mixed effects model correlated all metabolite levels across all timepoints to their corresponding functional scores. An interaction model predicted a longitudinal change in function from baseline metabolites, whereas a progression model identified metabolites linked to a 20% or 50% drop in function. In postmortem samples, differential metabolites in onset versus second spinal cord segments served as a surrogate of disease progression. Mendelian randomization assessed potential causality from metabolites.

RESULTS: In plasma, all models primarily selected lipid metabolites and sub-pathways, in addition to amino acids, xenobiotics, and various less frequently selected pathways. Among lipids, fatty acids and sphingomyelins were predominant, along with plasmalogens, phosphatidylcholines, and lysophospholipids. Sex interaction findings were nominal. In the spinal cord, sphingomyelin and long-chain saturated and monounsaturated fatty acids were more abundant in the onset segment tissue, whereas phosphatidylcholines and phosphatidylethanolamines were less abundant. Mendelian randomization suggested that impaired carnitine and short chain acylcarnitine metabolism may be genetically determined in ALS, along with various antioxidant derivatives.

INTERPRETATION: Our findings suggest metabolomic changes primarily involving different lipid classes and carnitine metabolism may underscore ALS severity and progression. ANN NEUROL 2025;98:19-34.}, } @article {pmid39976261, year = {2025}, author = {Menendez-Gonzalez, M}, title = {Implementing a tridimensional diagnostic framework for personalized medicine in neurodegenerative diseases.}, journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association}, volume = {21}, number = {2}, pages = {e14591}, pmid = {39976261}, issn = {1552-5279}, support = {PI21/00467//Instituto de Salud Carlos III/ ; }, mesh = {Humans ; *Precision Medicine/methods ; *Neurodegenerative Diseases/diagnosis/genetics ; Biomarkers ; Neuroimaging ; }, abstract = {Neurodegenerative diseases (NDDs) pose a significant challenge in modern medicine due to their clinical heterogeneity, multifactorial etiologies, and frequent co-pathologies. Traditional diagnostic systems, based on clinical symptoms and post mortem findings, are limited in capturing the complex interactions among genetic, molecular, and neuroanatomical factors. This manuscript introduces a novel tridimensional diagnostic framework that integrates these factors across three key axes: etiology (genetic and environmental influences), molecular markers (primary and secondary biomarkers), and neuroanatomoclinical correlations. Through case studies, we demonstrate the framework's ability to synthesize incomplete datasets, stratify patients, and guide precision medicine. By incorporating omics technologies, neuroimaging, and AI-driven probabilistic modeling, the framework enhances diagnostic accuracy and clinical relevance. This approach may contribute to overcoming the limitations of traditional nosologies, offering a scalable and adaptable tool for both clinical practice and research and advancing the field of precision medicine in NDD management. HIGHLIGHTS: Tridimensional diagnostic system: We propose a new framework that incorporates three axes - etiology, molecular markers, and neuroanatomical-clinical correlations - to enhance diagnostic accuracy for NDDs. Personalized medicine: The tridimensional system enables the integration of genetic, molecular, and clinical data, allowing for highly personalized treatment strategies tailored to individual patients. Proteinopathies as key biomarkers: This diagnostic system emphasizes the use of primary proteinopathies (amyloid, tau, synuclein) and secondary biomarkers (eg, NfL, GFAP) to monitor disease progression and treatment efficacy. Addressing clinical heterogeneity: The framework accommodates the complexity and heterogeneity of NDDs, offering an adaptable diagnostic approach for classical conditions like Alzheimer's disease, Parkinson's disease, frontotemporal dementia, and ALS. Case studies and real-world application: Practical case studies illustrate how this system can be implemented in clinical practice, enabling the combination of DMTs with symptomatic treatments.}, } @article {pmid39976178, year = {2025}, author = {Canosa, A and Manera, U and Vasta, R and Zocco, G and Di Pede, F and Cabras, S and De Mattei, F and Palumbo, F and Iazzolino, B and Minerva, E and Sbaiz, L and Brunetti, M and Gallone, S and Grassano, M and Matteoni, E and Polverari, G and Fuda, G and Casale, F and Salamone, P and De Marco, G and Marchese, G and Moglia, C and Calvo, A and Pagani, M and Chiò, A}, title = {Brain Metabolic Features of FUS-ALS: A 2-[[18]F]FDG-PET Study.}, journal = {Annals of neurology}, volume = {97}, number = {6}, pages = {1134-1143}, pmid = {39976178}, issn = {1531-8249}, support = {//A.S.D. Polisportiva U.I.C.I Torino Onlus (Oltre la Vista, Oltre la SLA)/ ; PRIN 2017//Ministero dell'Università e della Ricerca/ ; 2017SNW5MB//Ministero dell'Università e della Ricerca/ ; //Fondation Thierry Latran (INSPIRED)/ ; RF-2016- 02362405//Ministero della Salute (The Italian Ministry of Health [Ricerca Sanitaria Finalizzata])/ ; 259867//European Commission's Health Seventh Framework Programme (FP7/2007-2013)/ ; GA101017598//Horizon 2020 Framework Programme (BRAINTEASER [Bringing Artificial Intelligence Home for a Better Care of Amyotrophic Lateral Sclerosis and Multiple Sclerosis])/ ; 101137074//Horizon 2020 Framework Programme/ ; }, mesh = {Humans ; Male ; Female ; Positron-Emission Tomography/methods ; Middle Aged ; Fluorodeoxyglucose F18 ; Aged ; *Amyotrophic Lateral Sclerosis/metabolism/diagnostic imaging/genetics ; *Brain/metabolism/diagnostic imaging ; *RNA-Binding Protein FUS/genetics/metabolism ; Adult ; Radiopharmaceuticals ; }, abstract = {OBJECTIVE: We aimed at evaluating the brain metabolic features of fused in sarcoma amyotrophic lateral sclerosis (FUS-ALS) compared with sporadic ALS (sALS), using 2-[fluorine-18] fluoro-2-deoxy-D-glucose positron emission tomography (2-[[18]F]FDG-PET).

METHODS: We employed the 2-sample t-test model of SPM12, implemented in MATLAB, to compare 12 FUS-ALS cases with 40 healthy controls (HC) and 48 sALS, randomly collected from the series of patients who underwent brain 2-[[18]F]FDG-PET at the ALS Center of Turin (Italy) at diagnosis from 2009 to 2019. In the comparisons between cases and HC, we included age at PET and sex as covariates. Because FUS-ALS usually shows early onset in spinal regions, in the comparison between FUS-ALS and sALS, we included singularly the following covariates in a second step, to evaluate the determinants of eventual metabolic differences: age at PET, sex, and onset (spinal/bulbar).

RESULTS: sALS patients showed significant relative hypometabolism in bilateral fronto-temporo-occipital cortex and right insula as compared with FUS-ALS. After adjusting for age, the relative hypometabolism remained in the bilateral precentral gyrus and in the right middle and inferior temporal gyrus. As compared with HC, FUS patients displayed a significant relative hypermetabolism in the pontobulbar region and right cerebellar tonsil, dentate nucleus, and uvula, while sALS showed relative hypometabolism in bilateral frontal and occipital cortices and in left temporal and parietal regions.

INTERPRETATION: Patients with FUS-ALS show relative preservation of motor cortex metabolism compared with those with sALS, possibly reflecting the prevalence of lower motor neuron impairment in their phenotype. Prospective studies are necessary to investigate the possible role of 2-[[18]F]FDG-PET as a biomarker to track disease spreading in clinical trials. ANN NEUROL 2025;97:1134-1143.}, } @article {pmid39975337, year = {2025}, author = {Zinn, KM and McLaren, MW and Imai, MT and Jayaram, MM and Rothstein, JD and Elrick, MJ}, title = {Enterovirus D68 2A protease causes nuclear pore complex dysfunction and motor neuron toxicity.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2025.01.23.632178}, pmid = {39975337}, issn = {2692-8205}, support = {K08 NS124989/NS/NINDS NIH HHS/United States ; }, abstract = {The picornavirus Enterovirus D68 (EV-D68) is an important pathogen associated with acute flaccid myelitis (AFM). The pathogenesis of AFM involves infection of spinal motor neurons and motor neuron death, however the mechanisms linking EV-D68 infection to selective neurotoxicity are not well understood. Dysfunction of the nuclear pore complex (NPC) has been implicated in motor neuron injury in neurodegenerative diseases such as amyotrophic lateral sclerosis, and the NPC is also modified by picornavirus proteases during the course of infection. We therefore sought to determine the impact of EV-D68 proteases on NPC structure and function and their role in motor neuron toxicity. We demonstrate widespread disruption of NPC composition by EV-D68 2A and 3C proteases via the direct cleavage of a relatively small number of nucleoporins, notably Nup98 and POM121 by 2A [pro] . Using reporter systems, we demonstrate that 2A [pro] inhibits nuclear import and export of protein cargoes and also disrupts the permeability barrier of the NPC, while having no apparent effect on RNA export. We further show that 2A [pro] is toxic to induced pluripotent stem cell derived motor neurons by demonstrating a rescue of toxicity with 2A [pro] inhibitor telaprevir at concentrations that are insufficient to inhibit viral replication. This study expands our understanding of EV-D68 neuropathogenesis and provides a rationale for targeting the NPC or 2A [pro] therapeutically in AFM.}, } @article {pmid39975323, year = {2025}, author = {Bekier, ME and Pinarbasi, E and Mesojedec, JJ and Ghaffari, L and de Majo, M and Ullian, E and Koontz, M and Coleman, S and Li, X and Tank, EMH and Waksmacki, J and Barmada, S}, title = {Nemo-like kinase disrupts nuclear import and drives TDP43 mislocalization in ALS.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {39975323}, issn = {2692-8205}, support = {UL1 TR000433/TR/NCATS NIH HHS/United States ; R44 NS124457/NS/NINDS NIH HHS/United States ; P30 AG072931/AG/NIA NIH HHS/United States ; R01 NS113943/NS/NINDS NIH HHS/United States ; R01 NS097542/NS/NINDS NIH HHS/United States ; R56 NS128110/NS/NINDS NIH HHS/United States ; }, abstract = {Cytoplasmic TDP43 mislocalization and aggregation are pathological hallmarks of amyotrophic lateral sclerosis (ALS). However, the initial cellular insults that lead to TDP43 mislocalization remain unclear. In this study, we demonstrate that Nemo-like kinase (NLK)-a proline-directed serine/threonine kinase-promotes the mislocalization of TDP43 and other RNA-binding proteins by disrupting nuclear import. NLK levels are selectively elevated in neurons exhibiting TDP43 mislocalization in ALS patient tissues, while genetic reduction of NLK reduces toxicity in human neuron models of ALS. Our findings suggest that NLK is a promising therapeutic target for neurodegenerative diseases.}, } @article {pmid39975241, year = {2025}, author = {Ghaffari, LT and Welebob, E and Boehringer, A and Cyliax, K and Pasinelli, P and Trotti, D and Haeusler, AR}, title = {Neuronal Activity-Dependent Gene Dysregulation in C9orf72 i[3]Neuronal Models of ALS/FTD Pathogenesis.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {39975241}, issn = {2692-8205}, support = {R01 NS109150/NS/NINDS NIH HHS/United States ; R01 NS114128/NS/NINDS NIH HHS/United States ; RF1 NS114128/NS/NINDS NIH HHS/United States ; }, abstract = {The GGGGCC nucleotide repeat expansion (NRE) mutation in the C9orf72 (C9) gene is the most common cause of ALS and FTD. Neuronal activity plays an essential role in shaping biological processes within both healthy and neurodegenerative disease scenarios. Here, we show that at baseline conditions, C9-NRE iPSC-cortical neurons display aberrations in several pathways, including synaptic signaling and transcriptional machinery, potentially priming diseased neurons for an altered response to neuronal stimulation. Indeed, exposure to two pathophysiologically relevant stimulation modes, prolonged membrane depolarization, or a blockade of K[+] channels, followed by RNA sequencing, induces a temporally divergent activity-dependent transcriptome of C9-NRE cortical neurons compared to healthy controls. This study provides new insights into how neuronal activity influences the ALS/FTD-associated transcriptome, offering a dataset that enables further exploration of pathways necessary for conferring neuronal resilience or degeneration.}, } @article {pmid39973992, year = {2025}, author = {Nassan, M and Ayala, IA and Sloan, J and Bonfitto, A and Stark, B and Song, S and Naymik, M and Geula, C and Gefen, T and Barbieri, E and Piras, IS and Mesulam, MM and Huentelman, MJ}, title = {The genetics of TDP43-Type-C neurodegeneration: a whole genome sequencing study.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, doi = {10.1101/2025.01.25.25320561}, pmid = {39973992}, abstract = {Frontotemporal lobar degeneration-TDP Type C (TDP-C) is a unique neurodegenerative disease that starts by attacking the anterior temporal lobe leading to language and/or behavioral syndromes. Current literature on the genetic associations of TDP-C, which we have reviewed here, is uneven and lacks a discernible corpus of robust findings. In our study, we completed genome wide hypothesis-free analyses utilizing artificial Intelligence (AI) to identify rare and common variants associated with TDP-C. We then investigated ANXA11 and TARDBP in a hypothesis-driven analysis, since it was recently shown that TDP-43 and Annexin A11 co-aggregate in all TDP-C cases. 1) Whole genome sequencing was completed to identify pathogenic rare variants prioritized with Illumina's AI-based Emedgene software on 37 confirmed or probable TDP-C cases from the Northwestern-University Cohort. 2) A genome wide association study was then completed to identify common variants associated with TDP-C cases vs 290 controls. 3) Next, common and rare variants in TARDBP, and ANXA11 were investigated in TDP-C vs controls. These analyses identified novel genetic associations between FIG4 , UBQLN2 , INPP5A , and ANXA11 with TDP-C. Of these FIG4, UBQLN2 and ANXA11 have been associated previously with Amyotrophic lateral sclerosis (ALS). To further assess the observed potential genetic overlap between ALS and TDP-C, we leveraged Mendelian randomization (MR) to assess if the ALS genetic load is associated with TDP-C risk, and found evidence supporting this association. The genetic association of ANXA11 with TDP-C is particularly interesting in view of the recently discovered role of Annexin A11 in forming heterodimers with TDP-43 in all abnormal precipitates, a feature not found in TDP-A or TDP-B, which have no similar predilection for the anterior temporal lobe. In addition to the observed overlap between ALS genetics/ genetic load and TDP-C, it is worth mentioning that FIG4, INPP5A and ANXA11 have been implicated in the inositol metabolism pathway, a feature that remains to be elucidated mechanistically. Our TDP-C genetic literature review identified a surprising paucity of neuropathologically confirmed cases in published investigations. Nonetheless, the literature offers support for some of our findings and reemphasizes the absence of dominant or major pathogenic genes for TDP-C, another feature that sets this neuropathologic entity apart from TDP-A and TDP-B.}, } @article {pmid39973136, year = {2025}, author = {Deng, FY and Zhu, GL and Ou, KL and Zhu, LH and Jia, QQ and Wang, X and Guo, MW and Li, B and Li, SH and Li, XJ and Yin, P}, title = {Ribosome-associated pathological TDP-43 alters the expression of multiple mRNAs in the monkey brain.}, journal = {Zoological research}, volume = {46}, number = {2}, pages = {263-276}, pmid = {39973136}, issn = {2095-8137}, mesh = {Animals ; *RNA, Messenger/metabolism/genetics ; *Macaca fascicularis/metabolism ; *Brain/metabolism ; *Ribosomes/metabolism ; *DNA-Binding Proteins/metabolism/genetics ; *Gene Expression Regulation/physiology ; }, abstract = {Cytoplasmic accumulation of TDP-43 is a pathological hallmark of amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases. While current studies have primarily focused on gene regulation mediated by full-length nuclear TDP-43, the potential effects of cytoplasmic TDP-43 fragments remain less explored. Our previous findings demonstrated that primate-specific cleavage of TDP-43 contributes to its cytoplasmic localization, prompting further investigation into its pathological effects. In the cynomolgus monkey brain, we observed that mutant or truncated TDP-43 was transported onto the ribosome organelle. Ribosome-associated transcriptomic analysis revealed dysregulation of apoptosis- and lysosome-related genes, indicating that cytoplasmic TDP-43 induces neurotoxicity by binding to ribosomes and disrupting mRNA expression. These findings provide mechanistic insights into the gain-of-function effects of pathological TDP-43.}, } @article {pmid39971904, year = {2025}, author = {Hossain, MA and Brahme, RR and Miller, BC and Amin, J and de Barros, M and Schneider, JL and Auclair, JR and Mattos, C and Wang, Q and Agar, NYR and Greenblatt, DJ and Manetsch, R and Agar, JN}, title = {Mass spectrometry methods and mathematical PK/PD model for decision tree-guided covalent drug development.}, journal = {Nature communications}, volume = {16}, number = {1}, pages = {1777}, pmid = {39971904}, issn = {2041-1723}, support = {R01 NS065263/NS/NINDS NIH HHS/United States ; R01NS065263//U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; 18-IIA-420//Amyotrophic Lateral Sclerosis Association (ALS Association)/ ; }, mesh = {Humans ; *Decision Trees ; *Mass Spectrometry/methods ; *Drug Development/methods ; Models, Biological ; Drug Discovery/methods ; }, abstract = {Covalent drug discovery efforts are growing rapidly but have major unaddressed limitations. These include high false positive rates during hit-to-lead identification; the inherent uncoupling of covalent drug concentration and effect [i.e., uncoupling of pharmacokinetics (PK) and pharmacodynamics (PD)]; and a lack of bioanalytical and modeling methods for determining PK and PD parameters. We present a covalent drug discovery workflow that addresses these limitations. Our bioanalytical methods are based upon a mass spectrometry (MS) assay that can measure the percentage of drug-target protein conjugation (% target engagement) in biological matrices. Further we develop an intact protein PK/PD model (iPK/PD) that outputs PK parameters (absorption and distribution) as well as PD parameters (mechanism of action, protein metabolic half-lives, dose, regimen, effect) based on time-dependent target engagement data. Notably, the iPK/PD model is applicable to any measurement (e.g., bottom-up MS and other drug binding studies) that yields % of target engaged. A Decision Tree is presented to guide researchers through the covalent drug development process. Our bioanalytical methods and the Decision Tree are applied to two approved drugs (ibrutinib and sotorasib); the most common plasma off-target, human serum albumin; three protein targets (KRAS, BTK, SOD1), and to a promising SOD1-targeting ALS drug candidates.}, } @article {pmid39971261, year = {2025}, author = {Álvarez-Aznar, A and Desai, M and Orlich, MM and Vázquez-Liébanas, E and Adams, RH and Brakebusch, C and Gaengel, K}, title = {Cdc42 is crucial for mural cell migration, proliferation and patterning of the retinal vasculature.}, journal = {Vascular pharmacology}, volume = {159}, number = {}, pages = {107472}, doi = {10.1016/j.vph.2025.107472}, pmid = {39971261}, issn = {1879-3649}, mesh = {Animals ; *Cell Movement ; *Pericytes/pathology/enzymology/metabolism ; *cdc42 GTP-Binding Protein/genetics/metabolism/deficiency ; *Cell Proliferation ; *Retinal Vessels/pathology/metabolism/growth & development ; *Myocytes, Smooth Muscle/pathology/metabolism/enzymology ; Mice, Knockout ; *Retinal Neovascularization/pathology/genetics/enzymology/metabolism/physiopathology ; *Neovascularization, Physiologic ; Signal Transduction ; Mice, Inbred C57BL ; Mice ; Muscle, Smooth, Vascular ; }, abstract = {AIMS: Mural cells constitute the outer lining of blood vessels and are essential for vascular development and function. Mural cell loss or malfunction has been associated with numerous diseases including diabetic retinopathy, stroke and amyotrophic lateral sclerosis. In this work, we investigate the role of CDC42 in mural cells in vivo, using the developing mouse retina as a model.

METHODS: In this study, we generated a mouse model for Cdc42 deletion in mural cells by crossing Pdgfrb-CreER[T2] mice with Cdc42flox/flox mice. This model (Cdc42[iΔMC]) allowed us to investigate the role of CDC42 in pericytes and smooth muscle cells in the developing and adult retinal vasculature.

RESULTS: We find that, during postnatal development, CDC42 is required in both, pericytes and smooth muscle cells to maintain proper cell morphology, mural cell coverage and distribution. During retinal angiogenesis, Cdc42-depleted pericytes lag behind the sprouting front and exhibit decreased proliferation. Consequently, capillaries at the sprouting front remain pericyte deprived, become dilated and are prone to increased vascular leakage. In addition, arteries and arterioles deviate from their normal growth directions and trajectory. While in the adult retina, mural cell coverage normalizes and pericytes adopt a normal morphology, smooth muscle cell morphologies remain abnormal and arteriolar branching angles are markedly reduced.

CONCLUSIONS: Our findings demonstrate that CDC42 is required for mural cell migration and proliferation and suggest that mural cells are essential for normal morphogenesis and patterning of the developing retinal vasculature.}, } @article {pmid39971247, year = {2025}, author = {Zhang, H and Sun, Y}, title = {Response to Chen et al's "Incorporating regional variability and demographic insights into melanoma public health strategies".}, journal = {Journal of the American Academy of Dermatology}, volume = {92}, number = {6}, pages = {e207}, doi = {10.1016/j.jaad.2025.02.029}, pmid = {39971247}, issn = {1097-6787}, } @article {pmid39971210, year = {2025}, author = {Brandstötter, C and Büssing, A and Eham, M and Littger, B and Lorenzl, S and Memmel, M and Paal, P and Bublitz, SK}, title = {Assessment of the Spiritual Needs of People With Amyotrophic Lateral Sclerosis and Their Caregivers.}, journal = {Journal of pain and symptom management}, volume = {69}, number = {5}, pages = {507-514}, doi = {10.1016/j.jpainsymman.2025.02.012}, pmid = {39971210}, issn = {1873-6513}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/psychology/therapy ; *Caregivers/psychology ; Male ; Female ; Middle Aged ; *Spirituality ; Aged ; Surveys and Questionnaires ; Germany ; *Needs Assessment ; Longitudinal Studies ; Pilot Projects ; Adult ; }, abstract = {CONTEXT: Amyotrophic Lateral Sclerosis (ALS) is a progressive and fatal neurodegenerative disorder which poses multidimensional burden to patients and caregivers.

OBJECTIVES: This study aimed to investigate spiritual needs in people with Amyotrophic Lateral Sclerosis (pALS) and their closest caregivers, and to identify factors which may contribute to these needs.

METHODS: Spiritual needs were assessed based on the Spiritual Needs Questionnaire (SpNQ) as part of a longitudinal cohort study in pALS and their closest caregivers who were included in a multiprofessional pilot project for ALS in Southern Germany with a focus on neuropalliative care.

RESULTS: About 61 pALS and 52 caregivers were assessed for their spiritual needs. We show that both pALS and their caregivers maintain stable and distinct spiritual needs over time, irrespective of age, gender, care setting, or perceived level of loneliness. While pALS emphasize generativity and inner peace needs, caregivers primarily focus on finding inner peace, which they value even more than pALS.

CONCLUSIONS: Both pALS and their caregivers have strong unmet spiritual, and particularly nonreligious needs, which should be regularly assessed by the interprofessional team. Documenting these needs is the initial step in the spiritual care process, which requires a collaborative response from the interprofessional team. All healthcare professionals involved in ALS care should be attuned to the potential for unmet spiritual needs in patients and their caregivers. Early identification of these needs can facilitate the initiation of appropriate support processes.}, } @article {pmid39969752, year = {2025}, author = {Liao, D and Zhang, Y and Li, S and Tang, H and Bai, X}, title = {miRNAs in neurodegenerative diseases: from target screening to precision therapy.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {46}, number = {6}, pages = {2393-2399}, pmid = {39969752}, issn = {1590-3478}, support = {NO.2022-CXTD-05//Sichuan Province Science and Technology Support Program/ ; }, mesh = {Humans ; *MicroRNAs/metabolism/genetics ; *Neurodegenerative Diseases/therapy/genetics/diagnosis/metabolism ; Animals ; *Precision Medicine/methods ; }, abstract = {miRNAs are critical for different disease development processes, including cell growth, signaling, apoptosis, cancer and neurodegenerative diseases. It has been shown that altered miRNA levels are associated with reactive oxygen species (ROS) formation and mitochondrial dysfunction. While mitochondrial dysfunction and ROS formation occur in many neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and multiple sclerosis, amyotrophic lateral sclerosis, miRNAs have the potential to be diagnostic biomarkers and therapeutic targets with a high degree of specificity, which is highly relevant in neurodegenerative pathologies.This paper gives a general summary of the current expression of miRNAs in neurodegenerative diseases, including miRNAs up-regulated or down-regulated in a variety of diseases, as well as the associated factors of influence. miRNAs are more like a double-edged sword, their multi-targeted role has brought light to many diseases for which there are currently no clear therapeutic options, but at the same time, their low specificity and possible side effects on the whole body should not be ignored, therefore However, at the same time, its low specificity and possible side effects on the whole body should not be ignored, therefore, more attention should be paid to the development of miRNA therapy in terms of its high efficiency, the use of carriers, and the clarification of side effects.}, } @article {pmid39969750, year = {2025}, author = {de Alcântara, C and Cruzeiro, MM and França, MC and Alencar, MA and de Araújo, CM and Camargos, ST and de Souza, LC}, title = {Cognitive and behavioral follow-up of patients with amyotrophic lateral sclerosis type 8.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {46}, number = {5}, pages = {2167-2170}, pmid = {39969750}, issn = {1590-3478}, support = {APQ-02980-17//Fundação de Amparo à Pesquisa do Estado de Minas Gerais/ ; Bolsa de Produtividade//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; }, mesh = {Humans ; Male ; *Amyotrophic Lateral Sclerosis/complications/psychology/physiopathology/genetics ; Female ; Middle Aged ; Neuropsychological Tests ; Disease Progression ; Aged ; Follow-Up Studies ; Adult ; *Cognitive Dysfunction/etiology/physiopathology ; Longitudinal Studies ; }, abstract = {BACKGROUND AND OBJECTIVE: Amyotrophic Lateral Sclerosis type 8 (ALS8) is a familial motor neuron disease caused by the VAPB p.P56S mutation. There is a lack of longitudinal studies to elucidate the cognitive and behavioral progression of this disease. We aimed to investigate the progression of cognitive performance and behavioral symptoms of ALS8 patients over time.

METHODS: The cohort was composed of 23 ALS8 patients (12 men). They underwent neuropsychological assessments in two periods of time, ranging from 24 to 48 months (mean follow-up: 33 ± 10).

RESULTS: There was mild motor and functional decline during the follow-up. There were no significant differences between the first and the second evaluation on tests of verbal fluency, executive functions, episodic memory, and facial emotion recognition. There was a decline in the Language subdomain from the Addenbrooke's Cognitive Examination-revised. Behavioural measures indicated decreasing stereotypic behaviours. Anxiety and depression symptoms remained stable. No patient developed dementia.

CONCLUSION: Cognitive decline parallels motor degeneration in ALS8, with a slow pattern of progression.}, } @article {pmid39969664, year = {2025}, author = {Irdianto, SA and Dwiranti, A and Bowolaksono, A}, title = {Extrachromosomal circular DNA: a double-edged sword in cancer progression and age-related diseases.}, journal = {Human cell}, volume = {38}, number = {2}, pages = {58}, pmid = {39969664}, issn = {1749-0774}, support = {NKB-888/UN2.RST/HKP.05.00/2024//Kementerian Riset Teknologi Dan Pendidikan Tinggi Republik Indonesia/ ; }, mesh = {Humans ; *Neoplasms/genetics/therapy/pathology ; *DNA, Circular/genetics/physiology ; Disease Progression ; *Diabetes Mellitus, Type 2/genetics ; *Aging/genetics ; *Amyotrophic Lateral Sclerosis/genetics ; Werner Syndrome/genetics ; Genomic Instability/genetics ; }, abstract = {Extrachromosomal circular DNA (eccDNA) is a fascinating form of genetic material found outside the usual chromosomal DNA in eukaryotic cells, including humans. Since its discovery in the 1960s, eccDNA has been linked to critical roles in cancer progression and age-related diseases. This review thoroughly explores eccDNA, covering its types, how it forms, and its significant impact on diseases, particularly cancer. EccDNA, especially in its extrachromosomal DNA (ecDNA) form, contributes to the genetic diversity of tumour cells, helping them evolve quickly and resist treatments. Beyond cancer, eccDNA is also connected to age-related conditions like Werner syndrome, amyotrophic lateral sclerosis (ALS), and type 2 diabetes mellitus (T2DM), where it may affect genomic stability and disease development. The potential of eccDNA as a biomarker for predicting disease outcomes and as a target for new treatments is also highlighted. This review aims to deepen our understanding of eccDNA and inspire further research into its roles in human health and disease, paving the way for innovative diagnostic and therapeutic approaches.}, } @article {pmid39969638, year = {2025}, author = {Almgren, H and Mahoney, CJ and Huynh, W and D'Souza, A and Berte, S and Lv, J and Wang, C and Kiernan, MC and Calamante, F and Tu, S}, title = {Quantifying neurodegeneration within subdivisions of core motor pathways in amyotrophic lateral sclerosis using diffusion MRI.}, journal = {Journal of neurology}, volume = {272}, number = {3}, pages = {215}, pmid = {39969638}, issn = {1432-1459}, support = {APP2029871//NHMRC/ ; 1156093//NHMRC Practitioner Fellowship/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnostic imaging/pathology ; Male ; Female ; Middle Aged ; *Pyramidal Tracts/diagnostic imaging/pathology ; *Corpus Callosum/diagnostic imaging/pathology ; Aged ; *Diffusion Magnetic Resonance Imaging/methods ; *White Matter/diagnostic imaging/pathology ; Adult ; Disease Progression ; Diffusion Tensor Imaging ; }, abstract = {BACKGROUND: Diffusion MRI is sensitive to white matter changes in amyotrophic lateral sclerosis (ALS). The current study aimed to establish disease profiles across core motor pathways, and their relevance to clinical progression in ALS.

METHODS: Sixty-five participants (ALS = 47; Control = 18) were recruited for the study. White matter integrity of motor, somatosensory, and premotor subdivisions within the corticospinal tract and corpus callosum were quantified by fibre density, fibre-bundle cross-section, structural connectivity, and fractional anisotropy. Analyses focused on identifying diffusion metrics and tract profiles sensitive to ALS pathology, and their association with clinical progression.

RESULTS: Reduced fibre density of the motor subdivision of the corpus callosum (CC) and corticospinal tract (CST) demonstrated best performance in classifying ALS from controls (area-under-curve: CCmotor = 0.81, CSTmotor = 0.76). Significant reductions in fibre density (CCmotor: p < 0.001; CSTmotor: p = 0.016), and structural connectivity (CCmotor: p = 0.008; CSTsomatosensory: p = 0.012) indicated presence of ALS pathology. Reduced fibre density & cross-section significantly correlated with severity of functional impairment (ALSFRS-R; CCmotor: r = 0.52, p = 0.019; CSTmotor: r = 0.59, p = 0.016). The largest effect sizes were generally found for motor and somatosensory subdivisions across both major white matter bundles.

CONCLUSION: Current findings suggest that ALS does not uniformly impact the corticospinal tract and corpus callosum. There is a preferential disease profile of neurodegeneration mainly impacting primary motor fibres. Microstructural white matter abnormality indicated presence of ALS pathology while macrostructural white matter abnormality was associated with severity of functional impairment. Quantification of white matter abnormality in corticospinal tract and callosal subdivisions holds translational potential as an imaging biomarker for neurodegeneration in ALS.}, } @article {pmid39969486, year = {2025}, author = {Alder, J and Chukwuma, C and Farragher, T and Holden Smith, S and Morris, R and Ealing, J and Hamdalla, H and Bentley, A and Bokhari, S and Freeman, D and Al-Chalabi, A and Rog, D and Das, J and Chaouch, A}, title = {Impact of relative deprivation and ethnicity on the incidence rate of amyotrophic lateral sclerosis.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {26}, number = {5-6}, pages = {558-565}, doi = {10.1080/21678421.2025.2465609}, pmid = {39969486}, issn = {2167-9223}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/epidemiology/ethnology ; Male ; Female ; Incidence ; Middle Aged ; Aged ; *Ethnicity/statistics & numerical data ; England/epidemiology ; Adult ; Cohort Studies ; *Social Deprivation ; Risk Factors ; White People ; Aged, 80 and over ; }, abstract = {Objective: This study assessed a sizable cohort of patients with amyotrophic lateral sclerosis (ALS) in a relatively deprived and ethnically diverse area in the northwest of England. We aimed to evaluate the interaction of relative deprivation and ethnicity with the incidence of ALS. Methods: Six hundred and ninety-three adults from Greater Manchester who were diagnosed with ALS between 1 January 2011 and 31 December 2021 were included in this study. Data were collected from electronic patient records. Relative deprivation was estimated using the Index of Multiple Deprivation 2019 and patients were divided into quartiles of deprivation in England. Ethnicity was sub-grouped into White, Southeast Asian, Black, and Other. Poisson's regression analysis was used to calculate the incidence rate and its interactions with deprivation and ethnicity. Results: 55.4% of patients were male, 95.4% were White, 57.4% were in the two most deprived quartiles, and 87.2% had died by the end of the observation period. The crude incidence rate was 2.21 cases per 100,000 (95% CI 2.00-2.40) per year. There was no difference in the adjusted incidence rates among the quartiles of deprivation, even when considering ethnicity as a confounding variable. The risk of ALS in the White population was 2.08 (95% CI 1.47-3.04) times greater than that in the non-White population. Conclusion: In our cohort, relative deprivation was not an independent risk factor for ALS. A stronger association between White ethnicity and ALS was noted. The reason for this association remains unclear, highlighting the need for more research in this field.}, } @article {pmid39967643, year = {2025}, author = {Abdel-Magid, AF}, title = {Receptor-Interacting Protein Kinase 1 (RIPK1) Inhibitors as Potential Treatment for Several Inflammatory and Neurodegenerative Diseases.}, journal = {ACS medicinal chemistry letters}, volume = {16}, number = {2}, pages = {204-206}, pmid = {39967643}, issn = {1948-5875}, abstract = {The invention in this patent application relates to 2-amino-[1,2,4]triazolo[1,5-a]pyridin derivatives represented generally herein as formula 1. These compounds have activities as receptor-interacting protein kinase 1 (RIPK1) inhibitors and may potentially provide treatment and/or prophylaxis of inflammatory and neurodegenerative diseases associated with aberrant RIPK1 activity such as ulcerative colitis, Crohn's disease, psoriasis, NASH, heart failure, multiple sclerosis, amyotrophic lateral sclerosis (ALS), and Alzheimer's disease.}, } @article {pmid39965449, year = {2025}, author = {Awasthi, S and Tiwari, PC and Awasthi, S and Dwivedi, A and Srivastava, S}, title = {Mechanistic role of proteins and peptides in Management of Neurodegenerative Disorders.}, journal = {Neuropeptides}, volume = {110}, number = {}, pages = {102505}, doi = {10.1016/j.npep.2025.102505}, pmid = {39965449}, issn = {1532-2785}, mesh = {Humans ; *Neurodegenerative Diseases/drug therapy/metabolism ; *Peptides/therapeutic use/metabolism ; Animals ; *Proteins/therapeutic use/metabolism ; }, abstract = {Proteins and peptides have emerged as significant contributors in the management of neurodegenerative disorders due to their diverse biological functions. These biomolecules influence various cellular processes, including cellular repair, inflammation reduction, and neuronal survival, which are crucial for mitigating the effects of diseases such as Alzheimer's, Parkinson's, and Amyotrophic Lateral Sclerosis (ALS). By interacting with specific cellular receptors, proteins and peptides like neurotrophic factors, cytokines, and enzyme inhibitors promote neurogenesis, reduce oxidative stress, and enhance synaptic plasticity. Nevertheless, till certain limitations and challenges do exist to deliver these fragile therapeutic bioactives. Moreover, targeted delivery systems, such as nanoparticles and biomolecular carriers, are being developed to improve the bioavailability and specificity of these protein-based therapeutics, ensuring efficient crossing of the blood-brain barrier. This review explores the mechanistic pathways through which these biomolecules act, emphasizing their potential to modify disease progression and improve the quality of life in patients with neurodegenerative conditions. Overall, proteins and peptides are not only seen as promising therapeutic agents but also as foundational tools in advancing personalized medicine in the field of neurodegenerative disorders.}, } @article {pmid39965330, year = {2025}, author = {Petro, TM and Esmael, A and Pattee, GL and Al-Sarmi, F and Chiodo, F and Agarkova, IV and Dunigan, DD and Van Etten, JL}, title = {Expression of human superoxide dismutase (SOD) 1 G93A and chlorovirus ATCV-1 SOD increases the response of macrophages to inflammatory stimulants, including ATCV-1 major capsid protein glycans.}, journal = {Immunobiology}, volume = {230}, number = {2}, pages = {152881}, doi = {10.1016/j.imbio.2025.152881}, pmid = {39965330}, issn = {1878-3279}, mesh = {Animals ; Humans ; *Macrophages/immunology/metabolism ; Mice ; *Superoxide Dismutase-1/genetics/metabolism ; *Amyotrophic Lateral Sclerosis/immunology/genetics ; *Capsid Proteins/immunology/metabolism ; Cytokines/metabolism ; RAW 264.7 Cells ; Female ; Inflammation Mediators/metabolism ; Male ; }, abstract = {One cause of familial Amyotrophic Lateral Sclerosis (ALS) is a mutation in Super Oxide Dismutase 1 (SOD1) whereby amino acid 93 is alanine instead of glycine (SOD1-G93A). Transgenic mice expressing human SOD1-G93A pathogenic variant develop motor neuron disease (MND), similar to ALS. Humans with ALS and SOD1-G93A mice have elevated production of inflammatory cytokines, such as IL-6, which may promote MND. We previously showed that infection with the Chlorovirus Acanthocystis turfacea chlorella virus 1 (ATCV-1), which encodes a SOD1, accelerates onset of MND in these mice and induces macrophages to produce high levels of IL-6. We confirm here that ALS patients compared with healthy controls have significantly elevated levels of plasma IL-6 and Interferon-gamma (IFN-γ), but not IL-17. To determine if expression of ATCV-1 SOD1 or SOD1-G93A in mouse macrophages elevates expression of inflammatory cytokines, we transfected the RAW264.7 mouse macrophage cell line with plasmids encoding ATCV-1 SOD1, wild-type human SOD1, SOD1-G93A, or an empty vector. RAW264.7 cells stably expressing wtSOD1 or G93A-SOD1 were stimulated with poly I:C and Interferon-gamma, alone, or in combination to induce inflammatory factors, such as IL-6 and Nitric Oxide (NO), anti-inflammatory factors, such as IL-10, or activation of Interferon Stimulated Response Elements (ISRE) promoters. After stimulation, production of IL-6 and NO, but not IL-10 or ISRE promoter activity was significantly higher in RAW264.7 cells expressing SOD1-G93A compared with wt SOD1. Moreover, RAW264.7 cells expressing SOD1-G93A compared with wt SOD1 produced higher levels of IL-6 and NO in response to ATCV-1 glycoproteins. Finally, transfection of plasmid encoding ATCV-1 SOD1 into RAW264.7 cells significantly increased expression of inflammatory factors in responses to poly I:C and IFN-γ, primarily in an Interferon regulatory factor 3 (IRF3) dependent fashion. These data clearly show that expression of G93A-SOD1 or ATCV-1 SOD1 in macrophages significantly elevates expression of inflammatory factors following stimulations that mimic virus infection, viral components, or T cell cytokines, thereby suggesting one mechanism by which atypical SOD1 in macrophages can contribute to ALS-MND.}, } @article {pmid39963928, year = {2025}, author = {Lomas, C and Dubey, RC and Perez-Alvarez, G and Lopez Hernandez, Y and Atmar, A and Arias, AY and Vashist, A and Aggarwal, S and Manickam, P and Lakshmana, MK and Vashist, A}, title = {Recent advances in nanotherapeutics for HIV-associated neurocognitive disorders and substance use disorders.}, journal = {Nanomedicine (London, England)}, volume = {20}, number = {6}, pages = {603-619}, pmid = {39963928}, issn = {1748-6963}, support = {R01 DA049657/DA/NIDA NIH HHS/United States ; R03 AG087475/AG/NIA NIH HHS/United States ; U01 ES033265/ES/NIEHS NIH HHS/United States ; }, mesh = {Humans ; *Substance-Related Disorders/drug therapy/therapy ; Blood-Brain Barrier/metabolism ; *Nanomedicine/methods ; *HIV Infections/complications/drug therapy ; *Nanoparticles/chemistry/therapeutic use ; Animals ; *Neurocognitive Disorders/drug therapy ; *AIDS Dementia Complex/drug therapy ; }, abstract = {Substance use disorders (SUD) and HIV-associated neurocognitive disorders (HAND) work synergistically as a significant cause of cognitive decline in adults and adolescents globally. Current therapies continue to be limited due to difficulties crossing the blood-brain barrier (BBB) leading to limited precision and effectiveness, neurotoxicity, and lack of co-treatment options for both HAND and SUD. Nanoparticle-based therapeutics have several advantages over conventional therapies including more precise targeting, the ability to cross the BBB, and high biocompatibility which decreases toxicity and optimizes sustainability. These advantages extend to other neurological disorders such as Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS). This review summarizes recent advances in nanotechnology for application to HAND, SUD, and co-treatment, as well as other neurological disorders. This review also highlights the potential challenges these therapies face in clinical translation and long-term safety.}, } @article {pmid39962920, year = {2025}, author = {}, title = {Correction to "Early Nuclear Phenotypes and Reactive Transformation in Human iPSC-Derived Astrocytes From ALS Patients With SOD1 Mutations".}, journal = {Glia}, volume = {73}, number = {5}, pages = {1107}, doi = {10.1002/glia.70003}, pmid = {39962920}, issn = {1098-1136}, } @article {pmid39962623, year = {2025}, author = {Caratelli, S and De Paolis, F and Silvestris, DA and Baldari, S and Salvatori, I and Tullo, A and Lanzilli, G and Gurtner, A and Ferri, A and Valle, C and Padovani, S and Cesarini, V and Sconocchia, T and Cifaldi, L and Arriga, R and Spagnoli, GC and Ferrone, S and Venditti, A and Rossi, P and Pesole, G and Toietta, G and Sconocchia, G}, title = {The CD64/CD28/CD3ζ chimeric receptor reprograms T-cell metabolism and promotes T-cell persistence and immune functions while triggering antibody-independent and antibody-dependent cytotoxicity.}, journal = {Experimental hematology & oncology}, volume = {14}, number = {1}, pages = {17}, pmid = {39962623}, issn = {2162-3619}, support = {TITAN 2021- ARS01_00906//European Union, European Fund for Regional Development/ ; TITAN 2021- ARS01_00906//European Union, European Fund for Regional Development/ ; Investigator Grants 2020-24440//Italian Association for Cancer Research (AIRC) Foundation/ ; }, abstract = {BACKGROUND: Recent studies have shown that CD32/CD8a/CD28/CD3ζ chimeric receptor cells directly kill breast cancer cells, suggesting the existence of cell surface myeloid FcγR alternative ligands (ALs). Here, we investigated the metabolism, ALs, cytotoxicity, and immunoregulatory functions of CD64/CD28/CD3ζ in colorectal cancer (CRC) and squamous cell carcinoma of the head and neck.

METHODS: The CD64/CD28/CD3ζ -SFG retroviral vector was used to produce viruses for T-cell transduction. T-cell expansion and differentiation were monitored via flow cytometry. Gene expression was assessed by RNA-seq. Bioenergetics were documented on a Seahorse extracellular flux analyzer. CD64/CD28/CD3ζ polarization was identified via confocal microscopy. Cytotoxicity was determined by MTT assay and bioluminescent imaging, and flow cytometry. Tridimensional antitumor activity of CD64/CD28/CD3ζ T cells was achieved by utilizing HCT116-GFP 3D spheroids via the IncuCyte S3 Live-Cell Analysis system. The intraperitoneal distribution and antitumor activity of NIR-CD64/CD28/CD3ζ and NIR-nontransduced T cells were investigated in CB17-SCID mice bearing subcutaneous FaDu Luc + cells by bioluminescent and fluorescent imaging. IFNγ was assessed by ELISA.

RESULTS: Compared to CD16/CD8a/CD28/CD3ζ T cells, CD32/CD8a/CD28/CD3ζ T cells, and non-transduced T cells, CD64/CD28/CD3ζ T cells exhibited the highest levels of cell expansion and persistence capacity. A total of 235 genes linked to cell division and 52 genes related to glycolysis were overexpressed. The glycolytic phenotype was confirmed by functional in vitro studies accompanied by preferential T-cell effector memory differentiation. Interestingly, oxamic acid was found to inhibit CD64-CR T cell proliferation, indicating the involvement of lactate. Upon CD64/CD28/CD3ζ T-cell conjugation with CRC cells, CD64/CD28/CD3ζ cells polarize at immunological synapses, leading to CRC cell death. CD64/CD28/CD3ζ T cells kill SCCHN cells, and in combination with the anti-B7-H3 mAb (376.96) or anti-EGFR mAb, these cells trigger antibody-dependent cellular cytotoxicity (ADCC) in vitro under 2D and 3D conditions. The 376.96 mAb combined with CD64/CD28/CD3ζ T cells had anti-SCCHN activity in vivo. In addition, they induce the upregulation of PD-L1 and HLA-DR expression in cancer cells via IFNγ. PD-L1 positive SCCHN cells in combination with anti-PD-L1 mAb and CD64-CR T cells were killed by ADCC, which enhanced direct cytotoxicity. These findings indicate that the glycolytic phenotype is involved in CD64-CR T cell proliferation/expansion. These cells mediate long-lasting HLA-independent cytotoxicity and ADCC in CRC and SCCHN cells.

CONCLUSIONS: CD64/CD28/CD3ζ T cells could significantly impact the rational design of personalized studies to treat CRC and SCCHN and the identification of novel FcγR ALs in cancer and healthy cells.}, } @article {pmid39961705, year = {2025}, author = {Shah, NM and Kaltsakas, G and Madden-Scott, S and Apps, C and Sheridan, S and Ramsay, M and Srivastava, S and Suh, ES and D'Cruz, R and Mackie, M and Weston, N and Hart, N and Murphy, P}, title = {Mechanical insufflation-exsufflation use in neuromuscular disease: a single centre cohort study.}, journal = {BMJ open respiratory research}, volume = {12}, number = {1}, pages = {}, pmid = {39961705}, issn = {2052-4439}, mesh = {Humans ; Middle Aged ; *Insufflation/methods ; Male ; Female ; Retrospective Studies ; *Neuromuscular Diseases/therapy/mortality ; Adult ; Aged ; *Respiratory Therapy/methods ; }, abstract = {INTRODUCTION: Mechanical insufflation-exsufflation (MIE) is a commonly used therapy to augment secretion clearance in individuals with neuromuscular disease. There are no clear evidence-based guidelines on the settings that should be used in different diagnostic groups and how they should be titrated. We report on the settings used in the largest cohort of individuals using domiciliary MIE in the literature.

METHODS: A retrospective observational study reporting on all individuals initiated on MIE for long-term domiciliary use at our centre, 2013-2019.

RESULTS: This study reports on 359 adults established on domiciliary MIE. The most common diagnostic groups were congenital neuromuscular disease (26%), spinal cord injury (23%) and amyotrophic lateral sclerosis (23%). Median age at initiation was 55 years. Median (IQR) insufflation pressure was 35 (30-40) cm H2O and exsufflation pressure was 45 (40-50) cm H2O. Inspiratory time was 2.5 (2.3-2.8) s, expiratory time was 2.7 (2.3-2.8) s, and pause between expiration and inspiration was 2.0 (1.2-2.0) s. Median (IQR) survival following the initiation of MIE was 66 (54-78) months. Increasing age and amyotrophic lateral sclerosis were significantly associated with shorter life expectancy, while the delivery of MIE via oronasal interface compared with tracheostomy was associated with longer life expectancy.

CONCLUSION: This is the largest reported cohort of adults using domiciliary MIE. The most common groups using MIE were congenital neuromuscular disease, spinal cord injury patients and amyotrophic lateral sclerosis. The range of prescribed settings is narrow, reflecting the limited evidence base in this field and the need to better understand optimal targets for titration of different MIE settings.}, } @article {pmid39961673, year = {2025}, author = {Aryapadi, V and Trivedi, J}, title = {Atypical presentation of amyotrophic lateral sclerosis with SOD1-H47R mutation.}, journal = {BMJ case reports}, volume = {18}, number = {2}, pages = {}, doi = {10.1136/bcr-2024-263293}, pmid = {39961673}, issn = {1757-790X}, mesh = {Humans ; Male ; *Amyotrophic Lateral Sclerosis/genetics/diagnosis/physiopathology ; Mutation ; *Superoxide Dismutase/genetics ; *Superoxide Dismutase-1/genetics ; }, abstract = {Traditionally, amyotrophic lateral sclerosis (ALS) is recognised as a fatal neurodegenerative disease that typically emerges in the later decades of life, with a life expectancy of 2-5 years after symptom onset. We now understand that ALS exhibits a wide phenotypic clinical spectrum, significantly influenced by genetic factors. Here, we describe a patient with familial ALS carrying a heterozygous pathogenic H47R mutation of the superoxide dismutase 1 (SOD1) gene. His clinical presentation is atypical, with a slow progressive course, lower extremity weakness, and sparing of bulbar and respiratory function, consistent with the flail leg variant of ALS. The objective of this report is to increase awareness of atypical presentations of ALS and the diagnostic challenges they pose to clinicians. In addition to a description of the clinical case, we briefly discuss the new role of gene therapy in the treatment of familial ALS with SOD1 mutations.}, } @article {pmid39961464, year = {2025}, author = {Soumya, BS and Gamit, N and Patil, M and Shreenidhi, VP and Dharmarajan, A and Warrier, S}, title = {Modeling amyotrophic lateral sclerosis with amniotic membrane-derived mesenchymal stem cells: A novel approach for disease modeling.}, journal = {Experimental cell research}, volume = {446}, number = {1}, pages = {114449}, doi = {10.1016/j.yexcr.2025.114449}, pmid = {39961464}, issn = {1090-2422}, mesh = {*Amyotrophic Lateral Sclerosis/pathology/metabolism/genetics ; *Mesenchymal Stem Cells/cytology/metabolism/pathology ; Humans ; *Amnion/cytology ; Cell Differentiation ; Motor Neurons/metabolism/pathology ; Superoxide Dismutase-1/genetics ; Animals ; Superoxide Dismutase/genetics/metabolism ; Cells, Cultured ; Disease Models, Animal ; }, abstract = {Advancement of therapeutics for neurodegenerative diseases like amyotrophic lateral sclerosis (ALS) has been predominantly hampered by the dearth of relevant disease models. Despite numerous animal models, significant challenges remain in correlating these with human disease complexities. In this study, the ALS model was created using amniotic membrane-derived mesenchymal stem cells (AM-MSCs) which were differentiated into motor neurons (MN) with specific MN induction media and transiently transfected with mutated human SOD1 G93A plasmid to induce ALS-like condition. Characterization included gene expression analysis, immunocytochemistry, flow cytometry, and Western blot. Functional assays assessed the extent of degeneration and model efficiency. AM-MSCs demonstrated multipotency and were positive for MSC markers. Upon differentiation, the expression of MN markers like MNX1, Olig2, and ChAT were found to be elevated. SOD1 G93A overexpression, downregulated MN markers, upregulated NURR1 gene, reduced acetylcholine (ACh), reduced glutathione, and elevated oxidative stress markers. This robust in-vitro ALS model derived from AM-MSCs offers an alternative to animal models to provide an efficient and cost-effective platform to conduct rapid drug screening.}, } @article {pmid39961396, year = {2025}, author = {Ferraro, PM and Mollar, E and Melissari, L and Buscema, M and Bagnoli, E and Cabona, C and Gemelli, C and Vignolo, M and Maranzana, C and Marogna, M and Ferrera, L and Beronio, A and De Michelis, C and Bergamaschi, V and Bragadin, MM and Brichetto, G and Braido, F and Rao, F}, title = {Longitudinal respiratory trajectories in motor neuron disease phenotypes: Multiparametric characterization and clinical management.}, journal = {Respiratory medicine}, volume = {239}, number = {}, pages = {108003}, doi = {10.1016/j.rmed.2025.108003}, pmid = {39961396}, issn = {1532-3064}, mesh = {Humans ; Male ; Female ; Phenotype ; Middle Aged ; *Motor Neuron Disease/physiopathology/complications/therapy ; Respiratory Function Tests/methods ; Aged ; Longitudinal Studies ; Noninvasive Ventilation/methods ; Spirometry ; *Amyotrophic Lateral Sclerosis/physiopathology/complications ; Blood Gas Analysis ; }, abstract = {BACKGROUND: Motor neuron diseases (MNDs) encompass amyotrophic lateral sclerosis (ALS), pure/predominant upper (pUMN) and lower motor neuron (pLMN) phenotypes. However respiratory studies have mainly focused on bulbar (B-ALS) and spinal (S-ALS) onset ALS, while little is known in other MNDs. In this study we therefore aimed at characterizing baseline and longitudinal patterns of respiratory involvement and their clinical management in MND patients stratified by their clinical phenotype.

METHODS: Serial pulmonary function tests (PFTs) (spirometry, arterial blood gas analysis, overnight pulse oximetry and peak cough expiratory flow) records of the MND patients hospitalized between 2020 and 2024 were reviewed. Using longitudinal examinations, deltas of variation in respiratory measures were generated and frequency and timings of non-invasive ventilation (NIV) adaptation were evaluated. Data were compared between phenotypes using the Kruskal-Wallis test with Bonferroni adjustment.

RESULTS: 42 S-ALS, 105 B-ALS, 42 pLMN and 31 pUMN patients were included. Both at baseline and longitudinally, B-ALS showed the worst respiratory parameters, followed by pLMN, S-ALS and pUMN. NIV adaptation was equally frequent between groups, but earlier in B-ALS compared to pUMN (p = 0.01). At baseline, B-ALS showed worse spirometry and PCEF only, but compared to all the other phenotypes (p from <0.0001 to 0.03). Longitudinally, they conversely exhibited more severe decline in all PFTs, but only relative to pUMN (p from 0.0009 to 0.04), with deltas of variation comparable to the ones observed in S-ALS and pLMN. Among NIV users, more severe PCEF and spirometry impairment further emerged in S-ALS compared to pUMN (p from 0.01 to 0.04).

CONCLUSIONS: We evidenced convergent trajectories of respiratory decline across B-ALS, S-ALS and pLMN, highlighting the utility of multimodal assessments for tracking progressing respiratory disturbances. These findings have potential to accelerate earlier and more tailored respiratory management across diverse MND phenotypes.}, } @article {pmid39960747, year = {2025}, author = {Turnbull, J}, title = {Platform Trials in ALS.}, journal = {JAMA}, volume = {}, number = {}, pages = {}, doi = {10.1001/jama.2025.0100}, pmid = {39960747}, issn = {1538-3598}, } @article {pmid39960672, year = {2025}, author = {Paganoni, S and Fournier, CN and Macklin, EA and Chibnik, LB and Quintana, M and Saville, BR and Detry, MA and Vestrucci, M and Marion, J and McGlothlin, A and Ajroud-Driss, S and Chase, M and Pothier, L and Harkey, BA and Yu, H and Sherman, AV and Shefner, JM and Hall, M and Kittle, G and Berry, JD and Babu, S and Andrews, J and Dagostino, D and Tustison, E and Giacomelli, E and Scirocco, E and Alameda, G and Locatelli, E and Ho, D and Quick, A and Katz, J and Heitzman, D and Appel, SH and Shroff, S and Felice, K and Maragakis, NJ and Simmons, Z and Miller, TM and Olney, N and Weiss, MD and Goutman, SA and Fernandes, JA and Jawdat, O and Owegi, MA and Foster, LA and Vu, T and Ilieva, H and Newman, DS and Arcila-Londono, X and Jackson, CE and Ladha, S and Heiman-Patterson, T and Caress, JB and Swenson, A and Peltier, A and Lewis, R and Fee, D and Elliott, M and Bedlack, R and Kasarskis, EJ and Elman, L and Rosenfeld, J and Walk, D and McIlduff, C and Twydell, P and Young, E and Johnson, K and Rezania, K and Goyal, NA and Cohen, JA and Benatar, M and Jones, V and Glass, J and Shah, J and Beydoun, SR and Wymer, JP and Zilliox, L and Nayar, S and Pattee, GL and Martinez-Thompson, J and Harvey, B and Patel, S and Mahoney, P and Duda, PW and Cudkowicz, ME and , }, title = {Efficacy and Safety of Zilucoplan in Amyotrophic Lateral Sclerosis: A Randomized Clinical Trial.}, journal = {JAMA network open}, volume = {8}, number = {2}, pages = {e2459058}, pmid = {39960672}, issn = {2574-3805}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy ; Male ; Female ; Middle Aged ; Double-Blind Method ; Aged ; Treatment Outcome ; }, abstract = {IMPORTANCE: The etiology of amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease, is unknown. However, neuroinflammation and complement activation may play a role in disease progression.

OBJECTIVE: To determine the effects of zilucoplan, an inhibitor of complement C5, in individuals with ALS.

Zilucoplan was tested as regimen A of the HEALEY ALS Platform Trial, a phase 2 to 3 multicenter, randomized, double-blind, placebo-controlled perpetual platform clinical trial with sharing of trial infrastructure and placebo data across multiple regimens. Regimen A was conducted from August 17, 2020, to May 4, 2022. A total of 162 participants were randomized to receive zilucoplan (122 [75.3%]) or regimen-specific placebo (40 [24.7%]). An additional 124 concurrently randomized participants were randomized to receive placebo in other regimens.

INTERVENTIONS: Eligible participants were randomized in a 3:1 ratio to receive zilucoplan or matching placebo within strata of edaravone and/or riluzole use for a planned duration of 24 weeks. Active drug (zilucoplan, 0.3 mg/kg) and placebo were provided for daily subcutaneous dosing.

MAIN OUTCOMES AND MEASURES: The primary end point was change in disease severity from baseline through 24 weeks as measured by the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) total score and survival, analyzed using a bayesian shared-parameter model and reported as disease rate ratio (DRR; <1 indicating treatment benefit). The study included prespecified rules for early stopping for futility. Outcome analyses were performed in the full analysis set comparing the zilucoplan group with the total shared placebo group (n = 164).

RESULTS: Among the 162 participants who were randomized (mean [SD] age, 59.6 [11.3]; 99 [61.1%] male), 115 (71.0%) completed the trial. The estimated DRR common to ALSFRS-R and survival was 1.08 (95% credible interval, 0.87-1.31; posterior probability of superiority, 0.24). The trial was stopped early for futility. No unexpected treatment-related risks were identified.

CONCLUSIONS AND RELEVANCE: In this randomized clinical trial of zilucoplan in ALS, treatment did not alter disease progression. The adaptive platform design of the HEALEY ALS Platform Trial made it possible to test a new investigational product with efficient use of time and resources.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04297683.}, } @article {pmid39959987, year = {2025}, author = {Lee, D and Shin, Y and Roh, JS and Ahn, J and Jeoong, S and Shin, SS and Yoon, M}, title = {RETRACTED: Lee et al. Lemon Balm Extract ALS-L1023 Regulates Obesity and Improves Insulin Sensitivity via Activation of Hepatic PPARα in High-Fat Diet-Fed Obese C57BL/6J Mice. Int. J. Mol. Sci. 2020, 21, 4256.}, journal = {International journal of molecular sciences}, volume = {26}, number = {4}, pages = {}, pmid = {39959987}, issn = {1422-0067}, abstract = {The journal retracts the article titled "Lemon Balm Extract ALS-L1023 Regulates Obesity and Improves Insulin Sensitivity via Activation of Hepatic PPARα in High-Fat Diet-Fed Obese C57BL/6J Mice" [...].}, } @article {pmid39958595, year = {2025}, author = {Arnold, WD and Majithia, K}, title = {Triumphs, Trials, and Future Considerations in Genetic Therapies for Hereditary Neuromuscular Diseases.}, journal = {Missouri medicine}, volume = {122}, number = {1}, pages = {46-52}, pmid = {39958595}, issn = {0026-6620}, mesh = {Humans ; *Genetic Therapy/methods/trends ; *Neuromuscular Diseases/therapy/genetics ; Muscular Dystrophy, Duchenne/therapy/genetics ; Amyotrophic Lateral Sclerosis/therapy/genetics ; Muscular Atrophy, Spinal/therapy/genetics ; Precision Medicine/methods ; }, abstract = {Neuromuscular diseases include conditions that affect the spinal motor neurons, peripheral nerves, neuromuscular junctions, and muscles, and they can result from acquired and inherited causes. The number of genetic therapies targeting the inherited causes of neuromuscular diseases has surged in the last decade. This review aims to highlight the current state of genetic therapies within the framework of precision medicine, focusing on the achievements and the gaps that remain. A major emphasis is on spinal muscular atrophy, Duchenne muscular dystrophy, and amyotrophic lateral sclerosis, as these neuromuscular diseases have seen tremendous recent advancements. We will also discuss the future considerations necessary to accelerate the development of next-generation genetic therapies and enhance therapeutic outcomes for patients with neuromuscular diseases.}, } @article {pmid39958549, year = {2025}, author = {Zhang, Y}, title = {Enhancing rectal cancer liver metastasis prediction: Magnetic resonance imaging-based radiomics, bias mitigation, and regulatory considerations.}, journal = {World journal of gastrointestinal oncology}, volume = {17}, number = {2}, pages = {102151}, pmid = {39958549}, issn = {1948-5204}, abstract = {In this article, we comment on the article by Long et al published in the recent issue of the World Journal of Gastrointestinal Oncology. Rectal cancer patients are at risk for developing metachronous liver metastasis (MLM), yet early prediction remains challenging due to variations in tumor heterogeneity and the limitations of traditional diagnostic methods. Therefore, there is an urgent need for non-invasive techniques to improve patient outcomes. Long et al's study introduces an innovative magnetic resonance imaging (MRI)-based radiomics model that integrates high-throughput imaging data with clinical variables to predict MLM. The study employed a 7:3 split to generate training and validation datasets. The MLM prediction model was constructed using the training set and subsequently validated on the validation set using area under the curve (AUC) and dollar-cost averaging metrics to assess performance, robustness, and generalizability. By employing advanced algorithms, the model provides a non-invasive solution to assess tumor heterogeneity for better metastasis prediction, enabling early intervention and personalized treatment planning. However, variations in MRI parameters, such as differences in scanning resolutions and protocols across facilities, patient heterogeneity (e.g., age, comorbidities), and external factors like carcinoembryonic antigen levels introduce biases. Additionally, confounding factors such as diagnostic staging methods and patient comorbidities require further validation and adjustment to ensure accuracy and generalizability. With evolving Food and Drug Administration regulations on machine learning models in healthcare, compliance and careful consideration of these regulatory requirements are essential to ensuring safe and effective implementation of this approach in clinical practice. In the future, clinicians may be able to utilize data-driven, patient-centric artificial intelligence (AI)-enhanced imaging tools integrated with clinical data, which would help improve early detection of MLM and optimize personalized treatment strategies. Combining radiomics, genomics, histological data, and demographic information can significantly enhance the accuracy and precision of predictive models.}, } @article {pmid39958442, year = {2025}, author = {Ozbey, D and Saribas, S and Kocazeybek, B}, title = {Gut microbiota in Crohn's disease pathogenesis.}, journal = {World journal of gastroenterology}, volume = {31}, number = {6}, pages = {101266}, pmid = {39958442}, issn = {2219-2840}, mesh = {Humans ; Colon/microbiology/pathology/immunology ; *Crohn Disease/therapy/microbiology/immunology/pathology ; Dysbiosis/therapy ; *Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome/immunology ; Ileum/microbiology/pathology/immunology ; Intestinal Mucosa/microbiology/pathology/immunology ; Treatment Outcome ; }, abstract = {Inflammatory bowel diseases (IBDs) are classified into two distinct types based on the area and severity of inflammation: Crohn's disease (CD) and ulcerative colitis. In CD, gut bacteria can infiltrate mesenteric fat, causing expansion known as creeping fat, which may limit bacterial spread and inflammation but can promote fibrosis. The gut bacteria composition varies depending on whether the colon or ileum is affected. Fecal microbiota transplantation (FMT) transfers feces from a healthy donor to restore gut microbiota balance, often used in IBD patients to reduce inflammation and promote mucosal repair. The use of FMT for CD remains uncertain, with insufficient evidence to fully endorse it as a definitive treatment. While some studies suggest it may improve symptoms, questions about the duration of these improvements and the need for repeated treatments persist. There is a pressing need for methods that provide long-term benefits, as highlighted by Wu et al's research.}, } @article {pmid39957655, year = {2025}, author = {Mombaur, B and Dias, K}, title = {Patient Navigation in Amyotrophic Lateral Sclerosis (ALS): A Potential Approach to Timely Diagnosis.}, journal = {Journal of health care for the poor and underserved}, volume = {36}, number = {1}, pages = {361-374}, doi = {10.1353/hpu.2025.a951602}, pmid = {39957655}, issn = {1548-6869}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis ; *Patient Navigation/organization & administration ; Healthcare Disparities ; }, abstract = {Amyotrophic lateral sclerosis (ALS) poses challenges for timely diagnosis due to its protean early manifestations and lack of definitive tests. This article explores how patient navigation interventions can expedite diagnosis, particularly for underserved patients who face disproportionately longer delays. Patient navigation has proven effective in reducing disparities in various diseases by providing guidance and support to patients and caregivers. It enhances awareness, facilitates communication with health care providers, and streamlines diagnosis. Drawing from literature on patient navigation in other diseases, this article proposes tailored adaptations for ALS diagnosis and addresses potential implementation barriers and strategies to overcome them. Integrating patient navigation into the ALS diagnostic pathway holds promise for improving efficiency, optimizing outcomes, and reducing health care disparities among underserved populations.}, } @article {pmid39957101, year = {2025}, author = {Kikuchi, K and Yamazaki, Y and Kanekura, K and Hayamizu, Y}, title = {Graphene Biosensor Differentiating Sensitive Interactions between Ribonucleic Acid and Dipeptide Repeats in Liquid-Liquid Phase Separation.}, journal = {ACS applied materials & interfaces}, volume = {17}, number = {8}, pages = {12765-12771}, pmid = {39957101}, issn = {1944-8252}, mesh = {*Dipeptides/chemistry ; *Biosensing Techniques/methods ; *Graphite/chemistry ; *RNA/chemistry ; Humans ; C9orf72 Protein/genetics/chemistry ; Phase Separation ; }, abstract = {Liquid-Liquid Phase Separation (LLPS) plays a crucial role in cell biology and is closely associated with neurodegenerative diseases like Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD). Recent studies connect mutations in the C9ORF72 gene to the production of arginine-rich dipeptide repeat proteins (R-DPRs), such as poly(PR) and poly(GR). These R-DPRs disrupt LLPS in membrane-less organelles (MLOs) and contribute to disease pathology. While traditional analysis techniques like nuclear magnetic resonance (NMR), fluorescence recovery after photobleaching (FRAP), and Förster resonance energy transfer (FRET) provide insights into LLPS's role in these diseases, their ability is limited in detecting weak intermolecular interactions within LLPS droplets. This study employs graphene field-effect transistors (GFETs) for their superior sensitivity in detecting these molecular interactions. We immobilized RNA (poly-A) on GFETs and measured the electrical conductivity of GFETs to characterize shifts in the voltage of the charge neutral point in GFETs, allowing for the detection of dipeptide repeat peptides, such as (PR)12, (GR)12, and R12. Our results show that interactions between peptides and RNA require a specific peptide concentration threshold and vary between peptide types. Notably, the minimal conductivity shift suggests that peptides containing proline residues exhibit a nonuniform spatial distribution during interactions with RNA on graphene surfaces. This finding indicates that peptide rigidity induced by prolines plays a vital role in these molecular interactions and their multivalent contacts with RNA, which agrees with findings reported in other recent works. The capability of GFETs to detect these interactions at nanomolar concentrations marks a significant advancement in sensitivity over existing methods. This research sheds light on the mechanisms of LLPS involving R-DPRs and opens avenues for further understanding of related neurodegenerative diseases.}, } @article {pmid39956874, year = {2025}, author = {Demaegd, KC and Kernan, A and Cooper-Knock, J and van Vugt, JJFA and Harvey, C and Moll, T and O'Brien, D and Gornall, S and Drury, L and Farhan, SMK and Dion, PA and Rouleau, GA and Western, A and Parsons, PJ and Mclean, B and Benatar, M and van den Berg, LH and Van Damme, P and Willem Dankbaar, J and Hendrikse, J and Koole, W and de Bie, C and Hobson, E and Veldink, JH and van de Warrenburg, B and Pasterkamp, RJ and van Rheenen, W and Kirby, J and Shaw, PJ and van Es, MA}, title = {An observational study of pleiotropy and penetrance of amyotrophic lateral sclerosis associated with CAG-repeat expansion of ATXN2.}, journal = {European journal of human genetics : EJHG}, volume = {}, number = {}, pages = {}, pmid = {39956874}, issn = {1476-5438}, support = {216596/Z/19/Z//Wellcome Trust (Wellcome)/ ; 899-792//Motor Neurone Disease Association (MNDA)/ ; 974-797//Motor Neurone Disease Association (MNDA)/ ; 972-797//Motor Neurone Disease Association (MNDA)/ ; U54 NS092091/NS/NINDS NIH HHS/United States ; U54 NS092091/NS/NINDS NIH HHS/United States ; }, abstract = {Spinocerebellar ataxia type 2 (SCA2) and amyotrophic lateral sclerosis (ALS) are both associated with a CAG-repeat expansion in ATXN2 and with TDP-43-positive neuronal cytoplasmic inclusions. The two disorders have been viewed as distinct entities, where an intermediate length expansion of 31-33 CAG-repeats is associated with sporadic ALS and a full length expansion of ≥34 CAG-repeats is associated with SCA2. We report the clinical phenotype of ATXN2-positive patients and their relatives, identified in three specialist ALS clinics, which force a reconsideration of this dichotomy. We also report the frequency of ATXN2 expansions in two large cohorts of ALS patients and in a population-matched cohort of controls. We report ten cases of familial ALS in which disease is associated with either an intermediate or a full-length ATXN2 CAG-repeat expansion. Pedigrees and patients feature additional phenotypes including parkinsonism, dementia and essential tremor (ET). We conclude that CAG-repeat expansions in ATXN2 exhibit pleiotropy and are associated with a disease spectrum that includes ALS, SCA2, and parkinsonism; to recognise this complexity we propose the new term 'ATXN2-related neurodegeneration'. We also observed sporadic ALS associated with full-length expansions. We conclude that ATXN2 CAG-repeat expansions, irrespective of length, should be considered a risk factor for ALS. Interrupted CAG-repeats were associated with an ALS phenotype in our data but we also identified ALS cases with uninterrupted expansions. Our findings have relevance for researchers, patients and families linked to CAG-repeat expansions in ATXN2.}, } @article {pmid39956201, year = {2025}, author = {Potestio, L and Martora, F and Megna, M}, title = {Response to Sood et al's "Real-world experience of bimekizumab for plaque psoriasis in adult patients with prior exposure to interleukin-17 inhibitors: A 16-week multicenter retrospective review".}, journal = {Journal of the American Academy of Dermatology}, volume = {92}, number = {6}, pages = {e189-e190}, doi = {10.1016/j.jaad.2024.10.129}, pmid = {39956201}, issn = {1097-6787}, } @article {pmid39956001, year = {2025}, author = {Romero-Gavilán, F and Cerqueira, A and García-Arnáez, I and Scalschi, L and Vicedo, B and Azkargorta, M and Elortza, F and Izquierdo, R and Gurruchaga, M and Goñi, I and Suay, J}, title = {Proteomic evaluation of borosilicate hybrid sol-gel coatings with osteogenic, immunomodulatory and antibacterial properties.}, journal = {Colloids and surfaces. B, Biointerfaces}, volume = {250}, number = {}, pages = {114561}, doi = {10.1016/j.colsurfb.2025.114561}, pmid = {39956001}, issn = {1873-4367}, mesh = {Humans ; Staphylococcus aureus/drug effects ; *Proteomics ; *Anti-Bacterial Agents/pharmacology/chemistry ; *Osteogenesis/drug effects ; Escherichia coli/drug effects ; *Coated Materials, Biocompatible/pharmacology/chemistry ; *Silicates/chemistry/pharmacology ; Osteoblasts/drug effects/cytology/metabolism ; Gels/chemistry ; *Immunologic Factors/pharmacology/chemistry ; Microbial Sensitivity Tests ; Surface Properties ; }, abstract = {Silica hybrid sol-gel coatings represent an interesting approach to bioactivate dental implants. Boron is known for its osteogenic, angiogenic and antibacterial functions in biomedical applications. This study describes the synthesis of a novel borosilicate hybrid sol-gel coating using a mixture of methyltrimethoxysilane, tetraethyl orthosilicate and trimethyl borate (TMB). Coatings with different amounts of boron were obtained, and their physiochemical properties were examined; in vitro tests with human osteoblasts and macrophages (THP-1) were carried out. The effects of these materials on bacteria viability were evaluated using Escherichia coli and Staphylococcus aureus. The human serum proteins adsorbed onto the coatings were analysed employing proteomic techniques. To synthesise the new materials, the appropriate sol-gel reactions were developed; boron was integrated into the silica network, and well-adhering coatings were obtained. These borosilicate coatings were non-cytotoxic, displayed osteogenic potential, and upregulated adsorption of proteins related to bone regeneration (IGF2, ALS and APOE). Boron upregulated the expression of TNF-α, INFg and TGF-β and increased the TNF-α and TGF-β cytokine production in THP-1. Moreover, the addition of boron caused downregulation of NOX2 expression. Proteomic analysis revealed that boron-doping reduced the adsorption of immunoglobulins and complement system proteins. It also caused an increase in the levels of apolipoproteins, antioxidant proteins and serum amyloid A proteins, which was in agreement with in vitro results. The coatings with 10 and 20 % TMB displayed antibacterial effect against S. aureus. The results of this study will enhance our comprehension of interactions between boron-containing biomaterials and biological systems.}, } @article {pmid39955058, year = {2025}, author = {Paul, S and Dansithong, W and Figueroa, KP and Gandelman, M and Hivare, P and Scoles, DR and Pulst, SM}, title = {Staufen2 dysregulation in neurodegenerative disease.}, journal = {The Journal of biological chemistry}, volume = {301}, number = {3}, pages = {108316}, pmid = {39955058}, issn = {1083-351X}, mesh = {Humans ; Animals ; MicroRNAs/genetics/metabolism ; *RNA-Binding Proteins/genetics/metabolism ; Mice ; *Amyotrophic Lateral Sclerosis/metabolism/genetics/pathology ; HEK293 Cells ; TOR Serine-Threonine Kinases/metabolism/genetics ; Frontotemporal Dementia/metabolism/genetics/pathology ; Spinocerebellar Ataxias/metabolism/genetics/pathology ; 3' Untranslated Regions ; *Neurodegenerative Diseases/metabolism/genetics ; *Cytoskeletal Proteins/genetics/metabolism ; Disease Models, Animal ; Stress Granules/metabolism/genetics ; }, abstract = {Staufen2 (STAU2) is an RNA-binding protein that controls mRNA trafficking and expression. Previously, we showed that its paralog, Staufen1 (STAU1), was overabundant in cellular and mouse models of neurodegenerative diseases and amyotrophic lateral sclerosis (ALS) patient spinal cord. Here, we investigated features of STAU2 that might parallel STAU1. STAU2 protein, but not mRNA, was overabundant in spinocerebellar ataxia type 2 (SCA2), ALS/frontotemporal dementia patient fibroblasts, ALS patient spinal cord tissues, and in central nervous system tissues from SCA2 and ALS animal models. Exogenous expression of STAU2 in human embryonic kidney 293 cells activated mechanistic target of rapamycin (mTOR) and stress granule formation. Targeting STAU2 by RNAi normalized mTOR in SCA2 and C9ORF72 cellular models. The microRNA miR-217, previously identified as downregulated in SCA2 mice, targets the STAU2 3'-UTR. We now demonstrate that exogenous expression of miR-217 significantly reduced STAU2 and mTOR levels in cellular models of neurodegenerative disease. These results suggest a functional link between STAU2 and mTOR signaling and identify a major role for miR-217 that could be exploited in therapeutic development.}, } @article {pmid39954969, year = {2025}, author = {Utami, KH and Morimoto, S and Mitsukura, Y and Okano, H}, title = {The roles of intrinsically disordered proteins in neurodegeneration.}, journal = {Biochimica et biophysica acta. General subjects}, volume = {1869}, number = {4}, pages = {130772}, doi = {10.1016/j.bbagen.2025.130772}, pmid = {39954969}, issn = {1872-8006}, mesh = {Humans ; *Intrinsically Disordered Proteins/metabolism ; *Neurodegenerative Diseases/metabolism/pathology ; Animals ; Proteostasis ; Autophagy ; alpha-Synuclein/metabolism ; Proteasome Endopeptidase Complex/metabolism ; }, abstract = {Neurodegenerative diseases such as Amyotrophic Lateral Sclerosis, Alzheimer's disease, Parkinson's disease, and Huntington's disease share a common pathological hallmark: the accumulation of misfolded proteins, particularly involving intrinsically disordered proteins (IDPs) like TDP-43, FUS, Tau, α-synuclein, and Huntingtin. These proteins undergo pathological aggregation, forming toxic inclusions that disrupt cellular function. The dysregulation of proteostasis mechanisms, including the ubiquitin-proteasome system (UPS), ubiquitin-independent proteasome system (UIPS), autophagy, and molecular chaperones, exacerbates these proteinopathies by failing to clear misfolded proteins effectively. Emerging therapeutic strategies aim to restore proteostasis through proteasome activators, autophagy enhancers, and chaperone-based interventions to prevent the toxic accumulation of IDPs. Additionally, understanding liquid-liquid phase separation (LLPS) and its role in stress granule dynamics offers novel insights into how aberrant phase transitions contribute to neurodegeneration. By targeting the molecular pathways involved in IDP aggregation and proteostasis regulation, and better understanding the specificity of each component, research in this area will pave the way for innovative therapeutic approaches to combat these neurodegenerative diseases. This review discusses the molecular mechanisms underpinning IDP pathology, highlights recent advancements in drug discovery, and explores the potential of targeting proteostasis machinery to develop effective therapies.}, } @article {pmid39954940, year = {2025}, author = {Satao, KS and Doshi, GM}, title = {Intercellular communication via exosomes: A new paradigm in the pathophysiology of neurodegenerative disorders.}, journal = {Life sciences}, volume = {365}, number = {}, pages = {123468}, doi = {10.1016/j.lfs.2025.123468}, pmid = {39954940}, issn = {1879-0631}, mesh = {Humans ; *Exosomes/metabolism/physiology ; *Neurodegenerative Diseases/physiopathology/metabolism/pathology ; *Cell Communication/physiology ; Animals ; }, abstract = {Neurodegenerative disorders are one of the leading causes of death and disability and pose a great economic burden on healthcare systems. Generally, these neurodegenerative disorders have a progressive deterioration in neural function and structure, and deposition of misfolded proteins commonly occurs, such as amyloid-β in AD and α-synuclein in PD. However, there exists a special class of exosomes, which acts like a transmitter and enhances communication between cells. The present review discusses the significant role of exosomes in neurodegenerative diseases, with a focus on Amyotrophic lateral Sclerosis (ALS), AD, PD, and Huntington's disease (HD). In this review, the biogenesis of exosomes is discussed from multivesicular bodies and onwards to their release into the extracellular environment. The present review focuses on recent data concerning the possible use of modified exosomes as ND therapy. Indeed, future work is needed to explain the processes driving exosome biogenesis and cargo selection, while opening new routes by the use of exosome-based therapeutics in neurodegenerative disease diagnosis and treatment.}, } @article {pmid39954710, year = {2025}, author = {Nadeem, ZA and Ahmed, S}, title = {Amyotrophic lateral sclerosis and lovastatin: a promising treatment perspective.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {26}, number = {5-6}, pages = {595-596}, doi = {10.1080/21678421.2025.2463943}, pmid = {39954710}, issn = {2167-9223}, } @article {pmid39954119, year = {2025}, author = {Jacobsen, AB and Fanella, G and de Carvalho, M and Koltzenburg, M and Oliveira Santos, M and Cengiz, B and Blicher, J and Obál, I and Heintzelmann, MB and Nix, W and Camdessanché, JP and Fuglsang-Frederiksen, A and Tankisi, H}, title = {Variability of the Penn upper motor neuron score in amyotrophic lateral sclerosis: need for a revised score.}, journal = {Journal of neurology}, volume = {272}, number = {3}, pages = {208}, pmid = {39954119}, issn = {1432-1459}, support = {R346-2020-1946//Lundbeck Foundation/ ; R392-2022-699//Lundbeck Foundation/ ; J.nr.23-2B-12533//Aage og Johanne Louis-Hansens Fond/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/physiopathology ; Male ; Female ; Aged ; Reproducibility of Results ; Middle Aged ; *Severity of Illness Index ; *Motor Neurons/pathology ; Aged, 80 and over ; Observer Variation ; }, abstract = {There is a need for a consensus on a clinical scale for evaluating upper motor neuron (UMN) burden in amyotrophic lateral sclerosis (ALS) to improve consistency in clinical diagnosis, research and monitoring of disease progression. The Penn upper motor neuron score (PUMNS) is the most commonly published scale, however, the reliability of the scale has only been evaluated in a single study involving two raters. The objective of this study was to evaluate the inter-rater reliability of the PUMNS in ALS patients among multiple raters, and to discuss an updated UMN score including the signs with the highest inter-rater reliability. This study included seven ALS patients (mean age: 71 ± 11.5, six males, one female). Each patient was evaluated with the PUMNS by eight raters from different centers blinded to previous observations. The intra-class correlation coefficient (ICC) was calculated to assess the inter-rater reliability of the total PUMNS. The inter-rater reliability of the binary subscores was assessed with Gwet's AC1 coefficient. The inter-rater agreement for the total PUMNS yielded an ICC of 0.81 (95% CI 0.56;0.96). Items with the highest inter-rater reliability included Hoffman's sign, Babinski's sign, clonus and deep tendon reflexes, while the facial reflex (Gwet's AC1 -0.038 (95% CI -0.25,0.18)) and crossed adduction (0.18 (95% CI (-0.32,0.67)) had the lowest inter-rater reliability. In conclusion, PUMNS demonstrated good inter-rater reliability overall, while some of the subscores had poor inter-rater reliability. Based on this, we call for an updated UMN score to enhance diagnostic accuracy and research consistency in ALS.}, } @article {pmid39954028, year = {2025}, author = {Al Ojaimi, Y and Vallet, N and Dangoumau, A and Lanznaster, D and Bruno, C and Lefevre, A and Osman, S and Dupuy, C and Emond, P and Vourc'h, P and Corcia, P and Krupova, Z and Veyrat-Durebex, C and Blasco, H}, title = {Metabolomic and Proteomic Profiling of Serum-Derived Extracellular Vesicles from Early-Stage Amyotrophic Lateral Sclerosis Patients.}, journal = {Journal of molecular neuroscience : MN}, volume = {75}, number = {1}, pages = {21}, pmid = {39954028}, issn = {1559-1166}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism/blood ; Male ; Female ; Middle Aged ; *Extracellular Vesicles/metabolism ; Aged ; Biomarkers/blood ; *Proteome/metabolism ; *Metabolome ; Adult ; }, abstract = {The identification of reliable biomarkers for amyotrophic lateral sclerosis (ALS) is an unmet medical need for the development of diagnostic and therapeutic strategies. Brain-derived extracellular vesicles (EVs) have been described in peripheral blood serum and used as a direct readout of the status of the central nervous system. Here, we aimed to explore exosome-enriched EVs (referred to simply as EVs) from ALS patients via omics analysis at an early disease stage. Serum EVs were obtained from 9 healthy controls and 9 ALS patients. After EV purification, proteomic (LC‒MS/MS followed by TimsTOF Pro Mass Spectrometry) and metabolomic (Q Exactive mass spectrometer) analyses were performed. No differences in the size or concentration of EVs were observed between the controls and ALS patients. Proteomic analysis revealed 45 proteins differentially expressed in the EVs of ALS patients compared with those of controls. Metabolomic analysis revealed several distinctly represented metabolites involved in the citrate cycle and complex lipid metabolism between patients and controls. Interomics correlation analysis revealed 2 modules that were strongly associated with ALS and included several lipid metabolism-related proteins and metabolites. This study is the first to evaluate EVs by integrated proteomics and metabolomics in early-stage ALS patients, highlighting the technological progress in global inter-omics explorations of small biological samples. The differences observed in the levels of several exosomal proteins and metabolites, including phospholipids, could be used to identify serum biomarkers and novel players involved in ALS pathogenesis.}, } @article {pmid39953725, year = {2025}, author = {Nishida, K and Sakashita, K and Futamura, N}, title = {Decision-making trends in therapeutic interventions for multiple system atrophy: a 24-year retrospective study.}, journal = {Movement disorders clinical practice}, volume = {12}, number = {6}, pages = {823-827}, pmid = {39953725}, issn = {2330-1619}, support = {JPMH23FC1010//the Ministry of Health, Labour and Welfare, Japan/ ; }, mesh = {Humans ; *Multiple System Atrophy/therapy ; Retrospective Studies ; Male ; Female ; Middle Aged ; *Tracheostomy/trends ; Aged ; Enteral Nutrition/trends ; Japan ; Adult ; *Respiration, Artificial/trends ; *Clinical Decision-Making ; Age Factors ; }, abstract = {BACKGROUND: Managing multiple system atrophy (MSA) is challenging. While invasive interventions for amyotrophic lateral sclerosis are well-studied, those for MSA remain less explored.

OBJECTIVES: To explore factors influencing treatment choices and trends in advanced-stage MSA.

METHODS: A retrospective cohort study analyzed 128 MSA patients at Hyogo Chuo National Hospital, Japan, from 2000 to 2024, focusing on treatment period and age at onset.

RESULTS: Tracheostomy invasive ventilation (TIV) decreased after 2014 (26.9% vs. 9.2%; P = 0.023). TIV-treated patients remained similarly young before and after 2014 (age at onset 52.7 vs. 54.5 years; P = 0.659) and tracheostomy was chosen by younger patients after 2014 (58.3 vs. 51.5 years; P < 0.001). Conversely, enteral nutrition increased in older patients (57.4 vs. 62.9 years; P = 0.011).

CONCLUSIONS: In Japanese MSA, preferences for invasive treatments shifted, with younger patients favoring TIV and tracheostomy, while older patients preferred less invasive options, emphasizing personalized care.}, } @article {pmid39952435, year = {2025}, author = {Truel, JS and Novice, M and Shapiro, J and Lo Sicco, KI}, title = {Response to Folliat et al's "Characteristics of pruritus in lichen planopilaris and frontal fibrosing alopecia: A cohort study in a French hospital".}, journal = {Journal of the American Academy of Dermatology}, volume = {92}, number = {6}, pages = {e195}, doi = {10.1016/j.jaad.2024.11.084}, pmid = {39952435}, issn = {1097-6787}, } @article {pmid39952329, year = {2025}, author = {Ji, Y and Jiang, Q and Chen, B and Chen, X and Li, A and Shen, D and Shen, Y and Liu, H and Qian, X and Yao, X and Sun, H}, title = {Endoplasmic reticulum stress and unfolded protein response: Roles in skeletal muscle atrophy.}, journal = {Biochemical pharmacology}, volume = {234}, number = {}, pages = {116799}, doi = {10.1016/j.bcp.2025.116799}, pmid = {39952329}, issn = {1873-2968}, mesh = {*Unfolded Protein Response/physiology/drug effects ; Humans ; *Endoplasmic Reticulum Stress/physiology/drug effects ; *Muscular Atrophy/metabolism/pathology ; Animals ; *Muscle, Skeletal/metabolism/pathology/drug effects ; }, abstract = {Skeletal muscle atrophy is commonly present in various pathological states, posing a huge burden on society and patients. Increased protein hydrolysis, decreased protein synthesis, inflammatory response, oxidative stress, mitochondrial dysfunction, endoplasmic reticulum stress (ERS) and unfolded protein response (UPR) are all important molecular mechanisms involved in the occurrence and development of skeletal muscle atrophy. The potential mechanisms of ERS and UPR in skeletal muscle atrophy are extremely complex and have not yet been fully elucidated. This article elucidates the molecular mechanisms of ERS and UPR, and discusses their effects on different types of muscle atrophy (muscle atrophy caused by disuse, cachexia, chronic kidney disease (CKD), diabetes mellitus (DM), amyotrophic lateral sclerosis (ALS), spinal muscular atrophy (SMA), spinal and bulbar muscular atrophy (SBMA), aging, sarcopenia, obesity, and starvation), and explores the preventive and therapeutic strategies targeting ERS and UPR in skeletal muscle atrophy, including inhibitor therapy and drug therapy. This review aims to emphasize the importance of endoplasmic reticulum (ER) in maintaining skeletal muscle homeostasis, which helps us further understand the molecular mechanisms of skeletal muscle atrophy and provides new ideas and insights for the development of effective therapeutic drugs and preventive measures for skeletal muscle atrophy.}, } @article {pmid39950184, year = {2025}, author = {Høj, A and Holm-Yildiz, S and Krag, T and Dejanovic, D and van Overeem Hansen, T and Dunø, M and Ørngreen, MC and Vissing, J and Løkken, N}, title = {2-[[18]F] FDG PET/CT in Rapid Late-Onset Multiple Acyl-CoA Dehydrogenase Deficiency: A Case Report.}, journal = {JIMD reports}, volume = {66}, number = {2}, pages = {e12469}, pmid = {39950184}, issn = {2192-8304}, abstract = {Multiple acyl-CoA dehydrogenase deficiency (MADD) is a rare inborn metabolic myopathy affecting fat and protein metabolism. Patients with late-onset MADD typically present with exercise intolerance and muscle weakness. We present a patient with an acute, very late-onset symptom debut at 52 years of age. Over 5 months, the patient deteriorated from asymptomatic to almost complete loss of ambulation. He had a substantial weight loss, head-drop, progressive proximal limb and chewing weakness. Due to the rapid progression, amyotrophic lateral sclerosis, myositis, myasthenia gravis and a paraneoplastic syndrome in relation to underlying malignancy were considered first. A 2-[[18]F] FDG PET/CT scan was performed to exclude a paraneoplastic syndrome. The scan revealed diffuse and symmetric, pathologically high 2-[[18]F] FDG-uptake in the patient's neck, shoulder, and paravertebral muscles, which was later suggested as a sign of a metabolic myopathy. Muscle biopsy (Oil Red O staining) and acylcarnitine profile (elevated C5-C18 acylcarnitines) findings suggested MADD, which was confirmed by genetic analysis showing biallelic variants in the ETFDH gene (c.1763A>G, p.(His588Arg); c.897G>A, p.(Leu299=)). After 1 month of dietary intervention and daily diet supplements (riboflavin 400 mg TID, levocarnitine 1 g TID, Q10 150 mg qD in two doses), the patient had almost recovered to his habitual level. A posttreatment muscle biopsy showed less disrupted ultrastructure of the myofibers. We learned from this case of rapid and late-onset MADD that 2-[[18]F] FDG PET/CT, with diffuse and symmetric 2-[[18]F] FDG-uptake in skeletal muscle, can be valuable in clarifying this rare diagnosis.}, } @article {pmid39949668, year = {2025}, author = {Xu, J and Yu, Y and Wang, Y and Zhang, S and Liu, E and Wang, W and Zhu, C and Li, J}, title = {Postoperative Axial Length Prediction Model in Children With Congenital Cataract and Intraocular Lens Implantation.}, journal = {Journal of ophthalmology}, volume = {2025}, number = {}, pages = {9948890}, pmid = {39949668}, issn = {2090-004X}, abstract = {Purpose: To develop a prediction model for postoperative axial length (AL) in Asian children with congenital cataracts undergoing primary/secondary intraocular lens (IOL) implantation. Design: Retrospective observational study. Methods: Data were collected from children who underwent cataract surgery for congenital cataracts at the Eye Hospital of Wenzhou Medical University between 2006 and 2020. All participants completed preoperative and at least 1-year of postoperative follow-up. SPSS 26.0 software was used to analyze the variable factors affecting AL growth and the interactions among these factors. A generalized estimating equation (GEE) was employed to assess the correlation between the AL and related univariates over time. The univariate model was applied to build a multivariate model to predict the postoperative AL. Two validation sets were used to verify the accuracy of the formula. Results: The study involved 86 children, accounting for 148 eyes. The median age at the time of surgery was 3.00 years, with a median age of 9.50 years at the final follow-up visit. The median duration of follow-up was 5.00 years. The preoperative and final follow-up mean ALs were 21.79 ± 1.77 and 23.36 ± 1.90 mm, respectively. Taking the predicted AL (Y) as the dependent variable and the age at surgery (X 1), age at review (X 2), and preoperative AL (X 3) as the independent variables, the prediction model was established as Y = 0.20 - 0.473 × X 1 + 0.446 × X 2 + 0.993 × X 3 - 0.014 × (X 2 - X 1)∗X 2. Conclusions: This model predicts AL growth in children following congenital cataract surgery and IOL implantation, helping ophthalmologists select appropriate IOL power.}, } @article {pmid39948244, year = {2025}, author = {Picard, F and Nonaka, T and Belotti, E and Osseni, A and Errazuriz-Cerda, E and Jost-Mousseau, C and Bernard, E and Conjard-Duplany, A and Bohl, D and Hasegawa, M and Raoul, C and Galli, T and Schaeffer, L and Leblanc, P}, title = {Enhanced secretion of the amyotrophic lateral sclerosis ALS-associated misfolded TDP-43 mediated by the ER-ubiquitin specific peptidase USP19.}, journal = {Cellular and molecular life sciences : CMLS}, volume = {82}, number = {1}, pages = {76}, pmid = {39948244}, issn = {1420-9071}, support = {MyoNeurALP strategic grants//AFM-Téléthon/ ; SPREADALS//Agence Nationale de la Recherche/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/metabolism/pathology/genetics ; Humans ; *Endoplasmic Reticulum/metabolism ; *DNA-Binding Proteins/metabolism/chemistry/genetics ; Protein Folding ; *Endopeptidases/metabolism/genetics ; HEK293 Cells ; rab GTP-Binding Proteins/metabolism ; HeLa Cells ; }, abstract = {Proteinopathies, such as amyotrophic lateral sclerosis (ALS), are marked by the accumulation of misfolded proteins that disrupt cellular processes. Eukaryotic cells have developed protein quality control systems to eliminate these aberrant proteins, but these systems often fail to differentiate between normal and misfolded proteins. In ALS, pathological inclusions primarily composed of misfolded TDP-43 are a hallmark of the disease. Recently, a novel unconventional secretion process called misfolding-associated protein secretion (MAPS) has been discovered to selectively export misfolded proteins. USP19, an Endoplasmic Reticulum-associated ubiquitin peptidase, plays a crucial role in this process. In this study, we investigated the impact of ER-anchored USP19 on the secretion of misfolded TDP-43. Here we found that USP19 overexpression significantly promotes the secretion of soluble and aggregated misfolded TDP-43, requiring both ER anchoring and ubiquitin peptidase activity. Characterization of the cellular and molecular mechanisms involved in this process highlighted the importance of early autophagosomal and late endosomal/amphisomal compartments, while lysosomes did not play a key role. By using dominant-negative mutants and small interfering RNAs, we identified that USP19-mediated secretion of misfolded TDP-43 is modulated by key factors involved in cellular trafficking and secretion pathways, such as ATG7, the ESCRT-O HGS/HRS, the Rab GTPases RAB11A, RAB8A, and RAB27A, and the v-SNARE VAMP7. We also confirmed the crucial role of the DNAJC5/CSPα cochaperone. Overall, this study provides new insights into how cells manage the secretion of misfolded TDP-43 proteins and potentially opens new avenues for therapeutic interventions in ALS and related disorders.}, } @article {pmid39947885, year = {2025}, author = {Iacoangeli, A and Dilliott, AA and Al Khleifat, A and Andersen, PM and Başak, NA and Cooper-Knock, J and Corcia, P and Couratier, P and deCarvalho, M and Drory, VE and Glass, JD and Gotkine, M and Lerner, YM and Hardiman, O and Landers, JE and McLaughlin, RL and Pardina, JSM and Morrison, K and Pinto, S and Povedano, M and Shaw, CE and Shaw, PJ and Silani, V and Ticozzi, N and van Damme, P and van den Berg, LH and Vourc'h, P and Weber, M and Veldink, JH and , and Dobson, R and Rouleau, GA and Al-Chalabi, A and Farhan, SMK}, title = {Oligogenic structure of amyotrophic lateral sclerosis has genetic testing, counselling and therapeutic implications.}, journal = {Journal of neurology, neurosurgery, and psychiatry}, volume = {}, number = {}, pages = {}, doi = {10.1136/jnnp-2024-335364}, pmid = {39947885}, issn = {1468-330X}, abstract = {BACKGROUND: Despite several studies suggesting a potential oligogenic risk model in amyotrophic lateral sclerosis (ALS), case-control statistical evidence implicating oligogenicity with disease risk or clinical outcomes is limited. Considering its direct clinical and therapeutic implications, we aim to perform a large-scale robust investigation of oligogenicity in ALS risk and in the disease clinical course.

METHODS: We leveraged Project MinE genome sequencing datasets (6711 cases and 2391 controls) to identify associations between oligogenicity in known ALS genes and disease risk, as well as clinical outcomes.

RESULTS: In both the discovery and replication cohorts, we observed that the risk imparted from carrying multiple ALS rare variants was significantly greater than the risk associated with carrying only a single rare variant, both in the presence and absence of variants in the most well-established ALS genes. However, in contrast to risk, the relationships between oligogenicity and ALS clinical outcomes, such as age of onset and survival, did not follow the same pattern.

CONCLUSIONS: Our findings represent the first large-scale, case-control assessment of oligogenicity in ALS and show that oligogenic events involving known ALS risk genes are relevant for disease risk in ~6% of ALS but not necessarily for disease onset and survival. This must be considered in genetic counselling and testing by ensuring to use comprehensive gene panels even when a pathogenic variant has already been identified. Moreover, in the age of stratified medication and gene therapy, it supports the need for a complete genetic profile for the correct choice of therapy in all ALS patients.}, } @article {pmid39947630, year = {2025}, author = {Moreno-Martinez, L and Gaja-Capdevila, N and Mosqueira-Martín, L and Herrando-Grabulosa, M and Rodriguez-Gomez, L and Gonzalez-Imaz, K and Calvo, AC and Sagartzazu-Aizpurua, M and Moreno-García, L and Fuentes, JM and Acevedo-Arozena, A and Aizpurua, JM and Miranda, JI and López de Munain, A and Vallejo-Illarramendi, A and Navarro, X and Osta, R and Gil-Bea, FJ}, title = {Novel FKBP prolyl isomerase 1A (FKBP12) ligand promotes functional improvement in SOD1[G93A] amyotrophic lateral sclerosis (ALS) mice.}, journal = {British journal of pharmacology}, volume = {182}, number = {11}, pages = {2466-2486}, doi = {10.1111/bph.17448}, pmid = {39947630}, issn = {1476-5381}, support = {PID2022-140354OB-I00//Agencia Estatal de Investigación/ ; PID2020-119780RB-100//Agencia Estatal de Investigación/ ; IKERBASQUE/PP/2022/003//Ikerbasque, Basque Foundation for Science/ ; PIF19/184//Euskal Herriko Unibertsitatea/ ; PI2020/08-1//CIBER-CALS/ ; CB06/05/1105//Instituto de Salud Carlos III of Spain/ ; CB06/05/0041//Instituto de Salud Carlos III of Spain/ ; BIO19/ROCHE/017/BD//Roche Stop Fuga de Cerebros/ ; IT1732-22//Basque Government/ ; }, mesh = {Animals ; *Amyotrophic Lateral Sclerosis/drug therapy/metabolism/physiopathology/genetics ; Ligands ; Mice ; *Superoxide Dismutase-1/genetics ; Mice, Transgenic ; *Tacrolimus Binding Protein 1A/metabolism ; Disease Models, Animal ; Humans ; Male ; Motor Neurons/drug effects ; Ryanodine Receptor Calcium Release Channel/metabolism ; Mice, Inbred C57BL ; }, abstract = {BACKGROUND AND PURPOSE: Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease with limited treatment options. ALS pathogenesis involves intricate processes within motor neurons, characterized by dysregulated Ca[2+] influx and buffering in early ALS-affected motor neurones. This study proposes the modulation of ryanodine receptors (RyRs), key mediators of intracellular Ca[2+], as a therapeutic target.

EXPERIMENTAL APPROACH: A novel class of novel FKBP12 ligands that show activity as cytosolic calcium modulators through stabilizing RyR channel activity, were tested in the superoxide dismutase 1 (SOD1)[G93A] mouse model of ALS. Different outcomes were used to assess treatment efficacy, including electrophysiology, histopathology, neuromuscular function and survival.

KEY RESULTS: Among the novel FKBP12 ligands, MP-010 was chosen for its central nervous system availability and favourable in vitro pharmaco-toxicological profile. Chronic administration of MP-010 to SOD1[G93A] mice produced preservation of motor nerve conduction, with the 61-mg·kg[-1] dose significantly delaying the onset of motor impairment. This was accompanied by improved motor coordination, increased innervated endplates and significant preservation of motor neurones in the spinal cord of treated mice. Notably, MP-010 treatment significantly extended lifespan by an average of 10 days compared to vehicle.

CONCLUSIONS AND IMPLICATIONS: FKBP12 ligands, particularly MP-010, exhibit promising neuroprotective effects in ALS, highlighting their potential as novel therapeutic agents. Further investigations into the molecular mechanisms and clinical translatability of these compounds are needed for their application in ALS treatment.}, } @article {pmid39947279, year = {2025}, author = {Gelbenegger, G and Cheskes, S and Jilma, B and Zeitlinger, M and Lin, S and Drennan, IR and Jorda, A}, title = {Amiodarone dose in patients with shockable out-of-hospital cardiac arrest.}, journal = {Resuscitation}, volume = {209}, number = {}, pages = {110534}, doi = {10.1016/j.resuscitation.2025.110534}, pmid = {39947279}, issn = {1873-1570}, mesh = {Humans ; *Amiodarone/administration & dosage ; *Out-of-Hospital Cardiac Arrest/therapy/mortality/drug therapy ; Male ; Female ; *Anti-Arrhythmia Agents/administration & dosage ; Aged ; Middle Aged ; *Cardiopulmonary Resuscitation/methods ; Registries ; *Electric Countershock/methods ; Dose-Response Relationship, Drug ; Treatment Outcome ; }, abstract = {BACKGROUND: Amiodarone is used in shockable out-of-hospital cardiac arrest (OHCA), but the ideal dose is unknown.

METHODS: This was an analysis from the Resuscitation Outcomes Consortium Cardiac Epidemiologic Registry (2011-2015). Patients with shockable OHCA who received 5 or more defibrillation attempts and treatment with 300 or 450 mg of amiodarone were included. Outcomes were ROSC at ED arrival, survival at hospital discharge, and favorable neurologic function at discharge. Group-differences were adjusted for using inverse probability weighting and a multiple logistic regression model.

RESULTS: The present study included 910 patients; 426 received amiodarone 300 mg and 484 received amiodarone 450 mg. The amiodarone 300 mg group had a higher estimated probability of ROSC at ED arrival as compared with the amiodarone 450 mg group (30.8% [95% CI, 26.6-35.1] vs 24.2% [95% CI, 20.5-27.9], respectively; adjusted probability difference, 6.6% (0.9-12.3), p = 0.0234). The group differences in survival at hospital discharge (21.3% [95% CI, 17.2-25.4] vs 18.0% [95% CI, 14.6-21.5]; adjusted probability difference, 3.3% [-2.3-8.8]) and favorable neurologic outcome at discharge (16.5% [95% CI, 12.9-20.2] vs 12.7% [95% CI, 9.5-16.0]; adjusted probability difference, 3.8% [95% CI, -1.2-8.7]) did not reach statistical significance.

CONCLUSION: In patients with shockable OHCA who received 5 or more defibrillation attempts, a dose of amiodarone 300 mg was associated with a similar survival compared with a total dose of amiodarone 450 mg. Further study is needed to evaluate the need for a second administration of amiodarone in patients with shockable OHCA.}, } @article {pmid39947099, year = {2025}, author = {Tan, HHG and Nitert, AD and van Veenhuijzen, K and Dukic, S and van Zandvoort, MJE and Hendrikse, J and van Es, MA and Veldink, JH and Westeneng, HJ and van den Berg, LH}, title = {Neuroimaging correlates of domain-specific cognitive deficits in amyotrophic lateral sclerosis.}, journal = {NeuroImage. Clinical}, volume = {45}, number = {}, pages = {103749}, pmid = {39947099}, issn = {2213-1582}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/complications/diagnostic imaging/pathology/physiopathology/psychology ; Male ; Female ; Middle Aged ; Magnetic Resonance Imaging/methods ; Aged ; *Cognitive Dysfunction/diagnostic imaging/etiology/physiopathology/pathology ; *Neuroimaging/methods ; Gray Matter/diagnostic imaging/pathology ; White Matter/diagnostic imaging/pathology ; Adult ; *Brain/diagnostic imaging/pathology ; Neuropsychological Tests ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with frequent extra-motor involvement. In the present study, we investigated whether specific cognitive and behavioral deficits in ALS correlate with distinct extra-motor neurodegeneration patterns on brain MRI.

METHODS: We performed multimodal brain MRI and Edinburgh cognitive and behavioral ALS screen (ECAS) in 293 patients and 237 controls. Follow-up data were acquired from 171 patients with a median duration of 7.9 months. Domain-level cognitive scores from the ECAS were compared with grey and white matter MRI parameters. Interaction analyses between patients and controls were performed to explore whether correlates were specific to ALS, rather than related to normal aging. Follow-up data were used to assess changes of domain-associated brain structures over time.

RESULTS: Language impairment was significantly associated with (left predominant) frontal, temporal, parietal and subcortical grey matter neurodegeneration. Letter fluency with widespread cortical and subcortical grey matter involvement. Memory dysfunction with hippocampal and medial-temporal atrophy. Executive impairment was exclusively correlated with widespread white matter impairment. Visuospatial scores did not correlate with MRI parameters. Interaction analyses between patients and controls showed that most ECAS-MRI correlations were stronger in ALS than in controls (75.7% significant in grey matter, 52.7% in white matter). Longitudinal analyses showed that all grey matter structures associated with cognitive domains worsened over time while, for this study population, ECAS domain scores did not decline significantly.

CONCLUSIONS: MRI can capture the heterogeneity of cognitive and behavioral involvement in ALS and provides a useful longitudinal biomarker for progression of extra-motor neurodegeneration.}, } @article {pmid39946662, year = {2025}, author = {Cordts, I and Fuetterer, C and Wachinger, A and von Heynitz, R and Kessler, T and Freigang, M and Quinten, AL and Bjelica, B and Brakemeier, S and Hobbiebrunken, E and Hagenacker, T and Petri, S and Koch, JC and Hahn, A and Lingor, P and Deschauer, M and Günther, R and Weiler, M and Haller, B and Feneberg, E}, title = {Long-Term Dynamics of CSF and Serum Neurofilament Light Chain in Adult Patients With 5q Spinal Muscular Atrophy Treated With Nusinersen.}, journal = {Neurology}, volume = {104}, number = {5}, pages = {e213371}, pmid = {39946662}, issn = {1526-632X}, mesh = {Humans ; Female ; Male ; *Neurofilament Proteins/blood/cerebrospinal fluid ; Adult ; Retrospective Studies ; *Oligonucleotides/therapeutic use ; Middle Aged ; *Muscular Atrophy, Spinal/drug therapy/cerebrospinal fluid/blood ; Biomarkers/cerebrospinal fluid/blood ; Young Adult ; }, abstract = {BACKGROUND AND OBJECTIVES: The availability of disease-modifying therapies for 5q-associated spinal muscular atrophy (SMA) has heightened the need to identify suitable biomarkers. This study investigates neurofilament light chain (NfL) concentrations during long-term nusinersen treatment in adult SMA.

METHODS: In a retrospective study of prospectively collected data, NfL concentrations in the CSF (cNfL) and serum (sNfL) were measured in patients with SMA from 8 German centers and in neurologic controls using a single-molecule array (Simoa) assay. NfL concentrations and clinical characteristics, including the clinical scores Hammersmith Functional Motor Scale Expanded (HFMSE), Revised Upper Limb Module (RULM), and Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R), were analyzed for defined treatment intervals (T1-T4 [loading phase until 4 months], T5-T8 [until 23 months], T9-T12 [until 37 months], and T13-T19 [until 60 months]). Linear mixed models with a random intercept were used to assess the changes in NfL levels during treatment, considering time and covariates as fixed effects.

RESULTS: One hundred thirteen adult patients with SMA (median age 35, 46% female), with a treatment duration of maximum 60 months, and 52 controls were included. At baseline, NfL concentrations were significantly higher in SMA {cNfL median, 585 (interquartile range [IQR] 428-787) pg/mL; sNfL, 11 (IQR 8-14) pg/mL} than in controls (cNfL, 420 [IQR 323-662] pg/mL; sNfL, 8 [IQR 6-12] pg/mL) (cNfL, p = 0.021; sNfL, p = 0.030). Median differences for all clinical scores were the highest for T5-T8 compared with the loading phase (Δ HFMSE, 0.6 [IQR 0.1-1.4], p = 0.017; Δ RULM, 0.9 [IQR 0.4-1.3], p < 0.001; Δ ALSFRS-R, 0.7 [IQR 0.4-1.0], p < 0.001), but not for subsequent intervals. Longitudinal analysis revealed a significant decrease of NfL concentrations during each treatment interval compared with the loading phase (p < 0.05, respectively) except for sNfL in T13-T19. Even among patients with no measurable clinical improvement (Δ HFMSE ≤ 0), more than 50% showed declining cNfL and sNfL levels up to T13-T19.

DISCUSSION: NfL decreased during nusinersen treatment, suggesting its potential as a pharmacodynamic response marker in adult SMA. However, in patients without detectable clinical improvement, our study cannot determine whether they represent a more sensitive outcome measure or are not clinically meaningful.}, } @article {pmid39946043, year = {2025}, author = {Patnana, DP and Kanikaram, SP and Kumar, P and Cheerala, VSK and Sivaramakrishnan, V and Tripathi, P and Chandra, BP}, title = {Simultaneous determination of polycyclic aromatic hydrocarbons, their derivatives, and phthalic acid esters bound to ambient PM2.5 during pre-summer season in Bengaluru, India, and potential effect on protein aggregation diseases.}, journal = {Environmental science and pollution research international}, volume = {32}, number = {29}, pages = {17393-17406}, pmid = {39946043}, issn = {1614-7499}, mesh = {*Polycyclic Aromatic Hydrocarbons/analysis ; *Particulate Matter ; India ; *Phthalic Acids/analysis ; Air Pollutants/analysis ; Esters ; Environmental Monitoring ; Seasons ; Humans ; Tandem Mass Spectrometry ; }, abstract = {Air pollution pertaining to particulate matter (PM) is a major issue in most of the metropolitan cities across the world. Inhalation exposure to organic species like polycyclic aromatic hydrocarbons (PAHs), derivatives of PAHs (oxygenated and nitrated PAHs), and phthalic acid esters (PAEs) bound to PM is of major concern owing to its carcinogenic, mutagenic, and endocrine disrupting nature. In this study for the first time, we report a total of 22 aromatic organic species which include PAHs, derivatives of PAHs, and PAEs using an optimized high-performance liquid chromatography coupled to the tandem mass spectrometer (HPLC-MS/MS) method. Further, this optimized method was used to carry out the measurements of the 22 targeted organic constituents bound to the ambient fine particulate matter (PM2.5) collected in Bengaluru, a metropolitan city in India as a part of a pilot study during the pre-summer season. Among the reported compounds, benzo[b]fluoranthene (3.82 ng m[-3]), 9-nitroanthracene (10.47 ng m[-3]), and diethyl phthalate (5.38 ng m[-3]) are the most abundant PAHs, the derivatives of PAHs, and PAEs, respectively. Determined diagnostic ratios of PAHs have shown that the sampling site is majorly influenced by traffic emissions. Benzo[a]pyrene, a Group 1 carcinogen has occasionally exceeded the limits set by National Ambient Air Quality Standards (NAAQs), India during the sampling period. Further, a preliminary study was performed using a yeast model of amyotrophic lateral sclerosis (ALS) expressing transactive response DNA binding protein 43 (TDP43) and we demonstrated that commonly reported organics such as PAHs and PAEs bound to PM2.5 have induced significantly elevated aggregation in wild type TDP43. Preliminary results of this study indicate that there is a need for further detailed health risk assessment due to inhalation exposure of organic constituents bound to the ambient PM in Bengaluru.}, } @article {pmid39945358, year = {2025}, author = {Badger, SE and Coldicott, I and Kyrgiou-Balli, E and Higginbottom, A and Moutin, C and Mohd Imran, K and Day, JC and Cooper-Knock, J and Mead, RJ and Alix, JJP}, title = {A bacterial artificial chromosome mouse model of amyotrophic lateral sclerosis manifests 'space cadet syndrome' on two FVB backgrounds.}, journal = {Disease models & mechanisms}, volume = {18}, number = {2}, pages = {}, pmid = {39945358}, issn = {1754-8411}, support = {Alix/Apr19/871-791/MNDA_/Motor Neurone Disease Association/United Kingdom ; //University of Sheffield/ ; }, mesh = {Animals ; *Amyotrophic Lateral Sclerosis/genetics/physiopathology/pathology ; Disease Models, Animal ; *Chromosomes, Artificial, Bacterial/genetics ; Mice, Transgenic ; C9orf72 Protein/metabolism ; *Frontotemporal Dementia/genetics/physiopathology/pathology ; Phenotype ; *Genetic Background ; Mice ; Seizures/complications/pathology/physiopathology ; }, abstract = {C9orf72-related amyotrophic lateral sclerosis (ALS)/frontotemporal dementia (FTD) has proven difficult to model in mice. Liu et al. (2016) reported a bacterial artificial chromosome (BAC) transgenic mouse displaying behavioural, motor and pathological abnormalities. This was followed by multiple laboratories independently refuting and confirming phenotypes. A proposed explanation centred on the use of different FVB background lines (from The Jackson Laboratory and Janvier Labs). We studied C9orf72 BAC mice on both backgrounds and found significantly elevated levels of dipeptide repeat proteins, but no evidence of a transgene-associated phenotype. We observed seizures and a gradual decline in functional performance in transgenic and non-transgenic mice, irrespective of genetic background. The phenotype was in keeping with the so-called 'space cadet syndrome'. Our findings indicate that the differences previously reported are not due to C9orf72 status and highlight the importance of using genetic backgrounds that do not confound interpretation of neurodegenerative phenotypes.}, } @article {pmid39944773, year = {2025}, author = {Cheng, R and Dimitriou, D and Yao, G and Li, X and Lv, X and Yang, Y and Ying, H and Wang, Z and Tsai, TY}, title = {Outperformance of Combined Artificial Anterolateral Ligament and ACL Reconstruction Compared With Isolated Artificial ACL Reconstruction in Knees With Anterolateral Structure and ACL Deficiency: A Biomechanical Analysis.}, journal = {Orthopaedic journal of sports medicine}, volume = {13}, number = {2}, pages = {23259671241309270}, pmid = {39944773}, issn = {2325-9671}, abstract = {BACKGROUND: Despite the promising clinical outcomes of artificial polyethylene terephthalate (PET) ligaments in isolated anterior cruciate ligament reconstruction (ACLR), their biomechanical performance after combined anterolateral ligament reconstruction (ALLR)/ACLR in anterolateral structure (ALS)/anterior cruciate ligament (ACL)-deficient knees has not been investigated.

PURPOSE/HYPOTHESIS: The purpose of this study was to compare biomechanical performance in cadaveric knees between combined artificial ALLR/ACLR and isolated artificial ACLR using PET ligaments. It was hypothesized that combined artificial ALLR/ACLR would restore native knee stability and outperform isolated artificial ACLR in ALS/ACL-deficient knees.

STUDY DESIGN: Controlled laboratory study.

METHODS: Eight fresh-frozen cadaveric knees were tested using a robotic manipulator. Each knee was tested in 4 states: (1) ALS/ACL intact, (2) ALS/ACL deficient, (3) ACLR, and (4) ALLR/ACLR. The anterior tibial translation (ATT) and tibial internal rotation (IR) in each knee condition were measured under 3 loads: (1) 89 N of anterior tibial loading, (2) 5 N·m of IR torque, and (3) simulated pivot shift (combined 5 N·m of IR torque and 7 N·m of valgus load).

RESULTS: During 89 N of anterior tibial loading, there were no significant differences in ATT between the isolated ACLR and ALLR/ACLR knees. During 5 N·m of IR torque, the mean tibial IR at 45° of flexion was significantly higher in the ACLR knees (32.49°± 7.96°) than in the ALLR/ACLR knees (21.78°± 3.03°) (P < .05). During the simulated pivot shift, the mean ATT and tibial IR at 30° and 45° of flexion were significantly higher in the ACLR knees (ATT: 5.09 ± 2.74 mm at 30°, 5.43 ± 2.79 mm at 45°; IR: 30.08°± 7.31° at 30°, 32.55°± 6.48° at 45°) than in the ALLR/ACLR knees (ATT: 1.93 ± 2.71 mm at 30°, 1.17 ± 2.26 mm at 45°; IR: 22.12°± 4.05° at 30°, 22.18°± 3.37° at 45°) (P < .05).

CONCLUSION: Combined artificial ALLR/ACLR restored native knee stability across multiple flexion angles and outperformed isolated artificial ACLR in ALS/ACL-deficient knees, particularly with respect to ATT and tibial IR during the pivot-shift test.

CLINICAL RELEVANCE: The indications of the artificial PET ligament may be expanded to include combined ALLR/ACLR to restore knee stability better than isolated artificial ACLR in ALS/ACL-deficient knees.}, } @article {pmid39944166, year = {2025}, author = {Islam, S and Noorani, A and Sun, Y and Michikawa, M and Zou, K}, title = {Multi-functional role of apolipoprotein E in neurodegenerative diseases.}, journal = {Frontiers in aging neuroscience}, volume = {17}, number = {}, pages = {1535280}, pmid = {39944166}, issn = {1663-4365}, abstract = {Genetic diversity in the apolipoprotein E (ApoE) gene has been identified as the major susceptibility genetic risk factor for sporadic Alzheimer's disease (SAD). Specifically, the ApoEε4 allele is a significant risk factor for SAD, while ApoEε2 allele provides protection compared to the more common ApoEε3 allele. This review discusses the role of the ApoE in AD and other neurodegenerative disorders. ApoE, a cholesterol transport protein, influences several pathways involved in neurodegeneration, particularly in AD. Beyond its established role in amyloid β-protein (Aβ) metabolism and deposition, ApoE also impacts tau pathology, neurodegeneration, and the microglial response to AD. The review aims to provide an updated overview of ApoE's diverse roles, emphasizing its involvement in Aβ clearance through ApoE receptors. It also covers ApoE's influence in other neurodegenerative diseases like Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration (FTLD), Huntington's disease (HD), vascular dementia (VD), and multiple sclerosis (MS). New research highlights the interaction between ApoE and presenilin (PS), suggesting connections between familial AD (FAD) and SAD. The review also explores protective effects of ApoE mutations against AD and ApoE4-induced tauopathy, neurodegeneration, and neuroinflammation. The insights from this comprehensive update could indeed lead to new therapeutic strategies for neurodegenerative diseases.}, } @article {pmid39944085, year = {2025}, author = {Sakurai, H and Suzuki, M and Asakura, A}, title = {Editorial: Induced pluripotent stem cells (iPSCs) for skeletal muscle diseases.}, journal = {Frontiers in cell and developmental biology}, volume = {13}, number = {}, pages = {1556403}, pmid = {39944085}, issn = {2296-634X}, } @article {pmid39942798, year = {2025}, author = {Długosz, A and Błaszak, B and Czarnecki, D and Szulc, J}, title = {Mechanism of Action and Therapeutic Potential of Xanthohumol in Prevention of Selected Neurodegenerative Diseases.}, journal = {Molecules (Basel, Switzerland)}, volume = {30}, number = {3}, pages = {}, pmid = {39942798}, issn = {1420-3049}, mesh = {*Propiophenones/pharmacology/therapeutic use/chemistry ; *Flavonoids/pharmacology/therapeutic use/chemistry ; Humans ; *Neurodegenerative Diseases/drug therapy/prevention & control/metabolism ; Animals ; Antioxidants/pharmacology/therapeutic use/chemistry ; *Neuroprotective Agents/pharmacology/therapeutic use/chemistry ; Parkinson Disease/drug therapy ; Alzheimer Disease/drug therapy/metabolism ; Humulus/chemistry ; }, abstract = {Xanthohumol (XN), a bioactive plant flavonoid, is an antioxidant, and as such, it exhibits numerous beneficial properties, including anti-inflammatory, antimicrobial, and antioxidative effects. The main dietary source of XN is beer, where it is introduced through hops. Although the concentration of XN in beer is low, the large quantities of hop-related post-production waste present an opportunity to extract XN residues for technological or pharmaceutical purposes. The presented study focuses on the role of XN in the prevention of neurodegenerative diseases, analyzing its effect at a molecular level and including its signal transduction and metabolism. The paper brings up XN's mechanism of action, potential effects, and experimental and clinical studies on Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). Additionally, challenges and future research directions on XN, including its bioavailability, safety, and tolerance, have been discussed.}, } @article {pmid39942481, year = {2025}, author = {Kavanaugh, MS and Zawadzki, MJ and Johnson, KT and Boville, MR}, title = {Moments of Care: Perceptions of Young Carers and Day-to-Day Well-Being.}, journal = {Healthcare (Basel, Switzerland)}, volume = {13}, number = {3}, pages = {}, pmid = {39942481}, issn = {2227-9032}, abstract = {Background/Objectives: Over 5 million youth under the age of 19 provide daily, hands-on care to an ill or injured family member across the United States. Yet how these young carers perceive the care they deliver in the moment, and how these perceptions relate to well-being, is unexplored, particularly in complex neurological conditions. This paper presents initial data on young carers for a family member with amyotrophic lateral sclerosis (ALS). Methods: Ecological momentary assessment (EMA) was used to measure perceptions of care in the moments of care and the cognitive and emotional states of the young carers during those moments. Young carers (n = 15) aged 10-19 were followed for seven days, completing assessments three times per day, which provided 260 total measurements. Young carers reported frequently engaging in caregiving (~39% of assessments). Results: The results indicated that it was not simply performing a caregiving task that related to outcomes, but rather how caregiving moments were perceived that mattered. Caregiving moments perceived as more fulfilling resulted in young carers feeling less discontent and more focused, whereas caregiving moments perceived as lacking resources predicted more discontent and distress. Exploratory analyses highlighted the potential for burden for young carers. They reported high levels of worry when they were not around the care recipient, with this worry predicting feeling more discontent and distressed. Conclusions: Young carers are deeply involved in care and perceive care differently across moments, both positive and negative. These initial data can be used to develop targeting support programs in the moment of care, potentially lessening the negative impacts of care.}, } @article {pmid39941101, year = {2025}, author = {Orywal, K and Socha, K and Iwaniuk, P and Kaczyński, P and Farhan, JA and Zoń, W and Łozowicka, B and Perkowski, M and Mroczko, B}, title = {Vitamins in the Prevention and Support Therapy of Neurodegenerative Diseases.}, journal = {International journal of molecular sciences}, volume = {26}, number = {3}, pages = {}, pmid = {39941101}, issn = {1422-0067}, support = {NdS/551580/2022/2022//Polish Ministry of Education and Science/ ; }, mesh = {Humans ; *Neurodegenerative Diseases/prevention & control/drug therapy ; *Vitamins/therapeutic use/pharmacology ; Animals ; Parkinson Disease/prevention & control ; Dietary Supplements ; Neuroprotective Agents/therapeutic use ; Oxidative Stress/drug effects ; }, abstract = {Neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS), which are a consequence of the progressive loss of neuronal function and structure, cause significant cognitive impairment. The incidence of these diseases in the world's population is constantly increasing as a result of an aging population. Although genetic and environmental factors are most often mentioned as the pathogenetic factors of these diseases, increasing evidence points to the important role of proper nutrition in the prevention and support of the treatment of these disorders. A healthy, balanced diet can mitigate the risks associated with the risk factors mentioned above and slow the progression of the disease by reducing oxidative stress and inflammation. Vitamins B, D, E, C, K, and A have been shown to support cognitive functions and protect the nervous system. This review demonstrates the importance of vitamins in preventing and supporting the therapy of neurodegenerative diseases. Information regarding the health-promoting properties of these vitamins must be effectively communicated to consumers seeking to protect their health, particularly in the context of neurodegenerative diseases. Consequently, this review also examines the authorized health claims under EU food law related to these vitamins, assessing their role in promoting awareness of the vitamins' potential benefits for neuroprotection and the management of neurodegenerative diseases.}, } @article {pmid39941012, year = {2025}, author = {Sonkodi, B}, title = {PIEZO2 Proton Affinity and Availability May Also Regulate Mechanical Pain Sensitivity, Drive Central Sensitization and Neurodegeneration.}, journal = {International journal of molecular sciences}, volume = {26}, number = {3}, pages = {}, pmid = {39941012}, issn = {1422-0067}, mesh = {Humans ; *Ion Channels/metabolism/genetics ; Animals ; *Protons ; *Pain/metabolism ; Motor Neurons/metabolism ; *Central Nervous System Sensitization ; *Neurodegenerative Diseases/metabolism ; }, abstract = {The current opinion manuscript posits that not only Piezo2 voltage block, but also proton affinity and availability in relation to Piezo2, a mechanically gated ion channel, may count in the mediation of pain and its sensitivity. Moreover, this paper argues that autonomously acquired Piezo2 channelopathy on somatosensory terminals is likely the initiating peripheral impaired input source that drives the central sensitization of spinal nociceptive neurons on the chronic path as being the autonomous pain generator. In parallel, impaired proprioception and the resultant progressive deficit in neuromuscular junctions of motoneurons might be initiated on the chronic path by the impairment of the proton-based ultrafast proprioceptive feedback to motoneurons due to disconnection through vesicular glutamate transporter 1. The irreversible form of this autonomously acquired Piezo2 ion channel microdamage, in association with genetic predisposition and/or environmental risk factors, is suggested to lead to progressive motoneuron death in addition to loss of pain sensation in amyotrophic lateral sclerosis. Furthermore, the impairment of the proton-based ultrafast long-range oscillatory synchronization to the hippocampus through vesicular glutamate transporter 2 may gain further importance in pain modulation and formation on the chronic path. Overall, this novel, unaccounted Piezo2-initiated protonic extrafast signaling, including both the protonic ultrafast proprioceptive and the rapid nociceptive ones, within the nervous system seems to be essential in order to maintain life. Hence, its microdamage promotes neurodegeneration and accelerates aging, while the complete loss of it is incompatible with life sustainment, as is proposed in amyotrophic lateral sclerosis.}, } @article {pmid39940966, year = {2025}, author = {Jamerlan, AM and Shim, KH and Sharma, N and An, SSA}, title = {Multimer Detection System: A Universal Assay System for Differentiating Protein Oligomers from Monomers.}, journal = {International journal of molecular sciences}, volume = {26}, number = {3}, pages = {}, pmid = {39940966}, issn = {1422-0067}, support = {RS-2023-00251396//National Research Foundation of Korea/ ; 2021R1A6A1A03038996//National Research Foundation of Korea/ ; }, mesh = {Humans ; alpha-Synuclein/metabolism ; *Protein Multimerization ; *Neurodegenerative Diseases/metabolism ; Protein Aggregates ; tau Proteins/metabolism ; Amyloid beta-Peptides/metabolism ; *Protein Aggregation, Pathological/metabolism ; DNA-Binding Proteins/metabolism ; }, abstract = {Depositions of protein aggregates are typical pathological hallmarks of various neurodegenerative diseases (NDs). For example, amyloid-beta (Aβ) and tau aggregates are present in the brain and plasma of patients with Alzheimer's disease (AD); α-synuclein in Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA); mutant huntingtin protein (Htt) in Huntington's disease (HD); and DNA-binding protein 43 kD (TDP-43) in amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and limbic-predominant age-related TDP-43 encephalopathy (LATE). The same misfolded proteins can be present in multiple diseases in the form of mixed proteinopathies. Since there is no cure for all these diseases, understanding the mechanisms of protein aggregation becomes imperative in modern medicine, especially for developing diagnostics and therapeutics. A Multimer Detection System (MDS) was designed to distinguish and quantify the multimeric/oligomeric forms from the monomeric form of aggregated proteins. As the unique epitope of the monomer is already occupied by capturing or detecting antibodies, the aggregated proteins with multiple epitopes would be accessible to both capturing and detecting antibodies simultaneously, and signals will be generated from the oligomers rather than the monomers. Hence, MDS could present a simple solution for measuring various conformations of aggregated proteins with high sensitivity and specificity, which may help to explore diagnostic and treatment strategies for developing anti-aggregation therapeutics.}, } @article {pmid39940644, year = {2025}, author = {Lee, AJB and Bi, S and Ridgeway, E and Al-Hussaini, I and Deshpande, S and Krueger, A and Khatri, A and Tsui, D and Deng, J and Mitchell, CS}, title = {Restoring Homeostasis: Treating Amyotrophic Lateral Sclerosis by Resolving Dynamic Regulatory Instability.}, journal = {International journal of molecular sciences}, volume = {26}, number = {3}, pages = {}, pmid = {39940644}, issn = {1422-0067}, support = {U19 AG065169/AG/NIA NIH HHS/United States ; 1944247//National Science Foundation/ ; 253558//Chan Zuckerberg Initiative/ ; R35 GM152245/GM/NIGMS NIH HHS/United States ; T32 EB025816/EB/NIBIB NIH HHS/United States ; R35GM152245/NH/NIH HHS/United States ; K01 NS069616/NS/NINDS NIH HHS/United States ; }, mesh = {*Amyotrophic Lateral Sclerosis/metabolism/therapy/genetics/pathology/drug therapy/physiopathology ; Animals ; *Homeostasis ; Mice ; Mice, Transgenic ; Disease Models, Animal ; Superoxide Dismutase-1/genetics/metabolism ; Humans ; Disease Progression ; Computer Simulation ; }, abstract = {Amyotrophic lateral sclerosis (ALS) has an interactive, multifactorial etiology that makes treatment success elusive. This study evaluates how regulatory dynamics impact disease progression and treatment. Computational models of wild-type (WT) and transgenic SOD1-G93A mouse physiology dynamics were built using the first-principles-based first-order feedback framework of dynamic meta-analysis with parameter optimization. Two in silico models were developed: a WT mouse model to simulate normal homeostasis and a SOD1-G93A ALS model to simulate ALS pathology dynamics and their response to in silico treatments. The model simulates functional molecular mechanisms for apoptosis, metal chelation, energetics, excitotoxicity, inflammation, oxidative stress, and proteomics using curated data from published SOD1-G93A mouse experiments. Temporal disease progression measures (rotarod, grip strength, body weight) were used for validation. Results illustrate that untreated SOD1-G93A ALS dynamics cannot maintain homeostasis due to a mathematical oscillating instability as determined by eigenvalue analysis. The onset and magnitude of homeostatic instability corresponded to disease onset and progression. Oscillations were associated with high feedback gain due to hypervigilant regulation. Multiple combination treatments stabilized the SOD1-G93A ALS mouse dynamics to near-normal WT homeostasis. However, treatment timing and effect size were critical to stabilization corresponding to therapeutic success. The dynamics-based approach redefines therapeutic strategies by emphasizing the restoration of homeostasis through precisely timed and stabilizing combination therapies, presenting a promising framework for application to other multifactorial neurodegenerative diseases.}, } @article {pmid39939579, year = {2025}, author = {Zhou, T and Solis, NV and Marshall, M and Yao, Q and Pearlman, E and Filler, SG and Liu, H}, title = {Fungal Als proteins hijack host death effector domains to promote inflammasome signaling.}, journal = {Nature communications}, volume = {16}, number = {1}, pages = {1562}, pmid = {39939579}, issn = {2041-1723}, support = {R01 EY036478/EY/NEI NIH HHS/United States ; R01 GM117111/GM/NIGMS NIH HHS/United States ; R01EY036478//U.S. Department of Health & Human Services | NIH | National Eye Institute (NEI)/ ; R01GM117111//U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)/ ; }, mesh = {Humans ; *Inflammasomes/metabolism/immunology ; Animals ; Mice ; Caspase 8/metabolism ; Signal Transduction ; Interleukin-1beta/metabolism ; Jurkat Cells ; *Fungal Proteins/metabolism/genetics/immunology ; Fas-Associated Death Domain Protein/metabolism ; CARD Signaling Adaptor Proteins/metabolism ; *Candida albicans/metabolism/immunology ; Macrophages/metabolism/immunology ; Mice, Inbred C57BL ; Apoptosis ; Colitis ; }, abstract = {High-damaging Candida albicans strains tend to form hyphae and exacerbate intestinal inflammation in ulcerative colitis patients through IL-1β-dependent mechanisms. Fungal agglutinin-like sequence (Als) proteins worsen DSS-induced colitis in mouse models. FADD and caspase-8 are important regulators of gut homeostasis and inflammation. However, whether they link directly to fungal proteins is not fully understood. Here, we report that Als proteins induce IL-1β release in immune cells. We show that hyphal Als3 is internalized in macrophages and interacts with caspase-8 and the inflammasome adaptor apoptosis-associated speck-like protein containing a CARD (ASC). Caspase-8 is essential for Als3-mediated ASC oligomerization and IL-1β processing. In non-immune cells, Als3 is associated with cell death core components FADD and caspase-8. N-terminal Als3 (N-Als3) expressed in Jurkat cells partially inhibits apoptosis. Mechanistically, N-Als3 promotes oligomerization of FADD and caspase-8 through their death effector domains (DEDs). N-Als3 variants with a mutation in the peptide-binding cavity or amyloid-forming region are impaired in DED oligomerization. Together, these results demonstrate that DEDs are intracellular sensors of Als3. This study identifies additional potential targets to control hypha-induced inflammation.}, } @article {pmid39938954, year = {2025}, author = {Flügel, V and Hering, T and Dadaczynski, K}, title = {Development and validation of a questionnaire on parental health literacy in the context of promoting healthy lifestyles during childhood: a study protocol.}, journal = {BMJ open}, volume = {15}, number = {2}, pages = {e088037}, pmid = {39938954}, issn = {2044-6055}, mesh = {Humans ; *Health Literacy ; *Parents/education ; Surveys and Questionnaires/standards ; Child ; Child, Preschool ; *Health Promotion ; *Healthy Lifestyle ; Reproducibility of Results ; Female ; Research Design ; Male ; }, abstract = {INTRODUCTION: Becoming a parent presents profound changes and numerous challenges, notably the necessity for reliable information regarding their child's health. Given the overabundance of information available today, it is important for parents to acquire the skills necessary to find, understand, evaluate and apply health information. Research demonstrates that this ability, known as parental health literacy (PHL), is crucial for developing and maintaining a healthy lifestyle during childhood. However, there is currently no reliable instrument for measuring PHL in the field of prevention and health promotion. This paper presents the development and validation of a new questionnaire designed to assess parents' ability to process health-related information to support the healthy development of their children aged 3-6 years.

METHODS AND ANALYSIS: The development of the item pool is based on Sørensen et al's conceptualisation of general health literacy (finding, understanding, evaluating and applying health information). Empirical findings suggest that communication with healthcare providers and the social network represents another important skill area for parents and is therefore included as an additional subscale. The questionnaire will be developed in four stages, including a literature search and analysis, expert consultations via Delphi study, cognitive interviews with parents and a validation study. The validation study uses exploratory (EFA) and confirmatory factor analysis (CFA) for construct validity, first identifying test dimensions through EFA, then confirming these dimensions with CFA to ensure the factor structure aligns with theoretical expectations. This methodology, alongside reliability and correlational analyses, seeks to assess the questionnaire's validity and reliability, expecting strong correlations with existing related constructs.

ETHICS AND DISSEMINATION: Ethical approval was obtained from the Ethics Committee of Fulda University of Applied Sciences. All participants receive a consent form together with the study information, in which they give their written consent to the storage, processing and linking of all data collected. The results of the study will be presented at national and international conferences and published in specialist journals.

TRIAL REGISTRATION NUMBER: DRKS00033482.}, } @article {pmid39938752, year = {2025}, author = {Zhu, Y and Tian, M and Lu, S and Qin, Y and Zhao, T and Shi, H and Li, Z and Qin, D}, title = {The antioxidant role of aromatic plant extracts in managing neurodegenerative diseases: A comprehensive review.}, journal = {Brain research bulletin}, volume = {222}, number = {}, pages = {111253}, doi = {10.1016/j.brainresbull.2025.111253}, pmid = {39938752}, issn = {1873-2747}, mesh = {Humans ; *Neurodegenerative Diseases/drug therapy/metabolism ; *Antioxidants/pharmacology/therapeutic use ; *Plant Extracts/pharmacology/therapeutic use ; Oxidative Stress/drug effects ; Animals ; Polyphenols/pharmacology/therapeutic use ; }, abstract = {Neurodegenerative diseases (NDDs) are a class of cognitive and motor disorders including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), Amyotrophic Lateral Sclerosis (ALS), and others. They are caused by lesions in cells and tissues of the central nervous system, resulting in corresponding dysfunctions and consequent decline in cognitive and motor functions. Neural tissues are extremely vulnerable to oxidative stress, which plays critical biological roles in NDDs. Aromatic compounds are found extensively in natural plants and have substantial effects of anti-oxidative stress damage, which not only have a wide range of research applications in cosmetics, foods, etc., but are also frequently utilized in the treatment of various central nervous system diseases. This review summarizes the relevant oxidative stress mechanisms in NDDs (AD, PD, HD, and ALS) and reviews aromatic compounds such as polyphenols, terpenoids, and flavonoids that can be used in the management of neurodegenerative diseases, as well as their specific mechanisms of antioxidant action. This review will serve as a reference for future experimental studies on neurodegenerative illnesses while also offering fresh insights into clinical therapy.}, } @article {pmid39937422, year = {2025}, author = {Grassano, M and Chiò, A}, title = {microRNA in ALS: finally ready for prime time?.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {46}, number = {4}, pages = {1463-1464}, pmid = {39937422}, issn = {1590-3478}, } @article {pmid39936986, year = {2025}, author = {Ramírez, OA and Hellwig, A and Zhang, Z and Bading, H}, title = {Pharmacological Targeting of the NMDAR/TRPM4 Death Signaling Complex with a TwinF Interface Inhibitor Prevents Excitotoxicity-Associated Dendritic Blebbing and Organelle Damage.}, journal = {Cells}, volume = {14}, number = {3}, pages = {}, pmid = {39936986}, issn = {2073-4409}, mesh = {*TRPM Cation Channels/metabolism ; *Receptors, N-Methyl-D-Aspartate/metabolism ; *Dendrites/drug effects/metabolism/pathology/ultrastructure ; Animals ; Mitochondria/metabolism/drug effects ; Endoplasmic Reticulum/metabolism/drug effects ; Humans ; Signal Transduction/drug effects ; *Organelles/drug effects/metabolism/pathology ; Mice ; Glutamic Acid ; Calcium/metabolism ; Neurons/metabolism/drug effects ; }, abstract = {Focal swellings of dendrites ("dendritic blebbing") together with structural damage of mitochondria and the endoplasmic reticulum (ER) are morphological hallmarks of glutamate neurotoxicity, also known as excitotoxicity. These pathological alterations are generally thought to be caused by the so-called "overactivation" of N-methyl-D-aspartate receptors (NMDARs). Here, we demonstrate that the activation of extrasynaptic NMDARs, specifically when forming a protein-protein complex with TRPM4, drives these pathological traits. In contrast, strong activation of synaptic NMDARs fails to induce cell damage despite evoking plateau-type calcium signals that are comparable to those generated by activation of the NMDAR/TRPM4 complex, indicating that high intracellular calcium levels per se are not toxic to neurons. Using confocal laser scanning microscopy and transmission electron microscopy, we show that disrupting the NMDAR/TRPM4 complex using the recently discovered small-molecule TwinF interface inhibitor FP802 inhibits the NMDA-induced neurotoxicity-associated dendritic blebbing and structural damage to mitochondria and the ER. It also prevents, at least in part, the disruption of ER-mitochondria contact sites. These findings establish the NMDAR/TRPM4 complex as the trigger for the structural damage of dendrites and intracellular organelles associated with excitotoxicity. They also suggest that activation of the NMDAR/TRPM4 complex, in addition to inducing high-amplitude, plateau-type calcium signals, generates a second signal required for glutamate neurotoxicity ("two-hit hypothesis"). As structural damage to organelles, particularly mitochondria, is a common feature of many human neurodegenerative diseases, including Alzheimer's disease and amyotrophic lateral sclerosis (ALS), TwinF interface inhibitors have the potential to provide neuroprotection across a broad spectrum of these diseases.}, } @article {pmid39936815, year = {2025}, author = {Mendes, RA and Lima, ILB and Dourado Júnior, MET and Gonçalves, MJ}, title = {Is there a decline in speech and swallowing in Amyotrophic Lateral Sclerosis over ten years?.}, journal = {CoDAS}, volume = {37}, number = {2}, pages = {e20240159}, pmid = {39936815}, issn = {2317-1782}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology/complications ; Male ; *Deglutition Disorders/etiology/physiopathology ; Female ; Retrospective Studies ; Middle Aged ; Longitudinal Studies ; Aged ; Disease Progression ; Dysarthria/etiology/physiopathology ; *Speech Disorders/etiology/physiopathology ; Adult ; Deglutition/physiology ; Time Factors ; Aged, 80 and over ; }, abstract = {PURPOSE: To analyze the evolution of speech and swallowing decline in patients with amyotrophic lateral sclerosis (ALS) over a ten-year period.

METHODS: A retrospective and longitudinal cohort study. Data were collected using the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) from 101 medical records of ALS patients treated at the multidisciplinary neuromuscular diseases clinic of a University Hospital over a ten-year period. The data were statistically analyzed, adopting a significance level of p<0.05.

RESULTS: The analysis of the studied functions indicated that speech, swallowing, and salivation are altered over ten years in ALS. There are differences in patterns between the variables sex and disease type concerning symptoms related to dysarthria and dysphagia in these individuals, which may indicate the rate of progression over a given time interval.

CONCLUSION: There is a decline in speech and swallowing over ten years in ALS. The bulbar type leads to a faster decline in the studied functions than the spinal type.}, } @article {pmid39936380, year = {2025}, author = {Lero, CM and Yang, A and Everett, E and Pitzer, KA and McCoy Gross, K and Washington, KT}, title = {Associations Between End-Stage ALS Care and Specialty Palliative Care: A Hypothesis-Generating Study.}, journal = {Muscle & nerve}, volume = {71}, number = {4}, pages = {632-638}, pmid = {39936380}, issn = {1097-4598}, support = {T32 MH019960/MH/NIMH NIH HHS/United States ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy ; Female ; Male ; *Palliative Care/methods ; Middle Aged ; Aged ; *Terminal Care ; Electronic Health Records ; Aged, 80 and over ; }, abstract = {INTRODUCTION/AIMS: Amyotrophic lateral sclerosis (ALS) care is typically delivered via a multidisciplinary approach that may include specialty palliative care (SPC). Opportunities for SPC to enhance ALS care have been identified; however, investigation of these proposed benefits is scant. In this exploratory study, investigators examined associations between receipt of SPC and variables particularly relevant to end-stage ALS.

METHODS: Researchers reviewed electronic health records for all patients with ALS who received standard ALS care from one Midwestern US academic medical center and died between January 1, 2020, and June 30, 2022 (N = 156). Receipt of SPC, duration of illness, hospice enrollment and length of service, report of a healthcare proxy, documentation of a healthcare proxy, participation in goals of care conversations, and location of death were examined.

RESULTS: Patients who received SPC (59%), had lower mean forced vital capacity (FVC) (p < 0.05), and more often used respiratory support (p < 0.001), participated in goals of care conversations (p < 0.001), reported a healthcare proxy (p < 0.01), and enrolled in hospice (p < 0.001) than patients who received standard care alone. No differences between groups were found in duration of illness (mean = 51.7 months), use of assistive feeding, Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) scores (mean = 32.1), documentation of a healthcare proxy, length of hospice stay (mean = 47.3 days), or location of death.

DISCUSSION: Clinical characteristics and end-of-life outcome differences between groups support further investigation of the proposed benefits of SPC regarding hospice enrollment, report of healthcare proxies, and documented goals of care conversations.}, } @article {pmid39936266, year = {2025}, author = {Denton, TT and Carter, GT and Goddard, M and Weiss, J and Weeks, DL and Weydt, P and Russo, EB and Weiss, MD}, title = {Amyotrophic Lateral Sclerosis, the Endocannabinoid System, and Exogenous Cannabinoids: Current State and Clinical Implications.}, journal = {Muscle & nerve}, volume = {72}, number = {1}, pages = {7-14}, doi = {10.1002/mus.28359}, pmid = {39936266}, issn = {1097-4598}, mesh = {*Amyotrophic Lateral Sclerosis/drug therapy/metabolism ; Humans ; Animals ; *Cannabinoids/therapeutic use/pharmacology ; *Endocannabinoids/metabolism/therapeutic use ; Mice ; }, abstract = {A unifying mechanistic cause for amyotrophic lateral sclerosis (ALS) remains uncertain. Multiple pathophysiological processes appear to occur simultaneously. Cannabinoids, including delta-9-tetrahydrocannabinol (THC), cannabidiol (CBD), cannabigerol (CBG), and others found in cannabis, and cannabis extracts (CEs), appear to have activity in these pathogenic pathways, which have led to increasing interest in cannabinoids as therapeutic agents for ALS. The use of cannabinoids as a treatment strategy is substantiated by preclinical evidence suggesting a role for the endocannabinoid system (ECS) in ALS and other neurodegenerative disorders. Preclinical data indicate that cannabis and CEs have powerful antioxidative, anti-inflammatory, and neuroprotective effects in the SOD1 [G93A] mouse model of ALS. The use of CEs in SOD1 [G93A] murine models has been shown to prolong neuronal cell survival, which leads to delayed onset of the disease state, and slows progression of the disease. Although research in humans remains limited, a few studies suggest that cannabis and CBD, in humans, provide benefits for both motor symptoms, including rigidity, cramps, and fasciculations, and non-motor symptoms including sleep quality, pain, emotional state, quality of life, and depression. There remains a need for further, well-designed clinical trials to validate further the use of an individual cannabinoid, or a combination of cannabinoids, as a disease-modifying therapy for ALS.}, } @article {pmid39936211, year = {2025}, author = {Naveed, A and Usmani, WA and Vandara, MP and Karmani, VK}, title = {Tofersen for Amyotrophic Lateral Sclerosis: A Step Forward or Another False Hope?.}, journal = {Journal of the College of Physicians and Surgeons--Pakistan : JCPSP}, volume = {35}, number = {2}, pages = {259-260}, doi = {10.29271/jcpsp.2025.02.259}, pmid = {39936211}, issn = {1681-7168}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy ; Treatment Outcome ; }, abstract = {Null.}, } @article {pmid39936179, year = {2025}, author = {Morrison, AH and Jimenez, JV and Hsu, JY and Elman, L and Choi, PJ and Ackrivo, J}, title = {Identifying Daytime Hypercapnia Using Transcutaneous Carbon Dioxide Monitoring in Patients With Amyotrophic Lateral Sclerosis.}, journal = {Muscle & nerve}, volume = {71}, number = {4}, pages = {611-619}, pmid = {39936179}, issn = {1097-4598}, support = {K23 HL151879/HL/NHLBI NIH HHS/United States ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/complications/physiopathology ; *Hypercapnia/diagnosis/etiology/epidemiology ; Male ; Female ; Middle Aged ; Retrospective Studies ; Aged ; *Carbon Dioxide/blood ; *Blood Gas Monitoring, Transcutaneous/methods ; Respiratory Function Tests ; Vital Capacity ; Adult ; }, abstract = {INTRODUCTION/AIMS: Respiratory failure from hypoventilation is the most common cause of death in amyotrophic lateral sclerosis (ALS). However, ALS care rarely assesses hypercapnia, a physiologic measure of hypoventilation. We investigated the prevalence and clinical significance of daytime hypercapnia measured by transcutaneous carbon dioxide (tcCO2) monitoring in patients with ALS.

METHODS: This retrospective study included patients seen at two ALS clinics in the United States between 2012 and 2024 who had tcCO2 measured concurrently with pulmonary function tests (PFTs), which included forced vital capacity (FVC) and, at one site, maximum inspiratory pressure (MIP). We assessed the prevalence of hypercapnia (tcCO2 > 45 mmHg), the sensitivity and specificity of patient symptoms and PFTs for hypercapnia, and the relationship between hypercapnia and survival.

RESULTS: Daytime hypercapnia was present in 33/328 (10%) patients at baseline. Hypercapnia was associated with an increased rate of death (aHR 2.1, 95% CI 1.4-3.3). Orthopnea or dyspnea was 70% sensitive for hypercapnia (95% CI 51%-84%). Absolute value of MIP (|MIP|) < 60 cmH2O was 95% sensitive (95% CI 74%-100%) and 22% specific (95% CI 16%-30%), FVC < 50% predicted was 33% sensitive (95% CI 18%-52%) and 82% specific (95% CI 78%-87%), and FVC < 80% predicted was 85% sensitive (95% CI 68%-95%) and 31% specific (95% CI 26%-36%) for hypercapnia.

DISCUSSION: TcCO2 monitoring identified strengths and weaknesses of PFTs in identifying hypercapnia in ALS. We found high sensitivity of |MIP| < 60 cmH2O and FVC < 80% predicted and high specificity of FVC < 50% predicted. Prospective studies should investigate the optimal clinical role for tcCO2.}, } @article {pmid39935503, year = {2025}, author = {Tsuruta, M and Shil, S and Taniguchi, S and Kawauchi, K and Miyoshi, D}, title = {The role of cytosine methylation in regulating the topology and liquid-liquid phase separation of DNA G-quadruplexes.}, journal = {Chemical science}, volume = {16}, number = {10}, pages = {4213-4225}, pmid = {39935503}, issn = {2041-6520}, abstract = {Aberrant expansion of GGGGCC DNA repeats that form G-quadruplexes (G4) is the main cause of amyotrophic lateral sclerosis (ALS). Expanded GGGGCC repeats induce liquid-liquid phase separation (LLPS) through their interaction with cellular proteins. Furthermore, GGGGCC expansion induces cytosine methylation (mC). Previous studies have shown that even slight chemical modifications of RNAs and proteins can drastically affect their LLPS ability, yet the relationship between LLPS and epigenetic DNA modifications like mC remains unexplored. As a model system, we investigated the effects of mC on LLPS induced by GGGGCC repeat DNAs and show for the first time that mC suppresses LLPS by altering the topology of G4 from being parallel to antiparallel.}, } @article {pmid39933444, year = {2025}, author = {Rob, M and Yousef, M and Lakshmanan, AP and Mahboob, A and Terranegra, A and Chaari, A}, title = {Microbial signatures and therapeutic strategies in neurodegenerative diseases.}, journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie}, volume = {184}, number = {}, pages = {117905}, doi = {10.1016/j.biopha.2025.117905}, pmid = {39933444}, issn = {1950-6007}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Neurodegenerative Diseases/microbiology/therapy/metabolism ; Animals ; Dysbiosis ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; Metabolome ; }, abstract = {Neurodegenerative diseases (NDs), including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS), arise from complex interactions between genetic factors, environmental exposures, and aging. Additionally, gut dysbiosis has been linked to systemic inflammation and neurodegeneration. Advances in microbiome and metabolome profiling techniques have provided deeper insights into how alterations in gut microbiota and dietary patterns affect metabolic pathways and contribute to the progression of NDs. This review explores the profiles of gut microbiome and metabolome derived biomarkers and their roles in NDs. Across phyla, families, and genera, we identified 55 microbial alterations in PD, 24 in AD, 4 in ALS, and 17 in MS. Some notable results include an increase in Akkermansia in PD, AD, and MS and a decrease in short-chain fatty acids (SCFAs) in PD and AD. We examined the effects of probiotics, prebiotics, fecal microbiota transplants (FMT), sleep, exercise, and diet on the microbiota, all of which contributed to delayed onset and alleviation of symptoms. Further, artificial intelligence (AI) and machine learning (ML) algorithms applied to omics data have been crucial in identifying novel therapeutic targets, diagnosing and predicting prognosis, and enabling personalized medicine using microbiota-modulating therapies in NDs patients.}, } @article {pmid39933412, year = {2025}, author = {Noli, B and Borghero, G and Mascia, MM and Hkir, M and Puligheddu, M and Cocco, C}, title = {NERP-1 modifications in amyotrophic lateral sclerosis.}, journal = {Tissue & cell}, volume = {93}, number = {}, pages = {102780}, doi = {10.1016/j.tice.2025.102780}, pmid = {39933412}, issn = {1532-3072}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/blood/pathology/metabolism ; Female ; Male ; Middle Aged ; Motor Neurons/metabolism/pathology ; Aged ; Oxidative Stress ; Adult ; *Neuropeptides/blood ; Cell Line ; Nerve Growth Factors ; }, abstract = {VGF peptides, such as NERPs (neuroendocrine regulatory peptides 1 and 2), are derived from amino acids 282-306 and 313-350, respectively, of the human proVGF, which is produced in spinal cord motor neurons. Although certain VGF-derived peptides are changed in ALS, less is known about NERPs. Possible modulations of NERPs and additional VGF peptides (NAPP and TPGH) were investigated using specific antibodies through competitive ELISA in the plasma of ALS patients (at both the initial and advanced phases; n = 46 each vs. 46 controls). As additional controls, naïve PD patients were also enrolled (n = 19 vs. 18 controls) while the potential VGF peptide role in oxidative stress was investigated using a motoneuron-like cell line (NSC34) stressed with sodium arsenate (SA). Western blot (WB) and sephadex chromatography (SC) were used to identify the molecular weight (MW) forms recognized by the VGF antibodies. Exclusively NERP-1 immunoreactivity was changed (elevated) in all plasma samples of ALS patients (compared to controls). Therefore, the NERP-1 antibody was the sole antibody used in ELISA with PD samples and NSC-34 cells. No alterations were seen in PD samples (vs. controls) while NERP-1 immunoreactivity decreased within SA-treated cells but increased in their culture medium. The viability test performed by adding NERP-1 to the stressed cells showed no protective effect. Using WB and SC, we revealed NERP-1 antibody reactivity against various MW forms, including those compatible with the NERP-1 peptide and/or proVGF. NERP-1 is suggested as a possible ALS blood biomarker.}, } @article {pmid39933343, year = {2025}, author = {Hatamli, K and Eritja, R and Giménez, E and Benavente, F and Gargallo, R}, title = {Resolution of complex mixtures of duplex and antiparallel triplex DNA structures by capillary electrophoresis and multivariate analysis.}, journal = {Talanta}, volume = {288}, number = {}, pages = {127616}, doi = {10.1016/j.talanta.2025.127616}, pmid = {39933343}, issn = {1873-3573}, mesh = {Electrophoresis, Capillary/methods ; *DNA/chemistry/analysis ; Multivariate Analysis ; Nucleic Acid Conformation ; Spectrophotometry, Ultraviolet ; Least-Squares Analysis ; }, abstract = {Triplex DNA structures, which are formed by the addition of an extra strand to a target B-DNA duplex, have attracted increasing interest due to their analytical and therapeutic applications. These structures are classified into parallel and antiparallel, depending on the orientation of the Triplex-Forming Oligonucleotide (TFO) relative to the B-DNA duplex. Whereas the formation of parallel triplexes is easily detected by monitoring spectral changes in the UV region, the formation of antiparallel triplexes produces small or even no spectral variations, which makes their detection difficult and uncertain. In this study, we propose the use of capillary electrophoresis with ultraviolet absorption spectrophotometric (CE-UV) detection combined with the multivariate curve resolution-alternating least squares (MCR-ALS) chemometric method to analyse mixtures of DNA sequences capable of forming mixtures of B-DNA duplex and triplex antiparallel structures. Rapid and reproducible CE-UV analysis in hydroxypropylcellulose (HPC)-coated capillaries are done in a pH 7.4 buffer containing Mg(II) for the stabilization of the intermolecular species. Spectra measured from 220 to 300 nm along the CE-UV analysis of individual DNA strands and of their mixtures at different ratios are merged into an augmented data matrix. This is later analyzed with MCR-ALS to deconvolute characteristic pure spectra and electropherograms for each one of the CE-UV analysis considered. This procedure has allowed the resolution and detection of DNA species present in mixtures of DNA strands capable of forming duplexes, as well as antiparallel triplex structures.}, } @article {pmid39933303, year = {2025}, author = {Zeng, JY and Huang, HW and Zhuang, SP and Wu, Y and Chen, S and Zou, ZY and Chen, HJ}, title = {Soma and neurite density imaging detects brain microstructural impairments in amyotrophic lateral sclerosis.}, journal = {European journal of radiology}, volume = {184}, number = {}, pages = {111981}, doi = {10.1016/j.ejrad.2025.111981}, pmid = {39933303}, issn = {1872-7727}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/pathology/diagnostic imaging ; Male ; Female ; Middle Aged ; *Neurites/pathology ; *Diffusion Tensor Imaging/methods ; *Brain/pathology ; Aged ; Adult ; Sensitivity and Specificity ; *Diffusion Magnetic Resonance Imaging/methods ; Reproducibility of Results ; *Image Interpretation, Computer-Assisted/methods ; }, abstract = {OBJECTIVE: To investigate whole-brain microstructural changes in amyotrophic lateral sclerosis (ALS) using soma and neurite density imaging (SANDI), a novel multicompartment model of diffusion-weighted imaging that estimates apparent soma and neurite density.

METHODS: This study consists of 41 healthy controls and 43 patients with ALS, whose diffusion-weighted data were acquired. The SANDI-derived (including signal fractions of soma (fsoma), neurite (fneurite), and extra-cellular space (fextra)) and diffusion tensor imaging (DTI)-derived metrics were obtained. Voxel-based analyses were performed to evaluate intergroup differences and the correlation of SANDI and DTI metrics with clinical parameters.

RESULTS: In ALS patients, fneurite reduction involved both gray matter (primarily the bilateral precentral gyri, supplementary motor area, medial frontal gyrus, anterior cingulate cortex, inferior frontal gyrus, orbital gyrus, paracentral lobule, postcentral gyrus, middle cingulate cortex, hippocampus and parahippocampal gyrus, and insula, and left anterior parts of the temporal lobe) and white matter (primarily the bilateral corticospinal tract, body of corpus callosum, and brainstem) (P <0.05 after false discovery rate correction). The fextra increment showed a similar spatial distribution in ALS patients. Interestingly, the decreased fsoma in ALS primarily located in gray matter; while, the increased fsoma primarily involved white matter. The spatial distribution of fneurite/fextra/fsoma changes was larger than that detected by conventional DTI metrics, and the fneurite/fextra/fsoma were correlated with disease severity.

CONCLUSIONS: SANDI may serve as a clinically relevant model, superior to conventional DTI, for characterizing microstructural impairments such as neurite degeneration and soma alteration in ALS.}, } @article {pmid39933302, year = {2025}, author = {Li, H and Qiao, Z and Xiao, X and Cao, X and Li, Z and Liu, M and Jiao, Q and Chen, X and Du, X and Jiang, H}, title = {G protein-coupled receptors: A golden key to the treasure-trove of neurodegenerative diseases.}, journal = {Clinical nutrition (Edinburgh, Scotland)}, volume = {46}, number = {}, pages = {155-168}, doi = {10.1016/j.clnu.2025.01.032}, pmid = {39933302}, issn = {1532-1983}, mesh = {Humans ; *Neurodegenerative Diseases/drug therapy/metabolism ; *Receptors, G-Protein-Coupled/metabolism ; Signal Transduction ; Animals ; }, abstract = {G protein-coupled receptors (GPCRs) are a class of transmembrane proteins that distribute in various organs extensively. They can regulate physiological functions such as perception, neurotransmission and endocrinology through the synergies of signaling pathways. At present, Food and Drug Administration (FDA) have approved more than 500 drugs targeting GPCRs to treat a variety of conditions, including neurological diseases, gastrointestinal diseases and tumors. Conformational diversity and dynamic changes make GPCRs a star target for the treatment of neurodegenerative diseases. Moreover, GPCRs can also open biased signaling pathways for G protein and β-arrestin, which has unique functional selectivity and the possibility of overcoming side effects. Some studies believe that biased drugs will be the mainstream direction of drug innovation in the future. To disclose the essential role and research process of GPCRs in neurodegenerative diseases, we firstly reviewed several pivotal GPCRs and their mediated signaling pathways in Alzheimer's disease (AD), Parkinson's disease (PD) and Amyotrophic lateral sclerosis (ALS). Then we focused on the biased signaling pathway of GPCRs in these diseases. Finally, we updated the GPCR drugs under research for the treatment of neurodegenerative diseases in the clinical trials or approval. This review could provide valuable targets for precision therapy to cope with the dysfunction of neurodegenerative diseases in the future.}, } @article {pmid39932579, year = {2025}, author = {Ando, M and Higuchi, Y and Yuan, JH and Yoshimura, A and Yano, C and Hobara, T and Kojima, F and Hiramatsu, Y and Nozuma, S and Nakamura, T and Sakiyama, Y and Hashiguchi, A and Okamoto, Y and Matsushige, T and Mitsui, J and Tsuji, S and Takashima, H}, title = {SOD1-related inherited peripheral neuropathies in a Japanese cohort: genetic variants and clinical insights.}, journal = {Journal of neurology}, volume = {272}, number = {3}, pages = {191}, pmid = {39932579}, issn = {1432-1459}, support = {2016100002B//Ministry of Health, Labour and Welfare/ ; 201442014A//Agency for Medical Research and Development/ ; 201442071A//Agency for Medical Research and Development/ ; 18H02742//JSPS KAKENHI/ ; 20K16604//JSPS KAKENHI/ ; 21K15702//JSPS KAKENHI/ ; 21H02842//JSPS KAKENHI/ ; 22K15713//JSPS KAKENHI/ ; 22K07495//JSPS KAKENHI/ ; 22K07519//JSPS KAKENHI/ ; 23K06931//JSPS KAKENHI/ ; }, mesh = {Humans ; Male ; Female ; *Superoxide Dismutase-1/genetics ; Middle Aged ; Adult ; Japan ; *Peripheral Nervous System Diseases/genetics/physiopathology/diagnosis ; Aged ; Cohort Studies ; Young Adult ; East Asian People ; }, abstract = {BACKGROUND: Inherited peripheral neuropathies (IPNs) encompass a wide range of disorders affecting the peripheral nervous system, often with complex genetic causes and frequent underdiagnosis. The variants in the superoxide dismutase 1 (SOD1) gene, primarily linked to amyotrophic lateral sclerosis (ALS), have also been associated with peripheral neuropathy. The recent approval of Tofersen, targeting SOD1-related ALS, highlights the importance of precise genetic diagnosis. This study explores the clinical and genetic profiles of SOD1-related IPNs (SOD1-IPN) in a nationwide Japanese IPN cohort.

METHODS: Clinical and genetic data were assessed from 1483 Japanese patients with IPN, with a focus on those harboring SOD1 pathogenic variants. The clinical evaluations included age of onset, gender, muscle weakness patterns, sensory disturbances, reflex responses, and electrophysiological findings.

RESULTS: Seventeen patients with SOD1 pathogenic variants were identified, reinforcing SOD1's role in IPN. The average onset age was 47, with a slight male predominance. Distal muscle weakness was noted in 9 of 13 patients, and asymmetric muscle weakness and atrophy in 10 of 14 cases. Mild sensory disturbances were observed in eight patients, with some showing hyperreflexia and abnormal reflexes. Electrophysiology predominantly indicated a length-dependent, motor-dominant axonal neuropathy.

CONCLUSION: This study reveals the clinical variability and likely underdiagnosis of SOD1-IPN, supporting the integration of SOD1 screening in IPN genetic testing, especially for patients with asymmetric, length-dependent axonal neuropathy evident in clinical and electrophysiological assessments.}, } @article {pmid39932195, year = {2025}, author = {Ruggieri, V and Scaricamazza, S and Bracaglia, A and D'Ercole, C and Parisi, C and D'Angelo, P and Proietti, D and Cappelletti, C and Macone, A and Lozanoska-Ochser, B and Bouchè, M and Latella, L and Valle, C and Ferri, A and Giordani, L and Madaro, L}, title = {Polyamine metabolism dysregulation contributes to muscle fiber vulnerability in ALS.}, journal = {Cell reports}, volume = {44}, number = {1}, pages = {115123}, doi = {10.1016/j.celrep.2024.115123}, pmid = {39932195}, issn = {2211-1247}, mesh = {Animals ; *Amyotrophic Lateral Sclerosis/metabolism/pathology/genetics ; *Polyamines/metabolism ; *Muscle Fibers, Skeletal/metabolism/pathology ; Mice ; Superoxide Dismutase-1/metabolism/genetics ; Mice, Transgenic ; Disease Models, Animal ; Humans ; Motor Neurons/metabolism/pathology ; Muscle, Skeletal/metabolism/pathology ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease causing progressive paralysis due to motor neuron degeneration with no curative therapy despite extensive biomedical research. One of the primary targets of ALS is skeletal muscle, which undergoes profound functional changes as the disease progresses. To better understand how altered innervation interferes with muscle homeostasis during disease progression, we generated a spatial transcriptomics dataset of skeletal muscle in the SOD1[G93A] mouse model of ALS. Using this strategy, we identified polyamine metabolism as one of the main altered pathways in affected muscle fibers. By establishing a correlation between the vulnerability of muscle fibers and the dysregulation of this metabolic pathway, we show that disrupting polyamine homeostasis causes impairments similar to those seen in ALS muscle. Finally, we show that restoration of polyamine homeostasis rescues the muscle phenotype in SOD1[G93A] mice, opening new perspectives for the treatment of ALS.}, } @article {pmid39931973, year = {2025}, author = {Xu, C and Diemant, T and Zhang, S and Liu, X and Passerini, S}, title = {Enhanced Cathode-Electrolyte Interphase for Prolonged Cycling Stability of Aluminum-Selenium Batteries Using Locally Concentrated Ionic Liquid Electrolytes.}, journal = {Angewandte Chemie (International ed. in English)}, volume = {64}, number = {17}, pages = {e202500041}, pmid = {39931973}, issn = {1521-3773}, support = {//China Sponsorship Council/ ; //China Scholarship Council/ ; //Helmholtz Association/ ; Start-up Research Fund of Southeast University4003002418//Start-up Research Fund of Southeast University/ ; }, abstract = {Al-Se batteries (ASeBs) with high theoretical specific capacity and discharge voltage are promising energy storage devices. However, the detrimental shuttle effect occurring in conventional ionic liquid electrolytes (ILEs) challenges their development. Herein, a thicker cathode/electrolyte interphase (CEI) is constructed via employing locally concentrated IL electrolytes (LCILEs) to overcome these issues. It is demonstrated that LCILEs facilitate the incorporation of Emim[+] into the electrode/electrolyte interphases, and, meanwhile, more Al-Cl species deposits are observed in the CEI. The formed CEI effectively prevents the dissolution of poly-selenides, inhibiting their related parasitic reactions. These result in ASeBs, employing the LCILE, to deliver a specific discharge capacity of 218 mAh g[-1] at 0.5 A g[-1] after 100 cycles at 20 °C, while the cell using the neat ILE only maintains 38 mAh g[-1] under the same conditions. Moreover, an Al-S cell operated in LCILEs reaches 578 mAh g[-1] at 0.1 A g[-1] after 150 cycles, which is also significantly better than 317 mAh g[-1] in the neat ILE. This study provides an LCILE-based strategy to reinforce the CEI in order to suppress the shuttle effect, realizing Al-chalcogen batteries with better performance.}, } @article {pmid39930680, year = {2025}, author = {Guzanova, EV and Sorokina, TA and Zorkova, AV}, title = {[Nutritional care for patients with neurodegenerative diseases in the outpatient practice of a neurologist].}, journal = {Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova}, volume = {125}, number = {1}, pages = {76-83}, doi = {10.17116/jnevro202512501176}, pmid = {39930680}, issn = {1997-7298}, mesh = {Humans ; *Ambulatory Care ; *Amyotrophic Lateral Sclerosis/complications ; *Dehydration/etiology/diagnosis/therapy ; Enteral Nutrition ; *Malnutrition/etiology/diagnosis/therapy ; *Neurodegenerative Diseases/complications ; Neurologists ; }, abstract = {Nutrition is a basic factor of health and well-being of people, affecting the quality and duration of life. Meanwhile, patients with neurodegenerative diseases of the central nervous system are particularly at risk of malnutrition and dehydration with serious health consequences. The article presents an analysis of the main causes of malnutrition in patients with neurodegenerative diseases, and considers a clinical case of including additional nutritional support in the comprehensive management of a patient with amyotrophic lateral sclerosis. The importance of screening elderly patients for the risks of malnutrition and dehydration during an outpatient medical appointment and including appropriate additional diagnostic and therapeutic (additional enteral nutrition and fluid regimen) measures in the work of an outpatient neurologist is emphasized.}, } @article {pmid39929612, year = {2025}, author = {Chen, BL and Lu, JZ and Zhou, XM and Wen, XD and Jiang, YJ and Luo, N}, title = {[Mechanism of Daotan Xixin Decoction in treating APP/PS1 mice based on high-throughput sequencing technology and bioinformatics analysis].}, journal = {Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica}, volume = {50}, number = {2}, pages = {301-313}, doi = {10.19540/j.cnki.cjcmm.20241011.401}, pmid = {39929612}, issn = {1001-5302}, mesh = {Animals ; *Drugs, Chinese Herbal/administration & dosage ; Mice ; Male ; *Alzheimer Disease/drug therapy/genetics/metabolism ; Computational Biology ; Mice, Inbred C57BL ; High-Throughput Nucleotide Sequencing ; *Amyloid beta-Protein Precursor/genetics/metabolism ; Hippocampus/drug effects/metabolism ; Mice, Transgenic ; *Presenilin-1/genetics/metabolism ; Humans ; Memory/drug effects ; Maze Learning/drug effects ; Amyloid beta-Peptides/metabolism/genetics ; Disease Models, Animal ; }, abstract = {This study aims to investigate the therapeutic effect and mechanism of Daotan Xixin Decoction on APP/PS1 mice. Twelve APP/PS1 male mice were randomized into four groups: APP/PS1 and low-, medium-, and high-dose Daotan Xixin Decoction. Three C57BL/6 wild-type mice were used as the control group. The learning and memory abilities of mice in each group were examined by the Morris water maze test. The pathological changes of hippocampal nerve cells were observed by hematoxylin-eosin staining and Nissl staining. Immunohistochemistry was employed to detect the expression of β-amyloid(Aβ)_(1-42) in the hippocampal tissue. The high-dose Daotan Xixin Decoction group with significant therapeutic effects and the model group were selected for high-throughput sequencing. The differentially expressed gene(DEG) analysis, Gene Ontology(GO) analysis, Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis, and Gene Set Variation Analysis(GSVA) were performed on the sequencing results. RT-qPCR and Western blot were conducted to determine the mRNA and protein levels, respectively, of some DEGs. Compared with the APP/PS1 group, Daotan Xixin Decoction at different doses significantly improved the learning and memory abilities of APP/PS1 mice, ameliorated the neuropathological damage in the CA1 region of the hippocampus, increased the number of neurons, and decreased the deposition of Aβ_(1-42) in the brain. A total of 1 240 DEGs were screened out, including 634 genes with up-regulated expression and 606 genes with down-regulated expression. The GO analysis predicted the biological processes including RNA splicing and protein folding, the cellular components including spliceosome complexes and nuclear spots, and the molecular functions including unfolded protein binding and heat shock protein binding. The KEGG pathway enrichment analysis revealed the involvement of neurodegenerative disease pathways, amyotrophic lateral sclerosis, and splicing complexes. Further GSVA pathway enrichment analysis showed that the down-regulated pathways involved nuclear factor-κB(NF-κB)-mediated tumor necrosis factor-α(TNF-α) signaling pathway, UV response, and unfolded protein response, while the up-regulated pathways involved the Wnt/β-catenin signaling pathway. The results of RT-qPCR and Western blot showed that compared with the APP/PS1 group, Daotan Xixin Decoction at different doses down-regulated the mRNA and protein levels of signal transducer and activator of transcription 3(STAT3), NF-κB, and interleukin-6(IL-6) in the hippocampus. In conclusion, Daotan Xixin Decoction can improve the learning and memory abilities of APP/PS1 mice by regulating the STAT3/NF-κB/IL-6 signaling pathway.}, } @article {pmid39929585, year = {2025}, author = {Huang, M and Stremlau, M and Zavras, J and Zivko, C and Thomas, AG and Pietri, P and Machairaki, V and Slusher, BS}, title = {Neutral sphingomyelinase 2: A promising drug target for CNS disease.}, journal = {Advances in pharmacology (San Diego, Calif.)}, volume = {102}, number = {}, pages = {65-101}, pmid = {39929585}, issn = {1557-8925}, support = {P30 MH075673/MH/NIMH NIH HHS/United States ; R01 AG063831/AG/NIA NIH HHS/United States ; R01 AG084728/AG/NIA NIH HHS/United States ; }, mesh = {Humans ; *Sphingomyelin Phosphodiesterase/metabolism/antagonists & inhibitors ; Animals ; *Central Nervous System Diseases/drug therapy/enzymology/metabolism ; *Enzyme Inhibitors/pharmacology/therapeutic use ; }, abstract = {Neutral sphingomyelinase 2 (nSMase2), encoded by the SMPD3 gene, is a pivotal enzyme in sphingolipid metabolism, hydrolyzing sphingomyelin to produce ceramide, a bioactive lipid involved in apoptosis, inflammation, membrane structure, and extracellular vesicle (EV) biogenesis. nSMase2 is abundantly expressed in the central nervous system (CNS), particularly in neurons, and its dysregulation is implicated in pathologies such as Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), prion diseases, and neuroviral diseases. In this review, we discuss the critical role of nSMase2 in the CNS and its involvement in neurological as well as non-neurological diseases. We explore the enzyme's functions in sphingolipid metabolism, its regulatory mechanisms, and the implications of its dysregulation in disease pathogenesis. The chapter highlights the therapeutic potential of pharmacologically targeting nSMase2 with small molecule inhibitors and emphasizes the need for further research to optimize inhibitor specificity and efficacy for clinical applications. By understanding the multifaceted roles of nSMase2, we aim to provide insights into novel therapeutic strategies for treating complex diseases associated with its dysregulation.}, } @article {pmid39929580, year = {2025}, author = {Matheoudakis, K and O'Connor, JJ}, title = {Modulatory and protective effects of prolyl hydroxylase domain inhibitors in the central nervous system.}, journal = {Advances in pharmacology (San Diego, Calif.)}, volume = {102}, number = {}, pages = {211-235}, doi = {10.1016/bs.apha.2024.10.006}, pmid = {39929580}, issn = {1557-8925}, mesh = {Humans ; Animals ; *Prolyl-Hydroxylase Inhibitors/pharmacology/therapeutic use ; *Neuroprotective Agents/pharmacology/therapeutic use ; *Central Nervous System/drug effects/metabolism ; }, abstract = {Oxygen is essential for all mammalian species, with complex organs such as the brain requiring a large and steady supply to function. During times of low or inadequate oxygen supply (hypoxia), adaptation is required in order to continue to function. Hypoxia inducible factors (HIF) are transcription factors which are activated during hypoxia and upregulate protective genes. Normally, when oxygen levels are sufficient (normoxia) HIFs are degraded by oxygen sensing prolyl hydroxylase domain proteins (PHD), but during hypoxia PHDs no longer exert influence on HIFs allowing their activation. Given that PHDs regulate the activity of HIFs, their pharmacological inhibition through PHD inhibitors (PHDIs) is believed to be the basis of their neuroprotective benefits. This review discusses some of the potential therapeutic benefits of PHDIs in a number of neurological disorders which see hypoxia as a major pathophysiological mechanism. These include stroke, Parkinson's disease, and amyotrophic lateral sclerosis. We also explore the potential neuroprotective benefits and limitations of PHDIs in a variety of disorders in the central nervous system (CNS). Additionally, the activation of HIFs by PHDIs can have modulatory effects on CNS functions such as neurotransmission and synaptic plasticity, mechanisms critical to cognitive processes such as learning and memory.}, } @article {pmid39929112, year = {2025}, author = {Zhao, H and Liu, L and Zeng, Y and Nie, X and Wang, J and Bai, L and Pan, L}, title = {Identification of metabolic enzyme genes linked to mesosulfuron-methyl resistance in Bromus japonicus.}, journal = {Plant physiology and biochemistry : PPB}, volume = {221}, number = {}, pages = {109609}, doi = {10.1016/j.plaphy.2025.109609}, pmid = {39929112}, issn = {1873-2690}, mesh = {*Sulfonylurea Compounds/pharmacology ; *Herbicide Resistance/genetics ; Acetolactate Synthase/genetics/metabolism/antagonists & inhibitors ; *Herbicides/pharmacology ; *Plant Proteins/genetics/metabolism ; Gene Expression Regulation, Plant/drug effects ; *Genes, Plant ; Cytochrome P-450 Enzyme System/genetics/metabolism ; }, abstract = {Bromus japonicus is a very troublesome weed in major winter wheat fields in China and substantially reduces wheat yield. Resistance to acetolactate synthase (ALS)-inhibiting herbicides in B. japonicus has become increasingly prevalent in recent years. While the mechanism of target site resistance (TSR) to ALS-inhibiting herbicides in B. japonicus has been well elucidated, the understanding of non-target site resistance (NTSR) remains limited. In this study, we identified a B. japonicus population (BJ-NTSR-1) which has developed resistance to mesosulfuron-methyl. Compared to the mesosulfuron-methyl-susceptible population (BJ-S), the resistance level of BJ-NTSR-1 was found to be 22.56 times higher. Based on the results of ALS gene sequencing and relative expression analyses, TSR was not detected in the BJ-NTSR-1 population. Additionally, pretreatment with cytochrome P450 (CYP450) and glutathione S-transferase (GST) inhibitors did not reverse the resistance to mesosulfuron-methyl in BJ-NTSR-1 population. RNA-seq and RT-qPCR analyses revealed that, three uridine 5'-diphospho-glucosyl transferase (UGT) genes (UGT76F1, UGT88F5, and UGT85A1), four ATP-binding cassette (ABC) transporter genes (ABCB19s, ABCG1, and ABCB21), and three CYP450 genes (CYP71C1, CYP71C2, and CYP72A15) are significantly upregulated in the BJ-NTSR-1 population. Among these genes, the overexpression of ABCG1 enhanced yeast resistance to mesosulfuron-methyl. These genes are likely involved in mediating NTSR to mesosulfuron-methyl in the BJ-NTSR-1 population. This study presents the first global report that CYP450, UGT, and ABC transporter genes may collectively mediate NTSR to ALS-inhibiting herbicides in Brome species.}, } @article {pmid39928509, year = {2025}, author = {Scafide, KN and Arundel, L and Assas, G and King, EL}, title = {Pressure injury detection using alternate light: a proof-of-concept study.}, journal = {Journal of wound care}, volume = {34}, number = {Sup2}, pages = {S17-S23}, doi = {10.12968/jowc.2023.0304}, pmid = {39928509}, issn = {0969-0700}, mesh = {Humans ; *Pressure Ulcer/diagnosis ; Male ; Female ; Proof of Concept Study ; Middle Aged ; Aged ; *Light ; Adult ; Skin Pigmentation ; Aged, 80 and over ; }, abstract = {OBJECTIVE: Identification of early-stage pressure injuries (PIs) during visual skin assessment may be subjective and unreliable. An alternate light source (ALS) has been shown to increase the probability of detecting evidence of bruises on individuals with darker skin tones. Bruises and early-stage PIs are often difficult to identify, especially in those with darker skin tones, where melanin concentration is high. Given the effect skin pigmentation has on detecting both types of cutaneous injuries, this proof-of-concept study aimed to describe the characteristics of Stage 1 PIs and deep tissue PIs as viewed under an ALS.

METHOD: Eligible participants were first examined by a certified wound ostomy continence nurse using environmentally available white light. A blinded second examiner then evaluated the size of the potential tissue impairment using violet (406nm) and blue (448nm) ALS viewed through yellow and orange goggles, respectively. Portable ultrasound was used to confirm tissue involvement. Data were summarised using descriptive statistics.

RESULTS: The study included 10 participants (40% of whom were from minority racial/ethnic groups) with a mean Braden Scale score of 11.1. The majority of PIs (80%) involved deep tissue and were located on lower extremities (60%). The median PI size was larger by 17.5cm[2] and 13.7cm[2], respectively, using ALS compared with white light when viewed under violet and blue wavelengths. Ultrasound data were limited to non-extremity regions (n=3 participants) with hypoechoic areas noted as being 10-13mm in thickness and up to 16.7mm deep.

CONCLUSION: Evidence of tissue damage that extended beyond that visualised under white light was noted with ALS. Usefulness of ultrasound was limited over bony prominences where there was too little subcutaneous tissue. Further research is warranted to investigate the potential application of ALS for the early detection of PIs.}, } @article {pmid39928236, year = {2025}, author = {Kaspute, G and Ramanavicius, A and Prentice, U}, title = {Natural drug delivery systems for the treatment of neurodegenerative diseases.}, journal = {Molecular biology reports}, volume = {52}, number = {1}, pages = {217}, pmid = {39928236}, issn = {1573-4978}, support = {S-MIP-24-111//Research Council of Lithuania (LMTLT)/ ; }, mesh = {Humans ; *Neurodegenerative Diseases/drug therapy ; *Drug Delivery Systems/methods ; Blood-Brain Barrier/metabolism/drug effects ; Animals ; *Biological Products/therapeutic use/administration & dosage ; Nanoparticles/chemistry ; Liposomes ; Anti-Inflammatory Agents ; Biological Availability ; }, abstract = {Today, herbal drugs are prominent in the pharmaceutical industry due to their well-known therapeutic and side effects. Plant-based compounds often face limitations such as poor solubility, low bioavailability, and instability in physiological environments, restricting their therapeutic efficacy and delivery. Nanotechnology-based solutions, including nanoparticle formulations and advanced delivery systems like liposomes and transfersomes, address these issues by enhancing solubility, stability, bioavailability, and targeted delivery, thereby optimizing the therapeutic potential of phytoactive compounds. Neuroinflammation can be a cause of neurodegenerative disorders such as Alzheimer's and Parkinson's diseases, or amyotrophic lateral sclerosis. Consequently, there is a need for the optimal delivery of a pharmacological anti-inflammatory agents to the CNS. Thus, the non-invasive administration of a stable compound at a therapeutic concentration is needed to assure molecule crossing through the blood-brain barrier. Natural resources have more structural diversity and novelty than synthetic compounds, e.g. plant-derived drug products have higher molecular weights, incorporate more oxygen atoms, and are more complex. As a result, plant-derived products have unique features which can be used to effectively modulate neuroinflammation. Therefore, this review aims to identify herbal molecules capable of targeting neuroinflammation and present novel strategies for their efficient delivery.}, } @article {pmid39927436, year = {2025}, author = {}, title = {Novel Biomarkers of FTD-ALS.}, journal = {The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry}, volume = {31}, number = {1}, pages = {6}, doi = {10.1177/10738584241308752}, pmid = {39927436}, issn = {1089-4098}, } @article {pmid39926223, year = {2025}, author = {Moore, S and Donlon, NE}, title = {Improving gastrointestinal scoring systems for predicting short-term mortality in critically ill patients.}, journal = {World journal of gastroenterology}, volume = {31}, number = {5}, pages = {102622}, pmid = {39926223}, issn = {2219-2840}, mesh = {Humans ; *Critical Illness/mortality ; *Gastrointestinal Diseases/mortality/diagnosis ; Intensive Care Units/statistics & numerical data ; Retrospective Studies ; Severity of Illness Index ; Prognosis ; Hospital Mortality ; Predictive Value of Tests ; Risk Assessment/methods ; }, abstract = {Shen et al's retrospective study aims to compare the utility of two separate scoring systems for predicting mortality attributable to gastrointestinal (GI) injury in critically ill patients [the GI Dysfunction Score (GIDS) and the Acute Gastrointestinal Injury (AGI) grade]. The authors note that this study is the first proposal that suggests an equivalence between the ability of both scores to predict mortality at 28 days from intensive care unit (ICU) admission. Shen et al retrospectively analysed an ICU cohort of patients utilising two physicians administering both the AGI grade and GIDS score, using electronic healthcare records and ICU flowsheets. Where these physicians disagreed about the scores, the final decision as to the scores was made by an associate chief physician, or chief physician. We note that the primary reason for the development of GIDS was to create a clear score for GI dysfunction, with minimal subjectivity or inter-operator variability. The subjectivity inherent to the older AGI grading system is what ultimately led to the development of GIDS in 2021. By ensuring consensus between physicians administering the AGI, Shen et al have controlled for one of this grading systems biggest issues. We have concerns, however, that this does not represent the real-world challenges associated with applying the AGI compared to the newer GIDS, and wonder if this arbitration process had not been instituted, would the two scoring systems remain equivalent in terms of predicted mortality?}, } @article {pmid39924298, year = {2025}, author = {Malouin-Lachance, A and Capolupo, J and Laplante, C and Hudon, A}, title = {Does the Digital Therapeutic Alliance Exist? Integrative Review.}, journal = {JMIR mental health}, volume = {12}, number = {}, pages = {e69294}, pmid = {39924298}, issn = {2368-7959}, mesh = {Humans ; *Digital Health ; *Mental Disorders/therapy ; *Artificial Intelligence ; *Psychotherapy/methods ; *Therapeutic Alliance ; }, abstract = {BACKGROUND: Mental health disorders significantly impact global populations, prompting the rise of digital mental health interventions, such as artificial intelligence (AI)-powered chatbots, to address gaps in access to care. This review explores the potential for a "digital therapeutic alliance (DTA)," emphasizing empathy, engagement, and alignment with traditional therapeutic principles to enhance user outcomes.

OBJECTIVE: The primary objective of this review was to identify key concepts underlying the DTA in AI-driven psychotherapeutic interventions for mental health. The secondary objective was to propose an initial definition of the DTA based on these identified concepts.

METHODS: The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) for scoping reviews and Tavares de Souza's integrative review methodology were followed, encompassing systematic literature searches in Medline, Web of Science, PsycNet, and Google Scholar. Data from eligible studies were extracted and analyzed using Horvath et al's conceptual framework on a therapeutic alliance, focusing on goal alignment, task agreement, and the therapeutic bond, with quality assessed using the Newcastle-Ottawa Scale and Cochrane Risk of Bias Tool.

RESULTS: A total of 28 studies were identified from an initial pool of 1294 articles after excluding duplicates and ineligible studies. These studies informed the development of a conceptual framework for a DTA, encompassing key elements such as goal alignment, task agreement, therapeutic bond, user engagement, and the facilitators and barriers affecting therapeutic outcomes. The interventions primarily focused on AI-powered chatbots, digital psychotherapy, and other digital tools.

CONCLUSIONS: The findings of this integrative review provide a foundational framework for the concept of a DTA and report its potential to replicate key therapeutic mechanisms such as empathy, trust, and collaboration in AI-driven psychotherapeutic tools. While the DTA shows promise in enhancing accessibility and engagement in mental health care, further research and innovation are needed to address challenges such as personalization, ethical concerns, and long-term impact.}, } @article {pmid39923073, year = {2025}, author = {Wang, Z and Yin, Z and Sun, G and Zhang, D and Zhang, J}, title = {Genetic evidence for the liver-brain axis: lipid metabolism and neurodegenerative disease risk.}, journal = {Lipids in health and disease}, volume = {24}, number = {1}, pages = {41}, pmid = {39923073}, issn = {1476-511X}, mesh = {Humans ; *Lipid Metabolism/genetics ; Genome-Wide Association Study ; *Liver/metabolism/pathology ; Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology ; *Brain/metabolism/pathology ; Mendelian Randomization Analysis ; *Neurodegenerative Diseases/genetics/metabolism/pathology ; Parkinson Disease/genetics/metabolism/pathology ; Cholesterol, LDL/blood/genetics ; Alzheimer Disease/genetics/pathology/metabolism ; Polymorphism, Single Nucleotide ; Genetic Predisposition to Disease ; Risk Factors ; Multiple Sclerosis/genetics/metabolism/pathology ; Male ; Female ; Cholesterol/blood ; }, abstract = {BACKGROUND: The liver‒brain axis is critical in neurodegenerative diseases (NDs), with lipid metabolism influencing neuroinflammation and microglial function. A systematic investigation of the genetic relationship between lipid metabolism abnormalities and ND, namely, Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS), is lacking. To assess potential causal links between ND and six lipid parameters, two-sample Mendelian randomization (MR) was used.

METHODS: Large-scale European ancestry GWAS data for lipid parameters and ND (AD, ALS, PD, and MS) were used. Genetic variants demonstrating significant correlations (P < 5 × 10[-8]) with lipid metabolism parameters were identified and employed as instrumental variables (IVs) after proper validation. The research incorporated UK Biobank genomic data to examine associations between genetic variants and lipid metabolism parameters. The analysis included primary MR, sensitivity analyses, and multivariable MR, which considered potential mediators.

RESULTS: MR via the inverse-variance weighted method revealed causal effects of cholesterol (CHOL, OR = 1.10, 95% CI: 1.03-1.18, P = 4.23 × 10⁻[3]) and low-density lipoprotein cholesterol (LDLC, OR = 1.10, 95% CI: 1.03-1.17, P = 3.28 × 10⁻[3]) on the risk of ALS, which were validated across multiple methods. Potential correlations were observed between ApoB and ALS and inversely correlated with AD, whereas no significant associations were found for PD or MS. CHOL and LDLC associations with ALS demonstrated no significant heterogeneity or pleiotropy, supporting their reliability.

CONCLUSIONS: Higher CHOL and LDLC levels were associated with increased ALS risk, suggesting a potential causal link, and supporting the liver‒brain axis hypothesis in ND. Current genetic evidence does not support a significant role for lipid metabolism in PD and MS etiology, suggesting the relationship between lipid metabolism and other NDs may be more complex and warrants further investigation.}, } @article {pmid39922547, year = {2025}, author = {Rossi, S and Milani, M and Della Valle, I and Apolloni, S}, title = {Transcriptomic profiling of symptomatic and end-stage SOD1-G93A transgenic mice reveals extracellular matrix components as key players in ALS pathogenesis.}, journal = {Biochimica et biophysica acta. Molecular basis of disease}, volume = {1871}, number = {4}, pages = {167707}, doi = {10.1016/j.bbadis.2025.167707}, pmid = {39922547}, issn = {1879-260X}, } @article {pmid39922366, year = {2025}, author = {Kopalli, SR and Behl, T and Kyada, A and Rekha, MM and Kundlas, M and Rani, P and Nathiya, D and Satyam Naidu, K and Gulati, M and Bhise, M and Gupta, P and Wal, P and Fareed, M and Ramniwas, S and Koppula, S and Gasmi, A}, title = {Synaptic plasticity and neuroprotection: The molecular impact of flavonoids on neurodegenerative disease progression.}, journal = {Neuroscience}, volume = {569}, number = {}, pages = {161-183}, doi = {10.1016/j.neuroscience.2025.02.007}, pmid = {39922366}, issn = {1873-7544}, mesh = {Humans ; *Neuronal Plasticity/drug effects/physiology ; *Flavonoids/pharmacology/therapeutic use ; Animals ; *Neurodegenerative Diseases/drug therapy/metabolism ; *Neuroprotective Agents/pharmacology/therapeutic use ; *Neuroprotection/drug effects/physiology ; Signal Transduction/drug effects ; Disease Progression ; }, abstract = {Flavonoids are a broad family of polyphenolic chemicals that are present in a wide variety of fruits, vegetables, and medicinal plants. Because of their neuroprotective qualities, flavonoids have attracted a lot of interest. The potential of flavonoids to control synaptic plasticity-a crucial process underlying memory, learning, and cognitive function-is becoming more and more clear. Dysregulation of synaptic plasticity is a feature of neurodegenerative diseases such as amyotrophic lateral sclerosis (0.4 %), Parkinson's (1-2 %), Alzheimer's (5-7 %), and Huntington's ((0.2 %)). This review discusses the molecular mechanisms via which flavonoids influence synaptic plasticity as well as their therapeutic potential in neurodegenerative diseases. Flavonoids modulate key signaling pathways such as MAPK/ERK and PI3K/Akt/mTOR to support neuroprotection, synaptic plasticity, and neuronal health, while also influencing neurotrophic factors (BDNF, NGF) and their receptors (TrkB, TrkA). They regulate neurotransmitter receptors like GABA, AMPA, and NMDA to balance excitatory and inhibitory transmission, and exert antioxidant effects via the Nrf2-ARE pathway and anti-inflammatory actions by inhibiting NF-κB signaling, highlighting their potential for treating neurodegenerative diseases. These varied reactions support the preservation of synapse function and neuronal integrity in the face of neurodegenerative insults. Flavonoids can reduce the symptoms of neurodegeneration, prevent synaptic loss, and enhance cognitive function, according to experimental studies. However, there are still obstacles to using these findings in clinical settings, such as limited bioavailability and the need for consistent dose. The focus of future research should be on improving flavonoid delivery systems and combining them with conventional medications.}, } @article {pmid39921200, year = {2025}, author = {Shiozumi, T and Matsuyama, T and Nishioka, N and Kiguchi, T and Kitamura, T and Ohta, B and Iwami, T}, title = {Evaluation of interventions in prehospital and in-hospital settings and outcomes for out-of-hospital cardiac arrest patients meeting the termination of resuscitation rule in Japan: A nationwide database study (The JAAM-OHCA Registry).}, journal = {Resuscitation}, volume = {208}, number = {}, pages = {110530}, doi = {10.1016/j.resuscitation.2025.110530}, pmid = {39921200}, issn = {1873-1570}, mesh = {Humans ; *Out-of-Hospital Cardiac Arrest/therapy/mortality ; Japan/epidemiology ; Male ; Female ; Retrospective Studies ; Registries ; *Emergency Medical Services/statistics & numerical data/methods ; Aged ; *Cardiopulmonary Resuscitation/methods/statistics & numerical data ; Middle Aged ; Airway Management/statistics & numerical data ; Databases, Factual ; Epinephrine/administration & dosage ; Aged, 80 and over ; Advanced Cardiac Life Support/statistics & numerical data ; }, abstract = {BACKGROUND: Out-of-hospital cardiac arrest (OHCA) is a global health burden with low survival rates. The termination of resuscitation (TOR) rule, widely adopted internationally, aims to preserve dignity, optimize resources, and protect healthcare providers. However, prehospital TOR is not implemented in Japan, presenting legal and practical challenges. This study analyzes temporal trends in prehospital and in-hospital interventions for OHCA patients with poor predicted outcomes.

METHODS: This retrospective study analyzed data from the Japanese Association for Acute Medicine Out-of-Hospital Cardiac Arrest (JAAM-OHCA) registry (June 2014-December 2021). Adult OHCA patients with medical causes were included if they fulfilled all the advanced life support (ALS) TOR rule criteria: unwitnessed arrest, no return of spontaneous circulation, no bystander-initiated cardiopulmonary resuscitation, and no automated external defibrillator use or defibrillation. Prehospital and in-hospital interventions were evaluated.

RESULTS: Among 11,334 patients meeting the inclusion criteria, 2,447 received all three ALS interventions (advanced airway management, intravenous access, and epinephrine administration). Over time, in-hospital interventions, including endotracheal intubation (56%) and epinephrine administration (82%), decreased, while advanced therapies, including coronary angiography, extracorporeal membrane oxygenation, and targeted temperature management, remained rare (<1%). The median time to TOR after hospital arrival shortened to 18 min. In contrast, prehospital epinephrine administration increased, while advanced airway management and intravenous access decreased.

CONCLUSIONS: OHCA patients who met TOR rule showed a decrease in in-hospital interventions. Further efforts are warranted to avoid futile medical treatments and promote patient-centered care.}, } @article {pmid39920775, year = {2025}, author = {Yousefian-Jazi, A and Kim, S and Chu, J and Choi, SH and Nguyen, PTT and Park, U and Kim, MG and Hwang, H and Lee, K and Kim, Y and Hyeon, SJ and Rhim, H and Ryu, HL and Lim, G and Stein, TD and Lim, K and Ryu, H and Lee, J}, title = {Loss of MEF2C function by enhancer mutation leads to neuronal mitochondria dysfunction and motor deficits in mice.}, journal = {Molecular neurodegeneration}, volume = {20}, number = {1}, pages = {16}, pmid = {39920775}, issn = {1750-1326}, support = {R01NS109537//NIH R01/ ; 2E30954//KIST Grant/ ; HU23C0217//Korea Dementia Research Project Grant/ ; 2022R1A2C3013138//National Research Foundation/ ; R01 NS109537/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; *Mitochondria/metabolism/genetics/pathology ; Mice ; *MEF2 Transcription Factors/genetics ; Humans ; *Motor Neurons/metabolism/pathology ; *Amyotrophic Lateral Sclerosis/genetics/metabolism ; Mutation/genetics ; HEK293 Cells ; Disease Models, Animal ; Enhancer Elements, Genetic/genetics ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by the loss of both upper and lower motor neurons, leading to progressive paralysis. Both genetic alterations and epigenetic modifications contribute to neuronal dysfunction in the pathogenesis of ALS. However, the mechanism behind genetic mutations in the non-coding region of genes that affect epigenetic modifications remains unclear.

METHODS: Convolutional neural network was used to identify an ALS-associated SNP located in the intronic region of MEF2C (rs304152), residing in a putative enhancer element. To examine the alteration of MEF2C transcription by the SNP, we generated HEK293T cells carrying the major or minor allele by CRISPR-Cas9. To verify the role of MEF2C-knockdown (MEF2C-KD) in mice, we developed AAV expressing shRNA for MEF2C based on AAV-U6 promoter vector. Neuropathological alterations of MEF2C-KD mice with mitochondrial dysfunction and motor neuronal damage were observed by confocal microscopy and transmission electron microscope (TEM). Behavioral changes of mice were examined through longitudinal study by tail suspension, inverted grid test and automated gait analysis.

RESULTS: Here, we show that enhancer mutation of MEF2C reduces own gene expression and consequently impairs mitochondrial function in motor neurons. MEF2C localizes and binds to the mitochondria DNA, and directly modulates mitochondria-encoded gene expression. CRISPR/Cas-9-induced mutation of the MEF2C enhancer decreases expression of mitochondria-encoded genes. Moreover, MEF2C mutant cells show reduction of mitochondrial membrane potential, ATP level but elevation of oxidative stress. MEF2C deficiency in the upper and lower motor neurons of mice impairs mitochondria-encoded genes, and leads to mitochondrial metabolic disruption and progressive motor behavioral deficits.

CONCLUSIONS: Together, MEF2C dysregulation by the enhancer mutation leads to mitochondrial dysfunction and oxidative stress, which are prevalent features in motor neuronal damage and ALS pathogenesis. This genetic and epigenetic crosstalk mechanism provides insights for advancing our understanding of motor neuron disease and developing effective treatments.}, } @article {pmid39920055, year = {2025}, author = {Ramsden, V and McInnes, E and Wilson, P and Babl, FE and Kuhn, L and Cowie, J and Campbell, P and Middleton, S and Wilson, C and Straiton, N and Tavender, E}, title = {Sustainability of healthcare system improvements, programmes and interventions in acute care settings: protocol for a mixed methods systematic review.}, journal = {BMJ open}, volume = {15}, number = {2}, pages = {e094174}, pmid = {39920055}, issn = {2044-6055}, mesh = {Humans ; Systematic Reviews as Topic ; *Delivery of Health Care/standards/organization & administration ; *Quality Improvement ; Research Design ; Program Evaluation ; }, abstract = {INTRODUCTION: Sustaining evidence-based care is challenging in all clinical settings. Acute care settings have a unique set of contextual factors that may impact sustainability (eg, fast-paced, regular staff turnover). Much of the previous research explores sustainability across undifferentiated healthcare settings making it difficult to determine factors that influence sustainability in acute care settings. The aim of this review is to identify facilitators and barriers that influence the delivery of sustained healthcare interventions (eg, integration of clinical guidelines) within adult and paediatric hospital-based acute care settings.

METHODS AND ANALYSIS: A mixed methods systematic review updating Cowie et al's (which included studies from 2008 to 2017) previously published systematic review will be conducted. The following databases will be searched: Medline, Embase, Cochrane Database of Systematic Reviews, CINAHL and Allied and Complementary Medicine (AMED), from November 2017 to the present for studies published in English. Relevant reference lists of included studies will be manually searched. Empirical quantitative and qualitative studies that report the sustainability of an intervention or programme in acute care settings using a theoretical framework(s), model(s) or theory(ies) to explore facilitators and barriers, will be included. Studies will be exported into Covidence (Melbourne) and pairs of reviewers will independently screen abstracts and full-text studies. The discussion will be used to resolve any disagreements and a third coauthor enlisted should a consensus not be reached. Two independent coauthors will extract key study characteristics and assess each study's quality. Data will be extracted using Covidence (Melbourne). Evidence tables will be used to present descriptive data. Facilitators and barriers will be mapped to the Consolidated Framework for Sustainability Constructs in Healthcare and a narrative approach will be used to present key findings.

ETHICS AND DISSEMINATION: No primary data will be collected so formal ethical approval is not required. Findings will be disseminated through peer-reviewed publications, presented at international conferences and on social media.

PROSPERO REGISTRATION NUMBER: PROSPERO CRD42024547535.}, } @article {pmid39918735, year = {2025}, author = {Wentzel, A and Smith, W and Jansen van Vuren, E and Kruger, R and Breet, Y and Wonkam-Tingang, E and Hanchard, NA and Chung, ST}, title = {Allostatic load and cardiometabolic health in a young adult South African population: the African-PREDICT study.}, journal = {American journal of physiology. Heart and circulatory physiology}, volume = {328}, number = {3}, pages = {H581-H593}, doi = {10.1152/ajpheart.00845.2024}, pmid = {39918735}, issn = {1522-1539}, support = {//HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)/ ; //South African Medical Research Council (SAMRC)/ ; //South African National Research Foundation (SA-NRF)/ ; //Newton Fund (NF)/ ; //Pfizer (South Africa)/ ; //Boeringer-Ingelheim (South Africa)/ ; //Norvatis (South Africa)/ ; //MediClinic Hospital Group (South Africa)/ ; //Roche Holding | Roche Diagnostics (Roche Diagnostics Corporation)/ ; }, mesh = {Humans ; *Allostasis ; Male ; Female ; South Africa/epidemiology ; Adult ; Young Adult ; Prospective Studies ; Cardiometabolic Risk Factors ; *Hypertension/physiopathology/epidemiology/diagnosis/blood ; *Cardiovascular Diseases/physiopathology/epidemiology/diagnosis/blood ; Biomarkers/blood ; Age Factors ; Risk Assessment ; *Prediabetic State/epidemiology/physiopathology/diagnosis/blood ; Blood Pressure ; *Stress, Psychological/physiopathology/epidemiology/diagnosis/blood ; Inflammation Mediators/blood ; }, abstract = {Sustained stress, assessed as a high allostatic load score (ALS), is an independent cardiovascular disease (CVD) risk factor in older adults but its associations in young people are undefined. Since neurological maturation impacts stress adaptation and CVD risk, we assessed the relationship of ALS with CVD profile by using a tiered approach stratified by age [emerging adults (EA) aged 20-24 yr vs. young adults (YA) aged 25-30 yr] and ALS (high vs. low). In 1,054 healthy participants of the African Prospective Study on Early Detection and Identification of Cardiovascular Disease and Hypertension (African-PREDICT), we determined: 1) ALS in EA versus YA; 2) the relationship between ALS and cardiovascular (CV) health, and 3) the odds of high ALS > 4 to identify masked hypertension (HT) and prediabetes as cardiometabolic outcomes. A nine-component, four-domain ALS was compiled: neuroendocrine [dehydroepiandrosterone (DHEA), cortisol], inflammatory [interleukin-6 (IL-6), C-reactive protein (CRP)], cardiovascular [systolic blood pressure (SBP) and diastolic blood pressure (DBP)], and metabolic [total cholesterol, high density lipoprotein cholesterol (HDL-cholesterol), body mass index (BMI)]. Retinal vessel caliber, pulse wave velocity (PWV), and cardiac structure and function were assessed. Median ALS was 3 (range: 1-9). A high-ALS > 4 was more common in YA versus EA (47 vs. 35%, P = 0.032). Higher ALS associated with narrower retinal arteries (P < 0.01), greater PWV (P ≤ 0.01), lower diastolic function (P < 0.01), and left ventricular (LV) function (P < 0.01). High-ALS increased the odds of having masked hypertension, prediabetes, narrower retinal arteries, higher LV mass, poorer diastolic and ventricular functions (all P ≤ 0.01), in EA and YA independent of traditional CVD risk factors. The composite ALS identified early-stress dysregulation in cardiometabolic health and higher odds for masked hypertension and prediabetes in young adults. Cumulative stress may be a modifiable, independent cardiometabolic risk factor in younger populations that needs further investigation.NEW & NOTEWORTHY This is the first study to assess the effect of stress, as a composite allostatic load score, on micro-, macrovascular, and central cardiac features in healthy emerging and young adults, independent of traditional cardiovascular risk markers. It exemplifies independent stress-induced changes throughout the cardiovascular tree, which may increase the risk of cardiometabolic complications, masked hypertension, and prediabetes. Sustained stress may be a key etiological factor in cardiometabolic disease development in a young population.}, } @article {pmid39917359, year = {2025}, author = {Ahmadi Marzaleh, M and Bastani, P and Raeyat Mohtashami, A and Farhadi, P and Ghanbari, S and Ravangard, R}, title = {Predicting Factors Affecting the Behavior of Healthcare Employees in the Use of Personal Protective Equipment During Epidemics Based on Godin et al's Model: A Study in Iran.}, journal = {Health services insights}, volume = {18}, number = {}, pages = {11786329251316668}, pmid = {39917359}, issn = {1178-6329}, abstract = {BACKGROUND: Protecting healthcare employees and preventing infection transmission are paramount concerns during epidemics. Predicting healthcare employees' behavior regarding the use of personal protective equipment (PPE) and identifying the related effective factors can guide educational and administrative strategies and enable timely interventions during outbreaks. This study aimed to predict factors affecting the healthcare employees' behavior in the use of PPE at Shiraz University of Medical Sciences in Iran, based on Godin et al's model.

METHODS: This was a cross-sectional and descriptive-analytical study. After reviewing the related articles and interviewing the experts and based on the model of Godin et al. (2008), a questionnaire was developed, validated, and tested for reliability using face and content validity as well as Cronbach's alpha. Collected data were analyzed using SPSS v.21 and modeled by Structural Equation Modeling (SEM) via SPSS v.21 and Smart PLS v.3 software.

RESULTS: The questionnaire was valid (CVI = 86.42, CVR = 81.71) and reliable (α = .85). The model exhibited appropriate measurement, structural, and overall fit. Beliefs about consequences, social influences, habits/past behavior, role and identity, characteristics of employees, moral norms, and beliefs about capabilities indirectly and significantly influenced behavior (P < .001). Additionally, beliefs about capabilities (P < .001), habits/past behavior (P = .001), and intention (P = .001) directly and significantly influenced PPE use behavior during epidemics.

CONCLUSION: The results emphasized the necessity of targeted interventions based on the studied model constructs within healthcare organizations. By promoting positive beliefs about PPE effectiveness and encouraging appropriate intentions and behaviors, healthcare organizations can significantly improve employee's adherence to PPE use during pandemics.}, } @article {pmid39916983, year = {2024}, author = {González Bolívar, S and Ayoubi, R and Alende, C and Fothouhi, M and Shlaifer, I and McPherson, PS and Laflamme, C and , and , }, title = {A guide to selecting high-performing antibodies for VAPB (UniProt ID: O95292) for use in western blot, immunoprecipitation, and immunofluorescence.}, journal = {F1000Research}, volume = {13}, number = {}, pages = {1559}, pmid = {39916983}, issn = {2046-1402}, mesh = {Humans ; *Immunoprecipitation/methods ; *Blotting, Western/methods ; *Fluorescent Antibody Technique/methods ; *Antibodies/immunology ; *Vesicular Transport Proteins/immunology/genetics/metabolism ; }, abstract = {VAPB is an adaptor protein known for its role as an anchor for other proteins at the endoplasmic reticulum. A mutant form of VAPB has been linked to amyotrophic lateral sclerosis and the underlying mechanisms resulting from this defect are studied by researchers in this area to uncover its implication in the disease. Here we have characterized six VAPB commercial antibodies for western blot, immunoprecipitation, and immunofluorescence using a standardized experimental protocol based on comparing read-outs in knockout cell lines and isogenic parental controls. These studies are part of a larger, collaborative initiative seeking to address antibody reproducibility issues by characterizing commercially available antibodies for human proteins and publishing the results openly as a resource for the scientific community. While use of antibodies and protocols vary between laboratories, we encourage readers to use this report as a guide to select the most appropriate antibodies for their specific needs.}, } @article {pmid39916853, year = {2025}, author = {Rosina, M and Scaricamazza, S and Riggio, F and Fenili, G and Giannessi, F and Matteocci, A and Nesci, V and Salvatori, I and Angelini, DF and Aquilano, K and Chiurchiù, V and Lettieri Barbato, D and Mercuri, NB and Valle, C and Ferri, A}, title = {Brown Adipose Tissue undergoes pathological perturbations and shapes C2C12 myoblast homeostasis in the SOD1-G93A mouse model of Amyotrophic Lateral Sclerosis.}, journal = {Heliyon}, volume = {11}, number = {3}, pages = {e41801}, pmid = {39916853}, issn = {2405-8440}, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by the selective loss of motor neurons. The contribution of peripheral organs remains incompletely understood. We focused our attention on brown adipose tissue (BAT) and its secreted extracellular vesicles (EVs) given their role in regulating systemic energy balance. In this study, we employed a multi-omics approach, including RNA sequencing (GEO identifier GSE273052) and proteomics (ProteomeXchange identifier PXD054147), to investigate the alterations in BAT and its EVs in the SOD1-G93A mouse model of ALS. Our results revealed consistent changes in the proteomic and transcriptomic profiles of BAT from SOD1-G93A mice, highlighting alterations such as mitochondrial dysfunction and impaired differentiation capacity. Specifically, primary brown adipocytes (PBAs) from SOD1-G93A mice exhibited differentiation impairment, respiratory defects, and alterations in mitochondrial dynamics. Furthermore, the BAT-derived EVs from SOD1-G93A mice displayed distinct changes in size distribution and cargo content. In parallel, such EVs negatively impacted the differentiation and homeostasis of C2C12 murine myoblasts, as well as induced atrophy in C2C12-derived myotubes. These findings suggest that BAT undergoes pathological perturbations in ALS mouse model and could impact on skeletal muscle homeostasis through the secretion of dysfunctional EVs.}, } @article {pmid39916336, year = {2025}, author = {Calvi, F and Fortuna, A and Bello, L and Anglani, M and Cecchin, D and Sabbatini, D and Andrigo, C and Ferullo, M and Ruggero, S and Falda, M and Pegoraro, E and Sorarù, G}, title = {MEPs and MRI Motor Band Sign as Potential Complementary Markers of Upper Motor Neuron Involvement in Amyotrophic Lateral Sclerosis.}, journal = {European journal of neurology}, volume = {32}, number = {2}, pages = {e70055}, pmid = {39916336}, issn = {1468-1331}, support = {//EuroBiobank/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology/diagnosis/pathology/diagnostic imaging ; Male ; Female ; Middle Aged ; *Magnetic Resonance Imaging ; *Evoked Potentials, Motor/physiology ; Aged ; Retrospective Studies ; *Motor Neurons/pathology/physiology ; Adult ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is characterized by the degeneration of both upper and lower motor neurons (UMNs and LMNs). Recognizing the involvement of UMNs is challenging because of the absence of reliable biomarkers beyond clinical evaluation.

AIM: To identify a reliable marker of UMN damage in a cohort of patients with ALS referring to the Motor Neuron Disease Clinic of the University Hospital of Padova.

METHODS: We retrospectively evaluated the clinical records of 79 patients with ALS and compared the results of various investigations, including the motor-evoked potentials (MEPs), positron emission tomography-magnetic resonance imaging (MRI) and light neurofilaments (NfLs), with the degree of UMN clinical involvement, as assessed by the Penn Upper Motor Neuron Score (PUMNS).

RESULTS: MEPs, considering the central motor conduction time (CMCT) values in both the upper and lower limbs, showed a significant correlation with the relative PUMNS subscores (p = 0.01, ρ = 0.4; and p = 0.005, ρ = 0.45, respectively). Additionally, there was a positive correlation between NfLs and PUMNS values (p = 0.04, ρ = 0.33). The presence of the motor band sign on MRI was associated with higher PUMNS values. Receiver operating characteristic analysis revealed that PUMNS accurately predicted abnormalities in CMCT values (specificity 86%, sensitivity 62%) and the presence of the motor band sign (specificity 58%, sensitivity 80%).

INTERPRETATION: In our cohort of patients with ALS, CMCT values proved to be the most reliable test for assessing UMN involvement, albeit the presence of the motor band sign on MRI showed higher sensitivity.}, } @article {pmid39915090, year = {2025}, author = {Noh, MY and Kwon, MS and Oh, KW and Nahm, M and Park, J and Jin, HK and Bae, JS and Son, B and Kim, SH}, title = {miRNA-214 to predict progression and survival in ALS.}, journal = {Journal of neurology, neurosurgery, and psychiatry}, volume = {96}, number = {7}, pages = {716-720}, pmid = {39915090}, issn = {1468-330X}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/mortality/blood ; *MicroRNAs/blood ; Disease Progression ; Male ; Female ; Middle Aged ; Aged ; Biomarkers/blood ; Neurofilament Proteins/blood ; Prognosis ; Adaptor Proteins, Signal Transducing/genetics ; Cohort Studies ; Cytokines/cerebrospinal fluid ; Adult ; Microglia/metabolism ; }, abstract = {BACKGROUND: Reliable biomarkers are essential for predicting the progression speed and prognosis of patients with amyotrophic lateral sclerosis (ALS). We previously identified NCK-associated protein 1 (NCKAP1) as a critical factor in the defective phagocytosis observed in induced microglia-like cells (iMGs) from patients with rapidly progressive sporadic ALS. This study explored the roles of microRNA (miRNA)-214, which targets the NCKAP1 gene, in the progression of ALS.

METHODS: The discovery cohort (n=29) was used to identify miR-214 targeting NCKAP1 genes. The validation cohort (n=132) was used to determine the clinical usability of miR-214 for predicting disease progression speed and survival time.

RESULTS: In the discovery cohort, miR-214 levels were increased in plasma and iMGs from rapidly progressive ALS participants. This finding was validated in another cohort of 132 ALS participants and 30 age-matched healthy volunteers. Plasma miR-214 levels correlated with disease progression, severity and survival, distinguishing between rapidly progressive and slowly progressive ALS. In addition, miR-214 levels also correlated with plasma neurofilament light chain (NfL) and cerebrospinal fluid inflammatory cytokines, showing specific associations with increased NfL and monocyte chemoattractant protein 1 (MCP-1). Survival prediction accuracy improved when miR-214 levels were considered with NfL or MCP-1 levels.

CONCLUSIONS: Plasma miRNA-214 could serve as a novel biomarker for predicting the progression and prognosis of ALS.}, } @article {pmid39914774, year = {2025}, author = {Zamani, A and Walker, AK and Wright, DK}, title = {Glymphatic dysfunction and neurodegeneration in ALS: Longitudinal insights from rNLS8 TDP-43 mice.}, journal = {Neurobiology of disease}, volume = {206}, number = {}, pages = {106832}, doi = {10.1016/j.nbd.2025.106832}, pmid = {39914774}, issn = {1095-953X}, mesh = {Animals ; *Amyotrophic Lateral Sclerosis/metabolism/pathology/diagnostic imaging/genetics/physiopathology ; *Glymphatic System/metabolism/diagnostic imaging/pathology/physiopathology ; *DNA-Binding Proteins/genetics/metabolism ; Mice ; Mice, Transgenic ; Disease Models, Animal ; Magnetic Resonance Imaging ; Humans ; Male ; Aquaporin 4/metabolism ; *Brain/metabolism/pathology/diagnostic imaging ; }, abstract = {Dysfunctional Tar DNA binding protein-43 (TDP-43) is found in approximately 95 % of all people with amyotrophic lateral sclerosis (ALS). Recent evidence suggests that the glymphatic system, which clears the brain of waste proteins, is impaired in ALS and may contribute to the accumulation of TDP-43. This study extends this work to investigate how glymphatic function changes over time in the rNLS8 doxycycline (Dox)-dependent TDP-43 mouse model of ALS. Motor function, advanced MRI biomarkers of neurodegeneration, and cortical glymphatic pathway gene expression were assessed together with dynamic contrast-enhanced MRI (DCE-MRI) assessment of glymphatic function at 0-, 3-, 7-, and 21-days after removing mice from Dox feed to initiate cytoplasmic human TDP-43 expression. A trend toward increased glymphatic influx was observed at 3-days post-Dox, together with MRI evidence of brain changes that occurred in the absence of hind-limb clasping and motor impairment. Glymphatic flow is facilitated by aquaporin-4 (AQP4) water channels polarized to astrocytic end feet. We found that while glymphatic function normalized to control levels at 7-days post-Dox, AQP4 expression in the cortex was significantly decreased. After 3-weeks of human TDP-43 expression, glymphatic dysfunction, weight loss, neurodegeneration, motor impairments and astrogliosis were observed. Our findings highlight early glymphatic dysfunction in ALS, suggesting its potential as a therapeutic target.}, } @article {pmid39914266, year = {2025}, author = {Wei, D and Freydenzon, A and Guinebretiere, O and Zaidi, K and Yang, F and Ye, W and Hammar, N and Modig, K and Wray, NR and Feychting, M and Hamieh, N and Ventelou, B and Lekens, B and Gantzer, L and Durrleman, S and McRae, A and Couvy-Duchesne, B and Fang, F and Nedelec, T and , }, title = {Ten years preceding a diagnosis of neurodegenerative disease in Europe and Australia: medication use, health conditions, and biomarkers associated with Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis.}, journal = {EBioMedicine}, volume = {113}, number = {}, pages = {105585}, pmid = {39914266}, issn = {2352-3964}, mesh = {Humans ; *Biomarkers/blood ; Aged ; Male ; Female ; *Amyotrophic Lateral Sclerosis/epidemiology/diagnosis ; *Alzheimer Disease/epidemiology/diagnosis ; Europe/epidemiology ; *Parkinson Disease/epidemiology/diagnosis ; Australia/epidemiology ; Aged, 80 and over ; Case-Control Studies ; *Neurodegenerative Diseases/epidemiology/diagnosis ; Risk Factors ; }, abstract = {BACKGROUND: Many studies have investigated early predictors for Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). However, evidence is sparse regarding specific and common predictors for these diseases. We aimed to identify medication use, health conditions, and blood biomarkers that might be associated with the risk of AD, PD, and ALS ten years later.

METHODS: We conducted population-based nested case-control studies of AD, PD, and ALS using electronic medical records in Europe (France, the UK, and Sweden) and Australia. We retrieved data on medication use, diagnosed health conditions, and measured blood biomarkers from electronic medical records or biomedical cohorts. Conditional logistic regression models and meta-analysis were applied to assess the associations between these factors and the risk of receiving a diagnosis of AD, PD, or ALS.

FINDINGS: We included a total of 149,642 AD cases (mean age: 79.1-81.2 years), 252,696 PD cases (73.2-75.9 years), and 27,533 ALS cases (64.4-69.6 years). The prescription of psychoanaleptics and nasal preparations was consistently associated with an increased risk of AD, PD, and ALS 5-10 years later. Constipation and use of related medications were associated with an increased risk of AD and PD, while diabetes and use of antidiabetics were associated with a reduced risk of ALS. A higher level of triglycerides was associated with a lower risk of AD, whereas a higher level of Apolipoprotein B was associated with a lower risk of PD, 5-10 years later.

INTERPRETATION: Psychoanaleptics and nasal preparations may serve as common predictors for diagnosis of AD, PD, and ALS 5-10 years later. Conversely, the increased prevalence of constipation is specific to AD and PD, while the decreased prevalence of diabetes and use of antidiabetics is specific to ALS.

FUNDING: EU Joint Programme-Neurodegenerative Disease Research.}, } @article {pmid39914221, year = {2025}, author = {Gusain, S and Mishra, CB and Yadav, K and Sharma, M and Saluja, D and Tiwari, M}, title = {Development of carbazole-based molecules for inhibition of mutant hSOD1 protein aggregation in Amyotrophic Lateral Sclerosis.}, journal = {Bioorganic & medicinal chemistry}, volume = {120}, number = {}, pages = {118091}, doi = {10.1016/j.bmc.2025.118091}, pmid = {39914221}, issn = {1464-3391}, mesh = {*Carbazoles/chemistry/pharmacology/chemical synthesis ; *Amyotrophic Lateral Sclerosis/drug therapy/metabolism/pathology ; Humans ; *Superoxide Dismutase-1/metabolism/genetics/chemistry/antagonists & inhibitors ; *Protein Aggregates/drug effects ; Mutation ; Animals ; Apoptosis/drug effects ; Mice ; Molecular Structure ; Structure-Activity Relationship ; Dose-Response Relationship, Drug ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterised by the loss of upper and lower motor neurons. Cu/Zn superoxide dismutase (SOD1) is one of the genes associated with the familial form of the disease (fALS). The mechanism of neuron degeneration by SOD1 is not clear, it is hypothesised that there is a toxic gain of function in the protein which leads to the downstream effects. In the present study, carbazole-based molecules have been rationally designed and synthesised as potential inhibitors of mutant hSOD1 protein aggregation. SG-9 and SG-10 prevented the aggregation of all three purified mutant hSOD1 proteins. Transmission electron microscopy and dynamic light scattering experiments also revealed that co-incubation of SG-9 and SG-10 with mutant hSOD1 protein resulted in smaller and slender fibril forming. Molecules SG-9 and SG-10 did not display toxicity and prevented Neuro-2a cells expressing hSOD1 G85R protein from its associated cytotoxicity. SG-9 and SG-10 were also able to prevent the transfected cells from apoptosis and were also able to reduce ROS levels associated with hSOD1 G85R protein aggregation significantly. Therefore, novel carbazole derivatives SG-9 and SG-10 proved to be effective inhibitors of mutant hSOD1 protein aggregation and can be further utilised as lead molecules for the amelioration of mutant hSOD1 aggregation-associated ALS.}, } @article {pmid39913612, year = {2025}, author = {Thomas, EV and Han, C and Kim, WJ and Asress, S and Li, Y and Taylor, JA and Gearing, M and Fournier, CN and McEachin, ZT and Seyfried, NT and Glass, JD}, title = {ALS plasma biomarkers reveal neurofilament and pTau correlate with disease onset and progression.}, journal = {Annals of clinical and translational neurology}, volume = {12}, number = {4}, pages = {714-723}, pmid = {39913612}, issn = {2328-9503}, support = {P01 NS084974/NS/NINDS NIH HHS/United States ; 5P01NS084974/CL/CLC NIH HHS/United States ; //American Academy of Neurology/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/blood/diagnosis/genetics ; *tau Proteins/blood ; Biomarkers/blood ; *Neurofilament Proteins/blood ; Female ; Male ; Middle Aged ; Disease Progression ; Adult ; Aged ; Pilot Projects ; Phosphorylation ; C9orf72 Protein/genetics ; }, abstract = {OBJECTIVE: We performed a pilot screen to assess the utility of the NULISA™ (Nucleic-acid-Linked Immuno-Sandwich Assay) platform in the identification of amyotrophic lateral sclerosis (ALS) biomarkers.

METHODS: Plasma from 86 individuals (48 ALS, 18 asymptomatic C9orf72 repeat expansion carriers (AsymC9), and 20 healthy controls) was analyzed via a multiplexed NULISA™ assay that includes 120 neurodegeneration-associated proteins. Statistical analysis of NULISA™ results was performed to identify proteins differentially expressed in plasma and their correlation with disease-associated parameters.

RESULTS: ALS plasma showed elevation of the established biomarkers, neurofilament light chain (NEFL) and neurofilament heavy chain (NEFH). Compared to controls and AsymC9, microtubule-associated protein tau (MAPT), phosphorylated tau 181 (pTau181), phosphorylated tau 217 (pTau217), phosphorylated tau 231 (pTau231), and phosphorylated TDP-43 (pTDP-43) were elevated in ALS. NEFL levels positively correlated with pTau181, pTau217, pTau231, and pTDP-43. MAPT and pTDP-43 were also correlated with pTau181, pTau217 and pTau231. Elevated pTau was negatively correlated with survival and ALSFRS-R. Spinal onset ALS was associated with higher pTau181, pTau217, and pTau231.

INTERPRETATION: We confirm previous reports showing elevated pTau181 in ALS plasma and show elevation of other phosphorylated tau forms, pTau217 and pTau231, typically observed in Alzheimer's disease. We provide preliminary data showing the detection and elevation of pTDP-43-409/410 in a subset of ALS samples compared to healthy controls. Neurofilament and tau levels are highly correlated suggesting their elevation may reflect a common pathology and disease state. Total and phosphorylated tau are correlated with multiple disease measures, such as ALS duration, ALSFRS-R, and site of onset.}, } @article {pmid39910731, year = {2025}, author = {Singh, S and Khan, S and Khan, S and Ansari, O and Malhotra, N and Shukla, SK and Narang, J}, title = {Muscle Matters: Transforming Amyotrophic Lateral Sclerosis Diagnostics with Next-Gen Biosensors and Smart Detection.}, journal = {ACS chemical neuroscience}, volume = {16}, number = {4}, pages = {563-587}, doi = {10.1021/acschemneuro.4c00664}, pmid = {39910731}, issn = {1948-7193}, mesh = {*Amyotrophic Lateral Sclerosis/diagnosis/physiopathology/genetics ; Humans ; *Biosensing Techniques/methods ; Biomarkers ; Electromyography/methods ; Motor Neurons ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder that primarily targets the motor system, causing patients' speech and swallowing ability to rapidly deteriorate. Although ALS is usually classified into familial and sporadic forms, diagnosing it can be extremely difficult due to the absence of definitive biomarkers, often resulting in delays in diagnosis. Current diagnostic practices rely heavily on clinical assessments that indicate damage to both upper motor neurons (UMNs) and lower motor neurons (LMNs). This includes comprehensive physical examinations, electromyography (EMG) to assess neuromuscular function, and the exclusion of other similar conditions such as cervical spondylotic myelopathy, multifocal motor neuropathy, and Kennedy's disease through appropriate diagnostic procedures. The urgent need for specific biomarkers is critical for timely diagnosis and therapeutic advancements in ALS management. While many recent developments in research have not yet translated into direct patient benefits, the recognition of ALS as a complex disease is beginning to influence clinical practice significantly. Optimal management strategies emphasize on symptom control and improving the quality of life for patients within a holistic healthcare framework. This review provides a comprehensive overview of ALS, delving into its pathophysiology, clinical symptoms, and the latest advancements in detection methods that utilize traditional approaches, innovative biosensors, and smart diagnostic technologies. It discusses various treatment options available for ALS while exploring future developments that may enhance patient screening and improve clinical outcomes. By integrating assessments into the underlying mechanisms of the disease with cutting-edge diagnostic approaches, this review aims to contribute meaningfully to ongoing efforts to optimize ALS management and therapeutic strategies, ultimately improving patient care and outcomes.}, } @article {pmid39910638, year = {2025}, author = {Möhwald, LM and Maier, A and Grehl, T and Weyen, U and Weydt, P and Günther, R and Lingor, P and Göricke, B and Petri, S and Grosskreutz, J and Boentert, M and Cordts, I and Weishaupt, JH and Dorst, J and Münch, C and Meyer, T and Baum, P}, title = {Shared prognostic information in amyotrophic lateral sclerosis - systematic assessment of the patients' perception of neurofilament light chain and the ALS functional rating scale.}, journal = {Neurological research and practice}, volume = {7}, number = {1}, pages = {6}, pmid = {39910638}, issn = {2524-3489}, support = {Open Access Publishing Fund of Leipzig University ("Read & Publish" contract with Springer Nature)//Open Access Publishing Fund of Leipzig University ("Read & Publish" contract with Springer Nature)/ ; }, abstract = {BACKGROUND: In amyotrophic lateral sclerosis (ALS), neurofilament light chain (NfL) was introduced as a prognostic biomarker. More recently, NfL values can be shared on the patient's ALS app. Also, the ALS functional rating scale (ALSFRS-R) is an established patient-reported assessment of disease progression. The scale can be obtained during clinic visits or remotely. However, few systematic data are available on the patients' perception of prognostic information about NfL and ALSFRS-R and the remote sharing of these data.

METHODS: In a multicenter study, 149 ALS patients were assessed for their perception of shared information about NfL and ALSFRS-R using an investigator-designed survey and established questionnaires. The recommendation of NfL and ALSFRS-R to fellow patients was assessed using the Net Promoter Score (NPS). Burden by shared information was investigated in two distinct settings: (1) clinic information when receiving results on NfL and/or ALSFRS-R during clinic visits and (2) remote information about NfL values and self-rating of the ALSFRS-R via the ALS app. General anxiety was measured by the Fear of Progression Questionnaire - Short Form (FoP-Q-SF).

RESULTS: Information about NfL and ALSFRS-R, respectively (n = 149), were regarded as relevant for patients themselves (75.2% and 77.2%) and for research (98% and 96%). The NPS showed a high recommendation rate for NfL (+ 21) and ALSFRS-R (+ 26). Only a minority of patients perceived shared information about NfL as burdensome, with a lower burden in the clinic setting (n = 1, 4.2%) than in the remote setting (n = 8, 12%; p = 0.015). Remote digital assessment of the ALSFRS-R was well received, with a reported burden in 9.8% (n = 9) of the participants. The FoP-Q-SF revealed fear of progression in 40% of the respondents (n = 60).

CONCLUSIONS: This study underscored the relevance of information about NfL and ALSFRS-R from the patient's perspective. Furthermore, patients proved to appreciate the relevance of this data for ALS research. Sharing information about NfL or ALSFRS-R was rarely perceived as burdensome even in a remote setting using the ALS app. These findings pave the way for further development of the patient-centered approach to sharing prognostic information in ALS.}, } @article {pmid39910617, year = {2025}, author = {Mai, YD and Zhang, Q and Fung, CL and Leung, SO and Chong, CH}, title = {CD22 modulation alleviates amyloid β-induced neuroinflammation.}, journal = {Journal of neuroinflammation}, volume = {22}, number = {1}, pages = {32}, pmid = {39910617}, issn = {1742-2094}, mesh = {Animals ; *Amyloid beta-Peptides/toxicity ; Mice ; Mice, Transgenic ; *Neuroinflammatory Diseases/metabolism/chemically induced/drug therapy ; *Sialic Acid Binding Ig-like Lectin 2/metabolism/genetics ; Humans ; Microglia/metabolism/drug effects ; Mice, Inbred C57BL ; Male ; }, abstract = {Neuroinflammation is a crucial driver of multiple neurodegenerative diseases, including Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS) and Parkinson's disease (PD). Yet, therapeutic targets for neurodegenerative diseases based on neuroinflammation still warrant investigation. CD22 has been implicated in neuroinflammatory diseases, namely AD. Specifically, plasma soluble CD22 (sCD22) level is upregulated in patients with AD. Direct experimental evidence for the role of CD22 in neuroinflammation is needed, as is a better understanding of its impact on microglia activation and therapeutic potential. Here we reported that sCD22 promotes neuroinflammation both in vivo and in vitro. sCD22 activated microglia via both p38 and ERK1/2 signaling pathway for the secretion of TNFα, IL-6 and CCL3. Moreover, sCD22 activated microglia via sialic acid binding domain and 2,6 linked sialic acid glycan on sCD22. The pivotal therapeutic potential of targeting CD22 was demonstrated in Amyloid β (Aβ) induced-neuroinflammation in hCD22 transgenic mice. Suciraslimab improved working memory and resolved neuroinflammation in vivo. Further, membrane CD22 inhibited Amyloid β (Aβ) induced-NFκB signaling pathway and mechanistic study delineated that suciraslimab suppressed Aβ-induced IL-1β secretion in human microglia and PBMC. Suciraslimab also suppressed IL-12 and IL-23 secretion in human PBMC. Moreover, suciraslimab reduced the surface expression of α4 integrin on B cells. Intriguingly, we discovered that CD22 interact with Aβ and suciraslimab enhanced internalization of CD22-Aβ complex in microglia. Our data highlights the importance of sCD22 in driving neuroinflammation and the dual mechanism of targeting CD22 to resolve Aβ-induced inflammation and promote Aβ phagocytosis.}, } @article {pmid39910275, year = {2025}, author = {Peters, TL and Qiu, W and Yang, H and Huang, W and Hu, Y and Zou, Z and Ye, W}, title = {Associations of cachexia and frailty with amyotrophic lateral sclerosis.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {4437}, pmid = {39910275}, issn = {2045-2322}, support = {2024XH028//Postdoctoral Fund project of Fujian Medical University Union Hospital/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/epidemiology/complications/physiopathology/etiology ; *Cachexia/complications/epidemiology ; Male ; Female ; *Frailty/complications/physiopathology ; Middle Aged ; Aged ; Prospective Studies ; United Kingdom/epidemiology ; Risk Factors ; Body Mass Index ; Hand Strength ; }, abstract = {In the present study, we investigated the associations of cachexia (loss of muscle, weight and fat) and frailty (loss of weight and muscle) status with the risk of developing amyotrophic lateral sclerosis, because these specific terms are rarely used in this research area. In this prospective study, we extracted cachexia and frailty status from the UK Biobank cohort to study the associations of these conditions (as determined via international classification of disease-10 codes) with amyotrophic lateral sclerosis. There was a greater risk of developing amyotrophic lateral sclerosis among individuals with cachexia and frailty status after adjusting for age, sex, income (pounds), body mass index, UK Biobank centers and smoking status. Among individuals with frailty status: a grip strength of < 21 kg, a slow walking speed, and exhaustion (more than half the days or nearly every day) increase the risk of developing amyotrophic lateral sclerosis. We believe that studying cachexia and frailty status can be used to help define and treat amyotrophic lateral sclerosis.}, } @article {pmid39908935, year = {2025}, author = {Lu, T and Li, J and Xiao, E and Zhong, H and Deng, J and Ma, L and Ning, Z and Xiao, T}, title = {Assemblage of root-associated microbiome contributes to disparate performance of two rice genotypes under aluminum stress.}, journal = {Plant physiology and biochemistry : PPB}, volume = {220}, number = {}, pages = {109539}, doi = {10.1016/j.plaphy.2025.109539}, pmid = {39908935}, issn = {1873-2690}, mesh = {*Oryza/genetics/microbiology/drug effects/growth & development ; *Aluminum/toxicity ; *Plant Roots/microbiology/drug effects/genetics ; *Microbiota/drug effects/genetics ; Genotype ; *Stress, Physiological/drug effects/genetics ; Rhizosphere ; Soil Microbiology ; }, abstract = {Aluminum (Al) toxicity severely inhibits rice growth under acidic soils, posing a significant threat to food security. The assemblies of root-associated microbiomes throughout the lifecycle of rice are hypothesized to furnish a resilient reservoir of ecological functions for rice growth performance under Al stresses. However, the mechanisms that drive the assembly of root-associated microbiomes of rice are largely unknown. In this study, we chose two rice genotypes (including aluminum-tolerant (Al-T) and aluminum-sensitive (Al-S)) as model plants to investigate the microbial assemblage of root-associated microbiome and their potential roles on the plant growth performance under Al stress. The microbial community diversity (Shannon) and evenness (Chao1) in the endosphere of the Al-T genotype gradually decreased, converging towards levels observed in the Al-S genotype. In addition, the rhizosphere and endosphere microbiomes of Al-T genotype are primarily influenced by deterministic processes, while those of Al-S genotype are more influenced by stochastic processes. Compared to Al-S genotype, Al-T genotype exhibited higher complexity and stability in its rhizosphere and endosphere microbiomes, while the rhizoplane microbiome showed the opposite trend. In the rhizosphere microbiome of the Al-T genotype, we identified Gallionellales, Rhodobacterales, and Rhizobiales as keystone taxa. Their abundance was closely associated with microbial functions, including indole-3-acetic acid (IAA) synthesis, phosphorus solubilization, glutathione (GSH) metabolism, and 1-aminocyclopropane-1-carboxylate (ACC) metabolism. In the Al-S genotype, the keystone taxa included Actinomycetales and Burkholderiales. This study offers new insights into plant adaptation to abiotic stress and underscores the significance of the assemblage of root-associated microbiome in this process.}, } @article {pmid39908735, year = {2025}, author = {Ghannam, IAY and Hassan, RM and Abdel-Maksoud, MS}, title = {Peroxisome proliferator-activated receptors (PPARs) agonists as promising neurotherapeutics.}, journal = {Bioorganic chemistry}, volume = {156}, number = {}, pages = {108226}, doi = {10.1016/j.bioorg.2025.108226}, pmid = {39908735}, issn = {1090-2120}, mesh = {Humans ; *Peroxisome Proliferator-Activated Receptors/agonists/metabolism ; *Neurodegenerative Diseases/drug therapy ; Animals ; *Neuroprotective Agents/pharmacology/chemistry/chemical synthesis/therapeutic use ; Molecular Structure ; }, abstract = {Neurodegenerative disorders are characterized by a continuous neurons loss resulting in a wide range of pathogenesis affecting the motor impairment. Several strategies are outlined for therapeutics of synthetic and natural PPARs agonists in some neurological disorders; Parkinson's disease (PD), Alzheimer's disease (AD), Multiple sclerosis (MS), Amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD). The aim of this review is to provide a recent update of the previously reported studies, and reviews dealing with the medicinal chemistry of PPARs and their agonists, and to highlight the outstanding advances in the development of both synthetic compounds including; PPARα agonists (fibrates), PPARγ agonists (thiazolidindiones), and PPARβ/δ agonists either as sole or dual acting PPAR full or pan agonists, in addition to the natural phytochemicals; acids, cannabinoids, and flavonoids for their different neuroprotection effects in the previously mentioned neurodegenerative disorders (PD, AD, MS, ALS, and HD). Moreover, this review reports the diverse pre-clinical and clinical studies of PPARs agonists in the neurodegenerative diseases via cellular, and animal models and human.}, } @article {pmid39908264, year = {2025}, author = {Hobert, MA and Helle, N and Siebert, C and Eisenhauer, A and Gledhill, M and Maetzler, W}, title = {Exploiting the Fractionation of Stable Isotopes in Biochemical Processes for Medical Diagnosis: A Narrative Review.}, journal = {Aging and disease}, volume = {}, number = {}, pages = {}, doi = {10.14336/AD.2024.1577}, pmid = {39908264}, issn = {2152-5250}, abstract = {Analysis of isotope distributions plays a crucial role in medical diagnostics. While radioactive and radiogenic isotopes - those that undergo or result from radioactive decay - are widely used, stable isotopes are less commonly applied despite their significant diagnostic potential. For example, calcium isotope ratio analysis is already commercially utilized for calcium loss and the early diagnosis of osteoporosis. Additionally, analyses of iron, copper, and zinc isotope ratios have been explored in various conditions, including hemochromatosis, Wilson's disease, cancer, Alzheimer's disease, and amyotrophic lateral sclerosis. Altered isotope ratios in these diseases are thought to reflect pathophysiologically relevant processes, making them promising biomarkers. This review provides a comprehensive overview of the current and potential applications of stable isotope analysis in medicine.}, } @article {pmid39907297, year = {2024}, author = {Čižek Sajko, M and Suklan, J and Osmanović, D and Peterlin, B}, title = {Translational Research on Polygenic Risk Scores in Common Neurodegenerative Diseases - A Scoping Review Protocol.}, journal = {Acta medica academica}, volume = {53}, number = {3}, pages = {303-308}, pmid = {39907297}, issn = {1840-2879}, mesh = {Humans ; Alzheimer Disease/genetics/diagnosis ; Amyotrophic Lateral Sclerosis/genetics ; Genetic Predisposition to Disease ; *Genetic Risk Score ; *Multifactorial Inheritance ; Multiple Sclerosis/genetics ; *Neurodegenerative Diseases/genetics ; Parkinson Disease/genetics/diagnosis ; Research Design ; Risk Assessment ; Risk Factors ; Scoping Review as Topic ; *Translational Research, Biomedical ; }, abstract = {OBJECTIVE: The purpose of this protocol is to clearly describe the process for the scoping review we plan to conduct on the topic of polygenic risk scores (PRS) in common neurodegenerative diseases. We will present the review's objective, the strategy for evidence search, the data extraction and analysis procedure, and how the results will be presented.

METHODS: The inclusion criteria for the planned scoping review will focus on evidence sources that involve PRS applied to neurogenerative diseases such as Multiple sclerosis, Parkinson's disease, Alzheimer's disease, and Amyotrophic lateral sclerosis in any phase of translational research, from early development to clinical implementation. This includes its use in risk prediction, early diagnosis, prognosis, and treatment decision-making. The research questions were created based on the population, context, and concept framework. We will consider both peer-reviewed papers and grey literature published in English or German for inclusion. Two independent reviewers will search for information.

CONCLUISON: The findings from the scoping review will be presented descriptively and summarized according to the research questions to illustrate the current status of translational research on PRS in common neurodegenerative diseases.}, } @article {pmid39907139, year = {2025}, author = {Matera, AG}, title = {Chaperone dysfunction in motor neuron disease: new insights from studies of the SMN complex.}, journal = {Genetics}, volume = {229}, number = {3}, pages = {}, pmid = {39907139}, issn = {1943-2631}, support = {R35 GM136435/GM/NIGMS NIH HHS/United States ; //USA National Institutes of Health/ ; }, mesh = {Humans ; Muscular Atrophy, Spinal/genetics/metabolism ; Amyotrophic Lateral Sclerosis/genetics/metabolism ; *SMN Complex Proteins/metabolism/genetics ; *Molecular Chaperones/metabolism/genetics ; Animals ; *Motor Neuron Disease/genetics/metabolism ; Motor Neurons/metabolism ; }, abstract = {Spinal muscular atrophy and amyotrophic lateral sclerosis are devastating neurodegenerative diseases characterized by motor neuron loss. Although these 2 disorders have distinct genetic origins, recent studies suggest that they share common etiological mechanisms rooted in proteostatic dysfunction. At the heart of this emerging understanding is the survival motor neuron (SMN) complex.}, } @article {pmid39906330, year = {2024}, author = {Hruška, J and Bachmann, P and Odei, SA}, title = {Enhancing ALS disease management: exploring integrated user value through online communities evidence.}, journal = {Frontiers in neurology}, volume = {15}, number = {}, pages = {1393261}, pmid = {39906330}, issn = {1664-2295}, abstract = {INTRODUCTION: Assistive technologies (ATs) offer significant potential to improve the quality of life for individuals with Amyotrophic Lateral Sclerosis (ALS). This study explores the concept of integrated user value (IUV), focusing on five key aspects: quality, user experience, cost-effectiveness, safety, and accessibility. Understanding IUV is crucial for enhancing the development and deployment of ATs in ALS disease management.

METHODS: A systematic search approach was utilized to collect data from Facebook ALS support groups, comprising posts from individuals with ALS and their caregivers. Using a predefined set of keywords, 416 posts were analyzed. The posts were categorized based on the five aspects of IUV, and an in-depth content analysis was conducted to explore patterns, challenges, and experiences associated with AT usage.

RESULTS: The analysis revealed significant challenges across all aspects of IUV. Quality and user experience were interlinked, with users frequently citing inadequate designs and unmet customization needs. Cost-effectiveness was a key concern, with high costs and limited insurance coverage contributing to financial strain. Accessibility issues, including delays in acquiring devices and insufficient public facilities, further highlighted systemic challenges. Safety concerns emphasized the need for personalized and intuitive AT designs.

DISCUSSION: The findings underscore the importance of a holistic approach to AT development, integrating all five aspects of IUV. Recommendations include enhancing product quality, ensuring affordability, prioritizing user-centered design, and addressing accessibility gaps. Collaboration between AT designers, healthcare providers, and policymakers is essential to optimize AT value and improve the quality of life for individuals with ALS and their caregivers.}, } @article {pmid39905402, year = {2025}, author = {Li, J and Guo, S and Sun, Q and An, N and Lin, J and Fei, Q}, title = {Bioinformatics screening and clinical validation of CircRNA and related miRNA in male osteoporosis.}, journal = {BMC musculoskeletal disorders}, volume = {26}, number = {1}, pages = {117}, pmid = {39905402}, issn = {1471-2474}, mesh = {Humans ; Male ; *RNA, Circular/genetics/blood ; *Osteoporosis/genetics/blood/diagnosis ; *MicroRNAs/genetics/blood ; *Computational Biology/methods ; Gene Regulatory Networks ; Middle Aged ; Gene Expression Profiling ; Aged ; RNA, Messenger/genetics ; Biomarkers/blood ; }, abstract = {BACKGROUND: The pathogenesis of male osteoporosis (MOP) remains unclear, with the role of genetic factors attracting the attention of researchers. In the present study, we aimed to investigate critical circRNA biomarkers associated with male osteoporosis.

METHODS: RNA-sequencing was performed to investigate the circRNA expression profiles between 3 men with osteoporosis and 3 with normal mass density. Then, shared mRNAs between host genes acquired in this present study and mRNAs acquired in previous study were identified to screen vital circRNAs associated with male osteoporosis. PPI networks of shared mRNAs were constructed and the hub genes in the PPI networks were identified with CytoHubba, a plugin in Cytoscape software (3.10.1). Finally, a ceRNA network of four circRNAs derived from three hub genes was constructed. Validation experiments were performed on selected circRNAs and related miRNAs in this ceRNA network using peripheral blood clinical samples.

RESULTS: In total, 657 circRNAs were detected in male osteoporosis. The shared mRNAs were significantly enriched in the metabolic pathways, RNA transport, Ubiquitin mediated proteolysis and Amyotrophic lateral sclerosis. Then, three genes, including SETD2, ATM and XPO1, were identified as hub genes with four algorithms. Ultimately, the ceRNA network, involving 4 circRNAs, 40 miRNAs, and 592 mRNAs, was obtained. Using 35 clinical samples, three potential circRNAs and three miRNAs associated with male osteoporosis were selected for validation. It was ultimately found that three miRNAs were upregulated in MOP, while hsa-circ-9130, novel_circ_0014940 and hsa-circ-0054894 were upregulated, hsa-circ-2484 and novel_circ_0033084 were downregulated in patients with MOP.

CONCLUSION: We emphasized the roles of several significantly up- and down-regulated circRNAs and four circRNAs derived from three hub genes in male osteoporosis. Differences in expression were confirmed for three miRNAs and five circRNAs in the ceRNA network among patients with male osteoporosis.}, } @article {pmid39904421, year = {2025}, author = {Dragoni, F and Garofalo, M and Di Gerlando, R and Rizzo, B and Bordoni, M and Scarian, E and Viola, C and Bettoni, V and Fiamingo, G and Tornabene, D and Scanu, L and Pansarasa, O and Diamanti, L and Gagliardi, S}, title = {Whole transcriptome analysis of unmutated sporadic ALS patients' peripheral blood reveals phenotype-specific gene expression signature.}, journal = {Neurobiology of disease}, volume = {206}, number = {}, pages = {106823}, doi = {10.1016/j.nbd.2025.106823}, pmid = {39904421}, issn = {1095-953X}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/blood ; Male ; Female ; Middle Aged ; Phenotype ; Aged ; *Gene Expression Profiling/methods ; *Transcriptome ; Adult ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is an adult neurodegenerative disorder. According to clinical criteria, ALS patients can be classified into eight subgroups: classic, bulbar, pyramidal, pure lower motor neuron, flail arm, pure upper motor neuron, flail leg, and respiratory. There are no well-established molecular biomarkers for early diagnosis, prognosis, and progression monitoring of this fatal disease. Classification based on clinical phenotypes could be associated with peculiar gene expression patterns shaped during lifespan, allowing the identification of specific sporadic ALS (sALS) subtypes with less heterogeneous clinical and biological features. Our objective was to define a phenotype-specific transcriptomic signature of distinct ALS phenotypes, and lay the foundation for biomarkers development. We characterized 48 sALS patients by clinical and paraclinical parameters, and subdivided them in "Classic" (n = 12), "Bulbar" (n = 10), "Flail Arm" (n = 7), "Flail Leg" (n = 10) and "Pyramidal" (n = 9) phenotypes. RNAs extracted from patients' PBMCs and 19 controls were sequenced. Our analysis allowed the visualization of gene expression differential clusters between patients and controls. Interestingly, only one gene (Y3_RNA, a misc_RNA component of the Ro60 ribonucleoprotein involved in cellular response to interferon-alpha) was upregulated at different levels across all phenotypes, whereas other genes appeared phenotype-specific. The work proposed stress the innovative view of ALS as a multi-systemic disorder rather than a pure motor neuron-associated and 'neurocentric' pathology. The possibility to cluster ALS patients based on their molecular signature pave the way for future personalized clinical trials and early diagnosis.}, } @article {pmid39902643, year = {2025}, author = {Abad-Yang, N and Raguseo, F and Di Michele, L and Patani, R and Di Antonio, M}, title = {The potential of multimolecular G-quadruplex structures for targeted treatment of Amyotrophic Lateral Sclerosis.}, journal = {Expert opinion on therapeutic targets}, volume = {29}, number = {1-2}, pages = {1-4}, doi = {10.1080/14728222.2025.2463361}, pmid = {39902643}, issn = {1744-7631}, } @article {pmid39902522, year = {2025}, author = {Yu, WQ and Zhao, LX and Bian, Y and Zhang, PX and Jia, L and Zhao, DM and Fu, Y and Ye, F}, title = {Pharmacophore Recombination Design, Synthesis, and Bioactivity of Ester-Substituted Pyrazole Purine Derivatives as Herbicide Safeners.}, journal = {Journal of agricultural and food chemistry}, volume = {73}, number = {6}, pages = {3341-3352}, doi = {10.1021/acs.jafc.4c07027}, pmid = {39902522}, issn = {1520-5118}, mesh = {*Herbicides/chemistry/pharmacology/chemical synthesis ; *Pyrazoles/chemistry/pharmacology/chemical synthesis ; *Purines/chemistry/pharmacology/chemical synthesis ; Molecular Docking Simulation ; Drug Design ; Acetolactate Synthase/chemistry/antagonists & inhibitors/metabolism ; Triticum/drug effects ; Plant Proteins/chemistry/antagonists & inhibitors/metabolism ; Molecular Structure ; Structure-Activity Relationship ; Esters/chemistry ; Enzyme Inhibitors/chemistry/pharmacology/chemical synthesis ; Plant Weeds/drug effects ; Molecular Dynamics Simulation ; Sulfonylurea Compounds/chemistry ; Pharmacophore ; }, abstract = {Mesosulfuron-methyl, an acetolactate synthase (ALS) inhibitor primarily applied to wheat and rye, can injure or even kill wheat crops. Herbicide safeners can improve the herbicide resistance of crops without reducing the herbicidal effect on targeted weed species. Herein, we present a series of pyrazole purine derivatives with the primary structure of the natural product cytokinin and commercialized safener mefenpyridyl, designed using the pharmacophore recombination method. The title compounds were synthesized and characterized using infrared spectroscopy, [1]H and [13]C nuclear magnetic resonance spectroscopy, and high-resolution mass spectrometry. A bioactivity assay proved that most of the target compounds can reduce the wheat phytotoxicity of mesosulfuron-methyl. Measurements of chlorophyll and glutathione contents, along with other enzyme activity assays, confirmed that compounds I-15 and I-13 exhibit higher safety activities compared with the mefenpyr-diethyl safener. Molecular structure comparisons demonstrated that I-15 is more readily absorbed and disseminated through the crop than the commercialized safener mefenpyr-diethyl. Molecular docking models and molecular dynamics simulations elucidated the protective mechanism of safeners; specifically, compound I-15 competitively binds to the ALS active site with mesosulfuron-methyl. The current study reveals the potential of pyrazole purine derivatives in the future discovery of novel herbicide safeners.}, } @article {pmid39902127, year = {2024}, author = {Ma, J and Wang, H and Gui, Z and Yang, Y}, title = {Unveiling the role of SYNGR4 in breast cancer development: a novel target for immunotherapy.}, journal = {Frontiers in oncology}, volume = {14}, number = {}, pages = {1490073}, pmid = {39902127}, issn = {2234-943X}, abstract = {INTRODUCTION: SYNGR4 is considered to be one of the causative genes for amyotrophic lateral sclerosis, but its role in breast cancer development has not been revealed.

METHODS: The expression of SYNGR4 in a variety of malignancies including breast cancer was analyzed using Genotype Tissue Expression (GTEx) and the Cancer Genome Atlas (TCGA) databases and verified by specimens collected from our center. The effect of SYNGR4 on breast cancer prognosis was analyzed using bioinformatics and possible pathways by which this molecule affects breast cancer prognosis were explored. The effect of SYNGR4 on immune infiltration of breast cancer was analyzed using GSVA, and the effects of SYNGR4 on breast cancer proliferation, migration, and tumor-associated macrophage polarization in cancer foci were verified by cellular and animal experiments, respectively.

RESULTS: SYNGR4 is highly expressed in a variety of malignant tumors, including breast cancer, and affects the prognosis of breast cancer patients. This may be a volatile effect through Organelle fission, chromosome segregation, nuclear division, etc. SYNGR4 overexpression affects breast cancer proliferation, migration, and tumor immune infiltration, and promotes breast cancer tumor-associated macrophage polarization toward M2.

DISCUSSION: SYNGR4 overexpression can affect the prognosis of breast cancer patients by promoting M2 polarization of tumor-associated macrophages in breast cancer, and this molecule may be a novel target for breast cancer immunotherapy.}, } @article {pmid39901730, year = {2025}, author = {Wu, W and Wang, X and Xu, Y and Ma, C and Qian, X and Qiu, W}, title = {Neuropathological comorbidity, genetics and cognition in a Chinese community-based autopsy cohort.}, journal = {Brain : a journal of neurology}, volume = {148}, number = {7}, pages = {2481-2492}, pmid = {39901730}, issn = {1460-2156}, support = {2021-1-I2M-025//CAMS Innovation Fund for Medical Sciences (CIFMS)/ ; 2021ZD0201100//STI 2030-Major Project/ ; 3332023040//Fundamental Research Funds for the Central Universities/ ; }, mesh = {Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; Asian People/genetics ; Autopsy ; *Brain/pathology ; China/epidemiology ; *Cognition/physiology ; Cohort Studies ; Comorbidity ; *Neurodegenerative Diseases/genetics/pathology/epidemiology ; }, abstract = {Neurodegenerative comorbidities are common and critical, yet data specific to the Chinese population remains limited. In this study, we aimed to investigate the prevalence and associations of neuropathological changes and comorbidities and their correlation with genetics and cognition in a community-dwelling autopsy cohort in China. Datasets of 610 participants were obtained from the National Human Brain Bank for Development and Function at the Chinese Academy of Medical Sciences/Peking Union Medical College. Neuropathological changes analysed included: Alzheimer's disease neuropathological change (ADNC; n = 331); α-synucleinopathies (n = 124), including 120 Lewy body disease (LBD) and 4 multiple system atrophy; limbic-predominant age-related TDP-43 encephalopathy neuropathological changes (LATE-NC; n = 341); primary age-related tauopathy (PART; n = 231); argyrophilic grain disease (n = 107); age-related tau astrogliopathy (n = 144); cerebral amyloid angiopathy (n = 183); and hippocampal sclerosis (n = 46). Frontotemporal lobar degeneration, amyotrophic lateral sclerosis and amygdala-predominant LBD were rare. Descriptive statistics and logistic regression models were used to assess the neuropathological associations. Increased age at death was correlated with increased severity in ADNC, LBD and LATE-NC and with a higher number of comorbidities. APOE ε4 allele frequency in the present autopsy cohort was 13.63%. The presence of the APOE ε4 allele was linked to an advanced ADNC stage and increased comorbidities. The co-pathology prevalence varied by pathologies, with notable increases in specific subgroups: within the ADNC subgroups, LBD, LATE-NC, cerebral amyloid angiopathy and hippocampal sclerosis were more frequent in advanced stages; in the LATE-NC subgroups, ADNC, cerebral amyloid angiopathy and age-related tau astrogliopathy increased, and PART decreased in higher LATE-NC stages. PART cases presented the highest proportion of pure pathology (37.2%) compared with the other groups. Advanced ADNC stages were significantly associated with higher LATE-NC stages, and vice versa. Neocortical LBD was correlated with elevated ADNC levels, and higher LATE-NC stages were associated with worsening LBD pathology. High-level ADNC, neocortical LBD and stage 3 of LATE-NC were identified as independent predictors of severe cognition status. Our study suggests that older age at death and APOE ε4 presence are the risk factors for neuropathological comorbidities in Chinese people. The findings underscore the importance of considering comorbid neurological diagnoses and therapies in clinical practice.}, } @article {pmid39901566, year = {2025}, author = {Park, NY and Heo, Y and Yang, JW and Yoo, JM and Jang, HJ and Jo, JH and Park, SJ and Lin, Y and Choi, J and Jeon, H and Cha, SJ and Bae, G and Kim, D and Kim, J and Zeno, W and Park, JB and Isozumi, N and Saio, T and Kim, SH and Lee, H and Hong, BH and Nahm, M and Lee, YH and Hong, YB}, title = {Graphene Quantum Dots Attenuate TDP-43 Proteinopathy in Amyotrophic Lateral Sclerosis.}, journal = {ACS nano}, volume = {19}, number = {9}, pages = {8692-8710}, pmid = {39901566}, issn = {1936-086X}, mesh = {*Amyotrophic Lateral Sclerosis/metabolism/drug therapy/pathology ; *Graphite/chemistry/pharmacology ; Animals ; *DNA-Binding Proteins/metabolism/genetics/chemistry ; Humans ; Mice ; *Quantum Dots/chemistry ; Mice, Transgenic ; Disease Models, Animal ; *TDP-43 Proteinopathies/drug therapy/metabolism ; Motor Neurons/metabolism/drug effects ; }, abstract = {Aberrant phase separation- and stress granule (SG)-mediated cytosolic aggregation of TDP-43 in motor neurons is the hallmark of amyotrophic lateral sclerosis (ALS). In this study, we found that graphene quantum dots (GQDs) potentially modulate TDP-43 aggregation during SG dynamics and phase separation. The intrinsically disordered region in the C-terminus of TDP-43 exhibited amyloid fibril formation; however, GQDs inhibited the formation of amyloid fibrils through direct intermolecular interactions with TDP-43. These effects were accompanied by attenuation of the ALS phenotype in animal models. Additionally, GQDs delayed the onset and survival of TDP-43 transgenic mouse models by enhancing motor neuron survival, reducing glial activation, and reducing the cytosolic aggregation of TDP-43 in motor neurons. In this research, we demonstrated the efficacy of GQDs on the SG-mediated aggregation of TDP-43 and the binding property of GQDs with TDP-43. Additionally, we demonstrated the clinical feasibility of GQDs using several animal models and other types of ALS caused by FUS and C9orf72. Therefore, GQDs could offer a new therapeutic approach for proteinopathy-associated ALS.}, } @article {pmid39901378, year = {2025}, author = {San Gil, R and Walker, AK}, title = {Unlocking Disease-Modifying Treatments for TDP-43-Mediated Neurodegeneration.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {47}, number = {4}, pages = {e202400257}, pmid = {39901378}, issn = {1521-1878}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism/pathology/genetics/therapy ; *DNA-Binding Proteins/metabolism/genetics ; *Frontotemporal Dementia/metabolism/pathology/genetics/therapy ; Animals ; *Neurodegenerative Diseases/metabolism ; }, abstract = {Neurons degenerate in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), causing progressive and inevitably fatal neurological decline. The best therapeutic strategies target underlying disease mediators, but after decades of intensive research, the causes of these neurodegenerative diseases remain elusive. Recently, coordinated activities of large consortia, increasing open access to large datasets, new methods such as cryo-transmission electron microscopy, and advancements in high-resolution omics technologies have offered new insights into the biology of disease that bring us closer to understanding mechanisms of neurodegeneration. In particular, improved understanding of the roles of the key pathological protein TAR DNA binding protein 43 (TDP-43) in disease has revealed intriguing new opportunities that provide hope for better diagnostic tools and effective treatments for ALS and FTD.}, } @article {pmid39900510, year = {2025}, author = {van Altena, EJE and Jansen, BHE and Vis, AN}, title = {Reply to Ignacio Puche-Sanz, Ugo Giovanni Falagario, Giorgio Gandaglia, et al's Letter to the Editor re: Evelien J.E. van Altena, Bernard H.E. Jansen, Marieke L. Korbee, et al. Prostate-specific Membrane Antigen Positron Emission Tomography Before Reaching the Phoenix Criteria for Biochemical Recurrence of Prostate Cancer After Radiotherapy: Earlier Detection of Recurrences. Eur Urol Oncol. In press. https://doi.org/10.1016/j.euo.2024.09.015.}, journal = {European urology oncology}, volume = {8}, number = {3}, pages = {854-855}, doi = {10.1016/j.euo.2025.01.011}, pmid = {39900510}, issn = {2588-9311}, } @article {pmid39899435, year = {2025}, author = {Blake, J and Peryer, G and Dance, R and Parke, S and Aryankhesal, A and Farquhar, M}, title = {How can healthcare professionals work with families to address misaligned expectations of recovery in brain injury rehabilitation? A scoping review.}, journal = {Brain injury}, volume = {39}, number = {7}, pages = {551-564}, doi = {10.1080/02699052.2025.2450603}, pmid = {39899435}, issn = {1362-301X}, mesh = {Humans ; *Brain Injuries/rehabilitation/psychology ; *Health Personnel/psychology ; *Family/psychology ; *Professional-Family Relations ; Recovery of Function ; }, abstract = {INTRODUCTION: Most survivors of severe acquired brain injuries will have significant long-term disability. During inpatient rehabilitation, families often have expectations of recovery that do not match healthcare professional opinion. This impacts on patient care, service processes, professional-family relations, and wellbeing. This review aimed to understand how family expectations are managed in this setting, and to explore potential areas of improvement.

METHOD: A scoping review was conducted by searching CINAHL, Medline, EMBASE and Web of Science. Krieger et al's 'Conceptual Building Blocks' provided a framework to analyze the data using a 'best fit' framework synthesis approach.

RESULTS: Twenty-one papers were included in the review. Six sub-themes within three overarching themes were generated, which explored recommendations for effective expectation management. The sub-themes within the 'staff behaviors' theme were 'appropriate information provision,' 'open communication' and 'prioritize family.' Sub-themes within 'system behaviors' were 'cultural change' and 'increased resource.' 'Rehabilitation as a shared process' was the third theme.

DISCUSSION: Misaligned expectations of recovery appear to reflect a range of unmet family needs related to their position within the healthcare hierarchy, professional-family communication, and their involvement in rehabilitation processes. Early identification of family and healthcare professional expectations alongside regular review may prevent misunderstanding and conflict.}, } @article {pmid39898446, year = {2025}, author = {Boddy, SL and Simpson, RM and Walters, SJ and Bamford, H and Walsh, T and McDermott, CJ and , }, title = {Estimating the minimum important difference in the ALSFRS-R-instrument in people living with MND.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {26}, number = {3-4}, pages = {249-258}, pmid = {39898446}, issn = {2167-9223}, support = {MCRGS-07-16-13/MCCC_/Marie Curie/United Kingdom ; }, mesh = {Humans ; Male ; Female ; Middle Aged ; Aged ; Longitudinal Studies ; *Amyotrophic Lateral Sclerosis/diagnosis/psychology ; *Quality of Life/psychology ; Severity of Illness Index ; *Minimal Clinically Important Difference ; Adult ; }, abstract = {Objective: The Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) is a commonly used outcome measure in clinical trials for motor neuron disease (MND) therapies. As such, understanding how differences in scores relate to patient perception of their disease status is important when interpreting ALSFRS-R data. Our study sought to estimate the minimal important difference (MID) for the ALSFRS-R, the smallest difference in scores at which patients perceive a change in their quality of life. Methods: Data were collected as part of a longitudinal, observational saliva management study, ProSec3. These included both the ALSFRS-R and a global rating of change question (GRoC), which asked participants to rate how their disease had progressed since the previous visit. Anchor-based and distribution-based methods have been used to estimate the MID of the ALSFRS-R. The MID was estimated using two methods of calculating the total ALSFRS-R score, the original summation scale method and the recently proposed interval scale method. Results: A total of 145 people with MND had longitudinal ALSFRS-R and GRoC data. Different methods estimated the ALSFRS-R MID to be in the range of 2.02-5.43 for the summation scale and 1.23-3.31 for the interval scale method over a 3-month period, the time between study visits. Using anchor-based methods our MID estimates for the ALSFRS-R are 3.8 points and 2 points, respectively. Conclusions: The results of this study can guide clinicians and researchers in the interpretation of ALSFRS-R data. However, further studies are required to more precisely estimate the ALSFRS-R MID.}, } @article {pmid39897942, year = {2025}, author = {Quarracino, C and Capani, F and Otero-Losada, M and Rodríguez, GE and Pérez-Lloret, S}, title = {Frequency of orthostatic hypotension in the Pooled Resource Open-Access ALS Clinical Trials database.}, journal = {Frontiers in neurology}, volume = {16}, number = {}, pages = {1512357}, pmid = {39897942}, issn = {1664-2295}, abstract = {PURPOSE: To explore the frequency of orthostatic hypotension (OH) in a large sample of amyotrophic lateral sclerosis patients (ALS).

METHODS: From the PRO-ACT database, data of 1,240 ALS patients were analyzed, focusing on blood pressure and heart rate before and after standing. OH was defined as a drop in systolic/diastolic blood pressure > 20/10 mm Hg within 3 min of standing. Neurogenic OH was diagnosed when the heart rate increase was below 15 bpm in patients not taking medications that could affect this response.

RESULTS: At baseline, 138 (11.1%) patients showed OH, 76.1% of whom had neurogenic OH. At follow-up, 163 patients (13.1%) had OH, 71.2% with neurogenic OH. Only 22.5% of the patients with OH at baseline had OH at follow-up.

CONCLUSION: In a large sample of ALS patients, OH occurred in 11-13%, pointing to a subgroup that might require special care to avoid related complications.}, } @article {pmid39897290, year = {2025}, author = {McBenedict, B and Hauwanga, WN and Nezam, U and Ko Oo, A and Eapi, S and Pradhan, S and Dang, NB and Cher, PW and Orsini, MA and Lima Pessôa, B}, title = {Amyotrophic Lateral Sclerosis (ALS) Type 8: A Narrative Review.}, journal = {Cureus}, volume = {17}, number = {1}, pages = {e76717}, pmid = {39897290}, issn = {2168-8184}, abstract = {Amyotrophic lateral sclerosis type 8 (ALS8) is a rare familial subtype of ALS caused by mutations in the vesicle-associated membrane protein-associated protein B (VAPB) gene, particularly the p.P56S mutation. It is distinguished by slower disease progression and an earlier onset compared to sporadic ALS forms, along with unique clinical features such as severe cramping, fasciculations, postural tremors, and cognitive and behavioral impairments. Although current pharmacological options, such as riluzole, edaravone, and sodium phenylbutyrate/taurursodiol, provide modest benefits, they fail to address the underlying genetic mechanisms of ALS8. Emerging gene therapies, RNA-based interventions, and stem cell approaches hold promise for precision-targeted treatments but face challenges in clinical application. Symptom management strategies, including respiratory, nutritional, and psychological support, are crucial for improving patient outcomes and quality of life. Despite significant progress in understanding the genetic and molecular pathogenesis of ALS8, its rarity, phenotypic variability, and limited clinical data pose challenges to therapeutic advancements. This narrative review highlights current therapeutic strategies, the unique clinical trajectory of ALS8, and potential pathways for innovative, subtype-specific interventions, emphasizing the need for multidisciplinary and targeted approaches to optimize care for this distinct ALS subtype.}, } @article {pmid39896335, year = {2025}, author = {Eckardt, A and Marble, C and Fern, B and Moritz, H and Kotula, C and Ke, J and Rebancos, C and Robertson, S and Nishimune, H and Suzuki, M}, title = {Muscle-specific Bet1L knockdown induces neuromuscular denervation, motor neuron degeneration, and motor dysfunction in a rat model of familial ALS.}, journal = {Frontiers in neuroscience}, volume = {19}, number = {}, pages = {1527181}, pmid = {39896335}, issn = {1662-4548}, support = {R01 AR077191/AR/NIAMS NIH HHS/United States ; R01 NS091540/NS/NINDS NIH HHS/United States ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a neuromuscular disease characterized by specific loss of motor neurons in the spinal cord and brain stem. Although ALS has historically been characterized as a motor neuron disease, there is evidence that motor neurons degenerate in a retrograde manner, beginning in the periphery at the neuromuscular junctions (NMJs) and skeletal muscle. We recently reported a vesicle trafficking protein Bet1L (Bet1 Golgi Vesicular Membrane Trafficking Protein Like) as a new molecule possibly linked to NMJ degeneration in ALS. In this study, we tested the hypothesis that Bet1L gene silencing in skeletal muscle could influence NMJ integrity, motor neuron function, and survival in a rat model of familial ALS (SOD1[G93A] transgenic). Small interfering RNA (siRNA) targeting the Bet1L gene was injected on a weekly basis into the hindlimb muscle of pre-symptomatic ALS and wild-type (WT) rats. After 3 weeks, intramuscular Bet1L siRNA injection significantly increased the number of denervated NMJs in the injected muscle. Bet1L knockdown decreased motor neuron size in the lumbar spinal cord, which innervated the siRNA-injected hindlimb. Impaired motor function was identified in the hindlimbs of Bet1L siRNA-injected rats. Notably, the effects of Bet1L knockdown on NMJ and motor neuron degeneration were more significant in ALS rats when compared to WT rats. Together, Bet1L knockdown induces denervation of NMJs, but also this knockdown accelerates the disease progression in ALS. Our results provide new evidence to support the potential roles of Bet1L as a key molecule in NMJ maintenance and ALS pathogenesis.}, } @article {pmid39894843, year = {2025}, author = {Chen, L and Shen, Q and Liu, Y and Zhang, Y and Sun, L and Ma, X and Song, N and Xie, J}, title = {Homeostasis and metabolism of iron and other metal ions in neurodegenerative diseases.}, journal = {Signal transduction and targeted therapy}, volume = {10}, number = {1}, pages = {31}, pmid = {39894843}, issn = {2059-3635}, support = {32471049//National Natural Science Foundation of China (National Science Foundation of China)/ ; 32170984//National Natural Science Foundation of China (National Science Foundation of China)/ ; 32200802//National Natural Science Foundation of China (National Science Foundation of China)/ ; ZR2020YQ23//Natural Science Foundation of Shandong Province (Shandong Provincial Natural Science Foundation)/ ; ZR2024MC153//Natural Science Foundation of Shandong Province (Shandong Provincial Natural Science Foundation)/ ; }, mesh = {Humans ; *Iron/metabolism ; *Neurodegenerative Diseases/metabolism/drug therapy/pathology/genetics ; *Homeostasis ; Zinc/metabolism ; Copper/metabolism ; Animals ; Parkinson Disease/metabolism/genetics/drug therapy/pathology ; Alzheimer Disease/metabolism/genetics/drug therapy/pathology ; Manganese/metabolism ; Oxidative Stress ; Chelating Agents/therapeutic use ; }, abstract = {As essential micronutrients, metal ions such as iron, manganese, copper, and zinc, are required for a wide range of physiological processes in the brain. However, an imbalance in metal ions, whether excessive or insufficient, is detrimental and can contribute to neuronal death through oxidative stress, ferroptosis, cuproptosis, cell senescence, or neuroinflammation. These processes have been found to be involved in the pathological mechanisms of neurodegenerative diseases. In this review, the research history and milestone events of studying metal ions, including iron, manganese, copper, and zinc in neurodegenerative diseases such as Parkinson's disease (PD), Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD), will be introduced. Then, the upstream regulators, downstream effector, and crosstalk of mental ions under both physiologic and pathologic conditions will be summarized. Finally, the therapeutic effects of metal ion chelators, such as clioquinol, quercetin, curcumin, coumarin, and their derivatives for the treatment of neurodegenerative diseases will be discussed. Additionally, the promising results and limitations observed in clinical trials of these metal ion chelators will also be addressed. This review will not only provide a comprehensive understanding of the role of metal ions in disease development but also offer perspectives on their modulation for the prevention or treatment of neurodegenerative diseases.}, } @article {pmid39894561, year = {2025}, author = {Ito, T and Ohuchi, K and Kurita, H and Murakami, T and Takizawa, S and Fujimaki, A and Murata, J and Oida, Y and Hozumi, I and Kitaichi, K and Inden, M}, title = {Activated Fibroblast Growth Factor Receptor 1 Mitigated Poly-PR-Induced Oxidative Stress and Protein Translational Impairment.}, journal = {Biological & pharmaceutical bulletin}, volume = {48}, number = {2}, pages = {93-100}, doi = {10.1248/bpb.b24-00794}, pmid = {39894561}, issn = {1347-5215}, mesh = {*Oxidative Stress/drug effects ; Animals ; *Receptor, Fibroblast Growth Factor, Type 1/metabolism/genetics ; NF-E2-Related Factor 2/metabolism/genetics ; Mice ; Protein Biosynthesis/drug effects ; Cell Line ; Motor Neurons/metabolism/drug effects ; Amyotrophic Lateral Sclerosis/metabolism/genetics ; Humans ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by selective motor neuron cell death. A GGGGCC hexanucleotide repeat expansion (HRE) within the chromosome 9 open reading frame 72 (C9orf72) gene is a major causative factor in ALS. This abnormal HRE triggers five types of dipeptide repeat protein (DPR), each composed of two alternating amino acid expressions. Among the DPRs, arginine-rich Poly-PR localizes predominantly to the nucleus, exerting particularly strong toxicity on motor and cortical neurons. Several mechanisms have been proposed for poly-PR-induced neurotoxicity. In this study, poly-PR-expressing NSC34 motor neuron-like cells showed an increase in oxidative stress. Fibroblast growth factor receptor 1 (FGFR1) is known to promote neurogenesis and inhibit apoptosis in neurons. However, its neuroprotective effects against DPR-induced toxicity have not been previously reported. Here, we demonstrated that FGFR1 activation reduced oxidative stress by upregulating nuclear factor erythroid 2-related factor 2 (NRF2) expression. Furthermore, we propose that the increase in NRF2 through FGFR1 activation may result from the alleviation of protein translation impairment. Overall, these findings suggest that FGFR1 activation provides neuroprotection against poly-PR toxicity and may represent a potential therapeutic strategy for ALS.}, } @article {pmid39894369, year = {2025}, author = {Jairath, N and Manduca, S and Que, SKT}, title = {Response to Wang et al's limitations and risks of custom GPTs in dermatology. Comment on "ReconGPT: A novel artificial intelligence tool and its potential use in post-Mohs reconstructive decision-making".}, journal = {Journal of the American Academy of Dermatology}, volume = {92}, number = {5}, pages = {e163}, doi = {10.1016/j.jaad.2025.01.072}, pmid = {39894369}, issn = {1097-6787}, } @article {pmid39893487, year = {2025}, author = {Pilotto, F and Smeele, PH and Scheidegger, O and Diab, R and Schobesberger, M and Sierra-Delgado, JA and Saxena, S}, title = {Kaempferol enhances ER-mitochondria coupling and protects motor neurons from mitochondrial dysfunction and ER stress in C9ORF72-ALS.}, journal = {Acta neuropathologica communications}, volume = {13}, number = {1}, pages = {21}, pmid = {39893487}, issn = {2051-5960}, support = {725825//European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program/ ; }, mesh = {Animals ; *Endoplasmic Reticulum Stress/drug effects/physiology ; *Kaempferols/pharmacology/therapeutic use ; *Amyotrophic Lateral Sclerosis/pathology/genetics/drug therapy/metabolism ; *Mitochondria/drug effects/metabolism/pathology ; Humans ; C9orf72 Protein/genetics/metabolism ; *Motor Neurons/drug effects/metabolism/pathology ; *Neuroprotective Agents/pharmacology ; Mice ; *Endoplasmic Reticulum/drug effects/metabolism ; Mice, Transgenic ; Disease Models, Animal ; Male ; Mice, Inbred C57BL ; Rats ; }, abstract = {Repeat expansions in the C9ORF72 gene are a frequent cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. Considerable progress has been made in identifying C9ORF72-mediated disease and resolving its underlying etiopathogenesis. The contributions of intrinsic mitochondrial deficits as well as chronic endoplasmic reticulum stress to the development of the C9ORF72-linked pathology are well established. Nevertheless, to date, no cure or effective therapy is available, and thus attempts to find a potential drug target, have received increasing attention. Here, we investigated the mode of action and therapeutic effect of a naturally occurring dietary flavanol, kaempferol in preclinical rodent and human models of C9ORF72-ALS. Notably, kaempferol treatment of C9ORF72-ALS human patient-derived motor neurons/neurons, resolved mitochondrial deficits, promoted resiliency against severe ER stress, and conferred neuroprotection. Treatment of symptomatic C9ORF72 mice with kaempferol, normalized mitochondrial calcium uptake, restored mitochondria function, and diminished ER stress. Importantly, in vivo, chronic kaempferol administration ameliorated pathological motor dysfunction and inhibited motor neuron degeneration, highlighting the translational potential of kaempferol. Lastly, in silico modelling identified a novel kaempferol target and mechanistically the neuroprotective mechanism of kaempferol is through the iP3R-VDAC1 pathway via the modulation of GRP75 expression. Thus, kaempferol holds great promise for treating neurodegenerative diseases where both mitochondrial and ER dysfunction are causally linked to the pathophysiology.}, } @article {pmid39893047, year = {2025}, author = {Zhu, A and Hu, JC}, title = {Reply to Alireza Ghoreifi, Jaffar Hussain, Wei Phin Tan, et al's Letter to the Editor re: Alec Zhu, Mary O. Strasser, Timothy D. McClure, et al. Comparative Effectiveness of Partial Gland Cryoablation Versus Robotic Radical Prostatectomy for Cancer Control. Eur Urol Focus 2024;10:843-50.}, journal = {European urology focus}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.euf.2025.01.013}, pmid = {39893047}, issn = {2405-4569}, } @article {pmid39891470, year = {2025}, author = {Iazzolino, B and Palumbo, F and Moglia, C and Manera, U and Grassano, M and Matteoni, E and Cabras, S and Brunetti, M and Vasta, R and Pagani, M and Mora, G and Canosa, A and Calvo, A and Chiò, A}, title = {Frequency and Early Predictors of Cognitive Deterioration in Amyotrophic Lateral Sclerosis: A Longitudinal Population-Based Study.}, journal = {Annals of neurology}, volume = {97}, number = {6}, pages = {1122-1133}, pmid = {39891470}, issn = {1531-8249}, support = {ALS-Care//EU Joint Programme - Neurodegenerative Disease Research/ ; Brain-Mend//EU Joint Programme - Neurodegenerative Disease Research/ ; 101017598//HORIZON EUROPE Health/ ; RF-2016-02362405//Ministero della Salute/ ; 2017SNW5MB//Ministero dell'Università e della Ricerca (Department of Excellence)/ ; 20228N7573//Ministero dell'Università e della Ricerca (Department of Excellence)/ ; 259867//FP7 Health/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnostic imaging/complications/genetics/psychology ; Male ; Female ; Middle Aged ; Aged ; Longitudinal Studies ; Disease Progression ; *Cognitive Dysfunction/etiology/diagnostic imaging/epidemiology ; Neuropsychological Tests ; Positron-Emission Tomography ; Adult ; }, abstract = {OBJECTIVE: The objective is to evaluate cognitive and behavioral progression and identify early predictors of these changes in a cohort of amyotrophic lateral sclerosis (ALS) patients.

METHODS: A total of 161 ALS patients were tested at diagnosis (T0), and 107 were re-tested after 1 year (T1) using cognitive/behavioral tests. All patients underwent whole-genome sequencing, and 46 patients (ALS-normal cognition [CN]) underwent [18F]Fluorodeoxyglucose positron emission tomography.

RESULTS: Of the 161 patients, 107 were re-rested at T1; non-retested patients included 10 with frontotemporal dementia and 44 who were either non-testable or deceased. At T0, 67 patients (62.6%) were classified as ALS-CN, whereas 40 (38.4%) showed some degree of cognitive/behavioral impairment. Eighteen ALS-CN patients (26.9%) experienced cognitive decline at T1. Phenoconverters had lower baseline scores in letter fluency (Letter Fluency Test [FAS]) (p < 0.001), Edinburgh Cognitive and Behavioral ALS Screen (ECAS) verbal fluency score (p = 0.017). Both tests were independently predictive of phenoconversion in binary logistic regression models, with optimal cut-off scores of 28.75 and 14.2, with good sensitivity and specificity. Other predictors included older age, lower education, and ALS-related genetic variants. Phenoconverters were hypometabolic in the left temporal lobe. Thirteen (32.5%) of the 40 patients with cognitive impairment at T0 worsened by T1, with FAS (p = 0.02) and the ECAS verbal fluency score (p = 0.023) predicting further decline.

INTERPRETATION: Approximately 30% of ALS patients experienced cognitive/behavioral decline within the first year after diagnosis. FAS and ECAS verbal fluency were predictive of cognitive phenoconversion. Our findings highlight the importance of early detection of at-risk individuals and the need for longitudinal cognitive assessments to monitor disease progression. ANN NEUROL 2025;97:1122-1133.}, } @article {pmid39891383, year = {2025}, author = {Chen, M and Cui, H and Zhang, X and Ma, S and Guo, J and Liu, Z and Gu, D and Fan, Y}, title = {Super-Enhancer Protects Cells From Toxicity of C9orf72 Poly(proline-arginine) by Inducing the Expression of KPNA2/KPNB1.}, journal = {Cell biochemistry and function}, volume = {43}, number = {2}, pages = {e70053}, doi = {10.1002/cbf.70053}, pmid = {39891383}, issn = {1099-0844}, support = {//This work was supported by the National Natural Science Foundation of China (31970616, 82070505) and Jiangsu Provincial Natural Science Foundation (BK20211330)./ ; }, mesh = {Humans ; *alpha Karyopherins/genetics/metabolism ; *C9orf72 Protein/metabolism/genetics ; Cell Nucleus/metabolism ; Triazoles/pharmacology ; Cell Death/drug effects ; Azepines ; }, abstract = {Hexanucleotide repeat expansions in C9orf72 are the most common genetic mutation associated with amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) (C9-ALS/FTD). Dipeptide repeat (DPR) proteins, such as poly(proline-arginine) (polyPR) generated from G4C2 repeat expansions, have been shown to be highly toxic. In this study, PR20 was labeled with fluorescein isothiocyanate (FITC) to track its cellular localization. Several cell lines demonstrated survival under PR20 treatment by sequestering PR20 in the cytoplasm. Treatment with JQ-1 or Ivermectin (Iver) translocated PR20 into the nucleus, leading to cell death. Mechanistically, KPNA2/KPNB1 interacted with PR20 in the cytoplasm and hindered PR20 from entering the cell nucleus. Genetic silencing of KPNA2/KPNB1 converted PR20-resistant cells into PR20-sensitive cells. Treatment with JQ1 significantly reduced the protein levels of KPNA2/KPNB1, allowing PR20 to enter the nucleus. Overexpression of KPNA2 or KPNB1 effectively blocked cell death induced by co-treatment with JQ-1 and PR20. Our results indicate that super-enhancers shield cells from PR20 toxicity by upregulating the expression of KPNA2/KPNB1.}, } @article {pmid39891231, year = {2025}, author = {Rakab, MS and Zaid, AB and Hamadein, MA and Hamadein, SA and Ashour, MAE and El-Shamia, AS and Mostafa, DA and Rateb, RM and Elashry, MA and El-Badawy, MM and Shaheen, RSB}, title = {Assessment of ABCDE approach knowledge among residents and interns in multiple Egyptian hospitals, a cross-sectional study.}, journal = {BMC medical education}, volume = {25}, number = {1}, pages = {164}, pmid = {39891231}, issn = {1472-6920}, mesh = {Humans ; *Internship and Residency ; Egypt ; Cross-Sectional Studies ; Male ; Female ; Adult ; *Clinical Competence ; Surveys and Questionnaires ; *Health Knowledge, Attitudes, Practice ; }, abstract = {BACKGROUND: The Airway, Breathing, Circulation, Disability, and Exposure (ABCDE) approach is crucial in emergency care, but there may be variability in adherence among healthcare professionals. Inconsistent application of this approach may lead to variations in patient care quality and outcomes. Identifying the factors influencing adherence can help improve training to ensure more effective application across emergency settings. This study explores the theoretical knowledge of the ABCDE approach among Egyptian resident doctors and medical interns.

METHODS: An online survey was conducted in Egypt targeting resident doctors and medical interns. Statistical analyses were performed using SPSS 26 and Excel, descriptive statistics and association tests were used to measure the relationship between knowledge and demographic factors.

RESULTS: The study included 422 medical residents and interns, with most in university hospitals. The average knowledge score of 59.1% exposed specific gaps in understanding, emphasizing deficiencies in 12 questions answered by less than 50%. Notably, 49.5% acquired ABCDE knowledge from medical school, while 28.2% had ALS/BLS courses. Encouragingly, 91.2% expressed willingness for life support training. Statistical analyses unveiled significant associations between knowledge scores and both medical practice settings and sources of ABCDE knowledge. Surgeons exhibited the lowest knowledge scores among participants, emphasizing the need for tailored interventions across specialties.

CONCLUSION: This study addresses a critical gap in ABCDE approach knowledge among Egyptian resident doctors and medical interns. The study points to the need for focused education, especially for surgeons, to improve emergency care skills and patient outcomes through continued training.}, } @article {pmid39889925, year = {2025}, author = {Bian, Y and Fukui, Y and Ota-Elliott, RS and Hu, X and Sun, H and Bian, Z and Zhai, Y and Yu, H and Hu, X and An, H and Liu, H and Morihara, R and Ishiura, H and Yamashita, T}, title = {The potential mechanism maintaining transactive response DNA binding protein 43 kDa in the mouse stroke model.}, journal = {Neuroscience research}, volume = {213}, number = {}, pages = {128-137}, doi = {10.1016/j.neures.2025.01.006}, pmid = {39889925}, issn = {1872-8111}, mesh = {Animals ; Male ; Mice, Inbred C57BL ; *DNA-Binding Proteins/metabolism ; Disease Models, Animal ; Histone Deacetylase 6/metabolism ; Mice ; Infarction, Middle Cerebral Artery/metabolism/pathology ; *Stroke/metabolism/pathology ; *Brain/metabolism/pathology ; DNA Helicases/metabolism ; RNA Recognition Motif Proteins/metabolism ; }, abstract = {The disruption of transactive response DNA binding protein 43 kDa (TDP-43) shuttling leads to the depletion of nuclear localization and the cytoplasmic accumulation of TDP-43. We aimed to evaluate the mechanism underlying the behavior of TDP-43 in ischemic stroke. Adult male C57BL/6 J mice were subjected to 30 or 60 min of transient middle cerebral artery occlusion (tMCAO), and examined at 1, 6, and 24 h post reperfusion. Immunostaining was used to evaluate the expression of TDP-43, G3BP1, HDAC6, and RAD23B. The total and cytoplasmic number of TDP-43-positive cells increased compared with sham operation group and peaked at 6 h post reperfusion after tMCAO. The elevated expression of G3BP1 protein peaked at 6 h after reperfusion and decreased at 24 h after reperfusion in ischemic mice brains. We also observed an increase of expression level of HDAC6 and the number of RAD23B-positive cells increased after tMCAO. RAD23B was colocalized with TDP-43 24 h after tMCAO. We proposed that the formation of stress granules might be involved in the mislocalization of TDP-43, based on an evaluation of G3BP1 and HDAC6. Subsequently, RAD23B, may also contribute to the downstream degradation of mislocalized TDP-43 in mice tMCAO model.}, } @article {pmid39889542, year = {2025}, author = {Albrecht, F and Kvist, A and Franzén, E}, title = {Resting-state functional near-infrared spectroscopy in neurodegenerative diseases - A systematic review.}, journal = {NeuroImage. Clinical}, volume = {45}, number = {}, pages = {103733}, pmid = {39889542}, issn = {2213-1582}, mesh = {Humans ; Spectroscopy, Near-Infrared/methods ; *Neurodegenerative Diseases/diagnostic imaging/physiopathology ; *Brain/diagnostic imaging/physiopathology ; Rest/physiology ; *Functional Neuroimaging/methods ; }, abstract = {OBJECTIVE: To systematically review and summarize alterations found in resting-state activity as measured via functional near-infrared spectroscopy (fNIRS) in neurodegenerative diseases.

BACKGROUND: fNIRS is a novel and emerging neuroimaging method suitable for a variety of study designs. Resting-state is the measure of brain activity in the absence of a task, which has been investigated for yielding information about neurodegenerative diseases, mainly using magnetic resonance imaging. We aimed to systematically review the usage of resting-state fNIRS (rsfNIRS) in neurodegenerative diseases.

INCLUSION CRITERIA: Studies investigating people diagnosed with a neurodegenerative disease and resting-state activity obtained with fNIRS using at least two channels.

METHODS: We searched three databases for publications. After the screening, 16 studies were included in the systematic review. The quality of the studies was assessed, and data were extracted. Data were qualitatively synthesized and in the case of at least 10 similar studies, a meta-analysis was planned.

RESULTS: Most studies investigated Mild cognitive impairment (50%), followed by Alzheimer's disease (25%). Other neurodegenerative diseases encompassed Parkinson's disease, Multiple sclerosis, and Amyotrophic lateral sclerosis. All studies reported oxygenated hemoglobin. Still, studies were heterogeneous in terms of study design, measurement duration, fNIRS device, montage, pre-processing, and analyses. A meta-analysis was not considered possible due to this heterogeneity.

CONCLUSION: rsfNIRS shows promise in neurodegenerative disease, as most studies have observed resting-state alterations when compared to healthy controls. However, inconsistencies across studies limit data comparison and meta-analysis. Hence, we strongly advocate the application of fNIRS reporting guidelines and the establishment of rsfNIRS-specific guidelines. This will ensure reliable and comparable results in future research.}, } @article {pmid39889424, year = {2025}, author = {Pascual, A and May, PB and Cárdenas-Martínez, A and Guerra-Hernández, J and Hunka, N and Bruening, JM and Healey, SP and Armston, JD and Dubayah, RO}, title = {Calibration of GEDI footprint aboveground biomass models in Mediterranean forests with NFI plots: A comparison of approaches.}, journal = {Journal of environmental management}, volume = {375}, number = {}, pages = {124313}, doi = {10.1016/j.jenvman.2025.124313}, pmid = {39889424}, issn = {1095-8630}, mesh = {*Biomass ; *Forests ; Calibration ; Ecosystem ; Spain ; Models, Theoretical ; }, abstract = {Observations from the NASA Global Ecosystem Dynamics Investigation (GEDI) provide global information on forest structure and biomass. Footprint-level predictions of aboveground biomass density (AGBD) in the GEDI mission are based on training data sourced from sparsely distributed field plots coincident with airborne laser scanning surveys. National Forest Inventories (NFI) are rarely used to calibrate GEDI footprint biomass models because their sampling and positional accuracy prevent accurate colocation with GEDI or ALS. This omission can limit the harmonization of jurisdictional biomass estimates from NFI's and GEDI; however, there are methods available to improve the colocation of NFI plots with GEDI footprints. Focusing on Mediterranean forests in Spain, we compared different approaches to the collocation of NFI and GEDI data: (i) simulated waveforms from ALS; (ii) nearest-neighbor on-orbit GEDI waveforms; and (iii) imputed GEDI waveforms imputed to NFI plot locations using a novel geostatistical method. These methods are potential solutions to improve the local performance of biomass models and address potential local systematic deviations between GEDI and NFI estimates. We assess the advantages and limitations of these methods to locally calibrate GEDI biomass models and quantify the impact of geolocation errors in reference NFI plot data. The new biomass models from each method were used to predict footprint level AGBD, which were then gridded for a province in the North-West of Spain. It was found that the imputation approach is not sensitive to common errors in NFI plot geolocation, but it can outperform ALS-based simulation in some cases, highlighting the benefit of information from multiple GEDI footprints proximate to NFI plots for improving biomass predictions. This research provides users with benchmark of available techniques to locally-calibrate GEDI footprint biomass models.}, } @article {pmid39887552, year = {2025}, author = {Dopler, MB and Abeer, MI and Arezoumandan, S and Cox, K and Petersen, TL and Daniel, EH and Cannon, CL and Bautista, A and Blancher, KD and Bland, AM and Bond, KJ and Davis, DA and Francois, JM and McCray, EJ and Morgan, JM and Pulliam, JL and Robinson, ZA and Taylor, MJ and Dowell, JA and Cairns, NJ and Gitcho, MA}, title = {A cellular model of TDP-43 induces phosphorylated TDP-43 aggregation with distinct changes in solubility and autophagy dysregulation.}, journal = {The FEBS journal}, volume = {}, number = {}, pages = {}, pmid = {39887552}, issn = {1742-4658}, support = {52008702//HHMI/ ; 2023004//National Science Foundation/ ; P30 GM145765/GM/NIGMS NIH HHS/United States ; P20GM103446/GM/NIGMS NIH HHS/United States ; P20 GM103446/GM/NIGMS NIH HHS/United States ; 0823//The Paul H. Boerger Fund of the Delaware Community Foundation/ ; P20 GM103653/GM/NIGMS NIH HHS/United States ; R25 GM122722/GM/NIGMS NIH HHS/United States ; P20GM103653/GM/NIGMS NIH HHS/United States ; T32GM144895-03/GM/NIGMS NIH HHS/United States ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease that affects neurons in the brain and spinal cord, causing loss of muscle control, and eventually leads to death. Phosphorylated transactive response DNA binding protein-43 (TDP-43) is the major pathological protein in both sporadic and familial ALS, forming cytoplasmic aggregates in over 95% of cases. Of the 10-15% of ALS cases that are familial, mutations in TDP-43 represent about 5% of those with a family history. We have developed an in vitro overexpression model by introducing three familial ALS mutations (A315T, M337V, and S379P) in the TDP-43 (TARDBP) gene which we define as 3X-TDP-43. This overexpression model TDP-43 shows deficits in autophagy flux and colocalization of TDP-43 with stress granules. We also observe a progressive shift of TDP-43 to the cytoplasm in this model. This overexpression model shows a reduction in solubility of phosphorylated TDP-43 from RIPA to urea soluble. Four glycolytic enzymes, phosphoglycerate kinase one (PGK1), aldolase A (ALDOA), enolase 1 (ENO1), and pyruvate dehydrogenase kinase 1 (PDK1) show significant time-dependent decreases in 3X-TDP-43 expressing cells. Shotgun proteomic analysis shows global changes in the importin subunit alpha-1 (KPNA2), heat shock 70 kDa protein 1A (HSPA1A), and protein disulfide-isomerase A3 (PDIA3) expression levels and coimmunoprecipitation reveals that these proteins complex with TDP-43. Overall, these results suggest that the 3X-TDP-43 model may provide new insights into pathophysiology and an avenue for drug screening in vitro for those suffering from ALS and related TDP-43 proteinopathies.}, } @article {pmid39886777, year = {2025}, author = {Alkhazaali-Ali, Z and Sahab-Negah, S and Boroumand, AR and Farkhad, NK and Khodadoust, MA and Ganjali, R and Tavakol-Afshari, J}, title = {Evaluation of Safety and Efficacy of Repeated Mesenchymal Stem Cell Transplantation in Patients with Amyotrophic Lateral Sclerosis (ALS) by Investigating Patient's Specific microRNAs as Novel Biomarkers: A Clinical Trial Study.}, journal = {Current stem cell research & therapy}, volume = {}, number = {}, pages = {}, doi = {10.2174/011574888X330199250106081717}, pmid = {39886777}, issn = {2212-3946}, abstract = {BACKGROUND: Since there is currently no cure for amyotrophic lateral sclerosis (ALS), it is essential to search for diagnostic biomarkers and novel treatments to reduce the severity of this disease. One of these treatment approaches is stem cell transplantation.

OBJECTIVE: This study aims to evaluate the safety and efficacy of repeated transplantation of autologous bone marrow-derived mesenchymal stem cells (BM-MSCs) in patients with ALS by analyzing clinical and molecular data.

METHODS: This one-arm, single-center, open-label without a control group, prospective clinical trial, twenty-one confirmed ALS patients entered the study based on defined inclusion and exclusion criteria and underwent repeated stem cell transplantation (3 times BM-MSCs transplantation (1×10^6, MSC/Kg BW per injection) concurrently intrathecally (IT) and intravenously (IV), with one-month interval). Clinical assessment using ALS functional rating scale-revised (ALSFRS) and forced vital capacity (FVC) values and also molecular investigation by evaluating specific microRNAs expression (mir206, 133a-3p, 338-3p) in patient's serum and Cerebra spinal fluid (CSF) samples were done three times during the 3-month follow-up period.

RESULT: No serious adverse effects were reported during the study. Besides, significant improvement in FVC when compared the baseline with the end of the research and the p-value was (0.036), and stability in ALSFRS was observed, and the p-value was (p=0.16) following stem cell transplantation in patients; also, the mentioned microRNA expression was non-significant (p > 0.05) as reported as well.

CONCLUSION: Our results demonstrated that repeated transplantation of BM-MSCs was a safe procedure in ALS patients, leading to delay in disease progression and improvement in clinical symptoms. Future studies are needed to confirm these results.}, } @article {pmid39885830, year = {2025}, author = {Marthinsen, A and Gaweł, BA and Warden, GK and Górska-Ratusznik, A and Gaweł, K and Di Sabatino, M and Hallam, B}, title = {Al doped silica glass: investigation of structural response and defect interactions based on crystalline models.}, journal = {Physical chemistry chemical physics : PCCP}, volume = {27}, number = {7}, pages = {3803-3809}, doi = {10.1039/d4cp04581e}, pmid = {39885830}, issn = {1463-9084}, abstract = {High purity quartz glass is an important material in high-tech industries like semiconductors and photovoltaics due to, among other properties, its good mechanical performance at high temperatures. Small amounts of Al in silica glass (in the range between 20 ppm and 100 ppm) have previously been shown to increase the viscosity of the SiO2 glass. The underlying mechanism for this increase is, however, not well understood. In this paper we report on the local structural and electronic effects of the presence of Al in the SiO2 structure by density functional theory (DFT). Comparing the quartz and cristobalite polymorphs, we found that the driving force for Al substitution is larger in the denser quartz structure compared to cristobalite, and that oxygen vacancy (Vo) formation is most stabilized in the nearest neighbour position relative to Al in both polymorphs. Al was not found to inherently strengthen the SiO2 network in the two crystalline polymorphs considered. However, our results suggest that Al preferentially substitutes Si in denser ring configurations, which combined with local Vo formation could lead to locally favourable SiO2 network reconstructions in SiO2 glasses (likely towards 6-membered rings), which could propagate causing an increase in the viscosity. Furthermore, we show that the presence of Al can lower the stability of OH groups due to increased electrostatic interactions between the substitutional Al and H2O which may also be a contributing factor in the increased viscosity of Al doped SiO2 glass. The modelling results are in line with the experimental fluorescence and FT-IR spectroscopy data confirming that the presence of Al in the glass causes formation of oxygen vacancies and correlates with a lower fictive temperature which typically corresponds to a larger average Si-O-Si angle in the glass structure. Our results suggest that Al's contribution to high glass viscosity is not solely due to the substitution of Si atoms by Al atoms in the glass structure but rather due to structural changes of the silica network the substitution causes.}, } @article {pmid39885728, year = {2025}, author = {Gondim, F and Fernandes, JMA}, title = {Another family with ALS and homozygosity for p.Val120Leu (c.358G > C) mutation of SOD1.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {26}, number = {5-6}, pages = {597-598}, doi = {10.1080/21678421.2025.2457973}, pmid = {39885728}, issn = {2167-9223}, } @article {pmid39884586, year = {2025}, author = {Ye, L and Dittlau, KS and Sicart, A and Janky, R and Van Damme, P and Van Den Bosch, L}, title = {Sporadic ALS hiPSC-derived motor neurons show axonal defects linked to altered axon guidance pathways.}, journal = {Neurobiology of disease}, volume = {206}, number = {}, pages = {106815}, doi = {10.1016/j.nbd.2025.106815}, pmid = {39884586}, issn = {1095-953X}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/pathology/metabolism ; *Induced Pluripotent Stem Cells/pathology/metabolism ; *Motor Neurons/pathology/metabolism ; *Axon Guidance/physiology ; *Axons/pathology/metabolism ; Axonal Transport/physiology ; Female ; Male ; Neuromuscular Junction/pathology ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder characterized by the selective and progressive loss of motor neurons, leading to gradual paralysis and death within 2 to 5 years after diagnosis. The exact underlying pathogenic mechanism(s) remain elusive. This is particularly the case for sporadic ALS (sALS), representing 90 % of cases, as modelling a sporadic disease is extremely difficult. We used human induced pluripotent stem cell (hiPSC)-derived motor neurons from sALS patients to investigate early disease mechanisms. The earliest phenotype that we observed were profound axonal defects including impaired axonal transport, defective axonal outgrowth and a reduced formation of neuromuscular junctions. Transcriptomic profiling revealed significant dysregulation in axon guidance pathways, with upregulation of specific axonal regeneration-inhibiting genes, such as EphA4 and DCC in sALS motor neurons. Our findings suggest that dysregulation of axon guidance pathways contributes to axonal defects and that this could play a crucial role in the pathogenesis of sALS.}, } @article {pmid39884579, year = {2025}, author = {Liu, WW and Wei, JC}, title = {Response to Vera et al's "Interleukin-23 inhibition associates with lower incidence of cardiovascular risk factor type diseases compared to biologic naïve patients with psoriasis: A retrospective cohort study".}, journal = {Journal of the American Academy of Dermatology}, volume = {92}, number = {5}, pages = {e157-e158}, doi = {10.1016/j.jaad.2024.12.044}, pmid = {39884579}, issn = {1097-6787}, } @article {pmid39883905, year = {2025}, author = {Hollin, IL and Giler, G and Heiman-Patterson, TD and , }, title = {Health Care Delivery and Financial Considerations in Amyotrophic Lateral Sclerosis Clinics: A Survey of Clinic Directors.}, journal = {Neurology}, volume = {104}, number = {4}, pages = {e210015}, pmid = {39883905}, issn = {1526-632X}, mesh = {*Amyotrophic Lateral Sclerosis/therapy/economics ; Humans ; *Delivery of Health Care/economics ; Surveys and Questionnaires ; United States ; *Ambulatory Care Facilities/economics ; }, abstract = {BACKGROUND AND OBJECTIVES: Clinical care for people living with amyotrophic lateral sclerosis (PLWALS) is directed at slowing disease progression and symptom management. The American Academy of Neurology recommends a multidisciplinary approach to providing ALS health care because observational studies show that multidisciplinary clinics (MDCs) extend survival and improve quality of life. However, providing multidisciplinary care is a challenging financial proposition. To understand how MDCs are financed, we surveyed ALS MDCs across the Northeast ALS Consortium network in the United States.

METHODS: We surveyed clinic directors in the Northeast ALS Consortium, a group of institutions equipped to provide ALS care and perform research and clinical trials in ALS. Respondents (n = 61; response rate = 49.6%) provided information regarding their care model, services, funding sources, and financial solvency between December 2020 and August 2021.

RESULTS: In 74% (n = 45) of clinics, PLWALS were seen by the entire multidisciplinary team, and in 26% (n = 16) of clinics, PLWALS were seen by the physician and triaged according to needs. In 79% (n = 48) of clinics, visit duration was ≥3 hours, and on average, 8.4 services were available, compared with 6.8 in clinics lasting <3 hours. Most of the MDCs offer occupational (97%; n = 59), speech (97%; n = 59), and physical (95%; n = 58) therapies on site. The most common source of financial support was third-party nonprofits/philanthropy (92%; n = 56). Fifty-nine percent (n = 36) of clinics received financial support from their parent organizations (e.g., universities). Only 17% (n = 10) of clinics reported no deficit, and all clinics used multiple income sources.

DISCUSSION: These findings reconfirm the range of services available to PLWALS and highlight the financial challenges facing ALS MDCs. The main limitation is that recruitment was through the NEALS network which primarily includes MDCs, so we were not able to compare with non-MDCs. Since not all centers responded, there may be other differences in the characteristics of the centers that did respond and those that did not leading to some bias. Future work should support the goal of reducing reliance on funding from nonprofits and increase reimbursement from payers, so health care providers can provide high-quality ALS care and cover costs.}, } @article {pmid39883903, year = {2025}, author = {Fournier, CN and Quinn, CC}, title = {The Amyotrophic Lateral Sclerosis Multidisciplinary Clinic: Broke but Not Broken.}, journal = {Neurology}, volume = {104}, number = {4}, pages = {e210189}, doi = {10.1212/WNL.0000000000210189}, pmid = {39883903}, issn = {1526-632X}, } @article {pmid39882923, year = {2025}, author = {Koltsova, E and Smotraiev, R and Nehrii, A and Zhekeev, M and Ratnaweera, H}, title = {Mechanisms for removing phosphorus species through sequential coagulation using inorganic coagulants and organic polymers.}, journal = {Water science and technology : a journal of the International Association on Water Pollution Research}, volume = {91}, number = {2}, pages = {202-218}, pmid = {39882923}, issn = {0273-1223}, mesh = {*Phosphorus/chemistry/isolation & purification ; *Polymers/chemistry ; *Water Pollutants, Chemical/chemistry/isolation & purification ; Alum Compounds/chemistry ; *Waste Disposal, Fluid/methods ; *Water Purification/methods ; Flocculation ; Phosphates/chemistry ; }, abstract = {The need for stringent phosphorus removal from domestic wastewater is increasing to mitigate eutrophication, while efficient phosphate reuse is critical due to the global phosphate crisis. Combining aluminum sulfate (ALS) with high molecular weight organic polymers achieved 95-99% removal of particles, turbidity, and phosphates, reducing ALS usage by 40%. We propose mechanisms to explain the enhanced treatment efficiency. Particle and turbidity removal is more influenced by polymer charge density than molecular weight, while orthophosphate (OP) removal is linked to a change in zeta potential from negative to positive, allowing additional OP binding through complex formation with hydrolysis products and polymers. Enhanced phospholipid (PL) removal likely results from adsorption and neutralization of micelle PL charges by intermediate positively charged aluminum hydroxyphosphate ions. Higher PL removal with low ALS doses is attributed to a two-stage dosing process that optimizes coagulant and polymer dosages. The combined removal of OP and PL improves phosphorus bioavailability, increasing the sludge's fertilizer value.}, } @article {pmid39882298, year = {2024}, author = {Johnsen, JT and Rafaela Lima do Vale, M and Bhangaonkar, R and Nyaga, W and Ayyad, S and Ray, S}, title = {COVID-19's impact on food environment in the Indian states of Telangana, Maharashtra, West Bengal, Tamil Nadu and Punjab: a descriptive qualitative study to build further research in India's food environment resilience building.}, journal = {BMJ nutrition, prevention & health}, volume = {7}, number = {2}, pages = {e000844}, pmid = {39882298}, issn = {2516-5542}, abstract = {BACKGROUND AND AIM: Globally, COVID-19 has had a profound impact on food and nutrition security. This paper aims to gather the perspective from Transforming India's Green Revolution by Research and Empowerment for Sustainable food Supplies (TIGR2ESS) Flagship Project 6 (FP-6) team on the impact of COVID-19 on the food systems in India. The responses collected will be used for further research projects after TIGR2ESS ends in March 2022.

METHOD: Members of the TIGR2ESS FP-6 team in India were invited to complete an online open-ended questionnaire with 21 questions exploring the impact of the COVID-19 pandemic on food systems and environments in India. The questionnaire and data analysis were guided by the food environment framework developed by Turner et al and the adaptations proposed by the United Nations System Standing Committee on Nutrition. Discussions and organisation of codes under the respective themes and subthemes were held online using the virtual platform Miro. 35 individual codes and 65 subcodes were agreed on. Responses were collated and analysed using the template with support from NVivo software and synthesised the relevant themes under Turner et al's framework.

RESULTS: The organisation representatives from TIGR2ESS FP-6 (n=16) captured the perceived impact of the COVID-19 on food systems and the environment from the Indian states of Maharashtra, Punjab, Tamil Nadu, Telangana and West Bengal. Negative disruptions were caused by the COVID-19 restrictions across all the themes affecting food actors and consumers. Myths and misconception on dietary intake were reported across the state affecting especially the consumption of poultry. Positive aspects such as home cooking and awareness around healthy food emerged.

CONCLUSION: Potential research areas were identified and involve the effects of supply chain resilience buidling, farmers selling their produce directly to consumer and the revival of local and traditional food's impact on diets, understanding the harm for consumers by implementing restrictions, how indigenous and local food may impact peoples' diets, how to build on the encouragement of healthy home cooking during the pandemic, investigate the negative and positive effects of digital environments during the pandemic and dispelling myths and misconception while advocating for healthy diets.}, } @article {pmid39881481, year = {2025}, author = {Steenland, K and Tan, Y and Mullins, SM and Kidd, TE and Gong, Q and Lah, JJ}, title = {Survival of Patients at a Neurology Clinic: No Improvement Over 12 Years.}, journal = {Alzheimer disease and associated disorders}, volume = {39}, number = {1}, pages = {28-32}, doi = {10.1097/WAD.0000000000000658}, pmid = {39881481}, issn = {1546-4156}, mesh = {Humans ; Female ; Male ; Aged ; *Neurodegenerative Diseases/mortality ; Middle Aged ; Neurology ; Aged, 80 and over ; Dementia/mortality ; Neuropsychological Tests ; Cognitive Dysfunction/mortality ; }, abstract = {INTRODUCTION: We previously followed Emory patients with neurodegenerative disease from 1993 to 2006. Here, we follow survivor and new patients for 2007 to 2018.

METHODS: We studied mortality from 10 different diagnostic groups among 4322 research volunteers, and compared mortality rates to controls with normal cognition, using Cox regression. We assessed mortality through the National Death Index, controlling for sex, education, race, comorbidities, and age. Supplemental analyses considered APOE and cognitive test scores.

RESULTS: Fifty-nine percent of patients died during follow-up. Mortality rate ratios, compared with controls (n=641) in descending order were 12.54, 6.61, 4.77, 4.92, 3.36, 2.25, 2.21 1.71, 1.39, and 1.17 for diagnostic groups ALS, (n=571), FTD (n=197), LBD (n=134), PD (n=584), AD (n=1118), MCI/dementia (n=82), dementia not specified (n=165), PD symptoms (n=256), vascular dementia (n=234), and MCI (n=340), respectively. Women, non-whites, those with higher education, with no comorbidities, and lower ages had lower mortality rates for most diagnostic groups. Mortality rates were higher in the presence of APOE4 variants for several diagnostic groups. Lower MMSEs predicted worse survival for most diseases. Overall, 41% of patients survived during 12 years of follow-up, compared with an expected 75% in the US population.

CONCLUSION: Survival times for different diagnostic groups have changed little over several decades.}, } @article {pmid39880678, year = {2025}, author = {Kozlowski, MM and Strickland, A and Benitez, AM and Schmidt, RE and Bloom, AJ and Milbrandt, J and DiAntonio, A}, title = {Pmp2+ Schwann Cells Maintain the Survival of Large-Caliber Motor Axons.}, journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, volume = {45}, number = {13}, pages = {}, pmid = {39880678}, issn = {1529-2401}, support = {R01 NS105645/NS/NINDS NIH HHS/United States ; R37 NS065053/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; *Schwann Cells/metabolism/physiology/ultrastructure ; Mice ; *Axons/physiology/ultrastructure/metabolism ; Female ; Male ; *Motor Neurons/physiology/ultrastructure/metabolism ; Cell Survival/physiology ; Mice, Transgenic ; *Myelin Proteins/metabolism/genetics ; Mice, Inbred C57BL ; Tamoxifen/pharmacology ; }, abstract = {Neurodegenerative diseases of both the central and peripheral nervous system are characterized by selective neuronal vulnerability, i.e., pathology that affects particular types of neurons. While much of this cell type selectivity may be driven by intrinsic differences among the neuron subpopulations, neuron-extrinsic mechanisms such as the selective malfunction of glial support cells may also play a role. Recently, we identified a population of Schwann cells (SCs) expressing Adamtsl1, Cldn14, and Pmp2 (a.k.a. PMP2+ SCs) that preferentially myelinate large-caliber motor axons. PMP2+ SCs are decreased in both amyotrophic lateral sclerosis (ALS) model mice and ALS patient nerves. Thus, PMP2+ SC dysfunction could contribute to motor-selective neuropathies. We engineered a tamoxifen-inducible Pmp2-CreERT2 mouse and expressed diphtheria toxin in PMP2+ SCs to assess the consequences of ablating this SC subtype in male and female mice. Loss of PMP2+ SCs led to significant loss of large-caliber motor axons with concomitant behavioral, electrophysiological, and ultrastructural defects. Subsequent withdrawal of tamoxifen restored both PMP2+ SCs and large-caliber motor axons and improved behavioral and electrophysiological readouts. Together, our findings highlight that the survival of large-caliber motor axons relies on PMP2+ SCs, demonstrating that malfunction of a specific SC subtype can lead to selective neuronal vulnerability.}, } @article {pmid39880333, year = {2025}, author = {Izrael, M and Chebath, J and Molakandov, K and Revel, M}, title = {Clinical perspective on pluripotent stem cells derived cell therapies for the treatment of neurodegenerative diseases.}, journal = {Advanced drug delivery reviews}, volume = {218}, number = {}, pages = {115525}, doi = {10.1016/j.addr.2025.115525}, pmid = {39880333}, issn = {1872-8294}, mesh = {Humans ; *Neurodegenerative Diseases/therapy ; *Pluripotent Stem Cells/transplantation/cytology ; Animals ; *Cell- and Tissue-Based Therapy/methods ; *Stem Cell Transplantation/methods ; Clinical Trials as Topic ; }, abstract = {Self-renewal capacity and potential to differentiate into almost any cell type of the human body makes pluripotent stem cells a valuable starting material for manufacturing of clinical grade cell therapies. Neurodegenerative diseases are characterized by gradual loss of structure or function of neurons, often leading to neuronal death. This results in gradual decline of cognitive, motor, and physiological functions due to the degeneration of the central nervous systems. Over the past two decades, comprehensive preclinical efficacy (proof-of-concept) and safety studies have led to the initiation of First-in-Human phase I-II clinical trials for a range of neurodegenerative diseases. In this review, we explore the fundamentals and challenges of neural-cell therapies derived from pluripotent stem cells for treating neurodegenerative diseases. Additionally, we highlight key preclinical investigations that paved the way for regulatory approvals of these trials. Furthermore, we provide an overview on progress and status of clinical trials done so far in treating neurodegenerative diseases such as spinal cord injury (SCI), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS), as well as advances in retina diseases such as Stargardt disease (a.k.a fundus flavimaculatus), retinitis pigmentosa (RP) and age-related macular degeneration (AMD). These trials will pave the way for the development of new cell-based therapies targeting additional neurological conditions, including Alzheimer's disease and epilepsy.}, } @article {pmid39880289, year = {2025}, author = {Chen, SJ and Li, QY and Zhou, J and Wu, Q and Zhang, Y and Zhang, QQ and Hu, H and Xu, XQ and Wu, FY and Niu, Q}, title = {Differed brain spontaneous neural activity between limb-onset and bulbar-onset amyotrophic lateral sclerosis patients.}, journal = {Brain research bulletin}, volume = {221}, number = {}, pages = {111229}, doi = {10.1016/j.brainresbull.2025.111229}, pmid = {39880289}, issn = {1873-2747}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology/diagnostic imaging ; Male ; Female ; Middle Aged ; Magnetic Resonance Imaging/methods ; *Brain/physiopathology/diagnostic imaging ; Aged ; Adult ; Brain Mapping/methods ; Support Vector Machine ; }, abstract = {PURPOSE: To investigate the differences in brain spontaneous neural activity between limb-onset and bulbar-onset amyotrophic lateral sclerosis (ALS-L and ALS-B, respectively) patients using resting-state functional MRI (rs-fMRI) with amplitude of low-frequency fluctuation (ALFF) and regional homogeneity (ReHo).

MATERIALS AND METHODS: The rs-fMRI data were collected from 41 ALS patients (11 ALS-B and 30 ALS-L) and 25 healthy controls (HC). ALFF and ReHo values were calculated, and group differences were assessed using one-way ANCOVA and two-sample t-tests. Correlation analyses with clinical measures were conducted. Support vector machine (SVM) analysis was performed to distinguish ALS subtypes.

RESULTS: Compared with ALS-L, ALS-B showed increased ALFF values in the right gyrus rectus/ orbital part of right middle frontal gyrus, orbital part of left middle frontal gyrus and left dorsolateral superior frontal gyrus/ left medial superior frontal gyrus and decreased ALFF values in the left superior occipital gyrus (FDR-corrected, P < 0.05). Both ALS subtypes demonstrated distinct ALFF alterations compared to HC. Differences in ReHo values were only found between ALS-B and HC. Correlation analyses revealed associations between ALFF in specific brain regions and ALS clinical scores. SVM analysis achieved an accuracy of 90.2 %, with an AUC of 0.909 in differentiating ALS-B and ALS-L.

CONCLUSION: ALS-B and ALS-L patients had distinct alterations in brain spontaneous neural activity, which could serve as potential biomarkers for accurately distinguishing these two subtypes. Our findings offer a new insight into the neural mechanism of ALS, underscoring the importance of personalized diagnostic approaches for this complex neurological disorder.}, } @article {pmid39880202, year = {2025}, author = {Xu, F and Liu, H and Yin, Z and Xing, X and Chen, X}, title = {Associations of dietary factors with amyotrophic lateral sclerosis: A Mendelian randomization study.}, journal = {Clinical nutrition ESPEN}, volume = {66}, number = {}, pages = {226-235}, doi = {10.1016/j.clnesp.2025.01.042}, pmid = {39880202}, issn = {2405-4577}, mesh = {*Amyotrophic Lateral Sclerosis/genetics/prevention & control/epidemiology ; Humans ; *Mendelian Randomization Analysis ; *Diet ; Genome-Wide Association Study ; Fruit ; Vegetables ; Risk Factors ; *Feeding Behavior ; Polymorphism, Single Nucleotide ; }, abstract = {BACKGROUND: An inconsistent yet notable relationship between dietary habits and the risk of amyotrophic lateral sclerosis (ALS) has been previously established, with the causative nature of this relationship remaining uncertain. This study aims to explore the causal connections at a genetic level.

METHODS: A two-sample Mendelian Randomization (MR) based analysis was conducted utilizing a comprehensive, publicly assessable Genome-wide association study (GWAS) database. Fourteen dietary variables were examined as potential exposure factors, and the ALS outcome data was statistically analyzed. The inverse-variance weighted (IVW) approach was used as the primary analytical method, supplemented by sensitivity analyses to assess the reliability of our findings.

RESULTS: Our analysis identified significant protective effects against ALS from increased intake of water (fixed-effects IVW: OR = 0.700, 95 % CI: 0.524-0.935, P = 0.016), fresh fruit (random-effects IVW: OR = 0.561, 95 % CI: 0.361-0.871, P = 0.010), and cooked vegetable (fixed-effects IVW: OR = 0.200, 95 % CI: 0.090-0.445, P = 0.000). No significant associations were found for the other 11 dietary factors examined.

CONCLUSION: The study highlights the protective association of cooked vegetables and fresh fruit intake with ALS risk reduction. Additionally, an intriguing association between water intake and ALS was observed, warranting further investigation to elucidate the underlying mechanisms.}, } @article {pmid39879721, year = {2025}, author = {Derevyanko, A and Tao, T and Allen, NJ}, title = {Common alterations to astrocytes across neurodegenerative disorders.}, journal = {Current opinion in neurobiology}, volume = {90}, number = {}, pages = {102970}, doi = {10.1016/j.conb.2025.102970}, pmid = {39879721}, issn = {1873-6882}, mesh = {Humans ; *Astrocytes/metabolism/pathology/immunology ; *Neurodegenerative Diseases/pathology/metabolism/immunology ; Animals ; *Brain/pathology/metabolism ; }, abstract = {Astrocytes perform multiple functions in the nervous system, many of which are altered in neurodegenerative disorders. In this review, we explore shared astrocytic alterations across neurodegenerative disorders, including Alzheimer's disease, Huntington's disease, Parkinson's disease, amyotrophic lateral sclerosis, and frontotemporal lobe degeneration. Assessing recent datasets of single-nucleus RNA-sequencing of human brains, a theme emerges of common alterations in astrocyte state across disorders including in neuroinflammation, synaptic organization, metabolic support, and the cellular stress response. Immune pathways are upregulated by astrocytes across disorders and may exacerbate neurodegeneration. Dysregulated expression of synaptogenic factors could contribute to synaptic loss, while compromised metabolic support affects neuronal homeostasis. On the other hand, upregulated responses to cellular stress may represent a protective response of astrocytes and thus mitigate pathology. Understanding these shared responses offers insights into disease progression and provides potential therapeutic targets for various neurodegenerative disorders.}, } @article {pmid39879575, year = {2025}, author = {Jang, DG and Kind, AJ and Patterson, A and Pedde, M and Powell, WR and Feldman, EL and Goutman, SA}, title = {Impact of the Adverse Social Exposome on Survival in Individuals With Amyotrophic Lateral Sclerosis.}, journal = {Neurology}, volume = {104}, number = {4}, pages = {e213362}, pmid = {39879575}, issn = {1526-632X}, support = {R01 TS000327/TS/ATSDR CDC HHS/United States ; K23 ES027221/ES/NIEHS NIH HHS/United States ; R01 ES030049/ES/NIEHS NIH HHS/United States ; R01 NS127188/NS/NINDS NIH HHS/United States ; R01 AG070883/AG/NIA NIH HHS/United States ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/mortality/psychology ; Female ; Male ; Aged ; Retrospective Studies ; Middle Aged ; Aged, 80 and over ; *Exposome ; Michigan/epidemiology ; }, abstract = {BACKGROUND AND OBJECTIVES: An adverse social exposome negatively affects many diseases, but its association with amyotrophic lateral sclerosis (ALS) survival is unknown. This study examined the association between the social exposome measure Area Deprivation Index (ADI) and ALS survival.

METHODS: This is a retrospective analysis of patients with ALS at the University of Michigan Pranger ALS Clinic diagnosed after January 1, 2012. Extracted data included age, sex, race, residential address, disease characteristics, and survival. National ADI ranking was assigned to each patient's geocoded address. Accelerated failure time survival analysis determined association between the ADI group and survival with adjustment for clinicodemographic covariates.

RESULTS: 1,085 patients (median age at diagnosis, 72 years; 45% female) met inclusion criteria. The highest ADI decile (most disadvantaged neighborhood group) was associated with 37.0% shorter survival time (95% CI -50.4% to -20.1%). Results were similar when grouping patients by ADI ranking (as opposed to decile) or including only those with a classical ALS phenotype.

DISCUSSION: Exposure to adverse social exposome, as measured by ADI, associates with poorer ALS survival. Because this is a single-center study, replication in other cohorts is encouraged. Further research is needed to understand the underlying mechanisms, which could influence ALS clinical care.}, } @article {pmid39879320, year = {2025}, author = {Guillot, SJ and Lang, C and Simonot, M and Beckett, D and Lulé, D and Balz, LT and Knehr, A and Stuart-Lopez, G and Vercruysse, P and Dieterlé, S and Weydt, P and Dorst, J and Kandler, K and Kassubek, J and Wassermann, L and Rouaux, C and Arthaud, S and Da Cruz, S and Luppi, PH and Roselli, F and Ludolph, AC and Dupuis, L and Bolborea, M}, title = {Early-onset sleep alterations found in patients with amyotrophic lateral sclerosis are ameliorated by orexin antagonist in mouse models.}, journal = {Science translational medicine}, volume = {17}, number = {783}, pages = {eadm7580}, doi = {10.1126/scitranslmed.adm7580}, pmid = {39879320}, issn = {1946-6242}, mesh = {Animals ; *Amyotrophic Lateral Sclerosis/physiopathology/complications/drug therapy ; Disease Models, Animal ; Humans ; *Orexins/antagonists & inhibitors/metabolism ; Mice ; *Sleep/drug effects ; Male ; *Orexin Receptor Antagonists/therapeutic use/pharmacology ; Female ; Melanins/pharmacology/therapeutic use ; Pituitary Hormones/pharmacology/therapeutic use ; Hypothalamic Hormones/pharmacology/therapeutic use/administration & dosage ; Motor Neurons/pathology/drug effects ; Wakefulness/drug effects ; Mice, Transgenic ; Middle Aged ; *Sleep Wake Disorders/drug therapy/complications/physiopathology ; Polysomnography ; }, abstract = {Sleep alterations have been described in several neurodegenerative diseases yet are currently poorly characterized in amyotrophic lateral sclerosis (ALS). This study investigates sleep macroarchitecture and related hypothalamic signaling disruptions in ALS. Using polysomnography, we found that both patients with ALS as well as asymptomatic C9ORF72 and SOD1 mutation carriers exhibited increased wakefulness and reduced non-rapid eye movement sleep. Increased wakefulness correlated with diminished cognitive performance in both clinical cohorts. Similar changes in sleep macroarchitecture were observed in three ALS mouse models (Sod1[G86R], Fus[ΔNLS/+], and TDP43[Q331K]). A single oral administration of a dual-orexin receptor antagonist or intracerebroventricular delivery of melanin-concentrating hormone (MCH) through an osmotic pump over 15 days partially normalized sleep patterns in mouse models. MCH treatment did not extend the survival of Sod1[G86R] mice but did decrease the loss of lumbar motor neurons. These findings suggest MCH and orexin signaling as potential targets to treat sleep alterations that arise in early stages of the disease.}, } @article {pmid39877726, year = {2025}, author = {Fournier, CN and Levine, M and Simmons, K and García-Santibáñez, RC and Rowland, A and Quinn, CC and Ho, DT and Bedlack, RS and Glass, JD}, title = {ALS Motor Observational Telemedicine Objective Rasch-Built Assessment: A Quantitative Scale for the Era of Teleneurology.}, journal = {Neurology. Clinical practice}, volume = {15}, number = {2}, pages = {e200432}, pmid = {39877726}, issn = {2163-0402}, abstract = {BACKGROUND AND OBJECTIVES: Telemedicine has become a mainstay of ALS clinical care, but there is currently no standardized approach for assessing and tracking changes to the neurologic examination in this format. The goal of this study was to create a standardized telemedicine-based motor examination scale to objectively and reliably track ALS progression and use Rasch methodology to validate the scale and improve its psychometric properties.

METHODS: A draft telemedicine examination scale with 25 items assessing movement in the bulbar muscles, neck, trunk, and extremities was created by an ALS expert panel, incorporating input from patient advisors. This prospective, observational study was approved by the Emory IRB, and participants provided informed consent. Adults with a diagnosis of ALS who were able to undergo a video telemedicine evaluation by an Emory clinician were eligible for participation. Rasch analyses were performed to determine the final item responses and optimize the scoring structure. Test-retest reliability was assessed in a subset of participants through 2 separate examinations by 2 different examiners within a 7-day period. Construct validity was assessed by calculating correlations with simultaneously administered Rasch-built Overall ALS Disability Scale (ROADS) and revised ALS Functional Rating Scale (ALSFRS-R).

RESULTS: The ALS Motor Observational Telemedicine Objective Rasch-built assessment was administered to a total of 258 PALS representing the full spectrum of a typical ALS clinic population. After performing Rasch analyses, 3 items were removed and item response categories were consolidated for 8 items. The final 22-item ALS MOTOR scale conformed to Rasch model criteria. The inter-rater reliability was 95%. The ALS MOTOR had a 0.78 (95% CI 0.72-0.83) correlation with ALSFRS-R and 0.81 (95% CI 0.76-0.85) correlation with ROADS.

DISCUSSION: The ALS MOTOR is a novel, accessible tool for remotely and objectively tracking ALS progression for both clinical care and research studies. Use of Rasch methodology for scale validation allowed for optimization of scale psychometric properties, which is particularly important when using the sum score as an overall outcome measure. Longitudinal and external validation studies are ongoing.}, } @article {pmid39877010, year = {2024}, author = {Stavrovskaya, AV and Voronkov, DN and Pavlova, AK and Olshanskiy, AS and Belugin, BV and Ivanova, MV and Zakharova, MN and Illarioshkin, SN}, title = {Intraventricular Administration of Exosomes from Patients with Amyotrophic Lateral Sclerosis Provokes Motor Neuron Disease in Mice.}, journal = {Acta naturae}, volume = {16}, number = {4}, pages = {73-80}, pmid = {39877010}, issn = {2075-8251}, abstract = {Amyotrophic lateral sclerosis (ALS) is a severe disease of the central nervous system (CNS) characterized by motor neuron damage leading to death from respiratory failure. The neurodegenerative process in ALS is characterized by an accumulation of aberrant proteins (TDP-43, SOD1, etc.) in CNS cells. The trans-synaptic transmission of these proteins via exosomes may be one of the mechanisms through which the pathology progresses. The aim of this work was to study the effect of an intraventricular injection of exosomes obtained from the cerebrospinal fluid (CSF) of ALS patients on the motor activity and CNS pathomorphology of mice. The exosomes were obtained from two ALS patients and a healthy donor. Exosome suspensions at high and low concentrations were injected into the lateral brain ventricles of male BALB/c mice (n = 45). Motor activity and physiological parameters were evaluated twice a month; morphological examination of the spinal cord was performed 14 months after the start of the experiment. Nine months after administration of exosomes from the ALS patients, the animals started exhibiting a pathological motor phenotype; i.e., altered locomotion with paresis of hind limbs, coordination impairment, and increasing episodes of immobility. The motor symptoms accelerated after administration of a higher concentration of exosomes. The experimental group showed a significant decrease in motor neuron density in the ventral horns of the spinal cord, a significant increase in the number of microglial cells, and microglia activation. The TDP43 protein in the control animals was localized in the nuclei of motor neurons. TDP43 mislocation with its accumulation in the cytoplasm was observed in the experimental group. Thus, the triggering effect of the exosomal proteins derived from the CSF of ALS patients in the development of a motor neuron pathology in the experimental animals was established. This confirms the pathogenetic role of exosomes in neurodegenerative progression and makes it possible to identify a new target for ALS therapy.}, } @article {pmid39876814, year = {2025}, author = {Papadopoulou, M and Stefanou, MI and Fanouraki, S and Moschovos, C and Bakola, E and Salakou, S and Zouvelou, V and Papadimas, GK and Tsivgoulis, G}, title = {Motor neuron diseases are not exclusively motor; the SSR paradigm.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {26}, number = {5-6}, pages = {399-408}, doi = {10.1080/21678421.2025.2458694}, pmid = {39876814}, issn = {2167-9223}, mesh = {Humans ; *Motor Neuron Disease/physiopathology/diagnosis/complications ; *Galvanic Skin Response/physiology ; *Autonomic Nervous System Diseases/diagnosis/physiopathology/etiology ; }, abstract = {Motor Neuron Diseases (MNDs), familial and sporadic, are progressive neurodegenerative disorders that, for an extended period in the past, were considered purely motor disorders. During the course of the disease, however, some patients exhibit concomitant non-motor signs; thus, MNDs are currently perceived as multisystem disorders. Assessment of non-motor symptoms is usually performed clinically, although laboratory tests can also be routinely used to objectively evaluate these symptoms. Sympathetic Skin Response (SSR) is an example of a neurophysiological test that has been used in cases of Amyotrophic Lateral Sclerosis, Spinal Muscular Atrophy, and Monomelic Atrophy, mostly to assess Autonomic Nervous System (ANS) disorders. Dysautonomia affects quality of life and life expectancy, as it is involved in cardiovascular events and incidents of sudden death. SSR abnormalities are present even in subclinical involvement of the ANS in MNDs. In this review, we present published research examining SSR findings in various MNDs, and discuss the correlation of SSR findings with clinical symptoms and disease severity, as well as the potential sources of abnormal findings. The aim of this study is to raise clinician awareness of autonomic dysfunction in MNDs and present the benefits of SSR examination in patient care.}, } @article {pmid39875596, year = {2025}, author = {Tomar, VR and Sharma, S and Siddhanta, S and Deep, S}, title = {Biophysical and spectroscopical insights into structural modulation of species in the aggregation pathway of superoxide dismutase 1.}, journal = {Communications chemistry}, volume = {8}, number = {1}, pages = {22}, pmid = {39875596}, issn = {2399-3669}, support = {CRG/2020/002091//DST | Science and Engineering Research Board (SERB)/ ; }, abstract = {Superoxide dismutase 1 (SOD1) aggregation is implicated in the development of Amyotrophic Lateral Sclerosis (ALS). Despite knowledge of the role of SOD1 aggregation, the mechanistic understanding remains elusive. Our investigation aimed to unravel the complex steps involved in SOD1 aggregation associated with ALS. Therefore, we probed the aggregation using ThT fluorescence, size-exclusion chromatography, and surface-enhanced Raman spectroscopy (SERS). The removal of metal ions and disulfide bonds resulted in the dimers rapidly first converting to an extended monomers then coming together slowly to form non-native dimers. The rapid onset of oligomerization happens above critical non-native dimer concentration. Structural features of oligomer was obtained through SERS. The kinetic data supported a fragmentation-dominant mechanism for the fibril formation. Quercetin acts as inhibitor by delaying the formation of non-native dimer and soluble oligomers by decreasing the elongation rate. Thus, results provide significant insights into the critical steps in oligomer formation and their structure.}, } @article {pmid39875548, year = {2025}, author = {Rabhi, C and Babault, N and Martin, C and Desforges, B and Maucuer, A and Joshi, V and Pankivskyi, S and Feng, Y and Bollot, G and Rattenbach, R and Pastré, D and Bouhss, A}, title = {TDP-43 nuclear retention is antagonized by hypo-phosphorylation of its C-terminus in the cytoplasm.}, journal = {Communications biology}, volume = {8}, number = {1}, pages = {136}, pmid = {39875548}, issn = {2399-3642}, support = {ANR-24-CE44-3867-01-SUFATOP//Agence Nationale de la Recherche (French National Research Agency)/ ; CIFRE Grant//Association Nationale de la Recherche et de la Technologie (National Association for Research and Technology)/ ; }, mesh = {Phosphorylation ; Humans ; *Cytoplasm/metabolism ; *DNA-Binding Proteins/metabolism/genetics/chemistry ; *Cell Nucleus/metabolism ; RNA, Messenger/metabolism/genetics ; Amyotrophic Lateral Sclerosis/metabolism ; }, abstract = {Protein aggregation is a hallmark of many neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS), in which TDP-43, a nuclear RNA-binding protein, forms cytoplasmic inclusions. Here, we have developed a robust and automated method to assess protein self-assembly in the cytoplasm using microtubules as nanoplatforms. Importantly, we have analyzed specifically the self-assembly of full-length TDP-43 and its mRNA binding that are regulated by the phosphorylation of its self-adhesive C-terminus, which is the recipient of many pathological mutations. We show that C-terminus phosphorylation prevents the recruitment of TDP-43 in mRNA-rich stress granules only under acute stress conditions because of a low affinity for mRNA but not under mild stress conditions. In addition, the self-assembly of the C-terminus is negatively regulated by phosphorylation in the cytoplasm which in turn promotes TDP-43 nuclear import. We anticipate that reducing TDP-43 C-terminus self-assembly in the cytoplasm may be an interesting strategy to reverse TDP-43 nuclear depletion in neurodegenerative diseases.}, } @article {pmid39874287, year = {2025}, author = {Baek, Y and Kim, H and Lee, D and Kim, D and Jo, E and Roh, SH and Ha, NC}, title = {Structural insights into the role of reduced cysteine residues in SOD1 amyloid filament formation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {122}, number = {5}, pages = {e2408582122}, pmid = {39874287}, issn = {1091-6490}, support = {RS-2021-IP321036//Ministry of Agriculture, Food and Rural Affairs (MAFRA)/ ; RS-2024-00344154//Ministry of Science and ICT, South Korea (MSIT)/ ; RS-2023-00245941//National Research Foundation of Korea (NRF)/ ; 2021M3A9I4021220//Ministry of Science and ICT, South Korea (MSIT)/ ; }, mesh = {*Superoxide Dismutase-1/chemistry/genetics/metabolism ; *Cysteine/chemistry/metabolism/genetics ; *Amyloid/chemistry/metabolism/genetics/ultrastructure ; Humans ; Amyotrophic Lateral Sclerosis/genetics ; Cryoelectron Microscopy ; Mutation ; }, abstract = {The formation of superoxide dismutase 1 (SOD1) filaments has been implicated in amyotrophic lateral sclerosis (ALS). Although the disulfide bond formed between Cys57 and Cys146 in the active state has been well studied, the role of the reduced cysteine residues, Cys6 and Cys111, in SOD1 filament formation remains unclear. In this study, we investigated the role of reduced cysteine residues by determining and comparing cryoelectron microscopy (cryo-EM) structures of wild-type (WT) and C6A/C111A SOD1 filaments under thiol-based reducing and metal-depriving conditions, starting with protein samples possessing enzymatic activity. The C6A/C111A mutant SOD1 formed filaments more rapidly than the WT protein. The mutant structure had a unique paired-protofilament arrangement, with a smaller filament core than that of the single-protofilament structure observed in WT SOD1. Although the single-protofilament form developed more slowly, cross-seeding experiments demonstrated the predominance of single-protofilament morphology over paired protofilaments, regardless of the presence of the Cys6 and Cys111 mutations. These findings highlight the importance of the number of amino acid residues within the filament core in determining the energy requirements for assembly. Our study provides insights into ALS pathogenesis by elucidating the initiation and propagation of filament formation, which potentially leads to deleterious amyloid filaments.}, } @article {pmid39872677, year = {2025}, author = {Pulst, SM}, title = {Spinocerebellar Ataxia Type 2: A Review and Personal Perspective.}, journal = {Neurology. Genetics}, volume = {11}, number = {1}, pages = {e200225}, pmid = {39872677}, issn = {2376-7839}, support = {R35 NS127253/NS/NINDS NIH HHS/United States ; }, abstract = {Spinocerebellar ataxias (SCAs) are dominantly inherited diseases that lead to neurodegeneration in the cerebellum and other parts of the nervous system. This review examines the progress that has been made in SCA2 from its initial clinical description to discovery of DNA CAG-repeat expansions in the ATXN2 gene. ATXN2 repeat alleles cover the range from recessive and dominant mendelian alleles to risk alleles for amyotrophic lateral sclerosis. We review studies aimed at defining the normal function of ATXN2 and mutant ATXN2 using cellular and mouse models. Progress in testing small compounds and antisense oligonucleotides in preclinical studies is described as well including our recent focus on staufen-1 (STAU1) and mRNA metabolism and control of autophagy.}, } @article {pmid39871987, year = {2024}, author = {Ribichini, E and Pallotta, N and Badiali, D and Carlucci, M and Ceccanti, M and Cambieri, C and Libonati, L and Corazziari, ES and Ruoppolo, G and Inghilleri, M}, title = {Assessment of upper GI motor activity and GI symptoms in patients with amyotrophic lateral sclerosis: an observational study.}, journal = {Frontiers in neurology}, volume = {15}, number = {}, pages = {1509917}, pmid = {39871987}, issn = {1664-2295}, abstract = {BACKGROUND/AIMS: Oro-pharyngeal dysfunction has been reported in Amyotrophic Lateral Sclerosis (ALS). We aimed to assess ALS patients upper gastrointestinal (GI) motor activity and GI symptoms according to bulbar and spinal onset and severity of ALS.

METHODS: ALS bulbar (B) and spinal (S) patients with ALS Functional Rating Scale (ALSFRS-r) ≥35, bulbar sub-score ≥10, and Forced Vital Capacity (FVC) >50%, underwent to: Fiberoptic Endoscopic Evaluation of Swallowing (FEES); esophageal manometry; gastric emptying; Rome symptom questionnaire. Medical Research Council Scale for Muscle Strength (MRC) was performed for the upper and lower limbs. Mann-Whitney's U, Fisher's ranks test, Pearson's test was used.

RESULTS: Thirteen ALS patients were included (6 F; mean age 61.2 ± 13.7 years, range: 37-87), 5 with B and 8 with S onset (ALSFRS-R score 39.5 ± 4.9, MRC score 128.6 ± 23.3, disease duration 22.8 ± 17.9 months). FEES detected a high dysphagia score in 5 patients with no difference between S and B phenotype. Lower esophageal sphincter pressure was normal in all patients. Esophageal dysmotility was observed in three S and two B onset patients. Upper esophageal sphincter (UES) pressure was higher in all ALS patients. UES spasms and delayed gastric emptying were detected in two B and one S and in two B and four S patients, respectively. There was no correlation between esophagogastric motor abnormalities and clinical characteristics of ALS, nor GI symptoms.

CONCLUSIONS: The presence of UES spasm and the delayed gastric emptying in a subgroup of ALS patients may suggest the role of ANS dysfunction in ALS.}, } @article {pmid39871563, year = {2025}, author = {Guo, J and Liu, XY and Yang, SS and Li, Q and Duan, Y and Zhu, SS and Zhou, K and Yan, YZ and Zeng, P}, title = {Roles of C/EBPβ/AEP in Neurodegenerative Diseases.}, journal = {Current topics in medicinal chemistry}, volume = {}, number = {}, pages = {}, doi = {10.2174/0115680266357822250119172351}, pmid = {39871563}, issn = {1873-4294}, abstract = {In recent years, an increasing number of studies have shown that increased activation of aspartic endopeptidases (AEPs) is a common symptom in neurodegenerative diseases (NDDs). AEP cleaves amyloid precursor protein (APP), tau (microtubule-associated protein tau), α- synuclein (α-syn), SET (a 39-KDa phosphoprotein widely expressed in various tissues and localizes predominantly in the nucleus), and TAR DNA-binding protein 43 (TDP-43), and promotes their aggregation, contributing to Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease, multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), and frontotemporal dementia (FTD) pathogenesis. Abundant evidence supports the notion that CCAAT/enhancer-binding protein β (C/EBPβ)/AEP may play an important role in NDDs. Developing its small molecule inhibitors is a promising treatment of NDDs. However, current research suggests that the pathophysiological mechanism of the C/EBPβ/AEP pathway is very complex in NDDs. This review summarizes the structure of C/EBPβ and AEP, their major physiological functions, potential pathogenesis, their small molecule inhibitors, and how C/EBPβ/AEP offers a novel pathway for the treatment of NDDs.}, } @article {pmid39871559, year = {2025}, author = {Rani, S and Tuteja, M}, title = {Chaperones as Potential Pharmacological Targets for Treating Protein Aggregation Illness.}, journal = {Current protein & peptide science}, volume = {26}, number = {6}, pages = {451-466}, pmid = {39871559}, issn = {1875-5550}, mesh = {Humans ; *Molecular Chaperones/metabolism ; Animals ; Protein Folding/drug effects ; *Neurodegenerative Diseases/metabolism/drug therapy ; Heat-Shock Proteins/metabolism ; *Protein Aggregation, Pathological/drug therapy/metabolism ; Protein Aggregates/drug effects ; Molecular Targeted Therapy ; *Proteostasis Deficiencies/drug therapy/metabolism ; }, abstract = {The three-dimensional structure of proteins, achieved through the folding of the nascent polypeptide chain in vivo, is largely facilitated by molecular chaperones, which are crucial for determining protein functionality. In addition to aiding in the folding process, chaperones target misfolded proteins for degradation, acting as a quality control system within the cell. Defective protein folding has been implicated in a wide range of clinical conditions, including neurodegenerative and metabolic disorders. It is now well understood that the pathogenesis of neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease, Huntington's disease, Amyotrophic Lateral Sclerosis, and Creutzfeldt-Jakob disease shares a common mechanism: the accumulation of misfolded proteins, which aggregate and become toxic to cells. Among the family of molecular chaperones, Heat Shock Proteins (HSPs) are highly expressed in response to cellular stress and play a pivotal role in preventing protein aggregation. Specific chaperones, particularly HSPs, are now recognized as critical in halting the accumulation and aggregation of misfolded proteins in these conditions. Consequently, these chaperones are increasingly considered promising pharmacological targets for the treatment of protein aggregation-related diseases. This review highlights research exploring the potential roles of specific molecular chaperones in disorders characterized by the accumulation of misfolded proteins.}, } @article {pmid39870504, year = {2025}, author = {Wilson, C and Giaquinto, L and Santoro, M and Di Tullio, G and Morra, V and Kukulski, W and Venditti, R and Navone, F and Borgese, N and De Matteis, MA}, title = {A role for mitochondria-ER crosstalk in amyotrophic lateral sclerosis 8 pathogenesis.}, journal = {Life science alliance}, volume = {8}, number = {4}, pages = {}, pmid = {39870504}, issn = {2575-1077}, mesh = {*Amyotrophic Lateral Sclerosis/metabolism/genetics/pathology ; *Mitochondria/metabolism ; Humans ; *Endoplasmic Reticulum/metabolism ; Motor Neurons/metabolism/pathology ; Vesicular Transport Proteins/genetics/metabolism ; Mutation ; Saccharomyces cerevisiae/metabolism/genetics ; Animals ; Protein Aggregation, Pathological ; }, abstract = {Protein aggregates in motoneurons, a pathological hallmark of amyotrophic lateral sclerosis, have been suggested to play a key pathogenetic role. ALS8, characterized by ER-associated inclusions, is caused by a heterozygous mutation in VAPB, which acts at multiple membrane contact sites between the ER and almost all other organelles. The link between protein aggregation and cellular dysfunction is unclear. A yeast model, expressing human mutant and WT-VAPB under the control of the orthologous yeast promoter in haploid and diploid cells, was developed to mimic the disease situation. Inclusion formation was found to be a developmentally regulated process linked to mitochondrial damage that could be attenuated by reducing ER-mitochondrial contacts. The co-expression of the WT protein retarded P56S-VAPB inclusion formation. Importantly, we validated these results in mammalian motoneuron cells. Our findings indicate that (age-related) damage to mitochondria influences the propensity of the mutant VAPB to form aggregates via ER-mitochondrial contacts, initiating a series of events leading to disease progression.}, } @article {pmid39870443, year = {2025}, author = {Zhang, Q and Walkley, CR}, title = {Mouse models for understanding physiological functions of ADARs.}, journal = {Methods in enzymology}, volume = {710}, number = {}, pages = {153-185}, doi = {10.1016/bs.mie.2024.11.024}, pmid = {39870443}, issn = {1557-7988}, mesh = {Animals ; *Adenosine Deaminase/genetics/metabolism ; Mice ; Humans ; *Disease Models, Animal ; RNA Editing ; Adenosine/metabolism/genetics ; Autoimmune Diseases of the Nervous System/genetics ; *RNA-Binding Proteins/genetics/metabolism ; Nervous System Malformations/genetics ; Amyotrophic Lateral Sclerosis/genetics ; Mutation ; }, abstract = {Adenosine-to-inosine (A-to-I) editing, is a highly prevalent posttranscriptional modification of RNA, mediated by the adenosine deaminases acting on RNA (ADAR) proteins. Mammalian transcriptomes contain tens of thousands to millions of A-to-I editing events. Mutations in ADAR can result in rare autoinflammatory disorders such as Aicardi-Goutières syndrome (AGS) through to irreversible conditions such as motor neuron disease, amyotrophic lateral sclerosis (ALS). Mouse models have played an important role in our current understanding of the physiology of ADAR proteins. With the advancement of genetic engineering technologies, a number of new mouse models have been recently generated, each providing additional insight into ADAR function. This review highlights both past and current mouse models, exploring the methodologies used in their generation, their respective discoveries, and the significance of these findings in relation to human ADAR physiology.}, } @article {pmid39868844, year = {2025}, author = {Elyaman, W and Stern, LJ and Jiang, N and Dressman, D and Bradley, P and Klatzmann, D and Bradshaw, EM and Farber, DL and Kent, SC and Chizari, S and Funk, K and Devanand, D and Thakur, KT and Raj, T and Dalahmah, OA and Sarkis, RA and Weiner, HL and Shneider, NA and Przedborski, S}, title = {Exploring the role of T cells in Alzheimer's and other neurodegenerative diseases: Emerging therapeutic insights from the T Cells in the Brain symposium.}, journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association}, volume = {21}, number = {2}, pages = {e14548}, pmid = {39868844}, issn = {1552-5279}, support = {T32 AI148099/AI/NIAID NIH HHS/United States ; P01 AI106697/AI/NIAID NIH HHS/United States ; R01AI137198/NH/NIH HHS/United States ; R13 AG090018/AG/NIA NIH HHS/United States ; R01 AG067581/AG/NIA NIH HHS/United States ; R01 AG076018/AG/NIA NIH HHS/United States ; R35 GM141457/GM/NIGMS NIH HHS/United States ; P30 AG066514/AG/NIA NIH HHS/United States ; T32AI148099-4/NH/NIH HHS/United States ; AI106697/NH/NIH HHS/United States ; R01 AG055422/AG/NIA NIH HHS/United States ; R01AG067581/NH/NIH HHS/United States ; R13AG090018-01/NH/NIH HHS/United States ; R01AG076018/NH/NIH HHS/United States ; AG R01AG055422/NH/NIH HHS/United States ; R35GM141457/NH/NIH HHS/United States ; R01 AI137198/AI/NIAID NIH HHS/United States ; }, mesh = {Humans ; *Alzheimer Disease/immunology/therapy ; *Brain/immunology ; Immunotherapy ; *Neurodegenerative Diseases/immunology/therapy ; *T-Lymphocytes/immunology ; }, abstract = {This proceedings article summarizes the inaugural "T Cells in the Brain" symposium held at Columbia University. Experts gathered to explore the role of T cells in neurodegenerative diseases. Key topics included characterization of antigen-specific immune responses, T cell receptor (TCR) repertoire, microbial etiology in Alzheimer's disease (AD), and microglia-T cell crosstalk, with a focus on how T cells affect neuroinflammation and AD biomarkers like amyloid beta and tau. The symposium also examined immunotherapies for AD, including the Valacyclovir Treatment of Alzheimer's Disease (VALAD) trial, and two clinical trials leveraging regulatory T cell approaches for multiple sclerosis and amyotrophic lateral sclerosis therapy. Additionally, single-cell RNA/TCR sequencing of T cells and other immune cells provided insights into immune dynamics in neurodegenerative diseases. This article highlights key findings from the symposium and outlines future research directions to further understand the role of T cells in neurodegeneration, offering innovative therapeutic approaches for AD and other neurodegenerative diseases. HIGHLIGHTS: Researchers gathered to discuss approaches to study T cells in brain disorders. New technologies allow high-throughput screening of antigen-specific T cells. Microbial infections can precede several serious and chronic neurological diseases. Central and peripheral T cell responses shape neurological disease pathology. Immunotherapy can induce regulatory T cell responses in neuroinflammatory disorders.}, } @article {pmid39867453, year = {2024}, author = {Rong, P and Heidrick, L and Pattee, G}, title = {A novel muscle network approach for objective assessment and profiling of bulbar involvement in ALS.}, journal = {Frontiers in neuroscience}, volume = {18}, number = {}, pages = {1491997}, pmid = {39867453}, issn = {1662-4548}, abstract = {INTRODUCTION: As a hallmark feature of amyotrophic lateral sclerosis (ALS), bulbar involvement significantly impacts psychosocial, emotional, and physical health. A validated objective marker is however lacking to characterize and phenotype bulbar involvement, positing a major barrier to early detection, progress monitoring, and tailored care. This study aimed to bridge this gap by constructing a multiplex functional mandibular muscle network to provide a novel objective measurement tool of bulbar involvement.

METHODS: A noninvasive electrophysiological technique-surface electromyography-was combined with graph network analysis to extract 48 features measuring the regulatory mechanisms, connectivity, integration, segregation, assortativity, and lateralization of the functional muscle network during a speech task. These features were clustered into 10 interpretable latent factors. To evaluate the utility of the muscle network as a bulbar measurement tool, a heterogenous ALS cohort, consisting of eight individuals with overt clinical bulbar symptoms and seven without, along with 10 neurologically healthy controls, was employed to train and validate statistical and machine learning algorithms to assess the disease effects on the network features and the relation of the network performance to the current clinical diagnostic standard and behavioral patterns of bulbar involvement.

RESULTS: Significant disease effects were found on most network features. The most robust effects were manifested by reduced and more variable myoelectric activities, and reduced functional connectivity and integration of the muscle network. The 10 latent factors (1) demonstrated acceptably high efficacy for detecting bulbar neuromuscular changes across all clinically confirmed symptomatic cases and clinically silent prodromal cases (area under the curve = 0.89-0.91; F1 score = 0.85-0.87; precision = 0.84-0.86; recall = 0.87-0.88); and (2) selectively correlated with clinically meaningful behavioral patterns (conditional R [2] = 0.45-0.81).

CONCLUSION: The functional muscle network shows promise for an objective quantifiable measurement tool to improve early detection and profiling of bulbar involvement across the prodromal and symptomatic stages. This tool has various strengths, including the use of a clinically readily available noninvasive instrument, fully automated data processing and analytics, and generation of interpretable objective outcome measures (i.e., latent factors), together rendering it highly scalable in routine clinical practice for assessing and monitoring of bulbar involvement.}, } @article {pmid39866212, year = {2025}, author = {Wang, W and Cooper, C}, title = {Metabolic dysfunction-associated steatotic liver disease and type 2 diabetes: A dual threat to cardiac dysfunction progression.}, journal = {World journal of cardiology}, volume = {17}, number = {1}, pages = {102467}, pmid = {39866212}, issn = {1949-8462}, abstract = {Metabolic dysfunction-associated steatotic liver disease (MASLD), particularly in patients with type 2 diabetes mellitus (T2DM), is increasingly recognized as a multi-system disease that affects both hepatic and cardiovascular health. This study explores the association between MASLD-related liver fibrosis and cardiac dysfunction, focusing on how liver fibrosis contributes to cardiac remodeling and dysfunction. Cernea et al's research highlights the strong correlation between liver fibrosis and changes in left ventricular mass, left atrial dimensions, and systolic and diastolic function in diabetic patients. Notably, the study suggests a protective role of sex-hormone binding protein against cardiac remodeling. These findings underline the importance of early detection of liver fibrosis using non-invasive markers like fibrosis-4 index and nonalcoholic fatty liver disease fibrosis scores, which may offer dual protection for both liver and heart health in T2DM patients. Moreover, this study calls for further research into the shared pathogenic mechanisms, including inflammation and fibrosis pathways, between the liver and heart. It advocates for the integration of liver fibrosis screening into cardiovascular risk management, urging clinicians to adopt a more holistic approach in treating patients with MASLD and T2DM. The research has broad implications for preventing cardiovascular complications and improving outcomes in this high-risk population.}, } @article {pmid39865792, year = {2025}, author = {Murakami, E and Shibata, T and Tomemori, M and Kawai, G and Nakatani, K}, title = {The role of spatial arrangement of aromatic rings on the binding of N,N'-diheteroaryl guanidine ligands to the G2C4/G2C4 motif DNA.}, journal = {Physical chemistry chemical physics : PCCP}, volume = {27}, number = {6}, pages = {3341-3350}, doi = {10.1039/d4cp03213f}, pmid = {39865792}, issn = {1463-9084}, mesh = {*DNA/chemistry/metabolism ; Ligands ; Surface Plasmon Resonance ; *Guanidine/chemistry/analogs & derivatives ; Circular Dichroism ; Hydrogen Bonding ; Humans ; }, abstract = {Non-canonical DNA structures formed by aberrantly expanded repeat DNA are implicated in promoting repeat instability and the onset of repeat expansion diseases. Small molecules that target these disease-causing repeat DNAs hold promise as therapeutic agents for such diseases. Specifically, 1,3-di(quinolin-2-yl)guanidine (DQG) has been identified to bind to the disease-causing GGCCCC (G2C4) repeat DNA associated with amyotrophic lateral sclerosis and frontotemporal dementia (ALS/FTD). In this study, we investigate the structure-binding relationships between DQG analogs and double-stranded DNA (dsDNA) containing a G2C4/G2C4 unit. Our findings, derived from UV melting temperature, circular dichroism spectra, and surface plasmon resonance (SPR) analyses of DQG analogs, highlight the crucial role of the spatial arrangements of aromatic rings in binding to the G2C4/G2C4 unit. Among the tested DQG analogs, N,N'-di(quinazolin-2-yl)guanidine (DQzG) stands out for its ability to form seven planar conformers. These conformers enable ADD-DAA hydrogen bonding with cytosine and multiple spatial arrangements of aromatic rings, including those resembling DQG. Our binding analyses revealed that DQzG exhibits the highest affinity binding for the G2C4/G2C4 unit. NMR analysis of the DQzG-bound G2C4/G2C4-dsDNA further suggested that DQzG binds to the G2C4/G2C4 unit via hydrogen bonding. Moreover, SPR analysis demonstrated that DQzG binds more strongly to G2C4 repeat DNA compared to DQG. These results position DQzG as a promising lead compound for targeting the G2C4 repeat, offering potential therapeutic avenues for the treatment of ALS/FTD and other repeat expansion diseases.}, } @article {pmid39865616, year = {2025}, author = {Dong, S and Liu, X and Zhou, Y and Li, J and Qi, Z and Wang, Z and Yang, W and Chen, X}, title = {Prognostic Value of Cerebrospinal Fluid and Serum Neurofilament Light Chain in Amyotrophic Lateral Sclerosis: A Correlation Study.}, journal = {Brain and behavior}, volume = {15}, number = {1}, pages = {e70256}, pmid = {39865616}, issn = {2162-3279}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/blood/cerebrospinal fluid/diagnosis ; *Neurofilament Proteins/blood/cerebrospinal fluid ; Male ; Female ; Middle Aged ; Prognosis ; Aged ; Biomarkers/blood/cerebrospinal fluid ; Disease Progression ; Adult ; }, abstract = {BACKGROUND: The diagnostic and prognostic values of serum neurofilament light chain (sNfL), in comparison to cerebrospinal fluid (CSF) neurofilament light chain (cNfL), and other clinical parameters in amyotrophic lateral sclerosis (ALS) at the time of diagnosis remain elusive.

METHODS: We examine paired serum and CSF samples from 80 ALS patients and 21 control subjects, all obtained at the time of diagnosis. Additional serum samples were collected from 51 other ALS patients. NfL concentrations were quantified using the single molecule array (Simoa) technique.

RESULTS: Our findings demonstrate a robust correlation between NfL levels in matched CSF and serum samples. Notably, both sNfL (p < 0.0001) and cNfL (p < 0.0001) exhibited significantly elevated levels in ALS patients compared to controls. Furthermore, baseline sNfL concentrations, as well as cNfL levels, emerged as predictive indicators of subsequent disease progression rate (sNfL: p < 0.0001, cNfL: p = 0.0005) and overall survival (sNfL: p = 0.0073, cNfL: p = 0.0044). Employing a Cox regression model, we identified baseline sNfL level (HR = 1.01, p = 0.013), and diagnostic delay (HR = 0.94, p = 0.003) as independent prognostic factors for mortality. Furthermore, we constructed a nomogram model that incorporates both sNfL and pertinent clinical variables, which substantially enhances the accuracy of predicting disease outcomes (Concordance Index, 0.808).

CONCLUSION: Our study underscores the robust correlation between sNfL and cNfL in ALS patients and establishes baseline sNfL as a potent and independent prognostic marker for mortality.}, } @article {pmid39863573, year = {2025}, author = {Ting, HC and Guo, YT and Su, HL and Chen, YS and Lin, SZ and Harn, HJ and Chang, CY}, title = {Rapid iPSC-derived neuromuscular junction model uncovers motor neuron dominance in amyotrophic lateral sclerosis cytopathy.}, journal = {Cell death discovery}, volume = {11}, number = {1}, pages = {23}, pmid = {39863573}, issn = {2058-7716}, abstract = {The neuromuscular junction (NMJ) is essential for transmitting signals from motor neurons (MNs) to skeletal muscles (SKMs), and its dysfunction can lead to severe motor disorders. However, our understanding of the NMJ is limited by the absence of accurate human models. Although human induced pluripotent stem cell (iPSC)-derived models have advanced NMJ research, their application is constrained by challenges such as limited differentiation efficiency, lengthy generation times, and cryopreservation difficulties. To overcome these limitations, we developed a rapid human NMJ model using cryopreserved MNs and SKMs derived from iPSCs. Within 12 days of coculture, we successfully recreated NMJ-specific connectivity that closely mirrors in vivo synapse formation. Using this model, we investigated amyotrophic lateral sclerosis (ALS) and replicated ALS-specific NMJ cytopathies with SOD1 mutant and corrected isogenic iPSC lines. Quantitative analysis of 3D confocal microscopy images revealed a critical role of MNs in initiating ALS-related NMJ cytopathies, characterized by alterations in the volume, number, intensity, and distribution of acetylcholine receptors, ultimately leading to impaired muscle contractions. Our rapid and precise in vitro NMJ model offers significant potential for advancing research on NMJ physiology and pathology, as well as for developing treatments for NMJ-related diseases.}, } @article {pmid39863163, year = {2025}, author = {Kearney, CA and Needle, CD and Brinks, AL and Gutierrez, D and Lo Sicco, KI}, title = {Response to Sood et al's "Systemic Janus kinase inhibitor treatment for vitiligo: An evidence-based review".}, journal = {Journal of the American Academy of Dermatology}, volume = {92}, number = {5}, pages = {e155-e156}, doi = {10.1016/j.jaad.2025.01.059}, pmid = {39863163}, issn = {1097-6787}, } @article {pmid39863029, year = {2025}, author = {Liu, X and Li, T and Tu, X and Xu, M and Wang, J}, title = {Mitochondrial fission and fusion in neurodegenerative diseases:Ca[2+] signalling.}, journal = {Molecular and cellular neurosciences}, volume = {132}, number = {}, pages = {103992}, doi = {10.1016/j.mcn.2025.103992}, pmid = {39863029}, issn = {1095-9327}, mesh = {Humans ; *Mitochondrial Dynamics/physiology ; *Neurodegenerative Diseases/metabolism/pathology ; *Calcium Signaling ; Animals ; *Mitochondria/metabolism ; Mitochondrial Proteins/metabolism ; }, abstract = {Neurodegenerative diseases (NDs) are a group of disorders characterized by the progressive loss of neuronal structure and function. The pathogenesis is intricate and involves a network of interactions among multiple causes and systems. Mitochondria and Ca[2+] signaling have long been considered to play important roles in the development of various NDs. Mitochondrial fission and fusion dynamics are important processes of mitochondrial quality control, ensuring the stability of mitochondrial structure and function. Mitochondrial fission and fusion imbalance and Ca[2+] signaling disorders can aggravate the disease progression of NDs. In this review, we explore the relationship between mitochondrial dynamics and Ca[2+] signaling in AD, PD, ALS, and HD, focusing on the roles of key regulatory proteins (Drp1, Fis1, Mfn1/2, and Opa1) and the association structures between mitochondria and the endoplasmic reticulum (MERCs/MAMs). We provide a detailed analysis of their involvement in the pathogenesis of these four NDs. By integrating these mechanisms, we aim to clarify their contributions to disease progression and offer insights into the development of therapeutic strategies that target mitochondrial dynamics and Ca[2+] signaling. We also examine the progress in drug research targeting these pathways, highlighting their potential as therapeutic targets in the treatment of NDs.}, } @article {pmid39862884, year = {2025}, author = {Moens, TG and Da Cruz, S and Neumann, M and Shelkovnikova, TA and Shneider, NA and Van Den Bosch, L}, title = {Amyotrophic lateral sclerosis caused by FUS mutations: advances with broad implications.}, journal = {The Lancet. Neurology}, volume = {24}, number = {2}, pages = {166-178}, doi = {10.1016/S1474-4422(24)00517-9}, pmid = {39862884}, issn = {1474-4465}, support = {SHELKOVNIKOVA/OCT17/968-799/MNDA_/Motor Neurone Disease Association/United Kingdom ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/therapy/pathology ; *RNA-Binding Protein FUS/genetics ; *Mutation/genetics ; Animals ; }, abstract = {Autosomal dominant mutations in the gene encoding the DNA and RNA binding protein FUS are a cause of amyotrophic lateral sclerosis (ALS), and about 0·3-0·9% of patients with ALS are FUS mutation carriers. FUS-mutation-associated ALS (FUS-ALS) is characterised by early onset and rapid progression, compared with other forms of ALS. However, different pathogenic mutations in FUS can result in markedly different age at symptom onset and rate of disease progression. Most FUS mutations disrupt its nuclear localisation, leading to its cytoplasmic accumulation in the CNS. FUS also forms inclusions in around 5% of patients with the related neurodegenerative condition frontotemporal dementia. However, there are key differences between the two diseases at the genetic and neuropathological level, which suggest distinct pathogenic processes. Experimental models have uncovered potential pathogenic mechanisms in FUS-ALS and informed therapeutic strategies that are currently in development, including the silencing of FUS expression using an intrathecally administered antisense oligonucleotide.}, } @article {pmid39862877, year = {2025}, author = {Feldman, EL and Sattler, R and Kiernan, MC and Goutman, SA and Chiò, A and Al-Chalabi, A}, title = {Transforming amyotrophic lateral sclerosis into a liveable disease.}, journal = {The Lancet. Neurology}, volume = {24}, number = {2}, pages = {100-101}, doi = {10.1016/S1474-4422(24)00523-4}, pmid = {39862877}, issn = {1474-4465}, } @article {pmid39861520, year = {2025}, author = {Tripolskaja, L and Kazlauskaite-Jadzevice, A and Razukas, A and Baksiene, E}, title = {Perennial Grasses on Stony Sandy Loam Arenosol: Summary of Results of Long-Term Experiment in Northern Europe Region (1995-2024).}, journal = {Plants (Basel, Switzerland)}, volume = {14}, number = {2}, pages = {}, pmid = {39861520}, issn = {2223-7747}, support = {"Improvement of the preparation of highly skilled professionals for development of science-intensive economic entities-NKPDOKT" (project code No: VP1-3.1-ŠMM-01-V-03-001)//Lietuvos mokslų taryba/ ; }, abstract = {Grasses can sustain soil functions despite nutrient depletion, which can have serious consequences for soil processes and ecosystem services. This paper summarizes the results of the long-term experiment (1995-2024) carried out in Arenosol within a temperate climate zone, focusing on the productivity of natural and managed grasslands; their succession changes over time, and so do the effects on soil chemical properties, and soil organic carbon (SOC) sequestration. The results indicated that two land uses-abandoned land (AL) and grassland fertilized with mineral fertilizers (MGf)-can be effectively applied to prevent Arenosol soil degradation. SOC accumulation occurs more rapidly in AL soils, and their chemical properties show less change over time. The ability of grasses to sequester SOC is better reflected by SOC stocks across the Ah horizon, where thickness varies over long-term grassland use. Significant changes in soil properties were observed more than 20 years after converting arable to herbaceous land use. While MGf has the highest biomass productivity, the use of fertilizers leads to soil acidification. The biomass productivity of AL and MGf increased with longer grassland use; however, in MG, productivity decreased without fertilizers, reaching AL's productivity levels after 20 years. As the age of AL increased, plant biodiversity decreased, and drought-resistant plants began to spread.}, } @article {pmid39860557, year = {2025}, author = {Chmiel, J and Stępień-Słodkowska, M}, title = {Resting-State EEG Oscillations in Amyotrophic Lateral Sclerosis (ALS): Toward Mechanistic Insights and Clinical Markers.}, journal = {Journal of clinical medicine}, volume = {14}, number = {2}, pages = {}, pmid = {39860557}, issn = {2077-0383}, abstract = {Introduction: Amyotrophic lateral sclerosis (ALS) is a complex, progressive neurodegenerative disorder characterized by the degeneration of motor neurons in the brain, brainstem, and spinal cord. Several neuroimaging techniques can help reveal the pathophysiology of ALS. One of these is the electroencephalogram (EEG), a noninvasive and relatively inexpensive tool for examining electrical activity of the brain with excellent temporal precision. Methods: This mechanistic review examines the pattern of resting-state EEG activity. With a focus on publications published between January 1995 and October 2024, we carried out a comprehensive search in October 2024 across a number of databases, including PubMed/Medline, Research Gate, Google Scholar, and Cochrane. Results: The literature search yielded 17 studies included in this review. The studies varied significantly in their methodology and patient characteristics. Despite this, a common biomarker typical of ALS was found-reduced alpha power. Regarding other oscillations, the findings are less consistent and sometimes contradictory. As this is a mechanistic review, three possible explanations for this biomarker are provided. The main and most important one is increased cortical excitability. In addition, due to the limitations of the studies, recommendations for future research on this topic are outlined to enable a further and better understanding of EEG patterns in ALS. Conclusions: Most studies included in this review showed alpha power deficits in ALS patients, reflecting pathological hyperexcitability of the cerebral cortex. Future studies should address the methodological limitations identified in this review, including small sample sizes, inconsistent frequency-band definitions, and insufficient functional outcome measures, to solidify and extend current findings.}, } @article {pmid39859339, year = {2025}, author = {Yashooa, RK and Duranti, E and Conconi, D and Lavitrano, M and Mustafa, SA and Villa, C}, title = {Mitochondrial microRNAs: Key Drivers in Unraveling Neurodegenerative Diseases.}, journal = {International journal of molecular sciences}, volume = {26}, number = {2}, pages = {}, pmid = {39859339}, issn = {1422-0067}, mesh = {Humans ; *MicroRNAs/genetics/metabolism ; *Mitochondria/genetics/metabolism ; *Neurodegenerative Diseases/genetics/metabolism/pathology ; Animals ; Gene Expression Regulation ; Parkinson Disease/genetics/metabolism ; DNA, Mitochondrial/genetics ; }, abstract = {MicroRNAs (miRNAs) are a class of small non-coding RNAs (ncRNAs) crucial for regulating gene expression at the post-transcriptional level. Recent evidence has shown that miRNAs are also found in mitochondria, organelles that produce energy in the cell. These mitochondrial miRNAs, also known as mitomiRs, are essential for regulating mitochondrial function and metabolism. MitomiRs can originate from the nucleus, following traditional miRNA biogenesis pathways, or potentially from mitochondrial DNA, allowing them to directly affect gene expression and cellular energy dynamics within the mitochondrion. While miRNAs have been extensively investigated, the function and involvement of mitomiRs in the development of neurodegenerative disorders like Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis remain to be elucidated. This review aims to discuss findings on the role of mitomiRs in such diseases and their potential as therapeutic targets, as well as to highlight future research directions.}, } @article {pmid39859258, year = {2025}, author = {Szablewski, L}, title = {Associations Between Diabetes Mellitus and Neurodegenerative Diseases.}, journal = {International journal of molecular sciences}, volume = {26}, number = {2}, pages = {}, pmid = {39859258}, issn = {1422-0067}, mesh = {Humans ; *Neurodegenerative Diseases/metabolism/etiology/complications/pathology ; *Diabetes Mellitus, Type 2/complications/metabolism ; Oxidative Stress ; Animals ; Parkinson Disease ; Huntington Disease ; *Diabetes Mellitus, Type 1/complications/metabolism ; Alzheimer Disease/metabolism ; Amyotrophic Lateral Sclerosis ; *Diabetes Mellitus/metabolism ; }, abstract = {Diabetes mellitus (DM) and neurodegenerative diseases/disturbances are worldwide health problems. The most common chronic conditions diagnosed in persons 60 years and older are type 2 diabetes mellitus (T2DM) and cognitive impairment. It was found that diabetes mellitus is a major risk for cognitive decline, dementia, Parkinson's disease (PD), Alzheimer's disease (AD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS) and other neurodegenerative disorders. Different mechanisms of associations between these diseases and diabetes mellitus have been suggested. For example, it is postulated that an impaired intracellular insulin signaling pathway, together with hyperglycemia and hyperinsulinemia, may cause pathological changes, such as dysfunction of the mitochondria, oxidative stress inflammatory responses, etc. The association between diabetes mellitus and neurodegenerative diseases, as well as the mechanisms of these associations, needs further investigation. The aim of this review is to describe the associations between diabetes mellitus, especially type 1 (T1DM) and type 2 diabetes mellitus, and selected neurodegenerative diseases, i.e., Alzheimer's disease, Parkinson's disease, Huntington's disease and amyotrophic lateral sclerosis. Suggested mechanisms of these associations are also described.}, } @article {pmid39858428, year = {2024}, author = {Argueti-Ostrovsky, S and Barel, S and Kahn, J and Israelson, A}, title = {VDAC1: A Key Player in the Mitochondrial Landscape of Neurodegeneration.}, journal = {Biomolecules}, volume = {15}, number = {1}, pages = {}, pmid = {39858428}, issn = {2218-273X}, support = {#284/19 and #485/24//Israel Science Foundation/ ; }, mesh = {Humans ; *Voltage-Dependent Anion Channel 1/metabolism/genetics ; *Mitochondria/metabolism/pathology ; *Neurodegenerative Diseases/metabolism/pathology ; Animals ; alpha-Synuclein/metabolism/genetics ; Amyloid beta-Peptides/metabolism ; Superoxide Dismutase-1/metabolism/genetics ; Oxidative Stress ; }, abstract = {Voltage-Dependent Anion Channel 1 (VDAC1) is a mitochondrial outer membrane protein that plays a crucial role in regulating cellular energy metabolism and apoptosis by mediating the exchange of ions and metabolites between mitochondria and the cytosol. Mitochondrial dysfunction and oxidative stress are central features of neurodegenerative diseases. The pivotal functions of VDAC1 in controlling mitochondrial membrane permeability, regulating calcium balance, and facilitating programmed cell death pathways, position it as a key determinant in the delicate balance between neuronal viability and degeneration. Accordingly, increasing evidence suggests that VDAC1 is implicated in the pathophysiology of neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and others. This review summarizes the current findings on the contribution of VDAC1 to neurodegeneration, focusing on its interactions with disease-specific proteins, such as amyloid-β, α-synuclein, and mutant SOD1. By unraveling the complex involvement of VDAC1 in neurodegenerative processes, this review highlights potential avenues for future research and drug development aimed at alleviating mitochondrial-related neurodegeneration.}, } @article {pmid39857761, year = {2025}, author = {Sun, C and Chen, Y and Xu, L and Wang, W and Zhang, N and Fournier, CN and Li, N and Fan, D}, title = {Rasch-Built Overall Amyotrophic Lateral Sclerosis Disability Scale as a Novel Tool to Measure Disease Progression.}, journal = {Biomedicines}, volume = {13}, number = {1}, pages = {}, pmid = {39857761}, issn = {2227-9059}, support = {82001347//National Natural Science Foundation of China/ ; 82071426//National Natural Science Foundation of China/ ; 81701067//National Natural Science Foundation of China/ ; BYSYDL2019002//Clinical Cohort Construction Program of Peking University Third Hospital/ ; }, abstract = {Background: A valuable outcome measure to monitor amyotrophic lateral sclerosis (ALS) disease progression is crucial in clinical trials. Rasch-Built Overall Amyotrophic Lateral Sclerosis Disability Scale (ROADS) is a novel questionnaire assessing ALS disability. Currently, there are no studies on the relationship between ROADS and ALS survival. This study explored the value of Chinese ROADS as a novel tool for measuring disease progression and the correlation between ROADS and ALS survival. Methods: A total of 170 ALS participants were included in this study. Clinical characteristics and baseline ROADS, ΔROADS, ALSFRS-R, and ΔFRS of patients were collected. Participants were followed for 18 months to assess time to tracheostomy and survival. Scales were collected every 3 to 6 months. We evaluated the association of baseline ROADS and ΔROADS with survival using Cox regression analyses. Linear mixed effects models were used to assess changes over time in ROADS and ALSFRS-R. Results: Multivariate Cox models confirmed that baseline ROADS positively correlated with ALS survival (HR = 0.95, p < 0.001), while baseline ΔROADS negatively correlated with survival (HR = 1.26, p < 0.001). Additionally, linear mixed effects models suggested that ROADS, similar to ALSFRS-R, declined significantly over time, but there was no significant difference between these two. Conclusions: Our study indicates that Chinese ROADS is strongly related to ALS survival. Changes in ROADS with disease progression are similar to those in ALSFRS-R. These findings support Chinese ROADS as a reliable outcome measure for clinical trials, potentially enhancing the dimension of evaluating treatment effectiveness in ALS trials.}, } @article {pmid39857633, year = {2024}, author = {Zhang, G and Cao, W and Wang, Z and Xia, K and Deng, B and Fan, D}, title = {Associations of Abnormal Sleep Duration and Chronotype with Higher Risk of Incident Amyotrophic Lateral Sclerosis: A UK Biobank Prospective Cohort Study.}, journal = {Biomedicines}, volume = {13}, number = {1}, pages = {}, pmid = {39857633}, issn = {2227-9059}, support = {82301601 81873784 82071426//National Natural Science Foundation of China/ ; }, abstract = {Background: The occurrence of sleep disturbances in amyotrophic lateral sclerosis (ALS) patients is widely reported. However, there is still a lack of reliable evidence of a relationship between sleep disturbances and the risk of developing ALS. The aim of this study was to prospectively investigate the longitudinal associations between sleep traits and the risk of incident ALS. Methods: We included information from 409,045 individuals from the prospective cohort of the UK Biobank. Sleep traits at baseline were measured using a standardized questionnaire. All sleep traits were analyzed in relation to the subsequent incidence of ALS using Cox proportional hazards models. Results: Multivariate analysis showed that 6-7 h of sleep was related to the lowest risk for ALS. A long sleep duration (≥8 h) was associated with an increased risk of ALS incidence (HR: 1.31, 95% CI: 1.07-1.61; p = 0.009). A short sleep duration (<6 h) was associated with an increased risk of ALS incidence (HR: 1.91, 95% CI: 1.10-3.30, p = 0.021) in females. In participants aged ≥65 years, eveningness was associated with increased ALS risk (HR: 1.32, 95% CI: 1.08-1.61; p = 0.006). Conclusion: Our results hint at a sleep duration that is too short or too long, and certain chronotypes might be related to the risk of developing ALS. Despite the limitations imposed by the study design and the subjectivity of sleep information, our findings suggest that sleep disturbances may influence the risk of developing ALS.}, } @article {pmid39857620, year = {2024}, author = {Frawley, L and Taylor, NT and Sivills, O and McPhillamy, E and To, TD and Wu, Y and Chin, BY and Wong, CY}, title = {Stem Cell Therapy for the Treatment of Amyotrophic Lateral Sclerosis: Comparison of the Efficacy of Mesenchymal Stem Cells, Neural Stem Cells, and Induced Pluripotent Stem Cells.}, journal = {Biomedicines}, volume = {13}, number = {1}, pages = {}, pmid = {39857620}, issn = {2227-9059}, support = {Australian Government New Colombo Plan (NCP) scheme//Australian Government New Colombo Plan (NCP) scheme/ ; }, abstract = {BACKGROUND/OBJECTIVES: Amyotrophic lateral sclerosis (ALS), or Lou Gehrig's disease, is a debilitating, incurable neurodegenerative disorder characterised by motor neuron death in the spinal cord, brainstem, and motor cortex. With an incidence rate of about 4.42 cases per 100,000 people annually, ALS severely impacts motor function and quality of life, causing progressive muscle atrophy, spasticity, paralysis, and eventually death. The cause of ALS is largely unknown, with 90% of cases being sporadic and 10% familial. Current research targets molecular mechanisms of inflammation, excitotoxicity, aggregation-prone proteins, and proteinopathy.

METHODS: This review evaluates the efficacy of three stem cell types in ALS treatment: mesenchymal stem cells (MSCs), neural stem cells (NSCs), and induced pluripotent stem cells (iPSCs).

RESULTS: MSCs, derived from various tissues, show neuroprotective and regenerative qualities, with clinical trials suggesting potential benefits but limited by small sample sizes and non-randomised designs. NSCs, isolated from the fetal spinal cord or brain, demonstrate promise in animal models but face functional integration and ethical challenges. iPSCs, created by reprogramming patient-specific somatic cells, offer a novel approach by potentially replacing or supporting neurons. iPSC therapy addresses ethical issues related to embryonic stem cells but encounters challenges regarding genotoxicity and epigenetic irregularities, somatic cell sources, privacy concerns, the need for extensive clinical trials, and high reprogramming costs.

CONCLUSIONS: This research is significant for advancing ALS treatment beyond symptomatic relief and modest survival extensions to actively modifying disease progression and improving patient outcomes. Successful stem cell therapies could lead to new ALS treatments, slowing motor function loss and reducing symptom severity.}, } @article {pmid39857328, year = {2025}, author = {Stoccoro, A}, title = {Epigenetic Mechanisms Underlying Sex Differences in Neurodegenerative Diseases.}, journal = {Biology}, volume = {14}, number = {1}, pages = {}, pmid = {39857328}, issn = {2079-7737}, support = {GR-2021-12374436//Italian Ministry of Health, Ricerca Finalizzata/ ; }, abstract = {Neurodegenerative diseases are characterized by profound differences between females and males in terms of incidence, clinical presentation, and disease progression. Furthermore, there is evidence suggesting that differences in sensitivity to medical treatments may exist between the two sexes. Although the role of sex hormones and sex chromosomes in driving differential susceptibility to these diseases is well-established, the molecular alterations underlying these differences remain poorly understood. Epigenetic mechanisms, including DNA methylation, histone tail modifications, and the activity of non-coding RNAs, are strongly implicated in the pathogenesis of neurodegenerative diseases. While it is known that epigenetic mechanisms play a crucial role in sexual differentiation and that distinct epigenetic patterns characterize females and males, sex-specific epigenetic patterns have been largely overlooked in studies aiming to identify epigenetic alterations associated with neurodegenerative diseases. This review aims to provide an overview of sex differences in epigenetic mechanisms, the role of sex-specific epigenetic processes in the central nervous system, and the main evidence of sex-specific epigenetic alterations in three neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. Understanding the sex-related differences of these diseases is essential for developing personalized treatments and interventions that account for the unique epigenetic landscapes of each sex.}, } @article {pmid39855275, year = {2025}, author = {Zhang, W and Zhang, L and Fu, S and Yan, R and Zhang, X and Song, J and Lu, Y}, title = {Roles of NLRC4 inflammasome in neurological disorders: Mechanisms, implications, and therapeutic potential.}, journal = {Pharmacology & therapeutics}, volume = {267}, number = {}, pages = {108803}, doi = {10.1016/j.pharmthera.2025.108803}, pmid = {39855275}, issn = {1879-016X}, mesh = {Humans ; *Inflammasomes/metabolism/immunology ; Animals ; *Calcium-Binding Proteins/metabolism ; *Nervous System Diseases/drug therapy/immunology/metabolism ; *CARD Signaling Adaptor Proteins/metabolism ; *Apoptosis Regulatory Proteins/metabolism ; Neurodegenerative Diseases/drug therapy/immunology ; }, abstract = {The nucleotide-binding oligomerization domain-like receptor family caspase recruitment domain containing 4 (NLRC4) inflammasome, a vital component of the innate immune system, is known for defending against bacterial infections. However, recent insights have revealed its significant impact on neurological disorders. This comprehensive review discussed the mechanisms underlying the activation and regulation of the NLRC4 inflammasome, highlighting the complexity of its response to cellular stress and damage signals. The biological functions of NLRC4 were explored, particularly its influence on cytokine production and the induction of pyroptosis, a form of inflammatory cell death. This review further emphasized the role of the NLRC4 inflammasome in brain injuries and neurodegenerative disorders. In the realm of brain injuries such as stroke and traumatic brain injury, as well as in neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, multiple sclerosis, and amyotrophic lateral sclerosis, the NLRC4 inflammasome played a pivotal role in modulating neuroinflammatory responses, which was crucial for understanding the progression and potential therapeutic targeting of these conditions. The emerging role of NLRC4 in psychiatric disorders and its potential impact on glioma progression were also examined. Additionally, this review presented a thorough summary of the latest research on inhibitors that impeded the assembly and activation of the NLRC4 inflammasome, pointing to new therapeutic possibilities in neurological disorders. In conclusion, by integrating current knowledge on the activation and regulation of NLRC4 with its biological functions and clinical implications, this article underscored the importance of NLRC4 inflammasome in neurological pathologies, which opened new possibilities for the treatment of challenging neurological conditions.}, } @article {pmid39854930, year = {2025}, author = {Drouet, C and Priou, P and Gagnadoux, F and Trzepizur, W}, title = {Constraints to the initiation of home non-invasive ventilation and short-term efficacy in different diagnostic groups (as a prelude to an ambulatory shift).}, journal = {Respiratory medicine and research}, volume = {87}, number = {}, pages = {101154}, doi = {10.1016/j.resmer.2025.101154}, pmid = {39854930}, issn = {2590-0412}, mesh = {Humans ; *Noninvasive Ventilation/methods/statistics & numerical data ; Retrospective Studies ; Male ; Female ; Aged ; Middle Aged ; Cross-Sectional Studies ; *Respiratory Insufficiency/therapy/etiology ; Longitudinal Studies ; Pulmonary Disease, Chronic Obstructive/complications/therapy ; Treatment Outcome ; *Home Care Services ; Obesity Hypoventilation Syndrome/complications ; Amyotrophic Lateral Sclerosis/complications ; *Ambulatory Care ; }, abstract = {INTRODUCTION: Non-invasive ventilation (NIV) is the reference treatment for chronic respiratory failure (CRF) due to impairment of the ventilatory system. Home initiation is increasingly practiced. To better support this ambulatory shift, we aimed to assess the implementation constraints and short-term efficacy according to different aetiologies of CRF.

METHODS: This retrospective study with cross-sectional and longitudinal analysis included patients initiated with NIV at Angers University Hospital. Patients were separated according to the following aetiologies: obesity hypoventilation syndrome (OHS), chronic obstruction pulmonary disease (COPD), amyotrophic lateral sclerosis (ALS), myopathy and chest wall disease. Implementation constraints were assessed by analysing the variability of NIV settings, the number of masks tried and the duration of hospitalisation. NIV effectiveness was assessed by measuring residual PaCO2 (arterial pressure in CO2), apnoea hypopnea index (AHIflow) and tidal volume (VT) (as displayed by the NIV software).

RESULTS: Between October 2020 and May 2022, 102 patients were started with NIV, including a majority of ALS patients. We found a moderate variability in NIV settings (pressure, slope, triggers, etc.) within the different etiological groups, particularly in ALS. On the other hand, ALS patients required more interface trials than other groups and often had unmet efficacy criteria at hospital discharge. Interestingly, longitudinal follow-up showed a progressive improvement in efficacy criteria, particularly in patients who were initially inadequately ventilated.

CONCLUSION: Each aetiological group has specific constraints in the initiation of NIV that should be considered when initiating NIV in the outpatient setting.}, } @article {pmid39854095, year = {2025}, author = {Hansen, G and Shaw, A and Bolt, K and Verity, R and Nataraj, RT and Schellenberg, KL}, title = {Thoracic Electric Impedance Tomography Detects Lung Volume Changes in Amyotrophic Lateral Sclerosis.}, journal = {Muscle & nerve}, volume = {71}, number = {4}, pages = {552-557}, pmid = {39854095}, issn = {1097-4598}, support = {//ALS Society of Saskatchewan/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology/diagnostic imaging ; Male ; Female ; Middle Aged ; *Electric Impedance ; Aged ; Vital Capacity/physiology ; *Tomography/methods ; *Lung/physiopathology/diagnostic imaging ; Spirometry ; Lung Volume Measurements/methods ; Adult ; Supine Position ; }, abstract = {INTRODUCTION/AIMS: Spirometry is the conventional means to measure lung function in amyotrophic lateral sclerosis (ALS), but is dependent on patient effort and bulbar strength. We aimed to use electric impedance tomography (EIT), an emerging non-invasive imaging modality, to measure dynamic lung volume changes.

METHODS: Twenty-one patients with ALS underwent sitting and supine spirometry for forced vital capacity (FVC), and sitting and supine EIT. There were 13 patients in the high FVC group (FVC ≥ 80% predicted) and 8 in the low FVC group (FVC < 80% predicted). Additional demographic and clinical data were collected from clinical records.

RESULTS: Only the low FVC group had significant loss of lung volumes in the supine position (R [2] = 0.89 and p < 0.001). The supine volume loss measurement at 10 min correlated with sitting (r [2] = 0.47) and supine FVC (r [2] = 0.36), maximum inspiratory (r [2] = -0.44) and expiratory pressures (r [2] = 0.36) (MIP and MEP), and the ALS Functional Rating Scale-Revised (ALSFRS-R) dyspnea subscore (r [2] = 0.36).

DISCUSSION: EIT is an emerging alternative to existing measures of lung function in ALS, but without need for patient effort or bulbar strength. Significant losses in lung volume are seen on supine compared to upright position in patients with respiratory dysfunction. Further study is needed to determine relationships to existing clinical measures.}, } @article {pmid39853150, year = {2025}, author = {Shune, S and Gray, LT and Perry, S and Kosty, D and Namasivayam-MacDonald, A}, title = {Validation of the Caregiver Analysis of Reported Experiences with Swallowing Disorders (CARES) Screening Tool for Neurodegenerative Disease.}, journal = {American journal of speech-language pathology}, volume = {34}, number = {2}, pages = {633-645}, doi = {10.1044/2024_AJSLP-24-00253}, pmid = {39853150}, issn = {1558-9110}, mesh = {Humans ; *Deglutition Disorders/diagnosis/etiology/physiopathology/psychology ; Male ; Female ; *Caregivers/psychology ; Aged ; Reproducibility of Results ; Middle Aged ; *Neurodegenerative Diseases/complications/diagnosis ; Amyotrophic Lateral Sclerosis/diagnosis/complications ; Surveys and Questionnaires ; Cost of Illness ; *Deglutition ; *Parkinson Disease/complications/diagnosis ; Aged, 80 and over ; Adult ; Dementia ; ROC Curve ; }, abstract = {PURPOSE: Swallowing difficulties have a substantial impact on the burden experienced by care partners of individuals with neurodegenerative disease. Given this, there is a clear need to easily identify and quantify the unique aspects of swallowing-related burden. The purpose of this study was to establish the validity and reliability of the Caregiver Analysis of Reported Experiences with Swallowing Disorders (CARES) screening tool in care partners of individuals with neurodegenerative disease.

METHOD: Survey data were collected from an international sample of 212 individuals caring for family members with amyotrophic lateral sclerosis (n = 49), dementia (n = 110), or Parkinson's disease (n = 53). Respondents completed the CARES, Eating Assessment Tool-10, International Dysphagia Diet Standardisation Initiative-Functional Diet Scale, and Zarit Burden Interview. Reliability and validity of the CARES were evaluated via internal consistency alpha coefficients, Spearman's rho correlations, and logistic regression analyses with receiver operating characteristic (ROC) curves.

RESULTS: CARES scores demonstrated excellent internal consistency (α = .90-.95) and high test-retest reliability (r = .86-.91). The CARES was found to be valid, as increased swallowing-related burden was associated with increased severity of swallowing difficulties (r = .79 to .84), diet restrictiveness (r = -.50 to -.54), and general caregiver burden (r = .36 to .40). The CARES had excellent discrimination between care partners with and without self-reported swallowing-related burden, with a score of ≥ 4 suggesting a heightened risk of experiencing this burden.

CONCLUSIONS: Results establish the CARES as a valid and reliable screening tool that can detect burden related to swallowing difficulties among care partners of individuals living with neurodegenerative disease (score ≥ 4). Clinical implementation of the CARES requires the concerted efforts of the larger multidisciplinary team who can collaboratively identify the presence of burden and target the multifaceted sources of burden that a care partner may be experiencing.}, } @article {pmid39852553, year = {2025}, author = {Tang, X and Chen, Y and Ren, Y and Yang, W and Yu, W and Zhou, Y and Guo, J and Hu, J and Chen, X and Gu, Y and Wang, C and Dong, Y and Yang, H and Sato, C and He, J and Fan, D and You, L and Zinman, L and Rogaeva, E and Chen, Y and Zhang, M}, title = {Deep learning analyses of splicing variants identify the link of PCP4 with amyotrophic lateral sclerosis.}, journal = {Brain : a journal of neurology}, volume = {148}, number = {7}, pages = {2331-2347}, doi = {10.1093/brain/awaf025}, pmid = {39852553}, issn = {1460-2156}, support = {//National Natural Science Foundation of China/ ; //Shanghai Municipal Natural Science Foundation/ ; //Fundamental Research Funds for the Central Universities/ ; //Brain Science and Brain-Inspired Intelligence Technology/ ; //Ministry of Science and Technology/ ; //G. Harry Sheppard Memorial Research Fund/ ; //Canadian Consortium on Neurodegeneration in Aging/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/genetics ; Humans ; *Deep Learning ; *RNA Splicing/genetics ; *Nerve Tissue Proteins/genetics ; Introns ; Mutation ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a severe motor neuron disease, with most sporadic cases lacking clear genetic causes. Abnormal pre-mRNA splicing is a fundamental mechanism in neurodegenerative diseases. For example, TAR DNA-binding protein 43 (TDP-43) loss of function causes widespread RNA mis-splicing events in ALS. Additionally, splicing mutations are major contributors to neurological disorders. However, the role of intronic variants driving RNA mis-splicing in ALS remains poorly understood. To address this, we developed Spliformer to predict RNA splicing. Spliformer is a transformer-based deep learning model trained and tested on splicing events from the GENCODE database, in addition to RNA-sequencing data from blood and CNS tissues. We benchmarked Spliformer against SpliceAI and Pangolin using testing datasets and paired whole-genome sequencing with RNA-sequencing data. We also developed the Spliformer-motif model to identify splicing regulatory motifs. We analysed the Clinvar dataset to identify the link of splicing variants with disease pathogenicity. Additionally, we analysed whole-genome sequencing data of ALS patients and controls to identify common intronic splicing variants linked to ALS risk or disease phenotypes. We also profiled rare intronic splicing variants in ALS patients to identify known or novel ALS-associated genes. Minigene assays were used to validate candidate splicing variants. Finally, we measured spine density in neurons with a specific gene knockdown or those expressing a TDP-43 disease-causing mutant. Spliformer accurately predicts the possibilities of a nucleotide within a pre-mRNA sequence being a splice donor, acceptor or neither. Spliformer outperformed SpliceAI and Pangolin in both speed and accuracy in tested splicing events and/or paired whole-genome sequencing/RNA-sequencing data. Spliformer-motif successfully identified canonical and novel splicing regulatory motifs. In the Clinvar dataset, splicing variants are highly related to disease pathogenicity. Genome-wide analyses of common intronic splicing variants nominated one variant linked to ALS progression. Deep learning analyses of whole-genome sequencing data from 1370 ALS patients revealed rare splicing variants in reported ALS genes (such as PTPRN2 and CFAP410, validated through minigene assays and RNA sequencing) and TDP-43 loss-of-function-related RNA mis-splicing genes (such as PTPRD). Further genetic analysis and minigene assays nominated PCP4 and TMEM63A as ALS-associated genes. Functional assays demonstrated that PCP4 is crucial for maintaining spine density and can rescue spine loss in neurons expressing a disease-causing TDP-43 mutant. In summary, we developed Spliformer and Spliformer-motif, which accurately predict and interpret pre-mRNA splicing. Our findings highlight an intronic genetic mechanism driving RNA mis-splicing in ALS and nominate PCP4 as an ALS-associated gene.}, } @article {pmid39852477, year = {2025}, author = {Bennett, SA and Cobos, SN and Fisher, RMA and Son, E and Frederic, R and Segal, R and Yousuf, H and Chan, K and Dansu, DK and Torrente, MP}, title = {Direct and Indirect Protein Interactions Link FUS Aggregation to Histone Post-Translational Modification Dysregulation and Growth Suppression in an ALS/FTD Yeast Model.}, journal = {Journal of fungi (Basel, Switzerland)}, volume = {11}, number = {1}, pages = {}, pmid = {39852477}, issn = {2309-608X}, support = {S10 OD010582/OD/NIH HHS/United States ; R35 NS111604/NS/NINDS NIH HHS/United States ; K22NS09131401//NIH NINDS/ ; R35NS111604//NIH NINDS/ ; R15NS125394//NIH NINDS/ ; N/A//Brooklyn College, CUNY/ ; N/A//The Graduate Center, CUNY/ ; K12 GM102778/GM/NIGMS NIH HHS/United States ; R15 NS125394/NS/NINDS NIH HHS/United States ; R15NS125394-01S1//NIH NINDS/ ; K12GM102778//NIH NIGMS/ ; 1S01OD010582-01A1/GF/NIH HHS/United States ; }, abstract = {Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are incurable neurodegenerative disorders sharing pathological and genetic features, including mutations in the FUS gene. FUS is an RNA-binding protein that mislocalizes to the cytoplasm and aggregates in ALS/FTD. In a yeast model, FUS proteinopathy is connected to changes in the epigenome, including reductions in the levels of H3S10ph, H3K14ac, and H3K56ac. Exploiting the same model, we reveal novel connections between FUS aggregation and epigenetic dysregulation. We show that the histone-modifying enzymes Ipl1 and Rtt109-responsible for installing H3S10ph and H3K56ac-are excluded from the nucleus in the context of FUS proteinopathy. Furthermore, we found that Ipl1 colocalizes with FUS, but does not bind it directly. We identified Nop1 and Rrp5, a histone methyltransferase and rRNA biogenesis protein, respectively, as FUS binding partners involved in the growth suppression phenotype connected to FUS proteinopathy. We propose that the nuclear exclusion of Ipl1 through indirect interaction with FUS drives the dysregulation of H3S10ph as well as H3K14ac via crosstalk. We found that the knockdown of Nop1 interferes with these processes. In a parallel mechanism, Rtt109 mislocalization results in reduced levels of H3K56ac. Our results highlight the contribution of epigenetic mechanisms to ALS/FTD and identify novel targets for possible therapeutic intervention.}, } @article {pmid39851451, year = {2025}, author = {Milligan, C and Cowley, DO and Stewart, W and Curry, AM and Forbes, E and Rector, B and Hastie, A and Liu, L and Hawkins, GA}, title = {Enhanced Interleukin 6 Trans-Signaling Modulates Disease Process in Amyotrophic Lateral Sclerosis Mouse Models.}, journal = {Brain sciences}, volume = {15}, number = {1}, pages = {}, pmid = {39851451}, issn = {2076-3425}, support = {R03 AI137866/AI/NIAID NIH HHS/United States ; Hope for Tomorrow ALS Fund//Wake Forest University School of Medicine/ ; 1R03AI137866-21A1/NH/NIH HHS/United States ; DoD W81XWH1810377//US Department of the Army/ ; Neuroscience Clinical Trial and Innovation Center//Wake Forest University School of Medicine/ ; UL1 TR001420/TR/NCATS NIH HHS/United States ; TAB Williams Endowment//Wake Forest University School of Medicine/ ; }, abstract = {Background/Objectives: Charcot first described ALS in 1869, but the specific mechanisms that mediate the disease pathology are still not clear. Intense research efforts have provided insight into unique neuroanatomical regions, specific neuronal populations and genetic associations for ALS and other neurodegenerative diseases; however, the experimental results also suggest a convergence of these events to common toxic pathways. We propose that common toxic pathways can be therapeutically targeted, and this intervention will be effective in slowing progression and improving patient quality of life. Here, we focus on understanding the role of IL6 trans-signaling in ALS disease processes. Methods: We leveraged unique mouse models of IL6 trans-signaling that we developed that recapitulate the production of active sIL6R in a genotypic and quantitative fashion observed in humans. Given that the SOD1 transgenic mouse is one of the most highly studied and characterized models of ALS, we bred SOD1[G93A] mice with IL6R trans-signaling mice to determine how enhanced trans-signaling influenced symptom onset and pathological processes, including neuromuscular junction (NMJ) denervation, glial activation and motoneuron (MN) survival. Results: The results indicate that in animals with enhanced trans-signaling, symptom onset and pathological processes were accelerated, suggesting a role in disease modification. Administration of an IL6R functional blocking antibody failed to alter accelerated symptom onset and disease progression. Conclusions: Future work to investigate the site-specific influence of enhanced IL6 trans-signaling and the tissue-specific bioavailability of potential therapeutics will be necessary to identify targets for precise therapeutic interventions that may limit disease progression in the 60% of ALS patients who inherit the common Il6R Asp[358]Ala variant.}, } @article {pmid39850989, year = {2025}, author = {Matsuda, C and Nakayama, Y and Haraguchi, M and Morishima, R and Itagaki, Y and Bokuda, K and Kimura, H and Takahashi, K and Shimizu, T}, title = {Patients' choices regarding ventilatory support affect opioid use in amyotrophic lateral sclerosis.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {26}, number = {5-6}, pages = {409-416}, doi = {10.1080/21678421.2025.2453463}, pmid = {39850989}, issn = {2167-9223}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy/psychology ; Male ; Female ; *Analgesics, Opioid/therapeutic use ; Middle Aged ; Retrospective Studies ; Aged ; *Respiration, Artificial/methods ; Noninvasive Ventilation ; Adult ; Respiratory Insufficiency/therapy/etiology ; *Choice Behavior ; }, abstract = {OBJECTIVE: To investigate the impact of different ventilatory support options on opioid use among patients with amyotrophic lateral sclerosis (ALS).

METHODS: We retrospectively reviewed 889 consecutive patients with ALS and enrolled 399 eligible patients. All patients were followed until death or tracheostomy. Clinical characteristics of patients and the timing of initial opioid administration were evaluated. Patients were categorized into four subgroups: (1) 160 patients who never used a ventilator, (2) 120 patients who used only noninvasive ventilation (NIV), (3) 61 patients who transitioned from NIV to tracheostomy and invasive ventilation (TIV), and (4) 58 patients who underwent TIV without prior NIV. We compared the prevalence of opioid use across these groups and assessed its relationship with ventilatory support options using multivariate logistic analysis.

RESULTS: A total of 130 patients (32.6%) used opioids. The number of patients who used opioids in each group was as follows: 55 (34.4%) in Group 1, 69 (57.5%) in Group 2, 5 (8.2%) in Group 3, and 1 (1.7%) in Group 4 (p < 0.0001). Multivariate logistic analysis revealed that, compared to Group 1, the use of NIV only was positively associated with opioid use (p = 0.002). In contrast, transitioning from NIV to TIV (Group 3) and using TIV only (Group 4) were negatively associated with opioid use (p = 0.0001 and 0.001, respectively).

CONCLUSIONS: The choice of ventilatory support significantly influences opioid use in patients with ALS. Patients who opted against TIV required opioids to relieve distress more commonly than those who chose TIV.}, } @article {pmid39849490, year = {2025}, author = {Álvarez-Sánchez, E and Carbayo, Á and Valle-Tamayo, N and Muñoz, L and Aumatell, J and Torres, S and Rubio-Guerra, S and García-Castro, J and Selma-González, J and Alcolea, D and Turon-Sans, J and Lleó, A and Illán-Gala, I and Fortea, J and Rojas-García, R and Dols-Icardo, O}, title = {Single-cell RNA sequencing highlights the role of distinct natural killer subsets in sporadic amyotrophic lateral sclerosis.}, journal = {Journal of neuroinflammation}, volume = {22}, number = {1}, pages = {15}, pmid = {39849490}, issn = {1742-2094}, support = {PI21/00791//Instituto de Salud Carlos III (Ministerio de Asuntos Económicos y Transformación Digital, Gobierno de España)/ ; AARF-22-924456/ALZ/Alzheimer's Association/United States ; R01 AG056850/NH/NIH HHS/United States ; Por un mundo sin ELA//Fundación Española para el Fomento de la Investigación de la Esclerosis Lateral Amiotrófica/ ; INT21/00073//Instituto de Salud Carlos III (Ministerio de Asuntos Económicos y Transformación Digital, Gobierno de España)/ ; PI19/01543//Instituto de Salud Carlos III (Ministerio de Asuntos Económicos y Transformación Digital, Gobierno de España)/ ; PDC-2023-51; #202307//Fondation Jérôme Lejeune/ ; RF1 AG056850/AG/NIA NIH HHS/United States ; AACSF-21-850193/ALZ/Alzheimer's Association/United States ; FI22/00077//Instituto de Salud Carlos III (Ministerio de Asuntos Económicos y Transformación Digital, Gobierno de España)/ ; GBHI ALZ UK-21-720973//Global Brain Health Institute/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/immunology/genetics/blood/pathology ; Male ; Female ; *Killer Cells, Natural/metabolism/immunology ; Middle Aged ; *Sequence Analysis, RNA/methods ; Aged ; *Single-Cell Analysis/methods ; Leukocytes, Mononuclear/metabolism ; Adult ; }, abstract = {BACKGROUND: Neuroinflammation plays a major role in amyotrophic lateral sclerosis (ALS), and cumulative evidence suggests that systemic inflammation and the infiltration of immune cells into the brain contribute to this process. However, no study has investigated the role of peripheral blood immune cells in ALS pathophysiology using single-cell RNA sequencing (scRNAseq).

METHODS: We aimed to characterize immune cells from blood and identify ALS-related immune alterations at single-cell resolution. For this purpose, peripheral blood mononuclear cells (PBMC) were isolated from 14 ALS patients and 14 cognitively unimpaired healthy individuals (HC), matched by age and gender, and cryopreserved until library preparation and scRNAseq. We analyzed differences in the proportions of PBMC, gene expression, and cell-cell communication patterns between ALS patients and HC, as well as their association with plasma neurofilament light (NfL) concentrations, a surrogate biomarker for neurodegeneration. Flow cytometry was used to validate alterations in cell type proportions.

RESULTS: We identified the expansion of CD56[dim] natural killer (NK) cells in ALS (fold change = 2; adj. p-value = 0.0051), mainly driven by a specific subpopulation, NK_2 cells (fold change = 3.12; adj. p-value = 0.0001), which represent a mature and cytotoxic CD56[dim] NK subset. Our results revealed extensive gene expression alterations in NK_2 cells, pointing towards the activation of immune response (adj. p-value = 9.2 × 10[- 11]) and the regulation of lymphocyte proliferation (adj. p-value = 6.46 × 10[- 6]). We also identified gene expression changes in other immune cells, such as classical monocytes, and distinct CD8 + effector memory T cells which suggested enhanced antigen presentation via major histocompatibility class-II (adj. p-value = 1.23 × 10[- 8]) in ALS. The inference of cell-cell communication patterns demonstrated that the interaction between HLA-E and CD94:NKG2C from different lymphocytes to NK_2 cells is unique to ALS blood compared to HC. Finally, regression analysis revealed that the proportion of CD56[bright] NK cells along with the ALSFRS-r, disease duration, and gender, explained up to 76.4% of the variance in plasma NfL levels.

CONCLUSION: Our results reveal a signature of relevant changes occurring in peripheral blood immune cells in ALS and underscore alterations in the proportion, gene expression, and signaling patterns of a cytotoxic and terminally differentiated CD56[dim] NK subpopulation (NK_2), as well as a possible role of CD56[bright] NK cells in neurodegeneration.}, } @article {pmid39849126, year = {2025}, author = {Gupta, S and Kishore, A and Rishi, V and Aggarwal, A}, title = {Mitochondria and its epigenetic dynamics: Insight into synaptic regulation and synaptopathies.}, journal = {Functional & integrative genomics}, volume = {25}, number = {1}, pages = {26}, pmid = {39849126}, issn = {1438-7948}, mesh = {Humans ; *Mitochondria/metabolism/genetics ; *Epigenesis, Genetic ; *Synapses/metabolism/genetics/pathology ; *Mitochondrial Dynamics/genetics ; Animals ; Synaptic Transmission ; Calcium/metabolism ; }, abstract = {Mitochondria, the cellular powerhouses, are pivotal to neuronal function and health, particularly through their role in regulating synaptic structure and function. Spine reprogramming, which underlies synapse development, depends heavily on mitochondrial dynamics-such as biogenesis, fission, fusion, and mitophagy as well as functions including ATP production, calcium (Ca[2+]) regulation, and retrograde signaling. Mitochondria supply the energy necessary for assisting synapse development and plasticity, while also regulating intracellular Ca[2+] homeostasis to prevent excitotoxicity and support synaptic neurotransmission. Additionally, the dynamic processes of mitochondria ensure mitochondrial quality and adaptability, which are essential for maintaining effective synaptic activity. Emerging evidence highlights the significant role of epigenetic modifications in regulating mitochondrial dynamics and function. Epigenetic changes influence gene expression, which in turn affects mitochondrial activity, ensuring coordinated responses necessary for synapse development. Furthermore, metabolic changes within mitochondria can impact the epigenetic machinery, thereby modulating gene expression patterns that support synaptic integrity. Altered epigenetic regulation affecting mitochondrial dynamics and functions is linked to several neurological disorders, including Amyotrophic Lateral Sclerosis, Huntington's, Alzheimer's, and Parkinson's diseases, emphasizing its crucial function. The review delves into the molecular machinery involved in mitochondrial dynamics, ATP and Ca[2+] regulation, highlighting the role of key proteins that facilitate the processes. Additionally, it also shed light on the emerging epigenetic factors influencing these regulations. It provides a thorough summary on the current understanding of the role of mitochondria in synapse development and emphasizes the importance of both molecular and epigenetic mechanisms in maintaining synaptic integrity.}, } @article {pmid39845951, year = {2024}, author = {Zucchi, E and Banchelli, F and Simonini, C and De Biasi, S and Martinelli, I and Gianferrari, G and Lo Tartaro, D and Cossarizza, A and D'Amico, R and Mandrioli, J}, title = {Tregs levels and phenotype modifications during Amyotrophic Lateral Sclerosis course.}, journal = {Frontiers in immunology}, volume = {15}, number = {}, pages = {1508974}, pmid = {39845951}, issn = {1664-3224}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/immunology/diagnosis ; Male ; Female ; Middle Aged ; *T-Lymphocytes, Regulatory/immunology/metabolism ; Disease Progression ; Aged ; Phenotype ; Biomarkers ; Immunophenotyping ; Adult ; }, abstract = {INTRODUCTION: T regulatory cells (Tregs) inversely correlate with disease progression in Amyotrophic Lateral Sclerosis (ALS) and fast-progressing ALS patients have been reported to exhibit dysfunctional, as well as reduced, levels of Tregs. This study aimed to evaluate the longitudinal changes in Tregs among ALS patients, considering potential clinical and biological modifiers of their percentages and concentrations. Additionally, we explored whether measures of ALS progression, such as the decline over time in the revised ALS Functional Rating Scale (ALSFRS-r) or forced vital capacity (FVC) correlated Treg levels and whether Treg phenotype varied during the course of ALS.

METHODS: Total Tregs (detected by CD3, CD4, FoxP3, CD25, and CD127) were quantified at five time points over 54 weeks in 21 patients in the placebo arm of the RAP-ALS trial; next they were characterized for the expression of surface markers including CD38, CD39, CXCR3, and PD1. Repeated measures mixed models were used to analyze the longitudinal course of Tregs, considering potential associations with other clinical and laboratory characteristics. Correlations between ALSFRS-r or FVC and Tregs over time were similarly investigated.

RESULTS: Our study showed that Treg levels did not change significantly on average during the observation period in our ALS cohort. However, PD1+Tregs decreased and CD39+Tregs increased over time. Male sex and cholesterol levels were associated with increasing Tregs (%) over time, while monocytes positively affected Treg concentrations. Treg concentrations showed a modesty association with FVC decline but were not associated with ALSFRS-r decline.

DISCUSSION: Treg levels remained stable during the ALS observation period and were not significantly associated with ALSFRS-r variations, suggesting that Treg numbers alone may have limited utility as a pharmaco-dynamic biomarker for ALS trials. However the observed changes in Treg phenotypes, such as the decrease in PD1+Tregs, indicate that phenotypic variations may warrant further investigation for their potential role in ALS progression and therapeutic targeting.}, } @article {pmid39845577, year = {2025}, author = {Ludolph, A and Wiesenfarth, M}, title = {Tofersen and other antisense oligonucleotides in ALS.}, journal = {Therapeutic advances in neurological disorders}, volume = {18}, number = {}, pages = {17562864251313915}, pmid = {39845577}, issn = {1756-2856}, abstract = {The advent of antisense oligonucleotide (ASO) therapies in neurodegenerative disorders is associated with enormous hope. Nusinersen treatment was a breakthrough intervention in the recessive disease spinal muscular atrophy, and superoxide dismutase 1 (SOD1) amyotrophic lateral sclerosis (ALS) seems to be the paradigm disease in dominant degenerative diseases. The results of treatment with the ASO tofersen in SOD1-ALS show that the drug has a convincing beneficial effect on ALS caused by SOD1 mutations, that preclinical studies in rodents predicted the therapeutic effect in the human disease, and that clinical efficacy is associated with a specific sequence of effects of the drug on mechanistic and degenerative biomarkers and, subsequently, functional outcomes such as weight stabilization and ALSFRS-R. Therefore, the enthusiasm seems to be justified; but this should be followed by an attempt to obtain further insights with the goal to improve this therapy. In particular, the following issues are only partially resolved: Which mechanisms are responsible for the clinical effect following the downregulation of SOD1 protein by ASOs? Is long-term downregulation of SOD1 function associated with side effects? Is there an autoimmune response caused by this and other ASO? Is prevention of SOD1-associated ALS possible?}, } @article {pmid39844967, year = {2025}, author = {de Melo, R and Alcantara, L and Sarmet, M and Sheers, NL and Berlowitz, DJ and Maldaner, V}, title = {Use of Lung Volume Recruitment Technique in Patients With Chronic Respiratory Disease Among Brazilian Health Professionals.}, journal = {Pulmonary medicine}, volume = {2025}, number = {}, pages = {4073171}, pmid = {39844967}, issn = {2090-1844}, mesh = {Humans ; Brazil ; Cross-Sectional Studies ; Male ; Female ; Adult ; *Respiratory Therapy/methods ; *Health Personnel/statistics & numerical data ; Chronic Disease ; *Allied Health Personnel/statistics & numerical data ; Surveys and Questionnaires ; }, abstract = {Background: Lung volume recruitment (LVR) is a stacked-breath assisted inflation technique in which consecutive insufflations are delivered, without exhaling in between, until the maximum tolerable inflation capacity is reached. Although LVR is recommended in some neuromuscular disease guidelines, there is little information detailing when and how allied health professionals (AHPs) prescribe LVR. Objective: This study is aimed at describing the use of LVR in practice across Brazil. Methods: A cross-sectional e-survey (Sep-Nov 2023) explored LVR practices among qualified clinical or home care AHPs in Brazil. It gathered participant data on geographical region, profession, and experience. It delved into LVR specifics: clinical population and indications for use, prescription (frequency, dosage, and interfaces), related side effects, outcomes assessed, and combined therapies. Results were presented descriptively. Results: One hundred two surveys (74 physical therapists (PTs) and 28 speech and language pathologists (SLPs)) from diverse locations were collected. LVR was predominantly prescribed for adults (57%), with the most common diagnosis being amyotrophic lateral sclerosis (84%). Changes in peak cough flow and vital capacity were the most common reasons for LVR prescription. Maximal insufflation capacity was reportedly measured by 58% of PTs and 22% of SLPs. Chest wall soreness and discomfort were the most common side effects, and many respondents did not provide warnings about potential side effects (42% PTs and 50% SLPs). The study highlighted common use of other respiratory therapy devices alongside LVR. Conclusion: LVR is available in routine clinical and home care settings in Brazil. There is a lack of standardization regarding indications, prescription, and outcome measures among PTs and SLPs in Brazil. Clear recommendations and guidelines are needed to standardize these parameters, enabling more objective data and facilitating comparisons between centers.}, } @article {pmid39844875, year = {2024}, author = {Kõks, S and Rallmann, K and Muldmaa, M and Price, J and Pfaff, AL and Taba, P}, title = {Whole blood transcriptome profile identifies motor neurone disease RNA biomarker signatures.}, journal = {Experimental biology and medicine (Maywood, N.J.)}, volume = {249}, number = {}, pages = {10401}, pmid = {39844875}, issn = {1535-3699}, mesh = {Humans ; *Biomarkers/blood ; Male ; Female ; *Transcriptome/genetics ; Middle Aged ; *Motor Neuron Disease/genetics/blood ; *Gene Expression Profiling ; Aged ; *RNA/blood/genetics ; Case-Control Studies ; Adult ; }, abstract = {Blood-based biomarkers for motor neuron disease are needed for better diagnosis, progression prediction, and clinical trial monitoring. We used whole blood-derived total RNA and performed whole transcriptome analysis to compare the gene expression profiles in (motor neurone disease) MND patients to the control subjects. We compared 42 MND patients to 42 aged and sex-matched healthy controls and described the whole transcriptome profile characteristic for MND. In addition to the formal differential analysis, we performed functional annotation of the genomics data and identified the molecular pathways that are differentially regulated in MND patients. We identified 12,972 genes differentially expressed in the blood of MND patients compared to age and sex-matched controls. Functional genomic annotation identified activation of the pathways related to neurodegeneration, RNA transcription, RNA splicing and extracellular matrix reorganisation. Blood-based whole transcriptomic analysis can reliably differentiate MND patients from controls and can provide useful information for the clinical management of the disease and clinical trials.}, } @article {pmid39844762, year = {2025}, author = {Theuriet, J and Bernard, E and Guy, N and Taithe, F and Even, C and Maisonobe, T and Sangaré, A and Lardeux, P and Tilikete, CF and Couratier, P and Lenglet, T and Pegat, A}, title = {Electrophysiological Abnormalities in Finger Extension Weakness and DOwnbeat Nystagmus Motor Neuron Disease: Three New Patients and Review of the Literature.}, journal = {Muscle & nerve}, volume = {71}, number = {4}, pages = {644-650}, pmid = {39844762}, issn = {1097-4598}, mesh = {Humans ; *Motor Neuron Disease/physiopathology/complications/diagnosis ; Male ; Electromyography ; *Nystagmus, Pathologic/physiopathology/complications/diagnosis ; Female ; Middle Aged ; *Fingers/physiopathology ; *Muscle Weakness/physiopathology/etiology/diagnosis ; Adult ; Neural Conduction/physiology ; Action Potentials/physiology ; Muscle, Skeletal/physiopathology ; }, abstract = {INTRODUCTION/AIMS: Finger Extension Weakness and DOwnbeat Nystagmus Motor Neuron Disease (FEWDON-MND) is characterized by motor weakness predominantly affecting finger extension, accompanied by downbeat nystagmus. To date, only 11 patients have been reported. The present study adds a further three and aims to provide a more detailed description of the electrodiagnostic features of these patients.

METHODS: We present the clinical and electrophysiological features of three French patients from specialized motor neuron centers and review the electrophysiological findings of previously reported patients.

RESULTS: These three patients presented with pure motor weakness affecting finger extension and downbeat nystagmus. They exhibited a slowly progressive disease course without respiratory involvement. Nerve conduction studies showed decreased compound muscle action potential amplitudes in the extensor indicis muscles. Abnormal spontaneous activity on needle electromyography (EMG) was rare in two patients, absent in one, and otherwise limited to weak muscles. Additionally, chronic motor axon loss features suggestive of motor neuronopathy were seen in our patients. Importantly, they were also detected in distant asymptomatic muscles.

DISCUSSION: The three patients reported here confirm the typical phenotype of FEWDON-MND, characterized by slowly progressive distal motor weakness initially affecting finger extension, associated with downbeat nystagmus. Although chronic motor axon loss features have been found in all reported patients, our three patients show that active denervation can be absent or rare. Thus, finger drop and diffuse chronic neurogenic changes on EMG should lead clinicians to look for downbeat nystagmus and to consider FEWDON-MND.}, } @article {pmid39843865, year = {2025}, author = {Calancie, B and Alexeeva, N}, title = {Revisiting motor unit recruitment to TMS in amyotrophic lateral sclerosis: cortical inhibition is retained during voluntary contractions.}, journal = {Experimental brain research}, volume = {243}, number = {2}, pages = {51}, pmid = {39843865}, issn = {1432-1106}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology/pathology ; *Transcranial Magnetic Stimulation/methods ; Male ; Female ; Middle Aged ; *Recruitment, Neurophysiological/physiology ; Electromyography ; *Muscle Contraction/physiology ; Aged ; Muscle, Skeletal/physiopathology ; *Neural Inhibition/physiology ; *Motor Cortex/physiopathology ; Evoked Potentials, Motor/physiology ; Adult ; *Motor Neurons/physiology ; }, abstract = {Transcranial magnetic stimulation (TMS) has been used for many years to study the pathophysiology of amyotrophic lateral sclerosis (ALS). Based on single- or dual-pulse TMS and EMG and/or single motor unit (MU) recordings, many groups have described a loss of central inhibition as an early marker of ALS dysfunction, reflecting a state of cortical 'hyperexcitability'. This conclusion is not without its detractors, however, leading us to reexamine this issue using 4-pulse TMS, shown previously to be more effective for testing central motor pathway functional integrity. A total of 221 motor units were tested in 13 subjects (6 controls; 7 with ALS) across a total of 798 unique TMS conditions. MUs were studied from hand muscles (usually first dorsal interosseus) and from tibialis anterior (TA). Subjects were required to recruit a MU to fire rhythmically, during which time 4-pulse trains of TMS were delivered. A given motor unit's recruitment was examined for different stimulus intensities and interpulse intervals (IPI). All motor units from control subjects showed short latency excitation to TMS, and short latency inhibition for TMS pulses of slightly weaker intensity (i.e. the threshold for inhibition was lower than that for excitation). The same was largely true for MUs studied in subjects with ALS, with the primary difference between control and ALS subjects being the need for stronger stimulus intensities to effect recruitment in subjects with ALS. We saw no evidence for a loss or reduction of inhibition of central motor output in persons with ALS, at least when tested during voluntary contractions.}, } @article {pmid39842380, year = {2025}, author = {Faltracco, V and Pain, D and Dalla Bella, E and Riva, N and Telesca, A and Soldini, E and Gandini, G and Radici, A and Poletti, B and Lauria, G and Consonni, M}, title = {Mood disorders in patients with motor neuron disease and frontotemporal symptoms: Validation of the Hospital Anxiety and Depression Scale for use in motor neuron disease.}, journal = {Journal of the neurological sciences}, volume = {469}, number = {}, pages = {123378}, doi = {10.1016/j.jns.2024.123378}, pmid = {39842380}, issn = {1878-5883}, mesh = {Humans ; Female ; Male ; *Motor Neuron Disease/psychology/complications ; Middle Aged ; *Mood Disorders/diagnosis/etiology/psychology/complications ; Aged ; *Psychiatric Status Rating Scales/standards ; *Anxiety/diagnosis/etiology ; Reproducibility of Results ; *Depression/diagnosis/etiology ; Adult ; Neuropsychological Tests ; }, abstract = {BACKGROUND: Motor neuron disease (MND) is a heterogeneous neurodegenerative disorder, with nearly 50 % of patients exhibiting cognitive and behavioral symptoms in addition to motor decline. Anxiety and depression, though frequently observed in this population, have been understudied in relation to motor and extra-motor profiles.

OBJECTIVES: Our study addresses this gap by validating the Hospital Anxiety and Depression Scale for Motor Neuron Disease (HADS-MND) and investigating the interplay between mood, clincial, and frontotemporal symptoms in a large sample of MND patients.

METHODS: A total of 249 MND patients underwent clinical, genetic, and neuropsychological assessments. The validity, reliability, sensitivity, and specificity of the HADS-MND global score and subscores were explored. Correlation analyses and group comparisons tested the link between mood, motor and extra-motor profiles.

RESULTS: The bidirectional structure of the HADS-MND was confirmed, but receiver operating characteristics analysis suggests caution for clinical use of the anxiety and depression subscales. The global HADS-MND score is recommended as a measure of psychological distress, with a cut-off point of 10 detecting 38 % of patients with altered scores. Moderate symptoms of anxiety and depression were present in 14 % and 11 % of cases, respectively. Depressive mood was higher in women, patients with frontotemporal symptoms, and severe motor-functional disabilities. Depressive and/or anxiety symptoms were linked to loneliness, behavioral changes, emotional dysregulation, and poor quality of life. Cognitive efficiency was not associated with mood.

CONCLUSION: Mood disorders appeared independent of cognitive profiles but related to behavioral changes. This is particularly relevant for clinicians discussing end-of-life decisions with patients.}, } @article {pmid39841674, year = {2025}, author = {Grapperon, AM and El Mendili, MM and Maarouf, A and Ranjeva, JP and Guye, M and Verschueren, A and Attarian, S and Zaaraoui, W}, title = {In vivo mapping of sodium homeostasis disturbances in individual ALS patients: A brain 23Na MRI study.}, journal = {PloS one}, volume = {20}, number = {1}, pages = {e0316916}, pmid = {39841674}, issn = {1932-6203}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism/diagnostic imaging/pathology ; Male ; Female ; *Magnetic Resonance Imaging/methods ; Middle Aged ; *Homeostasis ; *Sodium/metabolism ; *Brain/metabolism/diagnostic imaging ; Aged ; Adult ; Sodium Isotopes ; Brain Mapping ; }, abstract = {OBJECTIVE: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by significant heterogeneity among patients. 23Na MRI maps abnormal sodium homeostasis that reflects metabolic alterations and energetic failure contributing to the neurodegenerative process. In this study, we investigated disease severity at the individual level in ALS patients using brain 23Na MRI.

METHODS: 1H and 23Na brain MRI were collected prospectively from 28 ALS patients. Individual map of abnormal total sodium concentration (TSC) was computed using voxel-based statistical mapping for each patient compared to a local database of 62 healthy controls. Clinical data included the revised ALS functional rating scale (ALSFRS-R), ALSFRS-R slope, ALSFRS-R at 6-month and survival time.

RESULTS: Individual maps quantifying voxels with TSC increase evidenced a high heterogeneity between patients consistent with clinical presentation. The main areas involved were the corticospinal tracts. Half of patients showed abnormal TSC increase within more than 1% of whole brain voxels. Patients with TSC increase had worse clinical severity: higher ALSFRS-R slope (p = 0.02), lower ALSFRS-R at 6-month (p = 0.04), and shorter survival (p = 0.04). ALS patients with limited TSC increase had slower progression of disability or predominant lower motor neuron phenotype or shorter disease duration.

DISCUSSION: This study mapping sodium homeostasis disturbances at the individual level in ALS patients through 23Na MRI evidenced heterogeneity of TSC increase among patients associated with clinical presentation and disease severity. These findings suggest that TSC increase detected at the individual level by 23Na MRI may be a useful marker of the clinical heterogeneity of ALS patients, a factor that is likely to greatly influence the results of therapeutic trials.}, } @article {pmid39841625, year = {2025}, author = {Hoengenaert, L and Anders, C and Van Doorsselaere, J and Vanholme, R and Boerjan, W}, title = {Transgene-free genome editing in poplar.}, journal = {The New phytologist}, volume = {247}, number = {1}, pages = {224-232}, doi = {10.1111/nph.20415}, pmid = {39841625}, issn = {1469-8137}, support = {//Universiteit Gent/ ; G011620N//Fonds Wetenschappelijk Onderzoek/ ; //Energy Transition Fund/ ; //Advanced ERC grant POPMET/ ; }, mesh = {*Populus/genetics ; *Gene Editing/methods ; *Transgenes/genetics ; *Genome, Plant/genetics ; Plants, Genetically Modified ; DNA, Bacterial/genetics ; }, abstract = {Precise gene-editing methods are valuable tools to enhance genetic traits. Gene editing is commonly achieved via stable integration of a gene-editing cassette in the plant's genome. However, this technique is unfavorable for field applications, especially in vegetatively propagated plants, such as many commercial tree species, where the gene-editing cassette cannot be segregated away without breaking the genetic constitution of the elite variety. Here, we describe an efficient method for generating gene-edited Populus tremula × P. alba (poplar) trees without incorporating foreign DNA into its genome. Using Agrobacterium tumefaciens, we expressed a base-editing construct targeting CCoAOMT1 along with the ALS genes for positive selection on a chlorsulfuron-containing medium. About 50% of the regenerated shoots were derived from transient transformation and were free of T-DNA. Overall, 7% of the chlorsulfuron-resistant shoots were T-DNA free, edited in the CCoAOMT1 gene and nonchimeric. Long-read whole-genome sequencing confirmed the absence of any foreign DNA in the tested gene-edited lines. Additionally, we evaluated the CodA gene as a negative selection marker to eliminate lines that stably incorporated the T-DNA into their genome. Although the latter negative selection is not essential for selecting transgene-free, gene-edited Populus tremula × P. alba shoots, it may prove valuable for other genotypes or varieties.}, } @article {pmid39840922, year = {2025}, author = {Saucier, D and Bélanger, M and Liu, Z and Lavigne, E and O'Connell, C}, title = {Associations between water exposure and the development of amyotrophic lateral sclerosis: a matched case-control study.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {26}, number = {3-4}, pages = {281-289}, doi = {10.1080/21678421.2025.2453450}, pmid = {39840922}, issn = {2167-9223}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/epidemiology/etiology/diagnosis ; Female ; Male ; Case-Control Studies ; Middle Aged ; Aged ; *Environmental Exposure/adverse effects ; }, abstract = {OBJECTIVE: Previous studies have hinted at an association between water exposure and the development of ALS. However, proximity measures to these water sources have been limited to questionnaires or large buffers due to a lack of fine geospatial measures. They also do not distinguish the various classes of hydrographic features. Thus, we created a robust database to investigate the association between proximity to water bodies at place of residence and the development of ALS.

METHODS: A matched (sex and year of birth) case-control study was conducted in New Brunswick, Canada from January 2003 to February 2021. Study population included 304 ALS patients and 1207 controls with their historical postal codes linked to spatial proximity datasets and air pollution index indicators (proxy measures for contamination by run-off).

RESULTS: Odds of ALS were not significantly associated with proximity to water bodies, even within a 250 m buffer from place of residence (Oceans: 1.10, 0.60-2.00 [95% CI], Reservoirs/Ponds/Lakes: 1.24, 0.47-3.30 [95% CI]). As for interaction models investigating proximity to potentially contaminated water bodies, none of the final fitted models observed an association between proximity to water bodies with indicators of potential run-off sources and the development of ALS.

CONCLUSIONS: No significant association between proximity to water bodies at place of residence and the development of ALS were observed in the current study. Future studies should consider taking direct measurements of water quality or utilize geomaps of spraying activities and cyanobacteria blooms alongside proximity measures. Household water quality is another avenue to explore, particularly well water use.}, } @article {pmid39840885, year = {2025}, author = {McKinnon, S and Qiang, Z and Keerie, A and Wells, T and Shaw, PJ and Alix, JJP and Mead, RJ}, title = {Maximizing the translational potential of neurophysiology in amyotrophic lateral sclerosis: a study on compound muscle action potentials.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {26}, number = {3-4}, pages = {322-330}, doi = {10.1080/21678421.2024.2448540}, pmid = {39840885}, issn = {2167-9223}, mesh = {*Amyotrophic Lateral Sclerosis/physiopathology/genetics ; Animals ; Humans ; *Action Potentials/physiology ; *Muscle, Skeletal/physiopathology ; Mice ; Disease Models, Animal ; Mice, Transgenic ; Male ; Female ; *Translational Research, Biomedical ; Middle Aged ; Motor Neurons/physiology ; Superoxide Dismutase-1/genetics ; Superoxide Dismutase/genetics ; Aged ; *Neurophysiology ; }, abstract = {Mouse models of amyotrophic lateral sclerosis (ALS) enable testing of novel therapeutic interventions. However, treatments that have extended survival in mice have often failed to translate into human benefit in clinical trials. Compound muscle action potentials (CMAPs) are a simple neurophysiological test that measures the summation of muscle fiber depolarization in response to maximal stimulation of the innervating nerve. CMAPs can be measured in both mice and humans and decline with motor axon loss in ALS, making them a potential translational read-out of disease progression. We assessed the translational potential of CMAPs and ascertained time points when human and mouse data aligned most closely. We extracted data from 18 human studies and compared with results generated from SOD1[G93A] and control mice at different ages across different muscles. The relative CMAP amplitude difference between SOD1[G93A] and control mice in tibialis anterior (TA) and gastrocnemius muscles at 70 days of age was most similar to the relative difference between baseline ALS patient CMAP measurements and healthy controls in the abductor pollicis brevis (APB) muscle. We also found that the relative decline in SOD1[G93A] TA CMAP amplitude between 70 and 140 days was similar to that observed in 12 month human longitudinal studies in APB. Our findings suggest CMAP amplitudes can provide a "translational window", from which to make comparisons between the SOD1[G93A] model and human ALS patients. CMAPs are easy to perform and can help determine the most clinically relevant starting/end points for preclinical studies and provide a basis for predicting potential clinical effect sizes.}, } @article {pmid39840019, year = {2024}, author = {De Cleene, N and Schwarzová, K and Labrecque, S and Cerejo, C and Djamshidian, A and Seppi, K and Heim, B}, title = {Olfactory dysfunction as potential biomarker in neurodegenerative diseases: a narrative review.}, journal = {Frontiers in neuroscience}, volume = {18}, number = {}, pages = {1505029}, pmid = {39840019}, issn = {1662-4548}, abstract = {Neurodegenerative diseases represent a group of disorders characterized by progressive degeneration of neurons in the central nervous system, leading to a range of cognitive, motor, and sensory impairments. In recent years, there has been growing interest in the association between neurodegenerative diseases and olfactory dysfunction (OD). Characterized by a decline in the ability to detect or identify odors, OD has been observed in various conditions, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and Amyotrophic Lateral Sclerosis (ALS). This phenomenon often precedes the onset of other clinical symptoms, suggesting its potential utility as an early marker or prodromal symptom of neurodegenerative diseases. This review provides a vast literature overview on the current knowledge of OD in PD, AD, ALS, and HD in order to evaluate its potential as a biomarker, particularly in the early and prodromal stages of these diseases. We summarize the most common methods used to measure olfactory function and delve into neuropathological correlations and the alterations in neurotransmitter systems associated with OD in those neurodegenerative diseases, including differences in genetic variants if applicable, and cater to current pitfalls and shortcomings in the research.}, } @article {pmid39840015, year = {2024}, author = {Yang, J and Li, W and Tian, M and Zhang, L and Du, F and Li, X and Liu, Q and Li, R and Li, Z and Dong, H and Liu, Y}, title = {Cortical thickness correlated with peripheral inflammatory cytokines in amyotrophic lateral sclerosis.}, journal = {Frontiers in neuroscience}, volume = {18}, number = {}, pages = {1514554}, pmid = {39840015}, issn = {1662-4548}, abstract = {INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a rare, devastating neurodegenerative disease that affects upper and lower motor neurons, resulting in muscle atrophy, spasticity, hyperreflexia, and paralysis. Inflammation plays an important role in the development of ALS, and associated with rapid disease progression. Current observational studies indicate the thinning of cortical thickness in patients with ALS is associated with rapid disease progression and cognitive changes. However, the effects of inflammatory cytokines on cortical thickness in patients with ALS are unclear. Here, we investigated the relationship between inflammatory cytokines and cortical thickness in patients with ALS.

METHODS: We evaluated 51 patients with ALS for inflammatory cytokines including interleukin (IL)-4, interferon (IFN)-α, IL-1β, IL-2, IL-5, IL-12, tumor necrosis factor (TNF)-α, IL-6, IL-10, IL-8, IL-17, and IFN-γ and analyzed the correlation between these indicators and the ALS functional rating scale-revised (ALSFRS-R) score or disease progression rate (ΔFS score). Twenty-six patients with ALS and 26 controls were studied using whole-cortex analysis, and post-hoc analyses were performed to examine the correlation between brain cortical thickness and ALSFRS-R or ΔFS scores.

RESULTS: IL-4, IFN-α, IL-1β, and IL-2 levels were significantly correlated with ALSFRS-R scores, and the IL-2 level was significantly correlated with ΔFS scores. After controlling for age and sex, the ALS group had thinner cortexes in multiple clusters across the brain than the control group. Further analyses revealed that cortical thickness in the right superior temporal and lingual gyrus regions was inversely correlated with ΔFS scores. There was a significant positive correlation between the clusters in the right lingual cortex and IL-2 level.

CONCLUSION: These results suggest cortical thickness was reduced in patients with ALS in motor and non-motor cortical areas. Inflammatory factors (especially IL-2) were correlated with cortical thickness, and both were related to the disease progression rate, suggesting IL-2 plays an important role in ALS.}, } @article {pmid39839899, year = {2025}, author = {Goyal, MK and Goyal, O}, title = {Can Emax and platelet count truly differentiate between benign and malignant liver lesions?.}, journal = {World journal of gastroenterology}, volume = {31}, number = {3}, pages = {98758}, pmid = {39839899}, issn = {2219-2840}, mesh = {Humans ; *Liver Neoplasms/blood/diagnosis/pathology ; Platelet Count ; Diagnosis, Differential ; *Carcinoma, Hepatocellular/blood/diagnosis/pathology ; Nomograms ; *Liver/pathology ; Liver Cirrhosis/blood/diagnosis ; Predictive Value of Tests ; }, abstract = {This letter critically evaluates Jiang et al's article on the differentiation of benign and malignant liver lesions using Emax and platelet count. Despite notable findings, significant methodological and interpretative limitations are identified. The study lacks detailed assay conditions for Emax measurement, employs inadequate statistical methods without robust multivariate analysis, and does not provide clinically relevant threshold values. The nomogram's reliance on Emax as a major diagnostic contributor is questionable due to attenuation in hepatocellular carcinoma patients with cirrhosis. Moreover, the study's limitations, such as selection bias and confounding factors, are not adequately addressed. Future research should adopt more rigorous methodologies, including prospective studies with larger cohorts and standardized protocols for biomarker measurement, to enhance validity and clinical applicability.}, } @article {pmid39839897, year = {2025}, author = {Jiang, QR and Zeng, DW}, title = {Gut microbiota shifts in hepatitis B-related portal hypertension after transjugular intrahepatic portosystemic shunt: Mechanistic and clinical implications.}, journal = {World journal of gastroenterology}, volume = {31}, number = {3}, pages = {100752}, pmid = {39839897}, issn = {2219-2840}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Hypertension, Portal/microbiology/surgery/virology/etiology ; *Portasystemic Shunt, Transjugular Intrahepatic/adverse effects ; *Hepatic Encephalopathy/microbiology/etiology/diagnosis ; *Liver Cirrhosis/virology/microbiology/surgery ; Hepatitis B virus/pathogenicity ; *Hepatitis B/complications ; Dysbiosis ; }, abstract = {In this article, we provide commentary on the recent article by Zhao et al. We focus on the shifts in the gut microbiota of patients with hepatitis B virus (HBV)-associated cirrhosis/portal hypertension (PH) following transjugular intrahepatic portosystemic shunt (TIPS) and the implications for understanding the mechanisms, diagnosis, and treatment. By comparing the gut microbiota composition and dynamic changes before and after TIPS in patients with and without hepatic encephalopathy, the authors found an increase in non-probiotic bacteria in those who developed hepatic encephalopathy post-TIPS, with Morganella species present only in the hepatic encephalopathy group. The gut microbiota changes post-TIPS among patients without the occurrence of hepatic encephalopathy suggest potential therapeutic benefits through prophylactic microbiome therapies. Furthermore, the specific gut microbiota alterations may hold promise to predict the risk of hepatic encephalopathy in individuals undergoing TIPS for HBV-related PH. Despite these promising findings, future studies are needed to address limitations, including a small sample size, a relatively short evaluation period for gut microbiota alterations, the absence of data on dynamic alterations in gut microbiota post-TIPS and their correlation with blood ammonia levels, and the lack of validation in animal models. In conclusion, Zhao et al's study has shed new light on the link of gut microbiota with post-TIPS hepatic encephalopathy, potentially through the intricate gut-liver axis, and has important clinical implications for improving the management of patients with HBV-related PH.}, } @article {pmid39839311, year = {2024}, author = {Zhang, J and Li, Y and Shi, Q}, title = {Decremental response in patients with amyotrophic lateral sclerosis during repetitive nerve stimulation and its relationships with impaired homeostasis.}, journal = {Frontiers in aging neuroscience}, volume = {16}, number = {}, pages = {1502025}, pmid = {39839311}, issn = {1663-4365}, abstract = {BACKGROUND: Previous studies have suggested that neuromuscular junction (NMJ) denervation plays a critical role in amyotrophic lateral sclerosis (ALS). Repetitive nerve stimulation (RNS) has been used as a technique to test neuromuscular transmission, but the sensitivity and stability of its parameters have not been investigated in patients with ALS. In addition, the impact of impaired homeostasis on NMJ stability in patients with ALS remains unclear.

METHODS: A total of 421 patients with ALS were enrolled. Data on their clinical, biochemical and electrophysiological indicators were divided into a training set (collected from June 2019 to June 2022) and a test set (collected from July 2022 to June 2023). The coefficient of variation (CV) was used to assess the extent of variability. Stepwise regression was used in independent variable selection and model building.

RESULTS: In patients with ALS, area decrement had a higher rate of abnormal result and a lower CV than amplitude decrement. No significant difference in the rate of abnormal decrement was found when the first compound muscle action potential (CMAP) was compared with either the fourth or fifth one. Moreover, multivariate regression analysis suggests high-density lipoprotein cholesterol (HDL-C) had the greatest impact on decremental response, followed by serum uric acid (UA) and forced vital capacity (FVC). Females had a larger range of area decrement than males.

CONCLUSION: During RNS test, assessing area decrement significantly enhances our ability to detect the impairment of neuromuscular transmission in patients with ALS. Independent factors contributing to decremental response need to be considered in drug development and clinical trials targeting NMJ in patients with ALS.}, } @article {pmid39838960, year = {2025}, author = {Min, SM and Bashore, FM and Smith, JL and Havener, TM and Howell, S and Li, H and Couñago, RM and Popov, KI and Axtman, AD}, title = {Development of a Second-Generation, In Vivo Chemical Probe for PIKfyve.}, journal = {Journal of medicinal chemistry}, volume = {68}, number = {3}, pages = {3282-3308}, pmid = {39838960}, issn = {1520-4804}, support = {S10 OD032476/OD/NIH HHS/United States ; }, mesh = {Humans ; *Phosphoinositide-3 Kinase Inhibitors/pharmacology/chemistry/chemical synthesis/pharmacokinetics ; Animals ; Phosphatidylinositol 3-Kinases/metabolism ; Mice ; Morpholines/chemistry/pharmacokinetics/pharmacology/chemical synthesis ; Structure-Activity Relationship ; Crohn Disease/drug therapy ; COVID-19 Drug Treatment ; Molecular Probes/chemistry/pharmacokinetics ; Hydrazones ; Pyrimidines ; }, abstract = {We optimized our highly potent and cell-active chemical probe for phosphatidylinositol-3-phosphate 5-kinase (PIKfyve), SGC-PIKFYVE-1, resulting in compounds with improved potency and demonstrated in vivo stability. Use of an in-cell, kinome-wide selectivity panel allowed for confirmation of excellent in-cell selectivity of our lead compound, 40, and another promising analogue, 46. Evaluation of the pharmacokinetic (PK) profiles of these two compounds revealed that both are well tolerated systemically and orally bioavailable. Coupled with its subnanomolar cellular potency and impressive selectivity in cells, the long half-life of 40 makes it an ideal candidate for the evaluation of the consequences of PIKfyve inhibition in vivo. PIKfyve inhibition has been investigated clinically for indications including rheumatoid arthritis, Crohn's disease, COVID-19, and ALS using a single compound (apilimod), supporting the development of orthogonal PIKfyve inhibitors with in vivo stability.}, } @article {pmid39838927, year = {2025}, author = {Wang, Z and Sun, Y and Bai, Z and Li, M and Kong, D and Wu, G}, title = {Mitochondria-Related Genome-Wide Mendelian Randomization Identifies Putatively Causal Genes for Neurodegenerative Diseases.}, journal = {Movement disorders : official journal of the Movement Disorder Society}, volume = {40}, number = {4}, pages = {693-703}, doi = {10.1002/mds.30123}, pmid = {39838927}, issn = {1531-8257}, support = {SDQLQN2021-01//Qilu Young Scholars Program of Shandong University/ ; 202306352//Taishan Scholar Foundation of Shandong Province/ ; }, mesh = {Humans ; *Mendelian Randomization Analysis ; Genome-Wide Association Study ; *Neurodegenerative Diseases/genetics ; *Mitochondria/genetics/metabolism ; *Genetic Predisposition to Disease/genetics ; Quantitative Trait Loci/genetics ; }, abstract = {BACKGROUND: Mitochondrial dysfunction is increasingly recognized as a key factor in neurodegenerative diseases (NDDs), underscoring the therapeutic potential of targeting mitochondria-related genes. This study aimed to identify novel biomarkers and drug targets for these diseases through a comprehensive analysis that integrated genome-wide Mendelian randomization (MR) with genes associated with mitochondrial function.

METHODS: Using existing publicly available genome-wide association studies (GWAS) summary statistics and comprehensive data on 1136 mitochondria-related genes, we initially identified a subset of genes related to mitochondrial function that exhibited significant associations with NDDs. We then conducted colocalization and summary-data-based Mendelian randomization (SMR) analyses using expression quantitative trait loci (eQTL) to validate the causal role of these candidate genes. Additionally, we assessed the druggability of the encoded proteins to prioritize potential therapeutic targets for further exploration.

RESULTS: Genetically predicted levels of 10 genes were found to be significantly associated with the risk of NDDs. Elevated DMPK and LACTB2 levels were associated with increased Alzheimer's disease risk. Higher expression of NDUFAF2, BCKDK, and MALSU1, along with lower TTC19, raised Parkinson's disease risk. Higher ACLY levels were associated with both amyotrophic lateral sclerosis and multiple sclerosis (MS) risks, while decreased MCL1, TOP3A, and VWA8 levels raised MS risk. These genes primarily impact mitochondrial function and energy metabolism. Notably, several druggable protein targets identified are being explored for potential NDDs treatment.

CONCLUSIONS: This data-driven MR study demonstrated the causal role of mitochondrial dysfunction in NDDs. Additionally, this study identified candidate genes that could serve as potential pharmacological targets for the prevention and treatment of NDDs. © 2025 International Parkinson and Movement Disorder Society.}, } @article {pmid39838446, year = {2025}, author = {Ou, K and Jia, Q and Li, D and Li, S and Li, XJ and Yin, P}, title = {Application of antisense oligonucleotide drugs in amyotrophic lateral sclerosis and Huntington's disease.}, journal = {Translational neurodegeneration}, volume = {14}, number = {1}, pages = {4}, pmid = {39838446}, issn = {2047-9158}, mesh = {*Amyotrophic Lateral Sclerosis/drug therapy/genetics/therapy ; Humans ; *Huntington Disease/drug therapy/genetics/therapy ; *Oligonucleotides, Antisense/therapeutic use ; Animals ; *Genetic Therapy/methods ; *Neuroprotective Agents/therapeutic use ; }, abstract = {Amyotrophic lateral sclerosis (ALS) and Huntington's disease (HD) are diverse in clinical presentation and are caused by complex and multiple factors, including genetic mutations and environmental factors. Numerous therapeutic approaches have been developed based on the genetic causes and potential mechanisms of ALS and HD. Currently, available treatments for various neurodegenerative diseases can alleviate symptoms but do not provide a definitive cure. Gene therapy, which aims to modify or express specific proteins for neuroprotection or correction, is considered a powerful tool in managing neurodegenerative conditions. To date, antisense oligonucleotide (ASO) drugs targeting the pathological genes associated with ALS and HD have shown promising results in numerous animal studies and several clinical trials. This review provides a comprehensive overview of the development, mechanisms of action, limitations, and clinical applications of ASO drugs in neurodegenerative diseases, with a specific focus on ALS and HD therapeutic strategies.}, } @article {pmid39838017, year = {2025}, author = {McCaig, CD}, title = {Neurological Diseases can be Regulated by Phase Separation.}, journal = {Reviews of physiology, biochemistry and pharmacology}, volume = {187}, number = {}, pages = {273-338}, pmid = {39838017}, issn = {0303-4240}, mesh = {Humans ; Animals ; *Nervous System Diseases/physiopathology/metabolism ; Superoxide Dismutase/metabolism ; Motor Neuron Disease/physiopathology/metabolism ; Protein Aggregation, Pathological ; Phase Separation ; }, abstract = {Several neurological diseases arise from abnormal protein aggregation within neurones and this is closely regulated by phase separation. One such is motor neurone disease and aberrant aggregation of superoxide dismutase. Again these events are regulated by electrical forces that are examined.}, } @article {pmid39837582, year = {2025}, author = {Brubacher, LJ and Yellappa, V and Lestari, BW and Heitkamp, P and Aguilera Vasquez, N and Sassi, A and Olusola-Faleye, B and Thapa, P and Shyam Klinton, J and Sheokand, S and Pai, M and Oga-Omenka, C}, title = {Health and tuberculosis systems resilience, the role of the private sector and pandemic preparedness: insights from a cross-country qualitative study with policy-makers in India, Indonesia and Nigeria.}, journal = {BMJ global health}, volume = {10}, number = {1}, pages = {}, pmid = {39837582}, issn = {2059-7908}, support = {INV-022420/GATES/Gates Foundation/United States ; }, mesh = {Humans ; *COVID-19/epidemiology ; Indonesia/epidemiology ; *Tuberculosis/therapy/epidemiology ; India/epidemiology ; Nigeria/epidemiology ; Qualitative Research ; *Private Sector/organization & administration ; *Delivery of Health Care/organization & administration ; Pandemics ; *Administrative Personnel/psychology ; Health Policy ; SARS-CoV-2 ; Pandemic Preparedness ; }, abstract = {INTRODUCTION: The COVID-19 pandemic was an unprecedented challenge to health systems worldwide and had a severe impact on tuberculosis (TB) case notifications and service delivery. India, Indonesia and Nigeria are high TB-burden countries where the majority of initial care-seeking happens in the private health sector. The objectives of this study were to (1) explore policy-makers' perspectives on the impact of the COVID-19 pandemic on private sector TB service delivery in India, Indonesia and Nigeria and (2) identify cross-cutting insights for pandemic preparedness with respect to TB service delivery.

METHODS: From May to November 2021, 33 interviews were conducted with key policy-makers involved in health service administration, TB service delivery and/or the COVID-19 response in India, Indonesia and Nigeria (n=11 in each country). Interviews focused on the impact of COVID-19 on TB services and lessons learnt for pandemic preparedness with respect to TB in each study context. Data were analysed thematically using a hybrid inductive-deductive approach, informed by Haldane et al's Determinants of Health Systems Resilience Framework.

RESULTS: Policy-makers highlighted the crucial role of intersectoral collaboration, effective governance, innovative financing strategies, health workforce reallocation and technological advancements such as virtual consultations and mHealth in strengthening TB service delivery amid the COVID-19 pandemic. India relied on patient-provider support agencies to implement a joint strategy for TB care across sectors and states. Indonesia engaged networks of private provider professional associations to facilitate coordination of the COVID-19 response. Nigeria implemented a pandemic policy for public-private referral for the continuity of TB care.

CONCLUSIONS: Countries implemented varied measures to support TB service delivery during the COVID-19 pandemic. This study presents insights from three countries (India, Indonesia and Nigeria) that together offer a 'menu' of possibilities for supporting pandemic preparedness with respect to TB care vis-à-vis strengthening health systems resilience.}, } @article {pmid39837305, year = {2025}, author = {Tan, Y and Yang, T and Cheng, Y and Zhang, S and Xiao, Y and Liu, J and Shang, H}, title = {Association between Psychiatric Disorders and Amyotrophic Lateral Sclerosis: A Prospective Cohort Study from the UK Biobank.}, journal = {Neuroepidemiology}, volume = {}, number = {}, pages = {1-13}, doi = {10.1159/000543473}, pmid = {39837305}, issn = {1423-0208}, abstract = {INTRODUCTION: Psychiatric disorders have been reported to be associated with amyotrophic lateral sclerosis (ALS). However, evidence for the association remains inconsistent, and it is unclear whether specific categories of psychiatric disorders constitute risk factors for ALS. The study aimed to investigate the association between different categories of psychiatric disorders and the risk of ALS.

METHODS: We utilized data from the UK Biobank to conduct a population-based prospective cohort study. Cox proportional hazards models were employed to evaluate the association between a history of various psychiatric disorders including schizophrenia, bipolar disorder, depression, anxiety, stress-related disorders, and the risk of ALS. Analyses were adjusted for covariates including sociodemographic factors, lifestyle factors, and medical history.

RESULTS: Among the 484,065 participants initially included, 558 participants were diagnosed with ALS during a median follow-up of 13.63 years. With complete adjustment, previous schizophrenia (hazard ratio [HR] 6.32; 95% confidence interval [CI]: 2.60-15.36; p < 0.001) and depression (HR 1.37; 95% CI: 1.03-1.81; p = 0.03) were found to be significantly associated with ALS.

CONCLUSION: This large prospective cohort study indicated the association between schizophrenia, depression, and a higher risk of subsequent ALS. These findings suggest potential implications for early process of global neurodegeneration in ALS, underlining the need for further research to explore the underlying mechanisms.}, } @article {pmid39836386, year = {2025}, author = {Babu, S and Sharfstein, JM and Feldman, EL}, title = {Reimagining Care and Research for Amyotrophic Lateral Sclerosis.}, journal = {JAMA neurology}, volume = {82}, number = {6}, pages = {535-536}, doi = {10.1001/jamaneurol.2024.4757}, pmid = {39836386}, issn = {2168-6157}, } @article {pmid39836043, year = {2025}, author = {Berry, JD and Hagan, M and Zhang, J and Liu, Y and Ciepielewska, M}, title = {Longer disease progression milestone-free time in people with amyotrophic lateral sclerosis treated versus not treated with intravenous edaravone: results from an administrative claims analysis.}, journal = {Journal of comparative effectiveness research}, volume = {14}, number = {2}, pages = {e240007}, pmid = {39836043}, issn = {2042-6313}, mesh = {Humans ; *Edaravone/administration & dosage/therapeutic use ; *Amyotrophic Lateral Sclerosis/drug therapy ; Male ; Female ; Retrospective Studies ; Middle Aged ; Disease Progression ; Aged ; Administration, Intravenous ; *Free Radical Scavengers/therapeutic use/administration & dosage ; }, abstract = {Aim: To estimate time-to-progression milestones in people with amyotrophic lateral sclerosis (PALS) treated versus not treated with intravenous (IV) edaravone (Radicava[®] IV, Mitsubishi Tanabe Pharma America [MTPA], hereafter "IV edaravone") in a real-world setting. Background: IV edaravone is US FDA approved for the treatment of ALS and was shown in clinical trials to slow the rate of physical functional decline. Patients & methods: This retrospective observational analysis included PALS continuously enrolled in Optum's Clinformatics[®] Data Mart between 8 August 2017 and 31 December 2021. Cases treated with IV edaravone and controls not treated with IV edaravone were propensity score matched for: age, sex, race, US region of residence, pre-index disease duration, insurance, riluzole prescription; and pre-index claims for cardiovascular disease, artificial nutrition/gastrostomy tube, noninvasive ventilation and all-cause hospitalization. The index date was the first IV edaravone claim for cases; for controls, the index date was randomly assigned after IV edaravone market availability. Restricted mean time lost was calculated for the following disease progression milestones: new use of canes/walkers/wheelchairs, artificial nutrition, noninvasive ventilation, invasive ventilation, speech-generating devices and hospice. Results: Cases (n = 395) were matched to controls (n = 395). Cases had less restricted mean time lost, indicating longer disease progression milestone-free time, for all disease progression milestones. From 0 to 24 months post index, more cases (n = 129) than controls (n = 103) reported no milestones and more controls (n = 232) than cases (n = 131) reported deaths. Conclusion: In a US-based real-world setting, IV edaravone-treated PALS had a longer time to disease progression milestone events and fewer deaths in 2 years compared with PALS not treated with IV edaravone.}, } @article {pmid39835561, year = {2025}, author = {Rai, A and Shukla, S and Gupta, RK and Mishra, A}, title = {ALS: A Silent Slayer of Motor Neurons. Traditional Chinese Herbal Medicine as an Effective Therapy.}, journal = {Current pharmaceutical design}, volume = {31}, number = {17}, pages = {1328-1346}, pmid = {39835561}, issn = {1873-4286}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy ; *Drugs, Chinese Herbal/therapeutic use/pharmacology ; *Neuroprotective Agents/therapeutic use/pharmacology ; *Motor Neurons/drug effects/pathology ; *Medicine, Chinese Traditional ; Animals ; }, abstract = {Amyotrophic lateral sclerosis (ALS), is a progressive neurodegenerative disease characterized by motor symptoms, and cognitive impairment. The complexity in treating ALS arises from genetic and environmental factors, contributing to the gradual decline of lower and upper motor neurons. The anticipated pharmaceutical market valuation for ALS is projected to reach $1,038.94 million by 2032. This projection underscores the escalating impact of ALS on global healthcare systems. ALS prevalence is expected to surge to 376,674 cases by 2040. In 2022, India ranked among the top 3 Asian-Pacific nations, while North America dominated the global ALS market. Ongoing investigations explore the potential of neuroprotective drugs like riluzole and edaravone in ALS treatment. Recently approved drugs, Relyvrio (sodium phenylbutyrate and taurursodiol) and Tofersen (Qalsody) have completed the trials, and others are currently undergoing extensive clinical trials. Continuous research and exploration of therapeutic avenues, including gene therapy and neuroprotective treatments, are imperative to address the challenges posed by ALS and other neurodegenerative diseases. Traditional Chinese medicine (TCM) approaches and clinical trials are being explored for treating ALS symptoms, targeting neuroinflammation, oxidative damage, and muscle weakness, showcasing the potential benefits of integrating traditional and modern approaches in ALS management.}, } @article {pmid39835009, year = {2024}, author = {Frolov, A and D'sa, E and Henderson, C and Guzman, MA and Hayat, G and Martin, JR}, title = {Complex Genetic Framework in Familial Amyotrophic Lateral Sclerosis With a C9ORF72 Mutation: A Case Report.}, journal = {Cureus}, volume = {16}, number = {12}, pages = {e76027}, pmid = {39835009}, issn = {2168-8184}, abstract = {A significantly diverse clinical presentation of amyotrophic lateral sclerosis (ALS), even in its best-studied familial form, continues to hinder current efforts to develop effective disease-modifying drugs for the cure of this rapidly progressive, fatal neuromuscular disease. We have previously shown that clinical heterogeneity of sporadic ALS (sALS) could be explained, at least in part, by its polygenic nature as well as by the presence of mutated genes linked to non-ALS neurological diseases and genes known to mediate ALS-related pathologies. We hypothesized that a similar genetic framework could also be present in patients with familial ALS (fALS). To test this hypothesis, we conducted post-mortem genetic screening of an individual with fALS and a mutation in the C9ORF72 gene. C9ORF72 mutations are highly penetrant and are present in the majority of fALS patients. Genetic screening by whole exome sequencing (WES) on the next generation sequencing (NGS) Illumina platform (San Diego, CA, USA) followed by examination of the respective rare (minor allele frequency (MAF) ≤ 0.01) pathological/deleterious genetic variants yielded results consistent with our hypothesis of the presence of a complex genetic framework in fALS. Additional members of this genetic framework were identified when the low-frequency (0.01 < MAF < 0.05) pathological/deleterious genetic variants were analyzed with the low-frequency biallelic AHNAK2, GLI3, PTIRM1, and ZNF254 variants, warranting a closer look at their potentially important role in fALS as C9ORF72 genetic modifiers as well as their link to both neuromuscular disorders/ALS and cancer. Therefore, in addition to the current genetic screening using a standard panel of ALS-related genes, a supplementary screening by WES could be very beneficial for the development of personalized treatment of ALS patients as well as in search of the respective efficient disease-modifying drugs.}, } @article {pmid39834554, year = {2025}, author = {Sarallah, R and Jahani, S and Soltani Khaboushan, A and Moaveni, AK and Amiri, M and Majidi Zolbin, M}, title = {The role of CXCL12/CXCR4/CXCR7 axis in cognitive impairment associated with neurodegenerative diseases.}, journal = {Brain, behavior, & immunity - health}, volume = {43}, number = {}, pages = {100932}, pmid = {39834554}, issn = {2666-3546}, abstract = {Neurodegenerative diseases, including Alzheimer's Disease (AD), Parkinson's Disease (PD), Multiple Sclerosis (MS), and Amyotrophic Lateral Sclerosis (ALS), are characterized by progressive neuronal loss and cognitive impairment (CI). The: Cysteine-X-cysteine chemokine ligand 12(CXCL12)/CXC chemokine receptor type 4 (CXCR4)/CXC chemokine receptor type 7 (CXCR7) axis has emerged as a critical molecular pathway in the development of CI in these disorders. This review explores the role of this axis in the pathogenesis of CI across these neurodegenerative diseases, synthesizing current evidence and its implications for targeted therapies. In AD, dysregulation of this axis contributes to amyloid-β accumulation and tau hyperphosphorylation, leading to synaptic dysfunction and cognitive decline. PD studies reveal that CXCL12/CXCR4 signaling influences dopaminergic neuron survival and microglial activation, affecting cognitive function. In MS, the axis modulates neuroinflammation and demyelination processes, impacting cognitive performance. ALS research indicates that the CXCL12/CXCR4/CXCR7 pathway is involved in motor neuron degeneration and associated cognitive deficits. Across these diseases, the axis influences neuroinflammation, synaptic plasticity, and neuronal survival through various signaling cascades, including PI3K/AKT, MAPK, and JAK/STAT pathways. Emerging evidence suggests that modulating this axis could provide neuroprotective effects and potentially alleviate cognitive symptoms. This review highlights the potential of the CXCL12/CXCR4/CXCR7 axis as a therapeutic target for addressing CI in neurodegenerative diseases. It also underscores the need for further research to fully elucidate its role and develop effective interventions, potentially leading to improved clinical management strategies for these devastating disorders.}, } @article {pmid39834320, year = {2025}, author = {Lero, CM and Park, S and Mroz, EL}, title = {Mapping the evidence of self-compassion in caregiver wellbeing for caregivers of persons with neurodegenerative disease: A scoping review.}, journal = {Palliative & supportive care}, volume = {23}, number = {}, pages = {e38}, doi = {10.1017/S1478951524001639}, pmid = {39834320}, issn = {1478-9523}, mesh = {Humans ; *Caregivers/psychology ; *Empathy ; *Neurodegenerative Diseases/psychology/complications ; }, abstract = {OBJECTIVES: Caregivers of those with neurodegenerative disease (ND) manage complex symptoms which impact their wellbeing. Self-compassion can promote maintenance of wellbeing during challenging experiences, including caregiving. Little guidance exists for observationally studying self-compassion or targeted interventions for this population. Our objective was to complete a scoping review of research describing self-compassion in the context of caregiver wellbeing of caregivers of those living with ND.

METHODS: Following Preferred Reporting Items for Systematic Reviews and Meta-analysis extension for Scoping Reviews (PRISMA-ScR) guidelines, 3 online databases identified 350 peer-reviewed articles, 18 of which were included in this study. Eligibility included being written in English, targeting caregivers of those living with ND, and examination of self-compassion. Articles were organized by the incorporation or characterization of self-compassion in the study design.

RESULTS: Alzheimer's disease predominated study samples of care recipients. Across study types self-compassion appeared as a theoretical concept, emerging theme, variable associated with other outcomes, and main outcome variable. Self-compassion is frequently measured using the Self-Compassion Scale, full or short form .

SIGNIFICANCE OF RESULTS: The study of self-compassion with caregivers of individuals living with ND is growing. Current literature is somewhat unfocussed, leading to gaps in understanding conceptualization to achieve maximum intervention benefits. Clarifying the role of self-compassion in caregiver wellbeing will provide a lens through which non-pharmacologic, psychotherapeutic, and behavioral intervention development may be framed to reduce negative psychological outcomes. The most frequently represented ND is Alzheimer's disease or other dementia, obscuring other NDs like amyotrophic lateral sclerosis, Parkinson's disease, and others.}, } @article {pmid39834142, year = {2025}, author = {Stikvoort García, DJL and van den Berg, LH and Sleutjes, BTHM and Goedee, HS}, title = {Diagnostic Accuracy of Median Nerve Cross-Sectional Area in Suspected Amyotrophic Lateral Sclerosis.}, journal = {Muscle & nerve}, volume = {71}, number = {4}, pages = {680-684}, pmid = {39834142}, issn = {1097-4598}, support = {//Stichting ALS Nederland/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnostic imaging/diagnosis/physiopathology ; Male ; Female ; Middle Aged ; *Median Nerve/diagnostic imaging/pathology ; Aged ; Prospective Studies ; Ultrasonography ; Adult ; ROC Curve ; Retrospective Studies ; }, abstract = {INTRODUCTION/AIMS: Reduced nerve sizes obtained by nerve ultrasound (NUS) have been proposed as a potential diagnostic marker for amyotrophic lateral sclerosis (ALS). However, prospective studies evaluating patients with suspected ALS are currently lacking. We, therefore, evaluated the diagnostic accuracy of a standardized NUS protocol in a large sample of suspected ALS patients.

METHODS: We prospectively recruited 193 patients with suspected ALS, all of whom underwent the relevant ancillary tests. They also underwent a standardized NUS protocol, evaluating median nerve cross-sectional area (CSA) at upper arm, forearm and wrist. Additionally, we selected, retrospectively, a random sample of incident patients with multifocal motor neuropathy (MMN, n = 42). We determined diagnostic accuracy using receiver operating characteristic (ROC) analysis.

RESULTS: Ultimately, 143/193 patients received a final diagnosis of ALS, at a median disease duration of 10 months. Fifty patients were classified as non-ALS. Diagnostic yield of NUS to distinguish between patients with and without ALS was low (highest area under the curve (AUC) at the wrist: 0.57). In contrast, abnormal nerve sizes accurately discriminated MMN from patients with ALS, with AUCs ranging from 0.65 at the wrist to 0.86 at the upper arm.

DISCUSSION: Our study shows that reductions in nerve size are unlikely to have diagnostic utility during routine evaluation of suspected patients with ALS. However, when the differential diagnosis includes both ALS and MMN, median nerve size demonstrates high diagnostic accuracy.}, } @article {pmid39833708, year = {2025}, author = {Bidarolli, M and Das, B and Rawat, VS and Manocha, S and Sony, HT and Agnihotri, A and Gupta, M and Agera, F}, title = {Polypharmacy and anticholinergic burden scales in older adults: a cross-sectional study among psychiatric outpatients in a tertiary care hospital.}, journal = {BMC geriatrics}, volume = {25}, number = {1}, pages = {43}, pmid = {39833708}, issn = {1471-2318}, mesh = {Humans ; Male ; Cross-Sectional Studies ; Female ; *Polypharmacy ; Aged ; *Cholinergic Antagonists/adverse effects/therapeutic use ; Middle Aged ; Tertiary Care Centers ; *Mental Disorders/drug therapy/epidemiology ; India/epidemiology ; Outpatients/psychology ; Aged, 80 and over ; *Psychotropic Drugs/adverse effects/therapeutic use ; }, abstract = {INTRODUCTION: Mental disorders are prevalent among older adults, often leading to the use of multiple medications, many with anticholinergic properties. Polypharmacy, common in this population, is a major contributor to anticholinergic burden, which is linked to cognitive and physical decline. This study investigates the relationship between polypharmacy and anticholinergic burden across seven anticholinergic burden scales in elderly patients attending the psychiatric outpatient.

METHODS: Study was conducted at a psychiatry outpatient clinic at All India Institute of Medical Sciences, Rishikesh, India, from December 2021 to March 2023. Elderly patients (aged ≥ 60 years) who were on at least one psychotropic medication and had a primary working diagnosis of psychiatric illness were included. All psychotropic medications, including antidepressants, antipsychotics, mood stabilizers, and hypnotics, were evaluated. Anticholinergic burden scales were calculated by the respective tools. Univariate analysis was adopted to determine the factors that may affect polypharmacy.

RESULTS: Study included 1165 elderly patients aged ≥ 60 years. The prevalence of polypharmacy was 20.43% (n = 238). Clonazepam (n = 364, 17.28%), escitalopram (n = 197, 9.35%), metformin (n = 165, 7.83%), sertraline (n = 141, 6.69%), mirtazapine (n = 129, 6.12%), and lorazepam (n = 110, 5.22%) were among the most frequently prescribed anticholinergic drugs. Univariate analysis demonstrated that all anticholinergic risk assessment scales were closely correlated with polypharmacy, with the strongest association observed for the Anticholinergic Load Scale (ALS) (Odds Ratio = 4.3; p < 0.001). Polypharmacy was also positively associated with adverse drug reactions (Odds Ratio = 1.81; 95% Confidence Interval = 1.27-2.56).

CONCLUSION: The anticholinergic burden in this cohort of elderly psychiatry patients was high, with 95.1% (n = 1108) experiencing a significant burden. Adverse drug events and anticholinergic burden scales were positively associated with polypharmacy, with a stronger correlation between polypharmacy and ALS scores than with other anticholinergic burden scales in older adults.}, } @article {pmid39832811, year = {2025}, author = {Ghaderi, S and Mohammadi, S and Ahmadzadeh, AM and Darmiani, K and Arab Bafrani, M and Jashirenezhad, N and Helfi, M and Alibabaei, S and Azadi, S and Heidary, S and Fatehi, F}, title = {Thalamic Magnetic Susceptibility (χ) Alterations in Neurodegenerative Diseases: A Systematic Review and Meta-Analysis of Quantitative Susceptibility Mapping Studies.}, journal = {Journal of magnetic resonance imaging : JMRI}, volume = {62}, number = {1}, pages = {271-294}, doi = {10.1002/jmri.29698}, pmid = {39832811}, issn = {1522-2586}, mesh = {Humans ; *Brain Mapping/methods ; Iron/metabolism ; *Magnetic Resonance Imaging/methods ; *Neurodegenerative Diseases/diagnostic imaging ; *Thalamus/diagnostic imaging ; }, abstract = {BACKGROUND: Quantitative Susceptibility Mapping (QSM) provides a non-invasive post-processing method to investigate alterations in magnetic susceptibility (χ), reflecting iron content within brain regions implicated in neurodegenerative diseases (NDDs).

PURPOSE: To investigate alterations in thalamic χ in patients with NDDs using QSM.

STUDY TYPE: Systematic review and meta-analysis.

POPULATION: A total of 696 patients with NDDs and 760 healthy controls (HCs) were included in 27 studies.

FIELD STRENGTH/SEQUENCE: Three-dimensional multi-echo gradient echo sequence for QSM at mostly 3 Tesla.

ASSESSMENT: Studies reporting QSM values in the thalamus of patients with NDDs were included. Following PRISMA 2020, we searched the four major databases including PubMed, Scopus, Web of Science, and Embase for peer-reviewed studies published until October 2024.

STATISTICAL TESTS: Meta-analysis was conducted using a random-effects model to calculate the standardized mean difference (SMD) between patients and HCs.

RESULTS: The pooled SMD indicated a significant increase in thalamic χ in NDDs compared to HCs (SMD = 0.42, 95% CI: 0.05-0.79; k = 27). Notably, amyotrophic lateral sclerosis patients showed a significant increase in thalamic χ (1.09, 95% CI: 0.65-1.53, k = 2) compared to HCs. Subgroup analyses revealed significant χ alterations in younger patients (mean age ≤ 62 years; 0.56, 95% CI: 0.10-1.02, k = 11) and studies using greater coil channels (coil channels > 16; 0.64, 95% CI: 0.28-1.00, k = 9). Publication bias was not detected and quality assessment indicated that studies with a lower risk of bias presented more reliable findings (0.75, 95% CI: 0.32-1.18, k = 9). Disease type was the primary driver of heterogeneity, while other factors, such as coil type and geographic location, also contributed to variability.

DATA CONCLUSION: Our findings support the potential of QSM for investigating thalamic involvement in NDDs. Future research should focus on disease-specific patterns, thalamic-specific nucleus analysis, and temporal evolution.

PLAIN LANGUAGE SUMMARY: Our research investigated changes in iron levels within the thalamus, a brain region crucial for motor and cognitive functions, in patients with various neurodegenerative diseases (NDDs). The study utilized a specific magnetic resonance imaging technique called Quantitative Susceptibility Mapping (QSM) to measure iron content. It identified a significant increase in thalamic iron levels in NDD patients compared to healthy individuals. This increase was particularly prominent in patients with Amyotrophic Lateral Sclerosis, younger individuals, and studies employing advanced imaging equipment.

LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 2.}, } @article {pmid39831450, year = {2025}, author = {Hoehne, SN and Cary, JA and Bailey, LN and Davidow, EB and Martin, LG and DeJong, TL}, title = {An exploratory study on the effect of rescuer team size on basic and advanced life support technical skills in a high-fidelity simulation of canine cardiopulmonary arrest.}, journal = {Journal of veterinary emergency and critical care (San Antonio, Tex. : 2001)}, volume = {35}, number = {1}, pages = {9-18}, pmid = {39831450}, issn = {1476-4431}, support = {//Converse Fund, Washington State University College of Veterinary Medicine 2021-2022 CVM Intramural Research Grants/ ; }, mesh = {Animals ; Dogs ; *Cardiopulmonary Resuscitation/veterinary ; *Heart Arrest/veterinary/therapy ; Prospective Studies ; *Dog Diseases/therapy ; Clinical Competence ; *Advanced Cardiac Life Support/veterinary ; Humans ; }, abstract = {OBJECTIVE: To evaluate the effect of rescuer team size on objective skill measures of basic life support (BLS) and advanced life support (ALS) using high-fidelity canine CPR simulation.

DESIGN: Prospective, experimental study.

SETTING: Veterinary clinical simulation center.

SUBJECTS: Forty-eight Reassessment Campaign on Veterinary Resuscitation CPR-certified veterinary students.

MEASUREMENTS AND MAIN RESULTS: Five groups of participants each conducted 3 CPR simulations in configurations of 4, 6, and 8 rescuers. Simulations represented a shock patient declining into asystole, followed by ventricular fibrillation and return of spontaneous circulation. Resuscitation efforts were video-recorded to evaluate BLS and ALS tasks. Mean (±SD) was derived and data were compared among team sizes using ANOVA and Tukey's post hoc analysis. Significance was set at P < 0.05. Among teams of 4, 6, and 8 rescuers, time to first chest compression (13 s [±6], 9 s [±2], 8 s [±4]; P = 0.24) and positive-pressure breath (101 s [±37], 56 s [±15], 67 s [±24]; P = 0.05) were not significantly different. Chest compression (100/min [±5], 108/min [±6], 107/min [±6]; P = 0.12) and ventilatory rates (9/min [±1], respectively, P = 0.52) were not significantly different. Time without chest compressions/total length of CPR was not significantly different (72 s [±16], 61 s [±16], 54 s [±8]; P = 0.15). Capnography and ECG monitoring were used by all teams. Time to first vasopressor administration was significantly different among team sizes (268 s [±70], 164 s [±65], 174 s [±34]; P = 0.04), with vasopressors being most quickly administered by teams of 6 rescuers. Time to electrical defibrillation was not significantly different (486 s [±45], 424 s [±22], 488 s [±181]; P = 0.57). Incorrect ALS interventions occurred in 60%, 0%, and 40% of CPR events in 4, 6, and 8 rescuer teams, respectively.

CONCLUSIONS: Although the achievement of BLS tasks was comparable in teams of 4 rescuers, teams of 6 rescuers may be preferable based on differences in the rate of guideline-incompliant treatments and ALS task efficiency. Teams of 8 rescuers were neither more efficient nor more accurate at conducting BLS and ALS tasks.}, } @article {pmid39831399, year = {2025}, author = {Wang, F and Jing, Z and Wang, Q and Li, M and Lu, B and Huo, A and Zhao, C and Zhou, H and Liang, W and Hu, W and Fu, X}, title = {Bidirectional Mendelian Randomization Analysis of the Association Between Mitochondrial Proteins and Neurodegenerative Diseases.}, journal = {Brain and behavior}, volume = {15}, number = {1}, pages = {e70283}, pmid = {39831399}, issn = {2162-3279}, support = {82303029//National Natural Science Foundation of China/ ; 2024YLZDJH027//the Zhengzhou Science and Technology Innovation Project for Healthcare/ ; YXKC2022020//Health Commission of Henan Province/ ; 232102311134//Science and Technology Department of Henan Province/ ; }, mesh = {Humans ; *Mendelian Randomization Analysis/methods ; *Neurodegenerative Diseases/genetics/metabolism ; *Mitochondrial Proteins/genetics/metabolism ; Genome-Wide Association Study ; Genetic Predisposition to Disease ; }, abstract = {BACKGROUND: Neurodegenerative diseases involve progressive neuronal dysfunction and cognitive decline, posing substantial global challenges. Although the precise causes remain unclear, several studies highlight the role of protein metabolism abnormalities in disease development. This study investigates the causal links between variations in mitochondrial protein genes and neurodegenerative diseases, aiming to elucidate their potential contributions to disease progression and identify novel therapeutic strategies.

METHODS: Herein, we utilized data from genome-wide association studies (GWAS) on mitochondrial proteins and neurodegenerative diseases. Bidirectional Mendelian randomization (MR), employing instrumental variables (IVs), was used to assess causal relationships. The primary method for estimating causal effects was the inverse variance-weighted (IVW) method, supplemented by additional MR approaches.

RESULTS: Bidirectional MR revealed significant associations between mitochondrial protein gene variants and neurodegenerative diseases. Specifically, associations were found with Alzheimer's disease (AD) (three proteins), Parkinson's disease (PD) (four proteins), amyotrophic lateral sclerosis (ALS) (six proteins), multiple sclerosis (two proteins), and dementia with Lewy bodies (four proteins). Conversely, analyses indicated significant associations of neurodegenerative diseases with mitochondrial protein gene variants, notably with AD, dementia with Lewy bodies, and multiple sclerosis, affecting multiple mitochondrial protein levels. Bidirectional causality was observed between dementia with Lewy bodies and C21orf33.

CONCLUSIONS: Using MR, we identified significant links between mitochondrial protein gene mutations and the risk of neurodegenerative diseases. These results highlight reciprocal relationships where certain neurodegenerative diseases influence mitochondrial protein expression levels. These findings underscore the pivotal role of mitochondrial proteins in neurodegenerative diseases, offering critical insights into disease mechanisms and potential therapeutic avenues.}, } @article {pmid39831374, year = {2025}, author = {Risi, B and Imarisio, A and Cuconato, G and Padovani, A and Valente, EM and Filosto, M}, title = {Mitochondrial DNA (mtDNA) as fluid biomarker in neurodegenerative disorders: A systematic review.}, journal = {European journal of neurology}, volume = {32}, number = {1}, pages = {e70014}, pmid = {39831374}, issn = {1468-1331}, mesh = {Humans ; Alzheimer Disease/cerebrospinal fluid/blood ; Amyotrophic Lateral Sclerosis/cerebrospinal fluid/blood ; Biomarkers/cerebrospinal fluid/blood ; *DNA, Mitochondrial/cerebrospinal fluid/blood ; *Neurodegenerative Diseases/cerebrospinal fluid/blood/genetics/diagnosis ; Parkinson Disease/cerebrospinal fluid/blood ; }, abstract = {BACKGROUND: Several studies evaluated peripheral and cerebrospinal fluid (CSF) mtDNA as a putative biomarker in neurodegenerative diseases, often yielding inconsistent findings. We systematically reviewed the current evidence assessing blood and CSF mtDNA levels and variant burden in Parkinson's disease (PD), Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS). Multiple sclerosis (MS) was also included as a paradigm of chronic neuroinflammation-driven neurodegeneration.

METHODS: Medline, Embase, Scopus and Web of Science were searched for articles published from inception until October 2023. Studies focused on mtDNA haplogroups or hereditary pathogenic variants were excluded. Critical appraisal was performed using the Quality Assessment for Diagnostic Accuracy Studies criteria.

RESULTS: Fifty-nine original studies met our a priori-defined inclusion criteria. The majority of CSF-focused studies showed (i) decreased mtDNA levels in PD and AD; (ii) increased levels in MS compared to controls. No studies evaluated CSF mtDNA in ALS. Results focused on blood cell-free and intracellular mtDNA were contradictory, even within studies evaluating the same disease. This poor reproducibility is likely due to the lack of consideration of the many factors known to affect mtDNA levels. mtDNA damage and methylation levels were increased and reduced in patients compared to controls, respectively. A few studies investigated the correlation between mtDNA and disease severity, with conflicting results.

CONCLUSIONS: Additional well-designed studies are needed to evaluate CSF and blood mtDNA profiles as putative biomarkers in neurodegenerative diseases. The identification of "mitochondrial subtypes" of disease may enable novel precision medicine strategies to counteract neurodegeneration.}, } @article {pmid39831022, year = {2025}, author = {Okpete, UE and Byeon, H}, title = {Brain-derived neurotrophic factor alterations and cognitive decline in schizophrenia: Implications for early intervention.}, journal = {World journal of psychiatry}, volume = {15}, number = {1}, pages = {102131}, pmid = {39831022}, issn = {2220-3206}, abstract = {This manuscript explores the recent study by Cui et al which assessed the interplay between inflammatory cytokines and brain-derived neurotrophic factor (BDNF) levels in first-episode schizophrenia patients. The study revealed that higher levels of interleukin-6 and tumor necrosis factor-α correlated with reduced BDNF levels and poorer cognitive performance. Schizophrenia is a severe psychiatric disorder impacting approximately 1% of the global population, characterized by positive symptoms (hallucinations and delusions), negative symptoms (diminished motivation and cognitive impairments) and disorganized thoughts and behaviors. Emerging research highlights the role of BDNF as a potential biomarker for early diagnosis and therapeutic targeting. The findings from Cui et al's study suggest that targeting neuroinflammation and enhancing BDNF levels may improve cognitive outcomes. Effective treatment approaches involve a combination of pharmacological and non-pharmacological interventions tailored to individual patient needs. Hence, monitoring cognitive and neuroinflammatory markers is essential for improving patient outcomes and quality of life. Consequently, this manuscript highlights the need for an integrated approach to schizophrenia management, considering both clinical symptoms and underlying neurobiological changes.}, } @article {pmid39829394, year = {2025}, author = {Buddenhagen, CE and Ngow, Z and Wynne-Jones, B and Rolston, MP}, title = {Resistance to the herbicides haloxyfop and iodosulfuron is common in commercial ryegrass (Lolium) seed lines.}, journal = {Pest management science}, volume = {81}, number = {6}, pages = {2990-2996}, pmid = {39829394}, issn = {1526-4998}, support = {//AgResearch Ltd via its contribution to the Better Border Biosecurity (B3) research collaboration, www.b3nz.org/ ; }, mesh = {*Lolium/drug effects/genetics/growth & development ; *Herbicides/pharmacology ; *Herbicide Resistance/genetics ; Seeds/drug effects/genetics/growth & development ; *Sulfonylurea Compounds/pharmacology ; *Halogenated Diphenyl Ethers/pharmacology ; *Sulfonamides/pharmacology ; New Zealand ; Glycine/analogs & derivatives/pharmacology ; Pyridines ; }, abstract = {BACKGROUND: Ryegrass (Lolium spp.) is a key forage providing a $14 billion contribution to New Zealand's gross domestic product (GDP). However, ryegrass can also act as a weed and evolve resistance to herbicides used for its control. Farmers suspected that imported seed might contribute to resistance issues. Herbicide resistance frequencies were investigated in commercial ryegrass seed lines intended for multiplication in New Zealand. Samples from 56 basic seed lots and 52 unique cultivars sourced from regions including New Zealand, United States, Europe and Japan were planted in field trials. Seedlings were then sprayed with three common herbicides: glyphosate, iodosulfuron, and haloxyfop. Surviving plants were retested to confirm resistance.

RESULTS: Resistance to haloxyfop and or iodosulfuron was detected in 79% of seed lines. However, frequencies were not significantly higher in imported lines (from United States and Europe) compared with New Zealand lines. Resistance was detected at frequencies between 0.00112% and 10% for haloxyfop and between 0.00212% and 14.28% for iodosulfuron Resistance to glyphosate was not found. There was no significant difference between the resistance detected in seed samples sourced from different seed companies.

CONCLUSIONS: It was found that 63% of resistant lines had resistance frequencies rarer than 0.1%, but this is potentially problematic considering typical sowing rates. Imported versus domestic seed sources were not significantly different; they pose similar levels of resistance risk to farmers. Lolium multiflorum had a higher resistance frequency compared to Lolium perenne (although only six L. multiflorum lots were evaluated). Breeders should screen progeny of early crosses for herbicide resistance. © 2025 The Author(s). Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.}, } @article {pmid39829368, year = {2025}, author = {Bedlack, R}, title = {Stitching strength: things I've learned about hope and how I am trying to weave them into my in ALS practice.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {26}, number = {3-4}, pages = {189-191}, doi = {10.1080/21678421.2025.2454903}, pmid = {39829368}, issn = {2167-9223}, } @article {pmid39829311, year = {2025}, author = {Falanga, AP and Piccialli, I and Greco, F and D'Errico, S and Nolli, MG and Borbone, N and Oliviero, G and Roviello, GN}, title = {Nanostructural Modulation of G-Quadruplex DNA in Neurodegeneration: Orotate Interaction Revealed Through Experimental and Computational Approaches.}, journal = {Journal of neurochemistry}, volume = {169}, number = {1}, pages = {e16296}, pmid = {39829311}, issn = {1471-4159}, support = {IR0000010 "ELIXIRxNextGenIT"//European Commission/ ; PNRRMUR-M4C2-I//European Commission/ ; FOE 2020-ISBE-IT Joint Research Unit//Ministero dell'Università e della Ricerca/ ; }, mesh = {*G-Quadruplexes/drug effects ; Humans ; *DNA/chemistry/metabolism ; Molecular Docking Simulation/methods ; *Neurodegenerative Diseases/metabolism/genetics ; *Nanostructures/chemistry ; }, abstract = {The natural compound orotic acid and its anionic form, orotate, play a pivotal role in various biological processes, serving as essential intermediates in pyrimidine de novo synthesis, with demonstrated connections to dietary, supplement, and neurodrug applications. A novel perspective on biomolecular aggregation at the nanoscale, particularly pertinent to neurodegeneration, challenges the established paradigm positing that peptide (amyloid beta) and protein (tau) aggregation mainly govern the molecular events underlying prevalent neuropathologies. Emerging biological evidence indicates a notable role for G-quadruplex (G4) DNA aggregation in neurodegenerative processes affecting neuronal cells, particularly in the presence of extended (G4C2)n repeats in nuclear DNA sequences. Our study concerns d[(GGGGCC)3GGGG], a G4-forming DNA model featuring G4C2 repeats that is in correlation with neurodegeneration. Through different investigations utilizing spectroscopic techniques (CD, UV, and thermal denaturations), PAGE electrophoresis, and molecular docking, the study explores the influence of orotate on the aggregation of this neurodegeneration-associated DNA. A computational approach was employed to construct an in silico model of the DNA aggregate, which involved the docking of multiple G4 units and subsequent integration of the ligand into both the DNA monomer and its in silico aggregated model. The convergence of computational analyses and empirical data collectively supports the hypothesis that orotate possesses the capability to modulate the aggregation of neurodegeneration-related DNA. Notably, the findings suggest the potential utility of orotate as a neurodrug, especially for the therapy of amyotrophic lateral sclerosis (ALS) and Frontotemporal Dementia (FTD), with its current status as a dietary supplement indicating minimal safety concerns. Additionally, orotate demonstrated a slight increase in mitochondrial dehydrogenase activity as assessed by the MTT assay, which is beneficial for a neurodrug as it suggests a potential role in enhancing mitochondrial function and supporting neuronal health.}, } @article {pmid39828328, year = {2025}, author = {Yorimoto, K and Ariake, Y and Kawaguchi, T and Hara, T}, title = {Long-term lung volume recruitment therapy maintains ventilator weaning in a patient with ALS following tracheostomy.}, journal = {BMJ case reports}, volume = {18}, number = {1}, pages = {}, doi = {10.1136/bcr-2024-262945}, pmid = {39828328}, issn = {1757-790X}, mesh = {Humans ; Middle Aged ; *Amyotrophic Lateral Sclerosis/therapy/complications/physiopathology ; *Respiratory Therapy/methods ; *Tracheostomy ; Treatment Outcome ; *Ventilator Weaning/methods ; Vital Capacity ; }, abstract = {We report a case of amyotrophic lateral sclerosis (ALS) in a patient in their 50s, presenting with spastic paraparesis and bulbar palsy, treated with lung volume recruitment therapy (LVRT). From early stage in the disease, vital capacity (VC), lung insufflation capacity (LIC) and ALS Functional Rating Scale-Revised scores were regularly measured, and LVRT was continuously performed at home. After 10 years, the patient had complete limb function loss and required nutritional management via gastrostomy and full assistance with daily activities. Despite this, the gap between VC and LIC remained approximately 2000 mL, and the patient was not ventilator-dependent during the day after tracheostomy. Chest CT showed improvement in lower lobe atelectasis due to LVRT. Typically, respiratory physiotherapy is challenging in patients with bulbar palsy or post-tracheostomy, but in this case, LVRT successfully maintained lung mobility. Early LVRT implementation may improve ALS patients' survival prognosis and warrants further exploration.}, } @article {pmid39828029, year = {2025}, author = {Fantini, J and Azzaz, F and Di Scala, C and Aulas, A and Chahinian, H and Yahi, N}, title = {Conformationally adaptive therapeutic peptides for diseases caused by intrinsically disordered proteins (IDPs). New paradigm for drug discovery: Target the target, not the arrow.}, journal = {Pharmacology & therapeutics}, volume = {267}, number = {}, pages = {108797}, doi = {10.1016/j.pharmthera.2025.108797}, pmid = {39828029}, issn = {1879-016X}, mesh = {*Intrinsically Disordered Proteins/chemistry/metabolism/antagonists & inhibitors ; Humans ; *Drug Discovery/methods ; *Peptides/therapeutic use/chemistry/pharmacology ; Protein Conformation ; Animals ; Drug Design ; }, abstract = {The traditional model of protein structure determined by the amino acid sequence is today seriously challenged by the fact that approximately half of the human proteome is made up of proteins that do not have a stable 3D structure, either partially or in totality. These proteins, called intrinsically disordered proteins (IDPs), are involved in numerous physiological functions and are associated with severe pathologies, e.g. Alzheimer, Parkinson, Creutzfeldt-Jakob, amyotrophic lateral sclerosis (ALS), and type 2 diabetes. Targeting these proteins is challenging for two reasons: i) we need to preserve their physiological functions, and ii) drug design by molecular docking is not possible due to the lack of reliable starting conditions. Faced with this challenge, the solutions proposed by artificial intelligence (AI) such as AlphaFold are clearly unsuitable. Instead, we suggest an innovative approach consisting of mimicking, in short synthetic peptides, the conformational flexibility of IDPs. These peptides, which we call adaptive peptides, are derived from the domains of IDPs that become structured after interacting with a ligand. Adaptive peptides are designed with the aim of selectively antagonizing the harmful effects of IDPs, without targeting them directly but through selected ligands, without affecting their physiological properties. This "target the target, not the arrow" strategy is promised to open a new route to drug discovery for currently undruggable proteins.}, } @article {pmid39828018, year = {2025}, author = {Sharma, D and Singh, V and Kumar, A and Singh, TG}, title = {Genistein: A promising ally in combating neurodegenerative disorders.}, journal = {European journal of pharmacology}, volume = {991}, number = {}, pages = {177273}, doi = {10.1016/j.ejphar.2025.177273}, pmid = {39828018}, issn = {1879-0712}, mesh = {*Genistein/therapeutic use/pharmacology ; Humans ; Animals ; *Neurodegenerative Diseases/drug therapy/metabolism ; *Neuroprotective Agents/therapeutic use/pharmacology ; }, abstract = {Neurodegenerative disorders arise when nerve cells in the brain or peripheral nervous system gradually lose functions and eventually die. Although certain therapies may alleviate some of the physical and mental symptoms associated with neurodegenerative disorders, hence slowing their progression, but no sure-shot treatment is currently available. It was shown that the rise in life expectancy and the number of elderly people in the community led to an increasing trend in the incidence and prevalence of neurodegenerative disease. Phytomolecules are demonstrating their effectiveness in combating, regression, and delaying various diseases. Genistein is one of soy isoflavone with antioxidant, anti-inflammatory, and estrogenic effects. Researchers demonstrated that Genistein treatment significantly reduced hyperglycemia, improved cognitive performance by modulating acetylcholinesterase activity and oxidative stress, and alleviated neuroinflammatory conditions in mice. This paper evaluates (in vivo and in vitro) various molecular targets of isoflavones and their ability to effectively counter several neurodegenerative disorders such as Parkinson's, Alzheimer's, and Huntington's diseases and amyotrophic lateral sclerosis. In this review, we aim to provide an overview of the role that genistein plays in delaying the development of neurodegenerative disorders.}, } @article {pmid39827940, year = {2025}, author = {Jinno, J and Abdelhamid, RF and Morita, J and Saga, R and Yamasaki, Y and Kadowaki, A and Ogawa, K and Kimura, Y and Ikenaka, K and Beck, G and Baba, K and Nagai, Y and Kasahara, E and Sekiyama, A and Hirayama, T and Hozumi, I and Hasegawa, T and Araki, T and Mochizuki, H and Nagano, S}, title = {TDP-43 transports ferritin heavy chain mRNA to regulate oxidative stress in neuronal axons.}, journal = {Neurochemistry international}, volume = {184}, number = {}, pages = {105934}, doi = {10.1016/j.neuint.2025.105934}, pmid = {39827940}, issn = {1872-9754}, mesh = {*Oxidative Stress/physiology ; *RNA, Messenger/metabolism/genetics ; *Apoferritins/metabolism/genetics ; *DNA-Binding Proteins/metabolism/genetics ; *Axons/metabolism ; Animals ; Humans ; *Neurons/metabolism ; *Ferritins/metabolism/genetics ; Iron/metabolism ; Oxidoreductases ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is characterized by the mislocalization and abnormal deposition of TAR DNA-binding protein 43 (TDP-43). This protein plays important roles in RNA metabolism and transport in motor neurons and glial cells. In addition, abnormal iron accumulation and oxidative stress are observed in the brain and spinal cord of patients with ALS exhibiting TDP-43 pathology and in animal models of ALS. We have previously demonstrated that TDP-43 downregulation significantly affects the expression of ferritin heavy chain (Fth1) mRNA in the axonal regions of neurons. Nevertheless, the mechanisms by which TDP-43 contributes to oxidative stress and iron accumulation in the central nervous system remain elusive. In this study, we aimed to investigate whether Fth1 mRNA is a target transported to the axon by TDP-43 using biophysical and biochemical analyses. Our results revealed Fth1 mRNA as a target mRNA transported to axons by TDP-43. Moreover, we demonstrated that TDP-43 regulates iron homeostasis and oxidative stress in neurons via Fth1 mRNA transport to the axons, possibly followed by a local translation of the ferritin heavy chain in the axons. This study suggests that TDP-43 plays an important role in preventing iron-mediated oxidative stress in neurons, with its loss contributing to ALS pathogenesis.}, } @article {pmid39827337, year = {2025}, author = {Mwale, PF and Hsieh, CT and Yen, TL and Jan, JS and Taliyan, R and Yang, CH and Yang, WB}, title = {Chitinase-3-like-1: a multifaceted player in neuroinflammation and degenerative pathologies with therapeutic implications.}, journal = {Molecular neurodegeneration}, volume = {20}, number = {1}, pages = {7}, pmid = {39827337}, issn = {1750-1326}, support = {NSTC 112-2320-B-038 -018 -MY3//National Science and Technology Council/ ; CGH-MR-A11315//Cathay General Hospital/ ; CGH-MR-A11314//Cathay General Hospital/ ; }, mesh = {Humans ; *Chitinase-3-Like Protein 1/metabolism ; *Neuroinflammatory Diseases/metabolism/pathology ; *Neurodegenerative Diseases/metabolism/pathology ; Animals ; Biomarkers/metabolism ; Inflammation/metabolism ; }, abstract = {Chitinase-3-like-1 (CHI3L1) is an evolutionarily conserved protein involved in key biological processes, including tissue remodeling, angiogenesis, and neuroinflammation. It has emerged as a significant player in various neurodegenerative diseases and brain disorders. Elevated CHI3L1 levels have been observed in neurological conditions such as traumatic brain injury (TBI), Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic lateral sclerosis (ALS), Creutzfeldt-Jakob disease (CJD), multiple sclerosis (MS), Neuromyelitis optica (NMO), HIV-associated dementia (HAD), Cerebral ischemic stroke (CIS), and brain tumors. This review explores the role of CHI3L1 in the pathogenesis of these disorders, with a focus on its contributions to neuroinflammation, immune cell infiltration, and neuronal degeneration. As a key regulator of neuroinflammation, CHI3L1 modulates microglia and astrocyte activity, driving the release of proinflammatory cytokines that exacerbate disease progression. In addition to its role in disease pathology, CHI3L1 has emerged as a promising biomarker for the diagnosis and monitoring of brain disorders. Elevated cerebrospinal fluid (CSF) levels of CHI3L1 have been linked to disease severity and cognitive decline, particularly in AD and MS, highlighting its potential for clinical diagnostics. Furthermore, therapeutic strategies targeting CHI3L1, such as small-molecule inhibitors and neutralizing antibodies, have shown promise in preclinical studies, demonstrating reduced neuroinflammation, amyloid plaque accumulation, and improved neuronal survival. Despite its therapeutic potential, challenges remain in developing selective and safe CHI3L1-targeted therapies, particularly in ensuring effective delivery across the blood-brain barrier and mitigating off-target effects. This review addresses the complexities of targeting CHI3L1, highlights its potential in precision medicine, and outlines future research directions aimed at unlocking its full therapeutic potential in treating neurodegenerative diseases and brain pathologies.}, } @article {pmid39825381, year = {2025}, author = {Gupta, R and Bhandari, M and Grover, A and Al-Shehari, T and Kadrie, M and Alfakih, T and Alsalman, H}, title = {Correction: Predictive modeling of ALS progression: an XGBoost approach using clinical features.}, journal = {BioData mining}, volume = {18}, number = {1}, pages = {5}, pmid = {39825381}, issn = {1756-0381}, } @article {pmid39824815, year = {2025}, author = {Leau, C and Wang, Y and Gervillié-Mouravieff, C and Boles, ST and Zhang, XH and Coudray, S and Boussard-Plédel, C and Tarascon, JM}, title = {Tracking solid electrolyte interphase dynamics using operando fibre-optic infra-red spectroscopy and multivariate curve regression.}, journal = {Nature communications}, volume = {16}, number = {1}, pages = {757}, pmid = {39824815}, issn = {2041-1723}, abstract = {As batteries drive the transition to electrified transportation and energy systems, ensuring their quality, reliability, lifetime, and safety is crucial. While the solid electrolyte interphase (SEI) is known to govern these performance characteristics, its dynamic nature makes understanding its nucleation, growth, and composition an ambitious, yet elusive aspiration. This work employs chalcogenide fibres embedded in negative electrode materials for operando Infra-red Fibre-optic Evanescent Wave Spectroscopy (IR-FEWS), combined with Multivariate Curve Resolution by Alternating Least Squares (MCR-ALS) algorithms for spectra analysis. By establishing molecular fingerprints that can be used to identify reaction products, IR-FEWS combined with MCR-ALS enables improved understanding of SEI evolution during cell formation with notable differences stemming from electrolyte or anode material. For example, despite operating at an elevated potential, lithium titanate's SEI has intrinsic instability, evidenced by continued carbonate formation. This approach leads the hunt for the SEI down a new path, giving empirical formulations theoretical roots.}, } @article {pmid39824736, year = {2025}, author = {Chow, G and Scher, M and Krisciunas, GP and Tracy, LF}, title = {Comprehensive Review of Multilingual Patient-Reported Outcome Measures for Dysphonia.}, journal = {Journal of voice : official journal of the Voice Foundation}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jvoice.2025.01.005}, pmid = {39824736}, issn = {1873-4588}, abstract = {INTRODUCTION: Patient-reported outcome measures (PROMs) represent an important part of a comprehensive voice assessment for clinical care and research. Access to multilingual PROMs enables inclusion of information from diverse patient populations. This review compares available translated and validated PROMs for adult dysphonia.

METHODS: A comprehensive review of Cochrane Library, PubMed, and OnBase was performed for PROMs evaluating adult dysphonia in all languages. References were additionally queried. PROM development process, available languages, and study group demographics were compared between PROMs available in at least one language other than English. Cultural validation for each PROM was assessed against Beaton et al's six-stage cross-cultural adaptation guidelines.

RESULTS: Of 21 PROMs assessing adult dysphonia, 13 (62%) were available in one or more language other than English, and nine (43%) were available in seven or more. Voice Handicap Index (VHI) and VHI-10 were the most widely available translated questionnaires (n = 29, n = 15) followed by Vocal Fatigue Index (VFI), Singing-VHI (S-VHI), and Voice-Related Quality of Life (V-RQOL) (n = 11). Identified questionnaires were available in English (n = 21), Persian (n = 9), Kannada (n = 8), and Turkish (n = 7) as the most common languages. Females averaged 60% (range 13%-81%) of dysphonic subject groups and 59% of non-dysphonic subject groups (range 20%-88%). Of the 113 articles that reported cultural validation techniques, 16 (14%) adequately fulfilled the cross-cultural adaptation guidelines used.

CONCLUSION: Multilingual PROMs for dysphonia are widely available, but linguistic representation varied. VHI, VFI, S-VHI, and V-RQOL are the most widely translated. The most represented languages were Persian, Kannada, and Turkish. Few studies adequately followed cross-cultural adaptation standards. Efforts to translate and validate questionnaires into different languages may allow more diverse assessment and comparison of larger populations with dysphonia. This review identifies translated PROMs for dysphonia and analyzes their level of cultural validation for future use.}, } @article {pmid39824655, year = {2025}, author = {Jia, M and Li, P and Yan, Y and Liu, X and Gao, L and Zhu, G and Chen, Z}, title = {Antimicrobial susceptibility and genomic characterization of Vibrio cholerae non-O1/non-O139 isolated from clinical and environmental samples in Jiaxing City, China.}, journal = {FEMS microbiology letters}, volume = {372}, number = {}, pages = {}, doi = {10.1093/femsle/fnaf009}, pmid = {39824655}, issn = {1574-6968}, support = {2024KY1697//Medical Science and Technology Project of Zhejiang Province/ ; 2023AY31028//Science and Technology Bureau of Jiaxing City/ ; }, mesh = {China ; Humans ; *Anti-Bacterial Agents/pharmacology ; Microbial Sensitivity Tests ; Multilocus Sequence Typing ; *Vibrio cholerae non-O1/genetics/drug effects/isolation & purification/pathogenicity/classification ; Drug Resistance, Bacterial/genetics ; Virulence/genetics ; Environmental Microbiology ; Virulence Factors/genetics ; Genome, Bacterial ; Genetic Variation ; }, abstract = {Non-O1/non-O139 (NOVC) strains inhabit aquatic environments and sporadically induce human illnesses. This study involved the virulence and antimicrobial genetic characterization of 176 NOVC strains, comprising 25 from clinical samples and 151 from environmental sources, collected between 2021 and 2023. The antimicrobial susceptibility of the examined NOVC population was predominantly high, exhibiting only poor susceptibility to colistin, with 89.2% resistance. The examination of virulence genes revealed that the majority of strains were positive for glucose metabolism (als gene) (169/176, 96.0%). Through multilocus sequence typing, the 176 NOVC strains were categorised into 121 sequence types, 79 of which were novel. NOVC strains demonstrate significant genetic variability and frequently engage in recombination. This work offers genetic characterization of the pathogenicity and antimicrobial resistance of a NOVC community. Our findings offer insights that may aid in the development of preventative and treatment methods for this pathogen.}, } @article {pmid39823474, year = {2025}, author = {Zhang, Y and He, L and Gundelach, J and Ge, A and Edlund, H and Norlin, S and Bram, RJ}, title = {Tail Anchored protein insertion mediated by CAML and TRC40 links to neuromuscular function in mice.}, journal = {PLoS genetics}, volume = {21}, number = {1}, pages = {e1011547}, pmid = {39823474}, issn = {1553-7404}, mesh = {Animals ; Mice ; *Amyotrophic Lateral Sclerosis/genetics/pathology/metabolism ; Endoplasmic Reticulum/metabolism/genetics ; Mice, Transgenic ; *Motor Neurons/metabolism/pathology ; Neuromuscular Junction/metabolism ; Protein Transport ; Spinal Cord/metabolism/pathology ; *Adaptor Proteins, Signal Transducing/genetics ; }, abstract = {Motor neuron diseases, such as amyotrophic lateral sclerosis (ALS) and progressive bulbar palsy, involve loss of muscle control resulting from death of motor neurons. Although the exact pathogenesis of these syndromes remains elusive, many are caused by genetically inherited mutations. Thus, it is valuable to identify additional genes that can impact motor neuron survival and function. In this report, we describe mice that express globally reduced levels of calcium-modulating cyclophilin ligand (CAML) protein. CAML is an essential component in the transmembrane domain recognition complex (TRC) pathway, responsible for inserting C-terminal tail anchored (TA) proteins into the endoplasmic reticulum membrane. The primary phenotype observed in these mice was rapid development of hind limb weakness and paralysis. Spinal cord sections revealed a loss of motor neuron cell bodies. Targeting CAML loss specifically to neurons using SLICK-H-Cre or synapsin-Cre transgenic mice yielded similar phenotypes, indicating that CAML plays a cell autonomous role in this process. We found that intracellular trafficking was perturbed in cells depleted of CAML, with aberrant release of procathepsin D and defective retention of CD222 within the trans-Golgi network, as well as reduced levels and mislocalization of syntaxin 5 (Stx5). Dysfunctional lysosomes and abnormal protein glycosylation were also revealed in CAML deficient cells, further indicating a defect in Golgi trafficking. In addition, we observed an identical phenotype in mice lacking ASNA1 in neurons, suggesting that CAML's role in sustaining muscle function is related to its involvement in the TRC pathway. Together, these findings implicate motor neuron survival as a key role for the TA protein insertion machinery in mice, which may shed light on the pathogenesis of neuromuscular disease in humans.}, } @article {pmid39823433, year = {2025}, author = {Tindale, A and Cretu, I and Gomez, N and Haynes, R and Meng, H and Mason, MJ and Francis, DP}, title = {Central venous pressure as a method of optimising atrio-ventricular delay after cardiac surgery.}, journal = {PloS one}, volume = {20}, number = {1}, pages = {e0310905}, pmid = {39823433}, issn = {1932-6203}, mesh = {Humans ; *Central Venous Pressure/physiology ; Male ; Female ; Aged ; *Cardiac Surgical Procedures ; Middle Aged ; *Heart Ventricles/physiopathology ; Pacemaker, Artificial ; *Heart Atria/physiopathology ; Aged, 80 and over ; }, abstract = {INTRODUCTION: Haemodynamic atrioventricular delay (AVD) optimisation has primarily focussed on signals that are not easy to acquire from a pacing system itself, such as invasive left ventricular catheterisation or arterial blood pressure (ABP). In this study, standard clinical central venous pressure (CVP) signals are tested as a potential alternative.

METHODS: Sixteen patients with a temporary pacemaker after cardiac surgery were studied. AV delay optimisation was performed by alternating between a reference AVD of 120ms and tested settings ranging from 40 to 280ms, with 8 replicates for each setting. Alongside (a) the raw data, three methods of correcting for respiration were tested: (b) limiting analysis to a respiratory cycle, (c) asymmetric least squares (ALS) and (d) discrete wavelet transform (DWT). The utility of a quality control step was tested.

RESULTS: CVP signals were a mirror image of the systolic ABP signals: The four R values were -0.674, -0.692, -0.631, -0.671 respectively (all p<0.001). With quality control, the mirror image was best for DWT (R = -0.76, p<0.001), with the CVP and ABP optima agreeing well (R = 0.78, p<0.001). The automated quality control signal correctly predicted the gap between the AVD optima calculated from ABP and CVP (R = 0.8, p<0.001).

CONCLUSIONS: Central venous pressure signals could be used to optimise AVD, because they have a reliable inverse relationship with ABP when pacemaker settings undergo protocolised testing. However, protocols need careful design to circumvent spontaneous biological variability.}, } @article {pmid39822067, year = {2025}, author = {Zhu, Y and Verkhratsky, A and Chen, H and Yi, C}, title = {Understanding glucose metabolism and insulin action at the blood-brain barrier: Implications for brain health and neurodegenerative diseases.}, journal = {Acta physiologica (Oxford, England)}, volume = {241}, number = {2}, pages = {e14283}, pmid = {39822067}, issn = {1748-1716}, support = {RCJC20231211090018040//Shenzhen Fundamental Research Program/ ; ZDSYS20220606100801003//Shenzhen Fundamental Research Program/ ; 2022B1515020012//Basic and Applied Basic Research Foundation of Guangdong Province/ ; 32170980//National Natural Science Foundation of China/ ; }, mesh = {*Blood-Brain Barrier/metabolism ; Humans ; *Neurodegenerative Diseases/metabolism ; Animals ; *Insulin/metabolism ; *Glucose/metabolism ; *Brain/metabolism ; }, abstract = {The blood-brain barrier (BBB) is a highly selective, semipermeable barrier critical for maintaining brain homeostasis. The BBB regulates the transport of essential nutrients, hormones, and signaling molecules between the bloodstream and the central nervous system (CNS), while simultaneously protecting the brain from potentially harmful substances and pathogens. This selective permeability ensures that the brain is nourished and shielded from toxins. An exception to this are brain regions, such as the hypothalamus and circumventricular organs, which are irrigated by fenestrated capillaries, allowing rapid and direct response to various blood components. We overview the metabolic functions of the BBB, with an emphasis on the impact of altered glucose metabolism and insulin signaling on BBB in the pathogenesis of neurodegenerative diseases. Notably, endothelial cells constituting the BBB exhibit distinct metabolic characteristics, primarily generating ATP through aerobic glycolysis. This occurs despite their direct exposure to the abundant oxygen in the bloodstream, which typically supports oxidative phosphorylation. The effects of insulin on astrocytes, which form the glial limitans component of the BBB, show a marked sexual dimorphism. BBB nutrient sensing in the hypothalamus, along with insulin signaling, regulates systemic metabolism. Insulin modifies BBB permeability by regulating the expression of tight junction proteins, angiogenesis, and vascular remodeling, as well as modulating blood flow in the brain. The disruptions in glucose and insulin signaling are particularly evident in neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease, where BBB breakdown accelerates cognitive decline. This review highlights the critical role of normal glucose metabolism and insulin signaling in maintaining BBB functionality and investigates how disruptions in these pathways contribute to the onset and progression of neurodegenerative diseases.}, } @article {pmid39821843, year = {2025}, author = {Zhang, J and Guo, R and Zhou, Z and Fu, Z and Akogo, HY and Li, Y and Zhang, X and Wang, N and Liu, Y and Li, H and Feng, B and Cui, H and Ma, J}, title = {Neural Stem/Progenitor Cell Therapy in Patients and Animals with Amyotrophic Lateral Sclerosis: A Systematic Review and Meta-analysis.}, journal = {Molecular neurobiology}, volume = {62}, number = {5}, pages = {6521-6536}, pmid = {39821843}, issn = {1559-1182}, support = {81801278//National Natural Science Foundation of China/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/therapy/physiopathology ; Animals ; Humans ; *Neural Stem Cells/transplantation/cytology ; *Stem Cell Transplantation/methods ; Disease Models, Animal ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative malady that causes progressive degeneration and loss of motor neuron function in the brain and spinal cord, eventually resulting in muscular atrophy, paralysis, and death. Neural stem/progenitor cell (NSPC) transplantation can improve bodily function in animals and delay disease progression in patients with ALS. This paper summarizes and analyzes the efficacy and safety of neural stem/progenitor cell (NSPC) transplantation as a treatment for ALS, aiming to improve function and delay disease progression in patients. We present a summary of the pathogenic mechanism and causative genes associated with ALS and describe the mechanism and efficacy of NSPC treatment for ALS. We comprehensively searched for relevant English-language articles published between January 1, 2000 and October 1, 2023, across the following five medical databases: PubMed, EMBASE, OVID, Web of Science, and the Cochrane Library. We examined experimental indices of physical function in animals and patients who underwent stem cell transplantation. All statistical analyses were performed via Review Manager 5.4. The study comprised a total of 16 investigations, including 5 clinical studies and 11 animal studies and involving 66 patients and 203 animals. The meta-analysis revealed that the administration of NSPCs appeared to yield positive outcomes in clinical patients, as assessed by the ALS functional rating scale and forced vital capacity. Furthermore, improvements following cell injection were observed in the rotarod test results, the Basso-Beattie-Bresnahan Locomotor Rating Scale score, weight, and survival time. Our meta-analysis, which was grounded in randomized controlled trials, revealed that the transplantation of neural stem/progenitor cells (NSPCs), has potential effects on ALS patients, enhancing the physical function of animals and mitigating degenerative effects in individuals. These underscored the promise of NSPC therapy as a viable treatment option. We report that the transplantation of neural stem/progenitor cells (NSPCs) is promising for enhancing bodily function and slowing the progression of ALS in affected patients. In this review, we summarize the treatment of ALS with NSPCs, evaluating both its efficacy and safety. Through database searches, we identified 16 studies involving 66 patients and 203 animals and analyzed the experimental indices of physical function following stem cell transplantation. The meta-analysis results indicated a positive impact of NSPCs on the clinical conditions of patients and the behavior of animals. A meta-analysis of randomized controlled trials further supported the conclusion that NSPC transplantation has a beneficial effect on improving physical function and mitigating degeneration in ALS patients.}, } @article {pmid39820998, year = {2025}, author = {Hamad, AA and Alkhawaldeh, IM and Nashwan, AJ and Meshref, M and Imam, Y}, title = {Tofersen for SOD1 amyotrophic lateral sclerosis: a systematic review and meta-analysis.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {46}, number = {5}, pages = {1977-1985}, pmid = {39820998}, issn = {1590-3478}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy/genetics ; *Superoxide Dismutase-1/genetics ; *Oligonucleotides/therapeutic use/pharmacology ; *Oligonucleotides, Antisense/therapeutic use/pharmacology ; }, abstract = {OBJECTIVE: Tofersen, an antisense oligonucleotide, has recently received FDA and EMA approval for treating amyotrophic lateral sclerosis (ALS) in adults with SOD1 gene mutations. This systematic review and meta-analysis synthesized evidence on tofersen's safety and efficacy in patients with SOD1-related ALS.

METHODS: A comprehensive search of three databases was conducted from inception through October 2024. Eligible studies included clinical trials, observational studies, and case studies. Meta-analyses were conducted using a random-effects model in RevMan.

RESULTS: Twelve studies involving 195 patients treated with tofersen met the inclusion criteria, comprising two randomized controlled trials (RCTs), five cohort studies, one case series, and four case reports. Tofersen demonstrated promising effects, notably reducing SOD1 levels in cerebrospinal fluid and neurofilament light chain (NfL) in plasma, a biomarker strongly correlated with ALS progression and survival. Meta-analysis of RCTs showed a significantly lower rate of decline in ALS Functional Rating Scale-Revised (ALSFRS-R) scores from baseline in the tofersen group compared to placebo (SMD = 0.44, 95% CI [0.05 to 0.83], P = 0.03) and a significant reduction in the decline of predicted Slow Vital Capacity (P = 0.005). In a pre-post meta-analysis of five studies, a significant decrease in ALS progression rate (ALSFRS-R decline rate) was observed (MD = -0.28, 95% CI [-0.40 to -0.15], P < 0.0001). Reported adverse events were consistent with ALS progression or procedural effects.

CONCLUSION: Current evidence suggests that tofersen effectively reduces SOD1 and NfL levels and slow disease progression in SOD1 ALS, showing promise as a targeted therapeutic option.}, } @article {pmid39820861, year = {2025}, author = {van Zundert, B and Montecino, M}, title = {Epigenetics in Neurodegenerative Diseases.}, journal = {Sub-cellular biochemistry}, volume = {108}, number = {}, pages = {73-109}, pmid = {39820861}, issn = {0306-0225}, mesh = {Humans ; *Epigenesis, Genetic ; Animals ; *Neurodegenerative Diseases/genetics/metabolism/pathology ; *DNA Methylation ; *Alzheimer Disease/genetics/pathology/metabolism ; *Amyotrophic Lateral Sclerosis/genetics/pathology/metabolism ; Frontotemporal Dementia/genetics/pathology/metabolism ; }, abstract = {Healthy brain functioning requires a continuous fine-tuning of gene expression, involving changes in the epigenetic landscape and 3D chromatin organization. Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), and frontotemporal dementia (FTD) are three multifactorial neurodegenerative diseases (NDDs) that are partially explained by genetics (gene mutations and genetic risk factors) and influenced by non-genetic factors (i.e., aging, lifestyle, and environmental conditions). Examining comprehensive studies of global and locus-specific (epi)genomic and transcriptomic alterations in human and mouse brain samples at the cell-type resolution has uncovered important phenomena associated with AD. First, DNA methylation and histone marks at promoters contribute to transcriptional dysregulation of genes that are directly implicated in AD pathogenesis (i.e., APP), neuroplasticity and cognition (i.e., PSD95), and microglial activation (i.e., TREM2). Second, the presence of AD genetic risk variants in cell-type-specific distal enhancers (i.e., BIN1 in microglia) alters transcription, presumably by disrupting associated enhancer-promoter interactions and chromatin looping. Third, epigenomic erosion is associated with widespread transcriptional disruption and cell identity loss. And fourth, aging, high cholesterol, air pollution, and pesticides have emerged as potential drivers of AD by inducing locus-specific and global epigenetic modifications that impact key AD-related pathways. Epigenetic studies in ALS/FTD also provide evidence that genetic and non-genetic factors alter gene expression profiles in neurons and astrocytes through aberrant epigenetic mechanisms. We additionally overview the recent development of potential new therapeutic strategies involving (epi)genetic editing and the use of small chromatin-modifying molecules (epidrugs).}, } @article {pmid39820267, year = {2025}, author = {Martinez-Thompson, JM and Mazurek, KA and Parra-Cantu, C and Naddaf, E and Gogineni, V and Botha, H and Jones, DT and Laughlin, RS and Barnard, L and Staff, NP}, title = {Artificial intelligence models using F-wave responses predict amyotrophic lateral sclerosis.}, journal = {Brain : a journal of neurology}, volume = {148}, number = {7}, pages = {2320-2330}, pmid = {39820267}, issn = {1460-2156}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/physiopathology ; Male ; Female ; Middle Aged ; Aged ; *Artificial Intelligence ; Retrospective Studies ; *Neural Conduction/physiology ; Adult ; }, abstract = {Nerve conduction F-wave studies contain crucial information about subclinical motor dysfunction that can be used to diagnose patients with amyotrophic lateral sclerosis (ALS). However, F-wave responses are highly variable in morphology, making waveform interpretation challenging. Artificial intelligence techniques can extract time-frequency features to provide new insights into ALS diagnosis and prognosis. A retrospective analysis was performed on F-wave responses from 46 802 patients. Discrete wavelet transforms were applied to time-series waveform responses after stimulating ulnar, median, fibular and tibial nerves. Wavelet coefficient statistics, onset age, sex and body mass index were features for training a Gradient Boosting Machine model on 40 095 patients (5329 diagnosed with motor neuron disease). Model performance was tested on responses from 689 ALS patients meeting Gold Coast criteria and 689 age- and sex-matched controls. An exploratory analysis examined model performance on cohorts of patients with inclusion body myositis, cervical radiculopathy, lumbar radiculopathy or peripheral neuropathy, which can mimic ALS symptoms. Factors affecting survival were estimated through Cox proportional hazards regression. The model trained using wavelet features on the full waveform had 90% recall, 87% precision and 88% accuracy. Similar model performance was measured using features from only the M-wave or F-wave. Classification probabilities for ALS patients were statistically different from the diagnoses mimicking ALS symptoms (P < 0.001, ANOVA, Tukey's post hoc test). Higher model classification probabilities of ALS, older age at onset, and family history of ALS alone or with frontotemporal dementia were factors decreasing survival. Longer diagnostic delay and upper limb onset site were factors increasing survival. Model scores two standard deviations below the mean had 4 months increased survival (two standard deviations below had 3 months decreased survival). Artificial intelligence techniques extracted important information from F-wave responses to estimate a patient's likelihood of ALS and their survival risks. Although the model can make predictions at a specific decision threshold as presented here, the true strength of such a model lies in its ability to provide probabilities about whether a patient is likely to have ALS in comparison to other mimicking diagnoses, such as inclusion body myositis, cervical or lumbar radiculopathy or peripheral neuropathy. These probabilities provide clinicians with additional information that they can use to make the final diagnosis with greater confidence and precision. Integrating such a model into the clinical workflow could help clinicians to diagnose ALS sooner and manage treatment based on estimated survival, which might improve outcomes and the quality of life of patients.}, } @article {pmid39819944, year = {2025}, author = {Kristensen, RK and Andersen, PT and Bilenberg, N and Milling, ED and Dalgaard Guldager, J}, title = {Mapping the landscape and evidence of cross-sectoral collaboration models targeting individuals referred for assessment of attention-deficit hyperactivity disorder or autism spectrum disorder: protocol for a scoping review.}, journal = {BMJ open}, volume = {15}, number = {1}, pages = {e088850}, pmid = {39819944}, issn = {2044-6055}, mesh = {Humans ; Scoping Review as Topic ; *Autism Spectrum Disorder/diagnosis/therapy ; *Attention Deficit Disorder with Hyperactivity/diagnosis/therapy ; Research Design ; *Referral and Consultation ; }, abstract = {INTRODUCTION: Neurodevelopmental disorders, notably attention-deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD), present substantial challenges in mental health. Individuals referred for assessment in a psychiatric unit experience complex needs. This implies that their needs necessitate coordination across multiple sectors. Cross-sectoral collaboration models have emerged as essential strategies for addressing the complexities of these disorders. However, evidence of their existence, implementation and success remains limited. This protocol aims to outline a scoping review where we will explore existing collaboration models, evaluate their implementation and gain an understanding of how cross-sectoral collaboration models can be developed to ultimately benefit individuals referred for assessment of ADHD or ASD.

METHODS AND ANALYSIS: This proposed scoping review will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidelines. A comprehensive search will be conducted across PubMed, CINAHL, Embase, PsycINFO and Google Scholar, as well as grey literature sources, between 1 December 2024 and 1 January 2025. Inclusion criteria will encompass studies focusing on cross-sectoral collaboration for individuals referred for assessment of ADHD or ASD, published in English, Danish, Norwegian or Swedish. The search will use a three-block search string, with iterative refinement guided by familiarity with the evidence base. Data extraction will involve study characteristics and implementation details, using the Consolidated Framework for Implementation Research in combination with Proctor et al's implementation outcomes framework. Results will be synthesised into descriptive tables, providing a comprehensive mapping of existing models and emphasising implementation feasibility.

ETHICS AND DISSEMINATION: Ethical approval is not required for this protocol since it involves the review of existing literature without the involvement of human participants or personal data. Findings will be disseminated at national and international conferences and will be integrated into future efforts to develop cross-sectoral collaboration models in Denmark.}, } @article {pmid39819841, year = {2025}, author = {Cintora-Sanz, AM and Horrillo-García, C and Quesada-Cubo, V and Pérez-Alonso, AM and Gutiérrez-Misis, A}, title = {Prevalence and Economic Impact of Acute Respiratory Failure in the Prehospital Emergency Medical Service of the Madrid Community: Retrospective Cohort Study.}, journal = {JMIR public health and surveillance}, volume = {11}, number = {}, pages = {e66179}, pmid = {39819841}, issn = {2369-2960}, mesh = {Humans ; Retrospective Studies ; *Emergency Medical Services/economics/statistics & numerical data ; Spain/epidemiology ; *Respiratory Insufficiency/epidemiology/economics/therapy ; Prevalence ; Male ; Female ; Aged ; COVID-19/epidemiology ; Middle Aged ; Pulmonary Disease, Chronic Obstructive/epidemiology ; Aged, 80 and over ; Acute Disease ; Health Care Costs/statistics & numerical data ; }, abstract = {BACKGROUND: Chronic obstructive pulmonary disease (COPD), congestive heart failure (CHF), and acute pulmonary edema (APE) are serious illnesses that often require acute care from prehospital emergency medical services (EMSs). These respiratory diseases that cause acute respiratory failure (ARF) are one of the main reasons for hospitalization and death, generating high health care costs. The prevalence of the main respiratory diseases treated in a prehospital environment in the prepandemic period and during the COVID-19 pandemic in Spain is unknown. The Madrid Community EMS is a public service that serves all types of populations and represents an epidemiological reference for supporting a population of 6.4 million inhabitants. The high volume of patients treated by Madrid's medical advanced life supports (ALSs) allows us to analyze this little-studied problem.

OBJECTIVES: Our goal was to lay the groundwork for comprehensive data collection and surveillance of respiratory failure, with an emphasis on the most prevalent diseases that cause it, an aspect that has been largely overlooked in previous initiatives. By achieving these objectives, we hope to inform efforts to address respiratory failure and establish a standardized methodology and framework that can facilitate expansion to a continuous community-wide registry in Madrid, driving advances in emergency care and care practices in these pathologies. The aim of this retrospective observational study was to determine the pathologies that have mainly caused respiratory failure in patients and required medicalized ALS and to evaluate the cost of care for these pathologies collected through this pilot registry.

METHODS: A multicenter descriptive study was carried out in the Madrid Community EMS. The anonymized medical records of patients treated with medical ALS, who received any of the following medical diagnoses, were extracted: ARF not related to chronic respiratory disease, ARF in chronic respiratory failure, exacerbations of COPD, APE, CHF, and bronchospasm (not from asthma or COPD). The prevalence of each pathology, its evolution from 2014 to 2020, and the economic impact of the Medical ALSs were calculated.

RESULTS: The study included 96,221 patients. The most common pathology was exacerbation of COPD, with a prevalence of 0.07% in 2014; it decreased to 0.03% in 2020. CHF followed at 0.06% in 2014 and 0.03% in 2020. APE had a prevalence of 0.01% in 2014, decreasing to 0.005% in 2020 with the pandemic. The greatest economic impact was on exacerbation of COPD in 2015, with an annual cost of €2,726,893 (which equals to US $2,864,628).

CONCLUSIONS: COPD exacerbations had the higher prevalence in the Madrid region among the respiratory diseases studied. With the COVID-19 pandemic, the prevalence and costs of almost all these diseases decreased, except for ARF not related to chronic disease. The cost of these pathologies over 5 years was €58,791,031 (US $61,832,879).}, } @article {pmid39819742, year = {2025}, author = {Xu, B and Lei, X and Yang, Y and Yu, J and Chen, J and Xu, Z and Ye, K and Zhang, J}, title = {Peripheral proteinopathy in neurodegenerative diseases.}, journal = {Translational neurodegeneration}, volume = {14}, number = {1}, pages = {2}, pmid = {39819742}, issn = {2047-9158}, support = {82020108012//National Natural Science Foundation of China/ ; 82371250//National Natural Science Foundation of China/ ; LY24H090006//Natural Science Foundation of Zhejiang Province/ ; LZ23H090002//Natural Science Foundation of Zhejiang Province/ ; 2024C03098//Key Research and Development Program of Zhejiang Province/ ; 2024SSYS0018//Key Research and Development Program of Zhejiang Province/ ; ZR2022QH177//Natural Science Foundation of Shandong Province/ ; }, mesh = {Humans ; *Neurodegenerative Diseases/metabolism/pathology ; Animals ; alpha-Synuclein/metabolism ; Amyloid beta-Peptides/metabolism ; tau Proteins/metabolism ; }, abstract = {Proteinopathies in neurology typically refer to pathological changes in proteins associated with neurological diseases, such as the aggregation of amyloid β and Tau in Alzheimer's disease, α-synuclein in Parkinson's disease and multiple system atrophy, and TAR DNA-binding protein 43 in amyotrophic lateral sclerosis and frontotemporal dementia. Interestingly, these proteins are also commonly found in peripheral tissues, raising important questions about their roles in neurological disorders. Multiple studies have shown that peripherally derived pathological proteins not only travel to the brain through various routes, aggravating brain pathology, but also contribute significantly to peripheral dysfunction, highlighting their crucial impact on neurological diseases. Investigating how these peripherally derived proteins influence the progression of neurological disorders could open new horizons for achieving early diagnosis and treatment. This review summarizes the distribution, transportation pathways, and pathogenic mechanisms of several neurodegenerative disease-related pathological proteins in the periphery, proposing that targeting these peripheral pathological proteins could be a promising strategy for preventing and managing neurological diseases.}, } @article {pmid39819257, year = {2025}, author = {Barton, M and Roman, A and Spencer, K and Cheng, L and Baylor, C}, title = {Examining the perspectives of augmentative and alternative communication (AAC) specialists on conducting AAC evaluations with people with amyotrophic lateral sclerosis via telehealth.}, journal = {Augmentative and alternative communication (Baltimore, Md. : 1985)}, volume = {41}, number = {2}, pages = {169-182}, doi = {10.1080/07434618.2024.2443669}, pmid = {39819257}, issn = {1477-3848}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/rehabilitation/complications ; *Communication Devices for People with Disabilities ; *Telemedicine ; *Speech-Language Pathology ; Male ; Female ; COVID-19 ; Middle Aged ; *Attitude of Health Personnel ; Adult ; *Communication Disorders/rehabilitation/diagnosis ; }, abstract = {The purpose of this study was to explore what speech-language pathologists (SLPs) who are AAC specialists see as advantages and disadvantages of providing AAC services via telehealth, how well tele-AAC assessments align with guidelines for in-person assessments, and how SLPs' perspectives of tele-AAC services changed post-COVID. Fifteen SLPs who are AAC specialists and experienced working with people with amyotrophic lateral sclerosis watched videos of speech generating device (SGD) assessments conducted via telehealth for eight people with amyotrophic lateral sclerosis. Using a checklist based on the AAC Clinical Assessment Project (AAC-CAP), the SLPs rated how comparable remote assessment was to in-person assessment, and described advantages and challenges. Across checklist elements, most participants rated AAC assessment via telemedicine as "same/comparable" to in-person assessment. The most common advantages of tele-AAC assessment were that tele-AAC was more functional, increased care partner availability, and increased clients' comfort at home. The most common challenges were technical difficulties and a limited comprehensive assessment due to the remote modality. Tele-AAC should be considered a viable assessment option as it may increase equitable access to care for more people with amyotrophic lateral sclerosis. Tools such as the AAC-CAP may help generalist SLPs increase their comfort and proficiency providing AAC services.}, } @article {pmid39818026, year = {2025}, author = {Choi, Y and Jung, HJ and Jung, HK and Jeong, E and Kim, S and Kim, JY and Lee, EJ and Lim, YM and Kim, H}, title = {In vivo imaging markers of glymphatic dysfunction in amyotrophic lateral sclerosis: Analysis of ALPS index and choroid plexus volume.}, journal = {Journal of the neurological sciences}, volume = {469}, number = {}, pages = {123393}, doi = {10.1016/j.jns.2025.123393}, pmid = {39818026}, issn = {1878-5883}, mesh = {*Glymphatic System/diagnostic imaging/pathology ; *Amyotrophic Lateral Sclerosis/diagnostic imaging/pathology ; *Choroid Plexus/diagnostic imaging ; Organ Size ; *Biomarkers/analysis ; Humans ; Male ; Female ; Middle Aged ; Aged ; Sensitivity and Specificity ; Diffusion Tensor Imaging ; Magnetic Resonance Imaging ; }, abstract = {BACKGROUND: The glymphatic system, essential for brain waste clearance, has been implicated in neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). Emerging imaging markers, such as the analysis along the perivascular space (ALPS) index and choroid plexus volume (CPV), may provide insights into glymphatic function, but their relevance to ALS remains unclear.

OBJECTIVE: To assess glymphatic dysfunction in ALS patients using the ALPS index and CPV.

METHODS: In this prospective single-center study, we analyzed 51 ALS patients and 51 age- and sex-matched healthy controls (HC). The ALPS index was calculated using diffusion tensor imaging, and 3D T1-weighted MRI was used for automated estimation of CPV and its fraction (CPV/total intracranial volume). Diagnostic performance was assessed using area under the receiver operating curve (AUC). Correlations between imaging markers and clinical parameters were also examined.

RESULTS: ALS patients had a significantly lower ALPS index (ALS: 1.45 ± 0.15; HC: 1.55 ± 0.16; p = 0.002) and higher CPV fraction (ALS: 0.12 ± 0.04 %; HC: 0.10 ± 0.02 %; p < 0.001). The ALPS index and CPV fraction had AUCs of 0.70 and 0.72, respectively. A significant inverse correlation was observed between the ALPS index and CPV fraction (r = -0.31, p = 0.002). Both markers correlated with aging but not with clinical disability or progression rate.

CONCLUSION: This study identifies glymphatic dysfunction in ALS, as evidenced by changes in the ALPS index and CPV. Larger studies are warranted to validate these findings and assess their potential as biomarkers for ALS.}, } @article {pmid39817908, year = {2025}, author = {Aikio, M and Odeh, HM and Wobst, HJ and Lee, BL and Chan, Ú and Mauna, JC and Mack, KL and Class, B and Ollerhead, TA and Ford, AF and Barbieri, EM and Cupo, RR and Drake, LE and Smalley, JL and Lin, YT and Lam, S and Thomas, R and Castello, N and Baral, A and Beyer, JN and Najar, MA and Dunlop, J and Gitler, AD and Javaherian, A and Kaye, JA and Burslem, GM and Brown, DG and Donnelly, CJ and Finkbeiner, S and Moss, SJ and Brandon, NJ and Shorter, J}, title = {Opposing roles of p38α-mediated phosphorylation and PRMT1-mediated arginine methylation in driving TDP-43 proteinopathy.}, journal = {Cell reports}, volume = {44}, number = {1}, pages = {115205}, pmid = {39817908}, issn = {2211-1247}, support = {K99 AG075242/AG/NIA NIH HHS/United States ; T32 AG000255/AG/NIA NIH HHS/United States ; R01 NS127187/NS/NINDS NIH HHS/United States ; R21 AG065854/AG/NIA NIH HHS/United States ; R35 GM142505/GM/NIGMS NIH HHS/United States ; F32 NS108598/NS/NINDS NIH HHS/United States ; R01 GM099836/GM/NIGMS NIH HHS/United States ; R01 LM013617/LM/NLM NIH HHS/United States ; F31 AG060672/AG/NIA NIH HHS/United States ; T32 GM008275/GM/NIGMS NIH HHS/United States ; F31 NS087676/NS/NINDS NIH HHS/United States ; }, mesh = {Humans ; Phosphorylation ; *Protein-Arginine N-Methyltransferases/metabolism ; Methylation ; *DNA-Binding Proteins/metabolism ; Amyotrophic Lateral Sclerosis/metabolism/pathology ; *Mitogen-Activated Protein Kinase 14/metabolism ; *Arginine/metabolism ; *TDP-43 Proteinopathies/metabolism/pathology ; Motor Neurons/metabolism/pathology ; *Repressor Proteins/metabolism ; HEK293 Cells ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder typically characterized by insoluble inclusions of hyperphosphorylated TDP-43. The mechanisms underlying toxic TDP-43 accumulation are not understood. Persistent activation of p38 mitogen-activated protein kinase (MAPK) is implicated in ALS. However, it is unclear how p38 MAPK affects TDP-43 proteinopathy. Here, we show that p38α MAPK inhibition reduces pathological TDP-43 phosphorylation, aggregation, cytoplasmic mislocalization, and neurotoxicity. Remarkably, p38α MAPK inhibition mitigates aberrant TDP-43 phenotypes in diverse ALS patient-derived motor neurons. p38α MAPK phosphorylates TDP-43 at pathological S409/S410 and S292, which reduces TDP-43 liquid-liquid phase separation (LLPS) but allows pathological TDP-43 aggregation. Moreover, we establish that PRMT1 methylates TDP-43 at R293. Importantly, S292 phosphorylation reduces R293 methylation, and R293 methylation reduces S409/S410 phosphorylation. Notably, R293 methylation permits TDP-43 LLPS and reduces pathological TDP-43 aggregation. Thus, strategies to reduce p38α-mediated TDP-43 phosphorylation and promote PRMT1-mediated R293 methylation could have therapeutic utility for ALS and related TDP-43 proteinopathies.}, } @article {pmid39817235, year = {2024}, author = {Cicardi, ME and Trotti, D}, title = {C9orf72 role in myeloid cells: new perspectives in the investigation of the neuro-immune crosstalk in amyotrophic lateral sclerosis and frontotemporal dementia.}, journal = {Annals of translational medicine}, volume = {12}, number = {6}, pages = {120}, pmid = {39817235}, issn = {2305-5839}, } @article {pmid39817215, year = {2025}, author = {Liu, SQ and Wang, D and Tang, CC}, title = {Association between age at diagnosis of diabetes and ocular disease: Insights from a recent article.}, journal = {World journal of diabetes}, volume = {16}, number = {1}, pages = {94846}, pmid = {39817215}, issn = {1948-9358}, abstract = {In this article, we discuss Ye et al's recent article on the association between age at diabetes diagnosis and subsequent risk of age-related ocular diseases. The study, which utilized United Kingdom Biobank data, highlighted a strong link between early diabetes onset and major eye conditions, such as cataracts, glaucoma, age-related macular degeneration, and vision loss, independent of glycemic control and disease duration. This finding challenges the previous belief that diabetic eye disease primarily correlates with hyperglycemia. As lifestyles evolve and the age of diabetes diagnosis decreases, understanding this relationship may reveal the complex pathogenesis underlying diabetes-related complications. This editorial summarizes potential mechanisms connecting the age of diabetes onset with four types of ocular diseases, emphasizing the significance of early diagnosis.}, } @article {pmid39817143, year = {2025}, author = {Chew, FY and Tsai, CH and Chang, KH and Chang, YK and Chou, RH and Liu, YJ}, title = {Exosomes as promising frontier approaches in future cancer therapy.}, journal = {World journal of gastrointestinal oncology}, volume = {17}, number = {1}, pages = {100713}, pmid = {39817143}, issn = {1948-5204}, abstract = {In this editorial, we will discuss the article by Tang et al published in the recent issue of the World Journal of Gastrointestinal Oncology. They explored an innovative approach to enhancing gemcitabine (GEM) delivery and efficacy using human bone marrow mesenchymal stem cells (HU-BMSCs)-derived exosomes. The manufacture of GEM-loaded HU-BMSCs-derived exosomes (Exo-GEM) has been optimized. The Tang et al's study demonstrated that Exo-GEM exhibits enhanced cytotoxicity and apoptosis-inducing effects compared to free GEM, highlighting the potential of exosome-based drug delivery systems as a more effective and targeted approach to chemotherapy in pancreatic cancer. Additional in vivo studies are required to confirm the safety and effectiveness of Exo-GEM before it can be considered for clinical use.}, } @article {pmid39817131, year = {2025}, author = {Lampridis, S}, title = {Unraveling the landscape of pediatric pancreatic tumors: Insights from Japan.}, journal = {World journal of gastrointestinal oncology}, volume = {17}, number = {1}, pages = {101477}, pmid = {39817131}, issn = {1948-5204}, abstract = {Pediatric pancreatic tumors, though rare, pose significant diagnostic and management challenges. The recent, 22-year nationwide survey on pediatric pancreatic tumors in Japan by Makita et al offers valuable insights into this uncommon entity, revealing striking geographical variations and questioning current treatment paradigms. This editorial commentary analyzes the study's key findings, including the predominance of solid pseudopapillary neoplasms and their younger age of onset, which contrast sharply with Western data. It explores the implications for clinical practice and research, emphasizing the need for population-specific approaches to diagnosis and treatment. The revealed limited institutional experience and surgical management patterns prompt a reevaluation of optimal care delivery for these complex cases, suggesting benefits of centralizing healthcare services. Furthermore, the commentary advocates for international collaborative studies to elucidate the genetic, environmental, and lifestyle factors influencing the development and progression of pediatric pancreatic tumors across diverse populations. It also outlines future directions, calling for advancements in precision medicine and innovative care delivery models to improve global patient outcomes. Unraveling Makita et al's findings within the broader landscape of pediatric oncology can stimulate further research and clinical advancements in managing pancreatic and other rare tumors in children.}, } @article {pmid39816195, year = {2025}, author = {Yildiz, O and Hunt, GP and Schroth, J and Dhillon, G and Spargo, TP and Al-Chalabi, A and Koks, S and Turner, MR and Shaw, PJ and Henson, SM and Iacoangeli, A and Malaspina, A}, title = {Lipid-mediated resolution of inflammation and survival in amyotrophic lateral sclerosis.}, journal = {Brain communications}, volume = {7}, number = {1}, pages = {fcae402}, pmid = {39816195}, issn = {2632-1297}, support = {/WT_/Wellcome Trust/United Kingdom ; }, abstract = {Neuroinflammation impacts on the progression of amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disorder. Specialized pro-resolving mediators trigger the resolution of inflammation. We investigate the specialized pro-resolving mediator blood profile and their receptors' expression in peripheral blood mononuclear cells in relation to survival in ALS. People living with ALS (pwALS) were stratified based on bulbar versus limb onset and on key progression metrics using a latent class model, to separate faster progressing from slower progressing ALS. Specialized pro-resolving mediator blood concentrations were measured at baseline and in one additional visit in 20 pwALS and 10 non-neurological controls (Cohort 1). Flow cytometry was used to study the GPR32 and GPR18 resolvin receptors' expression in peripheral blood mononuclear cells from 40 pwALS and 20 non-neurological controls (Cohort 2) at baseline and in two additional visits in 17 pwALS. Survival analysis was performed using Cox proportional hazards models, including known clinical predictors and GPR32 and GPR18 mononuclear cell expression. Differential expression and linear discriminant analyses showed that plasma resolvins were able to distinguish phenotypic variants of ALS from non-neurological controls. RvE3 was elevated in blood from pwALS, whilst RvD1, RvE3, RvT4 and RvD1n-3 DPA were upregulated in A-S and RvD2 in A-F. Compared to non-neurological controls, GPR32 was upregulated in monocytes expressing the active inflammation-suppressing CD11b[+] integrin from fast-progressing pwALS, including those with bulbar onset disease (P < 0.0024), whilst GPR32 and GPR18 were downregulated in most B and T cell subtypes. Only GPR18 was upregulated in naïve double positive Tregs, memory cytotoxic Tregs, senescent late memory B cells and late senescent CD8[+] T cells from pwALS compared to non-neurological controls (P < 0.0431). Higher GPR32 and GPR18 median expression in blood mononuclear cells was associated with longer survival, with GPR32 expression in classical monocytes (hazard ratio: 0.11, P = 0.003) and unswitched memory B cells (hazard ratio: 0.44, P = 0.008) showing the most significant association, along with known clinical predictors. Low levels of resolvins and downregulation of their membrane receptors in blood mononuclear cells are linked to a faster progression of ALS. Higher mononuclear cell expression of resolvin receptors is a predictor of longer survival. These findings suggest a lipid-mediated neuroprotective response that could be harnessed to develop novel therapeutic strategies and biomarkers for ALS.}, } @article {pmid39814005, year = {2025}, author = {Teive, HAG and Coutinho, L and Cardoso, FEC and Tsuji, S}, title = {Neurology pioneers in Japan.}, journal = {Arquivos de neuro-psiquiatria}, volume = {83}, number = {1}, pages = {1-3}, pmid = {39814005}, issn = {1678-4227}, mesh = {Japan ; *Neurology/history ; Bulbar Palsy, Progressive/history ; Amyotrophic Lateral Sclerosis/history ; Textbooks as Topic/history ; *Neurologists/history ; Humans ; Male ; History, 19th Century ; History, 20th Century ; }, abstract = {The pioneers of neurology in Japan were professors Hiroshi Kawahara and Kinnosuke Miura. Kawahara published the first description of progressive bulbar palsy and wrote the first neurology textbook in Japan. Miura, on the other hand, published studies about amyotrophic lateral sclerosis, in addition to participating in the founding of the Japanese Society of Neurology. The influence of European neurology, particularly French and German, in the figures of Professor Jean-Martin Charcot and Professor Erwin Bälz, was fundamental in the consolidation of neurology in Japan.}, } @article {pmid39813104, year = {2025}, author = {Corti, S and Hedlund, E}, title = {Intrinsic neuronal resilience as a tool for therapeutic discovery.}, journal = {Brain : a journal of neurology}, volume = {148}, number = {4}, pages = {1058-1061}, pmid = {39813104}, issn = {1460-2156}, support = {RF-2018-12366357//MoH/ ; //Ricerca Corrente 2024/ ; 2020-01049//The Swedish Research Council/ ; //Radala Foundation for ALS Research/ ; FO2023-0346//The Swedish Brain Foundation/ ; //Olov Thon's Foundation/ ; 233021//Åhlen Foundation/ ; //Ollie & Elof Ericssons Foundation to E.H./ ; }, abstract = {Corti and Hedlund argue that understanding the molecular underpinnings of neuronal resilience and vulnerability to neurodegenerative diseases such as ALS is key to identifying new therapeutic targets.}, } @article {pmid39812841, year = {2025}, author = {Didcote, L and Vitoratou, S and Al-Chalabi, A and Goldstein, LH}, title = {Predicting ALS informant distress from cognitive and behavioural change in people with ALS.}, journal = {Journal of neurology}, volume = {272}, number = {2}, pages = {144}, pmid = {39812841}, issn = {1432-1459}, support = {Goldstein/Oct17/892-792/MNDA_/Motor Neurone Disease Association/United Kingdom ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/psychology/complications ; Male ; Female ; Middle Aged ; Aged ; *Cognitive Dysfunction/psychology/etiology/diagnosis ; *Caregivers/psychology ; Adult ; *Psychological Distress ; *Stress, Psychological/psychology/diagnosis/etiology ; Depression/psychology ; COVID-19 ; }, abstract = {BACKGROUND: The cognitive and behavioural changes that occur in around 50% of people with amyotrophic lateral sclerosis (ALS) may significantly affect people around them, contributing to heightened burden, anxiety, and depression. Despite existing evidence linking behavioural impairment to caregiver distress, the role of cognitive impairment remains less clear, with mixed findings on its impact.

METHODS: This study assessed the influence of cognitive and behavioural impairments in people with ALS on the distress of their nominated informants. The data were collected face-to-face and remotely due to the COVID-19 pandemic. The cognitive and behavioural impairments were measured using established screening tools. Informants' distress was evaluated through composite measures of burden, anxiety, and depression. Regression analyses were employed to determine the predictive value of cognitive and behavioural impairment on informant distress.

RESULTS: A total of 98 ALS patients and 84 informants participated. Behavioural impairment predicted informant distress across various tools. In contrast, cognitive impairment was a less consistent predictor of informant distress across screening measures and did not significantly interact with behavioural impairment in predicting distress. Administration mode did not affect predictive relationships.

CONCLUSIONS: Behavioural impairment in ALS significantly predicts informant distress, with varying predictive power across different screening tools. Cognitive impairment also affects informant distress, but its impact is less substantial compared to behavioural factors. The interaction between cognitive and behavioural impairments did not significantly predict informant distress.}, } @article {pmid39812044, year = {2025}, author = {Liu, B and Chen, L and Chen, H and Pan, J and Yu, C}, title = {Bioinformatics Analysis Reveals Microrchidia Family Genes as the Prognostic and Therapeutic Markers for Colorectal Cancer.}, journal = {Endocrine, metabolic & immune disorders drug targets}, volume = {}, number = {}, pages = {}, doi = {10.2174/0118715303367767241231113110}, pmid = {39812044}, issn = {2212-3873}, abstract = {AIM: The aim of this study is to examine the role of the microrchidia (MORC) family, a group of chromatin remodeling proteins, as the therapeutic and prognostic markers for colorectal cancer (CRC).

BACKGROUND: MORC protein family genes are a highly conserved nucleoprotein superfamily whose members share a common domain but have distinct biological functions. Previous studies have analyzed the roles of MORCs as epigenetic regulators and chromatin remodulators; however, the involvement of MORCs in the development and pathogenesis of CRC was less examined.

OBJECTIVE: The current work examined the role of the MORCs as the therapeutic and prognostic markers for CRC.

METHODS: The expressions and prognostic significance of MORC family genes in CRC were explored. The role of these genes in tumor immunity was comprehensively analyzed in terms of their functions in immune cell infiltration, tumor microenvironment (TME), and their interaction with immune regulatory genes such as immunosuppressive genes, immune checkpoints and immunostimulatory genes. The relations between MORC family genes, tumor mutation burden (TMB), DNA, mismatch repair (MMR), RNA methylation, microsatellite instability (MSI), and drug sensitivity were investigated using the R statistical software. The expressions of MORC4 in 150 CRC tissues and 60 paracancer tissues were detected by immunohistochemical method. CRC cell proliferation, migration, and invasion were measured by cell counting kit-8 (CCK-8), scratch assay, and transwell cell invasion assay.

RESULTS: The expressions of MORC2 and MORC4 were significantly upregulated, whereas those of MORC1 and MORC3 were noticeably downregulated in CRC in comparison to their expressions in normal colorectal mucosal tissues. Patients with high-expressed MORC2 showed a more unfavorable prognosis than those with a low MORC2 level. Functional annotation analysis identified 100 MORC family genes with the most significant negative or positive correlations to diabetic cardiomyopathy, amyotrophic lateral sclerosis, oxidative phosphorylation, Huntington's disease, thermogenesis, Parkinson's disease, olfactory transduction, Alzheimer's disease, prion disease. MORC3 expression was positively correlated with Stromal score, Immune score and ESTIMATE score, while MORC2 expression was negatively related to the three scores in CRC, these correlations were not statistically significant. Additionally, the MORC family genes were significantly positively correlated with tumor-infiltrating immune cells such as T helper cells and exhibited close relations to some immunosuppressive genes such as CXCR4 and PVR, immunostimulatory genes such as TGFBR1, KDR, and CD160 as well as some immune checkpoint genes. It was found that the expressions of some members of MORC family genes were positively correlated with DNA methylation, MSI, TMB, MMRs, and drug sensitivity in CRC and that the mRNA and protein levels of MORC4 were remarkably upregulated in CRC tissues than in adjacent normal tissues (P<0.05). In the MORC4 knockdown group, DLD-1 cell proliferation was more inhibited than in the negative control (NC) and siRNA groups (P<0.05). Furthermore, the migratory capacity of DLD-1 cells and the number of cells crossing the basement membrane in the MORC4 knockdown group were reduced compared to the NC and siRNA groups (all P<0.05).

CONCLUSION: The expressions of MORC family genes were significantly different in CRC samples, which was related to the immune cell infiltration and prognosis of CRC. Thus, the MORC family genes were considered as markers for indicating the clinical immunotherapy and prognostic outcome of CRC.}, } @article {pmid39811452, year = {2024}, author = {Li, R and Bao, T and Li, B and Xia, P and Zhang, T and Zhang, H and Huang, F}, title = {Effectiveness and safety of traditional Chinese therapies intreating patients with amyotrophic lateral sclerosis: a protocol for systematic review and meta-analysis.}, journal = {Frontiers in neurology}, volume = {15}, number = {}, pages = {1519513}, pmid = {39811452}, issn = {1664-2295}, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a chronic, progressive disease that affects both upper and lower motor neurons. Some physicians have used traditional Chinese therapies (TCT) to treat ALS. However, there has been no systematic review or meta-analysis to evaluate the effectiveness and safety of TCT interventions. This review aims to analyze the effects of TCT interventions for patients with amyotrophic lateral sclerosis.

METHODS AND ANALYSIS: This study will include randomized, non-randomized, and quasi-experimental clinical trials, with participants being any age Amyotrophic Lateral Sclerosis (ALS) patients who have undergone TCT treatment. Two researchers will independently search databases including CENTRAL, PubMed, PEDro, EMBASE, CNKI, CBM, and SPORTDiscus, without restrictions on language or publication date. These researchers will independently screen titles and abstracts and extract data from the included studies. If deemed suitable for meta-analysis, data synthesis will be conducted using Review Manager V.5.3 software; any discrepancies will be resolved by a third researcher. The meta-analysis will compare the effects of TCT with placebo or other interventions. The main endpoint evaluated was the decrease in the overall score of the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R; scoring from 0 to 48, where higher scores denote greater functionality) over a period of 24 weeks. Additional endpoints included the reduction rates in isometric muscle power, levels of phosphorylated axonal neurofilament H subunits in plasma, and slow vital capacity measurements. Furthermore, the study monitored the duration until occurrence of death, tracheostomy, or the need for long-term ventilation, as well as the time until death, tracheostomy, long-term ventilation, or hospital admission.

ETHICS AND DISSEMINATION: Throughout the entire process of this systematic review, no personal information was used, hence ethical review is not required. The results of this meta-analysis will be disseminated through publication in peer-reviewed journals and/or conference presentations.}, } @article {pmid39810199, year = {2025}, author = {Eck, RJ and Valdmanis, PN and Liachko, NF and Kraemer, BC}, title = {Alternative 3' UTR polyadenylation is disrupted in the rNLS8 mouse model of ALS/FTLD.}, journal = {Molecular brain}, volume = {18}, number = {1}, pages = {1}, pmid = {39810199}, issn = {1756-6606}, support = {RF1 AG078374/AG/NIA NIH HHS/United States ; F99AG088436/NH/NIH HHS/United States ; R01 AG066729/AG/NIA NIH HHS/United States ; IK6 BX006467/BX/BLRD VA/United States ; R01 NS122766/NS/NINDS NIH HHS/United States ; F99 AG088436/AG/NIA NIH HHS/United States ; I01 BX005762/BX/BLRD VA/United States ; IK6BX006467//U.S. Department of Veterans Affairs/ ; R21AG082032/NH/NIH HHS/United States ; R01AG066729/NH/NIH HHS/United States ; RF1AG078374/NH/NIH HHS/United States ; }, mesh = {Animals ; *Amyotrophic Lateral Sclerosis/genetics ; *Polyadenylation/genetics ; Disease Models, Animal ; *3' Untranslated Regions/genetics ; *Frontotemporal Lobar Degeneration/genetics ; Mice ; Humans ; DNA-Binding Proteins/metabolism/genetics ; }, abstract = {Recent research has highlighted widespread dysregulation of alternative polyadenylation in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with TDP-43 pathology (FTLD-TDP). Here, we identify significant disruptions to 3` UTR polyadenylation in the ALS/FTLD-TDP mouse model rNLS8 that correlate with changes in gene expression and protein levels through the re-analysis of published RNA sequencing and proteomic data. A subset of these changes are shared with TDP-43 knock-down mice suggesting depletion of endogenous mouse TDP-43 is a contributor to polyadenylation dysfunction in rNLS8 mice. Some conservation exists between alternative polyadenylation in rNLS8 mice and human disease models including in disease relevant genes and biological pathways. Together, these findings support both TDP-43 loss and toxic gain-of-function phenotypes as contributors to the neurodegeneration in rNLS8 mice, nominating its continued utility as a preclinical model for investigating mechanisms of neurodegeneration in ALS/FTLD-TDP.}, } @article {pmid39810183, year = {2025}, author = {Harvey, C and Nowak, A and Zhang, S and Moll, T and Weimer, AK and Barcons, AM and Souza, CDS and Ferraiuolo, L and Kenna, K and Zaitlen, N and Caggiano, C and Shaw, PJ and Snyder, MP and Mill, J and Hannon, E and Cooper-Knock, J}, title = {Evaluation of a biomarker for amyotrophic lateral sclerosis derived from a hypomethylated DNA signature of human motor neurons.}, journal = {BMC medical genomics}, volume = {18}, number = {1}, pages = {10}, pmid = {39810183}, issn = {1755-8794}, support = {CEGS 5P50HG00773504//NIH (USA)/ ; 899-792/MNDA_/Motor Neurone Disease Association/United Kingdom ; NF-SI-0617-10077//National Institute for Health and Care Research/ ; /WT_/Wellcome Trust/United Kingdom ; IS-BRC-1215-20017//NIHR Sheffield Biomedical Research Centre/ ; 216596/Z/19/Z/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/pathology/cerebrospinal fluid ; *Motor Neurons/metabolism/pathology ; *Biomarkers/metabolism/cerebrospinal fluid/blood ; *DNA Methylation ; Cell-Free Nucleic Acids/cerebrospinal fluid/blood ; Induced Pluripotent Stem Cells/metabolism ; }, abstract = {Amyotrophic lateral sclerosis (ALS) lacks a specific biomarker, but is defined by relatively selective toxicity to motor neurons (MN). As others have highlighted, this offers an opportunity to develop a sensitive and specific biomarker based on detection of DNA released from dying MN within accessible biofluids. Here we have performed whole genome bisulfite sequencing (WGBS) of iPSC-derived MN from neurologically normal individuals. By comparing MN methylation with an atlas of tissue methylation we have derived a MN-specific signature of hypomethylated genomic regions, which accords with genes important for MN function. Through simulation we have optimised the selection of regions for biomarker detection in plasma and CSF cell-free DNA (cfDNA). However, we show that MN-derived DNA is not detectable via WGBS in plasma cfDNA. In support of our experimental finding, we show theoretically that the relative sparsity of lower MN sets a limit on the proportion of plasma cfDNA derived from MN which is below the threshold for detection via WGBS. Our findings are important for the ongoing development of ALS biomarkers. The MN-specific hypomethylated genomic regions we have derived could be usefully combined with more sensitive detection methods and perhaps with study of CSF instead of plasma. Indeed we demonstrate that neuronal-derived DNA is detectable in CSF. Our work is relevant for all diseases featuring death of rare cell-types.}, } @article {pmid39809929, year = {2025}, author = {Antico, O and Thompson, PW and Hertz, NT and Muqit, MMK and Parton, LE}, title = {Targeting mitophagy in neurodegenerative diseases.}, journal = {Nature reviews. Drug discovery}, volume = {24}, number = {4}, pages = {276-299}, pmid = {39809929}, issn = {1474-1784}, support = {/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Humans ; *Mitophagy/drug effects/physiology ; *Neurodegenerative Diseases/drug therapy/metabolism/genetics ; Animals ; Mitochondria/drug effects/metabolism ; Protein Kinases ; }, abstract = {Mitochondrial dysfunction is a hallmark of idiopathic neurodegenerative diseases, including Parkinson disease, amyotrophic lateral sclerosis, Alzheimer disease and Huntington disease. Familial forms of Parkinson disease and amyotrophic lateral sclerosis are often characterized by mutations in genes associated with mitophagy deficits. Therefore, enhancing the mitophagy pathway may represent a novel therapeutic approach to targeting an underlying pathogenic cause of neurodegenerative diseases, with the potential to deliver neuroprotection and disease modification, which is an important unmet need. Accumulating genetic, molecular and preclinical model-based evidence now supports targeting mitophagy in neurodegenerative diseases. Despite clinical development challenges, small-molecule-based approaches for selective mitophagy enhancement - namely, USP30 inhibitors and PINK1 activators - are entering phase I clinical trials for the first time.}, } @article {pmid39809899, year = {2025}, author = {Cui, Y and Arnold, FJ and Li, JS and Wu, J and Wang, D and Philippe, J and Colwin, MR and Michels, S and Chen, C and Sallam, T and Thompson, LM and La Spada, AR and Li, W}, title = {Multi-omic quantitative trait loci link tandem repeat size variation to gene regulation in human brain.}, journal = {Nature genetics}, volume = {57}, number = {2}, pages = {369-378}, pmid = {39809899}, issn = {1546-1718}, mesh = {Humans ; *Quantitative Trait Loci/genetics ; *Brain/metabolism ; *Gene Expression Regulation/genetics ; *Tandem Repeat Sequences/genetics ; Amyotrophic Lateral Sclerosis/genetics ; Phenotype ; Alzheimer Disease/genetics ; Genetic Variation ; Male ; C9orf72 Protein/genetics ; Female ; Multiomics ; }, abstract = {Tandem repeat (TR) size variation is implicated in ~50 neurological disorders, yet its impact on gene regulation in the human brain remains largely unknown. In the present study, we quantified the impact of TR size variation on brain gene regulation across distinct molecular phenotypes, based on 4,412 multi-omics samples from 1,597 donors, including 1,586 newly sequenced ones. We identified ~2.2 million TR molecular quantitative trait loci (TR-xQTLs), linking ~139,000 unique TRs to nearby molecular phenotypes, including many known disease-risk TRs, such as the G2C4 expansion in C9orf72 associated with amyotrophic lateral sclerosis. Fine-mapping revealed ~18,700 TRs as potential causal variants. Our in vitro experiments further confirmed the causal and independent regulatory effects of three TRs. Additional colocalization analysis indicated the potential causal role of TR variation in brain-related phenotypes, highlighted by a 3'-UTR TR in NUDT14 linked to cortical surface area and a TG repeat in PLEKHA1, associated with Alzheimer's disease.}, } @article {pmid39806943, year = {2024}, author = {Lee, K and Kim, SI and Shim, YM and Kim, EE and Yoo, S and Won, JK and Park, SH}, title = {Current Status and Future Perspective of Seoul National University Hospital-Dementia Brain Bank with Concordance of Clinical and Neuropathological Diagnosis.}, journal = {Experimental neurobiology}, volume = {33}, number = {6}, pages = {295-311}, pmid = {39806943}, issn = {1226-2560}, abstract = {This paper introduces the current status of Seoul National University Hospital Dementia Brain Bank (SNUH-DBB), focusing on the concordance rate between clinical diagnoses and postmortem neuropathological diagnoses. We detail SNUH-DBB operations, including protocols for specimen handling, induced pluripotent stem cells (iPSC) and cerebral organoids establishment from postmortem dural fibroblasts, and adult neural progenitor cell cultures. We assessed clinical-neuropathological diagnostic concordance rate. Between 2015 and September 2024, 162 brain specimens were collected via brain donation and autopsy. The median donor age was 73 years (1-94) with a male-to -female ratio of 2:1. The median postmortem interval was 9.5 hours (range: 2.5-65). Common neuropathological diagnoses included pure Lewy body disease (10.6%), Lewy body disease (LBD) with other brain diseases (10.6%), pure Alzheimer's disease-neuropathological change (ADNC) (6.0%), ADNC with other brain diseases (10.7%), vascular brain injury (15.2%), and primary age-related tauopathy (7.3%). APOE genotype distribution was following: ε3/ε3: 62.3%, ε2/ε3: 9.6%, ε2/ε4: 3.4%, ε3/ε4: 24.0%, and ε4/ε4: 0.7%. Concordance rates between pathological and clinical diagnoses were: ADNC/AD at 42.4%; LBD at 59.0%; PSP at 100%; ALS at 85.7%; Huntington's disease 100%. The varying concordance rates across different diseases emphasize the need for improved diagnostic criteria and biomarkers, particularly for AD and LBD. Tissues have been distributed to over 40 national studies. SNUH-DBB provides high-quality brain tissues and cell models for neuroscience research, operating under standardized procedures and international guidelines. It supports translational research in dementia and neurodegenerative diseases, potentially advancing diagnostic and therapeutic strategies.}, } @article {pmid39806490, year = {2025}, author = {Shen, Y and Zhang, X and Liu, S and Xin, L and Xuan, W and Zhuang, C and Chen, Y and Chen, B and Zheng, X and Wu, R and Lin, Y}, title = {CEST imaging combined with [1]H-MRS reveal the neuroprotective effects of riluzole by improving neurotransmitter imbalances in Alzheimer's disease mice.}, journal = {Alzheimer's research & therapy}, volume = {17}, number = {1}, pages = {20}, pmid = {39806490}, issn = {1758-9193}, support = {240428226498013//Shantou Science and Technology Project/ ; 213769/SNSF_/Swiss National Science Foundation/Switzerland ; 82020108016//National Natural Science Foundation of China/ ; 82071973//National Natural Science Foundation of China/ ; 2023A1515010326//Basic and Applied Basic Research Foundation of Guangdong Province/ ; 2022ZDZX2020//Key Research Platform and Project of Guangdong University/ ; }, mesh = {Animals ; *Alzheimer Disease/metabolism/drug therapy/diagnostic imaging ; *Riluzole/pharmacology/therapeutic use ; *Neuroprotective Agents/pharmacology/therapeutic use ; Mice ; *Glutamic Acid/metabolism ; *gamma-Aminobutyric Acid/metabolism ; Mice, Transgenic ; *Brain/drug effects/metabolism/diagnostic imaging ; Proton Magnetic Resonance Spectroscopy ; Disease Models, Animal ; Magnetic Resonance Imaging/methods ; Male ; *Neurotransmitter Agents/metabolism ; }, abstract = {BACKGROUND: The imbalance of glutamate (Glu) and gamma-aminobutyric acid (GABA) neurotransmitter system plays a crucial role in the pathogenesis of Alzheimer's disease (AD). Riluzole is a Glu modulator originally approved for amyotrophic lateral sclerosis that has shown potential neuroprotective effects in various neurodegenerative disorders. However, whether riluzole can improve Glu and GABA homeostasis in AD brain and its related mechanism of action remain unknown. This study utilized chemical exchange saturation transfer (CEST) imaging combined with proton magnetic resonance spectroscopy ([1]H-MRS) to monitor the dynamic changes of Glu and GABA in riluzole-treated AD mice, aiming to evaluate the efficacy and mechanism of riluzole in AD treatment.

METHODS: GluCEST, GABACEST and [1]H-MRS were used to longitudinally monitor Glu and GABA levels in 3xTg AD mice treated with riluzole (12.5 mg/kg/day) or vehicle for 20 weeks. Magnetic resonance measurements were performed at baseline, 6, 12, and 20 weeks post-treatment. Cognitive performance was assessed using the Morris Water Maze (MWM) at baseline, 10, and 20 weeks. At the study endpoint, immunohistochemistry, Nissl staining, and Western blot were used to evaluate the brain pathology, neuronal survival, and protein expression.

RESULTS: GluCEST, GABACEST and [1]H-MRS consistently revealed higher levels of Glu and GABA in the brain of riluzole-treated AD mice compared to untreated controls, which were associated with improvements in spatial learning and memory. The cognitive improvements significantly correlated with the increased GluCEST signals and Glu levels. Immunohistochemistry and Nissl staining demonstrated that riluzole treatment reduced amyloid-beta (Aβ) deposition, tau hyperphosphorylation, GFAP-positive astrocyte activation, and prevented neuronal loss. Moreover, riluzole upregulated the expression of excitatory amino acid transporter 2 (EAAT2), glutamic acid decarboxylase 65/67 (GAD65/67), and glutamine synthetase (GS), suggesting enhanced neurotransmitter metabolism.

CONCLUSIONS: CEST imaging combined with [1]H-MRS demonstrated the effectiveness of riluzole in modulating Glu- and GABA-related changes and improving cognitive function in 3xTg AD mice, potentially through regulating key proteins involved in neurotransmitter metabolism. These findings suggest riluzole as a therapeutic agent for Alzheimer's disease and highlight the utility of multimodal MR imaging in monitoring treatment response and exploring disease mechanisms.}, } @article {pmid39805247, year = {2025}, author = {Uzunçakmak-Uyanık, H and Yıldız, FG and Tan, E and Temuçin, ÇM}, title = {Thoracic paraspinal muscle concentric needle electrode jitter analysis in electrophysiological diagnosis of ALS.}, journal = {Journal of electromyography and kinesiology : official journal of the International Society of Electrophysiological Kinesiology}, volume = {81}, number = {}, pages = {102975}, doi = {10.1016/j.jelekin.2025.102975}, pmid = {39805247}, issn = {1873-5711}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology/diagnosis ; Male ; Female ; *Electromyography/instrumentation/methods ; Middle Aged ; *Paraspinal Muscles/physiopathology ; Needles ; Electrodes ; Reproducibility of Results ; Aged ; *Muscle Contraction ; Sensitivity and Specificity ; Adult ; }, abstract = {OBJECTIVES: Jitter analysis with concentric needle electrode of the thoracic 9 (T9) paraspinal muscle (PM), where the needle EMG examination at rest is difficult, was performed in both amyotrophic lateral sclerosis (ALS) patients and the controls.

METHODS: For the T9 PM, both upper limit for mean and individual mean consecutive difference (MCD) values and spike numbers were calculated according to jitter values of pairs from controls. In addition to the descriptive statistics, differences between two groups and T9 PM needle EMG and jitter analysis findings of patients were compared (p = 0.05).

RESULTS: Mean MCD median values of T9 PM were 62.8 and 26.2 µs in patient and controls respectively. Upper limit of mean and individual MCDs for the T9 PM were determined as 36.95 μs, 57.95 μs respectively. The differences between controls and patients in terms of all jitter analysis parametres (p < 0.001) and the comparison of patients' T9 PM needle EMG and jitter analysis findings grading were statistically significant (p = 0.029).

CONCLUSION: The T9 PM jitter analysis performed during routine EMG can be used to support the electrophysiological diagnosis of ALS in challenging cases and may contribute to minimizing the number of muscles examined. Furthermore, our study contributed to the T9 PM reference values for jitter analysis.}, } @article {pmid39804774, year = {2025}, author = {Agnihotri, D and Lee, CC and Lu, PC and He, RY and Huang, YA and Kuo, HC and Huang, JJ}, title = {C9ORF72 poly-PR induces TDP-43 nuclear condensation via NEAT1 and is modulated by HSP70 activity.}, journal = {Cell reports}, volume = {44}, number = {1}, pages = {115173}, doi = {10.1016/j.celrep.2024.115173}, pmid = {39804774}, issn = {2211-1247}, mesh = {Humans ; *HSP70 Heat-Shock Proteins/metabolism ; *C9orf72 Protein/metabolism/genetics ; *DNA-Binding Proteins/metabolism ; *Cell Nucleus/metabolism ; *RNA, Long Noncoding/metabolism/genetics ; *Peptides/metabolism ; Amyotrophic Lateral Sclerosis/metabolism/genetics/pathology ; }, abstract = {The toxicity of C9ORF72-encoded polyproline-arginine (poly-PR) dipeptide is associated with its ability to disrupt the liquid-liquid phase separation of intrinsically disordered proteins participating in the formation of membraneless organelles, such as the nucleolus and paraspeckles. Amyotrophic lateral sclerosis (ALS)-related TAR DNA-binding protein 43 (TDP-43) also undergoes phase separation to form nuclear condensates (NCs) in response to stress. However, whether poly-PR alters the nuclear condensation of TDP-43 in ALS remains unclear. In this study, we find that the poly-PR dipeptide enhances the formation of TDP-43 NCs with decreased fluidity. While the non-coding RNA, nuclear-enriched abundant transcript 1 (NEAT1), is essential for the formation of TDP-43 NCs, heat shock protein 70 (HSP70) chaperone maintains their fluidity. Under prolonged poly-PR stress, HSP70 delocalizes from TDP-43 NCs, leading to the oligomerization of TDP-43 within these condensates. This phenomenon is accompanied with TDP-43 mislocalization and increasing cytotoxicity. Our study demonstrates the role of NEAT1 and HSP70 in the aberrant phase transition of TDP-43 NCs under poly-PR stress.}, } @article {pmid39804470, year = {2025}, author = {Edgar, S and Zulhairy-Liong, NA and Ellis, M and Trivedi, S and Zhu, D and Odongo, JO and Goh, KJ and Capelle, DP and Shahrizaila, N and Kennerson, ML and Ahmad-Annuar, A}, title = {ATXN2 polyglutamine intermediate repeats length expansions in Malaysian patients with amyotrophic lateral sclerosis (ALS).}, journal = {Neurogenetics}, volume = {26}, number = {1}, pages = {19}, pmid = {39804470}, issn = {1364-6753}, support = {FRGS/1/2018/SKK08/UM/01/1//Malaysian Ministry of Education Fundamental Research Grant Scheme/ ; IF091-2022//ALS Association Seed Grant/ ; IF095-2023//ALS Association Seed Grant/ ; }, mesh = {Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; *Amyotrophic Lateral Sclerosis/genetics ; *Ataxin-2/genetics ; Genetic Predisposition to Disease ; Malaysia ; *Peptides/genetics ; *Trinucleotide Repeat Expansion/genetics ; Southeast Asian People/genetics ; }, abstract = {Intermediate CAG repeats from 29 to 33 in the ATXN2 gene contributes to the risk of amyotrophic lateral sclerosis (ALS) in European and Asian populations. In this study, 148 ALS patients of multiethnic descent: Chinese (56.1%), Malay (24.3%), Indian (12.8%), others (6.8%) and 100 neurologically normal controls were screened for the ATXN2 CAG repeat expansion. The most common repeat length in both the controls and patients was 22. No familial ALS patients were positive for the intermediate repeat sizes (29-33), while four sporadic patients (2.8%) were positive, with one harbouring a rare ATXN2 homozygous 32 repeat expansion, and a likely pathogenic variant in SPAST. All four patients had limb-onset ALS. Despite representing the smallest ethnic group in our patient cohort, three of the four patients with intermediate repeat sizes were of Indian ancestry. This study, which is the first in Malaysia and Southeast Asia, shows that ATXN2 intermediate risk expansions are relevant to ALS in these populations and will help to inform future genetic testing strategies in the clinic.}, } @article {pmid39803328, year = {2025}, author = {Niu, T and Wang, P and Zhou, X and Liu, T and Liu, Q and Li, R and Yang, H and Dong, H and Liu, Y}, title = {An overlap-weighted analysis on the association of constipation symptoms with disease progression and survival in amyotrophic lateral sclerosis: a nested case-control study.}, journal = {Therapeutic advances in neurological disorders}, volume = {18}, number = {}, pages = {17562864241309811}, pmid = {39803328}, issn = {1756-2856}, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a rapidly progressing and rare neurodegenerative disease. Therefore, evaluating the risk factors affecting the survival of patients with ALS is crucial. Constipation, a common but overlooked symptom of ALS, can be effectively managed. It is currently unknown whether constipation contributes to the progression and survival of ALS.

OBJECTIVES: This study aimed to investigate the association between constipation and ALS development and survival using a novel overlap-weighted (OW) method to enhance the robustness and reliability of results.

DESIGN: This prospective matching nested case-control (NCC) study was conducted within an ongoing ALS cohort at the Second Hospital of Hebei Medical University. Baseline data were collected from patients meeting the inclusion and exclusion criteria, with constipation as the exposure factor. A 9-month follow-up was conducted, with death as the endpoint event.

METHODS: We primarily used the OW method in NCC studies to examine the association between constipation and ALS development and survival. Weighted Cox proportional hazards model was used to assess risk factors associated with overall survival. Survival differences between the two groups were analyzed using Kaplan-Meier's plots and log-rank tests. Finally, the bioinformatic analysis explored common pathways between ALS and constipation.

RESULTS: Among the 190 patients included, the prevalence of constipation was 50%. Patients with ALS constipation exhibited faster disease progression (p < 0.001), with a positive correlation between constipation severity and progression rate (r = 0.356, p < 0.001). The constipation group had poorer survival before and after OW (log-rank test, p < 0.0001). In the Cox proportional hazards model of 114 patients, constipation was a risk factor for ALS both before (hazard ratio (HR) = 5.840, 95% confidence interval (CI) = 1.504-22.675, p = 0.011) and after (HR = 5.271, 95% CI = 1.241-22.379, p = 0.024) OW.

CONCLUSION: Constipation in individuals with ALS is associated with faster disease progression and reduced survival rates, potentially through the peroxisome proliferator-activated receptor pathway.}, } @article {pmid39802934, year = {2025}, author = {Ogonah, MGT and Botchway, S and Yu, R and Schofield, PW and Fazel, S}, title = {An umbrella review of health outcomes following traumatic brain injury.}, journal = {Nature. Mental health}, volume = {3}, number = {1}, pages = {83-91}, pmid = {39802934}, issn = {2731-6076}, abstract = {While numerous reviews have assessed the association between traumatic brain injury (TBI) and various mental and physical health outcomes, a comprehensive evaluation of the scope, validity, and quality of evidence is lacking. Here we present an umbrella review of a wide range of health outcomes following TBI and outline outcome risks across subpopulations. On 17 May 2023, we searched Embase, Medline, Global Health, PsycINFO, and Cochrane Database of Systematic Reviews for systematic reviews and meta-analyses. We compared risk ratios across different outcomes for risks compared with people without TBI and examined study quality, including heterogeneity, publication bias, and prediction intervals. The study was registered with PROSPERO (CRD42023432255). We identified 24 systematic reviews and meta-analyses covering 24 health outcomes in 31,397,958 participants. The current evidence base indicates an increased risk of multiple mental and physical health outcomes, including psychotic disorders, attention-deficit/hyperactivity disorder, suicide, and depression. Three outcomes-dementia, violence perpetration, and amyotrophic lateral sclerosis-had meta-analytical evidence of at least moderate quality, which suggest targets for more personalized assessment. Health-care services should review how to prevent adverse long-term outcomes in TBI.}, } @article {pmid39801873, year = {2025}, author = {Kumar, AJ and Sathiyaseelan, N and Vinodh, JB and Vignesh, A and Rathi, NK}, title = {Recent Advances in Managing Ankylosing Spondylitis with Andersson Lesion: A Clinical Overview and Case Report.}, journal = {Journal of orthopaedic case reports}, volume = {15}, number = {1}, pages = {21-25}, pmid = {39801873}, issn = {2250-0685}, abstract = {INTRODUCTION: Ankylosing spondylitis (AS) is a chronic inflammatory disorder that primarily affects the spine and sacroiliac joints, leading to pain, stiffness, and progressive thoracolumbar kyphotic deformity. A key complication in advanced AS is the development of Andersson lesions (AL), degenerative vertebral lesions resulting from the disease's progression. These lesions can cause significant mechanical pain, often mistaken for the chronic discomfort associated with AS. The exact cause of AL remains unclear, with hypotheses ranging from spinal stress fractures to delays in the ankylosing process. Understanding AL's pathophysiology is essential for timely diagnosis and effective management.

CASE REPORT: A 52-year-old male presented with a 20-year history of diffuse abdominal pain, later developing insidious lower back pain over the past 2 months. The pain was aggravated by walking and prolonged standing. Physical examination revealed tenderness in the D11 region of the spine, with limited chest expansion and positive findings on the modified Schober's test. Radiographic studies showed irregularities and erosions at the D11-D12 vertebral levels, and magnetic resonance imaging confirmed the presence of an AL associated with asymmetrical bilateral sacroiliitis. The patient tested positive for human leukocyte antigen-B27, supporting a diagnosis of AS with an AL. Medical management, including methotrexate, sulfasalazine, non-steroidal anti-inflammatory drugs, and corticosteroids, led to significant pain reduction and improved mobility. The patient's condition remained stable with continued treatment over a 2-year follow-up period.

CONCLUSION: AL s are chronic, often overlooked complications of AS that can lead to spinal instability and neurological deficits if untreated. Early recognition and management are critical to preventing progressive kyphotic deformities and associated complications. While conservative treatment remains the cornerstone for managing AL, surgical intervention may be required in cases of severe pain, deformity, or neurological involvement. Understanding AL's presentation and treatment options is vital for improving patient outcomes in AS.}, } @article {pmid39801792, year = {2024}, author = {Ansari, U and Wen, J and Syed, B and Nadora, D and Sedighi, R and Nadora, D and Chen, V and Lui, F}, title = {Analyzing the potential of neuronal pentraxin 2 as a biomarker in neurological disorders: A literature review.}, journal = {AIMS neuroscience}, volume = {11}, number = {4}, pages = {505-519}, pmid = {39801792}, issn = {2373-7972}, abstract = {Neuronal pentraxin 2 (NP2) plays a significant role in synaptic plasticity, neuronal survival, and excitatory synapse regulation. Emerging research suggests that NP2 is implicated in the pathogenesis of various neurological disorders, including neurodegenerative diseases, neuropsychiatric disorders, and neuropathies. This literature review extensively analyzes NP2's role in these conditions, thereby highlighting its contributions to synaptic dysfunction, neuroinflammation, and neurotoxic protein aggregation. In Alzheimer's and Parkinson's diseases, NP2 is linked to amyloid-beta aggregation and dopaminergic neuron degeneration, respectively. Additionally, altered NP2 expression is observed in schizophrenia and bipolar disorder, thus suggesting its involvement in synaptic dysfunction and neurotransmitter imbalance. In neuropathic pain and epilepsy, NP2 modulates the synaptic plasticity and inflammatory responses, with altered levels correlating with disease severity. Furthermore, NP2's involvement in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) emphasizes its broad impact on neuronal health. Understanding NP2's multifaceted roles may reveal novel therapeutic targets and improve the clinical outcomes for these neurological disorders. Though the precise role of NP2 remains uncertain, its clinical potential and initial findings justify further investigations into neuronal pentraxins and other related neuroproteins.}, } @article {pmid39801778, year = {2025}, author = {Ngo, HM and Khatib, T and Thai, MT and Kahveci, T}, title = {QOMIC: quantum optimization for motif identification.}, journal = {Bioinformatics advances}, volume = {5}, number = {1}, pages = {vbae208}, pmid = {39801778}, issn = {2635-0041}, abstract = {MOTIVATION: Network motif identification (MI) problem aims to find topological patterns in biological networks. Identifying disjoint motifs is a computationally challenging problem using classical computers. Quantum computers enable solving high complexity problems which do not scale using classical computers. In this article, we develop the first quantum solution, called QOMIC (Quantum Optimization for Motif IdentifiCation), to the MI problem. QOMIC transforms the MI problem using a integer model, which serves as the foundation to develop our quantum solution. We develop and implement the quantum circuit to find motif locations in the given network using this model.

RESULTS: Our experiments demonstrate that QOMIC outperforms the existing solutions developed for the classical computer, in term of motif counts. We also observe that QOMIC can efficiently find motifs in human regulatory networks associated with five neurodegenerative diseases: Alzheimer's, Parkinson's, Huntington's, Amyotrophic Lateral Sclerosis, and Motor Neurone Disease.

Our implementation can be found in https://github.com/ngominhhoang/Quantum-Motif-Identification.git.}, } @article {pmid39801516, year = {2024}, author = {Kamiyama, D and Nishida, Y and Kamiyama, R and Sego, A and Vining, G and Bui, K and Fitch, M and Do, H and Avraham, O and Chihara, T}, title = {The VAPB Axis Precisely Coordinates the Timing of Motoneuron Dendritogenesis in Neural Map Development.}, journal = {Research square}, volume = {}, number = {}, pages = {}, pmid = {39801516}, issn = {2693-5015}, support = {P40 OD018537/OD/NIH HHS/United States ; R01 NS107558/NS/NINDS NIH HHS/United States ; }, abstract = {In Drosophila motoneurons, spatiotemporal dendritic patterns are established in the ventral nerve cord. While many guidance cues have been identified, the mechanisms of temporal regulation remain unknown. Previously, we identified the actin modulator Cdc42 GTPase as a key factor in this process. In this report, we further identify the upstream factors that activate Cdc42. Using single-cell genetics, FRET-based imaging, and biochemical techniques, we demonstrate that the guanine nucleotide exchange factor Vav is anchored to the plasma membrane via the Eph receptor tyrosine kinase, enabling Cdc42 activation. VAMP-associated protein 33 (Vap33), an Eph ligand supplied non-cell-autonomously, may induce Eph autophosphorylation, initiating downstream signaling. Traditionally known as an ER-resident protein, Vap33 is secreted extracellularly at the onset of Cdc42 activation, acting as a temporal cue. In humans, VAPB-the ortholog of Vap33-is similarly secreted in the spinal cord, and its dysregulation leads to amyotrophic lateral sclerosis type 8 (ALS8) and spinal muscular atrophy (SMA). Our findings provide a framework linking VAPB signaling to motor circuitry formation in both health and disease.}, } @article {pmid39801319, year = {2025}, author = {Oliveira Santos, M and Domingues, S and Simão, S and Gromicho, M and Alves, I and de Carvalho, M}, title = {The Role of Gastrostomy and Noninvasive Ventilation in Primary Lateral Sclerosis.}, journal = {Muscle & nerve}, volume = {71}, number = {3}, pages = {450-456}, doi = {10.1002/mus.28346}, pmid = {39801319}, issn = {1097-4598}, mesh = {Humans ; *Gastrostomy/methods ; *Noninvasive Ventilation/methods ; Male ; Female ; Middle Aged ; Retrospective Studies ; Aged ; *Respiratory Insufficiency/therapy/etiology ; *Deglutition Disorders/etiology/therapy ; Adult ; *Motor Neuron Disease/therapy/complications ; }, abstract = {INTRODUCTION/AIMS: Literature on the role of gastrostomy and noninvasive ventilation (NIV) in primary lateral sclerosis (PLS) is limited. We aim to investigate whether PLS patients develop dysphagia requiring feeding tubes or respiratory failure necessitating NIV.

METHODS: We conducted a retrospective study of PLS patients with a definite diagnosis followed at our center (1994-2024). Patients with marked dysphagia (score < 3 on Question 3 of the ALSFRS-R) received a recommendation for gastrostomy and were divided into two groups: G1/G2 (accepted/declined gastrostomy). We investigated NIV indications due to respiratory failure and compared these patients (G3) to those without respiratory impairment (G4). Demographic, clinical, and neurophysiological data were collected and compared.

RESULTS: Forty-eight patients had a definite diagnosis of PLS. Gastrostomy was recommended to 18 (37.5%), yet only 7 patients (38.9%-G1) consented. The median time to gastrostomy was 77 months. Total survival and survival post-gastrostomy recommendation were not different between G1 and G2. Six PLS patients (12.5%-G3) developed respiratory failure and initiated NIV (median of 63 months). At 63 months, G3 had significantly lower median forced vital capacity (65% vs. 99%; p < 0.001) and phrenic nerve amplitude (0.43 vs. 0.75 mV; p = 0.039), but a greater ALSFRS-R slope (0.34 vs. 0.14; p = 0.046) and shorter survival (35 vs. 94.9 months; p = 0.009) compared to G4.

DISCUSSION: Dysphagia requiring gastrostomy was common in our PLS cohort, but survival after gastrostomy recommendation did not differ between groups. Patients who developed respiratory impairment may represent a distinct group with faster disease progression and shorter survival. Our findings may contribute to a deeper understanding and improved management of PLS.}, } @article {pmid39799559, year = {2025}, author = {Üremiş, N and Üremiş, MM}, title = {Oxidative/Nitrosative Stress, Apoptosis, and Redox Signaling: Key Players in Neurodegenerative Diseases.}, journal = {Journal of biochemical and molecular toxicology}, volume = {39}, number = {1}, pages = {e70133}, pmid = {39799559}, issn = {1099-0461}, support = {//This research was supported by the Türkiye Bilimsel ve Teknolojik Araştırma Kurumu (grant number: TUB1)./ ; }, mesh = {Humans ; *Apoptosis ; *Oxidative Stress ; *Neurodegenerative Diseases/metabolism/pathology ; *Nitrosative Stress ; Animals ; *Signal Transduction ; Oxidation-Reduction ; Reactive Nitrogen Species/metabolism ; Reactive Oxygen Species/metabolism ; }, abstract = {Neurodegenerative diseases are significant health concerns that have a profound impact on the quality and duration of life for millions of individuals. These diseases are characterized by pathological changes in various brain regions, specific genetic mutations associated with the disease, deposits of abnormal proteins, and the degeneration of neurological cells. As neurodegenerative disorders vary in their epidemiological characteristics and vulnerability of neurons, treatment of these diseases is usually aimed at slowing disease progression. The heterogeneity of genetic and environmental factors involved in the process of neurodegeneration makes current treatment methods inadequate. However, the existence of common molecular mechanisms in the pathogenesis of these diseases may allow the development of new targeted therapeutic strategies. Oxidative and nitrosative stress damages membrane components by accumulating ROS and RNS and disrupting redox balance. This process results in the induction of apoptosis, which is important in the pathogenesis of neurodegenerative diseases through oxidative stress. Studies conducted using postmortem human samples, animal models, and cell cultures have demonstrated that oxidative stress, nitrosative stress, and apoptosis are crucial factors in the development of diseases such as Alzheimer's, Parkinson's, Multiple Sclerosis, amyotrophic lateral sclerosis, and Huntington's disease. The excessive production of reactive oxygen and nitrogen species, elevated levels of free radicals, heightened mitochondrial stress, disturbances in energy metabolism, and the oxidation and nitrosylation of cellular macromolecules are recognized as triggers for neuronal cell death. Challenges in managing and treating neurodegenerative diseases require a better understanding of this field at the molecular level. Therefore, this review elaborates on the molecular mechanisms by which oxidative and nitrosative stress are involved in neuronal apoptosis.}, } @article {pmid39799393, year = {2025}, author = {Valenzuela, V and Becerra, D and Astorga, JI and Fuentealba, M and Diaz, G and Bargsted, L and Chacón, C and Martinez, A and Gozalvo, R and Jackson, K and Morales, V and Heras, ML and Tamburini, G and Petrucelli, L and Sardi, SP and Plate, L and Hetz, C}, title = {Artificial enforcement of the unfolded protein response reduces disease features in multiple preclinical models of ALS/FTD.}, journal = {Molecular therapy : the journal of the American Society of Gene Therapy}, volume = {33}, number = {3}, pages = {1226-1245}, pmid = {39799393}, issn = {1525-0024}, mesh = {Animals ; *Unfolded Protein Response/genetics ; *Amyotrophic Lateral Sclerosis/metabolism/genetics/therapy/pathology ; Disease Models, Animal ; Mice ; *Frontotemporal Dementia/metabolism/genetics/therapy/pathology ; *X-Box Binding Protein 1/genetics/metabolism ; Humans ; Dependovirus/genetics ; Endoplasmic Reticulum Stress/genetics ; Mice, Transgenic ; Genetic Vectors/administration & dosage/genetics ; Superoxide Dismutase-1/genetics ; Genetic Therapy ; }, abstract = {Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are part of a spectrum of diseases that share several causative genes, resulting in a combinatory of motor and cognitive symptoms and abnormal protein aggregation. Multiple unbiased studies have revealed that proteostasis impairment at the level of the endoplasmic reticulum (ER) is a transversal pathogenic feature of ALS/FTD. The transcription factor XBP1s is a master regulator of the unfolded protein response (UPR), the main adaptive pathway to cope with ER stress. Here, we provide evidence of suboptimal activation of the UPR in ALS/FTD models under experimental ER stress. To artificially engage the UPR, we intracerebroventricularly administrated adeno-associated viruses (AAVs) to express the active form of XBP1 (XBP1s) in the nervous system of ALS/FTD models. XBP1s expression improved motor performance and extended lifespan of mutant SOD1 mice, associated with reduced protein aggregation. AAV-XBP1s administration also attenuated disease progression in models of TDP-43 and C9orf72 pathogenesis. Proteomic profiling of spinal cord tissue revealed that XBP1s overexpression improved proteostasis and modulated the expression of a cluster of synaptic and cell morphology proteins. Our results suggest that strategies to improve ER proteostasis may serve as a pan-therapeutic strategy to treat ALS/FTD.}, } @article {pmid39799324, year = {2025}, author = {Freiha, J and Grand, E and Marshall, B and Arunchalam, R and Pinto, A and Osman, C}, title = {Amyotrophic lateral sclerosis in a patient with chronic lymphocytic leukaemia and drug related sarcoid-like reaction.}, journal = {BMC neurology}, volume = {25}, number = {1}, pages = {16}, pmid = {39799324}, issn = {1471-2377}, mesh = {Humans ; Male ; *Amyotrophic Lateral Sclerosis/diagnosis/complications/chemically induced ; Middle Aged ; *Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy/complications ; *Sarcoidosis/chemically induced/diagnosis/complications ; Rituximab/adverse effects ; Sulfonamides/adverse effects ; }, abstract = {Sarcoid-like reaction is an immunological reaction that can affect lymph nodes and organs but does not meet the diagnostic criteria for systemic sarcoidosis. Anti-CD20 auto-antibodies have been reported to be responsible for such reactions. There are several reported associations between Chronic lymphocytic leukaemia (CLL), Amyotrophic lateral sclerosis (ALS) and Sarcoid-like reactions (SLR). We report a case of ALS developing in a patient with treated CLL and drug related SLR one day after exposure to Venetoclax and Rituximab. A 60-year-old male presented with lower limb rash, left leg weakness followed by bulbar symptoms which progressed over 12-months. Workup demonstrated a Cerebrospinal fluid (CSF) pleocytosis and inguinal lymphadenopathy. Skin and inguinal lymph node biopsies showed non-necrotising granulomata. Electromyography met diagnostic criteria for ALS. He was treated for presumed neurosarcoidosis mimicking ALS. Despite prednisolone and infliximab treatment, the motor symptoms rapidly progressed; Hence, we made a clinical diagnosis of ALS. We discuss the diagnostic and treatment challenges of this case.}, } @article {pmid39799044, year = {2025}, author = {Bracca, V and Premi, E and Cotelli, MS and Micheli, A and Altomare, D and Cantoni, V and Gasparotti, R and Borroni, B}, title = {Loss of Insight in Syndromes Associated with Frontotemporal Lobar Degeneration: Clinical and Imaging Features.}, journal = {The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry}, volume = {33}, number = {4}, pages = {450-462}, doi = {10.1016/j.jagp.2024.12.005}, pmid = {39799044}, issn = {1545-7214}, mesh = {Humans ; Male ; Female ; Aged ; *Frontotemporal Lobar Degeneration/diagnostic imaging/pathology/psychology/physiopathology/complications ; Magnetic Resonance Imaging ; Longitudinal Studies ; Retrospective Studies ; Middle Aged ; *Aphasia, Primary Progressive/diagnostic imaging/physiopathology/pathology ; *Brain/diagnostic imaging/pathology ; *Amyotrophic Lateral Sclerosis/diagnostic imaging/physiopathology ; Atrophy ; }, abstract = {OBJECTIVES: The present study aims to assess the prevalence, associated clinical symptoms, longitudinal changes, and imaging correlates of Loss of Insight (LOI), which is still unexplored in syndromes associated with Frontotemporal Lobar Degeneration (FTLD).

DESIGN: Retrospective longitudinal cohort study, from Oct 2009 to Feb 2023.

SETTING: Tertiary Frontotemporal Dementia research clinic.

PARTICIPANTS: A sample of 712 FTLD patients, 331 of whom had follow-up evaluation.

MEASUREMENTS: LOI was assessed by interview with the primary caregiver. Univariate and multiple logistic regression and linear mixed models were used to estimate predictors and longitudinal changes over time associated with LOI. Voxel-based morphometry and structural covariance analyses of brain structural MRI images were implemented in Statistical Parametric Mapping.

RESULTS: LOI was reported in 45% of patients (321/712, 95%CI = 41-49), with progressively increased prevalence from prodromal to severe dementia stages. LOI was more prevalent in the behavioural variant FTD, in the semantic variant of Primary Progressive Aphasia (svPPA) and FTD with Amyotrophic Lateral Sclerosis than in other phenotypes (all p-values<0.001). LOI severity increased over time only in patients with svPPA (β = +0.59, p <0.001) and clustered with other behavioral symptoms (all p-values <0.05). Finally, LOI was significantly associated with greater atrophy in the right medial orbital gyrus (p <0.001 uncorrected). Structural covariance analysis demonstrated loss of negative correlation between right medial orbital gyrus and regions belonging to the Default Mode Network (DMN), such as the left precuneus and the left angular gyrus (p ≤0.05 family-wise error-corrected) in FTLD patients with LOI.

CONCLUSIONS: A better comprehension of LOI mechanisms could lead to more effective interventions and healthcare policies.}, } @article {pmid39798947, year = {2025}, author = {Sorice, V and Ekumah, ND}, title = {Exploring the psychosocial dimensions and impacts of infertility in Africa: a commentary on Roomaney et al's scoping review of current evidence.}, journal = {Evidence-based nursing}, volume = {}, number = {}, pages = {}, doi = {10.1136/ebnurs-2024-104222}, pmid = {39798947}, issn = {1468-9618}, } @article {pmid39798853, year = {2025}, author = {Guan, D and Liang, C and Zheng, D and Liu, S and Luo, J and Cai, Z and Zhang, H and Chen, J}, title = {The role of mitochondrial remodeling in neurodegenerative diseases.}, journal = {Neurochemistry international}, volume = {183}, number = {}, pages = {105927}, doi = {10.1016/j.neuint.2024.105927}, pmid = {39798853}, issn = {1872-9754}, mesh = {Humans ; *Neurodegenerative Diseases/metabolism/pathology ; *Mitochondria/metabolism/pathology ; Animals ; Energy Metabolism/physiology ; *Mitochondrial Dynamics/physiology ; }, abstract = {Neurodegenerative diseases are a group of diseases that pose a serious threat to human health, such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD) and Amyotrophic Lateral Sclerosis (ALS). In recent years, it has been found that mitochondrial remodeling plays an important role in the onset and progression of neurodegenerative diseases. Mitochondrial remodeling refers to the dynamic regulatory process of mitochondrial morphology, number and function, which can affect neuronal cell function and survival by regulating mechanisms such as mitochondrial fusion, division, clearance and biosynthesis. Mitochondrial dysfunction is an important intrinsic cause of the pathogenesis of neurodegenerative diseases. Mitochondrial remodeling abnormalities are involved in energy metabolism in neurodegenerative diseases. Pathological changes in mitochondrial function and morphology, as well as interactions with other organelles, can affect the energy metabolism of dopaminergic neurons and participate in the development of neurodegenerative diseases. Since the number of patients with PD and AD has been increasing year by year in recent years, it is extremely important to take effective interventions to significantly reduce the number of morbidities and to improve people's quality of life. More and more researchers have suggested that mitochondrial remodeling and related dynamics may positively affect neurodegenerative diseases in terms of neuronal and self-adaptation to the surrounding environment. Mitochondrial remodeling mainly involves its own fission and fusion, energy metabolism, changes in channels, mitophagy, and interactions with other cellular organelles. This review will provide a systematic summary of the role of mitochondrial remodeling in neurodegenerative diseases, with the aim of providing new ideas and strategies for further research on the treatment of neurodegenerative diseases.}, } @article {pmid39798254, year = {2025}, author = {Cao, S and Fu, X and Li, W and Wang, P and Li, C and Shang, H}, title = {Protective role of apolipoprotein A and B in Parkinson's disease: A prospective study from UK Biobank.}, journal = {Parkinsonism & related disorders}, volume = {132}, number = {}, pages = {107266}, doi = {10.1016/j.parkreldis.2025.107266}, pmid = {39798254}, issn = {1873-5126}, mesh = {Humans ; Male ; *Parkinson Disease/blood/epidemiology ; Female ; United Kingdom/epidemiology ; Aged ; Middle Aged ; Prospective Studies ; Biological Specimen Banks ; *Apolipoproteins A/blood ; *Apolipoprotein B-100/blood ; *Apolipoproteins B/blood ; UK Biobank ; }, abstract = {INTRODUCTION: Evidence have indicated relation between apolipoproteins and neurodegenerative disorders (NDDs). However, previous studies have produced inconsistent results, and a comprehensive analysis of apolipoproteins in NDDs is currently lacking.

METHODS: Using Cox proportional hazards regression analysis based on data from UK Biobank, we examined the association between baseline serum levels of apolipoprotein A (ApoA) and apolipoprotein B (ApoB) and risk of Parkinson's disease (PD), Alzheimer's disease, amyotrophic lateral sclerosis, frontotemporal dementia, and multiple sclerosis.

RESULTS: Elevated baseline levels of serum ApoA (HR = 0.84, 95 % CI: 0.71-0.99, P = 0.047) and ApoB (HR = 0.67, 95 % CI: 0.57-0.78, P = 3.18E-07) were associated with a reduced risk of incident PD. Subgroup analyses suggested the protective effect of serum ApoA was more significant for older participants and those with lower alcohol consumption, while higher serum ApoB was a more significant protective factor in males and those without stroke. No significant associations were found between apolipoproteins and other NDDs.

CONCLUSION: Increased baseline levels of serum ApoA and ApoB are linked to a lower risk of PD. These findings enhance understanding of the role of apolipoproteins in PD, and have implications for the development of therapeutic strategies in clinical trials.}, } @article {pmid39797438, year = {2025}, author = {Zeng, Y and Liu, M and Qian, H and Zhao, H and Fang, Y and Yu, Q and Bai, L and Pan, L}, title = {Investigating non-target site resistance to pyroxsulam in a glyphosate-resistant Lolium rigidum population.}, journal = {Pest management science}, volume = {81}, number = {6}, pages = {2751-2758}, doi = {10.1002/ps.8636}, pmid = {39797438}, issn = {1526-4998}, support = {//the National Key RandD Program of China (no. 2023YFD1401100)/ ; //National Natural Science Foundation of China (32372568 and 32130091)/ ; //Young Elite Scientists Sponsorship Program by CAST (2021QNRC001)/ ; //Earmarked Fund for China Agriculture Research System (CARS-16-E19)/ ; //Postgraduate Scientific Research Innovation Project of Hunan Province (QL20230088)/ ; //Scientific Research Fund of Hunan Provincial Education Department (23B0225)/ ; //National Natural Science Foundation of China (U23A20174)/ ; //Australian Grains and Research Development and Corporation (GRDC)/ ; }, mesh = {*Herbicide Resistance/genetics ; Glyphosate ; *Herbicides/pharmacology ; *Glycine/analogs & derivatives/pharmacology ; *Lolium/drug effects/genetics ; Acetolactate Synthase/antagonists & inhibitors/metabolism/genetics ; Acetyl-CoA Carboxylase/antagonists & inhibitors ; Plant Proteins/genetics/metabolism ; Isoxazoles ; Tetrazoles ; }, abstract = {BACKGROUND: Resistance to multiple herbicides is common in Lolium rigidum. Here, resistance to acetolactate synthase (ALS)- and susceptibility to acetyl-CoA carboxylase (ACCase)-inhibiting herbicides was confirmed in a glyphosate-resistant L. rigidum population (NLR70) from Australia and the mechanisms of pyroxsulam resistance were examined.

RESULTS: No ALS target-site mutations nor gene overexpression were detected. Cytochrome P450 monooxygenase (P450) and glutathione S-transferase (GST) inhibitors (indicators of some certain P450s or GSTs) did not significantly affect the resistance to pyroxsulam. Nevertheless, HPLC analysis showed that plants of the NLR70 population metabolized pyroxsulam faster than plants of the herbicide-susceptible population (SVLR1). RNA sequencing analysis and RT-qPCR validation confirmed that four P450s (CYP709B2, CYP72A14, CYP89A2, CYP94B3), one GT (UGT79), and one ABC transporter (ABCG41) genes were constitutively upregulated in NLR70 plants.

CONCLUSION: This study demonstrates that the glyphosate-resistant L. rigidum population (NLR70) also exhibits resistance to pyroxsulam and identifies six candidate genes associated with non-target site resistance to pyroxsulam. © 2025 Society of Chemical Industry.}, } @article {pmid39796536, year = {2024}, author = {Cuffaro, F and Lamminpää, I and Niccolai, E and Amedei, A}, title = {Nutritional and Microbiota-Based Approaches in Amyotrophic Lateral Sclerosis: From Prevention to Treatment.}, journal = {Nutrients}, volume = {17}, number = {1}, pages = {}, pmid = {39796536}, issn = {2072-6643}, support = {PNRR-MAD-2022-12375798//Ministero della Salute/ ; PE0000006//Ministry of University and Research (MUR)/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/prevention & control/therapy/microbiology/diet therapy ; Humans ; *Gastrointestinal Microbiome/physiology ; Probiotics ; Dysbiosis ; Prebiotics/administration & dosage ; Fecal Microbiota Transplantation ; Oxidative Stress ; Fatty Acids, Omega-3/administration & dosage ; }, abstract = {Metabolic alterations, including hypermetabolism, lipid imbalances, and glucose dysregulation, are pivotal contributors to the onset and progression of Amyotrophic Lateral Sclerosis (ALS). These changes exacerbate systemic energy deficits, heighten oxidative stress, and fuel neuroinflammation. Simultaneously, gastrointestinal dysfunction and gut microbiota (GM) dysbiosis intensify disease pathology by driving immune dysregulation, compromising the intestinal barrier, and altering gut-brain axis (GBA) signaling, and lastly advancing neurodegeneration. Therapeutic and preventive strategies focused on nutrition offer promising opportunities to address these interconnected pathophysiological mechanisms. Diets enriched with antioxidants, omega-3 fatty acids, and anti-inflammatory compounds-such as the Mediterranean diet-have shown potential in reducing oxidative stress and systemic inflammation. Additionally, microbiota-targeted approaches, including probiotics, prebiotics, postbiotics, and fecal microbiota transplantation, are emerging as innovative tools to restore microbial balance, strengthen gut integrity, and optimize GBA function. This review highlights the critical need for personalized strategies integrating immunonutrition and microbiota modulation to slow ALS progression, improve quality of life, and develop preventive measures for neurodegenerative and neuroinflammatory diseases. Future research should prioritize comprehensive dietary and microbiota-based interventions to uncover their therapeutic potential and establish evidence-based guidelines for managing ALS and related disorders.}, } @article {pmid39795334, year = {2024}, author = {Bhattacharya, S and Sen, MK and Hamouzová, K and Košnarová, P and Bharati, R and Menendez, J and Soukup, J}, title = {Pyroxsulam Resistance in Apera spica-venti: An Emerging Challenge in Crop Protection.}, journal = {Plants (Basel, Switzerland)}, volume = {14}, number = {1}, pages = {}, pmid = {39795334}, issn = {2223-7747}, support = {QL24010167//National Agency for Agricultural Research (NAZV)/ ; }, abstract = {Apera spica-venti, a prevalent weed in Czech winter wheat fields, has developed resistance to ALS-inhibiting herbicides due to their frequent use. This study reports a biotype of A. spica-venti resistant to pyroxsulam, with cross and multiple resistance to iodosulfuron, propoxycarbazone, pinoxaden, and chlortoluron. Dose-response experiments revealed high resistance of both R1 and R2 biotypes to pyroxsulam, with resistance factors (RF) of 6.69 and 141.65, respectively. Pre-treatment with malathion reduced RF by 2.40× and 1.25× in R1 and R2, indicating the potential involvement of cytochrome P450 (CytP450). NBD-Cl pre-treatment decreased RF only in R2, suggesting possible GST involvement. Gene analysis revealed no mutations (at previously reported sites) or overexpression in the acetolactate synthase (ALS) gene. However, a significant difference in ALS enzyme activity between resistant and susceptible biotypes points to target-site resistance mechanisms. Studies with [14]C-labeled pyroxsulam showed that reduced absorption and translocation were not likely resistance mechanisms. In summary, herbicide resistance in A. spica-venti appears to result from multiple mechanisms. Possible causes include target-site resistance from an unidentified ALS mutation (within coding or regulatory regions). Enhanced herbicide metabolism via CytP450s and GSTs is also a contributing factor. Further experimental validation is needed to confirm these mechanisms and fully understand the resistance. This evolution underscores the adaptive capacity of weed populations under herbicide pressure, emphasizing the need for alternative control strategies.}, } @article {pmid39794859, year = {2025}, author = {Niccolai, E and Di Gloria, L and Trolese, MC and Fabbrizio, P and Baldi, S and Nannini, G and Margotta, C and Nastasi, C and Ramazzotti, M and Bartolucci, G and Bendotti, C and Nardo, G and Amedei, A}, title = {Correction: Host genetics and gut microbiota influence lipid metabolism and inflammation: potential implications for ALS pathophysiology in SOD1G93A mice.}, journal = {Acta neuropathologica communications}, volume = {13}, number = {1}, pages = {5}, pmid = {39794859}, issn = {2051-5960}, } @article {pmid39794401, year = {2025}, author = {Cheng, J and Wu, BT and Liu, HP and Lin, WY}, title = {Machine learning identified novel players in lipid metabolism, endosomal trafficking, and iron metabolism of the ALS spinal cord.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {1564}, pmid = {39794401}, issn = {2045-2322}, support = {CMU110-MF-92//China Medical University, Taiwan/ ; CMU112-MF-62//China Medical University, Taiwan/ ; MOST 111-2314-B-039-017-MY3//National Science and Technology Council of Taiwan/ ; DMR-112-125//China Medical University Hospital, Taiwan/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/metabolism/genetics/pathology ; Humans ; *Iron/metabolism ; *Machine Learning ; *Lipid Metabolism/genetics ; *Spinal Cord/metabolism/pathology ; *Endosomes/metabolism ; Mitochondria/metabolism ; Motor Neurons/metabolism ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease affecting motor neurons. Although genes causing familial cases have been identified, those of sporadic ALS, which occupies the majority of patients, are still elusive. In this study, we adopted machine learning to build binary classifiers based on the New York Genome Center (NYGC) ALS Consortium's RNA-seq data of the postmortem spinal cord of ALS and non-neurological disease control. The accuracy of the classifiers was greater than 83% and 77% for the training set and the unseen test set, respectively. The classifiers contained 114 genes. Among them, 41 genes have been reported in previous ALS studies, and others are novel in this field. These genes are involved in mitochondrial respiration, lipid metabolism, endosomal trafficking, and iron metabolism, which may promote the progression of ALS pathology.}, } @article {pmid39793633, year = {2025}, author = {Baker, RS and Wang, JT and Rouatbi, N and Lu, Y and Al-Adhami, T and Asker, D and Rahman, KM and Al-Chalabi, A and Forbes, B and Bansal, S and Al-Jamal, KT}, title = {Brain distribution study of [[14]C]-Riluzole following intranasal administration in mice.}, journal = {International journal of pharmaceutics}, volume = {670}, number = {}, pages = {125195}, doi = {10.1016/j.ijpharm.2025.125195}, pmid = {39793633}, issn = {1873-3476}, mesh = {Animals ; Administration, Intranasal ; *Brain/metabolism ; Male ; Mice ; *Riluzole/administration & dosage/pharmacokinetics ; Tissue Distribution ; Tetrahydroisoquinolines/pharmacology/administration & dosage ; Acridines/pharmacology/administration & dosage ; Carbon Radioisotopes ; Biological Availability ; Blood-Brain Barrier/metabolism ; *Neuroprotective Agents/pharmacokinetics/administration & dosage ; }, abstract = {Amyotrophic lateral sclerosis (ALS) presents a substantial challenge due to its complex nature, limited effective treatment options, and modest benefits from current therapies in slowing disease progression. This study explores the potential of intranasal (IN) delivery to enhance the CNS delivery of riluzole (RLZ), a standard ALS treatment which is subject to blood-brain barrier efflux mechanisms. Additionally, the impact of elacridar (ELC), an efflux pump inhibitor, on IN RLZ CNS bioavailability was examined. To quantify RLZ in vivo in mice, [[14]C]-RLZ was synthesised using an optimised one-pot method. [[14]C]-RLZ yield was 21.3 ± 3.4 %, measured by High Performance Liquid Chromatography (HPLC), with a specific activity of 40.4 ± 3.9 µCi/mg measured by HPLC and liquid scintillation counting. RLZ synthesis was verified using proton nuclear magnetic resonance ([1]H NMR), and liquid chromatography-mass spectrometry. IN RLZ (5 mg/kg) produced double the maximum brain levels (1.11 ± 0.34 % Injected Dose (ID)/brain) at 30 min as oral RLZ (5 mg/kg). The uptake of RLZ in the liver was reduced by half for intranasal administration compared to oral administration. Intravenous ELC (5 mg/kg) substantially increased brain levels of IN RLZ to 3.52 ± 0.62 % ID/g brain at 60 min post-administration, compared to 1.87 ± 0.33 % ID/g brain in the absence of the efflux pump inhibitor. However, increased concentrations were also observed in the liver and blood. These results indicate that intranasal delivery of RLZ enhances brain targeting and reduces liver accumulation compared to the oral route. Brain uptake of IN RLZ was enhanced further by ELC, although not selectively as accumulation in the liver or blood was also observed. Further metabolic research using Chromatography-Mass spectrometry (LC-MS) or NMR along with excretion studies are warranted for a more comprehensive understanding of the pharmacokinetics of IN RLZ and IN RLZ/ELC. Additionally, employing suitable ALS animal models is crucial for understanding RLZ's effects on disease progression, mechanism of action, efficacy, and potential side effects to aid further development.}, } @article {pmid39792652, year = {2025}, author = {Mercadante, S and Petronaci, P and Lo Cascio, A}, title = {Living Will and Advance Care Planning in Patients With Amyotrophic Lateral Sclerosis Admitted to Specialistic Home Palliative Care.}, journal = {The American journal of hospice & palliative care}, volume = {}, number = {}, pages = {10499091241312906}, doi = {10.1177/10499091241312906}, pmid = {39792652}, issn = {1938-2715}, abstract = {Objectives: In Italy a recent law was approved for providing patients' wishes regarding end of life issues, commonly referred internationally to as "living wills", (Dichiarazione anticipata di trattamento, DAT). Regardless of this official document, advance care planning (ACP) is often used in a palliative care setting to share the treatments to start, to continue, to withdraw, thus preventing the stress on an acute decision. The aim of this study was to assess DAT and ACP in patients with amyotropic lateral sclerosis admitted to home palliative care. Methods: Patients consecutively admitted to speciliazed home palliative care were prospectively assessed. The presence of DAT or ACP was recorded. Results: Sixty-eight patients were enrolled in the period taken into consideration. No patient had drown up DAT, and only one patient provided his ACP prior to home palliative care admission. Along the course of home palliative care care assistance, 30.9% of patients provided their ACP. Discussion: In Italy DAT resulted scarcely widespread, despite an existing law, as no patient officially provided their indication on end of life issues. In addition, ACP was given only after starting specialized home palliative care in less than 1/3 of patients. Home palliative care seems to be a fundamental resource for improving communication and soliciting expression of patients' wishes regarding end of life issues.}, } @article {pmid39792557, year = {2025}, author = {Dykstra, MM and Weskamp, K and Gómez, NB and Waksmacki, J and Tank, E and Glineburg, MR and Snyder, A and Pinarbasi, E and Bekier, M and Li, X and Miller, MR and Bai, J and Shahzad, S and Nedumaran, N and Wieland, C and Stewart, C and Willey, S and Grotewold, N and McBride, J and Moran, JJ and Suryakumar, AV and Lucas, M and Tessier, PM and Ward, M and Todd, PK and Barmada, SJ}, title = {TDP43 autoregulation gives rise to dominant negative isoforms that are tightly controlled by transcriptional and post-translational mechanisms.}, journal = {Cell reports}, volume = {44}, number = {1}, pages = {115113}, pmid = {39792557}, issn = {2211-1247}, support = {F31 NS115257/NS/NINDS NIH HHS/United States ; K08 NS072233/NS/NINDS NIH HHS/United States ; I01 BX004842/BX/BLRD VA/United States ; P30 AG072931/AG/NIA NIH HHS/United States ; R01 NS099280/NS/NINDS NIH HHS/United States ; R01 NS113943/NS/NINDS NIH HHS/United States ; R01 NS097542/NS/NINDS NIH HHS/United States ; R56 NS128110/NS/NINDS NIH HHS/United States ; F31 NS134123/NS/NINDS NIH HHS/United States ; R35 GM136300/GM/NIGMS NIH HHS/United States ; }, mesh = {Humans ; Protein Isoforms/metabolism/genetics ; *DNA-Binding Proteins/metabolism/genetics ; Nonsense Mediated mRNA Decay ; Animals ; *Homeostasis ; HEK293 Cells ; *Transcription, Genetic ; *Protein Processing, Post-Translational ; Mice ; }, abstract = {The nuclear RNA-binding protein TDP43 is integrally involved in the pathogenesis of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Previous studies uncovered N-terminal TDP43 isoforms that are predominantly cytosolic in localization, prone to aggregation, and enriched in susceptible spinal motor neurons. In healthy cells, however, these shortened (s)TDP43 isoforms are difficult to detect in comparison to full-length (fl)TDP43, raising questions regarding their origin and selective regulation. Here, we show that sTDP43 is created as a by-product of TDP43 autoregulation and cleared by nonsense-mediated RNA decay (NMD). sTDP43-encoding transcripts that escape NMD are rapidly degraded post-translationally via the proteasome and macroautophagy. Circumventing these regulatory mechanisms by overexpressing sTDP43 results in neurodegeneration via N-terminal oligomerization and impairment of flTDP43 splicing activity, in addition to RNA-binding-dependent gain-of-function toxicity. Collectively, these studies highlight endogenous mechanisms that tightly regulate sTDP43 expression and underscore the consequences of aberrant sTDP43 accumulation in disease.}, } @article {pmid39792201, year = {2025}, author = {Fu, Z and Feng, B and Akogo, HY and Ma, J and Liu, Y and Quan, H and Zhang, X and Hou, Y and Zhang, X and Ma, J and Cui, H}, title = {Amyotrophic Lateral Sclerosis and Parkinson's Disease: Brain Tissue Transcriptome Analysis Reveals Interactions.}, journal = {Molecular neurobiology}, volume = {62}, number = {5}, pages = {6383-6396}, pmid = {39792201}, issn = {1559-1182}, support = {81801278//National Natural Science Foundation of China/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/genetics ; Humans ; *Parkinson Disease/genetics/metabolism ; *Brain/metabolism/pathology ; *Gene Expression Profiling/methods ; *Transcriptome/genetics ; Gene Regulatory Networks ; Protein Interaction Maps/genetics ; MicroRNAs/genetics/metabolism ; }, abstract = {This study utilises amyotrophic lateral sclerosis (ALS) and Parkinson's disease (PD) human brain samples from the GEO database and employs differential expression gene (DEG) analysis to identify genes that are pivotal in both neurodegenerative diseases. Through in depth GO and KEGG enrichment analyses, we elucidated the biological functions and potential pathways associated with these DEGs. Furthermore, by constructing protein‒protein interaction networks, we highlight the significance of shared DEGs in both cellular physiology and disease contexts. Analysis of drug‒gene associations revealed potential therapeutic compounds linked to ALS and PD treatment. Additionally, we explored the interactions between transcription factors, miRNAs, and common DEGs, revealing aspects of gene regulatory networks. This study provides insights into the molecular mechanisms of ALS and PD, offering valuable contributions to ongoing research and potential therapeutic avenues.}, } @article {pmid39791815, year = {2025}, author = {Rossi, A and Cuccioloni, M and Pellegrino, F and Giovannetti, R and Alladio, E}, title = {Discriminating Analysis of Metal Ions via Multivariate Curve Resolution-Alternating Least Squares Applied to Silver Nanoparticle Sensor.}, journal = {Nanomaterials (Basel, Switzerland)}, volume = {15}, number = {1}, pages = {}, pmid = {39791815}, issn = {2079-4991}, abstract = {Heavy metals are life-threatening pollutions because of their great toxicity, long-term persistence in nature and their bioaccumulation in living organisms. In this work, we performed multivariate curve resolution-alternating least squares analysis of UV-Vis raw spectra received by a colorimetric sensor constructed on mercaptoundecanoic acid functionalized silver nanoparticles (AgNPs@11MUA) to detect Cd[2+], Cu[2+], Mn[2+], Ni[2+], and Zn[2+] in water. This combined approach allowed the rapid identification and quantification of multiple heavy metals and showed adequate sensitivity and selectivity, thus representing a promising analytical and computational method for both laboratory and field applications such as environmental safety and public health monitoring.}, } @article {pmid39791748, year = {2025}, author = {Moss, KR and Saxena, S}, title = {Schwann Cells in Neuromuscular Disorders: A Spotlight on Amyotrophic Lateral Sclerosis.}, journal = {Cells}, volume = {14}, number = {1}, pages = {}, pmid = {39791748}, issn = {2073-4409}, support = {K22 NS125057/NS/NINDS NIH HHS/United States ; }, mesh = {*Schwann Cells/pathology/metabolism ; *Amyotrophic Lateral Sclerosis/pathology ; Humans ; Animals ; Neuromuscular Diseases/pathology ; Motor Neurons/pathology/metabolism ; Charcot-Marie-Tooth Disease/pathology ; }, abstract = {Amyotrophic Lateral Sclerosis (ALS) is a complex neurodegenerative disease primarily affecting motor neurons, leading to progressive muscle atrophy and paralysis. This review explores the role of Schwann cells in ALS pathogenesis, highlighting their influence on disease progression through mechanisms involving demyelination, neuroinflammation, and impaired synaptic function. While Schwann cells have been traditionally viewed as peripheral supportive cells, especially in motor neuron disease, recent evidence indicates that they play a significant role in ALS by impacting motor neuron survival and plasticity, influencing inflammatory responses, and altering myelination processes. Furthermore, advancements in understanding Schwann cell pathology in ALS combined with lessons learned from studying Charcot-Marie-Tooth disease Type 1 (CMT1) suggest potential therapeutic strategies targeting these cells may support nerve repair and slow disease progression. Overall, this review aims to provide comprehensive insights into Schwann cell classification, physiology, and function, underscoring the critical pathological contributions of Schwann cells in ALS and suggests new avenues for targeted therapeutic interventions aimed at modulating Schwann cell function in ALS.}, } @article {pmid39791705, year = {2024}, author = {Sun, D and Amiri, M and Meng, Q and Unnithan, RR and French, C}, title = {Calcium Signalling in Neurological Disorders, with Insights from Miniature Fluorescence Microscopy.}, journal = {Cells}, volume = {14}, number = {1}, pages = {}, pmid = {39791705}, issn = {2073-4409}, support = {DP170100363//Australian Research Council under Discovery Project/ ; }, mesh = {*Calcium Signaling ; Humans ; *Nervous System Diseases/metabolism/pathology ; Animals ; *Microscopy, Fluorescence/methods ; Calcium/metabolism ; Neurons/metabolism ; }, abstract = {Neurological disorders (NDs), such as amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and schizophrenia, represent a complex and multifaceted health challenge that affects millions of people around the world. Growing evidence suggests that disrupted neuronal calcium signalling contributes to the pathophysiology of NDs. Additionally, calcium functions as a ubiquitous second messenger involved in diverse cellular processes, from synaptic activity to intercellular communication, making it a potential therapeutic target. Recently, the development of the miniature fluorescence microscope (miniscope) enabled simultaneous recording of the spatiotemporal calcium activity from large neuronal ensembles in unrestrained animals, providing a novel method for studying NDs. In this review, we discuss the abnormalities observed in calcium signalling and its potential as a therapeutic target for NDs. Additionally, we highlight recent studies that utilise miniscope technology to investigate the alterations in calcium dynamics associated with NDs.}, } @article {pmid39791335, year = {2025}, author = {Dogan, EO and Simonini, SR and Bouley, J and Weiss, A and Brown, RH and Henninger, N}, title = {Genetic Ablation of Sarm1 Mitigates Disease Acceleration after Traumatic Brain Injury in the SOD1[G93A] Transgenic Mouse Model of Amyotrophic Lateral Sclerosis.}, journal = {Annals of neurology}, volume = {97}, number = {5}, pages = {963-975}, pmid = {39791335}, issn = {1531-8249}, support = {R21 NS131756/NS/NINDS NIH HHS/United States ; NS131756/NS/NINDS NIH HHS/United States ; //Moloney Fellowship/ ; //Angel Fund for ALS Research/ ; }, mesh = {Animals ; *Amyotrophic Lateral Sclerosis/genetics/pathology ; Mice ; Mice, Transgenic ; *Armadillo Domain Proteins/genetics/deficiency ; Disease Models, Animal ; *Cytoskeletal Proteins/genetics/deficiency ; *Superoxide Dismutase-1/genetics ; Male ; *Brain Injuries, Traumatic/genetics/complications/pathology ; Female ; Mice, Knockout ; Disease Progression ; }, abstract = {OBJECTIVE: Approximately 20% of familial cases of amyotrophic lateral sclerosis (ALS) are caused by mutations in the gene encoding superoxide dismutase 1 (SOD1). Epidemiological data have identified traumatic brain injury (TBI) as an exogenous risk factor for ALS; however, the mechanisms by which TBI may worsen SOD1 ALS remain largely undefined.

METHODS: We sought to determine whether repetitive TBI (rTBI) accelerates disease onset and progression in the transgenic SOD1[G93A] mouse ALS model, and whether loss of the primary regulator of axonal degeneration sterile alpha and TIR motif containing 1 (Sarm1) mitigates the histological and behavioral pathophysiology. We subjected wild-type (n = 23), Sarm1 knockout (KO; n = 17), SOD1[G93A] (n = 19), and SOD1[G93A]xSarm1[KO] (n = 26) mice of both sexes to rTBI or sham surgery at age 64 days (62-68 days). Body weight and ALS-deficit score were serially assessed up to 17 weeks after surgery and histopathology assessed in layer V of the primary motor cortex at the study end point.

RESULTS: In sham injured SOD1[G93A] mice, genetic ablation of Sarm1 did not attenuate axonal loss, improve neurological deficits, or survival. The rTBI accelerated onset of G93A-SOD1 ALS, as indicated by accentuated body weight loss, earlier onset of hindlimb tremor, and shortened survival. The rTBI also triggered TDP-43 mislocalization, enhanced axonal and neuronal loss, microgliosis, and astrocytosis. Loss of Sarm1 significantly diminished the impact of rTBI on disease progression and rescued rTBI-associated neuropathology.

INTERPRETATION: SARM1-mediated axonal death pathway promotes pathogenesis after TBI in SOD1[G93A] mice suggesting that anti-SARM1 therapeutics are a viable approach to preserve neurological function in injury-accelerated G93A-SOD1 ALS. ANN NEUROL 2025;97:963-975.}, } @article {pmid39789167, year = {2025}, author = {Kassubek, J and Roselli, F and Witzel, S and Dorst, J and Ludolph, AC and Rasche, V and Vernikouskaya, I and Müller, HP}, title = {Hypothalamic atrophy in primary lateral sclerosis, assessed by convolutional neural network-based automatic segmentation.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {1551}, pmid = {39789167}, issn = {2045-2322}, mesh = {Humans ; Female ; Male ; *Hypothalamus/pathology/diagnostic imaging ; Middle Aged ; *Neural Networks, Computer ; *Magnetic Resonance Imaging/methods ; *Atrophy/pathology ; Aged ; *Amyotrophic Lateral Sclerosis/pathology/diagnostic imaging ; Adult ; Motor Neuron Disease/pathology/diagnostic imaging ; Image Processing, Computer-Assisted/methods ; Case-Control Studies ; }, abstract = {Primary lateral sclerosis (PLS) is a motor neuron disease (MND) which mainly affects upper motor neurons. Within the MND spectrum, PLS is much more slowly progressive than amyotrophic laterals sclerosis (ALS). `Classical` ALS is characterized by catabolism and abnormal energy metabolism preceding onset of motor symptoms, and previous studies indicated that the disease progression of ALS involves hypothalamic atrophy. Very limited weight loss is observed in patients with PLS, which raises the question of whether there are also less hypothalamic alterations. The purpose of this study was to quantitatively investigate the hypothalamic volume in a group of PLS patients and to compare it with ALS and controls. Recently, we have introduced automatic hypothalamic quantification method based on the use of convolutional neural network (CNN) to reduce human variability and enhance analysis robustness. This CNN of U-Net architecture was applied for automatic segmentation of the hypothalamus and intracranial volume (ICV) to allow adjustments of the hypothalamic volume between subjects with different head sizes respectively. Automatic segmentation and volumetric analysis were performed in high resolution T1 weighted MRI volumes (acquired on a 1.5 T MRI scanner) of 46 PLS patients in comparison to 107 healthy controls and 411 `classical` ALS patients, respectively. Significant hypothalamic volume reduction was observed in PLS (818 ± 73 mm[3]) when compared to controls (852 ± 77 mm[3]); significant hypothalamic volume reduction was also confirmed in ALS (823 ± 84 mm[3]), in support of previous studies. No significant differences were found in normalized hypothalamic volumes between ALS patients and PLS patients at the group level. This unbiased CNN-based hypothalamus volume quantification study demonstrated similarly reduced hypothalamus volume in PLS and ALS patients, despite the clinical phenotypic differences.}, } @article {pmid39788313, year = {2025}, author = {Cassina, P and Miquel, E and Martínez-Palma, L and Cassina, A}, title = {Mitochondria and astrocyte reactivity: Key mechanism behind neuronal injury.}, journal = {Neuroscience}, volume = {567}, number = {}, pages = {227-234}, doi = {10.1016/j.neuroscience.2024.12.058}, pmid = {39788313}, issn = {1873-7544}, mesh = {Animals ; Humans ; *Astrocytes/metabolism/pathology ; *Mitochondria/metabolism ; *Neurons/metabolism/pathology ; }, abstract = {In this special issue to celebrate the 30th anniversary of the Uruguayan Society for Neuroscience (SNU), we find it pertinent to highlight that research on glial cells in Uruguay began almost alongside the history of SNU and contributed to the understanding of neuron-glia interactions within the international scientific community. Glial cells, particularly astrocytes, traditionally regarded as supportive components in the central nervous system (CNS), undergo notable morphological and functional alterations in response to neuronal damage, a phenomenon referred to as glial reactivity. Among the myriad functions of astrocytes, metabolic support holds significant relevance for neuronal function, given the high energy demand of the nervous system. Although astrocytes are typically considered to exhibit low mitochondrial respiratory chain activity, they possess a noteworthy mitochondrial network. Interestingly, both the morphology and activity of these organelles change following glial reactivity. Despite receiving less attention compared to studies on neuronal mitochondria, recent studies indicate that mitochondria play a crucial role in driving the transition of astrocytes from a quiescent to a reactive state in various neurological disorders. Notably, stimulating mitochondria in astrocytes has been shown to reduce damage associated with the neurodegenerative disease amyotrophic lateral sclerosis. Here, we focus on studies supporting the emerging paradigm that metabolic reprogramming occurs in astrocytes following damage, which is associated with their phenotypic shift to a new functional state that significantly influences the progression of pathology. Thus, exploring mitochondrial activity and metabolic reprogramming within glial cells may provide valuable insights for developing innovative therapeutic approaches to mitigate neuronal damage. In this review, we focus on studies supporting the emerging paradigm that metabolic reprogramming occurs in astrocytes following damage, which is associated with their phenotypic shift to a new functional state that significantly influences the progression of pathology. Thus, exploring mitochondrial activity and metabolic reprogramming within glial cells may provide valuable insights for developing innovative therapeutic approaches to mitigate neuronal damage.}, } @article {pmid39786806, year = {2025}, author = {Yang, S and Song, J and Deng, M and Cheng, S}, title = {Identification of Drug-Targetable Genes for Eczema and Dermatitis Using Integrated Genomic and Proteomic Approaches.}, journal = {Dermatitis : contact, atopic, occupational, drug}, volume = {36}, number = {4}, pages = {369-381}, doi = {10.1089/derm.2024.0429}, pmid = {39786806}, issn = {2162-5220}, mesh = {Humans ; *Eczema/genetics/drug therapy ; Proteomics ; Polymorphism, Single Nucleotide ; Genome-Wide Association Study ; Quantitative Trait Loci ; Mendelian Randomization Analysis ; Genomics ; *Dermatitis/genetics/drug therapy ; }, abstract = {Background: Eczema and dermatitis are common inflammatory skin conditions with significant morbidity. Identifying drug-targetable genes can facilitate the development of effective treatments. Methods: This study analyzed data obtained by meta-analysis of 2 genome-wide association studies on eczema/dermatitis (57,311 cases and 896,779 controls, European ancestry). We identified drug-targetable genes from the Drug-Gene Interaction Database and Finan et al's findings. Cis-expression quantitative trait loci (eQTL) data from human blood and skin tissues were used for Mendelian randomization (MR) analysis. Bayesian colocalization, proteomic MR, and meta-analysis validated the causal relationships. Finally, protein-protein interactions (PPIs) and correlation analysis of potential drug targets and cytokines were performed. Results: We identified 2532 drug-targetable genes; 3378 Single Nucleotide Polymorphism (SNPs) were associated with 1531 genes in blood cis-eQTLs, 664 SNPs with 667 genes in sun-exposed skin eQTLs, and 572 SNPs with 574 genes in nonsun-exposed skin eQTLs. Five genes (SLC22A5, NOTCH4, AGER, HLA-DRB5, and EHMT2) showed causal relationships with eczema/dermatitis across multiple datasets. Single-variable and multi-variable Mendelian randomization (SMR) and multi-SNP SMR analysis identified 8 genes (PIK3R4, DHODH, CXCR2, Interleukin (IL)18, LGALS9, RPS6KB2, SLC22A5, and AGER) across all tissues. Functional Summary Information for Variants in the Online Network (FUSION) analysis confirmed associations for SLC22A5 and AGER. Bayesian colocalization indicated AGER (PPH4: 0.95) as a shared causal variant. Proteomic MR and meta-analysis showed that increased AGER protein levels were associated with a lower risk of eczema or dermatitis (odds ratio: 0.995, 95% confidence interval: 0.997-0.993, P = 0.0002). A PPI network revealed interactions of AGER with NOTCH4 and multiple cytokines, whereas SLC22A5 showed no cytokine interactions. Conclusions: This study identified potential drug-targetable genes, with AGER showing strong potential as a target for reducing eczema/dermatitis risk. These findings provide a basis for developing targeted therapies.}, } @article {pmid39786727, year = {2025}, author = {Midgley, SD and Bariami, S and Habgood, M and Mackey, M}, title = {Adaptive Lambda Scheduling: A Method for Computational Efficiency in Free Energy Perturbation Simulations.}, journal = {Journal of chemical information and modeling}, volume = {65}, number = {2}, pages = {512-516}, pmid = {39786727}, issn = {1549-960X}, mesh = {Thermodynamics ; Ligands ; *Proteins/chemistry/metabolism ; Protein Binding ; }, abstract = {Recent increases in the availability of computational power have improved the accessibility of ligand-protein relative binding free energy (RBFE) calculations; however, these calculations remain resource-intensive, which can limit their practical application. RBFE calculations typically use a set of thermodynamic intermediates mediated by the transformation coordinate λ. Optimizing λ offers a way to tune the computational efforts required for a given RBFE calculation. Here, we present Adaptive Lambda Scheduling (ALS), a streamlined approach for on-the-fly bespoke λ scheduling. We show it can achieve substantial reductions in computational cost while retaining predictive performance.}, } @article {pmid39786321, year = {2025}, author = {Kim, K and Kim, S and Katana, M and Terentyev, D and Radwański, PB and Munger, MA}, title = {Riluzole is associated with reduced risk of heart failure.}, journal = {European journal of neurology}, volume = {32}, number = {1}, pages = {e70033}, pmid = {39786321}, issn = {1468-1331}, support = {R01HL14488/HL/NHLBI NIH HHS/United States ; R01 NS121234/NS/NINDS NIH HHS/United States ; R01 HL166604/HL/NHLBI NIH HHS/United States ; R01 HL155378/HL/NHLBI NIH HHS/United States ; R01HL166604/HL/NHLBI NIH HHS/United States ; R01HL155378/HL/NHLBI NIH HHS/United States ; }, mesh = {*Riluzole/therapeutic use ; Humans ; *Heart Failure/epidemiology/drug therapy ; Male ; Female ; Aged ; Middle Aged ; Incidence ; Amyotrophic Lateral Sclerosis/epidemiology/drug therapy ; Aged, 80 and over ; Cohort Studies ; United States/epidemiology ; }, abstract = {BACKGROUND: Reduction of intracellular Na[+] accumulation through late Na[+] current inhibition has been recognized as a target for cardiac Ca[2+] handling which underlies myocardial contractility and relaxation in heart failure (HF). Riluzole, an Na[+] channel blocker with enhancement of Ca[2+]-activated K[+] channel function, used for management of amyotrophic lateral sclerosis (ALS), is effective in suppressing Ca[2+] leak and therefore may improve cardiac function.

OBJECTIVES: The study aim was to investigate whether riluzole lowers HF incidence.

METHODS: Rates of HF incident were compared using a commercial insurance and Medicare supplement claims databases. Patients with a filled riluzole prescription (treatment) between 06/2009 and 12/2019 were compared to those with no-riluzole (control). We excluded HF patients during the 180-day baseline period. Study endpoint was the first HF diagnosis from the index riluzole prescription or ALS diagnosis. HF onset was compared between the propensity score matched treatment and control cohorts.

RESULTS: The matched cohort consisted of 4060 pairs of riluzole/control patients. The 24-month cumulative incidence of HF onset for riluzole versus control patients was 4.96% versus 7.27%, calculating hazard ratio (HR) [95% CI, p-value] of 0.55 [0.40-0.76, p < 0.01]. The HR estimates favoring riluzole over the ALS control were consistent across the 3 months to 2-year follow-up. The clinically and statistically significant effect on HF onset was driven by the lower rate of HFrEF with the 2-year HR [95% CI] of 0.46 [0.21-0.99].

CONCLUSIONS: Riluzole is associated with a lower rate of HF onset, suggesting a potential prevention strategy for early management.}, } @article {pmid39786151, year = {2025}, author = {Harrison, J and Bhardwaj, A and Houck, O and Sather, K and Sekiya, A and Knack, S and Saarunya Clarke, G and Puskarich, MA and Tignanelli, C and Rogers, L and Marmor, S and Beilman, G}, title = {Emergency medical services level of training is associated with mortality in trauma patients: A combined prehospital and in hospital database analysis.}, journal = {The journal of trauma and acute care surgery}, volume = {98}, number = {3}, pages = {402-409}, pmid = {39786151}, issn = {2163-0763}, mesh = {Humans ; Male ; Female ; *Wounds and Injuries/mortality/therapy ; Middle Aged ; Adult ; Aged ; *Emergency Medical Services/statistics & numerical data ; Adolescent ; Trauma Centers/statistics & numerical data ; Aged, 80 and over ; Databases, Factual ; Young Adult ; Propensity Score ; Retrospective Studies ; Hospital Mortality ; }, abstract = {BACKGROUND: There is conflicting evidence regarding emergency medical service (EMS) provider level of training and outcomes in trauma. We hypothesized that advanced life support (ALS) provider transport is associated with lower mortality compared with basic life support transport.

METHODS: We performed secondary analysis of a combined prehospital and in-hospital database of trauma patients utilizing ESO electronic medical records from 2018 to 2022. We included encounters with patients aged 15 years to 100 years transported by ground to a Level I or II trauma center with trauma-specific ICD-10-CM codes. Patients dead upon EMS arrival and transfers were excluded. We matched patients using 1:1 nearest neighbor propensity scores based on demographic, injury, and EMS characteristics, prehospital vitals, and trauma center designation. The exposure variable was EMS level of training and outcome was mortality. We conducted subgroup analyses on predefined cohorts (age > 50 years, mechanism of injury, prehospital EMS time > 30 minutes).

RESULTS: We identified 30,735 ALS and 1,758 basic life support encounters, representing 1,154 pairs following propensity matching. Mortality was lower among patients transported by ALS providers (odds ratio [OR], 0.40; 95% confidence interval [CI], 0.18-0.88; p = 0.023). Mortality was also lower in the subgroups of patients aged > 50 years (OR, 0.35; 95% CI, 0.13-0.98; p = 0.046), and in patients with mechanisms of injury excluding falls (OR, 0.35; 95% CI, 0.13-0.98; p = 0.047). In those with prolonged prehospital time, the association approached significance (OR, 0.30; 95% CI, 0.08-1.08; p = 0.067). In those with mechanisms of injury of fall, the association was not significant.

CONCLUSION: In this retrospective, propensity matched cohort study using a national sample of trauma patients, attendance by ALS providers was associated with reduced mortality. This was observed in the entire cohort, in those aged > 50 years, and those with a higher-risk mechanism of injury. It approached significance in those with prolonged prehospital time.

LEVEL OF EVIDENCE: Therapeutic/Care Management; Level III.}, } @article {pmid39783196, year = {2025}, author = {Lee, I and Mitsumoto, H and Lee, S and Kasarskis, E and Rosenbaum, M and Factor-Litvak, P and Nieves, JW}, title = {Interaction between riluzole treatment and dietary glycemic index in the disease progression of amyotrophic lateral sclerosis.}, journal = {Annals of clinical and translational neurology}, volume = {12}, number = {3}, pages = {491-498}, pmid = {39783196}, issn = {2328-9503}, support = {K23 NS131586/NS/NINDS NIH HHS/United States ; K23NS131586/NS/NINDS NIH HHS/United States ; }, mesh = {Aged ; Female ; Humans ; Male ; Middle Aged ; *Amyotrophic Lateral Sclerosis/drug therapy/physiopathology ; Cohort Studies ; *Disease Progression ; *Glycemic Index/physiology ; *Neuroprotective Agents/pharmacology/administration & dosage ; *Riluzole/pharmacology/administration & dosage ; }, abstract = {OBJECTIVE: We examined whether riluzole treatment modifies the associations between the dietary glycemic index (GI) and load (GL) and disease progression in amyotrophic lateral sclerosis (ALS).

METHODS: Sporadic ALS patients in the Multicenter Cohort Study of Oxidative Stress who completed a baseline food frequency questionnaire were included (n = 304). Interactions between baseline riluzole treatment and GI/GL on functional decline and tracheostomy-free survival were examined using linear regression and Cox proportional hazard models adjusted for covariates. Age, sex, disease duration, diagnostic certainty, body mass index, bulbar onset, revised ALS functional rating scale (ALSFRS-r) total score, and forced vital capacity, from baseline were included as covariates.

RESULTS: Baseline higher GI and GL were associated with less decline of ALSFRS-r total score at 3-month follow-up in the riluzole treatment group (RTG) but not in the no-riluzole group (NRG). When quartile groups were used, GI second [β = -1.9, 95% CI (-4.1, -0.2), p = 0.07], third [β = -3.0, 95% CI (-5.1, -0.8), p < 0.01] and fourth [β = -2.2, 95% CI (-4.3, -0.01), p < 0.05] quartile groups were associated with less ALSFRS-r decline at 3-months compared to the first quartile group (GI < 47.2) among the RTG. Similarly, GL fourth quartile group (GL > 109.5) was associated with less ALSFRS-r decline at 3 months compared to the first quartile group [β = -2.6, 95% CI (-4.7, -0.5), p < 0.05] among the RTG. In NRG, no statistically significant differences in ALSFRS-r decline were found among GI/GL quartile groups.

INTERPRETATION: High dietary GI and GL are associated with a slower functional decline only among ALS patients taking riluzole.}, } @article {pmid39783194, year = {2025}, author = {Smith, SE and McCoy-Gross, K and Malcolm, A and Oranski, J and Markway, JW and Miller, TM and Bucelli, RC}, title = {Tofersen treatment leads to sustained stabilization of disease in SOD1 ALS in a "real-world" setting.}, journal = {Annals of clinical and translational neurology}, volume = {12}, number = {2}, pages = {311-319}, pmid = {39783194}, issn = {2328-9503}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy/genetics ; Male ; Middle Aged ; Female ; *Superoxide Dismutase-1/genetics ; Aged ; Neurofilament Proteins/blood/cerebrospinal fluid ; Adult ; Disease Progression ; *Outcome Assessment, Health Care ; }, abstract = {OBJECTIVE: Patients with amyotrophic lateral sclerosis (ALS) caused by superoxide dismutase 1 (SOD1) gene mutations (SOD1 ALS) treated with tofersen have shown slowing of disease progression, and disease stabilization with recovery of function in some patients. We report our clinical experience with treating patients with SOD1 ALS and the effects of tofersen on outcome measures.

METHODS: This was a single-center observational study of patients with SOD1 ALS receiving treatment with tofersen. The effects of tofersen treatment on neurofilament levels, muscle strength, and clinical outcome measures were assessed. Several patients had outpatient neuromuscular rehabilitation in addition to tofersen treatment and we report changes in functional outcomes.

RESULTS: Seven SOD1 ALS patients received treatment at our institution. All patients showed robust and sustained declines in serum NfL and CSF pNFH (mean change serum NfL: -57.9%; mean change CSF pNFH: -67.6%). There was apparent disease stabilization as assessed by the ALSFRS-R total score, mean change 1.1 (SD = 0.7). There was notable improvement in functional independence measured by the FIM motor score, mean change 5.13 points (SD = 3.85).

INTERPRETATION: This study provides evidence that tofersen treatment in SOD1 ALS can lead to meaningful preservation of function and suggestions of sustained improvement in neurologic function in some patients, and strongly supports the role of neurofilaments as therapeutic biomarkers.}, } @article {pmid39779800, year = {2025}, author = {Regondi, S and Donvito, G and Frontoni, E and Kostovic, M and Minazzi, F and Bratières, S and Filosto, M and Pugliese, R}, title = {Artificial intelligence empowered voice generation for amyotrophic lateral sclerosis patients.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {1361}, pmid = {39779800}, issn = {2045-2322}, mesh = {*Amyotrophic Lateral Sclerosis/physiopathology/therapy/complications/psychology ; Humans ; *Artificial Intelligence ; *Voice ; Female ; Male ; Middle Aged ; *Quality of Life ; Aged ; Communication Aids for Disabled ; Speech/physiology ; Adult ; }, abstract = {Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease that can result in a progressive loss of speech due to bulbar dysfunction, which can have significant negative impact on the patient's mental well-being. Alternative Augmentative Communication (AAC) strategies based on synthetic voices have been shown to assist patients in maintaining communication and improving their Quality of Life (QoL). However, such synthetic voices are often perceived as impersonal and fail to capture the unique voice and identity of the patient. To tackle this issue, combining voice banking (VB) and artificial intelligence (AI) has emerged as a more natural communication strategy, enabling individuals to preserve their voice for use with AAC devices as needed. This involves recording speech samples to generate a synthetic voice closely resembling the individual's own. Despite the increasing interest in VB, there's a lack of clear strategies for its effective implementation in rapidly progressing diseases like ALS. Additionally, the perceptual quality of VB on patients with preserved speech, especially when offered early in the disease, remains poorly understood. In light of these challenges, this study aims to assess the effectiveness and the perceptual impact of AI-generated voices on ALS patients with preserved speech, utilizing a personalized voice synthesis system based on machine learning. The AI-generated patient-specific voice is achieved through voice recording, followed by fine-tuning using a Generative Adversarial Network for Efficient and High Fidelity Speech Synthesis (HiFi-GAN), resulting in a model capable of producing speech highly similar to the patient's own voice, with exceptional expressive and audio quality. By addressing these aspects, this study intends to offer valuable insights into the potential benefits and challenges of combining VB with AI voices to enhance communication support for ALS patients.}, } @article {pmid39779704, year = {2025}, author = {Kempthorne, L and Vaizoglu, D and Cammack, AJ and Carcolé, M and Roberts, MJ and Mikheenko, A and Fisher, A and Suklai, P and Muralidharan, B and Kroll, F and Moens, TG and Yshii, L and Verschoren, S and Hölbling, BV and Moreira, FC and Katona, E and Coneys, R and de Oliveira, P and Zhang, YJ and Jansen, K and Daughrity, LM and McGown, A and Ramesh, TM and Van Den Bosch, L and Lignani, G and Rahim, AA and Coyne, AN and Petrucelli, L and Rihel, J and Isaacs, AM}, title = {Dual-targeting CRISPR-CasRx reduces C9orf72 ALS/FTD sense and antisense repeat RNAs in vitro and in vivo.}, journal = {Nature communications}, volume = {16}, number = {1}, pages = {459}, pmid = {39779704}, issn = {2041-1723}, support = {/WT_/Wellcome Trust/United Kingdom ; 217150/Z/19/Z//Wellcome Trust (Wellcome)/ ; 648716 - C9ND//EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council)/ ; }, mesh = {*C9orf72 Protein/genetics/metabolism ; *Amyotrophic Lateral Sclerosis/genetics/metabolism/therapy ; Humans ; *Frontotemporal Dementia/genetics/metabolism ; Animals ; *CRISPR-Cas Systems ; *RNA, Antisense/genetics ; Mice ; HEK293 Cells ; *Induced Pluripotent Stem Cells/metabolism ; DNA Repeat Expansion/genetics ; Disease Models, Animal ; Neurons/metabolism ; Genetic Therapy/methods ; }, abstract = {The most common genetic cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) is an intronic G4C2 repeat expansion in C9orf72. The repeats undergo bidirectional transcription to produce sense and antisense repeat RNA species, which are translated into dipeptide repeat proteins (DPRs). As toxicity has been associated with both sense and antisense repeat-derived RNA and DPRs, targeting both strands may provide the most effective therapeutic strategy. CRISPR-Cas13 systems mature their own guide arrays, allowing targeting of multiple RNA species from a single construct. We show CRISPR-Cas13d variant CasRx effectively reduces overexpressed C9orf72 sense and antisense repeat transcripts and DPRs in HEK cells. In C9orf72 patient-derived iPSC-neuron lines, CRISPR-CasRx reduces endogenous sense and antisense repeat RNAs and DPRs and protects against glutamate-induced excitotoxicity. AAV delivery of CRISPR-CasRx to two distinct C9orf72 repeat mouse models significantly reduced both sense and antisense repeat-containing transcripts. This highlights the potential of RNA-targeting CRISPR systems as therapeutics for C9orf72 ALS/FTD.}, } @article {pmid39779681, year = {2025}, author = {McCallister, TX and Lim, CKW and Singh, M and Zhang, S and Ahsan, NS and Terpstra, WM and Xiong, AY and Zeballos C, MA and Powell, JE and Drnevich, J and Kang, Y and Gaj, T}, title = {A high-fidelity CRISPR-Cas13 system improves abnormalities associated with C9ORF72-linked ALS/FTD.}, journal = {Nature communications}, volume = {16}, number = {1}, pages = {460}, pmid = {39779681}, issn = {2041-1723}, support = {1R01NS123556-01A1//U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; 1U01NS122102-01A1//U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; 5R01GM141296//U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)/ ; MDA602798//Muscular Dystrophy Association (Muscular Dystrophy Association Inc.)/ ; R01 GM141296/GM/NIGMS NIH HHS/United States ; 20-IIP-516//Amyotrophic Lateral Sclerosis Association (ALS Association)/ ; T32 EB019944/EB/NIBIB NIH HHS/United States ; U01 NS122102/NS/NINDS NIH HHS/United States ; R01 NS123556/NS/NINDS NIH HHS/United States ; }, mesh = {*Amyotrophic Lateral Sclerosis/genetics/pathology/metabolism ; *C9orf72 Protein/genetics/metabolism ; *Frontotemporal Dementia/genetics/pathology/metabolism ; *CRISPR-Cas Systems ; Humans ; Animals ; DNA Repeat Expansion/genetics ; Disease Models, Animal ; Motor Neurons/metabolism/pathology ; Mice ; }, abstract = {An abnormal expansion of a GGGGCC (G4C2) hexanucleotide repeat in the C9ORF72 gene is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), two debilitating neurodegenerative disorders driven in part by gain-of-function mechanisms involving transcribed forms of the repeat expansion. By utilizing a Cas13 variant with reduced collateral effects, we develop here a high-fidelity RNA-targeting CRISPR-based system for C9ORF72-linked ALS/FTD. When delivered to the brain of a transgenic rodent model, this Cas13-based platform curbed the expression of the G4C2 repeat-containing RNA without affecting normal C9ORF72 levels, which in turn decreased the formation of RNA foci, reduced the production of a dipeptide repeat protein, and reversed transcriptional deficits. This high-fidelity system possessed improved transcriptome-wide specificity compared to its native form and mediated targeting in motor neuron-like cells derived from a patient with ALS. These results lay the foundation for the implementation of RNA-targeting CRISPR technologies for C9ORF72-linked ALS/FTD.}, } @article {pmid39779313, year = {2025}, author = {Xiao, Y and Tan, Y and Li, C and Wei, Q and Jiang, Q and Wang, S and Yang, T and Lin, J and Zhang, L and Shang, H}, title = {Genetic and clinical analysis of OPTN in amyotrophic lateral sclerosis.}, journal = {Journal of medical genetics}, volume = {62}, number = {4}, pages = {242-248}, doi = {10.1136/jmg-2024-109978}, pmid = {39779313}, issn = {1468-6244}, mesh = {Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; *Amyotrophic Lateral Sclerosis/genetics/pathology ; Asian People/genetics ; *Cell Cycle Proteins/genetics ; Genetic Association Studies ; *Genetic Predisposition to Disease ; Genotype ; *Membrane Transport Proteins/genetics ; Mutation ; Phenotype ; *Transcription Factor TFIIIA/genetics ; White People/genetics ; Cohort Studies ; }, abstract = {BACKGROUND: Considerable heterogeneity in genotypes and phenotypes has been observed among patients with amyotrophic lateral sclerosis (ALS) harbouring optineurin gene (OPTN) mutations, as reported in prior studies. The study aimed to elucidate the correlation between OPTN genotypes and phenotypes.

METHODS: OPTN gene variants were screened within a substantial Chinese cohort of patients with ALS, encompassing LoF and rare missense variants. Additionally, a systematic literature review was conducted to compile the spectrum of OPTN mutations and explore the relationship between the genotype and phenotype of patients with ALS with OPTN.

RESULTS: A total of 33 unrelated patients with ALS with 24 rare OPTN variants, including 17 novel variants, were identified in 2279 patients with ALS. Among 24 variants in our cohort and 106 variants in previous studies, only 33.3% and 35.8% were pathogenic/likely pathogenic variants. Moreover, the frequency of OPTN variants in the Asian ALS population was higher (1.08%) than that of the Caucasian population (0.55%). For the phenotype of patients with ALS carrying OPTN variants, we found that patients with pathogenic/likely pathogenic variants had the highest baseline progression rate and the shortest survival time among groups in our cohort.

CONCLUSION: Our study contributed to a broader understanding of the genotype and phenotype spectrum of patients with ALS carrying OPTN variants. Further investigations are warranted to definitively establish the genotype-phenotype associations.}, } @article {pmid39778888, year = {2025}, author = {Etxebeste-Mitxeltorena, M and Flores-Romero, H and Ramos-Inza, S and Masiá, E and Nenchova, M and Montesinos, J and Martinez-Gonzalez, L and Porras, G and Orzáez, M and Vicent, MJ and Gil, C and Area-Gomez, E and Garcia-Saez, AJ and Martinez, A}, title = {Modulation of Mitochondria-Endoplasmic Reticulum Contacts (MERCs) by Small Molecules as a New Strategy for Restoring Lipid Metabolism in an Amyotrophic Lateral Sclerosis Model.}, journal = {Journal of medicinal chemistry}, volume = {68}, number = {2}, pages = {1179-1194}, pmid = {39778888}, issn = {1520-4804}, support = {/ERC_/European Research Council/International ; }, mesh = {*Amyotrophic Lateral Sclerosis/metabolism/drug therapy ; Humans ; *Endoplasmic Reticulum/metabolism/drug effects ; *Mitochondria/metabolism/drug effects ; *Lipid Metabolism/drug effects ; *Small Molecule Libraries/pharmacology/chemistry ; Cholesterol/metabolism ; HCT116 Cells ; Mitochondria Associated Membranes ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease without effective treatment. The progressive motoneuron death in ALS is associated with alterations in lipid metabolism. As its regulation occurs in mitochondria-associated endoplasmic reticulum (ER) membranes (MAMs), modulation of mitochondria-ER contacts (MERCs) is emerging as a crucial factor in MAM formation and lipid metabolism control. Using the MERLIN biosensor in a high-throughput screening within the EU-OPENSCREEN ERIC, we discovered small molecules that increase MERCs in HCT116 cells, enhancing their ability to uptake cholesterol. We demonstrated that cholesterol trafficking is decreased in an ALS patient-derived cell model, and this trafficking is restored after treatment with the discovered MERC modulator 24. Electron microscopy revealed that treatment with compound 24 increases MERCs, promotes lipid droplet formation, and restores mitochondrial cristae. Overall, the brain-permeable MERC modulator, compound 24, may serve as a valuable pharmacological tool for studying MAM function and holds potential for in vivo studies in ALS and other MAM dysfunction diseases.}, } @article {pmid39778605, year = {2025}, author = {Urano, Y and Iwagaki, A and Takeishi, A and Uchiyama, N and Noguchi, N}, title = {Downregulation of the SREBP pathways and disruption of redox status by 25-hydroxycholesterol predispose cells to ferroptosis.}, journal = {Free radical biology & medicine}, volume = {228}, number = {}, pages = {319-328}, doi = {10.1016/j.freeradbiomed.2025.01.010}, pmid = {39778605}, issn = {1873-4596}, mesh = {*Ferroptosis/drug effects ; *Hydroxycholesterols/pharmacology/metabolism ; Animals ; Mice ; Oxidation-Reduction ; Phospholipid Hydroperoxide Glutathione Peroxidase/genetics/metabolism ; Signal Transduction ; *Schwann Cells/metabolism/drug effects/pathology ; Cell Line ; Down-Regulation ; Steroid Hydroxylases/genetics/metabolism ; *Sterol Regulatory Element Binding Proteins/metabolism/genetics ; Humans ; }, abstract = {Enzymatically formed side-chain oxysterols function as signaling molecules regulating cholesterol homeostasis and act as intermediates in the biosynthesis of bile acids. In addition to these physiological functions, an imbalance in oxysterol homeostasis has been implicated in pathophysiology. Cholesterol 25-hydroxylase (CH25H) and its product 25-hydroxycholesterol (25-OHC), also formed by autoxidation, are associated with amyotrophic lateral sclerosis. However, the effects of 25-OHC on cell viability in glial cells remain unclear. This study demonstrates that 25-OHC induces ferroptosis, an iron-dependent programmed cell death, in mouse Schwann IMS32 cells. Mechanistically, 25-OHC suppressed the expression of selenoprotein glutathione peroxidase 4 (GPX4) at both the transcriptional and translational levels by inhibiting the processing of sterol regulatory element-binding proteins (SREBPs). In addition, 25-OHC upregulated the expression of NADH-cytochrome b5 reductase 1 (CYB5R1) and NADPH-cytochrome P450 reductase (POR), enzymes that promote lipid peroxidation. We further found that 25-OHC increases the expression of glutathione-specific gamma-glutamylcyclotransferase 1 (CHAC1) and decreases glutathione levels. Importantly, non-cytotoxic concentrations of 25-OHC enhanced cellular sensitivity to ferroptosis inducers by downregulating GPX4 expression. These findings reveal a multifaceted approach whereby 25-OHC induces ferroptosis through SREBP pathway suppression and redox imbalance in mouse Schwann IMS32 cells.}, } @article {pmid39778593, year = {2025}, author = {Chen, Q and Chen, G and Wang, Q}, title = {Application of Network Pharmacology in the Treatment of Neurodegenerative Diseases with Traditional Chinese Medicine.}, journal = {Planta medica}, volume = {91}, number = {5}, pages = {226-237}, pmid = {39778593}, issn = {1439-0221}, support = {2023AFB677//the Natural Science Foundation of Hubei Province/ ; 2024AFB578//the Natural Science Foundation of Hubei Province/ ; 2023LYYYGZRP0003//the Intramural Research Program of Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology/ ; 2023LYYYSZRP0001//the Intramural Research Program of Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology/ ; }, mesh = {Humans ; *Medicine, Chinese Traditional/methods ; *Neurodegenerative Diseases/drug therapy ; *Network Pharmacology/methods ; *Drugs, Chinese Herbal/pharmacology/therapeutic use ; }, abstract = {In recent years, the incidence of neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis, has exhibited a steadily rising trend, which has posed a major challenge to the global public health. Traditional Chinese medicine, with its multicomponent and multitarget characteristics, offers a promising approach to treating neurodegenerative diseases. However, comprehensively elucidating the complex mechanisms underlying traditional Chinese medicine formulations remains challenging. As an emerging systems biology method, network pharmacology has provided a vital tool for revealing the multitarget mechanisms of traditional Chinese medicine through high-throughput technologies, molecular docking, and network analysis. This paper reviews the advancements in the application of network pharmacology in treating neurodegenerative diseases using traditional Chinese medicine, analyzes the current status of relevant databases and technological methods, discusses the limitations, and proposes future directions to promote the modernization of traditional Chinese medicine and the development of precision medicine.}, } @article {pmid39778572, year = {2025}, author = {Je, Y and Park, YE and Shin, YB}, title = {Differentiating Inclusion Body Myositis From Amyotrophic Lateral Sclerosis Based on the Features of Dysphagia: Insights From a Patient With Rapidly Progressive Dysphagia.}, journal = {Journal of clinical neurology (Seoul, Korea)}, volume = {21}, number = {1}, pages = {83-85}, pmid = {39778572}, issn = {1738-6586}, support = {/PNUH/Pusan National University Hospital/Korea ; }, } @article {pmid39777244, year = {2025}, author = {Moura, FA and Siqueira, AIAN}, title = {Gut-liver axis in sepsis-associated liver injury: Epidemiology, challenges and clinical practice.}, journal = {World journal of gastroenterology}, volume = {31}, number = {1}, pages = {99987}, pmid = {39777244}, issn = {2219-2840}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Sepsis/complications/epidemiology ; *Dysbiosis ; *Liver/metabolism/pathology ; Animals ; *Oxidative Stress ; Bacterial Translocation ; Liver Diseases/epidemiology/microbiology ; Critical Illness ; Intensive Care Units/statistics & numerical data ; Anti-Bacterial Agents/therapeutic use ; }, abstract = {Although the liver has a remarkable regenerative capacity, sepsis-associated liver injury (SLI) is a complication often seen in intensive care units. Due to its role in immune and inflammatory regulation, the liver is particularly vulnerable during severe infections. Understanding the global prevalence, causes, and management of SLI is essential to improve outcomes and reduce healthcare costs. This paper aims to explore these factors, with an emphasis on identifying effective strategies for clinical management. Zhang et al's bibliometric analysis of 787 publications (745 original articles and 42 reviews, mostly in animal models) from 2000 to 2023 highlights the growing interest in SLI, focusing on oxidative stress, gut microbiota, and inflammatory processes. Key components such as nuclear factor-kappa B and the NOD-like receptor thermal protein domain associated protein 3 inflammasome pathway, along with their links to gut microbiota imbalance and oxidative stress, are crucial for understanding SLI pathogenesis. The gut-liver axis, particularly the role of intestinal permeability and bacterial translocation in liver inflammation, is emphasized. In this context, bacterial translocation is especially relevant for critically ill patients, as it can exacerbate liver inflammation. The findings underscore the need for integrated care in intensive care units, prioritizing gut health and careful antibiotic use to prevent dysbiosis. Despite extensive research, there remains a lack of clinical trials to validate therapeutic approaches. The abundance of experimental studies highlights potential therapeutic targets, stressing the need for high-quality randomized clinical trials to translate these findings into clinical practice.}, } @article {pmid39776752, year = {2024}, author = {Schwamburger, J and Brock, K and Cooper, R}, title = {The effect of GV-58, a calcium channel modifier, on synaptic transmission at the larval Drosophila and crayfish neuromuscular junctions.}, journal = {microPublication biology}, volume = {2024}, number = {}, pages = {}, pmid = {39776752}, issn = {2578-9430}, abstract = {GV-58 is known to increase the opening time of the mammalian P-type calcium channel in presynaptic motor nerve terminals. GV-58 is suggested as a therapeutic agent for dampening the symptoms of amyotrophic lateral sclerosis. To further understand the mechanisms of GV-58 actions, the Drosophila and crayfish neuromuscular junctions were used as models. Their presynaptic calcium channels are a P-type based on pharmacology profiles. However, exposure of GV-58 (1mM) did not produce any consistent alteration in synaptic transmission in these two preparations. It is possible that the molecular structure of the P-type channels is different in the Drosophila and crayfish.}, } @article {pmid39776251, year = {2025}, author = {Öijerstedt, L and Foucher, J and Lovik, A and Yazdani, S and Juto, A and Kläppe, U and Fang, F and Ingre, C}, title = {Correction: Repeated cognitive assessments show stable function over time in patients with ALS.}, journal = {Journal of neurology}, volume = {272}, number = {1}, pages = {104}, doi = {10.1007/s00415-024-12833-z}, pmid = {39776251}, issn = {1432-1459}, } @article {pmid39775908, year = {2025}, author = {de Vries, E and Hagbohm, C and Ouellette, R and Granberg, T}, title = {Clinical 7 Tesla magnetic resonance imaging: Impact and patient value in neurological disorders.}, journal = {Journal of internal medicine}, volume = {297}, number = {3}, pages = {244-261}, pmid = {39775908}, issn = {1365-2796}, mesh = {Humans ; *Magnetic Resonance Imaging/methods ; *Nervous System Diseases/diagnostic imaging ; Amyotrophic Lateral Sclerosis/diagnostic imaging ; }, abstract = {Magnetic resonance imaging (MRI) is a cornerstone of non-invasive diagnostics and treatment monitoring, particularly for diseases of the central nervous system. Although 1.5- and 3 Tesla (T) field strengths remain the clinical standard, the advent of 7 T MRI represents a transformative step forward, offering superior spatial resolution, contrast, and sensitivity for visualizing neuroanatomy, metabolism, and function. Recent innovations, including parallel transmission and deep learning-based reconstruction, have resolved many prior technical challenges of 7 T MRI, enabling its routine clinical use. This review examines the diagnostic impact, patient value, and practical considerations of 7 T MRI, emphasizing its role in facilitating earlier diagnoses and improving care in conditions, such as amyotrophic lateral sclerosis (ALS), epilepsy, multiple sclerosis (MS), dementia, parkinsonism, tumors, and vascular diseases. Based on insights from over 1200 clinical scans with a second-generation 7 T system, the review highlights disease-specific biomarkers such as the motor band sign in ALS and the new diagnostic markers in MS, the central vein sign, and paramagnetic rim lesions. The unparalleled ability of 7 T MRI to study neurological diseases ex vivo at ultra-high resolution is also explored, offering new opportunities to understand pathophysiology and identify novel treatment targets. Additionally, the review provides a clinical perspective on patient handling and safety considerations, addressing challenges and practicalities associated with clinical 7 T MRI. By bridging research and clinical practice, 7 T MRI has the potential to redefine neuroimaging and advance the understanding and management of complex neurological disorders.}, } @article {pmid39775401, year = {2025}, author = {Grassi, M and Tarantino, B}, title = {SEMdag: Fast learning of Directed Acyclic Graphs via node or layer ordering.}, journal = {PloS one}, volume = {20}, number = {1}, pages = {e0317283}, pmid = {39775401}, issn = {1932-6203}, mesh = {Humans ; *Algorithms ; *COVID-19 ; SARS-CoV-2 ; Breast Neoplasms ; Software ; }, abstract = {A Directed Acyclic Graph (DAG) offers an easy approach to define causal structures among gathered nodes: causal linkages are represented by arrows between the variables, leading from cause to effect. Recently, industry and academics have paid close attention to DAG structure learning from observable data, and many techniques have been put out to address the problem. We provide a two-step approach, named SEMdag(), that can be used to quickly learn high-dimensional linear SEMs. It is included in the R package SEMgraph and employs a two-stage order-based search using previous knowledge (Knowledge-based, KB) or data-driven method (Bottom-up, BU), under the premise that a linear SEM with equal variance error terms is assumed. We evaluated our framework's for finding plausible DAGs against six well-known causal discovery techniques (ARGES, GES, PC, LiNGAM, CAM, NOTEARS). We conducted a series of experiments using observed expression (or RNA-seq) data, taking into account a pair of training and testing datasets for four distinct diseases: Amyotrophic Lateral Sclerosis (ALS), Breast cancer (BRCA), Coronavirus disease (COVID-19) and ST-elevation myocardial infarction (STEMI). The results show that the SEMdag() procedure can recover a graph structure with good disease prediction performance evaluated by a conventional supervised learning algorithm (RF): in the scenario where the initial graph is sparse, the BU approach may be a better choice than the KB one; in the case where the graph is denser, both BU an KB report high performance, with highest score for KB approach based on topological layers. Besides its superior disease predictive performance compared to previous research, SEMdag() offers the user the flexibility to define distinct structure learning algorithms and can handle high dimensional issues with less computing load. SEMdag() function is implemented in the R package SEMgraph, easily available at https://CRAN.R-project.org/package=SEMgraph.}, } @article {pmid39774976, year = {2025}, author = {Naito, H and Nakamori, M and Toko, M and Hayashi, Y and Tazuma, T and Watanabe, T and Ishihara, K and Tachiyama, K and Yamazaki, Y and Maruyama, H}, title = {A single-center, single-arm, prospective, open-label, and comparative trial to evaluate the safety and tolerability profile of a 90-day oral L-arginine hydrochloride intervention for patients with amyotrophic lateral sclerosis.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {1120}, pmid = {39774976}, issn = {2045-2322}, support = {23K16642//Japan Society for the Promotion of Science/ ; NA//ALS Foundation, Japan ALS Association/ ; }, mesh = {Aged ; Female ; Humans ; Male ; Middle Aged ; Administration, Oral ; *Amyotrophic Lateral Sclerosis/drug therapy ; *Arginine/administration & dosage/adverse effects/therapeutic use ; Nutritional Status ; Prospective Studies ; Treatment Outcome ; }, abstract = {Weight loss, a key indicator of malnutrition in amyotrophic lateral sclerosis (ALS) patients, negatively impacts patient prognosis. However, effective nutritional interventions have not been adequately established. Research in ALS model mice has shown that L-arginine can prolong survival; however, no human intervention studies have been conducted. We conducted a single-center, single-arm, prospective, open-label, and comparative trial to assess the safety and tolerability of L-arginine hydrochloride in ALS patients. ALS patients were administered 15 g/day L-arginine hydrochloride for 90 days. The primary outcome of safety was evaluated on days 45 and 90. The secondary outcome of efficacy was evaluated by measuring nutritional status, ALS Functional Rating Scale (ALSFRS) scores, and the occurrence of events such as the initiation of tracheostomy positive pressure ventilation (TPPV) and death. The study included 20 patients (40% female; mean age, 62.0 ± 6.9 years; median disease duration, 1.9 years). Six participants (30%) experienced treatment-emergent adverse events (TEAEs), including elevated creatine kinase levels, liver function test abnormalities, glucose tolerance issues, hyperammonemia, anorexia, dysgeusia, and vasculitis. No serious TEAEs were associated with L-arginine hydrochloride. Over the course of three months, the average changes in body weight, body mass index, and the ALSFRS score were - 0.37 kg, -1.1 kg/m[2], and - 1.7 points, respectively. There were no events requiring TPPV initiation or deaths. This study demonstrated that the oral administration of L-arginine hydrochloride over three months was well tolerated by ALS patients, with no serious TEAEs or deaths attributed to the study drug.Trial Registration number: Japan Registry of Clinical Trials (jRCTs061230001), first registered 11/04/2023.}, } @article {pmid39772789, year = {2025}, author = {Stolwyk, K and Lee, I}, title = {Rapid progression of amyotrophic lateral sclerosis after initiation of GLP-1 agonist: a case report.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {26}, number = {3-4}, pages = {382-384}, pmid = {39772789}, issn = {2167-9223}, support = {K23 NS131586/NS/NINDS NIH HHS/United States ; }, } @article {pmid39771101, year = {2024}, author = {Chetverikova, D and Bakaeva, M and Starikov, S and Kendjieva, A and Chetverikov, S}, title = {The Influence of Plant Growth-Stimulating Bacteria on the Glutathione-S-Transferase Activity and the Toxic Effect of the Herbicide Metsulfuron-Methyl in Wheat and Canola Plants.}, journal = {Toxics}, volume = {12}, number = {12}, pages = {}, pmid = {39771101}, issn = {2305-6304}, support = {23-26-00097//Russian Science Foundation/ ; }, abstract = {The ability of some rhizosphere bacteria to mitigate herbicidal stress in cultivated plants may be useful in agriculture and bioremediation. There is poor understanding of how bacteria directly or through herbicide degradation affect the biochemical processes in plants exposed to sulfonylurea herbicides. In this study, treatment with a combination of herbicide metsulfuron-methyl (MSM) and bacteria (Pseudomonas protegens DA1.2 or P. chlororaphis 4CH) of wheat (Triticum aestivum L.) and canola (Brassica napus L.) plants was carried out. Activity of glutathione-S-transferase (GST), an important enzyme for the herbicide detoxification, and acetolactate synthase (ALS), a target for MSM in plants, was measured by spectrophotometric assays. MSM residues were analyzed using the HPLC-MS. Then, 24 h after bacterial treatment, GST activity increased by 75-91% in wheat and by 38-94% in canola. On the 30th day, a decrease in MSM in the soil associated with bacterial treatment was 54.6-79.7%. An increase in GST activity and acceleration of MSM degradation were accompanied by a decrease in inhibition of the ALS enzyme in plants, which indicated a mitigation of the toxic effect. The results obtained are evidence that rhizospheric bacteria can have beneficial effects on plants exposed to MSM due to the combination of abilities to directly affect detoxification enzymes in plants and degrade MSM in the soil.}, } @article {pmid39770989, year = {2024}, author = {Pekdemir, B and Raposo, A and Saraiva, A and Lima, MJ and Alsharari, ZD and BinMowyna, MN and Karav, S}, title = {Mechanisms and Potential Benefits of Neuroprotective Agents in Neurological Health.}, journal = {Nutrients}, volume = {16}, number = {24}, pages = {}, pmid = {39770989}, issn = {2072-6643}, mesh = {Humans ; *Neuroprotective Agents/pharmacology/therapeutic use ; *Neurodegenerative Diseases/drug therapy ; Brain/drug effects/metabolism ; Animals ; Flavonoids/pharmacology/therapeutic use ; Apoptosis/drug effects ; Antioxidants/pharmacology/therapeutic use ; Oxidative Stress/drug effects ; }, abstract = {The brain contains many interconnected and complex cellular and molecular mechanisms. Injury to the brain causes permanent dysfunctions in these mechanisms. So, it continues to be an area where surgical intervention cannot be performed except for the removal of tumors and the repair of some aneurysms. Some agents that can cross the blood-brain barrier and reach neurons show neuroprotective effects in the brain due to their anti-apoptotic, anti-inflammatory and antioxidant properties. In particular, some agents act by reducing or modulating the accumulation of protein aggregates in neurodegenerative diseases (Alzheimer's disease, Parkinson's disease, Huntington's disease, Amyotrophic lateral sclerosis, and prion disease) caused by protein accumulation. Substrate accumulation causes increased oxidative stress and stimulates the brain's immune cells, microglia, and astrocytes, to secrete proinflammatory cytokines. Long-term or chronic neuroinflammatory response triggers apoptosis. Brain damage is observed with neuronal apoptosis and brain functions are impaired. This situation negatively affects processes such as motor movements, memory, perception, and learning. Neuroprotective agents prevent apoptosis by modulating molecules that play a role in apoptosis. In addition, they can improve impaired brain functions by supporting neuroplasticity and neurogenesis. Due to the important roles that these agents play in central nervous system damage or neurodegenerative diseases, it is important to elucidate many mechanisms. This review provides an overview of the mechanisms of flavonoids, which constitute a large part of the agents with neuroprotective effects, as well as vitamins, neurotransmitters, hormones, amino acids, and their derivatives. It is thought that understanding these mechanisms will enable the development of new therapeutic agents and different treatment strategies.}, } @article {pmid39770252, year = {2024}, author = {Guo, H and Yao, J and Chen, S and Qian, C and Pan, X and Yin, K and Zhu, H and Gao, X and Wang, S and Sun, L}, title = {Enhancing Resistive Switching in AlN-Based Memristors Through Oxidative Al2O3 Layer Formation: A Study on Preparation Techniques and Performance Impact.}, journal = {Micromachines}, volume = {15}, number = {12}, pages = {}, pmid = {39770252}, issn = {2072-666X}, support = {11874105//National Natural Science Foundation of China/ ; }, abstract = {Aluminum nitride (AlN) with a wide band gap (approximately 6.2 eV) has attractive characteristics, including high thermal conductivity, a high dielectric constant, and good insulating properties, which are suitable for the field of resistive random access memory. AlN thin films were deposited on ITO substrate using the radio-frequency magnetron sputtering technique. Al's and Au's top electrodes were deposited on AlN thin films to make a Au/Al/AlN/ITO sandwich structure memristor. The effects of the Al2O3 film on the on/off window and voltage characteristics of the device were investigated. The deposition time and nitrogen content in the sputtering atmosphere were changed to adjust the thickness and composition of AlN films, respectively. The possible mechanism of resistive switching was examined via analyses of the electrical resistive switching characteristics, forming voltage, and switching ratio.}, } @article {pmid39769215, year = {2024}, author = {Wei, Z and Iyer, MR and Zhao, B and Deng, J and Mitchell, CS}, title = {Artificial Intelligence-Assisted Comparative Analysis of the Overlapping Molecular Pathophysiology of Alzheimer's Disease, Amyotrophic Lateral Sclerosis, and Frontotemporal Dementia.}, journal = {International journal of molecular sciences}, volume = {25}, number = {24}, pages = {}, pmid = {39769215}, issn = {1422-0067}, support = {1944247//National Science Foundation/ ; R35GM152245/NH/NIH HHS/United States ; U19-AG056169/NH/NIH HHS/United States ; 253558//Chan Zuckerberg Initiative/ ; }, mesh = {Humans ; *Frontotemporal Dementia/genetics/metabolism/pathology ; *Amyotrophic Lateral Sclerosis/genetics/metabolism/physiopathology ; *Alzheimer Disease/metabolism/genetics/physiopathology/pathology ; *Artificial Intelligence ; Algorithms ; }, abstract = {The overlapping molecular pathophysiology of Alzheimer's Disease (AD), Amyotrophic Lateral Sclerosis (ALS), and Frontotemporal Dementia (FTD) was analyzed using relationships from a knowledge graph of 33+ million biomedical journal articles. The unsupervised learning rank aggregation algorithm from SemNet 2.0 compared the most important amino acid, peptide, and protein (AAPP) nodes connected to AD, ALS, or FTD. FTD shared 99.9% of its nodes with ALS and AD; AD shared 64.2% of its nodes with FTD and ALS; and ALS shared 68.3% of its nodes with AD and FTD. The results were validated and mapped to functional biological processes using supervised human supervision and an external large language model. The overall percentages of mapped intersecting biological processes were as follows: inflammation and immune response, 19%; synapse and neurotransmission, 19%; cell cycle, 15%; protein aggregation, 12%; membrane regulation, 11%; stress response and regulation, 9%; and gene regulation, 4%. Once normalized for node count, biological mappings for cell cycle regulation and stress response were more prominent in the intersection of AD and FTD. Protein aggregation, gene regulation, and energetics were more prominent in the intersection of ALS and FTD. Synapse and neurotransmission, membrane regulation, and inflammation and immune response were greater at the intersection of AD and ALS. Given the extensive molecular pathophysiology overlap, small differences in regulation, genetic, or environmental factors likely shape the underlying expressed disease phenotype. The results help prioritize testable hypotheses for future clinical or experimental research.}, } @article {pmid39769213, year = {2024}, author = {Gu, A and Zhang, Y and He, J and Zhao, M and Ding, L and Liu, W and Xiao, J and Huang, J and Liu, M and Liu, X}, title = {Chronic Oxidative Stress and Stress Granule Formation in UBQLN2 ALS Neurons: Insights into Neuronal Degeneration and Potential Therapeutic Targets.}, journal = {International journal of molecular sciences}, volume = {25}, number = {24}, pages = {}, pmid = {39769213}, issn = {1422-0067}, support = {2016YFC0905100//National Key Research and Development Program of China/ ; 2021JJ30801//Natural Science Foundation of Hunan Province, China/ ; kq2202077//Natural Science Foundation of Changsha, China/ ; 1053320222758//Fundamental Research Funds for the Central Universities of Central South University/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/metabolism/pathology/genetics ; Humans ; *Autophagy-Related Proteins/metabolism/genetics ; *Oxidative Stress ; *Motor Neurons/metabolism/pathology ; Adaptor Proteins, Signal Transducing/metabolism/genetics ; Stress Granules/metabolism ; Induced Pluripotent Stem Cells/metabolism ; Autophagy ; Cell Cycle Proteins/metabolism/genetics ; Nerve Degeneration/pathology/metabolism ; DNA-Binding Proteins/metabolism/genetics ; Sodium Compounds/pharmacology ; }, abstract = {The pathogenesis of neurodegenerative diseases results from the interplay between genetic and environmental factors. Aging and chronic oxidative stress are critical contributors to neurodegeneration. UBQLN2, a ubiquitin-related protein, aids in protein degradation and protects against oxidative stress. In ALS neurons harboring UBQLN2 mutations, oxidative stress accelerates pathological changes, yet the precise mechanisms remain unclear. Using induced motor neurons (iMNs) derived from UBQLN2 P497H iPSCs, we observed ALS-like phenotypes, including TDP-43 mislocalization, increased cell death, and reduced viability. Sodium arsenite (SA)-induced oxidative stress triggered stress granule formation, while autophagy dysfunction exacerbated neuronal degeneration. CHX and bosutinib treatments reduced ubiquitinated protein accumulation and alleviated degeneration, highlighting potential therapeutic pathways. These findings emphasize the role of chronic oxidative stress and stress granule formation in UBQLN2 ALS, offering insights into novel therapeutic targets.}, } @article {pmid39769209, year = {2024}, author = {Xing, C and Chen, H and Bi, W and Lei, T and Hang, Z and Du, H}, title = {Targeting 5-HT Is a Potential Therapeutic Strategy for Neurodegenerative Diseases.}, journal = {International journal of molecular sciences}, volume = {25}, number = {24}, pages = {}, pmid = {39769209}, issn = {1422-0067}, support = {32300682//National Natural Science Foundation of China/ ; }, mesh = {Humans ; *Serotonin/metabolism ; *Neurodegenerative Diseases/metabolism/drug therapy ; Animals ; Alzheimer Disease/metabolism/drug therapy ; Amyotrophic Lateral Sclerosis/metabolism/drug therapy ; Parkinson Disease/metabolism/drug therapy ; Receptors, Serotonin/metabolism ; }, abstract = {There is increasing interest in the potential therapeutic role of 5-HT (serotonin) in the treatment of neurodegenerative diseases, which are characterized by the progressive degeneration and death of nerve cells. 5-HT is a vital neurotransmitter that plays a central role in regulating mood, cognition, and various physiological processes in the body. Disruptions in the 5-HT system have been linked to several neurological and psychiatric disorders, making it an attractive target for therapeutic intervention. Although the exact causes of neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS) are not fully understood, researchers believe that regulating the 5-HT system could help alleviate symptoms and potentially slow the progression of these diseases. Here, we delve into the potential of harnessing 5-HT as a therapeutic target for the treatment of neurodegenerative diseases. It is important to note that the current clinical drugs targeting 5-HT are still limited in the treatment of these complex diseases. Therefore, further research and clinical trials are needed to evaluate the feasibility and effectiveness of its clinical application.}, } @article {pmid39769187, year = {2024}, author = {O'Day, DH}, title = {The Search for a Universal Treatment for Defined and Mixed Pathology Neurodegenerative Diseases.}, journal = {International journal of molecular sciences}, volume = {25}, number = {24}, pages = {}, pmid = {39769187}, issn = {1422-0067}, mesh = {Animals ; Humans ; alpha-Synuclein/metabolism ; Alzheimer Disease/metabolism/pathology/drug therapy/therapy ; Amyloid beta-Peptides/metabolism ; Biomarkers/metabolism ; Calmodulin/metabolism ; *Neurodegenerative Diseases/metabolism/pathology/therapy ; Parkinson Disease/metabolism/pathology/therapy ; Protein Glutamine gamma Glutamyltransferase 2 ; RNA-Binding Protein FUS/metabolism/genetics ; tau Proteins/metabolism ; Transglutaminases/metabolism ; }, abstract = {The predominant neurodegenerative diseases, Alzheimer's disease, Parkinson's disease, dementia with Lewy Bodies, Huntington's disease, amyotrophic lateral sclerosis, and frontotemporal dementia, are rarely pure diseases but, instead, show a diversity of mixed pathologies. At some level, all of them share a combination of one or more different toxic biomarker proteins: amyloid beta (Aβ), phosphorylated Tau (pTau), alpha-synuclein (αSyn), mutant huntingtin (mHtt), fused in sarcoma, superoxide dismutase 1, and TAR DNA-binding protein 43. These toxic proteins share some common attributes, making them potentially universal and simultaneous targets for therapeutic intervention. First, they all form toxic aggregates prior to taking on their final forms as contributors to plaques, neurofibrillary tangles, Lewy bodies, and other protein deposits. Second, the primary enzyme that directs their aggregation is transglutaminase 2 (TGM2), a brain-localized enzyme involved in neurodegeneration. Third, TGM2 binds to calmodulin, a regulatory event that can increase the activity of this enzyme threefold. Fourth, the most common mixed pathology toxic biomarkers (Aβ, pTau, αSyn, nHtt) also bind calmodulin, which can affect their ability to aggregate. This review examines the potential therapeutic routes opened up by this knowledge. The end goal reveals multiple opportunities that are immediately available for universal therapeutic treatment of the most devastating neurodegenerative diseases facing humankind.}, } @article {pmid39768371, year = {2024}, author = {Orlova, A and Malygin, Y and Gofman, A and Sotulenko, S and Gandalian, V and Kartashov, I and Brylev, L and Bolevich, S and Nikolic Turnic, T and Jakovljevic, V}, title = {Survival Prognostic Factors of Non-Invasive Ventilation in Amyotrophic Lateral Sclerosis: A Systematic Review.}, journal = {Life (Basel, Switzerland)}, volume = {14}, number = {12}, pages = {}, pmid = {39768371}, issn = {2075-1729}, abstract = {OBJECTIVE: Amyotrophic lateral sclerosis is a neurodegenerative disease with high rates of disability and mortality. Non-invasive ventilation (NIV) is an effective method of treating patients, increasing life expectancy, but currently, predictors available to determine the best outcome of therapy in this category of patients are unknown. This systematic review aimed to determine the impact of prognostic factors on benefits from NIV application compared with non-NIV tools of treatment (invasive ventilation and standard care) in case of survival of ALS patients.

METHOD: We systematically sought relevant longitudinal cohort and case-control studies published in PubMed, CINAHL/EMBASE, Cochrane library, and Scopus.

RESULTS: We included seven prospective studies, published in 2010-2020, in the analysis. According to the evidence base available to date, NIV favors survival compared to non-NIV in patients with bulbar onset ALS. We obtained conflicting data on the significance of spinal onset and bulbar function. Survival depending on patient age, and also for spinal, cervical, and flail limb phenotypes during NIV therapy has not been sufficiently studied and needs further investigation.

CONCLUSIONS: The studies analyzed in this review allow us to state with confidence that NIV is effective in bulbar onset ALS, taking into account recommendations for duration of ventilation and the use of the full range of symptomatic therapy, including mechanically assisted coughing. The effectiveness of NIV on severe bulbar symptoms requires further research.}, } @article {pmid39768167, year = {2024}, author = {Chen, X and Lv, S and Liu, J and Guan, Y and Xu, C and Ma, X and Li, M and Bai, X and Liu, K and Zhang, H and Yan, Q and Zhou, F and Chen, Y}, title = {Exploring the Role of Axons in ALS from Multiple Perspectives.}, journal = {Cells}, volume = {13}, number = {24}, pages = {}, pmid = {39768167}, issn = {2073-4409}, support = {82271483//The National Natural Science Foundation of China/ ; ZR2024MH112; ZR2024QH628//Shandong Province Natural Science Foundation of China/ ; 2023YX036; 2022YX043//Weifang Science and Technology Development Plan Project/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/pathology ; *Axons/pathology/metabolism ; Animals ; Axonal Transport ; Motor Neurons/pathology ; Disease Progression ; }, abstract = {Amyotrophic lateral sclerosis (ALS), commonly known as motor neuron disease, is a neurodegenerative disorder characterized by the progressive degeneration of both upper and lower motor neurons. This pathological process results in muscle weakness and can culminate in paralysis. To date, the precise etiology of ALS remains unclear. However, a burgeoning body of research indicates that axonal dysfunction is a pivotal element in the pathogenesis of ALS and significantly influences the progression of disease. Dysfunction of axons in ALS can result in impediments to nerve impulse transmission, leading to motor impairment, muscle atrophy, and other associated complications that severely compromise patients' quality of life and survival prognosis. In this review, we concentrate on several key areas: the ultrastructure of axons, the mechanisms of axonal degeneration in ALS, the impact of impaired axonal transport on disease progression in ALS, and the potential for axonal regeneration within the central nervous system (CNS). Our objective is to achieve a more holistic and profound understanding of the multifaceted role that axons play in ALS, thereby offering a more intricate and refined perspective on targeted axonal therapeutic interventions.}, } @article {pmid39767639, year = {2024}, author = {Wan, M and Zhang, L and Huo, J and Fu, Y and Huang, T and Fan, D}, title = {Genetic Variation in Targets of Antidiabetic Drugs and Amyotrophic Lateral Sclerosis Risk.}, journal = {Biomedicines}, volume = {12}, number = {12}, pages = {}, pmid = {39767639}, issn = {2227-9059}, support = {82101490, and 82071426//National Natural Science Foundation of China/ ; }, abstract = {BACKGROUND: Previous studies have suggested that antidiabetic drug use may be associated with amyotrophic lateral sclerosis. However, these studies are limited by many confounding and reverse causality biases. We aimed to determine whether antidiabetic drug use has causal effects on ALS.

METHODS: Drug-target Mendelian randomization analysis was conducted to evaluate the association between genetic variation in the targets of antidiabetic drugs and ALS risk. The antidiabetic drugs included sulfonylureas, GLP-1 analogues, thiazolidinediones, insulin/insulin analogues, metformin, and SGLT2 inhibitors. Summary statistics for ALS were retrieved from previous genome-wide association studies comprising 27,205 ALS patients and 55,058 controls. The instrumental variables for these drugs are from previous published articles.

RESULTS: Genetic variation in SGLT2 inhibition targets was associated with lower risk of ALS (odds ratio [OR] = 0.32, 95% CI = 0.14-0.74; p = 0.008). We did not find that genetic variation in metformin targets was associated with ALS (OR = 1.61, 95% CI = 0.94-2.73; p = 0.081). Nevertheless, mitochondrial complex I, a target of metformin, was associated with a higher risk of ALS (OR = 1.83, 95% CI = 1.01-3.32; p = 0.047). The analysis showed that genetic variation in sulfonylureas, GLP-1 analogues, thiazolidinediones, insulin or insulin analogues targets was not associated with ALS (all p > 0.05).

CONCLUSIONS: The complex interaction between hypoglycemic, antioxidation, and anti-inflammatory effects may account for the different results across antidiabetic drug types. These findings provide key evidence to guide the use of antidiabetic drugs and will help to identify novel therapeutic targets in ALS.}, } @article {pmid39766833, year = {2024}, author = {Bisogni, G and Conte, A and Costantino, U and Lattante, S and Bernardo, D and Lucioli, G and Patanella, AK and Cimbolli, P and Del Giudice, E and Vettor, F and Marangi, G and Doronzio, PN and Zollino, M and Sabatelli, M}, title = {Exploring the Role of CCNF Variants in Italian ALS Patients.}, journal = {Genes}, volume = {15}, number = {12}, pages = {}, pmid = {39766833}, issn = {2073-4425}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics ; Male ; Female ; Italy ; Middle Aged ; Aged ; Mutation, Missense ; Cyclins/genetics ; Frontotemporal Dementia/genetics/pathology ; Genetic Association Studies ; High-Throughput Nucleotide Sequencing ; Phenotype ; Adult ; Genetic Predisposition to Disease ; }, abstract = {Objectives: Variants in Cyclin F (CCNF) have been associated to amyotrophic lateral sclerosis (ALS) and/or frontotemporal dementia (FTD) in a group of cases. The objectives of this study were to determine the contribution of CCNF in a large cohort of Italian ALS patients, to look for genotype-phenotype correlation of the mutations and to evaluate the CCNF-associated clinical features. Methods: We applied next-generation sequencing technologies on 971 unrelated Italian ALS patients and we filtered results to look for variants in CCNF gene. Results: We identified 13 rare missense variants in 16 index cases (2 familial and 14 sporadic), with a cumulative mutational frequency of 1.6%. The most prevalent variant was p.Phe197Leu, found in three patients. The clinical presentation was heterogeneous, with a classic phenotype in eight patients, upper motor neuron dominant (UMN-D) phenotype in four patients, and flail arm in four patients. Clinical evaluation for cognitive impairment was performed in 13 patients using the Edinburgh Cognitive and Behavioural ALS Screen (ECAS) test, demonstrating that almost half of the patients (n = 6) had variable degrees of frontal dysfunction. Discussion: In our cohort, we observed CCNF variants in 1.6% of patients (16/971), a percentage similar to that found in other series. Clinical presentation is heterogeneous, but CCNF variants are significantly associated to cognitive impairment. Conclusions: Our study expands the CCNF genetic variant spectrum in a large cohort of Italian ALS patients. Further studies are needed to assess genotype-phenotype associations of CCNF variants and to specify the role of each variant, which are quite common, especially in sALS patients.}, } @article {pmid39766450, year = {2024}, author = {Donaghy, R and Pioro, EP}, title = {Neurophysiologic Innovations in ALS: Enhancing Diagnosis, Monitoring, and Treatment Evaluation.}, journal = {Brain sciences}, volume = {14}, number = {12}, pages = {}, pmid = {39766450}, issn = {2076-3425}, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive disease of both upper motor neurons (UMNs) and lower motor neurons (LMNs) leading invariably to decline in motor function. The clinical exam is foundational to the diagnosis of the disease, and ordinal severity scales are used to track its progression. However, the lack of objective biomarkers of disease classification and progression delay clinical trial enrollment, muddle inclusion criteria, and limit accurate assessment of drug efficacy. Ultimately, biomarker evidence of therapeutic target engagement will support, and perhaps supplant, more traditional clinical trial outcome measures. Electrophysiology tools including nerve conduction study and electromyography (EMG) have already been established as diagnostic biomarkers of LMN degeneration in ALS. Additional understanding of the motor manifestations of disease is provided by motor unit number estimation, electrical impedance myography, and single-fiber EMG techniques. Dysfunction of UMN and non-motor brain areas is being increasingly assessed with transcranial magnetic stimulation, high-density electroencephalography, and magnetoencephalography; less common autonomic and sensory nervous system dysfunction in ALS can also be characterized. Although most of these techniques are used to explore the underlying disease mechanisms of ALS in research settings, they have the potential on a broader scale to noninvasively identify disease subtypes, predict progression rates, and assess physiologic engagement of experimental therapies.}, } @article {pmid39766276, year = {2024}, author = {Wysoczański, B and Świątek, M and Wójcik-Gładysz, A}, title = {Organ-on-a-Chip Models-New Possibilities in Experimental Science and Disease Modeling.}, journal = {Biomolecules}, volume = {14}, number = {12}, pages = {}, pmid = {39766276}, issn = {2218-273X}, mesh = {*Lab-On-A-Chip Devices ; Humans ; Animals ; Models, Biological ; Liver/metabolism/cytology ; Cell Culture Techniques/methods ; Microphysiological Systems ; }, abstract = {'Organ-on-a-chip' technology is a promising and rapidly evolving model in biological research. This innovative microfluidic cell culture device was created using a microchip with continuously perfused chambers, populated by living cells arranged to replicate physiological processes at the tissue and organ levels. By consolidating multicellular structures, tissue-tissue interfaces, and physicochemical microenvironments, these microchips can replicate key organ functions. They also enable the high-resolution, real-time imaging and analysis of the biochemical, genetic, and metabolic activities of living cells in the functional tissue and organ contexts. This technology can accelerate research into tissue development, organ physiology and disease etiology, therapeutic approaches, and drug testing. It enables the replication of entire organ functions (e.g., liver-on-a-chip, hypothalamus-pituitary-on-a-chip) or the creation of disease models (e.g., amyotrophic lateral sclerosis-on-a-chip, Parkinson's disease-on-a-chip) using specialized microchips and combining them into an integrated functional system. This technology allows for a significant reduction in the number of animals used in experiments, high reproducibility of results, and the possibility of simultaneous use of multiple cell types in a single model. However, its application requires specialized equipment, advanced expertise, and currently incurs high costs. Additionally, achieving the level of standardization needed for commercialization remains a challenge at this stage of development.}, } @article {pmid39765493, year = {2024}, author = {Zhang, T and Xu, Q and Zhou, B and Xiao, J and Zheng, S and Li, J and Lv, Q and Zhang, Y and Wang, R and Su, R and Wang, Z}, title = {Development and Validation of a 5K Liquid Chip for Identifying Cashmere Goat Populations in Inner Mongolia Autonomous Region.}, journal = {Animals : an open access journal from MDPI}, volume = {14}, number = {24}, pages = {}, pmid = {39765493}, issn = {2076-2615}, support = {2022YFE0113300，2022YFD1300201,2022YFD1300204//National Key Research and Development Program/ ; BR220112//Project for Enhancing Young Teacher's Research Ability/ ; NJYT22038//Program for Young Talents of Science and Technology in Universities of Inner Mongolia Autonomous Region/ ; 2023ZD0405102//Project for 2030 Science and Technology Innovation Major/ ; NMGIRT2322//Program for Inner Mongolia Autonomous Region Higher Education Innovation Team Development/ ; }, abstract = {(1) Background: Cashmere goats, as one of the characteristic species, are rich in genetic resources. Protecting and rationally utilizing these genetic resources is of great significance for the genetic improvement of cashmere goats. (2) Methods: In this study, tissue samples were collected from Inner Mongolia white cashmere goats, which included the Arbas type (ARBS); Erlangshan type (ELS); Alashan type (ALS), Hanshan white cashmere goats (HS), and Ujimqin white cashmere goats (WZMQ). Genomic DNA was extracted and subjected to high-depth genome resequencing. GenoBait technology was used for probe design and site optimization, followed by the synthesis of a low-density liquid phase chip. Finally, a total of 281 individuals from five cashmere goat populations in the Inner Mongolia Autonomous Region were randomly selected to verify the chip. (3) Results: The results showed that a total of 5002 SNP sites were finally screened and retained for the synthesis of the low-density liquid chip for identifying cashmere goats in Inner Mongolia Autonomous Region. Principal component analysis and phylogenetic tree construction indicated that the ARBS, ELS, and ALS populations were clustered into one category. (4) Conclusions: This chip can accurately identify the three breeds: Inner Mongolia white cashmere goats, Hanshan white cashmere goats, and Ujimqin white cashmere goats.}, } @article {pmid39764140, year = {2024}, author = {Akif, A and My Nguyen, TT and Liu, L and Xu, X and Kulkarni, A and Jiang, J and Zhang, Y and Hao, J}, title = {Targeting NLRP3 signaling with a novel sulfonylurea compound for the treatment of vascular cognitive impairment and dementia.}, journal = {Research square}, volume = {}, number = {}, pages = {}, pmid = {39764140}, issn = {2693-5015}, support = {R01 NS105787/NS/NINDS NIH HHS/United States ; R21 NS133895/NS/NINDS NIH HHS/United States ; }, abstract = {BACKGROUND: As a key inflammatory factor, the nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 (NLRP3) inflammasome plays a crucial role in neuroinflammation and the progression of neurodegenerative diseases. Dysregulation of NLRP3 signaling can trigger various inflammatory responses in the brain, contributing to the development of neurodegenerative diseases such as ischemic stroke, vascular dementia (VaD), Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). Therefore, the NLRP3 signaling pathway is a promising therapeutic target for the treatment of neurodegenerative diseases, including VaD.

METHODS: In this study, we investigated the therapeutic effects of a synthetic sulfonylurea NLRP3 inhibitor, AMS-17, in a VaD mouse model using bilateral common carotid artery stenosis (BCAS) and elucidated the underlying mechanisms. All mice were randomly divided into three groups: Sham, VaD + Vehicle, and VaD + AMS-17. Cognitive function was assessed using the Y-maze and Morris water maze (MWM) on the 50[th] day after BCAS. Brain sections and blood serum samples were collected for biomarker analysis and immunohistochemistry. Neurodegeneration, expressions of the molecules involved in the NLRP3 signaling pathways, tight junction proteins, and myelination were assessed using western blotting and immunofluorescence (IF). The levels of Interleukin-1 beta (IL-1β), Tumor Necrosis Factor-alpha (TNF-α) and Interleukin-4 (IL-4) in the blood were measured using ELISA.

RESULTS: AMS-17 treatment improved cognitive function, enhanced blood-brain barrier (BBB) integrity, and promoted remyelination in VaD mice. Additionally, AMS-17 reduced neurodegeneration and decreased the expression of NLRP3 and its associated proteins, Apoptosis-associated speck-like protein (ASC), and cleaved caspase-1 in the brain. It also lowered pro-inflammatory TNF-α and IL-1β levels, while increasing the anti-inflammatory IL-4 level in the blood.

CONCLUSIONS: The findings of this study provide the first promising evidence for the use of AMS-17 in VaD treatment in mice. This study introduces AMS-17 as a novel chemical scaffold with NLRP3 inhibitory activity, which can be further developed for the treatment of VaD in humans.}, } @article {pmid39763885, year = {2024}, author = {Shelest, O and Tindel, I and Lauzon, M and Dawson, A and Ho, R}, title = {Delineating sex-dependent and anatomic decline of motor functions in the SOD1G93A mouse model of amyotrophic lateral sclerosis.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {39763885}, issn = {2692-8205}, support = {R00 AG056678/AG/NIA NIH HHS/United States ; }, abstract = {The transgenic SOD1G93A mouse model is the most widely used animal model of amyotrophic lateral sclerosis (ALS), a fatal disease of motor neuron degeneration. While genetic background influences onset and progression variability of motor dysfunction, the C57BL/6 background most reliably exhibits robust ALS phenotypes; thus, it is the most widely used strain in mechanistic studies. In this model, paresis begins in the hindlimbs and spreads rostrally to the forelimbs. Males experience earlier onset, greater disease severity, and shorter survival than females. However, the influence of sex on patterns of declining motor function between forelimbs and hindlimbs as well as among distinct, spinal-innervated muscle groups within each limb are not fully understood. To provide a higher resolution framework of degenerating motor function across the body, we conducted more comprehensive, limb-dependent and independent measures of motor decline over the course of disease. Subsequently, we compared the timing and intensity of these features across sex, and we consider to what extent these patterns are conserved in clinical observations from human ALS patients. We found male mice experienced earlier and less localized onset than females. We also report distinct motor features decline at different rates between sexes. Finally, mice showed differences in correlation between the decline of left- and right-side measures of the hindlimb. Consequently, our findings reinforce and refine the utility of the SOD1 mouse in modeling more highly resolved, sex-specific differences in ALS patient motor behavior. This may better guide preclinical studies in stratifying patients by sex and anatomical site of onset.}, } @article {pmid39762986, year = {2025}, author = {Berlowitz, DJ and Rowe, D and Howard, ME and Piper, A and Graco, M and Braat, S and Singh, B and Souza, TV and Lannin, N and McLean, A and Sawyer, A and Carey, KA and Ahamed, Y and , }, title = {Polysomnographic titration of non-invasive ventilation in motor neurone disease (3TLA): study protocol for a randomised controlled trial.}, journal = {Trials}, volume = {26}, number = {1}, pages = {10}, pmid = {39762986}, issn = {1745-6215}, mesh = {Humans ; *Noninvasive Ventilation/methods/adverse effects/instrumentation ; *Motor Neuron Disease/therapy/physiopathology ; *Polysomnography ; *Randomized Controlled Trials as Topic ; Treatment Outcome ; Australia ; Multicenter Studies as Topic ; Time Factors ; Sleep ; Respiratory Insufficiency/therapy/physiopathology ; Quality of Life ; }, abstract = {BACKGROUND: Non-invasive ventilation (NIV) uses positive pressure to assist people with respiratory muscle weakness or severe respiratory compromise to breathe. Most people use this treatment during sleep when breathing is most susceptible to instability. The benefits of using NIV in motor neurone disease (MND) are well-established. However, uptake and usage are low (~ 19%) and there is no consensus on how to best implement NIV in MND in Australia. Consequently, clinical practice models are highly variable. Our team has recently provided evidence that specific and individualised NIV titration using a sleep study (polysomnography; PSG) leads to better outcomes in people with MND. However, for this clinical practice model to result in sustained benefits, evidence of effectiveness across multiple sites, as well as culture and practice change, must occur.

METHODS: A two-arm, assessor-blinded, individual participant randomised controlled trial in MND care centres across Australia will be undertaken. Two-hundred and forty-four participants will be randomised (1:1) to either the intervention group (PSG-assisted commencement of NIV settings; PSG) or a control group (sham PSG). Participants will be asked to use their NIV device for 7 weeks and will then return for follow-up assessments. Respiratory, sleep and patient-reported outcome measures will be collected at baseline and follow-up. The primary aim is to determine if the proportion of participants using NIV for > 4 h/day during the intervention period is higher in the PSG than the control group. A process evaluation, health economic evaluation and 12-month cohort follow-up will be undertaken and reported separately.

DISCUSSION: The results of this trial will demonstrate the effects of PSG-assisted titration of NIV on usage of NIV in people with MND. We hypothesise that the PSG intervention will improve synchrony between the user and the machine, which will lead to greater NIV usage compared to the control group.

TRIAL REGISTRATION: ClinicalTrials.gov NCT05136222. Registered on November 25, 2021.}, } @article {pmid39762711, year = {2025}, author = {Apostolo, D and Ferreira, LL and D'Onghia, D and Vincenzi, F and Vercellino, N and Perazzi, M and Pirisi, M and Cantello, R and Minisini, R and Mazzini, L and Bellan, M and De Marchi, F}, title = {Lower Circulating Gas6 Levels Are Associated with Bulbar Phenotype and Faster Disease Progression in Amyotrophic Lateral Sclerosis Patients.}, journal = {Molecular neurobiology}, volume = {62}, number = {5}, pages = {6273-6282}, pmid = {39762711}, issn = {1559-1182}, support = {2021-1541//Fondazione Cariplo/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/blood/pathology ; *Disease Progression ; Male ; Female ; Middle Aged ; Phenotype ; *Intercellular Signaling Peptides and Proteins/blood ; Aged ; Biomarkers/blood ; Prospective Studies ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder that primarily affects the motor neurons in the brain and spinal cord. While the exact cause of ALS is not fully understood, a combination of genetic and environmental factors is believed to contribute to its development. Growth arrest-specific 6 (Gas6), a vitamin K-dependent protein, has been recognized to enhance oligodendrocytes and neurons' survival and is associated with different kinds of (neuro)inflammatory conditions. Therefore, we aimed to determine a possible implication of Gas6 in ALS phenotype and progression by evaluating the value of circulating Gas6 and its soluble receptors (sAxl, sMer, sTyro-3) in ALS patients. We conducted a prospective observational study including 65 ALS patients and measured the circulating serum levels of Gas6, sAxl, sMer, soluble Tyro-3 (sTyro-3), and neurofilaments (NfLs). In our ALS cohort, lower serum levels of Gas6 and concomitantly higher levels of NfLs were associated with a more aggressive disease, expressed with bulbar phenotype (p-value for Gas6 = 0.03) and faster progression (p-value for Gas6 = 0.03). Also, serum Gas6 was able to distinguish (area under the curve, cut-off 13.70 ng/mL, sensitivity 69.57%, specificity 72.72%) between fast and slow progressors. Due to its neuroprotective properties, our data suggest that Gas6 could be an intriguing biomarker in ALS patients.}, } @article {pmid39761853, year = {2025}, author = {Weeks, AT and Bird, AJ}, title = {Regulation of sod1 mRNA and protein abundance by zinc in fission yeast is dependent on the CCR4-NOT complex.}, journal = {The Journal of biological chemistry}, volume = {301}, number = {2}, pages = {108156}, pmid = {39761853}, issn = {1083-351X}, support = {R01 GM105695/GM/NIGMS NIH HHS/United States ; }, mesh = {*Schizosaccharomyces/genetics/metabolism/enzymology ; *Schizosaccharomyces pombe Proteins/metabolism/genetics ; *Zinc/metabolism/pharmacology ; *RNA, Messenger/genetics/metabolism/biosynthesis ; Superoxide Dismutase-1 ; *Gene Expression Regulation, Fungal/drug effects ; *Superoxide Dismutase/genetics/metabolism/biosynthesis ; *Ribonucleases/metabolism/genetics ; }, abstract = {Zinc is an essential micronutrient that serves as a cofactor in a wide variety of enzymes, including Cu-Zn Superoxide Dismutase 1 (Sod1). We have discovered in Schizosaccharomyces pombe that Sod1 mRNA and protein levels are regulated in response to cellular zinc availability. We demonstrate that lower levels of sod1 mRNA and protein accumulate under low zinc conditions and that this regulation does not require the sod1 promoter or known factors that regulate the transcription of sod1 in response to zinc and other environmental stresses. Further analyses using yeast deletion strains and an inactive allele of Caf1 revealed that the reduced accumulation of sod1 mRNA and protein under low zinc conditions depends on the Caf1 and Ccr4 deadenylases of the CCR4-NOT complex. We also found that Caf1 and Ccr4 are both required for growth under zinc-limiting conditions. To gain additional mechanistic insight we used immunoblot analysis to map the regions required for the regulation of the Sod1 protein by zinc. We found that the sod1 ORF and 3'UTR are both necessary and sufficient for the zinc-dependent changes in Sod1 protein abundance. Our studies reveal a novel mechanism of altering mRNA and protein abundance in response to zinc status, which depends on the CCR4-NOT complex.}, } @article {pmid39759580, year = {2025}, author = {Chourpiliadis, C and Lovik, A and Seitz, C and Hu, Y and Wu, J and Ljungman, P and Press, R and Samuelsson, K and Ingre, C and Fang, F}, title = {Association between cardiometabolic diseases and the risk and progression of motor neuron diseases in Sweden: a population-based case-control study.}, journal = {The Lancet regional health. Europe}, volume = {49}, number = {}, pages = {101173}, pmid = {39759580}, issn = {2666-7762}, abstract = {BACKGROUND: The evidence on the link between cardiometabolic diseases (CMDs) and motor neuron diseases (MNDs) remains inconsistent. We aimed to determine whether there is an association of CMDs, namely, any cardiovascular disease, cardiac arrhythmia, heart failure, thromboembolic disease, hypertension, cerebrovascular disease, ischemic heart disease, diabetes mellitus type 2, and hypercholesterolemia with the risk and progression of MNDs.

METHODS: We included 1463 MND patients (amyotrophic lateral sclerosis (ALS), primary lateral sclerosis (PLS), progressive spinal muscular atrophy (PSMA), and unspecified MND) diagnosed from January 1, 2015, to July 1, 2023, in Sweden according to the Swedish Motor Neuron Disease Quality Registry (i.e., cases), up to 5 MND-free population controls per case (N = 7311) who were individually matched to the cases on age and sex, and the full siblings (N = 2002) and spouses (N = 1220) of MND patients (i.e., relative controls). Conditional logistic regression models were used to estimate the risk of MND diagnosis in relation to previous CMDs, through comparing MND patients to population controls or relative controls. MND patients were followed from diagnosis to assess the role of pre-diagnostic CMDs on disease progression. A joint longitudinal-survival model was used to estimate risk of mortality (or use of invasive ventilation) in relation to CMDs after taking into account the longitudinal changes of ALS functional rating scale-revised (ALSFRS-R) in the time-to-event analysis. Hierarchical clustering with the Ward's linkage and a dissimilarity matrix created by Gower's method was used to identify clusters of MND patients with distinct phenotypes.

FINDINGS: Among the CMDs studied, a history of diabetes mellitus type 2 (OR 0.75; 95% CI 0.62, 0.93) or hypercholesterolemia (OR 0.82; 95% CI 0.71, 0.94) more than one year before diagnosis was associated with a lower risk for MNDs. The associations persisted for more than five years before MND diagnosis. MND patients with a history of any cardiovascular disease (HR 1.43; 95% CI 1.13, 1.81), arrhythmia (HR 1.42; 95% CI 1.04, 1.93), heart failure (HR 1.79; 95% CI 1.02, 3.14), hypertension (HR 1.41; 95% CI 1.12, 1.77), or hypercholesterolemia (HR 1.28; 95% CI 1.01, 1.62) had an increased mortality risk, compared to others, after taking into consideration the longitudinal changes in ALSFRS-R. Cluster analysis identified two clusters of MND patients, where one cluster demonstrated higher age, worse functional status, and higher prevalence of CMDs at the time of diagnosis as well as a higher mortality and faster functional decline during follow-up, compared to the ones included in the other cluster.

INTERPRETATION: Diabetes mellitus type 2 and hypercholesterolemia were associated with a lower future risk of MND. On the other hand, most of the CMDs were indicative of a poor disease progression after an MND diagnosis.

FUNDING: European Research Council, US Center for Disease Control and Prevention, Swedish Research Council.}, } @article {pmid39759457, year = {2024}, author = {Ahmad, SR and Zeyaullah, M and Khan, MS and AlShahrani, AM and Altijani, AAG and Ali, H and Dawria, A and Mohieldin, A and Alam, MS and Mohamed, AOA}, title = {Pharmacogenomics for neurodegenerative disorders - a focused review.}, journal = {Frontiers in pharmacology}, volume = {15}, number = {}, pages = {1478964}, pmid = {39759457}, issn = {1663-9812}, abstract = {Neurodegenerative disorders such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS) are characterized by the progressive degeneration of neuronal structure and function, leading to severe cognitive and motor impairments. These conditions present significant challenges to healthcare systems, and traditional treatments often fail to account for genetic variability among patients, resulting in inconsistent therapeutic outcomes. Pharmacogenomics aims to tailor medical treatments based on an individual's genetic profile, thereby improving therapeutic efficacy and reducing adverse effects. This focused review explores the genetic factors influencing drug responses in neurodegenerative diseases and the potential of pharmacogenomics to revolutionize their treatment. Key genetic markers, such as the APOE ε4 allele in AD and the CYP2D6 polymorphisms in PD, are highlighted for their roles in modulating drug efficacy. Additionally, advancements in pharmacogenomic tools, including genome-wide association studies (GWAS), next-generation sequencing (NGS), and CRISPR-Cas9, are discussed for their contributions to personalized medicine. The application of pharmacogenomics in clinical practice and its prospects, including ethical and data integration challenges, are also examined.}, } @article {pmid39757610, year = {2024}, author = {Mojgani, N and Dadar, M and Shahali, Y and Simal-Gandara, J and Kumar, P and Ashique, S and Bhowmick, M and Kumar, H}, title = {Antioxidant Nutraceuticals: Their Adjunct Role in the Management of COVID-19 Infections and Post-COVID Syndrome.}, journal = {Infectious disorders drug targets}, volume = {}, number = {}, pages = {}, doi = {10.2174/0118715265320091241017161919}, pmid = {39757610}, issn = {2212-3989}, abstract = {The COVID-19 epidemic in recent years has been produced by various coronavirus strains that nearly destroyed world health policies and economics. Emerging viral strains exac-erbated the pandemic. Huge investments have been made in preventative vaccines to combat the disease, but the genetic instability of these viruses has hampered their usefulness. However, in addition to traditional therapeutic approaches, nutraceuticals have been considered effica-cious in preventing and or treating COVID-19 and post-COVID syndrome. In this context, nutraceuticals such as vitamins or dietary supplements including multiple vitamins and miner-als and propolis have been widely studied for their significant impact on viral respiratory dis-eases like SARS-CoV-2 and COVID-19. Some of these nutraceuticals having antioxidant, anti-inflammatory, and immune-modulatory properties have been highly recommended for use as an adjunct option to moderate the adverse effects associated with the COVID-19 pandemic. In this review, we intend to present the recent understanding and converse scientific implications for the use of nutraceutical antioxidants such as vitamins, minerals, probiotics, and polyphenols like bee propolis, in the management of viral respiratory diseases and post-COVID-19 syn-drome. Future challenges and limitations regarding the use and bioavailability of these ingre-dients, and dose-response studies are further emphasized.}, } @article {pmid39756374, year = {2025}, author = {Loap, P and Kirova, Y}, title = {Initial Characterization and Outcome Assessment of Anal Lymphomas in a Large-Size Contemporary Cohort: A Population-Based SEER Database Study (2000-2022).}, journal = {Acta haematologica}, volume = {}, number = {}, pages = {1-7}, doi = {10.1159/000541595}, pmid = {39756374}, issn = {1421-9662}, abstract = {INTRODUCTION: Anal lymphoma (AL) is a rare presentation of extranodal lymphomas, characterized by occurrence in the anal area and largely understudied due to its infrequency. This study aimed to address gaps in knowledge about AL's demographic and clinical profiles, treatments, and survival outcomes, leveraging data from the SEER program.

METHODS: We conducted a retrospective analysis of 79 AL cases identified in the SEER database from 2000 to 2022; 36 stage I AL cases were identified and defined as localized primary anal lymphoma (L-PAL). Data on demographics, tumor specifics, treatment modalities, and survival were analyzed using the Kaplan-Meier method and Cox proportional hazards models.

RESULTS: The majority of AL cases were diffuse large B-cell lymphoma (70.9%). Other notable subtypes included anaplastic T-cell lymphoma, marginal zone lymphoma, B-cell non-Hodgkin lymphoma, Burkitt lymphoma/leukemia (each accounting for 6.3%), followed by follicular lymphoma and mantle-cell lymphoma (each at 1.3%). AL primarily affected younger males (median age 50), with a significant majority being Caucasian. Initial stages (I and II) were more commonly observed, and treatments varied, with chemotherapy being most prevalent (67.1%), followed by radiation (30.4%) and surgery (30.4%). The 5- and 10-year overall survival (OS) rates were 59.4% and 44.1%, respectively, while the corresponding cancer-specific survival (CSS) rates were 67.9% and 58.0%, respectively. Age was a significant prognostic factor for OS but not for CSS. Radiotherapy tended to improve CSS in the AL population.

CONCLUSION: This research corresponds to the first in-depth analysis of AL, highlighting its distinct demographic patterns, clinical features, and responses to various treatments, distinguishing it from other types of anal cancers. Our results underscore the importance of developing specialized diagnostic and treatment strategies. To enhance our understanding and management of this uncommon form of lymphoma, future studies should aim for broader and more collaborative international research efforts.}, } @article {pmid39756021, year = {2025}, author = {Akaree, N and Secco, V and Levy-Adam, F and Younis, A and Carra, S and Shalgi, R}, title = {Regulation of physiological and pathological condensates by molecular chaperones.}, journal = {The FEBS journal}, volume = {292}, number = {13}, pages = {3271-3297}, pmid = {39756021}, issn = {1742-4658}, support = {//AriSLA/ ; //Giovanni Armenise Harvard Foundation/ ; HT94252310319//Congressionally Directed Medical Research Programs/ ; AHA-MCA 2022//AriAlzh/ ; //Rappaport Family Institute for Research in Medical Sciences/ ; //Prince Center for Neurodegenerative Disorders of the Brain/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology ; *Stress Granules/metabolism/pathology/genetics ; *Molecular Chaperones/metabolism/genetics ; *Frontotemporal Dementia/genetics/metabolism/pathology ; RNA-Binding Protein FUS/genetics/metabolism ; Animals ; *Biomolecular Condensates/metabolism/genetics ; DNA-Binding Proteins/genetics/metabolism ; *Protein Aggregation, Pathological/genetics/metabolism/pathology ; Heterogeneous Nuclear Ribonucleoprotein A1/genetics/metabolism ; }, abstract = {Biomolecular condensates are dynamic membraneless compartments that regulate a myriad of cellular functions. A particular type of physiological condensate called stress granules (SGs) has gained increasing interest due to its role in the cellular stress response and various diseases. SGs, composed of several hundred RNA-binding proteins, form transiently in response to stress to protect mRNAs from translation and disassemble when the stress subsides. Interestingly, SGs contain several aggregation-prone proteins, such as TDP-43, FUS, hnRNPA1, and others, which are typically found in pathological inclusions seen in autopsy tissues from amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) patients. Moreover, mutations in these genes lead to the familial form of ALS and FTD. This has led researchers to propose that pathological aggregation is seeded by aberrant SGs: SGs that fail to properly disassemble, lose their dynamic properties, and become pathological condensates which finally 'mature' into aggregates. Here, we discuss the evidence supporting this model for various ALS/FTD-associated proteins. We further continue to focus on molecular chaperone-mediated regulation of ALS/FTD-associated physiological condensates on one hand, and pathological condensates on the other. In addition to SGs, we review ALS/FTD-relevant nuclear condensates, namely paraspeckles, anisosomes, and nucleolar amyloid bodies, and discuss their emerging regulation by chaperones. As the majority of chaperoning mechanisms regulate physiological condensate disassembly, we highlight parallel themes of physiological and pathological condensation regulation across different chaperone families, underscoring the potential for early disease intervention.}, } @article {pmid39755715, year = {2025}, author = {Liu, Q and Sun, Y and He, B and Chen, H and Wang, L and Wang, G and Zhang, K and Zhao, X and Zhang, X and Shen, D and Zhang, X and Cui, L}, title = {Gain-of-function ANXA11 mutation cause late-onset ALS with aberrant protein aggregation, neuroinflammation and autophagy impairment.}, journal = {Acta neuropathologica communications}, volume = {13}, number = {1}, pages = {2}, pmid = {39755715}, issn = {2051-5960}, support = {2021-I2M-1-034//the Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences/ ; 2021-I2M-1-034//the Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences/ ; 2022YFC2703904//National Key Research and Development Program/ ; 2022YFC2703900//National Key Research and Development Program/ ; 2022-PUMCH-B-017//National High Level Hospital Clinical Research Funding/ ; 81971293//National Natural Science Foundation of China/ ; 82201562//National Natural Science Foundation of China/ ; XDB39040000//Strategic Priority Research Program (Pilot study) "Biological basis of aging and therapeutic strategies" of the Chinese Academy of Sciences/ ; }, mesh = {Animals ; *Autophagy/genetics ; *Amyotrophic Lateral Sclerosis/genetics/pathology/metabolism ; Mice ; Humans ; Male ; *Gain of Function Mutation ; Neuroinflammatory Diseases/pathology/genetics/metabolism ; Female ; Annexins/genetics/metabolism ; Mice, Transgenic ; Protein Aggregation, Pathological/genetics/pathology/metabolism ; Motor Neurons/pathology/metabolism ; Middle Aged ; Age of Onset ; Protein Aggregates ; RNA-Binding Proteins/genetics/metabolism ; Mice, Inbred C57BL ; }, abstract = {Mutations in the ANXA11 gene, encoding an RNA-binding protein, have been implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS), but the underlying in vivo mechanisms remain unclear. This study examines the clinical features of ALS patients harboring the ANXA11 hotspot mutation p.P36R, characterized by late-onset motor neuron disease and occasional multi-system involvement. To elucidate the pathogenesis, we developed a knock-in mouse model carrying the p.P36R mutation. In both heterozygous and homozygous mutant mice, ANXA11 protein levels were comparable to those in wild-type. Both groups exhibited late-onset motor dysfunction at approximately 10 months of age, with similar survival rates to wild-type (> 24 months) and no signs of dementia. Pathological analysis revealed early abnormal aggregates in spinal cord motor neurons, cortical neurons, and muscle cells of homozygous mice. From 2 months of age, we observed mislocalized ANXA11 aggregates, SQSTM1/p62-positive inclusions, and cytoplasmic TDP-43 mislocalization, which intensified with disease progression. Importantly, mutant ANXA11 co-aggregated with TDP-43 and SQSTM1/p62-positive inclusions. Electron microscopy of the gastrocnemius muscle uncovered myofibrillar abnormalities, including sarcomeric disorganization, Z-disc dissolution, and subsarcolemmal electron-dense structures within autophagic vacuoles. Autophagic flux, initially intact at 2 months, was impaired by 9 months, as evidenced by decreased Beclin-1 and LC3BII/I levels and increased SQSTM1/p62 expression, coinciding with mTORC1 hyperactivation. Significant motor neuron loss and neuroinflammation were detected by 9 months, with marked muscle dystrophy apparent by 12 months compared to wild-type controls. These findings implicate the gain-of-function ANXA11 mutation drives late-onset motor neuron disease by early presymptomatic proteinopathy, progressive neuronal degeneration, neuroinflammation, and autophagic dysfunction.}, } @article {pmid39753993, year = {2025}, author = {Cheng, L and Liu, Z and Shen, C and Xiong, Y and Shin, SY and Hwang, Y and Yang, SB and Chen, Z and Zhang, X}, title = {A Wonderful Journey: The Diverse Roles of Adenosine Deaminase Action on RNA 1 (ADAR1) in Central Nervous System Diseases.}, journal = {CNS neuroscience & therapeutics}, volume = {31}, number = {1}, pages = {e70208}, pmid = {39753993}, issn = {1755-5949}, support = {20224BAB216045//Youth Foundation of Natural Science Foundation of Jiangxi Province/ ; GJJ211812//Science and Technology Project Funded by the Education Department of Jiangxi Province/ ; GJJ211813//Science and Technology Project Funded by the Education Department of Jiangxi Province/ ; 202131084//Jiangxi Provincial Health Commission Science and Technology Plan Project/ ; 202211982//Jiangxi Provincial Health Commission Science and Technology Plan Project/ ; RZYB202201//Research project of Cognitive Science and Transdisciplinary Studies Center of Jiangxi Province/ ; 20224BAB206040//Provincial Natural Science Foundation of Jiangxi Province/ ; 202411843024//Foundation of Students' Platform for Innovation and Entrepreneurship Training Program/ ; S202411843050//Foundation of Students' Platform for Innovation and Entrepreneurship Training Program/ ; 2022B1010//Administration of Traditional Chinese Medicine of Jiangxi Province/ ; }, mesh = {*Adenosine Deaminase/genetics/metabolism ; Humans ; Animals ; *RNA-Binding Proteins/metabolism/genetics ; *Central Nervous System Diseases/genetics/metabolism/therapy ; RNA Editing ; }, abstract = {BACKGROUND: Adenosine deaminase action on RNA 1 (ADAR1) can convert the adenosine in double-stranded RNA (dsRNA) molecules into inosine in a process known as A-to-I RNA editing. ADAR1 regulates gene expression output by interacting with RNA and other proteins; plays important roles in development, including growth; and is linked to innate immunity, tumors, and central nervous system (CNS) diseases.

RESULTS: In recent years, the role of ADAR1 in tumors has been widely discussed, but its role in CNS diseases has not been reviewed. It is worth noting that recent studies have shown ADAR1 has great potential in the treatment of neurodegenerative diseases, but the mechanisms are still unclear. Therefore, it is necessary to elaborate on the role of ADAR1 in CNS diseases.

CONCLUSIONS: Here, we focus on the effects and mechanisms of ADAR1 on CNS diseases such as Aicardi-AicardiGoutières syndrome, Alzheimer's disease, Parkinson's disease, glioblastoma, epilepsy, amyotrophic lateral sclerosis, and autism. We also evaluate the impact of ADAR1-based treatment strategies on these diseases, with a particular focus on the development and treatment strategies of new technologies such as microRNAs, nanotechnology, gene editing, and stem cell therapy. We hope to provide new directions and insights for the future development of ADAR1 gene editing technology in brain science and the treatment of CNS diseases.}, } @article {pmid39753665, year = {2025}, author = {Quintanilla, CA and Fitzgerald, Z and Kashow, O and Radojicic, MS and Ulupinar, E and Bitlis, D and Genc, B and Andjus, P and van Drongelen, W and Ozdinler, PH}, title = {High-density multielectrode arrays bring cellular resolution to neuronal activity and network analyses of corticospinal motor neurons.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {732}, pmid = {39753665}, issn = {2045-2322}, support = {778405 "AUTOIGG"//EU H2020 MSCA RISE/ ; R01 AG061708/AG/NIA NIH HHS/United States ; 4242 "NIMOCHIP"//Science Fund of the Republic of Serbia/ ; R01AG061708-03/NH/NIH HHS/United States ; 5T32NS041234-18/NH/NIH HHS/United States ; }, mesh = {Animals ; *Motor Neurons/physiology ; Mice ; *Microelectrodes ; Motor Cortex/physiology ; Pyramidal Tracts/physiology ; Nerve Net/physiology ; Mice, Transgenic ; }, abstract = {Corticospinal motor neurons (CSMN), located in the motor cortex of the brain, are one of the key components of the motor neuron circuitry. They are in part responsible for the initiation and modulation of voluntary movement, and their degeneration is the hallmark for numerous diseases, such as amyotrophic lateral sclerosis (ALS), hereditary spastic paraplegia, and primary lateral sclerosis. Cortical hyperexcitation followed by in-excitability suggests the early involvement of cortical dysfunction in ALS pathology. However, a high-spatiotemporal resolution on our understanding of their functional health and connectivity is lacking. Here, we combine optical imaging with high-density microelectrode array (HD-MEA) system enabling single cell resolution and utilize UCHL1-eGFP mice to bring cell-type specificity to our understanding of the electrophysiological features of healthy CSMN, as they mature and form network connections with other cortical neurons, in vitro. This novel approach lays the foundation for future cell-type specific analyses of CSMN that are diseased due to different underlying causes with cellular precision, and it will allow the assessment of their functional response to compound treatment, especially for drug discovery efforts in upper motor neuron diseases.}, } @article {pmid39753643, year = {2025}, author = {Mravinacová, S and Bergström, S and Olofsson, J and de San José, NG and Anderl-Straub, S and Diehl-Schmid, J and Fassbender, K and Fliessbach, K and Jahn, H and Kornhuber, J and Landwehrmeyer, GB and Lauer, M and Levin, J and Ludolph, AC and Prudlo, J and Schneider, A and Schroeter, ML and Wiltfang, J and Steinacker, P and , and Otto, M and Nilsson, P and Månberg, A}, title = {Addressing inter individual variability in CSF levels of brain derived proteins across neurodegenerative diseases.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {668}, pmid = {39753643}, issn = {2045-2322}, mesh = {Humans ; *Neurodegenerative Diseases/cerebrospinal fluid/diagnosis ; *Biomarkers/cerebrospinal fluid ; Male ; Female ; Aged ; Middle Aged ; Brain/metabolism/pathology ; Alzheimer Disease/cerebrospinal fluid/diagnosis ; Cerebrospinal Fluid Proteins/analysis ; Amyotrophic Lateral Sclerosis/cerebrospinal fluid/diagnosis ; }, abstract = {Accurate diagnosis and monitoring of neurodegenerative diseases require reliable biomarkers. Cerebrospinal fluid (CSF) proteins are promising candidates for reflecting brain pathology; however, their diagnostic utility may be compromised by natural variability between individuals, weakening their association with disease. Here, we measured the levels of 69 pre-selected proteins in cerebrospinal fluid using antibody-based suspension bead array technology in a multi-disease cohort of 499 individuals with neurodegenerative disorders including Alzheimer's disease (AD), behavioral variant frontotemporal dementia, primary progressive aphasias, amyotrophic lateral sclerosis (ALS), corticobasal syndrome, primary supranuclear palsy, along with healthy controls. We identify significant inter-individual variability in overall CSF levels of brain-derived proteins, which could not be attributed to specific disease associations. Using linear modelling, we show that adjusting for median CSF levels of brain-derived proteins increases the diagnostic accuracy of proteins previously identified as altered in CSF in the context of neurodegenerative disorders. We further demonstrate a simplified approach for the adjustment using pairs of correlated proteins with opposite alteration in the diseases. With this approach, the proteins adjust for each other and further increase the biomarker performance through additive effect. When comparing the diseases, two proteins-neurofilament medium and myelin basic protein-showed increased levels in ALS compared to other diseases, and neurogranin showed a specific increase in AD. Several other proteins showed similar trends across the studied diseases, indicating that these proteins likely reflect shared processes related to neurodegeneration. Overall, our findings suggest that accounting for inter-individual variability is crucial in future studies to improve the identification and performance of relevant biomarkers. Importantly, we highlight the need for multi-disease studies to identify disease-specific biomarkers.}, } @article {pmid39753538, year = {2025}, author = {Larrea, D and Tamucci, KA and Kabra, K and Velasco, KR and Yun, TD and Pera, M and Montesinos, J and Agrawal, RR and Paradas, C and Smerdon, JW and Lowry, ER and Stepanova, A and Yoval-Sanchez, B and Galkin, A and Wichterle, H and Area-Gomez, E}, title = {Altered mitochondria-associated ER membrane (MAM) function shifts mitochondrial metabolism in amyotrophic lateral sclerosis (ALS).}, journal = {Nature communications}, volume = {16}, number = {1}, pages = {379}, pmid = {39753538}, issn = {2041-1723}, support = {R21 NS125466/NS/NINDS NIH HHS/United States ; R01 NS131322/NS/NINDS NIH HHS/United States ; R01 AG056387/AG/NIA NIH HHS/United States ; F31 NS095571/NS/NINDS NIH HHS/United States ; S10 OD030335/OD/NIH HHS/United States ; T32 DK007647/DK/NIDDK NIH HHS/United States ; R01 NS112381/NS/NINDS NIH HHS/United States ; }, mesh = {*Amyotrophic Lateral Sclerosis/metabolism/genetics ; *Endoplasmic Reticulum/metabolism ; *Mitochondria/metabolism ; Humans ; Animals ; Spinal Cord/metabolism ; Mice ; Glucose/metabolism ; Fatty Acids/metabolism ; Male ; Energy Metabolism ; Pyruvic Acid/metabolism ; Intracellular Membranes/metabolism ; Electron Transport Complex I/metabolism/genetics ; Brain/metabolism ; Mitochondria Associated Membranes ; }, abstract = {Mitochondrial function is modulated by its interaction with the endoplasmic reticulum (ER). Recent research indicates that these contacts are disrupted in familial models of amyotrophic lateral sclerosis (ALS). We report here that this impairment in the crosstalk between mitochondria and the ER impedes the use of glucose-derived pyruvate as mitochondrial fuel, causing a shift to fatty acids to sustain energy production. Over time, this deficiency alters mitochondrial electron flow and the active/dormant status of complex I in spinal cord tissues, but not in the brain. These findings suggest mitochondria-associated ER membranes (MAM domains) play a crucial role in regulating cellular glucose metabolism and that MAM dysfunction may underlie the bioenergetic deficits observed in ALS.}, } @article {pmid39753182, year = {2025}, author = {Swarup, G and Medchalmi, S and Ramachandran, G and Sayyad, Z}, title = {Molecular aspects of cytoprotection by Optineurin during stress and disease.}, journal = {Biochimica et biophysica acta. Molecular cell research}, volume = {1872}, number = {3}, pages = {119895}, doi = {10.1016/j.bbamcr.2024.119895}, pmid = {39753182}, issn = {1879-2596}, mesh = {Humans ; Membrane Transport Proteins ; Cell Cycle Proteins ; Animals ; *Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology ; *Transcription Factor TFIIIA/genetics/metabolism ; *Cytoprotection ; Endoplasmic Reticulum Stress ; Signal Transduction ; Oxidative Stress ; Autophagy ; *Glaucoma/genetics/metabolism/pathology ; *Neurodegenerative Diseases/genetics/metabolism/pathology ; }, abstract = {Optineurin/OPTN is an adapter protein that plays a crucial role in mediating many cellular functions, including autophagy, vesicle trafficking, and various signalling pathways. Mutations of OPTN are linked with neurodegenerative disorders, glaucoma, and amyotrophic lateral sclerosis (ALS). Recent work has shown that OPTN provides cytoprotection from many types of stress, including oxidative stress, endoplasmic reticulum stress, protein homeostasis stress, tumour necrosis factor α, and microbial infection. Here, we discuss the mechanisms involved in cytoprotective functions of OPTN, which possibly depend on its ability to modulate various stress-induced signalling pathways. ALS- and glaucoma-causing mutants of OPTN are altered in this regulation, which may affect cell survival, particularly under various stress conditions. We suggest that OPTN deficiency created by mutations may cooperate with stress-induced signalling to enhance or cause neurodegeneration. Other functions of OPTN, such as neurotrophin secretion and vesicle trafficking, may also contribute to cytoprotection.}, } @article {pmid39752797, year = {2025}, author = {Ju, W and Min, YG and Kim, JS and Ryu, S and Ahn, SW and Hong, YH and Choi, SJ and Sung, JJ}, title = {Clinical features of FOSMN syndrome in Korea: A comparative analysis with bulbar-onset amyotrophic lateral sclerosis.}, journal = {Journal of the neurological sciences}, volume = {469}, number = {}, pages = {123372}, doi = {10.1016/j.jns.2024.123372}, pmid = {39752797}, issn = {1878-5883}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/epidemiology/diagnosis/physiopathology/therapy ; Male ; Female ; Middle Aged ; Republic of Korea/epidemiology ; Aged ; Adult ; *Facial Nerve Diseases/epidemiology/diagnosis/physiopathology/therapy ; Age of Onset ; Cohort Studies ; Disease Progression ; }, abstract = {Facial onset sensory and motor neuronopathy (FOSMN) syndrome is a rare neurodegenerative disorder initially characterized by facial sensory deficits, which later progress to motor deficits in a rostral-caudal distribution. This study investigated the prevalence, clinical features, and prognosis of FOSMN syndrome and compared these aspects with those of bulbar-onset amyotrophic lateral sclerosis (ALS) within a single institutional cohort of motor neuron diseases. We identified four patients with FOSMN syndrome who had been misclassified as having bulbar-onset ALS, representing approximately 2 % of such ALS cases. The median age of onset for FOSMN syndrome was similar to that of bulbar-onset ALS. However, patients with FOSMN syndrome were often diagnosed at more advanced stages and had lower ALS Functional Rating Scale-revised (ALSFRS-R) scores. Despite the slower progression of FOSMN syndrome, therapeutic interventions such as gastrostomy or non-invasive ventilation were frequently required. In conclusion, this study provides detailed clinical profiles of patients with FOSMN syndrome and deepens our understanding of a heterogeneous group of neurodegenerative disorders.}, } @article {pmid39751824, year = {2025}, author = {Sghaier, I and Kacem, I and Ratti, A and Takout, K and Abida, Y and Peverelli, S and Ticozzi, N and Gargouri-Berrachid, A and Silani, V and Gouider, R}, title = {Impact of APOE and MAPT genetic profile on the cognitive functions among Amyotrophic Lateral Sclerosis Tunisian patients.}, journal = {Journal of neural transmission (Vienna, Austria : 1996)}, volume = {132}, number = {4}, pages = {609-618}, pmid = {39751824}, issn = {1435-1463}, mesh = {Humans ; Tunisia ; *Amyotrophic Lateral Sclerosis/genetics/complications/psychology ; Male ; Female ; *tau Proteins/genetics ; Middle Aged ; Aged ; *Apolipoproteins E/genetics ; Adult ; *Cognitive Dysfunction/genetics/etiology ; Genotype ; }, abstract = {Amyotrophic Lateral Sclerosis(ALS) has traditionally been managed as a neuromuscular disorder. However, recent evidence suggests involvement of non-motor domains. This study aims to evaluate the impact of APOE and MAPT genotypes on the cognitive features of ALS. We included confirmed ALS cases from the Neurology department at Razi University Hospital, Tunisia. APOE and MAPT screening were conducted with Sanger sequencing validation, and preliminary screening for four main ALS genes was performed. Clinical phenotypes and genotypes were analyzed using appropriate tests, with healthy controls (HC) representing the Tunisian population. Two-hundred-seventy ALS patients were included, stratified as 213 spinal cases,49 with bulbar onset and 8 patients with generalized form with 140 HC. Regarding APOE, we reported high frequency of ALS cases carrier of APOE-ε4 isoform compared to controls(p < 0.0001).We found a significant association between APOE-ɛ4 and ALS onset site (p = 0.05,r = 0.33),with higher frequencies in bulbar onset patients. Cognitive signs were more frequent in ɛ4 carriers (r = 0.43,p < 0.01),and a significant link was observed between dysexecutive functions and the APOE risk allele (p = 0.0495).Concerning the MAPT haplotypes, we reported high frequency of ALS cases carrier of MAPT H1-haplotype HC (94.45% and 72.14% respectively, p < 0.001).Among ALS cases,MAPT-H1 showed a stronger positive correlation with the presence of oculomotor signs(p = 0.05,r = 0.28).As well as significant positive association between cognitive impairments(p = 0.039,r = 0.59). Our findings emphasize the correlation between APOE and MAPT genotypes and the cognitive features in our ALS patients. We also observed other interesting, though weak, significant correlations (with coefficients not exceeding 0.20),which require further validation in a larger cohort to confirm our results.}, } @article {pmid39749679, year = {2025}, author = {Young, CA and Chaouch, A and Mcdermott, CJ and Al-Chalabi, A and Chhetri, SK and Bidder, C and Edmonds, E and Ellis, C and Annadale, J and Wilde, L and Sharrack, B and Malaspina, A and Leach, O and Mills, R and Tennant, A}, title = {Determinants and progression of stigma in amyotrophic lateral sclerosis/motor neuron disease.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {26}, number = {3-4}, pages = {192-202}, pmid = {39749679}, issn = {2167-9223}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/psychology/diagnosis/epidemiology ; Male ; Female ; Middle Aged ; *Social Stigma ; Aged ; Disease Progression ; Self Concept ; Quality of Life/psychology ; Adult ; Fatigue/psychology ; *Motor Neuron Disease/psychology ; }, abstract = {Objective: Stigma in amyotrophic lateral sclerosis/motor neurone disease (ALS/MND) may be felt or enacted; felt stigma covers feeling devalued by the illness, whereas enacted stigma refers to being treated differently because of it. Stigma in ALS/MND has been shown to increase social withdrawal, worsen quality of life, and reduce use of assistive devices, so we explored prevalence and factors influencing stigma. Methods: Participants in the Trajectories of Outcome in Neurological Conditions-ALS study completed scales measuring stigma, fatigue, spasticity, functioning, mood, worry, self-esteem, and perceived health, as well as demographic information and symptoms like head drop or emotional lability. Following transformation to interval-scale estimates, data were analyzed by regression, structural equation modeling, and trajectory models. Results: Stigma was experienced by 83.5% of 1059 respondents. Worry, disease severity (King's stage ≥ 3), emotional lability, fatigue, spasticity, and bulbar onset increase stigma. In contrast, increasing age, living with spouse/partner, and greater self-esteem were associated with reduced stigma. Trajectory analysis over 30 months (N = 1049) showed three groups, the largest (70.2%) had high levels of stigma which significantly increased during follow-up. In a recently diagnosed subset of 347 participants, stigma was experienced early in the disease course (<7 months after diagnosis), and for 77.2% stigma significantly increased over time. Conclusions: Both felt and enacted stigma are frequently perceived by people living with ALS/MND. Younger people and those with bulbar onset, emotional lability, worry, fatigue, and spasticity, or at more advanced clinical stages, are at greater risk.}, } @article {pmid39749674, year = {2025}, author = {Tankéré, P and Cascarano, E and Saint Raymond, C and Mallaret, M and Toribio Ruiz, C and Herquelot, E and Denis, H and Cals Maurette, M and Tamisier, R and Pépin, JL}, title = {Care trajectories and adherence to respiratory management recommendations in persons living with amyotrophic lateral sclerosis: a ten-year cohort study in a French tertiary university centre.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {26}, number = {3-4}, pages = {259-267}, doi = {10.1080/21678421.2024.2447911}, pmid = {39749674}, issn = {2167-9223}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy/mortality/epidemiology/complications ; Male ; Female ; Middle Aged ; Aged ; Tertiary Care Centers ; France/epidemiology ; *Noninvasive Ventilation/methods ; Cohort Studies ; *Respiratory Insufficiency/therapy/etiology ; Prospective Studies ; }, abstract = {Objective: This study determined real-life care trajectories before and after initiation of noninvasive ventilation (NIV) in patients with amyotrophic lateral sclerosis (ALS). Caregiver adherence to respiratory management recommendations and the associated survival rate of people with ALS were also assessed. Methods: Data were obtained from a tertiary center prospective ALS database that included 10 years of follow-up data for people with ALS. Results are presented numerically and with graphical time sequence analysis through K clustering (TAK) representation. Kaplan Meier and Cox models were used to determine survival and associated prognostic factors. Results: 109 patients with ALS patients were included; median [interquartile range] follow-up was 25.0 months [15.3-43.3]. During study timeframe patients had a median of 4.0 [2.0-6.0] clinical visits; death occurred in 54.1%. Median time between clinical visits was 3.9 [2.8-6.5] months, between arterial blood gases was 4.3 months [3.0-6.6], between spirometry testing was 5.8 months [4.1-8.2], and between nocturnal oximetry was 4.4 months [3.0-7.8]. Visualization of care trajectories TAK show marked heterogeneity in survival, time to NIV initiation, and time from NIV initiation to death. Mortality was correlated with NIV initiation and arterial carbon dioxide pressure increase. Conclusions: The current framework in ALS guidelines should be adapted to the ALS disease stage and individual patient characteristics. Understanding how subgroups of patients with ALS use healthcare services over time could help to highlight fragility areas and priorities in the allocation of care resources and implementation of best practices.}, } @article {pmid39749668, year = {2025}, author = {Mehta, P and Raymond, J and Nair, T and Han, M and Berry, J and Punjani, R and Larson, T and Mohidul, S and Horton, DK}, title = {Amyotrophic lateral sclerosis estimated prevalence cases from 2022 to 2030, data from the national ALS Registry.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {26}, number = {3-4}, pages = {290-295}, doi = {10.1080/21678421.2024.2447919}, pmid = {39749668}, issn = {2167-9223}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/epidemiology/diagnosis ; *Registries ; Male ; Female ; Prevalence ; Aged ; Middle Aged ; United States/epidemiology ; Adult ; Aged, 80 and over ; Retrospective Studies ; Young Adult ; Adolescent ; }, abstract = {Objective: To estimate the projected number of ALS cases in the United States from 2022 to 2030. Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neuromuscular disease with no known cure. Because ALS is not a notifiable disease in the United States, the accurate ascertainment of prevalent ALS cases continues to be a challenge. To overcome this, the National ALS Registry (Registry) uses novel methods to estimate newly diagnosed and existing cases in the United States. Methods: We estimated ALS prevalence retrospectively from 2022 to 2024 and prospectively from 2025 to 2030 using prevalence obtained through previous CRC analyses on 2018 Registry data (the most current data available) to generate projected observed, missing, and total cases. Projected prevalent cases were then stratified by age, race, and sex. Results: The number of estimated ALS cases in 2022 was 32,893. By 2030, projected cases increase more than 10%, to 36,308. The largest increase occurs for the population ages 66 years and older, with a 25% increase (from 16,349 cases in 2022 to 20,438 cases in 2030). The projected number of cases classified as "other race" will increase by 15% (from 2,473 cases in 2022 to 2,854 cases in 2030). Conclusions: These estimates of projected ALS cases reflect anticipated changes in the underlying demographics of the United States. Our projections are likely an underestimation because emerging therapeutics and improved healthcare will improve survivability in this vulnerable population. These results should inform policy to more efficiently allocate resources for ALS patients and programs.}, } @article {pmid39749172, year = {2024}, author = {Chauhan, A and Begum, J and Lavanya, KM and Gupta, A and Ghosh, S and Kulkarni, S}, title = {Experiential Learning of Active Learning Strategies in Mentor Learner Web-based Discussions: A Perceptions Study.}, journal = {International journal of applied & basic medical research}, volume = {14}, number = {4}, pages = {258-265}, pmid = {39749172}, issn = {2229-516X}, abstract = {BACKGROUND: Active learning strategies (ALSs) in medical education are valued for their effectiveness but face adoption challenges among educators, underscoring the need for a deeper understanding of their implementation and impact.

AIM: The aim of the study was to investigate the perceptions of medical educators regarding the effectiveness and challenges of ALS through mentor-learner (ML) web-based discussions.

SETTINGS AND DESIGN: The retrospective cross-sectional study analyzed data from 32 medical educators enrolled in the Foundation for Advancement of International Medical Education Research course at Christian Medical College, Ludhiana. It utilized a mixed-method approach, gathering both quantitative and qualitative data through ML web discussions.

MATERIALS AND METHODS: The study used a "dual-method" approach, combining traditional online discussions with a "role-reversal" method on an ML web platform, promoting experiential learning. Participant responses on ALS implementation tasks were collected and analyzed within these discussions.

RESULTS: Participants shared various ALS for collaborative learning (20), classroom engagement (26), assessing prior knowledge (12), and note-taking during lectures (10). Further, among the 11 ALS examined, the ease of implementation varied significantly among participants (P < 0.0001). Challenges in ALS implementation included inadequate faculty training (91%), motivation (84%), resource constraints (81%), student (75%), and administrative resistance (69%). Four themes emerged as recommendations for effective ALS implementation: empowering educators, engaging students, streamlining support systems, and monitoring impact.

CONCLUSION: The study highlights a mixed perspective of medical educators on ALS. Although ALS was perceived as effective in fostering critical thinking and developing collaborative learning among students, various challenges, such as a lack of skilled faculty and resources, necessitated robust faculty development initiatives.}, } @article {pmid39748876, year = {2025}, author = {Salter, S and Salter, E and Kim, AJ and Liu, AK}, title = {Rising Voltage-Gated Potassium Channel Antibody Level as a Possible Disease Progression Marker for Amyotrophic Lateral Sclerosis: A Case Report.}, journal = {Cureus}, volume = {17}, number = {1}, pages = {e76760}, pmid = {39748876}, issn = {2168-8184}, abstract = {A subset of amyotrophic lateral sclerosis (ALS) patients tests positive for antibodies commonly associated with autoimmune neurological diseases, including voltage-gated potassium channel (VGKC)-complex antibodies. Although an autoimmune basis for ALS remains speculative, and immunomodulatory therapies have shown minimal benefit as of yet, isolated cases suggest that VGKC-complex antibodies may be relevant to disease type and progression. In this report, we present a case of ALS in which increasing VGKC-complex antibody levels correlated with clinical decline, raising the question of whether such antibodies could serve as biomarkers of progression in VGKC-complex antibody-positive ALS patients. To date, no published studies have systematically evaluated changes in VGKC-complex antibody levels in ALS patients over time. Our findings suggest that tracking VGKC-complex antibodies in ALS may offer insights into disease progression and prompt further investigation into their potential role as prognostic biomarkers, especially in certain subtypes of the disease.}, } @article {pmid39748816, year = {2024}, author = {Li, Z and Liu, X and Zhang, H and Li, P and Yao, F}, title = {Improving resistance to lepidopteran pests and herbicide using Sanming dominant genic male sterile rice (Oryza sativa L.).}, journal = {Frontiers in plant science}, volume = {15}, number = {}, pages = {1525620}, pmid = {39748816}, issn = {1664-462X}, abstract = {In order to improve both resistance to lepidopteran pests and resistance to the herbicide imazethapyr in mainstay japonica varieties of the Huang-Huai rice region, Sanming dominant genic male sterile (S-DGMS) rice was used as a platform to facilitate the pyramiding of functional genes and the replacement of the genomic background. Twelve novel lines were developed, each carrying a crystal toxin gene conferring resistance to lepidopteran pests and the ALS[627N] allele conferring resistance to herbicide imazethapyr in the background of a mainstay japonica variety. The genomic background of the 12 novel lines was examined using 48 specified molecular markers, and each line carried less than two polymorphic markers relative to the corresponding mainstay variety. All 12 lines displayed high resistance to lepidopteran pests and the herbicide imazethapyr. The major agronomic traits of the 12 lines showed no difference relative to the responding mainstay variety when sprayed with pesticide. The popularization of the 12 japonica lines could reduce the use of pesticides and provide highly efficient control of weeds and weedy rice in the future, thus promoting the development of japonica rice production. Therefore, S-DGMS rice could be a powerful tool for the genetic improvement of target traits in rice.}, } @article {pmid39748214, year = {2025}, author = {Brown, G and Jesus, S and Leboffe, E and Esch, A and Newport, K}, title = {Advance Care Planning Billing Codes Associated With Decreased Healthcare Utilization in Neurological Disease.}, journal = {Journal of healthcare management / American College of Healthcare Executives}, volume = {70}, number = {1}, pages = {58-73}, pmid = {39748214}, issn = {1096-9012}, mesh = {Humans ; Aged ; Male ; Female ; *Advance Care Planning/statistics & numerical data ; United States ; *Nervous System Diseases/therapy ; Aged, 80 and over ; *Patient Acceptance of Health Care/statistics & numerical data ; Cohort Studies ; }, abstract = {GOALS: Advance care planning (ACP) procedure codes have been established to reimburse meaningful care goal discussions; however, the utilization frequency of these codes in neurological disease is unknown. The objective of this study is to identify the association between ACP codes and healthcare utilization in chronic neurodegenerative diseases.

METHODS: This is a multicenter cohort study using real-world electronic health data. Using the TriNetX database, we collected electronic health data from 92 institutions in the United States. We included patients aged 65 and older who had been diagnosed with one of four neurological diseases: Alzheimer's disease, Parkinson's disease, multiple sclerosis, or amyotrophic lateral sclerosis (ALS). Patients with congestive heart failure were included as a reference. From the 64,683,009 total patients in the database, 877,138 had Alzheimer's disease, 544,610 had Parkinson's disease, 208,341 had multiple sclerosis, 9,944 had amyotrophic lateral sclerosis, and 1,500,186 had congestive heart failure. For each disease, we compared hospitalizations and emergency department (ED) visits over a two-year period between patients with and without ACP codes documented. Then, in patients with ACP, we investigated the rates of hospitalizations and ED visits over the two years before ACP and two years after ACP to understand the impact of ACP on the healthcare utilization trend. All patients had records for at least two years after index.

PRINCIPAL FINDINGS: The rate of ACP code documentation ranged from 1.8% of multiple sclerosis patients to 3.6% of Alzheimer's disease patients. After matching for demographic and health variables, usage of ACP codes was associated with significantly fewer hospitalizations for Alzheimer's disease patients. Across all diseases, there was a 20% to 30% decrease in ED visits, which was significant. Furthermore, there was a significant change in the trend of hospitalizations and ED visits for patients after ACP documentation. Patients went from increasing utilization before ACP documentation to decreasing utilization after documentation.

PRACTICAL APPLICATIONS: ACP billing codes are used infrequently in neurological disease, which may indicate that reimbursement alone is not sufficient to drive code usage. Usage of ACP billing codes was associated with decreased healthcare utilization, particularly in terms of ED visits. Beyond the primary objective of providing goal-concordant care, ACP may impact the economic burden of chronic neurodegenerative disease, which has high costs of care in our aging society. There may be particular benefits with Alzheimer's disease, which had an impact on both hospitalizations and ED visits and is the most prevalent neurodegenerative disease. Future work is needed to better understand the best implementation strategy for ACP in a multifaceted approach that emphasizes patient care preferences for their illness.}, } @article {pmid39747792, year = {2025}, author = {Lee, J and Kouznetsova, VL and Kesari, S and Tsigelny, I}, title = {Selective diagnostics of Amyotrophic Lateral Sclerosis, Alzheimer's and Parkinson's Diseases with machine learning and miRNA.}, journal = {Metabolic brain disease}, volume = {40}, number = {1}, pages = {79}, pmid = {39747792}, issn = {1573-7365}, mesh = {*MicroRNAs/genetics ; Humans ; *Amyotrophic Lateral Sclerosis/genetics/diagnosis/metabolism ; *Machine Learning ; *Alzheimer Disease/diagnosis/genetics/metabolism ; *Parkinson Disease/diagnosis/genetics/metabolism ; *Biomarkers ; }, abstract = {The diagnosis of neurological diseases can be expensive, invasive, and inaccurate, as it is often difficult to distinguish between different types of diseases with similar motor symptoms. However, the dysregulation of miRNAs can be used to create a robust machine-learning model for a reliable diagnosis of neurological diseases. We used miRNA sequence descriptors and gene target data to create machine-learning models that can be used as diagnostic tools. The top-performing machine-learning models, trained on filtered miRNA datasets for Amyotrophic Lateral Sclerosis, Alzheimer's and Parkinson's Diseases of this research yielded 94, 97, and 96, percent accuracies, respectively. Analysis of dysregulated miRNA in neurological diseases elucidated novel biomarkers that could be used to diagnose and distinguish between the diseases. Machine-learning models developed using sequence and gene target descriptors of miRNA biomarkers can achieve favorable accuracies for disease classification and attain a robust discerning capability of neurological diseases.}, } @article {pmid39747573, year = {2025}, author = {Kim, KM and Girdhar, A and Cicardi, ME and Kankate, V and Hayashi, M and Yang, R and Carey, JL and Fare, CM and Shorter, J and Cingolani, G and Trotti, D and Guo, L}, title = {NLS-binding deficient Kapβ2 reduces neurotoxicity via selective interaction with C9orf72-ALS/FTD dipeptide repeats.}, journal = {Communications biology}, volume = {8}, number = {1}, pages = {2}, pmid = {39747573}, issn = {2399-3642}, support = {R35GM138109//U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)/ ; F31 NS111870/NS/NINDS NIH HHS/United States ; R21 NS128396/NS/NINDS NIH HHS/United States ; 628389//Muscular Dystrophy Association (Muscular Dystrophy Association Inc.)/ ; R01 NS121143/NS/NINDS NIH HHS/United States ; F31NS111870//U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; R35 GM140733/GM/NIGMS NIH HHS/United States ; R35GM140733//U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)/ ; RF1NS121143//U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; R21-NS090912//U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; R21NS128396//U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; R01GM099836//U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)/ ; R21 NS090912/NS/NINDS NIH HHS/United States ; RF1 NS121143/NS/NINDS NIH HHS/United States ; T32GM008275//U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)/ ; R01 GM099836/GM/NIGMS NIH HHS/United States ; RF1 AG057882/AG/NIA NIH HHS/United States ; T32 GM008275/GM/NIGMS NIH HHS/United States ; R35 GM138109/GM/NIGMS NIH HHS/United States ; }, mesh = {*C9orf72 Protein/metabolism/genetics ; Humans ; *Amyotrophic Lateral Sclerosis/metabolism/genetics ; *Frontotemporal Dementia/metabolism/genetics ; *Dipeptides/metabolism ; beta Karyopherins/metabolism/genetics ; RNA-Binding Protein FUS/metabolism/genetics ; Protein Binding ; HEK293 Cells ; }, abstract = {Arginine-rich dipeptide repeat proteins (R-DPRs) are highly toxic proteins found in patients with C9orf72-linked amyotrophic lateral sclerosis and frontotemporal dementia (C9-ALS/FTD). R-DPRs can cause toxicity by disrupting the natural phase behavior of RNA-binding proteins (RBPs). Mitigating this abnormal phase behavior is, therefore, crucial to reduce R-DPR-induced toxicity. Here, we use FUS as a model RBP to investigate the mechanism of R-DPR-induced aberrant RBP phase transition. We find that this phase transition can be mitigated by Kapβ2. However, as a nuclear import receptor and phase modifier for PY-NLS-containing RBPs, the function of WT Kapβ2 could lead to undesired interaction with its native substrates when used as therapeutics for C9-ALS/FTD. To address this issue, it is crucial to devise effective strategies that allow Kapβ2 to selectively target its binding to the R-DPRs, instead of the RBPs. We show that NLS-binding deficient Kapβ2W460A:W730A can indeed selectively interact with R-DPRs in FUS assembly without affecting normal FUS phase separation. Importantly, Kapβ2W460A:W730A prevents enrichment of poly(GR) in stress granules and mitigates R-DPR neurotoxicity. Thus, NLS-binding deficient Kapβ2 may be implemented as a potential therapeutic for C9-ALS/FTD.}, } @article {pmid39747563, year = {2025}, author = {Adim, H and Fahmideh, L and Fakheri, BA and Zarrini, HN and Sasanfar, H}, title = {iTRAQ-based quantitative proteomic analysis of herbicide stress in Avena ludoviciana Durieu.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {577}, pmid = {39747563}, issn = {2045-2322}, mesh = {*Herbicides/pharmacology/toxicity ; *Avena/drug effects/genetics/metabolism ; *Proteomics/methods ; *Herbicide Resistance/genetics ; *Plant Proteins/metabolism/genetics ; Gene Expression Regulation, Plant/drug effects ; Stress, Physiological/drug effects ; Acetyl-CoA Carboxylase/metabolism/genetics ; }, abstract = {Winter wild oat (Avena sterilis subsp. ludoviciana (Durieu) Gillet & Magne) has been considered the most common and troublesome weed in wheat fields of Iran. The widespread and continuous use of herbicides has led to the emergence and development of resistant biotypes in A. ludoviciana, making it one of the most important herbicide-resistant weeds within field crops. Considering the importance of understanding the mechanisms underlying resistance to herbicides and identifying key proteins involved in the response to Acetyl-coenzyme A carboxylase (ACCase) and Acetolactate synthase (ALS) inhibitor herbicides in A. ludoviciana. This study aimed to identify the proteins involved in herbicide resistance in A. ludoviciana using the Isobaric Tags for Relative and Absolute Quantification (iTRAQ) technique. In this study, a total of 18,313 peptides were identified with ≤ 0.01 FDR, which could be classified into 484 protein groups. Additionally, 138 differentially expressed proteins (DEPs) were identified in the resistant biotype (R), while 93 DEPs were identified in the susceptible biotype (S). Gene Ontology (GO) analysis revealed that these DEPs mainly consisted of proteins related to photosynthesis, respiration, amino acid synthesis and translation, secondary metabolite biosynthesis, defense proteins, and detoxification. Furthermore, enrichment pathway analysis using Kyoto Encyclopedia of Genes and Genomes (KEGG) showed that the most important pathways included metabolic pathways, carbohydrate metabolism, secondary metabolites, amino acid synthesis, and photosynthesis. The function of DEPs indicated that some proteins, such as cytochrome P450, play a direct role in herbicide detoxification. Overall, the results of this study demonstrated the complex response of the resistant biotype to herbicides and its ability to increase antioxidant capacity through up-regulated detoxification proteins, particularly cytochrome P450 (Q6YSB4), and defense proteins, particularly superoxide dismutase (Q0DRV6) and polyamine oxidase (Q7XR46). In the resistant A. ludoviciana populations, in addition to the activation of enzymatic and non-enzymatic defense systems, other strategies such as reduced photosynthesis and respiration, increased transcription and translation activity, enhanced lipid metabolism, regulation of cellular processes and homeostasis, and up-regulation of proteins associated with signaling and ion channels play a role in resistance to herbicide. Overall these findings provide new insights into the role of different proteins in resistance to herbicides and contribute to a comprehensive understanding of herbicide resistance in A. ludoviciana.}, } @article {pmid39745174, year = {2025}, author = {Antonelli, S and Castañeda, FN and Olivieri, AC and Carabajal, MD and Pellegrino Vidal, RB}, title = {Novel Data Fusion Strategy for Second-Order Data: Multivariate Curve Resolution for the Determination of Pharmaceuticals by Means of Fluorimetric Measurements.}, journal = {Analytical chemistry}, volume = {97}, number = {1}, pages = {962-968}, doi = {10.1021/acs.analchem.4c05725}, pmid = {39745174}, issn = {1520-6882}, mesh = {*Fluorometry/methods ; Multivariate Analysis ; Least-Squares Analysis ; Pharmaceutical Preparations/analysis ; *Water Pollutants, Chemical/analysis ; }, abstract = {A new strategy is proposed for second-order data fusion based on the simultaneous modeling of two data sets using the multivariate curve resolution-alternating least-squares (MCR-ALS) model, applying a new constraint during the ALS stage, called "Proportionality of Scores". This approach allows for the fusion of data from different sources, without requiring common dimensionality, and enables the application of specific constraints to each data set. This strategy was applied to the determination of five pharmaceutical contaminants (naproxen, danofloxacin, ofloxacin, sarafloxacin, and enoxacin) in environmental water samples, by fusing two sets of excitation-emission fluorescence matrices, measured before and after photochemical derivatization. The predictive performance of the fused model was compared to individual PARAFAC models built for each fluorescence data set, showing that data fusion significantly increases precision and accuracy, as indicated by the elliptical joint confidence region test. Data fusion allowed improvement of relative errors of prediction, from 13-32% to 8-15% in validation samples and from 25-121% to 13-20% in real samples. The advantages of data fusion were evident in both cases, particularly in instances of substantial signal overlap between analytes or the presence of uncalibrated interferents with similar profiles, as demonstrated by the superior predictive capacity achieved through the proposed strategy.}, } @article {pmid39744204, year = {2024}, author = {Morales-Galicia, AE and Ramírez-Mejía, MM and Ponciano-Rodriguez, G and Méndez-Sánchez, N}, title = {Revolutionizing the understanding of liver disease: Metabolism, function and future.}, journal = {World journal of hepatology}, volume = {16}, number = {12}, pages = {1365-1370}, pmid = {39744204}, issn = {1948-5182}, abstract = {The intersection between metabolic-associated steatotic liver disease (MASLD) and chronic hepatitis B virus (HBV) infection is an emerging area of research with significant implications for public health and clinical practice. Wang et al's study highlights the complexities of managing patients with concurrent MASLD and HBV. The findings revealed that patients with concurrent MASLD-HBV exhibited more severe liver inflammation and fibrosis, whereas those with HBV alone presented a better lipid profile. The growing recognition of metabolic dysfunction in liver disease, reflected in the shift from nonalcoholic liver disease to MASLD, demands updates to clinical guidelines, particularly for patients with dual etiologies. Understanding the biological interactions between MASLD and HBV could lead to novel therapeutic approaches, emphasizing the need for personalized treatment strategies. The coexistence of MASLD and HBV presents therapeutic challenges, particularly in managing advanced fibrosis and cirrhosis, which are more likely in these patients. The aim of this editorial is to analyze the interaction between MASLD and HBV, highlight the pathophysiological mechanisms that exacerbate liver disease when both conditions coexist, and discuss the clinical implications of the findings of Wang et al.}, } @article {pmid39743746, year = {2025}, author = {Wang, Z and Wang, X and Li, P and Xia, H and Yang, X}, title = {Genetic associations between immune-related plasma proteins and neurodegenerative diseases.}, journal = {Neurological research}, volume = {47}, number = {2}, pages = {129-138}, doi = {10.1080/01616412.2024.2448745}, pmid = {39743746}, issn = {1743-1328}, mesh = {Humans ; *Neurodegenerative Diseases/genetics/immunology/blood ; *Blood Proteins/genetics/immunology ; Genome-Wide Association Study ; *Genetic Predisposition to Disease/genetics ; Amyotrophic Lateral Sclerosis/genetics/immunology ; Parkinson Disease/genetics/immunology ; }, abstract = {BACKGROUND: Immune dysregulation is commonly associated with neurodegenerative diseases (NDs), yet the underlying causes and mechanisms still require further investigation.

OBJECTIVE: This study investigates the correlation between immune-related plasma proteins and the risk of NDs by integrating genome-wide association study (GWAS) data for Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS) with plasma proteome analysis.

METHODS: By analyzing GWAS data for 4907 immune-related plasma proteins, this research evaluates the direct impact of plasma proteins on the risk of four NDs: AD, PD, ALS, and MS. Additionally, the study conducts an analysis of protein expression levels using single-cell RNA sequencing data.

RESULTS: We have identified plasma proteins that are closely associated with the risk of NDs. Using stringent criteria, we identified 88 proteins associated with AD, 115 with PD, 100 with ALS, and 87 with MS. Additionally, single-cell sequencing analyzed the protein expression and its distribution within different cell types in the brain.

CONCLUSIONS: Our research has demonstrated that plasma proteins may contribute to the risk of NDs, and it has also provided concrete evidence linking genetic susceptibility for these diseases to immune mechanisms. Furthermore, we found that specific proteins influence genetic variations linked to NDs risk via plasma-mediated regulation, emphasizing the importance of interactions between the brain and circulatory system.}, } @article {pmid39743546, year = {2025}, author = {Faller, KME and Chaytow, H and Gillingwater, TH}, title = {Targeting common disease pathomechanisms to treat amyotrophic lateral sclerosis.}, journal = {Nature reviews. Neurology}, volume = {21}, number = {2}, pages = {86-102}, pmid = {39743546}, issn = {1759-4766}, mesh = {Animals ; Humans ; *Amyotrophic Lateral Sclerosis/genetics/pathology/therapy ; }, abstract = {The motor neuron disease amyotrophic lateral sclerosis (ALS) is a devastating condition with limited treatment options. The past few years have witnessed a ramping up of translational ALS research, offering the prospect of disease-modifying therapies. Although breakthroughs using gene-targeted approaches have shown potential to treat patients with specific disease-causing mutations, the applicability of such therapies remains restricted to a minority of individuals. Therapies targeting more general mechanisms that underlie motor neuron pathology in ALS are therefore of considerable interest. ALS pathology is associated with disruption to a complex array of key cellular pathways, including RNA processing, proteostasis, metabolism and inflammation. This Review details attempts to restore cellular homeostasis by targeting these pathways in order to develop effective, broadly-applicable ALS therapeutics.}, } @article {pmid39743298, year = {2024}, author = {Wang, L and Liu, H and Li, L}, title = {Autophagy receptor-inspired chimeras: a novel approach to facilitate the removal of protein aggregates and organelle by autophagy degradation.}, journal = {Journal of Zhejiang University. Science. B}, volume = {25}, number = {12}, pages = {1115-1119}, pmid = {39743298}, issn = {1862-1783}, support = {81970431//the National Natural Science Foundation of China/ ; 2023JJ50136//the Hunan Provincial Natural Science Foundation of China/ ; }, mesh = {*Autophagy ; Humans ; *Neurodegenerative Diseases/metabolism ; *Protein Aggregates ; Animals ; Organelles/metabolism ; Alzheimer Disease/metabolism ; Neurons/metabolism ; Huntington Disease/metabolism ; Amyotrophic Lateral Sclerosis/metabolism ; }, abstract = {Neurodegenerative diseases (NDDs), mainly including Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), and Alzheimer's disease (AD), are sporadic and rare genetic disorders of the central nervous system. A key feature of these conditions is the slow accumulation of misfolded protein deposits in brain neurons, the excessive aggregation of which leads to neurotoxicity and further disorders of the nervous system.}, } @article {pmid39743032, year = {2025}, author = {Li, Y and Zhang, W and Zhang, Q and Li, Y and Xin, C and Tu, R and Yan, H}, title = {Oxidative stress of mitophagy in neurodegenerative diseases: Mechanism and potential therapeutic targets.}, journal = {Archives of biochemistry and biophysics}, volume = {764}, number = {}, pages = {110283}, doi = {10.1016/j.abb.2024.110283}, pmid = {39743032}, issn = {1096-0384}, mesh = {Humans ; *Mitophagy/drug effects ; *Oxidative Stress/drug effects ; *Neurodegenerative Diseases/metabolism/drug therapy/pathology ; Animals ; Antioxidants/therapeutic use/pharmacology ; Mitochondria/metabolism/pathology ; }, abstract = {Neurodegenerative diseases are now significant chronic progressive neurological conditions that affect individuals' physical health. Oxidative stress is crucial in the development of these diseases. Among the various neurodegenerative diseases, mitochondrial damage has become a major factor in oxidative stress and disease advancement. During this process, oxidative stress and mitophagy plays an important role. In this paper, we introduced the role of mitophagy and oxidative stress in detail, and expounded the relationship between them. In addition, we summarized the pathogenesis of some neurodegenerative diseases and the mechanism of three antioxidants. The former includes AD, PD, HD and ALS, while the latter includes carnosine, adiponectin and resveratrol. Provide goals and directions for further research and treatment of neurodegenerative diseases. This review summarizes the impact of oxidative stress on neurodegenerative diseases by regulating mitophagy, provides a deeper understanding of their pathological mechanisms, and suggests potential new therapeutic targets.}, } @article {pmid39742161, year = {2024}, author = {Mashimo, S and Matsuoka, A and Tanese, K and Kano, O and Ishiko, A}, title = {Idiopathic Multiple Localized Lipoatrophy Mimicking Amyotrophic Lateral Sclerosis.}, journal = {Cureus}, volume = {16}, number = {12}, pages = {e74887}, pmid = {39742161}, issn = {2168-8184}, abstract = {Localized lipoatrophy is a rare condition characterized by the localized loss of subcutaneous adipose tissue. It may occur idiopathically without specific triggers. The pathogenesis of idiopathic localized lipoatrophy remains largely unknown. We present the case of a 53-year-old Japanese woman with multiple localized lipoatrophy who exhibited upper motor neuron signs clinically and panniculitis histologically. She was initially suspected to have amyotrophic lateral sclerosis due to progressive left limb volume loss. Histologically, the lesions showed adipocyte destruction accompanied by predominant plasma infiltration.}, } @article {pmid39741274, year = {2024}, author = {Mandeville, R and Sedghamiz, H and Mansfield, P and Sheean, G and Studer, C and Cordice, D and Ghanbari, G and Malhotra, A and Nemati, S and Koola, J}, title = {Deep learning enhanced transmembranous electromyography in the diagnosis of sleep apnea.}, journal = {BMC neuroscience}, volume = {25}, number = {1}, pages = {80}, pmid = {39741274}, issn = {1471-2202}, support = {R01 HL157985/HL/NHLBI NIH HHS/United States ; T15 LM011271/LM/NLM NIH HHS/United States ; R01 HL166485/HL/NHLBI NIH HHS/United States ; R01 AG063925/AG/NIA NIH HHS/United States ; R01 HL154926/HL/NHLBI NIH HHS/United States ; R01 HL148436/HL/NHLBI NIH HHS/United States ; }, mesh = {Humans ; *Deep Learning ; *Electromyography/methods ; Male ; Middle Aged ; Female ; Adult ; Sleep Apnea, Obstructive/diagnosis/physiopathology ; Polysomnography/methods ; Aged ; Sleep Apnea Syndromes/diagnosis/physiopathology ; }, abstract = {Obstructive sleep apnea (OSA) is widespread, under-recognized, and under-treated, impacting the health and quality of life for millions. The current gold standard for sleep apnea testing is based on the in-lab sleep study, which is costly, cumbersome, not readily available and represents a well-known roadblock to managing this huge societal burden. Assessment of neuromuscular function involved in the upper airway using electromyography (EMG) has shown potential to characterize and diagnose sleep apnea, while the development of transmembranous electromyography (tmEMG), a painless surface probe, has made this opportunity practical and highly feasible. However, experience and ability to interpret electrical signals from the upper airway are scarce, and much of the pertinent information within the signal is likely difficult to detect visually. To overcome this issue, we explored the use of transformers, a deep learning (DL) model architecture with attention mechanisms, to model tmEMG data and distinguish between electromyographic signals from a cohort of control, neurogenic, and sleep apnea patients. Our approach involved three strategies to train a generalizable model on a relatively small dataset including, (1) transfer learning using an audio spectral transformer (AST), (2) the use of 6,000 simulated EMG recordings, converted to spectrograms and using standard backpropagation for fine-tuning, and (3) application of regularization to prevent overfitting and enhance generalizability. This DL approach was tested using 177 transoral EMG recordings from a prior study's database that included six healthy controls, five moderate to severe OSA patients, and five amyotrophic lateral sclerosis (ALS) patients with evidence of bulbar involvement (neurogenic injury). Sensitivity and specificity for classifying neurogenic cases from controls were 98% and 73%, respectively, while classifying OSA from controls were 88% and 64%, respectively. Notably, by averaging the predicted probabilities of each segment for individual patients, the model correctly classified up to 82% of control and OSA patients. These results not only suggest a potential to diagnose OSA patients accurately, but also to identify OSA endotypes that involve neuromuscular pathology, which has major implications for clinical management, patient outcomes, and research.}, } @article {pmid39741002, year = {2024}, author = {Lembo, A and Schiavetti, I and Serafino, M and Caputo, R and Nucci, P}, title = {Comparison of the performance of myopia control in European children and adolescents with defocus incorporated multiple segments (DIMS) and highly aspherical lenslets (HAL) spectacles.}, journal = {BMJ paediatrics open}, volume = {8}, number = {1}, pages = {}, pmid = {39741002}, issn = {2399-9772}, mesh = {Humans ; *Eyeglasses ; Adolescent ; Child ; Male ; Female ; Retrospective Studies ; *Myopia/therapy/epidemiology/physiopathology/prevention & control ; *Refraction, Ocular/physiology ; Disease Progression ; Europe/epidemiology ; Equipment Design ; Visual Acuity/physiology ; }, abstract = {PURPOSE: A performance comparison of two myopia control spectacle lens designs, defocus incorporated multiple segments (DIMS) and highly aspherical lenslets (HAL), at slowing myopia progression in a European child/adolescent population. Previous research directly comparing these designs has been limited to Chinese participants and 1-year follow-up. The prevalence of myopia in European child/adolescent has been estimated at 22.60%.

METHODS: Retrospective cohort study of individuals (6-17 years) with myopia progression. Participants wore DIMS (Hoya MiyoSmart) or HAL (Essilor Stellest) spectacles for a minimum of 2 years. Axial length (AL) and cycloplegic autorefraction (spherical equivalent refraction (SER)) were measured at baseline and 1 and 2 years.

RESULTS: Mean 1-year SER changes for DIMS were -0.34D (±0.46 SD) and HAL -0.30D (±0.30); 2-year changes for DIMS were -0.50D (±0.64 SD) and HAL -0.63D (±0.56). Mean 1-year AL increases for DIMS were 0.19 mm (±0.56) and HAL 0.15 mm (±0.47); 2-year increases for DIMS were 0.29 mm (±0.63) and HAL 0.32 mm (±0.72). For equivalence margins of 0.25D and 0.50D for SER at 1 and 2 years, respectively, and similarly 0.20 mm and 0.30 mm margins for AL, DIMS and HAL lenses were equivalent apart from AL at 1 year where the 0.21 mm 95% CI upper limit just exceeded 0.20 mm. At both 1 and 2 years, none of the differences in mean SERs or ALs between DIMS and HAL were clinically or statistically significant (p≥0.05 Mann-Whitney U test). Using linear mixed model analysis, the interaction between lens type and time did not significantly affect SER or AL at 1- or 2-year follow-up (p≥0.05). 38.4% of children/adolescents with DIMS had no SER progression at 2 years, compared with 21.9% with HAL (p=0.047).

CONCLUSION: In a European population, DIMS and HAL lenses are essentially equivalent in their ability to reduce myopia progression and AL elongation over a 2-year follow-up period.}, } @article {pmid39740768, year = {2025}, author = {Jiang, Y and Fan, W and Li, Y and Xue, H}, title = {Genetic Insights Into the Role of Cathepsins in Alzheimer's Disease, Parkinson's Disease, and Amyotrophic Lateral Sclerosis: Evidence From Mendelian Randomization Study.}, journal = {Brain and behavior}, volume = {15}, number = {1}, pages = {e70207}, pmid = {39740768}, issn = {2162-3279}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics ; *Mendelian Randomization Analysis ; *Alzheimer Disease/genetics ; *Parkinson Disease/genetics ; *Cathepsins/genetics ; *Genome-Wide Association Study ; Cathepsin B/genetics/metabolism ; Cathepsin H/genetics ; Genetic Predisposition to Disease ; Polymorphism, Single Nucleotide ; }, abstract = {BACKGROUND: Previous studies have confirmed the significant role of cathepsins in the development of neurodegenerative diseases. We aimed to determine whether genetically predicted 10 cathepsins may have a causal effect on Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS).

METHODS: We conducted a two-sample bidirectional Mendelian randomization (MR) study using publicly available data from genome-wide association study (GWAS) to assess the causal associations between 10 cathepsins and three neurodegenerative diseases, including AD, PD, and ALS. We employed the following methods, including inverse variance weighting (IVW), MR-Egger, and weighted median (WM). The results were further validated using sensitivity analysis.

RESULTS: The forward MR analysis results indicate that elevated cathepsin H levels increase the risk of AD (p = 0.005, odds ratio [OR] = 1.040, 95% confidence interval [CI] = 1.011-1.069), elevated cathepsin B levels decrease the risk of PD (p < 0.001, OR = 0.890, 95% CI = 0.831-0.954), and no significant association was found between cathepsin levels and ALS. Reverse MR analysis suggests that there is no causal association between 10 cathepsins and three neurodegenerative diseases.

CONCLUSION: Our study provides new genetic insights into the role of cathepsin H in AD and cathepsin B in PD. However, our findings need to be further validated in a wider population, and future research should explore the potential mechanisms of cathepsins in these diseases in order to provide a basis for the development of new therapeutic strategies.}, } @article {pmid39740575, year = {2025}, author = {Fortuna, A and Sorarù, G}, title = {Cervical lower motor neuron syndromes: A diagnostic challenge.}, journal = {Journal of the neurological sciences}, volume = {468}, number = {}, pages = {123357}, doi = {10.1016/j.jns.2024.123357}, pmid = {39740575}, issn = {1878-5883}, mesh = {Humans ; *Motor Neuron Disease/diagnosis/physiopathology/diagnostic imaging ; Magnetic Resonance Imaging/methods ; }, abstract = {Cervical lower motor neuron (LMN) syndromes, also known as brachial paresis, are characterized by muscle atrophy, weakness, and decreased reflexes in the upper limbs, devoid of sensory symptoms. These syndromes can stem from various factors, including degenerative conditions, immune-mediated diseases, infections, toxic exposures, metabolic disorders, and vascular anomalies.[1] Clinical presentations vary, with motor neuron involvement potentially limited to the cervical area or extending to other regions, affecting prognosis. Misdiagnosis is a significant issue, particularly in lower motor neuron presentations, with an error rate nearing 20 %.[2] This review proposes a classification system based on magnetic resonance imaging (MRI) findings, the onset timing of symptoms (acute, subacute, or chronic), the symmetry and distribution of atrophy, and the etiology (sporadic or hereditary). Acute conditions may include spinal ischemia,[3] whereas subacute or chronic forms can manifest as symmetric (e.g., cervical spondylogenic myelopathy)[4] or asymmetric (e.g., Hirayama disease)[5] presentations. Neurophysiological assessments and cervical MRI are crucial for accurate diagnosis, as they reveal patterns that provide lesion localization and additional clues to the underlying cause. A systematic diagnostic approach is essential for navigating the complexities of these syndromes.}, } @article {pmid39739690, year = {2024}, author = {Tian, Y and Heinsinger, N and Hu, Y and Lim, UM and Wang, Y and Fernandis, AZ and Parmentier-Batteur, S and Klein, B and Uslaner, JM and Smith, SM}, title = {Deciphering the interactome of Ataxin-2 and TDP-43 in iPSC-derived neurons for potential ALS targets.}, journal = {PloS one}, volume = {19}, number = {12}, pages = {e0308428}, pmid = {39739690}, issn = {1932-6203}, mesh = {*Induced Pluripotent Stem Cells/metabolism ; *Ataxin-2/metabolism/genetics ; Humans ; *Amyotrophic Lateral Sclerosis/metabolism/pathology ; *Neurons/metabolism ; *DNA-Binding Proteins/metabolism/genetics ; Protein Binding ; }, abstract = {Ataxin-2 is a protein containing a polyQ extension and intermediate length of polyQ extensions increases the risk of Amyotrophic Lateral Sclerosis (ALS). Down-regulation of Ataxin-2 has been shown to mitigate TDP-43 proteinopathy in ALS models. To identify alternative therapeutic targets that can mitigate TDP-43 toxicity, we examined the interaction between Ataxin-2 and TDP-43. Co-immunoprecipitation demonstrated that Ataxin-2 and TDP-43 interact, that their interaction is mediated through the RNA recognition motif (RRM) of TDP-43, and knocking down Ataxin-2 or mutating the RRM domains rescued TDP-43 toxicity in an iPSC-derived neuronal model with TDP-43 overexpression. To decipher the Ataxin-2 and TDP-43 interactome, we used co-immunoprecipitation followed by mass spectrometry to identify proteins that interacted with Ataxin-2 and TDP-43 under conditions of endogenous or overexpressed TDP-43 in iPSC-derived neurons. Multiple interactome proteins were differentially regulated by TDP-43 overexpression and toxicity, including those involved in RNA regulation, cell survival, cytoskeleton reorganization, protein modification, and diseases. Interestingly, the RNA-binding protein (RBP), TAF15 which has been implicated in ALS was identified as a strong binder of Ataxin-2 in the condition of TDP-43 overexpression. Together, this study provides a comprehensive annotation of the Ataxin-2 and TDP-43 interactome and identifies potential therapeutic pathways and targets that could be modulated to alleviate Ataxin-2 and TDP-43 interaction-induced toxicity in ALS.}, } @article {pmid39739500, year = {2025}, author = {Saiduzzaman, M and Roy, S and Bhattacharjee, M}, title = {Young Patient with Amyotrophic Lateral Sclerosis Following Suicidal Organophosphorus Compounds Poisoning: A Case Report.}, journal = {Mymensingh medical journal : MMJ}, volume = {34}, number = {1}, pages = {272-275}, pmid = {39739500}, issn = {2408-8757}, mesh = {Humans ; Male ; *Amyotrophic Lateral Sclerosis/therapy/complications ; *Organophosphate Poisoning/complications/therapy/etiology ; Suicide, Attempted ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease involving both upper and lower motor neurons. Its underlying etiology is not well established. But certain risk factors including genetic predilection and exposure to certain environmental toxins like Organophosphorus Compounds (OPC) have been postulated. Here we describe a young male patient presented with progressive weakness of all four limbs immediately following survival from OPC ingestion as a suicidal attempt. He also had slurred, indistinct speech without swallowing difficulty and sensory findings. Neurological examination findings are having mixed upper and lower motor neuron signs. EMG (Electromyography) shows features of denervation and reinnervation suggestive of ALS. ALS following single exposure to OPC is a relatively rare finding. Supportive treatments including physiotherapy and psychotherapy were given. This case may strengthen the etiological link between OPC and ALS.}, } @article {pmid39739450, year = {2025}, author = {Aiello, EN and Poletti, B and Consonni, M and Iazzolino, B and Torre, S and Faltracco, V and Telesca, A and Palumbo, F and Curti, B and De Luca, G and Bella, ED and Bersano, E and Riva, N and Verde, F and Messina, S and Doretti, A and Maranzano, A and Morelli, C and Calvo, A and Silani, V and Lauria, G and Chiò, A and Ticozzi, N}, title = {Education moderates the association between motor involvement and executive status in ALS.}, journal = {European journal of neurology}, volume = {32}, number = {1}, pages = {e70027}, pmid = {39739450}, issn = {1468-1331}, support = {//BIBLIOSAN/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/psychology/complications/physiopathology ; Male ; Female ; *Executive Function/physiology ; Middle Aged ; *Educational Status ; Aged ; *Cognitive Reserve/physiology ; Neuropsychological Tests ; Cohort Studies ; }, abstract = {BACKGROUND: This study aimed to determine whether educational attainment-a common proxy of cognitive reserve (CR)-influences the association between motor and cognitive/behavioural outcomes in a large cohort of ALS patients without dementia.

METHODS: N = 726 ALS patients without FTD were assessed for motor (ALSFRS-R), cognitive (Edinburgh Cognitive and Behavioural ALS Screen, ECAS) and behavioural outcomes (ECAS-Carer Interview, ECAS-CI). CR was operationalized via educational attainment (in years). Moderation models were run on each subscale of the cognitive section of the ECAS and on the ECAS-CI by addressing ALSFRS-R as the predictor and education as the moderator.

RESULTS: Education was associated with both the ALSFRS-R and all the cognitive subscales of the ECAS, while not with the ECAS-CI. As to moderation models, a significant Education*ALSFRS-R interaction was detected solely with regard to the ECAS-Executive-with its simple slope-based decomposition revealing that higher ALSFRS-R scores were associated with higher scores on the ECAS-Executive for patients with low (p < 0.001) and average (p = 0.007), while not high, levels of education.

DISCUSSION: Education seems to moderate the association between motor involvement and executive status in ALS patients without dementia, thus possibly exerting a protective role towards both motor function and cognition in this population.}, } @article {pmid39738171, year = {2024}, author = {Jeon, P and Ham, HJ and Choi, H and Park, S and Jang, JW and Park, SW and Cho, DH and Lee, HJ and Song, HK and Komatsu, M and Han, D and Jang, DJ and Lee, JA}, title = {NS1 binding protein regulates stress granule dynamics and clearance by inhibiting p62 ubiquitination.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {10925}, pmid = {39738171}, issn = {2041-1723}, support = {2020M3E5D9079911//National Research Foundation of Korea (NRF)/ ; 2023R1A2C2008092//National Research Foundation of Korea (NRF)/ ; 2023R1A2C2008092//National Research Foundation of Korea (NRF)/ ; RS-2023-00218515//National Research Foundation of Korea (NRF)/ ; JP19H05706//MEXT | Japan Society for the Promotion of Science (JSPS)/ ; JP21H004771//MEXT | Japan Society for the Promotion of Science (JSPS)/ ; 23K20044//MEXT | Japan Society for the Promotion of Science (JSPS)/ ; 24H00060//MEXT | Japan Society for the Promotion of Science (JSPS)/ ; JP22gm1410004h0003//Japan Agency for Medical Research and Development (AMED)/ ; }, mesh = {Humans ; *Ubiquitination ; *Amyotrophic Lateral Sclerosis/metabolism/pathology/genetics ; *Stress Granules/metabolism ; *Adaptor Proteins, Signal Transducing/metabolism/genetics ; *Sequestosome-1 Protein/metabolism/genetics ; Microtubule-Associated Proteins/metabolism/genetics ; Neurons/metabolism ; HEK293 Cells ; Oxidative Stress ; HeLa Cells ; Autophagy ; Viral Nonstructural Proteins/metabolism/genetics ; Protein Binding ; Cytoplasmic Granules/metabolism ; Apoptosis Regulatory Proteins ; }, abstract = {The NS1 binding protein, known for interacting with the influenza A virus protein, is involved in RNA processing, cancer, and nerve cell growth regulation. However, its role in stress response independent of viral infections remains unclear. This study investigates NS1 binding protein's function in regulating stress granules during oxidative stress through interactions with GABARAP subfamily proteins. We find that NS1 binding protein localizes to stress granules, interacting with core components, GABARAP proteins, and p62, a protein involved in autophagy. In cells lacking NS1 binding protein, stress granule dynamics are altered, and p62 ubiquitination is increased, suggesting impaired stress granule degradation. Overexpression of NS1 binding protein reduces p62 ubiquitination. In amyotrophic lateral sclerosis patient-derived neurons, reduced NS1 binding protein and p62 disrupt stress granule morphology. These findings identify NS1 binding protein as a negative regulator of p62 ubiquitination and a facilitator of GABARAP recruitment to stress granules, implicating it in stress granule regulation and amyotrophic lateral sclerosis pathogenesis.}, } @article {pmid39737952, year = {2024}, author = {Alecki, C and Rizwan, J and Le, P and Jacob-Tomas, S and Comaduran, MF and Verbrugghe, M and Xu, JMS and Minotti, S and Lynch, J and Biswas, J and Wu, T and Durham, HD and Yeo, GW and Vera, M}, title = {Localized molecular chaperone synthesis maintains neuronal dendrite proteostasis.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {10796}, pmid = {39737952}, issn = {2041-1723}, support = {RF1 MH126719/MH/NIMH NIH HHS/United States ; 300232//Fonds de Recherche du Québec - Santé (Fonds de la recherche en sante du Quebec)/ ; MH126719//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; HG009889//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; U24 HG009889/HG/NHGRI NIH HHS/United States ; R01 HG004659/HG/NHGRI NIH HHS/United States ; HG011864//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; PJT-186141//Gouvernement du Canada | Canadian Institutes of Health Research (Instituts de Recherche en Santé du Canada)/ ; HG004659//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; Hudson Translational Team Grant//ALS Society of Canada (ALS Canada)/ ; R01 HG011864/HG/NHGRI NIH HHS/United States ; R01 NS103172/NS/NINDS NIH HHS/United States ; 2022-ALS Discovery Grant//ALS Society of Canada (ALS Canada)/ ; P30 CA008748/CA/NCI NIH HHS/United States ; U41 HG009889/HG/NHGRI NIH HHS/United States ; }, mesh = {*Dendrites/metabolism ; *Proteostasis ; Animals ; Humans ; Mice ; *RNA-Binding Protein FUS/metabolism/genetics ; *RNA, Messenger/metabolism/genetics ; *Motor Neurons/metabolism ; *HSC70 Heat-Shock Proteins/metabolism/genetics ; *Hippocampus/metabolism/cytology ; Spinal Cord/metabolism ; Induced Pluripotent Stem Cells/metabolism ; Protein Biosynthesis ; Molecular Chaperones/metabolism/genetics ; HSP70 Heat-Shock Proteins/metabolism/genetics ; Microtubules/metabolism ; }, abstract = {Proteostasis is maintained through regulated protein synthesis and degradation and chaperone-assisted protein folding. However, this is challenging in neuronal projections because of their polarized morphology and constant synaptic proteome remodeling. Using high-resolution fluorescence microscopy, we discover that hippocampal and spinal cord motor neurons of mouse and human origin localize a subset of chaperone mRNAs to their dendrites and use microtubule-based transport to increase this asymmetric localization following proteotoxic stress. The most abundant dendritic chaperone mRNA encodes a constitutive heat shock protein 70 family member (HSPA8). Proteotoxic stress also enhances HSPA8 mRNA translation efficiency in dendrites. Stress-mediated HSPA8 mRNA localization to the dendrites is impaired by depleting fused in sarcoma-an amyotrophic lateral sclerosis-related protein-in cultured spinal cord mouse motor neurons or by expressing a pathogenic variant of heterogenous nuclear ribonucleoprotein A2/B1 in neurons derived from human induced pluripotent stem cells. These results reveal a neuronal stress response in which RNA-binding proteins increase the dendritic localization of HSPA8 mRNA to maintain proteostasis and prevent neurodegeneration.}, } @article {pmid39737769, year = {2025}, author = {Akyuz, E and Aslan, FS and Hekimoglu, A and Yilmaz, BN}, title = {Insights Into Retinal Pathologies in Neurological Disorders: A Focus on Parkinson's Disease, Multiple Sclerosis, Amyotrophic Lateral Sclerosis, and Alzheimer's Disease.}, journal = {Journal of neuroscience research}, volume = {103}, number = {1}, pages = {e70006}, doi = {10.1002/jnr.70006}, pmid = {39737769}, issn = {1097-4547}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/pathology ; *Parkinson Disease/diagnosis/diagnostic imaging/pathology ; *Multiple Sclerosis/pathology/diagnosis/diagnostic imaging ; *Alzheimer Disease/pathology/diagnosis ; *Retina/pathology/diagnostic imaging ; Tomography, Optical Coherence/methods ; Retinal Diseases/diagnosis/pathology/etiology ; Animals ; }, abstract = {Neurological diseases are central nervous system (CNS) disorders affecting the whole body. Early diagnosis of the diseases is difficult due to the lack of disease-specific tests. Adding new biomarkers external to the CNS facilitates the diagnosis of neurological diseases. In this respect, the retina has a common embryologic origin with the CNS. Retinal imaging technologies including optical coherence tomography (OCT) can be used in the understanding and processual monitoring of neurological diseases. Retinal imaging has been recently recognized as a potential source of biomarkers for neurological diseases, increasing the number of studies in this direction. In this review, the association of retinal abnormalities with Parkinson's disease (PD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), and Alzheimer's disease (AD) is explained. Structural and functional abnormalities in retina as a predictive marker may facilitate early diagnosis of diseases. Although not all retinal abnormalities are predictive of neurologic diseases, changes in the retinal layers including retinal pigment epithelium and plexiform layers should suggest the risk of PD, MS, ALS, and AD.}, } @article {pmid39737526, year = {2025}, author = {Nakaya, T}, title = {Release of FUS into the extracellular space is regulated by its amino-terminal prion-like domain.}, journal = {FEBS letters}, volume = {599}, number = {7}, pages = {1046-1054}, doi = {10.1002/1873-3468.15086}, pmid = {39737526}, issn = {1873-3468}, support = {22K07374//Japan Society for the Promotion of Science/ ; }, mesh = {*RNA-Binding Protein FUS/metabolism/chemistry/genetics ; Animals ; Humans ; Mice ; Protein Domains ; *Extracellular Space/metabolism ; *Neurons/metabolism ; *Prions/metabolism/chemistry ; Amyotrophic Lateral Sclerosis/metabolism ; }, abstract = {Fused in sarcoma (FUS) is a causative factor of amyotrophic lateral sclerosis (ALS) and is believed to propagate pathologically by transmission from cell to cell. However, the mechanism underlying FUS release from cells, which is a critical step for the propagation system, remains poorly understood. This study conducted an analysis of the release of human and mouse FUS from neurons, revealing that human FUS is significantly released into the media compared to its mouse counterpart. Further study using chimeric FUS proteins identified the amino-terminal region of human FUS as essential for its release. These findings indicate that human FUS is released directly from neurons and underscore the novel functional role of its amino-terminal region in this process.}, } @article {pmid39736981, year = {2024}, author = {Zhang, Y and Li, N and Ge, Z and Li, F}, title = {Blood component therapy for dry eye disease: a systematic review and network meta-analysis.}, journal = {Frontiers in medicine}, volume = {11}, number = {}, pages = {1500160}, pmid = {39736981}, issn = {2296-858X}, abstract = {OBJECTIVE: Blood component therapy has shown promising potential as an emerging treatment for dry eye disease; however, it remains unclear which specific blood component is the most effective. This study aims to compare the efficacy of different blood components in the treatment of dry eye disease through a network meta-analysis, with the goal of providing the latest and most reliable evidence for clinical practice.

METHODS: We conducted a systematic search of the PubMed, Web of Science, Cochrane, Embase, and Scopus databases, with the search concluding on June 1, 2024. Two independent researchers performed literature screening, data extraction, and quality assessment.

RESULTS: A total of 16 randomized controlled trials (RCTs) involving 898 patients with dry eye disease were included. Six different blood components were utilized in treating dry eye disease, with platelet-rich plasma (PRP) being the most widely used. The results of the network meta-analysis indicated that platelet-rich plasma eye drops (PRPD) significantly outperformed artificial tears (AT) in improving the corneal fluorescein staining score (CFSS), while autologous serum (ALS) and umbilical cord serum (UCS) also demonstrated significantly better effects than AT in enhancing tear break-up time (TBUT). Additionally, ALS, PRP injection (PRPI), and PRPD showed significantly superior outcomes compared to AT in improving the ocular surface disease index (OSDI). However, no statistically significant differences were found among the various treatment modalities regarding their effects on Schirmer's I value, CFSS, TBUT, and OSDI. SUCRA analysis predicted that UCS was the most effective in improving Schirmer's I value and TBUT, while PRP excelled in enhancing CFSS and OSDI. Limitations such as publication bias and issues related to randomization, allocation concealment, and blinding may affect the reliability of the current findings.

CONCLUSION: Blood component therapy can significantly improve the pathological damage and ocular surface health in patients with dry eye disease. For those with aqueous-deficient dry eye, UCS may represent the optimal treatment option. In contrast, for patients with more severe corneal epithelial damage, PRP may offer a more effective therapeutic approach.

https://www.crd.york.ac.uk/PROSPERO/, CRD42024534091.}, } @article {pmid39736783, year = {2024}, author = {Zeng, J and Luo, C and Jiang, Y and Hu, T and Lin, B and Xie, Y and Lan, J and Miao, J}, title = {Decoding TDP-43: the molecular chameleon of neurodegenerative diseases.}, journal = {Acta neuropathologica communications}, volume = {12}, number = {1}, pages = {205}, pmid = {39736783}, issn = {2051-5960}, support = {YNXM2024062//High-quality development project of public hospitals in Baoan District, Shenzhen/ ; YNXM2024015//High-quality development project of public hospitals in Baoan District, Shenzhen/ ; }, mesh = {Humans ; *DNA-Binding Proteins/metabolism/genetics ; *Neurodegenerative Diseases/metabolism/genetics/pathology ; Animals ; }, abstract = {TAR DNA-binding protein 43 (TDP-43) has emerged as a critical player in neurodegenerative disorders, with its dysfunction implicated in a wide spectrum of diseases including amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration (FTLD), and Alzheimer's disease (AD). This comprehensive review explores the multifaceted roles of TDP-43 in both physiological and pathological contexts. We delve into TDP-43's crucial functions in RNA metabolism, including splicing regulation, mRNA stability, and miRNA biogenesis. Particular emphasis is placed on recent discoveries regarding TDP-43's involvement in DNA interactions and chromatin dynamics, highlighting its broader impact on gene expression and genome stability. The review also examines the complex pathogenesis of TDP-43-related disorders, discussing the protein's propensity for aggregation, its effects on mitochondrial function, and its non-cell autonomous impacts on glial cells. We provide an in-depth analysis of TDP-43 pathology across various neurodegenerative conditions, from well-established associations in ALS and FTLD to emerging roles in diseases such as Huntington's disease and Niemann-Pick C disease. The potential of TDP-43 as a therapeutic target is explored, with a focus on recent developments in targeting cryptic exon inclusion and other TDP-43-mediated processes. This review synthesizes current knowledge on TDP-43 biology and pathology, offering insights into the protein's central role in neurodegeneration and highlighting promising avenues for future research and therapeutic interventions.}, } @article {pmid39735276, year = {2024}, author = {Moyana, TN}, title = {Small cell lung carcinoma metastatic to the stomach: Commonly overlooked, limited treatment options.}, journal = {World journal of gastroenterology}, volume = {30}, number = {48}, pages = {5198-5204}, pmid = {39735276}, issn = {2219-2840}, mesh = {Humans ; *Small Cell Lung Carcinoma/therapy/secondary/pathology/diagnostic imaging ; *Stomach Neoplasms/pathology/therapy/diagnostic imaging ; *Lung Neoplasms/secondary/therapy/pathology/diagnostic imaging ; Prognosis ; Biomarkers, Tumor/analysis/metabolism ; Positron Emission Tomography Computed Tomography/methods ; Immune Checkpoint Inhibitors/therapeutic use ; Immunohistochemistry ; }, abstract = {Small cell lung carcinoma metastatic to the stomach, whether synchronous or metachronous, is a rare phenomenon accounting for < 0.5% of lung cancers. Hence it can be overlooked by clinicians resulting in delayed diagnosis. This manuscript comments on Yang et al's article which reported 3 such cases. The main diagnostic features are based on routine morphology comprised of small cells with hyperchromatic nuclei, scant cytoplasm, brisk mitoses and necrosis. This can be supplemented by immunohistochemistry demonstrating positivity for cytokeratin, thyroid transcription factor-1 and neuroendocrine markers as well as a high Ki-67 labelling index. Imaging modalities such as positron emission tomography/contrast computed tomography help to confirm lung origin and rule out the possibility of extra-pulmonary small cell carcinoma. The predominant mechanism of spread is most likely hematogeneous. Prognosis is generally poor since this represents stage 4 disease but survival can be improved by chemo/radiotherapy and palliative surgery in select cases. Though outcomes have not changed much in the last several decades, the recent Food and Drug Administration approval of immune checkpoint inhibitors was a significant milestone as was the delineation of small cell lung carcinoma molecular subtypes. Liquid biopsies are increasingly being used for biomarker studies in clinical trials to assess treatment response and prognosis.}, } @article {pmid39735081, year = {2024}, author = {Dost, W and Rasully, MQ and Zaman, MN and Dost, W and Ali, W and Ayobi, SA and Dost, R and Niazi, J and Bakht, K and Iqbal, A and Bokhari, SFH}, title = {Predictive Biomarkers for the Early Detection of Anastomotic Leaks in Colorectal Surgeries: A Systematic Review.}, journal = {Cureus}, volume = {16}, number = {11}, pages = {e74616}, pmid = {39735081}, issn = {2168-8184}, abstract = {Anastomotic leaks (ALs) remain a serious postoperative complication in colorectal surgery, often resulting in significant morbidity, prolonged hospitalization, and increased mortality risk. This systematic review aims to evaluate the role of predictive biomarkers in the early detection of ALs, focusing on their diagnostic accuracy and clinical utility. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a comprehensive literature search was conducted across MEDLINE, Scopus, CENTRAL, and Web of Science, identifying studies that examined biomarkers such as C-reactive protein (CRP), procalcitonin (PCT), and white blood cell (WBC) count in the context of AL. A total of 20 studies met the inclusion criteria, with sample sizes ranging from 59 to 2,655 patients undergoing colorectal surgeries with primary anastomosis. CRP emerged as the most widely studied and reliable biomarker, with studies suggesting that elevated CRP levels, particularly on postoperative days 3-4, can effectively indicate AL risk, showing high negative predictive value. PCT has also shown promise as a complementary biomarker, offering enhanced specificity for infectious complications. Although WBC count alone was a limited predictor, it may add diagnostic value when used with other markers. In addition, innovative biomarkers, such as inflammatory indices in peritoneal fluid, demonstrated potential for further improving AL detection accuracy.}, } @article {pmid39731449, year = {2025}, author = {Fabbrizio, P and Baindoor, S and Margotta, C and Su, J and Morrissey, EP and Woods, I and Hogg, MC and Vianello, S and Venø, MT and Kjems, J and Sorarù, G and Bendotti, C and Prehn, JHM and Nardo, G}, title = {Protective role of Angiogenin in muscle regeneration in amyotrophic lateral sclerosis: Diagnostic and therapeutic implications.}, journal = {Brain pathology (Zurich, Switzerland)}, volume = {35}, number = {4}, pages = {e13328}, pmid = {39731449}, issn = {1750-3639}, support = {CUP E48I20000000007//Regione Lombardia/ ; //EU Joint Programme-Neurodegenerative Disease Research/ ; SG-2018-12366226//Ministero della Salute, Italy/ ; MUSALS-AChR//Agenzia di Ricerca per la Sclerosi Laterale Amiotrofica/ ; 18/CRT/6214//Science Foundation Ireland CRT in Genomics Data Science/ ; 17/JPND/3455/SFI_/Science Foundation Ireland/Ireland ; 20/SP/8953/SFI_/Science Foundation Ireland/Ireland ; 21/RC/10294_P2/SFI_/Science Foundation Ireland/Ireland ; }, mesh = {*Amyotrophic Lateral Sclerosis/metabolism/pathology/physiopathology/diagnosis ; *Ribonuclease, Pancreatic/metabolism ; Animals ; Humans ; *Muscle, Skeletal/metabolism/pathology ; Mice ; *Regeneration/physiology ; Mice, Transgenic ; Male ; Female ; Disease Models, Animal ; Middle Aged ; Aged ; Muscle Development/physiology ; Mice, Inbred C57BL ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neuromuscular disease with no effective treatments, in part caused by variations in progression and the absence of biomarkers. Mice carrying the SOD1G93A transgene with different genetic backgrounds show variable disease rates, reflecting the diversity of patients. While extensive research has been done on the involvement of the central nervous system, the role of skeletal muscle remains underexplored. We examined the impact of angiogenin, including its RNase activity, in skeletal muscles of ALS mouse models and in biopsies from ALS patients. Elevated levels of angiogenin were found in slowly progressing mice but not in rapidly progressing mice, correlating with increased muscle regeneration and vascularisation. In patients, higher levels of angiogenin in skeletal muscles correlated with milder disease. Mechanistically, angiogenin promotes muscle regeneration and vascularisation through satellite cell-endothelial interactions during myogenesis and angiogenesis. Furthermore, specific angiogenin-derived tiRNAs were upregulated in slowly progressing mice, suggesting their role in mediating the effects of angiogenin. These findings highlight angiogenin and its tiRNAs as potential prognostic markers and therapeutic targets for ALS, offering avenues for patient stratification and interventions to mitigate disease progression by promoting muscle regeneration.}, } @article {pmid39731185, year = {2024}, author = {Itou, T and Fujita, K and Okuzono, Y and Warude, D and Miyakawa, S and Mihara, Y and Matsui, N and Morino, H and Kikukawa, Y and Izumi, Y}, title = {Th17 and effector CD8 T cells relate to disease progression in amyotrophic lateral sclerosis: a case control study.}, journal = {Journal of neuroinflammation}, volume = {21}, number = {1}, pages = {331}, pmid = {39731185}, issn = {1742-2094}, support = {NA//Takeda Pharmaceutical Company/ ; JPMH23FC1008//Ministry of Health, Labour and Welfare/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/immunology/pathology ; Humans ; *Disease Progression ; Female ; *CD8-Positive T-Lymphocytes/immunology ; Middle Aged ; Male ; *Th17 Cells/immunology/metabolism ; Case-Control Studies ; Aged ; Adult ; }, abstract = {The immune system has garnered attention due to its association with disease progression in amyotrophic lateral sclerosis (ALS). However, the role of peripheral immune cells in this context remains controversial. Here, we conducted single-cell RNA-sequencing of peripheral blood mononuclear cells to comprehensively profile immune cells concerning the rate of disease progression in patients with ALS. Our analysis revealed increased frequencies of T helper 17 cells (Th17) relative to regulatory T cells, effector CD8 T cells relative to naïve CD8 T cells, and CD16[high]CD56[low] mature natural killer cells relative to CD16[low]CD56[high] naïve natural killer cells in patients with rapidly progressive ALS. Additionally, we employed serum proteomics through a proximity extension assay combined with next-generation sequencing to identify inflammation-related proteins associated with rapid disease progression. Among these proteins, interleukin-17 A correlated with the frequency of Th17, while killer cell lectin-like receptor D1 (CD94) correlated with the frequency of effector CD8 T cells. These findings further support the active roles played by these specific immune cell types in the progression of ALS.}, } @article {pmid39730482, year = {2024}, author = {Mitsi, E and Votsi, C and Koutsou, P and Georghiou, A and Christodoulou, CC and Kleopa, K and Zamba-Papanicolaou, E and Christodoulou, K and Nicolaou, P}, title = {Genetic epidemiology of amyotrophic lateral sclerosis in Cyprus: a population-based study.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {30781}, pmid = {39730482}, issn = {2045-2322}, support = {73234//Telethon Cyprus/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/epidemiology ; Male ; Cyprus/epidemiology ; Female ; Middle Aged ; Aged ; *C9orf72 Protein/genetics ; Superoxide Dismutase-1/genetics ; Genetic Predisposition to Disease ; Molecular Epidemiology ; DNA-Binding Proteins/genetics ; Adult ; RNA-Binding Protein FUS/genetics ; High-Throughput Nucleotide Sequencing ; Mutation ; Cohort Studies ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a devastating, uniformly lethal degenerative disease of motor neurons, presenting with relentlessly progressive muscle atrophy and weakness. More than fifty genes carrying causative or disease-modifying variants have been identified since the 1990s, when the first ALS-associated variant in the gene SOD1 was discovered. The most commonly mutated ALS genes in the European populations include the C9orf72, SOD1, TARDBP and FUS. Understanding the genetic causes of ALS within a population is becoming more significant, especially in light of the possible development of personalized medicine. Here, we provide clinical and genetic data on familial and sporadic ALS patients in a Greek-Cypriot population-based cohort. Eighty-nine ALS patients, including 21 familial ALS (fALS) (23.6%) and 68 sporadic ALS (sALS) (76.4%), provided the cohort for variant screening of the most common ALS-associated genes. Moreover, next-generation sequencing (NGS) was also performed to identify rare ALS variants, and in silico prediction tools were applied to predict the downstream effect of the variants detected in our study. The pathogenic hexanucleotide G4C2 repeat expansion in C9orf72 was the predominant genetic cause (22.47%) of ALS in our population, while variants in six additional ALS-associated genes were identified, including ALS2, TARDBP, FIG4, TBK1, GLT8D1, and BICD2.}, } @article {pmid39729643, year = {2024}, author = {Meiling, JB and Caress, JB and Cartwright, MS}, title = {Ultra High-Frequency Ultrasound of Median Nerve Fascicles at the Wrist in Amyotrophic Lateral Sclerosis: An Exploratory Study.}, journal = {Journal of clinical neurophysiology : official publication of the American Electroencephalographic Society}, volume = {42}, number = {5}, pages = {466-469}, doi = {10.1097/WNP.0000000000001136}, pmid = {39729643}, issn = {1537-1603}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnostic imaging/physiopathology ; Male ; *Median Nerve/diagnostic imaging ; Female ; Middle Aged ; Ultrasonography/methods ; *Wrist/diagnostic imaging/innervation ; Aged ; Adult ; }, abstract = {PURPOSE: High-frequency ultrasound (HFUS) of muscle and nerve has the potential to be a reliable, responsive, and informative biomarker of disease progression for individuals with amyotrophic lateral sclerosis (ALS). High-frequency ultrasound is not able to visualize median nerve fascicles to the same extent as ultra-high-frequency ultrasound (UHFUS). Evaluating the number and size of fascicles within a nerve may facilitate a better understanding of nerve diseases. This exploratory study aims to image median nerve fascicles at the wrist in individuals with ALS using UHFUS and compare these findings with those from previously observed controls.

METHODS: Fifteen individuals with ALS underwent sonographic examination of the median nerves on each upper limb using UHFUS with a 48-MHz linear array transducer. Fascicle count and density in each examined nerve were determined by a single rater. Demographic and sonographic data from 20 previously studied controls were compared.

RESULTS: In individuals with ALS, the average fascicle number was 22.4 (SD 5.2) and average fascicle density 1.7 (SD 0.5). There was no significant difference in fascicle counts between individuals with ALS and controls.

CONCLUSIONS: Fascicular quantification using UHFUS is possible in individuals with ALS. Given the lack of appreciable difference between fascicle counts in individuals with ALS and controls, UHFUS of the median nerve at the wrist may not be a responsive biomarker for ALS disease progression.}, } @article {pmid39728809, year = {2024}, author = {Al Haffar, M and Fajloun, Z and Azar, S and Sabatier, JM and Abi Khattar, Z}, title = {Lesser-Known Cyanotoxins: A Comprehensive Review of Their Health and Environmental Impacts.}, journal = {Toxins}, volume = {16}, number = {12}, pages = {}, pmid = {39728809}, issn = {2072-6651}, mesh = {Humans ; *Cyanobacteria/metabolism ; *Bacterial Toxins/toxicity ; Animals ; Harmful Algal Bloom ; Cyanobacteria Toxins ; Microcystins/toxicity ; }, abstract = {Cyanobacteria, also known as blue-green algae, are a diverse phylum of photosynthetic, Gram-negative bacteria and one of the largest microbial taxa. These organisms produce cyanotoxins, which are secondary metabolites that can have significant impacts on both human health and the environment. While toxins like Microcystins and Cylindrospermopsins are well-documented and have been extensively studied, other cyanotoxins, including those produced by Lyngbya and Nostoc, remain underexplored. These lesser-known toxins can cause various health issues in humans, including neurotoxicity, hepatotoxicity, and dermatotoxicity, each through distinct mechanisms. Moreover, recent studies have shown that cyanobacteria can be aerosolized and transmitted through the air over long distances, providing an additional route for human exposure to their harmful effects. However, it remains an area that requires much more investigation to accurately assess the health risks and develop appropriate public health guidelines. In addition to direct exposure to toxins, cyanobacteria can lead to harmful algal blooms, which pose further risks to human and wildlife health, and are a global concern. There is limited knowledge about these lesser-known cyanotoxins, highlighting the need for further research to understand their clinical manifestations and improve society's preparedness for the associated health risks. This work aims to review the existing literature on these underexplored cyanotoxins, which are associated with human intoxication, elucidate their clinical relevance, address significant challenges in cyanobacterial research, and provide guidance on mitigating their adverse effects.}, } @article {pmid39728753, year = {2024}, author = {Boziki, M and Theotokis, P and Kesidou, E and Nella, M and Bakirtzis, C and Karafoulidou, E and Tzitiridou-Chatzopoulou, M and Doulberis, M and Kazakos, E and Deretzi, G and Grigoriadis, N and Kountouras, J}, title = {Impact of Mast Cell Activation on Neurodegeneration: A Potential Role for Gut-Brain Axis and Helicobacter pylori Infection.}, journal = {Neurology international}, volume = {16}, number = {6}, pages = {1750-1778}, pmid = {39728753}, issn = {2035-8385}, abstract = {BACKGROUND: The innate immune response aims to prevent pathogens from entering the organism and/or to facilitate pathogen clearance. Innate immune cells, such as macrophages, mast cells (MCs), natural killer cells and neutrophils, bear pattern recognition receptors and are thus able to recognize common molecular patterns, such as pathogen-associated molecular patterns (PAMPs), and damage-associated molecular patterns (DAMPs), the later occurring in the context of neuroinflammation. An inflammatory component in the pathology of otherwise "primary cerebrovascular and neurodegenerative" disease has recently been recognized and targeted as a means of therapeutic intervention. Activated MCs are multifunctional effector cells generated from hematopoietic stem cells that, together with dendritic cells, represent first-line immune defense mechanisms against pathogens and/or tissue destruction.

METHODS: This review aims to summarize evidence of MC implication in the pathogenesis of neurodegenerative diseases, namely, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease, and multiple sclerosis.

RESULTS: In view of recent evidence that the gut-brain axis may be implicated in the pathogenesis of neurodegenerative diseases and the characterization of the neuroinflammatory component in the pathology of these diseases, this review also focuses on MCs as potential mediators in the gut-brain axis bi-directional communication and the possible role of Helicobacter pylori, a gastric pathogen known to alter the gut-brain axis homeostasis towards local and systemic pro-inflammatory responses.

CONCLUSION: As MCs and Helicobacter pylori infection may offer targets of intervention with potential therapeutic implications for neurodegenerative disease, more clinical and translational evidence is needed to elucidate this field.}, } @article {pmid39728018, year = {2024}, author = {Jeyarajan, S and Ranjith, S and Veerapandian, R and Natarajaseenivasan, K and Chidambaram, P and Kumarasamy, A}, title = {Antibiofilm Activity of Epinecidin-1 and Its Variants Against Drug-Resistant Candida krusei and Candida tropicalis Isolates from Vaginal Candidiasis Patients.}, journal = {Infectious disease reports}, volume = {16}, number = {6}, pages = {1214-1229}, pmid = {39728018}, issn = {2036-7430}, support = {BT/PR2071/BBE/117/241/2016//Department of Biotechnology, India/ ; 311/RUSA(2.0)/2018//RUSA 2.0 Biological Sciences/ ; 01706/P6/2021//Tamil Nadu State Council for Higher Education (TANSCHE)/ ; ICMR-NET- 61754/2010//Indian Council of Medical Research/ ; }, abstract = {Background/Objective: Indwelling intrauterine contraceptive devices (IUDs) have surfaces that facilitate the attachment of Candida spp., creating a suitable environment for biofilm formation. Due to this, vulvovaginal candidiasis (VVC) is frequently linked to IUD usage, necessitating the prompt removal of these devices for effective treatment. In this study, we evaluated the susceptibility of antimicrobial peptides in vitro against biofilm forming, Amphotericin B (MIC50 > 2 mg L[-1]) resistant Candida krusei and Candida tropicalis isolated from IUD users who had signs of vaginal candidiasis (hemorrhage, pelvic pain, inflammation, itching, and vaginal discharge). Three antimicrobial peptides, namely, epinecidin-1 (epi-1) and its two variants, namely, variant-1 (Var-1) and variant-2 (Var-2), which were reported to have enhanced antibacterial activity were tested against IUD isolates (C. krusei and C. tropicalis) with pathogenic form of Candida albicans as control. Variants of epi-1, namely, Var-1 and Var-2 were created by substituting lysine in the place of histidine and alanine. Methods: The antimicrobial activity was measured using the microbroth dilution method to determine the minimum inhibitory concentration (MIC) of peptides against C. albicans, C. krusei and C. tropicalis. The MIC of each peptide was used for biofilm assay by Crystal violet staining, Scanning Electron Microscopy, and Reactive Oxygen Species (ROS) assay. To find the possible mechanism of anti-biofilm activity by the peptides, their ability to interact with Candida spp. cell membrane proteins such as Exo-β-(1,3)-Glucanase, Secreted Aspartic Proteinase (Sap) 1, and N-terminal Domain Adhesin: Als 9-2 were determined through PatchDock. Results: The MIC values of peptides: epi-1, var-1 and var-2 against C. albicans are 128 μg mL[-1], 64 μg mL[-1] and 32 μg mL[-1], C. tropicalis are 256 μg mL[-1], 64 μg mL[-1,] and 32 μg mL[-1] and C. krusei are 128 µg mL[-1], 128 µg mL[-1] and 64 µg mL[-1], respectively. Both the variants outperformed epi-1. Specifically for tested Candida spp., var-1 showed two- to four-fold enhancements and var-2 showed two- to eight-fold enhancements compared to epi-1. Electron microscopy confirmed that the mechanism of action involves pore formation thus inducing reactive oxygen species in Candida spp. cell membrane. Computational analysis showed that the peptides have a high tendency to interact with Candida spp. cell membrane proteins such as Exo-β-(1,3)-Glucanase, Secreted Aspartic Proteinase (Sap) 1, and N-terminal Domain Adhesin: Als 9-2, thereby preventing biofilm formation. Conclusions: The in vitro evidence supports the potential use of epi-1 and its variants to be used as an anti-biofilm agent to coat IUDs in the future for therapeutic purposes.}, } @article {pmid39727843, year = {2024}, author = {An, J and Gopalakrishnan, L and Ortega, V and Saul, J and Kadali, R and Bowser, R}, title = {Development of a Sensitive and Reliable Meso Scale Discovery-Based Electrochemiluminescence Immunoassay to Quantify TDP-43 in Human Biofluids.}, journal = {Biosensors}, volume = {14}, number = {12}, pages = {}, pmid = {39727843}, issn = {2079-6374}, support = {Development of TDP-43 Immunoassays//Target ALS/ ; }, mesh = {Humans ; Immunoassay ; *DNA-Binding Proteins/metabolism ; Amyotrophic Lateral Sclerosis/diagnosis ; Luminescent Measurements ; Biomarkers/blood ; Reproducibility of Results ; Electrochemical Techniques ; Biosensing Techniques ; Limit of Detection ; }, abstract = {Transactive response DNA-binding protein of 43 kDa (TDP-43) is a major component of pathological inclusions in various neurodegenerative disorders, including amyotrophic lateral sclerosis and frontotemporal lobar degeneration. The detection of TDP-43 in biofluids is crucial for the development of diagnostic and prognostic indicators of disease and therapeutic development for TDP-43-related proteinopathies. Despite its potential as a biomarker for numerous neurological disorders, the lack of a sensitive and reproducible TDP-43 assay hinders progress in TDP-43-based therapy development, underscoring the need for an effective and standardized method for accurate quantification. Addressing the limitations of sensitivity and reproducibility in existing assays, in this study, we developed and validated a highly sensitive electrochemiluminescence immunoassay on the Meso Scale Discovery platform. The assay demonstrated the detection of full-length TDP-43 in human biofluids with a limit of detection of 4pg/mL, a working range of 4-20,000 pg/mL, and a total assay time of 16 h. In this study, we developed and validated a sensitive immunoassay for the detection of full-length TDP-43 in human biofluids using the Meso Scale Discovery platform. We used this immunoassay to quantify TDP-43 levels in the plasma and serum of healthy controls and ALS patients. Our results indicate a reduction in full-length TDP-43 in the blood of ALS patients compared to healthy controls.}, } @article {pmid39726289, year = {2025}, author = {Kollstrøm, AM and Christiansen, N and Sandvig, A and Sandvig, I}, title = {Dysregulation of synaptic transcripts underlies network abnormalities in ALS patient-derived motor neurons.}, journal = {American journal of physiology. Cell physiology}, volume = {328}, number = {3}, pages = {C1029-C1044}, doi = {10.1152/ajpcell.00725.2024}, pmid = {39726289}, issn = {1522-1563}, support = {//Alf Harborgs fund/ ; //Olav Thon Stiftelsen (Olav Thon Foundation)/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/genetics/pathology/metabolism/physiopathology ; *Motor Neurons/metabolism/pathology ; Humans ; *Synapses/metabolism/genetics/pathology ; C9orf72 Protein/genetics/metabolism ; *Nerve Net/metabolism/pathology/physiopathology ; Mutation ; Action Potentials ; Neuronal Outgrowth ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is characterized by dysfunction and loss of upper and lower motor neurons. Several studies have identified structural and functional alterations in the motor neurons before the manifestation of symptoms, yet the underlying cause of such alterations and how they contribute to the progressive degeneration of affected motor neuron networks remain unclear. Importantly, the short- and long-term spatiotemporal dynamics of neuronal network activity make it challenging to discern how ALS-related network reconfigurations emerge and evolve. To address this, we systematically monitored the structural and functional dynamics of motor neuron networks with a confirmed endogenous C9orf72 mutation. We show that ALS patient-derived motor neurons display time-dependent neural network dysfunction, specifically reduced firing rate and spike amplitude, impaired bursting, but higher overall synchrony in network activity. These changes coincided with altered neurite outgrowth and branching within the networks. Moreover, transcriptional analyses revealed dysregulation of molecular pathways involved in synaptic development and maintenance, neurite outgrowth, and cell adhesion, suggesting impaired synaptic stabilization. This study identifies early synaptic dysfunction as a contributing mechanism resulting in network-wide structural and functional compensation, which may over time render the networks vulnerable to neurodegeneration.NEW & NOTEWORTHY RNA-sequencing of ALS patient-derived motor neurons revealed altered expression of genes involved in cell adhesion, neurite outgrowth, synaptic development and maintenance, and synaptic plasticity. These alterations were accompanied by time-dependent structural impairments and disrupted neuronal activity, suggesting that early synaptic changes and network-wide structural and functional compensations contribute to motor neuron vulnerability in ALS.}, } @article {pmid39725771, year = {2024}, author = {Pagliari, E and Taiana, M and Manzini, P and Sali, L and Quetti, L and Bertolasi, L and Oldoni, S and Melzi, V and Comi, G and Corti, S and Nizzardo, M and Rizzo, F}, title = {Targeting STMN2 for neuroprotection and neuromuscular recovery in Spinal Muscular Atrophy: evidence from in vitro and in vivo SMA models.}, journal = {Cellular and molecular life sciences : CMLS}, volume = {82}, number = {1}, pages = {29}, pmid = {39725771}, issn = {1420-9071}, support = {Craiplo Grant 2020-3623//Fondazione Cariplo/ ; 22739//SMA Europe Grant/ ; }, mesh = {Animals ; *Stathmin/metabolism/genetics ; *Muscular Atrophy, Spinal/therapy/genetics/pathology/metabolism ; Humans ; Mice ; *Disease Models, Animal ; *Motor Neurons/metabolism/pathology ; *Induced Pluripotent Stem Cells/metabolism/cytology ; Neuromuscular Junction/metabolism/pathology ; Neuroprotection ; Dependovirus/genetics ; Genetic Therapy/methods ; }, abstract = {The development of ground-breaking Survival Motor Neuron (SMN) replacement strategies has revolutionized the field of Spinal Muscular Atrophy (SMA) research. However, the limitations of these therapies have now become evident, highlighting the need for the development of complementary targets beyond SMN replacement. To address these challenges, here we explored, in in vitro and in vivo disease models, Stathmin-2 (STMN2), a neuronal microtubule regulator implicated in neurodegenerative diseases like Amyotrophic Lateral Sclerosis (ALS), as a novel SMN-independent target for SMA therapy. Our findings revealed that STMN2 overexpression effectively restored axonal growth and outgrowth defects in induced pluripotent stem cell-(iPSC)-derived motor neurons (MNs) from SMA patients. Intracerebroventricular administration of adeno-associated virus serotype 9 (AAV9) carrying Stmn2 cDNA significantly ameliorated survival rates, motor functions, muscular and neuromuscular junction pathological features in SMA mice, mirrored by in vitro outcomes. Overall, this pioneering study not only provides insight into the therapeutic potential of STMN2 in SMA, but also suggests its broader applications for MN diseases, marking a substantial step forward in addressing the multifaceted challenges of neurological diseases treatment.}, } @article {pmid39724103, year = {2024}, author = {Garcia-Toscano, L and Currey, HN and Hincks, JC and Stair, JG and Lehrbach, NJ and Liachko, NF}, title = {Decreased Hsp90 activity protects against TDP-43 neurotoxicity in a C. elegans model of amyotrophic lateral sclerosis.}, journal = {PLoS genetics}, volume = {20}, number = {12}, pages = {e1011518}, pmid = {39724103}, issn = {1553-7404}, support = {P40 OD010440/OD/NIH HHS/United States ; R01 AG066729/AG/NIA NIH HHS/United States ; I01 BX005762/BX/BLRD VA/United States ; I01 BX004044/BX/BLRD VA/United States ; R35 GM142728/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; *Caenorhabditis elegans/genetics/metabolism ; *Amyotrophic Lateral Sclerosis/genetics/metabolism ; *HSP90 Heat-Shock Proteins/metabolism/genetics ; *Disease Models, Animal ; *DNA-Binding Proteins/metabolism/genetics ; *Caenorhabditis elegans Proteins/metabolism/genetics ; Humans ; Phosphorylation ; Mutation ; Heat-Shock Response/genetics ; TDP-43 Proteinopathies/genetics/metabolism ; }, abstract = {Neuronal inclusions of hyperphosphorylated TDP-43 are hallmarks of disease for most patients with amyotrophic lateral sclerosis (ALS). Mutations in TARDBP, the gene coding for TDP-43, can cause some cases of familial inherited ALS (fALS), indicating dysfunction of TDP-43 drives disease. Aggregated, phosphorylated TDP-43 may contribute to disease phenotypes; alternatively, TDP-43 aggregation may be a protective cellular response sequestering toxic protein away from the rest of the cell. The heat shock responsive chaperone Hsp90 has been shown to interact with TDP-43 and stabilize its normal conformation; however, it is not known whether this interaction contributes to neurotoxicity in vivo. Using a C. elegans model of fALS mutant TDP-43 proteinopathy, we find that loss of function of HSP-90 protects against TDP-43 neurotoxicity and subsequent neurodegeneration in adult animals. This protection is accompanied by a decrease in both total and phosphorylated TDP-43 protein. We also find that hsp-90 mutation or inhibition upregulates key stress responsive heat shock pathway gene expression, including hsp-70 and hsp-16.1, and we demonstrate that normal levels of hsp-16.1 are required for hsp-90 mutation effects on TDP-43. We also observe that the neuroprotective effect due to HSP-90 dysfunction does not involve direct regulation of proteasome activity in C. elegans. Our data demonstrate for the first time that Hsp90 chaperone activity contributes to adverse outcomes in TDP-43 proteinopathies in vivo using a whole animal model of ALS.}, } @article {pmid39722698, year = {2024}, author = {Jiao, L and Yang, J and Wang, W and Liu, X and Fu, Y and Fan, D}, title = {sTREM2 cerebrospinal fluid levels are a potential biomarker in amyotrophic lateral sclerosis and associate with UMN burden.}, journal = {Frontiers in neurology}, volume = {15}, number = {}, pages = {1515252}, pmid = {39722698}, issn = {1664-2295}, abstract = {OBJECTIVES: The aims of this study were to investigate whether CSF sTREM2 may be a potential marker of disease monitoring for amyotrophic lateral sclerosis (ALS).

METHODS: We investigated whether CSF sTREM2 levels are altered in ALS patients and are correlated with upper motor neuron (UMN) burden and disease progression.

RESULTS: CSF sTREM2 was greater in the ALS patients than in the controls (p = 0.002). Elevated CSF sTREM2 was associated with the UMN score (r = 0.38, p = 0.009), ΔFS (r = 0.30, p = 0.04) and serum NFL (lg) (r = 0.35, p = 0.015). As the motor band sign (MBS) score increased, the CSF sTREM2 level increased (p-trend = 0.014). Furthermore, the correlations became stronger (UMN score (r = 0.50, p = 0.01) ΔFRS (r = 0.52, p = 0.008) and serum NFL (lg) (r = 0.55, p = 0.004) when estimated only among patients with a disease duration >12 months.

CONCLUSION: We found that CSF sTREM2 is elevated in ALS patients and may be a novel marker, probably reflecting upper motor unit severity and prognosis.}, } @article {pmid39722495, year = {2025}, author = {García-Ramírez, Y and Cayuela-Fuentes, JM and Mira-Escolano, MP and Maceda-Roldán, LA and Mikulasova, E and Oliva-López, C and Sánchez-Escámez, A and Ciller-Montoya, P and Palomar-Rodríguez, JA}, title = {Characterization, epidemiology, and factors associated with evolution and survival in patients with amyotrophic lateral sclerosis in southeastern Spain, 2008-2021: a population-based study.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {26}, number = {3-4}, pages = {268-280}, doi = {10.1080/21678421.2024.2439454}, pmid = {39722495}, issn = {2167-9223}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/epidemiology/mortality/diagnosis ; Spain/epidemiology ; Male ; Female ; Aged ; Middle Aged ; Aged, 80 and over ; Prevalence ; Incidence ; Adult ; Disease Progression ; }, abstract = {OBJECTIVE: To describe the epidemiology, characteristics, and factors associated with the evolution and survival in patients with amyotrophic lateral sclerosis (ALS) in a region of southeastern Spain.

METHODS: An observational study was carried out in people with a diagnosis of ALS in the period 2008-2021 who were registered in the Information System of Rare Diseases of the Region of Murcia (SIER). We calculated crude and standardized incidence rate (SIR) using European Standard Population of 2013 and point prevalence. The Kaplan-Meier method and the log-rank test were used to estimate and compare survival curves.

RESULTS: We identified 374 cases. The mean age at diagnosis was 66.5 ± 11.7 and 50.3% persons were spinal onset. Mean time from the onset of symptoms to diagnosis was 0.9 ± 1.0 years. The global SIR was 1.95/100,000 person-years (95%CI: 1.77-2.12), which was higher in men (ratio 1.34), and the point prevalence in 2021 was 4.57 per 100,000 (95% CI: 4.46-4.68). There were 297 deaths with a mean age of 69.8 ± 10.8. The median survival from clinical onset was 2 years (95%CI: 1.0-3.0). Factors associated with lower survival were bulbar onset (p < 0.001), older age at the onset of symptoms (p < 0.001), and the absence of riluzole treatment (p = 0.003).

CONCLUSIONS: This study is one of few to evaluate the epidemiological, characteristics, and prognostic factors of ALS in Spain, with findings similar to previous population studies. The use of population-based registries offers reliable information on the magnitude, or evolution in these patients.}, } @article {pmid39722149, year = {2025}, author = {Simão, S and Naumann, LL and de Carvalho, M and Santos, MO and Martins, IP}, title = {Adaptation and Validation of Version B of the Edinburgh Cognitive and Behavioural ALS Screen for the Portuguese Population.}, journal = {Archives of clinical neuropsychology : the official journal of the National Academy of Neuropsychologists}, volume = {40}, number = {3}, pages = {553-564}, doi = {10.1093/arclin/acae118}, pmid = {39722149}, issn = {1873-5843}, support = {GA101017598//European Union's Horizon 2020/ ; }, mesh = {Humans ; Female ; Male ; *Amyotrophic Lateral Sclerosis/complications/diagnosis/psychology ; Middle Aged ; Psychometrics ; Reproducibility of Results ; Portugal ; Aged ; *Neuropsychological Tests/standards ; Adult ; *Cognitive Dysfunction/diagnosis/etiology ; *Cognition Disorders/diagnosis/etiology ; }, abstract = {OBJECTIVE: This study aims to adapt and provide psychometric support for the validation of version B of the Edinburgh Cognitive and Behavioural ALS Screen (ECAS) for the Portuguese population, addressing the need for consistent cognitive evaluations in amyotrophic lateral sclerosis (ALS). A second culturally adapted ECAS screen facilitates the accurate characterization of ALS progression, mitigates learning effects, and supports tailored care management.

METHODS: The adaptation process included forward-backward translation, cultural adaptation, and cognitive debriefing on a prospective sample of 193 ALS patients and 106 controls. A multiple regression analysis identified predictors relevant for establishing ECAS cut-off scores. Psychometric evaluations, including reliability assessments and tests of convergent, construct, and criterion validity, were conducted. Additionally, version A's psychometric properties were reevaluated with complementary analyses and a larger sample.

RESULTS: Version B demonstrated good internal consistency with Cronbach's alpha of 0.802, comparable to the previously established version A. Moderate inter-item correlations further supported reliability, reflecting internal coherence. Equivalence testing between the Portuguese versions supported convergent validity, confirming version B's alignment with version A's theoretical framework. Exploratory factor analysis provided preliminary support for construct validity, and receiver operating characteristic analyses established cut-off values for both versions, revealing moderate sensitivity with a tendency toward false negatives, and higher specificity.

CONCLUSIONS: This study provided evidence for the cultural suitability, reliability, and validity of the Portuguese ECAS B. As evidence supports the equivalence of the Portuguese ECAS versions, they can be used for flexible screenings and applied with the calculated cut-off values to enhance diagnostic accuracy.}, } @article {pmid39722074, year = {2024}, author = {Thompson, EG and Spead, O and Akerman, SC and Curcio, C and Zaepfel, BL and Kent, ER and Philips, T and Vijayakumar, BG and Zacco, A and Zhou, W and Nagappan, G and Rothstein, JD}, title = {A robust evaluation of TDP-43, poly GP, cellular pathology and behavior in an AAV-C9ORF72 (G4C2)66 mouse model.}, journal = {Acta neuropathologica communications}, volume = {12}, number = {1}, pages = {203}, pmid = {39722074}, issn = {2051-5960}, support = {R35 NS132179/NS/NINDS NIH HHS/United States ; R01 5R35NS132179/NS/NINDS NIH HHS/United States ; F32 NS120940/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; *Amyotrophic Lateral Sclerosis/genetics/pathology/metabolism ; *C9orf72 Protein/genetics ; *Disease Models, Animal ; *DNA-Binding Proteins/genetics/metabolism ; *DNA Repeat Expansion/genetics ; Mice ; *Mice, Transgenic ; *Frontotemporal Dementia/genetics/pathology/metabolism ; Dependovirus/genetics ; Humans ; Male ; Behavior, Animal/physiology ; Mice, Inbred C57BL ; }, abstract = {The G4C2 hexanucleotide repeat expansion in C9ORF72 is the major genetic cause of both amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) (C9-ALS/FTD). Despite considerable efforts, the development of mouse models of C9-ALS/FTD useful for therapeutic development has proven challenging due to the intricate interplay of genetic and molecular factors underlying this neurodegenerative disorder, in addition to species differences. This study presents a robust investigation of the cellular pathophysiology and behavioral outcomes in a previously described AAV mouse model of C9-ALS expressing 66 G4C2 hexanucleotide repeats. The model displays key molecular ALS pathological markers including RNA foci, dipeptide repeat (DPR) protein aggregation, p62 positive stress granule formation as well as mild gliosis. However, the AAV-(G4C2)66 mouse model in this study has marginal neurodegeneration with negligible neuronal loss, or clinical deficits. Human C9orf72 is typically associated with altered TAR DNA-binding protein (TDP-43) function, yet studies of this rodent model revealed no significant evidence of TDP-43 dysfunction. While our findings indicate and support that this is a highly valuable robust and pharmacologically tractable model for investigating the molecular mechanisms and cellular consequences of (G4C2) repeat driven DPR pathology, it is not suitable for investigating the development of disease- associated TDP-43 dysfunction or clinical impairment. Our findings underscore the complexity of ALS pathogenesis involving genetic mutations and protein dysregulation and highlight the need for more comprehensive model systems that reliably replicate the multifaceted cellular and behavioral aspects of C9-ALS.}, } @article {pmid39721808, year = {2024}, author = {Almukhlifi, Y and Crowfoot, G and Hutton, A}, title = {Barriers and Facilitators Toward Disaster Knowledge, Skills, and Preparedness among Emergency Medical Services in Saudi Arabia.}, journal = {Prehospital and disaster medicine}, volume = {39}, number = {6}, pages = {395-401}, doi = {10.1017/S1049023X24000670}, pmid = {39721808}, issn = {1945-1938}, mesh = {Humans ; Saudi Arabia ; Male ; Female ; Adult ; *Emergency Medical Services ; Interviews as Topic ; Qualitative Research ; *Disaster Planning ; *Health Knowledge, Attitudes, Practice ; Middle Aged ; }, abstract = {INTRODUCTION: Disasters pose significant challenges globally, affecting millions of people annually. In Saudi Arabia, floods constitute a prevalent natural disaster, underscoring the necessity for effective disaster preparedness among Emergency Medical Services (EMS) workers. Despite their critical role in disaster response, research on disaster preparedness among EMS workers in Saudi Arabia is limited.

STUDY OBJECTIVE/METHODS: The study aimed to explore the disaster preparedness among EMS workers in Saudi Arabia. This study applied an explanatory sequential mixed-methods design to explore disaster preparedness among EMS workers in Saudi Arabia, focusing on the qualitative phase. Semi-structured interviews were conducted with 15 EMS workers from National Guard Health Affairs (NGHA) and Ministry of Health (MOH) facilities in Riyadh, Dammam, and Jeddah. Thematic analysis was conducted following Braun and Clarke's six-step process, ensuring data rigor through Schwandt, et al's criteria for trustworthiness.

FINDINGS: The demographic characteristics of participants revealed a predominantly young, male workforce with varying levels of experience and educational backgrounds. Thematic analysis identified three key themes: (1) Newly/developed profession, highlighting the challenges faced by young EMS workers in acquiring disaster preparedness; (2) Access to opportunities and workplace resources (government versus military), indicating discrepancies in disaster preparedness support between government and military hospitals; and (3) Workplace policies and procedures, highlighting the need for clearer disaster policies, training opportunities, and role clarity among EMS workers.

CONCLUSION: The study underscores the importance of addressing the unique challenges faced by EMS workers in Saudi Arabia to enhance disaster preparedness. Recommendations include targeted support for young EMS professionals, standardization of disaster training across health care facilities, and improved communication of disaster policies and procedures. These findings have implications for policy and practice in disaster management and EMS training in Saudi Arabia.}, } @article {pmid39720511, year = {2024}, author = {Terao, SI and Nosaki, Y and Murao, A and Torii, R and Ogawa, N and Miura, N and Sasaki, Y and Sobue, G}, title = {Onset of age, site and respiratory symptoms are strongly associated with respiratory decline in sporadic amyotrophic lateral sclerosis: a long-term longitudinal study.}, journal = {BMJ neurology open}, volume = {6}, number = {2}, pages = {e000829}, pmid = {39720511}, issn = {2632-6140}, abstract = {OBJECTIVE: The objective of this study is to identify factors influencing progression of respiratory decline from the onset of neurological symptoms to respiratory failure in patients with amyotrophic lateral sclerosis (ALS).

METHODS: In 100 patients with sporadic ALS, %vital capacity (%VC) was continuously measured from the first visit to the respiratory endpoint (REP). Cox proportional hazards model identified factors influencing the duration from onset of ALS to REP (Onset-REP). We performed Kaplan-Meier survival curve analysis for onset-REP according to identified factors.

RESULTS: Onset sites were the upper limb (U-ALS), lower limb (L-ALS), bulbar paralysis (B-ALS) and respiratory paralysis (R-ALS) in 37, 19, 32 and 12 patients, respectively. Duration from the onset of ALS to the onset of respiratory symptoms (Onset-Rp) and REP (Onset-REP) was 16.1 (SD 12.1) and 24.9 months (SD 14.6), respectively. Multivariate analysis revealed that age at onset, site of onset, Onset-Rp and %VC decline rate significantly influenced Onset-REP duration. Elderly patients had a significantly shorter Onset-REP duration. Onset-REP duration did not significantly differ between patients with U-ALS and L-ALS, but was longer in these patients than in those with B-ALS and R-ALS. Onset-REP duration was positively associated with Onset-Rp duration. The average monthly %VC decline rate was -5.6% (SD 3.3). Age at onset, onset site and Onset-Rp duration significantly influenced the %VC decline rate.

CONCLUSIONS: Our findings revealed strong and independent patient-specific factors that influence the Onset-REP duration and the %VC decline rate in patients with ALS. These could inform future clinical trials and interventions considering the respiratory function and natural history of patients with ALS.}, } @article {pmid39720419, year = {2024}, author = {Haikal, C and Weissert, R}, title = {Editorial: Aging, peripheral inflammation, and neurodegeneration.}, journal = {Frontiers in aging neuroscience}, volume = {16}, number = {}, pages = {1529026}, pmid = {39720419}, issn = {1663-4365}, } @article {pmid39719859, year = {2025}, author = {Koumasopoulos, E and Stanitsa, E and Angelopoulou, E and Koros, C and Barbarousi, V and Velonakis, G and Michaletou, C and Alevetsovitis, SK and Constantinides, VC and Kyrozis, A and Stefanis, L and Kroupis, C and Papageorgiou, SG}, title = {Heterozygous p62/SQSTM1 mutation and right temporal variant of frontotemporal dementia: Α case report.}, journal = {Neurocase}, volume = {31}, number = {2}, pages = {70-73}, doi = {10.1080/13554794.2024.2446315}, pmid = {39719859}, issn = {1465-3656}, mesh = {Female ; Humans ; *Frontotemporal Dementia/genetics/pathology ; Heterozygote ; Mutation ; *Sequestosome-1 Protein/genetics ; Aged ; }, abstract = {Mutations in sequestosome 1 (SQSTM1) gene have been associated with frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS), frontotemporal dementia - ALS (FTD-ALS), and very recently, progressive supranuclear palsy (PSP), paget disease of bone (PDB), distal myopathy with rimmed vacuoles (DMRV), and neurodegenerative disorders in childhood. We present a case of right temporal variant of FTD (rtvFTD) with heterozygous mutation (c.823_824del(p.Ser275Phefs *17)) in SQSTM1 gene.}, } @article {pmid39719601, year = {2024}, author = {Kelani, KM and Hegazy, MA and Hassan, AM and Nadim, AH}, title = {Ecological multivariate assisted spectrophotometric methods for determination of antipyrine and benzocaine HCl in presence of antipyrine official impurity and benzocaine HCl degradant: toward greenness and whiteness.}, journal = {BMC chemistry}, volume = {18}, number = {1}, pages = {250}, pmid = {39719601}, issn = {2661-801X}, abstract = {A simple and green chemometrics-assisted spectrophotometric technique has beendeveloped and validated for the determination of antipyrine (ANT) and benzocaine HCl (BEN) along with the official impurity of ANT, antipyrine impurity A (ANT imp-A), and the degradation product of BEN, p-amino benzoic acid (PABA), in their quaternary mixture. Three models were developed and compared: partial least squares (PLS), artificial neural networks (ANN), and multivariate curve resolution-alternating least squares (MCR-ALS) where the four studied drugs were successfully quantified. The quantitative determination of the studied drugs was assessed using percentage recoveries, standard errors of prediction, and root mean square errors of prediction. The ANN model demonstrated the lowest error and the best correlation making it the most accurate method for analysis. The models were constructed in the ranges of 5.0-9.0 µg mL[-1] for ANT, 1.0-5.0 µg mL[-1] for BEN, 0.5-2.5 µg mL[-1] for ANT imp-A, and 0.25-1.25 µg mL[-1] for PABA. The established models successfully determined ANT, BEN, ANT imp-A, and PABA with detection limits of 0.312, 0.178, 0.093, and 0.042 µg mL[-1] for PLS, 0.185, 0.085, 0.001, and 0.034 µg mL[-1] for ANN; and 0.473, 0.240, 0.073, and 0.069 µg mL[-1] for MCR-ALS, respectively. The greenness and the whiteness of the proposed method were assessed using two green evaluating approaches: analytical Eco-scale, and AGREE, along with one white analytical chemistry evaluating tool, RGB. The three proposed models were successfully applied for determination of ANT and BEN in their pharmaceutically co-formulated dosage forms. They are also recommended for stability assays and purity testing of these drugs in quality control laboratories.}, } @article {pmid39719207, year = {2025}, author = {Jirström, E and Matveeva, A and Baindoor, S and Donovan, P and Ma, Q and Morrissey, EP and Arijs, I and Boeckx, B and Lambrechts, D and Garcia-Munoz, A and Dillon, ET and Wynne, K and Ying, Z and Matallanas, D and Hogg, MC and Prehn, JHM}, title = {Effects of ALS-associated 5'tiRNA[Gly-GCC] on the transcriptomic and proteomic profile of primary neurons in vitro.}, journal = {Experimental neurology}, volume = {385}, number = {}, pages = {115128}, doi = {10.1016/j.expneurol.2024.115128}, pmid = {39719207}, issn = {1090-2430}, mesh = {Animals ; *Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology ; Mice ; *Neurons/metabolism ; Cells, Cultured ; *Transcriptome/genetics ; Proteomics ; Mice, Transgenic ; Mice, Inbred C57BL ; Ribonuclease, Pancreatic/genetics ; Humans ; Disease Models, Animal ; *Proteome/metabolism ; }, abstract = {tRNA-derived stress-induced RNAs (tiRNAs) are a new class of small non-coding RNA that have emerged as important regulators of cellular stress responses. tiRNAs are derived from specific tRNA cleavage by the stress-induced ribonuclease angiogenin (ANG). Loss-of-function mutations in the ANG gene are linked to amyotrophic lateral sclerosis (ALS), and elevated levels of specific tiRNAs were recently identified in ALS patient serum samples. However, the biological role of tiRNA production in neuronal stress responses and neurodegeneration remains largely unknown. Here, we investigated the genome-wide regulation of neuronal stress responses by a specific tiRNA, 5'tiRNA[Gly-GCC], which we found to be upregulated in primary neurons exposed to ALS-relevant stresses and in the spinal cord of three ALS mouse models. Whole-transcript RNA sequencing and label-free mass spectrometry on primary neurons transfected with a synthetic mimic of 5'tiRNA[Gly-GCC] revealed predominantly downregulated RNA and protein levels, with more pronounced changes in the proteome. Over half of the downregulated mRNAs contained predicted 5'tiRNA[Gly-GCC] binding sites, indicating that this tiRNA may silence target genes via complementary binding. On the proteome level, we observed reduction in proteins involved in translation initiation and ribosome assembly, pointing to inhibitory effects on translation. Together, these findings suggest that 5'tiRNA[Gly-GCC] is an ALS-associated tiRNA that functions to fine-tune gene expression and supress protein synthesis as part of an ANG-induced neuronal stress response.}, } @article {pmid39718981, year = {2025}, author = {Chen, JQA and McNamara, NB and Engelenburg, HJ and Jongejan, A and Wever, DD and Hopman, K and van Rixel, E and Nijhuis, PJH and de Winter, F and Moerland, PD and Smolders, J and Verhaagen, J and Hamann, J and Huitinga, I}, title = {Distinct transcriptional changes distinguish efficient and poor remyelination in multiple sclerosis.}, journal = {Brain : a journal of neurology}, volume = {148}, number = {6}, pages = {2201-2217}, pmid = {39718981}, issn = {1460-2156}, support = {project 0-TI-01//Start2Cure Foundation/ ; }, mesh = {Humans ; *Remyelination/genetics/physiology ; *Multiple Sclerosis/genetics/pathology/metabolism ; Male ; Female ; Middle Aged ; Adult ; Microglia/pathology/metabolism ; Macrophages/metabolism/pathology ; Aged ; Cohort Studies ; Brain/pathology/metabolism ; }, abstract = {Multiple sclerosis (MS) is a highly heterogeneous disease, with varying remyelination potential across individuals and between lesions. However, the molecular mechanisms underlying the potential to remyelinate remain poorly understood. In this study, we aimed to take advantage of the intrinsic heterogeneity in remyelinating capacity between MS donors and lesions to uncover known and novel pro-remyelinating molecules for MS therapies. To elucidate distinct molecular signatures underlying the potential to remyelinate, we stratified MS donors from the Netherlands Brain Bank cohort (n = 239), based on proportions of remyelinated lesions (RLs), into efficiently remyelinating donors (ERDs; n = 21) and poorly remyelinating donors (PRDs; n = 19). We performed bulk RNA sequencing of RLs, active lesions with ramified and amoeboid microglia/macrophage morphology (ALs non-foamy), active lesions with foamy microglia/macrophage morphology (ALs foamy) and normal-appearing white matter (NAWM) from ERDs and PRDs. We found that ALs non-foamy were positively correlated with remyelination, whereas ALs foamy were not, indicating a role for microglia/macrophage state in influencing remyelination potential. Bioinformatics analyses were performed to identify key pathways and molecules implicated in the remyelination process. We found distinct differences between the donors with differing remyelination potential in comparable MS lesion types. The RLs and ALs non-foamy of ERDs versus PRDs showed upregulation of the epithelial-mesenchymal transition pathway, whereas in ALs foamy of PRDs, inflammation and damage-associated pathways (i.e. MTORC1 signalling, TNF signalling and oxidative phosphorylation) were upregulated in comparison to ALs foamy of ERDs, suggesting that these latter pathways might counteract remyelination. We found genes significantly upregulated in RLs and/or ALs non-foamy of ERDs that have previously been associated with remyelination, including CXCL12, EGF, HGF, IGF2, IL10, PDGFB, PPARG and TREM2, illustrating the strength of our donor and lesion stratification. TGFB1, TGFB2, EGF and IGF1 were determined to be key upstream regulators of genes upregulated in RLs and ALs non-foamy of ERDs. We also identified potential novel pro-remyelinating molecules, such as BTC, GDF10, GDF15, CCN1, CCN4, FGF5, FGF10 and INHBB. Our study identified both known and novel genes associated with efficient remyelination that might facilitate the development of therapeutic strategies to promote tissue repair and clinical recovery in MS.}, } @article {pmid39718871, year = {2025}, author = {Jiang, W and Hua, L and Chakraborty, S}, title = {Degenerate phase-matching for multi-wavelength nonlinear mixing in aperiodic lattice lasers.}, journal = {Optics letters}, volume = {50}, number = {1}, pages = {133-136}, doi = {10.1364/OL.544664}, pmid = {39718871}, issn = {1539-4794}, abstract = {Holographically designed aperiodic lattices (ALs) have proven to be an exciting engineering technique for achieving electrically switchable single- or multi-frequency emissions in terahertz (THz) semiconductor lasers. Here, we employ the nonlinear transfer matrix modeling method to investigate multi-wavelength nonlinear (sum- or difference-) frequency generation within an integrated THz (idler) laser cavity that also supports optical (pump and signal) waves. The laser cavity includes an aperiodic lattice, which engineers the idler photon lifetimes and effective refractive indices. The key findings are the following: (i) the nonlinear conversion efficiency reveals resonant enhancement at those idler frequencies where the photon lifetime is high; (ii) the resonant phase-matching (PM) process between the pump and idler waves has a one-to-one link with the engineered effective index dispersion; and (iii) in the absence of any other dispersion, the lowest threshold, multi-wavelength defect modes of the aperiodic lattice laser have degenerate phase-matched pump frequencies. This set of results will potentially have a significant impact on the wavelength multiplexing in electronically switchable THz-over-fiber communication systems [U.S. patent application 20,150,248,047A1 (3 September 2015)].}, } @article {pmid39718201, year = {2025}, author = {}, title = {Correction to "Access for ALL in ALS: A Large-Scale, Inclusive, Collaborative Consortium to Unlock the Molecular and Genetic Mechanisms of Amyotrophic Lateral Sclerosis" J. D. Berry , S. Paganoni , M. B. Harms , et al., "Access for ALL in ALS: A Large-Scale, Inclusive, Collaborative Consortium to Unlock the Molecular and Genetic Mechanisms of Amyotrophic Lateral Sclerosis," Muscle & Nerve 70, no. 6 (2024): 1140-1150, https://doi.org/10.1002/mus.28244.}, journal = {Muscle & nerve}, volume = {71}, number = {2}, pages = {280}, doi = {10.1002/mus.28317}, pmid = {39718201}, issn = {1097-4598}, } @article {pmid39717968, year = {2024}, author = {Vergini, DE and Hadjipavlou-Litina, D}, title = {"A patent review on arachidonic acid lipoxygenase (LOX) inhibitors for the treatment of neurodegenerative diseases (2018-present)".}, journal = {Expert opinion on therapeutic patents}, volume = {}, number = {}, pages = {1-14}, doi = {10.1080/13543776.2024.2447067}, pmid = {39717968}, issn = {1744-7674}, abstract = {INTRODUCTION: Neuroinflammation is correlated to neurodegenerative diseases like Alzheimer's disease (AD), Amyotrophic Lateral Sclerosis (ALS), Multiple Sclerosis (MS), Huntington Disease (HD), and Parkinson's disease (PD). A lot of recent research and patents are focused on the design and synthesis of arachidonic acid lipoxygenase (ALOX) inhibitors for the treatment of neurodegenerative diseases.

AREAS COVERED: The survey covers natural products, synthesis, hybrids, and assessments of biological effects in biological studies as ALOX inhibitors. A survey of patent publications from 2018 to present, taken from Google Scholar, Espanet, Web of Science, Drugbank, Scopus, or PubMed is analyzed.

EXPERT OPINION: The authors suggest that (i) numerous areas of biology-pharmacology need to be considered: selectivity, in vivo studies, toxicity, bioavailability, and drug-likeness, the mechanism of action in different animals and humans, evaluation of more efficient and selective biological tests; (ii) synthetic method outbalance in the discovery and production of ALOX inhibitors with greater selectivity. Several ALOX inhibitors show promising results for the treatment of neurological disorders. Their clinical evaluation will be critical to assess therapeutic utility. The compounds for which the mechanism of action and their bioavailability are well defined can be used as lead compounds for the treatment of neurodegenerative diseases.}, } @article {pmid39717315, year = {2024}, author = {Alhayali, M}, title = {Concomitant Amyotrophic Lateral Sclerosis and Rheumatoid Arthritis: A Case Report.}, journal = {Cureus}, volume = {16}, number = {11}, pages = {e74301}, pmid = {39717315}, issn = {2168-8184}, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative motor neuron disease that leads to a gradual loss of motor neurons manifesting as progressive weakness, dysarthria, and respiratory decline, with a relatively short life expectancy. Rheumatoid arthritis (RA) is an autoimmune disorder characterized by polyarthritis and affects multiple systems. Motor neuron involvement is rare in rheumatoid arthritis. Here, we report a unique case of a patient with an established diagnosis of ALS who later developed seropositive RA. A 58-year-old male from Baghdad presented to our center with polyarticular joint pain, stiffness, and swelling for about four months, the patient had a history of progressive neurological deficits. The final diagnosis was seropositive rheumatoid arthritis with concomitant amyotrophic lateral sclerosis. While the patient's joint symptoms responded well to methotrexate and prednisolone, he continued to experience a neurological decline. This is one of the few reported cases of concurrent ALS and RA, highlighting the complexity of managing overlapping neurodegenerative and autoimmune conditions.}, } @article {pmid39715603, year = {2024}, author = {Dibling, M and Ortholand, J and Salachas, F and Hesters, A and Tezenas du Montcel, S}, title = {Care Pathway Heterogeneity in Amyotrophic Lateral Sclerosis: Effects of Gender, Age, and Onset.}, journal = {Neuroepidemiology}, volume = {}, number = {}, pages = {1-14}, doi = {10.1159/000542300}, pmid = {39715603}, issn = {1423-0208}, abstract = {BACKGROUND AND OBJECTIVES: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive motor neuron degeneration resulting in loss of muscle function. Care management is restricted to symptomatic and palliative strategies, while clinical manifestations are heterogeneous. However, assessing the timing and benefits of ALS major clinical interventions remains challenging, with varying and nonspecific time-to-events estimates reported in the literature. Consequently, we proposed a retrospective cohort study leveraging healthcare system data to investigate ALS patients care pathway stratified by gender, age class, and onset site to describe strategies diversity and temporality.

METHODS: We developed an algorithm to identify incident ALS patients in the French hospitalization registry and assessed its quality through comparison with literature. We described 7 states, encompassing patient status regarding clinical intervention history, considered 15 transitions, and stratified the analysis depending on 12 different patient profiles, defined according to gender, the presence of symptoms indicative of disease onset site, and age class, to model profile-specific care pathway trajectories. Alongside analysis of median time before transition, we compared acceleration factors resulting from accelerated failure time and time-inhomogeneous models.

RESULTS: We identified 21,153 incident patients with ALS between 2013 and 2022 with a mean age of 67.7±13.1 years at time of in-registry detection, male/female and spinal/bulbar ratios of 1.2 and 1.9, respectively. Noninvasive ventilation (NIV), gastrostomy, tracheostomy, or death at hospital were recorded for 55.24% of the study population. We identified significant variations in utilization based on gender, age class, and onset site. Notably, older age and bulbar onset site accelerated gastrostomy use and spinal onset site was associated with delayed NIV initiation while tracheostomy, mainly considered for younger patients (<64 years), is rarely indicated in ALS care management. Alongside investigation of time-to-event speed, we report extensively the patient profile-specific estimated median delay before clinical event start.

CONCLUSION: Leveraging real-world data from hospital registries provides a large sample size to investigate low prevalence diseases. In conjunction with multistate models, such data enable a comprehensive analysis of care pathways, which revealed variations in ALS management strategies based on patient profiles. By identifying these disparities, our study contributes to enhancing the foreseeability of support strategies for ALS patients.}, } @article {pmid39715100, year = {2025}, author = {Wu, Y and Tian, X and Ma, J and Lin, Y and Ye, J and Wang, Y and Lu, J and Yin, W}, title = {Label-free discrimination analysis of breast cancer tumor and adjacent tissues of patients after neoadjuvant treatment using Raman spectroscopy: a diagnostic study.}, journal = {International journal of surgery (London, England)}, volume = {111}, number = {2}, pages = {1788-1800}, doi = {10.1097/JS9.0000000000002201}, pmid = {39715100}, issn = {1743-9159}, mesh = {Humans ; *Spectrum Analysis, Raman/methods ; *Breast Neoplasms/therapy/pathology/diagnosis/surgery ; Female ; *Neoadjuvant Therapy ; Middle Aged ; Adult ; Mastectomy, Segmental ; Aged ; }, abstract = {BACKGROUND AND OBJECTIVE: Breast-conserving surgery (BCS) plays a crucial role in breast cancer treatment, with a primary focus on ensuring cancer-free surgical margins, particularly for patients undergoing neoadjuvant treatment. After neoadjuvant treatment, tumor regression can complicate the differentiation between breast cancer tumor and adjacent tissues. Raman spectroscopy, as a rapid and non-invasive optical technique, offers the advantage of providing detailed biochemical information and molecular signatures of internal molecular components in tissue samples. Despite its potential, there is currently no research on using label-free Raman spectroscopy to distinguish between breast cancer tumors and adjacent tissues after neoadjuvant treatment. This study intends to distinguish between tumor and adjacent tissues after neoadjuvant treatment in breast cancer through label-free Raman spectroscopy.

METHODS: In this study, the intraoperative frozen samples of breast cancer tumor and adjacent tissue were collected from patients who underwent neoadjuvant treatment during surgery. The samples were examined using Raman confocal microscopy, and Raman spectra were collected by LabSpec6 software. Spectra were preprocessed by Savitz-Golay filter, adaptive iterative reweighted penalized least squares and MinMax normalization method. The differences in Raman spectra between breast cancer tumor and adjacent tissues after neoadjuvant treatment were analyzed by Wilcoxon rank-sum test, with a Bonferroni correction for multiple comparisons. Based on the support vector machine (SVM) method in machine learning, a predictive model for classification was established in the total group and subgroups of different hormone receptor (HR) status, human epidermal growth factor receptor 2 (HER2) status and Ki-67 expression level. The independent test set was used to evaluate the performance of the model, and the area under curve (AUC) of the receiver operating characteristic (ROC) curve, sensitivity, specificity and accuracy of different models were obtained.

RESULT: This study comprised 4260 Raman spectra of breast cancer tumor and adjacent frozen tissue samples from 142 breast cancer patients treated with neoadjuvant treatment. The Raman peaks associated with nucleotides and their metabolites in the Raman spectra of breast cancer tumor tissues were higher in intensities than those of adjacent tissues after neoadjuvant therapy (676 cm -1 : Bonferroni adjusted P < 0.0001; 724 cm -1 : P < 0.0001; 754 cm -1 : P < 0.0001), and the Raman peaks from amide III bands were more intense (1271 cm -1 : P < 0.01). Multivariate curve resolution-alternating least squares (MCR-ALS) decomposition of Raman spectra revealed reduced lipid content and increased collagen and nucleic acid content in breast cancer tumor tissues compared to adjacent tissues following neoadjuvant therapy. The predictive model based on the Raman spectral signature of breast cancer tumor and adjacent tissues after neoadjuvant treatment achieved an AUC of 0.98, with accuracy, sensitivity, and specificity values of 0.89, 0.97, and 0.83, respectively. The AUC of subgroup analysis according to different status of molecular pathological biomarkers was stably around 99%.

CONCLUSION: This study demonstrated that label-free Raman spectroscopy can differentiate tumor and adjacent tissues of breast cancer patients treated with neoadjuvant therapy thorough getting the panoramic perspective of the biochemical compounds for the first time. Our study provided a novel technique for determining the margin status in BCS in breast cancer following neoadjuvant treatment rapidly and precisely.}, } @article {pmid39715090, year = {2025}, author = {Huggon, L and Clayton, EL}, title = {Beginning from the end: the presynaptic terminal as a pathomechanism hub in frontotemporal dementia and amyotrophic lateral sclerosis.}, journal = {Neural regeneration research}, volume = {20}, number = {11}, pages = {3217-3218}, pmid = {39715090}, issn = {1673-5374}, } @article {pmid39714593, year = {2025}, author = {Eldeeb, MA and Hohman, G and Shahid, M}, title = {Novel Approaches in Targeting Cell Surface and Secreted Proteins for Lysosomal Degradation.}, journal = {Chembiochem : a European journal of chemical biology}, volume = {26}, number = {7}, pages = {e202400887}, doi = {10.1002/cbic.202400887}, pmid = {39714593}, issn = {1439-7633}, mesh = {*Lysosomes/metabolism ; Humans ; Proteolysis ; *Membrane Proteins/metabolism ; Animals ; Proteasome Endopeptidase Complex/metabolism ; Autophagy ; *Proteins/metabolism ; }, abstract = {Protein degradation is pivotal for all biochemical aspects of cellular function. In mammalian cells, protein degradation is mediated mainly by the ubiquitin proteasome system (UPS) and the autophagic-lysosomal system (ALS). Over the last two decades, different types of targeted protein degradation approaches have been developed including proteolysis targeting chimeras (PROTACs) and lysosome targeting chimeras (LYTACs), which employ the UPS to degrade intracellular proteins and the ALS to degrade extracellular and membrane proteins respectively. Nevertheless, Current targeted membrane protein degradation approaches face some inherent challenges including limited target protein degradation efficacy and cell type specific applicability. Herein, we highlight some recent developments of novel targeted membrane protein degradation modalities that exhibit wide-applicability and high protein degradation efficiency. These novel membrane protein degraders hold tremendous promise as new pharmacological and biochemical tools in targeting membrane and secretory proteins for lysosomal degradation.}, } @article {pmid39713159, year = {2024}, author = {Wang, YB and Jin, CZ}, title = {Roles of traditional Chinese medicine extracts in hyperuricemia and gout treatment: Mechanisms and clinical applications.}, journal = {World journal of gastroenterology}, volume = {30}, number = {47}, pages = {5076-5080}, pmid = {39713159}, issn = {2219-2840}, mesh = {*Hyperuricemia/drug therapy/blood ; Humans ; *Gout/drug therapy ; *Gastrointestinal Microbiome/drug effects ; *Drugs, Chinese Herbal/therapeutic use/pharmacology ; *Medicine, Chinese Traditional/methods ; *Uric Acid/blood/metabolism ; Gout Suppressants/therapeutic use ; Animals ; }, abstract = {In this manuscript, we comment on the article by Liu et al published in the recent issue of the journal. Hyperuricemia (HUA) has become the second most common metabolic disease after type 2 diabetes mellitus and is the most important risk factor for gout. This discussion focuses on the targets and clinical application value of traditional Chinese medicine (TCM) extracts in the treatment of HUA and gout, emphasizing the role of gut microbiota. Liu et al's study demonstrated that Poecilobdella manillensis protein extract alleviated HUA through multiple mechanisms, including inhibition of uric acid (UA) reabsorption, promotion of UA excretion, repair of intestinal barrier function, and regulation of gut microbiota and metabolome. Unlike the commonly used urate-lowering drugs such as allopurinol and febuxostat, which have clear and single targets, many TCMs have multi-target effects. However, the active components and mechanisms of TCMs are not fully understood, limiting their clinical application in the treatment of HUA and gout. Additionally, the role of gut microbiota in UA metabolic homeostasis needs to be further explored.}, } @article {pmid39712644, year = {2024}, author = {Yusuf, IO and Camille, W and Thompson, PR and Xu, Z}, title = {Protein Citrullination in Amyotrophic Lateral Sclerosis and Other Neurodegenerative Diseases.}, journal = {Journal of experimental neurology}, volume = {5}, number = {4}, pages = {183-191}, pmid = {39712644}, issn = {2692-2819}, support = {R01 NS118145/NS/NINDS NIH HHS/United States ; R35 GM118112/GM/NIGMS NIH HHS/United States ; }, abstract = {Protein citrullination (PC) is a posttranslational modification (PTM) that converts a peptidyl arginine into a peptidyl citrulline. Aberrant PC is a hallmark of neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), Alzheimer's disease, Parkinson's disease, prion disease, and multiple sclerosis. Common among these diseases is a dramatic increase of PC in reactive astrocytes. Some citrullinated proteins have been identified. The most prominent are astrocytic cytoskeletal proteins such as GFAP and vimentin, and myelin protein MBP. Recent investigation in ALS has revealed new changes, including a decreased PC in neurons and an association of PC with myelin protein aggregates. These findings suggest that PC contributes to protein aggregation, neuronal dysfunction, neuroinflammation, and axonal degeneration. However, how PC impact neurodegeneration remains to be understood. Further studies are needed to understand a range of questions, from how PC modulates individual protein functions to its impact on diseases. Because of the PC's robust changes in neurodegenerative diseases, there are also prospects that this PTM may be harnessed as biomarkers, and modulation of this PTM may be an avenue for therapy. In this review, we summarize the current understanding of PC in ALS and other neurodegenerative diseases, the investigative methods for PC, and PC's potential as a biomarker and a therapeutic target.}, } @article {pmid39711523, year = {2024}, author = {Thompson, EG and Spead, O and Akerman, SC and Curcio, C and Zaepfel, BL and Kent, ER and Philips, T and Vijayakumar, BG and Zacco, A and Zhou, W and Nagappan, G and Rothstein, JD}, title = {A robust evaluation of TDP-43, poly GP, cellular pathology and behavior in a AAV- C9ORF72 (G 4 C 2) 66 mouse model.}, journal = {Research square}, volume = {}, number = {}, pages = {}, pmid = {39711523}, issn = {2693-5015}, support = {F32 NS120940/NS/NINDS NIH HHS/United States ; R35 NS132179/NS/NINDS NIH HHS/United States ; }, abstract = {The G4C2 hexanucleotide repeat expansion in C9ORF72is the major genetic cause of both amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) (C9-ALS/FTD). Despite considerable efforts, the development of mouse models of C9-ALS/FTD useful for therapeutic development has proven challenging due to the intricate interplay of genetic and molecular factors underlying this neurodegenerative disorder, in addition to species differences. This study presents a robust investigation of the cellular pathophysiology and behavioral outcomes in a previously described AAV mouse model of C9-ALS expressing 66 G4C2 hexanucleotide repeats. The model displays key molecular ALS pathological markers including RNA foci, dipeptide repeat (DPR) protein aggregation, p62 positive stress granule formation as well as mild gliosis. However, the AAV-(G4C2)66 mouse model in this study has marginal neurodegeneration with negligible neuronal loss, or clinical deficits. Human C9orf72 is typically associated with altered TAR DNA-binding protein (TDP-43) function, yet studies of this rodent model revealed no significant evidence of TDP-43 dysfunction. While our findings indicate and support that this is a highly valuable robust and pharmacologically tractable model for investigating the molecular mechanisms and cellular consequences of (G4C2) repeat driven DPR pathology, it is not suitable for investigating the development of disease- associated TDP-43 dysfunction or clinical impairment. Our findings underscore the complexity of ALS pathogenesis involving genetic mutations and protein dysregulation and highlight the need for more comprehensive model systems that reliably replicate the multifaceted cellular and behavioral aspects of C9-ALS.}, } @article {pmid39709547, year = {2025}, author = {Bakshi, B and Yerraguntla, S and Armon, C and Barkhaus, P and Bertorini, T and Bowser, R and Breevoort, S and Bromberg, M and Brown, A and Carter, GT and Chang, V and Crayle, J and Fullam, T and Greene, M and Heiman-Patterson, T and Jackson, C and Jhooty, S and Mallon, E and Cadavid, JM and Mcdermott, CJ and Pattee, G and Pierce, K and Ratner, D and Sun, Y and Wang, O and Wicks, P and Wiedau, M and Bedlack, R}, title = {ALSUntangled #77: Psilocybin.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {26}, number = {3-4}, pages = {385-388}, doi = {10.1080/21678421.2024.2441274}, pmid = {39709547}, issn = {2167-9223}, mesh = {*Psilocybin/therapeutic use/pharmacology ; Humans ; *Amyotrophic Lateral Sclerosis/drug therapy ; *Hallucinogens/therapeutic use/pharmacology ; Animals ; }, abstract = {ALSUntangled reviews alternate and off-label treatments prompted by patient interest. Here, we review psilocybin, a chemical derived from mushrooms and belonging in the category of drugs known as psychedelics. Psilocybin has plausible mechanisms for slowing ALS progression because of its ability to cross the blood brain barrier and effect neurogenesis and inflammation. Currently, there are no pre-clinical ALS models, case reports, or trials for psilocybin and ALS in the context of disease modifying therapy. Depending on dosing, there can be a high risk of psychological side effects including hallucinations and physical harm. Based on the above information, we do not currently support the use of psilocybin as a means to slow ALS progression.}, } @article {pmid39709476, year = {2024}, author = {Udine, E and Finch, NA and DeJesus-Hernandez, M and Jackson, JL and Baker, MC and Saravanaperumal, SA and Wieben, E and Ebbert, MTW and Shah, J and Petrucelli, L and Rademakers, R and Oskarsson, B and van Blitterswijk, M}, title = {Targeted long-read sequencing to quantify methylation of the C9orf72 repeat expansion.}, journal = {Molecular neurodegeneration}, volume = {19}, number = {1}, pages = {99}, pmid = {39709476}, issn = {1750-1326}, support = {P30 AG072946/AG/NIA NIH HHS/United States ; ALS Association//ALS Association/ ; R21 NS099631/NS/NINDS NIH HHS/United States ; Muscular Dystrophy Association//Muscular Dystrophy Association/ ; P01 NS084974/NS/NINDS NIH HHS/United States ; Robert Packard Center for ALS Research, Johns Hopkins University//Robert Packard Center for ALS Research, Johns Hopkins University/ ; RF1 NS123052/NS/NINDS NIH HHS/United States ; }, mesh = {Humans ; *C9orf72 Protein/genetics ; *DNA Repeat Expansion/genetics ; *DNA Methylation/genetics ; *Amyotrophic Lateral Sclerosis/genetics ; Male ; Female ; Middle Aged ; Aged ; Frontotemporal Dementia/genetics ; Sequence Analysis, DNA/methods ; }, abstract = {BACKGROUND: The gene C9orf72 harbors a non-coding hexanucleotide repeat expansion known to cause amyotrophic lateral sclerosis and frontotemporal dementia. While previous studies have estimated the length of this repeat expansion in multiple tissues, technological limitations have impeded researchers from exploring additional features, such as methylation levels.

METHODS: We aimed to characterize C9orf72 repeat expansions using a targeted, amplification-free long-read sequencing method. Our primary goal was to determine the presence and subsequent quantification of observed methylation in the C9orf72 repeat expansion. In addition, we measured the repeat length and purity of the expansion. To do this, we sequenced DNA extracted from blood for 27 individuals with an expanded C9orf72 repeat.

RESULTS: For these individuals, we obtained a total of 7,765 on-target reads, including 1,612 fully covering the expanded allele. Our in-depth analysis revealed that the expansion itself is methylated, with great variability in total methylation levels observed, as represented by the proportion of methylated CpGs (13 to 66%). Interestingly, we demonstrated that the expanded allele is more highly methylated than the wild-type allele (P-Value = 2.76E-05) and that increased methylation levels are observed in longer repeat expansions (P-Value = 1.18E-04). Furthermore, methylation levels correlate with age at collection (P-Value = 3.25E-04) as well as age at disease onset (P-Value = 0.020). Additionally, we detected repeat lengths up to 4,088 repeats (~ 25 kb) and found that the expansion contains few interruptions in the blood.

CONCLUSIONS: Taken together, our study demonstrates robust ability to quantify methylation of the expanded C9orf72 repeat, capturing differences between individuals harboring this expansion and revealing clinical associations.}, } @article {pmid39709457, year = {2024}, author = {Keeley, O and Mendoza, E and Menon, D and Coyne, AN}, title = {CHMP2B promotes CHMP7 mediated nuclear pore complex injury in sporadic ALS.}, journal = {Acta neuropathologica communications}, volume = {12}, number = {1}, pages = {199}, pmid = {39709457}, issn = {2051-5960}, support = {R00 NS123242/NS/NINDS NIH HHS/United States ; R01 NS132836/NS/NINDS NIH HHS/United States ; R00NS123242//National Institute of Aging/ ; R01NS132836/NS/NINDS NIH HHS/United States ; }, mesh = {*Amyotrophic Lateral Sclerosis/metabolism/pathology/genetics ; Humans ; *Nuclear Pore/metabolism ; *Induced Pluripotent Stem Cells/metabolism ; *Endosomal Sorting Complexes Required for Transport/metabolism/genetics ; Neurons/metabolism/pathology ; DNA-Binding Proteins/metabolism/genetics ; }, abstract = {Alterations to the composition and function of neuronal nuclear pore complexes (NPCs) have been documented in multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis (ALS). Moreover, recent work has suggested that injury to the NPC can at least in part contribute to TDP-43 loss of function and mislocalization, a pathological hallmark of ALS and related neurodegenerative diseases. Collectively, these studies highlight a role for disruptions in NPC homeostasis and surveillance as a significant pathophysiologic event in neurodegeneration. The ESCRT-III nuclear surveillance pathway plays a critical role in the surveillance and maintenance of NPCs and the surrounding nuclear environment. Importantly, pathologic alterations to this pathway and its protein constituents have been implicated in neurodegenerative diseases such as ALS. However, the mechanism by which this pathway contributes to disease associated alterations in the NPC remains unknown. Here we use an induced pluripotent stem cell (iPSC) derived neuron (iPSN) model of sALS to demonstrate that CHMP7/ESCRT-III nuclear maintenance/surveillance is overactivated in sALS neurons. This overactivation is dependent upon the ESCRT-III protein CHMP2B and sustained CHMP2B dependent "activation" is sufficient to contribute to pathologic CHMP7 nuclear accumulation and POM121 reduction. Importantly, partial knockdown of CHMP2B was sufficient to alleviate NPC injury and downstream TDP-43 dysfunction in sALS neurons thereby highlighting CHMP2B as a potential therapeutic target in disease.}, } @article {pmid39708835, year = {2024}, author = {Davalos, L and Kushlaf, H}, title = {Advances in Disease-Modifying Therapeutics for Chronic Neuromuscular Disorders.}, journal = {Seminars in respiratory and critical care medicine}, volume = {}, number = {}, pages = {}, doi = {10.1055/a-2463-3385}, pmid = {39708835}, issn = {1098-9048}, abstract = {Neuromuscular disorders can cause respiratory impairment by affecting the muscle fibers, neuromuscular junction, or innervation of respiratory muscles, leading to significant morbidity and mortality. Over the past few years, new disease-modifying therapies have been developed and made available for treating different neuromuscular disorders. Some of these therapies have remarkable effectiveness, resulting in the prevention and reduction of respiratory complications. For myasthenia gravis (MG), efgartigimod, ravulizumab, rozanolixizumab, and zilucoplan have been Food and Drug Administration (FDA)-approved for the treatment of acetylcholine receptor (AChR) antibody-positive generalized MG in the past 2 years. Rozanolixiumab is also approved for treating MG caused by muscle-specific tyrosine kinase (MuSK) antibodies. The new MG therapeutics target the complement system or block the neonatal fragment crystallizable (Fc) receptors (FcRn), leading to significant clinical improvement. For spinal muscular atrophy (SMA), nusinersen (intrathecal route) and risdiplam (oral route) modify the splicing of the SMN2 gene, increasing the production of normal survival motor neuron (SMN) protein. Onasemnogene abeparvovec is a gene replacement therapy that encodes a functional SMN protein. All SMA medications, particularly onasemnogene abeparvovec, have led to clinically meaningful improvement. For late-onset Pompe disease (LOPD), avalglucosidase alfa has shown a greater improvement in respiratory function, ambulation, and functional outcomes in comparison to alglucosidase alfa, and cipaglucosidase alfa combined with miglustat has shown improvement in respiratory and motor function in a cohort of enzyme replacement therapy-experienced LOPD patients. Amyotrophic lateral sclerosis (ALS) remains a challenge. The two most recent FDA-approved medications, namely sodium phenylbutyrate and tofersen, may slow down the disease by a few months in a selected population but do not stop the progression of the disease.}, } @article {pmid39707523, year = {2024}, author = {Straczkiewicz, M and Burke, KM and Calcagno, N and Premasiri, A and Vieira, FG and Onnela, JP and Berry, JD}, title = {Free-living monitoring of ALS progression in upper limbs using wearable accelerometers.}, journal = {Journal of neuroengineering and rehabilitation}, volume = {21}, number = {1}, pages = {223}, pmid = {39707523}, issn = {1743-0003}, mesh = {*Upper Extremity/physiopathology ; Disease Progression ; *Amyotrophic Lateral Sclerosis/diagnosis/physiopathology ; *Monitoring, Ambulatory/instrumentation/methods ; Accelerometry/instrumentation/methods ; *Wearable Electronic Devices ; *Motor Activity/physiology ; Sensitivity and Specificity ; Humans ; Male ; Female ; Young Adult ; Adult ; Middle Aged ; Aged ; Self Report ; }, abstract = {BACKGROUND: Wearable technology offers objective and remote quantification of disease progression in neurological diseases such as amyotrophic lateral sclerosis (ALS). Large population studies are needed to determine generalization and reproducibility of findings from pilot studies.

METHODS: A large cohort of patients with ALS (N = 202) wore wearable accelerometers on their dominant and non-dominant wrists for a week every two to four weeks and self-entered the ALS Functional Rating Scale-Revised (ALSFRS-RSE) in similar time intervals. Wearable device data were processed to quantify digital biomarkers on four upper limb movements: flexion, extension, supination, and pronation using previously developed and validated open-source methodology. In this study, we determined the association between digital biomarkers and disease progression, studied the impact of study design in terms of required sensor wear-time and sensor position, and determined the impact of self-reported disease onset location on upper limb movements.

RESULTS: The main investigation considered data from a sensor placed on the non-dominant wrist. Participants with higher ALSFRS-RSE scores performed more frequent and faster upper limb movements compared to participants with more advanced disease status. Digital biomarkers exhibited statistically significant change over time while their rate of change was more profound compared to survey responses. Using data from the dominant wrist and changing data inclusion criteria did not alter our findings. ALS disease onset location significantly impacted use of upper limbs. Results presented here were comparable to an earlier study on twenty patients with ALS.

DISCUSSION: Digital health technologies provide sensitive and objective means to quantify ALS disease progression. Interpretable approaches, such as the one used in this paper, can improve patient evaluation and hasten therapeutic development.}, } @article {pmid39706636, year = {2025}, author = {Benatar, M and Robertson, J and Andersen, PM}, title = {Amyotrophic lateral sclerosis caused by SOD1 variants: from genetic discovery to disease prevention.}, journal = {The Lancet. Neurology}, volume = {24}, number = {1}, pages = {77-86}, doi = {10.1016/S1474-4422(24)00479-4}, pmid = {39706636}, issn = {1474-4465}, mesh = {Animals ; Humans ; *Amyotrophic Lateral Sclerosis/genetics/prevention & control ; Disease Models, Animal ; Genetic Therapy/methods ; *Superoxide Dismutase-1/genetics ; }, abstract = {Pathogenic variants in the superoxide dismutase 1 (SOD1) gene were the first identified genetic cause of amyotrophic lateral sclerosis (ALS), in 1993. This discovery enabled the development of transgenic rodent models for studying the biology of SOD1 ALS. The understanding that SOD1 ALS is driven by a toxic gain-of-function mutation has led to therapeutic strategies that aim to lower concentrations of SOD1 protein, an endeavour that has been complicated by the phenotypic heterogeneity of SOD1 ALS. The successful development of genetically targeted therapies to reduce SOD1 expression, together with a better understanding of pre-symptomatic disease and the discovery of neurofilament light protein as a susceptibility/risk biomarker that predicts phenoconversion, has ushered in a new era of trials that aim to prevent clinically manifest SOD1 ALS. The 30-year journey from gene discovery to gene therapy has not only uncovered the pathophysiology of SOD1 ALS, but has also facilitated the development of biomarkers that should aid therapy development for all forms of ALS.}, } @article {pmid39706627, year = {2025}, author = {Andersen, PM and Benatar, M}, title = {Patrikios syndrome and SOD1 ALS.}, journal = {The Lancet. Neurology}, volume = {24}, number = {1}, pages = {27}, doi = {10.1016/S1474-4422(24)00491-5}, pmid = {39706627}, issn = {1474-4465}, } @article {pmid39706377, year = {2025}, author = {Rush, CL and Lyons, C and Gittle, J and Seward, M and Scalia, J and Ho, D and Babu, S and Garret, MA and Brizzi, K and Berry, JD and Fava, M and Lindenberger, E and Vranceanu, AM and , }, title = {Clinician Perspectives Highlight the Need for Early Dyadic Coping Skills for People Living With Amyotrophic Lateral Sclerosis.}, journal = {Journal of pain and symptom management}, volume = {69}, number = {3}, pages = {236-242.e4}, doi = {10.1016/j.jpainsymman.2024.12.010}, pmid = {39706377}, issn = {1873-6513}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/psychology/therapy ; *Adaptation, Psychological ; Female ; Male ; Focus Groups ; *Caregivers/psychology ; Middle Aged ; *Attitude of Health Personnel ; Adult ; Psychological Distress ; Coping Skills ; }, abstract = {CONTEXT: A diagnosis of ALS can be challenging, and many people find ways to adapt. At the same time, emotional distress can arise early after an ALS diagnosis even when high quality multidisciplinary care is provided. When emotional distress occurs, it can become chronic over time, and can affect both the person living with ALS and their care-partner (together called a dyad).

OBJECTIVES: We set out to understand ALS multidisciplinary clinicians' perception of the challenges experienced by people with ALS and care-partners who experience emotional distress after diagnosis and potential benefits of a coping skills program to help these patients and their care-partners, Resilient Together-ALS (RT-ALS).

METHODS: We conducted semi-structured focus groups and individual interviews with 17 clinicians at the Sean M. Healey & AMG Center for ALS at MGH (N = 2 focus groups and five interviews) to elicit feedback on four domains: 1) Psychosocial Needs of ALS Dyads seen in the clinic; 2) Clinic Flow and Referral System to RT-ALS; 3) Clinic Partnership Approach in Support of RT-ALS; 4) RT-ALS Program Content and Manual Format. We conducted rapid data analyses for a time-efficient hybrid inductive-deductive thematic approach.

RESULTS: Clinicians noted that dyadic distress (distress experienced by both patient and their care-partner individually and as a unit), though not universal, is often present early after diagnosis. The response to the proposed program content (dyadic and individual coping skills) and structure (6 weekly virtual sessions delivered within about 2 months after diagnosis) was positive. Multidisciplinary clinicians emphasized the importance of a skills-based program for dyads experiencing elevated early emotional distress for which referral can be easily integrated within clinic flow so as not to not increase provider and dyad burden.

CONCLUSION: RT-ALS program content and structure is acceptable to clinicians. It is imperative to next seek further input from dyads about whether this type of program would be of interest and if yes, to pilot and refine the program for feasibility testing and then efficacy.}, } @article {pmid39706179, year = {2025}, author = {Setsu, S and Morimoto, S and Nakamura, S and Ozawa, F and Utami, KH and Nishiyama, A and Suzuki, N and Aoki, M and Takeshita, Y and Tomari, Y and Okano, H}, title = {Swift induction of human spinal lower motor neurons and robust ALS cell screening via single-cell imaging.}, journal = {Stem cell reports}, volume = {20}, number = {1}, pages = {102377}, pmid = {39706179}, issn = {2213-6711}, mesh = {Humans ; *Motor Neurons/metabolism/cytology ; *Amyotrophic Lateral Sclerosis/pathology/metabolism ; *Induced Pluripotent Stem Cells/cytology/metabolism ; *Single-Cell Analysis/methods ; Cell Differentiation ; *Spinal Cord/cytology ; Time-Lapse Imaging ; Cells, Cultured ; }, abstract = {This study introduces a novel method for rapidly and efficiently inducing human spinal lower motor neurons (LMNs) from induced pluripotent stem cells (iPSCs) to eventually elucidate the pathomechanisms of amyotrophic lateral sclerosis (ALS) and facilitate drug screening. Previous methods were limited by low induction efficiency, poor LMN purity, or labor-intensive induction and evaluation processes. Our protocol overcomes these challenges, achieving around 80% induction efficiency within just two weeks by combining a small molecule-based approach with transcription factor transduction. Moreover, to exclude non-LMN cells from the analysis, we utilized time-lapse microscopy and machine learning to analyze the morphology and viability of iPSC-derived LMNs on a single-cell basis, establishing an effective pathophysiological evaluation system. This rapid, efficient, and streamlined protocol, along with our single-cell-based evaluation method, enables large-scale analysis and drug screening using iPSC-derived motor neurons.}, } @article {pmid39705668, year = {2024}, author = {Khandia, R and Gurjar, P and Priyanka, and Romashchenko, V and Al-Hussain, SA and Zaki, MEA}, title = {Recent advances in stem cell therapy: efficacy, ethics, safety concerns, and future directions focusing on neurodegenerative disorders - a review.}, journal = {International journal of surgery (London, England)}, volume = {110}, number = {10}, pages = {6367-6381}, pmid = {39705668}, issn = {1743-9159}, mesh = {Humans ; *Neurodegenerative Diseases/therapy ; *Stem Cell Transplantation/methods ; }, abstract = {Neurodegeneration refers to the gradual loss of neurons and extensive changes in glial cells like tau inclusions in astrocytes and oligodendrocytes, α-synuclein inclusions in oligodendrocytes and SOD1 aggregates in astrocytes along with deterioration in the motor, cognition, learning, and behavior. Common neurodegenerative disorders are Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), spinocerebellar ataxia (SCA), and supranuclear palsy. There is a lack of effective treatment for neurodegenerative diseases, and scientists are putting their efforts into developing therapies against them. Stem cell therapy has emerged as a hope for neurodegenerative disorders since it is not only the damaged neurons that might be replaced, but other neuromodulators and neuroprotectors are secreted. Stem cell terminal differentiation before implantation ensures the implantation of correct cells and molecular markers like carbonic anhydrase II, CNPase (2',3'-cyclic nucleotide 3'-phosphohydrolase), myelin basic protein (MBP), and myelin oligodendrocyte glycoprotein (MOG) elucidate the differentiation. Secretion of various growth factors like epidermal growth factor (EGF), keratinocyte growth factor (KGF), vascular endothelial growth factor-α (VEGF-α), transforming growth factor (TGF), and macrophage inflammatory protein (MIP) supports cell survival, cell proliferation, blood vessel formation, axon regeneration, and neuroglial functional connection formation at the site of degeneration. Adverse effects of stem cell therapy, like teratogenicity and differentiation in different cells other than the desired one under the influence of microenvironment, are a few key concerns. Post-transplantation improved synaptic plasticity, apoptosis inhibition, and reduction in tau-phosphorylation and amyloid beta (Aβ) production has been observed in Alzheimer's patients. A large number of experimental, preclinical, and clinical studies have been conducted, and encouraging results have been obtained. The present review exhaustively discusses various kinds of stem cells, their usage in treating neurodegenerative disorders, limitations and challenges, and ethical issues related to stem cell therapy.}, } @article {pmid39705453, year = {2024}, author = {Jeong, J and Song, KJ and Lee, JC and Shin, SD and Kim, YJ}, title = {Optimal wearable camera mount locations for medical supervision during simulated out-of-hospital cardiopulmonary resuscitation.}, journal = {Medicine}, volume = {103}, number = {51}, pages = {e40973}, pmid = {39705453}, issn = {1536-5964}, support = {2020R1F1A1076561//National Research Foundation of Korea/ ; }, mesh = {Humans ; *Cardiopulmonary Resuscitation/instrumentation/methods ; Prospective Studies ; *Video Recording ; *Out-of-Hospital Cardiac Arrest/therapy ; *Wearable Electronic Devices ; Male ; Female ; Emergency Medical Technicians/education ; Emergency Medical Services/methods ; Adult ; Simulation Training/methods ; }, abstract = {The quality of the visual information transmitted from a scene is crucial for effective medical supervision in prehospital settings. This study investigated the influence of wearable camera mount locations on visibility during simulated out-of-hospital cardiopulmonary resuscitation. A prospective, observational, non-randomized simulation study was conducted to replicate a cardiac arrest scenario adhering to an advanced life support (ALS) protocol. Seven advanced emergency medical technicians (AEMTs) participated, and 5 camera mount locations were tested: the sternum, forehead, lateral side of the eyelid, mid-nasal, and glabella. Video recordings were captured from the Airway, Intravenous (IV), and Leading providers. Five experienced medical directors independently evaluated visibility scores (1-5) for each procedure with optimal visibility defined as a score of 4 to 5. Glabella mount demonstrated the highest median visibility score and interquartile range (5 [4-5]) and proportion of optimal visibility (77.5%) for most procedures across provider positions. Mixed models revealed significant estimates for the lateral side of the eyelid, mid-nasal, and glabella mounts compared to the sternum, with glabella having the largest effect size (estimate = 1.62). Generalized linear mixed models showed that the glabella mount had the highest odds ratio (OR = 8.07, 95% confidence interval [CI]: 3.01-21.6) to achieve optimal visibility. Wearable camera mount location significantly affected visibility during simulated resuscitation. Mounting cameras closer to eye level provided the most accurate visual data. Further research using objective measures, such as artificial intelligence, and evaluating the visibility of wearable cameras in real-world situations is warranted to optimize simulation-based training for prehospital care.}, } @article {pmid39705326, year = {2025}, author = {}, title = {Correction to Supporting Information for Le et al., Motor neuron disease, TDP-43 pathology, and memory deficits in mice expressing ALS-FTD-linked UBQLN2 mutations.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {122}, number = {2}, pages = {e2424914121}, doi = {10.1073/pnas.2424914121}, pmid = {39705326}, issn = {1091-6490}, } @article {pmid39705260, year = {2024}, author = {Lima, TBWE and Fonseca, JDMD and Silva, AAMD and Vieira, RGDS and Montemezzo, D and Otto-Yáñez, M and Torres-Castro, R and Júnior, METD and Resqueti, VR and Fregonezi, GAF}, title = {Methods to normalize surface electromyography in respiratory muscles: Is it similar between amyotrophic lateral sclerosis and healthy people?.}, journal = {PloS one}, volume = {19}, number = {12}, pages = {e0315846}, pmid = {39705260}, issn = {1932-6203}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology ; *Electromyography/methods ; Male ; Female ; *Respiratory Muscles/physiopathology ; Middle Aged ; Adult ; Cross-Sectional Studies ; Aged ; Case-Control Studies ; Isometric Contraction/physiology ; }, abstract = {The normalization process is important to determine the best approach for normalizing electromyographic signals from respiratory muscles in healthy subjects and those with ALS. The aim of this study is to compare different methods of normalizing the sEMG signal of respiratory muscles in both healthy subjects and those with Amyotrophic Lateral Sclerosis (ALS). This cross-sectional study was conducted in 67 subjects (50 healthy and 17 with ALS). The electrical activity of the sternocleidomastoid (SCM), scalene (ESC), diaphragm (DIA), parasternal (PS), external intercostal (EI), external oblique (EO), and rectus abdominal (RA) muscles were analyzed during maximal inspiratory pressure maneuvers (MIP), maximal nasal inspiratory pressure (SNIP), maximal expiratory pressure (MEP), and maximal voluntary isometric contraction of SCM and ESC (MVICSCM/ESC) and RA (MVICRA) using surface electromyography (sEMG). In the healthy group, inspiratory and expiratory muscles displayed higher electrical activity during MVICSCM/ESC and MIVCRA maneuvers, respectively (p<0.05). In the ALS group, inspiratory muscle activity was higher during the SNIP maneuver, while expiratory muscles showed higher activity during MVICRA (p<0.05). Based on the findings, it can be concluded that the MVIC resulted in greater inspiratory muscle activity, being the ideal method of normalization for inspiratory and expiratory muscles in healthy subjects. In ALS patients, the SNIP maneuver resulted in greater inspiratory muscle activity, while MVIC resulted in greater muscle activity in expiratory muscles.}, } @article {pmid39703667, year = {2024}, author = {Lewis, RD and Keilholz, AN and Smith, CL and Burd, EA and Nichols, NL}, title = {Spinal TNF-α receptor 1 is differentially required for phrenic long-term facilitation (pLTF) over the course of motor neuron death in adult rats.}, journal = {Frontiers in physiology}, volume = {15}, number = {}, pages = {1488951}, pmid = {39703667}, issn = {1664-042X}, support = {T32 OD011126/OD/NIH HHS/United States ; }, abstract = {INTRODUCTION: Intrapleural injections of cholera toxin B conjugated to saporin (CTB-SAP) result in selective respiratory (e.g., phrenic) motor neuron death and mimics aspects of motor neuron disease [(e.g., amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA)], such as breathing deficits. This rodent model allows us to study the impact motor neuron death has on the output of surviving phrenic motor neurons as well as the compensatory mechanisms that are recruited. Microglial density in the phrenic motor nucleus as well as cervical gene expression of markers associated with inflammation (e.g., tumor necrosis factor α; TNF-α) are increased following CTB-SAP-induced phrenic motor neuron death, and ketoprofen (nonsteroidal anti-inflammatory drug) delivery attenuated phrenic long-term facilitation (pLTF) in 7 day (d) CTB-SAP rats but enhanced pLTF in 28d CTB-SAP rats.

METHODS: Here, we worked to determine the impact of TNF-α in the phrenic motor nucleus by: 1) quantifying TNFR1 (a high affinity transmembrane receptor for TNF-α) expression; 2) investigating astrocytes (glial cells known to release TNF-α) by performing a morphological analysis in the phrenic motor nucleus; and 3) determining whether acute TNFR1 inhibition differentially affects phrenic plasticity over the course of CTB-SAP-induced motor neuron loss by delivering an inhibitor for TNF-α receptor 1 (sTNFR1i) in 7d and 28d male CTB-SAP and control rats.

RESULTS: Results revealed that TNFR1 expression was increased on phrenic motor neurons of 28d CTB-SAP rats (p < 0.05), and that astrocytes were increased and exhibited reactive morphology (consistent with an activated phenotype; p < 0.05) in the phrenic motor nucleus of CTB-SAP rats. Additionally, we found that pLTF was attenuated in 7d CTB-SAP rats but enhanced in 28d CTB-SAP rats (p < 0.05) following intrathecal sTNFR1i delivery.

CONCLUSION: This work suggests that we could harness TNFR1 as a potential therapeutic agent in CTB-SAP rats and patients with respiratory motor neuron disease by increasing compensatory plasticity in surviving neurons to improve phrenic motor neuron function and breathing as well as quality of life. Future studies will focus on microglial and astrocytic cytokine release, the role they play in the differential mechanisms of pLTF utilized by 7d and 28d CTB-SAP rats, and potential therapies that target them.}, } @article {pmid39703459, year = {2024}, author = {Oliveira, D and Nishimura, AL}, title = {Editorial: Mechanisms of neurodegeneration in amyotrophic lateral sclerosis and related disorders.}, journal = {Frontiers in cellular neuroscience}, volume = {18}, number = {}, pages = {1531449}, doi = {10.3389/fncel.2024.1531449}, pmid = {39703459}, issn = {1662-5102}, } @article {pmid39703273, year = {2024}, author = {Solano, J and Eni, G and Viswanath, A and Enany, B}, title = {Successful Rescue of Ventricular Fibrillation Electrical Storm Secondary to Acute Myocardial Infarction in a Patient Presenting to a District General Hospital: A Case Report.}, journal = {Cureus}, volume = {16}, number = {11}, pages = {e73959}, pmid = {39703273}, issn = {2168-8184}, abstract = {Ventricular arrhythmia is a critical and challenging cardiovascular complication of myocardial infarction (MI). An electrical storm (ES), characterised by three or more episodes of sustained ventricular arrhythmia within 24 hours, poses a significant life-threatening risk. Standard management includes advanced life support (ALS) protocols and specialised pharmacological interventions. We present the case of a 43-year-old female who presented to the emergency department (ED) following an out-of-hospital ventricular fibrillation (OOHVF) arrest, with the return of spontaneous circulation (ROSC) achieved after multiple defibrillation shocks. Electrocardiography (ECG) revealed anterior ST-segment elevation MI (STEMI) involving the left anterior descending (LAD) artery. During her ED stay, she experienced recurrent ventricular fibrillation (VF) arrests requiring repeated defibrillation, adrenaline, amiodarone, and thrombolysis with alteplase. She was subsequently intubated and transferred to a primary percutaneous coronary intervention (PPCI) centre with intensive care support. Angiography confirmed a 100% occlusion of the LAD, which was successfully treated with stenting. The patient was admitted to the intensive care unit (ICU) and later discharged with full neurological recovery, on secondary prevention and heart failure therapy, with follow-up planned. This case underscores the complexity of managing electrical storms in MI, particularly in non-PPCI centres. It emphasises the importance of thrombolysis as an early reperfusion strategy in STEMI, especially when PPCI is not immediately available.}, } @article {pmid39703094, year = {2025}, author = {De Decker, M and Zelina, P and Moens, TG and Beckers, J and Contardo, M and Dittlau, KS and Van Schoor, E and Ronisz, A and Eggermont, K and Moisse, M and Chandran, S and Veldink, JH and Thal, DR and Van Den Bosch, L and Pasterkamp, RJ and Van Damme, P}, title = {C21ORF2 mutations point towards primary cilia dysfunction in amyotrophic lateral sclerosis.}, journal = {Brain : a journal of neurology}, volume = {148}, number = {3}, pages = {803-816}, pmid = {39703094}, issn = {1460-2156}, support = {C1-C14-17-107//KU Leuven/ ; //Opening the Future Fund (KU Leuven)/ ; 150031//Agency for Innovation by Science and Technology/ ; //ALS Liga België/ ; //National Lottery of Belgium/ ; //European E-Rare-3 project INTEGRALS/ ; //European E-Rare-3 project MAXOMOD/ ; //Stichting ALS Nederland/ ; //Vlaanderen/ ; 772376/ERC_/European Research Council/International ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/pathology/metabolism ; *Cilia/pathology/genetics/metabolism ; *Motor Neurons/metabolism/pathology ; *Mutation/genetics ; Animals ; Female ; Neuromuscular Junction/pathology ; Male ; *Proteins/genetics/metabolism ; }, abstract = {Progressive loss of motor neurons is the hallmark of the neurodegenerative disease amyotrophic lateral sclerosis (ALS), but the underlying disease mechanisms remain incompletely understood. In this study, we investigate the effects of C21ORF2 mutations, a gene recently linked to ALS, and find that primary cilia are dysfunctional. Human patient-derived mutant C21ORF2 motor neurons have a reduced ciliary frequency and length. We report that C21ORF2 is located at the basal body of the primary cilium, and mutations associated with ALS alter this localization. Furthermore, we show that a reduction of C21ORF2 levels in cell lines and motor neurons is sufficient to cause fewer primary cilia and reduced cilial length. This ciliary dysfunction leads to defective downstream sonic hedgehog signalling and reduces the expression of cellular retinoic acid binding protein 1 (CRABP1), a protein involved in motor neuron maintenance and survival. In a compartmentalized co-culture system of motor neurons and muscle cells, these ciliary defects were associated with a reduced ability of neuromuscular junction formation. Interestingly, these cilia defects are seemingly not restricted to C21ORF2 ALS, as we also observed perturbed primary cilia in cultured motor neurons and post-mortem motor cortex from patients with the most common genetic subtype of ALS caused by repeat expansions in the C9ORF72 gene. Finally, overexpression of C21ORF2 in mutant C21ORF2 motor neurons rescued the ciliary frequency and length, CRAPBP1 expression and neuromuscular junction formation, confirming the importance of primary cilia for motor neuron function. These results point towards primary cilia dysfunction contributing to motor neuron degeneration in ALS and open new avenues for further research and interventions for this as yet untreatable disease.}, } @article {pmid39702138, year = {2024}, author = {Chen, C and Meng, J and Cheng, K and Kang, C and Zhou, L and Guo, H and Zhu, X}, title = {Spatial and morphologic features of lenses with different axial lengths in cataract patients: a swept-source optical coherence tomography-based study.}, journal = {BMC ophthalmology}, volume = {24}, number = {1}, pages = {542}, pmid = {39702138}, issn = {1471-2415}, support = {82122017, 82271069, 81870642, 82371040, 81970780, 81470613 and 81670835//National Natural Science Foundation of China/ ; 23Y11909800 and 21S31904900//Science and Technology Innovation Action Plan of Shanghai Science and Technology Commission/ ; SHDC12020111//Clinical Research Plan of Shanghai Shenkang Hospital Development Center/ ; shslczdzk01901//Shanghai Municipal Key Clinical Specialty Program/ ; }, mesh = {Humans ; *Tomography, Optical Coherence/methods ; Female ; Male ; *Cataract/pathology ; *Axial Length, Eye/pathology/diagnostic imaging ; Aged ; Middle Aged ; *Lens, Crystalline/diagnostic imaging/pathology ; Visual Acuity/physiology ; Myopia/physiopathology ; Retrospective Studies ; Aged, 80 and over ; Cataract Extraction ; }, abstract = {BACKGROUND: To investigate the spatial and morphologic features of lenses with different axial length (ALs) in cataract patients using swept-source optical coherence tomography (SS-OCT).

METHODS: Totally 105 eyes of 105 patients scheduled to have cataract surgery were included. Eyes were divided into the control (AL < 24.5 mm), moderate myopia (MM, 24.5 ≤ AL < 26 mm) and high myopia (HM, AL ≥ 26 mm) groups. Spatial features including lens vault (LV) and iris-to-lens distance (ILD), and morphologic features including radii of curvature of anterior and posterior surface (Ra, Rp), lens diameter (LD) and lens thickness (LT) were measured in eight directions by SS-OCT.

RESULTS: Spatially, the HM group had larger LV and ILD than the control group (both P < .05). LV and ILD were negatively correlated with AL, respectively (LV: r = -.484, P < .0001; ILD: r = -.656, P < .0001). Morphologically, both MM and HM groups had greater Ra and Rp than the control group. Ra was positively correlated with AL (r = .622, P < .0001), while the relationship between Rp and AL was non-linear. Moreover, the MM and HM groups had larger LD than the control group (both P < .001). Anterior LT was thinner in the HM than in the MM group (P = .026), while posterior LT between these two groups was similar. When compared in eight directions, similar trends were seen in Ra, Rp and LD, and the HM group showed a greater difference in Ra between horizontal and vertical directions.

CONCLUSIONS: This SS-OCT-based study showed that longer axial length is associated with a flatter lens, which was mainly attributed to the increase of Ra and LD. Longitudinal studies would be necessary to establish a causal relationship and temporal progression.}, } @article {pmid39701414, year = {2025}, author = {Tantoco, AM and Peterson, R and Corbin, B and Coyne, F and Herbst, B and Hunt, S and Levoy, E and Luttrell, H and Shanske, S and Sanyal, S and Dwyer-Matzky, K and Jenkins, AM}, title = {Pediatric to Adult Care Transition in the Hospital Context (PATCH) Tool: A Novel Tool to Assess Pediatric Institutional Guidelines for Inpatient Care of Adults.}, journal = {Academic pediatrics}, volume = {25}, number = {3}, pages = {102625}, doi = {10.1016/j.acap.2024.102625}, pmid = {39701414}, issn = {1876-2867}, mesh = {Humans ; *Transition to Adult Care/standards ; Adult ; *Hospitals, Pediatric ; *Practice Guidelines as Topic ; Child ; Chronic Disease/therapy ; Reproducibility of Results ; Adolescent ; Inpatients ; }, abstract = {OBJECTIVE: The growing number of adults with childhood onset chronic conditions (COCC) is reflected in the increase of adult-aged admissions to pediatric institutions. Despite national bodies advising pediatric institutions to have a pediatric to adult health care transition (HCT) policy, little guidance is available on if or how to include inpatient care. We sought to create a framework-based Pediatric to Adult Transitional Care in the Hospital Context (PATCH) tool to assess how inpatient care of adults is addressed in pediatric institutional guidelines or policies (hereafter guidelines) as a first step towards informing future PATCH guideline development.

METHODS: We used convenience and snowball sampling to obtain 11 pediatric institutional guidelines. Combining the GotTransition core elements with Coller et al's inpatient transition conceptual model through iterative consensus building, we developed the PATCH tool. Interrater reliability was assessed by using mean percent agreement among raters. A three-phase content validity process utilizing existing guidelines refined the finalized tool.

RESULTS: The PATCH tool included 42 items within nine domains. There was a high degree of agreeability among reviewers, and qualitative analysis revealed no missing items. Twenty-five (59%) of our 42 PATCH tool items were present in at least one of the reviewed guidelines, with age being present in all.

CONCLUSIONS: We developed the PATCH tool as a guide for pediatric institutions regarding the care of adolescent and adult patients. The PATCH tool, embedded in multidisciplinary stakeholder discussion and patient- and system-specific knowledge, may help institutions incorporate HCT into processes for adolescent and adult patients with COCCs.}, } @article {pmid39701395, year = {2025}, author = {Force, E and Alvarez, C and Fuentes, A and Maria, A and Bozzolan, F and Debernard, S}, title = {Diet influence on male sexual maturation through interplay between insulin signaling and juvenile hormone in insects.}, journal = {Insect biochemistry and molecular biology}, volume = {177}, number = {}, pages = {104252}, doi = {10.1016/j.ibmb.2024.104252}, pmid = {39701395}, issn = {1879-0240}, mesh = {Animals ; Male ; *Sexual Maturation ; *Insulin/metabolism ; *Juvenile Hormones/metabolism ; Signal Transduction ; *Moths/growth & development/metabolism/physiology/genetics ; Diet ; Receptor, Insulin/metabolism ; Female ; }, abstract = {In animals, sexual maturation coincides with the development of sexual behaviors and reproductive system. These developmental events are influenced by diet and governed by endocrine signals. Here, for the first time in insects, we explored functional links between nutrition and juvenile hormone (JH) in the male reproductive physiology through the insulin signaling pathway (ISP) acting as a transducer of nutritional signals. We turned to the male moth Agrotis ipsilon for which sexual maturation, including accessory sex glands (ASGs) development concomitantly with antennal lobes (ALs) maturation for female sex pheromone processing and display of sexual behavior, is known to be JH- and diet-dependent. Indeed, a diet rich in sugars with sodium was previously shown to accelerate sexual maturation, which was achieved from the third day of adult life. In this study, we demonstrated that such a diet raised i) the expression of JH signaling actors (Methoprene-tolerant, Taiman, and Krüppel homolog 1) in ALs and ASGs, ii) the biosynthesis and circulating levels of JH, and iii) the expression of both insulin receptor (InR) and insulin-like peptides (ILPs) in corpora allata (CAs) and brain respectively. Insulin injection raised JH biosynthesis following increased HMG-CoA reductase expression in CAs; opposite effects were induced in InR-deficient males. Thus, we highlighted that promoting effects of a diet composed of sugars with sodium on male sexual maturation results from an early induction of ISP causing an increase in JH biosynthesis followed by a potentiation of JH actions on the development of ASGs and ALs in A. ipsilon.}, } @article {pmid39700696, year = {2025}, author = {Ghaderi, S and Mohammadi, S and Fatehi, F}, title = {Current evidence of arterial spin labeling in amyotrophic lateral sclerosis: A systematic review.}, journal = {Clinical neurology and neurosurgery}, volume = {249}, number = {}, pages = {108691}, doi = {10.1016/j.clineuro.2024.108691}, pmid = {39700696}, issn = {1872-6968}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnostic imaging/physiopathology ; *Spin Labels ; *Cerebrovascular Circulation/physiology ; *Brain/diagnostic imaging/blood supply ; Magnetic Resonance Imaging/methods ; }, abstract = {OBJECTIVE: This study aimed to evaluate the utility of arterial spin labeling (ASL) in assessing cerebral blood flow (CBF) changes in amyotrophic lateral sclerosis (ALS), and its potential as a biomarker for early diagnosis.

METHODS: A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Studies that employed ASL to compare CBF between ALS patients and healthy controls were included.

RESULTS: Seven studies were included. A consistent finding across these studies was hypoperfusion in both the motor and non-motor regions, particularly in the frontotemporal cortex. Hypoperfusion in motor regions was correlated with functional impairment and was observed prior to structural changes, suggesting its potential as an early biomarker. There is limited evidence to suggest that monitoring changes in CBF patterns in the brain. Besides, limited findings showed initial hyperperfusion in regions not yet involved in the pathological process, and progressing hypoperfusion in regions with increasing pathological burden.

CONCLUSIONS: This review highlights the potential of ASL as a valuable tool for understanding the neurovascular dysfunction in ALS. Further research is required to validate its clinical utility for diagnosing ALS and monitoring disease progression.}, } @article {pmid39698283, year = {2024}, author = {Kos, JA and Langiu, M and Hellyer, SD and Gregory, KJ}, title = {Pharmacology, Signaling and Therapeutic Potential of Metabotropic Glutamate Receptor 5 Negative Allosteric Modulators.}, journal = {ACS pharmacology & translational science}, volume = {7}, number = {12}, pages = {3671-3690}, pmid = {39698283}, issn = {2575-9108}, abstract = {Metabotropic glutamate receptors are a family of eight class C G protein-coupled receptors regulating higher order brain functions including cognition and motion. Metabotropic glutamate receptors have thus been heavily investigated as potential drug targets for treating neurological disorders. Drug discovery efforts directed toward metabotropic glutamate receptor subtype 5 (mGlu5) have been particularly fruitful, with a wealth of drug candidates and pharmacological tools identified. mGlu5 negative allosteric modulators (NAMs) are promising novel therapeutics for developmental, neuropsychiatric and neurodegenerative disorders (e.g., Alzheimer's Disease, Huntington's Disease, Parkinson's Disease, amyotrophic lateral sclerosis, autism spectrum disorders, substance use disorders, stroke, anxiety and depression) and show promise in ameliorating adverse effects induced by other medications (e.g., L-dopa induced dyskinesia in Parkinson's Disease). However, despite preclinical success, mGlu5 NAMs are yet to reach the market due to poor safety and efficacy profiles in clinical trials. Herein, we review the physiology and signal transduction of mGlu5. We provide a comprehensive critique of therapeutic options with respect to mGlu5 inhibitors, spanning from orthosteric antagonists to NAMs. Finally, we address the challenges associated with drug development and highlight future directions to guide rational drug discovery of safe and effective novel therapeutics.}, } @article {pmid39697625, year = {2024}, author = {Zhao, X and Huang, S}, title = {Plasma extracellular vesicle: a novel biomarker for neurodegenerative disease diagnosis.}, journal = {Extracellular vesicles and circulating nucleic acids}, volume = {5}, number = {3}, pages = {569-573}, pmid = {39697625}, issn = {2767-6641}, abstract = {Extracellular vesicles (EVs) are membrane-bound structures that carry proteins, lipids, RNA, and DNA, playing key roles in cell communication and material transport. Recent research highlights their potential as disease biomarkers due to their stability in bodily fluids. This study explores using tau and TDP-43 proteins in plasma EVs as diagnostic biomarkers for frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). Analyzing plasma EVs from clinical cohorts, the study found that the 3R/4R tau ratio and TDP-43 levels effectively differentiate between diagnostic groups with high accuracy. Notably, plasma EV biomarkers demonstrate higher diagnostic accuracy and stability compared to direct plasma testing, providing new insights and approaches for future research and clinical practice. Further research is needed to validate these biomarkers in diverse populations and to establish standardized protocols. Future studies should continue to explore the potential of EV biomarkers in a broader range of neurodegenerative diseases and delve deeper into the mechanisms of EV secretion and sorting to enhance their diagnostic utility.}, } @article {pmid39697444, year = {2024}, author = {He, SY and Cai, WC and Su, WM and Duan, QQ and Jiang, Z and Yin, KF and Gu, XJ and Chen, YP and Cao, B}, title = {Quantifying the split-elbow sign: a comprehensive study in amyotrophic lateral sclerosis.}, journal = {Frontiers in neurology}, volume = {15}, number = {}, pages = {1499668}, pmid = {39697444}, issn = {1664-2295}, abstract = {PURPOSE: The split-elbow sign (SES), characterized by preferential dysfunction of the biceps brachii compared to the triceps, is a clinical feature observed in amyotrophic lateral sclerosis (ALS). However, the quantified SES index has not been extensively investigated, and its role in diagnosing ALS remains unknown. Therefore, this study aimed to investigate the split-elbow index (SEI) derived from compound muscle action potential (CMAP), motor unit number index (MUNIX), and echo intensity (EI) in ALS.

METHODS: A cohort comprising 70 individuals diagnosed with ALS, along with 41 disease controls and 40 healthy controls, was recruited for the study. The SEI was calculated by dividing the recorded values of CMAP, MUNIX, and EI obtained over the biceps brachii by the corresponding value measured in the triceps, resulting in SEICMAP, SEIMUNIX, and SEIEI, respectively. Receiver operating characteristic (ROC) curves of the three methods were used for comparison. Statistical analyses were performed using SPSS V.26.0 and R software.

RESULTS: Both SEICMAP and SEIMUNIX exhibited significant reductions in ALS patients compared to that in controls (PSEICMAp  < 0.0001, PSEIMUNIX < 0.0001), while SEIEI showed an elevation (P < 0.0001). Furthermore, there was a notable decrease in SEIMUNIX values as the disease progressed (p < 0.001). Moreover, ROC for SEIMUNIX exhibited superior diagnostic performance (AUC = 0.846), and a comprehensive diagnostic approach combining SEICMAP, SEIMUNIX, and SEIEI resulted in AUC (0.90) on the ROC curve.

CONCLUSION: Our study suggested that SES has emerged as a significant clinical characteristic in ALS and indicated the potential of SES indicators as biomarkers for both diagnosis and assessment of disease progression in ALS.}, } @article {pmid39696694, year = {2024}, author = {El-Khatib, SM and Vagadia, AR and Le, ACD and Baulch, JE and Ng, DQ and Du, M and Johnston, KG and Tan, Z and Xu, X and Chan, A and Acharya, MM}, title = {BDNF augmentation reverses cranial radiation therapy-induced cognitive decline and neurodegenerative consequences.}, journal = {Acta neuropathologica communications}, volume = {12}, number = {1}, pages = {190}, pmid = {39696694}, issn = {2051-5960}, support = {R01 CA251110/CA/NCI NIH HHS/United States ; R01 CA276212/CA/NCI NIH HHS/United States ; R01 CA262213/CA/NCI NIH HHS/United States ; P30CA062203//National Institutes of Health (UC Irvine Comprehensive Cancer Center)/ ; P30 CA062203/CA/NCI NIH HHS/United States ; UL1TR001414//National Institutes of Health (UC Irvine and National Center for Advancing Translational Sciences, NCATS)/ ; UL1 TR001414/TR/NCATS NIH HHS/United States ; R01CA276212/NH/NIH HHS/United States ; }, mesh = {Animals ; *Brain-Derived Neurotrophic Factor/metabolism/genetics ; *Cognitive Dysfunction/etiology/metabolism ; *Cranial Irradiation/adverse effects ; Mice ; Male ; Mice, Inbred C57BL ; Neuroprotective Agents/pharmacology ; Neurodegenerative Diseases/radiotherapy ; Hippocampus/metabolism/radiation effects/drug effects ; Female ; }, abstract = {Cranial radiation therapy (RT) for brain cancers is often associated with the development of radiation-induced cognitive dysfunction (RICD). RICD significantly impacts the quality of life for cancer survivors, highlighting an unmet medical need. Previous human studies revealed a marked reduction in plasma brain-derived neurotrophic factor (BDNF) post-chronic chemotherapy, linking this decline to a substantial cognitive dysfunction among cancer survivors. Moreover, riluzole (RZ)-mediated increased BDNF in vivo in the chemotherapy-exposed mice reversed cognitive decline. RZ is an FDA-approved medication for ALS known to increase BDNF in vivo. In an effort to mitigate the detrimental effects of RT-induced BDNF decline in RICD, we tested the efficacy of RZ in a cranially irradiated (9 Gy) adult mouse model. Notably, RT-exposed mice exhibited significantly reduced hippocampal BDNF, accompanied by increased neuroinflammation, loss of neuronal plasticity-related immediate early gene product, cFos, and synaptic density. Spatial transcriptomic profiling comparing the RT + Vehicle with the RT + RZ group showed gene expression signatures of neuroprotection of hippocampal excitatory neurons post-RZ. RT-exposed mice performed poorly on learning and memory, and memory consolidation tasks. However, irradiated mice receiving RZ (13 mg/kg, drinking water) for 6-7 weeks showed a significant improvement in cognitive function compared to RT-exposed mice receiving vehicle. Dual-immunofluorescence staining, spatial transcriptomics, and biochemical assessment of RZ-treated irradiated brains demonstrated preservation of synaptic integrity and mature neuronal plasticity but not neurogenesis and reduced neuroinflammation concurrent with elevated BDNF levels and transcripts compared to vehicle-treated irradiated brains. In summary, oral administration of RZ represents a viable and translationally feasible neuroprotective approach against RICD.}, } @article {pmid39696212, year = {2024}, author = {Giusti, A and Pukrittayakamee, P and Wannarit, K and Thongchot, L and Janwanishstaporn, S and Nkhoma, K and Venkatapuram, S and Harding, R}, title = {How to deliver person-centred care for people living with heart failure: a multi stakeholder interview study with patients, caregivers and healthcare professionals in Thailand.}, journal = {BMC health services research}, volume = {24}, number = {1}, pages = {1570}, pmid = {39696212}, issn = {1472-6963}, support = {GHRU 16/136/54//National Institute of Health Research (NIHR) Global Health Research Unit on Health System Strengthening in Sub-Saharan Africa, King's College London/ ; GA-00937//Funds for Graduate Women (FfGW)/ ; }, mesh = {Humans ; *Heart Failure/therapy/psychology ; Thailand ; *Caregivers/psychology ; Male ; *Patient-Centered Care ; Cross-Sectional Studies ; Female ; Middle Aged ; *Qualitative Research ; *Health Personnel/psychology ; Aged ; Adult ; Interviews as Topic ; }, abstract = {CONTEXT: Heart failure has high, growing global prevalence, morbidity and mortality, and is a leading cause of death with serious health-related suffering in low- and middle-income countries. Person-centred care (PCC) is a critical component of high-quality healthcare and is particularly vital in the context of a serious illness such as heart failure. However, there are limited data exploring PCC in this population in low- and middle-income settings.

AIM: The aim of this study was to explore how clinical services could respond to the PCC needs of individuals living with heart failure in Thailand, with potential for adaptation in other settings. The specific objectives were (i) to understand the experiences and needs of persons living with heart failure, their caregivers and HCPs; (ii) to explore specific practical actions that can help deliver PCC for heart failure patients in this setting.

METHODS: Cross-sectional qualitative study. In depth, semi-structured interviews were conducted in Thailand with heart failure patients (n = 14), their caregivers (n = 10) and healthcare professionals (n = 12). Framework analysis was conducted with deductive coding to populate an a priori coding frame based on Santana et al's PCC model (2018) and Giusti et al's systematic review (2020), with further inductive coding of novel findings to expand the frame. The study is reported in accordance with the consolidated criteria for reporting qualitative research guidelines (COREQ).

RESULTS: The findings reveal specific practice actions that deliver PCC for persons living with heart failure in Thailand, such as (i) compassionate communication by healthcare professionals; (ii) effective teamwork amongst multidisciplinary healthcare professionals; (iii) proactive responses to physical, psychosocial, relational and information needs of patients and caregivers; (iv) engaging patients and families in symptom management; (v) providing opportunities for patients to be cared for in the community; and (vi) responding to the social determinants of health, illness and healthcare access.

CONCLUSION: Person-centred healthcare systems must aim to address the social determinants of illness and place focus on community- and home-based care. Heart failure patients and caregivers must be supported to self-manage, including how to recognise symptoms and take appropriate action. Delivering PCC in such a way has the potential to improve outcomes for patients, enhance patients' sense of agency and experiences of care, improve health equity, and reduce hospital admissions, relieving pressure on the hospital system and reducing overall costs of care.}, } @article {pmid39694549, year = {2024}, author = {Ma, YL and Qiu, T and Xu, XL and Wang, LX and Zhuang, PY}, title = {[Analysis of clinical characteristics of amyotrophic lateral sclerosis patients initially diagnosed with abnormal laryngeal function].}, journal = {Zhonghua er bi yan hou tou jing wai ke za zhi = Chinese journal of otorhinolaryngology head and neck surgery}, volume = {59}, number = {12}, pages = {1293-1298}, doi = {10.3760/cma.j.cn115330-20240630-00388}, pmid = {39694549}, issn = {1673-0860}, support = {82271155//National Natural Science Foundation of China/ ; 2020J011212//Fujian Provincial Natural Science Foundation/ ; }, mesh = {Humans ; Male ; *Amyotrophic Lateral Sclerosis/diagnosis/physiopathology ; Female ; Middle Aged ; Retrospective Studies ; Aged ; Adult ; Larynx/physiopathology ; }, abstract = {Objective: To study the laryngeal functional characteristics of patients with amyotrophic lateral sclerosis (ALS)disease diagnosed at the voice clinic. Methods: A retrospective analysis(case series study) was conducted on the laryngeal functional characteristics of 7 patients [2 males, 5 females, age ranged from 43 to 76(60.85±13.18)]with motor neuron disease who visited the voice clinic and were ultimately diagnosed by neurologists. The data included laryngostroboscopy, fiberoptic endoscopic examination of swallowing(FEES), acoustic analysis and laryngeal electromyography(LEMG). Descriptive methods were used for analysis. Results: ①There were 2 males and 5 females, with an average age of (60.85±13.18) years. They had previously visited the otolaryngology department more than twice, visit frequency with an average of 3.57 and an average diagnosis time of 12.28 months. The main complaints of the patient at the time of treatment were voice change, dysphagia or vocal fatigue. ②LEMG: Among 7 cases, 4 cases demonstrated neurogenic damage, all of which were bilateral, and 3 cases showed normal findings on examination. Spontaneous potentials (SP) were present in three cases for more than 6 months, with the longest duration being 24 months. Three cases exhibited the coexistence of spontaneous potential and reinnervated motor unit potentials (MUPs), and two cases showed bundle tremor potential.③Laryngostroboscopy revealed bilateral vocal fold asymmetry and glottic insufficiency in 7 cases, and decreased vocal cord movement in 4 cases, and vocal cord atrophy in 5 cases. FEES showed that 7 patients presented with mild to severe swallowing dysfunction, 3 cases had soft palate insufficiency and mild to severe food residues in the epiglottic valley and pyriform fossa. 1 case showed leakage and 1 case showed aspiration. Conclusions: Patients presenting with initial symptoms of abnormal laryngeal function should be vigilant for the possibility of motor neuron disease, especially when laryngostroboscopy reveals abnormal vocal fold movement and swallowing dysfunction. LEMG examination reveals bilateral neurogenic damage, prolonged spontaneous potential, coexistence of spontaneous potential and reinnervated MUPs, and the appearance of bundle tremor potential, which is beneficial for early detection of motor neuron disease.}, } @article {pmid39694468, year = {2025}, author = {Cornell, PY and Gadkari, G and Hua, CL and Smith, L and Johnson, A and Schwartz, L and Rahman, M and Thomas, KS}, title = {Risk of Hospitalization Among Assisted Living Residents Dually Enrolled in Medicare and Medicaid.}, journal = {Journal of the American Medical Directors Association}, volume = {26}, number = {2}, pages = {105421}, doi = {10.1016/j.jamda.2024.105421}, pmid = {39694468}, issn = {1538-9375}, mesh = {Humans ; United States ; *Hospitalization/statistics & numerical data ; *Assisted Living Facilities ; Retrospective Studies ; Male ; Female ; Aged ; *Medicare/statistics & numerical data ; *Medicaid/statistics & numerical data ; Aged, 80 and over ; }, abstract = {OBJECTIVES: To examine how risk of hospitalization among assisted living (AL) residents differs by dual enrollment in Medicare and Medicaid and by the percent of dually enrolled individuals in an AL community.

DESIGN: Retrospective cohort study.

SETTING AND PARTICIPANTS: We used Medicare data from 2008 to 2018 and a national directory of licensed AL communities to identify Medicare beneficiaries with a change in their ZIP+4 code suggesting a new residence in an AL.

METHODS: We estimated linear regression models of hospitalization onto interactions of residents' dual enrollment status and categories of the AL community's percentage of dually enrolled residents. In the models, we adjusted for person-level clinical and demographic characteristics, year-fixed effects, and fixed effects for the AL residents' prior ZIP code.

RESULTS: Among 620,542 Medicare beneficiaries who moved to an AL community, the 1-year risk of hospitalization was higher for dually enrolled residents compared with Medicare-only residents. In adjusted models, dually enrolled residents in high-dual AL communities (>50% dually enrolled) had an 7.4% higher risk of hospital admission compared with dually enrolled residents in low-dual AL communities. Medicare-only beneficiaries in high-dual AL communities had a 9.4% higher risk of hospitalization than Medicare-only beneficiaries in low-dual ALs.

CONCLUSIONS AND IMPLICATIONS: The proportion of residents in an AL community who were dually enrolled was associated with residents' risk of hospitalization, regardless of their dual enrollment status. Additional research is needed to understand whether differences observed in residents' risk of hospitalization are due to differences in the types of services provided, unmeasured resident acuity, or the quality of care delivered in these settings.}, } @article {pmid39693933, year = {2025}, author = {Taisei Ito, and Ohuchi, K and Kurita, H and Murakami, T and Takizawa, S and Fujimaki, A and Murata, J and Oida, Y and Hozumi, I and Kitaichi, K and Inden, M}, title = {Neuroprotective effects of activated fibroblast growth factor receptor 1 via the suppression of p53 accumulation against poly-PR-mediated toxicity.}, journal = {Biochemical and biophysical research communications}, volume = {743}, number = {}, pages = {151181}, doi = {10.1016/j.bbrc.2024.151181}, pmid = {39693933}, issn = {1090-2104}, mesh = {*Tumor Suppressor Protein p53/metabolism/genetics ; *Receptor, Fibroblast Growth Factor, Type 1/metabolism/genetics/antagonists & inhibitors ; Animals ; Mice ; *Neuroprotective Agents/pharmacology ; Cell Line ; Proto-Oncogene Proteins c-mdm2/metabolism/genetics ; Cell Survival/drug effects ; Motor Neurons/metabolism/drug effects ; Humans ; }, abstract = {A GGGGCC hexanucleotide repeat expansion (HRE) within the C9orf72 gene is a major causative factor in amyotrophic lateral sclerosis (ALS). This aberrant HRE results in the generation of five distinct dipeptide repeat proteins (DPRs). Among the DPRs, poly-PR accumulates in the nucleus and exhibits particularly strong toxicity to motor and cortical neurons. Fibroblast growth factor receptor 1 (FGFR1) is known to promote neurogenesis and inhibit apoptosis in neurons. Nevertheless, there has been no previous report of its neuroprotective effects against poly-PR toxicity. The objective of this study was to investigate the neuroprotective effects of FGFR1 activation in poly-PR-expressing NSC34 motor neuron-like cells. RT-qPCR analysis in NSC34 cells showed that Fgfr1 was the most highly expressed member of the Fgfr family in NSC34 cells. The activation of FGFR1 by FGF2, a common ligand for all FGFRs, exerted neuroprotective effects against the toxicity of poly-PR. Additionally, FGFR1 activation was observed to enhance cell viability through the PI3K-AKT pathway, while the contribution of the MEK-ERK pathway was found to be limited. Furthermore, FGFR1 activation suppressed the accumulation of p53 protein and promoted its degradation through increased murine double minute 2 (MDM2), an E3 ubiquitin ligase that targets p53. The neuroprotective effects were attenuated by PD173074, a selective FGFR1 inhibitor or Nutlin-3a, an inhibitor of the p53-MDM2 interaction. Overall, these findings suggest that FGFR1 activation provides neuroprotection against poly-PR toxicity. Consequently, this study suggests the potential utility of FGFR1 activation as a therapeutic strategy for ALS.}, } @article {pmid39693632, year = {2024}, author = {Hausmann, F and Caldi Gomes, L and Hänzelmann, S and Khatri, R and Oller, S and Gebelin, M and Parvaz, M and Tzeplaeff, L and Pasetto, L and Zhou, Q and Zelina, P and Edbauer, D and Pasterkamp, RJ and Rehrauer, H and Schlapbach, R and Carapito, C and Bonetto, V and Bonn, S and Lingor, P}, title = {A dataset profiling the multiomic landscape of the prefrontal cortex in amyotrophic lateral sclerosis.}, journal = {GigaScience}, volume = {13}, number = {}, pages = {}, pmid = {39693632}, issn = {2047-217X}, support = {01GM1917A//Bundesministerium für Bildung und Forschung/ ; CRC1192//DFG/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/genetics/metabolism ; *Prefrontal Cortex/metabolism/pathology ; Humans ; Female ; Mice ; Male ; Animals ; Mice, Transgenic ; Transcriptome ; Proteome ; Disease Models, Animal ; Aged ; Gene Expression Profiling/methods ; Middle Aged ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disease, which still lacks effective disease-modifying therapies. Similar to other neurodegenerative disorders, such as Alzheimer and Parkinson disease, ALS pathology is presumed to propagate over time, originating from the motor cortex and spreading to other cortical regions. Exploring early disease stages is crucial to understand the causative molecular changes underlying the pathology. For this, we sampled human postmortem prefrontal cortex (PFC) tissue from Brodmann area 6, an area that exhibits only moderate pathology at the time of death, and performed a multiomic analysis of 51 patients with sporadic ALS and 50 control subjects. To compare sporadic disease to genetic ALS, we additionally analyzed PFC tissue from 4 transgenic ALS mouse models (C9orf72-, SOD1-, TDP-43-, and FUS-ALS) using the same methods. This multiomic data resource includes transcriptome, small RNAome, and proteome data from female and male samples, aimed at elucidating early and sex-specific ALS mechanisms, biomarkers, and drug targets.}, } @article {pmid39691755, year = {2025}, author = {Sood, A and Mishra, GV and Kar, P and Khandelwal, S and Gaur, S and Manuja, N}, title = {Amyotrophic lateral sclerosis in a tricenarian female.}, journal = {Radiology case reports}, volume = {20}, number = {2}, pages = {1121-1123}, pmid = {39691755}, issn = {1930-0433}, abstract = {Amyotrophic lateral sclerosis (ALS) is a motor neuron disease characterized by the progressive degeneration of the upper and lower motor neurons. This disease is mostly observed in patients of the 6th decade or above, and it is extremely rare to observe this pathology in patients less than 50 years of age. This manuscript depicts the magnetic resonance imaging findings of ALS showing a wine glass sign in a 31-year-old female from a rural area with complaints of progressive limb weakness and muscle wasting.}, } @article {pmid39691422, year = {2024}, author = {Fang, K}, title = {Modulation of the central nervous system immune response and neuroinflammation via Wnt signaling in health and neurodegenerative diseases.}, journal = {Ibrain}, volume = {10}, number = {4}, pages = {462-476}, pmid = {39691422}, issn = {2769-2795}, abstract = {The immune response in the central nervous system (CNS) is a highly specialized and tightly regulated process essential for maintaining neural health and protecting against pathogens and injuries. The primary immune cells within the CNS include microglia, astrocytes, T cells, and B cells. They work together, continuously monitor the CNS environment for signs of infection, injury, or disease, and respond by phagocytosing debris, releasing cytokines, and recruiting other immune cells. In addition to providing neuroprotection, these immune responses must be carefully balanced to prevent excessive inflammation that can lead to neuronal damage and contribute to neurodegenerative diseases. Dysregulated immune responses in the CNS are implicated in various neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. Wnt signaling is a crucial pathway in the CNS that regulates various cellular processes critical for brain development, function, and maintenance. Despite enhancing immune responses in the health CNS, dysregulated Wnt signaling exacerbates neuroinflammation in the neurodegenerative brains. This review summarized the role of Wnt signaling in regulating immune response under different conditions. We then examined the role of immune response in healthy brains and during the development of neurodegenerative diseases. We also discussed therapeutic intervention in various neurodegenerative diseases through the modulation of the Wnt signaling pathway and neuroinflammation and highlighted challenges and limitations in current clinical trials.}, } @article {pmid39690447, year = {2025}, author = {Koch, R and Nagoshi, E}, title = {Examining the potential involvement of NONO in TDP-43 proteinopathy in Drosophila.}, journal = {The European journal of neuroscience}, volume = {61}, number = {1}, pages = {e16632}, pmid = {39690447}, issn = {1460-9568}, support = {310030_189169//Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung/ ; 310030_189169//The Swiss National Science Foundation/ ; }, mesh = {Animals ; *DNA-Binding Proteins/metabolism/genetics ; *TDP-43 Proteinopathies/metabolism/pathology/genetics ; *Drosophila Proteins/metabolism/genetics ; RNA-Binding Proteins/metabolism/genetics ; Drosophila ; Neurons/metabolism ; Longevity ; Cell Nucleus/metabolism ; }, abstract = {The misfolding and aggregation of TAR DNA binding protein-43 (TDP-43), leading to the formation of cytoplasmic inclusions, emerge as a key pathological feature in a spectrum of neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and frontotemporal lobar dementia (FTLD). TDP-43 shuttles between the nucleus and cytoplasm but forms nuclear bodies (NBs) in response to stress. These NBs partially colocalise with nuclear speckles and paraspeckles that sequester RNAs and proteins, thereby regulating many cellular functions. The laboratory of Steven Brown has recently found that the non-POU domain-containing octamer-binding protein (NONO), a component of paraspeckles, forms novel nuclear speckle-like structures in mouse cortical neurons in response to stress and sleep deprivation. These findings suggest the possibility of a functional link between NONO and TDP-43, potentially contributing to TDP-43 proteinopathy. Here, we demonstrate that pathological phenotypes caused by TDP-43 gain of function-locomotor defects and life span shortening-are exacerbated by silencing the Drosophila homolog of NONO, no on or off transient A (NonA). Additionally, NonA silencing results in an increase in nuclear TDP-43 NBs. These results provide supporting evidence for the functional link between NONO and TDP-43 and lay the foundation for dissecting underlying mechanisms.}, } @article {pmid39690343, year = {2025}, author = {Lamichhane, S and Seo, JE and Jeong, JH and Lee, S and Lee, S}, title = {Ideal animal models according to multifaceted mechanisms and peculiarities in neurological disorders: present and challenges.}, journal = {Archives of pharmacal research}, volume = {48}, number = {1}, pages = {62-88}, pmid = {39690343}, issn = {1976-3786}, support = {Research grant 2024//Chung-Ang University/ ; NRF-2016R1A6A1A03011325//Ministry of Education/ ; }, mesh = {Animals ; *Disease Models, Animal ; Humans ; *Nervous System Diseases/physiopathology/pathology/drug therapy ; Translational Research, Biomedical/methods ; }, abstract = {Neurological disorders, encompassing conditions such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS), pose a significant global health challenge, affecting millions worldwide. With an aging population and increased life expectancy, the prevalence of these disorders is escalating rapidly, leading to substantial economic burdens exceeding trillions of dollars annually. Animal models play a crucial role in understanding the underlying mechanisms of these disorders and developing effective treatments. Various species, including rodents, non-human primates, and fruit flies, are utilized to replicate specific aspects of human neurological conditions. However, selecting the ideal animal model requires careful consideration of its proximity to human disease conditions and its ability to mimic disease pathobiology and pharmacological responses. An Animal Model Quality Assessment (AMQA) tool has been developed to facilitate this selection process, focusing on assessing models based on their similarity to human conditions and disease pathobiology. Therefore, integrating intrinsic and extrinsic factors linked to the disease into the study's objectives aids in constructing a biological information matrix for comparing disease progression between the animal model and human disease. Ultimately, selecting an ideal animal disease model depends on its predictive, face, and construct validity, ensuring relevance and reliability in translational research efforts.}, } @article {pmid39689069, year = {2024}, author = {Junedahl, E and Lundgren, P and Andersson, E and Gupta, V and Råmunddal, T and Rawshani, A and Rawshani, A and Riva, G and Arnetorp, I and Hessulf, F and Herlitz, J and Djärv, T}, title = {The evidence supporting AHA guidelines on adult cardiopulmonary resuscitation (CPR).}, journal = {PloS one}, volume = {19}, number = {12}, pages = {e0309241}, pmid = {39689069}, issn = {1932-6203}, mesh = {Humans ; *Cardiopulmonary Resuscitation/standards/methods ; *American Heart Association ; Adult ; *Practice Guidelines as Topic ; United States ; *Heart Arrest/therapy ; Evidence-Based Medicine/standards ; }, abstract = {BACKGROUND: Guidelines for the management of cardiac arrest play a crucial role in guiding clinical decisions and care. We examined the strength and quality of evidence underlying these recommendations in order to elucidate strengths and gaps in knowledge.

METHODS: Using the 2020 American Heart Association (AHA) Guidelines for Adult CPR, we subdivided all recommendations into advanced life support (ALS), basic life support (BLS), and recovery after cardiac arrest, as well as a more granular categorization by topic (i.e. the intervention or evaluation recommended). The Class of Recommendation (COR) and Level of Evidence (LOE) for each were reviewed. Additionally, we reviewed the 2023 guidelines to ensure the inclusion of the most recent updates.

RESULTS: We noted 254 recommendations, of which 181 were ALS, 69 were BLS, and 4 were recovery after resuscitation. In total, only 2 (1%) had the most robust evidence (LOE A), while 23% were at LOE B-NR (Non-Randomized), 15% at LOE B-R (Randomized), 50% at LOE C-LD (Limited Data), and 12% relied on expert opinion LOE C-EO (Expert Opinion). Despite the strength of ALS recommendations (Class 1, 2a, or 2b), none had LOE A. In BLS, no recommendations were supported by LOE A. For BLS, 7% of recommendations had LOE C (C-LD or C-EO). The evidence for specific BLS topics, such as airway management, was notably low. Among ALS topics, neurological prognostication had relatively stronger evidence.

CONCLUSIONS: Only 26 out of the 81 COR 1 recommendations (32%) were supported by LOE A or B, indicating a strong discrepancy between the strength of recommendation and the underlying evidence in cardiac arrest guidelines. The findings underscore a pressing need for more rigorous research, particularly randomized trials.}, } @article {pmid39688956, year = {2024}, author = {Spargo, TP and Gilchrist, L and Hunt, GP and Dobson, RJB and Proitsi, P and Al-Chalabi, A and Pain, O and Iacoangeli, A}, title = {Statistical examination of shared loci in neuropsychiatric diseases using genome-wide association study summary statistics.}, journal = {eLife}, volume = {12}, number = {}, pages = {}, pmid = {39688956}, issn = {2050-084X}, support = {DRIVE-Health Centre for Doctoral Training//King's College London/ ; 772376-EScORIAL//Horizon 2020/ ; ES/L008238/1//Economic and Social Research Council/ ; 633413//Horizon 2020/ ; MR/L501529/1/MRC_/Medical Research Council/United Kingdom ; 259867//European Community's Health Seventh Framework Programme/ ; MR/R024804/1/MRC_/Medical Research Council/United Kingdom ; 10.35802/222811/WT_/Wellcome Trust/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; }, mesh = {Humans ; *Genome-Wide Association Study ; Genetic Predisposition to Disease ; Mental Disorders/genetics ; Amyotrophic Lateral Sclerosis/genetics ; Schizophrenia/genetics ; Genetic Loci ; Parkinson Disease/genetics ; Alzheimer Disease/genetics ; }, abstract = {Continued methodological advances have enabled numerous statistical approaches for the analysis of summary statistics from genome-wide association studies. Genetic correlation analysis within specific regions enables a new strategy for identifying pleiotropy. Genomic regions with significant 'local' genetic correlations can be investigated further using state-of-the-art methodologies for statistical fine-mapping and variant colocalisation. We explored the utility of a genome-wide local genetic correlation analysis approach for identifying genetic overlaps between the candidate neuropsychiatric disorders, Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), frontotemporal dementia, Parkinson's disease, and schizophrenia. The correlation analysis identified several associations between traits, the majority of which were loci in the human leukocyte antigen region. Colocalisation analysis suggested that disease-implicated variants in these loci often differ between traits and, in one locus, indicated a shared causal variant between ALS and AD. Our study identified candidate loci that might play a role in multiple neuropsychiatric diseases and suggested the role of distinct mechanisms across diseases despite shared loci. The fine-mapping and colocalisation analysis protocol designed for this study has been implemented in a flexible analysis pipeline that produces HTML reports and is available at: https://github.com/ThomasPSpargo/COLOC-reporter.}, } @article {pmid39688717, year = {2024}, author = {Ghaderi, S and Fatehi, F and Kalra, S and Mohammadi, S and Batouli, SAH}, title = {Involvement of the left uncinate fasciculus in the amyotrophic lateral sclerosis: an exploratory longitudinal multi-modal neuroimaging and neuropsychological study.}, journal = {Brain structure & function}, volume = {230}, number = {1}, pages = {8}, pmid = {39688717}, issn = {1863-2661}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnostic imaging/pathology/physiopathology ; Female ; Male ; Middle Aged ; *Diffusion Tensor Imaging/methods ; Longitudinal Studies ; *Magnetic Resonance Imaging ; Aged ; Neuropsychological Tests ; Adult ; Neural Pathways/diagnostic imaging/physiopathology/pathology ; White Matter/diagnostic imaging/pathology ; Neuroimaging/methods ; Multimodal Imaging ; }, abstract = {To investigate the microstructural integrity, tract volume analysis, and functional connectivity (FC) alterations of the left uncinate fasciculus (UF) in patients with amyotrophic lateral sclerosis (ALS) compared to healthy controls (HCs). Fourteen limb-onset ALS patients were recruited at baseline and ten at follow-up, along with 14 HCs. All participants underwent 3D T1-weighted, diffusion tensor imaging and kurtosis imaging (DTI/DKI), and resting-state functional MRI (rs-fMRI) using a 3 Tesla scanner with 64-channel coils. Eight metrics of diffusion, rs-FC of the left UF, and graph theory analyses were extracted. Statistical group comparisons and correlation analysis for significant diffusion metrics were also conducted. Significantly lower radial kurtosis (RK), mean kurtosis (MK), and higher DTI diffusivity metrics were observed in the left UF of ALS patients than in HCs. RK and MK were correlated with various cognitive scores, particularly executive function and visuospatial ability. The volume of the left UF was positively correlated only with RK and MK at follow-up. While rs-FC analysis did not reveal group differences, a negative functional link between the left UF and cerebellum was observed in HCs but not in patients. Graph theory analysis suggested decreased connectivity in baseline patients and potential compensatory effects during the follow-up. Our study reveals microstructural abnormalities and potential network changes in left UF. DKI metrics, especially RK and MK, may be more sensitive biomarkers than DTI metrics, particularly longitudinally. Diffusion changes appear to precede volume and functional connectivity alterations, suggesting diffusion as a potential early biomarker.}, } @article {pmid39688317, year = {2025}, author = {Tseriotis, VS and Eleftheriadou, K and Mavridis, T and Konstantis, G and Falkenburger, B and Arnaoutoglou, M}, title = {Is the Swallow Tail Sign a Useful Imaging Biomarker in Clinical Neurology? A Systematic Review.}, journal = {Movement disorders clinical practice}, volume = {12}, number = {2}, pages = {134-147}, pmid = {39688317}, issn = {2330-1619}, support = {//Hellenic Academic Libraries Link/ ; }, mesh = {Humans ; *Magnetic Resonance Imaging/methods ; *Parkinson Disease/diagnostic imaging ; *Substantia Nigra/diagnostic imaging/pathology ; Biomarkers ; *Parkinsonian Disorders/diagnostic imaging ; }, abstract = {BACKGROUND: Loss of dorsolateral nigral hyperintensity (DNH) in iron-sensitive sequences of Magnetic Resonance Imaging (MRI), also described as "swallow tail sign" (STS) loss, has shown promising diagnostic value in Parkinson's Disease (PD) and Atypical Parkinsonian Syndromes (APS).

OBJECTIVE: To conduct a bibliometric analysis on substantia nigra MRI and a systematic review on the clinical utility of STS visual assessment on Susceptibility-Weighted Imaging in various clinical entities.

METHODS: VOSviewer's keyword co-occurrence network was employed using Web of Science (WOS). Complying with the PRISMA statement, we searched MEDLINE, WOS, SCOPUS, ProQuest and Google Scholar for peer-reviewed studies conducted in vivo, excluding quantitative imaging techniques.

RESULTS: DNH is a relatively novel parameter in substantia nigra MRI literature. Our SWI-focused review included 42 studies (3281 patients). Diagnostic accuracy of STS loss for PD/APS differentiation from controls and for Lewy Body Dementia differentiation from other dementias was 47.8-98.5% and 76-90%, respectively, with poorer capacity, however, in delineating PD from APS. STS evaluation in idiopathic REM sleep behavior disorder, a sign of prodromal PD, was typically concordant with nuclear scans, identifying subjects with high conversion risk. Iron deposition can affect STS in Multiple Sclerosis and STS loss in Amyotrophic Lateral Sclerosis is linked with multisystem degeneration, with poorer prognosis. In healthy individuals iron-induced microvessel changes are suspected for false positive results.

CONCLUSION: STS assessment exhibits potential in different settings, with a possibly intermediate role in the diagnostic work-up of various conditions. Its clinical utility should be explored further, through standardized MRI protocols on larger cohorts.}, } @article {pmid39687363, year = {2024}, author = {Stal, C and Covătaru, C and De Wolf, Q and Ignat, T and Pecheniuk, D and Lazăr, C}, title = {Towards a spatial data repository for archaeological research in the Romanian Mostiștea Basin and Danube Valley.}, journal = {Data in brief}, volume = {57}, number = {}, pages = {111119}, doi = {10.1016/j.dib.2024.111119}, pmid = {39687363}, issn = {2352-3409}, abstract = {Spatial data are crucial in archaeological research, where orthophotos, digital elevation models, and 3D models are widely used for mapping, documenting, and monitoring archaeological sites. The introduction of affordable and compact unmanned aerial vehicles (UAVs) has significantly advanced the use of UAV-based photogrammetry in the past 20 years. Recently, compact airborne systems have also enabled the capture of thermal, multispectral, and aerial laser scanning data. This paper presents the data acquired with different platforms and sensors at Chalcolithic archaeological sites in Romania's Mostiștea Basin and Danube Valley. Since laser scanning and photogrammetry generate large data volumes, data storage and dissemination must also be carefully considered. Based on a thorough study of system performance, data acquisition and processing methods, and data outputs, a workflow for the systematic mapping and documentation of sites has been proposed. Given the experience obtained in the last 5 summer campaigns (2018-2023), 19 sites have been accurately mapped, of which 5 sites are mapped using airborne laser scanning. 18 sites are documented using multispectral photogrammetry, and for 17 sites, interactive image-based 3D models are acquired using true-color photogrammetry. All data are stored on a publicly accessible website for visualization, as well as on an open-data platform for data exchange. For the multispectral data, a raster tile service has been implemented, allowing the use of the data in a GIS environment.}, } @article {pmid39687198, year = {2024}, author = {Pappalardo, XG and Jansen, G and Amaradio, M and Costanza, J and Umeton, R and Guarino, F and De Pinto, V and Oliver, SG and Messina, A and Nicosia, G}, title = {Inferring gene regulatory networks of ALS from blood transcriptome profiles.}, journal = {Heliyon}, volume = {10}, number = {23}, pages = {e40696}, pmid = {39687198}, issn = {2405-8440}, abstract = {One of the most robust approaches to the prediction of causal driver genes of complex diseases is to apply reverse engineering methods to infer a gene regulatory network (GRN) from gene expression profiles (GEPs). In this work, we analysed 794 GEPs of 1117 human whole-blood samples from Amyotrophic Lateral Sclerosis (ALS) patients and healthy subjects reported in the GSE112681 dataset. GRNs for ALS and healthy individuals were reconstructed by ARACNe-AP (Algorithm for the Reconstruction of Accurate Cellular Networks - Adaptive Partitioning). In order to examine phenotypic differences in the ALS population surveyed, several datasets were built by arranging GEPs according to sex, spinal or bulbar onset, and survival time. The designed reverse engineering methodology identified a significant number of potential ALS-promoting mechanisms and putative transcriptional biomarkers that were previously unknown. In particular, the characterization of ALS phenotypic networks by pathway enrichment analysis has identified a gender-specific disease signature, namely network activation related to the radiation damage response, reported in the networks of bulbar and female ALS patients. Also, focusing on a smaller interaction network, we selected some hub genes to investigate their inferred pathological and healthy subnetworks. The inferred GRNs revealed the interconnection of the four selected hub genes (TP53, SOD1, ALS2, VDAC3) with p53-mediated pathways, suggesting the potential neurovascular response to ALS neuroinflammation. In addition to being well consistent with literature data, our results provide a novel integrated view of ALS transcriptional regulators, expanding information on the possible mechanisms underlying ALS and also offering important insights for diagnostic purposes and for developing possible therapies for a disease yet incurable.}, } @article {pmid39686920, year = {2025}, author = {Sodagari, S and Sodagari, N}, title = {Examining vaccination-related adverse events in frequent neurodegenerative diseases.}, journal = {Brain, behavior, & immunity - health}, volume = {43}, number = {}, pages = {100902}, pmid = {39686920}, issn = {2666-3546}, abstract = {This study investigates adverse events following vaccination in patients with four neurodegenerative diseases: Amyotrophic Lateral Sclerosis (ALS), Alzheimer's disease, Multiple Sclerosis (MS), and Parkinson's disease. We applied advanced data processing techniques to analyze symptom patterns and severity scores across these disease groups. Patients were identified through filtering, and symptom clusters were extracted to group similar symptoms into distinct clusters, and severity scores were computed based on hospitalization and death reports. A chi-squared test was performed to assess the statistical significance of adverse event distributions among the diseases for different vaccines. The results reveal that ALS patients exhibit severe respiratory symptoms post-vaccination, while Alzheimer's patients report significant respiratory and gastrointestinal issues. MS patients commonly experience general symptoms such as fatigue, while Parkinson's patients face exacerbated motor symptoms. Notably, our analysis showed no significant difference in adverse event reporting rates between COVID-19 and pneumococcal vaccines across these disease groups. This research provides new insights into disease-specific responses to vaccines, emphasizing the importance of personalized monitoring and treatment strategies to mitigate risks and improve clinical outcomes in these vulnerable populations.}, } @article {pmid39684507, year = {2024}, author = {Tournezy, J and Léger, C and Klonjkowski, B and Gonzalez-Dunia, D and Szelechowski, M and Garenne, A and Mathis, S and Chevallier, S and Le Masson, G}, title = {The Neuroprotective Effect of the X Protein of Orthobornavirus Bornaense Type 1 in Amyotrophic Lateral Sclerosis.}, journal = {International journal of molecular sciences}, volume = {25}, number = {23}, pages = {}, pmid = {39684507}, issn = {1422-0067}, support = {Evaluation of the therapeutic potential of the Borna virus X protein and X-derived peptides in ALS//Association pour la recherche sur la Sclérose Latérale Amyotrophique/ ; Award Fabrice Le Mouaher 2020//Fondation pour la Recherche Médicale/ ; trampoline grant 20219//Association Francaise contre les Myopathies/ ; X protein and ALS//Rotary Club of Bergerac/ ; }, mesh = {Animals ; *Amyotrophic Lateral Sclerosis/metabolism/genetics/pathology ; *Motor Neurons/metabolism/pathology ; Mice ; *Neuroprotective Agents/pharmacology ; *Disease Models, Animal ; Adenosine Triphosphate/metabolism ; Viral Proteins/metabolism/genetics ; Mice, Transgenic ; Humans ; }, abstract = {In amyotrophic lateral sclerosis (ALS), early mitochondrial dysfunction may contribute to progressive motor neuron loss. Remarkably, the ectopic expression of the Orthobornavirus bornaense type 1 (BoDV-1) X protein in mitochondria blocks apoptosis and protects neurons from degeneration. Therefore, this study examines the neuroprotective effects of X protein in an ALS mouse model. We first tested in vitro the effect of the X-derived peptide (PX3) on motoneurons primary cultures of SOD1[G93A] mice. The total intracellular adenosine triphosphate (ATP) content was measured after incubation of the peptide. We next tested in vivo the intramuscular injection of X protein using a canine viral vector (CAV2-X) and PX3 intranasal administrations in SOD1[G93A] mice. Disease onset and progression were assessed through rotarod performance, functional motor unit analysis via electrophysiology, and motor neuron survival by immunohistochemistry. The results showed that in vitro PX3 restored the ATP level in SOD1[G93A] motor neurons. In vivo, treated mice demonstrated better motor performance, preserved motor units, and higher motor neuron survival. Although life expectancy was not extended in this severe mouse model of motor neuron degeneration, the present findings clearly demonstrate the neuroprotective potential of X protein in a model of ALS. We are convinced that further studies may improve the therapeutic impact of X protein with optimized administration methods.}, } @article {pmid39684324, year = {2024}, author = {Toader, C and Tataru, CP and Munteanu, O and Serban, M and Covache-Busuioc, RA and Ciurea, AV and Enyedi, M}, title = {Decoding Neurodegeneration: A Review of Molecular Mechanisms and Therapeutic Advances in Alzheimer's, Parkinson's, and ALS.}, journal = {International journal of molecular sciences}, volume = {25}, number = {23}, pages = {}, pmid = {39684324}, issn = {1422-0067}, mesh = {Humans ; *Alzheimer Disease/therapy/metabolism/genetics ; *Parkinson Disease/therapy/genetics/metabolism ; *Amyotrophic Lateral Sclerosis/therapy/genetics/metabolism ; Animals ; Neurodegenerative Diseases/therapy/metabolism/genetics ; Drug Delivery Systems ; Gene Editing ; }, abstract = {Neurodegenerative diseases, such as Alzheimer's, Parkinson's, ALS, and Huntington's, remain formidable challenges in medicine, with their relentless progression and limited therapeutic options. These diseases arise from a web of molecular disturbances-misfolded proteins, chronic neuroinflammation, mitochondrial dysfunction, and genetic mutations-that slowly dismantle neuronal integrity. Yet, recent scientific breakthroughs are opening new paths to intervene in these once-intractable conditions. This review synthesizes the latest insights into the underlying molecular dynamics of neurodegeneration, revealing how intertwined pathways drive the course of these diseases. With an eye on the most promising advances, we explore innovative therapies emerging from cutting-edge research: nanotechnology-based drug delivery systems capable of navigating the blood-brain barrier, gene-editing tools like CRISPR designed to correct harmful genetic variants, and stem cell strategies that not only replace lost neurons but foster neuroprotective environments. Pharmacogenomics is reshaping treatment personalization, enabling tailored therapies that align with individual genetic profiles, while molecular diagnostics and biomarkers are ushering in an era of early, precise disease detection. Furthermore, novel perspectives on the gut-brain axis are sparking interest as mounting evidence suggests that microbiome modulation may play a role in reducing neuroinflammatory responses linked to neurodegenerative progression. Taken together, these advances signal a shift toward a comprehensive, personalized approach that could transform neurodegenerative care. By integrating molecular insights and innovative therapeutic techniques, this review offers a forward-looking perspective on a future where treatments aim not just to manage symptoms but to fundamentally alter disease progression, presenting renewed hope for improved patient outcomes.}, } @article {pmid39684308, year = {2024}, author = {Ścibior, A and Llopis, J and Dobrakowski, PP and Męcik-Kronenberg, T}, title = {Magnesium (Mg) and Neurodegeneration: A Comprehensive Overview of Studies on Mg Levels in Biological Specimens in Humans Affected Some Neurodegenerative Disorders with an Update on Therapy and Clinical Trials Supplemented with Selected Animal Studies.}, journal = {International journal of molecular sciences}, volume = {25}, number = {23}, pages = {}, pmid = {39684308}, issn = {1422-0067}, mesh = {Humans ; *Magnesium/therapeutic use ; Animals ; *Neurodegenerative Diseases/drug therapy ; Amyotrophic Lateral Sclerosis/drug therapy/metabolism ; Clinical Trials as Topic ; Disease Models, Animal ; Neuroprotective Agents/therapeutic use/pharmacology ; Parkinson Disease/drug therapy/metabolism ; Alzheimer Disease/drug therapy/metabolism ; }, abstract = {Neurodegenerative diseases, characterized by neuron loss, are a group of neurological disorders that adversely affect the lives of millions of people worldwide. Although several medicines have been approved for managing neurodegenerative diseases, new therapies allowing for a significant slowdown in the progression of neurodegenerative syndromes are constantly being sought. Magnesium (Mg), a crucial mineral necessary for the functioning of organisms, is important to normal central nervous system (CNS) activity. Although the effects of this bioelement on the CNS are relatively well recognized, its role in the pathophysiology of neurological disorders in humans is not yet well characterized. Therefore, the main goal of this review is to collect data about a possible association between Mg and neurodegenerative disorders such as Alzheimer's disease (AD), Parkinson's Disease (PD), and Amyotrophic lateral sclerosis (ALS) in humans. Hence, the levels of Mg in blood, cerebrospinal fluid (CSF), urine, and hair from subjects with AD, PD, and ALS are compiled to detect possible variations in the levels of this mineral in the biological specimens of people with neurodegenerative illnesses. Additionally, the findings from an animal model are summarized to offer the reader a deeper insight into studies on Mg in the context of neuroprotection and neurodegeneration. Data provided in the present review indicate that Mg, due to its neuroprotective, antioxidant, anti-inflammatory, and mitochondrial-supportive properties, could be a potential therapeutic agent for AD, PD, and ALS. However, more epidemiological studies with standardized methods of dietary assessment and Mg measurement are necessary to recognize its exact role in neurodegenerative disorders. Moreover, extensive well-designed clinical trials are also needed to establish definitive therapeutic protocols and optimal dosages, and to ensure long-term safety of this mineral supplementation in AD, PD, and ALS patients.}, } @article {pmid39684197, year = {2024}, author = {García-González, N and Gonçalves-Sánchez, J and Gómez-Nieto, R and Gonçalves-Estella, JM and López, DE}, title = {Advances and Challenges in Gene Therapy for Neurodegenerative Diseases: A Systematic Review.}, journal = {International journal of molecular sciences}, volume = {25}, number = {23}, pages = {}, pmid = {39684197}, issn = {1422-0067}, mesh = {Humans ; *Genetic Therapy/methods ; *Neurodegenerative Diseases/therapy/genetics ; Animals ; Amyotrophic Lateral Sclerosis/therapy/genetics ; }, abstract = {This review explores recent advancements in gene therapy as a potential treatment for neurodegenerative diseases, focusing on intervention mechanisms, administration routes, and associated limitations. Following the PRISMA procedure guidelines, we systematically analyzed studies published since 2020 using the PICO framework to derive reliable conclusions. The efficacy of various gene therapies was evaluated for Parkinson's disease (n = 12), spinal muscular atrophy (n = 8), Huntington's disease (n = 3), Alzheimer's disease (n = 3), and amyotrophic lateral sclerosis (n = 6). For each condition, we assessed the therapeutic approach, curative or disease-modifying potential, delivery methods, advantages, drawbacks, and side effects. Results indicate that gene therapies targeting specific genes are particularly effective in monogenic disorders, with promising clinical outcomes expected in the near future. In contrast, in polygenic diseases, therapies primarily aim to promote cell survival. A major challenge remains: the translation of animal model success to human clinical application. Additionally, while intracerebral delivery methods enhance therapeutic efficacy, they are highly invasive. Despite these hurdles, gene therapy represents a promising frontier in the treatment of neurodegenerative diseases, underscoring the need for continued research to refine and personalize treatments for each condition.}, } @article {pmid39682764, year = {2024}, author = {Huang, R and Xia, H and Lin, W and Wang, Z and Li, L and Deng, J and Ye, T and Li, Z and Yang, Y and Huang, Y}, title = {Riluzole Reverses Blood-Testis Barrier Loss to Rescue Chemotherapy-Induced Male Infertility by Binding to TRPC.}, journal = {Cells}, volume = {13}, number = {23}, pages = {}, pmid = {39682764}, issn = {2073-4409}, support = {No. U22A20277, 32170865, and 82071634//National Natural Science Foundation of China/ ; No. 2022A1515012178//Natural Science Foundation of Guangdong Province/ ; No. 202103030003//Guangzhou Key R&D Program/ ; No.2022B1111080007//Kea-Area Research and Development Program of Guangdong Province/ ; }, mesh = {Male ; *Riluzole/pharmacology/therapeutic use ; Animals ; *Blood-Testis Barrier/drug effects/metabolism ; *Infertility, Male/chemically induced/drug therapy/pathology ; Mice ; TRPC Cation Channels/metabolism ; Busulfan/pharmacology/adverse effects ; Antineoplastic Agents/pharmacology/adverse effects ; Mice, Inbred C57BL ; Molecular Docking Simulation ; Protein Binding/drug effects ; }, abstract = {Cancer treatments, including cytotoxic therapy, often result in male infertility, necessitating the development of safe and effective strategies to preserve male reproductive potential during chemotherapy. Notably, our study uncovers the potential of repurposing riluzole, an FDA-approved drug for amyotrophic lateral sclerosis (ALS), in enhancing spermatogenesis. Hence, this research aims to explore the feasibility of utilizing riluzole to alleviate male infertility induced by busulfan (BSF), a commonly used chemotherapy drug. We established a BSF-induced oligospermia model in 4-week-old male mice and found that riluzole could effectively counter the detrimental effects of BSF on sperm production in mice with oligospermia. By restoring blood-testis barrier (BTB) functionality, riluzole improves sperm quality and reduces testicular atrophy. Through transcriptomic and molecular docking analyses, we identify transient receptor potential canonical subfamily member 5 (TRPC5) as a potential target for riluzole-mediated regulation of blood-testis barrier function. These findings propose riluzole as a promising therapeutic option for chemotherapy-induced male infertility, thereby addressing the fertility challenges associated with cancer treatments. Moreover, repurposing riluzole could streamline the drug development process, providing a cost-effective approach with reduced risk compared to developing entirely new drugs.}, } @article {pmid39681722, year = {2025}, author = {Weiner, HL}, title = {Immune mechanisms and shared immune targets in neurodegenerative diseases.}, journal = {Nature reviews. Neurology}, volume = {21}, number = {2}, pages = {67-85}, pmid = {39681722}, issn = {1759-4766}, mesh = {Humans ; *Neurodegenerative Diseases/immunology/therapy ; Animals ; Microglia/immunology ; *Immunotherapy/methods ; Multiple Sclerosis/immunology ; Amyotrophic Lateral Sclerosis/immunology ; }, abstract = {The immune system plays a major part in neurodegenerative diseases. In some, such as multiple sclerosis, it is the primary driver of the disease. In others, such as Alzheimer disease, amyotrophic lateral sclerosis and Parkinson disease, it has an amplifying role. Immunotherapeutic approaches that target the adaptive and innate immune systems are being explored for the treatment of almost all neurological diseases, and the targets and approaches are often common across diseases. Microglia are the primary immune cells in the brain that contribute to disease pathogenesis, and are consequently a common immune target for therapy. Other therapeutic approaches target components of the peripheral immune system, such as regulatory T cells and monocytes, which in turn act within the CNS. This Review considers in detail how microglia, monocytes and T cells contribute to the pathogenesis of multiple sclerosis, Alzheimer disease, amyotrophic lateral sclerosis and Parkinson disease, and their potential as shared therapeutic targets across these diseases. The microbiome is also highlighted as an emerging therapeutic target that indirectly modulates the immune system. Therapeutic approaches being developed to target immune function in neurodegenerative diseases are discussed, highlighting how immune-based approaches developed to treat one disease could be applicable to multiple other neurological diseases.}, } @article {pmid39681698, year = {2025}, author = {Aschemacher, NA and Siano, ÁS and Teglia, CM and Goicoechea, HC}, title = {Development, optimization and comparison of solid-liquid and liquid-liquid microextraction for the determination of four flavonols in Schinus molle L. using high-performance liquid chromatography coupled with second-order data modeling.}, journal = {Analytical and bioanalytical chemistry}, volume = {417}, number = {7}, pages = {1381-1392}, pmid = {39681698}, issn = {1618-2650}, support = {PICT 2020-0304//Fondo para la Investigación Científica y Tecnológica/ ; }, mesh = {Chromatography, High Pressure Liquid/methods ; *Liquid Phase Microextraction/methods ; *Flavonols/analysis/isolation & purification ; Limit of Detection ; Flavonoids/analysis ; *Solid Phase Microextraction/methods ; Quercetin/analysis/analogs & derivatives ; Plant Extracts/chemistry/analysis ; Schinus ; }, abstract = {Flavonoids are particularly interesting because they have a broad spectrum of biological effects, including antioxidant and free radical scavenging activities. In this work, solid-liquid microextraction and dispersive liquid-liquid microextraction enhanced by ultrasound were developed and compared with the conventional method (Soxhlet extraction) to optimize the extraction of four flavonoids: rutin, quercitrin, quercetin, and myricetin in samples of Schinus molle (Aguaribay). During the development of the analytical method, different chemometric tools were used to optimize the microextraction procedure. In addition, an analytical method based on high-performance liquid chromatography with diode array detector (HPLC-DAD) and second order calibration using multivariate curve resolution-alternating least square (MCR-ALS) is presented to quantify the flavonoids with limits of quantification between 0.011 and 0.082 µg mL[-1]. Finally, solid-liquid microextraction using 4.00 mL water/ethanol (54.3:45.7%), 14 s vortex, and 45 min was selected as the most suitable method due to its high recovery rate and environmental friendliness (with a greenness score of 0.78). After the optimization step, the concentrations found in the plant samples were 1825.3, 632.6, 110.2, and 18.9 µg g[-1] for rutin, quercitrin, quercetin, and myricetin, respectively. The present work is the first achievement of simultaneously determining these four analytes with exceptional sensitivity, demonstrating lower LOQs compared to previous reports.}, } @article {pmid39680524, year = {2024}, author = {Rocha, PS and Bento, N and Folgado, D and Carreiro, AV and Santos, MO and de Carvalho, M and Miranda, B}, title = {Evaluation of smartphone-based cough data in amyotrophic lateral sclerosis as a potential predictor of functional disability.}, journal = {PloS one}, volume = {19}, number = {12}, pages = {e0301734}, pmid = {39680524}, issn = {1932-6203}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology/complications/diagnosis ; *Cough/physiopathology ; Male ; Female ; *Smartphone ; Middle Aged ; Case-Control Studies ; Aged ; Cross-Sectional Studies ; Support Vector Machine ; Adult ; }, abstract = {OBJECTIVES: Cough dysfunction is a feature of patients with amyotrophic lateral sclerosis (ALS). The cough sounds carry information about the respiratory system and bulbar involvement. Our goal was to explore the association between cough sound characteristics and the respiratory and bulbar functions in ALS.

METHODS: This was a single-center, cross-sectional, and case-control study. On-demand coughs from ALS patients and healthy controls were collected with a smartphone. A total of 31 sound features were extracted for each cough recording using time-frequency signal processing analysis. Logistic regression was applied to test the differences between patients and controls, and in patients with bulbar and respiratory impairment. Support vector machines (SVM) were employed to estimate the accuracy of classifying between patients and controls and between patients with bulbar and respiratory impairment. Multiple linear regressions were applied to examine correlations between cough sound features and clinical variables.

RESULTS: Sixty ALS patients (28 with bulbar dysfunction, and 25 with respiratory dysfunction) and forty age- and gender-matched controls were recruited. Our results revealed clear differences between patients and controls, particularly within the frequency-related group of features (AUC 0.85, CI 0.79-0.91). Similar results were observed when comparing patients with and without bulbar dysfunction. Sound features related to intensity displayed the strongest correlation with disease severity, and were the most significant in distinguishing patients with and without respiratory dysfunction.

DISCUSSION: We found a good relationship between specific cough sound features and clinical variables related to ALS functional disability. The findings relate well with some expected impact from ALS on both respiratory and bulbar contributions to the physiology of cough. Finally, our approach could be relevant for clinical practice, and it also facilitates home-based data collection.}, } @article {pmid39680215, year = {2024}, author = {Wu, H and Erenay, FS and Özaltın, OY and Dalgıç, ÖO and Sır, MY and He, QM and Crum, BA and Pasupathy, KS and , }, title = {Prognostic factors affecting ALS progression through disease tollgates.}, journal = {Journal of neurology}, volume = {272}, number = {1}, pages = {69}, pmid = {39680215}, issn = {1432-1459}, support = {2018-06596//NSERC (Natural Sciences and Engineering Research Council of Canada)/ ; 2017-04001//NSERC (Natural Sciences and Engineering Research Council of Canada)/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology/diagnosis ; *Disease Progression ; Male ; Female ; Prognosis ; Middle Aged ; Aged ; }, abstract = {BACKGROUND AND OBJECTIVES: Understanding factors affecting the timing of critical clinical events in ALS progression.

METHODS: We captured ALS progression based on the timing of critical events (tollgates), by augmenting 6366 patients' data from the PRO-ACT database with tollgate-passed information using classification. Time trajectories of passing ALS tollgates after the first visit were derived using Kaplan-Meier analyses. The significant prognostic factors were found using log-rank tests. Decision-tree-based classifications identified significant ALS phenotypes characterized by the list of body segments involved at the first visit.

RESULTS: Standard (e.g., gender and onset type) and tollgate-related (phenotype and initial tollgate level) prognostic factors affect the timing of ALS tollgates. For instance, by the third year after the first visit, 80-100% of bulbar-onset patients vs. 43-48% of limb-onset patients, and 65-73% of females vs. 42-49% of males lost the ability to talk and started using a feeding tube. Compared to the standard factors, tollgate-related factors had a stronger effect on ALS progression. The initial impairment level significantly impacted subsequent ALS progression in a segment while affected segment combinations further characterized progression speed. For instance, patients with normal speech (Tollgate Level 0) at the first visit had less than a 10% likelihood of losing speech within a year, while for patients with Tollgate Level 1 (affected speech), this likelihood varied between 23 and 53% based on additional segment (leg) involvement.

CONCLUSIONS: Tollgate- and phenotype-related factors have a strong effect on the timing of ALS tollgates. All factors should be jointly considered to better characterize patient groups with different progression aggressiveness.}, } @article {pmid39679928, year = {2024}, author = {Bhattacharjee, T and Vengalil, S and Belur, Y and Atchayaram, N and Ghosh, PK}, title = {Inter-speaker acoustic differences of sustained vowels at varied dysarthria severities for amyotrophic lateral sclerosis.}, journal = {JASA express letters}, volume = {4}, number = {12}, pages = {}, doi = {10.1121/10.0034613}, pmid = {39679928}, issn = {2691-1191}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology ; *Dysarthria/etiology/physiopathology ; *Speech Acoustics ; Male ; Female ; Middle Aged ; Aged ; Severity of Illness Index ; Phonetics ; }, abstract = {We study inter-speaker acoustic differences during sustained vowel utterances at varied severities of Amyotrophic Lateral Sclerosis-induced dysarthria. Among source attributes, jitter and standard deviation of fundamental frequency exhibit enhanced inter-speaker differences among patients than healthy controls (HCs) at all severity levels. Though inter-speaker differences in vocal tract filter attributes at most severity levels are higher than those among HCs for close vowels /i/ and /u/, these are comparable with or lower than those among HCs for the relatively more open vowels /a/ and /o/. The differences typically increase with severity except for a few parameters for /a/ and /i/.}, } @article {pmid39679063, year = {2024}, author = {Kodavati, M and Hegde, ML}, title = {A Commentary on Mitochondrial Dysfunction and Compromised DNA Repair in Neurodegeneration: The Emerging Role of FUS in ALS.}, journal = {Neuroscience insights}, volume = {19}, number = {}, pages = {26331055241305151}, pmid = {39679063}, issn = {2633-1055}, support = {R01 NS088645/NS/NINDS NIH HHS/United States ; R01 NS094535/NS/NINDS NIH HHS/United States ; R03 AG064266/AG/NIA NIH HHS/United States ; RF1 NS112719/NS/NINDS NIH HHS/United States ; }, abstract = {Mitochondrial dysfunction plays a pivotal role in the progression of neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), Alzheimer's, and Parkinson's disease. Recent discoveries have highlighted the involvement of DNA damage and repair processes, particularly mitochondrial DNA (mtDNA) damage, in these conditions. This commentary reflects on our recent findings, demonstrating the RNA/DNA binding protein fused in sarcoma (FUS)'s crucial role in maintaining mtDNA integrity through interactions with mitochondrial DNA ligase IIIα (mtLig3). Our studies provide direct evidence of increased mtDNA damage in ALS-linked FUS mutant cells, emphasizing the potential of targeting DNA repair pathways to mitigate neurodegeneration. Furthermore, the restoration of mitochondrial function through targeted expression of human DNA ligase 1 (Lig1) in FUS mutant models showcases the therapeutic promise of DNA repair mechanisms in neurodegenerative diseases. These insights offer new molecular understanding and open up future avenues for therapeutic interventions, particularly in FUS-associated ALS and related disorders.}, } @article {pmid39678608, year = {2024}, author = {Dong, F}, title = {Bioinformatic materials science reconsidered.}, journal = {American journal of translational research}, volume = {16}, number = {11}, pages = {7200-7204}, pmid = {39678608}, issn = {1943-8141}, abstract = {Bioinformatic materials science integrates medical science, materials science, informatics, and other disciplines, aiming to maintain the balance of tissues and organs in the human body. This paper explores the relationship between structural information and the structures synthesized through regulated gene expression. Specifically, it describes the transformation of information into substances via biological structural systems, using mathematical formulas to develop bioinformatic materials. These materials have applications in medical treatments, functional foods for preventive healthcare, and cosmetic products for health maintenance. Notably, bioinformatic materials have been applied in treating acromegaly, a rare and life-threatening disease of unknown etiology, and have improved the neurofilament light chain (NFL) index and typical symptoms of Amyotrophic Lateral Sclerosis (ALS). In summary, bioinformatic materials science holds potential for enhancing human health and contributing to advances in medicine.}, } @article {pmid39678458, year = {2024}, author = {Sulek, A}, title = {Secretome - the role of extracellular vesicles in the pathogenesis and therapy of neurodegenerative diseases.}, journal = {Postepy psychiatrii neurologii}, volume = {33}, number = {3}, pages = {147-162}, pmid = {39678458}, issn = {2720-5371}, abstract = {PURPOSE: Extracellular vesicles are the subject of many studies in various medical specialties. Their role in neurodegenerative diseases is increasing and they worth introducing in more detail.

METHODS: This review was performed following an electronic search of the database PubMed/Medline and Web of Science for English-language articles between 2010 and 2024 in the fields of medicine, molecular biology, and biochemistry. Keywords searches included combinations of the following terms: "extracellular vesicles" OR "exosomes" AND "neurodeg*" AND "microRNA" OR "miRNA" AND "AD" OR "PD" OR "ALS" OR "HD". Articles had to be original work or reviews.

RESULTS: The classification of extracellular vesicles is based on their size or origin. Their content is of key importance in communication between cells and can be treated as a physiological determinant of the normal or pathological condition of a body. The cargo transported in the extracellular space and over longer distances in various body fluids is diversified and may be nucleic acids (DNA, RNA, miRNA) as well as proteins and lipids, and, in the case of apoptotic bodies also a cell's organelles. Exosomes are the most thoroughly studied extracellular vesicles and the most often considered for therapeutic applications. Vesicles carrying biological substances in the body perform three basic functions: participation in a pathological mechanism, a biomarker role that also has diagnostic and prognostic functions, and a role in therapeutic activities. In the case of neurodegenerative diseases, it appears that extracellular vesicles can transport misfolded proteins, initiating pathological processes in previously normal cells.

CONCLUSIONS: The transport of various substances enclosed in vesicles seems to be very promising in therapeutic prospects in various diseases, and the possibility of their crossing the blood-brain barrier particularly indicates diseases of the central nervous system. Despite many years of research on extracellular vesicles in the context of neurodegenerative diseases, their practical use is currently limited to studies on animal and cellular models, and their practical application in clinical trials in neurodegenerative diseases is to date extremely rare.}, } @article {pmid39678223, year = {2025}, author = {Banos, M and Preuilh, A and Pradat, PF and Lackmy-Vallée, A and Marchand-Pauvert, V}, title = {Exercises and Brain Stimulation to Preserve Function in Amyotrophic Lateral Sclerosis: A Systematic Review and Meta-Analysis.}, journal = {Neurology. Clinical practice}, volume = {15}, number = {1}, pages = {e200408}, pmid = {39678223}, issn = {2163-0402}, abstract = {BACKGROUND AND OBJECTIVES: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease leading to the loss of motor function and muscle strength. Nonpharmacologic neuromodulative therapeutic approaches such as active exercise may contribute to preserve motor functions in ALS, but this hypothesis remains debated. The present meta-analysis first aimed to evaluate the effect of active exercise on function and muscle strength preservation. Moreover, since the responsiveness to induced neuroplasticity of patients with ALS is being discussed, the second objective was to review the analogous effects of noninvasive brain stimulation (NIBS).

METHODS: Following PRISMA guidelines, we systematically reviewed PubMed, CENTRAL, NIH PMC, PEDro, ScienceDirect, and Web of Science databases from the period between January 10 and July 1, 2023. Criteria limited inclusion to randomized controlled trials comparing active exercise (aerobic or resistance) with usual care or NIBS with sham. The primary outcome was assessed based on functional assessment scores reported on validated clinical scales, and the secondary outcome analysis included muscle strength and neurophysiologic changes. Methodologic quality of the selected studies was assessed using the Physiotherapy Evidence-Based (PEDro) scale. Relative risk (RR) and heterogeneity (I[2]) were calculated with Revman software, and evidence quality was estimated by the GRADE quality scale.

RESULTS: Thirteen studies were included. Analysis involved 393 patients among whom 164 underwent active exercise and 155 received usual care, 41 received NIBS and 33 underwent sham stimulations. The nature of active exercise was consistent across studies but varied in frequency. NIBS parameters were consistent for stimulation sites and session frequency. Function was significantly preserved in 5 of 9 studies on active exercise and 2 of 4 NIBS trials. Meta-analysis on functional scales indicated a moderate quality of evidence for the effectiveness of active exercises (RR = 0.61 [0.18, 1.04] with I[2] = 69%) compared with usual care and very low quality of evidence for NIBS (RR = -1.41 [-0.44, 3.26] with I[2] = 89%). Only 1 NIBS study revealed neuroplastic changes in the brain.

DISCUSSION: Active exercise likely slows functional loss in ALS, but the effects of NIBS need further investigation to support their neuroprotective effectiveness. Moreover, both interventions require further neurophysiologic investigation to elucidate ALS neuroplasticity.

This review has been registered in PROSPERO (CRD42023408121).}, } @article {pmid39678056, year = {2024}, author = {Baslo, SA and Şirin, NG and Orhan, EK and Baslo, MB and Öge, AE}, title = {Selective Muscle Involvement in Amyotrophic Lateral Sclerosis: Evidence Inferred from the Point of Motor Unit Firing Rates.}, journal = {Noro psikiyatri arsivi}, volume = {61}, number = {4}, pages = {296-305}, pmid = {39678056}, issn = {1300-0667}, abstract = {INTRODUCTION: The aim of the study is to determine the role of upper motor neuron (UMN) or lower motor neuron (LMN) dysfunction as the primary initiator of distal-proximal and lateral-medial gradients of muscle involvement in amyotrophic lateral sclerosis (ALS).

METHODS: Concentric needle electromyography recordings were performed in deltoid, abductor digiti minimi, and first dorsal interosseous (FDI) muscles in patients with ALS and controls during slight voluntary contraction needed to activate two motor units (MU). Five motor unit potential (MUP) pairs were recorded from each muscle. Motor unit potential analyses were performed offline using Multi-MUP analysis program. Quantitative MUP parameters, MU firing rate (FR), FR variability (FRV), and mean consecutive difference (MCD) were calculated. Motor-evoked potentials and the triple stimulation technique (TST) were performed to evaluate UMN involvement.

RESULTS: Twenty patients with ALS along with 20 age and sex-matched healthy volunteers were enrolled. Quantitative MUP parameters compatible with denervation and reinnervation were found in patients with ALS, who also showed higher FR, FRV, and MCD values, most prominently in FDI. First dorsal interosseous FRV was lower in patients with abnormal central motor conduction time (CMCT). Firing rate and FRV were negatively correlated with CMCT, but not with TST.

CONCLUSION: Distal limb muscles, particularly FDI, revealed more prominent FR abnormalities in patients with ALS in parallel with the distal-proximal and lateral-medial gradients of the selective muscle involvement pattern which seems predominantly to be correlated with LMN dysfunction. Reduced FRV may be associated with the presence of UMN dysfunction in ALS.}, } @article {pmid39678053, year = {2024}, author = {Finsterer, J and Mehri, S}, title = {The Causality Spectrum of Dropped Head Syndrome is Broad and Includes Myopathy, Neurodegenerative Disorders, and Varia.}, journal = {Noro psikiyatri arsivi}, volume = {61}, number = {4}, pages = {382-383}, pmid = {39678053}, issn = {1300-0667}, abstract = {Dropped head syndrome is a common complication of various neurological disorders. Most commonly, dropped head syndrome is due to primary or secondary myopathy. However, neurodegenerative diseases and various other conditions can also be complicated by dropped head syndrome. Among the primary myopathies, dropped head occurs most commonly in association with mitochondrial disorders, congenital myasthenic syndrome, and axial myopathies. Among the secondary myopathies, dropped occurs most commonly in association with inflammatory myopathies. Myasthenia is the most common transmission disorder associated with dropped head syndrome. The neurodegenerative disorder most commonly associated with dropped head syndrome is Parkinson syndrome. The diagnosis and treatment of dropped head syndrome from any cause requires a multidisciplinary approach. Outcome varies considerably but early diagnosis and early treatment are associated with a more favourable outcome.}, } @article {pmid39677679, year = {2024}, author = {Chen, L and Smith, M and Roe, DR and Miranda-Quintana, RA}, title = {Extended Quality (eQual): Radial threshold clustering based on n-ary similarity.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {39677679}, issn = {2692-8205}, support = {R35 GM150620/GM/NIGMS NIH HHS/United States ; }, abstract = {We are transforming Radial Threshold Clustering (RTC), an O (N 2) algorithm, into Extended Quality Clustering, an O (N) algorithm with several novel features. Daura et al's RTC algorithm is a partitioning clustering algorithm that groups similar frames together based on their similarity to the seed configuration. Two current issues with RTC is that it scales as O (N 2) making it inefficient at high frame counts, and the clustering results are dependent on the order of the input frames. To address the first issue, we have increased the speed of the seed selection by using k -means++ to select the seeds of the available frames. To address the second issue and make the results invariant with respect to frame ordering, whenever there is a tie in the most populated cluster, the densest and most compact cluster is chosen using the extended similarity indices. The new algorithm is able to cluster in linear time and produce more compact and separate clusters.}, } @article {pmid39677629, year = {2024}, author = {Park, S and Park, SK and Liebman, SW}, title = {A model of inborn metabolism errors associated with adenine amyloid-like fiber formation reduces TDP-43 aggregation and toxicity in yeast.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2024.12.03.626668}, pmid = {39677629}, issn = {2692-8205}, abstract = {TDP-43 is linked to human diseases such as amyotrophic lateral sclerosis (ALS) and frontotemporal degeneration (FTD). Expression of TDP-43 in yeast is known to be toxic, cause cells to elongate, form liquid-like aggregates, and inhibit autophagy and TOROID formation. Here, we used the apt1Δ aah1Δ yeast model of disorders of inborn errors of metabolism, previously shown to lead to intracellular adenine accumulation and adenine amyloid-like fiber formation, to explore interactions with TDP-43. Results show that the double deletion shifts the TDP-43 aggregates from a liquid-like, toward a more amyloid-like, state. At the same time the deletions reduce TDP-43's effects on toxicity, cell morphology, autophagy, and TOROID formation without affecting the level of TDP-43. This suggests that the liquid-like and not amyloid-like TDP-43 aggregates are responsible for the deleterious effects in yeast. How the apt1Δ aah1Δ deletions alter TDP-43 aggregate formation is not clear. Possibly, it results from adenine/TDP-43 fiber interactions as seen for other heterologous fibers. The work offers new insights into the potential interactions between metabolite-based amyloids and pathological protein aggregates, with broad implications for understanding protein misfolding diseases.}, } @article {pmid39677625, year = {2024}, author = {Li, A and Dong, L and Li, X and Yi, J and Ma, J and Zhou, J}, title = {ALDH3A1-mediated detoxification of reactive aldehydes contributes to distinct muscle responses to denervation and Amyotrophic Lateral Sclerosis progression.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {39677625}, issn = {2692-8205}, support = {R01 AG071676/AG/NIA NIH HHS/United States ; R01 NS105621/NS/NINDS NIH HHS/United States ; R01 NS129219/NS/NINDS NIH HHS/United States ; }, abstract = {Different muscles exhibit varied susceptibility to degeneration in Amyotrophic Lateral Sclerosis (ALS), a fatal neuromuscular disorder. Extraocular muscles (EOMs) are particularly resistant to ALS progression and exploring the underlying molecular nature may deliver great therapeutic value. Reactive aldehyde 4-hydroxynonenal (HNE) is implicated in ALS pathogenesis and ALDH3A1 is an inactivation-resistant intracellular detoxifier of 4-HNE protecting eyes against UV-induced oxidative stress. Here we detected prominently higher levels of ALDH3A1 in mouse EOMs than other muscles under normal physiological conditions. In an ALS mouse model (hSOD1[G93A]) reaching end-stage, ALDH3A1 expression was sustained at high level in EOMs, whereas substantial upregulation of ALDH3A1 occurred in soleus and diaphragm. The upregulation was less pronounced in extensor digitorum longus (EDL) muscle, which endured the most severe pathological remodeling as demonstrated by unparalleled upregulation of a denervation marker ANKRD1 expression. Interestingly, sciatic nerve transection in wildtype mice induced ALDH3A1 and ANKRD1 expression in an inverse manner over muscle type and time. Adeno-associated virus enforced overexpression of ALDH3A1 protected myotubes from 4-HNE-induced DNA fragmentation, plasma membrane leakage and restored MG53-mediated membrane repair. Our data indicate that ALDH3A1 may contribute to distinct muscle resistance to ALS through detoxifying reactive aldehydes.}, } @article {pmid39676614, year = {2025}, author = {Roscoe, S and Allen, SP and McDermott, C and Stavroulakis, T}, title = {Exploring the role of anthropometric measurements to assess nutritional status in amyotrophic lateral sclerosis: a longitudinal prospective cohort study.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {26}, number = {3-4}, pages = {225-238}, pmid = {39676614}, issn = {2167-9223}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology/diagnosis ; Male ; Female ; Middle Aged ; *Nutritional Status/physiology ; *Anthropometry/methods ; Aged ; Longitudinal Studies ; Prospective Studies ; Adult ; Body Mass Index ; Cohort Studies ; Body Weight/physiology ; Skinfold Thickness ; }, abstract = {OBJECTIVE: To observe longitudinal correlations between limb anthropometry against weight, BMI and functional decline in patients with amyotrophic lateral sclerosis.

METHODS: A longitudinal, prospective, cohort study was undertaken. Four consecutive measurements of weight, height, triceps skinfold thickness (TSF), mid-upper arm (MUAC) and calf circumferences were collected at three-monthly intervals. Fat- and lean body mass were estimated using measurements of TSF and derivations of arm muscle area, respectively. Correlation analyses indicated associations between anthropometric assessments and functional decline (ALSFRS-R). Longitudinal changes were assessed using repeated measures analyses.

RESULTS: Data from 18 participants was analyzed. At enrollment, weight positively correlated with MUAC (n = 17, p = 0.0001), arm muscle area (n = 17, p = 0.04) and calf circumference (n = 17, p < 0.0001). The ALSFRS-R score negatively correlated with weight (n = 17, p = 0.03), MUAC (n = 18, p = 0.01), TSF (n = 18, p = 0.04), and calf circumference (n = 18, p = 0.003). Function significantly declined by a difference of 6.3 points per month (p = 0.009). A positive correlation was observed between the changes in weight and calf circumference over nine months (r = 0.70, p = 0.02, n = 10).

CONCLUSION: Limb anthropometric measurements may be surrogate indicators of weight and BMI; TSF may be a practical, reliable indicator of fat mass, whilst changes in calf circumference may be alternatively used to monitor changes in nutritional status in the clinic.}, } @article {pmid39674407, year = {2025}, author = {Xue, S and Bao, W and Lyu, J and Wang, C and Zhang, Y and Li, H and Chen, D and Lu, Y}, title = {In vitro nephrotoxicity and structure-toxicity relationships of eight natural aristolactams.}, journal = {Toxicon : official journal of the International Society on Toxinology}, volume = {254}, number = {}, pages = {108214}, doi = {10.1016/j.toxicon.2024.108214}, pmid = {39674407}, issn = {1879-3150}, mesh = {Humans ; Structure-Activity Relationship ; *Aristolochic Acids/toxicity/chemistry ; Reactive Oxygen Species/metabolism ; Cell Survival/drug effects ; Cell Line ; Epithelial Cells/drug effects ; Transforming Growth Factor beta1/metabolism ; Hepatitis A Virus Cellular Receptor 1/metabolism ; }, abstract = {The structural similarity between aristolactams (ALs) and aristolochic acids (AAs) raises constant concerns about the safety of ALs-containing plants. Natural ALs are distributed more extensively than AAs, leading to a higher risk of ALs exposure in daily consumption. This study aimed to evaluate and compare the in vitro nephrotoxicity on human renal tubular epithelial cells (HK-2 cells) of eight natural ALs with different substituents on the phenanthrene ring and amide ring, including aristolactam Ⅰ (AL Ⅰ), AL BⅡ, velutinam, AL AⅡ, sauristolactam, AL AⅠa, AL FⅠ and N-methyl piperolactam A. Their IC50 values of cell viability were tested by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and enzyme-linked immunosorbent assay (ELISA) was used to determine the levels of kidney injury molecule-1 (KIM-1), transforming growth factor-β1 (TGF-β1) and fibronectin (FN). The reactive oxygen species (ROS) assay was used to detect the intracellular oxidative stress level. The results showed that the eight ALs all had specific nephrotoxicity on HK-2 cells. Particularly, AL Ⅰ, AL BⅡ and velutinam exhibited more potent cytotoxicity on HK-2 cells (IC50 = 2.49-2.78 μM) than the other five ALs (IC50 = 12.33-43.84 μM). The structure-toxicity relationships indicated that both methylenedioxy (-OCH2O-) and methoxy (-OCH3) were positively contributing functional groups of ALs on nephrotoxicity, while the hydroxy group (-OH) and methyl substitution on nitrogen (N-CH3) accounted for a detrimental effect conversely. Consistent with this structure-toxicity relationship, the eight ALs increased KIM-1 levels in the same trend as their cytotoxicity at the same concentration of 2.5 μg/mL, associating with different levels of ROS generation. And the four most toxic ALs, AL Ⅰ, AL BⅡ, velutinam and AL AⅡ, could also induce fibrosis by increasing TGF-β1 and FN levels.}, } @article {pmid39674307, year = {2025}, author = {Pistolesi, A and Ranieri, G and Calvani, M and Guasti, D and Chiarugi, A and Buonvicino, D}, title = {Microglial suppression by myeloperoxidase inhibitor does not delay neurodegeneration in a mouse model of progressive multiple sclerosis.}, journal = {Experimental neurology}, volume = {385}, number = {}, pages = {115095}, doi = {10.1016/j.expneurol.2024.115095}, pmid = {39674307}, issn = {1090-2430}, mesh = {Animals ; Mice ; *Microglia/drug effects ; Disease Models, Animal ; *Peroxidase/antagonists & inhibitors/metabolism ; Mice, Inbred NOD ; Female ; *Multiple Sclerosis, Chronic Progressive/pathology/drug therapy ; Disease Progression ; Reactive Oxygen Species/metabolism ; *Propionates/pharmacology/therapeutic use ; *Enzyme Inhibitors/therapeutic use/pharmacology ; Mitochondria/drug effects/metabolism ; *Nerve Degeneration/pathology/drug therapy ; Spinal Cord/pathology/drug effects ; Aminopyridines ; Pyrroles ; }, abstract = {Drugs able to efficiently counteract the progression of multiple sclerosis (MS) are still an unmet need. Numerous preclinical evidence indicates that reactive oxygen-generating enzyme myeloperoxidase (MPO), expressed by neutrophils and microglia, might play a key role in neurodegenerative disorders. Then, the MPO inhibition has been evaluated in clinical trials in Parkinson's and multiple system atrophy patients, and a clinical trial for the treatment of amyotrophic lateral sclerosis is underway. The effects of MPO inhibition on MS patients have not yet been explored. In the present study, by adopting the NOD mouse model of progressive MS (PMS), we evaluated the pharmacological effects of the MPO inhibitor verdiperstat (also known as AZD3241) on functional, immune, and mitochondrial parameters during disease evolution. We found that daily treatment with verdiperstat did not affect the pattern of progression as well as survival, despite its ability to reduce mitochondrial reactive oxygen species and microglia activation in the spinal cord of immunized mice. Remarkably, verdiperstat did not affect adaptive immunity, neutrophils invasion as well as mitochondrial derangement in the spinal cords of immunized mice. Data suggest that microglia suppression is not sufficient to prevent disease evolution, corroborating the hypothesis that immune-independent components drive neurodegeneration in progressive MS.}, } @article {pmid39673573, year = {2024}, author = {Riaz, S and Steinsland, H and Andersen, AZ and Boysen, A and Hanevik, K}, title = {Proportions of IgA antibodies targeting glycosylated epitopes of secreted Escherichia coli mucinase YghJ in initial plasmablast response differ from salivary and intestinally secreted IgA.}, journal = {Medical microbiology and immunology}, volume = {214}, number = {1}, pages = {2}, pmid = {39673573}, issn = {1432-1831}, support = {234364//Research Council of Norway/ ; 234364//Research Council of Norway/ ; 234364//Research Council of Norway/ ; 7041-00220//Innovation Fund Denmark/ ; 7041-00220//Innovation Fund Denmark/ ; }, mesh = {Humans ; Glycosylation ; *Saliva/immunology ; *Epitopes/immunology ; Enterotoxigenic Escherichia coli/immunology ; Escherichia coli Proteins/immunology ; Antibodies, Bacterial/immunology/blood ; Plasma Cells/immunology ; Immunoglobulin A, Secretory/immunology ; Immunoglobulin A/immunology/blood ; Adult ; Male ; Female ; Escherichia coli Infections/immunology ; Young Adult ; }, abstract = {Mucosal infections normally cause an immune response including activation of antigen-specific B cells in regional mucosa-associated lymphoid tissue. After recirculation of plasmablasts, and maturation at mucosal surfaces or bone marrow, plasma cells produce secretory or systemic IgA. It remains uncertain to what extent secretory and systemic IgA share the same target specificities. For vaccine candidate optimization, it is important to know whether IgA targeting of glycosylated epitopes of a protein antigen vary between mucosal and systemic sites. We evaluated glycosylated epitope specificity of systemic and mucosally secreted IgA against YghJ, a potential vaccine candidate antigen secreted by most pathogenic Escherichia coli. IgA from intestinal lavage, saliva, serum, and blood-derived antibody in lymphocyte supernatants (ALS) were collected from 21 volunteers following experimental infection with enterotoxigenic E. coli. Methods for preparing IgA from saliva and ALS were developed, and multiplex bead flow cytometric immunoassays were used to determine levels of IgA targeting natively glycosylated YghJ and estimating what proportion of these antibodies specifically targeted glycosylated epitopes. Following infection, anti-YghJ IgA levels increased substantially for most volunteers across all four specimen types. Target specificity of ALS IgA correlated well with serum IgA, but not with mucosally secreted IgA. Furthermore, glycosylation-specific proportion of salivary IgA was higher than, and did not correlate with, intestinally secreted IgA. These results indicate a new degree of complexity to our understanding of epitope-targeting and tissue specificity of mucosal antibody responses. Our findings also suggest that all features of an intestinal IgA response may not be well reflected in serum, saliva, or ALS, which are commonly used proxy specimens for evaluating intestinal immune responses.}, } @article {pmid39673548, year = {2024}, author = {Alzahrani, AK and Imran, M and Alshrari, AS}, title = {Investigating the impact of SOD1 mutations on amyotrophic lateral sclerosis progression and potential drug repurposing through in silico analysis.}, journal = {Journal of biomolecular structure & dynamics}, volume = {}, number = {}, pages = {1-16}, doi = {10.1080/07391102.2024.2439577}, pmid = {39673548}, issn = {1538-0254}, abstract = {Superoxide dismutase 1 (SOD1) is a vital enzyme responsible for attenuating oxidative stress through its ability to facilitate the dismutation of the superoxide radical into oxygen and hydrogen peroxide. The progressive loss of motor neurons characterize amyotrophic lateral sclerosis (ALS), a crippling neurodegenerative disease that is caused by mutations in the SOD1 gene. In this study, in silico mutational analysis was performed to study the various mutations, the pathogenicity and stability ΔΔG (binding free energy) of the variant of SOD1. x in the protein variant analysis showed a considerable destabilizing effect with a ΔΔG value of -4.2 kcal/mol, signifying a notable impact on protein stability. Molecular dynamics simulations were conducted on both wild-type and C146R mutant SOD1. RMSD profiles indicated that both maintained consistent structural conformation over time. Additionally, virtual screening of 3067 FDA-approved drugs against the mutant SOD1 identified two potential binders, Tucatinib (51039094) and Regorafenib (11167602), which interacted with Leu106, similar to the control drug, Ebselen. Further simulations assessed the dynamic properties of SOD1 in monomeric and dimeric forms while bound to these compounds. 11167602 maintained stable interaction with the monomeric SOD1 mutant, whereas 51039094 and Ebselen dissociated from the monomeric protein's binding site. However, all three compounds were stably bound to the dimeric SOD1. MM/GBSA analysis revealed similar negative binding free energies for 11167602 and 51039094, identifying them as strong binders due to their interaction with Cys111. Experimental validation, including in vitro, cell-based, and in vivo assays are essential to confirm these candidates before advancing to clinical trials.}, } @article {pmid39672239, year = {2025}, author = {Cocozza, G and Busdraghi, LM and Chece, G and Menini, A and Ceccanti, M and Libonati, L and Cambieri, C and Fiorentino, F and Rotili, D and Scavizzi, F and Raspa, M and Aronica, E and Inghilleri, M and Garofalo, S and Limatola, C}, title = {GDF15-GFRAL signaling drives weight loss and lipid metabolism in mouse model of amyotrophic lateral sclerosis.}, journal = {Brain, behavior, and immunity}, volume = {124}, number = {}, pages = {280-293}, doi = {10.1016/j.bbi.2024.12.010}, pmid = {39672239}, issn = {1090-2139}, mesh = {Animals ; *Amyotrophic Lateral Sclerosis/metabolism/physiopathology ; *Growth Differentiation Factor 15/metabolism ; *Weight Loss/physiology ; *Glial Cell Line-Derived Neurotrophic Factor Receptors/metabolism/genetics ; Mice ; Disease Models, Animal ; Signal Transduction/physiology ; *Lipid Metabolism/physiology ; Humans ; Brain Stem/metabolism ; Male ; Mice, Transgenic ; Microglia/metabolism ; Adipose Tissue/metabolism ; Female ; }, abstract = {Weight loss is a common early sign in amyotrophic lateral sclerosis (ALS) patients and negatively correlates with survival. In different cancers and metabolic disorders, high levels of serum growth differentiation factor 15 (GDF15) contribute to a decrease of food intake and body weight, acting through GDNF family receptor alpha-like (GFRAL). Here we report that GDF15 is highly expressed in the peripheral blood of ALS patients and in the hSOD1[G93A] mouse model and that GFRAL is upregulated in the brainstem of hSOD1[G93A] mice. We demonstrate that the localized GFRAL silencing by shRNA in the area postrema/nucleus tractus solitarius of hSOD1[G93A] mice induces weight gain, reduces adipose tissue wasting, ameliorates the motor function and muscle atrophy and prolongs the survival time. We report that microglial cells could be involved in mediating these effects because their depletion with PLX5622 reduces brainstem GDF15 expression, weight loss and the expression of lipolytic genes in adipose tissue. Altogether these results reveal a key role of GDF15-GFRAL signaling in regulating weight loss and the alteration of and lipid metabolism in the early phases of ALS.}, } @article {pmid39672208, year = {2025}, author = {Liu, Y and Wu, L and Peng, W and Mao, X}, title = {Glial polarization in neurological diseases: Molecular mechanisms and therapeutic opportunities.}, journal = {Ageing research reviews}, volume = {104}, number = {}, pages = {102638}, doi = {10.1016/j.arr.2024.102638}, pmid = {39672208}, issn = {1872-9649}, mesh = {Humans ; *Neuroglia/pathology/metabolism/physiology ; *Nervous System Diseases/therapy/pathology/metabolism ; Animals ; *Cell Polarity/physiology ; Microglia/metabolism/pathology ; }, abstract = {Glial cell polarization plays a pivotal role in various neurological disorders. In response to distinct stimuli, glial cells undergo polarization to either mitigate neurotoxicity or facilitate neural repair following injury, underscoring the importance of glial phenotypic polarization in modulating central nervous system function. This review presents an overview of glial cell polarization, focusing on astrocytes and microglia. It explores the involvement of glial polarization in neurological diseases such as Alzheimer's disease, Parkinson's disease, stroke, epilepsy, traumatic brain injury, amyotrophic lateral sclerosis, multiple sclerosis and meningoencephalitis. Specifically, it emphasizes the role of glial cell polarization in disease pathogenesis through mechanisms including neuroinflammation, neurodegeneration, calcium signaling dysregulation, synaptic dysfunction and immune response. Additionally, it summarizes various therapeutic strategies including pharmacological treatments, dietary supplements and cell-based therapies, aimed at modulating glial cell polarization to ameliorate brain dysfunction. Future research focused on the spatio-temporal manipulation of glial polarization holds promise for advancing precision diagnosis and treatment of neurological diseases.}, } @article {pmid39671529, year = {2024}, author = {Katzman, D and Kalman, G and Almog, O and Fogel, I}, title = {Deployment of Physician Resources and Innovative Medical Strategies in the 2023-2024 Israel-Hamas War: Israel's Strategy to Deliver Advanced Life Support and Whole Blood Transfusion to the Battlefield via Forward Medical Teams and the Impact on the Case Fatality Rate.}, journal = {Military medicine}, volume = {}, number = {}, pages = {}, doi = {10.1093/milmed/usae553}, pmid = {39671529}, issn = {1930-613X}, abstract = {The 2023-2024 Israel-Hamas War, which began following a Hamas attack on Israel on October 7, 2023, has seen a case fatality rate (CFR) among the lowest in the history of warfare. In resultant ground maneuvers, the Israel Defense Forces Medical Corps (IDF-MC) doctrine for the delivery of combat casualty care has been battle tested. We suggest the decreased CFR in part reflects a paradigm shift in combat deployment of medical resources, so as to introduce life-saving strategies not previously seen on the battlefield in large scale to date. These changes, which began in the 2006 Lebanon war and have been in evolution since, include strategic physician deployment to positions more forward than in previous wars and in teams smaller than the previous standard. These forward medical teams have replaced the battalion aid station in the Gaza theater of operations and serve to increase the availability of Advanced Life Support (ALS) level care at the point of injury, wherever a casualty might be on a multidimensional battlefield. These forward medical teams deploy with advanced medical capabilities, including in some cases the ability to transfuse low titer O whole blood. This article reviews aspects of the IDF-MC combat casualty care doctrine as implemented during the current war, the role and advantages of transfusion-capable ALS forward medical teams, and the apparent impact on the CFR thereof.}, } @article {pmid39671291, year = {2024}, author = {Lin, J and Carman, PJ and Gambogi, CW and Kendsersky, NM and Chuang, E and Gates, SN and Yokom, AL and Rizo, AN and Southworth, DR and Shorter, J}, title = {Design principles to tailor Hsp104 therapeutics.}, journal = {Cell reports}, volume = {43}, number = {12}, pages = {115005}, pmid = {39671291}, issn = {2211-1247}, support = {R01 GM099836/GM/NIGMS NIH HHS/United States ; R01 GM110001/GM/NIGMS NIH HHS/United States ; T32 GM008076/GM/NIGMS NIH HHS/United States ; }, mesh = {Humans ; *Heat-Shock Proteins/metabolism ; HSP70 Heat-Shock Proteins/metabolism ; Adenosine Triphosphate/metabolism ; Saccharomyces cerevisiae Proteins/metabolism/genetics ; HSP40 Heat-Shock Proteins/metabolism/genetics ; HEK293 Cells ; Adenosine Diphosphate/metabolism ; Protein Binding ; }, abstract = {The hexameric AAA+ disaggregase, Hsp104, collaborates with Hsp70 and Hsp40 via its autoregulatory middle domain (MD) to solubilize aggregated proteins. However, how ATP- or ADP-specific MD configurations regulate Hsp104 hexamers remains poorly understood. Here, we define an ATP-specific network of interprotomer contacts between nucleotide-binding domain 1 (NBD1) and MD helix L1, which tunes Hsp70 collaboration. Manipulating this network can (1) reduce Hsp70 collaboration without enhancing activity, (2) generate Hsp104 hypomorphs that collaborate selectively with class B Hsp40s, (3) produce Hsp70-independent potentiated variants, or (4) create species barriers between Hsp104 and Hsp70. Conversely, ADP-specific intraprotomer contacts between MD helix L2 and NBD1 restrict activity, and their perturbation frequently potentiates Hsp104. Importantly, adjusting an NBD1:MD helix L1 rheostat via rational design enables finely tuned collaboration with Hsp70 to safely potentiate Hsp104, minimize off-target toxicity, and counteract FUS and TDP-43 proteinopathies in human cells. Thus, we establish design principles to tailor Hsp104 therapeutics.}, } @article {pmid39671140, year = {2025}, author = {Ikehata, A}, title = {Extension of the molar absorption coefficient for non-ideal mixtures: an application to aqueous monovalent alcohol solutions.}, journal = {Analytical sciences : the international journal of the Japan Society for Analytical Chemistry}, volume = {41}, number = {4}, pages = {353-363}, pmid = {39671140}, issn = {1348-2246}, abstract = {The hydration state of the alcohols was investigated using the extended molar absorption coefficient, which redefines the molar absorption coefficient as a differential coefficient of concentration. The extended molar absorption coefficient is a function of the concentration calculated from the difference in absorbance, and is consistent with the conventional molar absorption coefficient, allowing a complete quantitative comparison. The quantitative performance was verified using IR and NIR absorption spectra of aqueous solutions of monovalent alcohols (methanol, ethanol, 1-propanol, 2-propanol, and tert-butanol) that were soluble in water at any mixing ratio. Extended molar absorption coefficient spectra were calculated for the combination bands of water, which were further separated by multivariate curve resolution-alternating least squares (MCR-ALS) into molecular species with different peak wavenumbers: strongly hydrogen-bonded (SHB), weakly hydrogen-bonded (WHB), and free OH species. The number of water species that change when one alcohol molecule increases, i.e., the perturbed hydration number (PHN), was calculated by comparison with the conventional molar absorption coefficient of pure water. The calculated PHN indicates that the numbers of SHB and WHB species are reversed at approximately 20 wt%, and that the free OH species increase at higher alcohol concentrations and are more pronounced for alcohols with bulky alkyl groups. These results provide a quantitative answer to the long-debated question of anomalies in water-alcohol mixing.}, } @article {pmid39670820, year = {2025}, author = {Lagiakos, HR and Zou, Y and Igawa, H and Therrien, E and Lawrenz, M and Kato, M and Svensson, M and Gray, F and Jensen, K and Dahlgren, MK and Pelletier, RD and Dingley, K and Bell, JA and Liu, Z and Jiang, Y and Zhou, H and Skene, RJ and Nie, Z}, title = {In Silico Enabled Discovery of KAI-11101, a Preclinical DLK Inhibitor for the Treatment of Neurodegenerative Disease and Neuronal Injury.}, journal = {Journal of medicinal chemistry}, volume = {68}, number = {3}, pages = {2720-2741}, doi = {10.1021/acs.jmedchem.4c02074}, pmid = {39670820}, issn = {1520-4804}, mesh = {Animals ; *Neurodegenerative Diseases/drug therapy ; Humans ; Mice ; *Neuroprotective Agents/pharmacology/chemistry/therapeutic use/chemical synthesis ; *Protein Kinase Inhibitors/pharmacology/chemistry/therapeutic use/chemical synthesis ; MAP Kinase Kinase Kinases/antagonists & inhibitors/metabolism ; Neurons/drug effects/pathology/metabolism ; Drug Discovery ; Computer Simulation ; Structure-Activity Relationship ; Rats ; }, abstract = {Dual leucine zipper kinase (DLK), expressed primarily in neuronal cells, is a regulator of neuronal degeneration in response to cellular stress from chronic disease or neuronal injury. This makes it an attractive target for the treatment of neurodegenerative diseases such as Alzheimer's, Parkinson's, and amyotrophic lateral sclerosis, and neuronal injury, such as chemotherapy-induced peripheral neuropathy. Here, we describe the discovery of a potent, selective, brain-penetrant DLK inhibitor, KAI-11101 (59). Throughout the program's progression, medicinal chemistry challenges such as potency, hERG inhibition, CNS penetration, CYP3A time-dependent inhibition, and kinase selectivity were overcome through the implementation of cutting-edge in silico tools. KAI-11101 displayed an excellent in vitro safety profile and showed neuroprotective properties in an ex vivo axon fragmentation assay as well as dose-dependent activity in a mouse PD model.}, } @article {pmid39670434, year = {2025}, author = {Piga, G and Fadda, L and Borghero, G and Maccabeo, A and Pala, F and Murru, MR and Giglio, S and Puligheddu, M and Floris, G}, title = {Semantic behavioral variant frontotemporal dementia and semantic dementia associated with TARDBP mutations.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {26}, number = {3-4}, pages = {358-367}, doi = {10.1080/21678421.2024.2439448}, pmid = {39670434}, issn = {2167-9223}, mesh = {Humans ; *Frontotemporal Dementia/genetics/diagnosis ; Male ; Female ; Middle Aged ; Aged ; *DNA-Binding Proteins/genetics ; *Mutation/genetics ; Cohort Studies ; Semantics ; }, abstract = {Frontotemporal dementia (FTD) is a highly heritable group of neurodegenerative disorders, characterized by varying clinical and pathological features. TARDBP gene has been described worldwide within the FTD/ALS spectrum but its association with right and left temporal variant of FTD (tvFTD) is still unclear. This study aimed to reclassify a Sardinian FTD cohort according to proposed criteria for the semantic behavioral variant FTD (sbvFTD), explore TARDBP mutations' association with tvFTD, and review related literature. From our FTD cohort of 94 patients, ten fulfilled the criteria for sbvFTD. Therefore, in light of the diagnostic reclassification carried out, we describe the largest series of unrelated patients with TARDBP p.A382T missense mutation, including four new cases of tvFTD: two sbvFTD and two svPPA, exhibiting semantic and behavioral disorders and showing predominant right and left anterior temporal lobe involvement, respectively. We present for the first time two sbvFTD cases carrying the pA382T TARDBP mutation. Comparison with C9orf72 and non-mutated patients revealed lower age at onset (p = 0.006), and a higher prevalence of tvFTD, particularly sbvFTD (p < 0.001), and motor neuron disease in TARDBP carriers (p < 0.001). Our findings along with a review of the literature highlighted TARDBP mutations' association with sbvFTD and semantic dementia, suggesting a genetic role in temporal variants of FTD and emphasizing the need for TARDBP mutation screening in these cases. Reclassifying FTD cohorts, including the sbvFTD phenotype, could aid in better defining the clinical spectrum of tvFTD and guide differential diagnosis across different FTD populations with TARDBP or other FTD-related mutations.}, } @article {pmid39670345, year = {2025}, author = {D'Anna, L and Wragg, D and Mauro, D and Rubino, S and Terenzi, A and Barone, G and Thomas, SR and Casini, A and Bonsignore, R and Spinello, A}, title = {Unraveling the Molecular Basis for G-Quadruplex-Binders to ALS/FTD-Associated G4C2 Repeats of the C9orf72 Gene.}, journal = {Chembiochem : a European journal of chemical biology}, volume = {26}, number = {8}, pages = {e202400974}, pmid = {39670345}, issn = {1439-7633}, support = {PNRR-M4C2-I1.3//European Union-NextGenerationEU/ ; PE_00000019//European Union-NextGenerationEU/ ; B73C22001250006//European Union-NextGenerationEU/ ; }, mesh = {*G-Quadruplexes/drug effects ; *C9orf72 Protein/genetics/chemistry ; *Amyotrophic Lateral Sclerosis/genetics ; Humans ; *Frontotemporal Dementia/genetics ; Fluorescence Resonance Energy Transfer ; }, abstract = {The most recurrent familial cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) is the presence of an abnormal number of intronic GGGGCC (G4C2) repetitions in the C9orf72 gene, which has been proposed to drive ALS/FTD pathogenesis. Recently, it has been shown that such G4C2 repetitions can fold into G-quadruplex (G4) secondary structures. These G4s have been selectively stabilized by small-molecule binders, furnishing proof-of-principle that targeting these non-canonical nucleic acid sequences represents a novel and effective therapeutic strategy to tackle neurodegenerative disorders. However, precise information on the mechanism of action of these compounds is still lacking. Here, by performing in silico investigations, we unraveled the molecular basis for the selectivity of a series of known structurally related C9orf72 G4-binders. Moreover, we investigated the binding properties of a strong and selective metal-based G4 stabilizer, the Au[I] bis-N-heterocyclic carbene (NHC) complex - Au(TMX)2 - showing that it moderately stabilizes G4C2 G4 RNA by Förster resonance energy transfer (FRET) DNA melting assays. Using metadynamics (metaD) simulations, the Au(TMX)2 binding mode and the associated free-energy landscape were also evaluated. This information paves the way for developing improved compounds to tackle ALS/FTD neurodegenerative disorders.}, } @article {pmid39670112, year = {2024}, author = {Pinkerton, M and Adler, GL and Ledger, M and Ni, CY and Yang, Y and Tan, RH}, title = {Heterogeneous nuclear ribonucleoprotein D - an understudied subfamily affected in sporadic TDP-43 proteinopathies.}, journal = {Brain communications}, volume = {6}, number = {6}, pages = {fcae352}, pmid = {39670112}, issn = {2632-1297}, abstract = {Despite the recognition that heterogeneous nuclear ribonucleoproteins (hnRNPs) modulate TDP-43 and can limit aberrant splicing events to compensate for TDP-43 loss, their role in TDP-43 proteinopathies remains poorly understood and studies in patient tissue are lacking. This study assesses seven heterogeneous nuclear ribonucleoproteins from the A/B, C, D and H subfamilies in two cortical regions implicated in early TDP-43 dysfunction versus late TDP-43 dysfunction in sporadic amyotrophic lateral sclerosis and/or frontotemporal lobar degeneration. Our results reveal significant nuclear loss of hnRNPD, hnRNPC and hnRNPA1 in the frontal cortex of frontotemporal lobar degeneration compared to amyotrophic lateral sclerosis but not in the motor cortical neurons or Betz cells of amyotrophic lateral sclerosis cases. Cytoplasmic co-occurrence was observed between hnRNPA1 and hnRNPC but not with phosphorylated TDP-43 (pTDP-43). Interestingly, nuclear hnRNPD loss associated with increasing cytoplasmic pTDP-43, highlighting an understudied subfamily in sporadic TDP-43 proteinopathies. In summary, this study identifies the nuclear loss of hnRNPD, C and A1 in a predilection brain region of TDP-43 in frontotemporal lobar degeneration compared to amyotrophic lateral sclerosis cases without significant pTDP-43 in this region. This highlights the need for further investigation into the involvement of these heterogeneous nuclear ribonucleoproteins in disease pathogenesis and potential to serve as modulatory targets and/or proximal markers of TDP-43 dysfunction in sporadic TDP-43 proteinopathies.}, } @article {pmid39669591, year = {2024}, author = {Beauregard-Lacroix, É and Scott, A and Nguyen, TTM and Wierenga, KJ and Purcarin, G and Karstensen, AB and Carvalho, DR and Alessandri, JL and Payet, F and Girisha, KM and Ferron, M and Campeau, PM}, title = {Exploring the phenotypic spectrum and osteopenia mechanisms in Yunis-Varón syndrome.}, journal = {Genetics in medicine open}, volume = {2}, number = {}, pages = {101837}, pmid = {39669591}, issn = {2949-7744}, abstract = {PURPOSE: Biallelic variants in FIG4 or VAC14 are associated with Yunis-Varón syndrome (YVS), which is characterized by multisystem involvement including skeletal findings, craniofacial dysmorphisms and central nervous system anomalies. Pathogenic variants in those same genes have also been associated with a predominantly neurological phenotype and with nonsyndromic conditions, such as Charcot-Marie-Tooth disease and amyotrophic lateral sclerosis. By describing 5 new cases of FIG4-associated YVS and reviewing the literature, we better delineate the clinical phenotype associated with loss of function of those genes. We also explore osteopenia mechanisms by assessing bone physiologic parameters in a mouse model.

METHODS: Exome sequencing or Sanger sequencing was performed in 5 unrelated individuals. Bone histomorphometry was performed in Fig4 [plt/plt] mice and compared with wild type. Relevant literature from the last 10 years was reviewed.

RESULTS: All individuals presented a phenotype overlapping the typical YVS and the brain anomalies and neurologic syndrome. Clinical features included developmental delay, structural brain malformations, and skeletal anomalies, such as osteopenia. Biallelic FIG4 variants were identified in each individual. In mice, bone histomorphometry parameters suggested that osteopenia might be secondary to reduced bone formation rather than increased bone degradation.

CONCLUSION: This study contributes to a better understanding of the phenotypic variability caused by pathogenic variants in FIG4 or VAC14 and suggests an important overlap between previously described phenotypes. The brain anomalies and neurologic syndrome is likely in the same spectrum as classical YVS. Further studies are still needed to clarify the effects of partial loss-of-function (hypomorphic) variants and to identify genotype-phenotype correlations.}, } @article {pmid39669124, year = {2024}, author = {Mirceta, M and Schmidt, MHM and Shum, N and Prasolava, TK and Meikle, B and Lanni, S and Mohiuddin, M and McKeever, PM and Zhang, M and Liang, M and van der Werf, I and Scheers, S and Dion, PA and Wang, P and Wilson, MD and Abell, T and Philips, EA and Sznajder, ŁJ and Swanson, MS and Mehkary, M and Khan, M and Yokoi, K and Jung, C and de Jong, PJ and Freudenreich, CH and McGoldrick, P and Yuen, RKC and Abrahão, A and Keith, J and Zinman, L and Robertson, J and Rogaeva, E and Rouleau, GA and Kooy, RF and Pearson, CE}, title = {C9orf72 repeat expansion creates the unstable folate-sensitive fragile site FRA9A.}, journal = {NAR molecular medicine}, volume = {1}, number = {4}, pages = {ugae019}, pmid = {39669124}, issn = {2976-856X}, support = {P50 NS048843/NS/NINDS NIH HHS/United States ; R01 GM122880/GM/NIGMS NIH HHS/United States ; R35 GM144215/GM/NIGMS NIH HHS/United States ; U54 NS048843/NS/NINDS NIH HHS/United States ; }, abstract = {The hyper-unstable Chr9p21 locus, harbouring the interferon gene cluster, oncogenes and C9orf72, is linked to multiple diseases. C9orf72 (GGGGCC)n expansions (C9orf72Exp) are associated with incompletely penetrant amyotrophic lateral sclerosis, frontotemporal dementia and autoimmune disorders. C9orf72Exp patients display hyperactive cGAS-STING-linked interferon immune and DNA damage responses, but the source of immunostimulatory or damaged DNA is unknown. Here, we show C9orf72Exp in pre-symptomatic and amyotrophic lateral sclerosis-frontotemporal dementia patient cells and brains cause the folate-sensitive chromosomal fragile site, FRA9A. FRA9A centers on >33 kb of C9orf72 as highly compacted chromatin embedded in an 8.2 Mb fragility zone spanning 9p21, encompassing 46 genes, making FRA9A one of the largest fragile sites. C9orf72Exp cells show chromosomal instability, heightened global- and Chr9p-enriched sister-chromatid exchanges, truncated-Chr9s, acentric-Chr9s and Chr9-containing micronuclei, providing endogenous sources of damaged and immunostimulatory DNA. Cells from one C9orf72Exp patient contained a highly rearranged FRA9A-expressing Chr9 with Chr9-wide dysregulated gene expression. Somatic C9orf72Exp repeat instability and chromosomal fragility are sensitive to folate deficiency. Age-dependent repeat instability, chromosomal fragility and chromosomal instability can be transferred to CNS and peripheral tissues of transgenic C9orf72Exp mice, implicating C9orf72Exp as the source. Our results highlight unappreciated effects of C9orf72 expansions that trigger vitamin-sensitive chromosome fragility, adding structural variations to the disease-enriched 9p21 locus, and likely elsewhere.}, } @article {pmid39667814, year = {2025}, author = {Rousseau, JA and Maier, M and Ait-Mohand, S and Dumulon-Perreault, V and Sarrhini, O and Tremblay, S and Rousseau, E and Salzmann, M and Guérin, B}, title = {Antibody-Based PET Imaging of Misfolded Superoxide Dismutase 1 in an Amyotrophic Lateral Sclerosis Mouse Model.}, journal = {Journal of nuclear medicine : official publication, Society of Nuclear Medicine}, volume = {66}, number = {1}, pages = {130-135}, pmid = {39667814}, issn = {1535-5667}, mesh = {Animals ; *Amyotrophic Lateral Sclerosis/diagnostic imaging ; Mice ; *Superoxide Dismutase-1/metabolism/genetics ; *Positron-Emission Tomography/methods ; *Disease Models, Animal ; *Zirconium/chemistry ; Protein Folding ; Mice, Transgenic ; Deferoxamine/chemistry ; Antibodies/chemistry ; Radioisotopes ; Tissue Distribution ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a rare neurodegenerative disease characterized by motor neuron loss in the motor cortex, brain stem, and spinal cord. Mutations in the superoxide dismutase 1 (SOD1) gene, resulting in misfolding of its protein product, are a common cause of ALS. Currently, there is no approved ALS diagnostic tool. Here, we present the development of a PET radiotracer, [[89]Zr]Zr-desferoxamine (DFO)-α-miSOD1, targeting selectively misfolded SOD1 (misSOD1). Methods: DFO-α-miSOD1 was prepared by conjugating α-miSOD1 antibody with DFO and labeled with [89]Zr. A longitudinal imaging study was performed to identify the optimal mouse age and time after administration of [[89]Zr]Zr-DFO-α-miSOD1 for the detection of misSOD1 aggregation in transgenic mice overexpressing misSOD1 and in wild-type mice. Subsets of mice were either coinjected with an excess of α-miSOD1 or imaged with deglycosylated [[89]Zr]Zr-DFO-α-miSOD1 to assess target specificity. The internal radiation dose for [[89]Zr]Zr-DFO-α-miSOD1 was estimated by extrapolating data from mouse biodistribution experiments. Results: Imaging with [[89]Zr]Zr-DFO-α-miSOD1 was optimal in 136-d-old transgenic mice on day 10 after administration. Significant accumulation of [[89]Zr]Zr-DFO-α-miSOD1 was detected in the spinal cord and cartilage of ALS transgenic mice compared with the wild-type mice (P = 0.01). The radiotracer accumulation is selective and blockable with an excess of α-miSOD1. Deglycosylated [[89]Zr]Zr-DFO-α-miSOD1 results in high-contrast detection of misSOD1 but is prone to aggregation. The dosimetry for [[89]Zr]Zr-DFO-α-miSOD1 is comparable to that for other [89]Zr-based tracers currently used in humans. Conclusion: This work thus establishes that [[89]Zr]Zr-DFO-α-miSOD1 PET can detect misSOD1 in transgenic mice, paving the way for application in early diagnosis of ALS and therapeutic monitoring.}, } @article {pmid39667295, year = {2025}, author = {Spencer, PS and Berntsson, SG and Buguet, A and Butterfield, P and Calne, DB and Calne, SM and Giménez-Roldán, S and Hugon, J and Kahlon, S and Kisby, GE and Lagrange, E and Landtblom, AE and Ludolph, AC and Nunn, PB and Palmer, VS and Reis, J and Román, GC and Sipilä, JOT and Spencer, SS and Angues, RV and Vernoux, JP and Yabushita, M}, title = {Brain health: Pathway to primary prevention of neurodegenerative disorders of environmental origin.}, journal = {Journal of the neurological sciences}, volume = {468}, number = {}, pages = {123340}, doi = {10.1016/j.jns.2024.123340}, pmid = {39667295}, issn = {1878-5883}, mesh = {Humans ; *Neurodegenerative Diseases/prevention & control/etiology/epidemiology ; *Primary Prevention/methods ; *Brain ; *Environmental Exposure/adverse effects ; }, abstract = {While rising global rates of neurodegenerative disease encourage early diagnosis and therapeutic intervention to block clinical expression (secondary prevention), a more powerful approach is to identify and remove environmental factors that trigger long-latencybrain disease (primary prevention) by acting on a susceptible genotype or acting alone. The latter is illustrated by the post-World War II decline and disappearance of Amyotrophic Lateral Sclerosis and Parkinsonism-Dementia Complex (ALS/PDC), a prototypical often-familial neurodegenerative disease formerly present in very high incidence on the island of Guam. Lessons learned from 75 years of investigation on the etiology of ALS/PDC include: the importance of focusing field research on the disease epicenter and patients with early-onset disease; soliciting exposure history from patients, family, and community to guide multidisciplinary biomedical investigation; recognition that disease phenotype may vary with exposure history, and that familial brain disease may have a primarily environmental origin. Furthermore, removal from exposure to the environmental trigger effects primary disease prevention.}, } @article {pmid39666202, year = {2024}, author = {van Eijk, RPA and van Loon, FT and van Unnik, JWJ and Weemering, DN and Seitidis, G and Mavridis, D and van den Berg, LH and Nikolakopoulos, S}, title = {Attrition and discontinuation in amyotrophic lateral sclerosis clinical trials: a meta-analysis.}, journal = {Journal of neurology}, volume = {272}, number = {1}, pages = {40}, pmid = {39666202}, issn = {1432-1459}, support = {EVIDENCE//Stichting ALS Nederland/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/therapy ; Humans ; *Randomized Controlled Trials as Topic ; Patient Dropouts/statistics & numerical data ; }, abstract = {OBJECTIVES: Attrition due to adverse events and disease progression impacts the integrity and generalizability of clinical trials. The aim of this study is to provide evidence-based estimates of attrition for clinical trials in amyotrophic lateral sclerosis (ALS), and identify study-related predictors, through a comprehensive systematic review and meta-analysis.

METHODS: We systematically reviewed the literature to identify all randomized, placebo-controlled clinical trials in ALS and determined the number of patients who discontinued the study per randomized arm. Subsequently, we meta-analyzed attrition rates across studies, evaluated the difference between study arms, and explored the impact of study-level characteristics. Finally, a meta-regression model predicting study discontinuation for future clinical trials was translated into a web application.

RESULTS: In total, 60 randomized placebo-controlled clinical trials were included in the meta-analysis, randomizing 14,493 patients with ALS. Attrition varied significantly between studies, ranging from 3.1% to 75.7% of all randomized patients, with a pooled effect of 32.0% (90% prediction interval 6.1% to 66.3%). Attrition was similar between the intervention and placebo arm (odds ratio 1.08, 95% CI 0.89 to 1.31, p = 0.43). The follow-up duration was identified as the sole study-level predictor (0.032, 95% CI 0.026 to 0.039, p < 0.001), resulting in predicted attrition of 19.3% for 6-month, 36.4% for 12-month, and 55.6% for 18-month clinical trials.

CONCLUSIONS: ALS clinical trials encounter high attrition, which increases with the follow-up duration. These findings underscore the need to refine our strategies to manage attrition, preserving the integrity and generalizability of ALS clinical trials.}, } @article {pmid39666144, year = {2024}, author = {Levison, LS and Blicher, JU and Andersen, H}, title = {Incidence and mortality of ALS: a 42-year population-based nationwide study.}, journal = {Journal of neurology}, volume = {272}, number = {1}, pages = {44}, pmid = {39666144}, issn = {1432-1459}, support = {A3520//Health Research Fund of Central Denmark Region/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/epidemiology/mortality ; Male ; Female ; Incidence ; Middle Aged ; Denmark/epidemiology ; Aged ; Adult ; Aged, 80 and over ; Young Adult ; Adolescent ; }, abstract = {BACKGROUND AND AIM: Recent studies have suggested that the incidence rate (IR) and the rate of death (MR) of amyotrophic lateral sclerosis (ALS) are increasing. Still, it remains unclear whether this is due to improved case ascertainment or represents a true increase. We examined the development in the incidence and mortality of ALS in Denmark for 42 years.

METHODS: We retrieved individual-level data of all patients aged above 18 years with first-time ALS diagnosed at any Danish department of neurology. The IR and MR were calculated based on data from 1980 to 2021, stratified by gender and age.

RESULTS: We identified 5,943 patients with ALS and identified a total of 5,069 deaths in the nationwide population. Overall, the IR was 3.4 per 100,000 persons per year (95% CI 3.4-3.5). ALS incidence rose gradually during the study period, and the IR was 2.8 times higher (95% CI 2.4-3.2) when comparing the latest period (2018-2021) with the first (1980-1983). Parallel to the IR, the MR increased over time and was associated with male gender and rose with age at diagnosis, peaking in the 70-79-year age group.

CONCLUSION: In Denmark, the IR and MR of ALS increased threefold from 1980 to 2021, with steadily increasing risk related to male gender and in particular to higher age. Considering our aging societies, the number of elderly patients with ALS can be expected to increase considerably.}, } @article {pmid39666121, year = {2024}, author = {Okubo, S and Naruse, H and Ishiura, H and Sudo, A and Esaki, K and Mitsui, J and Matsukawa, T and Satake, W and Greimel, P and Shingai, N and Oya, Y and Yoshikawa, T and Tsuji, S and Toda, T}, title = {Genetic and functional analyses of SPTLC1 in juvenile amyotrophic lateral sclerosis.}, journal = {Journal of neurology}, volume = {272}, number = {1}, pages = {36}, pmid = {39666121}, issn = {1432-1459}, support = {JPMH23FC1008//Ministry of Health, Labour and Welfare/ ; JP23ek0109673//Japan Agency for Medical Research and Development/ ; JP23ek0109617//Japan Agency for Medical Research and Development/ ; JP23ek0109631//Japan Agency for Medical Research and Development/ ; JP24K18698//Japan Society for the Promotion of Science/ ; JP23K27514//Japan Society for the Promotion of Science/ ; 21K07512//Japan Society for the Promotion of Science/ ; Glyco-lipidologue Initiative Program//RIKEN/ ; }, mesh = {Adolescent ; Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Young Adult ; *Amyotrophic Lateral Sclerosis/genetics/diagnosis/blood ; Mutation ; Pedigree ; *Serine C-Palmitoyltransferase/genetics ; Sphingolipids/blood ; }, abstract = {INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder of the motor system. Pathogenic variants in SPTLC1, encoding a subunit of serine palmitoyltransferase, cause hereditary sensory and autonomic neuropathy type 1 (HSAN1), and have recently been associated with juvenile ALS. SPTLC1 variants associated with ALS cause elevated levels of sphinganines and ceramides. Reports on ALS associated with SPTLC1 remain limited. This study aimed to investigate the frequency of SPTLC1 variants in ALS and relevant clinical characteristics.

METHODS: We analyzed whole-exome and whole-genome sequence data from 40 probands with familial ALS and 413 patients with sporadic ALS without previously identified causative variants. Reverse transcription polymerase chain reaction (RT-PCR) analysis and droplet digital PCR (ddPCR) were used to assess splicing and mosaicism, respectively. Plasma sphingolipid levels were quantified to analyze biochemical consequences.

RESULTS: The heterozygous c.58G>A, p.Ala20Thr variant was identified in a 21-year-old Japanese female patient presenting with symmetric weakness which slowly progressed over 15 years. RT-PCR analysis showed no splice defects. Plasma sphingolipid levels in the patient were significantly increased compared to her asymptomatic parents. ddPCR revealed that the asymptomatic father harbored a mosaic variant with 17% relative mutant allele abundance in peripheral blood leukocytes.

CONCLUSIONS: We identified a pathogenic c.58G>A, p.Ala20Thr SPTLC1 variant in a patient with juvenile ALS, likely inherited from an asymptomatic parent with mosaicism. Lipid analysis results are consistent with previous findings on SPTLC1-associated ALS. Further studies are necessary to determine the clinical effect of mosaic variants of SPTLC1.}, } @article {pmid39666115, year = {2024}, author = {Psychogios, I and Hu, Y and Seitz, C and Joyce, EE and Lovik, A and Ingre, C and Fang, F}, title = {Exploring clinical chemistry markers in amyotrophic lateral sclerosis: insights into survival and disease trajectories.}, journal = {Journal of neurology}, volume = {272}, number = {1}, pages = {7}, pmid = {39666115}, issn = {1432-1459}, support = {2019-01088//Swedish Research Council/ ; 2023-02428//Swedish Research Council/ ; MegaALS 802091//European Research Council Starting Grant/ ; R01 TS000324/TS/ATSDR CDC HHS/United States ; R01TS000324-01-00/CC/CDC HHS/United States ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/blood/mortality/diagnosis/physiopathology ; Male ; Female ; Middle Aged ; *Biomarkers/blood ; Aged ; *Disease Progression ; Cohort Studies ; Sweden ; Adult ; Prognosis ; }, abstract = {OBJECTIVE: Commonly measured clinical chemistry markers might be indicative of survival and disease progression in amyotrophic lateral sclerosis (ALS).

METHODS: In a cohort study of 270 ALS patients diagnosed from April 2014 to May 2021 in Stockholm, Sweden, we examined the link between 29 clinical chemistry markers at diagnosis and mortality risk at 6 months, 1 year, and 3 years after diagnosis. Summary variables from exploratory factor analysis (EFA) assessed the markers' collective impact on survival. We integrated ALS functional rating scale-revised (ALSFRS-R) scores with survival data using a joint latent class model to identify patterns of functional decline. Multinomial logistic regression determined how the EFA-derived factors predicted the decline trajectories post-diagnosis.

RESULTS: Higher levels of total cholesterol, low-density lipoprotein cholesterol (LDL-C), apolipoprotein B, and albumin at diagnosis were linked to lower mortality in ALS patients, while increased neurofilament light chain (NfL), leukocyte count, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and carbon dioxide (CO2) levels indicated higher mortality. The 'Red blood cell profile' factor, derived from EFA, emerged as a significant predictor of survival, independent of other prognostic indicators. The joint latent class model identified three distinct patient groups based on functional decline, with 'Red blood cell profile' suggesting a lower likelihood of being in the groups with slower progression.

CONCLUSION: Clinical chemistry markers, including NfL, lipids, albumin, leukocyte count, MCV, MCH, CO2, and the 'Red blood cell profile,' were associated with ALS survival. As these markers represent broader bodily functions, integrating them in ALS patient care could improve disease management.}, } @article {pmid39666103, year = {2024}, author = {Zimmermann, M and Mengel, D and Raupach, K and Haack, T and Neumann, M and Synofzik, M}, title = {Frequency and neuropathology of HTT repeat expansions in FTD/ALS: co-existence rather than causation.}, journal = {Journal of neurology}, volume = {272}, number = {1}, pages = {58}, pmid = {39666103}, issn = {1432-1459}, mesh = {Humans ; *Frontotemporal Dementia/genetics/pathology ; *Amyotrophic Lateral Sclerosis/genetics/pathology ; Male ; Female ; *Huntingtin Protein/genetics ; Middle Aged ; Aged ; *Trinucleotide Repeat Expansion/genetics ; Brain/pathology/diagnostic imaging ; }, abstract = {INTRODUCTION: While ≥ 40 CAG repeat expansions in HTT present a well-established cause of Huntington's disease (HD), an enrichment of HTT repeat expansions was recently reported also in patients with amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), including FTD/ALS patients with additional HD neuropathology. This raises the question whether the phenotypic spectrum of HTT expansions can be extended to ALS and FTD, and whether HTT should be considered as a new causative gene of FTD/ALS. If HTT repeat expansions were indeed systematically related to FTD/ALS, one would expect an increased frequency of HTT carriers in FTD/ALS, who can clinically/neuropathologically not be explained better than by the presence of the HTT repeat expansions.

METHODS: Screening of HTT repeat expansions in 249 consecutive patients with ALS or FTD by short-read genome sequencing took place. The post-mortem neuropathological examination was performed in the identified HTT repeat expansion carrier.

RESULTS: One HTT repeat expansion [40/22 repeats (± 1)] was identified in an ALS patient, giving a frequency of 0.4% (1/249) (frequency in the general population: 0.03-0.18%). This patient showed a classic ALS phenotype, but no clinical or imaging signs of HD. Post-mortem brain examination revealed-in addition to ALS-typical degeneration of upper and lower motor neurons with TDP-43 inclusions-HD-typical polyQ-aggregates in gyrus cinguli, striatum and frontal lobe, yet without evidence of striatal degeneration.

CONCLUSIONS: Our study does not support the notion of an increased frequency of HTT repeat expansions in FTD/ALS. Moreover, the phenotype of the HTT carrier identified can be better explained by two co-existent, but independent diseases: (i) ALS and (ii) presymptomatic HD, which-given the low repeat number-is likely to become manifest only later in life. These findings corroborate the concept that HTT repeat expansions are likely co-existent/coincidental, but not causative in FTD/ALS.}, } @article {pmid39666071, year = {2024}, author = {de Boer, EMJ and de Vries, BS and Van Hecke, W and Mühlebner, A and Vincken, KL and Mol, CP and van Rheenen, W and Westeneng, HJ and Veldink, JH and Höglinger, GU and Morris, HR and Litvan, I and Raaphorst, J and Ticozzi, N and Corcia, P and Vandenberghe, W and Pijnenburg, YAL and Seelaar, H and Ingre, C and Van Damme, P and van den Berg, LH and van de Warrenburg, BPC and van Es, MA}, title = {Diagnosing primary lateral sclerosis: a clinico-pathological study.}, journal = {Journal of neurology}, volume = {272}, number = {1}, pages = {46}, pmid = {39666071}, issn = {1432-1459}, mesh = {Humans ; Amyotrophic Lateral Sclerosis/diagnosis/pathology/genetics ; Autopsy ; Brain/pathology/diagnostic imaging ; Diagnosis, Differential ; *Motor Neuron Disease/diagnosis/pathology ; }, abstract = {BACKGROUND: Primary lateral sclerosis (PLS) is a rare motor neuron disease characterized by upper motor neuron degeneration, diagnosed clinically due to the absence of a (neuropathological) gold standard. Post-mortem studies, particularly TDP-43 pathology analysis, are limited.

METHODS: This study reports on 5 cases in which the diagnostic criteria for PLS were met, but in which neuropathology findings showed (partially) conflicting results. These discrepancies prompted us to perform a clinico-pathology study focussing on diagnostic challenges and accuracy in PLS. To this end, all cases were reviewed by an international panel of 11 experts using an e-module and structured questionnaires.

RESULTS: Autopsy exhibited neuropathological findings consistent with amyotrophic lateral sclerosis (ALS) in one case, while two cases exhibited similar, but more limited lower motor neuron involvement, hinting at PLS or ALS overlap. Another case displayed tau-pathology indicative of progressive supranuclear palsy. The final case displayed extensive myelin loss without a proteinopathy or a clear diagnosis. The expert panel identified 24 different ancillary investigations lacking across cases (e.g. genetic testing, DAT scans, neuropsychological evaluation), listed 28 differential diagnoses, and identified 13 different conditions as the most likely diagnosis. Autopsy results led panel members to change their final diagnosis in 42% of the cases.

CONCLUSIONS: This study underscores the diagnostic challenges posed by diverse underlying pathologies resulting in upper motor neuron phenotypes. Despite adhering to the same diagnostic criteria, consensus amongst experts was limited. Ensuring the diagnostic consistency is crucial for advancing understanding and treatment of PLS. Explicit guidelines for excluding potential mimics along with a neuropathological gold standard are imperative.}, } @article {pmid39665821, year = {2025}, author = {Serneels, PJ and De Schutter, JD and De Groef, L and Moons, L and Bergmans, S}, title = {Oligodendroglial heterogeneity in health, disease, and recovery: deeper insights into myelin dynamics.}, journal = {Neural regeneration research}, volume = {20}, number = {11}, pages = {3179-3192}, pmid = {39665821}, issn = {1673-5374}, abstract = {Decades of research asserted that the oligodendroglial lineage comprises two cell types: oligodendrocyte precursor cells and oligodendrocytes. However, recent studies employing single-cell RNA sequencing techniques have uncovered novel cell states, prompting a revision of the existing terminology. Going forward, the oligodendroglial lineage should be delineated into five distinct cell states: oligodendrocyte precursor cells, committed oligodendrocyte precursor cells, newly formed oligodendrocytes, myelin-forming oligodendrocytes, and mature oligodendrocytes. This new classification system enables a deeper understanding of the oligodendroglia in both physiological and pathological contexts. Adopting this uniform terminology will facilitate comparison and integration of data across studies. This, including the consolidation of findings from various demyelinating models, is essential to better understand the pathogenesis of demyelinating diseases. Additionally, comparing injury models across species with varying regenerative capacities can provide insights that may lead to new therapeutic strategies to overcome remyelination failure. Thus, by standardizing terminology and synthesizing data from diverse studies across different animal models, we can enhance our understanding of myelin pathology in central nervous system disorders such as multiple sclerosis, Alzheimer's disease, and amyotrophic lateral sclerosis, all of which involve oligodendroglial and myelin dysfunction.}, } @article {pmid39664805, year = {2025}, author = {Xing, H and McGregor, SKM and Batista, BD and Whitefield, C and Stone, ISJ and Murray, CE and Hurst, RM and Liu, Y and Chow, S and Fahrenhorst-Jones, T and Zhao, Q and Houston, SD and Hu, SH and Lonhienne, T and Nouwens, A and Burns, JM and Savage, GP and Walter, GH and Guddat, LW and Rafter, MA and Williams, CM}, title = {In search of herbistasis: COT-metsulfuron methyl displays rare herbistatic properties.}, journal = {Chemical science}, volume = {16}, number = {2}, pages = {649-658}, pmid = {39664805}, issn = {2041-6520}, abstract = {Weed management is an essential intervention for maintaining food security and protecting biodiversity but is heavily reliant on chemical control measures (i.e., herbicides). Concerningly, only one herbicide has been developed with a new mode of action (MOA) since the 1980s. Therefore, alternative strategies for preventing weed growth need to be explored. The lesser-known concept of halting weed growth through herbistasis could be one strategy to alleviate the lack of success in obtaining new MOA leads, but this type of activity has rarely been investigated. Herein reported is a bioisosteric cyclooctatetraene (COT) for phenyl ring replacement tactic, using the commercial acetolactate synthase (ALS) inhibitor metsulfuron methyl, that has unearthed a rare agent displaying herbistatic properties against the weed, Cryptostegia grandiflora (rubber vine).}, } @article {pmid39664295, year = {2024}, author = {Chen, LX and Zhang, MD and Xu, HF and Ye, HQ and Chen, DF and Wang, PS and Bao, ZW and Zou, SM and Lv, YT and Wu, ZY and Li, HF}, title = {Single-Nucleus RNA Sequencing Reveals the Spatiotemporal Dynamics of Disease-Associated Microglia in Amyotrophic Lateral Sclerosis.}, journal = {Research (Washington, D.C.)}, volume = {7}, number = {}, pages = {0548}, pmid = {39664295}, issn = {2639-5274}, abstract = {Disease-associated microglia (DAM) are observed in neurodegenerative diseases, demyelinating disorders, and aging. However, the spatiotemporal dynamics and evolutionary trajectory of DAM during the progression of amyotrophic lateral sclerosis (ALS) remain unclear. Using a mouse model of ALS that expresses a human SOD1 gene mutation, we found that the microglia subtype DAM begins to appear following motor neuron degeneration, primarily in the brain stem and spinal cord. Using reverse transcription quantitative polymerase chain reaction, RNAscope in situ hybridization, and flow cytometry, we found that DAM increased in number as the disease progressed, reaching their peak in the late disease stage. DAM responded to disease progression in both SOD1[G93A] mice and sporadic ALS and C9orf72-mutated patients. Motor neuron loss in SOD1[G93A] mice exhibited 2 accelerated phases: P90 to P110 (early stage) and P130 to P150 (late stage). Some markers were synchronized with the accelerated phase of motor neuron loss, suggesting that these proteins may be particularly responsive to disease progression. Through pseudotime trajectory analysis, we tracked the dynamic transition of homeostatic microglia into DAM and cluster 6 microglia. Interestingly, we used the colony-stimulating factor 1 receptor (CSF1R) inhibitor PLX5622 to deplete microglia in SOD1[G93A] mice and observed that DAM survival is independent of CSF1R. An in vitro phagocytosis assay directly confirmed that DAM could phagocytose more beads than other microglia subtypes. These findings reveal that the induction of the DAM phenotype is a shared cross-species and cross-subtype characteristic in ALS. Inducing the DAM phenotype and enhancing its function during the early phase of disease progression, or the time window between P130 and P150 where motor neuron loss slows, could serve as a neuroprotective strategy for ALS.}, } @article {pmid39663989, year = {2025}, author = {Das, U and Gayan, A and Biswas, R}, title = {A highly sensitive facile plasmonic scheme for assessment of melamine in raw milk.}, journal = {Analytical methods : advancing methods and applications}, volume = {17}, number = {3}, pages = {552-561}, doi = {10.1039/d4ay01764a}, pmid = {39663989}, issn = {1759-9679}, mesh = {*Triazines/analysis ; *Milk/chemistry ; Animals ; Metal Nanoparticles/chemistry ; Gold/chemistry ; Limit of Detection ; Silver/chemistry ; *Food Contamination/analysis ; Colorimetry/methods/instrumentation ; }, abstract = {This work presents two novel devices with a microcontroller and two different light sensors, namely, Light Dependent Resistor (LDR) and Ambient Light Sensor (ALS), which can provide a quantitative output from the colorimetric variations of citrate capped borohydride reduced silver nanoparticles (AgNPs) and citrate capped gold nanoparticles (AuNPs) upon addition of melamine adulterated milk. The limit of detection (LOD) of the LDR setup with AgNPs and AuNPs was found to be 1.24 ppm and 1.68 ppm, respectively, and the corresponding recovery rates were 92.86% and 88.57%, respectively. The device fabricated with the ALS with AgNPs displayed a recovery rate of 97.14% with a LOD value of 0.64 ppm.}, } @article {pmid39662855, year = {2025}, author = {Yang, ZF and Jiang, XC and Gao, JQ}, title = {Present insights into the progress in gene therapy delivery systems for central nervous system diseases.}, journal = {International journal of pharmaceutics}, volume = {669}, number = {}, pages = {125069}, doi = {10.1016/j.ijpharm.2024.125069}, pmid = {39662855}, issn = {1873-3476}, mesh = {Humans ; *Genetic Therapy/methods ; *Central Nervous System Diseases/therapy ; Animals ; *Gene Transfer Techniques ; *Genetic Vectors/administration & dosage ; Dependovirus/genetics ; }, abstract = {Central nervous system (CNS) diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), spinal cord injury (SCI), and ischemic strokes and certain rare diseases, such as amyotrophic lateral sclerosis (ALS) and ataxia, present significant obstacles to treatment using conventional molecular pharmaceuticals. Gene therapy, with its ability to target previously "undruggable" proteins with high specificity and safety, is increasingly utilized in both preclinical and clinical research for CNS ailments. As our comprehension of the pathophysiology of these conditions deepens, gene therapy stands out as a versatile and promising strategy with the potential to both prevent and treat these diseases. Despite the remarkable progress in refining and enhancing the structural design of gene therapy agents, substantial obstacles persist in their effective and safe delivery within living systems. To surmount these obstacles, a diverse array of gene delivery systems has been devised and continuously improved. Notably, Adeno-Associated Virus (AAVs)-based viral gene vectors and lipid-based nanocarriers have each advanced the in vivo delivery of gene therapies to various extents. This review aims to concisely summarize the pathophysiological foundations of CNS diseases and to shed light on the latest advancements in gene delivery vector technologies. It discusses the primary categories of these vectors, their respective advantages and limitations, and their specialized uses in the context of gene therapy delivery.}, } @article {pmid39662651, year = {2025}, author = {Keethedeth, N and Anantha Shenoi, R}, title = {Mitochondria-targeted nanotherapeutics: A new frontier in neurodegenerative disease treatment.}, journal = {Mitochondrion}, volume = {81}, number = {}, pages = {102000}, doi = {10.1016/j.mito.2024.102000}, pmid = {39662651}, issn = {1872-8278}, mesh = {Humans ; *Neurodegenerative Diseases/drug therapy ; *Mitochondria/drug effects/metabolism ; Animals ; *Drug Delivery Systems/methods ; Nanoparticles ; }, abstract = {Mitochondria are the seat of cellular energy and play key roles in regulating several cellular processes such as oxidative phosphorylation, respiration, calcium homeostasis and apoptotic pathways. Mitochondrial dysfunction results in error in oxidative phosphorylation, redox imbalance, mitochondrial DNA mutations, and disturbances in mitochondrial dynamics, all of which can lead to several metabolic and degenerative diseases. A plethora of studies have provided evidence for the involvement of mitochondrial dysfunction in the pathogenesis of neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease, Huntington's disease, and amyotrophic lateral sclerosis. Hence mitochondria have been used as possible therapeutic targets in the regulation of neurodegenerative diseases. However, the double membranous structure of mitochondria poses an additional barrier to most drugs even if they are able to cross the plasma membrane. Most of the drugs acting on mitochondria also required very high doses to exhibit the desired mitochondrial accumulation and therapeutic effect which in-turn result in toxic effects. Mitochondrial targeting has been improved by direct conjugation of drugs to mitochondriotropic molecules like dequalinium (DQA) and triphenyl phosphonium (TPP) cations. But being cationic in nature, these molecules also exhibit toxicity at higher doses. In order to further improve the mitochondrial localization with minimal toxicity, TPP was conjugated with various nanomaterials like liposomes. inorganic nanoparticles, polymeric nanoparticles, micelles and dendrimers. This review provides an overview of the role of mitochondrial dysfunction in neurodegenerative diseases and various nanotherapeutic strategies for efficient targeting of mitochondria-acting drugs in these diseases.}, } @article {pmid40225153, year = {2023}, author = {Fiorini, MR and Dilliott, AA and Farhan, SMK}, title = {Evaluating the Utility of REVEL and CADD for Interpreting Variants in Amyotrophic Lateral Sclerosis Genes.}, journal = {Human mutation}, volume = {2023}, number = {}, pages = {8620557}, pmid = {40225153}, issn = {1098-1004}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/diagnosis ; *Computational Biology/methods ; *Genetic Predisposition to Disease ; *Genetic Variation ; *Software ; Genetic Association Studies ; Mutation ; Databases, Genetic ; Genetic Testing ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a debilitating neurodegenerative disease affecting approximately two per 100,000 individuals globally. While there are many benefits to offering early genetic testing to people with ALS, this has also led to an increase in the yield of novel variants of uncertain significance in ALS-associated genes. Computational (in silico) predictors, including REVEL and CADD, are widely employed to provide supporting evidence of pathogenicity for variants in conjunction with clinical, molecular, and other genetic evidence. However, in silico predictors are developed to be broadly applied across the human genome; thus, their ability to evaluate the consequences of variation in ALS-associated genes remains unclear. To resolve this ambiguity, we surveyed 20 definitive and moderate ClinGen-defined ALS-associated genes from two large, open-access ALS sequencing datasets (total people with ALS = 8,230; controls = 9,671) to investigate REVEL and CADD's ability to predict which variants are most likely to be disease-causing in ALS. While our results indicate a predetermined pathogenicity threshold for REVEL that could be of clinical value for classifying variants in ALS-associated genes, an accurate threshold was not evident for CADD, and both in silico predictors were of limited value for resolving which variants of uncertain significance (VUS) may be likely pathogenic in ALS. Our findings allow us to provide important recommendations for the use of REVEL and CADD scores for variants and indicate that both tools should be used with caution when attempting to evaluate the pathogenicity of VUSs in ALS genetic testing.}, } @article {pmid40098659, year = {2023}, author = {Serrano-Giraldo, J and Becerra-Muñoz, MP and Tijaro-Santos, JA and Zarante, I}, title = {[Current situation of rare diseases in Bogotá: Notification to Sivigila from 2019 to 2022].}, journal = {Revista de salud publica (Bogota, Colombia)}, volume = {25}, number = {4}, pages = {107594}, pmid = {40098659}, issn = {2539-3596}, abstract = {OBJECTIVE: To analyze the reports of orphan diseases in Bogotá, in order to describe the epidemiological profile, based on the cases reported to the Public Health System (Sivigila), from January 2019 to March 2022.

METHODS: A descriptive and cross-sectional study was carried out in which the cases reported to Sivigila in Bogotá were analyzed in the period between January 2019 and March 2022. Absolute and relative frequencies, frequency distribution and prevalences and averages of different variables were calculated. notified in the notification sheets.

RESULTS: From January 2019 to March 2022, 10,399 patients with orphan diseases have been notified to Sivigila in Bogotá, of which 56.25% (5,849) are female and 43.75% (4,550) are female. male sex. 87.10% (9,060) of the cases belong to the contributory regime. The town with the highest number of reports was Suba with 15.85% (1,294). The most reported orphan diseases were: multiple sclerosis with 13.1% (1,363), amyotrophic lateral sclerosis with 4.04% (421) and Guillain-Barre syndrome with 3.6% (374). A patient with an orphan disease in Bogotá takes 61.3 months on average from the beginning of their symptoms to obtaining a diagnosis (SD 101.9).

CONCLUSIONS: From the notification to Sivigila in Bogotá, compared to the global prevalence, there is an under-registration of patients with orphan diseases and the delay in the diagnosis of these diseases is evident.}, } @article {pmid39872952, year = {2023}, author = {Wang, J and Zhou, XF and Wang, YJ}, title = {Continuous antioxidant drug exposure: a bridge from ideal world to real world of therapy for amyotrophic lateral sclerosis.}, journal = {Life medicine}, volume = {2}, number = {1}, pages = {lnac042}, pmid = {39872952}, issn = {2755-1733}, } @article {pmid39657109, year = {2025}, author = {Benatar, M and McDermott, C and Turner, MR and van Eijk, RPA}, title = {Rethinking phase 2 trials in amyotrophic lateral sclerosis.}, journal = {Brain : a journal of neurology}, volume = {148}, number = {4}, pages = {1106-1111}, pmid = {39657109}, issn = {1460-2156}, support = {/NH/NIH HHS/United States ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy/drug therapy ; *Clinical Trials, Phase II as Topic/methods ; }, abstract = {There is a long history in amyotrophic lateral sclerosis (ALS) of promoting therapies based on phase 2 data, which then fail in phase 3 trials. Experience suggests that studies of 6 months in duration are too short, especially with function-based outcome measures. Multiplicity poses a serious threat to data interpretation, and strategies to impute missing data may not be appropriate for ALS where progression is always expected. Emerging surrogate markers of clinical benefit such as reduction of neurofilament light chain levels may be better suited to phase 2 go/no-go decisions. Over-interpretation of phase 2 data, and overly optimistic communication of exploratory analyses must be avoided to ensure optimal prioritization for the investment needed for definitive phase 3 trials and to minimize the harm of false hope for people living with ALS. Delivering on advances in understanding of the neurobiology of ALS requires urgent attention to phase 2 design and implementation.}, } @article {pmid39656857, year = {2024}, author = {Alvarado, M and Gómez-Navajas, JA and Blázquez-Muñoz, MT and Gómez-Molero, E and Fernández-Sánchez, S and Eraso, E and Munro, CA and Valentín, E and Mateo, E and de Groot, PWJ}, title = {The good, the bad, and the hazardous: comparative genomic analysis unveils cell wall features in the pathogen Candidozyma auris typical for both baker's yeast and Candida.}, journal = {FEMS yeast research}, volume = {24}, number = {}, pages = {}, pmid = {39656857}, issn = {1567-1364}, support = {PID2020-117983RB-I00//Agencia Estatal de Investigación/ ; SBPLY/23/180225/000029//UCLM/ ; //European Regional Development Fund/ ; JDC2023-051226-I//European Social Fund Plus/ ; }, mesh = {*Cell Wall/metabolism ; *Saccharomyces cerevisiae/genetics/metabolism ; Computational Biology ; Genomics ; Candida auris/genetics/metabolism/drug effects ; beta-Glucans/metabolism ; Genome, Fungal ; Fungal Proteins/genetics/metabolism ; Glycosylphosphatidylinositols/metabolism/genetics ; Candida albicans/genetics/pathogenicity ; Candida/genetics/metabolism/pathogenicity ; }, abstract = {The drug-resistant pathogenic yeast Candidozyma auris (formerly named Candida auris) is considered a critical health problem of global importance. As the cell wall plays a crucial role in pathobiology, here we performed a detailed bioinformatic analysis of its biosynthesis in C. auris and related Candidozyma haemuli complex species using Candida albicans and Saccharomyces cerevisiae as references. Our data indicate that the cell wall architecture described for these reference yeasts is largely conserved in Candidozyma spp.; however, expansions or reductions in gene families point to subtle alterations, particularly with respect to β--1,3--glucan synthesis and remodeling, phosphomannosylation, β-mannosylation, and glycosylphosphatidylinositol (GPI) proteins. In several aspects, C. auris holds a position in between C. albicans and S. cerevisiae, consistent with being classified in a separate genus. Strikingly, among the identified putative GPI proteins in C. auris are adhesins typical for both Candida (Als and Hyr/Iff) and Saccharomyces (Flo11 and Flo5-like flocculins). Further, 26 putative C. auris GPI proteins lack homologs in Candida genus species. Phenotypic analysis of one such gene, QG37_05701, showed mild phenotypes implicating a role associated with cell wall β-1,3-glucan. Altogether, our study uncovered a wealth of information relevant for the pathogenicity of C. auris as well as targets for follow-up studies.}, } @article {pmid39656589, year = {2024}, author = {Nascimento, F and Özyurt, MG and Halablab, K and Bhumbra, GS and Caron, G and Bączyk, M and Zytnicki, D and Manuel, M and Roselli, F and Brownstone, R and Beato, M}, title = {Spinal microcircuits go through multiphasic homeostatic compensations in a mouse model of motoneuron degeneration.}, journal = {Cell reports}, volume = {43}, number = {12}, pages = {115046}, pmid = {39656589}, issn = {2211-1247}, support = {/WT_/Wellcome Trust/United Kingdom ; R01 NS110953/NS/NINDS NIH HHS/United States ; 221610/Z/20/Z/WT_/Wellcome Trust/United Kingdom ; MR/V003607/1/MRC_/Medical Research Council/United Kingdom ; BB/S005943/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Animals ; *Motor Neurons/metabolism/pathology ; Mice ; *Homeostasis ; *Disease Models, Animal ; *Spinal Cord/pathology/metabolism ; Synaptic Transmission/physiology ; Receptors, Glycine/metabolism ; Nerve Degeneration/pathology ; Mice, Inbred C57BL ; Renshaw Cells/metabolism ; }, abstract = {In many neurological conditions, early-stage neural circuit adaptation preserves relatively normal behavior. In some diseases, spinal motoneurons progressively degenerate yet movement remains initially preserved. This study investigates whether these neurons and associated microcircuits adapt in a mouse model of progressive motoneuron degeneration. Using a combination of in vitro and in vivo electrophysiology and super-resolution microscopy, we find that, early in the disease, neurotransmission in a key pre-motor circuit, the recurrent inhibition mediated by Renshaw cells, is reduced by half due to impaired quantal size associated with decreased glycine receptor density. This impairment is specific and not a widespread feature of spinal inhibitory circuits. Furthermore, it recovers at later stages of disease. Additionally, an increased probability of release from proprioceptive afferents leads to increased monosynaptic excitation of motoneurons. We reveal that, in this motoneuron degenerative condition, spinal microcircuits undergo specific multiphasic homeostatic compensations that may contribute to preservation of force output.}, } @article {pmid39662532, year = {2025}, author = {Bayansan, O and Bhan, P and Chang, CY and Barmaver, SN and Shen, CP and Wagner, OI}, title = {UNC-10/SYD-2 links kinesin-3 to RAB-3-containing vesicles in the absence of the motor's PH domain.}, journal = {Neurobiology of disease}, volume = {204}, number = {}, pages = {106766}, doi = {10.1016/j.nbd.2024.106766}, pmid = {39662532}, issn = {1095-953X}, mesh = {Animals ; *Caenorhabditis elegans Proteins/metabolism/genetics ; *Caenorhabditis elegans/metabolism ; *rab3 GTP-Binding Proteins/metabolism/genetics ; *Synaptic Vesicles/metabolism ; Kinesins/metabolism/genetics ; Intracellular Signaling Peptides and Proteins/metabolism/genetics ; Animals, Genetically Modified ; Pleckstrin Homology Domains ; Nerve Tissue Proteins ; Intercellular Signaling Peptides and Proteins ; }, abstract = {Kinesin-3 KIF1A (UNC-104 in C. elegans) is the major axonal transporter of synaptic vesicles and mutations in this molecular motor are linked to KIF1A-associated neurological disorders (KAND), encompassing Charcot-Marie-Tooth disease, amyotrophic lateral sclerosis and hereditary spastic paraplegia. UNC-104 binds to lipid bilayers of synaptic vesicles via its C-terminal PH (pleckstrin homology) domain. Since this interaction is relatively weak and non-specific, we hypothesize that other, more specific, interaction schemes exist. From the literature, it is evident that UNC-104 regulator SYD-2 interacts with UNC-10 and that UNC-10 itself interacts with RAB-3 bound to synaptic vesicles. RT-PCR and Western blot experiments expose genetic relationships between unc-10 and syd-2, but not between unc-10 and rab-3. Also, neither unc-10 nor rab-3 affects UNC-104 expression. However, co-immunoprecipitation and bimolecular fluorescence complementation (BiFC) assays reveal functional interactions between UNC-104, SYD-2, UNC-10 and RAB-3. Though both SNB-1 and RAB-3 are actively transported by UNC-104, motility of RAB-3 is facilitated in the presence of SYD-2 and UNC-10. Deletion of UNC-104's PH domain did not affect UNC-104/RAB-3 colocalization, but significantly affected UNC-104/SNB-1 colocalization. Similarly, motility of RAB-3-labeled vesicles is only slightly altered in nematodes carrying a point mutation in the PH domain, whereas movement of SNB-1 is significantly reduced in this mutant. Western blots from purified fractions of synaptic vesicles reveal strong reduction of UNC-104 in rab-3/unc-10 double mutants. Our findings suggest that the UNC-10/SYD-2 complex acts as a functional linker to connect UNC-104 to RAB-3-containing vesicles. Thus, this linker complex contributes to the specificity of motor/cargo interactions.}, } @article {pmid39662462, year = {2025}, author = {Huang, C and Qiu, L and Zhou, W and Shao, C and Wang, X and Zhang, Q and Chen, W and Xiong, M and Huang, M and Tang, M and Zou, L and Xu, X}, title = {A human-induced pluripotent stem cell (iPSC) line (SMUSHi006-A) from an ALS patient carrying a mutation c.1126C > T in the FUS gene.}, journal = {Stem cell research}, volume = {82}, number = {}, pages = {103604}, doi = {10.1016/j.scr.2024.103604}, pmid = {39662462}, issn = {1876-7753}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/pathology/metabolism ; *RNA-Binding Protein FUS/genetics/metabolism ; *Induced Pluripotent Stem Cells/metabolism/pathology/cytology ; *Mutation ; Cell Line ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease. Four major genes associated with ALS-SOD1, TARDBP, FUS, and C9orf72-have been identified, with the fused in sarcoma (FUS) gene demonstrating considerable genetic heterogeneity. Our research group has previously established an induced pluripotent stem (iPS) cell line harboring the c.1562G > A mutation in the FUS gene. The objective of this study is to create another iPS cell line featuring the pathogenic c.1126C > T mutation in the FUS gene. This research aims not only to establish a disease model for ALS linked to FUS mutations but also to pave the way for potential therapeutic interventions.}, } @article {pmid39660938, year = {2025}, author = {Kashiwagi-Hakozaki, M and Ikemura, M and Naruse, H and Takahashi, Y and Toda, T and Ushiku, T}, title = {An autopsy case report of amyotrophic lateral sclerosis with unusual basophilic inclusions exhibiting immunopositivity for optineurin.}, journal = {Pathology international}, volume = {75}, number = {2}, pages = {121-123}, doi = {10.1111/pin.13501}, pmid = {39660938}, issn = {1440-1827}, } @article {pmid39659975, year = {2024}, author = {Kim, HJ and Ban, JJ and Kang, J and Im, HR and Ko, SH and Sung, JJ and Park, SH and Park, JE and Choi, SJ}, title = {Single-cell analysis reveals expanded CD8[+] GZMK [high] T cells in CSF and shared peripheral clones in sporadic amyotrophic lateral sclerosis.}, journal = {Brain communications}, volume = {6}, number = {6}, pages = {fcae428}, pmid = {39659975}, issn = {2632-1297}, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that affects motor neurons in the brain and spinal cord. Despite the crucial role of aberrant immune responses in ALS pathogenesis, studies investigating immunological profiles in the cerebrospinal fluid (CSF) of patients with ALS have reported inconsistent findings. Herein, we explored the intrathecal adaptive immune response and features of circulating T cells between CSF and blood of patients with ALS using single-cell RNA and T-cell receptor (TCR) sequencing. This study comprised a total of 11 patients with apparently sporadic ALS and three controls with non-inflammatory diseases. We collected CSF from all participants, and for three patients with ALS, we additionally obtained paired samples of peripheral blood mononuclear cells (PBMCs). Utilizing droplet-based single-cell RNA and TCR sequencing, we analysed immunological profiles, gene expression characteristics and clonality. Furthermore, we examined T-cell characteristics in both PBMC and CSF samples, evaluating the shared T-cell clones across these compartments. In the CSF, patients with ALS exhibited a lower proportion of CD4[+] T cells (45.2 versus 61.2%, P = 0.005) and a higher proportion of CD8[+] GZMK [hi] effector memory T cells (TEMs) than controls (21.7 versus 16.8%, P = 0.060). Higher clonality was observed in CD8[+] TEMs in patients with ALS compared with controls. In addition, CSF macrophages of patients with ALS exhibited a significant increase in chemokines recruiting CD8[+] TEMs. Immunohistochemical analysis showed slightly higher proportions of T cells in the perivascular and parenchymal spaces in patients with ALS than in controls, and CD8[+] TEMs co-localized with neurons or astrocytes in the motor cortices of patients with ALS. Clonally expanded CD8[+] GZMK [hi] TEMs primarily comprised shared T-cell clones between CSF and PBMCs. Moreover, the shared CD8[+] TEMs of PBMCs exhibited gene expression profiles similar to CSF T cells. Patients with ALS showed an increase in proportion and clonality of CD8[+] GZMK [hi] TEMs and activated features of macrophages in CSF. The shared T-cell clone between CSF and blood was mainly composed of expanded CD8[+] GZMK [hi] TEMs. In conclusion, single-cell immune profiling provided novel insights into the pathogenesis of ALS, characterized by activated macrophages and clonally expanded CD8[+] T cells potentially communicating with the central nervous system and peripheral circulation.}, } @article {pmid39659885, year = {2024}, author = {Wan, H and Qian, W and Wei, B and Tian, K and Chen, Z and Zhang, J and Chen, F}, title = {A bibliometric analysis of gene editing and amyotrophic lateral sclerosis (from 2004 to 2024).}, journal = {Frontiers in neuroscience}, volume = {18}, number = {}, pages = {1499025}, pmid = {39659885}, issn = {1662-4548}, abstract = {OBJECTIVE: To learn more about gene editing and ALS, and to provide a comprehensive view of gene editing for further treatment of amyotrophic lateral sclerosis.

METHODS: We searched 1981 records from Web of Science core collection and Pubmed, Scopus, of which 1,292 records were obtained after exclusion. We then scientifically and metrologically analyzed these records for spatial and temporal distribution, author distribution, subject categories, subject distribution, references, and keywords using R, software CiteSpace and VOSviewer.

RESULTS: Our analysis provides basic information about research in the field, suggests that the field has stabilized over the past decade, and identifies potential partners for interested researchers. Current research in this area is focused on inflammatory mechanisms, immune mechanisms, related diseases, and associated cytokines in ALS.

CONCLUSION: RNA Editing, Antisense Bligonucleotide, and Glycine Receptor are cutting-edge research topics in this field, which is undergoing rapid development. We hope that this work will provide new ideas for advancing the scientific research and clinical application of ALS.}, } @article {pmid39659205, year = {2024}, author = {Alzahrani, AK and A S, A and Imran, M}, title = {Unraveling the molecular mechanisms of ALS: a network biology and structural modeling approach of investigating the impact of C9orf72 mutations.}, journal = {Journal of biomolecular structure & dynamics}, volume = {}, number = {}, pages = {1-14}, doi = {10.1080/07391102.2024.2437682}, pmid = {39659205}, issn = {1538-0254}, abstract = {C9orf72 is a major genetic factor in Amyotrophic Lateral Sclerosis (ALS), a neurodegenerative disorder affecting brain and spinal cord neurons, and comprehending its mutational impact is crucial for developing ALS therapies. Therefore, the current study's protein-protein interaction (PPI) network for C9orf72 was meticulously mapped to identify key interactors that might influence the disease mechanism. Among the identified proteins, SMCR8 emerged as a prominent candidate due to its high connectivity (total network contribution = 7.896) within the C9orf72-associated network, suggesting a potential role in modulating the effects of C9orf72 mutations. Analysis of C9orf72 mutations highlighted the I525T mutation, which significantly destabilizes the protein, as indicated by a ΔΔG value of -2.02 kcal/mol. Further investigation involved comparing the structural dynamics of the wild-type C9orf72 and its mutant variants through molecular docking and dynamics simulations. The wild-type demonstrated more stable structural conformation over time, as shown by its RMSD profile than its mutant counterpart. However, after 80 nanoseconds, the mutant variant achieved a similar RMSD stability level. Intriguingly, the mutant formed a more stable complex with SMCR8, evident from its lower binding free energy (-64.18 kcal/mol compared to the wild type's -34.82 kcal/mol). Moreover, per-residue decomposition analysis further revealed critical interactions at specific residues. The wild-type protein showed a significant stabilizing interaction at Arg785, whereas the mutant favored Arg262, indicating a potential shift in binding affinity and site due to the mutation. This shift suggests an altered binding landscape in the mutant C9orf72, which might contribute to the dysregulated protein interactions and cellular processes associated with ALS pathology. The study thus underscores the pathological hyper-stability of the mutant C9orf72, highlighting its potential role in the progression of ALS.}, } @article {pmid39656022, year = {2024}, author = {Prentiss, AM and Baggio, C and Pagett, J and Kulinich, AO and Ethell, IM and Muzzarelli, K and Assar, Z and Pellecchia, M}, title = {Constrained β-Hairpins Targeting the EphA4 Ligand Binding Domain.}, journal = {Journal of medicinal chemistry}, volume = {67}, number = {24}, pages = {22245-22253}, pmid = {39656022}, issn = {1520-4804}, support = {R01 CA168517/CA/NCI NIH HHS/United States ; P41 GM103311/GM/NIGMS NIH HHS/United States ; R01 NS129555/NS/NINDS NIH HHS/United States ; P20 CA242620/CA/NCI NIH HHS/United States ; R01 NS107479/NS/NINDS NIH HHS/United States ; }, mesh = {*Receptor, EphA4/metabolism/antagonists & inhibitors/chemistry ; Ligands ; Humans ; Binding Sites ; Protein Binding ; Peptides, Cyclic/chemistry/pharmacology/metabolism/chemical synthesis ; Drug Design ; Protein Domains/drug effects ; Models, Molecular ; }, abstract = {The activity of the receptor tyrosine kinase EphA4 has been implicated in several pathologies including oncology (gastric and pancreatic cancers) and neurodegenerative diseases (amyotrophic lateral sclerosis and Alzheimer's disease). However, advances in validating EphA4 as a possible drug target have been limited by the lack of suitable pharmacological inhibitors. Recently, we reported on the design of potent EphA4 agonistic agents targeting its ligand binding domain (LBD). Based on previous studies with a phage display cyclic peptide inhibitor, we designed a β-hairpin mimetic with high affinity for EphA4-LBD. These agents hold great promise for further validation and development of EphA4-based therapeutics. Moreover, our studies introduce a possible strategy for the design of constrained β-hairpin peptides.}, } @article {pmid39655696, year = {2025}, author = {Di Iacovo, A and D'Agostino, C and Bhatt, M and Romanazzi, T and Giovannardi, S and Cinquetti, R and Roseti, C and Bossi, E}, title = {The kinase LRRK2 is required for the physiological function and expression of the glial glutamate transporter EAAT2 (SLC1A2).}, journal = {Journal of neurochemistry}, volume = {169}, number = {1}, pages = {e16265}, pmid = {39655696}, issn = {1471-4159}, support = {860954//H2020 Marie Skłodowska-Curie Actions/ ; }, mesh = {Animals ; *Leucine-Rich Repeat Serine-Threonine Protein Kinase-2/genetics/metabolism/biosynthesis ; *Excitatory Amino Acid Transporter 2/metabolism/genetics/biosynthesis ; *Xenopus laevis ; Humans ; Oocytes/metabolism ; Female ; Neuroglia/metabolism ; }, abstract = {Neurotransmitter transporters (NTTs) control synaptic responses by modulating the concentration of neurotransmitters at the synaptic cleft. Glutamate is the most abundant excitatory neurotransmitter in the brain and needs to be finely tuned in time and space to maintain a healthy brain and precise neurotransmission. The glutamate transporter EAAT2 (SLC1A2) is primarily responsible for glutamate clearance. EAAT2 impairment has been associated with Alzheimer's disease (AD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), and Parkinson's disease (PD). Mutations in leucine-rich repeat kinase 2 (LRRK2) contribute to both monogenic and sporadic forms of PD, of which the common substitution Gly2019Ser is associated with a significant deficit in EAAT2 expression. The role of pathological mutants of the LRRK2 is intensively studied and reviewed. Here we have focused the attention on the physiological role of LRRK2 on EAAT2, comparing the activity of NTTs with or without the LRRK2 kinase. By heterologous expression in Xenopus laevis oocytes and two-electrode voltage clamp, the current amplitudes of the selected NTTs and kinetic parameters have been collected in the presence and absence of LRRK2. The results show that EAAT2 expression and function are impaired in the absence of the kinase and also under its pharmacological inhibition via MLi-2 treatment. LRRK2 stabilizes EAAT2 expression increasing the amount of transporter at the plasma membrane. Interestingly, the LRRK2 action is EAAT2-specific, as we observed no significant changes in the transport current amplitude and kinetic parameters obtained for the other excitatory and inhibitory NTTs studied. This study, for the first time, demonstrates the physiological importance of LRRK2 in EAAT2 function, highlighting the specificity of LRRK2-mediated modulation of EAAT2 and suggesting a potential role for the kinase as a checkpoint for preserving neurons from excitotoxicity. In brain conditions associated with impaired glutamate clearance, targeting LRRK2 for EAAT2 regulation may offer novel therapeutic opportunities.}, } @article {pmid39655539, year = {2025}, author = {Canosa, A and Martino, A and Manera, U and Giuliani, A and Vasta, R and Palumbo, F and Grassano, M and Morbelli, SD and Pardini, M and Chiaravalloti, A and Schillaci, O and Leenders, KL and Kogan, RV and Polverari, G and Zocco, G and Pede, FD and Mattei, F and Cabras, S and Matteoni, E and Moglia, C and Calvo, A and Chiò, A and Pagani, M}, title = {Sex-related differences in amyotrophic lateral sclerosis: A 2-[[18]F]FDG-PET study.}, journal = {European journal of neurology}, volume = {32}, number = {1}, pages = {e16588}, pmid = {39655539}, issn = {1468-1331}, support = {//Dipartimenti di Eccellenza/ ; RF-2016- 02362405//Ministero della Salute/ ; 259867//Seventh Framework Programme/ ; 2017SNW5MB//Ministero dell'Università e della Ricerca/ ; //Fondation Thierry Latran/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnostic imaging/metabolism ; Male ; Female ; Middle Aged ; *Positron-Emission Tomography ; *Fluorodeoxyglucose F18 ; Aged ; *Sex Characteristics ; *Brain/diagnostic imaging/metabolism ; Adult ; }, abstract = {PURPOSE: We investigated sex-related brain metabolic differences in Amyotrophic Lateral Sclerosis (ALS) and healthy controls (HC).

METHODS: We collected two equal-sized groups of male (m-ALS) and female ALS (f-ALS) patients (n = 130 each), who underwent 2-[[18]F]FDG-PET at diagnosis, matched for site of onset, cognitive status and King's stage. We included 168 age-matched healthy controls, half female (f-HC) and half male (m-HC). We compared brain metabolism of males and females separately for ALS and HC, including age as covariate. A differential network analysis was performed to evaluate brain connectivity.

RESULTS: M-ALS showed relative hypometabolism of bilateral medial frontal, parietal and occipital cortices, and left temporal cortex, compared to f-ALS. In node-wise comparison, f-ALS showed significantly higher connectivity in right middle cingulate cortex and left superior and medial frontal gyrus. In HC we did not find any sex-related differences.

CONCLUSION: Sex resulted a major determinant of brain metabolism and connectivity in ALS patients.}, } @article {pmid39655175, year = {2024}, author = {Palm, A and Ekström, M and Emilsson, Ö and Ersson, K and Ljunggren, M and Sundh, J and Grote, L}, title = {Control of hypercapnia and mortality in home mechanical ventilation: the population-based DISCOVERY study.}, journal = {ERJ open research}, volume = {10}, number = {6}, pages = {}, pmid = {39655175}, issn = {2312-0541}, abstract = {BACKGROUND: Studies on the survival of patients with home mechanical ventilation (HMV) are sparse. We aimed to analyse the impact of controlled hypercapnia on survival over 27 years among patients with HMV in Sweden.

STUDY DESIGN AND METHODS: Population-based cohort study of adult patients starting HMV in the Swedish Registry for Respiratory Failure (Swedevox) during 1996-2022 cross-linked with the National Cause of Death registry. Mortality risk factors were analysed using crude and multivariable Cox regression models, including adjustments for anthropometrics, comorbidities, the underlying diagnosis causing chronic hypercapnic respiratory failure (CRF) and the control of hypercapnia (P aCO2 ≤6.0 kPa) at follow-up.

RESULTS: We included 10 190 patients (50.1% women, age 62.9±14.5 years). Control of hypercapnia at follow-up after 1.3±0.9 years was associated with lower mortality, hazard ratio (HR) 0.74 (95% CI 0.68-0.80) and the association was strongest in those with pulmonary disease, restrictive thoracal disease (RTD), obesity hypoventilation syndrome (OHS) and amyotrophic lateral sclerosis (ALS). Predictors for increased mortality included age, Charlson Comorbidity Index, supplemental oxygen therapy and acute start of HMV therapy. Median survival varied between 0.8 years (95% CI 0.8-0.9 (n=1401)) for ALS and 7.6 years (95% CI 6.9-8.6 (n=1061)) for neuromuscular disease. Three-year survival decreased from 76% (95% CI 71-80) between 1996 and 1998 to 52% (95% CI 50-55) between 2017 and 2019. When adjusting for underlying diagnosis and age, the association between start year and decreased survival disappeared, HR 1.00 (95% CI 0.99-1.01).

CONCLUSION: Controlling P aCO2 is a key treatment goal for survival in HMV therapy. Survival differed markedly between diagnosis and age groups, and survival rates have declined as the patient group has aged.}, } @article {pmid39655131, year = {2024}, author = {Mori, Y and Kenzaka, T}, title = {Systemic Amyloid Light Chain Amyloidosis With Repeated Syncope Due to Severe Orthostatic Hypotension Caused by Autonomic Neuropathy: A Case Report.}, journal = {Cureus}, volume = {16}, number = {11}, pages = {e73320}, pmid = {39655131}, issn = {2168-8184}, abstract = {Amyloid light chain (AL) amyloidosis is a disease in which ALs, which are proteins with fibrous structures, are deposited in systemic organs, causing functional impairment. Diagnosis is often difficult because of non-specific and varied symptoms. We report a case of systemic AL amyloidosis that was diagnosed as a result of repeated syncope. A 76-year-old woman was brought to the emergency room with multiple episodes of loss of consciousness over the past five years. She visited the major hospital, where pulmonary thromboembolism and symptomatic epilepsy were considered possible causes. Orthostatic hypotension was observed after being transferred to our hospital for rehabilitation. We performed diagnostic tests, including blood tests, imaging, and a head-up tilt test, which confirmed severe orthostatic hypotension. A gastrointestinal biopsy with Congo red staining confirmed the presence of amyloid deposits. AL amyloidosis (λ) was diagnosed using immunohistochemical staining. Given her age and prolonged bed rest, she was determined that she could not tolerate chemotherapy and was discharged upon her request. To the best of our knowledge, this is the first report of systemic AL amyloidosis presenting with orthostatic hypotension severe enough to cause syncope due to autonomic neuropathy. Autonomic neuropathy should be considered, and amyloidosis should be included in the differential diagnosis when a patient presents with recurrent syncope.}, } @article {pmid39654963, year = {2024}, author = {Sun, P and Niu, L and He, P and Yu, H and Chen, J and Cui, H and Li, X}, title = {Trp-574-Leu and the novel Pro-197-His/Leu mutations contribute to penoxsulam resistance in Echinochloa crus-galli (L.) P. Beauv.}, journal = {Frontiers in plant science}, volume = {15}, number = {}, pages = {1488976}, pmid = {39654963}, issn = {1664-462X}, abstract = {Recently, due to the widespread use of the acetolactate synthase (ALS)-inhibiting herbicide penoxsulam in paddy fields in China, Echinochloa crus-galli (L.) P. Beauv. has become a problematic grass weed that is frequently not controlled, posing a threat to weed management and rice yield. There are many reports on target-site mutations of ALS inhibiting herbicides; however, the detailed penoxsulam resistance mechanism in E. crus-galli remains to be determined. Greenhouse and laboratory studies were conducted to characterize target-site resistance mechanisms in JL-R, AH-R, and HLJ-R suspected resistant populations of E. crus-galli survived the field-recommended dose of penoxsulam. The whole-plant dose-response testing of E. crus-galli to penoxsulam confirmed the evolution of moderate-level resistance in two populations, JL-R (9.88-fold) and HLJ-R (8.66-fold), and a high-level resistance in AH-R (59.71-fold) population. ALS gene sequencing identified specific mutations in resistant populations, including Pro-197-His in ALS1 for JL-R, Trp-574-Leu in ALS1 for AH-R, and Pro-197-Leu in ALS2 for HLJ-R. In vitro ALS activity assays demonstrated a significantly higher activity in AH-R compared to the susceptible population (YN-S). Molecular docking studies revealed that Trp-574-Leu mutation primarily reduced the enzyme's ability to bind to the triazole-pyrimidine ring of penoxsulam due to decreased π-π stacking interactions, while Pro-197-His/Leu mutations impaired binding to the benzene ring by altering hydrogen bonds and hydrophobic interactions. Additionally, the Pro-197-His/Leu amino acid residue changes resulted in alterations in the shape of the active channel, impeding the efficient entry of penoxsulam into the binding site in the ALS protein. The three mutant ALS proteins expressed via the Bac-to-Bac baculovirus system exhibited notably lower activity inhibition rates than the non-mutant ALS proteins to penoxsulam, indicating all three ALS mutations reduce sensitivity to penoxsulam. This study elucidated the distinct impacts of the Pro-197-His/Leu and Trp-574-Leu mutations in E. crus-galli to penoxsulam resistance. Notably, the Trp-574-Leu mutation conferred stronger resistance to penoxsulam compared to the Pro-197-His/Leu mutations in E. crus-galli. The Pro-197-His/Leu mutations were first detected in E. crus-galli conferring penoxsulam resistance. These findings provide deeper insights into the molecular mechanisms underlying target-site resistance to penoxsulam in E. crus-galli.}, } @article {pmid39654532, year = {2025}, author = {Dave, KD and Oskarsson, B and Yersak, J and Krauss, R and Heiman-Patterson, T and Lomen-Hoerth, C and Selig, WKD and Halpern Paul, I and Schaeffer, M and Garcia-Trujillo, B and Waldo, D and Thakur, N and Babu, S}, title = {Contributions of neurologists to diagnostic timelines of ALS and thinkALS as an early referral instrument for clinicians.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {26}, number = {3-4}, pages = {215-224}, doi = {10.1080/21678421.2024.2432034}, pmid = {39654532}, issn = {2167-9223}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis ; *Referral and Consultation ; *Neurologists ; United States ; Male ; Female ; Medicare ; Aged ; Time Factors ; Delayed Diagnosis ; }, abstract = {Objectives: To evaluate neurologists and other clinicians' contributions to U.S. ALS diagnostic timelines. Background: Over the past two decades, the average time to ALS diagnosis in the U.S. has remained unchanged at 12 months. ALS patients see 3-4 clinicians prior to referral to an ALS specialist for diagnosis confirmation and/or treatment initiation. There is an urgent need to identify where delays occur, so that targeted clinician awareness may be raised about early suspicion and referrals. Methods: Review of Medicare claims database for health care utilization patterns by ALS beneficiaries during diagnostic journey. Survey of typical clinic wait times for new consultations reported by 75-78 ALS Certified Treatment Centers of Excellence (2019-2021). Results: During 2011-2021, 78,520 Medicare beneficiaries were diagnosed with ALS (T0). The mean (median) timelines between first neurologist ambulatory visit and T0, is 16.5 (11.0) months; mean ± SD for ALS/neuromuscular providers being 9.6 ± 12.6 months versus 16.7 ± 17.5 months for non-neuromuscular neurologists. During the 12-months preceding T0, an ALS patient undergoes median(max) 1.5(4.0) brain-MRIs, 1.6(6.0) spine-MRIs, and 1.3(4.0) electromyography studies. Greater than 75% of ALS centers consistently report ≤ 4 week wait times for new ALS consults. This study introduces "thinkALS," an easy-to-use clinical diagnostic and referral guide for non-ALS neurologists to tackle this challenge. Conclusions: This study is the first to provide metrics on how non-neuromuscular/ALS specialists contribute to ALS diagnostic timelines in the U.S.}, } @article {pmid39651269, year = {2024}, author = {O'Neill, K and Shaw, R and Bolger, I and , and Tam, O and Phatnani, H and Hammell, MG}, title = {ALS molecular subtypes are a combination of cellular, genetic, and pathological features learned by deep multiomics classifiers.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2024.07.19.603731}, pmid = {39651269}, issn = {2692-8205}, support = {R01 NS116350/NS/NINDS NIH HHS/United States ; R01 NS118183/NS/NINDS NIH HHS/United States ; R01 NS118570/NS/NINDS NIH HHS/United States ; RF1 NS118570/NS/NINDS NIH HHS/United States ; }, abstract = {Amyotrophic Lateral Sclerosis (ALS) is a complex syndrome with multiple genetic causes and wide variation in disease presentation. Despite this general heterogeneity, several common factors have been identified. For example, nearly all patients show pathological accumulations of phosphorylated TDP-43 protein in affected regions of the motor cortex and spinal cord. Moreover, large patient cohort studies have revealed that most patient samples can be grouped into a small number of ALS subtypes, as defined by their transcriptomic profiles. These ALS molecular subtypes can be grouped by whether postmortem motor cortex samples display signatures of: mitochondrial dysfunction and oxidative stress (ALS-Ox), microglial activation and neuroinflammation (ALS-Glia), or dense TDP-43 pathology and associated transposable element de-silencing (ALS-TE). In this study, we have built a deep layer ALS neural network classifier (DANcer) that has learned to accurately assign patient samples to these ALS subtypes, and which can be run on either bulk or single-cell datasets. Upon applying this classifier to an expanded ALS patient cohort from the NYGC ALS Consortium, we show that ALS Molecular Subtypes are robust across clinical centers, with no new subtypes appearing in a cohort that has quadrupled in size. Signatures from two of these molecular subtypes strongly correlate with disease duration: ALS-TE signatures in cortex and ALS-Glia signatures in spinal cord, revealing molecular correlates of clinical features. Finally, we use single nucleus RNA sequencing to reveal the cell type-specific contributions to ALS subtype, as determined by our single-cell classifier (scDANCer). Single-cell transcriptomes reveal that ALS molecular subtypes are recapitulated in neurons and glia, with both ALS-wide shared alterations in each cell type as well as ALS subtype-specific alterations. In summary, ALS molecular subtypes: (1) are robust across large cohorts of sporadic and familial ALS patient samples, (2) represent a combination of cellular, genetic, and pathological features, and (3) correlate with clinical features of ALS.}, } @article {pmid39651224, year = {2024}, author = {Kodavati, M and Maloji Rao, VH and Mitra, J and Hegde, ML}, title = {Selective Inhibition of Cytosolic PARylation via PARG99: A Targeted Approach for Mitigating FUS-associated Neurodegeneration.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2024.11.25.625276}, pmid = {39651224}, issn = {2692-8205}, abstract = {Neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) are characterized by complex etiologies, often involving disruptions in functions of RNA/DNA binding proteins (RDBPs) such as FUS and TDP-43. The cytosolic mislocalization and aggregation of these proteins are linked to accumulation of unresolved stress granules (SGs), which exacerbate the disease progression. Poly-ADP-ribose polymerase (PARP)-mediated PARylation plays a critical role in this pathological cascade, making it a potential target for intervention. However, conventional PARP inhibitors are limited by their detrimental effects on DNA repair pathways, which are already compromised in ALS. To address this limitation, we investigated a strategy focused on targeting the cytosolic compartment by expressing the cytosol-specific, natural PAR- glycohydrolase (PARG) isoform, PARG99. Using ALS patient derived FUS mutant induced pluripotent cells (iPSCs) and differentiated neurons, we observed elevated levels of FUS in insoluble fractions in mutant cells compared to mutation-corrected isogenic lines. The insoluble FUS as well as TDP-43 levels increased further in sodium arsenite-treated or oxidatively stressed cells, correlating with accumulation of unresolved SGs. Notably, both PARG99 and PARP inhibitors reduced SG formation and insoluble FUS levels, however, PARG99 treated cells exhibited significantly lower DNA damage markers and improved viability under oxidative and arsenite stress. This study highlights the potential of PARG99 as a cytosol-specific intervention to mitigate FUS-associated toxicity while preserving critical nuclear DNA repair mechanisms, offering a promising strategy for addressing the underlying pathology of ALS and potentially other SG-associated neurodegenerative diseases.}, } @article {pmid39651197, year = {2024}, author = {Grant, OA and Iacoangeli, A and Zwamborn, RAJ and van Rheenen, W and Byrne, R and Van Eijk, KR and Kenna, K and van Vugt, JJFA and Cooper-Knock, J and Kenna, B and Vural, A and Topp, S and Campos, Y and Weber, M and Smith, B and Dobson, R and van Es, MA and Vourc'h, P and Corcia, P and de Carvalho, M and Gotkine, M and Panades, MP and Mora, JS and Mill, J and Garton, F and McRae, A and Wray, NR and Shaw, PJ and Landers, JE and Glass, JD and Shaw, CE and Basak, N and Hardiman, O and Van Damme, P and McLaughlin, RL and van den Berg, LH and Veldink, JH and Al-Chalabi, A and Al Khleifat, A}, title = {Sex-specific DNA methylation differences in Amyotrophic lateral sclerosis.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2024.11.22.624866}, pmid = {39651197}, issn = {2692-8205}, abstract = {Sex is an important covariate in all genetic and epigenetic research due to its role in the incidence, progression and outcome of many phenotypic characteristics and human diseases. Amyotrophic lateral sclerosis (ALS) is a motor neuron disease with a sex bias towards higher incidence in males. Here, we report for the first time a blood-based epigenome-wide association study meta-analysis in 9274 individuals after stringent quality control (5529 males and 3975 females). We identified a total of 226 ALS saDMPs (sex-associated DMPs) annotated to a total of 159 unique genes. These ALS saDMPs were depleted at transposable elements yet significantly enriched at enhancers and slightly enriched at 3'UTRs. These ALS saDMPs were enriched for transcription factor motifs such as ESR1 and REST. Moreover, we identified an additional 10 genes associated with ALS saDMPs through chromatin loop interactions, suggesting a potential regulatory role for these saDMPs on distant genes. Furthermore, we investigated the relationship between DNA methylation at specific CpG sites and overall survival in ALS using Cox proportional hazards models. We identified two ALS saDMPs, cg14380013 and cg06729676, that showed significant associations with survival. Overall, our study reports a reliable catalogue of sex-associated ALS saDMPs in ALS and elucidates several characteristics of these sites using a large-scale dataset. This resource will benefit future studies aiming to investigate the role of sex in the incidence, progression and risk for ALS.}, } @article {pmid39651147, year = {2024}, author = {Fleming, AC and Rao, NR and Wright, M and Savas, JN and Kiskinis, E}, title = {The ALS-associated co-chaperone DNAJC7 mediates neuroprotection against proteotoxic stress by modulating HSF1 activity.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2024.12.01.626216}, pmid = {39651147}, issn = {2692-8205}, abstract = {The degeneration of neurons in patients with amyotrophic lateral sclerosis (ALS) is commonly associated with accumulation of misfolded, insoluble proteins. Heat shock proteins (HSPs) are central regulators of protein homeostasis as they fold newly synthesized proteins and refold damaged proteins. Heterozygous loss-of- function mutations in the DNAJC7 gene that encodes an HSP co-chaperone were recently identified as a cause for rare forms of ALS, yet the mechanisms underlying pathogenesis remain unclear. Using mass spectrometry, we found that the DNAJC7 interactome in human motor neurons (MNs) is enriched for RNA binding proteins (RBPs) and stress response chaperones. MNs generated from iPSCs with the ALS-associated mutation R156X in DNAJC7 exhibit increased insolubility of its client RBP HNRNPU and associated RNA metabolism alterations. Additionally, DNAJC7 haploinsufficiency renders MNs increasingly susceptible to proteotoxic stress and cell death as a result of an ablated HSF1 stress response pathway. Critically, expression of HSF1 in mutant DNAJC7 MNs is sufficient to rescue their sensitivity to proteotoxic stress, while postmortem ALS patient cortical neurons exhibit a reduction in the expression of HSF1 pathway genes. Taken together, our work identifies DNAJC7 as a crucial mediator of HNRNPU function and stress response pathways in human MNs and highlights HSF1 as a therapeutic target in ALS.}, } @article {pmid39650285, year = {2024}, author = {Hu, Y and Deeba, E and Kläppe, U and Öijerstedt, L and Andersson, J and Ruffin, N and Piehl, F and Ingre, C and Fang, F and Seitz, C}, title = {Immune cells and the trajectories of depression, anxiety, and cognitive function among people with amyotrophic lateral sclerosis.}, journal = {Brain, behavior, & immunity - health}, volume = {42}, number = {}, pages = {100907}, pmid = {39650285}, issn = {2666-3546}, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) represents a complex syndrome characterized by motor, psychiatric, and cognitive symptoms, where associations between cellular immune features and non-motor manifestations remain unknown.

METHODS: In this cohort study, we enrolled 250 incident people with ALS (pwALS) assessed with the Hospital Anxiety and Depression Scale, and 226 pwALS with the Montreal Cognitive Assessment, including 218 overlapping pwALS. All individuals were diagnosed between January 2015 and January 2023 in Stockholm, Sweden. We applied joint latent class models to delineate distinct trajectories of anxiety, depression, and cognition, incorporating survival outcomes. A majority of the pwALS had data on leukocyte counts and flow cytometric analyses using a comprehensive T cell panel. We then used immune cell subtypes measured at diagnosis to predict trajectories of these outcomes following ALS diagnosis.

RESULTS: We identified two distinct trajectories for anxiety, depression, and cognitive function following ALS diagnosis. PwALS with longer survival displayed more stable trajectories, while those with shorter survival showed decreasing anxiety symptom, increasing depressive symptom, and declining cognitive function. Higher count of leukocytes at the time of ALS diagnosis tended to associate with anxiety and depression trajectories related to shorter survival. Among T cell subpopulations, several CD8[+] T cell subsets were associated with a stable trajectory of depressive symptom, and, in turn, better survival.

CONCLUSION: ALS-associated psychiatric and cognitive trajectories vary significantly between pwALS with different prognosis. Certain T cell subsets measured at diagnosis might be indicative of depression trajectories post-diagnosis.}, } @article {pmid39649550, year = {2024}, author = {Han, S and Li, RH and Gao, P}, title = {Gut microbiota participates and remodels host metabolism: From treating patients to treating their gut flora.}, journal = {World journal of gastroenterology}, volume = {30}, number = {45}, pages = {4839-4843}, pmid = {39649550}, issn = {2219-2840}, mesh = {Humans ; *Gastrointestinal Microbiome ; Animals ; Uric Acid/blood/metabolism ; Hyperuricemia/microbiology/drug therapy/blood/metabolism ; Metabolomics/methods ; Feces/microbiology ; }, abstract = {In this editorial, we comment on Liu et al's article published in the recent issue of the World Journal of Gastroenterology. Biochemically and pathologically, Liu et al proved that the urate-lowering activity of leech total protein (LTP) was mainly attributed to the rectification of gut microbiota. Specifically, we noticed the change in Bacteroides and Akkermansia after LTP administration. Both bacteria have been reported to alleviate metabolic dysfunction-associated steatohepatitis and other chronic metabolic diseases. LTP was administrated through intragastric manners. Most possibly, LTP would be digested by the gut microbiota further. The anti-hyperuricemia effects should, to the most possible extent, be exerted by the peptides or their secondary metabolic products. Human gut microbiota communicates with other organs through metabolites generated by the microbes or co-metabolized with the host. Whether the anti-hyperuricemia effect could be partially ascribed to the microbiota metabolites also deserves to be discussed. Although metabolomics analysis was performed for serum samples, fecal metabolomics was highly advocated which could facilitate exact mechanism explanation. This study implied that gut microbiota contains many unexplored targets with different therapeutic potentials. It is foreseeable that utilizing these targets can avoid the impairment or side effects of directly using human targets to some extent.}, } @article {pmid39649175, year = {2024}, author = {Harvey, C and Nowak, A and Zhang, S and Moll, T and Weimer, AK and Barcons, AM and Dos Santos Souza, C and Ferraiuolo, L and Kenna, K and Zaitlen, N and Caggiano, C and Shaw, PJ and Snyder, MP and Mill, J and Hannon, E and Cooper-Knock, J}, title = {Evaluation of a biomarker for amyotrophic lateral sclerosis derived from a hypomethylated DNA signature of human motor neurons.}, journal = {Research square}, volume = {}, number = {}, pages = {}, pmid = {39649175}, issn = {2693-5015}, support = {R01 HL101388/HL/NHLBI NIH HHS/United States ; P50 HL083800/HL/NHLBI NIH HHS/United States ; P30 DK116074/DK/NIDDK NIH HHS/United States ; R01 HL122939/HL/NHLBI NIH HHS/United States ; UM1 HG009442/HG/NHGRI NIH HHS/United States ; /WT_/Wellcome Trust/United Kingdom ; }, abstract = {Amyotrophic lateral sclerosis (ALS) lacks a specific biomarker, but is defined by relatively selective toxicity to motor neurons (MN). As others have highlighted, this offers an opportunity to develop a sensitive and specific biomarker based on detection of DNA released from dying MN within accessible biofluids. Here we have performed whole genome bisulfite sequencing (WGBS) of iPSC-derived MN from neurologically normal individuals. By comparing MN methylation with an atlas of tissue methylation we have derived a MN-specific signature of hypomethylated genomic regions, which accords with genes important for MN function. Through simulation we have optimised the selection of regions for biomarker detection in plasma and CSF cell-free DNA (cfDNA). However, we show that MN-derived DNA is not detectable via WGBS in plasma cfDNA. In support of our experimental finding, we show theoretically that the relative sparsity of lower MN sets a limit on the proportion of plasma cfDNA derived from MN which is below the threshold for detection of WGBS. Our findings are important for the ongoing development of ALS biomarkers. The MN-specific hypomethylated genomic regions we have derived could be usefully combined with more sensitive detection methods and perhaps with study of CSF instead of plasma. Indeed we demonstrate that neuronal-derived DNA is detectable in CSF. Our work is relevant for all diseases featuring death of rare cell-types.}, } @article {pmid39647703, year = {2025}, author = {Watters, JJ and Bell, MC and Que, SKT}, title = {Regarding response to Watters et al's "Educational intervention targeting primary care residents improves skin cancer recognition in patients with skin of color".}, journal = {Journal of the American Academy of Dermatology}, volume = {92}, number = {4}, pages = {e105-e106}, doi = {10.1016/j.jaad.2024.11.051}, pmid = {39647703}, issn = {1097-6787}, } @article {pmid39645528, year = {2024}, author = {Ríos-López, AL and Garza-Velásquez, MF and González, GM and Becerril-García, MA and Flores-Maldonado, O}, title = {Prevalence, virulence factors and antifungal susceptibility of oral isolates of Candida albicans from patients with cystic fibrosis in Mexico.}, journal = {Revista iberoamericana de micologia}, volume = {41}, number = {2-3}, pages = {31-36}, doi = {10.1016/j.riam.2024.09.001}, pmid = {39645528}, issn = {2173-9188}, mesh = {Humans ; *Cystic Fibrosis/microbiology/complications ; *Virulence Factors/genetics ; *Candida albicans/drug effects/isolation & purification/genetics ; Mexico/epidemiology ; *Antifungal Agents/pharmacology ; *Microbial Sensitivity Tests ; Female ; Male ; Adult ; Young Adult ; Adolescent ; *Candidiasis, Oral/microbiology/epidemiology ; Prevalence ; Child ; Drug Resistance, Fungal ; Biofilms/growth & development ; Mouth/microbiology ; Child, Preschool ; }, abstract = {BACKGROUND: Candida species are frequently isolated from the oral cavity of patients with cystic fibrosis. However, the information on the role of Candida in cystic fibrosis is scarce.

AIMS: This study aimed to evaluate the prevalence, virulence profile and antifungal susceptibility of oral isolates of Candida albicans recovered from patients with cystic fibrosis.

METHODS: Oropharyngeal swab samples were collected from sixty-five cystic fibrosis patients and sixty-five healthy individuals. Candida isolates were identified by MALDI-TOF VITEK-MS. Proteinase, phospholipase and esterase activity, biofilm production and level expression of ALS, SAP and PLB genes in C. albicans were evaluated. Minimal inhibitory concentration values were determined by means of an antifungal susceptibility test.

RESULTS: Oral Candida colonization in cystic fibrosis patients was 66.15%, while in healthy individuals was 36.92%. C. albicans was the most frequently isolated species. C. albicans strains from cystic fibrosis patients were high producers of protease and biofilm, and had higher expression levels of adhesin and protease-associated genes in comparison with healthy subjects. Among the C. albicans strains isolated from cystic fibrosis patients, 18.91% were resistant to itraconazole, while 16.21% exhibited resistance to ketoconazole and fluconazole, and only one strain was resistant to voriconazole.

CONCLUSIONS: This work represents a surveillance study on virulence patterns and antifungal susceptibility of Candida from the oropharyngeal tract in cystic fibrosis.}, } @article {pmid39645221, year = {2025}, author = {Bajpai, A and Bharathi, V and Patel, BK}, title = {Therapeutic targeting of the oxidative stress generated by pathological molecular pathways in the neurodegenerative diseases, ALS and Huntington's.}, journal = {European journal of pharmacology}, volume = {987}, number = {}, pages = {177187}, doi = {10.1016/j.ejphar.2024.177187}, pmid = {39645221}, issn = {1879-0712}, mesh = {Animals ; Humans ; *Amyotrophic Lateral Sclerosis/metabolism/drug therapy/pathology/genetics ; *Antioxidants/pharmacology/therapeutic use ; *Huntington Disease/metabolism/drug therapy/pathology/genetics ; Molecular Targeted Therapy/methods ; Neurodegenerative Diseases/metabolism/drug therapy/pathology ; *Oxidative Stress/drug effects ; }, abstract = {Neurodegenerative disorders are characterized by a progressive decline of specific neuronal populations in the brain and spinal cord, typically containing aggregates of one or more proteins. They can result in behavioral alterations, memory loss and a decline in cognitive and motor abilities. Various pathways and mechanisms have been outlined for the potential treatment of these diseases, where redox regulation is considered as one of the most common druggable targets. For example, in amyotrophic lateral sclerosis (ALS) with superoxide dismutase-1 (SOD1) pathology, there is a downregulation of the antioxidant response nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. TDP-43 proteinopathy in ALS is associated with elevated levels of reactive oxygen species and mitochondrial dyshomeostasis. In ALS with mutant FUS, poly ADP ribose polymerase-dependent X ray repair cross complementing 1/DNA-ligase recruitment to the sites of oxidative DNA damage is affected, thereby causing defects in DNA damage repair. Oxidative stress in Huntington's disease (HD) with mutant huntingtin accumulation manifests as protein oxidation, metabolic energetics dysfunction, metal ion dyshomeostasis, DNA damage and mitochondrial dysfunction. The impact of oxidative stress in the progression of these diseases further warrants studies into the role of antioxidants in their treatment. While an antioxidant, edaravone, has been approved for therapeutics of ALS, numerous antioxidant molecules failed to pass the clinical trials despite promising initial studies. In this review, we summarize the oxidative stress pathways and redox modulators that are investigated in ALS and HD using various models.}, } @article {pmid39645085, year = {2025}, author = {Ediriweera, GR and Sivaram, AJ and Cowin, G and Brown, ML and McAlary, L and Lum, JS and Fletcher, NL and Robinson, L and Simpson, JD and Chen, L and Wasielewska, JM and Byrne, E and Finnie, JW and Manavis, J and White, AR and Yerbury, JJ and Thurecht, KJ and Vine, KL}, title = {Lipid nanoparticles and transcranial focused ultrasound enhance the delivery of SOD1 antisense oligonucleotides to the murine brain for ALS therapy.}, journal = {Journal of controlled release : official journal of the Controlled Release Society}, volume = {378}, number = {}, pages = {221-235}, doi = {10.1016/j.jconrel.2024.11.074}, pmid = {39645085}, issn = {1873-4995}, mesh = {Animals ; *Oligonucleotides, Antisense/administration & dosage/pharmacokinetics ; *Amyotrophic Lateral Sclerosis/therapy/drug therapy/genetics ; *Superoxide Dismutase-1/genetics ; Mice, Inbred C57BL ; *Nanoparticles/administration & dosage/chemistry ; *Brain/metabolism ; Mice, Transgenic ; Lipids/chemistry/administration & dosage ; Mice ; Microbubbles ; Spinal Cord/metabolism ; Male ; Blood-Brain Barrier/metabolism ; Liposomes ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease with extremely limited therapeutic options. One key pathological feature of ALS is the abnormal accumulation of misfolded proteins within motor neurons. Hence, reducing the burden of misfolded protein has emerged as a promising therapeutic approach. Antisense oligonucleotides (ASOs) have the potential to effectively silence proteins with gain-of-function mutations, such as superoxide dismutase 1 (SOD1). However, ASO delivery to the central nervous system (CNS) is hindered by poor blood-brain barrier (BBB) penetration and the invasiveness of intrathecal administration. In the current study, we demonstrate effective systemic delivery of a next-generation SOD1 ASO (Tofersen) into the brain of wildtype and G93A-SOD1 transgenic C57BL/6 mice using calcium phosphate lipid nanoparticles (CaP lipid NPs). We show that transcranial focused ultrasound (FUS) with intravenously administered microbubbles can significantly enhance ASO-loaded nanoparticle delivery into the mouse brain. Magnetic resonance imaging (MRI) and immunohistological analysis showed reduced SOD1 expression in the FUS-exposed brain regions and increased motor neuron count in the spinal cord of treated mice suggesting decreased motor neuron degeneration. Importantly, the BBB opening was transient without evidence of structural changes, neuroinflammation or damage to the brain tissue, indicating that the treatment is well tolerated. Overall, our results highlight FUS-assisted nanoparticle delivery of ASOs as a promising non-invasive therapeutic strategy for the treatment of ALS and CNS diseases more broadly.}, } @article {pmid39645043, year = {2025}, author = {Needle, C and Brinks, A and Shapiro, J and Lo Sicco, K}, title = {Response to Chen et al's "Emergence of Janus kinase inhibitors led to increase in proportion of severe alopecia areata patients receiving treatment: A retrospective cohort study".}, journal = {Journal of the American Academy of Dermatology}, volume = {92}, number = {4}, pages = {e119-e120}, doi = {10.1016/j.jaad.2024.10.118}, pmid = {39645043}, issn = {1097-6787}, } @article {pmid39644980, year = {2025}, author = {Guerra San Juan, I and Brunner, JW and Eggan, K and Toonen, RF and Verhage, M}, title = {KIF5A regulates axonal repair and time-dependent axonal transport of SFPQ granules and mitochondria in human motor neurons.}, journal = {Neurobiology of disease}, volume = {204}, number = {}, pages = {106759}, doi = {10.1016/j.nbd.2024.106759}, pmid = {39644980}, issn = {1095-953X}, mesh = {*Kinesins/metabolism/genetics ; *Axonal Transport/physiology ; Humans ; *Mitochondria/metabolism ; *Motor Neurons/metabolism ; *Axons/metabolism ; PTB-Associated Splicing Factor/metabolism ; Nerve Regeneration/physiology ; Cells, Cultured ; Neuronal Outgrowth/physiology ; }, abstract = {Mutations in the microtubule-binding motor protein kinesin 5 A (KIF5A) are implicated in several adult-onset motor neuron diseases, including Amyotrophic Lateral Sclerosis, Spastic Paraplegia Type 10 and Charcot-Marie-Tooth Disease Type 2. While KIF5 family members transport a variety of cargos along axons, the specific cargos affected by KIF5A mutations remain poorly understood. Here, we generated KIF5Anull mutant human motor neurons and analyzed the impact on axonal transport and motor neuron outgrowth and regeneration in vitro. KIF5A deficiency caused reduced neurite complexity in young neurons (DIV14) and defects in axonal regeneration. KIF5A deficiency did not affect neurofilament transport but impaired mitochondrial motility and anterograde speed at DIV42. Notably, KIF5A deficiency strongly reduced anterograde transport of splicing factor proline/glutamine-rich (SFPQ)-associated RNA granules in DIV42 axons. Hence, KIF5A plays a critical role in promoting axonal regrowth after injury and in driving the anterograde transport of mitochondria and especially SFPQ-associated RNA granules in mature neurons.}, } @article {pmid39644798, year = {2025}, author = {Toko, M and Ohshita, T and Nakamori, M and Ueno, H and Akiyama, Y and Maruyama, H}, title = {Myelin measurement in amyotrophic lateral sclerosis with synthetic MRI: A potential diagnostic and predictive method.}, journal = {Journal of the neurological sciences}, volume = {468}, number = {}, pages = {123337}, doi = {10.1016/j.jns.2024.123337}, pmid = {39644798}, issn = {1878-5883}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnostic imaging/pathology ; Male ; Female ; Middle Aged ; *Magnetic Resonance Imaging/methods ; *Myelin Sheath/pathology ; Aged ; Adult ; Predictive Value of Tests ; *Brain/diagnostic imaging ; }, abstract = {BACKGROUND: Myelin damage has recently been highlighted as a major causative factor of amyotrophic lateral sclerosis (ALS). Although myelin damage has been pathologically identified in ALS, it has not been clinically evaluated. This study aimed to quantify myelin volume using synthetic MRI to evaluate myelin damage in patients with ALS, and determine its association with clinical parameters.

METHODS: We evaluated patients with ALS (n = 35) and individuals (n = 16) without intracranial disease using synthetic magnetic resonance imaging (MRI) and measured total myelin volume (TMV), myelin fraction (MYF), and myelin partial volume (VMY) in the cerebral peduncle and the posterior limb of the internal capsule (PLIC). We also investigated factors associated with acquired quantitative values.

RESULTS: The TMV was significantly lower in the patients with ALS than in the control group (P = 0.045). The TMV (r = 0.42, P = 0.013) and MYF (r = 0.34, P = 0.047) significantly correlated with Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) scores in the patients, and MYF was independent of the traditional white matter lesion grading score. The VMY of the PLIC was significantly lower in the ALS than the control group (P = 0.018), and the ALS group significantly correlated with ALSFRS-R scores (r = 0.36, P = 0.033).

CONCLUSIONS: Myelin damage can be quantified by synthetic MRI as reduced myelin volume, with the possibility of predicting prognoses in patients with ALS. Furthermore, myelin measurements in the PLIC might be a novel diagnostic marker for ALS.}, } @article {pmid39643934, year = {2025}, author = {Farrokhzad, R and Seyedalipour, B and Baziyar, P and Hosseinkhani, S}, title = {Insight Into Factors Influencing the Aggregation Process in Wild-Type and P66R Mutant SOD1: Computational and Spectroscopic Approaches.}, journal = {Proteins}, volume = {93}, number = {4}, pages = {885-907}, doi = {10.1002/prot.26765}, pmid = {39643934}, issn = {1097-0134}, mesh = {*Superoxide Dismutase-1/chemistry/genetics/metabolism ; Humans ; Molecular Dynamics Simulation ; Protein Aggregates ; Hydrophobic and Hydrophilic Interactions ; Mutation ; *Amyotrophic Lateral Sclerosis/genetics/metabolism ; Protein Folding ; Spectroscopy, Fourier Transform Infrared ; Amyloid/chemistry/metabolism ; Protein Conformation, beta-Strand ; Recombinant Proteins/chemistry/genetics/metabolism ; }, abstract = {Disturbances in metal ion homeostasis associated with amyotrophic lateral sclerosis (ALS) have been described for several years, but the exact mechanism of involvement is not well understood. To elucidate the role of metalation in superoxide dismutase (SOD1) misfolding and aggregation, we comprehensively characterized the structural features (apo/holo forms) of WT-SOD1 and P66R mutant in loop IV. Using computational and experimental methodologies, we assessed the physicochemical properties of these variants and their correlation with protein aggregation at the molecular level. Modifications in apo-SOD1 compared to holo-SOD1 were more pronounced in flexibility, stability, hydrophobicity, and intramolecular interactions, as indicated by molecular dynamics simulations. The enzymatic activities of holo/apo-WT SOD1 were 1.30 and 1.88-fold of the holo/apo P66R mutant, respectively. Under amyloid-inducing conditions, decreased ANS fluorescence intensity in the apo-form relative to the holo-form suggested pre-fibrillar species and amyloid aggregate growth due to occluded hydrophobic pockets. FTIR spectroscopy revealed that apo-WT-SOD1 and apo-P66R exhibited a mixture of parallel and intermolecular β-sheet structures, indicative of aggregation propensity. Aggregate species were identified using TEM, Congo red staining, and ThT/ANS fluorescence spectroscopy. Thermodynamic analyses with GdnHCl demonstrated that metal deficit, mutation, and intramolecular disulfide bond reduction are essential for initiating SOD1 misfolding and aggregation. These disruptions destabilize the dimer-monomer equilibrium, promoting dimer dissociation into monomers and decreasing the thermodynamic stability of SOD1 variants, thus facilitating amyloid/amorphous aggregate formation. Our findings offer novel insights into protein aggregation mechanisms in disease pathology and highlight potential therapeutic strategies against toxic protein aggregation, including SOD1.}, } @article {pmid39643926, year = {2025}, author = {Wang, J and Du, Y and Zhang, L and Deng, Y and Wang, T and Wang, S and Ji, M}, title = {Pro-197-Ser mutation combinations in acetolactate synthase (ALS) homoeologous genes affect ALS inhibitor herbicide resistance levels in Monochoria korsakowii.}, journal = {Pest management science}, volume = {81}, number = {4}, pages = {1894-1902}, doi = {10.1002/ps.8586}, pmid = {39643926}, issn = {1526-4998}, support = {32372594//National Natural Science Foundation of China/ ; }, mesh = {*Acetolactate Synthase/genetics/antagonists & inhibitors/metabolism ; *Herbicide Resistance/genetics ; *Herbicides/pharmacology ; *Plant Proteins/genetics/metabolism/antagonists & inhibitors ; Mutation ; Sulfonylurea Compounds/pharmacology ; *Poaceae/genetics/drug effects/enzymology ; Nicotinic Acids/pharmacology ; Sulfonamides ; Uridine/analogs & derivatives ; }, abstract = {BACKGROUND: Monochoria korsakowii is a common broadleaf weed found in rice (Oryza sativa) fields. Acetolactate synthase (ALS) inhibitor herbicides are commonly used to control broadleaf weeds in rice fields. However, prolonged herbicide use has exacerbated resistance issues. In this study, we evaluated the resistance to ALS inhibitors in populations where the same mutation occurred separately and simultaneously in the two ALS homoeologous genes (ALS1 and ALS2) and investigated the resistance mechanisms in M. korsakowii.

RESULTS: Monochoria korsakowii exhibited high resistance to bensulfuron-methyl, low resistance to penoxsulam, and sensitivity to imazethapyr. Three resistant populations were identified: M-1 and M-2, which independently evolved the Pro-197-Ser mutation in ALS1 and ALS2, respectively, and M-3, which harbored this mutation in both ALS1 and ALS2. The sensitivity of ALS isolated from these populations to herbicide inhibition corresponded to the whole-plant resistance levels. Subsequently, we cloned and transformed Pro-197-Ser-mutated ALS1 and ALS2 into Arabidopsis thaliana. The resistance of homozygous A. thaliana to bensulfuron-methyl and penoxsulam aligned with bioassay trends. Furthermore, we measured the ploidy, relative expression, and copy number of ALS1 and ALS2, and found no significant differences, suggesting that the evolution of resistance was primarily attributed to the Pro-197-Ser mutation. Finally, we developed a derived cleaved amplified polymorphic sequence marker for detecting Pro-197-Ser mutation in ALS.

CONCLUSION: The same mutation occurring separately in homoeologous genes resulted in similar resistance levels, whereas simultaneous mutations in homoeologous genes led to increased resistance levels. © 2024 Society of Chemical Industry.}, } @article {pmid39642451, year = {2025}, author = {He, X}, title = {Hyperspectral Raman imaging with multivariate curve resolution-alternating least square (MCR-ALS) analysis for xylazine-containing drug mixtures.}, journal = {Forensic science international}, volume = {367}, number = {}, pages = {112314}, doi = {10.1016/j.forsciint.2024.112314}, pmid = {39642451}, issn = {1872-6283}, mesh = {*Xylazine/analysis/chemistry ; *Spectrum Analysis, Raman/methods ; Least-Squares Analysis ; Humans ; Mannitol/chemistry ; Acetaminophen/chemistry ; *Hyperspectral Imaging ; Multivariate Analysis ; Excipients/chemistry ; }, abstract = {Xylazine, increasingly implicated in illicit opioid overdose deaths, poses a significant public health threat due to its synergistic effects with fentanyl and resistance to naloxone reversal. Despite its rising prevalence, xylazine is not classified as a controlled substance, leading to its exclusion from routine forensic screening. This study introduces a novel analytical method combining Raman hyperspectral imaging with Multivariate Curve Resolution-Alternating Least Squares (MCR-ALS) to detect xylazine in drug mixtures containing common excipients such as acetaminophen, dipyrone, and mannitol. Utilizing only non-negativity constraints, MCR-ALS successfully resolved the Raman spectrum of xylazine at levels as low as 5 % without reference spectra. The method demonstrated robust performance, with percent variance explained (R[2]) values of 99.60 %, 99.80 %, and 99.91 % for the drug mixtures containing 25 %, 10 %, and 5 % xylazine, respectively.}, } @article {pmid39641862, year = {2024}, author = {Zhang, J and Zhang, X and Xiao, B and Ouyang, J and Wang, P and Peng, X}, title = {Mendelian randomization study of causal link from Cerebrospinal fluid metabolomics to neurodegenerative diseases.}, journal = {Neurogenetics}, volume = {26}, number = {1}, pages = {15}, pmid = {39641862}, issn = {1364-6753}, support = {No. YZ2020MS04//President Foundation of The Fifth Affiliated Hospital, Southern Medical University/ ; }, mesh = {Humans ; *Mendelian Randomization Analysis ; *Genome-Wide Association Study ; *Neurodegenerative Diseases/genetics/cerebrospinal fluid ; *Metabolomics/methods ; *Amyotrophic Lateral Sclerosis/genetics/cerebrospinal fluid ; Multiple Sclerosis/genetics/cerebrospinal fluid ; Alzheimer Disease/genetics/cerebrospinal fluid ; Parkinson Disease/genetics/cerebrospinal fluid ; Polymorphism, Single Nucleotide ; }, abstract = {To investigate the causal relationships between cerebrospinal fluid (CSF) metabolites and various neurodegenerative diseases (NDDs), we conducted a two-sample Mendelian randomization (MR) analysis. This study utilized summary statistics from genome-wide association studies (GWAS) of CSF metabolites and four common neurodegenerative diseases: Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS). MR methods were employed to determine causal associations, with the inverse variance weighted method as the primary approach. Additionally, different GWAS summary data for NDDs were used to validate the initial results and perform sensitivity analyses to enhance the robustness of the findings. Finally, reverse MR analyses were conducted to assess the possibility of reverse causation. Combining results from the initial and replication phases of MR analysis, we identified potential causal relationships between various CSF metabolites and different NDDs. Specifically, we found potential causal relationships between five CSF metabolites and AD, six CSF metabolites and MS, and thirteen CSF metabolites and ALS. Further sensitivity analyses confirmed the robustness of these associations. Reverse MR analysis indicated causal effects of AD on glucuronate and ALS on acetylcarnitine (C2). Our study, through genetic means, demonstrates close causal associations between the specific types of CSF metabolites and the risk of NDDS (AD, PD, MS, and ALS), providing useful guidance for future clinical researches.}, } @article {pmid39641521, year = {2025}, author = {Manera, U and Callegaro, S and Canosa, A and Palumbo, F and Grassano, M and Bombaci, A and Dagliati, A and Bosoni, P and Daviddi, M and Casale, F and Cabras, S and Matteoni, E and De Marchi, F and Mazzini, L and Moglia, C and Vasta, R and Calvo, A and Chiò, A}, title = {Croplands proximity is associated with amyotrophic lateral sclerosis incidence and age at onset.}, journal = {European journal of neurology}, volume = {32}, number = {1}, pages = {e16464}, pmid = {39641521}, issn = {1468-1331}, support = {//Dipartimenti di Eccellenza/ ; //EU Joint Programme - Neurodegenerative Disease Research/ ; 259867//Seventh Framework Programme/ ; 2017SNW5MB//Ministero dell'Università e della Ricerca/ ; RF-2016-02362405//Ministero della Salute/ ; GA101017598//Horizon 2020 Framework Programme/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/epidemiology ; Humans ; Incidence ; *Age of Onset ; Female ; Male ; Middle Aged ; Aged ; *Crops, Agricultural ; Adult ; Registries ; Italy/epidemiology ; Risk Factors ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease resulting from an intricate interplay between genetics and environmental factors. Many studies have explored living in rural areas as a possible risk factor for ALS, without focusing simultaneously on incidence, age at onset and phenotypic features.

OBJECTIVE: To evaluate the effect of croplands residential proximity on ALS incidence and phenotype, focusing on age of onset, site of onset and progression rate.

METHODS: The address history of ALS patients belonging to the population-based Piemonte and Valle d'Aosta registry (PARALS), diagnosed between 2007 and 2014, was obtained for the 20 years prior to the onset date. The smoothed ALS incidence per year (im) was compared with the percentage of area covered by each crop for each municipality. A proximity score was calculated for each cropland by geolocation, measuring the percentage of area surrounding patients' residence for variable radii, and was used to compare croplands exposure and phenotype.

RESULTS: We observed an increased ALS incidence in the municipalities with a higher percentage of area covered by arable crops (R = 0.191, p < 0.001). Age at onset was significantly lower in those patients who lived near arable crops, with a median anticipation ranging from 1.8 to 3.4 years; using historical data, a significant anticipation was found also for patients living near vineyards.

DISCUSSION: Our study proved a direct association between arable crops and ALS risk and an inverse association between arable crops and vineyards proximity and age at onset, suggesting the possible causative role of specific environmental contaminants.}, } @article {pmid39640847, year = {2024}, author = {Raineri, D and De Marchi, F and Vilardo, B and Barbero Mazzucca, C and Scotti, L and Kustrimovic, N and Mazzini, L and Cappellano, G and Chiocchetti, A}, title = {Circulating GLAST[+] EVs are increased in amyotrophic lateral sclerosis.}, journal = {Frontiers in molecular biosciences}, volume = {11}, number = {}, pages = {1507498}, pmid = {39640847}, issn = {2296-889X}, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder, hallmarked by the gradual deterioration of motor neurons, culminating in muscle weakness and fatal paralysis. The exact etiology of ALS remains elusive, and there is a critical need for reliable biomarkers to aid in diagnosis and monitoring of disease progression. Extracellular vesicles (EVs) have emerged as promising candidates for biomarker discovery in neurodegenerative diseases such as ALS, giving access to pathologically relevant tissues otherwise typically challenging or invasive to sample. Indeed, EVs can derive by many cell types within the central nervous system, cross the blood-brain barrier and reach the blood, where they can be easily measured. One of the central mechanisms implicated in ALS pathology is glutamate excitotoxicity, which involves excessive glutamate accumulation due to impaired uptake by astrocytes and other glial cells, leading to neuronal damage. GLAST is a key glutamate transporter responsible for maintaining extracellular gluta-mate levels, and its dysregulation is thought to contribute significantly to ALS development and associated neuropathogenesis. Here, we applied a quick and validated method, to evaluate GLAST[+] EVs in ALS patients' plasma and age-matched healthy controls. We found an increase in GLAST[+] EVs that holds promise for uncovering novel diagnostic and therapeutic avenues in ALS research.}, } @article {pmid39640633, year = {2024}, author = {Nikafshan Rad, H and Su, Z and Trinh, A and Hakim Newton, MA and Shamsani, J and Nygc Als Consortium, and Karim, A and Sattar, A}, title = {Amyotrophic lateral sclerosis diagnosis using machine learning and multi-omic data integration.}, journal = {Heliyon}, volume = {10}, number = {20}, pages = {e38583}, pmid = {39640633}, issn = {2405-8440}, abstract = {Amyotrophic Lateral Sclerosis (ALS) is a complex and rare neurodegenerative disorder characterized by significant genetic, molecular, and clinical heterogeneity. Despite numerous endeavors to discover the genetic factors underlying ALS, a significant number of these factors remain unknown. This knowledge gap highlights the necessity for personalized medicine approaches that can provide more comprehensive information for the purposes of diagnosis, prognosis, and treatment of ALS. This work utilizes an innovative approach by employing a machine learning-facilitated, multi-omic model to develop a more comprehensive knowledge of ALS. Through unsupervised clustering on gene expression profiles, 9,847 genes associated with ALS pathways are isolated and integrated with 7,699 genes containing rare, presumed pathogenic genomic variants, leading to a comprehensive amalgamation of 17,546 genes. Subsequently, a Variational Autoencoder is applied to distil complex biomedical information from these genes, culminating in the creation of the proposed Multi-Omics for ALS (MOALS) model, which has been designed to expose intricate genotype-phenotype interconnections within the dataset. Our meticulous investigation elucidates several pivotal ALS signaling pathways and demonstrates that MOALS is a superior model, outclassing other machine learning models based on single omic approaches such as SNV and RNA expression, enhancing accuracy by 1.7 percent and 6.2 percent, respectively. The findings of this study suggest that analyzing the relationships within biological systems can provide heuristic insights into the biological mechanisms that help to make highly accurate ALS diagnosis tools and achieve more interpretable results.}, } @article {pmid39639468, year = {2024}, author = {Arango-Cortes, ML and Giraldo-Cadavid, LF and Latorre Quintana, M and Forero-Cubides, JD and Gonzalez-Bermejo, J}, title = {Diaphragm pacing compared with mechanical ventilation in patients with chronic respiratory failure caused by diaphragmatic dysfunction: a systematic review and meta-analysis.}, journal = {Expert review of respiratory medicine}, volume = {18}, number = {12}, pages = {1101-1111}, doi = {10.1080/17476348.2024.2421846}, pmid = {39639468}, issn = {1747-6356}, mesh = {Humans ; Chronic Disease/therapy ; *Diaphragm/physiopathology ; *Electric Stimulation Therapy/methods/statistics & numerical data ; Length of Stay/statistics & numerical data ; Quality of Life ; *Respiration, Artificial/adverse effects/methods/statistics & numerical data ; *Respiratory Paralysis/etiology/mortality/physiopathology/therapy ; Spinal Cord Injuries/complications/mortality/physiopathology/therapy ; Treatment Outcome ; }, abstract = {BACKGROUND: The effectiveness of diaphragmatic electrical stimulation (DES) compared to mechanical ventilation (MV) in improving clinical outcomes such as quality-of-life (QOL) and hospital stay remains inconsistent.

METHODS: We conducted a systematic review and meta-analysis by searching PubMed, Scopus, Google Scholar, LILACS, and IEEE Xplore. We included comparative studies (randomized controlled trials and observational studies) of DES administered via the phrenic nerve or intramuscular electrodes, compared with MV in adults with diaphragmatic paralysis or paresis. Two authors independently extracted data and assessed bias, with discrepancies resolved by a senior author. Results were pooled using the inverse variance method.

RESULTS: Out of 1,290 articles, nine were included in the systematic review, totaling 852 subjects. In spinal cord injury (SCI), one study reported lower mortality with DES, while three found no difference compared to MV. In these patients, DES was associated with shorter hospital stay, similar QOL, and heterogeneous results on respiratory infections. In amyotrophic lateral sclerosis (ALS), DES was associated with higher mortality and similar QOL compared to MV. Most SCI studies had a serious risk of bias.

CONCLUSION: DES shows potential in reducing hospital stay and respiratory infections in SCI but is associated with higher mortality in ALS.}, } @article {pmid39638345, year = {2025}, author = {Webster, CP and Hall, B and Crossley, OM and Dauletalina, D and King, M and Lin, YH and Castelli, LM and Yang, ZL and Coldicott, I and Kyrgiou-Balli, E and Higginbottom, A and Ferraiuolo, L and De Vos, KJ and Hautbergue, GM and Shaw, PJ and West, RJ and Azzouz, M}, title = {RuvBL1/2 reduce toxic dipeptide repeat protein burden in multiple models of C9orf72-ALS/FTD.}, journal = {Life science alliance}, volume = {8}, number = {2}, pages = {}, pmid = {39638345}, issn = {2575-1077}, support = {MR/V000470/1/MRC_/Medical Research Council/United Kingdom ; MR/V030140/1/MRC_/Medical Research Council/United Kingdom ; MR/W00416X/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Animals ; *C9orf72 Protein/genetics/metabolism ; *Amyotrophic Lateral Sclerosis/genetics/metabolism ; *Frontotemporal Dementia/genetics/metabolism ; Humans ; Mice ; *Disease Models, Animal ; *Dipeptides/metabolism ; *ATPases Associated with Diverse Cellular Activities/metabolism/genetics ; *DNA Helicases/genetics/metabolism ; *Mice, Transgenic ; DNA Repeat Expansion/genetics ; Carrier Proteins/metabolism/genetics ; Motor Neurons/metabolism ; Induced Pluripotent Stem Cells/metabolism ; Male ; }, abstract = {A G4C2 hexanucleotide repeat expansion in C9orf72 is the most common cause of amyotrophic lateral sclerosis and frontotemporal dementia (C9ALS/FTD). Bidirectional transcription and subsequent repeat-associated non-AUG (RAN) translation of sense and antisense transcripts leads to the formation of five dipeptide repeat (DPR) proteins. These DPRs are toxic in a wide range of cell and animal models. Therefore, decreasing RAN-DPRs may be of therapeutic benefit in the context of C9ALS/FTD. In this study, we found that C9ALS/FTD patients have reduced expression of the AAA+ family members RuvBL1 and RuvBL2, which have both been implicated in aggregate clearance. We report that overexpression of RuvBL1, but to a greater extent RuvBL2, reduced C9orf72-associated DPRs in a range of in vitro systems including cell lines, primary neurons from the C9-500 transgenic mouse model, and patient-derived iPSC motor neurons. In vivo, we further demonstrated that RuvBL2 overexpression and consequent DPR reduction in our Drosophila model was sufficient to rescue a number of DPR-related motor phenotypes. Thus, modulating RuvBL levels to reduce DPRs may be of therapeutic potential in C9ALS/FTD.}, } @article {pmid39638270, year = {2025}, author = {Ruzzante, B and Fruzzetti, F and Cattaneo, M and Lauria Pinter, G and Marcuzzo, S and Candiani, G and Bono, N}, title = {Harnessing osmotic shock for enhanced intracellular delivery of (nano)cargos.}, journal = {International journal of pharmaceutics}, volume = {669}, number = {}, pages = {125008}, doi = {10.1016/j.ijpharm.2024.125008}, pmid = {39638270}, issn = {1873-3476}, mesh = {*Osmotic Pressure ; Humans ; *Cell Survival/drug effects ; Nanoparticles/administration & dosage/chemistry ; Drug Delivery Systems/methods ; Fibroblasts/drug effects/metabolism ; Animals ; Cell Size ; Cell Line ; Cells, Cultured ; }, abstract = {Efficient intracellular delivery of exogenous (nano)materials is critical for both research and therapeutic applications. The physicochemical properties of the cargo play a crucial role in determining internalization efficacy. Consequently, significant research efforts are focused on developing innovative and effective methodologies to optimize (nano)material delivery. In this study, we utilized osmotic shock to enhance (nano)cargos internalization. We examined the effects of hypotonic/hypertonic shock on both primary and cell lines, assessing parameters such as cell viability, cell volume, membrane tension changes, and particle uptake. Our results indicate that short-lived osmotic shock does not harm cells. Hypotonic shock induced temporary shape changes lasting up to 5 min, followed by a 15-minute recovery period. Importantly, hypotonic shock increased the uptake of 100-nm and 500-nm particles by ∼ 3- and ∼ 5-fold, respectively, compared to isotonic conditions. In contrast, the hypertonic shock did not impact cell behavior or particle uptake. Notably, the internalization mechanisms triggered by osmotic shock operate independently of active endocytic pathways, making hypotonic stimulation particularly beneficial for hard-to-treat cells. When primary fibroblasts derived from amyotrophic lateral sclerosis (ALS)-patients were exposed to hypotonic shock in the presence of the therapeutic cargo icerguastat, there was an increased expression of miR-106b-5p compared to isotonic conditions. In conclusion, osmotic shock presents a promising strategy for improving drug delivery within cells and, potentially, in tissues such as muscles or skin, where localized drug administration is preferred.}, } @article {pmid39637982, year = {2025}, author = {Vallée, S and Deneux, V and Funaro, D and Marcoux, D and Powell, J and Hatami, A and Coulombe, J and Piram, M and McCuaig, CC}, title = {Long-term evolution of prepubertal-onset anogenital lichen sclerosus: A 35-year retrospective and cross-sectional study from a single tertiary care maternal and pediatric center.}, journal = {Journal of the American Academy of Dermatology}, volume = {92}, number = {5}, pages = {1010-1014}, doi = {10.1016/j.jaad.2024.09.086}, pmid = {39637982}, issn = {1097-6787}, mesh = {Humans ; Retrospective Studies ; Female ; Child ; Cross-Sectional Studies ; Puberty ; *Vulvar Lichen Sclerosus/diagnosis ; Adolescent ; Quality of Life ; Tertiary Care Centers ; Age of Onset ; *Lichen Sclerosus et Atrophicus/diagnosis ; Disease Progression ; Follow-Up Studies ; Child, Preschool ; Time Factors ; }, abstract = {BACKGROUND: Anogenital lichen sclerosus (ALS) in children may persist after puberty with potential clinical repercussions.

OBJECTIVE: The purpose of this study was to evaluate postpubertal evolution of girls with ALS diagnosed in the prepubertal period based on physical examination, the persistence of functional symptoms, and the effect on quality of life.

METHODS: We retrospectively reviewed 65 cases of girls with prepubertal-onset ALS. Onset, signs/symptoms, photos, evolution, and treatment were collected from the medical records. Subsequently, 30 of these 65 patients were assessed for persistence of signs/symptoms by physical examination and/or standardized questionnaire.

RESULTS: Signs of active disease after puberty based on physical examination were present in 92% (N = 23) of examined patients. A high proportion of cases with persistent ALS after puberty were asymptomatic (47%, N = 14).

LIMITATIONS: This is a single-center retrospective study with a limited number of patients. Half of our original cohort could not be reached or declined a follow-up visit.

CONCLUSION: Prepubertal lichen sclerosus is a chronic condition that can be asymptomatic after puberty despite continued disease activity. We recommend long-term follow-up of patients with prepubertal ALS to prevent associated morbidity.}, } @article {pmid39636751, year = {2025}, author = {Desai, AB and Agarwal, A and Mohamed, AS and Mohamed, KH and Middlebrooks, EH and Bhatt, AA and Gupta, V and Kumar, N and Sechi, E and Flanagan, EP and López Chiriboga, S}, title = {Motor Neuron Diseases and Central Nervous System Tractopathies: Clinical-Radiologic Correlation and Diagnostic Approach.}, journal = {Radiographics : a review publication of the Radiological Society of North America, Inc}, volume = {45}, number = {1}, pages = {e240067}, doi = {10.1148/rg.240067}, pmid = {39636751}, issn = {1527-1323}, mesh = {Humans ; *Motor Neuron Disease/diagnostic imaging ; Diagnosis, Differential ; Magnetic Resonance Imaging/methods ; Pyramidal Tracts/diagnostic imaging ; }, abstract = {White matter tracts within the central nervous system are organized into ascending and descending pathways that transmit sensory input and motor output, respectively. Tractopathy, or damage to these tracts, can impair sensory or motor functions. Motor neuron diseases are pathologic processes affecting the upper or lower motor neurons. Amyotrophic lateral sclerosis (ALS) is the most common form of acquired motor neuron disease. Traditionally, ALS has affected upper and lower motor neurons of the extremities, torso, and head and neck. There are several ALS variants, some of which affect only the upper motor neurons (eg, primary lateral sclerosis), lower motor neurons (eg, progressive muscular atrophy), or motor neurons of the head and neck (eg, progressive bulbar palsy). Characteristic imaging features of ALS include abnormal T2 hyperintensity within the brain along the corticospinal tract, as well as cortical susceptibility signal intensity along the precentral gyrus, termed the "motor band" sign. Spinal muscular atrophy is a less common primary motor neuron disease and appears on images as atrophy of the anterior horn of the spinal cord, as well as proximal muscle atrophy. In addition to pure motor neuron diseases, there are numerous toxic and metabolic conditions, genetic disorders, infectious diseases, and immune-mediated disorders that can secondarily affect the corticospinal tracts (corticospinal tractopathies), producing symptoms of upper motor neuron injury. These tractopathies are visible at MRI as T2-hyperintense lesions along varying segments of the corticospinal tract. A comprehensive diagnostic approach that integrates clinical symptoms with radiologic and laboratory findings is crucial to distinguish among these varied conditions. [©]RSNA, 2024 Supplemental material is available for this article.}, } @article {pmid39636698, year = {2025}, author = {Nona, RJ and Henderson, RD and Mccombe, PA}, title = {Routine blood biochemical biomarkers in amyotrophic lateral sclerosis: Systematic review and cohort analysis.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {26}, number = {3-4}, pages = {303-321}, doi = {10.1080/21678421.2024.2435976}, pmid = {39636698}, issn = {2167-9223}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/blood/mortality/diagnosis ; *Biomarkers/blood ; Cohort Studies ; Creatine Kinase/blood ; Creatinine/blood ; Uric Acid/blood ; }, abstract = {Introduction: Blood biochemical biomarkers, including urate, creatinine, albumin, and creatine kinase, have been shown to be useful in ALS. To provide further information about the roles of these four biomarkers roles we performed a systematic review. In addition, we also performed a new study of the role of these biomarkers in predicting survival, using data from our local ALS cohort. Methods: (1) Using established databases and other sources, we searched for papers about the use of urate, creatinine, albumin, and creatine kinase as biomarkers in ALS. Included articles were reviewed for information about biomarker levels in ALS and controls, association with markers of functional decline, and survival. (2) For our local ALS cohort, we performed survival analysis, Cox-proportionate-hazard ratio and ROC curves to investigate the use of these biomarkers in predicting survival. Results: (1) For systematic review, 104 papers were included. There was some variability in the findings. For urate, there was evidence of decreased levels in ALS, with higher levels associated ith longer survival. For creatinine, there was evidence of decreased levels in ALS, and higher levels correlated with longer survival. For albumin, some reports of reduced levels in ALS, but no consistent association with survival. For creatine kinase, some reports of increased levels in ALS, with inconsistent association with survival. (2) For the local ALS cohort there was evidence that urate and creatinine were associated with survival, but no significant association with survival. There was less evidence for albumin and CK. Discussion: This study provides support for further studies of these readily available biochemical measurement as bioamerkers in ALS.}, } @article {pmid39635310, year = {2024}, author = {Yuan, J and Zhang, YJ and Wen, W and Liu, XC and Chen, FL and Yang, Y}, title = {Afferent loop syndrome of a patient with recurrent fever: A case report.}, journal = {World journal of radiology}, volume = {16}, number = {11}, pages = {678-682}, pmid = {39635310}, issn = {1949-8470}, abstract = {BACKGROUND: Afferent loop syndrome (ALS) is a rare complication, Aoki et al reported that the incidence of distal gastrectomy in Billroth-II is 0.3%-1.0%. The clinical manifestations of ALS are atypical, which can manifest as severe abdominal pain, vomiting, obstructive jaundice, malnutrition, etc.

CASE SUMMARY: The patient was a 58-year-old man who complained of recurrent high fever for more than 1 week. Laboratory tests showed an increase in neutrophil ratio, procalcitonin, C-reactive protein, and abnormal liver function. Enhanced computed tomography scan of the abdomen showed small intestinal obstruction between the anastomosis of the gastrojejunum, bile duct, and pancreaticoduodenum. Gastroscopy revealed significant narrowing of the lumen 15 cm from the anastomosis into the afferent loop. After performing balloon dilation and placement of the nutrition tube, the patient did not experience further fever.

CONCLUSION: ALS is relatively rare after pancreaticoduodenectomy, and the treatment depends on the nature of the obstructive lesion. The traditional treatment method is surgery, and in recent years, endoscopy has provided a new treatment method for ALS.}, } @article {pmid39634573, year = {2024}, author = {Braimah, RO and Taiwo, AO and Olasoji, HO and Legbo, JN and Amundson, M and Ibikunle, AA and Suleiman, IK and Bala, M and Ile-Ogedengbe, BO}, title = {Braimah-Taiwo et al New Classification System and Treatment Algorithm of Mandibulo-Maxillary Synostosis Related to Noma. Field Experience From Noma Children Hospital Sokoto, Nigeria.}, journal = {Craniomaxillofacial trauma & reconstruction}, volume = {17}, number = {4}, pages = {279-290}, pmid = {39634573}, issn = {1943-3875}, abstract = {STUDY DESIGN: This was a retrospective study at Noma Children Hospital, Sokoto, Nigeria, from January 2018 to December 2021.

OBJECTIVE: The main objective of this appraisal was to present Braimah-Taiwo et al's new classification system for mandibulo-maxillary synostosis secondary to noma and also to provide a guide to their treatment.

METHODS: Noma with mandibulo-maxillary synostosis was the main inclusion criteria. Excluded were cases of acute noma and noma without mandibulo-maxillary synostosis. Data retrieved include demographics of patients and extent of bony ankylosis and mandibulo-maxillary synostosis.

RESULTS: A total of 64 patients (30 (46.9%) males and 34 (53.1%) females) were managed. Ages ranged from 6 to 40 years with mean ± SD (18.2 ± 7.6) years. Regarding the new classification system of mandibulo-maxillary synostosis, 6 (9.4%) patients presented with Type 1 (Mild joint obliteration)±Soft tissue scarring, 24 (37.5%) presented with Type II (Total joint obliteration)±Soft tissue scarring, 21 (32.8%) presented with Type III (Coronoid, zygoma and maxilla) ±Soft tissue scarring, 4 (6.3%) presented with Type IV (Condyle, glenoid fossa, coronoid, sigmoid notch and zygoma) ±Soft tissue scarring, 7 (10.9%) presented with Type V (Condyle, glenoid fossa, coronoid, sigmoid notch, zygoma and pterygo-maxilla) ±Soft tissue scarring, while 2 (3.1%) patients presented with Type VI (condyle, glenoid fossa, coronoid, sigmoid notch, zygoma, pterygo-maxilla and the orbit) ±Soft tissue scarring.

CONCLUSIONS: Pattern of tissue destruction in noma patients is complex involving both soft and hard tissues. This new classification will guide surgeons in the effective management of these patients.}, } @article {pmid39633896, year = {2024}, author = {Bhaskaran, S and Piekarz, KM and Brown, J and Yang, B and Ocañas, SR and Wren, JD and Georgescu, C and Bottoms, C and Murphy, A and Thomason, J and Saunders, D and Smith, N and Towner, R and Van Remmen, H}, title = {The nitrone compound OKN-007 delays motor neuron loss and disease progression in the G93A mouse model of amyotrophic lateral sclerosis.}, journal = {Frontiers in neuroscience}, volume = {18}, number = {}, pages = {1505369}, pmid = {39633896}, issn = {1662-4548}, abstract = {Our study investigated the therapeutic potential of OKN-007 in the SOD1 G93A mouse model of amyotrophic lateral sclerosis (ALS). The impact of OKN-007, known for its antioxidant, anti-inflammatory, and neuroprotective properties, was tested at two doses (150 mg/kg and 300 mg/kg) at onset and late-stage disease. Results demonstrated a significant delay in disease progression at both doses, with treated mice showing a slower advance to early disease stages compared to untreated controls. Motor neuron counts in the lumbar spinal cord were notably higher in OKN-007 treated mice at the time of disease onset, suggesting neuroprotection. Additionally, OKN-007 reduced microglial activation and preserved reduced neuromuscular junction fragmentation, although it did not significantly alter the increase in astrocyte number or the decline in hindlimb muscle mass. MR spectroscopy (MRS) revealed improved spinal cord perfusion and normalized myo-inositol levels in treated mice, supporting reduced neuroinflammation. While the expression of several proteins associated with inflammation is increased in spinal cord extracts from G93A mice, OKN-007 dampened the expression of IL-1β, IL-1ra and IL-1α. Despite its promising effects on early-stage disease progression, in general, the beneficial effects of OKN-007 diminished over longer treatment durations. Further, we found no improvement in muscle atrophy or weakness phenotypes in OKN-007 treated G93A mice, and no effect on mitochondrial function or lifespan. Overall, our findings suggest that OKN-007 holds potential as a disease-modifying treatment for ALS, although further research is needed to optimize dosing regimens and understand its long-term effects.}, } @article {pmid39633494, year = {2024}, author = {Ko, VI and Ong, K and Kwon, DY and Li, X and Pietrasiewicz, A and Harvey, JS and Lulla, M and Bhat, G and Cleveland, DW and Ravits, JM}, title = {CK1δ/ε-mediated TDP-43 phosphorylation contributes to early motor neuron disease toxicity in amyotrophic lateral sclerosis.}, journal = {Acta neuropathologica communications}, volume = {12}, number = {1}, pages = {187}, pmid = {39633494}, issn = {2051-5960}, support = {P30 NS047101/NS/NINDS NIH HHS/United States ; S10 OD026929/OD/NIH HHS/United States ; }, mesh = {Animals ; *Amyotrophic Lateral Sclerosis/metabolism/pathology/genetics ; Phosphorylation ; *DNA-Binding Proteins/metabolism/genetics ; *Casein Kinase Idelta/metabolism/genetics ; *Casein Kinase 1 epsilon/metabolism/genetics ; Mice ; Mice, Transgenic ; Disease Models, Animal ; Humans ; Motor Neurons/metabolism/pathology/drug effects ; Mice, Inbred C57BL ; Male ; Mice, Knockout ; }, abstract = {Hyperphosphorylated TDP-43 aggregates in the cytoplasm of motor neurons is a neuropathological signature of amyotrophic lateral sclerosis (ALS). These aggregates have been proposed to possess a toxic disease driving role in ALS pathogenesis and progression, however, the contribution of phosphorylation to TDP-43 aggregation and ALS disease mechanisms remains poorly understood. We've previously shown that CK1δ and CK1ε phosphorylate TDP-43 at disease relevant sites, and that genetic reduction and chemical inhibition could reduce phosphorylated TDP-43 (pTDP-43) levels in cellular models. In this study, we advanced our findings into the hTDP-43-ΔNLS in vivo mouse model of ALS and TDP-43 proteinopathy. This mouse model possesses robust disease-relevant features of ALS, including TDP-43 nuclear depletion, cytoplasmic pTDP-43 accumulation, motor behavior deficits, and shortened survival. We tested the effect of homozygous genetic deletion of Csnk1e in the hTDP-43-ΔNLS mouse model and observed a delay in the formation of pTDP-43 without significant ultimate rescue of TDP-43 proteinopathy or disease progression. Homozygous genetic deletion of Csnk1d is lethal in mice, and we were unable to test the role of CK1δ alone. We then targeted both CK1δ and CK1ε kinases by way of CK1δ/ε-selective PF-05236216 inhibitor in the hTDP-43-ΔNLS mouse model, reasoning that inhibiting CK1ε alone would be insufficient as shown by our Csnk1e knockout mouse model study. Treated mice demonstrated reduced TDP-43 phosphorylation, lowered Nf-L levels, and improved survival in the intermediate stages. The soluble TDP-43 may have been more amenable to the inhibitor treatment than insoluble TDP-43. However, the treatments did not result in improved functional measurements or in overall survival. Our results demonstrate that phosphorylation contributes to neuronal toxicity and suggest CK1δ/ε inhibition in combination with other therapies targeting TDP-43 pathology could potentially provide therapeutic benefit in ALS.}, } @article {pmid39631325, year = {2024}, author = {Zhang, Y and Liu, Q and Xie, H and Zhang, W and Lin, X and Zhang, H and Yu, H and Ma, Y and Zhang, C and Geng, H and Shi, N and Cui, L and Li, B and Li, YF}, title = {Fecal microbiota transplantation as an effective way in treating methylmercury-poisoned rats.}, journal = {The Science of the total environment}, volume = {957}, number = {}, pages = {177850}, doi = {10.1016/j.scitotenv.2024.177850}, pmid = {39631325}, issn = {1879-1026}, mesh = {Animals ; *Methylmercury Compounds/metabolism ; *Fecal Microbiota Transplantation ; Rats ; *Gastrointestinal Microbiome ; Male ; Feces/microbiology ; }, abstract = {Methylmercury (MeHg) can cause devastating neurotoxicity in animals and human beings. Gut microbiota dysbiosis has been found in MeHg-poisoned animals. Fecal microbiota transplantation (FMT) has been shown to improve clinical outcomes in a variety of diseases such as epilepsy, amyotrophic lateral sclerosis (ALS) and autism. The aim of this study was to investigate the effects of FMT on MeHg-poisoned rats. FMT treatment was applied to MeHg-poisoned rats for 14 days. The neurobehavior, weight changes, dopamine (DA), the total Hg and MeHg level were evaluated. Besides, the gut microbiota and metabolites change in feces were also checked. It was found that FMT helped weight gain, alleviated the neurological disorders, enhanced fecal mercury excretion and MeHg demethylation, reconstructed gut microbiome and promoted the production of gut-brain axis related-metabolites in MeHg-poisoned rats. This study elaborates on the therapeutic efficacy of FMT in treating of MeHg-poisoned rats, which sheds lights on the treatment of neurological diseases like Minamata Disease and even Parkinson's Disease.}, } @article {pmid39630626, year = {2024}, author = {Szeky, B and Jurakova, V and Fouskova, E and Feher, A and Zana, M and Karl, VR and Farkas, J and Bodi-Jakus, M and Zapletalova, M and Pandey, S and Kucera, R and Lochman, J and Dinnyes, A}, title = {Efficient derivation of functional astrocytes from human induced pluripotent stem cells (hiPSCs).}, journal = {PloS one}, volume = {19}, number = {12}, pages = {e0313514}, pmid = {39630626}, issn = {1932-6203}, mesh = {*Astrocytes/cytology/metabolism ; Humans ; *Induced Pluripotent Stem Cells/cytology/metabolism ; *Cell Differentiation ; *S100 Calcium Binding Protein beta Subunit/metabolism ; Cytokines/metabolism ; Aquaporin 4/metabolism ; Glial Fibrillary Acidic Protein/metabolism ; Cells, Cultured ; }, abstract = {Astrocytes are specialized glial cell types of the central nervous system (CNS) with remarkably high abundance, morphological and functional diversity. Astrocytes maintain neural metabolic support, synapse regulation, blood-brain barrier integrity and immunological homeostasis through intricate interactions with other cells, including neurons, microglia, pericytes and lymphocytes. Due to their extensive intercellular crosstalks, astrocytes are also implicated in the pathogenesis of CNS disorders, such as ALS (amyotrophic lateral sclerosis), Parkinson's disease and Alzheimer's disease. Despite the critical importance of astrocytes in neurodegeneration and neuroinflammation are recognized, the lack of suitable in vitro systems limits their availability for modeling human brain pathologies. Here, we report the time-efficient, reproducible generation of astrocytes from human induced pluripotent stem cells (hiPSCs). Our hiPSC-derived astrocytes expressed characteristic astrocyte markers, such as GFAP, S100b, ALDH1L1 and AQP4. Furthermore, hiPSC-derived astrocytes displayed spontaneous calcium transients and responded to inflammatory stimuli by the secretion of type A1 and type A2 astrocyte-related cytokines.}, } @article {pmid39630042, year = {2024}, author = {Zinman, L and Duni, E and Abrahao, A}, title = {Rethinking Drug Reimbursement Criteria in Amyotrophic Lateral Sclerosis.}, journal = {The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques}, volume = {51}, number = {5}, pages = {606-607}, doi = {10.1017/cjn.2023.320}, pmid = {39630042}, issn = {0317-1671}, } @article {pmid39629626, year = {2025}, author = {Boutin, RCT and Shobeirian, F and Adam, S and Lehman, A and Salvarinova, R and Friedman, JM}, title = {Immune Dysregulation in a Child With SOD1-Related Neurological Disease.}, journal = {American journal of medical genetics. Part A}, volume = {197}, number = {4}, pages = {e63949}, doi = {10.1002/ajmg.a.63949}, pmid = {39629626}, issn = {1552-4833}, support = {//Mining for Miracles (BCCH Foundation)/ ; //Genome British Columbia/ ; }, mesh = {Humans ; Male ; *Superoxide Dismutase-1/genetics ; Homozygote ; Young Adult ; Phenotype ; *Nervous System Diseases/genetics/immunology/pathology ; *Quadriplegia/genetics/pathology/immunology ; Child ; Mutation ; }, abstract = {Spastic tetraplegia and axial hypotonia (STAHP) associated with biallelic SOD1 deficiency is a recently described neurological disorder affecting children. Five studies have described a total of nine cases thus far, all characterized by the onset of progressive spastic tetraplegia beginning before 2 years of age. All but two of these cases are associated with homozygosity for the same genetic variant (NM_000454.4:c.335dupG; NP_000445.1:p.Cys112Trpfs*11) that leads to a non-functional enzyme product. More recently, a homozygous 3-base pair in-frame deletion (NM_000454.5: c.357_357+2delGGT) and a truncating frameshift variant (NM_000454.5: c.52_56del5ins154) in SOD1 have been described in similarly affected patients lacking SOD1 activity. Here we expand on the neurological and extra-neuronal phenotypes of STAHP in a patient with a novel homozygous SOD1 variant predicted to result in disrupted calcium- and zinc-binding activity of the encoded enzyme. We describe a 19-year-old male born to consanguineous parents who is homozygous for an NM_000454.4:c.369_371del SOD1 variant. The patient had progressive neuromuscular degeneration with onset before 1 year of age, consistent with a diagnosis of STAHP. Brain MRI at 7 years of age showed cerebellar atrophy, as has previously been described in this condition, as well as small optic nerves and a hypoplastic optic chiasm, which have not been reported previously. Our patient also exhibited clinical features of immune dysregulation with treatment-refractory inflammatory bowel disease, asthma, recurrent infections, and dermatitis. Overall, the early-onset progressive neurological disorder in our patient, found in association with homozygosity for an SOD1 variant that is predicted to result in impaired function of the transcribed protein, is consistent with a diagnosis of STAHP. Our patient also demonstrates optic atrophy and disrupted immune homeostasis, which have not been previously described as part of this condition. Taken together with previous case studies in children carrying loss-of-function variants of SOD1, this case highlights a possible role for antioxidant therapy in slowing disease progression in patients lacking SOD1 activity. These cases also draw attention to the need for careful consideration of possible harmful neuronal and extra-neuronal complications of proposed SOD1 knockdown therapies against ALS.}, } @article {pmid39628898, year = {2024}, author = {Stansberry, WM and Fiur, NC and Robins, MM and Pierchala, BA}, title = {Analysis of translatomic changes in the Ubqln2[P497S] model of ALS reveals that motor neurons express muscle-associated genes in non-disease states.}, journal = {Frontiers in neurology}, volume = {15}, number = {}, pages = {1491415}, pmid = {39628898}, issn = {1664-2295}, support = {T32 AG071444/AG/NIA NIH HHS/United States ; }, abstract = {INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by progressively worsening motor symptoms that lead to eventual fatal paralysis. The number of gene mutations associated with ALS have increased dramatically in recent years, suggesting heterogeneity in the etiology of ALS and the need to develop new models of the disease that encompass these pathologies. In 2011, mutations in the UBQLN2 gene were identified in families with both ALS and frontotemporal dementia (FTD) and have since been linked to ubiquitinated TDP43 inclusion pathology. The involvement of UBQLN2 in ubiquitination and proteasome function suggests an important role in proteostasis, which is reported to be impaired in ALS.

METHODS: A UBQLN2 mouse model was generated for the P497S mutation and recapitulates some of the motor symptoms of ALS. We utilized ribosomal profiling followed by mRNA sequencing of associated transcripts to characterize gene expression changes of motor neurons in the Ubqln2[P497S] model and evaluated ALS phenotypes in these animals.

RESULTS: At 12 months of age, we observed reduced motor neuron survival and neuromuscular junction denervation in these mice that translated into motor deficits observed in locomotor behavioral trials. The sequencing of motor neuron transcripts revealed that Wnt pathways and muscle-related transcripts were downregulated in Ubqln2[P497S] mice, while metabolic pathways were upregulated.

DISCUSSION: Surprisingly, genes often reported to be muscle-specific, such as Desmin and Acta1, were expressed in motor neurons and were dramatically downregulated in symptomatic Ubqln2[P497S] mice. The expression of muscle transcripts by motor neurons suggests their potentially supportive role in skeletal muscle maintenance.}, } @article {pmid39628659, year = {2024}, author = {Ye, Q and Li, X and Gao, W and Gao, J and Zheng, L and Zhang, M and Yang, F and Li, H}, title = {Role of Rho-associated kinases and their inhibitor fasudil in neurodegenerative diseases.}, journal = {Frontiers in neuroscience}, volume = {18}, number = {}, pages = {1481983}, pmid = {39628659}, issn = {1662-4548}, abstract = {Neurodegenerative diseases (NDDs) are prevalent in the elderly. The pathogenesis of NDDs is complex, and currently, there is no cure available. With the increase in aging population, over 20 million people are affected by common NDDs alone (Alzheimer's disease and Parkinson's disease). Therefore, NDDs have profound negative impacts on patients, their families, and society, making them a major global health concern. Rho-associated kinases (ROCKs) belong to the serine/threonine protein kinases family, which modulate diverse cellular processes (e.g., apoptosis). ROCKs may elevate the risk of various NDDs (including Huntington's disease, Parkinson's disease, and Alzheimer's disease) by disrupting synaptic plasticity and promoting inflammatory responses. Therefore, ROCK inhibitors have been regarded as ideal therapies for NDDs in recent years. Fasudil, one of the classic ROCK inhibitor, is a potential drug for treating NDDs, as it repairs nerve damage and promotes axonal regeneration. Thus, the current review summarizes the relationship between ROCKs and NDDs and the mechanism by which fasudil inhibits ROCKs to provide new ideas for the treatment of NDDs.}, } @article {pmid39627937, year = {2024}, author = {Gielas, AM}, title = {Wounds and Vulnerabilities. The Participation of Special Operations Forces in Experimental Brain-Computer Interface Research.}, journal = {Cambridge quarterly of healthcare ethics : CQ : the international journal of healthcare ethics committees}, volume = {}, number = {}, pages = {1-22}, doi = {10.1017/S096318012400063X}, pmid = {39627937}, issn = {1469-2147}, abstract = {Brain-computer interfaces (BCIs) exemplify a dual-use neurotechnology with significant potential in both civilian and military contexts. While BCIs hold promise for treating neurological conditions such as spinal cord injuries and amyotrophic lateral sclerosis in the future, military decisionmakers in countries such as the United States and China also see their potential to enhance combat capabilities. Some predict that U.S. Special Operations Forces (SOF) will be early adopters of BCI enhancements. This article argues for a shift in focus: the U.S. Special Operations Command (SOCOM) should pursue translational research of medical BCIs for treating severely injured or ill SOF personnel. After two decades of continuous military engagement and on-going high-risk operations, SOF personnel face unique injury patterns, both physical and psychological, which BCI technology could help address. The article identifies six key medical applications of BCIs that could benefit wounded SOF members and discusses the ethical implications of involving SOF personnel in translational research related to these applications. Ultimately, the article challenges the traditional civilian-military divide in neurotechnology, arguing that by collaborating more closely with military stakeholders, scientists can not only help individuals with medical needs, including servicemembers, but also play a role in shaping the future military applications of BCI technology.}, } @article {pmid39627617, year = {2024}, author = {Wiersema, AF and Rennenberg, A and Smith, G and Varderidou-Minasian, S and Pasterkamp, RJ}, title = {Shared and distinct changes in the molecular cargo of extracellular vesicles in different neurodegenerative diseases.}, journal = {Cellular and molecular life sciences : CMLS}, volume = {81}, number = {1}, pages = {479}, pmid = {39627617}, issn = {1420-9071}, support = {XS grant//Nederlandse Organisatie voor Wetenschappelijk Onderzoek/ ; GoALS//Stichting ALS Nederland/ ; TOTALS//Stichting ALS Nederland/ ; MUSALS//Stichting ALS Nederland/ ; ATAXALS//Stichting ALS Nederland/ ; MAXOMOD//E-rare3/ ; INTEGRALS//Rare-3/ ; TRIAGE//JPND/ ; }, mesh = {Animals ; Humans ; Alzheimer Disease/metabolism/pathology ; Amyloid beta-Peptides/metabolism ; Amyotrophic Lateral Sclerosis/metabolism/pathology ; Biomarkers/analysis/metabolism ; *Cell Communication ; *Extracellular Vesicles/metabolism ; MicroRNAs/metabolism/genetics ; *Neurodegenerative Diseases/diagnosis/metabolism/pathology ; Parkinson Disease/metabolism/pathology ; tau Proteins/metabolism ; }, abstract = {Neurodegenerative disorders such as Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS) and Parkinson's disease (PD) affect millions of people worldwide. Curative treatment for these neurodegenerative disorders is still lacking and therefore a further understanding of their cause and progression is urgently needed. Extracellular vesicles (EVs) are nanosized vesicles loaded with cargo, such as proteins and miRNAs, that are released by cells and play an important role in intercellular communication. Intercellular communication through EVs can contribute to the spread of pathological proteins, such as amyloid-beta and tau, or cause pathogenesis through other mechanisms. In addition, EVs may serve as potential biomarkers for diagnosis and for monitoring disease progression. In this review, we summarize and discuss recent advances in our understanding of the role of EVs in AD, ALS an PD with an emphasis on dysregulated cargo in each disease. We highlight shared dysregulated cargo between these diseases, discuss underlying pathways, and outline future implications for therapeutic strategies.}, } @article {pmid39624969, year = {2024}, author = {Yuan, D and Jiang, S and Xu, R}, title = {Clinical features and progress in diagnosis and treatment of amyotrophic lateral sclerosis.}, journal = {Annals of medicine}, volume = {56}, number = {1}, pages = {2399962}, pmid = {39624969}, issn = {1365-2060}, mesh = {*Amyotrophic Lateral Sclerosis/diagnosis/therapy/epidemiology/genetics ; Humans ; Prognosis ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease of the central nervous system. Despite a large number of studies, the current prognosis of ALS is still not ideal. This article briefly describes the clinical features including epidemiology, genetic structure and clinical manifestations, as well as the progress of new diagnostic criteria and treatment of ALS. Meanwhile, we also discussed further both developments and improvements to enhance understanding and accelerating the introduction of the effective treatments of ALS.}, } @article {pmid39624674, year = {2024}, author = {Nakamura, K and Fujita, K and Suzuki, M and Kunugi, A and Hirozane, Y and Kunikata, T and Takahashi, B and Narazaki, G and Kondo, H and Haji, S and Hirai, K and Izumi, Y}, title = {Neuroinflammation and glycosylation-related cerebrospinal fluid proteins for predicting functional decline in amyotrophic lateral sclerosis: a proteomic study.}, journal = {Frontiers in neurology}, volume = {15}, number = {}, pages = {1418320}, pmid = {39624674}, issn = {1664-2295}, abstract = {BACKGROUND: The rate of disease progression varies widely among patients with amyotrophic lateral sclerosis (ALS). Prognostic assessment using biomarkers is highly anticipated to improve clinical trial design. We aimed to explore the cerebrospinal fluid (CSF) for prognostic biomarkers to predict future functional decline in patients with ALS.

METHODS: We collected CSF samples from 64 patients with ALS and 25 disease controls. The prospective progression rate was calculated using the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) at CSF collection and in 6 months. The ALS patients were classified into slow, intermediate, and fast progression groups. We performed comprehensive proteomic analyses of the CSF samples. Factors with significant changes between slow and fast progression groups were investigated via receiver operating characteristic curve analyses. Moreover, the correlation of the CSF factors with progression rate was evaluated by multiple regression analyses.

RESULTS: In total, 26 proteins changed significantly (p < 0.05 and q < 0.10), with levels varying within a large dynamic range (fold change of >1.5 or < 0.5). A receiver operating characteristic curve analyses showed that the following proteins showed high discrimination power between slow and fast progression groups: glycoprotein non-metastatic melanoma protein B (GPNMB; area under the curve [AUC], 0.88), glial fibrillary acidic protein (AUC, 0.81), glypican-1 (GPC1; AUC, 0.79), alpha-1,6-mannosyl-glycoprotein 2-beta-N-acetylglucosaminyltransferase (AUC, 0.74), and chitinase-3-like protein 2 (CHI3L2; AUC, 0.73). Of these, GPNMB, GPC1, and CHI3L2 were significantly correlated to prognostic progression rate.

CONCLUSION: This study demonstrated that CSF levels of neuroinflammation and glycosylation-related proteins were significantly correlated with prospective progression rates in patients with ALS. These proteins could be useful prognostic biomarkers for ALS.}, } @article {pmid39623504, year = {2024}, author = {Gupta, R and Bhandari, M and Grover, A and Al-Shehari, T and Kadrie, M and Alfakih, T and Alsalman, H}, title = {Predictive modeling of ALS progression: an XGBoost approach using clinical features.}, journal = {BioData mining}, volume = {17}, number = {1}, pages = {54}, pmid = {39623504}, issn = {1756-0381}, support = {RSP2024R244//King Saud University/ ; }, abstract = {This research presents a predictive model aimed at estimating the progression of Amyotrophic Lateral Sclerosis (ALS) based on clinical features collected from a dataset of 50 patients. Important features included evaluations of speech, mobility, and respiratory function. We utilized an XGBoost regression model to forecast scores on the ALS Functional Rating Scale (ALSFRS-R), achieving a training mean squared error (MSE) of 0.1651 and a testing MSE of 0.0073, with R[2] values of 0.9800 for training and 0.9993 for testing. The model demonstrates high accuracy, providing a useful tool for clinicians to track disease progression and enhance patient management and treatment strategies.}, } @article {pmid39623474, year = {2024}, author = {Hoyle, AC and Stevenson, R and Leonhardt, M and Gillett, T and Martinez-Hernandez, U and Gompertz, N and Clarke, C and Cazzola, D and Metcalfe, BW}, title = {Exploring the 'EarSwitch' concept: a novel ear based control method for assistive technology.}, journal = {Journal of neuroengineering and rehabilitation}, volume = {21}, number = {1}, pages = {210}, pmid = {39623474}, issn = {1743-0003}, mesh = {Humans ; Female ; Male ; Adult ; Middle Aged ; *Self-Help Devices ; Aged ; Tensor Tympani/physiology ; Young Adult ; Nervous System Diseases/rehabilitation ; Adolescent ; Motor Neuron Disease/rehabilitation ; Communication Devices for People with Disabilities ; Muscle Contraction/physiology ; Multiple Sclerosis/rehabilitation ; }, abstract = {BACKGROUND: Loss of communication with loved ones and carers is one of the most isolating and debilitating effects of many neurological disorders. Assistive technology (AT) supports individuals with communication, but the acceptability of AT solutions is highly variable. In this paper a novel ear based control method of AT, the concept of 'EarSwitch', is presented. This new approach is based on detecting ear rumbling, which is the voluntary contraction of the tensor tympani muscle (TTM), resulting in observable movement of the eardrum and a dull rumbling sound. 'EarSwitch' has the potential to be a discreet method that can complement existing AT control methods. However, only a subset of the population can ear rumble and little is known about the ability of rumbling in populations with neurological disorders.

METHODS: To explore the viability of the 'EarSwitch' concept as an AT control method we conducted in-depth online surveys with (N=1853) respondents from the general population and (N=170) respondents with self-declared neurological disorders including Motor Neurone Disease (MND) and Multiple Sclerosis (MS).This is the largest ever study to explore ear rumbling and the first to explore whether rumbling is preserved among individuals with neurological disorders. In addition, we validated rumbling, and investigated usability of the 'EarSwitch' concept as a control input, using in-person otoscopic examination with a subset of participants.

RESULTS: A significant proportion of the population with neurological disorders could benefit from 'EarSwitch' controllable AT. The upper bound prevalence of the ability to rumble without accompanying movements was 55% in the general population, 38% in the neurological population, and 20% of participants with MND (N=95) reported this ability. During the validation procedure, participants achieved high accuracy in self-reporting the ability to rumble (80%) and proved concept of using the 'EarSwitch' method to control a basic interface.

DISCUSSION: 'EarSwitch' is a potential new AT control method control, either by itself or as a supplement to other existing methods. Results demonstrate self-reported ear rumbling is present among patients with different neurological disorders, including MND. Further research should explore how well the ability to rumble is preserved in different types and stages of neurological disorders.}, } @article {pmid39622292, year = {2025}, author = {Ojo, O and Boateng, J and Pacella, R and Hanrahan, A and Essex, R and Dibley, L}, title = {Factors Influencing the Care and Management of Diabetic Foot Ulcers: A Scoping Review.}, journal = {Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists}, volume = {31}, number = {3}, pages = {380-389}, doi = {10.1016/j.eprac.2024.11.010}, pmid = {39622292}, issn = {1530-891X}, mesh = {Humans ; *Diabetic Foot/therapy ; *Health Knowledge, Attitudes, Practice ; Patient Education as Topic ; Disease Management ; }, abstract = {OBJECTIVE: The objective of this scoping review is to explore the experiences of patients' and healthcare practitioners on the factors that influence the care and management of diabetes-related foot ulcers (DFUs).

METHODS: Levac et al's 6-stage framework and the Preferred Reporting Items for Systematic Review and Meta-analysis extension for scoping reviews, guided the review. The SPIDER tool was used to define key elements of the review question. Searches for relevant articles were conducted in electronic databases (PUBMED, CINAHL, AMED, Embase, Cochrane Database of Systematic Reviews, and PsycINFO), Google Scholar, and hand searches of reference lists.

RESULTS: Eight articles met the inclusion criteria and were included in the review. Three themes were identified: Communication and Education about DFUs; Challenges of managing DFUs; and Barriers to treatment and management. The themes are presented as a narrative synthesis.

CONCLUSION: Inadequate knowledge of diabetic foot care by patients and inconsistent communication by healthcare professionals were primary factors affecting the effective management of diabetes-related foot ulcers. Consistent, patient-focused education that is supported by knowledgeable health care professionals should form the foundation of effective diabetic foot ulcer care.}, } @article {pmid39621905, year = {2024}, author = {Van Nerom, M and Ahmed, J and Lazar, T and Meszaros, A and Galand, Q and De Malsche, W and Van Lindt, J and Pancsa, R and Maes, D and Tompa, P}, title = {C9orf72-linked arginine-rich dipeptide repeats aggravate pathological phase separation of G3BP1.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {121}, number = {50}, pages = {e2402847121}, pmid = {39621905}, issn = {1091-6490}, support = {952334//EC | Horizon 2020 Framework Programme (H2020)/ ; 778247//EC | Horizon 2020 Framework Programme (H2020)/ ; K124670//National Research, Development and Innovation Office/ ; K131702//National Research, Development and Innovation Office/ ; SRP51//Vrije Universiteit Brussel (VUB)/ ; A0-2004-070//European Space Agency (ESA)/ ; FWOSB77//Fonds Wetenschappelijk Onderzoek (FWO)/ ; 11D2522N//Fonds Wetenschappelijk Onderzoek (FWO)/ ; HBC.2022.0194//Agentschap Innoveren en Ondernemen (VLAIO)/ ; FK-142285//National Research, Development and Innovation Office/ ; BO/00174/22//Magyar Tudományos Akadémia (MTA)/ ; 184018//Tempus Közalapítvány (TPF)/ ; }, mesh = {*RNA Recognition Motif Proteins/metabolism/genetics/chemistry ; *Poly-ADP-Ribose Binding Proteins/metabolism/genetics/chemistry ; Humans ; *C9orf72 Protein/genetics/metabolism ; *RNA Helicases/metabolism/genetics ; *Amyotrophic Lateral Sclerosis/metabolism/genetics ; *Dipeptides/metabolism/chemistry ; *DNA Helicases/metabolism/genetics ; *Arginine/metabolism/chemistry ; *Nucleophosmin/genetics ; Frontotemporal Dementia/metabolism/genetics/pathology ; Stress Granules/metabolism ; DNA-Binding Proteins/metabolism/genetics/chemistry ; Heterogeneous Nuclear Ribonucleoprotein A1/metabolism/genetics ; Protein Binding ; Phase Separation ; }, abstract = {The toxic effects of C9orf72-derived arginine-rich dipeptide repeats (R-DPRs) on cellular stress granules in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia remain unclear at the molecular level. Stress granules are formed through the switch of Ras GTPase-activating protein-binding protein 1 (G3BP1) by RNA from a closed inactive state to an open activated state, driving the formation of the organelle by liquid-liquid phase separation (LLPS). We show that R-DPRs bind G3BP1 a thousand times stronger than RNA and initiate LLPS much more effectively. Their pathogenic effect is underscored by the slow transition of R-DPR-G3BP1 droplets to aggregated, ThS-positive states that can recruit ALS-linked proteins hnRNPA1, hnRNPA2, and TDP-43. Deletion constructs and molecular simulations show that R-DPR binding and LLPS are mediated via the negatively charged intrinsically disordered region 1 (IDR1) of the protein, allosterically regulated by its positively charged IDR3. Bioinformatic analyses point to the strong mechanistic parallels of these effects with the interaction of R-DPRs with nucleolar nucleophosmin 1 (NPM1) and underscore that R-DPRs interact with many other similar nucleolar and stress-granule proteins, extending the underlying mechanism of R-DPR toxicity in cells. Our results also highlight characteristic differences between the two R-DPRs, poly-GR and poly-PR, and suggest that the primary pathological target of poly-GR is not NPM1 in nucleoli, but G3BP1 in stress granules in affected cells.}, } @article {pmid39621705, year = {2024}, author = {Foldvari, KM and Stolee, P and Neiterman, E and Boscart, V and Tong, C}, title = {"…but I know something's not right here": Exploring the diagnosis and disclosure experiences of persons living with ALS.}, journal = {PloS one}, volume = {19}, number = {12}, pages = {e0301249}, pmid = {39621705}, issn = {1932-6203}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/psychology/diagnosis ; Female ; Male ; Middle Aged ; Aged ; *Caregivers/psychology ; Disclosure ; Focus Groups ; Truth Disclosure ; }, abstract = {BACKGROUND: Amyotrophic Lateral Sclerosis (ALS), an incurable motor neuron disease, primarily affects those between the ages of 60-79, and has an approximate post-diagnosis life-expectancy of only two to five years. The condition has an unpredictable but ultimately terminal trajectory that poses challenges for patients, caregivers and healthcare providers. While the diagnosis and disclosure are critical periods for intervention and support, knowledge regarding the relational, communicational and psychodynamic forces that occur within the process of diagnostic disclosure is relatively limited.

OBJECTIVES: The purpose of this study was to explore the experiences of persons living with ALS in the diagnosis and disclosure of the condition, with the support of their caregivers.

METHODS: We conducted a focus group and in-depth individual interviews with people living with ALS (n = 9), and caregivers (n = 9). The interviews were transcribed, cleaned, and anonymized, and then entered into NVivo 11 for thematic analysis.

RESULTS: Participants discussed the diagnostic process, including inklings and subtle changes prior to diagnosis, attempts at self-diagnosis, and the lengthy assessment process. Time was also a consideration in the diagnostic disclosure process, in which participants shared how the disclosure was the product of longstanding conversations with their care providers. It was described as rarely a shock to finally have confirmation. Participants shared their information seeking strategies and needs for a diagnosis that, for them, typically came with insufficient information on the disease, prognosis, and next steps.

SIGNIFICANCE: This project serves as a step in bridging the relevant gaps in our knowledge and understanding towards improved person-centered care practices in the diagnosis and disclosure of ALS.}, } @article {pmid39621126, year = {2024}, author = {Mikhailova, MM and Klein, OI and Patsaev, TD and Panteleyev, AA}, title = {Co-culture of postnatal mouse spinal cord and skeletal muscle explants as an experimental model of neuromuscular interactions.}, journal = {Histochemistry and cell biology}, volume = {163}, number = {1}, pages = {15}, pmid = {39621126}, issn = {1432-119X}, support = {1п.2.3//National Research Center "Kurchatov Institute"/ ; 1п.2.3//National Research Center "Kurchatov Institute"/ ; 1п.2.3//National Research Center "Kurchatov Institute"/ ; 1п.2.3//National Research Center "Kurchatov Institute"/ ; }, mesh = {Animals ; Mice ; *Muscle, Skeletal/metabolism ; *Coculture Techniques ; *Spinal Cord/metabolism ; Mice, Inbred C57BL ; Animals, Newborn ; }, abstract = {The intercommunication between nerves and muscles plays an important role in the functioning of our body, and its failure leads to severe neuromuscular disorders such as spinal muscular atrophy and amyotrophic lateral sclerosis. Understanding the cellular and molecular mechanisms underlying nerve-muscle interactions and mediating their mutual influence is an integral part of strategies aimed at curing neuromuscular diseases. Here, we propose a novel ex vivo experimental model for the spinal cord (SC) and skeletal muscle interactions which for the first time utilizes only fully formed (but not yet quite functional) postnatal tissues. The model represents an organotypic co-culture comprising a longitudinal slice of the mouse postnatal SC and an extensor digitorum longus (EDL) muscle explant placed in the "damage zone" of transversally dissected longitudinal slice of the SC. Using this model, we have shown that SC tissue stimulates muscle contractions and reduces the area occupied by acetylcholine receptors on muscle surface. In turn, EDL muscles stimulate the growth of SC-derived neurites. Thus, our organotypic model allows one to assess the mutual influence of neurons and muscles in a nearly natural setting which maintains the architecture and cellular composition of intact tissues. Therefore, this model may provide an effective platform for studying molecular and cellular mechanisms linked to defective neuromuscular interactions in associated pathologies.}, } @article {pmid39620262, year = {2025}, author = {Chen, Y and Sun, S and Yun, Y and Sun, X and Xin, J and Shao, K and Lin, P and Yu, D and Yan, C and Liu, S}, title = {Connectivity-based striatal subregion microstructural changes in sporadic amyotrophic lateral sclerosis patients: Relation to motor disability, cognitive deficits, and serum biomarkers.}, journal = {European journal of neurology}, volume = {32}, number = {1}, pages = {e16577}, pmid = {39620262}, issn = {1468-1331}, support = {2020M672067//China Postdoctoral Science Foundation/ ; NSFC82001354//National Natural Science Foundation of China/ ; NSFC82471395//National Natural Science Foundation of China/ ; ZR2023LSW020//Shandong Provincial Natural Science Foundation/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/blood/diagnostic imaging/pathology ; Male ; Female ; Middle Aged ; Aged ; *Biomarkers/blood ; *Cognitive Dysfunction/blood/etiology/diagnostic imaging/pathology/physiopathology ; Retrospective Studies ; *Corpus Striatum/diagnostic imaging/pathology ; Adult ; Neurofilament Proteins/blood ; Diffusion Tensor Imaging ; Diffusion Magnetic Resonance Imaging ; }, abstract = {BACKGROUND AND PURPOSE: To date, no previous studies have used multishell diffusion MRI to identify striatal microstructural damage in vivo in amyotrophic lateral sclerosis (ALS) patients. Thus, in the present study, we aimed to comprehensively explore connectivity-based selective striatal subregion microstructural damage in sporadic ALS patients and its associations with motor disability, cognitive deficits, and serum biomarkers.

METHODS: In this retrospective study, 79 ALS patients and 53 healthy controls (HCs) who underwent clinical assessment, serum neurofilament light (NfL) measurement, genetic testing, and multishell diffusion MRI scanning were included. Using a probabilistic tractography approach, the striatum was segmented into six subregions based on their corticostriatal connectivity. Three neurite orientation dispersion and density imaging (NODDI) parameters, the neurite density index (NDI), orientation dispersion index (ODI), and isotropic volume fraction (ISO), of the connectivity-based striatal subregions were measured.

RESULTS: Compared with HCs, ALS patients had a significantly lower NDI in the bilateral motor and right frontal subregions, a significantly lower ODI in the right motor and frontal subregions, and a significantly higher ISO in the bilateral motor and frontal subregions of the striatum after familywise error (p < 0.05). Moreover, striatal subregion microstructural damage was significantly correlated with motor disabilities, cognitive deficits, and serum NfL levels in ALS patients (p = 0.020-0.002).

CONCLUSIONS: Our study provides clear evidence demonstrating that connectivity-based selective striatal subregion microstructural damage is a definite feature of sporadic ALS patients and suggesting that striatal damage may play an important role in motor disability and cognitive deficits in ALS patients.}, } @article {pmid39617896, year = {2024}, author = {Feng, R and Zhu, Q and Wang, A and Wang, H and Wang, J and Chen, P and Zhang, R and Liang, D and Teng, J and Ma, M and Ding, X and Wang, X}, title = {Effect of fecal microbiota transplantation on patients with sporadic amyotrophic lateral sclerosis: a randomized, double-blind, placebo-controlled trial.}, journal = {BMC medicine}, volume = {22}, number = {1}, pages = {566}, pmid = {39617896}, issn = {1741-7015}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy ; *Fecal Microbiota Transplantation/methods ; Double-Blind Method ; Female ; Male ; Middle Aged ; Aged ; Gastrointestinal Microbiome/physiology ; Treatment Outcome ; Quality of Life ; Adult ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder marked by the progressive loss of motor neurons. Recent insights into ALS pathogenesis underscore the pivotal role of the gut microbiome, prompting an investigation into the potential therapeutic impact of fecal microbiota transplantation (FMT) on sporadic ALS patients.

METHODS: Conducted as a double-blind, placebo-controlled, parallel-group, randomized clinical trial, the study enrolled 27 participants from October 2022 to April 2023. The participants were followed up for 6 months from February 2023 to October 2023, during in-person visits at baseline, week 15, week 23, and week 35. The participants, evenly randomized, received either healthy donor FMT (FMT, n = 14) or a mixture of 0.9% saline and food coloring (E150c) as sham transplantation (placebo, n = 13). The primary outcome measured the change in the ALS Functional Rating Scale-Revised (ALSFRS-R) total score from baseline to week 35. Secondary outcomes included changes in gastrointestinal and respiratory functions, muscle strength, autonomic function, cognition, quality of life, intestinal microbiome composition, and plasm neurofilament light chain protein (NFL). Efficacy and safety outcomes were assessed in the intention-to-treat population.

RESULTS: A total of 27 randomized patients (47% women; mean age, 67.2 years), 24 participants completed the entire study. Notably, ALSFRS-R score changes exhibited no significant differences between FMT (6.1 [SD, 3.11]) and placebo (6.41[SD, 2.73]) groups from baseline to week 35. Secondary efficacy outcomes, encompassing respiratory function, muscle strength, autonomic function, cognition, quality of life, and plasm NFL, showed no significant differences. Nevertheless, the FMT group exhibited improvements in constipation, depression, and anxiety symptoms. FMT induced a shift in gut microbiome community composition, marked by increased abundance of Bifidobacterium, which persisted until week 15 (95% CI, 0.04 to 0.28; p = 0.01). Gastrointestinal adverse events were the primary manifestations of FMT-related side effects.

CONCLUSIONS: In this clinical trial involving 27 sporadic ALS patients, FMT did not significantly slow the decline in ALSFRS-R score. Larger multicenter trials are needed to confirm the efficacy of FMT in sporadic ALS patients and to explore the underlying biological mechanisms.

TRIAL REGISTRATION: Chinese Clinical Trial Registry Identifier: ChiCTR 2200064504.}, } @article {pmid39617118, year = {2025}, author = {Liang, YF and Niu, ZX and Wu, ZW and Zhang, QY and Zhao, XY and Chao, LL and Li, H and Gao, WY}, title = {Catalytic insights of acetolactate synthases from different bacteria.}, journal = {Archives of biochemistry and biophysics}, volume = {764}, number = {}, pages = {110248}, doi = {10.1016/j.abb.2024.110248}, pmid = {39617118}, issn = {1096-0384}, mesh = {*Acetolactate Synthase/chemistry/metabolism/genetics ; *Bacillus subtilis/enzymology ; Molecular Docking Simulation ; *Klebsiella pneumoniae/enzymology ; *Listeria/enzymology ; Pyruvic Acid/metabolism/chemistry ; Substrate Specificity ; *Bacterial Proteins/chemistry/metabolism/genetics ; Amino Acid Sequence ; Butyrates ; }, abstract = {Acetolactate synthase (ALS) is an essential enzyme involved in the biosynthesis of platform chemicals acetoin and 2,3-butanediol in several microorganisms. In this study, we investigated the catalytic differences among three bacterial ALSs involved in the ligation of two molecules of pyruvate or 2-ketobutyrate. Based on the findings, we predicted three amino acid residues in each enzyme that caused a discrepancy in accordance with the multi-sequence alignment and molecular docking experiments: I398, A402, and T480 in Bacillus subtilis ALS; V400, Y404, and S482 in Listeria seleigeri serovar 1/2b ALS; and M394, H398, and G476 in Klebsiella pneumoniae ALS. Subsequently, we mutually mutated the residues in the three ALSs. The data obtained confirmed our inference that these three residues in each enzyme are truly correlated with substrate recognition, particularly in recognizing compounds that are larger than pyruvate, such as 2-ketobutyrate, benzaldehyde, and nitrosobenzene. This study further clarifies the biochemical traits of ALSs derived from various bacteria and expands the scope of ALS research.}, } @article {pmid39616922, year = {2024}, author = {Santurtún, A and Medín, P and Riancho, JA and Santiago-Setién, M and Ortiz, F and López de Munain, A and Almendra, R and Riancho, J}, title = {Temporo-spatial analysis of amyotrophic lateral sclerosis in Spain: Altitude and land use as new determinants of the disease.}, journal = {The Science of the total environment}, volume = {957}, number = {}, pages = {177796}, doi = {10.1016/j.scitotenv.2024.177796}, pmid = {39616922}, issn = {1879-1026}, mesh = {*Amyotrophic Lateral Sclerosis/epidemiology/mortality ; Spain/epidemiology ; Humans ; Male ; Female ; *Altitude ; Spatio-Temporal Analysis ; Middle Aged ; Aged ; Incidence ; Adult ; }, abstract = {INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is the most common neurodegenerative disease affecting motor neurons. Currently, ALS is conceived as the result of the interaction between genetics, environmental factors, and aging. This study analyzed the spatial and temporal patterns of ALS in Spain, delving into the potential relationships between altitude, land cover, and this disease.

METHODOLOGY: ALS death data were collected over a 19-year period, including information on sex, age and municipality of residence. The standardized mortality rate was calculated for each municipality of residencia, and Anselin's local Moran's I statistic was used to identify clusters of high and low incidence. Altitude data were sourced from the Copernicus Land Monitoring Services, while land cover data came from CORINE satellite images and national agricultural statistics.

RESULTS: The average annual incidence of ALS deaths among adults was 2.5 per 100,000 people. Higher mortality rates were noted in males (2.8) than in females (2.3), with both sexes exhibiting a rising mortality trend in a temporal analysis. Cluster analysis revealed that high mortality areas were mostly located in the North and Northeast of the country. Municipalities in these clusters had significantly lower median altitudes and larger areas of Permanently Irrigated Arable Land and Broad-Leaved Forest.

CONCLUSION: This study provides new evidence about the increase in ALS cases in European countries during the last decades, reporting for the first time altitude and certain agricultural land uses as potential geographic determinants of the disease.}, } @article {pmid39616446, year = {2025}, author = {Rutkove, SB and McIlduff, CE and Stommel, E and Levy, S and Smith, C and Gutierrez, H and Verga, S and Samaan, S and Yator, C and Nanda, A and Sonbas-Cobb, B and Capella, T and Pastel, L and Doussan, A and Phipps, K and Murphy, E and Halter, R}, title = {Thoracic electrical impedance tomography for assessing progression of pulmonary dysfunction in ALS.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {26}, number = {3-4}, pages = {296-302}, pmid = {39616446}, issn = {2167-9223}, support = {R21 NS118434/NS/NINDS NIH HHS/United States ; }, mesh = {Humans ; Male ; *Amyotrophic Lateral Sclerosis/complications/physiopathology/diagnostic imaging ; Female ; *Electric Impedance ; Middle Aged ; *Tomography/methods ; Disease Progression ; Aged ; Vital Capacity/physiology ; Respiratory Function Tests/methods ; *Lung Diseases/etiology/diagnostic imaging/physiopathology ; Longitudinal Studies ; Adult ; *Lung/physiopathology/diagnostic imaging ; }, abstract = {Objective: We compared thoracic electrical impedance tomography (EIT) with slow vital capacity (SVC) to determine if EIT could monitor pulmonary function in ALS patients longitudinally. Methods: Of 32 ALS patients and 32 age- and sex-matched healthy controls (HCs) initially enrolled in the Pulmonary Function via Impedance Tomography (PuFIT) study, 22 ALS and 20 HCs returned for a follow-up visit ∼3.9 months later. All participants had thoracic EIT measurements performed simultaneously with standard SVC in upright and supine positions at both visits. EIT data from each measurement were summarized as a single parameter, the impedance-SVC (zSVC), representing an averaged impedance change across both lungs. We assessed alterations over time for both cohorts of participants. Results: Sufficient quality EIT and SVC data were available for 18 of the patients with ALS and 19 HCs. Over time, mean upright SVC significantly declined by 5% in the ALS group and did not change in the healthy group. Supine SVC showed no change in either group. Although mean trajectories of zSVC mirrored mean SVC trajectories in both participant cohorts, changes in zSVC in ALS patients did not reach significance, due to greater variability in the repeated measures. Conclusion: Despite strong cross-sectional correlations to SVC, EIT did not detect a decline in pulmonary function over approximately four months. Increased variability in EIT data explains the lack of sensitivity to change. Technological improvements and special care with electrode placement will be needed for EIT to reach its full potential in longitudinal assessment of pulmonary function in ALS.}, } @article {pmid39615150, year = {2025}, author = {Garbey, M and Lesport, Q and Öztosun, G and Ghodasara, V and Kaminski, HJ and Bayat, E}, title = {Improving care for amyotrophic lateral sclerosis with artificial intelligence and affective computing.}, journal = {Journal of the neurological sciences}, volume = {468}, number = {}, pages = {123328}, doi = {10.1016/j.jns.2024.123328}, pmid = {39615150}, issn = {1878-5883}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/psychology/therapy/physiopathology/diagnosis ; Male ; Female ; *Artificial Intelligence ; Middle Aged ; Aged ; *Emotions/physiology ; Natural Language Processing ; Adult ; }, abstract = {BACKGROUND: Patients with ALS often face difficulties expressing emotions due to impairments in facial expression, speech, body language, and cognitive function. This study aimed to develop non-invasive AI tools to detect and quantify emotional responsiveness in ALS patients, providing objective insights. Improved understanding of emotional responses could enhance patient-provider communication, telemedicine effectiveness, and clinical trial outcome measures.

METHODS: In this preliminary exploratory study, fourteen patients with ALS had audio recordings performed during routine clinic visits while wearing a wireless pulse oximeter. Emotion-triggering questions related to symptom progression, breathing, mobility, feeding tube, and financial burden were randomly asked. The same questions were posed in separate psychiatric evaluations. Natural language processing (NLP) was used to analyze transcriptions, topic classifications, sentiment, and emotional states, combining pulse and speech data. AI-generated reports summarized the findings.

RESULTS: Pulse alterations consistent with emotional arousal were identified, with longer consultations and positive communication reducing pulse fluctuations. Financial concerns triggered the strongest emotional response, while discussions about breathing, mobility, and feeding tube increased anxiety. AI-generated reports prioritized patient concerns and streamlined documentation for providers.

CONCLUSIONS: This study introduces a novel approach to linking pulse and speech analysis to evaluate emotional responses in ALS patients. AI and affective computing provide valuable insights into emotional responses and disease progression, with potential applications for other neurological disorders. This approach could augment clinical trial outcomes by offering a more comprehensive view of patient well-being.}, } @article {pmid39614020, year = {2025}, author = {Shi, DL and Grifone, R and Zhang, X and Li, H}, title = {Rbm24-mediated post-transcriptional regulation of skeletal and cardiac muscle development, function and regeneration.}, journal = {Journal of muscle research and cell motility}, volume = {46}, number = {1}, pages = {53-65}, pmid = {39614020}, issn = {1573-2657}, support = {23545//the French Muscular Dystrophy Association/ ; }, mesh = {*RNA-Binding Proteins/metabolism/genetics ; Humans ; Animals ; *Muscle, Skeletal/metabolism/physiology ; *Regeneration/physiology ; *Muscle Development/physiology/genetics ; *Myocardium/metabolism ; *RNA Processing, Post-Transcriptional ; Cell Differentiation ; }, abstract = {RNA-binding proteins are critically involved in the post-transcriptional control of gene expression during embryonic development and in adult life, contributing to regulating cell differentiation and maintaining tissue homeostasis. Compared to the relatively well documented functions of transcription factors, the regulatory roles of RNA-binding proteins in muscle development and function remain largely elusive. However, deficiency of many RNA-binding proteins has been associated with muscular defects, neuromuscular disorders and heart diseases, such as myotonic dystrophy, amyotrophic lateral sclerosis, and cardiomyopathy. Rbm24 is highly conserved among vertebrates and is one of the best characterized RNA-binding proteins with crucial implication in the myogenic and cardiomyogenic programs. It presents the distinctive particularity of displaying highly restricted expression in both skeletal and cardiac muscles, with changes in subcellular localization during the process of differentiation. Functional analyses using different vertebrate models have clearly demonstrated its requirement for skeletal muscle differentiation and regeneration as well as for myocardium organization and cardiac function, by regulating the expression of both common and distinct target genes in these tissues. The challenge remains to decipher the dynamic feature of post-transcriptional circuits regulated by Rbm24 during skeletal myogenesis, cardiomyogenesis, and muscle repair. This review discusses current understanding of its function in striated muscles and its possible implication in human disease, with the aim of identifying research gaps for future investigation.}, } @article {pmid39612826, year = {2025}, author = {Xu, H and Cheng, J and Leng, Q and Cao, R and Su, W and Sun, L and Xue, F and Han, Y and Wu, R}, title = {Characterization of acetolactate synthase genes and resistance mechanisms of multiple herbicide resistant Lolium multiflorum.}, journal = {Plant physiology and biochemistry : PPB}, volume = {219}, number = {}, pages = {109324}, doi = {10.1016/j.plaphy.2024.109324}, pmid = {39612826}, issn = {1873-2690}, mesh = {*Acetolactate Synthase/genetics/metabolism ; *Herbicide Resistance/genetics ; *Lolium/genetics/enzymology/drug effects ; *Herbicides/pharmacology ; *Plant Proteins/genetics/metabolism ; Imidazoles/pharmacology ; Genes, Plant ; Mutation ; }, abstract = {Combining imidazolinone-tolerant wheat with imazamox presents an effective solution to combat weed resistance. However, Lolium multiflorum, a troublesome resistant weed infesting wheat fields, may have developed resistance to imazamox, and the potential resistance mechanisms are intriguing. In this study, we explored the susceptibility of L. multiflorum to imazamox and investigated the resistance mechanisms, including the contribution of the target enzyme acetolactate synthase (ALS) to resistance and the presence of non-target-site resistance (NTSR). Eight L. multiflorum populations suspected of being resistant to imazamox were collected, and six populations exhibited resistance, ranging from 2.45-fold to 16.32-fold. The LmALS1 gene from susceptible population D3 plants and multiple copies of the LmALS gene (LmALS1, LmALS2, LmALS2α, LmALS3, LmALS3α, LmALS3β) from resistant populations D5 and D8 plants were separately amplified. Two mutations (Pro/Gln197 to Thr, Trp574 to Leu) were found in LmALS1 in the resistant populations. Compared to D3, LmALS1 was overexpressed in D5 but not in D8. The presence of LmALS1 mutants (LmALS1-Thr197 and LmALS1- Leu574), along with LmALS2, LmALS3, and their subunits, contribute to the resistance phenotype by increasing bonding energies, weakening hydrogen bonds, or decreasing protein binding pocket volumes and surface area. Additionally, D5 and D8 populations exhibited multiple resistance (>40-fold) to three other ALS inhibitors: pyroxsulam, flucarbazone-sodium, and mesosulfuron-methyl. Pre-treatment with malathion and 4-chloro-7-nitrobenzoxadiazole (cytochrome P450 monooxygenase and glutathione S-transferase inhibitors respectively) reversed the resistance of the D8 population and partially reversed the resistance of the D5 population to imazamox. This study characterizes ALS genes and extends our knowledge into the ALS resistance mechanisms involved in L. multiflorum. It also deepens our understanding of the complex diversification resistance mechanisms, thereby facilitating advances in weed resistance management strategies in wheat fields.}, } @article {pmid39612643, year = {2024}, author = {Egorov, VV and Grudinina, NA and Polyakov, DS and Zabrodskaya, YA and Gavrilova, NV and Shavlovsky, MM}, title = {Spontaneous formation of different forms of alpha-synuclein fibrils from a recombinant protein.}, journal = {Biochemical and biophysical research communications}, volume = {741}, number = {}, pages = {151068}, doi = {10.1016/j.bbrc.2024.151068}, pmid = {39612643}, issn = {1090-2104}, mesh = {*alpha-Synuclein/metabolism/chemistry ; *Recombinant Proteins/chemistry/metabolism/genetics ; Humans ; *Amyloid/chemistry/metabolism ; Protein Processing, Post-Translational ; Protein Conformation ; }, abstract = {Alpha-synuclein is a protein, the conformational changes of which lead to the development of such socially significant diseases as Parkinson's disease and amyotrophic lateral sclerosis. The methods for differential diagnostics of these diseases based on the use of alpha-synuclein in a non-native conformation obtained from patients as a seed for inducing fibrillogenesis and studying the morphology of the resulting amyloid-like fibrils were described in a number of studies. The authors associate such properties of the seed with the presence of post-translational modifications in the protein obtained from patients. At the same time, the production of fibrils differing in morphology from recombinant alpha-synuclein under various conditions of fibrillogenesis is also described. In this work, we show that the formation of morphologically distinct fibril types from recombinant alpha-synuclein lacking post-translational modifications is possible under the same conditions, and that spontaneously arising different fibril types, when used as a seed for fibrillogenesis, lead to the formation of recombinant protein fibrils morphological similar to the parental seed. The results of the work can be used both in studying the fundamental mechanisms of conformation transfer and in developing test systems for synucleinopathies.}, } @article {pmid39611550, year = {2025}, author = {Veyrat-Durebex, C and Osman, S and Al Ojaimi, Y and Gosset, P and Dupuy, C and Lefevre, A and Emond, P and Vourc'h, P and Corcia, P and Mereghetti, L and Kempf, F and Raoul, C and Blasco, H}, title = {Gut metabolomic and microbiota analyses in ALS mice reveal specific metabolites despite the absence of significant gut dysbiosis.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {26}, number = {3-4}, pages = {368-374}, doi = {10.1080/21678421.2024.2433578}, pmid = {39611550}, issn = {2167-9223}, mesh = {Animals ; *Amyotrophic Lateral Sclerosis/metabolism/genetics/microbiology ; *Gastrointestinal Microbiome/physiology ; Mice ; *Dysbiosis/metabolism ; Disease Models, Animal ; Metabolomics ; Feces/microbiology ; Mice, Transgenic ; Male ; Female ; Superoxide Dismutase-1/genetics ; Superoxide Dismutase/genetics ; }, abstract = {OBJECTIVE: Over the past years, interest in the role of gut microbiota in neurodegenerative diseases has emerged. Despite numerous publications over the past decade, both in human and pre-clinical studies, there is no clear consensus on the microbiota's role or involvement in ALS. Few studies on mouse models of ALS highlighted a correlation between specific bacteria species and the prognostic or severity of the disease. Still these results lack reproducibility and remain controverted. In this article we present a study of fecal microbiota in the SOD1[G93A] mouse model associated with a metabolomic analysis of cecum content, compared to controls.

METHODS: Intestinal metabolomic profile and fecal microbiota were assessed in two cohorts of SOD[G93A] mice compared to wildtype controls at the terminal stage of the ALS disease.

RESULTS: Results showed a significant difference in metabolomic profile in SOD1[G93A] mice compared to controls but without a marked change in composition and diversity of fecal microbiota. Nevertheless, we observed an increase of Lachnospiraceae family, which are butyrate-producer bacteria, in SOD1[G93A] mice. Moreover, some metabolites with significantly different intestinal concentrations are partially produced and linked with intestinal bacteria, such as riboflavin, hippurate, and N-acetylputrescine, leaving us convinced of the interest in looking further into the role of the microbiota in ALS.

CONCLUSIONS: Despite an alteration of the intestinal metabolome in SOD1[G93A] mice, microbiota data did not show significant changes, underlying the need for further research.}, } @article {pmid39611310, year = {2025}, author = {Diaz, F and Thornton, JS and Wastling, SS and Asaab, A and Morrow, JM and Zafeiropoulos, N and Bresee, C and Allred, P and Avalos, P and Lewis, RA and Baloh, RH and Svendsen, CN}, title = {Longitudinal Quantitative MRI Provides Responsive Outcome Measures for Early and Late Muscle Changes in ALS.}, journal = {Muscle & nerve}, volume = {71}, number = {2}, pages = {171-182}, doi = {10.1002/mus.28306}, pmid = {39611310}, issn = {1097-4598}, support = {CLIN2-09284//This study was supported with funding from The California Institute of Regenerative Medicine./ ; }, mesh = {Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; *Amyotrophic Lateral Sclerosis/diagnostic imaging/physiopathology ; *Disease Progression ; Longitudinal Studies ; *Magnetic Resonance Imaging ; Muscle Strength/physiology ; *Muscle, Skeletal/diagnostic imaging/physiopathology ; Outcome Assessment, Health Care ; Clinical Trials, Phase I as Topic ; }, abstract = {INTRODUCTION/AIMS: Studies have demonstrated the potential of muscle MRIs to measure disease progression in ALS. However, the responsiveness and utility of quantitative muscle MRIs in an ALS clinical trial remain unknown. This study aimed to determine the responsiveness of quantitative muscle MRIs to measure disease progression in ALS.

METHODS: Longitudinal quantitative muscle MRIs were obtained in an ALS study that delivered human neural progenitor cells to the spinal cord (NCT02943850). Participants underwent MRIs at baseline, 1, 3, 6, 9, and 12 months. MRI measures included fat fraction (ff), water T2 (T 2m), cross-sectional area (CSA), and remaining muscle area (RMA). Non-MRI measures included strength via Accurate Test of Limb Isometric Strength (ATLIS) and the ALSFRS-R. Standardized response means (SRM) were calculated at 1, 3, 6, and 12 months.

RESULTS: Significant increases in muscle FF and decreases in CSA and RMA were seen as early as 1 month from baseline. At 6 months, the most responsive measures were muscle FF (SRMthigh = 1.85, SRMcalf = 1.39), T 2m (SRMthigh = 1.2, SRMcalf = 1.71), CSA (SRMthigh = -1.58, SRMcalf = -1.14), RMA (SRMthigh = -1.77, SRMcalf = -1.28), and strength tested via ATLIS (SRMknee extension = -1.79, SRMknee flexion = -1.3). The ALSFRS-R was the least responsive at 6 months (SRM = -0.85). Muscle FF and T 2m correlated with ALSFRS-R leg subscores and MRI measures demonstrated varying degrees of correlation with strength.

DISCUSSION: High responsiveness and low variability make quantitative muscle MRI a novel and complementary outcome measure for ALS clinical trials.}, } @article {pmid39611137, year = {2024}, author = {Valančius, D and Burnytė, B and Masaitienė, R and Morkūnienė, A and Klimašauskienė, A}, title = {Rapidly Progressing and Early-Onset Forms of Amyotrophic Lateral Sclerosis Caused by a Novel SOD1 Variant in a Lithuanian Family.}, journal = {Neurology. Genetics}, volume = {10}, number = {6}, pages = {e200217}, pmid = {39611137}, issn = {2376-7839}, abstract = {OBJECTIVES: To describe a novel familial variant of superoxide dismutase 1 (SOD1)-associated amyotrophic lateral sclerosis (ALS) in a Lithuanian family, highlighting its variable progression and implications for treatment inclusion criteria.

METHODS: This study presents the clinical and genetic findings of a family with the novel SOD1 variant, including one member diagnosed with early-onset ALS (onset <40 years) and one with a particularly rapidly progressing course of ALS.

RESULTS: The SOD1 variant NM_000454.5:c.446T>C, NP_000445.1:p.(Val149Ala) was identified in affected family members and 4 asymptomatic members aged 32-56 years. We present detailed disease course of the affected family members obtained during follow-up. Clinically, this variant is associated with variable disease progression, with the time from symptom onset to death ranging from 5 to 77 months.

DISCUSSION: The novel SOD1 variant p.Val149Ala in this Lithuanian family causes ALS of variable onset and course, including a case of early-onset ALS and one case of rapidly progressing ALS, necessitating recognition by the scientific community and development of tailored therapeutic approaches.}, } @article {pmid39610104, year = {2025}, author = {Bar Avi, O and Perlson, E}, title = {Navigating the pathways: TAR-DNA-binding-protein-43 aggregation, axonal transport, and local synthesis in amyotrophic lateral sclerosis pathology.}, journal = {Neural regeneration research}, volume = {20}, number = {10}, pages = {2921-2922}, pmid = {39610104}, issn = {1673-5374}, } @article {pmid39608855, year = {2024}, author = {Budworth, L and Wilson, B and Sutton-Klein, J and Basu, S and O'Keeffe, C and Mason, SM and Ang, A and Anne-Wilson, S and Reynard, K and Croft, S and Shah, AD and Bank, S and Conner, M and Lawton, R}, title = {Is emergency doctors' tolerance of clinical uncertainty on a novel measure associated with doctor well-being, healthcare resource use and patient outcomes?.}, journal = {Emergency medicine journal : EMJ}, volume = {42}, number = {1}, pages = {}, pmid = {39608855}, issn = {1472-0213}, abstract = {INTRODUCTION: Emergency doctors routinely face uncertainty-they work with limited patient information, under tight time constraints and receive minimal post-discharge feedback. While higher uncertainty tolerance (UT) among staff is linked with reduced resource use and improved well-being in various specialties, its impact in emergency settings is underexplored. We aimed to develop a UT measure and assess associations with doctor-related factors (eg, experience), patient outcomes (eg, reattendance) and resource use (eg, episode costs).

METHODS: From May 2021 to February 2022, emergency doctors (specialty trainee 3 and above) from five Yorkshire (UK) departments completed an online questionnaire. This included a novel UT measure-an adapted Physicians' Reaction to Uncertainty scale collaboratively modified within our team according to Hillen et al's (2017) UT model. The questionnaire also included well-being-related measures (eg, Brief Resilience Scale) and assessed factors like doctors' seniority. Patient encounters involving prespecified 'uncertainty-inducing' problems (eg, headache) were analysed. Multilevel regression explored associations between doctor-level factors, resource use and patient outcomes.

RESULTS: 39 doctors were matched with 384 patients. The UT measure demonstrated high reliability (Cronbach's α=0.92) and higher UT was significantly associated with better psychological well-being including greater resilience (Pearson's r=0.56; 95% CI=0.30 to 0.74) and lower burnout (eg, Cohen's d=-2.98; -4.62 to -1.33; mean UT difference for 'no' vs 'moderate/high' burnout). UT was not significantly associated with resource use (eg, episode costs: β=-0.07; -0.32 to 0.18) or patient outcomes including 30-day readmission (eg, OR=0.82; 0.28 to 2.35).

CONCLUSIONS: We developed a reliable UT measure for emergency medicine. While higher UT was linked to doctor well-being, its impact on resource use and patient outcomes remains unclear. Further measure validation and additional research including intervention trials are necessary to confirm these findings and explore the implications of UT in emergency practice.}, } @article {pmid39608699, year = {2025}, author = {Kale, MB and Wankhede, NL and Bishoyi, AK and Ballal, S and Kalia, R and Arya, R and Kumar, S and Khalid, M and Gulati, M and Umare, M and Taksande, BG and Upaganlawar, AB and Umekar, MJ and Kopalli, SR and Fareed, M and Koppula, S}, title = {Emerging biophysical techniques for probing synaptic transmission in neurodegenerative disorders.}, journal = {Neuroscience}, volume = {565}, number = {}, pages = {63-79}, doi = {10.1016/j.neuroscience.2024.11.055}, pmid = {39608699}, issn = {1873-7544}, mesh = {Humans ; *Neurodegenerative Diseases/metabolism/pathology/physiopathology ; *Synaptic Transmission/physiology ; Animals ; Synapses/metabolism/pathology/physiology ; }, abstract = {Plethora of research has shed light on the critical role of synaptic dysfunction in various neurodegenerative disorders (NDDs), including Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD). Synapses, the fundamental units for neural communication in the brain, are highly vulnerable to pathological conditions and are central to the progression of neurological diseases. The presynaptic terminal, a key component of synapses responsible for neurotransmitter release and synaptic communication, undergoes structural and functional alterations in these disorders. Understanding synaptic transmission abnormalities is crucial for unravelling the pathophysiological mechanisms underlying neurodegeneration. In the quest to probe synaptic transmission in NDDs, emerging biophysical techniques play a pivotal role. These advanced methods offer insights into the structural and functional changes occurring at nerve terminals in conditions like AD, PD, HD & ALS. By investigating synaptic plasticity and alterations in neurotransmitter release dynamics, researchers can uncover valuable information about disease progression and potential therapeutic targets. The review articles highlighted provide a comprehensive overview of how synaptic vulnerability and pathology are shared mechanisms across a spectrum of neurological disorders. In major neurodegenerative diseases, synaptic dysfunction is a common thread linking these conditions. The intricate molecular machinery involved in neurotransmitter release, synaptic vesicle dynamics, and presynaptic protein regulation are key areas of focus for understanding synaptic alterations in neurodegenerative diseases.}, } @article {pmid39608571, year = {2025}, author = {Diggins, L and Ross, D and Bhanot, S and Corallo, R and Daley, R and Patel, K and Lewis, O and Donahue, S and Thaddeus, J and Hiers, L and Syed, C and Eagerton, D and Mohanty, BK}, title = {CD spectra reveal the state of G-quadruplexes and i-motifs in repeated and other DNA sequences.}, journal = {Biophysical reports}, volume = {5}, number = {1}, pages = {100187}, pmid = {39608571}, issn = {2667-0747}, mesh = {*G-Quadruplexes ; *Circular Dichroism ; *DNA/chemistry/genetics ; Hydrogen-Ion Concentration ; Humans ; *Nucleotide Motifs ; Base Sequence ; *Repetitive Sequences, Nucleic Acid ; Temperature ; }, abstract = {The B-DNA of the genome contains numerous sequences that can form various noncanonical structures including G-quadruplex (G4), formed by two or more stacks of four guanine residues in a plane, and intercalating motif (i-motif [iM]) formed by alternately arranged C-C[+] pairs. One of the easy yet sensitive methods to study G4s and iMs is circular dichroism (CD) spectroscopy, which generates characteristic G4 and iM peaks. We have analyzed and compared the effects of various environmental factors including pH, buffer composition, temperature, flanking sequences, complimentary DNA strands, and single-stranded DNA binding protein (SSB) on the CD patterns of G4s and iMs generated by two groups of DNA molecules, one containing tandem repeats of GGGGCC and CCCCGG from the C9ORF72 gene associated with amyotrophic lateral sclerosis and frontotemporal dementia, and the second containing polyG/polyC clusters from oncogene promoter-proximal regions without such tandem repeats. Changes in pH caused drastic changes in CCCCGG-iM and GGGGCC-G4 and the changes were dependent on repeat numbers and G-C basepairing. In contrast, with the DNA sequences from the promoter-proximal regions of oncogenes, iMs disassembled upon pH changes with the peak slowly shifting to lower wavelength but the G4s did not show significant change. Complementary DNA strands and flanking DNA sequences also regulate G4 and iM formation. The SSB disassembled both G4s and iMs formed by almost all sequences suggesting an in vivo role for SSBs in the disassembly of G4s and iMs during DNA replication and other DNA transactions.}, } @article {pmid39606446, year = {2024}, author = {Du, M and Akerman, SC and Fare, CM and Ruan, L and Vidensky, S and Mamedova, L and Lee, J and Rothstein, JD}, title = {Divergent and Convergent TMEM106B Pathology in Murine Models of Neurodegeneration and Human Disease.}, journal = {Research square}, volume = {}, number = {}, pages = {}, pmid = {39606446}, issn = {2693-5015}, support = {P50 AG005146/AG/NIA NIH HHS/United States ; R35 NS132179/NS/NINDS NIH HHS/United States ; }, abstract = {TMEM106B is a lysosomal/late endosome protein that is a potent genetic modifier of multiple neurodegenerative diseases as well as general aging. Recently, TMEM106B was shown to form insoluble aggregates in postmortem human brain tissue, drawing attention to TMEM106B pathology and the potential role of TMEM106B aggregation in disease. In the context of neurodegenerative diseases, TMEM106B has been studied in vivo using animal models of neurodegeneration, but these studies rely on overexpression or knockdown approaches. To date, endogenous TMEM106B pathology and its relationship to known canonical pathology in animal models has not been reported. Here, we analyze histological patterns of TMEM106B in murine models of C9ORF72-related amyotrophic lateral sclerosis and frontotemporal dementia (C9-ALS/FTD), SOD1-related ALS, and tauopathy and compare these to postmortem human tissue from patients with C9-ALS/FTD, Alzheimer's disease (AD), and AD with limbic-predominant age-related TDP-43 encephalopathy (AD/LATE). We show that there are significant differences between TMEM106B pathology in mouse models and human patient tissue. Importantly, we also identified convergent evidence from both murine models and human patients that links TMEM106B pathology to TDP-43 nuclear clearance specifically in C9-ALS. Similarly, we find a relationship at the cellular level between TMEM106B pathology and phosphorylated Tau burden in Alzheimer's disease. By characterizing endogenous TMEM106B pathology in both mice and human postmortem tissue, our work reveals considerations that must be taken into account when analyzing data from in vivo mouse studies and elucidates new insights supporting the involvement of TMEM106B in the pathogenesis and progression of multiple neurodegenerative diseases.}, } @article {pmid39606178, year = {2024}, author = {Tröger, J and Dörr, F and Schwed, L and Linz, N and König, A and Thies, T and Barbe, MT and Orozco-Arroyave, JR and Rusz, J}, title = {Corrigendum: An automatic measure for speech intelligibility in dysarthrias-validation across multiple languages and neurological disorders.}, journal = {Frontiers in digital health}, volume = {6}, number = {}, pages = {1488178}, doi = {10.3389/fdgth.2024.1488178}, pmid = {39606178}, issn = {2673-253X}, abstract = {[This corrects the article DOI: 10.3389/fdgth.2024.1440986.].}, } @article {pmid39605661, year = {2024}, author = {Zimyanin, V and Dash, BP and Großmann, D and Simolka, T and Glaß, H and Verma, R and Khatri, V and Deppmann, C and Zunder, E and Redemann, S and Hermann, A}, title = {Axonal transcriptome reveals upregulation of PLK1 as a protective mechanism in response to increased DNA damage in FUS [P525L] spinal motor neurons.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2024.11.20.624439}, pmid = {39605661}, issn = {2692-8205}, support = {R01 NS091617/NS/NINDS NIH HHS/United States ; }, abstract = {Mutations in the gene FUSED IN SARCOMA (FUS) are among the most frequently occurring genetic forms of amyotrophic lateral sclerosis (ALS). Early pathogenesis of FUS -ALS involves impaired DNA damage response and axonal degeneration. However, it is still poorly understood how these gene mutations lead to selective spinal motor neuron (MN) degeneration and how nuclear and axonal phenotypes are linked. To specifically address this, we applied a compartment specific RNA-sequencing approach using microfluidic chambers to generate axonal as well as somatodendritic compartment-specific profiles from isogenic induced pluripotent stem cells (iPSCs)-derived MNs. We demonstrate high purity of axonal and soma fractions and show that the axonal transcriptome is unique and distinct from that of somas including significantly fewer number of transcripts. Functional enrichment analysis revealed that differentially expressed genes (DEGs) in axons were mainly enriched in key pathways like RNA metabolism and DNA damage, complementing our knowledge of early phenotypes in ALS pathogenesis and known functions of FUS. In addition, we demonstrate a strong enrichment for cell cycle associated genes including significant upregulation of polo-like kinase 1 (PLK1) in FUS [P525L] mutant MNs. PLK1 was increased upon DNA damage induction and PLK1 inhibition further increased the number of DNA damage foci in etoposide-treated cells, an effect that was diminished in case of FUS mutant MNs. In contrast, inhibition of PLK1 increased late apoptotic or necrosis-induced neuronal cell death in mutant neurons. Taken together, our findings provide insights into compartment-specific transcriptomics in human FUS -ALS MNs and we propose that specific upregulation of PLK1 might represent an early event in the pathogenesis of ALS, possibly modulating DNA damage response and other associated pathways.}, } @article {pmid39605556, year = {2024}, author = {Singer-Clark, T and Hou, X and Card, NS and Wairagkar, M and Iacobacci, C and Peracha, H and Hochberg, LR and Stavisky, SD and Brandman, DM}, title = {Speech motor cortex enables BCI cursor control and click.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {39605556}, issn = {2692-8205}, support = {DP2 DC021055/DC/NIDCD NIH HHS/United States ; }, abstract = {Decoding neural activity from ventral (speech) motor cortex is known to enable high-performance speech brain-computer interface (BCI) control. It was previously unknown whether this brain area could also enable computer control via neural cursor and click, as is typically associated with dorsal (arm and hand) motor cortex. We recruited a clinical trial participant with ALS and implanted intracortical microelectrode arrays in ventral precentral gyrus (vPCG), which the participant used to operate a speech BCI in a prior study. We developed a cursor BCI driven by the participant's vPCG neural activity, and evaluated performance on a series of target selection tasks. The reported vPCG cursor BCI enabled rapidly-calibrating (40 seconds), accurate (2.90 bits per second) cursor control and click. The participant also used the BCI to control his own personal computer independently. These results suggest that placing electrodes in vPCG to optimize for speech decoding may also be a viable strategy for building a multi-modal BCI which enables both speech-based communication and computer control via cursor and click.}, } @article {pmid39605399, year = {2024}, author = {Tuddenham, JF and Fujita, M and Khairallah, A and Harbison, C and Flowers, XE and Coronas-Samano, G and Maniatis, S and Daly, A and Schneider, JA and Teich, AF and Vonsattel, JPG and Sims, PA and Elyaman, W and Bradshaw, EM and Phatnani, H and Shneider, N and Bennett, DA and De Jager, PL and Przedborski, S and Menon, V and Olah, M}, title = {Single-cell transcriptomic landscape of the neuroimmune compartment in amyotrophic lateral sclerosis brain and spinal cord.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2024.11.12.623183}, pmid = {39605399}, issn = {2692-8205}, support = {P30 AG072975/AG/NIA NIH HHS/United States ; R25 MH129256/MH/NIMH NIH HHS/United States ; }, abstract = {Development of therapeutic approaches that target specific microglia responses in amyotrophic lateral sclerosis (ALS) is crucial due to the involvement of microglia in ALS progression. Our study identifies the predominant microglia subset in human ALS primary motor cortex and spinal cord as an undifferentiated phenotype with dysregulated respiratory electron transport. Moreover, we find that the interferon response microglia subset is enriched in donors with aggressive disease progression, while a previously described potentially protective microglia phenotype is depleted in ALS. Additionally, we observe an enrichment of non-microglial immune cell, mainly NK/T cells, in ALS central nervous system, primarily in the spinal cord. These findings pave the way for the development of microglia subset-specific therapeutic interventions to slow or even stop ALS progression.}, } @article {pmid39605053, year = {2024}, author = {Horiuchi, M and Watanabe, S and Komine, O and Takahashi, E and Kaneko, K and Itohara, S and Shimada, M and Ogi, T and Yamanaka, K}, title = {ALS-linked mutant TDP-43 in oligodendrocytes induces oligodendrocyte damage and exacerbates motor dysfunction in mice.}, journal = {Acta neuropathologica communications}, volume = {12}, number = {1}, pages = {184}, pmid = {39605053}, issn = {2051-5960}, support = {JP23K06826//Japan Society for the Promotion of Science/ ; JP19KK0214//Japan Society for the Promotion of Science/ ; JP22H00467//Japan Society for the Promotion of Science/ ; JP22ek0109426//Japan Agency for Medical Research and Development/ ; JP24wm0425014//Japan Agency for Medical Research and Development/ ; JP24wm0625301//Japan Agency for Medical Research and Development/ ; }, mesh = {Animals ; *Oligodendroglia/metabolism/pathology ; *DNA-Binding Proteins/metabolism/genetics ; *Mice, Transgenic ; Mice ; *Amyotrophic Lateral Sclerosis/genetics/pathology/metabolism ; Mutation ; Spinal Cord/metabolism/pathology ; Mice, Inbred C57BL ; }, abstract = {Nuclear clearance and cytoplasmic aggregation of TAR DNA-binding protein of 43 kDa (TDP-43) are pathological hallmarks of amyotrophic lateral sclerosis (ALS) and its pathogenic mechanism is mediated by both loss-of-function and gain-of-toxicity of TDP-43. However, the role of TDP-43 gain-of-toxicity in oligodendrocytes remains unclear. To investigate the impact of excess TDP-43 on oligodendrocytes, we established transgenic mice overexpressing the ALS-linked mutant TDP-43[M337V] in oligodendrocytes through crossbreeding with Mbp-Cre mice. Two-step crossbreeding of floxed TDP-43[M337V] and Mbp-Cre mice resulted in the heterozygous low-level systemic expression of TDP-43[M337V] with (Cre-positive) or without (Cre-negative) oligodendrocyte-specific overexpression of TDP-43[M337V]. Although Cre-negative mice also exhibit subtle motor dysfunction, TDP-43[M337V] overexpression in oligodendrocytes aggravated clasping signs and gait disturbance accompanied by myelin pallor in the corpus callosum and white matter of the lumbar spinal cord in Cre-positive mice. RNA sequencing analysis of oligodendrocyte lineage cells isolated from whole brains of 12-month-old transgenic mice revealed downregulation of myelinating oligodendrocyte marker genes and cholesterol-related genes crucial for myelination, along with marked upregulation of apoptotic pathway genes. Immunofluorescence staining showed cleaved caspase 3-positive apoptotic oligodendrocytes surrounded by activated microglia and astrocytes in aged transgenic mice. Collectively, our findings demonstrate that an excess amount of ALS-linked mutant TDP-43 expression in oligodendrocytes exacerbates motor dysfunction in mice, likely through oligodendrocyte dysfunction and neuroinflammation. Therefore, targeting oligodendrocyte protection, particularly through ameliorating TDP-43 pathology, could represent a potential therapeutic approach for ALS.}, } @article {pmid39604641, year = {2025}, author = {Mi, Y and Zhang, P and Hou, X and Ding, Y and Wang, Y and Du, H and Deng, M}, title = {A rare genetic variant in APEX1 is associated with familial amyotrophic lateral sclerosis with slow progression.}, journal = {Acta neurologica Belgica}, volume = {125}, number = {1}, pages = {191-203}, pmid = {39604641}, issn = {2240-2993}, support = {No. 82273915//National Natural Science Foundation of China/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics ; Male ; Female ; Middle Aged ; *DNA-(Apurinic or Apyrimidinic Site) Lyase/genetics ; Disease Progression ; Adult ; Aged ; Pedigree ; Mutation, Missense ; Genetic Variation/genetics ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by loss of motor neurons and progressive muscle weakness. We aimed to identify the pathogenic genetic variants in familial ALS (fALS) pedigrees and to elucidate their impact on the disease phenotype. Through the analysis of whole-genome sequencing data of 34 fALS probands that screened negative for mutations in the most common ALS-causing genes, we identified a rare missense variant in APEX1 (NM_001641.4: c.22G > A, p.Gly8Arg) associated with ALS in one pedigree. Fluorescence microscopy images using green fluorescent protein (GFP)-fusion proteins suggested that this amino acid substitution could cause an impairment in nuclear localization of the protein. We described the clinical characteristics of this cohort analyzed and found that patients carrying this variant exhibit lower motor neuron onset and prolonged survival. The relation between APEX1 and ALS occurrence has been elusive despite evidence of a neuroprotective role for the gene. This study provides evidence linking an APEX1 variant with fALS and information on the distinct clinical manifestation. This study contributes to the understanding of the genetic basis of ALS, as well as a potential mechanism leading to loss of neurons, highlighting possible opportunities of targeted treatment harnessing the DNA repair process or ameliorating the oxidative stress.}, } @article {pmid39603574, year = {2024}, author = {Wen, J and Li, Y and Qin, Y and Yan, L and Zhang, K and Li, A and Wang, Z and Yu, F and Lai, J and Yang, W and Liu, YU and Qin, D and Su, H}, title = {Lycorine protects motor neurons against TDP-43 proteinopathy-induced degeneration in cross-species models with amyotrophic lateral sclerosis.}, journal = {Pharmacological research}, volume = {210}, number = {}, pages = {107518}, doi = {10.1016/j.phrs.2024.107518}, pmid = {39603574}, issn = {1096-1186}, mesh = {Animals ; *Amyotrophic Lateral Sclerosis/drug therapy/metabolism/pathology ; *Phenanthridines/pharmacology/therapeutic use ; *Amaryllidaceae Alkaloids/pharmacology/therapeutic use ; *Caenorhabditis elegans/drug effects/metabolism ; *Motor Neurons/drug effects/pathology/metabolism ; Humans ; *Disease Models, Animal ; TDP-43 Proteinopathies/drug therapy/metabolism/pathology ; DNA-Binding Proteins/metabolism/genetics ; Neuroprotective Agents/pharmacology/therapeutic use ; Mice ; Mice, Transgenic ; }, abstract = {Aggregation of TAR-DNA binding protein-43 (TDP-43) is a pathological feature present in nearly 97 % cases of amyotrophic lateral sclerosis (ALS), making it an attractive target for pathogenic studies and drug screening. Here, we have performed a high-throughput screening of 1500 compounds from a natural product library and identified that lycorine, a naturally occurring alkaloid, significantly decreases the level of TDP-43[A315T] in a cellular model. We further demonstrate that lycorine reduces the level of TDP-43[A315T] both through inhibiting its synthesis and by promoting its degradation by the ubiquitin-proteasome system (UPS). Importantly, treatment with lycorine significantly attenuates TDP-43 proteinopathy and improves functional recovery in TDP-43[A315T]-expressing Caenorhabditis elegans and mouse models. These findings suggest that lycorine is a promising lead compound that has therapeutic potential for ALS.}, } @article {pmid39603486, year = {2025}, author = {Krus, KL and Benitez, AM and Strickland, A and Milbrandt, J and Bloom, AJ and DiAntonio, A}, title = {Two cardinal features of ALS, reduced STMN2 and pathogenic TDP-43, synergize to accelerate motor decline in mice.}, journal = {Experimental neurology}, volume = {384}, number = {}, pages = {115068}, doi = {10.1016/j.expneurol.2024.115068}, pmid = {39603486}, issn = {1090-2430}, support = {R01 NS087632/NS/NINDS NIH HHS/United States ; R01 NS119812/NS/NINDS NIH HHS/United States ; RF1 AG013730/AG/NIA NIH HHS/United States ; }, mesh = {Animals ; Mice ; *Stathmin/genetics/metabolism ; *Amyotrophic Lateral Sclerosis/genetics/pathology/metabolism ; *DNA-Binding Proteins/genetics/metabolism ; Mice, Transgenic ; Mice, Inbred C57BL ; Male ; }, abstract = {Pathological TDP-43 loss from the nucleus and cytoplasmic aggregation occurs in almost all cases of ALS and half of frontotemporal dementia patients. Stathmin2 (Stmn2) is a key target of TDP-43 regulation and aberrantly spliced Stmn2 mRNA is found in patients with ALS, frontotemporal dementia, and Alzheimer's Disease. STMN2 participates in the axon injury response and its depletion in vivo partially replicates ALS-like symptoms including progressive motor deficits and distal NMJ denervation. The interaction between STMN2 loss and TDP-43 dysfunction has not been studied in mice because TDP-43 regulates human but not murine Stmn2 splicing. Therefore, we generated trans-heterozygous mice that lack one functional copy of Stmn2 and express one mutant TDP-43[Q331K] knock-in allele to investigate whether reduced STMN2 function exacerbates TDP-43-dependent pathology. Indeed, we observe synergy between these two alleles, resulting in an early onset, progressive motor deficit. Surprisingly, this behavioral defect is not accompanied by detectable neuropathology in the brain, spinal cord, peripheral nerves or at neuromuscular junctions (NMJs). However, the trans-heterozygous mice exhibit abnormal mitochondrial morphology in their distal axons and NMJs. As both STMN2 and TDP-43 affect mitochondrial dynamics, and neuronal mitochondrial dysfunction is a cardinal feature of many neurodegenerative diseases, this abnormality likely contributes to the observed motor deficit. These findings demonstrate that partial loss of STMN2 significantly exacerbates TDP-43-associated phenotypes, suggesting that STMN2 restoration could ameliorate TDP-43 related disease before the onset of degeneration.}, } @article {pmid39602529, year = {2024}, author = {Jin, S and Tian, Y and Hacker, J and Chen, X and Bertolio, M and Reynolds, C and Jarvis, R and Hu, J and Promes, V and Halim, D and Gao, FB and Yang, Y}, title = {Inflammatory cytokines disrupt astrocyte exosomal HepaCAM-mediated protection against neuronal excitotoxicity in the SOD1G93A ALS model.}, journal = {Science advances}, volume = {10}, number = {48}, pages = {eadq3350}, pmid = {39602529}, issn = {2375-2548}, support = {R37 NS057553/NS/NINDS NIH HHS/United States ; R01 NS101986/NS/NINDS NIH HHS/United States ; R01 AG078728/AG/NIA NIH HHS/United States ; R01 NS118747/NS/NINDS NIH HHS/United States ; R01 NS125490/NS/NINDS NIH HHS/United States ; }, mesh = {*Amyotrophic Lateral Sclerosis/metabolism/genetics/pathology ; Animals ; *Astrocytes/metabolism ; *Exosomes/metabolism ; Mice ; Humans ; *Cytokines/metabolism ; *Disease Models, Animal ; *Superoxide Dismutase-1/metabolism/genetics ; *Motor Neurons/metabolism/pathology ; *Mice, Transgenic ; Induced Pluripotent Stem Cells/metabolism ; Neurons/metabolism ; }, abstract = {Astrocyte secreted signals substantially affect disease pathology in neurodegenerative diseases. It remains little understood about how proinflammatory cytokines, such as interleukin-1α/tumor necrosis factor-α/C1q (ITC), often elevated in neurodegenerative diseases, alter astrocyte-secreted signals and their effects in disease pathogenesis. By selectively isolating astrocyte exosomes (A-Exo.) and employing cell type-specific exosome reporter mice, our current study showed that ITC cytokines significantly reduced A-Exo. secretion and decreased spreading of focally labeled A-Exo. in diseased SOD1G93A mice. Our results also found that A-Exo. were minimally associated with misfolded SOD1 and elicited no toxicity to mouse spinal and human iPSC-derived motor neurons. In contrast, A-Exo. were neuroprotective against excitotoxicity, which was completely diminished by ITC cytokines and partially abolished by SOD1G93A expression. Subsequent proteomic characterization of A-Exo. and genetic analysis identified that surface expression of glial-specific HepaCAM preferentially mediates A-Exo's axon protection effect. Together, our study defines a cytokine-induced loss-of-function mechanism of A-Exo. in protecting neurons from excitotoxicity in amyotrophic lateral sclerosis.}, } @article {pmid39602508, year = {2024}, author = {Lynch, EM and Pittman, S and Daw, J and Ikenaga, C and Chen, S and Dhavale, DD and Jackrel, ME and Ayala, YM and Kotzbauer, P and Ly, CV and Pestronk, A and Lloyd, TE and Weihl, CC}, title = {Seeding-competent TDP-43 persists in human patient and mouse muscle.}, journal = {Science translational medicine}, volume = {16}, number = {775}, pages = {eadp5730}, pmid = {39602508}, issn = {1946-6242}, support = {R35 GM153303/GM/NIGMS NIH HHS/United States ; R01 NS138499/NS/NINDS NIH HHS/United States ; F32 NS124841/NS/NINDS NIH HHS/United States ; K24 AR073317/AR/NIAMS NIH HHS/United States ; R01 AG031867/AG/NIA NIH HHS/United States ; }, mesh = {Animals ; Humans ; *DNA-Binding Proteins/metabolism ; Mice ; *Muscle, Skeletal/metabolism/pathology ; Amyotrophic Lateral Sclerosis/metabolism/pathology ; Myositis, Inclusion Body/metabolism/pathology ; Disease Models, Animal ; }, abstract = {TAR DNA binding protein 43 (TDP-43) is an RNA binding protein that accumulates as aggregates in the central nervous systems of some patients with neurodegenerative diseases. However, TDP-43 aggregation is also a sensitive and specific pathologic feature found in a family of degenerative muscle diseases termed inclusion body myopathy. TDP-43 aggregates from amyotrophic lateral sclerosis (ALS) and frontotemporal dementia brain lysates may serve as self-templating aggregate seeds in vitro and in vivo, supporting a prion-like spread from cell to cell. Whether a similar process occurs in patient muscle is not clear. We developed a mouse model of inducible, muscle-specific cytoplasmic localized TDP-43. These mice develop muscle weakness with robust accumulation of insoluble and phosphorylated sarcoplasmic TDP-43, leading to eosinophilic inclusions, altered proteostasis, and changes in TDP-43-related RNA processing that resolve with the removal of doxycycline. Skeletal muscle lysates from these mice also have seeding-competent TDP-43, as determined by a FRET-based biosensor, that persists for weeks upon resolution of TDP-43 aggregate pathology. Human muscle biopsies with TDP-43 pathology also contain TDP-43 aggregate seeds. Using lysates from muscle biopsies of patients with sporadic inclusion body myositis (IBM), immune-mediated necrotizing myopathy (IMNM), and ALS, we found that TDP-43 seeding capacity was specific to IBM. TDP-43 seeding capacity anticorrelated with TDP-43 aggregate and vacuole abundance. These data support that TDP-43 aggregate seeds are present in IBM skeletal muscle and represent a unique TDP-43 pathogenic species not previously appreciated in human muscle disease.}, } @article {pmid39601192, year = {2025}, author = {Sørensen, DM and Tankisi, H}, title = {Reliability of MScanFit Motor Unit Number Estimation in the Trapezius Muscle.}, journal = {Muscle & nerve}, volume = {71}, number = {2}, pages = {166-170}, doi = {10.1002/mus.28303}, pmid = {39601192}, issn = {1097-4598}, support = {//Aage & Johanne Louis-Hansens Foundation/ ; //Grosserer L. F. Foghts Foundation/ ; //Dagmar Marshalls Fond/ ; //The Jascha Foundation,/ ; //Lundbeck Foundation/ ; }, mesh = {Humans ; Male ; *Superficial Back Muscles/physiology ; Female ; Reproducibility of Results ; Adult ; *Electromyography/methods ; *Action Potentials/physiology ; Motor Neurons/physiology ; Young Adult ; Middle Aged ; Recruitment, Neurophysiological/physiology ; Amyotrophic Lateral Sclerosis/physiopathology/diagnosis ; }, abstract = {INTRODUCTION/AIMS: MScanFit motor unit number estimation (MUNE) is the most recent MUNE method which has shown promising results in extremity muscles, but it has not been applied to bulbar muscles. Bulbar muscles are particularly important in the diagnosis of amyotrophic lateral sclerosis (ALS). This study aimed to investigate the feasibility and reliability of MScanFit MUNE in the accessory nerve and trapezius muscles.

METHODS: A total of twenty healthy participants were examined twice within 1-2 weeks. We extracted the MScanFit MUNE and size parameter, and compound muscle action potential (CMAP) amplitude values. The reliability of these parameters was assessed using the intra-rater coefficient of variation (CoV), intraclass correlation coefficient (ICC), and Bland-Altman plots. We also correlated MUNE values with CMAP amplitudes using correlation coefficients.

RESULTS: Mean MUNE values (Day 1 = 132.1 and Day 2 = 137.4), CMAP amplitudes (Day 1 = 9.71 mV and Day 2 = 10.10 mV) and size parameters did not differ between the two sessions (p > 0.05). CoV showed excellent reliability for MUNE values, size parameters, and CMAP amplitudes (CoV < 7%) whereas ICCs showed moderate reliability for MUNE values (ICC = 0.619), poor to moderate reliability for size parameters (between 0.393 and 0.689), and good reliability for CMAP amplitude (ICC = 0.864) There was no correlation between MUNE values and CMAP amplitudes.

DISCUSSION: MScanFit MUNE is applicable and mostly reliable in the trapezius muscle. Further studies in patients are needed to investigate the sensitivity of MScanFit in this muscle in detecting motor unit loss, particularly in ALS.}, } @article {pmid39598374, year = {2024}, author = {Li, Y and Fu, J and Wang, H}, title = {Advancements in Targeting Ion Channels for the Treatment of Neurodegenerative Diseases.}, journal = {Pharmaceuticals (Basel, Switzerland)}, volume = {17}, number = {11}, pages = {}, pmid = {39598374}, issn = {1424-8247}, support = {2023YFF1205500//National Key Research and Development Program of China/ ; 82471465//NSFC/ ; C2024202005//Distinguished Young Scholars Science Fund of the Natural Science Foundation of Hebei Province/ ; JZX2023002//Technology Project of Hebei Education Department/ ; 22JCQNJC01110//Tianjin Applied Basic Research Project/ ; 236Z2602G, 246Z2605G, 236Z2401G//the central government guides local funds for science and technology development for Hebei Province/ ; NV20230015//The Key Laboratory of Neural and Vascular Biology, Ministry of Education/ ; }, abstract = {Ion channels are integral membrane proteins embedded in biological membranes, and they comprise specific proteins that control the flow of ion transporters in and out of cells, playing crucial roles in the biological functions of different cells. They maintain the homeostasis of water and ion metabolism by facilitating ion transport and participate in the physiological processes of neurons and glial cells by regulating signaling pathways. Neurodegenerative diseases are a group of disorders characterized by the progressive loss of neurons in the central nervous system (CNS) or peripheral nervous system (PNS). Despite significant progress in understanding the pathophysiological processes of various neurological diseases in recent years, effective treatments for mitigating the damage caused by these diseases remain inadequate. Increasing evidence suggests that ion channels are closely associated with neuroinflammation; oxidative stress; and the characteristic proteins in neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS). Therefore, studying the pathogenic mechanisms closely related to ion channels in neurodegenerative diseases can help identify more effective therapeutic targets for treating neurodegenerative diseases. Here, we discuss the progress of research on ion channels in different neurodegenerative diseases and emphasize the feasibility and potential of treating such diseases from the perspective of ion channels.}, } @article {pmid39598025, year = {2024}, author = {Vacchiano, V and Morabito, F and Bonan, L and Teodorani, L and Faini, C and Rizzo, G and Liguori, R}, title = {Reverse Split Hand as a Neurophysiological Hallmark of Spinal Muscular Atrophy.}, journal = {Journal of clinical medicine}, volume = {13}, number = {22}, pages = {}, pmid = {39598025}, issn = {2077-0383}, abstract = {Objective: Motor unit number estimation (MUNE) methods are crucial for estimating lower motor neuron loss in motor neuron diseases. The MScanFit MUNE (MScanFit) is a novel method that estimates MUNE values from compound motor action potential (CMAP) scans, demonstrating high sensitivity and reproducibility in detecting motor unit loss in amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA). In this study, we aimed to characterize the pattern of motor unit loss in the hand intrinsic muscles of SMA patients compared to ALS patients and healthy controls (HC) using MScanFit MUNE. Methods: Patients diagnosed with ALS, adult SMA patients, and HC were prospectively enrolled. MScanFit examinations were performed on the abductor pollicis brevis (APB) and abductor digiti minimi (ADM) muscles. To focus on the different patterns of motor neuron degeneration in the intrinsic hand muscles, the ratio of CMAP amplitude of APB to ADM (CMAP ratio) and the ratio of MUNE values of APB to those of the ADM muscle (MUNE ratio) were calculated. Results: The study included 46 ALS patients, 16 SMA patients, and 23 HC. MScanFit MUNE revealed distinct patterns of motor unit degeneration in SMA patients, notably more severe in the ADM than in the APB muscle, indicating a "reverse" split-hand phenomenon. Both CMAP and MUNE ratios demonstrated high diagnostic accuracy in distinguishing ALS from SMA, with the MUNE ratio performing better. Conclusions: MScanFit MUNE is a valuable tool for exploring distinct patterns of motor neuron degeneration in patients with different types of motor neuron diseases.}, } @article {pmid39596864, year = {2024}, author = {McKenna, MC and Kleinerova, J and Power, A and Garcia-Gallardo, A and Tan, EL and Bede, P}, title = {Quantitative and Computational Spinal Imaging in Neurodegenerative Conditions and Acquired Spinal Disorders: Academic Advances and Clinical Prospects.}, journal = {Biology}, volume = {13}, number = {11}, pages = {}, pmid = {39596864}, issn = {2079-7737}, support = {2023//Spastic Paraplegia Foundation/ ; }, abstract = {Introduction: Quantitative spinal cord imaging has facilitated the objective appraisal of spinal cord pathology in a range of neurological conditions both in the academic and clinical setting. Diverse methodological approaches have been implemented, encompassing a range of morphometric, diffusivity, susceptibility, magnetization transfer, and spectroscopy techniques. Advances have been fueled both by new MRI platforms and acquisition protocols as well as novel analysis pipelines. The quantitative evaluation of specific spinal tracts and grey matter indices has the potential to be used in diagnostic and monitoring applications. The comprehensive characterization of spinal disease burden in pre-symptomatic cohorts, in carriers of specific genetic mutations, and in conditions primarily associated with cerebral disease, has contributed important academic insights. Methods: A narrative review was conducted to examine the clinical and academic role of quantitative spinal cord imaging in a range of neurodegenerative and acquired spinal cord disorders, including hereditary spastic paraparesis, hereditary ataxias, motor neuron diseases, Huntington's disease, and post-infectious or vascular disorders. Results: The clinical utility of specific methods, sample size considerations, academic role of spinal imaging, key radiological findings, and relevant clinical correlates are presented in each disease group. Conclusions: Quantitative spinal cord imaging studies have demonstrated the feasibility to reliably appraise structural, microstructural, diffusivity, and metabolic spinal cord alterations. Despite the notable academic advances, novel acquisition protocols and analysis pipelines are yet to be implemented in the clinical setting.}, } @article {pmid39596631, year = {2024}, author = {Sneha, NP and Dharshini, SAP and Taguchi, YH and Gromiha, MM}, title = {Tracing ALS Degeneration: Insights from Spinal Cord and Cortex Transcriptomes.}, journal = {Genes}, volume = {15}, number = {11}, pages = {}, pmid = {39596631}, issn = {2073-4425}, mesh = {*Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology ; Humans ; *Transcriptome ; *Spinal Cord/metabolism/pathology ; Frontal Lobe/metabolism/pathology ; Gene Regulatory Networks ; Motor Neurons/metabolism/pathology ; }, abstract = {BACKGROUND/OBJECTIVES: Amyotrophic Lateral Sclerosis is a progressive neurodegenerative disorder characterized by the loss of upper and lower motor neurons. Key factors contributing to neuronal death include mitochondrial energy damage, oxidative stress, and excitotoxicity. The frontal cortex is crucial for action initiation, planning, and voluntary movements whereas the spinal cord facilitates communication with the brain, walking, and reflexes. By investigating transcriptome data from the frontal cortex and spinal cord, we aim to elucidate common pathological mechanisms and pathways involved in ALS for understanding the disease progression and identifying potential therapeutic targets.

METHODS: In this study, we quantified gene and transcript expression patterns, predicted variants, and assessed their functional effects using computational tools. It also includes predicting variant-associated regulatory effects, constructing functional interaction networks, and performing a gene enrichment analysis.

RESULTS: We found novel genes for the upregulation of immune response, and the downregulation of metabolic-related and defective degradation processes in both the spinal cord and frontal cortex. Additionally, we observed the dysregulation of histone regulation and blood pressure-related genes specifically in the frontal cortex.

CONCLUSIONS: These results highlight the distinct and shared molecular disruptions in ALS, emphasizing the critical roles of immune response and metabolic dysfunction in neuronal degeneration. Targeting these pathways may provide new therapeutic avenues to combat neurodegeneration and preserve neuronal health.}, } @article {pmid39596615, year = {2024}, author = {Papapanagiotou, AP and Anthimidou, EA and Eleftherohorinos, IG and Giantsis, IA}, title = {Comparison of Molecularly Identified Resistant and Susceptible Johnsongrass (Sorghum halepense L.) Populations at ALS Gene, in the Absence and Presence of Field Crops.}, journal = {Genes}, volume = {15}, number = {11}, pages = {}, pmid = {39596615}, issn = {2073-4425}, mesh = {*Herbicide Resistance/genetics ; *Acetolactate Synthase/genetics ; *Sorghum/genetics/growth & development ; *Herbicides/pharmacology ; Plant Weeds/genetics/growth & development/drug effects ; Plant Proteins/genetics ; Zea mays/genetics/growth & development ; Crops, Agricultural/genetics/growth & development ; Genotype ; Biomass ; Helianthus/genetics/growth & development ; }, abstract = {BACKGROUND/OBJECTIVES: Johnsongrass (Sorghum halepense) is an erect tetraploid, perennial, C4 grass weed species categorized among the world's most noxious weeds due to its high competitive ability against crops and the increased number of field-evolved herbicide-resistant populations. The aim of the present study was to assess the growth rate and performance of resistant (R) johnsongrass genotypes hosting Trp574Leu target-site cross-resistance at ALS gene, inhibiting various herbicides, compared to susceptible (S) conspecific weeds, in the absence and presence of corn or sunflower antagonism.

METHODS: The aboveground biomass, tiller, and rhizome production ability of one S and one R johnsongrass population with a Trp574-Leu substitution conferring cross-resistance to ALS-inhibiting herbicides were compared under non-competitive conditions. Furthermore, the competitive ability of these two johnsongrass populations against corn or sunflower was determined in a target-neighborhood design.

RESULTS: The S and R johnsongrass populations displayed similar growth rates concerning aboveground biomass and tiller number, whereas the R population displayed a slightly greater growth rate for rhizome production compared to the S population. Both populations grown with corn produced more aboveground biomass than the ones grown with sunflowers. The aboveground biomass of corn was reduced to a greater extent than sunflower by the presence of both johnsongrass populations, while both crops were affected more by the S than by the R population.

CONCLUSIONS: Although the inheritance and the genetic background of plant materls were not addressed, the findings of this study indicate clearly that the growth rate and competitive ability of the ALS-resistant johnsongrass population are not associated with the resistance mechanism involved.}, } @article {pmid39596609, year = {2024}, author = {Luglio, A and Maggi, E and Riviello, FN and Conforti, A and Sorrentino, U and Zuccarello, D}, title = {Hereditary Neuromuscular Disorders in Reproductive Medicine.}, journal = {Genes}, volume = {15}, number = {11}, pages = {}, pmid = {39596609}, issn = {2073-4425}, support = {PNRR-MR1-2022-12376108//European Union/ ; }, mesh = {Humans ; *Neuromuscular Diseases/genetics/diagnosis ; Female ; Pregnancy ; Reproductive Medicine/methods ; Genetic Testing/methods ; Prenatal Diagnosis ; Preimplantation Diagnosis ; Muscular Atrophy, Spinal/genetics ; Charcot-Marie-Tooth Disease/genetics/diagnosis ; }, abstract = {Neuromuscular disorders (NMDs) encompass a broad range of hereditary and acquired conditions that affect motor units, significantly impacting patients' quality of life and reproductive health. This narrative review aims to explore in detail the reproductive challenges associated with major hereditary NMDs, including Charcot-Marie-Tooth disease (CMT), dystrophinopathies, Myotonic Dystrophy (DM), Facioscapulohumeral Muscular Dystrophy (FSHD), Spinal Muscular Atrophy (SMA), Limb-Girdle Muscular Dystrophy (LGMD), and Amyotrophic Lateral Sclerosis (ALS). Specifically, it discusses the stages of diagnosis and genetic testing, recurrence risk estimation, options for preimplantation genetic testing (PGT) and prenatal diagnosis (PND), the reciprocal influence between pregnancy and disease, potential obstetric complications, and risks to the newborn.}, } @article {pmid39596581, year = {2024}, author = {Paubel, A and Marouillat, S and Dangoumau, A and Maurel, C and Haouari, S and Blasco, H and Corcia, P and Laumonnier, F and Andres, CR and Vourc'h, P}, title = {Dynamic Expression of Genes Encoding Ubiquitin Conjugating Enzymes (E2s) During Neuronal Differentiation and Maturation: Implications for Neurodevelopmental Disorders and Neurodegenerative Diseases.}, journal = {Genes}, volume = {15}, number = {11}, pages = {}, pmid = {39596581}, issn = {2073-4425}, mesh = {Animals ; *Ubiquitin-Conjugating Enzymes/genetics/metabolism ; Mice ; *Neurons/metabolism ; *Neurodevelopmental Disorders/genetics/pathology ; *Neurodegenerative Diseases/genetics ; *Hippocampus/metabolism ; *Cell Differentiation/genetics ; Neurogenesis/genetics ; Cells, Cultured ; N-Methylaspartate/pharmacology/metabolism ; }, abstract = {Background: The ubiquitination process plays a crucial role in neuronal differentiation and function. Numerous studies have focused on the expression and functions of E3 ligases during these different stages, far fewer on E2 conjugating enzymes. In mice, as in humans, these E2s belong to 17 conjugating enzyme families. Objectives: We analyzed by real-time PCR the expression dynamics of all known E2 genes during an in vitro differentiation of mouse hippocampal neuronal cultures, and after, we analyzed their stimulation with N-methyl-D-aspartate (NMDA). Results: We found that 36 of the 38 E2 genes were expressed in hippocampal neurons. Many were up-regulated during neuritogenesis and/or synaptogenesis stages, such as Ube2h, Ube2b, and Aktip. Rapid and delayed responses to NMDA stimulation were associated with the increased expression of several E2 genes, such as Ube2i, the SUMO-conjugating E2 enzyme. We also observed similar expression profiles within the same E2 gene family, consistent with the presence of similar transcription factor binding sites in their respective promoter sequences. Conclusions: Our study indicates that specific expression profiles of E2 genes are correlated with changes in neuronal differentiation and activity. A better understanding of the regulation and function of E2s is needed to better understand the role played by the ubiquitination process in physiological mechanisms and pathophysiological alterations involved in neurodevelopmental or neurodegenerative diseases.}, } @article {pmid39596445, year = {2024}, author = {Jiang, LL and Zhang, XL and Hu, HY}, title = {Co-Aggregation of TDP-43 with Other Pathogenic Proteins and Their Co-Pathologies in Neurodegenerative Diseases.}, journal = {International journal of molecular sciences}, volume = {25}, number = {22}, pages = {}, pmid = {39596445}, issn = {1422-0067}, support = {31670782, 31700669//National Natural Science Foundation of China/ ; }, mesh = {Humans ; *Neurodegenerative Diseases/metabolism/pathology ; *DNA-Binding Proteins/metabolism ; *Protein Aggregation, Pathological/metabolism ; Animals ; Amyotrophic Lateral Sclerosis/metabolism/pathology ; Protein Aggregates ; }, abstract = {Pathological aggregation of a specific protein into insoluble aggregates is a common hallmark of various neurodegenerative diseases (NDDs). In the earlier literature, each NDD is characterized by the aggregation of one or two pathogenic proteins, which can serve as disease-specific biomarkers. The aggregation of these specific proteins is thought to be a major cause of or deleterious result in most NDDs. However, accumulating evidence shows that a pathogenic protein can interact and co-aggregate with other pathogenic proteins in different NDDs, thereby contributing to disease onset and progression synergistically. During the past years, more than one type of NDD has been found to co-exist in some individuals, which may increase the complexity and pathogenicity of these diseases. This article reviews and discusses the biochemical characteristics and molecular mechanisms underlying the co-aggregation and co-pathologies associated with TDP-43 pathology. The TDP-43 aggregates, as a hallmark of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD), can often be detected in other NDDs, such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD) and spinocerebellar ataxia type 2 (SCA2). In many cases, TDP-43 is shown to interact and co-aggregate with multiple pathogenic proteins in vitro and in vivo. Furthermore, the co-occurrence and co-aggregation of TDP-43 with other pathogenic proteins have important consequences that may aggravate the diseases. Thus, the current viewpoint that the co-aggregation of TDP-43 with other pathogenic proteins in NDDs and their relevance to disease progression may gain insights into the patho-mechanisms and therapeutic potential of various NDDs.}, } @article {pmid39595895, year = {2024}, author = {Pongrácová, E and Buratti, E and Romano, M}, title = {Prion-like Spreading of Disease in TDP-43 Proteinopathies.}, journal = {Brain sciences}, volume = {14}, number = {11}, pages = {}, pmid = {39595895}, issn = {2076-3425}, abstract = {TDP-43 is a ubiquitous nuclear protein that plays a central role in neurodegenerative disorders collectively known as TDP-43 proteinopathies. Under physiological conditions, TDP-43 is primarily localized to the nucleus, but in its pathological form it aggregates in the cytoplasm, contributing to neuronal death. Given its association with numerous diseases, particularly ALS and FTLD, the mechanisms underlying TDP-43 aggregation and its impact on neuronal function have been extensively investigated. However, little is still known about the spreading of this pathology from cell to cell. Recent research has unveiled the possibility that TDP-43 may possess prion-like properties. Specifically, misfolded TDP-43 aggregates can act as templates inducing conformational changes in native TDP-43 molecules and propagating the misfolded state across neural networks. This review summarizes the mounting and most recent evidence from in vitro and in vivo studies supporting the prion-like hypothesis and its underlying mechanisms. The prion-like behavior of TDP-43 has significant implications for diagnostics and therapeutics. Importantly, emerging strategies such as small molecule inhibitors, immunotherapies, and gene therapies targeting TDP-43 propagation offer promising avenues for developing effective treatments. By elucidating the mechanisms of TDP-43 spreading, we therefore aim to pave the way for novel therapies for TDP-43-related neurodegenerative diseases.}, } @article {pmid39595845, year = {2024}, author = {Rocha, PS and Bento, N and Svärd, H and Lopes, DM and Hespanhol, S and Folgado, D and Carreiro, AV and de Carvalho, M and Miranda, B}, title = {Voice Assessment in Patients with Amyotrophic Lateral Sclerosis: An Exploratory Study on Associations with Bulbar and Respiratory Function.}, journal = {Brain sciences}, volume = {14}, number = {11}, pages = {}, pmid = {39595845}, issn = {2076-3425}, support = {PTDC/MEC-NEU/6855/202//Fundação para a Ciência e Tecnologia/ ; }, abstract = {BACKGROUND: Speech production is a possible way to monitor bulbar and respiratory functions in patients with amyotrophic lateral sclerosis (ALS). Moreover, the emergence of smartphone-based data collection offers a promising approach to reduce frequent hospital visits and enhance patient outcomes. Here, we studied the relationship between bulbar and respiratory functions with voice characteristics of ALS patients, alongside a speech therapist's evaluation, at the convenience of using a simple smartphone.

METHODS: For voice assessment, we considered a speech therapist's standardized tool-consensus auditory-perceptual evaluation of voice (CAPE-V); and an acoustic analysis toolbox. The bulbar sub-score of the revised ALS functional rating scale (ALSFRS-R) was used, and pulmonary function measurements included forced vital capacity (FVC%), maximum expiratory pressure (MEP%), and maximum inspiratory pressure (MIP%). Correlation coefficients and both linear and logistic regression models were applied.

RESULTS: A total of 27 ALS patients (12 males; 61 years mean age; 28 months median disease duration) were included. Patients with significant bulbar dysfunction revealed greater CAPE-V scores in overall severity, roughness, strain, pitch, and loudness. They also presented slower speaking rates, longer pauses, and higher jitter values in acoustic analysis (all p < 0.05). The CAPE-V's overall severity and sub-scores for pitch and loudness demonstrated significant correlations with MIP% and MEP% (all p < 0.05). In contrast, acoustic metrics (speaking rate, absolute energy, shimmer, and harmonic-to-noise ratio) significantly correlated with FVC% (all p < 0.05).

CONCLUSIONS: The results provide supporting evidence for the use of smartphone-based recordings in ALS patients for CAPE-V and acoustic analysis as reliable correlates of bulbar and respiratory function.}, } @article {pmid39595818, year = {2024}, author = {Ferullo, L and Risi, B and Caria, F and Olivieri, E and Poli, L and Gazzina, S and Leggio, U and Bertella, E and Giovanelli, G and Labella, B and Padovani, A and Filosto, M}, title = {Gold Coast Criteria in ALS Diagnosis: A Real-World Experience.}, journal = {Brain sciences}, volume = {14}, number = {11}, pages = {}, pmid = {39595818}, issn = {2076-3425}, abstract = {Background: Revised El Escorial (rEEC) and Awaji criteria are currently used for diagnosing and categorizing amyotrophic lateral sclerosis (ALS). However, they are complex; their sensitivity is still not optimal for research purposes, and they present high inter-rater variability in clinical practice. To address these points, in 2019, a new set of diagnostic criteria was proposed, namely the Gold Coast criteria (GCC), characterized by a dichotomous diagnostic categorization, i.e., ALS or not ALS. Methods: In order to investigate the sensitivity, specificity, and clinical usefulness of GCC in a practical clinical setting, we retrospectively evaluated 131 patients diagnosed with ALS and 104 control subjects. ALSFRS-R score, electrophysiological tests, neuroradiological investigations, and CSF analysis were obtained. rEEC, Awaji, and GCC were applied at the first and last evaluations. Results: The sensitivity of GCC (93.1%; 96.1%) was greater than rEEC (71.8%; 87%) and Awaji criteria (77.8%; 89.3%) both at the first visit and last follow-up. The GCC's specificity (28.8%) is lower than that of the other two criteria (rEEC 45.2%; Awaji 43.3%). Conclusions: Our study suggests that in a real-world setting, the GCC are more sensitive and have substantially lower risk of false negative diagnoses than rEEC and Awaji criteria. Although rEEC had the highest specificity, they may delay the diagnosis. Systematically using the GCC could help to achieve an earlier diagnosis and quickly refer patients to the correct management. The low specificity of GCC is likely to not significantly impact patient recruitment in clinical trials; therefore, its use might allow a faster and earlier enrollment.}, } @article {pmid39595816, year = {2024}, author = {Shandiz, E and Fernandes, GL and Henkin, JS and McCombe, PA and Trajano, GS and Henderson, RD}, title = {Assessing the Effect of Riluzole on Motor Unit Discharge Properties.}, journal = {Brain sciences}, volume = {14}, number = {11}, pages = {}, pmid = {39595816}, issn = {2076-3425}, abstract = {Background. This study aims to determine if Riluzole usage can change the function and excitability of motor neurons. Methods. The clinical data and indices of motor neuron excitability were assessed using high-density surface EMG parameters from 80 ALS participants. The persistent inward current was assessed using the discharge rate from paired motor units obtained from the tibialis anterior muscle. This enabled the discharge rate at recruitment, peak discharge rates and the hysteresis of the recruitment-derecruitment frequencies (also known as delta F) to be calculated. Limbs were classified according to their strength. Results. No differences in these motor neuron discharge properties were found according to whether Riluzole was used. Conclusions. The possible interpretations of this finding are discussed.}, } @article {pmid39595812, year = {2024}, author = {Zhang, S and Yang, Y and Lv, X and Zhou, X and Zhao, W and Meng, L and Zhu, S and Zhang, Z and Wang, Y}, title = {Exosome Cargo in Neurodegenerative Diseases: Leveraging Their Intercellular Communication Capabilities for Biomarker Discovery and Therapeutic Delivery.}, journal = {Brain sciences}, volume = {14}, number = {11}, pages = {}, pmid = {39595812}, issn = {2076-3425}, support = {82171871//National Natural Science Foundation of China/ ; BK20230488//Youth Fund Project of the Jiangsu Province Basic Research Program (Natural Science Foundation)/ ; None//Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)/ ; }, abstract = {The inexorable progression of neurodegenerative diseases (NDs), including Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and multiple sclerosis, is closely related to irreversible brain decline. Accurately characterizing pathophysiological features and identifying reliable biomarkers for early diagnosis and optimized treatment are critical. Hindered by the blood-brain barrier (BBB), obtaining sensitive monitoring indicators for disease progression and achieving efficient drug delivery remain significant challenges. Exosomes, endogenous nanoscale vesicles that carry key bioactive substances, reflect the intracellular environment and play an important role in cell signaling. They have shown promise in traversing the BBB, serving dual roles as potential biomarkers for NDs and vehicles for targeted drug delivery. However, the specific mechanisms by which exosome influence NDs are not fully understood, necessitating further investigation into their attributes and functionalities in the context of NDs. This review explores how exosomes mediate multifaceted interactions, particularly in exacerbating pathogenic processes such as oxidative stress, neuronal dysfunction, and apoptosis integral to NDs. It provides a comprehensive analysis of the profound impact of exosomes under stress and disease states, assessing their prospective utility as biomarkers and drug delivery vectors, offering new perspectives for tackling these challenging diseases.}, } @article {pmid39595543, year = {2024}, author = {Stoccoro, A and Coppedè, F}, title = {Exposure to Metals, Pesticides, and Air Pollutants: Focus on Resulting DNA Methylation Changes in Neurodegenerative Diseases.}, journal = {Biomolecules}, volume = {14}, number = {11}, pages = {}, pmid = {39595543}, issn = {2218-273X}, mesh = {*DNA Methylation/drug effects ; Humans ; *Pesticides/toxicity/adverse effects ; *Neurodegenerative Diseases/genetics/metabolism/chemically induced ; *Epigenesis, Genetic/drug effects ; *Air Pollutants/toxicity/adverse effects ; Environmental Exposure/adverse effects ; Animals ; Metals, Heavy/toxicity/adverse effects ; Metals/toxicity/metabolism/adverse effects ; }, abstract = {Individuals affected by neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS), are dramatically increasing worldwide. Thus, several efforts are being made to develop strategies for stopping or slowing the spread of these illnesses. Although causative genetic variants linked to the onset of these diseases are known, they can explain only a small portion of cases. The etiopathology underlying the neurodegenerative process in most of the patients is likely due to the interplay between predisposing genetic variants and environmental factors. Epigenetic mechanisms, including DNA methylation, are central candidates in translating the effects of environmental factors in genome modulation, and they play a critical role in the etiology of AD, PD, and ALS. Among the main environmental exposures that have been linked to an increased risk for these diseases, accumulating evidence points to the role of heavy metals, pesticides, and air pollutants. These compounds could trigger neurodegeneration through different mechanisms, mainly neuroinflammation and the induction of oxidative stress. However, increasing evidence suggests that they are also capable of inducing epigenetic alterations in neurons. In this article, we review the available literature linking exposure to metals, pesticides, and air pollutants to DNA methylation changes relevant to neurodegeneration.}, } @article {pmid39595127, year = {2024}, author = {Cardona, F}, title = {Special Issue "Mechanisms and Novel Therapeutic Approaches for Neurodegenerative Diseases".}, journal = {Biomedicines}, volume = {12}, number = {11}, pages = {}, pmid = {39595127}, issn = {2227-9059}, abstract = {Neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS), are among the major health problems of the elderly, and represent a major global health challenge due to their increasing prevalence and complex pathophysiological mechanisms [...].}, } @article {pmid39594452, year = {2024}, author = {Dibwe, DF and Oba, S and Monde, S and Hui, SP}, title = {Inhibition of Accumulation of Neutral Lipids and Their Hydroperoxide Species in Hepatocytes by Bioactive Allium sativum Extract.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {13}, number = {11}, pages = {}, pmid = {39594452}, issn = {2076-3921}, abstract = {Our ongoing research suggests that extracts from plant-based foods inhibit the accumulation of lipid droplets (LDs) and oxidized lipid droplets (oxLDs) in liver cells. These findings suggest their potential use in the alleviation of metabolic dysfunction-associated fatty liver disease (MAFLD) and its most severe manifestation, metabolic dysfunction-associated steatohepatitis (MASH). Allium extracts (ALs: AL1-AL9) were used to assess their ability to reduce lipid droplet accumulation (LDA) and oxidized lipid droplet accumulation (oxLDA) by inhibiting neutral lipid accumulation and oxidation in LD. Among the tested Allium extracts, AL1, AL3, and AL6 demonstrated substantial inhibitory effects on the LDA. Furthermore, AL1 extract showed real-time inhibition of LDA in HepG2 cells in DMEM supplemented with oleic acid (OA) within 12 h of treatment. Our lipidomic approach was used to quantify the accumulation and inhibition of intracellular triacylglycerol (TAG) and oxidized TAG hydroperoxide [TG (OOH) n = 3] species in hepatocytes under OA and linoleic acid loading conditions. These results suggest that Allium-based foods inhibit LD accumulation by decreasing intracellular lipids and lipid hydroperoxides in the hepatocytes. The metabolomic analysis of AL1-the bioactive LDAI extract-using both LC-MS/MS and 1D-NMR [[1]H, [13]C, and Dept (135 and 90)] approaches revealed that AL1 contains mainly carbohydrates and glucoside metabolites, including iridoid glucosides, as well as minor amino acids, organosulfur compounds, and organic acids such as the antioxidant ascorbic acid (KA2 = S13), and their derivatives, suggesting that AL1 could be a potential resource for the development of functional foods and in drug discovery targeting MAFLD/MASH and other related diseases.}, } @article {pmid39593881, year = {2024}, author = {Favier, G and Rocha, DS}, title = {Overview of Tensor-Based Cooperative MIMO Communication Systems-Part 2: Semi-Blind Receivers.}, journal = {Entropy (Basel, Switzerland)}, volume = {26}, number = {11}, pages = {}, pmid = {39593881}, issn = {1099-4300}, abstract = {Cooperative MIMO communication systems play an important role in the development of future sixth-generation (6G) wireless systems incorporating new technologies such as massive MIMO relay systems, dual-polarized antenna arrays, millimeter-wave communications, and, more recently, communications assisted using intelligent reflecting surfaces (IRSs), and unmanned aerial vehicles (UAVs). In a companion paper, we provided an overview of cooperative communication systems from a tensor modeling perspective. The objective of the present paper is to provide a comprehensive tutorial on semi-blind receivers for MIMO one-way two-hop relay systems, allowing the joint estimation of transmitted symbols and individual communication channels with only a few pilot symbols. After a reminder of some tensor prerequisites, we present an overview of tensor models, with a detailed, unified, and original description of two classes of tensor decomposition frequently used in the design of relay systems, namely nested CPD/PARAFAC and nested Tucker decomposition (TD). Some new variants of nested models are introduced. Uniqueness and identifiability conditions, depending on the algorithm used to estimate the parameters of these models, are established. Two families of algorithms are presented: iterative algorithms based on alternating least squares (ALS) and closed-form solutions using Khatri-Rao and Kronecker factorization methods, which consist of SVD-based rank-one matrix or tensor approximations. In a second part of the paper, the overview of cooperative communication systems is completed before presenting several two-hop relay systems using different codings and configurations in terms of relaying protocol (AF/DF) and channel modeling. The aim of this presentation is firstly to show how these choices lead to different nested tensor models for the signals received at destination. Then, by capitalizing on these models and their correspondence with the generic models studied in the first part, we derive semi-blind receivers to jointly estimate the transmitted symbols and the individual communication channels for each relay system considered. In a third part, extensive Monte Carlo simulation results are presented to compare the performance of relay systems and associated semi-blind receivers in terms of the symbol error rate (SER) and channel estimate normalized mean-square error (NMSE). Their computation time is also compared. Finally, some perspectives are drawn for future research work.}, } @article {pmid39593143, year = {2024}, author = {Clarke, BE and Ziff, OJ and Tyzack, G and Petrić Howe, M and Wang, Y and Klein, P and Smith, CA and Hall, CA and Helmy, A and Howell, M and Kelly, G and Patani, R}, title = {Human VCP mutant ALS/FTD microglia display immune and lysosomal phenotypes independently of GPNMB.}, journal = {Molecular neurodegeneration}, volume = {19}, number = {1}, pages = {90}, pmid = {39593143}, issn = {1750-1326}, support = {/WT_/Wellcome Trust/United Kingdom ; }, mesh = {*Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology ; Humans ; *Microglia/metabolism ; *Membrane Glycoproteins/metabolism/genetics ; *Valosin Containing Protein/metabolism/genetics ; *Induced Pluripotent Stem Cells/metabolism ; *Frontotemporal Dementia/genetics/metabolism/pathology ; Animals ; *Lysosomes/metabolism ; Mice ; Mutation/genetics ; Phenotype ; Motor Neurons/metabolism/pathology ; Astrocytes/metabolism ; }, abstract = {BACKGROUND: Microglia play crucial roles in maintaining neuronal homeostasis but have been implicated in contributing to amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). However, the role of microglia in ALS/FTD remains incompletely understood.

METHODS: Here, we generated highly enriched cultures of VCP mutant microglia derived from human induced pluripotent stem cells (hiPSCs) to investigate their cell autonomous and non-cell autonomous roles in ALS pathogenesis. We used RNA-sequencing, proteomics and functional assays to study hiPSC derived VCP mutant microglia and their effects on hiPSC derived motor neurons and astrocytes.

RESULTS: Transcriptomic, proteomic and functional analyses revealed immune and lysosomal dysfunction in VCP mutant microglia. Stimulating healthy microglia with the inflammatory inducer lipopolysaccharide (LPS) showed partial overlap with VCP mutant microglia in their reactive transformation. LPS-stimulated VCP mutant microglia displayed differential activation of inflammatory pathways compared with LPS-stimulated healthy microglia. Conserved gene expression changes were identified between VCP mutant microglia, SOD1 mutant mice microglia, and postmortem ALS spinal cord microglial signatures, including increased expression of the transmembrane glycoprotein GPNMB. While knockdown of GPNMB affected inflammatory and phagocytosis processes in microglia, this was not sufficient to ameliorate cell autonomous phenotypes in VCP mutant microglia. Secreted factors from VCP mutant microglia were sufficient to activate the JAK-STAT pathway in hiPSC derived motor neurons and astrocytes.

CONCLUSIONS: VCP mutant microglia undergo cell autonomous reactive transformation involving immune and lysosomal dysfunction that partially recapitulate key phenotypes of microglia from other ALS models and post mortem tissue. These phenotypes occur independently of GPNMB. Additionally, VCP mutant microglia elicit non cell autonomous responses in motor neurons and astrocytes involving the JAK-STAT pathway.}, } @article {pmid39592088, year = {2025}, author = {Mahakalakar, N and Mohariya, G and Taksande, B and Kotagale, N and Umekar, M and Vinchurney, M}, title = {"Nattokinase as a potential therapeutic agent for preventing blood-brain barrier dysfunction in neurodegenerative disorders".}, journal = {Brain research}, volume = {1849}, number = {}, pages = {149352}, doi = {10.1016/j.brainres.2024.149352}, pmid = {39592088}, issn = {1872-6240}, mesh = {*Blood-Brain Barrier/drug effects/metabolism ; Humans ; Animals ; *Neurodegenerative Diseases/drug therapy/metabolism ; *Subtilisins/therapeutic use/pharmacology ; *Neuroprotective Agents/pharmacology/therapeutic use ; }, abstract = {Neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis are characterized by progressive destruction of neurons and cognitive impairment, and thorough studies have provided evidence that these pathologies have a close relationship to the failure of the blood-brain barrier (BBB). Nattokinase (NK), a protease found in fermented soybeans, has been extensively studied because it displays powerful neuroprotective abilities, which is why current research was reviewed in the present article. It was concluded that there is enough evidence in preclinical studies using experimental animals that NK supplementation can alleviate the condition related to BBB dysfunction, reduce brain inflammation, and improve cognitive ability. Furthermore, the study of NK on the cardiovascular system leads to certain assumptions, which include the impact on vasculature function and the ability to manage blood flow, which is the key feature of BBB integrity. Such assumed mechanisms are fibrinolytic action, anti-inflammatory and antioxidant action, and endothelium function modulation. There are many positive research findings, and it seems that NK may serve as an effective opponent for BBB breakdown; however, a new research level should be taken to disclose the application and therapeutic use of NK in brain neurodegenerative disease.}, } @article {pmid39592063, year = {2024}, author = {Lorenc, F and Dupuis, L and Cassel, R}, title = {Impairments of inhibitory neurons in amyotrophic lateral sclerosis and frontotemporal dementia.}, journal = {Neurobiology of disease}, volume = {203}, number = {}, pages = {106748}, doi = {10.1016/j.nbd.2024.106748}, pmid = {39592063}, issn = {1095-953X}, mesh = {*Amyotrophic Lateral Sclerosis/pathology/physiopathology ; *Frontotemporal Dementia/pathology/physiopathology ; Humans ; Animals ; *Neurons/pathology ; *Neural Inhibition/physiology ; }, abstract = {Amyotrophic lateral sclerosis and frontotemporal dementia are two fatal neurodegenerative disorders. They are part of a pathophysiological continuum, displaying clinical, neuropathological, and genetic overlaps. There is compelling evidence that neuronal circuit dysfunction is an early feature of both diseases. Impaired neuronal excitability, imbalanced excitatory and inhibitory influences, and altered functional connectivity have been reported. These phenomena are likely due to combined alterations in the various cellular components involved in the functioning of neuronal networks. This review focuses on one of these cellular components: inhibitory neurons. We assess the evidence for inhibitory neuron impairments in amyotrophic lateral sclerosis and frontotemporal dementia, as well as the mechanisms leading to the loss of inhibition. We also discuss the contributions of these alterations to symptoms, and the potential therapeutic strategies for targeting inhibitory neuron deficits.}, } @article {pmid39591907, year = {2024}, author = {Bajpai, A and Bharathi, V and Kumawat, R and Tomar, RS and Patel, BK}, title = {Activation of the yeast MAP kinase, Slt2, protects against TDP-43 and TDP-25 toxicity in the Saccharomyces cerevisiae proteinopathy model.}, journal = {Biochemical and biophysical research communications}, volume = {741}, number = {}, pages = {151062}, doi = {10.1016/j.bbrc.2024.151062}, pmid = {39591907}, issn = {1090-2104}, mesh = {*Saccharomyces cerevisiae/metabolism/genetics ; *Saccharomyces cerevisiae Proteins/metabolism/genetics ; *DNA-Binding Proteins/metabolism/genetics ; *Unfolded Protein Response/drug effects ; *Mitogen-Activated Protein Kinases/metabolism/genetics ; TDP-43 Proteinopathies/metabolism/genetics/pathology ; Humans ; Enzyme Activation ; Oxidative Stress/drug effects ; }, abstract = {TDP-43 proteinopathy is observed in human neurodegenerative diseases like ALS. Heterologous TDP-43 expression in the yeast model also mimics several proteinopathy features such as cytotoxicity, cytoplasmic mis-localization and oxidative stress. Among the pathways implicated in modulating the TDP-43 toxicity in yeast, the unfolded protein response (UPR) activation was also identified. Here, we examine the role of stress-regulated yeast MAP kinase, Slt2, which also links cellular stress with UPR activation, in modulating the toxicities of the full-length TDP-43 and its 25 kDa C-terminal fragment, TDP-25. We find enhancement in the cytotoxicity of TDP-43, as well as TDP-25, in the yeast cells deleted for the MAP kinase, Slt2, but not in those lacking other yeast MAP kinases, Kss1 and Fus3. Unlike in the wild-type yeast, upon treatment with an antioxidant N-acetyl cysteine, the TDP-43 toxicity could not be mitigated in the slt2Δ yeast but the TDP-25 toxicity was significantly rescued suggesting oxidative stress as an important contributor to the TDP-25 toxicity. Notably, TDP-43 as well as TDP-25 expressions could cause significant phosphorylation of Slt2 suggesting activation of this MAP Kinase due to their toxicities. Interestingly, in the slt2Δ cells, lacking the MAP Kinase activity, a treatment with low concentrations of an UPR activator molecule, DTT, caused significant reduction in the toxicities of both TDP-43 as well as TDP-25. Taken together, these findings suggest that TDP-43 and TDP-25 toxicity-induced stress-mediated activation of the MAP kinase Slt2 helps in mitigating their toxicities in the yeast model possibly through UPR activation.}, } @article {pmid39589985, year = {2024}, author = {Tkachenko, K and González-Saíz, JM and Calvo, AC and Lunetta, C and Osta, R and Pizarro, C}, title = {Comparative Blood Profiling Based on ATR-FTIR Spectroscopy and Chemometrics for Differential Diagnosis of Patients with Amyotrophic Lateral Sclerosis-Pilot Study.}, journal = {Biosensors}, volume = {14}, number = {11}, pages = {}, pmid = {39589985}, issn = {2079-6374}, support = {N· 801586//European Union's H2020/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/diagnosis/blood ; Humans ; Pilot Projects ; Diagnosis, Differential ; Spectroscopy, Fourier Transform Infrared ; Middle Aged ; Female ; Male ; Aged ; Adult ; Biomarkers/blood ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a motor neurodegenerative disease characterized by poor prognosis. Currently, screening and diagnostic methods for ALS remain challenging, often leading to diagnosis at an advanced stage of the disease. This delay hinders the timely initiation of therapy, negatively impacting patient well-being. Additionally, misdiagnosis with other neurodegenerative disorders that present similar profiles often occurs. Therefore, there is an urgent need for a cost-effective, rapid, and user-friendly tool capable of predicting ALS onset. In this pilot study, we demonstrate that infrared spectroscopy, coupled with chemometric analysis, can effectively identify and predict disease profiles from blood samples drawn from ALS patients. The selected predictive spectral markers, which are used in various discriminant models, achieved an AUROC sensitivity of almost 80% for distinguishing ALS patients from controls. Furthermore, the differentiation of ALS at both the initial and advanced stages from other neurodegenerative disorders showed even higher AUROC values, with sensitivities of 87% (AUROC: 0.70-0.97). These findings highlight the elevated potential of ATR-FTIR spectroscopy for routine clinical screening and early diagnosis of ALS.}, } @article {pmid39589981, year = {2024}, author = {Mohaček-Grošev, V and Škrabić, M and Gebavi, H and Blažek Bregović, V and Marić, I and Amendola, V and Grdadolnik, J}, title = {Binding of Glutamic Acid to Silver and Gold Nanoparticles Investigated by Surface-Enhanced Raman Spectroscopy.}, journal = {Biosensors}, volume = {14}, number = {11}, pages = {}, pmid = {39589981}, issn = {2079-6374}, support = {croatian-slovenian bilateral project//Ministry of Scirence and Education of the Republic of Croatia/ ; }, mesh = {*Spectrum Analysis, Raman ; *Glutamic Acid/chemistry ; *Silver/chemistry ; *Gold/chemistry ; *Metal Nanoparticles/chemistry ; Hydrogen-Ion Concentration ; }, abstract = {Glutamate is the most important excitatory neurotransmitter, which is relevant for the study of several diseases such as amyotrophic lateral sclerosis and Alzheimer. It is the form L-glutamic acid (Glu) takes at physiologically relevant pHs. The surface-enhanced Raman spectra of Glu obtained at pH values ranging from 3.3 to 12 are collected in the presence of silver and gold colloids and on solid substrates. The observed bands are compared with the positions of calculated normal modes for free neutral glutamic acid, glutamic acid monohydrate, glutamic acid bound to gold and silver atoms, and sodium glutamate. Although gold atoms prefer to bind to the NH2 group as compared to carbonyl groups, silver atoms prefer binding to hydroxyl groups more than binding to the amino group. SERS spectra of glutamic acid solutions with a pH value of 12, in which both carboxylic groups are deprotonated, indicate a complexation of the glutamic acid dianion with the sodium cation, which was introduced into the solution to adjust the pH value. Further research towards an optimal substrate is needed.}, } @article {pmid39589881, year = {2024}, author = {Jean Gregoire, M and Sirtori, R and Donatelli, L and Morgan Potts, E and Collins, A and Zamor, D and Katenka, N and Fallini, C}, title = {Early disruption of the CREB pathway drives dendritic morphological alterations in FTD/ALS cortical neurons.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {121}, number = {49}, pages = {e2406998121}, pmid = {39589881}, issn = {1091-6490}, support = {P20 GM103430/GM/NIGMS NIH HHS/United States ; Early Career Development Award//RI-INBRE/ ; R01NS116143//HHS | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; P20GM103430//HHS | NIH | National Institute of General Medical Sciences (NIGMS)/ ; R01 NS116143/NS/NINDS NIH HHS/United States ; }, mesh = {Humans ; *Dendrites/metabolism ; *Cyclic AMP Response Element-Binding Protein/metabolism ; *Frontotemporal Dementia/metabolism/genetics/pathology ; *Amyotrophic Lateral Sclerosis/metabolism/pathology/genetics ; Neurons/metabolism ; Cyclic AMP-Dependent Protein Kinases/metabolism/genetics ; Induced Pluripotent Stem Cells/metabolism ; Signal Transduction ; C9orf72 Protein/genetics/metabolism ; Phosphorylation ; Cerebral Cortex/metabolism/pathology ; }, abstract = {Synaptic loss and dendritic degeneration are common pathologies in several neurodegenerative diseases characterized by progressive cognitive and/or motor decline, such as Alzheimer's disease (AD) and frontotemporal dementia/amyotrophic lateral sclerosis (FTD/ALS). An essential regulator of neuronal health, the cAMP-dependent transcription factor CREB positively regulates synaptic growth, learning, and memory. Phosphorylation of CREB by protein kinase A (PKA) and other cellular kinases promotes neuronal survival and maturation via transcriptional activation of a wide range of downstream target genes. CREB pathway dysfunction has been strongly implicated in AD pathogenesis, and recent data suggest that impaired CREB activation may contribute to disease phenotypes in FTD/ALS as well. However, the mechanisms behind reduced CREB activity in FTD/ALS pathology are not clear. In this study, we found that cortical-like neurons derived from iPSC lines carrying the hexanucleotide repeat expansion in the C9ORF72 gene, a common genetic cause of FTD/ALS, displayed a diminished activation of CREB, resulting in decreased dendritic and synaptic health. Importantly, we determined such impairments to be mechanistically linked to an imbalance in the ratio of regulatory and catalytic subunits of the CREB activator PKA and to be conserved in C9-ALS patient's postmortem tissue. Modulation of cAMP upstream of this impairment allowed for a rescue of CREB activity and an amelioration of dendritic morphology and synaptic protein levels. Our data elucidate the mechanism behind early CREB pathway dysfunction and discern a feasible therapeutic target for the treatment of FTD/ALS and possibly other neurodegenerative diseases.}, } @article {pmid39589500, year = {2025}, author = {Apolloni, S and D'Ambrosi, N}, title = {Biochemical dissection of STAT3 signaling in amyotrophic lateral sclerosis.}, journal = {Neural regeneration research}, volume = {20}, number = {11}, pages = {3229-3230}, pmid = {39589500}, issn = {1673-5374}, } @article {pmid39589178, year = {2025}, author = {Peng, Y and Zhou, L and Jin, Y and Wu, D and Chen, N and Zhang, C and Liu, H and Li, C and Ning, R and Yang, X and Mao, Q and Liu, J and Zhang, P}, title = {Calcium bridges built by mitochondria-associated endoplasmic reticulum membranes: potential targets for neural repair in neurological diseases.}, journal = {Neural regeneration research}, volume = {20}, number = {12}, pages = {3349-3369}, pmid = {39589178}, issn = {1673-5374}, abstract = {The exchange of information and materials between organelles plays a crucial role in regulating cellular physiological functions and metabolic levels. Mitochondria-associated endoplasmic reticulum membranes serve as physical contact channels between the endoplasmic reticulum membrane and the mitochondrial outer membrane, formed by various proteins and protein complexes. This microstructural domain mediates several specialized functions, including calcium (Ca 2+) signaling, autophagy, mitochondrial morphology, oxidative stress response, and apoptosis. Notably, the dysregulation of Ca 2+ signaling mediated by mitochondria-associated endoplasmic reticulum membranes is a critical factor in the pathogenesis of neurological diseases. Certain proteins or protein complexes within these membranes directly or indirectly regulate the distance between the endoplasmic reticulum and mitochondria, as well as the transduction of Ca 2+ signaling. Conversely, Ca 2+ signaling mediated by mitochondria-associated endoplasmic reticulum membranes influences other mitochondria-associated endoplasmic reticulum membrane-associated functions. These functions can vary significantly across different neurological diseases-such as ischemic stroke, traumatic brain injury, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease-and their respective stages of progression. Targeted modulation of these disease-related pathways and functional proteins can enhance neurological function and promote the regeneration and repair of damaged neurons. Therefore, mitochondria-associated endoplasmic reticulum membranes-mediated Ca 2+ signaling plays a pivotal role in the pathological progression of neurological diseases and represents a significant potential therapeutic target. This review focuses on the effects of protein complexes in mitochondria-associated endoplasmic reticulum membranes and the distinct roles of mitochondria-associated endoplasmic reticulum membranes-mediated Ca 2+ signaling in neurological diseases, specifically highlighting the early protective effects and neuronal damage that can result from prolonged mitochondrial Ca 2+ overload or deficiency. This article provides a comprehensive analysis of the various mechanisms of Ca 2+ signaling mediated by mitochondria-associated endoplasmic reticulum membranes in neurological diseases, contributing to the exploration of potential therapeutic targets for promoting neuroprotection and nerve repair.}, } @article {pmid39588282, year = {2024}, author = {Dash, BP and Freischmidt, A and Helferich, AM and Ludolph, AC and Andersen, PM and Weishaupt, JH and Hermann, A}, title = {Upregulated miR-10b-5p as a potential miRNA signature in amyotrophic lateral sclerosis patients.}, journal = {Frontiers in cellular neuroscience}, volume = {18}, number = {}, pages = {1457704}, pmid = {39588282}, issn = {1662-5102}, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal, adult-onset disease marked by a progressive degeneration of motor neurons (MNs) present in the spinal cord, brain stem and motor cortex. Death in most patients usually occurs within 2-4 years after symptoms onset. Despite promising progress in delineating underlying mechanisms, such as disturbed proteostasis, DNA/RNA metabolism, splicing or proper nucleocytoplasmic shuttling, there are no effective therapies for the vast majority of cases. A reason for this might be the disease heterogeneity and lack of substantial clinical and molecular biomarkers. The identification and validation of such pathophysiology driven biomarkers could be useful for early diagnosis and treatment stratification. Recent advances in next generation RNA-sequencing approaches have provided important insights to identify key changes of non-coding RNAs (ncRNAs) implicated with ALS disease. Especially, microRNAs (miRNAs) have emerged as key post-transcriptional regulators of gene expression to target several genes/pathways by degrading messenger RNAs (mRNAs) or repressing levels of gene expression. In this study, we expand our previous work to identify top-regulated differentially expressed (DE)-miRNAs by combining different normalizations to search for important and generalisable pathomechanistic dysregulations in ALS as putative novel biomarkers of the disease. For this we performed a consensus pipeline of existing datasets to investigate the transcriptomic profile (mRNAs and miRNAs) of MN cell lines from iPSC-derived SOD1- and TARDBP (TDP-43 protein)-mutant-ALS patients and healthy controls to identify potential signatures and their related pathways associated with neurodegeneration. Transcriptional profiling of miRNA-mRNA interactions from MN cell lines in ALS patients revealed differential expression of genes showed greater vulnerability to KEAP1-NRF2 stress response pathway, sharing a common molecular denominator linked to both disease conditions. We also reported that mutations in above genes led to significant upregulation of the top candidate miR-10b-5p, which we could validate in immortalized lymphoblast cell lines (LCLs) derived from sporadic and familial ALS patients and postmortem tissues of familial ALS patients. Collectively, our findings suggest that miRNA analysis simultaneously performed in various human biological samples may reveal shared miRNA profiles potentially useful as a biomarker of the disease.}, } @article {pmid39587229, year = {2024}, author = {Wang, C and Wang, S and Xue, Y and Zhong, Y and Li, H and Hou, X and Kang, DD and Liu, Z and Tian, M and Wang, L and Cao, D and Yu, Y and Liu, J and Cheng, X and Markovic, T and Hashemi, A and Kopell, BH and Charney, AW and Nestler, EJ and Dong, Y}, title = {Intravenous administration of blood-brain barrier-crossing conjugates facilitate biomacromolecule transport into central nervous system.}, journal = {Nature biotechnology}, volume = {}, number = {}, pages = {}, pmid = {39587229}, issn = {1546-1696}, abstract = {Delivery of biomacromolecules to the central nervous system (CNS) remains challenging because of the restrictive nature of the blood-brain barrier (BBB). We developed a BBB-crossing conjugate (BCC) system that facilitates delivery into the CNS through γ-secretase-mediated transcytosis. Intravenous administration of a BCC10-oligonucleotide conjugate demonstrated effective transportation of the oligonucleotide across the BBB and gene silencing in wild-type mice, human brain tissues and an amyotrophic lateral sclerosis mouse model.}, } @article {pmid39585162, year = {2024}, author = {Savvidis, C and Kouroglou, E and Kallistrou, E and Ragia, D and Dionysopoulou, S and Gavriiloglou, G and Tsiama, V and Proikaki, S and Belis, K and Ilias, I}, title = {IGFBP-2 in Critical Illness: A Prognostic Marker in the Growth Hormone/Insulin-like Growth Factor Axis.}, journal = {Pathophysiology : the official journal of the International Society for Pathophysiology}, volume = {31}, number = {4}, pages = {621-630}, pmid = {39585162}, issn = {1873-149X}, abstract = {Critical illness (CI) triggers complex disruptions in the growth hormone (GH)/insulin-like growth factor (IGF) axis, significantly affecting the dynamics of insulin-like growth-factor-binding proteins (IGFBPs). Among these, IGFBP-2 shows a sustained elevation during CI, which inversely correlates with serum levels of IGF-1, IGFBP-3, and the acid-labile subunit (ALS). Although IGFBP-2 does not directly interact with ALS, it may influence the availability of IGFs by competing with other IGFBPs for binding to IGF-1 and IGF-2. Research suggests that this persistent elevation of IGFBP-2 is largely driven by cytokine activity during CI, reflecting an adaptive response rather than a direct result of GH/IGF axis dysregulation. The clinical importance of IGFBP-2 is emphasized by its correlation with disease severity in conditions like sepsis and coronavirus disease 2019 (COVID-19), where its levels are markedly elevated compared to healthy controls and are similar to those observed in sepsis from various causes. Beyond its role in endocrine regulation, IGFBP-2 appears to play a part in metabolic and inflammatory pathways. Elevated IGFBP-2 levels have been linked to increased mortality and longer hospital stays, indicating its potential utility as a prognostic marker. Furthermore, measuring plasma IGFBP-2 may have other diagnostic applications, aiding in the assessment of CI when traditional biomarkers are inconclusive.}, } @article {pmid39585060, year = {2024}, author = {Magni, E and Hochsprung, A and Cáceres-Matos, R and Pabón-Carrasco, M and Heredia-Camacho, B and Solís-Marcos, I and Luque-Moreno, C}, title = {Effects of Respiratory Training on Pulmonary Function, Cough, and Functional Independence in Patients with Amyotrophic Lateral Sclerosis.}, journal = {Neurology international}, volume = {16}, number = {6}, pages = {1332-1342}, pmid = {39585060}, issn = {2035-8385}, abstract = {BACKGROUND: Respiratory complications in patients with amyotrophic lateral sclerosis (ALS), due to the involvement of respiratory muscles, are the leading cause of death, and respiratory physiotherapy (RP) focuses on addressing these complications.

OBJECTIVES: The objective was to evaluate the effectiveness of an RP intervention that combines the four specific techniques (inspiratory muscle training, lung volume recruitment, manually assisted coughing, and diaphragmatic breathing training) in patients with ALS.

METHODS: A quasi-experimental study was carried out, and a specific RP programme was implemented in 15 patients with ALS (12 sessions, 30 min/session, one session/week, duration of three months), based on directed ventilation techniques, lung volume recruitment, manually assisted coughing, and the use of incentive spirometry and a cough assist device, along with a daily home exercise programme. Respiratory functions were assessed (pre- and post-intervention, with follow-up at three months) using Forced Vital Capacity (FVC) and Peak Expiratory Cough Flow (PECF); functionality was assessed using the Revised ALS Functional Rating Scale (ALSFRS-R) and the Modified Barthel Index by Granger.

RESULTS: FVC experienced an increase after three months of the intervention initiation (p = 0.30), which was not sustained at the three-month follow-up after the intervention ended. All other variables remained practically constant after treatment, with their values decreasing at follow-up.

CONCLUSION: A specific RP intervention could have beneficial effects on respiratory functions, potentially preventing pulmonary infections and hospitalisations in patients with ALS. It may improve FVC and help stabilize the patient's functional decline. Considering the progressive and degenerative nature of the disease, this finding could support the usefulness of these techniques in maintaining respiratory function.}, } @article {pmid39584466, year = {2025}, author = {Daneshpour, A and Rezvanimehr, A and Niktalab, P and Sharif, H and Yazdanpanah, N and Saleki, K and Rezaei, N}, title = {Exploring the role of vault complex in the nervous system: a literature review.}, journal = {Reviews in the neurosciences}, volume = {36}, number = {3}, pages = {327-338}, pmid = {39584466}, issn = {2191-0200}, mesh = {Humans ; Animals ; *Vault Ribonucleoprotein Particles/metabolism/genetics ; *Nervous System/metabolism ; }, abstract = {Vault RNAs (vtRNAs) are a novel group of non-coding RNAs that are involved in various signaling mechanisms. vtRNAs are joined by three proteins major vault protein (MVP), vault poly (ADP-ribose) polymerase (VPARP), and telomerase-associated protein 1 (TEP1) to form the vault complex. In humans, only four vtRNA including vtRNA 1-1, vtRNA 1-2, vtRNA 1-3, vtRNA 2-1) have been discovered. In nerve cells, vtRNA is involved in synapse formation through MAPK signaling. vtRNA travels to the distal area of neurites as a key unit in the vault complex. Moreover, tRNA is detached from the vault complex in the neurite via a mitotic kinase Aurora-A-reliant MVP phosphorylation. Several molecules contribute to the formation of vtRNAs. For instance, SRSF2 and NSUN2 and their attachment to vtRNA1-1 determines the production of small-vtRNAs. Through the same factors, vtRNAs could play a role in neurodevelopmental deficits. Addition the role of vtRNA expression and vault proteins has been recently studied in neurodegenerative disorders such as Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS) as well as brain cancers. While the mechanisms of vtRNA involvement in neurological disorders is not well-demonstrated, we believe this could be related to the impact of vtRNA regulation in autophagy, immunoregulation, RNA stability, cellular stress, apoptosis, and regulation of other epigenetic pathways. The present review captures the state-of-the-art regarding the role of vtRNAs in neurodevelopment, normal nervous system function, and neurological disorders.}, } @article {pmid39583905, year = {2024}, author = {Townley, MA}, title = {Spinneret spinning field ontogeny and life history observations in the spider Palpimanus uncatus (Araneae: Palpimanidae).}, journal = {The Journal of arachnology}, volume = {52}, number = {1}, pages = {41-70}, pmid = {39583905}, issn = {0161-8202}, support = {P20 GM113131/GM/NIGMS NIH HHS/United States ; }, abstract = {As in other Palpimanidae, two pairs of posterior spinnerets present in typical Araneomorphae are vestigial in Palpimanus uncatus Kulczyński, 1909, with only the anterior lateral spinneret (ALS) pair prominent. Nevertheless, in late juvenile and adult females, spigots appear in the ancestral posterior spinneret region (PS). Consistent with these spigots serving cylindrical silk glands, females construct substantial egg sacs. While juveniles and adults exhibit a compressed PS, in postembryos it is fully extended. Piriform silk gland (PI) spigots form a linear array on ALSs from the 1[st] stadium, increasing in number during ontogeny by addition of PIs of the tartipore-accommodated (T-A) subtype (i.e., functional during proecdyses). The number of T-A PIs added from one stadium to the next and locations occupied by their spigots often exhibit a stereotypic pattern, especially consistent in early instars. The number of non-T-A PIs remains constant through ontogeny from the 1[st] stadium: one per ALS rather than the two per ALS inferred in a few araneoids. The secondary major ampullate silk gland (2° MaA) spigot, primitively uni-shafted among araneomorphs, has become modified into a multi-shafted spigot with extended base, the number of shafts increasing during ontogeny. However, the multiple ducts that connect to the shafts continue to be accommodated during proecdysis by a single enormous tartipore. Sexual dimorphism is present, with late stadium females having greater numbers of T-A PI spigots and 2° MaA spigot shafts. Observations are presented pertaining to feeding behavior, sexual cannibalism (absent), habitat, winter diapause, numbers of molts, and longevity.}, } @article {pmid39582565, year = {2024}, author = {Byeon, H}, title = {Glymphatic system function in diverse glucose metabolism states.}, journal = {World journal of diabetes}, volume = {15}, number = {11}, pages = {2245-2250}, pmid = {39582565}, issn = {1948-9358}, abstract = {The rising prevalence of diabetes and prediabetes globally necessitates a deeper understanding of associated complications, including glymphatic system dysfunction. The glymphatic system, crucial for brain waste clearance, is implicated in cognitive decline and neurodegenerative diseases like Alzheimer's disease. This letter explores recent research on glymphatic function across different glucose metabolism states. Tian et al's study reveals significant glymphatic dysfunction in type 2 diabetes mellitus patients, evidenced by lower diffusion tensor imaging analysis along perivascular space indices compared to those with normal glucose metabolism and prediabetes. The research also reveals a link between glymphatic dysfunction and cognitive impairment. Additional research underscores the role of glymphatic impairment in neurodegenerative diseases. These findings highlight the importance of integrating glymphatic health into diabetes management and suggest potential biomarkers for early diagnosis and targeted therapeutic interventions.}, } @article {pmid39581840, year = {2025}, author = {Hannaford, A and Pavey, N and Menon, P and van den Bos, MAJ and Kiernan, MC and Simon, N and Vucic, S}, title = {Muscle ultrasound aids diagnosis in amyotrophic lateral sclerosis.}, journal = {Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology}, volume = {170}, number = {}, pages = {234-243}, doi = {10.1016/j.clinph.2024.11.008}, pmid = {39581840}, issn = {1872-8952}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnostic imaging/physiopathology ; Male ; Middle Aged ; Female ; Ultrasonography/methods ; Aged ; *Muscle, Skeletal/diagnostic imaging/physiopathology ; Cohort Studies ; Adult ; Prospective Studies ; }, abstract = {OBJECTIVE: There is a need for improved diagnostic tools in Amyotrophic Lateral Sclerosis (ALS). Our objective was to assess muscle ultrasound as a diagnostic tool in patients with ALS and determine a simplified screening protocol to aid implementation in clinical practice.

METHODS: Ultrasound of bulbar and limb muscles was prospectively performed on all patients referred to a single centre with suspected ALS. Clinical measures of disease severity and upper motor neuron impairment were also recorded. Receiver operating characteristic (ROC) curves were calculated to assess the diagnostic utility of muscle ultrasound.

RESULTS: 94 patients initially suspected of ALS were recruited to this observational cohort study. Forty-four were subsequently diagnosed as ALS and 50 as disease mimics. ALS patients demonstrated a higher frequency and more generalised distribution of fasciculations compared to mimics. A simplified 5 muscle screening protocol exhibited an AUC of 0.94 (95 %CI 0.89-0.99) in discriminating ALS from mimics. The presence of ≥ 3 fasciculating muscles detected using this screening protocol was 89 % sensitive and 88 % specific for the diagnosis of ALS.

CONCLUSIONS: Muscle ultrasound, screening as few as 5 muscles, has diagnostic utility in ALS.

SIGNIFICANCE: Muscle ultrasound enhances clinical diagnosis in ALS.}, } @article {pmid39581338, year = {2025}, author = {Kokona, B and Cunningham, NR and Quinn, JM and Jacobsen, DR and Garcia, FJ and Galindo, SM and Petrucelli, L and Stafford, WF and Laue, TM and Fairman, R}, title = {Studying C9orf72 dipeptide repeat polypeptide aggregation using an analytical ultracentrifuge equipped with fluorescence detection.}, journal = {Analytical biochemistry}, volume = {697}, number = {}, pages = {115720}, pmid = {39581338}, issn = {1096-0309}, support = {P40 OD018537/OD/NIH HHS/United States ; R15 NS081681/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; *C9orf72 Protein/genetics ; *Caenorhabditis elegans/genetics ; *Dipeptides/chemistry ; Ultracentrifugation ; Drosophila melanogaster/genetics ; Humans ; Protein Aggregates ; Amyotrophic Lateral Sclerosis/genetics ; Frontotemporal Dementia/genetics ; Peptides/chemistry/genetics/analysis ; Fluorescence ; }, abstract = {Sedimentation velocity, using an analytical ultracentrifuge equipped with fluorescence detection, and electrophoresis methods are used to study aggregation of proteins in transgenic animal model systems. Our previous work validated the power of this approach in an analysis of mutant huntingtin aggregation. We demonstrate that this method can be applied to another neurodegenerative disease studying the aggregation of three dipeptide repeats (DPRs) produced by aberrant translation of mutant c9orf72 containing large G4C2 hexanucleotide repeats. These repeat expansions are the most common cause of familial amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). We analyzed the aggregation patterns of (Gly-Pro)47, (Gly-Ala)50, and (Gly-Arg)50 fused to fluorescent proteins in samples prepared from D. melanogaster, and (Gly-Ala)50 in C. elegans, using AU-FDS and SDD-AGE. Results suggest that (GP)47 is largely monomeric. In contrast, (GA)50 forms both intermediate and large-scale aggregates. (GR)50 is partially monomeric with some aggregation noted in SDD-AGE analysis. The aggregation of this DPR is likely to represent co-aggregated states with DNA and/or RNA. The power of these methods is the ability to gather data on aggregation patterns and characteristics in animal model systems, which may then be used to interpret the mitigation of aggregation through genetic or molecular therapeutic interventions.}, } @article {pmid39580968, year = {2024}, author = {Lewandowski, SA and Kular, L and Jagodic, M}, title = {Epigenetic age acceleration as a biomarker of amyotrophic lateral sclerosis severity?.}, journal = {EBioMedicine}, volume = {110}, number = {}, pages = {105470}, pmid = {39580968}, issn = {2352-3964}, } @article {pmid39580792, year = {2025}, author = {Kaplan, E and Weissbach, A and Kadmon, G and Nahum, E and Stein, J}, title = {Plasma exchange using peripheral arterial and venous access in the pediatric intensive care unit.}, journal = {Transfusion}, volume = {65}, number = {1}, pages = {152-158}, pmid = {39580792}, issn = {1537-2995}, mesh = {Humans ; *Plasma Exchange/methods ; Retrospective Studies ; Child, Preschool ; Child ; *Intensive Care Units, Pediatric ; Female ; Male ; Infant ; *Catheterization, Peripheral/methods ; Adolescent ; Radial Artery ; }, abstract = {OBJECTIVE: Therapeutic plasma exchange (TPE) is a vital therapeutic modality in pediatric intensive care units (PICU) for various indications. Traditionally, pediatric TPE is performed via a large bore, double lumen catheter, whose insertion necessitates deep sedation, and poses risk of hemorrhagic and thrombotic complications. Building on our previous success utilizing percutaneous radial artery catheters (ALs) for apheresis procedures, we present our experience with ALs for TPE procedures in the PICU.

METHODS: A retrospective cohort study, conducted in the PICU of a tertiary, university affiliated pediatric hospital, including all children aged 19 years and younger, who underwent TPE using an AL for vascular access, between 2018 and 2023. TPE procedures were evaluated for utility (the procedure was performed as planned) and safety.

RESULTS: A total of 72 procedures were performed on 20 children, using ALs for inlet access and peripheral intra-venous catheters for blood return. Procedure success rate was 94%, with AL malfunction causing transient delays in 6%. All were successfully completed following AL replacement. ALs were mostly 20 and 22 gauge, predominantly located in the radial artery. AL gauge did not significantly affect flow rate or procedure duration.

CONCLUSIONS: Our findings support AL use for vascular access, as a viable alternative to the traditional large bore, double lumen catheters most often used for TPE in children. Benefits of AL use may include a decrease in sedation requirements and a lower risk of vascular complications. Further investigation is warranted, for consideration as routine practice in PICUs.}, } @article {pmid39579998, year = {2025}, author = {Baroukhian, J and Seiffert-Sinha, K and Sinha, AA}, title = {Response to Kasperkiewicz et al's "Pemphigus following herpes simplex infection: A global comprehensive cohort study".}, journal = {Journal of the American Academy of Dermatology}, volume = {92}, number = {4}, pages = {e99-e100}, doi = {10.1016/j.jaad.2024.07.1536}, pmid = {39579998}, issn = {1097-6787}, } @article {pmid39579996, year = {2025}, author = {Watanabe, Y and Yamaguchi, Y}, title = {Regarding response to Yamaguchi et al's "Anti-SS-A antibody is a potential predictor of severe Stevens-Johnson syndrome and toxic epidermal necrolysis: A retrospective cohort study".}, journal = {Journal of the American Academy of Dermatology}, volume = {92}, number = {3}, pages = {e73-e74}, doi = {10.1016/j.jaad.2024.11.030}, pmid = {39579996}, issn = {1097-6787}, } @article {pmid39579963, year = {2024}, author = {Carracedo, S and Launay, A and Dechelle-Marquet, PA and Faivre, E and Blum, D and Delarasse, C and Boué-Grabot, E}, title = {Purinergic-associated immune responses in neurodegenerative diseases.}, journal = {Progress in neurobiology}, volume = {243}, number = {}, pages = {102693}, doi = {10.1016/j.pneurobio.2024.102693}, pmid = {39579963}, issn = {1873-5118}, mesh = {Humans ; *Neurodegenerative Diseases/immunology/metabolism ; Animals ; *Receptors, Purinergic/metabolism ; }, abstract = {The chronic activation of immune cells can participate in the development of pathological conditions such as neurodegenerative diseases including Alzheimer's disease (AD), Multiple Sclerosis (MS), Parkinson's disease (PD), Huntington's disease (HD) and Amyotrophic Lateral Sclerosis (ALS). In recent years, compelling evidence indicates that purinergic signaling plays a key role in neuro-immune cell functions. The extracellular release of adenosine 5'-triphosphate (ATP), and its breakdown products (ADP and adenosine) provide the versatile basis for complex purinergic signaling through the activation of several families of receptors. G-protein coupled adenosine A2A receptors, ionotropic P2X and G-protein coupled P2Y receptors for ATP and other nucleotides are abundant and widely distributed in neurons, microglia, and astrocytes of the central nervous system as well as in peripheral immune cells. These receptors are strongly linked to inflammation, with a functional interplay that may influence the intricate purinergic signaling involved in inflammatory responses. In the present review, we examine the roles of the purinergic receptors in neuro-immune cell functions with particular emphasis on A2AR, P2X4 and P2X7 and their possible relevance to specific neurodegenerative disorders. Understanding the molecular mechanisms governing purinergic receptor interaction will be crucial for advancing the development of effective immunotherapies targeting neurodegenerative diseases.}, } @article {pmid39579350, year = {2024}, author = {Alfahel, L and Rajkovic, A and Israelson, A}, title = {Protocol for handling and using SOD1 mice for amyotrophic lateral sclerosis pre-clinical studies.}, journal = {STAR protocols}, volume = {5}, number = {4}, pages = {103459}, pmid = {39579350}, issn = {2666-1667}, mesh = {Animals ; *Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology ; Mice ; *Superoxide Dismutase-1/genetics/metabolism ; *Disease Models, Animal ; *Mice, Transgenic ; Female ; Male ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a devastating progressive neurodegenerative disease that has no proper cure. Pre-clinical studies on ALS mice are an essential milestone toward clinical trials. Here, we present a protocol for handling and using SOD1[G37R] mice for ALS pre-clinical studies. We describe steps for breeding, genotyping, monitoring, and behavioral testing of mice. We then detail procedures for perfusion, organ harvesting, and immunostaining for postmortem analysis. This protocol can be easily modified for other mouse lines. For complete details on the use and execution of this protocol, please refer to Alfahel et al.[1].}, } @article {pmid39578404, year = {2025}, author = {Phrathep, DD and Abdo, Z and Tadros, M and Lewandowski, E and Evans, J}, title = {The role of osteopathic manipulative treatment for dystonia: a literature review.}, journal = {Journal of osteopathic medicine}, volume = {125}, number = {4}, pages = {203-211}, pmid = {39578404}, issn = {2702-3648}, mesh = {Humans ; *Manipulation, Osteopathic/methods ; *Dystonia/therapy ; }, abstract = {CONTEXT: Dystonia is a movement disorder that causes involuntary muscle contractions leading to abnormal movements and postures, such as twisting. Dystonia is the third most common movement disorder in the United States, with as many as 250,000 people affected. Because of its complexity, dystonia presents a significant challenge in terms of management and treatment. Despite limited research, osteopathic manipulative treatment (OMT) has been considered as an adjunctive treatment due to its inexpensive and noninvasive nature, as opposed to other modalities such as botulinum toxin injections, deep brain stimulation (DBS), and transcranial magnetic stimulation, which are often expensive and inaccessible. OMT treatments performed in case studies and series such as balanced ligamentous tension/articular ligamentous strain (BLT/ALS), muscle energy (ME), high-velocity low-amplitude (HVLA), and myofascial release (MFR) have shown reduction of pain and muscle hypertonicity, including in patients with dystonia.

OBJECTIVES: The studies reviewed in this paper provide a snapshot of the literature regarding the current evidence of OMT's role for dystonia.

METHODS: A medical reference librarian conducted a thorough literature search across multiple databases including PubMed and Google Scholar to find articles relevant to the use of OMT for dystonia. The search employed a combination of Medical Subject Headings (MeSH) terms and keywords related to osteopathic medicine and dystonia to ensure precise retrieval of relevant articles within the last 20 years. Despite limited research on the topic, all four relevant reports found in the literature were selected for review.

RESULTS: Of the four relevant reports, case series and studies highlighted the potential benefits of OMT in managing dystonia, particularly cervical dystonia and foot dystonia. OMT has shown promising results addressing pain, stiffness, and impaired motor function. In cases of foot dystonia in Parkinson's disease, OMT has helped improve gait and reduce pain by targeting somatic dysfunctions (SDs) associated with dystonia, such as abnormalities in foot progression angle (FPA) and musculoskeletal imbalances. Also, OMT has been found to alleviate symptoms of cervical dystonia, including tremors, muscle spasms, and neck stiffness. These interventions performed in case studies and series led to improvements in gait biomechanics in foot dystonia and overall symptom severity in patients with cervical dystonia.

CONCLUSIONS: Currently, botulinum toxin, oral medications, physical therapy, and rehabilitation are commonly utilized in managing dystonia. The studies reviewed in this paper suggest that these treatments may lead to improvements in pain and muscle hypertonicity in patients with dystonia. It is important to investigate whether factors such as the type of dystonia (eg, focal vs. segmental) and its underlying cause (eg, idiopathic, trauma, infection, autoimmune, medication side effects) influence treatment outcomes. Further research is recommended to explore the role of OMT in managing dystonia.}, } @article {pmid39578133, year = {2025}, author = {Travaglia, A and Lal, S and Pullagura, SR}, title = {Advancing ALS research: public-private partnerships to accelerate drug and biomarker development.}, journal = {Trends in neurosciences}, volume = {48}, number = {1}, pages = {1-2}, doi = {10.1016/j.tins.2024.10.008}, pmid = {39578133}, issn = {1878-108X}, mesh = {*Amyotrophic Lateral Sclerosis/drug therapy ; Humans ; *Public-Private Sector Partnerships ; Biomarkers ; *Drug Development ; *Drug Discovery ; *Biomedical Research ; }, abstract = {Developing effective treatments for amyotrophic lateral sclerosis (ALS) has been hindered by both the complexity of the disease and decentralized research efforts. By fostering collaboration, standardization, and inclusivity, the Accelerating Medicines Partnership® (AMP®) ALS initiative aims to lay the foundation for future discoveries in ALS biomarkers and treatments.}, } @article {pmid39577830, year = {2025}, author = {Morikawa, K and Izumiya, Y and Takashio, S and Kawano, Y and Oguni, T and Kuyama, N and Oike, F and Yamamoto, M and Tabata, N and Ishii, M and Hanatani, S and Hoshiyama, T and Kanazawa, H and Matsuzawa, Y and Usuku, H and Yamamoto, E and Ueda, M and Tsujita, K}, title = {Early experience with daratumumab-containing regimens in patients with light-chain cardiac amyloidosis.}, journal = {Journal of cardiology}, volume = {85}, number = {6}, pages = {440-446}, doi = {10.1016/j.jjcc.2024.11.003}, pmid = {39577830}, issn = {1876-4738}, mesh = {Humans ; Male ; Aged ; Female ; *Immunoglobulin Light-chain Amyloidosis/drug therapy/mortality ; *Antibodies, Monoclonal/administration & dosage/therapeutic use ; Middle Aged ; Retrospective Studies ; Survival Rate ; Treatment Outcome ; *Heart Diseases/drug therapy/mortality ; }, abstract = {BACKGROUND: Immunoglobulin light-chain (AL) amyloidosis is a lethal condition resulting from misfolded immunoglobulin ALs produced by clonal CD38-positive plasma cells. Treatment with daratumumab, an anti-human CD38 monoclonal antibody, led to higher frequencies of complete hematologic response and better clinical outcomes compared with conventional treatment. This study sought to evaluate the survival benefit of daratumumab-containing regimens in patients with AL cardiac amyloidosis.

METHODS AND RESULTS: We examined 65 consecutive patients with AL cardiac amyloidosis (mean age: 67.2 ± 10.4 years, male: 69 %) who underwent chemotherapy. We divided patients into a daratumumab group, which used daratumumab-containing regimens before second-line treatment (n = 32), and a conventional treatment group (n = 33). Compared with the conventional treatment group, the daratumumab group tended to be older, but there were no significant differences between groups in biomarkers and echocardiographic parameters. A total of 26 patients (40 %) died (median follow-up duration: 395 days). Kaplan-Meier survival analysis showed that the daratumumab group had significantly lower mortality compared with the conventional treatment group (p = 0.04; log-rank test). Cox hazard analysis revealed that use of daratumumab-containing regimens was associated with lower mortality after adjustment for the revised Mayo staging of AL amyloidosis (hazard ratio: 0.32; 95 % confidence interval: 0.12 to 0.85; p = 0.02).

CONCLUSION: Daratumumab-containing regimens may be associated with improved survival in patients with AL cardiac amyloidosis.}, } @article {pmid39577774, year = {2025}, author = {Olesen, MA and Villavicencio-Tejo, F and Cuevas-Espinoza, V and Quintanilla, RA}, title = {Unknown roles of tau pathology in neurological disorders. Challenges and new perspectives.}, journal = {Ageing research reviews}, volume = {103}, number = {}, pages = {102594}, doi = {10.1016/j.arr.2024.102594}, pmid = {39577774}, issn = {1872-9649}, mesh = {Humans ; *tau Proteins/metabolism ; Animals ; *Nervous System Diseases/metabolism/pathology ; Tauopathies/metabolism/pathology ; Aging/metabolism/pathology ; }, abstract = {Aging presents progressive changes that increase the susceptibility of the central nervous system (CNS) to suffer neurological disorders (NDs). Several studies have reported that an aged brain suffering from NDs shows the presence of pathological forms of tau protein, a microtubule accessory protein (MAP) critical for neuronal function. In this context, accumulative evidence has shown a pivotal contribution of pathological forms of tau to Alzheimer's disease (AD) and tauopathies. However, current investigations have implicated tau toxicity in other NDs that affect the central nervous system (CNS), including Parkinson's disease (PD), Huntington's disease (HD), Traumatic brain injury (TBI), Multiple sclerosis (MS), and Amyotrophic lateral sclerosis (ALS). These diseases are long-term acquired, affecting essential functions such as motor movement, cognition, hearing, and vision. Previous evidence indicated that toxic forms of tau do not have a critical contribution to the genesis or progression of these diseases. However, recent studies have shown that these tau forms contribute to neuronal dysfunction, inflammation, oxidative damage, and mitochondrial impairment events that contribute to the pathogenesis of these NDs. Recent studies have suggested that these neuropathologies could be associated with a prion-like behavior of tau, which induces a pathological dissemination of these toxic protein forms to different brain areas. Moreover, it has been suggested that this toxic propagation of tau from neurons into neighboring cells impairs the function of glial cells, oligodendrocytes, and endothelial cells by affecting metabolic function and mitochondrial health and inducing oxidative damage by tau pathology. Therefore, in this review, we will discuss current evidence demonstrating the critical role of toxic tau forms on NDs not related to AD and how its propagation and induced-bioenergetics failure may contribute to the pathogenic mechanism present in these NDs.}, } @article {pmid39577687, year = {2025}, author = {Li, Z and Zhang, Y and Li, D and Du, X and Chen, L and Guo, Y}, title = {Microglial upregulation of CD109 expression in spinal cord of amyotrophic lateral sclerosis mouse model and its role in modulating inflammation and TGFβ/SMAD pathway.}, journal = {Neuroscience}, volume = {564}, number = {}, pages = {202-213}, doi = {10.1016/j.neuroscience.2024.11.053}, pmid = {39577687}, issn = {1873-7544}, mesh = {Animals ; *Amyotrophic Lateral Sclerosis/metabolism/pathology ; *Microglia/metabolism ; *Spinal Cord/metabolism/pathology ; *Up-Regulation ; Mice ; *Smad Proteins/metabolism ; *Signal Transduction/physiology ; *Disease Models, Animal ; *Antigens, CD/metabolism ; *Transforming Growth Factor beta/metabolism ; Mice, Transgenic ; Inflammation/metabolism ; Lipopolysaccharides/pharmacology ; Transforming Growth Factor beta1/metabolism ; }, abstract = {CD109 is a multifunctional coreceptor, whose function has been widely studied in tumor progression and metastasis. One of the reported primary roles of CD109 involves down-regulating TGFβ signaling. However, the role of CD109 in central nervous system, especially neurodegenerative disease, is barely known. Here, we examined the expression changes and cellular location of CD109 and TGFβ/SMAD pathway molecules in lumbar spinal cord of SOD1-G93A mice, and explored the role and mechanism of CD109 on LPS-treated BV2 microglia and primary microglia derived from SOD1-G93A mice. Our results showed an increased expression of CD109 and TGFβ/SMAD pathway molecules in lumbar spinal cord of SOD1-G93A mice. Further cellular localization analysis demonstrated that proliferating microglia contributed mainly to the upregulation of CD109 and TGFβ1. Moreover, CD109 intervention in vitro partially reduced inflammatory response and TGFβ/SMAD pathway activation in both LPS-treated BV2 microglia and primary SOD1-G93A microglia. Thus, CD109 was involved in pathogenesis of ALS mice, and interventions targeting on CD109 modulation could be a potential therapeutic strategy for ALS.}, } @article {pmid39577621, year = {2025}, author = {Reiche, L and Plaack, B and Lehmkuhl, M and Weyers, V and Gruchot, J and Picard, D and Perron, H and Remke, M and Knobbe-Thomsen, C and Reifenberger, G and Küry, P and Kremer, D}, title = {HERV-W envelope protein is present in microglial cells of the human glioma tumor microenvironment and differentially modulates neoplastic cell behavior.}, journal = {Microbes and infection}, volume = {27}, number = {5-6}, pages = {105460}, doi = {10.1016/j.micinf.2024.105460}, pmid = {39577621}, issn = {1769-714X}, mesh = {Humans ; *Microglia/virology/metabolism ; *Tumor Microenvironment ; *Endogenous Retroviruses ; Cell Line, Tumor ; *Glioma/virology/pathology ; Cell Movement ; Cell Proliferation ; *Gene Products, env/metabolism ; Cytokines/metabolism ; Coculture Techniques ; }, abstract = {Gliomas are the most common parenchymal tumors of the central nervous system (CNS). With regard to their still unclear etiology, several recent studies have provided evidence of a new category of pathogenic elements called human endogenous retroviruses (HERVs) which seem to contribute to the evolution and progression of many neurological diseases such as amyotrophic lateral sclerosis (ALS), schizophrenia, chronic inflammatory polyneuropathy (CIDP) and, particularly, multiple sclerosis (MS). In these diseases, HERVs exert effects on cellular processes such as inflammation, proliferation, and migration. In previous studies, we demonstrated that in MS, the human endogenous retrovirus type-W envelope protein (HERV-W ENV) interferes with lesion repair through the activation of microglia (MG), the innate myeloid immune cells of the CNS. Here, we now show that HERV-W ENV is also present in the microglial cells (MG) of the tumor microenvironment (TME) in gliomas. It modulates the behavior of glioblastoma (GBM) cell lines in GBM/MG cocultures by altering their gene expression, secreted cytokines, morphology, proliferation, and migration properties and could thereby contribute to key tumor properties.}, } @article {pmid39577228, year = {2025}, author = {Sojdeh, S and Safarkhani, M and Daneshgar, H and Aldhaher, A and Heidari, G and Nazarzadeh Zare, E and Iravani, S and Zarrabi, A and Rabiee, N}, title = {Promising breakthroughs in amyotrophic lateral sclerosis treatment through nanotechnology's unexplored frontier.}, journal = {European journal of medicinal chemistry}, volume = {282}, number = {}, pages = {117080}, doi = {10.1016/j.ejmech.2024.117080}, pmid = {39577228}, issn = {1768-3254}, mesh = {*Amyotrophic Lateral Sclerosis/drug therapy/therapy ; Humans ; *Nanotechnology ; Genetic Therapy ; Animals ; Drug Delivery Systems ; Neuroprotective Agents/chemistry/therapeutic use/pharmacology ; }, abstract = {This review explores the transformative potential of nanotechnology in the treatment and diagnosis of amyotrophic lateral sclerosis (ALS), a progressive neurodegenerative disorder characterized by motor neuron degeneration, muscle weakness, and eventual paralysis. Nanotechnology offers innovative solutions across various domains, including targeted drug delivery, neuroprotection, gene therapy and editing, biomarker detection, advanced imaging techniques, and tissue engineering. By enhancing the precision and efficacy of therapeutic interventions, nanotechnology facilitates key advancements such as crossing the blood-brain barrier, targeting specific cell types, achieving sustained therapeutic release, and enabling combination therapies tailored to the complex pathophysiology of ALS. Despite its immense promise, the clinical translation of these approaches faces challenges, including potential cytotoxicity, biocompatibility, and regulatory compliance, which must be addressed through rigorous research and testing. This review emphasizes the application of nanotechnology in targeted drug delivery and gene therapy/editing for ALS, drawing on the author's prior work with various nanotechnological platforms to illustrate strategies for overcoming similar obstacles in drug and gene delivery. By bridging the gap between cutting-edge technology and clinical application, this article aims to highlight the vital role of nanotechnology in shaping the future of ALS treatment.}, } @article {pmid39577115, year = {2024}, author = {Abdian, S and Fakhri, S and Moradi, SZ and Khirehgesh, MR and Echeverría, J}, title = {Saffron and its major constituents against neurodegenerative diseases: A mechanistic review.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {135}, number = {}, pages = {156097}, doi = {10.1016/j.phymed.2024.156097}, pmid = {39577115}, issn = {1618-095X}, mesh = {Animals ; Humans ; *Carotenoids/pharmacology/therapeutic use ; *Crocus/chemistry ; Cyclohexenes/pharmacology ; Glucosides/pharmacology ; *Neurodegenerative Diseases/drug therapy ; Neuroprotective Agents/chemistry/pharmacology ; Phytochemicals/pharmacology ; *Plant Extracts/chemistry/pharmacology/therapeutic use ; Signal Transduction/drug effects ; Terpenes/pharmacology ; Vitamin A/analogs & derivatives ; }, abstract = {BACKGROUND: Neurodegeneration has been recognized as the main pathophysiological alteration in the majority of brain-related diseases. Despite contemporary attempts to provide acceptable medicinal therapies, the conclusion has not been much beneficial. Besides, the complex pathophysiological mechanisms behind neurodegenerative diseases (NDDs) urge the needs for finding novel multi-target agents. Accordingly, saffron with major active constituents and as multi-targeting agents have shown beneficial effects in modulating NDDs with higher efficacy and lower side effects.

PURPOSE: The present study provides a systematic and comprehensive review of the existing in vitro, in vivo, and clinical data on the effectiveness, and signaling pathways of saffron and its key phytochemical components in the management of NDDs. The need to develop novel saffron delivery systems is also considered.

METHODS: Studies were identified through a systematic and comprehensive search in Science Direct, PubMed, and Scopus databases through April 30, 2024. The whole saffron major constituents (e.g., saffron, crocin, crocetin, picrocrocin, and safranal) and NDDs (e.g., neuro*, spinal cord injury, multiple sclerosis, amyotrophic lateral sclerosis, Huntington*, Parkinson*, Alzheimer*, and brain) were selected as keywords to find related studies. In the systematic analysis, 64 articles were directly included in the current study. Additional reports were added within the comprehensive studies in the review.

RESULTS: Saffron and its active metabolites crocin, crocetin, safranal, and picrocrocin have shown acceptable efficacy in managing NDDs like Alzheimer's disease, Parkinson's disease, Attention deficit hyperactivity disorder, depression, and other NDDs via modulating apoptotic (e.g., caspases, Bax/Bcl-2, cytochrome c, and death receptors), inflammatory (e.g., NF-κB, IL-1β, IL-6, TNF-α, and COX-2), and oxidative strass (e.g., Nrf2, GSH, GPx, CAT, SOD, MDA, ROS, and nitrite) signaling pathways. The presented in vitro, in vivo, and clinical evidences showed us a better future of controlling NDDs with higher efficacy, while decreasing associated side effects with no significant toxicity. Additionally, employing novel delivery systems could increase the efficacy of saffron phytoconstituents to resolve the issues pharmacokinetic limitations.

CONCLUSION: Saffron and its major constituents employ anti-inflammatory, anti-apoptotic and antioxidant mechanisms in modulating several dysregulated-signaling pathways in NDDs. However, further research is necessary to elucidate the precise underlying mechanisms in exploring the feasibility of using saffron active compounds against NDDs. More studies should focus on dose-response relationships, long-term effects, highlighting key mechanisms, and designing more well-controlled clinical trials. Additionally, developing stable and cost-benefit novel delivery systems in future works helps to remove the pharmacokinetic limitations of saffron major constituents.}, } @article {pmid39575748, year = {2024}, author = {Xu, Z and He, S and Begum, MM and Han, X}, title = {Myelin Lipid Alterations in Neurodegenerative Diseases: Landscape and Pathogenic Implications.}, journal = {Antioxidants & redox signaling}, volume = {41}, number = {16-18}, pages = {1073-1099}, pmid = {39575748}, issn = {1557-7716}, support = {P30 AG013319/AG/NIA NIH HHS/United States ; P30 AG044271/AG/NIA NIH HHS/United States ; R01 AG061729/AG/NIA NIH HHS/United States ; R01 AG085545/AG/NIA NIH HHS/United States ; }, mesh = {Humans ; *Neurodegenerative Diseases/metabolism ; *Myelin Sheath/metabolism ; *Lipid Metabolism ; Animals ; Lipids ; }, abstract = {Significance: Lipids, which constitute the highest portion (over 50%) of brain dry mass, are crucial for brain integrity, energy homeostasis, and signaling regulation. Emerging evidence revealed that lipid profile alterations and abnormal lipid metabolism occur during normal aging and in different forms of neurodegenerative diseases. Moreover, increasing genome-wide association studies have validated new targets on lipid-associated pathways involved in disease development. Myelin, the protective sheath surrounding axons, is crucial for efficient neural signaling transduction. As the primary site enriched with lipids, impairments of myelin are increasingly recognized as playing significant and complex roles in various neurodegenerative diseases, beyond simply being secondary effects of neuronal loss. Recent Advances: With advances in the lipidomics field, myelin lipid alterations and their roles in contributing to or reflecting the progression of diseases, including Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, multiple sclerosis, and others, have recently caught great attention. Critical Issues: This review summarizes recent findings of myelin lipid alterations in the five most common neurodegenerative diseases and discusses their implications in disease pathogenesis. Future Directions: By highlighting myelin lipid abnormalities in neurodegenerative diseases, this review aims to encourage further research focused on lipids and the development of new lipid-oriented therapeutic approaches in this area. Antioxid. Redox Signal. 00, 000-000.}, } @article {pmid39575564, year = {2025}, author = {Olofsson, J and Bergström, S and Mravinacová, S and Kläppe, U and Öijerstedt, L and Zetterberg, H and Blennow, K and Ingre, C and Nilsson, P and Månberg, A}, title = {Cerebrospinal fluid levels of NfM in relation to NfL and pNfH as prognostic markers in amyotrophic lateral sclerosis.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {26}, number = {1-2}, pages = {113-123}, doi = {10.1080/21678421.2024.2428930}, pmid = {39575564}, issn = {2167-9223}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/cerebrospinal fluid/diagnosis/mortality ; *Neurofilament Proteins/cerebrospinal fluid ; Male ; Female ; Middle Aged ; Prognosis ; Biomarkers/cerebrospinal fluid ; Aged ; Disease Progression ; Adult ; Cohort Studies ; Sweden ; }, abstract = {OBJECTIVE: To evaluate the prognostic potential of neurofilament medium chain (NfM) in CSF from patients with ALS and explore its relationship with the extensively studied neurofilament light chain (NfL) and phosphorylated heavy chain (pNfH).

METHOD: CSF levels of NfL, NfM, and pNfH were analyzed in 235 samples from patients with ALS, ALS mimics, and healthy controls in a well-characterized cohort from Karolinska ALS Clinical Research Center in Stockholm, Sweden. NfM levels were analyzed using an antibody-based suspension bead-array and NfL and pNfH levels were measured using ELISA. Clinical data, including ALS Revised Functional Rating Scale (ALSFRS-R), and survival outcomes were utilized for disease progression estimations.

RESULT: Increased NfM levels were observed in patients with ALS compared with mimics and healthy controls. Similarly, higher NfM levels were found in fast compared with slow progressing patients for baseline and longitudinal progression when evaluating both total and subscores of ALSFRS-R. These findings were consistent with the results observed for NfL and pNfH. All three proteins, used individually as well as in combination, showed comparable performance when classifying fast vs slow progressing patients (AUCs 0.78-0.85). For all neurofilaments, higher survival probability was observed for patients with low CSF levels.

CONCLUSION: Based on this cross-sectional study, the prognostic value provided by NfM aligns with the more established markers, NfL and pNfH. Additional investigations with independent cohorts and longitudinal studies are needed to further assess the potential added value of NfM.}, } @article {pmid39574866, year = {2024}, author = {Manohar, R and Yang, FX and Stephen, CD and Schmahmann, JD and Eklund, NM and Gupta, AS}, title = {At-home wearables and machine learning capture motor impairment and progression in adult ataxias.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, pmid = {39574866}, support = {R01 NS117826/NS/NINDS NIH HHS/United States ; R01 NS134597/NS/NINDS NIH HHS/United States ; }, abstract = {A significant barrier to developing disease-modifying therapies for spinocerebellar ataxias (SCAs) and multiple system atrophy of the cerebellar type (MSA-C) is the scarcity of tools to sensitively measure disease progression in clinical trials. Wearable sensors worn continuously during natural behavior at home have the potential to produce ecologically valid and precise measures of motor function by leveraging frequent and numerous high-resolution samples of behavior. Here we test whether movement-building block characteristics (i.e., submovements), obtained from the wrist and ankle during natural behavior at home, can sensitively capture disease progression in SCAs and MSA-C, as recently shown in amyotrophic lateral sclerosis (ALS) and ataxia telangiectasia (A-T). Remotely collected cross-sectional (n = 76) and longitudinal data (n = 27) were analyzed from individuals with ataxia (SCAs 1, 2, 3, and 6, MSA-C) and controls. Machine learning models were trained to produce composite outcome measures based on submovement properties. Two models were trained on data from individuals with ataxia to estimate ataxia rating scale scores. Two additional models, previously trained entirely on longitudinal ALS data to optimize sensitivity to change, were also evaluated. All composite outcomes from both wrist and ankle sensor data had moderate to strong correlations with ataxia rating scales and self-reported function, strongly separated ataxia and control populations, and had high within-week reliability. The composite outcomes trained on longitudinal ALS data most strongly captured disease progression over time. These data demonstrate that outcome measures based on accelerometers worn at home can accurately capture the ataxia phenotype and sensitively measure disease progression. This assessment approach is scalable and can be used in clinical or research settings with relatively low individual burden.}, } @article {pmid39574800, year = {2024}, author = {Bouajila, N and Domenighetti, C and Aubin, HJ and Naassila, M}, title = {Alcohol consumption and its association with cancer, cardiovascular, liver and brain diseases: a systematic review of Mendelian randomization studies.}, journal = {Frontiers in epidemiology}, volume = {4}, number = {}, pages = {1385064}, pmid = {39574800}, issn = {2674-1199}, abstract = {BACKGROUND: The health effects of alcohol consumption, particularly regarding potential protective benefits of light to moderate intake compared to abstinence, remain a subject of ongoing debate. However, epidemiological studies face limitations due to imprecise exposure measurements and the potential for bias through residual confounding and reverse causation. To address these limitations, we conducted a systematic review of Mendelian Randomization (MR) studies examining the causal relationship between alcohol consumption and cancers, cardiovascular, liver, and neurological diseases.

METHODOLOGY: We searched PubMed, ScienceDirect and Embase and Europe PMC up to 05/2024 for MR studies investigating the association of genetically predicted alcohol consumption with cancers, cardiovascular, liver and neurological diseases. We assessed methodological quality based on key elements of the MR design a genetic association studies tool.

RESULTS: We included 70 MR studies that matched our inclusion criteria. Our review showed a significant association of alcohol consumption with multiple cancers such as oral and oropharyngeal, esophageal, colorectal cancers, hepatocellular carcinoma and cutaneous melanoma. While the available studies did not consistently confirm the adverse or protective effects of alcohol on other cancers, such as lung cancer, as suggested by observational studies. Additionally, MR studies confirmed a likely causal effect of alcohol on the risk of hypertension, atrial fibrillation, myocardial infraction and vessels disease. However, there was no evidence to support the protective effects of light to moderate alcohol consumption on cognitive function, Alzheimer's disease, and amyotrophic lateral sclerosis, as reported in observational studies while our review revealed an increased risk of epilepsy and multiple sclerosis. The available studies provided limited results on the link between alcohol consumption and liver disease.

CONCLUSIONS: Despite the valuable insights into the causal relationship between alcohol consumption and various health outcomes that MR studies provided, it is worth noting that the inconsistent ability of genetic instrumental variables to distinguish between abstainers, light and moderate drinkers makes it difficult to differentiate between U or J-shaped vs. linear relationships between exposure and outcome. Additional research is necessary to establish formal quality assessment tools for MR studies and to conduct more studies in diverse populations, including non-European ancestries.

www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021246154, Identifier: PROSPERO (CRD42021246154).}, } @article {pmid39574607, year = {2024}, author = {Fürtjes, AE and Foote, IF and Xia, C and Davies, G and Moodie, J and Taylor, A and Liewald, DC and Redmond, P and Corley, J and McIntosh, AM and Whalley, HC and Maniega, SM and Hernández, MV and Backhouse, E and Ferguson, K and Bastin, ME and Wardlaw, J and de la Fuente, J and Grotzinger, AD and Luciano, M and Hill, WD and Deary, IJ and Tucker-Drob, EM and Cox, SR}, title = {Lifetime brain atrophy estimated from a single MRI: measurement characteristics and genome-wide correlates.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {39574607}, issn = {2692-8205}, support = {MR/M013111/1/MRC_/Medical Research Council/United Kingdom ; P2C HD042849/HD/NICHD NIH HHS/United States ; R01 AG073593/AG/NIA NIH HHS/United States ; /WT_/Wellcome Trust/United Kingdom ; R01 MH120219/MH/NIMH NIH HHS/United States ; P30 AG066614/AG/NIA NIH HHS/United States ; U54 MH091657/MH/NIMH NIH HHS/United States ; }, abstract = {A measure of lifetime brain atrophy (LBA) obtained from a single magnetic resonance imaging (MRI) scan could be an attractive candidate to boost statistical power in uncovering novel genetic signals and mechanisms of neurodegeneration. We analysed data from five young and old adult cohorts (MRi-Share, Human Connectome Project, UK Biobank, Generation Scotland Subsample, and Lothian Birth Cohort 1936 [LBC1936]) to test the validity and utility of LBA inferred from cross-sectional MRI data, i.e., a single MRI scan per participant. LBA was simply calculated based on the relationship between total brain volume (TBV) and intracranial volume (ICV), using three computationally distinct approaches: the difference (ICV-TBV), ratio (TBV/ICV), and regression-residual method (TBV~ICV). LBA derived with all three methods were substantially correlated with well-validated neuroradiological atrophy rating scales (r = 0.37-0.44). Compared with the difference or ratio method, LBA computed with the residual method most strongly captured phenotypic variance associated with cognitive decline (r = 0.36), frailty (r = 0.24), age-moderated brain shrinkage (r = 0.45), and longitudinally-measured atrophic changes (r = 0.36). LBA computed using a difference score was strongly correlated with baseline (i.e., ICV; r = 0.81) and yielded GWAS signal similar to ICV (rg = 0.75). We performed the largest genetic study of LBA to date (N = 43,110), which was highly heritable (h [2] SNP GCTA = 41% [95% CI = 38-43%]) and had strong polygenic signal (LDSC h [2] = 26%; mean χ2 = 1.23). The strongest association in our genome-wide association study (GWAS) implicated WNT16, a gene previously linked with neurodegenerative diseases such as Alzheimer, and Parkinson disease, and amyotrophic lateral sclerosis. This study is the first side-by-side evaluation of different computational approaches to estimate lifetime brain changes and their measurement characteristics. Careful assessment of methods for LBA computation had important implications for the interpretation of existing phenotypic and genetic results, and showed that relying on the residual method to estimate LBA from a single MRI scan captured brain shrinkage rather than current brain size. This makes this computationally-simple definition of LBA a strong candidate for more powerful analyses, promising accelerated genetic discoveries by maximising the use of available cross-sectional data.}, } @article {pmid39574440, year = {2024}, author = {Kaur, N and Verma, AK and Girdhar, M and Kumar, A and Siddiqui, MA and Al-Khedhairy, AA and Malik, T and Mohan, A}, title = {Genome-wide analysis of the Cannabis sativa cytochrome P450 monooxygenase superfamily and uncovering candidate genes for improved herbicide tolerance.}, journal = {Frontiers in plant science}, volume = {15}, number = {}, pages = {1490036}, pmid = {39574440}, issn = {1664-462X}, abstract = {Cannabis sativa is an economically important crop, yet weed management remains a significant challenge due to limited herbicide options. Cytochrome P450 enzymes play crucial roles in plant metabolism, including herbicide detoxification. This study aimed to identify and characterize the CYP gene family in Cannabis and investigate their potential role in herbicide metabolism. We identified 225 CYP proteins encoded by 221 genes in the Cannabis genome, classified into 9 clans and 47 families. The majority of CsCYPs were predicted to be located in endomembrane system and chromosomal mapping revealed that they were present in all the chromosomes. Motif and gene structure analysis supported the results from phylogenetic analysis. The gene duplication analysis results showed that tandem duplication plays a pivotal role in evolutionary expansion of CsCYP superfamily. Promoter analysis revealed various cis-acting elements involved in stress, light, hormone and development responses. Molecular docking simulations identified several CsCYPs with strong binding affinities to ALS-inhibiting herbicides, particularly bispyribac-sodium, propoxycarbazone-sodium, and pyriftalid. CsCYP_215, CsCYP_213, CsCYP_217 and CsCYP_14 emerged as promising candidates for herbicide metabolism. Analysis of binding site residues revealed the importance of hydrophobic and aromatic interactions in herbicide binding. This study provides the first comprehensive characterization of the CYP gene family in C. sativa and offers new insights into their potential roles in herbicide metabolism. The identification of promising herbicide-metabolizing CYP candidates opens new avenues for developing herbicide-tolerant Cannabis varieties, potentially addressing key challenges in weed management and crop productivity.}, } @article {pmid39572918, year = {2025}, author = {Changkakoti, L and Rajabalaya, R and David, SR and Balaraman, AK and Sivasubramanian, H and Mukherjee, AK and Bala, A}, title = {Exploration of the Role of Vitamins in Preventing Neurodegenerative Diseases: Comprehensive Review on Preclinical and Clinical Findings.}, journal = {Current neuropharmacology}, volume = {23}, number = {5}, pages = {547-563}, pmid = {39572918}, issn = {1875-6190}, mesh = {Humans ; *Neurodegenerative Diseases/prevention & control ; Animals ; *Vitamins/therapeutic use ; }, abstract = {Neurodegenerative diseases (NDDs) are a multifaceted and heterogeneous group of complex diseases. Unfortunately, a cure for these conditions has yet to be found, but there are ways to reduce the risk of developing them. Studies have shown that specific vitamins regulate the brain molecules and signaling pathways, which may help prevent degeneration. This review focuses on examining the role of vitamins in preventing five significant types of neurodegenerative diseases, including Parkinson's disease (PD), Alzheimer's disease (AD), Huntington's disease (HD), Multiple Sclerosis (MS), and Amyotrophic Lateral Sclerosis (ALS). This review also highlights promising and controversial findings about the potential impact of vitamins on this group of diseases. Several developed countries standardize daily dietary vitamin intake to meet nutrient requirements, improve health, and prevent chronic diseases like NDDs. However, more research is necessary to gain a more comprehensive understanding of their therapeutic benefits, including studies exploring different drug-dose paradigms, diverse humanized animal models, and clinical trials conducted in various locations.}, } @article {pmid39572390, year = {2025}, author = {Morales, JMN and Alcaraz, MR and Loto, A and Parellada, EA and Tulli, F and Morán Vieyra, FE and Borsarelli, CD}, title = {Chemometric modeling of spectroscopic data for characterizing the visible-light-driven photocatalytic N-dealkylation of rhodamine B on a TiO2 film.}, journal = {Photochemistry and photobiology}, volume = {101}, number = {4}, pages = {1000-1012}, doi = {10.1111/php.14043}, pmid = {39572390}, issn = {1751-1097}, support = {PIP-2020-101043CO//Consejo Nacional de Investigaciones Científicas y Técnicas/ ; PUE-2018-035//Consejo Nacional de Investigaciones Científicas y Técnicas/ ; PICT-2019-02052//Fondo para la Investigación Científica y Tecnológica/ ; 23A/254//Universidad Nacional de Santiago del Estero/ ; }, abstract = {The green-light driven photocatalytic N-deethylation reaction of Rhodamine B (RhB) on a TiO2 film was investigated by UV-vis absorption and fluorescence emission spectroscopies, in addition to HPLC and HR-MS, to ascertain the nature of the reaction products. The evolution of the photocatalytic reaction was chemometrically analyzed using Multivariate Curve Resolution-Alternating Least Squares (MCR-ALS) of the spectroscopic data to obtain the kinetic and spectral decomposition of the RhB derivatives involved in the reaction. This was then compared with the results obtained by standard HPLC analysis. The MCR-ALS analysis yielded satisfactory spectral and kinetic profiles for RhB and the fully deethylated product, Rhodamine 110. However, the spectral profiles for the N-triethyl (3EtRh) and the mixture of the two isomeric N-diethyl (2EtRh) derivatives exhibited some spectral distortions due to significant spectral overlap between these compounds. In contrast to the HPLC analysis, the MCR-ALS could not resolve the N-ethylrhodamine (EtRh) derivative. The deethylation reactions occurred via independent zero-order steps at the surface of TiO2, indicating that the RhB degradation reaction is governed by the adsorption-desorption equilibrium of the dye and derivatives on the photocatalyst surface, thereby enhancing the diffusion of compounds on the surface.}, } @article {pmid39572211, year = {2025}, author = {Benatar, M and Heiman-Patterson, TD and Cooper-Knock, J and Brickman, D and Casaletto, KB and Goutman, SA and Vinceti, M and Dratch, L and Arias, JJ and Swidler, J and Turner, MR and Shefner, J and Westeneng, HJ and van den Berg, LH and Al-Chalabi, A and , }, title = {Guidance for clinical management of pathogenic variant carriers at elevated genetic risk for ALS/FTD.}, journal = {Journal of neurology, neurosurgery, and psychiatry}, volume = {96}, number = {3}, pages = {}, pmid = {39572211}, issn = {1468-330X}, support = {/WT_/Wellcome Trust/United Kingdom ; R01 NS105479/NS/NINDS NIH HHS/United States ; U01 NS107027/NS/NINDS NIH HHS/United States ; U54 NS092091/NS/NINDS NIH HHS/United States ; }, abstract = {There is a growing understanding of the presymptomatic stages of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) and nascent efforts aiming to prevent these devastating neurodegenerative diseases have emerged. This progress is attributable, in no small part, to the altruism of people living with pathogenic variants at elevated genetic risk for ALS/FTD via their willingness to participate in natural history studies and disease prevention trials. Increasingly, this community has also highlighted the urgent need to develop paradigms for providing appropriate clinical care for those at elevated risk for ALS and FTD. This manuscript summarises recommendations emanating from a multi-stakeholder Workshop (Malvern, Pennsylvania, 2023) that aimed to develop guidance for at-risk carriers and their treating physicians. Clinical care recommendations span genetic testing (including counselling and sociolegal implications); monitoring for the emergence of early motor, cognitive and behavioural signs of disease; and the use of Food and Drug Administration-approved small molecule drugs and gene-targeting therapies. Lifestyle recommendations focus on exercise, smoking, statin use, supplement use, caffeine intake and head trauma, as well as occupational and environmental exposures. While the evidence base to inform clinical and lifestyle recommendations is limited, this guidance document aims to appraise carriers and clinicians of the issues and best available evidence, and also to define the research agenda that could yield more evidence-informed guidelines.}, } @article {pmid39572209, year = {2024}, author = {Grassano, M}, title = {Navigating the presymptomatic frontier in genetic ALS and FTD.}, journal = {Journal of neurology, neurosurgery, and psychiatry}, volume = {}, number = {}, pages = {}, doi = {10.1136/jnnp-2024-334924}, pmid = {39572209}, issn = {1468-330X}, } @article {pmid39571437, year = {2025}, author = {Parastar, H and Yazdanpanah, H and Weller, P}, title = {Non-targeted volatilomics for the authentication of saffron by gas chromatography-ion mobility spectrometry and multivariate curve resolution.}, journal = {Food chemistry}, volume = {465}, number = {Pt 2}, pages = {142074}, doi = {10.1016/j.foodchem.2024.142074}, pmid = {39571437}, issn = {1873-7072}, mesh = {*Crocus/chemistry ; *Ion Mobility Spectrometry/methods ; Food Contamination/analysis ; Gas Chromatography-Mass Spectrometry ; Volatile Organic Compounds/chemistry/analysis ; Discriminant Analysis ; Multivariate Analysis ; Principal Component Analysis ; Least-Squares Analysis ; Iran ; }, abstract = {In the present contribution, a novel non-targeted volatilomic study based on headspace GC-IMS (HS-GC-IMS) was developed for the authentication and geographical origin discrimination of saffron. In this regard, multivariate curve resolution-alternating least squares (MCR-ALS) was employed to recover the pure GC elution and IMS profiles of saffron metabolites. Iranian saffron samples from seven important areas were analyzed by HS-GC-IMS. The resulting second-order GC-IMS datasets were organized in a augmented matrix and processed using MCR-ALS with various constraints. The MCR-ALS resolved GC profiles were analyzed by different pattern recognition techniques; principal component analysis (PCA), partial least squares-discriminant analysis (PLS-DA) and data driven-soft independent modeling of class analogy (DD-SIMCA). The saffron samples were assigned to their seven geographical origins with an accuracy of 89.0 %. Additionally, four adulterants (style, safflower, madder and calendula) were reliably detected with over 94.0 % accuracy. In this context, GC-IMS substantially outperformed the commonly used FT-NIR spectroscopy approach.}, } @article {pmid39571211, year = {2025}, author = {Wang, Z and Wu, P and Zhao, Y and Li, X and Kong, D}, title = {Application of excitation-emission matrix fluorescence spectroscopy and chemometrics for quantitative analysis of emulsified oil concentration.}, journal = {Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy}, volume = {328}, number = {}, pages = {125423}, doi = {10.1016/j.saa.2024.125423}, pmid = {39571211}, issn = {1873-3557}, abstract = {Emulsified oil concentration is an important index for quantitative analysis of sea surface oil spill pollution, and the development of a fast and effective quantitative analysis method for emulsified oil concentration plays a crucial role in the estimation of oil spill volume and post-spill assessment. A quantitative analysis method for emulsified oil concentration based on excitation-emission matrix (EEM) fluorescence spectroscopy and chemometrics was proposed. Firstly, the EEM fluorescence spectra of two emulsified oils were measured using a FLS1000 fluorescence spectrometer. Then, the measured EEM fluorescence spectra were decomposed by parallel factor analysis (PARAFAC), and several key excitation wavelengths were filtered from the loading matrix obtained from the decomposition. Subsequently, the three-band fluorescence index (TBFI) at these excitation wavelengths was calculated and combined with the optimal band selection algorithm, from which the optimal emission band combinations were selected. Finally, the selected optimal emission bands were combined with partial least squares regression (PLSR) to establish a prediction model for emulsified oil concentration. By comparing the prediction results with those based on PARAFAC-PLSR and multivariate curve resolved-alternating least squares (MCR-ALS)-PLSR models, the TBFI-PLSR model showed the best results in the quantitative analysis of emulsified oil concentration. The coefficient of determination, mean square relative error, and ratio of performance to interquartile distance for the gasoline and diesel fuel emulsion validation sets were 0.93, 3.67%, 4.72, and 0.93, 3.72%, 4.60, respectively.}, } @article {pmid39570667, year = {2025}, author = {Burks, CA and Brenner, MJ}, title = {Commentary on Von Sneidern et al's "Evaluation and Treatment of Acute Facial Palsy: Opportunities for Optimization at a Single Institution."-Bridging the Gap Between Guidelines and Practice.}, journal = {Facial plastic surgery & aesthetic medicine}, volume = {27}, number = {4}, pages = {319-320}, doi = {10.1089/fpsam.2024.0263}, pmid = {39570667}, issn = {2689-3622}, } @article {pmid39570437, year = {2025}, author = {Maity, D and Kaundal, RK}, title = {Exploring dysregulated miRNAs in ALS: implications for disease pathogenesis and early diagnosis.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {46}, number = {4}, pages = {1661-1686}, pmid = {39570437}, issn = {1590-3478}, mesh = {*Amyotrophic Lateral Sclerosis/diagnosis/genetics/metabolism ; Humans ; *MicroRNAs/metabolism/genetics ; Early Diagnosis ; Biomarkers/metabolism ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease marked by motor neuron degeneration, leading to muscle weakness and paralysis, with no effective treatments available. Early diagnosis could slow disease progression and optimize treatment. MicroRNAs (miRNAs) are being investigated as potential biomarkers due to their regulatory roles in cellular processes and stability in biofluids. However, variability across studies complicates their diagnostic utility in ALS. This study aims to identify significantly dysregulated miRNAs in ALS through meta-analysis to elucidate disease mechanisms and improve diagnostic strategies.

METHODS: We systematically searched PubMed, Google Scholar, and the Cochrane Library, following predefined inclusion and exclusion criteria. The primary effect measure was the standardized mean difference (SMD) with a 95% confidence interval, analyzed using a random-effects model. Additionally, we used network pharmacology to examine the targets of dysregulated miRNAs and their roles in ALS pathology.

RESULTS: Analysing 34 studies, we found significant upregulation of hsa-miR-206, hsa-miR-133b, hsa-miR-23a, and hsa-miR-338-3p, and significant downregulation of hsa-miR-218, hsa-miR-21-5p, and hsa-let-7b-5p in ALS patients. These miRNAs are involved in ALS pathophysiology, including stress granule formation, nuclear pore complex, SMCR8 and Sig1R dysfunction, histone methyltransferase complex alterations, and MAPK signaling perturbation, highlighting their critical role in ALS progression.

CONCLUSION: This study identifies several dysregulated miRNAs in ALS patients, offering insights into their role in the disease and potential as diagnostic biomarkers. These findings enhance our understanding of ALS mechanisms and may inform future diagnostic strategies. Validating these results and exploring miRNA-based interventions are crucial for improving ALS diagnosis and treatment outcomes.}, } @article {pmid39569894, year = {2024}, author = {Brannigan, JFM and Liyanage, K and Horsfall, HL and Bashford, L and Muirhead, W and Fry, A}, title = {Brain-computer interfaces patient preferences: a systematic review.}, journal = {Journal of neural engineering}, volume = {21}, number = {6}, pages = {}, doi = {10.1088/1741-2552/ad94a6}, pmid = {39569894}, issn = {1741-2552}, mesh = {*Brain-Computer Interfaces ; Humans ; *Patient Preference ; Adult ; Middle Aged ; Spinal Cord Injuries/rehabilitation/psychology/physiopathology ; Amyotrophic Lateral Sclerosis/psychology/rehabilitation/physiopathology ; }, abstract = {Objective. Brain-computer interfaces (BCIs) have the potential to restore motor capabilities and functional independence in individuals with motor impairments. Despite accelerating advances in the performance of implanted devices, few studies have identified patient preferences underlying device design, and each study typically captures a single aetiology of motor impairment. We aimed to characterise BCI patient preferences in a large cohort across multiple aetiologies.Approach. We performed a systematic review of all published studies reporting patient preferences for BCI devices, including both qualitative and quantitative data. We searched MEDLINE, Embase, and CINAHL from inception to 18 April 2023. Two reviewers independently screened articles and extracted data on demographic information, device use, invasiveness preference, device design, and functional preferences.Main results. From 1316 articles identified, 28 studies met inclusion criteria, capturing preferences from 1701 patients (mean age 42.1-64.3 years). The most represented conditions were amyotrophic lateral sclerosis (n= 15 studies, 53.6%) and spinal cord injury (n= 13 studies 46.4%). Individuals with motor impairments prioritised device accuracy over other design characteristics. In four studies where patients ranked performance characteristics, accuracy was ranked first each time. We found that the speed and accuracy of BCI systems in recent publications exceeds reported patient preferences, however this performance has been achieved with a level of training and setup burden that would not be tolerated by most patients. Preferences varied by disease aetiology and severity; amyotrophic lateral sclerosis patients typically prioritised communication functions, whereas spinal cord injury patients emphasised limb control and sphincteric functions.Significance.Our findings highlight that despite advances in BCI performance exceeding patient expectations, there remains a need to reduce training and setup burdens to enhance usability. Moreover, patient preferences differ across conditions and impairment severities, underscoring the importance of personalised BCI configurations and tailored training regimens to meet individual needs.}, } @article {pmid39569650, year = {2025}, author = {Luo, S and Wang, X and Ma, B and Liu, D and Li, L and Wang, L and Ding, N and Zou, L and Wang, J and Pan, J and Sang, D and Zhou, H and Qu, H and Lu, Y and Yang, L}, title = {Therapeutic potential of simvastatin in ALS: Enhanced axonal integrity and motor neuron survival through Apoa4 and Alb modulation.}, journal = {Biomolecules & biomedicine}, volume = {25}, number = {3}, pages = {632-647}, pmid = {39569650}, issn = {2831-090X}, mesh = {*Simvastatin/pharmacology/therapeutic use ; *Amyotrophic Lateral Sclerosis/drug therapy/genetics/pathology ; Motor Neurons/drug effects/pathology ; Cell Survival/drug effects/genetics ; Mice, Inbred C57BL ; Animals ; Mice ; Mice, Transgenic ; Disease Models, Animal ; Superoxide Dismutase-1/genetics ; *Apolipoproteins A/genetics/metabolism ; Gene Expression Regulation/drug effects ; *Albumins/genetics/metabolism ; Axons/drug effects/metabolism/pathology ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the selective death of motor neurons in the spinal cord, brainstem, and motor cortex. This study investigates the effects of simvastatin on the G93A-copper/zinc superoxide dismutase (G93ASOD1) transgenic mouse model of ALS. The experiment included three groups: C57BL/6 wild-type mice, C57BL/6J SOD1G93A mice treated with PBS (SOD1G93A + PBS), and C57BL/6J SOD1G93A mice treated with simvastatin (SOD1G93A + simvastatin). The primary endpoints were survival rates, body weight changes, performance in pole climbing and suspension tests, and neurological deficit scores. Pathological changes were assessed using hematoxylin and eosin staining, transmission electron microscopy, Nissl staining, and Masson staining. Proteomic and metabolomic analyses were performed to identify differentially expressed proteins (DEPs) and metabolites. Quantitative real-time polymerase chain reaction and western blotting were used to measure gene expression. Although there were no significant differences in survival rates, body weight, pole climbing, and suspension test performance, or neurological deficit scores between the SOD1G93A + simvastatin and SOD1G93A + PBS groups, simvastatin treatment improved axonal organization within the spinal cord, increased the number of neurons, and reduced cytoplasmic swelling and gastrocnemius fibrosis. A total of 47 DEPs and 13 differential metabolites were identified between the SOD1G93A + PBS and SOD1G93A + simvastatin groups. Notably, the expression levels of Apoa4 and Alb were elevated in the SOD1G93A + simvastatin group compared to the SOD1G93A + PBS group. Our results suggest that simvastatin may have potential therapeutic effects in ALS, likely involving the modulation of Apoa4 and Alb expression.}, } @article {pmid39569145, year = {2024}, author = {Mirceta, M and Schmidt, MHM and Shum, N and Prasolava, TK and Meikle, B and Lanni, S and Mohiuddin, M and Mckeever, PM and Zhang, M and Liang, M and van der Werf, I and Scheers, S and Dion, PA and Wang, P and Wilson, MD and Abell, T and Philips, EA and Sznajder, ŁJ and Swanson, MS and Mehkary, M and Khan, M and Yokoi, K and Jung, C and de Jong, PJ and Freudenreich, CH and McGoldrick, P and Yuen, RKC and Abrahão, A and Keith, J and Zinman, L and Robertson, J and Rogaeva, E and Rouleau, GA and Kooy, RF and Pearson, CE}, title = {C9orf72 expansion creates the unstable folate-sensitive fragile site FRA9A.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2024.10.26.620312}, pmid = {39569145}, issn = {2692-8205}, abstract = {The hyper-unstable Chr9p21 locus, harbouring the interferon gene cluster, oncogenes and C9orf72, is linked to multiple diseases. C9orf72 (GGGGCC)n expansions (C9orf72 Exp) are associated with incompletely penetrant amyotrophic lateral sclerosis, frontotemporal dementia and autoimmune disorders. C9orf72 Exp patients display hyperactive cGAS-STING-linked interferon immune and DNA damage responses, but the source of immuno-stimulatory or damaged DNA is unknown. Here, we show C9orf72 Exp in pre-symptomatic and ALS-FTD patient cells and brains cause the folate-sensitive chromosomal fragile site, FRA9A. FRA9A centers on >33kb of C9orf72 as highly-compacted chromatin embedded in an 8.2Mb fragility zone spanning 9p21, encompassing 46 genes, making FRA9A one of the largest fragile sites. C9orf72 Exp cells show chromosomal instability, heightened global- and Chr9p-enriched sister-chromatid exchanges, truncated-Chr9s, acentric-Chr9s and Chr9-containing micronuclei, providing endogenous sources of damaged and immunostimulatory DNA. Cells from one C9orf72 Exp patient contained highly-rearranged FRA9A-expressing Chr9 with Chr9-wide dysregulated gene expression. Somatic C9orf72 Exp repeat instability and chromosomal fragility are sensitive to folate-deficiency. Age-dependent repeat instability, chromosomal fragility, and chromosomal instability can be transferred to CNS and peripheral tissues of transgenic C9orf72 Exp mice, implicating C9orf72 Exp as the source. Our results highlight unappreciated effects of C9orf72 expansions that trigger vitamin-sensitive chromosome fragility, adding structural variations to the disease-enriched 9p21 locus, and likely elsewhere.}, } @article {pmid39568840, year = {2024}, author = {Souayah, N and Chong, ZZ and Patel, T and Nasar, A and Pahwa, A and W Sander, H}, title = {Regression equation analysis enhances detection of conduction slowing beyond axonal loss in diabetic neuropathy.}, journal = {Heliyon}, volume = {10}, number = {21}, pages = {e39712}, pmid = {39568840}, issn = {2405-8440}, abstract = {OBJECTIVES: To evaluate the utility of regression analysis in the assessment of conduction slowing in diabetic distal symmetrical polyneuropathy (DSP) and in identifying superimposed demyelination beyond fiber loss.

BACKGROUND: Causes of conduction slowing beyond pure axonal loss has been attributed to an additional demyelinating component. We therefore evaluated the utility of regression analysis in the assessment of conduction slowing in diabetic DSP and in identifying superimposed demyelination beyond fiber loss.

METHODS: We previously established regression analysis to develop confidence intervals that assess the range of conduction slowing from primary demyelination in patients with chronic inflammatory demyelinating polyneuropathy (CIDP). In this study, by using the regression equations, we analyzed conduction slowing in patients with diabetic DSP.

RESULTS: Mean conduction velocity (CV) was significantly slower in diabetic DSP than in the non-diabetic DSP for all tested nerves. More patients were found to fulfill the regression equation criteria in the diabetic group compared to the non-diabetic group (47.0 % vs. 23.3 %). The estimated likelihood of having more than two motor nerves with CV slowing in the demyelination range by American Academy of Neurology or regression equations criteria was significantly higher in the diabetic DSP (0.73) compared to non-diabetic DSP (0.52).

CONCLUSIONS: Conduction slowing in diabetic DSP beyond what is expected exclusively from axonal loss could be identified by regression analysis.}, } @article {pmid39568376, year = {2025}, author = {Held-Bradford, EC and Sells, M and Longhurst, JK and Doherty, M}, title = {Variation in amyotrophic lateral sclerosis presentation and outcomes based on phenotype and physical therapy movement system diagnosis: a case series.}, journal = {Physiotherapy theory and practice}, volume = {41}, number = {7}, pages = {1519-1528}, doi = {10.1080/09593985.2024.2430745}, pmid = {39568376}, issn = {1532-5040}, mesh = {Aged ; Female ; Humans ; Middle Aged ; *Amyotrophic Lateral Sclerosis/physiopathology/diagnosis/therapy/rehabilitation ; Disability Evaluation ; Disease Progression ; Phenotype ; *Physical Therapy Modalities ; Treatment Outcome ; }, abstract = {BACKGROUND: Amyotrophic Lateral Sclerosis (ALS) is a progressive motor neuron disease and presentation varies. There is limited description of this variability and how physical therapy (PT) specific movement system diagnoses (MSD) may impact care.

PURPOSE: The purpose of this case series is to describe the variability of ALS presentation longitudinally across early, middle, and late stages of ALS based on phenotype and MSD.

METHODS: Four individuals were selected from an ALS clinic chart review representing a unique combination of phenotypes and MSDs (Case 1: bulbar onset force production deficit (FPD), Case 2: bulbar onset fractionated movement deficit (FMD), Case 3: limb onset FPD, Case 4: limb onset FMD). Descriptions of care over 9 years included outcomes of disability (ALS Functional Rating scale-revised), activity (10 Meter Walk Test, Five Times Sit to Stand Test, Trunk Impairment Scale-version 2), and impairment (strength and spasticity).

RESULTS: Persons with ALS were seen every 3 to 6 months (10 to 19 visits total). Determination of MSD was hardest to complete in early stage bulbar onset ALS. Patterns of decline through stages varied by MSD and phenotype, most notably in length of time in middle stage. Limb onset FMD had the slowest progression. Falls and fall related injuries were most frequent in limb onset ALS but falls occurred in all cases.

CONCLUSION: The combination of MSD and phenotype enhanced variability description offers new insights into clinical decision-making in ALS care.}, } @article {pmid39568060, year = {2024}, author = {Abbas, AEF and Abdelshafi, NA and Gamal, M and Halim, MK and Said, BAM and Naguib, IA and Mansour, MMA and Morshedy, S and Salem, YA}, title = {Simultaneously quantifying a novel five-component anti- migraine formulation containing ergotamine, propyphenazone, caffeine, camylofin, and mecloxamine using UV spectrophotometry and chemometric models.}, journal = {BMC chemistry}, volume = {18}, number = {1}, pages = {233}, pmid = {39568060}, issn = {2661-801X}, support = {TU-DSPP-2024-49//Taif University/ ; }, abstract = {This study presents a new method for simultaneously quantifying a complex anti-migraine formulation containing five components (ergotamine, propyphenazone, caffeine, camylofin, and mecloxamine) using UV spectrophotometry and chemometric models. The formulation presents analytical challenges due to the wide variation in component concentrations (ERG: PRO: CAF: CAM: MEC ratio of 0.075:20:8:5:4) and highly overlapping UV spectra. To create a comprehensive validation dataset, the Kennard-Stone Clustering Algorithm was used to address the limitations of arbitrary data partitioning in chemometric methods. Three different chemometric models were evaluated: Classical Least Squares (CLS), Partial Least Squares (PLS), and Multivariate Curve Resolution-Alternating Least Squares (MCR-ALS). Among these, MCR-ALS demonstrated excellent performance, achieving recovery values of 98-102% for all components, accompanied by minimal root mean square errors of calibration (0.072-0.378) and prediction (0.077-0.404). Moreover, the model exhibited high accuracy, with relative errors ranging from 1.936 to 3.121%, bias-corrected mean square errors between 0.074 and 0.389, and a good sensitivity (0.2097-1.2898 μg mL[-1]) for all components. The Elliptical Joint Confidence Region analysis further confirmed the predictive performance of the models, with MCR-ALS consistently showing the smallest ellipses closest to the ideal point (slope = 1, intercept = 0) for most analytes, indicating superior accuracy and precision. The approach's sustainability was rigorously assessed using six advanced metrics, validating its environmental friendliness, economic viability, and practical application. This approach effectively resolves complex pharmaceutical formulations, contributing to sustainable development objectives in quality control processes.}, } @article {pmid39567497, year = {2024}, author = {Zhu, Z and Song, M and Ren, J and Liang, L and Mao, G and Chen, M}, title = {Copper homeostasis and cuproptosis in central nervous system diseases.}, journal = {Cell death & disease}, volume = {15}, number = {11}, pages = {850}, pmid = {39567497}, issn = {2041-4889}, mesh = {Humans ; *Copper/metabolism ; *Homeostasis ; *Central Nervous System Diseases/metabolism/pathology ; Animals ; }, abstract = {Copper (Cu), an indispensable micronutrient for the sustenance of living organisms, contributes significantly to a vast array of fundamental metabolic processes. The human body maintains a relatively low concentration of copper, which is mostly found in the bones, liver, and brain. Despite its low concentration, Cu plays a crucial role as an indispensable element in the progression and pathogenesis of central nervous system (CNS) diseases. Extensive studies have been conducted in recent years on copper homeostasis and copper-induced cell death in CNS disorders, including glioma, Alzheimer's disease, Amyotrophic lateral sclerosis, Huntington's disease, and stroke. Cuproptosis, a novel copper-induced cell death pathway distinct from apoptosis, necrosis, pyroptosis, and ferroptosis, has been identified as potentially intricately linked to the pathogenic mechanisms underlying various CNS diseases. Therefore, a systematic review of copper homeostasis and cuproptosis and their relationship with CNS disorders could deepen our understanding of the pathogenesis of these diseases. In addition, it may provide new insights and strategies for the treatment of CNS disorders.}, } @article {pmid39567371, year = {2024}, author = {Nuzum, ND and Deady, C and Kittel-Schneider, S and Cryan, JF and O'Mahony, SM and Clarke, G}, title = {More than just a number: the gut microbiota and brain function across the extremes of life.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2418988}, pmid = {39567371}, issn = {1949-0984}, mesh = {*Gastrointestinal Microbiome/physiology ; Humans ; *Brain/microbiology ; Animals ; Brain-Gut Axis/physiology ; Alzheimer Disease/microbiology/physiopathology ; Neurodegenerative Diseases/microbiology ; }, abstract = {Understanding the interrelationship between the gut microbiota and host physiology, although still in its relative infancy, has taken important steps forward over the past decade. In the context of brain disorders including those characterized by neurodevelopmental and neurodegenerative changes there have been important advances. However, initially research involved correlational analyses, had limited translational scope, and lacked functional assessments. Thus, largescale longitudinal clinical investigations that assess causation and underlying mechanisms via in depth analysis methods are needed. In neurodegeneration research, strong causal evidence now links the gut microbiome to Alzheimer's (AD), and Parkinson's Disease (PD), as supported by human-to-animal transplantation studies. Longitudinal interventions are being conducted in AD, PD, amyotrophic lateral sclerosis, Huntington's disease, and multiple sclerosis. Neurodevelopmental research has also seen a boon in microbiome-related clinical research including in autism, Attention-deficit/hyperactivity disorder, and schizophrenia, which is confirming prior animal model work regarding the key time-windows in the gut microbiome important for infant cognition. While recent research advances represent important progress, fundamental knowledge gaps and obstacles remain. Knowing how and why the gut microbiome changes at the extremes of life will develop our mechanistic understanding and help build the evidence base as we strive toward counteracting microbial missteps with precision therapeutic interventions.}, } @article {pmid39565466, year = {2025}, author = {Crowley, PD and Mira, P and Saleh, OMA}, title = {Minocycline susceptibility in Stenotrophomonas maltophilia: a closer look at institutional data amid CLSI breakpoint revisions.}, journal = {European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology}, volume = {44}, number = {2}, pages = {459-460}, doi = {10.1007/s10096-024-04995-5}, pmid = {39565466}, issn = {1435-4373}, mesh = {*Stenotrophomonas maltophilia/drug effects/isolation & purification ; *Anti-Bacterial Agents/pharmacology ; *Minocycline/pharmacology ; Humans ; Microbial Sensitivity Tests/standards ; Gram-Negative Bacterial Infections/microbiology/drug therapy ; }, abstract = {In this letter we respond Bakthavatchalam et al's brief report on susceptibility of Stenotrophomonas maltophilia to Minocycline in the setting of new susceptibility breakpoints. We outline our institution's experience with this organism and new data of susceptibility with the breakpoint of < 1 mg/L from the past 5 months showing 93.8% of 144 isolates remained susceptible.}, } @article {pmid39564190, year = {2024}, author = {Cavaliere, F and Hermann, DM and Magliaro, C}, title = {Editorial: Human brain organoids to model neurodegenerative diseases at the BOSS23 Brain Organoid Summer School.}, journal = {Frontiers in cellular neuroscience}, volume = {18}, number = {}, pages = {1501036}, doi = {10.3389/fncel.2024.1501036}, pmid = {39564190}, issn = {1662-5102}, } @article {pmid39564171, year = {2024}, author = {Byeon, H}, title = {Holistic approaches to mitigating psychological distress in gynecological cancer patients.}, journal = {World journal of psychiatry}, volume = {14}, number = {11}, pages = {1766-1771}, pmid = {39564171}, issn = {2220-3206}, abstract = {This article delves into the psychological impact of gynecological malignancies and suggests pathways to improve the quality of life (QoL) for affected patients. Building on Shang et al's comprehensive analysis, this piece integrates insights from various studies to highlight the profound influence of psychological and physical symptoms on patients undergoing treatment for gynecological cancers. The study underscores that anxiety and depression significantly exacerbate the disease's toll. Factors such as physical exercise and digital and interactive health interventions show promise in mitigating these adverse effects. The article emphasizes the necessity for a holistic care approach that addresses both physical and emotional needs. Recommendations include enhanced training for healthcare providers, public awareness campaigns, streamlined diagnostic pathways, and improved access to specialist care. These integrated strategies aim to ensure that women facing gynecological cancers can maintain an optimal QoL through comprehensive and multidisciplinary care models.}, } @article {pmid39563746, year = {2024}, author = {Moyana, TN}, title = {Metabolic dysfunction-associated steatotic liver disease: The question of long-term high-normal alanine aminotransferase as a screening test.}, journal = {World journal of gastroenterology}, volume = {30}, number = {42}, pages = {4576-4582}, pmid = {39563746}, issn = {2219-2840}, mesh = {Humans ; *Alanine Transaminase/blood ; *Biomarkers/blood ; Mass Screening/methods/standards ; Fatty Liver/diagnosis/blood/epidemiology ; Obesity/complications/diagnosis/epidemiology ; Early Diagnosis ; Reference Values ; Male ; Liver/pathology ; Non-alcoholic Fatty Liver Disease/diagnosis/blood/epidemiology ; }, abstract = {The growing prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) is being driven by the obesity epidemic. The quest for solutions continues particularly with regard to early detection. This editorial comments on the utility of long-term high-normal alanine aminotransferase (ALT) in screening for MASLD. Chen et al found that new onset MASLD can be detected by repetitively high normal ALT. Implicit in this concept is the question of what should be the accepted upper limit of normal (ULN) for ALT. It was previously set at 40 IU/L based on studies that included people with subclinical liver disease but the new consensus is 30/19 U/L in healthy males/females. Thus, when Chen et al defines the ULN as 40 U/L, others may view it as excessively high. It is important to recognize the variables affecting ULN e.g. instrumentation, diurnal variations, exercise and ageing. These variables matter when the distinctions are subtle e.g. normal vs high-normal. In this regard, the utility of long-term high normal ALT as a disease marker could be enhanced by combining it with other biomarkers, imaging and MASLD genetics to create machine learning classifiers. All in all, Chen et al's work on long-term high normal ALT as a marker of new-onset MASLD deserves merit.}, } @article {pmid39563026, year = {2025}, author = {Hawley, ZCE and Pardo, ID and Cao, S and Zavodszky, MI and Casey, F and Ferber, K and Luo, Y and Hana, S and Chen, SK and Doherty, J and Costa, R and Cullen, P and Liu, Y and Carlile, TM and Chowdhury, T and Doyle, B and Clarner, P and Mangaudis, K and Guilmette, E and Bourque, S and Koske, D and Nadella, MVP and Trapa, P and Hawes, ML and Raitcheva, D and Lo, SC}, title = {Dorsal root ganglion toxicity after AAV intra-CSF delivery of a RNAi expression construct into non-human primates and mice.}, journal = {Molecular therapy : the journal of the American Society of Gene Therapy}, volume = {33}, number = {1}, pages = {215-234}, pmid = {39563026}, issn = {1525-0024}, mesh = {Animals ; *Dependovirus/genetics ; Mice ; *MicroRNAs/genetics ; *Ganglia, Spinal/metabolism ; *Genetic Vectors/administration & dosage/genetics ; *RNA Interference ; Superoxide Dismutase-1/genetics ; Humans ; Neurons/metabolism ; Male ; }, abstract = {Dorsal root ganglion (DRG) toxicity has been consistently reported as a potential safety concern after delivery of adeno-associated viruses (AAVs) containing gene-replacement vectors but has yet to be reported for RNAi-based vectors. Here, we report DRG toxicity after AAV intra-CSF delivery of an RNAi expression construct-artificial microRNA targeting superoxide dismutase 1 (SOD1)-in non-human primates (NHPs) and provide evidence that this can be recapitulated within mice. Histopathology evaluation showed that NHPs and mice develop DRG toxicity after AAV delivery, including DRG neuron degeneration and necrosis and nerve-fiber degeneration that were associated with increases in cerebrospinal fluid (CSF) and serum phosphorylated neurofilament heavy chain (pNF-H). RNA-sequencing analysis of DRGs showed that dysregulated pathways were preserved between NHPs and mice, including increases in innate/adaptive immune responses and decreases in mitochondrial- and neuronal-related genes, following AAV treatment. Finally, endogenous miR-21-5p was upregulated in DRGs of AAV-treated NHPs and mice. Increases in miR-21-5p were also identified within the CSF of NHPs, which significantly correlated with pNF-H, implicating miR-21-5p as a potential biomarker of DRG toxicity in conjunction with other molecular analytes. This work highlights the importance of assessing safety concerns related to DRG toxicity when developing RNAi-based AAV vectors for therapeutic purposes.}, } @article {pmid39562997, year = {2024}, author = {Zheng, W and Xia, T and Zhang, X and Han, J and Li, Y and Tian, N and Zheng, G and Wang, J and Peng, Y and Yao, D and Long, F}, title = {Tailoring Multifunctional Amine Salts Based on Anisole Liquid Soaking for Fabricating Efficient and Stable Perovskite Solar Cells.}, journal = {ACS applied materials & interfaces}, volume = {16}, number = {48}, pages = {66643-66654}, doi = {10.1021/acsami.4c12455}, pmid = {39562997}, issn = {1944-8252}, abstract = {The post-treatment based on spin-coating (SC) organic amine salts is commonly used for surface modification of perovskite films to eliminate defects. However, there is still a lack of systematic study and a unified understanding of the functions and mechanisms of different organic amine salts. The SC method is also not conducive to the industrialization of solar cells. In this work, we study three different organic amine salts, and a passivation strategy for perovskite films based on green anisole liquid soaking (ALS) has been developed. Phenylethylammonium iodide (PEAI), diethylamine hydroiodide (DEAI), and guanidine hydroiodide (GAI) organic amine salt passivators are selected to modify perovskite films, and their effect and working mechanism are also systematically estimated. It is found that PEAI passivates shallow-level defects on the surface of perovskite films, while DEAI incorporates into the perovskite lattice to suppress point defects, and GAI eliminates excess PbI2 residuals in perovskite films. These three organic-amine-salt-modified devices achieve enhanced power conversion efficiencies (PCE) of 21.82% (PEAI-ALS), 21.74% (DEAI-ALS), and 22.21% (GAI-ALS), which is much higher than that of the pristine device without treatment (19.95%). The PCE of the PEAI-ALS device retains nearly 94% of the initial efficiency after 1200 h in unpackaged conditions and about 40% ambient humidity, achieving the best stability performance. Particularly, the PEAI-ALS device has the best comprehensive performance in efficiency and stability. And PEAI is estimated by the SC method and ALS method, and it is found that the PEAI-ALS device achieves a higher PCE compared to the PEAI-SC device (21.51%). We believe that the post-treatment based on a combination of appropriate amine salts and ALS enables a universal approach for fabrication of perovskite solar cells with enhanced photovoltaic performance.}, } @article {pmid39562594, year = {2024}, author = {Tahmasebi, BK and Zand, E and Yousefi, A and Babaei, S and Sadeghpour, A}, title = {Surveillance and mapping of tribenuron-methyl-resistant weeds in wheat fields.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {28626}, pmid = {39562594}, issn = {2045-2322}, mesh = {*Plant Weeds/drug effects ; *Triticum/drug effects/genetics/growth & development ; *Herbicide Resistance/genetics ; *Herbicides/pharmacology ; *Arylsulfonates/pharmacology ; Iran ; Weed Control/methods ; }, abstract = {Tribenuron-methyl (TBM) is among the herbicides that are widely used for controlling broadleaf weeds in wheat fields in Iran due to its low mammalian toxicity and environmental risk, use at low doses, the broad spectrum of weed control, and low price compared to other herbicides. However, wheat farmers' repeated application and dissatisfaction with the optimal and effective control of the TBM herbicide have led to investigating broadleaf weed resistance in Iranian wheat fields. For this purpose, through a national call in 2018, a total of 240 broadleaf weed populations belonging to 13 species and 7 plant families were collected from 153 wheat fields in 72 counties across 14 provinces suspected to be resistant to the TBM herbicide. Then, a screening test was conducted in a completely randomized design with 5 replications of each biotype using the recommended dose of 25 g a.i. ha[- 1] of TBM in the greenhouse. Overall, the results indicated that 124 (51.7%) of the screened populations were resisted to TBM. Specifically, 44 populations (81%) of Sinapis arvensis L., 18 populations (45%) of Malva neglecta Wallr., 25 populations (45%) of Silybum marianum (L.) Gaertn, 2 populations (66.6%) of Ammi majus L., 1 population (50%) of Rapistrum rugosum L., 3 populations (21%) of Descurainia Sophia (L.) Webb ex Prantl, 9 populations (36%) of Vaccaria hispanica Mill., 8 populations (48%) of Galium aparine L., 9 populations (75%) of Melilotus indicus L. According to the Adkins and Maas evaluation, 4 populations (100%) of Raphanus raphanistrum L. were classified as resistant to TBM. This study is the first comprehensive investigation of broadleaf weed resistance to TBM across Iranian wheat fields, providing crucial insights for future herbicide management strategies. Given the high incidence of resistance, continued use of TBM in Iranian wheat fields may lead to increased yield loss and environmental pollution. Additionally, it is necessary to investigate cross-resistance in resistant populations to other ALS-inhibiting herbicides.}, } @article {pmid39561111, year = {2024}, author = {Rohrer, C and Palumbo, A and Paul, M and Reese, E and Basu, S}, title = {Neurotransmitters and neural hormone-based probes for quadruplex DNA sequences associated with neurodegenerative diseases.}, journal = {Nucleosides, nucleotides & nucleic acids}, volume = {}, number = {}, pages = {1-24}, doi = {10.1080/15257770.2024.2431145}, pmid = {39561111}, issn = {1532-2335}, abstract = {The potential of neurotransmitters and neural hormones as possible G-quadruplex DNA binders was analyzed using fluorescence spectroscopy, surface-enhanced Raman spectroscopy (SERS), DNA melting analysis, and molecular docking. G-quadruplex sequences, (GGC)3 and G4C2, with roles in Fragile X syndrome and amyotrophic lateral sclerosis (ALS), respectively, were selected, and their interactions with melatonin, serotonin, and gamma-aminobutyric acid (GABA), were studied. Both melatonin and serotonin demonstrated strong interactions with the DNA sequences with hydrogen bonding being the primary mode of interaction, with some non-intercalative interactions involving the π systems. GABA demonstrated much weaker interactions and may not be a suitable candidate as a probe for low concentrations of G-quadruplex DNA.}, } @article {pmid39560839, year = {2024}, author = {Wu, R and Ramakrishnan, S and Lin, H and Dong, Z and Liu, M and Qiang, L}, title = {Development and validation a novel FEZF2 based fluorescent reporter for corticospinal motor neurons.}, journal = {Metabolic brain disease}, volume = {40}, number = {1}, pages = {17}, pmid = {39560839}, issn = {1573-7365}, support = {R01 NS115977/NS/NINDS NIH HHS/United States ; 4100083087//the CURE program via Drexel University College of Medicine/ ; 32070725//the National Natural Science Foundation/ ; }, mesh = {Animals ; *Motor Neurons/metabolism ; Mice ; Nerve Tissue Proteins/genetics/metabolism ; Pyramidal Tracts/metabolism ; Green Fluorescent Proteins/genetics/metabolism ; Genes, Reporter ; Cells, Cultured ; DNA-Binding Proteins ; }, abstract = {Corticospinal motor neurons (CSMNs), also named upper motor neurons, are the giant pyramidal neurons called Betz cells. In mammals, the majority of CSMNs reside within layer V of the primary motor cortex, where they extend long axon bundles named the pyramidal tract into the brainstem and the spinal cord to control voluntary movement. CSMN lesions are implicated in a variety of neurodegenerative disorders, such Amyotrophic Lateral Sclerosis, Primary Lateral Sclerosis and Hereditary Spastic paraplegia. Although FEZF2-CTIP2 genetic axis have been indicated as the cardinal molecular pathway underlying the development of CSMNs, these proteins are transcription factors that are mostly used to label the nuclei of CSMNs in the fixed cells and tissues. Therefore, a fluorescent reporter to mark CSMNs will be invaluable in identifying living CSMNs, including their extended processes, for time-lapse imaging and high-throughput molecular analyses with much more improved specificity. Based on the in-silico analysis, we identified a putative region within the promoter sequence of FEZF2 and assembled it with an indispensable enhancer motif at its downstream of the gene to form a complex promoter that drives the expression of reporter GFP. The plasmid and virus of FEZF2:eGFP reporter constructs were further validated for its use in specifically labeling CSMNs in primary neuronal cultures from the embryonic rat motor cortex, postnatal mouse cortex. This innovative molecular labeling tool has the potential to offer indispensable support in diverse experimental setups, enabling a comprehensive understanding of the susceptibility and specificity of CSMNs in a wide array of neurological disorders.}, } @article {pmid39559551, year = {2024}, author = {Wang, J and Chi, L and Liu, S and Yin, J and Zhang, Y and Shen, J and Wang, X}, title = {Overlooked role of long capping time and environmental factors in the plateau lake for impairing lanthanum-modified-bentonite's immobilization to phosphate.}, journal = {Water research X}, volume = {25}, number = {}, pages = {100272}, pmid = {39559551}, issn = {2589-9147}, abstract = {Lanthanum-modified-bentonite(LMB) has been applied for eutrophication management as a phosphate(P)-binding agent in many lakes. However, re-eutrophication took place several years or decades later after the first practice of capping due to dynamic environmental factors in the plateau lake. Here, we investigated the effect of long-term capping and integrated environmental factors in the plateau lake including alkalinity, organic matter, disturbance and photodegradation to the LMB immobilization. Long-term LMB immobilization exhibited C accumulation(82.3%), La depletion(53.5%) and lager size effect in the sediment particle, indicating the breakage of La-O-P bonds and the formation of La-O-C bonds over immobilization time. Additionally, pH(8-10) in the plateau lake could enhance the P desorption and decrease P adsorption through electrostatic repulsion enhancement with the zeta potential reduction(7.2 mV). Further disturbance experiment indicated a significant releasing trend of active P and DGT-labile P from the solid phase, pore water to the overlying water after disturbances due to resuspended releasing, particle size and amorphous Fe, Mn and Al's redistribution. Moreover, [31]P NMR and EPR results indicated photodegradation after disturbance converted diester phosphate into orthophosphate with long-term LMB immobilization via the oxidation of ·OH in the sediment of the plateau lake. Therefore, management issues for Xingyun Lake may apply to other plateau lakes with low external P input, intermediate depth and intense disturbance.}, } @article {pmid39558635, year = {2024}, author = {Pillai, M and Patil, AD and Das, A and Jha, SK}, title = {Pathological Mutations D169G and P112H Electrostatically Aggravate the Amyloidogenicity of the Functional Domain of TDP-43.}, journal = {ACS chemical neuroscience}, volume = {15}, number = {23}, pages = {4267-4283}, doi = {10.1021/acschemneuro.4c00372}, pmid = {39558635}, issn = {1948-7193}, mesh = {Humans ; *DNA-Binding Proteins/genetics/metabolism/chemistry ; *Static Electricity ; *Amyloid/metabolism/genetics ; Mutation ; Protein Domains/genetics ; Hydrogen-Ion Concentration ; Protein Aggregation, Pathological/genetics/metabolism ; }, abstract = {Aggregation of TDP-43 is linked to the pathogenesis of many neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). Notably, electrostatic point mutations such as D169G and P112H, located within the highly conserved functional tandem RNA recognition motif (RRM) domains of the TDP-43 protein (TDP-43[tRRM]), have been identified in diseased patients as well. In this study, we address how the electrostatic mutations alter both the native state stability and aggregation propensity of TDP-43[tRRM]. The mutants D169G and P112H show increased chemical stability compared to the TDP-43[tRRM] at physiological pH. However, at low pH, both the mutants undergo a conformational change to form amyloid-like fibrils, though with variable rates─the P112H mutant being substantially faster than the other two sequences (TDP-43[tRRM] and D169G mutant) showing comparable rates. Moreover, among the three sequences, only the P112H mutant undergoes a strong ionic strength-dependent aggregability trend. These observations signify the substantial contribution of the excess charge of the P112H mutant to its unique aggregation process. Complementary simulated observables with atomistic resolution assign the experimentally observed sequence-, pH-, and ionic strength-dependent aggregability pattern to the degree of thermal lability of the mutation site-containing RRM1 domain and its extent of dynamical anticorrelation with the RRM2 domain whose combination eventually dictate the extent of generation of aggregation-prone partially unfolded conformational ensembles. Our choice of a specific charge-modulated pathogenic mutation-based experiment-simulation-combination approach unravels the otherwise hidden residue-wise contribution to the individual steps of this extremely complicated multistep aggregation process.}, } @article {pmid39557859, year = {2024}, author = {Pamphlett, R and Parkin Kullmann, J}, title = {Early life events may be the first steps on the multistep path to amyotrophic lateral sclerosis.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {28497}, pmid = {39557859}, issn = {2045-2322}, mesh = {*Amyotrophic Lateral Sclerosis/epidemiology/etiology/genetics ; Humans ; Female ; Male ; Middle Aged ; Risk Factors ; Adult ; Aged ; Case-Control Studies ; Surveys and Questionnaires ; }, abstract = {A combination of multiple genetic and environmental factors appear to be required to trigger the onset of amyotrophic lateral sclerosis (ALS). Early life environmental exposures have been reported to be risk factors for a variety of adult-onset diseases, so we used data from an online international ALS case-control questionnaire to estimate whether any of these could be risk factors for the clinical onset of ALS. Responses were obtained from 1,049 people aged 40 years or more, 568 with ALS and 481 controls. People with ALS were more likely to have been born and lived longer in a country area than in a city area, to have younger parents, and to have lower educational attainment and fewer years of education. No ALS-control differences were found in sibling numbers, birth order, adult height, birth weight, parent smoking, Cesarean delivery, or age of starting smoking. In conclusion, early life events and conditions may be part of a group of polyenvironmental risk factors that act together with polygenetic variants to trigger the onset of ALS. Reducing exposure to adverse environmental factors in early life could help to lower the risk of later developing ALS.}, } @article {pmid39557152, year = {2025}, author = {Yu, H and Ren, K and Jin, Y and Zhang, L and Liu, H and Huang, Z and Zhang, Z and Chen, X and Yang, Y and Wei, Z}, title = {Mitochondrial DAMPs: Key mediators in neuroinflammation and neurodegenerative disease pathogenesis.}, journal = {Neuropharmacology}, volume = {264}, number = {}, pages = {110217}, doi = {10.1016/j.neuropharm.2024.110217}, pmid = {39557152}, issn = {1873-7064}, mesh = {Humans ; *Neurodegenerative Diseases/metabolism/pathology/immunology ; *Neuroinflammatory Diseases/metabolism/immunology/pathology ; Animals ; *Mitochondria/metabolism ; *Alarmins/metabolism ; Inflammasomes/metabolism ; DNA, Mitochondrial/metabolism ; Reactive Oxygen Species/metabolism ; }, abstract = {Neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS) are increasingly linked to mitochondrial dysfunction and neuroinflammation. Central to this link are mitochondrial damage-associated molecular patterns (mtDAMPs), including mitochondrial DNA, ATP, and reactive oxygen species, released during mitochondrial stress or damage. These mtDAMPs activate inflammatory pathways, such as the NLRP3 inflammasome and cGAS-STING, contributing to the progression of neurodegenerative diseases. This review delves into the mechanisms by which mtDAMPs drive neuroinflammation and discusses potential therapeutic strategies targeting these pathways to mitigate neurodegeneration. Additionally, it explores the cross-talk between mitochondria and the immune system, highlighting the complex interplay that exacerbates neuronal damage. Understanding the role of mtDAMPs could pave the way for novel treatments aimed at modulating neuroinflammation and slowing disease progression, ultimately improving patient outcome.}, } @article {pmid39556975, year = {2024}, author = {Yu, Z and Qi, J and Liu, S and Zhao, X and Huang, H}, title = {Evaluating forest aboveground biomass estimation model using simulated ALS point cloud from an individual-based forest model and 3D radiative transfer model across continents.}, journal = {Journal of environmental management}, volume = {372}, number = {}, pages = {123287}, doi = {10.1016/j.jenvman.2024.123287}, pmid = {39556975}, issn = {1095-8630}, mesh = {*Biomass ; *Forests ; Models, Theoretical ; Computer Simulation ; Trees/growth & development ; Algorithms ; }, abstract = {Area-based approach (ABA) has been widely employed for estimating forest aboveground biomass (AGB) using airborne laser scanning (ALS) data. However, its scalability is limited due to challenges in model generalization across different forest types and regions. The selection of sensitive variables from ALS data is crucial for constructing robust forest AGB estimation models, yet this selection varies significantly among forest types and regions. Traditionally, assessing the influence of variable selection is hindered by the lack of accurate reference forest AGB values. Computer simulation-based method provides a perspective for exploring these challenges. This study employs an individual-based forest growth process model, FORMIND, coupled with a 3D radiative transfer model (RTM), LESS, to evaluate the transferability of ABA-based forest AGB estimation models and the generalization of ALS-derived variables. We used six virtual 3D forest scenes and two real-world forest sites, representing a range of global forest types, along with their simulated ALS data, to develop a forest AGB estimation model using the random forest algorithm, which allowed us to analyze the importance of various variables. We assessed model transferability through cross-comparison. Additionally, we validated the model using field plots and ALS data collected from two distinct regions. The results showed that the canopy surface area and volume extracted using the α-shape algorithm and parameters fitted from the Weibull distribution are vital variables when using ALS for forest AGB estimation across forest types and regions. Incorporating these variables into the model significantly improves the accuracy of forest AGB estimation. The optimized model achieved a R[2] of 0.945, a RMSE of 34.22 t/ha, and a MAE of 20.53 t/ha. Our study not only deepens the understanding of the relationship between forest vertical structural metrics and AGB but also highlights the potential of computer simulation as a tool for refining the estimation of forest structural parameters.}, } @article {pmid39556393, year = {2024}, author = {Ishii, J and Nishikimi, M and Kikutani, K and Ohki, S and Ota, K and Anzai, T and Takahashi, K and Okubo, M and Ohshimo, S and Iwami, T and Shime, N}, title = {Resuscitation Attempt and Outcomes in Patients With Asystole Out-of-Hospital Cardiac Arrest.}, journal = {JAMA network open}, volume = {7}, number = {11}, pages = {e2445543}, pmid = {39556393}, issn = {2574-3805}, mesh = {Humans ; *Out-of-Hospital Cardiac Arrest/therapy/mortality/epidemiology ; Male ; Female ; Aged ; Middle Aged ; Japan/epidemiology ; *Cardiopulmonary Resuscitation/methods ; *Registries ; *Emergency Medical Services/statistics & numerical data ; Aged, 80 and over ; Advanced Cardiac Life Support/methods ; Prospective Studies ; Epinephrine/therapeutic use/administration & dosage ; Treatment Outcome ; Cohort Studies ; }, abstract = {IMPORTANCE: Little is known about the epidemiology of out-of-hospital cardiac arrest (OHCA) in patients with asystole in countries where prehospital resuscitation is not withheld or terminated.

OBJECTIVE: To investigate the secular trends in the patient outcomes and advanced life support (ALS) procedures and evaluate the association of ALS procedures with favorable outcomes among patients with OHCA and asystole.

This cohort study analyzed data from a nationwide prospective OHCA registry in Japan. OHCA occurred from June 1, 2014, to December 31, 2020. Adults with an initial rhythm of asystole and OHCA were included in the analysis, which was conducted between July 29, 2022, and August 24, 2024.

EXPOSURES: Year of OHCA and prehospital ALS procedures (advanced airway management [AAM] and intravenous epinephrine administration).

MAIN OUTCOMES AND MEASURES: Trends in prehospital and in-hospital ALS procedures and patient outcomes were described using the Jonckheere-Terpstra trend test for continuous variables and the Cochran-Armitage trend test for categorical variables. The primary outcome was a favorable neurological outcome at 30 days. The secondary outcomes included a favorable neurological outcome at 90 days and survival at 30 and 90 days. Associations between prehospital procedures and outcomes were analyzed using time-dependent propensity score and risk-set matching.

RESULTS: Of 60 349 patients with OHCA, 35 843 (59.4%) presented with asystole (median age, 77 [IQR, 64-85] years; 20 573 [57.4%] men). Among these, 33 674 patients (93.9%) underwent ALS procedures, with 67 (0.2%) achieving a favorable neurological outcome at 30 days. No significant trends in the outcomes were noted, except for a decline in return of spontaneous circulation (424 of 1848 [22.9%] to 1178 of 5892 [20.0%]; P = .003). Neither AAM (odds ratio [OR], 1.27 [95% CI, 0.76-2.12]; P = .36) nor intravenous epinephrine administration (OR, 0.53 [95% CI, 0.24-1.13]; P = .10) was associated with a favorable neurological outcome at 30 days, although both were associated with survival at 30 days (ORs, 1.45 [95% CI, 1.21-1.74] and 1.81 [95% CI, 1.44-2.27], respectively; P < .001 for both).

CONCLUSIONS AND RELEVANCE: In this cohort study of patients with OHCA presenting with asystole, the proportion with a favorable neurological outcome at 30 days was substantially low, and no prehospital ALS procedure was associated with a favorable neurological outcome. These findings suggest that discussions regarding implementation of a termination of resuscitation rule for such patients are warranted.}, } @article {pmid39556113, year = {2025}, author = {Yeganeh Markid, T and Pourahmadiyan, A and Hamzeh, S and Sharifi-Bonab, M and Asadi, MR and Jalaiei, A and Rezazadeh, M and Ghafouri-Fard, S}, title = {A special focus on polyadenylation and alternative polyadenylation in neurodegenerative diseases: A systematic review.}, journal = {Journal of neurochemistry}, volume = {169}, number = {2}, pages = {e16255}, doi = {10.1111/jnc.16255}, pmid = {39556113}, issn = {1471-4159}, mesh = {Humans ; *Neurodegenerative Diseases/genetics/metabolism ; *Polyadenylation/physiology ; Animals ; }, abstract = {Neurodegenerative diseases (NDDs) are one of the prevailing conditions characterized by progressive neuronal loss. Polyadenylation (PA) and alternative polyadenylation (APA) are the two main post-transcriptional events that regulate neuronal gene expression and protein production. This systematic review analyzed the available literature on the role of PA and APA in NDDs, with an emphasis on their contributions to disease development. A comprehensive literature search was performed using the PubMed, Scopus, Cochrane, Google Scholar, Embase, Web of Science, and ProQuest databases. The search strategy was developed based on the framework introduced by Arksey and O'Malley and supplemented by the inclusion and exclusion criteria. The study selection was performed by two independent reviewers. Extraction and data organization were performed in accordance with the predefined variables. Subsequently, quantitative and qualitative analyses were performed. Forty-seven studies were included, related to a variety of NDDs, namely Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. Disease induction was performed using different models, including human tissues, animal models, and cultured cells. Most investigations were related to PA, although some were related to APA or both. Amyloid precursor protein (APP), Tau, SNCA, and STMN2 were the major genes identified; most of the altered PA patterns were related to mRNA stability and translation efficiency. This review particularly underscores the key roles of PA and APA in the pathogenesis of NDDs through their mechanisms that contribute to gene expression dysregulation, protein aggregation, and neuronal dysfunction. Insights into these mechanisms may lead to new therapeutic strategies focused on the modulation of PA and APA activities. Further research is required to investigate the translational potential of targeting these pathways for NDD treatment.}, } @article {pmid39553255, year = {2024}, author = {Zeinali, M and Almasi Dooghaee, M and Ziaee, M and Haghi Ashtiani, B}, title = {Evaluation of Relationship Between Laboratory, Electrodiagnostic, and Functional Parameters in Patients With Amyotrophic Lateral Sclerosis; A Cross Sectional Study.}, journal = {Basic and clinical neuroscience}, volume = {15}, number = {4}, pages = {553-560}, pmid = {39553255}, issn = {2008-126X}, abstract = {INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is an adult-onset motor neuron disease with a poor prognosis that leads to limb and or bulbar muscle degeneration. Several demographic and biological factors have prognostic importance, but little data exist on the relationship between clinical, electrodiagnostic, and laboratory markers as predictors of disease progression. We aimed to assess the relationships between different aspects of ALS patients' clinical, electrodiagnostic, and laboratory features and their level of functioning.

METHODS: We included 27 ALS patients diagnosed within the last two years. A neurology resident conducted clinical assessment and electrodiagnostic studies. The motor unit number index (MUNIX) and compound motor action potential (CMAP) were used to measure motor unit loss. Serum creatinine, urea, albumin, and creatine kinase were measured as laboratory markers. We used the Persian version of the ALS functional rating scale (ALS-FRS) as the main outcome measure. The Pearson correlation coefficient was calculated to assess the correlations using the SPSS software, version 16.

RESULTS: None of the demographic or laboratory parameters were correlated with ALSFRS. Patients with the onset of disease in the limbs had a higher MUNIX score than those with bulbar onset. Also, increased body mass index (BMI) was associated with lower CMAP and MUNIX scores (P=0.02). Higher serum creatinine levels were significantly associated with higher lower limb MUNIX (P=0.04). Higher lower limb MUNIX was associated with a higher lower limb functional score.

CONCLUSION: Decreased serum creatinine may indicate lower limb motor unit loss in patients with ALS. Also, MUNIX scores may be used as substitutes for ALS-FRS in ALS trials. Further research is needed to elucidate the clinical application of these findings.}, } @article {pmid39552508, year = {2025}, author = {Zhong, R and Dionela, DLA and Kim, NH and Harris, EN and Geisler, JG and Wei-LaPierre, L}, title = {Micro-Doses of DNP Preserve Motor and Muscle Function with a Period of Functional Recovery in Amyotrophic Lateral Sclerosis Mice.}, journal = {Annals of neurology}, volume = {97}, number = {3}, pages = {542-557}, pmid = {39552508}, issn = {1531-8249}, support = {R56 NS117429/NS/NINDS NIH HHS/United States ; NS99545/NS/NINDS NIH HHS/United States ; R01 NS127858/NS/NINDS NIH HHS/United States ; R21 NS099545/NS/NINDS NIH HHS/United States ; NS117429/NS/NINDS NIH HHS/United States ; NS127858/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; *Amyotrophic Lateral Sclerosis/drug therapy/physiopathology/genetics ; *2,4-Dinitrophenol/pharmacology/administration & dosage/therapeutic use ; Mice ; *Muscle, Skeletal/drug effects/physiopathology ; Mice, Transgenic ; *Recovery of Function/drug effects ; Disease Models, Animal ; Muscle Contraction/drug effects ; *Uncoupling Agents/pharmacology/administration & dosage ; Male ; Neuromuscular Junction/drug effects ; }, abstract = {OBJECTIVE: Mitochondrial dysfunction is one of the earliest pathological events observed in amyotrophic lateral sclerosis (ALS). The aim of this study is to evaluate the therapeutic efficacy of 2,4-dinitrophenol (DNP), a mild mitochondrial uncoupler, in an ALS mouse model to provide preclinical proof-of-concept evidence of using DNP as a potential therapeutic drug for ALS.

METHODS: hSOD1[G93A] mice were treated with 0.5-1.0 mg/kg DNP through daily oral gavage from presymptomatic stage or disease onset until 18 weeks old. Longitudinal behavioral studies were performed weekly or biweekly from 6 to 18 weeks old. In situ muscle contraction measurements in extensor digitorum longus muscles were conducted to evaluate the preservation of contractile force and motor unit numbers in hSOD1[G93A] mice following DNP treatment. Muscle innervation and inflammatory markers were assessed using immunostaining. Extent of protein oxidation and activation of Akt pathway were also examined.

RESULTS: DNP delayed disease onset; improved motor coordination and muscle performance in vivo; preserved muscle contractile function, neuromuscular junction morphology, and muscle innervation; and reduced inflammation and protein oxidation at 18 weeks old in hSOD1[G93A] mice. Strikingly, symptomatic hSOD1[G93A] mice exhibited a period of recovery in running ability at 20 cm/s several weeks after 2,4-dinitrophenol treatment started at disease onset, offering the first observation in disease phenotype reversal using a small molecule.

INTERPRETATION: Our results strongly support that micro-dose DNP may be used as a potential novel treatment for ALS patients, with a possibility for recovery, when used at optimal doses and time of intervention. ANN NEUROL 2025;97:542-557.}, } @article {pmid39552337, year = {2024}, author = {Baindoor, S and Gibriel, HAY and Venø, MT and Su, J and Morrissey, EP and Jirström, E and Woods, I and Kenny, A and Alves, M and Halang, L and Fabbrizio, P and Bilen, M and Engel, T and Hogg, MC and Bendotti, C and Nardo, G and Slack, RS and Kjems, J and Prehn, JHM}, title = {Distinct fingerprints of tRNA-derived small non-coding RNA in animal models of neurodegeneration.}, journal = {Disease models & mechanisms}, volume = {17}, number = {11}, pages = {}, pmid = {39552337}, issn = {1754-8411}, support = {17/JPND/3455//Research Ireland/ ; //European Regional Development Fund/ ; //FutureNeuro/ ; //Precision ALS/ ; 18/CRT/6214//Research Ireland Centre for Research Training in Genomics Data Science/ ; //EU Joint Programme - Neurodegenerative Disease Research/ ; CUP E48I20000000007//Regione Lombardia/ ; SG-2018-12366226//Ministero della Salute/ ; //Royal College of Surgeons in Ireland/ ; }, mesh = {Animals ; *Disease Models, Animal ; *RNA, Transfer/genetics/metabolism ; *RNA, Small Untranslated/genetics ; Amyotrophic Lateral Sclerosis/genetics/pathology ; Neurodegenerative Diseases/genetics/pathology ; Mice ; Humans ; Mice, Transgenic ; Parkinson Disease/genetics/pathology ; Frontotemporal Dementia/genetics/pathology ; }, abstract = {Transfer RNA-derived small RNAs (tsRNAs) - categorized as tRNA-derived fragments (tRFs), tRNA-derived stress-induced RNAs (tiRNAs) and internal tRF (itRF) - are small non-coding RNAs that participate in various cellular processes such as translation inhibition and responses to cellular stress. We here identified tsRNA profiles within susceptible tissues in animal models of amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD) and Parkinson's disease (PD) to pinpoint disease-specific tsRNAs and those shared across neurodegenerative diseases. We performed small RNA sequencing in the SOD1G93A and TDP43A315T mouse models of ALS (spinal cord), the TauP301S model of FTD (hippocampus), and the parkin/POLG model of PD (substantia nigra). Bioinformatic analysis showed higher expression of 5' tiRNAs selectively in the two ALS models, lower expression of 3' tRFs in both the ALS and FTD mouse models, and lower expression of itRF Arg in the PD model. Experimental validation confirmed the expression of tsRNAs. Gene Ontology analysis of targets associated with validated 3' tRFs indicated functions in the regulation of synaptic and neuronal pathways. Our profiling of tsRNAs indicates disease-specific fingerprints in animal models of neurodegeneration, which require validation in human disease.}, } @article {pmid39551788, year = {2024}, author = {Sadeghdoust, M and Das, A and Kaushik, DK}, title = {Fueling neurodegeneration: metabolic insights into microglia functions.}, journal = {Journal of neuroinflammation}, volume = {21}, number = {1}, pages = {300}, pmid = {39551788}, issn = {1742-2094}, support = {MS220110//U.S. Department of Defense/ ; 916184//Multiple Sclerosis Society of Canada/ ; }, mesh = {*Microglia/metabolism/pathology ; Humans ; *Neurodegenerative Diseases/metabolism/pathology ; Animals ; }, abstract = {Microglia, the resident immune cells of the central nervous system, emerge in the brain during early embryonic development and persist throughout life. They play essential roles in brain homeostasis, and their dysfunction contributes to neuroinflammation and the progression of neurodegenerative diseases. Recent studies have uncovered an intricate relationship between microglia functions and metabolic processes, offering fresh perspectives on disease mechanisms and possible treatments. Despite these advancements, there are still significant gaps in our understanding of how metabolic dysregulation affects microglial phenotypes in these disorders. This review aims to address these gaps, laying the groundwork for future research on the topic. We specifically examine how metabolic shifts in microglia, such as the transition from oxidative phosphorylation and mitochondrial metabolism to heightened glycolysis during proinflammatory states, impact the disease progression in Alzheimer's disease, multiple sclerosis, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease. Additionally, we explore the role of iron, fatty and amino acid metabolism in microglial homeostasis and repair. Identifying both distinct and shared metabolic adaptations in microglia across neurodegenerative diseases could reveal common therapeutic targets and provide a deeper understanding of disease-specific mechanisms underlying multiple CNS disorders.}, } @article {pmid39551782, year = {2024}, author = {Labrador, L and Rodriguez, L and Beltran, S and Hernandez, F and Gomez, L and Ojeda, P and Bergmann, C and Calegaro-Nassif, M and Kerr, B and Medinas, DB and Manque, P and Woehlbier, U}, title = {Overexpression of autophagy enhancer PACER/RUBCNL in neurons accelerates disease in the SOD1[G93A] ALS mouse model.}, journal = {Biological research}, volume = {57}, number = {1}, pages = {86}, pmid = {39551782}, issn = {0717-6287}, support = {1200459//Agencia Nacional de Investigación y Desarrollo/ ; 1150743//Agencia Nacional de Investigación y Desarrollo/ ; 11160288//Agencia Nacional de Investigación y Desarrollo/ ; 1191538//Agencia Nacional de Investigación y Desarrollo/ ; 1230905//Agencia Nacional de Investigación y Desarrollo/ ; ACT210039//Agencia Nacional de Investigación y Desarrollo/ ; 11240328//Agencia Nacional de Investigación y Desarrollo/ ; 1240176//Agencia Nacional de Investigación y Desarrollo/ ; }, mesh = {Animals ; *Amyotrophic Lateral Sclerosis/genetics/pathology ; *Mice, Transgenic ; *Disease Models, Animal ; *Autophagy/genetics/physiology ; Mice ; Humans ; Superoxide Dismutase-1/genetics ; Motor Neurons/pathology ; Superoxide Dismutase/genetics ; Neurons/pathology ; Male ; Female ; Autophagy-Related Proteins/genetics/metabolism ; Disease Progression ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a debilitating and fatal paralytic disorder associated with motor neuron death. Mutant superoxide dismutase 1 (SOD1) misfolding and aggregation have been linked to familial ALS, with the accumulation of abnormal wild-type SOD1 species being also observed in postmortem tissue of sporadic ALS cases. Both wild-type and mutated SOD1 are reported to contribute to motoneuron cell death. The autophagic pathway has been shown to be dysregulated in ALS. Recent evidence suggests a dual time-dependent role of autophagy in the progression of the disease. PACER, also called RUBCNL (Rubicon-like), is an enhancer of autophagy and has been found diminished in its levels during ALS pathology in mice and humans. Pacer loss of function disturbs the autophagy process and leads to the accumulation of SOD1 aggregates, as well as sensitizes neurons to death. Therefore, here we investigated if constitutive overexpression of PACER in neurons since early development is beneficial in an in vivo model of ALS. We generated a transgenic mouse model overexpressing human PACER in neurons, which then was crossbred with the mutant SOD1[G93A] ALS mouse model. Unexpectedly, PACER/SOD1[G93A] double transgenic mice exhibited an earlier disease onset and shorter lifespan than did littermate SOD1[G93A] mice. The overexpression of PACER in neurons in vivo and in vitro increased the accumulation of SOD1 aggregates, possibly due to impaired autophagy. These results suggest that similar to Pacer loss-of function, Pacer gain-of function is detrimental to autophagy, increases SOD1 aggregation and worsens ALS pathogenesis. In a wider context, our results indicate the requirement to maintain a fine balance of PACER protein levels to sustain proteostasis.}, } @article {pmid39551156, year = {2025}, author = {Chen, LC and Martin, A and Senna, MM}, title = {Response to Truel J. et al's "Response to 'Topical tofacitinib for patients with lichen planopilaris and/or frontal fibrosing alopecia'".}, journal = {Journal of the American Academy of Dermatology}, volume = {92}, number = {3}, pages = {e69}, doi = {10.1016/j.jaad.2024.11.011}, pmid = {39551156}, issn = {1097-6787}, } @article {pmid39551139, year = {2024}, author = {Liu, C and Chen, IS and Barri, M and Murrell-Lagnado, R and Kubo, Y}, title = {Structural determinants of M2R involved in inhibition by Sigma-1R.}, journal = {The Journal of biological chemistry}, volume = {300}, number = {12}, pages = {108006}, pmid = {39551139}, issn = {1083-351X}, mesh = {*Receptors, sigma/metabolism/genetics ; Humans ; *Sigma-1 Receptor ; HEK293 Cells ; *Receptor, Muscarinic M2/metabolism/genetics ; Animals ; G Protein-Coupled Inwardly-Rectifying Potassium Channels/metabolism/genetics ; }, abstract = {Sigma-1 receptor (S1R) is a multimodal chaperone protein that is implicated in various pathophysiological conditions including drug addiction, Alzheimer's disease, and amyotrophic lateral sclerosis (ALS). S1R interacts with various ion channels and receptors on the endoplasmic reticulum or plasma membrane (PM). It has been reported that S1R colocalizes with the M2-muscarinic acetylcholine receptor (M2R) on the soma of motoneurons, although a functional interaction between these two proteins has not been established. Here, we investigated the regulation of M2R signaling by S1R using electrophysiological recordings of GIRK currents in HEK293T cells. We observed that S1R strongly inhibited M2R-mediated activation of GIRK1/2, but the disease mutant linked to ALS, S1R E102Q, did not. The inhibitory effect of S1R was selective for M2R and wasn't seen when S1R was co-expressed with other Gi/o coupled receptors including M4R. Chimeric and mutant receptors of M2R and M4R were generated and analyzed, and this highlighted Ala401 in the transmembrane 6 domain (TM6) of M2R and Glu172 as well as Glu175 in the extracellular loop 2 regions of M2R, as essential for the inhibition by S1R. Co-immunoprecipitation confirmed the physical interaction between M2R and S1R. Immunocytochemical labeling of M2R and S1R expressed in HeLa cells, HEK293T cells, and cultured hippocampal neurons, showed clear PM expression of M2R throughout the cell which was decreased by coexpression with S1R but was still apparent. Taken together, our results show that S1R interacts with M2R to reduce both its PM expression and function, and this involves TM6 and the extracellular loop 2.}, } @article {pmid39551138, year = {2024}, author = {Yang, C and Leifer, C and Lammerding, J and Hu, F}, title = {Regulation of TAR DNA binding protein 43 (TDP-43) homeostasis by cytosolic DNA accumulation.}, journal = {The Journal of biological chemistry}, volume = {300}, number = {12}, pages = {107999}, pmid = {39551138}, issn = {1083-351X}, support = {R21 AG078741/AG/NIA NIH HHS/United States ; }, mesh = {*DNA-Binding Proteins/metabolism/genetics ; *Cytosol/metabolism ; Humans ; Animals ; *Homeostasis ; DNA/metabolism ; Amyotrophic Lateral Sclerosis/metabolism/genetics/pathology ; Cytoplasm/metabolism ; beta Karyopherins/metabolism/genetics ; Neurons/metabolism/pathology ; Mice ; Cell Nucleus/metabolism ; Oligodeoxyribonucleotides/metabolism ; }, abstract = {TAR DNA-binding protein 43 (TDP-43) is a DNA/RNA binding protein predominantly localized in the nucleus under physiological conditions. TDP-43 proteinopathy, characterized by cytoplasmic aggregation and nuclear loss, is associated with many neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Thus it is crucial to understand the molecular mechanism regulating TDP-43 homeostasis. Here, we show that the uptake of oligodeoxynucleotides (ODNs) from the extracellular space induces reversible TDP-43 cytoplasmic puncta formation in both neurons and glia. ODNs facilitate the liquid-liquid phase separation of TDP-43 in vitro. Importantly, persistent accumulation of DNA in the cytoplasm leads to nuclear depletion of TDP-43 and enhanced production of a short isoform of TDP-43 (sTDP-43). In addition, in response to ODN uptake, the nuclear import receptor karyopherin subunit β1 (KPNB1) is sequestered in the cytosolic TDP-43 puncta. ALS-linked Q331K mutation decreases the dynamics of cytoplasmic TDP-43 puncta and increases the levels of sTDP-43. Moreover, the TDP-43 cytoplasmic puncta are induced by DNA damage and by impaired nuclear envelope integrity due to Lamin A/C deficiency. In summary, our data support that abnormal DNA accumulation in the cytoplasm may be one of the key mechanisms leading to TDP-43 proteinopathy and provides novel insights into molecular mechanisms of ALS caused by TDP-43 mutations.}, } @article {pmid39550606, year = {2024}, author = {Rabadi, MH and Russell, KA and Xu, C}, title = {Analysis of Mortality Causes and Locations in Veterans with ALS: A Decade Review.}, journal = {Medical science monitor : international medical journal of experimental and clinical research}, volume = {30}, number = {}, pages = {e945816}, pmid = {39550606}, issn = {1643-3750}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/mortality/physiopathology ; *Veterans ; Male ; Female ; Middle Aged ; Aged ; *Cause of Death ; Retrospective Studies ; United States/epidemiology ; Adult ; Aged, 80 and over ; }, abstract = {BACKGROUND Amyotrophic lateral sclerosis (ALS) is a motor neuron disease that leads to rapid degeneration of nerves in the brain and spinal cord, with eventual loss of voluntary movements, including breathing. This retrospective study of medical record data from 105 US veterans diagnosed with ALS at the Oklahoma City VA Medical Center between 2010 and 2021 aimed to identify patient demographics, and the causes and places of death for these veterans. MATERIAL AND METHODS Data from 105 US veterans diagnosed with ALS by the El Escorial criteria and supported by neurophysiology testing was reviewed. The information about the place and cause of death was obtained from each patient's care provider and death certificate. Crude mortality rates (per 100 person-years) and standardized mortality ratios (SMRs) were calculated for the causes of death, by sex, age group, and location of death. RESULTS During the 11-year follow-up period, 80 (76.2%) veterans with ALS died. The mean (SD) follow-up time was 4.53 (4.55) years. Most of the deaths were due to respiratory failure and pneumonia (n=43, mortality rate=9.21 per 100 person-years). Most patients died at home (n=71, 88.7%). The annual crude mortality rate was 16.7 and the all-cause death SMR was 25.63 (95% CI, 20.32-31.55). CONCLUSIONS This study's findings are that in veterans with ALS, the main cause of death is respiratory disease (failure). The main location of death was the home, with their family members. The all-cause mortality rate among veterans with ALS was 26 times greater than for the general Oklahoma population.}, } @article {pmid39550435, year = {2024}, author = {Wang, Z and Cao, W and Deng, B and Fan, D}, title = {Lower creatinine-to-cystatin c ratio associated with increased risk of incident amyotrophic lateral sclerosis in the prospective UK biobank cohort.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {28289}, pmid = {39550435}, issn = {2045-2322}, support = {81873784//National Natural Science Foundation of China/ ; BYSYDL2019002//Peking University Third Hospital/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/blood/epidemiology ; Humans ; Male ; Female ; *Creatinine/blood ; Middle Aged ; United Kingdom/epidemiology ; Aged ; Incidence ; Prospective Studies ; *Cystatin C/blood ; Risk Factors ; *Biological Specimen Banks ; *Biomarkers/blood ; Proportional Hazards Models ; Adult ; UK Biobank ; }, abstract = {Reduced muscle mass has been associated with the progression and prognosis of amyotrophic lateral sclerosis (ALS). However, it remains unclear whether decreased muscle mass is a risk factor for ALS or a consequence of motor neuron degeneration. Recently, serum creatinine-to-cystatin C ratio (CCR) have emerged as promising biomarkers for assessing muscle mass. We aimed to explore the association between CCR and the incidence of ALS using data from the UK Biobank. Between 2006 and 2010, 446,945 participants were included in the baseline. CCR was calculated as the ratio of serum creatinine to cystatin C. Cox regression models were used to analyze the relationship between CCR and ALS incidence. Furthermore, subgroup analyses were conducted to investigate potential covariates in these relationships. After adjusting for all covariates, the multivariate Cox regression analysis revealed a significant association between decreased CCR and an increased risk of ALS (hazard ratio (HR) = 0.990, 95% confidence interval (CI): 0.982-0.999, P = 0.026). Participants were stratified into groups based on CCR tertiles. Compared with participants in the highest tertiles of CCR, those in the lowest (HR = 1.388, 95% CI: 1.032-1.866, P = 0.030) and medium tertiles (HR = 1.348, 95% CI: 1.045-1.739, P = 0.021) had an increased risk of ALS incidence. Subgroup analysis showed that the relationship between CCR and ALS incidence was particularly significant among participants aged < 65 years (CCR tertile 1: HR = 1.916, 95% CI: 1.366-2.688, P < 0.001; CCR tertile 2: HR = 1.699, 95% CI: 1.267-2.278, P < 0.001). The present results demonstrate that lower CCR is significantly associated with a higher risk of ALS.}, } @article {pmid39548852, year = {2025}, author = {Dellar, ER and Vendrell, I and Amein, B and Lester, DG and Edmond, EC and Yoganathan, K and Dharmadasa, T and Sogorb-Esteve, A and Fischer, R and Talbot, K and Rohrer, JD and Turner, MR and Thompson, AG}, title = {Elevated Cerebrospinal Fluid Ubiquitin Carboxyl-Terminal Hydrolase Isozyme L1 in Asymptomatic C9orf72 Hexanucleotide Repeat Expansion Carriers.}, journal = {Annals of neurology}, volume = {97}, number = {3}, pages = {449-459}, pmid = {39548852}, issn = {1531-8249}, support = {2018-I2M-2-002//Chinese Academy of Medical Sciences Innovation Fund for Medical Science/ ; Lester/2450/795/MNDA_/Motor Neurone Disease Association/United Kingdom ; Thompson/Jan20/952-795/MNDA_/Motor Neurone Disease Association/United Kingdom ; MR/T006927/1/MRC_/Medical Research Council/United Kingdom ; MR/Y001095/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Humans ; *C9orf72 Protein/genetics ; Male ; Female ; Middle Aged ; Cross-Sectional Studies ; *Amyotrophic Lateral Sclerosis/genetics/cerebrospinal fluid ; Aged ; *Frontotemporal Dementia/genetics/cerebrospinal fluid ; DNA Repeat Expansion/genetics ; Adult ; Heterozygote ; Biomarkers/cerebrospinal fluid ; Neurofilament Proteins/cerebrospinal fluid ; }, abstract = {OBJECTIVE: To identify biochemical changes in individuals at higher risk of developing amyotrophic lateral sclerosis (ALS) or frontotemporal dementia (FTD) via C9orf72 hexanucleotide repeat expansion (HRE) heterozygosity.

METHODS: Cross-sectional observational study of 48 asymptomatic C9orf72 HRE carriers, 39 asymptomatic non-carrier controls, 19 people with sporadic ALS, 10 with C9orf72 ALS, 14 with sporadic FTD, and 10 with C9orf72 FTD. Relative abundance of 30 pre-defined cerebrospinal fluid biomarkers of ALS and FTD were compared in asymptomatic C9orf72 HRE carriers and age-matched non-carrier controls. Differential abundance of these proteins was quantified using data independent acquisition mass spectrometry or electro chemiluminescent assay for neurofilament light chain. Unbiased analysis of the entire cerebrospinal fluid proteome was then carried out.

RESULTS: Ubiquitin carboxyl-hydrolase isozyme L1 levels were higher in asymptomatic C9orf72 HRE carriers compared with age-matched non-carriers (log2fold change 0.20, FDR-adjusted p-value = 0.034), whereas neurofilament light chain levels did not significantly differ. Ubiquitin carboxyl-hydrolase isozyme L1 levels remained elevated after matching of groups by neurofilament levels (p = 0.011), and after adjusting for age, sex, and neurofilament levels. A significant difference was also observed when restricting analysis to younger participants (<37) matched by neurofilament level (p = 0.007).

INTERPRETATION: Elevated cerebrospinal fluid ubiquitin carboxyl-hydrolase isozyme L1 levels in C9orf72 HRE carriers can occur in the absence of increased neurofilament levels, potentially reflecting either compensatory or pathogenic mechanisms preceding rapid neuronal loss. This brings forward the window on changes associated with the C9orf72 HRE carrier state, with potential to inform understanding of penetrance and approaches to prevention. ANN NEUROL 2025;97:449-459.}, } @article {pmid39548731, year = {2024}, author = {Shino, Y and Muraki, N and Kobatake, Y and Kamishina, H and Kato, R and Furukawa, Y}, title = {Disulfide-mediated oligomerization of mutant Cu/Zn-superoxide dismutase associated with canine degenerative myelopathy.}, journal = {Protein science : a publication of the Protein Society}, volume = {33}, number = {12}, pages = {e5210}, pmid = {39548731}, issn = {1469-896X}, support = {JP21am0101083//Japan Agency for Medical Research and Development/ ; 19H05765//The Ministry of Education, Culture, Sports, Science and Technology (MEXT)/ ; 22H02768//The Ministry of Education, Culture, Sports, Science and Technology (MEXT)/ ; 22K19389//The Ministry of Education, Culture, Sports, Science and Technology (MEXT)/ ; 23EXC334//Exploratory Research Center on Life and Living Systems, National Institutes of Natural Sciences/ ; }, mesh = {Animals ; Dogs ; *Disulfides/chemistry/metabolism ; *Superoxide Dismutase-1/genetics/chemistry/metabolism ; Protein Multimerization ; Dog Diseases/genetics ; Spinal Cord Diseases/genetics/metabolism ; Amino Acid Substitution ; Zinc/metabolism/chemistry ; Mutation ; Mutation, Missense ; Copper/metabolism/chemistry ; }, abstract = {A homozygous E40K mutation in the gene coding canine Cu/Zn-superoxide dismutase (cSOD1) causes degenerative myelopathy (DM) in dogs. A pathological hallmark of DM with the cSOD1 mutation is the aggregation of mutant cSOD1 proteins in neurons. The amino acid substitution E40K disrupts a salt bridge between Glu40 and Lys91 and is considered to destabilize the native state of cSOD1; however, the mechanism by which mutant cSOD1 aggregates remains unclear. Here, we show that mutant cSOD1 losing a copper and zinc ion forms oligomers crosslinked via disulfide bonds. The E40K substitution was found to result in the increased solvent exposure of the Cys7 side chain, which then attacked the disulfide bond (Cys57-Cys146) in cSOD1 to form disulfide-linked oligomers. We also successfully prevented the Cys7 exposure and thus the oligomerization of mutant cSOD1 by a fragment antibody that specifically recognizes the region around the mutation site. The fragment antibody covered the β-plug region, reinforcing the interactions compromised by the E40K substitution and thus contributing to the maintenance of the structural integrity of the β-barrel core of cSOD1. Taken together, we propose that the Cys7 exposure in cSOD1 upon the salt bridge disruption plays a central role in the aggregation mechanism of DM-associated mutant cSOD1.}, } @article {pmid39548508, year = {2024}, author = {Panei, FP and Di Rienzo, L and Zacco, E and Armaos, A and Tartaglia, GG and Ruocco, G and Milanetti, E}, title = {Synchronized motion of interface residues for evaluating protein-RNA complex binding affinity: Application to aptamer-mediated inhibition of TDP-43 aggregates.}, journal = {Protein science : a publication of the Protein Society}, volume = {33}, number = {12}, pages = {e5201}, pmid = {39548508}, issn = {1469-896X}, support = {855923//ERC-2019-Synergy Grant (ASTRA, 855923)/ ; ivBM4PAP,101098989//EIC-2022-PathfinderOpen/ ; CN00000041//National Center for Gene Therapy and Drugs Based on RNA Technology/ ; CUPj33C22001130001//Potenziamento Strutture di Ricerca e Creazione di Campioni Nazionali Di R&S/ ; }, mesh = {*Aptamers, Nucleotide/chemistry/metabolism ; *Molecular Dynamics Simulation ; Humans ; *DNA-Binding Proteins/chemistry/metabolism ; *Protein Binding ; RNA/chemistry/metabolism ; Molecular Docking Simulation ; }, abstract = {Investigating the binding between proteins and aptamers, such as peptides or RNA molecules, is of crucial importance both for understanding the molecular mechanisms that regulate cellular activities and for therapeutic applications in several pathologies. Here, a new computational procedure, employing mainly docking, clustering analysis, and molecular dynamics simulations, was designed to estimate the binding affinities between a protein and some RNA aptamers, through the investigation of the dynamical behavior of the predicted molecular complex. Using the state-of-the-art software catRAPID, we computationally designed a set of RNA aptamers interacting with the TAR DNA-binding protein 43 (TDP-43), a protein associated with several neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). We thus devised a computational protocol to predict the RNA-protein molecular complex, so that the structural and dynamical behavior of such a complex can be investigated through extensive molecular dynamics simulation. We hypothesized that the coordinated and synchronized motion of the protein-binding residues, when in contact with RNA molecule, is a critical requisite in order to have a stable binding. Indeed, we calculated the motion covariance exhibited by the interface residues during molecular dynamics simulation: we tested the results against experimental measurements of binding affinity (in this case, the dissociation constant) for six RNA molecules, resulting in a linear correlation of about 0.9. Our findings suggest that the synchronized movement of interface residues plays a pivotal role in ensuring the stability within RNA-protein complexes, moreover providing insights into the contribution of each interface residue. This promising pipeline could thus contribute to the design of RNA aptamers interacting with proteins.}, } @article {pmid39548409, year = {2024}, author = {Ruan, K and Cheng, D and Zhu, X and Sun, S and Bao, F and Zhu, J and Li, F and Shen, M and Ye, Y}, title = {Corneal higher-order aberrations and their relationship with choroid in myopic patients.}, journal = {BMC ophthalmology}, volume = {24}, number = {1}, pages = {500}, pmid = {39548409}, issn = {1471-2415}, support = {81900910//Innovative Research Group Project of the National Natural Science Foundation of China/ ; LQ19H120003//Natural Science Foundation of Zhejiang Province/ ; Y2023809, Y20190638//Basic Scientific Research Project of Wenzhou/ ; }, mesh = {Humans ; Female ; Male ; *Choroid/pathology/diagnostic imaging/blood supply ; Adult ; *Myopia/physiopathology/complications ; *Corneal Wavefront Aberration/physiopathology ; *Tomography, Optical Coherence/methods ; Young Adult ; *Cornea/pathology/diagnostic imaging ; Axial Length, Eye/pathology/diagnostic imaging ; Refraction, Ocular/physiology ; Visual Acuity/physiology ; Corneal Topography ; Middle Aged ; Cross-Sectional Studies ; }, abstract = {BACKGROUND: To investigate corneal higher-order aberrations (HOAs) and choroidal characteristics in myopic individuals and explore the association between HOAs and choroidal parameters.

METHODS: Myopic participants were categorized into three groups based on axial lengths (ALs). We compared corneal HOAs, including spherical (Z4[0]), comatic (Z3 [- 1] and Z3[1]), and trefoil (Z3 [- 3] and Z3[3]) aberrations, as well as choroidal vascularity index (CVI) and choroidal thickness (CT). Linear regression analysis was used to assess the relationships among corneal HOAs, CVI, CT, spherical equivalent, and AL.

RESULTS: Groups 1, 2, and 3 included 105, 98, and 118 eyes, respectively. Group 3 exhibited lower spherical HOA root mean square and Z4[0] values than group 1(p < 0.05). Group 1 showed lower Z3[1] levels than other groups (p < 0.001). Groups 1 and 2 had higher mean, central, and I2 vertical CVIs than group 3 (p < 0.05). Group 1 had a larger vertical S1 CVI than group 3 (p < 0.05). Group 3 had smaller horizontal CVI values in all regions except N2 (p < 0.05). Both the mean and CT in all regions decreased as AL increased (p < 0.001). The comatic (Z3[1]) and trefoil (Z3[3]) components were predictors of mean horizontal CVI, and the comatic (Z3[1]) component was correlated with both mean vertical and horizontal CT.

CONCLUSION: Longer AL myopic patients exhibited lower absolute values of spherical aberration and horizontal coma. Alterations in choroid in myopic patients correlated with corneal HOAs. Our results suggest a potential connection between the optical quality and ocular perfusion in myopia.}, } @article {pmid39548226, year = {2024}, author = {Qin, J and Wang, X and Fan, G and Zhang, W and Wu, X and Wang, B and Liu, Y}, title = {Identifying amyotrophic lateral sclerosis using diffusion tensor imaging, and correlation with neurofilament markers.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {28110}, pmid = {39548226}, issn = {2045-2322}, support = {202103021224405//the Basic Research Project of Shanxi Province/ ; 201903D321049//the Key Research and Development Project Plan of Shanxi Province concerning social advancement/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnostic imaging/cerebrospinal fluid/blood/pathology ; *Diffusion Tensor Imaging/methods ; Middle Aged ; Male ; Female ; *Neurofilament Proteins/cerebrospinal fluid/blood ; *Biomarkers/blood/cerebrospinal fluid ; Aged ; Adult ; ROC Curve ; Case-Control Studies ; Anisotropy ; Pyramidal Tracts/diagnostic imaging/pathology ; }, abstract = {To determine diagnostic value of diffusion tensor imaging (DTI) in amyotrophic lateral sclerosis (ALS) patients and investigate the association between DTI and neurofilaments (NFs), including serum and cerebrospinal fluid (CSF) levels of neurofilament light chain (NFL) and phosphorylated neurofilament heavy chain (pNFH). Forty-three clinically diagnosed ALS patients and 32 control subjects without neurological disorders underwent routine MRI (magnetic resonance imaging) and DTI scans. DTI parameters (mean diffusivity [MD] and fractional anisotropy [FA]) at axial levels of internal capsules and cerebral peduncles along the corticospinal tract (CST) were measured. The study compared the differences of DTI parameters between ALS patients and controls using the Mann-Whitney U test. Diagnostic efficacy of each DTI metric was evaluated using the receiver operating characteristic (ROC) curve. NFs (NFL and pNFH levels in serum and CSF) were measured by enzyme-linked immunosorbent assay. Correlation analyses were conducted between DTI parameters and NFs. Capsule-MD and Peduncle-MD in ALS patients were higher than those in controls; whereas Capsule-FA and Peduncle-FA in ALS patients were lower than those in controls (all, p < 0.05). The area under curve (AUC) was 0.730 for Capsule-FA, 0.828 for Capsule-MD, 0.890 for Peduncle-FA, and 0.896 for Peduncle-MD. Capsule-FA was negatively correlated with CSF-NFL (r = - 0.813, p < 0.001), Serum-NFL (r = - 0.493, p = 0.001), CSF-pNFH (r = - 0.637, p < 0.001), and Serum-pNFH (r = - 0.672, p < 0.001); Peduncle-FA negatively with CSF-NFL (r = - 0.562, p < 0.001), CSF-pNFH (r = - 0.506, p = 0.001), and Serum-pNFH (r = - 0.488, p = 0.001); Peduncle-MD positively with CSF-NFL (r = 0.516, p < 0.001), CSF-pNFH (r = 0.494, p = 0.001). DTI had superior performance in identifying ALS patients and could serve as a reliable predictor. DTI parameters related to neurofilament markers, and Capsule-FA may become a robust surrogate biomarker indicating disease severity and progression rate for ALS patients.}, } @article {pmid39547910, year = {2025}, author = {Khamaysa, M and El Mendili, M and Marchand, V and Querin, G and Pradat, PF}, title = {Quantitative spinal cord imaging: Early ALS diagnosis and monitoring of disease progression.}, journal = {Revue neurologique}, volume = {181}, number = {3}, pages = {172-183}, doi = {10.1016/j.neurol.2024.10.005}, pmid = {39547910}, issn = {0035-3787}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/diagnostic imaging/pathology ; Disease Progression ; *Spinal Cord/diagnostic imaging/pathology ; Early Diagnosis ; *Neuroimaging/methods ; Magnetic Resonance Imaging/methods ; Prognosis ; Biomarkers ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by the progressive degeneration of motor neurons in the cortex, brainstem, and spinal cord. This degeneration leads to muscular weakness, progressively impairing motor functions and ultimately resulting in respiratory failure. The clinical, genetic, and pathological heterogeneity of ALS, combined with the absence of reliable biomarkers, significantly challenge the efficacy of therapeutic trials. Despite these hurdles, neuroimaging, and particularly spinal cord imaging, has emerged as a promising tool. It provides insights into the involvement of both upper and lower motor neurons. Quantitative spinal imaging has the potential to facilitate early diagnosis, enable accurate monitoring of disease progression, and refine the design of clinical trials. In this review, we explore the utility of spinal cord imaging within the broader context of developing spinal imaging biomarkers in ALS. We focus on a both diagnostic and prognostic biomarker in ALS, highlighting its pivotal role in elucidating the disease's underlying pathology. We also discuss the existing limitations and future avenues for research, aiming to bridge the translational gap between academic research and its application in clinical practice and therapeutic trials.}, } @article {pmid39547816, year = {2024}, author = {Salmerón-Mendoza, AN and Aguilar-Vázquez, CA and Aguilar-Castillo, SJ}, title = {[Electromyography in atypical variants of motor neuron disease: a case series].}, journal = {Revista medica del Instituto Mexicano del Seguro Social}, volume = {62}, number = {4}, pages = {1-6}, doi = {10.5281/zenodo.11397347}, pmid = {39547816}, issn = {2448-5667}, mesh = {Humans ; Male ; Female ; Middle Aged ; *Electromyography ; Aged ; *Amyotrophic Lateral Sclerosis/diagnosis/physiopathology ; Adult ; Aged, 80 and over ; Motor Neuron Disease/diagnosis/physiopathology ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that affects both the upper and lower motor neurons, it has a heterogeneous clinical presentation, there are atypical variants that differ from the classic form of the disease. The criteria for diagnosis have evolved over time, with the support of electromyography (EMG), we present a patient series with these variants in which EMG was crucial to make the diagnosis.

CLINICAL CASES: Six cases are described with atypical presentation of motor neuron disease, for the isolated bulbar ALS phenotype, three cases are reported: two male patients (68 and 62 years old) and one woman (33 years old), with initial symptoms in the bulbar segment and late progression. to a second segment, corroborating characteristic findings by EMG. For the variant of Vulpian-Bernhardt syndrome (VBS), two male patients aged 82 and 72 years are reported, with initial symptoms in the thoracic segment with electromyographic support for the diagnosis; Finally, a case of amyotrophic diplegia of the legs (APD) is described in a 50-year-old female patient with symptoms isolated to the pelvic limbs, with a slow clinical evolution, corroborated by EMG with involvement of other spinal segments.

CONCLUSIONS: ALS a spectrum of motor neuron disease, a neurodegenerative disease of the CNS, without curative treatment and one with a fatal outcome, the diagnosis of ELA is complex and becomes more complex for atypical phenotypes, as observed in the presented cases EMG is an essential part of the approach and part of the diagnostic criteria.}, } @article {pmid39546178, year = {2025}, author = {Li, N and Zhang, Z and Shen, L and Song, G and Tian, J and Liu, Q and Ni, J}, title = {Selenium metabolism and selenoproteins function in brain and encephalopathy.}, journal = {Science China. Life sciences}, volume = {68}, number = {3}, pages = {628-656}, pmid = {39546178}, issn = {1869-1889}, mesh = {*Selenoproteins/metabolism ; Humans ; *Selenium/metabolism/deficiency ; *Brain/metabolism ; Animals ; *Brain Diseases/metabolism ; Neurodegenerative Diseases/metabolism ; }, abstract = {Selenium (Se) is an essential trace element of the utmost importance to human health. Its deficiency induces various disorders. Se species can be absorbed by organisms and metabolized to hydrogen selenide for the biosynthesis of selenoproteins, selenonucleic acids, or selenosugars. Se in mammals mainly acts as selenoproteins to exert their biological functions. The brain ranks highest in the specific hierarchy of organs to maintain the level of Se and the expression of selenoproteins under the circumstances of Se deficiency. Dyshomeostasis of Se and dysregulation of selenoproteins result in encephalopathy such as Alzheimer's disease, Parkinson's disease, depression, amyotrophic lateral sclerosis, and multiple sclerosis. This review provides a summary and discussion of Se metabolism, selenoprotein function, and their roles in modulating brain diseases based on the most currently published literature. It focuses on how Se is utilized and transported to the brain, how selenoproteins are biosynthesized and function physiologically in the brain, and how selenoproteins are involved in neurodegenerative diseases. At the end of this review, the perspectives and problems are outlined regarding Se and selenoproteins in the regulation of encephalopathy.}, } @article {pmid39545975, year = {2024}, author = {Eickhoff, C and Schöne-Seifert, B and Kettemann, D and Bormann, E and Grehl, T and Boentert, M and Koch, JC and Schmitt, C and Schrank, B and Schröter, C and Meyer, T}, title = {[End of life perspectives: a systematic survey of patients with amyotrophic lateral sclerosis].}, journal = {Der Nervenarzt}, volume = {95}, number = {12}, pages = {1131-1138}, pmid = {39545975}, issn = {1433-0407}, mesh = {*Amyotrophic Lateral Sclerosis/therapy/psychology ; Humans ; Male ; Female ; Middle Aged ; *Terminal Care/psychology ; Aged ; *Advance Directives/psychology ; Surveys and Questionnaires ; Germany ; Adult ; Aged, 80 and over ; Noninvasive Ventilation ; Palliative Care ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a disease that still has to be primarily treated symptomatically or palliatively. It is therefore all the more important, in addition to initiating treatment, such as percutaneous endoscopic gastrostomy (PEG), noninvasive ventilation therapy (NIVT) and invasive ventilation therapy via tracheotomy (IVT), to discuss the possible termination of these measures early on.

QUESTION: What is the importance of advance directives for those affected and where are possible deficits in therapy planning for the end of life?

MATERIAL AND METHOD: Between March 2017 and January 2019 patients with a clinically confirmed diagnosis of ALS at six treatment centers were asked to fill out a questionnaire. A total of 328 people returned the completed forms.

RESULTS: Of the participants 72% had already made an advance directive (AD), 25% planned to fill one out and only 3% refused to do so. In composing the AD most patients (90%) had support, although 56% lacked medical counselling and only 18% had drawn up the will together with the doctor and relatives, with the majority of the rest also wanting support from a doctor. A total of 37% of all patients wanted a contact person to talk about their illness but only 40% of them had such a contact person. Of the patients 22% stated that they had considered suicide and of these only 55% stated that they had no contact person for the psychological stress caused by the illness but 31% wished to have such a person.

DISCUSSION AND CONCLUSION: A coordinated care of ALS patients, which also takes the psychosocial aspects into account is urgently needed.}, } @article {pmid39545606, year = {2024}, author = {A Virata, MC and Catahay, JA and Lippi, G and Henry, BM}, title = {Neurofilament light chain: a biomarker at the crossroads of clarity and confusion for gene-directed therapies.}, journal = {Neurodegenerative disease management}, volume = {14}, number = {6}, pages = {227-239}, pmid = {39545606}, issn = {1758-2032}, mesh = {Humans ; *Biomarkers/blood ; *Genetic Therapy/methods ; *Neurodegenerative Diseases/diagnosis/drug therapy/genetics ; *Neurofilament Proteins/blood ; }, abstract = {Neurofilament light chain (NfL) is a promising biomarker for neurodegenerative diseases, measurable in both CSF and blood upon neuroaxonal damage. While CSF analysis was traditionally used, blood-based assays now offer a less invasive alternative. NfL levels correlate with disease severity and progression in conditions like Alzheimer's disease, amyotrophic lateral sclerosis, multiple sclerosis and Huntington's disease. Clinical trials demonstrate its utility as a pharmacodynamic biomarker in MS and ALS. The FDA's approval of Tofersen for SOD1-ALS based on NfL reduction underscores its growing acceptance as surrogate marker. However, challenges remain in standardizing assays, interpreting clinical correlations, low specificity and understanding the dynamics between CSF and blood NfL levels. Addressing these issues is crucial for maximizing NfL's potential in neurodegenerative disease management.}, } @article {pmid39545045, year = {2024}, author = {Xu, X and Huang, Y and Zhu, Y and Jin, Q}, title = {Association between dietary patterns and the prognosis of amyotrophic lateral sclerosis in China: a cross-sectional study.}, journal = {Frontiers in nutrition}, volume = {11}, number = {}, pages = {1437521}, pmid = {39545045}, issn = {2296-861X}, abstract = {BACKGROUND: Recently, a growing number of studies have specifically examined the impact of dietary variables on the development and progression of amyotrophic lateral sclerosis (ALS). The purpose of this study was to investigate the correlation between different dietary patterns and Chinese ALS patients' prognosis.

METHODS: A retrospective study was conducted by recruiting 590 patients with ALS who attended and were regularly followed at hospitals in Nanjing from 2016 to 2023. Nutrient intake was calculated using dietary information collected through the food frequency questionnaire (FFQ), and patients were divided into a control group and special diet groups, including a high-calorie group (HC), a high-protein group (HP), and a ketogenic diet group (KD), based on their specific intake. And used the Kaplan-Meier product limiting distribution to compare the time required to transition between phases of different dietary patterns and to estimate cumulative survival probabilities.

RESULTS: Patients in the HP had a better nutritional status. And the disease progression rate (ΔFS) was significantly associated with dietary patterns, with the KD group having the lowest ΔFS. Meanwhile, special diets extended the survival time of stage 4 patients but had no effect on the overall survival of the disease.

CONCLUSION: A special diet can be one of effective options for patients with advanced ALS. Patients with poor nutritional status may choose the HP diet, whereas those with underlying conditions should consider the ketogenic diet with caution.}, } @article {pmid39544780, year = {2024}, author = {Silva, JF and de Souza, WM and Mello, JDC and Ceccato, HD and Oliveira, PSP and Ayrizono, MLS and Leal, RF}, title = {Evidence linking gut-brain axis and Crohn's disease, focusing on neurotrophic dysfunctions and radiological imaging analysis - a systematic review.}, journal = {American journal of translational research}, volume = {16}, number = {10}, pages = {6029-6040}, pmid = {39544780}, issn = {1943-8141}, abstract = {OBJECTIVE: To conduct a systematic review (SR) to find evidence for a connection between Crohn's disease (CD) and the gut-brain axis (GBA).

METHODS: This study conducted a systematic review (SR) employing a search strategy and strict inclusion criteria. It was conducted by searching for studies published between 2017 and 2024 in the following databases: PUBMED, PUBMED PMC, BVS-BIREME, SCOPUS, WEB OF SCIENCE, EMBASE, and COCHRANE.

RESULTS: Fifty original research articles were included. Among these, 20 studies addressed neuroimaging methods to evaluate CD patients' functional or structural brain changes. Neurodegenerative diseases were the second most addressed topic in the studies, with 18 articles related to different diseases such as Parkinson's disease, Alzheimer's disease, dementia, Amyotrophic Lateral Sclerosis, Multiple Sclerosis, and Multiple System Atrophy. Eight articles addressed sleep disorders related to CD; two explored Electroencephalography changes; one investigated Brain-Derived Neurotrophic Factor serum levels and one correlated vagotomy with CD.

CONCLUSION: Interest in the link between CD and GBA is increasing, but studies remain varied and inconclusive, spanning from epidemiology to brain imaging and neglecting to investigate a mechanistic relationship. This SR underscores the need for further research to better understand the potential role of GBA in the prognosis and etiology of CD, highlighting its complexity.}, } @article {pmid39544700, year = {2024}, author = {Parnianpour, P and Steinbach, R and Buchholz, IJ and Grosskreutz, J and Kalra, S}, title = {T1-weighted MRI texture analysis in amyotrophic lateral sclerosis patients stratified by the D50 progression model.}, journal = {Brain communications}, volume = {6}, number = {6}, pages = {fcae389}, pmid = {39544700}, issn = {2632-1297}, abstract = {Amyotrophic lateral sclerosis, a progressive neurodegenerative disease, presents challenges in predicting individual disease trajectories due to its heterogeneous nature. This study explores the application of texture analysis on T1-weighted MRI in patients with amyotrophic lateral sclerosis, stratified by the D50 disease progression model. The D50 model, which offers a more nuanced representation of disease progression than traditional linear metrics, calculates the sigmoidal curve of functional decline and provides independent quantifications of disease aggressiveness and accumulation. In this research, a representative cohort of 116 patients with amyotrophic lateral sclerosis was studied using the D50 model and texture analysis on MRI images. Texture analysis, a technique used for quantifying voxel intensity patterns in MRI images, was employed to discern alterations in brain tissue associated with amyotrophic lateral sclerosis. This study examined alterations of the texture feature autocorrelation across sub-groups of patients based on disease accumulation, aggressiveness and the first site of onset, as well as in direct regressions with accumulation/aggressiveness. The findings revealed distinct patterns of the texture-derived autocorrelation in grey and white matter, increase in bilateral corticospinal tract, right hippocampus and left temporal pole as well as widespread decrease within motor and extra-motor brain regions, of patients stratified based on their disease accumulation. Autocorrelation alterations in grey and white matter, in clusters within the left cingulate gyrus white matter, brainstem, left cerebellar tonsil grey matter and right inferior fronto-occipital fasciculus, were also negatively associated with disease accumulation in regression analysis. Otherwise, disease aggressiveness correlated with only two small clusters, within the right superior temporal gyrus and right posterior division of the cingulate gyrus white matter. The findings suggest that texture analysis could serve as a potential biomarker for disease stage in amyotrophic lateral sclerosis, with potential for quick assessment based on using T1-weighted images.}, } @article {pmid39542176, year = {2024}, author = {Tian, Z and Zhang, Q and Wang, L and Li, M and Li, T and Wang, Y and Cao, Z and Jiang, X and Luo, P}, title = {Progress in the mechanisms of pain associated with neurodegenerative diseases.}, journal = {Ageing research reviews}, volume = {102}, number = {}, pages = {102579}, doi = {10.1016/j.arr.2024.102579}, pmid = {39542176}, issn = {1872-9649}, mesh = {Humans ; *Neurodegenerative Diseases/metabolism/physiopathology ; *Pain/physiopathology/metabolism/etiology ; Animals ; Neuroinflammatory Diseases ; }, abstract = {Neurodegenerative diseases (NDDs) represent a class of neurological disorders characterized by the progressive degeneration or loss of neurons, impacting millions of individuals globally. In addition to the typical manifestations, pain is a prevalent symptom associated with NDDs, seriously impacting the quality of life for patients. The pathogenesis of pain associated with NDDs is intricate and multifaceted. Currently, the clinical management of NDDs-related pain symptoms predominantly relies on conventional pharmacological agents or physical therapy. However, these approaches often fail to produce satisfactory outcomes. This article summarizes the underlying mechanisms of major NDDs-associated pain: Neuroinflammation, Brain and spinal cord dysfunctions, Mitochondrial dysfunction, Risk gene and pathological protein, as well as Receptor, channel, and neurotransmitter. While numerous studies have investigated the downstream pathological processes associated with these mechanisms, there remains a significant gap in identifying the key initiating factors. Specifically, there is insufficient evidence for the upstream elements that activate microglia and astrocytes in neuroinflammation leading to pain in NDDs. Likewise, there is an absence of upstream factors elucidating how dysfunctions in the brain and spinal cord, as well as mitochondrial impairments, contribute to the development of pain. Furthermore, the specific mechanisms through which hallmark pathological proteins related to NDDs contribute to these pathological processes remain inadequately understood. The objective of this article is to synthesize the existing mechanisms underlying pain associated with NDDs, including Alzheimer's disease, Parkinson's disease, Huntington's disease, Schizophrenia, Amyotrophic lateral sclerosis, and Multiple sclerosis, while also identifying gaps and deficiencies in these mechanisms. This paper offers insights for future research trajectories. Given the intricate pathogenesis of NDDs-related pain, it emphasizes that a promising short-term strategy is combination therapy-intervening concurrently in multiple pathological processes-akin to the cocktail approach utilized in treating acquired immunodeficiency syndrome (AIDS). For long-term advancements, achieving breakthroughs in the treatment of the NDDs themselves will remain essential for alleviating accompanying pain symptoms.}, } @article {pmid39542047, year = {2024}, author = {Ghaderi, S and Fatehi, F and Kalra, S and Okhovat, AA and Nafissi, S and Mohammadi, S and Batouli, SAH}, title = {Metabolite alterations in the left dorsolateral prefrontal cortex and its association with cognitive assessments in amyotrophic lateral sclerosis: A longitudinal magnetic resonance spectroscopy study.}, journal = {Brain research bulletin}, volume = {219}, number = {}, pages = {111125}, doi = {10.1016/j.brainresbull.2024.111125}, pmid = {39542047}, issn = {1873-2747}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism/diagnostic imaging ; Male ; Female ; Middle Aged ; *Magnetic Resonance Spectroscopy/methods ; Longitudinal Studies ; Aged ; *Cognition/physiology ; *Dorsolateral Prefrontal Cortex/metabolism ; Choline/metabolism ; Creatine/metabolism ; Neuropsychological Tests ; Adult ; Cognitive Dysfunction/metabolism/diagnostic imaging ; Aspartic Acid/analogs & derivatives/metabolism ; Prefrontal Cortex/metabolism/diagnostic imaging ; }, abstract = {OBJECTIVE: To characterize the longitudinal metabolite profile of the left dorsolateral prefrontal cortex (DLPFC) in amyotrophic lateral sclerosis (ALS) using magnetic resonance spectroscopy (MRS) and to examine its correlation with cognitive assessments.

METHODS: Thirteen patients at baseline and ten at follow-up, along with 14 age-, sex-, and handedness-matched healthy controls (HCs), were recruited. Three Tesla with a 64-channel coil, Point-RESolved Spectroscopy (PRESS) sequence (TR=1500 ms and TE=140 ms) was used. Metabolites in the left DLPFC were quantified using LCModel. Cognitive performance and functional impairment were assessed using the Edinburgh Cognitive and Behavioral ALS Screen (ECAS) and Revised ALS Functional Rating Scale (ALSFRS-R), respectively. Group comparisons were adjusted for multiple comparisons (p < 0.05, Bonferroni correction). The links between the brain metabolites and cognitive function were investigated using relevant correlation tests (Pearson's or Spearman's).

RESULTS: Our analysis revealed a significant difference in the choline-to-creatine ratio (tCho/tCr) among the three groups. Baseline ALS patients showed a higher tCho/tCr ratio than HCs (p = 0.033, Bonferroni-corrected). Interestingly, the total N-acetyl aspartate (tNAA)/tCr ratio, a marker of neuronal health, was strongly positively correlated with visuospatial cognitive scores at baseline and follow-up. Furthermore, at follow-up, tNAA/tCr was positively correlated with the total scores and specific sub-scores on the ECAS, encompassing both ALS-specific and non-specific cognitive domains. At follow-up, positive correlations emerged between tNAA/tCr and the total language and executive function scores.

CONCLUSIONS: Metabolite alterations and correlations with cognition were observed in the left DLPFC of ALS patients, supporting extra-motor involvement and its association with cognitive decline.}, } @article {pmid39541975, year = {2025}, author = {Márquez-Moñino, MÁ and Santiveri, CM and de León, P and Camero, S and Campos-Olivas, R and Jiménez, MÁ and Sáiz, M and González, B and Pérez-Cañadillas, JM}, title = {The ALS drug riluzole binds to the C-terminal domain of SARS-CoV-2 nucleocapsid protein and has antiviral activity.}, journal = {Structure (London, England : 1993)}, volume = {33}, number = {1}, pages = {39-50.e6}, doi = {10.1016/j.str.2024.10.025}, pmid = {39541975}, issn = {1878-4186}, mesh = {*SARS-CoV-2/drug effects/metabolism ; *Antiviral Agents/pharmacology/chemistry ; Binding Sites ; Humans ; *Riluzole/pharmacology/chemistry/metabolism ; *Protein Binding ; Crystallography, X-Ray ; Coronavirus Nucleocapsid Proteins/chemistry/metabolism ; Phosphoproteins/metabolism/chemistry ; Protein Domains ; COVID-19 Drug Treatment ; Models, Molecular ; }, abstract = {Nucleoproteins (N) play an essential role in virus assembly and are less prone to mutation than other viral structural proteins, making them attractive targets for drug discovery. Using an NMR fragment-based drug discovery approach, we identified the 1,3-benzothiazol-2-amine (BZT) group as a scaffold to develop potential antivirals for SARS-CoV-2 nucleocapsid (N) protein. A thorough characterization of BZT derivatives using NMR, X-ray crystallography, antiviral activity assays, and intrinsic fluorescence measurements revealed their binding in the C-terminal domain (CTD) domain of the N protein, to residues Arg 259, Trp 330, and Lys 338, coinciding with the nucleotide binding site. Our most effective compound exhibits a slightly better affinity than GTP and the ALS drug riluzole, also identified during the screening, and displays notable viral inhibition activity. A virtual screening of 218 BZT-based compounds revealed a potential extended binding site that could be exploited for the future development of new SARS-CoV-2 antivirals.}, } @article {pmid39541203, year = {2024}, author = {Russo, A and Maiorano, G and Cortese, B and D'Amone, S and Invidia, A and Quattrini, A and Romano, A and Gigli, G and Palamà, IE}, title = {Optimizing TDP-43 silencing with siRNA-loaded polymeric nanovectors in neuronal cells for therapeutic applications: balancing knockdown and function.}, journal = {Nanoscale}, volume = {16}, number = {48}, pages = {22337-22349}, doi = {10.1039/d4nr03159h}, pmid = {39541203}, issn = {2040-3372}, mesh = {*DNA-Binding Proteins/metabolism/genetics/chemistry ; *RNA, Small Interfering/chemistry/metabolism ; Humans ; *Neurons/metabolism/pathology ; Amyotrophic Lateral Sclerosis/therapy/metabolism/pathology/genetics ; Polymers/chemistry ; Nanoparticles/chemistry ; Gene Knockdown Techniques ; Cell Line, Tumor ; Gene Silencing ; }, abstract = {TAR DNA-binding protein 43 (TDP-43) is a ubiquitously expressed DNA/RNA binding protein critical for regulating gene expression, including transcription, splicing, mRNA stability, and protein translation. Aggregation of pathological TDP-43 proteins in the cytoplasm of neurons and glial cells appears to be a common feature of amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases such as frontotemporal dementia (FTD), contributing to motor neuron degeneration and clinical symptoms. Downregulation of TDP-43 expression to prevent or reduce the formation of pathological aggregates is a potential therapeutic approach for treating TDP-43-related diseases. However, therapeutic strategies to reduce TDP-43 aggregation face significant challenges, as the downregulation of TDP-43 must balance the need to maintain its normal functions, which are essential for RNA metabolism and cellular homeostasis. In this study, we developed novel polymeric nanovectors for the delivery of TDP-43 siRNAs in neuronal cells. These nanovectors were designed to provide adequate TDP-43 silencing to achieve the desired functional reduction of TDP-43 levels, thereby optimizing its impact on cellular functions. Our results demonstrate that the polymeric nanovector formulations effectively reduced TDP-43 mRNA and protein levels to an extent comparable to those observed with traditional lipid-based systems. Concurrently, the polymeric nanovectors exhibited an enhanced capacity to reduce stress granules (SG) formation and facilitate TDP-43-containing SG disassembly, while preserving its essential cellular functions. This study provides the first evidence that polymeric nanovectors may be a valuable tool for developing therapeutic strategies to treat TDP-43 protein diseases, such as ALS and FTD, by directly silencing TDP-43 to reduce its aggregation.}, } @article {pmid39539269, year = {2024}, author = {Risen, S and Sharma, S and Gilberto, VS and Brindley, S and Aguilar, M and Brown, JM and Chatterjee, A and Moreno, JA and Nagpal, P}, title = {Large- and Small-Animal Studies of Safety, Pharmacokinetics, and Biodistribution of Inflammasome-Targeting Nanoligomer in the Brain and Other Target Organs.}, journal = {ACS pharmacology & translational science}, volume = {7}, number = {11}, pages = {3439-3451}, pmid = {39539269}, issn = {2575-9108}, abstract = {Immune malfunction or misrecognition of healthy cells and tissue, termed autoimmune disease, is implicated in more than 80 disease conditions and multiple other secondary pathologies. While pan-immunosuppressive therapies like steroids can offer limited relief for systemic inflammation for some organs, many patients never achieve remission, and such drugs do not cross the blood-brain barrier, making them ineffective for tackling neuroinflammation. Especially in the brain, unintended activation of microglia and astrocytes is hypothesized to be directly or indirectly responsible for multiple sclerosis, amyotrophic lateral sclerosis, Parkinson's disease, and Alzheimer's disease. Recent studies have also shown that targeting inflammasomes and specific immune targets can be beneficial for these diseases. Furthermore, our previous studies have shown targeting NF-κB and NLRP3 through brain penetrant Nanoligomer cocktail SB_NI_112 (abbreviated as NI112) can be therapeutic for several neurodegenerative diseases. Here, we show safety-toxicity studies, followed by pharmacokinetics and biodistribution in small- (mice) and large-animal (dog) studies of this inflammasome-targeting Nanoligomer cocktail NI112. We conducted studies using four different routes of administration: intravenous, subcutaneous, intraperitoneal, and intranasal, and identified the drug concentration over time using inductively coupled plasma mass spectrometry in the blood serum, the brain (including different brain regions), and other target organs such as liver, kidney, and colon. Our results indicate that the Nanoligomer cocktail has a strong safety profile and shows high biodistribution (F ∼ 0.98) and delivery across multiple routes of administration. Further analysis showed high brain bioavailability with a ratio of NI112 in brain tissue to blood serum of ∼30%. Our model accurately shows dose scaling, translation between different routes of administration, and interspecies scaling. These results provide an excellent platform for human clinical translation and prediction of therapeutic dosage between different routes of administration.}, } @article {pmid39538364, year = {2025}, author = {Terra, R and Éthier, V and Busque, L and Morin-Quintal, A and D'Angelo, G and Hébert, J and Wang, X and Lépine, G and LeBlanc, R and Bergeron, J}, title = {Improved identification of clinically relevant Acute Leukemia subtypes using standardized EuroFlow panels versus non-standardized approach.}, journal = {Cytometry. Part B, Clinical cytometry}, volume = {108}, number = {2}, pages = {116-127}, doi = {10.1002/cyto.b.22213}, pmid = {39538364}, issn = {1552-4957}, support = {//BD Biosciences/ ; }, mesh = {Humans ; *Flow Cytometry/methods/standards ; Immunophenotyping/methods ; *Leukemia, Myeloid, Acute/diagnosis/pathology/genetics ; Dendritic Cells/pathology ; Female ; Male ; Middle Aged ; *Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/diagnosis/pathology ; Adult ; Aged ; }, abstract = {Rare acute leukemia (AL) components or subtypes such as blastic plasmacytoid dendritic cell neoplasm (BPDCN) or early T-cell precursor acute Lymphoblastic Leukemia (ETP-ALL) can be difficult to detect by routine flow cytometry due to their immunophenotypes overlapping with other poorly differentiated AL. We hypothesized that using standardized EuroFlow™ Consortium approach could better diagnose such entities among cases that previously classified as acute myeloid leukemia (AML)-M0, AML with minimal differentiation, AML with myelodysplasia-related changes without further lineage differentiation, and AL of ambiguous lineage. In order to confirm this hypothesis and assess whether these AL subtypes such as BPDCN and ETP-ALL had previously gone undetected, we reanalyzed 49 banked cryopreserved sample cases using standardized EuroFlow™ Consortium panels. We also performed target sequencing to capture the mutational commonalities between these AL subtypes. Reanalysis led to revised or refined diagnoses for 23 cases (47%). Of these, five diagnoses were modified, uncovering 3 ETP-ALL and 2 typical BPDCN cases. In 12 AML cases, a variable proportion of immature plasmacytoid dendritic cell and/or monocytic component was newly identified. In one AML case, we have identified a megakaryoblastic differentiation. Finally, in five acute lymphoblastic leukemia (ALL) cases, we were able to more precisely determine the maturation stage. The application of standardized EuroFlow flow cytometry immunophenotyping improves the diagnostic accuracy of ALs and could impact treatment decisions.}, } @article {pmid39538124, year = {2024}, author = {Sun, Y and Hu, S and Lan, Y and Wang, R and Wei, S and Huang, H and Cui, H and Li, X and Huang, Z}, title = {Investigation of resistance mechanisms to flucarbazone-sodium in wild oat (Avena fatua L.) from China.}, journal = {BMC plant biology}, volume = {24}, number = {1}, pages = {1073}, pmid = {39538124}, issn = {1471-2229}, mesh = {*Avena/genetics/drug effects ; China ; Herbicide Resistance/genetics ; Herbicides/pharmacology ; Plant Proteins/genetics/metabolism ; Gene Expression Regulation, Plant/drug effects ; Plant Weeds/genetics/drug effects ; }, abstract = {BACKGROUND: Wild oat (Avena fatua L.) is a self-pollinating, allohexaploid species in the family Gramineae (grasses), which is a malignant weed that mainly harms crops such as wheat. In recent years, a decline in the control efficiency of flucarbazone-sodium against wild oat has occurred in some regions of China.

RESULTS: We identified an ALS-resistant A. fatua population (R population). Whole-plant response assays revealed that the R population exhibited a moderate level of resistance (5.9-fold) to flucarbazone-sodium. Pre-treatment with malathion significantly reduced flucarbazone-sodium resistance in the R population. The known mutation sites and ALS gene relative expression that confer resistance to ALS inhibitor herbicides were not found in R population. Following flucarbazone-sodium treatment, the expression of eight genes related to metabolic enzymes was investigated using quantitative real-time PCR (qRT-PCR). CYP92A6 and the Aldo/keto reductase family were highly expressed in the R population after the application of flucarbazone-sodium.

CONCLUSIONS: The mechanism of flucarbazone-sodium resistance in A. fatua is mediated by NTSR, nor TSR. Two genes, CYP92A6 and the Aldo/keto reductase family, were discovered to be possibly related in the metabolism of NTSR in the A. fatua population, justifying more functional studies. The results will serve as a data resource for further studies on the molecular mechanisms of A. fatua to flucarbazone-sodium.}, } @article {pmid39537536, year = {2025}, author = {Zou, J and Meng, X and Hong, Z and Rao, Y and Wang, K and Li, J and Yu, H and Wang, C}, title = {Cas9-PE: a robust multiplex gene editing tool for simultaneous precise editing and site-specific random mutation in rice.}, journal = {Trends in biotechnology}, volume = {43}, number = {2}, pages = {433-446}, doi = {10.1016/j.tibtech.2024.10.012}, pmid = {39537536}, issn = {1879-3096}, mesh = {*CRISPR-Associated Protein 9/genetics/metabolism ; *Gene Editing/instrumentation/methods ; *Oryza/genetics ; Mutation ; *Mutagenesis, Site-Directed ; Acetolactate Synthase/genetics ; Herbicide Resistance/genetics ; }, abstract = {In molecular design breeding, the simultaneous introduction of desired functional genes through specific nucleotide modifications and the elimination of genes regulating undesired phenotypic traits or agronomic components require advanced gene editing tools. Due to limited editing efficiency, even with the use of highly precise editing tools, such as prime editing (PE), simultaneous editing of multiple mutation types poses a challenge. Here, we replaced Cas9 nickase (nCas9) with Cas9 to construct a Cas9-mediated PE (Cas9-PE) system in rice. This system not only enables precise editing, but also allows for site-specific random mutation. Moreover, leveraging the precision of Cas9-PE, we established a transgene-free multiplex gene editing system using a co-editing strategy. This strategy involved the Agrobacterium-mediated transient expression of the precise editing rice endogenous acetolactate synthase gene ALS[S627I] to confer herbicide bispyribac-sodium (BS) resistance as a selection marker. This study provides a versatile and efficient multiplex gene editing tool for molecular design breeding.}, } @article {pmid39536963, year = {2025}, author = {Casiraghi, V and Sorce, MN and Santangelo, S and Invernizzi, S and Bossolasco, P and Lattuada, C and Battaglia, C and Venturin, M and Silani, V and Colombrita, C and Ratti, A}, title = {Modeling of TDP-43 proteinopathy by chronic oxidative stress identifies rapamycin as beneficial in ALS patient-derived 2D and 3D iPSC models.}, journal = {Experimental neurology}, volume = {383}, number = {}, pages = {115057}, doi = {10.1016/j.expneurol.2024.115057}, pmid = {39536963}, issn = {1090-2430}, mesh = {Humans ; *Induced Pluripotent Stem Cells/drug effects ; *Amyotrophic Lateral Sclerosis/pathology/metabolism/drug therapy ; *Oxidative Stress/drug effects/physiology ; *Sirolimus/pharmacology ; *TDP-43 Proteinopathies/pathology/metabolism ; DNA-Binding Proteins/metabolism/genetics ; Arsenites/toxicity/pharmacology ; Sodium Compounds/toxicity/pharmacology ; Motor Neurons/drug effects/metabolism/pathology ; }, abstract = {Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disorder characterized neuropathologically by TDP-43 proteinopathy with loss of TDP-43 nuclear splicing activity and formation of cytoplasmic TDP-43 aggregates. The lack of suitable experimental models of TDP-43 proteinopathy has hampered the discovery of effective therapies. We already showed that chronic and mild oxidative insult by sodium arsenite (ARS) triggered TDP-43 cytoplasmic aggregation and stress granules (SGs) formation in ALS patient-derived fibroblasts and motor neurons differentiated from induced pluripotent stem cells (iPSC-MNs). However, whether this insult induces a reduction of TDP-43 splicing activity in the nucleus, thus recapitulating both gain and loss of function pathomechanisms, still remains to be determined. In this study we first showed that chronic ARS in human neuroblastoma cells triggered TDP-43 cytoplasmic mislocalization, SGs formation and defective splicing of TDP-43 target genes UNC13A and POLDIP3 as functional readouts of TDP-43 proteinopathy. Additionally, a dysregulation of autophagy and senescence markers was observed in this condition. In a preliminary drug screening approach with autophagy-promoting drugs, namely rapamycin, lithium carbonate and metformin, only rapamycin prevented ARS-induced loss of TDP-43 splicing activity. We then demonstrated that, in addition to TDP-43 cytoplasmic aggregation, chronic ARS triggered TDP-43 loss of splicing activity also in ALS patient-derived primary fibroblasts and iPSC-MNs and that rapamycin was beneficial to reduce these TDP-43 pathological features. By switching to a neuro-glial 3D in vitro model, we observed that treatment of ALS iPSC-brain organoids with chronic ARS also induced a defective TDP-43 splicing activity which was prevented by rapamycin. Collectively, we established different human cell models of TDP-43 proteinopathy which recapitulate TDP-43 gain and loss of function, prevented by rapamycin administration. Human neuroblastoma cells and patient-derived fibroblasts and 2D- and 3D-iPSC models exposed to chronic oxidative stress represent therefore suitable in vitro platforms for future drug screening approaches in ALS.}, } @article {pmid39536438, year = {2024}, author = {Henderson, NL and Ortiz-Olguin, E and Bourne, G and Pywell, C and Rose, JB and Williams, GR and Nipp, RD and Rocque, GB}, title = {Implementation of ePROs Into Multidisciplinary Tumor Board Discussions for Patients With Pancreatic Cancer: The INSPIRE Intervention.}, journal = {Journal of the National Comprehensive Cancer Network : JNCCN}, volume = {22}, number = {9}, pages = {602-609}, doi = {10.6004/jnccn.2024.7052}, pmid = {39536438}, issn = {1540-1413}, mesh = {Humans ; *Pancreatic Neoplasms/therapy ; Female ; Male ; *Patient Reported Outcome Measures ; Aged ; Middle Aged ; Patient Care Team/standards ; Surveys and Questionnaires ; }, abstract = {BACKGROUND: The incorporation of electronic patient-reported outcomes (ePROs), such as the Geriatric Assessment (GA) and treatment preferences, into decision-making for pancreatic cancer has been limited by clinician- and system-level barriers concerning workflow. We hypothesized that ePRO inclusion within multidisciplinary tumor boards (MDTBs) would circumvent barriers and provide a venue for systematic consideration of critical patient-provided information.

PATIENTS AND METHODS: The INtegrating Systematic PatIent-Reported Evaluations (INSPIRE) intervention consists of (1) patient survey completion, including GA and patient preferences, and (2) screensharing patient ePROs during MDTBs. Proctor et al's implementation outcomes were assessed, with penetration (the proportion of consented patients who were presented at MDTBs) acting as the primary outcome (considered successful at 70%). Secondary outcomes included adoption, feasibility, acceptability, appropriateness, cost, and sustainability, assessed by clinician post-MDTB exit surveys, clinician postintervention surveys, clinician postintervention semistructured interviews, and time-coding analysis of recorded and transcribed historical (November 2021-February 2022) and intervention (September 2022-June 2023) MDTBs.

RESULTS: A total of 50 patients completed surveys and all were presented at MDTBs (penetration=100%). All eligible clinicians (n=9) enrolled patients (adoption=100%) and reported that ePROs were useful in 90% and led to a change in treatment plan in 30% of cases. In postintervention surveys and interviews, clinicians primarily responded positively to feasibility, acceptability, and appropriateness questions. Time-coding analysis found a modest time cost of an additional 51.1 seconds in mean discussion time-per-patient between preintervention (mean [SD], 172.7 [111.4] seconds) and intervention patients (mean [SD], 223.8 [107.1] seconds); 86% of clinicians reported the intervention did not take too much time. All surveyed clinicians reported interest in continuing the intervention and suggested adaptations to further promote sustainability.

CONCLUSIONS: The integration of ePROs into pancreatic MDTBs was feasible and acceptable, providing a potential approach to increase the utilization of ePROs by clinical teams in their management of patients with pancreatic cancer.}, } @article {pmid39535960, year = {2025}, author = {Soares, RV and Pedrosa, RBDS and Sandars, J and Cecilio-Fernandes, D}, title = {The importance of combined use of spacing and testing effects for complex skills training: A quasi-experimental study.}, journal = {Medical teacher}, volume = {47}, number = {8}, pages = {1296-1303}, doi = {10.1080/0142159X.2024.2427735}, pmid = {39535960}, issn = {1466-187X}, mesh = {Humans ; *Clinical Competence ; Female ; Male ; *Educational Measurement/methods ; Students, Nursing/psychology ; Retention, Psychology ; *Simulation Training/methods ; Adult ; Young Adult ; }, abstract = {INTRODUCTION: A major challenge is retention of complex clinical skills. Spacing training and testing have been demonstrated to increase knowledge and skill retention but the combination has not been previously investigated in complex clinical skills. The aim of our study was to compare the effectiveness of combined spacing and testing for Basic Life Support (BLS) and Advance Life Support (ALS) simulation training in one group (intervention group), with combined spacing and testing, and another group (control) that received simulation training in a single-session simulation training without testing.

METHODS: A quasi-experimental study.

RESULTS: Thirteen nursing students were in the intervention group and 18 in the control group. After three months, there was no significant reduction in retention of BLS knowledge (p > 0.05) or BLS skills (p < 0.05) in the intervention group, but there was a significant reduction in both (p < 0.05) in the control group. We found no significant reduction in retention of ALS knowledge in the control group (p > 0.05), but there was a significant reduction in the intervention group (p < 0.05). There was no significant decay of ALS skills in both groups (p < 0.05).

DISCUSSION: This is the first study to demonstrate that combined spacing and testing could be highly effective for complex skills simulation training to increase retention after three months.}, } @article {pmid39535924, year = {2024}, author = {Hannestad, J and Smith, S and Lam, A and Hurt, J and Harada, N and Kim, R and Das, A and Brunello, J and Whitaker, G and Chalmers, D and Senjoti, F and Lin, W and Coghill, J and Bansal, Y and Sidhu, S and Zann, V and Liu, E}, title = {A randomized, placebo-controlled first-in-human study of oral TQS-168 in healthy volunteers: Assessment of safety, tolerability, pharmacokinetics, pharmacodynamics, and food effect.}, journal = {Clinical and translational science}, volume = {17}, number = {11}, pages = {e70064}, pmid = {39535924}, issn = {1752-8062}, mesh = {Humans ; Male ; *Food-Drug Interactions ; Adult ; Administration, Oral ; *Healthy Volunteers ; Young Adult ; Middle Aged ; Area Under Curve ; Double-Blind Method ; Dose-Response Relationship, Drug ; Methylcellulose/administration & dosage/analogs & derivatives/chemistry ; Spray Drying ; Suspensions ; Cross-Over Studies ; Placebos/administration & dosage ; }, abstract = {TQS-168, a first-in-class small-molecule inducer of peroxisome proliferator-activated receptor gamma coactivator 1-alpha gene expression, is in development for the treatment of amyotrophic lateral sclerosis. A single-ascending-dose (SAD) and multiple-ascending-dose (MAD) study of TQS-168 was carried out in healthy male subjects to investigate safety, tolerability, pharmacokinetics (PK), food effect, and preliminary pharmacodynamic effects (PD). Since solubility enhancement could be beneficial, assessment of three formulations was incorporated into the study using an integrated rapid manufacturing and clinical testing approach. Dosing in the SAD part was initiated with a crystalline methylcellulose (MC) suspension, and then spray-dried dispersion (SDD) and hot-melt extrusion (HME) suspensions were evaluated. The HME and SDD formulations showed two and fourfold higher exposure than the MC suspension, respectively, and the SDD formulation was selected for progression to subsequent SAD and MAD cohorts, in which there was further investigation of the food effect on exposure in addition to assessments of safety, tolerability, PK, and PD. Cmax and AUC plasma exposures of TQS-168 were supra-proportional at higher doses, irrespective of formulation. Median Tmax for TQS-168 occurred between 0.5 and 4.0 h post-dose and occurred later with higher doses. Geometric mean half-lives (T1/2) for TQS-168 were independent of formulation and food, ranging from 3.2 to 10.5 h following single doses and 4.1 to 7.3 h following multiple doses. Food blunted TQS-168 Cmax but had minimal impact on AUC. TQS-168 was considered to be safe and generally well tolerated following single and multiple oral doses. The SDD formulation was selected for future patient studies.}, } @article {pmid39534418, year = {2024}, author = {Wang, WL and Tam, PKH and Chen, Y}, title = {Abnormally activated wingless/integrated signaling modulates tumor-associated macrophage polarization and potentially promotes hepatocarcinoma cell growth.}, journal = {World journal of gastroenterology}, volume = {30}, number = {41}, pages = {4490-4495}, pmid = {39534418}, issn = {2219-2840}, mesh = {Humans ; *Carcinoma, Hepatocellular/pathology/metabolism ; *Liver Neoplasms/pathology/metabolism ; *Tumor-Associated Macrophages/metabolism/immunology ; *Cell Proliferation ; *Wnt Signaling Pathway ; *Tumor Microenvironment ; Cell Movement ; Animals ; Disease Progression ; Macrophage Activation ; }, abstract = {In this article, we comment on the article by Huang et al. The urgent development of new therapeutic strategies targeting macrophage polarization is critical in the fight against liver cancer. Tumor-associated macrophages (TAMs), primarily of the M2 subtype, are instrumental in cellular communication within the tumor microenvironment and are influenced by various signaling pathways, including the wingless/integrated (Wnt) pathway. Activation of the Wnt signaling pathway is pivotal in promoting M2 TAMs polarization, which in turn can exacerbate hepatocarcinoma cell proliferation and migration. This manuscript emphasizes the burgeoning significance of the Wnt signaling pathway and M2 TAMs polarization in the pathogenesis and progression of liver cancer, highlighting the potential therapeutic benefits of inhibiting the Wnt pathway. Lastly, we point out areas in Huang et al's study that require further research, providing guidance and new directions for similar studies.}, } @article {pmid39525702, year = {2024}, author = {Ravichandran, VV and Coleman, E and Brown, A and Boh, E}, title = {Response to Rodríguez-Cuadrado et al's "Clinical, histopathologic, immunohistochemical, and electron microscopic findings in cutaneous monkeypox: A multicenter retrospective case series in Spain".}, journal = {JAAD case reports}, volume = {53}, number = {}, pages = {149-150}, pmid = {39525702}, issn = {2352-5126}, } @article {pmid39524179, year = {2024}, author = {Trinh, QD and Mai, HN and Pham, DT}, title = {Application of mesenchymal stem cells for neurodegenerative diseases therapy discovery.}, journal = {Regenerative therapy}, volume = {26}, number = {}, pages = {981-989}, pmid = {39524179}, issn = {2352-3204}, abstract = {Neurodegenerative diseases are central or peripheral nervous system disorders associated with progressive brain cell degeneration. Common neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis have been widely studied. However, current therapeutics only reduce the symptoms and do not ameliorate the pathogenesis of these diseases. Recent studies suggested the roles of neuroinflammation, apoptosis, and oxidative stress in neurodegenerative diseases. Mesenchymal stem cells (MSCs) exert anti-apoptotic, anti-inflammatory, and antioxidative effects. Therefore, investigating the effects of MSCs and their applications may lead to the discovery of more effective therapies for neurodegenerative diseases. In this study, we review different approaches used to identify therapies for neurodegenerative diseases using MSCs.}, } @article {pmid39534515, year = {2024}, author = {Watanabe, S and Sekiguchi, K and Suehiro, H and Yoshikawa, M and Noda, Y and Kamiyama, N and Matsumoto, R}, title = {Decreased diaphragm moving distance measured by ultrasound speckle tracking reflects poor prognosis in amyotrophic lateral sclerosis.}, journal = {Clinical neurophysiology practice}, volume = {9}, number = {}, pages = {252-260}, pmid = {39534515}, issn = {2467-981X}, abstract = {OBJECTIVE: Decreased cephalocaudal diaphragm movement may indicate respiratory dysfunction in amyotrophic lateral sclerosis (ALS). We aimed to evaluate diaphragm function in ALS using ultrasound speckle tracking, an image-analysis technology that follows similar pixel patterns.

METHODS: We developed an offline application that tracks pixel patterns of recorded ultrasound video images using speckle-tracking methods. Ultrasonography of the diaphragm movement during spontaneous quiet respiration was performed on 19 ALS patients and 21 controls to measure the diaphragm moving distance (DMD) in the cephalocaudal direction during a single respiration. We compared respiratory function measures and analyzed the relationship between the clinical profiles and DMD.

RESULTS: DMD was significantly lower in ALS patients than in the control group (0.6 ± 1.4 mm vs 2.2 ± 2.2 mm, p < 0.01) and positively correlated with phrenic nerve compound motor action potential amplitude (R = 0.63, p = 0.01). DMD was negatively correlated with the change in the ALS Functional Rating Scale-Revised scores per month after the exam (R = -0.61, p = 0.02), and those with a larger rate of decline had a significantly lower DMD (p = 0.03).

CONCLUSIONS: Diaphragm ultrasound speckle tracking enabled the detection of diaphragm dysfunction in ALS.

SIGNIFICANCE: Diaphragm ultrasound speckle tracking may be useful for predicting prognosis.}, } @article {pmid39534483, year = {2024}, author = {Sbarigia, C and Rome, S and Dini, L and Tacconi, S}, title = {New perspectives of the role of skeletal muscle derived extracellular vesicles in the pathogenesis of amyotrophic lateral sclerosis: the 'dying back' hypothesis.}, journal = {Journal of extracellular biology}, volume = {3}, number = {11}, pages = {e70019}, pmid = {39534483}, issn = {2768-2811}, abstract = {Amyotrophic lateral sclerosis (ALS), is a progressive neurodegenerative disease that affects nerve cells in the brain and the spinal cord, and is characterized by muscle weakness, paralysis and ultimately, respiratory failure. The exact causes of ALS are not understood, though it is believed to combine genetic and environmental factors. Until now, it was admitted that motor neurons (MN) in the brain and spinal cord degenerate, leading to muscle weakness and paralysis. However, as ALS symptoms typically begin with muscle weakness or stiffness, a new hypothesis has recently emerged to explain the development of the pathology, that is, the 'dying back hypothesis', suggesting that this degeneration starts at the connections between MN and muscles, resulting in the loss of muscle function. Over time, this damage extends along the length of the MN, ultimately affecting their cell bodies in the spinal cord and brain. While the dying back hypothesis provides a potential framework for understanding the progression of ALS, the exact mechanisms underlying the disease remain complex and not fully understood. In this review, we are positioning the role of extracellular vesicles as new actors in ALS development.}, } @article {pmid39534022, year = {2024}, author = {Li, Y and Bhinge, A and Inoue, S and Garcia, G}, title = {Editorial: Noncoding RNAs in neurodegenerative disorders: from current insights and future directions to translational modeling and therapeutic approaches.}, journal = {Frontiers in neuroscience}, volume = {18}, number = {}, pages = {1497673}, pmid = {39534022}, issn = {1662-4548}, } @article {pmid39531950, year = {2025}, author = {Kacem, I and Sghaier, I and Ben Rhouma, H and Ratti, A and Ticozzi, N and Silani, V and Gouider-Khouja, N and Gouider, R}, title = {Association of Amyotrophic Lateral Sclerosis and Dopa-responsive dystonia in a Tunisian patient.}, journal = {Parkinsonism & related disorders}, volume = {130}, number = {}, pages = {107171}, doi = {10.1016/j.parkreldis.2024.107171}, pmid = {39531950}, issn = {1873-5126}, mesh = {Adult ; Humans ; *Amyotrophic Lateral Sclerosis/genetics/complications ; *Dystonic Disorders/genetics/drug therapy ; GTP Cyclohydrolase/genetics ; Tunisia ; }, abstract = {Dopa-responsive dystonia (DRD) is an autosomal dominant disease with parkinsonian and dystonic symptoms caused by GCH1 gene pathogenic variants affecting dopamine synthesis. The present case report is the first to link DRD with childhood-onset with ALS, suggesting that complex inheritance patterns in the North African population may contribute to multiple disorders.}, } @article {pmid39531940, year = {2024}, author = {Pioro, EP and Brooks, BR and Liu, Y and Zhang, J and Apple, S}, title = {Efficacy of Radicava® IV (intravenous edaravone) in subjects with differing trajectories of disease progression in amyotrophic lateral sclerosis: Use of a novel statistical approach for post hoc analysis of a pivotal phase 3 clinical trial.}, journal = {Journal of the neurological sciences}, volume = {467}, number = {}, pages = {123290}, doi = {10.1016/j.jns.2024.123290}, pmid = {39531940}, issn = {1878-5883}, mesh = {Humans ; *Edaravone/therapeutic use/administration & dosage ; *Amyotrophic Lateral Sclerosis/drug therapy ; *Disease Progression ; Male ; Female ; Middle Aged ; Aged ; Treatment Outcome ; Double-Blind Method ; Free Radical Scavengers/therapeutic use/administration & dosage ; Administration, Intravenous ; }, abstract = {INTRODUCTION: Subjects with amyotrophic lateral sclerosis (ALS) treated with Radicava® (edaravone) IV (intravenous; Mitsubishi Tanabe Pharma America [MTPA], hereafter "MTPA IV edaravone") in Study MCI186-19 had a significantly slower physical functional decline vs placebo-treated subjects as measured by the revised ALS Functional Rating Scale (ALSFRS-R) and analyzed by the linear mixed model for repeated measures (MMRM). This Study 19 post hoc analysis of MTPA IV edaravone-treated and placebo-treated subjects evaluated linear and nonlinear latent class mixed models defining trajectories based on identifying the model with the lowest Bayesian information criterion. The best model differentiated 4 nonlinear trajectories in ALS subjects. ALSFRS-R total score in MTPA IV edaravone-treated and placebo-treated subjects was evaluated for these 4 nonlinear latent class trajectory groups.

METHODS: Disease trajectories of MCI186-19 MTPA IV edaravone-treated or placebo-treated ALS subjects who completed the double-blind period were investigated using latent class analysis (LCA) statistical models to identify potential unique nonlinear ALSFRS-R disease trajectories.

RESULTS: ALSFRS-R trajectories revealed 4 unique nonlinear trajectory latent classes per treatment group in MTPA IV edaravone-treated and placebo-treated ALS subjects completing the MCI186-19 double-blind period. Latent classes 2-4 had statistically significant slowing of ALSFRS-R total score decline in the predicted nonlinear trajectories of MTPA IV edaravone-treated vs placebo-treated ALS subjects.

CONCLUSIONS: This post hoc analysis suggests MTPA IV edaravone treatment results in slower ALSFRS-R decline vs placebo in most predicted nonlinear trajectories. LCA is a novel approach that may benefit future trial analyses.}, } @article {pmid39529471, year = {2025}, author = {Trojsi, F and Canna, A and Sharbafshaaer, M and di Nardo, F and Canale, F and Passaniti, C and Pirozzi, MA and Silvestro, M and Orologio, I and Russo, A and Cirillo, M and Tessitore, A and Siciliano, M and Esposito, F}, title = {Brain neurovascular coupling in amyotrophic lateral sclerosis: Correlations with disease progression and cognitive impairment.}, journal = {European journal of neurology}, volume = {32}, number = {1}, pages = {e16540}, pmid = {39529471}, issn = {1468-1331}, support = {NRRP project MNESYS (PE0000006, to NT)//Ministero dell'Istruzione, dell'Università e della Ricerca/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology/diagnostic imaging ; Male ; Female ; *Disease Progression ; Middle Aged ; *Cognitive Dysfunction/physiopathology/etiology/diagnostic imaging ; Aged ; *Magnetic Resonance Imaging ; *Neurovascular Coupling/physiology ; Adult ; *Brain/physiopathology/diagnostic imaging/blood supply ; Nerve Net/diagnostic imaging/physiopathology ; Default Mode Network/physiopathology/diagnostic imaging ; }, abstract = {BACKGROUND AND PURPOSE: 'Neurovascular coupling' (NVC) alterations, assessing the interplay between local cerebral perfusion and neural activity within a given brain region or network, may reflect neurovascular unit impairment in amyotrophic lateral sclerosis (ALS). The aim was to explore NVC as a correlation between the functional connectivity and cerebral blood flow within the large-scale resting-state functional magnetic resonance imaging brain networks in a sample of ALS patients compared to healthy controls (HCs).

METHODS: Forty-eight ALS patients (30 males; mean age 60.64 ± 9.62 years) and 32 HC subjects (14 males; mean age 55.06 ± 16 years) were enrolled and underwent 3 T magnetic resonance imaging. ALS patients were screened by clinical and neuropsychological scales and were retrospectively classified as very fast progressors (VFPs), fast progressors and slow progressors (SPs).

RESULTS: Neurovascular coupling reduction within the default mode network (DMN) (p = 0.005) was revealed in ALS patients compared to HCs, observing, for this network, significant NVC differences between VFP and SP groups. Receiver operating characteristic curve analysis showed that impaired NVC in the DMN at baseline best discriminated VFPs and SPs (area under the curve 75%). Significant correlations were found between NVC and the executive (r = 0.40, p = 0.01), memory (r = 0.32, p = 0.04), visuospatial ability (r = 0.40, p = 0.01) and non-ALS-specific (r = 0.40, p = 0.01) subscores of the Edinburgh Cognitive and Behavioural ALS Screen.

CONCLUSIONS: The reduction of brain NVC in the DMN may reflect largely distributed abnormalities of the neurovascular unit. NVC alterations in the DMN could play a role in anticipating a faster clinical progression in ALS patients, aiding patient selection and monitoring during clinical trials.}, } @article {pmid39528814, year = {2024}, author = {Ovchinnikova, LA and Dzhelad, SS and Simaniv, TO and Zakharova, MN and Lomakin, YA and Gabibov, AG and Illarioshkin, SN}, title = {Development of a Panel of Biomarkers for Differential Diagnosis of Multiple Sclerosis.}, journal = {Doklady. Biochemistry and biophysics}, volume = {519}, number = {1}, pages = {593-596}, pmid = {39528814}, issn = {1608-3091}, mesh = {Humans ; Biomarkers/metabolism/blood ; Diagnosis, Differential ; *Multiple Sclerosis/diagnosis/metabolism/blood ; Amyotrophic Lateral Sclerosis/diagnosis ; Male ; Female ; Middle Aged ; Neuromyelitis Optica/diagnosis/blood ; Adult ; }, abstract = {Demyelinating diseases are a group of heterogeneous pathologies that affect the nervous system and reduce the quality of life. One of such diseases is multiple sclerosis (MS), an inflammatory autoimmune neurodegenerative disease of the central nervous system (CNS). At the initial stages, MS can mimic some infectious, neoplastic, genetic, metabolic, vascular, and other pathologies. Accurate differential diagnosis of this disease is important to improve the quality of life of patients and reduce possible irreversible damage to the central nervous system. In this work, we confirmed the possibility of using our previously proposed candidate panel of MS biomarkers to distinguish MS from neuromyelitis optica spectrum disorder (NMOSD) and amyotrophic lateral sclerosis (ALS). We have shown that our proposed panel (SPTAN1601-644 + PRX451-494 + PTK6301-344 + LMP1285-330) allows us to distinguish MS from ALS (AUC = 0.796) and NMOSD (AUC = 0.779).}, } @article {pmid39526716, year = {2024}, author = {Šljivo, A and Jevtić, T and Siručić, I and Terzić-Salihbašić, S and Abdulkhaliq, A and Reiter, L and Salihbašić, F and Bečar-Alijević, A and Alijević, A and Dadić, I and Gavrankapetanović, F}, title = {Out-of-hospital cardiac arrest (OHCA) in Bosnia and Herzegovina in the period 2018-2022: current trends, usage of automated external defibrillators (AED) and bystanders' involvement.}, journal = {Medicinski glasnik : official publication of the Medical Association of Zenica-Doboj Canton, Bosnia and Herzegovina}, volume = {21}, number = {2}, pages = {267-273}, doi = {10.17392/1719-21-2}, pmid = {39526716}, issn = {1840-2445}, abstract = {AIM: To investigate out-of-hospital cardiac arrest (OHCA) trend, provided advanced life support (ALS) measures, automated external defibrillator (AEDs) utilization and bystanders' involvement in cardiopulmonary resuscitation (CPR) during OHCA incidents.

METHODS: This cross-sectional study encompassed data pertaining to all OHCA incidents attended to by the Emergency Medical Service of Canton Sarajevo, Bosnia and Herzegovina, covering the period from January 2018 to December 2022.

RESULTS: Among a total of 1131 OHCA events, 236 (20.8 %) patients achieved return of spontaneous circulation (ROSC); there were 175 (74.1%) males and 61 (25.9%) females. The OHCA incidence was 54/100,000 inhabitants per year. After a 30-day period post-ROSC, 146 (61.9%) patients fully recovered, while 90 (38.1%) did not survive during this timeframe. Younger age (p<0.05), initial rhythm of ventricular fibrillation (VF) or pulseless ventricular tachycardia (VT) (p<0.05), and faster emergency medical team (EMT) response time (p<0.05) were significantly associated with obtaining ROSC. Only 38 (3.3%) OHCA events were assisted by bystanders, who were mostly medical professionals, 25 (65.7%), followed by close family members, 13 (34.3%). There was no report of AED usage.

CONCLUSION: This follow-up study showed less ROSC achievement, similar bystanders' involvement, similar factors associated with achieving ROSC (age, EMT response time), and a decline in OHCA events (especially in year 2021 and 2022) compared to our previous study (2015-2019). There was an extremely low rate of bystander engagement and no AEDs usage. Governments and health organizations must swiftly improve public awareness, promote better practice (basic life support), and actively encourage bystander participation.}, } @article {pmid39523617, year = {2024}, author = {Iguchi, Y and Katsuno, M}, title = {[Current Status of Drug Development for Amyotrophic Lateral Sclerosis].}, journal = {Brain and nerve = Shinkei kenkyu no shinpo}, volume = {76}, number = {11}, pages = {1241-1249}, doi = {10.11477/mf.1416202766}, pmid = {39523617}, issn = {1881-6096}, mesh = {*Amyotrophic Lateral Sclerosis/drug therapy ; Humans ; *Drug Development ; Clinical Trials as Topic ; Animals ; Riluzole/therapeutic use ; Neuroprotective Agents/therapeutic use ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive and fatal disease of motor neuron. Although riluzole and edaravone have been approved for the treatment of ALS, it remains a lethal disease that causes rapid motor impairment, and there is an urgent need to develop more effective treatments. Advances in understanding the pathomechanisms of ALS, efficient clinical trial design, and research support programs have led to many clinical trials for ALS both domestically and internationally.}, } @article {pmid39523616, year = {2024}, author = {Ishiguro, T and Nagata, T and Yokota, T}, title = {[Current Landscape of Tofersen in SOD-1-associated Amyotrophic Lateral Sclerosis].}, journal = {Brain and nerve = Shinkei kenkyu no shinpo}, volume = {76}, number = {11}, pages = {1233-1239}, doi = {10.11477/mf.1416202765}, pmid = {39523616}, issn = {1881-6096}, mesh = {*Amyotrophic Lateral Sclerosis/genetics/therapy ; Humans ; *Superoxide Dismutase-1/genetics ; Mutation ; }, abstract = {Since the identification, in 1993, of the causative gene for familial amyotrophic lateral sclerosis (ALS), which is associated with SOD1 mutations, research has focused on the pathogenesis and therapeutics of ALS for more than 30 years. Tofersen, a highly anticipated gene-specific therapy that has been aligned with the disease-specific pathology, has been approved for marketing by the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) However, as significant data on tofersen's safety and efficacy are required, the evaluation of this treatment is ongoing. This paper introduces the current clinical and commercial status of Tofersen, along with expectations for its approval in Japan.}, } @article {pmid39523615, year = {2024}, author = {Ogino, M}, title = {[Palliative Care for Persons with Amyotrophic Lateral Sclerosis].}, journal = {Brain and nerve = Shinkei kenkyu no shinpo}, volume = {76}, number = {11}, pages = {1225-1232}, doi = {10.11477/mf.1416202764}, pmid = {39523615}, issn = {1881-6096}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy ; Analgesics, Opioid/administration & dosage ; Japan ; *Palliative Care ; }, abstract = {Palliative care in Japan is available mainly for patients with cancer, and palliative care specialists do not have sufficient experience with management of palliation in persons with amyotrophic lateral sclerosis (ALS). Treatment of ALS symptoms is an important component of palliative care, and it is important that neurologists and home care physicians familiarize themselves with palliative care for ALS in consultation with palliative care specialists. Notably, the use of opioids at the end of life differs from that of pain relief for cancer. Physicians should be mindful that opioids are not a perfect solution for palliative care of persons with ALS.}, } @article {pmid39523614, year = {2024}, author = {Yamakawa, I and Urushitani, M}, title = {[Gold Coast Criteria: A New Diagnostic Paradigm in the Era of Disease-Modifying Therapy for Amyotrophic Lateral Sclerosis].}, journal = {Brain and nerve = Shinkei kenkyu no shinpo}, volume = {76}, number = {11}, pages = {1217-1223}, doi = {10.11477/mf.1416202763}, pmid = {39523614}, issn = {1881-6096}, mesh = {*Amyotrophic Lateral Sclerosis/diagnosis/drug therapy ; Humans ; }, abstract = {Significant progress has been made in the development of disease-modifying drugs for amyotrophic lateral sclerosis (ALS), with the introduction of tofersen, an antisense oligonucleotide drug for familial ALS, marking a turning point in the treatment. These drugs are most effective when administered early in the disease course, highlighting the need for improved diagnostic sensitivity. The 2020 Gold Coast Diagnostic Criteria allow ALS diagnosis in cases without upper motor neuron symptoms, potentially increasing early detection rates. However, careful differential diagnoses are necessary when applying these criteria to maintain diagnostic specificity. This review outlines the key points to consider when using the Gold Coast Criteria, balancing the need for an early diagnosis with caution to avoid overdiagnosis.}, } @article {pmid39523613, year = {2024}, author = {Fukutake, T}, title = {[Diagnosis, Notification, and Managements of ALS: A Personal Perspective from 40 years of Experience as a Clinical Neurologist].}, journal = {Brain and nerve = Shinkei kenkyu no shinpo}, volume = {76}, number = {11}, pages = {1205-1216}, doi = {10.11477/mf.1416202762}, pmid = {39523613}, issn = {1881-6096}, mesh = {*Amyotrophic Lateral Sclerosis/diagnosis/therapy ; Humans ; *Neurologists ; Female ; Middle Aged ; Male ; Aged ; }, abstract = {This narrative summary presents the author's 40-year experience as a clinical neurologist who treated patients with amyotrophic lateral sclerosis (ALS). Five representative cases from the author's first 20 years at Chiba University Hospital and its affiliated hospitals were selected, including a patient of respiratory-onset who was ignorantly extubated by a female relative for patient's distress to the intratracheal tube. Based on the latter 20 years of experience at the author's current hospital, the author first describes a famous patient with ALS who was being treated at this medical center before the author was assigned to this hospital and fought against ALS for 31 years before eventually succumbing to total locked-in syndrome. Thereafter, the author has summarized the ages, sex, phenotypes, comorbidities, responses to the available treatment options, and total number of years that have elapsed for the 24 patients that the author initially examined in the outpatient clinic. In terms of diagnostic delay, the author describes "foot drop" in patients who developed lower limb symptoms, and hoarseness in those who developed bulbar palsy. Furthermore, the author discusses issues regarding family caregiving capacity, patient's and families' understanding of notification, and medical management (i.e., medications, rehabilitation for ADL, nutrition and respiration, complications of frontotemporal dementia, and medical cooperation with other clinics and hospitals).}, } @article {pmid39522728, year = {2025}, author = {Lauck, KC and Narayanan, D and Tolkachjov, SN}, title = {Regarding response to Narayanan et al's "Adverse events in cemiplimab therapy for locally advanced or metastatic cSCC: A global propensity-matched retrospective cohort study".}, journal = {Journal of the American Academy of Dermatology}, volume = {92}, number = {3}, pages = {e59-e60}, doi = {10.1016/j.jaad.2024.10.059}, pmid = {39522728}, issn = {1097-6787}, } @article {pmid39522725, year = {2025}, author = {Tsai, SY}, title = {Response to Narayanan et al's "Adverse events in cemiplimab therapy for locally advanced or metastatic cSCC: A global propensity-matched retrospective cohort study".}, journal = {Journal of the American Academy of Dermatology}, volume = {92}, number = {3}, pages = {e57}, doi = {10.1016/j.jaad.2024.08.085}, pmid = {39522725}, issn = {1097-6787}, } @article {pmid39522723, year = {2025}, author = {Nardone, V and Esposito, A and D'Ippolito, E and Argenziano, G and Reginelli, A and Troiani, T}, title = {Response to Sajid et al's "Response to Valerio Nardone et al's 'Previous radiotherapy increases the efficacy of cemiplimab in the treatment of locally advanced and metastatic cutaneous squamous cell carcinoma: A retrospective analysis'".}, journal = {Journal of the American Academy of Dermatology}, volume = {92}, number = {3}, pages = {e55-e56}, doi = {10.1016/j.jaad.2024.10.058}, pmid = {39522723}, issn = {1097-6787}, } @article {pmid39522697, year = {2024}, author = {Gao, L and Yang, XN and Dong, YX and Han, YJ and Zhang, XY and Zhou, XL and Liu, Y and Liu, F and Fang, JS and Ji, JL and Gao, ZR and Qin, XM}, title = {The potential therapeutic strategy in combating neurodegenerative diseases: Focusing on natural products.}, journal = {Pharmacology & therapeutics}, volume = {264}, number = {}, pages = {108751}, doi = {10.1016/j.pharmthera.2024.108751}, pmid = {39522697}, issn = {1879-016X}, mesh = {Humans ; *Biological Products/therapeutic use/pharmacology ; *Neurodegenerative Diseases/drug therapy ; Animals ; *Neuroprotective Agents/therapeutic use/pharmacology ; }, abstract = {Neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic lateral sclerosis (ALS), Huntington disease (HD), and Multiple sclerosis (MS), pose a significant global health challenge due to their intricate pathology and limited therapeutic interventions. Natural products represent invaluable reservoirs for combating these neurodegenerative diseases by targeting key pathological hallmarks such as protein aggregation, synaptic dysfunction, aberrant proteostasis, cytoskeletal abnormalities, altered energy homeostasis, inflammation, and neuronal cell death. This review provides an in-depth analysis of the mechanisms and therapeutic targets of natural products for their neuroprotective effects. Furthermore, it elucidates the current progress of clinical trials investigating the potential of natural products in delaying neurodegeneration. The objective of this review is to enhance the comprehension of natural products in the prevention and treatment of neurodegenerative diseases, offering new insights and potential avenues for future pharmaceutical research.}, } @article {pmid39522672, year = {2025}, author = {Shapiro, O and Woods, C and Gleixner, AM and Sannino, S and Ngo, M and McDaniels, MD and Wipf, P and Hukriede, NA and Donnelly, CJ and Brodsky, JL}, title = {Assays to measure small molecule Hsp70 agonist activity in vitro and in vivo.}, journal = {Analytical biochemistry}, volume = {697}, number = {}, pages = {115712}, pmid = {39522672}, issn = {1096-0309}, support = {U54 DK137329/DK/NIDDK NIH HHS/United States ; R01 DK112652/DK/NIDDK NIH HHS/United States ; P30 DK079307/DK/NIDDK NIH HHS/United States ; R01 DK069403/DK/NIDDK NIH HHS/United States ; R35 GM131732/GM/NIGMS NIH HHS/United States ; R21 NS133676/NS/NINDS NIH HHS/United States ; R01 NS127187/NS/NINDS NIH HHS/United States ; R01 NS105756/NS/NINDS NIH HHS/United States ; R01 HD053287/HD/NICHD NIH HHS/United States ; }, mesh = {*HSP70 Heat-Shock Proteins/metabolism/agonists ; Animals ; *Zebrafish ; Humans ; Small Molecule Libraries/pharmacology/chemistry ; Optogenetics/methods ; DNA-Binding Proteins/agonists/metabolism ; }, abstract = {Hsp70 prevents protein aggregation and is cytoprotective, but sustained Hsp70 overexpression is problematic. Therefore, we characterized small molecule agonists that augment Hsp70 activity. Because cumbersome assays were required to assay agonists, we developed cell-based and in vivo assays in which disease-associated consequences of Hsp70 activation can be quantified. One assay uses an optogenetic system in which the formation of TDP-43 inclusions can be controlled, and the second assay employs a zebrafish model for acute kidney injury (AKI). These complementary assays will facilitate future work to identify new Hsp70 agonists as well as optimized agonist derivatives.}, } @article {pmid39521994, year = {2024}, author = {Liang, H and Zhou, X and Zhang, J and Xu, W and Liu, Y and Wang, X and Hu, Y and Xu, R and Li, X}, title = {The therapeutic potential of Apigenin in amyotrophic lateral sclerosis through ALDH1A2/Nrf2/ARE signaling.}, journal = {Molecular medicine (Cambridge, Mass.)}, volume = {30}, number = {1}, pages = {206}, pmid = {39521994}, issn = {1528-3658}, support = {81960244//National Natural Science Foundation of China/ ; 20212BAB216026//Jiangxi Natural Science Foundation/ ; 202110016//Science and Technology Plan of Jiangxi Provincial Health Commission/ ; 2022B975//Science and Technology Plan of Jiangxi Provincial Administration of Traditional Chinese Medicine/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/drug therapy/metabolism/genetics ; Animals ; *Apigenin/pharmacology/therapeutic use ; Mice ; *Signal Transduction/drug effects ; *Mice, Transgenic ; *Disease Models, Animal ; *NF-E2-Related Factor 2/metabolism/genetics ; Oxidative Stress/drug effects ; Aldehyde Dehydrogenase 1 Family/metabolism/genetics ; Humans ; Apoptosis/drug effects ; Retinal Dehydrogenase/metabolism/genetics ; Cell Line ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by motor neuron loss leading to muscle weakness and atrophy. Apigenin (APG), known for its antioxidant properties, holds potential as a therapeutic compound in ALS.

METHODS: We used the Tg(SOD1*G93A)1Gur/J transgenic mouse model of ALS to investigate the therapeutic effects of APG. Key measured included motor function via the ALSTDI score, molecular markers of oxidative stress (OS) and apoptosis in spinal cord tissues. Techniques used included pathological, Western blotting, flow cytometry, and qRT-PCR to assess the effect of ALDH1A2.

RESULTS: APG treatment attenuated weight loss and improved motor function scores in ALS mice compared to untreated ALS models. Molecular analyses revealed a significant upregulation of ALDH1A2 in APG-treated groups, along with a reduction in markers of OS and apoptosis. In vitro studies in NSC34 cells further confirmed the protective effects of APG against SOD1*G93A mutation-induced cytotoxicity. In addition, suppression of ALDH1A2 by shRNA exacerbated disease markers that were ameliorated by APG treatment.

CONCLUSIONS: Our results suggest that APG attenuates the progression of ALS pathology by regulating OS and apoptosis through ALDH1A2. These results support further investigation of APG as a potential therapeutic agent for the treatment of ALS.}, } @article {pmid39521135, year = {2025}, author = {Sajid, SL and Ur Rehman, MA and Sajid, SA and Shahid, N}, title = {Response to Valerio Nardone et al's "Previous radiotherapy increases the efficacy of cemiplimab in the treatment of locally advanced and metastatic cutaneous squamous cell carcinoma: A retrospective analysis".}, journal = {Journal of the American Academy of Dermatology}, volume = {92}, number = {3}, pages = {e53-e54}, doi = {10.1016/j.jaad.2024.08.084}, pmid = {39521135}, issn = {1097-6787}, } @article {pmid39520580, year = {2024}, author = {Hyldgaard Andersen, S and Harsløf, S and Tøttrup, A}, title = {Laparoscopic ileopexy for afferent loop syndrome after restorative proctocolectomy-a retrospective case series.}, journal = {International journal of colorectal disease}, volume = {39}, number = {1}, pages = {180}, pmid = {39520580}, issn = {1432-1262}, mesh = {Humans ; *Proctocolectomy, Restorative/adverse effects ; *Laparoscopy/adverse effects ; Female ; Male ; Retrospective Studies ; Middle Aged ; Adult ; *Afferent Loop Syndrome/surgery/etiology ; *Ileum/surgery ; Aged ; Treatment Outcome ; Postoperative Complications/etiology/surgery ; }, abstract = {BACKGROUND: To study the effect of laparoscopic ileopexy in patients with afferent-loop syndrome (ALS) after restorative proctocolectomy (RP).

METHOD: Ileopexy has been the treatment of choice in patients with ALS for the last 5 years at our department. All patients who had undergone ileopexy for ALS between January 2019 and August 2023 were identified. Data were extracted from the medical records. All patients were contacted and asked standardized questions regarding symptoms of ALS. A symptom score was calculated and compared before surgery and at the last follow-up.

RESULTS: Ten patients, who had undergone ileopexy for ALS, were identified. Eight of these (80%) had been admitted with small bowel obstruction due to ALS. The remaining 2 patients had other symptoms indicative of ALS. In all patients, ileopexy was immediately effective in reducing symptoms. Symptoms recurred after 16.5 weeks (2-80) in 8 patients. Repeat laparoscopy showed that the ileopexy had slipped in 6 of these. Six had a new ileopexy with mesh. Later, one of these developed recurrent symptoms and had a new mesh ileopexy performed. No mesh complications were seen. Symptom score was reduced from 6.5 (1-9) to 2 (0-7) (p = 0.02) at the last follow-up.

CONCLUSIONS: In this study, ileopexy is effective in reducing symptoms of ALS after RP. In a high proportion of patients, it is necessary to use mesh to ensure long-term fixation of the ileum.}, } @article {pmid39520508, year = {2024}, author = {Larose, A and Miller, CCJ and Mórotz, GM}, title = {The lemur tail kinase family in neuronal function and disfunction in neurodegenerative diseases.}, journal = {Cellular and molecular life sciences : CMLS}, volume = {81}, number = {1}, pages = {447}, pmid = {39520508}, issn = {1420-9071}, mesh = {Humans ; *Neurodegenerative Diseases/pathology/metabolism/enzymology ; Animals ; *Neurons/metabolism/pathology ; Cyclin-Dependent Kinase 5/metabolism/genetics ; Signal Transduction ; Synapses/metabolism/pathology ; Protein-Tyrosine Kinases/metabolism/genetics ; Phosphorylation ; Axonal Transport ; Glycogen Synthase Kinase 3 beta/metabolism ; }, abstract = {The complex neuronal architecture and the long distance of synapses from the cell body require precisely orchestrated axonal and dendritic transport processes to support key neuronal functions including synaptic signalling, learning and memory formation. Protein phosphorylation is a major regulator of both intracellular transport and synaptic functions. Some kinases and phosphatases such as cyclin dependent kinase-5 (cdk5)/p35, glycogen synthase kinase-3β (GSK3β) and protein phosphatase-1 (PP1) are strongly involved in these processes. A primary pathological hallmark of neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis/frontotemporal dementia, is synaptic degeneration together with disrupted intracellular transport. One attractive possibility is that alterations to key kinases and phosphatases may underlie both synaptic and axonal transport damages. The brain enriched lemur tail kinases (LMTKs, formerly known as lemur tyrosine kinases) are involved in intracellular transport and synaptic functions, and are also centrally placed in cdk5/p35, GSK3β and PP1 signalling pathways. Loss of LMTKs is documented in major neurodegenerative diseases and thus can contribute to pathological defects in these disorders. However, whilst function of their signalling partners became clearer in modulating both synaptic signalling and axonal transport progress has only recently been made around LMTKs. In this review, we describe this progress with a special focus on intracellular transport, synaptic functions and neurodegenerative diseases.}, } @article {pmid39519213, year = {2024}, author = {Bova, V and Mannino, D and Capra, AP and Lanza, M and Palermo, N and Filippone, A and Esposito, E}, title = {CK and LRRK2 Involvement in Neurodegenerative Diseases.}, journal = {International journal of molecular sciences}, volume = {25}, number = {21}, pages = {}, pmid = {39519213}, issn = {1422-0067}, mesh = {Humans ; *Leucine-Rich Repeat Serine-Threonine Protein Kinase-2/metabolism/genetics ; *Neurodegenerative Diseases/metabolism/genetics ; Animals ; Mutation ; Phosphorylation ; Autophagy/genetics ; }, abstract = {Neurodegenerative diseases (NDDs) are currently the most widespread neuronal pathologies in the world. Among these, the most widespread are Alzheimer's disease (AD), dementia, Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD)-all characterized by a progressive loss of neurons in specific regions of the brain leading to varied clinical symptoms. At the basis of neurodegenerative diseases, an emerging role is played by genetic mutations in the leucine-rich repeat kinase 2 (LRRK2) gene that cause increased LRRK2 activity with consequent alteration of neuronal autophagy pathways. LRRK2 kinase activity requires GTPase activity which functions independently of kinase activity and is required for neurotoxicity and to potentiate neuronal death. Important in the neurodegeneration process is the upregulation of casein kinase (CK), which causes the alteration of the AMPK pathway by enhancing the phosphorylation of α-synuclein and huntingtin proteins, known to be involved in PD and HD, and increasing the accumulation of the amyloid-β protein (Aβ) for AD. Recent research has identified CK of the kinases upstream of LRRK2 as a regulator of the stability of the LRRK2 protein. Based on this evidence, this review aims to understand the direct involvement of individual kinases in NDDs and how their crosstalk may impact the pathogenesis and early onset of neurodegenerative diseases.}, } @article {pmid39519209, year = {2024}, author = {Firdaus, Z and Li, X}, title = {Epigenetic Explorations of Neurological Disorders, the Identification Methods, and Therapeutic Avenues.}, journal = {International journal of molecular sciences}, volume = {25}, number = {21}, pages = {}, pmid = {39519209}, issn = {1422-0067}, support = {DK129241 DK126662/GF/NIH HHS/United States ; }, mesh = {Humans ; *Epigenesis, Genetic ; *DNA Methylation ; Neurodegenerative Diseases/genetics/therapy ; Animals ; Nervous System Diseases/genetics/therapy ; Histones/metabolism/genetics ; Epigenomics/methods ; Histone Code/genetics ; }, abstract = {Neurodegenerative disorders are major health concerns globally, especially in aging societies. The exploration of brain epigenomes, which consist of multiple forms of DNA methylation and covalent histone modifications, offers new and unanticipated perspective into the mechanisms of aging and neurodegenerative diseases. Initially, chromatin defects in the brain were thought to be static abnormalities from early development associated with rare genetic syndromes. However, it is now evident that mutations and the dysregulation of the epigenetic machinery extend across a broader spectrum, encompassing adult-onset neurodegenerative diseases. Hence, it is crucial to develop methodologies that can enhance epigenetic research. Several approaches have been created to investigate alterations in epigenetics on a spectrum of scales-ranging from low to high-with a particular focus on detecting DNA methylation and histone modifications. This article explores the burgeoning realm of neuroepigenetics, emphasizing its role in enhancing our mechanistic comprehension of neurodegenerative disorders and elucidating the predominant techniques employed for detecting modifications in the epigenome. Additionally, we ponder the potential influence of these advancements on shaping future therapeutic approaches.}, } @article {pmid39518442, year = {2024}, author = {Laucius, O and Drūteika, J and Balnytė, R and Palačionytė, J and Ališauskienė, M and Petrikonis, K and Vaitkus, A}, title = {Phrenic Nerve Sonography Alterations in Patients with ALS: Insight with Clinical and Neurophysiological Findings.}, journal = {Journal of clinical medicine}, volume = {13}, number = {21}, pages = {}, pmid = {39518442}, issn = {2077-0383}, abstract = {Background: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder, and although the diagnosis is primarily based on clinical criteria, ENMG, as the "gold standard", does not always show detectable changes. Therefore, our study suggests that alterations in echogenicity and heterogeneity of the phrenic nerve (PN) may serve as potential additional diagnostic tools for ALS. Methods: Our study included 32 patients in the ALS group and 64 individuals in the control group. Each participant underwent an interview and completed questionnaires to collect clinical and demographic data, including age, gender, height, body mass index (BMI), hip and waist circumference, duration of illness, ALS-FRS-R score, comorbidities, and medication use. Ultrasound examinations of the PN were performed by two authors using a high-resolution "Philips EPIQ 7" ultrasound machine equipped with a linear 4-18 MHz transducer. The ALS group participants underwent PN sonography and conduction examinations, arterial blood gas (ABG) analysis, respiratory function tests (RFT), and electroneuromyography (ENMG). Results: The study demonstrated that the phrenic nerve is significantly smaller on both sides in patients with ALS compared to the control group (p < 0.01). Changes in the homogeneity and echogenicity of the PN were also observed on both sides. On the right side, 43.8% of the nerves showed heterogeneity, 40.6% were isoechoic, and 21.9% were hyperechoic. On the left side, 59.4% of the nerves exhibited heterogeneity, 34.4% were isoechoic, and 28.1% were hyperechoic. Moreover, sonography on both sides showed significant correlation with ALS-FRS-R, COMPASS-31, and ENMG results. Conclusions: Our study highlights the importance of phrenic nerve ultrasound as a promising supplementary diagnostic tool for ALS. The significant differences in phrenic nerve size, echogenicity, and homogeneity between patients with ALS and the control group demonstrate that ultrasound imaging can detect morphological changes in the phrenic nerve. Incorporating phrenic nerve ultrasound into routine diagnostic protocols could improve early detection, enhance disease monitoring, and offer a more comprehensive understanding of the neurodegenerative processes in ALS.}, } @article {pmid39517754, year = {2024}, author = {Ciou, TS and Lin, CH and Wang, CK}, title = {Airborne LiDAR Point Cloud Classification Using Ensemble Learning for DEM Generation.}, journal = {Sensors (Basel, Switzerland)}, volume = {24}, number = {21}, pages = {}, pmid = {39517754}, issn = {1424-8220}, abstract = {Airborne laser scanning (ALS) point clouds have emerged as a predominant data source for the generation of digital elevation models (DEM) in recent years. Traditionally, the generation of DEM using ALS point clouds involves the steps of point cloud classification or ground point filtering to extract ground points and labor-intensive post-processing to correct the misclassified ground points. The current deep learning techniques leverage the ability of geometric recognition for ground point classification. However, the deep learning classifiers are generally trained using 3D point clouds with simple geometric terrains, which decrease the performance of model inferencing. In this study, a point-based deep learning model with boosting ensemble learning and a set of geometric features as the model inputs is proposed. With the ensemble learning strategy, this study integrates specialized ground point classifiers designed for different terrains to boost classification robustness and accuracy. In experiments, ALS point clouds containing various terrains were used to evaluate the feasibility of the proposed method. The results demonstrated that the proposed method can improve the point cloud classification and the quality of generated DEMs. The classification accuracy and F1 score are improved from 80.9% to 92.2%, and 82.2% to 94.2%, respectively, by using the proposed methods. In addition, the DEM generation error, in terms of mean squared error (RMSE), is reduced from 0.318-1.362 m to 0.273-1.032 m by using the proposed ensemble learning.}, } @article {pmid39515011, year = {2024}, author = {Mauri, L and Taccaliti, F and Lingua, E}, title = {Modeling the interaction between wildfires and windthrows: A pilot case study for Italian Alps.}, journal = {Journal of environmental management}, volume = {371}, number = {}, pages = {123150}, doi = {10.1016/j.jenvman.2024.123150}, pmid = {39515011}, issn = {1095-8630}, mesh = {*Wildfires ; Italy ; *Forests ; Pilot Projects ; Models, Theoretical ; Ecosystem ; Wind ; }, abstract = {Wildland fires and windthrows represent relevant disturbances for forest ecosystems worldwide. In this context, especially for Italian catchments, the interaction between windthrows and changes in wildfire behaviour starting from ALS data processing is scarcely investigated. Therefore, this research aims to compute a multi-temporal analysis of the interaction between windthrows and wildfire behaviour in a forested area (Veneto region, northern Italy), recently affected by the renamed Vaia windstorm. The semi-empirical FlamMap model was applied, starting from ALS data processing implemented in R for mapping the spatial distribution of forest attributes and fuels within the catchment. The role of windthrows in altering wildfire behaviour was investigated considering ALS point clouds acquired before and after the occurrence of the storm Vaia. Digital Terrain Models (DTMs), Canopy Height Models (CHMs), topographic data and metrics describing forest structure were extracted from ALS data for both scenarios at 5 m resolution, to compare changes in wildfire behaviour over time. Differences in Rate of Spread (RoS), flame length (FL), midflame windspeed (WS) and arrival time (AT) were assessed, and their correlation with windstorm damages was investigated at the catchment detail. , An increase of RoS, FL, and WS greater than 30 m/min, 3 m and 1.1 m/s were respectively estimated in windthrown areas, as well as a decrease of AT greater than 30 min, attesting the key role of windthrows in altering wildfire behaviour over time. The correlation between windthrows and changes in wildfire attributes was finally modeled by computing regression analysis, with R[2] of 0.86, 0.93, 0.62, and 0.91 resulted for RoS, FL, WS and AT. This research represents a pilot case study for better detecting changes in wildfires behaviour due to windthrows occurrence, therefore proposing and carrying out effective planning and management strategies for disturbed forest stands over time.}, } @article {pmid39514515, year = {2024}, author = {Ohnari, K and Mafune, K and Adachi, H}, title = {Fasciculation potentials are related to the prognosis of amyotrophic lateral sclerosis.}, journal = {PloS one}, volume = {19}, number = {11}, pages = {e0313307}, pmid = {39514515}, issn = {1932-6203}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology/mortality/diagnosis ; Male ; Female ; Middle Aged ; Prognosis ; *Fasciculation/physiopathology/diagnosis ; *Electromyography ; Aged ; Retrospective Studies ; Disease Progression ; Adult ; Biomarkers/blood ; }, abstract = {Some prognostic biomarkers of amyotrophic lateral sclerosis (ALS) have been described; however, they are inadequate for satisfactorily predicting individual patient outcomes. Fasciculation potentials (FPs) on electromyography (EMG) are useful for the early diagnosis of ALS, and complex FPs are associated with shorter survival in ALS. In this study, we investigated the relationship between the proportion of muscles with FPs, biochemical markers, and the prognosis of ALS. 89 Patients with ALS were retrospectively classified into three groups based on the interval from onset to death or tracheostomy (less than 1 year: fast progression; from 1 year to less than 3 years: average progression; 3 years or more: slow progression). We performed statistical analysis of the electrophysiological findings, including the percentage of examined muscles with FPs, and biochemical markers evaluated on admission. Patients with fast ALS progression had a higher percentage of muscles with FPs (93.1% vs. 37.9%, P<0.001) and lower uric acid (UA) levels (male: 4.19 mg/dl vs 5.55 mg/dl, P<0.001; female: 3.71 mg/dl vs 5.41 mg/dl, P<0.001) than patients with slow progression. Survival curves demonstrated a relationship between these factors and the survival time in patients with ALS. Furthermore, UA levels were correlated with the percentage of muscles with FPs. Our electrophysiological findings suggest that ALS presents with multisystem neurological manifestations, and these manifestations differed among the groups classified by disease progression. The percentage of muscles with FPs on EMG and serum UA levels were especially associated with the prognosis of ALS.}, } @article {pmid39513379, year = {2025}, author = {Simkins, TJ and Kupfer, S and Malik, FI and Meng, L and Rudnicki, SA and Wei, J and Shefner, JM and Bowser, R}, title = {Plasma neurofilament analysis in VITALITY-ALS.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {26}, number = {1-2}, pages = {103-112}, doi = {10.1080/21678421.2024.2423707}, pmid = {39513379}, issn = {2167-9223}, mesh = {Humans ; Male ; Female ; Middle Aged ; *Amyotrophic Lateral Sclerosis/blood/drug therapy/diagnosis ; Double-Blind Method ; Disease Progression ; *Neurofilament Proteins/blood ; Aged ; Biomarkers/blood ; *Intermediate Filaments/metabolism ; Longitudinal Studies ; Adult ; }, abstract = {OBJECTIVE: To evaluate correlations between neurofilament (Nf) concentrations and clinical characteristics and disease progression using a large longitudinal dataset from VITALITY-ALS (ClinicalTrials.gov identifier: NCT02496767), a 48-week, randomized, double-blind, placebo-controlled clinical trial of tirasemtiv in people with ALS (pALS).

METHODS: Plasma was collected at baseline and every 8 weeks thereafter. Results were compared between treatment groups and evaluated by clinical characteristics and over time. Pearson's correlation coefficients (r) were calculated to evaluate associations between Nf concentrations and slow vital capacity (SVC), Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) score, and pre-study/in-study rates of disease progression (psRDP/isRDP).

RESULTS: Nf measurements were available from 101 placebo- and 161 tirasemtiv-treated people with ALS (pALS). There were no significant differences in Nf between placebo and tirasemtiv groups at any time point; further analyses grouped all samples. At baseline, Nf concentration did not differ by multiple clinical characteristics. Baseline Nf light chain (NfL) concentration correlated with the psRDP (r = 0.50, p < 0.001) and isRDP (r = 0.53, p < 0.0001). Phosphorylated Nf heavy chain (pNfH) demonstrated a similar, but less robust, pattern of results. Baseline Nf concentration correlated with change in SVC and ALSFRS-R score over time. Plasma pNfH concentration continuously decreased over time. There was no meaningful change in plasma NfL concentration over the study period.

CONCLUSIONS: In this large longitudinal study, baseline NfL concentration correlated with multiple markers of disease progression. The findings suggest Nfs show promise primarily as prognostic markers for pALS, particularly for those with rapid disease progression.}, } @article {pmid39513316, year = {2024}, author = {Yadav, H and Malviya, R and Kaushik, N and Sridhar, SB}, title = {Therapeutic Potential of Quercetin Analogous: Prospective and Advances.}, journal = {Recent advances in food, nutrition & agriculture}, volume = {}, number = {}, pages = {}, doi = {10.2174/012772574X332803240930065210}, pmid = {39513316}, issn = {2772-5758}, abstract = {The purpose of the article is to investigate the therapeutic potential of quer-cetin and related compounds by elucidating their pharmacological characteristics and molecular mechanisms of action. The potential benefits of quercetin and its analogs for cardiovascular health, disorders of the brain, metabolic disorders, and more are discussed in the discussion part of this page. Concerns about their clinical efficacy due to issues with bioavailability and distribution are also discussed. This region of the paper emphasizes the importance of researchers and clinicians working together to maximize the incorporation of these chemicals into real-world therapeutic approaches. In conclusion, quercetin, along with related substances, shows great potential in a wide range of therapeutic settings. Potentially useful for the management of a wide variety of illnesses, their multiple methods of action include the regulation of pathways for cell signaling and interaction with different enzymes. However, additional clinical tri-als are needed to verify their efficacy and safety.}, } @article {pmid39512134, year = {2025}, author = {Pattee, GL}, title = {Gastrostomy in Amyotrophic Lateral Sclerosis: Timing Enhances Survival.}, journal = {Muscle & nerve}, volume = {71}, number = {1}, pages = {3-5}, doi = {10.1002/mus.28294}, pmid = {39512134}, issn = {1097-4598}, } @article {pmid39512085, year = {2025}, author = {White, CG and Hancewicz, TM and Fasasi, A and Wright, J and Lavine, BK}, title = {Alternating and Modified Alternating Least Squares Applied to Raman Spectra of Finished Gasolines.}, journal = {Applied spectroscopy}, volume = {79}, number = {5}, pages = {808-815}, doi = {10.1177/00037028241292649}, pmid = {39512085}, issn = {1943-3530}, abstract = {Extraction of components from individual refinery streams (e.g., reformates and alkylates) in finished gasoline was undertaken using Raman spectroscopy to characterize the chemical content of the finished product. Modified alternating least squares (MALS) was used for separating Raman spectroscopic data sets of the finished product into its pure individual components. The advantages of MALS over alternating least squares (ALS) for multicomponent resolution are highlighted in this study using three Raman spectroscopic data sets which provide a suitable benchmark for comparing the performance of these two methods. MALS is superior to ALS in terms of accuracy and can better resolve components than ALS, and it is also more robust toward collinear data. Finally, components near the noise level usually cannot be extracted by ALS because of instability when inverting the covariance structure which inflates the noise present in the data. However, these same components can be extracted by MALS due to the stabilization of the least squares regression with respect to the matrix inversion using modified techniques from ridge regression.}, } @article {pmid39511965, year = {2025}, author = {Bhai, S and Levine, T and Moore, D and Bowser, R and Heim, AJ and Walsh, M and Shibani, A and Simmons, Z and Grogan, J and Goyal, NA and Govindarajan, R and Hussain, Y and Papsdorf, T and Schwasinger-Schmidt, T and Olney, N and Goslin, K and Pulley, M and Kasarskis, E and Weiss, M and Katz, SW and Moser, S and Jabari, D and Jawdat, O and Statland, J and Dimachkie, MM and Barohn, R and , }, title = {A 40-week phase 2B randomized, multicenter, double-blind, placebo-controlled study evaluating the safety and efficacy of memantine in amyotrophic lateral sclerosis.}, journal = {Muscle & nerve}, volume = {71}, number = {1}, pages = {63-72}, pmid = {39511965}, issn = {1097-4598}, support = {R01 FD003937/FD/FDA HHS/United States ; R01FD003937//FDA-OPD/ ; //U.S. Food and Drug Administration/ ; }, mesh = {Humans ; *Memantine/therapeutic use ; *Amyotrophic Lateral Sclerosis/drug therapy ; Male ; Female ; Double-Blind Method ; Middle Aged ; Aged ; Adult ; Aged, 80 and over ; *Disease Progression ; Treatment Outcome ; Young Adult ; Excitatory Amino Acid Antagonists/therapeutic use ; }, abstract = {INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative disease with no known cure, limited treatment options with minimal benefits, and significant unmet need for disease modifying therapies.

AIMS: This study investigated memantine's impact on ALS progression, with an additional focus on the effects of memantine on cognitive and behavioral changes associated with the disease.

METHODS: A randomized, double-blind, placebo-controlled clinical trial was conducted from December 2018 to September 2020. ALS patients were enrolled in-person and remotely across 13 sites in the United States. Participants were randomized to memantine (20 mg twice daily) or placebo in a 2:1 ratio and completed 36 weeks of treatment. The primary outcome of disease progression was assessed by the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R), and blood was collected for biomarker analysis.

RESULTS: Of the 99 participants enrolled in the study, 89 were randomized to memantine or placebo (ages 24-83 years, male-to-female ratio ~3:2). Fifty-two participants completed the study treatment with no significant differences in disease progression, biomarker changes (including neurofilament light chain [NfL]), or neuropsychiatric testing noted between the groups. Initial NfL values correlated with the rate of ALSFRS-R decline.

DISCUSSION: In this study, memantine did not impact ALS disease progression or neuropsychiatric symptoms. Trials with remote enrollment may help trial participation and success.}, } @article {pmid39511939, year = {2025}, author = {Eisen, A and Vucic, S and Kiernan, MC}, title = {Amyotrophic lateral sclerosis represents corticomotoneuronal system failure.}, journal = {Muscle & nerve}, volume = {71}, number = {4}, pages = {499-511}, pmid = {39511939}, issn = {1097-4598}, mesh = {*Amyotrophic Lateral Sclerosis/pathology/physiopathology ; Humans ; Animals ; *Motor Neurons/pathology/physiology ; *Motor Cortex/pathology/physiopathology ; }, abstract = {Several decades have passed since the anterograde corticomotoneuronal hypothesis for amyotrophic lateral sclerosis (ALS) was proposed. The intervening years have witnessed its emergent support based on anatomical, pathological, physiological, neuroimaging, and molecular biological studies. The evolution of an extensive corticomotoneuronal system appears restricted to the human species, with ALS representing a uniquely human disease. While some, very select non-human primates have limited corticomotoneuronal projections, these tend to be absent in all other animals. From a general perspective, the early clinical features of ALS may be considered to reflect failure of the corticomotoneuronal system. The characteristic loss of skilled motor dexterity involving the limbs, and speech impairment through progressive bulbar dysfunction specifically involve those motor units having the strongest corticomotoneuronal projections. A similar explanation likely underlies the unique "split phenotypes" that have now been well characterized in ALS. Large Betz cells and other pyramidal corticomotoneuronal projecting neurons, with their extensive dendritic arborization, are particularly vulnerable to the elements of the ALS exposome such as aging, environmental stress and lifestyle changes. Progressive failure of the proteosome impairs nucleocytoplasmic shuffling and induces toxic but soluble TDP-43 to aggregate in corticomotoneurons. Betz cell failure is further accentuated through dysfunction of its profuse dendritic arborizations. Clarification of system specific genomes and neural networks will likely promote the initiation of precision medicine approaches directed to support the key structure that underlies the neurological manifestations of ALS, the corticomotoneuronal system.}, } @article {pmid39511821, year = {2025}, author = {Grady, A and Lorch, R and Giles, L and Lamont, H and Anderson, A and Pearson, N and Romiti, M and Lum, M and Stuart, A and Leigh, L and Yoong, SL}, title = {The impact of early childhood education and care-based interventions on child physical activity, anthropometrics, fundamental movement skills, cognitive functioning, and social-emotional wellbeing: A systematic review and meta-analysis.}, journal = {Obesity reviews : an official journal of the International Association for the Study of Obesity}, volume = {26}, number = {2}, pages = {e13852}, pmid = {39511821}, issn = {1467-789X}, support = {APP1170042//National Health and Medical Research Council/ ; Heart Foundation Postdoctoral Fellowship 102518//National Heart Foundation of Australia/ ; Heart Foundation Future Leader Fellowship 106654//National Heart Foundation of Australia/ ; }, mesh = {Humans ; *Cognition ; Child, Preschool ; *Exercise/psychology ; Child ; Infant ; Motor Skills/physiology ; Pediatric Obesity/psychology/prevention & control ; Anthropometry ; Early Intervention, Educational ; }, abstract = {This review assessed the effectiveness of ECEC-based interventions to improve child physical activity, and intervention impact on child weight-based anthropometrics, fundamental movement skills (FMS), cognitive functioning, and social-emotional wellbeing. Adverse effects and costs were assessed. Finch et al's 2014 systematic review was updated. Electronic databases were searched 10 September 2014 to 27 October 2022. Included studies were randomized controlled trials of ECEC interventions targeting physical activity among children aged 0-6 years. The methodological quality of studies was assessed using Cochrane's Risk of Bias tool v2. Standardized mean differences (SMD) were calculated for each outcome with meta-analysis undertaken; otherwise, findings were described narratively. Fifty-three studies were included. ECEC-based interventions were found to significantly improve child physical activity (SMD 0.193, 95% confidence interval [CI] 0.09 to 0.3; p < 0.001) and FMS (SMD 0.544, 95% CI 0.1 to 0.98; p = 0.015), compared to control. Small positive, but non-significant, effects were found for weight-based anthropometrics, cognitive functioning, and social-emotional wellbeing. Few studies reported adverse effects (n = 10), and no studies reported formal economic analyses. While ECEC-based interventions can significantly improve child physical activity and FMS, further evidence of their impact on cognitive functioning, social-emotional wellbeing, and the cost-effectiveness of such interventions is required to inform policy and practice.}, } @article {pmid39511709, year = {2025}, author = {Fontaine, M and Horowitz, K and Anoja, N and Genge, A and Salmon, K}, title = {How the prospect of a clinical trial impacts decision-making for predictive genetic testing in ALS.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {26}, number = {3-4}, pages = {343-351}, doi = {10.1080/21678421.2024.2423718}, pmid = {39511709}, issn = {2167-9223}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/diagnosis/psychology ; *Genetic Testing/methods ; Male ; Female ; Middle Aged ; *Decision Making ; Adult ; Aged ; Genetic Counseling/psychology ; *Clinical Trials as Topic/psychology ; C9orf72 Protein/genetics ; Surveys and Questionnaires ; Genetic Predisposition to Disease ; Superoxide Dismutase-1/genetics ; }, abstract = {Objective: Genetic testing practices are rapidly evolving for people living with, or at-risk for, amyotrophic lateral sclerosis (ALS), due to emerging genotype-driven therapies. This study explored how individuals at-risk for familial ALS (fALS) perceive the opportunity to participate in a clinical trial, and to better understand how that may influence the decision-making process for predictive genetic testing. Methods: This study used both quantitative and qualitative data analyses. Data were collected through an online questionnaire, followed by semi-structured interviews conducted with twelve (n = 12) individuals at-risk for either SOD1- or C9orf72-ALS who had predictive testing prior to study participation. Interview data were analyzed using reflexive thematic analysis. Results: Three overarching themes were conceptualized from the data: i) the psychosocial impact of fALS; ii) perspectives of at-risk individuals on research involvement; and iii) predictive genetic counseling and testing considerations. These results contribute perspectives of the lived experience to inform predictive genetic counseling and testing practices for individuals at-risk for fALS. Conclusion: Individuals at-risk for fALS view potential participation in a presymptomatic clinical trial as an actionable measure that may increase their desire for predictive genetic testing. Genetic counseling was identified as a critical component of the predictive testing process given the life-changing implications associated with a positive result. Increased access to predictive genetic counseling, and in a timely manner, is a significant need in the ALS population given potential access to gene-specific therapies in the presymptomatic stage.}, } @article {pmid39511225, year = {2024}, author = {Silvestri, B and Mochi, M and Mawrie, D and de Turris, V and Colantoni, A and Borhy, B and Medici, M and Anderson, EN and Garone, MG and Zammerilla, CP and Simula, M and Ballarino, M and Pandey, UB and Rosa, A}, title = {HuD impairs neuromuscular junctions and induces apoptosis in human iPSC and Drosophila ALS models.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {9618}, pmid = {39511225}, issn = {2041-1723}, support = {CN00000041//Ministero dell'Istruzione, dell'Università e della Ricerca (Ministry of Education, University and Research)/ ; 2022BYB33L//Ministero dell'Istruzione, dell'Università e della Ricerca (Ministry of Education, University and Research)/ ; CN00000041//Ministero dell'Istruzione, dell'Università e della Ricerca (Ministry of Education, University and Research)/ ; RP123188EC9F2349//Sapienza Università di Roma (Sapienza University of Rome)/ ; RM12117A5DE7A45B//Sapienza Università di Roma (Sapienza University of Rome)/ ; LT0024/2022-L//Human Frontier Science Program (HFSP)/ ; R01 NS081303/NS/NINDS NIH HHS/United States ; }, mesh = {Humans ; *Neuromuscular Junction/metabolism ; *Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology ; Animals ; *Apoptosis/genetics ; *Induced Pluripotent Stem Cells/metabolism ; *Motor Neurons/metabolism/pathology ; *RNA-Binding Protein FUS/metabolism/genetics ; *Disease Models, Animal ; *ELAV-Like Protein 4/metabolism/genetics ; Mutation ; Oxidative Stress ; Drosophila Proteins/metabolism/genetics ; Drosophila melanogaster/genetics ; Female ; Male ; Drosophila ; }, abstract = {Defects at the neuromuscular junction (NMJ) are among the earliest hallmarks of amyotrophic lateral sclerosis (ALS). According to the "dying-back" hypothesis, NMJ disruption not only precedes but also triggers the subsequent degeneration of motoneurons in both sporadic (sALS) and familial (fALS) ALS. Using human induced pluripotent stem cells (iPSCs), we show that the RNA-binding protein HuD (ELAVL4) contributes to NMJ defects and apoptosis in FUS-ALS. HuD overexpression mimics the severe FUS[P525L] mutation, while its knockdown rescues the FUS[P525L] phenotypes. In Drosophila, neuronal overexpression of the HuD ortholog, elav, induces motor dysfunction, and its knockdown improves motor function in a FUS-ALS model. Finally, we report increased HuD levels upon oxidative stress in human motoneurons and in sALS patients with an oxidative stress signature. Based on these findings, we propose that HuD plays a role downstream of FUS mutations in fALS and in sALS related to oxidative stress.}, } @article {pmid39510899, year = {2024}, author = {Kaul, M and Mukherjee, D and Weiner, HL and Cox, LM}, title = {Gut microbiota immune cross-talk in amyotrophic lateral sclerosis.}, journal = {Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics}, volume = {21}, number = {6}, pages = {e00469}, pmid = {39510899}, issn = {1878-7479}, support = {P51 OD011133/OD/NIH HHS/United States ; R01 NS115951/NS/NINDS NIH HHS/United States ; R21 NS126866/NS/NINDS NIH HHS/United States ; }, mesh = {*Amyotrophic Lateral Sclerosis/immunology/microbiology ; *Gastrointestinal Microbiome/immunology/physiology ; Humans ; Animals ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by the loss of motor neurons. While there has been significant progress in defining the genetic contributions to ALS, greater than 90 % of cases are sporadic, which suggests an environmental component. The gut microbiota is altered in ALS and is an ecological factor that contributes to disease by modulating immunologic, metabolic, and neuronal signaling. Depleting the microbiome worsens disease in the SOD1 ALS animal model, while it ameliorates disease in the C9orf72 model of ALS, indicating critical subtype-specific interactions. Furthermore, administering beneficial microbiota or microbial metabolites can slow disease progression in animal models. This review discusses the current state of microbiome research in ALS, including interactions with different ALS subtypes, evidence in animal models and human studies, key immunologic and metabolomic mediators, and a path toward microbiome-based therapies for ALS.}, } @article {pmid39510439, year = {2024}, author = {Tan, X and Su, X and Wang, Y and Liang, W and Wang, D and Huo, D and Wang, H and Qi, Y and Zhang, W and Han, L and Zhang, D and Wang, M and Xu, J and Feng, H}, title = {BRD7 regulates cellular senescence and apoptosis in ALS by modulating p21 expression and p53 mitochondrial translocation respectively.}, journal = {Neuroscience}, volume = {563}, number = {}, pages = {51-62}, doi = {10.1016/j.neuroscience.2024.11.004}, pmid = {39510439}, issn = {1873-7544}, mesh = {*Cellular Senescence/physiology ; *Apoptosis/physiology ; *Tumor Suppressor Protein p53/metabolism/genetics ; Humans ; *Cyclin-Dependent Kinase Inhibitor p21/metabolism/genetics ; *Mitochondria/metabolism ; *Amyotrophic Lateral Sclerosis/metabolism/pathology/genetics ; *Motor Neurons/metabolism/pathology ; Chromosomal Proteins, Non-Histone/metabolism/genetics ; Male ; Female ; Middle Aged ; Aged ; Bromodomain Containing Proteins ; }, abstract = {Cellular senescence is involved in the progression of neurodegenerative diseases. Motor neurons exhibit senescence-like alterations in ALS. BRD7, identified as a regulatory factor associated with cellular senescence, its function in ALS remains unclear. This study aims to investigate the potential role and mechanisms of BRD7 in ALS. We analyzed RNA levels using qRT-PCR, protein levels through immunofluorescence and western blot, and apoptosis via TUNEL staining. Cell transfection was conducted for in vitro experiments. The level of β-galactosidase was measured by β-galactosidase activity detection kit. ALS motor neurons exhibited senescence-like alterations, characterized by increased activity of p53, p21, and β-galactosidase, as well as reduced lamin B1 staining. Additionally, the expression of BRD7 was upregulated and induced cellular senescence and apoptosis. Downregulation of BRD7 alleviates the cellular senescence by inhibiting p21 rather than p53. Knockdown of BRD7 inhibited p53 mitochondrial translocation, leading to reduced apoptosis. Our results suggest that BRD7 plays an important role in the survival of ALS motor neurons. BRD7 knockdown can reduce cellular senescence and apoptosis by inhibiting p21 and p53 mitochondrial translocation.}, } @article {pmid39509425, year = {2024}, author = {Deng, YC and Liu, JW and Ting, HC and Kuo, TC and Chiang, CH and Lin, EY and Harn, HJ and Lin, SZ and Chang, CY and Chiou, TW}, title = {n-Butylidenephthalide recovered calcium homeostasis to ameliorate neurodegeneration of motor neurons derived from amyotrophic lateral sclerosis iPSCs.}, journal = {PloS one}, volume = {19}, number = {11}, pages = {e0311573}, pmid = {39509425}, issn = {1932-6203}, mesh = {*Amyotrophic Lateral Sclerosis/drug therapy/metabolism/pathology/genetics ; *Induced Pluripotent Stem Cells/metabolism/drug effects ; Humans ; *Motor Neurons/drug effects/metabolism/pathology ; *Calcium/metabolism ; *Homeostasis/drug effects ; *Superoxide Dismutase-1/genetics/metabolism ; *Phthalic Anhydrides/pharmacology ; Cell Differentiation/drug effects ; Mutation ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease that causes muscle atrophy and primarily targets motor neurons (MNs). Approximately 20% of familial ALS cases are caused by gain-of-function mutations in superoxide dismutase 1 (SOD1), leading to MN degeneration and ion channel dysfunction. Previous studies have shown that n-Butylidenephthalide (BP) delays disease progression and prolongs survival in animal models of ALS. However, no studies have been conducted on models from human sources. Herein, we examined the protective efficacy of BP on MNs derived from induced pluripotent stem cells (iPSCs) of an ALS patient harboring the SOD1G85R mutation as well as on those derived from genetically corrected iPSCs (SOD1G85G). Our results demonstrated that the motor neurons differentiated from iPSC with SOD1G85R mutation exhibited characteristics of neuron degeneration (as indicated by the reduction of neurofilament expression) and ion channel dysfunction (in response to potassium chloride (KCl) and L-glutamate stimulation), in contrast to those derived from the gene corrected iPSC (SOD1G85G). Meanwhile, BP treatment effectively restored calcium ion channel function by reducing the expression of glutamate receptors including glutamate ionotropic receptor AMPA type subunit 3 (GluR3) and glutamate ionotropic receptor NMDA type subunit 1 (NMDAR1). Additionally, BP treatment activated autophagic pathway to attenuate neuron degeneration. Overall, this study supports the therapeutic effects of BP on ALS patient-derived neuron cells, and suggests that BP may be a promising candidate for future drug development.}, } @article {pmid39508675, year = {2024}, author = {}, title = {DSP-01 conversion from PLS to ALS: a Dutch cohort study.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {25}, number = {sup1}, pages = {262-279}, doi = {10.1080/21678421.2024.2403307}, pmid = {39508675}, issn = {2167-9223}, } @article {pmid39508663, year = {2024}, author = {}, title = {Platform Communications: Abstract Book 35th International Symposium on ALS/MND (Complete printable file).}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {25}, number = {sup1}, pages = {1-92}, doi = {10.1080/21678421.2024.2403293}, pmid = {39508663}, issn = {2167-9223}, } @article {pmid39508354, year = {2025}, author = {Bhatele, P and Pai, AR}, title = {Wine Glass Sign in Bulbar Onset Amyotrophic Lateral Sclerosis.}, journal = {Annals of neurology}, volume = {97}, number = {3}, pages = {558-560}, doi = {10.1002/ana.27131}, pmid = {39508354}, issn = {1531-8249}, } @article {pmid39506867, year = {2024}, author = {Ishihara, T and Koyama, A and Atsuta, N and Tada, M and Toyoda, S and Kashiwagi, K and Hirokawa, S and Hatano, Y and Yokoseki, A and Nakamura, R and Tohnai, G and Izumi, Y and Kaji, R and Morita, M and Tamura, A and Kano, O and Aoki, M and Kuwabara, S and Kakita, A and Sobue, G and Onodera, O}, title = {SMN2 gene copy number affects the incidence and prognosis of motor neuron diseases in Japan.}, journal = {BMC medical genomics}, volume = {17}, number = {1}, pages = {263}, pmid = {39506867}, issn = {1755-8794}, support = {17K09750//Scientific Research from the Japan Society for the Promotion of Science/ ; 21K07272//Scientific Research from the Japan Society for the Promotion of Science/ ; 17ek0109284h0001//Japan Agency for Medical Research and Development/ ; 17ek0109284h0001//Japan Agency for Medical Research and Development/ ; 17ek0109284h0001//Japan Agency for Medical Research and Development/ ; 26117006//Scientific Research on Innovative Areas from MEXT/ ; JPMH23FC1008//MHLW Research on rare and intractable diseases Program/ ; }, mesh = {Humans ; *Survival of Motor Neuron 2 Protein/genetics ; Male ; Japan/epidemiology ; Middle Aged ; Female ; Prognosis ; *Motor Neuron Disease/genetics ; *Gene Dosage ; Incidence ; Amyotrophic Lateral Sclerosis/genetics ; Aged ; Adult ; Case-Control Studies ; DNA Copy Number Variations ; }, abstract = {BACKGROUND: The copy number status (CNS) of the survival motor neuron (SMN) gene may influence the risk and prognosis of amyotrophic lateral sclerosis (ALS) and lower motor neuron diseases (LMND) other than spinal muscular atrophy (SMA). However, previous studies of this association, mainly from Europe, have yielded controversial results, suggesting possible regional differences. Here, we investigated the effect of the SMN gene in Japanese patients with ALS and LMND.

METHODS: We examined the SMN copy numbers and clinical histories of 487 Japanese patients with sporadic ALS (281 men; mean age at onset 61.5 years), 50 with adult LMND (50 men; mean age at onset 58.4 years) and 399 Japanese controls (171 men; mean age 62.2 years). Patients with pathogenic mutations in ALS-causing genes were excluded. SMN1 and SMN2 copy numbers were determined using the droplet digital polymerase chain reaction.

RESULTS: The frequency of a copy number of one for the SMN2 gene was higher in patients with ALS (38.0%) than in healthy controls (30.8%) (odds ratio (OR) = 1.37, 95% confidence interval (CI) = 1.04-1.82, p < 0.05). The SMN2 copy number affected the survival time of patients with ALS (median time: 0 copies, 34 months; 1 copy, 39 months; 2 copies, 44 months; 3 copies, 54 months; log-rank test, p < 0.05). Cox regression analysis revealed that the SMN2 copy number was associated with increased mortality (hazard ratio = 0.84, 95% CI = 0.72-0.98, p < 0.05). Also, null SMN2 cases were significantly more frequent in the LMND group (12.0%) than in the control group (4.8%) (OR = 2.73, 95% CI = 1.06-6.98, p < 0.05).

CONCLUSIONS: Our findings suggest that SMN2 copy number reduction may adversely affect the onset and prognosis of MND, including ALS and LMND, in Japanese.}, } @article {pmid39506789, year = {2024}, author = {Niccolai, E and Di Gloria, L and Trolese, MC and Fabbrizio, P and Baldi, S and Nannini, G and Margotta, C and Nastasi, C and Ramazzotti, M and Bartolucci, G and Bendotti, C and Nardo, G and Amedei, A}, title = {Host genetics and gut microbiota influence lipid metabolism and inflammation: potential implications for ALS pathophysiology in SOD1[G93A] mice.}, journal = {Acta neuropathologica communications}, volume = {12}, number = {1}, pages = {174}, pmid = {39506789}, issn = {2051-5960}, support = {SG-2019-12371083//Italian Ministry of Health/ ; PE0000006//Ministero dell'Istruzione, dell'Università e della Ricerca/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/physiology ; *Amyotrophic Lateral Sclerosis/genetics/metabolism/microbiology/pathology ; Mice ; *Mice, Transgenic ; *Lipid Metabolism/genetics ; Inflammation/metabolism/pathology ; Mice, Inbred C57BL ; Superoxide Dismutase-1/genetics/metabolism ; Disease Models, Animal ; }, abstract = {Amyotrophic Lateral Sclerosis (ALS) is a devastating neurodegenerative disorder characterized by the progressive loss of motor neurons, with genetic and environmental factors contributing to its complex pathogenesis. Dysregulated immune responses and altered energetic metabolism are key features, with emerging evidence implicating the gut microbiota (GM) in disease progression. We investigated the interplay among genetic background, GM composition, metabolism, and immune response in two distinct ALS mouse models: 129Sv_G93A and C57Ola_G93A, representing rapid and slow disease progression, respectively.Using 16 S rRNA sequencing and fecal metabolite analysis, we characterized the GM composition and metabolite profiles in non-transgenic (Ntg) and SOD1[G93A] mutant mice of both strains. Our results revealed strain-specific differences in GM composition and functions, particularly in the abundance of taxa belonging to Erysipelotrichaceae and the levels of short and medium-chain fatty acids in fecal samples. The SOD1 mutation induces significant shifts in GM colonization in both strains, with C57Ola_G93A mice showing changes resembling those in 129 Sv mice, potentially affecting disease pathogenesis. ALS symptom progression does not significantly alter microbiota composition, suggesting stability.Additionally, we assessed systemic immunity and inflammatory responses revealing strain-specific differences in immune cell populations and cytokine levels.Our findings underscore the substantial influence of genetic background on GM composition, metabolism, and immune response in ALS mouse models. These strain-specific variations may contribute to differences in disease susceptibility and progression rates. Further elucidating the mechanisms underlying these interactions could offer novel insights into ALS pathogenesis and potential therapeutic targets.}, } @article {pmid39508106, year = {2024}, author = {Gao, XF and Chen, AQ and Tang, HY and Kong, XQ and Zhang, H and Wang, ZM and Lu, W and Wang, LG and Wang, F and Zhou, WY and Gu, Y and Zuo, GF and Ge, Z and Zhang, JJ and Chen, SL}, title = {m[6]A Modification of Profilin-1 in Vascular Smooth Muscle Cells Drives Phenotype Switching and Neointimal Hyperplasia via Activation of the p-ANXA2/STAT3 Pathway.}, journal = {Arteriosclerosis, thrombosis, and vascular biology}, volume = {44}, number = {12}, pages = {2543-2559}, pmid = {39508106}, issn = {1524-4636}, mesh = {Animals ; *Neointima ; *Muscle, Smooth, Vascular/metabolism/pathology ; *Hyperplasia ; *Phenotype ; *STAT3 Transcription Factor/metabolism/genetics ; *Myocytes, Smooth Muscle/metabolism/pathology ; *Signal Transduction ; *Disease Models, Animal ; *Proto-Oncogene Mas ; Male ; *Profilins/metabolism/genetics ; *Mice, Knockout ; *Adenosine/metabolism/analogs & derivatives ; Humans ; Mice ; Mice, Inbred C57BL ; Rats ; Cells, Cultured ; Rats, Sprague-Dawley ; Phosphorylation ; Coronary Restenosis/metabolism/pathology/genetics/etiology ; Carotid Stenosis/metabolism/pathology/genetics ; Cell Proliferation ; }, abstract = {BACKGROUND: In-stent restenosis is characterized by a significant reduction in lumen diameter within the stented segment, primarily attributed to excessive proliferation of vascular smooth muscle cells (VSMCs) and neointimal hyperplasia. PFN1 (profilin-1), an actin-sequestering protein extensively studied in amyotrophic lateral sclerosis, remains less explored in neointimal hyperplasia.

METHODS: Utilizing single-cell RNA sequencing alongside data from in-stent restenosis patients and various experimental in-stent restenosis models (swine, rats, and mice), we investigated the role of PFN1 in promoting VSMC phenotype switching and neointimal hyperplasia.

RESULTS: Single-cell RNA sequencing of stenotic rat carotid arteries revealed a critical role for PFN1 in neointimal hyperplasia, a finding corroborated in stented swine coronary arteries, in-stent restenosis patients, PFN1[SMC-IKO] (SMC-specific PFN1 knockout) mice, and PFN1 overexpressed mice. PFN1 deletion was shown to suppress VSMC phenotype switching and neointimal hyperplasia in PFN1[SMC-IKO] mice subjected to a wire-injured model. To elucidate the observed discordance in PFN1 mRNA and protein levels, we identified that METTL3 (N[6]-methyladenosine methyltransferase) and YTHDF3 (YTH N6-methyladenosine RNA binding protein F3; N[6]-methyladenosine-specific reader) enhance PFN1 translation efficiency in an N[6]-methyladenosine-dependent manner, confirmed through experiments involving METTL3 knockout and YTHDF3 knockout mice. Furthermore, PFN1 was mechanistically found to interact with the phosphorylation of ANXA2 (annexin A2) by recruiting Src (SRC proto-oncogene, nonreceptor tyrosine kinase), promoting the phosphorylation of STAT3 (signal transducer and activator of transcription 3), a typical transcription factor known to induce VSMC phenotype switching.

CONCLUSIONS: This study unveils the significance of PFN1 N[6]-methyladenosine modification in VSMCs, demonstrating its role in promoting phenotype switching and neointimal hyperplasia through the activation of the p-ANXA2 (phospho-ANXA2)/STAT3 pathway.}, } @article {pmid39505881, year = {2024}, author = {Li, J and Jaiswal, MK and Chien, JF and Kozlenkov, A and Jung, J and Zhou, P and Gardashli, M and Pregent, LJ and Engelberg-Cook, E and Dickson, DW and Belzil, VV and Mukamel, EA and Dracheva, S}, title = {Author Correction: Divergent single cell transcriptome and epigenome alterations in ALS and FTD patients with C9orf72 mutation.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {9588}, doi = {10.1038/s41467-024-53972-1}, pmid = {39505881}, issn = {2041-1723}, } @article {pmid39505319, year = {2024}, author = {Lee, J and Kim, A and Choi, SJ and Cho, E and Seo, J and Oh, SI and Jung, J and Kim, JS and Sung, JJ and Abrahams, S and Hong, YH}, title = {Erratum: Development and Validation of the Korean Version of the Edinburgh Cognitive and Behavioral Amyotrophic Lateral Sclerosis Screen (ECAS-K).}, journal = {Journal of clinical neurology (Seoul, Korea)}, volume = {20}, number = {6}, pages = {637}, doi = {10.3988/jcn.2022.0403e}, pmid = {39505319}, issn = {1738-6586}, abstract = {This corrects the article on p. 454 in vol. 19, PMID: 37488957.}, } @article {pmid39505137, year = {2024}, author = {Abbasi, H and Jourabchi-Ghadim, N and Asgarzade, A and Mirshekari, M and Ebrahimi-Mameghani, M}, title = {Unveiling the veil of adipokines: A meta-analysis and systematic review in amyotrophic lateral sclerosis.}, journal = {Neuroscience}, volume = {563}, number = {}, pages = {1-9}, doi = {10.1016/j.neuroscience.2024.11.003}, pmid = {39505137}, issn = {1873-7544}, mesh = {*Amyotrophic Lateral Sclerosis/blood/metabolism ; Humans ; *Adipokines/blood ; Ghrelin/blood ; Leptin/blood ; Adiponectin/blood ; Disease Progression ; }, abstract = {BACKGROUND: Adipokines are proposed to be associated with ALS progression through assorted pathways. Therefore, The present meta-analysis explored the link between various adipokines and ALS progression.

METHOD: International database like PubMed, Scopus, and Web of Science databases were searched to achieve eligible papers published before December 2023. The following PICO structure was utilized: Population (patients with ALS); Intervention (serum concentrations of ghrelin, leptin, and adiponectin), Comparison (with or without controls), and Outcome (ALS progression). the risk of bias of selected papers was assessed through the Newcastle-Ottawa Scale (NOS) tool.

RESULTS: 11 out of 240 papers were selected for this study which were published between 2010 and 2024. Lower serum leptin concentrations were detected in the ALS compared to control groups (WMD: -0.91, 95% CI:-1.77, -0.05). Serum concentrations of adiponectin were higher in ALS compared to control groups (WMD: 0.41, 95% CI:-0.7, 0.89). Ultimately, The serum concentrations of ghrelin in the ALS groups were lower than control groups (WMD: -1.21, 95% CI: -2.95, 0.53).

CONCLUSION: Our findings revealed that serum concentrations of ghrelin and leptin were higher in ALS patients compared to control, unlike adiponectin.}, } @article {pmid39503426, year = {2025}, author = {Shimizu, M and Okuno, T}, title = {Disruption of neuronal actin barrier promotes the entry of disease-implicated proteins to exacerbate amyotrophic lateral sclerosis pathology.}, journal = {Neural regeneration research}, volume = {20}, number = {9}, pages = {2589-2590}, pmid = {39503426}, issn = {1673-5374}, } @article {pmid39503423, year = {2025}, author = {Alfahel, L and Rajkovic, A and Israelson, A}, title = {Translational challenges in amyotrophic lateral sclerosis therapy with macrophage migration inhibitory factor.}, journal = {Neural regeneration research}, volume = {20}, number = {9}, pages = {2583-2584}, pmid = {39503423}, issn = {1673-5374}, } @article {pmid39503319, year = {2024}, author = {Bedlack, R and Li, X and Evangelista, BA and Panzetta, ME and Kwan, J and Gittings, LM and Sattler, R}, title = {The Scientific and Therapeutic Rationale for Off-Label Treatments in Amyotrophic Lateral Sclerosis.}, journal = {Annals of neurology}, volume = {97}, number = {1}, pages = {15-27}, pmid = {39503319}, issn = {1531-8249}, support = {//ALS Association/ ; }, abstract = {There are no dramatically effective pharmacological treatments for most patients with amyotrophic lateral sclerosis, a complex disease with multiple underlying mechanisms, such as neuroinflammation, oxidative stress, mitochondrial dysfunction, microbiome alteration, and antiretroviral activity. We sifted through 15 years of reviews by a group called ALSUntangled to identify 8 alternative and off-label treatments that target ≥1 of these mechanisms, and have ≥1 human trial suggesting meaningful benefits. Given the overlapping pathological mechanisms of the highlighted products, we suggest that combinations of these treatments targeting diverse mechanisms might be worthwhile for future amyotrophic lateral sclerosis therapy development. ANN NEUROL 2024.}, } @article {pmid39503018, year = {2024}, author = {Rennie, O and Sharma, M and Helwa, N}, title = {Hepatobiliary anastomotic leakage: a narrative review of definitions, grading systems, and consequences of leaks.}, journal = {Translational gastroenterology and hepatology}, volume = {9}, number = {}, pages = {70}, pmid = {39503018}, issn = {2415-1289}, abstract = {BACKGROUND AND OBJECTIVE: Hepatobiliary diseases are a longstanding and significant medical challenge which, despite advances in surgical techniques, still carry risks for postoperative complications such as anastomotic leaks (ALs), which can include both postoperative pancreatic fistula (POPF) and bile leaks (BL). These complications incur significant human and economic costs on all those involved, including the patient, healthcare providers, and hospital systems. The aim of this study was to construct a narrative review of literature surrounding definitions and grading systems for ALs in the context of hepato-pancreato-biliary (HPB) procedures, and consequences of POPF and BL.

METHODS: A literature review was conducted by examining databases including PubMed, Web of Science, OVID Embase, Google Scholar, and Cochrane library databases. Searches were performed with the following search criteria: (((((((anastomosis) OR (anastomotic leak*)) OR (postoperative pancreatic fistula)) OR (bile leak*)) OR (pancreaticoduodenectomy)) OR (whipple)) AND ((hepatobiliary) OR (hepato-pancreato-biliary)) AND ((definition) OR (grading system*) OR (consequences) OR (outcomes) OR (risk factor*) OR (morbidity) OR (mortality))). Publications that were retrieved underwent further assessment to ensure other relevant publications were identified and included.

KEY CONTENT AND FINDINGS: A universally accepted definition and grading system for POPF and BL continues to be lacking, leading to variability in reported incidence in the literature. Various groups have worked to publish guidelines for defining and grading POPF and BL, with the International Study Group in Pancreatic Surgery (ISGPS) and International Study Group for Liver Surgery (ISGLS) definitions the current most recommended definitions for POPF and BL, respectively. The burden of AL on patients, healthcare providers, and hospitals is well documented in evidence from leak consequences, such as increased morbidity and mortality, higher reoperation rates, and increased readmission rates, among others.

CONCLUSIONS: AL remains a significant challenge in HPB surgery, despite medical advancements. Understanding the progress made in defining and grading leaks, as well as the range of negative outcomes that arise from AL, is crucial in improving patient care, reduce surgical mortality, and drive further advancements in earlier detection and treatment of AL.}, } @article {pmid39502740, year = {2024}, author = {Nishiyama, A and Niihori, T and Suzuki, N and Izumi, R and Akiyama, T and Kato, M and Funayama, R and Nakayama, K and Warita, H and Aoki, Y and Aoki, M}, title = {Updated Genetic Analysis of Japanese Familial ALS Patients Carrying SOD1 Variants Revealed Phenotypic Differences for Common Variants.}, journal = {Neurology. Genetics}, volume = {10}, number = {6}, pages = {e200196}, pmid = {39502740}, issn = {2376-7839}, abstract = {BACKGROUND AND OBJECTIVES: Amyotrophic lateral sclerosis (ALS) is an adult-onset progressive neurodegenerative disease. Approximately 10% of ALS cases are familial, and more than 20 causative genes have been identified. As we have previously reported, SOD1 variants are the most common causes of familial ALS in Japan. Because antisense oligonucleotides for SOD1-linked ALS are being used in practical applications, the types of variants and the clinical features of patients need to be updated.

METHODS: We consecutively recruited 160 families with familial ALS in Japan. We performed genetic analyses, focusing on SOD1-linked ALS as the most common in our cohort, updated their genotypes, and characterized clinical phenotypes.

RESULTS: A total of 26 SOD1 variants in 56 patients and 49 families (30.6%) were collected, with the 3 most common (p.His47Arg [the conventional numbering; H46R], p.Leu127Ser [L126S], p.Asn87Ser [N86S]) accounting for 38.8% of all families. We also identified 2 novel variants (p.Ile36Phe [I35F] and p.Asn132Argfs*3 [N131Rfs*3]). The mean age at onset was 48.9 ± 12.2 (mean ± SD) years for all patients with SOD1-linked ALS. Lower limb onset comprised 70% of cases. The mean disease duration was 64.7 ± 82 months, and the median survival was 71.5 months. Some variants led to a relatively homogeneous phenotype, although clinical characteristics differed among types of variants and families. Patients with p.His47Arg (H46R) showed slower progression with lower limb onset and a predominance of lower motor neuron involvement. The p.Leu127Ser (L126S) variant led to varying degrees of progression in heterozygous or homozygous states and presented incomplete penetrance. Intrafamilial phenotypic differences were observed in families carrying p.Asn87Ser (N86S). Four variants (p.Cys7Gly [C6G], p.His44Arg [H43R], p.Leu85Val [L84V], and p.Cys147Arg [C146R]) were found to be associated with rapid disease progression.

DISCUSSION: The genetic basis of familial ALS, at least for SOD1 variants, still differed by geographic and ethnic background. Understanding these clinical profiles will help optimize evaluation in targeted gene therapy worldwide and benefit efficient diagnosis, leading to precise application in clinical practice.}, } @article {pmid39501538, year = {2024}, author = {Bampton, A and McHutchison, C and Talbot, K and Benatar, M and Thompson, AG and Turner, MR}, title = {The Basis of Cognitive and Behavioral Dysfunction in Amyotrophic Lateral Sclerosis.}, journal = {Brain and behavior}, volume = {14}, number = {11}, pages = {e70115}, pmid = {39501538}, issn = {2162-3279}, support = {MR/T006927/1/MRC_/Medical Research Council/United Kingdom ; Thompson/Jan20/952-795//Motor Neurone Disease Association Lady Edith Wolfson Clinician Scientist Fellowship/ ; //Foulkes Foundation/ ; //National Institutes of Health (NIH)/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/physiopathology ; Humans ; Cognitive Dysfunction/etiology/physiopathology ; }, abstract = {OBJECTIVE: To summarize and evaluate evidence pertaining to the clinical, genetic, histopathological, and neuroimaging correlates of cognitive and behavioral dysfunction in amyotrophic lateral sclerosis (ALS).

METHODOLOGY: We comprehensively reviewed the literature on cognitive and behavioral manifestations of ALS, narrating findings from both cross-sectional and longitudinal studies. We discussed knowledge gaps in the evidence base and key limitations affecting studies to date, before formulating a framework for future research paradigms aimed at investigating clinicopathological correlates of neuropsychological dysfunction in ALS.

RESULTS: Studies have demonstrated clinical associations with cognitive dysfunction in ALS e.g., bulbar-onset of symptoms, pathological associations (extramotor TDP-43 deposition), and imaging associations (frontotemporal involvement). The most common behavioral deficit, apathy, is highly associated with verbal fluency, but longitudinal studies assessing behavioral dysfunction in ALS are comparatively lacking.

CONCLUSION: Longitudinal studies have been helpful in identifying several potential correlates of cognitive and behavioral dysfunction but have frequently been confounded by selection bias and inappropriate testing platforms. This review provides a framework for more robust assessment of clinicopathological associations of neuropsychological abnormalities in ALS in the future, advocating for greater utilization of pre-symptomatic C9orf72 repeat expansion-carrying cohorts.}, } @article {pmid39501102, year = {2025}, author = {Howard, J and Chaouch, A and Douglas, AGL and MacLeod, R and Roggenbuck, J and McNeill, A}, title = {Genetic testing for monogenic forms of motor neuron disease/amyotrophic lateral sclerosis in unaffected family members.}, journal = {European journal of human genetics : EJHG}, volume = {33}, number = {1}, pages = {7-13}, pmid = {39501102}, issn = {1476-5438}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/diagnosis ; *Family ; Genetic Counseling ; *Genetic Testing/methods/standards ; *Motor Neuron Disease/genetics/diagnosis ; }, abstract = {Motor neuron disease (MND), also referred to as amyotrophic lateral sclerosis (ALS), is a monogenic disease in a minority of cases, with autosomal dominant inheritance. Increasing numbers of people with MND are requesting genetic testing, and indeed receiving a genetic diagnosis. Consequently, requests for genetic counselling and predictive testing (i.e. of unaffected family members) are similarly expected to rise, alongside pre-symptomatic clinical trials. Despite this, there is no evidence-based guideline for predictive genetic testing in MND. This paper provides an overview of the genomic basis of MND, focusing specifically on the most common monogenic causes of MND. It then lays out the complexities of MND predictive testing, including the genetic landscape characterised by incomplete penetrance, clinical and genetic heterogeneity, and an oligogenic mechanism of pathogenesis in some cases. Additionally, there is limited research on the psychosocial impact of predictive genetic testing for MND, with studies suggesting potential difficulty in adjusting to the news, in part due to a lack of support and follow-up. This underscores a case for evidence-based, disease-specific guidance for predictive testing in MND.}, } @article {pmid39500920, year = {2024}, author = {Yu, M and Xu, J and Dutta, R and Trapp, B and Pieper, AA and Cheng, F}, title = {Network medicine informed multiomics integration identifies drug targets and repurposable medicines for Amyotrophic Lateral Sclerosis.}, journal = {NPJ systems biology and applications}, volume = {10}, number = {1}, pages = {128}, pmid = {39500920}, issn = {2056-7189}, support = {R21 AG083003/AG/NIA NIH HHS/United States ; R01 AG082118/AG/NIA NIH HHS/United States ; R56 AG074001/AG/NIA NIH HHS/United States ; RF1 AG082211/AG/NIA NIH HHS/United States ; R01 AG084250/AG/NIA NIH HHS/United States ; RF1 NS133812/NS/NINDS NIH HHS/United States ; RF1NS133812//U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; U01 AG073323/AG/NIA NIH HHS/United States ; U01AG073323//U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ ; R01AG082118//U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ ; R01AG066707//U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ ; R01 AG066707/AG/NIA NIH HHS/United States ; R01AG076448//U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ ; R21AG083003//U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ ; R01 AG076448/AG/NIA NIH HHS/United States ; RF1AG082211//U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ ; R01AG084250//U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/genetics/drug therapy/metabolism ; Humans ; *Quantitative Trait Loci/genetics ; Genome-Wide Association Study/methods ; Drug Repositioning/methods ; Genomics/methods ; Protein Interaction Maps/genetics/drug effects ; Multiomics ; }, abstract = {Amyotrophic Lateral Sclerosis (ALS) is a devastating, immensely complex neurodegenerative disease by lack of effective treatments. We developed a network medicine methodology via integrating human brain multi-omics data to prioritize drug targets and repurposable treatments for ALS. We leveraged non-coding ALS loci effects from genome-wide associated studies (GWAS) on human brain expression quantitative trait loci (QTL) (eQTL), protein QTL (pQTL), splicing QTL (sQTL), methylation QTL (meQTL), and histone acetylation QTL (haQTL). Using a network-based deep learning framework, we identified 105 putative ALS-associated genes enriched in known ALS pathobiological pathways. Applying network proximity analysis of predicted ALS-associated genes and drug-target networks under the human protein-protein interactome (PPI) model, we identified potential repurposable drugs (i.e., Diazoxide and Gefitinib) for ALS. Subsequent validation established preclinical evidence for top-prioritized drugs. In summary, we presented a network-based multi-omics framework to identify drug targets and repurposable treatments for ALS and other neurodegenerative disease if broadly applied.}, } @article {pmid39500483, year = {2024}, author = {Piotrkiewicz, M}, title = {Possible changes in motor neuron discharge characteristics in presymptomatic amyotrophic lateral sclerosis.}, journal = {The Journal of physiology}, volume = {602}, number = {24}, pages = {6631-6635}, doi = {10.1113/JP287788}, pmid = {39500483}, issn = {1469-7793}, } @article {pmid39496878, year = {2025}, author = {Yang, T and Wei, Q and Pang, D and Cheng, Y and Huang, J and Lin, J and Xiao, Y and Jiang, Q and Wang, S and Li, C and Shang, H}, title = {Mutation Screening of ATXN1, ATXN2, and ATXN3 in Amyotrophic Lateral Sclerosis.}, journal = {Molecular neurobiology}, volume = {62}, number = {4}, pages = {4854-4865}, pmid = {39496878}, issn = {1559-1182}, support = {82371430//National Natural Science Foundation of China/ ; 2022ZDZX0023//Sichuan Science and Technology Program/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics ; *Ataxin-1/genetics ; *Ataxin-3/genetics ; *Ataxin-2/genetics ; Male ; Female ; Middle Aged ; *Ataxins/genetics ; *Genetic Predisposition to Disease ; *Mutation/genetics ; DNA Mutational Analysis ; Aged ; *Genetic Testing ; Adult ; Repressor Proteins ; }, abstract = {Emerging evidence suggests potential disease modifying roles of ATXN1, ATXN2, and ATXN3 in amyotrophic lateral sclerosis (ALS). We aimed to provide a comprehensive variants profile of the ATXN1, ATXN2, and ATXN3 genes and examine the association of these variants with the risk and clinical characteristics of ALS. We screened and analyzed the rare variants in a cohort of 2220 ALS patients from Southwest China, using controls from the Genome Aggregation Database (gnomAD) and the China Metabolic Analytics Project (ChinaMAP). The over-representation of rare variants and their association with disease risk in ALS patients were assessed using Fisher's exact test with Bonferroni correction at both allele and gene levels. Kaplan-Meier analysis was employed to explore the relationship between the distribution of variants and survival. A total of 62 eligible rare missense variants were identified, comprising 32 from ATXN1, 21 from ATXN2, and 9 from ATXN3. Allelic association testing revealed a significant enrichment of the ATXN1 (c.2122C > G, p.Leu708Val) variant and the ATXN2 (c.3778C > G, p.Pro1260Ala) variant in ALS. Gene burden analysis indicated that variants in the ATXN1 and ATXN3 genes had a higher burden in ALS. Substantial heterogeneity in survival time was observed among patients carrying different variants within the same gene. However, there were no significant differences in survival between ALS patients grouped by N-terminal or C-terminal distribution. Our results provided a genetic variation profile of ATXN1, ATXN2, and ATXN3 in ALS patients, along with the clinical characteristics of individuals carrying these variations. This information might offer valuable insights for the ongoing ALS disease-modifying treatments.}, } @article {pmid39496465, year = {2024}, author = {Baker, MR and Maitland, S}, title = {Response to: 'Cortical Inexcitability in ALS: Correlating a Clinical Phenotype'.}, journal = {Journal of neurology, neurosurgery, and psychiatry}, volume = {}, number = {}, pages = {}, doi = {10.1136/jnnp-2024-334587}, pmid = {39496465}, issn = {1468-330X}, } @article {pmid39496035, year = {2024}, author = {Xu, W and Zhao, X and Wang, J and Guo, Y and Ren, Z and Cai, L and Wu, S and Zhou, M}, title = {Different intensities of physical activity for amyotrophic lateral sclerosis and Parkinson disease: A Mendelian randomization study and meta-analysis.}, journal = {Medicine}, volume = {103}, number = {44}, pages = {e40141}, pmid = {39496035}, issn = {1536-5964}, support = {ZYYLJRC201911//the Anhui Province Traditional Chinese Medicine Leading Talents Construction Project/ ; }, mesh = {Humans ; *Mendelian Randomization Analysis ; *Amyotrophic Lateral Sclerosis/genetics ; *Parkinson Disease/genetics/epidemiology ; *Exercise ; Genome-Wide Association Study ; }, abstract = {BACKGROUND: The causal relationships between amyotrophic lateral sclerosis (ALS), Parkinson disease and different intensities of physical activity (PA) are still inconclusive. To evaluate the causal impact of PA on ALS and Parkinson disease (PD), this study integrates evidence from Mendelian randomization (MR) using a meta-analysis approach.

METHODS: MR analyses on genetically predicted levels of PA (compose of self-reported moderate-to-vigorous physical activity [MVPA], self-reported vigorous physical activity [VPA], and strenuous sports or other exercises [SSOE]) regarding ALS and PD published up to July 27, 2024, were obtained from PubMed, Scopus, Web of Science, and Embase. De novo MR studies were analyzed utilizing publicly accessible datasets from genome-wide association studies and then meta-analyses were performed to pool the results.

RESULTS: Meta-analyses of results of 12 de novo MR studies analyses and 2 published MR studies indicated that genetic predicted levels of MVPA (odds ratio [OR]: 1.22, 95% confidence interval [CI]: 1.08-1.38), VPA (OR: 1.32, 95% CI: 1.08-1.60), and SSOE (OR: 1.35, 95% CI: 1.07-1.70) were related to a raised risk of ALS, but not causally with PD.

CONCLUSION: Our findings showed no causal relationships between MVPA, VPA, SSOE, and PD, while MVPA, VPA, and SSOE were associated with increased ALS risk, highlighting the need for targeted PA recommendations for disease management.}, } @article {pmid39495912, year = {2024}, author = {Wheeler, HB and Madrigal, AA and Chaim, IA}, title = {Mapping the future of oxidative RNA damage in neurodegeneration: Rethinking the status quo with new tools.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {121}, number = {46}, pages = {e2317860121}, pmid = {39495912}, issn = {1091-6490}, support = {R00 NS121511/NS/NINDS NIH HHS/United States ; 4R00NS121511-03//HHS | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; }, mesh = {Humans ; *Neurodegenerative Diseases/metabolism/genetics ; *RNA/metabolism/genetics ; *Oxidation-Reduction ; Oxidative Stress ; RNA-Binding Proteins/metabolism/genetics ; Proteomics/methods ; Animals ; }, abstract = {Over two decades ago, increased levels of RNA oxidation were reported in postmortem patients with ALS, Alzheimer's, Parkinson's, and other neurodegenerative diseases. Interestingly, not all cell types and transcripts were equally oxidized. Furthermore, it was shown that RNA oxidation is an early phenomenon, altogether indicating that oxidative RNA damage could be a driver, and not a consequence, of disease. Despite all these exciting observations, the field appears to have stagnated since then. We argue that this is a consequence of the shortcomings of technologies to model these diseases, limiting our understanding of which transcripts are being oxidized, which RNA-binding proteins are interacting with these RNAs, what their implications are in RNA processing, and as a result, what their potential role is in disease onset and progression. Here, we discuss the limits of previous technologies and propose ways by which advancements in iPSC-derived disease modeling, proteomics, and sequencing technologies can be combined and leveraged to answer new and decades-old questions.}, } @article {pmid39494889, year = {2024}, author = {Ito, SI and Tanaka, Y}, title = {Evaluation of LC3-II Release via Extracellular Vesicles in Relation to the Accumulation of Intracellular LC3-positive Vesicles.}, journal = {Journal of visualized experiments : JoVE}, volume = {}, number = {212}, pages = {}, doi = {10.3791/67385}, pmid = {39494889}, issn = {1940-087X}, mesh = {*Extracellular Vesicles/metabolism ; Humans ; *Microtubule-Associated Proteins/metabolism/genetics ; Autophagy/physiology ; DNA-Binding Proteins/metabolism/genetics ; }, abstract = {(Macro)autophagy represents a fundamental cellular degradation pathway. In this process, double-membraned vesicles known as autophagosomes engulf cytoplasmic contents, subsequently fusing with lysosomes for degradation. Beyond the canonical role, autophagy-related genes also modulate a secretory pathway involving the release of inflammatory molecules, tissue repair factors, and extracellular vesicles (EVs). Notably, the process of disseminating pathological proteins between cells, particularly in neurodegenerative diseases affecting the brain and spinal cord, underscores the significance of understanding this phenomenon. Recent research suggests that the transactive response DNA-binding protein 43 kDa (TDP-43), a key player in amyotrophic lateral sclerosis and frontotemporal lobar degeneration, is released in an autophagy-dependent manner via EVs enriched with the autophagosome marker microtubule-associated proteins 1A/1B light chain 3B-II (LC3-II), especially when autophagosome-lysosome fusion is inhibited. To elucidate the mechanism underlying the formation and release of LC3-II-positive EVs, it is imperative to establish an accessible and reproducible method for evaluating both intracellular and extracellular LC3-II-positive vesicles. This study presents a detailed protocol for assessing LC3-II levels via immunoblotting in cellular and EV fractions obtained through differential centrifugation. Bafilomycin A1 (Baf), an inhibitor of autophagosome-lysosome fusion, serves as a positive control to enhance the levels of intracellular and extracellular LC3-II-positive vesicles. Tumor susceptibility gene 101 (TSG101) is used as a marker for multivesicular bodies. Applying this protocol, it is demonstrated that siRNA-mediated knockdown of syntaxin-6 (STX6), a genetic risk factor for sporadic Creutzfeldt-Jakob disease, augments LC3-II levels in the EV fraction of cells treated with Baf while showing no significant effect on TSG101 levels. These findings suggest that STX6 may negatively regulate the extracellular release of LC3-II via EVs, particularly under conditions where autophagosome-lysosome fusion is impaired. Combined with established methods for evaluating autophagy, this protocol provides valuable insights into the role of specific molecules in the formation and release of LC3-II-positive EVs.}, } @article {pmid39494653, year = {2025}, author = {Springer, SA}, title = {Commentary on Gregory et al.: Fear of precipitated opioid withdrawal should not prevent buprenorphine initiation.}, journal = {Addiction (Abingdon, England)}, volume = {120}, number = {1}, pages = {21-22}, pmid = {39494653}, issn = {1360-0443}, support = {DP1 DA056106/DA/NIDA NIH HHS/United States ; NIDA DP1DA056106/DA/NIDA NIH HHS/United States ; }, abstract = {Provision of buprenorphine treatment for opioid use disorder is often stymied by clinicians’ concerns for precipitated opioid withdrawal. Gregory et al’s systematic review identified a low level of precipitated withdrawal with buprenorphine induction even among persons who reported fentanyl use. Evidence, not fear should guide treatment.}, } @article {pmid39494632, year = {2025}, author = {Uzunçakmak-Uyanık, H and Tan, E and Temuçin, ÇM and Yıldız, FG}, title = {Lack of habituation in somatosensory cortex but not in visual cortex of ALS patients.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {26}, number = {1-2}, pages = {93-102}, doi = {10.1080/21678421.2024.2421747}, pmid = {39494632}, issn = {2167-9223}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology ; Male ; Female ; Middle Aged ; *Somatosensory Cortex/physiopathology ; *Habituation, Psychophysiologic/physiology ; Aged ; *Evoked Potentials, Somatosensory/physiology ; *Visual Cortex/physiopathology ; *Evoked Potentials, Visual/physiology ; Adult ; Electroencephalography ; }, abstract = {OBJECTIVE: Amyotrophic lateral sclerosis (ALS) is a multisystem degenerative disease with extra-motor components. In ALS, there is also hyperexcitability of extra-motor areas. Habituation is defined as ''a response decrement" caused by repeated stimulations. Studies on evoked potential habituation can be conducted to detect cortical excitability. This study aimed to explore lack of habituation in non-motor cortical structures in ALS.

METHODS: Twenty-one ALS patients and 14 controls were enrolled. Recordings were obtained in 3 and 10 consecutive blocks (each containing 100 responses) during right median somatosensory evoked potential (SEP) and bilateral visual evoked potential (VEP), respectively. "Habituation" and "lack of habituation" were defined as the amount of increase or decrease in the average N20 or N75-P100 amplitude of the last blocks compared to the first blocks, respectively. Comparative analyses were performed between patient and control groups, as well as the first and last block within groups.

RESULTS: Paired sample t-test showed that in control group N20 peak amplitude of last blocks were significantly lower than first block values (p = 0.025) that indicate the physiological habituation as expected. On the other hand, there was not such a difference in ALS group (p = 0.239) which indicated lack of habituation.

CONCLUSIONS: Our study results suggest somatosensory hyperexcitability in line with cortical reorganization in ALS patients.}, } @article {pmid39494512, year = {2024}, author = {Donohoe, MN and Upadhyay, A and Pratt, DA}, title = {Ligand-Based Radical Reactivity of Metal Thiosemicarbazones Prompts the Identification of Platinum(II)-Based Cytoprotectants.}, journal = {Journal of the American Chemical Society}, volume = {146}, number = {45}, pages = {31307-31320}, doi = {10.1021/jacs.4c12713}, pmid = {39494512}, issn = {1520-5126}, mesh = {*Thiosemicarbazones/chemistry/pharmacology ; Ligands ; *Platinum/chemistry/pharmacology ; *Coordination Complexes/chemistry/pharmacology/chemical synthesis ; Humans ; Antioxidants/chemistry/pharmacology ; Lipid Peroxidation/drug effects ; Molecular Structure ; Copper/chemistry ; Neuroprotective Agents/chemistry/pharmacology/chemical synthesis ; }, abstract = {CuATSM, a copper(II) complex of a bis(thiosemicarbazone) of diacetyl, prevents oxidative cell death and acts as a neuroprotectant in vivo, prompting its evaluation to treat amyotrophic lateral sclerosis and other neurodegenerative conditions in the clinic. We recently demonstrated that CuATSM functions as a potent radical-trapping antioxidant (RTA), inhibiting lipid peroxidation and associated ferroptotic cell death by a noncanonical mechanism based on radical addition to the ligand backbone. Herein we report our investigations of the generality of this reactivity, which include studies of corresponding complexes of various other metals, including Co, Ru, Ni, Pd, Pt, and Au. Inhibited autoxidations of styrene and dioxane reveal that most of these complexes exhibit RTA activity, consistent with ligand-based reactivity, but the identity of the metal atom nevertheless plays a role. In particular, analyses of the electronic structures of the complexes of metals within the same group (i.e., the group 10 metals Ni, Pd and Pt) highlight how the metal atom can modulate the ligand-based reactivity by enabling spin delocalization to the other thiosemicarbazone moiety. The RTA activity determined in organic solution largely translates to phospholipid bilayers and mammalian cells, where most complexes inhibited lipid peroxidation and associated ferroptotic cell death. A preliminary structure-activity study revealed Pt complexes with potencies eclipsing those of archetype ferroptosis inhibitors ferrostatin-1 and liproxstatin-1, suggesting that Pt (and to a lesser extent Ni) bis(thiosemicarbazone)s may be better suited to optimization for therapeutic development than those based on Cu.}, } @article {pmid39494508, year = {2024}, author = {Mariani, D and Setti, A and Castagnetti, F and Vitiello, E and Stufera Mecarelli, L and Di Timoteo, G and Giuliani, A and D'Angelo, A and Santini, T and Perego, E and Zappone, S and Liessi, N and Armirotti, A and Vicidomini, G and Bozzoni, I}, title = {ALS-associated FUS mutation reshapes the RNA and protein composition of stress granules.}, journal = {Nucleic acids research}, volume = {52}, number = {21}, pages = {13269-13289}, pmid = {39494508}, issn = {1362-4962}, support = {ERC-2019-SyG 855923-ASTRA//ERC/ ; IG 2019 Id. 23053//Associazione Italiana per la Ricerca sul Cancro/ ; CN00000041//NextGenerationEU/ ; //Istituto Italiano di Tecnologia/ ; }, mesh = {*RNA-Binding Protein FUS/genetics/metabolism ; *Amyotrophic Lateral Sclerosis/genetics/metabolism ; Humans ; *Mutation ; *Stress Granules/metabolism/genetics ; Cell Line, Tumor ; Transcriptome ; RNA/metabolism/genetics ; RNA, Messenger/metabolism/genetics ; RNA-Binding Proteins/metabolism/genetics ; Cytoplasmic Granules/metabolism/genetics ; }, abstract = {Stress granules (SG) are part of a cellular protection mechanism where untranslated messenger RNAs and RNA-binding proteins are stored upon conditions of cellular stress. Compositional variations due to qualitative or quantitative protein changes can disrupt their functionality and alter their structure. This is the case of different forms of amyotrophic lateral sclerosis (ALS) where a causative link has been proposed between the cytoplasmic de-localization of mutant proteins, such as FUS (Fused in Sarcoma), and the formation of cytotoxic inclusions. Here, we describe the SG transcriptome in neuroblastoma cells and define several features for RNA recruitment in these condensates. We demonstrate that SG dynamics and RNA content are strongly modified by the incorporation of mutant FUS, switching to a more unstructured, AU-rich SG transcriptome. Moreover, we show that mutant FUS, together with its protein interactors and their target RNAs, are responsible for the reshaping of the mutant SG transcriptome with alterations that can be linked to neurodegeneration. Our data describe the molecular differences between physiological and pathological SG in ALS-FUS conditions, showing how FUS mutations impact the RNA and protein composition of these condensates.}, } @article {pmid39494098, year = {2024}, author = {Xu, AX and Zhao, ZF and Zhu, L and Zhang, YH and Li, Y and Wei, YF and Zhang, BY and Jiang, B and Gao, TZ and Li, MS and Liu, JY}, title = {Promise and challenges of traditional Chinese medicine, specifically Calculus bovis, in liver cancer treatment.}, journal = {World journal of gastroenterology}, volume = {30}, number = {40}, pages = {4380-4385}, pmid = {39494098}, issn = {2219-2840}, mesh = {Humans ; Drugs, Chinese Herbal/therapeutic use ; *Liver Neoplasms/therapy/pathology/mortality ; *Medicine, Chinese Traditional/methods ; Neoplasm Staging ; Quality of Life ; Treatment Outcome ; }, abstract = {Liver cancer, one of the most common malignancies worldwide, ranks sixth in incidence and third in mortality. Liver cancer treatment options are diverse, including surgical resection, liver transplantation, percutaneous ablation, transarterial chemoembolization, radiotherapy, chemotherapy, targeted therapy, immunotherapy, and traditional Chinese medicine (TCM). A multidisciplinary team (MDT) is essential to customize treatment plans based on tumor staging, liver function, and performance status (PS), ensuring individualized patient care. Treatment decisions require a MDT to tailor strategies based on tumor staging, liver function, and PS, ensuring personalized care. The approval of new first-line and second-line drugs and the establishment of standard treatments based on immune checkpoint inhibitors have significantly expanded treatment options for advanced liver cancer, improving overall prognosis. However, many patients do not respond effectively to these treatments and ultimately succumb to the disease. Modern oncology treatments, while extending patient survival, often come with severe side effects, resistance, and damage to the body, negatively impacting quality of life. Huang et al's study published at World Journal of Gastroenterology rigorously validates the anticancer properties of Calculus bovis, enhancing our understanding of TCM and contributing to new liver cancer treatment strategies. For over 5000 years, TCM has been used in East Asian countries like China to treat various diseases, including liver conditions. Analysis of real-world clinical data suggests that for patients with advanced-stage tumors lacking effective treatments, integrated TCM therapies could provide significant breakthroughs.}, } @article {pmid39493687, year = {2024}, author = {Kato, N and Hashida, G and Kobayashi, M and Sahara, W}, title = {Characteristics and factors associated with independence in the activities of daily living of patients with amyotrophic lateral sclerosis at diagnosis.}, journal = {Journal of physical therapy science}, volume = {36}, number = {11}, pages = {692-698}, pmid = {39493687}, issn = {0915-5287}, abstract = {[Purpose] To investigate the characteristics and factors associated with independence in the activities of daily living in patients with amyotrophic lateral sclerosis at diagnosis based on clinical phenotypes. [Participants and Methods] Fifty-seven participants diagnosed with amyotrophic lateral sclerosis were assessed using the Barthel Index. Participants were classified into three clinical phenotypes (bulbar-onset, upper limb-onset, and lower limb-onset), and the total and subitem scores were compared. To statistically examine factors associated with independence in the activities of daily living, the participants were divided into two groups: Barthel Index of 100 and ≤95. [Results] The total, bulbar-onset, upper limb-onset, and lower limb-onset Barthel Index scores were 87.9 ± 17.7, 96.7 ± 5.9, 92.5 ± 11.9, and 70.0 ± 22.2, respectively. The Total Barthel Index and lower limb-related activities of daily living scores were significantly lower in the lower limb-onset group, and knee extension muscle strength was identified as a factor associated with independence, with a cutoff value of 32.0%. [Conclusion] Patients with lower limb onset had more impairments in lower limb-related activities of daily living than those with other clinical phenotypes. To maintain independence in patients with amyotrophic lateral sclerosis at diagnosis, it is necessary to improve knee extension muscle strength through exercise and perform environment adjustments using the cutoff values as indicators.}, } @article {pmid39492846, year = {2024}, author = {Matera, AG and Steiner, RE and Mills, CA and McMichael, BD and Herring, LE and Garcia, EL}, title = {Proteomic analysis of the SMN complex reveals conserved and etiologic connections to the proteostasis network.}, journal = {Frontiers in RNA research}, volume = {2}, number = {}, pages = {}, pmid = {39492846}, issn = {2813-7116}, support = {P30 CA016086/CA/NCI NIH HHS/United States ; R35 GM136435/GM/NIGMS NIH HHS/United States ; }, abstract = {INTRODUCTION: Molecular chaperones and co-chaperones are highly conserved cellular components that perform a variety of duties related to the proper three-dimensional folding of the proteome. The web of factors that carries out this essential task is called the proteostasis network (PN). Ribonucleoproteins (RNPs) represent an underexplored area in terms of the connections they make with the PN. The Survival Motor Neuron (SMN) complex is an assembly chaperone and serves as a paradigm for studying how specific RNAs are identified and paired with their client substrate proteins to form RNPs. SMN is the eponymous component of a large complex, required for the biogenesis of uridine-rich small nuclear ribonucleoproteins (U-snRNPs), that localizes to distinct membraneless organelles in both the nucleus and cytoplasm of animal cells. SMN protein forms the oligomeric core of this complex, and missense mutations in the human SMN1 gene are known to cause Spinal Muscular Atrophy (SMA). The basic framework for understanding how snRNAs are assembled into U-snRNPs is known. However, the pathways and mechanisms used by cells to regulate their biogenesis are poorly understood.

METHODS: Given the importance of these processes to normal development as well as neurodegenerative disease, we set out to identify and characterize novel SMN binding partners. We carried out affinity purification mass spectrometry (AP-MS) of Drosophila SMN complexes using fly lines exclusively expressing either wildtype or SMA-causing missense alleles.

RESULTS: Bioinformatic analyses of the pulldown data, along with comparisons to proximity labeling studies carried out in human cells, revealed conserved connections to at least two other major chaperone systems including heat shock folding chaperones (HSPs) and histone/nucleosome assembly chaperones. Notably, we found that heat shock cognate protein Hsc70-4 and other HspA family members preferentially associated with SMA-causing alleles of SMN.

DISCUSSION: Hsc70-4 is particularly interesting because its mRNA is aberrantly sequestered by a mutant form of TDP-43 in mouse and Drosophila ALS (Amyotrophic Lateral Sclerosis) disease models. Most important, a missense allele of Hsc70-4 (HspA8 in mammals) was recently identified as a bypass suppressor of the SMA phenotype in mice. Collectively, these findings suggest that chaperone-related dysfunction lies at the etiological root of both ALS and SMA.}, } @article {pmid39492487, year = {2023}, author = {Xu, L and Ma, Y and Ji, Y and Ma, Y and Wang, Y and Zhao, X and Ge, S}, title = {Obesity exacerbates postoperative cognitive dysfunction by activating the PARP1/NAD[+]/SIRT1 axis through oxidative stress.}, journal = {Experimental gerontology}, volume = {}, number = {}, pages = {112320}, doi = {10.1016/j.exger.2023.112320}, pmid = {39492487}, issn = {1873-6815}, abstract = {The purposes of this study were to explore the impact of obesity on postoperative cognitive dysfunction (POCD) and to investigate the underlying mechanism by which obesity exacerbates POCD. In this study, fifteen-month-old male C57BL/6 J mice were fed a High-fat diet for three months to establish obesity models. Internal fixation of tibial fractures under isoflurane inhalation was performed to construct a POCD animal model. Three days after surgery, mice were subjected to the Morris water maze (MWM) experiment to evaluate their learning and memory abilities. The findings from the MWM experiment revealed that in comparison to the Ad Libitum Surgical group (ALS), mice in the High-fat Surgical group (HFS) exhibited prolonged escape latencies and reduced platform crossings. These outcomes suggest the potential exacerbating role of obesity in cognitive impairment within the POCD mouse models. Immunofluorescence (IF) findings demonstrate that obesity intensifies anesthesia and surgery-induced oxidative stress levels within the hippocampus. Compared to the Ad Libitum Control group (ALC), an elevation in PARP1 expression and a reduction in the NAD[+]/NADH ratio and SIRT1 expression were observed in the hippocampus of mice from the ALS. Moreover, when contrasting the HFS group with the ALS group, increased PARP1 expression along with decreased NAD[+]/NADH ratio and SIRT1 expression were evident. In vitro studies found that compared with the Control group (CON), oil red staining and BODIPY probe staining showed significant lipid droplet aggregation in the palmitic acid (PA) group. IF results demonstrated that HT22 cells in the PA group experienced oxidative stress and activation of the PARP1/NAD[+]/SIRT1 axis in contrast to the CON group. Moreover, manipulation of PARP1 expression in HT22 cells through PARP1 lentivirus-based silencing or overexpression revealed a converse relationship between PARP1 expression levels and the NAD[+]/NADH ratio as well as SIRT1 expression levels. This study concludes that obesity may exacerbate POCD by triggering activation of the oxidative stress-induced PARP1/NAD[+]/SIRT1 axis.}, } @article {pmid39492438, year = {2023}, author = {Hamzeh, O and Rabiei, F and Shakeri, M and Parsian, H and Saadat, P and Rostami-Mansoor, S}, title = {Mitochondrial dysfunction and inflammasome activation in neurodegenerative diseases: Mechanisms and therapeutic implications.}, journal = {Mitochondrion}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.mito.2023.10.003}, pmid = {39492438}, issn = {1872-8278}, abstract = {Impaired mitochondrial function is crucial to the pathogenesis of several neurodegenerative diseases. It causes the release of mitochondrial DNA (mtDNA), mitochondrial reactive oxygen species (mtROS), ATP, and cardiolipin, which activate the nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 (NLRP3) inflammasome. NLRP3 inflammasome is an important innate immune system element contributing to neuroinflammation and neurodegeneration. Therefore, targeting the NLRP3 inflammasome has become an interesting therapeutic approach for treating neurodegenerative diseases. This review describes the role of mitochondrial abnormalities and over-activated inflammasomes in the progression of neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), Multiple sclerosis (MS), Amyotrophic lateral sclerosis (ALS), and Friedrich ataxia (FRDA). We also discuss the therapeutic strategies focusing on signaling pathways associated with inflammasome activation, which potentially alleviate neurodegenerative symptoms and impede disease progression.}, } @article {pmid39492095, year = {2023}, author = {Mohammadi, S and Mohammadi, M and Ghaderi, S}, title = {Sleep-related regions in neurodegenerative diseases by central nervous system localization using magnetic resonance imaging.}, journal = {Psychiatry research. Neuroimaging}, volume = {336}, number = {}, pages = {111727}, doi = {10.1016/j.pscychresns.2023.111727}, pmid = {39492095}, issn = {1872-7506}, abstract = {Sleep disruptions associated with neurodegenerative diseases (NDDs) damage the brain's sleep-regulating regions. Advanced magnetic resonance imaging (MRI) techniques can characterize the signature of each neurodegenerative pathology. We performed an evaluation of sleep-related regions in NDDs using MRI to localize the central nervous system (CNS). In the initial search, 61 related papers were discovered using predetermined inclusion and exclusion criteria. Finally, 30 articles were included in this study. The study included patients with Parkinson's disease (PD), Alzheimer's disease (AD), multiple sclerosis (MS), rapid eye movement (REM) sleep behavior disorder (RBD), idiopathic RBD (iRBD), amyotrophic lateral sclerosis (ALS), and mild cognitive impairment (MCI). Sleep-related regions recognized by CNS localization in NDDs can be linked to important regions. MRI also revealed cortical thinning, GM atrophy, WM, and tract loss, changes in diffusion tensor imaging (DTI) biomarkers (fractional anisotropy (FA), axial diffusivity (Da), and radial diffusivity (Dr)), a decrease in DMN connectivity, a reduction in functional connectivity (FC), and amplitude of low-frequency fluctuation (ALFF) alterations. Sleep plays an important role in predicting future risks for the development of NDDs. Other neuroimaging, cognitive-behavioral, and clinical research can use the information found in this research about the brain regions, MRI biomarker changes, and their relationships.}, } @article {pmid39491718, year = {2024}, author = {Sharma, R and Khan, Z and Mehan, S and Das Gupta, G and Narula, AS}, title = {Unraveling the multifaceted insights into amyotrophic lateral sclerosis: Genetic underpinnings, pathogenesis, and therapeutic horizons.}, journal = {Mutation research. Reviews in mutation research}, volume = {794}, number = {}, pages = {108518}, doi = {10.1016/j.mrrev.2024.108518}, pmid = {39491718}, issn = {1388-2139}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/therapy ; Mutation/genetics ; RNA-Binding Protein FUS/genetics ; C9orf72 Protein/genetics ; Animals ; Superoxide Dismutase-1/genetics ; DNA-Binding Proteins/genetics ; Genetic Predisposition to Disease ; }, abstract = {Amyotrophic Lateral Sclerosis (ALS), a progressive neurodegenerative disease, primarily impairs upper and lower motor neurons, leading to debilitating motor dysfunction and eventually respiratory failure, widely known as Lou Gehrig's disease. ALS presents with diverse symptomatology, including dysarthria, dysphagia, muscle atrophy, and hyperreflexia. The prevalence of ALS varies globally, with incidence rates ranging from 1.5 to 3.8 per 100,000 individuals, significantly affecting populations aged 45-80. A complex interplay of genetic and environmental factors underpins ALS pathogenesis. Key genetic contributors include mutations in chromosome 9 open reading frame 72 (C9ORF72), superoxide dismutase type 1 (SOD1), Fusedin sarcoma (FUS), and TAR DNA-binding protein (TARDBP) genes, accounting for a considerable fraction of both familial (fALS) and sporadic (sALS) cases. The disease mechanism encompasses aberrant protein folding, mitochondrial dysfunction, oxidative stress, excitotoxicity, and neuroinflammation, contributing to neuronal death. This review consolidates current insights into ALS's multifaceted etiology, highlighting the roles of environmental exposures (e.g., toxins, heavy metals) and their interaction with genetic predispositions. We emphasize the polygenic nature of ALS, where multiple genetic variations cumulatively influence disease susceptibility and progression. This aspect underscores the challenges in ALS diagnosis, which currently lacks specific biomarkers and relies on symptomatology and familial history. Therapeutic strategies for ALS, still in nascent stages, involve symptomatic management and experimental approaches targeting molecular pathways implicated in ALS pathology. Gene therapy, focusing on specific ALS mutations, and stem cell therapy emerge as promising avenues. However, effective treatments remain elusive, necessitating a deeper understanding of ALS's genetic architecture and the development of targeted therapies based on personalized medicine principles. This review aims to provide a comprehensive understanding of ALS, encouraging further research into its complex genetic underpinnings and the development of innovative, effective treatment modalities.}, } @article {pmid39491634, year = {2024}, author = {Tedeschi, V and Nele, V and Valsecchi, V and Anzilotti, S and Vinciguerra, A and Zucaro, L and Sisalli, MJ and Cassiano, C and De Iesu, N and Pignataro, G and Canzoniero, LMT and Pannaccione, A and De Rosa, G and Secondo, A}, title = {Nanoparticles encapsulating phosphatidylinositol derivatives promote neuroprotection and functional improvement in preclinical models of ALS via a long-lasting activation of TRPML1 lysosomal channel.}, journal = {Pharmacological research}, volume = {210}, number = {}, pages = {107491}, doi = {10.1016/j.phrs.2024.107491}, pmid = {39491634}, issn = {1096-1186}, mesh = {*Amyotrophic Lateral Sclerosis/drug therapy/metabolism/physiopathology ; Animals ; *Transient Receptor Potential Channels/metabolism ; *Lysosomes/drug effects/metabolism ; *Motor Neurons/drug effects/metabolism ; *Disease Models, Animal ; Neuroprotective Agents/pharmacology/therapeutic use ; Mice, Transgenic ; Humans ; Mice ; Phosphatidylinositols/metabolism ; Phosphatidylinositol Phosphates/metabolism ; Male ; Mice, Inbred C57BL ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease currently incurable, in which motor neuron degeneration leads to voluntary skeletal muscle atrophy. Molecularly, ALS is characterized by protein aggregation, synaptic and organellar dysfunction, and Ca[2+] dyshomeostasis. Of interest, autophagy dysfunction is emerging as one of the main putative targets of ALS therapy. A tune regulation of this cleansing process is affordable by a proper stimulation of TRPML1, one of the main lysosomal channels. However, TRPML1 activation by PI(3,5)P2 has low open probability to remain in an active conformation. To overcome this drawback we developed a lipid-based formulation of PI(3,5)P2 whose putative therapeutic potential has been tested in in vitro and in vivo ALS models. Pharmacodynamic properties of PI(3,5)P2 lipid-based formulations (F1 and F2) on TRPML1 activity have been characterized by means of patch-clamp electrophysiology and Fura-2AM video-imaging in motor neuronal cells. Once selected for the ability to stabilize TRPML1 activity, the most effective preparation F1 was studied in vivo to measure neuromuscular function and survival of SOD1[G93A] ALS mice, thereby establishing its therapeutic profile. F1, but not PI(3,5)P2 alone, stabilized the open state of the lysosomal channel TRPML1 and increased the persistence of intracellular calcium concentration ([Ca[2+]]i). Then, F1 was effective in delaying motor neuron loss, improving innervated endplants and muscle performance in SOD1[G93A] mice, extending overall lifespan by an average of 10 days. Of note F1 prevented gliosis and autophagy dysfunction in ALS mice by restoring PI(3,5)P2 level. Our novel self-assembling lipidic formulation for PI(3,5)P2 delivery exerts a neuroprotective effect in preclinical models of ALS mainly regulating dysfunctional autophagy through TRPML1 activity stabilization.}, } @article {pmid39491419, year = {2023}, author = {Talebi, M and Sadoughi, MM and Ayatollahi, SA and Ainy, E and Kiani, R and Zali, A and Miri, M}, title = {Therapeutic potentials of cannabidiol: Focus on the Nrf2 signaling pathway.}, journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie}, volume = {168}, number = {}, pages = {115805}, doi = {10.1016/j.biopha.2023.115805}, pmid = {39491419}, issn = {1950-6007}, abstract = {Cannabidiol (CBD), a cannabinoid that does not create psychoactive activities, has been identified as having a multitude of therapeutic benefits. This study delves into the chemical properties, pharmacokinetics, safety and toxicity, pharmacological effects, and most importantly, the association between the therapeutic potential of CBD and the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway. The relationship between Nrf2 and CBD is closely linked to certain proteins that are associated with cardiovascular dysfunctions, cancers, and neurodegenerative conditions. Specifically, Nrf2 is connected to the initiation and progression of diverse health issues, including nephrotoxicity, bladder-related diseases, oral mucositis, cancers, obesity, myocardial injury and angiogenesis, skin-related inflammations, psychotic disorders, neuropathic pain, Huntington's disease, Alzheimer's disease, Parkinson's disease, neuroinflammation, Amyotrophic Lateral Sclerosis, and Multiple Sclerosis. The association between CBD and Nrf2 is a zone of great interest in the medical field, as it has the potential to significantly impact the treatment and prevention of wide-ranging health conditions. Additional investigation is necessary to entirely apprehend the mechanisms underlying this crucial interplay and to develop effective therapeutic interventions.}, } @article {pmid39491120, year = {2023}, author = {Stachel, SJ and Wang, D and Ginnetti, AT and Niroomand, S and Ma, L and Hu, Y and Fay, JF and Lemaire, W and Krosky, DJ and Ramirez, AD and Zariwala, HA and Coleman, PJ}, title = {Virtual screening for early identification of potent and selective histone deacetylase 6 inhibitor series.}, journal = {Bioorganic & medicinal chemistry letters}, volume = {}, number = {}, pages = {129537}, doi = {10.1016/j.bmcl.2023.129537}, pmid = {39491120}, issn = {1464-3405}, abstract = {Virtual screening was leveraged to identify novel series of histone deacetylase 6 (HDAC6) inhibitors prior to conducting a high-throughput screen. The virtual screen was designed to augment and expand on chemical matter that would otherwise be unavailable for high-throughput screening. Through this effort we succeeded in identifying four novel, potent and highly selective HDAC6 inhibitor series. These series displayed favorable ligand binding efficiencies and good potential for further optimization. The virtual design specifications and results are discussed herein.}, } @article {pmid39490684, year = {2024}, author = {Liu, YJ and Lee, CW and Liao, YC and Huang, JJ and Kuo, HC and Jih, KY and Lee, YC and Chern, Y}, title = {The role of adiponectin-AMPK axis in TDP-43 mislocalization and disease severity in ALS.}, journal = {Neurobiology of disease}, volume = {202}, number = {}, pages = {106715}, doi = {10.1016/j.nbd.2024.106715}, pmid = {39490684}, issn = {1095-953X}, mesh = {*Amyotrophic Lateral Sclerosis/metabolism ; Humans ; *Adiponectin/metabolism ; *DNA-Binding Proteins/metabolism ; Male ; Female ; Middle Aged ; *AMP-Activated Protein Kinases/metabolism ; Aged ; Motor Neurons/metabolism ; Severity of Illness Index ; }, abstract = {Hypermetabolism is a prominent characteristic of ALS patients. Aberrant activation of AMPK, an energy sensor regulated by adiponectin, is known to cause TDP-43 mislocalization, an early event in ALS pathogenesis. This study aims to evaluate the association between key energy mediators and clinical severity in ALS patients. We found that plasma adiponectin levels were significantly higher in ALS patients with ALSFRS-R scores below 38 compared to controls (p = 0.047). Additionally, adiponectin concentration was inversely correlated with ALSFRS-R scores (p = 0.021). Immunofluorescence staining of PBMCs revealed negative associations between AMPK activation, TDP-43 mislocalization, and ALSFRS-R scores. We then examined the hypothesis that adiponectin may activate the AMPK-TDP-43 axis in motor neurons. Our results demonstrated that adiponectin treatment of NSC34 cells and HiPSC-MNs induced AMPK activation and TDP-43 mislocalization in an adiponectin receptor-dependent manner. Collectively, these findings suggest that elevated plasma adiponectin may enhance AMPK activation, leading to TDP-43 mislocalization in both PBMCs and motor neurons of ALS patients. This highlights the potential involvement of the adiponectin-AMPK-TDP-43 axis in the dysregulated energy balance observed in ALS.}, } @article {pmid39490682, year = {2024}, author = {Leykam, L and Forsberg, KME and Nordström, U and Hjertkvist, K and Öberg, A and Jonsson, E and Andersen, PM and Marklund, SL and Zetterström, P}, title = {Specific analysis of SOD1 enzymatic activity in CSF from ALS patients with and without SOD1 mutations.}, journal = {Neurobiology of disease}, volume = {202}, number = {}, pages = {106718}, doi = {10.1016/j.nbd.2024.106718}, pmid = {39490682}, issn = {1095-953X}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/cerebrospinal fluid ; *Superoxide Dismutase-1/genetics ; Male ; *Mutation ; Female ; Middle Aged ; Superoxide Dismutase/genetics/cerebrospinal fluid ; Adult ; Aged ; }, abstract = {Mutations in superoxide dismutase-1 (SOD1) are a cause of hereditary amyotrophic lateral sclerosis (ALS) through a gain-of-function mechanism involving unfolded mutant SOD1. Intrathecal gene therapy using the antisense-oligo-nucleotide drug tofersen to reduce SOD1 expression delays disease progression and has recently been approved in the United States and the European Union. However, the discovery of children homozygous for inactivating SOD1 mutations developing the SOD1 Deficiency Syndrome (ISODDES) with injury to the motor system suggests that a too low SOD1 antioxidant activity may be deleterious in humans. Measuring SOD1 activity in cerebrospinal fluid (CSF) in tofersen-treated patients is recommended but difficult due to low concentration and the presence of the isoenzyme SOD3. We here present a sensitive method to assess SOD1 activity by removing SOD3 from CSF samples using highly specific immobilized antibodies and subsequent measurement of the SOD activity. We validated the method on 171 CSF samples from ALS patients with and without mutations and controls and used paired erythrocyte samples for comparison. We found that in ALS patients with wildtype SOD1, the SOD1 activity in CSF was equal to controls, but patients with mutant SOD1 show lower activity in CSF, even for patients with mutants previously reported to have full activity in erythrocytes. Activity variation in CSF was large among patients carrying the same SOD1 mutation and larger than in erythrocytes and in post-mortem nervous tissue. Additionally, we identified a discrepancy between the SOD1 activity and protein level measured with ELISA in both CSF and erythrocytes. Since antibodies used for SOD1 ELISA-quantification are raised against the natively folded wildtype SOD1, the concentration of mutant SOD1s may be underestimated. Analysis of SOD1 enzymatic activity in CSF is therefore a more reliable way to monitor the effect of SOD1-lowering drugs.}, } @article {pmid39490400, year = {2024}, author = {Zhang, Y and Zou, M and Wu, H and Zhu, J and Jin, T}, title = {The cGAS-STING pathway drives neuroinflammation and neurodegeneration via cellular and molecular mechanisms in neurodegenerative diseases.}, journal = {Neurobiology of disease}, volume = {202}, number = {}, pages = {106710}, doi = {10.1016/j.nbd.2024.106710}, pmid = {39490400}, issn = {1095-953X}, mesh = {Humans ; *Nucleotidyltransferases/metabolism ; *Membrane Proteins/metabolism ; *Neurodegenerative Diseases/metabolism ; *Signal Transduction/physiology ; Animals ; *Neuroinflammatory Diseases/metabolism ; }, abstract = {Neurodegenerative diseases (NDs) are a type of common chronic progressive disorders characterized by progressive damage to specific cell populations in the nervous system, ultimately leading to disability or death. Effective treatments for these diseases are still lacking, due to a limited understanding of their pathogeneses, which involve multiple cellular and molecular pathways. The triggering of an immune response is a common feature in neurodegenerative disorders. A critical challenge is the intricate interplay between neuroinflammation, neurodegeneration, and immune responses, which are not yet fully characterized. In recent years, the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon gene (STING) pathway, a crucial immune response for intracellular DNA sensing, has gradually gained attention. However, the specific roles of this pathway within cellular types such as immune cells, glial and neuronal cells, and its contribution to ND pathogenesis, remain not fully elucidated. In this review, we systematically explore how the cGAS-STING signaling links various cell types with related cellular effector pathways under the context of NDs for multifaceted therapeutic directions. We emphasize the discovery of condition-dependent cellular heterogeneity in the cGAS-STING pathway, which is integral for understanding the diverse cellular responses and potential therapeutic targets. Additionally, we review the pathogenic role of cGAS-STING activation in Parkinson's disease, ataxia-telangiectasia, and amyotrophic lateral sclerosis. We focus on the complex bidirectional roles of the cGAS-STING pathway in Alzheimer's disease, Huntington's disease, and multiple sclerosis, revealing their double-edged nature in disease progression. The objective of this review is to elucidate the pivotal role of the cGAS-STING pathway in ND pathogenesis and catalyze new insights for facilitating the development of novel therapeutic strategies.}, } @article {pmid39489870, year = {2024}, author = {Van Weehaeghe, D and Devrome, M and de Vocht, J and Masrori, P and Schramm, G and Deckers, W and Baete, K and De Weerdt, C and Van Damme, P and Koole, M and Van Laere, K}, title = {Combined brain and spinal FDG PET in the differentiation between ALS and ALS mimics - correction and additional validation study.}, journal = {European journal of nuclear medicine and molecular imaging}, volume = {52}, number = {1}, pages = {109-112}, pmid = {39489870}, issn = {1619-7089}, } @article {pmid39489397, year = {2024}, author = {Desouky, MA and Michel, HE and Elsherbiny, DA and George, MY}, title = {Recent pharmacological insights on abating toxic protein species burden in neurological disorders: Emphasis on 26S proteasome activation.}, journal = {Life sciences}, volume = {359}, number = {}, pages = {123206}, doi = {10.1016/j.lfs.2024.123206}, pmid = {39489397}, issn = {1879-0631}, mesh = {*Proteasome Endopeptidase Complex/metabolism ; Humans ; Animals ; Neurodegenerative Diseases/metabolism/drug therapy ; Nervous System Diseases/drug therapy/metabolism ; Proteolysis/drug effects ; Signal Transduction/drug effects ; Proteostasis/drug effects ; Ubiquitin/metabolism ; }, abstract = {Protein homeostasis (proteostasis) refers to the plethora of mechanisms that safeguard the proper folding of the newly synthesized proteins. It entails various intricately regulated cues that demolish the toxic protein species to prevent their aggregation. The ubiquitin-proteasome system (UPS) is recognized as a salient protein degradation system, with a substantial role in maintaining proteostasis. However, under certain circumstances the protein degradation capacity of the UPS is overwhelmed, leading to the accumulation of misfolded proteins. Several neurodegenerative disorders, such as Alzheimer's disease, Parkinson's disease, Huntington disease, and amyotrophic lateral sclerosis are characterized with the presence of protein aggregates and proteinopathy. Accordingly, enhancing the 26S proteasome degradation activity might delineate a pioneering approach in targeting various proteotoxic disorders. Regrettably, the exact molecular approaches that enhance the proteasomal activity are still not fully understood. Therefore, this review aimed to underscore several signaling cascades that might restore the degradation capacity of this molecular machine. In this review, we discuss the different molecular components of the UPS and how 26S proteasomes are deleteriously affected in many neurodegenerative diseases. Moreover, we summarize different signaling pathways that can be utilized to renovate the 26S proteasome functional capacity, alongside currently known druggable targets in this circuit and various classes of proteasome activators.}, } @article {pmid39487163, year = {2024}, author = {Cai, S and Venugopalan, S and Seaver, K and Xiao, X and Tomanek, K and Jalasutram, S and Morris, MR and Kane, S and Narayanan, A and MacDonald, RL and Kornman, E and Vance, D and Casey, B and Gleason, SM and Nelson, PQ and Brenner, MP}, title = {Using large language models to accelerate communication for eye gaze typing users with ALS.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {9449}, pmid = {39487163}, issn = {2041-1723}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology ; *Communication Devices for People with Disabilities ; Female ; Male ; Pilot Projects ; *Fixation, Ocular/physiology ; Language ; Adult ; User-Computer Interface ; Middle Aged ; Communication ; }, abstract = {Accelerating text input in augmentative and alternative communication (AAC) is a long-standing area of research with bearings on the quality of life in individuals with profound motor impairments. Recent advances in large language models (LLMs) pose opportunities for re-thinking strategies for enhanced text entry in AAC. In this paper, we present SpeakFaster, consisting of an LLM-powered user interface for text entry in a highly-abbreviated form, saving 57% more motor actions than traditional predictive keyboards in offline simulation. A pilot study on a mobile device with 19 non-AAC participants demonstrated motor savings in line with simulation and relatively small changes in typing speed. Lab and field testing on two eye-gaze AAC users with amyotrophic lateral sclerosis demonstrated text-entry rates 29-60% above baselines, due to significant saving of expensive keystrokes based on LLM predictions. These findings form a foundation for further exploration of LLM-assisted text entry in AAC and other user interfaces.}, } @article {pmid39486809, year = {2024}, author = {Van Loon, FT and Seitidis, G and Mavridis, D and van Unnik, JWJ and Weemering, DN and van den Berg, LH and Bethani, I and Nikolakopoulos, S and van Eijk, RPA}, title = {Living systematic review and comprehensive network meta-analysis of ALS clinical trials: study protocol.}, journal = {BMJ open}, volume = {14}, number = {10}, pages = {e087970}, pmid = {39486809}, issn = {2044-6055}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy ; *Clinical Trials as Topic ; Disease Progression ; Research Design ; Systematic Reviews as Topic ; Network Meta-Analysis as Topic ; }, abstract = {INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a fatal neurogenerative disease with no effective treatment to date. Despite numerous clinical trials, the majority of studies have been futile in their effort to significantly alter the course of the disease. However, these studies may still provide valuable information for identifying patient subgroups and generating new hypotheses for future research. Additionally, synthesising evidence from these studies may help overcome the limitations of individual studies. Network meta-analysis may refine the assessment of efficacy in specific patient subgroups, evaluate intervention characteristics such as mode of administration or biological mechanisms of action, and rank order promising therapeutic areas of interest. Therefore, we aim to synthesise the available evidence from ALS clinical trials.

METHODS AND ANALYSIS: We will conduct a systematic review to identify all clinical trials that assessed disease-modifying pharmaceutical therapies, cell therapies, or supplements in patients with ALS. Outcomes of interest are clinical disease progression outcomes and survival. We will conduct this search in the period Q4 2024 in three databases: PubMed, Embase and ClinicalTrials.gov for studies from 1999 to 2023. Individual patient data and aggregate data will be collected and subsequentially synthesised in meta-analytical models. The final model will be presented as an open-source web application with biannual updates of the underlying data, thereby providing a 'living' overview of the ALS clinical trial landscape.

ETHICS AND DISSEMINATION: No ethics approvals are required. Findings will be presented at relevant conferences and submitted to peer-reviewed journals. Data will be stored anonymously in secure repositories.}, } @article {pmid39484239, year = {2024}, author = {Leinders, S and Aarnoutse, EJ and Branco, MP and Freudenburg, ZV and Geukes, SH and Schippers, A and Verberne, MSW and van den Boom, M and van der Vijgh, B and Crone, NE and Denison, T and Ramsey, NF and Vansteensel, MJ}, title = {DO NOT LOSE SLEEP OVER IT: IMPLANTED BRAIN-COMPUTER INTERFACE FUNCTIONALITY DURING NIGHTTIME IN LATE-STAGE AMYOTROPHIC LATERAL SCLEROSIS.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, pmid = {39484239}, support = {U01 DC016686/DC/NIDCD NIH HHS/United States ; UH3 NS114439/NS/NINDS NIH HHS/United States ; }, abstract = {BACKGROUND AND OBJECTIVES: Brain-computer interfaces (BCIs) hold promise as augmentative and alternative communication technology for people with severe motor and speech impairment (locked-in syndrome) due to neural disease or injury. Although such BCIs should be available 24/7, to enable communication at all times, feasibility of nocturnal BCI use has not been investigated. Here, we addressed this question using data from an individual with amyotrophic lateral sclerosis (ALS) who was implanted with an electrocorticography-based BCI that enabled the generation of click-commands for spelling words and call-caregiver signals.

METHODS: We investigated nocturnal dynamics of neural signal features used for BCI control, namely low (LFB: 10-30Hz) and high frequency band power (HFB: 65-95Hz). Additionally, we assessed the nocturnal performance of a BCI decoder that was trained on daytime data by quantifying the number of unintentional BCI activations at night. Finally, we developed and implemented a nightmode decoder that allowed the participant to call a caregiver at night, and assessed its performance.

RESULTS: Power and variance in HFB and LFB were significantly higher at night than during the day in the majority of the nights, with HFB variance being higher in 88% of nights. Daytime decoders caused 245 unintended selection-clicks and 13 unintended caregiver-calls per hour when applied to night data. The developed nightmode decoder functioned error-free in 79% of nights over a period of ±1.5 years, allowing the user to reliably call the caregiver, with unintended activations occurring only once every 12 nights.

DISCUSSION: Reliable nighttime use of a BCI requires decoders that are adjusted to sleep-related signal changes. This demonstration of a reliable BCI nightmode and its long-term use by an individual with advanced ALS underscores the importance of 24/7 BCI reliability.

TRIAL REGISTRATION: This trial is registered in clinicaltrials.gov under number NCT02224469 (https://clinicaltrials.gov/study/NCT02224469?term=NCT02224469&rank=1). Date of submission to registry: August 21, 2014. Enrollment of first participant: September 7, 2015.}, } @article {pmid39483635, year = {2024}, author = {Murakami, Y and Ando, M and Imamura, A and Oketani, R and Leproux, P and Honjoh, S and Kano, H}, title = {Molecular Fingerprinting of Mouse Brain Using Ultrabroadband Coherent Anti-Stokes Raman Scattering (CARS) Microspectroscopy Empowered by Multivariate Curve Resolution-Alternating Least Squares (MCR-ALS).}, journal = {Chemical & biomedical imaging}, volume = {2}, number = {10}, pages = {689-697}, pmid = {39483635}, issn = {2832-3637}, abstract = {The Raman fingerprint spectral region provides abundant structural information on molecules. However, analyzing vibrational images within this region using coherent Raman imaging remains challenging due to the small Raman cross section and congested spectral features. In this study, we combined ultrabroadband coherent anti-Stokes Raman scattering (CARS) microspectroscopy across the spectral range of 500-4000 cm[-1] with multivariate curve resolution-alternating least-squares (MCR-ALS) to reveal hidden Raman bands in the fingerprint region. Applying this method to mouse brain tissue, we extracted information on cholesterol and collagen, leveraging their distinctive molecular signatures, as well as on key molecules such as lipids, proteins, water, and nucleic acids. Moreover, the simultaneous detection of second harmonic generation facilitated label-free visualization of organelles, including arachnoid membrane and Rootletin filaments.}, } @article {pmid39483234, year = {2024}, author = {Fujimoto, A and Kinjo, M and Kitamura, A}, title = {Short Repeat Ribonucleic Acid Reduces Cytotoxicity by Preventing the Aggregation of TDP-43 and Its 25 KDa Carboxy-Terminal Fragment.}, journal = {JACS Au}, volume = {4}, number = {10}, pages = {3896-3909}, pmid = {39483234}, issn = {2691-3704}, abstract = {TAR DNA/RNA-binding protein 43 kDa (TDP-43) proteinopathy is a hallmark of neurodegenerative disorders, such as amyotrophic lateral sclerosis, in which cytoplasmic aggregates containing TDP-43 and its C-terminal fragments, such as TDP-25, are observed in degenerative neuronal cells. However, few reports have focused on small molecules that can reduce their aggregation and cytotoxicity. Here, we show that short RNA repeats of GGGGCC and AAAAUU are aggregation suppressors of TDP-43 and TDP-25. TDP-25 interacts with these RNAs, as well as TDP-43, despite the lack of major RNA-recognition motifs using fluorescence cross-correlation spectroscopy. Expression of these RNAs significantly decreases the number of cells harboring cytoplasmic aggregates of TDP-43 and TDP-25 and ameliorates cell death by TDP-25 and mislocalized TDP-43 without altering the cellular transcriptome of molecular chaperones. Consequently, short RNA repeats of GGGGCC and AAAAUU can maintain proteostasis by preventing the aggregation of TDP-43 and TDP-25.}, } @article {pmid39488863, year = {2024}, author = {Lopes, M and Swash, M and de Carvalho, M}, title = {F-waves responses derived from low-intensity electrical stimulation: A method to explore split-hand pathogenesis.}, journal = {Neurophysiologie clinique = Clinical neurophysiology}, volume = {54}, number = {6}, pages = {103018}, doi = {10.1016/j.neucli.2024.103018}, pmid = {39488863}, issn = {1769-7131}, mesh = {Humans ; Male ; Female ; *Hand/physiopathology ; Adult ; *Muscle, Skeletal/physiopathology/physiology ; *Electric Stimulation/methods ; Middle Aged ; Motor Neurons/physiology ; Electromyography ; Amyotrophic Lateral Sclerosis/physiopathology/therapy ; Young Adult ; Evoked Potentials, Motor/physiology ; Aged ; }, abstract = {OBJECTIVES: The "split-hand syndrome" is a common clinical sign in amyotrophic lateral sclerosis (ALS), being characterized by more severe atrophy of the hand muscles on the radial side of the hand compared to the ulnar side. We aimed to investigate possible physiological differences between relevant hand muscles using low-intensity F-wave stimulation to assess spinal motoneuron excitability.

METHODS: We recruited 36 healthy volunteers. F-waves were recorded from the abductor pollicis brevis (APB), first dorsal interosseous (FDI) and abductor digiti minimi (ADM), using 20 supramaximal stimuli followed by 20 stimuli at a low-intensity required to obtain M-waves with 10 % amplitude of maximal CMAP. We evaluated the following F-wave parameters: F-M latency, chronodispersion, persistence, amplitude, F/CMAP amplitude ratio and number of F-wave repeaters (with low-intensity). In 10 subjects, low-intensity stimulation F-waves were compared after 20 and 50 stimuli in each muscle.

RESULTS: Low-intensity stimulation resulted in lower F-wave amplitude and persistence and higher F/CMAP amplitude ratios. There were no significant differences in F-wave latencies and chronodispersion. When comparing the three muscles, we found higher F-wave persistence and F/CMAP amplitude ratios when recording over the ADM and APB compared to the FDI. We also found a higher number of F-wave repeaters in the ADM with low-intensity stimulation. Results from 20 to 50 low-intensity stimuli were similar.

DISCUSSION: A small number of low-intensity stimuli is appropriate to study F-wave latencies and chronodispersion. We found differences in some physiological properties of the ADM spinal motoneuron pool compared to other hand muscles.}, } @article {pmid39480764, year = {2024}, author = {Perrin, S and Ladha, S and Maragakis, N and Rivner, MH and Katz, J and Genge, A and Olney, N and Lange, D and Heitzman, D and Bodkin, C and Jawdat, O and Goyal, NA and Bornstein, JD and Mak, C and Appel, SH and Paganoni, S}, title = {Safety and tolerability of tegoprubart in patients with amyotrophic lateral sclerosis: A Phase 2A clinical trial.}, journal = {PLoS medicine}, volume = {21}, number = {10}, pages = {e1004469}, pmid = {39480764}, issn = {1549-1676}, mesh = {Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; *Amyotrophic Lateral Sclerosis/drug therapy/immunology ; Antibodies, Monoclonal/adverse effects/administration & dosage/therapeutic use ; Antibodies, Monoclonal, Humanized/adverse effects/administration & dosage/therapeutic use/pharmacokinetics ; Biomarkers/blood ; CD40 Ligand/blood ; Disease Progression ; Dose-Response Relationship, Drug ; Neurofilament Proteins/blood ; Pyrazines ; Treatment Outcome ; Imidazoles ; }, abstract = {BACKGROUND: The interaction of CD40L and its receptor CD40 on activated T cells and B cells respectively control pro-inflammatory activation in the pathophysiology of autoimmunity and transplant rejection. Previous studies have implicated signaling pathways involving CD40L (interchangeably referred to as CD154), as well as adaptive and innate immune cell activation, in the induction of neuroinflammation in neurodegenerative diseases. This study aimed to assess the safety, tolerability, and impact on pro-inflammatory biomarker profiles of an anti CD40L antibody, tegoprubart, in individuals with amyotrophic lateral sclerosis (ALS).

METHODS AND FINDINGS: In this multicenter dose-escalating open-label Phase 2A study, 54 participants with a diagnosis of ALS received 6 infusions of tegoprubart administered intravenously every 2 weeks. The study was comprised of 4 dose cohorts: 1 mg/kg, 2 mg/kg, 4 mg/kg, and 8 mg/kg. The primary endpoint of the study was safety and tolerability. Exploratory endpoints assessed the pharmacokinetics of tegoprubart as well as anti-drug antibody (ADA) responses, changes in disease progression utilizing the Revised ALS Functional Rating Scale (ALSFRS-R), CD154 target engagement, changes in pro-inflammatory biomarkers, and neurofilament light chain (NFL). Seventy subjects were screened, and 54 subjects were enrolled in the study. Forty-nine of 54 subjects completed the study (90.7%) receiving all 6 infusions of tegoprubart and completing their final follow-up visit. The most common treatment emergent adverse events (TEAEs) overall (>10%) were fatigue (25.9%), falls (22.2%), headaches (20.4%), and muscle spasms (11.1%). Mean tegoprubart plasma concentrations increased proportionally with increasing dose with a half-life of approximately 24 days. ADA titers were low and circulating levels of tegoprubart were as predicted for all cohorts. Tegoprubart demonstrated dose dependent target engagement associated and a reduction in 18 pro-inflammatory biomarkers in circulation.

CONCLUSIONS: Tegoprubart appeared to be safe and well tolerated in adults with ALS demonstrating dose-dependent reduction in pro-inflammatory chemokines and cytokines associated with ALS. These results warrant further clinical studies with sufficient power and duration to assess clinical outcomes as a potential treatment for adults with ALS.

TRIAL REGISTRATION: Clintrials.gov ID:NCT04322149.}, } @article {pmid39480562, year = {2025}, author = {Cao, G and Wang, S and Yu, J and Wang, X and Shi, X and Yang, L and Zhang, X and Tong, P and Tan, H}, title = {Outcomes of combined single-bundle anterior cruciate ligament reconstruction and anterolateral structure reconstruction through a modified single femoral tunnel.}, journal = {International orthopaedics}, volume = {49}, number = {1}, pages = {83-91}, pmid = {39480562}, issn = {1432-5195}, support = {82104896//National Natural Science Foundation of China/ ; 242102310025//Henan Provincial Science and Technology Research Project/ ; 2024HLTJ17//Heluo Youth Talent Support Program/ ; }, mesh = {Humans ; Male ; Female ; *Anterior Cruciate Ligament Reconstruction/methods ; Adult ; Middle Aged ; Young Adult ; Adolescent ; *Femur/surgery ; *Anterior Cruciate Ligament Injuries/surgery ; Treatment Outcome ; Arthroscopy/methods ; Hamstring Tendons/transplantation ; Transplantation, Autologous/methods ; }, abstract = {PURPOSE: To explore the clinical outcomes of combining anterior cruciate ligament (ACL) reconstruction and anterolateral structure (ALS) reconstruction through a modified single femoral tunnel in patients with high risk of clinical failure.

METHODS: From December 2018 to August 2022, a total of 62 patients with ACL injury in our institution were enrolled in this study. All patients were associated with high risk of clinical failure, meeting the indications of ALS reconstruction. All patients accepted arthroscopic single-bundle ACL reconstruction and ALS reconstruction using hamstring autograft through a modified single femoral tunnel. Perioperative clinical outcome measurements consisted of functions, stability and safety evaluation at different time points (preoperative, postoperative three month, six month, one year, two year, three year and more). Functional evaluation included Lysholm score, Tegner activity scale, subjective and objective International Knee Documentation Committee (IKDC) score.

RESULTS: All patients, including 47 males and 15 females, aged 16-52 years with an average age of 29.3 ± 9.2 years, were followed up for 12-58 months. At the last follow-up, the Lysholm, subjective IKDC and Tegner activity scale (93.8 ± 7.0, 88.8 ± 10.7 and 5.8 ± 1.4 respectively) were significantly higher than those before surgery (65.0 ± 20.8, 51.2 ± 21.1 and 2.3 ± 1.3 respectively)(P < 0.05). Postoperative pivot shift and Lachman test were markedly improved (P < 0.05). One patient still had grade II pivot shift, defined as clinical failure. During follow-up, no graft rupture occurred according to magnetic resonance imaging and physical examination, no lateral compartment osteoarthritis were found in all patients.

CONCLUSIONS: Combined single bundle ACL reconstruction and ALS reconstruction through a modified single femoral tunnel could significantly improve knee function and stability with low related risk in patients with high risk of failure in ACL injury.}, } @article {pmid39487710, year = {2025}, author = {van Veenhuijzen, K and Tan, HHG and Nitert, AD and van Es, MA and Veldink, JH and van den Berg, LH and Westeneng, HJ}, title = {Longitudinal Magnetic Resonance Imaging in Asymptomatic C9orf72 Mutation Carriers Distinguishes Phenoconverters to Amyotrophic Lateral Sclerosis or Amyotrophic Lateral Sclerosis With Frontotemporal Dementia.}, journal = {Annals of neurology}, volume = {97}, number = {2}, pages = {281-295}, pmid = {39487710}, issn = {1531-8249}, support = {//Stichting ALS Nederland/ ; 772376-EScORIAL//Horizon 2020 Framework Programme/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/diagnostic imaging/pathology ; *C9orf72 Protein/genetics ; *Frontotemporal Dementia/genetics/diagnostic imaging/pathology ; Male ; Female ; Magnetic Resonance Imaging ; Middle Aged ; Longitudinal Studies ; Aged ; Mutation/genetics ; Adult ; Heterozygote ; Atrophy ; Prospective Studies ; Brain/diagnostic imaging/pathology ; }, abstract = {OBJECTIVE: We prospectively studied asymptomatic C9orf72 mutation carriers, identifying those developing amyotrophic lateral sclerosis (ALS) or frontotemporal dementia (FTD).

METHODS: We enrolled 56 asymptomatic family members (AFM) with a C9orf72 mutation (AFM C9+), 132 non-carriers (AFM C9-), and 359 population-based controls. Using 3 T magnetic resonance imaging, we measured cortical thickness, gyrification, and subcortical volumes longitudinally. Linear mixed-effects models on non-converting AFM C9+ scans (n = 107) created a reference for these measurements, establishing individual atrophy patterns. Atrophy patterns from presymptomatic phenoconverters (n = 10 scans) served as a template for group comparisons and similarity assessments. Similarity with phenoconverters was quantified using Dice similarity coefficient (DSC) for cortical and Kullback-Leibler similarity (KLS) for subcortical measures. Using longitudinal similarity assessments, we predicted when participants would reach the average similarity level of phenoconverters at their first post-onset scan.

RESULTS: Five AFM C9+ converted to ALS or ALS-FTD. Up to 6 years before symptoms, these phenoconverters exhibited significant atrophy in frontal, temporal, parietal, and cingulate cortex, along with smaller thalamus, hippocampus, and amygdala compared to other AFM C9+. Some non-converted AFM C9+ had high DSC and KLS, approaching values of phenoconverters, whereas others, along with AFM C9- and controls, had lower values. At age 80, we predicted 27.9% (95% confidence interval, 13.2-40.1%) of AFM C9+ and no AFM C9- would reach the same DSC as phenoconverters.

INTERPRETATION: Distinctive atrophy patterns are visible years before symptom onset on presymptomatic scans of phenoconverters. Combining baseline and follow-up similarity measures may serve as a promising imaging biomarker for identifying those at risk of ALS or ALS-FTD. ANN NEUROL 2025;97:281-295.}, } @article {pmid39487328, year = {2024}, author = {Paganoni, S and Harkey, B and Giacomelli, E and Cudkowicz, M and , }, title = {Lessons from the HEALEY adaptive platform trial in amyotrophic lateral sclerosis.}, journal = {Nature aging}, volume = {4}, number = {11}, pages = {1512-1515}, pmid = {39487328}, issn = {2662-8465}, } @article {pmid39486621, year = {2024}, author = {Stephani, C and Krämer, H and Chakalov, I and Bähr, M and Paulus, W and Antal, A and Koch, JC}, title = {Static transcranial magnetic stimulation does not alter cortical excitability in patients with amyotrophic lateral sclerosis on riluzole.}, journal = {Brain stimulation}, volume = {17}, number = {6}, pages = {1244-1246}, doi = {10.1016/j.brs.2024.10.013}, pmid = {39486621}, issn = {1876-4754}, } @article {pmid39486473, year = {2024}, author = {Wang, HE and Daya, MR and Schmicker, R and Nassal, M and Okubo, M and Aramendi, E and Alonso, E and Idris, A and Panchal, AR and Jaureguibeitia, X and Aufderheide, T and Carlson, J and Nichol, G}, title = {Vasopressor or advanced airway first in cardiac arrest?.}, journal = {Resuscitation}, volume = {205}, number = {}, pages = {110422}, pmid = {39486473}, issn = {1873-1570}, support = {K08 HL168330/HL/NHLBI NIH HHS/United States ; UH2 HL125163/HL/NHLBI NIH HHS/United States ; UH3 HL125163/HL/NHLBI NIH HHS/United States ; }, mesh = {Aged ; Female ; Humans ; Male ; Middle Aged ; *Airway Management/methods ; *Cardiopulmonary Resuscitation/methods ; Epinephrine/administration & dosage ; Intubation, Intratracheal/methods ; *Out-of-Hospital Cardiac Arrest/therapy/mortality ; Return of Spontaneous Circulation ; *Vasoconstrictor Agents/therapeutic use/administration & dosage ; Vasopressins/therapeutic use/administration & dosage ; }, abstract = {BACKGROUND: While resuscitation guidelines emphasize early vasopressor administration and advanced airway management, their optimal sequence remains unclear. We sought to determine the associations between vasopressor-airway resuscitation sequence and out-of-hospital cardiac arrest (OHCA) outcomes in the Pragmatic Airway Resuscitation Trial (PART).

METHODS: We analyzed data from the PART trial. For each patient we determined times of first vasopressor administration (epinephrine or vasopressin), and successful advanced airway insertion (laryngeal tube or endotracheal tube). We classified each case as vasopressor-first or advanced airway-first. We used Generalized Estimating Equations to determine associations between vasopressor-airway sequence and outcomes (72-hour survival, return of spontaneous circulation (ROSC) on emergency department arrival, survival to hospital discharge, hospital survival with favorable neurologic status) and CPR outside of recommended parameters (chest compression fraction <0.8, chest compression rate <100 or >120 per min, or ventilation rate <8 or >12 breaths/min), adjusting for confounders.

RESULTS: Of 3,004 patients in the parent trial, we analyzed 2,404, including 1,821 vasopressor-first and 583 advanced airway-first. Median intervention times: ALS arrival-to-vasopressor 8 min (IQR 6-11) and ALS arrival-to-airway 11 min (8-15). Compared with airway-first, vasopressor-first sequence was not associated with 72-hour survival (adjusted OR 0.96; 95% CI: 0.71-1.31), ROSC (0.83; 0.66-1.06), hospital survival (1.09; 0.68-1.73), or hospital survival with favorable neurologic status (0.97; 0.53-1.78). Vasopressor-first sequence was not associated with non-compliance with recommended CPR performance parameters.

CONCLUSIONS: Vasopressor-airway resuscitation sequence was not associated with OHCA outcomes or CPR quality.}, } @article {pmid39486415, year = {2024}, author = {Al-Azzam, N and To, JH and Gautam, V and Street, LA and Nguyen, CB and Naritomi, JT and Lam, DC and Madrigal, AA and Lee, B and Jin, W and Avina, A and Mizrahi, O and Mueller, JR and Ford, W and Schiavon, CR and Rebollo, E and Vu, AQ and Blue, SM and Madakamutil, YL and Manor, U and Rothstein, JD and Coyne, AN and Jovanovic, M and Yeo, GW}, title = {Inhibition of RNA splicing triggers CHMP7 nuclear entry, impacting TDP-43 function and leading to the onset of ALS cellular phenotypes.}, journal = {Neuron}, volume = {112}, number = {24}, pages = {4033-4047.e8}, doi = {10.1016/j.neuron.2024.10.007}, pmid = {39486415}, issn = {1097-4199}, support = {R01 HG012216/HG/NHGRI NIH HHS/United States ; U24 HG009889/HG/NHGRI NIH HHS/United States ; R01 HG004659/HG/NHGRI NIH HHS/United States ; R35 GM128802/GM/NIGMS NIH HHS/United States ; R01 AG071869/AG/NIA NIH HHS/United States ; P30 CA014195/CA/NCI NIH HHS/United States ; }, mesh = {*Amyotrophic Lateral Sclerosis/metabolism/genetics/pathology ; Humans ; *RNA Splicing ; *Motor Neurons/metabolism ; *Induced Pluripotent Stem Cells/metabolism ; *DNA-Binding Proteins/metabolism/genetics ; *RNA-Binding Proteins/metabolism/genetics ; Cell Nucleus/metabolism ; Phenotype ; Active Transport, Cell Nucleus ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is linked to the reduction of certain nucleoporins in neurons. Increased nuclear localization of charged multivesicular body protein 7 (CHMP7), a protein involved in nuclear pore surveillance, has been identified as a key factor damaging nuclear pores and disrupting transport. Using CRISPR-based microRaft, followed by gRNA identification (CRaft-ID), we discovered 55 RNA-binding proteins (RBPs) that influence CHMP7 localization, including SmD1, a survival of motor neuron (SMN) complex component. Immunoprecipitation-mass spectrometry (IP-MS) and enhanced crosslinking and immunoprecipitation (CLIP) analyses revealed CHMP7's interactions with SmD1, small nuclear RNAs, and splicing factor mRNAs in motor neurons (MNs). ALS induced pluripotent stem cell (iPSC)-MNs show reduced SmD1 expression, and inhibiting SmD1/SMN complex increased CHMP7 nuclear localization. Crucially, overexpressing SmD1 in ALS iPSC-MNs restored CHMP7's cytoplasmic localization and corrected STMN2 splicing. Our findings suggest that early ALS pathogenesis is driven by SMN complex dysregulation.}, } @article {pmid39478664, year = {2025}, author = {Ropert, B and Bannwarth, S and Genin, EC and Vaillant-Beuchot, L and Lacas-Gervais, S and Madji Hounoum, B and Bernardin, A and Dinh, N and Mauri-Crouzet, A and D'Elia, MA and Augé, G and Lespinasse, F and Di Giorgio, A and Meira, W and Bonnefoy, N and Monassier, L and Schiff, M and Sago, L and Kilinc, D and Brau, F and Redeker, V and Bohl, D and Tribouillard-Tanvier, D and Procaccio, V and Azoulay, S and Ricci, JE and Delahodde, A and Paquis-Flucklinger, V}, title = {Nifuroxazide rescues the deleterious effects due to CHCHD10-associated MICOS defects in disease models.}, journal = {Brain : a journal of neurology}, volume = {148}, number = {5}, pages = {1665-1679}, doi = {10.1093/brain/awae348}, pmid = {39478664}, issn = {1460-2156}, support = {ANR-16-CE16-0024-01//Agence Nationale de la Recherche/ ; //Association Française contre les Myopathies/ ; //la Ligue Nationale contre le Cancer/ ; //la ville de Nice/ ; FDT202012010694//Fondation pour la Recherche Médicale/ ; MND202004011475//Fondation pour la Recherche Médicale/ ; P-21-03626//French RENATECH network/ ; }, mesh = {Humans ; *Mitochondrial Proteins/genetics/metabolism ; *Hydroxybenzoates/pharmacology ; *Mitochondria/drug effects/metabolism ; Motor Neurons/drug effects/metabolism ; Fibroblasts/drug effects/metabolism ; Induced Pluripotent Stem Cells/drug effects ; Mitochondria Associated Membranes ; Nitrofurans ; }, abstract = {The identification of a point mutation (p.Ser59Leu) in the CHCHD10 gene was the first genetic evidence that mitochondrial dysfunction can trigger motor neuron disease. Since then, we have shown that this mutation leads to the disorganization of the MItochondrial contact site and Cristae Organizing System (MICOS) complex that maintains the mitochondrial cristae structure. Here, we generated yeast mutant strains mimicking MICOS instability and used them to test the ability of more than 1600 compounds from two repurposed libraries to rescue the growth defect of those cells. Among the hits identified, we selected nifuroxazide, a broad-spectrum antibacterial molecule. We show that nifuroxazide rescues mitochondrial network fragmentation and cristae abnormalities in CHCHD10S59L/+ patient fibroblasts. This molecule also decreases caspase-dependent death of human CHCHD10S59L/+ induced pluripotent stem cell-derived motor neurons. Its benefits involve KIF5B-mediated mitochondrial transport enhancement, evidenced by increased axonal movement and syntaphilin degradation in patient-derived motor neurons. Our findings strengthen the MICOS-mitochondrial transport connection. Nifuroxazide and analogues emerge as potential therapeutics for MICOS-related disorders like motor neuron disease. Its impact on syntaphilin hints at broader neurological disorder applicability for nifuroxazide.}, } @article {pmid39478194, year = {2024}, author = {Yang, M and You, D and Liu, G and Lu, Y and Yang, G and O'Brien, T and Henshall, DC and Hardiman, O and Cai, L and Liu, M and Shen, S}, title = {Polyethyleneimine facilitates the growth and electrophysiological characterization of iPSC-derived motor neurons.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {26106}, pmid = {39478194}, issn = {2045-2322}, support = {16/RC/3948/SFI_/Science Foundation Ireland/Ireland ; C2024205026//Natural Science Foundation of Hebei Province/ ; L2024B36//Doctoral Research Initiation Fund Project of Hebei Normal University/ ; GJHZ20200731095005016//International Scientific and Technological Cooperation Foundation of Shenzhen/ ; 00000326//Medical-Engineering Interdisciplinary Research Foundation of ShenZhen University/ ; }, mesh = {*Polyethyleneimine/pharmacology ; *Electrophysiology ; *Induced Pluripotent Stem Cells/drug effects ; *Cell Proliferation/drug effects ; Motor Neurons/drug effects ; Amyotrophic Lateral Sclerosis/physiopathology ; Humans ; Cells, Cultured ; Cell Differentiation ; }, abstract = {Induced pluripotent stem cell (iPSC) technology, in combination with electrophysiological characterization via multielectrode array (MEA), has facilitated the utilization of iPSC-derived motor neurons (iPSC-MNs) as highly valuable models for underpinning pathogenic mechanisms and developing novel therapeutic interventions for motor neuron diseases (MNDs). However, the challenge of MN adherence to the MEA plate and the heterogeneity presented in iPSC-derived cultures raise concerns about the reproducibility of the findings obtained from these cellular models. We discovered that one novel factor modulating the electrophysiological activity of iPSC-MNs is the extracellular matrix (ECM) used in the coating to support in vitro growth, differentiation and maturation of iPSC-MNs. The current study showed that two coating conditions, namely, Poly-L-ornithine/Matrigel (POM) and Polyethyleneimine (PEI) strongly promoted attachment of iPSC-MNs on MEA culture dishes compared to three other coating conditions, and both facilitated the maturation of iPSC-MNs as characterized by the detection of extensive electrophysiological activities from the MEA plates. POM coating accelerated the maturation of the iPSC-MNs for up to 5 weeks, which suits modeling of neurodevelopmental disorders. However, the application of PEI resulted in more even distribution of the MNs on the culture dish and reduced variability of electrophysiological signals from the iPSC-MNs in 7-week cultures, which permitted the detection of enhanced excitability in iPSC-MNs from patients with amyotrophic lateral sclerosis (ALS). This study provides a comprehensive comparison of five coating conditions and offers POM and PEI as favorable coatings for in vitro modeling of neurodevelopmental and neurodegenerative disorders, respectively.}, } @article {pmid39475611, year = {2024}, author = {Wang, LQ and Ma, Y and Zhang, MY and Yuan, HY and Li, XN and Xia, W and Zhao, K and Huang, X and Chen, J and Li, D and Zou, L and Wang, Z and Le, W and Liu, C and Liang, Y}, title = {Amyloid fibril structures and ferroptosis activation induced by ALS-causing SOD1 mutations.}, journal = {Science advances}, volume = {10}, number = {44}, pages = {eado8499}, pmid = {39475611}, issn = {2375-2548}, mesh = {*Superoxide Dismutase-1/genetics/metabolism/chemistry ; *Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology ; Humans ; *Amyloid/metabolism ; *Mutation ; *Ferroptosis/genetics ; Cryoelectron Microscopy ; Models, Molecular ; Mitochondria/metabolism ; }, abstract = {Over 200 genetic mutations in copper-zinc superoxide dismutase (SOD1) have been linked to amyotrophic lateral sclerosis (ALS). Among these, two ALS-causing mutants, histidine-46→arginine (H46R) and glycine-85→arginine (G85R), exhibit a decreased capacity to bind metal ions. Here, we report two cryo-electron microscopy structures of amyloid fibrils formed by H46R and G85R. These mutations lead to the formation of amyloid fibrils with unique structures distinct from those of the native fibril. The core of these fibrils features a serpentine arrangement with seven or eight β strands, secured by a hydrophobic cavity and a salt bridge between arginine-85 and aspartic acid-101 in the G85R fibril. We demonstrate that these mutant fibrils are notably more toxic and capable of promoting the aggregation of wild-type SOD1 more effectively, causing mitochondrial impairment and activating ferroptosis in cell cultures, compared to wild-type SOD1 fibrils. Our study provides insights into the structural mechanisms by which SOD1 mutants aggregate and induce cytotoxicity in ALS.}, } @article {pmid39475283, year = {2025}, author = {Ziser, L and van Eijk, RPA and Kiernan, MC and McRae, A and Henderson, RD and Schultz, D and Needham, M and Mathers, S and McCombe, P and Talman, P and Vucic, S}, title = {Amyotrophic lateral sclerosis established as a multistep process across phenotypes.}, journal = {European journal of neurology}, volume = {32}, number = {1}, pages = {e16532}, pmid = {39475283}, issn = {1468-1331}, support = {//National Health and Medical Research Council/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/epidemiology ; Middle Aged ; *Phenotype ; Male ; Female ; Aged ; *Registries ; *Age of Onset ; Australia/epidemiology ; Disease Progression ; Incidence ; Adult ; }, abstract = {BACKGROUND AND PURPOSE: Given the accepted multistep process of disease causation in amyotrophic lateral sclerosis (ALS), the present study was undertaken to determine the number of steps required for disease onset across each of the ALS phenotypes.

METHODS: Clinical and demographic data were prospectively accumulated using the Australian Motor Neurone Disease Registry (2005-2016), and age-specific incidence rates were calculated. Poisson regression was utilized to assess the relationship between log age-specific incidence and log age of onset, with McFadden's R[2] used to assess the goodness of fit of the model.

RESULTS: In total, 2647 ALS patients were included, with mean disease-onset age being 62.2 ± 12.1 years. A linear relationship between log incidence and log age was established across ALS phenotypes, with variable slope estimates: bulbar 5.1 (95% confidence interval [CI] 4.6-5.6); cervical 2.7 (95% CI 2.3-3.0); lumbar 3.5 (95% CI 3.2-3.9); flail arm 4.7 (95% CI 3.9-5.5); flail leg 3.6 (95% CI 2.6-4.5); primary lateral sclerosis 2.7 (95% CI 1.8-3.7). Slope estimates were significantly higher in the bulbar compared to the cervical, lumbar and primary lateral sclerosis phenotypes. McFadden's R[2] values were >0.4 for all phenotypes indicating excellent model fit.

DISCUSSION: A multistep process has been established across all ALS phenotypes with variable slope estimates, suggesting that the number of steps to develop disease is different across clinical presentations. Identification of mechanisms underlying slope estimate variability could exert pathophysiological significance.}, } @article {pmid39475135, year = {2024}, author = {Jackowski, T and Horodnicka-Józwa, A and Berus, E and Walczak, M and Petriczko, E}, title = {An analysis of acid-labile subunit (ALS) levels in children with short stature born with normal weight.}, journal = {Endokrynologia Polska}, volume = {75}, number = {5}, pages = {548-557}, doi = {10.5603/ep.100285}, pmid = {39475135}, issn = {2299-8306}, mesh = {Humans ; Child ; Female ; Male ; *Glycoproteins ; Growth Disorders/diagnosis ; Carrier Proteins ; Child, Preschool ; Insulin-Like Growth Factor I/metabolism/analysis ; Insulin-Like Growth Factor Binding Protein 3/blood ; Body Height ; }, abstract = {INTRODUCTION: The acid-labile subunit (ALS) is a protein best known for its function in stabilising the insulin like growth factor-1/2-insulin-like growth factor-1 binding protein 3/5 (IGF-1/2-IGFBP3/5) binary complex by creating the ternary complex and in consequence regulating the biological activity of IGF-1. The aim of the study was to assess ALS concentrations in a chosen population of children with short stature taking into account their clinical diagnosis.

MATERIAL AND METHODS: A total of 109 prepubertal children were involved in the study - 85 children in the study group and 24 in controls. In all the children IGF-1, IGFBP3, and ALS were measured. The study group was divided according to diagnosis into groups: growth hormone deficiency (GHD), constitutional delay of growth and puberty (CDGP), idiopathic short stature (ISS), and familial short stature (FSS).

RESULTS: In the control group the ALS concentration ranged from 4.81 to 13.66 μg/mL. In the whole study group the ALS concentration ranged from 2.73 to 15.81 μg/mL. The difference between both groups was statistically significant (p < 0.0001, R = 0.39). A strong, statistically significant correlation between ALS levels and age was observed, but only in the study group (p < 0.0001, r = 0.59). The ALS standard deviation score (SDS) was not significantly different between the control and CDGP children (p = 0.0644). The ALS concentration was significantly lower in children with short stature. There was, however, no difference between the subgroups of the study group.

CONCLUSION: There was no significant difference in ALS SDS between the control group and children with constitutional delay of growth and development. The usefulness of ALS in routine short stature diagnostics is uncertain, but it might play a role in the diagnosis of children with ISS and CDGP in the future.}, } @article {pmid39474398, year = {2024}, author = {Goyal, O and Goyal, MK}, title = {Critical analysis of the effects of proton pump inhibitors on inflammatory bowel disease: An updated review.}, journal = {World journal of gastroenterology}, volume = {30}, number = {37}, pages = {4160-4162}, pmid = {39474398}, issn = {2219-2840}, mesh = {Humans ; *Colitis, Ulcerative/drug therapy/immunology/diagnosis ; *Crohn Disease/diagnosis/drug therapy/immunology ; *Proton Pump Inhibitors/therapeutic use/adverse effects ; Treatment Outcome ; Review Literature as Topic ; }, abstract = {This letter critically evaluates the effects of proton pump inhibitors (PPIs) on inflammatory bowel disease, particularly focusing on Crohn's disease (CD) and ulcerative colitis (UC), as discussed in Liang et al's recent review. While the review provides significant insights, it relies heavily on cross-sectional and observational studies, which limits the ability to draw causal inferences. The heterogeneous study populations and inconsistent definitions of long-term PPI use further complicate the findings. This letter also highlights the need for rigorous control of confounding factors and considers the potential publication bias in the existing literature. The implications of these issues are discussed in the context of both CD and UC, and future research directions are proposed to address these shortcomings.}, } @article {pmid39474168, year = {2024}, author = {Sandler, AB and Wells, ME and Tran, C and Arakawa, R and Klahs, KJ and Scanaliato, JP and Green, CK and Hettrich, CM and Dunn, JC and Adler, A and Parnes, N}, title = {High rates of return to sport after suprascapular nerve decompression: an updated systematic review.}, journal = {JSES reviews, reports, and techniques}, volume = {4}, number = {4}, pages = {654-661}, pmid = {39474168}, issn = {2666-6391}, abstract = {BACKGROUND: Suprascapular nerve decompression (SSND) remains a controversial procedure. In 2018, Momaya et al published the first systematic review of SSND noting satisfactory outcomes with low rates of complications; however, numerous studies published since have noted no benefit in routinely adding SSND to other arthroscopic surgeries, contributing to existing contention regarding the procedure. The purpose of this study is to provide an updated assessment of outcomes after SSND.

METHODS: To conduct this updated systematic review, a search of PubMed (MEDLINE) for relevant studies published prior to January 21, 2023 was conducted. Outcomes including patient-reported clinical outcomes, return to sport, preoperative and postoperative electrodiagnostic testing, and adverse events were collected and pooled for assessment. Studies were eligible for inclusion if they met Momaya et al's inclusion criteria and/or reported outcomes following SSND at either the suprascapular notch or spinoglenoid notch.

RESULTS: In total, 730 patients from 33 studies were eligible for inclusion. All patient-reported outcome measure scores including American Shoulder Elbow Surgeon Standardized Shoulder Assessment; Constant-Murley score; Disabilities of the Arm, Shoulder, and Hand; Subjective Shoulder Value; University of California-Los Angeles shoulder; and visual analog scale pain scores improved significantly postoperatively, with improvements ranging from 53.5% to 102.6% of preoperative values. Ultimately, 98% (n = 90/92) of patients returned to sport or military duty and 96% of these patients returned at their previous level of activity (n = 48/50) without heterogeneity among rates between studies (P = .176, P = .238, respectively). Preoperative electrodiagnostic testing was conducted in 93% of patients, and 90% had associated abnormal findings. Continued symptoms were noted among 12% of patients (n = 39/322) with significantly different rates observed between studies. Complications from operative management not limited to SSND occurred in 11% of patients (n = 64/576) and reoperations occurred in 3.3% of patients (n = 15/455).

CONCLUSION: Suprascapular neuropathy treated with SSND significantly improves patient-reported outcomes and is noninferior to similar procedures without SSND. Appropriate clinical diagnosis of suprascapular neuropathy is required as opposed to a routine adjunct procedure with other arthroscopic shoulder surgery. Ultimately, SSND is associated with high rates of return to sport and relatively low rates of adverse events; however, the risk of continued symptoms and electrodiagnostic test-related complications is an important point on preoperative counseling.}, } @article {pmid39473991, year = {2024}, author = {Hobro, AJ and Sakaguchi, T and Akira, S and Smith, NI}, title = {Correlative Quantitative Raman Chemical Imaging and MCR-ALS in Mouse NASH Model Reveals Direct Relationships between Diet and Resultant Liver Pathology.}, journal = {Chemical & biomedical imaging}, volume = {2}, number = {8}, pages = {577-583}, pmid = {39473991}, issn = {2832-3637}, abstract = {Raman imaging has the capability to provide unlabeled, spatially aware analysis of chemical components, with no a priori assumptions. Several lifestyle diseases such as nonalcoholic steatohepatitis (NASH) can appear in the liver as changes in the nature, abundance, and distribution of lipids, proteins, and other biomolecules and are detectable by Raman imaging. In order to identify which of these liver-associated changes occur as a direct result of the diet and which are secondary effects, we developed correlative imaging and analysis of diet and liver samples. Oleic acid was found to be a direct contributor to NASH liver composition, whereas protein and collagen distributions were found to be affected in a manner consistent with early fibrotic transformation, as a secondary consequence of the high-fat diet.}, } @article {pmid39473807, year = {2024}, author = {Oliveira, GC and Ngo, QC and Passos, LA and Oliveira, LS and Stylianou, S and Papa, JP and Kumar, D}, title = {Video Assessment to Detect Amyotrophic Lateral Sclerosis.}, journal = {Digital biomarkers}, volume = {8}, number = {1}, pages = {171-180}, pmid = {39473807}, issn = {2504-110X}, abstract = {INTRODUCTION: Weakened facial movements are early-stage symptoms of amyotrophic lateral sclerosis (ALS). ALS is generally detected based on changes in facial expressions, but large differences between individuals can lead to subjectivity in the diagnosis. We have proposed a computerized analysis of facial expression videos to detect ALS.

METHODS: This study investigated the action units obtained from facial expression videos to differentiate between ALS patients and healthy individuals, identifying the specific action units and facial expressions that give the best results. We utilized the Toronto NeuroFace Dataset, which includes nine facial expression tasks for healthy individuals and ALS patients.

RESULTS: The best classification accuracy was 0.91 obtained for the pretending to smile with tight lips expression.

CONCLUSION: This pilot study shows the potential of using computerized facial expression analysis based on action units to identify facial weakness symptoms in ALS.}, } @article {pmid39473490, year = {2024}, author = {Fei, Y and Ding, Y}, title = {The role of ferroptosis in neurodegenerative diseases.}, journal = {Frontiers in cellular neuroscience}, volume = {18}, number = {}, pages = {1475934}, pmid = {39473490}, issn = {1662-5102}, abstract = {Ferroptosis represents an iron[-] and lipid peroxidation (LPO)-mediated form of regulated cell death (RCD). Recent evidence strongly suggests the involvement of ferroptosis in various neurodegenerative diseases (NDs), particularly Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS), among others. The treatment of ferroptosis poses both opportunities and challenges in the context of ND. This review provides a comprehensive overview of characteristic features, induction and inhibition of ferroptosis, highlighting the ferroptosis inhibitor and the underlying mechanisms responsible for its occurrence. Moreover, the review explores how these mechanisms contribute to the pathogenesis and progression of major neurodegenerative disorders. Additionally, it presents novel insights into the role of ferroptosis in ND and summarizes recent advancements in the development of therapeutic approaches targeting ferroptosis. These insights and advancements hold potential to guide future strategies aimed at effectively managing these debilitating medical conditions.}, } @article {pmid39473462, year = {2024}, author = {Zhang, Y and Xu, N and Yan, C and Zhou, X and Qiao, Q and Miao, L and Xu, Z}, title = {Live-Cell Imaging to Resolve Salt-Induced Liquid-Liquid Phase Separation of FUS Protein by Dye Self-Labeling.}, journal = {Chemical & biomedical imaging}, volume = {2}, number = {1}, pages = {70-80}, pmid = {39473462}, issn = {2832-3637}, abstract = {The aggregation of fusion in sarcoma (FUS) in the cytoplasm and nucleus is a pathological feature of Amyotrophic lateral sclerosis (ALS) and Frontotemporal Dementia (FTD). Genetic mutations, abnormal protein synthesis, environmental stress, and aging have all been implicated as causative factors in this process. Salt ions are essential to many physiological processes in the body, and the imbalance of them is an important environmental stress factor in cells. However, their effect on liquid-liquid phase separation (LLPS) of FUS proteins in living cells is not well understood. Here, we map the various salt-induced LLPS of FUS in living cells by genetically coding and self-labeling FUS with organic dyes. The brightness and photostability of the dyes enable long-term imaging to track the mechanism of the assembly and disappearance of FUS phase separation. The FUS protein showed a better phase separation tendency under 0.3 M salt stimulation, and there was a large amount of FUS shuttling from the nucleus to the cytoplasm. At this concentration, various salt solutions displayed different effects on the phase separation of FUS protein, following the Hofmeister effects. We further observed that the assembly of FUS droplets underwent a process of rapid formation of small droplets, plateaus, and mutual fusion. Strikingly, The CsCl-stimulated FUS droplets were not completely reversible after washing, and some solid-like granules remained in the nucleus. Taken together, these results help broaden our understanding of the LLPS of FUS proteins in cellular stress responses.}, } @article {pmid39473221, year = {2024}, author = {Ito, D and Okada, K}, title = {Rethinking antisense oligonucleotide therapeutics for amyotrophic lateral sclerosis.}, journal = {Annals of clinical and translational neurology}, volume = {11}, number = {12}, pages = {3054-3063}, pmid = {39473221}, issn = {2328-9503}, support = {21H02812//Ministry of Education, Culture, Sports, Science and Technology of Japan/ ; }, mesh = {Animals ; Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/genetics/therapy ; *Oligonucleotides, Antisense/administration & dosage/genetics ; Superoxide Dismutase-1/genetics ; }, abstract = {Antisense oligonucleotides, which are used to silence target genes, are gaining attention as a novel drug discovery modality for proteinopathies. However, while clinical trials for neurodegenerative diseases like amyotrophic lateral sclerosis have been conducted in recent years, the results have not always been favorable. The results from a Phase III trial of the antisense oligonucleotide, that is, tofersen, which targets SOD1 mRNA, showed decreased levels of cerebrospinal fluid SOD1 and plasma neurofilament light chain but no improvements in primary clinical endpoint. Moreover, case reports pertaining to patients with amyotrophic lateral sclerosis carrying FUS and C9orf72 mutations who received antisense oligonucleotide-based treatments have demonstrated a notable reduction in the targeted protein (thus providing the proof of mechanism) but with no discernible clinical benefits. There are several possible reasons why antisense oligonucleotides knockdown fails to achieve proof of concept, which need to be addressed: on-target adverse effects resulting from the loss of function of target gene and irreversible neuronal death cascade due to toxic protein accumulation, among other factors. This review provides an overview of the current status and discusses the prospects of antisense oligonucleotides treatment for amyotrophic lateral sclerosis.}, } @article {pmid39472924, year = {2024}, author = {Stikvoort García, DJL and Sleutjes, BTHM and Mugge, W and Plouvier, JJ and Goedee, HS and Schouten, AC and van der Helm, FCT and van den Berg, LH}, title = {Instrumented assessment of lower and upper motor neuron signs in amyotrophic lateral sclerosis using robotic manipulation: an explorative study.}, journal = {Journal of neuroengineering and rehabilitation}, volume = {21}, number = {1}, pages = {193}, pmid = {39472924}, issn = {1743-0003}, support = {AV20180012//Stichting ALS Nederland/ ; AV20180012//Stichting ALS Nederland/ ; AV20180012//Stichting ALS Nederland/ ; AV20180012//Stichting ALS Nederland/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology/diagnosis ; Male ; Middle Aged ; Female ; *Robotics/instrumentation/methods ; *Electromyography/methods/instrumentation ; Aged ; *Motor Neurons/physiology ; *Muscle, Skeletal/physiopathology/physiology ; Torque ; Wrist Joint/physiopathology ; Adult ; Muscle Strength/physiology ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a lethal progressive neurodegenerative disease characterized by upper motor neuron (UMN) and lower motor neuron (LMN) involvement. Their varying degree of involvement results in a clinical heterogenous picture, making clinical assessments of UMN signs in patients with ALS often challenging. We therefore explored whether instrumented assessment using robotic manipulation could potentially be a valuable tool to study signs of UMN involvement.

METHODS: We examined the dynamics of the wrist joint of 15 patients with ALS and 15 healthy controls using a Wristalyzer single-axis robotic manipulator and electromyography (EMG) recordings in the flexor and extensor muscles in the forearm. Multi-sinusoidal torque perturbations were applied, during which participants were asked to either relax, comply or resist. A neuromuscular model was used to study muscle viscoelasticity, e.g. stiffness (k) and viscosity (b), and reflexive properties, such as velocity, position and force feedback gains (kv, kp and kf, respectively) that dominated the responses. We further obtained clinical signs of LMN (muscle strength) and UMN (e.g. reflexes, spasticity) dysfunction, and evaluated their relation with the estimated neuromuscular model parameters.

RESULTS: Only force feedback gains (kf) were elevated in patients (p = 0.033) compared to controls. Higher kf, as well as the resulting reflexive torque (Tref), were both associated with more severe UMN dysfunction in the examined arm (p = 0.040 and p < 0.001). Patients with UMN symptoms in the examined arm had increased kf and Tref compared to controls (both p = 0.037). Neither of these measures was related to muscle strength, but muscle stiffness (k) was lower in weaker patients (p = 0.012). All these findings were obtained from the relaxed test. No differences were observed during the instructions comply and resist.

CONCLUSIONS: This findings are proof-of-concept that instrumented assessment using robotic manipulation is a feasible technique in ALS, which may provide quantitative, operator-independent measures relating to UMN symptoms. Elevated force feedback gains, driving larger reflexive muscle torques, appear to be particularly indicative of clinically established levels of UMN dysfunction in the examined arm.}, } @article {pmid39472842, year = {2024}, author = {Guazzo, A and Atzeni, M and Idi, E and Trescato, I and Tavazzi, E and Longato, E and Manera, U and Chió, A and Gromicho, M and Alves, I and de Carvalho, M and Vettoretti, M and Di Camillo, B}, title = {Predicting clinical events characterizing the progression of amyotrophic lateral sclerosis via machine learning approaches using routine visits data: a feasibility study.}, journal = {BMC medical informatics and decision making}, volume = {24}, number = {Suppl 4}, pages = {318}, pmid = {39472842}, issn = {1472-6947}, support = {GA01017598//HORIZON EUROPE Health/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/therapy ; Humans ; *Feasibility Studies ; *Disease Progression ; *Machine Learning ; Male ; Middle Aged ; Female ; Aged ; Prognosis ; Noninvasive Ventilation ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that results in death within a short time span (3-5 years). One of the major challenges in treating ALS is its highly heterogeneous disease progression and the lack of effective prognostic tools to forecast it. The main aim of this study was, then, to test the feasibility of predicting relevant clinical outcomes that characterize the progression of ALS with a two-year prediction horizon via artificial intelligence techniques using routine visits data.

METHODS: Three classification problems were considered: predicting death (binary problem), predicting death or percutaneous endoscopic gastrostomy (PEG) (multiclass problem), and predicting death or non-invasive ventilation (NIV) (multiclass problem). Two supervised learning models, a logistic regression (LR) and a deep learning multilayer perceptron (MLP), were trained ensuring technical robustness and reproducibility. Moreover, to provide insights into model explainability and result interpretability, model coefficients for LR and Shapley values for both LR and MLP were considered to characterize the relationship between each variable and the outcome.

RESULTS: On the one hand, predicting death was successful as both models yielded F1 scores and accuracy well above 0.7. The model explainability analysis performed for this outcome allowed for the understanding of how different methodological approaches consider the input variables when performing the prediction. On the other hand, predicting death alongside PEG or NIV proved to be much more challenging (F1 scores and accuracy in the 0.4-0.6 interval).

CONCLUSIONS: In conclusion, predicting death due to ALS proved to be feasible. However, predicting PEG or NIV in a multiclass fashion proved to be unfeasible with these data, regardless of the complexity of the methodological approach. The observed results suggest a potential ceiling on the amount of information extractable from the database, e.g., due to the intrinsic difficulty of the prediction tasks at hand, or to the absence of crucial predictors that are, however, not currently collected during routine practice.}, } @article {pmid39472796, year = {2024}, author = {Zheng, K and Chen, M and Xu, X and Li, P and Yin, C and Wang, J and Liu, B}, title = {Chemokine CXCL13-CXCR5 signaling in neuroinflammation and pathogenesis of chronic pain and neurological diseases.}, journal = {Cellular & molecular biology letters}, volume = {29}, number = {1}, pages = {134}, pmid = {39472796}, issn = {1689-1392}, support = {82474625//National Natural Science Foundation of China/ ; 82305368//National Natural Science Foundation of China/ ; }, mesh = {Humans ; *Chemokine CXCL13/metabolism/genetics ; *Chronic Pain/metabolism/immunology ; *Receptors, CXCR5/metabolism ; *Signal Transduction ; *Nervous System Diseases/metabolism ; Animals ; *Neuroinflammatory Diseases/metabolism ; }, abstract = {Chronic pain dramatically affects life qualities of the sufferers. It has posed a heavy burden to both patients and the health care system. However, the current treatments for chronic pain are usually insufficient and cause many unwanted side effects. Chemokine C-X-C motif ligand 13 (CXCL13), formerly recognized as a B cell chemokine, binds with the cognate receptor CXCR5, a G-protein-coupled receptor (GPCR), to participate in immune cell recruitments and immune modulations. Recent studies further demonstrated that CXCL13-CXCR5 signaling is implicated in chronic pain via promoting neuroimmune interaction and neuroinflammation in the sensory system. In addition, some latest work also pointed out the involvement of CXCL13-CXCR5 in the pathogenesis of certain neurological diseases, including ischemic stroke and amyotrophic lateral sclerosis. Therefore, we aim to outline the recent findings in regard to the involvement of CXCL13-CXCR5 signaling in chronic pain as well as certain neurological diseases, with the focus on how this chemokine signaling contributes to the pathogenesis of these neurological diseases via regulating neuroimmune interaction and neuroinflammation. Strategies that can specifically target CXCL13-CXCR5 signaling in distinct locations may provide new therapeutic options for these neurological diseases.}, } @article {pmid39471924, year = {2024}, author = {Xu, Y and Xu, T and Huang, C and Liu, L and Kwame, AW and Zhu, Y and Ren, J}, title = {Preventive intervention with Agaricus blazei murill polysaccharide exerts anti-tumor immune effect on intraperitoneal metastasis colorectal cancer.}, journal = {International journal of biological macromolecules}, volume = {282}, number = {Pt 3}, pages = {136810}, doi = {10.1016/j.ijbiomac.2024.136810}, pmid = {39471924}, issn = {1879-0003}, mesh = {Animals ; *Agaricus/chemistry ; *Colorectal Neoplasms/pathology/immunology/prevention & control/drug therapy ; Mice ; Cell Line, Tumor ; Tumor Microenvironment/drug effects ; Peritoneal Neoplasms/secondary/drug therapy/prevention & control/immunology ; Fungal Polysaccharides/pharmacology/chemistry ; CD8-Positive T-Lymphocytes/drug effects/immunology ; Polysaccharides/pharmacology/chemistry ; Antineoplastic Agents/pharmacology ; }, abstract = {Agaricus blazei murill (ABM) mainly exerts its antitumor effect via modulation of the immune system. However, the immunomodulatory role of the ABM polysaccharide (ABMP) in mice with subcutaneously and intraperitoneally implanted MC38 tumor remains to be explored. This study aimed to define the progression effect of inhibiting tumor of ABMP in subcutaneous and intraperitoneal models and its effect on tumor microenvironment (TME) metabolism. In vitro experiments showed that ABMP could significantly promote the activity of CD8+ T immune cells in the co-culture system and promoted their colorectal cancer killing function (p < 0.05). In vivo animal exploration further showed that ABMP could inhibit the growth of intraperitoneal but not subcutaneous tumors. MCR-ALS analysis revealed a significant reduction in the signal of lipid-related spectral components in the TME of peritoneal tumors after ABMP intervention. In addition, preventive intervention with ABMP increased ω-3 polyunsaturated fatty acids content in intraperitoneal TME, revealing that ABMP shifted the metabolic landscape of the TME to promote T cell function and achieved immune regulation. These results suggest that the inhibitory effect of ABMP on colon cancer may be tumor stage-dependent, and that remodeling of fatty acid composition may be an important determinant of its action at any given stage.}, } @article {pmid39471842, year = {2024}, author = {Ferro, F and Wolf, CR and Henstridge, C and Inesta-Vaquera, F}, title = {Novel in vivo TDP-43 stress reporter models to accelerate drug development in ALS.}, journal = {Open biology}, volume = {14}, number = {10}, pages = {240073}, pmid = {39471842}, issn = {2046-2441}, support = {//MND Scotland/ ; //ARUK/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/metabolism/drug therapy/genetics/pathology ; Animals ; Mice ; *DNA-Binding Proteins/metabolism/genetics ; *Disease Models, Animal ; Humans ; *Mice, Transgenic ; *Genes, Reporter ; Oxidative Stress/drug effects ; NF-E2-Related Factor 2/metabolism/genetics ; Drug Development ; DNA Damage ; Biomarkers ; }, abstract = {The development of therapies to combat neurodegenerative diseases is widely recognized as a research priority. Despite recent advances in understanding their molecular basis, there is a lack of suitable early biomarkers to test selected compounds and accelerate their translation to clinical trials. We have investigated the utility of in vivo reporters of cytoprotective pathways (e.g. NRF2, p53) as surrogate early biomarkers of the ALS degenerative disease progression. We hypothesized that cellular stress observed in a model of ALS may precede overt cellular damage and could activate our cytoprotective pathway reporters. To test this hypothesis, we generated novel ALS-reporter mice by crossing the hTDP-43tg model into our oxidative stress/inflammation (Hmox1; NRF2 pathway) and DNA damage (p21; p53 pathway) stress reporter models. Histological analysis of reporter expression in a homozygous hTDP-43tg background demonstrated a time-dependent and tissue-specific activation of the reporters in tissues directly associated with ALS, before moderate clinical signs are observed. Further work is warranted to determine the specific mechanisms by which TDP-43 accumulation leads to reporter activation and whether therapeutic intervention modulates reporters' expression. We anticipate the reporter strategy could be of great value in developing treatments for a range of degenerative disorders.}, } @article {pmid39471269, year = {2024}, author = {Stenson, K and Chew, S and Dong, S and Heithoff, K and Wang, MJ and Rosenfeld, J}, title = {Health care resource utilization and costs across stages of amyotrophic lateral sclerosis in the United States.}, journal = {Journal of managed care & specialty pharmacy}, volume = {30}, number = {11}, pages = {1239-1247}, pmid = {39471269}, issn = {2376-1032}, mesh = {*Amyotrophic Lateral Sclerosis/economics/therapy ; Humans ; United States ; Male ; Female ; Middle Aged ; Aged ; *Patient Acceptance of Health Care/statistics & numerical data ; *Health Care Costs/statistics & numerical data ; Adult ; Health Resources/economics/statistics & numerical data ; Severity of Illness Index ; Retrospective Studies ; Disease Progression ; Cost of Illness ; Databases, Factual ; }, abstract = {BACKGROUND: People living with ALS (plwALS) experience motor control loss, speech/swallowing difficulties, respiratory insufficiency, and early death. Advancing disease stage is typically associated with a greater burden on the health care system, and delays in diagnosis can result in substantial health care resource utilization (HCRU).

OBJECTIVE: To estimate HCRU and cost burden of plwALS across disease stages from a US payer perspective we assessed HCRU and costs in early-, mid-, and late-stage ALS.

METHODS: Using insurance claims data from the IBM MarketScan Databases between January 2013 and December 2019, we identified plwALS as having at least 2 claims at least 27 days apart with an ALS International Classification of Diseases, Ninth or Tenth Revision diagnosis code (335.20/G12.21) or at least 1 ALS diagnosis code and prescription filled for riluzole/edaravone. Eligible plwALS were aged at least 18 years and had at least 12 months of enrollment data before and at least 6 months after the index date (date diagnosis criteria met). plwALS were grouped into disease stages using an ALS severity-based staging algorithm developed using ALS symptom and staging survey data from 142 neurologists reporting on 880 plwALS. The starting date of each severity stage was defined as the first date of an ALS symptom within the early-, mid-, and late-stage categories, respectively. The ending date for a severity stage was defined as the day before the first date of an ALS symptom from a more severe category. plwALS could transition to more severe stages, with reverse transition of severity excluded. Mixed regression modeling was used to assess differences in HCRU and costs per person-year between severity stages, adjusted for age and sex.

RESULTS: 2,273 plwALS were included in the total ALS study sample, with 1,215 early-stage, 1,511 midstage, and 1,186 late-stage plwALS. 90% of early-stage plwALS had ALS symptoms before diagnosis, and 27% of late-stage plwALS had a late-stage symptom before diagnosis. In the evaluation period, later-stage ALS groups had more overall hospital admissions (early = 0.15, middle = 0.23, and late = 0.74; P < 0.01), outpatient visits/service (early = 26.81, middle = 32.78, and late = 48.54; P < 0.01), emergency department visits (early = 0.46, middle = 0.69, and late = 1.03; P < 0.01), and total prescription count (early = 9.23, middle = 11.37, and late = 12.72; P < 0.01) over 12 months. Annualized costs increased as ALS progressed (early = $31,411, middle = $51,481, and late = $121,903; P < 0.01), which was primarily driven by higher frequency of and cost per hospital admission.

CONCLUSIONS: HCRU and costs increased with ALS progression, with diagnosis frequently occurring even after experiencing late-stage symptoms. These findings highlight the potential value of delaying progression into a more resource-intensive stage by diagnosing and adequately treating plwALS earlier in the disease course.}, } @article {pmid39470866, year = {2025}, author = {Liu, Y and Fu, R and Jia, H and Yang, K and Ren, F and Zhou, MS}, title = {GHRH and its analogues in central nervous system diseases.}, journal = {Reviews in endocrine & metabolic disorders}, volume = {26}, number = {3}, pages = {427-442}, pmid = {39470866}, issn = {1573-2606}, support = {82270434//National Natural Science Foundation of China/ ; }, mesh = {Humans ; *Growth Hormone-Releasing Hormone/analogs & derivatives/metabolism/therapeutic use ; Animals ; *Central Nervous System Diseases/metabolism/drug therapy ; Insulin-Like Growth Factor I/metabolism ; }, abstract = {Growth hormone-releasing hormone (GHRH) is primarily produced by the hypothalamus and stimulates the release of growth hormone (GH) in the anterior pituitary gland, which subsequently regulates the production of hepatic insulin-like growth factor-1 (IGF-1). GH and IGF-1 have potent effects on promoting cell proliferation, inhibiting cell apoptosis, as well as regulating cell metabolism. In central nerve system (CNS), GHRH/GH/IGF-1 promote brain development and growth, stimulate neuronal proliferation, and regulate neurotransmitter release, thereby participating in the regulation of various CNS physiological activities. In addition to hypothalamus-pituitary gland, GHRH and GHRH receptor (GHRH-R) are also expressed in other brain cells or tissues, such as endogenous neural stem cells (NSCs) and tumor cells. Alternations in GHRH/GH/IGF-1 axis are associated with various CNS diseases, for example, Alzheimer's disease, amyotrophic lateral sclerosis and emotional disorders manifest GHRH, GH or IGF-1 deficiency, and GH or IGF-1 supplementation exerts beneficial therapeutic effects on these diseases. CNS tumors, such as glioma, can express GHRH and GHRH-R, and activating this signaling pathway promotes tumor cell growth. The synthesized GHRH antagonists have shown to inhibit glioma cell growth and may hold promising as an adjuvant therapy for treating glioma. In addition, we have shown that GHRH agonist MR-409 can improve neurological sequelae after ischemic stroke by activating extrapituitary GHRH-R signaling and promoting endogenous NSCs-derived neuronal regeneration. This article reviews the involvement of GHRH/GH/IGF-1 in CNS diseases, and potential roles of GHRH agonists and antagonists in treating CNS diseases.}, } @article {pmid39470847, year = {2025}, author = {Jellinger, KA}, title = {Mild cognitive impairment in amyotrophic lateral sclerosis: current view.}, journal = {Journal of neural transmission (Vienna, Austria : 1996)}, volume = {132}, number = {3}, pages = {357-368}, pmid = {39470847}, issn = {1435-1463}, support = {Society for the Promotion of Research in Experimental Neurology, Vienna, Austria//Society for the Promotion of Research in Experimental Neurology, Vienna, Austria/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/complications ; *Cognitive Dysfunction/etiology/diagnosis ; *Brain/pathology ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal multi-system neurodegenerative disorder with no effective treatment or cure. Although primarily characterized by motor degeneration, cognitive dysfunction is an important non-motor symptom that has a negative impact on patient and caregiver burden. Mild cognitive deficits are present in a subgroup of non-demented patients with ALS, often preceding motor symptoms. Detailed neuropsychological assessments reveal deficits in a variety of cognitive domains, including those of verbal fluency and retrieval, language, executive function, attention and verbal memory. Mild cognitive impairment (MCI), a risk factor for developing dementia, affects between 10% and over 50% of ALS patients. Neuroimaging revealed atrophy of frontal and temporal cortices, disordered white matter Integrity, volume reduction in amygdala and thalamus, hypometabolism in the frontal and superior temporal gyrus and anterior insula. Neuronal loss in non-motor brain areas, associated with TDP-43 deposition, one of the morphological hallmarks of ALS, is linked to functional disruption of frontostriatal and frontotemporo-limbic connectivities as markers for cognitive deficits in ALS, the pathogenesis of which is still poorly understood. Early diagnosis by increased cerebrospinal fluid or serum levels of neurofilament light/heavy chain or glial fibrillary acidic protein awaits confirmation for MCI in ALS. These fluid biomarkers and early detection of brain connectivity signatures before structural changes will be helpful not only in establishing early premature diagnosis but also in clarifying the pathophysiological mechanisms of MCI in ALS, which might serve as novel targets for prohibition/delay and future adequate treatment of this debilitating disorder.}, } @article {pmid39470585, year = {2024}, author = {Lin, W and Wu, X and Ou, G}, title = {Causal association of circulating inflammatory proteins on neurodegenerative diseases: Insights from a mendelian randomization study.}, journal = {Journal of cellular and molecular medicine}, volume = {28}, number = {20}, pages = {e70176}, pmid = {39470585}, issn = {1582-4934}, mesh = {Humans ; *Mendelian Randomization Analysis ; *Neurodegenerative Diseases/genetics/blood ; *Genome-Wide Association Study ; *Cytokines/blood/genetics ; Genetic Predisposition to Disease ; Polymorphism, Single Nucleotide ; Alzheimer Disease/genetics/blood ; Amyotrophic Lateral Sclerosis/genetics/blood ; Inflammation/genetics/blood ; Multiple Sclerosis/genetics/blood ; Parkinson Disease/genetics/blood ; }, abstract = {Neuroinflammation is increasingly recognized as a pivotal factor in the development and progression of neurodegenerative disorders. While correlations between inflammatory cytokines and these diseases are documented, the definitive causal dynamics remain to be elucidated. We explored the causal association between 91 circulating inflammatory cytokines and Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS) and Parkinson's disease (PD) through Mendelian randomization analysis. Leveraging genetic variants from the most comprehensive genome-wide association studies (GWAS) available for these cytokines, AD, ALS, MS and PD, we sought to uncover the causality. Our study validated a causal influence of genetically determined cytokine levels on the susceptibility to AD, with notable cytokines including C-X-C motif chemokine 1 (OR = 0.9993, p = 0.0424), Interleukin-18 (OR = 0.9994, p = 0.0186), Leukaemia inhibitory factor receptor (OR = 0.9993, p = 0.0122) and Monocyte chemoattractant protein-1 (OR = 0.9992, p = 0.0026) in risk attenuation. Additionally, a positive causal relationship was identified between two cytokines-C-C motif chemokine 19 (OR = 1.0005, p = 0.0478) and Fms-related tyrosine kinase 3 ligand (OR = 1.0005, p = 0.0210)-and AD incidence. Conversely, transforming growth factor-alpha (OR = 0.8630, p = 0.0298), CD40L receptor (OR = 0.7737, p = 1.1265E-09) and Interleukin-12 subunit beta (OR = 0.8987, p = 0.0333) showed inverse associations with ALS, MS and PD, respectively. The consistency observed in various MR analyses, alongside sensitivity analysis, underscored the absence of horizontal pleiotropy, thus supporting our causal findings. This study reveals, for the first time, a genetically anchored causal nexus between levels of circulating inflammatory cytokines and the risk of neurodegenerative diseases.}, } @article {pmid39470153, year = {2024}, author = {Xu, R}, title = {Overview of nomenclature and diagnosis of amyotrophic lateral sclerosis.}, journal = {Annals of medicine}, volume = {56}, number = {1}, pages = {2422572}, pmid = {39470153}, issn = {1365-2060}, mesh = {*Amyotrophic Lateral Sclerosis/diagnosis/classification/physiopathology ; Humans ; *Terminology as Topic ; Electromyography/methods ; Motor Neurons/pathology ; }, abstract = {The nomenclature of amyotrophic lateral sclerosis (ALS) currently is blurred, indistinct and no accurate and haven't been properly updated since the first description, which is far from being suitable for the current implementation of clinical practise and scientific research of ALS, and urgently need an solution. Furthermore, the current diagnostic criteria need also further been improved, because the current clinical diagnosis of ALS majorly depends on the clinical manifestations yet. Up to now, no any objective clinical auxiliary examination can be helpful to diagnose ALS besides the electromyogram identifying the lower motor neuron damage, which isn't conducive to early diagnosis and prolongs the time of ALS confirmed diagnosis. In this mini review, we discussed the current doubt about the nomenclature and diagnostic criteria of ALS, and prospected in order to further improve and normalize the nomenclature and diagnosis of ALS.}, } @article {pmid39468607, year = {2024}, author = {Liu, C and Wu, Y and Wang, F and Sun, S and Wei, J and Tao, L}, title = {Cost-utility analysis for sublingual versus intravenous edaravone in the treatment of amyotrophic lateral sclerosis.}, journal = {Orphanet journal of rare diseases}, volume = {19}, number = {1}, pages = {400}, pmid = {39468607}, issn = {1750-1172}, mesh = {*Edaravone/therapeutic use/economics/administration & dosage ; Humans ; *Amyotrophic Lateral Sclerosis/drug therapy/economics ; *Cost-Benefit Analysis ; Administration, Sublingual ; Antipyrine/analogs & derivatives/therapeutic use/economics/administration & dosage ; Free Radical Scavengers/therapeutic use/economics/administration & dosage ; Administration, Intravenous ; Male ; }, abstract = {BACKGROUND: Edaravone has been widely used in amyotrophic lateral sclerosis (ALS) treatment, and a sublingual (SL) tablet has been developed to offer a more convenient alternative for injection. We present a cost-utility analysis to comprehensively evaluate the costs and health outcomes of oral and intravenous edaravone for the treatment of ALS in Chinese medical context.

METHODS: Cost-utility analysis of SL tablets of edaravone versus intravenous edaravone at home was performed by constructing a 20-year Markov model of ALS stage 1-4 and death. The data were extracted from the literature with model assumptions. Typical sensitivity analysis and scenario analysis for administering SL tablets at home versus intravenous tablets at the hospital were performed.

RESULTS: In the base case analysis, with SL tablets and intravenous injections both at home, the model estimated an additional cost of ¥12,670.04 and an additional 0.034 QALYs over 20 years (life time) of modeling analysis, and the ICER was ¥372,648.24 per QALY. However, in the scenario of intravenous administration at the hospital, SL tablet was demonstrated dominance to intravenous injection.

CONCLUSIONS: Using 3 times the GDP per capita of China in 2023 as the threshold, the SL tablet edaravone was not cost-effective in the context of home treatment for both formulationst, but was dominance to intravenous injection in hospital treatment. The results highlighted the importance of treatment context for health economic analysis.}, } @article {pmid39467933, year = {2025}, author = {Kang, M and Kim, BJ and Nguyen, B and Park, JS}, title = {Computed tomography-based radiological gynecomastia in SBMA as an independent differential diagnostic biomarker: a retrospective study.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {46}, number = {2}, pages = {783-789}, doi = {10.1007/s10072-024-07820-1}, pmid = {39467933}, issn = {1590-3478}, mesh = {Humans ; *Gynecomastia/diagnostic imaging/etiology ; Retrospective Studies ; Middle Aged ; Male ; Diagnosis, Differential ; *Tomography, X-Ray Computed/methods ; Aged ; Adult ; *Amyotrophic Lateral Sclerosis/diagnostic imaging/complications ; *Bulbo-Spinal Atrophy, X-Linked/diagnostic imaging/complications ; }, abstract = {BACKGROUND: Spinal bulbar muscular atrophy (SBMA) and amyotrophic lateral sclerosis (ALS) are motor neuron disorders that demonstrate overlapping clinical features, especially in the early stage. Therefore, the aim of this study was to investigate the utility of chest tomography (CT) imaging in distinguishing between SBMA and ALS.

METHODS: This was a retrospective study reviewing CT images from patients with SBMA and sporadic ALS and those in the control group. The CT images were assessed to measure the diameter and morphology of glandular tissue associated with gynecomastia. We compared CT-measured gynecomastia between the SBMA, ALS, and control groups. Additionally, correlation analyses were performed between the quantitative measurements of gynecomastia obtained from CT scans and various clinical/laboratory parameter in the SBMA group.

RESULTS: 15 chest CT images were collected from SBMA, 41 from ALS, and 29 from control group. No statistical differences were observed in BMI, functional scales, or age at the time of CT scans between the SBMA and ALS groups. Despite similar functional scales and age in both groups, the mean glandular tissue diameter of breast tissue observed in chest CT imaging differed significantly between SBMA, ALS, and controls: 32.22 ± 12.57 mm, 15.91 ± 4.81 mm, and 15.76 ± 7.26 mm, respectively. This disparity allowed for the differentiation of SBMA from ALS and controls with statistical significance. Clinical gynecomastia was 80%, while radiological gynecomastia was 93.3% in SBMA. A significantly higher prevalence of diffuse glandular morphology pattern in SBMA (50%) was observed, contrasting with the predominance of nodular morphology in ALS and controls (9.1% and 20%). Correlative analysis between glandular tissue diameter and other clinical/laboratory parameters within the SBMA group showed no specific finding.

CONCLUSION: CT-based radiological gynecomastia effectively differentiated SBMA from ALS. These findings support the usefulness of radiological gynecomastia as a potential differential diagnostic marker for SBMA, especially in the early stages.}, } @article {pmid39466798, year = {2025}, author = {Correa, T and Owen, SR}, title = {Invited Commentary on: Santamaría-Gadea et al's "Non-Surgical Rhinoplasty After Rhinoplasty: A Systematic Review of the Technique, Results, and Complications".}, journal = {Facial plastic surgery & aesthetic medicine}, volume = {27}, number = {1}, pages = {75-76}, doi = {10.1089/fpsam.2024.0267}, pmid = {39466798}, issn = {2689-3622}, } @article {pmid39465944, year = {2024}, author = {Chen, C and Rafael, KA and Cho, G and Lim, Y}, title = {Split-Luciferase Reassembly Assay to Measure Endoplasmic Reticulum-Mitochondria Contacts in Live Cells.}, journal = {Journal of visualized experiments : JoVE}, volume = {}, number = {212}, pages = {}, pmid = {39465944}, issn = {1940-087X}, support = {R01 NS113516/NS/NINDS NIH HHS/United States ; }, mesh = {*Endoplasmic Reticulum/metabolism ; *Mitochondria/metabolism ; Humans ; Luciferases/metabolism/genetics ; Animals ; Mitochondria Associated Membranes ; }, abstract = {Endoplasmic reticulum (ER)-mitochondria contact sites play a critical role in cell health and homeostasis, such as the regulation of Ca[2+] and lipid homeostasis, mitochondrial dynamics, autophagosome and mitophagosome biogenesis, and apoptosis. Failure to maintain normal ER-mitochondrial coupling is implicated in many neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and hereditary spastic paraplegia. It is of considerable significance to explore how the dysregulation of ER-mitochondrial contacts could lead to cell death and whether repairing these contacts to the normal level could ameliorate neurodegenerative conditions. Thus, improved assays that measure the level of these contacts could help to illuminate the pathogenic mechanisms of these diseases. Ultimately, establishing simple and reliable assays will facilitate the development of new therapeutic strategies. Here we describe a split-luciferase assay to quantitatively measure the level of ER-mitochondria contacts in live cells. This assay can be used to study the pathophysiological role of these contacts as well as to identify their modulators in high-throughput screening.}, } @article {pmid39465642, year = {2024}, author = {Erdaş, ÇB and Sümer, E}, title = {CNN-Based Neurodegenerative Disease Classification Using QR-Represented Gait Data.}, journal = {Brain and behavior}, volume = {14}, number = {10}, pages = {e70100}, pmid = {39465642}, issn = {2162-3279}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/classification/diagnosis/physiopathology ; *Huntington Disease/diagnosis/physiopathology/classification ; *Parkinson Disease/classification/diagnosis/physiopathology ; *Neurodegenerative Diseases/classification/diagnosis/physiopathology ; Male ; Middle Aged ; Female ; Neural Networks, Computer ; Gait/physiology ; Aged ; Deep Learning ; Gait Analysis/methods ; Adult ; }, abstract = {PURPOSE: The primary aim of this study is to develop an effective and reliable diagnostic system for neurodegenerative diseases by utilizing gait data transformed into QR codes and classified using convolutional neural networks (CNNs). The objective of this method is to enhance the precision of diagnosing neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), and Huntington's disease (HD), through the introduction of a novel approach to analyze gait patterns.

METHODS: The research evaluates the CNN-based classification approach using QR-represented gait data to address the diagnostic challenges associated with neurodegenerative diseases. The gait data of subjects were converted into QR codes, which were then classified using a CNN deep learning model. The dataset includes recordings from patients with Parkinson's disease (n = 15), Huntington's disease (n = 20), and amyotrophic lateral sclerosis (n = 13), and from 16 healthy controls.

RESULTS: The accuracy rates obtained through 10-fold cross-validation were as follows: 94.86% for NDD versus control, 95.81% for PD versus control, 93.56% for HD versus control, 97.65% for ALS versus control, and 84.65% for PD versus HD versus ALS versus control. These results demonstrate the potential of the proposed system in distinguishing between different neurodegenerative diseases and control groups.

CONCLUSION: The results indicate that the designed system may serve as a complementary tool for the diagnosis of neurodegenerative diseases, particularly in individuals who already present with varying degrees of motor impairment. Further validation and research are needed to establish its wider applicability.}, } @article {pmid39464638, year = {2024}, author = {Altuwaijri, F and Alrabiah, A and Alqarni, A and Habash, AK and Alghofili, M and Alotaibi, O and Altuwaijri, M}, title = {Comparison Between the Advanced Cardiac Life Support and Adult Advanced Life Support Protocols: A Simulation-Based Pilot Study.}, journal = {Emergency medicine international}, volume = {2024}, number = {}, pages = {6696879}, pmid = {39464638}, issn = {2090-2840}, abstract = {Introduction: Cardiac arrest is a public health concern associated with unfavorable disease outcomes. Cardiopulmonary resuscitation (CPR) of optimal quality is widely acknowledged as an indispensable technique in restoring spontaneous circulation. In order to perform advanced cardiac life support (ACLS), chest compression must be paused twice: once to assess the rhythm and again to administer the shock. Australian advanced life support (ALS) recommends that the defibrillator needs to be precharged in order to administer the shock during a solitary interval in chest compressions. While performing chest compressions, precharging defibrillators can decrease hands-off time without posing a risk of injury. Aim: To compare chest compression fraction (CCF)-which is the cumulative time spent providing chest compressions divided by the total time taken for the entire resuscitation-by calculating the hands-off time duration in cardiac arrest between the Australian Resuscitation Council (ARC) and American Heart Association (AHA) protocols for CPR. Methods: A simulation-based pilot study was designed using a Laerdal Resusci Anne mannequin and a LIFEPACK 20 defibrillator. The study included six participants recruited from King Khalid University Hospital in Riyadh, Saudi Arabia, where three participants were certified ACLS providers and there were certified ALS providers. Participants were divided into two groups, ALS and ACLS, each following one protocol. For each scenario, a random job was assigned to each participant, regardless of their role as assistant, team leader, or performer of CPR. Each case's shockable and nonshockable rhythms were hidden from the team leader and the chest compressor. Ten trials of CPR were performed, each for four cycles with a total time of 8 min. The simulation was video recorded for hands-off time counting. Comparison between CCF (seconds) per cycle between the two protocols was performed using an independent sample t-test. A p value of 0.05 was used to measure statistical significance. Results: Comparing CCF in shockable rhythms between ARC and AHA protocols, it was observed that the CCF of ALS-ARC was significantly higher than ACLS-AHA in all cycles; the first cycle: t = 3.782, p=0.004; the second cycle: t = 3.380, p=0.007; the third cycle: t = 3.803, p=0.003; and the fourth cycle: t = 4.341, p=0.001. Conclusion: Precharging a defibrillator before a rhythm check during chest compression, in anticipation of a potentially shockable rhythm, reduces the time required for defibrillation and limits interruptions in chest compression during CPR. This practice effectively enhances the CCF. Enhancing the continuity of chest compressions can potentially improve survival rates in ARC.}, } @article {pmid39464461, year = {2024}, author = {Karunakaran, V and Dadgar, S and Paidi, SK and Mordi, AF and Lowe, WA and Mim, UM and Ivers, JD and Rodriguez Troncoso, JI and McPeake, JA and Fernandes, A and Tripathi, SD and Barman, I and Rajaram, N}, title = {Investigating In Vivo Tumor Biomolecular Changes Following Radiation Therapy Using Raman Spectroscopy.}, journal = {ACS omega}, volume = {9}, number = {42}, pages = {43025-43033}, pmid = {39464461}, issn = {2470-1343}, support = {P20 GM139768/GM/NIGMS NIH HHS/United States ; P41 EB015871/EB/NIBIB NIH HHS/United States ; R01 CA238025/CA/NCI NIH HHS/United States ; R15 CA238861/CA/NCI NIH HHS/United States ; }, abstract = {Treatment resistance is a major bottleneck in the success of cancer therapy. Early identification of the treatment response or lack thereof in patients can enable an earlier switch to alternative treatment strategies that can enhance response rates. Here, Raman spectroscopy was applied to monitor early tumor biomolecular changes in sensitive (UM-SCC-22B) and resistant (UM-SCC-47) head and neck tumor xenografts for the first time in in vivo murine tumor models in response to radiation therapy. We used a validated multivariate curve resolution-alternating least-squares (MCR-ALS) model to resolve complex multicomponent Raman spectra into individual pure spectra and their respective contributions. We observed a significant radiation-induced increase in the contributions of lipid-like species (p = 0.0291) in the radiation-sensitive UM-SCC-22B tumors at 48 h following radiation compared to the nonradiated baseline (prior to commencing treatment). We also observed an increase in the contribution of collagen-like species in the radiation-resistant UM-SCC-47 tumors at 24 h following radiation compared to the nonradiated baseline (p = 0.0125). In addition to the in vivo analysis, we performed ex vivo confocal Raman microscopic imaging of frozen sections derived from the same tumors. A comparison of all control and treated tumors revealed similar trends in the contributions of lipid-like and collagen-like species in both in vivo and ex vivo measurements; however, when evaluated as a function of time, longitudinal trends in the scores of collagen-like and lipid-like components were not consistent between the two data sets, likely due to sample numbers and differences in sampling depth at which information is obtained. Nevertheless, this study demonstrates the potential of fiber-based Raman spectroscopy for identifying early tumor microenvironmental changes in response to clinical doses of radiation therapy.}, } @article {pmid39464100, year = {2024}, author = {Du, M and Akerman, SC and Fare, CM and Ruan, L and Vidensky, S and Mamedova, L and Lee, J and Rothstein, JD}, title = {Divergent and Convergent TMEM106B Pathology in Murine Models of Neurodegeneration and Human Disease.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {39464100}, issn = {2692-8205}, support = {P50 AG005146/AG/NIA NIH HHS/United States ; R35 NS132179/NS/NINDS NIH HHS/United States ; }, abstract = {TMEM106B is a lysosomal/late endosome protein that is a potent genetic modifier of multiple neurodegenerative diseases as well as general aging. Recently, TMEM106B was shown to form insoluble aggregates in postmortem human brain tissue, drawing attention to TMEM106B pathology and the potential role of TMEM106B aggregation in disease. In the context of neurodegenerative diseases, TMEM106B has been studied in vivo using animal models of neurodegeneration, but these studies rely on overexpression or knockdown approaches. To date, endogenous TMEM106B pathology and its relationship to known canonical pathology in animal models has not been reported. Here, we analyze histological patterns of TMEM106B in murine models of C9ORF72-related amyotrophic lateral sclerosis and frontotemporal dementia (C9-ALS/FTD), SOD1-related ALS, and tauopathy and compare these to postmortem human tissue from patients with C9-ALS/FTD, Alzheimer's disease (AD), and AD with limbic-predominant age-related TDP-43 encephalopathy (AD/LATE). We show that there are significant differences between TMEM106B pathology in mouse models and human patient tissue. Importantly, we also identified convergent evidence from both murine models and human patients that links TMEM106B pathology to TDP-43 nuclear clearance specifically in C9-ALS. Similarly, we find a relationship at the cellular level between TMEM106B pathology and phosphorylated Tau burden in Alzheimer's disease. By characterizing endogenous TMEM106B pathology in both mice and human postmortem tissue, our work reveals considerations that must be taken into account when analyzing data from in vivo mouse studies and elucidates new insights supporting the involvement of TMEM106B in the pathogenesis and progression of multiple neurodegenerative diseases.}, } @article {pmid39463426, year = {2025}, author = {Yang, SF and Patel, PN}, title = {Invited Commentary on: Youssefi et al's 3D Smartphone Photography During Rhinoplasty Surgery.}, journal = {Facial plastic surgery & aesthetic medicine}, volume = {27}, number = {2}, pages = {199-200}, doi = {10.1089/fpsam.2024.0265}, pmid = {39463426}, issn = {2689-3622}, } @article {pmid39462586, year = {2024}, author = {Kurita, H and Hirasawa, N and Yabe, S and Okuda, A and Murakami, T and Ohuchi, K and Ogata, A and Yoshioka, H and Kakita, A and Hozumi, I and Inden, M}, title = {MicroRNA-5572 Is Associated with Endoplasmic Reticulum Stress Responses in Low Zinc Treated and SOD1 G85R-Transfected HEK293 Cells.}, journal = {Biological & pharmaceutical bulletin}, volume = {47}, number = {10}, pages = {1717-1725}, doi = {10.1248/bpb.b24-00418}, pmid = {39462586}, issn = {1347-5215}, mesh = {Humans ; *MicroRNAs/genetics/metabolism ; *Endoplasmic Reticulum Stress/drug effects/genetics ; *Superoxide Dismutase-1/genetics/metabolism ; *Zinc/metabolism ; *Amyotrophic Lateral Sclerosis/genetics/metabolism ; HEK293 Cells ; Transfection ; Tunicamycin/toxicity ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fetal neurodegenerative disease. The mechanism of sporadic ALS onset remains unclarified in detail. Disruption of zinc homeostasis could be related to sporadic ALS. Previously, we first reported miR-5572 as a microRNA (miRNA) among those identified in the spinal cords of patients with sporadic ALS. However, since its function in ALS remained unknown, this study further examined the role of miR-5572 in low-zinc status and ALS model cells which transfected with causative gene, Cu/Zn superoxide dismutase 1 (SOD1) G85R mutant vector. The miR-5572 level was increased by low-zinc condition accompanied by increase of endoplasmic reticulum (ER) stress. In addition, increase of miR-5572 enhanced the cellular toxicity induced by low-zinc treatment. The expression of miR-5572 was also increased, which was accompanied by an increase of ER stress markers associated with SOD1 aggregation formation. Cell death and ER stress makers levels induced by tunicamycin treatment were further increased in miR-5572 mimic-transfected cells. This study showed that miR-5572 exacerbated ER stress toxicity associated with low-zinc status and mutant SOD1 aggregates in ALS.}, } @article {pmid39462509, year = {2024}, author = {Dauer, LT and Mumma, MT and Lima, JC and Cohen, SS and Andresen, D and Bahadori, AA and Bellamy, M and Bierman, DA and Blattnig, S and French, B and Giunta, E and Held, K and Hertel, N and Keohane, L and Leggett, R and Lipworth, L and Miller, KB and Norman, RB and Samuels, C and Thomas, KS and Tolmachev, SY and Walsh, L and Boice, JD}, title = {A Million Person Study Innovation: Evaluating Cognitive Impairment and other Morbidity Outcomes from Chronic Radiation Exposure Through Linkages with the Centers for Medicaid and Medicare Services Assessment and Claims Data.}, journal = {Radiation research}, volume = {202}, number = {6}, pages = {847-861}, pmid = {39462509}, issn = {1938-5404}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; UE2 EH001315/EH/NCEH CDC HHS/United States ; 80NSSC17M0016/NASA/NASA/United States ; 80NSSC19M0161/NASA/NASA/United States ; DE-AU0000042//US Department of Energy/ ; DE-AU0000046//US Department of Energy/ ; 5NUE1EH001315//US Naval Sea Systems Command/ ; }, mesh = {Humans ; United States/epidemiology ; *Radiation Exposure/adverse effects ; Centers for Medicare and Medicaid Services, U.S. ; Male ; Medicare ; Female ; Cognition Disorders/epidemiology/etiology ; }, abstract = {The study of One Million U.S. Radiation Workers and Veterans, the Million Person Study (MPS), examines the health consequences, both cancer and non-cancer, of exposure to ionizing radiation received gradually over time. Recently the MPS has focused on mortality patterns from neurological and behavioral conditions, e.g., Parkinson's disease, Alzheimer's disease, dementia, and motor neuron disease such as amyotrophic lateral sclerosis. A fuller picture of radiation-related late effects comes from studying both mortality and the occurrence (incidence) of conditions not leading to death. Accordingly, the MPS is identifying neurocognitive diagnoses from fee-for-service insurance claims from the Centers for Medicare and Medicaid Services (CMS), among Medicare beneficiaries beginning in 1999 (the earliest date claims data are available). Linkages to date have identified ∼540,000 workers with available health information. Such linkages provide individual information on important co-factor and confounding variables such as smoking, alcohol consumption, blood pressure, obesity, diabetes and many other health and demographic characteristics. The total person-level set of time-dependent variables, outcomes, organ-specific dose measures, co-factors, and demographics will be massive and much too large to be evaluated with standard software. Thus, development of specialized open-source software designed for large datasets (Colossus) is nearly complete. The wealth of information available from CMS claims data, coupled with individual dose reconstructions, will thus greatly enhance the quality and precision of health evaluations for this new field of low-dose radiation and neurocognitive effects.}, } @article {pmid39461864, year = {2024}, author = {Imamura, K and Izumi, Y and Egawa, N and Ayaki, T and Nagai, M and Nishiyama, K and Watanabe, Y and Murakami, T and Hanajima, R and Kataoka, H and Kiriyama, T and Nanaura, H and Sugie, K and Hirayama, T and Kano, O and Nakamori, M and Maruyama, H and Haji, S and Fujita, K and Atsuta, N and Tatebe, H and Tokuda, T and Takahashi, N and Morinaga, A and Tabuchi, R and Oe, M and Kobayashi, M and Lobello, K and Morita, S and Sobue, G and Takahashi, R and Inoue, H}, title = {Protocol for a phase 2 study of bosutinib for amyotrophic lateral sclerosis using real-world data: induced pluripotent stem cell-based drug repurposing for amyotrophic lateral sclerosis medicine (iDReAM) study.}, journal = {BMJ open}, volume = {14}, number = {10}, pages = {e082142}, pmid = {39461864}, issn = {2044-6055}, mesh = {Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; *Amyotrophic Lateral Sclerosis/drug therapy ; *Aniline Compounds/therapeutic use ; Clinical Trials, Phase II as Topic ; *Drug Repositioning ; Induced Pluripotent Stem Cells ; Japan ; Multicenter Studies as Topic ; *Nitriles/therapeutic use ; Protein Kinase Inhibitors/therapeutic use ; *Quinolines/therapeutic use ; }, abstract = {INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a progressive, severe neurodegenerative disease caused by motor neuron death. Development of a medicine for ALS is urgently needed, and induced pluripotent cell-based drug repurposing identified a Src/c-Abl inhibitor, bosutinib, as a candidate for molecular targeted therapy of ALS. A phase 1 study confirmed the safety and tolerability of bosutinib in a 12-week treatment of ALS patients. The objectives of this study are to evaluate the efficacy and longer-term safety of bosutinib in ALS patients.

METHODS AND ANALYSIS: An open-label, multicentre phase 2 study was designed. The study consisted of a 12-week observation period, a 1-week transitional period, a 24-week study treatment period and a 4-week follow-up period. Following the transitional period, patients whose total Revised ALS Functional Rating Scale (ALSFRS-R) score declined by 1 to 4 points during the 12-week observation period were to receive bosutinib for 24 weeks. In this study, 25 ALS patients will be enrolled; patients will be randomly assigned to the following groups: 12 patients in the 200 mg quaque die (QD) group and 13 patients in the 300 mg QD group of bosutinib. The safety and exploratory efficacy of bosutinib in ALS patients for 24 weeks will be assessed. Efficacy using the ALSFRS-R score will be compared with the external published data from an edaravone study (MCI186-19) and registry data from a multicentre ALS cohort study, the Japanese Consortium for Amyotrophic Lateral Sclerosis Research.

ETHICS AND DISSEMINATION: This study was approved by the ethics committees of Kyoto University, Tokushima University, Kitasato University, Tottori University, Nara Medical University School of Medicine, Toho University and Hiroshima University. The findings will be disseminated in peer-reviewed journals and at scientific conferences.

TRIAL REGISTRATION NUMBER: jRCT2051220002; Pre-results, NCT04744532; Pre-results.}, } @article {pmid39461630, year = {2024}, author = {Kouhi, ZH and Seyedalipour, B and Hosseinkhani, S and Chaichi, MJ}, title = {Bisdemethoxycurcumin, a novel potent polyphenolic compound, effectively inhibits the formation of amyloid aggregates in ALS-associated hSOD1 mutant (L38R).}, journal = {International journal of biological macromolecules}, volume = {282}, number = {Pt 2}, pages = {136701}, doi = {10.1016/j.ijbiomac.2024.136701}, pmid = {39461630}, issn = {1879-0003}, mesh = {*Diarylheptanoids/chemistry/pharmacology ; Humans ; *Amyotrophic Lateral Sclerosis/genetics/drug therapy/metabolism ; *Protein Aggregates/drug effects ; *Amyloid/metabolism/chemistry ; *Superoxide Dismutase-1/genetics/metabolism/chemistry ; *Mutation ; *Molecular Dynamics Simulation ; *Molecular Docking Simulation ; Curcumin/pharmacology/analogs & derivatives/chemistry ; Polyphenols/pharmacology/chemistry ; Protein Aggregation, Pathological/genetics/drug therapy ; Hemolysis/drug effects ; Hydrophobic and Hydrophilic Interactions ; }, abstract = {Protein misfolding is a biological process that leads to protein aggregation. Anomalous misfolding and aggregation of human superoxide dismutase (hSOD1) into amyloid aggregates is a characteristic feature of amyotrophic lateral sclerosis (ALS), a neurodegenerative illness. Thus, focusing on the L38R mutant may be a wise decision to comprehend the SOD1 disease process in ALS. We suggest that Bisdemethoxycurcumin (BDMC) may be a strong anti-amyloidogenic polyphenol against L38R mutant aggregation. Protein stability, hydrophobicity, and flexibility were altered when BDMC was bound to the L38R mutant, as shown by molecular dynamic (MD) simulations and molecular docking. FTIR data shows α-Helix dominance in BDMC-containing samples, with reduced β-sheet and disordered peaks, indicating the decrease of aggregate species. ThT aggregation kinetics curves show BDMC reduces L38R mutant aggregation dose-dependently, with higher BDMC concentrations yielding greater reductions. TEM images showed various quantities of amorphous aggregates, but notably, 60 μM BDMC markedly reduced aggregate density, underscoring BDMC's inhibitory effect. Hemolysis tests revealed aggregate species in BDMC-treated samples were less toxic than in L38R mutant samples alone at the same concentrations and exposure times. Overall, BDMC has substantial potential to develop highly effective inhibitors that mitigate the risk of fatal ALS.}, } @article {pmid39461320, year = {2024}, author = {Didcote, L and Vitoratou, S and Al-Chalabi, A and Goldstein, LH}, title = {The reliability and validity of in-person and remote behavioural screening tools for people with amyotrophic lateral sclerosis.}, journal = {Journal of the neurological sciences}, volume = {466}, number = {}, pages = {123282}, doi = {10.1016/j.jns.2024.123282}, pmid = {39461320}, issn = {1878-5883}, support = {GOLDSTEIN/OCT17/892-792/MNDA_/Motor Neurone Disease Association/United Kingdom ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/psychology ; Male ; Female ; Middle Aged ; Reproducibility of Results ; Aged ; *Psychometrics/methods/standards ; Surveys and Questionnaires/standards ; Neuropsychological Tests/standards ; Adult ; }, abstract = {OBJECTIVE: This study aimed to assess the psychometric properties of and relationships between total scores on different screening tools assessing behavioural change for people with amyotrophic lateral sclerosis (ALS), and whether administering the screens as online questionnaires (rather than on paper, in-person) influences total scores.

METHODS: The behavioural component of the Edinburgh Cognitive and Behavioural ALS Screen (ECASb); the behavioural component of the ALS Cognitive Behavioural Screen (ALS-CBSb), the ALS-Frontotemporal Dementia Questionnaire (ALS-FTD-Q), the Beaumont Behavioural Inventory (BBI), and the Motor Neuron Disease Behavioural Instrument (MiND-B) were administered to 35 informants on paper. Online questionnaire versions of the behavioural screens were administered to 49 informants. Forward stepwise linear regressions were conducted to assess whether scores on behavioural screens were predicted by scores on the other behavioural screens and to assess whether total scores were predicted by the mode of administration (paper or online) of the screens.

RESULTS: Behavioural screening tools, except the ECASb, had good internal consistency but mixed item-total correlations. All regression models assessing whether behavioural screen scores predict other behavioural screen scores were significant. The BBI performed best and the ECASb performed worst in terms of their predictive relationships with other screening tools. The administration mode of the questionnaires did not significantly affect total scores.

CONCLUSIONS: The psychometric properties of the scales varied. The scales predicted each other's scores, supporting convergent validity. Online and paper versions performed similarly, and demographics did not predict scores.}, } @article {pmid39460670, year = {2025}, author = {Gondim, FAA and Fernandes, JMA}, title = {ALS due to c.1189 + 1G > T (splice donor) TBK1 mutation.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {26}, number = {1-2}, pages = {180}, doi = {10.1080/21678421.2024.2421754}, pmid = {39460670}, issn = {2167-9223}, } @article {pmid39459584, year = {2024}, author = {Silva, F and Silva, J and Salgueira, S and Mendes, A and Matos, E and Conde, B}, title = {Sleep Disturbances in Amyotrophic Lateral Sclerosis and Prognostic Impact-A Retrospective Study.}, journal = {Life (Basel, Switzerland)}, volume = {14}, number = {10}, pages = {}, pmid = {39459584}, issn = {2075-1729}, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease associated with sleep disturbance, namely insomnia and sleep-disordered breathing. This study aims to evaluate the overall sleep characteristics of ALS patients, their association with lung function tests, and possible predictive survival factors. We conducted a retrospective observation study among ALS patients monitored during a pulmonology consultation. Type one polysomnography (PSG) and lung function tests were performed once the patients presented with sleep-related symptoms, and the relationship between their parameters was assessed, as well as a survival analysis. We included 35 patients, with an overall diminished sleep efficiency, a partially conserved forced vital capacity (FVC), and low maximal inspiratory pressure (MIP). A positive correlation between FVC and REM sleep percentage was observed. A survival analysis showed that a normal rapid eye movement (REM) sleep percentage and respiratory disturbance index (RDI) ≥ 15/h were independent predictors of survival. We observed a trend for higher sleep quality in patients with conserved lung function. A better sleep quality was associated with a higher survival. Obstructive events (reduced or absence of airflow associated with continued or increased inspiratory effort) did not seem to impact survival.}, } @article {pmid39459534, year = {2024}, author = {Nakhal, MM and Yassin, LK and Alyaqoubi, R and Saeed, S and Alderei, A and Alhammadi, A and Alshehhi, M and Almehairbi, A and Al Houqani, S and BaniYas, S and Qanadilo, H and Ali, BR and Shehab, S and Statsenko, Y and Meribout, S and Sadek, B and Akour, A and Hamad, MIK}, title = {The Microbiota-Gut-Brain Axis and Neurological Disorders: A Comprehensive Review.}, journal = {Life (Basel, Switzerland)}, volume = {14}, number = {10}, pages = {}, pmid = {39459534}, issn = {2075-1729}, support = {12M159//UAEU/ ; G00004325//UAEU/ ; 12M142//UAEU/ ; }, abstract = {Microbes have inhabited the earth for hundreds of millions of years longer than humans. The microbiota-gut-brain axis (MGBA) represents a bidirectional communication pathway. These communications occur between the central nervous system (CNS), the enteric nervous system (ENS), and the emotional and cognitive centres of the brain. The field of research on the gut-brain axis has grown significantly during the past two decades. Signalling occurs between the gut microbiota and the brain through the neural, endocrine, immune, and humoral pathways. A substantial body of evidence indicates that the MGBA plays a pivotal role in various neurological diseases. These include Alzheimer's disease (AD), autism spectrum disorder (ASD), Rett syndrome, attention deficit hyperactivity disorder (ADHD), non-Alzheimer's neurodegeneration and dementias, fronto-temporal lobe dementia (FTLD), Wilson-Konovalov disease (WD), multisystem atrophy (MSA), Huntington's chorea (HC), Parkinson's disease (PD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), temporal lobe epilepsy (TLE), depression, and schizophrenia (SCZ). Furthermore, the bidirectional correlation between therapeutics and the gut-brain axis will be discussed. Conversely, the mood of delivery, exercise, psychotropic agents, stress, and neurologic drugs can influence the MGBA. By understanding the MGBA, it may be possible to facilitate research into microbial-based interventions and therapeutic strategies for neurological diseases.}, } @article {pmid39459490, year = {2024}, author = {Banciu, C and Chiriac, S and Pojoga, C and Marian, L and Fabian, A and Gogulescu, A and Simu, M and Parvanescu, R and Mioc, A and Racoviceanu, R and Munteanu, A}, title = {An Uncommon Overlap Syndrome Between Ankylosing Spondylitis and Amyotrophic Lateral Sclerosis-Case Report.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {60}, number = {10}, pages = {}, pmid = {39459490}, issn = {1648-9144}, support = {//"Victor Babes" University of Medicine and Pharmacy Timisoara/ ; }, mesh = {Humans ; *Spondylitis, Ankylosing/complications/drug therapy ; *Amyotrophic Lateral Sclerosis/complications/physiopathology ; Male ; Middle Aged ; Etanercept/therapeutic use ; Tumor Necrosis Factor-alpha/antagonists & inhibitors ; Syndrome ; }, abstract = {This case report describes an uncommon overlap syndrome between ankylosing spondylitis (AS) and amyotrophic lateral sclerosis (ALS). Initially, the patient was diagnosed with AS, for which he received various specific treatments, including TNF-α inhibitors. After five years of treatment with TNF-α inhibitor etanercept, the patient was referred for a full neurological assessment after he reported balance disturbances, postural instability, muscle weakness, and other neurological symptoms that indicated the presence of a neurological disorder. After a thorough investigation, the patient was diagnosed with ALS. This case report aims to contribute to the limited literature by providing a detailed case study regarding the crosstalk between AS and ALS while also exploring the potential underlying mechanisms and the possible link between TNF-α inhibitors therapy and ALS.}, } @article {pmid39459030, year = {2024}, author = {Al-Khayri, JM and Ravindran, M and Banadka, A and Vandana, CD and Priya, K and Nagella, P and Kukkemane, K}, title = {Amyotrophic Lateral Sclerosis: Insights and New Prospects in Disease Pathophysiology, Biomarkers and Therapies.}, journal = {Pharmaceuticals (Basel, Switzerland)}, volume = {17}, number = {10}, pages = {}, pmid = {39459030}, issn = {1424-8247}, support = {GRANT0000//Deanship of Scientific Research, King Faisal University/ ; }, abstract = {Amyotrophic Lateral Sclerosis (ALS) is a severe neurodegenerative disorder marked by the gradual loss of motor neurons, leading to significant disability and eventual death. Despite ongoing research, there are still limited treatment options, underscoring the need for a deeper understanding of the disease's complex mechanisms and the identification of new therapeutic targets. This review provides a thorough examination of ALS, covering its epidemiology, pathology, and clinical features. It investigates the key molecular mechanisms, such as protein aggregation, neuroinflammation, oxidative stress, and excitotoxicity that contribute to motor neuron degeneration. The role of biomarkers is highlighted for their importance in early diagnosis and disease monitoring. Additionally, the review explores emerging therapeutic approaches, including inhibitors of protein aggregation, neuroinflammation modulators, antioxidant therapies, gene therapy, and stem cell-based treatments. The advantages and challenges of these strategies are discussed, with an emphasis on the potential for precision medicine to tailor treatments to individual patient needs. Overall, this review aims to provide a comprehensive overview of the current state of ALS research and suggest future directions for developing effective therapies.}, } @article {pmid39458929, year = {2024}, author = {Giannakou, M and Akrani, I and Tsoka, A and Myrianthopoulos, V and Mikros, E and Vorgias, C and Hatzinikolaou, DG}, title = {Discovery of Novel Inhibitors against ALS-Related SOD1(A4V) Aggregation through the Screening of a Chemical Library Using Differential Scanning Fluorimetry (DSF).}, journal = {Pharmaceuticals (Basel, Switzerland)}, volume = {17}, number = {10}, pages = {}, pmid = {39458929}, issn = {1424-8247}, support = {MIS-5000432//state scholarship foundation (GR)/ ; }, abstract = {BACKGROUND: Cu/Zn Superoxide Dismutase 1 (SOD1) is a 32 kDa cytosolic dimeric metalloenzyme that neutralizes superoxide anions into oxygen and hydrogen peroxide. Mutations in SOD1 are associated with ALS, a disease causing motor neuron atrophy and subsequent mortality. These mutations exert their harmful effects through a gain of function mechanism, rather than a loss of function. Despite extensive research, the mechanism causing selective motor neuron death still remains unclear. A defining feature of ALS pathogenesis is protein misfolding and aggregation, evidenced by ubiquitinated protein inclusions containing SOD1 in affected motor neurons. This work aims to identify compounds countering SOD1(A4V) misfolding and aggregation, which could potentially aid in ALS treatment.

METHODS: The approach employed was in vitro screening of a library comprising 1280 pharmacologically active compounds (LOPAC[®]) in the context of drug repurposing. Using differential scanning fluorimetry (DSF), these compounds were tested for their impact on SOD1(A4V) thermal stability.

RESULTS AND CONCLUSIONS: Dimer stability was the parameter chosen as the criterion for screening, since the dissociation of the native SOD1 dimer is the step prior to its in vitro aggregation. The screening revealed one compound raising protein-ligand Tm by 6 °C, eleven inducing a higher second Tm, suggesting a stabilization effect, and fourteen reducing Tm from 10 up to 26 °C, suggesting possible interactions or non-specific binding.}, } @article {pmid39458862, year = {2024}, author = {Palacıoğlu, G}, title = {Chitosan, Methyl Jasmonate, and Silicon Induce Resistance to Angular Leaf Spot in Common Bean, Caused by Pseudocercospora griseola, with Expression of Defense-Related Genes and Enzyme Activities.}, journal = {Plants (Basel, Switzerland)}, volume = {13}, number = {20}, pages = {}, pmid = {39458862}, issn = {2223-7747}, abstract = {This study assessed the efficacy of chitosan, methyl jasmonate, and silicon in the reduction of disease severity and the induction of defense responses in common bean plants against angular leaf spot caused by Pseudocercospora griseola. The expression level of several pathogenesis-related (PR) proteins, PR1, PR2 (β-1,3-glucanase), and PR3 (chitinase), and defense-related enzymes, phenylalanine ammonia-lyase, peroxidase, and lipoxygenase, was analyzed at different time points in common bean plants after different treatments. Elicitor treatments significantly reduced disease severity 21 days after inoculation, with silicon at a 2 mM concentration proving most effective with 38.93% disease control, followed by 1 mM MeJA and 2% chitosan, respectively. Treatments with chitosan, methyl jasmonate, and silicon, regardless of pathogen infection, significantly elevated PR1, PR2, and PR3 gene expressions at 48 h after inoculation (hpi). PAL and POD activities were similarly increased following elicitor treatments and pathogen infection, especially at 48 hpi. Chemical elicitors applied post-inoculation induced PR proteins, PAL, and POD enzyme activities at 48 hpi, while LOX activity exhibited a variable fluctuation with treatments. These findings suggested that chemical elicitors, especially silicon, were effective in reducing ALS disease severity in common beans, with improved resistance associated with the expression of pathogen-responsive genes. This study is the first to analyze the expression profiles of defense-related genes in common beans treated with chemical elicitors prior to P. griseola infection.}, } @article {pmid39457680, year = {2024}, author = {McGrath, MS and Zhang, R and Bracci, PM and Azhir, A and Forrest, BD}, title = {Systemic Innate Immune System Restoration as a Therapeutic Approach for Neurodegenerative Disease: Effects of NP001 on Amyotrophic Lateral Sclerosis (ALS) Progression.}, journal = {Biomedicines}, volume = {12}, number = {10}, pages = {}, pmid = {39457680}, issn = {2227-9059}, support = {Neuvivo-NP001//Neuvivo, Inc./ ; }, abstract = {BACKGROUND/OBJECTIVE: Amyotrophic lateral sclerosis (ALS) is a diagnosis that incorporates a heterogeneous set of neurodegenerative processes into a single progressive and uniformly fatal disease making the development of a uniformly applicable therapeutic difficult. Recent multinational ALS natural history incidence studies have identified systemic chronic activation of the innate immune system as a major risk factor for developing ALS. Persistent immune activation in patients with ALS leads to loss of muscle and lowering of serum creatinine. The goal of the current study was to test whether the slowing of nerve and muscle destruction in NP001-treated ALS patients compared with controls in phase 2 studies would lead to extension of survival.

METHODS: Phase 2 clinical studies with NP001, an intravenously administered form of the innate immune system regulator NaClO2, are now reporting long-term survival benefits for drug recipients vs. placebo controls after only six months of intermittent treatment. As a prodrug, NP001 is converted by macrophages to taurine chloramine, a long-lived regulator of inflammation. We performed a pooled analysis of all patients who had completed the studies in two six-month NP001 phase 2 trials. Changes in respiratory vital capacity and the muscle mass product, creatinine, defined treated patients who, compared to placebo, had up to a year of extended survival.

CONCLUSIONS: The observed longer survival in ALS patients with the greatest inflammation-associated muscle loss provides further evidence that ALS is a disease of ongoing innate immune dysfunction and that NP001 is a disease-modifying drug with sustained clinical activity.}, } @article {pmid39457513, year = {2024}, author = {Montiel-Troya, M and Mohamed-Mohamed, H and Pardo-Moreno, T and González-Díaz, A and Ruger-Navarrete, A and de la Mata Fernández, M and Tovar-Gálvez, MI and Ramos-Rodríguez, JJ and García-Morales, V}, title = {Advancements in Pharmacological Interventions and Novel Therapeutic Approaches for Amyotrophic Lateral Sclerosis.}, journal = {Biomedicines}, volume = {12}, number = {10}, pages = {}, pmid = {39457513}, issn = {2227-9059}, support = {PID2019-110960GB-I00//Ministry of Science and Innovation, Spain./ ; }, abstract = {(1) Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease in which the patient suffers from an affection of both upper and lower motor neurons at the spinal and brainstem level, causing a progressive paralysis that leads to the patient's demise. Gender is also considered a predisposing risk factor for developing the disease. A brief review of the pathophysiological mechanisms of the disease is also described in this work. Despite the fact that a cure for ALS is currently unknown, there exists a variety of pharmacological and non-pharmacological therapies that can help reduce the progression of the disease over a certain period of time and alleviate symptoms. (2) We aim to analyze these pharmacological and non-pharmacological therapies through a systematic review. A comprehensive, multidisciplinary approach to treatment is necessary. (3) Drugs such as riluzole, edaravone, and sodium phenylbutyrate, among others, have been investigated. Additionally, it is important to stay updated on research on new drugs, such as masitinib, from which very good results have been obtained. (4) Therapies aimed at psychological support, speech and language, and physical therapy for the patient are also available, which increase the quality of life of the patients.}, } @article {pmid39457505, year = {2024}, author = {Seta, Y and Kimura, K and Masahiro, G and Tatsumori, K and Murakami, Y}, title = {SHED-CM: The Safety and Efficacy of Conditioned Media from Human Exfoliated Deciduous Teeth Stem Cells in Amyotrophic Lateral Sclerosis Treatment: A Retrospective Cohort Analysis.}, journal = {Biomedicines}, volume = {12}, number = {10}, pages = {}, pmid = {39457505}, issn = {2227-9059}, abstract = {BACKGROUND/OBJECTIVES: Amyotrophic lateral sclerosis (ALS) is a progressive and irreversible neurodegenerative disease with limited treatment options. Advances in regenerative medicine have opened up new treatment options. The primary and exploratory objectives of this retrospective cohort study were to evaluate the safety and efficacy of stem cells from human exfoliated deciduous teeth-conditioned media (SHED-CM).

METHODS: Safety assessments included adverse events, vital signs, and laboratory test changes before and after administration, and efficacy was measured using the ALS Functional Rating Scale-Revised (ALSFRS-R), grip strength, and forced vital capacity in 24 patients with ALS treated at a single facility between 1 January 2022, and 30 November 2023.

RESULTS: While ALSFRS-R scores typically decline over time, the progression rate in this cohort was slower, suggesting a potential delay in disease progression. Alternatively, improvements in muscle strength and mobility were observed in some patients. Although adverse events were reported in only 3% of cases (no serious allergic reactions), the treatment-induced changes in vital signs and laboratory results were not clinically significant.

CONCLUSIONS: The SHED-CM treatment is a safe and potentially effective therapeutic option for patients with ALS. Further research is needed to optimize the SHED-CM treatment; however, this study lays the groundwork for future exploration of regenerative therapies for ALS.}, } @article {pmid39457468, year = {2024}, author = {Boura, I and Giannopoulou, IA and Pavlaki, V and Xiromerisiou, G and Mitsias, P and Spanaki, C}, title = {FIG4-Related Parkinsonism and the Particularities of the I41T Mutation: A Review of the Literature.}, journal = {Genes}, volume = {15}, number = {10}, pages = {}, pmid = {39457468}, issn = {2073-4425}, mesh = {Humans ; *Parkinsonian Disorders/genetics/pathology/diagnostic imaging ; *Charcot-Marie-Tooth Disease/genetics/pathology ; *Flavoproteins/genetics ; Female ; Male ; Mutation, Missense ; Middle Aged ; Mutation ; Adult ; Phosphoric Monoester Hydrolases ; }, abstract = {Background/Objectives: The genetic underpinnings of Parkinson's disease (PD) and parkinsonism have drawn increasing attention in recent years. Mutations in the Factor-Induced Gene 4 (FIG4) have been implicated in various neurological disorders, including Charcot-Marie-Tooth disease type 4J (CMT4J), amyotrophic lateral sclerosis (ALS), and Yunis-Varón syndrome. This review aims to explore the association between FIG4 mutations and parkinsonism, with a specific focus on the rare missense mutation p.Ile41Thr (I41T). Methods: We identified 12 cases from 10 different families in which parkinsonism was reported in conjunction with CMT4J polyneuropathy. All cases involved the I41T mutation in a compound heterozygous state, combined with a FIG4 loss-of-function mutation. Data from clinical observations, neuroimaging studies, and genetic analyses were evaluated to understand the characteristics of parkinsonism in these patients. Results: In all 12 cases, parkinsonism developed either concurrently or following the onset of CMT4J neuropathy, but was never observed in isolation. Cases of both early- and late-onset parkinsonism were identified, reflecting similarities to genetic forms of parkinsonism with autosomal recessive inheritance. Imaging studies, including Dopamine transporter Single Photon Emission Computed Tomography (DaTscan) and brain magnetic resonance imaging (MRI), revealed abnormalities indicative of neurodegeneration, consistent with findings in other neurodegenerative disorders. Conclusions: The co-occurrence of parkinsonism with CMT4J in patients carrying the I41T mutation suggests an expanded spectrum of FIG4-related disorders, potentially implicating the same molecular mechanisms seen in other neurodegenerative disorders. Further research into FIG4-mediated pathways may offer valuable insights into potential therapeutic targets for disorders of both the central and peripheral nervous systems.}, } @article {pmid39457466, year = {2024}, author = {Moriyama, H and Yokota, T}, title = {Recent Progress of Antisense Oligonucleotide Therapy for Superoxide-Dismutase-1-Mutated Amyotrophic Lateral Sclerosis: Focus on Tofersen.}, journal = {Genes}, volume = {15}, number = {10}, pages = {}, pmid = {39457466}, issn = {2073-4425}, mesh = {*Amyotrophic Lateral Sclerosis/genetics/drug therapy/therapy ; Humans ; *Superoxide Dismutase-1/genetics ; *Oligonucleotides, Antisense/therapeutic use/genetics ; *Mutation ; Animals ; Oligonucleotides/therapeutic use/genetics ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a refractory neurodegenerative disease characterized by the degeneration and loss of motor neurons, typically resulting in death within five years of onset. There have been few effective treatments, making the development of robust therapies an urgent challenge. Genetic mutations have been identified as contributors to ALS, with mutations in superoxide dismutase 1 (SOD1), which neutralizes the harmful reactive oxygen species superoxide, accounting for approximately 2% of all ALS cases. To counteract the toxic gain of function caused by SOD1 mutations, therapeutic strategies aimed at suppressing SOD1 gene expression have shown promise. Antisense oligonucleotide (ASO) is an artificially synthesized, short, single-stranded DNA/RNA molecule that binds to target RNA to alter gene expression, representing a next-generation therapeutic approach. In 2023, tofersen became the first ASO drug approved by the FDA for ALS. Administered intrathecally, tofersen specifically binds to SOD1 mRNA, inhibiting the production of toxic SOD1 protein, thereby improving biomarkers of ALS. The long-term efficacy and safety of tofersen require further validation, and the development of more optimized treatment protocols is essential. A series of studies and therapeutic developments related to SOD1 mutations have advanced the understanding of ALS pathophysiology and significantly contributed to treatment strategies for central nervous system disorders. This review focuses on an overview of SOD1 mutations and the development process of tofersen, aiming to deepen the understanding of advancements in ALS research and discuss future challenges and directions for ASO therapy.}, } @article {pmid39456682, year = {2024}, author = {Alshehri, RS and Abuzinadah, AR and Alrawaili, MS and Alotaibi, MK and Alsufyani, HA and Alshanketi, RM and AlShareef, AA}, title = {A Review of Biomarkers of Amyotrophic Lateral Sclerosis: A Pathophysiologic Approach.}, journal = {International journal of molecular sciences}, volume = {25}, number = {20}, pages = {}, pmid = {39456682}, issn = {1422-0067}, mesh = {*Amyotrophic Lateral Sclerosis/metabolism/physiopathology/diagnosis ; Humans ; *Biomarkers/metabolism ; Motor Neurons/metabolism/pathology ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive degeneration of upper and lower motor neurons. The heterogeneous nature of ALS at the clinical, genetic, and pathological levels makes it challenging to develop diagnostic and prognostic tools that fit all disease phenotypes. Limitations associated with the functional scales and the qualitative nature of mainstay electrophysiological testing prompt the investigation of more objective quantitative assessment. Biofluid biomarkers have the potential to fill that gap by providing evidence of a disease process potentially early in the disease, its progression, and its response to therapy. In contrast to other neurodegenerative diseases, no biomarker has yet been validated in clinical use for ALS. Several fluid biomarkers have been investigated in clinical studies in ALS. Biofluid biomarkers reflect the different pathophysiological processes, from protein aggregation to muscle denervation. This review takes a pathophysiologic approach to summarizing the findings of clinical studies utilizing quantitative biofluid biomarkers in ALS, discusses the utility and shortcomings of each biomarker, and highlights the superiority of neurofilaments as biomarkers of neurodegeneration over other candidate biomarkers.}, } @article {pmid39456494, year = {2024}, author = {De Stefano, S and Tiberi, M and Salvatori, I and De Bardi, M and Gimenez, J and Pirshayan, M and Greco, V and Borsellino, G and Ferri, A and Valle, C and Mercuri, NB and Chiurchiù, V and Spalloni, A and Longone, P}, title = {Hydrogen Sulfide Modulates Astrocytic Toxicity in Mouse Spinal Cord Cultures: Implications for Amyotrophic Lateral Sclerosis.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {13}, number = {10}, pages = {}, pmid = {39456494}, issn = {2076-3921}, abstract = {Hydrogen sulfide (H2S), a known inhibitor of the electron transport chain, is endogenously produced in the periphery as well as in the central nervous system, where is mainly generated by glial cells. It affects, as a cellular signaling molecule, many different biochemical processes. In the central nervous system, depending on its concentration, it can be protective or damaging to neurons. In the study, we have demonstrated, in a primary mouse spinal cord cultures, that it is particularly harmful to motor neurons, is produced by glial cells, and is stimulated by inflammation. However, its role on glial cells, especially astrocytes, is still under-investigated. The present study was designed to evaluate the impact of H2S on astrocytes and their phenotypic heterogeneity, together with the functionality and homeostasis of mitochondria in primary spinal cord cultures. We found that H2S modulates astrocytes' morphological changes and their phenotypic transformation, exerts toxic properties by decreasing ATP production and the mitochondrial respiration rate, disturbs mitochondrial depolarization, and alters the energetic metabolism. These results further support the hypothesis that H2S is a toxic mediator, mainly released by astrocytes, possibly acting as an autocrine factor toward astrocytes, and probably involved in the non-cell autonomous mechanisms leading to motor neuron death.}, } @article {pmid39456257, year = {2024}, author = {Perni, M and Mannini, B}, title = {Targeting Protein Aggregation in ALS.}, journal = {Biomolecules}, volume = {14}, number = {10}, pages = {}, pmid = {39456257}, issn = {2218-273X}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism/genetics/drug therapy ; *Protein Aggregation, Pathological/metabolism ; Protein Aggregates ; Animals ; }, abstract = {Proteinopathies involve the abnormal accumulation of specific proteins. Maintaining the balance of the proteome is a finely regulated process managed by a complex network of cellular machinery responsible for protein synthesis, folding, and degradation. However, stress and ageing can disrupt this balance, leading to widespread protein aggregation. Currently, several therapies targeting protein aggregation are in clinical trials for ALS. These approaches mainly focus on two strategies: addressing proteins that are prone to aggregation due to mutations and targeting the cellular mechanisms that maintain protein homeostasis to prevent aggregation. This review will cover these emerging drugs. Advances in ALS research not only offer hope for better outcomes for ALS patients but also provide valuable insights and methodologies that can benefit the broader field of neurodegenerative disease drug discovery.}, } @article {pmid39456026, year = {2024}, author = {Albagli, EA and Calliari, A and Gendron, TF and Zhang, YJ}, title = {HDGFL2 cryptic protein: a portal to detection and diagnosis in neurodegenerative disease.}, journal = {Molecular neurodegeneration}, volume = {19}, number = {1}, pages = {79}, pmid = {39456026}, issn = {1750-1326}, support = {P01NS084974/NS/NINDS NIH HHS/United States ; U19AG063911/AG/NIA NIH HHS/United States ; R21NS127331/NS/NINDS NIH HHS/United States ; P01 AG019724/AG/NIA NIH HHS/United States ; R21 NS127331/NS/NINDS NIH HHS/United States ; R01NS121125/NS/NINDS NIH HHS/United States ; P01 NS084974/NS/NINDS NIH HHS/United States ; P30 AG062677/AG/NIA NIH HHS/United States ; R01NS117461/NS/NINDS NIH HHS/United States ; Target ALS//Target ALS/ ; R01 NS117461/NS/NINDS NIH HHS/United States ; U19 AG063911/AG/NIA NIH HHS/United States ; P30AG062677/AG/NIA NIH HHS/United States ; R01 AG085307/AG/NIA NIH HHS/United States ; R01AG085307/AG/NIA NIH HHS/United States ; }, } @article {pmid39455963, year = {2024}, author = {Alexander, E and Leong, KW}, title = {Discovery of nanobodies: a comprehensive review of their applications and potential over the past five years.}, journal = {Journal of nanobiotechnology}, volume = {22}, number = {1}, pages = {661}, pmid = {39455963}, issn = {1477-3155}, mesh = {*Single-Domain Antibodies/chemistry ; Humans ; Animals ; *SARS-CoV-2/immunology ; COVID-19/virology/immunology ; Neurodegenerative Diseases/drug therapy ; }, abstract = {Nanobodies (Nbs) are antibody fragments derived from heavy-chain-only IgG antibodies found in the Camelidae family as well as cartilaginous fish. Their unique structural and functional properties, such as their small size, the ability to be engineered for high antigen-binding affinity, stability under extreme conditions, and ease of production, have made them promising tools for diagnostics and therapeutics. This potential was realized in 2018 with the approval of caplacizumab, the world's first Nb-based drug. Currently, Nbs are being investigated in clinical trials for a broad range of treatments, including targeted therapies against PDL1 and Epidermal Growth Factor Receptor (EGFR), cardiovascular diseases, inflammatory conditions, and neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. They are also being studied for their potential for detecting and imaging autoimmune conditions and infectious diseases such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A variety of methods are now available to generate target-specific Nbs quickly and efficiently at low costs, increasing their accessibility. This article examines these diverse applications of Nbs and their promising roles. Only the most recent articles published in the last five years have been used to summarize the most advanced developments in the field.}, } @article {pmid39455931, year = {2024}, author = {Martínez, P and Silva, M and Abarzúa, S and Tevy, MF and Jaimovich, E and Constantine-Paton, M and Bustos, FJ and van Zundert, B}, title = {Skeletal myotubes expressing ALS mutant SOD1 induce pathogenic changes, impair mitochondrial axonal transport, and trigger motoneuron death.}, journal = {Molecular medicine (Cambridge, Mass.)}, volume = {30}, number = {1}, pages = {185}, pmid = {39455931}, issn = {1528-3658}, support = {1181645//Agencia Nacional de Investigación y Desarrollo/ ; DI-06-24/REG//UNAB/ ; 1221745//Agencia Nacional de Investigación y Desarrollo/ ; 21151265//Agencia Nacional de Investigación y Desarrollo/ ; R01-638 EY014420//National Institute of Mental Health and Neurosciences/ ; R01-EY014074//National Institute of Mental Health and Neurosciences/ ; R03 EY014420/EY/NEI NIH HHS/United States ; 1151293//Agencia Nacional de Investigación y Desarrollo/ ; 13220203 explorador//Agencia Nacional de Investigación y Desarrollo/ ; NCN2023_32//Agencia Nacional de Investigación y Desarrollo/ ; }, mesh = {Animals ; *Muscle Fibers, Skeletal/metabolism/pathology ; *Motor Neurons/metabolism/pathology ; *Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology ; *Mitochondria/metabolism ; *Superoxide Dismutase-1/genetics/metabolism ; Mice ; Humans ; *Mice, Transgenic ; *Axonal Transport ; Cell Death ; Disease Models, Animal ; Mutation ; Cells, Cultured ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the loss of motoneurons (MNs), and despite progress, there is no effective treatment. A large body of evidence shows that astrocytes expressing ALS-linked mutant proteins cause non-cell autonomous toxicity of MNs. Although MNs innervate muscle fibers and ALS is characterized by the early disruption of the neuromuscular junction (NMJ) and axon degeneration, there are controversies about whether muscle contributes to non-cell-autonomous toxicity to MNs. In this study, we generated primary skeletal myotubes from myoblasts derived from ALS mice expressing human mutant SOD1[G93A] (termed hereafter mutSOD1). Characterization revealed that mutSOD1 skeletal myotubes display intrinsic phenotypic and functional differences compared to control myotubes generated from non-transgenic (NTg) littermates. Next, we analyzed whether ALS myotubes exert non-cell-autonomous toxicity to MNs. We report that conditioned media from mutSOD1 myotubes (mutSOD1-MCM), but not from control myotubes (NTg-MCM), induced robust death of primary MNs in mixed spinal cord cultures and compartmentalized microfluidic chambers. Our study further revealed that applying mutSOD1-MCM to the MN axonal side in microfluidic devices rapidly reduces mitochondrial axonal transport while increasing Ca2 + transients and reactive oxygen species (i.e., H2O2). These results indicate that soluble factor(s) released by mutSOD1 myotubes cause MN axonopathy that leads to lethal pathogenic changes.}, } @article {pmid39454934, year = {2025}, author = {Takeda, T and Her, YR and Kim, JK and Jha, NN and Monani, UR}, title = {A variant of the Hspa8 synaptic chaperone modifies disease in a SOD1[G86R] mouse model of amyotrophic lateral sclerosis.}, journal = {Experimental neurology}, volume = {383}, number = {}, pages = {115024}, pmid = {39454934}, issn = {1090-2430}, support = {R01 NS104218/NS/NINDS NIH HHS/United States ; R01 NS123292/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; *Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology ; Mice ; *Disease Models, Animal ; *Mice, Transgenic ; *HSC70 Heat-Shock Proteins/metabolism/genetics ; *Superoxide Dismutase-1/genetics/metabolism ; Superoxide Dismutase/genetics/metabolism ; Motor Neurons/pathology/metabolism ; Humans ; Mutation ; Mice, Inbred C57BL ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a relatively common and invariably fatal, paralyzing motor neuron disease for which there are few treatment options. ALS is frequently associated with ubiquitin-positive motor neuronal aggregates, a pathology suggestive of perturbed proteostasis. Indeed, cellular chaperones, which are involved in protein trafficking and degradation often underlie familial ALS. Spinal muscular atrophy (SMA) is a second, common paralytic condition resulting from motor neuron loss and muscle atrophy. While SMA is now effectively treated, mechanisms underlying motor neuron degeneration in the disease remain far from clear. To address mechanistic questions about SMA, we recently identified a genetic modifier of the disease. The factor, a G470R variant in the constitutively expressed cellular chaperone, Hspa8, arrested motor neuron loss, prevented the abnormal accumulation of neurofilament aggregates at nerve terminals and suppressed disease. Hspa8 is best known for its role in autophagy. Amongst its many clients is the ALS-associated superoxide dismutase 1 (SOD1) protein. Given its suppression of the SMA phenotype, we tested potential disease-mitigating effects of Hspa8[G470R] in a mutant SOD1 mouse model of ALS. Unexpectedly, disease in mutant SOD1 mice expressing the G470R variant was aggravated. Motor performance of the mice deteriorated, muscle atrophy worsened, and lifespan shrunk even further. Paradoxically, SOD1 protein in spinal cord tissue of the mice was dramatically reduced. Our results suggest that Hspa8 modulates the ALS phenotype. However, rather than mitigating disease, the G470R variant exacerbates it.}, } @article {pmid39451992, year = {2024}, author = {Ozdinler, PH}, title = {Sleep Apnea and Amyotrophic Lateral Sclerosis: Cause, Correlation, Any Relation?.}, journal = {Brain sciences}, volume = {14}, number = {10}, pages = {}, pmid = {39451992}, issn = {2076-3425}, abstract = {Amyotrophic lateral sclerosis (ALS) is a motor neuron disease with progressive neurodegeneration, affecting both the cortical and the spinal component of the motor neuron circuitry in patients. The cellular and molecular basis of selective neuronal vulnerability is beginning to emerge. Yet, there are no effective cures for ALS, which affects more than 200,000 people worldwide each year. Recent studies highlight the importance of the glymphatic system and its proper function for the clearance of the cerebral spinal fluid, which is achieved mostly during the sleep period. Therefore, a potential link between problems with sleep and neurodegenerative diseases has been postulated. This paper discusses the present understanding of this potential correlation.}, } @article {pmid39451800, year = {2024}, author = {Drăgoi, MV and Nisipeanu, I and Frimu, A and Tălîngă, AM and Hadăr, A and Dobrescu, TG and Suciu, CP and Manea, AR}, title = {Real-Time Home Automation System Using BCI Technology.}, journal = {Biomimetics (Basel, Switzerland)}, volume = {9}, number = {10}, pages = {}, pmid = {39451800}, issn = {2313-7673}, abstract = {A Brain-Computer Interface (BCI) processes and converts brain signals to provide commands to output devices to carry out certain tasks. The main purpose of BCIs is to replace or restore the missing or damaged functions of disabled people, including in neuromuscular disorders like Amyotrophic Lateral Sclerosis (ALS), cerebral palsy, stroke, or spinal cord injury. Hence, a BCI does not use neuromuscular output pathways; it bypasses traditional neuromuscular pathways by directly interpreting brain signals to command devices. Scientists have used several techniques like electroencephalography (EEG) and intracortical and electrocorticographic (ECoG) techniques to collect brain signals that are used to control robotic arms, prosthetics, wheelchairs, and several other devices. A non-invasive method of EEG is used for collecting and monitoring the signals of the brain. Implementing EEG-based BCI technology in home automation systems may facilitate a wide range of tasks for people with disabilities. It is important to assist and empower individuals with paralysis to engage with existing home automation systems and gadgets in this particular situation. This paper proposes a home security system to control a door and a light using an EEG-based BCI. The system prototype consists of the EMOTIV Insight™ headset, Raspberry Pi 4, a servo motor to open/close the door, and an LED. The system can be very helpful for disabled people, including arm amputees who cannot close or open doors or use a remote control to turn on or turn off lights. The system includes an application made in Flutter to receive notifications on a smartphone related to the status of the door and the LEDs. The disabled person can control the door as well as the LED using his/her brain signals detected by the EMOTIV Insight™ headset.}, } @article {pmid39451396, year = {2024}, author = {Yang, CH and Huang, JL and Tsai, LK and Taniar, D and Pai, TW}, title = {An Effective DNA Methylation Biomarker Screening Mechanism for Amyotrophic Lateral Sclerosis (ALS) Based on Comorbidities and Gene Function Analysis.}, journal = {Bioengineering (Basel, Switzerland)}, volume = {11}, number = {10}, pages = {}, pmid = {39451396}, issn = {2306-5354}, support = {MOST 111-2221-E-027-113-414 MY2//National Science and Technology Council (Taiwan)/ ; NSTC113-2221-E-027-109//National Science and Technology Council (Taiwan)/ ; MOST104-2321-B-019-009//National Science and Technology Council (Taiwan)/ ; }, abstract = {This study used epigenomic methylation differential expression analysis to identify primary biomarkers in patients with amyotrophic lateral sclerosis (ALS). We combined electronic medical record datasets from MIMIC-IV (United States) and NHIRD (Taiwan) to explore ALS comorbidities in depth and discover any comorbidity-related biomarkers. We also applied word2vec to these two clinical diagnostic medical databases to measure similarities between ALS and other similar diseases and evaluated the statistical assessment of the odds ratio to discover significant comorbidities for ALS subjects. Important and representative DNA methylation biomarker candidates could be effectively selected by cross-comparing similar diseases to ALS, comorbidity-related genes, and differentially expressed methylation loci for ALS subjects. The screened epigenomic and comorbidity-related biomarkers were clustered based on their genetic functions. The candidate DNA methylation biomarkers associated with ALS were comprehensively discovered. Gene ontology annotations were then applied to analyze and cluster the candidate biomarkers into three different groups based on gene function annotations. The results showed that a potential testing kit for ALS detection can be composed of SOD3, CACNA1H, and ERBB4 for effective early screening of ALS using blood samples. By developing an effective DNA methylation biomarker screening mechanism, early detection and prophylactic treatment of high-risk ALS patients can be achieved.}, } @article {pmid39451238, year = {2024}, author = {Crescioli, C and Paronetto, MP}, title = {The Emerging Role of Phosphodiesterase 5 Inhibition in Neurological Disorders: The State of the Art.}, journal = {Cells}, volume = {13}, number = {20}, pages = {}, pmid = {39451238}, issn = {2073-4409}, mesh = {Humans ; *Phosphodiesterase 5 Inhibitors/therapeutic use/pharmacology ; *Nervous System Diseases/drug therapy ; Animals ; Cyclic Nucleotide Phosphodiesterases, Type 5/metabolism ; Neuroinflammatory Diseases/drug therapy/metabolism ; }, abstract = {Growing evidence suggests that neuroinflammation is not just a consequence of neurodegeneration in pathologies such as Alzheimer's disease, Parkinson's disease, Huntington's disease or Amyotrophic lateral sclerosis, but it is rather a determinant factor, which plays a pivotal role in the onset and progression of these disorders. Neuroinflammation can affect cells and processes in the central nervous system (CNS) as well as immune cells, and might precede protein aggregation, which is a hallmark of the neurodegenerative process. Standard treatment methods are far from being able to counteract inflammation and delay neurodegeneration. Remarkably, phosphodiesterase 5 inhibitors (PDE5is), which represent potent vasoactive drugs used as a first-line treatment for erectile dysfunction (ED), display important anti-inflammatory effects through cyclic guanosine monophosphate (cGMP) level stabilization. Since PDE5 hydrolyzes cGMP, several studies positioned PDE5 as a therapeutic target, and more specifically, PDE5is as potential alternative strategies for the treatment of a variety of neurological disorders. Indeed, PDE5is can limit neuroinflammation and enhance synaptic plasticity, with beneficial effects on cognitive function and memory. The aim of this review is to provide an overview of some of the main processes underlying neuroinflammation and neurodegeneration which may be potential targets for PDE5is, focusing on sildenafil, the most extensively studied. Current strategies using PDEis for the treatment of neurodegenerative diseases will be summarized.}, } @article {pmid39449756, year = {2024}, author = {Filipi, T and Tureckova, J and Vanatko, O and Chmelova, M and Kubiskova, M and Sirotova, N and Matejkova, S and Vargova, L and Anderova, M}, title = {ALS-like pathology diminishes swelling of spinal astrocytes in the SOD1 animal model.}, journal = {Frontiers in cellular neuroscience}, volume = {18}, number = {}, pages = {1472374}, pmid = {39449756}, issn = {1662-5102}, abstract = {Astrocytes are crucial for the functioning of the nervous system as they maintain the ion homeostasis via volume regulation. Pathological states, such as amyotrophic lateral sclerosis (ALS), affect astrocytes and might even cause a loss of such functions. In this study, we examined astrocytic swelling/volume recovery in both the brain and spinal cord of the SOD1 animal model to determine the level of their impairment caused by the ALS-like pathology. Astrocyte volume changes were measured in acute brain or spinal cord slices during and after exposure to hyperkalemia. We then compared the results with alterations of extracellular space (ECS) diffusion parameters, morphological changes, expression of the Kir4.1 channel and the potassium concentration measured in the cerebrospinal fluid, to further disclose the link between potassium and astrocytes in the ALS-like pathology. Morphological analysis revealed astrogliosis in both the motor cortex and the ventral horns of the SOD1 spinal cord. The activated morphology of SOD1 spinal astrocytes was associated with the results from volume measurements, which showed decreased swelling of these cells during hyperkalemia. Furthermore, we observed lower shrinkage of ECS in the SOD1 spinal ventral horns. Immunohistochemical analysis then confirmed decreased expression of the Kir4.1 channel in the SOD1 spinal cord, which corresponded with the diminished volume regulation. Despite astrogliosis, cortical astrocytes in SOD1 mice did not show alterations in swelling nor changes in Kir4.1 expression, and we did not identify significant changes in ECS parameters. Moreover, the potassium level in the cerebrospinal fluid did not deviate from the physiological concentration. The results we obtained thus suggest that ALS-like pathology causes impaired potassium uptake associated with Kir4.1 downregulation in the spinal astrocytes, but based on our data from the cortex, the functional impairment seems to be independent of the morphological state.}, } @article {pmid39449457, year = {2024}, author = {Rosa, D and Ingrande, L and Marcomini, I and Poliani, A and Villa, G and Sodano, M and Manara, DF}, title = {Perceived Pain in People Living with Amyotrophic Lateral Sclerosis-A Scoping Review.}, journal = {Nursing reports (Pavia, Italy)}, volume = {14}, number = {4}, pages = {3023-3039}, pmid = {39449457}, issn = {2039-4403}, abstract = {(1) Background: Pain is a common symptom in patients with Amyotrophic Lateral Sclerosis (ALS). There are no evidence-based pharmacological treatments for pain in ALS; recommendations are based on guidelines for chronic non-oncological pain and clinical experience. The aim is to map the literature on how people with ALS experience pain, and how this affects their daily activities and social relationships. (2) Methods: This scoping review included studies concerning patients with spinal/bulbar ALS aged ≥ 18 years who experience pain, focusing on perception, characteristics, treatment, and impact on quality of life. Temporal and linguistic criteria were applied when searching the MEDLINE, CINAHL, and SCOPUS databases. (3) Results: The management of pain in these patients is complex and involves the use of anti-inflammatory drugs, analgesics, and opioids. Pain is associated with other conditions such as depression and anxiety, which contribute to a deterioration in the quality of life. Moreover, pain may also negatively influence patient compliance with prescribed treatment regimens and the quality of care they perceive themselves to be receiving. (4) Conclusions: It is of the most importance to identify effective ways to assess and treat this issue, with health care professionals taking an active role in this process.}, } @article {pmid39449162, year = {2024}, author = {Zhu, Y and Zhang, Y and Li, M and Bai, J and Wang, H and Pang, X and Du, R and Wang, J and Huang, X}, title = {Prognostic Value of Systemic Inflammation, Nutritional Status and Sarcopenia in Patients With Amyotrophic Lateral Sclerosis.}, journal = {Journal of cachexia, sarcopenia and muscle}, volume = {15}, number = {6}, pages = {2743-2755}, pmid = {39449162}, issn = {2190-6009}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/complications/mortality/blood ; Female ; Male ; *Nutritional Status ; *Sarcopenia/etiology/blood ; Middle Aged ; Prognosis ; *Inflammation/blood ; Aged ; Biomarkers/blood ; Proportional Hazards Models ; ROC Curve ; Kaplan-Meier Estimate ; Adult ; }, abstract = {BACKGROUND: Nutritional status, systemic inflammatory responses and muscle mass are associated with the prognosis of patients with amyotrophic lateral sclerosis (ALS). However, the optimal biomarker for predicting prognosis remains unclear. This study aimed to identify the optimal indicators of survival among the nutrition-based, inflammation-based and muscle mass-related markers for ALS patients.

METHODS: We enrolled ALS patients from January 2014 to December 2019. Experienced neurologists followed up with the participants until January 2022. This study included a total of 17 nutritional, systemic inflammatory or muscle mass-related indicators. Maximally selected rank statistics determined the cut-off points for these indicators. Kaplan-Meier estimation was used to assess survival. Uni- and multivariate Cox proportional hazards models were used to determine the effects of indicators on survival. Finally, time-dependent receiver operating characteristic (time-ROC) curves and the C-index were calculated to evaluate the predictive efficacy of different indicators.

RESULTS: A total of 506 patients with ALS were enrolled in this study, including 288 males (56.9%) and 218 females (43.1%), with a mean age of 54.2 ± 10.5 years. Among these ALS patients, 334 cases (68.0%) either died or underwent tracheotomy. In univariate Cox proportional hazards regression, 11 indicators were significantly associated with ALS survival (p < 0.05). And systemic immune inflammation (SII), platelet-to-lymphocyte ratio (PLR), modified geriatric nutritional risk index (mGNRI), creatinine and sarcopenia index (SI, (creatinine/cystatin C) × 100) were determined as independent predictors (p < 0.05) in multivariate Cox proportional hazards regression. A higher SI predicted longer survival (hazard ratio, 0.59; 95% confidence interval [CI], 0.46-0.76; p < 0.001). The results of time-ROC and C-index analyses indicated that SI had the best predictive efficacy for ALS survival, with a C-index of 0.65 (95% CI, 0.54-0.75) for 1-year, 0.61 (95% CI, 0.57-0.65) for 3-year and 0.59 (95% CI, 0.55-0.62) for 5-year survival. Across different subgroups, SI had the highest C-index in men and women, limb onset and aged < 60 year ALS patients, compared with other indicators. However, cystatin C was the best indicator for predicting the survival of ALS patients with bulbar onset, whereas the prognostic nutritional index (PNI) was the best for those aged ≥60 years.

CONCLUSIONS: The serum SI demonstrates superior prognostic ability compared to other inflammation-based, nutrition-based and muscle mass-related indicators for patients with ALS. Given its simplicity and availability, it is well suited for clinical use in evaluating the prognosis of ALS patients.}, } @article {pmid39448670, year = {2024}, author = {Stankiewicz-Kosyl, M and Wińska-Krysiak, M and Wrochna, M and Haliniarz, M and Marcinkowska, K}, title = {Regional diversity of the ALS gene and hormesis due to tribenuron-methyl in Centaurea cyanus L.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {25197}, pmid = {39448670}, issn = {2045-2322}, support = {BIOSTRATEG 3/347445/1/NCBR/2017//The National Centre for Research and Development/ ; BIOSTRATEG 3/347445/1/NCBR/2017//The National Centre for Research and Development/ ; BIOSTRATEG 3/347445/1/NCBR/2017//The National Centre for Research and Development/ ; BIOSTRATEG 3/347445/1/NCBR/2017//The National Centre for Research and Development/ ; BIOSTRATEG 3/347445/1/NCBR/2017//The National Centre for Research and Development/ ; }, mesh = {*Acetolactate Synthase/genetics ; *Hormesis ; *Herbicides/pharmacology ; *Centaurea/genetics ; Arylsulfonates/pharmacology ; Herbicide Resistance/genetics ; Mutation ; Poland ; Plant Proteins/genetics ; Genetic Variation ; }, abstract = {Centaurea cyanus L. is a common field weed in Eastern Europe but only in Poland biotypes of this species with resistance to acetolactate synthase (ALS) inhibitors have been confirmed. This phenomenon is constantly developing and spreading to consecutive regions of Poland. This study aimed to assess the response of selected Polish C. cyanus populations to tribenuron-methyl and to analyse the genetic variability of the ALS gene of C. cyanus populations resistant to ALS inhibitors. Between 2017 and 2021, 13 seed samples were collected from eastern Poland and a dose-response study with tribenuron-methyl was performed. Eleven populations resistant to tribenuron-methyl were identified. All populations from this study as well as 6 additional resistant populations characterised in the previous dose-response studies were subjected to molecular analysis of the ALS gene. Target-site resistance due to mutations P197S, P197Q, P197T and P197A were identified in 8 populations from Warmia-Masuria and Podlaskie provinces. This is the first case of target-site resistance (TSR) in C. cyanus confirmed by sequencing of the ALS gene. Moreover in some resistant plants, ten changes in the amino acid ALS sequence were identified in comparison to those in the susceptible ones. In none of the populations were all mutations detected in the same individual. The highest frequency of mutations was detected in Warmia-Masuria province. Some C. cyanus populations resistant to ALS inhibitors showed hormesis effect concerning shoot fresh weight after tribenuron-methyl treatment. Stimulation due to half the recommended dose of tribenuron-methyl was the highest and the difference between untreated and treated plants was statistically significant in two populations from Warmia-Masuria and in one from Podlaskie province.}, } @article {pmid39447539, year = {2024}, author = {Zhu, H}, title = {Interference of nuclear speckles: A nexus of RNA foci, dipeptide repeats, and mis-splicing in C9ORF72 ALS/FTD.}, journal = {Neuron}, volume = {112}, number = {20}, pages = {3375-3377}, doi = {10.1016/j.neuron.2024.10.001}, pmid = {39447539}, issn = {1097-4199}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/metabolism ; *C9orf72 Protein/genetics ; *Frontotemporal Dementia/genetics/metabolism ; *RNA Splicing/genetics ; Dipeptides/metabolism ; DNA Repeat Expansion/genetics ; Proteins/genetics/metabolism ; RNA/genetics ; }, abstract = {In this issue of Neuron, Wu et al.[1] show that nuclear speckle proteins are sequestered by both nuclear RNA foci and cytoplasmic dipeptide repeat aggregates in C9ORF72-ALS/FTD. Consequently, dysregulation of splicing induces widespread splicing alterations and contributes to neurodegeneration.}, } @article {pmid39444183, year = {2025}, author = {Alici, H and Uversky, VN and Kang, DE and Woo, JA and Coskuner-Weber, O}, title = {Effects of the Amyotrophic Lateral Sclerosis-related Q108P Mutation on the Structural Ensemble Characteristics of CHCHD10.}, journal = {Current protein & peptide science}, volume = {26}, number = {3}, pages = {201-212}, pmid = {39444183}, issn = {1875-5550}, mesh = {*Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology ; Humans ; Molecular Dynamics Simulation ; *Mitochondrial Proteins/genetics/chemistry/metabolism ; *Mutation ; Principal Component Analysis ; Thermodynamics ; Protein Conformation ; }, abstract = {INTRODUCTION: The Q108P pathological variant of the mitochondrial Coiled-Coil-Helix-- Coiled-Coil-Helix Domain-Containing Protein 10 (CHCHD10) has been implicated in amyotrophic lateral sclerosis (ALS). Both the wild-type and CHCHD10[Q108P] proteins exhibit intrinsically disordered regions, posing challenges for structural studies with conventional experimental tools.

METHODS: This study presents the foundational characterization of the structural features of CHCHD10[Q108P] and compares them with those of the wild-type counterpart. We conducted multiple run molecular dynamics simulations and bioinformatics analyses.

RESULTS: Our findings reveal distinct differences in structural properties, free energy surfaces, and the outputs of principal component analysis between these two proteins. These results contribute significantly to the comprehension of CHCHD10 and its Q108P variant in terms of pathology, biochemistry, and structural biology.

CONCLUSION: The reported structural properties hold promise for informing the development of more effective treatments for ALS.}, } @article {pmid39444004, year = {2024}, author = {Hoshino, T and Mukai, A and Yamashita, H and Misawa, H and Urushitani, M and Tashiro, Y and Matsuzawa, SI and Takahashi, R}, title = {NDRG1 upregulation by ubiquitin proteasome system dysfunction aggravates neurodegeneration.}, journal = {Molecular brain}, volume = {17}, number = {1}, pages = {77}, pmid = {39444004}, issn = {1756-6606}, support = {16H01695//Japan Society for the Promotion of Science/ ; }, mesh = {Animals ; *Up-Regulation/genetics ; *Cell Cycle Proteins/metabolism/genetics ; *Proteasome Endopeptidase Complex/metabolism ; Mice ; *Ubiquitin/metabolism ; *Intracellular Signaling Peptides and Proteins/metabolism/genetics ; Cell Line, Tumor ; Motor Neurons/metabolism/pathology ; Nerve Degeneration/pathology ; Cell Death ; Humans ; }, abstract = {Protein turnover is crucial for cell survival, and the impairment of proteostasis leads to cell death. Aging is associated with a decline in proteostasis, as the progressive accumulation of damaged proteins is a hallmark of age-related disorders such as neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). We previously discovered that the declining function of the ubiquitin-proteasome system (UPS) in motor neurons contributes to sporadic ALS pathologies, such as progressive motor neuron loss, protein accumulation, and glial activation. However, the mechanisms of UPS dysfunction-induced cell damage, such as cell death and aggregation, are not fully understood. This study used transcriptome analysis of motor neurons with UPS dysfunction and found that the expression of N-myc downstream regulated 1 (NDRG1) gets upregulated by UPS dysfunction. Additionally, the upregulation of NDRG1 induces cell death in the Neuro2a mouse neuroblastoma cell line. These results suggest that NDRG1 is a potential marker for UPS dysfunction and may play a role in neurodegeneration, such as that seen in ALS.}, } @article {pmid39443862, year = {2024}, author = {Paulin, J and Lahti, M and Riihimäki, H and Hänninen, J and Vesanen, T and Koivisto, M and Peltonen, LM}, title = {The rate and predictors of violence against EMS personnel.}, journal = {BMC emergency medicine}, volume = {24}, number = {1}, pages = {200}, pmid = {39443862}, issn = {1471-227X}, mesh = {Humans ; Male ; Retrospective Studies ; Female ; Finland ; Adult ; Middle Aged ; *Emergency Medical Technicians/statistics & numerical data ; Emergency Medical Services/statistics & numerical data ; Workplace Violence/statistics & numerical data ; Violence/statistics & numerical data ; Logistic Models ; Electronic Health Records ; }, abstract = {BACKGROUND: Violence against Emergency Medical Services (EMS) personnel vary between studies. Current studies are mainly based on self-reporting, thus other designs are needed to provide more perspective. The purpose of this study was to explore the rate and predictors of violent behavior targeted at EMS personnel by exploring the Electronic patient care records (ePCR) documentation by EMS personnel.

METHODS: This was a retrospective cohort study of EMS patients in Finland. The data were collected from three regions between 1st June and 30th November 2018. Text mining and manual evaluation were used to identify and explore predictors of violence targeted at EMS personnel from the ePCR narratives. Multivariable logistic regressions were used to determine factors that were independently associated with violent behavior. The results are presented with odds ratios (ORs) with 95% confidence intervals (CIs).

RESULTS: The EMS personnel reported experiences of violence in a total of 297 identified missions (0.7%) of all EMS missions (n = 40,263). The violence was mostly verbal (62.3%) and the most common violence perpetrator was the patient (98.0%). The police were alarmed to many missions where violence was reported (40.7%). Sometimes violence occurred suddenly although the police were present. The multivariable logistic regression model indicates that violence occurred typically in urban areas (OR 1.699; 95% CI 1.283 to 2.248), at weekend nights (OR 1.357; 95% CI 1.043 to 1.765), by male (OR 1.501; 95% CI 1.160 to 1.942), and patients influenced by alcohol (OR 3.464; 95% CI 2.644 to 4.538). A NEWS2 score of 3 in any parameter (vs. score 0-4, OR 2.386; 95% CI: 1.788 to 3.185) and ALS unit type (vs. BLS, OR 1.373; 95% CI: 1.009 to 1.866) increased the likelihood as well.

CONCLUSIONS: The documentation in ePCRs show low rates of violence targeted at EMS personnel. However, violence is a multidimensional phenomenon connected to unfamiliar patients, rushed situations, and an uncontrolled environment. This means that the EMS personnels' safety cannot be ensured in all situations. Therefore, a balance between safety margins and treating patients needs to be considered.}, } @article {pmid39443410, year = {2024}, author = {Zhang, T and Rui, W and Sun, Y and Tian, Y and Li, Q and Zhang, Q and Zhao, Y and Liu, Z and Wang, T}, title = {Identification of nitric oxide-mediated necroptosis as the predominant death route in Parkinson's disease.}, journal = {Molecular biomedicine}, volume = {5}, number = {1}, pages = {44}, pmid = {39443410}, issn = {2662-8651}, mesh = {*Necroptosis ; *Parkinson Disease/pathology/metabolism/genetics ; *Nitric Oxide/metabolism ; Humans ; Animals ; Mice ; Neurons/metabolism/pathology ; Signal Transduction ; Male ; Brain/pathology/metabolism ; Alzheimer Disease/pathology/metabolism/genetics ; Amyotrophic Lateral Sclerosis/pathology/metabolism/genetics ; Membrane Potential, Mitochondrial ; }, abstract = {Parkinson's disease (PD) involves multiple forms of neuronal cell death, but the dominant pathway involved in disease progression remains unclear. This study employed RNA sequencing (RNA-seq) of brain tissue to explore gene expression patterns across different stages of PD. Using the Scaden deep learning algorithm, we predicted neurocyte subtypes and modelled dynamic interactions for five classic cell death pathways to identify the predominant routes of neuronal death during PD progression. Our cell type-specific analysis revealed an increasing shift towards necroptosis, which was strongly correlated with nitric oxide synthase (NOS) expression across most neuronal subtypes. In vitro experiments confirmed that nitric oxide (NO) is a key mediator of necroptosis, leading to nuclear shrinkage and decreased mitochondrial membrane potential via phosphorylation of the PIP1/PIP3/MLKL signalling cascade. Importantly, specific necroptosis inhibitors significantly mitigated neuronal damage in both in vitro and in vivo PD models. Further analysis revealed that NO-mediated necroptosis is prevalent in early-onset Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS) and across multiple brain regions but not in brain tumours. Our findings suggest that NO-mediated necroptosis is a critical pathway in PD and other neurodegenerative disorders, providing potential targets for therapeutic intervention.}, } @article {pmid39441150, year = {2024}, author = {Hamad, AA and Alkhawaldeh, IM and Abbas, A and Elaraby, A and Meshref, M}, title = {Incidence and risk factors of venous thromboembolism in patients with amyotrophic lateral sclerosis: a systematic review and meta-analysis.}, journal = {La Tunisie medicale}, volume = {102}, number = {10}, pages = {610-515}, pmid = {39441150}, issn = {2724-7031}, mesh = {*Amyotrophic Lateral Sclerosis/epidemiology/complications ; Humans ; *Venous Thromboembolism/epidemiology/etiology ; Incidence ; Risk Factors ; Male ; Female ; }, abstract = {AIMS: This systematic review and meta-analysis aimed to determine the annual incidence rate of venous thromboembolism (VTE) and identify risk factors of VTE in amyotrophic lateral sclerosis (ALS) patients.

METHODS: A comprehensive search of three databases was conducted up to April 8, 2024, to identify longitudinal studies reporting VTE incidence in ALS patients. The included studies were either prospective or retrospective, following up with ALS patients. Quality assessment was performed using the NIH tool for observational cohort studies. Meta-analysis was conducted using Open Meta Analyst, employing a random-effect model. Subgroup, Meta-regression, and sensitivity analyses were also carried out.

RESULTS: Our analysis included eight studies comprising a total of 26,758 ALS patients that met the inclusion criteria. The pooled annual incidence of VTE across all studies was found to be 22 cases per 1,000 person-year (95% CI = 18 to 27). Subgroup analysis revealed that the annual incidence of VTE in males was 19 cases per 1,000 person-year (95% CI = 15 to 22), while in females, it was 20 cases per 1,000 person-year (95% CI = 16 to 25). Leave-one-out analysis demonstrated that the incidence ranged from 21 to 28 cases per 1,000 person-year when excluding each study individually. Meta-regression analysis did not find a significant association between age and the risk of VTE (P = 0.079). Based on the included studies, risk factors of VTE in ALS patients included a history of VTE, non-invasive ventilation, immobility, and decreased functional status.

CONCLUSION: Patients with ALS face a higher risk of developing VTE compared to individuals of the same age. These findings underscore the importance of implementing preventive measures and closely monitoring VTE in ALS patients.}, } @article {pmid39441015, year = {2025}, author = {Liu, Y and Li, Y and Zhang, P}, title = {Stress granules and organelles: coordinating cellular responses in health and disease.}, journal = {Protein & cell}, volume = {16}, number = {6}, pages = {418-438}, pmid = {39441015}, issn = {1674-8018}, support = {2023YFC3505000//National Key Research and Development Project of China/ ; 7244365//Beijing Natural Science Foundation of China/ ; }, mesh = {Humans ; *Stress Granules/metabolism/pathology ; *Organelles/metabolism ; *Amyotrophic Lateral Sclerosis/metabolism/pathology ; Animals ; *Stress, Physiological ; *Cytoplasmic Granules/metabolism ; }, abstract = {Membrane-bound organelles and membraneless organelles (MLOs) coordinate various biological processes within eukaryotic cells. Among these, stress granules (SGs) are significant cytoplasmic MLOs that form in response to cellular stress, exhibiting liquid-like properties alongside stable substructures. SGs interact with diverse organelles, thereby influencing cellular pathways that are critical in both health and disease contexts. This review discusses the interplay between SGs and organelles and explores the methodologies employed to analyze interactions between SGs and other MLOs. Furthermore, it highlights the pivotal roles SGs play in regulating cellular responses and the pathogenesis of amyotrophic lateral sclerosis. Gaining insights into these interactions is essential for deciphering the mechanisms underlying both physiological processes and pathological conditions.}, } @article {pmid39440770, year = {2025}, author = {Allowitz, K and Taylor, J and Harames, K and Yoo, J and Baloch, O and Ramana, KV}, title = {Oxidative Stress-mediated Lipid Peroxidation-derived Lipid Aldehydes in the Pathophysiology of Neurodegenerative Diseases.}, journal = {Current neuropharmacology}, volume = {23}, number = {6}, pages = {671-685}, pmid = {39440770}, issn = {1875-6190}, mesh = {Humans ; *Oxidative Stress/physiology ; *Neurodegenerative Diseases/metabolism/physiopathology ; *Lipid Peroxidation/physiology ; *Aldehydes/metabolism ; Animals ; }, abstract = {Neurodegenerative diseases such as Alzheimer's, Parkinson's, and amyotrophic lateral sclerosis cause damage and gradual loss of neurons affecting the central nervous system. Neurodegenerative diseases are most commonly seen in the ageing process. Ageing causes increased reactive oxygen species and decreased mitochondrial ATP generation, resulting in redox imbalance and oxidative stress. Oxidative stress-generated free radicals cause damage to membrane lipids containing polyunsaturated fatty acids, leading to the formation of toxic lipid aldehyde products such as 4- hydroxynonenal and malondialdehyde. Several studies have shown that lipid peroxidation-derived aldehyde products form adducts with cellular proteins, altering their structure and function. Thus, these lipid aldehydes could act as secondary signaling intermediates, modifying important metabolic pathways, and contributing to the pathophysiology of several human diseases, including neurodegenerative disorders. Additionally, they could serve as biomarkers for disease progression. This narrative review article discusses the biological and clinical significance of oxidative stress-mediated lipid peroxidation-derived lipid aldehydes in the pathophysiology of various neurodegenerative diseases.}, } @article {pmid39440303, year = {2024}, author = {Dafinca, R and Tosat-Bitrian, C and Carroll, E and Vahsen, BF and Gilbert-Jaramillo, J and Scaber, J and Feneberg, E and Johnson, E and Talbot, K}, title = {Dynactin-1 mediates rescue of impaired axonal transport due to reduced mitochondrial bioenergetics in amyotrophic lateral sclerosis motor neurons.}, journal = {Brain communications}, volume = {6}, number = {5}, pages = {fcae350}, pmid = {39440303}, issn = {2632-1297}, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease of the motor system with complex determinants, including genetic and non-genetic factors. A key pathological signature of ALS is the cytoplasmic mislocalization and aggregation of TDP-43 in affected motor neurons, which is found in 97% of cases. Recent reports have shown that mitochondrial dysfunction plays a significant role in motor neuron degeneration in ALS, and TDP-43 modulates several mitochondrial transcripts. In this study, we used induced pluripotent stem cell-derived motor neurons from ALS patients with TDP-43 mutations and a transgenic TDP-43[M337V] mouse model to determine how TDP-43 mutations alter mitochondrial function and axonal transport. We detected significantly reduced mitochondrial respiration and ATP production in patient induced pluripotent stem cell-derived motor neurons, linked to an interaction between TDP-43[M337V] with ATPB and COX5A. A downstream reduction in speed of retrograde axonal transport in patient induced pluripotent stem cell-derived motor neurons was detected, which correlated with downregulation of the motor protein complex, DCTN1/dynein. Overexpression of DCTN1 in patient induced pluripotent stem cell-derived motor neurons significantly increased the percentage of retrograde travelling mitochondria and reduced the percentage of stationary mitochondria. This study shows that ALS induced pluripotent stem cell-derived motor neurons with mutations in TDP-43 have deficiencies in essential mitochondrial functions with downstream effects on retrograde axonal transport, which can be partially rescued by DCTN1 overexpression.}, } @article {pmid39439710, year = {2024}, author = {Kelser, BM and Teichner, EM and Subtirelu, RC and Hoss, KN}, title = {A review of proposed mechanisms for neurodegenerative disease.}, journal = {Frontiers in aging neuroscience}, volume = {16}, number = {}, pages = {1370580}, pmid = {39439710}, issn = {1663-4365}, abstract = {Neurodegenerative diseases, such as Alzheimer's, Parkinson's, and amyotrophic lateral sclerosis (ALS) affect millions and present significant challenges in healthcare and treatment costs. The debate in the field pivots around two hypotheses: synaptic spread and selective vulnerability. Pioneers like Virginia Lee and John Trojanowski have been instrumental in identifying key proteins (tau, alpha-synuclein, TDP-43) central to these diseases. The synaptic spread hypothesis suggests a cell-to-cell propagation of pathogenic proteins across neuronal synapses, influencing disease progression, with studies highlighting the role of proteins like alpha-synuclein and amyloid-beta in this process. In contrast, the selective vulnerability hypothesis proposes inherent susceptibility of certain neurons to degeneration due to factors like metabolic stress, leading to protein aggregation. Recent advancements in neuroimaging, especially PET/MRI hybrid imaging, offer new insights into these mechanisms. While both hypotheses offer substantial evidence, their relative contributions to neurodegenerative processes remain to be fully elucidated. This uncertainty underscores the necessity for continued research, with a focus on these hypotheses, to develop effective treatments for these devastating diseases.}, } @article {pmid39437787, year = {2024}, author = {Saez-Atienzar, S and Souza, CDS and Chia, R and Beal, SN and Lorenzini, I and Huang, R and Levy, J and Burciu, C and Ding, J and Gibbs, JR and Jones, A and Dewan, R and Pensato, V and Peverelli, S and Corrado, L and van Vugt, JJFA and van Rheenen, W and Tunca, C and Bayraktar, E and Xia, M and , and , and , and , and Iacoangeli, A and Shatunov, A and Tiloca, C and Ticozzi, N and Verde, F and Mazzini, L and Kenna, K and Al Khleifat, A and Opie-Martin, S and Raggi, F and Filosto, M and Piccinelli, SC and Padovani, A and Gagliardi, S and Inghilleri, M and Ferlini, A and Vasta, R and Calvo, A and Moglia, C and Canosa, A and Manera, U and Grassano, M and Mandrioli, J and Mora, G and Lunetta, C and Tanel, R and Trojsi, F and Cardinali, P and Gallone, S and Brunetti, M and Galimberti, D and Serpente, M and Fenoglio, C and Scarpini, E and Comi, GP and Corti, S and Del Bo, R and Ceroni, M and Pinter, GL and Taroni, F and Bella, ED and Bersano, E and Curtis, CJ and Lee, SH and Chung, R and Patel, H and Morrison, KE and Cooper-Knock, J and Shaw, PJ and Breen, G and Dobson, RJB and Dalgard, CL and , and Scholz, SW and Al-Chalabi, A and van den Berg, LH and McLaughlin, R and Hardiman, O and Cereda, C and Sorarù, G and D'Alfonso, S and Chandran, S and Pal, S and Ratti, A and Gellera, C and Johnson, K and Doucet-O'Hare, T and Pasternack, N and Wang, T and Nath, A and Siciliano, G and Silani, V and Başak, AN and Veldink, JH and Camu, W and Glass, JD and Landers, JE and Chiò, A and Sattler, R and Shaw, CE and Ferraiuolo, L and Fogh, I and Traynor, BJ}, title = {Mechanism-free repurposing of drugs for C9orf72-related ALS/FTD using large-scale genomic data.}, journal = {Cell genomics}, volume = {4}, number = {11}, pages = {100679}, pmid = {39437787}, issn = {2666-979X}, support = {R35 NS127253/NS/NINDS NIH HHS/United States ; }, mesh = {Humans ; *C9orf72 Protein/genetics ; *Amyotrophic Lateral Sclerosis/genetics/drug therapy ; *Drug Repositioning ; *Frontotemporal Dementia/genetics/drug therapy ; Genomics/methods ; Riluzole/therapeutic use ; Male ; Female ; Neuroprotective Agents/therapeutic use/pharmacology ; DNA Repeat Expansion/genetics ; }, abstract = {Repeat expansions in the C9orf72 gene are the most common genetic cause of (ALS) and frontotemporal dementia (FTD). Like other genetic forms of neurodegeneration, pinpointing the precise mechanism(s) by which this mutation leads to neuronal death remains elusive, and this lack of knowledge hampers the development of therapy for C9orf72-related disease. We used an agnostic approach based on genomic data (n = 41,273 ALS and healthy samples, and n = 1,516 C9orf72 carriers) to overcome these bottlenecks. Our drug-repurposing screen, based on gene- and expression-pattern matching and information about the genetic variants influencing onset age among C9orf72 carriers, identified acamprosate, a γ-aminobutyric acid analog, as a potentially repurposable treatment for patients carrying C9orf72 repeat expansions. We validated its neuroprotective effect in cell models and showed comparable efficacy to riluzole, the current standard of care. Our work highlights the potential value of genomics in repurposing drugs in situations where the underlying pathomechanisms are inherently complex. VIDEO ABSTRACT.}, } @article {pmid39436867, year = {2025}, author = {Firozjae, AA and Shiran, MR and Rashidi, M}, title = {The neuropharmacological and clinical effects of lutein: a systematic review.}, journal = {Hormone molecular biology and clinical investigation}, volume = {46}, number = {1}, pages = {27-38}, pmid = {39436867}, issn = {1868-1891}, mesh = {*Lutein/therapeutic use/pharmacology ; Humans ; *Neurodegenerative Diseases/drug therapy/metabolism ; Animals ; }, abstract = {OBJECTIVES: Neurodegenerative diseases are defined by specific protein accumulation and anatomic vulnerability leading to neuronal loss. Some studies have shown that lutein may have an effect on neurodegenerative diseases. As most of the neurodegenerative diseases don't have certain cure and therapies focus on symptom control, Lutein may be a complementary treatment. Due to controversies in studies investigating lutein effect on neurodegenerative diseases, we decided to perform a systematic review on these studies.

METHODS: A systematic search was carried out in the available databases. We used all MeSH terms and relevant keywords. Studies that reported relationship between lutein and any neurodegenerative disease were included.

RESULTS: We found 278 studies. After removing duplicates, screening by titles and abstracts and excluding irrelevant papers, 17 articles were included in this study. Fourteen studies investigated Alzheimer's disease, 2 studies Parkinson's disease and 1 study Amyotrophic lateral sclerosis. 1/17 study found that high serum levels of lutein at baseline were associated with a lower risk of AD mortality and lutein effect on lipid profile have been investigated in 2/17 studies. Also, 1/17 study has been shown that high intake of lutein may reduce the risk of ALS progression.

CONCLUSIONS: 4/17 studies confirm that lutein can improve cognitive function. 8/17 studies demonstrate a reduction in the progression of AD, and 2/17 studies indicate an improvement in lipid profiles. However, some studies did not find any significant associations. Additionally, there is a limited number of studies investigating the effects of lutein on other neurodegenerative diseases.}, } @article {pmid39436522, year = {2025}, author = {Ma, J and Wen, Q and Pang, X and Huang, S and Zhang, J and Wang, J and Chang, X and Guo, J and Zhang, W}, title = {Correction to: Fasciculation score: a sensitive biomarker in amyotrophic lateral sclerosis.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {46}, number = {1}, pages = {525-526}, doi = {10.1007/s10072-024-07807-y}, pmid = {39436522}, issn = {1590-3478}, } @article {pmid39435791, year = {2024}, author = {Brylev, LV and Bryukhov, VV and Druzhinina, ES and Kovalchuk, MO}, title = {[Lower motor neuron disease with MRI «snake eyes» pattern].}, journal = {Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova}, volume = {124}, number = {9}, pages = {141-144}, doi = {10.17116/jnevro2024124091141}, pmid = {39435791}, issn = {1997-7298}, mesh = {Humans ; *Magnetic Resonance Imaging ; *Motor Neuron Disease/diagnostic imaging/diagnosis ; Motor Neurons/pathology ; *Pyramidal Tracts/diagnostic imaging ; }, abstract = {Motor neuron disease with isolated or predominant lesion of the lower motor neuron at one level of the pyramidal tract is a rare diagnostic finding. In the article, we analyze the case of a patient with asymmetric lesion of the inferior motor neuron at the cervical level: clinical manifestations, results of additional studies and dynamic observation of the patient. Special attention is paid to the MRI picture of changes in the pyramidal tracts in the cervical region, which have been called the «snake eyes» in the literature, and the impact of this finding on the diagnosis and prognosis of the disease.}, } @article {pmid39435635, year = {2025}, author = {Yang, X and Gao, X and Jiang, X and Yue, K and Luo, P}, title = {Targeting capabilities of engineered extracellular vesicles for the treatment of neurological diseases.}, journal = {Neural regeneration research}, volume = {20}, number = {11}, pages = {3076-3094}, pmid = {39435635}, issn = {1673-5374}, abstract = {Recent advances in research on extracellular vesicles have significantly enhanced their potential as therapeutic agents for neurological diseases. Owing to their therapeutic properties and ability to cross the blood-brain barrier, extracellular vesicles are recognized as promising drug delivery vehicles for various neurological conditions, including ischemic stroke, traumatic brain injury, neurodegenerative diseases, glioma, and psychosis. However, the clinical application of natural extracellular vesicles is hindered by their limited targeting ability and short clearance from the body. To address these limitations, multiple engineering strategies have been developed to enhance the targeting capabilities of extracellular vesicles, thereby enabling the delivery of therapeutic contents to specific tissues or cells. Therefore, this review aims to highlight the latest advancements in natural and targeting-engineered extracellular vesicles, exploring their applications in treating traumatic brain injury, ischemic stroke, Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis, glioma, and psychosis. Additionally, we summarized recent clinical trials involving extracellular vesicles and discussed the challenges and future prospects of using targeting-engineered extracellular vesicles for drug delivery in treating neurological diseases. This review offers new insights for developing highly targeted therapies in this field.}, } @article {pmid39434139, year = {2024}, author = {Agah, E and Mojtabavi, H and Behkar, A and Heidari, A and Ajdari, A and Shaka, Z and Mousavi, SV and Firoozeh, N and Tafakhori, A and Rezaei, N}, title = {CSF and blood levels of Neurofilaments, T-Tau, P-Tau, and Abeta-42 in amyotrophic lateral sclerosis: a systematic review and meta-analysis.}, journal = {Journal of translational medicine}, volume = {22}, number = {1}, pages = {953}, pmid = {39434139}, issn = {1479-5876}, mesh = {Humans ; *Amyloid beta-Peptides/cerebrospinal fluid/blood ; *Amyotrophic Lateral Sclerosis/blood/cerebrospinal fluid/diagnosis ; Biomarkers/blood/cerebrospinal fluid ; Neurofilament Proteins/blood/cerebrospinal fluid ; Peptide Fragments/cerebrospinal fluid/blood ; Phosphorylation ; Publication Bias ; *tau Proteins/cerebrospinal fluid/blood ; }, abstract = {Recent literature suggests that markers of neuroaxonal damage, such as neurofilaments and tau protein, might serve as potential biomarkers for ALS. We conducted this systematic review and meta-analysis study to compare cerebrospinal fluid (CSF) and blood levels of total tau (t-tau), phosphorylated tau (p-tau), amyloid beta peptide 42 (Abeta-42), and neurofilaments in ALS patients and controls. A systematic search of Cochrane Library, PubMed, Embase, and ISI Web of Science was conducted on March 18, 2022, and updated on January 26, 2023. Observational studies that compared the concentrations of neurofilament light chain (NfL), neurofilament heavy chain (NFH), t-tau, p-tau, or Abeta-42 in CSF or peripheral blood of ALS patients and controls were included. Data from relevant studies were independently extracted and screened for quality using a standard tool, by at least two authors. Meta-analysis was conducted when a minimum of 3 studies reported the same biomarker within the same biofluid. A total of 100 studies were eligible for at least one meta-analysis. CSF and blood levels of NfL (standardized mean difference (SMD) [95% CI]; CSF: 1.46 [1.25-1.68]; blood: 1.35 [1.09-1.60]) and NFH (CSF: 1.32 [1.13-1.50], blood: 0.90 [0.58-1.22]) were significantly higher in ALS patients compared with controls. The pooled differences between ALS patients and controls were not significant for CSF t-tau, blood t-tau, and CSF Abeta-42, but CSF p-tau was lower in ALS patients (-0.27 [-0.47- -0.07]). Significantly decreased p-tau/t-tau ratios were found in ALS patients compared with controls (-0.84 [-1.16- -0.53]). Heterogeneity was considerable in most of our meta-analyses. CSF and blood neurofilament levels, as well as the CSF p-tau/t-tau ratio, might be potential candidates for improving ALS diagnosis. Further research is warranted to better understand the underlying mechanisms and the clinical implications of these biomarker alterations.}, } @article {pmid39434103, year = {2024}, author = {Sun, S and Chen, Y and Yun, Y and Zhao, B and Ren, Q and Sun, X and Meng, X and Yan, C and Lin, P and Liu, S}, title = {Elevated peripheral inflammation is associated with choroid plexus enlargement in independent sporadic amyotrophic lateral sclerosis cohorts.}, journal = {Fluids and barriers of the CNS}, volume = {21}, number = {1}, pages = {83}, pmid = {39434103}, issn = {2045-8118}, support = {qnts202306347//Taishan Young Scholar Program/ ; ZR2024MH178//Shandong Provincial Natural Science Foundation/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/blood/diagnostic imaging/pathology ; Male ; *Choroid Plexus/diagnostic imaging/pathology ; Female ; Middle Aged ; *Inflammation/blood/diagnostic imaging ; *Magnetic Resonance Imaging ; Cohort Studies ; Aged ; Adult ; }, abstract = {BACKGROUND: Using neuroimaging techniques, growing evidence has suggested that the choroid plexus (CP) volume is enlarged in multiple neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). Notably, the CP has been suggested to play an important role in inflammation-induced CNS damage under disease conditions. However, to our knowledge, no study has investigated the relationships between peripheral inflammation and CP volume in sporadic ALS patients. Thus, in this study, we aimed to verify CP enlargement and explore its association with peripheral inflammation in vivo in independent ALS cohorts.

METHODS: Based on structural MRI data, CP volume was measured using Gaussian mixture models and further manually corrected in two independent cohorts of sporadic ALS patients and healthy controls (HCs). Serum inflammatory protein levels were measured using a novel high-sensitivity Olink proximity extension assay (PEA) technique. Xtreme gradient boosting (XGBoost) was used to explore the contribution of peripheral inflammatory factors to CP enlargement. Then, partial correlation analyses were performed.

RESULTS: CP volumes were significantly higher in ALS patients than in HCs in the independent cohorts. Compared with HCs, serum levels of CRP, IL-6, CXCL10, and 35 other inflammatory factors were significantly increased in ALS patients. Using the XGBoost approach, we established a model-based importance of features, and the top three predictors of CP volume in ALS patients were CRP, IL-6, and CXCL10 (with gains of 0.24, 0.18, and 0.15, respectively). Correlation analyses revealed that CRP, IL-6, and CXCL10 were significantly associated with CP volume in ALS patients (r = 0.462 ∼ 0.636, p < 0.001).

CONCLUSION: Our study is the first to reveal a consistent and replicable contribution of peripheral inflammation to CP enlargement in vivo in sporadic ALS patients. Given that CP enlargement has been recently detected in other brain diseases, these findings should consider extending to other disease conditions with a peripheral inflammatory component.}, } @article {pmid39433597, year = {2024}, author = {Candrea, DN and Shah, S and Luo, S and Angrick, M and Rabbani, Q and Coogan, C and Milsap, GW and Nathan, KC and Wester, BA and Anderson, WS and Rosenblatt, KR and Uchil, A and Clawson, L and Maragakis, NJ and Vansteensel, MJ and Tenore, FV and Ramsey, NF and Fifer, MS and Crone, NE}, title = {A click-based electrocorticographic brain-computer interface enables long-term high-performance switch scan spelling.}, journal = {Communications medicine}, volume = {4}, number = {1}, pages = {207}, pmid = {39433597}, issn = {2730-664X}, support = {UH3 NS114439/NS/NINDS NIH HHS/United States ; }, abstract = {BACKGROUND: Brain-computer interfaces (BCIs) can restore communication for movement- and/or speech-impaired individuals by enabling neural control of computer typing applications. Single command click detectors provide a basic yet highly functional capability.

METHODS: We sought to test the performance and long-term stability of click decoding using a chronically implanted high density electrocorticographic (ECoG) BCI with coverage of the sensorimotor cortex in a human clinical trial participant (ClinicalTrials.gov, NCT03567213) with amyotrophic lateral sclerosis. We trained the participant's click detector using a small amount of training data (<44 min across 4 days) collected up to 21 days prior to BCI use, and then tested it over a period of 90 days without any retraining or updating.

RESULTS: Using a click detector to navigate a switch scanning speller interface, the study participant can maintain a median spelling rate of 10.2 characters per min. Though a transient reduction in signal power modulation can interrupt usage of a fixed model, a new click detector can achieve comparable performance despite being trained with even less data (<15 min, within 1 day).

CONCLUSIONS: These results demonstrate that a click detector can be trained with a small ECoG dataset while retaining robust performance for extended periods, providing functional text-based communication to BCI users.}, } @article {pmid39432543, year = {2024}, author = {Liu, X and Dong, L and Li, S and Li, Z and Wang, Y and Mao, Z and Deng, L}, title = {Improving AGB estimations by integrating tree height and crown radius from multisource remote sensing.}, journal = {PloS one}, volume = {19}, number = {10}, pages = {e0311642}, pmid = {39432543}, issn = {1932-6203}, mesh = {*Biomass ; *Trees/growth & development ; *Remote Sensing Technology/methods ; *Forests ; }, abstract = {Precise estimation of forest above ground biomass (AGB) is essential for assessing its ecological functions and determining forest carbon stocks. It is difficult to directly obtain diameter at breast height (DBH) based on remote sensing imagery. Therefore, it is crucial to accurately estimate the AGB with features extracted directly from RS. This paper demonstrates the feasibility of estimating AGB from crown radius (R) and tree height (H) features extracted from multi-source RS data. Accurate information on tree height (H), crown radius (R), and diameter at breast height (DBH) can be obtained through point clouds generated by airborne laser scanning (ALS) and terrestrial laser scanning (TLS), respectively. Nine allometric growth equations were used to fit coniferous forests (Larix principis-rupprechtii) and broadleaf forests (Fraxinus chinensis and Sophora japonica). The fitting performance of models constructed using only "H" or "R" was compared with that of models constructed using both combined. The results showed that the quadratic polynomial model constructed with "H+R" fitted the AGB estimation better in each vegetation type, especially in the scenario of mixed tall and short coniferous forests, in which the R2 and RMSE were 0.9282 and 25.30 kg (rRMSE 17.31%), respectively. Therefore, using high-resolution data to extract crown radius and tree height can achieve high-precision, global-scale estimation of forest above ground biomass.}, } @article {pmid39432435, year = {2025}, author = {Anjaneyulu, J and Godbole, A}, title = {Small organism models for mode of action research on anti-ageing and nootropic herbs, foods, and formulations.}, journal = {Nutritional neuroscience}, volume = {28}, number = {6}, pages = {744-762}, doi = {10.1080/1028415X.2024.2409128}, pmid = {39432435}, issn = {1476-8305}, mesh = {Animals ; *Aging/drug effects ; *Neurodegenerative Diseases/prevention & control/drug therapy ; Humans ; *Disease Models, Animal ; Zebrafish ; *Plant Extracts/pharmacology ; }, abstract = {With global increase in ageing population along with increasing age-related neurodegenerative diseases (NDs), development of sustainable, safe and effective solutions for promoting healthy ageing and preventing diseases has become a priority. Traditional healthcare systems/medicines prescribe several herbs, foods and formulations to promote healthy ageing and prevent and/or treat age-related diseases. However, the scientific data elucidating their mechanism of action is very limited and deeper research using different models is warranted for timely and wider use. The clinical studies and research with higher model organisms, although useful, have several practical, technical, and financial limitations. Conversely, small organism models like Yeast, Roundworm, Fruit fly, and Zebrafish, which have genetic similarities to humans, can replicate the disease features and provide behavioural, cellular and molecular insights. The common features of ageing and NDs, like amyloid protein aggregations, oxidative stress, energy dysregulation, inflammation and neurodegeneration can be mimicked in the small organism models for Alzheimer's, Parkinson's, Huntington's diseases, and Amyotrophic Lateral Sclerosis. This review focuses on small organism model- based research unveiling interesting modes of action and synergistic effects of herbal extracts, foods, and formulations, which are indicated especially for healthy ageing and management of NDs. This will provide leads for the quick and sustainable development of scientifically evaluated solutions for clinically relevant, age-related conditions.}, } @article {pmid39431591, year = {2025}, author = {Sheers, NL and Hannan, LM and Rautela, L and Graco, M and Jones, J and Retica, S and Saravanan, K and Burgess, N and McGaw, R and Donovan, A and Clohessy, T and Chao, C and Charles, C and Howard, ME and Berlowitz, DJ}, title = {NIV@Home: a pilot randomized controlled trial of in-home noninvasive ventilation initiation compared to a single-day admission model.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {26}, number = {3-4}, pages = {239-248}, doi = {10.1080/21678421.2024.2416668}, pmid = {39431591}, issn = {2167-9223}, mesh = {Humans ; *Noninvasive Ventilation/methods ; Male ; Pilot Projects ; Female ; Middle Aged ; Aged ; *Home Care Services ; Single-Blind Method ; *Respiratory Insufficiency/therapy/etiology ; *Neuromuscular Diseases/complications/therapy ; Quality of Life ; Adult ; Polysomnography ; }, abstract = {Objective: Noninvasive ventilation (NIV) is the primary treatment for respiratory insufficiency in neuromuscular disease. NIV implementation is usually conducted within hospitals; however, in-home implementation with intensive follow-up is an effective alternative. This pilot study aimed to assess model feasibility, acceptability, and NIV usage at 12-weeks after a single visit in-home implementation of NIV with remote monitoring follow-up (NIV@Home) compared to an in-hospital day admission NIV initiation plus planned polysomnography (Usual care). Methods: A single-blinded randomized controlled trial (www.anzctr.org.au ACTRN12620000682943) of adults with neuromuscular disease referred for NIV implementation. Participants were stratified by disease (MND or Other diagnoses) and bulbar symptoms before randomization to NIV@Home or Usual care, with follow-up at 12-weeks. The primary outcome was NIV usage. Secondary outcomes included feasibility, health-related quality of life, symptoms, carer burden, and NIV experience (semi-structured qualitative interviews). Results: Twenty-three participants (MND bulbar = 9, MND non-bulbar = 11, Other = 3) were randomized (NIV@Home = 9). No statistical differences were observed in the percentage of MND participants using NIV for >4 hours/day (NIV@Home = 33% vs. Usual care = 60%, p = 0.370), average use (NIV@Home = 2.4 [1.5-9.3] vs. 5.3 [1.8-7.0] hours/day, p = 0.568), or secondary outcomes. In-home NIV implementation was feasible and safe but took more therapist time (NIV@Home = 278 [270-305] vs. 172 [130-200] minutes, p < 0.001). Participants in the NIV@Home group reported substantial advantages to receiving care in home. Conclusion: In-home NIV implementation is feasible and acceptable to people with MND but requires more therapist time. Larger studies are required to determine whether there are clinically important differences between this model of NIV initiation and a traditional hospital-based model.}, } @article {pmid39431590, year = {2025}, author = {Correa-Arrieta, C and Castellar-Leones, S and Forero Diaz, JJ and Peña-Preciado, M and Ortiz-Corredor, F}, title = {Slowly progressing Amyotrophic lateral sclerosis associated with the F21L variant in the SOD1 gene: Demographic and clinical characteristics.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {26}, number = {3-4}, pages = {354-357}, doi = {10.1080/21678421.2024.2416669}, pmid = {39431590}, issn = {2167-9223}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/epidemiology/diagnosis ; Female ; Male ; Middle Aged ; Disease Progression ; *Superoxide Dismutase-1/genetics ; Adult ; Aged ; Colombia/epidemiology ; *Mutation/genetics ; Age of Onset ; }, abstract = {INTRODUCTION/OBJECTIVE: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease in which genetic variants can significantly influence clinical presentation and prognosis. This study aims to describe the demographic and clinical characteristics of ALS patients carrying the SOD1: c.63C > G (p.Phe21Leu) [NM_000454.4] variant, as treated at a national reference center in Colombia.

METHODS: A descriptive study was conducted on patients identified with the SOD1: c.63C > G (p.Phe21Leu) [NM_000454.4] variant, selected from the database of a neuromuscular disease center in Colombia. Demographic and clinical data were collected through medical records and patient interviews. Molecular analysis was performed using PCR and automated sequencing to confirm the presence of the variant.

RESULTS: Eleven patients with SOD1: c.63C > G (p.Phe21Leu) [NM_000454.4] variant were identified. The mean age at onset was 48.4 years, with a mean disease duration of 76.7 months. The majority (90.9%) exhibited a slowly progressive course, predominantly with spinal onset and no cognitive impairment. Bulbar symptoms developed in 72.2% of the patients, and 81.8% required noninvasive ventilation. A family history of ALS or other neurodegenerative disorders was present in 54.5% of the patients.

CONCLUSIONS: The SOD1: c.63C > G (p.Phe21Leu) [NM_000454.4] variant is associated with a slowly progressive ALS phenotype, characterized by predominant lower motor neuron involvement and delayed onset of bulbar and respiratory symptoms. This variant appears to be predominantly distributed in central Colombia. Early detection of this variant may enable timely interventions and personalized care plans. Further research is required to establish a definitive causal relationship between this variant and the observed clinical course.}, } @article {pmid39428513, year = {2024}, author = {Shibasaki, N and Konishi, K and Nishiyama, Y and Miyagawa, T and Numayama, T}, title = {[A case of amyotrophic lateral sclerosis managed by tracheostomy and invasive ventilation in which air leaks occurred at the cuff].}, journal = {Rinsho shinkeigaku = Clinical neurology}, volume = {64}, number = {11}, pages = {789-793}, doi = {10.5692/clinicalneurol.cn-001990}, pmid = {39428513}, issn = {1882-0654}, mesh = {Humans ; Female ; *Amyotrophic Lateral Sclerosis/therapy ; Middle Aged ; *Tracheostomy ; *Respiration, Artificial ; Tomography, X-Ray Computed ; Trachea/diagnostic imaging ; Air ; Pressure ; Treatment Outcome ; }, abstract = {The patient was a 64-year-old woman who had been diagnosed with amyotrophic lateral sclerosis 8 years ago, and had been under artificial ventilation with tracheotomy for 6 years. Computed tomography indicated a dilated tracheal diameter of 29.6 ‍mm at the cuff, and a high cuff pressure of 80 ‍cmH2O. An adjustable flange tracheostomy tube with an optional length setting was used to extend the effective length by 28 ‍mm. A previously evident air leak disappeared with the change in cuff level, and cuff pressure decreased to 25 ‍cmH2O. X-ray images indicated a reduction in the size of the previous cuff area. Tracheal dilatation due to improper management of cuff pressure is a contributing factor to air leakage at the cuff area, and using an adjustable flange tracheostomy tube in an effort to resolve such air leaks is a valid option.}, } @article {pmid39428436, year = {2024}, author = {Assialioui, A and Marco-Pascual, C and Torrente-Segarra, V and Domínguez, R and Santos, N and Peñafiel, J and Juanola, X and Povedano, M and Ferrer, I}, title = {Microvascular abnormalities in skin capillaries of individuals with amyotrophic lateral sclerosis.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {24648}, pmid = {39428436}, issn = {2045-2322}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/pathology/physiopathology ; Middle Aged ; Male ; *Capillaries/pathology ; Female ; *Skin/blood supply/pathology ; Aged ; Microscopic Angioscopy ; Case-Control Studies ; Adult ; }, abstract = {This is the first study aimed to detect morphological abnormalities in vivo in the skin capillaries of amyotrophic lateral sclerosis patients (ALS). Videocapillaroscopy assessed subungueal capillaries in 28 ALS patients (cases) and 35 controls (p = 0.42). The mean age was 61.46 and 61.23 years, respectively (p > 0.99). No statistically significant differences were observed between the groups regarding dominant hand, arterial hypertension, dyslipidemia, diabetes mellitus, active smoker, and former smoker variables. 78.57% of cases had spinal onset and 21.43% bulbar. The median disease duration (time between the onset of symptoms and the date of videocapillarscopy) was 29.71 months. Dilated capillaries were detected in 17.8% of cases and 11.43% of controls (p = 0.49). The median of capillary diameter in cases was 10.15 µm and 8.72 µm in controls (p = 0.011). 35.71% of cases and 2.86% of controls had severe capillary tortuosities (p < 0.001). Ramified capillaries were observed in 46.43% of cases and 11.43% of controls (p < 0.002). Micro-hemorrhages were only observed in 10.71% of cases. No significant correlations were observed between disease duration and dilated capillaries, tortuosity, ramified capillaries, and micro-hemorrhages. The present in vivo study shows abnormalities in the skin capillaries of ALS patients that do not depend on disease duration.}, } @article {pmid39428248, year = {2024}, author = {Luo, N and Wang, J and Zhang, ZY and Zhao, XY and Huang, RR and Wu, QY}, title = {[Research progress on Pb-induced neurotoxicity through glial cells].}, journal = {Zhonghua yu fang yi xue za zhi [Chinese journal of preventive medicine]}, volume = {58}, number = {10}, pages = {1610-1615}, doi = {10.3760/cma.j.cn112150-20240513-00382}, pmid = {39428248}, issn = {0253-9624}, support = {8217348282, 82173554, 82101593//National Natural Science Foundation of China/ ; }, mesh = {*Neuroglia/drug effects ; Humans ; *Lead/toxicity ; }, abstract = {Lead is one of the most important occupational hazards in China, and occupational exposure is the leading cause of lead poisoning. Lead can be absorbed by the body through air, food, drinking water and skin, and accumulate in multiple organs in the body, posing health risks to humans, especially to lead workers. Many previous studies have shown that lead can affect the function of glial cells such as microglia, astrocytes and oligodendrocytes, resulting in irreversible neurological damage. This article provides an overview of the neurotoxic mechanism induced by lead through glial cells, elucidates that lead can induce neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis, and reviews the relationship between lead and glial cells, in order to provide reference for further research on the neurotoxic mechanism of lead on glial cells.}, } @article {pmid39428001, year = {2025}, author = {Simoes, FA and Christoforidou, E and Cassel, R and Dupuis, L and Hafezparast, M}, title = {Severe dynein dysfunction in cholinergic neurons exacerbates ALS-like phenotypes in a new mouse model.}, journal = {Biochimica et biophysica acta. Molecular basis of disease}, volume = {1871}, number = {1}, pages = {167540}, doi = {10.1016/j.bbadis.2024.167540}, pmid = {39428001}, issn = {1879-260X}, mesh = {Animals ; *Disease Models, Animal ; Mice ; *Amyotrophic Lateral Sclerosis/metabolism/genetics/pathology ; *Phenotype ; *Cholinergic Neurons/metabolism/pathology ; Cytoplasmic Dyneins/metabolism/genetics ; Neuromuscular Junction/metabolism/pathology ; DNA-Binding Proteins/genetics/metabolism ; Mice, Knockout ; Male ; Dyneins/metabolism/genetics ; Point Mutation ; }, abstract = {Cytoplasmic dynein 1, a motor protein essential for retrograde axonal transport, is increasingly implicated in the pathogenesis of neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS). In this study, we developed a novel mouse model that combines the Legs at odd angles (Loa, F580Y) point mutation in the dynein heavy chain with a cholinergic neuron-specific knockout of the dynein heavy chain. This model, for the first time, allows us to investigate the impact of Loa allele exclusivity in these neurons into adulthood. Our findings reveal that this selective increase in dynein dysfunction exacerbated the phenotypes observed in heterozygous Loa mice including pre-wean survival, reduced body weight and grip strength. Additionally, it induced ALS-like pathology in neuromuscular junctions (NMJs) not seen in heterozygous Loa mice. Notably, we also found a previously unobserved significant increase in neurons displaying TDP-43 puncta in both Loa mutants, suggesting early TDP-43 mislocalisation - a hallmark of ALS. The novel model also exhibited a concurrent rise in p62 puncta that did not co-localise with TDP-43, indicating broader impairments in autophagic clearance mechanisms. Overall, this new model underscores the fact that dynein impairment alone can induce ALS-like pathology and provides a valuable platform to further explore the role of dynein in ALS.}, } @article {pmid39427550, year = {2024}, author = {Pan, Y and Sun, X and Tian, Y and Yu, M and Luo, Y and Sun, X}, title = {L-NRB alleviates amyotrophic lateral sclerosis by regulating P11-Htr4 signaling pathway.}, journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie}, volume = {180}, number = {}, pages = {117588}, doi = {10.1016/j.biopha.2024.117588}, pmid = {39427550}, issn = {1950-6007}, mesh = {*Amyotrophic Lateral Sclerosis/drug therapy/metabolism/pathology ; Animals ; *Signal Transduction/drug effects ; Mice ; *Neuroprotective Agents/pharmacology/therapeutic use ; Mice, Transgenic ; Male ; Benzofurans/pharmacology/therapeutic use ; Disease Models, Animal ; Motor Neurons/drug effects/pathology/metabolism ; Apoptosis/drug effects ; Mice, Inbred C57BL ; }, abstract = {INTRODUCTION: L-NRB is a compound formed as a ring cleavage product of butylphthalide and borneol in a molar ratio 1:2. This study aimed to explore the therapeutic effect of L-NRB on amyotrophic lateral sclerosis (ALS) and its possible mechanism.

METHODS: SOD1-G93A mice were used as an ALS model. Behavioral tests, histopathological staining, Nissl staining, immunohistochemistry, enzyme-linked immunosorbent assays, and Western blotting were used to analyze the therapeutic effect. The underlying mechanism of L-NRB in treating ALS was investigated using transcriptomic analyses.

RESULTS: It was found that L-NRB alleviated motor dysfunction, pathological changes in the gastrocnemius muscle, and motor neuron injuries. The results indicated that L-NRB had a neuroprotective function associated with the inhibition of neuroinflammation. The anti-apoptotic effect of L-NRB was found to be related to the regulation of the P11-Htr4 signaling pathway.

CONCLUSION: In summary, the results demonstrated the therapeutic effect of L-NRB on ALS and suggest a promising new therapeutic candidate for ALS.}, } @article {pmid39426615, year = {2024}, author = {Mackness, BC and Morgan, BR and Deveau, LM and Kathuria, SV and Zitzewitz, JA and Massi, F}, title = {A Hydrophobic Core Stabilizes the Residual Structure in the RRM2 Intermediate State of the ALS-linked Protein TDP-43.}, journal = {Journal of molecular biology}, volume = {436}, number = {22}, pages = {168823}, pmid = {39426615}, issn = {1089-8638}, support = {P41 GM103622/GM/NIGMS NIH HHS/United States ; R01 GM054836/GM/NIGMS NIH HHS/United States ; R01 GM137529/GM/NIGMS NIH HHS/United States ; }, mesh = {*Protein Folding ; *DNA-Binding Proteins/chemistry/metabolism/genetics ; Humans ; *Amyotrophic Lateral Sclerosis/genetics/metabolism ; *Hydrophobic and Hydrophilic Interactions ; *Molecular Dynamics Simulation ; Protein Structure, Secondary ; Protein Stability ; RNA Recognition Motif/genetics ; Protein Conformation ; Models, Molecular ; }, abstract = {Folding intermediates mediate both protein folding and the misfolding and aggregation observed in human diseases, including amyotrophic lateral sclerosis (ALS), and are prime targets for therapeutic interventions. In this study, we identified the core nucleus of structure for a folding intermediate in the second RNA recognition motif (RRM2) of the ALS-linked RNA-binding protein, TDP-43 (TAR DNA-binding protein-43), using a combination of experimental and computational approaches. Urea equilibrium unfolding studies revealed that the RRM2 intermediate state consists of collapsed residual secondary structure localized to the N-terminal half of RRM2, while the C-terminus is largely disordered. Steered molecular dynamics simulations and mutagenesis studies yielded key stabilizing hydrophobic contacts that, when mutated to alanine, severely disrupt the overall fold of RRM2. In combination, these findings suggest a role for this RRM intermediate in normal TDP-43 function as well as serving as a template for misfolding and aggregation through the low stability and non-native secondary structure.}, } @article {pmid39425598, year = {2024}, author = {Zhang, L and Zhou, X and Cha, S}, title = {Comprehensive Analysis of Sex Differences in Amyotrophic Lateral Sclerosis Prognosis and Disease Progression.}, journal = {Annals of neurology}, volume = {96}, number = {5}, pages = {1028}, doi = {10.1002/ana.27092}, pmid = {39425598}, issn = {1531-8249}, } @article {pmid39425590, year = {2025}, author = {Zhu, L and Li, Y and Yu, X and Chen, Y and Zhang, J and Pang, C and Xie, J and Gao, L and Du, L and Cao, W and Fan, D and Cui, C and Yu, H and Deng, B}, title = {Fighting Amyotrophic Lateral Sclerosis by Protecting the Liver? A Prospective Cohort Study.}, journal = {Annals of neurology}, volume = {97}, number = {2}, pages = {270-280}, doi = {10.1002/ana.27115}, pmid = {39425590}, issn = {1531-8249}, support = {12101460//National Natural Science Foundation of China/ ; 81901273//National Natural Science Foundation of China/ ; ZCLY24H0903//Natural Science Foundation of Zhejiang Province/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/epidemiology/diagnostic imaging/complications ; Male ; Female ; Middle Aged ; Prospective Studies ; Aged ; Magnetic Resonance Imaging ; Risk Factors ; *Liver Diseases/diagnostic imaging/epidemiology/complications ; Cohort Studies ; *Liver/diagnostic imaging ; Adult ; }, abstract = {BACKGROUND: Previous studies have observed liver abnormalities in amyotrophic lateral sclerosis (ALS) patients. This study aimed to investigate whether early signs of liver disease, measured by magnetic resonance imaging-derived iron-corrected T1-mapping (cT1), are risk factors for developing ALS.

METHODS: cT1 and proton density fat fraction were measured and automatically analyzed using LiverMultiScan® software. The Fibrosis-4 index was calculated using an established formula based on age and blood markers. Cox proportional hazard models were used to examine the relationship between liver disease, liver biomarkers, and incident ALS.

RESULTS: In a cohort of 533,707 individuals from UK Biobank, 24 ALS cases were identified among 28,328 participants with liver disease during the follow-up period. Among a total of 33,959 individuals with complete liver imaging data, 15 incident ALS cases were observed during a median follow-up period of 5.6 years. Individuals with liver disease had a higher risk of developing ALS, with an adjusted hazard ratio of 7.35 (95% CI 4.47-12.09; p < 0.001). An increase in cT1 was also associated with a higher risk of ALS. After adjusting for age, sex, Townsend deprivation index, smoking status, alcohol intake frequency, body mass index, proton density fat fraction, Fibrosis-4, and metabolic syndrome, an increase in cT1 remained significantly associated with a higher risk of ALS, with an adjusted hazard ratio of 3.15 (95% CI 1.79-5.55) per 1-SD increase. Sensitivity analyses confirmed these robust results.

INTERPRETATION: Liver disease activity, indicated by cT1, increases the risk of developing ALS, independent of metabolic syndrome, liver fat, or fibrosis. ANN NEUROL 2025;97:270-280.}, } @article {pmid39424779, year = {2024}, author = {Wu, H and Wang, LC and Sow, BM and Leow, D and Zhu, J and Gallo, KM and Wilsbach, K and Gupta, R and Ostrow, LW and Yeo, CJJ and Sobota, RM and Li, R}, title = {TDP43 aggregation at ER-exit sites impairs ER-to-Golgi transport.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {9026}, pmid = {39424779}, issn = {2041-1723}, support = {A-0007081-00-00//Ministry of Education - Singapore (MOE)/ ; NRF-MSG-2023-0001//National Research Foundation Singapore (National Research Foundation-Prime Minister's office, Republic of Singapore)/ ; NRF-SIS "SingMass"//A*STAR | Singapore Institute of Manufacturing Technology (Singapore Institute of Manufacturing Technology - A STAR)/ ; }, mesh = {Humans ; *Golgi Apparatus/metabolism ; *Endoplasmic Reticulum/metabolism ; *Amyotrophic Lateral Sclerosis/metabolism/genetics/pathology ; *DNA-Binding Proteins/metabolism/genetics ; Protein Transport ; Protein Aggregates ; Motor Neurons/metabolism ; HeLa Cells ; HEK293 Cells ; }, abstract = {Protein aggregation plays key roles in age-related degenerative diseases, but how different proteins coalesce to form inclusions that vary in composition, morphology, molecular dynamics and confer physiological consequences is poorly understood. Here we employ a general reporter based on mutant Hsp104 to identify proteins forming aggregates in human cells under common proteotoxic stress. We identify over 300 proteins that form different inclusions containing subsets of aggregating proteins. In particular, TDP43, implicated in Amyotrophic Lateral Sclerosis (ALS), partitions dynamically between two distinct types of aggregates: stress granule and a previously unknown non-dynamic (solid-like) inclusion at the ER exit sites (ERES). TDP43-ERES co-aggregation is induced by diverse proteotoxic stresses and observed in the motor neurons of ALS patients. Such aggregation causes retention of secretory cargos at ERES and therefore delays ER-to-Golgi transport, providing a link between TDP43 aggregation and compromised cellular function in ALS patients.}, } @article {pmid39424648, year = {2024}, author = {Chartier, C and Godard, J and Durand, S and Humeau-Heurtier, A and Menetrier, E and Allain, P and Besnard, J}, title = {Combinations of physical and cognitive training for subcortical neurodegenerative diseases with physical, cognitive and behavioral symptoms: a systematic review.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {45}, number = {12}, pages = {5571-5589}, pmid = {39424648}, issn = {1590-3478}, mesh = {Humans ; *Neurodegenerative Diseases/therapy ; Behavioral Symptoms/therapy/etiology ; Cognitive Behavioral Therapy/methods ; Exercise Therapy/methods ; Cognitive Dysfunction/therapy/rehabilitation/etiology ; Cognitive Training ; }, abstract = {BACKGROUND: The onset of the symptoms of subcortical NDs is due to a unique part of the brain which strengthens the idea of reciprocal influence of physical activity and cognitive training in improving clinical symptoms. Consequently, protocols combining the two stimulations are becoming increasingly popular in NDs. Our threefold aim was to (A) describe the different combinations of physical and cognitive training used to alleviate the motor and cognitive symptoms of patients with subcortical neurodegenerative disorders, (B) compare the effects of these different combinations (sequential, dual tasking, synergical) on symptoms, and (C) recommend approaches for further studies.

METHODS: We conducted literature searches of PubMed, BASE and ACM, to carry out a systematic review of randomized controlled trials and controlled trials of combined physical and cognitive training among patients with Huntington's disease, Parkinson's disease, amyotrophic lateral sclerosis, Lewy body dementia, spinocerebellar ataxia, Friedreich's ataxia, and progressive supranuclear palsy. Physical, neuropsychological, behavioral outcomes were considered. The Cochrane risk-of-bias tool was used to verify the critical appraisal.

RESULTS: Twenty-one studies focused on Parkinson's disease with 940 participants were included. Despites promising benefits on cognitive and physical function, our results revealed discrepant findings for research on combined training.

DISCUSSION: Inconsistencies were linked to the choice of tests, the functions that were targeted, disease progression, and trainings. There was a dearth of follow-up data.

CONCLUSIONS: Differences between combined training are unclear, particularly regarding the role of cognitive load. Future studies should focus on comparing the feasibility, tolerability, and effectiveness of different combinations of motor-cognitive training.}, } @article {pmid39424561, year = {2024}, author = {Crow, YJ}, title = {CNS disease associated with enhanced type I interferon signalling.}, journal = {The Lancet. Neurology}, volume = {23}, number = {11}, pages = {1158-1168}, pmid = {39424561}, issn = {1474-4465}, support = {786142/ERC_/European Research Council/International ; MC_UU_00035/11/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Humans ; *Interferon Type I/metabolism/immunology ; *Signal Transduction ; Animals ; Central Nervous System Diseases/immunology/metabolism ; }, abstract = {The ability to mount an interferon-mediated innate immune response is essential in protection against neurotropic viruses, but antiviral type I interferons also have neurotoxic potential. The production of type I interferons can be triggered by self-derived nucleic acids, and the brain can be susceptible to inappropriate upregulation of type I interferon signalling. Homoeostatic dysregulation of type I interferons has been implicated in rare inborn errors of immunity (referred to as type I interferonopathies) and more common neurodegenerative disorders (eg, Parkinson's disease, Alzheimer's disease, and amyotrophic lateral sclerosis). Recent developments include new insights into the pathogenesis of these disorders that involve dysregulated type I interferon signalling, as well as advances in their diagnosis and management. The role of type I interferons in brain cellular health suggests the future therapeutic potential of approaches that target these interferons and their signalling.}, } @article {pmid39424560, year = {2024}, author = {Koch, JC and Leha, A and Bidner, H and Cordts, I and Dorst, J and Günther, R and Zeller, D and Braun, N and Metelmann, M and Corcia, P and De La Cruz, E and Weydt, P and Meyer, T and Großkreutz, J and Soriani, MH and Attarian, S and Weishaupt, JH and Weyen, U and Kuttler, J and Zurek, G and Rogers, ML and Feneberg, E and Deschauer, M and Neuwirth, C and Wuu, J and Ludolph, AC and Schmidt, J and Remane, Y and Camu, W and Friede, T and Benatar, M and Weber, M and Lingor, P and , }, title = {Safety, tolerability, and efficacy of fasudil in amyotrophic lateral sclerosis (ROCK-ALS): a phase 2, randomised, double-blind, placebo-controlled trial.}, journal = {The Lancet. Neurology}, volume = {23}, number = {11}, pages = {1133-1146}, doi = {10.1016/S1474-4422(24)00373-9}, pmid = {39424560}, issn = {1474-4465}, mesh = {Humans ; *1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine/analogs & derivatives/therapeutic use/pharmacology/adverse effects ; Middle Aged ; Male ; Double-Blind Method ; Female ; *Amyotrophic Lateral Sclerosis/drug therapy ; Aged ; Adult ; *rho-Associated Kinases/antagonists & inhibitors ; *Protein Kinase Inhibitors/adverse effects/therapeutic use/administration & dosage ; Treatment Outcome ; Aged, 80 and over ; Young Adult ; Adolescent ; }, abstract = {BACKGROUND: Fasudil is a small molecule inhibitor of Rho-associated kinase (ROCK) and is approved for the treatment of subarachnoid haemorrhage. In preclinical studies, fasudil has been shown to attenuate neurodegeneration, modulate neuroinflammation, and foster axonal regeneration. We aimed to investigate the safety, tolerability, and efficacy of fasudil in patients with amyotrophic lateral sclerosis.

METHODS: ROCK-ALS was a phase 2, randomised, double-blind, placebo-controlled trial conducted at 19 amyotrophic lateral sclerosis centres in Germany, France, and Switzerland. Individuals (aged 18-80 years) with at least probable amyotrophic lateral sclerosis (as per the revised El Escorial criteria), a disease duration of 6-24 months, and a slow vital capacity greater than 65% of predicted normal were eligible for inclusion. Patients were randomly assigned (1:1:1) to receive 30 mg (15 mg twice daily) or 60 mg (30 mg twice daily) fasudil or matched placebo intravenously for 20 days over a 4-week period. Follow-up assessments were performed at 45, 90, and 180 days after treatment initiation. The co-primary endpoints were safety until day 180 (defined as the proportion without drug-related serious adverse events) and tolerability during the treatment period (defined as the proportion who did not discontinue treatment due to suspected drug-related adverse events). The primary analyses were carried out in the intention-to-treat population, which included all participants who entered the treatment phase. This trial is registered at ClinicalTrials.gov (NCT03792490) and Eudra-CT (2017-003676-31) and is now completed.

FINDINGS: Between Feb 20, 2019, and April 20, 2022, 120 participants were enrolled and randomised; two individuals assigned fasudil 30 mg withdrew consent before the baseline visit. Thus, the intention-to-treat population comprised 35 in the fasudil 30 mg group, 39 in the fasudil 60 mg group, and 44 in the placebo group. The estimated proportion without a drug-related serious adverse event was 1·00 (95% CI 0·91 to 1·00) with placebo, 1·00 (0·89 to 1·00) with fasudil 30 mg, and 1·00 (0·90 to 1·00) with fasudil 60 mg; the difference in proportions was 0·00 (95% CI -0·11 to 0·10; p>0·99) for fasudil 30 mg versus placebo and 0·00 (-0·10 to 0·10; p>0·99) for fasudil 60 mg versus placebo. Treatment tolerability (the estimated proportion who did not discontinue) was 0·93 (95% CI 0·81 to 0·99) with placebo, 1·00 (0·90 to 1·00) with fasudil 30 mg, and 0·90 (0·76 to 0·97) with fasudil 60 mg; the difference in proportions was 0·07 (95% CI -0·05 to 0·20; p=0·25) for fasudil 30 mg versus placebo, and -0·03 (-0·18 to 0·10; p=0·70) for fasudil 60 mg versus placebo. Eight deaths occurred: two in the placebo group, four in the fasudil 30 mg group, and two in the fasudil 60 mg group. The most common serious adverse events were respiratory failure (seven events), gastrostomy (five events), pneumonia (four events), and dysphagia (four events). No serious adverse events or deaths were attributed to study treatment. Adverse events, which were mainly related to disease progression, occurred in 139 participants in the placebo group, 108 in the fasudil 30 mg group, and 105 in the fasudil 60 mg group.

INTERPRETATION: Fasudil was well tolerated and safe in people with amyotrophic lateral sclerosis. The effect of fasudil on efficacy outcomes should be explored in larger clinical trials with a longer treatment duration, oral administration, and potentially higher dose of the trial drug.

FUNDING: Framework of the E-Rare Joint Transnational Call 2016 "Clinical research for new therapeutic uses of already existing molecules (repurposing) in rare diseases".}, } @article {pmid39424548, year = {2024}, author = {Andrews, JA}, title = {A new era of drug discovery for amyotrophic lateral sclerosis.}, journal = {The Lancet. Neurology}, volume = {23}, number = {11}, pages = {1070-1072}, doi = {10.1016/S1474-4422(24)00407-1}, pmid = {39424548}, issn = {1474-4465}, } @article {pmid39424348, year = {2025}, author = {Yoganathan, S and Kumar, M and Aaron, R and Rangan, SR and Umakant, BS and Thomas, M and Oommen, SP and Danda, S}, title = {Phenotype and Genotype of Children with ALS2 gene-Related Disorder.}, journal = {Neuropediatrics}, volume = {56}, number = {1}, pages = {20-28}, doi = {10.1055/s-0044-1791256}, pmid = {39424348}, issn = {1439-1899}, mesh = {Humans ; Male ; Female ; *Amyotrophic Lateral Sclerosis/genetics/physiopathology ; Phenotype ; Child ; *Guanine Nucleotide Exchange Factors/genetics ; Genotype ; Child, Preschool ; *Spastic Paraplegia, Hereditary/genetics/physiopathology ; Adolescent ; Pedigree ; Infant ; }, abstract = {INTRODUCTION: The Alsin Rho Guanine Nucleotide Exchange Factor (ALS2) gene encodes a protein alsin that functions as a guanine nucleotide exchange factor. The variations in ALS2 gene leads to degeneration of upper motor neurons of the corticospinal tract. The phenotypes resulting from variants in ALS2 gene are infantile-onset ascending hereditary spastic paralysis (IAHSP, OMIM # 607225), juvenile primary lateral sclerosis (JPLS, OMIM # 606353), and juvenile amyotrophic lateral sclerosis (JALS, OMIM # 205100). Our study objectives were to describe the clinical phenotype and genotype of children with an established diagnosis of ALS2 gene-related disorder.

METHODS: The clinical details, laboratory data, and genotype findings of children with an established diagnosis of ALS2 gene-related disorder were collected from the hospital electronic database after obtaining institutional review board approval.

RESULTS: One family with three affected siblings, a second family with a proband and an affected fetus, and a third family with two affected siblings with ALS2 gene variants were identified. IAHSP was diagnosed in all of our patients with variants in ALS2 gene. The clinical findings observed in our patients were insidious onset progressive spastic paraparesis, contractures, and dysarthria. Nonsense variants were observed in four patients while frameshift variant was observed in one family. Novel variants in ALS2 gene were identified in two unrelated families.

CONCLUSION: ALS2 mutation results in rare neurodegenerative disorders with the clinical spectrum encompassing IAHSP, JPLS, and JALS disorders. In view of allelic heterogeneity described in the literature, more research studies are needed for establishing genotype-phenotype correlation in patients with ALS2 gene-related disorder.}, } @article {pmid39423873, year = {2024}, author = {Thapa, R and Moglad, E and Afzal, M and Gupta, G and Bhat, AA and Hassan Almalki, W and Kazmi, I and Alzarea, SI and Pant, K and Singh, TG and Singh, SK and Ali, H}, title = {The role of sirtuin 1 in ageing and neurodegenerative disease: A molecular perspective.}, journal = {Ageing research reviews}, volume = {102}, number = {}, pages = {102545}, doi = {10.1016/j.arr.2024.102545}, pmid = {39423873}, issn = {1872-9649}, mesh = {Humans ; *Neurodegenerative Diseases/drug therapy/metabolism ; *Sirtuin 1/metabolism ; *Aging/metabolism/genetics ; Animals ; Oxidative Stress/physiology ; }, abstract = {Sirtuin 1 (SIRT1), an NAD+-dependent deacetylase, has emerged as a key regulator of cellular processes linked to ageing and neurodegeneration. SIRT1 modulates various signalling pathways, including those involved in autophagy, oxidative stress, and mitochondrial function, which are critical in the pathogenesis of neurodegenerative diseases. This review explores the therapeutic potential of SIRT1 in several neurodegenerative disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and Amyotrophic Lateral Sclerosis (ALS). Preclinical studies have demonstrated that SIRT1 activators, such as resveratrol, SRT1720, and SRT2104, can alleviate disease symptoms by reducing oxidative stress, enhancing autophagic flux, and promoting neuronal survival. Ongoing clinical trials are evaluating the efficacy of these SIRT1 activators, providing hope for future therapeutic strategies targeting SIRT1 in neurodegenerative diseases. This review explores the role of SIRT1 in ageing and neurodegenerative diseases, with a particular focus on its molecular mechanisms, therapeutic potential, and clinical applications.}, } @article {pmid39422938, year = {2024}, author = {Pappolla, MA and Wu, P and Fang, X and Poeggeler, B and Sambamurti, K and Wisniewski, T and Perry, G}, title = {Stem Cell Interventions in Neurology: From Bench to Bedside.}, journal = {Journal of Alzheimer's disease : JAD}, volume = {101}, number = {s1}, pages = {S395-S416}, doi = {10.3233/JAD-230897}, pmid = {39422938}, issn = {1875-8908}, mesh = {Humans ; Animals ; *Stem Cell Transplantation/methods/trends ; Nervous System Diseases/therapy ; Neurology/trends/methods ; Translational Research, Biomedical/trends ; Neural Stem Cells/transplantation ; }, abstract = {Stem cell therapies are progressively redefining the treatment landscape for a spectrum of neurological and age-related disorders. This review discusses the molecular and functional attributes of stem cells, emphasizing the roles of neural stem cells and mesenchymal stem cells in the context of neurological diseases such as stroke, multiple sclerosis, amyotrophic lateral sclerosis, traumatic brain injury, Parkinson's disease, and Alzheimer's disease. The review also explores the potential of stem cells in addressing the aging process. The paper analyzes stem cells' intrinsic properties of self-renewal, differentiation, and paracrine effects, alongside the importance of laboratory-modified stem cells like induced pluripotent stem cells and transgenic stem cells. Insights into disease-specific stem cell treatments are offered, reviewing both successes and challenges in the field. This includes the translational difficulties from rodent studies to human trials. The review concludes by acknowledging the uncharted territories that warrant further investigation, emphasizing the potential roles of stem cell-derived exosomes and indole-related molecules, and aiming at providing a basic understanding of stem cell therapies.}, } @article {pmid39420987, year = {2024}, author = {Sun, H and Tang, Q and Yan, X and Xie, W and Xu, Y and Zhang, W}, title = {Cathepsins and neurological diseases: a Mendelian randomization study.}, journal = {Frontiers in neuroscience}, volume = {18}, number = {}, pages = {1454369}, pmid = {39420987}, issn = {1662-4548}, abstract = {BACKGROUND: The causal relationship between cathepsins and neurological diseases remains uncertain. To address this, we utilized a two-sample Mendelian randomization (MR) approach to assess the potential causal effect of cathepsins on the development of neurological diseases.

METHODS: This study conducted a two-sample two-way MR study using pooled data from published genome-wide association studies to evaluate the relationship between 10 cathepsins (B, D, E, F, G, H, L2, O, S, and Z) and 7 neurological diseases, which included ischemic stroke, cerebral hemorrhage, Alzheimer's disease, Parkinson's disease, multiple sclerosis, amyotrophic lateral sclerosis, and epilepsy. The analysis employed various methods such as inverse variance weighting (IVW), weighted median, MR Egger regression, MR pleiotropy residual sum and outlier, Cochran Q statistic, and leave-one-out analysis.

RESULTS: We found a causal relationship between cathepsins and neurological diseases, including Cathepsin B and Parkinson's disease (IVW odds ratio (OR): 0.89, 95% confidence interval (CI): 0.83, 0.95, p = 0.001); Cathepsin D and Parkinson's disease (OR: 0.80, 95%CI: 0.68, 0.95, p = 0.012); Cathepsin E and ischemic stroke (OR: 1.05, 95%CI: 1.01, 1.09, p = 0.015); Cathepsin O and ischemic stroke (OR: 1.05, 95%CI: 1.01, 1.10, p = 0.021). Reverse MR analyses revealed that multiple sclerosis and Cathepsin E (OR: 1.05, 95%CI: 1.01, 1.10, p = 0.030). There is currently no significant relationship has been found between other cathepsins and neurological diseases.

CONCLUSION: Our study reveals a causal relationship between Cathepsins B, D, E, and O and neurological diseases, offering valuable insights for research aimed at improving the diagnosis and treatment of such conditions.}, } @article {pmid39419765, year = {2024}, author = {Johns, AE and Taga, A and Charalampopoulou, A and Gross, SK and Rust, K and McCray, BA and Sullivan, JM and Maragakis, NJ}, title = {Exploring P2X7 receptor antagonism as a therapeutic target for neuroprotection in an hiPSC motor neuron model.}, journal = {Stem cells translational medicine}, volume = {13}, number = {12}, pages = {1198-1212}, pmid = {39419765}, issn = {2157-6580}, mesh = {Humans ; *Motor Neurons/metabolism/drug effects ; *Receptors, Purinergic P2X7/metabolism ; *Induced Pluripotent Stem Cells/metabolism ; *Purinergic P2X Receptor Antagonists/pharmacology ; Animals ; Adenosine Triphosphate/metabolism ; Neuroprotection/drug effects ; Mice ; Rats ; }, abstract = {ATP is present in negligible concentrations in the interstitium of healthy tissues but accumulates to significantly higher concentrations in an inflammatory microenvironment. ATP binds to 2 categories of purine receptors on the surface of cells, the ionotropic P2X receptors and metabotropic P2Y receptors. Included in the family of ionotropic purine receptors is P2X7 (P2X7R), a non-specific cation channel with unique functional and structural properties that suggest it has distinct roles in pathological conditions marked by increased extracellular ATP. The role of P2X7R has previously been explored in microglia and astrocytes within the context of neuroinflammation, however the presence of P2X7R on human motor neurons and its potential role in neurodegenerative diseases has not been the focus of the current literature. We leveraged the use of human iPSC-derived spinal motor neurons (hiPSC-MN) as well as human and rodent tissue to demonstrate the expression of P2X7R on motor neurons. We extend this observation to demonstrate that these receptors are functionally active on hiPSC-MN and that ATP can directly induce death via P2X7R activation in a dose dependent manner. Finally, using a highly specific P2X7R blocker, we demonstrate how modulation of P2X7R activation on motor neurons is neuroprotective and could provide a unique pharmacologic target for ATP-induced MN death that is distinct from the role of ATP as a modulator of neuroinflammation.}, } @article {pmid39419433, year = {2025}, author = {Majumder, P and Hsu, TI and Hu, CJ and Huang, JK and Lee, YC and Hsieh, YC and Ahsan, A and Huang, CC}, title = {Potential role of solid lipid curcumin particle (SLCP) as estrogen replacement therapy in mitigating TDP-43-related neuropathy in the mouse model of ALS disease.}, journal = {Experimental neurology}, volume = {383}, number = {}, pages = {114999}, doi = {10.1016/j.expneurol.2024.114999}, pmid = {39419433}, issn = {1090-2430}, mesh = {Animals ; *Amyotrophic Lateral Sclerosis/drug therapy/metabolism ; Mice ; Female ; *Disease Models, Animal ; Male ; *DNA-Binding Proteins/metabolism/genetics ; *Estrogen Replacement Therapy/methods ; *Curcumin/pharmacology/administration & dosage/therapeutic use ; Mice, Transgenic ; Aromatase/metabolism ; Estradiol/pharmacology ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) was first identified in 1869, but it wasn't until the 2014 Ice Bucket Challenge that widespread attention was drawn to the disease. Since then, substantial research has been dedicated to developing treatments for ALS. Despite this, only three drugs - riluzole, edaravone and AMX0035, have been approved for clinical use, and they can only temporarily alleviate mild symptoms without significant disease modification or cure. Therefore, there remains a critical unmet need to identify disease modifying or curative therapies for ALS. The higher incidence and more severe progression of ALS and FTLD (frontotemporal lobar degeneration) observed in men and postmenopausal woman compared to young women suggests that sex hormones may significantly influence disease onset and progression. In both animal models and human clinical studies, 17β estradiol (E2) has been shown to delay and improve the outcomes of many neurodegenerative diseases. Here, we examined the role of TDP-43 in the regulation of estrogen-related enzymes, CYP19A1 and CYP3A4. In addition, we examined the impact of curcumin on the regulation of estrogen E2 levels and TDP-43-associated neuropathy as a potential therapeutic strategy for the treatment of FTLD and ALS.

METHODS: Prp-TDP-43[A315T] mice was used as a model of ALS/FTLD to examine the expression patterns of E2 and its biosynthesis and degradation enzymes, CYP19A1 and CYP3A4. Moreover, the molecular mechanisms and the potency of solid lipid curcumin particles (SLCP) as an E2 replacement therapy for TDP-43 associated neuropathy was analyzed. We further examined the survival rates and the pathological TDP43 patterns in female and male Prp-TDP-43[A315T] mice administrated with or without SLCP. In addition, the changed expression levels of enzymes corresponding to E2 biosynthesis and degradation in the spinal cord of female and male Prp-TDP-43[A315T] mice with or without SLCP were determined.

RESULTS: We found that in addition to E2, the expression patterns of CYP19A1 and CYP3A4 proteins differed between Prp-TDP-43[A315T] mice compared to wild-type control, suggesting that toxic phosphorylated TDP43 oligomers may disrupt the balance between CYP19A1 and CYP3A4 expression, leading to reduced estrogen biosynthesis and accelerated degradation. In addition, we found that oral administration of SLCP prolonged the survival rates in female Prp-TDP-43[A315T] mice and significantly reduced the pathological insoluble phosphorylated TDP-43 species. Furthermore, SLCP attenuated disease progression associated with TDP-43-related neuropathies through modulating estrogen biosynthesis and the activity of CYP450 enzymes.

CONCLUSIONS: Our results showed that Prp-TDP-43[A315T] mice exhibit altered estradiol levels. Moreover, we demonstrated the efficacy of SLCP as an estrogen replacement therapy in mitigating TDP-43-associated disease progression and pathogenesis. These findings suggest that SLCP could be a promising strategy to induce E2 expression for the treatment of ALS and FTLD.}, } @article {pmid39419034, year = {2025}, author = {Wijegunawardana, D and Nayak, A and Vishal, SS and Venkatesh, N and Gopal, PP}, title = {Ataxin-2 polyglutamine expansions aberrantly sequester TDP-43 ribonucleoprotein condensates disrupting mRNA transport and local translation in neurons.}, journal = {Developmental cell}, volume = {60}, number = {2}, pages = {253-269.e5}, pmid = {39419034}, issn = {1878-1551}, support = {R01 NS122907/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; *Peptides/metabolism/genetics ; *RNA, Messenger/metabolism/genetics ; *Ataxin-2/metabolism/genetics ; Mice ; *DNA-Binding Proteins/metabolism/genetics ; Rats ; *Motor Neurons/metabolism ; *Ribonucleoproteins/metabolism ; *Protein Biosynthesis ; *RNA Transport ; *Neurons/metabolism ; Axons/metabolism ; Humans ; Amyotrophic Lateral Sclerosis/metabolism/genetics ; *Nerve Tissue Proteins/metabolism/genetics ; }, abstract = {Altered RNA metabolism and misregulation of transactive response DNA-binding protein of 43 kDa (TDP-43), an essential RNA-binding protein (RBP), define amyotrophic lateral sclerosis (ALS). Intermediate-length polyglutamine (polyQ) expansions of Ataxin-2, a like-Sm (LSm) RBP, are associated with increased risk for ALS, but the underlying biological mechanisms remain unknown. Here, we studied the spatiotemporal dynamics and mRNA regulatory functions of TDP-43 and Ataxin-2 ribonucleoprotein (RNP) condensates in rodent (rat) primary cortical neurons and mouse motor neuron axons in vivo. We report that Ataxin-2 polyQ expansions aberrantly sequester TDP-43 within RNP condensates and disrupt both its motility along the axon and liquid-like properties. We provide evidence that Ataxin-2 governs motility and translation of neuronal RNP condensates and that Ataxin-2 polyQ expansions fundamentally perturb spatial localization of mRNA and suppress local translation. Overall, our results support a model in which Ataxin-2 polyQ expansions disrupt stability, localization, and/or translation of critical axonal and cytoskeletal mRNAs, particularly important for motor neuron integrity.}, } @article {pmid39418491, year = {2025}, author = {Kumar, R and Ghai, S and Finelli, A and Klotz, L and Kinnaird, A and Mannas, M and Bhindi, B and Sanchez-Salas, R and Anidjar, M and Ahmad, A and Chin, J and Inman, B and Perlis, N}, title = {The use of focal therapy for the treatment of prostate cancer in Canada Where are we, how did we get here, and where are we going?.}, journal = {Canadian Urological Association journal = Journal de l'Association des urologues du Canada}, volume = {19}, number = {2}, pages = {63-72}, pmid = {39418491}, issn = {1911-6470}, abstract = {INTRODUCTION: Focal therapy is an emerging treatment for localized prostate cancer (PCa). The objectives of this review were to: 1) review how focal therapies are regulated and approved; 2) summarize the scope and quality of the literature regarding safety, efficacy, and side-effects; and 3) outline ongoing clinical trials of focal therapy in Canada.

METHODS: Using the PRISMA framework for scoping reviews, we searched PubMed, Embase, and Cochrane from 2021-2024, complementing Hopstaken et al's search up to 2020. We focused on studies reporting functional and oncologic outcomes. Additionally, we examined the FDA database for regulatory details and ongoing trials in Canada via ClinicalTrials.gov.

RESULTS: FDA approval for prostate tissue ablation was granted to high-intensity focused ultrasound (HIFU) in 2015 via the de novo pathway; other therapies followed the 510(k) route, citing equivalence to predicate devices. Most studies are in early stages, primarily single-arm, prospective cohort designs. Oncologic outcomes like cancer detection and survival rates, alongside functional data, such as adverse events and erectile function, were assessed. Recurrence-free survival at 48 months ranged from 58-92%, pad-free rates were greater than 95%, and rates of new-onset erectile dysfunction were variable, ranging from no change to 50%. Rates of serious adverse events were low, ranging from 0-14%. Three Canadian clinical trials are actively enrolling participants, and five private clinics were found offering private HIFU, irreversible electroporation, or transurethral ultrasound ablation.

CONCLUSIONS: Focal therapy technologies have gained regulatory approval for prostate tissue ablation, and aside from provincial support for cryoablation in Alberta, are available to Canadians through private payment or clinical trials. Many studies demonstrate promising cancer control and impressive functional outcomes but are limited by their short followup and lack of comparator group. Clinical trial or registry participation should be prioritized to ensure an evidence-based integration into current prostate cancer treatment approaches.}, } @article {pmid39416141, year = {2024}, author = {Winkelsas, A and Apfel, A and Johnson, B and Harmison, G and Li, D and Cheung, V and Grunseich, C}, title = {Allele-specific silencing of a dominant SETX mutation in familial amyotrophic lateral sclerosis type 4.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {39416141}, issn = {2692-8205}, support = {R21 ES034919/ES/NIEHS NIH HHS/United States ; }, abstract = {Amyotrophic lateral sclerosis 4 (ALS4) is an autosomal dominant motor neuron disease that is molecularly characterized by reduced R-loop levels and caused by pathogenic variants in senataxin (SETX). SETX encodes an RNA/DNA helicase that resolves three-stranded nucleic acid structures called R-loops. Currently, there are no disease-modifying therapies available for ALS4. Given that SETX is haplosufficient, removing the product of the mutated allele presents a potential therapeutic strategy. We designed a series of siRNAs to selectively target the RNA transcript from the ALS4 allele containing the c.1166T>C mutation (p.Leu389Ser). Transfection of HEK293 cells with siRNA and plasmids encoding either wild-type or mutant (Leu389Ser) epitope tagged SETX revealed that three siRNAs specifically reduced mutant SETX protein levels without affecting the wild-type SETX protein. In ALS4 primary fibroblasts, siRNA treatment silenced the endogenous mutant SETX allele, while sparing the wild-type allele, and restored R-loop levels in patient cells. Our findings demonstrate that mutant SETX, differing from wild-type by a single nucleotide, can be effectively and specifically silenced by RNA interference, highlighting the potential of allele-specific siRNA as a therapeutic approach for ALS4.}, } @article {pmid39416104, year = {2024}, author = {Gunner, G and Basu, H and Lu, Y and Bergstresser, M and Neel, D and Choi, SY and Chiu, IM}, title = {Gasdermin D is activated but does not drive neurodegeneration in SOD1 [G93A] model of ALS: Implications for targeting pyroptosis.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2024.10.10.617609}, pmid = {39416104}, issn = {2692-8205}, support = {T32 AG000222/AG/NIA NIH HHS/United States ; }, abstract = {Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive motor neuron loss, microgliosis, and neuroinflammation. While pyroptosis, an inflammatory form of programmed cell death, has been implicated in ALS, the specific role of Gasdermin D (GSDMD) - the primary executioner of pyroptosis - remains unexplored. In this study, we examined the function of GSDMD in the well-established SOD1 [G93A] mouse model of ALS. Our results showed robust GSDMD activation in the spinal cords of SOD1 [G93A] animals across two strain backgrounds, with elevated expression in Iba1+ microglia. To explore its role in disease progression, we bred B6.SOD1 [G93A] mice onto a GSDMD - deficient background. In comparing SOD1 [G93A] ; Gsdmd +/+ and SOD1 [G93A] ; Gsdmd -/- mice, we found that Gsdmd loss did not affect disease onset, weight loss, or grip strength decline in either male or female animals. Notably, GSDMD deficiency resulted in a modest but statistically significant increase in mortality in SOD1 [G93A] mice. Moreover, GSDMD absence had minimal impact on astrogliosis, microgliosis and motor neuron loss. These findings show that while GSDMD is activated in the ALS mouse model, its loss does not mitigate key ALS behavioral phenotypes, gliosis or motor neuron loss. This study provides insights into the potential therapeutic relevance of targeting pyroptosis and inflammatory pathways in ALS.}, } @article {pmid39415649, year = {2024}, author = {Kim, Y and O, JH and Cho, H and Ye, S}, title = {Recognized cases of amyotrophic lateral sclerosis in automobile workers by the Korean Epidemiologic Investigation Evaluation Committee.}, journal = {Annals of occupational and environmental medicine}, volume = {36}, number = {}, pages = {e28}, pmid = {39415649}, issn = {2052-4374}, abstract = {BACKGROUND: Three automobile company workers (one from Factory D and two from Factory E) were diagnosed with amyotrophic lateral sclerosis. The Korean Epidemiologic Investigation and Evaluation Committee determined that there is considerable scientific evidence supporting the association between amyotrophic lateral sclerosis and combined exposure to heavy metals, organic solvents, and diesel exhaust at the manufacturing plant.

CASE PRESENTATION: Patient A, who primarily engaged in engine processing and completed vehicle inspection at Factory D, was exposed to considerable amounts of heavy metals and organic solvents during medium- and large-engine processing, welding, and painting for over 23 years. Additionally, the patient was likely exposed to diesel exhaust for 33 years from forklifts delivering engines in the workshop. Patients B and C, who were responsible for engine assembly, ignition testing, and engine shipment at Factory E since around 1990, were exposed to lead and benzene from gasoline during engine ignition tests in the engine department for 15 and 16 years, respectively. They also encountered welding fumes, heavy metals, and organic solvents during welding and painting tasks. In addition, Patients B and C were continuously exposed to diesel exhaust from logistics vehicles on standby during work hours for 25 and 30 years, respectively.

CONCLUSIONS: Although the specific level of lead exposure causing amyotrophic lateral sclerosis remains undetermined, numerous studies have consistently reported a relationship between lead exposure and disease development. Limited evidence suggests that exposure to organic solvents and diesel exhaust may increase the risk of amyotrophic lateral sclerosis. Therefore, the Epidemiological Investigation and Evaluation Committee concluded that the three patients' work-related exposure to heavy metals, organic solvents, and diesel exhaust is significantly supported by scientific evidence as a cause of their amyotrophic lateral sclerosis.}, } @article {pmid39415277, year = {2024}, author = {Abdelnaby, R and Shabib, AS and El Din Moawad, MH and Salem, T and Wagih Youssef Awad, M and Awad, PD and Maallem, I and Atwan, H and Rabie, SA and Mohamed, KA and Abdelmageed, H and Karkour, AM and Elsayed, M and Cartwright, MS}, title = {Nerve ultrasound in amyotrophic lateral sclerosis: systematic review and meta-analysis.}, journal = {Neurological research and practice}, volume = {6}, number = {1}, pages = {47}, pmid = {39415277}, issn = {2524-3489}, abstract = {BACKGROUND/ AIM: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease affecting upper and lower motor neurons, causing progressive atrophy of muscles, hypertonia, and paralysis. This study aimed to evaluate the current evidence and effectiveness of ultrasound in investigating nerve cross-sectional area (CSA) of peripheral nerves, vagus and cervical roots in those with ALS compared with healthy controls and to pool the CSA measurements.

METHODS: A systematic search was conducted on Cochrane, Clarivate Web of Science, PubMed, Scopus, and Embase for the mesh terms nerve, ultrasonography, and amyotrophic lateral sclerosis. A quality assessment was performed using the New-Ottawa scale. In addition, a double-arm meta-analysis using Review Manager 5 software version 5.4 was performed.

RESULTS: From the seventeen studies included in this review, the overall mean difference showed that individuals with ALS had a significantly smaller CSA in comparison to healthy controls for median, ulnar, C6 root, and phrenic nerves. However, no significant difference in the CSA was found in radial, vagal, sural, and tibial nerves.

DISCUSSION: This study confirmed results of some of the included studies regards the anatomic sites, where nerve atrophy in ALS could be detected to potentially support the diagnosis of ALS. However, we recommend further large, prospective studies to assess the diagnostic value of these anatomical sites for the diagnosis of ALS.

CONCLUSIONS: Our findings confirmed specific anatomic sites to differentiate ALS patients from healthy controls through ultrasound. However, these findings cannot be used to confirm the ALS diagnosis, but rather assist in differentiating it from other diagnoses.

TRIAL REGISTRATION: Retrospectively registered on July 30th 2024 in PROSPERO (PROSPERO (york.ac.uk)) with ID574702.}, } @article {pmid39414899, year = {2024}, author = {Kawata, S and Seki, S and Nishiura, A and Kitaoka, Y and Iwamori, K and Fukada, SI and Kogo, M and Tanaka, S}, title = {Preservation of masseter muscle until the end stage in the SOD1G93A mouse model for ALS.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {24279}, pmid = {39414899}, issn = {2045-2322}, mesh = {Animals ; *Amyotrophic Lateral Sclerosis/pathology/genetics ; *Masseter Muscle/pathology ; *Disease Models, Animal ; Mice ; Superoxide Dismutase-1/genetics/metabolism ; Mice, Transgenic ; Satellite Cells, Skeletal Muscle/pathology/metabolism ; Motor Neurons/pathology/metabolism ; Male ; }, abstract = {Amyotrophic lateral sclerosis (ALS) progressively impairs motor neurons, leading to muscle weakness and loss of voluntary muscle control. This study compared the effects of SOD1 mutation on masticatory and limb muscles from disease onset to death in ALS model mice. Notably, limb muscles begin to atrophy soon after ALS-like phenotype appear, whereas masticatory muscles maintain their volume and function in later stages. Our analysis showed that, unlike limb muscles, masticatory muscles retain their normal structure and cell makeup throughout most of the disease course. We found an increase in the number of muscle satellite cells (SCs), which are essential for muscle repair, in masticatory muscles. In addition, we observed no reduction in the number of muscle nuclei and no muscle fibre-type switching in masticatory muscles. This indicates that masticatory muscles have a higher resistance to ALS-related damage than limb muscles, likely because of differences in cell composition and repair mechanisms. Understanding why masticatory muscles are less affected by ALS could lead to the development of new treatments. This study highlights the importance of studying different muscle groups in ALS to clarify disease aetiology and mechanisms.}, } @article {pmid39413009, year = {2024}, author = {Ralbovsky, NM and Zhang, Y and Williams, DM and McKelvey, CA and Smith, JP}, title = {Machine Learning and Hyperspectral Imaging for Analysis of Human Papillomaviruses (HPV) Vaccine Self-Healing Particles.}, journal = {Analytical chemistry}, volume = {96}, number = {43}, pages = {17118-17127}, doi = {10.1021/acs.analchem.4c02327}, pmid = {39413009}, issn = {1520-6882}, mesh = {*Papillomavirus Vaccines/immunology ; *Machine Learning ; Humans ; Vaccines, Virus-Like Particle ; Human Papillomavirus Viruses ; }, abstract = {Human papillomaviruses (HPV) are known to cause a variety of diseases, including cervical cancer and genital warts. HPV is a highly prevalent virus and is considered the most common sexually transmitted disease. Because of the risks associated with HPV, Gardasil, a quadrivalent recombinant vaccine, was developed by Merck & Co., Inc., Rahway, NJ, USA, and approved by the Food and Drug Administration (FDA) in 2006. The second generation of the vaccine, Gardasil9, was subsequently approved by the FDA in 2014, providing significant protection against HPV. The HPV vaccine may be given as 2 or 3 doses; however, vaccine administration as a single dose with a sustained release mechanism may potentially offer benefits to meet emerging health needs. To explore this, HPV vaccines were formulated within microporous self-healing particles (SHPs) to enable potential controlled release of HPV virus-like particle (VLP) antigen. Machine learning, in the form of multivariate curve resolution-alternating least-squares (MCR-ALS), with Raman hyperspectral imaging was used to determine the molecular identity and spatial distribution of all relevant species within this HPV vaccine formulation. The results indicate that machine learning with Raman hyperspectral imaging was able to spatially resolve HPV VLP antigens within SHP vaccines for the first time, providing crucial information necessary for vaccine development.}, } @article {pmid39412921, year = {2024}, author = {Bahador, M and Soltaninejad, S and Mobasheri, M}, title = {Correlation of new two-dimensional geometrical parameters to lung and heart dose-volume parameters in breast cancer radiation therapy.}, journal = {Journal of cancer research and therapeutics}, volume = {20}, number = {5}, pages = {1570-1577}, doi = {10.4103/jcrt.jcrt_2351_23}, pmid = {39412921}, issn = {1998-4138}, mesh = {Humans ; Female ; *Heart/radiation effects/diagnostic imaging ; *Radiotherapy Dosage ; *Radiotherapy Planning, Computer-Assisted/methods ; *Lung/radiation effects/diagnostic imaging/pathology ; *Breast Neoplasms/radiotherapy/pathology ; *Organs at Risk/radiation effects ; Tomography, X-Ray Computed/methods ; ROC Curve ; Middle Aged ; }, abstract = {OBJECTIVE: To develop new two-dimensional geometric parameters for pulmonary and cardiac dose estimation in left-sided breast cancer radiation therapy without dose-volume histogram (DVH).

METHODS: On the CT image of 90 patients with left breast cancer, treatment planning was performed using two opposed tangent fields with/without supraclavicular. The field-in-field technique and 6MV photons were used. From DVH dosimetric parameters of mean dose, Vx (x (Gy) =5, 10, 15, 20, 30, 40, 50) were calculated, and from heart and lung outlines on the beam's eye view, new geometric parameters of percent of lung area in tangent and supraclavicular fields (%area of the lung in the tangent (ALT), %ALS) and percent of heart in tangent field (%area of the heart in the tangent (AHT)) were measured. Correlation, regression, and diagnostic performance by receiver operating characteristic curve (ROC) were investigated for statistical analysis.

RESULTS: The Pearson coefficient between %ALT and Vx (x = 10, 15, 20, 30, 40) show strong correlation in patient treatment with only opposed tangents (>0.85) and weaker in treatment by opposed tangents with supraclavicular (0.56-0.88), the %ALS indicate weak correlation (<0.5) and %AHT show strong correlation (0.93-0.98). The regression analysis shows a positive relation between %ALT and mean dose (R2 = 0.8), V20Gy (R2 = 0.9) in the lung (tangent treatment), and between %AHT and mean dose (R2 = 0.9), V20Gy (R2 = 1.0) in the heart. The ROC analysis shows by %ALT <20.3 for treatment by just opposed fields, %ALT <22.1% for treatment tangents with supra, and %AHT <11.6%, practical lung and heart dose constraints are addressed.

CONCLUSION: The proposed geometric parameters could replace previous one-dimensional maximum and central distances for predicting doses to lung and heart.

ADVANCES IN KNOWLEDGE: This study presents simple geometric parameters that could estimate pulmonary and cardiac dose in left breast cancer treatment from a 2D radiograph.}, } @article {pmid39412565, year = {2024}, author = {Sangari, S and Lackmy-Vallee, A and Preuilh, A and Peyre, I and Pradat, PF and Marchand-Pauvert, V}, title = {Synaptic dynamics linked to widespread elevation of H-reflex before peripheral denervation in amyotrophic lateral sclerosis.}, journal = {Journal of neurophysiology}, volume = {132}, number = {5}, pages = {1541-1560}, doi = {10.1152/jn.00144.2024}, pmid = {39412565}, issn = {1522-1598}, support = {VMarchand/2013//ARSLA/ ; DdT1 2015- 2; CTL/SS/2016-0029/no 16597//AFM-Telethon/ ; FTL AAP7/2015//Fondation Thierry Latran (Thierry Latran Foundation)/ ; }, mesh = {Humans ; *H-Reflex/physiology ; *Amyotrophic Lateral Sclerosis/physiopathology ; Male ; Female ; Middle Aged ; *Evoked Potentials, Motor/physiology ; *Muscle, Skeletal/physiopathology/physiology ; Aged ; Adult ; Excitatory Postsynaptic Potentials/physiology ; Riluzole/pharmacology ; Motor Neurons/physiology ; }, abstract = {Changes in Hoffmann reflex (H-reflex) exhibit heterogeneity among patients with amyotrophic lateral sclerosis (ALS), likely due to phenotype diversity. Current knowledge primarily focuses on soleus H-reflex, which may demonstrate an initial increase before subsequent decline throughout the disease course. The main objective was to investigate other muscles, to determine whether H-reflex changes could be associated with patient phenotype (onset site, functional disabilities). Additional experiments were performed to elucidate the neurophysiological mechanisms underlying H-reflex modifications. In age- and sex-matched groups of control subjects and patients, we compared H-reflex recruitment curves in soleus, quadriceps, and forearm flexors. Additionally, we examined H-reflex and motor evoked potential (MEP) recruitment curves in quadriceps. Last, to assess potential changes in monosynaptic excitatory postsynaptic potentials (EPSPs) of both peripheral and cortical origins, we analyzed peristimulus time histograms (PSTHs) and peristimulus frequencygrams (PSFs) of single motor units, along with H-reflex occurrence after paired-pulse stimuli. The ratio between maximal amplitudes of H-reflex and direct motor response increased in all muscles, irrespective of disease onset, and was found positively correlated with exaggerated osteotendinous reflexes and spasticity but depressed in patients on riluzole. This finding was accompanied by a reduction in MEP size and no changes in PSTH, PSF, and paired-pulse H-reflex probability. It is speculated that spinal interneurons may compensate for potential depression of monosynaptic EPSPs in ALS. From a clinical perspective, although the added value of H-reflex to osteotendinous reflex evaluation may be limited, it can serve as a valuable quantitative biomarker of pyramidal dysfunction in clinical trials.NEW & NOTEWORTHY Without significant evidence of peripheral denervation, H-reflex enhancement appears to be a widespread phenomenon, regardless of disease onset site. This increase is likely associated with a decrease in inhibitory control over presynaptic transmission of the synapse between muscle group Ia afferents and motoneurons. Although the link to exaggerated osteotendinous reflexes and spasticity implies a restricted role in identifying a pyramidal syndrome, its quantitative aspect positions the H-reflex as a valuable biomarker in clinical trials.}, } @article {pmid39412227, year = {2025}, author = {Mascías Cadavid, J and Radakovic, R and Radakovic, C and Moran Benito, Y and Marín Esteban, S and Rodríguez-Santos, F and Salas Campos, T}, title = {Spanish adaptation of the Rasch-Built Overall Amyotrophic Lateral Sclerosis Disability Scale (ROADS).}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {26}, number = {3-4}, pages = {375-378}, doi = {10.1080/21678421.2024.2416665}, pmid = {39412227}, issn = {2167-9223}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/psychology/physiopathology ; Female ; Male ; Middle Aged ; *Disability Evaluation ; Aged ; Reproducibility of Results ; Psychometrics/methods ; Spain ; Adult ; Severity of Illness Index ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is characterized functional decline, traditionally measured by the ALS Functional Rating Scale-Revised (ALSFRS-R). The Rasch-Built Overall Amyotrophic Lateral Sclerosis Disability Scale (ROADS) is an alternative comprehensive, detailed functional disability measure for people with ALS (pwALS), not yet translated to Spanish. The aim of this study was to translate and validate the Spanish ROADS. 53 Spanish speaking pwALS were recruited. They completed the ALSFRS-R and Spanish ROADS. Reliability (internal consistency, intra-class correlation) and validity (ALSFRS-R total and item-total correlations) were determined. The Spanish ROADS internal consistency reliability was excellent (Cronbach's standardized alpha = 0.94), the test-retest reliability intra-class correlation value was 0.93. There was a strong significant correlation between the Spanish ROADS and ALSFRS-R totals (rs(52) = .89, p < .001). Additionally, the ALSFRS-R subscales and ROADS items correlations showed domain-to-item specific expected significant correlations. The Spanish ROADS is a psychometrically robust, valid and reliable measure for quantifying functional disability for pwALS.}, } @article {pmid39411168, year = {2024}, author = {An, D and Han, J and Fang, P and Bu, Y and Ji, G and Liu, M and Deng, J and Song, X}, title = {Evidence for the potential role of m6A modification in regulating autophagy in models of amyotrophic lateral sclerosis.}, journal = {CytoJournal}, volume = {21}, number = {}, pages = {33}, pmid = {39411168}, issn = {0974-5963}, abstract = {OBJECTIVE: Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease. Research indicates that N6-methyladenosine (m6A) modification plays a crucial role in cellular autophagy during ALS development. This study investigates the role of autophagy in ALS, with a focus on the effect of messenger ribonucleic acid m6A methylation modification on disease progression.

MATERIAL AND METHODS: We compared m6A levels and regulatory molecule expressions in transgenic superoxide dismutase (SOD1)-G93A and non-transgenic mice, categorized into end-stage and control groups, using quantitative polymerase chain reaction and Western blotting. The NSC-34 cell line, which was modified to model ALS, enabled the investigation of apoptosis, autophagy, and autophagy disruption through terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labeling assays, Western blotting, and fluorescent staining.

RESULTS: Our findings indicate significantly elevated m6A methylation levels in ALS mice (0.262 ± 0.005) compared with the controls (0.231 ± 0.003) and in the ALS model cells (0.242±0.005) relative to those belonging to the wild-type control group (0.183 ± 0.007). Furthermore, the proteins involved in m6A RNA modification differed between groups, which suggest impaired autophagy flux in the ALS models.

CONCLUSION: These results suggest that m6A methylation may accelerate ALS progression through the disruption of autophagic processes. Our study underscores the role of m6A methylation in the pathology of ALS and proposes the targeting of m6A methylation as a potential therapeutic strategy for disease treatment. Although this study primarily used transgenic SOD1-G93A mice and NSC-34 cell models to investigate ALS pathology, potential differences in disease mechanisms between animal models and humans must be considered. Although a correlation was detected between m6A methylation levels and autophagy disruption in ALS, the study primarily established an association rather than provided detailed mechanistic insights.}, } @article {pmid39410995, year = {2024}, author = {Zaninotto, AL and Makary, MM and Rowe, HP and Eshghi, M and Tseng, CJ and Chan, J and Zürcher, NR and Hooker, J and Lewis, A and Keegan, M and Gifford, RF and Green, JR and Babu, S}, title = {Speech motor impairment in ALS is associated with multiregional cortical thinning beyond primary motor cortex.}, journal = {Frontiers in neurology}, volume = {15}, number = {}, pages = {1451177}, pmid = {39410995}, issn = {1664-2295}, support = {K23 DC019179/DC/NIDCD NIH HHS/United States ; }, abstract = {INTRODUCTION: Cortical thinning is well-documented in individuals with amyotrophic lateral sclerosis (ALS), yet its association with speech deterioration remains understudied. This study characterizes anatomical changes in the brain within the context of speech impairment patterns in individuals with ALS, providing insight into the disease's multiregional spread and biology.

METHODS: To evaluate patterns of cortical thickness in speakers with ALS with and without functional speech changes compared to healthy controls (HCs) using whole-brain and region of interest (ROI) analyses. Forty individuals with ALS and 22 HCs underwent a T1-weighted 3-Tesla magnetic resonance imaging (MRI). Individuals with ALS were divided into two groups based on the preserved speech [ps-ALS] (n = 18) or deteriorated speech [ds-ALS] (n = 22) as measured by the ALSFRSF-R speech subscore (=4 or <4 points, respectively). Sixteen a priori-defined and automatically segmented cortical and subcortical brain ROIs were selected based on their previously documented roles in speech production. Two cortical thickness analyses were performed: (1) group-level whole-brain surface-based analyses and (2) group-level ROI analyses. A case study of 6 ALS individuals examined the cortical thickness, and their speech was characterized using quantitative and qualitative measures.

RESULTS: Based on the group-level whole-brain surface-based analyses, the ds-ALS group demonstrated significant cortical thinning compared to HCs in the left primary motor and somatosensory cortices and the right inferior parietal lobe with its adjacent lateral occipital cortical regions. The ps-ALS group demonstrated no significant cortical thinning compared to HCs. Based on the group-level ROI analyses, the ds-ALS group demonstrated significant cortical thinning compared to HCs in bilateral middle motor cortices, right posterior dorsal premotor cortex, and left anterior cingulate cortex. The case study analysis revealed that ALS speakers with speech features characteristic of spastic dysarthria exhibited cortical thinning, while those with speech features characteristic of flaccid dysarthria did not.

DISCUSSION: Individuals with ALS have anatomical changes involving multiregional neocortical areas beyond the primary motor cortex that may manifest as subjective (i.e., clinical judgment) and objective (i.e., speaking rate) changes in speech production. Further longitudinal work in ALS is needed to better understand the link between MRI cortical thickness changes and bulbar dysfunction.}, } @article {pmid39408720, year = {2024}, author = {Du, X and Dong, Q and Zhu, J and Li, L and Yu, X and Liu, R}, title = {Rutin Ameliorates ALS Pathology by Reducing SOD1 Aggregation and Neuroinflammation in an SOD1-G93A Mouse Model.}, journal = {International journal of molecular sciences}, volume = {25}, number = {19}, pages = {}, pmid = {39408720}, issn = {1422-0067}, support = {XDB39050600//Strategic Priority Research Program of Chinese Academy of Sciences/ ; 82150107//National Natural Science Foundation of China/ ; }, mesh = {Animals ; *Rutin/pharmacology/therapeutic use ; *Amyotrophic Lateral Sclerosis/drug therapy/metabolism/pathology/genetics ; Mice ; *Superoxide Dismutase-1/metabolism/genetics ; *Disease Models, Animal ; *Mice, Transgenic ; *Spinal Cord/drug effects/metabolism/pathology ; Motor Neurons/drug effects/metabolism/pathology ; Neuroprotective Agents/pharmacology/therapeutic use ; Neuroinflammatory Diseases/drug therapy/metabolism ; Humans ; Protein Aggregation, Pathological/drug therapy/metabolism ; Male ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by the progressive loss of motor neurons, with limited effective treatments. Recently, the exploration of natural products has unveiled their potential in exerting neuroprotective effects, offering a promising avenue for ALS therapy. In this study, the therapeutic effects of rutin, a natural flavonoid glycoside with neuroprotective properties, were evaluated in a superoxide dismutase 1 (SOD1)-G93A mouse model of ALS. We showed that rutin reduced the level of SOD1 aggregation and diminished glial cell activation in spinal cords and brainstems, resulting in significantly improved motor function and motor neuron restoration in SOD1-G93A mice. Our findings indicated that rutin's multi-targeted approach to SOD1-related pathology makes it a promising candidate for the treatment of ALS.}, } @article {pmid39408173, year = {2024}, author = {Rolling, J and Fath, M and Zanfonato, T and Durpoix, A and Mengin, AC and Schröder, CM}, title = {EMDR-Teens-cPTSD: Efficacy of Eye Movement Desensitization and Reprocessing in Adolescents with Complex PTSD Secondary to Childhood Abuse: A Case Series.}, journal = {Healthcare (Basel, Switzerland)}, volume = {12}, number = {19}, pages = {}, pmid = {39408173}, issn = {2227-9032}, abstract = {Background: Mental healthcare for children and adolescents with a history of childhood abuse constitutes a major public health issue. Indeed, abuse exposes children to severe and complex post-traumatic stress disorder (cPTSD) but also to neurodevelopmental and psychological repercussions impacting the developmental trajectory. Trauma-focused care is essential to avoid the chronicization of symptoms and disorders. Objective: The aim of this prospective case series study was to investigate the efficacy of eye movement desensitization and reprocessing (EMDR) on complex post-traumatic symptoms and associated psychiatric disorders in adolescents with a history of abuse. Method: Twenty-two adolescents, aged 12 to 17, who had been abused during childhood were included. All adolescents met ICD-11 criteria for complex PTSD. Subjective measures of PTSD and associated psychiatric disorders were taken before (T0) and after 3 months of EMDR therapy (T1). Results: The average PTSD symptom score on the CPTS-RI significantly decreased from 40.2 to 34.4 after EMDR, indicating improvement in post-traumatic symptoms. A significant decrease in the average depression score (CDI from 18.2 at T0 to 10.6 at T1), anxiety score (R-CMAS from 21.3 at T0 to 13.3 at T1), emotional regulation score (ALS from 29 at T0 to 10.8 at T1), insomnia score (ISI from 18.5 at T0 to T1 of 9.2 at T1), and harmful use of alcohol and drugs score (ADOSPA from 2.3 at T0 to 0.3 at T1) was observed after EMDR therapy, as well as an increase in quality of life (CBCL 4-16 score from 57.9 at T0 to 77.4 at T1). Conclusions: The results of this study are encouraging and suggest that EMDR may be effective in the symptom management reducing post-traumatic symptoms and certain comorbid disorders frequently seen in adolescents who have experienced childhood abuse. Further research is needed on adolescent populations suffering from cPTSD (e.g., randomized controlled trials with control groups and other therapies or evaluating the action of the different phases of the study).}, } @article {pmid39407861, year = {2024}, author = {Proaño, B and Cuerda-Ballester, M and Daroqui-Pajares, N and Del Moral-López, N and Seguí-Sala, F and Martí-Serer, L and Calisaya Zambrana, CK and Benlloch, M and de la Rubia Ortí, JE}, title = {Clinical and Sociodemographic Factors Related to Amyotrophic Lateral Sclerosis in Spain: A Pilot Study.}, journal = {Journal of clinical medicine}, volume = {13}, number = {19}, pages = {}, pmid = {39407861}, issn = {2077-0383}, support = {2021-203-003//Catholic University of Valencia San Vicente Mártir/ ; }, abstract = {Background: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease of unknow etiology. Male sex is a well stablished risk factor, but other factors such as early and adult life expositions show contradictory evidence. Aim: to explore the link of clinical, sociodemographic, and occupational factors with ALS patients in Spain and the impact of these factors in functionality. Methods: A cross-sectional study was conducted with ALS patients and healthy controls. Registered variables were smoking, arterial hypertension, diabetes mellitus type 2, previous cancer to reproductive organs or breast, occupational exposure, and early life exposures. Functionality in ALS patients was compared according to each exposure. Results: The ALS group consisted of 59 participants and the control group of 90 participants. ALS patients showed a significant association with previous cancer (p = 0.011), occupational exposure (p < 0.001), and older siblings (p = 0.029). ALS patients presented significant differences in BMI according to hypertension and older-sibling factors. Moreover, respiratory function was affected in patients with previous cancer (p = 0.031). Conclusions: Occupational exposure and previous cancer to reproductive organs or breast could be linked to ALS patients. In addition, hypertension and previous cancer could affect their BMI and respiratory function. Other factors such as longer smoking periods and exposition to older siblings could also characterize ALS patients.}, } @article {pmid39407580, year = {2024}, author = {Forleo, T and Giannossa, LC and De Juan Capdevila, A and Lagioia, G and Mangone, A}, title = {Hats Off to Modeling! Profiling Early Synthetic Dyes on Historic Woolen Samples with ATR-FTIR Spectroscopy and Multivariate Curve Resolution-Alternating Least Square Algorithm.}, journal = {Molecules (Basel, Switzerland)}, volume = {29}, number = {19}, pages = {}, pmid = {39407580}, issn = {1420-3049}, abstract = {This research focuses on analyzing wool samples dyed with synthetic dyes from the early 20th century. A methodology to identify and distinguish wool fibers dyed with azo, triphenylmethane, and xanthene dyes, which are no longer in use, using the ATR-FTIR spectra, is presented. Firstly, the dataset was subjected to PCA, which revealed the similarities and differences among the samples, illustrating a distribution pattern based on dye classes. MCR-ALS was employed to extract the spectral profiles of the dyed fibers, thereby enhancing the efficacy of the analytical techniques and extracting the comprehensive information from a single instrument. The combination of ATR-FTIR spectroscopy with chemometric methods, such as PCA and MCR-ALS, has proven to be an effective strategy for identifying and differentiating wool fibers dyed with early azo, triphenylmethane, and xanthene dyes. This approach has demonstrated particular effectiveness in enabling rapid analysis without requiring sampling or pretreatment. Moreover, the analysis is supported by thorough bibliographic research on these no longer used colorants. In order to maximize the potential of non-destructive spectroscopic techniques, such as ATR-FTIR, the approach used has proven to be crucial. This study underscores how chemometric techniques expand the capabilities of spectroscopy, extracting extensive information from a single instrument and aligning with the goals of cultural heritage analysis.}, } @article {pmid39406675, year = {2025}, author = {Schilfarth, P and Réginault, T and Mathis, S and Le Masson, G and Pillet, O and Grassion, L}, title = {Changes in Non-invasive Ventilation Compliance in Patients With Amyotrophic Lateral Sclerosis: A Post-hoc Analysis.}, journal = {Archivos de bronconeumologia}, volume = {61}, number = {1}, pages = {47-49}, doi = {10.1016/j.arbres.2024.09.003}, pmid = {39406675}, issn = {1579-2129}, } @article {pmid39406341, year = {2024}, author = {López-Royo, T and Moreno-Martínez, L and Zaragoza, P and García-Redondo, A and Manzano, R and Osta, R}, title = {Differentially expressed lncRNAs in SOD1[G93A] mice skeletal muscle: H19, Myhas and Neat1 as potential biomarkers in amyotrophic lateral sclerosis.}, journal = {Open biology}, volume = {14}, number = {10}, pages = {240015}, pmid = {39406341}, issn = {2046-2441}, support = {//Gobierno de Aragón/ ; //Instituto de Salud Carlos III/ ; //European Union/ ; //Gobierno de España/ ; //Center for Biomedical Research/ ; }, mesh = {*RNA, Long Noncoding/genetics/metabolism ; Animals ; *Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology ; Mice ; *Muscle, Skeletal/metabolism/pathology ; *Mice, Transgenic ; *Disease Models, Animal ; *Biomarkers/metabolism ; Superoxide Dismutase-1/genetics/metabolism ; Humans ; Gene Expression Regulation ; Gene Expression Profiling ; Male ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a devastating neuromuscular disease characterized by progressive motor function and muscle mass loss. Despite extensive research in the field, the underlying causes of ALS remain incompletely understood, contributing to the absence of specific diagnostic and prognostic biomarkers and effective therapies. This study investigates the expression of long-non-coding RNAs (lncRNAs) in skeletal muscle as a potential source of biomarkers and therapeutic targets for the disease. The expression profiles of 12 lncRNAs, selected from the literature, were evaluated across different disease stages in tissue and muscle biopsies from the SOD1[G93A] transgenic mouse model of ALS. Nine out of the 12 lncRNAs were differentially expressed, with Pvt1, H19 and Neat1 showing notable increases in the symptomatic stages of the disease, and suggesting their potential as candidate biomarkers to support diagnosis and key players in muscle pathophysiology in ALS. Furthermore, the progression of Myhas and H19 RNA levels across disease stages correlated with longevity in the SOD1[G93A] animal model, effectively discriminating between long- and short-term survival individuals, thereby highlighting their potential as prognostic indicators. These findings underscore the involvement of lncRNAs, especially H19 and Myhas, in ALS pathophysiology, offering novel insights for diagnostic, prognostic and therapeutic targets.}, } @article {pmid39406000, year = {2024}, author = {Zhang, L and Du, Y and Deng, Y and Bai, T and Wang, J and Wang, W and Ji, M}, title = {Mutations in target gene confers resistance to acetolactate synthase inhibitors in Echinochloa phyllopogon.}, journal = {Plant physiology and biochemistry : PPB}, volume = {216}, number = {}, pages = {109194}, doi = {10.1016/j.plaphy.2024.109194}, pmid = {39406000}, issn = {1873-2690}, mesh = {*Acetolactate Synthase/genetics/antagonists & inhibitors/metabolism ; *Echinochloa/genetics/drug effects/enzymology ; *Herbicide Resistance/genetics ; *Herbicides/pharmacology ; *Mutation ; *Plant Proteins/genetics/metabolism ; Plants, Genetically Modified ; Enzyme Inhibitors/pharmacology ; Arabidopsis/genetics/enzymology/drug effects ; Molecular Docking Simulation ; Sulfonamides ; Uridine/analogs & derivatives ; }, abstract = {Echinochloa phyllopogon is a noxious weed that can harm rice over prolonged periods. Recently, a penoxsulam-resistant variant of E. phyllopogon with a mutation in the acetolactate synthase (ALS) gene was collected in Northeastern China. In the present study, the molecular mechanism underlying herbicide resistance in mutant populations was evaluated. The GR50 and IC50 values of the herbicide-resistant mutant 1-11 were 27.0- and 21.4-fold higher than those of the susceptible population 2-31, respectively. In addition, pre-application of malathion reduced the GR50 value of the resistant population. Additionally, mutant populations developed cross-resistance to other ALS inhibitors. E. phyllopogon ALS sequencing showed a Trp-574-Leu mutation in ALS2 variant 1-11. Molecular docking showed that the Trp-574-Leu substitution reduced the number of hydrogen bonds and altered the interaction between penoxsulam and ALS2. Transgenic Arabidopsis plants harboring the ALS2 mutant gene also showed resistance to penoxsulam and other ALS inhibitors. Overall, our study demonstrated that the Trp-574-Leu mutation and P450-mediated metabolic resistance lead to the cross-resistance of E. phyllopogon to ALS inhibitors.}, } @article {pmid39405005, year = {2024}, author = {Cheng, JL and Cook, AL and Talbot, J and Perry, S}, title = {How is Excitotoxicity Being Modelled in iPSC-Derived Neurons?.}, journal = {Neurotoxicity research}, volume = {42}, number = {5}, pages = {43}, pmid = {39405005}, issn = {1476-3524}, mesh = {*Induced Pluripotent Stem Cells/drug effects/physiology ; Humans ; *Neurons/drug effects/metabolism ; Animals ; *Amyotrophic Lateral Sclerosis/pathology/metabolism ; Cell Differentiation/drug effects/physiology ; }, abstract = {Excitotoxicity linked either to environmental causes (pesticide and cyanotoxin exposure), excitatory neurotransmitter imbalance, or to intrinsic neuronal hyperexcitability, is a pathological mechanism central to neurodegeneration in amyotrophic lateral sclerosis (ALS). Investigation of excitotoxic mechanisms using in vitro and in vivo animal models has been central to understanding ALS mechanisms of disease. In particular, advances in induced pluripotent stem cell (iPSC) technologies now provide human cell-based models that are readily amenable to environmental and network-based excitotoxic manipulations. The cell-type specific differentiation of iPSC, combined with approaches to modelling excitotoxicity that include editing of disease-associated gene variants, chemogenetics, and environmental risk-associated exposures make iPSC primed to examine gene-environment interactions and disease-associated excitotoxic mechanisms. Critical to this is knowledge of which neurotransmitter receptor subunits are expressed by iPSC-derived neuronal cultures being studied, how their activity responds to antagonists and agonists of these receptors, and how to interpret data derived from multi-parameter electrophysiological recordings. This review explores how iPSC-based studies have contributed to our understanding of ALS-linked excitotoxicity and highlights novel approaches to inducing excitotoxicity in iPSC-derived neurons to further our understanding of its pathological pathways.}, } @article {pmid39404920, year = {2025}, author = {Aiello, EN and Curti, B and Torre, S and De Luca, G and Maranzano, A and Colombo, E and Gendarini, C and Cocuzza, A and Messina, S and Doretti, A and Verde, F and Morelli, C and Silani, V and Ticozzi, N and Poletti, B}, title = {Clinical usefulness of the Verbal Fluency Index (VFI) in amyotrophic lateral sclerosis.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {46}, number = {2}, pages = {775-782}, pmid = {39404920}, issn = {1590-3478}, support = {NA//Ministero della Salute/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/complications/diagnosis/psychology/physiopathology ; Male ; Female ; Middle Aged ; Aged ; *Neuropsychological Tests ; *Verbal Behavior/physiology ; Executive Function/physiology ; Severity of Illness Index ; Italy ; }, abstract = {BACKGROUND: This study aimed at assessing the clinical utility of the Verbal Fluency Index (VFI) over a classical phonemic verbal fluency test in Italian-speaking amyotrophic lateral sclerosis (ALS) patients.

METHODS: N = 343 non-demented ALS patients and N = 226 healthy controls (HCs) were administered the Verbal fluency - S task from the Edinburgh Cognitive and Behavioural ALS Screen (ECAS). The associations between the number of words produced (NoW), the time to read words aloud (TRW) and the VFI (computed as [(60"-TRW)/NoW]) on one hand and both bulbar/respiratory scores from the ALS Functional Rating Scale - Revised (ALSFRS-R) and the ECAS-Executive on the other were tested. Italian norms for the NoW and the VFI were derived in HCs via the Equivalent Score method. Patients were classified based on their impaired/unimpaired performances on the NoW and the VFI (NoW-VFI-; NoW-VFI+; NoW + VFI-; NoW + VFI+), with these groups being compared on ECAS-Executive scores.

RESULTS: The VFI, but neither the NoW nor the TRW, were related to ALSFRS-Bulbar/-Respiratory scores; VFI and NoW measures, but not the TRW, were related to the ECAS-Executive (p < .001). The NoW slightly overestimated the number of executively impaired patients when compared to the VFI (31.1% vs. 26.8%, respectively). Patients with a defective VFI score - regardless of whether they presented or not with a below-cutoff NoW - reported worse ECAS-Executive scores than NoW + VFI + ones.

CONCLUSIONS: The present reports support the use of the Italian VFI as a mean to validly assess ALS patients' executive status by limiting the effect of motor disabilities that might undermine their speech rate.}, } @article {pmid39404532, year = {2024}, author = {Tanioka, S and Wu, B and Ballmer, SW}, title = {Experimental demonstration of frequency- downconverted arm-length stabilization for a future upgraded gravitational wave detector.}, journal = {Optics letters}, volume = {49}, number = {20}, pages = {5763-5766}, doi = {10.1364/OL.534141}, pmid = {39404532}, issn = {1539-4794}, abstract = {Ground-based laser interferometric gravitational wave detectors (GWDs) consist of multiple optical cavity systems whose lengths need to be interferometrically controlled. An arm-length stabilization (ALS) system has played an important role in bringing these interferometers into an operational state and enhancing their duty cycle. The sensitivity of these detectors can be improved if the thermal noise of their test mass mirror coatings is reduced. Crystalline AlGaAs coatings are a promising candidate for this. However, the current ALS system with a frequency-doubled 532 nm light is no longer an option with AlGaAs coatings because the 532 nm light is absorbed by AlGaAs coatings due to the narrow bandgap of GaAs. Therefore, alternative locking schemes must be developed. In this Letter, we describe an experimental demonstration of a novel ALS scheme, to the best of our knowledge, which is compatible with AlGaAs coatings. This ALS scheme will enable the use of AlGaAs coatings in current and future terrestrial gravitational wave detectors.}, } @article {pmid39403566, year = {2024}, author = {Biswas, DD and Sethi, R and Woldeyohannes, Y and Scarrow, ER and El Haddad, L and Lee, J and ElMallah, MK}, title = {Respiratory pathology in the TDP-43 transgenic mouse model of amyotrophic lateral sclerosis.}, journal = {Frontiers in physiology}, volume = {15}, number = {}, pages = {1430875}, pmid = {39403566}, issn = {1664-042X}, support = {R21 NS098131/NS/NINDS NIH HHS/United States ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease that results in death within 2-5 years of diagnosis. Respiratory failure is the most common cause of death in ALS. Mutations in the transactive response DNA binding protein 43 (TDP-43) encoded by the TARDBP gene are associated with abnormal cellular aggregates in neurons of patients with both familial and sporadic ALS. The role of these abnormal aggregates on breathing is unclear. Since respiratory failure is a major cause of death in ALS, we sought to determine the role of TDP-43 mutations on the respiratory motor unit in the Prp-hTDP-43[A315T] mouse model - a model that expresses human TDP-43 containing the A315T mutation. We assessed breathing using whole-body plethysmography, and investigated neuropathology in hypoglossal and phrenic respiratory motor units. Postmortem studies included quantification of hypoglossal and putative phrenic motor neurons, activated microglia and astrocytes in respiratory control centers, and assessment of hypoglossal and phrenic nerves of TDP43[A315T] mice. The male TDP43[A315T] mice display an early onset of rapid progression of disease, and premature death (less than 15 weeks) compared to control mice and compared to female TDP43[A315T] mice who die between 20 and 35 weeks of age. The TDP43[A315T] mice have progressive and profound breathing deficits at baseline and during a respiratory challenge. Histologically, hypoglossal and putative phrenic motor neurons of TDP43[A315T] mice are decreased and have increased microglial and astrocyte activation, indicating pronounced neurodegeneration and neuroinflammation. Further, there is axonopathy and demyelination in the hypoglossal and phrenic nerve of TDP43[A315T] mice. Thus, the TDP-43[A315T] mice have significant respiratory pathology and neuropathology, which makes them a useful translatable model for the study of novel therapies on breathing in ALS.}, } @article {pmid39403300, year = {2024}, author = {Aminianfar, A and Fatemi, MH and Azimi, F}, title = {Comprehensive characterization of volatile compounds in Iranian black teas using chemometric analysis of GC-MS fingerprints.}, journal = {Food chemistry: X}, volume = {24}, number = {}, pages = {101859}, pmid = {39403300}, issn = {2590-1575}, abstract = {Black tea, a widely popular non-alcoholic beverage, is renowned for its unique aroma and has attracted significant attention due to its complex composition. However, the chemical profile of Iranian tea remains largely unexplored. In this research, black tea samples from key tea cultivation regions in four geographical areas in northern Iran were firstly analyzed using headspace solid-phase microextraction followed by gas chromatography-mass spectrometry (HS-SPME-GC-MS) to separate, identify, and quantify their volatile organic compounds. Subsequently, employing a robust investigative strategy, we utilized for the first time the well-known multivariate curve resolution-alternating least square (MCR-ALS) method as a deconvolution technique to analyze the complex GC-MS peak clusters of tea samples. This approach effectively addressed challenges such as severe baseline drifts, overlapping peaks, and background noise, enabling the identification of minor components responsible for the distinct flavors and tastes across various samples. The MCR-ALS technique significantly improved the resolution of spectral and elution profiles, enabling both qualitative and semi-quantitative analysis of tea constituents. Qualitative analysis involved comparing resolved peak profiles to theoretical spectra, along with retention indices, while semi-quantification was conducted using the overall volume integration (OVI) approach for volatile compounds, providing a more accurate correlation between peak areas and concentrations. The application of chemometric tools in GC-MS analysis increased the number of recognized components in four tea samples, expanding from 54 to 256 components, all with concentrations exceeding 0.1 %. Among them, 32 volatile compounds were present in every tea sample. Hydrocarbons (including alkenes, alkanes, cycloalkanes, monoterpenes and sesquiterpenes), esters and alcohols were the three major chemical classes, comprising 78 % of the total relative content of volatile compounds. Analyzing black teas from four distinct regions revealed variations not only in their volatile components but also in their relative proportions. This integrated approach provides a comprehensive understanding of the volatile chemical profiles in Iranian black teas, enhances knowledge about their unique characteristics across diverse geographical origin, and lays the groundwork for quality improvement.}, } @article {pmid39402245, year = {2024}, author = {Wood, H}, title = {Altered muscle cholesterol transport in ALS.}, journal = {Nature reviews. Neurology}, volume = {20}, number = {11}, pages = {643}, doi = {10.1038/s41582-024-01029-8}, pmid = {39402245}, issn = {1759-4766}, } @article {pmid39402174, year = {2025}, author = {Jellinger, KA}, title = {The spectrum of behavioral disorders in amyotrophic lateral sclerosis: current view.}, journal = {Journal of neural transmission (Vienna, Austria : 1996)}, volume = {132}, number = {2}, pages = {217-236}, pmid = {39402174}, issn = {1435-1463}, support = {Society for the Promotion of Research in Experimental Neurology, Vienna, Austria//Society for the Promotion of Research in Experimental Neurology, Vienna, Austria/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/complications/physiopathology/pathology/psychology ; *Mental Disorders/etiology/physiopathology ; *Brain/physiopathology/pathology ; }, abstract = {Behavioral disorders, with an average prevalence of 30-60% are important non-motor symptoms in amyotrophic lateral sclerosis (ALS) that have a negative impact on prognosis, management and quality of life, yet the underlying neurobiology is poorly understood. Among people with ALS, apathy, fatigue, anxiety, irritability and other behavioral symptoms are the most prominent, although less frequent than cognitive impairment. The present review explores the current understanding of behavioral changes in ALS with particular emphasis on our current knowledge about their structural and functional brain correlates, substantiating a multisystem degeneration with particular dysfunction of frontal-subcortical circuits and dysfunction of fronto-striatal, frontotemporal and other essential brain systems. The natural history of behavioral dysfunctions in ALS and their relationship to frontotemporal lobe degeneration (FTLD) are not fully understood, although they form a clinical continuum, suggesting a differential vulnerability of non-motor brain networks, ALS being considered a brain network disorder. An assessment of risks or the early detection of brain connectivity signatures before structural changes may be helpful in investigating the pathophysiological mechanisms of behavioral impairment in ALS. Treatment of both ALS and co-morbid behavioral disorders is a multidisciplinary task, but whereas no causal or disease-modifying therapies for ALS are available, symptomatic treatment of a variety of behavioral symptoms plays a pivotal role in patient care, although the management of behavioral symptoms in clinical care still remains limited.}, } @article {pmid39401554, year = {2025}, author = {Duarte, RRR and Nixon, DF and Powell, TR}, title = {Ancient viral DNA in the human genome linked to neurodegenerative diseases.}, journal = {Brain, behavior, and immunity}, volume = {123}, number = {}, pages = {765-770}, pmid = {39401554}, issn = {1090-2139}, mesh = {Humans ; *Neurodegenerative Diseases/genetics/virology ; *Endogenous Retroviruses/genetics ; *Genome, Human ; Genome-Wide Association Study ; DNA, Viral/genetics ; Amyotrophic Lateral Sclerosis/genetics/virology ; Multiple Sclerosis/genetics/virology ; Genetic Predisposition to Disease/genetics ; Brain/metabolism/virology ; Parkinson Disease/genetics/virology ; Male ; Female ; }, abstract = {BACKGROUND: Human endogenous retroviruses (HERVs) are sequences in the human genome that originated from infections with ancient retroviruses during our evolution. Previous studies have linked HERVs to neurodegenerative diseases, but defining their role in aetiology has been challenging. Here, we used a retrotranscriptome-wide association study (rTWAS) approach to assess the relationships between genetic risk for neurodegenerative diseases and HERV expression in the brain, calculated with genomic precision.

METHODS: We analysed genetic association statistics pertaining to Alzheimer's disease, amyotrophic lateral sclerosis, multiple sclerosis, and Parkinson's disease, using HERV expression models calculated from 792 cortical samples. Robust risk factors were considered those that survived multiple testing correction in the primary analysis, which were also significant in conditional and joint analyses, and that had a posterior inclusion probability above 0.5 in fine-mapping analyses.

RESULTS: The primary analysis identified 12 HERV expression signatures associated with neurodegenerative disease susceptibility. We found one HERV expression signature robustly associated with amyotrophic lateral sclerosis on chromosome 12q14 (MER61_12q14.2) and one robustly associated with multiple sclerosis on chromosome 1p36 (ERVLE_1p36.32a). A co-expression analysis suggested that these HERVs are involved in homophilic cell adhesion via plasma membrane adhesion molecules.

CONCLUSIONS: We found HERV expression profiles robustly associated with amyotrophic lateral sclerosis and multiple sclerosis susceptibility, highlighting novel risk mechanisms underlying neurodegenerative disease, and offering potential new targets for therapeutic intervention.}, } @article {pmid39401249, year = {2024}, author = {Pérez de la Lastra Aranda, C and Tosat-Bitrián, C and Porras, G and Dafinca, R and Muñoz-Torrero, D and Talbot, K and Martín-Requero, Á and Martínez, A and Palomo, V}, title = {Proteome Aggregation in Cells Derived from Amyotrophic Lateral Sclerosis Patients for Personalized Drug Evaluation.}, journal = {ACS chemical neuroscience}, volume = {15}, number = {21}, pages = {3945-3953}, doi = {10.1021/acschemneuro.4c00328}, pmid = {39401249}, issn = {1948-7193}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism/genetics/drug therapy/pathology ; *Proteome/metabolism ; Precision Medicine/methods ; Motor Neurons/metabolism/drug effects ; Lymphocytes/metabolism/drug effects ; Protein Aggregates/drug effects/physiology ; Induced Pluripotent Stem Cells/metabolism/drug effects ; Protein Aggregation, Pathological/metabolism ; DNA-Binding Proteins/metabolism ; Drug Evaluation, Preclinical/methods ; Mutation ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder that currently lacks effective therapy. Given the heterogeneity of clinical and molecular profiles of ALS patients, personalized diagnostics and pathological characterization represent a powerful strategy to optimize patient stratification, thereby enabling personalized treatment. Immortalized lymphocytes from sporadic and genetic ALS patients recapitulate some pathological hallmarks of the disease, facilitating the fundamental task of drug screening. However, the molecular aggregation of ALS has not been characterized in this patient-derived cellular model. Indeed, protein aggregation is one of the most prominent features of neurodegenerative diseases, and therefore, models to test drugs against personalized pathological aggregation could help discover improved therapies. With this work, we aimed to characterize the aggregation profile of ALS immortalized lymphocytes and test several drug candidates with different mechanisms of action. In addition, we have evaluated the molecular aggregation in motor neurons derived from two hiPSC cell lines corresponding to ALS patients with different mutations in TARDBP. The results provide valuable insight into the different characterization of sporadic and genetic ALS patients' immortalized lymphocytes, their differential response to drug treatment, and the usefulness of proteome homeostasis characterization in patients' cells.}, } @article {pmid39400557, year = {2024}, author = {Gelpi, E and Reinecke, R and Gaig, C and Iranzo, A and Sabater, L and Molina-Porcel, L and Aldecoa, I and Endmayr, V and Högl, B and Schmutzhard, E and Poewe, W and Pfausler, B and Popovic, M and Pretnar-Oblak, J and Leypoldt, F and Matschke, J and Glatzel, M and Erro, EM and Jerico, I and Caballero, MC and Zelaya, MV and Mariotto, S and Heidbreder, A and Kalev, O and Weis, S and Macher, S and Berger-Sieczkowski, E and Ferrari, J and Reisinger, C and Klupp, N and Tienari, P and Rautila, O and Niemelä, M and Yilmazer-Hanke, D and Guasp, M and Bloem, B and Van Gaalen, J and Kusters, B and Titulaer, M and Fransen, NL and Santamaria, J and Dawson, T and Holton, JL and Ling, H and Revesz, T and Myllykangas, L and Budka, H and Kovacs, GG and Lewerenz, J and Dalmau, J and Graus, F and Koneczny, I and Höftberger, R}, title = {Neuropathological spectrum of anti-IgLON5 disease and stages of brainstem tau pathology: updated neuropathological research criteria of the disease-related tauopathy.}, journal = {Acta neuropathologica}, volume = {148}, number = {1}, pages = {53}, pmid = {39400557}, issn = {1432-0533}, support = {SYNABS//Austrian Science Fund/ ; I6565-B//Austrian Science Fund/ ; T996-B30//Austrian Science Fund/ ; 01GM2208B//Bundesministerium für Bildung und Forschung/ ; 01GM2208A//Bundesministerium für Bildung und Forschung/ ; PI21/00165//Instituto de Salud Carlos III/ ; PI21/00165//Instituto de Salud Carlos III/ ; N° 825575//Horizon 2020 Framework Programme/ ; 341007//Tekniikan Akatemia/ ; TYH2022316//Helsingin Yliopisto/ ; }, mesh = {Humans ; *Tauopathies/pathology/immunology ; Middle Aged ; *Brain Stem/pathology/metabolism/immunology ; Male ; Female ; Aged ; Aged, 80 and over ; *tau Proteins/metabolism/immunology ; *Cell Adhesion Molecules, Neuronal/metabolism/immunology ; Adult ; Autoantibodies/immunology ; DNA-Binding Proteins/metabolism ; }, abstract = {Anti-IgLON5 disease is a unique condition that bridges autoimmunity and neurodegeneration. Since its initial description 10 years ago, an increasing number of autopsies has led to the observation of a broader spectrum of neuropathologies underlying a particular constellation of clinical symptoms. In this study, we describe the neuropathological findings in 22 patients with anti-IgLON5 disease from 9 different European centers. In 15 patients (68%), we observed a hypothalamic and brainstem-predominant tauopathy of varying severity in which the original research neuropathological criteria were readily applicable. This pathology was observed in younger patients (median age at onset 61 years) with a long disease duration (median 9 years). In contrast, in 7 (32%) patients, the originally described brainstem tauopathy was nearly absent or only minimal in the form of delicate threads, despite mild-to-moderate neurodegenerative features, consistent clinical symptoms and the presence of anti-IgLON5 antibodies in CSF and serum. These patients were older at onset (median 79 years) and had shorter disease duration (median < 1 year). Overall, about one-third of the patients showed concomitant TDP-43 pathology within the regions affected by tau pathology and/or neurodegeneration. Based on these observations and in view of the spectrum of the tau burden in the core regions involved in the disease, we propose a simple staging system: stage 1 mild neurodegeneration without overt or only minimal tau pathology, stage 2 moderate neurodegeneration and mild/ moderate tauopathy and stage 3 prominent neurodegeneration and tau pathology. This staging intends to reflect a potential (age- and time-dependent) progression of tau pathology, supporting the current notion that tau accumulation is a secondary phenomenon related to the presence of anti-IgLON5 antibodies in the CNS. Finally, we adapt the original research criteria of the anti-IgLON5 disease-related tauopathy to include the spectrum of pathologies observed in this larger postmortem series.}, } @article {pmid39400020, year = {2024}, author = {Ali, A and A Emad, N and Sultana, N and Waheed, A and Aqil, M and Sultana, Y and Mujeeb, M}, title = {Navigating into the Paradigm of Nose-to-brain Delivery of Nanotherapeutics and their Repurposing as Nanotheranostics for Neurodegenerative Diseases.}, journal = {CNS & neurological disorders drug targets}, volume = {}, number = {}, pages = {}, doi = {10.2174/0118715273319597240927044906}, pmid = {39400020}, issn = {1996-3181}, abstract = {Repurposing drugs for neurodegenerative diseases using the nose-to-brain route of administration is an intriguing concept with potential benefits. The nose-to-brain route involves delivering drugs directly to the brain via the olfactory or trigeminal pathways, bypassing the blood-brain barrier, which can improve drug efficacy and reduce systemic side effects. Treatment of numerous neurodegenerative diseases such as Multiple sclerosis, Amyotrophic lateral sclerosis, Huntington's, Alzheimer's, and Parkinson's diseases has been attempted using this route of administration. These drugs may include neuroprotective agents, anti-inflammatory drugs, antioxidants, or diseasemodifying therapies. Nanotheranostics, which integrates therapeutic and diagnostic functions in a nanosystem, improves treatment precision and efficacy. Repurposing nanotherapeutics as nanotheranostics for neurodegenerative diseases through the nose-to-brain route of administration holds great potential for both diagnosis and treatment. This review highlights the various mechanisms engaged in transporting nanocarriers from nose-to-brain and the proposed fate of these nanocarriers using different live imaging techniques. Additionally, the discussion covers the recent combinatorial therapeutic approaches and theranostic applications of various nanocarriers used for neurodegenerative diseases through the nose-to-brain. Toxicity to the CNS and nasal mucosa and regulatory considerations about these delivery systems are also deliberated. Overall, repurposed nanoparticles designed as nanotheranostic agents offer a versatile platform for precise diagnosis, targeted therapy, and personalized management of neurodegenerative diseases, holding great promise for improving patient care and advancing our understanding of these complex disorders.}, } @article {pmid39399380, year = {2024}, author = {Cossu, L and Cappon, G and Facchinetti, A}, title = {Automated pipeline for denoising, missing data processing, and feature extraction for signals acquired via wearable devices in multiple sclerosis and amyotrophic lateral sclerosis applications.}, journal = {Frontiers in digital health}, volume = {6}, number = {}, pages = {1402943}, pmid = {39399380}, issn = {2673-253X}, abstract = {INTRODUCTION: The incorporation of health-related sensors in wearable devices has increased their use as essential monitoring tools for a wide range of clinical applications. However, the signals obtained from these devices often present challenges such as artifacts, spikes, high-frequency noise, and data gaps, which impede their direct exploitation. Additionally, clinically relevant features are not always readily available. This problem is particularly critical within the H2020 BRAINTEASER project, funded by the European Community, which aims at developing models for the progression of Multiple Sclerosis (MS) and Amyotrophic Lateral Sclerosis (ALS) using data from wearable devices.

METHODS: The objective of this study is to present the automated pipeline developed to process signals and extract features from the Garmin Vivoactive 4 smartwatch, which has been chosen as the primary wearable device in the BRAINTEASER project. The proposed pipeline includes a signal processing step, which applies retiming, gap-filling, and denoising algorithms to enhance the quality of the data. The feature extraction step, on the other hand, utilizes clinical partners' knowledge and feedback to select the most relevant variables for analysis.

RESULTS: The performance and effectiveness of the proposed automated pipeline have been evaluated through pivotal beta testing sessions, which demonstrated the ability of the pipeline to improve the data quality and extract features from the data. Further clinical validation of the extracted features will be performed in the upcoming steps of the BRAINTEASER project.

DISCUSSION: Developed in Python, this pipeline can be used by researchers for automated signal processing and feature extraction from wearable devices. It can also be easily adapted or modified to suit the specific requirements of different scenarios.}, } @article {pmid39397192, year = {2024}, author = {Hamdi, N and Mueller, K and Hamza, A and Soliman, R and Onbool, E and Omran, K and Ocab, O and Freischmidt, A and Siebert, R and Ludolph, A and Fahmy, N}, title = {First insights into genotype and phenotype of familial amyotrophic lateral sclerosis in Egypt: early onset and high consanguinity.}, journal = {Frontiers of medicine}, volume = {18}, number = {6}, pages = {1115-1118}, pmid = {39397192}, issn = {2095-0225}, } @article {pmid39396990, year = {2024}, author = {Hazell, G and McCallion, E and Ahlskog, N and Sutton, ER and Okoh, M and Shaqoura, EIH and Hoolachan, JM and Scaife, T and Iqbal, S and Bhomra, A and Kordala, AJ and Scamps, F and Raoul, C and Wood, MJA and Bowerman, M}, title = {Exercise, disease state and sex influence the beneficial effects of Fn14-depletion on survival and muscle pathology in the SOD1[G93A] amyotrophic lateral sclerosis (ALS) mouse model.}, journal = {Skeletal muscle}, volume = {14}, number = {1}, pages = {23}, pmid = {39396990}, issn = {2044-5040}, support = {SBF006/1162/AMS_/Academy of Medical Sciences/United Kingdom ; SBF006/1162/AMS_/Academy of Medical Sciences/United Kingdom ; MR/Y003640/1/MRC_/Medical Research Council/United Kingdom ; MR/Y003640/1/MRC_/Medical Research Council/United Kingdom ; 18GRO-PS48-0114//Muscular Dystrophy UK/ ; 18GRO-PS48-0114//Muscular Dystrophy UK/ ; }, mesh = {Animals ; *Amyotrophic Lateral Sclerosis/metabolism/genetics/pathology ; *TWEAK Receptor/metabolism/genetics ; *Muscle, Skeletal/metabolism/pathology ; Male ; Female ; *Disease Models, Animal ; *Mice, Transgenic ; Mice ; Physical Conditioning, Animal ; Mice, Knockout ; Cytokine TWEAK/metabolism/genetics ; Superoxide Dismutase-1/genetics/metabolism ; Mice, Inbred C57BL ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a devastating and incurable neurodegenerative disease. Accumulating evidence strongly suggests that intrinsic muscle defects exist and contribute to disease progression, including imbalances in whole-body metabolic homeostasis. We have previously reported that tumour necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) and fibroblast growth factor inducible 14 (Fn14) are significantly upregulated in skeletal muscle of the SOD1[G93A] ALS mouse model. While antagonising TWEAK did not impact survival, we did observe positive effects in skeletal muscle. Given that Fn14 has been proposed as the main effector of the TWEAK/Fn14 activity and that Fn14 can act independently from TWEAK in muscle, we suggest that manipulating Fn14 instead of TWEAK in the SOD1[G93A] ALS mice could lead to differential and potentially improved benefits.

METHODS: We thus investigated the contribution of Fn14 to disease phenotypes in the SOD1[G93A] ALS mice. To do so, Fn14 knockout mice (Fn14[-/-]) were crossed onto the SOD1[G93A] background to generate SOD1[G93A];Fn14[-/-] mice. Investigations were performed on both unexercised and exercised (rotarod and/or grid test) animals (wild type (WT), Fn14[-/-], SOD1[G93A] and SOD1[G93A];Fn14[-/-]).

RESULTS: Here, we firstly confirm that the TWEAK/Fn14 pathway is dysregulated in skeletal muscle of SOD1[G93A] mice. We then show that Fn14-depleted SOD1[G93A] mice display increased lifespan, myofiber size, neuromuscular junction endplate area as well as altered expression of known molecular effectors of the TWEAK/Fn14 pathway, without an impact on motor function. Importantly, we also observe a complex interaction between exercise (rotarod and grid test), genotype, disease state and sex that influences the overall effects of Fn14 deletion on survival, expression of known molecular effectors of the TWEAK/Fn14 pathway, expression of myosin heavy chain isoforms and myofiber size.

CONCLUSIONS: Our study provides further insights on the different roles of the TWEAK/Fn14 pathway in pathological skeletal muscle and how they can be influenced by age, disease, sex and exercise. This is particularly relevant in the ALS field, where combinatorial therapies that include exercise regimens are currently being explored. As such, a better understanding and consideration of the interactions between treatments, muscle metabolism, sex and exercise will be of importance in future studies.}, } @article {pmid39396709, year = {2024}, author = {Wu, J and Wu, J and Chen, T and Cai, J and Ren, R}, title = {Protein aggregation and its affecting mechanisms in neurodegenerative diseases.}, journal = {Neurochemistry international}, volume = {180}, number = {}, pages = {105880}, doi = {10.1016/j.neuint.2024.105880}, pmid = {39396709}, issn = {1872-9754}, mesh = {Humans ; *Neurodegenerative Diseases/metabolism/pathology ; Animals ; Protein Aggregation, Pathological/metabolism ; alpha-Synuclein/metabolism ; Amyloid beta-Peptides/metabolism ; Protein Aggregates/physiology ; tau Proteins/metabolism ; }, abstract = {Protein aggregation serves as a critical pathological marker in a spectrum of neurodegenerative diseases (NDs), including the formation of amyloid β (Aβ) and Tau neurofibrillary tangles in Alzheimer's disease, as well as α-Synuclein (α-Syn) aggregates in Parkinson's disease, Parkinson's disease-related dementia (PDD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). A significant proportion of patients with amyotrophic lateral sclerosis (ALS) exhibit TDP-43 aggregates. Moreover, a confluence of brain protein pathologies, such as Aβ, Tau, α-Syn, and TDP-43, has been identified in individual NDs cases, highlighting the intricate interplay among these proteins that is garnering heightened scrutiny. Importantly, protein aggregation is modulated by an array of factors, with burgeoning evidence suggesting that it frequently results from perturbations in protein homeostasis, influenced by the cellular membrane milieu, metal ion concentrations, post-translational modifications, and genetic mutations. This review delves into the pathological underpinnings of protein aggregation across various NDs and elucidates the intercommunication among disparate proteins within the same disease context. Additionally, we examine the pathogenic mechanisms by which diverse factors impinge upon protein aggregation, offering fresh perspectives for the future therapeutic intervention of NDs.}, } @article {pmid39396264, year = {2024}, author = {Bermudo Fuenmayor, S and Serrano Castro, PJ and Quiroga Subirana, P and López Palmero, S and Requena Mullor, MM and Parrón Carreño, T}, title = {Design and validation of a questionnaire for monitoring neurological dysphagia and respiratory deterioration in patients with amyotrophic lateral sclerosis (DEREDELA).}, journal = {Neurologia}, volume = {39}, number = {8}, pages = {666-674}, doi = {10.1016/j.nrleng.2024.09.003}, pmid = {39396264}, issn = {2173-5808}, mesh = {*Amyotrophic Lateral Sclerosis/complications ; Humans ; *Deglutition Disorders/diagnosis/etiology ; Surveys and Questionnaires ; Male ; Female ; Reproducibility of Results ; Middle Aged ; Aged ; }, abstract = {INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a degenerative disease of unknown origin that affects the motor neurons. It has a rapid, fatal course.

METHOD: For this study, an initial questionnaire of eleven items was developed by experts in the field, who evaluated the suitability and relevance of the items.

RESULTS: The questionnaire was then applied to a pilot group of 22 patients diagnosed with ALS. Confirmatory factor analysis, based on estimating maximum likelihood, confirmed the three domains detected in the exploratory factor analysis. The reliability of the scale was tested using Cronbach's α (0.801) and the Kaiser-Meyer-Olkin test (0.770) confirmed the construct validity.

CONCLUSIONS: The DEREDELA questionnaire is valid, in terms of its content, for monitoring the neurological dysphagia and respiratory deterioration suffered by patients diagnosed with ALS.}, } @article {pmid39395841, year = {2024}, author = {Tran, M and Rhee, J and Hu, W and Magin, P and Shulruf, B}, title = {General practice trainee, supervisor and educator perspectives on the transitions in postgraduate training: a scoping review.}, journal = {Family medicine and community health}, volume = {12}, number = {4}, pages = {}, pmid = {39395841}, issn = {2009-8774}, mesh = {Humans ; *General Practice/education ; Education, Medical, Graduate ; General Practitioners/education ; Students, Medical/psychology ; }, abstract = {UNLABELLED: Transitions are a period and a process, through which there is a longitudinal adaptation in response to changing circumstances in clinical practice and responsibilities. While the experience of the transition in medical student learning and in hospital-based specialty training programmes are well described and researched, the experience of the transition in community-based postgraduate general practitioner (GP) training has not been described comprehensively.

OBJECTIVE: We aimed to identify, and categorise, the formative experiences of transitions in GP training and their impacts on personal and professional development.

DESIGN: We adopted Levac et al's scoping review methodology. Of 1543 retrieved records, 76 were selected for data extraction. Based on a combined model of the socioecological and multiple and multi-dimensional theories of transitions, data relating to the experiences of transitions were organised into contextual themes: being physical, psychosocial, organisational culture and chronological.

ELIGIBILITY CRITERIA: Empirical studies focused on general practice trainees or training, that discussed the transitions experienced in general practice training and that were published in English were included.

INFORMATION SOURCES: PubMed, MEDLINE and Web of Science databases were searched in January 2024 with no date limits for empirical studies on the transition experiences of GP into, and through, training.

RESULTS: Our findings describe context-dependent formative experiences which advance, or impede, learning and development. Time is a significant modulator of the factors contributing to more negative experiences, with some initially adverse experiences becoming more positive. Identification of the inflection point that represents a shift from initially adverse to more positive experiences of transitions may help moderate expectations for learning and performance at different stages of training.

CONCLUSION: Challenges in training can either advance development and contribute positively to professional identity formation and clinical competency, or detract from learning and potentially contribute to burnout and attrition from training programmes. These findings will assist future research in identifying predictive factors of positive and adverse experiences of transitions and may strengthen existing and nascent GP training programmes. The findings are transferable to other community-based specialty training programmes.}, } @article {pmid39395630, year = {2024}, author = {Yeewa, R and Sangphukieo, A and Jantaree, P and Wongkummool, W and Yamsri, T and Poompouang, S and Chaiyawat, P and Lo Piccolo, L and Jantrapirom, S}, title = {ERO1A inhibition mitigates neuronal ER stress and ameliorates UBQLN2[ALS] phenotypes in Drosophila melanogaster.}, journal = {Progress in neurobiology}, volume = {242}, number = {}, pages = {102674}, doi = {10.1016/j.pneurobio.2024.102674}, pmid = {39395630}, issn = {1873-5118}, mesh = {Animals ; *Drosophila melanogaster ; *Endoplasmic Reticulum Stress/drug effects/physiology ; *Drosophila Proteins/metabolism/genetics ; *Neurons/metabolism/drug effects ; Phenotype ; Autophagy-Related Proteins/metabolism/genetics ; Disease Models, Animal ; Animals, Genetically Modified ; Neurodegenerative Diseases/drug therapy/metabolism ; }, abstract = {Modulating the ER stress pathway holds therapeutic promise for neurodegenerative diseases; however, identifying optimal targets remains challenging. In this study, we conducted an unbiased screening to systematically search for commonly up-regulated proteins in ER stress-related neurodegenerative conditions, with endoplasmic reticulum oxidoreductase 1 alpha (ERO1A) emerging as a significant hit. Further experiments conducted in the model organism Drosophila melanogaster demonstrated that elevated levels of Drosophila ERO1A (ERO1L) were indeed detrimental to neurons. Conversely, genetic suppression or pharmacological inhibition of ERO1L activity provided neuroprotection under ER stress and extended the lifespan of flies. To translate these findings, we performed a genetic modifier screening and underscored significant neuroprotective effects against UBQLN2[ALS] pathology. Additionally, administration of the chemical probe inhibitor of ERO1A, known as EN460, enhanced locomotive functions and neuromuscular junction (NMJ) morphology in Drosophila UBQLN2[ALS] model. Mechanistically, targeting ERO1L during environmental or pathological ER stress mitigated proteotoxic stress by lowering either the PERK or IRE1 branches of the unfolded protein response (UPR). These findings suggest ERO1A as a promising therapeutic target in UBQLN2[ALS] and other ER stress-related conditions.}, } @article {pmid39395475, year = {2024}, author = {Kim, SY and Kim, M and Park, K and Hong, S}, title = {A systematic review on analytical methods of the neurotoxin β-N-methylamino-L-alanine (BMAA), and its causative microalgae and distribution in the environment.}, journal = {Chemosphere}, volume = {366}, number = {}, pages = {143487}, doi = {10.1016/j.chemosphere.2024.143487}, pmid = {39395475}, issn = {1879-1298}, mesh = {*Amino Acids, Diamino/analysis ; *Microalgae/metabolism ; *Cyanobacteria Toxins ; *Neurotoxins/analysis ; *Cyanobacteria/metabolism ; *Tandem Mass Spectrometry ; *Environmental Monitoring/methods ; Ecosystem ; Chromatography, Liquid ; Diatoms/metabolism ; Water Pollutants, Chemical/analysis/metabolism ; }, abstract = {β-N-Methylamino-L-alanine (BMAA), a neurotoxin produced by various microalgal groups, is associated with neurodegenerative diseases and is considered a major environmental factor potentially linked to sporadic amyotrophic lateral sclerosis. This study systematically reviews the analytical methods used to study BMAA in publications from 2019 to the present. It also investigates the causative microalgae of BMAA and its geographical distributions in aquatic ecosystems based on studies conducted since 2003. A comprehensive search using the Web of Science database revealed that hydrolysis for extraction (67%), followed by quantification using LC-MS/MS (LC: 84%; MS/MS: 88%), is the most commonly employed method in BMAA analysis. Among analytical methods, RPLC-MS/MS had the highest percentage (88%) of BMAA-positive results and included a high number of quality control (QC) assessments. Various genera of cyanobacteria and diatoms have been reported to produce BMAA. The widespread geographical distribution of BMAA across diverse ecosystems highlights significant environmental and public health concerns. Notably, BMAA accumulation and biomagnification are likely more potent in marine or brackish water ecosystems than in freshwater ecosystems, potentially amplifying its ecological impacts. Future research should prioritize advanced, sensitive methods, particularly LC-MS/MS with as many QC assessments as possible, and should expand investigations to identify novel microalgal producers and previously uncharted geographical areas, with a special focus on marine or brackish water ecosystems. This effort will enhance our understanding of the environmental distribution and impacts of BMAA.}, } @article {pmid39394860, year = {2024}, author = {Zhao, J and Kong, D and Zhang, G and Zhang, S and Wu, Y and Dai, C and Chen, Y and Yang, Y and Liu, Y and Wei, D}, title = {An Efficient CRISPR/Cas Cooperative Shearing Platform for Clinical Diagnostics Applications.}, journal = {Angewandte Chemie (International ed. in English)}, volume = {63}, number = {52}, pages = {e202411705}, doi = {10.1002/anie.202411705}, pmid = {39394860}, issn = {1521-3773}, support = {22304031, 61890940//National Natural Science Foundation of China/ ; 2021YFC2301100//the National Key R&D Program of China/ ; XDB30000000//the Strategic Priority Research Program of the Chinese Academy of Sciences/ ; 23XD1420200//the Program of Shanghai Academic Research Leaders/ ; DP2020036//the Chong-qing Bayu Scholar Program/ ; 2023M730635//the China Postdoctoral Science Foundation/ ; T2425006//National Science Fund for Distinguished Young Scholars/ ; }, mesh = {*CRISPR-Cas Systems/genetics ; Humans ; Electrochemical Techniques ; Amyotrophic Lateral Sclerosis/diagnosis/genetics ; }, abstract = {The CRISPR/Cas system is a powerful genome editing tool and possesses widespread applications in molecular diagnostics, therapeutics and genetic engineering. But easy folding of the target sequences causes remarkable deterioration of the recognition and shear efficiency in the case of single Cas-CRISPR RNA (crRNA) duplex. Here, we develop a CRISPR/Cas cooperative shearing (CRISPR-CS) system. Compared with traditional CRISPR/Cas system, two CRISPR/Cas-crRNA duplexes simultaneously recognize different sites in the target sequence, increasing recognition possibility and shearing efficiency. Cooperative shearing cuts more methylene blue-ssDNA reporters on the electrode, enabling unamplified nucleic acid electrochemical assay in less than 5 minutes with a detection limit of 9.5×10[-20] M, 2 to 9 orders of magnitude lower than those of other electrochemical assays. The CRISPR-CS platform detects monkeypox, human papilloma virus and amyotrophic lateral sclerosis with an accuracy up to 98.1 %, demonstrating the potential application of the efficient cooperative shearing.}, } @article {pmid39393594, year = {2024}, author = {Coppieters, R and Bouzigues, A and Jiskoot, L and Montembeault, M and Tee, BL and , and Rohrer, JD and Bruffaerts, R}, title = {A systematic review of the quantitative markers of speech and language of the frontotemporal degeneration spectrum and their potential for cross-linguistic implementation.}, journal = {Neuroscience and biobehavioral reviews}, volume = {167}, number = {}, pages = {105909}, doi = {10.1016/j.neubiorev.2024.105909}, pmid = {39393594}, issn = {1873-7528}, mesh = {Humans ; *Frontotemporal Dementia/physiopathology/diagnosis ; *Speech/physiology ; Linguistics ; Language ; Biomarkers ; }, abstract = {Frontotemporal dementia (FTD) is a neurodegenerative disease spectrum with an urgent need for reliable biomarkers for early diagnosis and monitoring. Speech and language changes occur in the early stages of FTD and offer a potential non-invasive, early, and accessible diagnostic tool. The use of speech and language markers in this disease spectrum is limited by the fact that most studies investigate English-speaking patients. This systematic review examines the literature on psychoacoustic and linguistic features of speech that occur across the FTD spectrum across as many different languages as possible. 76 papers were identified that investigate psychoacoustic and linguistic markers in discursive speech. 75 % of these papers studied English-speaking patients. The most generalizable features found across different languages, are speech rate, articulation rate, pause frequency, total pause duration, noun-verb ratio, and total number of nouns. While there are clear interlinguistic differences across patient groups, the results show promise for implementation of cross-linguistic markers of speech and language across the FTD spectrum particularly for psychoacoustic features.}, } @article {pmid39393030, year = {2024}, author = {Aamodt, WW and Sun, C and Dahodwala, N and Elser, H and Schneider, ALC and Farrar, JT and Coe, NB and Willis, AW}, title = {End-of-Life Health Care Service Use and Cost Among Medicare Decedents With Neurodegenerative Diseases.}, journal = {Neurology}, volume = {103}, number = {9}, pages = {e209925}, pmid = {39393030}, issn = {1526-632X}, support = {K23 AG086669/AG/NIA NIH HHS/United States ; L30 AG089647/AG/NIA NIH HHS/United States ; }, mesh = {Humans ; United States ; Male ; Female ; *Medicare/economics/statistics & numerical data ; Aged ; Retrospective Studies ; *Terminal Care/economics/statistics & numerical data ; Aged, 80 and over ; *Neurodegenerative Diseases/economics/therapy/epidemiology ; Patient Acceptance of Health Care/statistics & numerical data ; Health Care Costs/statistics & numerical data ; Emergency Service, Hospital/statistics & numerical data/economics ; Parkinson Disease/economics/therapy/epidemiology ; Hospice Care/economics/statistics & numerical data ; Alzheimer Disease/economics/therapy/epidemiology ; Amyotrophic Lateral Sclerosis/economics/therapy/epidemiology ; }, abstract = {BACKGROUND AND OBJECTIVES: Although neurodegenerative diseases are a leading cause of death, little is known about health care utilization and cost during the end-of-life (EoL) period or how it compares with that of other life-limiting conditions. We aimed to describe and compare resource utilization among US Medicare decedents with neurodegenerative diseases with decedents with cancer.

METHODS: We conducted a retrospective study of Medicare Part A and B beneficiaries with Alzheimer disease (AD), Parkinson disease (PD), or amyotrophic lateral sclerosis (ALS) who died in 2018. Decedents diagnosed with malignant brain tumors or pancreatic cancer served as non-neurodegenerative comparators. Descriptive analyses examined demographic and clinical characteristics in the last year of life. The probabilities and associated costs of emergency department (ED), inpatient, skilled nursing facility (SNF), and hospice utilization during the last 12 and 6 months of life were also compared between persons with neurodegenerative diseases and cancer, adjusting for sociodemographic factors and comorbidity burden.

RESULTS: A total of 1,126,799 Medicare beneficiaries died in 2018, of which 357,926 had a qualifying diagnosis. Persons with neurodegenerative diseases were older and more frequently received Medicaid assistance than persons with brain or pancreatic cancer. In all groups, health care service utilization increased over the last year of life, and total costs were predominantly attributable to inpatient care. In the last 6 months of life, neurologist care was infrequent among patients with neurodegenerative disease (AD: 1.5%; PD: 8.6%; ALS: 32.0%). Persons with neurodegenerative diseases as compared to persons with malignant brain tumors also had greater odds of ED use (AD: adjusted odds ratio [aOR] 1.17, 95% CI 1.11-1.23; PD: aOR 1.18, 95% CI 1.11-1.25; ALS: aOR 1.11, 95% CI 1.01-1.23), lower odds of hospitalization (AD: aOR 0.64, 95% CI 0.60-0.68; PD: aOR 0.65, 95% CI 0.61-0.69; ALS: aOR 0.33, 95% CI 0.30-0.37), and lower odds of hospice enrollment (AD: aOR 0.33, 95% CI 0.31-0.36; PD: aOR 0.33, 95% CI 0.31-0.36; ALS: aOR 0.41, 95% CI 0.36-0.46). The findings were similar in pancreatic cancer.

DISCUSSION: Persons with neurodegenerative diseases in the United States are more likely to visit the ED and less likely to use inpatient and hospice services at EoL than persons with brain or pancreatic cancer. These group differences may stem from prognostic uncertainty and reflect inadequate EoL care practices, requiring further investigation to ensure more timely palliative care and hospice referrals.}, } @article {pmid39392186, year = {2025}, author = {Corcia, P and Piras, R and Lunetta, C}, title = {Why is the treatment and management of amyotrophic lateral sclerosis so difficult?.}, journal = {Expert review of neurotherapeutics}, volume = {25}, number = {1}, pages = {1-3}, doi = {10.1080/14737175.2024.2415002}, pmid = {39392186}, issn = {1744-8360}, } @article {pmid39392096, year = {2024}, author = {}, title = {Correction to "Differential activation of neuronal and glial STAT3 in the spinal cord of the SOD1G93A mouse model of amyotrophic lateral sclerosis".}, journal = {The European journal of neuroscience}, volume = {60}, number = {8}, pages = {6125-6126}, doi = {10.1111/ejn.16562}, pmid = {39392096}, issn = {1460-9568}, } @article {pmid39391721, year = {2024}, author = {Hodgson, RE and Rayment, JA and Huang, WP and Sanchez Avila, A and Ellis, BCS and Lin, YH and Soni, N and Hautbergue, GM and Shelkovnikova, TA}, title = {C9orf72 poly-PR forms anisotropic condensates causative of nuclear TDP-43 pathology.}, journal = {iScience}, volume = {27}, number = {10}, pages = {110937}, pmid = {39391721}, issn = {2589-0042}, support = {MR/W028522/1/MRC_/Medical Research Council/United Kingdom ; }, abstract = {Proteinaceous inclusions formed by C9orf72-derived dipeptide-repeat (DPR) proteins are a histopathological hallmark in ∼50% of familial amyotrophic lateral sclerosis/frontotemporal dementia (ALS/FTD) cases. However, DPR aggregation/inclusion formation could not be efficiently recapitulated in cell models for four out of five DPRs. In this study, using optogenetics, we achieved chemical-free poly-PR condensation/aggregation in cultured cells including human motor neurons, with spatial and temporal control. Strikingly, nuclear poly-PR condensates had anisotropic, hollow-center appearance, resembling TDP-43 anisosomes, and their growth was limited by RNA. These condensates induced abnormal TDP-43 granulation in the nucleus without stress response activation. Cytoplasmic poly-PR aggregates forming under prolonged opto-stimulation were more persistent than its nuclear condensates, selectively sequestered TDP-43 in a demixed state and surrounded spontaneous stress granules. Thus, poly-PR condensation accompanied by nuclear TDP-43 dysfunction may constitute an early pathological event in C9-ALS/FTD. Anisosome-type condensates of disease-linked proteins may represent a common molecular species in neurodegenerative disease.}, } @article {pmid39391382, year = {2024}, author = {Osaro, E and Fajardo-Rojas, F and Cooper, GM and Gómez-Gualdrón, D and Colón, YJ}, title = {Active learning of alchemical adsorption simulations; towards a universal adsorption model.}, journal = {Chemical science}, volume = {15}, number = {42}, pages = {17671-17684}, pmid = {39391382}, issn = {2041-6520}, abstract = {Adsorption is a fundamental process studied in materials science and engineering because it plays a critical role in various applications, including gas storage and separation. Understanding and predicting gas adsorption within porous materials demands comprehensive computational simulations that are often resource intensive, limiting the identification of promising materials. Active learning (AL) methods offer an effective strategy to reduce the computational burden by selectively acquiring critical data for model training. Metal-organic frameworks (MOFs) exhibit immense potential across various adsorption applications due to their porous structure and their modular nature, leading to diverse pore sizes and chemistry that serve as an ideal platform to develop adsorption models. Here, we demonstrate the efficacy of AL in predicting gas adsorption within MOFs using "alchemical" molecules and their interactions as surrogates for real molecules. We first applied AL separately to each MOF, reducing the training dataset size by 57.5% while retaining predictive accuracy. Subsequently, we amalgamated the refined datasets across 1800 MOFs to train a multilayer perceptron (MLP) model, successfully predicting adsorption of real molecules. Furthermore, by integrating MOF features into the AL framework using principal component analysis (PCA), we navigated MOF space effectively, achieving high predictive accuracy with only a subset of MOFs. Our results highlight AL's efficiency in reducing dataset size, enhancing model performance, and offering insights into adsorption phenomenon in large datasets of MOFs. This study underscores AL's crucial role in advancing computational material science and developing more accurate and less data intensive models for gas adsorption in porous materials.}, } @article {pmid39390888, year = {2024}, author = {Boran, HE and Kılınç, H and Kurtkaya Koçak, Ö and Yanık, E and Kuruoğlu, HR and Cengiz, B}, title = {Somatosensory temporal discrimination analysis reveals impaired processing in amyotrophic lateral sclerosis.}, journal = {Muscle & nerve}, volume = {70}, number = {6}, pages = {1257-1262}, doi = {10.1002/mus.28278}, pmid = {39390888}, issn = {1097-4598}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology/diagnosis ; Male ; Female ; Middle Aged ; *Evoked Potentials, Somatosensory/physiology ; Aged ; *Somatosensory Cortex/physiopathology ; Adult ; Hand/physiopathology ; Sensory Thresholds/physiology ; }, abstract = {INTRODUCTION/AIMS: While amyotrophic lateral sclerosis (ALS) is primarily characterized as a motor system disorder, there is a growing body of evidence indicating sensory involvement. This study aimed to examine the hypothesis that somatosensory processing is impaired in ALS.

METHODS: Study participants were ALS patients followed at the Neuromuscular Outpatient Unit, as well as healthy volunteers, from March 2021 to July 2023. The Medical Research Council (MRC) sum score was calculated for nine muscle groups bilaterally. The clinical status of patients was evaluated with the ALS Functional Rating Scale-Revised (ALSFRS-R) and the Penn Upper Motor Neuron core. Somatosensory temporal discrimination thresholds (STDTs) were recorded on the medial and lateral parts of both hands. Somatosensory cortex excitability was investigated with the paired somatosensory evoked potentials (SEP) paradigm in a subgroup.

RESULTS: Increased STD values were detected in ALS patients compared to controls in both medial (107.66 ± 35 ms vs. 82.7 ± 32.5 ms, p = .001) and lateral (106.5 ± 34.5 ms vs. 82.9 ± 31.3 ms, p = .002) hands. There were no significant differences in STDTs among ALS patients across four regions (medial and lateral parts of the right and left hands). Amplitude ratios obtained from the paired-pulse SEP paradigm were approximately 1 for all interstimulus intervals (ISIs). STDTs did not show any correlations with motor findings or scales.

DISCUSSION: Somatosensory processing appears to be compromised among ALS patients. The lack of correlation between impaired STDT and motor findings implies that it is a purely sensory deficit in ALS.}, } @article {pmid39390661, year = {2024}, author = {Howard, IM and Babu, S and Carter, C and Sakowski, SA and Kurent, JE and Cudkowicz, ME and Feldman, EL}, title = {Priorities and Recommendations to Make ALS a Livable Disease Emanating from the 2024 National Academies of Sciences, Engineering, and Medicine Report Living with ALS.}, journal = {Annals of neurology}, volume = {96}, number = {6}, pages = {1035-1039}, pmid = {39390661}, issn = {1531-8249}, support = {R01 TS000327/TS/ATSDR CDC HHS/United States ; OT2 NS136938/NS/NINDS NIH HHS/United States ; U01 NS077179/NS/NINDS NIH HHS/United States ; U01 NS136020/NS/NINDS NIH HHS/United States ; //Charles H. Abdalian, Jr. ALS Research Fund/ ; OT2 NS136939/NS/NINDS NIH HHS/United States ; //NeuroNetwork for Emerging Therapies/ ; R01 ES030049/ES/NIEHS NIH HHS/United States ; R01TS000344//Centers for Disease Control and Prevention/Agency for Toxic Substances and Disease Registry/ ; //American Academy of Neurology/ ; //ALS One/ ; //ALS Association/ ; UF1 NS131791/NS/NINDS NIH HHS/United States ; R01TS000327//Centers for Disease Control and Prevention/Agency for Toxic Substances and Disease Registry/ ; 1U01NS136021-01/NH/NIH HHS/United States ; 1U01NS136020-01/NH/NIH HHS/United States ; R01NS127188/NH/NIH HHS/United States ; R01ES030049/NH/NIH HHS/United States ; //Scott L. Pranger/ ; //The Sean M. Healey & AMG Center for ALS/ ; 1U01NS077179-01/NH/NIH HHS/United States ; //Muscular Dystrophy Association/ ; U01 NS136021/NS/NINDS NIH HHS/United States ; R01 NS127188/NS/NINDS NIH HHS/United States ; //The Neurological Clinical Research Institute/ ; UF1NS131791-01/NH/NIH HHS/United States ; 1OT2NS136938-1/NH/NIH HHS/United States ; R01 TS000344/TS/ATSDR CDC HHS/United States ; //ALS Finding a Cure/ ; OT2NS136939/NH/NIH HHS/United States ; }, mesh = {*Amyotrophic Lateral Sclerosis/therapy/diagnosis ; Humans ; United States ; Quality of Life ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a relentless, fatal neurodegenerative disease. The progressive loss of voluntary muscle function, diagnostic delays, lack of effective treatments, and challenges accessing multidisciplinary care and resources have tremendous impact on quality of life. The congressionally directed ALS committee of the National Academies of Science, Engineering, and Medicine, in their 2024 report "Living with ALS," recommends critical actions for specific United States stakeholders to make ALS a livable disease over the next decade. This review summarizes the context and recommendations of the report. Advocacy efforts are critical to make these recommendations a reality for the ALS community. ANN NEUROL 2024;96:1035-1039.}, } @article {pmid39390590, year = {2024}, author = {Vanderhaeghe, S and Prerad, J and Tharkeshwar, AK and Goethals, E and Vints, K and Beckers, J and Scheveneels, W and Debroux, E and Princen, K and Van Damme, P and Fivaz, M and Griffioen, G and Van Den Bosch, L}, title = {A pathogenic mutation in the ALS/FTD gene VCP induces mitochondrial hypermetabolism by modulating the permeability transition pore.}, journal = {Acta neuropathologica communications}, volume = {12}, number = {1}, pages = {161}, pmid = {39390590}, issn = {2051-5960}, support = {HBC.2019.2575//VLAIO Baekeland mandate/ ; 030383//Flanders Innovation & Entrepreneurship (VLAIO)/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology ; *Valosin Containing Protein/genetics/metabolism ; Humans ; *Frontotemporal Dementia/genetics/metabolism/pathology ; *Mitochondria/metabolism/pathology ; *Mitochondrial Permeability Transition Pore/metabolism ; *Mutation ; Cell Line, Tumor ; Membrane Potential, Mitochondrial/genetics ; Mitochondrial Membrane Transport Proteins/genetics/metabolism ; Calcium/metabolism ; }, abstract = {Valosin-containing protein (VCP) is a ubiquitously expressed type II AAA[+] ATPase protein, implicated in both amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). This study aimed to explore the impact of the disease-causing VCP[R191Q/wt] mutation on mitochondrial function using a CRISPR/Cas9-engineered neuroblastoma cell line. Mitochondria in these cells are enlarged, with a depolarized mitochondrial membrane potential associated with increased respiration and electron transport chain activity. Our results indicate that mitochondrial hypermetabolism could be caused, at least partially, by increased calcium-induced opening of the permeability transition pore (mPTP), leading to mild mitochondrial uncoupling. In conclusion, our findings reveal a central role of the ALS/FTD gene VCP in maintaining mitochondrial homeostasis and suggest a model of pathogenesis based on progressive alterations in mPTP physiology and mitochondrial energetics.}, } @article {pmid39390534, year = {2024}, author = {Xu, M and Li, B and Li, C and Chai, P and Qiu, Q and Zheng, Z and Chen, Q and Luo, D and Xu, X and Zhou, C}, title = {Is longer axial length protective of vision-threatening diabetic retinopathy across different ages? A multicenter cohort of 736 patients.}, journal = {International journal of retina and vitreous}, volume = {10}, number = {1}, pages = {74}, pmid = {39390534}, issn = {2056-9920}, support = {22QA1407500//Shanghai Science and Technology Development Foundation/ ; SHWSRS [2022-65]//Shanghai Rising Stars of Medical Talent Youth Development Program/ ; CTCCR-2021C01//Clinical Research Innovation Plan of Shanghai General Hospital/ ; 82471104//National Natural Science Foundation of China/ ; }, abstract = {PURPOSE: Vision-threatening diabetic retinopathy (VTDR) included severe non-proliferative diabetic retinopathy (NPDR), proliferative diabetic retinopathy (PDR) and clinically significant diabetic macular edema (DME). To compare the axial length (AL) and assess its influence on VTDR across different ages.

METHODS: A retrospective cohort study. Medical chart review was performed in 736 consecutive patients with VTDR. The patients were divided into young (≤ 45 years) and elderly group (> 45 years) based on their age at the diagnosis of VTDR. After at least one year of standardized treatments, all eligible patients were followed up. The main outcome measures included the presence of tractional retinal detachment (TRD) involving foveal, final best-corrected visual acuity (BCVA), the development of neovascular glaucoma (NVG), and recurrent vitreous hemorrhage (VH) post-vitrectomy. ALs were compared between two age groups. The impact of AL on clinical outcomes was determined by logistic analyses after controlling for systemic parameters.

RESULTS: The study included 144 patients ≤ 45 years and 592 patients > 45 years. Young patients had significantly longer AL than elderly participants (23.9 mm vs 23.0 mm, p < 0.001). Over a median follow-up of 25.9 months, a larger proportion of young patients developed TRD (34.7% vs 16.2%, p < 0.001) and recurrent VH (18.6% vs 10.3%, p = 0.040) than elderly patients. In elderly group, longer AL is an independent protective factor in preventing TRD (odds ratio [OR], 0.5; 95% confidence interval [CI], 0.4-0.7; P < 0.001). However, this beneficial effect was not observed in young patients.

CONCLUSIONS: Young patients with VTDR exhibited significantly longer AL but more aggressive clinical signs with compromised prognosis. In elderly group, a longer AL independently reduced the risk of TRD, while this protective effect did not exist for young patients.}, } @article {pmid39389966, year = {2024}, author = {Kamemura, K and Kozono, R and Tando, M and Okumura, M and Koga, D and Kusumi, S and Tamai, K and Okumura, A and Sekine, S and Kamiyama, D and Chihara, T}, title = {Secretion of endoplasmic reticulum protein VAPB/ALS8 requires topological inversion.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {8777}, pmid = {39389966}, issn = {2041-1723}, support = {P40 OD010949/OD/NIH HHS/United States ; R01 NS107558/NS/NINDS NIH HHS/United States ; 21K18236//MEXT | Japan Society for the Promotion of Science (JSPS)/ ; 21H02479//MEXT | Japan Society for the Promotion of Science (JSPS)/ ; }, mesh = {*Endoplasmic Reticulum/metabolism ; Humans ; Animals ; *Amyotrophic Lateral Sclerosis/metabolism/genetics ; *Vesicular Transport Proteins/metabolism/genetics ; Cell Membrane/metabolism ; Mutation ; Protein Domains ; Membrane Proteins/metabolism/genetics ; HEK293 Cells ; Matrix Metalloproteinase 1/metabolism/genetics ; Protein Transport ; }, abstract = {VAMP-associated protein (VAP) is a type IV integral transmembrane protein at the endoplasmic reticulum (ER). Mutations in human VAPB/ALS8 are associated with amyotrophic lateral sclerosis (ALS). The N-terminal major sperm protein (MSP) domain of VAPB (Drosophila Vap33) is cleaved, secreted, and acts as a signaling ligand for several cell-surface receptors. Although extracellular functions of VAPB are beginning to be understood, it is unknown how the VAPB/Vap33 MSP domain facing the cytosol is secreted to the extracellular space. Here we show that Vap33 is transported to the plasma membrane, where the MSP domain is exposed extracellularly by topological inversion. The externalized MSP domain is cleaved by Matrix metalloproteinase 1/2 (Mmp1/2). Overexpression of Mmp1 restores decreased levels of extracellular MSP domain derived from ALS8-associated Vap33 mutants. We propose an unprecedented secretion mechanism for an ER-resident membrane protein, which may contribute to ALS8 pathogenesis.}, } @article {pmid39389563, year = {2025}, author = {Feindt, B and Roth, A and Heyde, CE and Behrens, J and Feist, B and Kasprick, L and Sultzer, R and Baerwald, C}, title = {GeriNOT in the Surgical Inpatient Setting.}, journal = {Zeitschrift fur Orthopadie und Unfallchirurgie}, volume = {163}, number = {2}, pages = {137-145}, doi = {10.1055/a-2343-4014}, pmid = {39389563}, issn = {1864-6743}, mesh = {Humans ; Female ; Aged ; Male ; Aged, 80 and over ; *Geriatric Assessment/methods/statistics & numerical data ; Germany/epidemiology ; Retrospective Studies ; *Femoral Fractures/surgery/epidemiology/diagnosis ; Hip Fractures/surgery/epidemiology ; *Spinal Fractures/surgery/epidemiology/diagnosis ; }, abstract = {Die Richtlinie des Gemeinsamen Bundesausschusses (G-BA) über Maßnahmen zur Qualitätssicherung zur Versorgung von Patient*innen mit hüftgelenknaher Femurfraktur verpflichtet Krankenhäuser zum Einsatz eines validierten geriatrischen Screeninginstruments. Die systematische Anwendung des GeriNOT mit prozessproduzierter Datenerhebung im Akutaufnahmeprozess durch Integration in das Krankenhausinformationssystem (KIS) ermöglicht die Identifikation von Risikopotenzialen auch in anderen geriatrischen Diagnosegruppen.Mit Einbindung des GeriNOT in den Akutaufnahmeprozess wurde geprüft, ob auch andere vulnerable geriatrische Diagnosegruppen von einer frühzeitig eingeleiteten Risikoidentifikation profitieren können.Datengrundlage dieser Untersuchung bildete eine retrospektive bizentrische Erhebung elektronischer Fallakten (Mai 2014 bis April 2015, n = 3443). Aus diesem Primärdatensatz wurde die Subgruppe stationärer Akutaufnahmen (n = 821) der Orthopädie/Unfallchirurgie eines Zentrums in Bezug auf die Endpunkte "Inanspruchnahme bedarfsgerechter poststationärer Pflegeleistungen" und "Neueinzug in stationäre Dauer-/Kurzzeitpflege" analysiert. Es wurden Prädiktionskraft und Klassifikationsgenauigkeit von GeriNOT dieser ab 70-jährigen Personen in Diagnosegruppen für die definierten Endpunkte beurteilt: Akutaufnahmen insgesamt, Frakturen insgesamt, hüftgelenknahe Femurfraktur und Wirbelsäulenerkrankungen inklusive Wirbelsäulenfrakturen.Im Untersuchungszeitraum wurden 821 Personen akutstationär aufgenommen. Das mittlere Alter betrug 81,4 ± 6,8 Jahre (n = 821; 68,1% Frauen, 31,9% Männer). Folgende Diagnosegruppen wurden gebildet und analysiert: Frakturen insgesamt (n = 490), Wirbelsäulenerkrankungen (n = 265), davon Wirbelsäulenfrakturen (n = 174), hüftgelenknahe Femurfraktur (n = 108). In der Gesamtgruppe (n = 821; MW = 4,279; SD = 2,180) und in den Diagnosegruppen lag der Mittelwert des GeriNOT-Scores über dem Schwellenwert ≥ 4. In der Gruppe der hüftgelenknahen Femurfraktur wurde der höchste Wert ermittelt (MW = 4,852; SD = 2,022), der niedrigste in der Gruppe der Wirbelsäulenfrakturen (MW = 4,177; SD = 2,171). In der Aufnahmesituation bez. behandlungsbedürftiger Diagnosen, Polypharmazie und bereits in Anspruch genommener Pflegeleistungen unterschieden sich die Diagnosegruppen nur geringfügig. Einweisungen aus stationärer Kurz- und Dauerpflege erfolgten in der Gesamtgruppe (n = 821) in 16,44% der Fälle, am häufigsten mit 31,48% in der Gruppe der hüftgelenknahen Femurfraktur, hingegen am seltensten in der Diagnosegruppe der Wirbelsäulenerkrankungen mit 6,79%. GeriNOT detektierte für diese Gruppe ein erhöhtes Risiko in Bezug auf die definierten Endpunkte. Nur 4,26% aller Patient*innen mit identifiziertem geriatrischen Risikopotenzial wurden akutgeriatrisch weiterversorgt.Die Ergebnisse zeigten ein erhöhtes geriatrisches Risiko in allen analysierten Diagnosegruppen, am stärksten innerhalb der Gruppe der Wirbelsäulenerkrankungen. Der KIS-gestützte Einsatz des GeriNOT initiiert die systematische Risikoidentifikation im akutstationären Aufnahmemanagement. Die fallbegleitende Ergebnisvisualisierung in den KIS-Arbeitsplätzen könnte als Ausgangspunkt für die nachfolgende Anwendung von Assessmentinstrumenten und risikoadjustierter Behandlungspfade genutzt werden. Mit diesen Erkenntnissen könnte das Patientenoutcome potenziell positiv beeinflusst werden.}, } @article {pmid39386562, year = {2024}, author = {Dargan, R and Mikheenko, A and Johnson, NL and Packer, B and Li, Z and Craig, EJ and Sarbanes, SL and Bereda, C and Mehta, PR and Keuss, M and Nalls, MA and Qi, YA and Weller, CA and Fratta, P and Ryan, VH}, title = {Altered mRNA transport and local translation in iNeurons with RNA binding protein knockdown.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {39386562}, issn = {2692-8205}, support = {ZIA AG000547/ImNIH/Intramural NIH HHS/United States ; }, abstract = {Neurons rely on mRNA transport and local translation to facilitate rapid protein synthesis in processes far from the cell body. These processes allow precise spatial and temporal control of translation and are mediated by RNA binding proteins (RBPs), including those known to be associated with neurodegenerative diseases. Here, we use proteomics, transcriptomics, and microscopy to investigate the impact of RBP knockdown on mRNA transport and local translation in iPSC-derived neurons. We find thousands of transcripts enriched in neurites and that many of these transcripts are locally translated, possibly due to the shorter length of transcripts in neurites. Loss of frontotemporal dementia/amyotrophic lateral sclerosis (FTD/ALS)-associated RBPs TDP-43 and hnRNPA1 lead to distinct alterations in the neuritic proteome and transcriptome. TDP-43 knockdown (KD) leads to increased neuritic mRNA and translation. In contrast, hnRNPA1 leads to increased neuritic mRNA, but not translation, and more moderate effects on local mRNA profiles, possibly due to compensation by hnRNPA3. These results highlight the crucial role of FTD/ALS-associated RBPs in mRNA transport and local translation in neurons and the importance of these processes in neuron health and disease.}, } @article {pmid39386496, year = {2024}, author = {El-Khatib, SM and Vagadia, AR and Le, ACD and Ng, DQ and Baulch, JE and Du, M and Tan, Z and Xu, X and Chan, A and Acharya, MM}, title = {BDNF augmentation reverses cranial radiation therapy-induced cognitive decline and neurodegenerative consequences.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2024.09.23.614590}, pmid = {39386496}, issn = {2692-8205}, support = {R01 CA276212/CA/NCI NIH HHS/United States ; }, abstract = {Cranial radiation therapy (RT) for brain cancers is often associated with the development of radiation-induced cognitive dysfunction (RICD). RICD significantly impacts the quality of life for cancer survivors, highlighting an unmet medical need. Previous human studies revealed a marked reduction in plasma brain-derived neurotrophic factor (BDNF) post-chronic chemotherapy, linking this decline to a substantial cognitive dysfunction among cancer survivors. Moreover, riluzole (RZ)-mediated increased BDNF in vivo in the chemotherapy-exposed mice reversed cognitive decline. RZ is an FDA-approved medication for ALS known to increase BDNF in vivo . In an effort to mitigate the detrimental effects of RT-induced BDNF decline in RICD, we tested the efficacy of RZ in a cranially irradiated (9 Gy) adult mouse model. Notably, RT-exposed mice exhibited significantly reduced hippocampal BDNF, accompanied by increased neuroinflammation, loss of neuronal plasticity-related immediate early gene product, cFos, and synaptic density. Spatial transcriptomic profiling comparing the RT+Veh with the RT+RZ group showed gene expression signatures of neuroprotection of hippocampal excitatory neurons post-RZ. RT-exposed mice performed poorly on learning and memory, and memory consolidation tasks. However, irradiated mice receiving RZ (13 mg/kg, drinking water) for 6-7 weeks showed a significant improvement in cognitive function compared to RT-exposed mice receiving vehicle. Dual-immunofluorescence staining, spatial transcriptomics, and biochemical assessment of RZ-treated irradiated brains demonstrated preservation of synaptic integrity and neuronal plasticity but not neurogenesis and reduced neuroinflammation concurrent with elevated BDNF levels and transcripts compared to vehicle-treated irradiated brains. In summary, oral administration of RZ represents a viable and translationally feasible neuroprotective approach against RICD.}, } @article {pmid39386447, year = {2024}, author = {Rodemer, W and Ra, I and Jia, E and Gujral, J and Zhang, B and Hoxha, K and Xing, B and Mehta, S and Farag, M and Porta, S and Jensen, FE and Talos, DM and Lee, VM}, title = {Hyperexcitability precedes CA3 hippocampal neurodegeneration in a dox-regulatable TDP-43 mouse model of ALS-FTD.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2024.09.24.612703}, pmid = {39386447}, issn = {2692-8205}, support = {R01 NS101156/NS/NINDS NIH HHS/United States ; }, abstract = {UNLABELLED: Neuronal hyperexcitability is a hallmark of amyotrophic lateral sclerosis (ALS) but its relationship with the TDP-43 aggregates that comprise the predominant pathology in over 90% of ALS cases remains unclear. Emerging evidence in tissue and slice culture models indicate that TDP-43 pathology induces neuronal hyperexcitability suggesting it may be responsible for the excitotoxicity long believed to be a major driver of ALS neuron death. Here, we characterized hyperexcitability and neurodegeneration in the hippocampus of doxycycline-regulatable rNLS8 mice (NEFH-tTA x tetO-hTDP-43ΔNLS), followed by treatment with AAV encoded DREADDs and anti-seizure medications to measure the effect on behavioral function and neurodegeneration. We found that approximately half of the CA3 neurons in the dorsal hippocampus are lost between 4 and 6 weeks after TDP-43ΔNLS induction. Neurodegeneration was preceded by selective hyperexcitability in the mossy fiber - CA3 circuit, leading us to hypothesize that glutamate excitotoxicity may be a significant contributor to neurodegeneration in this model. Interestingly, hippocampal injection of AAV encoded inhibitory DREADDs (hM4Di) and daily activation with CNO ligand rescued anxiety deficits on elevated zero maze (EZM) but did not reduce neurodegeneration. Therapeutic doses of the anti-seizure medications, valproic acid and levetiracetam, did not improve behavior or prevent neurodegeneration. These results highlight the complexity of TDP-43 - induced alterations to neuronal excitability and suggest that whereas targeting hyperexcitability can meliorate some behavioral deficits, it may not be sufficient to halt or slow neurodegeneration in TDP-43-related proteinopathies.

SIGNIFICANCE STATEMENT: Cytoplasmic aggregates of TAR DNA Binding Protein 43 (TDP-43) are the predominant pathology in over 90% of Amyotrophic lateral sclerosis (ALS) and the majority of frontotemporal lobar degeneration (FTLD-TDP) cases. Understanding how TDP-43 pathology promotes neurodegeneration may lead to therapeutic strategies to slow disease progression in humans. Recent reports in mouse and cell culture models suggest loss-of-normal TDP-43 function may drive neuronal hyperexcitability, a key physiological hallmark of ALS and possible contributor to neurodegeneration. In this study, we identified region-specific hyperexcitability that precedes neurodegeneration in the inducible rNLS8 TDP-43 mouse model. Suppressing hyperexcitability with chemogenetics improved behavioral function but did not reduce hippocampal neuron loss. Anti-seizure medications had no beneficial effects suggesting directly targeting hyperexcitability may not be therapeutically effective.}, } @article {pmid39386324, year = {2024}, author = {Ross, CW and Loudermilk, EL and O'Brien, JJ and Snitker, G}, title = {Lidar-derived structural-complexity data across four experimental forests.}, journal = {Data in brief}, volume = {57}, number = {}, pages = {110955}, pmid = {39386324}, issn = {2352-3409}, abstract = {Structural complexity refers to the three-dimensional arrangement and variability of both biotic and abiotic components of an ecosystem. Metrics that characterize structural complexity are often used to manage various aspects of ecosystem function, such as light transmittance, wildlife habitat, and biological diversity. Additionally, these metrics aid in evaluating resilience to disturbance events, including hurricanes, bark-beetle outbreaks, and wildfire. Recent advances in wildland fire modelling have facilitated the integration of forest structural complexity metrics into the QUIC-Fire model, enabling real-time prediction of fire spread and behaviour by simulating interactions between fire, weather, topography, and forest structure. While QUIC-Fire is designed to be highly adaptable, model performance depends on the availability and accuracy of local data inputs. Expanding the model's usability across different regions can be facilitated by the availability of more comprehensive and high-quality data. Thus, the primary goal behind the data products we developed was to establish a basis for collaborative research across various disciplines, particularly within the focal areas of the Southern Research Station, such as forestry, wildland fire, hydrology, soil science, and cultural resources at Bent Creek, Coweeta, Escambia, and Hitchiti Experimental Forests (EFs). Airborne laser scanning (ALS) was used to collect point-cloud data for each EF during the leaf-off season to minimize interference from foliage. Subsequent processing of the raw lidar data involved outlier detection and filtering, ground and non-ground classification, and the computation of a variety of metrics representing various aspects of topography and forest structure at both the pixel-level and the tree-level. Pixel-level topographic data products include: digital elevation model (DEM), slope, aspect, topographic position index (TPI), topographic roughness index (TRI), roughness, and flow direction. Forest structural-complexity metrics include canopy height, foliar height diversity (FHD), vertical distribution ratio (VDR), canopy rugosity, crown relief ratio (CRR), understory complexity index (UCI), vertical complexity index (VCI), canopy cover, mean vegetation height, and the standard deviation of vegetation height. Tree-level data products were computed from the point cloud using multiple algorithms to perform individual tree detection (ITD) and individual tree segmentation (ITS). The datasets have been harmonized and are openly accessible through the USDA Forest Service Research Data Archive.}, } @article {pmid39385824, year = {2024}, author = {Chen, L and Chen, J and Weng, W and Wu, M and Zhou, X and Yan, P}, title = {Bibliometric analysis of microRNAs and Parkinson's disease from 2014 to 2023.}, journal = {Frontiers in neurology}, volume = {15}, number = {}, pages = {1466186}, pmid = {39385824}, issn = {1664-2295}, abstract = {BACKGROUND: Parkinson's disease (PD) is a neurodegenerative disorder characterized by the degeneration of dopaminergic neurons. Recent research has emphasized a significant correlation between microRNAs (miRNAs) and PD. To identify key research areas, provide a comprehensive overview of current research in various fields, and propose potential directions for future studies, a bibliometric analysis was conducted on the involvement of miRNAs in Parkinson's disease from 2014 to 2023.

METHODS: Relevant literature records were collected from the Web of Science Core Collection on February 29, 2024. Subsequently, the data underwent analysis using the Bibliometrix R package and VOSviewer (version 1.6.19).

RESULTS: The annual scientific publications on miRNAs and Parkinson's disease demonstrated an increasing trend, with an annual growth rate of 12.67%. China, the United States, and India emerged as the top three most productive countries/regions. The University of Barcelona had the highest annual publications, followed by Central South University and the Helmholtz Association. The INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES held the top position in terms of H-index and total citations, reflecting its extensive influence and prolific publication output. Kim, J., Junn, E., Hébert, S.S., and Doxakis, E. were the most frequently co-cited authors in the field. Based on the analysis of keywords, the most frequently occurring terms included "alpha-synuclein," "neurodegenerative disease," "exosome," "neuroinflammation," "oxidative stress," "autophagy," and "amyotrophic lateral sclerosis," which have emerged as prominent research topics. Concurrently, there has been notable interest in topics such as "ceRNA," "lncRNAs," "mitochondrial dysfunction," and "circular RNA."

CONCLUSION: This study focused on identifying emerging trends and critical research topics in the bibliometric analysis of microRNAs related to Parkinson's disease. These findings highlight the diverse research landscape and evolving trend of miRNA-related research in PD. The field of miRNA research in Parkinson's disease is actively exploring the underlying mechanisms of miRNA function, identifying potential diagnostic markers, and developing innovative therapeutic strategies. The results of our study offer significant contributions to researchers' ability to track contemporary developments and guide the trajectory of future research in this domain.}, } @article {pmid39385724, year = {2025}, author = {van den Bos, MAJ and Menon, P and Pavey, N and Higashihara, M and Kiernan, MC and Vucic, S}, title = {Direct interrogation of cortical interneuron circuits in amyotrophic lateral sclerosis.}, journal = {Brain : a journal of neurology}, volume = {148}, number = {4}, pages = {1169-1179}, doi = {10.1093/brain/awae317}, pmid = {39385724}, issn = {1460-2156}, support = {//MND Research Australia/ ; #2021/GNT2010812//NHMRC/ ; //Millhouse Foundation/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology/pathology ; Male ; *Interneurons/physiology ; Transcranial Magnetic Stimulation/methods ; Middle Aged ; Female ; Aged ; Electroencephalography/methods ; *Motor Cortex/physiopathology ; Evoked Potentials, Motor/physiology ; Adult ; }, abstract = {Cortical hyperexcitability is a key pathogenic feature of amyotrophic lateral sclerosis (ALS), believed to be mediated through complex interplay of cortical interneurons. To date, there has been no technological approach to facilitate the direct capture of cortical interneuron function. Through combination of transcranial magnetic stimulation (TMS) with advanced EEG, the present study examined GABAergic dysfunction in ALS by recording focused cortical output whilst applying TMS over the primary motor cortex contralateral to the site of symptom onset. Using both a single-pulse and a novel inhibitory paired-pulse paradigm, TMS-EEG studies were undertaken on 21 ALS patients and results compared with healthy controls. TMS responses captured by EEG form a discrete waveform known as the transcranial evoked potential (TEP), with positive (P) or upward deflections occurring at 30 (P30), 60 (P60) and 190 ms (P190) after TMS stimulus. Negative (N) or downward deflections occur at 44 (N44), 100 (N100) and 280 ms (N280) after TMS stimulus. The single-pulse TEPs recorded in ALS patients demonstrated novel differences suggestive of cortical GABAergic dysfunction. When compared with controls, the N100 component was significantly reduced (P < 0.05), whereas the P190 component increased (P < 0.05) in ALS patients. Additionally, the N44 component was correlated with muscle weakness (r = -0.501, P < 0.05). These findings were supported by reduced paired-pulse inhibition of TEP components in ALS patients (P60, P < 0.01; N100, P < 0.005), consistent with dysfunction of cortical interneuronal GABAA-ergic circuits. Furthermore, the reduction in short-interval intracortical inhibition, as reflected by changes in paired-pulse inhibition of the N100 component, was associated with longer disease duration in ALS patients (r = -0.698, P < 0.001). In conclusion, intensive and focused interrogation of the motor cortex using novel TMS-EEG combined technologies has established localized dysfunction of GABAergic circuits, supporting the notion that cortical hyperexcitability is mediated by cortical disinhibition in ALS. Dysfunction of GABAergic circuits was correlated with greater clinical disability and disease duration, implying pathophysiological significance.}, } @article {pmid39385461, year = {2025}, author = {Li, X and Wicks, P and Brown, A and Shivaprasad, A and Greene, M and Crayle, J and Barnes, B and Jhooty, S and Ratner, D and Olby, N and Glass, JD and Jackson, C and Cole, N and Armon, C and Mascias Cadavid, J and Pattee, G and Mcdermott, CJ and Chang, V and Maragakis, N and Bertorini, T and Bowser, R and Bedlack, R}, title = {ALSUntangled #76: Wahls protocol.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {26}, number = {1-2}, pages = {181-185}, doi = {10.1080/21678421.2024.2407407}, pmid = {39385461}, issn = {2167-9223}, mesh = {*Amyotrophic Lateral Sclerosis/diet therapy ; Humans ; Fatty Acids, Omega-3 ; Animals ; *Diet/methods ; }, abstract = {The Wahls diet is a modified Paleolithic diet that emphasizes dark green leafy vegetables, colorful fruits, high-quality animal proteins, and omega-3 polyunsaturated fatty acids, while limiting grains, legumes, dairy products, sugar, and processed foods containing proinflammatory omega-6 fatty acids. The Wahls diet may reduce inflammation, oxidative stress, and mitochondrial dysfunction and has plausible mechanisms for slowing amyotrophic lateral sclerosis (ALS) progression. However, research on its dietary components in the ALS animal models has yielded conflicting results. Though multiple cohort studies suggest high carotenoids, omega-3 fatty acids and fruit intake are associated with reduced ALS risks, neither the diet nor its components has been demonstrated to slow down ALS progression in case studies or clinical trials. On the contrary, the Wahls diet, a restrictive, low-carbohydrate and low glycemic index diet, caused an average weight loss of 7.2% BMI in multiple sclerosis clinical trials, which is a significant concern for people living with amyotrophic lateral sclerosis (PALS) as weight loss is associated with faster ALS progression and shorter survival. Considering the above, we cannot endorse the Wahls diet for slowing ALS progression.}, } @article {pmid39385408, year = {2024}, author = {Shekhar, AC and Alexander, A and Simms, M and Jahan, M and Haugen, A and Lu, M and Ball, R and Clement, J}, title = {Ambulance Transports from NCAA Division 1 Football Games.}, journal = {Prehospital and disaster medicine}, volume = {39}, number = {3}, pages = {266-269}, pmid = {39385408}, issn = {1945-1938}, mesh = {Humans ; *Ambulances ; Male ; Cross-Sectional Studies ; *Football ; Female ; Young Adult ; Minnesota ; Adult ; Emergency Medical Services ; Universities ; Adolescent ; Crowding ; }, abstract = {INTRODUCTION: There is significant public health interest towards providing medical care at mass-gathering events. Furthermore, mass gatherings have the potential to have a detrimental impact on the availability of already-limited municipal Emergency Medical Services (EMS) resources. This study presents a cross-sectional descriptive analysis to report broad trends regarding patients who were transported from National Collegiate Athletic Association (NCAA) Division 1 collegiate football games at a major public university in order to better inform emergency preparedness and resource planning for mass gatherings.

METHODS: Patient care reports (PCRs) from ambulance transports originating from varsity collegiate football games at the University of Minnesota across six years were examined. Pertinent information was abstracted from each PCR.

RESULTS: Across the six years of data, there were a total of 73 patient transports originating from NCAA collegiate football games: 45.2% (n = 33) were male, and the median age was 22 years. Alcohol-related chief complaints were involved in 50.7% (n = 37) of transports. In total, 31.5% of patients had an initial Glasgow Coma Scale (GCS) of less than 15. The majority (65.8%; n = 48; 0.11 per 10,000 attendees) were transported by Basic Life Support (BLS) ambulances. The remaining patients (34.2%; n = 25; 0.06 per 10,000 attendees) were transported by Advanced Life Support (ALS) ambulances and were more likely to be older, have abnormal vital signs, and have a lower GCS.

CONCLUSIONS: This analysis of ambulance transports from NCAA Division 1 collegiate football games emphasizes the prevalence of alcohol-related chief complaints, but also underscores the likelihood of more life-threatening conditions at mass gatherings. These results and additional research will help inform emergency preparedness at mass-gathering events.}, } @article {pmid39382075, year = {2025}, author = {Liang, B and Khan, M and Storts, H and Zhang, EH and Zheng, X and Xing, X and Claybon, H and Wilson, J and Li, C and Jin, N and Fishel, R and Miles, WO and Wang, JJ}, title = {Riluzole Enhancing Anti-PD-1 Efficacy by Activating cGAS/STING Signaling in Colorectal Cancer.}, journal = {Molecular cancer therapeutics}, volume = {24}, number = {1}, pages = {131-140}, pmid = {39382075}, issn = {1538-8514}, support = {R01 CA251753/CA/NCI NIH HHS/United States ; R01 CA208063/CA/NCI NIH HHS/United States ; R01CA215389//National Cancer Institute (NCI)/ ; P30 CA016058/CA/NCI NIH HHS/United States ; R01 CA215389/CA/NCI NIH HHS/United States ; R01 CA067007/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; *Nucleotidyltransferases/metabolism ; *Colorectal Neoplasms/drug therapy/metabolism/pathology ; Mice ; *Membrane Proteins/metabolism ; Humans ; *Signal Transduction/drug effects ; *Programmed Cell Death 1 Receptor/antagonists & inhibitors/metabolism ; *Riluzole/pharmacology/therapeutic use ; CD8-Positive T-Lymphocytes/drug effects/immunology/metabolism ; Cell Line, Tumor ; Immune Checkpoint Inhibitors/pharmacology/therapeutic use ; }, abstract = {Colorectal cancer is the second leading cause of cancer mortality in the United States. Although immune checkpoint blockade therapies including anti-PD-1/PD-L1 have been successful in treating a subset of patients with colorectal cancer, the response rates remain low. We have found that riluzole, a well-tolerated FDA-approved oral medicine for treating amyotrophic lateral sclerosis, increased intratumoral CD8+ T cells and suppressed tumor growth of colon cancer cells in syngeneic immune-competent mice. Riluzole-mediated tumor suppression was dependent on the presence of CD8+ T cells. Riluzole activates the cytosolic DNA sensing cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) pathway in colon cancer cells, resulting in increased expression of IFNβ and IFNβ-regulated genes including CXCL10. Inhibition of ataxia telangiectasia mutated (ATM), but not ATM-related, resulted in a synergistic increase in IFNβ expression, suggesting that riluzole induces ATM-mediated damage response that contributes to cGAS/STING activation. Depletion of cGAS or STING significantly attenuated riluzole-induced expression of IFNβ and CXCL10 as well as increase of intratumoral CD8+ T cells and suppression of tumor growth. These results indicate that riluzole-mediated tumor infiltration of CD8+ T cells and attenuation of tumor growth is dependent on tumor cell-intrinsic STING activation. To determine whether riluzole treatment primes the tumor microenvironment for immune checkpoint modulation, riluzole was combined with anti-PD-1 treatment. This combination showed greater efficacy than either single agent and strongly suppressed tumor growth in vivo. Taken together, our studies indicate that riluzole activates cGAS/STING-mediated innate immune responses, which might be exploited to sensitize colorectal tumors to anti-PD-1/PD-L1 therapies.}, } @article {pmid39381976, year = {2024}, author = {Grassano, M and Moglia, C and Palumbo, F and Koumantakis, E and Cugnasco, P and Callegaro, S and Canosa, A and Manera, U and Vasta, R and De Mattei, F and Matteoni, E and Fuda, G and Salamone, P and Marchese, G and Casale, F and De Marchi, F and Mazzini, L and Mora, G and Calvo, A and Chiò, A}, title = {Reply to "Comprehensive Analysis of Sex Differences in Amyotrophic Lateral Sclerosis Prognosis and Disease Progression".}, journal = {Annals of neurology}, volume = {96}, number = {5}, pages = {1029}, doi = {10.1002/ana.27095}, pmid = {39381976}, issn = {1531-8249}, support = {//ALS Association/ ; //American Brain Foundation/ ; //American Academy of Neurology/ ; }, } @article {pmid39381934, year = {2025}, author = {Calati, R and Tambuzzi, S and Gravagnuolo, R and Muscatiello, L and Magrin, ME and Crippa, F and Madeddu, F and Zoja, R and Gentile, G}, title = {Suicide in prison in the North of Italy (1993-2022): a case-control study examining differences between suicides inside and outside prison.}, journal = {International clinical psychopharmacology}, volume = {40}, number = {5}, pages = {288-294}, doi = {10.1097/YIC.0000000000000569}, pmid = {39381934}, issn = {1473-5857}, mesh = {Humans ; Italy/epidemiology ; Male ; Female ; Adult ; *Prisoners/statistics & numerical data/psychology ; Middle Aged ; Case-Control Studies ; *Suicide/statistics & numerical data/ethnology ; *Prisons/statistics & numerical data ; Risk Factors ; Young Adult ; Substance-Related Disorders/epidemiology ; }, abstract = {Prisoners constitute a group at suicide risk, showing higher relative rates of suicides than the general population. However, there is limited knowledge about the characteristics of those who die by suicide in Italian prisons. Based on the total sample of suicides of the Institute of Forensic Medicine of Milan (1993-2022), suicides in prison (N = 120) were matched by age and gender with cases that occurred outside prison (N = 300) and compared with them. The considered variables were sociodemographic, clinical, and suicide-related. Univariate analyses and logistic regression model were performed. In univariate analyses, suicides in prison showed higher rates of ethnicity different from white Caucasian, lower rates of depression, higher rates of alcoholism, addiction, respiratory system diseases, hepatitis, and amyotrophic lateral sclerosis, lower use of any medication, and in particular psychotropic medications, and a higher percentage of violent suicide method versus nonviolent compared to suicides outside prison. In the logistic regression model, ethnicity, depression, and addiction were the only features differentiating suicides in prison from ones outside prison. Particular attention should be paid to inmates with non-white ethnicity and those with addiction. Ensuring adequate access to psychiatric care and implementing comprehensive suicide prevention strategies within Italian prisons is crucial.}, } @article {pmid39380150, year = {2024}, author = {Meshram, VD and Balaji, R and Saravanan, P and Subbamanda, Y and Deeksha, W and Bajpai, A and Joshi, H and Bhargava, A and Patel, BK}, title = {Computational Insights Into the Mechanism of EGCG's Binding and Inhibition of the TDP-43 Aggregation.}, journal = {Chemical biology & drug design}, volume = {104}, number = {4}, pages = {e14640}, doi = {10.1111/cbdd.14640}, pmid = {39380150}, issn = {1747-0285}, support = {//Science and Engineering Research Board ; Department of Science and Technology/ ; SRG/2022/002109;SERB/CRG/2021/006856//Science Engineering Research Board, Govt. of India/ ; IFA20-PH-256//Deprartment of Science and Technology, Ministry of Science and Technology, Govt. of India, Inspire faculty fellowship/ ; }, mesh = {*Catechin/analogs & derivatives/chemistry/pharmacology/metabolism ; *DNA-Binding Proteins/metabolism/chemistry/antagonists & inhibitors ; Humans ; *Molecular Dynamics Simulation ; *Molecular Docking Simulation ; *Protein Binding ; Binding Sites ; Thermodynamics ; Protein Aggregates/drug effects ; Protein Domains ; }, abstract = {Misfolding and aggregation of TAR DNA-binding protein, TDP-43, is linked to devastating proteinopathies such as ALS. Therefore, targeting TDP-43's aggregation is significant for therapeutics. Recently, green tea polyphenol, EGCG, was observed to promote non-toxic TDP-43 oligomer formation disallowing TDP-43 aggregation. Here, we investigated if the anti-aggregation effect of EGCG is mediated via EGCG's binding to TDP-43. In silico molecular docking and molecular dynamics (MD) simulation suggest a strong binding of EGCG with TDP-43's aggregation-prone C-terminal domain (CTD). Three replicas, each having 800 ns MD simulation of the EGCG-TDP-43-CTD complex, yielded a high negative binding free energy (ΔG) inferring a stable complex formation. Simulation snapshots show that EGCG forms close and long-lasting contacts with TDP-43's Phe-313 and Ala-341 residues, which were previously identified for monomer recruitment in CTD's aggregation. Notably, stable physical interactions between TDP-43 and EGCG were also detected in vitro using TTC staining and isothermal titration calorimetry which revealed a high-affinity binding site of EGCG on TDP-43 (Kd, 7.8 μM; ΔG, -6.9 kcal/mol). Additionally, TDP-43 co-incubated with EGCG was non-cytotoxic when added to HEK293 cells. In summary, EGCG's binding to TDP-43 and blocking of residues important for aggregation can be a possible mechanism of its anti-aggregation effects on TDP-43.}, } @article {pmid39379597, year = {2024}, author = {Fontdevila, L and Povedano, M and Domínguez, R and Boada, J and Serrano, JC and Pamplona, R and Ayala, V and Portero-Otín, M}, title = {Examining the complex Interplay between gut microbiota abundance and short-chain fatty acid production in amyotrophic lateral sclerosis patients shortly after onset of disease.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {23497}, pmid = {39379597}, issn = {2045-2322}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/microbiology/metabolism ; *Gastrointestinal Microbiome ; Male ; *Fatty Acids, Volatile/metabolism ; Female ; Middle Aged ; Aged ; Adult ; Case-Control Studies ; }, abstract = {This study aimed to assess differences in the enteral microbiome of relatively recent-onset amyotrophic lateral sclerosis (ALS) patients (< 6-15 months since symptom onset) compared to healthy individuals, focusing on short-chain fatty acids (SCFAs) as potential mediators of host metabolism. We included 28 volunteers (16 ALS, 12 controls) with informed consent. No significant effect of ALS on alpha diversity (measuring the variety and abundance of species within a single sample, and indicating the health and complexity of the microbiome) was observed, but ALS patients had higher abundances of Fusobacteria and Acidobacteria. ALS subtypes influenced specific species, with increased Fusobacteria and Tenericutes in spinal ALS compared to bulbar ALS. ALS patients showed increased Enterobacter, Clostridium, Veillonella, Dialister, Turicibacter, and Acidaminococcus species and decreased Prevotella, Lactobacillus, and Butyricimonas. Correlations between species varied between ALS patients and healthy individuals and among ALS subtypes. No significant differences in SCFA concentrations were found, but spinal ALS samples showed a trend towards decreased propionate content. Relationships between SCFAs and phyla colonization differed by disease status. This study suggests distinct enteral microbiome characteristics in ALS patients, though the implications are unclear. Further research is needed to determine if these differences are causative or consequential and to explore their potential as diagnostic or therapeutic targets. The study also underscores the heterogeneity of microbiome constraints in ALS and the need for more research into ALS and SCFA metabolism.}, } @article {pmid39378795, year = {2024}, author = {Lehto, A and Schumacher, J and Kasper, E and Teipel, S and Hermann, A and Prudlo, J}, title = {Loss of the ipsilateral silent period in amyotrophic lateral sclerosis is associated with reduced white matter integrity in the motor section of the corpus callosum.}, journal = {Journal of the neurological sciences}, volume = {466}, number = {}, pages = {123267}, doi = {10.1016/j.jns.2024.123267}, pmid = {39378795}, issn = {1878-5883}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnostic imaging/pathology/psychology ; *Corpus Callosum/diagnostic imaging/pathology ; Male ; Female ; Middle Aged ; *White Matter/diagnostic imaging/pathology ; *Transcranial Magnetic Stimulation/methods ; Aged ; *Motor Cortex/diagnostic imaging/pathology/physiopathology ; Diffusion Tensor Imaging ; Functional Laterality/physiology ; Diffusion Magnetic Resonance Imaging/methods ; Adult ; Neural Inhibition/physiology ; Evoked Potentials, Motor/physiology ; }, abstract = {OBJECTIVE: Interhemispheric neurons in the motor section of the corpus callosum have an inhibitory effect on neurons of the contralateral motor cortex. Three quarters of patients with amyotrophic laterals sclerosis (ALS) show impaired transcallosal inhibition. We aimed to investigate whether structural changes co-occur with this functional impairment and to explore its phenotypic correlates.

METHODS: The demographic, clinical, and neuropsychological data of 127 ALS patients were analysed. Transcallosal inhibition was assessed with an ipsilateral silent period (iSP) protocol using transcranial magnetic stimulation. Patients were categorised based on an iSP response or its loss, and the groups were characterised by demographic, clinical, and neuropsychological variables. Diffusion-weighted images from a subset of 63 patients were analysed using tractography, and white matter (WM) structural integrity metrics were compared across groups.

RESULTS: 54 % of patients displayed iSP loss. The average free-water-corrected fractional anisotropy values within the callosal tract between the primary motor cortices were lower for patients with iSP loss compared to patients with an iSP response. There were no group differences based on other diffusivity metrics. The groups did not differ regarding any of the demographic, clinical, or neuropsychological variables.

INTERPRETATION: We found reduced WM integrity in the motor section of the corpus callosum that differentiated ALS patients with iSP loss from patients with an iSP response, but with a small effect size. Nevertheless, the underlying pathological substrate and potential genetic drivers for these structural and functional changes in a subset of ALS patients remain to be satisfactorily investigated.}, } @article {pmid39378530, year = {2025}, author = {Meng, T and Wu, W and Wang, B and Li, C and Li, J and Liu, J and Wang, J and Qie, R}, title = {Treating chronic pulmonary heart disease with traditional Chinese medicine: Systematic evaluation and mechanistic insights into the resolving phlegm and activating blood approach.}, journal = {Heart & lung : the journal of critical care}, volume = {69}, number = {}, pages = {111-126}, doi = {10.1016/j.hrtlng.2024.09.017}, pmid = {39378530}, issn = {1527-3288}, mesh = {Humans ; Chronic Disease ; *Drugs, Chinese Herbal/therapeutic use/pharmacology ; *Medicine, Chinese Traditional/methods ; *Pulmonary Heart Disease/drug therapy ; Randomized Controlled Trials as Topic ; }, abstract = {BACKGROUND: Chronic Pulmonary Heart Disease (CPHD) significantly impacts global health, especially among middle-aged and older adults. In China, the Traditional Chinese Medicine (TCM) technique of Resolving Phlegm and Activating Blood (RPAB) is widely used to treat CPHD, although high-quality evidence supporting its efficacy remains limited.

OBJECTIVES: The purpose of this study was to rigorously assess the clinical efficacy of RPAB for CPHD and elucidate the mechanisms underlying its primary herbal components.

METHODS: Through a detailed search of literature in both Chinese and English and strict inclusion and exclusion criteria, 18 randomized controlled trials (RCTs) were selected for meta-analysis. We identified RPAB's core herbal combinations using association rule analysis. This method statistically analyzes the frequency and correlation of herbal medicine usage. We then analyzed the chemical components of these combinations and investigated their potential intervention mechanisms on CPHD through network pharmacology.

RESULTS: The combination of RPAB with Western medicine was superior to Western medicine alone in improving blood gas analysis and pulmonary function and reducing plasma viscosity in CPHD patients. The core herbal combination identified was Astragalus membranaceus (Fisch.) Bunge, Ligusticum chuanxiong Hort. ex S. H. Qiu & al., and Stellaria alsine Grimm (ALS). This combination targeted 588 therapeutic and 27 core targets. It influenced ten core compounds across 34 pathways, primarily through the chemokine signaling pathway and the JAK-STAT signaling pathway.

CONCLUSION: RPAB with Western medicine significantly improves CPHD treatment outcomes. The study highlights the therapeutic potential of the ALS combination, which operates through multiple pathways to remodel pulmonary arteries, decrease inflammation, and lessen oxidative stress. These insights support the clinical application of RPAB in CPHD treatment and open new avenues for research and therapeutic development.}, } @article {pmid39378421, year = {2024}, author = {Knox, L and Coates, E and Griffiths, A and Ali, Y and Hobson, E and McDermott, C}, title = {Development and Evaluation of the Telehealth in Motor Neuron Disease System: The TIME Study Protocol.}, journal = {JMIR research protocols}, volume = {13}, number = {}, pages = {e57685}, pmid = {39378421}, issn = {1929-0748}, mesh = {*Motor Neuron Disease/therapy ; Humans ; *Telemedicine ; Surveys and Questionnaires ; Caregivers/psychology ; }, abstract = {BACKGROUND: For more responsive care provision for motor neuron disease and caregivers, a digital system called Telehealth in MND-Care (TiM-C) was created. TiM-C sends regular symptom questionnaires to users; their responses are sent to health care professionals (HCPs). To enable people with motor neuron disease to participate in research studies more easily, a parallel platform was developed from TiM-C, called Telehealth in MND-Research (TiM-R). TiM-R can advertise studies, collect data, and make them available to MND researchers.

OBJECTIVE: This study has 4 work packages (WPs) to facilitate service approval, codevelop the TiM systems, and evaluate the service. Each WP aims to understand (1) what helps and hinders the approval of the TiM-C system as a National Health Service; (2) what aspects of MND care and research are currently unmet and can be addressed through the TiM-C and TiM-R systems; (3) how TiM-C influences MND care, from the perspective of people with motor neuron disease, their caregivers, and HCPs; and (4) the costs and benefits associated with TiM-C.

METHODS: WP1 will use semistructured interviews with 10-15 people involved in the approval of TiM-C to understand the barriers and facilitators to governance processes. WP2 will use individual and group interviews with 25-35 users (people with motor neuron disease, caregivers, HCPs, MND researchers, and industry) of TiM-C and TiM-R to understand the current unmet needs of these user groups and how TiM services can be developed to meet these needs. WP3 will use a process evaluation involving 5 elements; local context, engagement, user experiences, service impact, and mechanisms of action. A range of methods, including audits, analysis of routine data, questionnaires, interviews, and observations will be used with people with motor neuron disease, caregivers, and HCPs, both those using the system and those who declined the service when invited. WP4 will use data collected through the process evaluation and known costs to conduct a cost-consequence and budget impact analysis to explore the cost-benefit of the TiM-C service. Most data collected will be qualitative, with thematic and framework analysis used to develop themes from transcripts and observations. Descriptive statistics or t tests and chi-square tests will be used to describe and analyze quantitative data.

RESULTS: This study has received ethical approval and has begun recruitment in 1 site. Further, 13 specialist MND centers will adopt TiM-C and the TIME study, beginning in July 2024. The study will conclude in November 2026 and a final report will be produced 3 months after the completion date.

CONCLUSIONS: This study will facilitate the implementation and development of TiM-C and TiM-R and fully evaluate the TiM-C service, enabling informed decision-making among health care providers regarding continued involvement and contribute to the wider literature relating to how technology-enabled care services can affect clinical care.

DERR1-10.2196/57685.}, } @article {pmid39377567, year = {2025}, author = {Rani, P and Rajak, BK and Mahato, GK and Rathore, RS and Chandra, G and Singh, DV}, title = {Strategic lead compound design and development utilizing computer-aided drug discovery (CADD) to address herbicide-resistant Phalaris minor in wheat fields.}, journal = {Pest management science}, volume = {81}, number = {5}, pages = {2469-2479}, doi = {10.1002/ps.8455}, pmid = {39377567}, issn = {1526-4998}, support = {//Science and Engineering Research Board, India/ ; //Department of Biotechnology, Ministry of Science and Technology, India/ ; //Department of Science and Technology, Ministry of Science and Technology, India/ ; }, mesh = {*Herbicide Resistance ; *Herbicides/pharmacology/chemistry ; *Triticum/growth & development ; *Drug Discovery/methods ; *Weed Control/methods ; *Phalaris/drug effects ; *Drug Design ; Plant Weeds/drug effects ; Computer-Aided Design ; Molecular Docking Simulation ; }, abstract = {Wheat (Triticum aestivum) is a vital cereal crop and a staple food source worldwide. However, wheat grain productivity has significantly declined as a consequence of infestations by Phalaris minor. Traditional weed control methods have proven inadequate owing to the physiological similarities between P. minor and wheat during early growth stages. Consequently, farmers have turned to herbicides, targeting acetyl-CoA carboxylase (ACCase), acetolactate synthase (ALS) and photosystem II (PSII). Isoproturon targeting PSII was introduced in mid-1970s, to manage P. minor infestations. Despite their effectiveness, the repetitive use of these herbicides has led to the development of herbicide-resistant P. minor biotypes, posing a significant challenge to wheat productivity. To address this issue, there is a pressing need for innovative weed management strategies and the discovery of novel herbicide molecules. The integration of computer-aided drug discovery (CADD) techniques has emerged as a promising approach in herbicide research, that facilitates the identification of herbicide targets and enables the screening of large chemical libraries for potential herbicide-like molecules. By employing techniques such as homology modelling, molecular docking, molecular dynamics simulation and pharmacophore modelling, CADD has become a rapid and cost-effective medium to accelerate the herbicide discovery process significantly. This approach not only reduces the dependency on traditional experimental methods, but also enhances the precision and efficacy of herbicide development. This article underscores the critical role of bioinformatics and CADD in developing next-generation herbicides, offering new hope for sustainable weed management and improved wheat cultivation practices. © 2024 Society of Chemical Industry.}, } @article {pmid39376539, year = {2024}, author = {Kouchmeshky, A and Whiting, A and McCaffery, P}, title = {Neuroprotective effects of ellorarxine in neuronal models of degeneration.}, journal = {Frontiers in neuroscience}, volume = {18}, number = {}, pages = {1422294}, pmid = {39376539}, issn = {1662-4548}, abstract = {INTRODUCTION: Retinoic acid (RA) was first recognised to be important for the central nervous system (CNS) in its developmental regulatory role and, given this action, it has been proposed in the adult CNS to regulate plasticity and promote regeneration. These types of roles have included support of neurogenesis, induction of neurite outgrowth, and protection from neuronal death. These functions are predominantly mediated by the retinoic acid receptor (RAR) transcription factor, and hence agonists for the RARs have been tested in a variety of models of neurodegeneration. This present study employs several in vitro models less explored for the action of RAR agonists to reverse neurodegeneration.

METHODS: A series of assays are used in which neuronal cells are placed under the types of stress that have been linked to neurodegeneration, in particular amyotrophic lateral sclerosis (ALS), and the neuroprotective influence of a new potent agonist for RAR, ellorarxine, is tested out. In these assays, neuronal cells were subjected to excitotoxic stress induced by glutamate, proteostasis disruption caused by epoxomicin, and oxidative stress leading to stress granule formation triggered by sodium arsenite.

RESULTS: Ellorarxine effectively reversed neuronal death in excitotoxic and proteostasis disruption assays and mitigated stress granule formation induced by sodium arsenite. This study also highlights for the first time the novel observation of RAR modulation of stress granules, although it is unknown whether this change in stress granules will be neuroprotective or potentially regenerative. Furthermore, the distribution of RAR agonists following intraperitoneal injection was assessed in mice, revealing preferential accumulation in the central nervous system, particularly in the spinal cord, compared to the liver. Gene expression studies in the spinal cord demonstrated that ellorarxine induces transcriptional changes at a low dose (0.01 mg/kg).

DISCUSSION: These findings underscore the therapeutic potential of RAR agonists, such as ellorarxine, for ALS and potentially other neurodegenerative diseases.}, } @article {pmid39376212, year = {2024}, author = {Tomiyama, ALMR and Cartarozzi, LP and de Oliveira Coser, L and Chiarotto, GB and Oliveira, ALR}, title = {Corrigendum: Neuroprotection by upregulation of the major histocompatibility complex class I (MHC I) in SOD1[G93A] mice.}, journal = {Frontiers in cellular neuroscience}, volume = {18}, number = {}, pages = {1493884}, doi = {10.3389/fncel.2024.1493884}, pmid = {39376212}, issn = {1662-5102}, abstract = {[This corrects the article DOI: 10.3389/fncel.2023.1211486.].}, } @article {pmid39375835, year = {2024}, author = {Altomare, D and Bracca, V and Premi, E and Micheli, A and Cotelli, MS and Gasparotti, R and Alberici, A and Borroni, B}, title = {Clinical and imaging correlates of hyperorality in syndromes associated with frontotemporal lobar degeneration.}, journal = {Psychiatry and clinical neurosciences}, volume = {78}, number = {12}, pages = {818-825}, pmid = {39375835}, issn = {1440-1819}, mesh = {Humans ; Male ; Female ; Aged ; Middle Aged ; *Frontotemporal Lobar Degeneration/diagnostic imaging/pathology/physiopathology ; Retrospective Studies ; *Frontotemporal Dementia/diagnostic imaging/physiopathology/pathology ; Longitudinal Studies ; Magnetic Resonance Imaging ; Amyotrophic Lateral Sclerosis/diagnostic imaging/complications ; }, abstract = {AIM: Empirical research investigating hyperorality in syndromes associated with frontotemporal lobar degeneration (FTLD) is limited. The present study aims to assess and describe hyperorality and its clinical and imaging correlates in patients with FTLD-associated syndromes.

METHODS: This retrospective longitudinal study included consecutive patients with FTLD who underwent a clinical, cognitive, and behavioral assessment. The presence and severity of hyperorality was assessed using the Frontal Behavior Inventory.

RESULTS: A total of 712 patients with FTLD were included in the study. Hyperorality was reported by 29% (204 of 712 [95% CI: 25-32%]) of patients; was more frequent in those with severe dementia than in those with prodromal or mild to moderate dementia (P < 0.05); was associated with younger age (odds ratio [OR] = 0.96 [95% CI: 0.94-0.99]), (P = 0.003) and positive family history for dementia (OR = 2.03 [95% CI: 1.18-3.49], P = 0.010); was overall more probable in the behavioral variant of frontotemporal dementia (bvFTD) and frontotemporal dementia with amyotrophic lateral sclerosis phenotypes, and less probable in other language or motor phenotypes; and was associated with higher severity of neuropsychiatric symptoms (OR = 1.08 [95% CI: 1.06-1.10], P < 0.001) and with the presence of several behavioral symptoms (P < 0.05). Moreover, hyperorality severity increased over time only in patients with bvFTD (β = +0.15, P = 0.011) or semantic variant of primary progressive aphasia (β = +0.34, P = 0.010). Finally, the presence of hyperorality was significantly associated with greater atrophy in the right anterior insula and right orbitofrontal region (false discovery rate-corrected P < 0.05).

CONCLUSION: Hyperorality is common in certain FTLD-associated syndromes. Understanding its correlates can help clinicians define pharmacological and educational interventions and clarify related anatomical circuits.}, } @article {pmid39375041, year = {2024}, author = {Shah, NM and Rossel, A and Abdulaziz, B and Sheridan, S and Madden-Scott, S and Radcliffe, G and D'Cruz, R and Suh, ES and Steier, J and Hart, N and Murphy, PB and Ramsay, M and Kaltsakas, G}, title = {Effect of nostril occlusion and mouth sealing in the measurement of sniff nasal inspiratory pressure.}, journal = {Thorax}, volume = {80}, number = {1}, pages = {42-44}, doi = {10.1136/thorax-2024-221910}, pmid = {39375041}, issn = {1468-3296}, mesh = {Humans ; Male ; Female ; Middle Aged ; Aged ; *Respiratory Muscles/physiology/physiopathology ; *Amyotrophic Lateral Sclerosis/physiopathology ; *Inhalation/physiology ; *Mouth ; Adult ; Nose ; Muscle Strength/physiology ; Respiratory Function Tests/methods ; }, abstract = {Sniff nasal inspiratory pressure (SNIP) is used to assess respiratory muscle strength in neuromuscular diseases like amyotrophic lateral sclerosis (ALS). The effect of contralateral nostril occlusion and mouth sealing on SNIP measurement are unclear. 81 participants were included (16 healthy, 39 patients with limb-onset ALS and 26 patients with bulbar-onset ALS). SNIP was obtained with combinations of mouth open/sealed and contralateral nostril open/occluded. Occluding the contralateral nostril (with mouth closed) increased SNIP by 12 cmH2O (95% CI 4, 20; p=0.003) in the healthy participants, by 9 cmH2O (95% CI 5, 12; p<0.001) in the limb-onset cohort and by 10 cmH2O (95% CI 5, 14; p<0.001) in the bulbar-onset cohort. Opening the mouth decreased SNIP by 19 cmH2O (95% CI 5, 34; p<0.009) in healthy participants, by 8 cmH2O (95% CI 4, 13; p<0.001) in the limb-onset cohort and by 13 cmH2O (95% CI 7, 19; p<0.001) in the bulbar-onset cohort. With contralateral nostril occlusion, 11% fewer individuals would have qualified for non-invasive ventilation. In conclusion, contralateral nostril occlusion increased SNIP compared with standard technique, likely reflecting true strength. Opening the mouth reduced SNIP, emphasising the need for good mouth sealing. Documenting SNIP technique is important for longitudinal assessments and clinical decision-making.}, } @article {pmid39374890, year = {2024}, author = {Zhang, J and Liu, L and Li, M and Liu, H and Gong, X and Tang, Y and Zhang, Y and Zhou, X and Lin, Z and Guo, H and Pan, L}, title = {Molecular Basis of the Recognition of the Active Rab8a by Optineurin.}, journal = {Journal of molecular biology}, volume = {436}, number = {22}, pages = {168811}, doi = {10.1016/j.jmb.2024.168811}, pmid = {39374890}, issn = {1089-8638}, mesh = {*rab GTP-Binding Proteins/metabolism/chemistry/genetics ; *Cell Cycle Proteins/metabolism/chemistry/genetics ; *Membrane Transport Proteins/metabolism/chemistry/genetics ; Humans ; *Protein Binding ; *Transcription Factor TFIIIA/metabolism/genetics/chemistry ; Models, Molecular ; Amyotrophic Lateral Sclerosis/genetics/metabolism ; Crystallography, X-Ray ; GTPase-Activating Proteins/metabolism/chemistry/genetics ; Mutation ; Protein Conformation ; }, abstract = {Optineurin (OPTN), a multifunctional adaptor protein in mammals, plays critical roles in many cellular processes, such as vesicular trafficking and autophagy. Notably, mutations in optineurin are directly associated with many human diseases, such as amyotrophic lateral sclerosis (ALS). OPTN can specifically recognize Rab8a and the GTPase-activating protein TBC1D17, and facilitate the inactivation of Rab8a mediated by TBC1D17, but with poorly understood mechanism. Here, using biochemical and structural approaches, we systematically characterize the interaction between OPTN and Rab8a, revealing that OPTN selectively recognizes the GTP-bound active Rab8a through its leucine-zipper domain (LZD). The determined crystal structure of OPTN LZD in complex with the active Rab8a not only elucidates the detailed binding mechanism of OPTN with Rab8a but also uncovers a unique binding mode of Rab8a with its effectors. Furthermore, we demonstrate that the central coiled-coil domain of OPTN and the active Rab8a can simultaneously interact with the TBC domain of TBC1D17 to form a ternary complex. Finally, based on the OPTN LZD/Rab8a complex structure and relevant biochemical analyses, we also evaluate several known ALS-associated mutations found in the LZD of OPTN. Collectively, our findings provide mechanistic insights into the interaction of OPTN with Rab8a, expanding our understanding of the binding modes of Rab8a with its effectors and the potential etiology of diseases caused by OPTN mutations.}, } @article {pmid39374680, year = {2024}, author = {Tirassa, P and Rosso, P and Fico, E and Marenco, M and Mallone, F and Gharbiya, M and Lambiase, A and Severini, C}, title = {Perspective role of Substance P in Amyotrophic Lateral Sclerosis: From neuronal vulnerability to neuroprotection.}, journal = {Neuroscience and biobehavioral reviews}, volume = {167}, number = {}, pages = {105914}, doi = {10.1016/j.neubiorev.2024.105914}, pmid = {39374680}, issn = {1873-7528}, mesh = {*Substance P/metabolism ; *Amyotrophic Lateral Sclerosis/metabolism/physiopathology ; Humans ; Animals ; Receptors, Neurokinin-1/metabolism ; Neuroprotection/physiology ; Motor Neurons/metabolism/physiology ; }, abstract = {The neuropeptide Substance P (SP) and its preferred Neurokinin1 Receptor (NK1R) are known to participate in the physiopathology of neurodegenerative diseases and mainly exert a neuroprotective role. In the present work, we have described the involvement of SP and NK1R in Amyotrophic Lateral Sclerosis (ALS). This was demonstrated by the detection of altered levels of SP in the brain, spinal cord and cerebrospinal fluid (CSF) of patients and preclinical models of ALS, and by its ability to inhibit excitotoxicity-induced neurodegeneration in ALS animal models. These data are supported by results indicating an excitatory effect of SP at the motor neuron (MN) level, which promotes locomotor activity. ALS patients are characterized by a differential susceptibility to MNs degeneration, since sphincters and extraocular muscles are classically spared. It is hypothesized that SP may play a role in the maintenance of the ocular system and the innervation of the pelvic floor by contributing directly or indirectly to the selective resistance of this subset of MNs.}, } @article {pmid39373990, year = {2024}, author = {Appel, SH and Thonhoff, JR}, title = {Barriers to Tofersen Therapy for Variant SOD1-Mediated ALS.}, journal = {JAMA neurology}, volume = {81}, number = {12}, pages = {1239-1240}, doi = {10.1001/jamaneurol.2024.3331}, pmid = {39373990}, issn = {2168-6157}, } @article {pmid39373307, year = {2025}, author = {Rajagopalan, V and Pioro, EP}, title = {Graph theory network analysis reveals widespread white matter damage in brains of patients with classic ALS.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {26}, number = {1-2}, pages = {85-92}, doi = {10.1080/21678421.2024.2410281}, pmid = {39373307}, issn = {2167-9223}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnostic imaging/pathology ; Male ; Female ; *White Matter/diagnostic imaging/pathology ; Middle Aged ; Magnetic Resonance Imaging ; *Brain/pathology/diagnostic imaging ; Aged ; Gray Matter/diagnostic imaging/pathology ; Adult ; Image Processing, Computer-Assisted ; *Nerve Net/diagnostic imaging/pathology ; }, abstract = {OBJECTIVE: Amyotrophic lateral sclerosis (ALS) exhibits several different presentations and clinical phenotypes. Of these, classic ALS (ALS-Cl), which is the most common phenotype, presents with relatively equal amounts of upper motor neuron and lower motor neuron signs. Magnetic resonance imaging (MRI) provides a noninvasive way to assess central nervous system damage in these patients. To our knowledge no study is available where exploratory whole brain grey matter (GM) and white matter (WM) network analysis is performed considering only the ALS-Cl subgroup of ALS patients.

METHODS: GM voxel-based morphometry analysis and WM network analysis using graph theory was performed in the MRI dataset of 14 neurologic controls and 25 ALS-Cl patients.

RESULTS AND CONCLUSIONS: No significant GM differences were observed between ALS-Cl and neurologic controls. WM network revealed significant (p < 0.05) reduction and increase in degree measure in several extramotor brain regions of ALS-Cl patients. Both global and local graph metrics revealed significant abnormal values in ALS-Cl patients when compared to neurologic controls. Significant WM changes in ALS-Cl patients with no significant GM changes suggest that neurodegeneration may onset as an "axonopathy" in this ALS subtype.}, } @article {pmid39372031, year = {2024}, author = {Pillai, M and Jha, SK}, title = {Conformational Enigma of TDP-43 Misfolding in Neurodegenerative Disorders.}, journal = {ACS omega}, volume = {9}, number = {39}, pages = {40286-40297}, pmid = {39372031}, issn = {2470-1343}, abstract = {Misfolding and aggregation of the protein remain some of the most common phenomena observed in neurodegeneration. While there exist multiple neurodegenerative disorders characterized by accumulation of distinct proteins, what remains particularly interesting is the ability of these proteins to undergo a conformational change to form aggregates. TDP-43 is one such nucleic acid binding protein whose misfolding is associated with many neurogenerative diseases including amyotrophic lateral sclerosis (ALS) and fronto-temporal lobar degeneration (FTLD). TDP-43 protein assumes several different conformations and oligomeric states under the diseased condition. In this review, we explore the intrinsic relationship between the conformational variability of TDP-43 protein, with a particular focus on the RRM domains, and its propensity to undergo aggregation. We further emphasize the probable mechanism behind the formation of these conformations and suggest a potential diagnostic and therapeutic strategy in the context of these conformational states of the protein.}, } @article {pmid39371851, year = {2024}, author = {Po, K and Olaivar, M}, title = {Juvenile Amyotrophic Lateral Sclerosis: A Case Report of a Rare and Aggressive Presentation in a 22-Year-Old Filipino Male.}, journal = {Cureus}, volume = {16}, number = {9}, pages = {e68579}, pmid = {39371851}, issn = {2168-8184}, abstract = {Amyotrophic Lateral Sclerosis (ALS) is a rare neurodegenerative disorder primarily affecting adults, but juvenile-onset ALS is exceptionally rare. We report a rare case of a 22-year-old Filipino male patient who exhibited early-onset weakness, muscle atrophy, and tongue fasciculations, followed by rapidly progressive dysphagia and respiratory distress. Electromyography - Nerve Conduction Velocity (EMG-NCV) findings showed evidence for a chronic, active predominantly motor neuronal-axonal loss type of neuropathy involving the tongue and limb muscles bilaterally consistent with a motor neuron disease. The patient was treated with riluzole with no significant improvement in symptoms. Despite multidisciplinary interventions, the disease rapidly progressed, highlighting the challenges in managing juvenile ALS cases. This case report emphasizes the importance of considering ALS in the differential diagnosis of progressive motor dysfunction in younger patients and the complexities involved in their care.}, } @article {pmid39371161, year = {2024}, author = {Angrick, M and Luo, S and Rabbani, Q and Joshi, S and Candrea, DN and Milsap, GW and Gordon, CR and Rosenblatt, K and Clawson, L and Maragakis, N and Tenore, FV and Fifer, MS and Ramsey, NF and Crone, NE}, title = {Real-time detection of spoken speech from unlabeled ECoG signals: A pilot study with an ALS participant.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, pmid = {39371161}, support = {UH3 NS114439/NS/NINDS NIH HHS/United States ; }, abstract = {OBJECTIVE: Brain-Computer Interfaces (BCIs) hold significant promise for restoring communication in individuals with partial or complete loss of the ability to speak due to paralysis from amyotrophic lateral sclerosis (ALS), brainstem stroke, and other neurological disorders. Many of the approaches to speech decoding reported in the BCI literature have required time-aligned target representations to allow successful training - a major challenge when translating such approaches to people who have already lost their voice.

APPROACH: In this pilot study, we made a first step toward scenarios in which no ground truth is available. We utilized a graph-based clustering approach to identify temporal segments of speech production from electrocorticographic (ECoG) signals alone. We then used the estimated speech segments to train a voice activity detection (VAD) model using only ECoG signals. We evaluated our approach using held-out open-loop recordings of a single dysarthric clinical trial participant living with ALS, and we compared the resulting performance to previous solutions trained with ground truth acoustic voice recordings.

MAIN RESULTS: Our approach achieves a median error rate of around 0.5 seconds with respect to the actual spoken speech. Embedded into a real-time BCI, our approach is capable of providing VAD results with a latency of only 10 ms.

SIGNIFICANCE: To the best of our knowledge, our results show for the first time that speech activity can be predicted purely from unlabeled ECoG signals, a crucial step toward individuals who cannot provide this information anymore due to their neurological condition, such as patients with locked-in syndrome.

CLINICAL TRIAL INFORMATION: ClinicalTrials.gov, registration number NCT03567213.}, } @article {pmid39370211, year = {2024}, author = {Kajitani, GS and Xavier, G and Villena-Rueda, BE and Karia, BTR and Santoro, ML}, title = {Extracellular vesicles in neurodegenerative, mental, and other neurological disorders: Perspectives into mechanisms, biomarker potential, and therapeutic implications.}, journal = {Current topics in membranes}, volume = {94}, number = {}, pages = {299-336}, doi = {10.1016/bs.ctm.2024.06.002}, pmid = {39370211}, issn = {1063-5823}, mesh = {Humans ; *Extracellular Vesicles/metabolism ; *Neurodegenerative Diseases/metabolism/pathology/therapy ; *Biomarkers/metabolism ; Mental Disorders/metabolism/drug therapy/therapy ; Animals ; Nervous System Diseases/metabolism/pathology ; }, abstract = {Extracellular vesicles (EVs) are produced, secreted, and targeted by most human cells, including cells that compose nervous system tissues. EVs carry several types of biomolecules, such as lipids, proteins and microRNA, and can function as signaling agents in physiological and pathological processes. In this chapter, we will focus on EVs and their cargo secreted by brain cells, especially neurons and glia, and how these aspects are affected in pathological conditions. The chapter covers neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis, as well as several psychiatric disorders, namely schizophrenia, autism spectrum disorder and major depressive disorder. This chapter also addresses other types of neurological dysfunctions, epilepsy and traumatic brain injury. EVs can cross the blood brain barrier, and thus brain EVs may be detected in more accessible peripheral tissue, such as circulating blood. Alterations in EV composition and contents can therefore impart valuable clues into the molecular etiology of these disorders, and serve biomarkers regarding disease prevalence, progression and treatment. EVs can also be used to carry drugs and biomolecules into brain tissue, considered as a promising drug delivery agent for neurological diseases. Therefore, although this area of research is still in its early development, it offers great potential in further elucidating and in treating neurological disorders.}, } @article {pmid39369804, year = {2024}, author = {Daniels, N and Bindoff, AD and Vickers, JC and King, AE and Collins, JM}, title = {Vulnerability of neurofilament-expressing neurons in frontotemporal dementia.}, journal = {Molecular and cellular neurosciences}, volume = {131}, number = {}, pages = {103974}, doi = {10.1016/j.mcn.2024.103974}, pmid = {39369804}, issn = {1095-9327}, mesh = {Humans ; *Frontotemporal Dementia/metabolism/genetics/pathology ; Aged ; *Neurons/metabolism/pathology ; *Neurofilament Proteins/metabolism ; Female ; Male ; Middle Aged ; *tau Proteins/metabolism/genetics ; Aged, 80 and over ; DNA-Binding Proteins/metabolism/genetics ; }, abstract = {Frontotemporal dementia (FTD) is an umbrella term for several early onset dementias, that are caused by frontotemporal lobar degeneration (FTLD), which involves the atrophy of the frontal and temporal lobes of the brain. Neuron loss in the frontal and temporal lobes is a characteristic feature of FTLD, however the selective vulnerability of different neuronal populations in this group of diseases is not fully understood. Neurofilament-expressing neurons have been shown to be selectively vulnerable in other neurodegenerative diseases, including Alzheimer's disease and amyotrophic lateral sclerosis, therefore we sought to investigate whether this neuronal population is vulnerable in FTLD. We also examined whether neuronal sub-type vulnerability differed between FTLD with TDP-43 inclusions (FTLD-TDP) and FTLD with tau inclusions (FTLD-Tau). Post-mortem human tissue from the superior frontal gyrus (SFG) of FTLD-TDP (n = 15), FTLD-Tau (n = 8) and aged Control cases (n = 6) was immunolabelled using antibodies against non-phosphorylated neurofilaments (SMI32 antibody), calretinin and NeuN, to explore neuronal cell loss. The presence of non-phosphorylated neurofilament immunolabelling in axons of the SFG white matter was also quantified as a measure of axon pathology, as axonal neurofilaments are normally phosphorylated. We demonstrate the selective loss of neurofilament-expressing neurons in both FTLD-TDP and FTLD-Tau cases compared to aged Controls. We also show that non-phosphorylated neurofilament axonal pathology in the SFG white matter was associated with increasing age, but not FTLD. This data suggests neurofilament-expressing neurons are vulnerable in both FTLD-TDP and FTLD-Tau.}, } @article {pmid39369616, year = {2024}, author = {Zhao, Y and Li, X and Wang, K and Iyer, G and Sakowski, SA and Zhao, L and Teener, S and Bakulski, KM and Dou, JF and Traynor, BJ and Karnovsky, A and Batterman, SA and Feldman, EL and Sartor, MA and Goutman, SA}, title = {Epigenetic age acceleration is associated with occupational exposures, sex, and survival in amyotrophic lateral sclerosis.}, journal = {EBioMedicine}, volume = {109}, number = {}, pages = {105383}, pmid = {39369616}, issn = {2352-3964}, support = {R01 TS000289/TS/ATSDR CDC HHS/United States ; R01 TS000327/TS/ATSDR CDC HHS/United States ; K23 ES027221/ES/NIEHS NIH HHS/United States ; R01 ES030049/ES/NIEHS NIH HHS/United States ; P30 ES017885/ES/NIEHS NIH HHS/United States ; UL1 TR002240/TR/NCATS NIH HHS/United States ; R01 NS120926/NS/NINDS NIH HHS/United States ; R01 NS127188/NS/NINDS NIH HHS/United States ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/etiology/mortality ; Male ; Female ; *Epigenesis, Genetic ; *Occupational Exposure/adverse effects ; Middle Aged ; *DNA Methylation ; Aged ; Sex Factors ; Aging/genetics ; Case-Control Studies ; Adult ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is linked to ageing and genetic and environmental risk factors, yet underlying mechanisms are incompletely understood. We aimed to evaluate epigenetic age acceleration (EAA), i.e., DNA methylation (DNAm) age acceleration, and its association with ALS case status and survival.

METHODS: In this study, we included 428 ALS and 288 control samples collected between 2011 and 2021. We calculated EAA using the GrimAge residual method from ALS and control blood samples and grouped participants with ALS into three ageing groups (fast, normal, slow). We associated EAA with ALS case status and survival, stratified by sex, and correlated it with environmental and biological factors through occupational exposure assessments, immune cell proportions, and transcriptome changes.

FINDINGS: Participants with ALS had higher average EAA by 1.80 ± 0.30 years (p < 0.0001) versus controls. Participants with ALS in the fast ageing group had a hazard ratio of 1.52 (95% confidence interval 1.16-2.00, p = 0.0028) referenced to the normal ageing group. In males, this hazard ratio was 1.55 (95% confidence interval 1.11-2.17, p = 0.010), and EAA was positively correlated with high-risk occupational exposures including particulate matter (adj.p < 0.0001) and metals (adj.p = 0.0087). Also, in male participants with ALS, EAA was positively correlated with neutrophil proportions and was negatively correlated with CD4+ T cell proportions. Pathways dysregulated in participants with ALS with fast ageing included spliceosome, nucleocytoplasmic transport, axon guidance, and interferons.

INTERPRETATION: EAA was associated with ALS case status and, at least in males, with shorter survival after diagnosis. The effect of EAA on ALS was partially explained by occupational exposures and immune cell proportions in a sex-dependent manner. These findings highlight the complex interactions of ageing and exposures in ALS.

FUNDING: NIH, CDC/National ALS Registry, ALS Association, Dr. Randall Whitcomb Fund for ALS Genetics, Peter Clark Fund for ALS Research, Sinai Medical Staff Foundation, Scott L. Pranger ALS Clinic Fund, NeuroNetwork Therapeutic Discovery Fund, NeuroNetwork for Emerging Therapies.}, } @article {pmid39368746, year = {2024}, author = {Sharma, R and Mehan, S and Khan, Z and Das Gupta, G and Narula, AS}, title = {Therapeutic potential of oleanolic acid in modulation of PI3K/Akt/mTOR/STAT-3/GSK-3β signaling pathways and neuroprotection against methylmercury-induced neurodegeneration.}, journal = {Neurochemistry international}, volume = {180}, number = {}, pages = {105876}, doi = {10.1016/j.neuint.2024.105876}, pmid = {39368746}, issn = {1872-9754}, mesh = {Animals ; *Oleanolic Acid/pharmacology/therapeutic use ; Rats ; *Neuroprotective Agents/pharmacology/therapeutic use ; *Signal Transduction/drug effects ; Male ; *Methylmercury Compounds/toxicity ; *Glycogen Synthase Kinase 3 beta/metabolism ; *TOR Serine-Threonine Kinases/metabolism ; *Proto-Oncogene Proteins c-akt/metabolism ; *Phosphatidylinositol 3-Kinases/metabolism ; Rats, Wistar ; Amyotrophic Lateral Sclerosis/drug therapy/metabolism ; Neuroprotection/drug effects ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder that gradually deteriorates motor neurons, leading to demyelination, muscle weakness, and eventually respiratory failure. The disease involves several pathological processes, such as increased glutamate levels, mitochondrial dysfunction, and persistent neuroinflammation, often exacerbated by environmental toxins like mercury. This study explores the therapeutic potential of Olea europaea active phytoconstituents oleanolic acid (OLA) against ALS by targeting the overactivated PI3K/Akt/mTOR/STAT-3/GSK-3β signalling pathways. Methods involved in-silico studies, in vitro and in vivo experiments in which varying doses of methylmercury 5 mg/kg, p.o. and OLA (100 and 200 mg/kg, i.p.) were administered to rats for 42 days. Behavioural assessments, gross morphological, histopathological, and neurochemical parameters were measured in cerebrospinal fluid (CSF), blood plasma, and brain homogenates (cerebral cortex, hippocampus, striatum, midbrain, cerebellum) along with complete blood count (CBC) analysis. Results revealed OLA's significant neuroprotective properties. OLA effectively modulated targeted pathways, reducing pro-inflammatory cytokines, restoring normal levels of myelin basic protein (MBP) and neurofilament light chain (NEFL), and reducing histopathological changes. Gross pathological studies indicated less tissue damage, while CBC analysis showed improved hematology parameters. Additionally, the combination of OLA and edaravone (10 mg/kg, i.p.) demonstrated enhanced efficacy, improving motor functions and extending survival in ALS model rats. In conclusion, OLA exhibits significant therapeutic potential for ALS, acting as a potent modulator of key pathological signaling pathways. The findings suggest the feasibility of integrating OLA into existing treatment regimens, potentially improving clinical outcomes for ALS patients. However, further research must validate these findings in human clinical trials.}, } @article {pmid39368179, year = {2025}, author = {Brito, ALB and Cardoso, IF and Viegas, LP and Fausto, R}, title = {Semi-quantitative chemometric models for characterization of mixtures of sugars using infrared spectral data.}, journal = {Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy}, volume = {326}, number = {}, pages = {125225}, doi = {10.1016/j.saa.2024.125225}, pmid = {39368179}, issn = {1873-3557}, mesh = {*Chemometrics/methods ; *Models, Chemical ; *Sugars/analysis ; Spectrophotometry, Infrared ; Principal Component Analysis ; Multivariate Analysis ; Least-Squares Analysis ; }, abstract = {Sugars (saccharides) are sweet-tasting carbohydrates that are abundant in foods and play very important roles in living organisms, particularly as sources and stores of energy, and as structural elements in cellular membranes. They are desirable therapeutic targets, as they participate in multiple metabolic processes as fundamental elements. However, the physicochemical characterization of sugars is a challenging task, mostly due to the structural similarity shared by the large diversity of compounds of this family. The need for fast, accurate enough, and cost-effective analytical methods for these substances is of extreme relevance, in particular because of the recently increasing importance of carbohydrates in Medicine and food industry. With this in view, this work focused on the development of chemometric models for semi-quantitative analysis of samples of different types of sugars (glucose, galactose, mannitol, sorbose and fructose) using infrared spectra as data, as an example of application of a novel approach, where the Principal Component Analysis (PCA) score plots are used to estimate the composition (weight-%) of the mixtures of the sugars. In these plots, polygonal geometric shapes emerge in the vectorial space of the most significant principal components, that allow grouping different types of samples on the vertices, edges, faces and interior of the polygons according to the composition of the samples. This approach was applied successfully to mixtures of up to 5 sugars and shown to appropriately extract the compositional information from the hyper-redundant complex spectral data. Thought the method has been applied here to a specific problem, it shall be considered as a general procedure for the semi-quantitative analysis of other types of mixtures and applicable to other types of data reflecting their composition. In fact, the methodology appears as an efficient tool to solve three main general problems: (i) use hyper-redundant (in variables) data, as spectral information, directly and with minimum pre-treatment, to evaluate semi-quantitatively the composition of mixtures; (ii) do this for systems which produce data that can be considered rather similar; and (iii) do it for a number of substances present in the mixtures that might be greater than that usually considered in chemistry, which in general is limited to 3 components. In addition, this work also demonstrates that, similarly to the developed analysis based on the PCA score plots, the Multivariate Curve Resolution with Alternating Least Squares (MCR-ALS) chemometric method can also be used successfully for the qualitative (when used without any previous knowledge of the components present in the samples) or semi-quantitative (when the pure components spectral profiles are provided as references) analyses of mixtures of (at least) up to 5 distinct sugars.}, } @article {pmid39367779, year = {2025}, author = {Duran, S and Aydogdu, A}, title = {The effect of structured psychoeducation for caregivers of ALS patients on perceived stress, psychological resilience and self-compassion.}, journal = {Health education research}, volume = {40}, number = {1}, pages = {}, doi = {10.1093/her/cyae031}, pmid = {39367779}, issn = {1465-3648}, mesh = {Humans ; *Caregivers/psychology/education ; Male ; Female ; *Amyotrophic Lateral Sclerosis/psychology ; *Resilience, Psychological ; Middle Aged ; *Empathy ; *Stress, Psychological/prevention & control/psychology ; Adaptation, Psychological ; Adult ; Aged ; Turkey ; Surveys and Questionnaires ; }, abstract = {Patients diagnosed with amyotrophic lateral sclerosis (ALS) become dependent on caregivers to meet their daily needs and perform personal care activities. For this reason, ALS is a disease that can challenge both the patient and the caregiver physically, mentally and socially. Supporting the caregiver indirectly affects the patient's quality of care and mental well-being. Therefore, this study aimed to determine the effect of a structured psychoeducation program on coping with stress, psychological resilience and self-compassion in caregivers of ALS patients. This quasi-experimental study with a pre-test-post-test control group was conducted with caregivers of 62 ALS patients in Türkiye. The study was conducted between July 2023 and February 2024. A psychoeducation program was applied to five different groups via zoom application for 6 weeks each. The survey form, Perceived Stress Scale, Brief Resilience Scale and Short Form of Self-Compassion Questionnaire were used as measurement tools. The chi-squared test and paired samples t-test were used to analyze the data. While there was no significant difference between the intervention group and the control group in the pre-test in terms of their mean scores on the coping with stress inventory, short psychological resilience scale and self-compassion scale, at the post-test, psychological resilience and self-compassion scores were significantly higher in the intervention group. This study revealed that psychoeducational programs that support caregivers are effective in increasing psychological resilience and self-compassion.}, } @article {pmid39367309, year = {2024}, author = {Makled, AF and Ali, SAM and Labeeb, AZ and Salman, SS and Shebl, DZM and Hegazy, SG and Sabal, MS}, title = {Characterization of Candida species isolated from clinical specimens: insights into virulence traits, antifungal resistance and molecular profiles.}, journal = {BMC microbiology}, volume = {24}, number = {1}, pages = {388}, pmid = {39367309}, issn = {1471-2180}, mesh = {Humans ; *Candida/genetics/pathogenicity/drug effects/isolation & purification/classification ; *Drug Resistance, Fungal/genetics ; *Antifungal Agents/pharmacology ; *Virulence Factors/genetics ; *Candidiasis/microbiology ; *Biofilms/growth & development ; *Microbial Sensitivity Tests ; Virulence/genetics ; Multiplex Polymerase Chain Reaction ; Male ; Female ; Adult ; Middle Aged ; Young Adult ; Adolescent ; }, abstract = {BACKGROUND: Candida species have emerged as a significant cause of opportunistic infections. Alongside the expression of various virulence factors, the rise of antifungal resistance among Candida species presents a considerable clinical challenge.

AIM: This study aimed to identify different Candida species isolated from clinical specimens, evaluate their antifungal sensitivity patterns, identify key genes regulating virulence mechanisms using multiplex PCR and to assess any correlation between their virulence profiles and antifungal resistance patterns.

METHOD: A total of 100 Candida spp. was isolated from 630 different clinical specimens and identified to the species level. Their antifungal susceptibility was phenotypically evaluated in accordance with CLSI guidelines using the Vitek-2 Compact System. Virulence markers, including biofilm formation capacity, protease production, melanin production, coagulase production and hemolysin production, were also phenotypically detected. The genetic determinants for biofilm formation and extracellular hydrolytic enzymes were assessed using a multiplex PCR assay.

RESULTS: The prevalence of Candida spp. was 15.9%, with C. albicans (48%) and C. glabrata (16%) being the most common. C. albicans showed the highest virulence, with strong biofilm formation, and high proteinase and melanin production. Multiplex PCR revealed Hlp in 22.0%, Hwp in 80.0%, Als in 56.0%, and Sap genes in 56.0% of isolates. Virulence genes were more common in C. albicans than in non-albicans Candida (NAC). Resistance patterns significantly correlated with virulence profiles, with notable associations between flucytosine resistance and the presence of Hlp and Hwp genes.

CONCLUSION: The significant correlation between virulent markers such as germination, coagulase, hemolysin production and resistance patterns among different Candida isolates is crucial for predicting the severity and outcomes of Candida infections. This understanding aids in guiding tailored treatment strategies.}, } @article {pmid39367212, year = {2024}, author = {Cogan, G and Zaki, MS and Issa, M and Keren, B and Guillaud-Bataille, M and Renaldo, F and Isapof, A and Lallemant, P and Stevanin, G and Guillot-Noel, L and Courtin, T and Buratti, J and Freihuber, C and Gleeson, JG and Howarth, R and Durr, A and de Sainte Agathe, JM and Mignot, C}, title = {Biallelic variants in ERLIN1: a series of 13 individuals with spastic paraparesis.}, journal = {Human genetics}, volume = {143}, number = {11}, pages = {1353-1362}, pmid = {39367212}, issn = {1432-1203}, mesh = {Humans ; Female ; Male ; *Paraparesis, Spastic/genetics ; *Pedigree ; Child ; Adolescent ; Adult ; Membrane Proteins/genetics ; Alleles ; Phenotype ; Mutation ; Child, Preschool ; Young Adult ; Intellectual Disability/genetics ; }, abstract = {Biallelic variants in the ERLIN1 gene were recently reported as the cause of two motor neuron degeneration diseases, SPG62 and a recessive form of amyotrophic lateral sclerosis. However, only 12 individuals from five pedigrees have been identified so far. Thus, the description of the disease remains limited. Following the discovery of a homozygous pathogenic variant in a girl with SPG62, presenting with intellectual disability, and epilepsy, we gathered the largest series of SPG62 cases reported so far (13 individuals) to better understand the phenotype associated with ERLIN1. We collected molecular and clinical data for 13 individuals from six families with ERLIN1 biallelic variants. We performed RNA-seq analyses to characterize intronic variants and used Alphafold and a transcripts database to characterize the molecular consequences of the variants. We identified three new variants suspected to alter the bell-shaped ring formed by the ERLIN1/ERLIN2 complex. Affected individuals had childhood-onset paraparesis with slow progression. Six individuals presented with gait ataxia and three had superficial sensory loss. Aside from our proband, none had intellectual disability or epilepsy. Biallelic pathogenic ERLIN1 variants induce a rare, predominantly pure, spastic paraparesis, with possible cerebellar and peripheral nerve involvement.}, } @article {pmid39367160, year = {2024}, author = {Metzger, M and Dukic, S and McMackin, R and Giglia, E and Mitchell, M and Bista, S and Costello, E and Peelo, C and Tadjine, Y and Sirenko, V and McManus, L and Buxo, T and Fasano, A and Chipika, R and Pinto-Grau, M and Schuster, C and Heverin, M and Coffey, A and Broderick, M and Iyer, PM and Mohr, K and Gavin, B and Pender, N and Bede, P and Muthuraman, M and Hardiman, O and Nasseroleslami, B}, title = {Distinct Longitudinal Changes in EEG Measures Reflecting Functional Network Disruption in ALS Cognitive Phenotypes.}, journal = {Brain topography}, volume = {38}, number = {1}, pages = {3}, pmid = {39367160}, issn = {1573-6792}, support = {HRA-POR-2013-246; MRCG-2018-02 and HRB ILP-POR-2022-046//Health Research Board of Ireland/ ; IceBucket Award; MRCG2018-02 to B.N., McManus/Apr22/888-791 to L.M. and McMackin/Oct20/972-799 to R.M//Irish/UK Motor Neurone Disease Research Foundation/ ; Project-ID 424778381-TRR 295//Deutsche Forschungsgemeinschaft/ ; Emerging Investigator Award HRB-EIA-2017-019//Health Research Board of Ireland/ ; GOIPD/2015/213 to B.N. and GOIPG/2017/1014 to R.M.//Irish Research Council/ ; /WT_/Wellcome Trust/United Kingdom ; 16/ ERCD/3854 and Royal Society/SFI URF\R1\221917 to L.M./SFI_/Science Foundation Ireland/Ireland ; multi-year grant 20-IIA-546//ALS Association/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology ; Male ; Female ; *Electroencephalography/methods ; Middle Aged ; Longitudinal Studies ; Aged ; Phenotype ; Brain/physiopathology ; Cognition/physiology ; Disease Progression ; Cognitive Dysfunction/physiopathology ; Adult ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is characterised primarily by motor system degeneration, with clinical evidence of cognitive and behavioural change in up to 50% of cases. We have shown previously that resting-state EEG captures dysfunction in motor and cognitive networks in ALS. However, the longitudinal development of these dysfunctional patterns, especially in networks linked with cognitive-behavioural functions, remains unclear. Longitudinal studies on non-motor changes in ALS are essential to further develop our understanding of disease progression, improve care and enhance the evaluation of new treatments. To address this gap, we examined 124 ALS individuals with 128-channel resting-state EEG recordings, categorised by cognitive impairment (ALSci, n = 25), behavioural impairment (ALSbi, n = 58), or non-impaired (ALSncbi, n = 53), with 12 participants meeting the criteria for both ALSci and ALSbi. Using linear mixed-effects models, we characterised the general and phenotype-specific longitudinal changes in brain network, and their association with cognitive performance, behaviour changes, fine motor symptoms, and survival. Our findings revealed a significant decline in [Formula: see text]-band spectral power over time in the temporal region along with increased [Formula: see text]-band power in the fronto-temporal region in the ALS group. ALSncbi participants showed widespread β-band synchrony decrease, while ALSci participants exhibited increased co-modulation correlated with verbal fluency decline. Longitudinal network-level changes were specific of ALS subgroups and correlated with motor, cognitive, and behavioural decline, as well as with survival. Spectral EEG measures can longitudinally track abnormal network patterns, serving as a candidate stratification tool for clinical trials and personalised treatments in ALS.}, } @article {pmid39366938, year = {2024}, author = {Hutchings, AJ and Hambrecht, B and Veh, A and Giridhar, NJ and Zare, A and Angerer, C and Ohnesorge, T and Schenke, M and Selvaraj, BT and Chandran, S and Sterneckert, J and Petri, S and Seeger, B and Briese, M and Stigloher, C and Bischler, T and Hermann, A and Damme, M and Sendtner, M and Lüningschrör, P}, title = {Plekhg5 controls the unconventional secretion of Sod1 by presynaptic secretory autophagy.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {8622}, pmid = {39366938}, issn = {2041-1723}, support = {LU 2347/3-1//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; VORAN-2 16LW066//Bundesministerium für Bildung und Forschung (Federal Ministry of Education and Research)/ ; }, mesh = {Animals ; Humans ; Male ; Mice ; *Amyotrophic Lateral Sclerosis/metabolism/genetics/pathology ; *Autophagy ; Disease Models, Animal ; Exocytosis ; *Guanine Nucleotide Exchange Factors/metabolism/genetics ; *Induced Pluripotent Stem Cells/metabolism ; Lysosomes/metabolism ; Mice, Inbred C57BL ; Mice, Knockout ; Mice, Transgenic ; *Motor Neurons/metabolism ; Presynaptic Terminals/metabolism ; rab GTP-Binding Proteins/metabolism/genetics ; *Superoxide Dismutase-1/metabolism/genetics ; }, abstract = {Increasing evidence suggests an essential function for autophagy in unconventional protein secretion (UPS). However, despite its relevance for the secretion of aggregate-prone proteins, the mechanisms of secretory autophagy in neurons have remained elusive. Here we show that the lower motoneuron disease-associated guanine exchange factor Plekhg5 drives the UPS of Sod1. Mechanistically, Sod1 is sequestered into autophagosomal carriers, which subsequently fuse with secretory lysosomal-related organelles (LROs). Exocytosis of LROs to release Sod1 into the extracellular milieu requires the activation of the small GTPase Rab26 by Plekhg5. Deletion of Plekhg5 in mice leads to the accumulation of Sod1 in LROs at swollen presynaptic sites. A reduced secretion of toxic ALS-linked SOD1[G93A] following deletion of Plekhg5 in SOD1[G93A] mice accelerated disease onset while prolonging survival due to an attenuated microglia activation. Using human iPSC-derived motoneurons we show that reduced levels of PLEKHG5 cause an impaired secretion of ALS-linked SOD1. Our findings highlight an unexpected pathophysiological mechanism that converges two motoneuron disease-associated proteins into a common pathway.}, } @article {pmid39365785, year = {2024}, author = {Putri, KD and Guntoro, D and Ardie, SW and Hariyadi, }, title = {A new amino acid substitution in the MvALS1 gene of metsulfuron-methyl resistant biotypes Monochoria vaginalis (Burm. f.) C. Presl from West Java, Indonesia.}, journal = {PloS one}, volume = {19}, number = {10}, pages = {e0308465}, pmid = {39365785}, issn = {1932-6203}, mesh = {Indonesia ; *Arylsulfonates/pharmacology ; *Amino Acid Substitution ; *Herbicide Resistance/genetics ; Herbicides/pharmacology ; Plant Proteins/genetics ; Mutation ; }, abstract = {The most bothersome weed in rice fields in the Indonesian province of West Java is Monochoria vaginalis (Burm. F.) C. Presl, an aquatic herbaceous plant. Metsulfuron-methyl has long been used in wetland rice in West Java with a high enough intensity. However, the case of Monochoria vaginalis resistance to metsulfuron-methyl herbicides in Indonesia has not been widely reported and investigated. The study aims to (1) classify the resistance level of M. vaginalis toward metsulfuron-methyl, (2) identify Target Site Resistance (TSR) mechanism mutations in the MvALS1 gene of the resistant biotype of M. vaginalis. The Whole Plant Pot Test method was utilized to assess the resistance level of Monochoria vaginalis. Following that, all samples were subjected to DNA sequencing using the PCR method to identify mutations in the MvALS1 gene from the resistant biotype. After then, this study used DUET, a server with an integrated computational methodology, to anticipate the effect of mutations on protein stability. The result showed that Monochoria vaginalis from Rawamerta, Karawang showed a moderate level of resistance to metsulfuron-methyl with a resistance ratio of 6.00, Patokbeusi, Subang showed a low level of resistance to metsulfuron-methyl with a resistance ratio of 3.89, compared to susceptible Monochoria vaginalis. Nucleotide base alignment in the MvALS1 gene revealed that base substitutions occurred in the Monochoria vaginalis biotype from Rawamerta and Patokbeusi, resulting in 5 amino acid substitutions: Ser-64-Ala, Asp-66-Glu, Asn-240-Asp, Glu-426-Asn, and Ser-469-Asn and Sukra: Ser-64-Ala, Asp-66-Glu, and Asn-240-Asp. The analysis showed that S64A, D66E, and N240D stabilize the protein, whereas E426N and S469N destabilize it. This study confirms for the first time that Ser-64-Ala, Asn-240-Asp, and Glu-426-Asn amino acid mutations were found in cases of M. vaginalis resistance to metsulfuron-methyl (ALS inhibitor).}, } @article {pmid39364420, year = {2024}, author = {Aiello, EN and Contarino, VE and Conte, G and Solca, F and Curti, B and Maranzano, A and Torre, S and Casale, S and Doretti, A and Colombo, E and Verde, F and Silani, V and Liu, C and Cinnante, C and Triulzi, FM and Morelli, C and Poletti, B and Ticozzi, N}, title = {QSM-detected iron accumulation in the cerebellar gray matter is selectively associated with executive dysfunction in non-demented ALS patients.}, journal = {Frontiers in neurology}, volume = {15}, number = {}, pages = {1426841}, pmid = {39364420}, issn = {1664-2295}, abstract = {BACKGROUND: This study aimed to assess whether quantitative susceptibility imaging (QSM)-based measures of iron accumulation in the cerebellum predict cognitive and behavioral features in non-demented amyotrophic lateral sclerosis (ALS) patients.

METHODS: A total of ALS patients underwent 3-T MRI and a clinical assessment using the ALS Functional Rating Scale-Revised (ALSFRS-R) and the Edinburgh Cognitive and Behavioural ALS Screen (ECAS). Regression models were applied to each subscale of the cognitive section of the ECAS and the ECAS-Carer Interview to examine the effect of QSM-based measures in white and gray matter (WM; GM) of the cerebellum, separately for right, left, and bilateral cerebellar regions of interest (ROIs). These effects were compared to those of cerebellar volumetrics in WM/GM, right and left hemispheres while controlling for demographics, disease status, and total intracranial volume.

RESULTS: Higher QSM measures of the cerebellar GM on the left, right, and bilateral sides significantly predicted (ps ≤ 0.003) a greater number of errors on the executive functioning (EF) subscale of the ECAS (ECAS-EF). Moreover, higher GM-related, QSM measures of the cerebellum were associated with an increased probability of a below-cut-off performance on the ECAS-EF (ps ≤ 0.024). No significant effects were observed for QSM measures of the cerebellar WM or for volumetric measures on the ECAS-EF. Other ECAS measures showed no significant effects. Bilateral QSM measures of the cerebellar GM also selectively predicted performance on backward digit span and social cognition tasks.

DISCUSSION: Iron accumulation within the cerebellar GM, particularly in the cerebellar cortices, may be associated with executive functioning deficits in non-demented ALS patients. Therefore, QSM-based measures could be useful for identifying the neural correlates of extra-motor cognitive deficits in ALS patients.}, } @article {pmid39364217, year = {2024}, author = {Samuel Olajide, T and Oyerinde, TO and Omotosho, OI and Okeowo, OM and Olajide, OJ and Ijomone, OM}, title = {Microglial senescence in neurodegeneration: Insights, implications, and therapeutic opportunities.}, journal = {Neuroprotection}, volume = {2}, number = {3}, pages = {182-195}, pmid = {39364217}, issn = {2770-730X}, support = {K43 TW011920/TW/FIC NIH HHS/United States ; }, abstract = {The existing literature on neurodegenerative diseases (NDDs) reveals a common pathological feature: the accumulation of misfolded proteins. However, the heterogeneity in disease onset mechanisms and the specific brain regions affected complicates the understanding of the diverse clinical manifestations of individual NDDs. Dementia, a hallmark symptom across various NDDs, serves as a multifaceted denominator, contributing to the clinical manifestations of these disorders. There is a compelling hypothesis that therapeutic strategies capable of mitigating misfolded protein accumulation and disrupting ongoing pathogenic processes may slow or even halt disease progression. Recent research has linked disease-associated microglia to their transition into a senescent state-characterized by irreversible cell cycle arrest-in aging populations and NDDs. Although senescent microglia are consistently observed in NDDs, few studies have utilized animal models to explore their role in disease pathology. Emerging evidence from experimental rat models suggests that disease-associated microglia exhibit characteristics of senescence, indicating that deeper exploration of microglial senescence could enhance our understanding of NDD pathogenesis and reveal novel therapeutic targets. This review underscores the importance of investigating microglial senescence and its potential contributions to the pathophysiology of NDDs, including Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. Additionally, it highlights the potential of targeting microglial senescence through iron chelation and senolytic therapies as innovative approaches for treating age-related NDDs.}, } @article {pmid39363643, year = {2025}, author = {Capelle, DP and Sabirin, W and Zulhairy-Liong, NA and Edgar, S and Goh, KJ and Ahmad-Annuar, A and Shahrizaila, N}, title = {Multistep modeling applied to a Malaysian ALS registry.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {26}, number = {1-2}, pages = {157-161}, doi = {10.1080/21678421.2024.2410280}, pmid = {39363643}, issn = {2167-9223}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/epidemiology/diagnosis ; *Registries ; Malaysia/epidemiology ; Male ; Female ; Middle Aged ; Aged ; Adult ; Disease Progression ; Incidence ; Age of Onset ; }, abstract = {OBJECTIVE: To apply the multistep model of pathogenesis in amyotrophic lateral sclerosis (ALS) to data from a multiethnic Malaysian registry.

METHODS: Clinical data, including age at symptom onset, was collected from 289 patients who presented to our multidisciplinary clinic from 2016 until 2024. A least squares linear regression model was constructed from the logarithm of approximated incidence and the logarithm of age. Population incidence was approximated by adjusting the absolute numbers of patients in 5 year groups by the size of the general population in the respective age group.

RESULTS: A linear relationship between log of incidence versus log of age was observed, with a slope of 4.57 (95% CI, 3.3-5.8) and an r[2] value of 0.93, suggesting a 6-step process.

CONCLUSION: Progression toward symptom onset in Malaysian ALS patients appears consistent with a multistep model of disease as observed in other cohorts.}, } @article {pmid39363348, year = {2024}, author = {Chevalier, E and Audrain, M and Ratnam, M and Ollier, R and Fuchs, A and Piorkowska, K and Pfeifer, A and Kosco-Vilbois, M and Seredenina, T and Afroz, T}, title = {Targeting the TDP-43 low complexity domain blocks spreading of pathology in a mouse model of ALS/FTD.}, journal = {Acta neuropathologica communications}, volume = {12}, number = {1}, pages = {156}, pmid = {39363348}, issn = {2051-5960}, support = {P01 AG019724/AG/NIA NIH HHS/United States ; P50 AG023501/AG/NIA NIH HHS/United States ; }, mesh = {Animals ; *Amyotrophic Lateral Sclerosis/pathology/metabolism ; *DNA-Binding Proteins/metabolism ; Mice ; *Disease Models, Animal ; *Frontotemporal Dementia/pathology/metabolism ; *Antibodies, Monoclonal/pharmacology ; Humans ; Mice, Transgenic ; }, abstract = {Abnormal cytoplasmic localization and accumulation of pathological transactive response DNA binding protein of 43 kDa (TDP-43) underlies several devastating diseases such as amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with TDP-43 pathology (FTLD-TDP). A key element is the correlation between disease progression and spatio-temporal propagation of TDP-43-mediated pathology in the central nervous system. Several lines of evidence support the concept of templated aggregation and cell to cell spreading of pathological TDP-43. To further investigate this mechanism in vivo, we explored the efficacy of capturing and masking the seeding-competent region of extracellular TDP-43 species. For this, we generated a novel monoclonal antibody (mAb), ACI-6677, that targets the pathogenic protease-resistant amyloid core of TDP-43. ACI-6677 has a picomolar binding affinity for TDP-43 and is capable of binding to all C-terminal TDP-43 fragments. In vitro, ACI-6677 inhibited TDP-43 aggregation and boosted removal of pathological TDP-43 aggregates by phagocytosis. When injecting FTLD-TDP brain extracts unilaterally in the CamKIIa-hTDP-43NLSm mouse model, ACI-6677 significantly limited the induction of phosphorylated TDP-43 (pTDP-43) inclusions. Strikingly, on the contralateral side, the mAb significantly prevented pTDP-43 inclusion appearance exemplifying blocking of the spreading process. Taken together, these data demonstrate for the first time that an immunotherapy targeting the protease-resistant amyloid core of TDP-43 has the potential to restrict spreading, substantially slowing or stopping progression of disease.}, } @article {pmid39362869, year = {2024}, author = {Ma, YY and Li, X and Yu, ZY and Luo, T and Tan, CR and Bai, YD and Xu, G and Sun, BD and Bu, XL and Liu, YH and Jin, WS and Gao, YQ and Zhou, XF and Liu, J and Wang, YJ}, title = {Oral antioxidant edaravone protects against cognitive deficits induced by chronic hypobaric hypoxia at high altitudes.}, journal = {Translational psychiatry}, volume = {14}, number = {1}, pages = {415}, pmid = {39362869}, issn = {2158-3188}, support = {92249305//National Natural Science Foundation of China (National Science Foundation of China)/ ; }, mesh = {Animals ; *Edaravone/pharmacology/administration & dosage ; *Cognitive Dysfunction/etiology/drug therapy/prevention & control ; Mice ; *Oxidative Stress/drug effects ; Male ; *Hypoxia/complications/drug therapy/metabolism ; *Altitude ; Antioxidants/pharmacology/administration & dosage ; Mice, Inbred C57BL ; Administration, Oral ; Hippocampus/drug effects/metabolism ; Disease Models, Animal ; Free Radical Scavengers/administration & dosage/pharmacology ; Brain/drug effects/metabolism ; }, abstract = {Chronic hypobaric hypoxia at high altitudes can impair cognitive functions, especially causing deficits in learning and memory, which require therapeutic intervention. Here, we showed that mice subjected to hypobaric hypoxia (simulating an altitude of 5000 m) for one month experienced significant cognitive impairment, accompanied by increased biomarker levels of oxidative stress in the brain and blood. Oral administration of a novel formulation of edaravone, a free radical scavenger approved for the treatment of ischaemic stroke and amyotrophic lateral sclerosis, significantly alleviated oxidative stress and cognitive impairments caused by chronic hypobaric hypoxia. Furthermore, oral edaravone treatment also mitigated neuroinflammation and restored hippocampal neural stem cell exhaustion. Additionally, periostin (Postn) is vital in the cognitive deficits caused by chronic hypobaric hypoxia and may be a molecular target of edaravone. In conclusion, our results suggest that oxidative stress plays a crucial role in the cognitive deficits caused by chronic hypobaric hypoxia and that oral edaravone is a potential medicine for protecting against cognitive deficits caused by chronic hypobaric hypoxia in high-altitude areas.}, } @article {pmid39362568, year = {2024}, author = {Velasquez, E and Savchenko, E and Marmolejo-Martínez-Artesero, S and Challuau, D and Aebi, A and Pomeshchik, Y and Lamas, NJ and Vihinen, M and Rezeli, M and Schneider, B and Raoul, C and Roybon, L}, title = {TNFα prevents FGF4-mediated rescue of astrocyte dysfunction and reactivity in human ALS models.}, journal = {Neurobiology of disease}, volume = {201}, number = {}, pages = {106687}, doi = {10.1016/j.nbd.2024.106687}, pmid = {39362568}, issn = {1095-953X}, mesh = {*Astrocytes/metabolism ; *Amyotrophic Lateral Sclerosis/metabolism/genetics/pathology ; Humans ; Animals ; Mice ; *Tumor Necrosis Factor-alpha/metabolism ; *Fibroblast Growth Factor 4/metabolism/genetics ; Induced Pluripotent Stem Cells/metabolism ; Superoxide Dismutase-1/genetics/metabolism ; Mice, Transgenic ; Disease Models, Animal ; Motor Neurons/metabolism/pathology ; Spinal Cord/metabolism/pathology ; }, abstract = {Astrocytes play a crucial role in the onset and progression of amyotrophic lateral sclerosis (ALS), a fatal disorder marked by the degeneration of motor neurons (MNs) in the central nervous system. Although astrocytes in ALS are known to be toxic to MNs, the pathological changes leading to their neurotoxic phenotype remain poorly understood. In this study, we generated human astrocytes from induced pluripotent stem cells (iPSCs) carrying the ALS-associated A4V mutation in superoxide dismutase 1 (SOD1) to examine early cellular pathways and network changes. Proteomic analysis revealed that ALS astrocytes are both dysfunctional and reactive compared to control astrocytes. We identified significant alterations in the levels of proteins linked to ALS pathology and the innate immune cGAS-STING pathway. Furthermore, we found that ALS astrocyte reactivity differs from that of control astrocytes treated with tumor necrosis factor alpha (TNFα), a key cytokine in inflammatory reactions. We then evaluated the potential of fibroblast growth factor (FGF) 2, 4, 16, and 18 to reverse ALS astrocyte phenotype. Among these, FGF4 successfully reversed ALS astrocyte dysfunction and reactivity in vitro. When delivered to the spinal cord of the SOD1[G93A] mouse model of ALS, FGF4 lowered astrocyte reactivity. However, this was not sufficient to protect MNs from cell death. Further analysis indicated that TNFα abrogated the reactivity reduction achieved by FGF4, suggesting that complete rescue of the ALS phenotype by FGF4 is hindered by ongoing complex neuroinflammatory processes in vivo. In summary, our data demonstrate that astrocytes generated from ALS iPSCs are inherently dysfunctional and exhibit an immune reactive phenotype. Effectively targeting astrocyte dysfunction and reactivity in vivo may help mitigate ALS and prevent MN death.}, } @article {pmid39361871, year = {2025}, author = {Fernandes, JPM and Garcia, LP and Gouhie, FA and Pereira, RC and Santos, DFD}, title = {Association between motor neuron disease and HIV infection: A systematic review of case reports.}, journal = {International journal of STD & AIDS}, volume = {36}, number = {1}, pages = {24-35}, doi = {10.1177/09564624241288283}, pmid = {39361871}, issn = {1758-1052}, mesh = {Humans ; *HIV Infections/drug therapy/complications ; *Motor Neuron Disease/complications ; Adult ; Male ; *Amyotrophic Lateral Sclerosis/drug therapy/complications ; Female ; Middle Aged ; Riluzole/therapeutic use ; }, abstract = {BACKGROUND: Motor neuron disease (MND) is a well-known group of neurodegenerative diseases, with amyotrophic lateral sclerosis (ALS) being the most common form. Since 1985, a possible association between MND/ALS and HIV infection has been described.

METHODS: We performed a systematic review of case reports and case series involving people living with HIV with MND/ALS through PubMed, Bireme, Embase, and Lilacs databases. The risk of bias was assessed using the Joanna Briggs Institute (JBI) Critical Appraisal Tool for Case Reports.

RESULTS: We analyzed 36 articles presenting 88 cases. The mean age was 41.6 years. Antiretroviral therapy (ART) was used by 89.8% and riluzole by 16.9%. First signs and symptoms were similarly present on cervical/upper (25%) and lumbosacral/lower limbs (23.9%), mostly with fasciculations (69.8%) and hyperreflexia (58.8%). MND had a progressive course in 32.9% patients and a clinical improve in 54.6% following ART. The mean survival of the 32 patients who died was 12.3 months and the mean survival of the living patients was 62 months. Respiratory failure was the main cause of death (35.7%).

CONCLUSIONS: MND/ALS may present differently in the people living with HIV as a rapidly progressive disease in younger people but with the potential to improve weakness and survival through antiretroviral therapy.}, } @article {pmid39361759, year = {2024}, author = {Wilkins, OG and Chien, MZYJ and Wlaschin, JJ and Barattucci, S and Harley, P and Mattedi, F and Mehta, PR and Pisliakova, M and Ryadnov, E and Keuss, MJ and Thompson, D and Digby, H and Knez, L and Simkin, RL and Diaz, JA and Zanovello, M and Brown, AL and Darbey, A and Karda, R and Fisher, EMC and Cunningham, TJ and Le Pichon, CE and Ule, J and Fratta, P}, title = {Creation of de novo cryptic splicing for ALS and FTD precision medicine.}, journal = {Science (New York, N.Y.)}, volume = {386}, number = {6717}, pages = {61-69}, pmid = {39361759}, issn = {1095-9203}, support = {ZIA HD008966/ImNIH/Intramural NIH HHS/United States ; MR/M008606/1/MRC_/Medical Research Council/United Kingdom ; 215593/WT_/Wellcome Trust/United Kingdom ; CC0102/WT_/Wellcome Trust/United Kingdom ; CC0102/MRC_/Medical Research Council/United Kingdom ; U54 NS123743/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Humans ; Mice ; *Amyotrophic Lateral Sclerosis/genetics/therapy ; Deep Learning ; *DNA-Binding Proteins/genetics/metabolism ; *Frontotemporal Dementia/genetics/therapy ; Gene Editing ; HEK293 Cells ; *Precision Medicine ; RNA Splice Sites ; *RNA Splicing ; RNA-Binding Proteins/metabolism/genetics ; }, abstract = {Loss of function of the RNA-binding protein TDP-43 (TDP-LOF) is a hallmark of amyotrophic lateral sclerosis (ALS) and other neurodegenerative disorders. Here we describe TDP-REG, which exploits the specificity of cryptic splicing induced by TDP-LOF to drive protein expression when and where the disease process occurs. The SpliceNouveau algorithm combines deep learning with rational design to generate customizable cryptic splicing events within protein-coding sequences. We demonstrate that expression of TDP-REG reporters is tightly coupled to TDP-LOF in vitro and in vivo. TDP-REG enables genomic prime editing to ablate the UNC13A cryptic donor splice site specifically upon TDP-LOF. Finally, we design TDP-REG vectors encoding a TDP-43/Raver1 fusion protein that rescues key pathological cryptic splicing events, paving the way for the development of precision therapies for TDP43-related disorders.}, } @article {pmid39360635, year = {2024}, author = {Abbassi, Y and Cappelli, S and Spagnolo, E and Gennari, A and Visani, G and Barattucci, S and Paron, F and Stuani, C and Droppelmann, CA and Strong, MJ and Buratti, E}, title = {Axon guidance genes are regulated by TDP-43 and RGNEF through long-intron removal.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {38}, number = {19}, pages = {e70081}, doi = {10.1096/fj.202400743RR}, pmid = {39360635}, issn = {1530-6860}, support = {//Fondazione Italiana di Ricerca per la Sclerosi Laterale Amiotrofica (AriSLA)/ ; //Temetry Family Foundation/ ; }, mesh = {*DNA-Binding Proteins/metabolism/genetics ; Humans ; Introns ; Guanine Nucleotide Exchange Factors/metabolism/genetics ; Animals ; Axon Guidance/genetics ; Motor Neurons/metabolism ; Amyotrophic Lateral Sclerosis/metabolism/genetics/pathology ; Gene Expression Regulation ; }, abstract = {Rho guanine nucleotide exchange factor (RGNEF) is a guanine nucleotide exchange factor (GEF) mainly involved in regulating the activity of Rho-family GTPases. It is a bi-functional protein, acting both as a guanine exchange factor and as an RNA-binding protein. RGNEF is known to act as a destabilizing factor of neurofilament light chain RNA (NEFL) and it could potentially contribute to their sequestration in nuclear cytoplasmic inclusions. Most importantly, RGNEF inclusions in the spinal motor neurons of ALS patients have been shown to co-localize with inclusions of TDP-43, the major well-known RNA-binding protein aggregating in the brain and spinal cord of human patients. Therefore, it can be hypothesized that loss-of-function of both proteins following aggregation may contribute to motor neuron death/survival in ALS patients. To further characterize their relationship, we have compared the transcriptomic profiles of neuronal cells depleted of TDP-43 and RGNEF and show that these two factors predominantly act in an antagonistic manner when regulating the expression of axon guidance genes. From a mechanistic point of view, our experiments show that the effect of these genes on the processivity of long introns can explain their mode of action. Taken together, our results show that loss-of-function of factors co-aggregating with TDP-43 can potentially affect the expression of commonly regulated neuronal genes in a very significant manner, potentially acting as disease modifiers. This finding further highlights that neurodegenerative processes at the RNA level are the result of combinatorial interactions between different RNA-binding factors that can be co-aggregated in neuronal cells. A deeper understanding of these complex scenarios may lead to a better understanding of pathogenic mechanisms occurring in patients, where more than one specific protein may be aggregating in their neurons.}, } @article {pmid39360554, year = {2025}, author = {Quigley, S and McNamara, B and Cronin, S}, title = {Alteration in ornithine metabolism due to mutation in ALDH18A1 masquerading as ALS in pregnancy.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {26}, number = {1-2}, pages = {172-174}, doi = {10.1080/21678421.2024.2410982}, pmid = {39360554}, issn = {2167-9223}, mesh = {Humans ; Female ; Pregnancy ; Adult ; *Mutation/genetics ; *Ornithine/metabolism ; *Amyotrophic Lateral Sclerosis/diagnosis/genetics ; *Aldehyde Dehydrogenase/genetics ; *Pregnancy Complications/genetics/diagnosis ; *Spastic Paraplegia, Hereditary/genetics/diagnosis ; Diagnosis, Differential ; }, abstract = {Clinical onset and exacerbation of autosomal dominant SPG9A hereditary spastic paraplegia, including reversible wasting, has been described during pregnancy. SPG9A is due to ALDH18A1 mutations resulting in proline and ornithine deficiency. We present the case of a 29 year old primagravida at 32 weeks who presented with six months of upper limb amyotrophic wasting on a background unrecognized progressive spasticity due to SPG9A. The wasting reversed significantly following delivery. Our report highlights the unusual clinical features including cataract and joint laxity which may suggest SPG9A, echoes the existing descriptions of pregnancy-related provocation of amyotrophy in this condition and documents the outcome of two subsequent pregnancies following dietary intervention.}, } @article {pmid39360074, year = {2024}, author = {Puri, SN and Raghuveer, R and Jachak, S and Tikhile, P}, title = {Exploring the Impact of Personalized Physical Therapy on a Patient With Motor Neuron Disorder: A Case Study.}, journal = {Cureus}, volume = {16}, number = {9}, pages = {e68373}, pmid = {39360074}, issn = {2168-8184}, abstract = {This case study examines the effect of a tailor-made physiotherapy regimen on an 85-year-old male patient who was suffering from bulbar motor neuron disease (MND) and had a history of stroke and COVID-19. The physiotherapy plan was designed to strategically address the patient's respiratory issues, generalized weakness affecting limb muscles, and speech and swallowing difficulties. Frequent evaluations made it possible to adjust the treatment plan, emphasizing a holistic strategy to improve the patient's overall quality of life. Improvements in scores on multiple functional scales and manual muscle testing were shown by outcome measures and follow-up evaluations. This case emphasizes how important customized physiotherapy is for maximizing functional outcomes and enhancing the quality of life for patients dealing with the complicated conditions of bulbar MND.}, } @article {pmid39359088, year = {2025}, author = {Kim, K}, title = {Carboplatin restores neuronal toxicity in FUS-linked amyotrophic lateral sclerosis.}, journal = {Neural regeneration research}, volume = {20}, number = {8}, pages = {2319-2320}, pmid = {39359088}, issn = {1673-5374}, } @article {pmid39353548, year = {2025}, author = {Bosco, DB and Kremen, V and Haruwaka, K and Zhao, S and Wang, L and Ebner, BA and Zheng, J and Xie, M and Dheer, A and Perry, JF and Barath, A and Nguyen, AT and Worrell, GA and Wu, LJ}, title = {Microglial TREM2 promotes phagocytic clearance of damaged neurons after status epilepticus.}, journal = {Brain, behavior, and immunity}, volume = {123}, number = {}, pages = {540-555}, pmid = {39353548}, issn = {1090-2139}, support = {R01 NS088627/NS/NINDS NIH HHS/United States ; R01 NS112144/NS/NINDS NIH HHS/United States ; R35 NS132326/NS/NINDS NIH HHS/United States ; RF1 AG082314/AG/NIA NIH HHS/United States ; }, mesh = {*Receptors, Immunologic/metabolism/genetics ; Animals ; *Status Epilepticus/metabolism/genetics ; *Microglia/metabolism ; *Membrane Glycoproteins/metabolism/genetics ; *Mice, Knockout ; Male ; *Phagocytosis/physiology/genetics ; Mice ; *Neurons/metabolism ; Humans ; Disease Models, Animal ; Kainic Acid ; Mice, Inbred C57BL ; Epilepsy, Temporal Lobe/metabolism/genetics ; Seizures/metabolism/genetics ; Antigens, CD/metabolism ; Antigens, Differentiation, Myelomonocytic/metabolism ; }, abstract = {In the central nervous system, triggering receptor expressed on myeloid cells 2 (TREM2) is exclusively expressed by microglia and is critical for microglial proliferation, migration, and phagocytosis. Microglial TREM2 plays an important role in neurodegenerative diseases, such as Alzheimer's disease and amyotrophic lateral sclerosis. However, little is known about how TREM2 affects microglial function within epileptogenesis. To investigate this, we utilized male TREM2 knockout (KO) mice within the intra-amygdala kainic acid seizure model. Electroencephalographic analysis, immunocytochemistry, and RNA sequencing revealed that TREM2 deficiency significantly promoted seizure-induced pathology. We found that TREM2 KO increased both the severity of acute status epilepticus and the number of spontaneous recurrent seizures characteristic of chronic focal epilepsy. Phagocytic clearance of damaged neurons by microglia was also impaired by TREM2 KO and reduced phagocytic activity correlated with increased spontaneous seizures. Analysis of human tissue from patients who underwent surgical resection for drug resistant temporal lobe epilepsy also showed a negative correlation between expression of the microglial phagocytic marker CD68 and focal to bilateral tonic-clonic generalized seizure history. These results indicate that microglial TREM2 and phagocytic activity are important to epileptogenic pathology.}, } @article {pmid39355693, year = {2024}, author = {Leger, D and Bater, S and Paulin, MV and Linn, K and Taylor, S and Shelton, GD}, title = {Presumptive motor neuron degeneration in an adult cat.}, journal = {The Canadian veterinary journal = La revue veterinaire canadienne}, volume = {65}, number = {10}, pages = {1034-1040}, pmid = {39355693}, issn = {0008-5286}, mesh = {Cats ; Male ; Animals ; *Cat Diseases/pathology/diagnosis/drug therapy ; *Motor Neuron Disease/veterinary/pathology/diagnosis ; Prednisolone/therapeutic use ; Immunosuppressive Agents/therapeutic use ; Motor Neurons/pathology ; Muscular Atrophy/veterinary/pathology ; Muscle, Skeletal/pathology ; }, abstract = {An 8-year-old neutered male Bengal cat was referred because of a 1-year history of progressive and relapsing generalized muscle weakness and muscle atrophy. Before referral, the cat was treated with immunosuppressive doses of oral prednisolone, intermittently for 6 mo, and had responded well when the immunosuppressive dose was maintained. Generalized paresis, diffuse muscle atrophy, and diminished spinal reflexes were present in all limbs, consistent with a generalized lower motor neuron disease. Histopathologic evaluation of muscle biopsies confirmed a pattern of muscle fiber atrophy consistent with chronic and severe denervation. No specific abnormalities were identified in the nerve biopsy or within intramuscular nerve branches. A presumptive antemortem diagnosis of an adult-onset motor neuron degeneration resembling amyotrophic lateral sclerosis (ALS) or spinal muscle atrophy was suspected. However, given the response to immunosuppressive doses of corticosteroids, an autoimmune process or other degenerative process could not be definitively excluded. Key clinical message: In this case, an adult cat had a chronic, progressive history of lower motor neuron weakness and absent spinal reflexes; biopsies revealed a neurogenic pattern of muscle fiber atrophy and histologically normal peripheral nerve and intramuscular nerve branches. Although reports of motor neuron disease are rare in the veterinary literature, this case report highlights the importance of muscle and nerve biopsies that lead to a presumptive diagnosis of motor neuron degeneration.}, } @article {pmid39355247, year = {2024}, author = {Yang, JL and Wu, JY and Liu, JJ and Zheng, GQ}, title = {Herbal medicines for SOD1[G93A] mice of amyotrophic lateral sclerosis: preclinical evidence and possible immunologic mechanism.}, journal = {Frontiers in immunology}, volume = {15}, number = {}, pages = {1433929}, pmid = {39355247}, issn = {1664-3224}, mesh = {*Amyotrophic Lateral Sclerosis/drug therapy/immunology/genetics ; Animals ; Mice ; *Disease Models, Animal ; Mice, Transgenic ; Humans ; Superoxide Dismutase-1/genetics ; Herbal Medicine ; }, abstract = {Currently, there is no cure or effective treatment for Amyotrophic Lateral Sclerosis (ALS). The mechanisms underlying ALS remain unclear, with immunological factors potentially playing a significant role. Adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA), a systematic review of preclinical studies was conducted, searching seven databases including PubMed, covering literature from the inception of the databases to April 10, 2024. Methodological quality of the included literature was assessed using CAMARADES, while the risk of bias in the included studies was evaluated using SYRCLE's ROB tool. Review Manager 5.4.1 statistical software was used for meta-analysis of the outcomes. The scoping review followed the Joanna Briggs Institute Methodological Guidelines and reporting of this review followed the PRISMA-extension for Scoping Reviews (PRISMA -ScR) checklist to explore the immunological mechanisms of Herbal Medicine (HM) in treating ALS. This systematic review and meta-analysis involved 18 studies with a total of 443 animals. The studies scored between 4 to 8 for methodological quality and 3 to 7 for risk of bias, both summing up to 10.A remarkable effects of HM in ALS mice, including onset time(Standardized Mean Difference(SMD): 1.75, 95% Confidence Interval(CI) (1.14 ~ 2.36), Z = 5.60, P < 0.01), survival time(SMD = 1.42, 95% CI (0.79 ~ 2.04), Z = 4.44, P < 0.01), stride length(SMD=1.90, 95% CI (1.21 to 2.59), Z = 5.39, P < 0.01) and duration time (Mean Difference(MD)=6.79, 95% CI [-0.28, 13.87], Z=1.88, P =0.06), showing HM's certain efficiency in treating ALS mice. The scoping review ultimately included 35 articles for review. HMs may treat ALS through mechanisms such as combating oxidative stress, excitatory amino acid toxicity, and calcium cytotoxicity, understanding and exploring the mechanisms will bring hope to patients. Individual herbs and their formulations within HM address ALS through a variety of immune pathways, including safeguarding the blood-brain barrier, countering neuroinflammation, impeding complement system activation, mitigating natural killer cell toxicity, and regulating T cell-mediated immune pathways. The preclinical evidence supports the utilization of HM as a conventional treatment for ALS mice. Growing evidence indicates that HM may potentially delay neurological degeneration in ALS by activating diverse signaling pathways, especially immune pathways.}, } @article {pmid39352715, year = {2024}, author = {Sung, SF and Hu, YH and Chen, CY}, title = {Disambiguating Clinical Abbreviations by One-to-All Classification: Algorithm Development and Validation Study.}, journal = {JMIR medical informatics}, volume = {12}, number = {}, pages = {e56955}, pmid = {39352715}, issn = {2291-9694}, mesh = {*Natural Language Processing ; *Electronic Health Records ; Humans ; *Algorithms ; *Abbreviations as Topic ; }, abstract = {BACKGROUND: Electronic medical records store extensive patient data and serve as a comprehensive repository, including textual medical records like surgical and imaging reports. Their utility in clinical decision support systems is substantial, but the widespread use of ambiguous and unstandardized abbreviations in clinical documents poses challenges for natural language processing in clinical decision support systems. Efficient abbreviation disambiguation methods are needed for effective information extraction.

OBJECTIVE: This study aims to enhance the one-to-all (OTA) framework for clinical abbreviation expansion, which uses a single model to predict multiple abbreviation meanings. The objective is to improve OTA by developing context-candidate pairs and optimizing word embeddings in Bidirectional Encoder Representations From Transformers (BERT), evaluating the model's efficacy in expanding clinical abbreviations using real data.

METHODS: Three datasets were used: Medical Subject Headings Word Sense Disambiguation, University of Minnesota, and Chia-Yi Christian Hospital from Ditmanson Medical Foundation Chia-Yi Christian Hospital. Texts containing polysemous abbreviations were preprocessed and formatted for BERT. The study involved fine-tuning pretrained models, ClinicalBERT and BlueBERT, generating dataset pairs for training and testing based on Huang et al's method.

RESULTS: BlueBERT achieved macro- and microaccuracies of 95.41% and 95.16%, respectively, on the Medical Subject Headings Word Sense Disambiguation dataset. It improved macroaccuracy by 0.54%-1.53% compared to two baselines, long short-term memory and deepBioWSD with random embedding. On the University of Minnesota dataset, BlueBERT recorded macro- and microaccuracies of 98.40% and 98.22%, respectively. Against the baselines of Word2Vec + support vector machine and BioWordVec + support vector machine, BlueBERT demonstrated a macroaccuracy improvement of 2.61%-4.13%.

CONCLUSIONS: This research preliminarily validated the effectiveness of the OTA method for abbreviation disambiguation in medical texts, demonstrating the potential to enhance both clinical staff efficiency and research effectiveness.}, } @article {pmid39352708, year = {2024}, author = {Crose, JJ and Crose, A and Ransom, JT and Lightner, AL}, title = {Bone marrow mesenchymal stem cell-derived extracellular vesicle infusion for amyotrophic lateral sclerosis.}, journal = {Neurodegenerative disease management}, volume = {14}, number = {3-4}, pages = {111-117}, pmid = {39352708}, issn = {1758-2032}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy ; *Extracellular Vesicles ; Male ; Middle Aged ; Female ; Pilot Projects ; Aged ; Mesenchymal Stem Cells ; Mesenchymal Stem Cell Transplantation/methods ; Infusions, Intravenous ; Adult ; Treatment Outcome ; }, abstract = {Background: In this pilot safety study, we hypothesized that a human bone marrow stem cell-derived extracellular vesicle (hBM-MSC EV) investigational product (IP) would be safe and exhibit potential efficacy in amyotrophic lateral sclerosis (ALS) patients.Methods: Ten ALS patients received two 10-ml intravenous infusions of the IP given 1 month apart and evaluated over 3 months.Results: There were no serious adverse events or adverse events related to the IP and 30% of subjects' ALS functional rating scale-revised (ALSFRS-R) scores did not decline.Conclusion: HBM-MSC EVs appear safe in ALS patients. This early investigation suggests a controlled study of EVs for the treatment of ALS is warranted.}, } @article {pmid39351695, year = {2024}, author = {Wang, PS and Yang, XX and Wei, Q and Lv, YT and Wu, ZY and Li, HF}, title = {Clinical characterization and founder effect analysis in Chinese amyotrophic lateral sclerosis patients with SOD1 common variants.}, journal = {Annals of medicine}, volume = {56}, number = {1}, pages = {2407522}, pmid = {39351695}, issn = {1365-2060}, mesh = {Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Age of Onset ; *Amyotrophic Lateral Sclerosis/genetics ; China/epidemiology ; East Asian People ; Exome Sequencing ; *Founder Effect ; Genetic Association Studies ; Haplotypes ; Mutation ; Phenotype ; *Superoxide Dismutase-1/genetics ; }, abstract = {OBJECTIVE: In the Asian population, SOD1 variants are the most common cause of amyotrophic lateral sclerosis (ALS). To date, more than 200 variants have been reported in SOD1. This study aimed to summarize the genotype-phenotype correlation and determine whether the patients carrying common variants derive from a common ancestor.

METHODS: A total of 103 sporadic ALS (SALS) and 11 familial ALS (FALS) probands were included and variants were screened by whole exome sequencing. Functional analyses were performed on fibroblasts derived from patients with SOD1 p.V48A and control. Haplotype analysis was performed in the probands with p.H47R or p.V48A and their familial members.

RESULTS: A total of 25 SOD1 variants were identified in 44 probands, in which p.H47R, p.V48A and p.C112Y variants were the most common variants. 94.3% and 60% of patients with p.H47R or p.V48A had lower limb onset with predominant lower motor neurons (LMNs) involvement. Patients with p.H47R had a slow progression and prolonged survival time, while patients with p.V48A exhibited a duration of 2-5 years. Patients with p.C112Y variant showed remarkable phenotypic variation in age at onset and disease course. SOD1[V48A] fibroblasts showed mutant SOD1 aggregate formation, enhanced intracellular reactive oxygen species level, and decreased mitochondrial membrane potential compared to the control fibroblast. Haplotype analysis showed that seven families had two different haplotypes. p.H47R and p.V48A variants did not originate from a common founder.

CONCLUSIONS: Our study expanded the understanding of the genotype-phenotype correlation of ALS with SOD1 variants and revealed that the common p.H47R or p.V48A variant did not have a founder effect.}, } @article {pmid39351260, year = {2024}, author = {Gao, FQ and Zhu, JQ and Feng, XD}, title = {Innovative mesenchymal stem cell treatments for fatty liver disease.}, journal = {World journal of stem cells}, volume = {16}, number = {9}, pages = {846-853}, pmid = {39351260}, issn = {1948-0210}, abstract = {The incidence of non-alcoholic fatty liver disease (NAFLD) and alcohol-associated liver disease (ALD) is increasing year by year due to changes in the contemporary environment and dietary structure, and is an important public health problem worldwide. There is an urgent need to continuously improve the understanding of their disease mechanisms and develop novel therapeutic strategies. Mesenchymal stem cells (MSCs) have shown promise as a potential therapeutic strategy in therapeutic studies of NAFLD and ALD. NAFLD and ALD have different triggers and their specific mechanisms of disease progression are different, but both involve disease processes such as hepatocellular steatosis and potential fibrosis, cirrhosis, and even hepatocellular carcinoma. MSCs have metabolic regulatory, anti-apoptotic, antioxidant, and immunomodulatory effects that together promote liver injury repair and functional recovery, and have demonstrated positive results in preclinical studies. This editorial is a continuum of Jiang et al's review focusing on the advantages and limitations of MSCs and their derivatives as therapeutics for NAFLD and ALD. They detail how MSCs attenuate the progression of NAFLD by modulating molecular pathways involved in glucolipid metabolism, inflammation, oxidative stress, endoplasmic reticulum stress, and fibrosis. Based on recent advances, we discuss MSCs and their derivatives as therapeutic strategies for NAFLD and ALD, providing useful information for their clinical application.}, } @article {pmid39350404, year = {2025}, author = {Mohan, M and Mannan, A and Kakkar, C and Singh, TG}, title = {Nrf2 and Ferroptosis: Exploring Translational Avenues for Therapeutic Approaches to Neurological Diseases.}, journal = {Current drug targets}, volume = {26}, number = {1}, pages = {33-58}, pmid = {39350404}, issn = {1873-5592}, mesh = {*Ferroptosis/physiology/drug effects ; Humans ; *NF-E2-Related Factor 2/metabolism/genetics ; Animals ; *Nervous System Diseases/metabolism/drug therapy ; Reactive Oxygen Species/metabolism ; Oxidative Stress ; Iron/metabolism ; }, abstract = {Nrf2, a crucial protein involved in defense mechanisms, particularly oxidative stress, plays a significant role in neurological diseases (NDs) by reducing oxidative stress and inflammation. NDs, including Alzheimer's, Parkinson's, Huntington's, amyotrophic lateral sclerosis, stroke, epilepsy, schizophrenia, depression, and autism, exhibit ferroptosis, iron-dependent regulated cell death resulting from lipid and iron-dependent reactive oxygen species (ROS) accumulation. Nrf2 has been shown to play a critical role in regulating ferroptosis in NDs. Age-related decline in Nrf2 expression and its target genes (HO-1, Nqo-1, and Trx) coincides with increased iron-mediated cell death, leading to ND onset. The modulation of iron-dependent cell death and ferroptosis by Nrf2 through various cellular and molecular mechanisms offers a potential therapeutic pathway for understanding the pathological processes underlying these NDs. This review emphasizes the mechanistic role of Nrf2 and ferroptosis in multiple NDs, providing valuable insights for future research and therapeutic approaches.}, } @article {pmid39349916, year = {2025}, author = {Soliman, R and Onbool, E and Omran, K and Fahmy, N}, title = {Clinical and epidemiological characteristics of amyotrophic lateral sclerosis in an Egyptian cohort.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {46}, number = {3}, pages = {1225-1236}, pmid = {39349916}, issn = {1590-3478}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/epidemiology/diagnosis/physiopathology ; Egypt/epidemiology ; Male ; Female ; Middle Aged ; Adult ; Age of Onset ; Disease Progression ; Prospective Studies ; Aged ; Cohort Studies ; Young Adult ; }, abstract = {OBJECTIVE: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder associated with progressive loss of motor neurons. It is a growing and underestimated disease, prompting this epidemiological study to describe the characteristics of ALS in Egyptian patients.

METHODS: This is a prospective hospital based study. ALS patients were recruited consecutively from Neuromuscular Unit in Ain Shams university Hospital from December 2018 to June 2023. Demographic data and disease related parameters were recorded.

RESULTS: 203 ALS patients had a mean age of onset equal 39 years and an inter quartile range IQR of (28.00-51.00). 76% of the cases were spinal onset ALS. Median disease duration was 2 years with IQR of (1-4 years); male to female ratio was 2.5:1; 18% of patients were familial ALS (FALS), while 19% were Juvenile ALS (JALS). Median diagnostic delay was 12 ± (6-36) months. Median Amyotrophic Lateral Sclerosis Functional Rating Scale Revised scores (ALSFRS-R) at presentation was 34.5 IQR of (26.00-40.00). Also, the mean rate of disease progression ALSFRS-R decline [points/month] was 0.76 ± 0.51.

CONCLUSION: Our cohort was characterized by a younger age of onset, male predominance, more familial cases, within average Initial ALSFRS-R scores as well as diagnostic delay. Juvenile ALS patients were much more common in our population. These findings suggest an influential presence of genetic and epigenetic factors affecting the clinical phenotype of Egyptian ALS patients.}, } @article {pmid39349171, year = {2024}, author = {Khanna, RK and Catanese, S and Mortemousque, G and Dupuy, C and Lefevre, A and Emond, P and Beltran, S and Gissot, V and Pisella, PJ and Blasco, H and Corcia, P}, title = {Metabolomics of basal tears in amyotrophic lateral sclerosis: A cross-sectional study.}, journal = {The ocular surface}, volume = {34}, number = {}, pages = {363-369}, doi = {10.1016/j.jtos.2024.09.005}, pmid = {39349171}, issn = {1937-5913}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism/diagnosis ; Male ; Female ; Prospective Studies ; Middle Aged ; *Metabolomics/methods ; Cross-Sectional Studies ; Aged ; *Tears/metabolism ; Case-Control Studies ; Biomarkers/metabolism ; Chromatography, High Pressure Liquid ; Adult ; }, abstract = {PURPOSE: Amyotrophic lateral sclerosis (ALS) clinical variability, along with the lack of conclusive diagnostic instruments, result in average diagnosis delays of 9 months. This study aimed to assess whether metabolomic profiling of basal tears in ALS patients could act as a biological marker for diagnosing ALS, predicting prognosis, and discriminating between endophenotypes.

METHODS: A single-center prospective case-control study was conducted in France from September 2021 to March 2023 including patients with ALS according to the revised EI Escorial criteria. Two microliters of basal tears were collected using microcapillary glass tubes and analyzed with ultra-high performance liquid chromatography coupled with mass spectrometry. Both univariate and multivariate analyses were performed.

RESULTS: Twenty-five patients with ALS and 30 controls were included. No significant differences in metabolite levels were found between ALS and control groups (p > 0.05). The basal tear metabolome significantly discriminated bulbar and spinal forms of ALS based on 6 metabolites, among which 5 were decreased (aniline, trigonelline, caffeine, theophylline and methyl beta-D-galactoside) in the bulbar form and 1 was decreased in the spinal form (dodecanedioic acid).

CONCLUSION: This study represents the first prospective analysis of basal tear metabolomics in individuals with ALS. Despite the inability to distinguish between ALS patients and controls based on metabolic signatures, these findings could contribute to understanding the phenotypic diversity of ALS. Notably, distinct metabolic profiles were identified that differentiate between the bulbar and spinal forms of the disease.}, } @article {pmid39349054, year = {2025}, author = {Simpson, JT and Nordham, KD and Tatum, D and Haut, ER and Ali, A and Maher, Z and Goldberg, AJ and Tatebe, LC and Chang, G and Taghavi, S and Raza, S and Toraih, E and Mendiola Plá, M and Ninokawa, S and Anderson, C and Maluso, P and Keating, J and Burruss, S and Reeves, M and Craugh, LE and Shatz, DV and Bhupathi, A and Spalding, MC and LaRiccia, A and Bird, E and Noorbakhsh, MR and Babowice, J and Nelson, MC and Jacobson, LE and Williams, J and Vella, M and Dellonte, K and Hayward, TZ and Holler, E and Lieser, MJ and Berne, JD and Mederos, DR and Askari, R and Okafor, B and Etchill, E and Fang, R and Roche, SL and Whittenburg, L and Bernard, AC and Haan, JM and Lightwine, KL and Norwood, SH and Murry, J and Gamber, MA and Carrick, MM and Bugaev, N and Tatar, A}, title = {Stop the Bleed-Wait for the Ambulance or Get in the Car and Drive? A Post Hoc Analysis of an EAST Multicenter Trial.}, journal = {The American surgeon}, volume = {91}, number = {2}, pages = {233-241}, doi = {10.1177/00031348241265135}, pmid = {39349054}, issn = {1555-9823}, mesh = {Humans ; Male ; Female ; Adult ; Middle Aged ; *Ambulances ; *Hemorrhage/prevention & control/etiology/mortality/therapy ; *Wounds, Penetrating/therapy/mortality/complications ; *Transportation of Patients/methods ; Trauma Centers ; *Emergency Medical Services/methods ; Propensity Score ; }, abstract = {Background: The Stop the Bleed campaign gives bystanders an active role in prehospital hemorrhage control. Whether extending bystanders' role to private vehicle transport (PVT) for urban penetrating trauma improves survival is unknown, but past research has found benefit to police and PVT. We hypothesized that for penetrating trauma in an urban environment, where prehospital procedures have been proven harmful, PVT improves outcomes compared to any EMS or advanced life support (ALS) transport.Methods: Post-hoc analysis of an EAST multicenter trial was performed on adult patients with penetrating torso/proximal extremity trauma at 25 urban trauma centers from 5/2019-5/2020. Patients were allocated to PVT and any EMS or ALS transport using nearest neighbor propensity score matching. Univariate analyses included Wilcoxon signed rank or McNemar's Test and logistic regression.Results: Of 1999 penetrating trauma patients in urban settings, 397 (19.9%) had PVT, 1433 (71.7%) ALS transport, and 169 (8.5%) basic life support (BLS) transport. Propensity matching yielded 778 patients, distributed equally into balanced groups. PVT patients were primarily male (90.5%), Black (71.2%), and sustained gunshot wounds (68.9%). ALS transport had significantly higher ED mortality (3.9% vs 1.9%, P = 0.03). There was no difference in in-hospital mortality rate, hospital LOS, or complications for all EMS or ALS only transport patients.Conclusion: Compared to PVT, ALS, which provides more prehospital procedures than BLS, provided no survival benefit for penetrating trauma patients in urban settings. Bystander education incorporating PVT for early arrival of penetrating trauma patients in urban settings to definitive care merits further investigation.}, } @article {pmid39347895, year = {2025}, author = {Yin, KF and Chen, T and Gu, XJ and Jiang, Z and Su, WM and Duan, QQ and Wen, XJ and Cao, B and Li, JR and Chi, LY and Chen, YP}, title = {Identification of Potential Causal Genes for Neurodegenerative Diseases by Mitochondria-Related Genome-Wide Mendelian Randomization.}, journal = {Molecular neurobiology}, volume = {62}, number = {3}, pages = {3892-3902}, pmid = {39347895}, issn = {1559-1182}, support = {2022NSFSC0749//National Natural Science Fund of Sichuan/ ; 2023HXFH032//1·3·5 project for disciplines of excellence-Clinical Research Fund, West China Hospital, Sichuan University/ ; 2022YFC2703101//National Key Research and Development Program of China/ ; 2023YFS0269//Science and Technology Bureau Fund of Sichuan Province/ ; 81971188//National Natural Science Fund of China/ ; C2023124417//National Innovation and Entrepreneurship Training Program for College Students/ ; }, mesh = {Humans ; *Mendelian Randomization Analysis/methods ; *Neurodegenerative Diseases/genetics ; *Genome-Wide Association Study/methods ; *Mitochondria/genetics ; *Genetic Predisposition to Disease ; DNA, Mitochondrial/genetics ; Quantitative Trait Loci/genetics ; Bayes Theorem ; }, abstract = {Current research lacks comprehensive investigations into the potential causal link between mitochondrial-related genes and the risk of neurodegenerative diseases (NDDs). We aimed to identify potential causative genes for five NDDs through an examination of mitochondrial-related gene expression levels. Through the integration of summary statistics from expression quantitative trait loci (eQTL) datasets (human blood and brain tissue), mitochondrial DNA copy number (mtDNA-CN), and genome-wide association studies (GWAS) datasets of five NDDs from European ancestry, we conducted a Mendelian randomization (MR) analysis to explore the potential causal relationship between mitochondrial-related genes and Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and Lewy body dementia (LBD). Sensitivity analysis and Bayesian colocalization were employed to validate this causal relationship. Through MR analysis, we have identified potential causal relationships between 12 mitochondria-related genes and AD, PD, ALS, and FTD overlapping with motor neuron disease (FTD_MND) in human blood or brain tissue. Bayesian colocalization analysis further confirms 9 causal genes, including NDUFS2, EARS2, and MRPL41 for AD; NDUFAF2, MALSU1, and METTL8 for PD; MYO19 and MRM1 for ALS; and FASTKD1 for FTD_MND. Importantly, in both human blood and brain tissue, NDUFS2 exhibits a significant pathogenic effect on AD, while NDUFAF2 demonstrates a robust protective effect on PD. Additionally, the mtDNA-CN plays a protected role in LBD (OR = 0.62, p = 0.031). This study presents evidence establishing a causal relationship between mitochondrial dysfunction and NDDs. Furthermore, the identified candidate genes may serve as potential targets for drug development aimed at preventing NDDs.}, } @article {pmid39347334, year = {2024}, author = {Aljehani, NS and Al-Gunaid, ST and Hobani, AH and Alhinti, MF and Khubrani, YA and Abu-Hamoud, LM and Alrayes, AA and Alharbi, LB and Sultan, AA and Turkistani, DA and Naiser, SS and Albraik, L and Alakel, AM and Alotaibi, M and Asiri, AY}, title = {Ultrasound Blood-Brain Barrier Opening and Aducanumab in Alzheimer's Disease: A Systematic Review and Meta-Analysis.}, journal = {Cureus}, volume = {16}, number = {8}, pages = {e68008}, pmid = {39347334}, issn = {2168-8184}, abstract = {The blood-brain barrier (BBB) presents a significant challenge in treating Alzheimer's disease, as it restricts the delivery of therapeutic medications to brain tissue. Reversible breaking of the BBB using low-intensity focused ultrasound guided by magnetic resonance imaging (MRI) may benefit patients with Alzheimer's disease and other neurological illnesses, such as brain tumors, amyotrophic lateral sclerosis, and Parkinson's disease. This systematic study and meta-analysis aimed to assess aducanumab and the ultrasonography of BBB opening in Alzheimer's patients. According to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), the study was conducted by searching six digital repositories for relevant scholarly literature, focusing on English papers published between 2015 and 2024; the data was extracted using an Excel sheet, and data was analyzed using Revman 5.4.1 software. The study's findings indicate that the groups receiving ultrasound and aducanumab treatment benefited from it; however, overall, the effect was not statistically significant (P=0.29) at 95% CI 0.86 (0.75, 1.00). With regard to side effects, the results indicate that the treatment had fewer side effects compared to the control group; however, the difference was not statistically significant (p=0.94) at 95% CI 0.93 (0.70, 1.22). The study found a positive effect of ultrasound and aducanumab on the treatment groups, but it was not statistically significant. The control group had less side effects than the treatment group. Therefore, future studies should focus on the quantity or combination of the drug that yields more effective results.}, } @article {pmid39346793, year = {2024}, author = {Ghaderi, S and Mohammadi, S and Fatehi, F}, title = {Calcium accumulation or iron deposition: Delving into the temporal sequence of amyotrophic lateral sclerosis pathophysiology in the primary motor cortex.}, journal = {Ibrain}, volume = {10}, number = {3}, pages = {375-377}, pmid = {39346793}, issn = {2769-2795}, abstract = {Amyotrophic lateral sclerosis (ALS) causes progressive motor neuron degeneration, but an in vivo understanding of its early pathology remains limited. A recent study used topographic layer imaging to investigate iron and calcium accumulation in the primary motor cortex (M1) of patients with ALS compared with controls. Despite the preserved cortical thickness, ALS patients showed increased iron in layer 6 and calcium accumulation in layer 5a and the superficial layer. Calcium accumulation was particularly prominent in the low-myelin borders, potentially preceding the demyelination. This study reveals a novel in vivo pathology in ALS, suggesting that calcium dysregulation may precede iron accumulation and contribute to early M1 cell degeneration. Further investigation using quantitative susceptibility mapping and complementary techniques, such as diffusion kurtosis imaging, along with ultrahigh-field magnetic resonance imaging, into the role of calcium and early intervention strategies is warranted.}, } @article {pmid39346681, year = {2024}, author = {Fisher, RMA and Torrente, MP}, title = {Histone post-translational modification and heterochromatin alterations in neurodegeneration: revealing novel disease pathways and potential therapeutics.}, journal = {Frontiers in molecular neuroscience}, volume = {17}, number = {}, pages = {1456052}, pmid = {39346681}, issn = {1662-5099}, support = {R15 NS125394/NS/NINDS NIH HHS/United States ; }, abstract = {Alzheimer's disease (AD), Parkinson's disease (PD), Frontotemporal Dementia (FTD), and Amyotrophic lateral sclerosis (ALS) are complex and fatal neurodegenerative diseases. While current treatments for these diseases do alleviate some symptoms, there is an imperative need for novel treatments able to stop their progression. For all of these ailments, most cases occur sporadically and have no known genetic cause. Only a small percentage of patients bear known mutations which occur in a multitude of genes. Hence, it is clear that genetic factors alone do not explain disease occurrence. Chromatin, a DNA-histone complex whose basic unit is the nucleosome, is divided into euchromatin, an open form accessible to the transcriptional machinery, and heterochromatin, which is closed and transcriptionally inactive. Protruding out of the nucleosome, histone tails undergo post-translational modifications (PTMs) including methylation, acetylation, and phosphorylation which occur at specific residues and are connected to different chromatin structural states and regulate access to transcriptional machinery. Epigenetic mechanisms, including histone PTMs and changes in chromatin structure, could help explain neurodegenerative disease processes and illuminate novel treatment targets. Recent research has revealed that changes in histone PTMs and heterochromatin loss or gain are connected to neurodegeneration. Here, we review evidence for epigenetic changes occurring in AD, PD, and FTD/ALS. We focus specifically on alterations in the histone PTMs landscape, changes in the expression of histone modifying enzymes and chromatin remodelers as well as the consequences of these changes in heterochromatin structure. We also highlight the potential for epigenetic therapies in neurodegenerative disease treatment. Given their reversibility and pharmacological accessibility, epigenetic mechanisms provide a promising avenue for novel treatments. Altogether, these findings underscore the need for thorough characterization of epigenetic mechanisms and chromatin structure in neurodegeneration.}, } @article {pmid39345637, year = {2025}, author = {Morgan, KJ and Carley, E and Coyne, AN and Rothstein, JD and Lusk, CP and King, MC}, title = {Visualizing nuclear pore complex plasticity with pan-Expansion Microscopy.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {39345637}, issn = {2692-8205}, support = {F31 HL158119/HL/NHLBI NIH HHS/United States ; R01 GM129308/GM/NIGMS NIH HHS/United States ; R01 NS122236/NS/NINDS NIH HHS/United States ; R21 AR081661/AR/NIAMS NIH HHS/United States ; }, abstract = {The exploration of cell-type and environmentally-responsive nuclear pore complex (NPC) plasticity requires new, accessible tools. Using pan-Expansion Microscopy (pan-ExM), NPCs were identified by machine learning-facilitated segmentation with resolved cytoplasmic rings (CR), inner rings (IR) and nuclear rings (NR). They exhibited a large range of diameters with a bias for dilated NPCs at the basal nuclear surface in clusters suggestive of local islands of nuclear envelope (NE) tension. Whereas hyperosmotic shock constricted NPCs analogously to those found in annulate lamellae (AL), depletion of LINC complexes specifically eliminated the modest nuclear surface diameter biases. Therefore, LINC complexes may contribute locally to nuclear envelope tension to toggle NPC diameter between dilated, but not constricted, states. Lastly, POM121 shifts from the NR to the IR specifically in induced pluripotent stem cell derived neurons (iPSNs) from a patient with C9orf72 amyotrophic lateral sclerosis (ALS). Thus, pan-ExM is a powerful tool to visualize NPC plasticity in physiological and pathological contexts at single NPC resolution.}, } @article {pmid39345438, year = {2024}, author = {Elsayyid, M and Tanis, JE and Yu, Y}, title = {In-cell processing enables rapid and in-depth proteome analysis of low-input Caenorhabditis elegans.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {39345438}, issn = {2692-8205}, support = {P20 GM104316/GM/NIGMS NIH HHS/United States ; R01 GM135433/GM/NIGMS NIH HHS/United States ; T32 GM133395/GM/NIGMS NIH HHS/United States ; }, abstract = {Caenorhabditis elegans is a widely used genetic model organism, however, the worm cuticle complicates extraction of intracellular proteins, a prerequisite for typical bottom-up proteomics. Conventional physical disruption procedures are not only time-consuming, but can also cause significant sample loss, making it difficult to perform proteomics with low-input samples. Here, for the first time, we present an on-filter in-cell (OFIC) processing approach, which can digest C. elegans proteins directly in the cells of the organism after methanol fixation. With OFIC processing and single-shot LCMS analysis, we identified over 9,400 proteins from a sample of only 200 worms, the largest C. elegans proteome reported to date that did not require fractionation or enrichment. We systematically evaluated the performance of the OFIC approach by comparing it with conventional lysis-based methods. Our data suggest equivalent and unbiased performance of OFIC processing for C. elegans proteome identification and quantitation. We further evaluated the OFIC approach with even lower input samples, then used this method to determine how the proteome is impacted by loss of superoxide dismutase sod-1, the ortholog of human SOD-1, a gene associated with amyotrophic lateral sclerosis (ALS). Analysis of 8,800 proteins from only 50 worms as the initial input showed that loss of sod-1 affects the abundance of proteins required for stress response, ribosome biogenesis, and metabolism. In conclusion, our streamlined OFIC approach, which can be broadly applied to other systems, minimizes sample loss while offering the simplest workflow reported to date for C. elegans proteomics analysis.}, } @article {pmid39344431, year = {2025}, author = {Quail, NPA and Leighton, DJ and Newton, J and Davidson, S and Kelly, L and McKeown, A and Chandran, S and Pal, S and Gorrie, GH}, title = {Influences of Specialist Palliative Care Team Input, Advance Care Planning, Non-Invasive Ventilation and Gastrostomy Status on Unscheduled Hospital Admissions and Place of Death for People with Motor Neuron Disease: A Retrospective Cohort Analysis.}, journal = {Journal of palliative care}, volume = {40}, number = {1}, pages = {89-97}, doi = {10.1177/08258597241283179}, pmid = {39344431}, issn = {2369-5293}, mesh = {Humans ; Male ; *Motor Neuron Disease/therapy/mortality ; Female ; *Advance Care Planning/statistics & numerical data ; Retrospective Studies ; Aged ; *Gastrostomy/statistics & numerical data ; Middle Aged ; *Palliative Care/statistics & numerical data ; *Noninvasive Ventilation/statistics & numerical data ; Aged, 80 and over ; Scotland ; Cohort Studies ; Hospitalization/statistics & numerical data ; Terminal Care/statistics & numerical data ; Adult ; }, abstract = {Objective: Motor neuron disease is a rapidly progressing neurological condition. People with life-limiting conditions generally prefer to die at home and avoid hospital admissions, with Specialist Palliative Care Team involvement often pivotal. Our aim was to investigate the role of advance care planning, Specialist Palliative Care Team input and other relevant variables on place of death and unscheduled hospital admissions in a Scottish population of people with motor neuron disease. Methods: National CARE-MND audit data, primary and secondary care data, and local Palliative Care records were interrogated. Chi-square, point-biserial correlation and binary logistic regression analysed associations (p < 0.05 statistically significant). Participants (188) were deceased, having a verified motor neuron disease diagnosis between 2015-2017, diagnosis occurring ≥28 days before death. Results: Advance care planning and Specialist Palliative Care Team input of ≥28 days were associated with increased odds of dying outside hospital (BLR:OR 3.937, CI 1.558-9.948, p = 0.004 and OR 2.657, CI 1.135-6.222, p = 0.024 respectively). Non-invasive ventilation decreased the odds of dying outside hospital (BLR:OR 0.311, CI 0.124-0.781, p = 0.013). Having a gastrostomy increased odds of ≥1 admissions in the last year of life (BLR:OR 5.142, CI 1.715-15.417, p = 0.003). Statistical significance was retained with removal of gastrostomy-related complications. Conclusion: Early Specialist Palliative Care input and advance care planning may increase the likelihood of death outside of hospital for persons with motor neuron disease. Further research is warranted into barriers of facilitating death outside of hospital with home non-invasive ventilation use and the association between gastrostomy status and unscheduled admissions.}, } @article {pmid39344228, year = {2024}, author = {Li, P and Tao, Z and Zhao, X}, title = {The Role of Osteopontin (OPN) in Regulating Microglia Phagocytosis in Nervous System Diseases.}, journal = {Journal of integrative neuroscience}, volume = {23}, number = {9}, pages = {169}, doi = {10.31083/j.jin2309169}, pmid = {39344228}, issn = {0219-6352}, mesh = {*Osteopontin/metabolism/physiology ; *Microglia/metabolism/physiology ; *Phagocytosis/physiology ; Animals ; Humans ; Nervous System Diseases/metabolism ; }, abstract = {Phagocytosis is the process by which certain cells or organelles internalise foreign substances by engulfing them and then digesting or disposing of them. Microglia are the main resident phagocytic cells in the brain. It is generally believed that microglia/macrophages play a role in guiding the brain's repair and functional recovery processes. However, the resident and invading immune cells of the central nervous system can also exacerbate tissue damage by stimulating inflammation and engulfing viable neurons. The functional consequences of microglial phagocytosis remain largely unexplored. Overall, phagocytosis is considered a beneficial phenomenon in acute brain injury because it eliminates dead cells and induces an anti-inflammatory response. Osteopontin (OPN) is a phosphorylated glycoprotein induced by injury in various tissues, including brain tissue. In acute brain injuries such as hemorrhagic stroke and ischemic stroke, OPN is generally believed to have anti-inflammatory effects. OPN can promote the reconstruction of the blood-brain barrier and up-regulate the scavenger receptor CD36. But in chronic diseases such as Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS), OPN can cause microglia to engulf neurons and worsen disease progression. We explored the role of OPN in promoting microglial phagocytosis in nervous system disorders.}, } @article {pmid39344189, year = {2025}, author = {Khorshidi, Z and Adibi, I and Ghasemi, M}, title = {Association between cerebrospinal fluid chitotriosidase level and amyotrophic lateral sclerosis: a systematic review.}, journal = {Hormone molecular biology and clinical investigation}, volume = {46}, number = {1}, pages = {13-19}, pmid = {39344189}, issn = {1868-1891}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/cerebrospinal fluid/diagnosis ; *Hexosaminidases/cerebrospinal fluid ; Biomarkers/cerebrospinal fluid ; }, abstract = {INTRODUCTION: One of the fatal and debilitating neurodegenerative diseases is amyotrophic lateral sclerosis (ALS). Increasing age is one of the risk factors of ALS. Considering that the elderly population in the world is increasing, it is very important to identify useful and effective diagnostic and treatment methods. The purpose of this systematic review is to determine the relationship between chitotriosidase (CHIT1) level and ALS disorder.

CONTENT: Keywords "Amyotrophic Lateral Sclerosis", "Gehrig* Disease", "Charcot Disease", "Guam Disease", ALS, CHIT1 and chitotriosidase were searched in PubMed, Scopus, Web of Science and Science Direct databases without time limit on September 2023. Hundred twenty studies were obtained by searching, and finally, 14 studies were included in this study using the inclusion and exclusion criteria. In all 14 selected studies, the level of biomarker CHIT1 in the CSF of ALS patients was significantly higher than that of healthy control and disease control groups. But, in 8 studies that included 3 groups, no significant difference was observed between the CHIT1 levels in the two control groups. Six studies have reported the amount of CHIT1 level quantitatively. Among these 6 studies, in 5 studies CHIT1 level in disease control was higher than healthy control (not significant) and in only one study CHIT1 level was higher in healthy control compared to disease control (not significant).

SUMMARY AND OUTLOOK: In all 14 studies, a multifold increase in CHIT1 levels has been observed in patients compared to healthy and disease control groups. Therefore, based on the findings of the studies, this study confirms the relationship between CHIT1 increase and ALS disorder.}, } @article {pmid39343990, year = {2024}, author = {Xia, L and Qiu, Y and Li, J and Xu, M and Dong, Z}, title = {The Potential Role of Artemisinins Against Neurodegenerative Diseases.}, journal = {The American journal of Chinese medicine}, volume = {52}, number = {6}, pages = {1641-1660}, doi = {10.1142/S0192415X24500642}, pmid = {39343990}, issn = {1793-6853}, mesh = {Humans ; *Neurodegenerative Diseases/drug therapy ; *Artemisinins/pharmacology ; *Neuroprotective Agents/pharmacology ; Alzheimer Disease/drug therapy/metabolism ; Animals ; Oxidative Stress/drug effects ; Signal Transduction/drug effects ; Parkinson Disease/drug therapy/metabolism ; Ferroptosis/drug effects ; Amyotrophic Lateral Sclerosis/drug therapy ; Huntington Disease/drug therapy/metabolism ; Autophagy/drug effects ; }, abstract = {Artemisinin (ART) and its derivatives, collectively referred to as artemisinins (ARTs), have been approved for the treatment of malaria for decades. ARTs are converted into dihydroartemisinin (DHA), the only active form, which is reductive in vivo. In this review, we provide a brief overview of the neuroprotective potential of ARTs and the underlying mechanisms on several of the most common neurodegenerative diseases, particularly considering their potential application in those associated with cognitive and motor impairments including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS). ARTs act as autophagy balancers to alleviate AD and PD. They inhibit neuroinflammatory responses by regulating phosphorylation of signal transduction proteins, such as AKT, PI3K, ERK, NF-κB, p38 MAPK, IκBα. In addition, ARTs regulate GABAergic signaling in a dose-dependent manner. Although they competitively inhibit the binding of gephyrin to GABAergic receptors, low doses of ARTs enhance GABAergic signaling. ARTs can also inhibit ferroptosis, activate the Akt/Bcl-2, AMPK, or ERK/CREB pathways to reduce oxidative stress, and maintain mitochondrial homeostasis, protecting neurons from oxidative stress injury. More importantly, ARTs structurally combine with and suppress β-Amyloid (A[Formula: see text]-induced neurotoxicity, reduce P-tau, and maintain O-GlcNAcylation/Phosphorylation balance, leading to relieved pathological changes in neurodegenerative diseases. Collectively, these natural properties endow ARTs with unique potential for application in neurodegenerative diseases.}, } @article {pmid39343443, year = {2024}, author = {O'Brien, D and Shaw, PJ}, title = {New developments in the diagnosis and management of motor neuron disease.}, journal = {British medical bulletin}, volume = {152}, number = {1}, pages = {4-15}, doi = {10.1093/bmb/ldae010}, pmid = {39343443}, issn = {1471-8391}, support = {NIHR 203321//NIHR Sheffield Biomedical Research Centre/ ; 972-797//AMBRoSIA Biosampling Programme/ ; 764-780//MNDA (Sheffield Care and Research Centre for Motor Neuron Disorders/ ; }, mesh = {Humans ; *Motor Neuron Disease/therapy/diagnosis ; Neuroprotective Agents/therapeutic use ; Riluzole/therapeutic use ; }, abstract = {INTRODUCTION: Motor neuron disease (MND) is a devastating neurodegenerative disease characterized by progressive muscle weakness.

SOURCES OF DATA: PubMed, MEDLINE, and Cochrane databases were searched for articles to March 2024. Searches involved the terms 'motor neuron disease' or 'amyotrophic lateral sclerosis' and 'epidemiology', 'diagnosis', 'clinical', 'genetic', 'management', 'treatment', or 'trial'.

AREAS OF AGREEMENT: Evidence-based management involves riluzole, multidisciplinary care, provision of noninvasive ventilation and gastrostomy, and symptomatic treatments. Tofersen should be offered to treat SOD1-MND.

AREAS OF CONTROVERSY: Edaravone and Relyvrio are approved treatments in the USA, but insufficient evidence was found to support approval in the UK and Europe.

GROWING POINTS: The discovery of neurofilaments as MND biomarkers, growth of platform trials and development of novel therapies provide optimism for more powerful neuroprotective therapies.

Further work should focus on the elucidation of environmental causes of MND, gene-environment interactions, and advanced cellular models of disease.}, } @article {pmid39342484, year = {2025}, author = {Deneubourg, C and Salimi Dafsari, H and Lowe, S and Martinez-Cotrina, A and Mazaud, D and Park, SH and Vergani, V and Almacellas Barbanoj, A and Maroofian, R and Averdunk, L and Ghayoor-Karimiani, E and Jayawant, S and Mignot, C and Keren, B and Peters, R and Kamath, A and Mattas, L and Verma, S and Silwal, A and Distelmaier, F and Houlden, H and Lignani, G and Antebi, A and Jepson, J and Jungbluth, H and Fanto, M}, title = {Epg5 links proteotoxic stress due to defective autophagic clearance and epileptogenesis in Drosophila and Vici syndrome patients.}, journal = {Autophagy}, volume = {21}, number = {2}, pages = {447-459}, pmid = {39342484}, issn = {1554-8635}, mesh = {Animals ; *Autophagy/genetics ; Humans ; Drosophila melanogaster/metabolism ; *Drosophila Proteins/metabolism/genetics ; *Agenesis of Corpus Callosum/genetics/metabolism/pathology/physiopathology ; *Epilepsy/genetics/metabolism/pathology ; Autophagosomes/metabolism ; Mutation/genetics ; Seizures ; Proteotoxic Stress ; Autophagy-Related Proteins ; Cataract ; Vesicular Transport Proteins ; }, abstract = {Epilepsy is a common neurological condition that arises from dysfunctional neuronal circuit control due to either acquired or innate disorders. Autophagy is an essential neuronal housekeeping mechanism, which causes severe proteotoxic stress when impaired. Autophagy impairment has been associated to epileptogenesis through a variety of molecular mechanisms. Vici Syndrome (VS) is the paradigmatic congenital autophagy disorder in humans due to recessive variants in the ectopic P-granules autophagy tethering factor 5 (EPG5) gene that is crucial for autophagosome-lysosome fusion and autophagic clearance. Here, we used Drosophila melanogaster to study the importance of Epg5 in development, aging, and seizures. Our data indicate that proteotoxic stress due to impaired autophagic clearance and seizure-like behaviors correlate and are commonly regulated, suggesting that seizures occur as a direct consequence of proteotoxic stress and age-dependent neurodegenerative progression. We provide complementary evidence from EPG5-mutated patients demonstrating an epilepsy phenotype consistent with Drosophila predictions.Abbreviations: AD: Alzheimer's disease; ALS-FTD: Amyotrophic Lateral Sclerosis-FrontoTemoporal Dementia; DART: Drosophila Arousal Tracking; ECoG: electrocorticogram; EEG: electroencephalogram; EPG5: ectopic P-granules 5 autophagy tethering factor; KA: kainic acid; MBs: mushroom bodies; MRI magnetic resonance imaging; MTOR: mechanistic target of rapamycin kinase; PD: Parkinson's disease; TSC: TSC complex; VS: Vici syndrome.}, } @article {pmid39341837, year = {2024}, author = {Hollingworth, D and Thomas, F and Page, DA and Fouda, MA and De Castro, RL and Sula, A and Mykhaylyk, VB and Kelly, G and Ulmschneider, MB and Ruben, PC and Wallace, BA}, title = {Structural basis for the rescue of hyperexcitable cells by the amyotrophic lateral sclerosis drug Riluzole.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {8426}, pmid = {39341837}, issn = {2041-1723}, support = {CC1078/WT_/Wellcome Trust/United Kingdom ; BB/105581//RCUK | Biotechnology and Biological Sciences Research Council (BBSRC)/ ; mutiple grants//Diamond Light Source/ ; BB/V0183511//RCUK | Biotechnology and Biological Sciences Research Council (BBSRC)/ ; CF2-100001//Rosetrees Trust/ ; BB/S017844//RCUK | Biotechnology and Biological Sciences Research Council (BBSRC)/ ; studentship//Wellcome Trust (Wellcome)/ ; }, mesh = {*Riluzole/pharmacology ; *Amyotrophic Lateral Sclerosis/drug therapy/metabolism/genetics ; Humans ; *Neuroprotective Agents/pharmacology ; Voltage-Gated Sodium Channels/metabolism/chemistry ; HEK293 Cells ; Animals ; Sodium/metabolism ; Motor Neurons/drug effects/metabolism ; }, abstract = {Neuronal hyperexcitability is a key element of many neurodegenerative disorders including the motor neuron disease Amyotrophic Lateral Sclerosis (ALS), where it occurs associated with elevated late sodium current (INaL). INaL results from incomplete inactivation of voltage-gated sodium channels (VGSCs) after their opening and shapes physiological membrane excitability. However, dysfunctional increases can cause hyperexcitability-associated diseases. Here we reveal the atypical binding mechanism which explains how the neuroprotective ALS-treatment drug riluzole stabilises VGSCs in their inactivated state to cause the suppression of INaL that leads to reversed cellular overexcitability. Riluzole accumulates in the membrane and enters VGSCs through openings to their membrane-accessible fenestrations. Riluzole binds within these fenestrations to stabilise the inactivated channel state, allowing for the selective allosteric inhibition of INaL without the physical block of Na[+] conduction associated with traditional channel pore binding VGSC drugs. We further demonstrate that riluzole can reproduce these effects on a disease variant of the non-neuronal VGSC isoform Nav1.4, where pathologically increased INaL is caused directly by mutation. Overall, we identify a model for VGSC inhibition that produces effects consistent with the inhibitory action of riluzole observed in models of ALS. Our findings will aid future drug design and supports research directed towards riluzole repurposing.}, } @article {pmid39341656, year = {2024}, author = {Paris, A and Lakatos, A}, title = {Cell and gene therapy for amyotrophic lateral sclerosis.}, journal = {Handbook of clinical neurology}, volume = {205}, number = {}, pages = {217-241}, doi = {10.1016/B978-0-323-90120-8.00017-4}, pmid = {39341656}, issn = {0072-9752}, mesh = {*Amyotrophic Lateral Sclerosis/therapy/genetics ; Humans ; *Genetic Therapy/methods ; Animals ; Cell- and Tissue-Based Therapy/methods/trends ; Disease Models, Animal ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal and incurable neurodegenerative disorder with rapidly progressive skeletal muscle weakness, which can also cause a variable cognitive deficit. Genetic causes are only identified in approximately 10% of all cases, with complex genotype-phenotype associations, making it challenging to identify treatment targets. What further hampers therapeutic development is a broad heterogeneity in mechanisms, possible targets, and disturbances across various cell types, aside from the cortical and spinal motor neurons that lie at the heart of the pathology of ALS. Over the last decade, significant progress in biotechnologic techniques, cell and ribonucleic acid (RNA) engineering, animal models, and patient-specific human stem cell and organoid models have accelerated both mechanistic and therapeutic discoveries. The growing number of clinical trials mirrors this. This chapter reviews the current state of human preclinical models supporting trial strategies as well as recent clinical cell and gene therapy approaches.}, } @article {pmid39341507, year = {2024}, author = {Sivalingam, AM}, title = {Advances in understanding biomarkers and treating neurological diseases - Role of the cerebellar dysfunction and emerging therapies.}, journal = {Ageing research reviews}, volume = {101}, number = {}, pages = {102519}, doi = {10.1016/j.arr.2024.102519}, pmid = {39341507}, issn = {1872-9649}, mesh = {Humans ; *Biomarkers/metabolism ; Animals ; *Cerebellar Diseases/therapy/diagnosis/metabolism/genetics ; Genetic Therapy/methods/trends ; Nervous System Diseases/therapy/diagnosis/metabolism ; Cerebellum/metabolism/pathology ; }, abstract = {Cerebellar dysfunction is increasingly recognized as a critical factor in various neurological diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). Research has revealed distinct cerebellar atrophy patterns in conditions such as AD and multiple system atrophy, and studies in mice have highlighted its impact on motor control and cognitive functions. Emerging research into autism spectrum disorder (ASD) has identified key targets, such as elevated levels of chemokine receptors and ZIC family genes. Biomarkers, including cerebrospinal fluid (CSF), genetic markers, and advances in AI and bioinformatics, are enhancing early diagnosis and personalized treatment across neurodegenerative disorders. Notable advancements include improved diagnostic tools, gene therapy, and novel clinical trials. Despite progress, challenges such as the bloodbrain barrier and neuroinflammation persist. Current therapies for AD, PD, HD, and ALS, including antisense oligonucleotides and stem cell treatments, show promise but require further investigation. A comprehensive approach that integrates diagnostic methods and innovative therapies is essential for effective management and improved patient outcomes.}, } @article {pmid39340928, year = {2024}, author = {Dahl, R and Bezprozvanny, I}, title = {SERCA pump as a novel therapeutic target for treating neurodegenerative disorders.}, journal = {Biochemical and biophysical research communications}, volume = {734}, number = {}, pages = {150748}, doi = {10.1016/j.bbrc.2024.150748}, pmid = {39340928}, issn = {1090-2104}, support = {R01 AG071310/AG/NIA NIH HHS/United States ; R56 AG078337/AG/NIA NIH HHS/United States ; R42 AG062001/AG/NIA NIH HHS/United States ; }, mesh = {*Sarcoplasmic Reticulum Calcium-Transporting ATPases/metabolism ; *Neurodegenerative Diseases/drug therapy/metabolism/pathology ; Humans ; Animals ; Disease Models, Animal ; Allosteric Regulation/drug effects ; Molecular Targeted Therapy/methods ; *Neuroprotective Agents/pharmacology/therapeutic use ; Calcium Signaling/drug effects ; Calcium/metabolism ; }, abstract = {The neurodegenerative disorders, such as Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic lateral sclerosis (ALS), Huntington's disease (HD) and Spinocerebellar ataxias (SCAs), present an enormous medical, social, financial and scientific problem. Despite intense research into the causes of these disorders, only marginal progress has been made in the clinic and no cures exist for any of them. Most of the scientific effort has been focused on identification of the major causes of these diseases and on developing ways to target them, such as targeting amyloid accumulation for AD or targeting expression of mutant Huntingtin for HD. Calcium (Ca[2+]) signaling has long been proposed to play an important role in the pathogenesis of neurodegenerative disorders, but blockers of Ca[2+] channels and Ca[2+] signaling proteins have not been translated to clinic primarily due to side effects related to the important roles of target molecules for these compounds at the peripheral tissues. In this review article, we would like to discuss an idea that recently identified positive allosteric modulators (PAMs) of the sarco-endoplasmic reticulum calcium (SERCA) pump may provide a promising approach to develop therapeutic compounds for treatment of these disorders. This hypothesis is supported by the preclinical data obtained with animal models of AD and PD. The first critical test of this idea will be an imminent phase I study that will offer an opportunity to evaluate potential side effects of this class of compounds in humans.}, } @article {pmid39340874, year = {2024}, author = {Xiong, Z and Zeng, Q and Hu, Y and Lai, C and Wu, H}, title = {Optineurin inhibits IBDV replication via interacting with VP1.}, journal = {Veterinary microbiology}, volume = {298}, number = {}, pages = {110261}, doi = {10.1016/j.vetmic.2024.110261}, pmid = {39340874}, issn = {1873-2542}, mesh = {*Virus Replication ; Animals ; *Infectious bursal disease virus/physiology ; *Chickens ; Membrane Transport Proteins/metabolism/genetics ; Cell Cycle Proteins/metabolism/genetics ; Poultry Diseases/virology ; Humans ; Ubiquitination ; Birnaviridae Infections/veterinary/virology ; Cell Line ; Capsid Proteins/metabolism/genetics ; Transcription Factor TFIIIA/metabolism/genetics ; HEK293 Cells ; }, abstract = {Avibirnavirus, specifically Infectious Bursal Disease Virus (IBDV), is a highly contagious pathogen that causes significant economic losses in the poultry industry. The polymerase protein VP1 of IBDV is critical to the viral life cycle, facilitating the synthesis of viral mRNA and the genome. Previous studies have suggested that various host factors influence the regulation of IBDV polymerase activity. In this study, we identified that IBDV infection induces the expression of optineurin (OPTN), a mitophagy receptor and a protein associated with amyotrophic lateral sclerosis (ALS), as well as a negative regulator of interferon I production. The induced expression of OPTN acts as a suppressor of IBDV replication, a function dependent on its ubiquitin-binding domain (UBAN). Furthermore, we demonstrated that OPTN exerts its antiviral effects through direct interactions with VP1 and VP3, which inhibit the polymerase activity of VP1 by preventing K63-linked ubiquitination of VP1. To our knowledge, this study is the first to report that OPTN, upregulated during IBDV infection, functions as a novel antiviral host factor that limits the virus's replicative capacity, offering a potential target for anti-IBDV therapeutic strategies.}, } @article {pmid39340590, year = {2024}, author = {Ghiasvand, K and Amirfazli, M and Moghimi, P and Safari, F and Takhshid, MA}, title = {The role of neuron-like cell lines and primary neuron cell models in unraveling the complexity of neurodegenerative diseases: a comprehensive review.}, journal = {Molecular biology reports}, volume = {51}, number = {1}, pages = {1024}, doi = {10.1007/s11033-024-09964-x}, pmid = {39340590}, issn = {1573-4978}, mesh = {Humans ; *Neurodegenerative Diseases/pathology ; *Neurons/metabolism ; Animals ; Coculture Techniques/methods ; Cell Line ; Models, Biological ; Alzheimer Disease/pathology/genetics ; }, abstract = {Neurodegenerative diseases (NDs) are characterized by the progressive loss of neurons. As to developing effective therapeutic interventions, it is crucial to understand the underlying mechanisms of NDs. Cellular models have become invaluable tools for studying the complex pathogenesis of NDs, offering insights into disease mechanisms, determining potential therapeutic targets, and aiding in drug discovery. This review provides a comprehensive overview of various cellular models used in ND research, focusing on Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. Cell lines, such as SH-SY5Y and PC12 cells, have emerged as valuable tools due to their ease of use, reproducibility, and scalability. Additionally, co-culture models, involving the growth of distinct cell types like neurons and astrocytes together, are highlighted for simulating brain interactions and microenvironment. While cell lines cannot fully replicate the complexity of the human brain, they provide a scalable method for examining important aspects of neurodegenerative diseases. Advancements in cell line technologies, including the incorporation of patient-specific genetic variants and improved co-culture models, hold promise for enhancing our understanding and expediting the development of effective treatments. Integrating multiple cellular models and advanced technologies offers the potential for significant progress in unraveling the intricacies of these debilitating diseases and improving patient outcomes.}, } @article {pmid39340541, year = {2024}, author = {Gagliardi, D and Rizzuti, M and Masrori, P and Saccomanno, D and Del Bo, R and Sali, L and Meneri, M and Scarcella, S and Milone, I and Hersmus, N and Ratti, A and Ticozzi, N and Silani, V and Poesen, K and Van Damme, P and Comi, GP and Corti, S and Verde, F}, title = {Exploiting the role of CSF NfL, CHIT1, and miR-181b as potential diagnostic and prognostic biomarkers for ALS.}, journal = {Journal of neurology}, volume = {271}, number = {12}, pages = {7557-7571}, pmid = {39340541}, issn = {1432-1459}, support = {RF-2018-12366357//Ministero della Salute/ ; RF-2021-12374238//Ministero della Salute/ ; GR-2016-02364373//Ministero della Salute/ ; Ricerca corrente//Ministero della Salute/ ; C1//VIB, KU Leuven/ ; 'Opening the Future' Fund//VIB, KU Leuven/ ; FWO-Vlaanderen//Fund for Scientific Research Flanders/ ; T003519N//TBM grant from FWO-Vlaanderen/ ; G077121N//FWO-Vlaanderen/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/cerebrospinal fluid/diagnosis/genetics ; Female ; Male ; *Neurofilament Proteins/cerebrospinal fluid ; *Biomarkers/cerebrospinal fluid ; Middle Aged ; *Hexosaminidases/cerebrospinal fluid ; Aged ; *MicroRNAs/cerebrospinal fluid ; Prognosis ; Adult ; Cohort Studies ; Disease Progression ; Aged, 80 and over ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a rare neurodegenerative disorder characterized by relentless and progressive loss of motor neurons. A molecular diagnosis, supported by the identification of specific biomarkers, might promote the definition of multiple biological subtypes of ALS, improving patient stratification and providing prognostic information. Here, we investigated the levels of neurofilament light chain (NfL), chitotriosidase (CHIT1) and microRNA-181b (miR-181b) in the cerebrospinal fluid (CSF) of ALS subjects (N = 210) as well as neurologically healthy and neurological disease controls (N = 218, including N = 74 with other neurodegenerative diseases) from a large European multicentric cohort, evaluating their specific or combined utility as diagnostic and prognostic biomarkers. NfL, CHIT1 and miR-181b all showed significantly higher levels in ALS subjects compared to controls, with NfL showing the most effective diagnostic performance. Importantly, all three biomarkers were increased compared to neurodegenerative disease controls and, specifically, to patients with Alzheimer's disease (AD; N = 44), with NfL and CHIT1 being also higher in ALS than in alpha-synucleinopathies (N = 22). Notably, ALS patients displayed increased CHIT1 levels despite having, compared to controls, a higher prevalence of a polymorphism lowering CHIT1 expression. While no relationship was found between CSF miR-181b and clinical measures in ALS (disease duration, functional disability, and disease progression rate), CSF NfL was the best independent predictor of disease progression and survival. This study deepens our knowledge of ALS biomarkers, highlighting the relative specificity of CHIT1 for ALS among neurodegenerative diseases and appraising the potential diagnostic utility of CSF miR-181b.}, } @article {pmid39340452, year = {2024}, author = {Tchounwou, C and Jobanputra, AJ and Lasher, D and Fletcher, BJ and Jacinto, J and Bhaduri, A and Best, RL and Fisher, WS and Ewert, KK and Li, Y and Feinstein, SC and Safinya, CR}, title = {Mixtures of Intrinsically Disordered Neuronal Protein Tau and Anionic Liposomes Reveal Distinct Anionic Liposome-Tau Complexes Coexisting with Tau Liquid-Liquid Phase-Separated Coacervates.}, journal = {Langmuir : the ACS journal of surfaces and colloids}, volume = {40}, number = {40}, pages = {21041-21051}, doi = {10.1021/acs.langmuir.4c02471}, pmid = {39340452}, issn = {1520-5827}, mesh = {*tau Proteins/chemistry/metabolism ; *Liposomes/chemistry ; *Anions/chemistry ; Humans ; Phosphatidylcholines/chemistry ; Phosphatidylserines/chemistry ; Phosphatidylglycerols/chemistry ; Intrinsically Disordered Proteins/chemistry ; }, abstract = {Tau, an intrinsically disordered neuronal protein and polyampholyte with an overall positive charge, is a microtubule (MT) associated protein that binds to anionic domains of MTs and suppresses their dynamic instability. Aberrant tau-MT interactions are implicated in Alzheimer's and other neurodegenerative diseases. Here, we studied the interactions between full-length human protein tau and other negatively charged binding substrates, as revealed by differential interference contrast (DIC) and fluorescence microscopy. As a binding substrate, we chose anionic liposomes (ALs) containing either 1,2-dioleoyl-sn-glycero-3-phosphatidylserine (DOPS, -1e) or 1,2-dioleoyl-sn-glycero-3-phosphatidylglycerol (DOPG, -1e) mixed with zwitterionic 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine (DOPC) to mimic anionic plasma membranes of axons where tau resides. At low salt concentrations (0 to 10 mM KCl or NaCl) with minimal charge screening, reaction mixtures of tau and ALs resulted in the formation of distinct states of AL-tau complexes coexisting with liquid-liquid phase-separated tau self-coacervates arising from the polyampholytic nature of tau containing cationic and anionic domains. AL-tau complexes (i.e. tau-lipoplexes) exhibited distinct types of morphologies. This included large ∼20-30 μm tau-decorated giant vesicles with additional smaller liposomes with bound tau attached to the giant vesicles and tau-mediated finite-size assemblies of small liposomes. As the salt concentration was increased to near and above 150 mM for 1:1 electrolytes, AL-tau complexes remained stable, while tau self-coacervate droplets were found to dissolve, indicative of the breaking of (anionic/cationic) electrostatic bonds between tau chains due to increased charge screening. The findings are consistent with the hypothesis that distinct cationic domains of tau may interact with anionic lipid domains of the lumen-facing monolayer of the axon's plasma membrane, suggesting the possibility of transient yet robust interactions near relevant ionic strengths found in neurons.}, } @article {pmid39340290, year = {2025}, author = {Alves, I and Gromicho, M and Oliveira Santos, M and Pinto, S and de Carvalho, M}, title = {Assessing disease progression in ALS: prognostic subgroups and outliers.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {26}, number = {1-2}, pages = {58-63}, doi = {10.1080/21678421.2024.2407412}, pmid = {39340290}, issn = {2167-9223}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/mortality ; *Disease Progression ; Male ; Female ; Middle Aged ; Prognosis ; Aged ; Adult ; Cohort Studies ; }, abstract = {BACKGROUND: The rate of disease progression, measured by the decline of ALS Functional Rating Scale-Revised (ALSFRS-R) from symptom onset to diagnosis (ΔFS) is a well-established prognostic biomarker for predicting survival. Objectives: This study aims to categorize a large patient cohort based on the initial ΔFS and subsequently investigate survival deviations from the expected prognosis defined by ΔFS.

METHODS: 1056 ALS patients were stratified into three progression categories based on their ΔFS: slow progressors (below 25th percentile), intermediate progressors (between 25th and 75th percentiles), and fast progressors (above 75th percentile). Survival outcomes were classified as short survivors (<2 years), average survivors (2-5 years), and long survivors (>5 years). Clinical and demographic characteristics within each subgroup were then analyzed.

RESULTS: ΔFS stratification yielded cutoff values of <0.29, 0.29-1.03, and >1.03 points/month. Long survivors comprised 26% and 21% were short survivors. Six percent of the fast progressors had a life expectancy of more than 5 years, and none of the clinical and demographic characteristics analyzed could fully explain this discrepancy. Conversely, 13% of intermediate progressors lived less than 2 years, according to a short-diagnostic delay in these patients.

DISCUSSION: Our study reaffirms ΔFS as a prognostic biomarker for ALS. We disclosed outliers defying anticipated patterns. The observed shift in progression categories underscores the non-linear nature of disease progression. Genetic and unknown biological reasons may explain these deviations. Further research is needed to fully understand modulation of ALS survival.}, } @article {pmid39338620, year = {2024}, author = {Razzaq, Z and Brahimi, N and Rehman, HZU and Khan, ZH}, title = {Intelligent Control System for Brain-Controlled Mobile Robot Using Self-Learning Neuro-Fuzzy Approach.}, journal = {Sensors (Basel, Switzerland)}, volume = {24}, number = {18}, pages = {}, pmid = {39338620}, issn = {1424-8220}, mesh = {*Fuzzy Logic ; *Robotics/methods ; Humans ; *Brain-Computer Interfaces ; *Electroencephalography/methods ; Algorithms ; Brain/physiology ; Neural Networks, Computer ; Machine Learning ; }, abstract = {Brain-computer interface (BCI) provides direct communication and control between the human brain and physical devices. It is achieved by converting EEG signals into control commands. Such interfaces have significantly improved the lives of disabled individuals suffering from neurological disorders-such as stroke, amyotrophic lateral sclerosis (ALS), and spinal cord injury-by extending their movement range and thereby promoting self-independence. Brain-controlled mobile robots, however, often face challenges in safety and control performance due to the inherent limitations of BCIs. This paper proposes a shared control scheme for brain-controlled mobile robots by utilizing fuzzy logic to enhance safety, control performance, and robustness. The proposed scheme is developed by combining a self-learning neuro-fuzzy (SLNF) controller with an obstacle avoidance controller (OAC). The SLNF controller robustly tracks the user's intentions, and the OAC ensures the safety of the mobile robot following the BCI commands. Furthermore, SLNF is a model-free controller that can learn as well as update its parameters online, diminishing the effect of disturbances. The experimental results prove the efficacy and robustness of the proposed SLNF controller including a higher task completion rate of 94.29% (compared to 79.29%, and 92.86% for Direct BCI and Fuzzy-PID, respectively), a shorter average task completion time of 85.31 s (compared to 92.01 s and 86.16 s for Direct BCI and Fuzzy-PID, respectively), and reduced settling time and overshoot.}, } @article {pmid39338563, year = {2024}, author = {Dow, CT and Pierce, ES and Sechi, LA}, title = {Mycobacterium paratuberculosis: A HERV Turn-On for Autoimmunity, Neurodegeneration, and Cancer?.}, journal = {Microorganisms}, volume = {12}, number = {9}, pages = {}, pmid = {39338563}, issn = {2076-2607}, abstract = {Human endogenous retroviruses (HERVs) are remnants of ancient retroviral infections that, over millions of years, became integrated into the human genome. While normally inactive, environmental stimuli such as infections have contributed to the transcriptional reactivation of HERV-promoting pathological conditions, including the development of autoimmunity, neurodegenerative disease and cancer. What infections trigger HERV activation? Mycobacterium avium subspecies paratuberculosis (MAP) is a pluripotent driver of human disease. Aside from granulomatous diseases, Crohn's disease, sarcoidosis and Blau syndrome, MAP is associated with autoimmune disease: type one diabetes (T1D), multiple sclerosis (MS), rheumatoid arthritis (RA) and autoimmune thyroiditis. MAP is also associated with Alzheimer's disease (AD) and Parkinson's disease (PD). Autoimmune diabetes, MS and RA are the diseases with the strongest MAP/HERV association. There are several other diseases associated with HERV activation, including diseases whose epidemiology and/or pathology would prompt speculation for a causal role of MAP. These include non-solar uveal melanoma, colon cancer, glioblastoma and amyotrophic lateral sclerosis (ALS). This article further points to MAP infection as a contributor to autoimmunity, neurodegenerative disease and cancer via the un-silencing of HERV. We examine the link between the ever-increasing number of MAP-associated diseases and the MAP/HERV intersection with these diverse medical conditions, and propose treatment opportunities based upon this association.}, } @article {pmid39337908, year = {2024}, author = {Wang, R and Chen, L and Zhang, Y and Sun, B and Liang, M}, title = {Expression Changes of miRNAs in Humans and Animal Models of Amyotrophic Lateral Sclerosis and Their Potential Application for Clinical Diagnosis.}, journal = {Life (Basel, Switzerland)}, volume = {14}, number = {9}, pages = {}, pmid = {39337908}, issn = {2075-1729}, support = {YJXJ-JZ-2021-0014//Scientific Research Project of Beijing Yicheng Cooperative Development Foundation in 2021-Public welfare projects of rare disease related topics/ ; KM202310858001//R&D Program of Beijing Municipal Education Commission/ ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a severe motor neuron disease. Current detection methods can only confirm the diagnosis at the onset of the disease, missing the critical window for early treatment. Recent studies using animal models have found that detecting changes in miRNA sites can predict the onset and severity of the disease in its early stages, facilitating early diagnosis and treatment. miRNAs show expression changes in motor neurons that connect the brain, spinal cord, and brain stem, as well as in the skeletal muscle in mouse models of ALS. Clinically, expression changes in some miRNAs in patients align with those in mouse models, such as the upregulation of miR-29b in the brain and the upregulation of miR-206 in the skeletal muscle. This study provides an overview of some miRNA study findings in humans as well as in animal models, including SOD1, FUS, TDP-43, and C9orf72 transgenic mice and wobbler mice, highlighting the potential of miRNAs as diagnostic markers for ALS. miR-21 and miR-206 are aberrantly expressed in both mouse model and patient samples, positioning them as key potential diagnostic markers in ALS. Additionally, miR-29a, miR-29b, miR-181a, and miR-142-3p have shown aberrant expression in both types of samples and show promise as clinical targets for ALS. Finally, miR-1197 and miR-486b-5p have been recently identified as aberrantly expressed miRNAs in mouse models for ALS, although further studies are needed to determine their viability as diagnostic targets.}, } @article {pmid39337696, year = {2024}, author = {Niazi, SK}, title = {Bioavailability as Proof to Authorize the Clinical Testing of Neurodegenerative Drugs-Protocols and Advice for the FDA to Meet the ALS Act Vision.}, journal = {International journal of molecular sciences}, volume = {25}, number = {18}, pages = {}, pmid = {39337696}, issn = {1422-0067}, mesh = {Humans ; *United States Food and Drug Administration ; United States ; *Drug Approval ; *Biological Availability ; *Amyotrophic Lateral Sclerosis/drug therapy ; Neurodegenerative Diseases/drug therapy ; Blood-Brain Barrier/metabolism ; Clinical Trials as Topic ; }, abstract = {Although decades of intensive drug discovery efforts to treat neurodegenerative disorders (NDs) have failed, around half a million patients in more than 2000 studies continue being tested, costing over USD 100 billion, despite the conclusion that even those drugs which have been approved have no better effect than a placebo. The US Food and Drug Administration (FDA) has established multiple programs to innovate the treatment of rare diseases, particularly NDs, providing millions of USD in funding primarily by encouraging novel clinical trials to account for issues related to study sizes and adopting multi-arm studies to account for patient dropouts. Instead, the FDA should focus on the primary reason for failure: the poor bioavailability of drugs reaching the brain (generally 0.1% at most) due to the blood-brain barrier (BBB). There are several solutions to enhance entry into the brain, and the FDA must require proof of significant entry into the brain as the prerequisite to approving Investigational New Drug (IND) applications. The FDA should also rely on factors other than biomarkers to confirm efficacy, as these are rarely relevant to clinical use. This study summarizes how the drugs used to treat NDs can be made effective and how the FDA should change its guidelines for IND approval of these drugs.}, } @article {pmid39337560, year = {2024}, author = {Malaguarnera, M and Cabrera-Pastor, A}, title = {Emerging Role of Extracellular Vesicles as Biomarkers in Neurodegenerative Diseases and Their Clinical and Therapeutic Potential in Central Nervous System Pathologies.}, journal = {International journal of molecular sciences}, volume = {25}, number = {18}, pages = {}, pmid = {39337560}, issn = {1422-0067}, support = {PI23/00204//Instituto de Salud Carlos III (ISCIII) through the project "PI23/00204" and co-funded by the European Union; and Conselleria de Educación/Innovación, Universidades, Ciencia y Sociedad Digital, subvenciones para la realización de proyectos de I+D+i desarro/ ; CIGE/083//This research was funded by Instituto de Salud Carlos III (ISCIII) through the project "PI23/00204" and co-funded by the European Union; and Conselleria de Educación/Innovación, Universidades, Ciencia y Sociedad Digital, subvenciones para la realización d/ ; }, mesh = {Humans ; *Extracellular Vesicles/metabolism ; *Biomarkers/metabolism ; *Neurodegenerative Diseases/therapy/metabolism/diagnosis ; Animals ; Central Nervous System Diseases/metabolism/therapy/diagnosis ; Blood-Brain Barrier/metabolism ; }, abstract = {The emerging role of extracellular vesicles (EVs) in central nervous system (CNS) diseases is gaining significant interest, particularly their applications as diagnostic biomarkers and therapeutic agents. EVs are involved in intercellular communication and are secreted by all cell types. They contain specific markers and a diverse cargo such as proteins, lipids, and nucleic acids, reflecting the physiological and pathological state of their originating cells. Their reduced immunogenicity and ability to cross the blood-brain barrier make them promising candidates for both biomarkers and therapeutic agents. In the context of CNS diseases, EVs have shown promise as biomarkers isolable from different body fluids, providing a non-invasive method for diagnosing CNS diseases and monitoring disease progression. This makes them useful for the early detection and monitoring of diseases such as Alzheimer's, Parkinson's, and amyotrophic lateral sclerosis, where specific alterations in EVs content can be detected. Additionally, EVs derived from stem cells show potential in promoting tissue regeneration and repairing damaged tissues. An evaluation has been conducted on the current clinical trials studying EVs for CNS diseases, focusing on their application, treatment protocols, and obtained results. This review aims to explore the potential of EVs as diagnostic markers and therapeutic carriers for CNS diseases, highlighting their significant advantages and ongoing clinical trials evaluating their efficacy.}, } @article {pmid39337454, year = {2024}, author = {Rizea, RE and Corlatescu, AD and Costin, HP and Dumitru, A and Ciurea, AV}, title = {Understanding Amyotrophic Lateral Sclerosis: Pathophysiology, Diagnosis, and Therapeutic Advances.}, journal = {International journal of molecular sciences}, volume = {25}, number = {18}, pages = {}, pmid = {39337454}, issn = {1422-0067}, mesh = {*Amyotrophic Lateral Sclerosis/therapy/diagnosis/physiopathology/metabolism/genetics ; Humans ; Biomarkers ; Genetic Therapy/methods ; Oxidative Stress ; Animals ; Mitochondria/metabolism ; }, abstract = {This review offers an in-depth examination of amyotrophic lateral sclerosis (ALS), addressing its epidemiology, pathophysiology, clinical presentation, diagnostic techniques, and current as well as emerging treatments. The purpose is to condense key findings and illustrate the complexity of ALS, which is shaped by both genetic and environmental influences. We reviewed the literature to discuss recent advancements in understanding molecular mechanisms such as protein misfolding, mitochondrial dysfunction, oxidative stress, and axonal transport defects, which are critical for identifying potential therapeutic targets. Significant progress has been made in refining diagnostic criteria and identifying biomarkers, leading to earlier and more precise diagnoses. Although current drug treatments provide some benefits, there is a clear need for more effective therapies. Emerging treatments, such as gene therapy and stem cell therapy, show potential in modifying disease progression and improving the quality of life for ALS patients. The review emphasizes the importance of continued research to address challenges such as disease variability and the limited effectiveness of existing treatments. Future research should concentrate on further exploring the molecular foundations of ALS and developing new therapeutic approaches. The implications for clinical practice include ensuring the accessibility of new treatments and that healthcare systems are equipped to support ongoing research and patient care.}, } @article {pmid39337436, year = {2024}, author = {Guo, D and Liu, Z and Zhou, J and Ke, C and Li, D}, title = {Significance of Programmed Cell Death Pathways in Neurodegenerative Diseases.}, journal = {International journal of molecular sciences}, volume = {25}, number = {18}, pages = {}, pmid = {39337436}, issn = {1422-0067}, support = {2023Y9415//Joint Funds for the innovation of science and Technology, Fujian province/ ; }, mesh = {Humans ; *Neurodegenerative Diseases/metabolism/pathology ; *Signal Transduction ; Animals ; *Apoptosis ; Ferroptosis ; Neurons/metabolism/pathology ; }, abstract = {Programmed cell death (PCD) is a form of cell death distinct from accidental cell death (ACD) and is also referred to as regulated cell death (RCD). Typically, PCD signaling events are precisely regulated by various biomolecules in both spatial and temporal contexts to promote neuronal development, establish neural architecture, and shape the central nervous system (CNS), although the role of PCD extends beyond the CNS. Abnormalities in PCD signaling cascades contribute to the irreversible loss of neuronal cells and function, leading to the onset and progression of neurodegenerative diseases. In this review, we summarize the molecular processes and features of different modalities of PCD, including apoptosis, necroptosis, pyroptosis, ferroptosis, cuproptosis, and other novel forms of PCD, and their effects on the pathogenesis of neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), spinal muscular atrophy (SMA), multiple sclerosis (MS), traumatic brain injury (TBI), and stroke. Additionally, we examine the key factors involved in these PCD signaling pathways and discuss the potential for their development as therapeutic targets and strategies. Therefore, therapeutic strategies targeting the inhibition or facilitation of PCD signaling pathways offer a promising approach for clinical applications in treating neurodegenerative diseases.}, } @article {pmid39337251, year = {2024}, author = {Escudier, O and Zhang, Y and Whiting, A and Chazot, P}, title = {Evaluation of a Synthetic Retinoid, Ellorarxine, in the NSC-34 Cell Model of Motor Neuron Disease.}, journal = {International journal of molecular sciences}, volume = {25}, number = {18}, pages = {}, pmid = {39337251}, issn = {1422-0067}, mesh = {Animals ; Mice ; *Neuroprotective Agents/pharmacology ; Retinoids/pharmacology ; Amyotrophic Lateral Sclerosis/drug therapy/metabolism/pathology ; Cell Line ; Humans ; Receptors, AMPA/metabolism ; Motor Neurons/drug effects/metabolism/pathology ; Benzoates/pharmacology ; Motor Neuron Disease/drug therapy/metabolism/pathology ; Calcium/metabolism ; Neurites/drug effects/metabolism ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disease worldwide and is characterized by progressive muscle atrophy. There are currently two approved treatments, but they only relieve symptoms briefly and do not cure the disease. The main hindrance to research is the complex cause of ALS, with its pathogenesis not yet fully elucidated. Retinoids (vitamin A derivatives) appear to be essential in neuronal cells and have been implicated in ALS pathogenesis. This study explores 4-[2-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydroquinoxalin-2-yl)ethylnyl]benzoic acid (Ellorarxine, or DC645 or NVG0645), a leading synthetic retinoic acid, discussing its pharmacological mechanisms, neuroprotective properties, and relevance to ALS. The potential therapeutic effect of Ellorarxine was analyzed in vitro using the WT and SOD1G93A NSC-34 cell model of ALS at an administered concentration of 0.3-30 nM. Histological, functional, and biochemical analyses were performed. Elorarxine significantly increased MAP2 expression and neurite length, increased AMPA receptor GluA2 expression and raised intracellular Ca[2+] baseline, increased level of excitability, and reduced Ca[2+] spike during depolarization in neurites. Ellorarxine also displayed both antioxidant and anti-inflammatory effects. Overall, these results suggest Ellorarxine shows relevance and promise as a novel therapeutic strategy for treatment of ALS.}, } @article {pmid39336788, year = {2024}, author = {Tourtourikov, I and Todorov, T and Angelov, T and Chamova, T and Tournev, I and Mitev, V and Todorova, A}, title = {Genetic Modifiers of ALS: The Impact of Chromogranin B P413L in a Bulgarian ALS Cohort.}, journal = {Genes}, volume = {15}, number = {9}, pages = {}, pmid = {39336788}, issn = {2073-4425}, support = {Grant No. D-148/ 03.08.2023//Medical University of Sofia/ ; National Recovery and Resilience Plan of the Republic of Bulgaria, project № BG-RRP-2.004-0004-C01//European Union-NextGenerationEU/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics ; Male ; Female ; Bulgaria ; Middle Aged ; Aged ; Adult ; *Genetic Predisposition to Disease ; *Chromogranin B/genetics ; Age of Onset ; Alleles ; Genotype ; Polymorphism, Single Nucleotide ; Cohort Studies ; Gene Frequency ; Kaplan-Meier Estimate ; }, abstract = {This study investigated the role of the CHGB P413L variant (rs742710) in sporadic amyotrophic lateral sclerosis (sALS) within the Bulgarian population. We analyzed 150 patients with sALS (85 male and 65 female) for the presence of this variant, its potential impact on disease susceptibility, and age of onset. Genotyping was performed using PCR amplification and direct Sanger sequencing. Statistical analyses included comparisons with control data from GnomAD v2.1.1, one-way ANOVA, and Kaplan-Meier survival analysis. Results revealed a higher frequency of the minor T allele in patients with sALS compared to all control groups and a statistically significant increase in carrier genotypes compared to non-Finnish Europeans (χ[2] = 15.4572, p = 0.000440). However, the impact on age of onset was less clear, with no statistically significant differences observed across genotypes or between carriers and non-carriers of the T allele. Kaplan-Meier analysis suggested a potential 2.5-year-earlier onset in T allele carriers, but the small sample size of carriers limits the reliability of this finding. Our study provides evidence for an association between the CHGB P413L variant and sALS susceptibility in the Bulgarian population, while its effect on age of onset remains uncertain, highlighting the need for further research in larger, diverse cohorts.}, } @article {pmid39336748, year = {2024}, author = {Chami, AA and Bedja-Iacona, L and Richard, E and Lanznaster, D and Marouillat, S and Veyrat-Durebex, C and Andres, CR and Corcia, P and Blasco, H and Vourc'h, P}, title = {N-Terminal Fragments of TDP-43-In Vitro Analysis and Implication in the Pathophysiology of Amyotrophic Lateral Sclerosis and Frontotemporal Lobar Degeneration.}, journal = {Genes}, volume = {15}, number = {9}, pages = {}, pmid = {39336748}, issn = {2073-4425}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology ; *Frontotemporal Lobar Degeneration/genetics/metabolism/pathology ; *DNA-Binding Proteins/genetics/metabolism ; HEK293 Cells ; Protein Domains ; Cell Survival/genetics ; }, abstract = {Abnormal cytoplasmic aggregates containing the TDP-43 protein and its fragments are present in the central nervous system of the majority of patients with amyotrophic lateral sclerosis (ALS) and in patients with frontotemporal lobar degeneration (FTLD). Many studies have focused on the C-terminal cleavage products of TDP-43 (CTFs), but few have focused on the N-terminal products (NTFs), yet several works and their protein domain composition support the involvement of NTFs in pathophysiology. In the present study, we expressed six NTFs of TDP-43, normally generated in vivo by proteases or following the presence of pathogenic genetic truncating variants, in HEK-293T cells. The N-terminal domain (NTD) alone was not sufficient to produce aggregates. Fragments containing the NTD and all or part of the RRM1 domain produced nuclear aggregates without affecting cell viability. Only large fragments also containing the RRM2 domain, with or without the glycine-rich domain, produced cytoplasmic aggregates. Of these, only NTFs containing even a very short portion of the glycine-rich domain caused a reduction in cell viability. Our results provide insights into the involvement of different TDP-43 domains in the formation of nuclear or cytoplasmic aggregates and support the idea that work on the development of therapeutic molecules targeting TDP-43 must also take into account NTFs and, in particular, those containing even a small part of the glycine-rich domain.}, } @article {pmid39336146, year = {2024}, author = {Duranti, E and Villa, C}, title = {From Brain to Muscle: The Role of Muscle Tissue in Neurodegenerative Disorders.}, journal = {Biology}, volume = {13}, number = {9}, pages = {}, pmid = {39336146}, issn = {2079-7737}, abstract = {Neurodegenerative diseases (NDs), like amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), and Parkinson's disease (PD), primarily affect the central nervous system, leading to progressive neuronal loss and motor and cognitive dysfunction. However, recent studies have revealed that muscle tissue also plays a significant role in these diseases. ALS is characterized by severe muscle wasting as a result of motor neuron degeneration, as well as alterations in gene expression, protein aggregation, and oxidative stress. Muscle atrophy and mitochondrial dysfunction are also observed in AD, which may exacerbate cognitive decline due to systemic metabolic dysregulation. PD patients exhibit muscle fiber atrophy, altered muscle composition, and α-synuclein aggregation within muscle cells, contributing to motor symptoms and disease progression. Systemic inflammation and impaired protein degradation pathways are common among these disorders, highlighting muscle tissue as a key player in disease progression. Understanding these muscle-related changes offers potential therapeutic avenues, such as targeting mitochondrial function, reducing inflammation, and promoting muscle regeneration with exercise and pharmacological interventions. This review emphasizes the importance of considering an integrative approach to neurodegenerative disease research, considering both central and peripheral pathological mechanisms, in order to develop more effective treatments and improve patient outcomes.}, } @article {pmid39335997, year = {2024}, author = {Dork, J and Mangan, E and Burns, L and Dimenstein, E}, title = {Affective Instability: Impact of Fluctuating Emotions on Regulation and Psychological Well-Being.}, journal = {Behavioral sciences (Basel, Switzerland)}, volume = {14}, number = {9}, pages = {}, pmid = {39335997}, issn = {2076-328X}, abstract = {Previous research has focused on understanding the occurrence of intense and fluctuating emotions and the ability to manage these emotions and affective states. These phenomena have been, respectively, labeled as affective instability and emotion regulation and have been studied among individuals diagnosed with borderline personality disorder (BPD), attention-deficit/hyperactivity disorder (ADHD), bipolar disorder (BD), and post-traumatic stress disorder (PTSD). Previous findings suggest that affective instability may be associated with poorer psychological well-being. The present study aims to investigate the general tendency of affective instability and capacity for emotional regulation among college students, regardless of a previous psychological diagnosis, and to understand the relationship between these processes and psychological well-being. Three questionnaires were administered to measure levels of affective instability, the ability to manage fluctuating affective states, and overall psychological well-being. The findings suggest that (1) individuals with diagnoses experience affective lability and difficulty regulating emotions at a greater rate than those without, (2) higher affective lability scores are consistent with more significant emotion dysregulation and lower overall psychological well-being, and (3) scores on the Affective lability Scale (ALS) and the Difficulties in Emotional Regulation Scale (DERS) are reliable predictors of one's estimated Global Assessment of Functioning (GAF) scores. Although causation has not been established, the evidence suggests that individuals with diagnoses experience greater difficulty in regulating their emotions, have greater affective lability, and experience diminished psychological well-being and day-to-day functionality. Certain anecdotal evidence suggests that emotional lability can be endogenous and affect multiple aspects of an individual's social, occupational, and personal life. By revising the existing literature and the present findings, the authors provide insights into the significance of endogenous factors in the context of affective lability and offer suggestions for future research.}, } @article {pmid39335582, year = {2024}, author = {Carata, E and Muci, M and Mariano, S and Panzarini, E}, title = {BV2 Microglial Cell Activation/Polarization Is Influenced by Extracellular Vesicles Released from Mutated SOD1 NSC-34 Motoneuron-like Cells.}, journal = {Biomedicines}, volume = {12}, number = {9}, pages = {}, pmid = {39335582}, issn = {2227-9059}, abstract = {Microglia-mediated neuroinflammation is a key player in the pathogenesis of amyotrophic lateral sclerosis (ALS) as it can contribute to the progressive degeneration of motor neurons (MNs). Here, we investigated the role of mSOD1 NSC-34 MN-like cell-derived extracellular vesicles (EVs) in inducing the activation of BV2 microglial cells. NSC-34-released EVs were isolated by culture medium differential ultracentrifugation to obtain two fractions, one containing small EVs (diameter < 200 nm) and the other containing large EVs (diameter > 200 nm). BV2 cells were incubated with the two EV fractions for 12, 24, and 48 h to evaluate 1) the state of microglial inflammation through RT-PCR of IL-1β, IL-6, IL-4, and IL-10 and 2) the expression of proteins involved in inflammasome activation (IL-β and caspase 1), cell death (caspase 3), and glial cell recruitment (CXCR1), and presence of the TGFβ cytokine receptor (TGFβ-R2). The obtained results suggest a mSOD1 type-dependent polarization of BV2 cells towards an early neurotoxic phenotype and a late neuroprotective status, with an appearance of mixed M1 and M2 microglia subpopulations. A significant role in driving microglial cell activation is played by the TGFβ/CX3CR1 axis. Therefore, targeting the dysregulated microglial response and modulating neuroinflammation could hold promise as a therapeutic strategy for ALS.}, } @article {pmid39335395, year = {2024}, author = {Ore, A and Angelastro, JM and Giulivi, C}, title = {Integrating Mitochondrial Biology into Innovative Cell Therapies for Neurodegenerative Diseases.}, journal = {Brain sciences}, volume = {14}, number = {9}, pages = {}, pmid = {39335395}, issn = {2076-3425}, support = {R21 NS128751/NS/NINDS NIH HHS/United States ; }, abstract = {The role of mitochondria in neurodegenerative diseases is crucial, and recent developments have highlighted its significance in cell therapy. Mitochondrial dysfunction has been implicated in various neurodegenerative disorders, including Alzheimer's, Parkinson's, amyotrophic lateral sclerosis, and Huntington's diseases. Understanding the impact of mitochondrial biology on these conditions can provide valuable insights for developing targeted cell therapies. This mini-review refocuses on mitochondria and emphasizes the potential of therapies leveraging mesenchymal stem cells, embryonic stem cells, induced pluripotent stem cells, stem cell-derived secretions, and extracellular vesicles. Mesenchymal stem cell-mediated mitochondria transfer is highlighted for restoring mitochondrial health in cells with dysfunctional mitochondria. Additionally, attention is paid to gene-editing techniques such as mito-CRISPR, mitoTALENs, mito-ZNFs, and DdCBEs to ensure the safety and efficacy of stem cell treatments. Challenges and future directions are also discussed, including the possible tumorigenic effects of stem cells, off-target effects, disease targeting, immune rejection, and ethical issues.}, } @article {pmid39334855, year = {2024}, author = {Hasan, A and Staveley, BE}, title = {Bcl-2 Orthologues, Buffy and Debcl, Can Suppress Drp1-Dependent Age-Related Phenotypes in Drosophila.}, journal = {Biomolecules}, volume = {14}, number = {9}, pages = {}, pmid = {39334855}, issn = {2218-273X}, support = {RGPIN-2016-04828//Natural Sciences and Engineering Research Council/ ; }, mesh = {Animals ; *Aging/genetics/metabolism ; Cytoskeletal Proteins ; *Drosophila melanogaster/genetics/metabolism ; *Drosophila Proteins/metabolism/genetics ; Dynamins/genetics/metabolism ; GTP-Binding Proteins ; Longevity/genetics ; Mitochondrial Proteins/genetics/metabolism ; Phenotype ; *Proto-Oncogene Proteins c-bcl-2/metabolism/genetics ; *Membrane Proteins/metabolism ; }, abstract = {The relationship of Amyotrophic Lateral Sclerosis, Parkinson's disease, and other age-related neurodegenerative diseases with mitochondrial dysfunction has led to our study of the mitochondrial fission gene Drp1 in Drosophila melanogaster and aspects of aging. Previously, the Drp1 protein has been demonstrated to interact with the Drosophila Bcl-2 mitochondrial proteins, and Drp1 mutations can lead to mitochondrial dysfunction and neuronal loss. In this study, the Dopa decarboxylase-Gal4 (Ddc-Gal4) transgene was exploited to direct the expression of Drp1 and Drp1-RNAi transgenes in select neurons. Here, the knockdown of Drp1 seems to compromise locomotor function throughout life but does not alter longevity. The co-expression of Buffy suppresses the poor climbing induced by the knockdown of the Drp1 function. The consequences of Drp1 overexpression, which specifically reduced median lifespan and diminished climbing abilities over time, can be suppressed through the directed co-overexpression of pro-survival Bcl-2 gene Buffy or by the co-knockdown of the pro-cell death Bcl-2 homologue Debcl. Alteration of the expression of Drp1 acts to phenocopy neurodegenerative disease phenotypes in Drosophila, while overexpression of Buffy can counteract or rescue these phenotypes to improve overall health. The diminished healthy aging due to either the overexpression of Drp1 or the RNA interference of Drp1 has produced novel Drosophila models for investigating mechanisms underlying neurodegenerative disease.}, } @article {pmid39334843, year = {2024}, author = {Lucchi, C and Simonini, C and Rustichelli, C and Avallone, R and Zucchi, E and Martinelli, I and Biagini, G and Mandrioli, J}, title = {Reduced Levels of Neurosteroids in Cerebrospinal Fluid of Amyotrophic Lateral Sclerosis Patients.}, journal = {Biomolecules}, volume = {14}, number = {9}, pages = {}, pmid = {39334843}, issn = {2218-273X}, support = {Ricerca Finalizzata bando 2021 (RF-2021-12373036)//Ministero della Salute/ ; bando FAR 2021, Progetti di ricerca Interdisciplinari Mission Oriented, NEURALS project//University of Modena and Reggio Emilia/ ; Neurobiobanca di Modena//Fondazione Cassa di Risparmio di Modena/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/cerebrospinal fluid ; Humans ; Middle Aged ; Male ; Female ; *Neurosteroids/cerebrospinal fluid ; Case-Control Studies ; Aged ; Biomarkers/cerebrospinal fluid ; Pregnanolone/cerebrospinal fluid ; Adult ; Pregnenolone/cerebrospinal fluid ; Progesterone/cerebrospinal fluid ; Testosterone/cerebrospinal fluid ; Chromatography, Liquid ; Tandem Mass Spectrometry ; }, abstract = {Produced by the mitochondria and endoplasmic reticulum, neurosteroids such as allopregnanolone are neuroprotective molecules that influence various neuronal functions and regulate neuroinflammation. They are reduced in neurodegenerative diseases, while in the Wobbler mouse model, allopregnanolone and its precursor progesterone showed protective effects on motor neuron degeneration. This single-center case-control study included 37 patients with amyotrophic lateral sclerosis (ALS) and 28 healthy controls. Cerebrospinal fluid (CSF) neurosteroid levels were quantified using liquid chromatography-electrospray tandem mass spectrometry and compared between the two cohorts. Neurosteroid concentrations have been correlated with neuroinflammation and neurodegeneration biomarkers detected through an automated immunoassay, along with disease features and progression. Pregnenolone, progesterone, allopregnanolone, pregnanolone, and testosterone levels were significantly lower in ALS patients' CSF compared to healthy controls. A significant inverse correlation was found between neurofilament and neurosteroid levels. Neurosteroid concentrations did not correlate with disease progression, phenotype, genotype, or survival prediction. Our study suggests the independence of the disease features and its progression, from the dysregulation of neurosteroids in ALS patients' CSF. This neurosteroid reduction may relate to disease pathogenesis or be a consequence of disease-related processes, warranting further research. The inverse correlation between neurosteroids and neurofilament levels may indicate a failure of compensatory neuroprotective mechanisms against neurodegeneration.}, } @article {pmid39334720, year = {2024}, author = {Munteanu, C and Galaction, AI and Turnea, M and Blendea, CD and Rotariu, M and Poștaru, M}, title = {Redox Homeostasis, Gut Microbiota, and Epigenetics in Neurodegenerative Diseases: A Systematic Review.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {13}, number = {9}, pages = {}, pmid = {39334720}, issn = {2076-3921}, abstract = {Neurodegenerative diseases encompass a spectrum of disorders marked by the progressive degeneration of the structure and function of the nervous system. These conditions, including Parkinson's disease (PD), Alzheimer's disease (AD), Huntington's disease (HD), Amyotrophic lateral sclerosis (ALS), and Multiple sclerosis (MS), often lead to severe cognitive and motor deficits. A critical component of neurodegenerative disease pathologies is the imbalance between pro-oxidant and antioxidant mechanisms, culminating in oxidative stress. The brain's high oxygen consumption and lipid-rich environment make it particularly vulnerable to oxidative damage. Pro-oxidants such as reactive nitrogen species (RNS) and reactive oxygen species (ROS) are continuously generated during normal metabolism, counteracted by enzymatic and non-enzymatic antioxidant defenses. In neurodegenerative diseases, this balance is disrupted, leading to neuronal damage. This systematic review explores the roles of oxidative stress, gut microbiota, and epigenetic modifications in neurodegenerative diseases, aiming to elucidate the interplay between these factors and identify potential therapeutic strategies. We conducted a comprehensive search of articles published in 2024 across major databases, focusing on studies examining the relationships between redox homeostasis, gut microbiota, and epigenetic changes in neurodegeneration. A total of 161 studies were included, comprising clinical trials, observational studies, and experimental research. Our findings reveal that oxidative stress plays a central role in the pathogenesis of neurodegenerative diseases, with gut microbiota composition and epigenetic modifications significantly influencing redox balance. Specific bacterial taxa and epigenetic markers were identified as potential modulators of oxidative stress, suggesting novel avenues for therapeutic intervention. Moreover, recent evidence from human and animal studies supports the emerging concept of targeting redox homeostasis through microbiota and epigenetic therapies. Future research should focus on validating these targets in clinical settings and exploring the potential for personalized medicine strategies based on individual microbiota and epigenetic profiles.}, } @article {pmid39333504, year = {2024}, author = {Cozzi, M and Magri, S and Tedesco, B and Patelli, G and Ferrari, V and Casarotto, E and Chierichetti, M and Pramaggiore, P and Cornaggia, L and Piccolella, M and Galbiati, M and Rusmini, P and Crippa, V and Mandrioli, J and Pareyson, D and Pisciotta, C and D'Arrigo, S and Ratti, A and Nanetti, L and Mariotti, C and Sarto, E and Pensato, V and Gellera, C and Di Bella, D and Cristofani, RM and Taroni, F and Poletti, A}, title = {Altered molecular and cellular mechanisms in KIF5A-associated neurodegenerative or neurodevelopmental disorders.}, journal = {Cell death & disease}, volume = {15}, number = {9}, pages = {692}, pmid = {39333504}, issn = {2041-4889}, support = {GGP19128//Fondazione Telethon (Telethon Foundation)/ ; 23236//AFM-Téléthon (French Muscular Dystrophy Association)/ ; PRIN n. 2022EFLFL8//Ministero dell'Istruzione, dell'Università e della Ricerca (Ministry of Education, University and Research)/ ; PRIN n. P2022B5J32//Ministero dell'Istruzione, dell'Università e della Ricerca (Ministry of Education, University and Research)/ ; Scientific Exchange Grant n. 9643//European Molecular Biology Organization (EMBO)/ ; 2021-1544//Fondazione Cariplo (Cariplo Foundation)/ ; 2021-1544//Fondazione Cariplo (Cariplo Foundation)/ ; RF-2018-12367768//Ministero della Salute (Ministry of Health, Italy)/ ; RRC 2023//Ministero della Salute (Ministry of Health, Italy)/ ; }, mesh = {Animals ; Humans ; Mice ; Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology ; Charcot-Marie-Tooth Disease/genetics/metabolism/pathology ; *Kinesins/metabolism/genetics ; Mitochondria/metabolism/genetics ; *Mutation/genetics ; Neurodegenerative Diseases/genetics/metabolism/pathology ; *Neurodevelopmental Disorders/genetics/metabolism/pathology ; }, abstract = {Mutations targeting distinct domains of the neuron-specific kinesin KIF5A associate with different neurodegenerative/neurodevelopmental disorders, but the molecular bases of this clinical heterogeneity are unknown. We characterised five key mutants covering the whole spectrum of KIF5A-related phenotypes: spastic paraplegia (SPG, R17Q and R280C), Charcot-Marie-Tooth disease (CMT, R864*), amyotrophic lateral sclerosis (ALS, N999Vfs*40), and neonatal intractable myoclonus (NEIMY, C975Vfs*73) KIF5A mutants. CMT-R864*-KIF5A and ALS-N999Vfs*40-KIF5A showed impaired autoinhibition and peripheral localisation accompanied by altered mitochondrial distribution, suggesting transport competence disruption. ALS-N999Vfs*40-KIF5A formed SQSTM1/p62-positive inclusions sequestering WT-KIF5A, indicating a gain of toxic function. SPG-R17Q-KIF5A and ALS-N999Vfs*40-KIF5A evidenced a shorter half-life compared to WT-KIF5A, and proteasomal blockage determined their accumulation into detergent-insoluble inclusions. Interestingly, SPG-R280C-KIF5A and ALS-N999Vfs*40-KIF5A both competed for degradation with proteasomal substrates. Finally, NEIMY-C975Vfs*73-KIF5A displayed a similar, but more severe aberrant behaviour compared to ALS-N999Vfs*40-KIF5A; these two mutants share an abnormal tail but cause disorders on the opposite end of KIF5A-linked phenotypic spectrum. Thus, our observations support the pathogenicity of novel KIF5A mutants, highlight abnormalities of recurrent variants, and demonstrate that both unique and shared mechanisms underpin KIF5A-related diseases.}, } @article {pmid39332091, year = {2024}, author = {Sharma, O and Kaur Grewal, A and Khan, H and Gurjeet Singh, T}, title = {Exploring the nexus of cGAS STING pathway in neurodegenerative terrain: A therapeutic odyssey.}, journal = {International immunopharmacology}, volume = {142}, number = {Pt B}, pages = {113205}, doi = {10.1016/j.intimp.2024.113205}, pmid = {39332091}, issn = {1878-1705}, mesh = {Humans ; *Membrane Proteins/metabolism/genetics ; Animals ; *Neurodegenerative Diseases/drug therapy/immunology/metabolism ; *Nucleotidyltransferases/metabolism/genetics ; *Signal Transduction ; Immunity, Innate ; }, abstract = {By detecting and responding to cytosolic DNA, the cGAS STING pathway regulates the innate immune responses bymediatinginflammatory reactions and antiviral defense. Thederegulation and modification of this system have been linked to variousneurodegenerative diseases like AD, PD and ALS. Accumulation of tau protein and Aβ aggregates to activate the pathway and releases neuroinflammatory cytokines which accelerates neuronal dysfunction and cognitive impairment as the symptom of AD. Similarly, in PD Alpha-synuclein aggregates activate the cGAS STING pathway and regulate the neuroinflammation and oxidative stress. In ALS, mutation of the genes causes the activation of the pathway which leads to motor neuron degeneration. Alteration of the cGAS STING pathway also leads to mitochondrial dysfunction and impaired autophagy. Preclinical investigations of AD, PD, and ALS animal models showed that STING pathway inhibitors reduced inflammation and improved neurological outcomes and modulators of the cGAS STING pathway may treat these neurodegenerative disorders. In this review we focus on the fact thatneuroinflammation, neuronal dysfunction, and various disease progressions can be treated byaltering the cGAS STING pathway. Understanding the processes and creating specific interventions for this route may offer new treatments for these terrible illnesses.}, } @article {pmid39330700, year = {2024}, author = {Everett, WH and Bucelli, RC}, title = {Tofersen for SOD1 ALS.}, journal = {Neurodegenerative disease management}, volume = {14}, number = {5}, pages = {149-160}, pmid = {39330700}, issn = {1758-2032}, mesh = {Animals ; Humans ; *Amyotrophic Lateral Sclerosis/drug therapy ; *Oligonucleotides/therapeutic use ; *Superoxide Dismutase-1/antagonists & inhibitors ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative condition affecting the motor system. The heterogenous nature of ALS complicates trial design. Genetic forms of ALS present an opportunity to intervene in a less heterogeneous population. ALS associated with gain of function mutations in SOD1 make 'knock-down' strategies an attractive therapeutic approach. Tofersen, an antisense oligonucleotide that reduces expression of SOD1 via RNAase mediated degradation of SOD1 mRNA, has shown robust effects on ALS biomarkers. While a Phase III trial of tofersen failed to meet its primary end point, open label extension data suggests that tofersen slows progression of SOD1 ALS.}, } @article {pmid39329756, year = {2024}, author = {Trainito, A and Muscarà, C and Gugliandolo, A and Chiricosta, L and Salamone, S and Pollastro, F and Mazzon, E and D'Angiolini, S}, title = {Cannabinol (CBN) Influences the Ion Channels and Synaptic-Related Genes in NSC-34 Cell Line: A Transcriptomic Study.}, journal = {Cells}, volume = {13}, number = {18}, pages = {}, pmid = {39329756}, issn = {2073-4409}, support = {Current Research Funds 2024//Ministero della Salute/ ; }, mesh = {*Ion Channels/metabolism/genetics ; Animals ; *Synapses/metabolism/drug effects ; *Transcriptome/drug effects/genetics ; Mice ; Cell Line ; Gene Expression Profiling ; Cannabinoids/pharmacology ; Humans ; Gene Expression Regulation/drug effects ; }, abstract = {Neurological disorders such as Alzheimer's, Parkinson's, amyotrophic lateral sclerosis, and schizophrenia are associated with altered neuronal excitability, resulting from dysfunctions in the molecular architecture and physiological regulation of ion channels and synaptic transmission. Ion channels and synapses are regarded as suitable therapeutic targets in modern pharmacology. Cannabinoids have received great attention as an original therapeutic approach for their effects on human health due to their ability to modulate the neurotransmitter release through interaction with the endocannabinoid system. In our study, we explored the effect of cannabinol (CBN) through next-generation sequencing analysis of NSC-34 cell physiology. Our findings revealed that CBN strongly influences the ontologies related to ion channels and synapse activity at all doses tested. Specifically, the genes coding for calcium and potassium voltage-gated channel subunits, and the glutamatergic and GABAergic receptors (Cacna1b, Cacna1h, Cacng8, Kcnc3, Kcnd1, Kcnd2, Kcnj4, Grik5, Grik1, Slc17a7, Gabra5), were up-regulated. Conversely, the genes involved into serotoninergic and cholinergic pathways (Htr3a, Htr3b, Htr1b, Chrna3, Chrnb2, Chrnb4), were down-regulated. These findings highlight the influence of CBN in the expression of genes involved into ion influx and synaptic transmission.}, } @article {pmid39329381, year = {2025}, author = {Lee, I and Vestrucci, M and Lee, S and Rosenbaum, M and Mitsumoto, H}, title = {Blood glycated hemoglobin level is not associated with disease progression in amyotrophic lateral sclerosis.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {26}, number = {1-2}, pages = {175-179}, pmid = {39329381}, issn = {2167-9223}, support = {K23 NS131586/NS/NINDS NIH HHS/United States ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/blood/diagnosis ; *Glycated Hemoglobin/metabolism ; Male ; Female ; *Disease Progression ; Middle Aged ; Aged ; Cohort Studies ; *Blood Glucose/metabolism ; }, abstract = {OBJECTIVE: A high glycemic index and high glycemic load diet has been associated with slower progression of amyotrophic lateral sclerosis (ALS), suggesting a benefit from high blood glucose levels. We examined the association between average blood glucose level and ALS progression in two independent cohorts.

METHODS: Sporadic ALS patients enrolled in the ALS Multicenter Cohort Study of Oxidative Stress (ALS COSMOS) who completed a 3-month follow-up visit and had available blood samples were included. Hemoglobin A1c (HbA1c) was measured from whole blood collected at the 3-month follow-up. From the Pooled Resource Open-Access ALS Clinical Trials (PRO-ACT) database, we included ALS patients with one or more HbA1c measurements at enrollment and available death information. Associations between HbA1c with revised ALS functional rating scale (ALSFRS-R)/ALSFRS total score change, and tracheostomy-free survival/survival were examined in these cohorts using linear regression, linear mixed-effects models, and Cox proportional hazard models, adjusted for covariates.

RESULTS: In the ALS COSMOS cohort (n = 193), HbA1c level was not significantly associated with the change in the ALSFRS-R total score from baseline to the 3-month follow-up (p = 0.8) nor baseline to the 6-month follow-up (p = 0.4). No significant association was found between HbA1c level and tracheostomy-free survival (p = 0.8). In the PRO-ACT cohort (n = 928), no significant association was found between HbA1c level and the rate of ALSFRS decline in the first 200 days (p = 0.81 for interaction) nor between HbA1c level and survival (p = 0.45).

INTERPRETATION: We did not find convincing evidence that mean blood glucose level is associated with disease progression among ALS patients.}, } @article {pmid39328853, year = {2024}, author = {Ali, M and Ramadan, A and Surani, S}, title = {Obstructive sleep apnea-hypopnea syndrome immunological relationship.}, journal = {World journal of clinical cases}, volume = {12}, number = {27}, pages = {6011-6014}, pmid = {39328853}, issn = {2307-8960}, abstract = {Obstructive sleep apnea-hypopnea syndrome (OSAHS) is a complex disorder characterized by symptoms resulting from intermittent hypoxia and hypopnea, with research indicating a crucial role of immune system dysregulation and genetic variations in its pathogenesis. A recent Zhao et al study utilizes Mendelian randomization analysis to explore the causal relationship between immune cell characteristics and OSAHS. The study identifies specific lymphocyte subsets associated with OSAHS, providing valuable insights into the disease's pathophysiology and potential targets for therapeutic intervention. The findings underscore the significance of genetic and immunological factors in sleep disorders, offering a fresh perspective on OSAHS's complexities. Compared to existing literature, Zhao et al's study stands out for its focus on genetic markers and specific immune responses associated with OSAHS, expanding upon previous research primarily centered on systemic inflammation. In conclusion, the study represents a significant advancement in the field, shedding light on the causal role of immune cells in OSAHS and paving the way for future research and targeted treatments.}, } @article {pmid39328135, year = {2024}, author = {Sharma, S and Mehan, S and Khan, Z and Tiwari, A and Kumar, A and Gupta, GD and Narula, AS and Kalfin, R}, title = {Exploring the Neuroprotective Potential of Icariin through Modulation of Neural Pathways in the Treatment of Neurological Diseases.}, journal = {Current molecular medicine}, volume = {}, number = {}, pages = {}, doi = {10.2174/0115665240317650240924041923}, pmid = {39328135}, issn = {1875-5666}, abstract = {Neuropathological diseases involve the death of neurons and the aggregation of proteins with altered properties in the brain. Proteins are used at the molecular level to categorize neurodegenerative disorders, emphasizing the importance of protein-processing mechanisms in their development. Natural herbal phytoconstituents, such as icariin, have addressed these neurological complications. Icariin, the principal compound in Epimedium, has been studied for its antineuroinflammatory, anti-oxidative, and antiapoptotic properties. Recent scientific investigations have shown that icariin exhibits promising therapeutic and preventive properties for mental and neurodegenerative disorders. In preclinical, icariin has been shown to inhibit amyloid development and reduce the expression of APP and BACE-1. Previous preclinical studies have demonstrated that icariin can regulate proinflammatory responses in neurological conditions like Parkinson's disease, depression, cerebral ischemia, ALS, and multiple sclerosis. Studies have shown that icariin possesses neuroprotective properties by modulating signaling pathways and crossing the blood-brain barrier, suggesting its potential to address various neurocomplications. This review aims to establish a foundation for future clinical investigations by examining the existing literature on icariin and exploring its potential therapeutic implications in treating neurodegenerative disorders and neuropsychiatric conditions. Future research may address numerous concerns and yield captivating findings with far-reaching implications for various aspects of icariin.}, } @article {pmid39328012, year = {2024}, author = {Cui, Y and Chen, J and Li, H and Zheng, D and Shi, X}, title = {The causal association between epilepsy and amyotrophic lateral sclerosis: A two-sample Mendelian randomization study.}, journal = {Brain and behavior}, volume = {14}, number = {10}, pages = {e70018}, pmid = {39328012}, issn = {2162-3279}, support = {2023A03J0438//Science and Technology Program of Guangzhou/ ; 2020A1515010063//Natural Science Foundation of Guangdong Province/ ; 2023A1515011047//Natural Science Foundation of Guangdong Province/ ; //Guangzhou Research-oriented Hospital/ ; //Guangzhou High-level Clinical Key Specialty/ ; 2022A1515220119//Basic and Applied Basic Research Foundation of Guangdong Province/ ; 2021-2023//Guangzhou Municipal Key Discipline in Medicine/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/genetics/epidemiology ; Humans ; *Mendelian Randomization Analysis ; *Epilepsy/genetics/epidemiology/etiology ; *Genome-Wide Association Study ; Causality ; }, abstract = {OBJECTIVES: Epilepsy and amyotrophic lateral sclerosis (ALS) are common neurological disorders. The association between the two disorders has been raised in observational studies. However, it is uncertain to what extent they have mutual causal effects. In this study, we aimed to investigate their causal association using a two-sample Mendelian randomization (MR) method.

METHODS: We performed a two-sample bidirectional MR analysis to evaluate the causal association of epilepsy with the risk of ALS. Publicly published genome-wide association study statistics for epilepsy and ALS were used in the study. The primary analysis included genetic variants with a p value of less than 1 × 10[-5] as instrumental variables. We applied several alternative methods, including inverse variance weighting, weighted median, simple mode, weighted mode, MR-Egger regression and MR pleiotropy residual sum and outlier, and statistical graphs to assess the associations of epilepsy and its subtype with the risk of ALS. Reverse MR analyses were also performed to examine the association of ALS with the risk of epilepsy.

RESULTS: The primary MR analysis found no causal effect of epilepsy on risk of ALS (odds ration [OR]: 1.133, 95% confidence interval [CI]: 0.964-1.332, p = .130). Among subtypes of epilepsy, it also failed to observe any causal association between general epilepsy and ALS (OR: 1.036, 95% CI: 0.969-1.108, P = .300). However, focal epilepsy contributed to an increase in the risk of ALS (OR: 1.177, 95% CI: 1.027-1.348, p = .019). Moreover, the investigation of reverse causalities did not reveal significant results.

CONCLUSIONS: The current study supports a causal influence of focal epilepsy on ALS risk. Future studies are needed to explore its potential role in ALS.}, } @article {pmid39327888, year = {2024}, author = {Fitri, HU and Saputra, R and Suhardita, K and Suarta, IM and Oktasari, M and Aminah, S and Laras, PB}, title = {Digging deeper: A critique of the mediation study of spirituality in ALS patients.}, journal = {Palliative & supportive care}, volume = {22}, number = {5}, pages = {1550-1551}, doi = {10.1017/S1478951524001275}, pmid = {39327888}, issn = {1478-9523}, } @article {pmid39327159, year = {2024}, author = {Vassallu, F and Igaz, LM}, title = {TDP-43 nuclear condensation and neurodegenerative proteinopathies.}, journal = {Trends in neurosciences}, volume = {47}, number = {11}, pages = {849-850}, doi = {10.1016/j.tins.2024.09.003}, pmid = {39327159}, issn = {1878-108X}, mesh = {Animals ; Humans ; Cell Nucleus/metabolism ; *DNA-Binding Proteins/metabolism/genetics ; Neurodegenerative Diseases/metabolism ; *TDP-43 Proteinopathies/metabolism/genetics/pathology ; }, abstract = {RNA-binding proteins (RBPs) can undergo phase separation and form condensates, processes that, in turn, can be critical for their functionality. In a recent study, Huang, Ellis, and colleagues show that cellular stress can trigger transient alterations in nuclear TAR DNA-binding protein 43 (TDP-43), leading to changes crucial for proper neuronal function. These findings have implications for understanding neurological TDP-43 proteinopathies.}, } @article {pmid39326369, year = {2024}, author = {Suzuki, Y and Adachi, T and Yoshida, K and Sakuwa, M and Hanajima, R}, title = {Psychiatric symptoms and TDP-43 pathology in amyotrophic lateral sclerosis.}, journal = {Journal of the neurological sciences}, volume = {466}, number = {}, pages = {123249}, doi = {10.1016/j.jns.2024.123249}, pmid = {39326369}, issn = {1878-5883}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/pathology/metabolism/psychology ; Male ; Female ; Aged ; *DNA-Binding Proteins/metabolism ; Middle Aged ; Mental Disorders/etiology/pathology/metabolism ; Brain/pathology/metabolism ; Aged, 80 and over ; Neurons/pathology/metabolism ; }, abstract = {BACKGROUND: ALS is not a pure motor neuron disease but co-occurs with cognitive impairment and psychiatric symptoms. The neuropathological origin of the psychiatric symptoms is unclear. This study examined the association between the psychiatric symptoms and neuropathology of ALS.

METHODS: We investigated the clinicopathological characteristics of 15 autopsy cases of ALS, including neuronal loss, gliosis, and the burden of TDP-43 pathology. We divided TDP-43-positive structures by morphology into four categories (neuronal cytoplasmic inclusion, dystrophic neurite, dot, and glial cytoplasmic inclusion) and gave each a semiquantitative score in nine brain regions. Braak neurofibrillary tangle stage, Thal amyloid phase, Lewy-related pathology, and argyrophilic grains were also assessed.

RESULTS: Of the 15 ALS patients, seven had presented with psychiatric symptoms and eight had not. Significantly higher TDP-43 pathology scores were found in the group with psychiatric symptoms in the temporal tip, transentorhinal cortex, entorhinal cortex, subiculum, and the hippocampal CA1 region and dentate gyrus. Cognitive impairment was not significantly associated with the degree of TDP-43 pathology. There were no significant differences in the degree of neuronal loss/gliosis or in other concurrent pathologies between patients with and without psychiatric symptoms. Morphological evaluation showed that neuronal cytoplasmic inclusions, dystrophic neurites, and dots tended to be more common in the group with psychiatric symptoms.

CONCLUSION: Psychiatric symptoms in ALS may be related to TDP-43 pathology in the perforant pathway. (224 words).}, } @article {pmid39324867, year = {2024}, author = {Li, J and Gao, C and Wang, Q and Liu, J and Xie, Z and Zhao, Y and Yu, M and Zheng, Y and Lv, H and Zhang, W and Yuan, Y and Meng, L and Deng, J and Wang, Z}, title = {Elevated serum circulating cell-free mitochondrial DNA in amyotrophic lateral sclerosis.}, journal = {European journal of neurology}, volume = {31}, number = {12}, pages = {e16493}, pmid = {39324867}, issn = {1468-1331}, support = {82071409//National Natural Science Foundation of China/ ; 82101469//National Natural Science Foundation of China/ ; 82171846//National Natural Science Foundation of China/ ; U20A20356//National Natural Science Foundation of China/ ; 2022-4-40716//Capitals Funds for Health Improvement and Research/ ; 20220484017//Beijing Nova Program/ ; 20230484403//Beijing Nova Program/ ; 2023CX05//Scientific and Technological Achievements Transformation Incubation Guidance Fund Project of Peking University First Hospital/ ; 2023HQ03//National High Level Hospital Clinical Research Funding (High Quality Clinical Research Project of Peking University First Hospital/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/blood/genetics ; Male ; Female ; *DNA, Mitochondrial/blood/genetics ; Middle Aged ; Aged ; *Interleukin-6/blood ; *Cell-Free Nucleic Acids/blood ; *Superoxide Dismutase-1/blood/genetics ; Mutation ; Adult ; Biomarkers/blood ; }, abstract = {BACKGROUND AND PURPOSE: The substantial role of inflammation in amyotrophic lateral sclerosis (ALS) is gaining support from recent research. Studies indicate that circulating cell-free mitochondrial DNA (ccf-mtDNA) can activate the immune system and is associated with neurodegenerative diseases. This research was designed to quantify ccf-mtDNA levels in the serum of ALS patients.

METHODS: The medical records of ALS patients were reviewed. Serum ccf-mtDNA levels of patients with ALS (n = 62) and age-matched healthy controls (n = 46) were measured and compared. Additionally, serum interleukin-6 (IL-6) levels were measured using an enzyme-linked immunosorbent assay in 26 ALS patients. Correlations between variables were analyzed.

RESULTS: Serum ccf-mtDNA was notably higher in the patients with ALS. When stratified by genotype, the superoxide dismutase 1 (SOD1) mutation group showed the greatest increase in ccf-mtDNA levels relative to other ALS patients. Among all 108 individuals, a cut-off set at 1.1 × 10[5] mtDNA copies on a receiver-operating characteristic curve identified patients with ALS with 80.7% sensitivity and 50.0% specificity; the area under the curve was 0.69 (p < 0.001). Furthermore, serum ccf-mtDNA levels correlated negatively with the progression rate of ALS (ΔFS; rs = -0.26, p = 0.044), but not the ALSFRS-R score (rs = 0.06, p = 0.625). Importantly, the correlation between ccf-mtDNA and ΔFS was more pronounced in the SOD1 mutation group (rs = -0.62, p = 0.018). Lastly, a significant positive association was observed between serum ccf-mtDNA levels and IL-6 levels in ALS (r s= 0.41, p = 0.038).

CONCLUSION: Our study found increased serum ccf-mtDNA in ALS patients, suggesting a link to inflammatory processes and disease mechanism. Moreover, ccf-mtDNA could be an indicator for ALS progression, especially in those with the SOD1 mutation.}, } @article {pmid39323877, year = {2024}, author = {Engelberg-Cook, E and Shah, JS and Teixeira da Silva Hucke, A and Vera-Garcia, DV and Dagher, JE and Donahue, MH and Belzil, VV and Oskarsson, B}, title = {Prognostic Factors and Epidemiology of Amyotrophic Lateral Sclerosis in Southeastern United States.}, journal = {Mayo Clinic proceedings. Innovations, quality & outcomes}, volume = {8}, number = {5}, pages = {482-492}, pmid = {39323877}, issn = {2542-4548}, abstract = {OBJECTIVE: To assess the performance of known survival predictors and evaluate their stratification capability in patients with amyotrophic lateral sclerosis (ALS).

PATIENTS AND METHODS: We analyzed demographic and clinical variables collected at the Mayo Clinic, Florida ALS center during the first clinical visit of 1442 (100%) patients with ALS.

RESULTS: Our cohort had a median (interquartile range [IQR]) age at diagnosis of 64.8 (57-72) years; 1350 (92%) were non-Hispanic White; and 771 (53.5%) were male. The median (IQR) diagnostic delay was 10.1 (6-18) months, body mass index was 25.4 (23-49), and forced vital capacity was 72% (52%-87%). Approximately 12% of patients tested carried a pathologic C9orf72 hexanucleotide repeat expansion. Median (IQR) ALS functional rating scale-revised score was 35 (29-40) and ALS cognitive behavioral screen score was 15 (12-17). The median (IQR) survival after diagnosis was 17.2 (9-31) months, and survival from symptom onset was 30 (20-48) months. We found that older age decreased forced vital capacity, and fast-progressing ALS functional rating scale-revised scores significantly (P<.0001) influence survival curves and associated hazard risk.

CONCLUSION: Although results obtained from our cohort are consistent with other reports (eg, men with spinal onset experience a longer survival than women with bulbar onset), they remind us of the complexity of the disease's natural history and the limited prognostic power of the most common clinical predictors.}, } @article {pmid39323817, year = {2024}, author = {Zeng, A and Huang, Y and Xin, J and Li, J and Qiu, W and Zhang, M}, title = {Progress and recommendations of developing occupational exposure limits for noise-A systematic review.}, journal = {Heliyon}, volume = {10}, number = {18}, pages = {e37878}, pmid = {39323817}, issn = {2405-8440}, abstract = {OBJECTIVE: Noise exposure limit is one of the critical measures to prevent noise-induced hearing loss (NIHL). This review aimed to review the progress and recommendations for developing occupational exposure limits (OELs) for workplace noise.

METHODS: A systematic review was used. Thirty-eight national or international organizations' noise exposure standards (including OEL) and laws, regulations, and guidelines for noise exposure control were analyzed. Articles on recommendations for revising noise OEL standards between 2000 and 2023 were selected.

RESULTS: The definition of different noise types (especially for non-steady and impulsive noise) varied worldwide, and the used 8-h OEL varied from 80 to 90 dB(A). Maximum sound pressure level (Lmax) and noise dose for industrial noise and peak sound pressure level (Lpeak) for impulsive noise have been incorporated into the OELs. Countries developed noise risk management measures based on OELs, action levels (ALs), and exposure risk ratio or classification. The risk of co-exposure to noise and ototoxic organic substances and the effects of noise on susceptible populations were concerns in EU country standards. Scholars suggested revising the existing noise exposure standards based on noise's temporal structure (expressed by kurtosis), effective noise level, impulsive noise OEL, action level, and key factors of risk assessment.

CONCLUSIONS: Indicators such as Lmax, noise dose, Lpeak, and action level can be incorporated into noise OELs. Developing noise OEL standards should consider the co-exposure of noise and ototoxic substances, HPD's noise attenuation, susceptible groups, and noise's temporal structure.}, } @article {pmid39323783, year = {2024}, author = {You, J and Maksimovic, K and Metri, MN and Schoeppe, A and Chen, K and Lee, J and Santos, JR and Youssef, MMM and Salter, MW and Park, J}, title = {Knockout of Dectin-1 does not modify disease onset or progression in a MATR3 S85C knock-in mouse model of ALS.}, journal = {Heliyon}, volume = {10}, number = {18}, pages = {e37926}, pmid = {39323783}, issn = {2405-8440}, abstract = {Microglia have been increasingly implicated in neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). Dectin-1, encoded by the Clec7a gene, is highly upregulated in a specific microglial response state called disease-associated microglia (DAM) in various neurodegenerative conditions. However, the role of Dectin-1 in ALS is undetermined. Here, we show that Clec7a mRNA upregulation occurs in central nervous system (CNS) regions that exhibit neurodegeneration in a MATR3 S85C knock-in mouse model (Matr3 [S85C/S85C]) of ALS. Furthermore, a significant increase in the number of Dectin-1[+] microglia coincides with the onset of motor deficits, and this number increases with disease progression. We demonstrate that the knockout of Dectin-1 does not affect survival, motor function, neurodegeneration, or microglial responses in Matr3 [S85C/S85C] mice. These findings suggest that Dectin-1 does not play a role in modifying ALS onset or progression.}, } @article {pmid39322357, year = {2024}, author = {Mehta, RI and Ranjan, M and Haut, MW and Carpenter, JS and Rezai, AR}, title = {Focused Ultrasound for Neurodegenerative Diseases.}, journal = {Magnetic resonance imaging clinics of North America}, volume = {32}, number = {4}, pages = {681-698}, doi = {10.1016/j.mric.2024.03.001}, pmid = {39322357}, issn = {1557-9786}, mesh = {Humans ; *Neurodegenerative Diseases/diagnostic imaging ; Ultrasonic Therapy/methods ; Brain/diagnostic imaging ; Animals ; }, abstract = {Neurodegenerative diseases are a leading cause of death and disability and pose a looming global public health crisis. Despite progress in understanding biological and molecular factors associated with these disorders and their progression, effective disease modifying treatments are presently limited. Focused ultrasound (FUS) is an emerging therapeutic strategy for Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. In these contexts, applications of FUS include neuroablation, neuromodulation, and/or blood-brain barrier opening with and without facilitated intracerebral drug delivery. Here, the authors review preclinical evidence and current and emerging applications of FUS for neurodegenerative diseases and summarize future directions in the field.}, } @article {pmid39321879, year = {2024}, author = {Lei, T and Zhang, X and Fu, G and Luo, S and Zhao, Z and Deng, S and Li, C and Cui, Z and Cao, J and Chen, P and Yang, H}, title = {Advances in human cellular mechanistic understanding and drug discovery of brain organoids for neurodegenerative diseases.}, journal = {Ageing research reviews}, volume = {102}, number = {}, pages = {102517}, doi = {10.1016/j.arr.2024.102517}, pmid = {39321879}, issn = {1872-9649}, mesh = {Humans ; *Organoids/drug effects/pathology ; *Neurodegenerative Diseases/pathology/drug therapy ; *Drug Discovery/methods ; *Brain/pathology/drug effects ; Animals ; }, abstract = {The prevalence of neurodegenerative diseases (NDs) is increasing rapidly as the aging population accelerates, and there are still no treatments to halt or reverse the progression of these diseases. While traditional 2D cultures and animal models fail to translate into effective therapies benefit patients, 3D cultured human brain organoids (hBOs) facilitate the use of non-invasive methods to capture patient data. The purpose of this study was to review the research and application of hBO in disease models and drug screening in NDs. The pluripotent stem cells are induced in multiple stages to form cerebral organoids, brain region-specific organoids and their derived brain cells, which exhibit complex brain-like structures and perform electrophysiological activities. The brain region-specific organoids and their derived neurons or glial cells contribute to the understanding of the pathogenesis of NDs and the efficient development of drugs, including Alzheimer's disease, Parkinson's disease, Huntington's disease and Amyotrophic lateral sclerosis. Glial-rich brain organoids facilitate the study of glial function and neuroinflammation, including astrocytes, microglia, and oligodendrocytes. Further research on the maturation enhancement, vascularization and multi-organoid assembly of hBO will help to enhance the research and application of NDs cellular models.}, } @article {pmid39319809, year = {2024}, author = {Karra, R and Rice, AD and Hardcastle, A and V Lara, J and Hollen, A and Glenn, M and Munn, R and Hannan, P and Arcaris, B and Derksen, D and Spaite, DW and Gaither, JB}, title = {Telemedical Direction to Optimize Resource Utilization in a Rural Emergency Medical Services System.}, journal = {The western journal of emergency medicine}, volume = {25}, number = {5}, pages = {777-783}, pmid = {39319809}, issn = {1936-9018}, mesh = {Humans ; Retrospective Studies ; *Telemedicine ; *Emergency Medical Services ; *Rural Health Services ; Female ; *Emergency Medical Technicians ; Male ; Chest Pain/therapy ; Middle Aged ; Pilot Projects ; Adult ; }, abstract = {BACKGROUND: Telemedicine remains an underused tool in rural emergency medical servces (EMS) systems. Rural emergency medical technicians (EMT) and paramedics cite concerns that telemedicine could increase Advanced Life Support (ALS) transports, extend on-scene times, and face challenges related to connectivity as barriers to implementation. Our aim in this project was to implement a telemedicine system in a rural EMS setting and assess the impact of telemedicine on EMS management of patients with chest pain while evaluating some of the perceived barriers.

METHODS: This study was a mixed-methods, retrospective review of quality assurance data collected prior to and after implementation of a telemedicine program targeting patients with chest pain. We compared quantitative data from the 12-month pre-implementation phase to data from 15 months post-implementation. Patients were included if they had a chief complaint of chest pain or a 12-lead electrocardiogram had been obtained. The primary outcome was the rate of ALS transport before and after program implementation. Secondary outcomes included EMS call response times and EMS agency performance on quality improvement benchmarks. Qualitative data were also collected after each telemedicine encounter to evaluate paramedic/EMT and EMS physician perception of call quality.

RESULTS: The telemedicine pilot project was implemented in September 2020. Overall, there were 58 successful encounters. For this analysis, we included 38 patients in both the pre-implementation period (September 9, 2019-September 10, 2020) and the post-implementation period (September 11, 2020-December 5, 2021). Among this population, the ALS transport rate was 42% before and 45% after implementation (odds ratio 1.11; 95% confidence interval 0.45-2.76). The EMS median out-of-service times were 47 minutes before, and 33 minutes after (P = 0.07). Overall, 64% of paramedics/EMTs and 89% of EMS physicians rated the telemedicine call quality as "good."

CONCLUSION: In this rural EMS system, a telehealth platform was successfully used to connect paramedics/EMTs to board-certified EMS physicians over a 15-month period. Telemedicine use did not alter rates of ALS transports and did not increase on-scene time. The majority of paramedics/EMTs and EMS physicians rated the quality of the telemedicine connection as "good."}, } @article {pmid39318842, year = {2024}, author = {Emary, PC and Turner, AJ}, title = {Cervical spondylotic myelopathy in a 68-year-old man diagnosed with amyotrophic lateral sclerosis.}, journal = {The Journal of the Canadian Chiropractic Association}, volume = {68}, number = {2}, pages = {172-176}, pmid = {39318842}, issn = {0008-3194}, abstract = {Owing to similar clinical presentations, cervical spondylotic myelopathy can mimic other neurological disorders. In this imaging case review (ICR), we describe a case of cervical spondylotic myelopathy in a patient diagnosed with amyotrophic lateral sclerosis. The key clinical features, imaging findings and differential diagnoses of cervical spondylotic myelopathy compared with amyotrophic lateral sclerosis are also presented.}, } @article {pmid39318236, year = {2025}, author = {Majewski, S and Klein, P and Boillée, S and Clarke, BE and Patani, R}, title = {Towards an integrated approach for understanding glia in Amyotrophic Lateral Sclerosis.}, journal = {Glia}, volume = {73}, number = {3}, pages = {591-607}, pmid = {39318236}, issn = {1098-1136}, support = {MR/S006591/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {*Amyotrophic Lateral Sclerosis/pathology/metabolism ; Humans ; *Neuroglia/metabolism/pathology ; Animals ; }, abstract = {Substantial advances in technology are permitting a high resolution understanding of the salience of glia, and have helped us to transcend decades of predominantly neuron-centric research. In particular, recent advances in 'omic' technologies have enabled unique insights into glial biology, shedding light on the cellular and molecular aspects of neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). Here, we review studies using omic techniques to attempt to understand the role of glia in ALS across different model systems and post mortem tissue. We also address caveats that should be considered when interpreting such studies, and how some of these may be mitigated through either using a multi-omic approach and/or careful low throughput, high fidelity orthogonal validation with particular emphasis on functional validation. Finally, we consider emerging technologies and their potential relevance in deepening our understanding of glia in ALS.}, } @article {pmid39317854, year = {2025}, author = {Khoshdooz, S and Abbasi, H and Abbasi, MM}, title = {Iron-Status Indicators and HFE Gene Polymorphisms in Individuals with Amyotrophic Lateral Sclerosis: An Umbrella Review of Meta-analyses and Systematic Reviews.}, journal = {Biological trace element research}, volume = {203}, number = {6}, pages = {2974-2985}, pmid = {39317854}, issn = {1559-0720}, mesh = {*Amyotrophic Lateral Sclerosis/genetics/blood ; Humans ; *Hemochromatosis Protein/genetics ; *Iron/blood/metabolism ; Systematic Reviews as Topic ; *Polymorphism, Genetic ; Meta-Analysis as Topic ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the progressive loss of motor neurons. Recent meta-analyses and systematic reviews suggest that HFE gene polymorphisms and iron-associated biomarkers may play a key role in the risk and occurrence of ALS. This umbrella study aimed to explore the roles of HFE gene polymorphisms and iron-associated biomarkers in individuals with ALS. A thorough search of three online scientific databases, namely Scopus, Web of Science, and PubMed, was conducted from their inception until September 13, 2024. The screening and selection processes were executed based on the PICO framework and eligibility criteria, followed by two independent reviewers. The Assessment of Multiple Systematic Reviews (AMSTAR)-2 and GRADE tools were utilized to assess the methodological quality and the certainty of evidence. Through an advanced search, 101 records were retrieved, of which eight meta-analyses and systematic reviews were selected for this umbrella review. A significant increase in iron concentrations was found in individuals with ALS compared to healthy controls (SMD, 0.26; 95% CI - 0.05, 0.57). Conversely, selected meta-analyses reported that serum transferrin concentrations in ALS patients were lower compared to healthy controls (SMD, - 0.15; 95% CI - 0.36, 0.05). Furthermore, mutations in H63D polymorphisms resulted in a 13% significant increase in the risk of ALS (OR, 1.13; 95% CI 1.05, 1.22). Our umbrella study of meta-analyses and systematic reviews reveals that individuals with ALS have lower serum concentrations of transferrin compared to healthy controls. Additionally, the H63D polymorphism in the HFE gene is associated with a slight increase in the risk of ALS. Future research should investigate broader aspects of iron-related biomarkers and HFE genes to elucidate their roles in ALS pathogenesis. Registration: Our umbrella study was registered in the International Prospective Register of Systematic Reviews (PROSPERO) with the identification number CRD42024559032 (https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024559032).}, } @article {pmid39317352, year = {2025}, author = {Kleinerova, J and Garcia-Gallardo, A and Tacheva, A and Bede, P}, title = {Subcortical grey matter involvement in ALS and PLS - vulnerable hubs of cortico-cortical and cortico-basal circuits: extrapyramidal, cognitive, bulbar and respiratory correlates.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {26}, number = {1-2}, pages = {1-4}, doi = {10.1080/21678421.2024.2405130}, pmid = {39317352}, issn = {2167-9223}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology/diagnostic imaging/pathology/complications ; *Gray Matter/pathology/diagnostic imaging/physiopathology ; *Cerebral Cortex/pathology/physiopathology/diagnostic imaging ; Neural Pathways/pathology/physiopathology/diagnostic imaging ; *Nerve Net/pathology/physiopathology ; }, abstract = {Evidence from neuroimaging studies suggests that the cardinal clinical manifestations of ALS stem from the dysfunction of specific neural networks. The majority of cortico-cortical and cortico-basal networks are physiologically relayed by deep cerebral and cerebellar grey matter nuclei which have been increasingly implicated in the pathophysiology of ALS. A series of recent human imaging papers revealed volume reductions, shape deformations, metabolic alterations and more recently, susceptibility changes in hippocampal subfields, thalamic, striatal, amygdalar and cerebellar nuclei. Thalamic changes have been identified in presymptomatic mutation carriers long before symptom onset and longitudinal studies have consistently confirmed progressive subcortical degeneration during the symptomatic phase of the disease. The dysfunction of circuits relayed by specific subcortical nuclei has been associated with apathy, amnestic deficits, limbic symptoms, extrapyramidal manifestations, sensory disturbances, pseudobulbar affect and cerebellar deficits. In light of emerging imaging data, the clinical heterogeneity of ALS is probably best approached from a network integrity perspective. Accordingly, the comprehensive assessment of subcortical grey matter nuclei seems imperative to untangle complex clinical phenomena in ALS.}, } @article {pmid39316747, year = {2024}, author = {de Calbiac, H and Renault, S and Haouy, G and Jung, V and Roger, K and Zhou, Q and Campanari, ML and Chentout, L and Demy, DL and Marian, A and Goudin, N and Edbauer, D and Guerrera, C and Ciura, S and Kabashi, E}, title = {Poly-GP accumulation due to C9orf72 loss of function induces motor neuron apoptosis through autophagy and mitophagy defects.}, journal = {Autophagy}, volume = {20}, number = {10}, pages = {2164-2185}, pmid = {39316747}, issn = {1554-8635}, mesh = {*Motor Neurons/metabolism/pathology ; Animals ; *C9orf72 Protein/genetics/metabolism ; *Zebrafish ; *Mitophagy/genetics ; *Apoptosis/genetics ; Humans ; *Autophagy/genetics/physiology ; *Amyotrophic Lateral Sclerosis/metabolism/pathology/genetics ; *Dipeptides/pharmacology/metabolism ; Loss of Function Mutation/genetics ; Mitochondria/metabolism ; Disease Models, Animal ; }, abstract = {The GGGGCC hexanucleotide repeat expansion (HRE) of the C9orf72 gene is the most frequent cause of amyotrophic lateral sclerosis (ALS), a devastative neurodegenerative disease characterized by motor neuron degeneration. C9orf72 HRE is associated with lowered levels of C9orf72 expression and its translation results in the production of dipeptide-repeats (DPRs). To recapitulate C9orf72-related ALS disease in vivo, we developed a zebrafish model where we expressed glycine-proline (GP) DPR in a c9orf72 knockdown context. We report that C9orf72 gain- and loss-of-function properties act synergistically to induce motor neuron degeneration and paralysis with poly(GP) accumulating preferentially within motor neurons along with Sqstm1/p62 aggregation indicating macroautophagy/autophagy deficits. Poly(GP) levels were shown to accumulate upon c9orf72 downregulation and were comparable to levels assessed in autopsy samples of patients carrying C9orf72 HRE. Chemical boosting of autophagy using rapamycin or apilimod, is able to rescue motor deficits. Proteomics analysis of zebrafish-purified motor neurons unravels mitochondria dysfunction confirmed through a comparative analysis of previously published C9orf72 iPSC-derived motor neurons. Consistently, 3D-reconstructions of motor neuron demonstrate that poly(GP) aggregates colocalize to mitochondria, thus inducing their elongation and swelling and the failure of their processing by mitophagy, with mitophagy activation through urolithin A preventing locomotor deficits. Finally, we report apoptotic-related increased amounts of cleaved Casp3 (caspase 3, apoptosis-related cysteine peptidase) and rescue of motor neuron degeneration by constitutive inhibition of Casp9 or treatment with decylubiquinone. Here we provide evidence of key pathogenic steps in C9ALS-FTD that can be targeted through pharmacological avenues, thus raising new therapeutic perspectives for ALS patients.}, } @article {pmid39316061, year = {2025}, author = {Yang, W and Liu, X and Fan, D}, title = {Low CD3 level is a risk factor for amyotrophic lateral sclerosis: a Mendelian randomization study.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {26}, number = {1-2}, pages = {64-72}, doi = {10.1080/21678421.2024.2407408}, pmid = {39316061}, issn = {2167-9223}, mesh = {*Amyotrophic Lateral Sclerosis/genetics/immunology ; Humans ; *Mendelian Randomization Analysis/methods ; *CD3 Complex/genetics/metabolism ; Risk Factors ; Genetic Predisposition to Disease/genetics ; Male ; Female ; Polymorphism, Single Nucleotide/genetics ; CD8-Positive T-Lymphocytes/metabolism/immunology ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive and fatal disease characterized by neuronal degeneration of the spinal cord and brain and believed to be related to the immune system. In this study, our aim is to use Mendelian randomization (MR) to search for immune markers related to ALS. A total of 731 immune cell traits were included in this study. MR analysis was used to identify the causality between 731 immune cell traits (with 3,757 Europeans) and ALS (with 138,086 Europeans). Colocalization analysis was used to verify the found causality, protein-protein interaction prediction was used to look for the interacting proteins that are known to be involved in ALS. We found low expression levels of CD3 on central memory CD8+ T cell is risk factor for ALS (OR = 0.90, 95% CI: 0.86-0.95, P = 0.0000303). CD3 can interact with three ALS-related proteins: VCP, HLA-DRA and HLA-DRB5, which are associated with adaptive immune response. Our study reported for the first time that low-level CD3 is a risk factor for ALS and the possible mechanism, which could provide a potential strategy for ALS diagnosis and therapy.}, } @article {pmid39316038, year = {2025}, author = {Olsen, CG and Malmberg, VN and Fahlström, M and Alstadhaug, KB and Bjørnå, IK and Braathen, GJ and Bråthen, G and Demic, N and Hallerstig, E and Hogenesch, I and Horn, MA and Kampman, MT and Kleveland, G and Ljøstad, U and Maniaol, A and Morsund, ÅH and Nakken, O and Schlüter, K and Schuler, S and Seim, E and Flemmen, HØ and Tysnes, OB and Holmøy, T and Høyer, H}, title = {Amyotrophic lateral sclerosis caused by the C9orf72 expansion in Norway - prevalence, ancestry, clinical characteristics and sociodemographic status.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {26}, number = {1-2}, pages = {132-140}, doi = {10.1080/21678421.2024.2405118}, pmid = {39316038}, issn = {2167-9223}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/epidemiology ; Male ; Female ; Norway/epidemiology ; *C9orf72 Protein/genetics ; Middle Aged ; Aged ; Prevalence ; Adult ; *DNA Repeat Expansion/genetics ; *Proteins/genetics ; Aged, 80 and over ; }, abstract = {OBJECTIVE: The most common genetic cause of amyotrophic lateral sclerosis (ALS) is the C9orf72 expansion. A high incidence of this expansion has been detected in Sweden and Finland. This Norwegian population-based study aimed to identify the prevalence, geographic distribution, ancestry, and relatedness of ALS patients with a C9orf72 expansion (C9pos). Further, we compared C9pos and C9neg patients' clinical presentation, family history of ALS and other neurodegenerative disorders, and sociodemographic status.

METHODS: We recruited ALS patients from all 17 Departments of neurology in Norway. Blood samples and questionnaires regarding clinical characteristics, sociodemographic status and family history of ALS, and other neurodegenerative disorders were collected. The C9orf72 expansion was examined for all patients.

RESULTS: The study enrolled 500 ALS patients, 8.8% of whom were C9pos, with half being sporadic ALS cases. The proportion of C9pos cases differed between regions, ranging from 17.9% in the Northern region to 1.9% in the Western region. The majority of C9pos patients had non-Finnish European descent and were not closely related. C9pos patients exhibited a significantly shorter mean survival time, had a higher frequency of relatives with ALS or dementia, and were more often unmarried/single and childless than C9neg patients.

CONCLUSION: C9pos patients constitute a large portion of the Norwegian ALS population. Ancestry and relatedness do not adequately explain regional differences. Relying on clinical information to identify C9pos patients has proven to be challenging. Half of C9pos patients were reported as having sporadic ALS, underlining the importance of carefully assessing family history and the need for genetic testing.}, } @article {pmid39315390, year = {2024}, author = {Douglas, AGL and Thompson, AG and Turner, MR and Talbot, K}, title = {Personalised penetrance estimation for C9orf72-related amyotrophic lateral sclerosis and frontotemporal dementia.}, journal = {BMJ neurology open}, volume = {6}, number = {2}, pages = {e000792}, pmid = {39315390}, issn = {2632-6140}, abstract = {BACKGROUND: C9orf72 hexanucleotide repeat expansions are the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) in European populations. Variable disease penetrance between families presents a challenge for genetic counselling of at-risk relatives and reduces the predictive utility of testing asymptomatic relatives. We have developed a novel model for estimating penetrance in individual families affected by C9orf72 using available family history information, allowing the calculation of personalised risk estimates.

METHODS: Published aggregated age-of-onset data for C9orf72-related ALS/FTD were used to generate age-related cumulative relative risks for at-risk relatives within pedigrees. Age-related relative risks are combined with a priori chance of individuals carrying an expansion based on known pedigree information. Penetrance is calculated as a number of affected individuals divided by the sum of cumulative age-related risks of relatives being affected by 80 years.

RESULTS: This method allows family-specific penetrance to be estimated from family history and at-risk relatives' personalised age-related ALS/FTD risks to be calculated and illustrated graphically. Penetrance reduces as the number and age of at-risk unaffected relatives increases.

CONCLUSIONS: Family history remains the best indicator of penetrance in C9orf72 expansion carriers. Calculating family-specific penetrance can aid genetic counselling by allowing at-risk relatives a more accurate understanding of their individual risk.}, } @article {pmid39315308, year = {2024}, author = {Abati, E and Gagliardi, D and Manini, A and Del Bo, R and Ronchi, D and Meneri, M and Beretta, F and Sarno, A and Rizzo, F and Monfrini, E and Di Fonzo, A and Pellecchia, MT and Brusati, A and Silani, V and Comi, GP and Ratti, A and Verde, F and Ticozzi, N and Corti, S}, title = {Investigating the prevalence of MFN2 mutations in amyotrophic lateral sclerosis: insights from an Italian cohort.}, journal = {Brain communications}, volume = {6}, number = {5}, pages = {fcae312}, pmid = {39315308}, issn = {2632-1297}, abstract = {The MFN2 gene encodes mitofusin 2, a key protein for mitochondrial fusion, transport, maintenance and cell communication. MFN2 mutations are primarily linked to Charcot-Marie-Tooth disease type 2A. However, a few cases of amyotrophic lateral sclerosis and amyotrophic lateral sclerosis/frontotemporal dementia phenotypes with concomitant MFN2 mutations have been previously reported. This study examines the clinical and genetic characteristics of an Italian cohort of amyotrophic lateral sclerosis patients with rare, non-synonymous MFN2 mutations. A group of patients (n = 385) diagnosed with amyotrophic lateral sclerosis at our Neurology Units between 2008 and 2023 underwent comprehensive molecular testing, including MFN2. After excluding pathogenic mutations in the main amyotrophic lateral sclerosis-related genes (i.e. C9orf72, SOD1, FUS and TARDBP), MFN2 variants were classified based on the American College of Medical Genetics and Genomics guidelines, and demographic and clinical data of MFN2-mutated patients were retrieved. We identified 12 rare, heterozygous, non-synonymous MFN2 variants in 19 individuals (4.9%). Eight of these variants, carried by nine patients (2.3%), were either pathogenic, likely pathogenic or variants of unknown significance according to the American College of Medical Genetics and Genomics guidelines. Among these patients, four exhibited a familial pattern of inheritance. The observed phenotypes included classic and bulbar amyotrophic lateral sclerosis, amyotrophic lateral sclerosis/frontotemporal dementia, flail arm, flail leg and progressive muscular atrophy. Median survival after disease onset was extremely variable, ranging from less than 1 to 13 years. This study investigates the prevalence of rare, non-synonymous MFN2 variants within an Italian cohort of amyotrophic lateral sclerosis patients, who have been extensively investigated, enhancing our knowledge of the underlying phenotypic spectrum. Further research is needed to understand whether MFN2 mutations contribute to motor neuron disease and to what extent. Improving our knowledge regarding the genetic basis of amyotrophic lateral sclerosis is crucial both in a diagnostic and therapeutic perspective.}, } @article {pmid39315251, year = {2024}, author = {Maitra, S and Baek, M and Choe, YJ and Kim, NC}, title = {FDA-approved PDE4 inhibitors alleviate the dominant toxicity of ALS-FTD-associated CHCHD10S59L by reducing the PINK1/Parkin pathway.}, journal = {Research square}, volume = {}, number = {}, pages = {}, pmid = {39315251}, issn = {2693-5015}, support = {R56 NS112296/NS/NINDS NIH HHS/United States ; }, abstract = {BACKGROUND: Mutations in coiled-coil-helix-coiled-coil-helix domain containing 10 (CHCHD10) have been identified as a genetic cause of amyotrophic lateral sclerosis and/or frontotemporal dementia(ALS-FTD). In our previous studies using in vivo Drosophila model expressing CHCHD10[S59L], and human cell models expressing CHCHD10[S59L], we have identified that the PINK1/Parkin pathway is activated and causes cellular toxicity. Furthermore, we demonstrated that pseudo-substrate inhibitors for PINK1 and mitofusin2 agonists mitigated the cellular toxicity of CHCHD10[S59L]. Evidences using in vitro, in vivo genetic, and chemical tools indicate that inhibiting PINK1 would be the most promising treatment for CHCHD10[S59L]-induced diseases.

METHODS: An in vivo human cell culture and in vivo Drosophila models expressing CHCHD10[S59L] mutant were utilized in this study to evaluate the effect of PDE4 inhibitors in PINK-parkin mediated cytotoxicity through immunohistochemical and seahorse assays. Data were analysed using one-way ANOVA and post-hoc Dunnett's test for statistical significance.

RESULTS: We investigated cellular pathways that can modulate the PINK1/Parkin pathway and reduce CHCHD10[S59L]-induced cytotoxicity. Here, we report that FDA-approved PDE4 inhibitors reduced CHCHD10[S59L]-induced morphological and functional mitochondrial defects in human cells and an in vivo Drosophila model expressing C2C10H[S81L]. Multiple PDE4 inhibitors decreased PINK1 accumulation and downstream mitophagy induced by CHCHD10[S59L].

CONCLUSION: These findings suggest that PDE4 inhibitors currently available in the market may be repositioned to treat CHCHD10[S59L]-induced ALS-FTD and possibly other related diseases, and that disease treatment with PDE4 inhibitors should include careful consideration of the PINK1/Parkin pathway, as it is generally recognized as a protective pathway.}, } @article {pmid39314515, year = {2025}, author = {He, D and Wang, X and Hao, M and Shen, D and Yang, X and Liu, M and Li, Y and Wang, J and Cui, L}, title = {Mutational and transcriptional profiling of cuproptosis-associated genes in amyotrophic lateral sclerosis.}, journal = {Genes & diseases}, volume = {12}, number = {1}, pages = {101208}, pmid = {39314515}, issn = {2352-3042}, } @article {pmid39314491, year = {2024}, author = {Guerra San Juan, I and Brunner, J and Eggan, K and Toonen, RF and Verhage, M}, title = {KIF5A regulates axonal repair and time-dependent axonal transport of SFPQ granules and mitochondria in human motor neurons.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {39314491}, issn = {2692-8205}, support = {R01 NS089742/NS/NINDS NIH HHS/United States ; }, abstract = {Mutations in the microtubule binding motor protein, kinesin family member 5A (KIF5A), cause the fatal motor neuron disease, Amyotrophic Lateral Sclerosis. While KIF5 family members transport a variety of cargos along axons, it is still unclear which cargos are affected by KIF5A mutations. We generated KIF5A null mutant human motor neurons to investigate the impact of KIF5A loss on the transport of various cargoes and its effect on motor neuron function at two different timepoints in vitro. The absence of KIF5A resulted in reduced neurite complexity in young motor neurons (DIV14) and significant defects in axonal regeneration capacity at all developmental stages. KIF5A loss did not affect neurofilament transport but resulted in decreased mitochondria motility and anterograde speed at DIV42. More prominently, KIF5A depletion strongly reduced anterograde transport of SFPQ-associated RNA granules in DIV42 motor neuron axons. We conclude that KIF5A most prominently functions in human motor neurons to promote axonal regrowth after injury as well as to anterogradely transport mitochondria and, to a larger extent, SFPQ-associated RNA granules in a time-dependent manner.}, } @article {pmid39314333, year = {2024}, author = {Guha, A and Si, Y and Smith, R and Kazamel, M and Jiang, N and Smith, KA and Thalacker-Mercer, A and Singh, BK and Ho, R and Andrabi, SA and Pereira, JDTDS and Salgado, JS and Agrawal, M and Velic, EH and King, PH}, title = {The myokine FGF21 associates with enhanced survival in ALS and mitigates stress-induced cytotoxicity.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {39314333}, issn = {2692-8205}, support = {I01 BX002466/BX/BLRD VA/United States ; I01 BX006231/BX/BLRD VA/United States ; R01 NS092651/NS/NINDS NIH HHS/United States ; R21 NS111275/NS/NINDS NIH HHS/United States ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is an age-related and fatal neurodegenerative disease characterized by progressive muscle weakness. There is marked heterogeneity in clinical presentation, progression, and pathophysiology with only modest treatments to slow disease progression. Molecular markers that provide insight into this heterogeneity are crucial for clinical management and identification of new therapeutic targets. In a prior muscle miRNA sequencing investigation, we identified altered FGF pathways in ALS muscle, leading us to investigate FGF21. We analyzed human ALS muscle biopsy samples and found a large increase in FGF21 expression with localization to atrophic myofibers and surrounding endomysium. A concomitant increase in FGF21 was detected in ALS spinal cords which correlated with muscle levels. FGF21 was increased in the SOD1[G93A] mouse beginning in presymptomatic stages. In parallel, there was dysregulation of the co-receptor, β-Klotho. Plasma FGF21 levels were increased and high levels correlated with slower disease progression, prolonged survival, and increased body mass index. In NSC-34 motor neurons and C2C12 muscle cells expressing SOD1[G93A] or exposed to oxidative stress, ectopic FGF21 mitigated loss of cell viability. In summary, FGF21 is a novel biomarker in ALS that correlates with slower disease progression and exerts trophic effects under conditions of cellular stress.}, } @article {pmid39314138, year = {2025}, author = {Lv, Y and Li, H}, title = {Blood diagnostic and prognostic biomarkers in amyotrophic lateral sclerosis.}, journal = {Neural regeneration research}, volume = {20}, number = {9}, pages = {2556-2570}, pmid = {39314138}, issn = {1673-5374}, abstract = {Amyotrophic lateral sclerosis is a devastating neurodegenerative disease for which the current treatment approaches remain severely limited. The principal pathological alterations of the disease include the selective degeneration of motor neurons in the brain, brainstem, and spinal cord, as well as abnormal protein deposition in the cytoplasm of neurons and glial cells. The biological markers under extensive scrutiny are predominantly located in the cerebrospinal fluid, blood, and even urine. Among these biomarkers, neurofilament proteins and glial fibrillary acidic protein most accurately reflect the pathologic changes in the central nervous system, while creatinine and creatine kinase mainly indicate pathological alterations in the peripheral nerves and muscles. Neurofilament light chain levels serve as an indicator of neuronal axonal injury that remain stable throughout disease progression and are a promising diagnostic and prognostic biomarker with high specificity and sensitivity. However, there are challenges in using neurofilament light chain to differentiate amyotrophic lateral sclerosis from other central nervous system diseases with axonal injury. Glial fibrillary acidic protein predominantly reflects the degree of neuronal demyelination and is linked to non-motor symptoms of amyotrophic lateral sclerosis such as cognitive impairment, oxygen saturation, and the glomerular filtration rate. TAR DNA-binding protein 43, a pathological protein associated with amyotrophic lateral sclerosis, is emerging as a promising biomarker, particularly with advancements in exosome-related research. Evidence is currently lacking for the value of creatinine and creatine kinase as diagnostic markers; however, they show potential in predicting disease prognosis. Despite the vigorous progress made in the identification of amyotrophic lateral sclerosis biomarkers in recent years, the quest for definitive diagnostic and prognostic biomarkers remains a formidable challenge. This review summarizes the latest research achievements concerning blood biomarkers in amyotrophic lateral sclerosis that can provide a more direct basis for the differential diagnosis and prognostic assessment of the disease beyond a reliance on clinical manifestations and electromyography findings.}, } @article {pmid39313512, year = {2024}, author = {Khan, AF and Iturria-Medina, Y}, title = {Beyond the usual suspects: multi-factorial computational models in the search for neurodegenerative disease mechanisms.}, journal = {Translational psychiatry}, volume = {14}, number = {1}, pages = {386}, pmid = {39313512}, issn = {2158-3188}, mesh = {Humans ; *Neurodegenerative Diseases/diagnostic imaging/physiopathology ; *Neuroimaging/methods ; *Brain/diagnostic imaging/physiopathology ; Disease Progression ; Biomarkers ; Alzheimer Disease/diagnostic imaging/physiopathology ; Computer Simulation ; }, abstract = {From Alzheimer's disease to amyotrophic lateral sclerosis, the molecular cascades underlying neurodegenerative disorders remain poorly understood. The clinical view of neurodegeneration is confounded by symptomatic heterogeneity and mixed pathology in almost every patient. While the underlying physiological alterations originate, proliferate, and propagate potentially decades before symptomatic onset, the complexity and inaccessibility of the living brain limit direct observation over a patient's lifespan. Consequently, there is a critical need for robust computational methods to support the search for causal mechanisms of neurodegeneration by distinguishing pathogenic processes from consequential alterations, and inter-individual variability from intra-individual progression. Recently, promising advances have been made by data-driven spatiotemporal modeling of the brain, based on in vivo neuroimaging and biospecimen markers. These methods include disease progression models comparing the temporal evolution of various biomarkers, causal models linking interacting biological processes, network propagation models reproducing the spatial spreading of pathology, and biophysical models spanning cellular- to network-scale phenomena. In this review, we discuss various computational approaches for integrating cross-sectional, longitudinal, and multi-modal data, primarily from large observational neuroimaging studies, to understand (i) the temporal ordering of physiological alterations, i(i) their spatial relationships to the brain's molecular and cellular architecture, (iii) mechanistic interactions between biological processes, and (iv) the macroscopic effects of microscopic factors. We consider the extents to which computational models can evaluate mechanistic hypotheses, explore applications such as improving treatment selection, and discuss how model-informed insights can lay the groundwork for a pathobiological redefinition of neurodegenerative disorders.}, } @article {pmid39313484, year = {2025}, author = {Funai, A and Hayashi, K and Kawata, A and Nakayama, Y and Matsuda, C and Haraguchi, M and Takahashi, K and Komori, T}, title = {An autopsy report of a long-survival case of familial amyotrophic lateral sclerosis with SOD1 G93S gene mutation: Lack of SOD1-positive inclusion in the remaining neurons.}, journal = {Neuropathology : official journal of the Japanese Society of Neuropathology}, volume = {45}, number = {1}, pages = {60-65}, doi = {10.1111/neup.13004}, pmid = {39313484}, issn = {1440-1789}, support = {22H03398//Japan Society for the Promotion of Science/ ; }, mesh = {Humans ; Male ; Aged ; *Amyotrophic Lateral Sclerosis/enzymology/genetics ; *Superoxide Dismutase-1/genetics ; Fatal Outcome ; Autopsy ; *Mutation/genetics ; Time Factors ; *Motor Neurons/enzymology ; }, abstract = {We describe the case of a 70-year-old Japanese man with familial amyotrophic lateral sclerosis (fALS) associated with a p.Gly93Ser mutation in the copper/zinc superoxide dismutase (SOD1) gene. This mutation is one of the relatively rare SOD1 mutations, with only one previous autopsy report, and is known for its longer disease duration. As previously reported, the patient had weakness in the lower limbs at age 33, followed by dysphagia, dysesthesia in the lower limbs, and autonomic dysfunction. He required mechanical ventilation at age 44 and died of acute pancreatitis at age 70. Neuropathologically, multisystem degeneration was observed beyond lesions typical of familial ALS with posterior column involvement. In addition, there was no SOD1-positive inclusion in the remaining motor neurons. The absence of SOD1-positive inclusion is a rare feature observed predominantly in long survival cases with SOD1 gene mutations. We hypothesize that the considerably lower amount of abnormal SOD1 protein in the motor neuron cells might explain our patient's extraordinarily long clinical course.}, } @article {pmid39313211, year = {2025}, author = {Rahimi, M and Al Masry, Z and Templeton, JM and Schneider, S and Poellabauer, C}, title = {A Comprehensive Multifunctional Approach for Measuring Parkinson's Disease Severity.}, journal = {Applied clinical informatics}, volume = {16}, number = {1}, pages = {11-23}, pmid = {39313211}, issn = {1869-0327}, mesh = {Humans ; *Parkinson Disease/diagnosis/physiopathology ; Male ; Female ; *Severity of Illness Index ; Aged ; Middle Aged ; Neuropsychological Tests ; Machine Learning ; }, abstract = {OBJECTIVES: This research study aims to advance the staging of Parkinson's disease (PD) by incorporating machine learning to assess and include a broader multifunctional spectrum of neurocognitive symptoms in the staging schemes beyond motor-centric assessments. Specifically, we provide a novel framework to modernize and personalize PD staging more objectively by proposing a hybrid feature scoring approach.

METHODS:  We recruited 37 individuals diagnosed with PD, each of whom completed a series of tablet-based neurocognitive tests assessing motor, memory, speech, executive functions, and tasks ranging in complexity from single to multifunctional. Then, the collected data were used to develop a hybrid feature scoring system to calculate a weighted vector for each function. We evaluated the current PD staging schemes and developed a new approach based on the features selected and extracted using random forest and principal component analysis.

RESULTS:  Our findings indicate a substantial bias in current PD staging systems toward fine motor skills, that is, other neurological functions (memory, speech, executive function, etc.) do not map into current PD stages as well as fine motor skills do. The results demonstrate that a more accurate and personalized assessment of PD severity could be achieved by including a more exhaustive range of neurocognitive functions in the staging systems either by involving multiple functions in a unified staging score or by designing a function-specific staging system.

CONCLUSION:  The proposed hybrid feature score approach provides a comprehensive understanding of PD by highlighting the need for a staging system that covers various neurocognitive functions. This approach could potentially lead to more effective, objective, and personalized treatment strategies. Further, this proposed methodology could be adapted to other neurodegenerative conditions such as Alzheimer's disease or amyotrophic lateral sclerosis.}, } @article {pmid39312574, year = {2024}, author = {Plessis-Belair, J and Ravano, K and Han, E and Janniello, A and Molina, C and Sher, RB}, title = {NEMF mutations in mice illustrate how Importin-β specific nuclear transport defects recapitulate neurodegenerative disease hallmarks.}, journal = {PLoS genetics}, volume = {20}, number = {9}, pages = {e1011411}, pmid = {39312574}, issn = {1553-7404}, support = {R01 AG079898/AG/NIA NIH HHS/United States ; }, mesh = {Animals ; *beta Karyopherins/metabolism/genetics ; *Active Transport, Cell Nucleus/genetics ; Mice ; Humans ; *Neurodegenerative Diseases/genetics/metabolism/pathology ; *Disease Models, Animal ; Mutation ; ran GTP-Binding Protein/metabolism/genetics ; Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology ; Cell Nucleus/metabolism/genetics ; Frontotemporal Dementia/genetics/metabolism/pathology ; Frontotemporal Lobar Degeneration/genetics/metabolism/pathology ; Alzheimer Disease/genetics/metabolism/pathology ; }, abstract = {Pathological disruption of Nucleocytoplasmic Transport (NCT), such as the mis-localization of nuclear pore complex proteins (Nups), nuclear transport receptors, Ran-GTPase, and RanGAP1, are seen in both animal models and in familial and sporadic forms of amyotrophic lateral sclerosis (ALS), frontal temporal dementia and frontal temporal lobar degeneration (FTD\FTLD), and Alzheimer's and Alzheimer's Related Dementias (AD/ADRD). However, the question of whether these alterations represent a primary cause, or a downstream consequence of disease is unclear, and what upstream factors may account for these defects are unknown. Here, we report four key findings that shed light on the upstream causal role of Importin-β-specific nuclear transport defects in disease onset. First, taking advantage of two novel mouse models of NEMF neurodegeneration (NemfR86S and NemfR487G) that recapitulate many cellular and biochemical aspects of neurodegenerative diseases, we find an Importin-β-specific nuclear import block. Second, we observe cytoplasmic mis-localization and aggregation of multiple proteins implicated in the pathogenesis of ALS/FTD and AD/ADRD, including TDP43, Importin-β, RanGap1, and Ran. These findings are further supported by a pathological interaction between Importin-β and the mutant NEMFR86S protein in cytoplasmic accumulations. Third, we identify similar transcriptional dysregulation in key genes associated with neurodegenerative disease. Lastly, we show that even transient pharmaceutical inhibition of Importin-β in both mouse and human neuronal and non-neuronal cells induces key proteinopathies and transcriptional alterations seen in our mouse models and in neurodegeneration. Our convergent results between mouse and human neuronal and non-neuronal cellular biology provide mechanistic evidence that many of the mis-localized proteins and dysregulated transcriptional events seen in multiple neurodegenerative diseases may in fact arise primarily from a primary upstream defect in Importin- β nuclear import. These findings have critical implications for investigating how sporadic forms of neurodegeneration may arise from presently unidentified genetic and environmental perturbations in Importin-β function.}, } @article {pmid39312484, year = {2024}, author = {Okada, K and Ito, D and Morimoto, S and Kato, C and Oguma, Y and Warita, H and Suzuki, N and Aoki, M and Kuramoto, J and Kobayashi, R and Shinozaki, M and Ikawa, M and Nakahara, J and Takahashi, S and Nishimoto, Y and Shibata, S and Okano, H}, title = {Multiple lines of evidence for disruption of nuclear lamina and nucleoporins in FUS amyotrophic lateral sclerosis.}, journal = {Brain : a journal of neurology}, volume = {147}, number = {11}, pages = {3933-3948}, pmid = {39312484}, issn = {1460-2156}, support = {21H02812//Japan Society for the Promotion of Science/ ; JP20ek0109395//Japan Agency for Medical Research and Development/ ; //Takeda Science Foundation/ ; //The Yukihiko Miyata Memorial Trust for ALS Research/ ; //Yoshio Koide/ ; //Japan ALS Association/ ; //Daiichi Sankyo Foundation of Life Science/ ; //Keio Medical Association and Keio University Grant-in-Aid for Encouragement of Young Medical Scientists/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology ; Animals ; *RNA-Binding Protein FUS/genetics/metabolism ; Mice ; Humans ; *Nuclear Pore Complex Proteins/genetics/metabolism ; *Motor Neurons/metabolism/pathology ; *Induced Pluripotent Stem Cells/metabolism ; *Nuclear Lamina/metabolism ; Disease Models, Animal ; Male ; Mice, Transgenic ; Spinal Cord/metabolism/pathology ; Female ; Mutation ; }, abstract = {Advanced pathological and genetic approaches have revealed that mutations in fused in sarcoma/translated in liposarcoma (FUS/TLS), which is pivotal for DNA repair, alternative splicing, translation and RNA transport, cause familial amyotrophic lateral sclerosis (ALS). The generation of suitable animal models for ALS is essential for understanding its pathogenesis and developing therapies. Therefore, we used CRISPR-Cas9 to generate FUS-ALS mutation in the non-classical nuclear localization signal (NLS), H517D (mouse position: H509D) and genome-edited mice. Fus WT/H509D mice showed progressive motor impairment (accelerating rotarod and DigiGait system) with age, which was associated with the loss of motor neurons and disruption of the nuclear lamina and nucleoporins and DNA damage in spinal cord motor neurons. We confirmed the validity of our model by showing that nuclear lamina and nucleoporin disruption were observed in lower motor neurons differentiated from patient-derived human induced pluripotent stem cells (hiPSC-LMNs) with FUS-H517D and in the post-mortem spinal cord of patients with ALS. RNA sequence analysis revealed that most nuclear lamina and nucleoporin-linking genes were significantly decreased in FUS-H517D hiPSC-LMNs. This evidence suggests that disruption of the nuclear lamina and nucleoporins is crucial for ALS pathomechanisms. Combined with patient-derived hiPSC-LMNs and autopsy samples, this mouse model might provide a more reliable understanding of ALS pathogenesis and might aid in the development of therapeutic strategies.}, } @article {pmid39311426, year = {2024}, author = {Azzolino, D and Piras, R and Zulueta, A and Lucchi, T and Lunetta, C}, title = {Amyotrophic lateral sclerosis as a disease model of sarcopenia.}, journal = {Age and ageing}, volume = {53}, number = {9}, pages = {}, doi = {10.1093/ageing/afae209}, pmid = {39311426}, issn = {1468-2834}, mesh = {Humans ; *Sarcopenia/physiopathology/diagnosis ; *Amyotrophic Lateral Sclerosis/physiopathology/complications/diagnosis ; *Muscle, Skeletal/pathology/physiopathology ; Aging/pathology ; Animals ; Age Factors ; Aged ; Risk Factors ; }, abstract = {Sarcopenia, the progressive decline of muscle mass and function, has traditionally been viewed as an age-related process leading to a broad range of adverse outcomes. However, it has been widely reported that sarcopenia can occur earlier in life in association with various conditions (i.e. disease-related sarcopenia), including neuromuscular disorders. As early as 2010, the European Working Group on Sarcopenia in Older People included neurodegenerative diseases characterised by motor neuron loss among the mechanisms underlying sarcopenia. Despite some differences in pathogenetic mechanisms, both amyotrophic lateral sclerosis (ALS) and age-related sarcopenia share common characteristics, such as the loss of motor units and muscle fibre atrophy, oxidative stress, mitochondrial dysfunction and inflammation. The histology of older muscle shows fibre size heterogeneity, fibre grouping and a loss of satellite cells, similar to what is observed in ALS patients. Regrettably, the sarcopenic process in ALS patients has been largely overlooked, and literature on the condition in this patient group is very scarce. Some instruments used for the assessment of sarcopenia in older people could also be applied to ALS patients. At this time, there is no approved specific pharmacological treatment to reverse damage to motor neurons or cure ALS, just as there is none for sarcopenia. However, some agents targeting the muscle, like myostatin and mammalian target of rapamycin inhibitors, are under investigation both in the sarcopenia and ALS context. The development of new therapeutic agents targeting the skeletal muscle may indeed be beneficial to both ALS patients and older people with sarcopenia.}, } @article {pmid39311315, year = {2025}, author = {Ortiz-Corredor, F and Correa-Arrieta, C and Forero Diaz, JJ and Castellar-Leones, S and Gil-Salcedo, A}, title = {Profiles of disease progression and predictors of mortality in Colombian patients with amyotrophic lateral sclerosis: a comprehensive longitudinal study.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {26}, number = {1-2}, pages = {141-148}, doi = {10.1080/21678421.2024.2405587}, pmid = {39311315}, issn = {2167-9223}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/mortality/diagnosis ; *Disease Progression ; Female ; Colombia/epidemiology ; Male ; Middle Aged ; Longitudinal Studies ; Retrospective Studies ; Aged ; Prognosis ; Adult ; }, abstract = {OBJECTIVE: This study aimed to assess the prognostic value of the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) in predicting mortality and characterizing disease progression patterns in ALS patients in Colombia.

METHODS: We conducted a retrospective longitudinal analysis of 537 ALS patients from the Roosevelt Institute Rehabilitation Service between October 2008 and October 2022. The study excluded nine patients due to incomplete data, resulting in 528 individuals in the analysis. ALS diagnoses were confirmed using the revised El Escorial and Gold Coast criteria. Disease progression was assessed using the ALSFRS-R, and mortality data were sourced from follow-up calls and a national database. Statistical analysis included Cox proportional hazards models to identify mortality predictors and Growth Mixture Modeling (GMM) to explore ALS progression trajectories.

RESULTS: The majority of the cohort (63.8%) deceased within the 84-month follow-up period. Survival analysis revealed that each point increase in the ALSFRS-R rate was associated with a 2.22-fold (95% CI =1.99-2.48, p < 0.001) increased risk of mortality. In the population with data from two clinical visits, the ALSFRS-R rate based on initial assessments predicted mortality more effectively over 36 months than the rate based on two evaluations. GMM identified three distinct progression trajectories: slow, intermediate, and rapid decliners.

CONCLUSIONS: The ALSFRS-R rate, derived from self-reported symptom onset, significantly predicts mortality, underscoring its value in clinical assessments. This study highlights the heterogeneity in disease progression among Colombian ALS patients, indicating the necessity for personalized treatment approaches based on individual progression trajectories. Further studies are needed to refine these predictive models and improve patient management and outcomes.}, } @article {pmid39311028, year = {2024}, author = {Driver, MD and Postema, J and Onck, PR}, title = {The Effect of Dipeptide Repeat Proteins on FUS/TDP43-RNA Condensation in C9orf72 ALS/FTD.}, journal = {The journal of physical chemistry. B}, volume = {128}, number = {39}, pages = {9405-9417}, pmid = {39311028}, issn = {1520-5207}, mesh = {*RNA-Binding Protein FUS/chemistry/metabolism/genetics ; *C9orf72 Protein/chemistry/genetics/metabolism ; *Amyotrophic Lateral Sclerosis/genetics/metabolism ; *Dipeptides/chemistry/metabolism ; *RNA/chemistry/metabolism ; Humans ; *Molecular Dynamics Simulation ; *DNA-Binding Proteins/chemistry/metabolism/genetics ; *Frontotemporal Dementia/genetics/metabolism ; }, abstract = {Condensation of RNA binding proteins (RBPs) with RNA is essential for cellular function. The most common familial cause of the diseases ALS and FTD is C9orf72 repeat expansion disorders that produce dipeptide repeat proteins (DPRs). We explore the hypothesis that DPRs disrupt the native condensation behavior of RBPs and RNA through molecular interactions resulting in toxicity. FUS and TDP43 are two RBPs known to be affected in ALS/FTD. We use our previously developed 1-bead-per-amino acid and a newly developed 3-bead-per-nucleotide molecular dynamics model to explore ternary phase diagrams of FUS/TDP43-RNA-DPR systems. We show that the most toxic arginine containing DPRs (R-DPRs) can disrupt the RBP condensates through cation-π interactions and can strongly sequester RNA through electrostatic interactions. The native droplet morphologies are already modified at small additions of R-DPRs leading to non-native FUS/TDP43-encapsulated condensates with a marbled RNA/DPR core.}, } @article {pmid39310990, year = {2024}, author = {Vallejo Herrera, MJ and Vallejo Herrera, V and Del Toro Ortega, A and Tapia Guerrero, MJ}, title = {[Radiological versus endoscopic gastrostomy in patients with amyotrophic lateral sclerosis].}, journal = {Nutricion hospitalaria}, volume = {41}, number = {6}, pages = {1160-1164}, doi = {10.20960/nh.05190}, pmid = {39310990}, issn = {1699-5198}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/complications/therapy ; *Gastrostomy/methods/adverse effects ; Middle Aged ; Retrospective Studies ; Male ; Female ; *Enteral Nutrition/methods ; Aged ; Deglutition Disorders/etiology ; Adult ; Treatment Outcome ; Radiography ; }, abstract = {IIntroduction: patients with amyotrophic lateral sclerosis (ALS) require nutritional support, in most cases with enteral nutrition through gastrostomy, either endoscopic (PEG) or radiological (PRG). Objectives: to analyze the characteristics of patients with ALS at the time of PEG/PRG placement, and to compare the efficacy and safety of PRG versus PEG. Methods: a retrospective descriptive study. All patients with ALS who required gastrostomy in the last 3 years (2021-2023) in our hospital were recruited (4 PEG and 6 PRG). Demographic and nutritional parameters were analyzed. Results: ten patients were included, with an average age of 57 years. All patients presented with dysphagia and received oral or tube supplements prior to gastrostomy placement. The average duration of enteral nutrition was approximately 50 months, with a mortality rate of 30 % at 12 months after gastrostomy. The success rate of PEG and PRG was similar, with no complications. All patients developed deterioration of respiratory function, even after nutritional support. Conclusion: gastrostomy should be indicated as soon as a patient is at risk of aspiration pneumonia or when weight loss begins. Although the nutritional benefit of gastrostomy is well established, there is currently a delay between diagnosis and placement of approximately 4 years. PRG appears to be safer than PEG in patients with ALS and respiratory failure.}, } @article {pmid39310519, year = {2024}, author = {Albadawi, EA}, title = {Microstructural Changes in the Corpus Callosum in Neurodegenerative Diseases.}, journal = {Cureus}, volume = {16}, number = {8}, pages = {e67378}, pmid = {39310519}, issn = {2168-8184}, abstract = {The corpus callosum, the largest white matter structure in the brain, plays a crucial role in interhemispheric communication and cognitive function. This review examines the microstructural changes observed in the corpus callosum across various neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis (ALS). New neuroimaging studies, mainly those that use diffusion tensor imaging (DTI) and advanced tractography methods, were put together to show how changes have happened in the organization of white matter and the connections between them. Some of the most common ways the corpus callosum breaks down are discussed, including less fractional anisotropy, higher mean diffusivity, and atrophy in certain regions. The relationship between these microstructural changes and cognitive decline, motor dysfunction, and disease progression is explored. Additionally, we consider the potential of corpus callosum imaging as a biomarker for early disease detection and monitoring. Studies show that people with these disorders have lower fractional anisotropy and higher mean diffusivity in the corpus callosum, often in ways that are specific to the disease. These changes often happen before gray matter atrophy and are linked to symptoms, which suggests that the corpus callosum could be used as an early sign of neurodegeneration. The review also highlights the implications of these findings for understanding disease mechanisms and developing therapeutic strategies. Future directions, including the application of advanced imaging techniques and longitudinal studies, are discussed to elucidate the role of corpus callosum degeneration in neurodegenerative processes. This review underscores the importance of the corpus callosum in understanding the pathophysiology of neurodegenerative diseases and its potential as a target for therapeutic interventions.}, } @article {pmid39307464, year = {2024}, author = {Kalykaki, M and Rubio-Tomás, T and Tavernarakis, N}, title = {The role of mitochondria in cytokine and chemokine signalling during ageing.}, journal = {Mechanisms of ageing and development}, volume = {222}, number = {}, pages = {111993}, doi = {10.1016/j.mad.2024.111993}, pmid = {39307464}, issn = {1872-6216}, mesh = {Humans ; *Mitochondria/metabolism ; *Aging/metabolism ; *Signal Transduction ; *Inflammation/metabolism ; *Cytokines/metabolism ; Animals ; Chemokines/metabolism ; Cellular Senescence/physiology ; }, abstract = {Ageing is accompanied by a persistent, low-level inflammation, termed "inflammageing", which contributes to the pathogenesis of age-related diseases. Mitochondria fulfil multiple roles in host immune responses, while mitochondrial dysfunction, a hallmark of ageing, has been shown to promote chronic inflammatory states by regulating the production of cytokines and chemokines. In this review, we aim to disentangle the molecular mechanisms underlying this process. We describe the role of mitochondrial signalling components such as mitochondrial DNA, mitochondrial RNA, N-formylated peptides, ROS, cardiolipin, cytochrome c, mitochondrial metabolites, potassium efflux and mitochondrial calcium in the age-related immune system activation. Furthermore, we discuss the effect of age-related decline in mitochondrial quality control mechanisms, including mitochondrial biogenesis, dynamics, mitophagy and UPR[mt], in inflammatory states upon ageing. In addition, we focus on the dynamic relationship between mitochondrial dysfunction and cellular senescence and its role in regulating the secretion of pro-inflammatory molecules by senescent cells. Finally, we review the existing literature regarding mitochondrial dysfunction and inflammation in specific age-related pathological conditions, including neurodegenerative diseases (Alzheimer's and Parkinson's disease, and amyotrophic lateral sclerosis), osteoarthritis and sarcopenia.}, } @article {pmid39307005, year = {2024}, author = {Austin, JM and Bailey, R and Velazquez, SG and Sainath, H and Jackson, C}, title = {Clinical effectiveness of medical marijuana in patients with amyotrophic lateral sclerosis.}, journal = {Journal of the neurological sciences}, volume = {466}, number = {}, pages = {123243}, doi = {10.1016/j.jns.2024.123243}, pmid = {39307005}, issn = {1878-5883}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy/complications ; *Medical Marijuana/therapeutic use ; Male ; Female ; Middle Aged ; Retrospective Studies ; Aged ; Treatment Outcome ; Disease Progression ; Cohort Studies ; Adult ; Anxiety/drug therapy/etiology ; }, abstract = {Following legalization, Medical Marijuana (MM), has been used to treat the symptoms of Amyotrophic Lateral Sclerosis (ALS), yet data regarding Medical Marijuana's efficacy is lacking. Thus, we conducted a retrospective cohort study to assess Medical Marijuana's impact on ALS symptoms and progression. We reviewed the charts of all ALS patients treated in our clinic over a two-year period to collect data related to the primary outcome measures of symptoms of pain, poor appetite, anxiety, spasticity, insomnia, ALSFRS-R score, BMI, and MM use. Two groups were defined: a control group with target symptoms but no MM prescription, and a test group that filled a MM prescription, including a subgroup on MM for ≥3 visits. Outcomes were correlations between MM usage and symptom prevalence, and between MM usage and BMI and ALSFRS-R decline slope, analyzed using descriptive statistics and qualitative analysis via local regression. Data included 344 ALS patients. We found MM use correlated with alleviation of pain, poor appetite, and anxiety in the short term, but not with spasticity or insomnia. There was no correlation between MM use BMI maintenance. Notably, MM usage correlated with faster ALS progression, although patients using MM exhibited higher symptom burden and progressed faster than controls even pre-MM prescription. In conclusion, MM shows correlation with managing pain, poor appetite, and short-term anxiety in ALS, but is also correlated with faster disease progression based on ALSFRS-R scores. We suggest a multi-center, randomized controlled trial to evaluate both the clinical efficacy and safety of MM in the treatment of ALS.}, } @article {pmid39305776, year = {2024}, author = {Lichtfouse, J and Courtier, A and Vergunst, AC and Giannoni, P}, title = {Effects of environmental concentrations of toxins BMAA and its isomers DAB and AEG on zebrafish larvae.}, journal = {Ecotoxicology and environmental safety}, volume = {285}, number = {}, pages = {117045}, doi = {10.1016/j.ecoenv.2024.117045}, pmid = {39305776}, issn = {1090-2414}, mesh = {Animals ; *Zebrafish ; *Amino Acids, Diamino/toxicity ; *Cyanobacteria Toxins ; *Water Pollutants, Chemical/toxicity ; *Larva/drug effects ; Aminobutyrates/toxicity ; Glycine/toxicity/analogs & derivatives ; Embryo, Nonmammalian/drug effects ; Toxicity Tests, Acute ; Embryonic Development/drug effects ; Isomerism ; }, abstract = {The increasing concern over the environmental presence of β-N-Methylamino-L-alanine (BMAA), a toxin primarily produced by cyanobacteria and diatoms, has stimulated numerous studies to evaluate the risk for exposed populations, mainly aquatic organisms and humans. This study focuses on the toxicity of environmental concentrations of BMAA and its isomers, l-2,4 diaminobutyric acid dihydrochloride (DAB) and N-(2-aminoethyl) glycine (AEG) on zebrafish embryo development (ng.L[-1]). Presence of BMAA in various environments, including aquatic sources, air, and desert crusts, has raised concerns due to its potential link to neurodegenerative diseases such as the amyotrophic lateral sclerosis/parkinsonism dementia complex (ALS/PDC). Despite its known toxicity at high concentrations, there is limited information on the effects of environmental concentrations of BMAA and its isomers. These isomers are often found in association with BMAA and have been detected in seafood intended for human consumption, indicating potential risks from bioaccumulation and biomagnification. Zebrafish embryos have been chosen as a model due to their relevance for embryonic development and toxicity studies. The study employed fish embryo acute toxicity tests and behavioural analyses to specifically assess the sublethal effects of BMAA, DAB, and AEG. The results demonstrated larval mortality rates between 0 % and 3.75 %, while morphological defects were detected across all tested concentrations for each molecule. Behavioural analyses showed alterations in swimming behaviour. Unexpectedly, the changes in morphology and locomotion of the zebrafish larvae were detected more frequently at the lowest concentrations tested, suggesting potential non-monotonic dose responses. Overall, this research underscores the environmental risks associated with BMAA and its isomers, highlighting the importance of continuous monitoring and understanding of their sublethal effects on aquatic organisms and potential implications for human health. Further studies are warranted to elucidate the mechanisms of toxicity, evaluate long-term effects, and assess the risks associated with chronic exposure to these toxins.}, } @article {pmid39297678, year = {2024}, author = {Paoletti, O and Hyeraci, G and Finochietti, M and Celani, MG and Bacigalupo, I and Lombardi, N and Crescioli, G and Tuccori, M and Cascini, S and Gini, R and Addis, A and Kirchmayer, U and , }, title = {Pharmacological and non-pharmacological treatments in amyotrophic lateral sclerosis: an Italian real-world data study.}, journal = {European journal of neurology}, volume = {31}, number = {12}, pages = {e16470}, pmid = {39297678}, issn = {1468-1331}, support = {//Agenzia Italiana del Farmaco, Ministero della Salute/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy/epidemiology/drug therapy ; Italy/epidemiology ; *Riluzole/therapeutic use ; Female ; Male ; Aged ; Middle Aged ; Neuroprotective Agents/therapeutic use ; }, abstract = {BACKGROUND AND PURPOSE: The purpose was to describe the use patterns of pharmacological and non-pharmacological therapies and investigate potential determinants of riluzole use in patients newly diagnosed with amyotrophic lateral sclerosis (ALS) in three Italian regions.

METHODS: Amyotrophic lateral sclerosis patients were selected from administrative healthcare databases of Latium, Tuscany and Umbria from 1 January 2014 to 31 December 2019 based on hospital- and disease-specific co-payment exemption data. The first trace of ALS was considered the index date. Incident ALS cases were those without a trace of ALS during the 3-year look back. Patients were described in terms of demographics, clinical characteristics and drug use at baseline, and were classified into four categories based on riluzole use in the 2 years before and 1 year after the index date: prevalent, incident, former users and non-users. Use of symptomatic pharmacological and non-pharmacological therapies was described across these categories during 12 months after the index date. Determinants of riluzole use were also investigated.

RESULTS AND CONCLUSIONS: A total of 1636 ALS incident subjects were detected in the three regions, mainly aged 65-74 years. Patients were generally fragile with a high prevalence of comorbidities at baseline. Riluzole was used by 27.4% of the overall study cohort at baseline and steeply increased in the first year after the index date differently between regions (Latium 61.2%, Tuscany 85.0%, Umbria 76.5%), with about half of the subjects being incident users. In the 12 months after the index date, also symptomatic therapies increased, in riluzole users and non-users. Determinants analysis showed that higher patient severity and complexity were associated with a lower likelihood of being treated with riluzole.}, } @article {pmid39297377, year = {2024}, author = {Akyuz, E and Aslan, FS and Gokce, E and Ilmaz, O and Topcu, F and Kakac, S}, title = {Extracellular vesicle and CRISPR gene therapy: Current applications in Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease.}, journal = {The European journal of neuroscience}, volume = {60}, number = {8}, pages = {6057-6090}, doi = {10.1111/ejn.16541}, pmid = {39297377}, issn = {1460-9568}, mesh = {Humans ; *Genetic Therapy/methods ; *Extracellular Vesicles/metabolism/genetics ; *CRISPR-Cas Systems ; *Huntington Disease/therapy/genetics ; *Amyotrophic Lateral Sclerosis/genetics/therapy ; *Parkinson Disease/therapy/genetics ; *Alzheimer Disease/therapy/genetics ; Animals ; Gene Editing/methods ; Neurodegenerative Diseases/therapy/genetics ; }, abstract = {Neurodegenerative diseases are characterized by progressive deterioration of the nervous system. Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD) are prominently life-threatening examples of neurodegenerative diseases. The complexity of the pathophysiology in neurodegenerative diseases causes difficulties in diagnosing. Although the drugs temporarily help to correct specific symptoms including memory loss and degeneration, a complete treatment has not been found yet. New therapeutic approaches have been developed to understand and treat the underlying pathogenesis of neurodegenerative diseases. With this purpose, clustered-regularly interspaced short palindromic repeats/CRISPR-associated protein (CRISPR/Cas) technology has recently suggested a new treatment option. Editing of the genome is carried out by insertion and deletion processes on DNA. Safe delivery of the CRISPR/Cas system to the targeted cells without affecting surrounding cells is frequently investigated. Extracellular vesicles (EVs), that is exosomes, have recently been used in CRISPR/Cas studies. In this review, CRISPR/Cas and EV approaches used for diagnosis and/or treatment in AD, PD, ALS, and HD are reviewed. CRISPR/Cas and EV technologies, which stand out as new therapeutic approaches, may offer a definitive treatment option in neurodegenerative diseases.}, } @article {pmid39305312, year = {2024}, author = {Torres, P and Rico-Rios, S and Ceron-Codorniu, M and Santacreu-Vilaseca, M and Seoane-Miraz, D and Jad, Y and Ayala, V and Mariño, G and Beltran, M and Miralles, MP and Andrés-Benito, P and Fernandez-Irigoyen, J and Santamaria, E and López-Otín, C and Soler, RM and Povedano, M and Ferrer, I and Pamplona, R and Wood, MJA and Varela, MA and Portero-Otin, M}, title = {TDP-43 regulates LC3ylation in neural tissue through ATG4B cryptic splicing inhibition.}, journal = {Acta neuropathologica}, volume = {148}, number = {1}, pages = {45}, pmid = {39305312}, issn = {1432-0533}, support = {PI 20-00155//Instituto de Salud Carlos III/ ; 23-00176//Instituto de Salud Carlos III/ ; Programa Margarita Salas//Ministerio de Universidades/ ; SGR//Departament d'Innovació, Universitats i Empresa, Generalitat de Catalunya/ ; Ayuda Unzue//Fundación Luzon/ ; }, mesh = {Animals ; *Autophagy-Related Proteins/metabolism/genetics ; Humans ; *DNA-Binding Proteins/metabolism/genetics ; Mice ; *Microtubule-Associated Proteins/metabolism/genetics ; *Amyotrophic Lateral Sclerosis/metabolism/genetics/pathology ; *Cysteine Endopeptidases/metabolism/genetics ; Male ; Spinal Cord/metabolism/pathology ; Autophagy/physiology ; Mice, Knockout ; RNA Splicing/genetics ; Female ; Mice, Transgenic ; Motor Neurons/metabolism/pathology ; Oligonucleotides, Antisense/pharmacology ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is an adult-onset motor neuron disease with a mean survival time of three years. The 97% of the cases have TDP-43 nuclear depletion and cytoplasmic aggregation in motor neurons. TDP-43 prevents non-conserved cryptic exon splicing in certain genes, maintaining transcript stability, including ATG4B, which is crucial for autophagosome maturation and Microtubule-associated proteins 1A/1B light chain 3B (LC3B) homeostasis. In ALS mice (G93A), Atg4b depletion worsens survival rates and autophagy function. For the first time, we observed an elevation of LC3ylation in the CNS of both ALS patients and atg4b[-/-] mouse spinal cords. Furthermore, LC3ylation modulates the distribution of ATG3 across membrane compartments. Antisense oligonucleotides (ASOs) targeting cryptic exon restore ATG4B mRNA in TARDBP knockdown cells. We further developed multi-target ASOs targeting TDP-43 binding sequences for a broader effect. Importantly, our ASO based in peptide-PMO conjugates show brain distribution post-IV administration, offering a non-invasive ASO-based treatment avenue for neurodegenerative diseases.}, } @article {pmid39305271, year = {2024}, author = {Panzetta, ME and Valdivia, RH}, title = {Akkermansia in the gastrointestinal tract as a modifier of human health.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2406379}, pmid = {39305271}, issn = {1949-0984}, support = {R01 AI142376/AI/NIAID NIH HHS/United States ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; *Akkermansia/physiology ; Animals ; *Gastrointestinal Tract/microbiology ; Gastrointestinal Diseases/microbiology ; }, abstract = {Akkermansia sp are common members of the human gut microbiota. Multiple reports have emerged linking the abundance of A. muciniphila to health benefits and disease risk in humans and animals. This review highlights findings linking Akkermansia species in the gastrointestinal (GI) tract to health outcomes across a spectrum of disorders, encompassing those that affect the digestive, respiratory, urinary, and central nervous systems. The mechanism through which Akkermansia exerts a beneficial versus a detrimental effect on health is likely dependent on the genetic makeup of the host metabolic capacity and immunomodulatory properties of the strain, the competition or cooperation with other members of the host microbiota, as well as synergy with co-administered therapies.}, } @article {pmid39304897, year = {2024}, author = {Ortiz, DA and Peregrín, N and Valencia, M and Vinueza-Gavilanes, R and Marín-Ordovas, E and Ferrero, R and Nicolás, MJ and González-Aseguinolaza, G and Arrasate, M and Aragón, T}, title = {GCN2 inhibition reduces mutant SOD1 clustering and toxicity and delays disease progression in an amyotrophic lateral sclerosis mouse model.}, journal = {Translational neurodegeneration}, volume = {13}, number = {1}, pages = {49}, pmid = {39304897}, issn = {2047-9158}, support = {BFU2017-90043-P//Ministerio de Ciencia e Innovación, Gobierno de España/ ; PID2020-120497RB-I00//Ministerio de Ciencia y Universidades, Gobierno de España/ ; Proyecto Intramural IdisNa 2022//Navarra Institute for Health Research (IdiSNA)/ ; Proyectos I+D, 2017//Fundación para la Investigación Médica Aplicada/ ; AC Predoctoral Fellowship//Fundación para la Investigación Médica Aplicada/ ; 270-2018-922//República de Panamá, Programa de Becas IFARHU-SENACYT/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/genetics/drug therapy ; Animals ; *Disease Progression ; *Disease Models, Animal ; Mice ; *Superoxide Dismutase-1/genetics ; *Mice, Transgenic ; Protein Serine-Threonine Kinases/genetics/antagonists & inhibitors ; Humans ; Mutation/genetics ; }, } @article {pmid39302099, year = {2024}, author = {Haider, R and Shipley, B and Surewicz, K and Hinczewski, M and Surewicz, WK}, title = {Pathological C-terminal phosphomimetic substitutions alter the mechanism of liquid-liquid phase separation of TDP-43 low complexity domain.}, journal = {Protein science : a publication of the Protein Society}, volume = {33}, number = {10}, pages = {e5179}, pmid = {39302099}, issn = {1469-896X}, support = {F30 AG071339/AG/NIA NIH HHS/United States ; F30 AG071339-03/NH/NIH HHS/United States ; T32 GM007250/GM/NIGMS NIH HHS/United States ; T32 NS077888/NH/NIH HHS/United States ; T32 GM007250/NH/NIH HHS/United States ; RF1 AG061797/NH/NIH HHS/United States ; }, mesh = {*DNA-Binding Proteins/chemistry/metabolism/genetics ; Humans ; Phosphorylation ; *Protein Domains ; Molecular Dynamics Simulation ; Amino Acid Substitution ; Liquid-Liquid Extraction ; Phase Separation ; }, abstract = {C-terminally phosphorylated TAR DNA-binding protein of 43 kDa (TDP-43) marks the proteinaceous inclusions that characterize a number of age-related neurodegenerative diseases, including amyotrophic lateral sclerosis, frontotemporal lobar degeneration and Alzheimer's disease. TDP-43 phosphorylation at S403/S404 and (especially) at S409/S410 is, in fact, accepted as a biomarker of proteinopathy. These residues are located within the low complexity domain (LCD), which also drives the protein's liquid-liquid phase separation (LLPS). The impact of phosphorylation at these LCD sites on phase separation of the protein is a topic of great interest, as these post-translational modifications and LLPS are both implicated in proteinopathies. Here, we employed a combination of experimental and simulation-based approaches to explore this question on a phosphomimetic model of the TDP-43 LCD. Our turbidity and fluorescence microscopy data show that phosphomimetic Ser-to-Asp substitutions at residues S403, S404, S409 and S410 alter the LLPS behavior of TDP-43 LCD. In particular, unlike the LLPS of unmodified protein, LLPS of the phosphomimetic variants displays a biphasic dependence on salt concentration. Through coarse-grained modeling, we find that this biphasic salt dependence is derived from an altered mechanism of phase separation, in which LLPS-driving short-range intermolecular hydrophobic interactions are modulated by long-range attractive electrostatic interactions. Overall, this in vitro and in silico study provides a physiochemical foundation for understanding the impact of pathologically relevant C-terminal phosphorylation on the LLPS of TDP-43 in a more complex cellular environment.}, } @article {pmid39302063, year = {2024}, author = {Khanna, RK and Catanese, S and Mortemousque, G and Mureau, N and Emond, P and Pisella, PJ and Blasco, H and Corcia, P}, title = {Exploring amyotrophic lateral sclerosis through the visual system: A systematic review.}, journal = {European journal of neurology}, volume = {31}, number = {12}, pages = {e16475}, pmid = {39302063}, issn = {1468-1331}, mesh = {*Amyotrophic Lateral Sclerosis/physiopathology/diagnosis ; Humans ; Vision Disorders/etiology/physiopathology ; Visual Pathways/physiopathology ; }, abstract = {BACKGROUND AND PURPOSE: The human visual system relies on neural networks throughout the brain that are easily accessible for tests exploring eye structures and movements. Over the past two decades, investigations have been carried out on both afferent and efferent components of the visual system in people with amyotrophic lateral sclerosis (ALS). This approach might represent an innovative biomarker research strategy to better characterise the phenotypic variability of ALS. The purpose of this review was to determine whether exploring the visual system of patients with ALS (pwALS) is an effective strategy.

METHODS: The Medline and Web of science databases were searched for studies with terms relating to ALS and vision. Of 1146 references identified, 43 articles were included.

RESULTS: In this review article, both afferent and efferent components of the visual system were found to be impaired in pwALS in the absence of visual complaint, thereby contributing to the hypothesis that ALS is a multisystem disease with sensory involvement. Of note, some areas of the eye remain unexplored (i.e., tears, and retinal function using electroretinography).

CONCLUSIONS: According to the findings available in the literature, investigating the oculomotor system and exploring the ocular surface could represent two key promising strategies to identify new diagnostic biomarkers in pwALS. Further longitudinal studies are needed to identify relevant indicators of disease progression and response to therapeutic intervention.}, } @article {pmid39301564, year = {2024}, author = {Barnard, J and Hunt, R and Yucel, M and Mazaud, D and Smith, BN and Fanto, M}, title = {Human TDP43 is required for ALS‑related annexin A11 toxicity in Drosophila.}, journal = {Biomedical reports}, volume = {21}, number = {5}, pages = {165}, pmid = {39301564}, issn = {2049-9442}, abstract = {Genomics allows identification of genes and mutations associated with amyotrophic lateral sclerosis (ALS). Mutations in annexin A11 (ANXA11) are responsible for ~1% of all familial ALS and fronto-temporal dementia cases. The present study used the fruit fly, Drosophila melanogaster, to assess the mechanism of toxicity of ANXA11 mutants in residues that are conserved in the fly ANXB11 protein, the closest homolog to human ANXA11. In immune fluorescence, lifespan and negative geotaxis assays ANXA11 mutants, while displaying some degree of alteration in localization and function, did not exert any relevant organism toxicity in Drosophila. However, they showed a specific interaction with human TAR DNA-binding protein (TDP43). The present study illustrated that the ANXA11 mutants interact with human TDP43, but not the fly TAR DNA-binding protein-43 homolog (TBPH) or other ALS-associated genes such as super oxide dismutase 1, to shorten lifespan and increase negative geotaxis defects. This sheds light both on the mechanisms underlying ALS, further elucidating the intricate molecular network implicated in ALS and placing ANXA11 as a key player in its pathology, and on the complexity of using Drosophila as a model organism for researching genes in ALS.}, } @article {pmid39300745, year = {2024}, author = {Guo, Y and Ma, G and Wang, Y and Lin, T and Hu, Y and Zang, T}, title = {Causal associations and shared genetic etiology of neurodegenerative diseases with epigenetic aging and human longevity.}, journal = {Aging cell}, volume = {23}, number = {11}, pages = {e14271}, pmid = {39300745}, issn = {1474-9726}, support = {62371161//National Natural Science Foundation of China/ ; }, mesh = {Humans ; *Longevity/genetics ; *Neurodegenerative Diseases/genetics ; *Epigenesis, Genetic ; *Aging/genetics ; *Genome-Wide Association Study ; Mendelian Randomization Analysis ; }, abstract = {The causative mechanisms underlying the genetic relationships of neurodegenerative diseases with epigenetic aging and human longevity remain obscure. We aimed to detect causal associations and shared genetic etiology of neurodegenerative diseases with epigenetic aging and human longevity. We obtained large-scale genome-wide association study summary statistics data for four measures of epigenetic age (GrimAge, PhenoAge, IEAA, and HannumAge) (N = 34,710), multivariate longevity (healthspan, lifespan, and exceptional longevity) (N = 1,349,462), and for multiple neurodegenerative diseases (N = 6618-482,730), including Lewy body dementia, Alzheimer's disease (AD), Parkinson's disease, amyotrophic lateral sclerosis, and multiple sclerosis. Main analyses were conducted using multiplicative random effects inverse-variance weighted Mendelian randomization (MR), and conditional/conjunctional false discovery rate (cond/conjFDR) approach. Shared genomic loci were functionally characterized to gain biological understanding. Evidence showed that AD patients had 0.309 year less in exceptional longevity (IVW beta = -0.309, 95% CI: -0.38 to -0.24, p = 1.51E-19). We also observed suggestively significant causal evidence between AD and GrimAge age acceleration (IVW beta = -0.10, 95% CI: -0.188 to -0.013, p = 0.02). Following the discovery of polygenic overlap, we identified rs78143120 as shared genomic locus between AD and GrimAge age acceleration, and rs12691088 between AD and exceptional longevity. Among these loci, rs78143120 was novel for AD. In conclusion, we observed that only AD had causal effects on epigenetic aging and human longevity, while other neurodegenerative diseases did not. The genetic overlap between them, with mixed effect directions, suggested complex shared genetic etiology and molecular mechanisms.}, } @article {pmid39302926, year = {2024}, author = {Chung, YM and Hu, CS and Sun, E and Tseng, HC}, title = {Morphological multiparameter filtration and persistent homology in mitochondrial image analysis.}, journal = {PloS one}, volume = {19}, number = {9}, pages = {e0310157}, pmid = {39302926}, issn = {1932-6203}, mesh = {Humans ; *Mitochondria/metabolism/genetics ; *Membrane Transport Proteins/genetics/metabolism ; *Image Processing, Computer-Assisted/methods ; Cell Cycle Proteins/genetics/metabolism ; Transcription Factor TFIIIA/genetics/metabolism ; Mutation ; Software ; }, abstract = {The complexity of branching and curvilinear morphology of a complete mitochondrial network within each cell is challenging to analyze and quantify. To address this challenge, we developed an image analysis technique using persistent homology with a multiparameter filtration framework, combining image processing techniques in mathematical morphology. We show that such filtrations contain both topological and geometric information about complex cellular organelle structures, which allows a software program to extract meaningful features. Using this information, we also develop a connectivity index that describes the morphology of the branching patterns. As proof of concept, we utilize this approach to study how mitochondrial networks are altered by genetic changes in the Optineurin gene. Mutations in the autophagy gene Optineurin (OPTN) are associated with primary open-angle glaucoma (POAG), amyotrophic lateral sclerosis (ALS), and Paget's disease of the bone, but the pathophysiological mechanism is unclear. We utilized the proposed mathematical morphology-based multiparameter filtration and persistent homology approach to analyze and quantitatively compare how changes in the OPTN gene alter mitochondrial structures from their normal interconnected, tubular morphology into scattered, fragmented pieces.}, } @article {pmid39300574, year = {2024}, author = {Ashkaran, F and Seyedalipour, B and Baziyar, P and Hosseinkhani, S}, title = {Mutation/metal deficiency in the "electrostatic loop" enhanced aggregation process in apo/holo SOD1 variants: implications for ALS diseases.}, journal = {BMC chemistry}, volume = {18}, number = {1}, pages = {177}, pmid = {39300574}, issn = {2661-801X}, abstract = {Despite the many mechanisms it has created to prevent unfolding and aggregation of proteins, many diseases are caused by abnormal folding of proteins, which are called misfolding diseases. During this process, proteins undergo structural changes and become stable, insoluble beta-sheet aggregates called amyloid fibrils. Mutations/disruptions in metal ion homeostasis in the ALS-associated metalloenzyme superoxide dismutase (SOD1) reduce conformational stability, consistent with the protein aggregation hypothesis for neurodegenerative diseases. However, the exact mechanism of involvement is not well understood. Hence, to understand the role of mutation/ metal deficiency in SOD1 misfolding and aggregation, we investigated the effects of apo/holo SOD1 variants on structural properties using biophysical/experimental techniques. The MD results support the idea that the mutation/metal deficiency can lead to a change in conformation. The increased content of β-sheet structures in apo/holo SOD1 variants can be attributed to the aggregation tendency, which was confirmed by FTIR spectroscopy and dictionary of secondary structure in proteins (DSSP) results. Thermodynamic studies of GdnHCl showed that metal deficiency/mutation/intramolecular S-S reduction together are required to initiate misfolding/aggregation of SOD1. The results showed that apo/holo SOD1 variants under destabilizing conditions induced amyloid aggregates at physiological pH, which were detected by ThT/ANS fluorescence, as well as further confirmation of amyloid/amorphous species by TEM. This study confirms that mutations in the electrostatic loop of SOD1 lead to structural abnormalities, including changes in hydrophobicity, reduced disulfide bonds, and an increased propensity for protein denaturation. This process facilitates the formation of amyloid/amorphous aggregates ALS-associated.}, } @article {pmid39300421, year = {2024}, author = {Koçkaya, PD and Alvur, TM and Odabaşı, O}, title = {Empowering medical students: bridging gaps with high-fidelity simulations; a mixed-methods study on self-efficacy.}, journal = {BMC medical education}, volume = {24}, number = {1}, pages = {1026}, pmid = {39300421}, issn = {1472-6920}, mesh = {Humans ; *Self Efficacy ; *Students, Medical/psychology ; Prospective Studies ; *Clinical Competence ; Male ; Female ; Cardiopulmonary Resuscitation/education ; Simulation Training ; Adult ; Emergency Medicine/education ; High Fidelity Simulation Training ; Young Adult ; Focus Groups ; Education, Medical, Undergraduate/methods ; Empowerment ; }, abstract = {BACKGROUND: High-fidelity simulations play a crucial role in preparing for high-mortality events like cardiopulmonary arrest, emphasizing the need for rapid and accurate intervention. Proficiency in cardiopulmonary resuscitation(CPR) requires a strong self-efficacy(SE); training for both is crucial. This study assesses the impact of Advanced Life Support(ALS) simulation on SE changes in final-year medical students.

METHODS: This mixed-methods prospective simulation study involved medical students in emergency medicine internships, examining self-efficacy perceptions regarding ALS technical skills(ALS-SEP). A comparison was made between students who underwent scenario-based ALS simulation training and those who did not. Competencies in chest compression skills were assessed, and the concordance between ALS-SEP scores and observed CPR performances were evaluated. Focus group interviews were conducted and analyzed using content analysis techniques.

RESULTS: The study involved 80 students, with 53 in the experimental group(EG) and 27 in the control group(CG). The EG, underwent simulation training, showed a significantly higher ALS-SEP change than the CG(p < 0.05). However, there was low concordance between pre-simulation SEP and actual performance. Compression skills success rates were inadequate. Qualitative analysis revealed main themes as"learning"(32.6%), "self-efficacy"(29%), "simulation method"(21.3%), and "development"(16.5%).

DISCUSSION: Post-simulation, students reported improved SEP and increased readiness for future interventions. The findings and qualitative statements support the effectiveness of simulation practices in bridging the gap between SEP and performance. Utilizing simulation-based ALS training enhances learners' belief in their capabilities, raises awareness of their competencies, and encourages reflective thinking. Given the importance of high SEP for ALS, simulation trainings correlating self-efficacy perception and performance may significantly reduce potential medical errors stemming from a disparity between perceived capability and actual performance.}, } @article {pmid39300071, year = {2024}, author = {Castelli, S and Desideri, E and Laureti, L and Felice, F and De Cristofaro, A and Scaricamazza, S and Lazzarino, G and Ciriolo, MR and Ciccarone, F}, title = {N-acetylaspartate promotes glycolytic-to-oxidative fiber-type switch and resistance to atrophic stimuli in myotubes.}, journal = {Cell death & disease}, volume = {15}, number = {9}, pages = {686}, pmid = {39300071}, issn = {2041-4889}, support = {GR-2019-1236998//Ministero della Salute (Ministry of Health, Italy)/ ; MNESYS PNRR - MUR PE00000006//Ministero della Salute (Ministry of Health, Italy)/ ; }, mesh = {Animals ; *Glycolysis/drug effects ; *Muscle Fibers, Skeletal/metabolism/drug effects ; Mice ; *Aspartic Acid/metabolism/analogs & derivatives ; Amyotrophic Lateral Sclerosis/metabolism/pathology/genetics ; Humans ; Oxidation-Reduction ; Cell Line ; Mice, Transgenic ; }, abstract = {N-acetylaspartate (NAA) is a neuronal metabolite that can be extruded in extracellular fluids and whose blood concentration increases in several neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS). Aspartoacylase (ASPA) is the enzyme responsible for NAA breakdown. It is abundantly expressed in skeletal muscle and most other human tissues, but the role of NAA catabolism in the periphery is largely neglected. Here we demonstrate that NAA treatment of differentiated C2C12 muscle cells increases lipid turnover, mitochondrial biogenesis and oxidative metabolism at the expense of glycolysis. These effects were ascribed to NAA catabolism, as CRISPR/Cas9 ASPA KO cells are insensitive to NAA administration. Moreover, the metabolic switch induced by NAA was associated with an augmented resistance to atrophic stimuli. Consistently with in vitro results, SOD1-G93A ALS mice show an increase in ASPA levels in those muscles undergoing the glycolytic to oxidative switch during the disease course. The impact of NAA on the metabolism and resistance capability of myotubes supports a role for this metabolite in the phenotypical adaptations of skeletal muscle in neuromuscular disorders.}, } @article {pmid39299905, year = {2024}, author = {Hetz, C and Thielen, P and Matus, S and Nassif, M and Court, F and Kiffin, R and Martinez, G and Cuervo, AM and Brown, RH and Glimcher, LH}, title = {Corrigendum: XBP-1 deficiency in the nervous system protects against amyotrophic lateral sclerosis by increasing autophagy.}, journal = {Genes & development}, volume = {38}, number = {15-16}, pages = {785}, doi = {10.1101/gad.352249.124}, pmid = {39299905}, issn = {1549-5477}, } @article {pmid39299508, year = {2024}, author = {Shetty, P and Ren, Y and Dillon, D and Mcleod, A and Nishijima, D and Taylor, SL and , }, title = {Derivation of a clinical decision rule for termination of resuscitation in non-traumatic pediatric out-of-hospital cardiac arrest.}, journal = {Resuscitation}, volume = {204}, number = {}, pages = {110400}, pmid = {39299508}, issn = {1873-1570}, support = {K38 HL165363/HL/NHLBI NIH HHS/United States ; }, mesh = {Humans ; *Out-of-Hospital Cardiac Arrest/therapy/mortality ; Male ; Female ; Retrospective Studies ; Child ; *Clinical Decision Rules ; *Cardiopulmonary Resuscitation/methods ; Child, Preschool ; Emergency Medical Services/methods ; Medical Futility ; Adolescent ; Infant ; Resuscitation Orders ; Withholding Treatment/standards ; }, abstract = {AIM: Prehospital termination of resuscitation (ToR) rules are used to predict medical futility in adult out-of-hospital cardiac arrest (OHCA), however, the available evidence for pediatric patients is limited. The primary aim of this study is to derive a Pediatric Termination of Resuscitation (PToR) prediction rule for use in pediatric non-traumatic OHCA patients.

METHODS: We analyzed a retrospective cohort of pediatric OHCA patients within the CARES database over a 10-year period (2013-2022). We split the dataset into training and test datasets and fit logistic regressions with Least Absolute Shrinkage and Selection Operator (LASSO) to select predictor variables and estimate predictive test characteristics for the primary outcome of death and a secondary composite outcome of death or survival to hospital discharge with unfavorable neurologic status.

RESULTS: We analyzed a sample of 21,240 children where 2,326 (11.0%) survived to hospital discharge, and 1,894 (8.9%) survived to hospital discharge with favorable neurologic status. We derived a PToR rule for death demonstrating a specificity of 99.1% and a positive predictive value (PPV) of 99.8% and a PToR rule for death or survival with poor neurologic status with a specificity of 99.7% and PPV of 99.9% within the test dataset.

CONCLUSION: We derived a clinical prediction rule with high specificity and positive predictive value in prehospital settings utilizing Advanced Life Support (ALS) providers which may inform termination of resuscitation considerations in pediatric patients. Further prospective and validation studies will be necessary to define the appropriateness and applicability of these PToR criteria for routine use.}, } @article {pmid39299489, year = {2024}, author = {Le, NT and Chu, N and Joshi, G and Higgins, NR and Nebie, O and Adelakun, N and Butts, M and Monteiro, MJ}, title = {Prion protein pathology in Ubiquilin 2 models of ALS.}, journal = {Neurobiology of disease}, volume = {201}, number = {}, pages = {106674}, pmid = {39299489}, issn = {1095-953X}, support = {K22 CA241105/CA/NCI NIH HHS/United States ; R01 NS098243/NS/NINDS NIH HHS/United States ; R35 GM151124/GM/NIGMS NIH HHS/United States ; RF1 NS098243/NS/NINDS NIH HHS/United States ; }, mesh = {*Amyotrophic Lateral Sclerosis/metabolism/genetics/pathology ; Animals ; Humans ; *Autophagy-Related Proteins/metabolism/genetics ; Mice ; *Adaptor Proteins, Signal Transducing/metabolism/genetics ; Mutation ; Disease Models, Animal ; Induced Pluripotent Stem Cells/metabolism/pathology ; Prion Proteins/metabolism/genetics ; Inclusion Bodies/metabolism/pathology ; Neurons/metabolism/pathology ; Mice, Transgenic ; }, abstract = {Mutations in UBQLN2 cause ALS and frontotemporal dementia (FTD). The pathological signature in UBQLN2 cases is deposition of highly unusual types of inclusions in the brain and spinal cord that stain positive for UBQLN2. However, what role these inclusions play in pathogenesis remains unclear. Here we show cellular prion protein (PrP[C]) is found in UBQLN2 inclusions in both mouse and human neuronal induced pluripotent (IPSC) models of UBQLN2 mutations, evidenced by the presence of aggregated forms of PrP[C] with UBQLN2 inclusions. Turnover studies indicated that the P497H UBQLN2 mutation slows PrP[C] protein degradation and leads to mislocalization of PrP[C] in the cytoplasm. Immunoprecipitation studies indicated UBQLN2 and PrP[C] bind together in a complex. The abnormalities in PrP[C] caused by UBQLN2 mutations may be relevant in disease pathogenesis.}, } @article {pmid39299156, year = {2024}, author = {Caswell, G and Wilson, E}, title = {The impact of home mechanical ventilation on the time and manner of death for those with Motor neurone disease (MND): A qualitative study of bereaved family members.}, journal = {Social science & medicine (1982)}, volume = {360}, number = {}, pages = {117345}, doi = {10.1016/j.socscimed.2024.117345}, pmid = {39299156}, issn = {1873-5347}, mesh = {Humans ; *Motor Neuron Disease/psychology/complications ; *Qualitative Research ; Male ; Female ; *Respiration, Artificial/psychology ; Middle Aged ; *Family/psychology ; United Kingdom ; Aged ; *Bereavement ; Attitude to Death ; Adult ; Terminal Care/psychology/methods ; Home Care Services ; Time Factors ; Aged, 80 and over ; }, abstract = {Motor neurone disease (MND) is a progressive neurodegenerative disorder which is ultimately terminal. It causes muscle weakness which can lead to the need for assistance in breathing, for some with the disease. This paper draws on qualitative research using semi-structured interviews with 32 people bereaved by the death of a family member with MND who was dependent on home mechanical ventilation, from across the United Kingdom. Interviews explored how the end-of-life of a person who had used non-invasive ventilation to assist their breathing was experienced by participants, who had cared about, and for them. Four themes are used to examine the impact of dependent ventilation technology on the experience of dying on the part of bereaved family members. Themes are: accompanied dying, planned withdrawal of ventilation, blurred time of death, time post-death. The perception and experience of time was a key component across all four themes. Ventilator technology played a critical role in sustaining life, but it could also contribute to a complex dynamic where the realities of death were mediated or obscured. This raises ethical, emotional, and existential considerations, both for the individuals receiving ventilator support and their families, as well as for healthcare professionals involved in end-of-life care.}, } @article {pmid39299050, year = {2024}, author = {Eshak, D and Arumugam, M}, title = {Unveiling therapeutic biomarkers and druggable targets in ALS: An integrative microarray analysis, molecular docking, and structural dynamic studies.}, journal = {Computational biology and chemistry}, volume = {113}, number = {}, pages = {108211}, doi = {10.1016/j.compbiolchem.2024.108211}, pmid = {39299050}, issn = {1476-928X}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy/metabolism ; *Molecular Docking Simulation ; *Biomarkers/metabolism/analysis/blood ; Microarray Analysis ; Molecular Dynamics Simulation ; }, abstract = {Amyotrophic lateral sclerosis (ALS), commonly known as Lou Gehrig's disease, is a debilitating neurodegenerative disorder characterized by the progressive degeneration of nerve cells in the brain and spinal cord. Despite extensive research, its precise etiology remains elusive, and early diagnosis is challenging due to the absence of specific tests. This study aimed to identify potential blood-based biomarkers for early ALS detection and monitoring using datasets from whole blood samples (GSE112680) and oligodendrocytes, astrocytes, and fibroblasts (GSE87385) obtained from the NCBI-GEO repository. Through bioinformatics analysis, including protein-protein interactions and molecular pathway analyses, we identified differentially expressed genes (DEGs) associated with ALS. Notably, ALS2, ADH7, ALDH8A1, ALDH3B1, ABHD2, ABHD17B, ABHD12, ABHD13, PGAM2, AURKB, ANAPC11, VAPA, UNC45B, and TNNT2 emerged as top-ranked DEGs, implicated in drug metabolism, protein depalmytilation, and the AKT/mTOR signaling pathways. Among these, AurKB established as a potential therapeutic biomarker with relevance to various neurological conditions. Consequently, AurKB was selected for identifying potential therapeutic molecules and utilized for in silico structural characterization studies. Exploration of the IMPATT database led to the discovery of a lead compound similar to Fostamatinib, currently used for AurKB. Initial molecular docking and MMGBSA-based binding energy analysis were followed by molecular dynamics simulation (MDS) and free energy landscape (FEL) analysis to validate the ligand's binding efficacy and understand dynamic processes within the biological system. The identified potential biomarkers and lead molecule provide novel insights into the correlation between blood cell transcripts and ALS pathology, paving the way for blood-based diagnostic tools for early ALS detection and ongoing disease monitoring.}, } @article {pmid39297270, year = {2024}, author = {Doğan, V and Şenormanci, Ö}, title = {Validity and Reliability of the Affective Lability Scale-18 (ALS-18) Turkish Form in the Non-Clinical Group.}, journal = {Turk psikiyatri dergisi = Turkish journal of psychiatry}, volume = {36}, number = {}, pages = {164-172}, pmid = {39297270}, issn = {2651-3463}, abstract = {OBJECTIVE: Affective lability, which is an important aspect of mood dysregulation, is seen in many psychiatric conditions. The aim of this study is to examine the psychometric properties of the Affective Lability Scale-18 in the Turkish sample of the non-clinical group.

METHOD: A total of 615 individuals (312 females and 303 males) who did not have a past or current psychiatric disorder were included in the study. The participants were administered sociodemographic data form, Affective Lability Scale-18, Difficulties in Emotion Regulation Scale, and Beck Depression Inventory. The participants were divided into 4 groups; a pilot group, EFA (exploratory factor analysis) group, CFA (confirmatory factor analysis) group and test-retest group.

RESULTS: The factor analysis conducted for the construct validity of the scale, revealed similar results to that of the original scale. The Cronbach's alpha internal consistency coefficient was 0.92 for the EFA group and 0.92 for the CFA group. The test-retest reliability coefficient was 0.82. Difficulties in Emotion Regulation Scale (DERS) and Beck's Depression Inventory (BDI) were used tp measure validity. The correlation between the total scores of participants on the ALS-18 and their scores on the DERS and BDI was determined to be positive and moderate (r=0.38, r=41).

CONCLUSION: The Affective Lability Scale-18 in the Turkish sample, three sub-dimensions, anxiety/depression, depression/elevation, anger and the general factor all have sufficient internal consistency and it has been demonstrated that the scale can be applied in our country to evaluate the situations in which affect variability is evaluated.}, } @article {pmid39296960, year = {2024}, author = {Keilholz, AN and Pathak, I and Smith, CL and Osman, KL and Smith, L and Oti, G and Golzy, M and Ma, L and Lever, TE and Nichols, NL}, title = {Tongue exercise ameliorates structural and functional upper airway deficits in a rodent model of hypoglossal motor neuron loss.}, journal = {Frontiers in neurology}, volume = {15}, number = {}, pages = {1441529}, pmid = {39296960}, issn = {1664-2295}, support = {T32 OD011126/OD/NIH HHS/United States ; }, abstract = {INTRODUCTION: Tongue weakness and atrophy can lead to deficits in the vital functions of breathing and swallowing in patients with motor neuron diseases (MNDs; e.g., amyotrophic lateral sclerosis (ALS) and pseudobulbar palsy), often resulting in aspiration pneumonia, respiratory failure, and death. Available treatments for patients with MNDs are largely palliative; thus, there is a critical need for therapies targeting preservation of upper airway function and suggesting a role for tongue exercise in patients with MNDs. Here, we leveraged our inducible rodent model of hypoglossal (XII) motor neuron degeneration to investigate the effects of a strength endurance tongue exercise program on upper airway structure and function. Our model was created through intralingual injection of cholera toxin B conjugated to saporin (CTB-SAP) into the genioglossus muscle of the tongue to induce targeted death of XII motor neurons.

METHODS: Rats in this study were allocated to 4 experimental groups that received intralingual injection of either CTB-SAP or unconjugated CTB + SAP (i.e., control) +/- tongue exercise. Following tongue exercise exposure, we evaluated the effect on respiratory function (via plethysmography), macrostructure [via magnetic resonance imaging (MRI) of the upper airway and tongue], and ultrafine structure [via ex vivo magnetic resonance spectroscopy (MRS) of the tongue] with a focus on lipid profiles.

RESULTS: Results showed that sham exercise-treated CTB-SAP rats have evidence of upper airway restriction (i.e., reduced airflow) and structural changes present in the upper airway (i.e., airway compression) when compared to CTB-SAP + exercise rats and control rats +/- tongue exercise, which was ameliorated with tongue exercise. Additionally, CTB-SAP + sham exercise rats have evidence of increased lipid expression in the tongue consistent with previously observed tongue hypertrophy when compared to CTB-SAP + exercise rats or control rats +/- tongue exercise.

CONCLUSION: These findings provide further evidence that a strength endurance tongue exercise program may be a viable therapeutic treatment option in patients with XII motor neuron degeneration in MNDs such as ALS. Future directions will focus on investigating the underlying mechanism responsible for tongue exercise-induced plasticity in the hypoglossal-tongue axis, particularly inflammatory associated factors such as BDNF.}, } @article {pmid39296911, year = {2024}, author = {Odat, RM and Alomari, O and Elgenidy, A}, title = {Evaluation of the gold cost criteria as a diagnostic criteria of amyotrophic lateral sclerosis.}, journal = {eNeurologicalSci}, volume = {37}, number = {}, pages = {100524}, pmid = {39296911}, issn = {2405-6502}, } @article {pmid39295200, year = {2025}, author = {Zhang, Z and He, X and Wang, J and Cui, J and Shi, B}, title = {The correlation between social support, coping style, advance care planning readiness, and quality of life in patients with amyotrophic lateral sclerosis: a cross-sectional study.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {26}, number = {1-2}, pages = {40-47}, doi = {10.1080/21678421.2024.2400520}, pmid = {39295200}, issn = {2167-9223}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/psychology/therapy ; Male ; Female ; Cross-Sectional Studies ; *Quality of Life/psychology ; *Social Support ; Middle Aged ; *Advance Care Planning ; *Adaptation, Psychological/physiology ; Aged ; Adult ; China ; Surveys and Questionnaires ; }, abstract = {OBJECTIVE: The primary goal for clinical healthcare professionals is to enhance the quality of life (QOL) of patients with amyotrophic lateral sclerosis (ALS). This study aimed to explore the correlation between social support, coping style, advance care planning (ACP) readiness, and QOL in patients with ALS. We also sought to analyze the mediating effect of coping style and ACP readiness between social support and QOL, and to provide insights for developing targeted interventions to improve patients' QOL.

METHODS: A cross-sectional design was used, with participants recruited through convenience sampling in Tianjin, China. Statistical analysis included the t-test, analysis of variance, correlation analysis, and mediating effect analysis.

RESULTS: The study included 215 participants. The QOL of patients with ALS was at a medium level, with significant correlations between social support, coping style, ACP readiness, and QOL (all p < 0.01). The direct effect of social support on QOL was 0.403 (p = 0.018), accounting for 41.85% of the total effect. The total indirect effect of social support on QOL through coping style and ACP readiness was 0.560 (p < 0.001), accounting for 58.15% of the total effect. The chain mediating effect involving facing, avoiding, and ACP readiness accounted for 16.72%.

CONCLUSION: Social support directly influenced QOL and had an indirect impact through coping style and ACP readiness. Healthcare professionals can improve the QOL of patients with ALS by enhancing social support, disease-coping ability, and ACP readiness in clinical practice.}, } @article {pmid39295118, year = {2024}, author = {Berry, JD and Paganoni, S and Harms, MB and Shneider, N and Andrews, J and Miller, TM and Babu, S and Sherman, AV and Harris, BT and Provenzano, FA and Phatnani, HP and Shefner, J and Garret, MA and Ladha, SS and Tsou, AY and Mohan, P and Igne, C and , and Bowser, R}, title = {Access for ALL in ALS: A large-scale, inclusive, collaborative consortium to unlock the molecular and genetic mechanisms of amyotrophic lateral sclerosis.}, journal = {Muscle & nerve}, volume = {70}, number = {6}, pages = {1140-1150}, pmid = {39295118}, issn = {1097-4598}, support = {OT2 NS136938/NS/NINDS NIH HHS/United States ; OT2 NS136939/NS/NINDS NIH HHS/United States ; 1OT2NS136939-01//National Institute of Neurological Disorders and Stroke, NIH/ ; 1OT2NS136938-01//National Institute of Neurological Disorders and Stroke, NIH/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/genetics ; Humans ; United States ; Biomedical Research ; National Institutes of Health (U.S.) ; }, abstract = {Recent progress in therapeutics for amyotrophic lateral sclerosis (ALS) has spurred development and imbued the field of ALS with hope for more breakthroughs, yet substantial scientific gaps persist. This unmet need remains a stark reminder that innovative paradigms are needed to invigorate ALS research. To move toward more informative, targeted, and personalized drug development, the National Institutes of Health (NIH) established a national ALS clinical research consortium called Access for ALL in ALS (ALL ALS). This new consortium is a multi-institutional effort that aims to organize the ALS clinical research landscape in the United States. ALL ALS is operating in partnership with several stakeholders to operationalize the recommendations of the Accelerating Access to Critical Therapies for ALS Act (ACT for ALS) Public Private Partnership. ALL ALS will provide a large-scale, centralized, and readily accessible infrastructure for the collection and storage of a wide range of data from people living with ALS (symptomatic cohort) or who may be at risk of developing ALS (asymptomatic ALS gene carriers). Importantly, ALL ALS is designed to encourage community engagement, equity, and inclusion. The consortium is prioritizing the enrollment of geographically, ethnoculturally, and socioeconomically diverse participants. Collected data include longitudinal clinical data and biofluids, genomic, and digital biomarkers that will be harmonized and linked to the central Accelerating Medicines Partnership for ALS (AMP ALS) portal for sharing with the research community. The aim of ALL ALS is to deliver a comprehensive, inclusive, open-science dataset to help researchers answer important scientific questions of clinical relevance in ALS.}, } @article {pmid39294194, year = {2024}, author = {Luthi-Carter, R and Cappelli, S and Le Roux-Bourdieu, M and Tentillier, N and Quinn, JP and Petrozziello, T and Gopalakrishnan, L and Sethi, P and Choudhary, H and Bartolini, G and Gebara, E and Stuani, C and Font, L and An, J and Ortega, V and Sage, J and Kosa, E and Trombetta, BA and Simeone, R and Seredenina, T and Afroz, T and Berry, JD and Arnold, SE and Carlyle, BC and Adolfsson, O and Sadri-Vakili, G and Buratti, E and Bowser, R and Agbas, A}, title = {Location and function of TDP-43 in platelets, alterations in neurodegenerative diseases and arising considerations for current plasma biobank protocols.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {21837}, pmid = {39294194}, issn = {2045-2322}, support = {P30 AG062421/AG/NIA NIH HHS/United States ; Industry-Led Consortium Project Grant//Target ALS Foundation/ ; BB-2022-C5//Target ALS Foundation/ ; }, mesh = {Humans ; *Blood Platelets/metabolism ; *DNA-Binding Proteins/metabolism ; *Neurodegenerative Diseases/blood/metabolism ; *Biological Specimen Banks ; Amyotrophic Lateral Sclerosis/blood/metabolism/pathology ; Biomarkers/blood ; Cytosol/metabolism ; }, abstract = {The TAR DNA Binding Protein 43 (TDP-43) has been implicated in the pathogenesis of human neurodegenerative diseases and exhibits hallmark neuropathology in amyotrophic lateral sclerosis (ALS). Here, we explore its tractability as a plasma biomarker of disease and describe its localization and possible functions in the cytosol of platelets. Novel TDP-43 immunoassays were developed on three different technical platforms and qualified for specificity, signal-to-noise ratio, detection range, variation, spike recovery and dilution linearity in human plasma samples. Surprisingly, implementation of these assays demonstrated that biobank-archived plasma samples yielded considerable heterogeneity in TDP-43 levels. Importantly, subsequent investigation attributed these differences to variable platelet recovery. Fractionations of fresh blood revealed that ≥ 95% of the TDP-43 in platelet-containing plasma was compartmentalized within the platelet cytosol. We reasoned that this highly concentrated source of TDP-43 comprised an interesting substrate for biochemical analyses. Additional characterization of platelets revealed the presence of the disease-associated phosphoserine 409/410 TDP-43 proteoform and many neuron- and astrocyte-expressed TDP-43 mRNA targets. Considering these striking similarities, we propose that TDP-43 may serve analogous functional roles in platelets and synapses, and that the study of platelet TDP-43 might provide a window into disease-related TDP-43 dyshomeostasis in the central nervous system.}, } @article {pmid39293800, year = {2024}, author = {Gao, J and Chai, N and Wang, T and Han, Z and Chen, J and Lin, G and Wu, Y and Bi, L}, title = {A new technique of percutaneous minimally invasive surgery assisted by magnetic resonance neurography.}, journal = {Bone & joint open}, volume = {5}, number = {9}, pages = {776-784}, pmid = {39293800}, issn = {2633-1462}, abstract = {AIMS: In order to release the contracture band completely without damaging normal tissues (such as the sciatic nerve) in the surgical treatment of gluteal muscle contracture (GMC), we tried to display the relationship between normal tissue and contracture bands by magnetic resonance neurography (MRN) images, and to predesign a minimally invasive surgery based on the MRN images in advance.

METHODS: A total of 30 patients (60 hips) were included in this study. MRN scans of the pelvis were performed before surgery. The contracture band shape and external rotation angle (ERA) of the proximal femur were also analyzed. Then, the minimally invasive GMC releasing surgery was performed based on the images and measurements, and during the operation, incision lengths, surgery duration, intraoperative bleeding, and complications were recorded; the time of the first postoperative off-bed activity was also recorded. Furthermore, the patients' clinical functions were evaluated by means of Hip Outcome Score (HOS) and Ye et al's objective assessments, respectively.

RESULTS: The contracture bands exhibited three typical types of shape - feather-like, striped, and mixed shapes - in MR images. Guided by MRN images, we designed minimally invasive approaches directed to each hip. These approaches resulted in a shortened incision length in each hip (0.3 cm (SD 0.1)), shorter surgery duration (25.3 minutes (SD 5.8)), less intraoperative bleeding (8.0 ml (SD 3.6)), and shorter time between the end of the operation and the patient's first off-bed activity (17.2 hours (SD 2.0)) in each patient. Meanwhile, no serious postoperative complications occurred in all patients. The mean HOS-Sports subscale of patients increased from 71.0 (SD 5.3) to 94.83 (SD 4.24) at six months postoperatively (p < 0.001). The follow-up outcomes from all patients were "good" and "excellent", based on objective assessments.

CONCLUSION: Preoperative MRN analysis can be used to facilitate the determination of the relationship between contracture band and normal tissues. The minimally invasive surgical design via MRN can avoid nerve damage and improve the release effect.}, } @article {pmid39293008, year = {2024}, author = {Ramirez, V and Kittrell, P and Jackson, C and Clegg, A and Allegretti, A}, title = {Sexual Intimacy in Persons with Amyotrophic Lateral Sclerosis and their Partners: A Pilot Study.}, journal = {Journal of allied health}, volume = {53}, number = {3}, pages = {212-217}, pmid = {39293008}, issn = {1945-404X}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/psychology ; Pilot Projects ; Male ; Female ; Middle Aged ; *Sexual Partners/psychology ; Aged ; Sexual Behavior ; Adult ; Quality of Life ; }, abstract = {OBJECTIVE: The objective of this study was to describe concerns experienced among persons with amyotrophic lateral sclerosis (PALS) and their partners regarding sexual intimacy, as well as preferences regarding discussion of the topic with healthcare providers.

METHODS: A total of 27 survey responses including 13 PALS and 14 partners were received. Surveys included both quantitative and qualitative data addressing the importance of sexual intimacy to quality of life, assistance required to participate in sexual intimacy, concerns for safety, and preferred timing and method of discussing/receiving information from healthcare professionals.

RESULTS: 100% of respondents stated they had never been asked about sexual intimacy by any healthcare provider. 92% of participants agreed ALS had affected their ability to express sexual intimacy. Participants discussed loss of intimacy as due to muscle weakness, respiratory concerns, and role change among other contributors to the overall experienced change in expression of sexual intimacy. With regards to their preferred method of receiving/discussing information on the effect of ALS on sexual intimacy, 48% of participants preferred use of an online video series, 44% chose a pamphlet, 24% chose a one-on-one discussion with a healthcare provider, and 12% chose a private conversation with their partner and healthcare provider.

CONCLUSIONS: The findings greatly illustrate the difficulties and concerns experienced with sexual intimacy among PALS and their partners as well as the preferred methods for receiving information on the topic.}, } @article {pmid39292705, year = {2024}, author = {Minnella, A and McCusker, KP and Amagata, A and Trias, B and Weetall, M and Latham, JC and O'Neill, S and Wyse, RK and Klein, MB and Trimmer, JK}, title = {Targeting ferroptosis with the lipoxygenase inhibitor PTC-041 as a therapeutic strategy for the treatment of Parkinson's disease.}, journal = {PloS one}, volume = {19}, number = {9}, pages = {e0309893}, pmid = {39292705}, issn = {1932-6203}, mesh = {Animals ; *Ferroptosis/drug effects ; *Lipoxygenase Inhibitors/pharmacology/therapeutic use ; Humans ; *Parkinson Disease/drug therapy/metabolism/pathology ; Rats ; Mice ; alpha-Synuclein/metabolism ; Lipid Peroxidation/drug effects ; Neurons/drug effects/metabolism/pathology ; Fibroblasts/drug effects/metabolism ; Arachidonate 15-Lipoxygenase/metabolism ; Cells, Cultured ; Male ; }, abstract = {Parkinson's disease is the second most common neurodegenerative disorder, affecting nearly 10 million people worldwide. Ferroptosis, a recently identified form of regulated cell death characterized by 15-lipoxygenase-mediated hydroperoxidation of membrane lipids, has been implicated in neurodegenerative disorders including amyotrophic lateral sclerosis and Parkinson's disease. Pharmacological inhibition of 15 -lipoxygenase to prevent iron- and lipid peroxidation-associated ferroptotic cell death is a rational strategy for the treatment of Parkinson's disease. We report here the characterization of PTC-041 as an anti-ferroptotic reductive lipoxygenase inhibitor developed for the treatment of Parkinson's disease. In these studies, PTC-041 potently protects primary human Parkinson's disease patient-derived fibroblasts from lipid peroxidation and subsequent ferroptotic cell death and prevents ferroptosis-related neuronal loss and astrogliosis in primary rat neuronal cultures. Additionally, PTC-041 prevents ferroptotic-mediated α-synuclein protein aggregation and nitrosylation in vitro, suggesting a potential role for anti-ferroptotic lipoxygenase inhibitors in mitigating pathogenic aspects of synucleinopathies such as Parkinson's disease. We further found that PTC-041 protects against synucleinopathy in vivo, demonstrating that PTC-041 treatment of Line 61 transgenic mice protects against α-synuclein aggregation and phosphorylation as well as prevents associated neuronal and non-neuronal cell death. Finally, we show that. PTC-041 protects against 6-hydroxydopamine-induced motor deficits in a hemiparkinsonian rat model, further validating the potential therapeutic benefits of lipoxygenase inhibitors in the treatment of Parkinson's disease.}, } @article {pmid39292682, year = {2024}, author = {Tang, X and Li, Q and Huang, G and Pei, X and Chen, Z and Huang, Y and Zhao, S and Guo, T and Liu, Z}, title = {Immediate efficacy of auricular acupuncture combined with active exercise in the treatment of acute lumbar sprains in 10 minutes: Protocol of a randomized controlled trial.}, journal = {PloS one}, volume = {19}, number = {9}, pages = {e0308801}, pmid = {39292682}, issn = {1932-6203}, mesh = {Adolescent ; Adult ; Female ; Humans ; Male ; Middle Aged ; Young Adult ; *Acupuncture, Ear/methods ; Combined Modality Therapy ; *Exercise Therapy/methods ; Low Back Pain/therapy ; Lumbar Vertebrae/physiopathology ; Lumbosacral Region ; Pain Measurement ; Prospective Studies ; Range of Motion, Articular ; Sprains and Strains/therapy ; Treatment Outcome ; Randomized Controlled Trials as Topic ; }, abstract = {BACKGROUND: Acute lumbar sprain (ALS) is common musculoskeletal disorder characterized by severe low back pain and activity limitation, which significantly impacts the patient's work and life. Immediate relief of pain and restoration of mobility in a short period of time are the main needs of patients when they visit the clinic. This study aims to evaluate the immediate efficacy of this combined treatment for ALS within 10 minutes.

METHODS: This is a single-center, prospective, randomized clinical trial. 128 eligible patients with ALS will be randomly allocated in a 1:1 ratio to either the auricular acupuncture (AA) group or the sham auricular acupuncture (SAA) group. All patients will receive a single 10-minute treatment. The primary outcome will be the change in pain intensity after 10 minutes of treatment. The secondary outcomes include changes in pain intensity at other time points (2, 5 minutes), changes in lumbar range of motion (ROM) at different time points, blinded assessment, treatment effect expectancy scale evaluation, and treatment satisfaction scale evaluation. All participants will be included in the analysis according to the intention-to-treat principle.

DISCUSSION: This is the first randomized controlled trial to assess the immediate efficacy of AA combined with active exercise for ALS. The findings of this study are expected to provide a simple and rapid treatment for ALS in clinical.

TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2400083740. Registered 30 April 2024.}, } @article {pmid39292611, year = {2024}, author = {Xu, Z and Tang, J and Gong, Y and Zhang, J and Zou, Y}, title = {Atomistic Insights into the Stabilization of TDP-43 Protofibrils by ATP.}, journal = {Journal of chemical information and modeling}, volume = {64}, number = {19}, pages = {7639-7649}, doi = {10.1021/acs.jcim.4c01140}, pmid = {39292611}, issn = {1549-960X}, mesh = {*Adenosine Triphosphate/metabolism ; *Molecular Dynamics Simulation ; *DNA-Binding Proteins/chemistry/metabolism ; Humans ; Protein Stability ; Hydrogen Bonding ; }, abstract = {The aberrant accumulation of the transactive response deoxyribonucleic acid (DNA)-binding protein of 43 kDa (TDP-43) aggregates in the cytoplasm of motor neurons is the main pathological hallmark of amyotrophic lateral sclerosis (ALS). Previous experiments reported that adenosine triphosphate (ATP), the universal energy currency for all living cells, could induce aggregation and enhance the folding of TDP-43 fibrillar aggregates. However, the significance of ATP on TDP-43 fibrillation and the mechanism behind it remain elusive. In this work, we conducted multiple atomistic molecular dynamics (MD) simulations totaling 20 μs to search the critical nucleus size of TDP-43282-360 and investigate the impact of ATP molecules on preformed protofibrils. The results reveal that the trimer is the critical nucleus for TDP-43282-360 fibril formation and the tetramer is the minimal stable nucleus. When ATP molecules bind to the TDP-43282-360 trimer and tetramer, they can consolidate the TDP-43282-360 protofibrils by increasing the content of the β-sheet structure and promoting the formation of hydrogen bonds (H-bonds). Binding site analyses show that the N-terminus of TDP-43282-360 protofibrils is the main binding site of ATP, and R293 dominates the direct binding of ATP. Further analyses reveal that the π-π, cation-π, salt bridge, and H-bonding interactions together contribute to the binding of ATP to TDP-43282-360 protofibrils. This study decoded the detailed stabilization mechanism of protofibrillar TDP-43282-360 oligomers by ATP, and may provide new avenues for the development of drug design against ALS.}, } @article {pmid39292414, year = {2024}, author = {Ataman, R and Alhasani, R and Auneau-Enjalbert, L and Quigley, A and Michael, HU and Ahmed, S}, title = {The psychometric properties of the Quality of Life in Neurological Disorders (Neuro-QoL) measurement system in neurorehabilitation populations: a systematic review.}, journal = {Journal of patient-reported outcomes}, volume = {8}, number = {1}, pages = {106}, pmid = {39292414}, issn = {2509-8020}, support = {36053//Canadian Foundation of Innovation and the Ministry of Health of Quebec/ ; }, mesh = {Humans ; *Nervous System Diseases/rehabilitation/psychology/diagnosis ; *Neurological Rehabilitation/methods ; *Psychometrics/methods ; *Quality of Life/psychology ; Reproducibility of Results ; }, abstract = {OBJECTIVE: To systematically review the literature of existing evidence on the measurement properties of the Quality of Life in Neurological Disorders (Neuro-QoL) measurement system among neurorehabilitation populations.

DATA SOURCES: The Consensus-based Standards for the selection of health Measurement Instruments (COSMIN) guided this systematic review in which we searched nine electronic databases and registries, and hand-searched reference lists of included articles.

STUDY SELECTION: Two independent reviewers screened selected articles and extracted data from 28 included studies.

DATA EXTRACTION: COSMIN's approach guided extraction and synthesizing measurement properties evidence (insufficient, sufficient), and the modified GRADE approach guided synthesizing evidence quality (very-low, low, moderate, high) by diagnosis.

DATA SYNTHESIS: Neuro-QoL has sufficient measurement properties when used by individuals with Huntington's disease, Multiple Sclerosis, Parkinson's disease, stroke, lupus, cognitive decline, and amyotrophic lateral sclerosis. The strongest evidence is for the first four conditions, where test-retest reliability, construct validity, and responsiveness are nearly always sufficient (GRADE: moderate-high). Structural validity is assessed only in multiple sclerosis and stroke but is often insufficient (GRADE: moderate-high). Criterion validity is sufficient in some stroke and Huntington's disease domains (GRADE: high). Item response theory analyses were reported for some stroke domains only. There is limited, mixed evidence for responsiveness and measurement error (GRADE: moderate-high), and no cross-cultural validity evidence CONCLUSIONS: Neuro-QoL domains can describe and evaluate patients with Huntington's disease, multiple sclerosis, Parkinson's disease, and stroke, but predictive validity evidence would be beneficial. In the other conditions captured in this review, a limited number of Neuro-QoL domains have evidence for descriptive use only. For these conditions, further evidence of structural validity, measurement error, cross-cultural validity and predictive validity would enhance the use and interpretation of Neuro-QoL.}, } @article {pmid39292338, year = {2025}, author = {Zhang, H and Gao, C and Yang, D and Nie, L and He, K and Chen, C and Li, S and Huang, G and Zhou, L and Huang, X and Wu, D and Liu, J and Huang, Z and Wang, J and Li, W and Zhang, Z and Yang, X and Zou, L}, title = {Urolithin a Improves Motor Dysfunction Induced by Copper Exposure in SOD1[G93A] Transgenic Mice Via Activation of Mitophagy.}, journal = {Molecular neurobiology}, volume = {62}, number = {6}, pages = {6922-6937}, pmid = {39292338}, issn = {1559-1182}, mesh = {Animals ; Mice, Transgenic ; *Copper/toxicity ; *Mitophagy/drug effects ; *Coumarins/pharmacology/therapeutic use ; Amyotrophic Lateral Sclerosis/drug therapy/pathology/physiopathology ; Mice ; Motor Neurons/drug effects/metabolism/pathology ; *Superoxide Dismutase-1/genetics/metabolism ; Mitochondria/drug effects/metabolism ; Spinal Cord/pathology/drug effects/metabolism ; Male ; Astrocytes/drug effects/metabolism/pathology ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease pathologically characterized by selective degeneration of motor neurons resulting in a catastrophic loss of motor function. The present study aimed to investigate the effect of copper (Cu) exposure on progression of ALS and explore the therapeutic effect and mechanism of Urolithin A (UA) on ALS. 0.13 PPM copper chloride drinking water was administrated in SOD1[G93A] transgenic mice at 6 weeks, UA at a dosage of 50 mg/kg/day was given for 6 weeks after a 7-week Cu exposure. Motor ability was assessed before terminal anesthesia. Muscle atrophy and fibrosis, motor neurons, astrocytes and microglia in the spinal cord were evaluated by H&E, Masson, Sirius Red, Nissl and Immunohistochemistry Staining. Proteomics analysis, Western blotting and ELISA were conducted to detect protein expression. Mitochondrial adenosine triphosphate (ATP) and malondialdehyde (MDA) levels were measured using an assay kit. Cu-exposure worsened motor function, promoted muscle fibrosis, loss of motor neurons, and astrocyte and microglial activation. It also induced abnormal changes in mitochondria-related biological processes, leading to a significant reduction in ATP levels and an increase in MDA levels. Upregulation of P62 and downregulation of Parkin, PINK1, and LAMP1 were revealed in SOD1[G93A] mice with Cu exposure. Administration of UA activated mitophagy, modulated mitochondria dysfunction, reduced neuroinflammation, and improved gastrocnemius muscle atrophy and motor dysfunction in SOD1[G93A] mice with Cu exposure. Mitophagy plays critical role in ALS exacerbated by Cu exposure. UA administration may be a promising treatment strategy for ALS.}, } @article {pmid39291248, year = {2024}, author = {Senerchia, G and Dubbioso, R}, title = {Non-invasive brain stimulation therapy in amyotrophic lateral sclerosis: are we ready for clinical use?.}, journal = {The Lancet regional health. Europe}, volume = {45}, number = {}, pages = {101055}, pmid = {39291248}, issn = {2666-7762}, } @article {pmid39291166, year = {2024}, author = {Gianferrari, G and Cuoghi Costantini, R and Crippa, V and Carra, S and Bonetto, V and Pansarasa, O and Cereda, C and Zucchi, E and Martinelli, I and Simonini, C and Vicini, R and Fini, N and Trojsi, F and Passaniti, C and Ticozzi, N and Doretti, A and Diamanti, L and Fiamingo, G and Conte, A and Dalla Bella, E and D'Errico, E and Scarian, E and Pasetto, L and Antoniani, F and Galli, V and Casarotto, E and , and D'Amico, R and Poletti, A and Mandrioli, J}, title = {Colchicine treatment in amyotrophic lateral sclerosis: safety, biological and clinical effects in a randomized clinical trial.}, journal = {Brain communications}, volume = {6}, number = {5}, pages = {fcae304}, pmid = {39291166}, issn = {2632-1297}, abstract = {In preclinical studies, the anti-inflammatory drug colchicine, which has never been tested in amyotrophic lateral sclerosis, enhanced the expression of autophagy factors and inhibited accumulation of transactive response DNA-binding protein 43 kDa, a known histopathological marker of amyotrophic lateral sclerosis. This multicentre, randomized, double-blind trial enrolled patients with probable or definite amyotrophic lateral sclerosis who experienced symptom onset within the past 18 months. Patients were randomly assigned in a 1:1:1 ratio to receive colchicine at a dose of 0.005 mg/kg/day, 0.01 mg/kg/day or placebo for a treatment period of 30 weeks. The number of positive responders, defined as patients with a decrease lesser than 4 points in the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised total score during the 30-week treatment period, was the primary outcome. Disease progression, survival, safety and quality of life at the end of treatment were the secondary clinical outcomes. Secondary biological outcomes included changes from baseline to treatment end of stress granule and autophagy responses, transactive response DNA-binding protein 43 kDa, neurofilament accumulation and extracellular vesicle secretion, between the colchicine and placebo groups. Fifty-four patients were randomized to receive colchicine (n = 18 for each colchicine arm) or placebo (n = 18). The number of positive responders did not differ between the placebo and colchicine groups: 2 out of 18 patients (11.1%) in the placebo group, 5 out of 18 patients (27.8%) in the colchicine 0.005 mg/kg/day group (odds ratio = 3.1, 97.5% confidence interval 0.4-37.2, P = 0.22) and 1 out of 18 patients (5.6%) in the colchicine 0.01 mg/kg/day group (odds ratio = 0.5, 97.5% confidence interval 0.01-10.2, P = 0.55). During treatment, a slower Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised decline was detected in patients receiving colchicine 0.005 mg/kg/day (mean difference = 0.53, 97.5% confidence interval 0.07-0.99, P = 0.011). Eight patients experienced adverse events in placebo arm (44.4%), three in colchicine 0.005 mg/kg/day (16.7%) and seven in colchicine 0.01 mg/kg/day arm (35.9%). The differences in adverse events were not statistically significant. In conclusion, colchicine treatment was safe for amyotrophic lateral sclerosis patients. Further studies are required to better understand mechanisms of action and clinical effects of colchicine in this condition.}, } @article {pmid39290830, year = {2024}, author = {Noches, V and Campos-Melo, D and Droppelmann, CA and Strong, MJ}, title = {Epigenetics in the formation of pathological aggregates in amyotrophic lateral sclerosis.}, journal = {Frontiers in molecular neuroscience}, volume = {17}, number = {}, pages = {1417961}, pmid = {39290830}, issn = {1662-5099}, abstract = {The progressive degeneration of motor neurons in amyotrophic lateral sclerosis (ALS) is accompanied by the formation of a broad array of cytoplasmic and nuclear neuronal inclusions (protein aggregates) largely containing RNA-binding proteins such as TAR DNA-binding protein 43 (TDP-43) or fused in sarcoma/translocated in liposarcoma (FUS/TLS). This process is driven by a liquid-to-solid phase separation generally from proteins in membrane-less organelles giving rise to pathological biomolecular condensates. The formation of these protein aggregates suggests a fundamental alteration in the mRNA expression or the levels of the proteins involved. Considering the role of the epigenome in gene expression, alterations in DNA methylation, histone modifications, chromatin remodeling, non-coding RNAs, and RNA modifications become highly relevant to understanding how this pathological process takes effect. In this review, we explore the evidence that links epigenetic mechanisms with the formation of protein aggregates in ALS. We propose that a greater understanding of the role of the epigenome and how this inter-relates with the formation of pathological LLPS in ALS will provide an attractive therapeutic target.}, } @article {pmid39290715, year = {2024}, author = {Huang, L and Liu, M and Tang, J and Gong, Z and Li, Z and Yang, Y and Zhang, M}, title = {The role of ALDH2 rs671 polymorphism and C-reactive protein in the phenotypes of male ALS patients.}, journal = {Frontiers in neuroscience}, volume = {18}, number = {}, pages = {1397991}, pmid = {39290715}, issn = {1662-4548}, abstract = {BACKGROUND: The aldehyde dehydrogenase 2 (ALDH2) rs671 (A) allele has been implicated in neurodegeneration, potentially through oxidative and inflammatory pathways. The study aims to investigate the effects of the ALDH2 rs671 (A) allele and high sensitivity C-reactive protein (hs-CRP) on the clinical phenotypes of amyotrophic lateral sclerosis (ALS) in male and female patients.

METHODS: Clinical data and ALDH2 rs671 genotype of 143 ALS patients, including 85 males and 58 females, were collected from January 2018 to December 2022. All patients underwent assessment using the Chinese version of the Edinburgh Cognitive and Behavioral ALS Screen (ECAS). Complete blood count and metabolic profiles were measured. Clinical and laboratory parameters were compared between carriers and non-carriers of the rs671 (A) allele in males and females, respectively. The significant parameters and rs671 (A) Allele were included in multivariate linear regression models to identify potential contributors to motor and cognitive impairment. Mediation analysis was employed to evaluate any mediation effects.

RESULTS: Male patients carrying rs671 (A) allele exhibited higher levels of hs-CRP than non-carriers (1.70 mg/L vs. 0.50 mg/L, p = 0.006). The rs671 (A) allele was identified as an independent risk factor for faster disease progression only in male patients (β = 0.274, 95% CI = 0.048-0.499, p = 0.018). The effect of the rs671 (A) allele on the executive function in male patients was fully mediated by hs-CRP (Indirect effect = -1.790, 95% CI = -4.555--0.225). No effects of the rs671 (A) allele or hs-CRP were observed in female ALS patients. The effects of the ALDH2 rs671 (A) allele and the mediating role of hs-CRP in male patients remained significant in the sensitivity analyses.

CONCLUSION: The ALDH2 rs671 (A) allele contributed to faster disease progression and hs-CRP mediated cognitive impairment in male ALS patients.}, } @article {pmid39289761, year = {2024}, author = {van der Geest, AT and Jakobs, CE and Ljubikj, T and Huffels, CFM and Cañizares Luna, M and Vieira de Sá, R and Adolfs, Y and de Wit, M and Rutten, DH and Kaal, M and Zwartkruis, MM and Carcolé, M and Groen, EJN and Hol, EM and Basak, O and Isaacs, AM and Westeneng, HJ and van den Berg, LH and Veldink, JH and Schlegel, DK and Pasterkamp, RJ}, title = {Molecular pathology, developmental changes and synaptic dysfunction in (pre-) symptomatic human C9ORF72-ALS/FTD cerebral organoids.}, journal = {Acta neuropathologica communications}, volume = {12}, number = {1}, pages = {152}, pmid = {39289761}, issn = {2051-5960}, support = {TOTALS//Stichting ALS Nederland/ ; ALS-on-a-chip//Stichting ALS Nederland/ ; MUS-ALS//Stichting ALS Nederland/ ; ATAXALS//Stichting ALS Nederland/ ; GoALS//Stichting ALS Nederland/ ; INTEGRALS//E-Rare/ ; TRIAGE//JPND/ ; EScORIAL/ERC_/European Research Council/International ; }, mesh = {Humans ; *Organoids/pathology ; *Frontotemporal Dementia/genetics/pathology ; *Amyotrophic Lateral Sclerosis/genetics/pathology ; *C9orf72 Protein/genetics ; *Induced Pluripotent Stem Cells/pathology ; *Synapses/pathology/genetics ; Male ; Female ; Cerebral Cortex/pathology ; DNA Repeat Expansion/genetics ; }, abstract = {A hexanucleotide repeat expansion (HRE) in C9ORF72 is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Human brain imaging and experimental studies indicate early changes in brain structure and connectivity in C9-ALS/FTD, even before symptom onset. Because these early disease phenotypes remain incompletely understood, we generated iPSC-derived cerebral organoid models from C9-ALS/FTD patients, presymptomatic C9ORF72-HRE (C9-HRE) carriers, and controls. Our work revealed the presence of all three C9-HRE-related molecular pathologies and developmental stage-dependent size phenotypes in cerebral organoids from C9-ALS/FTD patients. In addition, single-cell RNA sequencing identified changes in cell type abundance and distribution in C9-ALS/FTD organoids, including a reduction in the number of deep layer cortical neurons and the distribution of neural progenitors. Further, molecular and cellular analyses and patch-clamp electrophysiology detected various changes in synapse structure and function. Intriguingly, organoids from all presymptomatic C9-HRE carriers displayed C9-HRE molecular pathology, whereas the extent to which more downstream cellular defects, as found in C9-ALS/FTD models, were detected varied for the different presymptomatic C9-HRE cases. Together, these results unveil early changes in 3D human brain tissue organization and synaptic connectivity in C9-ALS/FTD that likely constitute initial pathologies crucial for understanding disease onset and the design of therapeutic strategies.}, } @article {pmid39289471, year = {2024}, author = {Jawdat, O and Rucker, J and Nakano, T and Takeno, K and Statland, J and Pasnoor, M and Dimachkie, MM and Sabus, C and Badawi, Y and Hunt, SL and Tomioka, NH and Gunewardena, S and Bloomer, C and Wilkins, HM and Herbelin, L and Barohn, RJ and Nishimune, H}, title = {Resistance exercise in early-stage ALS patients, ALSFRS-R, Sickness Impact Profile ALS-19, and muscle transcriptome: a pilot study.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {21729}, pmid = {39289471}, issn = {2045-2322}, support = {P30 GM122731/GM/NIGMS NIH HHS/United States ; R01NS078214/NS/NINDS NIH HHS/United States ; P30 AG035982/AG/NIA NIH HHS/United States ; R01 NS078214/NS/NINDS NIH HHS/United States ; U54 HD090216/HD/NICHD NIH HHS/United States ; S10 OD021743/OD/NIH HHS/United States ; 19K24690//Japan Society for the Promotion of Science/ ; UL1 TR002366/TR/NCATS NIH HHS/United States ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/physiopathology ; Pilot Projects ; Male ; *Resistance Training ; Female ; Middle Aged ; *Transcriptome ; *Muscle Strength ; Aged ; Adult ; Quadriceps Muscle/metabolism/physiopathology ; Muscle, Skeletal/metabolism/physiopathology ; }, abstract = {Amyotrophic lateral sclerosis (ALS) patients lack effective treatments to maintain motor and neuromuscular function. This study aimed to evaluate the effect of a home-based exercise program on muscle strength, ALS scores, and transcriptome in ALS patients, Clinical Trials.gov #NCT03201991 (28/06/2017). An open-label, non-randomized pilot clinical trial was conducted in seven individuals with early-stage ALS. Participants were given 3 months of home-based resistance exercise focusing on the quadriceps muscles. The strength of exercised muscle was evaluated using bilateral quadriceps strength with manual muscle testing, handheld dynamometers, five times sit-to-stand, and Timed-Up-and-Go before and after the exercise program. In addition, changes in the Sickness Impact Profile ALS-19 (SIP/ALS-19) as the functional outcome measure and the transcriptome of exercised muscles were compared before and after the exercise. The primary outcome of muscle strength did not change significantly by the exercise program. The exercise program maintained the SIP/ALS-19 and the ALS Functional Rating Scale-Revised (ALSFRS-R). Transcriptome analysis revealed that exercise reverted the expression level of genes decreased in ALS, including parvalbumin. Three months of moderately intense strength and conditioning exercise maintained muscle strength of the exercised muscle and ALSFRS-R scores and had a positive effect on patients' muscle transcriptome.}, } @article {pmid39289025, year = {2024}, author = {Dunlop, CL and Kilpatrick, C and Jones, L and Bonet, M and Allegranzi, B and Brizuela, V and Graham, W and Thompson, A and Cheshire, J and Lissauer, D}, title = {Adapting the WHO hand hygiene 'reminders in the workplace' to improve acceptability for healthcare workers in maternity settings worldwide: a mixed methods study.}, journal = {BMJ open}, volume = {14}, number = {9}, pages = {e083132}, pmid = {39289025}, issn = {2044-6055}, support = {001/WHO_/World Health Organization/International ; }, mesh = {Humans ; *Hand Hygiene ; *Focus Groups ; Female ; *World Health Organization ; *Health Personnel/psychology ; Workplace ; Attitude of Health Personnel ; Reminder Systems ; Adult ; Male ; Cross Infection/prevention & control ; Surveys and Questionnaires ; Hospitals, Maternity ; Developing Countries ; Guideline Adherence ; Interviews as Topic ; }, abstract = {INTRODUCTION: Hand hygiene is key in preventing healthcare-associated infections, but it is challenging in maternity settings due to high patient turnover, frequent emergencies and volume of aseptic procedures. We sought to investigate if adaptions to the WHO hand hygiene reminders could improve their acceptability in maternity settings globally, and use these findings to develop new reminders specific to maternity settings.

METHODS: Informed by Sekhon et al's acceptability framework, we conducted an online survey, semi-structured interviews and a focus group examining the three WHO central hand hygiene reminders ('your five moments of hand hygiene', 'how to hand wash' and 'how to hand rub') and their acceptability in maternity settings. A convergent mixed-methods study design was followed. Findings were examined overall and by country income status. A WHO expert working group tested the integrated findings, further refined results and developed recommendations to improve acceptability for use in the global maternity community. Findings were used to inform the development of two novel and acceptable hand hygiene reminders for use in high-income country (HIC) and low- and middle-income country (LMIC) maternity settings.

RESULTS: Participation in the survey (n=342), semi-structured interviews (n=12) and focus group (n=7) spanned 51 countries (14 HICs and 37 LMICs). The highest scoring acceptability constructs were clarity of the intervention (intervention coherence), confidence in performance (self-efficacy), and alignment with personal values (ethicality). The lowest performing were perceived difficulty (burden) and how the intervention made the participant feel (affective attitude). Overfamiliarity reduced acceptability in HICs (perceived effectiveness). In LMICs, resource availability was a barrier to implementation (opportunity cost). Two new reminders were developed based on the findings, using inclusive female images, and clinical examples from maternity settings.

CONCLUSION: Following methodologically robust adaptation, two novel and inclusive maternity-specific hand hygiene reminders have been developed for use in both HIC and LMICs.}, } @article {pmid39288267, year = {2024}, author = {Liu, H and Zhao, XF and Lu, YN and Hayes, LR and Wang, J}, title = {CRISPR/Cas13d targeting suppresses repeat-associated non-AUG translation of C9orf72 hexanucleotide repeat RNA.}, journal = {The Journal of clinical investigation}, volume = {134}, number = {21}, pages = {}, pmid = {39288267}, issn = {1558-8238}, support = {R01 NS123538/NS/NINDS NIH HHS/United States ; R01 NS128494/NS/NINDS NIH HHS/United States ; R01 NS074324/NS/NINDS NIH HHS/United States ; R01 NS110098/NS/NINDS NIH HHS/United States ; R01 NS089616/NS/NINDS NIH HHS/United States ; }, mesh = {*C9orf72 Protein/genetics/metabolism ; Humans ; Animals ; *Amyotrophic Lateral Sclerosis/genetics/pathology/therapy/metabolism ; *CRISPR-Cas Systems ; Mice ; *Frontotemporal Dementia/genetics/pathology/metabolism ; *DNA Repeat Expansion/genetics ; *Mice, Transgenic ; Protein Biosynthesis ; Induced Pluripotent Stem Cells/metabolism ; RNA/genetics/metabolism ; Motor Neurons/metabolism/pathology ; }, abstract = {A hexanucleotide GGGGCC repeat expansion in the non-coding region of the C9orf72 gene is the most common genetic mutation identified in patients with amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The resulting repeat RNA and dipeptide repeat proteins from non-conventional repeat translation have been recognized as important markers associated with the diseases. CRISPR/Cas13d, a powerful RNA-targeting tool, has faced challenges in effectively targeting RNA with stable secondary structures. Here we report that CRISPR/Cas13d can be optimized to specifically target GGGGCC repeat RNA. Our results demonstrate that the CRISPR/Cas13d system can be harnessed to significantly diminish the translation of poly-dipeptides originating from the GGGGCC repeat RNA. This efficacy has been validated in various cell types, including induced pluripotent stem cells and differentiated motor neurons originating from C9orf72-ALS patients, as well as in C9orf72 repeat transgenic mice. These findings demonstrate the application of CRISPR/Cas13d in targeting RNA with intricate higher-order structures and suggest a potential therapeutic approach for ALS and FTD.}, } @article {pmid39287680, year = {2024}, author = {Castelnovo, V and Canu, E and Aiello, EN and Curti, B and Sibilla, E and Torre, S and Freri, F and Tripodi, C and Lumaca, L and Spinelli, EG and Schito, P and Russo, T and Falzone, Y and Verde, F and Silani, V and Ticozzi, N and Sturm, VE and Rankin, KP and Gorno-Tempini, ML and Poletti, B and Filippi, M and Agosta, F}, title = {How to detect affect recognition alterations in amyotrophic lateral sclerosis.}, journal = {Journal of neurology}, volume = {271}, number = {11}, pages = {7208-7221}, pmid = {39287680}, issn = {1432-1459}, support = {StG-2016_714388_NeuroTRACK//FP7 Ideas: European Research Council/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/diagnosis/physiopathology ; Humans ; Male ; Female ; Middle Aged ; Aged ; *Neuropsychological Tests ; Recognition, Psychology/physiology ; Cognitive Dysfunction/diagnosis/etiology/physiopathology ; Reproducibility of Results ; }, abstract = {OBJECTIVE: To define the clinical usability of an affect recognition (AR) battery-the Comprehensive Affect Testing System (CATS)-in an Italian sample of patients with amyotrophic lateral sclerosis (ALS).

METHODS: 96 ALS patients and 116 healthy controls underwent a neuropsychological assessment including the AR subtests of the abbreviated version of the CATS (CATS-A). CATS-A AR subtests and their global score (CATS-A AR Quotient, ARQ) were assessed for their factorial, convergent, and divergent validity. The diagnostic accuracy of each CATS-A AR measure in discriminating ALS patients with cognitive impairment from cognitively normal controls and patients was tested via receiver-operating characteristics analyses. Optimal cut-offs were identified for CATS-A AR measures yielding an acceptable AUC value (≥ .70). The ability of CATS-A ARQ to discriminate between different ALS cognitive phenotypes was also tested. Gray-matter (GM) volumes of controls, ALS with normal (ALS-nARQ), and impaired ARQ score (ALS-iARQ) were compared using ANCOVA models.

RESULTS: CATS-A AR subtests and ARQ proved to have moderate-to-strong convergent and divergent validity. Almost all considered CATS-A measures reached acceptable accuracy and diagnostic power (AUC range = .79-.83). ARQ showed to be the best diagnostic measure (sensitivity = .80; specificity = .75) and discriminated between different ALS cognitive phenotypes. Compared to ALS-nARQ, ALS-iARQ patients showed reduced GM volumes in the right anterior cingulate, right middle frontal, left inferior temporal, and superior occipital regions.

CONCLUSIONS: The AR subtests of the CATS-A, and in particular the CATS-A ARQ, are sound measures of AR in ALS. AR deficits may be a valid marker of frontotemporal involvement in these patients.}, } @article {pmid39287519, year = {2024}, author = {Wendebourg, MJ and Kesenheimer, E and Sander, L and Weigel, M and Weidensteiner, C and Haas, T and Madoerin, P and Diebold, M and Deigendesch, N and Neuhaus, D and Naumann, N and Neuwirth, C and Braun, N and Weber, M and Granziera, C and Scheurer, E and Lenz, C and Schweikert, K and Sinnreich, M and Lieb, J and Bieri, O and Schlaeger, R}, title = {The Lateral Corticospinal Tract Sign: An MRI Marker for Amyotrophic Lateral Sclerosis.}, journal = {Radiology}, volume = {312}, number = {3}, pages = {e231630}, doi = {10.1148/radiol.231630}, pmid = {39287519}, issn = {1527-1315}, mesh = {Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; *Amyotrophic Lateral Sclerosis/diagnostic imaging ; *Magnetic Resonance Imaging/methods ; Prospective Studies ; *Pyramidal Tracts/diagnostic imaging/pathology ; Sensitivity and Specificity ; }, abstract = {Background Radially sampled averaged magnetization inversion-recovery acquisition (rAMIRA) imaging shows hyperintensity in the lateral corticospinal tract (CST) in patients with motor neuron diseases. Purpose To systematically determine the accuracy of the lateral corticospinal tract sign for detecting patients with amyotrophic lateral sclerosis (ALS) at rAMIRA MRI. Materials and Methods This study included prospectively acquired data from participants in ALS and other motor neuron disease imaging studies at the University Hospital Basel, Switzerland. All participants underwent 3-T axial two-dimensional rAMIRA imaging at four cervical intervertebral disk levels. The lateral CST sign was defined as spinal cord white matter hyperintensity dorsolateral to the anterior horns, with higher signal intensity than in the dorsal columns on axial rAMIRA images. Marker accuracy was assessed in a study data set and in an independent validation data set. Postmortem rAMIRA imaging and histopathologic analysis were performed in one participant who died during the study. Results Participants with ALS (study data set: 38 participants [mean age, 61 years; IQR, 15 years], 22 male participants; validation data set: 10 participants [mean age, 61 years; IQR, 21 years], seven male participants), post-polio syndrome (study data set: 25 participants [mean age, 68 years; IQR, 8 years], 12 male participants), spinal muscular atrophy (study data set: 10 participants [mean age, 43 years; IQR, 14 years], eight male participants; validation data set: five participants [mean age, 38 years; IQR, 19 years], two male participants), and healthy control participants (study data set: 60 participants [mean age, 57 years; IQR, 20 years], 36 male participants; validation data set: 10 participants [mean age, 44 years; IQR, 17 years], seven male participants) were included. The sensitivity and specificity of rAMIRA for ALS were 60% (23 of 38) and 97% (91 of 94) in the study data set and 100% (10 of 10) and 93% (14 of 15) in the validation data set, respectively. Histopathologic analysis showed distinct loss of myelinated axons in the localization of the hyperintensities observed at rAMIRA imaging performed in situ and after organ extraction. Conclusion The recently defined marker at rAMIRA MRI may be a promising tool for assessing upper motor neuron degeneration in the lateral CST in patients with ALS. Clinical trials registration no. NCT03561623, NCT05764434, NCT06137612 © RSNA, 2024 Supplemental material is available for this article.}, } @article {pmid39287472, year = {2024}, author = {Kasperkiewicz, M}, title = {Letter to the Editor: Comment on Bocanegra-Oyola et al's "Clinical Characteristics of Ocular Mucous Membrane Pemphigoid: A Systematic Review and Meta-Analysis".}, journal = {Ocular immunology and inflammation}, volume = {32}, number = {10}, pages = {2622-2623}, doi = {10.1080/09273948.2024.2404105}, pmid = {39287472}, issn = {1744-5078}, mesh = {Humans ; Diagnosis, Differential ; *Pemphigoid, Benign Mucous Membrane/diagnosis ; Meta-Analysis as Topic ; }, abstract = {The work by Bocanegra-Oyola et al. provides a qualitative analysis and meta-analysis of ocular pemphigoid characteristics. This correspondence discusses the need for diagnostic process optimization to better differentiate between ocular pemphigoid and its mimicker pseudopemphigoid.}, } @article {pmid39286440, year = {2024}, author = {Kew, SYN and Mok, SY and Goh, CH}, title = {Machine learning and brain-computer interface approaches in prognosis and individualized care strategies for individuals with amyotrophic lateral sclerosis: A systematic review.}, journal = {MethodsX}, volume = {13}, number = {}, pages = {102765}, pmid = {39286440}, issn = {2215-0161}, abstract = {Amyotrophic lateral sclerosis (ALS) characterized by progressive degeneration of motor neurons is a debilitating disease, posing substantial challenges in both prognosis and daily life assistance. However, with the advancement of machine learning (ML) which is renowned for tackling many real-world settings, it can offer unprecedented opportunities in prognostic studies and facilitate individuals with ALS in motor-imagery tasks. ML models, such as random forests (RF), have emerged as the most common and effective algorithms for predicting disease progression and survival time in ALS. The findings revealed that RF models had an excellent predictive performance for ALS, with a testing R2 of 0.524 and minimal treatment effects of 0.0717 for patient survival time. Despite significant limitations in sample size, with a maximum of 18 participants, which may not adequately reflect the population diversity being studied, ML approaches have been effectively applied to ALS datasets, and numerous prognostic models have been tested using neuroimaging data, longitudinal datasets, and core clinical variables. In many literatures, the constraints of ML models are seldom explicitly enunciated. Therefore, the main objective of this research is to provide a review of the most significant studies on the usage of ML models for analyzing ALS. This review covers a variation of ML algorithms involved in applications in ALS prognosis besides, leveraging ML to improve the efficacy of brain-computer interfaces (BCIs) for ALS individuals in later stages with restricted voluntary muscular control. The key future advances in individualized care and ALS prognosis may include the advancement of more personalized care aids that enable real-time input and ongoing validation of ML in diverse healthcare contexts.}, } @article {pmid39286389, year = {2024}, author = {Willman, M and Patel, G and Lucke-Wold, B}, title = {T lymphocyte proportion in Alzheimer's disease prognosis.}, journal = {World journal of clinical cases}, volume = {12}, number = {26}, pages = {6001-6003}, pmid = {39286389}, issn = {2307-8960}, abstract = {Bai et al investigate the predictive value of T lymphocyte proportion in Alzheimer's disease (AD) prognosis. Through a retrospective study involving 62 AD patients, they found that a decrease in T lymphocyte proportion correlated with a poorer prognosis, as indicated by higher modified Rankin scale scores. While the study highlights the potential of T lymphocyte proportion as a prognostic marker, it suggests the need for larger, multicenter studies to enhance generalizability and validity. Additionally, future research could use cognitive exams when evaluating prognosis and delve into immune mechanisms underlying AD progression. Despite limitations inherent in retrospective designs, Bai et al's work contributes to understanding the immune system's role in AD prognosis, paving the way for further exploration in this under-researched area.}, } @article {pmid39283513, year = {2025}, author = {Koopmann, A and Hoffmann, S and Riegler, A and Cordes, J and Kiefer, F}, title = {[Factors influencing hospital readmission rates in alcohol use disorder].}, journal = {Der Nervenarzt}, volume = {96}, number = {3}, pages = {278-283}, pmid = {39283513}, issn = {1433-0407}, mesh = {Humans ; *Patient Readmission/statistics & numerical data ; Male ; Female ; Middle Aged ; *Alcoholism/epidemiology/therapy/diagnosis/rehabilitation ; Germany/epidemiology ; Retrospective Studies ; Risk Factors ; Adult ; Comorbidity ; *Substance Withdrawal Syndrome/epidemiology ; Treatment Outcome ; Aged ; }, abstract = {BACKGROUND: According to data from the Federal Statistical Office, the diagnosis of alcohol use disorder (AUD) (F 10) is the second most common main diagnosis for hospital treatment. Those affected by this disorder are often repeatedly hospitalized at short intervals due to relapses; however, little is known about the factors that influence readmission rates after initial treatment.

AIM OF THE STUDY: The aim of this retrospective analysis is to analyze the effects of treatment type (qualified withdrawal treatment (QE) versus physical detoxification) and discharge mode on the probability of readmission in alcohol-dependent patients after inpatient treatment.

MATERIAL AND METHODS: Data from 981 male and female alcohol-dependent patients who completed either qualified withdrawal treatment (QE) (68% men; mean age 47.6 years) or inpatient detoxification (74% men; mean age 48.0 years) were analyzed. Predictors of regular discharge were determined separately for both types of treatment using stepwise logistic regression.

RESULTS: Patients who had completed a qualified withdrawal treatment were significantly more likely to be regularly discharged. Regular completion of the qualified withdrawal treatment (QE) led to a relative reduction in the readmission rate of 25.64% within 1 year compared to a physical detoxification.

CONCLUSION: In order to prevent readmission and chronic courses of alcohol use disorder (AUD), qualified withdrawal treatment should always be recommended to affected patients instead of physical detoxification. Aktuelle Daten des Statistischen Bundesamtes für das Jahr 2022 zeigen, dass die Diagnose "Psychische und Verhaltensstörungen durch Alkohol (F 10.X)" die zweithäufigste Hauptdiagnose bei Krankenhausbehandlungen darstellt [13]. Im Gesundheitssystem entstehen durch dieses Erkrankungsbild und seine somatischen und psychischen Folgeerkrankungen jährlich ca. 10 Mrd. € direkte Kosten [13]. Dieser Sachverhalt wird dadurch kontrastiert, dass die Krankenkassen die qualifizierte Entzugsbehandlung (QE) als leitliniengerechte Goldstandardtherapie [4] wiederholt infrage stellen [10].}, } @article {pmid39283487, year = {2024}, author = {Zufiría, M and Pikatza-Menoio, O and Garciandia-Arcelus, M and Bengoetxea, X and Jiménez, A and Elicegui, A and Levchuk, M and Arnold-García, O and Ondaro, J and Iruzubieta, P and Rodríguez-Gómez, L and Fernández-Pelayo, U and Muñoz-Oreja, M and Aiastui, A and García-Verdugo, JM and Herranz-Pérez, V and Zulaica, M and Poza, JJ and Ruiz-Onandi, R and Fernández-Torrón, R and Espinal, JB and Bonilla, M and Lersundi, A and Fernández-Eulate, G and Riancho, J and Vallejo-Illarramendi, A and Holt, IJ and Sáenz, A and Malfatti, E and Duguez, S and Blázquez, L and López de Munain, A and Gerenu, G and Gil-Bea, F and Alonso-Martín, S}, title = {Dysregulated FOXO1 activity drives skeletal muscle intrinsic dysfunction in amyotrophic lateral sclerosis.}, journal = {Acta neuropathologica}, volume = {148}, number = {1}, pages = {43}, pmid = {39283487}, issn = {1432-0533}, support = {CB06/05/1126//Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas/ ; PI2020/08-1//Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas/ ; P18/01066//Instituto de Salud Carlos III/ ; PI19/00175//Instituto de Salud Carlos III/ ; PI21/00153//Instituto de Salud Carlos III/ ; PI22/00433//Instituto de Salud Carlos III/ ; IJC2019-039965-I//Instituto de Salud Carlos III/ ; 2020-CIEN-000057-01//Diputación Foral de Gipuzkoa/ ; 2021-CIEN-000020-01//Diputación Foral de Gipuzkoa/ ; 2019-FELL-000010-01//Diputación Foral de Gipuzkoa/ ; 2020-FELL-000016-02-01//Diputación Foral de Gipuzkoa/ ; 2021-FELL-000013-02-01//Diputación Foral de Gipuzkoa/ ; BIO17/ND/023/BD//EiTB Maratoia/ ; 2015111122//Osasun Saila, Eusko Jaurlaritzako/ ; 2017222027//Osasun Saila, Eusko Jaurlaritzako/ ; 2018111042//Osasun Saila, Eusko Jaurlaritzako/ ; 2019222020//Osasun Saila, Eusko Jaurlaritzako/ ; 2020111032//Osasun Saila, Eusko Jaurlaritzako/ ; 2020333043//Osasun Saila, Eusko Jaurlaritzako/ ; 2021333050//Osasun Saila, Eusko Jaurlaritzako/ ; PRE_2015_1_0023//Hezkuntza, Hizkuntza Politika Eta Kultura Saila, Eusko Jaurlaritza/ ; PRE_2019_1_0339//Hezkuntza, Hizkuntza Politika Eta Kultura Saila, Eusko Jaurlaritza/ ; PRE_2020_1_0122//Hezkuntza, Hizkuntza Politika Eta Kultura Saila, Eusko Jaurlaritza/ ; PRE_2020_1_0191//Hezkuntza, Hizkuntza Politika Eta Kultura Saila, Eusko Jaurlaritza/ ; PRE_2020_1_0119//Hezkuntza, Hizkuntza Politika Eta Kultura Saila, Eusko Jaurlaritza/ ; PRE_2018_1_0095//Hezkuntza, Hizkuntza Politika Eta Kultura Saila, Eusko Jaurlaritza/ ; PRE_2021_1_0125//Hezkuntza, Hizkuntza Politika Eta Kultura Saila, Eusko Jaurlaritza/ ; PRE_2018_1_0253//Hezkuntza, Hizkuntza Politika Eta Kultura Saila, Eusko Jaurlaritza/ ; NEURODEGENPROT//Hezkuntza, Hizkuntza Politika Eta Kultura Saila, Eusko Jaurlaritza/ ; PIF18/317//Euskal Herriko Unibertsitatea/ ; RYC2018-024397-I//Spanish National Plan for Scientific and Technical Research and Innovation/ ; RF/2019/001//Ikerbasque, Basque Foundation for Science/ ; RF/2023/010//Ikerbasque, Basque Foundation for Science/ ; PP/2022/003//Ikerbasque, Basque Foundation for Science/ ; BIO19/ROCHE/017/BD//Roche España/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/metabolism/genetics/pathology ; Humans ; Animals ; *Muscle, Skeletal/metabolism/pathology ; *Forkhead Box Protein O1/metabolism/genetics ; DNA-Binding Proteins/genetics/metabolism ; Male ; RNA-Binding Protein FUS/genetics/metabolism ; Female ; Drosophila ; Muscle Development/physiology ; Middle Aged ; Aged ; Motor Neurons/metabolism/pathology ; Myoblasts/metabolism ; }, abstract = {Amyotrophic Lateral Sclerosis (ALS) is a multisystemic neurodegenerative disorder, with accumulating evidence indicating metabolic disruptions in the skeletal muscle preceding disease symptoms, rather than them manifesting as a secondary consequence of motor neuron (MN) degeneration. Hence, energy homeostasis is deeply implicated in the complex physiopathology of ALS and skeletal muscle has emerged as a key therapeutic target. Here, we describe intrinsic abnormalities in ALS skeletal muscle, both in patient-derived muscle cells and in muscle cell lines with genetic knockdown of genes related to familial ALS, such as TARDBP (TDP-43) and FUS. We found a functional impairment of myogenesis that parallels defects of glucose oxidation in ALS muscle cells. We identified FOXO1 transcription factor as a key mediator of these metabolic and functional features in ALS muscle, via gene expression profiling and biochemical surveys in TDP-43 and FUS-silenced muscle progenitors. Strikingly, inhibition of FOXO1 mitigated the impaired myogenesis in both the genetically modified and the primary ALS myoblasts. In addition, specific in vivo conditional knockdown of TDP-43 or FUS orthologs (TBPH or caz) in Drosophila muscle precursor cells resulted in decreased innervation and profound dysfunction of motor nerve terminals and neuromuscular synapses, accompanied by motor abnormalities and reduced lifespan. Remarkably, these phenotypes were partially corrected by foxo inhibition, bolstering the potential pharmacological management of muscle intrinsic abnormalities associated with ALS. The findings demonstrate an intrinsic muscle dysfunction in ALS, which can be modulated by targeting FOXO factors, paving the way for novel therapeutic approaches that focus on the skeletal muscle as complementary target tissue.}, } @article {pmid39282230, year = {2024}, author = {Tsai, YC and Brown, KA and Bernardi, MT and Harting, J and Clelland, CD}, title = {Single-Molecule Sequencing of the C9orf72 Repeat Expansion in Patient iPSCs.}, journal = {Bio-protocol}, volume = {14}, number = {17}, pages = {e5060}, pmid = {39282230}, issn = {2331-8325}, support = {K08 NS112330/NS/NINDS NIH HHS/United States ; U01 NS134062/NS/NINDS NIH HHS/United States ; U19 NS132303/NS/NINDS NIH HHS/United States ; }, abstract = {A hexanucleotide GGGGCC repeat expansion in the C9orf72 gene is the most frequent genetic cause of amyotrophic lateral sclerosis (ALS) and frontal temporal dementia (FTD). C9orf72 repeat expansions are currently identified with long-range PCR or Southern blot for clinical and research purposes, but these methods lack accuracy and sensitivity. The GC-rich and repetitive content of the region cannot be amplified by PCR, which leads traditional sequencing approaches to fail. We turned instead to PacBio single-molecule sequencing to detect and size the C9orf72 repeat expansion without amplification. We isolated high molecular weight genomic DNA from patient-derived iPSCs of varying repeat lengths and then excised the region containing the C9orf72 repeat expansion from naked DNA with a CRISPR/Cas9 system. We added adapters to the cut ends, capturing the target region for sequencing on PacBio's Sequel, Sequel II, or Sequel IIe. This approach enriches the C9orf72 repeat region without amplification and allows the repeat expansion to be consistently and accurately sized, even for repeats in the thousands. Key features • This protocol is adapted from PacBio's previous "no-amp targeted sequencing utilizing the CRISPR-Cas9 system." • Optimized for sizing C9orf72 repeat expansions in patient-derived iPSCs and applicable to DNA from any cell type, blood, or tissue. • Requires high molecular weight naked DNA. • Compatible with Sequel I and II but not Revio.}, } @article {pmid39281855, year = {2024}, author = {Jones, VM and Thompson, LDR and Pettus, JR and Green, DC and Lefferts, JA and Shah, PS and Tsongalis, GJ and Sajed, DP and Guilmette, JM and Lewis, JS and Fisch, AS and Tafe, LJ and Kerr, DA}, title = {Angiomyolipomatous Lesions of the Nasal Cavity (Sinonasal Angioleiomyoma with Adipocytic Differentiation): A Multi-Institutional Immunohistochemical and Molecular Study.}, journal = {Research square}, volume = {}, number = {}, pages = {}, pmid = {39281855}, issn = {2693-5015}, support = {P30 CA023108/CA/NCI NIH HHS/United States ; }, abstract = {PURPOSE: Mesenchymal neoplasms composed of vascular, smooth muscle, and adipocytic components are uncommon in the nasal cavity. While angioleiomyoma (AL) is a smooth muscle tumor in the Head & Neck WHO classification, it is considered of pericytic origin in the Skin as well as Soft Tissue and Bone classifications. For nasal AL with an adipocytic component, the terms AL with adipocytic differentiation and angiomyolipoma (AML) have been applied, among others. AML is a type of perivascular epithelioid cell tumor (PEComa), most often arising in the kidney, sometimes associated with the tuberous sclerosis complex (TSC). It is uncertain whether nasal cavity AML and AL are best considered hamartomas or neoplasms, as their genetics are largely unexplored.

METHODS: We performed a multi-institutional retrospective study of nasal cavity mesenchymal lesions. Patient demographics, clinical histories, and histologic and immunohistochemical findings were collected. DNA and RNA were extracted from formalin-fixed, paraffin-embedded tissue and analyzed by SNP-based chromosomal microarray, targeted RNA fusion sequencing, and whole-exome sequencing.

RESULTS: Fifteen lesions (3 to 42 mm) were identified predominantly in male (87%) patients with a median age of 60. Patients typically presented with obstructive symptoms, and none had a history of TSC. One AL was a recurrence from six years prior; 11 cases showed no recurrence (median 4.7 years, range: 0.88-12.4). Morphologically, 11 AMLs contained 30-80% smooth muscle, 10-25% vasculature, and 2-60% adipose tissue, while four ALs contained 70-80% smooth muscle and 20-30% vasculature. Other histologic observations included surface ulceration, vascular thrombosis, chronic inflammation, and myxoid change; no well-developed epithelioid cell morphology was identified. Immunohistochemically, all cases were positive for smooth muscle markers (actin and/or desmin) and negative for melanocytic markers. Molecular analysis revealed loss of 3p and 11q in a single AML. No other known pathogenic copy number or molecular alterations were seen, including in TSC1/2, TFE3, or NOTCH2.

CONCLUSION: Nasal cavity AML lacks morphologic, immunophenotypic, and genetic features of PEComa family AMLs. The significant histologic overlap between nasal AML and AL without distinguishing molecular features in either entity suggests "sinonasal angioleiomyoma with adipocytic differentiation" may be the most appropriate terminology for hybrid vascular and smooth muscle lesions containing adipocytic components.}, } @article {pmid39280885, year = {2024}, author = {Robinson, SE and Findlay, AR and Li, S and Wang, F and Schiava, M and Daw, J and Diaz-Manera, J and Chou, TF and Weihl, CC}, title = {Elevated VCP ATPase Activity Correlates With Disease Onset in Multisystem Proteinopathy-1.}, journal = {Neurology. Genetics}, volume = {10}, number = {5}, pages = {e200191}, pmid = {39280885}, issn = {2376-7839}, support = {K24 AR073317/AR/NIAMS NIH HHS/United States ; R01 AG031867/AG/NIA NIH HHS/United States ; }, abstract = {OBJECTIVES: Multisystem proteinopathy-1 (MSP1) is a late onset disease with >50 pathogenic variants in p97/VCP. MSP1 patients have multiple phenotypes that include inclusion body myopathy, Paget disease of the bone, amyotrophic lateral sclerosis, and frontotemporal dementia. There have been no clear genotype-phenotype correlations. We sought to identify genotype-phenotype correlations and associate these with VCP intrinsic ATPase activity.

METHODS: Patients with MSP1 were identified from the literature and the Cure VCP patient registry. Age at onset and at loss of ambulation were collated. VCP intrinsic ATPase activity was evaluated from recombinant purified protein.

RESULTS: Among the 5 most common pathogenic VCP variants in MSP1 patients, R155C patients had the earliest average age at onset (38.15 ± 9.78). This correlated with higher ATPase activity. Evaluation of 5 variants confirmed an inverse correlation between age at onset and ATPase activity (r = -0.94, p = 0.01).

DISCUSSION: Previous studies have reported that VCP pathogenic variants are "hyperactive." Whether this elevation in VCP ATPase activity is relevant to disease is unclear. Our study supports that in vitro VCP activity correlates with disease onset and may guide the prognosis of patients with rare or unreported variants. Moreover, it suggests that inhibition of VCP ATPase activity in MSP1 may be therapeutic.}, } @article {pmid39280794, year = {2024}, author = {Ren, K and Wang, Q and Jiang, D and Liu, E and Alsmaan, J and Jiang, R and Rutkove, SB and Tian, F}, title = {A comprehensive review of electrophysiological techniques in amyotrophic lateral sclerosis research.}, journal = {Frontiers in cellular neuroscience}, volume = {18}, number = {}, pages = {1435619}, pmid = {39280794}, issn = {1662-5102}, support = {R01 NS055099/NS/NINDS NIH HHS/United States ; }, abstract = {Amyotrophic lateral sclerosis (ALS), a devastating neurodegenerative disease, is characterized by progressive motor neuron degeneration, leading to widespread weakness and respiratory failure. While a variety of mechanisms have been proposed as causes of this disease, a full understanding remains elusive. Electrophysiological alterations, including increased motor axon excitability, likely play an important role in disease progression. There remains a critical need for non-animal disease models that can integrate electrophysiological tools to better understand underlying mechanisms, track disease progression, and evaluate potential therapeutic interventions. This review explores the integration of electrophysiological technologies with ALS disease models. It covers cellular and clinical electrophysiological tools and their applications in ALS research. Additionally, we examine conventional animal models and highlight advancements in humanized models and 3D organoid technologies. By bridging the gap between these models, we aim to enhance our understanding of ALS pathogenesis and facilitate the development of new therapeutic strategies.}, } @article {pmid39280372, year = {2024}, author = {Nishiwaki, T and Oya, A and Fujie, A and Kanaji, A}, title = {Higher Incidence of Venous Thromboembolism in Anterolateral Approach in Lateral Position Compared to Anterolateral Supine and Direct Anterior Approaches in Minimally Invasive Total Hip Arthroplasty.}, journal = {Cureus}, volume = {16}, number = {8}, pages = {e66831}, pmid = {39280372}, issn = {2168-8184}, abstract = {INTRODUCTION: Venous thromboembolism (VTE) remains a major complication after total hip arthroplasty (THA), irrespective of the surgical approach. This study investigated the incidence of VTE in patients undergoing THA through intermuscular minimally invasive surgical techniques, which included a direct anterior approach (DAA), an anterolateral approach (AL), and an anterolateral supine approach (ALS), at a single institution.

METHODS: A hundred consecutive patients treated with each surgical approach were evaluated. Plasma D-dimer levels one month preoperatively and one day postoperatively, operative time, and intraoperative blood loss were recorded, and the presence of VTE was evaluated based on multidetector-row computed tomography performed the day after surgery. Student's t-test and Pearson's chi-square test or one-way analysis of variance were used in statistical analysis.

RESULTS: No differences among the groups in terms of age, height, weight, operative time, intraoperative bleeding, and preoperative and postoperative D-dimer levels were observed. The overall incidence of VTE was 21%. The incidences of VTE were 30% in AL, 17% in ALS, and 16% in DAA, representing a significantly higher rate in AL than in ALS and DAA (P=0.025). The incidences of VTE on the operated side were 19% in AL, 13% in ALS, and 12% in DAA, with no statistically significant differences. The incidences of VTE on the non-operated side were 22% in AL, 9% in ALS, and 8% in DAA; these differences were statistically significant (P=0.0045).

DISCUSSION: Results showed that the incidence of VTE was significantly higher in AL than in ALS and DAA, especially for the non-operated side.}, } @article {pmid39280119, year = {2024}, author = {Banack, SA and Dunlop, RA and Mehta, P and Mitsumoto, H and Wood, SP and Han, M and Cox, PA}, title = {A microRNA diagnostic biomarker for amyotrophic lateral sclerosis.}, journal = {Brain communications}, volume = {6}, number = {5}, pages = {fcae268}, pmid = {39280119}, issn = {2632-1297}, abstract = {Blood-based diagnostic biomarkers for amyotrophic lateral sclerosis will improve patient outcomes and positively impact novel drug development. Critical to the development of such biomarkers is robust method validation, optimization and replication with adequate sample sizes and neurological disease comparative blood samples. We sought to test an amyotrophic lateral sclerosis biomarker derived from diverse samples to determine if it is disease specific. Extracellular vesicles were extracted from blood plasma obtained from individuals diagnosed with amyotrophic lateral sclerosis, primary lateral sclerosis, Parkinson's disease and healthy controls. Immunoaffinity purification was used to create a neural-enriched extracellular vesicle fraction. MicroRNAs were measured across sample cohorts using real-time polymerase chain reaction. A Kruskal-Wallis test was used to assess differences in plasma microRNAs followed by post hoc Mann-Whitney tests to compare disease groups. Diagnostic accuracy was determined using a machine learning algorithm and a logistic regression model. We identified an eight-microRNA diagnostic signature for blood samples from amyotrophic lateral sclerosis patients with high sensitivity and specificity and an area under the curve calculation of 98% with clear statistical separation from neurological controls. The eight identified microRNAs represent disease-related biological processes consistent with amyotrophic lateral sclerosis. The direction and magnitude of gene fold regulation are consistent across four separate patient cohorts with real-time polymerase chain reaction analyses conducted in two laboratories from diverse samples and sample collection procedures. We propose that this diagnostic signature could be an aid to neurologists to supplement current clinical metrics used to diagnose amyotrophic lateral sclerosis.}, } @article {pmid39279312, year = {2024}, author = {Banaszak-Ziemska, M and Rojek, A and Niedziela, M}, title = {Genetic analysis of the PAPP-A2 gene and evaluation of free IGF-1, IGFBP-5, and ALS concentrations in a group of 22 patients with idiopathic short stature.}, journal = {Endokrynologia Polska}, volume = {75}, number = {4}, pages = {428-437}, doi = {10.5603/ep.100030}, pmid = {39279312}, issn = {2299-8306}, mesh = {Humans ; *Pregnancy-Associated Plasma Protein-A/genetics/metabolism/analysis ; Female ; *Insulin-Like Growth Factor I/genetics/analysis/metabolism ; Male ; Child ; Adolescent ; *Insulin-Like Growth Factor Binding Protein 5/genetics ; Carrier Proteins/genetics ; Glycoproteins/genetics/blood ; Growth Disorders/genetics/blood ; Mutation ; Child, Preschool ; }, abstract = {INTRODUCTION: Short stature is one of the main reasons for consultation in outpatient clinics and paediatric endocrinology departments and is defined as height below the 3rd centile or less than -2 standard deviations (SDs).

MATERIAL AND METHODS: The study's overarching aim was to analyse the PAPP-A2 gene at mutation sites described to date and at exons 3, 4, and 5, which encode the fragment of the catalytic domain with the active site of the pregnancy-associated plasma protein A2 (PAPP-A2) protein. The secondary aims of the study were clinical and auxological analysis of a group of patients with idiopathic short stature and biochemical analysis of growth hormone-insulin-like growth factor-1 (GH-IGF-1) axis parameters not assessed as part of the routine diagnosis of short stature, such as free IGF-1, insulin-like growth factor binding protein 5 (IGFBP-5), and acid-labile subunit (ALS) levels. Molecular analysis of the PAPP-A2 gene was performed using polymerase chain reaction (PCR) and direct sequencing. Biochemical analysis of free IGF-1, IGFBP-5, and ALS was performed by enzyme-linked immunosorbent assay (ELISA).

RESULTS: The mean height standard deviation score (HSDS) in the study group was -2.95. None of the patients exhibited previously described mutations in the PAPP-A2 gene or mutations in exons 3, 4, and 5 encoding the fragment of catalytic domain with the active site of the PAPP-A2 protein. In 4 patients, the known, non-pathogenic, heterozygotic polymorphism c.2328C>T(rs10913241) in exon 5 was found.

CONCLUSIONS: Free IGF-1 levels correlate better with height and HSDS than total IGF-1 levels. The previously described mutations in the PAPP-A2 gene and mutations in exons 3, 4, and 5 encoding the fragment of catalytic domain with the active site of the PAPP-A2 protein were not detected; only the known and non-pathogenic, heterozygotic polymorphism c.2328C>T(rs10913241) in exon 5 of the PAPP-A2 gene was observed.}, } @article {pmid39279053, year = {2024}, author = {Lin, PH and Yao, HY and Huang, L and Fu, CC and Yao, XL and Lian, C and Zhang, SF and Lai, WD and Lin, GY and Liao, S and Yang, J and Mao, ZF and Liu, D and Long, BY and Yue, JJ and Gao, C and Long, YM}, title = {Autoimmune astrocytopathy double negative for AQP4-IgG and GFAP-IgG: Retrospective research of clinical practice, biomarkers, and pathology.}, journal = {CNS neuroscience & therapeutics}, volume = {30}, number = {9}, pages = {e70042}, pmid = {39279053}, issn = {1755-5949}, support = {2022A1515110143//Basic and Applied Basic Research Foundation of Guangdong Province/ ; 2023A1515010225//Basic and Applied Basic Research Foundation of Guangdong Province/ ; 2022-LCYJ-YYDZX-04//Multi-center Project of The Second Affiliated Hospital of Guangzhou Medical University/ ; }, mesh = {Humans ; *Glial Fibrillary Acidic Protein/cerebrospinal fluid/immunology ; Female ; Male ; *Aquaporin 4/immunology ; Middle Aged ; *Astrocytes/immunology/metabolism/pathology ; Retrospective Studies ; Adult ; *Biomarkers/cerebrospinal fluid/blood ; Aged ; *Immunoglobulin G/cerebrospinal fluid/blood ; Neurofilament Proteins/cerebrospinal fluid/blood ; Autoantibodies/cerebrospinal fluid/blood ; Young Adult ; Adolescent ; }, abstract = {OBJECTIVE: The objective of this study is to investigate the presence of astrocyte antibodies in patients, excluding aquaporin-4 or glial fibrillary acidic protein (GFAP) antibodies, while evaluating associated biomarkers and pathologies.

METHODS: Patient serum and cerebrospinal fluid (CSF) were tested for antibodies using tissue- and cell-based assays. Neurofilament light chain (NFL) and GFAP in the CSF were detected using single-molecule array (SIMOA).

RESULTS: 116 patients accepted SIMOA. Fifteen functional neurological disorders patients without antibodies were designated as controls. Thirty-five patients were positive for astrocyte antibodies (Anti-GFAP: 7; Anti-AQP4: 7; unknown antibodies: 21, designed as the double-negative group, DNAP). The most frequent phenotype of DNAP was encephalitis (42.9%), followed by myelitis (23.8%), movement disorders (19.0%), and amyotrophic lateral sclerosis-like (ALS-like) disease (14.2%). The levels of CSF GFAP and NFL in DNAP were higher than in the control (GFAP: 1967.29 [776.60-13214.47] vs 475.38 [16.80-943.60] pg/mL, p < 0.001; NFL: 549.11 [162.08-2462.61] vs 214.18 [81.60-349.60] pg/mL, p = 0.002). GFAP levels decreased in DNAP (n = 5) after immunotherapy (2446.75 [1583.45-6277.33] vs 1380.46 [272.16-2005.80] pg/mL, p = 0.043), while there was no difference in NFL levels (2273.78 [162.08-2462.61] vs 890.42 [645.06-3168.06] pg/mL, p = 0.893). Two brain biopsy patterns were observed: one exhibited prominent tissue proliferation and hypertrophic astrocytes, with local loss of astrocytes, while the other showed severe astrocyte depletion with loss of neurofilaments around the vessels. Eighteen patients received immunotherapy, and improved except one with ALS-like symptoms. We identified anti-vimentin in this patient.

DISCUSSION: There are unidentified astrocyte antibodies. The manifestations of double-negativity are heterogeneous; nevertheless, the pathology and biomarkers remain consistent with astrocytopathy. Immunotherapy is effective.}, } @article {pmid39278909, year = {2024}, author = {Reis, ALG and Maximino, JR and Lage, LAPC and Gomes, HR and Pereira, J and Brofman, PRS and Senegaglia, AC and Rebelatto, CLK and Daga, DR and Paiva, WS and Chadi, G}, title = {Proteomic analysis of cerebrospinal fluid of amyotrophic lateral sclerosis patients in the presence of autologous bone marrow derived mesenchymal stem cells.}, journal = {Stem cell research & therapy}, volume = {15}, number = {1}, pages = {301}, pmid = {39278909}, issn = {1757-6512}, support = {401922/2014-6//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; 836458/2016//Ministério da Saúde/ ; 1701/22//Financiadora de Estudos e Projetos/ ; }, mesh = {Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; *Amyotrophic Lateral Sclerosis/cerebrospinal fluid/therapy/metabolism ; Apolipoprotein A-I/cerebrospinal fluid/metabolism ; Apolipoproteins E/metabolism/genetics/cerebrospinal fluid ; Bone Marrow Cells/metabolism ; *Mesenchymal Stem Cell Transplantation/methods ; *Mesenchymal Stem Cells/metabolism ; Protein Interaction Maps ; *Proteomics/methods ; *Transplantation, Autologous ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a fatal and rapidly progressive motoneuron degenerative disorder. There are still no drugs capable of slowing disease evolution or improving life quality of ALS patients. Thus, autologous stem cell therapy has emerged as an alternative treatment regime to be investigated in clinical ALS.

METHOD: Using Proteomics and Protein-Protein Interaction Network analyses combined with bioinformatics, the possible cellular mechanisms and molecular targets related to mesenchymal stem cells (MSCs, 1 × 10[6] cells/kg, intrathecally in the lumbar region of the spine) were investigated in cerebrospinal fluid (CSF) of ALS patients who received intrathecal infusions of autologous bone marrow-derived MSCs thirty days after cell therapy. Data are available via ProteomeXchange with identifier PXD053129.

RESULTS: Proteomics revealed 220 deregulated proteins in CSF of ALS subjects treated with MSCs compared to CSF collected from the same patients prior to MSCs infusion. Bioinformatics enriched analyses highlighted events of Extracellular matrix and Cell adhesion molecules as well as related key targets APOA1, APOE, APP, C4A, C5, FGA, FGB, FGG and PLG in the CSF of cell treated ALS subjects.

CONCLUSIONS: Extracellular matrix and cell adhesion molecules as well as their related highlighted components have emerged as key targets of autologous MSCs in CSF of ALS patients.

TRIAL REGISTRATION: Clinicaltrial.gov identifier NCT0291768. Registered 28 September 2016.}, } @article {pmid39277385, year = {2024}, author = {Porri, A and Panozzo, S and Tekeste Sisay, M and Scarabel, L and Lerchl, J and Milani, A}, title = {3D structure of acetolactate synthase explains why the Asp-376-Glu point mutation does not give the same resistance level to different imidazolinone herbicides.}, journal = {Pesticide biochemistry and physiology}, volume = {204}, number = {}, pages = {106070}, doi = {10.1016/j.pestbp.2024.106070}, pmid = {39277385}, issn = {1095-9939}, mesh = {*Acetolactate Synthase/genetics/metabolism/chemistry ; *Herbicides/pharmacology/chemistry ; *Herbicide Resistance/genetics ; *Imidazoles/pharmacology/chemistry ; *Amaranthus/drug effects/genetics ; *Point Mutation ; Sorghum/genetics/drug effects ; Molecular Docking Simulation ; Plant Proteins/genetics/metabolism/chemistry ; Nicotinic Acids/pharmacology ; Niacin/analogs & derivatives ; }, abstract = {Resistance to ALS-inhibiting herbicides has dramatically increased worldwide due to the persisting evolution of target site mutations that reduce the affinity between the herbicide and the target. We evaluated the effect of the well-known ALS Asp-376-Glu target site mutation on different imidazolinone herbicides, including imazamox and imazethapyr. Greenhouse dose response experiments indicate that the Amaranthus retroflexus biotype carrying Asp-376-Glu was fully controlled by applying the field recommended dose of imazamox, whereas it displayed high level of resistance to imazethapyr. Likewise, Sorghum halepense, carrying Asp-376-Glu showed resistance to field recommended doses of imazethapyr but not of imazamox. Biochemical inhibition and kinetic characterization of the Asp-376-Glu mutant enzyme heterologously expressed using different plant sequence backbones, indicate that the Asp-376-Glu shows high level of insensitivity to imazethapyr but not to imazamox, corroborating the greenhouse results. Docking simulations revealed that imazamox can still inhibit the Asp-376-Glu mutant enzyme through a chalcogen interaction between the oxygen of the ligand and the sulfur atom of the ALS Met200, while imazethapyr does not create such interaction. These results explain the different sensitivity of the Asp-376-Glu mutation towards imidazolinone herbicides, thus providing novel information that can be exploited for defining stewardship guidelines to manage fields infested by weeds harboring the Asp-376-Glu mutation.}, } @article {pmid39277366, year = {2024}, author = {Weng, WF and Yao, X and Zhao, M and Fang, Z and Yang, S and Ruan, JJ}, title = {Novel mutations in acetolactate synthase confer high levels of resistance to tribenuron-methyl in Fagopyrum tataricum.}, journal = {Pesticide biochemistry and physiology}, volume = {204}, number = {}, pages = {106039}, doi = {10.1016/j.pestbp.2024.106039}, pmid = {39277366}, issn = {1095-9939}, mesh = {*Acetolactate Synthase/genetics/metabolism ; *Fagopyrum/genetics/drug effects ; *Herbicide Resistance/genetics ; *Herbicides/pharmacology ; *Arylsulfonates/pharmacology ; *Mutation ; Plant Proteins/genetics/metabolism ; }, abstract = {Tartary buckwheat (Fagopyrum tataricum) field weeds are rich in species, with many weeds causing reduced quality, yield, and crop failure. The selection of herbicide-resistant Tartary buckwheat varieties, while applying low-toxicity and efficient herbicides as a complementary weed control system, is one way to improve Tartary buckwheat yield and quality. Therefore, the development of herbicide-resistant varieties is important for the breeding of Tartary buckwheat. In this experiment, 50 mM ethyl methyl sulfonate solution was used to treat Tartary buckwheat seeds (M1) and then planted in the field. Harvested seeds (M2) were planted in the experiment field of Guizhou University, and when seedlings had 5-7 leaves, the seedlings were sprayed with 166 mg/L tribenuron-methyl (TBM). A total of 15 resistant plants were obtained, of which three were highly resistant. Using the homologous cloning method, an acetolactate synthase (ALS) gene encoding 547 amino acids was identified in Tartary buckwheat. A GTG (valine) to GGA (glycine) mutation (V409G) occurred at position 409 of the ALS gene in the high tribenuron-methyl resistant mutant sm113. The dm36 mutant harbored a double mutation, a deletion mutation at position 405, and a GTG (valine) to GGA (glycine) mutation (V411G) at position 411. The dm110 mutant underwent a double mutation: an ATG (methionine) to AGG (arginine) mutation (M333R) at position 333 and an insertion mutation at position 372. The synthesis of Chl a, Chl b, total Chl, and Car was significantly inhibited by TBM treatment. TBM was more efficient at suppressing the growth of wild-type plants than that of mutant plants. Antioxidant enzyme activities such as ascorbate peroxidase, peroxidase, and superoxide dismutase were significantly higher in resistant plants than in wild-type after spraying with TBM; malondialdehyde content was significantly lower than in wild-type plants after spraying with TBM. Plants with a single-site mutation in the ALS gene could survive, but their growth was affected by herbicide application. In contrast, plants with dual-site mutations in the ALS gene were not affected, indicating that plants with dual-site mutations in the ALS gene showed higher levels of resistance than plants with a single-site mutation in the ALS gene.}, } @article {pmid39277365, year = {2024}, author = {Guan, Y and Liu, L and Zou, Y and Yang, C and Ji, M}, title = {Involvement of P450s in the metabolic resistance of Digitaria sanguinalis (L.) Scop. To ALS-inhibiting herbicides.}, journal = {Pesticide biochemistry and physiology}, volume = {204}, number = {}, pages = {106038}, doi = {10.1016/j.pestbp.2024.106038}, pmid = {39277365}, issn = {1095-9939}, mesh = {*Herbicides/pharmacology/toxicity ; *Acetolactate Synthase/metabolism/genetics/antagonists & inhibitors ; *Herbicide Resistance/genetics ; *Cytochrome P-450 Enzyme System/metabolism/genetics ; *Digitaria/drug effects ; Sulfonylurea Compounds/pharmacology ; Plant Weeds/drug effects/metabolism ; Plant Proteins/genetics/metabolism ; Pyridines ; }, abstract = {Weed resistance to a range of herbicides has rapidly evolved, often with different mechanisms of action. The resulting uninhibited growth of weeds poses demonstrable threats to crop production and sustainable agriculture. Digitaria sanguinalis (L.) Scop., a troublesome weed in corn and other agricultural fields, has developed resistance to herbicides that inhibiting ALS (Acetolactate Synthase), such as nicosulfuron. Understanding the weed's resistance patterns and mechanisms is crucial. However, little is known of the non-target site resistance (NTSR) mechanisms of D. sanguinalis owing to a lack of relevant genome sequences and other materials. Therefore, in this study, a population of D.sanguinalis presenting multiple resistance was tested and found that its high level of resistance to ALS-inhibiting herbicides was not associated with target-related alterations.Administration of P450 inhibitors reversed the resistance to ALS-inhibiting herbicides. Following the application of ALS-inhibiting herbicides, the activities of NADPH-P450 reductase and p-nitroanisole O-demethylase (PNOD) were notably greater in the resistant population of D. sanguinalis than those in the susceptible population. The results suggested P450 enzyme familyplays a major role in the metabolic resistance mechanism, that increased P450 enzyme activity promote cross-resistance in D. sanguinalis to ALS-inhibiting herbicides. RNA-seq analysis showed that five genes from the P450 family (CYP709B2, CYP714C2, CYP71A1, CYP76C2, and CYP81E8) were upregulated in resistant D. sanguinalis. In conclusion, the upregulation of several P450 genes is responsible for establishing resistance to ALS-inhibiting herbicides in D. sanguinalis.}, } @article {pmid39277361, year = {2024}, author = {Liu, L and Zou, Y and Guan, Y and Yang, C and Ji, M}, title = {Diverse mechanisms confer bensulfuron-methyl resistance in Schoenoplectiella juncoides (Roxb.) lye.}, journal = {Pesticide biochemistry and physiology}, volume = {204}, number = {}, pages = {106034}, doi = {10.1016/j.pestbp.2024.106034}, pmid = {39277361}, issn = {1095-9939}, mesh = {*Sulfonylurea Compounds/pharmacology ; Herbicide Resistance/genetics ; Herbicides/pharmacology ; Mutation ; Glutathione Transferase/metabolism/genetics ; }, abstract = {The effectiveness of bensulfuron-methyl in controlling Schoenoplectiella juncoides (Roxb.) Lye has significantly decreased in rice fields in China. Hence, a bensulfuron-methyl-resistant S. juncoides population (W15) was collected from Dandong City, Liaoning Province, China, to investigate the underlying resistance mechanisms. Whole-plant dose-response experiments and ALS activity assay confirmed that W15 has evolved high-level resistance to bensulfuron-methyl compared with the susceptible S. juncoides population (W4). Molecular analysis revealed a Pro-197-Ser mutation in ALS1, while there was no significant difference in the relative ALS gene expression between W15 and W4. LC-MS/MS analysis showed W15 metabolized bensulfuron-methyl more rapidly than W4. Furthermore, bensulfuron-methyl resistance in W15 was significantly alleviated by malathion and 4-chloro-7-nitrobenzoxadiazole (NBD-Cl). Glutathione S-transferase activity was higher in W15 than in W4. Meanwhile, W15 displayed cross-resistance to halosulfuron-methyl and multi-resistance to MCPA-Na. In summary, these findings demonstrated for the first time that both target- and non-target-site resistance are relevant in the resistance of S. juncoides to bensulfuron-methyl.}, } @article {pmid39268612, year = {2025}, author = {Meyer, T and Schumann, P and Grehl, T and Weyen, U and Petri, S and Rödiger, A and Steinbach, R and Grosskreutz, J and Bernsen, S and Weydt, P and Wolf, J and Günther, R and Vidovic, M and Baum, P and Metelmann, M and Weishaupt, JH and Streubel, B and Kasper, DC and Koc, Y and Kettemann, D and Norden, J and Schmitt, P and Walter, B and Münch, C and Spittel, S and Maier, A and Körtvélyessy, P}, title = {SOD1 gene screening in ALS - frequency of mutations, patients' attitudes to genetic information and transition to tofersen treatment in a multi-center program.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {26}, number = {1-2}, pages = {162-171}, doi = {10.1080/21678421.2024.2401131}, pmid = {39268612}, issn = {2167-9223}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/drug therapy ; *Superoxide Dismutase-1/genetics ; Male ; Female ; *Genetic Testing/methods ; Middle Aged ; *Mutation/genetics ; Aged ; Germany ; Adult ; C9orf72 Protein/genetics ; RNA-Binding Protein FUS/genetics ; }, abstract = {OBJECTIVE: To report the frequency of pathogenic SOD1 gene variants in a screening program in amyotrophic lateral sclerosis (ALS), and the clinical practice of transition to an expanded access program (EAP) of tofersen treatment.

METHODS: From October 2021 to February 2024, at 11 ALS centers in Germany genetic testing for SOD1, FUS, TARDBP, and C9orf72 was performed. Patients were offered to opt for notification either about all genetic variants or SOD1 variants relevant for tofersen therapy. The transition to the EAP with tofersen was assessed.

RESULTS: 1935 patients were screened (94.7% sporadic ALS). 48.8% (n = 928) opted for notification of treatment-relevant information. Genetic variants were found as follows: SOD1 (likely) pathogenic variants (class 4/5) 1.8% (n = 34), variants of unknown significance (class 3) 0.8% (n = 16), FUS (class 4/5) 0.9% (n = 17), TARDBP (class 4/5) 1.3% (n = 25), C9orf72 hexanucleotide repeat expansion 7.0% (n = 135). In SOD1-ALS (encompassing class 3-5 variants, n = 50), 68.0% (n = 34) reported a negative family history. 74.0% (n = 37) of SOD1-ALS patients - which represent 1.9% of all participants of the screening program - were transitioned to tofersen. Median duration from start of genetic testing to treatment was 94 days (57 to 295 days). Eight patients declined treatment whereas five individuals died before initiation of therapy.

CONCLUSION: The finding of SOD1 variants in patients with a negative family history underscores the need for a broad genetic screening in ALS. In SOD1-ALS, the treatment option with tofersen was mostly utilized. The wide range in the transition time to tofersen calls for a SOD1-ALS management program.}, } @article {pmid39276073, year = {2025}, author = {Raymond, J and Berry, JD and Larson, T and Horton, DK and Mehta, P}, title = {Effects of COVID-19 on motor neuron disease mortality in the United States: a population-based cross-sectional study.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {26}, number = {1-2}, pages = {149-156}, doi = {10.1080/21678421.2024.2401621}, pmid = {39276073}, issn = {2167-9223}, mesh = {Humans ; *COVID-19/epidemiology/mortality ; *Motor Neuron Disease/mortality/epidemiology ; United States/epidemiology ; Male ; Female ; Middle Aged ; Aged ; Adult ; Cross-Sectional Studies ; Aged, 80 and over ; Young Adult ; SARS-CoV-2 ; }, abstract = {BACKGROUND: In March 2020, the World Health Organization declared the coronavirus disease 2019 (COVID-19) to be a pandemic, stating that those with underlying health conditions are most susceptible, including motor neuron disease (MND).

OBJECTIVE: To examine the effect the COVID-19 pandemic had on deaths from MND in the United States.

METHODS: Death certificate data for all MND deaths aged 20 years and older were analyzed from 2017 to 2019 (pre-COVID), then expanded to include 2020 and 2021 (COVID) deaths to evaluate if COVID-19 impacted MND deaths.

RESULTS: The average number of MND deaths documented during the COVID-19 years was 8009, up from 7485 MND deaths pre-COVID. The age-adjusted mortality rate among the non-Hispanic population increased during COVID to 2.78 per 100,000 persons (95% CI = 2.73-2.82) from 1.81 (95% CI = 1.78-1.84). The Hispanic population also saw an increase in mortality rate during COVID (1.61, 95% CI = 1.51-1.71) compared with pre-COVID (1.10, 95% CI = 1.03-1.17). Decedent's home as a place of death also saw a mortality rate increase during COVID (1.51, 95% CI = 1.48-1.54) compared with pre-COVID (1.30, 95% CI = 1.27-1.32). For the Hispanic population, the rate peaked at 80-84 years pre-COVID, but for the COVID years, the rate peaked earlier, at 75-79 years.

CONCLUSION: The total number of MND deaths was greater during COVID than in the preceding years. The analysis suggests there might have been a consequence of circumstances surrounding the global pandemic and the associated restrictions.}, } @article {pmid39275316, year = {2024}, author = {Hamm, JD and Laferrère, B and Albu, JB and Kini, S and Pi-Sunyer, X and Kissileff, HR}, title = {Responsiveness and Reliability of a Sipping Device to Measure Motivation in Normal-Weight Individuals and Bariatric Surgery Patients.}, journal = {Nutrients}, volume = {16}, number = {17}, pages = {}, pmid = {39275316}, issn = {2072-6643}, support = {R01 DK108643/DK/NIDDK NIH HHS/United States ; }, mesh = {Humans ; *Motivation ; *Bariatric Surgery ; Female ; Male ; Adult ; Reproducibility of Results ; Middle Aged ; Obesity/surgery/psychology ; Taste ; Beverages ; Sweetening Agents ; Feeding Behavior/psychology ; }, abstract = {There is an urgent need to measure the motivation to taste a sweet fluid in order to determine the influence of sweet tastes on the potential choices and consumption of beverages in patients with obesity. Current methods utilize either survey instruments or arbitrary operant tasks. The sipometer enables the participant to utilize an actual ingestive behavioral response to measure motivation during access to beverages on either ad libitum (AL) or progressive time ratio (PR) schedules. We determined the sipometer's responsiveness and reliability as a test of change in motivation for sweet tastes after bariatric surgery. Participants (58 patients and 28 controls, BMI: 18.5-24.9 kg/m[2]) sham-consumed an aspartame-sweetened (S) and non-sweetened (N) beverage under AL and PR schedules at a pre-surgery/baseline and a 3-month and 24-month visit (patients only). Cumulative pressure (CumPres), a measure of effort, was the sum of the pressures exerted during sipping under each condition. Baseline CumPres for PRS was higher than ALS and ALN in patients (p < 0.03) and higher than PRN in controls (p = 0.009). At 3 months, CumPres did not differ amongst conditions in patients, but CumPres for PRS was higher than all other conditions in controls (p < 0.0005). There were no baseline group differences; however, patients' CumPres for PRS was lower than controls' at 3 months (p = 0.002). Patients' CumPres for PRS decreased non-significantly between the baseline and 3 months but increased at 24 months compared to 3 months (p = 0.025) and was no different from baseline. Controls' CumPres for PRS increased at 3 months (p = 0.0359), but CumPres for all conditions was correlated between visits (p's < 0.038). The sipometer is a reliable and sensitive measure of motivation to consume sweet beverages and may reflect changes in post-operative energy intake.}, } @article {pmid39273978, year = {2024}, author = {Wu, Z and Liu, S and Zhang, X and Qian, X and Chen, Z and Zhao, H and Wan, H and Yin, N and Li, J and Qu, C and Du, H}, title = {Genome-Wide Characterization of Alfin-like Genes in Brassica napus and Functional Analyses of BnaAL02 and BnaAL28 in Response to Nitrogen and Phosphorus Deficiency.}, journal = {Plants (Basel, Switzerland)}, volume = {13}, number = {17}, pages = {}, pmid = {39273978}, issn = {2223-7747}, support = {32072094//National Key Research and Development Program of China/ ; 2023NSCQ-MSX3166//Natural Science Foundation of Chongqing/ ; }, abstract = {Alfin-like proteins (ALs) form a plant-specific transcription factor (TF) gene family involved in the regulation of plant growth and development, and abiotic stress response. In this study, 30 ALs were identified in Brassica napus ecotype 'Zhongshuang 11' genome (BnaALs), and unevenly distributed on 15 chromosomes. Structural characteristic analysis showed that all of the BnaALs contained two highly conserved domains: the N terminal DUF3594 domain and the C-terminal PHD-finger domain. The BnaALs were classified into four groups (Group I-IV), supported by conserved intron-exon and protein motif structures in each group. The allopolyploid event between B. oleracea and B. rapa ancestors and the small-scale duplication events in B. napus both contributed to the large BnaALs expansion. The promoter regions of BnaALs contained multiple abiotic stress cis-elements. The BnaALs in I-IV groups were mainly expressed in cotyledon, petal, root, silique, and seed tissues, and the duplicated gene pairs shared highly similar expression patterns. RNA-seq and RT-qPCR analysis showed that BnaALs were obviously induced by low nitrogen (LN) and low phosphorus (LP) treatments in roots. Overexpressing BnaAL02 and BnaAL28 in Arabidopsis demonstrated their functions in response to LN and LP stresses. BnaAL28 enhanced primary roots' (PRs) length and lateral roots' (LRs) number under LP and LN conditions, where BnaAL02 can inhibit LR numbers under the two conditions. They can promote root hair (RH) elongation under LP conditions; however, they suppressed RH elongation under LN conditions. Our result provides new insight into the functional dissection of this family in response to nutrient stresses in plants.}, } @article {pmid39273694, year = {2024}, author = {Evangelisti, C and Ramadan, S and Orlacchio, A and Panza, E}, title = {Experimental Cell Models for Investigating Neurodegenerative Diseases.}, journal = {International journal of molecular sciences}, volume = {25}, number = {17}, pages = {}, pmid = {39273694}, issn = {1422-0067}, mesh = {Humans ; *Neurodegenerative Diseases/therapy/pathology/metabolism ; Animals ; *Induced Pluripotent Stem Cells/cytology/metabolism ; *Organoids/pathology ; Models, Biological ; }, abstract = {Experimental models play a pivotal role in biomedical research, facilitating the understanding of disease mechanisms and the development of novel therapeutics. This is particularly true for neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and motor neuron disease, which present complex challenges for research and therapy development. In this work, we review the recent literature about experimental models and motor neuron disease. We identified three main categories of models that are highly studied by scientists. In fact, experimental models for investigating these diseases encompass a variety of approaches, including modeling the patient's cell culture, patient-derived induced pluripotent stem cells, and organoids. Each model offers unique advantages and limitations, providing researchers with a range of tools to address complex biological questions. Here, we discuss the characteristics, applications, and recent advancements in terms of each model system, highlighting their contributions to advancing biomedical knowledge and translational research.}, } @article {pmid39273435, year = {2024}, author = {Di Chiano, M and Sallustio, F and Fiocco, D and Rocchetti, MT and Spano, G and Pontrelli, P and Moschetta, A and Gesualdo, L and Gadaleta, RM and Gallone, A}, title = {Psychobiotic Properties of Lactiplantibacillus plantarum in Neurodegenerative Diseases.}, journal = {International journal of molecular sciences}, volume = {25}, number = {17}, pages = {}, pmid = {39273435}, issn = {1422-0067}, support = {1062//PON "RICERCA E INNOVAZIONE" 2014-2020-Innovazione/ ; Call for tender No. 341 of 15 March 2022 of Italian Ministry of University and Research funded by the European Union - Next Generation EU//National Recovery and Resilience Plan (NRRP)/ ; Concession Decree No. 1550 of 11 October 2022 adopted by the Italian Ministry of University and Research, CUP D93C22000890001//Italian Ministry of University and Research, CUP D93C22000890001/ ; Codice progetto n. 2022H9MPZ5//MIUR- PRIN Progetti di Ricerca di Rilevante Interesse Nazionale 2022/ ; Id. 23239//AIRC IG 2019/ ; Call for tender No. 3138 of 16/12/2021 of Italian Ministry of University and Research funded by the European Union//National Recovery and Resilience Plan (NRRP)/ ; Project code: CN00000041, CUP H93C22000430007//NextGenerationEU/ ; PNRR-MR1-2022-12376395//European Union - Next Generation EU - PNRR M6C2/ ; "POFACS" - ARS01_00640 -", D.D. 1211/2020 and 1104/2021//Italian Ministry of University and Research (MIUR)/ ; PRA-HE 2021//University of Foggia/ ; }, mesh = {Humans ; *Neurodegenerative Diseases/microbiology/metabolism ; *Gastrointestinal Microbiome ; *Probiotics/therapeutic use ; Dysbiosis/microbiology ; Brain-Gut Axis ; Animals ; }, abstract = {Neurodegenerative disorders are the main cause of cognitive and physical disabilities, affect millions of people worldwide, and their incidence is on the rise. Emerging evidence pinpoints a disturbance of the communication of the gut-brain axis, and in particular to gut microbial dysbiosis, as one of the contributors to the pathogenesis of these diseases. In fact, dysbiosis has been associated with neuro-inflammatory processes, hyperactivation of the neuronal immune system, impaired cognitive functions, aging, depression, sleeping disorders, and anxiety. With the rapid advance in metagenomics, metabolomics, and big data analysis, together with a multidisciplinary approach, a new horizon has just emerged in the fields of translational neurodegenerative disease. In fact, recent studies focusing on taxonomic profiling and leaky gut in the pathogenesis of neurodegenerative disorders are not only shedding light on an overlooked field but are also creating opportunities for biomarker discovery and development of new therapeutic and adjuvant strategies to treat these disorders. Lactiplantibacillus plantarum (LBP) strains are emerging as promising psychobiotics for the treatment of these diseases. In fact, LBP strains are able to promote eubiosis, increase the enrichment of bacteria producing beneficial metabolites such as short-chain fatty acids, boost the production of neurotransmitters, and support the homeostasis of the gut-brain axis. In this review, we summarize the current knowledge on the role of the gut microbiota in the pathogenesis of neurodegenerative disorders with a particular focus on the benefits of LBP strains in Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, autism, anxiety, and depression.}, } @article {pmid39273079, year = {2024}, author = {Lundt, S and Ding, S}, title = {Potential Therapeutic Interventions Targeting NAD[+] Metabolism for ALS.}, journal = {Cells}, volume = {13}, number = {17}, pages = {}, pmid = {39273079}, issn = {2073-4409}, support = {R01NS069726/NS/NINDS NIH HHS/United States ; R01 NS123023/NS/NINDS NIH HHS/United States ; R21 AG080715/AG/NIA NIH HHS/United States ; R01 NS069726/NS/NINDS NIH HHS/United States ; R21AG080715/AG/NIA NIH HHS/United States ; R01NS123023/NS/NINDS NIH HHS/United States ; }, mesh = {*Amyotrophic Lateral Sclerosis/metabolism/drug therapy ; *NAD/metabolism ; Humans ; Animals ; Disease Models, Animal ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease affecting both upper and lower motor neurons. While there have been many potential factors implicated for ALS development, such as oxidative stress and mitochondrial dysfunction, no exact mechanism has been determined at this time. Nicotinamide adenine dinucleotide (NAD[+]) is one of the most abundant metabolites in mammalian cells and is crucial for a broad range of cellular functions from DNA repair to energy homeostasis. NAD[+] can be synthesized from three different intracellular pathways, but it is the NAD[+] salvage pathway that generates the largest proportion of NAD[+]. Impaired NAD[+] homeostasis has been connected to aging and neurodegenerative disease-related dysfunctions. In ALS mice, NAD[+] homeostasis is potentially disrupted prior to the appearance of physical symptoms and is significantly reduced in the nervous system at the end stage. Treatments targeting NAD[+] metabolism, either by administering NAD[+] precursor metabolites or small molecules that alter NAD[+]-dependent enzyme activity, have shown strong beneficial effects in ALS disease models. Here, we review the therapeutic interventions targeting NAD[+] metabolism for ALS and their effects on the most prominent pathological aspects of ALS in animal and cell models.}, } @article {pmid39271939, year = {2024}, author = {Yu, Y and Pang, D and Huang, J and Li, C and Cui, Y and Shang, H}, title = {Downregulation of Lnc-ABCA12-3 modulates UBQLN1 expression and protein homeostasis pathways in amyotrophic lateral sclerosis.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {21383}, pmid = {39271939}, issn = {2045-2322}, support = {2022NSFSC0750//The Sichuan Science and Technology Program/ ; 81871000//National Natural Science Foundation of China/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology ; Humans ; *RNA, Long Noncoding/genetics/metabolism ; *Autophagy-Related Proteins/genetics/metabolism ; *Down-Regulation ; *Adaptor Proteins, Signal Transducing/metabolism/genetics ; *Apoptosis/genetics ; Female ; Proteostasis ; Male ; Middle Aged ; Autophagy/genetics ; Oxidative Stress ; Gene Expression Regulation ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by motor neuron degeneration. Dysregulation of long non-coding RNAs (lncRNAs) has been implicated in ALS pathogenesis but their roles remain unclear. Previous studies found lnc-ABCA12-3 was downregulated in ALS patients. We aim to characterize the expression and function of lnc-ABCA12-3 in ALS and explore its mechanisms of action. Lnc-ABCA12-3 expression was analyzed in PBMCs from ALS patients and correlated with clinical outcomes. Effect of modulating lnc-ABCA12-3 expression was assessed in cell models using assays of apoptosis, protein homeostasis and pathway analysis. RNA pull-down and interaction studies were performed to identify lnc-ABCA12-3 binding partners. Lnc-ABCA12-3 was downregulated in ALS patients, correlating with faster progression and shorter survival. Overexpression of lnc-ABAC12-3 conferred protection against oxidative stress-induced apoptosis, while knockdown lnc-ABCA12-3 enhanced cell death. Lnc-ABCA12-3 maintained protein quality control pathways, including ubiquitination, autophagy and stress granule formation, by regulating the ubiquitin shuttle protein UBQLN1. This study identified lnc-ABCA12-3 as a novel regulatory lncRNA implicated in ALS pathogenesis by modulating cellular survival and stress responses through interactions with UBQLN1, influencing disease progression. Lnc-ABCA12-3 may influence ALS through regulating protein homeostasis pathways.}, } @article {pmid39271680, year = {2024}, author = {Shan, Y and Zhang, M and Tao, E and Wang, J and Wei, N and Lu, Y and Liu, Q and Hao, K and Zhou, F and Wang, G}, title = {Pharmacokinetic characteristics of mesenchymal stem cells in translational challenges.}, journal = {Signal transduction and targeted therapy}, volume = {9}, number = {1}, pages = {242}, pmid = {39271680}, issn = {2059-3635}, support = {82104184//National Natural Science Foundation of China (National Science Foundation of China)/ ; 82373949//National Natural Science Foundation of China (National Science Foundation of China)/ ; 82073928//National Natural Science Foundation of China (National Science Foundation of China)/ ; }, mesh = {Humans ; *Mesenchymal Stem Cells/metabolism/cytology ; *Mesenchymal Stem Cell Transplantation ; Graft vs Host Disease/therapy ; Translational Research, Biomedical ; Amyotrophic Lateral Sclerosis/therapy ; }, abstract = {Over the past two decades, mesenchymal stem/stromal cell (MSC) therapy has made substantial strides, transitioning from experimental clinical applications to commercial products. MSC therapies hold considerable promise for treating refractory and critical conditions such as acute graft-versus-host disease, amyotrophic lateral sclerosis, and acute respiratory distress syndrome. Despite recent successes in clinical and commercial applications, MSC therapy still faces challenges when used as a commercial product. Current detection methods have limitations, leaving the dynamic biodistribution, persistence in injured tissues, and ultimate fate of MSCs in patients unclear. Clarifying the relationship between the pharmacokinetic characteristics of MSCs and their therapeutic effects is crucial for patient stratification and the formulation of precise therapeutic regimens. Moreover, the development of advanced imaging and tracking technologies is essential to address these clinical challenges. This review provides a comprehensive analysis of the kinetic properties, key regulatory molecules, different fates, and detection methods relevant to MSCs and discusses concerns in evaluating MSC druggability from the perspective of integrating pharmacokinetics and efficacy. A better understanding of these challenges could improve MSC clinical efficacy and speed up the introduction of MSC therapy products to the market.}, } @article {pmid39271636, year = {2025}, author = {Wang, Y and Ju, R and Jiang, J and Mao, L and Li, X and Deng, M}, title = {Concomitant presence of a novel ARPP21 variant and CNVs in Chinese familial amyotrophic lateral sclerosis-frontotemporal dementia patients.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {46}, number = {1}, pages = {195-205}, pmid = {39271636}, issn = {1590-3478}, support = {No. 82273915//National Natural Science Foundation of China/ ; }, mesh = {Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; *Amyotrophic Lateral Sclerosis/genetics ; China ; *DNA Copy Number Variations/genetics ; East Asian People/genetics ; *Frontotemporal Dementia/genetics ; Pedigree ; Profilins/genetics ; Whole Genome Sequencing ; *Phosphoproteins/genetics ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder marked by the degeneration of motor neurons and progressive muscle weakness. Heredity plays an important part in the pathogenesis of ALS. Recently, with the emergence of the oligogenic pathogenic mechanism in ALS and the ongoing discovery of new mutated genes and genomic variants, there is an emerging need for larger-scale and more comprehensive genetic screenings in higher resolution. In this study, we performed whole-genome sequencing (WGS) on 34 familial ALS probands lacking the most common disease-causing mutations to explore the genetic landscape of Chinese ALS patients further. Among them, we identified a novel ARPP21 c.1231G > A (p.Glu411Lys) variant and two copy number variations (CNVs) affecting the PFN1 and RBCK1 genes in a patient with ALS-frontotemporal dementia (FTD). This marks the first report of an ARPP21 variant in Chinese ALS-FTD patients, providing fresh evidence for the association between ARPP21 and ALS. Our findings also underscore the potential role of CNVs in ALS-FTD, suggesting that the cumulative effect of multiple rare variants may contribute to disease onset. Furthermore, compared to the averages in our cohort and the reported Chinese ALS population, this patient displayed a shorter survival time and more rapid disease progression, suggesting the possibility of an oligogenic mechanism in disease pathogenesis. Further research will contribute to a deeper understanding of the rare mutations and their interactions, thus advancing our understanding of the genetic mechanisms underlying ALS and ALS-FTD.}, } @article {pmid39270726, year = {2024}, author = {Roos, AK and Stenvall, E and Kockum, ES and Grönlund, KÅ and Alstermark, H and Wuolikainen, A and Andersen, PM and Nordin, A and Forsberg, KME}, title = {Small striatal huntingtin inclusions in patients with motor neuron disease with reduced penetrance and intermediate HTT gene expansions.}, journal = {Human molecular genetics}, volume = {33}, number = {22}, pages = {1966-1974}, pmid = {39270726}, issn = {1460-2083}, support = {//Umea University/ ; Nos.FO 2022-0309//Swedish Brain Foundation/ ; 2012-3167//Swedish Research Council/ ; //Research and Development Unit/ ; JLL-980693//Region Jämtland Härjedalen/ ; 2012.0091//Knut and Alice Wallenberg Foundation/ ; //Neuroförbundet patient organization/ ; 2023.16//Ulla-Carin Lindquist Foundation/ ; RV-993493//Västerbotten County Council/ ; //King Gustaf V:s and Queen Victoria's Freemason's Foundation/ ; //Börje Salming ALS Foundation/ ; }, mesh = {Humans ; *Huntingtin Protein/genetics/metabolism ; *Penetrance ; Male ; Female ; *Motor Neuron Disease/genetics/pathology/metabolism ; Middle Aged ; Aged ; *C9orf72 Protein/genetics/metabolism ; *DNA Repeat Expansion/genetics ; Amyotrophic Lateral Sclerosis/genetics/pathology/metabolism ; Inclusion Bodies/metabolism/genetics/pathology ; Alleles ; Adult ; Huntington Disease/genetics/pathology/metabolism ; Cohort Studies ; Corpus Striatum/metabolism/pathology ; }, abstract = {Short tandem repeat expansions in the human genome are overrepresented in a variety of neurological disorders. It was recently shown that huntingtin (HTT) repeat expansions with full penetrance, i.e. 40 or more CAG repeats, which normally cause Huntington's disease (HD), are overrepresented in patients with amyotrophic lateral sclerosis (ALS). Whether patients carrying HTT repeat expansions with reduced penetrance, (36-39 CAG repeats), or alleles with intermediate penetrance, (27-35 CAG repeats), have an increased risk of ALS has not yet been investigated. Here, we examined the role of HTT repeat expansions in a motor neuron disease (MND) cohort, searched for expanded HTT alleles, and investigated correlations with phenotype and neuropathology. MND patients harboring C9ORF72 hexanucleotide repeat expansions (HREs) were included, to investigate whether HTT repeat expansions were more common in this group. We found a high prevalence of intermediate (range 5.63%-6.61%) and reduced penetrance (range 0.57%-0.66%) HTT gene expansions in this cohort compared to other populations of European ancestry, but no differences between the MND cohort and the control cohort were observed, regardless of C9ORF72HRE status. Upon autopsy of three patients with intermediate or reduced penetrance HTT alleles, huntingtin inclusions were observed in the caudate nucleus and frontal lobe, but no significant somatic mosaicism was detected in different parts of the nervous system. Thus, we demonstrate, for the first time, huntingtin inclusions in individuals with MND and intermediate and reduced penetrance HTT repeat expansions but more clinicopathological investigations are needed to further understand the impact of HTT gene expansion-related pleiotropy.}, } @article {pmid39270623, year = {2024}, author = {Benatar, M and Macklin, EA and Malaspina, A and Rogers, ML and Hornstein, E and Lombardi, V and Renfrey, D and Shepheard, S and Magen, I and Cohen, Y and Granit, V and Statland, JM and Heckmann, JM and Rademakers, R and McHutchison, CA and Petrucelli, L and McMillan, CT and Wuu, J and , }, title = {Prognostic clinical and biological markers for amyotrophic lateral sclerosis disease progression: validation and implications for clinical trial design and analysis.}, journal = {EBioMedicine}, volume = {108}, number = {}, pages = {105323}, pmid = {39270623}, issn = {2352-3964}, support = {R35 NS097273/NS/NINDS NIH HHS/United States ; U01 NS107027/NS/NINDS NIH HHS/United States ; }, mesh = {Aged ; Female ; Humans ; Male ; Middle Aged ; *Amyotrophic Lateral Sclerosis/blood/diagnosis/mortality ; *Biomarkers/blood ; *Clinical Trials as Topic ; *Disease Progression ; Neurofilament Proteins/blood ; Prognosis ; Research Design ; Multicenter Studies as Topic ; }, abstract = {BACKGROUND: With increasing recognition of the value of incorporating prognostic markers into amyotrophic lateral sclerosis (ALS) trial design and analysis plans, there is a pressing need to understand which among the prevailing clinical and biochemical markers have real value, and how they can be optimally used.

METHODS: A subset of patients with ALS recruited through the multi-center Phenotype-Genotype-Biomarker study (clinicaltrials.gov: NCT02327845) was identified as "trial-like" based on meeting common trial eligibility criteria. Clinical phenotyping was performed by evaluators trained in relevant assessments. Serum neurofilament light (NfL) and phosphorylated neurofilament heavy (pNfH), urinary p75[ECD], plasma microRNA-181, and an array of biochemical and clinical measures were evaluated for their prognostic value. Associations with functional progression were estimated by random-slopes mixed models of ALS functional rating scale-revised (ALSFRS-R) score. Associations with survival were estimated by log-rank test and Cox proportional hazards regression. Potential sample size savings from adjusting for given biomarkers in a hypothetical trial were estimated.

FINDINGS: Baseline serum NfL is a powerful prognostic biomarker, predicting survival and ALSFRS-R rate of decline. Serum NfL <40 pg/mL and >100 pg/mL correspond to future ALSFRS-R slopes of ∼0.5 and ∼1.5 points/month, respectively. Serum NfL also adds value to the best available clinical predictors, encapsulated by the European Network to Cure ALS (ENCALS) predictor score. In models of functional decline, the addition of NfL yields ∼25% sample size saving above those achieved by inclusion of either clinical predictors or ENCALS score alone. The prognostic value of serum pNfH, urinary p75[ECD], and plasma miR-181ab is more limited.

INTERPRETATION: Among the multitude of biomarkers considered, only blood NfL adds value to the ENCALS prediction model and should be incorporated into analysis plans for all ongoing and future ALS trials. Defined thresholds of NfL might also be used in trial design, for enrichment or stratified randomisation, to improve trial efficiency.

FUNDING: NIH (U01-NS107027, U54-NS092091). ALSA (16-TACL-242).}, } @article {pmid39270519, year = {2024}, author = {Nishiyama, M and Koreki, A and Isose, S and Takeda, T and Ishikawa, A and Kokubun, S and Saito, Y and Ito, K and Arai, K and Takahashi, N and Motoda, Y and Kuwabara, S and Honda, K}, title = {Factors associated with psychological distress in patients with amyotrophic lateral sclerosis: A retrospective medical records study.}, journal = {Journal of psychosomatic research}, volume = {187}, number = {}, pages = {111915}, doi = {10.1016/j.jpsychores.2024.111915}, pmid = {39270519}, issn = {1879-1360}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/psychology/complications ; Male ; Female ; Middle Aged ; *Psychological Distress ; Aged ; Retrospective Studies ; Adult ; Depression/psychology ; Stress, Psychological/psychology ; Surveys and Questionnaires ; Risk Factors ; Sex Factors ; }, abstract = {OBJECTIVE: Although psychological distress is a prevalent issue among patients with amyotrophic lateral sclerosis (ALS) and can impact survival, the risk factors contributing to this distress remain insufficiently understood.

METHODS: Patients with ALS who completed the Profile of Mood States (POMS) between June 2017 and March 2022 were included. Participants with moderate to severe cognitive decline were excluded, resulting in the recruitment of 121 patients. The associations between POMS profiles and clinical characteristics were analyzed. Physical motor symptoms were evaluated using the Revised ALS Functional Rating Scale (ALSFRS-R) for objective measurement and the 40-item ALS Assessment Questionnaire (ALSAQ-40) for subjective assessment.

RESULTS: Our model, employing the ALSFRS-R, revealed significant factors associated with overall psychological distress, as assessed by the POMS, including upper limb symptoms, the presence of sleep apnea syndrome, older age at onset, and male sex, with an inverse association with tracheostomy. The POMS subscale scores revealed that anger and depression were significantly associated with upper limb symptoms. The second model, which employed subjective scales, yielded similar results, reinforcing the robustness of our findings. Moreover, subjective bulbar symptoms on the ALSAQ-40 were significantly associated with psychological distress, particularly in female patients.

CONCLUSION: This study identified the main clinical characteristics significantly associated with psychological distress in patients with ALS. Our findings may be useful in developing individualized psychological management strategies for these patients.}, } @article {pmid39269505, year = {2024}, author = {Denis, PA and Laranjeira, JAS and Martins, NF and Sambrano, JR}, title = {Codoped germanene with 3p and 4p elements elements.}, journal = {Journal of molecular modeling}, volume = {30}, number = {10}, pages = {331}, pmid = {39269505}, issn = {0948-5023}, abstract = {CONTEXT: The relentless need for new materials to be used in electronic devices has opened new research directions in materials science. One of them involves using two-dimensional materials, among which there is current interest in using germanene. The heteroatom doping of germanene has been proposed as a possible approach to fine-tuning its electronic properties. However, this procedure is complicated because locating the dopants with a specific arrangement is challenging, thus achieving reproducibility. To avoid this problem, we propose the codoping of germanene to understand if dopants prefer to be agglomerated as observed for graphene or if they prefer to adopt a random disposition. Herein, we employed first-principles calculations to study 21 codoped germanene systems with one 3p (Al, Si, P, and S) and one 4p (Ga, As, and Se) element. Our results indicate that in the cases of AlP, AlS, GaP, GaS, GaAs, and GaSe codoped germanene, the dopants show a tendency to be located in specific lattice positions. The ortho disposition of dopants is preferred for AlP, AlS, GaP and GaS codoped germanene and their 4p counterparts GaAs and GaSe codoped germanene, and the materials showed interesting electronic properties making them suitable to develop germanene-based electronic materials.

METHODS: We utilized the M06-L, HSE06 methods accompanied by the 6-31G* basis sets to perform periodic boundary conditions calculations as implemented in Gaussian 09. The unit cells were sampled employing 100 k-points for geometry optimizations and 2000 k-points for electronic properties The ultrafine grid was employed. Results were visualized employing Gaussview 5.0.1. In addition to this, we performed B3LYP-D3 periodic calculations as implemented in CRYSTAL17.}, } @article {pmid39268841, year = {2024}, author = {Xing, C and Luo, M and Sheng, Q and Zhu, Z and Yu, D and Huang, J and He, D and Zhang, M and Fan, W and Chen, D}, title = {Silk Fabric Functionalized by Nanosilver Enabling the Wearable Sensing for Biomechanics and Biomolecules.}, journal = {ACS applied materials & interfaces}, volume = {16}, number = {38}, pages = {51669-51678}, doi = {10.1021/acsami.4c10253}, pmid = {39268841}, issn = {1944-8252}, mesh = {*Wearable Electronic Devices ; *Silver/chemistry ; *Silk/chemistry ; Humans ; *Metal Nanoparticles/chemistry ; Biomechanical Phenomena ; Textiles ; Biosensing Techniques/instrumentation/methods ; Spectrum Analysis, Raman ; }, abstract = {Integrating biomechanical and biomolecular sensing mechanisms into wearable devices is a formidable challenge and key to acquiring personalized health management. To address this, we have developed an innovative multifunctional sensor enabled by plasma functionalized silk fabric, which possesses multimodal sensing capabilities for biomechanics and biomolecules. A seed-mediated in situ growth method was employed to coat silver nanoparticles (AgNPs) onto silk fibers, resulting in silk fibers functionalized with AgNPs (SFs@Ag) that exhibit both piezoresistive response and localized surface plasmon resonance effects. The SFs@Ag membrane enables accurate detection of mechanical pressure and specific biomolecules during wearable sensing, offering a versatile solution for comprehensive personalized health monitoring. Additionally, a machine learning algorithm has been established to specifically recognize muscle strain signals, potentially extending to the diagnosis and monitoring of neuromuscular disorders such as amyotrophic lateral sclerosis (ALS). Unlike electromyography, which detects large muscles in clinical medicine, sensing data for tiny muscles enhance our understanding of muscle coordination using the SFs@Ag sensor. This detection model provides feasibility for the early detection and prevention of neuromuscular diseases. Beyond muscle stress and strain sensing, biomolecular detection is a critical addition to achieving effective health management. In this study, we developed highly sensitive surface-enhanced Raman scattering (SERS) detection for wearable health monitoring. Finite-difference time-domain numerical simulations ware utilized to analyze the efficacy of the SFs@Ag sensor for wearable SERS sensing of biomolecules. Based on the specific SERS spectra, automatic extraction of signals of sweat molecules was also achieved. In summary, the SFs@Ag sensor bridges the gap between biomechanical and biomolecular sensing in wearable applications, providing significant value for personalized health management.}, } @article {pmid39268298, year = {2024}, author = {Contractor, RN and Shah, M and Manwell, W and Dempsey, KJ and Simhadri, P}, title = {Jean-Martin Charcot: Pioneer of Neurology.}, journal = {Cureus}, volume = {16}, number = {8}, pages = {e66762}, pmid = {39268298}, issn = {2168-8184}, abstract = {Jean-Martin Charcot, born on November 29, 1825, in Paris, France, is known as the father of neurology. During a time when neurology was not yet a recognized medical specialty, Charcot's pioneering contributions significantly advanced the field. Charcot's use of the anatomo-clinical method, which correlates clinical symptoms with anatomical findings, led to the discovery and characterization of numerous neurological conditions, including multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), Charcot's joint, and Charcot-Marie-Tooth (CMT) disease. His methodical approach to documenting clinical signs and conducting post-mortem examinations revolutionized neurological research and diagnosis, laying the groundwork for modern neurology. The anatomo-clinical methods continue to be a vital tool in neurological research and practice today. Charcot's work extended beyond clinical practice, influencing the study of neurology through his role as an educator and mentor to many, including Sigmund Freud. Despite some controversies and a reputation for being difficult to work with, Charcot's legacy endures, with his initial discoveries fostering greater awareness and the development of therapies for various neurological disorders.}, } @article {pmid39267142, year = {2024}, author = {Wang, YM and Yan, J and Williams, SK and Fairless, R and Bading, H}, title = {TwinF interface inhibitor FP802 prevents retinal ganglion cell loss in a mouse model of amyotrophic lateral sclerosis.}, journal = {Acta neuropathologica communications}, volume = {12}, number = {1}, pages = {149}, pmid = {39267142}, issn = {2051-5960}, support = {BA 1007/7-1//Deutsche Forschungsgemeinschaft/ ; FOR 2289//Deutsche Forschungsgemeinschaft/ ; Advanced Grant 233024//HORIZON EUROPE European Research Council/ ; }, mesh = {Animals ; *Amyotrophic Lateral Sclerosis/pathology/metabolism/drug therapy ; *Retinal Ganglion Cells/drug effects/pathology/metabolism ; *Disease Models, Animal ; *Mice, Transgenic ; Mice ; Electroretinography ; Mice, Inbred C57BL ; Neuroprotective Agents/pharmacology ; Brain-Derived Neurotrophic Factor/metabolism ; Humans ; Basic Helix-Loop-Helix Transcription Factors/metabolism ; }, abstract = {Motor neuron loss is well recognized in amyotrophic lateral sclerosis (ALS), but research on retinal ganglion cells (RGCs) is limited. Ocular symptoms are generally not considered classic ALS symptoms, although RGCs and spinal motor neurons share certain cell pathologies, including hallmark signs of glutamate neurotoxicity, which may be triggered by activation of extrasynaptic NMDA receptors (NMDARs). To explore potential novel strategies to prevent ALS-associated death of RGCs, we utilized inhibition of the TwinF interface, a new pharmacological principle that detoxifies extrasynaptic NMDARs by disrupting the NMDAR/TRPM4 death signaling complex. Using the ALS mouse model SOD1[G93A], we found that the small molecule TwinF interface inhibitor FP802 prevents the loss of RGCs, improves pattern electroretinogram (pERG) performance, increases the retinal expression of Bdnf, and restores the retinal expression of the immediate early genes, Inhibin beta A and Npas4. Thus, FP802 not only prevents, as recently described, death of spinal motor neurons in SOD1[G93A] mice, but it also mitigates ALS-associated retinal damage. TwinF interface inhibitors have great potential for alleviating neuro-ophthalmologic symptoms in ALS patients and offer a promising new avenue for therapeutic intervention.}, } @article {pmid39266192, year = {2024}, author = {Chiappini, FA and Pinto, L and Alcaraz, MR and Omidikia, N and Goicoechea, HC and Olivieri, AC}, title = {Multivariate curve resolution-alternating least-squares and second-order advantage in first-order calibration. A systematic characterisation for three-component analytical systems.}, journal = {Analytica chimica acta}, volume = {1328}, number = {}, pages = {343159}, doi = {10.1016/j.aca.2024.343159}, pmid = {39266192}, issn = {1873-4324}, abstract = {BACKGROUND: Recent interest has been focused on the application of multivariate curve resolution-alternating least-squares (MCR-ALS) to systems involving the measurement of first-order and non-bilinear second-order data. The latter pose important challenges to bilinear decomposition models, due to the phenomenon of rotational ambiguity in the solutions, even under the application of the full set of chemical constraints that is usually employed in MCR-ALS calibration.

RESULTS: After the analysis of several simulated and experimental datasets, important conclusions regarding the role of the selectivity patterns in the constituent spectra have been drawn concerning the achievement of the second-order advantage. Theoretical considerations based on the calculation of the areas of feasible solutions helped to support the observations regarding the predictive ability of MCR- ALS in the various datasets.

SIGNIFICANCE: The understanding of the impact of rotational ambiguity in obtaining the second-order advantage with both first-order and non-bilinear second-order data is of paramount importance in the future development of analytical protocols of complex samples.}, } @article {pmid39264833, year = {2024}, author = {Su, B and He, Z and Liu, J and Li, M and Huang, X}, title = {Mangiferin activates the nuclear factor erythroid 2-related factor pathway to protect SOD1-G93A induced NSC-34 motor neurons from oxidative stress and apoptosis.}, journal = {Journal of biochemical and molecular toxicology}, volume = {38}, number = {10}, pages = {e23849}, doi = {10.1002/jbt.23849}, pmid = {39264833}, issn = {1099-0461}, mesh = {*Xanthones/pharmacology ; *NF-E2-Related Factor 2/metabolism/genetics ; *Oxidative Stress/drug effects ; *Apoptosis/drug effects ; Mice ; Animals ; *Motor Neurons/metabolism/drug effects/pathology ; *Signal Transduction/drug effects ; Reactive Oxygen Species/metabolism ; Cell Line ; Amyotrophic Lateral Sclerosis/metabolism/drug therapy ; Humans ; NAD(P)H Dehydrogenase (Quinone)/metabolism/genetics ; }, abstract = {One of the main factors in the pathophysiology of amyotrophic lateral sclerosis is oxidative stress. Mangiferin (MF), a natural plant polyphenol, has anti-inflammatory and antioxidant effects. The aim of our study was to investigate the protective effects and mechanisms of MF in the hSOD1-G93A ALS cell model. Our result revealed that MF treatment reduced the generation of reactive oxygen species (ROS) and malondialdehyde (MDA), decreased oxidative damage, and reduced apoptosis. Additionally, it was observed that MF significantly increased the synthesis of the antioxidant genes hemeoxygenase-1 and NAD(P)H: quinone oxidoreductase 1, which are downstream of the Nrf2 signaling pathway, and increased the expression and activation of nuclear factor erythroid 2-related factor 2 (Nrf2). Nrf2 knockdown greatly promoted apoptosis, which was reversed by MF treatment. To summarize, MF promoted the Nrf2 pathway and scavenged MDA and ROS to protect the ALS cell model.}, } @article {pmid39264557, year = {2024}, author = {Grigoryev, PN and Gaptrakhmanova, GA and Plotnikova, AA and Zefirov, AL and Mukhamedyarov, MA}, title = {Endocytosis of Synaptic Vesicle in Motor Nerve Endings of FUS Transgenic Mice with a Model of Amyotrophic Lateral Sclerosis.}, journal = {Bulletin of experimental biology and medicine}, volume = {177}, number = {4}, pages = {449-453}, pmid = {39264557}, issn = {1573-8221}, mesh = {Animals ; Mice ; *Amyotrophic Lateral Sclerosis/genetics/pathology/metabolism/physiopathology ; Diaphragm/innervation/metabolism/physiopathology ; *Disease Models, Animal ; *Endocytosis/physiology ; Fluorescent Dyes/metabolism ; Imidazoles/pharmacology ; Mice, Transgenic ; *Motor Neurons/metabolism/pathology ; Nerve Endings/metabolism ; Pyridinium Compounds/metabolism ; Quaternary Ammonium Compounds/metabolism ; RNA-Binding Protein FUS/genetics/metabolism ; Synaptic Transmission/physiology/genetics ; *Synaptic Vesicles/metabolism ; }, abstract = {In experiments on the motor nerve endings of the diaphragm of transgenic FUS mice with a model of amyotrophic lateral sclerosis at the pre-symptomatic stage of the disease, the processes of transmitter release and endocytosis of synaptic vesicles were studied. In FUS mice, the intensity of transmitter release during high-frequency stimulation of the motor nerve (50 imp/sec) was lowered. At the same duration of stimulation, the loading of fluorescent dye FM1-43 was lower in FUS mice. However, at the time of stimulation, during which an equal number of quanta are released in wild-type and FUS mice, no differences in the intensity of dye loading were found. Thus, endocytosis is not the key factor in the mechanism of synaptic dysfunction in FUS mice at the pre-symptomatic stage.}, } @article {pmid39263607, year = {2024}, author = {He, D and He, X and Shen, D and Liu, L and Yang, X and Hao, M and Wang, Y and Li, Y and Liu, Q and Liu, M and Wang, J and Zhang, X and Cui, L}, title = {Loss-of-function variants in RNA binding motif protein X-linked induce neuronal defects contributing to amyotrophic lateral sclerosis pathogenesis.}, journal = {MedComm}, volume = {5}, number = {9}, pages = {e712}, pmid = {39263607}, issn = {2688-2663}, abstract = {Despite being one of the most prevalent RNA modifications, the role of N6-methyladenosine (m6A) in amyotrophic lateral sclerosis (ALS) remains ambiguous. In this investigation, we explore the contribution of genetic defects of m6A-related genes to ALS pathogenesis. We scrutinized the mutation landscape of m6A genes through a comprehensive analysis of whole-exome sequencing cohorts, encompassing 508 ALS patients and 1660 population-matched controls. Our findings reveal a noteworthy enrichment of RNA binding motif protein X-linked (RBMX) variants among ALS patients, with a significant correlation between pathogenic m6A variants and adverse clinical outcomes. Furthermore, Rbmx knockdown in NSC-34 cells overexpressing mutant TDP43[Q331K] results in cell death mediated by an augmented p53 response. Similarly, RBMX knockdown in ALS motor neurons derived from induced pluripotent stem cells (iPSCs) manifests morphological defects and activation of the p53 pathway. Transcriptional analysis using publicly available single-cell sequencing data from the primary motor cortex indicates that RBMX-regulated genes selectively influence excitatory neurons and exhibit enrichment in ALS-implicated pathways. Through integrated analyses, our study underscores the emerging roles played by RBMX in ALS, suggesting a potential nexus between the disease and dysregulated m6A-mediated mRNA metabolism.}, } @article {pmid39262980, year = {2024}, author = {Joshi, R and Goswami, D and Saha, P and Hole, A and Mandhare, P and Wadke, R and Murthy, PR and Borgohain, S and C, MK and Kapoor, S}, title = {Serum Raman spectroscopy: Unearthing the snapshot of distinct metabolic profile in patients with congenital heart defects (CHDs).}, journal = {Heliyon}, volume = {10}, number = {16}, pages = {e34575}, pmid = {39262980}, issn = {2405-8440}, abstract = {In the present study, efficacy of minimally-invasive serum Raman spectroscopy (SRS) in stratification of congenital heart diseases was explored. Blood was collected from 62 subjects [42 congenital heart defect (CHD) patients (19 with atrial septal defect, 13 with ventricular septal defect and 10 with tetralogy of fallot) and 20 controls], and serum separated. Raman spectra of sera were recorded, pre-processed and subjected to spectral and multivariate analyses. Multivariate curve resolution-alternating least squares (MCR-ALS) analyses indicated alterations in lipid and protein levels between the study groups. Principal Component Analysis (PCA) and Principal Component based Linear Discriminant Analysis (PC-LDA), cross-validated with Leave-one-out cross validation (LOOCV), were employed to study stratification between the different groups. CHD could be classified from controls with 76 % efficiency. The different CHD subtypes could be distinguished with efficiencies as high as ∼90 %. To the best of our knowledge, differentiation between controls and CHDs as well as the stratification between controls and CHDs subtypes was for the first time successfully accomplished by serum-based Raman spectroscopy.}, } @article {pmid39261725, year = {2024}, author = {Abe, P and Lavalley, A and Morassut, I and Santinha, AJ and Roig-Puiggros, S and Javed, A and Klingler, E and Baumann, N and Prados, J and Platt, RJ and Jabaudon, D}, title = {Molecular programs guiding arealization of descending cortical pathways.}, journal = {Nature}, volume = {634}, number = {8034}, pages = {644-651}, pmid = {39261725}, issn = {1476-4687}, mesh = {Animals ; Female ; Male ; Mice ; Axons/metabolism ; Gene Expression Regulation, Developmental ; Motor Cortex/cytology/metabolism ; *Neocortex/anatomy & histology/cytology/metabolism ; *Neural Pathways ; *Neurons/metabolism/cytology ; Single-Cell Gene Expression Analysis ; Transcription Factors/metabolism ; }, abstract = {Layer 5 extratelencephalic (ET) neurons are present across neocortical areas and send axons to multiple subcortical targets[1-6]. Two cardinal subtypes exist[7,8]: (1) Slco2a1-expressing neurons (ETdist), which predominate in the motor cortex and project distally to the pons, medulla and spinal cord; and (2) Nprs1- or Hpgd-expressing neurons (ETprox), which predominate in the visual cortex and project more proximally to the pons and thalamus. An understanding of how area-specific ETdist and ETprox emerge during development is important because they are critical for fine motor skills and are susceptible to spinal cord injury and amyotrophic lateral sclerosis[9-12]. Here, using cross-areal mapping of axonal projections in the mouse neocortex, we identify the subtype-specific developmental dynamics of ET neurons. Whereas subsets of ETprox emerge by pruning of ETdist axons, others emerge de novo. We outline corresponding subtype-specific developmental transcriptional programs using single-nucleus sequencing. Leveraging these findings, we use postnatal in vivo knockdown of subtype-specific transcription factors to reprogram ET neuron connectivity towards more proximal targets. Together, these results show the functional transcriptional programs driving ET neuron diversity and uncover cell subtype-specific gene regulatory networks that can be manipulated to direct target specificity in motor corticofugal pathways.}, } @article {pmid39260590, year = {2024}, author = {Petel Légaré, V and Harji, ZA and Rampal, CJ and Antonicka, H and Gurberg, TJN and Persia, O and Rodríguez, EC and Shoubridge, EA and Armstrong, GAB}, title = {CHCHD10[P80L] knock-in zebrafish display a mild ALS-like phenotype.}, journal = {Experimental neurology}, volume = {382}, number = {}, pages = {114945}, doi = {10.1016/j.expneurol.2024.114945}, pmid = {39260590}, issn = {1090-2430}, mesh = {Animals ; *Zebrafish ; *Amyotrophic Lateral Sclerosis/genetics/pathology ; *Phenotype ; *Mitochondrial Proteins/genetics ; Zebrafish Proteins/genetics ; Motor Neurons/metabolism/pathology ; Gene Knock-In Techniques ; Animals, Genetically Modified ; Disease Models, Animal ; Neuromuscular Junction/pathology/genetics/metabolism ; }, abstract = {Mutations in the nuclear-encoded mitochondrial gene CHCHD10 have been observed in patients with a spectrum of diseases that include amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). To investigate the pathogenic nature of disease-associated variants of CHCHD10 we generated a zebrafish knock-in (KI) model expressing the orthologous ALS-associated CHCHD10[P80L] variant (zebrafish: Chchd10[P83L]). Larval chchd10[P83L/P83L] fish displayed reduced Chchd10 protein expression levels, motor impairment, reduced survival and abnormal neuromuscular junctions (NMJ). These deficits were not accompanied by changes in transcripts involved in the integrated stress response (ISR), phenocopying previous findings in our knockout (chchd10[-/-]). Adult, 11-month old chchd10[P83L/P83L] zebrafish, displayed smaller slow- and fast-twitch muscle cell cross-sectional areas compared to wild type zebrafish muscle cells. Motoneurons in the spinal cord of chchd10[P83L/P83L] zebrafish displayed similar cross-sectional areas to that of wild type motor neurons and significantly fewer motor neurons were observed when compared to chchd2[-/-] adult spinal cords. Bulk RNA sequencing using whole spinal cords of 7-month old fish revealed transcriptional changes associated with neuroinflammation, apoptosis, amino acid metabolism and mt-DNA inflammatory response in our chchd10[P83L/P83L] model. The findings presented here, suggest that the CHCHD10[P80L] variant confers an ALS-like phenotype when expressed in zebrafish.}, } @article {pmid39260416, year = {2024}, author = {Arseni, D and Nonaka, T and Jacobsen, MH and Murzin, AG and Cracco, L and Peak-Chew, SY and Garringer, HJ and Kawakami, I and Suzuki, H and Onaya, M and Saito, Y and Murayama, S and Geula, C and Vidal, R and Newell, KL and Mesulam, M and Ghetti, B and Hasegawa, M and Ryskeldi-Falcon, B}, title = {Heteromeric amyloid filaments of ANXA11 and TDP-43 in FTLD-TDP type C.}, journal = {Nature}, volume = {634}, number = {8034}, pages = {662-668}, pmid = {39260416}, issn = {1476-4687}, support = {R01 AG077444/AG/NIA NIH HHS/United States ; RF1 AG071177/AG/NIA NIH HHS/United States ; P30 AG072976/AG/NIA NIH HHS/United States ; U01 NS110437/NS/NINDS NIH HHS/United States ; R01 NS085770/NS/NINDS NIH HHS/United States ; P30 AG013854/AG/NIA NIH HHS/United States ; R01 AG056258/AG/NIA NIH HHS/United States ; R01 DC008552/DC/NIDCD NIH HHS/United States ; RF1 NS110437/NS/NINDS NIH HHS/United States ; P30 AG072977/AG/NIA NIH HHS/United States ; R01 AG080001/AG/NIA NIH HHS/United States ; R01 AG071177/AG/NIA NIH HHS/United States ; R01 NS137469/NS/NINDS NIH HHS/United States ; }, mesh = {Humans ; *Amyloid/chemistry/metabolism/ultrastructure ; *Annexins/chemistry/metabolism/ultrastructure ; Aphasia/complications/metabolism ; *Brain/metabolism/pathology/ultrastructure ; Cryoelectron Microscopy ; *DNA-Binding Proteins/chemistry/metabolism/ultrastructure ; *Frontotemporal Dementia/classification/complications/metabolism ; Models, Molecular ; Protein Multimerization ; }, abstract = {Neurodegenerative diseases are characterized by the abnormal filamentous assembly of specific proteins in the central nervous system[1]. Human genetic studies have established a causal role for protein assembly in neurodegeneration[2]. However, the underlying molecular mechanisms remain largely unknown, which is limiting progress in developing clinical tools for these diseases. Recent advances in cryo-electron microscopy have enabled the structures of the protein filaments to be determined from the brains of patients[1]. All neurodegenerative diseases studied to date have been characterized by the self-assembly of proteins in homomeric amyloid filaments, including that of TAR DNA-binding protein 43 (TDP-43) in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-TDP) types A and B[3,4]. Here we used cryo-electron microscopy to determine filament structures from the brains of individuals with FTLD-TDP type C, one of the most common forms of sporadic FTLD-TDP. Unexpectedly, the structures revealed that a second protein, annexin A11 (ANXA11), co-assembles with TDP-43 in heteromeric amyloid filaments. The ordered filament fold is formed by TDP-43 residues G282/G284-N345 and ANXA11 residues L39-Y74 from their respective low-complexity domains. Regions of TDP-43 and ANXA11 that were previously implicated in protein-protein interactions form an extensive hydrophobic interface at the centre of the filament fold. Immunoblots of the filaments revealed that the majority of ANXA11 exists as an approximately 22 kDa N-terminal fragment lacking the annexin core domain. Immunohistochemistry of brain sections showed the colocalization of ANXA11 and TDP-43 in inclusions, redefining the histopathology of FTLD-TDP type C. This work establishes a central role for ANXA11 in FTLD-TDP type C. The unprecedented formation of heteromeric amyloid filaments in the human brain revises our understanding of amyloid assembly and may be of significance for the pathogenesis of neurodegenerative diseases.}, } @article {pmid39260140, year = {2024}, author = {Emori, S and Kume, K and Nakayama, Y and Ito, H and Kawakami, H}, title = {C9orf72 repeat expansions in Wakayama: One potential cause of amyotrophic lateral sclerosis in the Kii Peninsula, Japan.}, journal = {Journal of the neurological sciences}, volume = {466}, number = {}, pages = {123209}, doi = {10.1016/j.jns.2024.123209}, pmid = {39260140}, issn = {1878-5883}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/epidemiology ; *C9orf72 Protein/genetics ; Japan/epidemiology ; Male ; Female ; *DNA Repeat Expansion/genetics ; Middle Aged ; Aged ; Proteins/genetics ; Adult ; Aged, 80 and over ; Genetic Predisposition to Disease/genetics ; Haplotypes ; }, abstract = {A cluster of cases of amyotrophic lateral sclerosis (ALS) exists in the southern part of the Kii Peninsula in Japan. Although both genetic and environmental factors are thought to be causative, the critical cause of this cluster has not been identified. C9orf72 is the most common genetic factor in both familial and sporadic C9orf72-related ALS in people of European ancestry, but it is rare among Japanese populations. However, a previous report revealed that the frequency of C9orf72-related ALS was significantly higher in the cluster area. We evaluated the proportion of C9orf72 hexanucleotide repeat expansions in 99 cases of ALS diagnosed in Wakayama Prefecture, including the cluster area, by using repeat-primed polymerase chain reaction and fluorescence fragment length analysis. We found that 2 of the 99 patients (0 % of those with familial ALS and 2.4 % of those with sporadic ALS) had hexanucleotide repeat expansions in C9orf72, and long-read sequencing revealed that these expansions were causative. No expansions were observed among 90 patients with Parkinson's disease or among 90 healthy controls. Haplotype analysis with long-read sequencing data revealed that the two patients with repeat expansions shared the common haplotype with that previously reported in Finnish patients with C9orf72-related ALS, which suggests a founder effect. C9orf72 was thought to be a rare causative gene in Japan, but this study revealed that it may be relatively common in Wakayama Prefecture.}, } @article {pmid39259763, year = {2024}, author = {Caredio, D and Koderman, M and Frontzek, KJ and Sorce, S and Nuvolone, M and Bremer, J and Mariutti, G and Schwarz, P and Madrigal, L and Mitrovic, M and Sellitto, S and Streichenberger, N and Scheckel, C and Aguzzi, A}, title = {Prion diseases disrupt glutamate/glutamine metabolism in skeletal muscle.}, journal = {PLoS pathogens}, volume = {20}, number = {9}, pages = {e1012552}, pmid = {39259763}, issn = {1553-7374}, mesh = {Animals ; *Muscle, Skeletal/metabolism/pathology ; *Glutamine/metabolism ; *Glutamic Acid/metabolism ; Mice ; *Prion Diseases/metabolism/genetics ; Humans ; Glutamate-Ammonia Ligase/metabolism ; Creutzfeldt-Jakob Syndrome/metabolism/pathology/genetics ; Female ; Mice, Inbred C57BL ; }, abstract = {In prion diseases (PrDs), aggregates of misfolded prion protein (PrPSc) accumulate not only in the brain but also in extraneural organs. This raises the question whether prion-specific pathologies arise also extraneurally. Here we sequenced mRNA transcripts in skeletal muscle, spleen and blood of prion-inoculated mice at eight timepoints during disease progression. We detected gene-expression changes in all three organs, with skeletal muscle showing the most consistent alterations. The glutamate-ammonia ligase (GLUL) gene exhibited uniform upregulation in skeletal muscles of mice infected with three distinct scrapie prion strains (RML, ME7, and 22L) and in victims of human sporadic Creutzfeldt-Jakob disease. GLUL dysregulation was accompanied by changes in glutamate/glutamine metabolism, leading to reduced glutamate levels in skeletal muscle. None of these changes were observed in skeletal muscle of humans with amyotrophic lateral sclerosis, Alzheimer's disease, or dementia with Lewy bodies, suggesting that they are specific to prion diseases. These findings reveal an unexpected metabolic dimension of prion infections and point to a potential role for GLUL dysregulation in the glutamate/glutamine metabolism in prion-affected skeletal muscle.}, } @article {pmid39258797, year = {2024}, author = {Coppedè, F}, title = {DNA methylation in amyotrophic lateral sclerosis: where do we stand and what is next?.}, journal = {Epigenomics}, volume = {16}, number = {17}, pages = {1185-1196}, pmid = {39258797}, issn = {1750-192X}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics ; *DNA Methylation ; Epigenesis, Genetic ; }, abstract = {Genes involved in immune response, inflammation and metabolism are among those most likely affected by changes in DNA methylation (DNAm) and expression levels in amyotrophic lateral sclerosis (ALS) tissues. Unfortunately, it is still largely unclear whether any of these changes precede the onset of disease symptoms or whether most of them are the result of the muscular and metabolic changes that follow symptoms onset. In this article the author discusses the strengths and limitations of the available studies of DNAm in ALS and provides some suggestions on what, in his opinion, could be done in the near future for a better understanding of the DNAm changes occurring in ALS, their link with environmental exposures and their potential clinical utility.}, } @article {pmid39258740, year = {2025}, author = {O'Connell, C and Kavanaugh, MS and Cummings, C and Genge, A}, title = {How to break the news in amyotrophic lateral sclerosis/motor neuron disease: practical guidelines from experts.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {26}, number = {1-2}, pages = {5-14}, doi = {10.1080/21678421.2024.2397517}, pmid = {39258740}, issn = {2167-9223}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/psychology/therapy/diagnosis ; Quality of Life/psychology ; *Communication ; *Motor Neuron Disease/psychology ; *Practice Guidelines as Topic/standards ; }, abstract = {In amyotrophic lateral sclerosis/motor neuron disease (ALS/MND), it is necessary to communicate difficult news during the initial diagnosis and throughout the disease trajectory as the condition progresses. However, delivering difficult news to people with ALS/MND is an emotionally demanding task for healthcare and allied health professionals-one for which many feel ill-prepared because of limited training in this area. Ineffective communication of difficult news damages the patient-provider relationship and negatively impacts patient quality of life (QoL). To address this issue, we developed the A-L S-PIKES protocol based on available literature and our extensive clinical experience. It provides easy-to-follow, stepwise guidelines to effectively deliver difficult news to people with ALS/MND (PALS) that includes: Advance Preparation (preparing for the discussion logistically and emotionally); Location & Setting (creating a comfortable setting that fosters rapport); Patient's Perceptions (assessing PALS' understanding and perception of their condition); Invitation (seeking PALS' permission to share information); Knowledge (sharing information in a clear, understandable manner); Emotion/Empathy (addressing emotions with empathy and providing emotional support); and Strategy & Summary (summarizing the discussion and collaboratively developing a plan of action). A-L S-PIKES provides practical guidelines on how to prepare for and conduct these challenging conversations. It emphasizes effective communication tailored to the individual needs of PALS and their families, empathy, sensitivity, and support for PALS' emotional well-being and autonomy. The aim of A-L S-PIKES is to both enhance skills and confidence in delivering difficult news and to improve the QoL of PALS and their families. Future studies should systematically evaluate the feasibility and effectiveness of A-L S-PIKES to establish its utility in clinical practice.}, } @article {pmid39258714, year = {2024}, author = {Winroth, I and Börjesson, A and Andersen, PM and Karlsson, T}, title = {Cognitive deficits in ALS patients with SOD1 mutations.}, journal = {Journal of clinical and experimental neuropsychology}, volume = {46}, number = {7}, pages = {669-682}, doi = {10.1080/13803395.2024.2393366}, pmid = {39258714}, issn = {1744-411X}, mesh = {Humans ; Female ; Male ; *Amyotrophic Lateral Sclerosis/genetics/complications/physiopathology ; *Superoxide Dismutase-1/genetics ; Middle Aged ; *Mutation ; Aged ; *Neuropsychological Tests ; Cognitive Dysfunction/physiopathology/genetics/etiology ; Adult ; Memory, Short-Term/physiology ; C9orf72 Protein/genetics ; Bayes Theorem ; }, abstract = {OBJECTIVE: Cognitive decline is common in patients with amyotrophic lateral sclerosis (ALS), especially in carriers of the mutation C9ORF72HRE. However, cognitive impairment is poorly understood in carriers of mutations in other genes causing ALS. We performed a comprehensive neuropsychological testing in patients with mutations in the SOD1 (mSOD1) gene.

METHODS: We examined 5 cognitive domains in 48 symptomatic patients with either hereditary or sporadic ALS. These were compared with 37 matched controls.

RESULTS: Carriers of SOD1-mutations and sporadic ALS had circumscribed deficits, but in a pattern different from C9ORF72HRE. All groups had deficits in working memory, although mSOD1-carriers significantly outperform sporadic ALS and C9ORF72HRE in an attention-driven visuospatial task involving copying a complex figure. Carriers of the D90A-SOD1 mutation overall performed as well as or better than carriers of other SOD1-mutations, except complex working memory. Bayesian analyses suggest (with evidence of moderate strength) that tasks involving the language domain did not differ between controls, mSOD1 and sporadic ALS.

CONCLUSION: Distinct cognitive impairments are prevalent in different ALS-syndromes and vary in patients with different pathogenic SOD1 mutations. The type and degree of impairment differed depending on genotype and was significantly least pronounced in patients homozygous for the D90A SOD1 mutation. The presence of cognitive deficits may influence optimal clinical management and intervention. We propose that cognitive assessment should be included in the routine examination of new patients suspected of ALS. Neuropsychological assessment is an under-recognized outcome parameter in clinical drug trials.}, } @article {pmid39258588, year = {2025}, author = {Walsh, S and Simmons, Z and Miyamoto, S and Geronimo, A}, title = {A nurse coaching intervention to improve support to individuals living with ALS.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {26}, number = {1-2}, pages = {22-28}, doi = {10.1080/21678421.2024.2399154}, pmid = {39258588}, issn = {2167-9223}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/psychology/nursing ; Male ; Female ; Middle Aged ; *Quality of Life/psychology ; *Mentoring/methods ; Aged ; Self Efficacy ; Motivational Interviewing/methods ; Caregivers/psychology ; Adult ; }, abstract = {OBJECTIVE: Health coaching may supplement the multidisciplinary ALS clinic model to facilitate patient-centered health behavior change. The aim of this study was to determine the effects of nurse health coaching (NHC) on the quality of life and self-efficacy of individuals living with ALS.

METHODS: Twenty-nine participants were randomized at 1:1 to the standard of care and coaching arms. All participants attended multidisciplinary ALS clinic visits quarterly, at which times they completed assessments of quality of life and self-efficacy. Those in the coaching arm participated in monthly coaching with a nurse coach over 12 months. The coaching sessions utilized motivational interviewing to identify personal goals along with barriers and solutions to achieve them. Linear mixed-effect models were used to quantify the effect of coaching on quality of life and self-efficacy outcomes. Thematic analysis was performed to summarize the participants' experiences with coaching.

RESULTS: Adherence to the coaching intervention was good. No effects of coaching were observed on the primary outcomes of quality of life and self-efficacy, although debriefed participants reported that they would recommend it to others. Patients and caregivers reflected on the impacts of coaching that extended beyond the pre-defined study outcomes and measures put in place to gauge effectiveness.

CONCLUSIONS: The elicited qualitative themes illustrating patient experience of coaching demonstrate the utility of nurse coaching as an important adjunct support to complement the multidisciplinary ALS clinic model.}, } @article {pmid39258586, year = {2025}, author = {Sommers-Spijkerman, M and Zwarts-Engelbert, A and Kruitwagen-Van Reenen, E and Van Eijk, RPA and Visser-Meily, JMA and Heijmans, E and Austin, J and Drossaert, C and Bohlmeijer, E and Beelen, A}, title = {Acceptability and potential benefit of a self-compassion intervention for people living with amyotrophic lateral sclerosis: a mixed methods pilot study.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {26}, number = {1-2}, pages = {29-39}, doi = {10.1080/21678421.2024.2400516}, pmid = {39258586}, issn = {2167-9223}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/psychology/therapy ; Pilot Projects ; Female ; Male ; Middle Aged ; *Empathy/physiology ; Aged ; *Adaptation, Psychological ; *Caregivers/psychology ; Adult ; Surveys and Questionnaires ; Psychological Distress ; *Self Concept ; }, abstract = {OBJECTIVE: This proof-of-concept study aimed to explore the acceptability and potential benefit of a self-guided online self-compassion intervention to aid resilient coping and reduce emotional distress among patients and caregivers living with ALS.

METHODS: A single-arm pilot study was conducted in 20 adults living with ALS either as a patient or as a caregiver. Acceptability was examined using questionnaires (n = 20) and semi-structured interviews (n = 9). Potential benefit was assessed as changes in self-compassion, self-criticism and emotional distress, determined using psychological questionnaires at 3 and 6 weeks. Questionnaires were analyzed using linear mixed-effects models and interview data using inductive thematic analysis.

RESULTS: Out of 20 participants who started the intervention, 16 completed the study (80%). The majority of study completers (12/16) were satisfied with the intervention, but the data suggest room for improvement in terms of personalization. Qualitative data revealed multiple psychological benefits of using the intervention, including self-kindness, emotional self-awareness and savoring. Although not statistically significant, quantitative data showed positive trends with increased self-compassion (mean difference: 2.07; 95% CI: -.5.76 - 1.63) and reduced self-criticism (mean difference: -2.62; 95% CI: -.1.97 - 7.23) and emotional distress (mean difference: -2.49; 95% CI: -.51 - 5.50) at week 6 compared to baseline.

CONCLUSIONS: The findings suggest that a self-compassion intervention is acceptable to people living with ALS, but its beneficial effects and the mechanisms involved have yet to be established in larger and more diverse samples, using controlled designs.}, } @article {pmid39257530, year = {2024}, author = {Baird, MC and Likhite, SB and Vetter, TA and Caporale, JR and Girard, HB and Roussel, FS and Howard, AE and Schwartz, MK and Reed, AR and Kaleem, A and Zhang, X and Meyer, KC}, title = {Combination AAV therapy with galectin-1 and SOD1 downregulation demonstrates superior therapeutic effect in a severe ALS mouse model.}, journal = {Molecular therapy. Methods & clinical development}, volume = {32}, number = {3}, pages = {101312}, pmid = {39257530}, issn = {2329-0501}, abstract = {Neuroinflammation is a miscreant in accelerating progression of many neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). However, treatments targeting neuroinflammation alone have led to disappointing results in clinical trials. Both neuronal and non-neuronal cell types have been implicated in the pathogenesis of ALS, and multiple studies have shown correction of each cell type has beneficial effects on disease outcome. Previously, we shown that AAV9-mediated superoxide dismutase 1 (SOD1) suppression in motor neurons and astrocytes significantly improves motor function and extends survival in ALS mouse models. Despite neuron and astrocyte correction, ALS mice still succumb to death with microgliosis observed in endpoint tissue. Therefore, we hypothesized that the optimal therapeutic approach will target and simultaneously correct motor neurons, astrocytes, and microglia. Here, we developed a novel approach to indirectly target microglia with galectin-1 (Gal1) and combined this with our previously established AAV9.SOD1.short hairpin RNA treatment. We show Gal1 conditioning of SOD1 [G93A] microglia decreases inflammatory markers and rescues motor neuron death in vitro. When paired with SOD1 downregulation, we found a synergistic effect of combination treatment in vivo and show a significant extension of survival of SOD1 [G93A] mice over SOD1 suppression alone. These results highlight the importance of targeting inflammatory microglia as a critical component in future therapeutic development.}, } @article {pmid39255192, year = {2024}, author = {Hwang, RD and Lu, Y and Tang, Q and Periz, G and Park, G and Li, X and Xiang, Q and Liu, Y and Zhang, T and Wang, J}, title = {DBT is a metabolic switch for maintenance of proteostasis under proteasomal impairment.}, journal = {eLife}, volume = {12}, number = {}, pages = {}, pmid = {39255192}, issn = {2050-084X}, support = {R01 NS128494/NS/NINDS NIH HHS/United States ; I01 BX002466/BX/BLRD VA/United States ; R01 NS074324/NS/NINDS NIH HHS/United States ; R01 NS110098/NS/NINDS NIH HHS/United States ; R01 NS089616/NS/NINDS NIH HHS/United States ; NS074324/NH/NIH HHS/United States ; NS089616/NH/NIH HHS/United States ; NS128494/NH/NIH HHS/United States ; NS110098/NH/NIH HHS/United States ; }, mesh = {Animals ; *Proteasome Endopeptidase Complex/metabolism ; *Proteostasis ; Humans ; Drosophila/metabolism ; Autophagy ; Amyotrophic Lateral Sclerosis/metabolism/genetics ; Neurons/metabolism ; Drosophila melanogaster/metabolism/genetics ; }, abstract = {Proteotoxic stress impairs cellular homeostasis and underlies the pathogenesis of many neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). The proteasomal and autophagic degradation of proteins are two major pathways for protein quality control in the cell. Here, we report a genome-wide CRISPR screen uncovering a major regulator of cytotoxicity resulting from the inhibition of the proteasome. Dihydrolipoamide branched chain transacylase E2 (DBT) was found to be a robust suppressor, the loss of which protects against proteasome inhibition-associated cell death through promoting clearance of ubiquitinated proteins. Loss of DBT altered the metabolic and energetic status of the cell and resulted in activation of autophagy in an AMP-activated protein kinase (AMPK)-dependent mechanism in the presence of proteasomal inhibition. Loss of DBT protected against proteotoxicity induced by ALS-linked mutant TDP-43 in Drosophila and mammalian neurons. DBT is upregulated in the tissues of ALS patients. These results demonstrate that DBT is a master switch in the metabolic control of protein quality control with implications in neurodegenerative diseases.}, } @article {pmid39255062, year = {2024}, author = {Germeys, C and Vandoorne, T and Davie, K and Poovathingal, S and Heeren, K and Vermeire, W and Nami, F and Moisse, M and Quaegebeur, A and Sierksma, A and Rué, L and Sicart, A and Eykens, C and De Cock, L and De Strooper, B and Carmeliet, P and Van Damme, P and De Bock, K and Van Den Bosch, L}, title = {Targeting EGLN2/PHD1 protects motor neurons and normalizes the astrocytic interferon response.}, journal = {Cell reports}, volume = {43}, number = {9}, pages = {114719}, doi = {10.1016/j.celrep.2024.114719}, pmid = {39255062}, issn = {2211-1247}, support = {/ERC_/European Research Council/International ; }, mesh = {Animals ; Humans ; Mice ; *Amyotrophic Lateral Sclerosis/drug therapy/genetics/metabolism/pathology ; *Astrocytes/metabolism ; Disease Models, Animal ; Hypoxia-Inducible Factor-Proline Dioxygenases/antagonists & inhibitors/genetics/metabolism ; Induced Pluripotent Stem Cells/metabolism ; Interferons/metabolism ; *Motor Neurons/metabolism ; *Zebrafish/metabolism ; }, abstract = {Neuroinflammation and dysregulated energy metabolism are linked to motor neuron degeneration in amyotrophic lateral sclerosis (ALS). The egl-9 family hypoxia-inducible factor (EGLN) enzymes, also known as prolyl hydroxylase domain (PHD) enzymes, are metabolic sensors regulating cellular inflammation and metabolism. Using an oligonucleotide-based and a genetic approach, we showed that the downregulation of Egln2 protected motor neurons and mitigated the ALS phenotype in two zebrafish models and a mouse model of ALS. Single-nucleus RNA sequencing of the murine spinal cord revealed that the loss of EGLN2 induced an astrocyte-specific downregulation of interferon-stimulated genes, mediated via the stimulator of interferon genes (STING) protein. In addition, we found that the genetic deletion of EGLN2 restored this interferon response in patient induced pluripotent stem cell (iPSC)-derived astrocytes, confirming the link between EGLN2 and astrocytic interferon signaling. In conclusion, we identified EGLN2 as a motor neuron protective target normalizing the astrocytic interferon-dependent inflammatory axis in vivo, as well as in patient-derived cells.}, } @article {pmid39254699, year = {2024}, author = {Maccabeo, A and Pateri, MI and Pili, F and Pilotto, S and Pierri, V and Muroni, A and Ercoli, T and Montisci, R and Marchetti, MF and Martis, A and Fazzini, L and Defazio, G and Puligheddu, M and Borghero, G}, title = {Takotsubo syndrome in a Sardinian amyotrophic lateral sclerosis cohort.}, journal = {Journal of neurology}, volume = {271}, number = {12}, pages = {7489-7493}, pmid = {39254699}, issn = {1432-1459}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/epidemiology/complications/physiopathology ; *Takotsubo Cardiomyopathy/physiopathology/epidemiology/etiology ; Female ; Italy/epidemiology ; Aged ; Middle Aged ; Retrospective Studies ; Cohort Studies ; Male ; }, abstract = {INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is known to be associated with varying degrees of autonomic and cardiovascular dysfunction. Recent case reports showed that ALS may be linked to Takotsubo syndrome (TTS). We assessed the frequency of TTS in an incident ALS cohort from Sardinia, Italy, and investigated the relationship of TTS with ALS course.

METHODS: We retrospectively examined a 10-year (2010-2019) incident cohort of ALS patients of Sardinian ancestry, reported TTS frequency and patients' clinical characteristics. Following, we checked for TTS among patients with ALS onset after 2019 and focused on the same features as for the incident cohort.

RESULTS: Our incident cohort included 344 ALS patients and 5 of them (1.45%) developed TTS. All were female and their median onset age was 71.5 years (IQR 62.75-77). Two patients had spinal and three bulbar onset, though all patients had bulbar involvement and were at an advanced stage of disease (ALSFRS ≤ 25, King's ≥ 3) at TTS diagnosis. We identified a potential TTS trigger in three patients (hospitalization for PEG placement, pneumonia). Among patients who had ALS onset after 2019, we identified a further TTS case and described it.

CONCLUSION: TTS is not a rare condition in ALS. Female sex, bulbar involvement, and later age of disease onset may be important risk factors for developing this cardiac condition and a physical or psychological trigger is often observed. Despite autonomic dysfunction in ALS has been already demonstrated, the precise physiopathological mechanism underlying TTS needs to be further clarified.}, } @article {pmid39254548, year = {2025}, author = {Zhang, M and Xiang, C and Niu, R and He, X and Luo, W and Liu, W and Gu, R}, title = {Liposomes as versatile agents for the management of traumatic and nontraumatic central nervous system disorders: drug stability, targeting efficiency, and safety.}, journal = {Neural regeneration research}, volume = {20}, number = {7}, pages = {1883-1899}, pmid = {39254548}, issn = {1673-5374}, abstract = {Various nanoparticle-based drug delivery systems for the treatment of neurological disorders have been widely studied. However, their inability to cross the blood-brain barrier hampers the clinical translation of these therapeutic strategies. Liposomes are nanoparticles composed of lipid bilayers, which can effectively encapsulate drugs and improve drug delivery across the blood-brain barrier and into brain tissue through their targeting and permeability. Therefore, they can potentially treat traumatic and nontraumatic central nervous system diseases. In this review, we outlined the common properties and preparation methods of liposomes, including thin-film hydration, reverse-phase evaporation, solvent injection techniques, detergent removal methods, and microfluidics techniques. Afterwards, we comprehensively discussed the current applications of liposomes in central nervous system diseases, such as Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, traumatic brain injury, spinal cord injury, and brain tumors. Most studies related to liposomes are still in the laboratory stage and have not yet entered clinical trials. Additionally, their application as drug delivery systems in clinical practice faces challenges such as drug stability, targeting efficiency, and safety. Therefore, we proposed development strategies related to liposomes to further promote their development in neurological disease research.}, } @article {pmid39254482, year = {2025}, author = {García-Parra, B and Guiu, JM and Povedano, M and Modamio, P}, title = {A scoping review of the role of managed entry agreements in upcoming drugs for amyotrophic lateral sclerosis: learning from the case of spinal muscular atrophy.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {26}, number = {1-2}, pages = {48-57}, doi = {10.1080/21678421.2024.2400522}, pmid = {39254482}, issn = {2167-9223}, mesh = {*Amyotrophic Lateral Sclerosis/drug therapy/economics ; Humans ; *Muscular Atrophy, Spinal/drug therapy/economics ; }, abstract = {INTRODUCTION: The therapeutic options for spinal muscular atrophy (SMA) are encouraging. However, there is currently no cure for amyotrophic lateral sclerosis (ALS). The clinical and economic uncertainty surrounding innovative treatments for rare neurodegenerative diseases makes it necessary to understand managed entry agreements (MEAs). The aim of this study was to review whether models of MEAs in SMA could be extrapolated to ALS.

METHODS: We performed a scoping review with information on MEAs on SMA in Web of Science (WOS), PubMed, Lyfegen Library, the National Institute for Health and Care Excellence (NICE), and the Canadian Agency for Drugs and Technologies in Health (CADTH).

RESULTS: We found 45 results in WOS and PubMed. After an initial survey, 10 were reviewed to assess eligibility, and three were selected. We obtained 44 results from Lyfegen Library, and three results each from NICE and CADTH.

CONCLUSION: The main objective of MEAs is to reduce uncertainty in the financing of drugs with a high budgetary impact and clinical concerns, as is the case with drugs for SMA and ALS. While the information available on MEAs in SMA is scarce, some conceptual models are publicly available. MEAs for long-term treatments for SMA could be used for the design of MEAs in ALS because of their similarities in economic and clinical uncertainty.}, } @article {pmid39253877, year = {2024}, author = {Thornburg-Suresh, EJC and Summers, DW}, title = {Microtubules, Membranes, and Movement: New Roles for Stathmin-2 in Axon Integrity.}, journal = {Journal of neuroscience research}, volume = {102}, number = {9}, pages = {e25382}, pmid = {39253877}, issn = {1097-4547}, support = {R01 NS126191/NS/NINDS NIH HHS/United States ; R01NS126191/NH/NIH HHS/United States ; }, mesh = {*Stathmin/metabolism ; *Microtubules/metabolism ; Humans ; *Axons/metabolism/physiology ; Animals ; Cell Membrane/metabolism ; Amyotrophic Lateral Sclerosis/metabolism/pathology ; }, abstract = {Neurons establish functional connections responsible for how we perceive and react to the world around us. Communication from a neuron to its target cell occurs through a long projection called an axon. Axon distances can exceed 1 m in length in humans and require a dynamic microtubule cytoskeleton for growth during development and maintenance in adulthood. Stathmins are microtubule-associated proteins that function as relays between kinase signaling and microtubule polymerization. In this review, we describe the prolific role of Stathmins in microtubule homeostasis with an emphasis on emerging roles for Stathmin-2 (Stmn2) in axon integrity and neurodegeneration. Stmn2 levels are altered in Amyotrophic Lateral Sclerosis and loss of Stmn2 provokes motor and sensory neuropathies. There is growing potential for employing Stmn2 as a disease biomarker or even a therapeutic target. Meeting this potential requires a mechanistic understanding of emerging complexity in Stmn2 function. In particular, Stmn2 palmitoylation has a surprising contribution to axon maintenance through undefined mechanisms linking membrane association, tubulin interaction, and axon transport. Exploring these connections will reveal new insight on neuronal cell biology and novel opportunities for disease intervention.}, } @article {pmid39253499, year = {2024}, author = {Thompson, EG and Spead, O and Akerman, SC and Curcio, C and Zaepfel, BL and Kent, ER and Philips, T and Vijayakumar, BG and Zacco, A and Zhou, W and Nagappan, G and Rothstein, JD}, title = {A robust evaluation of TDP-43, poly GP, cellular pathology and behavior in a AAV-C9ORF72 (G4C2)66 mouse model.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {39253499}, issn = {2692-8205}, support = {F32 NS120940/NS/NINDS NIH HHS/United States ; R35 NS132179/NS/NINDS NIH HHS/United States ; }, abstract = {The G4C2 hexanucleotide repeat expansion in C9ORF72 is the major genetic cause of both amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) (C9-ALS/FTD). Despite considerable efforts, the development of mouse models of C9-ALS/FTD useful for therapeutic development has proven challenging due to the intricate interplay of genetic and molecular factors underlying this neurodegenerative disorder, in addition to species differences. This study presents a robust investigation of the cellular pathophysiology and behavioral outcomes in a previously described AAV mouse model of C9-ALS expressing 66 G4C2 hexanucleotide repeats. Despite displaying key molecular ALS pathological markers including RNA foci, dipeptide repeat (DPR) protein aggregation, p62 positive stress granule formation as well as mild gliosis, the AAV-(G4C2)66 mouse model in this study exhibits negligible neuronal loss, no motor deficits, and functionally unimpaired TAR DNA-binding protein-43 (TDP-43). While our findings indicate and support that this is a robust and pharmacologically tractable model for investigating the molecular mechanisms and cellular consequences of (G4C2) repeat driven DPR pathology, it is not suitable for investigating the development of disease associated neurodegeneration, TDP-43 dysfunction, gliosis, and motor performance. Our findings underscore the complexity of ALS pathogenesis involving genetic mutations and protein dysregulation and highlight the need for more comprehensive model systems that reliably replicate the multifaceted cellular and behavioral aspects of C9-ALS.}, } @article {pmid39252332, year = {2024}, author = {Li, LS and Tong, Y and Yuan, C and Zhang, W}, title = {Evaluation of diagnostic value and Mendelian randomization study of appendicitis hub genes obtained by WGCNA analysis.}, journal = {Medicine}, volume = {103}, number = {36}, pages = {e39307}, doi = {10.1097/MD.0000000000039307}, pmid = {39252332}, issn = {1536-5964}, mesh = {Humans ; *Appendicitis/genetics/diagnosis ; *Mendelian Randomization Analysis ; Gene Expression Profiling/methods ; ROC Curve ; Gene Regulatory Networks ; Nomograms ; Gastrointestinal Microbiome/genetics ; }, abstract = {The timely and precise diagnosis of appendicitis was deemed essential. This study sought to examine the diagnostic significance of hub genes linked to appendicitis and to delve deeper into the pathophysiology of the condition. Differential gene expression analysis revealed distinct genes in the appendicitis group compared to other abdominal pain group, while weighted gene co-expression network analysis identified appendicitis-associated modules. Further analysis of common genes was conducted using Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analysis. The diagnostic efficiency of hub genes was explored through the use of nomograms and receiver operator characteristic curves. Additionally, immunoinfiltration analysis was performed to investigate the immune cell infiltration in both groups. The causal relationship between hub genes and appendicitis, as well as gut microbiota and appendicitis, was ultimately examined through Mendelian randomization. By conducting differential expression analysis and weighted gene co-expression network analysis, a total of 757 common genes were identified. Subsequent Kyoto Encyclopedia of Genes and Genomes and Gene Ontology enrichment analyses revealed that these common genes were primarily associated with positive regulation of cell adhesion, focal adhesion, protein serine kinase activity, and amyotrophic lateral sclerosis. Utilizing Cytoscape software, the top 10 genes with the highest degree of interaction were identified as RPS3A, RPSA, RPL5, RPL37A, RPS27L, FLT3LG, ARL6IP1, RPL32, MRPL3, and GSPT1. Evaluation using nomograms and receiver operator characteristic curves demonstrated the diagnostic value of these hub genes. Ultimately, a causal relationship between hub genes and appendicitis was not identified in our study. Nevertheless, our findings indicate that appendicitis is correlated with 9 gut microbiota. This study identified 5 hub genes, specifically HSP90AA1, RPL5, MYC, CD44, and RPS3A, which exhibit diagnostic significance of appendicitis. Furthermore, the elucidation of these hub genes aids in enhancing our comprehension of the molecular pathways implicated in the development of appendicitis.}, } @article {pmid39251386, year = {2024}, author = {Liddell, JR and Hilton, JBW and Wang, YJ and Billings, JL and Nikseresht, S and Kysenius, K and Fuller-Jackson, JP and Hare, DJ and Crouch, PJ}, title = {Decreased spinal cord motor neuron numbers in mice depleted of central nervous system copper.}, journal = {Metallomics : integrated biometal science}, volume = {16}, number = {9}, pages = {}, pmid = {39251386}, issn = {1756-591X}, support = {//National Health and Medical Research Council/ ; }, mesh = {Animals ; *Copper/metabolism ; *Motor Neurons/metabolism/pathology ; *Spinal Cord/metabolism/pathology ; Mice ; *Copper Transporter 1/metabolism ; *Amyotrophic Lateral Sclerosis/metabolism/pathology/genetics ; Central Nervous System/metabolism ; Mice, Transgenic ; Superoxide Dismutase-1/genetics/metabolism ; Disease Models, Animal ; }, abstract = {Disrupted copper availability in the central nervous system (CNS) is implicated as a significant feature of the neurodegenerative disease amyotrophic lateral sclerosis (ALS). Solute carrier family 31 member 1 (Slc31a1; Ctr1) governs copper uptake in mammalian cells and mutations affecting Slc31a1 are associated with severe neurological abnormalities. Here, we examined the impact of decreased CNS copper caused by ubiquitous heterozygosity for functional Slc31a1 on spinal cord motor neurons in Slc31a1+/- mice. Congruent with the CNS being relatively susceptible to disrupted copper availability, brain and spinal cord tissue from Slc31a1+/- mice contained significantly less copper than wild-type littermates, even though copper levels in other tissues were unaffected. Slc31a1+/- mice had less spinal cord α-motor neurons compared to wild-type littermates, but they did not develop any overt physical signs of motor impairment. By contrast, ALS model SOD1G37R mice had fewer α-motor neurons than control mice and exhibited clear signs of motor function impairment. With the expression of Slc31a1 notwithstanding, spinal cord expression of genes related to copper handling revealed only minor differences between Slc31a1+/- and wild-type mice. This contrasted with SOD1G37R mice where changes in the expression of copper handling genes were pronounced. Similarly, the expression of genes related to toxic glial activation was unchanged in spinal cords from Slc31a1+/- mice but highly upregulated in SOD1G37R mice. Together, results from the Slc31a1+/- mice and SOD1G37R mice indicate that although depleted CNS copper has a significant impact on spinal cord motor neuron numbers, the manifestation of overt ALS-like motor impairment requires additional factors.}, } @article {pmid39251203, year = {2025}, author = {Rolf, O and Blana, A and Hagedorn, P}, title = {Implantation of Reverse Shoulder Endoprothesis Using Navigation.}, journal = {Zeitschrift fur Orthopadie und Unfallchirurgie}, volume = {163}, number = {2}, pages = {176-180}, doi = {10.1055/a-2346-9916}, pmid = {39251203}, issn = {1864-6743}, abstract = {Die Implantation einer inversen Schulterendoprothese (TEP) stellt eine bewährte Methode zur Schmerzlinderung und Schulterfunktionsverbesserung dar. Die Ergebnisse variieren je nach Patientenalter, Krankheitsgrad und Erfahrung des Operateurs. Indikationen für eine inverse TEP sind vielfältig, von der Defektarthropathie bis hin zu Frakturen. Aktuelle Studien zeigen verbesserte Überlebensraten und reduzierte Komplikationen nach primärer Implantation. Die präoperative Planung mittels 3-D-CT oder MRT gilt als Goldstandard. Patientenspezifische Instrumente (PSI) wurden eingeführt, sind jedoch mit Kosten und Wartezeit verbunden. Die Navigation mit "Augmented Reality" (AR) bietet eine effizientere Alternative. Die intraoperative Übertragung der Planung auf den Patienten erfolgt über AR-Brillen und ermöglicht Echtzeitinformationen, wodurch der Chirurg den Blick vom Situs nicht abwenden muss. Dies optimiert den Workflow und bietet potenziell präzisere Implantationsresultate. Zusammenfassend bietet die Kombination von 3-D-Planung, Navigation und AR eine vielversprechende Methode für präzise und effiziente Implantationen von inversen Schulterendoprothesen. Allerdings steht der Nachweis verbesserter Standzeiten und Funktionsscores noch aus.}, } @article {pmid39251159, year = {2024}, author = {Liu, Y and Chen, H and Zhang, Z and Wang, J}, title = {Development of an integrated framework for dissecting source-oriented ecological and health risks of heavy metals in soils.}, journal = {Chemosphere}, volume = {364}, number = {}, pages = {143299}, doi = {10.1016/j.chemosphere.2024.143299}, pmid = {39251159}, issn = {1879-1298}, mesh = {*Metals, Heavy/analysis ; *Soil Pollutants/analysis ; Environmental Exposure/statistics & numerical data ; Risk Assessment ; Soil/chemistry ; }, abstract = {Heavy metals (HMs) in soils pose significant risks on ecosystem and human health. To design targeted regulatory measures for mitigating and controlling the risk, it is necessary to accurately identify the pollution sources and environmental risks of soil HMs, as well as to reveal the linkages between them. To date, yet systematic investigation aimed at deciphering the links between source apportionment of soil HMs and their associated environmental risks is still lacking. To fill the gap, an integrated framework has been developed in this study and applied for dissecting the source-sink relationship and source-oriented ecological and health risks of soil HMs in Shanxi, a province with rich coal resource, in which long-term coal mining activities in history has resulted in soil HMs pollution and unavoidably posed environmental risks. Two advanced receptor models, multivariate curve resolution alternating least squares based on maximum likelihood principal component analysis (MCR-ALS/MLPCA) and multilinear engine 2 (ME2), have been employed for apportioning the potential sources, and their apportionment results are jointly incorporated into a modified ecological risk index and a probabilistic health risk assessment model for identifying the source-oriented ecological and health risks posed by soil metals. The results show that the soils in study area have been polluted by HMs (i.e., Cd, Cr, Hg and As) to varying degrees. Industrial activities (35%-35.8%), agricultural activities (11.1%-20.5%), atmospheric deposition (10.5%-13%) and mix source (31.5%-42.6%) are apportioned as the main contributors of soil HMs in the area. The source-oriented ecological risk assessment suggests Hg has presented significant ecological risk and largely contributed by the sources from atmospheric deposition and industrial activities. The source-oriented health risk assessment shows the non-carcinogenic hazard level and carcinogenic risk posed by soil HMs in the study area are acceptable. Relatively, industrial activities and mix source have contributed more on the health risks.}, } @article {pmid39251025, year = {2025}, author = {Del Rosso, JQ and Zaenglein, A and Callender, V and Schlosser, B and Graber, E and Keri, J and Weiss, J}, title = {Response to Reynolds et al's "Guidelines of care for the management of acne vulgaris".}, journal = {Journal of the American Academy of Dermatology}, volume = {92}, number = {1}, pages = {e15}, doi = {10.1016/j.jaad.2024.07.1528}, pmid = {39251025}, issn = {1097-6787}, } @article {pmid39250425, year = {2025}, author = {Neuhaus, D and Rost, T and Haas, T and Wendebourg, MJ and Schulze, K and Schlaeger, R and Scheurer, E and Lenz, C}, title = {Comparative analysis of in situ and ex situ postmortem brain MRI: Evaluating volumetry, DTI, and relaxometry.}, journal = {Magnetic resonance in medicine}, volume = {93}, number = {1}, pages = {213-227}, doi = {10.1002/mrm.30264}, pmid = {39250425}, issn = {1522-2594}, support = {//Stiftung zur Foerderung der gastroenterologischen und der allgemeinen klinischen Forschung sowie der medizinischen Bildauswertung/ ; //Neuromuscular Research Association Basel/ ; }, mesh = {*Postmortem Imaging/methods ; *Brain/diagnostic imaging/drug effects/pathology ; *Diffusion Tensor Imaging/instrumentation/methods ; *Amyotrophic Lateral Sclerosis/diagnostic imaging/pathology ; Organ Size ; Tissue Fixation/methods ; *Formaldehyde/chemistry ; Anisotropy ; Humans ; Male ; Middle Aged ; Aged ; *Magnetic Resonance Imaging/instrumentation/methods ; }, abstract = {PURPOSE: To compare postmortem in situ with ex situ MRI parameters, including volumetry, diffusion tensor imaging (DTI), and relaxometry for assessing methodology-induced alterations, which is a crucial prerequisite when performing MRI biomarker validation.

METHODS: MRI whole-brain scans of five deceased patients with amyotrophic lateral sclerosis were performed at 3 T. In situ scans were conducted within 32 h after death (SD 18 h), and ex situ scans after brain extraction and 3 months of formalin fixation. The imaging protocol included MP2RAGE, DTI, and multi-contrast spin-echo and multi-echo gradient-echo sequences. Volumetry, fractional anisotropy, mean diffusivity, T1, T2, and T 2 * $$ {T} _2^{\ast } $$ have been assessed for specific brain regions.

RESULTS: When comparing ex situ to in situ values, the following results were obtained. Deep gray matter as well as the thalamus and the hippocampus showed a reduced volume. Fractional anisotropy was reduced in the cortex and the whole brain. Mean diffusivity was decreased in white matter and deep gray matter. T1 and T2 were reduced in all investigated structures, whereas T 2 * $$ {T} _2^{\ast } $$ was increased in the cortex.

CONCLUSION: The results of this study show that the volumes and MRI parameters of several brain regions are potentially affected by tissue extraction and subsequent formalin fixation, suggesting that methodological alterations are present in ex situ MRI. To avoid overlap of indistinguishable methodological and disease-related changes, we recommend performing in situ postmortem MRI as an additional intermediate step for in vivo MRI biomarker validation.}, } @article {pmid39249108, year = {2024}, author = {Jin, W and Boss, J and Bakulski, KM and Goutman, SA and Feldman, EL and Fritsche, LG and Mukherjee, B}, title = {Improving prediction models of amyotrophic lateral sclerosis (ALS) using polygenic, pre-existing conditions, and survey-based risk scores in the UK Biobank.}, journal = {Journal of neurology}, volume = {271}, number = {10}, pages = {6923-6934}, pmid = {39249108}, issn = {1432-1459}, support = {R01TS000344/CC/CDC HHS/United States ; 20-IIA-532//ALS Association/ ; K23 ES027221/ES/NIEHS NIH HHS/United States ; K23ES027221/NH/NIH HHS/United States ; R01NS127188/NH/NIH HHS/United States ; R01ES030049/NH/NIH HHS/United States ; R01 NS127188/NS/NINDS NIH HHS/United States ; R01 TS000344/TS/ATSDR CDC HHS/United States ; }, mesh = {*Amyotrophic Lateral Sclerosis/genetics/epidemiology/diagnosis ; Humans ; United Kingdom/epidemiology ; *Multifactorial Inheritance ; Male ; Female ; Middle Aged ; *Biological Specimen Banks ; Aged ; Genome-Wide Association Study ; Genetic Predisposition to Disease ; Adult ; Phenotype ; UK Biobank ; }, abstract = {BACKGROUND AND OBJECTIVES: Amyotrophic lateral sclerosis (ALS) causes profound impairments in neurological function, and a cure for this devastating disease remains elusive. This study aimed to identify pre-disposing genetic, phenotypic, and exposure-related factors for amyotrophic lateral sclerosis using multi-modal data and assess their joint predictive potential.

METHODS: Utilizing data from the UK (United Kingdom) Biobank, we analyzed an unrelated set of 292 ALS cases and 408,831 controls of European descent. Two polygenic risk scores (PRS) are constructed: "GWAS Hits PRS" and "PRS-CS," reflecting oligogenic and polygenic ALS risk profiles, respectively. Time-restricted phenome-wide association studies (PheWAS) were performed to identify pre-existing conditions increasing ALS risk, integrated into phenotypic risk scores (PheRS). A poly-exposure score ("PXS") captures the influence of environmental exposures measured through survey questionnaires. We evaluate the performance of these scores for predicting ALS incidence and stratifying risk, adjusting for baseline demographic covariates.

RESULTS: Both PRSs modestly predicted ALS diagnosis but with increased predictive power when combined (covariate-adjusted receiver operating characteristic [AAUC] = 0.584 [0.525, 0.639]). PheRS incorporated diagnoses 1 year before ALS onset (PheRS1) modestly discriminated cases from controls (AAUC = 0.515 [0.472, 0.564]). The "PXS" did not significantly predict ALS. However, a model incorporating PRSs and PheRS1 improved the prediction of ALS (AAUC = 0.604 [0.547, 0.667]), outperforming a model combining all risk scores. This combined risk score identified the top 10% of risk score distribution with a fourfold higher ALS risk (95% CI [2.04, 7.73]) versus those in the 40%-60% range.

DISCUSSION: By leveraging UK Biobank data, our study uncovers pre-disposing ALS factors, highlighting the improved effectiveness of multi-factorial prediction models to identify individuals at highest risk for ALS.}, } @article {pmid39249104, year = {2024}, author = {Hafsteinsdóttir, B and Farman, H and Lagerström, N and Zetterberg, H and Andersen, O and Novakova, L and Nellgård, B and Rosén, H and Malmeström, C and Rosenstein, I and Lycke, J and Axelsson, M}, title = {Neurofilament light chain as a diagnostic and prognostic biomarker in Guillain-Barré syndrome.}, journal = {Journal of neurology}, volume = {271}, number = {11}, pages = {7282-7293}, pmid = {39249104}, issn = {1432-1459}, support = {ALFGBG-722081//Swedish State Support for Clinical Research/ ; }, mesh = {Humans ; *Guillain-Barre Syndrome/blood/diagnosis/cerebrospinal fluid ; *Neurofilament Proteins/blood/cerebrospinal fluid ; Female ; Male ; Middle Aged ; *Biomarkers/blood/cerebrospinal fluid ; Adult ; Prognosis ; Aged ; Amyotrophic Lateral Sclerosis/blood/diagnosis/cerebrospinal fluid ; }, abstract = {BACKGROUND: Elevated neurofilament light chain (NfL) levels are associated with worse prognosis in Guillain-Barré syndrome (GBS). Our objectives were to determine the utility of serum NfL (sNfL), cerebrospinal fluid (CSF)/serum NfL ratio and NfL index as prognostic and diagnostic biomarkers for GBS.

METHODS: We measured NfL in serum and/or CSF obtained from 96 GBS patients between 1989 and 2014 in western Sweden. The sNfL Z-scores, NfL ratios and NfL indices were calculated. Outcome was determined with the GBS disability scale (GBSDS) at 3 and 12 months. NfL parameters in GBS were compared with healthy controls (HC), multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS).

RESULTS: The sNfL Z-score was higher for GBSDS > 2 at 3 months (median [IQR], 3.5 ng/L [3.2-4.0], vs 2.6 [1.7-3.4], p = 0.008) and at 12 months (3.6 ng/L [3.5-3.8] vs 2.6 [1.8-3.5], p = 0.049). NfL ratio and index were not associated with outcome. The area under the curve (AUC) for sNfL Z-score was 0.76 (95% CI 0.58-0.93, p < 0.0001) for GBSDS > 2 at 3 months. NfL ratio and index were lower in GBS than HC, MS, and ALS. The AUC for the NfL ratio was 0.66 (95% CI 0.55-0.78, p = 0.0018) and for the NfL index 0.86 (95% CI 0.78-0.93, p < 0.0001).

DISCUSSION: Our results confirm sNfL as prognostic biomarker for GBS and the precision was improved using the age-adjusted sNfL Z score. NfL index and Qalb are potential diagnostic biomarkers for GBS.}, } @article {pmid39246739, year = {2024}, author = {Li, S and Gui, J and Passarelli, MN and Andrew, AS and Sullivan, KM and Cornell, KA and Traynor, BJ and Stark, A and Chia, R and Kuenzler, RM and Pioro, EP and Bradley, WG and Stommel, EW}, title = {Genome-Wide and Transcriptome-Wide Association Studies on Northern New England and Ohio Amyotrophic Lateral Sclerosis Cohorts.}, journal = {Neurology. Genetics}, volume = {10}, number = {5}, pages = {e200188}, pmid = {39246739}, issn = {2376-7839}, support = {P30 CA023108/CA/NCI NIH HHS/United States ; }, abstract = {BACKGROUND AND OBJECTIVES: Amyotrophic lateral sclerosis (ALS) is an age-associated, fatal neurodegenerative disorder causing progressive paralysis and respiratory failure. The genetic architecture of ALS is still largely unknown.

METHODS: We performed a genome-wide association study (GWAS) and transcriptome-wide association study (TWAS) to understand genetic risk factors for ALS using a population-based case-control study of 435 ALS cases and 279 controls from Northern New England and Ohio. Single nucleotide polymorphism (SNP) genotyping was conducted using the Illumina NeuroChip array. Odds ratios were estimated using covariate-adjusted logistic regression. We also performed a genome-wide SNP-smoking interaction screening. TWAS analyses used PrediXcan to estimate associations between predicted gene expression levels across 15 tissues (13 brain tissues, skeletal muscle, and whole blood) and ALS risk.

RESULTS: GWAS analyses identified the p.A382T missense variant (rs367543041, p = 3.95E-6) in the TARDBP gene, which has previously been reported in association with increased ALS risk and was found to share a close affinity with the Sardinian haplotype. Both GWAS and TWAS analyses suggested that ZNF235 is associated with decreased ALS risk.

DISCUSSION: Our results support the need for future evaluation to clarify the role of these potential genetic risk factors for ALS and to understand genetic susceptibility to environmental risk factors.}, } @article {pmid39246712, year = {2024}, author = {Calderón-Garcidueñas, L and Cejudo-Ruiz, FR and Stommel, EW and González-Maciel, A and Reynoso-Robles, R and Torres-Jardón, R and Tehuacanero-Cuapa, S and Rodríguez-Gómez, A and Bautista, F and Goguitchaichvili, A and Pérez-Guille, BE and Soriano-Rosales, RE and Koseoglu, E and Mukherjee, PS}, title = {Single-domain magnetic particles with motion behavior under electromagnetic AC and DC fields are a fatal cargo in Metropolitan Mexico City pediatric and young adult early Alzheimer, Parkinson, frontotemporal lobar degeneration and amyotrophic lateral sclerosis and in ALS patients.}, journal = {Frontiers in human neuroscience}, volume = {18}, number = {}, pages = {1411849}, pmid = {39246712}, issn = {1662-5161}, abstract = {Metropolitan Mexico City (MMC) children and young adults exhibit overlapping Alzheimer and Parkinsons' diseases (AD, PD) and TAR DNA-binding protein 43 pathology with magnetic ultrafine particulate matter (UFPM) and industrial nanoparticles (NPs). We studied magnetophoresis, electron microscopy and energy-dispersive X-ray spectrometry in 203 brain samples from 14 children, 27 adults, and 27 ALS cases/controls. Saturation isothermal remanent magnetization (SIRM), capturing magnetically unstable FeNPs ~ 20nm, was higher in caudate, thalamus, hippocampus, putamen, and motor regions with subcortical vs. cortical higher SIRM in MMC ≤ 40y. Motion behavior was associated with magnetic exposures 25-100 mT and children exhibited IRM saturated curves at 50-300 mT associated to change in NPs position and/or orientation in situ. Targeted magnetic profiles moving under AC/AD magnetic fields could distinguish ALS vs. controls. Motor neuron magnetic NPs accumulation potentially interferes with action potentials, ion channels, nuclear pores and enhances the membrane insertion process when coated with lipopolysaccharides. TEM and EDX showed 7-20 nm NP Fe, Ti, Co, Ni, V, Hg, W, Al, Zn, Ag, Si, S, Br, Ce, La, and Pr in abnormal neural and vascular organelles. Brain accumulation of magnetic unstable particles start in childhood and cytotoxic, hyperthermia, free radical formation, and NPs motion associated to 30-50 μT (DC magnetic fields) are critical given ubiquitous electric and magnetic fields exposures could induce motion behavior and neural damage. Magnetic UFPM/NPs are a fatal brain cargo in children's brains, and a preventable AD, PD, FTLD, ALS environmental threat. Billions of people are at risk. We are clearly poisoning ourselves.}, } @article {pmid39246264, year = {2024}, author = {Iseli, LM and Poppe, C and Wangmo, T}, title = {Receiving and adjusting to a diagnosis of ALS: A qualitative study with informal caregivers.}, journal = {Palliative & supportive care}, volume = {}, number = {}, pages = {1-7}, doi = {10.1017/S1478951524001044}, pmid = {39246264}, issn = {1478-9523}, abstract = {OBJECTIVES: Diagnosis of amyotrophic lateral sclerosis (ALS) takes more than 1year from detection of first symptoms. The paper seeks to understand the ALS diagnostic process and adjustment from the perspective of informal caregivers.

METHODS: The data stems from an interview study with 9 current and 13 bereaved informal caregivers of people with ALS in Switzerland. The interviews were analyzed using thematic analysis.

RESULTS: We identified 3 key themes pertaining to ALS diagnosis. In the first theme, we present the close involvement of informal caregivers in the "diagnosis journey." Highlighted within this theme is the important role they play, which ultimately leads to diagnosis of ALS avoiding further delays. Second, we relay their perceptions on "diagnosis communication pitfalls" where they underlined empathy and planning from the part of medical professional, while communicating the terminal diagnosis of ALS. Participants' reactions and adjustments post-ALS diagnosis are described in "the aftermath of diagnosis." In this third theme, we highlight participants' shock and their need to rethink overall life plans and roles in their family.

SIGNIFICANCE OF THE RESULTS: Diagnosis communication that is clear, empathetic, and adjusted to the needs of the patients as well as their caregivers is critical. More work is needed to improve diagnosis communication for ALS patients. Receiving the diagnosis of ALS leads to complete changes in life of caregivers. It is therefore necessary that medical professionals provide adequate support that allows them to plan for their future.}, } @article {pmid39244645, year = {2025}, author = {Tang, IW and Hansen, J and Dickerson, AS and Weisskopf, MG}, title = {Occupational lead exposure and amyotrophic lateral sclerosis survival in the Danish National Patient Registry.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {26}, number = {1-2}, pages = {124-131}, pmid = {39244645}, issn = {2167-9223}, support = {P30 ES000002/ES/NIEHS NIH HHS/United States ; R01 ES019188/ES/NIEHS NIH HHS/United States ; T32 ES007069/ES/NIEHS NIH HHS/United States ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/mortality/epidemiology/diagnosis ; Male ; Denmark/epidemiology ; Female ; *Registries ; Middle Aged ; *Occupational Exposure/adverse effects ; Aged ; *Lead/adverse effects ; Adult ; }, abstract = {OBJECTIVES: We investigated the relationship between occupational lead exposure and amyotrophic lateral sclerosis (ALS) survival in Denmark.

METHODS: We identified 2,161 ALS cases diagnosed from 1982 to 2013 with at least 5 years of employment history before ALS diagnosis, via the Danish National Patient Registry. Cases were followed until March 2017. We defined lead exposure as never employed in a lead job, ever employed in a lead job, and ever employed in a lead job by exposure probability (<50% vs. ≥50%), excluding jobs held in the 5 years before diagnosis in main analyses. Survival was evaluated using Cox proportional hazards models and stratified by sex and age of diagnosis.

RESULTS: Median age of diagnosis was 63.5 years, and individuals in lead-exposed jobs were diagnosed at a younger age. Adjusted hazard ratios (aHR) were slightly decreased for men ever lead-exposed (aHR:0.92, 95%CI: 0.80, 1.05) and more so among those diagnosed at age 60-69 (lead ≥ 50% aHR: 0.66, 95%CI: 0.45, 0.98), but reversed for men diagnosed at age 70 and later (aHR: 2.03, 95%CI: 1.13, 3.64). No apparent pattern was observed among women.

CONCLUSIONS: Occupational lead exposure contributed to shorter survival among men diagnosed at older ages. The inverse associations observed for men diagnosed earlier could relate to possible healthy worker hire effect or health advantages of working in lead-exposed jobs. Our results are consistent with an adverse impact of lead exposure on ALS survival at older ages, with the age at which lead's effects on survival worsen later on among those in lead-exposed jobs.}, } @article {pmid39243983, year = {2025}, author = {Mohan, M and Mannan, A and Nauriyal, A and Singh, TG}, title = {Emerging targets in amyotrophic lateral sclerosis (ALS): The promise of ATP-binding cassette (ABC) transporter modulation.}, journal = {Behavioural brain research}, volume = {476}, number = {}, pages = {115242}, doi = {10.1016/j.bbr.2024.115242}, pmid = {39243983}, issn = {1872-7549}, mesh = {*Amyotrophic Lateral Sclerosis/metabolism ; Humans ; Animals ; *ATP-Binding Cassette Transporters/metabolism ; Signal Transduction/physiology ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative primarily affecting motor neurons, leading to disability and neuronal death, and ATP-Binding Cassette (ABC) transporter due to their role in drug efflux and modulation of various cellular pathways contributes to the pathogenesis of ALS. In this article, we extensively investigated various molecular and mechanistic pathways linking ALS transporter to the pathogenesis of ALS; this involves inflammatory pathways such as Mitogen-Activated Protein Kinase (MAPK), Phosphatidylinositol-3-Kinase/Protein Kinase B (PI3K/Akt), Toll-Like Receptor (TLR), Glycogen Synthase Kinase 3β (GSK-3β), Nuclear Factor Kappa-B (NF-κB), and Cyclooxygenase (COX). Oxidative pathways such as Astrocytes, Glutamate, Nuclear factor (erythroid-derived 2)-like 2 (Nrf2), Sirtuin 1 (SIRT-1), Forkhead box protein O (FOXO), Extracellular signal-regulated kinase (ERK). Additionally, we delve into the role of autophagic pathways like TAR DNA-binding protein 43 (TDP-43), AMP-activated protein kinase (AMPK), mammalian target of rapamycin (mTOR), and lastly, the apoptotic pathways. Furthermore, by understanding these intricate interactions, we aim to develop novel therapeutic strategies targeting ABC transporters, improving drug delivery, and ultimately offering a promising avenue for treating ALS.}, } @article {pmid39243146, year = {2024}, author = {Jimenez, JV and Tang, MJ and Wilson, MW and Morrison, AH and Ackrivo, J and Choi, PJ}, title = {Initiation of noninvasive ventilation in patients with amyotrophic lateral sclerosis.}, journal = {Muscle & nerve}, volume = {70}, number = {5}, pages = {1099-1103}, doi = {10.1002/mus.28250}, pmid = {39243146}, issn = {1097-4598}, support = {NIH NHLBI K23 HL-151879//Muscular Dystrophy Association/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy/physiopathology/complications ; *Noninvasive Ventilation/methods ; Female ; Male ; Middle Aged ; Aged ; Retrospective Studies ; *Respiratory Insufficiency/therapy/etiology/physiopathology ; Vital Capacity/physiology ; Hypercapnia/therapy/etiology/physiopathology ; Cohort Studies ; }, abstract = {INTRODUCTION/AIMS: Noninvasive ventilation (NIV) has been shown to improve survival and symptom burden in patients with amyotrophic lateral sclerosis (ALS). However, limited data exist regarding the clinical and physiological parameters at the time of NIV initiation. This study aimed to describe the clinical characteristics and respiratory physiological markers in a cohort of ALS patients with chronic respiratory failure.

METHODS: This is a single-center retrospective cohort study of patients with ALS assessed for NIV initiation between February 2012 and January 2021. NIV was initiated based on insurance eligibility criteria: daytime hypercapnia, defined by partial pressure of carbon dioxide (PaCO2) >45 mm Hg using diurnal transcutaneous CO2 (TcCO2) as a surrogate, a maximal inspiratory pressure (MIP) <60 cmH2O or forced vital capacity (FVC) <50% predicted normal.

RESULTS: We identified 335 patients with ALS and chronic respiratory failure referred to an outpatient home ventilation clinic for NIV initiation. The mean age was 64 years ±11; 151 (45%) were female, 326 (97%) were white, and 100 (29%) had bulbar-onset ALS. At the time of NIV initiation, the mean FVC was 64% ± 19%, the mean MIP; 41 cmH2O ± 17, and diurnal TcCO2; 40 ± 6 mmHg. The most common reasons for NIV initiation were MIP <60 cmH2O (58%) and multiple concomitant indications (28%). Within 1 year of NIV initiation, 126 (37%) patients were deceased.

DISCUSSION: We found that impairment in inspiratory force was the most common reason for NIV initiation and often preceded significant declines in FVC.}, } @article {pmid39242803, year = {2024}, author = {Monselise, EB and Vyazmensky, M and Scherf, T and Batushansky, A and Fishov, I}, title = {Author Correction: D-Glutamate production by stressed Escherichia coli gives a clue for the hypothetical induction mechanism of the ALS disease.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {20873}, doi = {10.1038/s41598-024-71813-5}, pmid = {39242803}, issn = {2045-2322}, } @article {pmid39242576, year = {2024}, author = {Phillips, MCL and Picard, M}, title = {Neurodegenerative disorders, metabolic icebergs, and mitohormesis.}, journal = {Translational neurodegeneration}, volume = {13}, number = {1}, pages = {46}, pmid = {39242576}, issn = {2047-9158}, mesh = {Humans ; *Neurodegenerative Diseases/metabolism/genetics ; *Mitochondria/metabolism ; Hormesis/physiology ; Animals ; }, abstract = {Neurodegenerative disorders are typically "split" based on their hallmark clinical, anatomical, and pathological features, but they can also be "lumped" by a shared feature of impaired mitochondrial biology. This leads us to present a scientific framework that conceptualizes Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD) as "metabolic icebergs" comprised of a tip, a bulk, and a base. The visible tip conveys the hallmark neurological symptoms, neurodegenerative regions, and neuronal protein aggregates for each disorder. The hidden bulk depicts impaired mitochondrial biology throughout the body, which is multifaceted and may be subdivided into impaired cellular metabolism, cell-specific mitotypes, and mitochondrial behaviours, functions, activities, and features. The underlying base encompasses environmental factors, especially modern industrial toxins, dietary lifestyles, and cognitive, physical, and psychosocial behaviours, but also accommodates genetic factors specific to familial forms of AD, PD, and ALS, as well as HD. Over years or decades, chronic exposure to a particular suite of environmental and genetic factors at the base elicits a trajectory of impaired mitochondrial biology that maximally impacts particular subsets of mitotypes in the bulk, which eventually surfaces as the hallmark features of a particular neurodegenerative disorder at the tip. We propose that impaired mitochondrial biology can be repaired and recalibrated by activating "mitohormesis", which is optimally achieved using strategies that facilitate a balanced oscillation between mitochondrial stressor and recovery phases. Sustainably harnessing mitohormesis may constitute a potent preventative and therapeutic measure for people at risk of, or suffering with, neurodegenerative disorders.}, } @article {pmid39242281, year = {2025}, author = {Amalia, R and Prasetya Wibawa, A and Surya Aditya, R and Andana Pohan, R and Tetteng, B and Zuhroh, L and Ainy Sadijah, N}, title = {Enhancing caregiver well being by integrating mindfulness and technology in amyotrophic lateral sclerosis care.}, journal = {Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia}, volume = {131}, number = {}, pages = {110819}, doi = {10.1016/j.jocn.2024.110819}, pmid = {39242281}, issn = {1532-2653}, mesh = {*Amyotrophic Lateral Sclerosis/therapy/psychology ; Humans ; *Mindfulness/methods ; *Caregivers/psychology ; *Quality of Life ; Mobile Applications ; Stress, Psychological/therapy/psychology ; }, abstract = {This letter discusses the pressing issue of caregiver burden in Amyotrophic Lateral Sclerosis (ALS) care, emphasizing the potential of mindfulness practices to alleviate stress and improve quality of life for caregivers. The integration of digital platforms, such as mindfulness apps, offers an accessible and effective solution, particularly in resource-limited settings. By adopting these strategies, we can enhance caregiver well-being and overall patient care, making it a crucial consideration for global health interventions.}, } @article {pmid39242252, year = {2024}, author = {Benmoussa, A and Assernannas, I and Maatoui-Belabbes, H and Dahmaoui, N and Qachouh, M and Cherkaoui, S and Lamchaheb, M and Rachid, M and Madani, A and Khoubila, N}, title = {[Acquired bone marrow aplasia in children and young adults under the age of 30: Experience of the Pediatric Hematology and Oncology Department of the 20 August Hospital, Casablanca].}, journal = {Bulletin du cancer}, volume = {111}, number = {10}, pages = {944-954}, doi = {10.1016/j.bulcan.2024.06.010}, pmid = {39242252}, issn = {1769-6917}, mesh = {Humans ; Male ; Female ; Infant ; Child, Preschool ; Child ; Adolescent ; Adult ; *Anemia, Aplastic/mortality/therapy ; Morocco/epidemiology ; Retrospective Studies ; Prognosis ; Time-to-Treatment ; *Cyclosporine/therapeutic use ; *Antilymphocyte Serum/therapeutic use ; *Hematopoietic Stem Cell Transplantation ; Treatment Outcome ; Delayed Diagnosis ; }, abstract = {Bone marrow aplasia is a rare and serious hematologic disorder. Although benign, it is a hematologic disorder whose prognosis can be poor and whose spontaneous development can be fatal. Treatment is long, difficult and costly. In developing countries, the mortality rate is high due to the difficulties of therapeutic management, both supportive and specific. We conducted a retrospective study of 92 cases of AM identified in the Pediatric Hematology and Oncology Department of the 20 Août University Hospital in Casablanca over a 10-year period (January 2010-January 2020). In this work, we present an overview of the situation and highlight the difficulties encountered in the management of AM in the Pediatric Hematology and Oncology Department of the University Hospital of Casablanca. In our study, the mean age was 19 years, ranging from 3 months to 29 years, with a peak in the 15-20 age group. The sex ratio (M/F) was 2.06, with a male predominance of 67%. In our series, only 35% of patients had complete bone marrow failure. An anemic syndrome was present in 92% of patients, and hemorrhagic and infectious syndromes were present in 70% and 41% of patients, respectively. The median time from diagnosis to treatment was 82 days. According to the Camitta score, 31% of our patients had mild AM, 41% had severe AM, and 28% had very severe AM. After etiologic evaluation, we concluded that 90% of the patients had idiopathic bone marrow aplasia, 2% had constitutional bone marrow aplasia, and 8% of the patients were suspected to have secondary bone marrow aplasia: post-hepatitis (3 cases), toxic (2 cases), drug-induced (1 case), and aplastic PNH (1 case). Mortality in the first three months after diagnosis was 21%. Sixty-nine percent of our patients received specific treatment: 28 were treated with cyclosporin (CIS) alone as first-line therapy, 20 received a combination of antilymphocyte serum (ALS) and cyclosporin, 2 received hematopoietic stem cell transplantation (HSCT), while 3 were treated with androgens alone. The overall response rate was 30% with CIS, 42% with ALS+CIS and 100% with HSCT. In our study, the overall death rate was 44%, while the one-year survival rate was 40%. It is important to note that septic shock was the leading cause of death (53% of deaths), followed by hemorrhagic shock (24%). This highlights the lack of hemodynamic resuscitation and symptomatic treatment. Our multivariate study defined the following risk factors as predictive of worse survival: age greater than 16 years (RR: 3.28; CI: 1.29-8.33; P=0.012), PNN less than 200 or very severe bone marrow aplasia (RR: 3.01; 1.1-8.08; P=0.028), and failure to receive any specific treatment (RR: 4.07; 1.77-9.35; P=0.0003). The high overall mortality in our series was due to several factors: inaccessibility to effective therapies, delayed diagnosis, failure to initiate specific treatment, inadequate symptomatic treatment, and geographical and financial inaccessibility.}, } @article {pmid39242198, year = {2024}, author = {Grassano, M and Canosa, A and D'Alfonso, S and Corrado, L and Brodini, G and Koumantakis, E and Cugnasco, P and Manera, U and Vasta, R and Palumbo, F and Mazzini, L and Gallone, S and Moglia, C and Dewan, R and Chia, R and Ding, J and Dalgard, C and Gibbs, RJ and Scholz, S and Calvo, A and Traynor, B and Chio, A}, title = {Intermediate HTT CAG repeats worsen disease severity in amyotrophic lateral sclerosis.}, journal = {Journal of neurology, neurosurgery, and psychiatry}, volume = {96}, number = {1}, pages = {100-102}, pmid = {39242198}, issn = {1468-330X}, } @article {pmid39241508, year = {2024}, author = {Zheng, X and Liu, J and Wang, S and Xiao, Y and Jiang, Q and Li, C and Shang, H}, title = {Total physical activity, plant-based diet and neurodegenerative diseases: A prospective cohort study of the UK biobank.}, journal = {Parkinsonism & related disorders}, volume = {128}, number = {}, pages = {107125}, doi = {10.1016/j.parkreldis.2024.107125}, pmid = {39241508}, issn = {1873-5126}, mesh = {Humans ; Male ; Female ; *Exercise/physiology ; Middle Aged ; United Kingdom/epidemiology ; Aged ; *Diet, Vegetarian ; *Neurodegenerative Diseases/epidemiology ; *Biological Specimen Banks ; Prospective Studies ; Alzheimer Disease/epidemiology ; Parkinson Disease/epidemiology ; Amyotrophic Lateral Sclerosis/epidemiology ; Adult ; Cohort Studies ; Diet, Plant-Based ; UK Biobank ; }, abstract = {INTRODUCTION: Neurodegenerative diseases (NDDs) result from a complex interplay of genetic, environmental and aging factors. A balanced diet and adequate physical activity (PA) are recognized as pivotal components among modifiable environmental factors. The independent impact on NDD incidence has been previously debated. This investigation seeks to delineate the association between PA and NDDs across various levels of adherence to a plant-based diet.

METHODS: In this study, a cohort of 368,934 participants from the UK Biobank was analyzed. Total physical activity (TPA) levels and healthful plant-based diet index (hPDI) were calculated and categorized. A multiple adjusted Cox model was utilized to evaluate the influence of TPA and hPDI on common NDDs, respectively.

RESULTS: Finally, 4602 identified cases diagnosed as Alzheimer's disease (AD), Parkinson's disease (PD) or amyotrophic lateral sclerosis (ALS). We found that higher TPA was significantly associated with a reduced risk of developing AD (Q3: HR 0.87; Q4: HR 0.78) and PD (Q3: HR 0.86; Q4: HR 0.81). The protective effect was further accentuated with adherence to a plant-based diet. However, these connections were not observed in the analysis of ALS regardless of dietary patterns.

CONCLUSION: Our findings underscore a significant association between higher TPA and reduced risks of AD and PD, with an enhanced effect observed in conjunction with a plant-based diet. This study contributes to addressing the knowledge gap regarding the combined impact of TPA and a plant-based diet on NDDs occurrence, providing insights into potential underlying mechanisms.}, } @article {pmid39241471, year = {2024}, author = {Casiraghi, V and Milone, I and Brusati, A and Peverelli, S and Doretti, A and Poletti, B and Maderna, L and Morelli, C and Ticozzi, N and Silani, V and Verde, F and Ratti, A}, title = {Quantification of serum TDP-43 and neurofilament light chain in patients with amyotrophic lateral sclerosis stratified by UNC13A genotype.}, journal = {Journal of the neurological sciences}, volume = {466}, number = {}, pages = {123210}, doi = {10.1016/j.jns.2024.123210}, pmid = {39241471}, issn = {1878-5883}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/blood/diagnosis ; Female ; Male ; *Neurofilament Proteins/blood/genetics ; Middle Aged ; Aged ; *Polymorphism, Single Nucleotide ; *DNA-Binding Proteins/genetics/blood ; *Genotype ; Biomarkers/blood ; Cohort Studies ; Adult ; Nerve Tissue Proteins ; }, abstract = {Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative condition affecting upper and/or lower motor neurons and characterized neuropathologically by TDP-43 proteinopathy. Given its role in ALS pathobiology, it is currently under debate whether TDP-43 might represent a suitable ALS biomarker to be measured in patients' biofluids. The rs12608932 A > C single nucleotide polymorphism in the UNC13A gene is a risk factor for ALS and patients homozygous for the high-risk C allele display a higher burden of TDP-43 neuropathology than homozygotes for the low-risk A allele, although the association with TDP-43 levels in biofluids has never been evaluated. In this study, we measured serum levels of TDP-43 and neurofilament light chain (NFL) by Simoa technology in a cohort of 69 ALS patients stratified according to the UNC13A rs12608932 genotype compared to 43 neurologically healthy controls. By multiple linear regression analysis, serum TDP-43 was significantly elevated in ALS patients compared to controls, with UNC13A AA and AC, but not CC, ALS patients showing higher serum TDP-43 levels than controls. We also confirmed that serum NFL concentration was increased in ALS patients, without any correlation with the UNC13A genotype. Our results indicate that serum TDP-43 is higher in ALS patients compared to controls and that, in contrast to NFL, this increase is specifically associated with the UNC13A rs12608932 AA and AC genotypes, but not with the high-risk CC genotype. Studies in larger cohorts will be needed to confirm these findings and to elucidate the biological link between serum TDP-43 levels and UNC13A genotype.}, } @article {pmid39241118, year = {2024}, author = {Sharkey, RJ and Cortese, F and Goodyear, BG and Korngut, LW and Jacob, SM and Sharkey, KA and Kalra, S and Nguyen, MD and Frayne, R and Pfeffer, G}, title = {Longitudinal analysis of glymphatic function in amyotrophic lateral sclerosis and primary lateral sclerosis.}, journal = {Brain : a journal of neurology}, volume = {147}, number = {12}, pages = {4026-4032}, pmid = {39241118}, issn = {1460-2156}, support = {//ALS Society of Canada/ ; //Barry Barrett Foundation/ ; //Rose Family Foundation/ ; //Hotchkiss Brain Institute/ ; /CAPMC/CIHR/Canada ; //Brain Canada Foundation/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology/diagnostic imaging/pathology ; Male ; Female ; Middle Aged ; Aged ; Longitudinal Studies ; *Glymphatic System/diagnostic imaging ; *Diffusion Tensor Imaging ; Disease Progression ; White Matter/diagnostic imaging/pathology ; Adult ; Motor Neuron Disease/physiopathology/diagnostic imaging/pathology ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder of motor neurons in the brain and spinal cord. Accumulation of misfolded proteins is central to the pathogenesis of ALS and the glymphatic system is emerging as a potential therapeutic target to reduce proteinopathy. Using diffusion tensor imaging analysis along the perivascular spaces (DTI-ALPS) to assess glymphatic function, we performed a longitudinal analysis of glymphatic function in ALS and compared it to a disorder in the motor neuron disease spectrum, primary lateral sclerosis (PLS). From a cohort of 45 participants from the Calgary site in the CALSNIC study (Canadian ALS Neuroimaging Consortium), including 18 ALS, 5 PLS and 22 control participants, DTI-ALPS was analysed and correlated to clinical features (age, sex, disease presentation, disease severity and progression rate) and white matter hyperintensity burden. This included longitudinal measurements at three time points, 4 months apart. The DTI-ALPS index was reduced in ALS participants compared with PLS and control participants across all three time points. There was no association with clinical factors; however, the index tended to decline with advancing age. Our study suggests heterogeneity in glymphatic dysfunction in motor neuron diseases that may be related to the underlying pathogenesis.}, } @article {pmid39240038, year = {2024}, author = {García-Casanova, PH and Pérez-Martínez, P and Sevilla, T and Doménech, R and León, M and Vázquez-Costa, JF}, title = {Impact of SARS-CoV-2 infection and COVID-19 pandemic on the morbidity and mortality of amyotrophic lateral sclerosis patients in Valencia, Spain.}, journal = {European journal of neurology}, volume = {31}, number = {12}, pages = {e16465}, pmid = {39240038}, issn = {1468-1331}, support = {JR19/00030//Instituto de Salud Carlos III/ ; PI 21/00737//Instituto de Salud Carlos III/ ; }, mesh = {Humans ; *COVID-19/mortality/epidemiology ; *Amyotrophic Lateral Sclerosis/epidemiology/mortality ; Spain/epidemiology ; Female ; Male ; Middle Aged ; Aged ; *Hospitalization/statistics & numerical data ; Risk Factors ; Noninvasive Ventilation/statistics & numerical data ; Pandemics ; SARS-CoV-2 ; }, abstract = {BACKGROUND AND PURPOSE: The purpose was to describe the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, hospitalization for coronavirus disease 2019 (COVID-19) and related death and to assess the impact of the pandemic in the survival of amyotrophic lateral sclerosis (ALS) patients.

METHODS: The risk of SARS-CoV-2 infection, hospitalization for COVID-19 and related death was assessed in ALS patients alive between March 2020 and July 2022. To evaluate its impact in the overall survival of ALS patients, the survival of patients who died before and during the pandemic was compared.

RESULTS: Amongst 263 ALS patients alive during the pandemic, 62 got infected during the study period (infection rate 14.34 per 100 person-years). Most infections (68%) occurred during the sixth wave (November 2021 to January 2022) and most patients (67%) were vaccinated at the time of infection. The hospitalization rate due to COVID-19 was 4.16 per 100 person-years. The multivariable model confirmed non-invasive ventilation (NIV) use prior to infection as a risk factor for hospitalization (odds ratio [OR] = 7.96, p = 0.003) and COVID-19 vaccination as a protective factor (OR = 0.093, p = 0.025) independent of age, sex and gastrostomy. Within 30 days after infection, 7% of non-ventilated patients started NIV and five patients (8.06%) died, of whom four were previously ventilated. The median survival of ALS patients was similar before and during the pandemic and no effect was found in the Cox regression model (hazard ratio 1.02, p = 0.89).

CONCLUSIONS: This study shows a high risk of severe COVID-19 amongst ALS patients requiring NIV. Nevertheless, the pandemic showed no impact in the overall survival of ALS patients, probably due to a high vaccination rate and an adequate access to healthcare resources.}, } @article {pmid39239358, year = {2024}, author = {Segerstrom, SC and Kasarskis, EJ}, title = {The Seattle Amyotrophic Lateral Sclerosis (ALS) Patient Project Database: observational, longitudinal, dyadic characterization of people with ALS and their partners.}, journal = {Health psychology and behavioral medicine}, volume = {12}, number = {1}, pages = {2396137}, pmid = {39239358}, issn = {2164-2850}, support = {R03 NS128748/NS/NINDS NIH HHS/United States ; R16 NS129748/NS/NINDS NIH HHS/United States ; }, abstract = {INTRODUCTION: The median survival time in ALS is approximately 3 years, but survival times range from less than a year to more than 10 years and much variance in disease course remains to be explained. As is true for physical outcomes, there is considerable variance in QOL, which is influenced by psychological health, coping, and social support, among other psychosocial factors. The Seattle ALS Patient Project Database (SALSPPD) provides a unique opportunity for researchers to address established and novel hypotheses about disease progression and QOL in ALS.

METHODS: The SALSPPD is a longitudinal dataset of people with ALS (n = 143) and their partners (spouses, significant others, or caregivers; n = 123) from clinics and community-based ALS support groups. Participants were interviewed in their homes every 3 months for up to 18 months between March 1987 and August 1989. Follow-up phone calls were completed in 1990, 1994, and 2008, primarily to ascertain disease outcomes.

RESULTS: The provided data dictionary includes details of the over 500 variables measured in the study, which have been subsetted into domain datasets. Domains address physical, psychological, social, and behavioral status on the person with ALS and their partners. Missing data were coded according to their mechanism. Data are available in two formats: The person-level (wide) databases and the time-level (long) databases.

DISCUSSION: The SALSPPD will provide a rich resource to scientists interested in the natural history of ALS, psychosocial effects on ALS outcomes and vice versa, and psychosocial and disease outcomes of treatments.}, } @article {pmid39239150, year = {2024}, author = {Vidovic, M and Lapp, HS and Weber, C and Plitzko, L and Seifert, M and Steinacker, P and Otto, M and Hermann, A and Günther, R}, title = {Comparative analysis of neurofilaments and biomarkers of muscular damage in amyotrophic lateral sclerosis.}, journal = {Brain communications}, volume = {6}, number = {5}, pages = {fcae288}, pmid = {39239150}, issn = {2632-1297}, abstract = {Diagnosis of the fatal neurodegenerative disease amyotrophic lateral sclerosis is challenging. Neurofilaments, indicative of neuronal damage, along with creatine kinase, creatinine, myoglobin, and troponin T, representing muscular damage, have been identified as promising fluid biomarkers. This study aims to comprehensively assess and compare their diagnostic and prognostic potential in a 'real-world' cohort of patients with amyotrophic lateral sclerosis. About 77 patients with amyotrophic lateral sclerosis and its clinical variants, and 26 age- and sex-matched controls with various neuromuscular and neurodegenerative diseases, were retrospectively included in this monocentric, cross-sectional study. Neurofilaments in cerebrospinal fluid and biomarkers of muscular damage in serum were measured and correlated with demographic features, motor function, survival time, clinical phenotypes, and the extent of upper and lower motor neuron involvement. Neurofilament, myoglobin, and troponin T concentrations were higher in patients with amyotrophic lateral sclerosis compared to disease controls. Higher neurofilament levels correlated with lower motor function and faster disease progression rate, while higher creatine kinase and creatinine concentrations were linked to preserved motor function. In contrast, troponin T elevation indicated poorer fine and gross motor functions. Increased neurofilament levels were associated with shorter survival, whereas biomarkers of muscular damage lacked survival correlation. Neurofilament concentrations were higher in classical amyotrophic lateral sclerosis than in progressive muscular atrophy, while myoglobin and troponin T levels were elevated in progressive muscular atrophy compared to primary lateral sclerosis. Neurofilaments were predominantly linked to upper motor neuron involvement. Our findings confirmed the robust diagnostic and prognostic value of neurofilaments in amyotrophic lateral sclerosis. Elevated neurofilament concentrations were associated with higher disease severity, faster disease progression, shorter survival, and predominant upper motor neuron degeneration. Biomarkers of muscular damage were inferior in distinguishing amyotrophic lateral sclerosis from other neuromuscular and neurodegenerative diseases. However, they may serve as complementary biomarkers and support in discriminating clinical variants of amyotrophic lateral sclerosis.}, } @article {pmid39239063, year = {2024}, author = {Pezeshgi, S and Ghaderi, S and Mohammadi, S and Karimi, N and Ziaadini, B and Mohammadi, M and Fatehi, F}, title = {Diffusion tensor imaging biomarkers and clinical assessments in amyotrophic lateral sclerosis (ALS) patients: an exploratory study.}, journal = {Annals of medicine and surgery (2012)}, volume = {86}, number = {9}, pages = {5080-5090}, pmid = {39239063}, issn = {2049-0801}, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive loss of upper and lower motor neurons. Biomarkers are needed to improve diagnosis, gauge progression, and evaluate treatment. Diffusion tensor imaging (DTI) is a promising biomarker for detecting microstructural alterations in the white matter tracts. This study aimed to assess DTI metrics as biomarkers and to examine their relationship with clinical assessments in patients with ALS. Eleven patients with ALS and 21 healthy controls (HCs) underwent 3T MRI with DTI. DTI metrics, including fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD), were compared between key motor and extra-motor tract groups. Group comparisons and correlations between DTI metrics also correlated with clinical scores of disability (ALSFRS-R), muscle strength (dynamometry), and motor unit loss (MUNIX). Widespread differences were found between patients with ALS and HCs in DTI metrics, including decreased FA and increased diffusivity metrics. However, MD and RD are more sensitive metrics for detecting white matter changes in patients with ALS. Significant interhemispheric correlations between the tract DTI metrics were also observed. DTI metrics showed symmetry between the hemispheres and correlated with the clinical assessments. MD, RD, and AD increases significantly correlated with lower ALSFRS-R and MUNIX scores and weaker dynamometry results. DTI reveals microstructural damage along the motor and extra-motor regions in ALS patients. DTI metrics can serve as quantitative neuroimaging biomarkers for diagnosis, prognosis, monitoring of progression, and treatment. Combined analysis of imaging, electrodiagnostic, and functional biomarkers shows potential for characterizing disease pathophysiology and progression.}, } @article {pmid39236857, year = {2024}, author = {Reiter, RJ and Sharma, RN and Manucha, W and Rosales-Corral, S and Almieda Chuffa, LG and Loh, D and Luchetti, F and Balduini, W and Govitrapong, P}, title = {Dysfunctional mitochondria in age-related neurodegeneration: Utility of melatonin as an antioxidant treatment.}, journal = {Ageing research reviews}, volume = {101}, number = {}, pages = {102480}, doi = {10.1016/j.arr.2024.102480}, pmid = {39236857}, issn = {1872-9649}, mesh = {*Melatonin/metabolism/pharmacology/therapeutic use ; Humans ; *Antioxidants/pharmacology/therapeutic use ; *Mitochondria/metabolism/drug effects ; *Aging/metabolism/drug effects ; Animals ; *Neurodegenerative Diseases/metabolism/drug therapy ; Oxidative Stress/drug effects ; }, abstract = {Mitochondria functionally degrade as neurons age. Degenerative changes cause inefficient oxidative phosphorylation (OXPHOS) and elevated electron leakage from the electron transport chain (ETC) promoting increased intramitochondrial generation of damaging reactive oxygen and reactive nitrogen species (ROS and RNS). The associated progressive accumulation of molecular damage causes an increasingly rapid decline in mitochondrial physiology contributing to aging. Melatonin, a multifunctional free radical scavenger and indirect antioxidant, is synthesized in the mitochondrial matrix of neurons. Melatonin reduces electron leakage from the ETC and elevates ATP production; it also detoxifies ROS/RNS and via the SIRT3/FOXO pathway it upregulates activities of superoxide dismutase 2 and glutathione peroxidase. Melatonin also influences glucose processing by neurons. In neurogenerative diseases, neurons often adopt Warburg-type metabolism which excludes pyruvate from the mitochondria causing reduced intramitochondrial acetyl coenzyme A production. Acetyl coenzyme A supports the citric acid cycle and OXPHOS. Additionally, acetyl coenzyme A is a required co-substrate for arylalkylamine-N-acetyl transferase, which rate limits melatonin synthesis; therefore, melatonin production is diminished in cells that experience Warburg-type metabolism making mitochondria more vulnerable to oxidative stress. Moreover, endogenously produced melatonin diminishes during aging, further increasing oxidative damage to mitochondrial components. More normal mitochondrial physiology is preserved in aging neurons with melatonin supplementation.}, } @article {pmid39236792, year = {2024}, author = {Hattori, H and Osumi, K and Tanaka, M and Arai, T and Nishimura, K and Yamamoto, N and Sakamoto, K and Goto, Y and Sugawara, Y}, title = {Discovery of 5-phenyl-3-ureidothiophene-2-carboxamides as protective agents for ALS patient iPSC-derived motor neurons.}, journal = {Bioorganic & medicinal chemistry letters}, volume = {113}, number = {}, pages = {129935}, doi = {10.1016/j.bmcl.2024.129935}, pmid = {39236792}, issn = {1464-3405}, mesh = {Humans ; *Induced Pluripotent Stem Cells/drug effects/metabolism ; *Amyotrophic Lateral Sclerosis/drug therapy ; *Motor Neurons/drug effects/metabolism ; *Neuroprotective Agents/pharmacology/chemistry/chemical synthesis ; *Drug Discovery ; Structure-Activity Relationship ; Molecular Structure ; Thiophenes/chemistry/pharmacology/chemical synthesis ; Protein Serine-Threonine Kinases/antagonists & inhibitors/metabolism ; Protein Kinase Inhibitors/pharmacology/chemistry/chemical synthesis ; Dose-Response Relationship, Drug ; Superoxide Dismutase-1/metabolism/genetics ; Intracellular Signaling Peptides and Proteins ; }, abstract = {We discovered novel neuroprotective compounds by phenotypic screening using SOD1-mutant amyotrophic lateral sclerosis (ALS) patient induced pluripotent stem cell (iPSC)-derived motor neurons. Mechanistic analysis showed that the protective effect of initial hit compound 1 was likely due to the inhibition of MAP4Ks, including MAP4K4, a member of the MAP4K kinase family. Structural transformation led to compound 15f, which showed improved MAP4K4 inhibitory activity and superior neuroprotective effects compared to 1 in motor neurons. The results suggest that structural optimization based on MAP4K4 inhibitory activity might improve the neuroprotective effect of this series of compounds.}, } @article {pmid39236307, year = {2024}, author = {Doneddu, PE and Gallo, C and Gentile, L and Cocito, D and Falzone, Y and Di Stefano, V and Inghilleri, M and Cosentino, G and Matà, S and Mazzeo, A and Filosto, M and Peci, E and Sorrenti, B and Brighina, F and Moret, F and Vegezzi, E and Sperti, M and Risi, B and Nobile-Orazio, E and , }, title = {Comparison of the diagnostic accuracy of the 2010 European Federation of Neurological Societies/Peripheral Nerve Society and American Association of Electrodiagnostic Medicine diagnostic criteria for multifocal motor neuropathy.}, journal = {European journal of neurology}, volume = {31}, number = {12}, pages = {e16444}, pmid = {39236307}, issn = {1468-1331}, support = {IIR-ITA-BXLT-001955/ IISR-2017-104226//Takeda Italia SPA/ ; //Fondazione Humanitas per la Ricerca/ ; }, mesh = {Humans ; Male ; Middle Aged ; Female ; *Electrodiagnosis/standards/methods ; *Sensitivity and Specificity ; Retrospective Studies ; Aged ; *Neural Conduction/physiology ; *Societies, Medical/standards ; *Polyneuropathies/diagnosis/physiopathology ; Adult ; Europe ; Motor Neuron Disease/diagnosis/physiopathology ; United States ; Amyotrophic Lateral Sclerosis/diagnosis/physiopathology ; }, abstract = {BACKGROUND AND PURPOSE: This study was undertaken to compare the sensitivity and specificity of the 2010 European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) diagnostic criteria for multifocal motor neuropathy (MMN) with those of the American Association of Electrodiagnostic Medicine (AAEM).

METHODS: Sensitivity and specificity of the two sets of criteria were retrospectively evaluated in 53 patients with MMN and 280 controls with axonal peripheral neuropathy, inflammatory demyelinating polyneuropathy, or amyotrophic lateral sclerosis. Comparison of the utility of nerve conduction studies with different numbers of nerves examined was also assessed.

RESULTS: The 2010 EFNS/PNS criteria had a sensitivity of 47% for definite MMN and 57% for probable/definite MMN, whereas the AAEM criteria had a sensitivity of 28% for definite MMN and 53% for probable/definite MMN. The sensitivity of the AAEM criteria was higher when utilizing area compared to amplitude reduction to define conduction block. Using supportive criteria, the sensitivity of the 2010 EFNS/PNS criteria for probable/definite MMN increased to 64%, and an additional 36% patients fulfilled the criteria (possible MMN). Specificity values for definite and probable/definite MMN were slightly higher with the AAEM criteria (100%) compared to the EFNS/PNS criteria (98.5% and 97%). Extended nerve conduction studies yielded slightly increased diagnostic sensitivity for both sets of criteria without significantly affecting specificity.

CONCLUSIONS: In our patient populations, the 2010 EFNS/PNS criteria demonstrated higher sensitivity but slightly lower specificity compared to the AAEM criteria. Extended nerve conduction studies are advised to achieve slightly higher sensitivity while maintaining very high specificity.}, } @article {pmid39235524, year = {2024}, author = {Poletti, B and Aiello, EN and Consonni, M and Iazzolino, B and Torre, S and Solca, F and Faltracco, V and Telesca, A and Palumbo, F and Dalla Bella, E and Bersano, E and Riva, N and Verde, F and Messina, S and Doretti, A and Maranzano, A and Morelli, C and Calvo, A and Silani, V and Lauria, G and Chiò, A and Ticozzi, N}, title = {Prevalence and motor-functional correlates of frontotemporal-spectrum disorders in a large cohort of non-demented ALS patients.}, journal = {Journal of neurology}, volume = {271}, number = {10}, pages = {6944-6955}, pmid = {39235524}, issn = {1432-1459}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/epidemiology/physiopathology/complications ; Male ; Female ; Middle Aged ; Aged ; Prevalence ; Frontotemporal Dementia/physiopathology/epidemiology ; Cohort Studies ; Neuropsychological Tests ; Disease Progression ; Adult ; }, abstract = {BACKGROUND: This study aimed at (1) delivering generalizable estimates of the prevalence of frontotemporal-spectrum disorders (FTSDs) in non-demented ALS patients and (2) exploring their motor-functional correlates.

METHODS: N = 808 ALS patients without FTD were assessed for motor-functional outcomes-i.e., disease duration, severity (ALSFRS-R), progression rate (ΔFS), and stage (King's and Milano-Torino-MiToS-systems)-cognition-via the cognitive section of the Edinburgh Cognitive and Behavioural ALS Screen (ECAS)-and behaviour-via the ECAS-Carer Interview. Neuropsychological phenotypes were retrieved via Strong's revised criteria-i.e., ALS cognitively and behaviourally normal (ALScbn) or cognitively and/or behaviourally impaired (ALSci/bi/cbi).

RESULTS: Defective ECAS-Total performances were detected in ~ 29% of patients, with the ECAS-Executive being failed by the highest number of patients (~ 30%), followed by the ECAS-Language, -Fluency, and -Memory (~ 15-17%) and -Visuospatial (~ %8). Apathy was the most frequent behavioural change (~ 28%), followed by loss of sympathy/empathy (~ 13%); remaining symptoms were reported in < 4% of patients. The distribution of Strong's classifications was as follows: ALScbn: 46.7%; ALSci/bi/cbi: 22.9%/20.0%/10.4%. Multinomial regressions on Strong's classifications revealed that lower ALSFRS-R scores were associated with a higher probability of ALSbi and ALScbi classifications (p ≤ .008). Higher King's and MiToS stages were associated with a higher probability of ALSbi classification (p ≤ .031).

CONCLUSIONS: FTSDs affect ~ 50% of non-demented ALS patients, with cognitive deficits being as frequent as behavioural changes. A higher degree of motor-functional involvement is associated with worse behavioural outcomes-with this link being weaker for cognitive deficits.}, } @article {pmid39234934, year = {2024}, author = {Mao, M and Zeng, W and Zheng, Y and Fan, W and Yao, Y}, title = {Fasudil attenuates syncytin-1-mediated activation of microglia and impairments of motor neurons and motor function in mice.}, journal = {Drug development research}, volume = {85}, number = {6}, pages = {e22254}, doi = {10.1002/ddr.22254}, pmid = {39234934}, issn = {1098-2299}, support = {81860245//National Natural Science Foundation of China/ ; [2019]5664//Department of Science and Technology of Guizhou Province/ ; GZSYBS[2017]01//Doctor Fund of Guizhou Provincial People's Hospital/ ; GZSYQN[2018]09//Youth Fund of Guizhou Provincial People's Hospital/ ; }, mesh = {Animals ; *Microglia/drug effects/metabolism ; *Motor Neurons/drug effects/metabolism ; Mice ; *Mice, Inbred C57BL ; *1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine/analogs & derivatives/pharmacology ; Gene Products, env ; Amyotrophic Lateral Sclerosis/drug therapy/metabolism ; Pregnancy Proteins/metabolism ; Male ; Cytokines/metabolism ; Disease Models, Animal ; Motor Activity/drug effects ; Spinal Cord/metabolism/drug effects ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease. Syncytin-1 (Syn), an envelope glycoprotein encoded by the env gene of the human endogenous retrovirus-W family, has been resorted to be highly expressed in biopsies from the muscles from ALS patients; however, the specific regulatory role of Syn during ALS progression remains uncovered. In this study, C57BL/6 mice were injected with adeno-associated virus-overexpressing Syn, with or without Fasudil administration. The Syn expression was assessed by quantitative real-time polymerase chain reaction and immunohistochemistry analysis. The histological change of anterior tibial muscles was determined by hematoxylin-eosin staining. Qualitative ultrastructural analysis of electron micrographs obtained from lumbar spinal cords was carried out. Serum inflammatory cytokines were assessed by enzyme linked immunosorbent assay (ELISA) assay and motor function was recorded using Basso, Beattie, and Bresnahan (BBB) scoring, climbing test and treadmill running test. Immunofluorescence and western blot assays were conducted to examine microglial- and motor neurons-related proteins. Syn overexpression significantly caused systemic inflammatory response, muscle tissue lesions, and motor dysfunction in mice. Meanwhile, Syn overexpression promoted the impairment of motor neuron, evidenced by the damaged structure of the neurons and reduced expression of microtubule-associated protein 2, HB9, neuronal nuclei and neuron-specific enolase in Syn-induced mice. In addition, Syn overexpression greatly promoted the expression of CD16/CD32 and inducible nitric oxide synthase (M1 phenotype markers), and reduced the expression of CD206 and arginase 1 (M2 phenotype markers). Importantly, the above changes caused by Syn overexpression were partly abolished by Fasudil administration. This study provides evidence that Syn-activated microglia plays a pivotal role during the progression of ALS.}, } @article {pmid39233852, year = {2024}, author = {Gilbert, JW and Kennedy, Z and Godinho, BMDC and Summers, A and Weiss, A and Echeverria, D and Bramato, B and McHugh, N and Cooper, D and Yamada, K and Hassler, M and Tran, H and Gao, FB and Brown, RH and Khvorova, A}, title = {Identification of selective and non-selective C9ORF72 targeting in vivo active siRNAs.}, journal = {Molecular therapy. Nucleic acids}, volume = {35}, number = {3}, pages = {102291}, pmid = {39233852}, issn = {2162-2531}, support = {R01 NS104022/NS/NINDS NIH HHS/United States ; }, abstract = {A hexanucleotide (G4C2) repeat expansion (HRE) within intron one of C9ORF72 is the leading genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). C9ORF72 haploinsufficiency, formation of RNA foci, and production of dipeptide repeat (DPR) proteins have been proposed as mechanisms of disease. Here, we report the first example of disease-modifying siRNAs for C9ORF72 driven ALS/FTD. Using a combination of reporter assay and primary cortical neurons derived from a C9-ALS/FTD mouse model, we screened a panel of more than 150 fully chemically stabilized siRNAs targeting different C9ORF72 transcriptional variants. We demonstrate the lack of correlation between siRNA efficacy in reporter assay versus native environment; repeat-containing C9ORF72 mRNA variants are found to preferentially localize to the nucleus, and thus C9ORF72 mRNA accessibility and intracellular localization have a dominant impact on functional RNAi. Using a C9-ALS/FTD mouse model, we demonstrate that divalent siRNAs targeting C9ORF72 mRNA variants specifically or non-selectively reduce the expression of C9ORF72 mRNA and significantly reduce DPR proteins. Interestingly, siRNA silencing all C9ORF72 mRNA transcripts was more effective in removing intranuclear mRNA aggregates than targeting only HRE-containing C9ORF72 mRNA transcripts. Combined, these data support RNAi-based degradation of C9ORF72 as a potential therapeutic paradigm.}, } @article {pmid39233624, year = {2024}, author = {Garnier, M and Camdessanché, JP and Cassereau, J and Codron, P}, title = {From suspicion to diagnosis: exploration strategy for suspected amyotrophic lateral sclerosis.}, journal = {Annals of medicine}, volume = {56}, number = {1}, pages = {2398199}, pmid = {39233624}, issn = {1365-2060}, mesh = {*Amyotrophic Lateral Sclerosis/diagnosis/physiopathology ; Humans ; Diagnosis, Differential ; Electromyography/methods ; }, abstract = {The diagnosis of amyotrophic lateral sclerosis (ALS) is based on evidence of upper and lower motor neuron degeneration in the bulbar, cervical, thoracic, and lumbar regions in a patient with progressive motor weakness, in the absence of differential diagnosis. Despite these well-defined criteria, ALS can be difficult to diagnose, given the wide variety of clinical phenotypes. Indeed, the central or peripheral location of the disease varies with a spectrum ranging from predominantly central to exclusively peripheral, symptoms can be extensive or limited to the limbs, bulbar area or respiratory muscles, and the duration of the disease may range from a few months to several decades. In the absence of a specific test, the diagnostic strategy relies on clinical, electrophysiological, biological and radiological investigations to confirm the disease and exclude ALS mimics. The main challenge is to establish a diagnosis based on robust clinical and paraclinical evidence without delaying treatment initiation by increasing the number of additional tests. This approach requires a thorough knowledge of the phenotypes of ALS and its main differential diagnoses.}, } @article {pmid39233146, year = {2024}, author = {Wang, H and Liu, S and Sun, Y and Chen, C and Hu, Z and Li, Q and Long, J and Yan, Q and Liang, J and Lin, Y and Yang, S and Lin, M and Liu, X and Wang, H and Yu, J and Yi, F and Tan, Y and Yang, Y and Chen, N and Ai, Q}, title = {Target modulation of glycolytic pathways as a new strategy for the treatment of neuroinflammatory diseases.}, journal = {Ageing research reviews}, volume = {101}, number = {}, pages = {102472}, doi = {10.1016/j.arr.2024.102472}, pmid = {39233146}, issn = {1872-9649}, mesh = {Humans ; *Glycolysis/physiology ; *Neuroinflammatory Diseases/metabolism/drug therapy ; Animals ; Aging/metabolism ; }, abstract = {Neuroinflammation is an innate and adaptive immune response initiated by the release of inflammatory mediators from various immune cells in response to harmful stimuli. While initially beneficial and protective, prolonged or excessive neuroinflammation has been identified in clinical and experimental studies as a key pathological driver of numerous neurological diseases and an accelerant of the aging process. Glycolysis, the metabolic process that converts glucose to pyruvate or lactate to produce adenosine 5'-triphosphate (ATP), is often dysregulated in many neuroinflammatory disorders and in the affected nerve cells. Enhancing glucose availability and uptake, as well as increasing glycolytic flux through pharmacological or genetic manipulation of glycolytic enzymes, has shown potential protective effects in several animal models of neuroinflammatory diseases. Modulating the glycolytic pathway to improve glucose metabolism and ATP production may help alleviate energy deficiencies associated with these conditions. In this review, we examine six neuroinflammatory diseases-stroke, Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), and depression-and provide evidence supporting the role of glycolysis in their treatment. We also explore the potential link between inflammation-induced aging and glycolysis. Additionally, we briefly discuss the critical role of glycolysis in three types of neuronal cells-neurons, microglia, and astrocytes-within physiological processes. This review highlights the significance of glycolysis in the pathology of neuroinflammatory diseases and its relevance to the aging process.}, } @article {pmid39232594, year = {2024}, author = {Martínez-Payá, JJ and Ríos-Díaz, J and Del Baño-Aledo, ME and Hervás, D and Tembl-Ferrairó, JI and Sevilla-Mantecón, T and Vázquez-Costa, JF}, title = {The cross-sectional area of the median nerve: An independent prognostic biomarker in amyotrophic lateral sclerosis.}, journal = {Neurologia}, volume = {39}, number = {7}, pages = {564-572}, doi = {10.1016/j.nrleng.2024.07.003}, pmid = {39232594}, issn = {2173-5808}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis ; Male ; Middle Aged ; Female ; *Median Nerve/diagnostic imaging ; Prognosis ; *Biomarkers ; Aged ; *Ultrasonography ; Disease Progression ; Cohort Studies ; }, abstract = {INTRODUCTION: Ultrasound changes in the cross-sectional area of the median nerve (CSAmn) could be of interest as biomarkers in patients with amyotrophic lateral sclerosis (ALS).

METHODS: Eighty-four ALS patients (51 men [60.7%]; mean 62.0 [SD 11.46] years old) and forty-six controls (27 men [58.7%]; mean 59.9 [SD 8.08] years old) of two different cohorts were recruited between September 2013 and February 2018. The CSAmn was measured bilaterally in each cohort, by two different examiners with two different ultrasound machines (one in each cohort). Its association with clinical variables (disease duration, muscle strength, disability, progression rate and tracheostomy-free survival) was assessed.

RESULTS: The CSAmn was smaller in patients than in controls, and the study cohort did not influence its values. A mild correlation between the strength of the wrist flexor and the CSAmn was found. In the multivariable analysis, the probability of this association being true was 90%. In the cox regression, both a faster progression rate and a larger CSAmn independently predicted poor survival (HR=4.29, [Cr.I95%: 2.71-6.80], p<0.001; and HR=1.14, [Cr.I95%: 1.03-1.25], p=0.01), after adjusting by age, body mass index, bulbar onset, and diagnostic delay.

CONCLUSIONS: The CSAmn is an easy to assess biomarker that seems reliable and reproducible. Our data also suggest that it could act as a progression and prognostic biomarker in ALS patients. Longitudinal studies with repeated measures are warranted to confirm its usefulness in the clinical practice.}, } @article {pmid39232248, year = {2024}, author = {Borchert, GA and Shanks, ME and Whitfield, J and Clouston, P and Raji, S and Sperring, S and Thompson, JA and Xue, K and De Silva, SR and Downes, SM and MacLaren, RE and Cehajic-Kapetanovic, J}, title = {Expanding the genotypic and phenotypic spectra with a novel variant in the ciliopathy gene, CFAP410, associated with selective cone degeneration.}, journal = {Ophthalmic genetics}, volume = {45}, number = {6}, pages = {633-639}, pmid = {39232248}, issn = {1744-5094}, mesh = {Humans ; Female ; Adult ; *Ciliopathies/genetics ; *Pedigree ; *Phenotype ; Retrospective Studies ; Genotype ; Cone Dystrophy/genetics/diagnosis ; Consanguinity ; Visual Acuity/physiology ; Tomography, Optical Coherence ; Mutation ; Homozygote ; }, abstract = {BACKGROUND: CFAP410 (Cilia and Flagella Associated Protein 410) encodes a protein that has an important role in the development and function of cilia. In ophthalmology, pathogenic variants in CFAP410 have been described in association with cone rod dystrophy, retinitis pigmentosa, with or without macular staphyloma, or with systemic abnormalities such as skeletal dysplasia and amyotrophic lateral sclerosis. Herein, we report a consanguineous family with a novel homozygous CFAP410 c.335_346del variant with cone only degeneration and no systemic features.

METHODS: A retrospective analysis of ophthalmic history, examination, retinal imaging, electrophysiology and microperimetry was performed as well as genetic testing with in silico pathogenicity predictions and a literature review.

RESULTS: A systemically well 28-year-old female of Pakistani ethnicity with parental consanguinity and no relevant family history, presented with childhood-onset poor central vision and photophobia. Best-corrected visual acuity and colour vision were reduced (0.5 LogMAR, 6/17 Ishihara plates (right) and 0.6 LogMAR, 3/17 Ishihara plates (left). Fundus examination showed no pigmentary retinopathy, no macular staphyloma and autofluorescence was unremarkable. Optical coherence tomography showed subtle signs of intermittent disruption of the ellipsoid zone. Microperimetry demonstrated a reduction in central retinal sensitivity. Electrodiagnostic testing confirmed a reduction in cone-driven responses. Whole-genome sequencing identified an in-frame homozygous deletion of 12 base pairs at c.335_346del in CFAP410.

CONCLUSIONS: The non-syndromic cone dystrophy phenotype reported herein expands the genotypic and phenotypic spectra of CFAP410-associated ciliopathies and highlights the need for light of potential future genetic therapies.}, } @article {pmid39231585, year = {2025}, author = {Kato, C and Morimoto, S and Takahashi, S and Namba, S and Wang, QS and Okada, Y and Okano, H}, title = {Spinal cord motor neuron phenotypes and polygenic risk scores in sporadic amyotrophic lateral sclerosis: deciphering the disease pathology and therapeutic potential of ropinirole hydrochloride.}, journal = {Journal of neurology, neurosurgery, and psychiatry}, volume = {96}, number = {2}, pages = {199-201}, pmid = {39231585}, issn = {1468-330X}, } @article {pmid39231554, year = {2024}, author = {Gong, Z and Deng, W and Li, Z and Tang, J and Zhang, M}, title = {Association between apathy and caregiver burden in patients with amyotrophic lateral sclerosis: a cross-sectional study.}, journal = {BMJ open}, volume = {14}, number = {9}, pages = {e080803}, pmid = {39231554}, issn = {2044-6055}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/psychology ; Male ; Female ; Cross-Sectional Studies ; *Apathy ; Middle Aged ; *Anxiety/psychology/etiology ; *Depression/psychology/etiology ; China/epidemiology ; *Caregiver Burden/psychology ; Aged ; Caregivers/psychology ; Adult ; Cognitive Dysfunction/etiology/psychology ; Psychiatric Status Rating Scales ; Logistic Models ; Cost of Illness ; }, abstract = {OBJECTIVES: To investigate the relationship among patients' apathy, cognitive impairment, depression, anxiety, and caregiver burden in amyotrophic lateral sclerosis (ALS).

DESIGN: A cross-sectional study design was used.

SETTING: The study was conducted at a tertiary hospital in Wuhan, Hubei, China.

PARTICIPANTS: A total of 109 patients with ALS and their caregivers were included.

OUTCOME MEASURES: Patients with ALS were screened using the Edinburgh Cognitive and Behavioural Screen, Beck Depression Inventory-II, Generalised Anxiety Disorder-7 and Apathy Scale to assess their cognition, depression, anxiety and apathy, respectively. The primary caregivers completed the Zarit Burden Interview. The association between apathy, cognitive impairment, depression, anxiety and caregiver burden was analysed using logistic regression. Mediation models were employed to investigate the mediating effect of patients' apathy on the relationship between depression/anxiety and caregiver burden.

RESULTS: Patients in the high caregiver burden group exhibited significantly higher levels of depression, anxiety and apathy compared with those in the low caregiver burden group (p<0.05). There was a positive association observed between caregiver burden and disease course (rs=0.198, p<0.05), depression (rs=0.189, p<0.05), anxiety (rs=0.257, p<0.05) and apathy (rs=0.388, p<0.05). There was a negative association between caregiver burden and the Revised ALS Functional Rating Scale (rs=-0.275, p<0.05). Apathy was an independent risk factor for higher caregiver burden (OR 1.121, 95% CI 1.041 to 1.206, p<0.05). Apathy fully mediated the relationship between depression and caregiver burden (β=0.35, 95% CI 0.16 to 0.54, p<0.05) while partially mediating the relationship between anxiety and caregiver burden (β=0.34, 95% CI 0.16 to 0.52, p<0.05).

CONCLUSIONS: Apathy, depression and anxiety exerted a detrimental impact on caregiver burden in individuals with ALS. Apathy played a mediating role in the relationship between depression and caregiver burden and between anxiety and caregiver burden. These findings underscore the importance of identifying apathy and developing interventions for its management within the context of ALS.}, } @article {pmid39231437, year = {2024}, author = {Chu, HS and Oh, J}, title = {Family Caregivers' Experiences of People With Amyotrophic Lateral Sclerosis Undergoing Gastrostomy Tube Feeding.}, journal = {The Journal of neuroscience nursing : journal of the American Association of Neuroscience Nurses}, volume = {56}, number = {6}, pages = {224-228}, pmid = {39231437}, issn = {1945-2810}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/nursing/psychology ; *Caregivers/psychology ; *Enteral Nutrition ; *Gastrostomy ; Female ; Male ; Middle Aged ; Republic of Korea ; *Qualitative Research ; Adult ; Aged ; Stress, Psychological ; Interviews as Topic ; }, abstract = {INTRODUCTION: In amyotrophic lateral sclerosis (ALS) patients with impaired swallowing function, gastrostomy tube (G-tube) placement is recommended, but significantly increases the caregiving burden on families. This study aimed to describe the experiences of family caregivers of patients with ALS receiving home enteral nutrition through a G-tube. METHOD: Using purposive sampling, 8 family caregivers participated in the study. Data collection was conducted between February 2021 and October 2022 at a university hospital in Seoul, Korea. Semistructured face-to-face interviews were used to collect data until saturation. Data were analyzed using Krippendorff's content analysis approach. RESULTS: Qualitative analysis of the data revealed 3 main themes regarding caregiving. The emerging themes included psychological distress, unmet practical needs, and the struggle to provide care. CONCLUSION: After a G-tube placement, family caregivers experience various emotional stresses and have numerous unmet practical needs. Healthcare professionals caring for people with ALS receiving enteral nutrition should provide a tailored support program that addresses the specific needs of these family caregivers.}, } @article {pmid39231048, year = {2024}, author = {Trescato, I and Tavazzi, E and Vettoretti, M and Gatta, R and Vasta, R and Chio, A and Camillo, BD}, title = {DYNAMITE: Integrating Archetypal Analysis and Process Mining for Interpretable Disease Progression Modelling.}, journal = {IEEE journal of biomedical and health informatics}, volume = {28}, number = {12}, pages = {7553-7564}, doi = {10.1109/JBHI.2024.3453602}, pmid = {39231048}, issn = {2168-2208}, mesh = {Humans ; *Disease Progression ; *Data Mining/methods ; Amyotrophic Lateral Sclerosis/physiopathology ; }, abstract = {DYNAMITE, an acronym for DYNamic Archetypal analysis for MIning disease TrajEctories, is a new methodology developed specifically to model disease progression by exploiting information available in longitudinal clinical datasets. First, archetypal analysis is applied to data organised in matrix form, with the aim of finding extreme and representative disease states (archetypes) linked to the original data through convex coefficients. Then, each original observation is associated with a single archetype based on their similarity; finally, an event log is created encoding the progression of disease states for each patient in terms of archetype states. In the last stage of the procedure, archetypal analysis is coupled with process mining, which allows the event log archetypes to be visualised graphically as sequences of disease states, allowing the clinical trajectories of patients to be extracted and examined. As a proof of concept, we applied the proposed method to data from a cohort of amyotrophic lateral sclerosis patients whose progression was monitored using the 12-item ALSFRS-R questionnaire. Without any a priori knowledge, DYNAMITE identified six archetypes clearly describing different types and severity of impairment and provided reliable clinical trajectories consistent with the prognosis of amyotrophic lateral sclerosis patients. DYNAMITE offers high interpretability at every stage of the analysis, which makes it particularly suitable for use in healthcare where explainability is paramount, and enables analysis of clinical trajectories at both individual and population levels.}, } @article {pmid39230722, year = {2024}, author = {Chalitsios, CV and Ley, H and Gao, J and Turner, MR and Thompson, AG}, title = {Apolipoproteins, lipids, lipid-lowering drugs and risk of amyotrophic lateral sclerosis and frontotemporal dementia: a meta-analysis and Mendelian randomisation study.}, journal = {Journal of neurology}, volume = {271}, number = {10}, pages = {6956-6969}, pmid = {39230722}, issn = {1432-1459}, support = {MR/T006927/1/MRC_/Medical Research Council/United Kingdom ; Thompson/Apr23/896-791/MNDA_/Motor Neurone Disease Association/United Kingdom ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/blood/genetics/epidemiology ; *Apolipoproteins/antagonists & inhibitors/blood/genetics ; *Frontotemporal Dementia/blood/genetics/epidemiology ; Hypolipidemic Agents/pharmacology/therapeutic use ; Lipids/blood ; Mendelian Randomization Analysis ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) have clinical, pathological and genetic overlapping. Lipid pathways are implicated in ALS. This study examined the effect of blood lipid levels on ALS, FTD risk, and survival in ALS.

METHODS: A systematic review and meta-analysis of high and low-density lipoprotein cholesterol (HDL-c and LDL-c), total cholesterol, triglycerides, apolipoproteins B and A1 levels with ALS was performed. Two-sample Mendelian randomisation (MR) analysis sought the causal effects of these exposures on ALS, FTD, and survival in ALS. The effect of lipid-lowering drugs was also examined using genetic proxies for targets of lipid-lowering medications.

RESULTS: Three cohort studies met the inclusion criteria for meta-analysis. Meta-analysis indicated an association between higher LDL-c (HRper mmol/L = 1.07, 95%CI:1.02-1.12; I 2 =18%) and lower HDL-c (HRper mmol/L = 0.83, 95%CI:0.74-0.94; I 2 =0%) with an increased risk of ALS. MR suggested causal effects of higher LDL-c (ORIVW = 1.085, 95%:CI 1.008-1.168, pFDR = 0.0406), total cholesterol (ORIVW = 1.081, 95%:CI 1.013-1.154, pFDR = 0.0458) and apolipoprotein B (ORIVW = 1.104, 95%:CI 1.041-1.171, pFDR = 0.0061) increasing ALS risk, and higher apolipoprotein B level increasing FTD risk (ORIVW = 1.424, 95%CI 1.072-1.829, pFDR = 0.0382). Reducing LDL-c through APOB inhibition was associated with lower ALS (ORIVW = 0.84, 95%CI 0.759-0.929, pFDR = 0.00275) and FTD risk (ORIVW = 0.581, 95%CI 0.387-0.874, pFDR = 0.0362).

CONCLUSION: These data support the influence of LDL-c and total cholesterol on ALS risk and apolipoprotein B on the risk of ALS and FTD. Potential APOB inhibition might decrease the risk of sporadic ALS and FTD. Further work in monogenic forms of ALS and FTD is necessary to determine whether blood lipids influence penetrance and phenotype.}, } @article {pmid39229489, year = {2024}, author = {Feng, F and Feng, G and Liu, J and Hao, W and Huang, W and Bi, X and Li, M and Wang, H and Yang, F and He, Z and Bai, J and Wang, H and Ma, G and Xu, B and Shu, N and Huang, X}, title = {Different patterns of structural network impairments in two amyotrophic lateral sclerosis subtypes driven by [18]F-fluorodeoxyglucose positron emission tomography/magnetic resonance hybrid imaging.}, journal = {Brain communications}, volume = {6}, number = {5}, pages = {fcae222}, pmid = {39229489}, issn = {2632-1297}, abstract = {The structural network damages in amyotrophic lateral sclerosis patients are evident but contradictory due to the high heterogeneity of the disease. We hypothesized that patterns of structural network impairments would be different in amyotrophic lateral sclerosis subtypes by a data-driven method using [18]F-fluorodeoxyglucose positron emission tomography/magnetic resonance hybrid imaging. The data of positron emission tomography, structural MRI and diffusion tensor imaging in fifty patients with amyotrophic lateral sclerosis and 23 healthy controls were collected by a [18]F-fluorodeoxyglucose positron emission tomography/magnetic resonance hybrid. Two amyotrophic lateral sclerosis subtypes were identified as the optimal cluster based on grey matter volume and standardized uptake value ratio. Network metrics at the global, local and connection levels were compared to explore the impaired patterns of structural networks in the identified subtypes. Compared with healthy controls, the two amyotrophic lateral sclerosis subtypes displayed a pattern of a locally impaired structural network centralized in the sensorimotor network and a pattern of an extensively impaired structural network in the whole brain. When comparing the two amyotrophic lateral sclerosis subgroups by a support vector machine classifier based on the decreases in nodal efficiency of structural network, the individualized network scores were obtained in every amyotrophic lateral sclerosis patient and demonstrated a positive correlation with disease severity. We clustered two amyotrophic lateral sclerosis subtypes by a data-driven method, which encompassed different patterns of structural network impairments. Our results imply that amyotrophic lateral sclerosis may possess the intrinsic damaged pattern of white matter network and thus provide a latent direction for stratification in clinical research.}, } @article {pmid39229486, year = {2024}, author = {Rivers-Auty, J and Hoyle, C and Pointer, A and Lawrence, C and Pickering-Brown, S and Brough, D and Ryan, S}, title = {C9orf72 dipeptides activate the NLRP3 inflammasome.}, journal = {Brain communications}, volume = {6}, number = {5}, pages = {fcae282}, pmid = {39229486}, issn = {2632-1297}, support = {/WT_/Wellcome Trust/United Kingdom ; }, abstract = {Frontotemporal dementia and amyotrophic lateral sclerosis are neurodegenerative diseases with considerable clinical, genetic and pathological overlap. The most common cause of both diseases is a hexanucleotide repeat expansion in C9orf72. The expansion is translated to produce five toxic dipeptides, which aggregate in patient brain. Neuroinflammation is a feature of frontotemporal dementia and amyotrophic lateral sclerosis; however, its causes are unknown. The nod-like receptor family, pyrin domain-containing 3 inflammasome is implicated in several other neurodegenerative diseases as a driver of damaging inflammation. The inflammasome is a multi-protein complex which forms in immune cells in response to tissue damage, pathogens or aggregating proteins. Inflammasome activation is observed in models of other neurodegenerative diseases such as Alzheimer's disease, and inflammasome inhibition rescues cognitive decline in rodent models of Alzheimer's disease. Here, we show that a dipeptide arising from the C9orf72 expansion, poly-glycine-arginine, activated the inflammasome in microglia and macrophages, leading to secretion of the pro-inflammatory cytokine, interleukin-1β. Poly-glycine-arginine also activated the inflammasome in organotypic hippocampal slice cultures, and immunofluorescence imaging demonstrated formation of inflammasome specks in response to poly-glycine-arginine. Several clinically available anti-inflammatory drugs rescued poly-glycine-arginine-induced inflammasome activation. These data suggest that C9orf72 dipeptides contribute to the neuroinflammation observed in patients, and highlight the inflammasome as a potential therapeutic target for frontotemporal dementia and amyotrophic lateral sclerosis.}, } @article {pmid39229047, year = {2024}, author = {Wairagkar, M and Card, NS and Singer-Clark, T and Hou, X and Iacobacci, C and Hochberg, LR and Brandman, DM and Stavisky, SD}, title = {An instantaneous voice synthesis neuroprosthesis.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {39229047}, issn = {2692-8205}, support = {DP2 DC021055/DC/NIDCD NIH HHS/United States ; U01 DC017844/DC/NIDCD NIH HHS/United States ; }, abstract = {Brain computer interfaces (BCIs) have the potential to restore communication to people who have lost the ability to speak due to neurological disease or injury. BCIs have been used to translate the neural correlates of attempted speech into text[1-3]. However, text communication fails to capture the nuances of human speech such as prosody, intonation and immediately hearing one's own voice. Here, we demonstrate a "brain-to-voice" neuroprosthesis that instantaneously synthesizes voice with closed-loop audio feedback by decoding neural activity from 256 microelectrodes implanted into the ventral precentral gyrus of a man with amyotrophic lateral sclerosis and severe dysarthria. We overcame the challenge of lacking ground-truth speech for training the neural decoder and were able to accurately synthesize his voice. Along with phonemic content, we were also able to decode paralinguistic features from intracortical activity, enabling the participant to modulate his BCI-synthesized voice in real-time to change intonation, emphasize words, and sing short melodies. These results demonstrate the feasibility of enabling people with paralysis to speak intelligibly and expressively through a BCI.}, } @article {pmid39229019, year = {2024}, author = {Erwin, AL and Chang, ML and Fernandez, MG and Attili, D and Russ, JE and Sutanto, R and Pinarbasi, ES and Bekier, M and Brant, TS and Hahn, T and Dykstra, M and Thomas, D and Li, X and Baldridge, RD and Tank, EMH and Barmada, SJ and Mosalaganti, S}, title = {Molecular Visualization of Neuronal TDP43 Pathology In Situ.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {39229019}, issn = {2692-8205}, support = {DP2 GM150019/GM/NIGMS NIH HHS/United States ; S10 OD030275/OD/NIH HHS/United States ; T32 GM007544/GM/NIGMS NIH HHS/United States ; P30 AG072931/AG/NIA NIH HHS/United States ; T32 GM141840/GM/NIGMS NIH HHS/United States ; R01 NS113943/NS/NINDS NIH HHS/United States ; R01 NS097542/NS/NINDS NIH HHS/United States ; R56 NS128110/NS/NINDS NIH HHS/United States ; F31 NS134123/NS/NINDS NIH HHS/United States ; R35 GM128592/GM/NIGMS NIH HHS/United States ; }, abstract = {Nuclear exclusion and cytoplasmic accumulation of the RNA-binding protein TDP43 are characteristic of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Despite this, the origin and ultrastructure of cytosolic TDP43 deposits remain unknown. Accumulating evidence suggests that abnormal RNA homeostasis can drive pathological TDP43 mislocalization, enhancing RNA misprocessing due to loss of nuclear TDP43 and engendering a cycle that ends in cell death. Here, we show that adding small monovalent oligonucleotides successfully recapitulates pathological TDP43 mislocalization and aggregation in iPSC-derived neurons (iNeurons). By employing a multimodal in situ cryo-correlative light and electron microscopy pipeline, we examine how RNA influences the localization and aggregation of TDP43 in near-native conditions. We find that mislocalized TDP43 forms ordered fibrils within lysosomes and autophagosomes in iNeurons as well as in patient tissue, and provide the first high-resolution snapshots of TDP43 aggregates in situ. In so doing, we provide a cellular model for studying initial pathogenic events underlying ALS, FTLD, and related TDP43-proteinopathies.}, } @article {pmid39227882, year = {2024}, author = {Zelina, P and de Ruiter, AA and Kolsteeg, C and van Ginneken, I and Vos, HR and Supiot, LF and Burgering, BMT and Meye, FJ and Veldink, JH and van den Berg, LH and Pasterkamp, RJ}, title = {ALS-associated C21ORF2 variant disrupts DNA damage repair, mitochondrial metabolism, neuronal excitability and NEK1 levels in human motor neurons.}, journal = {Acta neuropathologica communications}, volume = {12}, number = {1}, pages = {144}, pmid = {39227882}, issn = {2051-5960}, support = {TOTALS//Stichting ALS Nederland/ ; GoALS//Stichting ALS Nederland/ ; MAXOMOD//E-Rare/ ; TRIAGE//JPND/ ; X-omics initiative//Nederlandse Organisatie voor Wetenschappelijk Onderzoek/ ; EScORIAL//H2020 European Research Council/ ; }, mesh = {Animals ; Humans ; Mice ; *Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology ; DNA Damage ; DNA Repair/genetics ; *Induced Pluripotent Stem Cells/metabolism ; *Mitochondria/metabolism/pathology ; *Motor Neurons/metabolism/pathology ; Mutation ; *NIMA-Related Kinase 1/genetics/metabolism ; *Zebrafish ; Cytoskeletal Proteins/genetics/metabolism ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disease leading to motor neuron loss. Currently mutations in > 40 genes have been linked to ALS, but the contribution of many genes and genetic mutations to the ALS pathogenic process remains poorly understood. Therefore, we first performed comparative interactome analyses of five recently discovered ALS-associated proteins (C21ORF2, KIF5A, NEK1, TBK1, and TUBA4A) which highlighted many novel binding partners, and both unique and shared interactors. The analysis further identified C21ORF2 as a strongly connected protein. The role of C21ORF2 in neurons and in the nervous system, and of ALS-associated C21ORF2 variants is largely unknown. Therefore, we combined human iPSC-derived motor neurons with other models and different molecular cell biological approaches to characterize the potential pathogenic effects of C21ORF2 mutations in ALS. First, our data show C21ORF2 expression in ALS-relevant mouse and human neurons, such as spinal and cortical motor neurons. Further, the prominent ALS-associated variant C21ORF2-V58L caused increased apoptosis in mouse neurons and movement defects in zebrafish embryos. iPSC-derived motor neurons from C21ORF2-V58L-ALS patients, but not isogenic controls, show increased apoptosis, and changes in DNA damage response, mitochondria and neuronal excitability. In addition, C21ORF2-V58L induced post-transcriptional downregulation of NEK1, an ALS-associated protein implicated in apoptosis and DDR. In all, our study defines the pathogenic molecular and cellular effects of ALS-associated C21ORF2 mutations and implicates impaired post-transcriptional regulation of NEK1 downstream of mutant C21ORF72 in ALS.}, } @article {pmid39227337, year = {2024}, author = {Choi, SJ and Yoo, SH and Lee, SY and Sung, JJ}, title = {Withdrawal of Life-Sustaining Mechanical Ventilation for a Patient With Amyotrophic Lateral Sclerosis in Locked-In Syndrome.}, journal = {Journal of clinical neurology (Seoul, Korea)}, volume = {20}, number = {5}, pages = {537-538}, pmid = {39227337}, issn = {1738-6586}, support = {NRF-2018R1A5A2025964/NRF/National Research Foundation of Korea/Korea ; }, } @article {pmid39226927, year = {2024}, author = {Cossu, L and Cappon, G and Facchinetti, A}, title = {Adaptive and self-learning Bayesian filtering algorithm to statistically characterize and improve signal-to-noise ratio of heart-rate data in wearable devices.}, journal = {Journal of the Royal Society, Interface}, volume = {21}, number = {218}, pages = {20240222}, pmid = {39226927}, issn = {1742-5662}, support = {//Horizon 2020 Framework Programme/ ; }, mesh = {Humans ; *Bayes Theorem ; *Wearable Electronic Devices ; *Heart Rate/physiology ; *Algorithms ; *Signal-To-Noise Ratio ; Male ; Female ; Signal Processing, Computer-Assisted ; }, abstract = {The use of wearable sensors to monitor vital signs is increasingly important in assessing individual health. However, their accuracy often falls short of that of dedicated medical devices, limiting their usefulness in a clinical setting. This study introduces a new Bayesian filtering (BF) algorithm that is designed to learn the statistical characteristics of signal and noise, allowing for optimal smoothing. The algorithm is able to adapt to changes in the signal-to-noise ratio (SNR) over time, improving performance through windowed analysis and Bayesian criterion-based smoothing. By evaluating the algorithm on heart-rate (HR) data collected from Garmin Vivoactive 4 smartwatches worn by individuals with amyotrophic lateral sclerosis and multiple sclerosis, it is demonstrated that BF provides superior SNR tracking and smoothing compared with non-adaptive methods. The results show that BF accurately captures SNR variability, reducing the root mean square error from 2.84 bpm to 1.21 bpm and the mean absolute relative error from 3.46% to 1.36%. These findings highlight the potential of BF as a preprocessing tool to enhance signal quality from wearable sensors, particularly in HR data, thereby expanding their applications in clinical and research settings.}, } @article {pmid39226712, year = {2024}, author = {Santos Silva, C and Gormicho, M and Simão, S and Pronto-Laborinho, AC and Alves, I and Pinto, S and Oliveira Santos, M and de Carvalho, M}, title = {C9orf72 gene repeat expansion phenotype profile of motor neurone disease in Portugal.}, journal = {Journal of the neurological sciences}, volume = {465}, number = {}, pages = {123208}, doi = {10.1016/j.jns.2024.123208}, pmid = {39226712}, issn = {1878-5883}, mesh = {Humans ; Male ; Portugal/epidemiology ; Female ; Middle Aged ; *C9orf72 Protein/genetics ; *Motor Neuron Disease/genetics/epidemiology ; Aged ; *Phenotype ; *DNA Repeat Expansion/genetics ; Cohort Studies ; Amyotrophic Lateral Sclerosis/genetics/diagnosis ; }, abstract = {BACKGROUND: C9orf72 gene repeat expansion (C9RE) is the most frequent gene variant associated with amyotrophic lateral sclerosis (ALS). We aimed to study the phenotype of motor neurone disease (MND) patients with C9RE in a Portuguese cohort.

METHODS: Demographical and clinical data of MND patients with (C9RE+) and without C9RE were compared. ALS al Rating Scale-Revised (ALSFRS-R) and Edinburgh Cognitive and Behavioural ALS Screen (ECAS) were used to evaluate functional and cognitive performance, respectively. Survival analysis was performed using Kaplan Meier log-rank test and Cox proportional hazards model.

RESULTS: We included 761 patients of whom 61 (8.0 %) were C9RE+. C9RE+ patients had a higher frequency of ALS (95.1 vs 78.4 %, p = 0.002), and lower frequency of progressive muscular atrophy (3.3 vs 16.7 %, p = 0.006). C9RE+ was associated with earlier age of onset (58.1 vs 62.6 years, p = 0.003) and more frequent MND family history (65.5 vs 11.4 %, p < 0.001). Gender, ethnicity, onset site, diagnostic delay, disease progression rate until diagnosis (ΔF), ALSFRS-R and time until non-invasive ventilation did not differ between groups. Cognitive/behavioural symptoms and ECAS did not differ between groups, except a worse visuospatial score in C9RE+ group (p = 0.035). Death rate was 1.8 and 1.6 times higher in C9RE+ patients with MND and ALS, respectively. Significant survival prognostic factors in C9RE+ group were diagnosis delay (HR = 0.96, 95 %CI 0.92-0.99, p = 0.008) and ΔF (HR = 1.93, 95 %CI 1.26-2.96, p = 0.002).

CONCLUSION: Our study corroborates most previous cohorts' findings, but harbours some singularities regarding onset site, phenotype, and cognitive profile, that contribute to a better understanding of C9RE epidemiology.}, } @article {pmid39226692, year = {2024}, author = {Kwon, S and Kim, B and Han, KD and Jung, W and Cho, EB and Shin, DW and Min, JH}, title = {Risk of depression in amyotrophic lateral sclerosis: A nationwide cohort study in South Korea.}, journal = {Journal of psychiatric research}, volume = {178}, number = {}, pages = {414-420}, doi = {10.1016/j.jpsychires.2024.08.030}, pmid = {39226692}, issn = {1879-1379}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/epidemiology ; Republic of Korea/epidemiology ; Male ; Female ; Middle Aged ; Aged ; *Depression/epidemiology ; Adult ; Cohort Studies ; Proportional Hazards Models ; }, abstract = {Depression is frequently reported in amyotrophic lateral sclerosis (ALS) due to the disastrous prognosis of progressive motor impairment, but the risk of depression in ALS is still unclear. Therefore, we investigated the risk of depression in ALS and analyzed the effect of ALS-related physical disability on the risk of developing depression using the Korean National Health Insurance Service (KNHIS) database. A total of 2241 ALS patients, as defined by the International Classification Diseases (ICD, G12.21) and Rare Intractable Disease codes (V123), and 1:10 sex- and age-matched controls were selected from the KNHIS. After applying exclusion criteria (non-participation in national health screening, history of depression, or having missing data), 595 ALS patients and 9896 non-ALS individuals were finally selected. Primary outcome is newly diagnosed depression during follow-up duration defined by ICD code (F32 or F33). A Cox regression model was used to examine the hazard ratios (HRs) after adjustment for potential confounders. During the follow-up period, 283 cases of depression in the ALS group and 1547 in the controls were recorded. The adjusted HR for depression in ALS was 9.1 (95% confidence interval [CI] 7.87-10.60). The risk of depression was slightly higher in the disabled ALS group (aHR 10.1, 95% CI 7.98-12.67) than in the non-disabled ALS group (aHR 8.78, 95% CI 7.42-10.39). The relative risk of depression was higher in younger patients than in older patients, and in obese patients than in non-obese patients. Our study showed that ALS patients have an increased risk of depression compared to non-ALS individuals.}, } @article {pmid39225243, year = {2024}, author = {Liang, J and Zhu, Y and Liu, S and Kuang, B and Tian, Z and Zhang, L and Yang, S and Lin, M and Chen, N and Liu, X and Ai, Q and Yang, Y}, title = {Progress of Exosomal MicroRNAs and Traditional Chinese Medicine Monomers in Neurodegenerative Diseases.}, journal = {Phytotherapy research : PTR}, volume = {38}, number = {11}, pages = {5323-5349}, doi = {10.1002/ptr.8322}, pmid = {39225243}, issn = {1099-1573}, support = {//The Key Discipline of Biological Engineering of Hunan University of Chinese Medicine [2018] No. 3/ ; 22JBZ052//Hunan University of Chinese Medicine Discipline Construction Project/ ; 202329-2//Key Project of Changsha Hospital for Maternal & Child Health Care Affiliated to Hunan Normal University/ ; 2021JJ30512//Hunan Natural Science Foundation/ ; 2022JJ40313//Hunan Natural Science Foundation/ ; 2022JJ40456//Hunan Natural Science Foundation/ ; 2023JJ60126//Hunan Natural Science Foundation/ ; 2023JJ60471//Hunan Natural Science Foundation/ ; 21B0354//Outstanding Youth Project of Hunan Education Department/ ; B2023061//Scientific Research Project of Hunan Provincial Administration of Traditional Chinese Medicine/ ; //Hunan University of Chinese Medicine First-class Disciple Construction Project of Chinese Material Medica/ ; kq2014091//Changsha Natural Science Foundation/ ; kq2202269//Changsha Natural Science Foundation/ ; //The First-class Discipline Construction Project of Chemical Engineering and Technology of Hunan University of Traditional Chinese Medicine/ ; 212010//Special Scientific and Technological Project for Comprehensive Utilization of Ampelopsis grossedentata Resources of Hunan Qiankun Biotechnology Co., Ltd/ ; 2019xjjj001//Key Project of Hunan University of Chinese Medicine School level Scientific Research Fund/ ; 2021XJJJ028//Key Project of Hunan University of Chinese Medicine School level Scientific Research Fund/ ; U2202214//National Natural Science Foundation of China/ ; }, mesh = {Humans ; *Exosomes/metabolism ; *MicroRNAs/genetics ; *Neurodegenerative Diseases/drug therapy ; *Medicine, Chinese Traditional/methods ; Drugs, Chinese Herbal/pharmacology ; Animals ; }, abstract = {Exosomes, extracellular vesicles secreted by various cells, actively participate in intercellular communication by facilitating the exchange of crucial molecular information such as DNA, RNA, and lipids. Within this intricate network, microRNAs, endogenous non-coding small RNAs, emerge as pivotal regulators of post-transcriptional gene expression, significantly influencing the development of neurodegenerative diseases. The historical prominence of traditional Chinese medicine (TCM) in clinical practice in China underscores its enduring significance. Notably, TCM monomers, serving as active constituents within herbal medicine, assume a critical role in the treatment of neurodegenerative diseases, particularly in mitigating oxidative stress, inhibiting apoptosis, and reducing inflammation. This comprehensive review aims to delineate the specific involvement of exosomal microRNAs in various neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, Huntington's disease, stroke, and amyotrophic lateral sclerosis. Furthermore, the exploration extends to the application of TCM monomers, elucidating their efficacy as therapeutic agents in these conditions. Additionally, the review examines the utilization of exosomes as drug delivery carriers in the context of neurodegenerative diseases, providing a nuanced understanding of the potential synergies between TCM and modern therapeutic approaches. This synthesis of knowledge aims to contribute to the advancement of our comprehension of the intricate molecular mechanisms underlying neurodegeneration and the potential therapeutic avenues offered by TCcom interventions.}, } @article {pmid39225106, year = {2024}, author = {Białobrodzka, E and Flis, DJ and Akdogan, B and Borkowska, A and Wieckowski, MR and Antosiewicz, J and Zischka, H and Dzik, KP and Kaczor, JJ and Ziolkowski, W}, title = {Amyotrophic Lateral Sclerosis and swim training affect copper metabolism in skeletal muscle in a mouse model of disease.}, journal = {Muscle & nerve}, volume = {70}, number = {5}, pages = {1111-1118}, doi = {10.1002/mus.28237}, pmid = {39225106}, issn = {1097-4598}, support = {//Narodowe Centrum Nauki/ ; DEC-2013/09/NZ7/02538//National Science Centre/ ; 2020/39/B/NZ7/03366//National Science Centre/ ; }, mesh = {Animals ; *Amyotrophic Lateral Sclerosis/metabolism ; *Muscle, Skeletal/metabolism ; Mice ; *Copper/metabolism ; *Disease Models, Animal ; *Mice, Transgenic ; *Swimming ; Superoxide Dismutase/metabolism ; Copper-Transporting ATPases/metabolism/genetics ; Physical Conditioning, Animal/physiology ; Superoxide Dismutase-1/metabolism/genetics ; Adenosine Triphosphatases/metabolism ; Cation Transport Proteins/metabolism ; Male ; Copper Transporter 1/metabolism ; }, abstract = {INTRODUCTION/AIMS: Swim training and regulation of copper metabolism result in clinical benefits in amyotrophic lateral sclerosis (ALS) mice. Therefore, the study aimed to determine whether swim training improves copper metabolism by modifying copper metabolism in the skeletal muscles of ALS mice.

METHODS: SOD1G93A mice (n = 6 per group) were used as the ALS model, and wild-type B6SJL (WT) mice as controls (n = 6). Mice with ALS were analyzed before the onset of ALS (ALS BEFORE), at baseline ALS (first disease symptoms, trained and untrained, ALS ONSET), and at the end of ALS (last stage disease, trained and untrained, ALS TERMINAL). Copper concentrations and the level of copper metabolism proteins in the skeletal muscles of the lower leg were determined.

RESULTS: ALS disease caused a reduction in the copper concentration in ALS TERMINAL untrained mice compared with the ALS BEFORE (10.43 ± 1.81 and 38.67 ± 11.50 μg/mg, respectively, p = .0213). The copper chaperon for SOD1 protein, which supplies copper to SOD1, and ATPase7a protein (copper exporter), increased at the terminal stage of disease by 57% (p = .0021) and 34% (p = .0372), while the CTR1 protein (copper importer) decreased by 45% (p = .002). Swim training moderately affected the copper concentration and the concentrations of proteins responsible for copper metabolism in skeletal muscles.

DISCUSSION: The results show disturbances in skeletal muscle copper metabolism associated with ALS progression, which is moderately affected by swim training. From a clinical point of view, exercise in water for ALS patients should be an essential element of rehabilitation for maintaining quality of life.}, } @article {pmid39224919, year = {2024}, author = {Kiernan, MC and Kaji, R}, title = {Emerging concepts and therapies for amyotrophic lateral sclerosis.}, journal = {Current opinion in neurology}, volume = {37}, number = {5}, pages = {558-559}, doi = {10.1097/WCO.0000000000001308}, pmid = {39224919}, issn = {1473-6551}, mesh = {*Amyotrophic Lateral Sclerosis/therapy ; Humans ; }, } @article {pmid39224887, year = {2024}, author = {Yang, J and Tian, M and Zhang, L and Xin, C and Huo, J and Liu, Q and Dong, H and Li, R and Liu, Y}, title = {Assessment of Rab geranylgeranyltransferase subunit beta in amyotrophic lateral sclerosis.}, journal = {Frontiers in neurology}, volume = {15}, number = {}, pages = {1447461}, pmid = {39224887}, issn = {1664-2295}, abstract = {INTRODUCTION: Geranylgeranyltransferase Subunit Beta (RABGGTB) was expressed at higher levels in patients with Amyotrophic lateral sclerosis (ALS) compared with healthy controls. This study aims to observe the expression of RABGGTB in different cells from patients with ALS and different diseases.

METHODS: In this case-control study, we collected peripheral blood from patients with ALS and healthy controls, and compared the expression of RABGGTB in natural killer cells (NK), T cells and B cells between patients with ALS and healthy controls by flow cytometry. And compared the expression of RABGGTB in monocytes and monocyte-derived macrophages from patients with ALS, Parkinson's disease (PD), acute cerebrovascular disease (ACVD), and healthy controls by flow cytometry and immunofluorescence. Then flow cytometry was used to detect the expression of RABGGTB in monocytes from SOD1G93A mice and WT mice.

RESULTS: The expression of RABGGTB was not significantly changed in NK cells, cytotoxic T cells (CTL), helper T cells (Th), regulatory T cells (Treg), and B cells from patients with ALS compared to healthy controls. And the expression of RABGGTB in monocytes and monocyte-derived macrophages was higher in the ALS group than in the PD, ACVD and control group. The expression of RABGGTB was significantly higher in monocytes of SOD1G93A mice compared to WT mice.

CONCLUSION: These findings suggest that RABGGTB expression was increased in monocytes and monocyte-derived macrophages from patients with ALS, not in NK, CTL, Th, Treg, and B cells. Future studies are needed to find the clinical implication of RABGGTB in ALS.}, } @article {pmid39223525, year = {2024}, author = {Iakovleva, V and Verde, F and Cinnante, C and Sillani, A and Conte, G and Corsini, E and Ciusani, E and Erbetta, A and Silani, V and Ticozzi, N}, title = {Duropathy as a rare motor neuron disease mimic: from bibrachial amyotrophy to infratentorial superficial siderosis.}, journal = {BMC neurology}, volume = {24}, number = {1}, pages = {309}, pmid = {39223525}, issn = {1471-2377}, support = {PNC-E3-2022-23683266//Italian Ministry of Education and Research (MUR)/ ; }, mesh = {Humans ; Male ; Middle Aged ; *Motor Neuron Disease/diagnosis/complications/diagnostic imaging ; *Siderosis/complications/diagnosis/diagnostic imaging ; Magnetic Resonance Imaging/methods ; Diagnosis, Differential ; Dura Mater/diagnostic imaging/pathology ; }, abstract = {BACKGROUND: Bibrachial amyotrophy associated with an extradural CSF collection and infratentorial superficial siderosis (SS) are rare conditions that may occasionally mimic ALS. Both disorders are assumed to be due to dural tears.

CASE PRESENTATION: A 53-year-old man presented with a 7-year history of slowly progressive asymmetric bibrachial amyotrophy. Initially, a diagnosis of atypical motor neuron disease (MND) was made. At re-evaluation 11 years later, upper limb wasting and weakness had further progressed and were accompanied by sensorineural hearing loss. MRI of the brain and spine demonstrated extensive supra- and infratentorial SS (including the surface of the whole spinal cord) as well as a ventral longitudinal intraspinal fluid collection (VLISFC) extending along almost the entire thoracic spine. Osteodegenerative changes were observed at C5-C7 level, with osteophytes protruding posteriorly. The bony spurs at C6-C7 level were hypothesized to have lesioned the dura, causing a CSF leak and thus a VLISFC. Review of the MRI acquired at first evaluation showed that the VLISFC was already present at that time (actually beginning at C7 level), whereas the SS was not. 19 years after the onset of upper limb weakness, the patient additionally developed parkinsonism. Response to levodopa, brain scintigraphy with [123]I-ioflupane and brain MRI with nigrosome 1 evaluation were consistent with idiopathic Parkinson's disease (PD). On the latest follow-up 21 years after symptom onset, the VLISFC was unchanged, as were upper arm weakness and wasting.

CONCLUSIONS: Based on the long-term follow-up, we could establish that, while the evidence of the VLISFC was concomitant with the clinical presentation of upper limb amyotrophy and weakness, the radiological signs of SS appeared later. This suggests that SS was not per se the cause of the ALS-like clinical picture, but rather a long-term sequela of a dural leak. The latter was instead the causative lesion, giving rise to a VLISFC which compressed the cervical motor roots. Dural tears can actually cause several symptoms, and further studies are needed to elucidate the pathophysiological correlates of "duropathies". Finally, as iron metabolism has been implicated in PD, the co-occurrence of PD with SS deserves further investigation.}, } @article {pmid39222049, year = {2024}, author = {Santangelo, S and Invernizzi, S and Sorce, MN and Casiraghi, V and Peverelli, S and Brusati, A and Colombrita, C and Ticozzi, N and Silani, V and Bossolasco, P and Ratti, A}, title = {NEK1 haploinsufficiency worsens DNA damage, but not defective ciliogenesis, in C9ORF72 patient-derived iPSC-motoneurons.}, journal = {Human molecular genetics}, volume = {33}, number = {21}, pages = {1900-1907}, pmid = {39222049}, issn = {1460-2083}, support = {GR-2016-02364373//BIBLIOSAN/ ; PSR 2021//Italian Ministery of Health/ ; }, mesh = {*Induced Pluripotent Stem Cells/metabolism ; Humans ; *NIMA-Related Kinase 1/genetics ; *DNA Damage/genetics ; *Amyotrophic Lateral Sclerosis/genetics/pathology ; *C9orf72 Protein/genetics/metabolism ; *Haploinsufficiency/genetics ; *Motor Neurons/metabolism/pathology ; *Frontotemporal Dementia/genetics/pathology ; *Cilia/genetics/pathology/metabolism ; Cell Differentiation/genetics ; DNA Repeat Expansion/genetics ; Mutation ; }, abstract = {The hexanucleotide G4C2 repeat expansion (HRE) in C9ORF72 gene is the major cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), leading to both loss- and gain-of-function pathomechanisms. The wide clinical heterogeneity among C9ORF72 patients suggests potential modifying genetic and epigenetic factors. Notably, C9ORF72 HRE often co-occurs with other rare variants in ALS/FTD-associated genes, such as NEK1, which encodes for a kinase involved in multiple cell pathways, including DNA damage response and ciliogenesis. In this study, we generated induced pluripotent stem cells (iPSCs) and differentiated motoneurons (iPSC-MNs) from an ALS patient carrying both C9ORF72 HRE and a NEK1 loss-of-function mutation to investigate the biological effect of NEK1 haploinsufficiency on C9ORF72 pathology in a condition of oligogenicity. Double mutant C9ORF72/NEK1 cells showed increased pathological C9ORF72 RNA foci in iPSCs and higher DNA damage levels in iPSC-MNs compared to single mutant C9ORF72 cells, but no effect on DNA damage response. When we analysed the primary cilium, we observed a defective ciliogenesis in C9ORF72 iPSC-MNs which was not worsened by NEK1 haploinsufficiency in the double mutant iPSC-MNs. Altogether, our study shows that NEK1 haploinsufficiency influences differently DNA damage and cilia length, potentially acting as a modifier at biological level in an in vitro ALS patient-derived disease model of C9ORF72 pathology.}, } @article {pmid39218769, year = {2024}, author = {Sun, J and Zhang, Y}, title = {Microbiome and micronutrient in ALS: From novel mechanisms to new treatments.}, journal = {Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics}, volume = {21}, number = {6}, pages = {e00441}, pmid = {39218769}, issn = {1878-7479}, support = {I01 BX004824/BX/BLRD VA/United States ; R01 DK114126/DK/NIDDK NIH HHS/United States ; R01 DK134343/DK/NIDDK NIH HHS/United States ; }, mesh = {*Amyotrophic Lateral Sclerosis/microbiology/metabolism/therapy ; Humans ; *Micronutrients/metabolism ; *Gastrointestinal Microbiome/physiology ; Animals ; Dysbiosis ; Microbiota/physiology ; }, abstract = {Amyotrophic lateral sclerosis is a neurodegenerative disorder. Despite extensive studies, it remains challenging to treat ALS. Recent ALS studies have shown dysbiosis (e.g., loss of microbial diversity and beneficial function in the gut microbiota) is correlated with intestinal inflammation and change of intestinal integrity in ALS. The novel concepts and the roles of microbiome and microbial metabolites through the gut-microbiome-neuron axis in ALS pathogenesis have been slowly recognized by the neurology research field. Here, we will discuss the recent progress of microbiome, including bacteria, fungi, and viruses, in the ALS research. We will discuss our understanding of microbial metabolites in ALS. Micronutrition refers to the intake of essential vitamins, minerals, and other micronutrients. We will summarize the literation related to micronutrition and ALS. Furthermore, we will consider the mutual interactions of microbiome and micronutrition in the ALS progression and treatment. We further propose that the mechanistic and translational studies that shift from suspension of disbelief to cogent ingenuity, and from bench study to bed-side application, should allow new strategies of diagnosis and treatment for ALS.}, } @article {pmid39218293, year = {2024}, author = {Dibaj, P and Safavi-Abbasi, S and Asadollahi, E}, title = {In vivo spectrally unmixed multi-photon imaging of longitudinal axon-glia changes in injured spinal white matter.}, journal = {Neuroscience letters}, volume = {841}, number = {}, pages = {137959}, doi = {10.1016/j.neulet.2024.137959}, pmid = {39218293}, issn = {1872-7972}, mesh = {Animals ; *White Matter/pathology/metabolism/diagnostic imaging ; *Spinal Cord Injuries/pathology/metabolism/diagnostic imaging ; *Axons/pathology/metabolism ; *Mice, Transgenic ; Neuroglia/metabolism/pathology ; Mice ; Microscopy, Fluorescence, Multiphoton/methods ; Spinal Cord/pathology/metabolism ; Microglia/metabolism/pathology ; Astrocytes/metabolism/pathology ; }, abstract = {Understanding the sequence of cellular responses and their contributions to pathomorphogical changes in spinal white matter injuries is a prerequisite for developing efficient therapeutic strategies for spinal cord injury (SCI) as well as neurodegenerative and inflammatory diseases of the spinal cord such as amyotrophic lateral sclerosis and multiple sclerosis. We have developed several types of surgical procedures suitable for acute one-time and chronic recurrent in vivo multiphoton microscopy of spinal white matter [1]. Sophisticated surgical procedures were combined with transgenic mouse technology to image spinal tissue labeled with up to four fluorescent proteins (FPs) in axons, astrocytes, microglia, and blood vessels. To clearly separate the simultaneously excited FPs, spectral unmixing including iterative procedures was performed after imaging the diversely labeled spinal white matter with a custom-made 4-channel two-photon laser-scanning microscope. In our longitudinal multicellular studies of injured spinal white matter, we imaged axonal dynamics and invasion of microglia and astrocytes for a time course of over 200 days after SCI. Our methods offer ideal platforms for investigating acute and chronic cellular dynamics, cell-cell interactions, and metabolite fluctuations in health and disease as well as pharmacological manipulations in vivo.}, } @article {pmid39218010, year = {2024}, author = {Shojaie, A and Al Khleifat, A and Garrahy, S and Habash-Bailey, H and Thomson, R and Opie-Martin, S and Javidnia, S and Leigh, PN and Al-Chalabi, A}, title = {Investigating the impact of socioeconomic status on amyotrophic lateral sclerosis.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {25}, number = {7-8}, pages = {702-707}, pmid = {39218010}, issn = {2167-9223}, support = {/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/epidemiology/economics ; Male ; Female ; Middle Aged ; *Social Class ; Aged ; Adult ; Age of Onset ; Risk Factors ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the gradual death of motor neurons in the brain and spinal cord, leading to fatal paralysis. Socioeconomic status (SES) is a measure of an individual's shared economic and social status, which has been shown to have an association with health outcomes. Understanding the impact of SES on health conditions is crucial, as it can influence and be influenced by health-related variables. The role of socioeconomic status in influencing the risk and progression of ALS has not been established, and understanding the various factors that impact ALS is important in developing strategies for treatment and prevention. To investigate this relationship, we recruited 413 participants with definite, probable, or possible ALS according to the El Escorial criteria, from three tertiary centers in London, Sheffield, and Birmingham. Logistic regression was used to examine the association between case-control status, socioeconomic criteria, and ALS risk. Linear regression was used to examine the association between age of onset and socioeconomic variables. Two sensitivity analyses were performed, one using an alternative occupational classifier, and the other using Mendelian Randomization analysis to examine association. There was no significant relationship between any variables and ALS risk. We found an inverse relationship between mean lifetime salary and age of ALS onset (Beta = -0.157, p = 0.011), but no effect of education or occupation on the age of onset. The finding was confirmed in both sensitivity analyses and in Mendelian Randomization. We find that a higher salary is associated with a younger age of ALS onset taking into account sex, occupation, years of education, and clinical presentation.}, } @article {pmid39217855, year = {2024}, author = {Zhang, J and Chen, K and Chen, Y and Hua, L and Chen, S and Chen, X and Zou, L and Li, S and Yang, X and Shen, Y}, title = {Pathology reduction and motor behavior improvement associated with ultrasound-mediated delivery of arctiin to the motor cortex in a mutant SOD1 mouse model of amyotrophic lateral sclerosis.}, journal = {Ultrasonics}, volume = {144}, number = {}, pages = {107449}, doi = {10.1016/j.ultras.2024.107449}, pmid = {39217855}, issn = {1874-9968}, mesh = {Animals ; Male ; Mice ; *Amyotrophic Lateral Sclerosis ; *Disease Models, Animal ; Drug Delivery Systems ; Furans/pharmacology/administration & dosage ; Glucosides/pharmacology/administration & dosage ; *Mice, Transgenic ; Microbubbles ; *Motor Cortex/drug effects/physiopathology ; Mutation ; Superoxide Dismutase-1/genetics ; Ultrasonic Therapy/methods ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is marked by the deterioration of both cortical and spinal cord motor neurons. Despite the underlying causes of the disease remain elusive, there has been a growing attention on the well-being of cortical motor neurons in recent times. Focused ultrasound combined with microbubbles (FUS/MB) for opening the blood-brain barrier (BBB) provides a means for drug delivery to specific brain regions, holding significant promise for the treatment of neurological disorders.

OBJECTIVES: We aim to explore the outcomes of FUS/MB-mediated delivery of arctiin (Arc), a natural compound with anti-inflammatory activities, to the cerebral motor cortex area by using a transgenic ALS mouse model.

METHODS: The ALS mouse model with the SOD1[G93A] mutation was used and subjected to daily Arc administration with FUS/MB treatment twice a week. After six-week treatments, the motor performance was assessed by grip strength, wire hanging, and climbing-pole tests. Mouse brains, spinal cords and gastrocnemius muscle were harvested for histological staining.

RESULTS: Compared with the mice given Arc administration only, the combined treatments of FUS/MB with Arc induced further mitigation of the motor function decline, accompanied by improved health of the gastrocnemius muscle. Furthermore, notable neuroprotective effect was evidenced by the amelioration of motor neuron failure in the cortex and lumbar spinal cord.

CONCLUSION: These preliminary results indicated that the combined treatment of FUS/MB and arctiin exerted a potentially beneficial effect on neuromuscular function in the ALS disease.}, } @article {pmid39217293, year = {2024}, author = {Aljthalin, R and Albalawi, R and Alyahya, A and Alhathlool, R and Alhashemi, M}, title = {Multiple sclerosis and amyotrophic lateral sclerosis: is there an association or a red flag? A case report and literature review.}, journal = {BMC neurology}, volume = {24}, number = {1}, pages = {307}, pmid = {39217293}, issn = {1471-2377}, mesh = {Humans ; Female ; *Amyotrophic Lateral Sclerosis/diagnosis/complications/pathology ; Middle Aged ; *Multiple Sclerosis/complications/diagnosis/pathology ; Magnetic Resonance Imaging ; }, abstract = {BACKGROUND: Multiple sclerosis (MS) is an inflammatory disease of the central nervous system that causes damage to the myelin and axons and is caused by genetic or environmental factors. Amyotrophic lateral sclerosis (ALS) is characterized by rapidly progressive degeneration of the motor neurons resulting in the presence of upper and lower motor-neuron signs and symptoms.

CASE PRESENTATION: A 46-year-old female patient presented with symmetrical weakness of the lower limbs and numbness that developed over weeks. Magnetic resonance imaging (MRI) of the brain exhibited typical demyelination features, high signal abnormality involving the periventricular and subcortical white matter, and an oval-shaped lesion. The patient was diagnosed with MS based on the clinical presentation and radiological examination. However, there was rapid progression of the symptoms, involvement of bulbar dysfunction, and muscle atrophy. Furthermore, the patient did not respond to acute therapy and immunotherapy, which made the diagnosis of MS less likely or suggested that it could be associated with another diagnosis. Her neurophysiological test met the criteria of ALS, and she was started on riluzole.

LITERATURE REVIEW: We reviewed all articles from 1986 to 2023, and there were 32 reported cases describing the co-occurrence of ALS and MS in different populations. Our case is the 33rd, and to our knowledge, it is the only case reported in the Middle East and specifically in Saudi Arabia. The main proposed mechanism according to postmortem examinations is a combination of degenerative and inflammatory processes with a cascade of production of reactive oxygen species and nitric oxide, which lead to cell death and apoptosis during concomitant ALS with MS.

CONCLUSION: The co-occurrence of ALS and MS is extremely rare, but it can be explained by pathogenesis related to neurodegeneration, inflammation, or genetic susceptibility. Rapid progressive motor and bulbar symptoms could be red-flag symptoms, extensive evaluation might be needed for these patients.}, } @article {pmid39216161, year = {2024}, author = {Wang, J and Qi, J and Ouyang, Y and Zhou, S and Qin, L and Zhang, B and Bai, L and Pan, L}, title = {The mutation Asp-376-Glu in the ALS gene confers resistance to mesosulfuron-methyl in Beckmannia syzigachne.}, journal = {Plant physiology and biochemistry : PPB}, volume = {215}, number = {}, pages = {109083}, doi = {10.1016/j.plaphy.2024.109083}, pmid = {39216161}, issn = {1873-2690}, mesh = {*Acetolactate Synthase/genetics/metabolism ; *Herbicide Resistance/genetics ; *Herbicides/pharmacology ; *Sulfonylurea Compounds/pharmacology ; *Mutation ; Plant Proteins/genetics/metabolism ; Poaceae/genetics/drug effects ; Molecular Docking Simulation ; Plant Weeds/genetics/drug effects ; }, abstract = {Understanding the mechanisms by which weeds develop herbicide resistance is crucial for managing resistance effectively and optimizing herbicide use. Beckmannia syzigachne, a harmful grass weed prevalent in wheat and rice-wheat rotation areas, poses a significant threat to crop productivity. A field herbicide resistance survey identified a resistant population with a new ALS mutation (Asp-376-Glu). The Glu-376-Asp population displayed varying resistance levels to seven ALS herbicides, verified using the dCAPS method. qRT-PCR analysis showed that no significant difference existed in the ALS gene expression between the Asp-376-Glu and S populations. P450 and GST inhibitors failed to reverse resistance to mesosulfuron-methyl, suggesting no involvement of P450- and GST-based metabolic resistance. Molecular docking indicated that the Asp-376-Glu mutation reduces the binding affinity between ALS-inhibitors and BsALS. The findings provide valuable insights into herbicide resistance mechanisms for weed resistance control.}, } @article {pmid39216080, year = {2024}, author = {Mazurie, Z and Branchereau, P and Cattaert, D and Henkous, N and Savona-Baron, C and Vouimba, RM}, title = {Acute stress differently modulates interneurons excitability and synaptic plasticity in the primary motor cortex of wild-type and SOD1[G93A] mouse model of ALS.}, journal = {The Journal of physiology}, volume = {602}, number = {19}, pages = {4987-5015}, doi = {10.1113/JP285210}, pmid = {39216080}, issn = {1469-7793}, support = {GPR BRAIN-2030//Université de Bordeaux (University of Bordeaux)/ ; }, mesh = {Animals ; *Amyotrophic Lateral Sclerosis/physiopathology/genetics ; *Interneurons/physiology ; *Neuronal Plasticity ; *Motor Cortex/physiopathology ; Mice ; Male ; *Mice, Transgenic ; Disease Models, Animal ; Stress, Psychological/physiopathology ; Superoxide Dismutase-1/genetics ; Mice, Inbred C57BL ; }, abstract = {Primary motor cortex (M1) network stability depends on activity of inhibitory interneurons, for which susceptibility to stress was previously demonstrated in limbic regions. Hyperexcitability in M1 following changes in the excitatory/inhibitory balance is a key pathological hallmark of amyotrophic lateral sclerosis (ALS). Using electrophysiological approaches, we assessed the impact of acute restraint stress on inhibitory interneurons excitability and global synaptic plasticity in M1 of the SOD1[G93A] ALS mouse model at a late pre-symptomatic stage (10-12.5 weeks). Based on their firing type (continuous, discontinuous, with accommodation or not) and electrophysiological characteristics (resting potential, rheobase, firing frequency), interneurons from M1 slices were separated into four clusters, labelled from 1 to 4. Among them, only interneurons from the first cluster, presenting continuous firing with few accommodations, tended to show increased excitability in wild-type (WT) and decreased excitability in SOD1[G93A] animals following stress. In vivo analyses of evoked field potentials showed that stress suppressed the theta burst-induced plasticity of an excitatory component (N1) recorded in the superficial layers of M1 in WT, with no impact on an inhibitory complex (N2-P1) from the deeper layers. In SOD1[G93A] mice, stress did not affect N1 but suppressed the N2-P1 plasticity. These data suggest that stress can alter M1 network functioning in a different manner in WT and SOD1[G93A] mice, possibly through changes of inhibitory interneurons excitability and synaptic plasticity. This suggests that stress-induced activity changes in M1 may therefore influence ALS outcomes. KEY POINTS: Disruption of the excitatory/inhibitory balance in the primary motor cortex (M1) has been linked to cortical hyperexcitability development, a key pathological hallmark of amyotrophic lateral sclerosis (ALS). Psychological stress was reported to influence excitatory/inhibitory balance in limbic regions, but very little is known about its influence on the M1 functioning under physiological or pathological conditions. Our study revealed that acute stress influences the excitatory/inhibitory balance within the M1, through changes in interneurons excitability along with network plasticity. Such changes were different in pathological (SOD1[G93A] ALS mouse model) vs. physiological (wild-type) conditions. The results of our study help us to better understand how stress modulates the M1 and highlight the need to further characterize stress-induced motor cortex changes because it may be of importance when evaluating ALS outcomes.}, } @article {pmid39215697, year = {2024}, author = {Burrows, DJ and McGown, A and Abduljabbar, O and Castelli, LM and Shaw, PJ and Hautbergue, GM and Ramesh, TM}, title = {RAN Translation of C9orf72-Related Dipeptide Repeat Proteins in Zebrafish Recapitulates Hallmarks of Amyotrophic Lateral Sclerosis and Identifies Hypothermia as a Therapeutic Strategy.}, journal = {Annals of neurology}, volume = {96}, number = {6}, pages = {1058-1069}, doi = {10.1002/ana.27068}, pmid = {39215697}, issn = {1531-8249}, support = {Apr17/854-791/MNDA_/Motor Neurone Disease Association/United Kingdom ; MR/R024162/1/MRC_/Medical Research Council/United Kingdom ; BB/S005277/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Animals ; *Zebrafish ; *C9orf72 Protein/genetics ; *Amyotrophic Lateral Sclerosis/genetics/therapy/metabolism ; *Animals, Genetically Modified ; *Disease Models, Animal ; *Dipeptides ; Hypothermia, Induced/methods ; Frontotemporal Dementia/genetics/metabolism ; Humans ; Protein Biosynthesis/genetics/physiology ; }, abstract = {OBJECTIVE: Hexanucleotide repeat expansions in the C9orf72 gene are the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). A large body of evidence implicates dipeptide repeats (DPRs) proteins as one of the main drivers of neuronal injury in cell and animal models.

METHODS: A pure repeat-associated non-AUG (RAN) translation zebrafish model of C9orf72-ALS/FTD was generated. Embryonic and adult transgenic zebrafish lysates were investigated for the presence of RAN-translated DPR species and adult-onset motor deficits. Using C9orf72 cell models as well as embryonic C9orf72-ALS/FTD zebrafish, hypothermic-therapeutic temperature management (TTM) was explored as a potential therapeutic option for C9orf72-ALS/FTD.

RESULTS: Here, we describe a pure RAN translation zebrafish model of C9orf72-ALS/FTD that exhibits significant RAN-translated DPR pathology and progressive motor decline. We further demonstrate that hypothermic-TTM results in a profound reduction in DPR species in C9orf72-ALS/FTD cell models as well as embryonic C9orf72-ALS/FTD zebrafish.

INTERPRETATION: The transgenic model detailed in this paper provides a medium throughput in vivo research tool to further investigate the role of RAN-translation in C9orf72-ALS/FTD and further understand the mechanisms that underpin neuroprotective strategies. Hypothermic-TTM presents a viable therapeutic avenue to explore in the context of C9orf72-ALS/FTD. ANN NEUROL 2024;96:1058-1069.}, } @article {pmid39215690, year = {2024}, author = {Suwa, S and Ando, M and Nakashima, T and Horii, S and Anai, T and Takeyama, H}, title = {In Situ Raman Hyperspectral Analysis of Microbial Colonies for Secondary Metabolites Screening.}, journal = {Analytical chemistry}, volume = {96}, number = {37}, pages = {14909-14917}, pmid = {39215690}, issn = {1520-6882}, mesh = {*Spectrum Analysis, Raman/methods ; *Escherichia coli/metabolism/isolation & purification ; Anti-Bacterial Agents/analysis/metabolism ; Streptomyces/metabolism ; Least-Squares Analysis ; }, abstract = {Since the discovery of penicillin, a vast array of microbial antibiotics has been identified and applied in the medical field. Globally, the search for drug candidates via microbial screening is ongoing. Traditional screening methods, however, are time-consuming and require labor-intensive sample processing, significantly reducing throughput. This research introduces a Raman spectroscopy-based screening system tailored to the in situ analysis of microbial colonies on solid culture media. Employing multivariate curve resolution-alternating least-squares (MCR-ALS) for spectral decomposition, our approach reveals the production of secondary metabolites at the single colony level. We enhanced the microbial culture method, enabling direct, high signal-to-noise (S/N) ratio Raman spectroscopic measurements of colonies of Escherichia coli and actinomycetes species. Through semisupervised MCR analysis using the known spectra of actinorhodin and undecylprodigiosin as references, we accurately assessed the production of these compounds by Streptomyces coelicolor A3(2). Furthermore, we herein successfully detected the production of amphotericin B by Streptomyces nodosus, even in the absence of prior spectral information. This demonstrates the potential of our technique in the discovery of secondary metabolites. In addition to enabling the detection of the above-mentioned compounds, this analysis revealed the heterogeneity of the spatial distribution of their production in each colony. Our technique makes a significant contribution to the advancement of microbial screening, offering a rapid, efficient alternative to conventional methods and opening avenues for secondary metabolites discovery.}, } @article {pmid39215326, year = {2024}, author = {Carlton, J and Powell, P and Rowen, D and Williams, C and Griffiths, AW and Hobson, E and McDermott, C}, title = {Development of a novel patient reported outcome measure for health-related quality of life in amyotrophic lateral sclerosis (PROQuALS): study protocol.}, journal = {Health and quality of life outcomes}, volume = {22}, number = {1}, pages = {69}, pmid = {39215326}, issn = {1477-7525}, mesh = {*Amyotrophic Lateral Sclerosis/psychology/therapy ; Humans ; *Quality of Life/psychology ; *Patient Reported Outcome Measures ; Surveys and Questionnaires ; Research Design ; Psychometrics ; Cost-Benefit Analysis ; }, abstract = {BACKGROUND: Patient reported outcome measures (PROMs) can be used to assess the impact of health conditions upon an individual's health-related quality of life (HRQoL). Whilst PROMs have been used to quantify the HRQoL impact of amyotrophic lateral sclerosis (ALS), existing instruments may not fully capture what matters to people living with ALS (plwALS) or be appropriate to be used directly to inform the cost-effectiveness of new treatments. This highlights a need for a new condition-specific PROM that can both capture what's important to plwALS and be used in economic evaluation. This study has two key aims: 1) to produce a novel PROM for measuring HRQoL in plwALS (PROQuALS). 2) to value a set of items from the novel PROM to generate an associated preference-weighted measure (PWM) that will enable utility values to be generated.

METHODS: A mixed-methods study design will be conducted across three stages. Stage 1 involves concept elicitation and the generation of draft PROM content from a robust and comprehensive systematic review of HRQoL in ALS, with input from plwALS. Stage 2 consists of cognitive debriefing of the draft PROM content to ascertain its content validity (Stage 2a), followed by a psychometric survey (Stage 2b) to assess statistical performance. Evidence from Stage 2 will be used to make decisions on the final content and format of the novel PROM. Stage 3 will involve valuation and econometric modeling using health economics methods to generate preference weights, so a PWM derived from the novel PROM can be used in the cost-effectiveness analyses of treatments. Patient and clinical advisory groups will have critical, collaborative input throughout the project.

DISCUSSION: The novel PROM will be designed to comprehensively assess important aspects of HRQoL to plwALS and to quantify HRQoL in terms of subjective impact. The PROQuALS measure will be available for use in research and healthcare settings. The associated PWM component will extend and enable the use of PROQuALS in cost-effective analyses of new treatments for ALS.

TRIAL REGISTRATION: Not applicable.}, } @article {pmid39211392, year = {2024}, author = {Matsuo, K and Nagamatsu, J and Nagata, K and Umeda, R and Shiota, T and Morimoto, S and Suzuki, N and Aoki, M and Okano, H and Nakamori, M and Nishihara, H}, title = {Establishment of a novel amyotrophic lateral sclerosis patient (TARDBP [N345K/+])-derived brain microvascular endothelial cell model reveals defective Wnt/β-catenin signaling: investigating diffusion barrier dysfunction and immune cell interaction.}, journal = {Frontiers in cell and developmental biology}, volume = {12}, number = {}, pages = {1357204}, pmid = {39211392}, issn = {2296-634X}, abstract = {Amyotrophic lateral sclerosis (ALS) is a major neurodegenerative disease for which there is currently no curative treatment. The blood-brain barrier (BBB), multiple physiological functions formed by mainly specialized brain microvascular endothelial cells (BMECs), serves as a gatekeeper to protect the central nervous system (CNS) from harmful molecules in the blood and aberrant immune cell infiltration. The accumulation of evidence indicating that alterations in the peripheral milieu can contribute to neurodegeneration within the CNS suggests that the BBB may be a previously overlooked factor in the pathogenesis of ALS. Animal models suggest BBB breakdown may precede neurodegeneration and link BBB alteration to the disease progression or even onset. However, the lack of a useful patient-derived model hampers understanding the pathomechanisms of BBB dysfunction and the development of BBB-targeted therapies. In this study, we differentiated BMEC-like cells from human induced pluripotent stem cells (hiPSCs) derived from ALS patients to investigate BMEC functions in ALS patients. TARDBP [N345K/+] carrying patient-derived BMEC-like cells exhibited increased permeability to small molecules due to loss of tight junction in the absence of neurodegeneration or neuroinflammation, highlighting that BMEC abnormalities in ALS are not merely secondary consequences of disease progression. Furthermore, they exhibited increased expression of cell surface adhesion molecules like ICAM-1 and VCAM-1, leading to enhanced immune cell adhesion. BMEC-like cells derived from hiPSCs with other types of TARDBP gene mutations (TARDBP [K263E/K263E] and TARDBP [G295S/G295S]) introduced by genome editing technology did not show such BMEC dysfunction compared to the isogenic control. Interestingly, transactive response DNA-binding protein 43 (TDP-43) was mislocalized to cytoplasm in TARDBP [N345K/+] carrying model. Wnt/β-catenin signaling was downregulated in the ALS patient (TARDBP [N345K/+])-derived BMEC-like cells and its activation rescued the leaky barrier phenotype and settled down VCAM-1 expressions. These results indicate that TARDBP [N345K/+] carrying model recapitulated BMEC abnormalities reported in brain samples of ALS patients. This novel patient-derived BMEC-like cell is useful for the further analysis of the involvement of vascular barrier dysfunctions in the pathogenesis of ALS and for promoting therapeutic drug discovery targeting BMEC.}, } @article {pmid39209824, year = {2024}, author = {Vieira de Sá, R and Sudria-Lopez, E and Cañizares Luna, M and Harschnitz, O and van den Heuvel, DMA and Kling, S and Vonk, D and Westeneng, HJ and Karst, H and Bloemenkamp, L and Varderidou-Minasian, S and Schlegel, DK and Mars, M and Broekhoven, MH and van Kronenburg, NCH and Adolfs, Y and Vangoor, VR and de Jongh, R and Ljubikj, T and Peeters, L and Seeler, S and Mocholi, E and Basak, O and Gordon, D and Giuliani, F and Verhoeff, T and Korsten, G and Calafat Pla, T and Venø, MT and Kjems, J and Talbot, K and van Es, MA and Veldink, JH and van den Berg, LH and Zelina, P and Pasterkamp, RJ}, title = {ATAXIN-2 intermediate-length polyglutamine expansions elicit ALS-associated metabolic and immune phenotypes.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {7484}, pmid = {39209824}, issn = {2041-1723}, mesh = {*Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology ; *Ataxin-2/genetics/metabolism ; Humans ; Animals ; *Peptides/metabolism/genetics ; Mice ; *Induced Pluripotent Stem Cells/metabolism ; *Motor Neurons/metabolism/pathology ; *Disease Models, Animal ; *Mice, Transgenic ; DNA-Binding Proteins/genetics/metabolism ; Phenotype ; Male ; Female ; Mitochondria/metabolism ; Neurites/metabolism ; }, abstract = {Intermediate-length repeat expansions in ATAXIN-2 (ATXN2) are the strongest genetic risk factor for amyotrophic lateral sclerosis (ALS). At the molecular level, ATXN2 intermediate expansions enhance TDP-43 toxicity and pathology. However, whether this triggers ALS pathogenesis at the cellular and functional level remains unknown. Here, we combine patient-derived and mouse models to dissect the effects of ATXN2 intermediate expansions in an ALS background. iPSC-derived motor neurons from ATXN2-ALS patients show altered stress granules, neurite damage and abnormal electrophysiological properties compared to healthy control and other familial ALS mutations. In TDP-43[Tg]-ALS mice, ATXN2-Q33 causes reduced motor function, NMJ alterations, neuron degeneration and altered in vitro stress granule dynamics. Furthermore, gene expression changes related to mitochondrial function and inflammatory response are detected and confirmed at the cellular level in mice and human neuron and organoid models. Together, these results define pathogenic defects underlying ATXN2-ALS and provide a framework for future research into ATXN2-dependent pathogenesis and therapy.}, } @article {pmid39210549, year = {2024}, author = {Yeo, CJJ and Simmons, Z}, title = {Caring for people living with ALS in Korea: challenges and possible paths forward.}, journal = {Muscle & nerve}, volume = {70}, number = {5}, pages = {881-883}, doi = {10.1002/mus.28241}, pmid = {39210549}, issn = {1097-4598}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy ; Republic of Korea/epidemiology ; Caregivers/psychology ; }, } @article {pmid39210467, year = {2024}, author = {Faggioli, G and Menotti, L and Marchesin, S and Chió, A and Dagliati, A and de Carvalho, M and Gromicho, M and Manera, U and Tavazzi, E and Di Nunzio, GM and Silvello, G and Ferro, N}, title = {An extensible and unifying approach to retrospective clinical data modeling: the BrainTeaser Ontology.}, journal = {Journal of biomedical semantics}, volume = {15}, number = {1}, pages = {16}, pmid = {39210467}, issn = {2041-1480}, support = {101017598//Horizon 2020 Framework Programme/ ; 101017598//Horizon 2020 Framework Programme/ ; 101017598//Horizon 2020 Framework Programme/ ; 101017598//Horizon 2020 Framework Programme/ ; 101017598//Horizon 2020 Framework Programme/ ; 101017598//Horizon 2020 Framework Programme/ ; 101017598//Horizon 2020 Framework Programme/ ; 101017598//Horizon 2020 Framework Programme/ ; 101017598//Horizon 2020 Framework Programme/ ; 101017598//Horizon 2020 Framework Programme/ ; 101017598//Horizon 2020 Framework Programme/ ; 101017598//Horizon 2020 Framework Programme/ ; }, mesh = {*Biological Ontologies ; Humans ; Retrospective Studies ; Amyotrophic Lateral Sclerosis ; Multiple Sclerosis ; Semantics ; }, abstract = {Automatic disease progression prediction models require large amounts of training data, which are seldom available, especially when it comes to rare diseases. A possible solution is to integrate data from different medical centres. Nevertheless, various centres often follow diverse data collection procedures and assign different semantics to collected data. Ontologies, used as schemas for interoperable knowledge bases, represent a state-of-the-art solution to homologate the semantics and foster data integration from various sources. This work presents the BrainTeaser Ontology (BTO), an ontology that models the clinical data associated with two brain-related rare diseases (ALS and MS) in a comprehensive and modular manner. BTO assists in organizing and standardizing the data collected during patient follow-up. It was created by harmonizing schemas currently used by multiple medical centers into a common ontology, following a bottom-up approach. As a result, BTO effectively addresses the practical data collection needs of various real-world situations and promotes data portability and interoperability. BTO captures various clinical occurrences, such as disease onset, symptoms, diagnostic and therapeutic procedures, and relapses, using an event-based approach. Developed in collaboration with medical partners and domain experts, BTO offers a holistic view of ALS and MS for supporting the representation of retrospective and prospective data. Furthermore, BTO adheres to Open Science and FAIR (Findable, Accessible, Interoperable, and Reusable) principles, making it a reliable framework for developing predictive tools to aid in medical decision-making and patient care. Although BTO is designed for ALS and MS, its modular structure makes it easily extendable to other brain-related diseases, showcasing its potential for broader applicability.Database URL https://zenodo.org/records/7886998 .}, } @article {pmid39209890, year = {2024}, author = {Prabhakaran, A and Thirumoorthi, P and Sri Dhivya Krishnan, K}, title = {Design and development of an intelligent zone based master electronic control unit for power optimization in electric vehicles.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {20142}, pmid = {39209890}, issn = {2045-2322}, abstract = {The development of electric vehicles (EVs) has been incremental because EVs satisfy a significant demand for energy sources. Electronic control unit (ECU) is an important component that processes the electric signals received from various sensors for generating the control signals for the actuators. Automotive control systems were initially operated manually throughout the automotive revolution based on the responses of input signals received from ECUs and drivers. Most of the functions in EV are controlled by the ECU and every ECU consumes power at all times even if it is not in use. The larger power consumption of passive ECUs like adaptive lighting systems (ALS), automatic wiper systems (AWS) brake light systems (BLS), etc., affect the life of ECUs and the range of EVs. This article is primarily concerned with limiting power consumption by switching the power supply to the passive ECUs based on their requirements. Hence, to achieve the objective, the intelligent zone (i-zone) based master ECU is triggered to activate the slave ECUs. Designing suites including Proteus and KiCAD were used for designing the circuits including master as well as slave ECU. This prototype is built using three secondary ECUs such as ALS & AWS and BLS which are controlled using i-zone-based master ECU. The performance of this implemented design is evaluated, and it is discovered that almost 40% of the battery consumption is reduced. This i-zone-based master ECU and all its slave ECUs manage power while ensuring the safety and reliability of EVs.}, } @article {pmid39208794, year = {2024}, author = {Choi, ES and Hnath, B and Sha, CM and Dokholyan, NV}, title = {Unveiling the double-edged sword: SOD1 trimers possess tissue-selective toxicity and bind septin-7 in motor neuron-like cells.}, journal = {Structure (London, England : 1993)}, volume = {32}, number = {10}, pages = {1776-1792.e5}, pmid = {39208794}, issn = {1878-4186}, support = {R35 GM134864/GM/NIGMS NIH HHS/United States ; UL1 TR002014/TR/NCATS NIH HHS/United States ; }, mesh = {Animals ; Male ; Mice ; Amyotrophic Lateral Sclerosis/metabolism/genetics ; Brain/metabolism ; Cell Cycle Proteins ; Models, Molecular ; *Motor Neurons/metabolism ; Muscle, Skeletal/metabolism ; *Protein Binding ; *Protein Multimerization ; *Septins/metabolism/genetics/chemistry ; Spinal Cord/metabolism ; *Superoxide Dismutase-1/metabolism/genetics/chemistry ; }, abstract = {Misfolded species of superoxide dismutase 1 (SOD1) are associated with increased death in amyotrophic lateral sclerosis (ALS) models compared to insoluble protein aggregates. The mechanism by which structurally independent SOD1 trimers cause cellular toxicity is unknown but may drive disease pathology. Here, we uncovered the SOD1 trimer interactome-a map of potential tissue-selective protein-binding partners in the brain, spinal cord, and skeletal muscle. We identified binding partners and key pathways associated with SOD1 trimers and found that trimers may affect normal cellular functions such as dendritic spine morphogenesis and synaptic function in the central nervous system and cellular metabolism in skeletal muscle. We discovered SOD1 trimer-selective enrichment of genes. We performed detailed computational and biochemical characterization of SOD1 trimer protein binding for septin-7. Our investigation highlights key proteins and pathways within distinct tissues, revealing a plausible intersection of genetic and pathophysiological mechanisms in ALS through interactions involving SOD1 trimers.}, } @article {pmid39207717, year = {2024}, author = {Ling, Y and Crotti, A}, title = {Emerging Microglial Therapies and Targets in Clinical Trial.}, journal = {Advances in neurobiology}, volume = {37}, number = {}, pages = {623-637}, pmid = {39207717}, issn = {2190-5215}, mesh = {*Microglia/metabolism ; Humans ; Clinical Trials as Topic ; Neurodegenerative Diseases/drug therapy/therapy/metabolism ; Nervous System Diseases/drug therapy/metabolism ; }, abstract = {Modulation of microglia function for treatment of neurodegenerative and neuropsychiatric disorders is an emerging field of neuroscience drug development. This is largely attributed to human genetic association studies combined with biological evidence indicating that the innate immune system acts as a causal contributor superimposed on the reactive component of neuronal loss in neurological dysfunction. The identification of disease risk gene variants that encode immune-modulatory proteins in microglia provides tools to evaluate how microglia cellular function or dysfunction affect neuronal health. The development of clinical stage therapeutic compounds that modify myeloid cell function enables us to investigate how modulating microglia function could become a transformational approach to mitigate neurological disorders. Improving our ability to boost microglia-promoting homeostatic and reparative functions hopefully will translate into achieving a better outcome for patients affected by neurological diseases. In this chapter, we aim to provide an overview of the microglial emerging therapies and targets being studied in current clinical trials.}, } @article {pmid39207711, year = {2024}, author = {Holtman, IR and Glass, CK and Nott, A}, title = {Interpretation of Neurodegenerative GWAS Risk Alleles in Microglia and their Interplay with Other Cell Types.}, journal = {Advances in neurobiology}, volume = {37}, number = {}, pages = {531-544}, pmid = {39207711}, issn = {2190-5215}, mesh = {Humans ; *Microglia/metabolism ; *Genome-Wide Association Study ; *Neurodegenerative Diseases/genetics ; *Genetic Predisposition to Disease ; Alleles ; Alzheimer Disease/genetics ; }, abstract = {Microglia have been implicated in numerous neurodegenerative and neuroinflammatory disorders; however, the causal contribution of this immune cell type is frequently debated. Genetic studies offer a unique vantage point in that they infer causality over a secondary consequence. Genome-wide association studies (GWASs) have identified hundreds of loci in the genome that are associated with susceptibility to neurodegenerative disorders. GWAS studies implicate microglia in the pathogenesis of Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), and to a lesser degree suggest a role for microglia in vascular dementia (VaD), frontotemporal dementia (FTD), and amyotrophic lateral sclerosis (ALS), and other neurodegenerative and neuropsychiatric disorders. The contribution and function of GWAS risk loci on disease progression is an ongoing field of study, in which large genomic datasets, and an extensive framework of computational tools, have proven to be crucial. Several GWAS risk loci are shared between disorders, pointing towards common pleiotropic mechanisms. In this chapter, we introduce key concepts in GWAS and post-GWAS interpretation of neurodegenerative disorders, with a focus on GWAS risk genes implicated in microglia, their interplay with other cell types and shared convergence of GWAS risk loci on microglia.}, } @article {pmid39207709, year = {2024}, author = {Awogbindin, I and Wanklin, M and Verkhratsky, A and Tremblay, MÈ}, title = {Microglia in Neurodegenerative Diseases.}, journal = {Advances in neurobiology}, volume = {37}, number = {}, pages = {497-512}, pmid = {39207709}, issn = {2190-5215}, mesh = {*Microglia/metabolism/pathology ; Humans ; *Neurodegenerative Diseases/metabolism ; Alzheimer Disease/metabolism/pathology ; Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology/physiopathology ; Animals ; Parkinson Disease/metabolism ; }, abstract = {Neurodegenerative diseases are manifested by a progressive death of neural cells, resulting in the deterioration of central nervous system (CNS) functions, ultimately leading to specific behavioural and cognitive symptoms associated with affected brain regions. Several neurodegenerative disorders are caused by genetic variants or mutations, although the majority of cases are sporadic and linked to various environmental risk factors, with yet an unknown aetiology. Neuroglial changes are fundamental and often lead to the pathophysiology of neurodegenerative diseases. In particular, microglial cells, which are essential for maintaining CNS health, become compromised in their physiological functions with the exposure to environmental risk factors, genetic variants or mutations, as well as disease pathology. In this chapter, we cover the contribution of neuroglia, especially microglia, to several neurodegenerative diseases, including Nasu-Hakola disease, Parkinson's disease, amyotrophic lateral sclerosis, Alzheimer's disease, Huntington's disease, infectious disease-associated neurodegeneration, and metal-precipitated neurodegeneration. Future research perspectives for the field pertaining to the therapeutic targeting of microglia across these disease conditions are also discussed.}, } @article {pmid39207520, year = {2024}, author = {Bjelica, B and Petri, S}, title = {Narrative review of diagnosis, management and treatment of dysphagia and sialorrhea in amyotrophic lateral sclerosis.}, journal = {Journal of neurology}, volume = {271}, number = {10}, pages = {6508-6513}, pmid = {39207520}, issn = {1432-1459}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/complications/therapy/diagnosis ; *Sialorrhea/etiology/therapy/diagnosis ; *Deglutition Disorders/etiology/therapy/diagnosis/physiopathology ; Disease Management ; }, abstract = {The degenerative motor neuron disorder amyotrophic lateral sclerosis (ALS) frequently leads bulbar symptoms like dysarthria, dysphagia, and sialorrhea, in approximately one-third of cases being the initial symptom. Throughout the disease, more than two-thirds of ALS patients experience dysphagia, regardless of the region of onset. In this review, we aimed to offer an updated overview of dysphagia and sialorrhea in ALS, covering its diagnosis, monitoring, and treatment in clinical practice. Regular assessment of dysphagia and sialorrhea during each patient visit is essential and should be a standard aspect of ALS care. Early discussion of potential treatments such as high-calorie diets or percutaneous endoscopic gastrostomy (PEG) is crucial. Furthermore, this review highlights and discusses potential areas for improvement in both clinical practice and research.}, } @article {pmid39207268, year = {2024}, author = {Han, H and Guo, G and Zhang, S and Peng, R and Xia, C}, title = {Reduced Surface Area for the Oxygen Reduction Reaction in Porous Electrode via Electrical Conductivity Relaxation.}, journal = {Chemistry (Weinheim an der Bergstrasse, Germany)}, volume = {30}, number = {68}, pages = {e202402785}, doi = {10.1002/chem.202402785}, pmid = {39207268}, issn = {1521-3765}, support = {(2021YFB4001401//the National Key R&D Program of China/ ; 52272247//the National Natural Science Foundation of China/ ; }, abstract = {Oxygen reduction reaction (ORR) performance of porous electrodes is critical for solid oxide fuel cells (SOFCs). However, the effects of gas diffusion on the ORR in porous media need further investigation, although some issues, such as nonthermal surface oxygen exchange, have been attributed to gas diffusion. Herein, La0.6Sr0.4Co0.2Fe0.8O3-δ (LSCF) with various porosity, pore radii, and gas permeability were investigated via the electrical conductivity relaxation method and analysed via the distributed of characteristic time (DCT) model. The ORR is revealed with three characteristic times, which are gas diffusion, oxygen exchange via the surface corresponding to small pores, and oxygen exchange to large pores. Gas diffusion delays the oxygen surface exchange reaction, resulting in a very low chemical oxygen surface exchange coefficient compared with that obtained with dense samples under the assumption that all the surfaces are active for the ORR. Reduced surface area is thus defined to quantitatively represent the gas diffusion effects. The reduced surface area increases with increasing gas permeability, demonstrating the importance of electrode engineering for fast gas transport. Moreover, reduced surface area is suggested for replacing the specific surface area to calculate the electrode polarization impedance via the ALS model.}, } @article {pmid39206899, year = {2024}, author = {Ma, J and Liu, J and Chen, S and Zhang, W and Wang, T and Cao, M and Yang, Y and Du, Y and Cui, G and Du, Z}, title = {Understanding the Mechanism of Ferroptosis in Neurodegenerative Diseases.}, journal = {Frontiers in bioscience (Landmark edition)}, volume = {29}, number = {8}, pages = {291}, doi = {10.31083/j.fbl2908291}, pmid = {39206899}, issn = {2768-6698}, support = {81602893//National Natural Science Foundation of China (NSFC)/ ; ZR2015YL049//Natural Science Foundation of Shandong Province/ ; ZR2021MH218//Natural Science Foundation of Shandong Province/ ; ZR2022MH184//Natural Science Foundation of Shandong Province/ ; 202104020224//Shandong Province Medical and Health Technology Development Plan/ ; 202312010854//Shandong Province Medical and Health Technology Development Plan/ ; Z-2023114//Shandong Province Traditional Chinese Medicine Science and Technology Plan/ ; 202328074//Jinan Science and Technology Plan/ ; }, mesh = {*Ferroptosis/physiology ; Humans ; *Neurodegenerative Diseases/metabolism/physiopathology ; *Iron/metabolism ; Animals ; Neurons/metabolism/pathology ; }, abstract = {Neurodegenerative disorders are typified by the progressive degeneration and subsequent apoptosis of neuronal cells. They encompass a spectrum of conditions, including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), epilepsy, brian ischemia, brian injury, and neurodegeneration with brain iron accumulation (NBIA). Despite the considerable heterogeneity in their clinical presentation, pathophysiological underpinning and disease trajectory, a universal feature of these disorders is the functional deterioration of the nervous system concomitant with neuronal apoptosis. Ferroptosis is an iron (Fe)-dependent form of programmed cell death that has been implicated in the pathogenesis of these conditions. It is intricately associated with intracellular Fe metabolism and lipid homeostasis. The accumulation of Fe is observed in a variety of neurodegenerative diseases and has been linked to their etiology and progression, although its precise role in these pathologies has yet to be elucidated. This review aims to elucidate the characteristics and regulatory mechanisms of ferroptosis, its association with neurodegenerative diseases, and recent advances in ferroptosis-targeted therapeutic strategies. Ferroptosis may therefore be a critical area for future research into neurodegenerative diseases.}, } @article {pmid39206288, year = {2024}, author = {Cui, Y and Li, C and Ke, B and Xiao, Y and Wang, S and Jiang, Q and Zheng, X and Lin, J and Huang, J and Shang, H}, title = {Protective role of serum albumin in dementia: a prospective study from United Kingdom biobank.}, journal = {Frontiers in neurology}, volume = {15}, number = {}, pages = {1458184}, pmid = {39206288}, issn = {1664-2295}, abstract = {BACKGROUND: A number of studies have explored the link between neurodegenerative disorders (NDDs) and albumin, the main protein in human plasma. However, the results have been inconsistent, highlighting the necessity for a detailed systemic analysis.

METHODS: Utilizing data from the United Kingdom Biobank, we investigated the relationship between baseline levels of serum and urine albumin and the occurrence of common NDDs, including Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and dementia, employing Cox proportional hazards regression analysis.

RESULTS: Our results reveal that elevated baseline serum albumin levels are linked to a decreased risk of developing dementia (beta = -0.024, SE = 0.004, p < 0.001). Subgroup and interaction analyses highlighted the impact of factors like body mass index (BMI), age, and alcohol consumption on this relationship. Specifically, participants with higher BMI, younger age, or lower alcohol intake exhibited a stronger protective effect. On the other hand, a higher baseline level of urine microalbumin was connected to a slight increase in dementia risk (beta = 0.003, SE = 3.30E-04, p < 0.001). No significant associations were found between albumin levels and the risk of PD or ALS.

CONCLUSION: Our study underscores the potential role of serum albumin as a biomarker associated with reduced dementia risk. These findings contribute valuable insights into the understanding of albumin's impact on NDDs, suggesting its utility as a biomarker for dementia in clinical settings and informing future therapeutic strategies in clinical trials.}, } @article {pmid39206217, year = {2024}, author = {Uzelac, Z and Schwäble, B and Dorst, J and Rosenbohm, A and Wollinsky, K and Wurster, CD and Steinbreier, JS and Ludolph, AC}, title = {Pattern of pareses in 5q-spinal muscular atrophy.}, journal = {Therapeutic advances in neurological disorders}, volume = {17}, number = {}, pages = {17562864241263420}, pmid = {39206217}, issn = {1756-2856}, abstract = {BACKGROUND: This prospective study investigates the pattern of pareses in 5q-associated spinal muscular atrophy (SMA) to identify disease-specific characteristics and potential differences from amyotrophic lateral sclerosis (ALS) and spinobulbar muscular atrophy (SBMA). Detailed knowledge about pareses patterns in SMA facilitates differential diagnosis and supports therapeutic monitoring.

METHODS: Between January 2021, and June 2021, 66 SMA patients (59.1% male, aged 33.6 ± 15.2 years) were included in the study. Most patients had SMA type II (n = 28) or SMA type III (n = 28), seven patients had SMA type I, and three patients had SMA type IV. We analyzed the pattern of pareses using the UK Medical Research Council (MRC) scoring system.

RESULTS: In both, upper and lower limbs muscle weakness was less pronounced in distal (upper limbs: MRC median 3.0 (interquartile range 1.5-3.5); lower limbs: 1.5 (0.5-3.0)) compared to proximal muscle groups (upper limbs: 2.0 (1.5-2.6); p < 0.001; lower limbs: 0.5 (0.5-1.5); p < 0.001). Thenar muscles were stronger than other small hand muscles (3.0 (2.0-3.5) vs 3.0 (1.5-3.5); p = 0.004). Muscles had more strength in upper (2.3 (1.5-3.1)) compared to lower limbs (1.1 (0.5-2.3); p < 0.001) and in flexors compared to extensors.

CONCLUSION: We identified a specific pattern of muscle paresis in SMA which is different from the pattern of paresis in ALS and SBMA. As a rule of thumb, the pattern of pareses is similar, but not identical to ALS in distal, but different in proximal muscle groups.}, } @article {pmid39205388, year = {2024}, author = {Jafarinia, H and Van der Giessen, E and Onck, PR}, title = {C9orf72 polyPR interaction with the nuclear pore complex.}, journal = {Biophysical journal}, volume = {123}, number = {20}, pages = {3533-3539}, pmid = {39205388}, issn = {1542-0086}, mesh = {*Nuclear Pore/metabolism/chemistry ; *C9orf72 Protein/genetics/metabolism/chemistry ; *Molecular Dynamics Simulation ; Nuclear Pore Complex Proteins/metabolism/chemistry/genetics ; Protein Binding ; Saccharomyces cerevisiae/metabolism/genetics ; Active Transport, Cell Nucleus ; Humans ; }, abstract = {The C9orf72 gene associated with amyotrophic lateral sclerosis/frontotemporal dementia is translated to five dipeptide repeat proteins, among which poly-proline-arginine (PR) is the most toxic in cell and animal models, contributing to a variety of cellular defects. It has been proposed that polyPR disrupts nucleocytoplasmic transport (NCT) through several mechanisms including accumulation in the nuclear pore complex (NPC), accumulation in the nucleolus, and direct interactions with transport receptors. The NPC, which is the key regulator of transport between the cytoplasm and nucleus, plays a central role in these suggested mechanisms. Exploring polyPR interaction with the NPC provides valuable insight into the molecular details of polyPR-mediated NCT defects. To address this, we use coarse-grained molecular dynamics models of polyPR and the yeast NPC lined with intrinsically disordered FG-nucleoporins (FG-Nups). Our findings indicate no aggregation of polyPR within the NPC or permanent binding to FG-Nups. Instead, polyPR translocates through the NPC, following a trajectory through the central low-density region of the pore. In the case of longer polyPRs, we observe a higher energy barrier for translocation and a narrower translocation channel. Our study shows that polyPR and FG-Nups are mainly engaged in steric interactions inside the NPC with only a small contribution of specific cation-pi, hydrophobic, and electrostatic interactions, allowing polyPR to overcome the entropic barrier of the NPC in a size-dependent manner.}, } @article {pmid39204741, year = {2024}, author = {Xu, X and Zhao, B and Shen, B and Qi, Z and Wang, J and Cui, H and Li, B and Chen, S and Wang, G and Liu, X}, title = {Using RNA-Seq Analysis to Select Key Genes Related to Seed Dormancy in ALS-Inhibiting Resistant Descurainia sophia with Pro-197-Thr Mutation.}, journal = {Plants (Basel, Switzerland)}, volume = {13}, number = {16}, pages = {}, pmid = {39204741}, issn = {2223-7747}, support = {2024060203//Basic Research Funds of Hebei Academy of Agriculture and Forestry Sciences/ ; 2023LYS03//HAAFS Youth Innovation Fund Project/ ; 2022KJCXZX-LYS-13//HAAFS Science and Technology Innovation Special Project/ ; }, abstract = {Flixweed (Descurainia sophia) is a weed that seriously affects wheat fields in China. Over the past 20 years, it has evolved resistance to the herbicide tribenuron-methyl. In the present study, a resistant D. sophia population with a Pro-197-Thr mutation of acetolactate synthetase (ALS) was found to have a resistance index of 457.37 for tribenuron-methyl. Under the same growth conditions, the seeds of resistant (R) and susceptible (S) populations exhibited similar vitality but the germination rates of R seeds were higher than those of S seeds. This result demonstrated that seed dormancy periods were shorter in the R seeds. RNA-Seq transcriptome analysis was then used to choose candidate genes that could regulate seed dormancy pathways in the R population. A total of 504,976,046 clean reads were selected from nine RNA-Seq libraries and assembled into 79,729 unigenes. Among these, 33,476 unigenes were assigned to 51 GO subgroups, and 26,117 unigenes were assigned to 20 KEGG secondary metabolic pathways. Next, 2473 differentially expressed genes (DEGs) were divided into three groups, as follows: G-24 h (germinating seeds) vs. D (dormant seeds); G-48 h (germinated seeds) vs. D; and G-48 h vs. G-24 h. From these 2473 DEGs, 8 were selected as candidate dormancy unigenes for the R population if their expression levels continuously decreased during the seed germination progress and their functional annotations were related to plant seed dormancy. One candidate unigene was annotated as CYP707A2; two unigenes were annotated as the transcription factors TGA4 and TGA2; one unigene was annotated as the cystathionine beta-synthase gene; and four unigenes could not be annotated as any gene listed in the six public databases. However, qRT-PCR-validated results showed that, during the germination of R seeds, the expression of the three candidate unigenes first decreased and then increased, indicating that they may have other growth-regulating functions in R populations. In brief, the dormancy function of the eight candidate dormancy unigenes needs to be further studied.}, } @article {pmid39204338, year = {2024}, author = {O'Neill, R and Yoo, O and Burcham, P and Lim, LY}, title = {Edaravone for the Treatment of Motor Neurone Disease: A Critical Review of Approved and Alternative Formulations against a Proposed Quality Target Product Profile.}, journal = {Pharmaceutics}, volume = {16}, number = {8}, pages = {}, pmid = {39204338}, issn = {1999-4923}, support = {000990//Australian Government Research Training Program, Stan Perron Charitable Foundation/ ; }, abstract = {Edaravone is one of two main drugs for treating motor neurone disease (MND). This review proposes a specific quality target product profile (QTPP) for edaravone following an appraisal of the issues accounting for the poor clinical uptake of the approved IV and oral liquid edaravone formulations. This is followed by a review of the alternative oral formulations of edaravone described in the published patent and journal literature against the QTPP. A total of 14 texts published by six research groups on 18 novel oral formulations of edaravone for the treatment of MND have been reviewed. The alternative oral formulations included liquid and solid formulations developed with cyclodextrins, lipids, surfactants, co-surfactants, alkalising agents, tablet excipients, and co-solvents. Most were intended to deliver edaravone for drug absorption in the lower gastrointestinal tract (GIT); however, there were also four formulations targeting the oral mucosal absorption of edaravone to avoid first-pass metabolism. All the novel formulations improved the aqueous solubility, stability, and oral bioavailability (BA) of edaravone compared to an aqueous suspension of edaravone. A common limitation of the published formulations is the lack of MND-patient-centred data. Except for TW001, no other formulations have been trialled in MND patients. To meet the QTPP of an oral edaravone formulation for MND patients, it is recommended that a tablet of appropriate size and with acceptable taste and stability be designed for the effective sublingual or buccal absorption of edaravone. This tablet should be designed with input from the MND community.}, } @article {pmid39203762, year = {2024}, author = {Zarco-Martín, MT and Freire, C and Andreo-López, MC and Leyva-Martínez, S and Fernández-Soto, ML}, title = {Malnutrition in Amyotrophic Lateral Sclerosis: Insights from Morphofunctional Assessment and Global Leadership Initiative on Malnutrition Criteria.}, journal = {Nutrients}, volume = {16}, number = {16}, pages = {}, pmid = {39203762}, issn = {2072-6643}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/complications/physiopathology ; Female ; Male ; *Malnutrition/epidemiology/diagnosis ; Middle Aged ; Aged ; Cross-Sectional Studies ; *Nutrition Assessment ; Hand Strength ; Prevalence ; Nutritional Status ; Electric Impedance ; Severity of Illness Index ; }, abstract = {Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disease frequently accompanied by malnutrition due to weight loss, increased energy expenditure, and muscle mass loss. This study aimed to evaluate morphofunctional assessment tools as predictors of malnutrition and to investigate their relationship with muscle status and disease severity in ALS patients. A cross-sectional study was conducted with 45 ALS patients at the San Cecilio University Hospital in Granada. Malnutrition was assessed using the Global Leadership Initiative on Malnutrition (GLIM) criteria. Morphofunctional assessment was performed using Bioimpedance Vectorial Analysis (BIVA), handgrip strength (HGS), and Short Physical Performance Battery (SPPB). Malnutrition prevalence was 38% according to GLIM criteria. Significant differences were observed between malnourished and non-malnourished groups in age (70 ± 9 vs. 62 ± 10 years, p = 0.01), sex (female prevalence: 58.8% vs. 25.0%, p = 0.02), dysphagia prevalence (83% vs. 29%, p < 0.001), PEG/PRG use (35.3% vs. 3.6%, p = 0.01), and ALSFRS-R scores (30 ± 12 vs. 34 ± 12, p = 0.02). Malnourished patients had lower values in anthropometric measurements, muscle mass obtained by BIVA, and phase angle (PA) (4.05 ± 0.8° vs. 5.09 ± 0.8°, p < 0.001). No significant differences were found in muscle strength or functional status. PA showed significant correlations with muscle strength (r = 0.52, p < 0.001) and muscle mass measures (r = 0.48, p < 0.001). Moreover, PA was associated with poorer disease progression and physical performance. In our sample, BIVA metrics such as PA (<4.3°), SPA (<-0.8), body cell mass (<9.2 kg/m), and extracellular water (>49.75%) were identified as malnutrition risk factors. The study underscores the critical importance of comprehensive morphofunctional assessment and the use of advanced diagnostic criteria, for early identification and intervention in malnutrition among people with ALS. Further research is warranted to validate these findings and develop targeted nutritional strategies into routine clinical practice.}, } @article {pmid39202683, year = {2024}, author = {Gianferrari, G and Zucchi, E and Martinelli, I and Simonini, C and Fini, N and Ferro, S and Mercati, A and Ferri, L and Filippini, T and Vinceti, M and Mandrioli, J}, title = {Trends in Hospital Admissions for Patients with Amyotrophic Lateral Sclerosis: Insights from a Retrospective Cohort Study in a Province in Northern Italy.}, journal = {Life (Basel, Switzerland)}, volume = {14}, number = {8}, pages = {}, pmid = {39202683}, issn = {2075-1729}, support = {//Servizio sanitario dell'Emilia-Romagna/ ; not available//Emilia Romagna Regional Health Authority/ ; }, abstract = {ALS is characterized by a highly heterogeneous course, ranging from slow and uncomplicated to rapid progression with severe extra-motor manifestations. This study investigated ALS-related hospitalizations and their connection to clinical aspects, comorbidities, and prognosis. We performed a retrospective cohort study including patients residing in Modena, Italy, newly diagnosed between 2007 and 2017 and followed up until 31 December 2022. Data were obtained from the Emilia Romagna ALS registry, regional hospitals, and medical records. Among the 249 patients, there were 492 hospital admissions, excluding those for diagnostic purposes; 63% of the patients had at least one hospitalization post-diagnosis, with an average stay of 19.90 ± 23.68 days. Younger patients were more likely to be hospitalized multiple times and experienced longer stays (44.23 ± 51.71 days if <65 years; 26.46 ± 36.02 days if older, p < 0.001). Patients who were hospitalized at least once more frequently underwent gastrostomy (64.97%) or non-invasive (66.24%) and invasive (46.50%) ventilation compared to those never hospitalized (21.74%, 31.52%, 13.04%, respectively, p < 0.001 for all). Emergency procedures led to longer hospitalizations (62.84 ± 48.91 days for non-invasive ventilation in emergencies vs. 39.88 ± 46.46 days electively, p = 0.012). Tracheostomy-free survival was not affected by hospitalizations. In conclusion, younger ALS patients undergo frequent and prolonged hospitalizations, especially after emergency interventions, although these do not correlate with reduced survival.}, } @article {pmid39201793, year = {2024}, author = {Martin, LJ and Koh, SJ and Price, A and Park, D and Kim, BW}, title = {Nuclear Localization of Human SOD1 in Motor Neurons in Mouse Model and Patient Amyotrophic Lateral Sclerosis: Possible Links to Cholinergic Phenotype, NADPH Oxidase, Oxidative Stress, and DNA Damage.}, journal = {International journal of molecular sciences}, volume = {25}, number = {16}, pages = {}, pmid = {39201793}, issn = {1422-0067}, support = {R01 NS052098/NS/NINDS NIH HHS/United States ; R01 AG016282/AG/NIA NIH HHS/United States ; R01 NS034100/NS/NINDS NIH HHS/United States ; NS34100/NS/NINDS NIH HHS/United States ; R01 NS079348/NS/NINDS NIH HHS/United States ; R01 NS065895/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Humans ; Mice ; *Amyotrophic Lateral Sclerosis/metabolism/genetics/pathology ; *Cell Nucleus/metabolism ; Disease Models, Animal ; *DNA Damage ; *Induced Pluripotent Stem Cells/metabolism ; Mice, Transgenic ; *Motor Neurons/metabolism/pathology ; NADPH Oxidases/metabolism/genetics ; *Oxidative Stress ; Phenotype ; Spinal Cord/metabolism/pathology ; *Superoxide Dismutase-1/genetics/metabolism ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal disease that causes degeneration of motor neurons (MNs) and paralysis. ALS can be caused by mutations in the gene that encodes copper/zinc superoxide dismutase (SOD1). SOD1 is known mostly as a cytosolic antioxidant protein, but SOD1 is also in the nucleus of non-transgenic (tg) and human SOD1 (hSOD1) tg mouse MNs. SOD1's nuclear presence in different cell types and subnuclear compartmentations are unknown, as are the nuclear functions of SOD1. We examined hSOD1 nuclear localization and DNA damage in tg mice expressing mutated and wildtype variants of hSOD1 (hSOD1-G93A and hSOD1-wildtype). We also studied ALS patient-derived induced pluripotent stem (iPS) cells to determine the nuclear presence of SOD1 in undifferentiated and differentiated MNs. In hSOD1-G93A and hSOD1-wildtype tg mice, choline acetyltransferase (ChAT)-positive MNs had nuclear hSOD1, but while hSOD1-wildtype mouse MNs also had nuclear ChAT, hSOD1-G93A mouse MNs showed symptom-related loss of nuclear ChAT. The interneurons had preserved parvalbumin nuclear positivity in hSOD1-G93A mice. hSOD1-G93A was seen less commonly in spinal cord astrocytes and, notably, oligodendrocytes, but as the disease emerged, the oligodendrocytes had increased mutant hSOD1 nuclear presence. Brain and spinal cord subcellular fractionation identified mutant hSOD1 in soluble nuclear extracts of the brain and spinal cord, but mutant hSOD1 was concentrated in the chromatin nuclear extract only in the spinal cord. Nuclear extracts from mutant hSOD1 tg mouse spinal cords had altered protein nitration, footprinting peroxynitrite presence, and the intact nuclear extracts had strongly increased superoxide production as well as the active NADPH oxidase marker, p47phox. The comet assay showed that MNs from hSOD1-G93A mice progressively (6-14 weeks of age) accumulated DNA single-strand breaks. Ablation of the NCF1 gene, encoding p47phox, and pharmacological inhibition of NADPH oxidase with systemic treatment of apocynin (10 mg/kg, ip) extended the mean lifespan of hSOD1-G93A mice by about 25% and mitigated genomic DNA damage progression. In human postmortem CNS, SOD1 was found in the nucleus of neurons and glia; nuclear SOD1 was increased in degenerating neurons in ALS cases and formed inclusions. Human iPS cells had nuclear SOD1 during directed differentiation to MNs, but mutant SOD1-expressing cells failed to establish wildtype MN nuclear SOD1 levels. We conclude that SOD1 has a prominent nuclear presence in the central nervous system, perhaps adopting aberrant contexts to participate in ALS pathobiology.}, } @article {pmid39201731, year = {2024}, author = {Fang, C and Wu, J and Liang, W}, title = {Systematic Investigation of Aluminum Stress-Related Genes and Their Critical Roles in Plants.}, journal = {International journal of molecular sciences}, volume = {25}, number = {16}, pages = {}, pmid = {39201731}, issn = {1422-0067}, support = {242102111164; 222301420106//Key R&D and Promotion Projects in Henan Province; Henan Science & Technology Research and Development Plan Joint Fund/ ; }, mesh = {*Aluminum/toxicity ; *Stress, Physiological/genetics ; *Gene Expression Regulation, Plant/drug effects ; Plant Proteins/genetics/metabolism ; Zea mays/genetics/growth & development/metabolism/drug effects ; Plants/genetics/metabolism/drug effects ; Genes, Plant ; }, abstract = {Aluminum (Al) stress is a dominant obstacle for plant growth in acidic soil, which accounts for approximately 40-50% of the world's potential arable land. The identification and characterization of Al stress response (Al-SR) genes in Arabidopsis, rice, and other plants have deepened our understanding of Al's molecular mechanisms. However, as a crop sensitive to acidic soil, only eight Al-SR genes have been identified and functionally characterized in maize. In this review, we summarize the Al-SR genes in plants, including their classifications, subcellular localizations, expression organs, functions, and primarily molecular regulatory networks. Moreover, we predict 166 putative Al-SR genes in maize based on orthologue analyses, facilitating a comprehensive understanding of the impact of Al stress on maize growth and development. Finally, we highlight the potential applications of alleviating Al toxicity in crop production. This review deepens our understanding of the Al response in plants and provides a blueprint for alleviating Al toxicity in crop production.}, } @article {pmid39201466, year = {2024}, author = {Strong, MJ and McLellan, C and Kaplanis, B and Droppelmann, CA and Junop, M}, title = {Phase Separation of SARS-CoV-2 Nucleocapsid Protein with TDP-43 Is Dependent on C-Terminus Domains.}, journal = {International journal of molecular sciences}, volume = {25}, number = {16}, pages = {}, pmid = {39201466}, issn = {1422-0067}, support = {201806SOP-411481/CAPMC/CIHR/Canada ; not applicable//Temerty Family Foundation/ ; }, mesh = {*DNA-Binding Proteins/metabolism/chemistry ; Humans ; *SARS-CoV-2/metabolism/chemistry ; *Coronavirus Nucleocapsid Proteins/metabolism/chemistry/genetics ; *Protein Domains ; COVID-19/virology/metabolism ; Protein Binding ; Biomolecular Condensates/metabolism/chemistry ; RNA, Viral/metabolism/genetics ; Phosphoproteins/metabolism/chemistry ; Phase Separation ; }, abstract = {The SARS-CoV-2 nucleocapsid protein (N protein) is critical in viral replication by undergoing liquid-liquid phase separation to seed the formation of a ribonucleoprotein (RNP) complex to drive viral genomic RNA (gRNA) translation and in suppressing both stress granules and processing bodies, which is postulated to increase uncoated gRNA availability. The N protein can also form biomolecular condensates with a broad range of host endogenous proteins including RNA binding proteins (RBPs). Amongst these RBPs are proteins that are associated with pathological, neuronal, and glial cytoplasmic inclusions across several adult-onset neurodegenerative disorders, including TAR DNA binding protein 43 kDa (TDP-43) which forms pathological inclusions in over 95% of amyotrophic lateral sclerosis cases. In this study, we demonstrate that the N protein can form biomolecular condensates with TDP-43 and that this is dependent on the N protein C-terminus domain (N-CTD) and the intrinsically disordered C-terminus domain of TDP-43. This process is markedly accelerated in the presence of RNA. In silico modeling suggests that the biomolecular condensate that forms in the presence of RNA is composed of an N protein quadriplex in which the intrinsically disordered TDP-43 C terminus domain is incorporated.}, } @article {pmid39201350, year = {2024}, author = {Bedja-Iacona, L and Richard, E and Marouillat, S and Brulard, C and Alouane, T and Beltran, S and Andres, CR and Blasco, H and Corcia, P and Veyrat-Durebex, C and Vourc'h, P}, title = {Post-Translational Variants of Major Proteins in Amyotrophic Lateral Sclerosis Provide New Insights into the Pathophysiology of the Disease.}, journal = {International journal of molecular sciences}, volume = {25}, number = {16}, pages = {}, pmid = {39201350}, issn = {1422-0067}, mesh = {*Amyotrophic Lateral Sclerosis/genetics/metabolism ; Humans ; *Protein Processing, Post-Translational ; *Superoxide Dismutase-1/genetics/metabolism ; *RNA-Binding Protein FUS/metabolism/genetics ; DNA-Binding Proteins/metabolism/genetics ; Protein Serine-Threonine Kinases/metabolism/genetics ; Mutation ; Animals ; Phosphorylation ; Acetylation ; }, abstract = {Post-translational modifications (PTMs) affecting proteins during or after their synthesis play a crucial role in their localization and function. The modification of these PTMs under pathophysiological conditions, i.e., their appearance, disappearance, or variation in quantity caused by a pathological environment or a mutation, corresponds to post-translational variants (PTVs). These PTVs can be directly or indirectly involved in the pathophysiology of diseases. Here, we present the PTMs and PTVs of four major amyotrophic lateral sclerosis (ALS) proteins, SOD1, TDP-43, FUS, and TBK1. These modifications involve acetylation, phosphorylation, methylation, ubiquitination, SUMOylation, and enzymatic cleavage. We list the PTM positions known to be mutated in ALS patients and discuss the roles of PTVs in the pathophysiological processes of ALS. In-depth knowledge of the PTMs and PTVs of ALS proteins is needed to better understand their role in the disease. We believe it is also crucial for developing new therapies that may be more effective in ALS.}, } @article {pmid39200952, year = {2024}, author = {Schwarzenbacher, L and Wassermann, L and Rezar-Dreindl, S and Reiter, GS and Schmidt-Erfurth, U and Stifter, E}, title = {An Analysis of Ocular Biometrics: A Comprehensive Retrospective Study in a Large Cohort of Pediatric Cataract Patients.}, journal = {Journal of clinical medicine}, volume = {13}, number = {16}, pages = {}, pmid = {39200952}, issn = {2077-0383}, abstract = {Objectives: This study aims to provide a comprehensive analysis of ocular biometric parameters in pediatric patients with cataracts to optimize surgical outcomes. By evaluating various biometric data, we seek to enhance the decision-making process for intraocular lens (IOL) placement, particularly with advanced technologies like femtosecond lasers. Methods: This retrospective comparative study included pediatric patients with cataracts who underwent ocular biometric measurements and cataract extraction with anterior vitrectomy at the Medical University of Vienna between January 2019 and December 2021. Parameters measured included corneal diameter (CD), axial length (AL), corneal thickness (CT) and flat and steep keratometry (Kf and Ks). The study explored the correlations between these parameters and IOL placement. Results: A total of 136 eyes from 68 pediatric patients were included in the study. Significant positive correlations were found between corneal diameter, age and AL. The mean CD was 11.4 mm, mean AL was 19.5 mm, CT was 581.2 ± 51.8 µm, Kf was 7.76 ± 0.55 mm and Ks 7.41 ± 0.59 mm, respectively. Older pediatric patients with larger corneal diameters and longer ALs were more likely to receive in-the-bag IOL implantation. Conversely, younger patients often required alternative IOL placements or remained aphakic. Our data indicated that over 95% of the study population and all patients aged one year and older had a corneal diameter of 10 mm or larger. Conclusions: Detailed ocular biometric analysis is crucial for optimizing both surgical outcomes and postoperative care in pediatric cataract patients. The positive correlations between CD, age and AL underline the importance of individualized surgical planning tailored to each patient's unique anatomical features. Additionally, our findings suggest that the use of a femtosecond laser is both feasible and safe for pediatric patients aged one year and older, potentially offering enhanced surgical precision and improved outcomes.}, } @article {pmid39200200, year = {2024}, author = {Yoo, JK and Kwon, SH and Yoon, SH and Lee, JE and Jeon, JE and Chung, JH and Lee, SY}, title = {Preservation of Vocal Function in Amyotrophic Lateral Sclerosis (ALS) Patients Following Percutaneous Dilatational Tracheostomy (PDT) and Adjuvant Therapies.}, journal = {Biomedicines}, volume = {12}, number = {8}, pages = {}, pmid = {39200200}, issn = {2227-9059}, abstract = {UNLABELLED: The study aimed to evaluate the efficacy of percutaneous dilatational tracheostomy (PDT) combined with adjuvant therapies in preserving vocal function in amyotrophic lateral sclerosis (ALS) patients.

METHODS: We performed a retrospective analysis of 47 ALS patients who underwent PDT at the Rodem Hospital from 2021 to 2023. Post-operatively, these patients were provided with a comprehensive treatment plan that included regenerative injection therapy, low-frequency electrical stimulation, respiratory rehabilitation, and swallowing rehabilitation therapy. Additionally, a balloon reduction program was implemented for effective tracheostomy tube (T-tube) management. The preservation of vocal functions was evaluated 4 weeks following the procedure.

RESULTS: While some patients maintained or slightly improved their ALSFRS-R speech scores, the overall trend indicated a decrease in speech scores post-PDT. This suggests that PDT in combination with adjuvant therapies may not universally improve vocal function, but can help maintain it in certain cases.

CONCLUSIONS: Our findings indicate that PDT combined with mesotherapy, low-frequency electrical stimulation, and swallowing rehabilitation therapy may play a role in maintaining vocal function in limb type ALS patients, though further research is needed to optimize patient management and to validate these results.}, } @article {pmid39200158, year = {2024}, author = {Zhao, M and Wang, J and Liu, M and Xu, Y and Huang, J and Zhang, Y and He, J and Gu, A and Liu, M and Liu, X}, title = {KIF1A, R1457Q, and P1688L Mutations Induce Protein Abnormal Aggregation and Autophagy Impairment in iPSC-Derived Motor Neurons.}, journal = {Biomedicines}, volume = {12}, number = {8}, pages = {}, pmid = {39200158}, issn = {2227-9059}, support = {2016YFC0905100//the National Key Research and Development Program of China/ ; 2021JJ30801//the Natural Science Foundation of Hunan Province, China/ ; kq2202077//the Natural Science Foundation of Changsha, China/ ; CX20230291//the Postgraduate Freedom Explo-ration Project of Central South University/ ; }, abstract = {Mutations in the C-terminal of KIF1A (Kinesin family member 1A) may lead to amyotrophic lateral sclerosis (ALS) through unknown mechanisms that are not yet understood. Using iPSC reprogramming technology and motor neuron differentiation techniques, we generated iPSCs from a healthy donor and two ALS patients with KIF1A mutations (R1457Q and P1688L) and differentiated them into spinal motor neurons (iPSC-MN) to investigate KIF1A-related ALS pathology. Our in vitro iPSC-iMN model faithfully recapitulated specific aspects of the disease, such as neurite fragmentation. Through this model, we observed that these mutations led to KIF1A aggregation at the proximal axon of motor neurons and abnormal accumulation of its transport cargo, LAMP1, resulting in autophagy dysfunction and cell death. RNAseq analysis also indicated that the functions of the extracellular matrix, structure, and cell adhesion were significantly disturbed. Notably, using rapamycin during motor neuron differentiation can effectively prevent motor neuron death.}, } @article {pmid39199527, year = {2024}, author = {Ail, BE and Ramele, R and Gambini, J and Santos, JM}, title = {An Intrinsically Explainable Method to Decode P300 Waveforms from EEG Signal Plots Based on Convolutional Neural Networks.}, journal = {Brain sciences}, volume = {14}, number = {8}, pages = {}, pmid = {39199527}, issn = {2076-3425}, support = {ITBACyT-2020//Instituto Tecnológico de Buenos Aires (ITBA)/ ; }, abstract = {This work proposes an intrinsically explainable, straightforward method to decode P300 waveforms from electroencephalography (EEG) signals, overcoming the black box nature of deep learning techniques. The proposed method allows convolutional neural networks to decode information from images, an area where they have achieved astonishing performance. By plotting the EEG signal as an image, it can be both visually interpreted by physicians and technicians and detected by the network, offering a straightforward way of explaining the decision. The identification of this pattern is used to implement a P300-based speller device, which can serve as an alternative communication channel for persons affected by amyotrophic lateral sclerosis (ALS). This method is validated by identifying this signal by performing a brain-computer interface simulation on a public dataset from ALS patients. Letter identification rates from the speller on the dataset show that this method can identify the P300 signature on the set of 8 patients. The proposed approach achieves similar performance to other state-of-the-art proposals while providing clinically relevant explainability (XAI).}, } @article {pmid39199512, year = {2024}, author = {Turner, N and Faull, C and Palmer, J and Armstrong, A and Bedford, J and Turner, MR and Wilson, E}, title = {Understanding Quality of Life for People with Motor Neurone Disease Who Use Tracheostomy Ventilation and Family Members: A Scoping Review.}, journal = {Brain sciences}, volume = {14}, number = {8}, pages = {}, pmid = {39199512}, issn = {2076-3425}, support = {Wilson/Oct21/968-794/MNDA_/Motor Neurone Disease Association/United Kingdom ; }, abstract = {Tracheostomy ventilation (TV) can increase survival time for people living with motor neurone disease (MND); however, the use of TV varies between countries. Concerns regarding anticipated quality of life (QoL) are among the reasons given by healthcare professionals for not recommending this intervention, yet little is known about QoL in this context. This scoping review was conducted to examine the evidence on QoL for those with MND who use TV and family members involved in their care. Using the methodological guidance of the Joanna Briggs Institute, 23 papers were identified for inclusion, and findings were inductively analysed to identify key themes. We found that people living with MND tend to rate QoL post TV more positively than anticipated by healthcare professionals or family members. QoL was found to be related to positive relationships and activities the person could maintain. Feeling able to make a choice and an adequate level of financial resources were also important factors. Family members tended to experience lower QoL, associated with the uncertainty surrounding an emergency procedure and the complexity of subsequently required care. More evidence on QoL from the perspectives of people with MND who use TV is needed to support decision making and inform guidance.}, } @article {pmid39199498, year = {2024}, author = {Kleinerova, J and McKenna, MC and Finnegan, M and Tacheva, A and Garcia-Gallardo, A and Mohammed, R and Tan, EL and Christidi, F and Hardiman, O and Hutchinson, S and Bede, P}, title = {Clinical, Cortical, Subcortical, and White Matter Features of Right Temporal Variant FTD.}, journal = {Brain sciences}, volume = {14}, number = {8}, pages = {}, pmid = {39199498}, issn = {2076-3425}, support = {JPND-Cofund-2-2019-1 & HRB EIA-2017-019//HRB/ ; }, abstract = {UNLABELLED: The distinct clinical and radiological characteristics of right temporal variant FTD have only been recently recognized.

METHODS: Eight patients with right temporal variant FTD were prospectively recruited and underwent a standardised neuropsychological assessment, clinical MRI, and quantitative neuroimaging.

RESULTS: Our voxelwise grey analyses captured bilateral anterior and mesial temporal grey matter atrophy with a clear right-sided predominance. Bilateral hippocampal involvement was also observed, as well as disease burden in the right insular and opercula regions. White matter integrity alterations were also bilateral in anterior temporal and sub-insular regions with a clear right-hemispheric predominance. Extra-temporal white matter alterations have also been observed in orbitofrontal and parietal regions. Significant bilateral but right-predominant thalamus, putamen, hippocampus, and amygdala atrophy was identified based on subcortical segmentation. The clinical profile of our patients was dominated by progressive indifference, decline in motivation, loss of interest in previously cherished activities, incremental social withdrawal, difficulty recognising people, progressive language deficits, increasingly rigid routines, and repetitive behaviours.

CONCLUSIONS: Right temporal variant FTD has an insidious onset and may be mistaken for depression at symptom onset. It manifests in a combination of apathy, language, and behavioural features. Quantitative MR imaging captures a characteristic bilateral but right-predominant temporal imaging signature with extra-temporal frontal and parietal involvement.}, } @article {pmid39199454, year = {2024}, author = {Calma, AD and van den Bos, M and Pavey, N and Santos Silva, C and Menon, P and Vucic, S}, title = {Physiological Biomarkers of Upper Motor Neuron Dysfunction in ALS.}, journal = {Brain sciences}, volume = {14}, number = {8}, pages = {}, pmid = {39199454}, issn = {2076-3425}, abstract = {Upper motor neuron (UMN) dysfunction is an important feature of amyotrophic lateral sclerosis (ALS) for the diagnosis and understanding of pathogenesis. The identification of UMN signs forms the basis of ALS diagnosis, although may be difficult to discern, especially in the setting of severe muscle weakness. Transcranial magnetic stimulation (TMS) techniques have yielded objective physiological biomarkers of UMN dysfunction in ALS, enabling the interrogation of cortical and subcortical neuronal networks with diagnostic, pathophysiological, and prognostic implications. Transcranial magnetic stimulation techniques have provided pertinent pathogenic insights and yielded novel diagnostic and prognostic biomarkers. Cortical hyperexcitability, as heralded by a reduction in short interval intracortical inhibition (SICI) and an increase in short interval intracortical facilitation (SICF), has been associated with lower motor neuron degeneration, patterns of disease evolution, as well as the development of specific ALS clinical features including the split hand phenomenon. Reduction in SICI has also emerged as a potential diagnostic aid in ALS. More recently, physiological distinct inhibitory and facilitatory cortical interneuronal circuits have been identified, which have been shown to contribute to ALS pathogenesis. The triple stimulation technique (TST) was shown to enhance the diagnostic utility of conventional TMS measures in detecting UMN dysfunction. Resting-state EEG is a novel neurophysiological technique developed for directly interrogating cortical neuronal networks in ALS, that have yielded potentially useful physiological biomarkers of UMN dysfunction. The present review discusses physiological biomarkers of UMN dysfunction in ALS, encompassing conventional and novel TMS techniques developed to interrogate the functional integrity of the corticomotoneuronal system, focusing on pathogenic, diagnostic, and prognostic utility.}, } @article {pmid39199265, year = {2024}, author = {Proaño, B and Benlloch, M and Sancho-Castillo, S and Privado, J and Bargues-Navarro, G and Sanchis-Sanchis, CE and Martínez Bolós, P and Carriquí-Suárez, AB and Cubero-Plazas, L and Platero Armero, JL and Escriva, D and Ceron, JJ and Tvarijonaviciute, A and de la Rubia Ortí, JE}, title = {Paraoxonase I Activity and Its Relationship with Nutrition in Amyotrophic Lateral Sclerosis.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {13}, number = {8}, pages = {}, pmid = {39199265}, issn = {2076-3921}, support = {2021-203-003//Catholic University of Valencia San Vicente Mártir/ ; }, abstract = {Background: Amyotrophic lateral sclerosis (ALS) is characterized by progressive motor neuron degeneration, with oxidative stress playing a key role. Paraoxonase 1 (PON1) is an antioxidant enzyme that may influence ALS progression. This study aimed to establish a predictive model for the influence of PON1 activity on functionality in ALS patients and explore its relationship with nutrition. Methods: In this observational cross-sectional study, 70 ALS patients underwent assessments of PON1 activity, lipid profile, functional capacity, respiratory function, and heart rate variability. A structural equation model was developed to determine the relationships between variables. Nutritional intake was analyzed in 65 patients. Results: The predictive model showed that PON1 activity and LDL levels positively influenced functionality, both directly and indirectly through respiratory capacity. Heart rate variability moderately predicted functionality independently. HDL levels were not significantly associated with functionality. Weak to moderate correlations were found between PON1 activity and intake of certain nutrients, with positive associations for monounsaturated fats and vitamin D, and negative associations for carbohydrates, proteins, and some micronutrients. Conclusions: PON1 activity appears to play an important role in ALS patient functionality, both directly and through effects on respiratory capacity. However, its relationship with nutritional intake was not strongly evident in this sample population.}, } @article {pmid39199129, year = {2024}, author = {Percio, A and Cicchinelli, M and Masci, D and Summo, M and Urbani, A and Greco, V}, title = {Oxidative Cysteine Post Translational Modifications Drive the Redox Code Underlying Neurodegeneration and Amyotrophic Lateral Sclerosis.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {13}, number = {8}, pages = {}, pmid = {39199129}, issn = {2076-3921}, abstract = {Redox dysregulation, an imbalance between oxidants and antioxidants, is crucial in the pathogenesis of various neurodegenerative diseases. Within this context, the "redoxome" encompasses the network of redox molecules collaborating to maintain cellular redox balance and signaling. Among these, cysteine-sensitive proteins are fundamental for this homeostasis. Due to their reactive thiol groups, cysteine (Cys) residues are particularly susceptible to oxidative post-translational modifications (PTMs) induced by free radicals (reactive oxygen, nitrogen, and sulfur species) which profoundly affect protein functions. Cys-PTMs, forming what is referred to as "cysteinet" in the redox proteome, are essential for redox signaling in both physiological and pathological conditions, including neurodegeneration. Such modifications significantly influence protein misfolding and aggregation, key hallmarks of neurodegenerative diseases such as Alzheimer's, Parkinson's, and notably, amyotrophic lateral sclerosis (ALS). This review aims to explore the complex landscape of cysteine PTMs in the cellular redox environment, elucidating their impact on neurodegeneration at protein level. By investigating specific cysteine-sensitive proteins and the regulatory networks involved, particular emphasis is placed on the link between redox dysregulation and ALS, highlighting this pathology as a prime example of a neurodegenerative disease wherein such redox dysregulation is a distinct hallmark.}, } @article {pmid39198773, year = {2024}, author = {Lei, Y and Zhang, X and Liu, H and Xu, Z and Xu, P}, title = {Amyotrophic lateral sclerosis associated with Sjögren's syndrome: a case report.}, journal = {BMC neurology}, volume = {24}, number = {1}, pages = {300}, pmid = {39198773}, issn = {1471-2377}, mesh = {Humans ; Male ; Middle Aged ; *Amyotrophic Lateral Sclerosis/complications/diagnosis/drug therapy/pathology ; *Sjogren's Syndrome/complications/diagnosis/drug therapy/pathology ; }, abstract = {BACKGROUND: Motor neuron disease (MND) is a chronic and progressive neurodegenerative disorder with an unknown cause. The development of amyotrophic lateral sclerosis (ALS) is believed to be linked to an immune response. Monocytes/macrophages and T cells are key players in the disease's advancement. Monitoring levels of cytokines in the blood can help forecast patient outcomes, while immunotherapy shows promise in alleviating symptoms for certain individuals.

CASE PRESENTATION: A 56-year-old male patient was admitted to the hospital due to progressive limb weakness persisting for eight months. The neurological examination revealed impairments in both upper and lower motor neurons, as well as sensory anomalies, without corresponding signs. Electrophysiological examination results indicated extensive neuronal damage and multiple peripheral nerve impairments, thereby the diagnosis was ALS. One month ago, the patient began experiencing symptoms of dry mouth and a bitter taste. Following tests for rheumatic immune-related antibodies and a lip gland biopsy, a diagnosis of Sjögren's syndrome (SS) was proposed. Despite treatment with medications such as hormones (methylprednisolone), immunosuppressants (hydroxychloroquine sulfate), and riluzole, the symptoms did not significantly improve, but also did not worsen.

CONCLUSION: It is recommended to include screening for SS in the standard assessment of ALS. Furthermore, research should focus on understanding the immune mechanisms involved in ALS, providing new insights for the diagnosis and treatment of ALS in conjunction with SS.}, } @article {pmid39197801, year = {2025}, author = {Zhan, Y and Huang, J and Tang, X and Du, B and Yang, B}, title = {Semen Strychni Pulveratum and vomicine alleviate neuroinflammation in amyotrophic lateral sclerosis through cGAS-STING-TBK1 pathway.}, journal = {Journal of ethnopharmacology}, volume = {336}, number = {}, pages = {118741}, doi = {10.1016/j.jep.2024.118741}, pmid = {39197801}, issn = {1872-7573}, mesh = {Animals ; *Protein Serine-Threonine Kinases/metabolism ; *Amyotrophic Lateral Sclerosis/drug therapy/metabolism ; Mice ; *Membrane Proteins/metabolism ; *Neuroprotective Agents/pharmacology/therapeutic use ; *Nucleotidyltransferases/metabolism ; Male ; Signal Transduction/drug effects ; Mice, Transgenic ; Neuroinflammatory Diseases/drug therapy ; Spinal Cord/drug effects/metabolism/pathology ; Disease Models, Animal ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fetal neuromuscular disorder characterized by the gradual deterioration of motor neurons. Semen Strychni pulveratum (SSP), a processed version of Semen Strychni (SS) powder, is widely used to treat ALS in China. Vomicine is one of the most primary components of SS. However, their pharmacological effects and mechanisms for ALS remain elusive.

AIM OF THE STUDY: This study aimed to evaluate the neuroprotective and anti-neuroinflammatory effects of SSP and vomicine, as well as to explore their protective roles in ALS and the underlying mechanisms.

MATERIALS AND METHODS: In vivo, 8-week-old hSOD1-WT mice and hSOD1-G93A mice were orally administered different concentrations of SSP (SSP-L = 5.46 mg/ml, SSP-M = 10.92 mg/ml or SSP-H = 16.38 mg/ml) once every other day for 8 weeks. A series of experiments, including body weight measurement, footprint tests, Hematoxylin & Eosin staining, and Nissl staining, were performed to evaluate the preventive effect of SSP. Immunofluorescence staining, western blotting, and RT-qPCR were subsequently performed to evaluate activation of the cGAS-STING-TBK1 pathway in the spinal cord. In vitro, hSOD1[G93A] NSC-34 cells were treated with vomicine to further explore the pharmacological mechanism of vomicine in the treatment of ALS via the cGAS-STING-TBK1 pathway.

RESULTS: SSP improved motor function, body weight loss, gastrocnemius muscle atrophy, and motor neuron loss in the spine and cortex of hSOD1-G93A mice. Furthermore, the cGAS-STING-TBK1 pathway was activated in the spinal cord of hSOD1-G93A mice, with activation predominantly observed in neurons and microglia. However, the levels of cGAS, STING, and pTBK1 proteins and cGAS, IRF3, IL-6, and IL-1β mRNA were reversed following intervention with SSP. Vomicine not only downregulated the levels of cGAS, TBK1, IL-6 and IFN-β mRNA, but also the levels of cGAS and STING protein in hSOD1[G93A] NSC-34 cells.

CONCLUSION: This study demonstrated that SSP and vomicine exert neuroprotective and anti-neuroinflammatory effects in the treatment of ALS. SSP and vomicine may reduce neuroinflammation by regulating the cGAS-STING-TBK1 pathway, and could thereby play a role in ALS treatment.}, } @article {pmid39197036, year = {2025}, author = {Sapaly, D and Cheguillaume, F and Weill, L and Clerc, Z and Biondi, O and Bendris, S and Buon, C and Slika, R and Piller, E and Sundaram, VK and da Silva Ramos, A and Amador, MDM and Lenglet, T and Debs, R and Le Forestier, N and Pradat, PF and Salachas, F and Lacomblez, L and Hesters, A and Borderie, D and Devos, D and Desnuelle, C and Rolland, AS and Periou, B and Vasseur, S and Chapart, M and Le Ber, I and Fauret-Amsellem, AL and Millecamps, S and Maisonobe, T and Leonard-Louis, S and Behin, A and Authier, FJ and Evangelista, T and Charbonnier, F and Bruneteau, G}, title = {Dysregulation of muscle cholesterol transport in amyotrophic lateral sclerosis.}, journal = {Brain : a journal of neurology}, volume = {148}, number = {3}, pages = {788-802}, pmid = {39197036}, issn = {1460-2156}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism/pathology/genetics ; Male ; *Cholesterol/metabolism ; Middle Aged ; Female ; *Muscle, Skeletal/metabolism/pathology ; Aged ; Adult ; Intracellular Signaling Peptides and Proteins ; Niemann-Pick C1 Protein ; Carrier Proteins/metabolism/genetics ; Biological Transport ; Vesicular Transport Proteins ; Muscle Fibers, Skeletal/metabolism ; Membrane Glycoproteins/metabolism/genetics ; Cells, Cultured ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder affecting motor neurons, with a typical lifespan of 3-5 years. Altered metabolism is a key feature of ALS that strongly influences prognosis, with an increase in whole body energy expenditure and changes in skeletal muscle metabolism, including greater reliance on fat oxidation. Dyslipidaemia has been described in ALS as part of the metabolic dysregulation, but its role in the pathophysiology of the disease remains controversial. Among the lipids, cholesterol is of particular interest as a vital component of cell membranes, playing a key role in signal transduction and mitochondrial function in muscle. The aim of this study was to investigate whether motor dysfunction in ALS might be associated with dysregulation of muscle cholesterol metabolism. We determined cholesterol content and analysed the expression of key determinants of the cholesterol metabolism pathway in muscle biopsies from 13 ALS patients and 10 asymptomatic ALS-mutation gene carriers compared to 16 control subjects. Using human control primary myotubes, we investigated the potential contribution of cholesterol dyshomeostasis to reliance on mitochondrial fatty acid. We found that cholesterol accumulates in the skeletal muscle of ALS patients and that cholesterol overload significantly correlates with disease severity evaluated by the Revised ALS Functional Rating Scale. These defects are associated with overexpression of the genes of the lysosomal cholesterol transporters Niemann-Pick type C1 (NPC1) and 2 (NPC2), which are required for cholesterol transfer from late endosomes/lysosomes to cellular membranes. Most notably, a significant increase in NPC2 mRNA levels could be detected in muscle samples from asymptomatic ALS-mutation carriers, long before disease onset. We found that filipin-stained unesterified cholesterol accumulated in the lysosomal compartment in ALS muscle samples, suggesting dysfunction of the NPC1/2 system. Accordingly, we report here that experimental NPC1 inhibition or lysosomal pH alteration in human primary myotubes was sufficient to induce the overexpression of NPC1 and NPC2 mRNA. Finally, acute NPC1 inhibition in human control myotubes induced a shift towards a preferential use of fatty acids, thus reproducing the metabolic defect characteristic of ALS muscle. We conclude that cholesterol homeostasis is dysregulated in ALS muscle from the presymptomatic stage. Targeting NPC1/2 dysfunction may be a new therapeutic strategy for ALS to restore muscle energy metabolism and slow motor symptom progression.}, } @article {pmid39196396, year = {2024}, author = {Radakovic, R and Carroll, A and Altiero, A and Reichwein, C and Walsh, S and Niven, E and Abrahams, S and Simmons, Z}, title = {Self-perceived quality of life, cognitive and behavioural impairment in amyotrophic lateral sclerosis.}, journal = {Journal of neurology}, volume = {271}, number = {10}, pages = {6822-6838}, pmid = {39196396}, issn = {1432-1459}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/psychology/complications/physiopathology ; Male ; *Quality of Life/psychology ; Female ; Middle Aged ; Cross-Sectional Studies ; Aged ; Cognitive Dysfunction/etiology/physiopathology/psychology ; Cohort Studies ; Self Concept ; Mental Disorders/psychology/etiology ; Adult ; }, abstract = {BACKGROUND: Self-perceived quality of life (QoL) is important in amyotrophic lateral sclerosis (ALS). Although caregiver burden and strain have been related to cognitive and behavioural impairment, there has been no comprehensive research looking at these impairments and how they may influence self-perceived QoL subdomains.

AIMS: To explore how cognitive and behavioural impairment are related to different areas of self-perceived QoL using disease-specific measures.

METHODS: This was a quantitative, cross-sectional, observational cohort study, utilising existing specialist ALS clinic data. Clinical and demographic variables were available as well as multidimensional measures, ALS-specific QoL Short Form (ALSsQoL-SF) results and the data from the Edinburgh Cognitive and Behavioural ALS Screen (ECAS). Group comparison and regression analyses were performed.

RESULTS: Data from 121 participants with ALS were analysed. 61.2% (N = 74) had either cognitive and/or behavioural impairment, with 28.9% (N = 35) with cognitive impairment (ALSci), 14.1% (N = 17) with behavioural impairment (ALSbi) and 18.2% (N = 22) with both (ALScbi). 38.8% (N = 47) were classified as having no impairments (ALSni). Those with ALSbi had significantly lower QoL in the domains of negative emotions and the interaction with people and the environment compared to those with ALSci and ALSni (ps < 0.05). Further, those with ALScbi had significantly lower QoL in the intimacy domains than those with ALSci and ALSni (ps < 0.05). Regression analysis showed specific cognitive and behavioural (inclusive of psychosis) predictors associated with specific QoL subdomains.

CONCLUSIONS: Behavioural impairments effect QoL in specific subdomains, namely relating to internalising (negative emotions) and externalising (interaction with people and the environment subdomains, intimacy).}, } @article {pmid39194682, year = {2024}, author = {Sacharczuk, M and Mickael, ME and Kubick, N and Kamińska, A and Horbańczuk, JO and Atanasov, AG and Religa, P and Ławiński, M}, title = {The Current Landscape of Hypotheses Describing the Contribution of CD4+ Heterogeneous Populations to ALS.}, journal = {Current issues in molecular biology}, volume = {46}, number = {8}, pages = {7846-7861}, pmid = {39194682}, issn = {1467-3045}, abstract = {Amyotrophic Lateral Sclerosis (ALS) is a poorly understood and fatal disease. It has a low prevalence and a 2-4 year survival period. Various theories and hypotheses relating to its development process have been proposed, albeit with no breakthrough in its treatment. Recently, the role of the adaptive immune system in ALS, particularly CD4+ T cells, has begun to be investigated. CD4+ T cells are a heterogeneous group of immune cells. They include highly pro-inflammatory types such as Th1 and Th17, as well as highly anti-inflammatory cells such as Tregs. However, the landscape of the role of CD4+ T cells in ALS is still not clearly understood. This review covers current hypotheses that elucidate how various CD4+ T cells can contribute to ALS development. These hypotheses include the SWITCH model, which suggests that, in the early stages of the disease, Tregs are highly capable of regulating the immune response. However, in the later stages of the disease, it seems that pro-inflammatory cells such as Th1 and Th17 are capable of overwhelming Treg function. The reason why this occurs is not known. Several research groups have proposed that CD4+ T cells as a whole might experience aging. Others have proposed that gamma delta T cells might directly target Tregs. Additionally, other research groups have argued that less well-known CD4+ T cells, such as Emoes+ CD4+ T cells, may be directly responsible for neuron death by producing granzyme B. We propose that the ALS landscape is highly complicated and that there is more than one feasible hypothesis. However, it is critical to take into consideration the differences in the ability of different populations of CD4+ T cells to infiltrate the blood-brain barrier, taking into account the brain region and the time of infiltration. Shedding more light on these still obscure factors can help to create a personalized therapy capable of regaining the balance of power in the battle between the anti-inflammatory and pro-inflammatory cells in the central nervous system of ALS patients.}, } @article {pmid39193833, year = {2025}, author = {Jalaiei, A and Asadi, MR and Daneshmandpour, Y and Rezazadeh, M and Ghafouri-Fard, S}, title = {Clinical, molecular, physiologic, and therapeutic feature of patients with CHRNA4 and CHRNB2 deficiency: A systematic review.}, journal = {Journal of neurochemistry}, volume = {169}, number = {1}, pages = {e16200}, doi = {10.1111/jnc.16200}, pmid = {39193833}, issn = {1471-4159}, mesh = {Humans ; *Receptors, Nicotinic/genetics ; Mutation/genetics ; Neurodegenerative Diseases/genetics/metabolism ; }, abstract = {The α4β2 nAChRs are crucial ion channels that control neurotransmitter release and play a role in various physiologic and pathologic processes. CHRNA4 encodes the α4-nAChRs, while CHRNB2 encodes the β2-nAChRs. Recent studies have found different variants of α4β2-nAChRs in individuals with conditions such as AD, ADHD, ALS, PD, and brain abnormalities. We conducted a scoping review following a six-stage methodology structure and adhering to PRISMA guidelines. We systematically reviewed articles using relevant keywords up to October 2, 2023. In this summary, we cover the clinical symptoms reported, the genes and protein structure of CHRNA4 and CHRNB2, mutations in these genes, inheritance patterns, the functional impact of mutations and polymorphisms in CHRNA4 and CHRNB2, and the epidemiology of these diseases. Recent research indicates that nAChRs may play a significant role in neurodegenerative disorders, possibly impacting neuronal function through yet undiscovered regulatory pathways. Studying how nAChRs interact with disease-related aggregates in neurodegenerative conditions may lead to new treatment options for these disorders.}, } @article {pmid39193573, year = {2024}, author = {Soresi, M and Giannitrapani, L}, title = {Glucagon-like peptide 1 agonists are potentially useful drugs for treating metabolic dysfunction-associated steatotic liver disease.}, journal = {World journal of gastroenterology}, volume = {30}, number = {30}, pages = {3541-3547}, pmid = {39193573}, issn = {2219-2840}, mesh = {Humans ; *Non-alcoholic Fatty Liver Disease/drug therapy/pathology/metabolism ; *Glucagon-Like Peptides/therapeutic use ; Liver/drug effects/pathology/metabolism ; Insulin Resistance ; Drug Therapy, Combination/methods ; Glucagon-Like Peptide 1/agonists/metabolism ; Treatment Outcome ; Hypoglycemic Agents/therapeutic use/pharmacology ; Disease Progression ; Incretins/therapeutic use ; *Glucagon-Like Peptide-1 Receptor Agonists ; }, abstract = {In this editorial, we comment on Yin et al's recently published Letter to the editor. In particular, we focus on the potential use of glucagon-like peptide 1 receptor agonists (GLP-1RAs) alone, but even more so in combination therapy, as one of the most promising therapies in metabolic dysfunction-associated steatotic liver disease (MASLD), the new definition of an old condition, non-alcoholic fatty liver disease, which aims to better define the spectrum of steatotic pathology. It is well known that GLP-1RAs, having shown outstanding performance in fat loss, weight loss, and improvement of insulin resistance, could play a role in protecting the liver from progressive damage. Several clinical trials have shown that, among GLP-1RAs, semaglutide is a safe, well-studied therapeutic choice for MASLD patients; however, most studies demonstrate that, while semaglutide can reduce steatosis, including steatohepatitis histological signs (in terms of inflammatory cell infiltration and hepatocyte ballooning), it does not improve fibrosis. Combinations of therapies with different but complementary mechanisms of action are considered the best way to improve efficiency and slow disease progression due to the complex pathophysiology of the disease. In particular, GLP-1RAs associated with antifibrotic drug therapy, dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1RA or GLP-1 and glucagon RAs have promoted greater improvement in hepatic steatosis, liver biochemistry, and non-invasive fibrosis tests than monotherapy. Therefore, although to date there are no definitive indications from international drug agencies, there is the hope that soon the therapeutic lines in the most advanced phase of study will be able to provide a therapy for MASLD, one that will certainly include the use of GLP-1RAs as combination therapy.}, } @article {pmid39193017, year = {2024}, author = {Chen, X and Cai, L and Fan, W and Yang, Q and Mao, X and Yao, L}, title = {Causal relationships between rheumatoid arthritis and neurodegenerative diseases: a two-sample univariable and multivariable Mendelian randomization study.}, journal = {Frontiers in medicine}, volume = {11}, number = {}, pages = {1439344}, pmid = {39193017}, issn = {2296-858X}, abstract = {BACKGROUND: Observational research has highlighted a potential relationship between rheumatoid arthritis (RA) and neurodegenerative diseases (NDs). However, the confirmation of a causal connection is impeded by the inherent limitations of such studies, including vulnerability to confounding factors and the possibility of reverse causality. This study employs a two-sample Mendelian randomization (MR) approach to assess the causal impact of RA on three NDs, including Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS).

METHODS: We aggregated data from genome-wide association studies (GWASs) targeting RA or NDs within populations of European descent. Single nucleotide polymorphisms (SNPs) with robust associations to RA were identified as instrumental variables (IVs). To estimate the association between RA and AD, PD, and ALS, we utilized the inverse variance weighted (IVW) method in our univariable MR (UVMR) analysis. Validation of the IVW results ensued through supplementary analyses using MR-Egger and weighted median methods. The multivariable MR (MVMR) analysis was conducted, adjusting for body mass index (BMI), alcohol drinking, and type 2 diabetes mellitus (T2DM).

RESULTS: The UVMR analysis, based on the IVW method, revealed a significantly positive causal association between RA and late-onset (LO) AD (OR [95% CI] = 1.084 [1.020-1.153]; p = 9.980 × 10[-3]), while suggesting a possible inverse relationship with PD (OR [95% CI] = 0.727 [0.563-0.938]; p = 0.014). Our study did not detect any causal connections between RA and early-onset (EO) AD, atypical or mixed (AM) AD, and ALS (all p > 0.05). The MVMR analysis results indicated that after adjusting for alcohol drinking, RA remains a risk factor for LOAD (OR [95% CI] = 1.094 [1.024-1.169]; p = 0.008). However, MVMR analysis revealed no causal connections between RA and PD after adjustments for BMI, alcohol drinking, or T2DM (all p > 0.05). Sensitivity analyses showed no evidence of heterogeneity and horizontal pleiotropy.

CONCLUSIONS: This research provides genetic evidence indicating that RA potentially causes an increased risk of developing LOAD and PD. Such a revelation underscores the importance for individuals suffering from RA to be vigilant about the potential emergence of LOAD and PD. Ongoing monitoring and prompt detection are essential for successfully managing and intervening in this possible risk.}, } @article {pmid39192891, year = {2024}, author = {Murtazina, A and Subbotin, D and Kuchina, A and Gilvanova, O and Degterev, D and Shchagina, O and Cherevatova, T and Bulakh, M and Sherstyukova, D and Ryzhkova, O and Kurushina, O and Skoblov, M and Borovikov, A and Kutsev, S}, title = {Asymmetric scapuloperoneal phenotype of MATR3-related distal myopathy: case series.}, journal = {Frontiers in genetics}, volume = {15}, number = {}, pages = {1414928}, pmid = {39192891}, issn = {1664-8021}, abstract = {Recent research has sparked a discussion on the spectrum of diseases linked to the MATR3 gene associated with amyotrophic lateral sclerosis and distal myopathy with vocal cord and pharyngeal weakness (VCPDM). To date, fewer than 50 cases of VCPDM have been reported in the literature. We aim to build upon the work of previous researchers by gathering additional information about VCPDM. In this study, we present six patients from four unrelated families affected by VCPDM. Our observations include patients exhibiting both the typical phenotype associated with MATR3-related distal myopathy and rare symptomatic manifestations of the disease. Notably, two cases presented with an asymmetric scapuloperoneal phenotype, leading in one case to an initial misdiagnosis of facioscapulohumeral muscular dystrophy.}, } @article {pmid39192797, year = {2024}, author = {Luo, RC and Wu, XY and Yu, WW and Zheng, YJ and Wang, D}, title = {[Research progress on the relationship between TRAF6 and neurodegenerative diseases].}, journal = {Sheng li xue bao : [Acta physiologica Sinica]}, volume = {76}, number = {4}, pages = {653-662}, pmid = {39192797}, issn = {0371-0874}, mesh = {Animals ; Humans ; Alzheimer Disease/metabolism/etiology ; Amyotrophic Lateral Sclerosis/metabolism/physiopathology/genetics/etiology ; Multiple Sclerosis/metabolism/physiopathology/etiology ; *Neurodegenerative Diseases/metabolism/etiology ; Parkinson Disease/metabolism/physiopathology ; *TNF Receptor-Associated Factor 6/metabolism/genetics/physiology ; Ubiquitination ; }, abstract = {Given the increasing trend of aging population in the world, neurodegenerative diseases (NDDs), a common type of diseases that mostly occur in the elderly, have attracted much more attention. It has been shown that tumor necrosis factor receptor-associated factor 6 (TRAF6) is involved in the regulation of neuroinflammation, an important pathological feature of NDDs, and affects the occurrence and development of NDDs. Most importantly, the regulatory effect of TRAF6 is related to its ubiquitination. Therefore, in the present paper, the molecular structure, biological function, and ubiquitination mechanism of TRAF6, and its relationship with some common NDDs, including Alzheimer's disease, Parkinson's disease, multiple sclerosis, and amyotrophic lateral sclerosis, were analyzed and summarized. The possible molecular mechanisms by which TRAF6 regulates the occurrence of NDDs were also elucidated, providing a theoretical basis for exploring the etiology and treatment of NDDs.}, } @article {pmid39192497, year = {2024}, author = {Lee, I and Garret, MA and Wuu, J and Harrington, EA and Berry, JD and Miller, TM and Harms, M and Benatar, M and Shneider, N}, title = {Body mass index is lower in asymptomatic C9orf72 expansion carriers but not in SOD1 pathogenic variant carriers compared to gene negatives.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {25}, number = {7-8}, pages = {672-679}, pmid = {39192497}, issn = {2167-9223}, support = {K23 NS131586/NS/NINDS NIH HHS/United States ; R01 NS105479/NS/NINDS NIH HHS/United States ; U54 NS092091/NS/NINDS NIH HHS/United States ; }, mesh = {Humans ; Male ; Female ; *Amyotrophic Lateral Sclerosis/genetics/diagnosis ; *C9orf72 Protein/genetics ; *Body Mass Index ; *Superoxide Dismutase-1/genetics ; Middle Aged ; *Heterozygote ; Adult ; Cohort Studies ; Genotype ; DNA Repeat Expansion/genetics ; Aged ; }, abstract = {Objective: To examine the relationship between body mass index (BMI) and genotype among pre-symptomatic carriers of different pathogenic variants associated with amyotrophic lateral sclerosis. Methods: C9orf72+ carriers, SOD1+ carriers, and pathogenic variant negative controls (Gene-Negatives) were included from 3 largely independent cohorts: ALS Families Project (ALS-Families); Dominantly inherited ALS (DIALS); and Pre-symptomatic Familial ALS (Pre-fALS). First reported (ALS-Families) or measured (DIALS and Pre-fALS) weight and height were used to calculate BMI. Age at weight measurement, self-reported sex (male vs. female), and highest education (high school or below vs. college education vs. graduate school or above) were extracted. The associations between BMI and genotype in each cohort were examined with multivariable linear regression models, adjusted for age, sex, and education. Results: A total of 223 C9orf72+ carriers, 135 SOD1+ carriers, and 191 Gene-Negatives were included, deriving from ALS-Families (n = 114, median age 46, 37% male), DIALS (n = 221, median age 46, 30% male), and Pre-fALS (n = 214, median age 44, 39% male). Adjusting for age, sex, and education, the mean BMI of C9orf72+ carriers was lower than Gene-Negatives by 2.4 units (95% confidence interval [CI] = 0.3-4.6, p = 0.02) in ALS-Families; 2.7 units (95% CI = 0.9-4.4, p = 0.003) in DIALS; and 1.9 units (95% CI = 0.5-4.2, p = 0.12) in Pre-fALS. There were no significant differences in BMI between SOD1+ carriers and Gene-Negatives in any of the 3 cohorts. Conclusions: Compared to Gene-Negatives, average BMI is lower in asymptomatic C9orf72+ carriers across 3 cohorts while no significant difference was found between Gene-Negatives and SOD1+ carriers.}, } @article {pmid39192451, year = {2024}, author = {Yan, Y and Huang, SY and Feng, YJ and Zhao, CY and Sheng, GX and Chen, J and Jiang, JJ and Gao, F and Mao, SS}, title = {[Pediatric amyotrophic lateral sclerosis caused by FUS gene variation in 2 cases].}, journal = {Zhonghua er ke za zhi = Chinese journal of pediatrics}, volume = {62}, number = {9}, pages = {893-895}, doi = {10.3760/cma.j.cn112140-20240315-00184}, pmid = {39192451}, issn = {0578-1310}, mesh = {Female ; Humans ; *Amyotrophic Lateral Sclerosis/genetics ; DNA Mutational Analysis ; Exons ; Fatal Outcome ; Heterozygote ; *Mutation ; *RNA-Binding Protein FUS/genetics ; Child ; Adolescent ; }, } @article {pmid39191336, year = {2024}, author = {Sirtori, CR and Castiglione, S and Pavanello, C}, title = {Metformin: From diabetes to cancer to prolongation of life.}, journal = {Pharmacological research}, volume = {208}, number = {}, pages = {107367}, doi = {10.1016/j.phrs.2024.107367}, pmid = {39191336}, issn = {1096-1186}, mesh = {Humans ; *Metformin/therapeutic use/pharmacology ; Animals ; *Neoplasms/drug therapy/metabolism ; *Hypoglycemic Agents/therapeutic use/pharmacology ; *Diabetes Mellitus/drug therapy/metabolism ; Longevity/drug effects ; Antineoplastic Agents/therapeutic use/pharmacology ; }, abstract = {The metformin molecule dates back to over a century, but its clinical use started in the '50s. Since then, its use in diabetics has grown constantly, with over 150 million users today. The therapeutic profile also expanded, with improved understanding of novel mechanisms. Metformin has a major activity on insulin resistance, by acting on the insulin receptors and mitochondria, most likely by activation of the adenosine monophosphate-activated kinase. These and associated mechanisms lead to significant lipid lowering and body weight loss. An anti-cancer action has come up in recent years, with mechanisms partly dependent on the mitochondrial activity and also on phosphatidylinositol 3-kinase resistance occurring in some malignant tumors. The potential of metformin to raise life-length is the object of large ongoing studies and of several basic and clinical investigations. The present review article will attempt to investigate the basic mechanisms behind these diverse activities and the potential clinical benefits. Metformin may act on transcriptional activity by histone modification, DNA methylation and miRNAs. An activity on age-associated inflammation (inflammaging) may occur via activation of the nuclear factor erythroid 2 related factor and changes in gut microbiota. A senolytic activity, leading to reduction of cells with the senescent associated secretory phenotype, may be crucial in lifespan prolongation as well as in ancillary properties in age-associated diseases, such as Parkinson's disease. Telomere prolongation may be related to the activity on mitochondrial respiratory factor 1 and on peroxisome gamma proliferator coactivator 1-alpha. Very recent observations on the potential to act on the most severe neurological disorders, such as amyotrophic lateral sclerosis and frontotemporal dementia, have raised considerable hope.}, } @article {pmid39191178, year = {2024}, author = {Ruotolo, G and D'Anzi, A and Giovenale, AMG and Giacometti, C and Ferrari, D and Vulcano, E and D'Asdia, C and Lattante, S and Sabatelli, M and Codazzi, F and Consalez, G and Marano, M and Di Lazzaro, V and Pennuto, M and Vescovi, A and Rosati, J}, title = {Induced pluripotent stem cell production (CSSi019-A)(14432) from an asymptomatic subject carrying a expansion of C9orf72 gene.}, journal = {Stem cell research}, volume = {81}, number = {}, pages = {103540}, doi = {10.1016/j.scr.2024.103540}, pmid = {39191178}, issn = {1876-7753}, mesh = {*Induced Pluripotent Stem Cells/metabolism ; Humans ; *C9orf72 Protein/genetics/metabolism ; Aged ; Amyotrophic Lateral Sclerosis/genetics/pathology/metabolism ; DNA Repeat Expansion ; Male ; Female ; }, abstract = {One of the genetic mutations most associated with the onset of amyotrophic lateral sclerosis, both in sporadic and familial cases, is the expansion of the C9orf72 gene. The presence of more than 30 repeats (GGGGCC) correlates with uncertain ALS symptomatology. Here we collected a dermal biopsy from a subject carrying 36 hexanucleotide repeats and reprogrammed it into an induced pluripotent stem cell line. Despite the number of repeat elements, the subject had no symptoms at the age of the biopsy (76 years), thus resulting in a healthy carrier of the mutation.}, } @article {pmid39191031, year = {2024}, author = {He, Q and Wang, Y and Zhao, F and Wei, S and Li, X and Zeng, G}, title = {APE1: A critical focus in neurodegenerative conditions.}, journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie}, volume = {179}, number = {}, pages = {117332}, doi = {10.1016/j.biopha.2024.117332}, pmid = {39191031}, issn = {1950-6007}, mesh = {Humans ; *Neurodegenerative Diseases/metabolism ; *DNA-(Apurinic or Apyrimidinic Site) Lyase/metabolism ; Animals ; }, abstract = {The global growth of the aging population has resulted in an increased prevalence of neurodegenerative diseases, characterized by the progressive loss of central nervous system (CNS) structure and function. Given the high incidence and debilitating nature of neurodegenerative diseases, there is an urgent need to identify potential biomarkers and novel therapeutic targets thereof. Apurinic/apyrimidinic endonuclease 1 (APE1), has been implicated in several neurodegenerative diseases, as having a significant role. Abnormal APE1 expression has been observed in conditions including Alzheimer's disease, stroke, amyotrophic lateral sclerosis, Parkinson's disease, Huntington's disease, and epilepsy. However, whether this dysregulation is protective or harmful remains unclear. This review aims to comprehensively review the current understanding of the involvement of APE1 in neurodegenerative diseases.}, } @article {pmid39190906, year = {2024}, author = {Yu, J and Chen, S and Zhang, H and Zhang, S and Dong, D}, title = {Patterns of the Health and Economic Burden of 33 Rare Diseases in China: Nationwide Web-Based Study.}, journal = {JMIR public health and surveillance}, volume = {10}, number = {}, pages = {e57353}, pmid = {39190906}, issn = {2369-2960}, mesh = {Humans ; China/epidemiology ; *Rare Diseases/epidemiology/economics ; Male ; Adult ; Female ; Cross-Sectional Studies ; Middle Aged ; *Cost of Illness ; Adolescent ; Child ; *Internet ; Child, Preschool ; Young Adult ; Surveys and Questionnaires ; Aged ; Infant ; }, abstract = {BACKGROUND: Rare diseases (RDs) affect millions of individuals collectively worldwide, contributing to significant burdens on patients and families in various aspects. However, there is a lack of evidence on the underlying patterns of burdens among diverse RDs for informing targeted social and health policies to address the unmet needs of this vulnerable population.

OBJECTIVE: This study aimed to examine the underlying patterns of the health and economic burden of 33 different RDs in China and identify the potential determinants.

METHODS: A nationwide internet-based cross-sectional survey was conducted in China between 2019 and 2020. Physical and mental health burden was measured by health-related quality of life. Economic burden was evaluated based on the proportions of direct medical, direct nonmedical, and indirect costs relative to household income. We used cluster analysis to identify patterns of health and economic burdens and conducted multinomial logistic regression to explore potential predictors of cluster membership.

RESULTS: The study included 8454 adults and 8491 children affected by 33 RDs. The following 3 clusters were identified: "extremely high burden" (representing 92/8454, 1.1% and 19/8491, 0.2% of adult and pediatric patients, respectively), "overall high burden" (5933/8454, 70.2% and 4864/8491, 57.3%, respectively), and "overall low burden" (2429/8454, 28.7% and 3608/8491, 42.5%, respectively). Wilson disease, Marfan syndrome, and Langerhans cell histiocytosis more likely resulted in an "extremely high burden" than others. Poverty was significantly associated with being in this extremely high burden group. Diseases causing neuromuscular symptoms and requiring long-term treatment (eg, amyotrophic lateral sclerosis, spinocerebellar ataxia, and Dravet syndrome) were prevalent in the "overall high burden" group. Key predictors of this group included older age, lower socioeconomic status, diagnostic delay, and comorbidity.

CONCLUSIONS: This study provides novel and valuable evidence on the burden of RDs in developing regions like China. The findings reveal significant disparities in the impact of RDs, emphasizing the need for targeted health care interventions and policies.}, } @article {pmid39190080, year = {2024}, author = {Jensen, BK}, title = {Astrocyte-Neuron Interactions Contributing to Amyotrophic Lateral Sclerosis Progression.}, journal = {Advances in neurobiology}, volume = {39}, number = {}, pages = {285-318}, pmid = {39190080}, issn = {2190-5215}, mesh = {*Amyotrophic Lateral Sclerosis/metabolism/pathology ; Humans ; *Astrocytes/metabolism ; *Disease Progression ; *Motor Neurons/metabolism/pathology ; *Cell Communication/physiology ; Animals ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a complex disease impacting motor neurons of the brain, brainstem, and spinal cord. Disease etiology is quite heterogeneous with over 40 genes causing the disease and a vast ~90% of patients having no prior family history. Astrocytes are major contributors to ALS, particularly through involvement in accelerating disease progression. Through study of genetic forms of disease including SOD1, TDP43, FUS, C9orf72, VCP, TBK1, and more recently patient-derived cells from sporadic individuals, many biological mechanisms have been identified to cause intrinsic or glial-mediated neurotoxicity to motor neurons. Overall, many of the normally supportive and beneficial roles that astrocytes contribute to neuronal health and survival instead switch to become deleterious and neurotoxic. While the exact pathways may differ based on disease-origin, altered astrocyte-neuron communication is a common feature of ALS. Within this chapter, distinct genetic forms are examined in detail, along with what is known from sporadic patient-derived cells. Overall, this chapter highlights the interplay between astrocytes and neurons in this complex disease and describes the key features underlying: astrocyte-mediated motor neuron toxicity, excitotoxicity, oxidative/nitrosative stress, protein dyshomeostasis, metabolic imbalance, inflammation, trophic factor withdrawal, blood-brain/blood-spinal cord barrier involvement, disease spreading, and the extracellular matrix/cell adhesion/TGF-β signaling pathways.}, } @article {pmid39189114, year = {2024}, author = {Rivera Flores, IV and Monopoli, K and Jackson, S and Echeverria, D and O'Reilly, D and Brown, RH and Khvorova, A}, title = {Near Sequence Homology Does Not Guarantee siRNA Cross-Species Efficacy.}, journal = {Nucleic acid therapeutics}, volume = {34}, number = {5}, pages = {234-244}, pmid = {39189114}, issn = {2159-3345}, support = {R01 NS104022/NS/NINDS NIH HHS/United States ; S10 OD020012/OD/NIH HHS/United States ; T32 GM135751/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; *RNA, Small Interfering/genetics/chemistry ; Humans ; Dogs ; Mice ; Rats ; *Superoxide Dismutase-1/genetics ; *Species Specificity ; Sheep ; Base Pair Mismatch/genetics ; Cell Line ; }, abstract = {Small interfering RNAs (siRNAs) represent a novel class of drugs capable of potent and sustained modulation of genes across various tissues. Preclinical development of siRNAs necessitates assessing efficacy and toxicity in animal models. While identifying therapeutic leads with cross-species activity can expedite development, it may compromise efficacy and be infeasible for certain gene targets. Here, we investigate whether deriving species-active siRNAs from potent human-targeting leads-an approach termed mismatch conversion-can yield potent compounds. We systematically altered potent siRNAs targeting human genes associated with diseases-SOD1 (ALS), JAK1 (inflammation), and HTT (HD)-to generate species-matching variants with full complementarity to their target in NHPs, mice, rats, sheep, and dogs. Variants potency and efficacy were measured in corresponding cell lines. We demonstrate that sequence, position, and number of mismatches significantly influence the ability to generate potent species-active compounds via mismatch conversion. Across tested sequences, mismatch conversion strategy ability to identify a species-active lead varied from 0% to 70%. For SOD1, lead compounds identified from species-focus screening in mouse and dog cells were more potent than leads obtained from mismatch conversion. Thus, a focused screening of therapeutic lead and model compounds may represent a more reliable strategy for the clinical advancement of siRNAs.}, } @article {pmid39188590, year = {2024}, author = {Roca-Pereira, S and Domínguez, R and Moreno León, I and Colomina, MJ and Martínez Yélamos, A and Martínez Yélamos, S and Povedano, M and Andrés-Benito, P}, title = {Increased CXCL12, a potential CSF biomarker for differential diagnosis of amyotrophic lateral sclerosis.}, journal = {Brain communications}, volume = {6}, number = {4}, pages = {fcae271}, pmid = {39188590}, issn = {2632-1297}, abstract = {Amyotrophic lateral sclerosis is a debilitating and lethal neurodegenerative disorder marked by the gradual deterioration of motor neurons. Diagnosing amyotrophic lateral sclerosis is challenging due to the lack of reliable diagnostic tools, with clinical assessment being the primary criterion. Recently, increased levels of neurofilament light chain in CSF have been considered a useful biomarker in disease, correlating with disease progression but not specific for diagnosis. This study utilized enzyme-linked immunosorbent assay to measure CSF C-X-C motif chemokine ligand 12 levels in healthy controls, amyotrophic lateral sclerosis patients and patients with amyotrophic lateral sclerosis-mimic disorders, assessing its potential as a diagnostic biomarker and comparing it with neurofilament light chain levels. Our results confirmed previous findings, showing increased C-X-C motif chemokine ligand 12 levels in amyotrophic lateral sclerosis patients compared to healthy control (797.07 ± 31.84 pg/mL versus 316.15 ± 16.6 pg/mL; P = 0.000) and increased CSF neurofilament light chain levels in amyotrophic lateral sclerosis (4565.63 ± 263.77 pg/mL) compared to healthy control (847.86 ± 214.37 pg/mL; P = 0.000). Increased C-X-C motif chemokine ligand levels were specific to amyotrophic lateral sclerosis, not seen in amyotrophic lateral sclerosis-mimic conditions like myelopathies (252.20 ± 23.16 pg/mL; P = 0.000), inflammatory polyneuropathies (270.24 ± 32.23 pg/mL; P = 0.000) and other mimic diseases (228.91 ± 29.20 pg/mL; P = 0.000). In contrast, CSF neurofilament light chain levels in amyotrophic lateral sclerosis overlapped with those in myelopathies (2900.11 ± 872.20 pg/mL; P = 0.821) and other mimic diseases (3169.75 ± 1096.65 pg/mL; P = 0.63), but not with inflammatory polyneuropathies (1156.4 ± 356.6 pg/mL; P = 0.000). Receiver operating characteristic curve analysis indicated significant differences between the area under the curve values of C-X-C motif chemokine ligand and neurofilament light chain in their diagnostic capacities. C-X-C motif chemokine ligand could differentiate between amyotrophic lateral sclerosis and myelopathies (area under the curve 0.99 ± 0.005), inflammatory polyneuropathies (area under the curve 0.962 ± 0.027) and other mimic diseases (area under the curve 1.00 ± 0.00), whereas neurofilament light chain was only effective in inflammatory polyneuropathies cases (area under the curve 0.92 ± 0.048), not in myelopathies (area under the curve 0.71 ± 0.09) or other mimic diseases (area under the curve 0.69 ± 0.14). We also evaluated C-X-C motif chemokine ligand levels in plasma [amyotrophic lateral sclerosis (2022 ± 81.8 pg/mL) versus healthy control (1739.43 ± 77.3 pg/mL; P = 0.015)] but found CSF determination (area under the curve 0.97 ± 0.012) to be more accurate than plasma determination (area under the curve 0.65 ± 0.063). In plasma, single molecule array (SIMOA) neurofilament light chain determination [amyotrophic lateral sclerosis (86.00 ± 12.23 pg/mL) versus healthy control (12.69 ± 1.15 pg/mL); P = 0.000] was more accurate than plasma C-X-C motif chemokine ligand 12 (area under the curve 0.98 ± 0.01405). These findings suggest that CSF C-X-C motif chemokine ligand 12 levels can enhance diagnostic specificity in distinguishing amyotrophic lateral sclerosis from amyotrophic lateral sclerosis-mimic disorders, compared to neurofilament light chain. Larger studies are needed to validate these results, but C-X-C motif chemokine ligand 12 determination shows promising diagnostic potential.}, } @article {pmid39187524, year = {2024}, author = {Femiano, C and Bruno, A and Gilio, L and Buttari, F and Dolcetti, E and Galifi, G and Azzolini, F and Borrelli, A and Furlan, R and Finardi, A and Musella, A and Mandolesi, G and Storto, M and Centonze, D and Stampanoni Bassi, M}, title = {Inflammatory signature in amyotrophic lateral sclerosis predicting disease progression.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {19796}, pmid = {39187524}, issn = {2045-2322}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/cerebrospinal fluid/diagnosis ; Female ; Male ; *Disease Progression ; Middle Aged ; *Cytokines/cerebrospinal fluid ; *Biomarkers/cerebrospinal fluid ; Cross-Sectional Studies ; Aged ; Inflammation/cerebrospinal fluid ; Principal Component Analysis ; Adult ; Prognosis ; Case-Control Studies ; }, abstract = {Experimental studies identified a role of neuroinflammation in the pathogenesis of neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). However, the role of inflammatory molecules as diagnostic and prognostic biomarkers in patients with ALS is unclear. In this cross-sectional study, the cerebrospinal fluid (CSF) levels of a set of inflammatory cytokines and chemokines were analyzed in 56 newly diagnosed ALS patients and in 47 age- and sex-matched control patients without inflammatory or degenerative neurological disorders. The molecules analyzed included: interleukin (IL)-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12, IL-13, IL-17, granulocyte colony stimulating factor (GCSF), macrophage inflammatory protein (MIP)-1a, MIP-1b, tumor necrosis factors (TNF), eotaxin. Principal component analysis (PCA) was used to explore possible associations between CSF molecules and ALS diagnosis. In addition, we analyzed the association between CSF cytokine profiles and clinical characteristics, including the disease progression rate score, and peripheral inflammation assessed using the Neutrophil-to-lymphocyte ratio (NLR). PCA identified six principal components (PCs) explaining 70.67% of the total variance in the CSF cytokine set. The principal component (PC1) explained 26.8% of variance and showed a positive load with CSF levels of IL-9, IL-4, GCSF, IL-7, IL-17, IL-13, IL-6, IL-1β, TNF, and IL-2. Logistic regression showed a significant association between PC1 and ALS diagnosis. In addition, in ALS patients, the same component was significantly associated with higher disease progression rate score and positively correlated with NLR. CSF inflammatory activation in present in ALS at the time of diagnosis and may characterize patients at higher risk for disease progression.}, } @article {pmid39187240, year = {2025}, author = {Lenz, M and Egenolf, P and Menzhausen, J and Heck, V and Perera, A and Eysel, P and Scheyerer, M and Oikonomidis, S}, title = {Clinical Outcome after Endoscopic Facet Denervation in Patients with Chronic Low Back Pain.}, journal = {Zeitschrift fur Orthopadie und Unfallchirurgie}, volume = {163}, number = {2}, pages = {167-175}, doi = {10.1055/a-2348-1186}, pmid = {39187240}, issn = {1864-6743}, mesh = {Humans ; *Low Back Pain/surgery/diagnosis ; Male ; Female ; *Zygapophyseal Joint/surgery/innervation ; *Denervation/methods ; Middle Aged ; Treatment Outcome ; Retrospective Studies ; Adult ; Aged ; *Chronic Pain/surgery/diagnosis ; *Endoscopy/methods ; Pain Measurement ; Risk Factors ; }, abstract = {In mehreren Studien wurde berichtet, dass Kreuzschmerzen in der Bevölkerung mit bis zu 85% eine hohe Prävalenz aufweisen. Die perkutane Radiofrequenz-Facettengelenkdenervation (PRFD) ist heute der Goldstandard bei der Rhizotomie von chronischen Kreuzschmerzen (CLBP). Bisher veröffentlichte Studien zeigen jedoch kontroverse Ergebnisse über die Wirksamkeit der PRFD. Ziel dieser Studie war es daher, den Einsatz der endoskopischen Facettengelenkdenervation (EJE) zur Behandlung chronischer Kreuzschmerzen zu analysieren und potenzielle Risikofaktoren zu ermitteln, die die Indikationen für den Eingriff einschränken könnten.Wir haben retrospektiv 31 Patienten in die Studie eingeschlossen, die seit mindestens 24 Monaten an chronische Kreuzschmerzen leiden. Alle Patienten wurden einer endoskopischen Facettengelenkdenervation unterzogen und mussten postoperativ ODI-, COMI-, EQ-5D- und VRS-Scores ausfüllen, wobei die Nachbeobachtungszeit mindestens 12 Monate betrug. Zur Analyse der Korrelationen wurden grundlegende Patientendaten erfasst.Bei allen gemessenen klinischen Werten, wie ODI, COMI, EQ-5D und VRS, wurde eine signifikante Verbesserung festgestellt. Während das beste Ergebnis bei der 3-monatigen Nachuntersuchung erzielt wurde, wurde bei der 12-monatigen Nachuntersuchung eine leichte Verschlechterung festgestellt. Im Vergleich zu den präoperativen Scores wurde jedoch ein signifikanter Nutzen festgestellt. 28/31 Patienten (93,3%) berichteten bei der Nachuntersuchung nach 12 Monaten über geringere Schmerzen und waren mit dem Verfahren zufrieden. Älteres Alter und psychiatrische Vorerkrankungen wurden als potenzielle Risikofaktoren identifiziert, die mit einem schlechteren Ergebnis einhergehen. Postoperative Komplikationen wie Hämatome, eine Sensibilitätsstörung und eine vorübergehende Muskelschwäche der unteren Extremitäten wurden selten beobachtet.Die endoskopische Facettengelenkdenervation zeigte eine signifikante Verbesserung der klinischen Ergebnisse und der VRS im Vergleich zu den präoperativen Werten von Patienten mit einer mindestens 12 Monate bestehenden chronischen Kreuzschmerzen vor der Operation. Ältere Patienten und Patienten mit psychiatrischen Vorerkrankungen profitieren weniger von dem Eingriff.}, } @article {pmid39187176, year = {2025}, author = {Althobaiti, NA}, title = {Heavy metals exposure and Alzheimer's disease: Underlying mechanisms and advancing therapeutic approaches.}, journal = {Behavioural brain research}, volume = {476}, number = {}, pages = {115212}, doi = {10.1016/j.bbr.2024.115212}, pmid = {39187176}, issn = {1872-7549}, mesh = {Humans ; *Alzheimer Disease/chemically induced ; *Metals, Heavy/adverse effects ; Animals ; Oxidative Stress/drug effects/physiology ; Environmental Exposure/adverse effects ; Brain/drug effects/metabolism ; }, abstract = {Heavy metals such as lead, cadmium, mercury, and arsenic are prevalent in the environment due to both natural and anthropogenic sources, leading to significant public health concerns. These heavy metals are known to cause damage to the nervous system, potentially leading to a range of neurological conditions including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), and attention-deficit hyperactivity disorder (ADHD). The present study examines the complex relationship between heavy metal exposure and AD, focusing on the underlying mechanisms of toxicity and potential therapeutic approaches. This review article highlights how these metals can impair brain function through mechanisms such as oxidative stress, inflammation, and neurotransmitter disruption, ultimately contributing to neurodegenerative diseases like AD. It also addresses the challenges in diagnosing heavy metal-induced cognitive impairments and emphasizes the need for further research to explore effective treatment strategies and preventive measures against heavy metal exposure.}, } @article {pmid39187026, year = {2024}, author = {Rezaei, K and Mastali, G and Abbasgholinejad, E and Bafrani, MA and Shahmohammadi, A and Sadri, Z and Zahed, MA}, title = {Cadmium neurotoxicity: Insights into behavioral effect and neurodegenerative diseases.}, journal = {Chemosphere}, volume = {364}, number = {}, pages = {143180}, doi = {10.1016/j.chemosphere.2024.143180}, pmid = {39187026}, issn = {1879-1298}, mesh = {*Cadmium/toxicity ; Humans ; *Neurodegenerative Diseases/chemically induced ; Animals ; Environmental Pollutants/toxicity ; Brain/drug effects/metabolism ; Neurotoxicity Syndromes/etiology ; Neurons/drug effects ; }, abstract = {Cadmium (Cd) induced neurotoxicity has become a growing concern due to its potential adverse effects on the Central Nervous System. Cd is a Heavy Metal (HM) that is released into the environment, through several industrial processes. It poses a risk to the health of the community by polluting air, water, and soil. Cd builds up in the brain and other neural tissues, raising concerns about its effect on the nervous system due to its prolonged biological half-life. Cd can enter into the neurons, hence increasing the production of Reactive Oxygen Species (ROS) in them and impairing their antioxidant defenses. Cd disrupts the Calcium (Ca[2+]) balance in neurons, affects the function of the mitochondria, and triggers cell death pathways. As a result of these pathways, the path to the development of many neurological diseases affected by environmental factors, especially Cd, such as Alzheimer's Disease (AD) and Amyotrophic Lateral Sclerosis (ALS) is facilitated. There are cognitive deficits associated with long exposure to Cd. Memory disorders are present in both animals and humans. Cd alters the brain's function and performance in critical periods. There are lifelong consequences of Cd exposure during critical brain development stages. The susceptibility to neurotoxic effects is increased by interactions with a variety of risk factors. Cd poses risks to neuronal function and behavior, potentially contributing to neurodegenerative diseases like Parkinson's disease (PD) and AD as well as cognitive issues. This article offers a comprehensive overview of Cd-induced neurotoxicity, encompassing risk assessment, adverse effect levels, and illuminating intricate pathways.}, } @article {pmid39185513, year = {2024}, author = {Benatar, M and Macklin, EA and Malaspina, A and Rogers, ML and Hornstein, E and Lombardi, V and Renfrey, D and Shepheard, S and Magen, I and Cohen, Y and Granit, V and Statland, JM and Heckmann, JM and Rademakers, R and McHutchison, CA and Petrucelli, L and McMillan, CT and Wuu, J}, title = {Prognostic Clinical and Biological Markers for Amyotrophic Lateral Sclerosis Disease Progression: Validation and Implications for Clinical Trial Design and Analysis.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, pmid = {39185513}, support = {U54 NS092091/NS/NINDS NIH HHS/United States ; U19 AG063911/AG/NIA NIH HHS/United States ; R01 AG066152/AG/NIA NIH HHS/United States ; U01 NS107027/NS/NINDS NIH HHS/United States ; P01 AG066597/AG/NIA NIH HHS/United States ; P01 NS084974/NS/NINDS NIH HHS/United States ; P30 AG062677/AG/NIA NIH HHS/United States ; R01 NS109260/NS/NINDS NIH HHS/United States ; U54 NS123743/NS/NINDS NIH HHS/United States ; P30 AG072979/AG/NIA NIH HHS/United States ; R35 NS097273/NS/NINDS NIH HHS/United States ; T32 AG076411/AG/NIA NIH HHS/United States ; }, abstract = {BACKGROUND: With increasing recognition of the value of incorporating prognostic markers into amyotrophic lateral sclerosis (ALS) trial design and analysis plans, there is a pressing need to understand which among the prevailing clinical and biochemical markers have real value, and how they can be optimally used.

METHODS: A subset of patients with ALS recruited through the multi-center Phenotype-Genotype-Biomarker study (clinicaltrials.gov: NCT02327845) was identified as "trial-like" based on meeting common trial eligibility criteria. Clinical phenotyping was performed by evaluators trained in relevant assessments. Serum neurofilament light (NfL) and phosphorylated neurofilament heavy (pNfH), urinary p75[ECD], plasma microRNA-181, and an array of biochemical and clinical measures were evaluated for their prognostic value. Associations with functional progression were estimated by random-slopes mixed models of ALS functional rating scale-revised (ALSFRS-R) score. Associations with survival were estimated by log-rank test and Cox proportional hazards regression. Potential sample size savings from adjusting for given biomarkers in a hypothetical trial were estimated.

FINDINGS: Baseline serum NfL is a powerful prognostic biomarker, predicting survival and ALSFRS-R rate of decline. Serum NfL <40pg/ml and >100pg/ml correspond to future ALSFRS-R slopes of ~0.5 and 1.5 points/month, respectively. Serum NfL also adds value to the best available clinical predictors, encapsulated by the European Network to Cure ALS (ENCALS) predictor score. In models of functional decline, the addition of NfL yields ~25% sample size saving above those achieved by inclusion of either clinical predictors or ENCALS score alone. The prognostic value of serum pNfH, urinary p75[ECD], and plasma miR-181ab is more limited.

INTERPRETATION: Among the multitude of biomarkers considered, only blood NfL adds value to the ENCALS prediction model and should be incorporated into analysis plans for all ongoing and future ALS trials. Defined thresholds of NfL might also be used in trial design, for enrichment or stratified randomisation, to improve trial efficiency.

FUNDING: NIH (U01-NS107027, U54-NS092091). ALSA (16-TACL-242).}, } @article {pmid39185360, year = {2024}, author = {Di Lazzaro, V and Ranieri, F and Doretti, A and Boscarino, M and Maderna, L and Colombo, E and Soranna, D and Zambon, A and Ticozzi, N and Musumeci, G and Capone, F and Silani, V}, title = {Transcranial static magnetic stimulation for amyotrophic lateral sclerosis: a bicentric, randomised, double-blind placebo-controlled phase 2 trial.}, journal = {The Lancet regional health. Europe}, volume = {45}, number = {}, pages = {101019}, pmid = {39185360}, issn = {2666-7762}, abstract = {BACKGROUND: Enhanced glutamatergic transmission leading to motor neuron death is considered the major pathophysiological mechanism of amyotrophic lateral sclerosis (ALS). Motor cortex excitability can be suppressed by transcranial static magnetic stimulation (tSMS), thus tSMS can be evaluated as a potential treatment for ALS. The aim of present study was to investigate the efficacy and safety of tSMS in ALS.

METHODS: In this phase 2 trial, we randomly assigned ALS patients to receive daily tSMS or placebo stimulation over a period of 6 months. For each participant we calculated mean disease monthly progression rate (MPR) as the variation of the total ALS Functional Rating Scale-Revised (ALSRFS-R) score, before the beginning of the treatment (over a period of at least three months) and over the six-month treatment period. The primary efficacy outcome was the difference in MPR before and after the beginning of treatment. Secondary outcomes included safety and tolerability, compliance, and changes in corticospinal output. A long-term follow-up of 18 months was performed in all patients who completed the six-month treatment considering a composite endpoint event (tracheostomy or death). Trial registered at ClinicalTrials.gov, ID: NCT04393467, status: closed.

FINDINGS: Forty participants were randomly assigned to real (n = 21) or placebo stimulation (n = 19). Thirty-two participants (18 real and 14 placebo) completed the 6-month treatment. The MPR did not show statistically significant differences between the two arms during the pre-treatment (mean ± Standard deviation; Real: 1.02 ± 0.62, Sham: 1.02 ± 0.57, p-value = 1.00) and treatment period (Real: 0.90 ± 0.55, Sham: 0.94 ± 0.55, p-value = 0.83). Results for secondary clinical endpoints showed that the treatment is feasible and safe, being compliance with tSMS high. The change in corticospinal output did not differ significantly between the two groups. At the end of the long-term follow-up of 18 months, patients of real group had a statistically significant higher tracheostomy-free survival compared with patients of placebo group (Hazard Ratio = 0.27 95% Confidence interval 0.09-0.80, p-value = 0.019).

INTERPRETATION: tSMS did not modify disease progression during the 6 months of treatment. However, long-term follow-up revealed a substantial increase in tracheostomy free survival in patients treated with real stimulation supporting the evaluation of tSMS in larger and more prolonged studies.

FUNDING: The "Fondazione 'Nicola Irti' per le opere di carità e di cultura", Rome, Italy, supported present study.}, } @article {pmid39184484, year = {2024}, author = {Ozceylan, O and Sezgin-Bayindir, Z}, title = {Current Overview on the Use of Nanosized Drug Delivery Systems in the Treatment of Neurodegenerative Diseases.}, journal = {ACS omega}, volume = {9}, number = {33}, pages = {35223-35242}, pmid = {39184484}, issn = {2470-1343}, abstract = {Neurodegenerative diseases, encompassing conditions such as Alzheimer's disease, Parkinson's disease, multiple sclerosis, amyotrophic lateral sclerosis, prion disease, and Huntington's disease, present a growing health concern as human life expectancy increases. Despite this, effective treatments to halt disease progression remain elusive due to various factors, including challenges in drug delivery across physiological barriers like the blood-brain barrier and patient compliance issues leading to treatment discontinuation. In response, innovative treatment approaches leveraging noninvasive techniques with higher patient compliance are emerging as promising alternatives. This Review aims to synthesize current treatment options and the challenges encountered in managing neurodegenerative diseases, while also exploring innovative treatment modalities. Specifically, noninvasive strategies such as intranasal administration and nanosized drug delivery systems are gaining prominence for their potential to enhance treatment efficacy and patient adherence. Nanosized drug delivery systems, including liposomes, polymeric micelles, and nanoparticles, are evaluated within the context of outstanding studies. The advantages and disadvantages of these approaches are discussed, providing insights into their therapeutic potential and limitations. Through this comprehensive examination, this Review contributes to the ongoing discourse surrounding the development of effective treatments for neurodegenerative diseases.}, } @article {pmid39183919, year = {2024}, author = {Ma, S and Cao, Y and Shi, YF and Shang, C and He, L and Liu, ZP}, title = {Data-driven discovery of active phosphine ligand space for cross-coupling reactions.}, journal = {Chemical science}, volume = {15}, number = {33}, pages = {13359-13368}, pmid = {39183919}, issn = {2041-6520}, abstract = {The design of highly active catalysts is a main theme in organic chemistry, but it still relies heavily on expert experience. Herein, powered by machine-learning global structure exploration, we forge a Metal-Phosphine Catalyst Database (MPCD) with a meticulously designed ligand replacement energy metric, a key descriptor to describe the metal-ligand interactions. It pushes the rational design of organometallic catalysts to a quantitative era, where a ±10 kJ mol[-1] window of relative ligand binding strength, a so-called active ligand space (ALS), is identified for highly effective catalyst screening. We highlight the chemistry interpretability and effectiveness of ALS for various C-N, C-C and C-S cross-coupling reactions via a Sabatier-principle-based volcano plot and demonstrate its predictive power in discovering low-cost ligands in catalyzing Suzuki cross-coupling involving aryl chloride. The advent of the MPCD provides a data-driven new route for speeding up organometallic catalysis and other applications.}, } @article {pmid39183185, year = {2024}, author = {Adiningrat, DP and Schlund, M and Skidmore, AK and Abdullah, H and Wang, T and Heurich, M}, title = {Mapping temperate old-growth forests in Central Europe using ALS and Sentinel-2A multispectral data.}, journal = {Environmental monitoring and assessment}, volume = {196}, number = {9}, pages = {841}, pmid = {39183185}, issn = {1573-2959}, support = {397.ID 834709, H2020-EU.1.1//European Research Council,European Union/ ; 397.ID 834709, H2020-EU.1.1//European Research Council,European Union/ ; 397.ID 834709, H2020-EU.1.1//European Research Council,European Union/ ; 397.ID 834709, H2020-EU.1.1//European Research Council,European Union/ ; 397.ID 834709, H2020-EU.1.1//European Research Council,European Union/ ; }, mesh = {*Forests ; *Environmental Monitoring/methods ; Europe ; *Remote Sensing Technology ; Conservation of Natural Resources/methods ; Biodiversity ; Satellite Imagery ; Climate Change ; Lasers ; }, abstract = {Old-growth forests are essential to preserve biodiversity and play an important role in sequestering carbon and mitigating climate change. However, their existence across Europe is vulnerable due to the scarcity of their distribution, logging, and environmental threats. Therefore, providing the current status of old-growth forests across Europe is essential to aiding informed conservation efforts and sustainable forest management. Remote sensing techniques have proven effective for mapping and monitoring forests over large areas. However, relying solely on remote sensing spectral or structural information cannot capture comprehensive horizontal and vertical structure complexity profiles associated with old-growth forest characteristics. To overcome this issue, we combined spectral information from Sentinel-2A multispectral imagery with 3D structural information from high-density point clouds of airborne laser scanning (ALS) imagery to map old-growth forests over an extended area. Four features from the ALS data and fifteen from Sentinel-2A comprising raw band (spectral reflectance), vegetation indices (VIs), and texture were selected to create three datasets used in the classification process using the random forest algorithm. The results demonstrated that combining ALS and Sentinel-2A features improved the classification performance and yielded the highest accuracy for old-growth class, with an F1-score of 92% and producer's and user's accuracies of 93% and 90%, respectively. The findings suggest that features from ALS and Sentinel-2A data sensitive to forest structure are essential for identifying old-growth forests. Integrating open-access satellite imageries, such as Sentinel-2A and ALS data, can benefit forest managers, stakeholders, and conservationists in monitoring old-growth forest preservation across a broader spatial extent.}, } @article {pmid39182937, year = {2024}, author = {Silva, ST and Costa, IM and Souza, AA and Pondofe, K and Melo, LP and Resqueti, VR and Valentim, R and Gonçalves, F and Ribeiro, TS}, title = {Physical therapy for the management of global function, fatigue and quality of life in amyotrophic lateral sclerosis: systematic review and meta-analyses.}, journal = {BMJ open}, volume = {14}, number = {8}, pages = {e076541}, pmid = {39182937}, issn = {2044-6055}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/complications/therapy ; *Quality of Life ; *Physical Therapy Modalities ; *Fatigue/therapy/etiology ; Randomized Controlled Trials as Topic ; }, abstract = {OBJECTIVES: To critically evaluate the effectiveness of physical therapy interventions in improving global function, quality of life and fatigue in individuals with amyotrophic lateral sclerosis (ALS).

DESIGN: Systematic review and meta-analyses.

DATA SOURCES: MEDLINE, EMBASE, Cochrane Library (CENTRAL) and Physiotherapy Evidence Database (PEDro) were searched through 31 January 2023.

ELIGIBILITY CRITERIA: We included randomised clinical trials (RCTs) that compared physical therapy interventions that act on global function, fatigue and quality of life in individuals with ALS with any other non-physiotherapeutic methods and techniques, placebo or non-intervention. The primary outcome measure was the evaluation of global function. Secondary outcomes were quality of life, fatigue and adverse events.

DATA EXTRACTION AND SYNTHESIS: Two independent authors used a researcher-developed extraction form and the Rayyan software to search, screen and code included studies. The risk of bias was assessed using the PEDro scale. Meta-analyses were conducted employing random effects. Outcomes were succinctly presented in Grading of Recommendations, Assessment, Development and Evaluation evidence profiles.

RESULTS: Our searches identified 39 415 references. After study selection, three studies were included in the review. Such studies involved 62 participants with a mean age of 54.6 years. In the evaluated trials, 40 were male, while 22 participants were female. Regarding the type of onset of the disease, 58 participants had spinal onset of ALS, and four had bulbar.

CONCLUSIONS: Physical therapy intervention may improve the global function of individuals with ALS in the short term; however, clinically, it was inconclusive. In terms of quality of life and fatigue, physical therapy intervention is not more effective than control in the short term. Adverse events are not increased by physical therapy intervention in the short term. Due to significant methodological flaws, small sample sizes, wide CIs and clinical interpretation, our confidence in the effect estimate is limited.

PROSPERO REGISTRATION NUMBER: CRD42021251350.}, } @article {pmid39182589, year = {2024}, author = {Pupillo, E and Bianchi, E and Bonetto, V and Pasetto, L and Bendotti, C and Paganoni, S and Mandrioli, J and Mazzini, L and , }, title = {Long-term survival of participants in a phase II randomized trial of RNS60 in amyotrophic lateral sclerosis.}, journal = {Brain, behavior, and immunity}, volume = {122}, number = {}, pages = {456-462}, doi = {10.1016/j.bbi.2024.08.044}, pmid = {39182589}, issn = {1090-2139}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/mortality/physiopathology ; Male ; Female ; Middle Aged ; Double-Blind Method ; Vital Capacity ; Aged ; *Disease Progression ; Biomarkers/blood ; Treatment Outcome ; Adult ; Neurofilament Proteins ; }, abstract = {BACKGROUND: Positive effects of RNS60 on respiratory and bulbar function were observed in a phase 2 randomized, placebo-controlled trial in people with amyotrophic lateral sclerosis (ALS).

OBJECTIVE: to investigate the long-term survival of trial participants and its association with respiratory status and biomarkers of neurodegeneration and inflammation.

STUDY DESIGN AND SETTINGS: A randomized, double blind, phase 2 clinical trial was conducted. Trial participants were enrolled at 22 Italian Expert ALS Centres from May 2017 to January 2020. Vital status of all participants was ascertained thirty-three months after the trial's last patient last visit (LPLV). Participants were patients with Amyotrophic Lateral Sclerosis, classified as slow or fast progressors based on forced vital capacity (FVC) slope during trial treatment. Demographic, clinical, and biomarker levels and their association with survival were also evaluated.

RESULTS: Mean duration of follow-up was 2.8 years. Long-term median survival was six months longer in the RNS60 group (p = 0.0519). Baseline FVC, and rates of FVC decline during the first 4 weeks of trial participation, were balanced between the active and placebo treatment arms. After 6 months of randomized, placebo-controlled treatment, FVC decline was significantly slower in the RNS60 group compared to the placebo group. Rates of FVC progression during the treatment were strongly associated with long-term survival (median survival: 3.7 years in slow FVC progressors; 1.6 years in fast FVC progressors). The effect of RNS60 in prolonging long-term survival was higher in participants with low neurofilament light chain (NfL) (median survival: >4 years in low NfL - RNS60 group; 3.3 years in low NfL - placebo group; 1.9 years in high NfL - RNS60 group; 1.8 years in high NfL - placebo group) and Monocyte Chemoattractant Protein-1 (MCP-1) (median survival: 3.7 years in low MCP-1 - RNS60 group; 2.3 years in low MCP-1 - placebo group; 2.8 years in high MCP-1 - RNS60 group; 2.6 years in high MCP-1 - placebo group) levels at baseline.

CONCLUSIONS AND RELEVANCE: In this post-hoc analysis, long term survival was longer in participants randomized to RNS60 compared with those randomized to placebo and was correlated with slower FVC progression rates, suggesting that longer survival may be mediated by the drug's effect on respiratory function. In these post-hoc analyses, the beneficial effect of RNS60 on survival was most pronounced in participants with low NfL and MCP-1 levels at study entry, suggesting that this could be a subgroup to target in future studies investigating the effects of RNS60 on survival.

TRIAL REGISTRATION: Study preregistered on 13/Jan/2017 in EUDRA-CT (2016-002382-62). The study was also registered at ClinicalTrials.gov number NCT03456882.}, } @article {pmid39182251, year = {2024}, author = {Peng, Y and Liu, G and Li, S and Li, Z and Song, J}, title = {A machine learning system for artificial ligaments with desired mechanical properties in ACL reconstruction applications.}, journal = {Journal of the mechanical behavior of biomedical materials}, volume = {159}, number = {}, pages = {106691}, doi = {10.1016/j.jmbbm.2024.106691}, pmid = {39182251}, issn = {1878-0180}, mesh = {*Machine Learning ; *Mechanical Phenomena ; *Anterior Cruciate Ligament Reconstruction/methods ; Materials Testing ; Humans ; Anterior Cruciate Ligament/surgery ; Neural Networks, Computer ; Biomechanical Phenomena ; Ligaments/surgery ; Artificial Organs ; Mechanical Tests ; }, abstract = {The anterior cruciate ligament is one of the important tissues to maintain the stability of the human knee joint, but it is difficult for this ligament to self-heal after injury. Consequently, transplantation of artificial ligaments (ALs) has gained widespread attention as an important alternative treatment method in recent years. However, accurately predicting the intricate mechanical properties of ALs remains a formidable challenge, particularly when employing theoretical frameworks such as braiding theory. This obstacle presents a significant impediment to achieving optimal AL design. Therefore, in this study, a high-precision machine learning model based on an artificial neural network was developed to rapidly and accurately predict the mechanical properties of ALs. The results showed that the proposed model achieved a reduction of 45.22% and 50.17% in the normalized root mean square error on the testing set when compared to traditional machine learning models (Random Forest and Support Vector Machine), demonstrating its higher accuracy. In addition, the design of ALs with desired mechanical properties was achieved by optimizing the braiding parameters, and its effectiveness was verified through experiments. The mechanical properties of the prepared ALs were able to fully meet the desired targets and were at least 2% higher. Finally, the influence weights of different braiding parameters on the mechanical properties of ALs were analyzed by feature importance.}, } @article {pmid39182178, year = {2024}, author = {Serizawa, S}, title = {Exploration of the Factors Impacting Sustained Clinical Care by Multidisciplinary Professionals for Amyotrophic Lateral Sclerosis.}, journal = {The Tokai journal of experimental and clinical medicine}, volume = {49}, number = {3}, pages = {110-116}, pmid = {39182178}, issn = {2185-2243}, mesh = {*Amyotrophic Lateral Sclerosis/therapy ; Humans ; Surveys and Questionnaires ; *Patient Care Team ; Japan ; Female ; Male ; Self-Assessment ; Motivation ; Health Personnel ; Middle Aged ; Adult ; Time Factors ; }, abstract = {OBJECTIVE: This study examined the experiences of multidisciplinary medical professionals in providing daily clinical care for patients with amyotrophic lateral sclerosis (ALS), with a focus placed on their persistence in sustaining clinical care for this patient group.

METHODS: A questionnaire survey was administered to multidisciplinary medical professionals involved in ALS care at three hospitals in western Kanagawa Prefecture, Japan. The questionnaire results were used to examine the relationships between years of medical experience, years of ALS care experience, self-evaluation, and motivation to continue providing clinical care to patients with ALS.

RESULTS: Of the 269 questionnaires distributed and 164 collected by the multidisciplinary medical professionals, 143 (53%) were deemed valid. Analysis revealed an association between "years of medical experience" with both "self-assessment of clinical care for ALS patients practice experience" and "commitment to continue clinical care for ALS patients," as well as between "years of ALS medical experience" and "self-assessment of clinical care for ALS patients."

CONCLUSION: Medical professionals with more than ten years of medical experience expressed their commitment to continue providing medical care in a comprehensive self-assessment of both the positive and negative aspects of their practice. Negative evaluations can be used to identify and improve ALS medical practices.}, } @article {pmid39182146, year = {2024}, author = {Kill, C and Manegold, RK and Fistera, D and Risse, J}, title = {Airway management and ventilation techniques in resuscitation during advanced life support: an update.}, journal = {Journal of anesthesia, analgesia and critical care}, volume = {4}, number = {1}, pages = {58}, pmid = {39182146}, issn = {2731-3786}, abstract = {For many years, ventilation has been an essential part of advanced life support (ALS) in cardiopulmonary resuscitation (CPR). Nevertheless, there is little evidence about the best method of ventilation during resuscitation for both out-of-hospital cardiac arrest (OHCA) and inhospital cardiac arrest (IHCA) patients. Effective ventilation is one of the two main keys to successful resuscitation. In this context, the question always arises as to which airway management, along with which ventilation mode, constitutes the best strategy. Conventional ventilation modes are not designed for cardiac arrest and show important limitations that must be considered when used in CPR. Manual ventilation without the use of an automated transport ventilator (ATV) could be shown to be uncontrolled in applied volumes and pressures and should be avoided. Mechanical ventilation with an ATV is therefore superior to manual ventilation, but both volume- and pressure-controlled ventilation modes are significantly influenced by chest compressions. With the newly designed chest compression synchronized ventilation (CCSV), a special ventilation mode for resuscitation is available. Further research should be conducted to obtain more evidence of the effect of ventilation during CPR on outcomes following OHCA and not only about how to secure the airway for ventilation during CPR.}, } @article {pmid39181624, year = {2024}, author = {Mousele, C and Holden, D and Gnanapavan, S}, title = {Neurofilaments in neurologic disease.}, journal = {Advances in clinical chemistry}, volume = {123}, number = {}, pages = {65-128}, doi = {10.1016/bs.acc.2024.06.010}, pmid = {39181624}, issn = {2162-9471}, mesh = {Humans ; *Nervous System Diseases/pathology/metabolism/diagnosis ; *Biomarkers ; Neurofilament Proteins/cerebrospinal fluid/metabolism ; Intermediate Filaments/metabolism ; Animals ; }, abstract = {Neurofilaments (NFs), major cytoskeletal constituents of neurons, have emerged as universal biomarkers of neuronal injury. Neuroaxonal damage underlies permanent disability in various neurological conditions. It is crucial to accurately quantify and longitudinally monitor this damage to evaluate disease progression, evaluate treatment effectiveness, contribute to novel treatment development, and offer prognostic insights. Neurofilaments show promise for this purpose, as their levels increase with neuroaxonal damage in both cerebrospinal fluid and blood, independent of specific causal pathways. New assays with high sensitivity allow reliable measurement of neurofilaments in body fluids and open avenues to investigate their role in neurological disorders. This book chapter will delve into the evolving landscape of neurofilaments, starting with their structure and cellular functions within neurons. It will then provide a comprehensive overview of their broad clinical value as biomarkers in diseases affecting the central or peripheral nervous system.}, } @article {pmid39181183, year = {2024}, author = {Ko, YH and Lokareddy, RK and Doll, SG and Yeggoni, DP and Girdhar, A and Mawn, I and Klim, JR and Rizvi, NF and Meyers, R and Gillilan, RE and Guo, L and Cingolani, G}, title = {Single Acetylation-mimetic Mutation in TDP-43 Nuclear Localization Signal Disrupts Importin α1/β Signaling.}, journal = {Journal of molecular biology}, volume = {436}, number = {20}, pages = {168751}, pmid = {39181183}, issn = {1089-8638}, support = {P30 GM124166/GM/NIGMS NIH HHS/United States ; RF1 NS121143/NS/NINDS NIH HHS/United States ; R21 NS128396/NS/NINDS NIH HHS/United States ; S10 OD017987/OD/NIH HHS/United States ; R01 NS121143/NS/NINDS NIH HHS/United States ; R35 GM140733/GM/NIGMS NIH HHS/United States ; S10 OD023479/OD/NIH HHS/United States ; R35 GM138109/GM/NIGMS NIH HHS/United States ; HHSN261200800001E/CA/NCI NIH HHS/United States ; }, mesh = {*Nuclear Localization Signals/metabolism/genetics ; Humans ; *DNA-Binding Proteins/metabolism/genetics ; *alpha Karyopherins/metabolism/genetics ; *beta Karyopherins/metabolism/genetics ; *Amyotrophic Lateral Sclerosis/metabolism/genetics/pathology ; Acetylation ; *Signal Transduction ; Mutation ; Protein Processing, Post-Translational ; Active Transport, Cell Nucleus ; Protein Binding ; Cell Nucleus/metabolism ; }, abstract = {Cytoplasmic aggregation of the TAR-DNA binding protein of 43 kDa (TDP-43) is the hallmark of sporadic amyotrophic lateral sclerosis (ALS). Most ALS patients with TDP-43 aggregates in neurons and glia do not have mutations in the TDP-43 gene but contain aberrantly post-translationally modified TDP-43. Here, we found that a single acetylation-mimetic mutation (K82Q) near the TDP-43 minor Nuclear Localization Signal (NLS) box, which mimics a post-translational modification identified in an ALS patient, can lead to TDP-43 mislocalization to the cytoplasm and irreversible aggregation. We demonstrate that the acetylation mimetic disrupts binding to importins, halting nuclear import and preventing importin α1/β anti-aggregation activity. We propose that perturbations near the NLS are an additional mechanism by which a cellular insult other than a genetically inherited mutation leads to TDP-43 aggregation and loss of function. Our findings are relevant to deciphering the molecular etiology of sporadic ALS.}, } @article {pmid39181135, year = {2024}, author = {Wu, R and Ye, Y and Dong, D and Zhang, Z and Wang, S and Li, Y and Wright, N and Redding-Ochoa, J and Chang, K and Xu, S and Tu, X and Zhu, C and Ostrow, LW and Roca, X and Troncoso, JC and Wu, B and Sun, S}, title = {Disruption of nuclear speckle integrity dysregulates RNA splicing in C9ORF72-FTD/ALS.}, journal = {Neuron}, volume = {112}, number = {20}, pages = {3434-3451.e11}, pmid = {39181135}, issn = {1097-4199}, support = {P30 AG066507/AG/NIA NIH HHS/United States ; R01 NS107347/NS/NINDS NIH HHS/United States ; RF1 NS113820/NS/NINDS NIH HHS/United States ; RF1 NS127925/NS/NINDS NIH HHS/United States ; R01 AG078948/AG/NIA NIH HHS/United States ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology ; *C9orf72 Protein/genetics/metabolism ; *Frontotemporal Dementia/genetics/metabolism/pathology ; Mice ; Animals ; *RNA Splicing/genetics ; *RNA-Binding Proteins/metabolism/genetics ; Induced Pluripotent Stem Cells/metabolism ; DNA Repeat Expansion/genetics ; Neurons/metabolism ; Male ; Female ; }, abstract = {Expansion of an intronic (GGGGCC)n repeat within the C9ORF72 gene is the most common genetic cause of both frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) (C9-FTD/ALS), characterized with aberrant repeat RNA foci and noncanonical translation-produced dipeptide repeat (DPR) protein inclusions. Here, we elucidate that the (GGGGCC)n repeat RNA co-localizes with nuclear speckles and alters their phase separation properties and granule dynamics. Moreover, the essential nuclear speckle scaffold protein SRRM2 is sequestered into the poly-GR cytoplasmic inclusions in the C9-FTD/ALS mouse model and patient postmortem tissues, exacerbating the nuclear speckle dysfunction. Impaired nuclear speckle integrity induces global exon skipping and intron retention in human iPSC-derived neurons and causes neuronal toxicity. Similar alternative splicing changes can be found in C9-FTD/ALS patient postmortem tissues. This work identified novel molecular mechanisms of global RNA splicing defects caused by impaired nuclear speckle function in C9-FTD/ALS and revealed novel potential biomarkers or therapeutic targets.}, } @article {pmid39180957, year = {2024}, author = {Harkins, AL and Ambegaokar, PP and Keeler, AM}, title = {Immune responses to central nervous system directed adeno-associated virus gene therapy: Does direct CNS delivery make a difference?.}, journal = {Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics}, volume = {21}, number = {4}, pages = {e00435}, pmid = {39180957}, issn = {1878-7479}, support = {P01 HL158506/HL/NHLBI NIH HHS/United States ; }, mesh = {Humans ; *Dependovirus/genetics/immunology ; *Genetic Therapy/methods ; *Genetic Vectors/immunology/administration & dosage ; Animals ; Central Nervous System/immunology ; Gene Transfer Techniques ; Central Nervous System Diseases/therapy/immunology ; }, abstract = {Adeno-associated virus (AAV) mediated gene therapy is a leading gene delivery platform with potential to transform the landscape of treatment for neurological disorders. While AAV is deemed non-immunogenic compared to other viral vectors, adverse immune reactions have been observed in the clinic, raising concerns. As the central nervous system (CNS) has a tightly regulated immune system, characterized by a degree of tolerance, it has been considered a unique target for AAV gene therapy. AAV vectors have shown promising results for the treatment of several CNS disorders including Spinal Muscular Atrophy, Giant Axonal Neuropathy, Amyotrophic Lateral Sclerosis, Tay Sachs Disease, Parkinson's Disease, and others, demonstrating safety and success. The Food and Drug Administration (FDA) approval of Zolgensma and European Medicines Agency (EMA) approval of Upstaza, for Spinal Muscular Atrophy (SMA) and Aromatic l-amino acid decarboxylase deficiency (AADC) respectively, represent this success, all while highlighting significant differences in immune responses to AAV, particularly with regards to therapeutic administration route. AAV therapies like Upstaza that are injected directly into the immune-specialized brain have been characterized by mild immune response profiles and minor adverse events, whereas therapies like Zolgensma that are injected systemically demonstrate more robust immune stimulation and off-target toxicities. Despite these contrasting parallels, these therapeutics and others in the clinic have demonstrated clinical benefit for patients, warranting further exploration of immune responses to CNS-directed AAV clinical trials. Thus, in this review, we discuss effects of different routes of AAV administration on eliciting local and peripheral immune responses specifically observed in CNS-targeted trials.}, } @article {pmid39180748, year = {2024}, author = {Liu, Z and Zhang, H and Lu, K and Chen, L and Zhang, Y and Xu, Z and Zhou, H and Sun, J and Xu, M and Ouyang, Q and Thompson, GJ and Yang, Y and Su, N and Cai, X and Cao, L and Zhao, Y and Jiang, L and Zheng, Y and Zhang, X}, title = {Low-intensity pulsed ultrasound modulates disease progression in the SOD1[G93A] mouse model of amyotrophic lateral sclerosis.}, journal = {Cell reports}, volume = {43}, number = {9}, pages = {114660}, doi = {10.1016/j.celrep.2024.114660}, pmid = {39180748}, issn = {2211-1247}, mesh = {Animals ; *Amyotrophic Lateral Sclerosis/genetics/pathology/therapy/metabolism ; *Disease Models, Animal ; Mice ; *Disease Progression ; *Ultrasonic Waves ; *Mice, Transgenic ; *Motor Cortex/pathology/metabolism ; TRPV Cation Channels/metabolism/genetics ; Superoxide Dismutase-1/genetics/metabolism ; Cerebrovascular Circulation ; Ultrasonic Therapy/methods ; Mice, Inbred C57BL ; Male ; Endothelial Cells/metabolism ; Motor Neurons/pathology/metabolism ; Humans ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by the progressive loss of motor neurons in the brain and spinal cord, and there are no effective drug treatments. Low-intensity pulsed ultrasound (LIPUS) has garnered attention as a promising noninvasive neuromodulation method. In this study, we investigate its effects on the motor cortex and underlying mechanisms using the SOD1[G93A] mouse model of ALS. Our results show that LIPUS treatment delays disease onset and prolongs lifespan in ALS mice. LIPUS significantly increases cerebral blood flow in the motor cortex by preserving vascular endothelial cell integrity and increasing microvascular density, which may be mediated via the ion channel TRPV4. RNA sequencing analysis reveals that LIPUS substantially reduces the expression of genes associated with neuroinflammation. These findings suggest that LIPUS applied to the motor cortex may represent a potentially effective therapeutic tool for the treatment of ALS.}, } @article {pmid39180568, year = {2024}, author = {Yang, J and Tang, C}, title = {Causal relationship between imaging-derived phenotypes and neurodegenerative diseases: a Mendelian randomization study.}, journal = {Mammalian genome : official journal of the International Mammalian Genome Society}, volume = {35}, number = {4}, pages = {711-723}, pmid = {39180568}, issn = {1432-1777}, mesh = {Humans ; *Mendelian Randomization Analysis ; *Neurodegenerative Diseases/genetics/diagnostic imaging ; *Phenotype ; *Amyotrophic Lateral Sclerosis/genetics/diagnostic imaging ; Alzheimer Disease/genetics/diagnostic imaging ; Frontotemporal Dementia/genetics/diagnostic imaging/pathology ; Parkinson Disease/genetics/diagnostic imaging ; Brain/diagnostic imaging/pathology/metabolism ; Multiple Sclerosis/genetics/diagnostic imaging ; Neuroimaging/methods ; }, abstract = {Neurodegenerative diseases are incurable conditions that lead to gradual and progressive deterioration of brain function in patients. With the aging population, the prevalence of these diseases is expected to increase, posing a significant economic burden on society. Imaging techniques play a crucial role in the diagnosis and monitoring of neurodegenerative diseases. This study utilized a two-sample Mendelian randomization (MR) analysis to assess the causal relationship between different imaging-derived phenotypes (IDP) in the brain and neurodegenerative diseases. Multiple MR methods were employed to minimize bias and obtain reliable estimates of the potential causal relationship between the variable exposures of interest and the outcomes. The study found potential causal relationships between different IDPs and Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), and frontotemporal dementia (FTD). Specifically, the study identified potential causal relationships between 2 different types of IDPs and AD, 8 different types of IDPs and PD, 11 different types of imaging-derived phenotypes and ALS, 1 type of IDP and MS, and 1 type of IDP and FTD. This study provides new insights for the prevention, diagnosis, and treatment of neurodegenerative diseases, offering important clues for understanding the pathogenesis of these diseases and developing relevant intervention strategies.}, } @article {pmid39180054, year = {2024}, author = {Spittel, S and Meyer, T and Weyen, U and Grehl, T and Weydt, P and Steinbach, R and Petri, S and Baum, P and Metelmann, M and Sperfeld, AD and Kettemann, D and Norden, J and Rödiger, A and Ilse, B and Grosskreutz, J and Hildebrandt, B and Walter, B and Münch, C and Maier, A}, title = {User expectations and experiences of an assistive robotic arm in amyotrophic lateral sclerosis: a multicenter observational study.}, journal = {Neurological research and practice}, volume = {6}, number = {1}, pages = {42}, pmid = {39180054}, issn = {2524-3489}, abstract = {OBJECTIVE: Robotic arms are innovative assistive devices for ALS patients with progressive motor deficits of arms and hands. The objective was to explore the patients´ expectations towards a robotic arm system and to assess the actual experiences after the provision of the device.

METHODS: A prospective observational study was conducted at 9 ALS centers in Germany. ALS-related functional deficits were assessed using the ALS-Functional Rating Scale-revised (ALSFRS-R). Motor deficit of the upper limbs was determined using a subscore of three arm-related items of the ALSFRS-R (items 4-6; range 0-12 points). User expectations before provision (expectation group, n = 85) and user experiences after provision (experience group, n = 14) with the device (JACO Assistive Robotic Device, Kinova, Boisbriand, QC, Canada) were assessed.

RESULTS: In the total cohort, mean ALSFRS-R subscore for arm function was 1.7 (SD: 2.0, 0-9) demonstrating a severe functional deficit of the upper limbs. In the expectation group (n = 85), the following use cases of the robotic arm have been prioritized: handling objects (89%), close-body movements (88%), pressing buttons (87%), serving drinks (86%), and opening cabinets and doors (85%). In the experience group (n = 14), handling objects (79%), serving drinks (79%), near-body movements (71%), pushing buttons (71%), serving food (64%), and opening doors (64%) were the most frequent used cases. Most patients used the device daily (71.4%, n = 10), and 28.6% (n = 4) several times a week. All patients of the experience group found the device helpful, felt safe while using the device, and were satisfied with its reliability. NPS of the assistive robotic arm revealed 64% "promoters" (strong recommendation), 29% "indifferents" (uncertain recommendation) and 7% "detractors" (no recommendation). Total NPS was + 57 demonstrating strong patient satisfaction.

CONCLUSIONS: Initiation of procurement with a robotic assistive arm was confined to patients with severe functional deficit of the upper limbs. User experience underlined the wide spectrum of use cases of assistive robotic arms in ALS. The positive user experience together with high satisfaction underscore that robotic arm systems serve as a valuable treatment option in ALS patients with severe motor deficits of the arms.}, } @article {pmid39179240, year = {2025}, author = {Sisti, HM and Beebe, A and Gabrielsson, E and Bishop, M}, title = {Postmovement Beta Rebound in Real and Imagined Movement.}, journal = {Motor control}, volume = {29}, number = {1}, pages = {53-68}, pmid = {39179240}, issn = {1087-1640}, support = {P20 GM103449/GM/NIGMS NIH HHS/United States ; }, mesh = {Humans ; *Imagination/physiology ; Male ; Female ; Adult ; *Beta Rhythm/physiology ; *Electroencephalography ; *Movement/physiology ; *Psychomotor Performance/physiology ; Young Adult ; Sensorimotor Cortex/physiology ; }, abstract = {Movement disorders, such as stroke and amyotrophic lateral sclerosis, result in loss of upper limb function and, hence, severe impairments of bimanual coordination. Although motor imagery is increasingly used to enhance neurorehabilitation, cognitive and neurophysiological parameters that inform effective strategies remain elusive. The aim of the present study is to elucidate the neural dynamics that underlie learning during real and imagined movement using both unimanual and bimanual coordination patterns. The post movement beta rebound (PMBR) has been implicated as a biomarker of motor control and therefore was the focus of this study. Healthy adults (n = 21) learned a visuomotor tracking task in a single session using either one or both hands while brainwaves were captured using electroencephalography. Postmovement beta rebound was evident in the sensorimotor cortex for both unimanual and bimanual conditions. Task-related power of the beta band demonstrated that actual unimanual movement requires greater contralateral activity compared with both actual bimanual movement and imagined movement of either condition. Notably, the PMBR was evident even in imagined movement, although to a lesser extent than real movement. Neurophysiological results support a functional role for beta band in movement. Results of these data may inform neurorehabilitation strategies for patients recovering from movement disorders of the upper limbs.}, } @article {pmid39178140, year = {2024}, author = {Briois, V and Itié, JP and Polian, A and King, A and Traore, AS and Marceau, E and Ersen, O and La Fontaine, C and Barthe, L and Beauvois, A and Roudenko, O and Belin, S}, title = {Hyperspectral full-field quick-EXAFS imaging at the ROCK beamline for monitoring micrometre-sized heterogeneity of functional materials under process conditions.}, journal = {Journal of synchrotron radiation}, volume = {31}, number = {Pt 5}, pages = {1084-1104}, pmid = {39178140}, issn = {1600-5775}, support = {ANR-10-EQPX-0045//Agence Nationale de la Recherche/ ; ANR-20-CE42-007//Agence Nationale de la Recherche/ ; ANR-07-Stock-E-0 PULSSE//Agence Nationale de la Recherche/ ; }, abstract = {Full-field transmission X-ray microscopy has been recently implemented at the hard X-ray ROCK-SOLEIL quick-EXAFS beamline, adding micrometre spatial resolution to the second time resolution characterizing the beamline. Benefiting from a beam size versatility due to the beamline focusing optics, full-field hyperspectral XANES imaging has been successfully used at the Fe K-edge for monitoring the pressure-induced spin transition of a 150 µm × 150 µm Fe(o-phen)2(NCS)2 single crystal and the charge of millimetre-sized LiFePO4 battery electrodes. Hyperspectral imaging over 2000 eV has been reported for the simultaneous monitoring of Fe and Cu speciation changes during activation of a FeCu bimetallic catalyst along a millimetre-sized catalyst bed. Strategies of data acquisition and post-data analysis using Jupyter notebooks and multivariate data analysis are presented, and the gain obtained using full-field hyperspectral quick-EXAFS imaging for studies of functional materials under process conditions in comparison with macroscopic information obtained by non-spatially resolved quick-EXAFS techniques is discussed.}, } @article {pmid39177232, year = {2024}, author = {Witzel, S and Huss, A and Nagel, G and Rosenbohm, A and Rothenbacher, D and Peter, RS and Bäzner, H and Börtlein, A and Dempewolf, S and Schabet, M and Hecht, M and Kohler, A and Opherk, C and Naegele, A and Sommer, N and Lindner, A and Alexudis, C and Bachhuber, F and Halbgebauer, S and Brenner, D and Ruf, W and Weiland, U and Mayer, B and Schuster, J and Dorst, J and Tumani, H and Ludolph, AC and , }, title = {Population-Based Evidence for the Use of Serum Neurofilaments as Individual Diagnostic and Prognostic Biomarkers in Amyotrophic Lateral Sclerosis.}, journal = {Annals of neurology}, volume = {96}, number = {6}, pages = {1040-1057}, doi = {10.1002/ana.27054}, pmid = {39177232}, issn = {1531-8249}, support = {577631//Deutsche Forschungsgemeinschaft/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/blood/diagnosis ; *Biomarkers/blood ; *Neurofilament Proteins/blood ; Middle Aged ; Female ; Male ; Aged ; Prognosis ; Intermediate Filaments/metabolism ; Adult ; }, abstract = {OBJECTIVE: Neurofilament light chains (NfL) and phosphorylated neurofilament heavy chains (pNfH), established as diagnostic and prognostic biomarkers in hospital-based amyotrophic lateral sclerosis (ALS) cohorts, are now surrogate markers in clinical trials. This study extends their evaluation to a population level, with the aim of advancing their full establishment and assessing the transferability of biomarker findings from controlled cohorts to real-world ALS populations.

METHODS: We measured serum NfL and pNfH levels in all ALS patients (n = 790) and general population controls (n = 570) with available baseline samples participating in the epidemiological ALS Registry Swabia, providing platform-specific (ELLA™) reference data and Z-scores for controls, as well as reference data, disease-specific Z-scores and longitudinal data in ALS. We evaluated the diagnostic and prognostic utility of neurofilaments and quantified the impact of ALS-related factors and non-ALS confounders.

RESULTS: Neurofilaments showed high diagnostic and prognostic utility at the population level, with NfL superior to pNfH. The novel concept of a population-based ALS Z-score significantly improved the prognostic utility compared to absolute raw values. Both biomarkers increased more strongly with age in controls than in ALS, and age adjustment improved diagnostic accuracy. Our data show that disease progression rates, ALS phenotype, body mass index (BMI), and renal function need to be considered when interpreting neurofilament levels; longitudinal neurofilament levels were generally stable in individual patients, especially when adjusted for age and baseline levels.

INTERPRETATION: Population-based assessment enhances the utility of particularly serum NfL as a diagnostic and prognostic biomarker in ALS and improves the translation of findings from controlled cohorts to real-world populations. ANN NEUROL 2024;96:1040-1057.}, } @article {pmid39177131, year = {2024}, author = {Sheremeta, CL and Yarlagadda, S and Smythe, ML and Noakes, PG}, title = {Prostaglandins in the Inflamed Central Nervous System: Potential Therapeutic Targets.}, journal = {Current drug targets}, volume = {25}, number = {13}, pages = {885-908}, pmid = {39177131}, issn = {1873-5592}, support = {Project grant,//Muscular Dystrophy Association/ ; }, mesh = {Humans ; *Prostaglandins/metabolism ; Animals ; *Central Nervous System/metabolism/drug effects ; Alzheimer Disease/drug therapy/metabolism ; Signal Transduction/drug effects ; Multiple Sclerosis/drug therapy/metabolism ; Inflammation/drug therapy/metabolism ; Amyotrophic Lateral Sclerosis/drug therapy/metabolism ; Central Nervous System Diseases/drug therapy/metabolism ; }, abstract = {The global burden of neurological disorders is evident, yet there remains limited efficacious therapeutics for their treatment. There is a growing recognition of the role of inflammation in diseases of the central nervous system (CNS); among the numerous inflammatory mediators involved, prostaglandins play a crucial role. Prostaglandins are small lipid mediators derived from arachidonic acid via multi-enzymatic pathways. The actions of prostaglandins are varied, with each prostaglandin having a specific role in maintaining homeostasis. In the CNS, prostaglandins can have neuroprotective or neurotoxic properties depending on their specific G-protein receptor. These G-protein receptors have varying subfamilies, tissue distribution, and signal transduction cascades. Further studies into the impact of prostaglandins in CNS-based diseases may contribute to the clarification of their actions, hopefully leading to the development of efficacious therapeutic strategies. This review focuses on the roles played by prostaglandins in neural degeneration, with a focus on Alzheimer's Disease, Multiple Sclerosis, and Amyotrophic Lateral Sclerosis in both preclinical and clinical settings. We further discuss current prostaglandin-related agonists and antagonists concerning suggestions for their use as future therapeutics.}, } @article {pmid39176909, year = {2024}, author = {Tiffet, T and Pikaar, A and Trombert-Paviot, B and Jaulent, MC and Bousquet, C}, title = {Comparing a Large Language Model with Previous Deep Learning Models on Named Entity Recognition of Adverse Drug Events.}, journal = {Studies in health technology and informatics}, volume = {316}, number = {}, pages = {781-785}, doi = {10.3233/SHTI240528}, pmid = {39176909}, issn = {1879-8365}, mesh = {*Deep Learning ; *Drug-Related Side Effects and Adverse Reactions ; Humans ; Natural Language Processing ; Adverse Drug Reaction Reporting Systems ; }, abstract = {The ability to fine-tune pre-trained deep learning models to learn how to process a downstream task using a large training set allow to significantly improve performances of named entity recognition. Large language models are recent models based on the Transformers architecture that may be conditioned on a new task with in-context learning, by providing a series of instructions or prompt. These models only require few examples and such approach is defined as few shot learning. Our objective was to compare performances of named entity recognition of adverse drug events between state of the art deep learning models fine-tuned on Pubmed abstracts and a large language model using few-shot learning. Hussain et al's state of the art model (PMID: 34422092) significantly outperformed the ChatGPT-3.5 model (F1-Score: 97.6% vs 86.0%). Few-shot learning is a convenient way to perform named entity recognition when training examples are rare, but performances are still inferior to those of a deep learning model fine-tuned with several training examples. Perspectives are to evaluate few-shot prompting with GPT-4 and perform fine-tuning on GPT-3.5.}, } @article {pmid39176644, year = {2024}, author = {Turner, J and Impey, S and Gibbons, F and Bolger, A and Stephens, G and Hederman, L and Hamed, R and O'Meara, C and de la Varga, F and Kommala, J and Nicholson, M and Farrell, D and Galvin, M and Heverin, M and Mac Domhnaill, É and McFarlane, R and Meldrum, D and Murray, D and Hardiman, O}, title = {Data and Process Harmonisation of Multi-National, Multi-Site Research Data.}, journal = {Studies in health technology and informatics}, volume = {316}, number = {}, pages = {1411-1412}, doi = {10.3233/SHTI240675}, pmid = {39176644}, issn = {1879-8365}, mesh = {Humans ; *Data Collection ; Amyotrophic Lateral Sclerosis/therapy ; Biomedical Research ; }, abstract = {To achieve a single fully harmonised research data set suitable for analysis from data collected at multiple sites requires not only semantic integration of collection concepts and convergence onto single collection units, but harmonisation of data collection processes. We describe our experience of identifying harmonisation challenges in the Precision ALS project, with particular focus on process alignment challenges in a multi-site multi-national research data collection project.}, } @article {pmid39176177, year = {2024}, author = {Al Dera, H and AlQahtani, B}, title = {Molecular mechanisms and antisense oligonucleotide therapies of familial amyotrophic lateral sclerosis.}, journal = {Molecular therapy. Nucleic acids}, volume = {35}, number = {3}, pages = {102271}, pmid = {39176177}, issn = {2162-2531}, abstract = {Amyotrophic lateral sclerosis (ALS), a progressive neurodegenerative disease, presents considerable challenges in both diagnosis and treatment. It is categorized into sporadic and familial amyotrophic lateral sclerosis (fALS); the latter accounts for approximately 10% of cases and is primarily inherited in an autosomal dominant manner. This review summarizes the molecular genetics of fALS, highlighting key mutations that contribute to its pathogenesis, such as mutations in SOD1, FUS, and C9orf72. Central to this discourse is exploring antisense oligonucleotides (ASOs) that target these genetic aberrations, providing a promising therapeutic strategy. This review provides a detailed overview of the molecular mechanisms underlying fALS and the potential therapeutic value of ASOs, offering new insights into treating neurodegenerative diseases.}, } @article {pmid39175128, year = {2024}, author = {Wu, A and Lee, D and Xiong, WC}, title = {VPS35 or retromer as a potential target for neurodegenerative disorders: barriers to progress.}, journal = {Expert opinion on therapeutic targets}, volume = {28}, number = {8}, pages = {701-712}, pmid = {39175128}, issn = {1744-7631}, support = {R01 AG045781/AG/NIA NIH HHS/United States ; RF1 AG045781/AG/NIA NIH HHS/United States ; }, mesh = {Humans ; *Neurodegenerative Diseases/physiopathology/drug therapy ; *Vesicular Transport Proteins/metabolism ; Animals ; *Molecular Targeted Therapy ; Protein Transport ; Parkinson Disease/physiopathology/drug therapy ; Mutation, Missense ; Drug Development ; }, abstract = {INTRODUCTION: Vacuolar Protein Sorting 35 (VPS35) is pivotal in the retromer complex, governing transmembrane protein trafficking within cells, and its dysfunction is implicated in neurodegenerative diseases. A missense mutation, Asp620Asn (D620N), specifically ties to familial late-onset Parkinson's, while reduced VPS35 levels are observed in Alzheimer's, amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and tauopathies. VPS35's absence in certain neurons during development can initiate neurodegeneration, highlighting its necessity for neural health. Present therapeutic research mainly targets the clearance of harmful protein aggregates and symptom management. Innovative treatments focusing on VPS35 are under investigation, although fully understanding the mechanisms and optimal targeting strategies remain a challenge.

AREAS COVERED: This review offers a detailed account of VPS35's discovery, its role in neurodegenerative mechanisms - especially in Parkinson's and Alzheimer's - and its link to other disorders. It shines alight on recent insights into VPS35's function in development, disease, and as a therapeutic target.

EXPERT OPINION: VPS35 is integral to cellular function and disease association, making it a significant candidate for developing therapies. Progress in modulating VPS35's activity may lead to breakthrough treatments that not only slow disease progression but may also act as biomarkers for neurodegeneration risk, marking a step forward in managing these complex conditions.}, } @article {pmid39174972, year = {2024}, author = {Zhou, J and Li, F and Jia, B and Wu, Z and Huang, Z and He, M and Weng, H and So, KF and Qu, W and Fu, QL and Zhou, L}, title = {Intranasal delivery of small extracellular vesicles reduces the progress of amyotrophic lateral sclerosis and the overactivation of complement-coagulation cascade and NF-ĸB signaling in SOD1[G93A] mice.}, journal = {Journal of nanobiotechnology}, volume = {22}, number = {1}, pages = {503}, pmid = {39174972}, issn = {1477-3155}, support = {202310183302//2023 University Innovation and Entrepreneurship Training Plan/ ; 2022YFA1104900//National Key Research and Development Program of China/ ; 2021B1515120062//Basic and Applied Basic Research Foundation of Guangdong Province/ ; 2023B03J1233, 20220600003//Guangzhou Key R&D Program/ ; }, mesh = {Animals ; Male ; Mice ; Administration, Intranasal ; *Amyotrophic Lateral Sclerosis/metabolism ; Blood Coagulation ; Disease Models, Animal ; *Extracellular Vesicles/metabolism ; Mesenchymal Stem Cells/metabolism ; Mice, Inbred C57BL ; Mice, Transgenic ; Motor Neurons/metabolism ; *NF-kappa B/metabolism ; *Signal Transduction ; Spinal Cord/metabolism/pathology ; Superoxide Dismutase-1/genetics/metabolism ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal disease characterized by progressive motoneuron degeneration, and effective clinical treatments are lacking. In this study, we evaluated whether intranasal delivery of mesenchymal stem cell-derived small extracellular vesicles (sEVs) is a strategy for ALS therapy using SOD1[G93A] mice. In vivo tracing showed that intranasally-delivered sEVs entered the central nervous system and were extensively taken up by spinal neurons and some microglia. SOD1[G93A] mice that intranasally received sEV administration showed significant improvements in motor performances and survival time. After sEV administration, pathological changes, including spinal motoneuron death and synaptic denervation, axon demyelination, neuromuscular junction degeneration and electrophysiological defects, and mitochondrial vacuolization were remarkably alleviated. sEV administration attenuated the elevation of proinflammatory cytokines and glial responses. Proteomics and transcriptomics analysis revealed upregulation of the complement and coagulation cascade and NF-ĸB signaling pathway in SOD1[G93A] mouse spinal cords, which was significantly inhibited by sEV administration. The changes were further confirmed by detecting C1q and NF-ĸB expression using Western blots. In conclusion, intranasal administration of sEVs effectively delays the progression of ALS by inhibiting neuroinflammation and overactivation of the complement and coagulation cascades and NF-ĸB signaling pathway and is a potential option for ALS therapy.}, } @article {pmid39174694, year = {2024}, author = {Layalle, S and Aimond, F and Brugioti, V and Guissart, C and Raoul, C and Soustelle, L}, title = {The ALS-associated KIF5A P986L variant is not pathogenic for Drosophila motoneurons.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {19540}, pmid = {39174694}, issn = {2045-2322}, mesh = {Animals ; *Kinesins/genetics/metabolism ; *Motor Neurons/metabolism/pathology ; *Amyotrophic Lateral Sclerosis/genetics/pathology/metabolism ; Mutation ; Humans ; Drosophila Proteins/genetics/metabolism ; Drosophila ; Neuromuscular Junction/metabolism/pathology ; Drosophila melanogaster/genetics ; Synaptic Transmission/genetics ; Disease Models, Animal ; Axons/metabolism/pathology ; Larva/genetics/metabolism ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a devastating paralytic disorder caused by the death of motoneurons. Several mutations in the KIF5A gene have been identified in patients with ALS. Some mutations affect the splicing sites of exon 27 leading to its deletion (Δ27 mutation). KIF5A Δ27 is aggregation-prone and pathogenic for motoneurons due to a toxic gain of function. Another mutation found to be enriched in ALS patients is a proline/leucine substitution at position 986 (P986L mutation). Bioinformatic analyses strongly suggest that this variant is benign. Our study aims to conduct functional studies in Drosophila to classify the KIF5A P986L variant. When expressed in motoneurons, KIF5A P986L does not modify the morphology of larval NMJ or the synaptic transmission. In addition, KIF5A P986L is uniformly distributed in axons and does not disturb mitochondria distribution. Locomotion at larval and adult stages is not affected by KIF5A P986L. Finally, both KIF5A WT and P986L expression in adult motoneurons extend median lifespan compared to control flies. Altogether, our data show that the KIF5A P986L variant is not pathogenic for motoneurons and may represent a hypomorphic allele, although it is not causative for ALS.}, } @article {pmid39174305, year = {2025}, author = {Mohamed Yusoff, AA and Mohd Khair, SZN}, title = {Unraveling mitochondrial dysfunction: comprehensive perspectives on its impact on neurodegenerative diseases.}, journal = {Reviews in the neurosciences}, volume = {36}, number = {1}, pages = {53-90}, pmid = {39174305}, issn = {2191-0200}, mesh = {Humans ; *Neurodegenerative Diseases/metabolism ; *Mitochondria/metabolism ; Animals ; Mitochondrial Dynamics/physiology ; Mitochondrial Diseases/metabolism ; Mitophagy/physiology ; }, abstract = {Neurodegenerative diseases represent a significant challenge to modern medicine, with their complex etiology and progressive nature posing hurdles to effective treatment strategies. Among the various contributing factors, mitochondrial dysfunction has emerged as a pivotal player in the pathogenesis of several neurodegenerative disorders. This review paper provides a comprehensive overview of how mitochondrial impairment contributes to the development of neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis, driven by bioenergetic defects, biogenesis impairment, alterations in mitochondrial dynamics (such as fusion or fission), disruptions in calcium buffering, lipid metabolism dysregulation and mitophagy dysfunction. It also covers current therapeutic interventions targeting mitochondrial dysfunction in these diseases.}, } @article {pmid39174072, year = {2024}, author = {Yoon, R and Wong, JP and Chung-Lee, L and Akbarian, A and Abdulai, AF and Hou, R and Ho, M and Zinaic, R and Anoushka, A}, title = {Scoping review protocol: what is the state of evidence for the use of communication apps with immigrant seniors in long-term care and community settings?.}, journal = {BMJ open}, volume = {14}, number = {8}, pages = {e089939}, pmid = {39174072}, issn = {2044-6055}, mesh = {Humans ; *Emigrants and Immigrants ; *Long-Term Care ; *Mobile Applications ; Aged ; Research Design ; Communication Barriers ; Scoping Reviews As Topic ; }, abstract = {INTRODUCTION: First language care is critical for older immigrant adults with limited English proficiency, especially in long-term care settings where most residents require staff assistance and experience complex chronic conditions, resulting in multiple communication interactions where language poses a barrier. Although there are a myriad of cultural-language translation apps and devices available, there is a gap in both research and practice on the acceptability and feasibility of these digital resources within the context of long-term care and community settings for older immigrant adults, from a cultural relevance and digital health equity perspective. Our paper outlines a scoping review protocol to examine the state of the literature on the extent to which cultural-language translation apps are used in long-term care settings and community-based elder care. We will also examine the extent to which such apps bridge or further gaps in equitable, accessible and acceptable care for older immigrant adults with limited English language proficiency.

METHODS AND ANALYSIS: This scoping review protocol will employ an adapted five-stage framework outlined by Arksey and O'Malley guided by enhancements recommended by Levac et al and Colquhoun et al. Using the Joanna Briggs Institute's population, concept and context framework, we defined the scope of the scoping review by identifying the target population, concepts for investigation and the context within which the research is situated. We will conduct a search of the literature from 2005 to 2024 using five bibliographic databases from health sciences (Healthstar OVID, MEDLINE OVID and Cumulative Index to Nursing and Allied Health Literature (CINAHL) EBSCO), engineering (Engineering Village Elsevier) and a cross-disciplinary database (Web of Science Clarivate). The research team will adopt a critical, equity-focused approach for the scoping review by integrating Richardson et al's framework for Digital Health Equity into our analysis of the findings. This will ensure that health and social equity perspectives are integrated within our methodology and analytical lens. Our analysis will specifically examine selected studies for their engagement with health equity and their ability to address issues such as ageism, ableism and the digital divide within geriatric care.

ETHICS AND DISSEMINATION: Ethics approval is not required for this scoping review as it involves secondary analysis of published works and no primary data collection involving human subjects. Findings of the review will be shared with community partners and disseminated through publications, conferences and peer-reviewed publications.}, } @article {pmid39174002, year = {2024}, author = {Javaudin, F and Papin, M and Le Bastard, Q and Thibault, M and Boishardy, T and Brau, F and Laribi, S and Petrovic, T and Peluchon, T and Markarian, T and Volteau, C and Arnaudet, I and Pes, P and Le Conte, P}, title = {Early point-of-care echocardiography as a predictive factor for absence of return of spontaneous circulatory in out-of-hospital cardiac arrests: A multicentre observational study.}, journal = {Resuscitation}, volume = {203}, number = {}, pages = {110373}, doi = {10.1016/j.resuscitation.2024.110373}, pmid = {39174002}, issn = {1873-1570}, mesh = {Humans ; Male ; Female ; *Out-of-Hospital Cardiac Arrest/therapy ; Aged ; Prospective Studies ; Middle Aged ; *Echocardiography/methods ; *Cardiopulmonary Resuscitation/methods ; *Return of Spontaneous Circulation ; *Predictive Value of Tests ; Point-of-Care Systems ; Prognosis ; }, abstract = {INTRODUCTION: Early assessment of the prognosis of a patient in cardiac arrest during cardiopulmonary resuscitation is highly challenging. This study aims to evaluate the predictive outcome value of early point-of-care ultrasound (POCUS) in out-of-hospital settings.

METHODS: This observational, prospective, multicentre study's primary endpoint was the positive predictive value (PPV) of POCUS cardiac standstill within the first 12 min of advanced life support (ALS) initiation in determining the absence of return of spontaneous circulation (ROSC). A multivariate logistic regression model was constructed with adjustments for known predictive variables typically used in termination of resuscitation (TOR) rules.

RESULTS: A total of 293 patients were analysed, with a mean age of 66.6 ± 14.6 years, and a majority were men (75.8%). POCUS was performed on average 7.9 ± 2.6 min after ALS initiation. Among patients with cardiac standstill (72.4%), 16.0% achieved ROSC compared with 48.2% in those with visible cardiac motions. The PPV of early POCUS cardiac standstill for the absence of ROSC was 84.0%, 95% CI [78.3-88.6]. In multivariable analysis, only POCUS cardiac standstill (adjusted odds ratio [aOR] 3.89, 95% CI [1.86-8.17]) and end-tidal CO2 (ETCO2) value ≤37 mmHg (aOR 4.27, 95% CI [2.21-8.25]) were associated with the absence of ROSC.

CONCLUSION: Early POCUS cardiac standstill during CPR for out-of-hospital cardiac arrest was a reliable predictor of the absence of ROSC. However, its presence alone was not sufficient to determine the termination of resuscitation efforts.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03494153. Registered March 29, 2018.}, } @article {pmid39173710, year = {2025}, author = {Weber, MP and Strobel, RJ and Norman, AV and Kareddy, A and Young, A and Young, S and El Moheb, M and Noona, SWW and Wisniewski, AM and Quader, M and Mazzeffi, M and Yarboro, LT and Teman, NR}, title = {Cardiac Surgical Unit-Advanced Life Support-certified centers are associated with improved failure to rescue after cardiac arrest: A propensity score-matched analysis.}, journal = {The Journal of thoracic and cardiovascular surgery}, volume = {169}, number = {4}, pages = {1271-1281}, doi = {10.1016/j.jtcvs.2024.08.014}, pmid = {39173710}, issn = {1097-685X}, mesh = {Humans ; Male ; *Heart Arrest/therapy/mortality ; Female ; Propensity Score ; Middle Aged ; Aged ; *Advanced Cardiac Life Support/standards/education ; *Certification ; *Cardiac Surgical Procedures/adverse effects ; *Failure to Rescue, Health Care/statistics & numerical data ; Retrospective Studies ; }, abstract = {OBJECTIVE: The impact of Cardiac Surgical Unit-Advanced Life Support (CSU-ALS) training on failure to rescue after cardiac arrest (FTR-CA) is unknown. We hypothesized that institutional CSU-ALS certification would be associated with lower FTR-CA.

METHODS: Patients undergoing Society of Thoracic Surgeons index operations from 2020 to 2023 from a regional collaborative were analyzed. Each institution was surveyed regarding its status as a CSU-ALS-certified center. Patients stratified by CSU-ALS certification were 1:1 propensity score matched with subsequent multivariable model reviewing associations with FTR-CA.

RESULTS: A total of 12,209 patients were included in the study period across 15 institutions. Eight centers reported CSU-ALS certification. After propensity score matching, 2 patient cohorts were formed (n = 3557). Patients at CSU-ALS centers had greater rates of intensive care unit readmission (3.9% vs 2.3%, P < .01) and total operating room time (340 minutes vs 323 minutes, P < .01). Hospital readmission was less likely in the CSU-ALS centers (9.0% vs 10.1%, P < .01). There was no difference in the rate of postoperative cardiac arrest (1.8% vs 2.2%, P = .24) or operative mortality (2.5% vs 2.9%, P = .30). After risk adjustment, CSU-ALS centers (odds ratio, 0.30; 95% confidence interval, 0.12-0.72, P < .01) and greater-volume centers (odds ratio, 0.15; confidence interval, 0.03-0.74, P = .02) had reduced odds of FTR-CA.

CONCLUSIONS: Centers with CSU-ALS certification are associated with a lower risk-adjusted likelihood of FTR-CA. This highlights the importance of well-trained staff and treatment algorithms in the care of patients postcardiac surgery.}, } @article {pmid39172789, year = {2024}, author = {Ahmed, R and Liang, M and Hudson, RP and Rangadurai, AK and Huang, SK and Forman-Kay, JD and Kay, LE}, title = {Atomic resolution map of the solvent interactions driving SOD1 unfolding in CAPRIN1 condensates.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {121}, number = {35}, pages = {e2408554121}, pmid = {39172789}, issn = {1091-6490}, support = {FND-503573//Canadian Government | Canadian Institutes of Health Research (CIHR)/ ; 2015-04347//Canadian Government | Natural Sciences and Engineering Research Council of Canada (NSERC)/ ; FDN-148375//Canadian Government | Canadian Institutes of Health Research (CIHR)/ ; PJT-190060//Canadian Government | Canadian Institutes of Health Research (CIHR)/ ; }, mesh = {*Superoxide Dismutase-1/chemistry/metabolism/genetics ; Humans ; *Solvents/chemistry ; Protein Unfolding ; Protein Binding ; Protein Folding ; Models, Molecular ; Stress Granules/metabolism/chemistry ; RNA-Binding Proteins/metabolism/chemistry ; Protein Conformation ; Magnetic Resonance Spectroscopy ; }, abstract = {Biomolecules can be sequestered into membrane-less compartments, referred to as biomolecular condensates. Experimental and computational methods have helped define the physical-chemical properties of condensates. Less is known about how the high macromolecule concentrations in condensed phases contribute "solvent" interactions that can remodel the free-energy landscape of other condensate-resident proteins, altering thermally accessible conformations and, in turn, modulating function. Here, we use solution NMR spectroscopy to obtain atomic resolution insights into the interactions between the immature form of superoxide dismutase 1 (SOD1), which can mislocalize and aggregate in stress granules, and the RNA-binding protein CAPRIN1, a component of stress granules. NMR studies of CAPRIN1:SOD1 interactions, focused on both unfolded and folded SOD1 states in mixed phase and demixed CAPRIN1-based condensates, establish that CAPRIN1 shifts the SOD1 folding equilibrium toward the unfolded state through preferential interactions with the unfolded ensemble, with little change to the structure of the folded conformation. Key contacts between CAPRIN1 and the H80-H120 region of unfolded SOD1 are identified, as well as SOD1 interaction sites near both the arginine-rich and aromatic-rich regions of CAPRIN1. Unfolding of immature SOD1 in the CAPRIN1 condensed phase is shown to be coupled to aggregation, while a more stable zinc-bound, dimeric form of SOD1 is less susceptible to unfolding when solvated by CAPRIN1. Our work underscores the impact of the condensate solvent environment on the conformational states of resident proteins and supports the hypothesis that ALS mutations that decrease metal binding or dimerization function as drivers of aggregation in condensates.}, } @article {pmid39171600, year = {2025}, author = {Nogueira-Machado, JA and das Chagas Lima E Silva, F and Rocha-Silva, F and Gomes, N}, title = {Amyotrophic Lateral Sclerosis (ALS): An Overview of Genetic and Metabolic Signaling Mechanisms.}, journal = {CNS & neurological disorders drug targets}, volume = {24}, number = {2}, pages = {83-90}, pmid = {39171600}, issn = {1996-3181}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/metabolism ; *Signal Transduction/genetics/physiology ; Mutation/genetics ; Animals ; }, abstract = {Amyotrophic Lateral Sclerosis (ALS) is a rare, progressive, and incurable disease. Sporadic (sALS) accounts for ninety percent of ALS cases, while familial ALS (fALS) accounts for around ten percent. Reports have identified over 30 different forms of familial ALS. Multiple types of fALS exhibit comparable symptoms with mutations in different genes and possibly with different predominant metabolic signals. Clinical diagnosis takes into account patient history but not genetic mutations, misfolded proteins, or metabolic signaling. As research on genetics and metabolic pathways advances, it is expected that the intricate complexity of ALS will compound further. Clinicians discuss whether a gene's presence is a cause of the disease or just an association or consequence. They believe that a mutant gene alone is insufficient to diagnose ALS. ALS, often perceived as a single disease, appears to be a complex collection of diseases with similar symptoms. This review highlights gene mutations, metabolic pathways, and muscle-neuron interactions.}, } @article {pmid39170988, year = {2024}, author = {Baroni, LM and Funari, MP and So Taa Kum, A and Bestetti, AM and de Oliveira, LB and de Carvalho, MF and Franzini, TAP and de Moura, DTH and Bernardo, WM and de Moura, EGH}, title = {Endoscopic Versus Surgical Treatment for Ampullary Lesions: A Systematic Review With Meta-Analysis.}, journal = {Cureus}, volume = {16}, number = {7}, pages = {e65076}, pmid = {39170988}, issn = {2168-8184}, abstract = {Ampullary lesions (ALs) can be treated through either an endoscopic approach (EA) or a surgical approach (SA). However, it is important to note that EAs carry a significant risk of incomplete resection, while opting for surgical interventions can result in substantial morbidity. We performed a systematic review and meta-analysis for R0 resection, recurrence, adverse events in general, major adverse events, mortality, and length of hospital stay between SAs and EAs. Electronic databases were searched from inception to 2023. We identified nine independent studies. The risk difference was -0.32 (95% CI: -0.50, -0.15; p <0.001) for R0, 0.12 (95% CI: 0.06, 0.19; p < 0.001) for recurrence, -0.22 (95% CI: -0.43, 0.00; p 0.05) for overall adverse events, -0.11 (95% CI: -0.32, 0.10; p = 0.31) for major complications, -0.01 (95% CI: -0.02, 0.01; p = 0.43) for mortality, and -14.69 (95% CI: -19.91, -9.47; p < 0.001) for length of hospital stay. As expected, our data suggest a higher complete resection rate and lower recurrence from surgical interventions, but this is associated with an elevated risk of adverse events and a longer hospital stay.}, } @article {pmid39170265, year = {2024}, author = {Pain, O and Jones, A and Al Khleifat, A and Agarwal, D and Hramyka, D and Karoui, H and Kubica, J and Llewellyn, DJ and Ranson, JM and Yao, Z and Iacoangeli, A and Al-Chalabi, A}, title = {Harnessing transcriptomic signals for amyotrophic lateral sclerosis to identify novel drugs and enhance risk prediction.}, journal = {Heliyon}, volume = {10}, number = {15}, pages = {e35342}, pmid = {39170265}, issn = {2405-8440}, support = {MR/R024804/1/MRC_/Medical Research Council/United Kingdom ; }, abstract = {INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease. This study integrates common genetic association results from the latest ALS genome-wide association study (GWAS) summary statistics with functional genomic annotations with the aim of providing mechanistic insights into ALS risk loci, inferring drug repurposing opportunities, and enhancing prediction of ALS risk and clinical characteristics.

METHODS: Genes associated with ALS were identified using GWAS summary statistic methodology including SuSiE SNP-based fine-mapping, and transcriptome- and proteome-wide association study (TWAS/PWAS) analyses. Using several approaches, gene associations were integrated with the DrugTargetor drug-gene interaction database to identify drugs that could be repurposed for the treatment of ALS. Furthermore, ALS gene associations from TWAS were combined with observed blood expression in two external ALS case-control datasets to calculate polytranscriptomic scores and evaluate their utility for prediction of ALS risk and clinical characteristics, including site of onset, age at onset, and survival.

RESULTS: SNP-based fine-mapping, TWAS and PWAS identified 118 genes associated with ALS, with TWAS and PWAS providing novel mechanistic insights. Drug repurposing analyses identified six drugs significantly enriched for interactions with ALS associated genes, though directionality could not be determined. Additionally, drug class enrichment analysis showed gene signatures linked to calcium channel blockers may reduce ALS risk, whereas antiepileptic drugs may increase ALS risk. Across the two observed expression target samples, ALS polytranscriptomic scores significantly predicted ALS risk (R [2] = 5.1 %; p-value = 3.2 × 10[-27]) and clinical characteristics.

CONCLUSIONS: Functionally-informed analyses of ALS GWAS summary statistics identified novel mechanistic insights into ALS aetiology, highlighted several therapeutic research avenues, and enabled statistically significant prediction of ALS risk.}, } @article {pmid39170125, year = {2024}, author = {Wenzhi, Y and Xiangyi, L and Dongsheng, F}, title = {The prion-like effect and prion-like protein targeting strategy in amyotrophic lateral sclerosis.}, journal = {Heliyon}, volume = {10}, number = {15}, pages = {e34963}, pmid = {39170125}, issn = {2405-8440}, abstract = {Pathological proteins in amyotrophic lateral sclerosis (ALS), such as superoxide dismutase 1, TAR DNA-binding protein 43, and fused in sarcoma, exhibit a prion-like pattern. All these proteins have a low-complexity domain and seeding activity in cells. In this review, we summarize the studies on the prion-like effect of these proteins and list six prion-like protein targeting strategies that we believe have potential for ALS therapy, including antisense oligonucleotides, antibody-based technology, peptide, protein chaperone, autophagy enhancement, and heteromultivalent compounds. Considering the pathological complexity and heterogeneity of ALS, we believe that the final solution to ALS therapy is most likely to be an individualized cocktail therapy, including clearance of toxicity, blockage of pathological progress, and protection of neurons.}, } @article {pmid39170062, year = {2024}, author = {Wang, H and Yao, G and He, K and Wang, Z and Cheng, CK}, title = {ACL reconstruction combined with anterolateral structures reconstruction for treating ACL rupture and knee injuries: a finite element analysis.}, journal = {Frontiers in bioengineering and biotechnology}, volume = {12}, number = {}, pages = {1437684}, pmid = {39170062}, issn = {2296-4185}, abstract = {Introduction: The biomechanical indication for combining anterolateral structures reconstruction (ASLR) with ACL reconstruction (ACLR) to reduce pivot shift in the knee remains unclear. This study aims to investigate knee functionality after ACL rupture with different combinations of injuries, and to compare the effectiveness of ALSR with ACLR for treating these injuries. Methods: A validated finite element model of a human cadaveric knee was used to simulate pivot shift tests on the joint in different states, including 1) an intact knee; 2) after isolated ACL rupture; 3) after ACL rupture combined with different knee injuries or defect, including a posterior tibial slope (PTS) of 20°, an injury to the anterolateral structures (ALS) and an injury to the posterior meniscotibial ligament of the lateral meniscus (LP); 4) after treating the different injuries using isolated ACLR; v. after treating the different injuries using ACLR with ALSR. The knee kinematics, maximum von Mises stress (Max.S) on the tibial articular cartilage (TC) and force in the ACL graft were compared among the different simulation groups. Results and discussion: Comparing with isolated ACL rupture, combined injury to the ALS caused the largest knee laxity, when a combined PTS of 20° induced the largest Max.S on the TC. The joint stability and Max.S on the TC in the knee with an isolated ACL rupture or a combined rupture of ACL and LP were restored to the intact level after being treated with isolated ACLR. The knee biomechanics after a combined rupture of ACL and ALS were restored to the intact level only when being treated with a combination of ACLR and ALSR using a large graft diameter (6 mm) for ALSR. However, for the knee after ACL rupture combined with a PTS of 20°, the ATT and Max.S on the TC were still greater than the intact knee even after being treated with a combination of ACLR and ALSR. The finite element analysis showed that ACLR should include ALSR when treating ACL ruptures accompanied by ALS rupture. However, pivot shift in knees with a PTS of 20° was not eliminated even after a combined ACLR and ALSR.}, } @article {pmid39168583, year = {2024}, author = {Memudu, AE and Olukade, BA and Adebayo, OS and Raza, ML}, title = {Coffee and amyotrophic lateral sclerosis (ALS).}, journal = {Progress in brain research}, volume = {289}, number = {}, pages = {81-105}, doi = {10.1016/bs.pbr.2024.06.003}, pmid = {39168583}, issn = {1875-7855}, mesh = {*Amyotrophic Lateral Sclerosis/pathology ; Humans ; *Coffee ; Animals ; Neuroprotective Agents/pharmacology ; Oxidative Stress/physiology/drug effects ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder characterized by progressive loss of motor neurons. The effective treatments for ALS remain elusive, necessitating exploration into novel preventive strategies. ALS pathogenesis is triggered by oxidative stress which results in neuroinflammation, exicitotoxicity and neuronal cell death. Nutritional mechanism for halting progression of neurodegeneration is through dietary compounds with antioxidants, anti-inflammatory or neuromodulating activity. Coffee is a widely consumed beverage made up of polyphenols, caffeine and other compounds with possible antioxidants and neuro-protective roles. It is important to say that various epidemiological studies have documented association between coffee intake and ALS. This chapter is aimed to present a comprehensive review of existing literature on coffee consumption and ALS, involving epidemiological studies, preclinical research, and its mechanism of actions in animal model of ALS. It highlights key findings regarding the potential neuroprotective properties of coffee constituents such as caffeine, polyphenols, and other bioactive compounds. Furthermore, it discusses possible pathways through which coffee may modulate ALS pathogenesis, including suppressing oxidative stress and neuroinflammation while boosting adenosine function via the adenosine receptor two on the motor neuron cells membrane in the spinal cord to enhance motor function via the corticospinal tract. Overall, this chapter underscores the significance of further research to unravel the specific mechanisms by which coffee exerts its neuroprotective effects in ALS, with the ultimate goal of identifying dietary strategies for ALS prevention and management.}, } @article {pmid39168577, year = {2024}, author = {Rai, SP and Ansari, AH and Singh, D and Singh, S}, title = {Coffee, antioxidants, and brain inflammation.}, journal = {Progress in brain research}, volume = {289}, number = {}, pages = {123-150}, doi = {10.1016/bs.pbr.2024.06.005}, pmid = {39168577}, issn = {1875-7855}, mesh = {*Coffee/chemistry ; Humans ; *Antioxidants/pharmacology ; Animals ; Neurodegenerative Diseases ; Encephalitis ; Caffeine/pharmacology/administration & dosage ; Neuroinflammatory Diseases ; }, abstract = {Coffee is the most popular beverage in the world and, aside from tea and water, the most often consumed caffeine-containing beverage. Because of its high caffeine concentration, it is typically classified as a stimulant. There are other bioactive ingredients in coffee besides caffeine. The coffee beverage is a blend of several bioactive substances, including diterpenes (cafestol and kahweol), alkaloids (caffeine and trigonelline), and polyphenols (particularly chlorogenic acids in green beans and caffeic acid in roasted coffee beans). Caffeine has also been linked to additional beneficial benefits such as antioxidant and anti-inflammatory properties, which change cellular redox and inflammatory status in a dose-dependent manner. Pyrocatechol, a constituent of roasted coffee that is created when chlorogenic acid is thermally broken down, has anti-inflammatory properties as well. It is postulated that coffee consumption reduces neuroinflammation, which is intimately linked to the onset of neurodegenerative disorders like Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD). This review provides an overview of the most recent studies regarding coffee's possible benefits in preventing brain inflammation and neurodegenerative disorders.}, } @article {pmid39168358, year = {2024}, author = {Ueno, Y and Morishima, Y and Hata, T and Shindo, A and Murata, H and Saito, T and Nakamura, Y and Shindo, K}, title = {Current progress in microRNA profiling of circulating extracellular vesicles in amyotrophic lateral sclerosis: A systematic review.}, journal = {Neurobiology of disease}, volume = {200}, number = {}, pages = {106639}, doi = {10.1016/j.nbd.2024.106639}, pmid = {39168358}, issn = {1095-953X}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/blood/genetics/diagnosis ; Biomarkers/blood ; *Extracellular Vesicles/metabolism/genetics ; *MicroRNAs/blood/genetics ; }, abstract = {INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease affecting upper and lower motor neurons, leading to death resulting mainly from respiratory failure, for which there is currently no curative treatment. Underlying pathological mechanisms for the development of ALS are diverse and have yet to be elucidated. Non-invasive testing to isolate circulating molecules including microRNA to diagnose ALS has been reported, but circulating extracellular vesicle (EV)-derived microRNA has not been fully studied in the ALS population.

METHODS: A systematic literature review to explore studies investigating the profile of microRNAs in EVs from blood samples of ALS patients was carried out according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline.

RESULTS: Eleven studies including a total of 263 patients with ALS were included in the present systematic review. The majority of patients had sporadic ALS, though a small number of patients with ALS having genetic mutations were included. Seven studies used plasma-derived EVs, and the remaining four studies used serum-derived EVs. RNA sequencing or microarrays were used in eight studies, and quantitative PCR was used in eight studies, of which five studies used RNA sequencing or microarrays for screening and quantitative PCR for validation. There was overlap of miR-199a-3p and miR-199a-5p in three studies.

CONCLUSIONS: Overall, the systematic review addressed the current advances in the profiling of microRNAs in circulating EVs of ALS patients. Blood samples, isolation of EVs, and microRNA analysis were diverse. Although there was an overlap of miR-199a-3p and miR-199a-5p, collection of further evidence is warranted.}, } @article {pmid39167487, year = {2024}, author = {Alirzayeva, H and Loureiro, R and Koyuncu, S and Hommen, F and Nabawi, Y and Zhang, WH and Dao, TTP and Wehrmann, M and Lee, HJ and Vilchez, D}, title = {ALS-FUS mutations cause abnormal PARylation and histone H1.2 interaction, leading to pathological changes.}, journal = {Cell reports}, volume = {43}, number = {8}, pages = {114626}, doi = {10.1016/j.celrep.2024.114626}, pmid = {39167487}, issn = {2211-1247}, mesh = {*Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology ; Humans ; *Histones/metabolism ; *RNA-Binding Protein FUS/metabolism/genetics ; *Caenorhabditis elegans/metabolism/genetics ; Animals ; *Mutation/genetics ; *Poly (ADP-Ribose) Polymerase-1/metabolism/genetics ; Motor Neurons/metabolism/pathology ; Poly ADP Ribosylation ; Induced Pluripotent Stem Cells/metabolism ; Protein Binding ; }, abstract = {The majority of severe early-onset and juvenile cases of amyotrophic lateral sclerosis (ALS) are caused by mutations in the FUS gene, resulting in rapid disease progression. Mutant FUS accumulates within stress granules (SGs), thereby affecting the dynamics of these ribonucleoprotein complexes. Here, we define the interactome of the severe mutant FUS[P525L] variant in human induced pluripotent stem cell (iPSC)-derived motor neurons. We find increased interaction of FUS[P525L] with the PARP1 enzyme, promoting poly-ADP-ribosylation (PARylation) and binding of FUS to histone H1.2. Inhibiting PARylation or reducing H1.2 levels alleviates mutant FUS aggregation, SG alterations, and apoptosis in human motor neurons. Conversely, elevated H1.2 levels exacerbate FUS-ALS phenotypes, driven by the internally disordered terminal domains of H1.2. In C. elegans models, knockdown of H1.2 and PARP1 orthologs also decreases FUS[P525L] aggregation and neurodegeneration, whereas H1.2 overexpression worsens ALS-related changes. Our findings indicate a link between PARylation, H1.2, and FUS with potential therapeutic implications.}, } @article {pmid39167140, year = {2024}, author = {Yu, L and Wu, N and Choi, O and Nguyen, KD}, title = {Inhibition of glycolytic reprogramming suppresses innate immune-mediated inflammation in experimental amyotrophic lateral sclerosis.}, journal = {Inflammation research : official journal of the European Histamine Research Society ... [et al.]}, volume = {73}, number = {11}, pages = {1847-1857}, pmid = {39167140}, issn = {1420-908X}, mesh = {Animals ; *Amyotrophic Lateral Sclerosis/immunology/drug therapy ; *Immunity, Innate/drug effects ; *Glycolysis/drug effects ; *Spinal Cord/immunology/pathology/drug effects/metabolism ; *Mice, Transgenic ; Mice ; Inflammation ; Male ; Disease Models, Animal ; Monocytes/drug effects/immunology ; Mice, Inbred C57BL ; Microglia/drug effects/immunology/metabolism ; Female ; }, abstract = {BACKGROUND: Innate immune activation has been implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS). However, metabolic pathways that govern this bioenergetically demanding process in ALS remains elusive. Here we investigated whether and how immunometabolic transformation of innate immune cells contributes to disease progression in an experimental model of this neurodegenerative disease.

METHODS: We utilized multidimensional flow cytometry and integrative metabolomics to characterize the immunometabolic phenotype of circulating and spinal cord innate immune cells in the B6SJL-Tg(SOD1*G93A)1Gur/J model of ALS (SOD1-G93A) at various disease stages (before vs. after the onset of motor dysfunction). Behavioral and survival analyses were also conducted to determine the impact of an energy-regulating compound on innate immune cell metabolism, inflammation, and disease development.

RESULTS: Temporally coordinated accumulation of circulating inflammatory Ly6C + monocytes and spinal cord F4/80 + CD45[hi] infiltrates precedes the onset of motor dysfunction in SOD1-G93A mice. Subsequent metabolomic analysis reveals that this phenomenon is accompanied by glycolytic reprogramming of spinal cord inflammatory CD11b + cells, comprising both resident F4/80 + CD45[low] microglia and F4/80 + CD45[hi] infiltrates. Furthermore, pharmacologic inhibition of glycolysis by ZLN005, a small molecule activator of Ppargc1a, restrains inflammatory glycolytic activation of spinal cord CD11b + cells, enhances motor function, and prolongs survival in SOD1-G93A mice.

CONCLUSIONS: These observations suggest that modulation of inflammatory glycolytic reprogramming of innate immune cells may represent a promising therapeutic approach in ALS.}, } @article {pmid39163164, year = {2025}, author = {Raggi, A and Serretti, A and Ferri, R}, title = {The P300 component of the auditory event-related potential in adult psychiatric and neurologic disorders: a narrative review of clinical and experimental evidence.}, journal = {International clinical psychopharmacology}, volume = {40}, number = {5}, pages = {259-274}, doi = {10.1097/YIC.0000000000000566}, pmid = {39163164}, issn = {1473-5857}, mesh = {Humans ; *Event-Related Potentials, P300/physiology ; *Mental Disorders/physiopathology/diagnosis ; *Nervous System Diseases/physiopathology/diagnosis ; *Evoked Potentials, Auditory/physiology ; Adult ; Electroencephalography ; Neuropsychological Tests ; }, abstract = {The auditory P300 wave, also known as P3b, is an event-related potential component thought to reflect central information processes involved in stimulus evaluation or categorization. It is typically elicited using the oddball paradigm, which involves mixing low-probability target items with high-probability standard stimuli. Its latency is associated with the timing of cognitive processes such as stimulus evaluation and response preparation, while its amplitude is related to the amount of attentional resources engaged during the task. Despite decades of use in research settings, its application in clinical practice has been limited. Prolongation of latencies and reduction of amplitudes in the auditory P3b have been observed in both psychiatric and neurological conditions. This includes cases where traditional neuropsychological tests are challenging due to severe motor or speech dysfunctions, or in conditions characterized by subtle cognitive deficits. Additionally, specific laterality patterns in psychoses and a loss of P300 habituation in migraines have been described. The wealth of experimental evidence supports the use of this evoked potential, which can be elicited through a relatively simple paradigm, for objectively evaluating cognition in psychiatric and neurological patients, particularly in follow-up assessments. Therefore, the auditory P300 appears to be a valuable tool for monitoring the clinical course of patients with mental and neurological disorders in certain circumstances.}, } @article {pmid39163160, year = {2024}, author = {Purcell, N and Manousakis, G}, title = {Diverse Phenotypic Presentation of the Welander Distal Myopathy Founder Mutation, With Myopathy and Amyotrophic Lateral Sclerosis in the Same Family.}, journal = {Journal of clinical neuromuscular disease}, volume = {26}, number = {1}, pages = {42-46}, doi = {10.1097/CND.0000000000000501}, pmid = {39163160}, issn = {1537-1611}, mesh = {Female ; Humans ; Middle Aged ; *Amyotrophic Lateral Sclerosis/genetics ; *Distal Myopathies/genetics/diagnosis ; Founder Effect ; *Mutation ; *Pedigree ; *Phenotype ; T-Cell Intracellular Antigen-1/genetics ; Aged ; Aged, 80 and over ; }, abstract = {Welander distal myopathy is a rare myopathy with prominent and early involvement of distal upper extremity muscles, prevalent in individuals of Scandinavian origin, and caused by a founder mutation in the cytotoxic granule-associated RNA-binding protein (T-cell intracellular antigen-1; TIA1), E384K. Different pathogenic variants in the TIA1 gene, distinct from the founder 1, have recently been associated with frontotemporal dementia and amyotrophic lateral sclerosis (ALS), suggesting that TIA1-related disorders belong to the group of multisystem proteinopathies. We describe the first case of a two-generation family with the founder E384K TIA1 mutation demonstrating phenotypic variability; the mother manifested as Welander myopathy, whereas 2 daughters manifested as ALS. No other genetic cause of ALS was found in 1 of the affected daughters. We also discuss the possible mechanisms explaining this pleotropic presentation of the founder mutation.}, } @article {pmid39163156, year = {2024}, author = {Takahashi, K and Hamada, Y and Kobayashi, M and Kobayashi, S and Kanbayashi, T and Hatanaka, Y and Nakayama, T and Imafuku, I and Matsuno, H and Iguchi, Y and Katada, F and Fukutake, T and Ando, T and Mikata, T and Usui, T and Uchino, K and Nishiyama, K and Sonoo, M}, title = {Utility of the Repetitive Nerve Stimulation Test and Needle EMG in the Trapezius Muscle for the Early Diagnosis of ALS.}, journal = {Journal of clinical neuromuscular disease}, volume = {26}, number = {1}, pages = {1-11}, doi = {10.1097/CND.0000000000000479}, pmid = {39163156}, issn = {1537-1611}, support = {19K07966 and 22K07524//Ministry of Education, Science, Sports and Culture of Japan/ ; 19ek0109252h0003//AMED/ ; }, mesh = {Humans ; *Electromyography/methods ; Male ; Female ; Middle Aged ; *Amyotrophic Lateral Sclerosis/physiopathology/diagnosis ; Aged ; Retrospective Studies ; *Electric Stimulation ; *Superficial Back Muscles/physiopathology ; *Sensitivity and Specificity ; Adult ; Early Diagnosis ; }, abstract = {OBJECTIVES: To document the utility of decremental responses in the repetitive nerve stimulation test (RNS) and spontaneous activities in needle electromyography (EMG) in the trapezius muscle for the diagnosis of amyotrophic lateral sclerosis.

METHODS: Subjects were retrospectively identified from our EMG database. Cervical spondylosis was represented as a disease control group. We investigated the sensitivity and specificity of RNS and EMG in the trapezius muscle and those of diagnostic criteria including the Gold Coast criteria (GCC).

RESULTS: We reviewed 120 patients with amyotrophic lateral sclerosis and 17 patients with cervical spondylosis. "RNS or EMG" achieved the highest sensitivity (85%). The specificity was the highest for RNS (94%). Addition of RNS of the deltoid muscle achieved 98% sensitivity in the upper-limb onset amyotrophic lateral sclerosis. The sensitivity of the GCC was very high (88%).

CONCLUSIONS: Neurophysiological parameters investigated in this study having close to 100% specificities or sensitivities are useful as complements to the GCC.}, } @article {pmid39163111, year = {2025}, author = {Fenoy, A}, title = {Scientific plurality and amyotrophic lateral sclerosis (ALS): A philosophical and historical perspective on Charcot's texts.}, journal = {Journal of the history of the neurosciences}, volume = {34}, number = {2}, pages = {133-142}, doi = {10.1080/0964704X.2024.2380635}, pmid = {39163111}, issn = {1744-5213}, mesh = {*Amyotrophic Lateral Sclerosis/history ; Humans ; History, 20th Century ; History, 19th Century ; }, abstract = {The history of amyotrophic lateral sclerosis (ALS)-also known as Charcot's disease, Lou Gehrig's disease, and motor neuron disease (MND)-freezes the texts of the scientist and physician Jean-Martin Charcot in a hagiographic narrative describing a brilliant discovery, based on the anatomo-clinical method. This narrative is often used by biologists and physicians as a reference point. This article shows that the use of the hagiographic register faces limitations. In particular, it obscures points of interest from Charcot's texts on ALS, such as the epistemological and ontological implications of scientific plurality in medicine. Although Charcot recognized the importance of scientific plurality in medicine, he prioritized the approaches and conferred the most important epistemic authority on clinical and pathological observations. In his view, animal modeling remains secondary to the understanding of disease. The concept of ALS and its diagnostic operability are the result of symptoms and lesions. By studying the past, we can highlight the specific features of the present. Today, although the ALS concept retains its diagnostic and clinical relevance, it is increasingly called into question in etiological and mechanistic research. Despite these differences, Charcot's reflections are a reminder of the importance of theoretical thinking on scientific plurality, all the more so today in the context of ALS research, in which combining different approaches is increasingly valued to understand the phenotypic and genetic heterogeneity of ALS.}, } @article {pmid39162129, year = {2024}, author = {Mazzini, L and De Marchi, F and Buzanska, L and Follenzi, A and Glover, JC and Gelati, M and Lombardi, I and Maioli, M and Mesa-Herrera, F and Mitrečić, D and Olgasi, C and Pivoriūnas, A and Sanchez-Pernaute, R and Sgromo, C and Zychowicz, M and Vescovi, A and Ferrari, D}, title = {Current status and new avenues of stem cell-based preclinical and therapeutic approaches in amyotrophic lateral sclerosis.}, journal = {Expert opinion on biological therapy}, volume = {24}, number = {9}, pages = {933-954}, doi = {10.1080/14712598.2024.2392307}, pmid = {39162129}, issn = {1744-7682}, mesh = {*Amyotrophic Lateral Sclerosis/therapy/genetics ; Humans ; Animals ; *Stem Cell Transplantation ; Disease Models, Animal ; Clinical Trials as Topic ; }, abstract = {INTRODUCTION: Cell therapy development represents a critical challenge in amyotrophic lateral sclerosis (ALS) research. Despite more than 20 years of basic and clinical research, no definitive safety and efficacy results of cell-based therapies for ALS have been published.

AREAS COVERED: This review summarizes advances using stem cells (SCs) in pre-clinical studies to promote clinical translation and in clinical trials to treat ALS. New technologies have been developed and new experimental in vitro and animal models are now available to facilitate pre-clinical research in this field and to determine the most promising approaches to pursue in patients. New clinical trial designs aimed at developing personalized SC-based treatment with biological endpoints are being defined.

EXPERT OPINION: Knowledge of the basic biology of ALS and on the use of SCs to study and potentially treat ALS continues to grow. However, a consensus has yet to emerge on how best to translate these results into therapeutic applications. The selection and follow-up of patients should be based on clinical, biological, and molecular criteria. Planning of SC-based clinical trials should be coordinated with patient profiling genetically and molecularly to achieve personalized treatment. Much work within basic and clinical research is still needed to successfully transition SC therapy in ALS.}, } @article {pmid39161942, year = {2024}, author = {Marcu, IR and Rogoveanu, OC and Pădureanu, R and Pădureanu, V and Dop, D}, title = {Diagnostic elements in amyotrophic lateral sclerosis: A case report.}, journal = {Biomedical reports}, volume = {21}, number = {4}, pages = {141}, pmid = {39161942}, issn = {2049-9442}, abstract = {Amyotrophic lateral sclerosis (ALS) is a rare neurological disease that involves the degeneration of both upper and lower motor neurons responsible for controlling voluntary muscle activity. Most people with ALS die within 3-5 years due to respiratory failure. The current study presents the case of a 68-year-old woman diagnosed with ALS based on the subjective and objective findings from the patient's initial physiotherapy assessment and on neurophysiological tests. Physiotherapy interventions are aiming to maintain the patient's strength, balance and functional independence for as long as possible. The present case report aimed to highlight that a multidisciplinary team approach is necessary for the management of a progressive degenerative disease such as ALS.}, } @article {pmid39158304, year = {2024}, author = {Tong, Z and Zhang, X and Guo, X and Wu, G and Cao, S and Zhang, Y and Meng, X and Wang, T and Wang, Y and Song, Y and Yang, R and Du, Z}, title = {Delivery of Yersinia pestis antigens via Escherichia coli outer membrane vesicles offered improved protection against plague.}, journal = {mSphere}, volume = {9}, number = {9}, pages = {e0033024}, pmid = {39158304}, issn = {2379-5042}, support = {2022YFC2303503//National Key Research and Development of China/ ; 32070136//MOST | National Natural Science Foundation of China (NSFC)/ ; }, mesh = {Animals ; *Plague/prevention & control/immunology ; *Antigens, Bacterial/immunology/genetics ; *Bacterial Outer Membrane Proteins/immunology/genetics ; *Escherichia coli/genetics/immunology ; *Yersinia pestis/immunology/genetics ; Mice ; *Pore Forming Cytotoxic Proteins/immunology/genetics ; *Plague Vaccine/immunology/administration & dosage/genetics ; Female ; *Antibodies, Bacterial/blood/immunology ; Mice, Inbred BALB C ; Recombinant Fusion Proteins/immunology/genetics ; Bacterial Outer Membrane/immunology ; Bacterial Proteins ; }, abstract = {Outer membrane vesicles (OMVs) from Gram-negative bacteria can be used as a vaccine platform to deliver heterologous antigens. Here, the major protective antigens of Yersinia pestis, F1 and LcrV, were fused either with the leader sequence or the transmembrane domain of the outer membrane protein A (OmpA), resulting in chimeric proteins OmpA-ls-F1V and OmpA46-159-F1V, respectively. We show that OmpA-ls-F1V and OmpA46-159-F1V can be successfully delivered into the lumen and membrane of the OMVs of Escherichia coli, respectively. Mutation of ompA but not tolR in E. coli enhanced the delivery efficiency of OmpA-ls-F1V into OMVs. The OmpA-ls-F1V protein comprises up to 20% of the total protein in OMVs derived from the ompA mutant (OMVdA-ALS-F1V), a proportion significantly higher than the 1% observed for OmpA46-159-F1V in OMVs produced by an ompA mutant that expresses OmpA46-159-F1V, referred to as OMVdA-LATM5-F1V. Intramuscular (i.m.) immunization of mice with OMVdA-ALS-F1V induced significantly higher levels of serum anti-LcrV and anti-F1 IgG, and provided higher efficacy in protection against subcutaneous (s.c.) Y. pestis infection compared to OMVdA-LATM5-F1V and the purified recombinant F1V (rF1V) protein adsorbed to aluminum hydroxide. The three-dose i.m. immunization with OMVdA-ALS-F1V, administered at 14-day intervals, provides complete protection to mice against s.c. infection with 130 LD50 of Y. pestis 201 and conferred 80% against intranasal (i.n.) challenge with 11.4 LD50 of Y. pestis 201. Taken together, our findings indicate that the engineered OMVs containing F1V fused with the leader sequence of OmpA provide significantly higher protection than rF1V against both s.c. and i.n. infection of Y. pestis and more balanced Th1/Th2 responses.IMPORTANCEThe two major protective antigens of Y. pestis, LcrV and F1, have demonstrated the ability to elicit systemic and local mucosal immune responses as subunit vaccines. However, these vaccines have failed to provide adequate protection against pneumonic plague in African green monkeys. Here, Y. pestis F1 and LcrV antigens were successfully incorporated into the lumen and the surface of the outer membrane vesicles (OMVs) of E. coli by fusion either with the leader sequence or the transmembrane domain of OmpA. We compared the humoral immune response elicited by these OMV formulations and their protective efficacy in mice against Y. pestis. Our results demonstrate that the plague OMV vaccine candidates can induce robust protective immunity against both s.c. and i.n. Y. pestis infections, surpassing the effectiveness of rF1V. In addition, immunization with OMVs generated a relatively balanced Th1/Th2 immune response compared to rF1V immunization. These findings underscore the potential of OMVs-based plague vaccines for further development.}, } @article {pmid39157517, year = {2024}, author = {Zhang, Y and Zhang, Q and Liu, Q and Zhao, Y and Xu, W and Hong, C and Xu, C and Qi, X and Qi, X and Liu, B}, title = {Fine mapping and functional validation of the maize nicosulfuron-resistance gene CYP81A9.}, journal = {Frontiers in plant science}, volume = {15}, number = {}, pages = {1443413}, pmid = {39157517}, issn = {1664-462X}, abstract = {Nicosulfuron, a widely utilized herbicide, is detrimental to some maize varieties due to their sensitivity. Developing tolerant varieties with resistance genes is an economical and effective way to alleviate phytotoxicity. In this study, map-based cloning revealed that the maize resistance gene to nicosulfuron is Zm00001eb214410 (CYP81A9), which encodes a cytochrome P450 monooxygenase. qRT- PCR results showed that CYP81A9 expression in the susceptible line JS188 was significantly reduced compared to the resistant line B73 during 0-192 hours following 80 mg/L nicosulfuron spraying. Meanwhile, a CYP81A9 overexpression line exhibited normal growth under a 20-fold nicosulfuron concentration (1600 mg/L), while the transgenic acceptor background material Zong31 did not survive. Correspondingly, silencing CYP81A9 through CRISPR/Cas9 mutagenesis and premature transcription termination mutant EMS4-06e182 resulted in the loss of nicosulfuron resistance in maize. Acetolactate Synthase (ALS), the target enzyme of nicosulfuron, exhibited significantly reduced activity in the roots, stems, and leaves of susceptible maize post-nicosulfuron spraying. The CYP81A9 expression in the susceptible material was positively correlated with ALS activity in vivo. Therefore, this study identified CYP81A9 as the key gene regulating nicosulfuron resistance in maize and discovered three distinct haplotypes of CYP81A9, thereby laying a solid foundation for further exploration of the underlying resistance mechanisms.}, } @article {pmid39156974, year = {2024}, author = {Fenili, G and Scaricamazza, S and Ferri, A and Valle, C and Paronetto, MP}, title = {Physical exercise in amyotrophic lateral sclerosis: a potential co-adjuvant therapeutic option to counteract disease progression.}, journal = {Frontiers in cell and developmental biology}, volume = {12}, number = {}, pages = {1421566}, pmid = {39156974}, issn = {2296-634X}, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal disorder characterized by the selective degeneration of upper and lower motor neurons, leading to progressive muscle weakness and atrophy. The mean survival time is two to five years. Although the hunt for drugs has greatly advanced over the past decade, no cure is available for ALS yet. The role of intense physical activity in the etiology of ALS has been debated for several decades without reaching a clear conclusion. The benefits of organized physical activity on fitness and mental health have been widely described. Indeed, by acting on specific mechanisms, physical activity can influence the physiology of several chronic conditions. It was shown to improve skeletal muscle metabolism and regeneration, neurogenesis, mitochondrial biogenesis, and antioxidant defense. Interestingly, all these pathways are involved in ALS pathology. This review will provide a broad overview of the effect of different exercise protocols on the onset and progression of ALS, both in humans and in animal models. Furthermore, we will discuss challenges and opportunities to exploit physiological responses of imposed exercise training for therapeutic purposes.}, } @article {pmid39156432, year = {2024}, author = {Kaye, AD and Sala, KR and Dethloff, D and Norton, M and Moss, C and Plessala, MJ and Derouen, AG and Lopez Torres, Y and Kim, J and Tirumala, S and Shekoohi, S and Varrassi, G}, title = {The Evolving Use of Gold Nanoparticles as a Possible Reversal Agent for the Symptoms of Neurodegenerative Diseases: A Narrative Review.}, journal = {Cureus}, volume = {16}, number = {7}, pages = {e64846}, pmid = {39156432}, issn = {2168-8184}, abstract = {Neurodegenerative diseases are broadly hallmarked by impaired energy metabolism and toxic intracellular accumulations such as damaged organelles or reactive oxygen species (ROS). Gold nanoparticles readily cross the blood-brain barrier and increase nicotinamide adenine dinucleotide + hydrogen (NADH) oxidation to nicotinamide adenine dinucleotide (NAD+), which is vital for intracellular energy generation, cellular repair, and protection from ROS. Thus, the use of gold nanoparticles to treat and potentially reverse cellular injury seen in neurodegenerative disease has been an area of ongoing research. This systematic review explores current literature regarding the use of gold nanoparticle therapy in the treatment of neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS). In vitro studies of CNM-Au8 (Clene Nanomedicine, Salt Lake City, UT) have been shown to reduce TDP-43 aggregates associated with ALS. These studies also exhibited the neuroprotective effects of CNM-Au8 in rat primary neurons exposed to amyloid-beta peptides, which are associated with Alzheimer's disease. In animal models of MS, oral delivery of CNM-Au8 was demonstrated to produce robust and significant remyelination activity, oligodendrocyte maturation, and expression of myelin markers. In these same MS animal models, CNM-Au8 improved the motor function of cuprizone-treated mice in both open-field and kinematic gait studies. Recent phase II trials of CNM-Au8 in 13 patients with Parkinson's disease and 11 patients with stable relapsing MS demonstrated a statistically significant increase in the NAD+/NADH ratio across two cohorts. As the current data repeatedly suggest, these gold nanoparticles are efficacious for the treatment and reversal of symptoms across these varying neurodegenerative pathologies. Further opportunities exist for increasing human trials and eventually incorporating this new technology into existing treatment regimens.}, } @article {pmid39154890, year = {2024}, author = {Brebner, C and Asamoah-Boaheng, M and Zaidel, B and Yap, J and Scheuermeyer, F and Mok, V and Hutton, J and Meckler, G and Schlamp, R and Christenson, J and Grunau, B}, title = {The association of intravenous vs. humeral-intraosseous vascular access with patient outcomes in adult out-of-hospital cardiac arrests.}, journal = {Resuscitation}, volume = {202}, number = {}, pages = {110360}, doi = {10.1016/j.resuscitation.2024.110360}, pmid = {39154890}, issn = {1873-1570}, mesh = {Humans ; *Out-of-Hospital Cardiac Arrest/therapy/mortality ; Male ; Female ; *Infusions, Intraosseous/methods ; Middle Aged ; *Cardiopulmonary Resuscitation/methods ; *Registries ; Aged ; Humerus ; Emergency Medical Services/methods ; Treatment Outcome ; Adult ; Propensity Score ; }, abstract = {AIM: While intravenous (IV) vascular access for out-of-hospital cardiac arrest (OHCA) resuscitation is standard, humeral-intraosseous (IO) access is commonly used, despite few supporting data. We investigated the association between IV vs. humeral-IO and outcomes.

METHODS: We utilized BC Cardiac Arrest Registry data, including adult OHCA where the first-attempted intra-arrest vascular access route performed by advanced life support (ALS)-trained paramedics was IV or humeral-IO. We fit a propensity-score adjusted model with inverse probability treatment weighting to estimate the association between IV vs. humeral-IO routes and favorable neurological outcomes (CPC 1-2) and survival at hospital discharge. We repeated models within subgroups defined by initial cardiac rhythm.

RESULTS: We included 2,112 cases; the first-attempted route was IV (n = 1,575) or humeral-IO (n = 537). Time intervals from ALS-paramedic on-scene arrival to vascular access (6.6 vs. 6.9 min) and epinephrine administration (9.0 vs. 9.3 min) were similar between IV and IO groups, respectively. Among IV and humeral-IO groups, 98 (6.2%) and 20 (3.7%) had favorable neurological outcomes. Compared to humeral-IO, an IV-first approach was associated with improved hospital-discharge favorable neurological outcomes (AOR 1.7; 95% CI 1.1-2.7) and survival (AOR 1.5; 95% CI 1.0-2.3). Among shockable rhythm cases, an IV-first approach was associated with improved favorable neurological outcomes (AOR 4.2; 95% CI 2.1-8.2), but not among non-shockable rhythm cases (AOR 0.73; 95% CI 0.39-1.4).

CONCLUSION: An IV-first approach, compared to humeral-IO, for intra-arrest resuscitation was associated with an improved odds of favorable neurological outcomes and survival to hospital discharge. This association was seen among an initial shockable rhythm, but not non-shockable rhythm, subgroups.}, } @article {pmid39154745, year = {2024}, author = {Vu, D and Park, M and Alhusayen, R}, title = {Response to Chawla et al, "Response to Vu et al's "Efficacy of moxifloxacin as a mono-antibiotic therapy for hidradenitis suppurativa: A retrospective cohort study"".}, journal = {Journal of the American Academy of Dermatology}, volume = {91}, number = {6}, pages = {e177-e178}, doi = {10.1016/j.jaad.2024.08.013}, pmid = {39154745}, issn = {1097-6787}, } @article {pmid39154744, year = {2024}, author = {Li, JN and Sechi, A and Tosti, A}, title = {Response to Costa Fechine et al's "Correlation of clinical and trichoscopy features with the degree of histologic inflammation in lichen planopilaris and frontal fibrosing alopecia in a cross-sectional study".}, journal = {Journal of the American Academy of Dermatology}, volume = {91}, number = {6}, pages = {e187-e188}, doi = {10.1016/j.jaad.2024.07.1495}, pmid = {39154744}, issn = {1097-6787}, } @article {pmid39153378, year = {2024}, author = {Maramai, S and Saletti, M and Paolino, M and Giuliani, G and Cazzola, J and Spaiardi, P and Talpo, F and Frosini, M and Pifferi, A and Ballarotto, M and Carotti, A and Poggialini, F and Vagaggini, C and Dreassi, E and Giorgi, G and Dondio, G and Cappelli, A and Rosario Biella, G and Anzini, M}, title = {Novel multitarget directed ligands inspired by riluzole: A serendipitous synthesis of substituted benzo[b][1,4]thiazepines potentially useful as neuroprotective agents.}, journal = {Bioorganic & medicinal chemistry}, volume = {112}, number = {}, pages = {117872}, doi = {10.1016/j.bmc.2024.117872}, pmid = {39153378}, issn = {1464-3391}, mesh = {Animals ; Humans ; Dose-Response Relationship, Drug ; Ligands ; Molecular Structure ; *Neuroprotective Agents/pharmacology/chemical synthesis/chemistry ; *Riluzole/pharmacology/chemical synthesis/chemistry ; Structure-Activity Relationship ; Thiazepines/chemical synthesis/chemistry/pharmacology ; }, abstract = {Riluzole, the first clinically approved treatment for amyotrophic lateral sclerosis (ALS), represents a successful example of a drug endowed with a multimodal mechanism of action. In recent years, different series of riluzole-based compounds have been reported, including several agents acting as Multi-Target-Directed Ligands (MTLDs) endowed with neuroprotective effects. Aiming at identical twin structures inspired by riluzole (2a-c), a synthetic procedure was planned, but the reactivity of the system took a different path, leading to the serendipitous isolation of benzo[b][1,4]thiazepines 3a-c and expanded intermediates N-cyano-benzo[b][1,4]thiazepines 4a-c, which were fully characterized. The newly obtained structures 3a-c, bearing riluzole key elements, were initially tested in an in vitro ischemia/reperfusion injury protocol, simulating the cerebral stroke. Results identified compound 3b as the most effective in reverting the injury caused by an ischemia-like condition, and its activity was comparable, or even higher than that of riluzole, exhibiting a concentration-dependent neuroprotective effect. Moreover, derivative 3b completely reverted the release of Lactate Dehydrogenase (LDH), lowering the values to those of the control slices. Based on its very promising pharmacological properties, compound 3b was then selected to assess its effects on voltage-dependent Na[+] and K[+] currents. The results indicated that derivative 3b induced a multifaceted inhibitory effect on voltage-gated currents in SH-SY5Y differentiated neurons, suggesting its possible applications in epilepsy and stroke management, other than ALS. Accordingly, brain penetration was also measured for 3b, as it represents an elegant example of a MTDL and opens the way to further ex-vivo and/or in-vivo characterization.}, } @article {pmid39153346, year = {2025}, author = {Khazaei, K and Roshandel, P and Parastar, H}, title = {Visible-short wavelength near infrared hyperspectral imaging coupled with multivariate curve resolution-alternating least squares for diagnosis of breast cancer.}, journal = {Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy}, volume = {324}, number = {}, pages = {124966}, doi = {10.1016/j.saa.2024.124966}, pmid = {39153346}, issn = {1873-3557}, mesh = {Humans ; Female ; *Breast Neoplasms/diagnosis ; Least-Squares Analysis ; *Principal Component Analysis ; *Spectroscopy, Near-Infrared/methods ; *Hyperspectral Imaging/methods ; Multivariate Analysis ; Discriminant Analysis ; }, abstract = {This study investigates the application of visible-short wavelength near-infrared hyperspectral imaging (Vis-SWNIR HSI) in the wavelength range of 400-950 nm and advanced chemometric techniques for diagnosing breast cancer (BC). The research involved 56 ex-vivo samples encompassing both cancerous and non-cancerous breast tissue from females. First, HSI images were analyzed using multivariate curve resolution-alternating least squares (MCR-ALS) to exploit pure spatial and spectral profiles of active components. Then, the MCR-ALS resolved spatial profiles were arranged in a new data matrix for exploration and discrimination between benign and cancerous tissue samples using principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA). The PLS-DA classification accuracy of 82.1 % showed the potential of HSI and chemometrics for non-invasive detection of BC. Additionally, the resolved spectral profiles by MCR-ALS can be used to track the changes in the breast tissue during cancer and treatment. It is concluded that the proposed strategy in this work can effectively differentiate between cancerous and non-cancerous breast tissue and pave the way for further studies and potential clinical implementation of this innovative approach, offering a promising avenue for improving early detection and treatment outcomes in BC patients.}, } @article {pmid39153108, year = {2024}, author = {Hosseini, L and Babaie, S and Shahabi, P and Fekri, K and Shafiee-Kandjani, AR and Mafikandi, V and Maghsoumi-Norouzabad, L and Abolhasanpour, N}, title = {Klotho: molecular mechanisms and emerging therapeutics in central nervous system diseases.}, journal = {Molecular biology reports}, volume = {51}, number = {1}, pages = {913}, pmid = {39153108}, issn = {1573-4978}, mesh = {*Klotho Proteins ; Humans ; *Central Nervous System Diseases/metabolism/drug therapy ; *Signal Transduction ; Animals ; Oxidative Stress ; Glucuronidase/metabolism/genetics ; Autophagy ; Aging/metabolism/genetics ; }, abstract = {Klotho is recognized as an aging-suppressor protein that is implicated in a variety of processes and signaling pathways. The anti-inflammatory, anti-apoptotic, anti-oxidant, and anti-tumor bioactivities of klotho have extended its application in neurosciences and made the protein popular for its lifespan-extending capacity. Furthermore, it has been demonstrated that klotho levels would reduce with aging and numerous pathologies, particularly those related to the central nervous system (CNS). Evidence supports the idea that klotho can be a key therapeutic target in CNS diseases such as amyotrophic lateral sclerosis, Parkinson's disease, stroke, and Alzheimer's disease. Reviewing the literature suggests that the upregulation of klotho expression regulates various signaling pathways related to autophagy, oxidative stress, inflammation, cognition, and ferroptosis in neurological disorders. Therefore, it has been of great interest to develop drugs or agents that boost or restore klotho levels. In this regard, the present review was designed and aimed to gather the delegated documents regarding the therapeutic potential of Klotho in CNS diseases focusing on the molecular and cellular mechanisms.}, } @article {pmid39152573, year = {2024}, author = {Dubbioso, R and Iannotti, FA and Senerchia, G and Verde, R and Iuzzolino, VV and Spisto, M and Fasolino, I and Manganelli, F and Di Marzo, V and Piscitelli, F}, title = {Circulating endocannabinoidome signatures of disease activity in amyotrophic lateral sclerosis.}, journal = {European journal of neurology}, volume = {31}, number = {10}, pages = {e16400}, pmid = {39152573}, issn = {1468-1331}, support = {E53D23019760001//National Recovery and Resilience Plan (NRRP)/ ; E53D23011330006//Ministry of University and Research (MUR)/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/blood ; *Endocannabinoids/blood ; Male ; Female ; Middle Aged ; Aged ; Adult ; Disease Progression ; Longitudinal Studies ; Biomarkers/blood ; }, abstract = {BACKGROUND AND PURPOSE: Preclinical studies of amyotrophic lateral sclerosis (ALS) have shown altered endocannabinoid (eCB) signalling that may contribute to the disease. Results from human studies are sparse and inconclusive. The aim of this study was to determine the association between serum levels of eCBs or their congeners, the so-called endocannabinoidome, and disease status and activity in ALS patients.

METHODS: Serum concentrations of 2-arachidonoylglycerol and N-arachidonoylethanolamine (AEA), and AEA congeners palmitoylethanolamide (PEA), oleoylethanolamide (OEA), eicosapentaenoylethanolamide (EPEA), 2-docosahexaenoylglycerol (2-DHG) and docosahexaenoylethanolamide (DHEA) were measured in samples from 65 ALS patients, 32 healthy controls (HCs) and 16 neurological disease controls (NALS). A subset of 46 ALS patients underwent a longitudinal study. Disease activity and progression were correlated with eCB and congener levels.

RESULTS: Most circulating mediators were higher in ALS than HCs (all p < 0.001), but not NALS. Across clinical stages, ALS patients showed increased levels of PEA, OEA and EPEA (all p < 0.02), which were confirmed by the longitudinal study (all p < 0.03). Serum PEA and OEA levels were independent predictors of survival and OEA levels were higher in patients complaining of appetite loss. Cluster analysis revealed two distinct profiles of circulating mediators associated with corresponding patterns of disease activity (severe vs. mild). Patients belonging to the 'severe' cluster showed significantly higher levels of OEA and PEA and lower levels of 2-DHG compared to NALS and HCs.

CONCLUSION: Circulating endocannabinoidome profiles are indicative of disease activity, thus possibly paving the way to a personalized, rather than a 'one-fits-all', therapeutic approach targeting the endocannabinoidome.}, } @article {pmid39150867, year = {2025}, author = {Pienaar, K and Kelaita, P and Murphy, D}, title = {COVID-19 and the biopolitics of stigma in public housing: dividing practices and community boundaries in pandemic times.}, journal = {Health sociology review : the journal of the Health Section of the Australian Sociological Association}, volume = {34}, number = {2}, pages = {167-182}, doi = {10.1080/14461242.2024.2390019}, pmid = {39150867}, issn = {1446-1242}, mesh = {Humans ; *COVID-19/epidemiology/psychology/prevention & control ; *Social Stigma ; *Public Housing ; SARS-CoV-2 ; Interviews as Topic ; Australia/epidemiology ; Pandemics ; Female ; Male ; Politics ; }, abstract = {The COVID-19 'hard lockdowns' in Melbourne, Australia in 2020 targeted public housing estates thus trading on perceptions of risk associated with public housing as some of the most stigmatised sites in post-industrial cities. This article draws on interviews with Melbourne public housing tenants on their experience of COVID-19 lockdowns to analyse the place of stigma in residents' accounts. Pairing Wacquant et al's (2014) concept of 'territorial stigma' with sociological work on the biopolitics of stigma we consider the dynamics of stigma, tracing how it functions to delimit community boundaries and justify pandemic containment measures. Residents navigate multiple layers of stigma, including stereotypes of public housing, normative judgements of neighbouring residents, and a broader public housing system riven with structural issues. Members of these communities are both the targets of stigma and seek to distance themselves from those seen as vectors of stigma. Our participants report mobilising social distancing strategies couched in normative assessments of perceived risk based on physical appearance, presumed drug use and past conduct. We explore the implications of these enactments of territorial stigma and trace the logics of abjection that construct public housing as deprived urban zones, home to abject 'Others' perceived as threatening the health of the community.}, } @article {pmid39149866, year = {2024}, author = {Cabeza-Fernández, S and Hernández-Rojas, R and Casillas-Bajo, A and Patel, N and de la Fuente, AG and Cabedo, H and Gomez-Sanchez, JA}, title = {Schwann cell JUN expression worsens motor performance in an amyotrophic lateral sclerosis mouse model.}, journal = {Glia}, volume = {72}, number = {12}, pages = {2178-2189}, doi = {10.1002/glia.24604}, pmid = {39149866}, issn = {1098-1136}, support = {PID2019-109762RB-I00//Agencia Estatal de Investigación/ ; PID2022-141062OB-I00//Agencia Estatal de Investigación/ ; CIPROM/2021/048//Conselleria d'Educació, Investigació, Cultura i Esport/ ; GRISOLIAP/2021/026//Conselleria d'Educació, Investigació, Cultura i Esport/ ; }, mesh = {Animals ; *Schwann Cells/metabolism/pathology ; *Amyotrophic Lateral Sclerosis/pathology/genetics/metabolism/physiopathology ; *Mice, Transgenic ; *Disease Models, Animal ; *Motor Neurons/pathology/metabolism ; Proto-Oncogene Proteins c-jun/metabolism/genetics ; Mice ; Spinal Cord/metabolism/pathology ; Superoxide Dismutase/genetics/metabolism ; Axons/pathology/metabolism/physiology ; Mice, Inbred C57BL ; }, abstract = {Amyotrophic lateral sclerosis is a devastating neurodegenerative disease characterized by motor neuron death and distal axonopathy. Despite its clinical severity and profound impact in the patients and their families, many questions about its pathogenesis remain still unclear, including the role of Schwann cells and axon-glial signaling in disease progression. Upon axonal injury, upregulation of JUN transcription factor promotes Schwann cell reprogramming into a repair phenotype that favors axon regrowth and neuronal survival. To study the potential role of repair Schwann cells on motoneuron survival in amyotrophic lateral sclerosis, we generated a mouse line that over-expresses JUN in the Schwann cells of the SOD1[G93A] mutant, a mouse model of this disease. Then, we explored disease progression by evaluating survival, motor performance and histology of peripheral nerves and spinal cord of these mice. We found that Schwann cell JUN overexpression does not prevent axon degeneration neither motor neuron death in the SOD1[G93A] mice. Instead, it induces a partial demyelination of medium and large size axons, worsening motor performance and resulting in more aggressive disease phenotype.}, } @article {pmid39147172, year = {2024}, author = {Acton, S and O'Donnell, MM and Periyasamy, K and Dixit, B and Eishingdrelo, H and Hill, C and Paul Ross, R and Chesnel, L}, title = {LPA3 agonist-producing Bacillus velezensis ADS024 is efficacious in multiple neuroinflammatory disease models.}, journal = {Brain, behavior, and immunity}, volume = {121}, number = {}, pages = {384-402}, doi = {10.1016/j.bbi.2024.08.024}, pmid = {39147172}, issn = {1090-2139}, mesh = {*Bacillus/metabolism ; Animals ; Mice ; Humans ; *Neuroinflammatory Diseases/metabolism ; Disease Models, Animal ; Mice, Inbred C57BL ; Multiple Sclerosis/metabolism ; Male ; Encephalomyelitis, Autoimmune, Experimental/metabolism ; Anti-Inflammatory Agents/pharmacology ; }, abstract = {Neuroinflammation is a common component of neurological disorders. In the gut-brain-immune axis, bacteria and their metabolites are now thought to play a role in the modulation of the nervous and immune systems which may impact neuroinflammation. In this respect, commensal bacteria of humans have recently been shown to produce metabolites that mimic endogenous G-protein coupled receptor (GPCR) ligands. To date, it has not been established whether plant commensal bacteria, which may be ingested by animals including humans, can impact the gut-brain-immune axis via GPCR agonism. We screened an isopropanol (IPA) extract of the plant commensal Bacillus velezensis ADS024, a non-engrafting live biotherapeutic product (LBP) with anti-inflammatory properties isolated from human feces, against a panel of 168 GPCRs and identified strong agonism of the lysophosphatidic acid (LPA) receptor LPA3. The ADS024 IPA extracted material (ADS024-IPA) did not agonize LPA2, and only very weakly agonized LPA1. The agonism of LPA3 was inhibited by the reversible LPA1/3 antagonist Ki16425. ADS024-IPA signaled downstream of LPA3 through G-protein-induced calcium release, recruitment of β-arrestin, and recruitment of the neurodegeneration-associated proteins 14-3-3γ, ε and ζ but did not recruit the β isoform. Since LPA3 agonism was previously indirectly implicated in the reduction of pathology in models of Parkinson's disease (PD) and multiple sclerosis (MS) by use of the nonselective antagonist Ki16425, and since we identified an LPA3-specific agonist within ADS024, we sought to examine whether LPA3 might indeed be part of a broad underlying mechanism to control neuroinflammation. We tested oral treatment of ADS024 in multiple models of neuroinflammatory diseases using three models of PD, two models of MS, and a model each of amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), and chemo-induced peripheral neuropathy (CIPN). ADS024 treatment improved model-specific functional effects including improvements in motor movement, breathing and swallowing, and allodynia suggesting that ADS024 treatment impacted a universal underlying neuroinflammatory mechanism regardless of the initiating cause of disease. We used the MOG-EAE mouse model to examine early events after disease initiation and found that ADS024 attenuated the increase in circulating lymphocytes and changes in neutrophil subtypes, and ADS024 attenuated the early loss of cell-surface LPA3 receptor expression on circulating white blood cells. ADS024 efficacy was partially inhibited by Ki16425 in vivo suggesting LPA3 may be part of its mechanism. Altogether, these data suggest that ADS024 and its LPA3 agonism activity should be investigated further as a possible treatment for diseases with a neuroinflammatory component.}, } @article {pmid39146882, year = {2024}, author = {Aizawa, H and Nagumo, S and Hideyama, T and Kato, H and Kwak, S and Terashi, H and Suzuki, Y and Kimura, T}, title = {Morphometric analysis of spinal motor neuron degeneration in sporadic amyotrophic lateral sclerosis.}, journal = {Journal of the neurological sciences}, volume = {464}, number = {}, pages = {123177}, doi = {10.1016/j.jns.2024.123177}, pmid = {39146882}, issn = {1878-5883}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/pathology/metabolism ; Male ; Female ; Middle Aged ; Aged ; *DNA-Binding Proteins/metabolism ; *Spinal Cord/pathology/metabolism ; *Nerve Degeneration/pathology ; Anterior Horn Cells/pathology ; Motor Neurons/pathology/metabolism ; }, abstract = {OBJECTIVES: This study aimed to clarify the relationship between 43-kDa TAR DNA-binding protein (TDP-43) pathology and spinal cord anterior horn motor neuron (AHMN) atrophy in sporadic amyotrophic lateral sclerosis (SALS).

METHODS: Eight patients with SALS and 12 controls were included in this study. Formalin-fixed specimens of lumbar spinal cord samples were paraffin-embedded and sectioned at the level of the fourth lumbar spinal cord with a 4 μm thickness. Using a microscope, the long diameters of the neurons with nucleoli were measured in spinal AHMNs stained with an anti-SMI-32 antibody. AHMNs were divided into medial and lateral nuclei for statistical analysis. We also used previously reported data to measure the long diameter of AHMNs with initial TDP-43 pathology, in which TDP-43 was present both in the nucleus and cytoplasm.

RESULTS: The long diameter of the lumbar spinal AHMNs in patients with SALS was smaller in the medial nucleus (42.54 ± 9.33 μm, n = 24) and the lateral nucleus (49.41 ± 13.86 μm, n = 129) than in controls (medial nucleus: 55.84 ± 13.49 μm, n = 85, p < 0.001; lateral nucleus: 62.39 ± 13.29 μm, n = 756, p < 0.001, Mann-Whitney U test). All 21 motor neurons with initial TDP-43 pathology were in the lateral nucleus, and their long diameter (67.60 ± 18.3 μm, p = 0.352) was not significantly different from that of controls.

CONCLUSION: Motor neuron atrophy in SALS does not occur during the initial stages of TDP-43 pathology, and TDP-43 pathology is already advanced in the atrophied motor neurons.}, } @article {pmid39146816, year = {2025}, author = {Sun, Q and Chai, L and Yang, X and Zhang, W and Li, Z}, title = {Hollow tubular sea-urchin structure with high catalytic activity of NiCo2Se4@CS2 cathodes for high-performance Al/S batteries.}, journal = {Journal of colloid and interface science}, volume = {677}, number = {Pt B}, pages = {284-292}, doi = {10.1016/j.jcis.2024.08.071}, pmid = {39146816}, issn = {1095-7103}, abstract = {The shuttle effect of aluminum polysulfides (AlPSs) have been a source of concern for studying Al/S batteries. Due to the weak adsorption of CS composites, research on cathode materials for Al/S batteries has been delayed. As it is generally known that Al2S3 decomposition demands a large Gibbs free energy, this work has tried to reduce the Al2S3 decomposition potential energy. Herein, the Ni/Co bimetallic selenide reduces the energy barrier conversion and mitigates the polarization effects, while morphology control enables the storage and anchoring of S, alleviating the shuttle effect. Additionally, the intermediate products serve as single-atom catalysts, increasing the active sites, synergistically enhancing the ion diffusion kinetics. DFT calculations verify that NiCo2Se4 has a moderate Gibbs free energy change during the rate-limiting step of S reduction and the most robust adsorption energy to Al2S3. NiCo2Se4@CS2/Al has a remaining capacity of 135 mAh/g after 450 cycles (at 200 mA g[-1]), pioneering novel ideas for the development of Al/S batteries.}, } @article {pmid39146722, year = {2024}, author = {Ginanneschi, F and Pucci, B and Casali, S and Lissandri, C and Giannini, F and Rossi, A}, title = {Factors associated with Edinburgh Cognitive and Behavioural ALS Screen (ECAS) alteration at time of diagnosis, in amyotrophic lateral sclerosis.}, journal = {Clinical neurology and neurosurgery}, volume = {245}, number = {}, pages = {108499}, doi = {10.1016/j.clineuro.2024.108499}, pmid = {39146722}, issn = {1872-6968}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/diagnosis ; Male ; Female ; Middle Aged ; Aged ; C9orf72 Protein/genetics ; Neuropsychological Tests ; Adult ; Mutation ; Cohort Studies ; }, abstract = {BACKGROUND: Edinburgh Cognitive and Behavioral ALS Screen (ECAS) is a validated assessment designed to screen cognitive functions and behavioral disorders in amyotrophic lateral sclerosis (ALS). Objective of this study is to determine the factors associated with ECAS impairment in a cohort of ALS patients without a co-morbid diagnosis of dementia, at the time of diagnosis.

METHODS: We enrolled 71 non-demented ALS patient. We collected clinical and demographic data, ALS familiarity, analysis of the most commonly mutated genes in ALS, ALS Milano Torino Staging System and ALS Functional Rate Scale revised scores, progression rate; finally, we recorded whether symptoms onset involved spinal or bulbar area. The alteration of the ECAS was estimated based on age and education-adjusted-validated cut off for each of the items included in ECAS. A multivariable regression analysis was done.

RESULTS: The significant determinants of ECAS alterations were: bulbar onset in both ALS-specific test and total ECAS score; bulbar onset and familiarity in ALS-non-specific test; finally, familiarity and diagnosis delay in ALS-behavioral test. All the subjects carrying C9orf72 mutations had alteration of both total ECAS score and ALS-specific tests.

DISCUSSION: At diagnosis, bulbar-onset ALS, family history, diagnosis delay and C9orf72 hexanucleotide repeat expansion may contribute to impairment of ECAS.}, } @article {pmid39146246, year = {2024}, author = {Hutten, S and Chen, JX and Isaacs, AM and Dormann, D}, title = {Poly-GR Impairs PRMT1-Mediated Arginine Methylation of Disease-Linked RNA-Binding Proteins by Acting as a Substrate Sink.}, journal = {Biochemistry}, volume = {63}, number = {17}, pages = {2141-2152}, doi = {10.1021/acs.biochem.4c00308}, pmid = {39146246}, issn = {1520-4995}, mesh = {*Protein-Arginine N-Methyltransferases/metabolism/genetics ; Humans ; *Arginine/metabolism ; Methylation ; *Repressor Proteins/metabolism/genetics ; *RNA-Binding Proteins/metabolism/genetics ; Amyotrophic Lateral Sclerosis/metabolism/genetics ; Frontotemporal Dementia/metabolism/genetics ; C9orf72 Protein/metabolism/genetics ; HEK293 Cells ; }, abstract = {Dipeptide repeat proteins (DPRs) are aberrant protein species found in C9orf72-linked amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), two neurodegenerative diseases characterized by the cytoplasmic mislocalization and aggregation of RNA-binding proteins (RBPs). In particular, arginine (R)-rich DPRs (poly-GR and poly-PR) have been suggested to promiscuously interact with multiple cellular proteins and thereby exert high cytotoxicity. Components of the protein arginine methylation machinery have been identified as modulators of DPR toxicity and/or potential cellular interactors of R-rich DPRs; however, the molecular details and consequences of such an interaction are currently not well understood. Here, we demonstrate that several members of the family of protein arginine methyltransferases (PRMTs) can directly interact with R-rich DPRs in vitro and in the cytosol. In vitro, R-rich DPRs reduce solubility and promote phase separation of PRMT1, the main enzyme responsible for asymmetric arginine-dimethylation (ADMA) in mammalian cells, in a concentration- and length-dependent manner. Moreover, we demonstrate that poly-GR interferes more efficiently than poly-PR with PRMT1-mediated arginine methylation of RBPs such as hnRNPA3. We additionally show by two alternative approaches that poly-GR itself is a substrate for PRMT1-mediated arginine dimethylation. We propose that poly-GR may act as a direct competitor for arginine methylation of cellular PRMT1 targets, such as disease-linked RBPs.}, } @article {pmid39145860, year = {2024}, author = {Gondo, TF and Huang, F and Marungruang, N and Heyman-Lindén, L and Turner, C}, title = {Investigating the quality of extraction and quantification of bioactive compounds in berries through liquid chromatography and multivariate curve resolution.}, journal = {Analytical and bioanalytical chemistry}, volume = {416}, number = {24}, pages = {5387-5400}, pmid = {39145860}, issn = {1618-2650}, support = {2018-01863//Svenska Forskningsrådet Formas/ ; }, mesh = {*Fruit/chemistry ; Multivariate Analysis ; Chromatography, Liquid/methods ; Polyphenols/analysis ; Least-Squares Analysis ; Plant Extracts/chemistry ; Anthocyanins/analysis/chemistry ; Phenols/analysis/chemistry ; Chromatography, High Pressure Liquid/methods ; Antioxidants/analysis/chemistry ; }, abstract = {Berries are a rich source of natural antioxidant compounds, which are essential to profile, as they add to their nutritional value. However, the complexity of the matrix and the structural diversity of these compounds pose challenges in extraction and chromatographic separation. By relying on multivariate curve resolution alternating least squares (MCR-ALS) ability to extract components from complex spectral mixtures, our study evaluates the contributions of various extraction techniques to interference, extractability, and quantifying different groups of overlapping compounds using liquid chromatography diode array detection (LC-DAD) data. Additionally, the combination of these methods extends its applicability to evaluate polyphenol degradation in stored berry smoothies, where evolving factor analysis (EFA) is also used to elucidate degradation products. Results indicate that among the extraction techniques, ultrasonication-assisted extraction employing 1% formic acid in methanol demonstrated superior extractability and selectivity for the different phenolic compound groups, compared with both pressurized liquid extraction and centrifugation of the fresh berry smoothie. Employing MCR-ALS on the LC-DAD data enabled reliable estimation of total amounts of compound classes with high spectral overlaps. Degradation studies revealed significant temperature-dependent effects on anthocyanins, with at least 50% degradation after 7 months of storage at room temperature, while refrigeration and freezing maintained fair stability for at least 12 months. The EFA model estimated phenolic derivatives as the main possible degradation products. These findings enhance the reliability of quantifying polyphenolic compounds and understanding their stability during the storage of berry products.}, } @article {pmid39145609, year = {2024}, author = {Adil, O and Adeyeye, C and Shamsi, MH}, title = {Electrografted Laser-Induced Graphene: Direct Detection of Neurodegenerative Disease Biomarker in Cerebrospinal Fluid.}, journal = {ACS sensors}, volume = {9}, number = {9}, pages = {4748-4757}, doi = {10.1021/acssensors.4c01150}, pmid = {39145609}, issn = {2379-3694}, support = {R15 GM147885/GM/NIGMS NIH HHS/United States ; }, mesh = {*Graphite/chemistry ; Humans ; *Biomarkers/cerebrospinal fluid ; *Electrochemical Techniques/methods ; *Lasers ; Immunoassay/methods ; Amyotrophic Lateral Sclerosis/cerebrospinal fluid/diagnosis ; Electrodes ; Neurodegenerative Diseases/cerebrospinal fluid/diagnosis ; Limit of Detection ; Biosensing Techniques/methods ; }, abstract = {There are more than 50 neurodegenerative disorders, and amyotrophic lateral sclerosis (ALS) is one of the most common disorders that poses diagnostic and treatment challenges. The poly glycine-proline (polyGP) dipeptide repeat is a toxic protein that has been recognized as a pharmacodynamic biomarker of C9orf72-associated (c9+) ALS, a subtype of ALS that originates from genetic mutation. Early detection of polyGP will help healthcare providers start timely gene therapy. Herein, we developed a label-free electrochemical immunoassay for the simple detection of polyGP in unprocessed cerebrospinal fluid (CSF) samples collected from ALS patients in the National ALS Biorepository. For the first time, an electrografted laser-induced graphene (E-LIG) electrode system was employed in a sandwich format to detect polyGP using a label-free electrochemical impedance technique. The results show that the E-LIG-modified surface exhibited high sensitivity and selectivity in buffer and CSF media with limit of detection values of 0.19 and 0.27 ng/mL, respectively. The precision of the calibration model was better in CSF than in the buffer. The E-LIG immunosensor can easily select polyGP targets in the presence of other dipeptide proteins translated from the c9 gene. Further study with CSF samples from ALS patients demonstrated that the label-free E-LIG-based immunosensor not only quantified polyGP in the complex CSF matrix but also distinguished between c9+ and non-c9- ALS patients.}, } @article {pmid39144751, year = {2024}, author = {Szebényi, K and Vargová, I and Petrova, V and Turečková, J and Gibbons, GM and Řehořová, M and Abdelgawad, M and Sándor, A and Marekova, D and Kwok, JCF and Jendelová, P and Fawcett, JW and Lakatos, A}, title = {Inhibition of PHLDA3 expression in human superoxide dismutase 1-mutant amyotrophic lateral sclerosis astrocytes protects against neurotoxicity.}, journal = {Brain communications}, volume = {6}, number = {4}, pages = {fcae244}, pmid = {39144751}, issn = {2632-1297}, abstract = {Pleckstrin homology-like domain family A-member 3 (PHLDA3) has recently been identified as a player in adaptive and maladaptive cellular stress pathways. The outcome of pleckstrin homology-like domain family A-member 3 signalling was shown to vary across different cell types and states. It emerges that its expression and protein level are highly increased in amyotrophic lateral sclerosis (ALS) patient-derived astrocytes. Whether it orchestrates a supportive or detrimental function remains unexplored in the context of neurodegenerative pathologies. To directly address the role of pleckstrin homology-like domain family A-member 3 in healthy and ALS astrocytes, we used overexpression and knockdown strategies. We generated cultures of primary mouse astrocytes and also human astrocytes from control and ALS patient-derived induced pluripotent stem cells harbouring the superoxide dismutase 1 mutation. Then, we assessed astrocyte viability and the impact of their secretome on oxidative stress responses in human stem cell-derived cortical and spinal neuronal cultures. Here, we show that PHLDA3 overexpression or knockdown in control astrocytes does not significantly affect astrocyte viability or reactive oxygen species production. However, PHLDA3 knockdown in ALS astrocytes diminishes reactive oxygen species concentrations in their supernatants, indicating that pleckstrin homology-like domain family A-member 3 can facilitate stress responses in cells with altered homeostasis. In support, supernatants of PHLDA3-silenced ALS and even control spinal astrocytes with a lower pleckstrin homology-like domain family A-member 3 protein content could prevent sodium arsenite-induced stress granule formation in spinal neurons. Our findings provide evidence that reducing pleckstrin homology-like domain family A-member 3 levels may transform astrocytes into a more neurosupportive state relevant to targeting non-cell autonomous ALS pathology.}, } @article {pmid39144569, year = {2024}, author = {Choudhury, C and Egleton, JE and Butcher, NJ and Russell, AJ and Minchin, RF}, title = {Small Molecule Inhibitors of Arylamine N-Acetyltransferase 1 Attenuate Cellular Respiration.}, journal = {ACS pharmacology & translational science}, volume = {7}, number = {8}, pages = {2326-2332}, pmid = {39144569}, issn = {2575-9108}, abstract = {Arylamine N-acetyltransferase 1 (NAT1) expression has been shown to attenuate mitochondrial function, suggesting it is a promising drug target in diseases of mitochondrial dysfunction. Here, several second-generation naphthoquinones have been investigated as small molecule inhibitors of NAT1. The results show that the compounds inhibit both in vitro and in whole cells. A lead compound (Cmp350) was further investigated for its ability to alter mitochondrial metabolism in MDA-MB-231 cells. At concentrations that inhibited NAT1 by over 85%, no overt toxicity was observed. Moreover, the inhibitor decreased basal respiration and reserve respiratory capacity without affecting ATP production. Cells treated with Cmp350 were almost exclusively dependent on glucose as a fuel source. We postulate that Cmp350 is an excellent lead compound for the development of NAT1-targeted inhibitors as both experimental tools and therapeutics in the treatment of hypermetabolic diseases such as amyotrophic lateral sclerosis, cancer cachexia, and sepsis.}, } @article {pmid39144302, year = {2024}, author = {Chen, XF and Lin, JP and Zhou, H and Kang, BZ and Nayak, R and Gao, L and Jiang, SS and Wang, F}, title = {The relationship between the collagen score at the anastomotic site of esophageal squamous cell carcinoma and anastomotic leakage.}, journal = {Journal of thoracic disease}, volume = {16}, number = {7}, pages = {4515-4524}, pmid = {39144302}, issn = {2072-1439}, abstract = {BACKGROUND: Anastomotic leakage (AL) has always been one of the most serious complications of esophagectomy with gastric conduit reconstruction. There are many strong risk factors for AL in clinical practice. Notably, the tension at the esophagogastric anastomosis and the blood supply to the gastric conduit directly affect the integrity of the anastomosis. However, there has been a lack of quantitative research on the tension and blood supply of the gastric conduit. Changes in extracellular matrix collagen reflect tension and blood supply, which affect the quality of the anastomosis. This study aimed to establish a quantitative collagen score to describe changes in the collagen structure in the extracellular matrix and to identify patients at high risk of postoperative AL.

METHODS: A retrospective study of 213 patients was conducted. Clinical and pathological data were collected at baseline. Optical imaging of the "donut" specimen at the anastomotic gastric end and collagen feature extraction were performed. Least absolute shrinkage and selection operator (LASSO) regression models were used to select the significant collagen features, compute collagen scores, and validate the predictive efficacy of the collagen scores for ALs.

RESULTS: LASSO regression analysis revealed three collagen-related parameters in the gastric donuts: histogram mean, histogram variance, and histogram energy. Based on this analysis, we established a formula to calculate the collagen score. The results of the univariate analysis revealed significant differences in the preoperative low albumin values (P=0.002) and collagen scores between the AL and non-AL groups (P=0.001), while the results of the multivariate analysis revealed significant differences in the collagen scores between the AL and non-AL groups (P=0.002). The areas under the curve (AUCs) of the experimental and validation cohorts were 0.978 [95% confidence interval (CI): 0.931-0.996] and 0.900 (95% CI: 0.824-0.951), respectively.

CONCLUSIONS: The collagen score established herein was shown to be related to AL and can be used to predict AL in patients who underwent esophagectomy.}, } @article {pmid39144033, year = {2024}, author = {Xiao, XY and Zeng, JY and Cao, YB and Tang, Y and Zou, ZY and Li, JQ and Chen, HJ}, title = {Cortical microstructural abnormalities in amyotrophic lateral sclerosis: a gray matter-based spatial statistics study.}, journal = {Quantitative imaging in medicine and surgery}, volume = {14}, number = {8}, pages = {5774-5788}, pmid = {39144033}, issn = {2223-4292}, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS)-related white-matter microstructural abnormalities have received considerable attention; however, gray-matter structural abnormalities have not been fully elucidated. This study aimed to evaluate cortical microstructural abnormalities in ALS and determine their association with disease severity.

METHODS: This study included 34 patients with ALS and 30 healthy controls. Diffusion-weighted data were used to estimate neurite orientation dispersion and density imaging (NODDI) parameters, including neurite density index (NDI) and orientation dispersion index (ODI). We performed gray matter-based spatial statistics (GBSS) in a voxel-wise manner to determine the cortical microstructure difference. We used the revised ALS Functional Rating Scale (ALSFRS-R) to assess disease severity and conducted a correlation analysis between NODDI parameters and ALSFRS-R.

RESULTS: In patients with ALS, the NDI reduction involved several cortical regions [primarily the precentral gyrus, postcentral gyrus, temporal cortex, prefrontal cortex, occipital cortex, and posterior parietal cortex; family-wise error (FWE)-corrected P<0.05]. ODI decreased in relatively few cortical regions (including the precentral gyrus, postcentral gyrus, prefrontal cortex, and inferior parietal lobule; FWE-corrected P<0.05). The NDI value in the left precentral and postcentral gyrus was positively correlated with the ALS disease severity (FWE-corrected P<0.05).

CONCLUSIONS: The decreases in NDI and ODI involved both motor-related and extra-motor regions and indicated the presence of gray-matter microstructural impairment in ALS. NODDI parameters are potential imaging biomarkers for evaluating disease severity in vivo. Our results showed that GBSS is a feasible method for identifying abnormalities in the cortical microstructure of patients with ALS.}, } @article {pmid39143255, year = {2024}, author = {Gehlen, M and Schwarz-Eywill, M and Mahn, K and Pfeiffer, A and Bauer, JM and Maier, A}, title = {[Sonography of muscles : Rheumatology-Neurology-Geriatrics-Sports medicine-Orthopedics].}, journal = {Zeitschrift fur Rheumatologie}, volume = {83}, number = {10}, pages = {829-843}, pmid = {39143255}, issn = {1435-1250}, mesh = {Humans ; *Ultrasonography/methods ; Magnetic Resonance Imaging ; Rheumatology/methods ; Muscle, Skeletal/diagnostic imaging ; Athletic Injuries/diagnostic imaging ; Sarcopenia/diagnostic imaging ; Sports Medicine/methods ; Rheumatic Diseases/diagnostic imaging ; Geriatrics ; Aged ; Neurology ; Muscular Diseases/diagnostic imaging ; Evidence-Based Medicine ; }, abstract = {Muscle sonography is used in rheumatology, neurology, geriatrics, sports medicine and orthopedics. Muscular atrophy with fatty and connective tissue degeneration can be visualized and must be interpreted in conjunction with the sonographic findings of the supplying nerves. Sonography is becoming increasingly more important for the early diagnosis of sarcopenia in rheumatology, geriatrics and osteology. Even if its significance has not yet been conclusively clarified, many publications confirm the high reliability of the method. Sonography can ideally be used in addition to magnetic resonance imaging (MRI) in the diagnostics of myositis as it can speed up the diagnosis, muscle groups that were not imaged by MRI can also be assessed sonographically and all muscle groups can be examined during the course of the procedure. Sonography also helps to make a quick and uncomplicated diagnosis of many sports injuries in addition to MRI and is therefore the basis for a targeted therapeutic approach.}, } @article {pmid39142444, year = {2024}, author = {Tan, X and Su, X and Wang, Y and Liang, W and Wang, D and Huo, D and Wang, H and Qi, Y and Zhang, W and Han, L and Zhang, D and Wang, M and Xu, J and Feng, H}, title = {RBM5 induces motor neuron apoptosis in hSOD1[G93A]-related amyotrophic lateral sclerosis by inhibiting Rac1/AKT pathways.}, journal = {Brain research bulletin}, volume = {216}, number = {}, pages = {111049}, doi = {10.1016/j.brainresbull.2024.111049}, pmid = {39142444}, issn = {1873-2747}, mesh = {*Amyotrophic Lateral Sclerosis/metabolism/genetics/pathology ; Animals ; *rac1 GTP-Binding Protein/metabolism/genetics ; *Motor Neurons/metabolism/pathology ; *Apoptosis/physiology ; *RNA-Binding Proteins/metabolism/genetics ; Mice ; Humans ; *Signal Transduction/physiology ; *Proto-Oncogene Proteins c-akt/metabolism ; Mice, Transgenic ; Superoxide Dismutase/metabolism/genetics ; Male ; DNA-Binding Proteins ; Cell Cycle Proteins ; Tumor Suppressor Proteins ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder distinguished by gradual depletion of motor neurons. RNA binding motif protein 5 (RBM5), an abundantly expressed RNA-binding protein, plays a critical role in the process of cellular death. However, little is known about the role of RBM5 in the pathogenesis of ALS. Here, we found that RBM5 was upregulated in ALS hSOD1[G93A]-NSC34 cell models and hSOD1[G93A] mice due to a reduction of miR-141-5p. The upregulation of RBM5 increased the apoptosis of motor neurons by inhibiting Rac1-mediated neuroprotection. In contrast, genetic knockdown of RBM5 rescued motor neurons from hSOD1[G93A]-induced degeneration by activating Rac1 signaling. The neuroprotective effect of RBM5-knockdown was significantly inhibited by the Rac1 inhibitor, NSC23766. These findings suggest that RBM5 could potentially serve as a therapeutic target in ALS by activating the Rac1 signalling.}, } @article {pmid39141854, year = {2024}, author = {Vansteensel, MJ and Leinders, S and Branco, MP and Crone, NE and Denison, T and Freudenburg, ZV and Geukes, SH and Gosselaar, PH and Raemaekers, M and Schippers, A and Verberne, M and Aarnoutse, EJ and Ramsey, NF}, title = {Longevity of a Brain-Computer Interface for Amyotrophic Lateral Sclerosis.}, journal = {The New England journal of medicine}, volume = {391}, number = {7}, pages = {619-626}, pmid = {39141854}, issn = {1533-4406}, support = {INTENSE, 17619//Nederlandse Organisatie voor Wetenschappelijk Onderzoek/ ; UH3 NS114439/NS/NINDS NIH HHS/United States ; U01DC016686/DC/NIDCD NIH HHS/United States ; U01 DC016686/DC/NIDCD NIH HHS/United States ; UH3NS114439/NS/NINDS NIH HHS/United States ; UGT7685, Economic Affairs SSM06011 and STW 12803//Netherlands Institute of Government/ ; }, mesh = {Female ; Humans ; Middle Aged ; *Amyotrophic Lateral Sclerosis/complications/diagnostic imaging/rehabilitation ; *Atrophy/diagnostic imaging/etiology/prevention & control ; Brain/diagnostic imaging ; *Brain-Computer Interfaces ; Communication Devices for People with Disabilities ; Time Factors ; Treatment Failure ; Electrodes, Implanted ; }, abstract = {The durability of communication with the use of brain-computer interfaces in persons with progressive neurodegenerative disease has not been extensively examined. We report on 7 years of independent at-home use of an implanted brain-computer interface for communication by a person with advanced amyotrophic lateral sclerosis (ALS), the inception of which was reported in 2016. The frequency of at-home use increased over time to compensate for gradual loss of control of an eye-gaze-tracking device, followed by a progressive decrease in use starting 6 years after implantation. At-home use ended when control of the brain-computer interface became unreliable. No signs of technical malfunction were found. Instead, the amplitude of neural signals declined, and computed tomographic imaging revealed progressive atrophy, which suggested that ALS-related neurodegeneration ultimately rendered the brain-computer interface ineffective after years of successful use, although alternative explanations are plausible. (Funded by the National Institute on Deafness and Other Communication Disorders and others; ClinicalTrials.gov number, NCT02224469.).}, } @article {pmid39141853, year = {2024}, author = {Card, NS and Wairagkar, M and Iacobacci, C and Hou, X and Singer-Clark, T and Willett, FR and Kunz, EM and Fan, C and Vahdati Nia, M and Deo, DR and Srinivasan, A and Choi, EY and Glasser, MF and Hochberg, LR and Henderson, JM and Shahlaie, K and Stavisky, SD and Brandman, DM}, title = {An Accurate and Rapidly Calibrating Speech Neuroprosthesis.}, journal = {The New England journal of medicine}, volume = {391}, number = {7}, pages = {609-618}, pmid = {39141853}, issn = {1533-4406}, support = {U01DC17844/DC/NIDCD NIH HHS/United States ; AL220043//Congressionally Directed Medical Research Programs/ ; U01 DC019430/DC/NIDCD NIH HHS/United States ; R01 MH060974/MH/NIMH NIH HHS/United States ; 872146SPI//Simons Foundation/ ; A2295-R//U.S. Department of Veterans Affairs/ ; DP2DC021055/DC/NIDCD NIH HHS/United States ; U01DC019430/DC/NIDCD NIH HHS/United States ; I01 RX002295/RX/RRD VA/United States ; DP2 DC021055/DC/NIDCD NIH HHS/United States ; U01 DC017844/DC/NIDCD NIH HHS/United States ; }, mesh = {Humans ; Male ; Middle Aged ; *Amyotrophic Lateral Sclerosis/complications/rehabilitation ; *Brain-Computer Interfaces ; Calibration ; Communication Devices for People with Disabilities ; *Dysarthria/rehabilitation/etiology ; Electrodes, Implanted ; Microelectrodes ; Quadriplegia/etiology/rehabilitation ; *Speech ; }, abstract = {BACKGROUND: Brain-computer interfaces can enable communication for people with paralysis by transforming cortical activity associated with attempted speech into text on a computer screen. Communication with brain-computer interfaces has been restricted by extensive training requirements and limited accuracy.

METHODS: A 45-year-old man with amyotrophic lateral sclerosis (ALS) with tetraparesis and severe dysarthria underwent surgical implantation of four microelectrode arrays into his left ventral precentral gyrus 5 years after the onset of the illness; these arrays recorded neural activity from 256 intracortical electrodes. We report the results of decoding his cortical neural activity as he attempted to speak in both prompted and unstructured conversational contexts. Decoded words were displayed on a screen and then vocalized with the use of text-to-speech software designed to sound like his pre-ALS voice.

RESULTS: On the first day of use (25 days after surgery), the neuroprosthesis achieved 99.6% accuracy with a 50-word vocabulary. Calibration of the neuroprosthesis required 30 minutes of cortical recordings while the participant attempted to speak, followed by subsequent processing. On the second day, after 1.4 additional hours of system training, the neuroprosthesis achieved 90.2% accuracy using a 125,000-word vocabulary. With further training data, the neuroprosthesis sustained 97.5% accuracy over a period of 8.4 months after surgical implantation, and the participant used it to communicate in self-paced conversations at a rate of approximately 32 words per minute for more than 248 cumulative hours.

CONCLUSIONS: In a person with ALS and severe dysarthria, an intracortical speech neuroprosthesis reached a level of performance suitable to restore conversational communication after brief training. (Funded by the Office of the Assistant Secretary of Defense for Health Affairs and others; BrainGate2 ClinicalTrials.gov number, NCT00912041.).}, } @article {pmid39141064, year = {2024}, author = {Wiesenfarth, M and Forouhideh-Wiesenfarth, Y and Elmas, Z and Parlak, Ö and Weiland, U and Herrmann, C and Schuster, J and Freischmidt, A and Müller, K and Siebert, R and Günther, K and Fröhlich, E and Knehr, A and Simak, T and Bachhuber, F and Regensburger, M and Petri, S and Klopstock, T and Reilich, P and Schöberl, F and Schumann, P and Körtvélyessy, P and Meyer, T and Ruf, WP and Witzel, S and Tumani, H and Brenner, D and Dorst, J and Ludolph, AC}, title = {Clinical characterization of common pathogenic variants of SOD1-ALS in Germany.}, journal = {Journal of neurology}, volume = {271}, number = {10}, pages = {6667-6679}, pmid = {39141064}, issn = {1432-1459}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/diagnosis ; *Superoxide Dismutase-1/genetics ; Male ; Female ; Germany ; Middle Aged ; Aged ; *Disease Progression ; Mutation ; Adult ; Phenotype ; }, abstract = {Pathogenic variants in the Cu/Zn superoxide dismutase (SOD1) gene can be detected in approximately 2% of sporadic and 11% of familial amyotrophic lateral sclerosis (ALS) patients in Europe. We analyzed the clinical phenotypes of 83 SOD1-ALS patients focusing on patients carrying the most frequent (likely) pathogenic variants (R116G, D91A, L145F) in Germany. Moreover, we describe the effect of tofersen treatment on ten patients carrying these variants. R116G patients showed the most aggressive course of disease with a median survival of 22.0 months compared to 198.0 months in D91A and 87.0 months in L145F patients (HR 7.71, 95% CI 2.89-20.58 vs. D91A; p < 0.001 and HR 4.25, 95% CI 1.55-11.67 vs. L145F; p = 0.02). Moreover, R116G patients had the fastest median ALSFRS-R progression rate with 0.12 (IQR 0.07-0.20) points lost per month. Median diagnostic delay was 10.0 months (IQR 5.5-11.5) and therefore shorter compared to 57.5 months (IQR 14.0-83.0) in D91A (p < 0.001) and 21.5 months (IQR 5.8-38.8) in L145F (p = 0.21) carriers. As opposed to D91A carriers (50.0%), 96.2% of R116G (p < 0.001) and 100.0% of L145F (p = 0.04) patients reported a positive family history. During tofersen treatment, all patients showed a reduction of neurofilament light chain (NfL) serum levels, independent of the SOD1 variant. Patients with SOD1-ALS carrying R116G, D91A, or L145F variants show commonalities, but also differences in their clinical phenotype, including a faster progression rate with shorter survival in R116G, and a comparatively benign disease course in D91A carriers.}, } @article {pmid39140323, year = {2024}, author = {Nakamura, T and He, X and Hattori, N and Hida, E and Hirata, M}, title = {Dilemma in patients with amyotrophic lateral sclerosis and expectations from brain-machine interfaces.}, journal = {Annals of medicine}, volume = {56}, number = {1}, pages = {2386516}, pmid = {39140323}, issn = {1365-2060}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/psychology/therapy ; *Brain-Computer Interfaces ; Male ; Female ; Middle Aged ; Aged ; Surveys and Questionnaires ; *Motivation ; *Caregivers/psychology ; *Anxiety/psychology/etiology ; Adult ; Tracheostomy ; Caregiver Burden/psychology ; Locked-In Syndrome/psychology ; }, abstract = {OBJECTIVE: We hypothesized that patients with amyotrophic lateral sclerosis (ALS) face a dilemma between motivation to live and difficulty in living, and brain-machine interfaces (BMIs) can reduce this dilemma. This study aimed to investigate the present situation of patients with ALS and their expectations from BMIs.

MATERIALS AND METHODS: Our survey design consisted of an anonymous mail-in questionnaire comprising questions regarding the use of tracheostomy positive pressure ventilation (TPPV), motivation to live, anxiety about the totally locked-in state (TLS), anxiety about caregiver burden, and expectations regarding the use of BMI. Primary outcomes were scores for motivation to live and anxiety about caregiver burden and the TLS. Outcomes were evaluated using the visual analogue scale.

RESULTS: Among 460 participants, 286 (62.6%) were already supported by or had decided to use TPPV. The median scores for motivation to live, anxiety about TLS, and anxiety about caregiver burden were 8.0, 9.0, and 7.0, respectively. Overall, 49% of patients intended to use BMI. Among patients who had refused TPPV, 15.9% intended to use BMI and TPPV. Significant factors for the use of BMI were motivation to live (p = .003), anxiety about TLS (p < .001), younger age (p < .001), and advanced disease stage (p < .001).

CONCLUSIONS: These results clearly revealed a serious dilemma among patients with ALS between motivation to live and their anxiety about TLS and caregiver burden. Patients expected BMI to reduce this dilemma. Thus, the development of better BMIs may meet these expectations.}, } @article {pmid39139642, year = {2024}, author = {Liu, X and Li, Y and Huang, L and Kuang, Y and Wu, X and Ma, X and Zhao, B and Lan, J}, title = {Unlocking the therapeutic potential of P2X7 receptor: a comprehensive review of its role in neurodegenerative disorders.}, journal = {Frontiers in pharmacology}, volume = {15}, number = {}, pages = {1450704}, pmid = {39139642}, issn = {1663-9812}, abstract = {The P2X7 receptor (P2X7R), an ATP-gated ion channel, has emerged as a crucial player in neuroinflammation and a promising therapeutic target for neurodegenerative disorders. This review explores the current understanding of P2X7R's structure, activation, and physiological roles, focusing on its expression and function in microglial cells. The article examines the receptor's involvement in calcium signaling, microglial activation, and polarization, as well as its role in the pathogenesis of Alzheimer's disease, Parkinson's disease, multiple sclerosis, and amyotrophic lateral sclerosis. The review highlights the complex nature of P2X7R signaling, discussing its potential neuroprotective and neurotoxic effects depending on the disease stage and context. It also addresses the development of P2X7R antagonists and their progress in clinical trials, identifying key research gaps and future perspectives for P2X7R-targeted therapy development. By providing a comprehensive overview of the current state of knowledge and future directions, this review serves as a valuable resource for researchers and clinicians interested in exploring the therapeutic potential of targeting P2X7R for the treatment of neurodegenerative disorders.}, } @article {pmid39139312, year = {2024}, author = {Kaur, B and Samagh, N and Narang, A and Paliwal, S}, title = {Anesthetic Management of a Neurosurgical Patient With Amyotrophic Lateral Sclerosis: A Case Report.}, journal = {Cureus}, volume = {16}, number = {7}, pages = {e64492}, pmid = {39139312}, issn = {2168-8184}, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive form of neurological disorder that affects both the upper and lower motor neurons. Anesthesia management in these patients is always challenging as they can develop respiratory complications because of pre-existing muscle involvement. We report a middle-aged male with ALS posted for chronic subdural hematoma evacuation (CSDH) surgery. Surgery was done under scalp block with monitored anesthesia care. The choice of anesthesia in these patients should be one that interferes the least with the disease pattern while still providing optimal conditions for surgery.}, } @article {pmid39138961, year = {2024}, author = {Rosano, A and Bicaj, M and Cillerai, M and Ponzano, M and Cabona, C and Gemelli, C and Caponnetto, C and Pardini, M and Signori, A and Uccelli, A and Schenone, A and Ferraro, PM}, title = {Psychological resilience is protective against cognitive deterioration in motor neuron diseases.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {25}, number = {7-8}, pages = {717-725}, doi = {10.1080/21678421.2024.2385690}, pmid = {39138961}, issn = {2167-9223}, mesh = {Humans ; Male ; Female ; Middle Aged ; *Resilience, Psychological ; *Motor Neuron Disease/psychology/complications ; Aged ; *Cognitive Dysfunction/psychology/etiology ; Neuropsychological Tests ; Longitudinal Studies ; Adult ; }, abstract = {OBJECTIVES: Recent studies suggest that psychological resilience (PR) is associated with more well-preserved cognition in healthy subjects (HS), but an investigation of such phenomenon in patients with motor neuron diseases (MNDs) is still lacking. The aim of our study was therefore to evaluate PR and its relationship with baseline cognitive/behavioral and mood symptoms, as well as longitudinal cognitive functioning, in MNDs.

METHODS: 94 MND patients and 87 demographically matched HS were enrolled. PR was assessed using the Connor-Davidson Resilience Scale (CD-RISC). Patients were further evaluated both at baseline and every 6 months for cognitive/behavioral disturbances using the Edinburgh Cognitive and Behavioral ALS Screen (ECAS), and for mood symptoms using the Hospital Anxiety and Depression Scale (HADS). CD-RISC scores were compared between patients and HS using the Mann-Whitney U test, and regression models were applied to evaluate the role of CD-RISC scores in predicting baseline cognitive/behavioral and mood measures, as well as longitudinal cognitive performances, in MND patients.

RESULTS: MND cases showed significantly greater PR compared to HS (p from <0.001 to 0.02). In MNDs, higher PR levels were significant predictors of both greater cognitive performance (p from 0.01 to 0.05) and milder mood symptoms (p from <0.001 to 0.04) at baseline, as well as less severe memory decline (p from 0.001 to 0.04) longitudinally.

CONCLUSIONS: PR is an important protective factor against the onset and evolution of cognitive/mood disturbances in MNDs, suggesting the usefulness of resilience enhancement psychological interventions to prevent or delay cognitive and mood disorders in these neurodegenerative conditions.}, } @article {pmid39138578, year = {2024}, author = {Wasielewska, JM and Chaves, JCS and Cabral-da-Silva, MC and Pecoraro, M and Viljoen, SJ and Nguyen, TH and Bella, V and Oikari, LE and Ooi, L and White, AR}, title = {A patient-derived amyotrophic lateral sclerosis blood-brain barrier model for focused ultrasound-mediated anti-TDP-43 antibody delivery.}, journal = {Fluids and barriers of the CNS}, volume = {21}, number = {1}, pages = {65}, pmid = {39138578}, issn = {2045-8118}, support = {PhD Scholarship//University of Queensland/ ; PhD Top-Up Scholarship//QIMR Berghofer Medical Research Institute/ ; APP1125796 and 1118452//National Health and Medical Research Council/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/metabolism/drug therapy ; *Blood-Brain Barrier/metabolism/drug effects ; Humans ; *Microbubbles ; *DNA-Binding Proteins/metabolism ; Drug Delivery Systems/methods ; Endothelial Cells/metabolism ; Antibodies/administration & dosage ; Ultrasonic Waves ; Cells, Cultured ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a rapidly progressing neurodegenerative disorder with minimally effective treatment options. An important hurdle in ALS drug development is the non-invasive therapeutic access to the motor cortex currently limited by the presence of the blood-brain barrier (BBB). Focused ultrasound and microbubble (FUS[+ MB]) treatment is an emerging technology that was successfully used in ALS patients to temporarily open the cortical BBB. However, FUS[+ MB]-mediated drug delivery across ALS patients' BBB has not yet been reported. Similarly, the effects of FUS[+ MB] on human ALS BBB cells remain unexplored.

METHODS: Here we established the first FUS[+ MB]-compatible, fully-human ALS patient-cell-derived BBB model based on induced brain endothelial-like cells (iBECs) to study anti-TDP-43 antibody delivery and FUS[+ MB] bioeffects in vitro.

RESULTS: Generated ALS iBECs recapitulated disease-specific hallmarks of BBB pathology, including reduced BBB integrity and permeability, and TDP-43 proteinopathy. The results also identified differences between sporadic ALS and familial (C9orf72 expansion carrying) ALS iBECs reflecting patient heterogeneity associated with disease subgroups. Studies in these models revealed successful ALS iBEC monolayer opening in vitro with no adverse cellular effects of FUS[+ MB] as reflected by lactate dehydrogenase (LDH) release viability assay and the lack of visible monolayer damage or morphology change in FUS[+ MB] treated cells. This was accompanied by the molecular bioeffects of FUS[+ MB] in ALS iBECs including changes in expression of tight and adherens junction markers, and drug transporter and inflammatory mediators, with sporadic and C9orf72 ALS iBECs generating transient specific responses. Additionally, we demonstrated an effective increase in the delivery of anti-TDP-43 antibody with FUS[+ MB] in C9orf72 (2.7-fold) and sporadic (1.9-fold) ALS iBECs providing the first proof-of-concept evidence that FUS[+ MB] can be used to enhance the permeability of large molecule therapeutics across the BBB in a human ALS in vitro model.

CONCLUSIONS: Together, this study describes the first characterisation of cellular and molecular responses of ALS iBECs to FUS[+ MB] and provides a fully-human platform for FUS[+ MB]-mediated drug delivery screening on an ALS BBB in vitro model.}, } @article {pmid39138120, year = {2025}, author = {Euler, L and Deinert, K and Wagener, F and Walpurgis, K and Thevis, M}, title = {Identification of human metabolites of fast skeletal troponin activators Tirasemtiv and Reldesemtiv for doping control purposes.}, journal = {Drug testing and analysis}, volume = {17}, number = {6}, pages = {812-824}, pmid = {39138120}, issn = {1942-7611}, support = {//Federal Ministry of Interior, Building and Community/ ; //Manfred-Donike-Institute for Doping Analysis/ ; }, mesh = {Humans ; *Doping in Sports/prevention & control ; *Substance Abuse Detection/methods ; Microsomes, Liver/metabolism ; Tandem Mass Spectrometry/methods ; Male ; Cell Line ; Pyridines ; Pyrimidines ; Pyrroles ; }, abstract = {The fast skeletal troponin activators (FSTAs) Reldesemtiv and Tirasemtiv were developed for patients suffering from neuro-degenerative diseases of the motor nervous system, e.g. amyotrophic lateral sclerosis (ALS). The drug candidates can increase the sensitivity of troponin C to calcium by selectively activating the troponin complex resulting in increased skeletal muscle contraction. Although the development of the drug candidates is currently discontinued because of missed end points in phase III clinical studies with patients with ALS, phase I clinical trials showed an increase in muscle contraction force in healthy humans. This effect could be abused by athletes to enhance performance in sports. As the substances are listed on the 2024 edition of the World Anti-Doping Agency's Prohibited List, the aim of this study was to identify and characterize metabolites of Reldesemtiv and Tirasemtiv to ensure their reliable identification in doping control analyses. The biotransformation of the drug candidates was studied in vitro using pooled human liver microsomes and 3D cultivated human hepatic cells of the cell line HepaRG, yielding a total of 11 metabolites of Reldesemtiv and eight of Tirasemtiv. In addition, a human elimination study was conducted to investigate the metabolism and elimination profile of Tirasemtiv and Reldesemtiv in vivo, suggesting the N-glucuronide of Tirasemtiv and hydroxylated 3-fluoro-2-(3-fluoro-1-methylcyclobutyl)pyridine as well as its glucuronide as suitable target analytes for routine doping controls. Applying a validating HPLC-MS/MS method, optimized to detect Reldesemtiv and Tirasemtiv in human urine, microdosing (50 μg) of each substance was traceable for 24-72 h.}, } @article {pmid39138039, year = {2024}, author = {Candelo, E and Vasudevan, SS and Orellana, D and Williams, AM and Rutt, AL}, title = {Exploring the Impact of Amyotrophic Lateral Sclerosis on Otolaryngological Functions.}, journal = {Journal of voice : official journal of the Voice Foundation}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jvoice.2024.07.025}, pmid = {39138039}, issn = {1873-4588}, abstract = {IMPORTANCE: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by progressive degeneration of upper and lower motor neurons at the spinal or bulbar level.

OBJECTIVE: We aim to describe the most frequent otolaryngology (ORL) complaints and voice disturbances in patients with bulbar onset ALS.

DESIGN: Retrospective cohort study.

SETTING: Single-center study with combined ORL and ALS clinic evaluation.

PARTICIPANTS: Patients with a confirmed diagnosis of ALS following an ORL visit and who underwent comprehensive voice assessments between January 2021 and January 2023.

EXPOSURE: Objective voice assessments.

MAIN OUTCOMES AND MEASURES: Glottal functional index (GFI), voice handicap index (VHI), reflux system index (RSI), and voice quality characteristics such as shimmer, jitter, maximum phonation time (MPT), and other essential parameters were assessed.

RESULTS: One hundred and thirty-three patients (age 62.17 ± 10.79, 54.48% female) were included. Three patients were referred from the ORL department to the ALS clinic. The most frequent symptoms were; dysphagia, dysarthria, facial weakness, pseudobulbar affect, and sialorrhea. The mean of forced vital capacity was 59.85%, EAT-10 15.91 ± 11.66, RSI 25.84 ± 9.03, GFI 14.12 ± 5.58, VHI-10 42.81 ± 34.94, MPT 15.22 s ± 8.06. Many patients reported voice impairments mainly related to spastic dysarthria and the combination of lower and upper motor neuron dysarthria, hypernasality, reduced verbal expression, and articulatory accuracy. Shimmer was increased to 8.46% ± 7.20, and jitter to 2.26% ± 1.39.

CONCLUSIONS AND RELEVANCE: Based on our cohort, this population with bulbar onset ALS has a higher frequency of voice disturbance characterized by hypernasality, spastic dysarthria, and reduced verbal expression.

LEVEL OF EVIDENCE: Level 3.}, } @article {pmid39137976, year = {2024}, author = {Pavey, N and Hannaford, A and Higashihara, M and van den Bos, M and Geevasinga, N and Vucic, S and Menon, P}, title = {Cortical inexcitability in ALS: correlating a clinical phenotype.}, journal = {Journal of neurology, neurosurgery, and psychiatry}, volume = {96}, number = {3}, pages = {}, pmid = {39137976}, issn = {1468-330X}, abstract = {BACKGROUND: Cortical inexcitability, a less studied feature of upper motor neuron (UMN) dysfunction in amyotrophic lateral sclerosis (ALS), was identified in a large cross-sectional cohort of ALS patients and their demographic and clinical characteristics were contrasted with normal or hyperexcitable ALS cohorts to assess the impact of cortical inexcitability on ALS phenotype and survival.

METHODS: Threshold-tracking transcranial magnetic stimulation (TMS) technique with measurement of mean short interval intracortical inhibition (SICI) differentiated ALS patients into three groups (1) inexcitable (no TMS response at maximal stimulator output in the setting of preserved lower motor neuron (LMN) function), (2) hyperexcitable (SICI≤5.5%) and (3) normal cortical excitability (SICI>5.5%). Clinical phenotyping and neurophysiological assessment of LMN function were undertaken, and survival was recorded in the entire cohort.

RESULTS: 417 ALS patients were recruited, of whom 26.4% exhibited cortical inexcitability. Cortical inexcitability was associated with a younger age of disease onset (p<0.05), advanced Awaji criteria (p<0.01) and Kings stage (p<0.01) scores. Additionally, patients with cortical inexcitability had higher UMN score (p<0.01), lower revised ALS Functional Rating Scale score (p<0.01) and reduced upper limb strength score (MRC UL, p<0.01). Patient survival (p=0.398) was comparable across the groups, despite lower riluzole use in the cortical inexcitability patient group (p<0.05).

CONCLUSION: The present study established that cortical inexcitability was associated with a phenotype characterised by prominent UMN signs, greater motor and functional decline, and a younger age of onset. The present findings inform patient management and could improve patient stratification in clinical trials.}, } @article {pmid39135084, year = {2024}, author = {Ma, H and Zhu, M and Chen, M and Li, X and Feng, X}, title = {The role of macrophage plasticity in neurodegenerative diseases.}, journal = {Biomarker research}, volume = {12}, number = {1}, pages = {81}, pmid = {39135084}, issn = {2050-7771}, support = {PX2023037//Beijing Municipal Administration of Hospitals Incubating Program/ ; }, abstract = {Tissue-resident macrophages and recruited macrophages play pivotal roles in innate immunity and the maintenance of brain homeostasis. Investigating the involvement of these macrophage populations in eliciting pathological changes associated with neurodegenerative diseases has been a focal point of research. Dysregulated states of macrophages can compromise clearance mechanisms for pathological proteins such as amyloid-β (Aβ) in Alzheimer's disease (AD) and TDP-43 in Amyotrophic lateral sclerosis (ALS). Additionally, recent evidence suggests that abnormalities in the peripheral clearance of pathological proteins are implicated in the pathogenesis and progression of neurodegenerative diseases. Furthermore, numerous genome-wide association studies have linked genetic risk factors, which alter the functionality of various immune cells, to the accumulation of pathological proteins. This review aims to unravel the intricacies of macrophage biology in both homeostatic conditions and neurodegenerative disorders. To this end, we initially provide an overview of the modifications in receptor and gene expression observed in diverse macrophage subsets throughout development. Subsequently, we outlined the roles of resident macrophages and recruited macrophages in neurodegenerative diseases and the progress of targeted therapy. Finally, we describe the latest advances in macrophage imaging methods and measurement of inflammation, which may provide information and related treatment strategies that hold promise for informing the design of future investigations and therapeutic interventions.}, } @article {pmid39134696, year = {2024}, author = {Visser, BS and Lipiński, WP and Spruijt, E}, title = {The role of biomolecular condensates in protein aggregation.}, journal = {Nature reviews. Chemistry}, volume = {8}, number = {9}, pages = {686-700}, pmid = {39134696}, issn = {2397-3358}, mesh = {Humans ; *Biomolecular Condensates/metabolism/chemistry ; *Protein Aggregates ; Neurodegenerative Diseases/metabolism ; Amyloid/metabolism/chemistry ; Protein Aggregation, Pathological/metabolism ; Proteins/chemistry/metabolism ; }, abstract = {There is an increasing amount of evidence that biomolecular condensates are linked to neurodegenerative diseases associated with protein aggregation, such as Alzheimer's disease and amyotrophic lateral sclerosis, although the mechanisms underlying this link remain elusive. In this Review, we summarize the possible connections between condensates and protein aggregation. We consider both liquid-to-solid transitions of phase-separated proteins and the partitioning of proteins into host condensates. We distinguish five key factors by which the physical and chemical environment of a condensate can influence protein aggregation, and we discuss their relevance in studies of protein aggregation in the presence of biomolecular condensates: increasing the local concentration of proteins, providing a distinct chemical microenvironment, introducing an interface wherein proteins can localize, changing the energy landscape of aggregation pathways, and the presence of chaperones in condensates. Analysing the role of biomolecular condensates in protein aggregation may be essential for a full understanding of amyloid formation and offers a new perspective that can help in developing new therapeutic strategies for the prevention and treatment of neurodegenerative diseases.}, } @article {pmid39134599, year = {2024}, author = {Mikawy, NN and Magdy, N and Mohamed, MH and El-Kosasy, AM}, title = {Green highly sensitive and selective spectroscopic detection of guaifenesin in multiple dosage forms and spiked human plasma.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {18694}, pmid = {39134599}, issn = {2045-2322}, mesh = {*Guaifenesin/analysis/administration & dosage ; Humans ; *Limit of Detection ; *Spectrometry, Fluorescence/methods ; Tablets ; Green Chemistry Technology/methods ; }, abstract = {Guaifenesin (GUA) is determined in dosage forms and plasma using two methods. The spectrofluorimetric technique relies on the measurement of native fluorescence intensity at 302 nm upon excitation wavelength "223 nm". The method was validated according to ICH and FDA guidelines. A concentration range of 0.1-1.1 μg/mL was used, with limit of detection (LOD) and quantification (LOQ) values 0.03 and 0.08 µg/mL, respectively. This method was used to measure GUA in tablets and plasma, with %recovery of 100.44% ± 0.037 and 101.03% ± 0.751. Furthermore, multivariate chemometric-assisted spectrophotometric methods are used for the determination of GUA, paracetamol (PARA), oxomemazine (OXO), and sodium benzoate (SB) in their lab mixtures. The concentration ranges of 2.0-10.0, 4.0-16.0, 2.0-10.0, and 3.0-10.0 µg/mL for OXO, GUA, PARA, and SB; respectively, were used. LOD and LOQ were 0.33, 0.68, 0.28, and 0.29 µg/mL, and 1.00, 2.06, 0.84, and 0.87 µg/mL for PARA, GUA, OXO, and SB. For the suppository application, the partial least square (PLS) model was used with %recovery 98.49% ± 0.5, 98.51% ± 0.64, 100.21% ± 0.36 & 98.13% ± 0.51, although the multivariate curve resolution alternating least-squares (MCR-ALS) model was used with %recovery 101.39 ± 0.45, 99.19 ± 0.2, 100.24 ± 0.12, and 98.61 ± 0.32 for OXO, GUA, PARA, and SB. Analytical Eco-scale and Analytical Greenness Assessment were used to assess the greenness level of our techniques.}, } @article {pmid39134031, year = {2025}, author = {Aziz, M and Kniep, I and Ondruschka, B and Püschel, K and Hessler, C}, title = {Cement Leakage after Augmentation of Osteoporotic Vertebral Bodies.}, journal = {Zeitschrift fur Orthopadie und Unfallchirurgie}, volume = {163}, number = {2}, pages = {146-152}, doi = {10.1055/a-2343-4100}, pmid = {39134031}, issn = {1864-6743}, mesh = {Humans ; Female ; *Bone Cements/adverse effects ; Male ; Aged ; Aged, 80 and over ; Middle Aged ; *Spinal Fractures/surgery/mortality ; Germany/epidemiology ; Risk Factors ; *Vertebroplasty/statistics & numerical data/mortality ; *Osteoporotic Fractures/surgery/mortality ; *Extravasation of Diagnostic and Therapeutic Materials/mortality ; Adult ; Retrospective Studies ; *Postoperative Complications/mortality ; }, abstract = {Der Zementaustritt ist die häufigste Komplikation bei der Zementaugmentation von Wirbelkörpern. In der vorliegenden Studie wurden die Zementaustrittsraten bei Zementaugmentationen an der Wirbelsäule untersucht und potenzielle Risikofaktoren für einen Zementaustritt identifiziert.Es wurden 140 Fälle von 131 Patienten und Patientinnen und 9 Verstorbenen ausgewertet. Insgesamt wurden 258 zementaugmentierte Wirbelkörper untersucht. Die Daten dafür stammen aus den Krankenhausdokumentationen von 131 Patienten und Patientinnen, die sich in 2 orthopädisch-unfallchirurgischen Kliniken in der BRD solchen Operationen unterzogen, sowie aus den Untersuchungen von 9 Sterbefällen im Institut für Rechtsmedizin der Universitätsklinikums Hamburg-Eppendorf.Zementaustritte wurden in 64 der 140 Fälle (45,7%) ermittelt. Lokale Zementaustritte waren mit 73,4% (n = 47) die häufigste Austrittsart. Venöse Austritte wurden in 15 Fällen (23,4%) und Lungenzementembolisationen in 2 Fällen (3,1%) evaluiert. Innerhalb des Kollektivs der retrospektiv untersuchten Fälle (n = 131) erlitt lediglich 1 Patient (0,8%) einen symptomatischen Zementaustritt. Als Risikofaktoren für Zementaustritte konnten Zementaugmentationen von Frakturen an Lendenwirbelkörpern sowie eine hohe applizierte Zementmenge identifiziert werden.Sowohl die Daten in der assoziierten Literatur als auch die Ergebnisse dieser Arbeit belegen eine hohe Inzidenz von Zementaustritten nach Wirbelkörperaugmentationen. Trotz des geringen prozentualen Anteils symptomatischer Fälle sollten bei der Planung und Durchführung von Zementaugmentationen an Wirbelkörpern die möglichen Einflussfaktoren für einen Zementaustritt berücksichtigt und in die OP-Planung einbezogen werden.}, } @article {pmid39131911, year = {2024}, author = {Ikeda, A and Meng, H and Taniguchi, D and Mio, M and Funayama, M and Nishioka, K and Yoshida, M and Li, Y and Yoshino, H and Inoshita, T and Shiba-Fukushima, K and Okubo, Y and Sakurai, T and Amo, T and Aiba, I and Saito, Y and Saito, Y and Murayama, S and Atsuta, N and Nakamura, R and Tohnai, G and Izumi, Y and Morita, M and Tamura, A and Kano, O and Oda, M and Kuwabara, S and Yamashita, T and Sone, J and Kaji, R and Sobue, G and Imai, Y and Hattori, N}, title = {CHCHD2 P14L, found in amyotrophic lateral sclerosis, exhibits cytoplasmic mislocalization and alters Ca[2+] homeostasis.}, journal = {PNAS nexus}, volume = {3}, number = {8}, pages = {pgae319}, pmid = {39131911}, issn = {2752-6542}, abstract = {CHCHD2 and CHCHD10, linked to Parkinson's disease and amyotrophic lateral sclerosis-frontotemporal dementia (ALS), respectively, are mitochondrial intermembrane proteins that form a heterodimer. This study aimed to investigate the impact of the CHCHD2 P14L variant, implicated in ALS, on mitochondrial function and its subsequent effects on cellular homeostasis. The missense variant of CHCHD2, P14L, found in a cohort of patients with ALS, mislocalized CHCHD2 to the cytoplasm, leaving CHCHD10 in the mitochondria. Drosophila lacking the CHCHD2 ortholog exhibited mitochondrial degeneration. In contrast, human CHCHD2 P14L, but not wild-type human CHCHD2, failed to suppress this degeneration, suggesting that P14L is a pathogenic variant. The mitochondrial Ca[2+] buffering capacity was reduced in Drosophila neurons expressing human CHCHD2 P14L. The altered Ca[2+]-buffering phenotype was also observed in cultured human neuroblastoma SH-SY5Y cells expressing CHCHD2 P14L. In these cells, transient elevation of cytoplasmic Ca[2+] facilitated the activation of calpain and caspase-3, accompanied by the processing and insolubilization of TDP-43. These observations suggest that CHCHD2 P14L causes abnormal Ca[2+] dynamics and TDP-43 aggregation, reflecting the pathophysiology of ALS.}, } @article {pmid39130445, year = {2024}, author = {Phipps, AJ and Dwyer, S and Collins, JM and Kabir, F and Atkinson, RA and Chowdhury, MA and Matthews, L and Dixit, D and Terry, RS and Smith, J and Gueven, N and Bennett, W and Cook, AL and King, AE and Perry, S}, title = {HDAC6 inhibition as a mechanism to prevent neurodegeneration in the mSOD1[G93A] mouse model of ALS.}, journal = {Heliyon}, volume = {10}, number = {14}, pages = {e34587}, pmid = {39130445}, issn = {2405-8440}, abstract = {The loss of upper and lower motor neurons, and their axons is central to the loss of motor function and death in amyotrophic lateral sclerosis (ALS). Due to the diverse range of genetic and environmental factors that contribute to the pathogenesis of ALS, there have been difficulties in developing effective therapies for ALS. One emerging dichotomy is that protection of the neuronal cell soma does not prevent axonal vulnerability and degeneration, suggesting the need for targeted therapeutics to prevent axon degeneration. Post-translational modifications of protein acetylation can alter the function, stability and half-life of individual proteins, and can be enzymatically modified by histone acetyltransferases (HATs) and histone deacetyltransferases (HDACs), which add, or remove acetyl groups, respectively. Maintenance of post-translational microtubule acetylation has been suggested as a mechanism to stabilize axons, prevent axonal loss and neurodegeneration in ALS. This study used an orally dosed potent HDAC6 inhibitor, ACY-738, prevent deacetylation and stabilize microtubules in the mSOD1[G93A] mouse model of ALS. Co-treatment with riluzole was performed to determine any effects or drug interactions and potentially enhance preclinical research translation. This study shows ACY-738 treatment increased acetylation of microtubules in the spinal cord of mSOD1[G93A] mice, reduced lower motor neuron degeneration in female mice, ameliorated reduction in peripheral nerve axon puncta size, but did not prevent overt motor function decline. The current study also shows peripheral nerve axon puncta size to be partially restored after treatment with riluzole and highlights the importance of co-treatment to measure the potential effects of therapeutics in ALS.}, } @article {pmid39128808, year = {2024}, author = {Farhangian, M and Azarafrouz, F and Valian, N and Dargahi, L}, title = {The role of interferon beta in neurological diseases and its potential therapeutic relevance.}, journal = {European journal of pharmacology}, volume = {981}, number = {}, pages = {176882}, doi = {10.1016/j.ejphar.2024.176882}, pmid = {39128808}, issn = {1879-0712}, mesh = {Humans ; Animals ; *Interferon-beta/therapeutic use/metabolism ; Nervous System Diseases/drug therapy/metabolism ; Signal Transduction/drug effects ; }, abstract = {Interferon beta (IFNβ) is a member of the type-1 interferon family and has various immunomodulatory functions in neuropathological conditions. Although the level of IFNβ is low under healthy conditions, it is increased during inflammatory processes to protect the central nervous system (CNS). In particular, microglia and astrocytes are the main sources of IFNβ upon inflammatory insult in the CNS. The protective effects of IFNβ are well characterized in reducing the progression of multiple sclerosis (MS); however, little is understood about its effects in other neurological/neurodegenerative diseases. In this review, different types of IFNs and their signaling pathways will be described. Then we will focus on the potential role and therapeutic effect of IFNβ in several CNS-related diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, stroke, spinal cord injury, prion disease and spinocerebellar ataxia 7.}, } @article {pmid39128727, year = {2024}, author = {George, G and Ajayan, A and Varkey, J and Pandey, NK and Chen, J and Langen, R}, title = {TDP43 and huntingtin Exon-1 undergo a conformationally specific interaction that strongly alters the fibril formation of both proteins.}, journal = {The Journal of biological chemistry}, volume = {300}, number = {9}, pages = {107660}, pmid = {39128727}, issn = {1083-351X}, support = {R01 NS118859/NS/NINDS NIH HHS/United States ; R01 NS120704/NS/NINDS NIH HHS/United States ; R01 NS125769/NS/NINDS NIH HHS/United States ; }, mesh = {*Huntingtin Protein/metabolism/genetics/chemistry ; Humans ; *DNA-Binding Proteins/metabolism/genetics/chemistry ; *Exons ; Amyloid/metabolism/chemistry ; Protein Aggregates ; Protein Aggregation, Pathological/metabolism/genetics ; Protein Binding ; Protein Conformation ; Protein Domains ; }, abstract = {Protein aggregation is a common feature of many neurodegenerative diseases. In Huntington's disease, mutant huntingtin is the primary aggregating protein, but the aggregation of other proteins, such as TDP43, is likely to further contribute to toxicity. Moreover, mutant huntingtin is also a risk factor for TDP pathology in ALS. Despite this co-pathology of huntingtin and TDP43, it remains unknown whether these amyloidogenic proteins directly interact with each other. Using a combination of biophysical methods, we show that the aggregation-prone regions of both proteins, huntingtin exon-1 (Httex1) and the TDP43 low complexity domain (TDP43-LCD), interact in a conformationally specific manner. This interaction significantly slows Httex1 aggregation, while it accelerates TDP43-LCD aggregation. A key intermediate responsible for both effects is a complex formed by liquid TDP43-LCD condensates and Httex1 fibrils. This complex shields seeding competent surfaces of Httex1 fibrils from Httex1 monomers, which are excluded from the condensates. In contrast, TDP43-LCD condensates undergo an accelerated liquid-to-solid transition upon exposure to Httex1 fibrils. Cellular studies show co-aggregation of untagged Httex1 with TDP43. This interaction causes mislocalization of TDP43, which has been linked to TDP43 toxicity. The protection from Httex1 aggregation in lieu of TDP43-LCD aggregation is interesting, as it mirrors what has been found in disease models, namely that TDP43 can protect from huntingtin toxicity, while mutant huntingtin can promote TDP43 pathology. These results suggest that direct protein interaction could, at least in part, be responsible for the linked pathologies of both proteins.}, } @article {pmid39128005, year = {2024}, author = {Knupp, J and Chen, YJ and Wang, E and Arvan, P and Tsai, B}, title = {Sigma-1 receptor recruits LC3 mRNA to ER-associated omegasomes to promote localized LC3 translation enabling functional autophagy.}, journal = {Cell reports}, volume = {43}, number = {8}, pages = {114619}, pmid = {39128005}, issn = {2211-1247}, support = {F31 DK128868/DK/NIDDK NIH HHS/United States ; P30 DK020572/DK/NIDDK NIH HHS/United States ; R01 AI170514/AI/NIAID NIH HHS/United States ; R01 DK111174/DK/NIDDK NIH HHS/United States ; }, mesh = {*Receptors, sigma/metabolism/genetics ; *Sigma-1 Receptor ; *Autophagy ; *Microtubule-Associated Proteins/metabolism/genetics ; *Endoplasmic Reticulum/metabolism ; Humans ; *RNA, Messenger/metabolism/genetics ; *3' Untranslated Regions/genetics ; *Protein Biosynthesis ; Ribosomes/metabolism ; Animals ; Autophagosomes/metabolism ; HeLa Cells ; }, abstract = {Autophagosome formation initiated on the endoplasmic reticulum (ER)-associated omegasome requires LC3. Translational regulation of LC3 biosynthesis is unexplored. Here we demonstrate that LC3 mRNA is recruited to omegasomes by directly binding to the ER transmembrane Sigma-1 receptor (S1R). Cell-based and in vitro reconstitution experiments show that S1R interacts with the 3' UTR of LC3 mRNA and ribosomes to promote LC3 translation. Strikingly, the 3' UTR of LC3 is also required for LC3 protein lipidation, thereby linking the mRNA-3' UTR to LC3 function. An autophagy-defective S1R mutant responsible for amyotrophic lateral sclerosis cannot bind LC3 mRNA or induce LC3 translation. We propose a model wherein S1R de-represses LC3 mRNA via its 3' UTR at the ER, enabling LC3 biosynthesis and lipidation. Because several other LC3-related proteins use the same mechanism, our data reveal a conserved pathway for localized translation essential for autophagosome biogenesis with insights illuminating the molecular basis of a neurodegenerative disease.}, } @article {pmid39127445, year = {2024}, author = {Wang, MY and Zhou, Y and Li, WL and Zhu, LQ and Liu, D}, title = {Friend or foe: Lactate in neurodegenerative diseases.}, journal = {Ageing research reviews}, volume = {101}, number = {}, pages = {102452}, doi = {10.1016/j.arr.2024.102452}, pmid = {39127445}, issn = {1872-9649}, mesh = {Humans ; *Neurodegenerative Diseases/metabolism ; *Lactic Acid/metabolism ; Animals ; }, abstract = {Lactate, a byproduct of glycolysis, was considered as a metabolic waste until identified by studies on the Warburg effect. Increasing evidence elucidates that lactate functions as energy fuel, signaling molecule, and donor for protein lactylation. Altered lactate utilization is a common metabolic feature of the onset and progression of neurodegenerative diseases, such as Alzheimer's disease, multiple sclerosis, amyotrophic lateral sclerosis, Parkinson's disease and Huntington's disease. This review offers an overview of lactate metabolism from the perspective of production, transportation and clearance, and the role of lactate in neurodegenerative progression, as well as a summary of protein lactylation and the signaling function of lactate in neurodegenerative diseases. Besides, this review delves into the dual roles of changed lactate metabolism during neurodegeneration and explores prospective therapeutic methods targeting lactate. We propose that elucidating the correlation between lactate and neurodegeneration is pivotal for exploring innovative therapeutic interventions for neurodegenerative diseases.}, } @article {pmid39126873, year = {2024}, author = {Vacchiano, V and Di Stasi, V and Teodorani, L and Faini, C and Morabito, F and Liguori, R}, title = {Comparative assessment of MScanFit MUNE and quantitative EMG in amyotrophic lateral sclerosis diagnosis: A prospective study.}, journal = {Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology}, volume = {166}, number = {}, pages = {66-73}, doi = {10.1016/j.clinph.2024.07.017}, pmid = {39126873}, issn = {1872-8952}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology/diagnosis ; *Electromyography/methods ; Male ; Female ; Middle Aged ; Aged ; Prospective Studies ; *Motor Neurons/physiology ; *Action Potentials/physiology ; *Muscle, Skeletal/physiopathology ; Adult ; }, abstract = {OBJECTIVE: Motor Unit Number Estimation (MUNE) techniques are crucial in assessing lower motor neuron loss. MScanFit MUNE (MScanFit) is a novel tool which estimates MUNE values from compound muscle action potential (CMAP) scans by considering the probabilistic nature of motor unit firing. We conducted a prospective study to evaluate the diagnostic utility of MScanFit compared to quantitative electromyography (qEMG) in ALS patients.

METHODS: We enrolled 35 patients diagnosed with amyotrophic lateral sclerosis (ALS) and 14 healthy controls, assessing qEMG and MScanFit MUNE in abductor pollicis brevis, abductor digiti minimi and tibialis anterior muscles.

RESULTS: We found higher sensitivity of qEMG in detecting abnormalities compared to MScanFit, with a high concordance rate between the two techniques. Notably, a few muscles exhibited abnormal MUNE but normal qEMG findings, suggesting a potential complementary role for MScanFit in ALS diagnosis. Neurophysiological parameters from MScanFit showed good correlations with qEMG measures. Subclinical neurophysiological involvement was observed in muscles with normal strength, emphasizing the importance of sensitive diagnostic tools.

CONCLUSION: MScanFit demonstrated validity in distinguishing ALS patients from healthy subjects and correlated well with qEMG parameters.

SIGNIFICANCE: Our study confirmed the diagnostic utility of MScanFit MUNE in ALS, highlighting its role as a supplementary diagnostic tool.}, } @article {pmid39126786, year = {2024}, author = {Neumann, M and Kothare, H and Ramanarayanan, V}, title = {Multimodal speech biomarkers for remote monitoring of ALS disease progression.}, journal = {Computers in biology and medicine}, volume = {180}, number = {}, pages = {108949}, pmid = {39126786}, issn = {1879-0534}, support = {R42 DC019877/DC/NIDCD NIH HHS/United States ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology ; Male ; *Disease Progression ; Female ; Middle Aged ; Aged ; Speech/physiology ; Biomarkers ; Adult ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that severely impacts affected persons' speech and motor functions, yet early detection and tracking of disease progression remain challenging. The current gold standard for monitoring ALS progression, the ALS functional rating scale - revised (ALSFRS-R), is based on subjective ratings of symptom severity, and may not capture subtle but clinically meaningful changes due to a lack of granularity. Multimodal speech measures which can be automatically collected from patients in a remote fashion allow us to bridge this gap because they are continuous-valued and therefore, potentially more granular at capturing disease progression. Here we investigate the responsiveness and sensitivity of multimodal speech measures in persons with ALS (pALS) collected via a remote patient monitoring platform in an effort to quantify how long it takes to detect a clinically-meaningful change associated with disease progression. We recorded audio and video from 278 participants and automatically extracted multimodal speech biomarkers (acoustic, orofacial, linguistic) from the data. We find that the timing alignment of pALS speech relative to a canonical elicitation of the same prompt and the number of words used to describe a picture are the most responsive measures at detecting such change in both pALS with bulbar (n = 36) and non-bulbar onset (n = 107). Interestingly, the responsiveness of these measures is stable even at small sample sizes. We further found that certain speech measures are sensitive enough to track bulbar decline even when there is no patient-reported clinical change, i.e. the ALSFRS-R speech score remains unchanged at 3 out of a total possible score of 4. The findings of this study have the potential to facilitate improved, accelerated and cost-effective clinical trials and care.}, } @article {pmid39126203, year = {2024}, author = {Tabuchi, R and Momozawa, Y and Hayashi, Y and Noma, H and Ichijo, H and Fujisawa, T}, title = {SoDCoD: a comprehensive database of Cu/Zn superoxide dismutase conformational diversity caused by ALS-linked gene mutations and other perturbations.}, journal = {Database : the journal of biological databases and curation}, volume = {2024}, number = {}, pages = {0}, pmid = {39126203}, issn = {1758-0463}, support = {JP21H04760 JP22H04636 JP22H04804 JP22K06610 JP23K14143//Japan Society for the Promotion of Science/ ; JP21gm5010001//Japan Agency for Medical Research and Development/ ; //SERIKA FUND/ ; 2023-ISMCRP-2033//the ISM Cooperative Research Program/ ; //the researcher exchange promotion program of ROIS (Research Organization of Information and Systems)/ ; JPMJMS2022-18//Japan Science and Technology Agency/ ; JP21H04760 JP22H04636 JP22H04804 JP22K06610 JP23K14143//Japan Society for the Promotion of Science/ ; JP21gm5010001//Japan Agency for Medical Research and Development/ ; //SERIKA FUND/ ; 2023-ISMCRP-2033//the ISM Cooperative Research Program/ ; //the researcher exchange promotion program of ROIS (Research Organization of Information and Systems)/ ; JPMJMS2022-18//Japan Science and Technology Agency/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/genetics/enzymology ; Humans ; *Mutation ; *Superoxide Dismutase-1/genetics/chemistry/metabolism ; Databases, Protein ; Protein Conformation ; Databases, Genetic ; Superoxide Dismutase/genetics/chemistry/metabolism ; }, abstract = {A structural alteration in copper/zinc superoxide dismutase (SOD1) is one of the common features caused by amyotrophic lateral sclerosis (ALS)-linked mutations. Although a large number of SOD1 variants have been reported in ALS patients, the detailed structural properties of each variant are not well summarized. We present SoDCoD, a database of superoxide dismutase conformational diversity, collecting our comprehensive biochemical analyses of the structural changes in SOD1 caused by ALS-linked gene mutations and other perturbations. SoDCoD version 1.0 contains information about the properties of 188 types of SOD1 mutants, including structural changes and their binding to Derlin-1, as well as a set of genes contributing to the proteostasis of mutant-like wild-type SOD1. This database provides valuable insights into the diagnosis and treatment of ALS, particularly by targeting conformational alterations in SOD1. Database URL: https://fujisawagroup.github.io/SoDCoDweb/.}, } @article {pmid39126144, year = {2024}, author = {Briones, MRS and Campos, JH and Ferreira, RC and Schneper, L and Santos, IM and Antoneli, FM and , and Broach, JR}, title = {Mitochondrial genome variants associated with amyotrophic lateral sclerosis and their haplogroup distribution.}, journal = {Muscle & nerve}, volume = {70}, number = {4}, pages = {862-872}, pmid = {39126144}, issn = {1097-4598}, support = {//Tow Foundation/ ; //NIH/ ; 2013/07838-0//FAPESP/ ; 2014/25602-6//FAPESP/ ; //CAPES/ ; 303912/2017-0//CNPq/ ; T32 LM012415/LM/NLM NIH HHS/United States ; 19-SI-459//ALS Association/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics ; *Genome, Mitochondrial/genetics ; Male ; Female ; *Genome-Wide Association Study ; Middle Aged ; Haplotypes ; Polymorphism, Single Nucleotide ; Genetic Predisposition to Disease/genetics ; Aged ; Genetic Variation/genetics ; }, abstract = {INTRODUCTION/AIMS: Amyotrophic lateral sclerosis (ALS) may be familial or sporadic, and twin studies have revealed that even sporadic forms have a significant genetic component. Variants in 55 nuclear genes have been associated with ALS and although mitochondrial dysfunction is observed in ALS, variants in mitochondrial genomes (mitogenomes) have not yet been tested for association with ALS. The aim of this study was to determine whether mitogenome variants are associated with ALS.

METHODS: We conducted a genome-wide association study (GWAS) in mitogenomes of 1965 ALS patients and 2547 controls.

RESULTS: We identified 51 mitogenome variants with p values <10[-7], of which 13 had odds ratios (ORs) >1, in genes RNR1, ND1, CO1, CO3, ND5, ND6, and CYB, while 38 variants had OR <1 in genes RNR1, RNA2, ND1, ND2, CO2, ATP8, ATP6, CO3, ND3, ND4, ND5, ND6, and CYB. The frequencies of haplogroups H, U, and L, the most frequent in our ALS data set, were the same in different onset sites (bulbar, limb, spinal, and axial). Also, intra-haplogroup GWAS revealed unique ALS-associated variants in haplogroups L and U.

DISCUSSION: Our study shows that mitogenome single nucleotide variants (SNVs) are associated with ALS and suggests that these SNVs could be included in routine genetic testing for ALS and that mitochondrial replacement therapy has the potential to serve as a basis for ALS treatment.}, } @article {pmid39126066, year = {2024}, author = {Mejzini, R and Caruthers, MH and Schafer, B and Kostov, O and Sudheendran, K and Ciba, M and Danielsen, M and Wilton, S and Akkari, PA and Flynn, LL}, title = {Allele-Selective Thiomorpholino Antisense Oligonucleotides as a Therapeutic Approach for Fused-in-Sarcoma Amyotrophic Lateral Sclerosis.}, journal = {International journal of molecular sciences}, volume = {25}, number = {15}, pages = {}, pmid = {39126066}, issn = {1422-0067}, support = {2322//Motor Neurone Disease Research Australia/ ; }, mesh = {Humans ; *Oligonucleotides, Antisense/therapeutic use/genetics ; *Amyotrophic Lateral Sclerosis/genetics/drug therapy/therapy ; *RNA-Binding Protein FUS/genetics ; *Alleles ; Fibroblasts/metabolism/drug effects ; Gene Knockdown Techniques ; Morpholinos/therapeutic use/genetics ; }, abstract = {Pathogenic variations in the fused in sarcoma (FUS) gene are associated with rare and aggressive forms of amyotrophic lateral sclerosis (ALS). As FUS-ALS is a dominant disease, a targeted, allele-selective approach to FUS knockdown is most suitable. Antisense oligonucleotides (AOs) are a promising therapeutic platform for treating such diseases. In this study, we have explored the potential for allele-selective knockdown of FUS. Gapmer-type AOs targeted to two common neutral polymorphisms in FUS were designed and evaluated in human fibroblasts. AOs had either methoxyethyl (MOE) or thiomorpholino (TMO) modifications. We found that the TMO modification improved allele selectivity and efficacy for the lead sequences when compared to the MOE counterparts. After TMO-modified gapmer knockdown of the target allele, up to 93% of FUS transcripts detected were from the non-target allele. Compared to MOE-modified AOs, the TMO-modified AOs also demonstrated reduced formation of structured nuclear inclusions and SFPQ aggregation that can be triggered by phosphorothioate-containing AOs. How overall length and gap length of the TMO-modified AOs affected allele selectivity, efficiency and off-target gene knockdown was also evaluated. We have shown that allele-selective knockdown of FUS may be a viable therapeutic strategy for treating FUS-ALS and demonstrated the benefits of the TMO modification for allele-selective applications.}, } @article {pmid39125740, year = {2024}, author = {Bernard, E and Cluse, F and Bohic, A and Hermier, M and Raoul, C and Leblanc, P and Guissart, C}, title = {A Novel De Novo Missense Mutation in KIF1A Associated with Young-Onset Upper-Limb Amyotrophic Lateral Sclerosis.}, journal = {International journal of molecular sciences}, volume = {25}, number = {15}, pages = {}, pmid = {39125740}, issn = {1422-0067}, mesh = {Humans ; *Kinesins/genetics ; *Amyotrophic Lateral Sclerosis/genetics ; Female ; *Mutation, Missense ; Adult ; Upper Extremity/physiopathology/pathology ; Magnetic Resonance Imaging ; }, abstract = {We investigate the etiology of amyotrophic lateral sclerosis (ALS) in a 35-year-old woman presenting with progressive weakness in her left upper limb. Prior to sequencing, a comprehensive neurological work-up was performed, including neurological examination, electrophysiology, biomarker assessment, and brain and spinal cord MRI. Six months before evaluation, the patient experienced weakness and atrophy in her left hand, accompanied by brisk reflexes and Hoffman sign in the same arm. Electroneuromyography revealed lower motor neuron involvement in three body regions. Neurofilament light chains were elevated in her cerebrospinal fluid. Brain imaging showed asymmetrical T2 hyperintensity of the corticospinal tracts and T2 linear hypointensity of the precentral gyri. Trio genome sequencing identified a likely pathogenic de novo variant in the KIF1A gene (NM_001244008.2): c.574A>G, p.(Ile192Val). Pathogenic variants in KIF1A have been associated with a wide range of neurological manifestations called KIF1A-associated neurological diseases (KAND). This report describes a likely pathogenic de novo variant in KIF1A associated with ALS, expanding the phenotypic spectrum of KAND and our understanding of the pathophysiology of ALS.}, } @article {pmid39124808, year = {2024}, author = {Miyaue, N and Yamanishi, Y and Ito, Y and Ando, R and Nagai, M}, title = {CSF Neopterin Levels Are Elevated in Various Neurological Diseases and Aging.}, journal = {Journal of clinical medicine}, volume = {13}, number = {15}, pages = {}, pmid = {39124808}, issn = {2077-0383}, abstract = {Background/Objectives: Cerebrospinal fluid (CSF) neopterin reflects inflammation of the central nervous system (CNS) and is a potentially useful biomarker for neuroinflammatory assessment and differential diagnosis. However, its optimal cut-off level in adult patients with neurological disease has not been established and it has not been adequately studied in controls. We aimed to determine its usefulness as a biomarker of neuroinflammation and the effect of age on its level. Methods: In this retrospective study, CSF neopterin was evaluated in 652 patients in 38 disease groups. Its levels were analyzed with high-performance liquid chromatography with fluorometric detection. Results: A receiver operating characteristic analysis revealed that the optimal cut-off value of 33.57 pmol/mL for CSF neopterin distinguished the control and meningitis/encephalitis groups with a sensitivity of 100.0% and specificity of 94.4%. In the control group, which consisted of 170 participants (99 men and 71 women; mean ± standard deviation age, 52.56 ± 17.99 years), age was significantly positively correlated with CSF protein (r = 0.474, p < 0.001) and CSF neopterin (r = 0.476, p < 0.001) levels but not with CSF cell count (r = 0.144, p = 0.061). Both male and female controls exhibited significant increases in CSF neopterin levels with age. Similarly, the CSF neopterin level was significantly positively correlated with age in patients with amyotrophic lateral sclerosis, independently of disease duration and respiratory function. Conclusions: CSF neopterin levels were elevated in patients with various CNS diseases, reflecting CNS inflammation; they were also elevated with age. Prospective studies are required to establish CSF neopterin as a sensitive biomarker of neuroinflammation.}, } @article {pmid39123212, year = {2024}, author = {Wang, X and Pan, W and Sun, C and Yang, H and Cheng, Z and Yan, F and Ma, G and Shang, Y and Zhang, R and Gao, C and Liu, L and Zhang, H}, title = {Creating large-scale genetic diversity in Arabidopsis via base editing-mediated deep artificial evolution.}, journal = {Genome biology}, volume = {25}, number = {1}, pages = {215}, pmid = {39123212}, issn = {1474-760X}, support = {TSQN202103160//Taishan Scholar Foundation of Shandong Province/ ; ZR202103010168//Excellent Youth Foundation of Shandong Scientific Committee/ ; 2022YFD1201700//National Key R&D Program of China/ ; }, mesh = {*Arabidopsis/genetics ; *Gene Editing/methods ; *Genetic Variation ; CRISPR-Cas Systems ; Directed Molecular Evolution ; Alleles ; Mutation ; Plant Breeding/methods ; Herbicide Resistance/genetics ; }, abstract = {BACKGROUND: Base editing is a powerful tool for artificial evolution to create allelic diversity and improve agronomic traits. However, the great evolutionary potential for every sgRNA target has been overlooked. And there is currently no high-throughput method for generating and characterizing as many changes in a single target as possible based on large mutant pools to permit rapid gene directed evolution in plants.

RESULTS: In this study, we establish an efficient germline-specific evolution system to screen beneficial alleles in Arabidopsis which could be applied for crop improvement. This system is based on a strong egg cell-specific cytosine base editor and the large seed production of Arabidopsis, which enables each T1 plant with unedited wild type alleles to produce thousands of independent T2 mutant lines. It has the ability of creating a wide range of mutant lines, including those containing atypical base substitutions, and as well providing a space- and labor-saving way to store and screen the resulting mutant libraries. Using this system, we efficiently generate herbicide-resistant EPSPS, ALS, and HPPD variants that could be used in crop breeding.

CONCLUSIONS: Here, we demonstrate the significant potential of base editing-mediated artificial evolution for each sgRNA target and devised an efficient system for conducting deep evolution to harness this potential.}, } @article {pmid39122743, year = {2024}, author = {Shin, B and Kwon, Y and Mittaz, M and Kim, H and Xu, X and Kim, E and Lee, YJ and Lee, J and Yeo, WH and Choo, HJ}, title = {All-in-one wearable drug efficacy assessment systems for bulbar muscle function using amyotrophic lateral sclerosis animal models.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {6803}, pmid = {39122743}, issn = {2041-1723}, support = {R21 EB031535/EB/NIBIB NIH HHS/United States ; UL1 TR002378/TR/NCATS NIH HHS/United States ; R21EB031535//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/physiopathology/drug therapy ; Animals ; *Disease Models, Animal ; *Wearable Electronic Devices ; *Electromyography/methods ; Drug Evaluation, Preclinical ; Deglutition Disorders/physiopathology/etiology ; Muscle, Skeletal/drug effects/physiopathology/innervation ; Humans ; Male ; Motor Neurons/drug effects/physiology ; Rats ; }, abstract = {Preclinical studies are crucial for developing amyotrophic lateral sclerosis drugs. Current FDA-approved drugs have been created by monitoring limb muscle function and histological analysis of amyotrophic lateral sclerosis model animals. Drug candidates for this disease have yet to be tested for bulbar-onset type due to the limitations of traditional preclinical tools: excessive animal use and discrete detection of disease progress. Here, our study introduces an all-in-one, wireless, integrated wearable system for facilitating continuous drug efficacy assessment of dysphagia-related muscles in animals during natural eating behaviors. By incorporating a kirigami-based strain-isolation mechanism, this device mounted on the skin of animals mitigates electromyography signal contamination caused by unpredictable animal movements. Our findings indicate this system, measuring the progression of motor neuron denervation, offers high precision in monitoring drug effects on dysphagia-responsible bulbar muscles. This study paves the way for more humane and efficient approaches to developing treatment solutions for degenerative neuromuscular diseases.}, } @article {pmid39122453, year = {2024}, author = {Khan, S and Bano, N and Ahamad, S and John, U and Dar, NJ and Bhat, SA}, title = {Excitotoxicity, Oxytosis/Ferroptosis, and Neurodegeneration: Emerging Insights into Mitochondrial Mechanisms.}, journal = {Aging and disease}, volume = {16}, number = {5}, pages = {2504-2543}, pmid = {39122453}, issn = {2152-5250}, mesh = {Humans ; *Neurodegenerative Diseases/metabolism/pathology/physiopathology ; *Mitochondria/metabolism/pathology ; Oxidative Stress ; *Ferroptosis/physiology ; Mitophagy ; Animals ; Energy Metabolism ; }, abstract = {Mitochondrial dysfunction plays a pivotal role in the development of age-related diseases, particularly neurodegenerative disorders. The etiology of mitochondrial dysfunction involves a multitude of factors that remain elusive. This review centers on elucidating the role(s) of excitotoxicity, oxytosis/ferroptosis and neurodegeneration within the context of mitochondrial bioenergetics, biogenesis, mitophagy and oxidative stress and explores their intricate interplay in the pathogenesis of neurodegenerative diseases. The effective coordination of mitochondrial turnover processes, notably mitophagy and biogenesis, is assumed to be critically important for cellular resilience and longevity. However, the age-associated decrease in mitophagy impedes the elimination of dysfunctional mitochondria, consequently impairing mitochondrial biogenesis. This deleterious cascade results in the accumulation of damaged mitochondria and deterioration of cellular functions. Both excitotoxicity and oxytosis/ferroptosis have been demonstrated to contribute significantly to the pathophysiology of neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's Disease (HD), Amyotrophic Lateral Sclerosis (ALS) and Multiple Sclerosis (MS). Excitotoxicity, characterized by excessive glutamate signaling, initiates a cascade of events involving calcium dysregulation, energy depletion, and oxidative stress and is intricately linked to mitochondrial dysfunction. Furthermore, emerging concepts surrounding oxytosis/ferroptosis underscore the importance of iron-dependent lipid peroxidation and mitochondrial engagement in the pathogenesis of neurodegeneration. This review not only discusses the individual contributions of excitotoxicity and ferroptosis but also emphasizes their convergence with mitochondrial dysfunction, a key driver of neurodegenerative diseases. Understanding the intricate crosstalk between excitotoxicity, oxytosis/ferroptosis, and mitochondrial dysfunction holds potential to pave the way for mitochondrion-targeted therapeutic strategies. Such strategies, with a focus on bioenergetics, biogenesis, mitophagy, and oxidative stress, emerge as promising avenues for therapeutic intervention.}, } @article {pmid39122262, year = {2024}, author = {Wang, S and Jiang, Q and Zheng, X and Wei, Q and Lin, J and Yang, T and Xiao, Y and Li, C and Shang, H}, title = {Genotype-phenotype correlation of SQSTM1 variants in patients with amyotrophic lateral sclerosis.}, journal = {Journal of medical genetics}, volume = {61}, number = {10}, pages = {966-972}, doi = {10.1136/jmg-2023-109569}, pmid = {39122262}, issn = {1468-6244}, mesh = {Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; *Amyotrophic Lateral Sclerosis/genetics/pathology/epidemiology ; Frontotemporal Dementia/genetics/pathology ; Gene Frequency ; *Genetic Association Studies ; Genetic Predisposition to Disease ; Genotype ; Mutation ; Phenotype ; *Sequestosome-1 Protein/genetics ; Young Adult ; Aged, 80 and over ; }, abstract = {BACKGROUND: Several variants of sequestosome 1 (SQSTM1) were screened in patients with amyotrophic lateral sclerosis (ALS), while the pathogenicity and genotype-phenotype correlation remains unclear.

METHODS: We screened variants of SQSTM1 gene in 2011 Chinese patients with ALS and performed a burden analysis focusing on the rare variants. Furthermore, we conducted a comprehensive analysis of patients with variants of SQSTM1 gene in patients with ALS from our cohort and published studies.

RESULTS: In our cohort, we identified 32 patients with 25 different SQSTM1 variants with a mutant frequency of 1.6%. Notably, 26% (5/19) of the patients with ALS with SQSTM1 variant in our cohort had comorbid cognitive impairment and 43% (3/7) of them had behavioural variant frontotemporal dementia (FTD). Our meta-analysis found a total frequency of SQSTM1 variants in 7183 patients with ALS was 2.4%; burden analysis indicated that patients with ALS had enrichment of ultra-rare (minor allele frequency<0.01%) probably pathogenic variants in SQSTM1. Most variants were missense variants and distributed in various domains of p62 protein, some of which might be related to comorbidities of Paget's disease of bone and FTD.

CONCLUSION: Our study established the largest cohort of patients with ALS with SQSTM1 variants, expanded the mutation spectrum and investigated the genotype-phenotype correlations of SQSTM1 variants.}, } @article {pmid39122006, year = {2024}, author = {Chen, X and Wei, Q and Yang, Z and Chen, X and Guo, S and Jiang, M and Wang, M}, title = {Structural basis for RNA recognition by the C-terminal RRM domain of human RBM45.}, journal = {The Journal of biological chemistry}, volume = {300}, number = {9}, pages = {107640}, pmid = {39122006}, issn = {1083-351X}, mesh = {Humans ; *RNA-Binding Proteins/metabolism/chemistry/genetics ; *RNA/metabolism/chemistry ; Crystallography, X-Ray ; Protein Domains ; Protein Binding ; DNA, Single-Stranded/metabolism/chemistry/genetics ; Models, Molecular ; Nerve Tissue Proteins ; }, abstract = {RBM45 is an RNA-binding protein with roles in neural development by regulating RNA splicing. Its dysfunction and aggregation are associated with neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and frontotemporal lobar dementia (FTLD). RBM45 harbors three RRM domains that potentially bind RNA. While the recognitions of RNA by its N-terminal tandem RRM domains (RRM1 and RRM2) have been well understood, the RNA-binding property of its C-terminal RRM (RRM3) remains unclear. In this work, we identified that the RRM3 of the RBM45 sequence specifically binds RNA with a GACG sequence, similar but not identical to those recognized by the RRM1 and RRM2. Further, we determined the crystal structure of RBM45[RRM3] in complex with a GACG sequence-containing single-stranded DNA. Our structural results, together with the RNA-binding assays of mutants at key amino acid residues, revealed the molecular mechanism by which RBM45[RRM3] recognizes an RNA sequence. Our finding on the RNA-binding property of the individual RRM module of RBM45 provides the foundation for unraveling the RNA-binding characteristics of full-length RBM45 and for understanding the biological functions of RBM45.}, } @article {pmid39121134, year = {2024}, author = {Roos, A and Häusler, M and Kollipara, L and Topf, A and Preusse, C and Stucka, R and Nolte, K and Strom, T and Berutti, R and Jiang, X and Koll, R and Lochmüller, H and Schacht, SM and Zahedi, RP and Weis, J and Senderek, J}, title = {HNRNPA1 de novo Variant Associated with Early Childhood Onset, Rapidly Progressive Generalized Myopathy.}, journal = {Journal of neuromuscular diseases}, volume = {11}, number = {5}, pages = {1131-1137}, pmid = {39121134}, issn = {2214-3602}, mesh = {Humans ; Female ; *Heterogeneous Nuclear Ribonucleoprotein A1/genetics ; *Muscular Diseases/genetics ; Disease Progression ; Age of Onset ; Muscle, Skeletal/pathology ; Phenotype ; Mutation ; Child ; }, abstract = {HNRNPA1 variants are known to cause degenerative motoneuron and muscle diseases which manifests in middle age or later. We report on a girl with early childhood onset, rapidly progressive generalized myopathy including ultrastructural findings in line with a proteinopathy. Proteomics of patient-derived muscle and combined screening of genomic data for copy number variations identified a HNRNPA1 de novo intragenic deletion as causative for the phenotype. Our report expands the spectrum of HNRNPA1-related diseases towards early-childhood onset and adds HNRNPA1 to the growing list of ALS and myopathy genes for which certain mutations may cause severe pediatric phenotypes.}, } @article {pmid39120329, year = {2024}, author = {Steffke, C and Agarwal, S and Kabashi, E and Catanese, A}, title = {Overexpression of Toxic Poly(Glycine-Alanine) Aggregates in Primary Neuronal Cultures Induces Time-Dependent Autophagic and Synaptic Alterations but Subtle Activity Impairments.}, journal = {Cells}, volume = {13}, number = {15}, pages = {}, pmid = {39120329}, issn = {2073-4409}, mesh = {*Autophagy ; *Neurons/metabolism ; Animals ; *Synapses/metabolism ; *C9orf72 Protein/genetics/metabolism ; Cells, Cultured ; Peptides/metabolism ; Humans ; Protein Aggregates ; }, abstract = {The pathogenic expansion of the intronic GGGGCC hexanucleotide located in the non-coding region of the C9orf72 gene represents the most frequent genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). This mutation leads to the accumulation of toxic RNA foci and dipeptide repeats (DPRs), as well as reduced levels of the C9orf72 protein. Thus, both gain and loss of function are coexisting pathogenic aspects linked to C9orf72-ALS/FTD. Synaptic alterations have been largely described in C9orf72 models, but it is still not clear which aspect of the pathology mostly contributes to these impairments. To address this question, we investigated the dynamic changes occurring over time at the synapse upon accumulation of poly(GA), the most abundant DPR. Overexpression of this toxic form induced a drastic loss of synaptic proteins in primary neuron cultures, anticipating autophagic defects. Surprisingly, the dramatic impairment characterizing the synaptic proteome was not fully matched by changes in network properties. In fact, high-density multi-electrode array analysis highlighted only minor reductions in the spike number and firing rate of poly(GA) neurons. Our data show that the toxic gain of function linked to C9orf72 affects the synaptic proteome but exerts only minor effects on the network activity.}, } @article {pmid39119557, year = {2024}, author = {Fogarty, MJ and Drieberg-Thompson, JR and Bellingham, MC and Noakes, PG}, title = {Timeline of hypoglossal motor neuron death and intrinsic tongue muscle denervation in high-copy number SOD1[G93A] mice.}, journal = {Frontiers in neurology}, volume = {15}, number = {}, pages = {1422943}, pmid = {39119557}, issn = {1664-2295}, support = {R01 AG086136/AG/NIA NIH HHS/United States ; R56 HL166204/HL/NHLBI NIH HHS/United States ; }, abstract = {In amyotrophic lateral sclerosis (ALS) postmortem tissue and the SOD1 mouse model at mid-disease, death of hypoglossal motor neurons (XII MNs) is evident. These XII MNs innervate the intrinsic and extrinsic tongue muscles, and despite their importance in many oral and lingual motor behaviours that are affected by ALS (e.g., swallowing, speech, and respiratory functions), little is known about the timing and extent of tongue muscle denervation. Here in the well-characterised SOD1[G93A] (high-copy) mouse model, we evaluated XII MN numbers and intrinsic tongue muscle innervation using standard histopathological approaches, which included stereological evaluation of Nissl-stained brainstem, and the presynaptic and postsynaptic evaluation of neuromuscular junctions (NMJs), using synapsin, neurofilament, and α-bungarotoxin immunolabelling, at presymptomatic, onset, mid-disease, and endstage timepoints. We found that reduction in XII MN size at onset preceded reduced XII MN survival, while the denervation of tongue muscle did not appear until the endstage. Our study suggests that denervation-induced weakness may not be the most pertinent feature of orolingual deficits in ALS. Efforts to preserve oral and respiratory functions of XII MNs are incredibly important if we are to influence patient outcomes.}, } @article {pmid39119436, year = {2024}, author = {Galeazzi, L and Holzman, J and Porporatti, A and Rochefort, J}, title = {Lingual Fasciculation as a Point of Call for the Diagnosis of Amyotrophic Lateral Sclerosis: A Literature Review.}, journal = {Cureus}, volume = {16}, number = {7}, pages = {e64153}, pmid = {39119436}, issn = {2168-8184}, abstract = {BACKGROUND AND AIM: Dental surgeons often play a pivotal role in the initial detection of lingual fasciculations (LFs). These involuntary micro-movements of the tongue can serve as early clinical indicators of neurodegenerative diseases, with amyotrophic lateral sclerosis (ALS) being the most concerning. Therefore, it is imperative to educate dental surgeons on identifying LF and understanding the potential underlying pathologies.

OBJECTIVES: This study aimed to pinpoint the pathologies in which LFs could emerge as an early clinical marker. Our review focused on articles delineating patient populations exhibiting LF within broader pathological contexts, encompassing neurological and other conditions, with the aim of elucidating their etiologies.

METHODS: We conducted a comprehensive literature review across four databases (PubMed, Embase, Web of Science, and Scopus). Two authors independently extracted data, with consultation from a third author when necessary. Eligible articles included those describing patients with LFs, detailing the methods of detection, diagnosis, and associated pathologies.

RESULTS: Our review identified 22 articles encompassing 153 patients with LF, with an average age of 45.8 years and a female prevalence of 43%. Electromyography and ultrasound emerged as the predominant detection methods. ALS constituted the primary diagnosis in the majority of cases (91%). Additionally, other conditions diagnosed included Machado-Joseph disease (0.046%), familial transthyretin amyloid neuropathy (0.013%), Brown-Vialetto-Van-Laere syndrome (0.006%), chronic inflammatory demyelinating polyneuropathy (0.006%), bulbospinal amyotrophy or Kennedy's disease (0.006%), and osmotic demyelination syndrome (0.006%). LF secondary to organophosphate poisoning was also documented. Symptoms associated with LF encompassed taste alterations, dysphagia, difficulty swallowing, and slurred speech.

CONCLUSION: While primarily indicative of ALS, LFs may also signal diverse underlying pathologies. Healthcare practitioners should be vigilant in their detection and expedite patient referrals to facilitate early integration into care protocols.}, } @article {pmid39119372, year = {2024}, author = {Maristany, AJ and Sa, BC and Murray, C and Subramaniam, AB and Oldak, SE}, title = {Psychiatric Manifestations of Neurological Diseases: A Narrative Review.}, journal = {Cureus}, volume = {16}, number = {7}, pages = {e64152}, pmid = {39119372}, issn = {2168-8184}, abstract = {Neurological diseases often manifest with psychiatric symptoms, profoundly impacting patients' well-being and treatment outcomes. This comprehensive review examines the psychiatric manifestations associated with Alzheimer's disease, frontotemporal dementia (FTD), Parkinson's disease, multiple sclerosis (MS), stroke, epilepsy, Huntington's disease, amyotrophic lateral sclerosis (ALS), traumatic brain injury (TBI), and multiple system atrophy (MSA). Key psychiatric symptoms include agitation, depression, anxiety, apathy, hallucinations, impulsivity, and aggression across these diseases. In addition, ethical considerations in treating these symptoms are paramount, particularly regarding genetic testing implications, end-of-life discussions, informed consent, and equitable access to innovative treatments. Effective management necessitates interdisciplinary collaboration, personalized interventions, and a focus on patient autonomy. Understanding the psychiatric burden of neurological diseases is crucial for enhancing patients' quality of life. Further research is needed to elucidate underlying mechanisms and develop targeted interventions. This review underscores the importance of comprehensive assessment and ethical treatment practices to address psychiatric manifestations effectively.}, } @article {pmid39118204, year = {2024}, author = {Fang, SY and Tsai, PC and Jih, KY and Hsu, FC and Liao, YC and Yang, CC and Lee, YC}, title = {TBK1 p.Y153Qfs*9 variant may be associated with young-onset, rapidly progressive amyotrophic lateral sclerosis through a haploinsufficiency mechanism.}, journal = {Journal of the Chinese Medical Association : JCMA}, volume = {87}, number = {10}, pages = {920-926}, doi = {10.1097/JCMA.0000000000001147}, pmid = {39118204}, issn = {1728-7731}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics ; Male ; *Protein Serine-Threonine Kinases/genetics ; Adult ; *Haploinsufficiency ; *Age of Onset ; Disease Progression ; }, abstract = {BACKGROUND: TBK1 variants have been implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia spectrum disorder. The current study elucidated the clinical and molecular genetic features of a novel TBK1 variant identified in a patient with young-onset, rapidly progressive ALS.

METHODS: The coding regions of TBK1 , SOD1 , TARDBP , and FUS were genetically analyzed using Sanger sequencing. Repeat-primed polymerase chain reaction (PCR) was used to survey the GGGGCC repeat in C9ORF72 . The study participant underwent a comprehensive clinical evaluation. The functional effects of the TBK1 variant were analyzed through in vitro transfection studies.

RESULTS: We identified a novel frameshift truncating TBK1 variant, c.456_457delGT (p.Y153Qfs*9), in a man with ALS. The disease initially manifested as right hand weakness at the age of 39 years but progressed rapidly, with the revised ALS Functional Rating Scale score declining at an average monthly rate of 1.92 points in the first year after diagnosis. The patient had no cognitive dysfunction. However, Technetium-99m single photon emission tomography indicated hypoperfusion in his bilateral superior and middle frontal cortices. In vitro studies revealed that the p.Y153Qfs*9 variant resulted in a truncated TBK1 protein product, reduced TBK1 protein expression, loss of kinase function, reduced interaction with optineurin, and impaired dimerization.

CONCLUSION: The heterozygous TBK1 p.Y153Qfs*9 variant may be associated with young-onset, rapidly progressive ALS through a haploinsufficiency mechanism.}, } @article {pmid39117623, year = {2024}, author = {Hale, OJ and Wells, TR and Mead, RJ and Cooper, HJ}, title = {Mass spectrometry imaging of SOD1 protein-metal complexes in SOD1G93A transgenic mice implicates demetalation with pathology.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {6518}, pmid = {39117623}, issn = {2041-1723}, support = {EP/S002979/1//RCUK | Engineering and Physical Sciences Research Council (EPSRC)/ ; EP/S002979/1//RCUK | Engineering and Physical Sciences Research Council (EPSRC)/ ; BB/S019456/1//RCUK | Biotechnology and Biological Sciences Research Council (BBSRC)/ ; }, mesh = {Animals ; *Mice, Transgenic ; *Superoxide Dismutase-1/genetics/metabolism/chemistry ; *Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology ; Mice ; *Spinal Cord/metabolism/pathology ; *Mass Spectrometry/methods ; *Brain/metabolism/diagnostic imaging/pathology ; Copper/metabolism ; Zinc/metabolism ; Humans ; Superoxide Dismutase/metabolism/genetics/chemistry ; Mutation ; Protein Processing, Post-Translational ; Protein Multimerization ; Disease Models, Animal ; Male ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is characterized by degeneration of motor neurons in the central nervous system (CNS). Mutations in the metalloenzyme SOD1 are associated with inherited forms of ALS and cause a toxic gain of function thought to be mediated by dimer destabilization and misfolding. SOD1 binds two Cu and two Zn ions in its homodimeric form. We have applied native ambient mass spectrometry imaging to visualize the spatial distributions of intact metal-bound SOD1[G93A] complexes in SOD1[G93A] transgenic mouse spinal cord and brain sections and evaluated them against disease pathology. The molecular specificity of our approach reveals that metal-deficient SOD1[G93A] species are abundant in CNS structures correlating with ALS pathology whereas fully metalated SOD1[G93A] species are homogenously distributed. Monomer abundance did not correlate with pathology. We also show that the dimer-destabilizing post-translational modification, glutathionylation, has limited influence on the spatial distribution of SOD1 dimers.}, } @article {pmid39117616, year = {2024}, author = {Ramzan, F and Kumar, A and Abrar, F and Gray, RAV and Campbell, ZE and Liao, LMQ and Dang, A and Akanni, O and Guyn, C and Martin, DDO}, title = {Fatty links between multisystem proteinopathy and small VCP-interacting protein.}, journal = {Cell death discovery}, volume = {10}, number = {1}, pages = {358}, pmid = {39117616}, issn = {2058-7716}, abstract = {Multisystem proteinopathy (MSP) is a rare, dominantly inherited disorder that includes a cluster of diseases, including frontotemporal dementia, inclusion body myopathy, and Paget's disease of bone. MSP is caused by mutations in the gene encoding valosin-containing protein (VCP). Patients with the same mutation, even within the same family, can present with a different combination of any or all of the above diseases, along with amyotrophic lateral sclerosis (ALS). The pleiotropic effects may be linked to the greater than 50 VCP co-factors that direct VCP's many roles in the cell. Small VCP-interacting protein (SVIP) is a small protein that directs VCP to autophagosomes and lysosomes. We found that SVIP directs VCP localization to lysosomes in an acylation-dependent manner. We demonstrate that SVIP is myristoylated at Glycine 2 and palmitoylated at Cysteines 4 and 7. Acylation of SVIP is required to mediate cell death in the presence of the MSP-associated VCP variant (R155H-VCP), whereas blocking SVIP myristoylation prevents cytotoxicity. Therefore, SVIP acylation may present a novel target in MSP.}, } @article {pmid39117455, year = {2024}, author = {Lam, AYW and Tsuboyama, K and Tadakuma, H and Tomari, Y}, title = {DNAJA2 and Hero11 mediate similar conformational extension and aggregation suppression of TDP-43.}, journal = {RNA (New York, N.Y.)}, volume = {30}, number = {11}, pages = {1422-1436}, pmid = {39117455}, issn = {1469-9001}, mesh = {Humans ; Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology ; *DNA-Binding Proteins/metabolism/chemistry/genetics ; Fluorescence Resonance Energy Transfer ; Molecular Chaperones/metabolism/chemistry/genetics ; Protein Aggregates ; Protein Aggregation, Pathological/genetics/metabolism ; Protein Conformation ; RNA-Binding Proteins/metabolism/genetics/chemistry ; Chromosomal Proteins, Non-Histone/genetics ; }, abstract = {Many RNA-binding proteins (RBPs) contain low-complexity domains (LCDs) with prion-like compositions. These long intrinsically disordered regions regulate their solubility, contributing to their physiological roles in RNA processing and organization. However, this also makes these RBPs prone to pathological misfolding and aggregation that are characteristic of neurodegenerative diseases. For example, TAR DNA-binding protein 43 (TDP-43) forms pathological aggregates associated with amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). While molecular chaperones are well-known suppressors of these aberrant events, we recently reported that highly disordered, hydrophilic, and charged heat-resistant obscure (Hero) proteins may have similar effects. Specifically, Hero proteins can maintain the activity of other proteins from denaturing conditions in vitro, while their overexpression can suppress cellular aggregation and toxicity associated with aggregation-prone proteins. However, it is unclear how these protective effects are achieved. Here, we used single-molecule FRET to monitor the conformations of the aggregation-prone prion-like LCD of TDP-43. While we observed high conformational heterogeneity in wild-type LCD, the ALS-associated mutation A315T promoted collapsed conformations. In contrast, an Hsp40 chaperone, DNAJA2, and a Hero protein, Hero11, stabilized extended states of the LCD, consistent with their ability to suppress the aggregation of TDP-43. Our results link single-molecule effects on conformation to macro effects on bulk aggregation, where a Hero protein, like a chaperone, can maintain the conformational integrity of a client protein to prevent its aggregation.}, } @article {pmid39117043, year = {2024}, author = {Curtisi, J and Ellis-Wittenhagen, J and Kokanovich, T and Volk-Craft, B}, title = {Compassionate Ventilator Release in Patients With Neuromuscular Disease: A Two-Case Comparison.}, journal = {Journal of pain and symptom management}, volume = {68}, number = {5}, pages = {e392-e396}, doi = {10.1016/j.jpainsymman.2024.07.028}, pmid = {39117043}, issn = {1873-6513}, mesh = {Humans ; Amyotrophic Lateral Sclerosis/complications/therapy ; Dyspnea/therapy/etiology ; Myasthenia Gravis/therapy/complications ; Neuromuscular Diseases/complications/therapy ; *Respiration, Artificial ; Terminal Care ; Ventilator Weaning ; }, abstract = {Dyspnea, the subjective sensation of breathlessness, is a distressing and potentially traumatic symptom. Dyspnea associated with mechanical ventilation may contribute to intensive care unit (ICU) associated post-traumatic stress disorder and impaired quality of life. Dyspnea is both difficult to alleviate and a cause of significant distress to patients, their loved ones, and care providers People living with neuromuscular disease, such as amyotrophic lateral sclerosis (ALS) or myasthenia gravis (MG), often rely on a ventilator at late stages of illness due to complications of progressive respiratory muscle weakness and paralysis. When unable to wean from the ventilator, conversations turn towards goals of care and release from the ventilator for comfort and end of life (EOL). Patients with and without neuromuscular disease have high risk for dyspnea at EOL upon ventilator liberation. Although limited recommendations have been published specific to patients with ALS, no guidelines currently exist for the terminal liberation from mechanical ventilation in patients experiencing respiratory muscle insufficiency from a neuromuscular disease. Further research on this topic is needed, including creation of a protocol for ventilator release in patients with neuromuscular disease. The following case reports detail the dissimilar EOL experiences of two patients with different forms of neuromuscular disease.}, } @article {pmid39116956, year = {2024}, author = {Yang, N and Shi, L and Xu, P and Ren, F and Li, C and Qi, X}, title = {Identification of potential drug targets for amyotrophic lateral sclerosis by Mendelian randomization analysis based on brain and plasma proteomics.}, journal = {Experimental gerontology}, volume = {195}, number = {}, pages = {112538}, doi = {10.1016/j.exger.2024.112538}, pmid = {39116956}, issn = {1873-6815}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/blood/drug therapy ; *Mendelian Randomization Analysis ; *Genome-Wide Association Study ; *Proteomics/methods ; *Brain/metabolism ; *Protein Interaction Maps ; Anoctamins/genetics ; Bayes Theorem ; Blood Proteins/analysis/metabolism ; Genetic Predisposition to Disease ; }, abstract = {Amyotrophic lateral sclerosis as a fatal neurodegenerative disease currently lacks effective therapeutic agents. Thus, finding new therapeutic targets to drive disease treatment is necessary. In this study, we utilized brain and plasma proteins as genetic instruments obtained from genome-wide association studies to conduct a Mendelian randomization analysis to identify potential drug targets for amyotrophic lateral sclerosis. Additionally, we validated our results externally using other datasets. We also used Bayesian co-localization analysis and phenotype scanning. Furthermore, we constructed a protein-protein interaction network to elucidate potential correlations between the identified proteins and existing targets. Mendelian randomization analysis indicated that elevated levels of ANO5 (OR = 1.30; 95 % CI, 1.14-1.49; P = 1.52E-04), SCFD1 (OR = 3.82; 95 % CI, 2.39-6.10; P = 2.19E-08), and SIGLEC9 (OR = 1.05; 95% CI, 1.03-1.07; P = 4.71E-05) are associated with an increased risk of amyotrophic lateral sclerosis, with external validation supporting these findings. Co-localization analysis confirmed that ANO5, SCFD1, and SIGLEC9 (coloc.abf-PPH4 = 0.848, 0.984, and 0.945, respectively) shared the same variant with amyotrophic lateral sclerosis, further substantiating potential role of these proteins as a therapeutic target. There are interactive relationships between the potential proteins and existing targets of amyotrophic lateral sclerosis. Our findings suggested that elevated levels of ANO5, SCFD1, and SIGLEC9 are connected with an increased risk of amyotrophic lateral sclerosis and might be promising therapeutic targets. However, further exploration is necessary to fully understand the underlying mechanisms involved.}, } @article {pmid39116527, year = {2024}, author = {Ceron-Codorniu, M and Torres, P and Fernàndez-Bernal, A and Rico-Rios, S and Serrano, JC and Miralles, MP and Beltran, M and Garcera, A and Soler, RM and Pamplona, R and Portero-Otín, M}, title = {TDP-43 dysfunction leads to bioenergetic failure and lipid metabolic rewiring in human cells.}, journal = {Redox biology}, volume = {75}, number = {}, pages = {103301}, pmid = {39116527}, issn = {2213-2317}, mesh = {Humans ; *Energy Metabolism ; *DNA-Binding Proteins/metabolism/genetics ; *Lipid Metabolism ; HeLa Cells ; *Adenosine Triphosphate/metabolism ; Induced Pluripotent Stem Cells/metabolism/cytology ; Coenzyme A Ligases/metabolism/genetics ; Motor Neurons/metabolism/pathology ; Cell Survival ; Oxygen Consumption ; Ferroptosis ; Long-Chain-Fatty-Acid-CoA Ligase ; }, abstract = {The dysfunction of TAR DNA-binding protein 43 (TDP-43) is implicated in various neurodegenerative diseases, though the specific contributions of its toxic gain-of-function versus loss-of-function effects remain unclear. This study investigates the impact of TARDBP loss on cellular metabolism and viability using human-induced pluripotent stem cell-derived motor neurons and HeLa cells. TARDBP silencing led to reduced metabolic activity and cell growth, accompanied by neurite degeneration and decreased oxygen consumption rates in both cell types. Notably, TARDBP depletion induced a metabolic shift, impairing ATP production, increasing metabolic inflexibility, and elevating free radical production, indicating a critical role for TDP-43 in maintaining cellular bioenergetics. Furthermore, TARDBP loss triggered non-apoptotic cell death, increased ACSL4 expression, and reprogrammed lipid metabolism towards lipid droplet accumulation, while paradoxically enhancing resilience to ferroptosis inducers. Overall, our findings highlight those essential cellular traits such as ATP production, metabolic activity, oxygen consumption, and cell survival are highly dependent on TARDBP function.}, } @article {pmid39116263, year = {2024}, author = {Aguilar-Vázquez, CA and Aguilar-Castillo, SJ and Raymundo-Carrillo, AD}, title = {[Electrodiagnostic support in an atypical form of amyotrophic lateral sclerosis (Vulpian-Bernhardt syndrome)].}, journal = {Revista medica del Instituto Mexicano del Seguro Social}, volume = {62}, number = {1}, pages = {1-8}, pmid = {39116263}, issn = {2448-5667}, mesh = {Humans ; Male ; *Amyotrophic Lateral Sclerosis/diagnosis/mortality/therapy ; *Electrodiagnosis/methods ; }, abstract = {BACKGROUND: Vulpian-Bernhardt syndrome is an atypical form of the motor neuron disease described since the 19th century. The importance of a timely diagnosis lies in the increased survival present in this variant. Due to the clinical rarity and complex diagnosis we report a clinical case of this disease, which is why we describe the typical clinical presentation, the diagnostic approach, and we make a bibliographic review of this neurodegenerative disorder as well.

CLINICAL CASE: Latin American man whose clinical case onset was characterized by thoracic asymmetric and increasing limb weakness, showing affection from distal to proximal upper limbs area. Subsequently, symptoms worsened to the point of limiting day-to-day activities and conditioning patient's physical independence. Physical examination was consistent with motor neuron disease. Nerve conduction studies were performed and confirmed findings compatible with motor neuron involvement limited to thoracic limbs.

CONCLUSION: Vulpian-Bernhardt syndrome is an uncommon form of motor neuron disease. Due to the rarity of its presentation, it is frequent to confuse clinical profile even for trained physicians. The importance of electrodiagnosis relies in identifying the neurogenic origin of the disease, as well as the active denervation and reinnervation data. Considering that with this syndrome patients have a longer survival than with the classic form of amyotrophic lateral sclerosis, it is important to have a clear diagnosis approach in order to provide a better quality of life and supportive treatment.}, } @article {pmid39115673, year = {2025}, author = {Mishra, Y and Kumar, A and Kaundal, RK}, title = {Mitochondrial Dysfunction is a Crucial Immune Checkpoint for Neuroinflammation and Neurodegeneration: mtDAMPs in Focus.}, journal = {Molecular neurobiology}, volume = {62}, number = {6}, pages = {6715-6747}, pmid = {39115673}, issn = {1559-1182}, support = {EEQ/2021/000875//Science & Engineering Research Board (SERB), Department of Science and Technology, Govt of India/ ; }, mesh = {Humans ; Animals ; *Mitochondria/metabolism/pathology/immunology ; *Neuroinflammatory Diseases/immunology/pathology/metabolism ; *Neurodegenerative Diseases/immunology/pathology/metabolism ; Immunity, Innate ; *Nerve Degeneration/immunology/pathology ; *Inflammation/immunology/pathology ; }, abstract = {Neuroinflammation is a pivotal factor in the progression of both age-related and acute neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis, and stroke. Mitochondria, essential for neuronal health due to their roles in energy production, calcium buffering, and oxidative stress regulation, become increasingly susceptible to dysfunction under conditions of metabolic stress, aging, or injury. Impaired mitophagy in aged or injured neurons leads to the accumulation of dysfunctional mitochondria, which release mitochondrial-derived damage-associated molecular patterns (mtDAMPs). These mtDAMPs act as immune checkpoints, activating pattern recognition receptors (PRRs) and triggering innate immune signaling pathways. This activation initiates inflammatory responses in neurons and brain-resident immune cells, releasing cytokines and chemokines that damage adjacent healthy neurons and recruit peripheral immune cells, further amplifying neuroinflammation and neurodegeneration. Long-term mitochondrial dysfunction perpetuates a chronic inflammatory state, exacerbating neuronal injury and contributing additional immunogenic components to the extracellular environment. Emerging evidence highlights the critical role of mtDAMPs in initiating and sustaining neuroinflammation, with circulating levels of these molecules potentially serving as biomarkers for disease progression. This review explores the mechanisms of mtDAMP release due to mitochondrial dysfunction, their interaction with PRRs, and the subsequent activation of inflammatory pathways. We also discuss the role of mtDAMP-triggered innate immune responses in exacerbating both acute and chronic neuroinflammation and neurodegeneration. Targeting dysfunctional mitochondria and mtDAMPs with pharmacological agents presents a promising strategy for mitigating the initiation and progression of neuropathological conditions.}, } @article {pmid39115327, year = {2024}, author = {Lescouzères, L and Patten, SA}, title = {Promising animal models for amyotrophic lateral sclerosis drug discovery: a comprehensive update.}, journal = {Expert opinion on drug discovery}, volume = {19}, number = {10}, pages = {1213-1233}, doi = {10.1080/17460441.2024.2387791}, pmid = {39115327}, issn = {1746-045X}, mesh = {*Amyotrophic Lateral Sclerosis/drug therapy/physiopathology ; Animals ; Humans ; *Disease Models, Animal ; *Drug Discovery/methods ; Mice ; Genetic Therapy/methods ; Translational Research, Biomedical/methods ; Induced Pluripotent Stem Cells ; Drug Development/methods ; Caenorhabditis elegans ; Motor Neurons/drug effects ; Zebrafish ; }, abstract = {INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive loss of motor neurons. Several animal models have been generated to understand ALS pathogenesis. They have provided valuable insight into disease mechanisms and the development of therapeutic strategies.

AREAS COVERED: In this review, the authors provide a concise overview of simple genetic model organisms, including C. elegans, Drosophila, zebrafish, and mouse genetic models that have been generated to study ALS. They emphasize the benefits of each model and their application in translational research for discovering new chemicals, gene therapy approaches, and antibody-based strategies for treating ALS.

EXPERT OPINION: Significant progress is being made in identifying new therapeutic targets for ALS. This progress is being enabled by promising animal models of the disease using increasingly effective genetic and pharmacological strategies. There are still challenges to be overcome in order to achieve improved success rates for translating drugs from animal models to clinics for treating ALS. Several promising future directions include the establishment of novel preclinical protocol standards, as well as the combination of animal models with human induced pluripotent stem cells (iPSCs).}, } @article {pmid39114608, year = {2024}, author = {Koike, Y}, title = {Abnormal Splicing Events due to Loss of Nuclear Function of TDP-43: Pathophysiology and Perspectives.}, journal = {JMA journal}, volume = {7}, number = {3}, pages = {313-318}, pmid = {39114608}, issn = {2433-3298}, abstract = {Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are neurodegenerative diseases with a progressive and fatal course. They are often comorbid and share the same molecular spectrum. Their key pathological features are the formation of the aggregation of TDP-43, an RNA-binding protein, in the cytoplasm and its depletion from the nucleus in the central nervous system. In the nucleus, TDP-43 regulates several aspects of RNA metabolism, ranging from RNA transcription and alternative splicing to RNA transport. Suppressing the aberrant splicing events during RNA processing is one of the significant functions of TDP-43. This function is impaired when TDP-43 becomes depleted from the nucleus. Several critical cryptic splicing targets of TDP-43 have recently emerged, such as STMN2, UNC13A, and others. UNC13A is an important ALS/FTD risk gene, and the genetic variations, single nucleotide polymorphisms, cause disease via the increased susceptibility for cryptic exon inclusion under the TDP-43 dysfunction. Moreover, TDP-43 has an autoregulatory mechanism that regulates the splicing of its mRNA (TARDBP mRNA) in the healthy state. This study provides recent findings on the splicing regulatory function of TDP-43 and discusses the prospects of using these aberrant splicing events as efficient biomarkers.}, } @article {pmid39113924, year = {2024}, author = {Ueta, Y and Kanbayashi, T and Miyaji, Y and Hatanaka, Y and Tachiyama, K and Takahashi, K and Terashi, H and Aizawa, H and Sonoo, M}, title = {The speed of completion of the decremental responses on repetitive nerve stimulation.}, journal = {Clinical neurophysiology practice}, volume = {9}, number = {}, pages = {211-216}, pmid = {39113924}, issn = {2467-981X}, abstract = {OBJECTIVE: It is generally believed that the decremental response in repetitive nerve stimulation (RNS) stabilizes at the fourth or fifth response. We have a preliminary impression that the decremental response approaches a plateau earlier in proximal muscles than in distal muscles. We investigated the speed of the completion of the decremental response in different muscles.

METHODS: The "decrement completion ratio (DCR)" in the second or third response (DCR2 or DCR3) was defined as the ratio of the decremental percentage of the second or third response to that of the fourth response. Patients showing more than 10% decremental response both in the abductor pollicis (APB) and deltoid muscles were retrospectively extracted from our EMG database. The DCR2 and DCR3 were compared between two muscles in patients with myasthenia gravis (MG) and amyotrophic lateral sclerosis (ALS).

RESULTS: Identified subjects consisted of 11patients with MG and 11 patients with ALS. Multiple regression analysis revealed that only the difference of muscle influenced on DCR2 and DCR3, with no contribution from the different disorder (MG or ALS) or the initial amplitude of the compound muscle action potential (CMAP). Both DCR2 and DCR3 were significantly higher in deltoid than in APB. In ALS, the normalized CMAP amplitude was not different between APB and deltoid whereas the decremental percentage was significantly higher in deltoid, suggesting a lower safety factor of the neuromuscular transmission in proximal muscles.

CONCLUSIONS: The decremental response completed more rapidly in deltoid than in APB which may be related to the lower safety factor also documented by this study.

SIGNIFICANCE: Unexpected early completion of the decrement such as at the second response in RNS is not a technical error but may be an extreme of the rapid completion in deltoid, a proximal muscle.}, } @article {pmid39113457, year = {2024}, author = {Pervushina, EV and Kutlubaev, MA and Saifullina, EV and Gaisina, EV and Smakova, LA and Khidiyatova, IM}, title = {[Amyotrophic lateral sclerosis associated with a new pathogenic variant of the ERBB4 gene].}, journal = {Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova}, volume = {124}, number = {7}, pages = {165-168}, doi = {10.17116/jnevro2024124071165}, pmid = {39113457}, issn = {1997-7298}, mesh = {Humans ; *Receptor, ErbB-4/genetics ; *Amyotrophic Lateral Sclerosis/genetics ; Mutation ; Male ; Middle Aged ; Disease Progression ; Female ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a sporadic disease in most of the cases; in 10-15% of cases genetic forms are recorded. A genetic form of ALS associated with the mutation in the ERBB4 gene (ALS19) has been reported in 2013. A protein encoded by the ERBB4 is probably involved in ubiquitous component of the pathogenesis of ALS. We present a case of ALS associated with a new pathogenic variant of the ERBB4 gene, with early bulbar onset and slow progression of the disease within 10 years.}, } @article {pmid39113334, year = {2024}, author = {Khadilkar, V and Lad, S and Mondkar, S and Yewale, S and Dange, N and Wagle, S and Khadilkar, A}, title = {Pediatric Advanced Life Support Tape for Indian Children.}, journal = {Indian pediatrics}, volume = {61}, number = {10}, pages = {961-965}, pmid = {39113334}, issn = {0974-7559}, mesh = {Humans ; India ; Male ; Female ; Child, Preschool ; Child ; *Body Height ; *Body Weight ; *Anthropometry/instrumentation ; Reproducibility of Results ; }, abstract = {OBJECTIVE: To design a specific advanced life support (ALS) tape based on recent Indian multicenter height/length and weight data to accurately estimate the weight from the recumbent length.

METHODS: We designed the new ALS tape by matching the median weights to median heights/lengths from the recently published Indian multicenter growth data, maintaining the same color codes as the Broselow tape. The accuracy of weight estimation for the newly designed ALS tape was validated and compared with the Broselow estimated weights at a tertiary care hospital.

RESULTS: The color (weight) band matched median heights (cm) from the new ALS tape were higher (53.0 vs 53.9 for grey, 63.1 vs 67.4 for pink, 70.6 vs 76.4 for red, 79 vs 85.5 for purple, 89.6 vs 95.5 for yellow, 101.9 vs 107.5 for white, 126.1 vs 130.5 for orange and 137 vs 140.5 for green) than the Broselow tape. For every color band on the newly designed ALS tape, a sizable proportion of children (27% for grey, 78% for pink, 83% for red, 38% for purple, 63% for yellow, 41% for white, 35% for blue, 54% for orange) recorded a higher Broselow color band, suggesting overestimated weights at each color band. The percentage difference in the estimated weight from the actual weight was very small (-0.5% for under-5 years and 0.2% for older children) using the new ALS tape as compared to Broselow tape.

CONCLUSION: This Indianized ALS tape estimated Indian children's weights more accurately. Use of the newly designed ALS tape may reduce the errors in calculating emergency medications, fluids and equipment sizes. Further studies are required to validate this tape in pediatric emergency departments in India.}, } @article {pmid39112530, year = {2024}, author = {Tu, S and Li, T and Carroll, AS and Mahoney, CJ and Huynh, W and Park, SB and Henderson, R and Vucic, S and Kiernan, MC and Lin, CS}, title = {Central neurodegeneration in Kennedy's disease accompanies peripheral motor dysfunction.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {18331}, pmid = {39112530}, issn = {2045-2322}, mesh = {Humans ; Male ; Middle Aged ; Female ; Aged ; *Bulbo-Spinal Atrophy, X-Linked/physiopathology/pathology ; Adult ; Amyotrophic Lateral Sclerosis/physiopathology/pathology/diagnostic imaging ; Brain/diagnostic imaging/pathology/physiopathology ; Magnetic Resonance Imaging ; White Matter/diagnostic imaging/pathology/physiopathology ; }, abstract = {Spinal and bulbar muscular atrophy (SBMA), or Kennedy's disease (KD), is a rare hereditary neuromuscular disorder demonstrating commonalities with amyotrophic lateral sclerosis (ALS). The current study aimed to define functional and central nervous system abnormalities associated with SBMA pathology, their interaction, and to identify novel clinical markers for quantifying disease activity. 27 study participants (12 SBMA; 8 ALS; 7 Control) were recruited. SBMA patients underwent comprehensive motor and sensory functional assessments, and neurophysiological testing. All participants underwent whole-brain structural and diffusion MRI. SBMA patients demonstrated marked peripheral motor and sensory abnormalities across clinical assessments. Increased abnormalities on neurological examination were significantly associated with increased disease duration in SBMA patients (R[2] = 0.85, p < 0.01). Widespread juxtacortical axonal degeneration of corticospinal white matter tracts were detected in SBMA patients (premotor; motor; somatosensory; p < 0.05), relative to controls. Increased axial diffusivity was significantly correlated with total neuropathy score in SBMA patients across left premotor (R[2] = 0.59, p < 0.01), motor (R[2] = 0.63, p < 0.01), and somatosensory (R[2] = 0.61, p < 0.01) tracts. The present series has identified involvement of motor and sensory brain regions in SBMA, associated with disease duration and increasing severity of peripheral neuropathy. Quantification of annualized brain MRI together with Total Neuropathy Score may represent a novel approach for clinical monitoring.}, } @article {pmid39111585, year = {2024}, author = {Bischoff, KE and Liera, D and Tang, J and Madugala, N and Cohen, E and Galea, MD and Lindenberger, E and Pantilat, SZ and Lomen-Hoerth, C}, title = {Development and Piloting of a Bereaved Care Partner Survey to Inform Quality Improvement in ALS Supportive Care.}, journal = {Journal of pain and symptom management}, volume = {68}, number = {5}, pages = {467-476.e2}, doi = {10.1016/j.jpainsymman.2024.07.031}, pmid = {39111585}, issn = {1873-6513}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy ; *Quality Improvement ; Pilot Projects ; *Bereavement ; Female ; Male ; *Palliative Care ; Caregivers ; Middle Aged ; Aged ; Surveys and Questionnaires ; Adult ; }, abstract = {OBJECTIVES: Bereaved care partner surveys typically focus on the experience with care in the final days of life. We sought to develop and pilot a novel bereaved care partner survey to understand experiences with ALS supportive care provided throughout the illness and identify opportunities for quality improvement.

METHODS: We developed the survey using a multisite, interdisciplinary consensus process involving ALS and palliative care clinicians as well as patient advocates. We then piloted the survey at a single site via video interviews with care partners of patients who died from ALS between three and 15 months prior. Qualitative findings were analyzed using Rapid Qualitative Analysis.

RESULTS: The survey includes 17 core questions and nine demographic items. Questions inquire about whether the patient and care partner received adequate help with physical symptoms, emotional and practical needs, education about the illness and how to provide hands-on care, preparing for what was to come, and bereavement. They also query whether care was person-centered and consistent with the patient's values and preferences. During the pilot with 18 bereaved care partners, the tool generated detailed feedback about aspects of care to preserve as well as how to improve ALS supportive care.

DISCUSSION: We developed and piloted a bereaved care partner survey to understand and improve the quality of ALS supportive care, which was found to be feasible and acceptable. Next steps include testing it at additional centers in order to generate learnings that can advance ALS supportive care in ways that are meaningful to patients and care partners.}, } @article {pmid39111522, year = {2024}, author = {Li, Q and Zhu, W and Wen, X and Zang, Z and Da, Y and Lu, J}, title = {Different baseline functional patterns of the frontal cortex in amyotrophic lateral sclerosis patients with Corticospinal tract hyperintensity.}, journal = {Brain research}, volume = {1844}, number = {}, pages = {149140}, doi = {10.1016/j.brainres.2024.149140}, pmid = {39111522}, issn = {1872-6240}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology/diagnostic imaging ; Male ; Female ; *Pyramidal Tracts/physiopathology/diagnostic imaging ; Middle Aged ; *Magnetic Resonance Imaging/methods ; *Frontal Lobe/physiopathology/diagnostic imaging ; Aged ; Adult ; Brain Mapping/methods ; }, abstract = {Nearly half of the amyotrophic lateral sclerosis (ALS) patients showed hyperintensity of the corticospinal tract (CST+), yet whether brain functional pattern differs between CST+and CST- patients remains obscure. In the current study, 19 ALS CST+, 41 ALS CST- patients and 37 healthy controls (HC) underwent resting state fMRI scans. We estimated local activity and connectivity patterns via the Amplitude of Low Frequency Fluctuations (ALFF) and the Network-Based Statistic (NBS) approaches respectively. The ALS CST+patients did not differ from the CST- patients in amyotrophic lateral sclerosis functional rating scale revised (ALSFRS-R) score and disease duration. ALFF of the superior frontal gyrus (SFG) and the inferior frontal gyrus pars opercularis (OIFG) were highest in the HC and lowest in the ALS CST- patients, resulting in significant group differences (PFWE<0.05). NBS analysis revealed a frontal network consisting of connections between SFG, OIFG, orbital frontal gyrus, middle cingulate cortex and the basal ganglia, which exhibited HC>ALS CST+ > ALS CST- group differences (PFWE=0.037) as well. The ALFF of the OIFG was significantly correlated with ALSFRS-R (R=0.34, P=0.028) and mean connectivity of the frontal network was trend-wise significantly correlated with disease duration (R=-0.31, P=0.052) in the ALS CST- patients. However, these correlations were insignificant in ALS CST+patients (P values > 0.8). In conclusion, The ALS CST+patients exhibited different patterns of baseline functional activity and connectivity in the frontal cortex which may indicate a functional compensatory effect.}, } @article {pmid39111227, year = {2024}, author = {Torghabeh, FA and Moghadam, EA and Hosseini, SA}, title = {Simultaneous time-frequency analysis of gait signals of both legs in classifying neurodegenerative diseases.}, journal = {Gait & posture}, volume = {113}, number = {}, pages = {443-451}, doi = {10.1016/j.gaitpost.2024.07.302}, pmid = {39111227}, issn = {1879-2219}, mesh = {Humans ; *Neurodegenerative Diseases/diagnosis/physiopathology ; *Gait Analysis/methods ; Gait Disorders, Neurologic/classification/diagnosis/physiopathology/etiology ; Amyotrophic Lateral Sclerosis/diagnosis/physiopathology/classification ; Wavelet Analysis ; Male ; Female ; Middle Aged ; Parkinson Disease/diagnosis/physiopathology/classification ; Deep Learning ; Signal Processing, Computer-Assisted ; Case-Control Studies ; Huntington Disease/physiopathology/diagnosis/classification ; Aged ; }, abstract = {BACKGROUND: Neurodegenerative diseases (NDDs) pose significant challenges due to their debilitating nature and limited therapeutic options. Accurate and timely diagnosis is crucial for optimizing patient care and treatment strategies. Gait analysis, utilizing wearable sensors, has shown promise in assessing motor abnormalities associated with NDDs.

RESEARCH QUESTION: Research Question 1 To what extent can analyzing the interaction of both limbs in the time-frequency domain serve as a suitable methodology for accurately classifying NDDs? Research Question 2 How effective is the utilization of color-coded images, in conjunction with deep transfer learning models, for the classification of NDDs?

METHODS: GaitNDD database was used, comprising recordings from patients with Huntington's disease, amyotrophic lateral sclerosis, Parkinson's disease, and healthy controls. The gait signals underwent signal preparation, wavelet coherence analysis, and principal component analysis for feature enhancement. Deep transfer learning models (AlexNet, GoogLeNet, SqueezeNet) were employed for classification. Performance metrics, including accuracy, sensitivity, specificity, precision, and F1 score, were evaluated using 5-fold cross-validation.

RESULTS: The classification performance of the models varied depending on the time window used. For 5-second gait signal segments, AlexNet achieved an accuracy of 95.91 %, while GoogLeNet and SqueezeNet achieved accuracies of 96.49 % and 92.73 %, respectively. For 10-second segments, AlexNet outperformed other models with an accuracy of 99.20 %, while GoogLeNet and SqueezeNet achieved accuracies of 96.75 % and 95.00 %, respectively. Statistical tests confirmed the significance of the extracted features, indicating their discriminative power for classification.

SIGNIFICANCE: The proposed method demonstrated superior performance compared to previous studies, offering a non-invasive and cost-effective approach for the automated diagnosis of NDDs. By analyzing the interaction between both legs during walking using wavelet coherence, and utilizing deep transfer learning models, accurate classification of NDDs was achieved.}, } @article {pmid39110593, year = {2024}, author = {Hoh, KL and Mu, B and See, T and Ng, AYE and Ng, AQE and Zhang, D}, title = {VAP-mediated membrane-tethering mechanisms implicate ER-PM contact function in pH homeostasis.}, journal = {Cell reports}, volume = {43}, number = {8}, pages = {114592}, doi = {10.1016/j.celrep.2024.114592}, pmid = {39110593}, issn = {2211-1247}, mesh = {*Endoplasmic Reticulum/metabolism ; Hydrogen-Ion Concentration ; *Homeostasis ; *Cell Membrane/metabolism ; Humans ; *Schizosaccharomyces/metabolism ; Schizosaccharomyces pombe Proteins/metabolism ; Vesicular Transport Proteins/metabolism/genetics ; Protein Binding ; Membrane Proteins/metabolism ; Phospholipids/metabolism ; Mutation ; Amyotrophic Lateral Sclerosis/metabolism ; }, abstract = {Vesicle-associated membrane protein (VAMP)-associated proteins (VAPs) are highly conserved endoplasmic reticulum (ER)-resident proteins that establish ER contacts with multiple membrane compartments in many eukaryotes. However, VAP-mediated membrane-tethering mechanisms remain ambiguous. Here, focusing on fission yeast ER-plasma membrane (PM) contact formation, using systematic interactome analyses and quantitative microscopy, we predict a non-VAP-protein direct binding-based ER-PM coupling. We further reveal that VAP-anionic phospholipid interactions may underlie ER-PM association and define the pH-responsive nature of VAP-tethered membrane contacts. Such conserved interactions with anionic phospholipids are generally defective in amyotrophic lateral sclerosis-associated human VAPB mutant. Moreover, we identify a conserved FFAT-like motif locating at the autoinhibitory hotspot of the essential PM proton pump Pma1. This modulatory VAP-Pma1 interaction appears crucial for pH homeostasis. We thus propose an ingenious strategy for maintaining intracellular pH by coupling Pma1 modulation with pH-sensory ER-PM contacts via VAP-mediated interactions.}, } @article {pmid39108340, year = {2024}, author = {Tröger, J and Dörr, F and Schwed, L and Linz, N and König, A and Thies, T and Barbe, MT and Orozco-Arroyave, JR and Rusz, J}, title = {An automatic measure for speech intelligibility in dysarthrias-validation across multiple languages and neurological disorders.}, journal = {Frontiers in digital health}, volume = {6}, number = {}, pages = {1440986}, pmid = {39108340}, issn = {2673-253X}, abstract = {INTRODUCTION: Dysarthria, a motor speech disorder caused by muscle weakness or paralysis, severely impacts speech intelligibility and quality of life. The condition is prevalent in motor speech disorders such as Parkinson's disease (PD), atypical parkinsonism such as progressive supranuclear palsy (PSP), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS). Improving intelligibility is not only an outcome that matters to patients but can also play a critical role as an endpoint in clinical research and drug development. This study validates a digital measure for speech intelligibility, the ki: SB-M intelligibility score, across various motor speech disorders and languages following the Digital Medicine Society (DiMe) V3 framework.

METHODS: The study used four datasets: healthy controls (HCs) and patients with PD, HD, PSP, and ALS from Czech, Colombian, and German populations. Participants' speech intelligibility was assessed using the ki: SB-M intelligibility score, which is derived from automatic speech recognition (ASR) systems. Verification with inter-ASR reliability and temporal consistency, analytical validation with correlations to gold standard clinical dysarthria scores in each disease, and clinical validation with group comparisons between HCs and patients were performed.

RESULTS: Verification showed good to excellent inter-rater reliability between ASR systems and fair to good consistency. Analytical validation revealed significant correlations between the SB-M intelligibility score and established clinical measures for speech impairments across all patient groups and languages. Clinical validation demonstrated significant differences in intelligibility scores between pathological groups and healthy controls, indicating the measure's discriminative capability.

DISCUSSION: The ki: SB-M intelligibility score is a reliable, valid, and clinically relevant tool for assessing speech intelligibility in motor speech disorders. It holds promise for improving clinical trials through automated, objective, and scalable assessments. Future studies should explore its utility in monitoring disease progression and therapeutic efficacy as well as add data from further dysarthrias to the validation.}, } @article {pmid39108272, year = {2024}, author = {De Federicis, D and Bassani, C and Chiarelli, RR and Montini, F and Giordano, A and Esposito, F and Riva, N and Quattrini, A and Martinelli, V and Filippi, M and Farina, C}, title = {Circulating MAIT cells in multiple sclerosis and amyotrophic lateral sclerosis.}, journal = {Frontiers in immunology}, volume = {15}, number = {}, pages = {1436717}, pmid = {39108272}, issn = {1664-3224}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/immunology/blood ; *Mucosal-Associated Invariant T Cells/immunology/metabolism ; Male ; Middle Aged ; Female ; Adult ; Aged ; Multiple Sclerosis/immunology/blood ; CD8-Positive T-Lymphocytes/immunology/metabolism ; Biomarkers ; Flow Cytometry ; }, abstract = {Neurological disorders, including multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS), may be associated with alterations in blood cell composition and phenotype. Here, we focused our attention on circulating mucosal-associated invariant T (MAIT) cells, a CD8[+] T cell memory population expressing the invariant Vα7.2 region in the T cell receptor and high surface levels of the CD161 marker. Transcriptomics data relative to peripheral blood mononuclear cells (PBMC) highlighted downregulation of CD161 and other MAIT-associated markers in progressive MS and not relapsing remitting (RR)-MS when gene expressions relative to each disease course were compared to those from healthy controls. Multiparametric flow cytometry of freshly isolated PBMC samples from untreated RR-MS, primary or secondary progressive MS (PP- or SP-MS), ALS and age- and sex-matched healthy controls revealed specific loss of circulating CD8[+] MAIT cells in PP-MS and no other MS courses or another neurological disorder such as ALS. Overall, these observations point to the existence of immunological changes in blood specific for the primary progressive course of MS that may support clinical definition of disease.}, } @article {pmid39107374, year = {2024}, author = {Monselise, EB and Vyazmensky, M and Scherf, T and Batushansky, A and Fishov, I}, title = {D-Glutamate production by stressed Escherichia coli gives a clue for the hypothetical induction mechanism of the ALS disease.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {18247}, pmid = {39107374}, issn = {2045-2322}, mesh = {*Amyotrophic Lateral Sclerosis/metabolism/microbiology ; *Escherichia coli/metabolism ; *Glutamic Acid/metabolism ; Humans ; Stress, Physiological ; Complement C1q/metabolism ; Nitrogen/metabolism ; Carbon/metabolism ; }, abstract = {In the search for the origin of Amyotrophic Lateral Sclerosis disease (ALS), we hypothesized earlier (Monselise, 2019) that D-amino acids produced by stressed microbiome may serve as inducers of the disease development. Many examples of D-amino acid accumulation under various stress conditions were demonstrated in prokaryotic and eukaryotic cells. In this work, wild-type Escherichia coli, members of the digestive system, were subjected to carbon and nitrogen starvation stress. Using NMR and LC-MS techniques, we found for the first time that D-glutamate accumulated in the stressed bacteria but not in control cells. These results together with the existing knowledge, allow us to suggest a new insight into the pathway of ALS development: D-glutamate, produced by the stressed microbiome, induces neurobiochemical miscommunication setting on C1q of the complement system. Proving this insight may have great importance in preventive medicine of such MND modern-age diseases as ALS, Alzheimer, and Parkinson.}, } @article {pmid39107037, year = {2025}, author = {Jang, DG and Dou, JF and Koubek, EJ and Teener, S and Zhou, L and Bakulski, KM and Mukherjee, B and Batterman, SA and Feldman, EL and Goutman, SA}, title = {Multiple metal exposures associate with higher amyotrophic lateral sclerosis risk and mortality independent of genetic risk and correlate to self-reported exposures: a case-control study.}, journal = {Journal of neurology, neurosurgery, and psychiatry}, volume = {96}, number = {4}, pages = {329-339}, doi = {10.1136/jnnp-2024-333978}, pmid = {39107037}, issn = {1468-330X}, support = {K23 ES027221/ES/NIEHS NIH HHS/United States ; P30 CA023108/CA/NCI NIH HHS/United States ; R01 NS127188/NS/NINDS NIH HHS/United States ; R01 TS000344/TS/ATSDR CDC HHS/United States ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/mortality/genetics/blood/urine ; Male ; Female ; Middle Aged ; Case-Control Studies ; Aged ; *Metals/urine/blood/adverse effects ; *Environmental Exposure/adverse effects ; Copper/urine/blood ; Polymorphism, Single Nucleotide ; Risk Factors ; Genome-Wide Association Study ; Self Report ; Adult ; Selenium/blood/urine ; Genetic Predisposition to Disease ; Zinc/urine/blood ; }, abstract = {BACKGROUND: The pathogenesis of amyotrophic lateral sclerosis (ALS) involves both genetic and environmental factors. This study investigates associations between metal measures in plasma and urine, ALS risk and survival and exposure sources.

METHODS: Participants with and without ALS from Michigan provided plasma and urine samples for metal measurement via inductively coupled plasma mass spectrometry. ORs and HRs for each metal were computed using risk and survival models. Environmental risk scores (ERS) were created to evaluate the association between exposure mixtures and ALS risk and survival and exposure source. ALS (ALS-PGS) and metal (metal-PGS) polygenic risk scores were constructed from an independent genome-wide association study and relevant literature-selected single-nucleotide polymorphisms.

RESULTS: Plasma and urine samples from 454 ALS and 294 control participants were analysed. Elevated levels of individual metals, including copper, selenium and zinc, significantly associated with ALS risk and survival. ERS representing metal mixtures strongly associated with ALS risk (plasma, OR=2.95, CI=2.38-3.62, p<0.001; urine, OR=3.10, CI=2.43-3.97, p<0.001) and poorer ALS survival (plasma, HR=1.37, CI=1.20-1.58, p<0.001; urine, HR=1.44, CI=1.23-1.67, p<0.001). Addition of the ALS-PGS or metal-PGS did not alter the significance of metals with ALS risk and survival. Occupations with high potential of metal exposure associated with elevated ERS. Additionally, occupational and non-occupational metal exposures were associated with measured plasma and urine metals.

CONCLUSION: Metals in plasma and urine associated with increased ALS risk and reduced survival, independent of genetic risk, and correlated with occupational and non-occupational metal exposures. These data underscore the significance of metal exposure in ALS risk and progression.}, } @article {pmid39106320, year = {2024}, author = {Dong, D and Zhang, Z and Li, Y and Latallo, MJ and Wang, S and Nelson, B and Wu, R and Krishnan, G and Gao, FB and Wu, B and Sun, S}, title = {Poly-GR repeats associated with ALS/FTD gene C9ORF72 impair translation elongation and induce a ribotoxic stress response in neurons.}, journal = {Science signaling}, volume = {17}, number = {848}, pages = {eadl1030}, pmid = {39106320}, issn = {1937-9145}, support = {RF1 NS101986/NS/NINDS NIH HHS/United States ; R21 AG072078/AG/NIA NIH HHS/United States ; T32 GM008403/GM/NIGMS NIH HHS/United States ; R01 NS107347/NS/NINDS NIH HHS/United States ; RF1 NS113820/NS/NINDS NIH HHS/United States ; R37 NS057553/NS/NINDS NIH HHS/United States ; RF1 NS127925/NS/NINDS NIH HHS/United States ; }, mesh = {*C9orf72 Protein/genetics/metabolism ; *Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology ; Humans ; *Frontotemporal Dementia/genetics/metabolism/pathology ; *Neurons/metabolism/pathology ; *Induced Pluripotent Stem Cells/metabolism ; *DNA Repeat Expansion/genetics ; Peptide Chain Elongation, Translational ; p38 Mitogen-Activated Protein Kinases/metabolism/genetics ; Stress, Physiological/genetics ; Ribosomes/metabolism/genetics ; }, abstract = {Hexanucleotide repeat expansion in the C9ORF72 gene is the most frequent inherited cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The expansion results in multiple dipeptide repeat proteins, among which arginine-rich poly-GR proteins are highly toxic to neurons and decrease the rate of protein synthesis. We investigated whether the effect on protein synthesis contributes to neuronal dysfunction and degeneration. We found that the expression of poly-GR proteins inhibited global translation by perturbing translation elongation. In iPSC-differentiated neurons, the translation of transcripts with relatively slow elongation rates was further slowed, and stalled, by poly-GR. Elongation stalling increased ribosome collisions and induced a ribotoxic stress response (RSR) mediated by ZAKα that increased the phosphorylation of the kinase p38 and promoted cell death. Knockdown of ZAKα or pharmacological inhibition of p38 ameliorated poly-GR-induced toxicity and improved the survival of iPSC-derived neurons from patients with C9ORF72-ALS/FTD. Our findings suggest that targeting the RSR may be neuroprotective in patients with ALS/FTD caused by repeat expansion in C9ORF72.}, } @article {pmid39106168, year = {2024}, author = {Glineburg, MR and Yildirim, E and Gomez, N and Rodriguez, G and Pak, J and Li, X and Altheim, C and Waksmacki, J and McInerney, GM and Barmada, SJ and Todd, PK}, title = {Stress granule formation helps to mitigate neurodegeneration.}, journal = {Nucleic acids research}, volume = {52}, number = {16}, pages = {9745-9759}, pmid = {39106168}, issn = {1362-4962}, support = {2018-03843//Swedish Research Council/ ; //Ann Arbor Active Against ALS/ ; T32 NS076401/NS/NINDS NIH HHS/United States ; BLRD BX004842//Veterans Affairs/ ; I01 BX004842/BX/BLRD VA/United States ; P50HD104463/NH/NIH HHS/United States ; R01 NS099280/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; *Stress Granules/metabolism ; *Neurodegenerative Diseases/metabolism/genetics ; *Amyotrophic Lateral Sclerosis/metabolism/genetics ; Humans ; *Neurons/metabolism ; *Frontotemporal Dementia/metabolism/genetics ; RNA Recognition Motif Proteins/metabolism/genetics ; Drosophila Proteins/metabolism/genetics ; Poly-ADP-Ribose Binding Proteins/metabolism/genetics ; Mice ; Drosophila melanogaster/metabolism/genetics ; RNA Helicases/metabolism/genetics ; Ataxia/genetics/metabolism ; DNA Helicases/metabolism/genetics ; Alphavirus/genetics/metabolism ; Rats ; Carrier Proteins/metabolism ; Drosophila/metabolism ; Cytoplasmic Granules/metabolism ; Stress, Physiological ; DNA-Binding Proteins ; }, abstract = {Cellular stress pathways that inhibit translation initiation lead to transient formation of cytoplasmic RNA/protein complexes known as stress granules. Many of the proteins found within stress granules and the dynamics of stress granule formation and dissolution are implicated in neurodegenerative disease. Whether stress granule formation is protective or harmful in neurodegenerative conditions is not known. To address this, we took advantage of the alphavirus protein nsP3, which selectively binds dimers of the central stress granule nucleator protein G3BP and markedly reduces stress granule formation without directly impacting the protein translational inhibitory pathways that trigger stress granule formation. In Drosophila and rodent neurons, reducing stress granule formation with nsP3 had modest impacts on lifespan even in the setting of serial stress pathway induction. In contrast, reducing stress granule formation in models of ataxia, amyotrophic lateral sclerosis and frontotemporal dementia largely exacerbated disease phenotypes. These data support a model whereby stress granules mitigate, rather than promote, neurodegenerative cascades.}, } @article {pmid39106020, year = {2024}, author = {Mirmotahari, SA and Aliomrani, M and Hassanzadeh, F and Sirous, H and Rostami, M}, title = {Hybrid derivatives containing dimethyl fumarate and benzothiazole scaffolds for the potential treatment of multiple sclerosis; in silico & in vivo study.}, journal = {Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences}, volume = {32}, number = {2}, pages = {599-615}, pmid = {39106020}, issn = {2008-2231}, mesh = {*Dimethyl Fumarate/pharmacology/chemistry ; *Multiple Sclerosis/drug therapy ; Animals ; *Molecular Docking Simulation ; *Benzothiazoles/chemistry/pharmacology ; *Riluzole/pharmacology/chemistry ; Mice ; *Mice, Inbred C57BL ; Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors/metabolism ; Male ; Cuprizone ; Disease Models, Animal ; Computer Simulation ; Neuroprotective Agents/pharmacology/chemistry ; Remyelination/drug effects ; }, abstract = {BACKGROUND: Multiple Sclerosis (MS) is a chronic autoimmune, inflammatory neurological disease of the CNS. Riluzole and dimethyl fumarate (DMF) are two FDA-approved drugs to treat amyotrophic lateral sclerosis (ALS) and MS. Riluzole (a benzothiazole derivative) inhibits glutamate release from nerve terminals by antagonizing the N-Methyl-D-Aspartate (NMDA) receptor, and DMF upregulates anti-oxidative pathways.

OBJECTIVES: Herein, using molecular hybridization strategy, we synthesized some new hybrid structures of Riluzole and DMF through some common successive synthetic pathways for evaluating their potential activity for remyelination in MS treatment.

METHODS: Molecular docking experiments assessed the binding affinity of proposed structures to the NMDA active site. The designed structures were synthesized and purified based on well-known chemical synthesis procedures. Afterward, in vivo evaluation for their activity was done in the C57Bl/6 Cuprizone-induced demyelination MS model.

RESULTS AND CONCLUSION: The proposed derivatives were recognized to be potent enough based on docking studies (ΔGbind of all derivatives were -7.2 to -7.52 compare to the Ifenprodil (-6.98) and Riluzole (-4.42)). The correct structures of desired derivatives were confirmed using spectroscopic methods. Based on in vivo studies, D4 and D6 derivatives exhibited the best pharmacological results, although only D6 showed a statistically significant difference compared to the control. Also, for D4 and D6 derivatives, myelin staining confirmed reduced degeneration in the corpus callosum. Consequently, D4 and D6 derivatives are promising candidates for developing new NMDA antagonists with therapeutic value against MS disorders.}, } @article {pmid39105912, year = {2024}, author = {Andrysiak, K and Stępniewski, J and Spaczyńska-Boczar, M and Łapicka-Bodzioch, K and Słowik, A and Dulak, J}, title = {Generation of Human-Induced Pluripotent Stem Cells from Peripheral Blood Mononuclear Cells of C9ORF72-Associated Amyotrophic Lateral Sclerosis Patients.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {2835}, number = {}, pages = {135-146}, pmid = {39105912}, issn = {1940-6029}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/pathology ; *C9orf72 Protein/genetics/metabolism ; Cell Culture Techniques/methods ; *Cell Differentiation ; Cellular Reprogramming ; DNA Repeat Expansion ; *Induced Pluripotent Stem Cells/metabolism/cytology ; *Leukocytes, Mononuclear/metabolism ; }, abstract = {Disease modeling of neuromuscular disorders, such as amyotrophic lateral sclerosis (ALS), is hindered by limited accessibility of affected cells. This problem can be overcome by generation of human induced pluripotent stem cells (hiPSC), which can be then differentiated into required cells. Here, we describe the detailed protocol of hiPSC establishment from peripheral blood mononuclear cells (PBMC) of two ALS patients with detected expansion of G4C2 (GGGGCC) repeats in the first intron of C9ORF72 gene, known to be linked with the most common form of familial ALS.Successful PBMC reprogramming with non-integrating Sendai vectors was confirmed by expression of pluripotency markers: OCT4, NANOG, SSEA4, and TRA-1-60 in obtained hiPSC and their ability to differentiate into cells of three germ layers.The generated ALS-patient-specific hiPSC create a possibility for deciphering molecular basis of this devastating neuromuscular disease.}, } @article {pmid39104673, year = {2024}, author = {Rezvani, S and Hosseini-Zahraei, SH and Tootchi, A and Guger, C and Chaibakhsh, Y and Saberi, A and Chaibakhsh, A}, title = {A review on the performance of brain-computer interface systems used for patients with locked-in and completely locked-in syndrome.}, journal = {Cognitive neurodynamics}, volume = {18}, number = {4}, pages = {1419-1443}, pmid = {39104673}, issn = {1871-4080}, abstract = {Patients with locked-in syndrome (LIS) and complete locked-in syndrome (CLIS) own a fully functional brain restricted within a non-functional body. In order to help LIS patients stay connected with their surroundings, brain-computer interfaces (BCIs) and related technologies have emerged. BCIs translate brain activity into actions that can be performed by external devices enabling LIS patients to communicate, leading to an increase in their quality of life. The past decade has seen the rapid development of BCIs that have the potential to be used for patients with locked-in syndrome, from which a great deal is tested only on healthy subjects and not on actual patients. This study aims to (1) provide the readers with a comprehensive study that contributes to this growing area of research by exploring the performance of BCIs tested specifically on LIS and CLIS patients, (2) give an overview of different modalities and paradigms used in different stages of the locked-in syndrome, and (3) discuss the contributions and limitations of BCIs introduced for the LIS and CLIS patients in the state-of-the-art and lay a groundwork for researchers interested in this field.}, } @article {pmid39104562, year = {2024}, author = {Haikal, A and Ali, AR}, title = {Chemical composition and toxicity studies on Lantana camara L. flower essential oil and its in silico binding and pharmacokinetics to superoxide dismutase 1 for amyotrophic lateral sclerosis (ALS) therapy.}, journal = {RSC advances}, volume = {14}, number = {33}, pages = {24250-24264}, pmid = {39104562}, issn = {2046-2069}, abstract = {Using the gas chromatography mass spectrometry method, the chemical components of essential oil from flowers of Lantana camara growing in Egypt are analyzed. Through this investigation, 22 chemicals from floral oil were identified. Most of the oil is made up of sesquiterpene caryophyllene (15.51%) and monoterpene sabinene (14.90%). When the oil's composition was compared to oils extracted from the same plant on several continents, we observed that the essential components were largely the same with some difference in proportions and some compounds due to geographical differences. A molecular docking study of essential oil components was conducted with human superoxide dismutase 1, a target involved in the pathophysiology of amyotrophic lateral sclerosis (ALS). Isospathulenol showed a comparable docking score to the reference ligand bound to the dismutase enzyme. Isospathulenol showed a reasonable drug score with some safety concerns. In addition, isospathulenol is predicted to have high GI absorption, good permeability through the blood-brain barrier and reasonable bioavailability score with ease access to synthetic modifications. In addition, the same compound is devoid from any violation to Lipinski rules or any PAINS alerts. This may establish the promising characteristics of such a compound to be optimized into potential drug candidates for treatment of ALS.}, } @article {pmid39104446, year = {2024}, author = {Higgins, S and Dlamini, S and Hattingh, M and Rambharose, S and Theron, E and Stassen, W}, title = {Views and perceptions of advanced life support practitioners on initiating, withholding and terminating resuscitation in out-of-hospital cardiac arrest in the Emergency Medical Services of South Africa.}, journal = {Resuscitation plus}, volume = {19}, number = {}, pages = {100709}, pmid = {39104446}, issn = {2666-5204}, abstract = {INTRODUCTION: This study aimed to explore the views and perceptions of Advanced Life Support (ALS) practitioners in two South African provinces on initiating, withholding, and terminating resuscitation in OHCA.

METHODOLOGY: Semi-structured one-on-one interviews were conducted with operational ALS practitioners working within the prehospital setting in the Western Cape and Free State provinces. Recorded interviews were transcribed and subjected to inductive-dominant, manifest content analysis. After familiarisation with the data, meaning units were condensed, codes were applied and collated into categories that were then assessed, reviewed, and refined repeatedly.

RESULTS: A total of 18 ALS providers were interviewed. Five main categories were developed from the data analysis: 1) assessment of prognosis, 2) internal factors affecting decision-making, 3) external factors affecting decision-making, 4) system challenges, and 5) ideas for improvement. Factors influencing the assessment of prognosis were history, clinical presentation, and response to resuscitation. Internal factors affecting decision-making were driven by emotion and contemplation. External factors affecting decision-making included family, safety, and disposition. System challenges relating to bystander response and resources were identified. Ideas for improvement in training and support were brought forward.

CONCLUSION: Many factors influence OHCA decision-making in the Western Cape and Free State provinces, and numerous system challenges have been identified. The findings of this study can be used as a frame of reference for prehospital emergency care personnel and contribute to the development of context-specific guidelines.}, } @article {pmid39103661, year = {2024}, author = {Tomasicchio, G and Martines, G and Tartaglia, N and Buonfantino, M and Restini, E and Carlucci, B and Giove, C and Dezi, A and Ranieri, C and Logrieco, G and Vincenti, L and Ambrosi, A and Altomare, DF and De Fazio, M and Picciariello, A}, title = {Suture reinforcement using a modified cyanoacrylate glue to prevent anastomotic leak in colorectal surgery: a prospective multicentre randomized trial : The Rectal Anastomotic seaL (ReAL) trial.}, journal = {Techniques in coloproctology}, volume = {28}, number = {1}, pages = {95}, pmid = {39103661}, issn = {1128-045X}, mesh = {Humans ; *Anastomotic Leak/prevention & control/etiology ; Female ; Male ; Prospective Studies ; Aged ; Middle Aged ; *Cyanoacrylates/administration & dosage ; *Anastomosis, Surgical/adverse effects/methods ; *Rectum/surgery ; Tissue Adhesives/therapeutic use ; Suture Techniques ; Rectal Neoplasms/surgery ; Treatment Outcome ; }, abstract = {BACKGROUND: Anastomotic leakage (AL) is the most frequent life-threating complication following colorectal surgery. Several attempts have been made to prevent AL. This prospective, randomized, multicentre trial aimed to evaluate the safety and efficacy of nebulised modified cyanoacrylate in preventing AL after rectal surgery.

METHODS: Patients submitted to colorectal surgery for carcinoma of the high-medium rectum across five high-volume centres between June 2021 and January 2023 entered the study and were randomized into group A (anastomotic reinforcement with cyanoacrylate) and group B (no reinforcement) and followed up for 30 days. Anastomotic reinforcement was performed via nebulisation of 1 mL of a modified cyanoacrylate glue. Preoperative features and intraoperative and postoperative results were recorded and compared. The study was registered at ClinicalTrials.gov (ID number NCT03941938).

RESULTS: Out of 152 patients, 133 (control group, n = 72; cyanoacrylate group, n = 61) completed the follow-up. ALs were detected in nine patients (12.5%) in the control group (four grade B and five grade C) and in four patients (6.6%), in the cyanoacrylate group (three grade B and one grade C); however, despite this trend, the differences were not statistically significant (p = 0.36). However, Clavien-Dindo complications grade > 2 were significantly higher in the control group (12.5% vs. 3.3%, p = 0.04). No adverse effects related to the glue application were reported.

CONCLUSION: The role of modified cyanoacrylate application in AL prevention remains unclear. However its use to seal colorectal anastomoses is safe and could help to reduce severe postoperative complications.}, } @article {pmid39103493, year = {2024}, author = {Talaia, G and Bentley-DeSousa, A and Ferguson, SM}, title = {Lysosomal TBK1 responds to amino acid availability to relieve Rab7-dependent mTORC1 inhibition.}, journal = {The EMBO journal}, volume = {43}, number = {18}, pages = {3948-3967}, pmid = {39103493}, issn = {1460-2075}, support = {R01 GM105718/GM/NIGMS NIH HHS/United States ; ASAP-000580//Michael J. Fox Foundation for Parkinson's Research (MJFF)/ ; ASAP-000580//Aligning Science Across Parkinson's (ASAP)/ ; GM105718//HHS | NIH | National Institute of General Medical Sciences (NIGMS)/ ; }, mesh = {Humans ; *Amino Acids/metabolism ; Amyotrophic Lateral Sclerosis/metabolism/genetics/pathology ; Frontotemporal Dementia/metabolism/genetics/pathology ; HEK293 Cells ; *Lysosomes/metabolism ; *Mechanistic Target of Rapamycin Complex 1/metabolism/genetics ; Phosphorylation ; *Protein Serine-Threonine Kinases/metabolism/genetics ; rab GTP-Binding Proteins/metabolism/genetics ; *rab7 GTP-Binding Proteins ; Signal Transduction ; }, abstract = {Lysosomes play a pivotal role in coordinating macromolecule degradation and regulating cell growth and metabolism. Despite substantial progress in identifying lysosomal signaling proteins, understanding the pathways that synchronize lysosome functions with changing cellular demands remains incomplete. This study uncovers a role for TANK-binding kinase 1 (TBK1), well known for its role in innate immunity and organelle quality control, in modulating lysosomal responsiveness to nutrients. Specifically, we identify a pool of TBK1 that is recruited to lysosomes in response to elevated amino acid levels. This lysosomal TBK1 phosphorylates Rab7 on serine 72. This is critical for alleviating Rab7-mediated inhibition of amino acid-dependent mTORC1 activation. Furthermore, a TBK1 mutant (E696K) associated with amyotrophic lateral sclerosis and frontotemporal dementia constitutively accumulates at lysosomes, resulting in elevated Rab7 phosphorylation and increased mTORC1 activation. This data establishes the lysosome as a site of amino acid regulated TBK1 signaling that is crucial for efficient mTORC1 activation. This lysosomal pool of TBK1 has broader implications for lysosome homeostasis, and its dysregulation could contribute to the pathogenesis of ALS-FTD.}, } @article {pmid39102937, year = {2024}, author = {Ali, F and Tang, Z and Mo, G and Zhang, B and Ling, X and Qiu, Z}, title = {Taxonomic and functional changes in wheat rhizosphere microbiome caused by imidazoline-based herbicide and genetic modification.}, journal = {Environmental research}, volume = {262}, number = {Pt 2}, pages = {119726}, doi = {10.1016/j.envres.2024.119726}, pmid = {39102937}, issn = {1096-0953}, mesh = {*Triticum/microbiology/genetics ; *Rhizosphere ; *Herbicides/toxicity ; *Microbiota/drug effects ; Soil Microbiology ; Plants, Genetically Modified/microbiology ; Imidazolines ; Imidazoles/toxicity ; Acetolactate Synthase/genetics ; Soil Pollutants/toxicity ; Bacteria/drug effects/genetics/classification ; }, abstract = {Genetically modified (GM) crop cultivation has received a lot of attention in recent years due to the substantial public debate. Consequently, an in-depth investigation of excessively used GM herbicide-tolerant crops is a vital step for the biosafety of genetically modified plants. Several studies have been conducted to study the impact of transgenic GM crops on soil microbial composition; however, research into the effects of non-transgenic GM crops is inadequate. In the current work, high-throughput sequencing was used to evaluate the impact of the acetolactate synthase (ALS)-mutant (WK170B), its control (YN19B), and the imazamox (IM) herbicide on the wheat rhizobiome. Under normal growth conditions, our work revealed a minimal impact of ALS-mutant WK170B on the rhizosphere microbiome compared to the control YN10B, except for some cyanobacterial microorganisms that showed a significant increase in abundance. This suggests that the gene mutation could potentially have a beneficial impact on the bacterial communities present in the rhizosphere. Following IM exposure, taxonomic analysis revealed a significant reduction in the relative abundance of Ralstonia pickettii and an unidentified member of the genus Ancylothrix 8 PC. Analyses of both alpha and beta diversity revealed a statistically significant increase in both microbial richness and species diversity. IM-induced relative abundance modulation was also evident through Linear discriminant analysis Effect Size (LEfSe), MetaStat, and heatmap analyses. The SIMPER analysis revealed that the microbial taxa Massilia, Limnobacter, Hydrogenophaga, Ralstonia, Nitrospira, and Ramlibacter exhibited the highest vulnerability to IM exposure. The functional attributes analysis revealed that the relative abundance of genes associated with the extracellular matrix-receptor interaction, which is responsible for structural support and stress response, increased significantly following IM exposure. Collectively, our study identifies key microbial taxa in the wheat rhizobiome that are sensitive to IM herbicides and provides a foundation for assessing the environmental risks associated with IM herbicide use.}, } @article {pmid39101689, year = {2024}, author = {Simão, S and Oliveira Santos, M and Gromicho, M and Pavão Martins, I and De Carvalho, M}, title = {Cognitive reserve as a modulator of cognitive decline and of behavioral symptoms in patients with amyotrophic lateral sclerosis.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {25}, number = {7-8}, pages = {726-736}, doi = {10.1080/21678421.2024.2385684}, pmid = {39101689}, issn = {2167-9223}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/psychology/complications/physiopathology ; Male ; Female ; *Cognitive Reserve/physiology ; Middle Aged ; *Cognitive Dysfunction/etiology/genetics/physiopathology/psychology ; Aged ; Neuropsychological Tests ; Behavioral Symptoms/etiology ; C9orf72 Protein/genetics ; Prospective Studies ; Adult ; Executive Function/physiology ; }, abstract = {Introduction: Amyotrophic lateral sclerosis (ALS) has heterogeneous manifestations ranging from motor neuron degeneration to cognitive and behavioral impairment. This study aims to clarify the interactions between cognition and behavioral symptoms with relevant disease predictors and with cognitive reserve (CR), quantified through education, physical activity, and occupation proxies. Methods: A prospective sample of 162 ALS patients and 61 controls were evaluated with the Edinburgh Cognitive and Behavioral ALS Screen (ECAS) (dependent variable), a Cognitive Reserve Index questionnaire (CRIq) and demographic data (age and sex), and, for patients, clinical variables: disease duration, site of onset, the ALS Functional Rating Scale (ALSFRS), forced vital capacity (FVC), and gene mutation chromosome 9 open reading frame 72 (C9orf72) (independent variables). Multiple regression and mediation analyses were performed to predict cognitive and behavioral symptoms. Results: For the ALS group, the statistical model explained 38.8% of variance in ECAS total (p < 0.001), 59.4% of executive functions (p < 0.001), and 55% of behavioral symptoms (p < 0.001). For controls, it accounted for 52.8% of variance in ECAS total (p < 0.001). Interaction effects and mediation analysis showed CR is an ECAS total modulator, with a differential effect within groups (p < 0.001). Verbal fluency was the single best cognitive score to differentiate patients from controls (p = 0.004), and the gene mutation C9orf72 was found to be a behavioral symptom' predictor in patients (p = 0.009). Conclusion: This study supports the proposed concept that CR acts as a cognitive modulator in ALS patients and healthy individuals. Moreover, CR also modulates behavioral manifestations in ALS.}, } @article {pmid39101354, year = {2024}, author = {Faleco, FA and Machado, FM and Bobadilla, LK and Tranel, PJ and Stoltenberg, D and Werle, R}, title = {Resistance to protoporphyrinogen oxidase inhibitors in giant ragweed (Ambrosia trifida).}, journal = {Pest management science}, volume = {80}, number = {12}, pages = {6211-6221}, doi = {10.1002/ps.8349}, pmid = {39101354}, issn = {1526-4998}, mesh = {*Protoporphyrinogen Oxidase/genetics/antagonists & inhibitors ; *Herbicide Resistance/genetics ; *Herbicides/pharmacology ; *Ambrosia ; Plant Weeds/drug effects/genetics/enzymology ; Plant Proteins/genetics/metabolism ; Acetolactate Synthase/genetics/antagonists & inhibitors ; Enzyme Inhibitors/pharmacology ; Weed Control ; }, abstract = {BACKGROUND: Giant ragweed (Ambrosia trifida L.) is one of the most troublesome weed species in corn (Zea mays L.) and soybean [Glycine max (L.) Merr.] cropping systems. Following numerous reports in 2018 of suspected herbicide resistance in several Ambrosia trifida populations from Wisconsin, our objective was to characterize the response of these accessions to acetolactate synthase (ALS), enolpyruvyl shikimate phosphate synthase (EPSPS), and protoporphyrinogen oxidase (PPO) inhibitors applied POST.

RESULTS: Four accessions (AT1, AT4, AT6, and AT10) exhibited ≥ 50% plant survival after exposure to the cloransulam 3× rate. Two accessions (AT8 and AT10) and one accession (AT2) exhibited ≥ 50% plant survival after exposure to glyphosate and fomesafen 1× rates, respectively. The AT10 accession exhibited multiple resistance to cloransulam and glyphosate. The AT12 accession was 28.8-fold resistant to fomesafen and 3.7-fold resistant to lactofen. A codon change in PPX2 conferring a R98L substitution was identified as the most likely mechanism conferring PPO-inhibitor resistance.

CONCLUSION: To our knowledge, this is the first confirmed case of PPO-inhibitor resistance in Ambrosia trifida globally and we identified the genetic mutation likely conferring resistance. Proactive and diversified integrated weed management strategies are of paramount importance for sustainable long-term Ambrosia trifida management. © 2024 The Author(s). Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.}, } @article {pmid39100390, year = {2024}, author = {Johnson, G and Tabner, A and Tilbury, N and Wesson, A and Hughes, GD and Elder, R and Bryson, P}, title = {Development of an algorithm to guide management of cardiorespiratory arrest in a diving bell.}, journal = {Resuscitation plus}, volume = {19}, number = {}, pages = {100724}, pmid = {39100390}, issn = {2666-5204}, abstract = {AIM: The management of cardiorespiratory arrest in a diving bell presents multiple clinical, technical, and environmental considerations that standard resuscitation algorithms do not address, and no situation-specific algorithm exists. The development and testing of an algorithm to guide the management of cardiorespiratory arrest in a bell is described.

METHODS: An iterative approach to algorithm development was used. Phase 1 involved a small multidisciplinary group and took place in a simulation centre and a decommissioned diving bell. The algorithm was then refined in a purpose-build simulation complex with repeated simulation by a group of divers, and with input from industry experts. ALS principles were followed unless contextual or technical factors necessitated deviation.

RESULTS: Clinical and technical aspects of the resuscitation are addressed. Key priorities that conflict with standard ALS principles are: prioritisation of rescue breaths; use of mechanical CPR when available; and the provision of CPR with the casualty in a seated position where necessary.

CONCLUSION: This is the first algorithm to guide the delivery of resuscitation in a diving bell. It incorporates adapted ALS principles and available data concerning compression technique effectiveness, and was informed by industry and clinical expertise. It provides guiding principles that can be adapted to setting-specific needs, and we would encourage its industry-wide international adoption.}, } @article {pmid39099373, year = {2024}, author = {Serangeli, I and Diamanti, T and De Jaco, A and Miranda, E}, title = {Role of mitochondria-endoplasmic reticulum contacts in neurodegenerative, neurodevelopmental and neuropsychiatric conditions.}, journal = {The European journal of neuroscience}, volume = {60}, number = {5}, pages = {5040-5068}, doi = {10.1111/ejn.16485}, pmid = {39099373}, issn = {1460-9568}, support = {//Sapienza Università di Roma/ ; //Sapienza University of Rome/ ; }, mesh = {Humans ; *Mitochondria/metabolism ; *Neurodegenerative Diseases/metabolism/pathology ; *Endoplasmic Reticulum/metabolism ; Animals ; *Neurodevelopmental Disorders/metabolism ; *Mental Disorders/metabolism/physiopathology ; Mitochondria Associated Membranes ; }, abstract = {Mitochondria-endoplasmic reticulum contacts (MERCs) mediate a close and continuous communication between both organelles that is essential for the transfer of calcium and lipids to mitochondria, necessary for cellular signalling and metabolic pathways. Their structural and molecular characterisation has shown the involvement of many proteins that bridge the membranes of the two organelles and maintain the structural stability and function of these contacts. The crosstalk between the two organelles is fundamental for proper neuronal function and is now recognised as a component of many neurological disorders. In fact, an increasing proportion of MERC proteins take part in the molecular and cellular basis of pathologies affecting the nervous system. Here we review the alterations in MERCs that have been reported for these pathologies, from neurodevelopmental and neuropsychiatric disorders to neurodegenerative diseases. Although mitochondrial abnormalities in these debilitating conditions have been extensively attributed to the high energy demand of neurons, a distinct role for MERCs is emerging as a new field of research. Understanding the molecular details of such alterations may open the way to new paths of therapeutic intervention.}, } @article {pmid39099169, year = {2024}, author = {Wang, J and Qiu, Y and Yang, L and Wang, J and He, J and Tang, C and Yang, Z and Hong, W and Yang, B and He, Q and Weng, Q}, title = {Preserving mitochondrial homeostasis protects against drug-induced liver injury via inducing OPTN (optineurin)-dependent Mitophagy.}, journal = {Autophagy}, volume = {20}, number = {12}, pages = {2677-2696}, pmid = {39099169}, issn = {1554-8635}, mesh = {*Mitophagy/drug effects/physiology ; *Homeostasis/drug effects ; *Membrane Transport Proteins/metabolism ; Animals ; *Cell Cycle Proteins/metabolism ; Humans ; *Valosin Containing Protein/metabolism ; *Chemical and Drug Induced Liver Injury/metabolism ; *Hepatocytes/metabolism/drug effects ; Mitochondria/metabolism/drug effects ; Mice ; Transcription Factor TFIIIA/metabolism/genetics ; Mice, Inbred C57BL ; Beclin-1/metabolism ; Mitochondria, Liver/metabolism/drug effects ; }, abstract = {Disruption of mitochondrial function is observed in multiple drug-induced liver injuries (DILIs), a significant global health threat. However, how the mitochondrial dysfunction occurs and whether maintain mitochondrial homeostasis is beneficial for DILIs remains unclear. Here, we show that defective mitophagy by OPTN (optineurin) ablation causes disrupted mitochondrial homeostasis and aggravates hepatocytes necrosis in DILIs, while OPTN overexpression protects against DILI depending on its mitophagic function. Notably, mass spectrometry analysis identifies a new mitochondrial substrate, GCDH (glutaryl-CoA dehydrogenase), which can be selectively recruited by OPTN for mitophagic degradation, and a new cofactor, VCP (valosin containing protein) that interacts with OPTN to stabilize BECN1 during phagophore assembly, thus boosting OPTN-mediated mitophagy initiation to clear damaged mitochondria and preserve mitochondrial homeostasis in DILIs. Then, the accumulation of OPTN in different DILIs is further validated with a protective effect, and pyridoxine is screened and established to alleviate DILIs by inducing OPTN-mediated mitophagy. Collectively, our findings uncover a dual role of OPTN in mitophagy initiation and implicate the preservation of mitochondrial homeostasis via inducing OPTN-mediated mitophagy as a potential therapeutic approach for DILIs.Abbreviation: AILI: acetaminophen-induced liver injury; ALS: amyotrophic lateral sclerosis; APAP: acetaminophen; CALCOCO2/NDP52: calcium binding and coiled-coil domain 2; CHX: cycloheximide; Co-IP: co-immunoprecipitation; DILI: drug-induced liver injury; FL: full length; GCDH: glutaryl-CoA dehydrogenase; GOT1/AST: glutamic-oxaloacetic transaminase 1; GO: gene ontology; GSEA: gene set enrichment analysis; GPT/ALT: glutamic - pyruvic transaminase; INH: isoniazid; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MMP: mitochondrial membrane potential; MST: microscale thermophoresis; MT-CO2/COX-II: mitochondrially encoded cytochrome c oxidase II; OPTN: optineurin; PINK1: PTEN induced kinase 1; PRKN: parkin RBR E3 ubiquitin protein ligase; TIMM23: translocase of inner mitochondrial membrane 23; TOMM20: translocase of outer mitochondrial membrane 20; TSN: toosendanin; VCP: valosin containing protein, WIPI2: WD repeat domain, phosphoinositide interacting 2.}, } @article {pmid39098767, year = {2025}, author = {Endo, F}, title = {Deciphering the spectrum of astrocyte diversity: Insights into molecular, morphological, and functional dimensions in health and neurodegenerative diseases.}, journal = {Neuroscience research}, volume = {210}, number = {}, pages = {1-10}, doi = {10.1016/j.neures.2024.07.008}, pmid = {39098767}, issn = {1872-8111}, mesh = {Humans ; *Astrocytes/pathology/physiology/metabolism ; *Neurodegenerative Diseases/pathology/metabolism/physiopathology ; Animals ; }, abstract = {Astrocytes are the most abundant and morphologically complex glial cells that play active roles in the central nervous system (CNS). Recent research has identified shared and region-specific astrocytic genes and functions, elucidated the cellular origins of their regional diversity, and uncovered the molecular networks for astrocyte morphology, which are essential for their functional complexity. Reactive astrocytes exhibit a wide range of functional diversity in a context-specific manner in CNS disorders. This review discusses recent advances in understanding the molecular and morphological diversity of astrocytes in healthy individuals and those with neurodegenerative diseases, such as Alzheimer's disease, Huntington's disease, and amyotrophic lateral sclerosis.}, } @article {pmid39098618, year = {2024}, author = {Koehn, LM and Jalaldeen, R and Pelle, J and Nicolazzo, JA}, title = {Plasma, brain and spinal cord concentrations of caffeine are reduced in the SOD1[G93A] mouse model of amyotrophic lateral sclerosis following oral administration.}, journal = {European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V}, volume = {203}, number = {}, pages = {114434}, doi = {10.1016/j.ejpb.2024.114434}, pmid = {39098618}, issn = {1873-3441}, mesh = {Animals ; *Caffeine/administration & dosage/pharmacokinetics ; *Amyotrophic Lateral Sclerosis/drug therapy/metabolism ; *Spinal Cord/metabolism/drug effects ; Male ; Female ; Mice ; Administration, Oral ; *Brain/metabolism/drug effects ; *Disease Models, Animal ; *Mice, Transgenic ; Superoxide Dismutase-1/genetics/metabolism ; Digoxin/pharmacokinetics/administration & dosage ; Sulfasalazine/pharmacokinetics/administration & dosage ; Intestinal Absorption/drug effects/physiology ; }, abstract = {Modifications to the small intestine and liver are known to occur during the symptomatic disease period of amyotrophic lateral sclerosis (ALS), a member of the motor neuron disease (MND) family of neurodegenerative disorders. How these modifications impact on oral absorption and pharmacokinetics of drugs remains unknown. In this study, model drugs representing different mechanisms of intestinal transport (caffeine for passive diffusion, digoxin for P-glycoprotein efflux, and sulfasalazine for breast cancer resistance protein efflux) were administered via oral gavage to postnatal day 114-120 male and female SOD1[G93A] mice (model of familial ALS) and wild-type (WT) littermates. Samples of blood, brain and spinal cord were taken at either 15, 30, 60 or 180 min after administration. In addition, the in vivo gastric emptying of 70 kDa fluorescein isothiocyanate-dextran (FITC-dextran) and the ex vivo intestinal permeability of caffeine were assessed. The area under the plasma concentration-time curves (AUCplasma) of digoxin and sulfasalazine were not significantly different between SOD1[G93A] and WT mice for both sexes. However, the AUCplasma of caffeine was significantly lower (female: 0.79-fold, male: 0.76-fold) in SOD1[G93A] compared to WT mice, which was associated with lower AUCbrain (female: 0.76-fold, male: 0.80-fold) and AUCspinal cord (female: 0.81-fold, male: 0.82-fold). The AUCstomach of caffeine was significantly higher (female: 1.5-fold, male: 1.9-fold) in SOD1[G93A] compared to WT mice, suggesting reduced gastric emptying in SOD1[G93A] mice. In addition, there was a significant reduction in gastric emptying of FITC-dextran (0.66-fold) and ex vivo intestinal permeability of caffeine (0.52-fold) in male SOD1[G93A] compared to WT mice. Reduced systemic and brain/spinal cord exposure of caffeine in SOD1[G93A] mice may therefore result from alterations to gastric emptying and small intestinal permeability. Specific dosing requirements may therefore be required for certain medicines in ALS to ensure that they remain in a safe and effective concentration range.}, } @article {pmid39098187, year = {2024}, author = {R K Roy, A and Noohi, F and Morris, NA and Ljubenkov, P and Heuer, H and Fong, J and Hall, M and Lario Lago, A and Rankin, KP and Miller, BL and Boxer, AL and Rosen, HJ and Seeley, WW and Perry, DC and Yokoyama, JS and Lee, SE and Sturm, VE}, title = {Basal parasympathetic deficits in C9orf72 hexanucleotide repeat expansion carriers relate to smaller frontoinsula and thalamus volume and lower empathy.}, journal = {NeuroImage. Clinical}, volume = {43}, number = {}, pages = {103649}, pmid = {39098187}, issn = {2213-1582}, support = {R01 AG052496/AG/NIA NIH HHS/United States ; R01 AG059794/AG/NIA NIH HHS/United States ; R01 AG062758/AG/NIA NIH HHS/United States ; }, mesh = {Humans ; Female ; Male ; Middle Aged ; *C9orf72 Protein/genetics ; Aged ; *Empathy/physiology ; *Frontotemporal Dementia/genetics/physiopathology/pathology/diagnostic imaging ; *DNA Repeat Expansion/genetics ; *Magnetic Resonance Imaging/methods ; *Parasympathetic Nervous System/physiopathology ; *Thalamus/diagnostic imaging/physiopathology/pathology ; *Cognitive Dysfunction/physiopathology/genetics/diagnostic imaging/etiology/pathology ; Heterozygote ; Respiratory Sinus Arrhythmia/physiology ; Cerebral Cortex/diagnostic imaging/physiopathology/pathology ; }, abstract = {Diminished basal parasympathetic nervous system activity is a feature of frontotemporal dementia that relates to left frontoinsula dysfunction and empathy impairment. Individuals with a pathogenic expansion of the hexanucleotide repeat in chromosome 9 open reading frame 72 (C9orf72), the most common genetic cause of frontotemporal dementia and amyotrophic lateral sclerosis, provide a unique opportunity to examine whether parasympathetic activity is disrupted in genetic forms of frontotemporal dementia and to investigate when parasympathetic deficits manifest in the pathophysiological cascade. We measured baseline respiratory sinus arrhythmia, a parasympathetic measure of heart rate variability, over two minutes in a sample of 102 participants that included 19 asymptomatic expansion carriers (C9[+] asymp), 14 expansion carriers with mild cognitive impairment (C9[+] MCI), 16 symptomatic expansion carriers with frontotemporal dementia (C9[+] FTD), and 53 expansion-negative healthy controls (C9[-] HC) who also underwent structural magnetic resonance imaging. In follow-up analyses, we compared baseline respiratory sinus arrhythmia in the C9[+] FTD group with an independent age-, sex-, and clinical severity-matched group of 26 people with sporadic behavioral variant frontotemporal dementia. The Frontotemporal Lobar Degeneration-modified Clinical Dementia Rating-Sum of Boxes score was used to quantify behavioral symptom severity, and informant ratings on the Interpersonal Reactivity Index provided measures of participants' current emotional (empathic concern) and cognitive (perspective-taking) empathy. Results indicated that the C9[+] FTD group had lower baseline respiratory sinus arrhythmia than the C9[+] MCI, C9[+] asymp, and C9[-] HC groups, a deficit that was comparable to that of sporadic behavioral variant frontotemporal dementia. Linear regression analyses indicated that lower baseline respiratory sinus arrhythmia was associated with worse behavioral symptom severity and lower empathic concern and perspective-taking across the C9orf72 expansion carrier clinical spectrum. Whole-brain voxel-based morphometry analyses in participants with C9orf72 pathogenic expansions found that lower baseline respiratory sinus arrhythmia correlated with smaller gray matter volume in the left frontoinsula and bilateral thalamus, key structures that support parasympathetic function, and in the bilateral parietal lobes, occipital lobes, and cerebellum, regions that are also vulnerable in individuals with C9orf72 expansions. This study provides novel evidence that basal parasympathetic functioning is diminished in FTD due to C9orf72 expansions and suggests that baseline respiratory sinus arrhythmia may be a potential non-invasive biomarker that is sensitive to behavioral symptoms in the early stages of disease.}, } @article {pmid39097850, year = {2024}, author = {Luan, T and Li, Q and Huang, Z and Feng, Y and Xu, D and Zhou, Y and Hu, Y and Wang, T}, title = {Axonopathy Underlying Amyotrophic Lateral Sclerosis: Unraveling Complex Pathways and Therapeutic Insights.}, journal = {Neuroscience bulletin}, volume = {40}, number = {11}, pages = {1789-1810}, pmid = {39097850}, issn = {1995-8218}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism/therapy ; Animals ; *Axons/pathology/metabolism ; Mitochondria/metabolism ; Motor Neurons/metabolism/pathology ; }, abstract = {Amyotrophic Lateral Sclerosis (ALS) is a complex neurodegenerative disorder characterized by progressive axonopathy, jointly leading to the dying back of the motor neuron, disrupting both nerve signaling and motor control. In this review, we highlight the roles of axonopathy in ALS progression, driven by the interplay of multiple factors including defective trafficking machinery, protein aggregation, and mitochondrial dysfunction. Dysfunctional intracellular transport, caused by disruptions in microtubules, molecular motors, and adaptors, has been identified as a key contributor to disease progression. Aberrant protein aggregation involving TDP-43, FUS, SOD1, and dipeptide repeat proteins further amplifies neuronal toxicity. Mitochondrial defects lead to ATP depletion, oxidative stress, and Ca[2+] imbalance, which are regarded as key factors underlying the loss of neuromuscular junctions and axonopathy. Mitigating these defects through interventions including neurotrophic treatments offers therapeutic potential. Collaborative research efforts aim to unravel ALS complexities, opening avenues for holistic interventions that target diverse pathological mechanisms.}, } @article {pmid39097602, year = {2024}, author = {Lehmann, J and Aly, A and Steffke, C and Fabbio, L and Mayer, V and Dikwella, N and Halablab, K and Roselli, F and Seiffert, S and Boeckers, TM and Brenner, D and Kabashi, E and Mulaw, M and Ho, R and Catanese, A}, title = {Heterozygous knockout of Synaptotagmin13 phenocopies ALS features and TP53 activation in human motor neurons.}, journal = {Cell death & disease}, volume = {15}, number = {8}, pages = {560}, pmid = {39097602}, issn = {2041-4889}, support = {SFB 1506-Project 01//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; 2019_A111//Else Kröner-Fresenius-Stiftung (Else Kroner-Fresenius Foundation)/ ; }, mesh = {Humans ; *Tumor Suppressor Protein p53/metabolism/genetics ; *Motor Neurons/metabolism/pathology ; *Synaptotagmins/metabolism/genetics ; *Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology ; Heterozygote ; Phenotype ; Induced Pluripotent Stem Cells/metabolism/pathology ; Cell Differentiation/genetics ; Gene Knockout Techniques ; }, abstract = {Spinal motor neurons (MNs) represent a highly vulnerable cellular population, which is affected in fatal neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA). In this study, we show that the heterozygous loss of SYT13 is sufficient to trigger a neurodegenerative phenotype resembling those observed in ALS and SMA. SYT13[+/-] hiPSC-derived MNs displayed a progressive manifestation of typical neurodegenerative hallmarks such as loss of synaptic contacts and accumulation of aberrant aggregates. Moreover, analysis of the SYT13[+/-] transcriptome revealed a significant impairment in biological mechanisms involved in motoneuron specification and spinal cord differentiation. This transcriptional portrait also strikingly correlated with ALS signatures, displaying a significant convergence toward the expression of pro-apoptotic and pro-inflammatory genes, which are controlled by the transcription factor TP53. Our data show for the first time that the heterozygous loss of a single member of the synaptotagmin family, SYT13, is sufficient to trigger a series of abnormal alterations leading to MN sufferance, thus revealing novel insights into the selective vulnerability of this cell population.}, } @article {pmid39097310, year = {2024}, author = {Christian, CS and Nkonki, L and Desmond, C and Hoegfeldt, C and Dube, S and Rochat, T and Stein, A}, title = {Protocol of a cost-effectiveness analysis of a combined intervention for depression and parenting compared with enhanced standard of care for perinatally depressed, HIV-positive women and their infants in rural South Africa.}, journal = {BMJ open}, volume = {14}, number = {8}, pages = {e082977}, pmid = {39097310}, issn = {2044-6055}, support = {/WT_/Wellcome Trust/United Kingdom ; MR/P006965/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Female ; Humans ; Infant ; Infant, Newborn ; Pregnancy ; *Cost-Effectiveness Analysis/methods ; Depression/therapy ; Depression, Postpartum/therapy/economics ; *HIV Infections ; Parenting ; Randomized Controlled Trials as Topic ; Rural Population ; South Africa ; Standard of Care ; Research Design ; }, abstract = {INTRODUCTION: Poverty, HIV and perinatal depression represent a triple threat to public health in sub-Saharan Africa because of their combined negative effects on parenting and child development. In the resource-constrained context of low-income and middle-income countries, a lay-counsellor-delivered intervention that combines a psychological and parenting intervention could offer the potential to mitigate the consequences of perinatal depression while also optimising scarce resources for healthcare.Measuring the cost-effectiveness of such a novel intervention will help decision-makers to better understand the relative costs and effects associated with replicating the intervention, thereby supporting evidence-based decision-making. This protocol sets out the methodological framework for analysing the cost-effectiveness of a cluster randomised controlled trial (RCT) that compares a combined intervention to enhanced standard of care when treating depressed, HIV-positive pregnant women and their infants in rural South Africa.

METHODS AND ANALYSIS: This cost-effectiveness analysis (CEA) protocol complies with the Consolidated Health Economic Evaluation Reporting Standards 2022 checklist. A societal perspective will be chosen.The proposed methods will determine the cost and efficiency of implementing the intervention as per the randomised control trial protocol, as well as the cost of replicating the intervention in a non-research setting. The costs will be calculated using an appropriately adjusted version of the Standardised Early Childhood Development Costing Tool.Primary health outcomes will be used in combination with costs to determine the cost per improvement in maternal perinatal depression at 12 months postnatal and the cost per improvement in child cognitive development at 24 months of age. To facilitate priority setting, the incremental cost-effectiveness ratios for improvements in child cognitive development will be ranked against six other child cognitive-development interventions according to Verguet et al's methodology (2022).A combination of activity-based and ingredient-based costing approaches will be used to identify, measure and value activities and inputs for all alternatives. Outcomes data will be sourced from the RCT team.

ETHICS AND DISSEMINATION: The University of Oxford is the sponsor of the CEA. Ethics approval has been obtained from the Human Sciences Research Council (HSRC, #REC 5/23/08/17), South Africa and the Oxford Tropical Research Ethics Committee (OxTREC #31-17), UK.Consent for publication is not applicable since no participant data are used in this protocol.We plan to disseminate the CEA results to key policymakers and researchers in the form of a policy brief, meetings and academic papers.

TRIAL REGISTRATION DETAILS: ISRCTN registry #11 284 870 (14/11/2017) and SANCTR DOH-27-102020-9097 (17/11/2017).}, } @article {pmid39096593, year = {2024}, author = {Ozeloglu, IG and Akman Aydin, E}, title = {Combining features on vertical ground reaction force signal analysis for multiclass diagnosing neurodegenerative diseases.}, journal = {International journal of medical informatics}, volume = {191}, number = {}, pages = {105542}, doi = {10.1016/j.ijmedinf.2024.105542}, pmid = {39096593}, issn = {1872-8243}, mesh = {Humans ; *Neurodegenerative Diseases/diagnosis ; Male ; Female ; Middle Aged ; Aged ; Amyotrophic Lateral Sclerosis/diagnosis ; Support Vector Machine ; Parkinson Disease/diagnosis ; Neural Networks, Computer ; Huntington Disease/diagnosis/physiopathology ; Signal Processing, Computer-Assisted ; Gait/physiology ; Algorithms ; }, abstract = {Neurodegenerative diseases (NDDs), which are caused by the degeneration of neurons and their functions, affect a significant part of the world's population. Although gait disorders are one of the critical and common markers to determine the presence of NDDs, diagnosing which NDD the patients have among a group of NDDs using gait data is still a significant challenge to be addressed. In this study, we addressed the multi-class classification of NDDs and aim to diagnose Parkinson's disease (PD), Amyotrophic lateral sclerosis disease (AD), and Huntington's disease (HD) from a group containing NDDs and healthy control subjects. We also examined the impact of disease-specific identified features derived from VGRF signals. Detrended Fluctuation Analysis (DFA), Dynamic Time Warping (DTW) and Autocorrelation (AC) were used for feature extraction on Vertical Ground Reaction Force (VGRF) signals. To compare the performance of the features, we employed Support Vector Machines, K-Nearest Neighbors, and Neural Networks as classifiers. In three-class problem addressing the classification of AD, PD and HD 93.3% accuracy rate was achieved, while in the four classes case, in which NDDs and HC groups were considered together, 93.5% accuracy rate was yielded. Considering the disease-specific impact of features, it is revealed that while DFA based features diagnose patients with AD with the highest accuracy, DTW has been shown to be more successful in diagnosing PD. AC based features provided the highest accuracy in diagnosing HD. Although gait disorder is common for NDDs, each disease may have its own distinctive gait rhythms; therefore, it is important to identify disease-specific patterns and parameters for the diagnosis of each disease. To increase the diagnostic accuracy, it is necessary to use a combination of features, which were effective for each disease diagnosis. Determining a limited number of disease-specific features would provide NDD diagnostic systems suitable to be deployed in edge-computing environments.}, } @article {pmid39096334, year = {2025}, author = {Paterson, M and Doeltgen, S and Francis, R}, title = {Sensory Changes Related to Swallowing in Motor Neurone Disease.}, journal = {Dysphagia}, volume = {40}, number = {2}, pages = {407-418}, pmid = {39096334}, issn = {1432-0460}, mesh = {Humans ; *Deglutition Disorders/physiopathology/etiology ; *Motor Neuron Disease/complications/physiopathology ; *Deglutition/physiology ; *Sensation Disorders/etiology/physiopathology ; *Sensation/physiology ; }, abstract = {Dysphagia is common in motor neurone disease (MND) and associated with negative health and psychosocial outcomes. Although largely considered a motor disease, a growing body of evidence suggests that MND can also affect the sensory system. As intact sensation is vital for safe swallowing, and sensory changes can influence the clinical management of dysphagia in people living with MND, this review evaluated and summarised the current evidence for sensory changes related to swallowing in MND. Of 3,481 articles originally identified, 29 met the inclusion criteria. Of these, 20 studies reported sensory changes, which included laryngeal sensation, taste, gag reflex, cough reflex, tongue sensation, smell, palatal and pharyngeal sensation, silent aspiration, and undefined sensation of the swallowing mechanism. Sensory changes were either described as decreased (n = 16) or heightened (n = 4). In the remaining nine studies, sensory function was reported as unaffected. The presence of changes to sensory function related to swallowing in MND remains inconclusive, although an increasing number of studies report sensory changes in some sensory domains. Future research is needed to evaluate the prevalence of sensory changes in MND and how such changes may influence dysphagia and its management.}, } @article {pmid39096043, year = {2024}, author = {Rabadi, MH and Russell, KA and Xu, C}, title = {Veterans with familial ALS and bulbar and respiratory presentations at onset had shorter survival.}, journal = {Science progress}, volume = {107}, number = {3}, pages = {368504241262902}, pmid = {39096043}, issn = {2047-7163}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/mortality/physiopathology/genetics/diagnosis ; Middle Aged ; Male ; *Veterans/statistics & numerical data ; Female ; Aged ; Age of Onset ; Prognosis ; Kaplan-Meier Estimate ; }, abstract = {OBJECTIVE: We sought to characterize the clinical prognostic factors in veterans with amyotrophic lateral sclerosis (ALS) followed in our ALS clinic.

BACKGROUND: ALS is a rare, progressive neurodegenerative condition associated with decreased survival compared to that in the normal population.

METHOD: The electronic medical records of 105 veterans diagnosed with ALS who are followed in our ALS clinic between 2010 and 2021 were reviewed. Approval from the institutional review board was obtained from the study protocol. Demographic and clinical variables included age at symptom onset, age at initial evaluation, survival (from symptom onset to death), gender, site of onset (appendicular, bulbar, and respiratory), initial amyotrophic lateral sclerosis functional-related score-revised (ALSFRS-R), total functional independence measure (TFIM) scores, initial forced vital capacity (FVC), and interventions (Riluzole, gastrostomy, noninvasive ventilation [NIV], and tracheostomy). Normally distributed data was expressed as mean ± standard deviation. Fischer's exact analysis of the distribution differences of categorical data. The Kaplan-Meier plot analyzed the time-to-event.

RESULTS: The mean (SD) age at symptom onset was 62.0 (11.1) years, age at diagnosis was 65 (11) years, with 72% of the patients being over 60 years at diagnosis. The median survival time from symptom onset was 4.12 (3) years. Limb-onset ALS (appendicular) was the most frequent (52%) followed by bulbar-onset ALS (43%). The mean ALSFRS-R and TFIM scores were 31 (8) and 91 (25), respectively. Family history (familial), bulbar, and respiratory presentation at diagnosis were associated with shorter survival times.

CONCLUSION: This study suggests that of the clinical prognostic factors veterans with familial ALS, bulbar, and respiratory onset at presentations had shorter survival. The presence of Agent Orange, PEG placement, and NIV did not affect survival.}, } @article {pmid39095145, year = {2024}, author = {Sheers, NL and Andersen, T and Chatwin, M}, title = {Airway Clearance in Neuromuscular Disease.}, journal = {Sleep medicine clinics}, volume = {19}, number = {3}, pages = {485-496}, doi = {10.1016/j.jsmc.2024.04.009}, pmid = {39095145}, issn = {1556-4088}, mesh = {Humans ; *Neuromuscular Diseases/therapy/physiopathology ; Respiratory Therapy/methods ; Cough/therapy/physiopathology ; Airway Management/methods ; }, abstract = {High-quality respiratory care and airway clearance is essential for people with neuromuscular disease (pwNMD) as respiratory tract infections are a major cause of morbidity and mortality. This review expands on published guidelines by highlighting the role of cough peak flow along with other options for cough evaluation, and discusses recent key research findings which have influenced the practice of respiratory therapy for pwNMD.}, } @article {pmid39094561, year = {2024}, author = {Gomes, C and Huang, KC and Harkin, J and Baker, A and Hughes, JM and Pan, Y and Tutrow, K and VanderWall, KB and Lavekar, SS and Hernandez, M and Cummins, TR and Canfield, SG and Meyer, JS}, title = {Induction of astrocyte reactivity promotes neurodegeneration in human pluripotent stem cell models.}, journal = {Stem cell reports}, volume = {19}, number = {8}, pages = {1122-1136}, pmid = {39094561}, issn = {2213-6711}, support = {R01 EY033022/EY/NEI NIH HHS/United States ; T32 GM148382/GM/NIGMS NIH HHS/United States ; U24 EY033269/EY/NEI NIH HHS/United States ; R01 NS053422/NS/NINDS NIH HHS/United States ; UL1 TR002529/TR/NCATS NIH HHS/United States ; }, mesh = {*Astrocytes/metabolism ; Humans ; *Pluripotent Stem Cells/metabolism/cytology ; *Coculture Techniques ; Neurodegenerative Diseases/metabolism/pathology ; Complement C3/metabolism ; Cell Differentiation ; Neurons/metabolism ; Alzheimer Disease/pathology/metabolism ; Phagocytosis ; Blood-Brain Barrier/metabolism ; Glaucoma/pathology/metabolism ; Amyotrophic Lateral Sclerosis/metabolism/pathology ; Calcium/metabolism ; Phenotype ; }, abstract = {Reactive astrocytes are known to exert detrimental effects upon neurons in several neurodegenerative diseases, yet our understanding of how astrocytes promote neurotoxicity remains incomplete, especially in human systems. In this study, we leveraged human pluripotent stem cell (hPSC) models to examine how reactivity alters astrocyte function and mediates neurodegeneration. hPSC-derived astrocytes were induced to a reactive phenotype, at which point they exhibited a hypertrophic profile and increased complement C3 expression. Functionally, reactive astrocytes displayed decreased intracellular calcium, elevated phagocytic capacity, and decreased contribution to the blood-brain barrier. Subsequently, co-culture of reactive astrocytes with a variety of neuronal cell types promoted morphological and functional alterations. Furthermore, when reactivity was induced in astrocytes from patient-specific hPSCs (glaucoma, Alzheimer's disease, and amyotrophic lateral sclerosis), the reactive state exacerbated astrocytic disease-associated phenotypes. These results demonstrate how reactive astrocytes modulate neurodegeneration, significantly contributing to our understanding of a role for reactive astrocytes in neurodegenerative diseases.}, } @article {pmid39092466, year = {2024}, author = {Soubannier, V and Chaineau, M and Gursu, L and Lépine, S and Kalaydjian, D and Sirois, J and Haghi, G and Rouleau, G and Durcan, TM and Stifani, S}, title = {Early nuclear phenotypes and reactive transformation in human iPSC-derived astrocytes from ALS patients with SOD1 mutations.}, journal = {Glia}, volume = {72}, number = {11}, pages = {2079-2094}, doi = {10.1002/glia.24598}, pmid = {39092466}, issn = {1098-1136}, support = {//ALS Canada/Brain Canada Hudson Translational Team Grant/ ; //Canada First Research Excellence Fund/ ; //ALS Canada/Brain Canada Discovery Grant/ ; }, mesh = {Humans ; *Astrocytes/metabolism/pathology ; *Amyotrophic Lateral Sclerosis/genetics/pathology/metabolism ; *Induced Pluripotent Stem Cells/metabolism ; *Superoxide Dismutase-1/genetics/metabolism ; *Mutation ; *Phenotype ; Cells, Cultured ; Cell Nucleus/metabolism ; Motor Neurons/pathology/metabolism ; Oxidative Stress/physiology/genetics ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the progressive death of motor neurons (MNs). Glial cells play roles in MN degeneration in ALS. More specifically, astrocytes with mutations in the ALS-associated gene Cu/Zn superoxide dismutase 1 (SOD1) promote MN death. The mechanisms by which SOD1-mutated astrocytes reduce MN survival are incompletely understood. To characterize the impact of SOD1 mutations on astrocyte physiology, we generated astrocytes from human induced pluripotent stem cell (iPSC) derived from ALS patients carrying SOD1 mutations, together with control isogenic iPSCs. We report that astrocytes harboring SOD1(A4V) and SOD1(D90A) mutations exhibit molecular and morphological changes indicative of reactive astrogliosis when compared to isogenic astrocytes. We show further that a number of nuclear phenotypes precede, or coincide with, reactive transformation. These include increased nuclear oxidative stress and DNA damage, and accumulation of the SOD1 protein in the nucleus. These findings reveal early cell-autonomous phenotypes in SOD1-mutated astrocytes that may contribute to the acquisition of a reactive phenotype involved in alterations of astrocyte-MN communication in ALS.}, } @article {pmid39473802, year = {2024}, author = {Lukac, M and Luben, H and Martin, AE and Simmons, Z and Geronimo, A}, title = {Spatial-Temporal Analysis of Gait in Amyotrophic Lateral Sclerosis Using Foot-Worn Inertial Sensors: An Observational Study.}, journal = {Digital biomarkers}, volume = {8}, number = {1}, pages = {22-29}, pmid = {39473802}, issn = {2504-110X}, abstract = {INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that alters gait and increases the risk of falls. The current model of care involves in-person multidisciplinary clinic visits to, in part, assess alterations in gait, evaluate safety, and make recommendations for management. Clinic visits, however, are relatively infrequent, and multidisciplinary evaluations can be physically demanding for patients. To better understand how gait changes over time in those with ALS and enable healthcare providers to properly respond to these changes, remote monitoring of functional mobility would be advantageous.

METHODS: The objective of this study was to remotely track long-term changes in walking speed using wearable inertial measurement units (IMUs). Nine ALS patients and 6 healthy controls submitted twice-weekly home walking recordings for 24 and 4 weeks, respectively. An IMU data processing method was developed and validated against laboratory-measured walking speed.

RESULTS: For both ALS patients and healthy controls, home walking speed was less than clinic walking speed by an average of 0.19 m/s (p = 0.0024). Over 24 weeks, home walking speed significantly decreased for 5 of 9 ALS patients at an average of -0.021 m/s/months (p = 0.005). Those who eventually transitioned to using assistive device (AD) while on the study demonstrated a greater decrease in walking speed than those who did not.

CONCLUSIONS: Remote longitudinal gait monitoring of ALS patients is feasible with the use of an IMU. Decreases in walking speed were detected in the majority of patients, most strongly in those who eventually transitioned to an AD. Home walking speed may more accurately represent the walking abilities of ALS patients in their real-life environments, a finding which further supports the case for remote monitoring in ALS.}, } @article {pmid39355053, year = {2023}, author = {Cortés Mancera, EA and Sinisterra Solis, FA and Romero-Castellanos, FR and Diaz-Meneses, IE and Kerik-Rotenberg, NE}, title = {[18]F-FDG PET/CT as a molecular biomarker in the diagnosis of amyotrophic lateral sclerosis associated with prostate cancer and progressive supranuclear palsy: A case report.}, journal = {Frontiers in nuclear medicine}, volume = {3}, number = {}, pages = {1137875}, pmid = {39355053}, issn = {2673-8880}, abstract = {INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative, multisystem disorder. Its clinical presentation typically consists of progressive focal muscle atrophy and weakness. In addition to motor disorders, the association between ALS and cancer has been researched, such as frontotemporal dementia and progressive supranuclear palsy. The diagnosis is based primarily on the clinical history, physical examination, electrodiagnostic tests (with an EMG needle), and neuroimaging, such as MRI and [18]F-FDG PET/CT.

PRESENTATION OF THE CASE: A 67-year-old male patient was diagnosed with prostate adenocarcinoma with a clinical picture of muscle weakness in the lower limbs that caused falls and was associated with fasciculations in the thighs and arms, alterations in the tone of voice, poor memory, and difficulty articulating words. In the neurological assessment, he described walking supported by a walker with decreased strength in both lower limbs and sensitivity without alterations. The diagnoses of upper and lower motor neuron disease and probable ALS were integrated. Furthermore, the probable coexistence of frontotemporal dementia/disorder (FDD) with ALS was considered. The main findings in the [18]F-FDG PET/CT study was hypometabolism in the cortex of the bilateral motor and premotor areas, the anterior cingulate, both caudate and putamen, a metabolic pattern compatible with ALS, and progressive supranuclear palsy.

CONCLUSION: Through the PET/CT studies, we demonstrated a case in which ALS, prostate cancer and progressive supranuclear palsy coexisted molecularly; it was clinically difficult to diagnose. Molecular imaging has potential in the diagnostic and prognostic evaluation of ALS. It is crucial to identify the disease early and reliably through metabolic patterns that allow us to confirm the disease or differentiate it from other pathologies.}, } @article {pmid39291146, year = {2023}, author = {Mathew, AM and Bhuvanendran, S and Nair, RS and K Radhakrishnan, A}, title = {Exploring the anti-inflammatory activities, mechanism of action and prospective drug delivery systems of tocotrienol to target neurodegenerative diseases.}, journal = {F1000Research}, volume = {12}, number = {}, pages = {338}, pmid = {39291146}, issn = {2046-1402}, abstract = {A major cause of death in the elderly worldwide is attributed to neurodegenerative diseases, such as AD (Alzheimer's disease), PD (Parkinson's disease), ALS (Amyotrophic lateral sclerosis), FRDA (Friedreich's ataxia), VaD (Vascular dementia) etc. These can be caused due to multiple factors such as genetic, physiological problems like stroke or tumor, or even external causes like viruses, toxins, or chemicals. T3s (tocotrienols) exhibit various bioactive properties where it acts as an antioxidant, anti-inflammatory, anti-tumorigenic, and cholesterol lowering agent. Since T3 interferes with and influences several anti-inflammatory mechanisms, it aids in combating inflammatory responses that lead to disease progression. T3s are found to have a profound neuroprotective ability, however, due to their poor oral bioavailability, their full potential could not be exploited. Hence there is a need to explore other drug delivery techniques, especially focusing on aspects of nanotechnology. In this review paper we explore the anti-inflammatory mechanisms of T3 to apply it in the treatment of neurodegenerative diseases and also discusses the possibilities of nano methods of administering tocotrienols to target neurodegenerative diseases.}, } @article {pmid39165755, year = {2023}, author = {Bustos, LM and Sattler, R}, title = {The Fault in Our Astrocytes - cause or casualties of proteinopathies of ALS/FTD and other neurodegenerative diseases?.}, journal = {Frontiers in molecular medicine}, volume = {3}, number = {}, pages = {1075805}, pmid = {39165755}, issn = {2674-0095}, support = {R21 NS125861/NS/NINDS NIH HHS/United States ; }, abstract = {Many neurodegenerative diseases fall under the class of diseases known as proteinopathies, whereby the structure and localization of specific proteins become abnormal. These aberrant proteins often aggregate within cells which disrupts vital homeostatic and physiological cellular functions, ultimately contributing to cell death. Although neurodegenerative disease research is typically neurocentric, there is evidence supporting the role of non-neuronal cells in the pathogenesis of these diseases. Specifically, the role of astrocytes in neurodegenerative diseases has been an ever-growing area of research. Astrocytes are one of the most abundant cell types in the central nervous system (CNS) and provide an array of essential homeostatic functions that are disrupted in neurodegenerative diseases. Astrocytes can exhibit a reactive phenotype that is characterized by molecular changes, as well as changes in morphology and function. In neurodegenerative diseases, there is potential for reactive astrocytes to assume a loss-of-function phenotype in homeostatic operations such as synapse maintenance, neuronal metabolic support, and facilitating cell-cell communication between glia and neurons. They are also able to concurrently exhibit gain-of-function phenotypes that can be destructive to neural networks and the astrocytes themselves. Additionally, astrocytes have been shown to internalize disease related proteins and reflect similar or exacerbated pathology that has been observed in neurons. Here, we review several major neurodegenerative disease-specific proteinopathies and what is known about their presence in astrocytes and the potential consequences regarding cell and non-cell autonomous neurodegeneration.}, } @article {pmid39281332, year = {2022}, author = {Kirikae, H and Harada, R and Hosaka, T and Misu, T and Ando, D and Warita, H and Endo, T and Sonobe, S and Niizuma, K and Aoki, M}, title = {Case Report: Vertebro-vertebral arteriovenous fistula showing symptoms mimicking ALS: Diagnostic imaging supports accurate differentiation between ALS and mimicking conditions.}, journal = {F1000Research}, volume = {11}, number = {}, pages = {546}, pmid = {39281332}, issn = {2046-1402}, abstract = {We report a rare case of a vertebro-vertebral arteriovenous fistula (VVAVF) manifesting as amyotrophic lateral sclerosis (ALS). A 76-year-old female patient presented with progressive weakness, muscle atrophy, fasciculation, and preserved deep tendon reflexes in the right upper limb. Electrophysiological testing showed lower motor neuron dysfunction. The patient was suspected to have ALS, but cervical magnetic resonance imaging (MRI) revealed enlarged blood vessels in the spinal canal, which compressed the cervical spinal cord and nerve roots. Angiography showed a shunt from the right vertebral artery to the right intervertebral vein and the vertebral venous plexus; therefore, the patient was diagnosed with VVAVF. Transarterial embolization was performed to obliterate the shunt, and weakness in the patient's right upper limb subsequently improved. It is worth considering VVAVF as a differential diagnosis of ALS-like diseases.}, } @article {pmid39484675, year = {2022}, author = {Chopra, N and Menounos, S and Choi, JP and Hansbro, PM and Diwan, AD and Das, A}, title = {Blood-Spinal Cord Barrier: Its Role in Spinal Disorders and Emerging Therapeutic Strategies.}, journal = {NeuroSci}, volume = {3}, number = {1}, pages = {1-27}, pmid = {39484675}, issn = {2673-4087}, abstract = {The blood-spinal cord barrier (BSCB) has been long thought of as a functional equivalent to the blood-brain barrier (BBB), restricting blood flow into the spinal cord. The spinal cord is supported by various disc tissues that provide agility and has different local immune responses compared to the brain. Though physiologically, structural components of the BSCB and BBB share many similarities, the clinical landscape significantly differs. Thus, it is crucial to understand the composition of BSCB and also to establish the cause-effect relationship with aberrations and spinal cord dysfunctions. Here, we provide a descriptive analysis of the anatomy, current techniques to assess the impairment of BSCB, associated risk factors and impact of spinal disorders such as spinal cord injury (SCI), amyotrophic lateral sclerosis (ALS), peripheral nerve injury (PNI), ischemia reperfusion injury (IRI), degenerative cervical myelopathy (DCM), multiple sclerosis (MS), spinal cavernous malformations (SCM) and cancer on BSCB dysfunction. Along with diagnostic and mechanistic analyses, we also provide an up-to-date account of available therapeutic options for BSCB repair. We emphasize the need to address BSCB as an individual entity and direct future research towards it.}, } @article {pmid39091724, year = {2024}, author = {Lv, G and Sayles, NM and Huang, Y and Mancinelli, CD and McAvoy, K and Shneider, NA and Manfredi, G and Kawamata, H and Eliezer, D}, title = {Amyloid fibril structures link CHCHD10 and CHCHD2 to neurodegeneration.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {39091724}, issn = {2692-8205}, support = {P30 CA016087/CA/NCI NIH HHS/United States ; RF1 AG066493/AG/NIA NIH HHS/United States ; S10 OD028556/OD/NIH HHS/United States ; U01 NS134684/NS/NINDS NIH HHS/United States ; R35 NS122209/NS/NINDS NIH HHS/United States ; S10 OD016320/OD/NIH HHS/United States ; F31 HL154651/HL/NHLBI NIH HHS/United States ; F31 AG077836/AG/NIA NIH HHS/United States ; }, abstract = {CHCHD10 is mutated in rare cases of FTD and ALS and aggregates in mouse models of disease. Here we show that the disordered N-terminal domain of CHCHD10 forms amyloid fibrils and report their cryoEM structure. Disease-associated mutations cannot be accommodated by the WT fibril structure, while sequence differences between CHCHD10 and CHCHD2 are tolerated, explaining the co-aggregation of the two proteins and linking CHCHD10 and CHCHD2 amyloid fibrils to neurodegeneration.}, } @article {pmid39091345, year = {2024}, author = {Hernández, CA and Peikert, K and Qiao, M and Darras, A and de Wilde, JRA and Bos, J and Leibowitz, M and Galea, I and Wagner, C and Rab, MAE and Walker, RH and Hermann, A and van Beers, EJ and van Wijk, R and Kaestner, L}, title = {Osmotic gradient ektacytometry - a novel diagnostic approach for neuroacanthocytosis syndromes.}, journal = {Frontiers in neuroscience}, volume = {18}, number = {}, pages = {1406969}, pmid = {39091345}, issn = {1662-4548}, abstract = {INTRODUCTION: The unique red blood cell (RBC) properties that characterize the rare neuroacanthocytosis syndromes (NAS) have prompted the exploration of osmotic gradient ektacytometry (Osmoscan) as a diagnostic tool for these disorders. In this exploratory study, we assessed if Osmoscans can discriminate NAS from other neurodegenerative diseases.

METHODS: A comprehensive assessment was conducted using Osmoscan on a diverse group of patients, including healthy controls (n = 9), neuroacanthocytosis syndrome patients (n = 6, 2 VPS13A and 4 XK disease), Parkinson's disease patients (n = 6), Huntington's disease patients (n = 5), and amyotrophic lateral sclerosis patients (n = 4). Concurrently, we collected and analyzed RBC indices and patients' characteristics.

RESULTS: Statistically significant changes were observed in NAS patients compared to healthy controls and other conditions, specifically in osmolality at minimal elongation index (Omin), maximal elongation index (EImax), the osmolality at half maximal elongation index in the hyperosmotic part of the curve (Ohyper), and the width of the curve close to the osmolality at maximal elongation index (Omax-width).

DISCUSSION: This study represents an initial exploration of RBC properties from NAS patients using osmotic gradient ektacytometry. While specific parameters exhibited differences, only Ohyper and Omax-width yielded 100% specificity for other neurodegenerative diseases. Moreover, unique correlations between Osmoscan parameters and RBC indices in NAS versus controls were identified, such as osmolality at maximal elongation index (Omax) vs. mean cellular hemoglobin content (MCH) and minimal elongation index (EImin) vs. red blood cell distribution width (RDW). Given the limited sample size, further studies are essential to establish diagnostic guidelines based on these findings.}, } @article {pmid39091344, year = {2024}, author = {Goffin, L and Lemoine, D and Clotman, F}, title = {Potential contribution of spinal interneurons to the etiopathogenesis of amyotrophic lateral sclerosis.}, journal = {Frontiers in neuroscience}, volume = {18}, number = {}, pages = {1434404}, pmid = {39091344}, issn = {1662-4548}, abstract = {Amyotrophic lateral sclerosis (ALS) consists of a group of adult-onset fatal and incurable neurodegenerative disorders characterized by the progressive death of motor neurons (MNs) throughout the central nervous system (CNS). At first, ALS was considered to be an MN disease, caused by cell-autonomous mechanisms acting specifically in MNs. Accordingly, data from ALS patients and ALS animal models revealed alterations in excitability in multiple neuronal populations, including MNs, which were associated with a variety of cellular perturbations such as protein aggregation, ribonucleic acid (RNA) metabolism defects, calcium dyshomeostasis, modified electrophysiological properties, and autophagy malfunctions. However, experimental evidence rapidly demonstrated the involvement of other types of cells, including glial cells, in the etiopathogenesis of ALS through non-cell autonomous mechanisms. Surprisingly, the contribution of pre-motor interneurons (INs), which regulate MN activity and could therefore critically modulate their excitability at the onset or during the progression of the disease, has to date been severely underestimated. In this article, we review in detail how spinal pre-motor INs are affected in ALS and their possible involvement in the etiopathogenesis of the disease.}, } @article {pmid39091255, year = {2024}, author = {Roggenbuck, J and Kaschalk, M and Eustace, R and Vicini, L and Gokun, Y and Harms, MB and Kolb, SJ}, title = {The Answer ALS return of results study: Answering the duty to disclose.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {25}, number = {7-8}, pages = {743-750}, doi = {10.1080/21678421.2024.2385004}, pmid = {39091255}, issn = {2167-9223}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/diagnosis/psychology ; Male ; Female ; Middle Aged ; *Genetic Testing/methods ; *Disclosure ; Aged ; Adult ; Prospective Studies ; }, abstract = {Objective: The Return of Answer ALS Results (RoAR) Study was designed to provide a mechanism for participants in Answer ALS, a large, prospectively designed natural history and biorepository study to receive select clinical genetic testing results and study participants' experience with the results disclosure. Methods: Participants consented to receive results of five ALS genes (C9orf72, SOD1, FUS, TARDP, TBK1) and/or 59 medically actionable genes as designated by the American College of Medical Genetics. Patient-reported genetic testing outcomes were measured via a post-disclosure survey. Results: Of 645 eligible Answer ALS enrollees, 143 (22%) enrolled and completed participation in RoAR. Pathogenic variants were identified in 22/143 (15.4%) participants, including 13/143 (9.0%) in ALS genes and 9/143 (6.3%) in ACMG genes. Participant-reported measures of result utility indicated the research result disclosure was as or more successful than published patient-reported outcomes of result disclosure the clinical setting. Conclusions: This study serves as a model of a "disclosure study" to share results from genomic research with participants who were not initially offered the option to receive results, and our findings can inform the design of future, large scale genomic projects to empower research participants to access their genetic information.}, } @article {pmid39091098, year = {2025}, author = {Annetta, MG and Barbato, G and Pisciaroli, E and Marche, B and Sabatelli, M and Pittiruti, M}, title = {Central venous catheter-related thrombosis in patients with amyotrophic lateral sclerosis.}, journal = {The journal of vascular access}, volume = {26}, number = {4}, pages = {1180-1186}, doi = {10.1177/11297298241262821}, pmid = {39091098}, issn = {1724-6032}, mesh = {Humans ; Retrospective Studies ; *Catheterization, Central Venous/adverse effects/instrumentation ; Male ; Female ; Middle Aged ; Risk Factors ; Aged ; *Amyotrophic Lateral Sclerosis/diagnosis/complications ; *Central Venous Catheters ; *Catheterization, Peripheral/adverse effects/instrumentation ; Quadriplegia/diagnosis ; Time Factors ; Adult ; Paraplegia/diagnosis/complications ; *Upper Extremity Deep Vein Thrombosis/etiology/prevention & control/diagnostic imaging ; Risk Assessment ; Treatment Outcome ; Catheters, Indwelling ; }, abstract = {BACKGROUND: Central venous catheterization may be required in patients with amyotrophic lateral sclerosis (ALS) for parenteral nutrition, antibiotic treatment, or blood sampling. Different venous access devices can be taken into consideration-centrally inserted central catheters (CICC), peripherally inserted central catheters (PICC), and femorally inserted central catheters (FICCs)-depending on the clinical conditions of the patients. Regardless of the type of access, the presence of paraplegia or tetraplegia is commonly considered a risk factor for catheter-related thrombosis (CRT).

METHOD: This retrospective study analyzes the rate of CRT and other non-infectious complications associated with central venous access in a cohort of 115 patients with paraplegia or tetraplegia, most of them affected by ALS (n = 109).

RESULTS: In a period of 34 months, from January 2021 to October 2023, we inserted 75 FICCs, 29 CICCs, and 11 PICCs. PICCs were inserted only in patients with preserved motility of the upper limbs. All devices were inserted by trained operators adopting appropriate insertion bundles. We had no immediate or early complication. Though antithrombotic prophylaxis was adopted only in 61.7% of patients, we had no symptomatic CRT. Other non-infectious complications were infrequent (4 out of 115 patients).

CONCLUSION: These results suggest (a) that the presence of paraplegia or tetraplegia is not necessarily associated with an increased risk of CRT, (b) that the adoption of well-designed insertion bundles plays a key role in minimizing non-infectious complications, and (c) that the insertion of FICCs by direct cannulation of the superficial femoral vein at mid-thigh in paraplegic/tetraplegic patients may have the same advantages which have been described in the general population.}, } @article {pmid39088455, year = {2024}, author = {Bonthron, C and Burley, S and Broadhead, MJ and Metodieva, V and Grant, SGN and Chandran, S and Miles, GB}, title = {Excitatory to inhibitory synaptic ratios are unchanged at presymptomatic stages in multiple models of ALS.}, journal = {PloS one}, volume = {19}, number = {8}, pages = {e0306423}, pmid = {39088455}, issn = {1932-6203}, mesh = {*Amyotrophic Lateral Sclerosis/pathology/physiopathology/metabolism/genetics ; Animals ; *Astrocytes/metabolism/pathology ; Mice ; *Disease Models, Animal ; *Coculture Techniques ; *Synapses/metabolism/physiology ; *Motor Neurons/metabolism/pathology/physiology ; *Spinal Cord/metabolism/pathology ; Humans ; Excitatory Postsynaptic Potentials ; Mice, Transgenic ; Cells, Cultured ; Synaptic Transmission ; }, abstract = {Hyperexcitability of motor neurons and spinal cord motor circuitry has been widely reported in the early stages of Amyotrophic Lateral Sclerosis (ALS). Changes in the relative amount of excitatory to inhibitory inputs onto a neuron (E:I synaptic ratio), possibly through a developmental shift in synapse formation in favour of excitatory transmission, could underlie pathological hyperexcitability. Given that astrocytes play a major role in early synaptogenesis and are implicated in ALS pathogenesis, their potential contribution to disease mechanisms involving synaptic imbalances and subsequent hyperexcitability is also of great interest. In order to assess E:I ratios in ALS, we utilised a novel primary spinal neuron / astrocyte co-culture system, derived from neonatal mice, in which synapses are formed in vitro. Using multiple ALS mouse models we found that no combination of astrocyte or neuron genotype produced alterations in E:I synaptic ratios assessed using pre- and post-synaptic anatomical markers. Similarly, we observed that ephrin-B1, a major contact-dependent astrocytic synaptogenic protein, was not differentially expressed by ALS primary astrocytes. Further to this, analysis of E:I ratios across the entire grey matter of the lumbar spinal cord in young (post-natal day 16-19) ALS mice revealed no differences versus controls. Finally, analysis in co-cultures of human iPSC-derived motor neurons and astrocytes harbouring the pathogenic C9orf72 hexanucleotide repeat expansion showed no evidence of a bias toward excitatory versus inhibitory synapse formation. We therefore conclude, utilising multiple ALS models, that we do not observe significant changes in the relative abundance of excitatory versus inhibitory synapses as would be expected if imbalances in synaptic inputs contribute to early hyperexcitability.}, } @article {pmid39088003, year = {2024}, author = {Lai, HJ and Kuo, YC and Ting, CH and Yang, CC and Kao, CH and Tsai, YC and Chao, CC and Hsueh, HW and Hsieh, PF and Chang, HY and Wang, IF and Tsai, LK}, title = {Increase of HCN current in SOD1-associated amyotrophic lateral sclerosis.}, journal = {Brain : a journal of neurology}, volume = {147}, number = {12}, pages = {4240-4253}, doi = {10.1093/brain/awae248}, pmid = {39088003}, issn = {1460-2156}, support = {108-2314-B-002-082-MY3//Ministry of Science and Technology, ROC/ ; MQ999//National Taiwan University Hospital/ ; 112-BIH001//National Taiwan University Hospital Hsinchu branch/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/genetics/metabolism ; Humans ; Animals ; *Superoxide Dismutase-1/genetics ; Mice ; Male ; Female ; *Mice, Transgenic ; *Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels/genetics/metabolism ; Middle Aged ; Aged ; Axons/metabolism ; Disease Models, Animal ; Potassium Channels/metabolism/genetics ; Adult ; }, abstract = {The clinical manifestations of sporadic amyotrophic lateral sclerosis (ALS) vary widely. However, the current classification of ALS is based mainly on clinical presentations, and the roles of electrophysiological and biomedical biomarkers remain limited. Herein, we investigated a group of patients with sporadic ALS and an ALS mouse model with superoxide dismutase 1 (SOD1)/G93A transgenes using nerve excitability tests (NETs) to investigate axonal membrane properties and chemical precipitation, followed by ELISA analysis to measure plasma misfolded protein levels. Six of 19 patients (31.6%) with sporadic ALS had elevated plasma misfolded SOD1 protein levels. In sporadic ALS patients, only those with elevated misfolded SOD1 protein levels showed an increased inward rectification in the current-voltage threshold curve and an increased threshold reduction in the hyperpolarizing threshold electrotonus in the NET study. Two familial ALS patients with SOD1 mutations also exhibited similar electrophysiological patterns of NET. For patients with sporadic ALS showing significantly increased inward rectification in the current-voltage threshold curve, we noted an elevation in plasma misfolded SOD1 level, but not in total SOD1, misfolded C9orf72 or misfolded phosphorylated TDP43 levels. Computer simulations demonstrated that the aforementioned axonal excitability changes are likely to be associated with an increase in hyperpolarization-activated cyclic nucleotide-gated (HCN) current. In SOD1/G93A mice, NET also showed an increased inward rectification in the current-voltage threshold curve, which could be reversed by a single injection of the HCN channel blocker, ZD7288. Daily treatment of SOD1/G93A mice with ZD7288 partly prevented the early motor function decline and spinal motor neuron death. In summary, sporadic ALS patients with elevated plasma misfolded SOD1 exhibited similar patterns of motor axonal excitability changes to familial ALS patients and ALS mice with mutant SOD1, suggesting the existence of SOD1-associated sporadic ALS. The observed NET pattern of increased inward rectification in the current-voltage threshold curve was attributable to an elevation in the HCN current in SOD1-associated ALS.}, } @article {pmid39087137, year = {2024}, author = {Chisthi, MM}, title = {Unveiling the potential of electrocautery-enhanced lumen-apposing metal stents in endoscopic ultrasound-guided biliary drainage.}, journal = {World journal of gastrointestinal surgery}, volume = {16}, number = {7}, pages = {1956-1959}, pmid = {39087137}, issn = {1948-9366}, abstract = {This editorial delves into Peng et al's article, published in the World Journal of Gastrointestinal Surgery. Peng et al's meta-analysis investigates the effectiveness of electrocautery-enhanced lumen-apposing metal stents (ECE-LAMS) in ultrasound-guided biliary drainage for alleviating malignant biliary obstruction. Examining 14 studies encompassing 620 participants, the research underscores a robust technical success rate of 96.7%, highlighting the efficacy of ECE-LAMS, particularly in challenging cases which have failed endoscopic retrograde cholangio pancreatography. A clinical success rate of 91.0% underscores its impact on symptom alleviation, while a reasonably tolerable adverse event rate of 17.5% is observed. However, the 7.3% re-intervention rate stresses the need for post-procedural monitoring. Subgroup analyses validate consistent outcomes, bolstering the applicability of ECE-LAMS. These findings advocate for the adoption of ECE-LAMS as an appropriate approach for biliary palliation, urging further exploration in real-world clinical contexts. They offer valuable insights for optimizing interventions targeting malignant biliary obstruction management.}, } @article {pmid39086926, year = {2024}, author = {Tilliole, P and Fix, S and Godin, JD}, title = {hnRNPs: roles in neurodevelopment and implication for brain disorders.}, journal = {Frontiers in molecular neuroscience}, volume = {17}, number = {}, pages = {1411639}, pmid = {39086926}, issn = {1662-5099}, abstract = {Heterogeneous nuclear ribonucleoproteins (hnRNPs) constitute a family of multifunctional RNA-binding proteins able to process nuclear pre-mRNAs into mature mRNAs and regulate gene expression in multiple ways. They comprise at least 20 different members in mammals, named from A (HNRNP A1) to U (HNRNP U). Many of these proteins are components of the spliceosome complex and can modulate alternative splicing in a tissue-specific manner. Notably, while genes encoding hnRNPs exhibit ubiquitous expression, increasing evidence associate these proteins to various neurodevelopmental and neurodegenerative disorders, such as intellectual disability, epilepsy, microcephaly, amyotrophic lateral sclerosis, or dementias, highlighting their crucial role in the central nervous system. This review explores the evolution of the hnRNPs family, highlighting the emergence of numerous new members within this family, and sheds light on their implications for brain development.}, } @article {pmid39086672, year = {2023}, author = {Pasinelli, P and Meyer, K and Ferraiuolo, L and Culibrk, RA and Sattler, R}, title = {Editorial: The role of glial cells in neurodegeneration.}, journal = {Frontiers in molecular medicine}, volume = {3}, number = {}, pages = {1337286}, doi = {10.3389/fmmed.2023.1337286}, pmid = {39086672}, issn = {2674-0095}, support = {T32 AG044402/AG/NIA NIH HHS/United States ; }, } @article {pmid39086635, year = {2024}, author = {Pérez-Holanda, S}, title = {Non-participation of asymptomatic candidates in screening protocols reduces early diagnosis and worsens prognosis of colorectal cancer.}, journal = {World journal of gastroenterology}, volume = {30}, number = {26}, pages = {3198-3200}, pmid = {39086635}, issn = {2219-2840}, mesh = {Humans ; *Colorectal Neoplasms/diagnosis ; *Early Detection of Cancer/methods/statistics & numerical data ; Prognosis ; Asymptomatic Diseases ; Mass Screening/methods/statistics & numerical data ; Japan/epidemiology ; Neoplasm Staging ; Colonoscopy/statistics & numerical data ; }, abstract = {The Agatsuma et al's study shows that despite the evidence of the benefits of an early colorectal cancer (CRC) diagnosis, through screening in asymptomatic subjects, up to 50% of candidates reject this option and many of those affected are diagnosed later, in advanced stages. The efficacy of screening programs has been well-established for several years, which reduces the risk of CRC morbidity and mortality, without taking into account the test used for screening, or other tools. Nevertheless, a significant proportion of patients remain unscreened, so understanding the factors involved, as well as the barriers of the population to adherence is the first step to possibly modify the participation rate. These barriers could include a full range of social and political aspects, especially the type of financial provision of each health service. In Japan, health services are universal, and this advantageous situation makes it easier for citizens to access to these services, contributing to the detection of various diseases, including CRC. Interestingly, the symptomatic CRC group had a lower early-stage diagnosis rate than the patients detected during follow-up for other comorbidities, and symptomatic and cancer screening groups showed similar early-stage diagnosis.}, } @article {pmid39086545, year = {2024}, author = {Carrera-Juliá, S and Obrador, E and López-Blanch, R and Oriol-Caballo, M and Moreno-Murciano, P and Estrela, JM}, title = {Ketogenic effect of coconut oil in ALS patients.}, journal = {Frontiers in nutrition}, volume = {11}, number = {}, pages = {1429498}, pmid = {39086545}, issn = {2296-861X}, abstract = {A recent pilot study in amyotrophic lateral sclerosis (ALS) patients analyzed the effect of a Mediterranean diet (MeDi) supplemented with nicotinamide riboside (NR, a NAD[+] promoter), pterostilbene (PTER, a natural antioxidant) and/or coconut oil on anthropometric variables in ALS patients. The results suggested that the MeDi supplemented with NR, PTER and coconut oil is the nutritional intervention showing the greatest benefits at anthropometric levels. Over the last 30 years, glucose intolerance has been reported in ALS patients. Thus, suggesting that an alternative source of energy may be preferential for motor neurons to survive. Ketone bodies (KBs), provided through a MeDi with a lower carbohydrate content but enriched with medium chain triglycerides, could be a therapeutic alternative to improve the neuromotor alterations associated with the disease. Nevertheless, the use of a coconut oil-supplemented diet, as potentially ketogenic, is a matter of controversy. In the present report we show that a MeDi supplemented with coconut oil increases the levels of circulating KBs in ALS patients.}, } @article {pmid39086006, year = {2024}, author = {An, TJ and Jang, S and Hering, K and Vazquez, R and Scalia, J and Berry, JD and Kalva, SP and Arellano, RS}, title = {Gastrostomy placement in patients with amyotrophic lateral sclerosis: assessment of risk factors for post-procedural respiratory failure.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {25}, number = {7-8}, pages = {680-686}, doi = {10.1080/21678421.2024.2384994}, pmid = {39086006}, issn = {2167-9223}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/complications/surgery ; *Gastrostomy/methods ; Male ; Female ; Middle Aged ; Aged ; Retrospective Studies ; *Respiratory Insufficiency/etiology ; Risk Factors ; Adult ; Aged, 80 and over ; Deglutition Disorders/etiology/epidemiology ; }, abstract = {OBJECTIVE: Radiologically inserted gastrostomy placement may be performed in patients with dysphagia secondary to amyotrophic lateral sclerosis (ALS). This study assessed technical outcomes and complications related to gastrostomy placement in patients with ALS.

METHODS: A retrospective review of patients with ALS who underwent gastrostomy placement between 2021 and 2023 was performed. Patient demographics, medical history, ALS disease manifestations, survival, and post-procedural complications were obtained from the electronic medical record. Technical outcomes related to gastrostomy placement were obtained from operative notes and review of procedural imaging.

RESULTS: A total of 100 patients were included in the study. The mean duration of ALS diagnosis at time of gastrostomy placement was 1.3 +/-1.2 years. The mean slow vital capacity at time of gastrostomy placement was 54.0 +/-20.2% (range 10-155%). Technical success was 100%, with 91 placed using fluoroscopic guidance and 9 placed with computed tomography guidance. Eighty-three percent of gastrostomies were performed as outpatient procedures, while 17/100 patients were admitted following the procedure for monitoring. Post-procedural adverse events were noted in 21/100 patients (15 mild and 6 moderate or greater). Three patients developed respiratory failure after gastrostomy tube placement and died within 1-week post-procedure. Lower pre-procedural slow vital capacity was associated with higher risk of post-procedural respiratory failure (p = 0.0003*).

CONCLUSIONS: Gastrostomy placement in patients with ALS has a high technical success rate and may be performed safely in the outpatient setting in appropriate patients. Patients with low slow vital capacity related to ALS should be admitted post-procedurally for airway monitoring and support.}, } @article {pmid39085618, year = {2024}, author = {Müller, KJ and Schmidbauer, ML and Schönecker, S and Kamm, K and Pelz, JO and Holzapfel, K and Papadopoulou, M and Bakola, E and Tsivgoulis, G and Naumann, M and Hermann, A and Walter, U and Dimitriadis, K and Reilich, P and Schöberl, F}, title = {Diagnostic accuracy and confounders of vagus nerve ultrasound in amyotrophic lateral sclerosis-a single-center case series and pooled individual patient data meta-analysis.}, journal = {Journal of neurology}, volume = {271}, number = {9}, pages = {6255-6263}, pmid = {39085618}, issn = {1432-1459}, support = {DFG TRR 338//Deutsche Forschungsgemeinschaft/ ; DFG TRR 274//Deutsche Forschungsgemeinschaft/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/diagnostic imaging/diagnosis ; Humans ; Male ; Aged ; Female ; Middle Aged ; *Ultrasonography ; *Vagus Nerve/diagnostic imaging ; }, abstract = {BACKGROUND: Several single-center studies proposed utility of vagus nerve (VN) ultrasound for detecting disease severity, autonomic dysfunction, and bulbar phenotype in amyotrophic lateral sclerosis (ALS). However, the resulting body of literature shows opposing results, leaving considerable uncertainty on the clinical benefits of VN ultrasound in ALS.

METHODS: Relevant studies were identified up to 04/2024 and individual patient data (IPD) obtained from the respective authors were pooled with a so far unpublished cohort (from Munich). An IPD meta-analysis of 109 patients with probable or definite ALS (El Escorial criteria) and available VN cross-sectional area (CSA) was performed, with age, sex, ALS Functional Rating Scale-revised (ALSFRS-R), disease duration, and bulbar phenotype as independent variables.

RESULTS: Mean age was 65 years (± 12) and 47% of patients (± 12) had bulbar ALS. Mean ALSFRS-R was 38 (± 7), and mean duration was 18 months (± 18). VN atrophy was highly prevalent [left: 67% (± 5), mean CSA 1.6mm[2] (± 0.6); right: 78% (± 21), mean CSA 1.8 mm[2] (± 0.7)]. VN CSA correlated with disease duration (mean slope: left - 0.01; right - 0.01), but not with ALSFRS-R (mean slope: left 0.004; mean slope: right - 0.002). Test accuracy for phenotyping bulbar vs. non-bulbar ALS was poor (summary receiver operating characteristic area under the curve: left 0.496; right 0.572).

CONCLUSION: VN atrophy in ALS is highly prevalent and correlates with disease duration, but not with ALSFRS-R. VN CSA is insufficient to differentiate bulbar from non-bulbar ALS phenotypes. Further studies are warranted to analyze the link between VN atrophy, autonomic impairment, and survival in ALS.}, } @article {pmid39084789, year = {2024}, author = {Wang, H and Zhang, Y and Ren, Y and Liu, Y and Feng, Z and Dong, L}, title = {Mechanism of multiple resistance to fenoxaprop-P-ethyl, mesosulfuron-methyl, and isoproturon in Avena fatua L. from China.}, journal = {Pesticide biochemistry and physiology}, volume = {203}, number = {}, pages = {105985}, doi = {10.1016/j.pestbp.2024.105985}, pmid = {39084789}, issn = {1095-9939}, mesh = {*Herbicide Resistance/genetics ; *Herbicides/pharmacology ; *Oxazoles/pharmacology ; China ; *Phenylurea Compounds/pharmacology ; *Acetyl-CoA Carboxylase/genetics/metabolism ; *Propionates/pharmacology ; *Acetolactate Synthase/genetics/metabolism ; Poaceae/drug effects ; Phenylpropionates/pharmacology ; Plant Proteins/genetics/metabolism ; Sulfonylurea Compounds ; }, abstract = {Avena fatua L. is one of the most damaging and malignant weeds in wheat fields in China. Fenoxaprop-P-ethyl, mesosulfuron-methyl, and isoproturon, which belong to Acetyl-CoA carboxylase- (ACCase), acetolactate synthase- (ALS), and photosystem II- (PS II) inhibitors, respectively, are commonly used in wheat fields and have a long history of use on A. fatua. An A. fatua population (R) resistant to fenoxaprop-P-ethyl, mesosulfuron-methyl, and isoproturon was collected from a wheat field in 2020. This study explored the mechanisms of target site resistance (TSR) and non-target site resistance (NTSR) in the multi-resistant A. fatua. Whole-plant bioassays showed that the R population had evolved high resistance to fenoxaprop-P-ethyl and moderate resistance to mesosulfuron-methyl and isoproturon. However, no mutations were detected in the ACCase, ALS, or psbA genes in the R population. In addition, the ACCase and ALS gene expression levels in the R group were significantly higher than those in the susceptible population (S) after treatment with fenoxaprop-P-ethyl or mesosulfuron-methyl. In vitro ACCase and ALS activity assays showed that ACCase and ALS from the R population were insensitive to fenoxaprop and mesosulfuron-methyl, respectively, with resistance indices 6.12-fold and 17.46-fold higher than those of the S population. Furthermore, pretreatment with P450 inhibitors significantly (P < 0.05) reversed the multi-resistant A. fatua's resistance to fenoxaprop-P-ethyl, mesosulfuron-methyl, and isoproturon. Sethoxydim, flucarbazone‑sodium, chlortoluron, and cypyrafluone were effective in controlling multi-resistance A. fatua. Therefore, the overexpression of ACCase and ALS to synthesize sufficient herbicide-targeting proteins, along with P450-mediated metabolism, conferred resistance to fenoxaprop-P-ethyl, mesosulfuron-methyl, and isoproturon in the R population.}, } @article {pmid39084788, year = {2024}, author = {Ohta, K and Kawamata, E and Hori, T and Sada, Y}, title = {Connecting genes to whole plants in dilution effect of target-site ALS inhibitor resistance of Schoenoplectiella juncoides (Roxb.) Lye (Cyperaceae).}, journal = {Pesticide biochemistry and physiology}, volume = {203}, number = {}, pages = {105984}, doi = {10.1016/j.pestbp.2024.105984}, pmid = {39084788}, issn = {1095-9939}, mesh = {*Acetolactate Synthase/genetics/metabolism/antagonists & inhibitors ; *Herbicide Resistance/genetics ; *Herbicides/pharmacology ; *Cyperaceae/genetics/drug effects ; Plant Proteins/genetics/metabolism ; Gene Expression Regulation, Plant/drug effects ; Mutation ; Genes, Plant ; }, abstract = {This study focuses on dilution effect of target-site resistance (TSR) to acetolactate synthase (ALS) inhibitors in Schoenoplectiella juncoides, which harbors two ALS genes, ALS1 and ALS2. We assessed gene expression, enzyme activity, and whole-plant resistance profiles across four S. juncoides lines: the susceptible line, the parental resistant lines with a homozygous mutation in either ALS1 or ALS2, and the bred progeny line with homozygous mutations in both ALS1 and ALS2. Gene expression and enzyme function showed a proportional relationship that the expression ratios of ALS1 to ALS2, approximately 70:30, were consistent with the functional ratio predicted by the double-sigmoidal plateau positions observed in enzyme assays. However, at the whole-plant level, resistance did not correlate to the putative abundance of susceptible enzyme, but the parental lines showed similar resistance to each other despite different enzyme-level resistances. This suggests a non-proportional mechanism in the reflection of physiological enzymatic profiles to whole-plant resistance profiles. These findings highlight the complexity of herbicide resistance and the need for further research to understand the mechanisms that influence resistance outcomes. Understanding these relationships is essential for developing strategies to manage herbicide resistance effectively.}, } @article {pmid39084570, year = {2024}, author = {Liu, J and Zhao, W and Guo, J and Kang, K and Li, H and Yang, X and Li, J and Wang, Q and Qiao, H}, title = {Electroacupuncture alleviates motor dysfunction by regulating neuromuscular junction disruption and neuronal degeneration in SOD1[G93A] mice.}, journal = {Brain research bulletin}, volume = {216}, number = {}, pages = {111036}, doi = {10.1016/j.brainresbull.2024.111036}, pmid = {39084570}, issn = {1873-2747}, mesh = {Animals ; *Electroacupuncture/methods ; *Neuromuscular Junction/pathology/metabolism ; *Motor Neurons/pathology/physiology ; *Mice, Transgenic ; Mice ; *Amyotrophic Lateral Sclerosis/therapy/pathology/genetics ; Disease Models, Animal ; Male ; Nerve Degeneration/therapy/pathology ; Muscle, Skeletal/pathology ; Superoxide Dismutase-1/genetics/metabolism ; Sciatic Nerve/injuries/pathology ; Mice, Inbred C57BL ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurological disease characterized by the progressive destruction of the neuromuscular junction (NMJ) and the degeneration of motor neurons, eventually leading to atrophy and paralysis of voluntary muscles responsible for motion and breathing. NMJs, synaptic connections between motor neurons and skeletal muscle fibers, are extremely fragile in ALS. To determine the effects of early electroacupuncture (EA) intervention on nerve reinnervation and regeneration following injury, a model of sciatic nerve injury (SNI) was first established using SOD1[G93A] mice, and early electroacupuncture (EA) intervention was conducted at Baihui (DU20), and bilateral Zusanli (ST36). The results revealed that EA increased the Sciatic nerve Functional Index, the structural integrity of the gastrocnemius muscles, and the cross-sectional area of muscle fibers, as well as up-regulated the expression of acetylcholinesterase and facilitated the co-location of α7 nicotinic acetate choline receptors and α-actinin. Overall, these results suggested that EA can promote the repair and regeneration of injured nerves and delay NMJ degeneration in SOD1[G93A]-SNI mice. Moreover, analysis of the cerebral cortex demonstrated that EA alleviated cortical motor neuron damage in SOD1[G93A] mice, potentially attributed to the inhibition of the cyclic GMP-AMP synthase-stimulator of interferon genes pathway and the release of interferon-β suppressing the activation of natural killer cells and the secretion of interferon-γ, thereby further inhibiting microglial activation and the expression of inflammatory factors. In summary, EA delayed the degeneration of NMJ and mitigated the loss of cortical motor neurons, thus delaying disease onset, accompanied by alleviation of muscle atrophy and improvements in motor function in SOD1[G93A] mice.}, } @article {pmid39084211, year = {2024}, author = {Sharma, S and Gilberto, VS and Rask, J and Chatterjee, A and Nagpal, P}, title = {Inflammasome-Inhibiting Nanoligomers Are Neuroprotective against Space-Induced Pathology in Healthy and Diseased Three-Dimensional Human Motor and Prefrontal Cortex Brain Organoids.}, journal = {ACS chemical neuroscience}, volume = {15}, number = {16}, pages = {3009-3021}, doi = {10.1021/acschemneuro.4c00160}, pmid = {39084211}, issn = {1948-7193}, mesh = {Humans ; *Prefrontal Cortex/drug effects/metabolism ; *Organoids/drug effects ; *Inflammasomes/metabolism ; Neuroprotective Agents/pharmacology ; Space Flight ; Weightlessness ; Neurodegenerative Diseases ; Alzheimer Disease/pathology/metabolism ; Amyotrophic Lateral Sclerosis/metabolism ; Frontotemporal Dementia/metabolism ; }, abstract = {The microgravity and space environment has been linked to deficits in neuromuscular and cognitive capabilities, hypothesized to occur due to accelerated aging and neurodegeneration in space. While the specific mechanisms are still being investigated, spaceflight-associated neuropathology is an important health risk to astronauts and space tourists and is being actively investigated for the development of appropriate countermeasures. However, such space-induced neuropathology offers an opportunity for accelerated screening of therapeutic targets and lead molecules for treating neurodegenerative diseases. Here, we show a proof-of-concept high-throughput target screening (on Earth), target validation, and mitigation of microgravity-induced neuropathology using our Nanoligomer platform, onboard the 43-day SpaceX CRS-29 mission to the International Space Station. First, comparing 3D healthy and diseased prefrontal cortex (PFC, for cognition) and motor neuron (MN, for neuromuscular function) organoids, we assessed space-induced pathology using biomarkers relevant to Alzheimer's disease (AD), frontotemporal dementia (FTD), and amyotrophic lateral sclerosis (ALS). Both healthy and diseased PFC and MN organoids showed significantly enhanced neurodegeneration in space, as measured through relevant disease biomarkers, when compared to their respective Earth controls. Second, we tested the top two lead molecules, NI112 that targeted NF-κB and NI113 that targeted IL-6. We observed that these Nanoligomers significantly mitigate the AD, FTD, and ALS relevant biomarkers like amyloid beta-42 (Aβ42), phosphorylated tau (pTau), Kallikrein (KLK-6), Tar DNA-binding protein 43 (TDP-43), and others. Moreover, the 43-day Nanoligomer treatment of these brain organoids did not appear to cause any observable toxicity or safety issues in the target organoid tissue, suggesting good tolerability for these molecules in the brain at physiologically relevant doses. Together, these results show significant potential for both the development and translation of NI112 and NI113 molecules as potential neuroprotective countermeasures for safer space travel and demonstrate the usefulness of the space environment for rapid, high-throughput screening of targets and lead molecules for clinical translation. We assert that the use of microgravity in drug development and screening may ultimately benefit millions of patients suffering from debilitating neurodegenerative diseases on Earth.}, } @article {pmid39083229, year = {2024}, author = {Kaji, R and Izumi, Y and Oki, R}, title = {Ultra-high dose methylcobalamin and other emerging therapies for amyotrophic lateral sclerosis.}, journal = {Current opinion in neurology}, volume = {37}, number = {5}, pages = {593-602}, doi = {10.1097/WCO.0000000000001311}, pmid = {39083229}, issn = {1473-6551}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy ; *Vitamin B 12/analogs & derivatives/therapeutic use/administration & dosage ; Clinical Trials as Topic ; }, abstract = {PURPOSE OF REVIEW: Recent development in understanding the pathophysiology of amyotrophic lateral sclerosis (ALS) has led to increasing number of promising test drugs in the pipeline along with the existing ones. We will review these agents focusing on ultra-high dose methylcobalamin, which is pending approval in Japan. Clinical trial design best suited for ALS will also be discussed.

RECENT FINDINGS: The most recent phase 3 trial (JETALS) of ultra-high dose methylcobalamin demonstrated significant slowing of ALSFRSR changes (0.5/month), with marked reduction of serum homocysteine levels in the initial double-blind period. The post hoc analysis of the previous phase 2/3 study (E761 trial; Eisai) showed that it prolonged survival of ALS patients, if started within 1 year of onset, but the previous studies suggested its efficacy even in later stages, depending upon the rate of progression. Phase 3 trial of AMX0035 or Relyvrio on the other hand showed negative results despite the promising phase 2 data. The latter did not adjust the disease progression rate before entry.

SUMMARY: Ultra-high dose methylcobalamin is not a vitamin supplement but a novel disease-modifying therapy for ALS, and it emphasizes homocysteine as a key factor in the disease process. Clinical trial design must include entering patients early and with similar rates of progression using pretrial observation periods for meaningful results, since ALS is a chronologically heterogenous condition with similar phenotypes.}, } @article {pmid39080220, year = {2025}, author = {Han, M and Raymond, J and Larson, TC and Mehta, P and Horton, DK}, title = {Correction to: Comparison of Demographics: National Amyotrophic Lateral Sclerosis Registry and Clinical Trials Data.}, journal = {Journal of racial and ethnic health disparities}, volume = {12}, number = {4}, pages = {2821}, doi = {10.1007/s40615-024-02110-0}, pmid = {39080220}, issn = {2196-8837}, } @article {pmid39079696, year = {2024}, author = {Tress, F and Luecke, E and Stegemann-Koniszewski, S and Lux, A and Singla, A and Schreiber, J}, title = {Prediction of nocturnal ventilation by pulmonary function testing in patients with amyotrophic lateral sclerosis.}, journal = {Pneumologie (Stuttgart, Germany)}, volume = {78}, number = {9}, pages = {626-633}, doi = {10.1055/a-2349-0936}, pmid = {39079696}, issn = {1438-8790}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology/therapy/diagnosis/complications ; Female ; Male ; Aged ; *Respiratory Function Tests ; Retrospective Studies ; Middle Aged ; Noninvasive Ventilation/methods ; Sensitivity and Specificity ; Reproducibility of Results ; Respiratory Insufficiency/therapy/physiopathology/etiology/diagnosis ; Polysomnography/methods ; Circadian Rhythm/physiology ; }, abstract = {BACKGROUND: In amyotrophic lateral sclerosis (ALS) prognosis is poor due to progressive weakening of the respiratory muscles. Survival and quality of life can be improved by noninvasive ventilation (NIV), which is initially applied while sleeping. The indication for NIV is based on pulmonary function testing (PFT) and polysomnography (PSG) with capnography (tCO2). While it is desirable to predict nocturnal ventilation by waking PFT in ALS, the parameters suited for reliable predictions remain elusive.

METHODS: We retrospectively analyzed parameters derived from PFT (spirometry, body plethysmography, diffusion capacity, respiratory muscle testing) and blood gas analysis, PSG and tCO2 in 42 patients with ALS (27 men, 15 women, age 69 ± 12.1 years) and performed Spearman's correlation analysis of daytime waking parameters and nighttime sleep parameters.

RESULTS: 28 patients (66.7%) showed restrictive impairment of ventilation and 15 patients (48.3%) showed insufficiency of the respiratory musculature. There was no obstructive impairment of ventilation. We did not observe any significant correlations between any single daytime PFT parameter with nocturnal pCO2. However, there were significant correlations between the ratios PIF/PEF, MEF50/MIF50, DLCO/VA as well as FEV1/FVC and nocturnal pCO2. Highly normal FEV1/FVC and Krogh-Factor (DLCOc/VA) indicated nocturnal hypercapnia. Furthermore, waking hypercapnia, concentrations of bicarbonate and base excess were each positively correlated with nocturnal hypercapnia.

CONCLUSIONS: Waking PFT is not a good predictor of nocturnal ventilation. Inspiratory parameters as well as the ratios FEV1/FVC and DLCO/VA performed best and should be included in the interpretation. Our analyses confirm the relevance of inspiratory muscle weakness in ALS. PSG and tCO2 remain the gold standard for the assessment of nocturnal ventilation.}, } @article {pmid39079071, year = {2024}, author = {Crayle, JI and Rampersaud, E and Myers, JR and Wuu, J and Taylor, JP and Wu, G and Benatar, M and Bedlack, RS}, title = {Genetic Associations With an Amyotrophic Lateral Sclerosis Reversal Phenotype.}, journal = {Neurology}, volume = {103}, number = {4}, pages = {e209696}, pmid = {39079071}, issn = {1526-632X}, mesh = {Aged ; Female ; Humans ; Male ; Middle Aged ; *Amyotrophic Lateral Sclerosis/genetics ; Cohort Studies ; *Genome-Wide Association Study ; *Phenotype ; Polymorphism, Single Nucleotide ; Quantitative Trait Loci ; Whole Genome Sequencing ; }, abstract = {BACKGROUND AND OBJECTIVES: The term "ALS Reversal" describes patients who initially meet diagnostic criteria for amyotrophic lateral sclerosis (ALS) or had clinical features most consistent with progressive muscular atrophy (PMA) but subsequently demonstrated substantial and sustained clinical improvement. The objective of this genome-wide association study (GWAS) was to identify correlates of this unusual clinical phenotype.

METHODS: Participants were recruited from a previously created database of individuals with the ALS Reversal phenotype. Whole-genome sequencing (WGS) data were compared with ethnicity-matched patients with typically progressive ALS enrolled through the CReATe Consortium's Phenotype-Genotype-Biomarker (PGB) study. These results were replicated using an independent ethnically matched WGS data set from Target ALS. Significant results were further explored with available databases of genetic regulatory markers and expression quantitative trait loci (eQTL) analysis.

RESULTS: WGS from 22 participants with documented ALS Reversals was compared with the PGB primary cohort (n = 103) and the Target ALS validation cohort (n = 140). Two genetic loci met predefined criteria for statistical significance (two-sided permutation p ≤ 0.01) and remained plausible after fine-mapping. The lead single nucleotide variant (SNV) from the first locus was rs4242007 (primary cohort GWAS OR = 12.0, 95% CI 4.1 to 34.6), which is in an IGFBP7 intron and is in near-perfect linkage disequilibrium with a SNV in the IGFBP7 promoter region. Both SNVs are associated with decreased frontal cortex IGFBP7 expression in eQTL data sets. Notably, 3 Reversals, but none of the typically progressive individuals (n = 243), were homozygous for rs4242007. The importance of the second locus, located near GRIP1, is uncertain given the absence of an associated effect on nearby gene transcription.

DISCUSSION: We found a significant association between the Reversal phenotype and an IGFBP7 noncoding SNV that is associated with IGFBP7 expression. This is biologically relevant as IGFBP7 is a reported inhibitor of the insulin growth factor-1 (IGF-1) receptor that activates the possibly neuroprotective IGF-1 signaling pathway. This finding is limited by small sample size but suggests that there may be merit in further exploration of IGF-1 pathway signaling as a therapeutic mechanism for ALS.

This study was registered with ClinicalTrials.gov (NCT03464903) on March 14, 2018. The first participant was enrolled on June 22, 2018.}, } @article {pmid39079069, year = {2024}, author = {Fournier, CN}, title = {Learning From the Exception and Not the Rule: Genetic Associations With an Amyotrophic Lateral Sclerosis Reversal Phenotype.}, journal = {Neurology}, volume = {103}, number = {4}, pages = {e209780}, doi = {10.1212/WNL.0000000000209780}, pmid = {39079069}, issn = {1526-632X}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics ; *Phenotype ; }, } @article {pmid39076845, year = {2024}, author = {Liu, X and Chen, L and Ye, S and Liu, X and Zhang, Y and Fan, D}, title = {Postural instability and lower extremity dysfunction in upper motor neuron-dominant amyotrophic lateral sclerosis.}, journal = {Frontiers in neurology}, volume = {15}, number = {}, pages = {1406109}, pmid = {39076845}, issn = {1664-2295}, abstract = {BACKGROUND: Upper motor neuron-dominant ALS (UMND ALS) is recognized to have early onset and good prognosis, but may have a rapid decline in motor function due to gait instability in the early stage. We investigated changes in lower extremity function in UMND ALS, particularly UMND ALS patients accompanied with postural instability or repeated falls (UMND ALS plus).

RESULTS: Among the 2,353 ALS patients reviewed, 211 (9.0%) had UMND ALS. UMND ALS had a longer diagnosis delay and restricted symptoms. Although UMND ALS patients had better lower extremity function and strength than matched classic ALS patients on first evaluation, there was no difference in the time of needing assistance or not being able to walk after disease onset. In contrast, UMND ALS plus has severe UMN symptoms and a more rapid decline in motor function. The lower extremity function was no better than that in the matched classic ALS. The prognosis of UMND ALS and UMND ALS plus were significantly better than those of overall ALS.

CONCLUSION: UMND ALS has restricted symptoms but has a rapid decline in lower extremity function in the early stage of the disease. The motor function decline of UMND ALS plus is as fast as classic ALS. Whether these patients represent a distinct subgroup of ALS deserves further investigation.}, } @article {pmid39076207, year = {2024}, author = {Zheng, W and He, J and Chen, L and Yu, W and Zhang, N and Liu, X and Fan, D}, title = {Genetic link between KIF1A mutations and amyotrophic lateral sclerosis: evidence from whole-exome sequencing.}, journal = {Frontiers in aging neuroscience}, volume = {16}, number = {}, pages = {1421841}, pmid = {39076207}, issn = {1663-4365}, abstract = {OBJECTIVES: Genetics have been shown to have a substantial impact on amyotrophic lateral sclerosis (ALS). The ALS process involves defects in axonal transport and cytoskeletal dynamics. It has been identified that KIF1A, responsible for encoding a kinesin-3 motor protein that carries synaptic vesicles, is considered a genetic predisposing factor for ALS.

METHODS: The analysis of whole-exome sequencing data from 1,068 patients was conducted to examine the genetic link between ALS and KIF1A. For patients with KIF1A gene mutations and a family history, we extended the analysis to their families and reanalyzed them using Sanger sequencing for cosegregation analysis.

RESULTS: In our cohort, the KIF1A mutation frequency was 1.31% (14/1,068). Thirteen nonsynonymous variants were detected in 14 ALS patients. Consistent with the connection between KIF1A and ALS, the missense mutation p.A1083T (c.3247G>A) was shown to cosegregate with disease. The mutations related to ALS in our study were primarily located in the cargo-binding region at the C-terminal, as opposed to the mutations of motor domain at the N-terminal of KIF1A which were linked to hereditary peripheral neuropathy and spastic paraplegia. We observed high clinical heterogeneity in ALS patients with missense mutations in the KIF1A gene. KIF5A is a more frequent determinant of ALS in the European population, while KIF1A accounts for a similar proportion of ALS in both the European and Chinese populations.

CONCLUSION: Our investigation revealed that mutations in the C-terminus of KIF1A could increase the risk of ALS, support the pathogenic role of KIF1A in ALS and expand the phenotypic and genetic spectrum of KIF1A-related ALS.}, } @article {pmid39075916, year = {2025}, author = {Wu, J and Ye, S and Liu, X and Xu, Y and Fan, D}, title = {The burden of upper motor neuron involvement is correlated with the bilateral limb involvement interval in patients with amyotrophic lateral sclerosis: a retrospective observational study.}, journal = {Neural regeneration research}, volume = {20}, number = {5}, pages = {1505-1512}, pmid = {39075916}, issn = {1673-5374}, abstract = {JOURNAL/nrgr/04.03/01300535-202505000-00032/figure1/v/2024-07-28T173839Z/r/image-tiff Amyotrophic lateral sclerosis is a rare neurodegenerative disease characterized by the involvement of both upper and lower motor neurons. Early bilateral limb involvement significantly affects patients' daily lives and may lead them to be confined to bed. However, the effect of upper and lower motor neuron impairment and other risk factors on bilateral limb involvement is unclear. To address this issue, we retrospectively collected data from 586 amyotrophic lateral sclerosis patients with limb onset diagnosed at Peking University Third Hospital between January 2020 and May 2022. A univariate analysis revealed no significant differences in the time intervals of spread in different directions between individuals with upper motor neuron-dominant amyotrophic lateral sclerosis and those with classic amyotrophic lateral sclerosis. We used causal directed acyclic graphs for risk factor determination and Cox proportional hazards models to investigate the association between the duration of bilateral limb involvement and clinical baseline characteristics in amyotrophic lateral sclerosis patients. Multiple factor analyses revealed that higher upper motor neuron scores (hazard ratio [HR] = 1.05, 95% confidence interval [CI] = 1.01-1.09, P = 0.018), onset in the left limb (HR = 0.72, 95% CI = 0.58-0.89, P = 0.002), and a horizontal pattern of progression (HR = 0.46, 95% CI = 0.37-0.58, P < 0.001) were risk factors for a shorter interval until bilateral limb involvement. The results demonstrated that a greater degree of upper motor neuron involvement might cause contralateral limb involvement to progress more quickly in limb-onset amyotrophic lateral sclerosis patients. These findings may improve the management of amyotrophic lateral sclerosis patients with limb onset and the prediction of patient prognosis.}, } @article {pmid39075908, year = {2025}, author = {Araúzo-Bravo, MJ and Gerovska, D and Schwab, M and Kretz, A}, title = {Small extrachromosomal circular DNA in amyotrophic lateral sclerosis matter.}, journal = {Neural regeneration research}, volume = {20}, number = {5}, pages = {1411-1413}, pmid = {39075908}, issn = {1673-5374}, } @article {pmid39075842, year = {2025}, author = {Lomnicka, I and Dubey, S and Waller, P and Vora, D and Dirikolu, L}, title = {Development and validation of general plasma screening method for performance enhancing drugs in racehorses utilizing liquid chromatography-high-resolution mass spectrometry (LC-HRMS).}, journal = {Drug testing and analysis}, volume = {17}, number = {6}, pages = {735-750}, doi = {10.1002/dta.3774}, pmid = {39075842}, issn = {1942-7611}, support = {//Louisiana State Racing Commission, New Orleans, LA 70119/ ; }, mesh = {Horses/blood ; Animals ; *Doping in Sports ; *Substance Abuse Detection/methods/veterinary ; Solid Phase Extraction/methods ; Chromatography, High Pressure Liquid/methods ; *Performance-Enhancing Substances/blood ; *Mass Spectrometry/methods ; Limit of Detection ; Chromatography, Liquid/methods ; High-Throughput Screening Assays/methods ; Tandem Mass Spectrometry/methods ; }, abstract = {The screening of drugs in plasma and urine often requires initial extraction (such as liquid-liquid extraction and solid-phase extraction) before the samples are submitted to instrumental analyses. These extraction procedures are often laborious and time-consuming. In this manuscript, a high-throughput automated assay based on liquid chromatography-high-resolution mass spectrometry (LC-HRMS) suitable for use as an initial testing procedure covering multiple classes of compounds prohibited in horse racing is described. The assay requires a 600-μL plasma aliquot, which is subjected to solid phase extraction (SPE) using OASIS HLB 96-well SPE with Biotage Extrahera system, evaporation, and reconstitution in a 96-well collection plate. LC-HRMS analyses were carried out on a Thermo Q-Exactive Mass spectrometer coupled with Thermo UHPLC system equipped with Thermo Accela ALS 2.4.0 autosampler linked to ACE Excel column. Drug targets were detected by retention time and accurate mass, with a mass tolerance window of 5 ppm in positive and negative ionization mode. The screening method was validated for over 300 drug targets in a 13-min run. Validation data including sensitivity, specificity, extraction recovery, and precision are presented. As the method employs full-scan mass spectrometry, unlimited number of drug targets can theoretically be incorporated into this method.}, } @article {pmid39075493, year = {2024}, author = {Mangal, AL and Mücke, M and Rolke, R and Appelmann, I}, title = {Advance directives in amyotrophic lateral sclerosis - a systematic review and meta-analysis.}, journal = {BMC palliative care}, volume = {23}, number = {1}, pages = {191}, pmid = {39075493}, issn = {1472-684X}, mesh = {*Amyotrophic Lateral Sclerosis/psychology/therapy/complications ; Humans ; *Advance Directives/statistics & numerical data/psychology ; Advance Care Planning/statistics & numerical data/standards ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease of the upper and lower motoneuron. It is associated with a life expectancy of 2-4 years after diagnosis. Individuals experience paralysis, dysphagia, respiratory failure and loss of communicative function, rendering advance care planning (ACP) critically important. This systematic review primarily aimed to internationally compare the application of advance directives (AD) and ACP in ALS. Its secondary aim was to identify ACP preferences, identify fields for future research and to generate recommendations for improving patient care through ACP.

METHODS: We conducted a systematic literature review and meta-analysis. Five electronic databases (Embase, Medline, Scopus, PsycInfo and CENTRAL) were searched for qualitative and quantitative primary literature from 1999 to 2024. Cross-references were used to identify additional publications. Study selection was performed based on inclusion criteria. Number and content of AD were extracted systematically. After statistical analysis consecutive meta-analysis was performed for international differences and changes over time. Quality assessment of studies was performed using the MMAT (Mixed Methods Appraisal Tool). PROSPERO Registration (June 07, 2021) : CRD42021248040.

RESULTS: A total of 998 records was screened of which 26 were included in the synthesis. An increase in publication numbers of 88.9% was observed from 1999 to 2024. Results regarding use and content of AD were heterogeneous and international differences were detected. AD were signed in 60.4% of records (1,629 / 2,696 patients). The number of AD decreased over time when separating the review period in two decades (1st 1999-2011: 78% vs. 2nd 2012-2024: 42%). Study quality was superior in qualitative and mixed method designs compared to quantitative studies.

CONCLUSION: Further prospective studies should include detailed analyses on preferences regarding ventilation and artificial nutrition in ALS and should encompass countries of the global south. Despite the complexity of ACP with regard to individual patient needs, ACP should be part of each individual support plan for ALS patients and should specifically comprise a discussion on the preferred place of death. The available disease-specific AD documents should be preferred.}, } @article {pmid39073874, year = {2024}, author = {Gatch, AJ and Ding, F}, title = {TDP-43 Promotes Amyloid-Beta Toxicity by Delaying Fibril Maturation via Direct Molecular Interaction.}, journal = {ACS chemical neuroscience}, volume = {15}, number = {15}, pages = {2936-2953}, pmid = {39073874}, issn = {1948-7193}, support = {P20 GM121342/GM/NIGMS NIH HHS/United States ; R35 GM145409/GM/NIGMS NIH HHS/United States ; }, mesh = {*Amyloid beta-Peptides/metabolism ; *DNA-Binding Proteins/metabolism ; Humans ; *Molecular Dynamics Simulation ; *Amyloid/metabolism ; Protein Binding ; Alzheimer Disease/metabolism ; }, abstract = {Amyloid-β (Aβ) is a peptide that undergoes self-assembly into amyloid fibrils, which compose the hallmark plaques observed in Alzheimer's disease (AD). TAR DNA-binding protein 43 (TDP-43) is a protein with mislocalization and aggregation implicated in amyotrophic lateral sclerosis and other neurodegenerative diseases. Recent work suggests that TDP-43 may interact with Aβ, inhibiting the formation of amyloid fibrils and worsening AD pathology, but the molecular details of their interaction remain unknown. Using all-atom discrete molecular dynamics simulations, we systematically investigated the direct molecular interaction between Aβ and TDP-43. We found that Aβ monomers were able to bind near the flexible nuclear localization sequence of the N-terminal domain (NTD) of TDP-43, adopting β-sheet rich conformations that were promoted by the interaction. Furthermore, Aβ associated with the nucleic acid binding interface of the tandem RNA recognition motifs of TDP-43 via electrostatic interactions. Using the computational peptide array method, we found the strongest C-terminal domain interaction with Aβ to be within the amyloidogenic core region of TDP-43. With experimental evidence suggesting that the NTD is necessary for inhibiting Aβ fibril growth, we also simulated the NTD with an Aβ40 fibril seed. We found that the NTD was able to strongly bind the elongation surface of the fibril seed via extensive hydrogen bonding and could also diffuse along the lateral surface via electrostatic interactions. Our results suggest that TDP-43 binding to the elongation surface, thereby sterically blocking Aβ monomer addition, is responsible for the experimentally observed inhibition of fibril growth. We conclude that TDP-43 may promote Aβ toxicity by stabilizing the oligomeric state and kinetically delaying fibril maturation.}, } @article {pmid39073543, year = {2024}, author = {Litvinov, VV and Freynd, GG}, title = {[Clinical and morphologic characterization of Pick's dementia: case report and review of the literature].}, journal = {Arkhiv patologii}, volume = {86}, number = {4}, pages = {51-57}, doi = {10.17116/patol20248604151}, pmid = {39073543}, issn = {0004-1955}, mesh = {Humans ; *Cerebral Cortex/metabolism/pathology ; *Pick Disease of the Brain/pathology/diagnosis ; tau Proteins/metabolism ; }, abstract = {Diseases morphologically characterized by frontotemporal lobar degeneration have relatively recently been considered as a group of frontotemporal dementias. This group is characterized by a tendency to early clinical onset of dementia, common genetic and morphological features, as well as a possible association with diseases such as amyotrophic lateral sclerosis and atypical parkinsonism syndrome. Historically, Pick's dementia (Pick's disease) was described as the first of the frontotemporal dementias, which is morphologically characterized by the presence of argyrophilic Pick's bodies represented by 3R-tau protein in the neurons of the cerebral cortex. Despite the characteristic clinical and morphological picture due to the relative rarity, the diagnosis of Pick's dementia is infrequently made by both clinicians and pathologists. The article presents current data on frontotemporal dementia. A case of Pick's dementia with characteristic clinical manifestations in the form of early onset of behavioral and personality disorders, as well as specific morphological changes in the brain, is described.}, } @article {pmid39073531, year = {2024}, author = {Moglia, C and Palumbo, F and Botto, R and Iazzolino, B and Ticozzi, N and Calvo, A and Leombruni, P and , }, title = {Prognostic communication in amyotrophic lateral sclerosis: findings from a Nationwide Italian survey.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {45}, number = {12}, pages = {5787-5794}, pmid = {39073531}, issn = {1590-3478}, support = {RF-2016-02362405//Ministero della Salute/ ; 23C306//Ministero della Salute/ ; 101017598//Ministero dell'Istruzione, dell'Università e della Ricerca/ ; 2017SNW5MB//Ministero dell'Istruzione, dell'Università e della Ricerca/ ; 259867//Seventh Framework Programme/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/therapy/diagnosis ; Humans ; Italy ; Prognosis ; *Neurologists ; *Attitude of Health Personnel ; Communication ; Surveys and Questionnaires ; Male ; Female ; }, abstract = {BACKGROUND: Amyotrophic Lateral Sclerosis (ALS) is a fatal motor neuron disease with a highly variable prognosis. Among the proposed prognostic models, the European Network for the cure of ALS (ENCALS) survival model has demonstrated good predictive performance. However, few studies have examined prognostic communication and the diffusion of prognostic algorithms in ALS care.

OBJECTIVE: To investigate neurologists' attitudes toward prognostic communication and their knowledge and utilization of the ENCALS survival model in clinical practice.

METHODS: A web-based survey was administered between May 2021 and March 2022 to the 40 Italian ALS Centers members of the Motor Neuron Disease Study Group of the Italian Society of Neurology.

RESULTS: Twenty-two out of 40 (55.0%) Italian ALS Centers responded to the survey, totaling 37 responses. The model was known by 27 (73.0%) respondents. However, it was predominantly utilized for research (81.1%) rather than for clinical prognostic communication (7.4%). Major obstacles to prognostic communication included the unpredictability of disease course, fear of a negative impact on patients or caregivers, dysfunctional reaction to diagnosis, and cognitive impairment. Nonetheless, the model was viewed as potentially useful for improving clinical management, increasing disease awareness, and facilitating care planning, especially end-of-life planning.

CONCLUSIONS: Despite the widespread recognition and positive perceptions of the ENCALS survival model among Italian neurologists with expertise in ALS, its implementation in clinical practice remains limited. Addressing this disparity may require systematic investigations and targeted training to integrate tailored prognostic communication into ALS care protocols, aligning with the growing availability of prognostic tools for ALS.}, } @article {pmid39073225, year = {2024}, author = {Liu, X and Xue, H and Wirdefeldt, K and Song, H and Smedby, K and Fang, F and Liu, Q}, title = {Clonal hematopoiesis of indeterminate potential and risk of neurodegenerative diseases.}, journal = {Journal of internal medicine}, volume = {296}, number = {4}, pages = {327-335}, doi = {10.1111/joim.20001}, pmid = {39073225}, issn = {1365-2796}, support = {//Initial Founding for High Level Talented Scholars in Nanfang Hospital/ ; 2023G001//Southern Medical University/ ; 2021-00696//Swedish Research Council (JPND)/ ; P1030//Initial Founding for Postdoc in Greater Bay Area Institute of Precision Medicine (Guangzhou)/ ; }, mesh = {Humans ; *Neurodegenerative Diseases/genetics/epidemiology ; Female ; Male ; *Clonal Hematopoiesis/genetics ; Middle Aged ; Aged ; Risk Factors ; DNA Methyltransferase 3A ; United Kingdom/epidemiology ; Cohort Studies ; DNA (Cytosine-5-)-Methyltransferases/genetics ; Repressor Proteins/genetics ; Amyotrophic Lateral Sclerosis/genetics ; Parkinson Disease/genetics ; DNA-Binding Proteins ; Dioxygenases ; }, abstract = {BACKGROUND: Little is known regarding the association between clonal hematopoiesis of indeterminate potential (CHIP) and risk of neurodegenerative diseases.

OBJECTIVE: To estimate the risk of neurodegenerative diseases among individuals with CHIP.

METHODS: We conducted a community-based cohort study based on UK Biobank and used Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the risk of any neurodegenerative disease, subtypes of neurodegenerative diseases (including primary neurodegenerative diseases, vascular neurodegenerative diseases, and other neurodegenerative diseases), and specific diagnoses of neurodegenerative diseases (i.e., amyotrophic lateral sclerosis [ALS], Alzheimer's disease [AD], and Parkinson's disease [PD]) associated with CHIP.

RESULTS: We identified 14,440 individuals with CHIP and 450,907 individuals without CHIP. Individuals with CHIP had an increased risk of any neurodegenerative disease (HR 1.10, 95% CI: 1.01-1.19). We also observed a statistically significantly increased risk for vascular neurodegenerative diseases (HR 1.31, 95% CI 1.05-1.63) and ALS (HR 1.50, 95% CI 1.05-2.15). An increased risk was also noted for other neurodegenerative diseases (HR 1.13, 95% CI 0.97-1.32), although not statistically significant. Null association was noted for primary neurodegenerative diseases (HR 1.06, 95% CI 0.96-1.17), AD (HR 1.04, 95% CI 0.88-1.23), and PD (HR 1.02, 95% CI 0.86-1.21). The risk increase in any neurodegenerative disease was mainly observed for DNMT3A-mutant CHIP, ASXL1-mutant CHIP, or SRSF2-mutant CHIP.

CONCLUSION: Individuals with CHIP were at an increased risk of neurodegenerative diseases, primarily vascular neurodegenerative diseases and ALS, but potentially also other neurodegenerative diseases. These findings suggest potential shared mechanisms between CHIP and neurodegenerative diseases.}, } @article {pmid39073146, year = {2024}, author = {Bublitz, SK and Eham, M and Ellrott, H and Littger, B and Richter, J and Lorenzl, S}, title = {Homecare amyotrophic lateral sclerosis (ALS): A multidisciplinary, home-based model of care for patients with ALS and their caregivers.}, journal = {Muscle & nerve}, volume = {70}, number = {5}, pages = {937-943}, doi = {10.1002/mus.28218}, pmid = {39073146}, issn = {1097-4598}, support = {//Bavarian Ministry of Health/ ; //Krankenhaus Agatharied/ ; //Dr. Mähler-Linke Stiftung/ ; //ALS Hilfe Bayern e.V./ ; //Marion von Tessin-Stiftung/ ; //Archdiocese München and Freising/ ; //Amylyx Pharmaceuticals Germany GmbH/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy/psychology ; Male ; Female ; *Caregivers/psychology ; Middle Aged ; Aged ; *Home Care Services ; Pilot Projects ; Longitudinal Studies ; Patient Satisfaction ; Patient Care Team ; Adult ; Palliative Care ; Cohort Studies ; Germany ; Terminal Care ; Aged, 80 and over ; }, abstract = {INTRODUCTION/AIMS: Multidisciplinary care for patients with amyotrophic lateral sclerosis (ALS) is recommended in international guidelines, but reaches its limits when immobility increases. This pilot project addresses this gap by delivering home-based, specialized, multiprofessional support to ALS patients who are not able to attend outpatient care. The study assessed the feasibility of this model of care and the satisfaction of both patients and caregivers.

METHODS: This was a longitudinal cohort study of patients with ALS and their caregivers in the surroundings of Munich, Germany. Patients were regularly visited at home by a multiprofessional team (neurologists/palliative care physicians, nurse, social worker, chaplain).

RESULTS: A total of 94 patients with ALS were included in the homecare project and 88 patients and 74 caregivers were enrolled in the accompanying study. The mean care duration was 221 days, enabling 61% of the 49 deceased patients to die at home. Notably, 20% of patients chose a way to hasten death. Patient satisfaction (ICECAP Supportive Care Measure [SCM]: 23.7/28, CollaboRATE: 10.6/12) and caregiver perception of the end-of-life phase (Caregiver Evaluation of the Quality of End-Of-Life Care [CEQUEL]: 24.9/26) were high.

DISCUSSION: This pilot project successfully implemented specialized, home-based multidisciplinary care for ALS patients and caregivers, demonstrating both feasibility and high satisfaction. The program enabled a large proportion of patients to remain in their homes, reducing the need for hospital care. The multiprofessional approach, including neuropalliative, psychosocial and spiritual support provided comprehensive care that addressed needs of patients and caregivers. Further research is warranted to explore cost-effectiveness.}, } @article {pmid39072769, year = {2024}, author = {Turner, J and Bruels, CC and Daugherty, AL and Estrella, EA and Stafki, S and Syeda, SB and Littel, HR and Pais, L and Ganesh, VS and Lidov, HGW and Paine, SML and Maddison, P and Harrison, RE and Straub, V and Ghosh, PS and Pacak, CA and Kunkel, LM and Draper, I and Topf, A and Kang, PB}, title = {Dominant stop-loss HNRNPA1 variants in juvenile-onset myopathy.}, journal = {Muscle & nerve}, volume = {70}, number = {4}, pages = {843-850}, pmid = {39072769}, issn = {1097-4598}, support = {//Muscular Dystrophy UK/ ; //Ultragenyx/ ; R01 HG009141/HG/NHGRI NIH HHS/United States ; //Coalition to Cure Calpain 3/ ; //LGMD2I Research Fund/ ; R01HG009141/HG/NHGRI NIH HHS/United States ; //Kurt+Peter Foundation/ ; UM1HG008900//National Heart, Lung and Blood Institute/ ; //Sanofi Genzyme/ ; UM1 HG008900/HG/NHGRI NIH HHS/United States ; P50 HD105351/HD/NICHD NIH HHS/United States ; //Bernard F. and Alva B. Gimbel Foundation/ ; //LGMD2D Foundation/ ; //Samantha J. Brazzo Foundation/ ; /EY/NEI NIH HHS/United States ; }, mesh = {Humans ; Male ; *Heterogeneous Nuclear Ribonucleoprotein A1/genetics ; Female ; Adolescent ; Muscular Diseases/genetics ; Muscle, Skeletal/pathology ; Young Adult ; Phenotype ; }, abstract = {INTRODUCTION/AIMS: Heterogeneous nuclear ribonucleoprotein A1 is involved in nucleic acid homeostatic functions. The encoding gene HNRNPA1 has been associated with several neuromuscular disorders including an amyotrophic lateral sclerosis-like phenotype, distal hereditary motor neuropathy, multisystem proteinopathy, and various myopathies. We report two unrelated individuals with monoallelic stop loss variants affecting the same codon of HNRNPA1.

METHODS: Two individuals with unsolved juvenile-onset myopathy were enrolled under approved institutional protocols. Phenotype data were collected and genetic analyses were performed, including whole-exome sequencing (WES).

RESULTS: The two probands (MNOT002-01 and K1440-01) showed a similar onset of slowly progressive extremity and facial weakness in early adolescence. K1440-01 presented with facial weakness, winged scapula, elevated serum creatine kinase (CK) levels, and mild neck weakness. MNOT002-01 also exhibited elevated CK levels along with facial weakness, cardiomyopathy, respiratory dysfunction, pectus excavatum, a mildly rigid spine, and loss of ambulation. On quadriceps muscle biopsy, K1440-01 displayed rounded myofibers, mild variation in fiber diameter, and type 2 fiber hypertrophy, while MNOT002-01 displayed rimmed vacuoles. Monoallelic stop-loss variants in HNRNPA1 were identified for both probands: c.1119A>C p.*373Tyrext*6 (K1440-01) and c.1118A>C p.*373Serext*6 (MNOT002-01) affect the same codon and are both predicted to lead to the addition of six amino acids before termination at an alternative stop codon.

DISCUSSION: Both stop-loss variants in our probands are likely pathogenic. Our findings contribute to the disease characterization of pathogenic variants in HNRNPA1. This gene should be screened in clinical diagnostic testing of unsolved cases of sporadic or dominant juvenile-onset myopathy.}, } @article {pmid39072749, year = {2025}, author = {Stevenor, BA and Burgess, Y and Sampson, G and McBride, NL and Gugiu, MR and Copella, J and Davis, J and Wu, B and Panchal, AR}, title = {Examining the Reliability and Validity of the ALS Certification Examinations with the Inclusion of Clinical Judgment: An Update on the ALS Examination Redesign.}, journal = {Prehospital emergency care}, volume = {29}, number = {3}, pages = {289-295}, doi = {10.1080/10903127.2024.2379879}, pmid = {39072749}, issn = {1545-0066}, mesh = {Humans ; Reproducibility of Results ; *Certification/standards ; *Emergency Medical Technicians/standards/education ; Psychometrics ; *Clinical Competence/standards ; *Educational Measurement/methods/standards ; *Emergency Medical Services/standards ; *Advanced Cardiac Life Support/standards ; Male ; Female ; }, abstract = {OBJECTIVES: Clinical judgment describes the process an emergency medical service clinician uses to evaluate problems and make decisions in the out-of-hospital setting. As part of the redesign of the Advanced Life Support (ALS) certification examinations, the National Registry of Emergency Medical Technicians is developing and evaluating items that measure clinical judgment, with the intention of assessing these as a new domain in the ALS certification examinations. In this study, we provide evidence around the redesign by evaluating the reliability and validity of the advanced emergency medical technician (AEMT) and paramedic certification examinations when clinical judgment is included as a sixth domain along with the five current domains.

METHODS: Pretest (i.e., pilot, unscored) clinical judgment items were included as a new sixth clinical judgment domain. We then used the combination of operational (i.e., scored) and pretest items for all six domains and scored the redesigned AEMT and paramedic certification examinations. We evaluated the psychometric properties of these ALS examinations within the Rasch measurement framework with multiple assessments of reliability and validity including item-level statistics (e.g., mean-square infit and outfit, local dependence) and examination-level statistics (e.g., person reliability, item reliability, item separation, decision consistency, decision accuracy). Wright Maps were produced to evaluate whether the examination item difficulty statistics aligned with the candidate ability continuum.

RESULTS: The total population of all examination forms included were 20,136 (AEMT 4,983; paramedic 15,153). The Rasch-based statistics for the redesigned AEMT and paramedic examinations, for both item and examination-level statistics, were well within the psychometric standard values. Wright maps demonstrated that the developed items fall along the candidate ability continuum for both examinations. Further, the distribution of clinical judgment item difficulties fell within the current item distribution, providing evidence that these new items are of similar difficulty to the items measuring the five current domains.

CONCLUSION: We demonstrate strong reliability and validity evidence to support that the integrity of the examinations is upheld with the addition of clinical judgment items, while also providing a more robust candidate evaluation. Most importantly, the pass/fail decisions that candidates receive accurately reflect their level of ALS knowledge at the entry-level.}, } @article {pmid39072727, year = {2024}, author = {Defilippi, V and Petereit, J and Handlos, VJL and Notterpek, L}, title = {Quantitative proteomics unveils known and previously unrecognized alterations in neuropathic nerves.}, journal = {Journal of neurochemistry}, volume = {168}, number = {9}, pages = {3154-3170}, pmid = {39072727}, issn = {1471-4159}, support = {P20 GM130459/GM/NIGMS NIH HHS/United States ; GM104944/NH/NIH HHS/United States ; P20 GM103440/GM/NIGMS NIH HHS/United States ; P20GM130459/NH/NIH HHS/United States ; GM103440/NH/NIH HHS/United States ; U54 GM104944/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; *Proteomics/methods ; Mice ; Charcot-Marie-Tooth Disease/genetics/metabolism/pathology ; Myelin Proteins/genetics/metabolism ; Peripheral Nerves/metabolism/pathology ; Mice, Inbred C57BL ; Male ; Peripheral Nervous System Diseases/genetics/metabolism/pathology ; Female ; }, abstract = {Charcot-Marie-Tooth disease type 1E (CMT1E) is an inherited autosomal dominant peripheral neuropathy caused by mutations in the peripheral myelin protein 22 (PMP22) gene. The identical leucine-to-proline (L16P) amino acid substitution in PMP22 is carried by the Trembler J (TrJ) mouse and is found in CMT1E patients presenting with early-onset disease. Peripheral nerves of patients diagnosed with CMT1E display a complex and varied histopathology, including Schwann cell hyperproliferation, abnormally thin myelin, axonal degeneration, and subaxonal morphological changes. Here, we have taken an unbiased data-independent analysis (DIA) mass spectrometry (MS) approach to quantify proteins from nerves of 3-week-old, age and genetic strain-matched wild-type (Wt) and heterozygous TrJ mice. Nerve proteins were dissolved in lysis buffer and digested into peptide fragments, and protein groups were quantified by liquid chromatography-mass spectrometry (LC-MS). A linear model determined statistically significant differences between the study groups, and proteins with an adjusted p-value of less than 0.05 were deemed significant. This untargeted proteomics approach identified 3759 quality-controlled protein groups, of which 884 demonstrated differential expression between the two genotypes. Gene ontology (GO) terms related to myelin and myelin maintenance confirm published data while revealing a previously undetected prominent decrease in peripheral myelin protein 2. The dataset corroborates the described pathophysiology of TrJ nerves, including elevated activity in the proteasome-lysosomal pathways, alterations in protein trafficking, and an increase in three macrophage-associated proteins. Previously unrecognized perturbations in RNA processing pathways and GO terms were also discovered. Proteomic abnormalities that overlap with other human neurological disorders besides CMT include Lafora Disease and Amyotrophic Lateral Sclerosis. Overall, this study confirms and extends current knowledge on the cellular pathophysiology in TrJ neuropathic nerves and provides novel insights for future examinations. Recognition of shared pathomechanisms across discrete neurological disorders offers opportunities for innovative disease-modifying therapeutics that could be effective for distinct neuropathies.}, } @article {pmid39072497, year = {2025}, author = {Alonso, JP and Ini, N and Villarejo, A and Belizán, M and Roberti, J}, title = {Amyotrophic lateral sclerosis in Argentina: unveiling the burden of treatment through patient and caregiver perspectives.}, journal = {Disability and rehabilitation}, volume = {47}, number = {7}, pages = {1828-1835}, doi = {10.1080/09638288.2024.2385732}, pmid = {39072497}, issn = {1464-5165}, mesh = {Humans ; Argentina ; *Amyotrophic Lateral Sclerosis/psychology/therapy/rehabilitation/diagnosis/economics ; *Caregivers/psychology ; Female ; Male ; Middle Aged ; *Cost of Illness ; Qualitative Research ; Aged ; Interviews as Topic ; Adult ; Activities of Daily Living ; }, abstract = {PURPOSE: To examine the burden of treatment (BoT) experienced by people with Amyotrophic Lateral Sclerosis (ALS) in Argentina.

METHODS: Qualitative methodological design based on semi-structured interviews. Nineteen semi-structured interviews were conducted (PwALS = 7, informal caregivers= 12). The interview guides were designed based on the literature and BoT theory. Data were analysed following a framework analysis approach.

RESULTS: The research highlighted the arduous journey toward obtaining a diagnosis, marked by delays influenced by healthcare system inefficiencies, lack of disease awareness and pandemic-related anxiety. Receiving the diagnosis was a destabilising experience, triggering the need to reframe self-identity, a new reality. As the disease progressed, patients encountered significant challenges in their daily activities and basic tasks, affecting their ability to work, communicate, and manage personal care. The burden extended beyond the patients to their primary caregivers. Access to specialised care, bureaucratic complexities in securing treatment, and the financial impact of managing the disease posed substantial challenges.

CONCLUSION: The findings offer valuable insights into the experiences of PwALS and their caregivers in Argentina. They underscore the need for increased disease awareness, improved access to specialised care, and enhanced support networks to alleviate the burdens PwALS and their families face.}, } @article {pmid39071530, year = {2024}, author = {Gaspar, AD and Banayat, AC}, title = {Undergraduate Student Nurses' Satisfaction, Self-confidence, and Perception of High-fidelity Simulation-based Learning on Critically-ill Patients.}, journal = {Acta medica Philippina}, volume = {58}, number = {12}, pages = {110-117}, pmid = {39071530}, issn = {2094-9278}, abstract = {BACKGROUND AND OBJECTIVE: Replicating critical care practice settings in high-fidelity simulation (HFS) provides more learning opportunities to develop competencies, improve self-confidence, and learner satisfaction in a safe environment. Simulation is increasingly adopted globally as an alternative teaching strategy. Yet, data on the HFS experience of Filipino undergraduate nursing students is limited. This study describes the satisfaction, self-confidence, and perception of undergraduate nursing students on the use of HFS-based learning on critically-ill adult and pediatric patients requiring advanced life support (ALS).

METHODS: A quantitative, descriptive, correlational study was conducted using purposive sampling on all fourth-year BS Nursing students enrolled in Critical Care Nursing course in a state university. Data were collected through an online survey on demographic data, and the students' perceptions towards high-fidelity simulation-based learning (SBL) using three tools, namely: Simulation Design Scale, Educational Practices Questionnaire, and Student Satisfaction and Self-confidence in Learning. T-test and ANOVA were used to compare the means of the variables. Bivariate analysis (Pearson's product-moment correlation) was performed to find the relationship between variables.

RESULTS: A total of 86 students participated in the survey. Overall, the students were highly satisfied with the simulation experience (4.46 out of 5.0, SD=0.47), and had high ratings of self-confidence in SBL (4.44 out of 5.0, SD=0.42). Overall satisfaction level was positively related to student's perception on simulation design (r=0.61, p<0.01) and educational practices (r=0.59, p<0.01). Similarly, the students' overall self-confidence with SBL was also positively correlated with their perceptions of the simulation design (r=0.32, p<0.01), and educational practices (r=0.34, p<0.01).

CONCLUSION: Effective use of technology through HFS-based learning is useful in increasing satisfaction and self-confidence of Filipino undergraduate nursing students in caring for critically-ill patients needing ALS. Educators must highly consider all parameters of simulation design and educational practices in planning and implementing HFS-based learning to achieve meaningful learner experience.}, } @article {pmid39071309, year = {2024}, author = {Yousefian-Jazi, A and Kim, S and Choi, SH and Chu, J and Nguyen, PT and Park, U and Lim, K and Hwang, H and Lee, K and Kim, Y and Hyeon, SJ and Rhim, H and Ryu, HL and Lim, G and Stein, TD and Ryu, H and Lee, J}, title = {Loss of MEF2C function by enhancer mutation leads to neuronal mitochondria dysfunction and motor deficits in mice.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2024.07.15.603186}, pmid = {39071309}, issn = {2692-8205}, support = {R01 NS109537/NS/NINDS NIH HHS/United States ; }, abstract = {Genetic changes and epigenetic modifications are associated with neuronal dysfunction in the pathogenesis of neurodegenerative disorders. However, the mechanism behind genetic mutations in the non-coding region of genes that affect epigenetic modifications remains unclear. Here, we identified an ALS-associated SNP located in the intronic region of MEF2C (rs304152), residing in a putative enhancer element, using convolutional neural network. The enhancer mutation of MEF2C reduces own gene expression and consequently impairs mitochondrial function in motor neurons. MEF2C localizes and binds to the mitochondria DNA, and directly modulates mitochondria-encoded gene expression. CRISPR/Cas-9-induced mutation of the MEF2C enhancer decreases expression of mitochondria-encoded genes. Moreover, MEF2C mutant cells show reduction of mitochondrial membrane potential, ATP level but elevation of oxidative stress. MEF2C deficiency in the upper and lower motor neurons of mice impairs mitochondria-encoded genes, and leads to mitochondrial metabolic disruption and progressive motor behavioral deficits. Together, MEF2C dysregulation by the enhancer mutation leads to mitochondrial dysfunction and oxidative stress, which are prevalent features in motor neuronal damage and ALS pathogenesis. This genetic and epigenetic crosstalk mechanism provides insights for advancing our understanding of motor neuron disease and developing effective treatments.}, } @article {pmid39071287, year = {2024}, author = {Tchounwou, C and Jobanputra, AJ and Lasher, D and Fletcher, BJ and Jacinto, J and Bhaduri, A and Best, RL and Fisher, WS and Ewert, KK and Li, Y and Feinstein, SC and Safinya, CR}, title = {Mixtures of Intrinsically Disordered Neuronal Protein Tau and Anionic Liposomes Reveal Distinct Anionic Liposome-Tau Complexes Coexisting with Tau Liquid-Liquid Phase Separated Coacervates.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {39071287}, issn = {2692-8205}, support = {R01 NS035010/NS/NINDS NIH HHS/United States ; }, abstract = {Tau, an intrinsically disordered neuronal protein and polyampholyte with an overall positive charge, is a microtubule (MT) associated protein, which binds to anionic domains of MTs and suppresses their dynamic instability. Aberrant tau-MT interactions are implicated in Alzheimer's and other neurodegenerative diseases. Here, we studied the interactions between full length human protein tau and other negatively charged binding substrates, as revealed by differential-interference-contrast (DIC) and fluorescence microscopy. As a binding substrate, we chose anionic liposomes (ALs) containing either 1,2-dioleoyl-sn-glycero-3-phosphatidylserine (DOPS, -1e) or 1,2-dioleoyl-sn-glycero-3-phosphatidylglycerol (DOPG, -1e) mixed with zwitterionic 1,2dioleoyl-sn-glycero-3-phosphatidylcholine (DOPC) to mimic anionic plasma membranes of axons where tau resides. At low salt concentrations (0 to 10 mM KCl or NaCl) with minimal charge screening, reaction mixtures of tau and ALs resulted in the formation of distinct states of AL-tau complexes coexisting with liquid-liquid phase separated tau self-coacervates arising from the polyampholytic nature of tau containing cationic and anionic domains. AL-tau complexes exhibited distinct types of morphologies. This included, large ≈20-30 micron tau-decorated giant vesicles with additional smaller liposomes with bound tau attached to the giant vesicles, and tau-mediated finite-size assemblies of small liposomes. As the ionic strength of the solution was increased to near and above physiological salt concentrations for 1:1 electrolytes (≈150 mM), AL-tau complexes remained stable while tau self-coacervate droplets were found to dissolve indicative of breaking of (anionic/cationic) electrostatic bonds between tau chains due to increased charge screening. The findings are consistent with the hypothesis that distinct cationic domains of tau may interact with anionic lipid domains of the lumen facing monolayer of the axon plasma membrane suggesting the possibility of transient yet robust interactions at physiologically relevant ionic strengths.}, } @article {pmid39070547, year = {2024}, author = {Kannan, A and Gangadharan Leela, S and Branzei, D and Gangwani, L}, title = {Role of senataxin in R-loop-mediated neurodegeneration.}, journal = {Brain communications}, volume = {6}, number = {4}, pages = {fcae239}, pmid = {39070547}, issn = {2632-1297}, support = {R01 NS115834/NS/NINDS NIH HHS/United States ; }, abstract = {Senataxin is an RNA:DNA helicase that plays an important role in the resolution of RNA:DNA hybrids (R-loops) formed during transcription. R-loops are involved in the regulation of biological processes such as immunoglobulin class switching, gene expression and DNA repair. Excessive accumulation of R-loops results in DNA damage and loss of genomic integrity. Senataxin is critical for maintaining optimal levels of R-loops to prevent DNA damage and acts as a genome guardian. Within the nucleus, senataxin interacts with various RNA processing factors and DNA damage response and repair proteins. Senataxin interactors include survival motor neuron and zinc finger protein 1, with whom it co-localizes in sub-nuclear bodies. Despite its ubiquitous expression, mutations in senataxin specifically affect neurons and result in distinct neurodegenerative diseases such as amyotrophic lateral sclerosis type 4 and ataxia with oculomotor apraxia type 2, which are attributed to the gain-of-function and the loss-of-function mutations in senataxin, respectively. In addition, low levels of senataxin (loss-of-function) in spinal muscular atrophy result in the accumulation of R-loops causing DNA damage and motor neuron degeneration. Senataxin may play multiple functions in diverse cellular processes; however, its emerging role in R-loop resolution and maintenance of genomic integrity is gaining attention in the field of neurodegenerative diseases. In this review, we highlight the role of senataxin in R-loop resolution and its potential as a therapeutic target to treat neurodegenerative diseases.}, } @article {pmid39069396, year = {2024}, author = {Codron, P and Millecamps, S and Corcia, P}, title = {EVolution in ALS diagnosis: molecular markers in extracellular vesicles.}, journal = {Trends in molecular medicine}, volume = {30}, number = {12}, pages = {1097-1099}, doi = {10.1016/j.molmed.2024.07.006}, pmid = {39069396}, issn = {1471-499X}, mesh = {*Amyotrophic Lateral Sclerosis/diagnosis/metabolism/genetics ; Humans ; *Extracellular Vesicles/metabolism ; *Biomarkers ; DNA-Binding Proteins/metabolism/genetics ; }, abstract = {The identification of biomarkers for amyotrophic lateral sclerosis (ALS) is a central issue in disease research. In a recent article, Chatterjee et al. show that blood extracellular vesicles (EVs) with high levels of transactive response DNA-binding protein 43 (TDP-43) accurately discriminate patients with ALS from controls and correlate with disease severity, providing a promising biomarker for early diagnosis and monitoring.}, } @article {pmid39069095, year = {2024}, author = {Ho, PC and Hsieh, TC and Tsai, KJ}, title = {TDP-43 proteinopathy in frontotemporal lobar degeneration and amyotrophic lateral sclerosis: From pathomechanisms to therapeutic strategies.}, journal = {Ageing research reviews}, volume = {100}, number = {}, pages = {102441}, doi = {10.1016/j.arr.2024.102441}, pmid = {39069095}, issn = {1872-9649}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism/pathology/genetics/therapy ; *Frontotemporal Lobar Degeneration/metabolism/pathology/therapy/genetics ; *TDP-43 Proteinopathies/metabolism/pathology/genetics ; *DNA-Binding Proteins/metabolism/genetics ; Animals ; Autophagy/physiology ; }, abstract = {Proteostasis failure is a common pathological characteristic in neurodegenerative diseases. Revitalizing clearance systems could effectively mitigate these diseases. The transactivation response (TAR) DNA-binding protein 43 (TDP-43) plays a critical role as an RNA/DNA-binding protein in RNA metabolism and synaptic function. Accumulation of TDP-43 aggregates in the central nervous system is a hallmark of frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). Autophagy, a major and highly conserved degradation pathway, holds the potential for degrading aggregated TDP-43 and alleviating FTLD/ALS. This review explores the causes of TDP-43 aggregation, FTLD/ALS-related genes, key autophagy factors, and autophagy-based therapeutic strategies targeting TDP-43 proteinopathy. Understanding the underlying pathological mechanisms of TDP-43 proteinopathy can facilitate therapeutic interventions.}, } @article {pmid39068922, year = {2024}, author = {Srivastava, K and Arshad, F and Mujawar, WJ and Cranberg, L and Rajeshwaran, J and Afsar, M and Thanissery, N and Desai, V and Keerthana, BS and Shubhangi, B and Vengalil, S and Nashi, S and Baskar, D and Polavarapu, K and Preethish-Kumar, V and Alladi, S and Nalini, A}, title = {Cognitive and Behavioral Profile of Patients with Amyotrophic Lateral Sclerosis Spectrum in the Indian Context.}, journal = {Dementia and geriatric cognitive disorders}, volume = {53}, number = {6}, pages = {310-320}, doi = {10.1159/000540018}, pmid = {39068922}, issn = {1421-9824}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/psychology/complications ; Male ; Female ; Middle Aged ; India/epidemiology ; *Frontotemporal Dementia/psychology ; *Neuropsychological Tests ; *Cognitive Dysfunction/psychology ; Aged ; Cognition/physiology ; Adult ; Executive Function ; Case-Control Studies ; }, abstract = {INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is characterized by motor, cognitive, and behavioral impairment. There is a paucity of evidence about the cognitive/behavioral features of ALS patients from India. We aimed to investigate the cognitive/behavioral profile of ALS spectrum disorders in the Indian context.

METHODS: Sixty patients with ALS spectrum and 40 age-, gender-, and education-matched healthy controls were recruited. The scales used were Addenbrooke's Cognitive Examination (ACE-III), Clinical Dementia Rating (CDR) scale, and Frontal Systems Behavior (FrSBe) Scale.

RESULTS: The mean age of the overall cohort was 55 years, and male-to-female ratio was 2.5:1. The mean duration of illness of the cohort was 16 months. Patients were classified as ALS with normal cognition (ALS-cn, n = 21), mild cognitive or behavioral deficits (ALS-ci/-bi, n = 28), and frontotemporal dementia (ALS-FTD, n = 11). ALS-cn had poorer scores compared to healthy controls in global cognition, memory, and language (p < 0.05). ALS-ci/-bi performed poorer than healthy controls on all cognitive domains (p < 0.05). ALS-FTD had poorer scores than healthy controls and ALS-cn on all cognitive domains (p < 0.001). Behavioral assessment showed an increase in apathy among all subtypes. ALS-FTD showed significant worsening in disinhibition and executive function compared to ALS-cn and ALS-ci/-bi.

CONCLUSION: Our findings suggest that there are key cognitive and behavior characteristics in Indian patients with ALS spectrum. This further strengthens the evidence of a cognitive continuum in ALS and FTD in a diverse context and highlights the importance of meticulous evaluation and correct diagnosis that would assist in better management.}, } @article {pmid39067491, year = {2024}, author = {Cheung, SW and Willis, EF and Simmons, DG and Bellingham, MC and Noakes, PG}, title = {Phagocytosis of aggrecan-positive perineuronal nets surrounding motor neurons by reactive microglia expressing MMP-9 in TDP-43[Q331K] ALS model mice.}, journal = {Neurobiology of disease}, volume = {200}, number = {}, pages = {106614}, doi = {10.1016/j.nbd.2024.106614}, pmid = {39067491}, issn = {1095-953X}, mesh = {Animals ; Mice ; *Aggrecans/metabolism ; *Amyotrophic Lateral Sclerosis/metabolism/genetics/pathology ; Disease Models, Animal ; DNA-Binding Proteins/metabolism/genetics ; *Matrix Metalloproteinase 9/metabolism ; Mice, Transgenic ; *Microglia/metabolism ; *Motor Neurons/metabolism/pathology ; *Phagocytosis/physiology ; Spinal Cord/metabolism/pathology ; }, abstract = {Perineuronal nets (PNNs) are extracellular matrix structures that surround excitable neurons and their proximal dendrites. PNNs play an important role in neuroprotection against oxidative stress. Oxidative stress within motor neurons can act as a trigger for neuronal death, and this has been implicated in motor neuron degeneration in amyotrophic lateral sclerosis (ALS). We therefore characterised PNNs around alpha motor neurons and the possible contributing cellular factors in the mutant TDP-43[Q331K] transgenic mouse, a slow onset ALS mouse model. PNNs around alpha motor neurons showed significant loss at mid-stage disease in TDP-43[Q331K] mice compared to wild type strain control mice. PNN loss coincided with an increased expression of matrix metallopeptidase-9 (MMP-9), an endopeptidase known to cleave PNNs, within the ventral horn. During mid-stage disease, increased numbers of microglia and astrocytes expressing MMP-9 were present in the ventral horn of TDP-43[Q331K] mice. In addition, TDP-43[Q331K] mice showed increased levels of aggrecan, a PNN component, in the ventral horn by microglia and astrocytes during this period. Elevated aggrecan levels within glia were accompanied by an increase in fractalkine expression, a chemotaxic protein responsible for the recruitment of microglia, in alpha motor neurons of onset and mid-stage TDP-43[Q331K] mice. Following PNN loss, alpha motor neurons in mid-stage TDP-43[Q331K] mice showed increased 3-nitrotyrosine expression, an indicator of protein oxidation. Together, our observations along with previous PNN research provide suggests a possible model whereby microglia and astrocytes expressing MMP-9 degrade PNNs surrounding alpha motor neurons in the TDP-43[Q331K] mouse. This loss of nets may expose alpha-motor neurons to oxidative damage leading to degeneration of the alpha motor neurons in the TDP-43[Q331K] ALS mouse model.}, } @article {pmid39066921, year = {2024}, author = {Guarnaccia, M and Morello, G and La Cognata, V and La Bella, V and Conforti, FL and Cavallaro, S}, title = {Increased copy-number variant load of associated risk genes in sporadic cases of amyotrophic lateral sclerosis.}, journal = {Cellular and molecular life sciences : CMLS}, volume = {81}, number = {1}, pages = {316}, pmid = {39066921}, issn = {1420-9071}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/pathology ; *DNA Copy Number Variations/genetics ; Female ; *Genetic Predisposition to Disease ; Middle Aged ; Male ; Aged ; Risk Factors ; Polymorphism, Single Nucleotide ; Adult ; Case-Control Studies ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is an age-related neurodegenerative disease characterized by selective loss of motor neurons in the brainstem and spinal cord. Several genetic factors have been associated to ALS, ranging from causal genes and potential risk factors to disease modifiers. The search for pathogenic variants in these genes has mostly focused on single nucleotide variants (SNVs) while relatively understudied and not fully elucidated is the contribution of structural variants, such as copy number variations (CNVs). Here, we applied an exon-centric aCGH method to investigate, in sporadic ALS patients, the load of CNVs in 131 genes previously associated to ALS. Our approach revealed that CNV load, defined as the total number of CNVs or their size, was significantly higher in ALS cases than controls. About 87% of patients harbored multiple CNVs in ALS-related genes, and 75% structural variants compromised genes directly implicated in ALS pathogenesis (C9orf72, CHCHD10, EPHA4, FUS, HNRNPA1, KIF5A, NEK1, OPTN, PFN1, SOD1, TARDBP, TBK1, UBQLN2, UNC13A, VAPB, VCP). CNV load was also associated to higher onset age and disease progression rate. Although the contribution of individual CNVs in ALS is still unknown, their extensive load in disease-related genes may have relevant implications for the diagnostic, prognostic and therapeutical management of this devastating disorder.}, } @article {pmid39066735, year = {2024}, author = {Reis, PVM and Vargas, BS and Rebelo, RA and Massafera, MP and Prado, FM and Oreliana, H and de Oliveira, HV and Freitas, FP and Ronsein, GE and Miyamoto, S and Di Mascio, P and Medeiros, MHG}, title = {Quantitative Analysis of Glutathione and Carnosine Adducts with 4-Hydroxy-2-nonenal in Muscle in a hSOD1[G93A] ALS Rat Model.}, journal = {Chemical research in toxicology}, volume = {37}, number = {8}, pages = {1306-1314}, pmid = {39066735}, issn = {1520-5010}, mesh = {Animals ; *Amyotrophic Lateral Sclerosis/metabolism ; *Aldehydes/metabolism/chemistry ; *Carnosine/metabolism ; *Glutathione/metabolism ; Rats ; *Disease Models, Animal ; Muscle, Skeletal/metabolism ; Humans ; Superoxide Dismutase/metabolism ; Male ; Chromatography, High Pressure Liquid ; Rats, Transgenic ; Superoxide Dismutase-1/metabolism ; Rats, Sprague-Dawley ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the dysfunction and death of motor neurons through multifactorial mechanisms that remain unclear. ALS has been recognized as a multisystemic disease, and the potential role of skeletal muscle in disease progression has been investigated. Reactive aldehydes formed as secondary lipid peroxidation products in the redox processes react with biomolecules, such as DNA, proteins, and amino acids, resulting in cytotoxic effects. 4-Hydroxy-2-nonenal (HNE) levels are elevated in the spinal cord motor neurons of ALS patients, and HNE-modified proteins have been identified in the spinal cord tissue of an ALS transgenic mice model, suggesting that reactive aldehydes can contribute to motor neuron degeneration in ALS. One biological pathway of aldehyde detoxification involves conjugation with glutathione (GSH) or carnosine (Car). Here, the detection and quantification of Car, GSH, GSSG (glutathione disulfide), and the corresponding adducts with HNE, Car-HNE, and GS-HNE, were performed in muscle and liver tissues of a hSOD1[G93A] ALS rat model by reverse-phase high-performance liquid chromatography coupled to electrospray ion trap tandem mass spectrometry in the selected reaction monitoring mode. A significant increase in the levels of GS-HNE and Car-HNE was observed in the muscle tissue of the end-stage ALS animals. Therefore, analyzing variations in the levels of these adducts in ALS animal tissue is crucial from a toxicological perspective and can contribute to the development of new therapeutic strategies.}, } @article {pmid39065892, year = {2024}, author = {Liu, K and Guan, X and Ren, X and Wu, J}, title = {Disciplining a Rubidium Atomic Clock Based on Adaptive Kalman Filter.}, journal = {Sensors (Basel, Switzerland)}, volume = {24}, number = {14}, pages = {}, pmid = {39065892}, issn = {1424-8220}, abstract = {Rubidium atomic clocks have been used extensively in various fields, with applications such as a core component of Global Navigation Satellite Systems (GNSS). However, they exhibit inherently poor long-term stability. This paper presents the development of a control system for rubidium atomic clocks. It introduces an adaptive Kalman filtering algorithm for the disciplining of a rubidium atomic clock, utilizing autocovariance least squares (ALS) to estimate the clock's noise parameters. The experimental results demonstrate that the proposed algorithm achieves a high estimation accuracy. The standard deviation of the clock error between the steered rubidium atomic clock 1 Pulse Per Second (1PPS) and Coordinated Universal Time (UTC) provided by the National Time Service Center (NTSC) is better than 2.568 nanoseconds(ns), with peak-to-peak values improving to within 11.358 ns. Notably, its frequency stability is reduced to 3.06 × 10[-13] @100,000 s. The results for the rubidium atomic clock demonstrate that the adaptive Kalman filtering algorithm proposed herein constitutes an accurate and effective control strategy for the rubidium atomic clock discipline.}, } @article {pmid39063341, year = {2024}, author = {Lagrange, E and Vernoux, JP and Chambon, C and Camu, W and Spencer, PS}, title = {Cramp-Fasciculation Syndrome Associated with Natural and Added Chemicals in Popular Food Items.}, journal = {Foods (Basel, Switzerland)}, volume = {13}, number = {14}, pages = {}, pmid = {39063341}, issn = {2304-8158}, abstract = {Cramp-fasciculation syndrome (CFS) is a rare and benign neuromuscular disorder that may initially masquerade as motor neuron disease/amyotrophic lateral sclerosis. While CFS may have a familial disposition, we report on cases associated with high consumption of popular food items. One set of patients reversibly experienced acute onset of headache, flushing, muscle stiffness and fasciculations following the consumption of umami-flavored food containing a large concentration of monosodium glutamate. A second group of patients consuming food derived from lupin seed developed acute cholinergic toxicity, CFS, and, with chronic intake, significant, self-limiting, but incompletely reversible upper and lower motor neuron deficits. While these cases may improve our knowledge about the possible causes of CFS, our series also demonstrates that excessive consumption of some popular foods is not harmless. This warrants further research on their safety at all stages of human development from a neurological point of view.}, } @article {pmid39063053, year = {2024}, author = {Alanazi, N and Fitzgerald, M and Hume, P and Hellewell, S and Horncastle, A and Anyaegbu, C and Papini, MG and Hargreaves, N and Halicki, M and Entwistle, I and Hind, K and Chazot, P}, title = {Concussion-Related Biomarker Variations in Retired Rugby Players and Implications for Neurodegenerative Disease Risk: The UK Rugby Health Study.}, journal = {International journal of molecular sciences}, volume = {25}, number = {14}, pages = {}, pmid = {39063053}, issn = {1422-0067}, mesh = {Humans ; *Biomarkers/blood ; Male ; *Brain Concussion/blood/epidemiology ; Middle Aged ; United Kingdom/epidemiology ; *Retirement ; *Football/injuries ; Adult ; *Athletes ; *Neurodegenerative Diseases/blood/epidemiology/etiology ; Rugby ; tau Proteins/blood ; Risk Factors ; Retinol-Binding Proteins, Plasma/metabolism ; Athletic Injuries/blood/epidemiology ; }, abstract = {The health and well-being of retired rugby union and league players, particularly regarding the long-term effects of concussions, are of major concern. Concussion has been identified as a major risk factor for neurodegenerative diseases, such as Alzheimer's and Amyotrophic Lateral Sclerosis (ALS), in athletes engaged in contact sports. This study aimed to assess differences in specific biomarkers between UK-based retired rugby players with a history of concussion and a non-contact sports group, focusing on biomarkers associated with Alzheimer's, ALS, and CTE. We randomly selected a sample of male retired rugby or non-contact sport athletes (n = 56). The mean age was 41.84 ± 6.44, and the mean years since retirement from the sport was 7.76 ± 6.69 for participants with a history of substantial concussions (>5 concussions in their career) (n = 30). The mean age was 45.75 ± 11.52, and the mean years since retirement was 6.75 ± 4.64 for the healthy controls (n = 26). Serum biomarkers (t-tau, RBP-4, SAA, Nf-L, and retinol), plasma cytokines, and biomarkers associated with serum-derived exosomes (Aβ42, p-tau181, p-tau217, and p-tau231) were analyzed using validated commercial ELISA assays. The results of the selected biomarkers were compared between the two groups. Biomarkers including t-tau and p-tau181 were significantly elevated in the history of the substantial concussion group compared to the non-contact sports group (t-tau: p < 0.01; p-tau181: p < 0.05). Although between-group differences in p-tau217, p-tau231, SAA, Nf-L, retinol, and Aβ42 were not significantly different, there was a trend for higher levels of Aβ42, p-tau217, and p-tau231 in the concussed group. Interestingly, the serum-derived exosome sizes were significantly larger (p < 0.01), and serum RBP-4 levels were significantly reduced (p < 0.05) in the highly concussed group. These findings indicate that retired athletes with a history of multiple concussions during their careers have altered serum measurements of exosome size, t-tau, p-tau181, and RBP-4. These biomarkers should be explored further for the prediction of future neurodegenerative outcomes, including ALS, in those with a history of concussion.}, } @article {pmid39062967, year = {2024}, author = {Kisielewska, M and Filipski, M and Sebastianka, K and Karaś, D and Molik, K and Choromańska, A}, title = {Investigation into the Neuroprotective and Therapeutic Potential of Plant-Derived Chk2 Inhibitors.}, journal = {International journal of molecular sciences}, volume = {25}, number = {14}, pages = {}, pmid = {39062967}, issn = {1422-0067}, mesh = {*Checkpoint Kinase 2/metabolism/antagonists & inhibitors ; Humans ; Animals ; Protein Kinase Inhibitors/pharmacology/therapeutic use/chemistry ; Neuroprotective Agents/pharmacology/therapeutic use ; Neoplasms/drug therapy ; DNA Damage/drug effects ; DNA Repair/drug effects ; }, abstract = {Nature provides us with a rich source of compounds with a wide range of applications, including the creation of innovative drugs. Despite advancements in chemically synthesized therapeutics, natural compounds are increasingly significant, especially in cancer treatment, a leading cause of death globally. One promising approach involves the use of natural inhibitors of checkpoint kinase 2 (Chk2), a critical regulator of DNA repair, cell cycle arrest, and apoptosis. Chk2's activation in response to DNA damage can lead to apoptosis or DNA repair, influencing glycolysis and mitochondrial function. In cancer therapy, inhibiting Chk2 can disrupt DNA repair and cell cycle progression, promoting cancer cell death and enhancing the efficacy of radiotherapy and chemotherapy. Additionally, Chk2 inhibitors can safeguard non-cancerous cells during these treatments by inhibiting p53-dependent apoptosis. Beyond oncology, Chk2 inhibition shows potential in treating hepatitis C virus (HCV) infections, as the virus relies on Chk2 for RNA replication in neurodegenerative diseases like amyotrophic lateral sclerosis (ALS), in which DNA damage plays a crucial role. Plant-derived Chk2 inhibitors, such as artemetin, rhamnetin, and curcumin, offer a promising future for treating various diseases with potentially milder side effects and broader metabolic impacts compared to conventional therapies. The review aims to underscore the immense potential of natural Chk2 inhibitors in various therapeutic contexts, particularly in oncology and the treatment of other diseases involving DNA damage and repair mechanisms. These natural Chk2 inhibitors hold significant promise for revolutionizing the landscape of cancer treatment and other diseases. Further research into these compounds could lead to the development of innovative therapies that offer hope for the future with fewer side effects and enhanced efficacy.}, } @article {pmid39062592, year = {2024}, author = {Gao, J and Sterling, E and Hankin, R and Sikal, A and Yao, Y}, title = {Therapeutics Targeting Skeletal Muscle in Amyotrophic Lateral Sclerosis.}, journal = {Biomolecules}, volume = {14}, number = {7}, pages = {}, pmid = {39062592}, issn = {2218-273X}, support = {W81XWH2210261//United States Department of Defense/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/metabolism/pathology/therapy ; Humans ; *Muscle, Skeletal/metabolism/pathology ; Animals ; Neuromuscular Junction/metabolism/pathology ; Motor Neurons/metabolism/pathology ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a complex neuromuscular disease characterized by progressive motor neuron degeneration, neuromuscular junction dismantling, and muscle wasting. The pathological and therapeutic studies of ALS have long been neurocentric. However, recent insights have highlighted the significance of peripheral tissue, particularly skeletal muscle, in disease pathology and treatment. This is evidenced by restricted ALS-like muscle atrophy, which can retrogradely induce neuromuscular junction and motor neuron degeneration. Moreover, therapeutics targeting skeletal muscles can effectively decelerate disease progression by modulating muscle satellite cells for muscle repair, suppressing inflammation, and promoting the recovery or regeneration of the neuromuscular junction. This review summarizes and discusses therapeutic strategies targeting skeletal muscles for ALS treatment. It aims to provide a comprehensive reference for the development of novel therapeutics targeting skeletal muscles, potentially ameliorating the progression of ALS.}, } @article {pmid39061876, year = {2024}, author = {Magalhães, RSS and Monteiro Neto, JR and Ribeiro, GD and Paranhos, LH and Eleutherio, ECA}, title = {Trehalose Protects against Superoxide Dismutase 1 Proteinopathy in an Amyotrophic Lateral Sclerosis Model.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {13}, number = {7}, pages = {}, pmid = {39061876}, issn = {2076-3921}, support = {PROBRAL 88881.371325/2019-01//Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)/ ; CNE 201.174/2022 and Posdoc Nota 10 202.267/2019//Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro/ ; Universal 401780/2023-6//National Council for Scientific and Technological Development/ ; }, abstract = {This work aimed to study the effect of trehalose in protecting cells against Sod1 proteinopathy associated with amyotrophic lateral sclerosis (ALS). Humanized yeast cells in which native Sod1 was replaced by wild-type human Sod1 or an ALS mutant (WT-A4V Sod1 heterodimer) were used as the experimental model. Cells were treated with 10% trehalose (p/v) before or after the appearance of hSod1 proteinopathy induced by oxidative stress. In both conditions, trehalose reduced the number of cells with Sod1 inclusions, increased Sod1 activity, and decreased the levels of intracellular oxidation, demonstrating that trehalose avoids Sod1 misfolding and loss of function in response to oxidative stress. The survival rates of ALS Sod1 cells stressed in the presence of trehalose were 60% higher than in their absence. Treatment with trehalose after the appearance of Sod1 inclusions in cells expressing WT Sod1 doubled longevity; after 5 days, non-treated cells did not survive, but 15% of cells treated with sugar were still alive. Altogether, our results emphasize the potential of trehalose as a novel therapy, which might be applied preventively in ALS patients with a family history of the disease or after diagnosis in ALS patients who discover the disease following the first symptoms.}, } @article {pmid39061402, year = {2024}, author = {Correia, JP and Gromicho, M and Pronto-Laborinho, AC and Oliveira Santos, M and de Carvalho, M}, title = {Creatine Kinase and Respiratory Decline in Amyotrophic Lateral Sclerosis.}, journal = {Brain sciences}, volume = {14}, number = {7}, pages = {}, pmid = {39061402}, issn = {2076-3425}, abstract = {Respiratory dysfunction is an important hallmark of amyotrophic lateral sclerosis (ALS). Elevation of creatine kinase (CK) has been reported in 23-75% of ALS patients, but the underlying mechanisms remain unknown. This work aims to enlighten the role of CK as a prognostic factor of respiratory dysfunction in ALS. A retrospective analysis of demographic and clinical variables, CK, functional decline per month (ΔFS), forced vital capacity (%FVC), and mean amplitude of the phrenic nerve compound motor action potential (pCMAP) in 319 ALS patients was conducted. These measurements were evaluated at study entry, and patients were followed from the moment of first observation until death or last follow-up visit. High CK values were defined as above the 90th percentile (CK ≥ P90) adjusted to sex. We analyzed survival and time to non-invasive ventilation (NIV) as proxies for respiratory impairment. Linear regression analysis revealed that high CK was associated with male sex (p < 0.001), spinal onset (p = 0.018), and FVC ≥ 80% (p = 0.038). CK was 23.4% higher in spinal-onset ALS patients (p < 0.001). High CK levels were not linked with an increased risk of death (p = 0.334) in Cox multivariate regression analysis. CK ≥ P90 (HR = 1.001, p = 0.038), shorter disease duration (HR = 0.937, p < 0.001), lower pCMAP (HR = 0.082, p < 0.001), and higher ΔFS (HR = 1.968, p < 0.001) were risk factors for respiratory failure. The association between high CK levels and poorer respiratory outcomes could derive from cellular metabolic stress or a specific phenotype associated with faster respiratory decline. Our study suggests that CK measurement at diagnosis should be more extensively investigated as a possible marker of poor respiratory outcome in future studies, including a larger population of patients.}, } @article {pmid39060907, year = {2025}, author = {Asai, Y and Yano, K and Higashino, T and Yoshihara, D and Sakiyama, H and Eguchi, H and Fukushima, K and Suzuki, K and Fujiwara, N}, title = {The Ile35 Residue of the ALS-Associated Mutant SOD1 Plays a Crucial Role in the Intracellular Aggregation of the Molecule.}, journal = {Molecular neurobiology}, volume = {62}, number = {2}, pages = {2023-2038}, pmid = {39060907}, issn = {1559-1182}, support = {22K11870//Japan Society for the Promotion of Science/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/genetics/enzymology/pathology ; Superoxide Dismutase-1 ; Humans ; *Mutation/genetics ; *Protein Aggregates ; *Superoxide Dismutase/genetics/metabolism/chemistry ; Animals ; *Intracellular Space/metabolism ; *Protein Aggregation, Pathological ; Green Fluorescent Proteins/metabolism ; *Mutant Proteins/metabolism/chemistry ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with an unknown pathogenesis. It has been reported that mutations in the gene for Cu/Zn superoxide dismutase (SOD1) cause familial ALS. Mutant SOD1 undergoes aggregation and forms amyloid more easily, and SOD1-immunopositive inclusions have been observed in the spinal cords of ALS patients. Because of this, SOD1 aggregation is thought to be related to the pathogenesis of ALS. Some core regions of amyloid have been identified, but the issue of whether these regions form aggregates in living cells remains unclear, and the mechanism responsible for intracellular SOD1 aggregation also remains unclear. The findings reported in this study indicate that the aggregation of the ALS-linked mutant SOD1-EGFP was significantly enhanced when the BioID2 gene was fused to the N-terminus of the mutant SOD1-EGFP plasmid for cellular expression. Expression of a series of BioID2-(C-terminal deletion peptides of SOD1)-EGFP permitted us to identify 1-35 as a minimal N-terminal sequence and Ile35 as an essential amino acid residue that contributes to the intracellular aggregation of SOD1. The findings also showed that an additional substitution of Ile35 with Ser into the ALS mutant SOD1 resulted in the significant suppression of aggregate formation. The fact that no Ile35 mutations have been reported to date in ALS patients indicates that all ALS mutant SOD1s contain Ile35. Taken together, we propose that Ile35 plays a pivotal role in the aggregation of the ALS-linked SOD1 and that this study will contribute to our understanding of the mechanism responsible for SOD1 aggregation.}, } @article {pmid39060854, year = {2024}, author = {Raymond, J and Nair, T and Gwathmey, KG and Larson, T and Horton, DK and Mehta, P}, title = {Racial Disparities in the Diagnosis and Prognosis of ALS Patients in the United States.}, journal = {Journal of racial and ethnic health disparities}, volume = {}, number = {}, pages = {}, pmid = {39060854}, issn = {2196-8837}, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive, fatal disease with largely unknown etiology. This study compares racial differences in clinical characteristics of ALS patients enrolled in the National ALS Registry (Registry).

METHODS: Data from ALS patients who completed the Registry's online clinical survey during 2013-2022 were analyzed to determine characteristics such as site of onset, associated symptoms, time of symptom onset to diagnosis, and pharmacological and non-pharmacological interventions for White, Black, and other race patients.

RESULTS: Surveys were completed by 4242 participants. Findings revealed that Black ALS patients were more likely to be diagnosed at a younger age, to have arm or hand initial site of onset, and to experience pneumonia than were White ALS patients. ALS patients of other races were more likely than White ALS patients to be diagnosed at a younger age and to experience twitching. The mean interval between the first sign of weakness and an ALS diagnosis for Black patients was almost 24 months, statistically greater than that of White (p = 0.0374; 16 months) and other race patients (p = 0.0518; 15.8 months). The mean interval between problems with speech until diagnosis was shorter for White patients (6.3 months) than for Black patients (17.7 months) and other race patients (14.8 months).

CONCLUSIONS AND RELEVANCE: Registry data shows racial disparities still exist in the diagnosis and clinical characteristics of ALS patients. Increased recruitment of non-White ALS patients and better characterization of symptom onset between races might aid clinicians in diagnosing ALS sooner, leading to earlier therapeutic interventions.}, } @article {pmid39060317, year = {2024}, author = {Wu, J and Zhang, G and Zhang, L and Ye, S and Huang, T and Fan, D}, title = {The integrity of the corticospinal tract and corpus callosum, and the risk of ALS: univariable and multivariable Mendelian randomization.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {17216}, pmid = {39060317}, issn = {2045-2322}, support = {81873784//National Natural Science Foundation of China/ ; BYSYDL2019002//Clinical Cohort Construction Program of Peking University Third Hospital/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/diagnostic imaging/pathology ; *Mendelian Randomization Analysis ; *Pyramidal Tracts/diagnostic imaging/pathology ; *Corpus Callosum/diagnostic imaging/pathology ; *Genome-Wide Association Study ; Risk Factors ; Male ; Female ; Genetic Predisposition to Disease ; Polymorphism, Single Nucleotide ; White Matter/diagnostic imaging/pathology ; Diffusion Magnetic Resonance Imaging ; Anisotropy ; }, abstract = {Studies suggest that amyotrophic lateral sclerosis (ALS) compromises the integrity of white matter fiber tracts, primarily affecting motor fibers. However, it remains uncertain whether the integrity of these fibers influences the risk of ALS. We performed bidirectional two-sample Mendelian randomization (MR) and multivariable MR analyses to evaluate the associative relationships between the integrity of fiber tracts [including the corticospinal tract (CST) and corpus callosum (CC)] and the risk of ALS. Genetic instrumental variables for specific fiber tracts were obtained from published genome-wide association studies (GWASs), including 33,292 European individuals from five diffusion magnetic resonance imaging (dMRI) datasets. Summary-level GWAS data for ALS were derived from 27,205 ALS patients and 110,881 controls. The MR results suggested that an increase in the first principal component (PC1) of fractional anisotropy (FA) in the genu of the CC (GCC) was correlated with an increased risk of ALS (PFDR = 0.001, odds ratio = 1.363, 95% confidence interval 1.178-1.577). Although other neuroimaging phenotypes [mean diffusivity in the CST, radial diffusivity (RD) in the CST, FA in the GCC, PC1 in the body of the CC (BCC), PC1 in the CST, and RD in the GCC] did not pass correction, they were also considered to have suggestive associations with the risk of ALS. No evidence revealed that ALS caused changes in the integrity of fiber tracts. In summary, the results of this study provide genetic support for the potential association between the integrity of specific fiber tracts and the risk of ALS. Greater fiber integrity in the GCC and BCC may be a risk factor for ALS, while greater fiber integrity in the CST may have a protective effect on ALS. This study provides insights into ALS development.}, } @article {pmid39060265, year = {2024}, author = {Doi, H and Kageyama, I and Katoh-Fukui, Y and Hattori, A and Fukami, M and Shimura, N}, title = {Homozygous 6-bp deletion of IGFALS in a prepubertal boy with short stature.}, journal = {Human genome variation}, volume = {11}, number = {1}, pages = {27}, pmid = {39060265}, issn = {2054-345X}, abstract = {Biallelic IGFALS variants lead to acid‒labile subunit (ALS) deficiency characterized by growth hormone resistance with or without delayed puberty. Here, we report a prepubertal boy with a homozygous 2-amino acid deletion within the fourth N-glycosylation motif (c.1103_1108del, p.N368_S370delinsT) associated with parental consanguinity. He showed short stature consistent with ALS deficiency. This case expands the mutation spectrum of IGFALS to include the elimination of only one N-glycosylation motif of ALS.}, } @article {pmid39059442, year = {2024}, author = {Kilim, O and Báskay, J and Biricz, A and Bedőházi, Z and Pollner, P and Csabai, I}, title = {Transfer learning may explain pigeons' ability to detect cancer in histopathology.}, journal = {Bioinspiration & biomimetics}, volume = {19}, number = {5}, pages = {}, doi = {10.1088/1748-3190/ad6825}, pmid = {39059442}, issn = {1748-3190}, mesh = {Animals ; *Columbidae/physiology ; *Neoplasms/pathology/diagnostic imaging ; *Neural Networks, Computer ; Machine Learning ; Flight, Animal/physiology ; }, abstract = {Pigeons' unexpected competence in learning to categorize unseen histopathological images has remained an unexplained discovery for almost a decade (Levensonet al2015PLoS One10e0141357). Could it be that knowledge transferred from their bird's-eye views of the earth's surface gleaned during flight contributes to this ability? Employing a simulation-based verification strategy, we recapitulate this biological phenomenon with a machine-learning analog. We model pigeons' visual experience during flight with the self-supervised pre-training of a deep neural network on BirdsEyeViewNet; our large-scale aerial imagery dataset. As an analog of the differential food reinforcement performed in Levensonet al's study 2015PLoS One10e0141357), we apply transfer learning from this pre-trained model to the same Hematoxylin and Eosin (H&E) histopathology and radiology images and tasks that the pigeons were trained and tested on. The study demonstrates that pre-training neural networks with bird's-eye view data results in close agreement with pigeons' performance. These results support transfer learning as a reasonable computational model of pigeon representation learning. This is further validated with six large-scale downstream classification tasks using H&E stained whole slide image datasets representing diverse cancer types.}, } @article {pmid39059407, year = {2024}, author = {van den Berg, LH and Rothstein, JD and Shaw, PJ and Babu, S and Benatar, M and Bucelli, RC and Genge, A and Glass, JD and Hardiman, O and Libri, V and Mobach, T and Oskarsson, B and Pattee, GL and Ravits, J and Shaw, CE and Weber, M and Zinman, L and Jafar-Nejad, P and Rigo, F and Lin, L and Ferguson, TA and Gotter, AL and Graham, D and Monine, M and Inra, J and Sinks, S and Eraly, S and Garafalo, S and Fradette, S}, title = {Safety, tolerability, and pharmacokinetics of antisense oligonucleotide BIIB078 in adults with C9orf72-associated amyotrophic lateral sclerosis: a phase 1, randomised, double blinded, placebo-controlled, multiple ascending dose study.}, journal = {The Lancet. Neurology}, volume = {23}, number = {9}, pages = {901-912}, doi = {10.1016/S1474-4422(24)00216-3}, pmid = {39059407}, issn = {1474-4465}, mesh = {Humans ; Male ; Female ; Middle Aged ; *Amyotrophic Lateral Sclerosis/drug therapy/genetics ; Double-Blind Method ; *C9orf72 Protein/genetics ; *Oligonucleotides, Antisense/pharmacokinetics/administration & dosage/adverse effects/pharmacology ; Aged ; Adult ; Dose-Response Relationship, Drug ; }, abstract = {BACKGROUND: Hexanucleotide repeat expansion of C9orf72 is a common genetic cause of amyotrophic lateral sclerosis (ALS). No C9orf72-targeted treatments are available. BIIB078 is an investigational antisense oligonucleotide targeting C9orf72 sense RNA. We aimed to assess the safety, tolerability, and pharmacokinetics of BIIB078 in participants with C9orf72-associated ALS.

METHODS: This phase 1, randomised controlled trial was done at 22 sites in six countries (Canada, Ireland, Netherlands, Switzerland, UK, and USA). Adults with ALS and a pathogenic repeat expansion in C9orf72 were randomly assigned within six cohorts, via Interactive Response Technology in a 3:1 ratio per cohort, to receive BIIB078 (5 mg, 10 mg, 20 mg, 35 mg, 60 mg, or 90 mg in cohorts 1-6, respectively) or placebo, via an intrathecal bolus injection. The treatment period consisted of three loading doses of study treatment, administered approximately once every 2 weeks, followed by monthly maintenance doses during a treatment period of about 3 months for cohorts 1-3 and about 6 months for cohorts 4-6. Patients and investigators were masked to treatment assignment. The primary endpoint was the incidence of adverse events and serious adverse events. This trial was registered with ClinicalTrials.gov (NCT03626012) and is completed.

FINDINGS: Between Sept 10, 2018, and Nov 17, 2021, 124 patients were screened for inclusion in the study. 18 patients were excluded and 106 participants were enrolled and randomly assigned to receive 5 mg (n=6), 10 mg (n=9), 20 mg (n=9), 35 mg (n=19), 60 mg (n=18), or 90 mg (n=18) of BIIB078, or placebo (n=27). 58 (55%) of 106 patients were female. All patients received at least one dose of study treatment and were included in all analyses. All participants had at least one adverse event; most adverse events were mild or moderate in severity and did not lead to treatment discontinuation. The most common adverse events in BIIB078-treated participants were falls, procedural pain, headache, and post lumbar puncture syndrome. 14 (18%) of 79 patients who received any dose of BIIB078 reported serious adverse events, compared with nine (33%) of 27 patients who received placebo. Five participants who received BIIB078 and three participants who received placebo had fatal adverse events: respiratory failure in a participant who received 10 mg BIIB078, ALS worsening in two participants who received 35 mg BIIB078, traumatic intracerebral haemorrhage in one participant who received 35 mg BIIB078, pulmonary embolism in one participant who received 60 mg BIIB078, and respiratory failure in three participants who received placebo. All deaths were assessed as not related to the study treatment by the reporting investigator.

INTERPRETATION: On the basis of these phase 1 study results, including secondary and exploratory findings showing no reduction in neurofilament levels and no benefit on clinical outcomes relative to the placebo cohort, BIIB078 clinical development has been discontinued. However, these results will be informative in furthering our understanding of the complex pathobiology of C9orf72-associated ALS.

FUNDING: Biogen.}, } @article {pmid39059406, year = {2024}, author = {Petri, S}, title = {Targeting C9orf72 in people with ALS.}, journal = {The Lancet. Neurology}, volume = {23}, number = {9}, pages = {850-852}, doi = {10.1016/S1474-4422(24)00284-9}, pmid = {39059406}, issn = {1474-4465}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics ; *C9orf72 Protein/genetics ; }, } @article {pmid39059260, year = {2024}, author = {Luo, L and Jiang, L and Chen, T and Zhao, Z and Kang, C and Chen, D and Long, Y}, title = {Analysis of spatiotemporal changes mechanism of cell wall biopolymers and monosaccharide components in kiwifruit during Botryosphaeria dothidea infection.}, journal = {Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy}, volume = {322}, number = {}, pages = {124837}, doi = {10.1016/j.saa.2024.124837}, pmid = {39059260}, issn = {1873-3557}, mesh = {*Cell Wall/chemistry ; *Ascomycota/chemistry ; *Plant Diseases/microbiology ; *Monosaccharides/analysis ; *Actinidia/microbiology/chemistry ; *Spectrum Analysis, Raman/methods ; Fruit/microbiology/chemistry ; Biopolymers/chemistry/analysis ; Pectins/chemistry/metabolism ; Polysaccharides ; }, abstract = {To further reveal the interaction mechanism between plants and pathogens, this study used confocal Raman microscopy spectroscopy (CRM) combined with chemometrics to visualize the biopolymers distribution of kiwifruit cell walls at different infection stages at the cellular micro level. Simultaneously, the changes in the content of various monosaccharides in fruit were studied at the molecular level using high-performance liquid chromatography (HPLC). There were significant differences in the composition of various nutrient components in the cell wall structure of kiwifruit at different infection times after infection by Botryosphaeria dothidea. PCA could cluster samples with infection time of 0-9 d into different infection stages, and SVM was used to predict the PCA classification results, the accuracy >96 %. Multivariate curve resolution-alternating least squares (MCR-ALS) helped to identify single substance spectra and concentration signals from mixed spectral signals. The pure substance chemical imaging maps of low methylated pectin (LMP), high methylated pectin (HMP), cellulose, hemicellulose, and lignin were obtained by analyzing the resolved concentration data. The imaging results showed that the lignin content in the kiwifruit cell wall increased significantly to resist pathogens infection after the infection of B. dothidea. With the development of infection, B. dothidea decomposed various substances in the host cell walls, allowing them to penetrate the interior of fruit cells. This caused significant changes in the form, structure, and distribution of various chemicals on the fruit cell walls in time and space. HPLC showed that glucose was the main carbon source and energy substance obtained by pathogens from kiwifruit during infection. The contents of galactose and arabinose, which maintained the structure and function of the fruit cell walls, decreased significantly and the cell wall structure was destroyed in the late stage of pathogens infection. This study provided a new perspective on the cellular structure changes caused by pathogenic infection of fruit and the defense response process of fruit and provided effective references for further research on the mechanisms of host-pathogen interactions in fruit infected by pathogens.}, } @article {pmid39059072, year = {2024}, author = {Grieco, I and Bassani, D and Trevisan, L and Salmaso, V and Cescon, E and Prencipe, F and Da Ros, T and Martinez-Gonzalez, L and Martinez, A and Spalluto, G and Moro, S and Federico, S}, title = {7-Amino-[1,2,4]triazolo[1,5-a][1,3,5]triazines as CK1δ inhibitors: Exploring substitutions at the 2 and 5-positions.}, journal = {Bioorganic chemistry}, volume = {151}, number = {}, pages = {107659}, doi = {10.1016/j.bioorg.2024.107659}, pmid = {39059072}, issn = {1090-2120}, mesh = {*Protein Kinase Inhibitors/pharmacology/chemistry/chemical synthesis ; Humans ; *Casein Kinase Idelta/antagonists & inhibitors/metabolism ; Structure-Activity Relationship ; Molecular Structure ; Triazines/chemistry/pharmacology/chemical synthesis ; Dose-Response Relationship, Drug ; Triazoles/chemistry/pharmacology/chemical synthesis ; Animals ; Neuroprotective Agents/pharmacology/chemistry/chemical synthesis ; Molecular Docking Simulation ; }, abstract = {CK1δ is a serine-threonine kinase involved in several pathological conditions including neuroinflammation and neurodegenerative disorders like Alzheimer's disease, Parkinson's disease, and Amyotrophic Lateral Sclerosis. Specifically, it seems that an inhibition of CK1δ could have a neuroprotective effect in these conditions. Here, a series of [1,2,4]triazolo[1,5-a][1,3,5]triazines were developed as ATP-competitive CK1δ inhibitors. Both positions 2 and 5 have been explored leading to a total of ten compounds exhibiting IC50s comprised between 29.1 µM and 2.08 µM. Three of the four most potent compounds (IC50 < 3 µM) bear a thiophene ring at the 2 position. All compounds have been submitted to computational studies that identified the chain composed of at least 2 atoms (e.g., nitrogen and carbon atoms) at the 5 position as crucial to determine a key bidentate hydrogen bond with Leu85 of CK1δ. Most potent compounds have been tested in vitro, resulting passively permeable to the blood-brain barrier and, safe and slight neuroprotective on a neuronal cell model. These results encourage to further structural optimize the series to obtain more potent CK1δ inhibitors as possible neuroprotective agents to be tested on models of the above-mentioned neurodegenerative diseases.}, } @article {pmid39058450, year = {2024}, author = {Baumgartner, D and Mušová, Z and Zídková, J and Hedvičáková, P and Vlčková, E and Joppeková, L and Kramářová, T and Fajkusová, L and Stránecký, V and Geryk, J and Votýpka, P and Mazanec, R}, title = {Genetic Landscape of Amyotrophic Lateral Sclerosis in Czech Patients.}, journal = {Journal of neuromuscular diseases}, volume = {11}, number = {5}, pages = {1035-1048}, pmid = {39058450}, issn = {2214-3602}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics ; Czech Republic ; Male ; Middle Aged ; Female ; *C9orf72 Protein/genetics ; Aged ; *DNA Repeat Expansion ; Adult ; *Frontotemporal Dementia/genetics ; RNA-Binding Protein FUS/genetics ; Cohort Studies ; DNA-Binding Proteins/genetics ; Protein Serine-Threonine Kinases/genetics ; Age of Onset ; Genetic Predisposition to Disease ; High-Throughput Nucleotide Sequencing ; }, abstract = {BACKGROUND: Genetic factors are involved in the pathogenesis of familial and sporadic amyotrophic lateral sclerosis (ALS) and constitute a link to its association with frontotemporal dementia (FTD). Gene-targeted therapies for some forms of ALS (C9orf72, SOD1) have recently gained momentum. Genetic architecture in Czech ALS patients has not been comprehensively assessed so far.

OBJECTIVE: We aimed to deliver pilot data on the genetic landscape of ALS in our country.

METHODS: A cohort of patients with ALS (n = 88), recruited from two Czech Neuromuscular Centers, was assessed for hexanucleotide repeat expansion (HRE) in C9orf72 and also for genetic variations in other 36 ALS-linked genes via next-generation sequencing (NGS). Nine patients (10.1%) had a familial ALS. Further, we analyzed two subgroups of sporadic patients - with concomitant FTD (n = 7) and with young-onset of the disease (n = 22).

RESULTS: We detected the pathogenic HRE in C9orf72 in 12 patients (13.5%) and three other pathogenic variants in FUS, TARDBP and TBK1, each in one patient. Additional 7 novel and 9 rare known variants with uncertain causal significance have been detected in 15 patients. Three sporadic patients with FTD (42.9%) were harbouring a pathogenic variant (all HRE in C9orf72). Surprisingly, none of the young-onset sporadic patients harboured a pathogenic variant and we detected no pathogenic SOD1 variant in our cohort.

CONCLUSION: Our findings resemble those from other European populations, with the highest prevalence of HRE in the C9orf72 gene. Further, our findings suggest a possibility of a missing genetic variability among young-onset patients.}, } @article {pmid39057679, year = {2024}, author = {Parvanovova, P and Hnilicova, P and Kolisek, M and Tatarkova, Z and Halasova, E and Kurca, E and Holubcikova, S and Koprusakova, MT and Baranovicova, E}, title = {Disturbances in Muscle Energy Metabolism in Patients with Amyotrophic Lateral Sclerosis.}, journal = {Metabolites}, volume = {14}, number = {7}, pages = {}, pmid = {39057679}, issn = {2218-1989}, support = {1/0371/21//VEGA/ ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neuromuscular disease type of motor neuron disorder characterized by degeneration of the upper and lower motor neurons resulting in dysfunction of the somatic muscles of the body. The ALS condition is manifested in progressive skeletal muscle atrophy and spasticity. It leads to death, mostly due to respiratory failure. Within the pathophysiology of the disease, muscle energy metabolism seems to be an important part. In our study, we used blood plasma from 25 patients with ALS diagnosed by definitive El Escorial criteria according to ALSFR-R (Revised Amyotrophic Lateral Sclerosis Functional Rating Scale) criteria and 25 age and sex-matched subjects. Aside from standard clinical biochemical parameters, we used the NMR (nuclear magnetic resonance) metabolomics approach to determine relative plasma levels of metabolites. We observed a decrease in total protein level in blood; however, despite accelerated skeletal muscle catabolism characteristic for ALS patients, we did not detect changes in plasma levels of essential amino acids. When focused on alterations in energy metabolism within muscle, compromised creatine uptake was accompanied by decreased plasma creatinine. We did not observe changes in plasma levels of BCAAs (branched chain amino acids; leucine, isoleucine, valine); however, the observed decrease in plasma levels of all three BCKAs (branched chain alpha-keto acids derived from BCAAs) suggests enhanced utilization of BCKAs as energy substrate. Glutamine, found to be increased in blood plasma in ALS patients, besides serving for ammonia detoxification, could also be considered a potential TCA (tricarboxylic acid) cycle contributor in times of decreased pyruvate utilization. When analyzing the data by using a cross-validated Random Forest algorithm, it finished with an AUC of 0.92, oob error of 8%, and an MCC (Matthew's correlation coefficient) of 0.84 when relative plasma levels of metabolites were used as input variables. Although the discriminatory power of the system used was promising, additional features are needed to create a robust discriminatory model.}, } @article {pmid39056697, year = {2024}, author = {Christidi, F and Kleinerova, J and Tan, EL and Delaney, S and Tacheva, A and Hengeveld, JC and Doherty, MA and McLaughlin, RL and Hardiman, O and Siah, WF and Chang, KM and Lope, J and Bede, P}, title = {Limbic Network and Papez Circuit Involvement in ALS: Imaging and Clinical Profiles in GGGGCC Hexanucleotide Carriers in C9orf72 and C9orf72-Negative Patients.}, journal = {Biology}, volume = {13}, number = {7}, pages = {}, pmid = {39056697}, issn = {2079-7737}, support = {JPND-Cofund-2-2019-1 & HRB EIA-2017-019//HRB/ ; }, abstract = {Background: While frontotemporal involvement is increasingly recognized in Amyotrophic lateral sclerosis (ALS), the degeneration of limbic networks remains poorly characterized, despite growing evidence of amnestic deficits, impaired emotional processing and deficits in social cognition. Methods: A prospective neuroimaging study was conducted with 204 individuals with ALS and 111 healthy controls. Patients were stratified for hexanucleotide expansion status in C9orf72. A deep-learning-based segmentation approach was implemented to segment the nucleus accumbens, hypothalamus, fornix, mammillary body, basal forebrain and septal nuclei. The cortical, subcortical and white matter components of the Papez circuit were also systematically evaluated. Results: Hexanucleotide repeat expansion carriers exhibited bilateral amygdala, hypothalamus and nucleus accumbens atrophy, and C9orf72 negative patients showed bilateral basal forebrain volume reductions compared to controls. Both patient groups showed left rostral anterior cingulate atrophy, left entorhinal cortex thinning and cingulum and fornix alterations, irrespective of the genotype. Fornix, cingulum, posterior cingulate, nucleus accumbens, amygdala and hypothalamus degeneration was more marked in C9orf72-positive ALS patients. Conclusions: Our results highlighted that mesial temporal and parasagittal subcortical degeneration is not unique to C9orf72 carriers. Our radiological findings were consistent with neuropsychological observations and highlighted the importance of comprehensive neuropsychological testing in ALS, irrespective of the underlying genotype.}, } @article {pmid39056295, year = {2025}, author = {Lindamood, HL and Liu, TM and Read, TA and Vitriol, EA}, title = {Using ALS to understand profilin 1's diverse roles in cellular physiology.}, journal = {Cytoskeleton (Hoboken, N.J.)}, volume = {82}, number = {3}, pages = {111-129}, pmid = {39056295}, issn = {1949-3592}, support = {R35 GM137959/GM/NIGMS NIH HHS/United States ; }, mesh = {*Profilins/metabolism/genetics ; Humans ; *Amyotrophic Lateral Sclerosis/metabolism/genetics/pathology ; Animals ; }, abstract = {Profilin is an actin monomer-binding protein whose role in actin polymerization has been studied for nearly 50 years. While its principal biochemical features are now well understood, many questions remain about how profilin controls diverse processes within the cell. Dysregulation of profilin has been implicated in a broad range of human diseases, including neurodegeneration, inflammatory disorders, cardiac disease, and cancer. For example, mutations in the profilin 1 gene (PFN1) can cause amyotrophic lateral sclerosis (ALS), although the precise mechanisms that drive neurodegeneration remain unclear. While initial work suggested proteostasis and actin cytoskeleton defects as the main pathological pathways, multiple novel functions for PFN1 have since been discovered that may also contribute to ALS, including the regulation of nucleocytoplasmic transport, stress granules, mitochondria, and microtubules. Here, we will review these newly discovered roles for PFN1, speculate on their contribution to ALS, and discuss how defects in actin can contribute to these processes. By understanding profilin 1's involvement in ALS pathogenesis, we hope to gain insight into this functionally complex protein with significant influence over cellular physiology.}, } @article {pmid39054893, year = {2024}, author = {Rajput, SS and Singh, SB and Subramanyam, D and Patil, S}, title = {Soft glassy rheology of single cells with pathogenic protein aggregates.}, journal = {Soft matter}, volume = {20}, number = {31}, pages = {6266-6274}, doi = {10.1039/d4sm00595c}, pmid = {39054893}, issn = {1744-6848}, mesh = {*Rheology ; Animals ; *Hemocytes/metabolism ; Protein Aggregates ; Viscosity ; Endocytosis ; Actins/metabolism/chemistry ; Single-Cell Analysis ; Microscopy, Atomic Force ; }, abstract = {A correlation between the mechanical properties of cells and various diseases has been emerging in recent years. Atomic force microscopy (AFM) has been widely used to measure a single cell's apparent Young's modulus by treating it as a fully elastic object. More recently, quantitative characterization of the complete viscoelasticity of single cells has become possible. We performed AFM-based nano-indentation experiments on hemocytes isolated from third instar larvae to determine their viscoelasticity and found that live hemocytes, like many other cells, follow a scale-free power-law rheology (PLR) akin to soft glasses. Further, we examined the changes in the rheological response of hemocytes in the presence of pathogenic protein aggregates known to cause neurodegenerative diseases such as Huntington's disorder and amyotrophic lateral sclerosis. Our results show that cells lose their fluidity and appear more solid-like in the presence of certain aggregates, in a manner correlated to actin reorganization. More solid-like cells also display reduced intracellular transport through clathrin-mediated endocytosis (CME). However, the cell's rheology remains largely unaffected and is similar to that of wild-type (WT) hemocytes, if aggregates do not perturb the actin organization and CME. Moreover, the fluid-like nature was significantly recovered when actin organization was rescued by overexpressing specific actin interacting proteins or chaperones. Our study, for the first time, underscores a direct correlation between parameters governing glassy dynamics, actin organization and CME.}, } @article {pmid39054501, year = {2024}, author = {Rahimi Darehbagh, R and Seyedoshohadaei, SA and Ramezani, R and Rezaei, N}, title = {Stem cell therapies for neurological disorders: current progress, challenges, and future perspectives.}, journal = {European journal of medical research}, volume = {29}, number = {1}, pages = {386}, pmid = {39054501}, issn = {2047-783X}, mesh = {Humans ; *Nervous System Diseases/therapy ; *Stem Cell Transplantation/methods/trends ; Animals ; Cell- and Tissue-Based Therapy/methods/trends ; Neural Stem Cells/transplantation/physiology ; }, abstract = {Stem cell-based therapies have emerged as a promising approach for treating various neurological disorders by harnessing the regenerative potential of stem cells to restore damaged neural tissue and circuitry. This comprehensive review provides an in-depth analysis of the current state of stem cell applications in primary neurological conditions, including Parkinson's disease (PD), Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), stroke, spinal cord injury (SCI), and other related disorders. The review begins with a detailed introduction to stem cell biology, discussing the types, sources, and mechanisms of action of stem cells in neurological therapies. It then critically examines the preclinical evidence from animal models and early human trials investigating the safety, feasibility, and efficacy of different stem cell types, such as embryonic stem cells (ESCs), mesenchymal stem cells (MSCs), neural stem cells (NSCs), and induced pluripotent stem cells (iPSCs). While ESCs have been studied extensively in preclinical models, clinical trials have primarily focused on adult stem cells such as MSCs and NSCs, as well as iPSCs and their derivatives. We critically assess the current state of research for each cell type, highlighting their potential applications and limitations in different neurological conditions. The review synthesizes key findings from recent, high-quality studies for each neurological condition, discussing cell manufacturing, delivery methods, and therapeutic outcomes. While the potential of stem cells to replace lost neurons and directly reconstruct neural circuits is highlighted, the review emphasizes the critical role of paracrine and immunomodulatory mechanisms in mediating the therapeutic effects of stem cells in most neurological disorders. The article also explores the challenges and limitations associated with translating stem cell therapies into clinical practice, including issues related to cell sourcing, scalability, safety, and regulatory considerations. Furthermore, it discusses future directions and opportunities for advancing stem cell-based treatments, such as gene editing, biomaterials, personalized iPSC-derived therapies, and novel delivery strategies. The review concludes by emphasizing the transformative potential of stem cell therapies in revolutionizing the treatment of neurological disorders while acknowledging the need for rigorous clinical trials, standardized protocols, and multidisciplinary collaboration to realize their full therapeutic promise.}, } @article {pmid39054363, year = {2024}, author = {Weishaupt, JH and Körtvélyessy, P and Schumann, P and Valkadinov, I and Weyen, U and Hesebeck-Brinckmann, J and Weishaupt, K and Endres, M and Andersen, PM and Regensburger, M and Dreger, M and Koch, JC and Conrad, J and Meyer, T}, title = {Tofersen decreases neurofilament levels supporting the pathogenesis of the SOD1 p.D91A variant in amyotrophic lateral sclerosis patients.}, journal = {Communications medicine}, volume = {4}, number = {1}, pages = {150}, pmid = {39054363}, issn = {2730-664X}, abstract = {BACKGROUND: Since the antisense oligonucleotide tofersen has recently become available for the treatment of amyotrophic lateral sclerosis (ALS) caused by mutations in SOD1, determining the causality of the over 230 SOD1 variants has become even more important. The most common SOD1 variant worldwide is p.D91A (c.272A > C), whose causality for ALS is contested when in a heterozygous state. The reason is the high allele frequency of SOD1[D91A] in Europe, exceeding 1% in Finno-Scandinavia.

METHODS: We present the clinical disease course and serum neurofilament light chain (NfL) results of treating 11 patients either homo- or heterozygous for the SOD1[D91A] allele for up to 16 months with tofersen.

RESULTS: Tofersen decreases serum neurofilament levels (sNFL), which are associated with the ALS progression rate, in the 6 ALS patients homozygous for SOD1[D91A]. We observe significantly lower sNfL levels in the 5 patients heterozygous for SOD1[D91A]. The results indicate that both mono- and bi-allelic SOD1[D91A] are causally relevant targets, with a possibly reduced effect size of SOD1[D91Ahet].

CONCLUSIONS: The finding is relevant for decision making regarding tofersen treatment, patient counseling and inclusion of SOD1[D91A] patients in drug trials. As far as we are aware, the approach is conceptually new since it provides evidence for the causality of an ALS variant based on a biomarker response to gene-specific treatment.}, } @article {pmid39054069, year = {2024}, author = {Wong, HC and Lang, AE and Stein, C and Drerup, CM}, title = {ALS-Linked VapB P56S Mutation Alters Neuronal Mitochondrial Turnover at the Synapse.}, journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, volume = {44}, number = {35}, pages = {}, pmid = {39054069}, issn = {1529-2401}, support = {R01 NS124692/NS/NINDS NIH HHS/United States ; T32 GM007133/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; *Zebrafish ; *Mitochondria/metabolism/genetics ; *Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology ; *Synapses/metabolism/genetics ; *Animals, Genetically Modified ; Vesicular Transport Proteins/genetics/metabolism ; Neurons/metabolism ; Humans ; Mutation ; Endoplasmic Reticulum/metabolism/genetics ; Mitophagy/genetics/physiology ; Zebrafish Proteins/genetics/metabolism ; }, abstract = {Mitochondrial population maintenance in neurons is essential for neuron function and survival. Contact sites between mitochondria and the endoplasmic reticulum (ER) are poised to regulate mitochondrial homeostasis in neurons. These contact sites can facilitate transfer of calcium and lipids between the organelles and have been shown to regulate aspects of mitochondrial dynamics. Vesicle-associated membrane protein-associated protein B (VapB) is an ER membrane protein present at a subset of ER-mitochondrial contact sites. A proline-to-serine mutation in VapB at amino acid 56 (P56S) correlates with susceptibility to amyotrophic lateral sclerosis (ALS) type 8. Given the relationship between failed mitochondrial health and neurodegenerative disease, we investigated the function of VapB in mitochondrial population maintenance. We demonstrated that transgenic expression of VapB[P56S] in zebrafish larvae (sex undetermined) increased mitochondrial biogenesis, causing increased mitochondrial population size in the axon terminal. Expression of wild-type VapB did not alter biogenesis but, instead, increased mitophagy in the axon terminal. Using genetic manipulations to independently increase mitochondrial biogenesis, we show that biogenesis is normally balanced by mitophagy to maintain a constant mitochondrial population size. VapB[P56S] transgenics fail to increase mitophagy to compensate for the increase in mitochondrial biogenesis, suggesting an impaired mitophagic response. Finally, using a synthetic ER-mitochondrial tether, we show that VapB's function in mitochondrial turnover is likely independent of ER-mitochondrial tethering by contact sites. Our findings demonstrate that VapB can control mitochondrial turnover in the axon terminal, and this function is altered by the P56S ALS-linked mutation.}, } @article {pmid39053342, year = {2024}, author = {Hideyama, T and Teramoto, S and Kato, H and Terashi, H and Kwak, S and Aizawa, H}, title = {Negative features of sporadic amyotrophic lateral sclerosis: Motor neurons of Onuf's nucleus survive in ADAR2-conditional knockout mice.}, journal = {Journal of the neurological sciences}, volume = {463}, number = {}, pages = {123142}, doi = {10.1016/j.jns.2024.123142}, pmid = {39053342}, issn = {1878-5883}, mesh = {Animals ; *Amyotrophic Lateral Sclerosis/genetics/pathology ; *Adenosine Deaminase/genetics/deficiency/metabolism ; *Motor Neurons/pathology/metabolism ; *RNA-Binding Proteins/genetics/metabolism ; Mice ; *Mice, Knockout ; DNA-Binding Proteins/genetics/metabolism ; Disease Models, Animal ; Receptors, AMPA/genetics/metabolism ; Mice, Transgenic ; }, abstract = {Patients with amyotrophic lateral sclerosis (ALS) do not develop oculomotor disturbances and vesicorectal dysfunction until end-stage disease owing to the survival of certain motor neurons (MNs), including oculomotor neurons and MNs within Onuf's nucleus. In sporadic ALS, adenosine deaminase acting on RNA 2 (ADAR2)-mediated editing of GluA2 mRNA at the Q/R site is compromised in lower MNs. We previously developed genetically modified mice with a conditional knockout of ADAR2 in cholinergic neurons (ADAR2[flox/flox]/VAChT-Cre, Fast; AR2). These mice displayed slow and progressive lower motor neuron death with TAR DNA-binding protein 43 (TDP-43) pathology, attributable to insufficient editing at the GluA2 Q/R site due to ADAR2 deficiency. MN death was more common in fast-fatigable MNs owing to differential vulnerability under conditions of ADAR2 deficiency. Although facial and hypoglossal nerves were impaired in AR2 mice, cell death did not occur within the oculomotor nerve nucleus, as observed in patients with sporadic ALS. Since the basis for avoiding cystorectal damage in ALS is unknown, we compared the features of Onuf's nucleus MNs in 12-month-old AR2 mice with those in age-matched wild-type mice. Although the number of MNs was not significantly lower in AR2 mice, the neurons exhibited a shrunken morphology and TDP-43 pathology. Onuf's nucleus MNs could survive in an ADAR2-deficient state and mainly included fast fatigue-resistant (FR) and slow (S) MNs. In summary, FR and S MNs show increased resilience to ADAR2 deficiency, potentially participating in an important neuronal death avoidance mechanism in ALS.}, } @article {pmid39050823, year = {2024}, author = {Min, JH and Sarlus, H and Harris, RA}, title = {Copper toxicity and deficiency: the vicious cycle at the core of protein aggregation in ALS.}, journal = {Frontiers in molecular neuroscience}, volume = {17}, number = {}, pages = {1408159}, pmid = {39050823}, issn = {1662-5099}, abstract = {The pathophysiology of ALS involves many signs of a disruption in copper homeostasis, with both excess free levels and functional deficiency likely occurring simultaneously. This is crucial, as many important physiological functions are performed by cuproenzymes. While it is unsurprising that many ALS symptoms are related to signs of copper deficiency, resulting in vascular, antioxidant system and mitochondrial oxidative respiration deficiencies, there are also signs of copper toxicity such as ROS generation and enhanced protein aggregation. We discuss how copper also plays a key role in proteostasis and interacts either directly or indirectly with many of the key aggregate-prone proteins implicated in ALS, such as TDP-43, C9ORF72, SOD1 and FUS as well as the effect of their aggregation on copper homeostasis. We suggest that loss of cuproprotein function is at the core of ALS pathology, a condition that is driven by a combination of unbound copper and ROS that can either initiate and/or accelerate protein aggregation. This could trigger a positive feedback cycle whereby protein aggregates trigger the aggregation of other proteins in a chain reaction that eventually captures elements of the proteostatic mechanisms in place to counteract them. The end result is an abundance of aggregated non-functional cuproproteins and chaperones alongside depleted intracellular copper stores, resulting in a general lack of cuproenzyme function. We then discuss the possible aetiology of ALS and illustrate how strong risk factors including environmental toxins such as BMAA and heavy metals can functionally behave to promote protein aggregation and disturb copper metabolism that likely drives this vicious cycle in sporadic ALS. From this synthesis, we propose restoration of copper balance using copper delivery agents in combination with chaperones/chaperone mimetics, perhaps in conjunction with the neuroprotective amino acid serine, as a promising strategy in the treatment of this incurable disease.}, } @article {pmid39050003, year = {2024}, author = {Özaydin Aksun, Z and Erdoğan, S and Kalkanci, A and Şahin, EA and Çuhadar, T and Şener, HÖ}, title = {Is gut microbiota of patients with ALS different from that of healthy individuals?.}, journal = {Turkish journal of medical sciences}, volume = {54}, number = {3}, pages = {579-587}, pmid = {39050003}, issn = {1303-6165}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/microbiology ; *Gastrointestinal Microbiome/genetics/physiology ; Female ; Male ; Middle Aged ; Adult ; Feces/microbiology ; RNA, Ribosomal, 16S/analysis/genetics ; Aged ; Case-Control Studies ; }, abstract = {BACKGROUND/AIM: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease. Several studies have shown that alterations of microbiota increase the risk of neurodegenerative disorders. We aimed to reveal whether there is a difference in the gut microbiota of patients with ALS.

MATERIALS AND METHODS: The participants are divided into three groups. Group 1 comprised patients with ALS. Healthy family members living in the same house of the patients formed Group 2. Lastly, sex- and age-matched healthy people were included in Group 3. Fecal samples were collected in 15-mL falcon tubes and stored at -80 °C. Genomic DNA isolation was performed on samples. Bacterial primers selected from the 16S rRNA region for the bacterial genome and ITS1 and ITS4 (internal transcribed spacer) were used for the identification of DNA. Next generation sequence analysis (NGS) and taxonomic analyses were performed at the level of bacterial phylum, class, order, family, genus, and species. Alpha and beta diversity indexes were used. The linear discriminant analysis (LDA) effect size method (LEfSe) was applied to identify a microbial taxon specific to ALS disease.

RESULTS: The relative abundances of the Succinivibrionaceae and Lachnospiraceae families were significantly lower in patients. The dominant families among patients were Streptococcaceae and Ruminococcaceae, while the dominant families among healthy controls were Bacteroidaceae and Succinivibrionaceae. The LEfSe analysis revealed that four families (Atopobiaceae, Actinomycetaceae, Erysipelatoclostridiaceae, Peptococcacceae) differed significantly between the patients and healthy controls (LDA values> 2.5, p < 0.05).

CONCLUSION: Comparison with family members living in the same house is the strength of this study. We found that there were changes in the microbiota of the patients, consistent with the literature. Studies that analyze the composition of the gut microbiota in the predisease period may be needed to understand whether dysbiosis is caused by the mechanisms inherent in the disease or whether it is dysbiosis that initiates the disease.}, } @article {pmid39047759, year = {2024}, author = {Schmid, G and Schneeweiss, P and Hirtl, R and Jhala, T and Samaras, T}, title = {Numerical assessment of induced electric fields in a worker's hand with commonly used metallic implants under exposure to low frequency magnetic fields.}, journal = {Journal of radiological protection : official journal of the Society for Radiological Protection}, volume = {44}, number = {3}, pages = {}, doi = {10.1088/1361-6498/ad66dc}, pmid = {39047759}, issn = {1361-6498}, mesh = {Humans ; *Occupational Exposure/analysis ; *Hand ; *Electromagnetic Fields ; Metals ; Magnetic Fields ; Prostheses and Implants ; Bone Screws ; Bone Plates ; }, abstract = {The European Union's Workers' Directive 2013/35/EU on the minimum health and safety requirements regarding the exposure of workers to electromagnetic fields specifies action levels (ALs) for external electric and magnetic fields, which should protect against induced tissue-internal electric field strengthEiabove the exposure limit values, the latter being defined in order to prevent tissue stimulation at low frequencies. However, although 2013/35/EU explicitly calls for the protection of 'workers at particular risk' (including workers with metallic implants), the AL specified in the Directive have been derived under the assumption that there are no metallic parts present inside the body. Therefore, in the present work, we analysed the situation of a worker's hand and forearm bearing metallic implants (Herbert screw and volar radius plate) used for osteosynthesis after the most common bone fractures of the hand/forearm, exposed to low frequency magnetic fields. The uniform exposure of the whole hand and forearm as well as the exposure to a specific and widely used device, a deactivator for single-use labels of acousto-magnetic electronic article surveillance systems, were considered based on numerical computations using a high-resolution anatomical hand and forearm model. The results obtained indicated that the maximum induced electric field strength averaged in a volume of 2 mm × 2 mm × 2 mm cube was higher in the presence of the metallic implants by a factor of up to 4.2 for bone tissue and 2.3 for soft tissue compared with the case without an implant. Hence, it is obvious that the local induced electric field strengths may be substantially increased by the implants. The extent of this increase, however, is highly dependent on the implant's position inside the body, the implant's geometry, and the field distribution and orientation with respect to the anatomical structure and the implant.}, } @article {pmid39046818, year = {2024}, author = {Brink, V and Kirkbride, J}, title = {Reply to Zhou et al's "Refining Psychosis Research: Insights on Cannabis Use and Data Accuracy".}, journal = {Schizophrenia bulletin}, volume = {50}, number = {5}, pages = {965-967}, pmid = {39046818}, issn = {1745-1701}, support = {//European Community's Seventh Framework/ ; 2012/0417-0//São Paulo Research Foundation/ ; MD-PhD 18-41//University Medical Centre Groningen/ ; //National Institute for Health and Care Research/ ; //University College London Hospitals NHS Foundation Trust/ ; //UK Research and Innovation/ ; MR/W030608/1//Clinical Academic Research Partnership/ ; }, mesh = {Humans ; *Psychotic Disorders ; Data Accuracy ; Biomedical Research/standards ; Marijuana Use/epidemiology ; Marijuana Abuse/epidemiology ; }, } @article {pmid39045865, year = {2024}, author = {Sanpei, Y and Yasuda, K and Takahashi, Y and Hanazono, A and Sugawara, M and Iijima, K}, title = {Evaluation of the applicability of weak shoulder and arm sparing signs in amyotrophic lateral sclerosis by multiple neurologists and neurology residents: A single-center study.}, journal = {Muscle & nerve}, volume = {70}, number = {4}, pages = {761-765}, doi = {10.1002/mus.28216}, pmid = {39045865}, issn = {1097-4598}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/physiopathology ; Male ; Female ; Middle Aged ; Aged ; *Shoulder/physiopathology ; Retrospective Studies ; *Arm/physiopathology ; *Neurologists ; *Muscle Weakness/diagnosis/physiopathology ; Internship and Residency ; Neurology/education ; Muscle, Skeletal/physiopathology ; Adult ; Sensitivity and Specificity ; Aged, 80 and over ; }, abstract = {INTRODUCTION/AIMS: Amyotrophic lateral sclerosis (ALS) exhibits selective muscle weakness. The weak shoulder and arm sparing signs, assessed by a single experienced neurologist, have been reported to be superior to previous signs in sensitivity and specificity. However, it is unknown whether the same results are observed when assessed by multiple neurologists.

METHODS: Subjects were retrospectively identified from our department's inpatient database from 2014 to 2023. Medical Research Council (MRC) scores of the deltoid (Del), biceps brachii (BB), triceps brachii (TB), and first dorsal interosseous (FDI) muscles were evaluated. The weak shoulder sign was defined as positive when Del was weaker than BB and TB. The arm sparing sign was defined as positive when both Del and FDI were weaker than BB and TB. Sensitivity was analyzed in all ALS patients and in subgroups based on the region of symptom onset, presence or absence of upper motor neuron (UMN) signs, and the Japanese ALS Severity Classification.

RESULTS: Seventy-one patients with ALS were identified. Eight neurologists and three neurology residents evaluated each patient's MRC scores. The weak shoulder and arm sparing signs were observed in 72% and 48% of patients, respectively, with no significant difference in sensitivity across patient subgroups.

DISCUSSION: The weak shoulder and arm sparing signs showed high and moderate sensitivity, respectively, consistent with a previous report, even when evaluated by multiple examiners. This expands the clinical utility and increases the reliability of these signs, potentially contributing to accurate ALS diagnosis when combined with other clinical features and objective assessments.}, } @article {pmid39044591, year = {2024}, author = {Wang, J and Feng, L and Zhang, Y and Xu, P}, title = {[Establishment of a stable THP-1 cell line expressing PSMB9-eGFP-His protein and detection of immunoproteasome activity].}, journal = {Sheng wu gong cheng xue bao = Chinese journal of biotechnology}, volume = {40}, number = {7}, pages = {2282-2293}, doi = {10.13345/j.cjb.240124}, pmid = {39044591}, issn = {1872-2075}, mesh = {Humans ; *Proteasome Endopeptidase Complex/genetics/metabolism ; *Green Fluorescent Proteins/genetics/metabolism ; THP-1 Cells ; Lentivirus/genetics ; Recombinant Fusion Proteins/genetics ; Cysteine Endopeptidases/genetics/metabolism ; }, abstract = {The ubiquitin/proteasome system (UPS) plays a crucial role in maintaining cellular protein homeostasis. The catalytic activity of proteasome in the UPS is regulated by β1 (PSMB6), β2 (PSMB7), and β5 (PSMB5) subunits. Interferon (IFN)-γ, tumor necrosis factor (TNF)-α, inflammation, and oxidative stress can induce the replacement of β1, β2, and β5 with their respective immuno-subunits β1i (PSMB9), β2i (PSMB10), and β5i (PSMB8), which can be assembled into the immunoproteasome. Compared with the standard proteasome, the immunoproteasome exerts enhanced regulatory effects on immune responses, such as processing and presenting MHC class Ⅰ antigens, production of pro-inflammatory cytokines, and T cell differentiation and proliferation. Abnormal aggregation of immunoproteasomes can cause neurodegenerative diseases like Parkinson's disease, Alzheimer's disease, and amyotrophic lateral sclerosis. To explore the function of PSMB9 after bacterial infection, we constructed a lentivirus plasmid overexpressing PSMB9-eGFP-His and transfected the plasmid into HEK293T cells for packaging by using a triple-plasmid system in this study. After screening with puromycin, we obtained a stable human leukemia monocytic THP-1 cell line expressing the fusion protein of PSMB9. Western blotting (WB) and fluorescence microscopy verified the expression of the fusion protein in the stable THP-1 cells. Quantitative PCR (qPCR) was employed to measure the copies of PSMB9-eGFP in THP-1 cells. Immunofluorescence results found that eGFP-His did not affect the subcellular localization of PSMB9. The purification with nickel affinity chromatography confirmed that the fusion protein could be assembled into the 20S immunoproteasome and exhibited cleaving activity for fluorescent peptide substrates. These results indicated that the PSMB9-eGFP fusion gene was integrated into the chromosome, and could be stably expressed in the constructed THP-1 cell line. This cell line can be utilized for the research on subcellular localization, dynamic expression, and activity of PSMB9 in live cells at different infection conditions and disease stages. It also provides a model for the stable cell lines construction of other immunoproteasome subunits PSMB8 and PSMB10.}, } @article {pmid39044379, year = {2024}, author = {Goutman, SA and Goyal, NA and Payne, K and Paisán-Ruiz, C and Kupelian, V and Kang, ML and Mitchell, AA and Fecteau, TE}, title = {ALS Identified: two-year findings from a sponsored ALS genetic testing program.}, journal = {Annals of clinical and translational neurology}, volume = {11}, number = {8}, pages = {2201-2211}, pmid = {39044379}, issn = {2328-9503}, support = {//Biogen (Cambridge, MA, USA)/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/diagnosis ; Male ; *Genetic Testing ; Female ; Middle Aged ; Aged ; Adult ; United States ; }, abstract = {OBJECTIVE: To report initial results from the Amyotrophic Lateral Sclerosis (ALS) Identified genetic testing (GT) program on characteristics of individuals tested and frequency of reported disease-causing variants.

METHODS: ALS Identified used the Invitae Amyotrophic Lateral Sclerosis panel (Invitae, San Francisco, CA, USA) to assay 22 ALS-associated genes. Sponsored by Biogen (Cambridge, MA, USA), the program was launched in June 2021 and was available at no charge to individuals ≥18 years in the United States and Puerto Rico with an ALS diagnosis or a known family history of ALS. Deidentified data were available to Biogen.

RESULTS: As of 26 October 2023, 998 healthcare professionals ordered the panel at 681 unique care sites. Of 8054 individuals examined, 7483 (92.9%) were reported to have a clinical diagnosis of ALS, while 571 (7.1%) were asymptomatic relatives. Of the individuals with a clinical ALS diagnosis, 57.7% were male (n = 4319) and 42.3% female (n = 3164). Mean (SD) age at diagnosis is 62 (13) years. Out of the 7483 clinically diagnosed individuals, 1810 (24.2%) showed genetic variations in ALS-associated genes. Among these, 865 individuals (47.8%) carried pathogenic variants, and 44 (2.4%) had likely pathogenic variants, totaling 12.1% of the clinically diagnosed population.

INTERPRETATION: Since 2021 there has been robust uptake and sustained use of the ALS Identified program, one of the largest samples of people with ALS to date across the United States, demonstrating the interest and need for genetic ALS testing.}, } @article {pmid39044305, year = {2024}, author = {Chen, HH and Yeo, HT and Huang, YH and Tsai, LK and Lai, HJ and Tsao, YP and Chen, SL}, title = {AAV-NRIP gene therapy ameliorates motor neuron degeneration and muscle atrophy in ALS model mice.}, journal = {Skeletal muscle}, volume = {14}, number = {1}, pages = {17}, pmid = {39044305}, issn = {2044-5040}, support = {NSTC 112-2320-B-002-004//National Science and Technology Council/ ; NSTC 112-2320-B-002-004//National Science and Technology Council/ ; 10R891903//National Taiwan University/ ; }, mesh = {Animals ; *Amyotrophic Lateral Sclerosis/genetics/therapy/metabolism/pathology ; *Genetic Therapy/methods ; *Muscular Atrophy/genetics/therapy/metabolism/pathology ; *Disease Models, Animal ; *Motor Neurons/metabolism/pathology ; *Mice, Transgenic ; *Dependovirus/genetics ; Mice ; Humans ; Muscle, Skeletal/metabolism/pathology ; Neuromuscular Junction/metabolism/pathology ; Genetic Vectors/administration & dosage ; Nerve Degeneration/genetics/therapy ; Male ; Superoxide Dismutase-1/genetics/metabolism ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is characterized by progressive motor neuron (MN) degeneration, leading to neuromuscular junction (NMJ) dismantling and severe muscle atrophy. The nuclear receptor interaction protein (NRIP) functions as a multifunctional protein. It directly interacts with calmodulin or α-actinin 2, serving as a calcium sensor for muscle contraction and maintaining sarcomere integrity. Additionally, NRIP binds with the acetylcholine receptor (AChR) for NMJ stabilization. Loss of NRIP in muscles results in progressive motor neuron degeneration with abnormal NMJ architecture, resembling ALS phenotypes. Therefore, we hypothesize that NRIP could be a therapeutic factor for ALS.

METHODS: We used SOD1 G93A mice, expressing human SOD1 with the ALS-linked G93A mutation, as an ALS model. An adeno-associated virus vector encoding the human NRIP gene (AAV-NRIP) was generated and injected into the muscles of SOD1 G93A mice at 60 days of age, before disease onset. Pathological and behavioral changes were measured to evaluate the therapeutic effects of AAV-NRIP on the disease progression of SOD1 G93A mice.

RESULTS: SOD1 G93A mice exhibited lower NRIP expression than wild-type mice in both the spinal cord and skeletal muscle tissues. Forced NRIP expression through AAV-NRIP intramuscular injection was observed in skeletal muscles and retrogradely transduced into the spinal cord. AAV-NRIP gene therapy enhanced movement distance and rearing frequencies in SOD1 G93A mice. Moreover, AAV-NRIP increased myofiber size and slow myosin expression, ameliorated NMJ degeneration and axon terminal denervation at NMJ, and increased the number of α-motor neurons (α-MNs) and compound muscle action potential (CMAP) in SOD1 G93A mice.

CONCLUSIONS: AAV-NRIP gene therapy ameliorates muscle atrophy, motor neuron degeneration, and axon terminal denervation at NMJ, leading to increased NMJ transmission and improved motor functions in SOD1 G93A mice. Collectively, AAV-NRIP could be a potential therapeutic drug for ALS.}, } @article {pmid39042810, year = {2024}, author = {Haridevamuthu, B and Sathishkumar, K}, title = {Comment on Tsioti et al's "Systemic Lipopolysaccharide Exposure Exacerbates Choroidal Neovascularization in Mice".}, journal = {Ocular immunology and inflammation}, volume = {32}, number = {10}, pages = {2614-2615}, doi = {10.1080/09273948.2024.2377732}, pmid = {39042810}, issn = {1744-5078}, mesh = {*Choroidal Neovascularization/drug therapy ; Animals ; *Lipopolysaccharides ; Mice ; *Disease Models, Animal ; Macrophages/drug effects ; Fluorescein Angiography ; }, abstract = {The study "Systemic Lipopolysaccharide Exposure Exacerbates Choroidal Neovascularization in Mice" by Tsioti et al. explores the impact of systemic lipopolysaccharide (LPS) on choroidal neovascularization (CNV) progression. The findings reveal systemic LPS exposure significantly enhances fluorescein leakage, driven by increased pro-inflammatory monocyte-derived macrophages and microglia activation. The study underscores the importance of managing systemic inflammation to mitigate CNV progression, suggesting potential therapeutic strategies targeting CSF1R inhibition and Müller cell modulation. Future research should focus on elucidating the molecular pathways involved in LPS-induced CNV exacerbation and translating these findings into clinical interventions.}, } @article {pmid39042693, year = {2024}, author = {Celona, B and Salomonsson, SE and Wu, H and Dang, B and Kratochvil, HT and Clelland, CD and DeGrado, WF and Black, BL}, title = {Zfp106 binds to G-quadruplex RNAs and inhibits RAN translation and formation of RNA foci caused by G4C2 repeats.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {121}, number = {31}, pages = {e2220020121}, pmid = {39042693}, issn = {1091-6490}, support = {U01NS134062//HHS | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; HL146366//HHS | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; GM122603//HHS | NIH | National Institute of General Medical Sciences (NIGMS)/ ; K08 NS112330/NS/NINDS NIH HHS/United States ; U19 NS132303/NS/NINDS NIH HHS/United States ; R01 DK119621/DK/NIDDK NIH HHS/United States ; DK119621//HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)/ ; NS126499//HHS | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; R35 GM122603/GM/NIGMS NIH HHS/United States ; R01 NS126499/NS/NINDS NIH HHS/United States ; U01 NS134062/NS/NINDS NIH HHS/United States ; P01 HL146366/HL/NHLBI NIH HHS/United States ; AL210129//U.S. Department of Defense (DOD)/ ; U19NS132303//HHS | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; K99 GM138753/GM/NIGMS NIH HHS/United States ; K99GM138753//HHS | National Institutes of Health (NIH)/ ; }, mesh = {Animals ; Humans ; Mice ; *Amyotrophic Lateral Sclerosis/genetics/metabolism ; *C9orf72 Protein/genetics/metabolism ; DNA Repeat Expansion ; Frontotemporal Dementia/genetics/metabolism ; *G-Quadruplexes ; Nerve Tissue Proteins/metabolism/genetics ; Protein Binding ; Protein Biosynthesis ; *RNA/metabolism/genetics ; *RNA-Binding Proteins/metabolism/genetics ; }, abstract = {Expansion of intronic GGGGCC repeats in the C9orf72 gene causes amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. Transcription of the expanded repeats results in the formation of RNA-containing nuclear foci and altered RNA metabolism. In addition, repeat-associated non-AUG (RAN) translation of the expanded GGGGCC-repeat sequence results in the production of highly toxic dipeptide-repeat (DPR) proteins. GGGGCC repeat-containing transcripts form G-quadruplexes, which are associated with formation of RNA foci and RAN translation. Zfp106, an RNA-binding protein essential for motor neuron survival in mice, suppresses neurotoxicity in a Drosophila model of C9orf72 ALS. Here, we show that Zfp106 inhibits formation of RNA foci and significantly reduces RAN translation caused by GGGGCC repeats in cultured mammalian cells, and we demonstrate that Zfp106 coexpression reduces the levels of DPRs in C9orf72 patient-derived cells. Further, we show that Zfp106 binds to RNA G-quadruplexes and causes a conformational change in the G-quadruplex structure formed by GGGGCC repeats. Together, these data demonstrate that Zfp106 suppresses the formation of RNA foci and DPRs caused by GGGGCC repeats and suggest that the G-quadruplex RNA-binding function of Zfp106 contributes to its suppression of GGGGCC repeat-mediated cytotoxicity.}, } @article {pmid39039445, year = {2024}, author = {Jonsdottir, G and Haraldsdottir, E and Vilhjalmsson, R and Sigurdardottir, V and Hjaltason, H and Klinke, ME and Tryggvadottir, GB and Jonsdottir, H}, title = {Transition to end-of-life care in patients with neurological diseases in an acute hospital ward.}, journal = {BMC neurology}, volume = {24}, number = {1}, pages = {253}, pmid = {39039445}, issn = {1471-2377}, support = {71545//The Icelandic Nurses´ Association/ ; }, mesh = {Humans ; Male ; *Terminal Care/methods/statistics & numerical data ; Female ; Aged ; Middle Aged ; Retrospective Studies ; *Nervous System Diseases/therapy/diagnosis/epidemiology ; Aged, 80 and over ; Amyotrophic Lateral Sclerosis/therapy/diagnosis/mortality ; }, abstract = {BACKGROUND: Transitioning to end-of-life care and thereby changing the focus of treatment directives from life-sustaining treatment to comfort care is important for neurological patients in advanced stages. Late transition to end-of-life care for neurological patients has been described previously.

OBJECTIVE: To investigate whether previous treatment directives, primary medical diagnoses, and demographic factors predict the transition to end-of-life care and time to eventual death in patients with neurological diseases in an acute hospital setting.

METHOD: All consecutive health records of patients diagnosed with stroke, amyotrophic lateral sclerosis (ALS), and Parkinson's disease or other extrapyramidal diseases (PDoed), who died in an acute neurological ward between January 2011 and August 2020 were retrieved retrospectively. Descriptive statistics and multivariate Cox regression were used to examine the timing of treatment directives and death in relation to medical diagnosis, age, gender, and marital status.

RESULTS: A total of 271 records were involved in the analysis. Patients in all diagnostic categories had a treatment directive for end-of-life care, with patients with haemorrhagic stroke having the highest (92%) and patients with PDoed the lowest (73%) proportion. Cox regression identified that the likelihood of end-of-life care decision-making was related to advancing age (HR = 1.02, 95% CI: 1.007-1.039, P = 0.005), ischaemic stroke (HR = 1.64, 95% CI: 1.034-2.618, P = 0.036) and haemorrhagic stroke (HR = 2.04, 95% CI: 1.219-3.423, P = 0.007) diagnoses. End-of-life care decision occurred from four to twenty-two days after hospital admission. The time from end-of-life care decision to death was a median of two days. Treatment directives, demographic factors, and diagnostic categories did not increase the likelihood of death following an end-of-life care decision.

CONCLUSIONS: Results show not only that neurological patients transit late to end-of-life care but that the timeframe of the decision differs between patients with acute neurological diseases and those with progressive neurological diseases, highlighting the particular significance of the short timeframe of patients with the progressive neurological diseases ALS and PDoed. Different trajectories of patients with neurological diseases at end-of-life should be further explored and clinical guidelines expanded to embrace the high diversity in neurological patients.}, } @article {pmid39039135, year = {2024}, author = {Tahir, M and Yude, B and Mehmood, T and Bashir, S and Zhenping, Y and Awais, M}, title = {Classification of LAMOST spectra of B-type and hot subdwarf stars using kernel support vector machine.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {16815}, pmid = {39039135}, issn = {2045-2322}, abstract = {Machine learning has emerged as a leading field in artificial intelligence, demonstrating expert-level performance in various domains. Astronomy has benefited from machine learning techniques, particularly in classifying and identifying stars based on their features. This study focuses on the spectra-based classification of 11,408 B-type and 2422 hot subdwarf stars. The study employs baseline correction using Asymmetric Least Squares (ALS) to enhance classification accuracy. It applies the Pan-Core concept to identify 500 unique patterns or ranges for both types of stars. These patterns are the foundation for creating Support Vector Machine (SVM) models, including the linear (L-SVM), polynomial (P-SVM), and radial basis (R-SVM) kernels. Parameter tuning for the SVM models is achieved through cross-validation. Evaluation of the SVM models on test data reveals that the linear kernel SVM achieves the highest accuracy (87.0%), surpassing the polynomial kernel SVM (84.1%) and radial kernel SVM (80.1%). The average calibrated accuracy falls within the range of 90-95%. These results demonstrate the potential of using spectrum-based classification to aid astronomers in improving and expanding their understanding of stars, with a specific focus on the identification of hot subdwarf stars. This study presents a valuable investigation for astronomers, as it enables the classification of stars based on their spectra, leveraging machine learning techniques to enhance their knowledge and insights in astronomy.}, } @article {pmid39039102, year = {2024}, author = {Acien, A and Calcagno, N and Burke, KM and Mondesire-Crump, I and Holmes, AA and Mruthik, S and Goldy, B and Syrotenko, JE and Scheier, Z and Iyer, A and Clark, A and Keegan, M and Ushirogawa, Y and Kato, A and Yasuda, T and Lahav, A and Iwasaki, S and Pascarella, M and Johnson, SA and Arroyo-Gallego, T and Berry, JD}, title = {A novel digital tool for detection and monitoring of amyotrophic lateral sclerosis motor impairment and progression via keystroke dynamics.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {16851}, pmid = {39039102}, issn = {2045-2322}, mesh = {*Amyotrophic Lateral Sclerosis/diagnosis/physiopathology ; Humans ; *Disease Progression ; Female ; Male ; Middle Aged ; Aged ; *Smartphone ; Machine Learning ; Case-Control Studies ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a debilitating neurodegenerative condition leading to progressive muscle weakness, atrophy, and ultimately death. Traditional ALS clinical evaluations often depend on subjective metrics, making accurate disease detection and monitoring disease trajectory challenging. To address these limitations, we developed the nQiALS toolkit, a machine learning-powered system that leverages smartphone typing dynamics to detect and track motor impairment in people with ALS. The study included 63 ALS patients and 30 age- and sex-matched healthy controls. We introduce the three core components of this toolkit: the nQiALS-Detection, which differentiated ALS from healthy typing patterns with an AUC of 0.89; the nQiALS-Progression, which separated slow and fast progression at specific thresholds with AUCs ranging between 0.65 and 0.8; and the nQiALS-Fine Motor, which identified subtle progression in fine motor dysfunction, suggesting earlier prediction than the state-of-the-art assessment. Together, these tools represent an innovative approach to ALS assessment, offering a complementary, objective metric to traditional clinical methods and which may reshape our understanding and monitoring of ALS progression.}, } @article {pmid39038319, year = {2024}, author = {Zhao, T and Huang, J and Chi, W}, title = {The Diagnostic Advantages of MRI in Cerebral Infarction: Multi-Sequence Imaging and Improved Sensitivity in Early Detection.}, journal = {Alternative therapies in health and medicine}, volume = {}, number = {}, pages = {}, pmid = {39038319}, issn = {1078-6791}, abstract = {OBJECTIVE: The study aimed to investigate the diagnostic value of computed tomography (CT) and magnetic resonance imaging (MRI) in cerebral infarction (CI) in cerebrovascular diseases.

METHOD: 100 patients with acute ischemic cerebral infarction (AICI) were divided into a CT group and an MRI group. The diagnostic efficacy of the two diagnostic methods for CI was compared and analyzed.

RESULTS: Only 6 patients with acute early stage (AES) CI and 30 patients with acute late stage (ALS) CI were detected by CT, which was significantly less than those detected by MRI (P < .05); 5 patients with <5 mm infarction were detected by CT in ALS and 10 patients with 5-15 mm infarction were detected by CT in ALS, which were significantly less than those detected by MRI (P < .05); 3 patients were diagnosed with cerebral sulcus, fissure, and shallow and disappeared brain cistern, 4 patients with local gyrus swelling, and 31 patients with significant swelling by CT examination, which was significantly less than those detected by MRI (P < .05); the infarct area ratio measured by CT/ diffusion weighted imaging (DWI) was significantly lower than that measured by fluid attenuated inversion recovery (FLAIR)/DWI (P < .05); the diagnostic specificity (Sp), sensitivity (Se), Youden index, positive predictive value (PV), and negative PV of MRI were 0.82, 0.79, 0.58, 0.7, and 0.88, respectively, which were significantly better than those of CT (P < .05).

CONCLUSION: CT is not a sensitive technique for the diagnosis of early CI. Compared to CT, MRI has the characteristics of multi-sequence and multi-parameter imaging, is more sensitive to infarction within 2 hours after onset, and can more clearly and accurately diagnose CI.}, } @article {pmid39037980, year = {2024}, author = {Souza, AA and da Silva, ST and Macedo, LRD and Aires, DN and Pondofe, KM and Melo, LP and Valentim, RAM and Ribeiro, TS}, title = {Physical therapy for muscle strengthening in individuals with amyotrophic lateral sclerosis: A protocol for a systematic review and meta-analysis.}, journal = {PloS one}, volume = {19}, number = {7}, pages = {e0307470}, pmid = {39037980}, issn = {1932-6203}, mesh = {*Amyotrophic Lateral Sclerosis/therapy ; Humans ; *Muscle Strength ; *Systematic Reviews as Topic ; *Meta-Analysis as Topic ; Physical Therapy Modalities ; Female ; Male ; }, abstract = {INTRODUCTION: People with Amyotrophic Lateral Sclerosis (ALS) can present initially muscle weakness, which is a debilitating symptom that may be improved by engaging in muscle strengthening activities. Currently, the effects of motor interventions for muscle strengthening in people with ALS are unclear. This review intends to analyze the effects of motor interventions for muscle strengthening in individuals with ALS.

METHODS AND ANALYSIS: Randomized, non-randomized, and quasi-experimental clinical trials assessing individuals with ALS of both sexes, aged 18 years or older, who have received motor interventions for muscle strengthening considering all practices that can lead to increased strength, endurance, power and muscular hypertrophy will be included. No restriction on language, location, or publication date will be applied. MEDLINE, EMBASE, Cochrane Library (CENTRAL), SPORTDiscus, and Physiotherapy Evidence Database (PEDro) databases will be searched. The US National Institutes of Health Ongoing, ClinicalTrials.gov, and the reference lists of included studies will also be searched. Two reviewers will independently screen titles and abstracts and extract data from included studies. The methodological quality of the included studies will be assessed by the PEDro scale and the certainty of the evidence by the GRADE approach. Disagreements will be resolved by a third researcher. Findings will be presented in text and table formats. A meta-analysis will compare the effects of motor interventions for muscle strengthening versus placebo or other interventions.}, } @article {pmid39037015, year = {2024}, author = {Timmins, HC and Thompson, AE and Kiernan, MC}, title = {Diagnostic criteria for amyotrophic lateral sclerosis.}, journal = {Current opinion in neurology}, volume = {37}, number = {5}, pages = {570-576}, doi = {10.1097/WCO.0000000000001302}, pmid = {39037015}, issn = {1473-6551}, mesh = {*Amyotrophic Lateral Sclerosis/diagnosis/genetics ; Humans ; *Biomarkers/analysis ; }, abstract = {PURPOSE OF REVIEW: The present review will discuss the evolution of diagnostic criteria for amyotrophic lateral sclerosis (ALS) and biomarker considerations.

RECENT FINDINGS: To address the limitations of existing ALS diagnostic criteria, a consortium of key stakeholders developed the Gold Coast consensus criteria (GCC). The GCC has similar or greater sensitivity compared with the revised El Escorial (rEEC) and Awaji criteria (AC), particularly for atypical phenotypes, maintained across disease duration, severity, and site of onset. In addition to improving diagnostic sensitivity, using the GCC in clinical trials may promote an increased enrolment of up to 50% of ALS patients who do not currently meet the full diagnostic eligibility requirements of the rEEC. Future inclusion of genetic biomarkers may mitigate some limitations of the GCC, to further improve diagnostic utility. In advance of such a process, validation of these biomarkers will be required before inclusion as additional criteria.

SUMMARY: The GCC are simpler to use than previous consensus criteria, with demonstrated greater sensitivity and, enabling an earlier and more definitive ALS diagnosis, thereby facilitating wider enrolment into clinical trials. Broader implementation of the GCC in clinical trial settings is currently underway, globally.}, } @article {pmid39033904, year = {2024}, author = {Lu, XY and Li, MQ and Li, YT and Yao, JY and Zhang, LX and Zeng, ZH and Yu-Liu, and Chen, ZR and Li, CQ and Zhou, XF and Li, F}, title = {Oral edaravone ameliorates behavioral deficits and pathologies in a valproic acid-induced rat model of autism spectrum disorder.}, journal = {Neuropharmacology}, volume = {258}, number = {}, pages = {110089}, doi = {10.1016/j.neuropharm.2024.110089}, pmid = {39033904}, issn = {1873-7064}, mesh = {Animals ; *Valproic Acid/pharmacology/administration & dosage ; *Edaravone/pharmacology ; *Autism Spectrum Disorder/drug therapy/chemically induced ; *Disease Models, Animal ; Female ; *Oxidative Stress/drug effects ; Male ; Administration, Oral ; Pregnancy ; Rats ; Rats, Sprague-Dawley ; Brain/drug effects/metabolism/pathology ; Prenatal Exposure Delayed Effects/chemically induced ; Free Radical Scavengers/pharmacology/administration & dosage/therapeutic use ; Dose-Response Relationship, Drug ; Stereotyped Behavior/drug effects ; Behavior, Animal/drug effects ; Social Interaction/drug effects ; }, abstract = {Autism spectrum disorder (ASD) is neurodevelopmental disorder with a high incidence rate, characterized by social deficits and repetitive behaviors. There is currently no effective management available to treat the core symptoms of ASD; however, oxidative stress has been implicated in its pathogenesis. Edaravone (EDA), a free-radical scavenger, is used to treat amyotrophic lateral sclerosis (ALS) and acute ischemic stroke (AIS). Here, we hypothesized that an oral formula of EDA may have therapeutic efficacy in the treatment of core ASD symptoms. A rat model of autism was established by prenatal exposure to valproic acid (VPA), and the offsprings were orally treated with EDA at low (3 mg/kg), medium (10 mg/kg), and high (30 mg/kg) doses once daily for 28 days starting from postnatal day 25 (PND25). Oral EDA administration alleviated the core symptoms in VPA rats in a dose-dependent manner, including repetitive stereotypical behaviors and impaired social interaction. Furthermore, oral administration of EDA significantly reduced oxidative stress in a dose-dependent manner, as evidenced by a reduction in oxidative stress markers and an increase in antioxidants in the blood and brain. In addition, oral EDA significantly attenuated downstream pathologies, including synaptic and mitochondrial damage in the brain. Proteomic analysis further revealed that EDA corrected the imbalance in brain oxidative reduction and mitochondrial proteins induced by prenatal VPA administration. Overall, these findings demonstrate that oral EDA has therapeutic potential for ASD by targeting the oxidative stress pathway of disease pathogenesis and paves the way towards clinical studies.}, } @article {pmid39032803, year = {2024}, author = {He, Q and Zhou, Y and Jin, J and Tian, Q and Li, H and Hou, B and Xie, A}, title = {Association between NEK1 gene polymorphisms and the potential risk of sporadic Parkinson's disease in the Chinese Northern Han population: A case-control study.}, journal = {Neuroscience letters}, volume = {837}, number = {}, pages = {137913}, doi = {10.1016/j.neulet.2024.137913}, pmid = {39032803}, issn = {1872-7972}, mesh = {Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Case-Control Studies ; China/epidemiology ; East Asian People/genetics ; Genetic Association Studies ; *Genetic Predisposition to Disease ; Genotype ; *NIMA-Related Kinase 1/genetics ; *Parkinson Disease/genetics ; *Polymorphism, Single Nucleotide ; }, abstract = {OBJECTIVE: Parkinson's disease (PD) has been identified as a genetically influenced disease linked to various genetic loci. Previous studies have suggested that neurodegenerative illnesses, including PD, Alzheimer's disease, and Amyotrophic lateral sclerosis (ALS), may share certain genetic loci. Recently, the NEK1 gene was identified as overlapping between PD and ALS. We therefore wanted to explore the potential association between the NEK1 gene single nucleotide polymorphisms (SNPs) and the clinical features and pathophysiology of sporadic PD in a northern Chinese population.

METHODS: A total of 510 sporadic PD patients and 510 age- and sex-matched healthy controls (HCs) were included in this study. Two SNPs (rs4563461 and rs66509122) of the NEK1 gene were genotyped using polymerase chain reaction (PCR). And we analyzed the association between NEK1 gene polymorphisms and clinical manifestations.

RESULTS: Allele T (C vs. T, P = 0.018) and genotype TT (CC vs. TT: P = 0.021) of rs66509122 among PD group and HCs were significantly different. In addition, we discovered that the rs66509122 genotype TT was associated with depression in early-onset PD (EOPD) (P = 0.031) and diabetes in female PD (P = 0.032). Unfortunately, no distinct correlation of rs4563461 polymorphisms with sporadic PD susceptibility was found in either the overall group (C vs. T, P = 0.086) or other subgroups. However, the T allele of rs4563461 was significantly correlated with sleep disorders in the PD group, especially in the late-onset PD (LOPD) group and male PD group.

CONCLUSION: This study found that the NEK1 rs66509122 polymorphism was associated with a lower risk of sporadic PD, while T allele of rs66509122 may be a protective factor for PD. The NEK1 rs4563461 and rs66509122 polymorphisms both showed correlations with some non-motor symptoms in sporadic PD patients. Further research with a larger sample and varied ethnic groups is needed to investigate the role of NEK1 gene polymorphisms in the pathophysiology of PD.}, } @article {pmid39032788, year = {2024}, author = {Wu, KJ and Wei, KC}, title = {Response to Hasan et al's "Dupilumab therapy for atopic dermatitis is associated with increased risk of cutaneous T cell lymphoma: A retrospective cohort study".}, journal = {Journal of the American Academy of Dermatology}, volume = {91}, number = {5}, pages = {e145-e146}, doi = {10.1016/j.jaad.2024.06.091}, pmid = {39032788}, issn = {1097-6787}, } @article {pmid39031772, year = {2024}, author = {Meyer, T and Schumann, P and Weydt, P and Petri, S and Weishaupt, JH and Weyen, U and Koch, JC and Günther, R and Regensburger, M and Boentert, M and Wiesenfarth, M and Koc, Y and Kolzarek, F and Kettemann, D and Norden, J and Bernsen, S and Elmas, Z and Conrad, J and Valkadinov, I and Vidovic, M and Dorst, J and Ludolph, AC and Hesebeck-Brinckmann, J and Spittel, S and Münch, C and Maier, A and Körtvélyessy, P}, title = {Clinical and patient-reported outcomes and neurofilament response during tofersen treatment in SOD1-related ALS-A multicenter observational study over 18 months.}, journal = {Muscle & nerve}, volume = {70}, number = {3}, pages = {333-345}, doi = {10.1002/mus.28182}, pmid = {39031772}, issn = {1097-4598}, support = {(H4017703513237604)//Boris Canessa ALS Stiftung (Düsseldorf, Germany) and Martin Herrenknecht Fonds for ALS Research/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy/genetics ; Male ; Female ; *Patient Reported Outcome Measures ; Middle Aged ; Aged ; *Superoxide Dismutase-1/genetics ; *Neurofilament Proteins/blood ; Treatment Outcome ; Disease Progression ; Adult ; Oligonucleotides/therapeutic use ; }, abstract = {INTRODUCTION/AIMS: In amyotrophic lateral sclerosis (ALS) caused by SOD1 mutations (SOD1-ALS), tofersen received accelerated approval in the United States and is available via expanded access programs (EAP) outside the United States. This multicenter study investigates clinical and patient-reported outcomes (PRO) and serum neurofilament light chain (sNfL) during tofersen treatment in an EAP in Germany.

METHODS: Sixteen SOD1-ALS patients receiving tofersen for at least 6 months were analyzed. The ALS progression rate (ALS-PR), as measured by the monthly change of the ALS functional rating scale-revised (ALSFRS-R), slow vital capacity (SVC), and sNfL were investigated. PRO included the Measure Yourself Medical Outcome Profile (MYMOP2), Treatment Satisfaction Questionnaire for Medication (TSQM-9), and Net Promoter Score (NPS).

RESULTS: Mean tofersen treatment was 11 months (6-18 months). ALS-PR showed a mean change of -0.2 (range 0 to -1.1) and relative reduction by 25%. Seven patients demonstrated increased ALSFRS-R. SVC was stable (mean 88%, range -15% to +28%). sNfL decreased in all patients except one heterozygous D91A-SOD1 mutation carrier (mean change of sNfL -58%, range -91 to +27%, p < .01). MYMOP2 indicated improved symptom severity (n = 10) or yet perception of partial response (n = 6). TSQM-9 showed high global treatment satisfaction (mean 83, SD 16) although the convenience of drug administration was modest (mean 50, SD 27). NPS revealed a very high recommendation rate for tofersen (NPS +80).

DISCUSSION: Data from this EAP supported the clinical and sNfL response to tofersen in SOD1-ALS. PRO suggested a favorable patient perception of tofersen treatment in clinical practice.}, } @article {pmid39030740, year = {2024}, author = {Jonson, C and Levine, KS and Lake, J and Hertslet, L and Jones, L and Patel, D and Kim, J and Bandres-Ciga, S and Terry, N and Mata, IF and Blauwendraat, C and Singleton, AB and Nalls, MA and Yokoyama, JS and Leonard, HL}, title = {Assessing the lack of diversity in genetics research across neurodegenerative diseases: A systematic review of the GWAS Catalog and literature.}, journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association}, volume = {20}, number = {8}, pages = {5740-5756}, pmid = {39030740}, issn = {1552-5279}, support = {U19AG079774/NS/NINDS NIH HHS/United States ; R01 AG062588/AG/NIA NIH HHS/United States ; ZO1AG000534/HH/HHS/United States ; U19 AG079774/AG/NIA NIH HHS/United States ; P30 AG062422/AG/NIA NIH HHS/United States ; P01 AG019724/AG/NIA NIH HHS/United States ; R01 AG057234/AG/NIA NIH HHS/United States ; 75N95022C00031/NS/NINDS NIH HHS/United States ; //Intramural Research Program/ ; P01AG019724/NS/NINDS NIH HHS/United States ; P30AG062422/NS/NINDS NIH HHS/United States ; /ALZ/Alzheimer's Association/United States ; U54NS123985/NS/NINDS NIH HHS/United States ; 75N95022C00031/DA/NIDA NIH HHS/United States ; U54 NS123985/NS/NINDS NIH HHS/United States ; R01AG057234/NS/NINDS NIH HHS/United States ; R01AG062588/NS/NINDS NIH HHS/United States ; //Global Brain Health Institute; and the Mary Oakley Foundation/ ; //Rainwater Charitable Foundation/ ; }, mesh = {Humans ; Genetic Predisposition to Disease/genetics ; *Genome-Wide Association Study ; *Neurodegenerative Diseases/genetics ; White People/genetics ; }, abstract = {The under-representation of non-European cohorts in neurodegenerative disease genome-wide association studies (GWAS) hampers precision medicine efforts. Despite the inherent genetic and phenotypic diversity in these diseases, GWAS research consistently exhibits a disproportionate emphasis on participants of European ancestry. This study reviews GWAS up to 2022, focusing on non-European or multi-ancestry neurodegeneration studies. We conducted a systematic review of GWAS results and publications up to 2022, focusing on non-European or multi-ancestry neurodegeneration studies. Rigorous article inclusion and quality assessment methods were employed. Of 123 neurodegenerative disease (NDD) GWAS reviewed, 82% predominantly featured European ancestry participants. A single European study identified over 90 risk loci, compared to a total of 50 novel loci in identified in all non-European or multi-ancestry studies. Notably, only six of the loci have been replicated. The significant under-representation of non-European ancestries in NDD GWAS hinders comprehensive genetic understanding. Prioritizing genomic diversity in future research is crucial for advancing NDD therapies and understanding. HIGHLIGHTS: Eighty-two percent of neurodegenerative genome-wide association studies (GWAS) focus on Europeans. Only 6 of 50 novel neurodegenerative disease (NDD) genetic loci have been replicated. Lack of diversity significantly hampers understanding of NDDs. Increasing diversity in NDD genetic research is urgently required. New initiatives are aiming to enhance diversity in NDD research.}, } @article {pmid39030617, year = {2024}, author = {Chen, T and Dai, Y and Hu, C and Lin, Z and Wang, S and Yang, J and Zeng, L and Li, S and Li, W}, title = {Cellular and molecular mechanisms of the blood-brain barrier dysfunction in neurodegenerative diseases.}, journal = {Fluids and barriers of the CNS}, volume = {21}, number = {1}, pages = {60}, pmid = {39030617}, issn = {2045-8118}, support = {LGD21H250001 and LGD22H250001//Basic Public Welfare Research Program of Zhejiang Province/ ; LGD21H250001 and LGD22H250001//Basic Public Welfare Research Program of Zhejiang Province/ ; LGD21H250001 and LGD22H250001//Basic Public Welfare Research Program of Zhejiang Province/ ; LGD21H250001 and LGD22H250001//Basic Public Welfare Research Program of Zhejiang Province/ ; LGD21H250001 and LGD22H250001//Basic Public Welfare Research Program of Zhejiang Province/ ; LGD21H250001 and LGD22H250001//Basic Public Welfare Research Program of Zhejiang Province/ ; LGD21H250001 and LGD22H250001//Basic Public Welfare Research Program of Zhejiang Province/ ; LGD21H250001 and LGD22H250001//Basic Public Welfare Research Program of Zhejiang Province/ ; LGD21H250001 and LGD22H250001//Basic Public Welfare Research Program of Zhejiang Province/ ; No.X-202102//Scientific Research Foundation of Zhejiang University City College/ ; }, mesh = {*Blood-Brain Barrier/metabolism/physiopathology ; Humans ; *Neurodegenerative Diseases/metabolism/physiopathology ; Animals ; }, abstract = {BACKGROUND: Maintaining the structural and functional integrity of the blood-brain barrier (BBB) is vital for neuronal equilibrium and optimal brain function. Disruptions to BBB performance are implicated in the pathology of neurodegenerative diseases.

MAIN BODY: Early indicators of multiple neurodegenerative disorders in humans and animal models include impaired BBB stability, regional cerebral blood flow shortfalls, and vascular inflammation associated with BBB dysfunction. Understanding the cellular and molecular mechanisms of BBB dysfunction in brain disorders is crucial for elucidating the sustenance of neural computations under pathological conditions and for developing treatments for these diseases. This paper initially explores the cellular and molecular definition of the BBB, along with the signaling pathways regulating BBB stability, cerebral blood flow, and vascular inflammation. Subsequently, we review current insights into BBB dynamics in Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and multiple sclerosis. The paper concludes by proposing a unified mechanism whereby BBB dysfunction contributes to neurodegenerative disorders, highlights potential BBB-focused therapeutic strategies and targets, and outlines lessons learned and future research directions.

CONCLUSIONS: BBB breakdown significantly impacts the development and progression of neurodegenerative diseases, and unraveling the cellular and molecular mechanisms underlying BBB dysfunction is vital to elucidate how neural computations are sustained under pathological conditions and to devise therapeutic approaches.}, } @article {pmid39030200, year = {2024}, author = {Erb, ML and Sipple, K and Levine, N and Chen, X and Moore, DJ}, title = {Adult-onset deletion of ATP13A2 in mice induces progressive nigrostriatal pathway dopaminergic degeneration and lysosomal abnormalities.}, journal = {NPJ Parkinson's disease}, volume = {10}, number = {1}, pages = {133}, pmid = {39030200}, issn = {2373-8057}, support = {PF-FBS-1894//Parkinson's Foundation (Parkinson's Foundation, Inc.)/ ; PF-FBS-1894//Parkinson's Foundation (Parkinson's Foundation, Inc.)/ ; }, abstract = {Although most cases of Parkinson's disease (PD) are sporadic, mutations in over 20 genes are known to cause heritable forms of the disease. Recessive loss-of-function mutations in ATP13A2, a lysosomal transmembrane P5B-type ATPase and polyamine exporter, can cause early-onset familial PD. Familial ATP13A2 mutations are also linked to related neurodegenerative diseases, including Kufor-Rakeb syndrome, hereditary spastic paraplegias, neuronal ceroid lipofuscinosis, and amyotrophic lateral sclerosis. Despite the severe effects of ATP13A2 mutations in humans, ATP13A2 knockout (KO) mice fail to exhibit neurodegeneration even at advanced ages, making it challenging to study the neuropathological effects of ATP13A2 loss in vivo. Germline deletion of ATP13A2 in rodents may trigger the upregulation of compensatory pathways during embryonic development that mask the full neurotoxic effects of ATP13A2 loss in the brain. To explore this idea, we selectively deleted ATP13A2 in the adult mouse brain by the unilateral delivery of an AAV-Cre vector into the substantia nigra of young adult mice carrying conditional loxP-flanked ATP13A2 KO alleles. We observe a progressive loss of striatal dopaminergic nerve terminals at 3 and 10 months after AAV-Cre delivery. Cre-injected mice also exhibit robust dopaminergic neuronal degeneration in the substantia nigra at 10 months. Adult-onset ATP13A2 KO also recreates many of the phenotypes observed in aged germline ATP13A2 KO mice, including lysosomal abnormalities, p62-positive inclusions, and neuroinflammation. Our study demonstrates that the adult-onset homozygous deletion of ATP13A2 in the nigrostriatal pathway produces robust and progressive dopaminergic neurodegeneration that serves as a useful in vivo model of ATP13A2-related neurodegenerative diseases.}, } @article {pmid39030186, year = {2024}, author = {Dubbioso, R and Spisto, M and Verde, L and Iuzzolino, VV and Senerchia, G and Salvatore, E and De Pietro, G and De Falco, I and Sannino, G}, title = {Voice signals database of ALS patients with different dysarthria severity and healthy controls.}, journal = {Scientific data}, volume = {11}, number = {1}, pages = {800}, pmid = {39030186}, issn = {2052-4463}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology/complications ; *Dysarthria/physiopathology ; Male ; Female ; Voice ; Databases, Factual ; Middle Aged ; Adult ; Aged ; Case-Control Studies ; }, abstract = {This paper describes a new publicly-available database of VOiCe signals acquired in Amyotrophic Lateral Sclerosis (ALS) patients (VOC-ALS) and healthy controls performing different speech tasks. This dataset consists of 1224 voice signals recorded from 153 participants: 51 healthy controls (32 males and 19 females) and 102 ALS patients (65 males and 37 females) with different severity of dysarthria. Each subject's voice was recorded using a smartphone application (Vox4Health) while performing several vocal tasks, including a sustained phonation of the vowels /a/, /e/, /i/, /o/, /u/ and /pa/, /ta/, /ka/ syllable repetition. Basic derived speech metrics such as harmonics-to-noise ratio, mean and standard deviation of fundamental frequency (F0), jitter and shimmer were calculated. The F0 standard deviation of vowels and syllables showed an excellent ability to identify people with ALS and to discriminate the different severity of dysarthria. These data represent the most comprehensive database of voice signals in ALS and form a solid basis for research on the recognition of voice impairment in ALS patients for use in clinical applications.}, } @article {pmid39030042, year = {2024}, author = {Haberkamp, M and Aislaitner, G and Martínez-Lapiscina, EH and Weise, M}, title = {Tofersen for SOD-1-associated amyotrophic lateral sclerosis.}, journal = {The Lancet. Neurology}, volume = {23}, number = {8}, pages = {772-773}, doi = {10.1016/S1474-4422(24)00259-X}, pmid = {39030042}, issn = {1474-4465}, mesh = {*Amyotrophic Lateral Sclerosis/genetics ; Humans ; *Superoxide Dismutase-1/genetics ; }, } @article {pmid39029959, year = {2024}, author = {}, title = {Erratum: Garbuzova-Davis et al., "Apolipoprotein A1 Enhances Endothelial Cell Survival in an In Vitro Model of ALS".}, journal = {eNeuro}, volume = {11}, number = {7}, pages = {}, doi = {10.1523/ENEURO.0280-24.2024}, pmid = {39029959}, issn = {2373-2822}, } @article {pmid39028002, year = {2025}, author = {Mercadante, S and Petronaci, A and Terranova, A and Casuccio, A}, title = {Characteristics of Patients With Amyotrophic Lateral Sclerosis Followed by a Home Palliative Care Team.}, journal = {The American journal of hospice & palliative care}, volume = {42}, number = {5}, pages = {483-488}, doi = {10.1177/10499091241266985}, pmid = {39028002}, issn = {1938-2715}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy/psychology ; Male ; *Palliative Care/organization & administration/statistics & numerical data ; Female ; *Home Care Services/organization & administration ; Middle Aged ; Aged ; *Patient Care Team/organization & administration ; Respiration, Artificial/statistics & numerical data ; Advance Directives/statistics & numerical data ; Nutritional Support ; Aged, 80 and over ; Referral and Consultation ; Adult ; Noninvasive Ventilation/statistics & numerical data ; Patient Care Planning/organization & administration ; }, abstract = {BackgroundInformation about patients with amyothrophic lateral sclerosis (ALS) followed at home is limited.ObjectivesTo assess patients's characteristics at admission to a home palliative care program based on a multidisciplinary team, and the temporal course along the trajectory of ALS disease.DesignRetrospective. Setting/subjects: Charts of a consecutive number of ALS patients who were referred to a specialistic home palliative care were reviewed.MeasurementGeneral data, referral, start of home palliative care, use of ventilator support and nutritional support, were recorded. The existence of advance directives and shared care planning was also collected.Results82 patients were examined; 31 patients died before the term of the study and 51 patients were still living. No patient anticipately expressed their will regarding their treatments. However, a certain number of patients shared a care planning with ALS team, generally after starting home care. Most patients did not have ventilatory support at the beginning of home care assistance, but progressively received ventilatory support by NIV or MV, particularly those who were still living. NIV at start of home care was negatively correlated to frontotemporal dementia. (P = 0.015), and directly correlated to referral from hospital and GP (P = 0.031) and awareness of disease (P = 0.034). Gastrostomy at start of home care was positively correlated to referral from hospital (P = 0.046). Gastrostomy during home care was correlated to bulbar SLA (P = 0.017). The use of NIV during home care was positively correlated to shared care planning (P = 0.001).ConclusionThe continuous presence of a multi-specialist team may provide timely intervention, guarantee and trust on the part of the patient and family members.}, } @article {pmid39026758, year = {2025}, author = {Onwunma, J and Binsabaan, S and Allen, SP and Sankaran, B and Wohlever, ML}, title = {ALS mutations disrupt self-association between the Ubiquilin Sti1 hydrophobic groove and internal placeholder sequences.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {39026758}, issn = {2692-8205}, support = {P30 GM124169/GM/NIGMS NIH HHS/United States ; R35 GM137904/GM/NIGMS NIH HHS/United States ; }, abstract = {Ubiquilins are molecular chaperones that play multifaceted roles in proteostasis, with point mutations in UBQLN2 leading to altered phase separation properties and Amyotrophic Lateral Sclerosis (ALS). Our mechanistic understanding of this essential process has been hindered by a lack of structural information on the Sti1 domain, which is essential for Ubiquilin chaperone activity and phase separation. Here, we present the first crystal structure of a Ubiquilin family Sti1 domain bound to a transmembrane domain (TMD) and show that ALS mutations disrupt the Sti1-TMD interaction. We then demonstrate that Ubiquilins contain multiple conserved, internal sequences that bind to the Sti1 domain, including the PXX region which is a hotspot for ALS mutations. We propose that these placeholder sequences prevent solvent exposure of the Sti1 hydrophobic groove and contribute to the multivalency that drives Ubiquilin phase separation. Together, this work provides a new paradigm for understanding how Sti1 domains modulate Ubiquilin chaperone activity and phase separation and offer insights into the molecular basis of ALS pathogenesis.}, } @article {pmid39026010, year = {2024}, author = {Read, TA and Cisterna, BA and Skruber, K and Ahmadieh, S and Liu, TM and Vitriol, JA and Shi, Y and Black, JB and Butler, MT and Lindamood, HL and Lefebvre, AE and Cherezova, A and Ilatovskaya, DV and Bear, JE and Weintraub, NL and Vitriol, EA}, title = {The actin binding protein profilin 1 localizes inside mitochondria and is critical for their function.}, journal = {EMBO reports}, volume = {25}, number = {8}, pages = {3240-3262}, pmid = {39026010}, issn = {1469-3178}, support = {R35 GM130312/GM/NIGMS NIH HHS/United States ; R35 GM137959/GM/NIGMS NIH HHS/United States ; R35GM137959//Foundation for the National Institutes of Health (FNIH)/ ; }, mesh = {*Profilins/metabolism/genetics ; *Mitochondria/metabolism/genetics ; Humans ; *Actins/metabolism ; Mitophagy/genetics ; Lysosomes/metabolism ; Cytosol/metabolism ; Gene Knockout Techniques ; Autophagosomes/metabolism ; HeLa Cells ; }, abstract = {The monomer-binding protein profilin 1 (PFN1) plays a crucial role in actin polymerization. However, mutations in PFN1 are also linked to hereditary amyotrophic lateral sclerosis, resulting in a broad range of cellular pathologies which cannot be explained by its primary function as a cytosolic actin assembly factor. This implies that there are important, undiscovered roles for PFN1 in cellular physiology. Here we screened knockout cells for novel phenotypes associated with PFN1 loss of function and discovered that mitophagy was significantly upregulated. Indeed, despite successful autophagosome formation, fusion with the lysosome, and activation of additional mitochondrial quality control pathways, PFN1 knockout cells accumulate depolarized, dysmorphic mitochondria with altered metabolic properties. Surprisingly, we also discovered that PFN1 is present inside mitochondria and provide evidence that mitochondrial defects associated with PFN1 loss are not caused by reduced actin polymerization in the cytosol. These findings suggest a previously unrecognized role for PFN1 in maintaining mitochondrial integrity and highlight new pathogenic mechanisms that can result from PFN1 dysregulation.}, } @article {pmid39025824, year = {2024}, author = {Lorenc, T and Khouja, C and Harden, M and Fulbright, H and Thomas, J}, title = {Defensive healthcare practice: systematic review of qualitative evidence.}, journal = {BMJ open}, volume = {14}, number = {7}, pages = {e085673}, pmid = {39025824}, issn = {2044-6055}, mesh = {Humans ; *Qualitative Research ; *Defensive Medicine ; Attitude of Health Personnel ; }, abstract = {OBJECTIVE: To synthesise qualitative evidence on clinicians' views and experiences of defensive practice.

DESIGN: Systematic review of qualitative data.

DATA SOURCES: MEDLINE, Embase, PsycINFO, AMED, Maternity and Infant Care, CINAHL, ASSIA, Sociological Abstracts, Proquest Dissertations & Theses and PROSPERO were searched from 2000 to October 2023.

ELIGIBILITY CRITERIA: We included English-language studies of clinicians which reported qualitative data on the impact of litigation or complaints on clinical practice.

DATA EXTRACTION AND SYNTHESIS: We coded findings data line by line using a grounded theory approach. We assessed quality using Hawker et al's tool and synthesised data thematically.

RESULTS: 17 studies were included. Participants identify a range of clinical decisions which may be defensively motivated, relating to diagnosis and documentation as well as to treatment. Defensive practice often relates to a diffuse sense of risk rather than the direct threat of litigation and may overlap with other motivations, such as perceived pressure from patients or the desire to avoid harm. Defensive practice is seen to be harmful in many ways, but again, these perceptions may gain force from broader narratives of mistrust and disempowerment, as much as from the risk of litigation.

CONCLUSIONS: The idea of defensive practice, as enacted, is more complex than some theoretical accounts suggest and may often function to express broader concerns about the work of clinical care. The qualitative evidence calls into question the view of defensive practice as a key mediator linking litigation risk to inappropriate treatment and excess costs.}, } @article {pmid39023312, year = {2024}, author = {Miceli, M and Cannariato, M and Tortarolo, R and Pallante, L and Zizzi, EA and Deriu, MA}, title = {Conformational Dynamics and Molecular Characterization of Alsin MORN Monomer and Dimeric Assemblies.}, journal = {Proteins}, volume = {92}, number = {11}, pages = {1343-1353}, doi = {10.1002/prot.26728}, pmid = {39023312}, issn = {1097-0134}, support = {GSP 20005_PAsIAHSP007//Fondazione Telethon/ ; //Associazione Help Olly Onlus-Italy/ ; }, mesh = {*Protein Multimerization ; Humans ; Molecular Dynamics Simulation ; Protein Conformation, alpha-Helical ; Protein Stability ; Protein Conformation, beta-Strand ; Protein Domains ; Amino Acid Sequence ; Models, Molecular ; Protein Interaction Domains and Motifs ; Protein Conformation ; Guanine Nucleotide Exchange Factors ; }, abstract = {Despite the ubiquity of membrane occupation recognition nexus (MORN) motifs across diverse species in both eukaryotic and prokaryotic organisms, these protein domains remain poorly characterized. Their significance is underscored in the context of the Alsin protein, implicated in the debilitating condition known as infantile-onset ascending hereditary spastic paralysis (IAHSP). Recent investigations have proposed that mutations within the Alsin MORN domain disrupt proper protein assembly, precluding the formation of the requisite tetrameric configuration essential for the protein's inherent biological activity. However, a comprehensive understanding of the relationship between the biological functions of Alsin and its three-dimensional molecular structure is hindered by the lack of available experimental structures. In this study, we employed and compared several protein structure prediction algorithms to identify a three-dimensional structure for the putative MORN of Alsin. Furthermore, inspired by experimental pieces of evidence from previous studies, we employed the developed models to predict and investigate two homo-dimeric assemblies, characterizing their stability. This study's insights into the three-dimensional structure of the Alsin MORN domain and the stability dynamics of its homo-dimeric assemblies suggest an antiparallel linear configuration stabilized by a noncovalent interaction network.}, } @article {pmid39023172, year = {2024}, author = {Zaky, MH and Shoorangiz, R and Poudel, GR and Yang, L and Innes, CRH and Jones, RD}, title = {Conscious but not thinking-Mind-blanks during visuomotor tracking: An fMRI study of endogenous attention lapses.}, journal = {Human brain mapping}, volume = {45}, number = {11}, pages = {e26781}, pmid = {39023172}, issn = {1097-0193}, support = {08-VDV-01 EHB//Marsden Fund, Royal Society of New Zealand/ ; //University of Canterbury/ ; //University of Otago/ ; 236930//Lottery Health Research/ ; }, mesh = {Humans ; Adult ; *Magnetic Resonance Imaging ; Female ; Male ; Young Adult ; *Attention/physiology ; *Psychomotor Performance/physiology ; Middle Aged ; Eye-Tracking Technology ; Thinking/physiology ; Nerve Net/diagnostic imaging/physiopathology/physiology ; Consciousness/physiology ; Visual Perception/physiology ; Motor Activity/physiology ; }, abstract = {Attention lapses (ALs) are complete lapses of responsiveness in which performance is briefly but completely disrupted and during which, as opposed to microsleeps, the eyes remain open. Although the phenomenon of ALs has been investigated by behavioural and physiological means, the underlying cause of an AL has largely remained elusive. This study aimed to investigate the underlying physiological substrates of behaviourally identified endogenous ALs during a continuous visuomotor task, primarily to answer the question: Were the ALs during this task due to extreme mind-wandering or mind-blanks? The data from two studies were combined, resulting in data from 40 healthy non-sleep-deprived subjects (20M/20F; mean age 27.1 years, 20-45). Only 17 of the 40 subjects were used in the analysis due to a need for a minimum of two ALs per subject. Subjects performed a random 2-D continuous visuomotor tracking task for 50 and 20 min in Studies 1 and 2, respectively. Tracking performance, eye-video, and functional magnetic resonance imaging (fMRI) were recorded simultaneously. A human expert visually inspected the tracking performance and eye-video recordings to identify and categorise lapses of responsiveness as microsleeps or ALs. Changes in neural activity during 85 ALs (17 subjects) relative to responsive tracking were estimated by whole-brain voxel-wise fMRI and by haemodynamic response (HR) analysis in regions of interest (ROIs) from seven key networks to reveal the neural signature of ALs. Changes in functional connectivity (FC) within and between the key ROIs were also estimated. Networks explored were the default mode network, dorsal attention network, frontoparietal network, sensorimotor network, salience network, visual network, and working memory network. Voxel-wise analysis revealed a significant increase in blood-oxygen-level-dependent activity in the overlapping dorsal anterior cingulate cortex and supplementary motor area region but no significant decreases in activity; the increased activity is considered to represent a recovery-of-responsiveness process following an AL. This increased activity was also seen in the HR of the corresponding ROI. Importantly, HR analysis revealed no trend of increased activity in the posterior cingulate of the default mode network, which has been repeatedly demonstrated to be a strong biomarker of mind-wandering. FC analysis showed decoupling of external attention, which supports the involuntary nature of ALs, in addition to the neural recovery processes. Other findings were a decrease in HR in the frontoparietal network before the onset of ALs, and a decrease in FC between default mode network and working memory network. These findings converge to our conclusion that the ALs observed during our task were involuntary mind-blanks. This is further supported behaviourally by the short duration of the ALs (mean 1.7 s), which is considered too brief to be instances of extreme mind-wandering. This is the first study to demonstrate that at least the majority of complete losses of responsiveness on a continuous visuomotor task are, if not due to microsleeps, due to involuntary mind-blanks.}, } @article {pmid39022351, year = {2024}, author = {Corvino, A and Caliendo, G and Fiorino, F and Frecentese, F and Valsecchi, V and Lombardi, G and Anzilotti, S and Andreozzi, G and Scognamiglio, A and Sparaco, R and Perissutti, E and Severino, B and Gargiulo, M and Santagada, V and Pignataro, G}, title = {Newly Synthesized Indolylacetic Derivatives Reduce Tumor Necrosis Factor-Mediated Neuroinflammation and Prolong Survival in Amyotrophic Lateral Sclerosis Mice.}, journal = {ACS pharmacology & translational science}, volume = {7}, number = {7}, pages = {1996-2005}, pmid = {39022351}, issn = {2575-9108}, abstract = {The debilitating neurodegenerative disease known as amyotrophic lateral sclerosis (ALS) is characterized by the progressive loss of motor neurons (MNs) in the brain, spinal cord, and motor cortex. The ALS neuroinflammatory component is being characterized and includes the overexpression of mediators, such as inducible nitric oxide synthase (iNOS) and tumor necrosis factor-α (TNF-α). Currently, there are no effective treatments for ALS. Indeed, riluzole, an N-methyl-D-aspartate (NMDA) glutamate receptor blocker, and edaravone, a reactive oxygen species (ROS) scavenger, are currently the sole two medications approved for ALS treatment. However, their efficacy in extending life expectancy typically amounts to only a few months. In order to improve the medicaments for the treatment of neurodegenerative diseases, preferably ALS, novel substituted 2-methyl-3-indolylacetic derivatives (compounds II-IV) were developed by combining the essential parts of two small molecules, namely, the opioids containing a 4-piperidinyl ring with indomethacin, previously shown to be efficacious in different experimental models of neuroinflammation. The synthesized compounds were evaluated for their potential capability of slowing down neurodegeneration associated with ALS progression in preclinical models of the disease in vitro and in vivo. Notably, we produced data to demonstrate that the treatment with the newly synthesized compound III: (1) prevented the upregulation of TNF-α observed in BV-2 microglial cells exposed to the toxin lipopolysaccharides (LPS), (2) preserved SHSY-5Y cell survival exposed to β-N-methylamino-l-alanine (L-BMAA) neurotoxin, and (3) mitigated motor symptoms and improved survival rate of SOD1G93A ALS mice. In conclusion, the findings of the present work support the potential of the synthesized indolylacetic derivatives II-IV in ALS treatment. Indeed, in the attempt to realize an association between two active molecules, we assumed that the combination of the indispensable moieties of two small molecules (the opioids containing a 4-piperidinyl ring with the FANS indomethacin) might lead to new medicaments potentially useful for the treatment of amyotrophic lateral sclerosis.}, } @article {pmid39020237, year = {2024}, author = {Yuan, ZL and Ren, J and Huang, ML and Qi, YF and Gao, X and Sun, YY and He, YL and Zhu, L and Xue, HD}, title = {A new magnetic resonance imaging-based PUMCH classification system for congenital cervical malformations: devising a standardised diagnosis pathway.}, journal = {Insights into imaging}, volume = {15}, number = {1}, pages = {177}, pmid = {39020237}, issn = {1869-4101}, support = {2022-PUMCH-A-004//National High Level Hospital Clinical Research Funding/ ; 2022-PUMCH-A-004//National High Level Hospital Clinical Research Funding/ ; 2022-PUMCH-A-004//National High Level Hospital Clinical Research Funding/ ; 2022-PUMCH-A-004//National High Level Hospital Clinical Research Funding/ ; }, abstract = {OBJECTIVES: To develop an innovative magnetic resonance imaging (MRI)-based PUMCH (Peking Union Medical College Hospital) classification system aimed at standardising the diagnosis of congenital cervical malformations (CCMs) by identifying their distinctive MRI features.

METHODS: Seventy-nine consecutive patients with CCM underwent pre-treatment pelvic MRI; three experienced gynaecological radiologists retrospectively analysed these images. Qualitative assessments included Rock et al's classification; PUMCH classification; haematometra; cervical signal features; ovarian endometriosis; haematosalpinx; and uterine, vaginal, urinary, and musculoskeletal malformations. Quantitative assessments involved the uterine volume, sagittal cervical length, and maximum ovarian cross-sectional area. The surgical treatment types were also recorded. Statistical methods were used to incorporate differences in clinical features and surgical methods into our classification.

RESULTS: Morphologically, CCMs were categorised into three types: type I (53%) was characterised by the presence of a cervix with visible cervical canals; type II (23%) featured an existing cervix with concealed cervical canals; and type III (24%) indicated cervical aplasia, which involves a blind end in the lower part of the uterine corpus. Haematometra was significantly more prevalent in patients with type I CCM than in those with type II (p < 0.001). There were three cervical signal patterns: no signal (27%), no evident layer differentiation (21%), and multi-layer differentiation with haematocele (52%). Most patients (94%) had complete vaginal atresia. Type I CCM patients had a higher likelihood of regaining normal uterovaginal anatomy compared to types II and III.

CONCLUSIONS: Our proposed PUMCH classification system has a high potential for enhancing the efficiency of clinical diagnosis among patients with CCM.

CRITICAL RELEVANCE STATEMENT: The proposed new PUMCH classification promised to elevate the conventional diagnostic trajectory for congenital cervical malformations, offering a valuable framework to refine the selection and planning of surgical interventions, thereby enhancing overall clinical efficacy.

KEY POINTS: Effective classification of congenital cervical malformations is desirable to optimise the diagnostic process. We presented a PUMCH classification of congenital cervical malformations using pelvic MRI. The new classification significantly aids clinical triage for congenital cervical malformations.}, } @article {pmid39019674, year = {2024}, author = {Georges, M and Perez, T and Rabec, C and Jacquin, L and Finet-Monnier, A and Ramos, C and Patout, M and Attali, V and Amador, M and Gonzalez-Bermejo, J and Salachas, F and Morelot-Panzini, C}, title = {[Proposals from a French expert panel for respiratory care in ALS patients].}, journal = {Revue des maladies respiratoires}, volume = {41}, number = {8}, pages = {620-637}, doi = {10.1016/j.rmr.2024.06.006}, pmid = {39019674}, issn = {1776-2588}, mesh = {*Amyotrophic Lateral Sclerosis/complications/therapy ; Humans ; France/epidemiology ; *Noninvasive Ventilation/methods/standards/instrumentation ; *Respiratory Insufficiency/therapy/etiology ; Respiratory Therapy/methods/standards ; Quality of Life ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive diaphragm weakness and deteriorating lung function. Bulbar involvement and cough weakness contribute to respiratory morbidity and mortality. ALS-related respiratory failure significantly affects quality of life and is the leading cause of death. Non-invasive ventilation (NIV), which is the main recognized treatment for alleviating the symptoms of respiratory failure, prolongs survival and improves quality of life. However, the optimal timing for the initiation of NIV is still a matter of debate. NIV is a complex intervention. Multiple factors influence the efficacy of NIV and patient adherence. The aim of this work was to develop practical evidence-based advices to standardize the respiratory care of ALS patients in French tertiary care centres.

METHODS: For each proposal, a French expert panel systematically searched an indexed bibliography and prepared a written literature review that was then shared and discussed. A combined draft was prepared by the chairman for further discussion. All of the proposals were unanimously approved by the expert panel.

RESULTS: The French expert panel updated the criteria for initiating NIV in ALS patients. The most recent criteria were established in 2005. Practical advice for NIV initiation were included and the value of each tool available for NIV monitoring was reviewed. A strategy to optimize NIV parameters was suggested. Revisions were also suggested for the use of mechanically assisted cough devices in ALS patients.

CONCLUSION: Our French expert panel proposes an evidence-based review to update the respiratory care recommendations for ALS patients in daily practice.}, } @article {pmid39019135, year = {2024}, author = {Cao, M and Yi, L and Xu, Y and Tian, Y and Li, Z and Bi, Y and Guo, M and Li, Y and Liu, Y and Xu, X and Sun, J and Li, C and Duan, W}, title = {Inhibiting NF-κB inducing kinase improved the motor performance of ALS animal model.}, journal = {Brain research}, volume = {1843}, number = {}, pages = {149124}, doi = {10.1016/j.brainres.2024.149124}, pmid = {39019135}, issn = {1872-6240}, mesh = {Animals ; Male ; Mice ; *Amyotrophic Lateral Sclerosis/metabolism/genetics/drug therapy ; *Disease Models, Animal ; Mice, Inbred C57BL ; *Mice, Transgenic ; *NF-kappa B/metabolism ; *NF-kappaB-Inducing Kinase ; *Protein Serine-Threonine Kinases/metabolism/genetics ; Superoxide Dismutase-1/genetics/metabolism ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a typical neurodegenerative disorder typically characterized by inflammation activation. However, the relationship between non-canonical NF-κB (ncNF-κB) pathway activation and ALS progression is not clear.

METHODS: We tested the ncNF-κB pathway in the ALS animal model including hSOD1-G93A transgenic mice and TBK1 deletion mice.We treated age-matched SOD1-G93A mice with B022 (a NIK inhibitor) to investigate the role of NIK in the ALS animal model. We also established a new mice model by crossing SOD1-G93A mice with NIK[+/-] mice to further evaluate the interrelationship between the NIK and the disease progression in ALS animal model.

RESULTS: In this study, we found the ncNF-κB pathway was activated in SOD1-G93A animal model and TBK1 deletion model. Inhibition of NIK activity by small molecule B022 significantly improved the motor performance of the ALS animal model. However, NIK deletion enhanced the mutant SOD1 toxicity by inflammatory infiltration.

CONCLUSION: TBK1 deletion and mutant SOD1 shared the common pathological feature possibly via effects on NIK activation and inhibitor of NIK could be a novel strategy for treating ALS.}, } @article {pmid39017978, year = {2025}, author = {Vinceti, M and Urbano, T and Filippini, T and Bedin, R and Simonini, C and Sorarù, G and Trojsi, F and Michalke, B and Mandrioli, J}, title = {Changes in Cerebrospinal Fluid Concentrations of Selenium Species Induced by Tofersen Administration in Subjects with Amyotrophic Lateral Sclerosis Carrying SOD1 Gene Mutations.}, journal = {Biological trace element research}, volume = {203}, number = {4}, pages = {2355-2364}, pmid = {39017978}, issn = {1559-0720}, support = {"PRIN 2022" (no. 2022MHMRPR)//Ministero dell'Istruzione, dell'Università e della Ricerca/ ; "PRIN 2022 PNRR" (no. P20229KSXB)//Ministero dell'Università e della Ricerca/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/cerebrospinal fluid/drug therapy ; *Selenium/cerebrospinal fluid ; Middle Aged ; *Superoxide Dismutase-1/genetics ; Male ; Female ; *Mutation ; Aged ; *Oligonucleotides/administration & dosage ; Adult ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease affecting the brain and spinal cord motor neurons. On 25 April 2023, the drug tofersen, an antisense oligonucleotide, received the US Food and Drug Administration approval for treating ALS in adults carrying mutations of the SOD1 gene. We aimed at assessing whether cerebrospinal fluid concentrations of selenium, an element of both toxicological and nutritional interest possibly involved in disease etiology and progression, are modified by tofersen administration. We determined concentrations of selenium species by anion exchange chromatography hyphenated to inductively coupled plasma-dynamic reaction cell-mass spectrometry and overall selenium by using inductively coupled plasma sector-field mass spectrometry, at baseline and 6 months after active tofersen treatment in ten Italian ALS patients carrying the SOD1 gene mutation. Concentrations of total selenium and many selenium species substantially increased after the intervention, particularly of inorganic (tetravalent and hexavalent) selenium and of the organic species selenomethionine and a compound co-eluting with the selenocystine standard. Overall, these findings suggest that tofersen treatment markedly alters selenium status and probably the redox status within the central nervous system, possibly due to a direct effect on neurons and/or the blood-brain barrier. Further studies are required to investigate the biological and clinical relevance of these findings and how they might relate to the pharmacological effects of the drug and to disease progression.}, } @article {pmid39017652, year = {2024}, author = {Ranta-Aho, J and Johari, M and Udd, B}, title = {Current advance on distal myopathy genetics.}, journal = {Current opinion in neurology}, volume = {37}, number = {5}, pages = {515-522}, pmid = {39017652}, issn = {1473-6551}, mesh = {Humans ; *Distal Myopathies/genetics/pathology ; }, abstract = {PURPOSE OF REVIEW: Distal myopathies are a clinically heterogenous group of rare, genetic muscle diseases, that present with weakness in hands and/or feet at onset. Some of these diseases remain accentuated in the distal muscles whereas others may later progress to the proximal muscles. In this review, the latest findings related to genetic and clinical features of distal myopathies are summarized.

RECENT FINDINGS: Variants in SMPX , DNAJB2, and HSPB6 have been identified as a novel cause of late-onset distal myopathy and neuromyopathy. In oculopharyngodistal myopathies, repeat expansions were identified in two novel disease-causing genes, RILPL1 and ABCD3. In multisystem proteinopathies, variants in HNRNPA1 and TARDBP , genes previously associated with amyotrophic lateral sclerosis, have been shown to cause late-onset distal myopathy without ALS. In ACTN2 -related distal myopathy, the first recessive forms of the disease have been described, adding it to the growing list of genes were both dominant and recessive forms of myopathy are present.

SUMMARY: The identification of novel distal myopathy genes and pathogenic variants contribute to our ability to provide a final molecular diagnosis to a larger number of patients and increase our overall understanding of distal myopathy genetics and pathology.}, } @article {pmid39015513, year = {2024}, author = {Barahim Bastani, P and Saber Tehrani, AS and Badihian, S and Rieiro, H and Rastall, D and Farrell, N and Parker, M and Otero-Millan, J and Hassoon, A and Newman-Toker, D and Clawson, LL and Uchil, A and Riley, K and Zeiler, SR}, title = {Self-Recording of Eye Movements in Amyotrophic Lateral Sclerosis Patients Using a Smartphone Eye-Tracking App.}, journal = {Digital biomarkers}, volume = {8}, number = {1}, pages = {111-119}, pmid = {39015513}, issn = {2504-110X}, abstract = {INTRODUCTION: Amyotrophic lateral sclerosis (ALS) can affect various eye movements, making eye tracking a potential means for disease monitoring. In this study, we evaluated the feasibility of ALS patients self-recording their eye movements using the "EyePhone," a smartphone eye-tracking application.

METHODS: We prospectively enrolled ten participants and provided them with an iPhone equipped with the EyePhone app and a PowerPoint presentation with step-by-step recording instructions. The goal was for the participants to record their eye movements (saccades and smooth pursuit) without the help of the study team. Afterward, a trained physician administered the same tests using video-oculography (VOG) goggles and asked the participants to complete a questionnaire regarding their self-recording experience.

RESULTS: All participants successfully completed the self-recording process without assistance from the study team. Questionnaire data indicated that participants viewed self-recording with EyePhone favorably, considering it easy and comfortable. Moreover, 70% indicated that they prefer self-recording to being recorded by VOG goggles.

CONCLUSION: With proper instruction, ALS patients can effectively use the EyePhone to record their eye movements, potentially even in a home environment. These results demonstrate the potential for smartphone eye-tracking technology as a viable and self-administered tool for monitoring disease progression in ALS, reducing the need for frequent clinic visits.}, } @article {pmid39015316, year = {2024}, author = {Liu, Y and Chen, Y and Gao, M and Luo, J and Wang, Y and Wang, Y and Gao, Y and Yang, L and Wang, J and Wang, N}, title = {Association between glioma and neurodegenerative diseases risk: a two-sample bi-directional Mendelian randomization analysis.}, journal = {Frontiers in neurology}, volume = {15}, number = {}, pages = {1413015}, pmid = {39015316}, issn = {1664-2295}, abstract = {BACKGROUND: Earlier observational studies have demonstrated a correlation between glioma and the risk of neurodegenerative diseases (NDs), but the causality and direction of their associations remain unclear. The objective of this study was to ascertain the causal link between glioma and NDs using Mendelian randomization (MR) methodology.

METHODS: Genome-wide association study (GWAS) data were used in a two-sample bi-directional MR analysis. From the largest meta-analysis GWAS, encompassing 18,169 controls and 12,488 cases, summary statistics data on gliomas was extracted. Summarized statistics for NDs, including Alzheimer's disease (AD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS) and Parkinson's disease (PD) were obtained from the GWAS of European ancestry. Inverse variance weighted (IVW) method was elected as the core MR approach with weighted median (WM) method and MR-Egger method as complementary methods. In addition, sensitivity analyses were performed. A Bonferroni correction was used to correct the results.

RESULTS: Genetically predicted glioma had been related to decreased risk of AD. Specifically, for all glioma (IVW: OR = 0.93, 95% CI = 0.90-0.96, p = 4.88 × 10[-6]) and glioblastoma (GBM) (IVW: OR = 0.93, 95% CI = 0.91-0.95, p = 5.11 × 10[-9]). We also found that genetically predicted all glioma has a suggestive causative association with MS (IVW: OR = 0.90, 95% CI = 0.81-1.00, p = 0.045). There was no evidence of causal association between glioma and ALS or PD. According to the results of reverse MR analysis, no discernible causal connection of NDs was found on glioma. Sensitivity analyses validated the robustness of the above associations.

CONCLUSION: We report evidence in support of potential causal associations of different glioma subtypes with AD and MS. More studies are required to uncover the underlying mechanisms of these findings.}, } @article {pmid39010704, year = {2024}, author = {Liu, J and Shi, X and Shao, Y}, title = {Sodium-glucose cotransporter 1/2 inhibition and risk of neurodegenerative disorders: A Mendelian randomization study.}, journal = {Brain and behavior}, volume = {14}, number = {7}, pages = {e3624}, pmid = {39010704}, issn = {2162-3279}, mesh = {Humans ; *Mendelian Randomization Analysis ; *Sodium-Glucose Transporter 2 Inhibitors/pharmacology ; *Polymorphism, Single Nucleotide ; *Neurodegenerative Diseases/genetics ; *Glycated Hemoglobin/metabolism ; *Sodium-Glucose Transporter 1/genetics ; Diabetes Mellitus, Type 2/drug therapy/genetics ; Sodium-Glucose Transporter 2/genetics/metabolism ; Parkinson Disease/genetics/drug therapy ; Amyotrophic Lateral Sclerosis/genetics/drug therapy ; Alzheimer Disease/genetics/drug therapy ; Multiple Sclerosis/drug therapy/genetics ; }, abstract = {INTRODUCTION: This study aims to evaluate the effects of sodium-glucose cotransporter 1 inhibitors (SGLT1i) and sodium-glucose cotransporter 2 inhibitors (SGLT2i) on neurodegenerative disorders and to investigate the role of hemoglobin A1c (HbA1c) levels.

METHODS: Utilizing drug target Mendelian randomization, we employed single nucleotide polymorphisms (SNPs) proximal to the SLC5A1 and SLC5A2 genes to analyze the influence of SGLT1i and SGLT2i on Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), frontotemporal dementia (FTD), Lewy body dementia (LBD), and amyotrophic lateral sclerosis (ALS), with type 2 diabetes (T2D) as a positive control. An additional analysis examined the impact of HbA1c levels on the same disorders.

RESULTS: SGLT1i exhibited a significant association with decreased risk for ALS and MS. Conversely, SGLT2i were linked to an increased risk of AD, PD, and MS. Elevated HbA1c levels, independent of SGLT1 and SGLT2 effects, were associated with an increased risk of PD. Sensitivity analyses supported the robustness of these findings.

CONCLUSION: Our study suggests that SGLT1i may confer protection against ALS and MS, whereas SGLT2i could elevate the risk of AD, PD, and MS. Additionally, elevated HbA1c levels emerged as a risk factor for PD. These findings underscore the importance of personalized approaches in the utilization of SGLT inhibitors, considering their varying impacts on the risks of neurodegenerative diseases.}, } @article {pmid39009686, year = {2024}, author = {Neupane, K and Narayan, A and Sen Mojumdar, S and Adhikari, G and Garen, CR and Woodside, MT}, title = {Direct observation of prion-like propagation of protein misfolding templated by pathogenic mutants.}, journal = {Nature chemical biology}, volume = {20}, number = {9}, pages = {1220-1226}, pmid = {39009686}, issn = {1552-4469}, support = {N/A//Gouvernement du Canada | National Research Council Canada (Conseil national de recherches Canada)/ ; RGPIN-2018-04673//Gouvernement du Canada | Natural Sciences and Engineering Research Council of Canada (Conseil de Recherches en Sciences Naturelles et en Génie du Canada)/ ; N/A//Gouvernement du Canada | Natural Sciences and Engineering Research Council of Canada (Conseil de Recherches en Sciences Naturelles et en Génie du Canada)/ ; PJT-185931//Gouvernement du Canada | Canadian Institutes of Health Research (Instituts de Recherche en Santé du Canada)/ ; N/A//Alberta Innovates | Alberta Innovates - Health Solutions (AIHS)/ ; }, mesh = {*Protein Folding ; *Superoxide Dismutase-1/genetics/metabolism/chemistry ; Humans ; *Mutation ; *Prions/metabolism/genetics/chemistry ; Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology ; Optical Tweezers ; }, abstract = {Many neurodegenerative diseases feature misfolded proteins that propagate via templated conversion of natively folded molecules. However, crucial questions about how such prion-like conversion occurs and what drives it remain unsolved, partly because technical challenges have prevented direct observation of conversion for any protein. We observed prion-like conversion in single molecules of superoxide dismutase-1 (SOD1), whose misfolding is linked to amyotrophic lateral sclerosis. Tethering pathogenic misfolded SOD1 mutants to wild-type molecules held in optical tweezers, we found that the mutants vastly increased misfolding of the wild-type molecule, inducing multiple misfolded isoforms. Crucially, the pattern of misfolding was the same in the mutant and converted wild-type domains and varied when the misfolded mutant was changed, reflecting the templating effect expected for prion-like conversion. Ensemble measurements showed decreased enzymatic activity in tethered heterodimers as conversion progressed, mirroring the single-molecule results. Antibodies sensitive to disease-specific epitopes bound to the converted protein, implying that conversion produced disease-relevant misfolded conformers.}, } @article {pmid39009447, year = {2024}, author = {Akter, M and Sepehrimanesh, M and Xu, W and Ding, B}, title = {Assembling a Coculture System to Prepare Highly Pure Induced Pluripotent Stem Cell-Derived Neurons at Late Maturation Stages.}, journal = {eNeuro}, volume = {11}, number = {7}, pages = {}, pmid = {39009447}, issn = {2373-2822}, mesh = {*Induced Pluripotent Stem Cells/physiology ; *Coculture Techniques ; Animals ; *Motor Neurons/physiology ; Mice ; *Astrocytes/physiology ; Humans ; Cell Differentiation/physiology ; Cells, Cultured ; Neurogenesis/physiology ; }, abstract = {Generation of human induced pluripotent stem cell (hiPSC)-derived motor neurons (MNs) offers an unprecedented approach to modeling movement disorders such as dystonia and amyotrophic lateral sclerosis. However, achieving survival poses a significant challenge when culturing induced MNs, especially when aiming to reach late maturation stages. Utilizing hiPSC-derived motor neurons and primary mouse astrocytes, we assembled two types of coculture systems: direct coculturing of neurons with astrocytes and indirect coculture using culture inserts that physically separate neurons and astrocytes. Both systems significantly enhance neuron survival. Compared with these two systems, no significant differences in neurodevelopment, maturation, and survival within 3 weeks, allowing to prepare neurons at maturation stages. Using the indirect coculture system, we obtained highly pure MNs at the late mature stage from hiPSCs. Transcriptomic studies of hiPSC-derived MNs showed a typical neurodevelopmental switch in gene expression from the early immature stage to late maturation stages. Mature genes associated with neurodevelopment and synaptogenesis are highly enriched in MNs at late stages, demonstrating that these neurons achieve maturation. This study introduces a novel tool for the preparation of highly pure hiPSC-derived neurons, enabling the determination of neurological disease pathogenesis in neurons at late disease onset stages through biochemical approaches, which typically necessitate highly pure neurons. This advancement is particularly significant in modeling age-related neurodegeneration.}, } @article {pmid39009032, year = {2024}, author = {Scheithauer, S and Hoffmann, J and Lang, C and Fenz, D and Berens, MM and Köster, AM and Panchyrz, I and Harst, L and Adorjan, K and Apfelbacher, C and Ciesek, S and Denkinger, CM and Drosten, C and Geraedts, M and Hecker, R and Hoffmann, W and Karch, A and Koch, T and Krefting, D and Lieb, K and Meerpohl, JJ and Rehfuess, EA and Skoetz, N and Sopka, S and von Lengerke, T and Wiegand, H and Schmitt, J}, title = {Pandemic Preparedness - A Proposal for a Research Infrastructure and its Functionalities for a Resilient Health Research System.}, journal = {Gesundheitswesen (Bundesverband der Arzte des Offentlichen Gesundheitsdienstes (Germany))}, volume = {}, number = {}, pages = {}, doi = {10.1055/a-2365-9179}, pmid = {39009032}, issn = {1439-4421}, support = {01KX2121//Bundesministerium für Bildung und Forschung/ ; }, abstract = {Während einer Pandemie muss Resilienz nicht nur als Eigenschaft des Gesundheitssystems, sondern auch des umgebenden Forschungsumfelds betrachtet werden. Um verlässliche, evidenzbasierte Empfehlungen aus der Universitätsmedizin an die Gesundheitspolitik und die Entscheidungsträger bereitstellen zu können, müssen wissenschaftliche Erkenntnisse schnell, integrativ und multidisziplinär generiert, synthetisiert und kommuniziert werden. Die Resilienz der öffentlichen Gesundheitssysteme und der Gesundheitsforschungssysteme sind somit eng verknüpft. Die Reaktion auf die SARS-CoV-2-Pandemie in Deutschland wurde jedoch durch das Fehlen einer adäquat vernetzten Gesundheitsforschungsinfrastruktur erschwert. Das Netzwerk Universitätsmedizin (NUM) wurde zu Beginn der Pandemie mit dem Ziel gegründet, Deutschland auf zukünftige Pandemien vorzubereiten. Ziel des Projektes "PREparedness and PAndemic REsponse in Deutschland (PREPARED)" ist es, ein ganzheitliches Konzept für eine kooperative, adaptierbare und nachhaltige Gesundheitsforschungsinfrastruktur innerhalb des NUM zu entwickeln und damit einen Beitrag zu einer umfassenden Pandemiebereitschaft zu leisten. Das vorgeschlagene Konzept dieser Infrastruktur vereint vier Kern- und drei Unterstützungsfunktionalitäten in vier verschiedenen Handlungsfeldern. Die Funktionalitäten gewährleisten im Falle zukünftiger Gesundheitskrisen ein effizientes Funktionieren des Gesundheitsforschungssystems und eine rasche Übertragung entsprechender Implikationen in andere Systeme. Die vier Handlungsfelder sind (a) Monitoring und Surveillance, (b) Synthese und Transfer, (c) Koordination und Organisation sowie (d) Kapazitäten und Ressourcen. Die sieben Funktionalitäten umfassen 1) eine Monitoring- und Surveillance-Einheit, 2) eine Pathogenkompetenz-Plattform, 3) Evidenzsynthese und vertrauenswürdige Empfehlungen, 4) eine Einheit zur regionalen Vernetzung und Implementierung, 5) eine Strategische Kommunikationseinheit, 6) Human Resources Management und 7) ein Rapid Reaction & Response (R[3])-Cockpit. Die Governance wird als Kontroll- und Regulierungssystem eingerichtet, wobei agile Management-Methoden in interpandemischen Phasen trainiert werden, um die Reaktionsfähigkeit zu verbessern sowie die Eignung agiler Methoden für die wissenschaftliche Infrastruktur für die Pandemiebereitschaft zu untersuchen. Der Aufbau der PREPARED-Forschungsinfrastruktur muss vor der nächsten Pandemie erfolgen, da Training und regelmäßige Stresstests grundlegende Voraussetzungen für deren Funktionieren sind.During a pandemic, resilience must be considered not only as an attribute of the health care system, but also of the surrounding research environment. To provide reliable evidence-based advice from university medicine to health policy and decision makers, scientific evidence must be generated, synthesized and communicated in a rapid, integrative and multidisciplinary manner. The resilience of public health systems and the health research systems are thus closely linked. However, the response to the SARS-CoV-2 pandemic in Germany was hampered by the lack of an adequate health research infrastructure. The Network University Medicine (NUM) was founded at the beginning of the pandemic with the aim of preparing Germany for future pandemics. The aim of the project "PREparedness and PAndemic REsponse in Deutschland (PREPARED)" is to develop a holistic concept for a cooperative, adaptable and sustainable health research infrastructure within the NUM and thus contribute to pandemic preparedness and rapid response. The proposed concept for a health research infrastructure includes four core and three supporting functionalities in four different fields of action. The functionalities aim to ensure efficient functioning within the health research system and a rapid translation to other systems in future health crises. The four fields of action are (a) monitoring and surveillance, (b) synthesis and transfer, (c) coordination and organization, and (d) capacities and resources. The seven functionalities include 1) a monitoring and surveillance unit, 2) a pathogen competence platform, 3) evidence synthesis and trustworthy recommendations, 4) a regional networking and implementation unit, 5) a strategic communication unit, 6) human resources management, and 7) a rapid reaction and the response (R[3])-cockpit. A governance will be established as a control and regulatory system for all structures and processes, testing agile management in non-pandemic times to improve responsiveness and flexibility and to investigate the suitability of the methods for scientific pandemic preparedness. The establishment of the PREPARED health research infrastructure must take place before the next pandemic, as training and regular stress tests are its fundamental prerequisites.}, } @article {pmid39008674, year = {2024}, author = {Mason, AH and Motta, A and Kratish, Y and Marks, TJ}, title = {Demystifying group-4 polyolefin hydrogenolysis catalysis. Gaseous propane hydrogenolysis mechanism over the same catalysts.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {121}, number = {30}, pages = {e2406133121}, pmid = {39008674}, issn = {1091-6490}, support = {DE-FG02-03ER15457//DOE | Office of Science (SC)/ ; DOE DE-SC0024448//Dow Chemical Company (Dow)/ ; ECCS-2025633//National Science Foundation (NSF)/ ; NNA04CC36G//NASA | Ames Research Center (ARC)/ ; DOE DE-SC0001329//Dow Chemical Company (Dow)/ ; HP10CPXHA1 2023//CINECA HPC/ ; }, abstract = {A kinetic/mechanistic investigation of gaseous propane hydrogenolysis over the single-site heterogeneous polyolefin depolymerization catalysts AlS/ZrNp2 and AlS/HfNp2 (AlS = sulfated alumina, Np = neopentyl), is use to probe intrinsic catalyst properties without the complexities introduced by time- and viscosity-dependent polymer medium effects. In a polymer-free automated plug-flow catalytic reactor, propane hydrogenolysis turnover frequencies approach 3,000 h[-1] at 150 °C. Both catalysts exhibit approximately linear relationships between rate and [H2] at substoichiometric [H2] with rate law orders of 0.66 ± 0.09 and 0.48 ± 0.07 for Hf and Zr, respectively; at higher [H2], the rates approach zero-order in [H2]. Reaction orders in [C3H8] and [catalyst] are essentially zero-order under all conditions, with the former implying rapid, irreversible alkane binding/activation. This rate law, activation parameter, and DFT energy span analysis support a scenario in which [H2] is pivotal in one of two plausible and competing rate-determining transition states-bimolecular metal-alkyl bond hydrogenolysis vs. unimolecular β-alkyl elimination. The Zr and Hf catalyst activation parameters, ΔH[‡] = 16.8 ± 0.2 kcal mol[-1] and 18.2 ± 0.6 kcal mol[-1], respectively, track the relative turnover frequencies, while ΔS[‡] = -19.1 ± 0.8 and -16.7 ± 1.4 cal mol[-1] K[-1], respectively, imply highly organized transition states. These catalysts maintain activity up to 200 °C, while time-on-stream data indicate multiday activities with an extrapolated turnover number ~92,000 at 150 °C for the Zr catalyst. This methodology is attractive for depolymerization catalyst discovery and process optimization.}, } @article {pmid39008617, year = {2024}, author = {Tsitkanou, S and Lindsay, A and Abbott, G and Foletta, V and Walker, AK and Russell, AP and Della Gatta, PA}, title = {Exercise training induces mild skeletal muscle adaptations without altering disease progression in a TDP-43 mouse model.}, journal = {Journal of applied physiology (Bethesda, Md. : 1985)}, volume = {137}, number = {3}, pages = {728-745}, doi = {10.1152/japplphysiol.00192.2023}, pmid = {39008617}, issn = {1522-1601}, support = {//Deakin University | Institute for Physical Activity and Nutrition (IPAN)/ ; //Onassis Foundation Greece/ ; //Deakin University, Alfread Deakin PostDoc Fellowship/ ; //Neurological Foundation of New Zealand/ ; 1124005//Australian National Health and Medical Research Council/ ; //Ross Maclean Fellowship/ ; //Bill Guest FightMND Mid-Career Development Fellowship/ ; //Brazil Family Program for Neurology/ ; }, mesh = {Animals ; *Disease Progression ; *Muscle, Skeletal/metabolism/physiopathology ; Mice ; *Physical Conditioning, Animal/physiology/methods ; *Adaptation, Physiological/physiology ; *Disease Models, Animal ; *DNA-Binding Proteins/metabolism ; *Amyotrophic Lateral Sclerosis/physiopathology/metabolism/therapy ; Male ; Mice, Transgenic ; }, abstract = {Exercise training is considered a nonpharmacological therapeutic approach for many diseases. Mild-to-moderate endurance exercise training is suggested to improve the mental and physical state of people with amyotrophic lateral sclerosis (ALS). The aim of the present study was to determine the capacity of symptomatic rNLS8 mice, which develop ALS-reminiscent TAR DNA-binding protein 43 (TDP-43) pathology and motor dysfunction, to perform mild-to-moderate intensity treadmill exercise training and to evaluate the effects of this training on skeletal muscle health and disease progression. Symptomatic rNLS8 mice were able to complete 4 wk of mild-to-moderate treadmill running (30 min at 6-13 m/min, 3 days a week). Exercise training induced an increase in the percentage of type IIA fibers in the tibialis anterior muscle as well as minor adaptations in molecular markers of myogenic, mitochondrial, and neuromuscular junction health in some forelimb and hindlimb muscles. However, this exercise training protocol did not attenuate the loss in motor function or delay disease progression. Alternative exercise regimens need to be investigated to better understand the role exercise training may play in alleviating symptoms of ALS.NEW & NOTEWORTHY This is the first study to investigate the capacity of symptomatic rNLS8 mice, which develop ALS-reminiscent TDP-43 pathology and motor dysfunction, to perform exercise training. We demonstrate that despite the ALS-reminiscent aggressive disease progression characterizing the rNLS8 mouse model, rNLS8 mice are capable of performing mild-to-moderate endurance treadmill training for at least 3-4 wk. We demonstrate that exercise training induces several minor skeletal muscle adaptations without delaying disease progression in rNLS8 mice.}, } @article {pmid39007704, year = {2024}, author = {Gandhi, P and Waito, AA and Peladeau-Pigeon, M and Plowman, EK and Steele, CM}, title = {How Do Quantitative Videofluoroscopy Measures Differ Between People With Amyotrophic Lateral Sclerosis and Age-Matched Healthy Adults?.}, journal = {Journal of speech, language, and hearing research : JSLHR}, volume = {67}, number = {8}, pages = {2512-2532}, pmid = {39007704}, issn = {1558-9102}, support = {R01 AG077481/AG/NIA NIH HHS/United States ; R01 DC011020/DC/NIDCD NIH HHS/United States ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology/diagnostic imaging/complications ; Male ; Female ; Aged ; Middle Aged ; Fluoroscopy/methods ; *Deglutition Disorders/physiopathology/etiology/diagnostic imaging ; Aged, 80 and over ; Retrospective Studies ; *Deglutition/physiology ; *Video Recording ; Case-Control Studies ; }, abstract = {PURPOSE: Dysphagia is a leading cause of morbidity in people with amyotrophic lateral sclerosis (PwALS). Previous videofluoroscopic swallowing studies (VFSS) in PwALS do not account for the influence of senescence. We aimed to compare swallowing in PwALS and an age- and sex-matched control group using healthy reference data to define typical and atypical values.

METHOD: We conducted retrospective analysis of VFSS data from 19 PwALS (10 male, Mage = 63 years, range: 47-82) compared to control data from a cohort of healthy adults. Participants swallowed 20% w/v liquid barium from thin to extremely thick consistency. Blinded duplicate VFSS analysis using the ASPEKT (Analysis of Swallowing Physiology: Events, Kinematics and Timing) method yielded descriptive statistics for 16 quantitative VFSS parameters by consistency. Mann-Whitney U tests were used to identify significant cohort differences. Additionally, the frequencies of atypical values (in the 25% tails of the reference distribution) were tabulated by cohort and compared using odds ratios.

RESULTS: PwALS showed increased frequencies of multiple swallows per bolus, incomplete laryngeal vestibule closure, and reduced hyoid speed across consistencies. By contrast, similar frequencies of atypical values for pharyngeal constriction and residue in both cohorts suggest that age-related changes may contribute to the presence of these features in PwALS.

CONCLUSIONS: This analysis builds on previous descriptions of swallowing pathophysiology in amyotrophic lateral sclerosis (ALS) by clarifying the extent to which aging may account for some of the atypical findings seen in this patient population. Longitudinal studies are recommended to further differentiate the effects of ALS from age-related changes in swallowing over the course of disease progression.}, } @article {pmid39007446, year = {2024}, author = {Torra, J and Mora, G and Montull, JM and Royo-Esnal, A and Notter, JS and Salas, M}, title = {A 4-year field study monitoring the evolution of Trp574Leu-resistant plants in an Echinochloa crus-galli population under different crop rotation and herbicide programs in maize.}, journal = {Pest management science}, volume = {80}, number = {11}, pages = {5843-5851}, doi = {10.1002/ps.8315}, pmid = {39007446}, issn = {1526-4998}, support = {//Corteva Agriscience/ ; RYC2018-023866-I//Spanish Ministry of Science, Innovation, and Universities/ ; //Spanish State Research Agency/ ; PID2020-113229RB-C42//European Regional Development Fund (ERDF)/ ; }, mesh = {*Echinochloa/drug effects/genetics ; *Zea mays/growth & development ; *Herbicide Resistance ; *Herbicides/pharmacology ; *Weed Control/methods ; *Plant Weeds/drug effects ; *Acetolactate Synthase/antagonists & inhibitors/metabolism ; Agriculture/methods ; }, abstract = {BACKGROUND: A 4-year experiment evaluated the effects of different integrated weed management (IWM) programs on the evolution of a Echinochloa crus-galli population resistant to acetolactate synthase (ALS) inhibitors in a maize cropping system. The programs included the continued use of ALS inhibitors, mixing them with alternative herbicides, or without ALS-inhibitors, in all cases under maize monocrop or a biennial crop rotation.

RESULTS: IWM programs that relied solely on non-ALS-inhibitors usually achieved high control levels across years (> 90%). Additionally, Trp574Leu-resistant plants became prevalent (> 90%) in programs only using ALS inhibitors, while in the rest the frequency of susceptible plants did not substantially decrease below 40%. Regarding the other monitored grass weeds, Digitaria sanguinalis and Panicum dichotomiflorum were effectively controlled in programs using ALS-inhibitors without soybean rotation or in programs without ALS-inhibitors altogether, excepting the program relying on an 4-hydroxyphenylpyruvate dioxygenase (HPPD)-inhibitor under maize monocrop for the latter species (0%).

CONCLUSION: At the end of the experiment, the only IWM programs that reduced infestation levels were the one without ALS-inhibitors under soybean rotation, and the one with standard pre-emergence treatments. These findings highlight the effectiveness of crop rotation and alternative herbicides both pre- or post-emergence in controlling E. crus-galli. ALS-inhibitors, while challenged by resistance in E. crus-galli, remain valuable tools for managing other grass weed species in maize. It is crucial to adapt IWM strategies for herbicide-resistant E. crus-galli and other grass weed populations to mitigate the further evolution of resistance. © 2024 Corteva Agriscience. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.}, } @article {pmid39007083, year = {2024}, author = {Chidambaram, SB and Anand, N and Varma, SR and Ramamurthy, S and Vichitra, C and Sharma, A and Mahalakshmi, AM and Essa, MM}, title = {Superoxide dismutase and neurological disorders.}, journal = {IBRO neuroscience reports}, volume = {16}, number = {}, pages = {373-394}, pmid = {39007083}, issn = {2667-2421}, abstract = {Superoxide dismutase (SOD) is a common antioxidant enzyme found majorly in living cells. The main physiological role of SOD is detoxification and maintain the redox balance, acts as a first line of defence against Reactive nitrogen species (RNS), Reactive oxygen species (ROS), and other such potentially hazardous molecules. SOD catalyses the conversion of superoxide anion free radicals (O 2 -.) into molecular oxygen (O 2) and hydrogen peroxide (H 2O 2) in the cells. Superoxide dismutases (SODs) are expressed in neurons and glial cells throughout the CNS both intracellularly and extracellularly. Endogenous oxidative stress (OS) linked with enlarged production of reactive oxygen metabolites (ROMs), inflammation, deregulation of redox balance, mitochondrial dysfunction and bioenergetic crisis are found to be prerequisite for neuronal loss in neurological diseases. Clinical and genetic studies indicate a direct correlation between mutations in SOD gene and neurodegenerative diseases, like Amyotrophic Lateral Sclerosis (ALS), Huntington's disease (HD), Parkinson's Disease (PD) and Alzheimer's Disease (AD). Therefore, inhibitors of OS are considered as an optimistic approach to prevent neuronal loss. SOD mimetics like Metalloporphyrin Mn (II)-cyclic polyamines, Nitroxides and Mn (III)- Salen complexes are designed and used as therapeutic extensively in the treatment of neurological disorders. SODs and SOD mimetics are promising future therapeutics in the field of various diseases with OS-mediated pathology.}, } @article {pmid39006832, year = {2023}, author = {Neumann, M and Kothare, H and Ramanarayanan, V}, title = {Combining Multiple Multimodal Speech Features into an Interpretable Index Score for Capturing Disease Progression in Amyotrophic Lateral Sclerosis.}, journal = {Interspeech}, volume = {2023}, number = {}, pages = {2353-2357}, pmid = {39006832}, issn = {2308-457X}, support = {R42 DC019877/DC/NIDCD NIH HHS/United States ; }, abstract = {Multiple speech biomarkers have been shown to carry useful information regarding Amyotrophic Lateral Sclerosis (ALS) pathology. We propose a two-step framework to compute optimal linear combinations (indexes) of these biomarkers that are more discriminative and noise-robust than the individual markers, which is important for clinical care and pharmaceutical trial applications. First, we use a hierarchical clustering based method to select representative speech metrics from a dataset comprising 143 people with ALS and 135 age- and sex-matched healthy controls. Second, we analyze three methods of index computation that optimize linear discriminability, Youden Index, and sparsity of logistic regression model weights, respectively, and evaluate their performance with 5-fold cross validation. We find that the proposed indexes are generally more discriminative of bulbar vs non-bulbar onset in ALS than their individual component metrics as well as an equally-weighted baseline.}, } @article {pmid39006831, year = {2023}, author = {Kothare, H and Neumann, M and Liscombe, J and Green, J and Ramanarayanan, V}, title = {Responsiveness, Sensitivity and Clinical Utility of Timing-Related Speech Biomarkers for Remote Monitoring of ALS Disease Progression.}, journal = {Interspeech}, volume = {2023}, number = {}, pages = {2323-2327}, pmid = {39006831}, issn = {2308-457X}, support = {R42 DC019877/DC/NIDCD NIH HHS/United States ; }, abstract = {In this study, we describe the responsiveness of timing-related measures extracted from read speech in persons with ALS (pALS) collected via a remote patient monitoring platform in an effort to quantify how long it takes to detect a clinically-meaningful change associated with disease progression. We found that the timing alignment of pALS speech relative to a canonical elicitation of the same prompt is the most responsive measure, of the ones considered in this study, at detecting such change in both pALS with bulbar (n = 35) and non-bulbar onset (n = 94). We further evaluated the sensitivity of speech metrics in tracking disease progression in pALS while their ALSFRS-R speech score remained unchanged at 3 out of a total possible score of 4. We observed that timing-related speech metrics showed significant longitudinal changes even after accounting for learning effects. The findings of this study have the potential to inform disease prognosis and functional outcomes of clinical trials.}, } @article {pmid39006764, year = {2024}, author = {Yang, C and Liu, G and Chen, X and Le, W}, title = {Cerebellum in Alzheimer's disease and other neurodegenerative diseases: an emerging research frontier.}, journal = {MedComm}, volume = {5}, number = {7}, pages = {e638}, pmid = {39006764}, issn = {2688-2663}, abstract = {The cerebellum is crucial for both motor and nonmotor functions. Alzheimer's disease (AD), alongside other dementias such as vascular dementia (VaD), Lewy body dementia (DLB), and frontotemporal dementia (FTD), as well as other neurodegenerative diseases (NDs) like Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), and spinocerebellar ataxias (SCA), are characterized by specific and non-specific neurodegenerations in central nervous system. Previously, the cerebellum's significance in these conditions was underestimated. However, advancing research has elevated its profile as a critical node in disease pathology. We comprehensively review the existing evidence to elucidate the relationship between cerebellum and the aforementioned diseases. Our findings reveal a growing body of research unequivocally establishing a link between the cerebellum and AD, other forms of dementia, and other NDs, supported by clinical evidence, pathological and biochemical profiles, structural and functional neuroimaging data, and electrophysiological findings. By contrasting cerebellar observations with those from the cerebral cortex and hippocampus, we highlight the cerebellum's distinct role in the disease processes. Furthermore, we also explore the emerging therapeutic potential of targeting cerebellum for the treatment of these diseases. This review underscores the importance of the cerebellum in these diseases, offering new insights into the disease mechanisms and novel therapeutic strategies.}, } @article {pmid39006715, year = {2024}, author = {Suleiman Khoury, Z and Sohail, F and Wang, J and Mendoza, M and Raake, M and Tahoor Silat, M and Reddy Bathinapatta, M and Sadeghzadegan, A and Meghana, P and Paul, J}, title = {Neuroinflammation: A Critical Factor in Neurodegenerative Disorders.}, journal = {Cureus}, volume = {16}, number = {6}, pages = {e62310}, pmid = {39006715}, issn = {2168-8184}, abstract = {This review offers a comprehensive review of the signals and the paramount role neuroinflammation plays in neurodegenerative diseases such as Alzheimer's, Parkinson's, Huntington's, and amyotrophic lateral sclerosis. The study explores the sophisticated interactions between microglial, astrocytic, and dendritic cells and how neuroinflammation affects long-term neuronal damage and dysfunction. There are specific pathways related to the mentioned inflammatory processes, including Janus kinases/signal transducer and activator of transcriptions, nuclear factor-κB, and mitogen-activated protein kinases pathways. Neuroinflammation is argued to be a double-edged sword, being not only a protective agent that prevents further neuron damage but also the causative factor in more cell injury development. This concept of contrasting inflammation with neuroprotection advocates for the use of therapeutic techniques that seek to modulate neuroinflammatory responses as part of the neurodegeneration treatment. The recent research findings are integrated with the established knowledge to help present a comprehensive image of neuroinflammation's impact on neurodegenerative diseases and its implications for future therapy.}, } @article {pmid39006307, year = {2023}, author = {Ayoubi, R and Alshafie, W and Shlaifer, I and Southern, K and McPherson, PS and Laflamme, C and , }, title = {The identification of high-performing antibodies for Sequestosome-1 for use in Western blot, immunoprecipitation and immunofluorescence.}, journal = {F1000Research}, volume = {12}, number = {}, pages = {324}, pmid = {39006307}, issn = {2046-1402}, mesh = {*Sequestosome-1 Protein/immunology/metabolism ; Humans ; *Fluorescent Antibody Technique/methods ; *Immunoprecipitation/methods ; *Blotting, Western ; Antibodies/immunology ; }, abstract = {Sequestosome-1, encoded by the gene SQSTM1, functions as a bridge between ubiquitinated proteins and the proteasome or autophagosome, thereby regulating protein degradation pathways. Loss of Sequestosome-1 is hypothesized to enhance neurodegeneration progression in several diseases, including amyotrophic lateral sclerosis (ALS) and frontotemporal disorders (FTD). Sequestosome-1 reproducible research would be facilitated with the availability of well-characterized anti-Sequestosome-1 antibodies. In this study, we characterized seventeen Sequestosome-1 commercial antibodies for Western blot, immunoprecipitation, and immunofluorescence using a standardized experimental protocol based on comparing read-outs in knockout cell lines and isogenic parental controls. We identified many high-performing antibodies and encourage readers to use this report as a guide to select the most appropriate antibody for their specific needs.}, } @article {pmid39005475, year = {2024}, author = {Xie, M and Miller, AS and Pallegar, PN and Umpierre, A and Liang, Y and Wang, N and Zhang, S and Nagaraj, NK and Fogarty, ZC and Ghayal, NB and Oskarsson, B and Zhao, S and Zheng, J and Qi, F and Nguyen, A and Dickson, DW and Wu, LJ}, title = {Rod-shaped microglia interact with neuronal dendrites to regulate cortical excitability in TDP-43 related neurodegeneration.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2024.06.30.601396}, pmid = {39005475}, issn = {2692-8205}, support = {RF1 AG082314/AG/NIA NIH HHS/United States ; }, abstract = {Motor cortical hyperexcitability is well-documented in the presymptomatic stage of amyotrophic lateral sclerosis (ALS). However, the mechanisms underlying this early dysregulation are not fully understood. Microglia, as the principal immune cells of the central nervous system, have emerged as important players in sensing and regulating neuronal activity. Here we investigated the role of microglia in the motor cortical circuits in a mouse model of TDP-43 neurodegeneration (rNLS8). Utilizing multichannel probe recording and longitudinal in vivo calcium imaging in awake mice, we observed neuronal hyperactivity at the initial stage of disease progression. Spatial and single-cell RNA sequencing revealed that microglia are the primary responders to motor cortical hyperactivity. We further identified a unique subpopulation of microglia, rod-shaped microglia, which are characterized by a distinct morphology and transcriptional profile. Notably, rod-shaped microglia predominantly interact with neuronal dendrites and excitatory synaptic inputs to attenuate motor cortical hyperactivity. The elimination of rod-shaped microglia through TREM2 deficiency increased neuronal hyperactivity, exacerbated motor deficits, and further decreased survival rates of rNLS8 mice. Together, our results suggest that rod-shaped microglia play a neuroprotective role by attenuating cortical hyperexcitability in the mouse model of TDP-43 related neurodegeneration.}, } @article {pmid39005384, year = {2024}, author = {Dykstra, MM and Weskamp, K and Gómez, NB and Waksmacki, J and Tank, E and Glineburg, MR and Snyder, A and Pinarbasi, E and Bekier, M and Li, X and Bai, J and Shahzad, S and Nedumaran, J and Wieland, C and Stewart, C and Willey, S and Grotewold, N and McBride, J and Moran, JJ and Suryakumar, AV and Lucas, M and Tessier, P and Ward, M and Todd, P and Barmada, SJ}, title = {TDP43 autoregulation gives rise to shortened isoforms that are tightly controlled by both transcriptional and post-translational mechanisms.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {39005384}, issn = {2692-8205}, support = {F31 NS134123/NS/NINDS NIH HHS/United States ; I01 BX004842/BX/BLRD VA/United States ; P30 AG072931/AG/NIA NIH HHS/United States ; R01 NS099280/NS/NINDS NIH HHS/United States ; R01 NS113943/NS/NINDS NIH HHS/United States ; R01 NS097542/NS/NINDS NIH HHS/United States ; R56 NS128110/NS/NINDS NIH HHS/United States ; F31 NS115257/NS/NINDS NIH HHS/United States ; T32 GM145470/GM/NIGMS NIH HHS/United States ; }, abstract = {The nuclear RNA-binding protein TDP43 is integrally involved in the pathogenesis of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Previous studies uncovered N-terminal TDP43 isoforms that are predominantly cytosolic in localization, highly prone to aggregation, and enriched in susceptible spinal motor neurons. In healthy cells, however, these shortened (s)TDP43 isoforms are difficult to detect in comparison to full-length (fl)TDP43, raising questions regarding their origin and selective regulation. Here, we show that sTDP43 is created as a byproduct of TDP43 autoregulation and cleared by nonsense mediated RNA decay (NMD). The sTDP43-encoding transcripts that escape NMD can lead to toxicity but are rapidly degraded post-translationally. Circumventing these regulatory mechanisms by overexpressing sTDP43 results in neurodegeneration in vitro and in vivo via N-terminal oligomerization and impairment of flTDP43 splicing activity, in addition to RNA binding-dependent gain-of-function toxicity. Collectively, these studies highlight endogenous mechanisms that tightly regulate sTDP43 expression and provide insight into the consequences of aberrant sTDP43 accumulation in disease.}, } @article {pmid39005345, year = {2024}, author = {Rizuan, A and Shenoy, J and Mohanty, P and Dos Passos, PMS and Mercado Ortiz, JF and Bai, L and Viswanathan, R and Wang, SH and Johnson, V and Mamede, LD and Ayala, YM and Ghirlando, R and Mittal, J and Fawzi, NL}, title = {Structural details of helix-mediated TDP-43 C-terminal domain multimerization.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {39005345}, issn = {2692-8205}, support = {R01 NS116176/NS/NINDS NIH HHS/United States ; }, abstract = {The primarily disordered C-terminal domain (CTD) of TAR DNA binding protein-43 (TDP-43), a key nuclear protein in RNA metabolism, forms neuronal inclusions in several neurodegenerative diseases. A conserved region (CR, spanning residues 319-341) in CTD forms transient helix-helix contacts important for its higher-order oligomerization and function that are disrupted by ALS-associated mutations. However, the structural details of CR assembly and the explanation for several ALS-associated variants' impact on phase separation and function remain unclear due to challenges in analyzing the dynamic association of TDP-43 CTD using traditional structural biology approaches. By employing an integrative approach, combining biophysical experiments, biochemical assays, AlphaFold2-Multimer (AF2-Multimer), and atomistic simulations, we generated structural models of helical oligomerization of TDP-43 CR. Using NMR, we first established that the native state of TDP-43 CR under physiological conditions is α-helical. Next, alanine scanning mutagenesis revealed that while hydrophobic residues in the CR are important for CR assembly, phase separation and TDP-43 nuclear retention function, polar residues down regulate these processes. Finally, pairing AF2-Multimer modeling with AAMD simulations indicated that dynamic, oligomeric assemblies of TDP-43 that are stabilized by a methionine-rich core with specific contributions from a tryptophan/leucine pair. In conclusion, our results advance the structural understanding of the mechanisms driving TDP-43 function and provide a window into the initial stages of its conversion into pathogenic aggregates.}, } @article {pmid39005286, year = {2024}, author = {Krattli, RP and Do, AH and El-Khatib, SM and Alikhani, L and Markarian, M and Vagadia, AR and Usmani, MT and Madan, S and Baulch, JE and Clark, RJ and Woodruff, TM and Tenner, AJ and Acharya, MM}, title = {C5aR1 inhibition alleviates cranial radiation-induced cognitive decline.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2024.07.02.601806}, pmid = {39005286}, issn = {2692-8205}, abstract = {UNLABELLED: Cranial radiation therapy (RT) for brain cancers leads to an irreversible decline in cognitive function without an available remedy. Radiation-induced cognitive deficits (RICD) are a particularly pressing problem for the survivors of pediatric and low grade glioma (LGG) cancers who often live long post-RT lives. Radiation-induced elevated neuroinflammation and gliosis, triggered by the detrimental CNS complement cascade, lead to excessive synaptic and cognitive loss. Using intact and brain cancer-bearing mouse models, we now show that targeting anaphylatoxin complement C5a receptor (C5aR1) is neuroprotective against RICD. We used a genetic knockout, C5aR1 KO mouse, and a pharmacologic approach, employing the orally active, brain penetrant C5aR1 antagonist PMX205 to reverse RICD. Irradiated C5aR1 KO and WT mice receiving PMX205 showed significant neurocognitive improvements in object recognition memory and memory consolidation tasks. Inhibiting C5a/C5aR1 axis reduced microglial activation, astrogliosis, and synaptic loss in the irradiated brain. Importantly, C5aR1 blockage in two syngeneic, orthotopic glioblastoma-bearing mice protected against RICD without interfering with the therapeutic efficacy of RT to reduce tumor volume in vivo . PMX205 clinical trials with healthy individuals and amyotrophic lateral sclerosis (ALS) patients showed no toxicity, drug-related adverse events, or infections. Thus, C5aR1 inhibition is a translationally feasible approach to address RICD, an unmet medical need.

SIGNIFICANCE: Cranial radiotherapy for brain cancers activates CNS complement cascade, leading to cognitive decline. Ablation of the complement C5a/C5aR1 axis alleviates radiation-induced neuroinflammation, synaptic loss, and cognitive dysfunction, providing a novel tractable approach.}, } @article {pmid39005258, year = {2024}, author = {Feringa, FM and Hertog, SJK and Wang, L and Derks, RJE and Kruijff, I and Erlebach, L and Heijneman, J and Miramontes, R and Pömpner, N and Blomberg, N and Olivier-Jimenez, D and Johansen, LE and Cammack, AJ and Giblin, A and Toomey, CE and Rose, IVL and Yuan, H and Ward, M and Isaacs, AM and Kampmann, M and Kronenberg-Versteeg, D and Lashley, T and Thompson, LM and Ori, A and Mohammed, Y and Giera, M and van der Kant, R}, title = {The Neurolipid Atlas: a lipidomics resource for neurodegenerative diseases uncovers cholesterol as a regulator of astrocyte reactivity impaired by ApoE4.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {39005258}, issn = {2692-8205}, support = {P01 NS084974/NS/NINDS NIH HHS/United States ; P30 CA062203/CA/NCI NIH HHS/United States ; T32 NS115706/NS/NINDS NIH HHS/United States ; }, abstract = {Lipid changes in the brain have been implicated in many neurodegenerative diseases including Alzheimer's Disease (AD), Parkinson's disease and Amyotrophic Lateral Sclerosis. To facilitate comparative lipidomic research across brain-diseases we established a data commons named the Neurolipid Atlas, that we have pre-populated with novel human, mouse and isogenic induced pluripotent stem cell (iPSC)-derived lipidomics data for different brain diseases. We show that iPSC-derived neurons, microglia and astrocytes display distinct lipid profiles that recapitulate in vivo lipotypes. Leveraging multiple datasets, we show that the AD risk gene ApoE4 drives cholesterol ester (CE) accumulation in human astrocytes recapitulating CE accumulation measured in the human AD brain. Multi-omic interrogation of iPSC-derived astrocytes revealed that cholesterol plays a major role in astrocyte interferon-dependent pathways such as the immunoproteasome and major histocompatibility complex (MHC) class I antigen presentation. We show that through enhanced cholesterol esterification ApoE4 suppresses immune activation of astrocytes. Our novel data commons, available at neurolipidatlas.com, provides a user-friendly tool and knowledge base for a better understanding of lipid dyshomeostasis in neurodegenerative diseases.}, } @article {pmid39004530, year = {2024}, author = {Vacchiano, V and Di Stasi, V and Bruni, S and Rizzo, G and Liguori, R}, title = {Thoracic paraspinal muscles denervation assessment in amyotrophic lateral sclerosis: Clinical-neurophysiological correlations and prognostic value.}, journal = {Journal of the neurological sciences}, volume = {463}, number = {}, pages = {123133}, doi = {10.1016/j.jns.2024.123133}, pmid = {39004530}, issn = {1878-5883}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology/diagnosis ; *Paraspinal Muscles/physiopathology ; Male ; Middle Aged ; Female ; Prognosis ; Aged ; Electromyography/methods ; Muscle Denervation/methods ; Adult ; }, } @article {pmid39004370, year = {2024}, author = {Hajdukiewicz, H and Hajdukiewicz, M and Ruiz-Villanueva, V and Radecki-Pawlik, A and Zawiejska, J}, title = {Exploring historical changes in mountain river hydrodynamics induced by human impact.}, journal = {The Science of the total environment}, volume = {948}, number = {}, pages = {174742}, doi = {10.1016/j.scitotenv.2024.174742}, pmid = {39004370}, issn = {1879-1026}, abstract = {During the 20th-century many mountain rivers in Europe were subjected to intensive human impacts which substantially modified their channel morphology. How these changes affected river hydrodynamics and response to floods remains uncertain. In this work, we perform hydraulic modelling using data from archival aerial photos to explore relations between hydraulic parameters of floods and human-induced channel incision occurring on the Czarny Dunajec River (Polish Carpathians) between 1964 and 2012. Data on vertical position of the channel used for two-dimensional modelling of flood flows were extracted (as Digital Elevation Models DEMs) from archival aerial photos from 1964 and 1983 and ALS (Airborne Laser Skanning)-derived DEM from 2012. Water depth, flow velocity, bed shear stress, and sediment critical diameter were modelled for four flood scenarios (2-year, 5-year, 20-year, and 50-year floods) as well as the extent of flooded area and additionally the grain size of channel sediment was calculated. The values of water depth, flow velocity, bed shear stress and sediment critical diameter increased significantly between 1964 and 1983, especially for 20-year and 50-year floods. Only the flow velocity within the floodplain zone did not increase for the two largest flood scenarios due to the expansion of riparian forest in the second half of the twentieth century. The increase in flow rate was accompanied by a progressive reduction of the extent of flooded area, especially between 1964 and 1983, as well as by increase in mean grain size of channel sediment. Between 1983 and 2012 changes in hydraulic parameters were less pronounced, and coarser and well packed channel sediment dominated on the river bed. Our work demonstrates that reconstruction of past river hydrodynamics, rather than river state at time horizons, can give essential insights into functioning of the river channel and floodplain during the intensification of human impacts after 1950s.}, } @article {pmid39003629, year = {2024}, author = {Yao, S and Yin, H and Li, Y and Yang, Q and Yuan, S and Deng, W}, title = {Cytochrome P450 CYP81A104 in Eleusine indica confers resistance to multiherbicide with different modes of action.}, journal = {Pest management science}, volume = {80}, number = {11}, pages = {5791-5798}, doi = {10.1002/ps.8310}, pmid = {39003629}, issn = {1526-4998}, support = {32372569//National Natural Science Foundation of China/ ; 137050535//Qing Lan Project of Yangzhou University/ ; }, mesh = {*Herbicide Resistance/genetics ; *Herbicides/pharmacology ; *Cytochrome P-450 Enzyme System/genetics/metabolism ; *Eleusine/genetics/drug effects/enzymology ; Acetolactate Synthase/genetics/metabolism ; Plant Proteins/genetics/metabolism ; Arabidopsis/genetics/drug effects/enzymology ; Plant Weeds/drug effects/genetics ; Imidazoles ; }, abstract = {BACKGROUND: Developing herbicide-resistant (HR) crop cultivars is an efficient way to control weeds and minimize crop yield losses. However, widespread and long-term herbicide application has led to the evolution of resistant weeds. Here, we established a resistant (R) E. indica population, collected from imidazolinone-resistant rice cultivar fields.

RESULTS: The R population evolved 4.5-fold resistance to imazamox. Acetolactate synthase (ALS) gene sequencing and ALS activity assays excluded the effect of target-site resistance in this population. P450 inhibitor malathion pretreatment significantly reversed resistance to imazamox. RNA sequencing showed that a P450 gene CYP81A104 was expressed higher in R versus susceptible (S) plants. Arabidopsis overexpressing CYP81A104 showed resistance to ALS inhibitors (imazamox, tribenuron-methyl, penoxsulam and flucarbazone-sodium), PSII inhibitor (bentazone), hydroxyphenyl pyruvate dioxygenase inhibitor (mesotrione) and auxin mimics (MCPA), which was generally consistent with the results presented in the R population.

CONCLUSION: This study confirmed that the CYP81A104 gene endowed resistance to multiherbicides with different modes-of-action. Our findings provide an insight into the molecular characteristics of resistance and contribute to formulating an appropriate strategy for weed management in HR crops. © 2024 Society of Chemical Industry.}, } @article {pmid39002811, year = {2024}, author = {Huin, V and Blum, D and Delforge, V and Cailliau, E and Djeziri, S and Dujardin, K and Genet, A and Viard, R and Attarian, S and Bruneteau, G and Cassereau, J and Genestet, S and Kaminsky, AL and Soriani, MH and Lefilliatre, M and Couratier, P and Pittion-Vouyovitch, S and Esselin, F and De La Cruz, E and Guy, N and Kolev, I and Corcia, P and Cintas, P and Desnuelle, C and Buée, L and Danel-Brunaud, V and Devos, D and Rolland, AS}, title = {Caffeine consumption outcomes on amyotrophic lateral sclerosis disease progression and cognition.}, journal = {Neurobiology of disease}, volume = {199}, number = {}, pages = {106603}, doi = {10.1016/j.nbd.2024.106603}, pmid = {39002811}, issn = {1095-953X}, mesh = {Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; *Amyotrophic Lateral Sclerosis/genetics/drug therapy ; Basic Helix-Loop-Helix Transcription Factors ; *Caffeine ; Central Nervous System Stimulants/therapeutic use ; Cognition/physiology/drug effects ; Cognitive Dysfunction/genetics ; Cytochrome P-450 CYP1A1/genetics ; *Cytochrome P-450 CYP1A2/genetics ; *Disease Progression ; *Polymorphism, Single Nucleotide ; Prospective Studies ; *Receptor, Adenosine A2A/genetics ; Receptors, Aryl Hydrocarbon/genetics ; Riluzole/therapeutic use ; }, abstract = {Caffeine consumption outcomes on Amyotrophic Lateral Sclerosis (ALS) including progression, survival and cognition remain poorly defined and may depend on its metabolization influenced by genetic variants. 378 ALS patients with a precise evaluation of their regular caffeine consumption were monitored as part of a prospective multicenter study. Demographic, clinical characteristics, functional disability as measured with revised ALS Functional Rating Scale (ALSFRS-R), cognitive deficits measured using Edinburgh Cognitive and Behavioural ALS Screen (ECAS), survival and riluzole treatment were recorded. 282 patients were genotyped for six single nucleotide polymorphisms tagging different genes involved in caffeine intake and/or metabolism: CYP1A1 (rs2472297), CYP1A2 (rs762551), AHR (rs4410790), POR (rs17685), XDH (rs206860) and ADORA2A (rs5751876) genes. Association between caffeine consumption and ALSFRS-R, ALSFRS-R rate, ECAS and survival were statistically analyzed to determine the outcome of regular caffeine consumption on ALS disease progression and cognition. No association was observed between caffeine consumption and survival (p = 0.25), functional disability (ALSFRS-R; p = 0.27) or progression of ALS (p = 0.076). However, a significant association was found with higher caffeine consumption and better cognitive performance on ECAS scores in patients carrying the C/T and T/T genotypes at rs2472297 (p-het = 0.004). Our results support the safety of regular caffeine consumption on ALS disease progression and survival and also show its beneficial impact on cognitive performance in patients carrying the minor allele T of rs2472297, considered as fast metabolizers, that would set the ground for a new pharmacogenetic therapeutic strategy.}, } @article {pmid39002563, year = {2024}, author = {Shih, PC and Wei, JCC}, title = {Response to Hasan et al's "Dupilumab therapy for atopic dermatitis is associated with increased risk of cutaneous T cell lymphoma: A retrospective cohort study".}, journal = {Journal of the American Academy of Dermatology}, volume = {91}, number = {5}, pages = {e137-e138}, doi = {10.1016/j.jaad.2024.06.076}, pmid = {39002563}, issn = {1097-6787}, } @article {pmid39001793, year = {2024}, author = {Gao, J and Okolo, O and Siedlak, SL and Friedland, RP and Wang, X}, title = {Ferritin is closely associated with microglia in amyotrophic lateral sclerosis.}, journal = {Journal of neuropathology and experimental neurology}, volume = {83}, number = {11}, pages = {917-926}, pmid = {39001793}, issn = {1554-6578}, support = {RF1 AG066578/AG/NIA NIH HHS/United States ; RF1 AG056320/AG/NIA NIH HHS/United States ; R01 AG066578/AG/NIA NIH HHS/United States ; HHSN275200900011C/HD/NICHD NIH HHS/United States ; RF1AG066578/NH/NIH HHS/United States ; AARG-22-923849/ALZ/Alzheimer's Association/United States ; //Brain and Tissue Bank for Developmental Disorders/ ; //Eunice Kennedy Shriver National Institute of Child Health and Human Development/ ; RF1 AG065342/AG/NIA NIH HHS/United States ; }, mesh = {*Amyotrophic Lateral Sclerosis/pathology/metabolism/genetics ; *Microglia/metabolism/pathology ; *Ferritins/metabolism ; Humans ; *Mice, Transgenic ; Animals ; Female ; Male ; Mice ; Middle Aged ; *Spinal Cord/pathology/metabolism ; Aged ; Aged, 80 and over ; DNA-Binding Proteins/metabolism/genetics ; Superoxide Dismutase/metabolism/genetics ; }, abstract = {Iron deposition is a hallmark of amyotrophic lateral sclerosis (ALS) and has been strongly implicated in its pathogenesis. As a byproduct of cellular oxidative stress, iron dysregulation modifies basal levels of the regulatory iron-binding protein ferritin. Examination of thoracic and lumbar spinal cord tissues found increased ferritin immunostaining in white matter axons that corresponded to areas of increased microgliosis in 8 ALS patients versus 8 normal subjects. Gray matter areas containing the motor neurons also demonstrated increased ferritin and microglia in ALS compared to controls but at lower levels than in the white matter. Motor neurons with or without TDP-43 inclusions did not demonstrate either increased ferritin or associated microglial activation. We also observed an association of ferritin with microglia in cerebral cortical tissue samples of ALS cases and in the spinal cord tissues of transgenic mice expressing the SOD1G93A mutation. Elevated ferritin levels were detected in the insoluble fraction from spinal cord tissues of individuals with ALS. These findings suggest that activated microglia and increased ferritin may play significant roles in ALS progression since they are found closely associated in areas of axonal and cortical degeneration.}, } @article {pmid39000814, year = {2024}, author = {Fan, S and Jing, S and Xu, W and Wu, B and Li, M and Jing, H}, title = {Extraction of Moso Bamboo Parameters Based on the Combination of ALS and TLS Point Cloud Data.}, journal = {Sensors (Basel, Switzerland)}, volume = {24}, number = {13}, pages = {}, pmid = {39000814}, issn = {1424-8220}, support = {LTGC23C160002//Zhejiang Provincial Natural Science Foundation of China/ ; 2021LFR057//Research Fund of Zhejiang A&F University/ ; 2023LFK141//Research Fund of Zhejiang A&F University/ ; }, mesh = {*Algorithms ; Sasa ; Lasers ; Poaceae ; }, abstract = {Extracting moso bamboo parameters from single-source point cloud data has limitations. In this article, a new approach for extracting moso bamboo parameters using airborne laser scanning (ALS) and terrestrial laser scanning (TLS) point cloud data is proposed. Using the field-surveyed coordinates of plot corner points and the Iterative Closest Point (ICP) algorithm, the ALS and TLS point clouds were aligned. Considering the difference in point distribution of ALS, TLS, and the merged point cloud, individual bamboo plants were segmented from the ALS point cloud using the point cloud segmentation (PCS) algorithm, and individual bamboo plants were segmented from the TLS and the merged point cloud using the comparative shortest-path (CSP) method. The cylinder fitting method was used to estimate the diameter at breast height (DBH) of the segmented bamboo plants. The accuracy was calculated by comparing the bamboo parameter values extracted by the above methods with reference data in three sample plots. The comparison results showed that by using the merged data, the detection rate of moso bamboo plants could reach up to 97.30%; the R[2] of the estimated bamboo height was increased to above 0.96, and the root mean square error (RMSE) decreased from 1.14 m at most to a range of 0.35-0.48 m, while the R[2] of the DBH fit was increased to a range of 0.97-0.99, and the RMSE decreased from 0.004 m at most to a range of 0.001-0.003 m. The accuracy of moso bamboo parameter extraction was significantly improved by using the merged point cloud data.}, } @article {pmid39000336, year = {2024}, author = {Bodai, L and Borosta, R and Ferencz, Á and Kovács, M and Zsindely, N}, title = {The Role of miR-137 in Neurodegenerative Disorders.}, journal = {International journal of molecular sciences}, volume = {25}, number = {13}, pages = {}, pmid = {39000336}, issn = {1422-0067}, support = {OTKA 145898//National Research, Development and Innovation Office [Hungary]/ ; }, mesh = {*MicroRNAs/genetics/metabolism ; Humans ; *Neurodegenerative Diseases/genetics/metabolism ; Animals ; Gene Expression Regulation ; }, abstract = {Neurodegenerative diseases affect an increasing part of the population of modern societies, burdening healthcare systems and causing immense suffering at the personal level. The pathogenesis of several of these disorders involves dysregulation of gene expression, which depends on several molecular processes ranging from transcription to protein stability. microRNAs (miRNAs) are short non-coding RNA molecules that modulate gene expression by suppressing the translation of partially complementary mRNAs. miR-137 is a conserved, neuronally enriched miRNA that is implicated in neurodegeneration. Here, we review the current body of knowledge about the role that miR-137 plays in five prominent neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and multiple sclerosis. The presented data indicate that, rather than having a general neuroprotective role, miR-137 modulates the pathology of distinct disorders differently.}, } @article {pmid39000168, year = {2024}, author = {Ciuro, M and Sangiorgio, M and Cacciato, V and Cantone, G and Fichera, C and Salvatorelli, L and Magro, G and Leanza, G and Vecchio, M and Valle, MS and Gulino, R}, title = {Mitigating the Functional Deficit after Neurotoxic Motoneuronal Loss by an Inhibitor of Mitochondrial Fission.}, journal = {International journal of molecular sciences}, volume = {25}, number = {13}, pages = {}, pmid = {39000168}, issn = {1422-0067}, support = {2015MJBEM2_006//the Italian "Ministero dell'Istruzione, dell'Università e della Ricerca"/ ; }, mesh = {Animals ; *Motor Neurons/drug effects/metabolism/pathology ; *Mitochondrial Dynamics/drug effects ; Mice ; *Disease Models, Animal ; *Amyotrophic Lateral Sclerosis/metabolism/drug therapy/pathology ; Cholera Toxin/metabolism ; Saporins ; Quinazolinones/pharmacology ; Neuronal Plasticity/drug effects ; Male ; Mitochondria/drug effects/metabolism ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is an extremely complex neurodegenerative disease involving different cell types, but motoneuronal loss represents its main pathological feature. Moreover, compensatory plastic changes taking place in parallel to neurodegeneration are likely to affect the timing of ALS onset and progression and, interestingly, they might represent a promising target for disease-modifying treatments. Therefore, a simplified animal model mimicking motoneuronal loss without the other pathological aspects of ALS has been established by means of intramuscular injection of cholera toxin-B saporin (CTB-Sap), which is a targeted neurotoxin able to kill motoneurons by retrograde suicide transport. Previous studies employing the mouse CTB-Sap model have proven that spontaneous motor recovery is possible after a subtotal removal of a spinal motoneuronal pool. Although these kinds of plastic changes are not enough to counteract the functional effects of the progressive motoneuron degeneration, it would nevertheless represent a promising target for treatments aiming to postpone ALS onset and/or delay disease progression. Herein, the mouse CTB-Sap model has been used to test the efficacy of mitochondrial division inhibitor 1 (Mdivi-1) as a tool to counteract the CTB-Sap toxicity and/or to promote neuroplasticity. The homeostasis of mitochondrial fission/fusion dynamics is indeed important for cell integrity, and it could be affected during neurodegeneration. Lesioned mice were treated with Mdivi-1 and then examined by a series of behavioral test and histological analyses. The results have shown that the drug may be capable of reducing functional deficits after the lesion and promoting synaptic plasticity and neuroprotection, thus representing a putative translational approach for motoneuron disorders.}, } @article {pmid38999600, year = {2024}, author = {Chakraborty, N and Das, A and Pal, S and Roy, S and Sil, SK and Adak, MK and Hassanzamman, M}, title = {Exploring Aluminum Tolerance Mechanisms in Plants with Reference to Rice and Arabidopsis: A Comprehensive Review of Genetic, Metabolic, and Physiological Adaptations in Acidic Soils.}, journal = {Plants (Basel, Switzerland)}, volume = {13}, number = {13}, pages = {}, pmid = {38999600}, issn = {2223-7747}, abstract = {Aluminum (Al) makes up a third of the Earth's crust and is a widespread toxic contaminant, particularly in acidic soils. It impacts crops at multiple levels, from cellular to whole plant systems. This review delves into Al's reactivity, including its cellular transport, involvement in oxidative redox reactions, and development of specific metabolites, as well as the influence of genes on the production of membrane channels and transporters, alongside its role in triggering senescence. It discusses the involvement of channel proteins in calcium influx, vacuolar proton pumping, the suppression of mitochondrial respiration, and the initiation of programmed cell death. At the cellular nucleus level, the effects of Al on gene regulation through alterations in nucleic acid modifications, such as methylation and histone acetylation, are examined. In addition, this review outlines the pathways of Al-induced metabolic disruption, specifically citric acid metabolism, the regulation of proton excretion, the induction of specific transcription factors, the modulation of Al-responsive proteins, changes in citrate and nucleotide glucose transporters, and overall metal detoxification pathways in tolerant genotypes. It also considers the expression of phenolic oxidases in response to oxidative stress, their regulatory feedback on mitochondrial cytochrome proteins, and their consequences on root development. Ultimately, this review focuses on the selective metabolic pathways that facilitate Al exclusion and tolerance, emphasizing compartmentalization, antioxidative defense mechanisms, and the control of programmed cell death to manage metal toxicity.}, } @article {pmid38999592, year = {2024}, author = {Li, Q and Wang, H and Yu, J and Zhang, W and Guo, W and Liu, Y}, title = {Metabolism-Based Herbicide Resistance to Mesosulfuron-methyl and Identification of Candidate Genes in Bromus japonicus.}, journal = {Plants (Basel, Switzerland)}, volume = {13}, number = {13}, pages = {}, pmid = {38999592}, issn = {2223-7747}, support = {23JCQNJC00450//Tianjin Natural Science Foundation/ ; 2021CXGC010811//Key R&D Program of Shandong Province, China/ ; }, abstract = {The evolved resistance of Bromus japonicus Houtt. to ALS-inhibiting herbicides is well established. Previous studies have primarily focused on target-site resistance; however, non-target-site resistance has not been well characterized. This investigation demonstrated that ALS gene sequencing did not detect any previously known resistance mutations in a mesosulfuron-methyl-resistant (MR) population, and notably, treatment with the P450 monooxygenase (P450) inhibitor malathion markedly heightened susceptibility to mesosulfuron-methyl. Utilizing UPLC-MS/MS analysis confirmed elevated mesosulfuron-methyl metabolism in MR plants. The integration of Isoform Sequencing (Iso-Seq) and RNA Sequencing (RNA-Seq) facilitated the identification of candidate genes associated with non-target sites in a subpopulation with two generations of herbicide selection. Through qRT-PCR analysis, 21 differentially expressed genes were characterized, and among these, 10 genes (comprising three P450s, two glutathione S-transferases, one glycosyltransferase, two ATP-binding cassette transporters, one oxidase, and one hydrolase) exhibited constitutive upregulation in resistant plants. Our findings substantiated that increased herbicide metabolism is a driving force behind mesosulfuron-methyl resistance in this B. japonicus population.}, } @article {pmid38999371, year = {2024}, author = {Dell'Anna, G and Fanti, L and Fanizza, J and Barà, R and Barchi, A and Fasulo, E and Elmore, U and Rosati, R and Annese, V and Laterza, L and Fuccio, L and Azzolini, F and Danese, S and Mandarino, FV}, title = {VAC-Stent in the Treatment of Post-Esophagectomy Anastomotic Leaks: A New "Kid on the Block" Who Marries the Best of Old Techniques-A Review.}, journal = {Journal of clinical medicine}, volume = {13}, number = {13}, pages = {}, pmid = {38999371}, issn = {2077-0383}, abstract = {Esophagectomy, while a pivotal treatment for esophageal cancer, is not without adverse events. Among these, anastomotic leak (AL) is the most feared complication, threatening patient lives and incurring significant healthcare costs. The management of AL is complex and lacks standardization. Given the high morbidity and mortality rates associated with redo-surgery, which poses risks for already fragile patients, various endoscopic treatments have been developed over time. Self-expandable metallic stents (SEMSs) were the most widely used treatment until the early 2000s. The mechanism of action of SEMSs includes covering the wall defect, protecting it from secretions, and promoting healing. In 2010, endoscopic vacuum therapy (EVT) emerged as a viable alternative for treating ALs, quickly gaining acceptance in clinical practice. EVT involves placing a dedicated sponge under negative pressure inside or adjacent to the wall defect, aiming to clear the leak and promote granulation tissue formation. More recently, the VAC-Stent entered the scenario of endoscopic treatment of post-esophagectomy ALs. This device combines a fully covered SEMS with an integrated EVT sponge, blending the ability of SEMSs to exclude defects and maintain the patency of the esophageal lumen with the capacity of EVT to aspirate secretions and promote the formation of granulation tissue. Although the literature on this new device is not extensive, early results from the application of VAC-Stent have shown promising outcomes. This review aims to synthesize the preliminary efficacy and safety data on the device, thoroughly analyze its advantages over traditional techniques and disadvantages, explore areas for improvement, and propose future directions.}, } @article {pmid38997748, year = {2024}, author = {Kato, C and Ueda, K and Morimoto, S and Takahashi, S and Nakamura, S and Ozawa, F and Ito, D and Daté, Y and Okada, K and Kobayashi, N and Nakahara, J and Okano, H}, title = {Proteomic insights into extracellular vesicles in ALS for therapeutic potential of Ropinirole and biomarker discovery.}, journal = {Inflammation and regeneration}, volume = {44}, number = {1}, pages = {32}, pmid = {38997748}, issn = {1880-9693}, support = {JP21H05278//Japan Society for the Promotion of Science/ ; JP22K15736//Japan Society for the Promotion of Science/ ; JP22K07500//Japan Society for the Promotion of Science/ ; JP20H00485//Japan Society for the Promotion of Science/ ; JP22ek0109616//Japan Agency for Medical Research and Development/ ; JP23bm1123046//Japan Agency for Medical Research and Development/ ; JP23kk0305024//Japan Agency for Medical Research and Development/ ; JP21wm0425009//Japan Agency for Medical Research and Development/ ; JP22bm0804003//Japan Agency for Medical Research and Development/ ; JP22ek0109616//Japan Agency for Medical Research and Development/ ; JP23bm1423002//Japan Agency for Medical Research and Development/ ; }, abstract = {BACKGROUND: Extracellular vesicles (EVs) hold the potential for elucidating the pathogenesis of amyotrophic lateral sclerosis (ALS) and serve as biomarkers. Notably, the comparative and longitudinal alterations in the protein profiles of EVs in serum (sEVs) and cerebrospinal fluid (CSF; cEVs) of sporadic ALS (SALS) patients remain uncharted. Ropinirole hydrochloride (ROPI; dopamine D2 receptor [D2R] agonist), a new anti-ALS drug candidate identified through induced pluripotent stem cell (iPSC)-based drug discovery, has been suggested to inhibit ALS disease progression in the Ropinirole Hydrochloride Remedy for Amyotrophic Lateral Sclerosis (ROPALS) trial, but its mechanism of action is not well understood. Therefore, we tried to reveal longitudinal changes with disease progression and the effects of ROPI on protein profiles of EVs.

METHODS: We collected serum and CSF at fixed intervals from ten controls and from 20 SALS patients participating in the ROPALS trial. Comprehensive proteomic analysis of EVs, extracted from these samples, was conducted using liquid chromatography/mass spectrometer (LC/MS). Furthermore, we generated iPSC-derived astrocytes (iPasts) and performed RNA sequencing on astrocytes with or without ROPI treatment.

RESULTS: The findings revealed notable disparities yet high congruity in sEVs and cEVs protein profiles concerning disease status, time and ROPI administration. In SALS, both sEVs and cEVs presented elevated levels of inflammation-related proteins but reduced levels associated with unfolded protein response (UPR). These results mirrored the longitudinal changes after disease onset and correlated with the revised ALS Functional Rating Scale (ALSFRS-R) at sampling time, suggesting a link to the onset and progression of SALS. ROPI appeared to counteract these changes, attenuating inflammation-related protein levels and boosting those tied to UPR in SALS, proposing an anti-ALS impact on EV protein profiles. Reverse translational research using iPasts indicated that these changes may partly reflect the DRD2-dependent neuroinflammatory inhibitory effects of ROPI. We have also identified biomarkers that predict diagnosis and disease progression by machine learning-driven biomarker search.

CONCLUSIONS: Despite the limited sample size, this study pioneers in reporting time-series proteomic alterations in serum and CSF EVs from SALS patients, offering comprehensive insights into SALS pathogenesis, ROPI-induced changes, and potential prognostic and diagnostic biomarkers.}, } @article {pmid38997636, year = {2024}, author = {Karagianni, K and Dafou, D and Xanthopoulos, K and Sklaviadis, T and Kanata, E}, title = {RNA editing regulates glutamatergic synapses in the frontal cortex of a molecular subtype of Amyotrophic Lateral Sclerosis.}, journal = {Molecular medicine (Cambridge, Mass.)}, volume = {30}, number = {1}, pages = {101}, pmid = {38997636}, issn = {1528-3658}, support = {01146//Hellenic Foundation for Research and Innovation (H.F.R.I.) under the "2nd Call for H.F.R.I. Research Projects to support Post-Doctoral Researchers"/ ; 10829//Hellenic Foundation for Research and Innovation (H.F.R.I.) under the 4th Call for H.F.R.I. PhD Fellowships/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/genetics/metabolism ; *RNA Editing ; Humans ; *Frontal Lobe/metabolism ; *Synapses/metabolism/genetics ; Transcriptome ; Gene Expression Profiling ; Glutamic Acid/metabolism ; Computational Biology/methods ; Male ; Female ; Gene Expression Regulation ; Middle Aged ; }, abstract = {BACKGROUND: Amyotrophic Lateral Sclerosis (ALS) is a highly heterogenous neurodegenerative disorder that primarily affects upper and lower motor neurons, affecting additional cell types and brain regions. Underlying molecular mechanisms are still elusive, in part due to disease heterogeneity. Molecular disease subtyping through integrative analyses including RNA editing profiling is a novel approach for identification of molecular networks involved in pathogenesis.

METHODS: We aimed to highlight the role of RNA editing in ALS, focusing on the frontal cortex and the prevalent molecular disease subtype (ALS-Ox), previously determined by transcriptomic profile stratification. We established global RNA editing (editome) and gene expression (transcriptome) profiles in control and ALS-Ox cases, utilizing publicly available RNA-seq data (GSE153960) and an in-house analysis pipeline. Functional annotation and pathway analyses identified molecular processes affected by RNA editing alterations. Pearson correlation analyses assessed RNA editing effects on expression. Similar analyses on additional ALS-Ox and control samples (GSE124439) were performed for verification. Targeted re-sequencing and qRT-PCR analysis targeting CACNA1C, were performed using frontal cortex tissue from ALS and control samples (n = 3 samples/group).

RESULTS: We identified reduced global RNA editing in the frontal cortex of ALS-Ox cases. Differentially edited transcripts are enriched in synapses, particularly in the glutamatergic synapse pathway. Bioinformatic analyses on additional ALS-Ox and control RNA-seq data verified these findings. We identified increased recoding at the Q621R site in the GRIK2 transcript and determined positive correlations between RNA editing and gene expression alterations in ionotropic receptor subunits GRIA2, GRIA3 and the CACNA1C transcript, which encodes the pore forming subunit of a post-synaptic L-type calcium channel. Experimental data verified RNA editing alterations and editing-expression correlation in CACNA1C, highlighting CACNA1C as a target for further study.

CONCLUSIONS: We provide evidence on the involvement of RNA editing in the frontal cortex of an ALS molecular subtype, highlighting a modulatory role mediated though recoding and gene expression regulation on glutamatergic synapse related transcripts. We report RNA editing effects in disease-related transcripts and validated editing alterations in CACNA1C. Our study provides targets for further functional studies that could shed light in underlying disease mechanisms enabling novel therapeutic approaches.}, } @article {pmid38997630, year = {2024}, author = {Staderini, T and Bigi, A and Lagrève, C and Marzi, I and Bemporad, F and Chiti, F}, title = {Biophysical characterization of the phase separation of TDP-43 devoid of the C-terminal domain.}, journal = {Cellular & molecular biology letters}, volume = {29}, number = {1}, pages = {104}, pmid = {38997630}, issn = {1689-1392}, support = {AriSLA//Fondazione Italiana di Ricerca per la Sclerosi Laterale Amiotrofica/ ; project TDP-43-STRUCT//Fondazione Italiana di Ricerca per la Sclerosi Laterale Amiotrofica/ ; PRIN Project 2020PBS5MJ//Ministero dell'Università e della Ricerca/ ; Fondi di Ateneo 2021//Università degli studi di Firenze/ ; }, mesh = {*DNA-Binding Proteins/metabolism/chemistry ; Humans ; *Protein Domains ; Fluorescence Recovery After Photobleaching ; Phase Separation ; }, abstract = {BACKGROUND: Frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-TDP), amyotrophic lateral sclerosis (ALS) and limbic-predominant age-related TDP-43 encephalopathy (LATE) are associated with deposition of cytoplasmic inclusions of TAR DNA-binding protein 43 (TDP-43) in neurons. One complexity of this process lies in the ability of TDP-43 to form liquid-phase membraneless organelles in cells. Previous work has shown that the recombinant, purified, prion-like domain (PrLD) forms liquid droplets in vitro, but the behaviour of the complementary fragment is uncertain.

METHODS: We have purified such a construct without the PrLD (PrLD-less TDP-43) and have induced its phase separation using a solution-jump method and an array of biophysical techniques to study the morphology, state of matter and structure of the TDP-43 assemblies.

RESULTS: The fluorescent TMR-labelled protein construct, imaged using confocal fluorescence, formed rapidly (< 1 min) round, homogeneous and 0.5-1.0 µm wide assemblies which then coalesced into larger, yet round, species. When labelled with AlexaFluor488, they initially exhibited fluorescence recovery after photobleaching (FRAP), showing a liquid behaviour distinct from full-length TDP-43 and similar to PrLD. The protein molecules did not undergo major structural changes, as determined with circular dichroism and intrinsic fluorescence spectroscopies. This process had a pH and salt dependence distinct from those of full-length TDP-43 and its PrLD, which can be rationalized on the grounds of electrostatic forces.

CONCLUSIONS: Similarly to PrLD, PrLD-less TDP-43 forms liquid droplets in vitro through liquid-liquid phase separation (LLPS), unlike the full-length protein that rather undergoes liquid-solid phase separation (LSPS). These results offer a rationale of the complex electrostatic forces governing phase separation of full-length TDP-43 and its fragments. On the one hand, PrLD-less TDP-43 has a low pI and oppositively charged domains, and LLPS is inhibited by salts, which attenuate inter-domain electrostatic attractions. On the other hand, PrLD is positively charged due to a high isoionic point (pI) and LLPS is therefore promoted by salts and pH increases as they both reduce electrostatic repulsions. By contrast, full-length TDP-43 undergoes LSPS most favourably at its pI, with positive and negative salt dependences at lower and higher pH, respectively, depending on whether repulsive or attractive forces dominate, respectively.}, } @article {pmid38996790, year = {2024}, author = {Alqahtani, A and Alsubai, S and Sha, M and Dutta, AK and Zhang, YD}, title = {Intellectual assessment of amyotrophic lateral sclerosis using deep resemble forward neural network.}, journal = {Neural networks : the official journal of the International Neural Network Society}, volume = {178}, number = {}, pages = {106478}, doi = {10.1016/j.neunet.2024.106478}, pmid = {38996790}, issn = {1879-2782}, mesh = {*Amyotrophic Lateral Sclerosis/diagnosis/physiopathology/complications ; Humans ; *Neural Networks, Computer ; Deep Learning ; Algorithms ; Reproducibility of Results ; Machine Learning ; }, abstract = {ALS (Amyotrophic Lateral Sclerosis) is a neurodegenerative disorder causing profound physical disability that severely impairs a patient's life expectancy and quality of life. It also leads to muscular atrophy and progressive weakness of muscles due to insufficient nutrition in the body. At present, there are no disease-modifying therapies to cure ALS, and there is a lack of preventive tools. The general clinical assessments are based on symptom reports, neurophysiological tests, neurological examinations, and neuroimaging. But, these techniques possess various limitations of low reliability, lack of standardized protocols, and lack of sensitivity, especially in the early stages of disease. So, effective methods are required to detect the progression of the disease and minimize the suffering of patients. Extensive studies concentrated on investigating the causes of neurological disease, which creates a barrier to precise identification and classification of genes accompanied with ALS disease. Hence, the proposed system implements a deep RSFFNNCNN (Resemble Single Feed Forward Neural Network-Convolutional Neural Network) algorithm to effectively classify the clinical associations of ALS. It involves the addition of custom weights to the kernel initializer and neutralizer 'k' parameter to each hidden layer in the network. This is done to increase the stability and learning ability of the classifier. Additionally, the comparison of the proposed approach is performed with SFNN (Single Feed NN) and ML (Machine Learning) based algorithms, namely, NB (Naïve Bayes), XGBoost (Extreme Gradient Boosting) and RF (Random Forest), to estimate the efficacy of the proposed model. The reliability of the proposed algorithm is measured by deploying performance metrics such as precision, recall, F1 score, and accuracy.}, } @article {pmid38996764, year = {2024}, author = {Montero, AS and Aliouat, I and Ribon, M and Canney, M and Goldwirt, L and Mourah, S and Berriat, F and Lobsiger, CS and Pradat, PF and Salachas, F and Bruneteau, G and Carpentier, A and Boillée, S}, title = {Effect of ultrasound-mediated blood-spinal cord barrier opening on survival and motor function in females in an amyotrophic lateral sclerosis mouse model.}, journal = {EBioMedicine}, volume = {106}, number = {}, pages = {105235}, pmid = {38996764}, issn = {2352-3964}, mesh = {Animals ; *Amyotrophic Lateral Sclerosis/metabolism/therapy ; Female ; *Disease Models, Animal ; Mice ; *Spinal Cord/metabolism ; *Blood-Brain Barrier/metabolism ; *Insulin-Like Growth Factor I/metabolism ; Mice, Transgenic ; Humans ; Motor Neurons/metabolism ; Ultrasonic Waves ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by a progressive loss of motor neurons. The limited efficacy of recent therapies in clinical development may be linked to lack of drug penetration to the affected motor neurons due to the blood-brain barrier (BBB) and blood-spinal cord barrier (BSCB).

METHODS: In this work, the safety and efficacy of repeated short transient opening of the BSCB by low intensity pulsed ultrasound (US, sonication) was studied in females of an ALS mouse model (B6.Cg-Tg(SOD1∗G93A)1Gur/J). The BSCB was disrupted using a 1 MHz ultrasound transducer coupled to the spinal cord, with and without injection of insulin-like growth factor 1 (IGF1), a neurotrophic factor that has previously shown efficacy in ALS models.

FINDINGS: Results in wild-type (WT) animals demonstrated that the BSCB can be safely disrupted and IGF1 concentrations significantly enhanced after a single session of transient BSCB disruption (176 ± 32 μg/g vs. 0.16 ± 0.008 μg/g, p < 0.0001). Five repeated weekly US sessions performed in female ALS mice demonstrated a survival advantage in mice treated with IGF1 and US (US IGF1) compared to treatment with IGF1 alone (176 vs. 166 days, p = 0.0038). Surprisingly, this survival advantage was also present in mice treated with US alone vs. untreated mice (178.5 vs. 166.5 days, p = 0.0061). Muscle strength did not show difference among the groups. Analysis of glial cell immunoreactivity and microglial transcriptome showing reduced cell proliferation pathways, in addition to lymphocyte infiltration, suggested that the beneficial effect of US or US IGF1 could act through immune cell modulation.

INTERPRETATION: These results show the first step towards a possible beneficial impact of transient BSCB opening for ALS therapy and suggest implication of immune cells.

FUNDING: Fondation pour la Recherche Médicale (FRM). Investissements d'avenirANR-10-IAIHU-06, Société Française de Neurochirurgie (SFNC), Fond d'étude et de Recherche du Corps Medical (FERCM), Aide à la Recherche des Maladies du Cerveau (ARMC), SLA Fondation Recherche (SLAFR), French Ministry for High Education and Research (MENR), Carthera, Laboratoire de Recherche en Technologies Chirurgicales Avancées (LRTCA).}, } @article {pmid38996643, year = {2024}, author = {Sheehan, Y and Cochrane, A and Treloar, C and Grebely, J and Tedla, N and Lloyd, AR and Lafferty, L}, title = {Understanding hepatitis C virus (HCV) health literacy and educational needs among people in prison to enhance HCV care in prisons.}, journal = {The International journal on drug policy}, volume = {130}, number = {}, pages = {104516}, doi = {10.1016/j.drugpo.2024.104516}, pmid = {38996643}, issn = {1873-4758}, mesh = {Humans ; Male ; *Health Literacy ; *Hepatitis C ; *Prisoners/psychology ; Adult ; Australia ; *Prisons ; Middle Aged ; Health Knowledge, Attitudes, Practice ; Substance Abuse, Intravenous ; }, abstract = {BACKGROUND: Hepatitis C virus (HCV) is a significant concern within prison populations. Provision of HCV testing and treatment for people in prison is expanding and a key component of global elimination efforts. Despite growing service availability, several challenges remain in HCV testing and treatment engagement during incarceration. The PIVOT study demonstrated that a 'one-stop-shop' intervention (point-of-care HCV RNA testing, Fibroscan®, nurse-led clinical assessment, and fast-tracked direct-acting antiviral prescription) enhanced HCV testing and treatment at a reception prison in Australia. Utilising Squier et al's Health Literacy Skills Framework, this analysis aimed to understand HCV health literacy and educational needs among people at a reception prison in Australia.

METHODS: Semi-structured interviews were conducted with twenty-four male PIVOT study participants. Purposive sampling ensured comparable representation of those with: 1) prior HCV testing history (standard pathology / no prior testing), and 2) injecting drug use history (IDU; ever / never).

RESULTS: Varied HCV health literacy levels and educational needs were evident amongst people in prison. Whilst those with multiple incarceration episodes and IDU history (prior knowledge) appeared to have stronger HCV health literacy than those without, substantial gaps in HCV health literacy were evident. Knowledge of HCV transmission risks in prison was high, and most understood the importance of HCV testing and treatment in prison (comprehension), but ability to engage with HCV testing and treatment services, participation in safe injecting behaviours (health-related behaviours), and knowledge of re-infection and re-treatment, within the context of the prison environment, were suboptimal. There was a general desire for increased HCV education in prison.

CONCLUSION: Gaps in HCV health literacy among people in prison were evident, indicating opportunities for improvement. A targeted HCV education program for people in prison, addressing the gaps identified in this analysis, may enhance HCV testing, treatment, and prevention by fostering stronger HCV health literacy among people in prison.}, } @article {pmid38995133, year = {2024}, author = {Bacigalupo, I and Finocchietti, M and Paoletti, O and Bargagli, AM and Brunori, P and Lombardi, N and Sciancalepore, F and Agabiti, N and Kirchmayer, U}, title = {Incidence and prevalence of Amyotrophic Lateral Sclerosis in three Italian Regions: a study based on health administrative databases.}, journal = {Epidemiologia e prevenzione}, volume = {48}, number = {3}, pages = {201-209}, doi = {10.19191/EP24.3.A710.055}, pmid = {38995133}, issn = {1120-9763}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/epidemiology ; Italy/epidemiology ; Incidence ; Prevalence ; Male ; Aged ; Female ; Retrospective Studies ; Middle Aged ; Adult ; Databases, Factual ; Aged, 80 and over ; Sex Distribution ; Adolescent ; Archives ; Algorithms ; Young Adult ; Age Distribution ; }, abstract = {OBJECTIVES: to estimate Amyotrophic Lateral Sclerosis (ALS) incidence and prevalence in three Italian Regions (Lazio, Tuscany, and Umbria), using health administrative databases.

DESIGN: retrospective population-based study.

SETTING AND PARTICIPANTS: ALS patients residing in Lazio, Umbria, and Tuscany were identified through an algorithm based on three different administrative databases: hospital discharge records, exemptions from health care co-payment, and emergency departments (study period 2014-2019). Crude, age- and gender-specific prevalence were calculated on 31.12.2019 and incidence rates of ALS were standardised by region, year, and gender between 2014-2019. Using a clinical dataset available in the Lazio Region, the proportion of individuals residing in the region correctly identified as ALS cases by the algorithm were calculated.

MAIN OUTCOMES MEASURES: prevalence and incidence rates.

RESULTS: a total of 1,031 ALS patients (>=18 years) were identified: 408 cases in Tuscany, 546 in Lazio, and 77 in Umbria. ALS standardised prevalence (per 100,000) was similar among regions: 12.31 in Tuscany, 11.52 in Lazio, and 9.90 in Umbria. The 5-year crude rates were higher in men, and in people aged 65-79 years. Among 310 patients included in the clinical dataset, 263 (84.8%) were correctly identified by the algorithm based on health administrative databases.

CONCLUSIONS: ALS prevalence and incidence in three Central Italy Regions are rather similar, but slightly higher than those previously reported. This finding is plausible, given that previous results relate to at least ten years ago and evidenced increasing trends. Overall, the results of this paper encourage the use of administrative data to produce occurrence estimates, useful to both epidemiological surveillance and research and healthcare policies.}, } @article {pmid38992244, year = {2024}, author = {Hunt von Herbing, I}, title = {Energetic Costs of Stress in Developing Fishes: Quantifying Allostasis and Allostatic Load.}, journal = {Integrative and comparative biology}, volume = {64}, number = {3}, pages = {1019-1033}, doi = {10.1093/icb/icae094}, pmid = {38992244}, issn = {1557-7023}, support = {GP64231//University of North Texas/ ; }, mesh = {Animals ; *Zebrafish/physiology/growth & development ; *Allostasis/physiology ; *Energy Metabolism ; *Stress, Physiological ; Larva/growth & development/physiology ; Yolk Sac/physiology ; Hypoxia ; }, abstract = {Stress exerts negative effects on fish health through stimulation of the hypothalamic-pituitary-interrenal axis and autonomic nervous system, resulting in heightened neural and neuroendocrine responses. Energetic investment and physiological adaptation are then required to re-establish homeostatic stability or reach a new allostatic state. The cost of the energetic investment is referred to as allostatic load (AL). While determining the sources of stress and assessing their consequences have resulted in estimates of AL, most of this work has been conducted in adult mammals and humans; no ALs exist for developing fish. From a series of experiments on a model species, zebrafish (Danio rerio), whose yolk-sac larvae were exposed to two chronic stressors (high-temperature and hypoxia), ALs were quantified based on biomarkers of ontogenetic changes in growth, morphometrics, and metabolic activities. Results showed that for zebrafish yolk-sac larvae, chronic stress imposed high AL and, thus, high total allostatic energetic costs, (Rt (AL)), because of prolonged energy demand in the face of limited resources (e.g., yolk). Under severe chronic stress, energetic costs were sufficiently large that energy-limited developing fish may not be able to fully compensate, resulting in maladaptive responses from allostatic overload, leading either to death or to novel allostatic states, possibly more resilient to environmental change.}, } @article {pmid38991324, year = {2024}, author = {Reis, J and Spencer, PS}, title = {An introduction to environmental neurotoxicology: Lessons from a clinical perspective.}, journal = {Journal of the neurological sciences}, volume = {463}, number = {}, pages = {123108}, doi = {10.1016/j.jns.2024.123108}, pmid = {38991324}, issn = {1878-5883}, mesh = {Humans ; *Environmental Exposure/adverse effects ; *Neurotoxicity Syndromes/etiology ; Animals ; }, abstract = {In 1992, the Committee on Neurotoxicology and Models for Assessing Risk of the National Academy of Sciences in Washington DC focused with a scientific perspective on the identification of substances with neurotoxic potential, studies of exposed populations, risk assessment, and biologic markers of disease. This Committee recommended: "all physicians should be trained to take a thorough occupational-exposure history and to be aware of other possible sources of toxic exposure". Although convened after several outbreaks of neurotoxic syndromes, clinical neurological considerations were lacking. After defining keys words, namely Environment, Neurotoxicology and Neurotoxicants, we present some demonstrative cases; e.g., the Epidemic Neuropathy in Cuba, Minamata disease, ALS/PDC on Guam, and the ALS hot spot in the French Alps. Always with a clinical and practical approach, we will then review the milieux that contain and convey potential neurotoxicants, the different exposure routes and the clinical presentations. Drawing lessons from clinical cases, we offer some thoughts concerning the future of Environmental Neurotoxicology (ENT). Pointing notably to the diffuse chemical contamination of ecosystems and living beings, including Homo sapiens, we question the real impact of agents with neurotoxic potential on the human brain, considering the effects, for example, of air pollution, endocrine disruptors and nanoparticles. Concern is expressed over the lack of knowledge of the non-monotonic kinetics of many of these chemicals, the major concern being related to mixtures and low-dose exposures, as well as the delayed appearance in clinical expression of prevalent neurodegenerative diseases.}, } @article {pmid38991167, year = {2024}, author = {Cave, R}, title = {How People Living With Amyotrophic Lateral Sclerosis Use Personalized Automatic Speech Recognition Technology to Support Communication.}, journal = {Journal of speech, language, and hearing research : JSLHR}, volume = {67}, number = {11}, pages = {4186-4202}, doi = {10.1044/2024_JSLHR-24-00097}, pmid = {38991167}, issn = {1558-9102}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/psychology/complications ; *Speech Recognition Software ; Male ; Female ; *Dysarthria/etiology/psychology/rehabilitation ; Middle Aged ; Aged ; Communication ; Communication Devices for People with Disabilities ; }, abstract = {PURPOSE: Amyotrophic lateral sclerosis (ALS) is a progressive, ultimately fatal disease causing progressive muscular weakness. Most people living with ALS (plwALS) experience dysarthria, eventually becoming unable to communicate using natural speech. Many wish to use speech for as long as possible. Personalized automated speech recognition (ASR) model technology, such as Google's Project Relate, is argued to better recognize speech with dysarthria, supporting maintenance of understanding through real-time captioning. The objectives of this study are how plwALS and communication partners use Relate in everyday conversation over a period of up to 12 months and how it may change with any decline in speech over time.

METHOD: This study videoed interactions between three plwALS and communication partners. We assessed ASR caption accuracy and how well they preserved meaning. Conversation analysis was used to identify participants' own organizational practices in the accomplishment of interaction. Thematic analysis was used to understand better the participants' experiences of using ASR captions.

RESULTS: All plwALS reported lower-than-expected ASR accuracy when used in conversation and felt ASR captioning was only useful in certain contexts. All participants liked the concept of live captioning and were hopeful that future improvements to ASR accuracy may support their communication in everyday life.

CONCLUSIONS: Training is needed on best practices for customization and practical use of ASR technology and for the limitations of ASR in conversational settings. Support is needed for those less confident with technology and to reduce misplaced allocation of ownership of captioning errors, risking negative effects on psychological well-being.}, } @article {pmid38990927, year = {2024}, author = {Srinivasan, V and Homer, V and Barton, D and Clutterbuck-James, A and Jenkins, S and Potter, C and Brock, K and Logan, A and Smith, D and Bruce, L and Nagy, Z and Bach, SP}, title = {A low molecular weight dextran sulphate, ILB®, for the treatment of amyotrophic lateral sclerosis (ALS): An open-label, single-arm, single-centre, phase II trial.}, journal = {PloS one}, volume = {19}, number = {7}, pages = {e0291285}, pmid = {38990927}, issn = {1932-6203}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy ; Male ; Female ; Middle Aged ; Aged ; Prospective Studies ; Treatment Outcome ; Adult ; Neuroprotective Agents/therapeutic use/administration & dosage/adverse effects ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig´s disease, is a rare neurological condition and is the most common motor neurone disease. It is a fatal disease with specific loss of motor neurons in the spinal cord, brain stem, and motor cortex leading to progressive paralysis and usually death within five years of diagnosis. There remains no cure for ALS, and management is focused on a combination of neuroprotective medication, respiratory support, and management by multidisciplinary clinics.

PATIENTS AND METHODS: This prospective, single-arm, open-label phase II clinical trial of sustained weekly administration of 2 mg/kg ILB® (a low-molecular weight dextran sulphate) was conducted in a single UK hospital. Eligible patients were at least 18 years and had a definite diagnosis of ALS according to El Escorial Criteria. The co-primary outcomes were safety, tolerability, and quantity of ILB® administered. EudraCT number. 2018-000668-28.

FINDINGS: Between 18-Apr-2019 and 27-Mar-2020, 11 patients were recruited and treated for up to 38 weeks. There were no treatment terminations or withdrawals. One serious adverse event was reported, which was not related to ILB® and resolved without sequalae. 270 mild/moderate adverse events were reported with no intolerable events occurring during the trial. The total number of ILB® treatments administered per patient ranged from 4 to 38, with a cumulative dose ranging from 745 to 6668 mg. As a result of the COVID-19 pandemic and the high-risk status of study participants, recruitment and treatment was suspended early in Mar-2020. At the long-term follow-up, three patients had died after the trial was halted, between 53 and 62 weeks after their final ILB® injection.

INTERPRETATION: Long-term weekly ILB® injections of 2 mg/kg was well tolerated and had an acceptable safety profile in patients with ALS.

TRIAL REGISTRATION: EudraCT: 2018-000668-28. clinicaltrials.gov: NCT03705390. This trial adheres to the principles of GCP in the design, conduct, recording and reporting of clinical trials as listed in part 2, "Conditions and Principles which apply to all Clinical Trials" under the header "Principles based on Articles 2 to 5 of the EU GCP Directive" in the Medicines for Human Use Clinical Trials Regulations (as amended in SI 2006/1928). For clarity, the study did not conform to all aspects of the International Conference on Harmonisation (ICH) E6 R2 Guidelines for GCP (also known as 'ICH GCP'). Of note, we did not use an external database, perform 100% source data verification, and only primary outcome data were analysed in parallel by a second, independent statistician.}, } @article {pmid38990842, year = {2024}, author = {Yip, PK and Pizzasegola, C and Gladman, S and Biggio, ML and Marino, M and Jayasinghe, M and Ullah, F and Dyall, SC and Malaspina, A and Bendotti, C and Michael-Titus, A}, title = {Correction: The Omega-3 Fatty Acid Eicosapentaenoic Acid Accelerates Disease Progression in a Model of Amyotrophic Lateral Sclerosis.}, journal = {PloS one}, volume = {19}, number = {7}, pages = {e0307246}, pmid = {38990842}, issn = {1932-6203}, abstract = {[This corrects the article DOI: 10.1371/journal.pone.0061626.].}, } @article {pmid38989937, year = {2025}, author = {Locatelli, M and Farina, C}, title = {Role of copper in central nervous system physiology and pathology.}, journal = {Neural regeneration research}, volume = {20}, number = {4}, pages = {1058-1068}, pmid = {38989937}, issn = {1673-5374}, abstract = {Copper is a transition metal and an essential element for the organism, as alterations in its homeostasis leading to metal accumulation or deficiency have pathological effects in several organs, including the central nervous system. Central copper dysregulations have been evidenced in two genetic disorders characterized by mutations in the copper-ATPases ATP7A and ATP7B, Menkes disease and Wilson's disease, respectively, and also in multifactorial neurological disorders such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and multiple sclerosis. This review summarizes current knowledge about the role of copper in central nervous system physiology and pathology, reports about unbalances in copper levels and/or distribution under disease, describes relevant animal models for human disorders where copper metabolism genes are dysregulated, and discusses relevant therapeutic approaches modulating copper availability. Overall, alterations in copper metabolism may contribute to the etiology of central nervous system disorders and represent relevant therapeutic targets to restore tissue homeostasis.}, } @article {pmid38989900, year = {2025}, author = {Marchica, V and Biasetti, L and Barnard, J and Li, S and Nikolaou, N and Frosch, MP and Lucente, DE and Eldaief, M and King, A and Fanto, M and Troakes, C and Houart, C and Smith, BN}, title = {Annexin A11 mutations are associated with nuclear envelope dysfunction in vivo and in human tissues.}, journal = {Brain : a journal of neurology}, volume = {148}, number = {1}, pages = {276-290}, pmid = {38989900}, issn = {1460-2156}, support = {//Motor Neurone Disease Association UK/ ; /MRF/MRF/United Kingdom ; //Van Geest Foundation/ ; //MNDA Studentship/ ; //Project Grants/ ; 855-791//Project Grant by the MNDA/ ; }, mesh = {Animals ; Humans ; *Amyotrophic Lateral Sclerosis/genetics/pathology ; *Zebrafish ; *Nuclear Envelope/metabolism/genetics ; *Mutation ; *Annexins/genetics/metabolism ; Lamin Type B/genetics/metabolism ; Frontotemporal Dementia/genetics/pathology ; Male ; Spinal Cord/metabolism/pathology ; }, abstract = {Annexin A11 mutations are a rare cause of amyotrophic lateral sclerosis (ALS), wherein replicated protein variants P36R, G38R, D40G and D40Y are located in a small helix within the long, disordered N-terminus. To elucidate disease mechanisms, we characterized the phenotypes induced by a genetic loss-of-function and by misexpression of G38R and D40G in vivo. Loss of Annexin A11 results in a low-penetrant behavioural phenotype and aberrant axonal morphology in zebrafish homozygous knockout larvae, which is rescued by human wild-type Annexin A11. Both Annexin A11 knockout/down and ALS variants trigger nuclear dysfunction characterized by Lamin B2 mislocalization. The Lamin B2 signature also presented in anterior horn, spinal cord neurons from post-mortem ALS ± frontotemporal dementia patient tissue possessing G38R and D40G protein variants. These findings suggest mutant Annexin A11 acts as a dominant negative, revealing a potential early nucleopathy highlighting nuclear envelope abnormalities preceding behavioural abnormality in animal models.}, } @article {pmid38989463, year = {2024}, author = {Pasternack, N and Doucet-O'Hare, T and Johnson, K and , and Paulsen, O and Nath, A}, title = {Endogenous retroviruses are dysregulated in ALS.}, journal = {iScience}, volume = {27}, number = {7}, pages = {110147}, pmid = {38989463}, issn = {2589-0042}, abstract = {Amyotrophic lateral sclerosis (ALS) is a universally fatal neurodegenerative disease with no cure. Human endogenous retroviruses (HERVs) have been implicated in its pathogenesis but their relevance to ALS is not fully understood. We examined bulk RNA-seq data from almost 2,000 ALS and unaffected control samples derived from the cortex and spinal cord. Using different methods of feature selection, including differential expression analysis and machine learning, we discovered that transcription of HERV-K loci 1q22 and 8p23.1 were significantly upregulated in the spinal cord of individuals with ALS. Additionally, we identified a subset of ALS patients with upregulated HERV-K expression in the cortex and spinal cord. We also found the expression of HERV-K loci 19q11 and 8p23.1 was correlated with protein coding genes previously implicated in ALS and dysregulated in ALS patients in this study. These results clarify the association of HERV-K and ALS and highlight specific genes in the pathobiology of late-stage ALS.}, } @article {pmid38988889, year = {2024}, author = {Ansari, U and Alam, M and Nadora, D and Muttalib, Z and Chen, V and Taguinod, I and FitzPatrick, M and Wen, J and Ansari, Z and Lui, F}, title = {Assessing the efficacy of amyotrophic lateral sclerosis drugs in slowing disease progression: A literature review.}, journal = {AIMS neuroscience}, volume = {11}, number = {2}, pages = {166-177}, pmid = {38988889}, issn = {2373-7972}, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal and intricate neurodegenerative disease that impacts upper and lower motor neurons within the central nervous system, leading to their progressive destruction. Despite extensive research, the pathogenesis of this multifaceted disease remains elusive. The United States Food and Drug Administration (FDA) has granted approval for seven medications designed to address ALS and mitigate its associated symptoms. These FDA-sanctioned treatments are Qalsody, Relyvrio, Radicava, Rilutek, Tiglutik, Exservan, and Nuedexta. In this review, the effects of these seven drugs on ALS based on their mechanism of action, dosing, and clinical presentations are comprehensively summarized. Each medication offers a distinct approach to manage ALS, aiming to alleviate the burdensome symptoms and slow the disease's progression, thereby improving the quality of life for individuals affected by this neurological condition. However, despite these advancements in pharmaceutical interventions, finding a definitive cure for ALS remains a significant challenge. Continuous investigation into ALS pathophysiology and therapeutic avenues remains imperative, necessitating further research collaborations and innovative approaches to unravel the complex mechanisms underlying this debilitating condition.}, } @article {pmid38988205, year = {2024}, author = {Arnaldi, P and Casarotto, E and Relucenti, M and Bellese, G and Gagliani, MC and Crippa, V and Castagnola, P and Cortese, K}, title = {A NSC-34 cell line-derived spheroid model: Potential and challenges for in vitro evaluation of neurodegeneration.}, journal = {Microscopy research and technique}, volume = {87}, number = {11}, pages = {2785-2800}, doi = {10.1002/jemt.24651}, pmid = {38988205}, issn = {1097-0029}, support = {PRIN2020PBS5MJ//Ministero dell'Università e della Ricerca/ ; PRIN2022KSJZF5//Ministero dell'Università e della Ricerca/ ; //University of Genoa/ ; 100008-2022-KC-FRA_ANATOMIA//Fondi Ricerca Ateneo/ ; //Italian Ministry of Health (Ricerca Corrente)/ ; }, mesh = {*Spheroids, Cellular/pathology ; Animals ; Mice ; *DNA-Binding Proteins/metabolism ; *Amyotrophic Lateral Sclerosis/pathology/metabolism ; Cell Line ; Motor Neurons/pathology ; Cell Survival ; Neurodegenerative Diseases/pathology ; Cell Culture Techniques/methods ; Spinal Cord/cytology/pathology ; Hydrogels/chemistry ; Humans ; Mitochondria/metabolism ; }, abstract = {Three-dimensional (3D) spheroid models aim to bridge the gap between traditional two-dimensional (2D) cultures and the complex in vivo tissue environment. These models, created by self-clustering cells to mimic a 3D environment with surrounding extracellular framework, provide a valuable research tool. The NSC-34 cell line, generated by fusing mouse spinal cord motor neurons and neuroblastoma cells, is essential for studying neurodegenerative diseases like amyotrophic lateral sclerosis (ALS), where abnormal protein accumulation, such as TAR-DNA-binding protein 43 (TDP-43), occurs in affected nerve cells. However, NSC-34 behavior in a 3D context remains underexplored, and this study represents the first attempt to create a 3D model to determine its suitability for studying pathology. We generated NSC-34 spheroids using a nonadhesive hydrogel-based template and characterized them for 6 days. Light microscopy revealed that NSC-34 cells in 3D maintained high viability, a distinct round shape, and forming stable membrane connections. Scanning electron microscopy identified multiple tunnel-like structures, while ultrastructural analysis highlighted nuclear bending and mitochondria alterations. Using inducible GFP-TDP-43-expressing NSC-34 spheroids, we explored whether 3D structure affected TDP-43 expression, localization, and aggregation. Spheroids displayed nuclear GFP-TDP-43 expression, albeit at a reduced level compared with 2D cultures and generated both TDP-35 fragments and TDP-43 aggregates. This study sheds light on the distinctive behavior of NSC-34 in 3D culture, suggesting caution in the use of the 3D model for ALS or TDP-43 pathologies. Yet, it underscores the spheroids' potential for investigating fundamental cellular mechanisms, cell adaptation in a 3D context, future bioreactor applications, and drug penetration studies. RESEARCH HIGHLIGHTS: 3D spheroid generation: NSC-34 spheroids, developed using a hydrogel-based template, showed high viability and distinct shapes for 6 days. Structural features: advanced microscopy identified tunnel-like structures and nuclear and mitochondrial changes in the spheroids. Protein dynamics: the study observed how 3D structures impact TDP-43 behavior, with altered expression but similar aggregation patterns to 2D cultures. Research implications: this study reveals the unique behavior of NSC-34 in 3D culture, suggests a careful approach to use this model for ALS or TDP-43 pathologies, and highlights its potential in cellular mechanism research and drug testing applications.}, } @article {pmid38988008, year = {2025}, author = {Murakami, A and Koga, S and Fujioka, S and White, AE and Bieniek, KF and Sekiya, H and DeJesus-Hernandez, M and Finch, NA and van Blitterswijk, M and Nakamura, M and Tsuboi, Y and Murray, ME and Wszolek, ZK and Dickson, DW}, title = {Upper motor neuron-predominant motor neuron disease presenting as atypical parkinsonism: A clinicopathological study.}, journal = {Brain pathology (Zurich, Switzerland)}, volume = {35}, number = {1}, pages = {e13286}, pmid = {38988008}, issn = {1750-3639}, support = {P01-AG03949/GF/NIH HHS/United States ; R01-AG062348/GF/NIH HHS/United States ; 1U19AG063911/GF/NIH HHS/United States ; P30-AG062677/GF/NIH HHS/United States ; FAIN: U19AG063911/GF/NIH HHS/United States ; P30 AG062677/AG/NIA NIH HHS/United States ; R01-NS121125/GF/NIH HHS/United States ; P01 AG003949/AG/NIA NIH HHS/United States ; RF1-NS123052/GF/NIH HHS/United States ; RF1 NS123052/NS/NINDS NIH HHS/United States ; R01 NS121125/NS/NINDS NIH HHS/United States ; U54 NS100693/NS/NINDS NIH HHS/United States ; U19 AG063911/AG/NIA NIH HHS/United States ; U54-NS100693/GF/NIH HHS/United States ; }, mesh = {Humans ; Male ; Female ; Aged ; Middle Aged ; *Motor Neuron Disease/pathology/diagnosis ; *Parkinsonian Disorders/pathology/diagnosis ; Aged, 80 and over ; Motor Neurons/pathology ; Amyotrophic Lateral Sclerosis/pathology/diagnosis ; Supranuclear Palsy, Progressive/pathology/diagnosis ; DNA-Binding Proteins/metabolism ; Corticobasal Degeneration/pathology/diagnosis ; Diagnosis, Differential ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by upper and lower motor neuron signs. There are, however, cases where upper motor neurons (UMNs) are predominantly affected, leading to clinical presentations of UMN-dominant ALS or primary lateral sclerosis. Furthermore, cases exhibiting an UMN-predominant pattern of motor neuron disease (MND) presenting with corticobasal syndrome (CBS) have been sparsely reported. This study aims to clarify the clinicopathological features of patients with UMN-predominant MND. We reviewed 24 patients with UMN-predominant MND with TDP-43 pathology in the presence or absence of frontotemporal lobar degeneration. Additionally, we reviewed the medical records of patients with pathologically-confirmed corticobasal degeneration (CBD) who received a final clinical diagnosis of CBS (n = 10) and patients with pathologically-confirmed progressive supranuclear palsy (PSP) who received a final clinical diagnosis of PSP syndrome (n = 10). Of 24 UMN-predominant MND patients, 20 had a clinical diagnosis of an atypical parkinsonian disorder, including CBS (n = 11) and PSP syndrome (n = 8). Only two patients had antemortem diagnoses of motor neuron disease. UMN-predominant MND patients with CBS less frequently exhibited apraxia than those with CBD, and they were less likely to meet clinical criteria for possible or probable CBS. Similarly, UMN-predominant MND patients with PSP syndrome less often met clinical criteria for probable PSP than PSP patients with PSP syndrome. Our findings suggest that UMN-predominant MND can mimic atypical parkinsonism, and should be considered in the differential diagnosis of CBS and PSP syndrome, in particular when criteria are not met.}, } @article {pmid38987905, year = {2024}, author = {Bergem, AK and Aamotsmo, T}, title = {Navigating parenthood in the face of amyotrophic lateral sclerosis: A qualitative exploration of partner experiences.}, journal = {Scandinavian journal of caring sciences}, volume = {38}, number = {4}, pages = {835-843}, doi = {10.1111/scs.13282}, pmid = {38987905}, issn = {1471-6712}, mesh = {Humans ; Male ; Female ; *Amyotrophic Lateral Sclerosis/psychology ; *Qualitative Research ; Adult ; Norway ; *Adaptation, Psychological ; Middle Aged ; *Parents/psychology ; Aged ; Child ; }, abstract = {INTRODUCTION: Among people diagnosed with Amyotrophic Lateral Sclerosis (ALS), there are parents with children living at home. Children in families experiencing severe illness are exposed to stress and health risks. Since 2010, healthcare personnel in Norway must assess whether patients have children under 18 years of age and make sure the children's needs for support are met. A child's ability to cope with family life affected by a serious illness depends on how the parent without the disease manages the situation. Little is known about how the partner of someone affected by ALS manages being next of kin and a parent simultaneously, and what kind of support they need.

METHODS: During 2021-2022, six semi-structured interviews were conducted with partners to persons with ALS, whom had children living at home. The interviews were transcribed verbatim and analysed through qualitative content analysis.

RESULTS: Three themes with subthemes emerged: (1) Together, yet alone; (a) restricted home life, (b) missing the sharing of responsibilities and tasks as equal parents, and (c) caught between children's and partner's needs; (2) Experience of coping while waiting for death; (a) cherishing the moments, (b) sense of coping and concern, and (c) ensuring to get recharged; and (3) Support in times of need; (a) difficult to ask the network for help and (b) the healthcare system does not see the whole family.

CONCLUSIONS: Our respondents felt alone, caught between the needs of their children and partner, without necessary support from the services, and were left to handle everyday life with all new challenges on their own. Future healthcare services need to consider the challenges faced by families dealing with life-limiting illnesses. A family-focused perspective is needed, so is peer support and interventions that address both emotional and practical aspects of life with an ill partner.}, } @article {pmid38987226, year = {2024}, author = {Luo, X and Heydari, A and Renfrey, D and Gardner, Z and He, S and Tang, Y and Weiss, GA and Rogers, ML and Raston, CL}, title = {Sustainability-Driven Accelerated Shear-Mediated Immunoassay for Amyotrophic Lateral Sclerosis Detection.}, journal = {ChemSusChem}, volume = {17}, number = {21}, pages = {e202401008}, doi = {10.1002/cssc.202401008}, pmid = {38987226}, issn = {1864-564X}, support = {DP200101106//Australian Research Council/ ; IC190100034//Australian Research Council/ ; //Flinders Health Seed Foundation/ ; //Australian Nanotechnology Network/ ; //Flinders University Research Investment Fund/ ; //Australian Microscopy and Microanalysis Research Facility/ ; //Australian National Fabrication Facility (ANFF)/ ; }, mesh = {*Amyotrophic Lateral Sclerosis ; Humans ; Immunoassay/methods ; Limit of Detection ; Biomarkers ; }, abstract = {Healthcare facilities produce millions of tons of waste annually, with a significant portion consisting of diagnostic plasticware. Here, we introduce a new detection platform that completely replaces traditional assay plates with a piece of membrane, offering a much greener and more sustainable alternative. The membrane, integrated within the portable vortex fluidic device (P-VFD), enables rapid detection of a clinically relevant protein biomarker, urinary p75[ECD]. This biomarker is utilized to evaluate the prognosis, disease severity, and progression of amyotrophic lateral sclerosis (ALS). This assay has a limit-of-detection (LOD) of 4.03 pg, which is comparable to the plate-based assay (2.24 pg) and has been optimised through a full factorial design of experiments (DOE) and response surface methodology (RSM). P-VFD has great potential in quantifying p75[ECD] in human biofluids and can significantly reduce the assay time to 5 min compared to the current plate-based p75[ECD] ELISA assay (3 days), with at least a 4.4-fold reduction in the usage of the detection antibody.}, } @article {pmid38986433, year = {2025}, author = {Rifai, OM and Waldron, FM and Sleibi, D and O'Shaughnessy, J and Leighton, DJ and Gregory, JM}, title = {Clinicopathological analysis of NEK1 variants in amyotrophic lateral sclerosis.}, journal = {Brain pathology (Zurich, Switzerland)}, volume = {35}, number = {1}, pages = {e13287}, pmid = {38986433}, issn = {1750-3639}, support = {108890/Z/15/Z/WT_/Wellcome Trust/United Kingdom ; R01 NS127186/NS/NINDS NIH HHS/United States ; 1R01NS127186/NS/NINDS NIH HHS/United States ; /WT_/Wellcome Trust/United Kingdom ; BB-2022-C4-L2//Target ALS/ ; }, mesh = {Humans ; *NIMA-Related Kinase 1/genetics ; *Amyotrophic Lateral Sclerosis/genetics/pathology ; Male ; Female ; Middle Aged ; Aged ; DNA-Binding Proteins/genetics/metabolism ; Mutation ; Mutation, Missense ; Adult ; }, abstract = {Many genes have been linked to amyotrophic lateral sclerosis (ALS), including never in mitosis A (NIMA)-related kinase 1 (NEK1), a serine/threonine kinase that plays a key role in several cellular functions, such as DNA damage response and cell cycle regulation. Whole-exome sequencing studies have shown that NEK1 mutations are associated with an increased risk for ALS, where a significant enrichment of NEK1 loss-of-function (LOF) variants were found in individuals with ALS compared to controls. In particular, the p.Arg261His missense variant was associated with significantly increased disease susceptibility. This case series aims to understand the neuropathological phenotypes resulting from NEK1 mutations in ALS. We examined a cohort of three Scottish patients with a mutation in the NEK1 gene and evaluated the distribution and cellular expression of NEK1, as well as the abundance of phosphorylated TDP-43 (pTDP-43) aggregates, in the motor cortex compared to age- and sex-matched control tissue. We show pathological, cytoplasmic TDP-43 aggregates in all three NEK1-ALS cases. NEK1 protein staining revealed no immunoreactivity in two of the NEK1-ALS cases, indicating a LOF and corresponding to a reduction in NEK1 mRNA as detected by in situ hybridisation. However, the p.Arg261His missense mutation resulted in an increase in NEK1 mRNA molecules and abundant NEK1-positive cytoplasmic aggregates, with the same morphologic appearance, and within the same cells as co-occurring TDP-43 aggregates. Here we show the first neuropathological assessment of a series of ALS cases carrying mutations in the NEK1 gene. Specifically, we show that TDP-43 pathology is present in these cases and that potential NEK1 LOF can either be mediated through loss of NEK1 translation or through aggregation of NEK1 protein as in the case with p.Arg261His mutation, a potential novel pathological feature of NEK1-ALS.}, } @article {pmid38984697, year = {2024}, author = {Hasan, M and Alam, SM and Rahman, HZ and Khan, MAS and Huq, MR}, title = {Autonomic Dysfunction in Amyotrophic Lateral Sclerosis - A Case-Control Study.}, journal = {Acta medica academica}, volume = {53}, number = {1}, pages = {24-34}, pmid = {38984697}, issn = {1840-2879}, mesh = {Case-Control Studies ; *Amyotrophic Lateral Sclerosis/epidemiology ; *Autonomic Nervous System Diseases/epidemiology ; Bangladesh/epidemiology ; Tertiary Care Centers ; Humans ; Male ; Female ; Adolescent ; Young Adult ; Adult ; Middle Aged ; Upper Extremity/physiopathology ; Lower Extremity/physiopathology ; Sympathetic Nervous System ; }, abstract = {INTRODUCTION: This study aimed to explore autonomic nervous system involvement in amyotrophic lateral sclerosis (ALS) patients by evaluating sympathetic skin response (SSR).

MATERIALS AND METHODS: The study included 35 sporadic (ALS) patients (cases), and 35 healthy age and sex-matched participants (controls) aged <60 years. SSR was recorded in the electrophysiology lab of the Neurology Department of Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh. Patients with diseases associated with peripheral or autonomic neuropathy were excluded. Prolonged latency (delayed SSR) or an absent response was considered abnormal SSR.

RESULTS: SSR was found to be abnormal in 17 (48.6 %) ALS cases, with an absent response in the upper limbs of six cases (17.1%). Abnormal SSR was more prevalent in the lower limbs, with 33 (94.3%) and 20 (57.1%) cases having a delayed or absent response, respectively. In comparison, SSR was normal in all control participants (P-value <0.05). Abnormal SSR was significantly more common in the lower limbs of ALS cases with bulbar palsy than those without bulbar palsy (P-value=0.04). There was no association of SSR with disease severity and duration.

CONCLUSION: ALS is significantly associated with abnormal SSR, indicating autonomic nervous system involvement. There could also be an association between bulbar palsy and abnormal SSR among ALS patients. Further studies should be carried out to determine the association of abnormal SSR with disease severity, duration, and type.}, } @article {pmid38984619, year = {2024}, author = {Olney, N and Weiss, MD}, title = {Real world experience with sodium phenylbutyrate-taurursodiol for ALS: Lessons learned from a failed drug.}, journal = {Muscle & nerve}, volume = {70}, number = {3}, pages = {299-301}, doi = {10.1002/mus.28203}, pmid = {38984619}, issn = {1097-4598}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy ; *Phenylbutyrates/therapeutic use ; Male ; Female ; Middle Aged ; Treatment Failure ; Aged ; }, } @article {pmid38984582, year = {2025}, author = {Jiang, SS and Nie, HB and Hua, S and Xie, M and Xu, RS}, title = {Preliminary Analysis of Potentially Overlapping Differentially Expressed Proteins in Both the Spinal Cord and Brain of SOD1 G93A Mice.}, journal = {Current protein & peptide science}, volume = {26}, number = {1}, pages = {57-75}, pmid = {38984582}, issn = {1875-5550}, support = {30560042, 81160161, 81360198, 82160255//National Natural Science Foundation of China/ ; GJJ13198, GJJ170021//Education Department of Jiangxi Province/ ; [2014]-47, 20142BBG70062, 20171BAB- 215022, 20192BAB205043//Jiangxi provincial department of science and technology/ ; 20181019, 202210002, 202310119//Health and Family Planning Commission of Jiangxi province/ ; [2015] 108//Jiangxi Provincial Department of Science and Technology Gan Po Elite 555 (Jiangxi Finance Elite Education)/ ; }, mesh = {Animals ; *Spinal Cord/metabolism/pathology ; Mice ; *Brain/metabolism/pathology ; *Amyotrophic Lateral Sclerosis/metabolism/genetics/pathology ; Proteomics/methods ; Mice, Transgenic ; Superoxide Dismutase-1/genetics ; *Proteome/metabolism/genetics ; Disease Models, Animal ; Humans ; Gene Ontology ; Computational Biology ; Superoxide Dismutase ; }, abstract = {OBJECTIVE: Proteomic elucidation is an essential step in improving our understanding of the biological properties of proteins in amyotrophic lateral sclerosis (ALS).

METHODS: Preliminary proteomic analysis was performed on the spinal cord and brain of SOD1 G93A (TG) and wild-type (WT) mice using isobaric tags for relative and absolute quantitation.

RESULTS: Partial up- and downregulated proteins showing significant differences between TG and WT mice were identified, of which 105 proteins overlapped with differentially expressed proteins in both the spinal cord and brain of progression mice. Bioinformatic analyses using Gene Ontology, a cluster of orthologous groups, and Kyoto Encyclopedia of Genes and Genomes pathway revealed that the significantly up- and downregulated proteins represented multiple biological functions closely related to ALS, with 105 overlapping differentially expressed proteins in the spinal cord and brain at the progression stage of TG mice closely related to 122 pathways. Differentially expressed proteins involved in a set of molecular functions play essential roles in maintaining neural cell survival.

CONCLUSION: This study provides additional proteomic profiles of TG mice, including potential overlapping proteins in both the spinal cord and brain that participate in pathogenesis, as well as novel insights into the up- and downregulation of proteins involved in the pathogenesis of ALS.}, } @article {pmid38982381, year = {2024}, author = {Mioshi, E and Heal, S and Katangwe-Chigamba, T}, title = {'A lightbulb moment': carers' experiences of behavioural symptoms in motor neurone disease before and after MiNDToolkit.}, journal = {BMC neurology}, volume = {24}, number = {1}, pages = {238}, pmid = {38982381}, issn = {1471-2377}, support = {934-794/MNDA_/Motor Neurone Disease Association/United Kingdom ; 934-794/MNDA_/Motor Neurone Disease Association/United Kingdom ; }, mesh = {Humans ; *Caregivers/psychology ; Male ; *Motor Neuron Disease/psychology/therapy ; Female ; Middle Aged ; *Behavioral Symptoms/therapy/etiology ; Aged ; Adult ; Qualitative Research ; }, abstract = {BACKGROUND: To explore carers' experiences of behavioural symptoms in Motor Neurone Disease (MND), before and after using the MiNDToolkit, a novel internet-based psychoeducational intervention to support management of behavioural symptoms (BehSymp) in MND. The study also investigated carers' views and acceptability of MiNDToolkit.

METHODS: A qualitative process evaluation of carers engagement with, and acceptability of, the MiNDToolkit conducted using semi-structured interviews with carers (n = 11). All interviews were audio-recorded, professionally transcribed verbatim and analysed thematically.

RESULTS: Five themes were identified: (1) In the dark: carers' experiences and reactions to BehSymp; (2) Others can see: the role of HCPs in identifying symptoms - and perceived opportunities for carers to receive support; (3) Shedding light: carers implementation and perceived impact of the MiNDToolkit content; (4) Acceptability and carers' engagement with MiNDToolkit; (5) Future implementation. Carers' experience of BehSymp was particularly distressing when symptoms were apparently out of context. MiNDToolkit appeared to support learning that BehSymp were part of MND. Content resonated with carers, who reported learning about the full picture of MND, which led to acceptance and use of newly learned strategies. Engagement with the platform was good, with varied input from HCPs. Greater and nuanced involvement from HCPs seem important to support management of BehSymp. Recommendations for a full-scale trial emerged, including adding a paper booklet to accompany the intervention and creation of new modules on emotional lability, changes in relationships, and transitioning to a care home.

CONCLUSIONS: MiNDToolkit was acceptable to carers overall. Recommended improvements should be actioned in a full-scale trial.}, } @article {pmid38981325, year = {2024}, author = {Asghar, H and Tariq, A and Rasool, G and Hayat, A}, title = {Fabrication of a salivary amylase electrochemical sensor based on surface confined MWCNTs/β-cyclodextrin/starch architect for dental caries in clinical samples.}, journal = {Bioelectrochemistry (Amsterdam, Netherlands)}, volume = {160}, number = {}, pages = {108774}, doi = {10.1016/j.bioelechem.2024.108774}, pmid = {38981325}, issn = {1878-562X}, mesh = {*beta-Cyclodextrins/chemistry ; Humans ; *Nanotubes, Carbon/chemistry ; *Biosensing Techniques/methods ; *Starch/chemistry ; *Electrochemical Techniques/methods ; *Dental Caries/diagnosis ; Saliva/chemistry ; Limit of Detection ; Salivary alpha-Amylases/analysis/metabolism ; Electrodes ; }, abstract = {Salivary α-amylase (α-ALS) has drawn attention as a possible bioindicator for dental caries. Herein, combining the synergistic properties of multi-walled carbon nanotubes (MWCNTs), β-cyclodextrin (β-CD) and starch, an electrochemical sensor is constructed employing ferrocene (FCN) as an electrochemical indicator to oversee the progression of the enzymatic catalysis of α-ALS. The method involves a two-step chemical reaction sequence on a screen-printed carbon electrode (SPCE). X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy, Field emission scanning electron microscope (FE-SEM), and Dynamic light scattering (DLS) were used to characterize the synthesized material, while Static water Contact angle measurements, cyclic voltammetry (CV), and electrochemical impedance spectroscopy (EIS) were performed to monitor each step of sensor fabrication. The electrochemical sensor permitted to detect α-ALS within the linear range of 0.5-280 U mL[-1], revealing detection (LOD), and quantification (LOQ) values of 0.041 U mL[-1], and 0.159 U mL[-1], respectively. Remarkably, the sensor demonstrated exceptional specificity and selectivity, effectively discriminating against other interfering substances in saliva. Validation of the method involved analyzing α-ALS levels in artificial saliva with an accuracy range of 97 % to 103 %, as well as in real clinical saliva samples across various age groups.}, } @article {pmid38979791, year = {2024}, author = {Stabellini, N and Cullen, J and Bittencourt, MS and Moore, JX and Sutton, A and Nain, P and Hamerschlak, N and Weintraub, NL and Dent, S and Tsai, MH and Banerjee, A and Ghosh, AK and Sadler, D and Coughlin, SS and Barac, A and Shanahan, J and Montero, AJ and Guha, A}, title = {Allostatic Load/Chronic Stress and Cardiovascular Outcomes in Patients Diagnosed With Breast, Lung, or Colorectal Cancer.}, journal = {Journal of the American Heart Association}, volume = {13}, number = {14}, pages = {e033295}, pmid = {38979791}, issn = {2047-9980}, mesh = {Humans ; Female ; *Colorectal Neoplasms/epidemiology ; *Breast Neoplasms/epidemiology ; *Lung Neoplasms/epidemiology/diagnosis ; Middle Aged ; Male ; Retrospective Studies ; Aged ; *Cardiovascular Diseases/epidemiology ; *Allostasis/physiology ; Risk Assessment ; Risk Factors ; Stress, Psychological/complications ; }, abstract = {BACKGROUND: Cardiovascular disease and cancer share a common risk factor: chronic stress/allostatic load (AL). A 1-point increase in AL is linked to up to a 30% higher risk of major cardiac events (MACE) in patients with prostate cancer. However, AL's role in MACE in breast cancer, lung cancer, or colorectal cancer remains unknown.

METHODS AND RESULTS: Patients ≥18 years of age diagnosed with the mentioned 3 cancers of interest (2010-2019) and followed up at a large, hybrid academic-community practice were included in this retrospective cohort study. AL was modeled as an ordinal measure (0-11). Adjusted Fine-Gray competing risks regressions estimated the impact of AL precancer diagnosis on 2-year MACE (a composite of heart failure, ischemic stroke, acute coronary syndrome, and atrial fibrillation). The effect of AL changes over time on MACE was calculated via piecewise Cox regression (before, and 2 months, 6 months, and 1 year after cancer diagnosis). Among 16 467 patients, 50.5% had breast cancer, 27.9% had lung cancer, and 21.4% had colorectal cancer. A 1-point elevation in AL before breast cancer diagnosis corresponded to a 10% heightened associated risk of MACE (adjusted hazard ratio, 1.10 [95% CI, 1.06-1.13]). Similar findings were noted in lung cancer (adjusted hazard ratio, 1.16 [95% CI, 1.12-1.20]) and colorectal cancer (adjusted hazard ratio, 1.13 [95% CI, 1.08-1.19]). When considering AL as a time-varying exposure, the peak associated MACE risk occurred with a 1-point AL rise between 6 and 12 months post- breast cancer, lung cancer, and colorectal cancer diagnosis.

CONCLUSIONS: AL warrants investigation as a potential marker in these patients to identify those at elevated cardiovascular risk and intervene accordingly.}, } @article {pmid38979291, year = {2024}, author = {Weiss, A and Gilbert, JW and Flores, IVR and Belgrad, J and Ferguson, C and Dogan, EO and Wightman, N and Mocarski, K and Echeverria, D and Summers, A and Bramato, B and McHugh, N and Furgal, R and Yamada, N and Cooper, D and Monopoli, K and Godinho, BMDC and Hassler, MR and Yamada, K and Greer, P and Henninger, N and Brown, RH and Khvorova, A}, title = {RNAi-mediated silencing of SOD1 profoundly extends survival and functional outcomes in ALS mice.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {38979291}, issn = {2692-8205}, support = {T32 AI095213/AI/NIAID NIH HHS/United States ; R01 NS111990/NS/NINDS NIH HHS/United States ; S10 OD020012/OD/NIH HHS/United States ; R21 NR020231/NR/NINR NIH HHS/United States ; R21 NS131756/NS/NINDS NIH HHS/United States ; R01 NS104022/NS/NINDS NIH HHS/United States ; R35 GM131839/GM/NIGMS NIH HHS/United States ; U24 NS113844/NS/NINDS NIH HHS/United States ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative condition, with 20% of familial and 2-3% of sporadic cases linked to mutations in the cytosolic superoxide dismutase (SOD1) gene. Mutant SOD1 protein is toxic to motor neurons, making SOD1 gene lowering a promising approach, supported by preclinical data and the 2023 FDA approval of the GapmeR ASO targeting SOD1, tofersen. Despite the approval of an ASO and the optimism it brings to the field, the pharmacodynamics and pharmacokinetics of therapeutic SOD1 modulation can be improved. Here, we developed a chemically stabilized divalent siRNA scaffold (di-siRNA) that effectively suppresses SOD1 expression in vitro and in vivo. With optimized chemical modification, it achieves remarkable CNS tissue permeation and SOD1 silencing in vivo. Administered intraventricularly, di-siRNA[SOD1] extended survival in SOD1-G93A ALS mice, surpassing survival previously seen in these mice by ASO modalities, slowed disease progression, and prevented ALS neuropathology. These properties offer an improved therapeutic strategy for SOD1-mediated ALS and may extend to other dominantly inherited neurological disorders.}, } @article {pmid38979278, year = {2024}, author = {Arseni, D and Nonaka, T and Jacobsen, MH and Murzin, AG and Cracco, L and Peak-Chew, SY and Garringer, HJ and Kawakami, I and Suzuki, H and Onaya, M and Saito, Y and Murayama, S and Geula, C and Vidal, R and Newell, KL and Mesulam, M and Ghetti, B and Hasegawa, M and Ryskeldi-Falcon, B}, title = {Heteromeric amyloid filaments of ANXA11 and TDP-43 in FTLD-TDP Type C.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2024.06.25.600403}, pmid = {38979278}, issn = {2692-8205}, support = {P30 AG013854/AG/NIA NIH HHS/United States ; P30 AG072977/AG/NIA NIH HHS/United States ; }, abstract = {Neurodegenerative diseases are characterised by the abnormal filamentous assembly of specific proteins in the central nervous system [1] . Human genetic studies established a causal role for protein assembly in neurodegeneration [2] . However, the underlying molecular mechanisms remain largely unknown, which is limiting progress in developing clinical tools for these diseases. Recent advances in electron cryo-microscopy (cryo-EM) have enabled the structures of the protein filaments to be determined from patient brains [1] . All diseases studied to date have been characterised by the self-assembly of a single intracellular protein in homomeric amyloid filaments, including that of TAR DNA-binding protein 43 (TDP-43) in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-TDP) Types A and B [3,4] . Here, we used cryo-EM to determine filament structures from the brains of individuals with FTLD-TDP Type C, one of the most common forms of sporadic FTLD-TDP. Unexpectedly, the structures revealed that a second protein, annexin A11 (ANXA11), co-assembles with TDP-43 in heteromeric amyloid filaments. The ordered filament fold is formed by TDP-43 residues G282/284-N345 and ANXA11 residues L39-L74 from their respective low-complexity domains (LCDs). Regions of TDP-43 and ANXA11 previously implicated in protein-protein interactions form an extensive hydrophobic interface at the centre of the filament fold. Immunoblots of the filaments revealed that the majority of ANXA11 exists as a ∼22 kDa N-terminal fragment (NTF) lacking the annexin core domain. Immunohistochemistry of brain sections confirmed the co-localisation of ANXA11 and TDP-43 in inclusions, redefining the histopathology of FTLD-TDP Type C. This work establishes a central role for ANXA11 in FTLD-TDP Type C. The unprecedented formation of heteromeric amyloid filaments in human brain revises our understanding of amyloid assembly and may be of significance for the pathogenesis of neurodegenerative diseases.}, } @article {pmid38979270, year = {2024}, author = {Baghel, MS and Burns, GD and Tsapatsis, M and Mallika, AP and Cruz, ALF and Cao, T and Chen, XK and Rosa, I and Marx, SR and Ye, Y and Sun, S and Li, T and Wong, PC}, title = {Depletion of TDP-43 exacerbates tauopathy-dependent brain atrophy by sensitizing vulnerable neurons to caspase 3-mediated endoproteolysis of tau in a mouse model of Multiple Etiology Dementia.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {38979270}, issn = {2692-8205}, support = {R01 NS095969/NS/NINDS NIH HHS/United States ; R61 NS115161/NS/NINDS NIH HHS/United States ; F31 NS135935/NS/NINDS NIH HHS/United States ; R33 NS115161/NS/NINDS NIH HHS/United States ; RF1 NS127925/NS/NINDS NIH HHS/United States ; R01 AG078948/AG/NIA NIH HHS/United States ; }, abstract = {TDP-43 proteinopathy, initially disclosed in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), coexists with tauopathy in a variety of neurodegenerative disorders, termed multiple etiology dementias (MEDs), including Alzheimer's Disease (AD). While such co-pathology of TDP-43 is strongly associated with worsened neurodegeneration and steeper cognitive decline, the pathogenic mechanism underlying the exacerbated neuron loss remains elusive. The loss of TDP-43 splicing repression that occurs in presymptomatic ALS-FTD individuals suggests that such early loss could facilitate the pathological conversion of tau to accelerate neuron loss. Here, we report that the loss of TDP-43 repression of cryptic exons in forebrain neurons (CaMKII-CreER;Tardbp [f/f] mice) is necessary to exacerbate tauopathy-dependent brain atrophy by sensitizing vulnerable neurons to caspase 3-dependent cleavage of endogenous tau to promote tauopathy. Corroborating this finding within the human context, we demonstrate that loss of TDP-43 function in iPSC-derived cortical neurons promotes early cryptic exon inclusion and subsequent caspase 3-mediated endoproteolysis of tau. Using a genetic approach to seed tauopathy in CaMKII-CreER;Tardbp [f/f] mice by expressing a four-repeat microtubule binding domain of human tau, we show that the amount of tau seed positively correlates with levels of caspase 3-cleaved tau. Importantly, we found that the vulnerability of hippocampal neurons to TDP-43 depletion is dependent on the amount of caspase 3-cleaved tau: from most vulnerable neurons in the CA2/3, followed by those in the dentate gyrus, to the least in CA1. Taken together, our findings strongly support the view that TDP-43 loss-of-function exacerbates tauopathy-dependent brain atrophy by increasing the sensitivity of vulnerable neurons to caspase 3-mediated endoproteolysis of tau, resulting in a greater degree of neurodegeneration in human disorders with co-pathologies of tau and TDP-43. Our work thus discloses novel mechanistic insights and therapeutic targets for human tauopathies harboring co-pathology of TDP-43 and provides a new MED model for testing therapeutic strategies.}, } @article {pmid38979232, year = {2024}, author = {Keuss, MJ and Harley, P and Ryadnov, E and Jackson, RE and Zanovello, M and Wilkins, OG and Barattucci, S and Mehta, PR and Oliveira, MG and Parkes, JE and Sinha, A and Correa-Sánchez, AF and Oliver, PL and Fisher, EMC and Schiavo, G and Shah, M and Burrone, J and Fratta, P}, title = {Loss of TDP-43 induces synaptic dysfunction that is rescued by UNC13A splice-switching ASOs.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {38979232}, issn = {2692-8205}, support = {/WT_/Wellcome Trust/United Kingdom ; U54 NS123743/NS/NINDS NIH HHS/United States ; }, abstract = {TDP-43 loss of function induces multiple splicing changes, including a cryptic exon in the amyotrophic lateral sclerosis and fronto-temporal lobar degeneration risk gene UNC13A, leading to nonsense-mediated decay of UNC13A transcripts and loss of protein. UNC13A is an active zone protein with an integral role in coordinating pre-synaptic function. Here, we show TDP-43 depletion induces a severe reduction in synaptic transmission, leading to an asynchronous pattern of network activity. We demonstrate that these deficits are largely driven by a single cryptic exon in UNC13A. Antisense oligonucleotides targeting the UNC13A cryptic exon robustly rescue UNC13A protein levels and restore normal synaptic function, providing a potential new therapeutic approach for ALS and other TDP-43-related disorders.}, } @article {pmid38979013, year = {2024}, author = {Shi, W and Ding, R and Chen, Y and Ji, F and Ji, J and Ma, W and Jin, J}, title = {The HRD1-SEL1L ubiquitin ligase regulates stress granule homeostasis in couple with distinctive signaling branches of ER stress.}, journal = {iScience}, volume = {27}, number = {7}, pages = {110196}, pmid = {38979013}, issn = {2589-0042}, abstract = {Stress granules (SGs) are membrane-less cellular compartments which are dynamically assembled via biomolecular condensation mechanism when eukaryotic cells encounter environmental stresses. SGs are important for gene expression and cell fate regulation. Dysregulation of SG homeostasis has been linked to human neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Here we report that the HRD1-SEL1L ubiquitin ligase complex specifically regulates the homeostasis of heat shock-induced SGs through the ubiquitin-proteasome system (UPS) and the UPS-associated ATPase p97. Mechanistically, the HRD1-SEL1L complex mediates SG homeostasis through the BiP-coupled PERK-eIF2α signaling axis of endoplasmic reticulum (ER) stress, thereby coordinating the unfolded protein response (UPR) with SG dynamics. Furthermore, we show that the distinctive branches of ER stress play differential roles in SG homeostasis. Our study indicates that the UPS and the UPR together via the HRD1-SEL1L ubiquitin ligase to maintain SG homeostasis in a stressor-dependent manner.}, } @article {pmid38978682, year = {2024}, author = {Neumann, M and Kothare, H and Ramanarayanan, V}, title = {Multimodal Speech Biomarkers for Remote Monitoring of ALS Disease Progression.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, pmid = {38978682}, support = {R42 DC019877/DC/NIDCD NIH HHS/United States ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that severely impacts affected persons' speech and motor functions, yet early detection and tracking of disease progression remain challenging. The current gold standard for monitoring ALS progression, the ALS functional rating scale - revised (ALSFRS-R), is based on subjective ratings of symptom severity, and may not capture subtle but clinically meaningful changes due to a lack of granularity. Multimodal speech measures which can be automatically collected from patients in a remote fashion allow us to bridge this gap because they are continuous-valued and therefore, potentially more granular at capturing disease progression. Here we investigate the responsiveness and sensitivity of multimodal speech measures in persons with ALS (pALS) collected via a remote patient monitoring platform in an effort to quantify how long it takes to detect a clinically-meaningful change associated with disease progression. We recorded audio and video from 278 participants and automatically extracted multimodal speech biomarkers (acoustic, orofacial, linguistic) from the data. We find that the timing alignment of pALS speech relative to a canonical elicitation of the same prompt and the number of words used to describe a picture are the most responsive measures at detecting such change in both pALS with bulbar (n = 36) and non-bulbar onset (n = 107). Interestingly, the responsiveness of these measures is stable even at small sample sizes. We further found that certain speech measures are sensitive enough to track bulbar decline even when there is no patient-reported clinical change, i.e. the ALSFRS-R speech score remains unchanged at 3 out of a total possible score of 4. The findings of this study have the potential to facilitate improved, accelerated and cost-effective clinical trials and care.}, } @article {pmid38978196, year = {2024}, author = {Huang, X and Wu, J and Zhang, N and Teng, J and Yang, Q and Zhang, Y and Yin, T and Zhou, W and Fan, D and Ye, S}, title = {Smell loss is associated with cognitive impairment in amyotrophic lateral sclerosis patients.}, journal = {CNS neuroscience & therapeutics}, volume = {30}, number = {7}, pages = {e14851}, pmid = {38978196}, issn = {1755-5949}, support = {82001350//National Natural Science Foundation of China/ ; 2021ZD0204200//STI2030-Major Projects/ ; JCTD-2021-06//The Chinese Academy of Sciences Grants/ ; YCXJ-JZ-2022-007//Beijing E-Town Cooperation & Development Foundation/ ; YJXJ-JZ-2021-0014//Beijing E-Town Cooperation & Development Foundation/ ; DL2019002//PUTH Cohort Construction Project/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/complications/psychology/epidemiology ; Male ; Female ; Middle Aged ; *Cognitive Dysfunction/epidemiology/etiology ; Aged ; *Olfaction Disorders/etiology/epidemiology ; Adult ; }, abstract = {BACKGROUND: Smell loss significantly impacts the quality of life in patients. However, there is limited research on smell loss in individuals with amyotrophic lateral sclerosis (ALS), and the correlation between smell loss and cognitive impairment is unclear. This study aimed to investigate the correlation between smell loss and cognition impairment in ALS patients.

METHODS: The study included 216 ALS patients. The Edinburgh Cognitive and Behavioural ALS Screen (ECAS) and smell identification test specifically for the Chinese population (CSIT) were administered to evaluate participants' cognitive and olfactory function, respectively.

RESULTS: After covarying for age, sex, BMI, education level, degree of hunger, dietary bias, eagerness for food, stress, smoking status, alcohol consumption, and upper respiratory tract infection (URTI) or rhinitis, CSIT scores were significantly correlated with ECAS scores (r = 0.162, p = 0.028), especially the ALS-specific scores (r = 0.158, p = 0.031). Even after excluding patients with URTI or rhinitis, the results were similar. CSIT scores were significantly correlated with ECAS scores (r = 0.224, p = 0.011), especially the ALS-specific scores (r = 0.205, p = 0.019).

CONCLUSION: In patients with ALS, smell loss is significantly correlated with cognitive impairment, particularly frontotemporal dysfunction. Cognitive dysfunction may lead to worse olfactory performance in ALS patients.}, } @article {pmid38978024, year = {2024}, author = {Endalamaw, A and Gilks, CF and Ambaw, F and Shiferaw, WS and Assefa, Y}, title = {Explaining inequity in knowledge, attitude, and services related to HIV/AIDS: a systematic review.}, journal = {BMC public health}, volume = {24}, number = {1}, pages = {1815}, pmid = {38978024}, issn = {1471-2458}, mesh = {Humans ; *HIV Infections/psychology ; *Health Knowledge, Attitudes, Practice ; Healthcare Disparities ; }, abstract = {BACKGROUND: Equitable service provision and coverage are important responses to end the threat of the HIV/AIDS pandemic. Understanding inequity supports policies and programmes to deliver tailored interventions. There is continuous evidence generation on inequity in HIV/AIDS services. However, there was a lack of evidence on the global picture of inequity in behavioural and biomedical services related to HIV/AIDS. This systematic review assessed inequities in knowledge, attitude, HIV testing, and ART coverage across individual-level social groups and multiple (dis)advantage categories.

METHODS: This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline, with a PROSPERO registration number CRD42024521247. The risk of bias was assessed by using Hoy et al's and Joanna Brigg's quality appraisal checklists for cross-sectional quantitative and qualitative studies, respectively. The search date was from inception to the final database search date (May 29, 2023). The included articles were either quantitative or qualitative studies. We used mixed-methods approach to analyse the data from the review articles. Quantitative descriptive analysis was conducted to estimate frequency of articles published from different countries around the world. Qualitative content analysis of the findings from the original studies was conducted using the PROGRESS plus framework which stands for: place of residence, occupation or employment status, gender, religion, education status, socioeconomic status, and social capital.

RESULTS: Out of 6,029 articles that were accessed and screened, only 72 articles met the inclusion criteria. More articles on HIV-related equity in knowledge, attitude, testing, and ART were published in developed countries than in developing countries. Individuals from higher-income households had better knowledge about HIV/AIDS. Unfavourable attitudes towards people living with HIV and HIV/AIDS-associated stigma were common among women. HIV/AIDS service coverage (HIV testing or ART coverage) was higher among richer and urban residents. HIV/AIDS-associated stigma and lower levels of knowledge about HIV/AIDS were observed among multiple disadvantageous groups due to the intersection of two or more identities.

CONCLUSIONS: The current review revealed that there have been disparities in HIV/AIDS services between social classes. Ending service disparity towards the global threat of HIV/AIDS demands tailored interventions based on socially disadvantaged groups (e.g., poor, rural dwellers, and women) and intersectional determinants. There is a need to understand the deep-rooted causes of inequity and the challenges that an equity-oriented system faces over time. More studies on inequity are needed, including intersectional inequity, which has been rarely studied in developing countries.}, } @article {pmid38977678, year = {2024}, author = {M Amaral, D and Soares, DF and Gromicho, M and de Carvalho, M and Madeira, SC and Tomás, P and Aidos, H}, title = {Temporal stratification of amyotrophic lateral sclerosis patients using disease progression patterns.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {5717}, pmid = {38977678}, issn = {2041-1723}, support = {101017598//EC | EU Framework Programme for Research and Innovation H2020 | H2020 European Institute of Innovation and Technology (H2020 The European Institute of Innovation and Technology)/ ; 101017598//EC | EU Framework Programme for Research and Innovation H2020 | H2020 European Institute of Innovation and Technology (H2020 The European Institute of Innovation and Technology)/ ; 101017598//EC | EU Framework Programme for Research and Innovation H2020 | H2020 European Institute of Innovation and Technology (H2020 The European Institute of Innovation and Technology)/ ; 101017598//EC | EU Framework Programme for Research and Innovation H2020 | H2020 European Institute of Innovation and Technology (H2020 The European Institute of Innovation and Technology)/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/pathology/physiopathology ; Humans ; *Disease Progression ; Male ; Cluster Analysis ; Female ; Middle Aged ; Aged ; }, abstract = {Identifying groups of patients with similar disease progression patterns is key to understand disease heterogeneity, guide clinical decisions and improve patient care. In this paper, we propose a data-driven temporal stratification approach, ClusTric, combining triclustering and hierarchical clustering. The proposed approach enables the discovery of complex disease progression patterns not found by univariate temporal analyses. As a case study, we use Amyotrophic Lateral Sclerosis (ALS), a neurodegenerative disease with a non-linear and heterogeneous disease progression. In this context, we applied ClusTric to stratify a hospital-based population (Lisbon ALS Clinic dataset) and validate it in a clinical trial population. The results unravelled four clinically relevant disease progression groups: slow progressors, moderate bulbar and spinal progressors, and fast progressors. We compared ClusTric with a state-of-the-art method, showing its effectiveness in capturing the heterogeneity of ALS disease progression in a lower number of clinically relevant progression groups.}, } @article {pmid38977656, year = {2025}, author = {Han, M and Raymond, J and Larson, TC and Mehta, P and Horton, DK}, title = {Comparison of Demographics: National Amyotrophic Lateral Sclerosis Registry and Clinical Trials Data.}, journal = {Journal of racial and ethnic health disparities}, volume = {12}, number = {4}, pages = {2270-2278}, pmid = {38977656}, issn = {2196-8837}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/ethnology/epidemiology/therapy ; *Registries/statistics & numerical data ; Middle Aged ; Male ; Female ; Aged ; *Clinical Trials as Topic/statistics & numerical data ; Adult ; United States/epidemiology ; Databases, Factual ; Demography ; }, abstract = {OBJECTIVE: To characterize the participant demographics in the Pooled Resource Open-Access ALS Clinical Trials (PRO-ACT) database compared with the web-portal National Amyotrophic Lateral Sclerosis (ALS) Registry (the Registry).

METHODS: Demographics and ALS symptom information were compared between the self-reported registrant data in the Registry web portal (2010-2021) and the latest available PRO-ACT data (updated August 2022), which is a collection of clinical trials data.

RESULTS: Greater percentages of younger (≤ 59 years old) but smaller percentages of older (60 + years old) participants were represented in PRO-ACT compared to Registry. Enrollment for minority race groups was greater in the Registry portal data, but race information was largely missing/unknown in PRO-ACT database. Median age at the time of diagnosis and age at the time of symptom onset were significantly higher for Registry enrollees compared to the participants of PRO-ACT. Symptom onset sites were similarly reported, but duration between self-noted symptom onset and diagnosis was slight, but significantly longer for the Registry enrollees (11 vs. 9 months). Hispanic were as likely as non-Hispanic to participate in research studies, based on the Registry data.

CONCLUSION: There was a notable difference in the age distribution and minority representation of enrollees between the PRO-ACT and Registry study populations. Age distribution in the PRO-ACT database skewed to a younger and less diverse cohort. Despite the clinical heterogeneity and complex disease mechanism of ALS, identifying the underrepresented demographic niche in the PRO-ACT and Registry study populations can help improve patient participation and criteria for patient selection to enhance generalizability.}, } @article {pmid38976599, year = {2024}, author = {Xu, Z and Xu, R}, title = {Current potential diagnostic biomarkers of amyotrophic lateral sclerosis.}, journal = {Reviews in the neurosciences}, volume = {35}, number = {8}, pages = {917-931}, pmid = {38976599}, issn = {2191-0200}, mesh = {*Amyotrophic Lateral Sclerosis/diagnosis/metabolism ; Humans ; *Biomarkers/metabolism ; Oxidative Stress/physiology ; Proteomics/methods ; Animals ; }, abstract = {Amyotrophic lateral sclerosis (ALS) currently lacks the useful diagnostic biomarkers. The current diagnosis of ALS is mainly depended on the clinical manifestations, which contributes to the diagnostic delay and be difficult to make the accurate diagnosis at the early stage of ALS, and hinders the clinical early therapeutics. The more and more pathogenesis of ALS are found at the last 30 years, including excitotoxicity, the oxidative stress, the mitochondrial dysfunction, neuroinflammation, the altered energy metabolism, the RNA misprocessing and the most recent neuroimaging findings. The findings of these pathogenesis bring the new clues for searching the diagnostic biomarkers of ALS. At present, a large number of relevant studies about the diagnostic biomarkers are underway. The ALS pathogenesis related to the diagnostic biomarkers might lessen the diagnostic reliance on the clinical manifestations. Among them, the cortical altered signatures of ALS patients derived from both structural and functional magnetic resonance imaging and the emerging proteomic biomarkers of neuronal loss and glial activation in the cerebrospinal fluid as well as the potential biomarkers in blood, serum, urine, and saliva are leading a new phase of biomarkers. Here, we reviewed these current potential diagnostic biomarkers of ALS.}, } @article {pmid38975625, year = {2024}, author = {Berkman, O and Raveh, E and Harpaz, E and Kreitman, R and Ben-Ami, E and Nechushtan, E and Birman, N and Drory, VE}, title = {Changes in saccadic intrusions over time as an objective biomarker to follow ALS disease progression.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {25}, number = {7-8}, pages = {760-766}, doi = {10.1080/21678421.2024.2376732}, pmid = {38975625}, issn = {2167-9223}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology/diagnosis ; *Disease Progression ; Female ; Middle Aged ; Male ; Aged ; *Saccades/physiology ; Ocular Motility Disorders/etiology/diagnosis/physiopathology ; Biomarkers ; }, abstract = {Objective: Saccadic Intrusions (SIs) are abnormal eye movements during gaze fixation. Studies have indicated the clinical relevance of SIs, especially of square wave jerks (SWJ) in ALS. We used a software-based platform to extract SIs as a part of an interventional drug trial. The objective was to examine SIs' change over time as a potential biomarker of ALS disease progression. Methods: 28 ALS patients (61.95 ± 8.6 years) were assessed with the revised ALS Functional Rating Scale (ALSFRS-R) and with an oculometric test. Changes of SIs over time and correlations with ALSFRS-R and its bulbar subscale were calculated. A power calculation was conducted to understand the practical implications of results. Results: A significant increase of SWJ over trial duration was observed, with an increase in frequency (mean rise of 0.14 ± 0.28, p < 0.01), amplitude (0.001 ± 0.0016 degrees, p < 0.005), overall duration of SWJ (0.13 ± 0.25, in %, p < 0.01), and in their relative part out of all intrusions (0.18 ± 0.32, in %, p < 0.005). Negative correlations were found with the bulbar subscale (R=-0.43, -0.41, -0.39 and -0.47, respectively, p < 0.001). The required sample size for observing a 40% reduction in bulbar aspects when using the oculometric test (α = 0.05 and β = 0.8), was found to be 150 patients per arm, compared with 200 patients using the bulbar subscale. Conclusions: Evaluation of saccadic intrusions during fixation was able to detect disease progression over time, correlated with ALSFRS-R bulbar subscale. Eye movements can potentially serve as an objective biomarker in ALS clinical trials and reduce the required sample size to show clinical effect of therapies.}, } @article {pmid38975145, year = {2024}, author = {Zhang, J and Xie, D and Jiao, D and Zhou, S and Liu, S and Ju, Z and Hu, L and Qi, L and Yao, C and Zhao, C}, title = {From inflammatory signaling to neuronal damage: Exploring NLR inflammasomes in ageing neurological disorders.}, journal = {Heliyon}, volume = {10}, number = {12}, pages = {e32688}, pmid = {38975145}, issn = {2405-8440}, abstract = {The persistence of neuronal degeneration and damage is a major obstacle in ageing medicine. Nucleotide-binding oligomerization domain (NOD)-like receptors detect environmental stressors and trigger the maturation and secretion of pro-inflammatory cytokines that can cause neuronal damage and accelerate cell death. NLR (NOD-like receptors) inflammasomes are protein complexes that contain NOD-like receptors. Studying the role of NLR inflammasomes in ageing-related neurological disorders can provide valuable insights into the mechanisms of neurodegeneration. This includes investigating their activation of inflammasomes, transcription, and capacity to promote or inhibit inflammatory signaling, as well as exploring strategies to regulate NLR inflammasomes levels. This review summarizes the use of NLR inflammasomes in guiding neuronal degeneration and injury during the ageing process, covering several neurological disorders such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, stroke, and peripheral neuropathies. To improve the quality of life and slow the progression of neurological damage, NLR-based treatment strategies, including inhibitor-related therapies and physical therapy, are presented. Additionally, important connections between age-related neurological disorders and NLR inflammasomes are highlighted to guide future research and facilitate the development of new treatment options.}, } @article {pmid38974930, year = {2024}, author = {Aziz, S and Barratt, J and Wilson-Baig, N and Lachowycz, K and Major, R and Barnard, EBG and Rees, P}, title = {A protocol for the ERICA-ARREST feasibility study of Emergency Resuscitative Endovascular Balloon occlusion of the Aorta in Out-of-Hospital Cardiac Arrest.}, journal = {Resuscitation plus}, volume = {19}, number = {}, pages = {100688}, pmid = {38974930}, issn = {2666-5204}, abstract = {BACKGROUND: Fewer than one in ten out-of-hospital cardiac arrest (OHCA) patients survive to hospital discharge in the UK. For prehospital teams to improve outcomes in patients who remain in refractory OHCA despite advanced life support (ALS); novel strategies that increase the likelihood of return of spontaneous circulation, whilst preserving cerebral circulation, should be investigated. Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) has been shown to improve coronary and cerebral perfusion during cardiopulmonary resuscitation. Early, prehospital initiation of REBOA may improve outcomes in patients who do not respond to standard ALS. However, there are significant clinical, technical, and logistical challenges with rapidly delivering prehospital REBOA in OHCA; and the feasibility of delivering this intervention in the UK urban-rural setting has not been evaluated.

METHODS: The Emergency Resuscitative Endovascular Balloon Occlusion of the Aorta in Out-of-Hospital Cardiac Arrest (ERICA-ARREST) study is a prospective, single-arm, interventional feasibility study. The trial will enrol 20 adult patients with non-traumatic OHCA. The primary objective is to assess the feasibility of performing Zone I (supra-coeliac) aortic occlusion in patients who remain in OHCA despite standard ALS in the UK prehospital setting. The trial's secondary objectives are to describe the hemodynamic and physiological responses to aortic occlusion; to report key time intervals; and to document adverse events when performing REBOA in this context.

DISCUSSION: Using compressed geography, and targeted dispatch, alongside a well-established femoral arterial access programme, the ERICA-ARREST study will assess the feasibility of deploying REBOA in OHCA in a mixed UK urban and rural setting.Trial registration.ClinicalTrials.gov (NCT06071910), registration date October 10, 2023, https://classic.clinicaltrials.gov/ct2/show/NCT06071910.}, } @article {pmid38973130, year = {2025}, author = {Corcia, P and Guy, N and Pradat, PF and Soriani, MH and Verschueren, A and Couratier, P}, title = {Treatment continuity of amyotrophic lateral sclerosis with available riluzole formulations: state of the art and current challenges in a 'real-world' setting.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {26}, number = {1-2}, pages = {15-21}, doi = {10.1080/21678421.2024.2375330}, pmid = {38973130}, issn = {2167-9223}, mesh = {*Riluzole/therapeutic use/administration & dosage ; Humans ; *Amyotrophic Lateral Sclerosis/drug therapy/complications ; *Neuroprotective Agents/administration & dosage/therapeutic use ; Deglutition Disorders/drug therapy/etiology ; Treatment Outcome ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a rare multisystem neurodegenerative disease leading to death due to respiratory failure. Riluzole was the first disease modifying treatment approved in ALS. Randomized clinical trials showed a significant benefit of riluzole on survival in the months following randomization, with a good safety profile. 'Real-world' studies suggested that the survival benefit of riluzole is substantially greater, with an extended survival ranging between 6 and 19 months. The main limiting associated adverse effects of riluzole are non-severe gastrointestinal complications and an elevation of liver enzymes, observed in 10% of patients. While different classes of drugs have been approved in some countries, riluzole remains the gold standard of therapy. Dysphagia induced by ALS is a major challenge for food intake and riluzole administration. Tablet crushing is associated with a loss of drug intake and a risk of powder aspiration, which jeopardizes the benefits of riluzole. Riluzole oral suspension (ROS) and oral film (ROF) allow riluzole intake in patients with dysphagia. Both formulations are bioequivalent to riluzole tablets with a good safety profile albeit transient oral hypoaesthesia. In case of severe dysphagia, ROS can be used with percutaneous endoscopic gastrostomy. ROF, the last approved formulation, requires low swallowing capacities and may contribute to maintain the efficacy of riluzole when tablets are inadequate according to patient's status and/or preferences. To optimize treatment continuity in newly diagnosed patients, the expected psychological impact of formulation switching that may be perceived as the sign of disease progression should be anticipated.}, } @article {pmid38972779, year = {2024}, author = {Pelaez, MC and Fiore, F and Larochelle, N and Dabbaghizadeh, A and Comaduran, MF and Arbour, D and Minotti, S and Marcadet, L and Semaan, M and Robitaille, R and Nalbantoglu, JN and Sephton, CF and Durham, HD}, title = {Reversal of cognitive deficits in FUS[R521G] amyotrophic lateral sclerosis mice by arimoclomol and a class I histone deacetylase inhibitor independent of heat shock protein induction.}, journal = {Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics}, volume = {21}, number = {5}, pages = {e00388}, pmid = {38972779}, issn = {1878-7479}, mesh = {Animals ; *Amyotrophic Lateral Sclerosis/drug therapy/genetics/metabolism ; *Histone Deacetylase Inhibitors/pharmacology/therapeutic use ; Mice ; *Mice, Transgenic ; Heat-Shock Proteins/genetics/metabolism ; Hydroxylamines/pharmacology/therapeutic use ; Cognitive Dysfunction/drug therapy/metabolism ; Disease Models, Animal ; Spinal Cord/drug effects/metabolism ; Humans ; Mice, Inbred C57BL ; }, abstract = {Protein misfolding and mislocalization are common to both familial and sporadic forms of amyotrophic lateral sclerosis (ALS). Maintaining proteostasis through induction of heat shock proteins (HSP) to increase chaperoning capacity is a rational therapeutic strategy in the treatment of ALS. However, the threshold for upregulating stress-inducible HSPs remains high in neurons, presenting a therapeutic obstacle. This study used mouse models expressing the ALS variants FUS[R521G] or SOD1[G93A] to follow up on previous work in cultured motor neurons showing varied effects of the HSP co-inducer, arimoclomol, and class I histone deacetylase (HDAC) inhibitors on HSP expression depending on the ALS variant being expressed. As in cultured neurons, neither expression of the transgene nor drug treatments induced expression of HSPs in cortex, spinal cord or muscle of FUS[R521G] mice, indicating suppression of the heat shock response. Nonetheless, arimoclomol, and RGFP963, restored performance on cognitive tests and improved cortical dendritic spine densities. In SOD1[G93A] mice, multiple HSPs were upregulated in hindlimb skeletal muscle, but not in lumbar spinal cord with the exception of HSPB1 associated with astrocytosis. Drug treatments improved contractile force but reduced the increase in HSPs in muscle rather than facilitating their expression. The data point to mechanisms other than amplification of the heat shock response underlying recovery of cognitive function in ALS-FUS mice by arimoclomol and class I HDAC inhibition and suggest potential benefits in counteracting cognitive impairment in ALS, frontotemporal dementia and related disorders.}, } @article {pmid38972199, year = {2024}, author = {Rosén, C and Mitre, B and Nellgård, B and Axelsson, M and Constantinescu, R and Andersen, PM and Dalla, K and Blennow, K and Nilsson, G and Zetterberg, H and Rosén, H}, title = {High levels of neurofilament light and YKL-40 in cerebrospinal fluid are related to poor outcome in ALS.}, journal = {Journal of the neurological sciences}, volume = {463}, number = {}, pages = {123112}, doi = {10.1016/j.jns.2024.123112}, pmid = {38972199}, issn = {1878-5883}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/cerebrospinal fluid/diagnosis/blood ; *Chitinase-3-Like Protein 1/cerebrospinal fluid/blood ; Female ; Male ; *Neurofilament Proteins/cerebrospinal fluid ; Middle Aged ; Aged ; *Biomarkers/cerebrospinal fluid ; Glial Fibrillary Acidic Protein/cerebrospinal fluid ; Disease Progression ; Adult ; Membrane Glycoproteins ; Receptors, Immunologic ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurological disease without effective treatment. No pathognomonic test can diagnose ALS in sporadic cases. Routine investigation in suspected cases includes neurological examination, imaging of the brain and spine and electromyography supported by blood and cerebrospinal fluid (CSF) analyses. The ALS diagnosis is made by clinical judgement and results from examinations. We aimed to study if the CSF biomarkers neurofilament light protein (NFL), glial fibrillary acidic protein (GFAP), YKL-40, soluble amyloid precursor protein (sAPP) α and β, and soluble triggering receptor expressed on myeloid cells 2 (sTREM2) were associated with ALS diagnosis and could predict disease progression. Eighty-one patients with suspected ALS were included after referral to the neurological clinic at Sahlgrenska University Hospital. Fifty-nine patients were diagnosed having ALS, while 22 patients were given alternative diagnoses and labeled ALS mimics. Finally, 25 age-matched neurologically intact individuals were used as controls. ALS patients had significantly higher CSF levels of NFL than controls and mimics. Levels of YKL-40 and GFAP were significantly higher in ALS patients compared with controls. No difference was found between study groups when comparing levels of sAPPα, sAPPβ and sTREM2. Further, elevated levels of NFL and YKL-40 were associated with an increased hazard of death and the annual decline in ALSFRS-R. We also found that patients with elevated levels of both NFL and YKL-40 had a particularly poor prognosis. The results demonstrate the usefulness of CSF biomarkers in the diagnosis and prognostication of ALS.}, } @article {pmid38971939, year = {2024}, author = {Gomez, D and Selvaraj, MG and Casas, J and Mathiyazhagan, K and Rodriguez, M and Assefa, T and Mlaki, A and Nyakunga, G and Kato, F and Mukankusi, C and Girma, E and Mosquera, G and Arredondo, V and Espitia, E}, title = {Advancing common bean (Phaseolus vulgaris L.) disease detection with YOLO driven deep learning to enhance agricultural AI.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {15596}, pmid = {38971939}, issn = {2045-2322}, mesh = {*Phaseolus/virology/microbiology ; *Deep Learning ; *Plant Diseases/virology/microbiology ; Agriculture/methods ; Plant Leaves/virology/microbiology ; Africa ; Colombia ; }, abstract = {Common beans (CB), a vital source for high protein content, plays a crucial role in ensuring both nutrition and economic stability in diverse communities, particularly in Africa and Latin America. However, CB cultivation poses a significant threat to diseases that can drastically reduce yield and quality. Detecting these diseases solely based on visual symptoms is challenging, due to the variability across different pathogens and similar symptoms caused by distinct pathogens, further complicating the detection process. Traditional methods relying solely on farmers' ability to detect diseases is inadequate, and while engaging expert pathologists and advanced laboratories is necessary, it can also be resource intensive. To address this challenge, we present a AI-driven system for rapid and cost-effective CB disease detection, leveraging state-of-the-art deep learning and object detection technologies. We utilized an extensive image dataset collected from disease hotspots in Africa and Colombia, focusing on five major diseases: Angular Leaf Spot (ALS), Common Bacterial Blight (CBB), Common Bean Mosaic Virus (CBMV), Bean Rust, and Anthracnose, covering both leaf and pod samples in real-field settings. However, pod images are only available for Angular Leaf Spot disease. The study employed data augmentation techniques and annotation at both whole and micro levels for comprehensive analysis. To train the model, we utilized three advanced YOLO architectures: YOLOv7, YOLOv8, and YOLO-NAS. Particularly for whole leaf annotations, the YOLO-NAS model achieves the highest mAP value of up to 97.9% and a recall of 98.8%, indicating superior detection accuracy. In contrast, for whole pod disease detection, YOLOv7 and YOLOv8 outperformed YOLO-NAS, with mAP values exceeding 95% and 93% recall. However, micro annotation consistently yields lower performance than whole annotation across all disease classes and plant parts, as examined by all YOLO models, highlighting an unexpected discrepancy in detection accuracy. Furthermore, we successfully deployed YOLO-NAS annotation models into an Android app, validating their effectiveness on unseen data from disease hotspots with high classification accuracy (90%). This accomplishment showcases the integration of deep learning into our production pipeline, a process known as DLOps. This innovative approach significantly reduces diagnosis time, enabling farmers to take prompt management interventions. The potential benefits extend beyond rapid diagnosis serving as an early warning system to enhance common bean productivity and quality.}, } @article {pmid38971043, year = {2024}, author = {Malmström, N and Öhlén, J and Jakobsson Larsson, B and Nilsson, S and Nygren, I and M Andersen, P and Ozanne, A}, title = {Adolescents' challenging and grief-filled transitions when living with a parent with ALS: A qualitative interpretive study.}, journal = {Social science & medicine (1982)}, volume = {354}, number = {}, pages = {117063}, doi = {10.1016/j.socscimed.2024.117063}, pmid = {38971043}, issn = {1873-5347}, mesh = {Humans ; *Qualitative Research ; *Amyotrophic Lateral Sclerosis/psychology ; Sweden ; *Grief ; Female ; Male ; Adolescent ; Adult ; Adaptation, Psychological ; Child ; Young Adult ; Parents/psychology ; Parent-Child Relations ; }, abstract = {OBJECTIVE: The study aimed to explore the meaning for adolescents of living with a parent with amyotrophic lateral sclerosis (ALS).

METHODS: The design is qualitative. Interviews were conducted between December 2020 and April 2022 with 11 adolescents (8-25 y), living in households with a parent with ALS in Sweden. The analysis was phenomenologically hermeneutical.

RESULTS: The adolescents were in a difficult and exposed situation, especially if the parent had a severe disability and assistant care providers were in the home. Witnessing the gradual loss of the parent in an indefinite battle against time, while still needing them, elicited grief-filled and hard-to-manage emotions. Everyday life was turned upside down, resulting in greater responsibility for the adolescents, not only in helping with household chores and assisting the ill parent, but also in emotionally protecting both parents. It forced the adolescents to mature faster and put their own life on hold, triggering experiences of being limited. This, together with changing family roles yet being more attached to home, reinforced the imbalance in the adolescents' lives. The interpreted whole of the adolescents' narratives revealed that living with a parent with ALS meant a challenging and grieving transition during an already transition-filled adolescence, which left the adolescents struggling to keep a foothold on a life torn apart.

CONCLUSION: The unbalanced life situation may hinder the adolescents' identity formation and emancipation, which are developmentally important for managing a healthy and independent adulthood. The results emphasize the importance of early targeted support to reach this vulnerable group in order to secure their health.}, } @article {pmid38970668, year = {2024}, author = {Ludolph, AC and Dietrich, J and Dreyhaupt, J and Kassubek, J and Del Tredici, K and Rosenbohm, A}, title = {Clinical spreading of muscle weakness in amyotrophic lateral sclerosis (ALS): a study in 910 patients.}, journal = {Journal of neurology}, volume = {271}, number = {8}, pages = {5357-5367}, pmid = {38970668}, issn = {1432-1459}, support = {LU 336/15-1//Deutsche Forschungsgemeinschaft/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology/pathology/diagnosis ; Male ; Female ; Middle Aged ; Aged ; *Muscle Weakness/physiopathology/etiology/pathology ; Disease Progression ; Cohort Studies ; Adult ; Germany/epidemiology ; }, abstract = {BACKGROUND: Neuroanatomical staging of sporadic amyotrophic lateral sclerosis (ALS) indicates that neurodegeneration may spread corticofugally.

METHODS: We conducted an observational study to define the initial sites of disease onset and the clinical progression ('spreading patterns') of motor deficits in a cohort of 910 ALS patients in Germany.

RESULTS: Mean age of ALS onset was 59.0 ± 12.6 years for males and 61.2 ± 10.5 years for females, the mean ALSFRS-R was 35.1 ± 9.2, and 7.7% of the cohort reported a family history. Onset of motor symptoms was bulbar/upper limb in 26.8%/35.9%, the right arm initially being slightly more often affected than the left (18.5% vs.16.3%). Testing on concordance of handedness and onset in the dominant arm did not reach significance. Lower limb onset was observed in 37.3%. Unilateral limb onset patients reported horizontal spreading about three times more often than vertical spreading. 71/244 bulbar onset patients reported spreading pattern to the legs, and 17/339 lumbar onset patients reported spreading secondarily to the bulbar region.

DISCUSSION: Our results indicate that, although the phenotype of so-called 'spinal' or 'intraspinal' spreading predominated, we also observed an additional clinical spreading pattern: 29.1% of patients with bulbar onset experienced spreading clinically to the legs (vice versa in 5.0% of lumbar onset patients). For obvious neuroanatomical reasons, this pattern hardly can be explained solely by a 'spinal' or an 'intraspinal' pattern of spreading. Instead, these findings complement insights from previous clinical and clinicopathological studies supporting a cortical initiation of ALS.}, } @article {pmid38970158, year = {2024}, author = {Li, Z and Wen, J and Wu, W and Dai, Z and Liang, X and Zhang, N and Cheng, Q and Zhang, H}, title = {Causal relationship and shared genes between air pollutants and amyotrophic lateral sclerosis: A large-scale genetic analysis.}, journal = {CNS neuroscience & therapeutics}, volume = {30}, number = {7}, pages = {e14812}, pmid = {38970158}, issn = {1755-5949}, support = {2023CQBSHTB3095//Chongqing Postdoctoral Research Special Funding Project/ ; CSTB2023NSCQBHX0002//Chongqing Postdoctoral Science Foundation/ ; 2023MD734131//China Postdoctoral Science Foundation/ ; 2023RC3074//Hunan Youth Science and Technology Talent Project/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/genetics/epidemiology ; Humans ; *Polymorphism, Single Nucleotide/genetics ; *Genome-Wide Association Study ; *Air Pollutants/adverse effects/toxicity ; *Mendelian Randomization Analysis ; Genetic Predisposition to Disease/genetics ; Particulate Matter/adverse effects ; }, abstract = {OBJECTIVE: Air pollutants have been reported to have a potential relationship with amyotrophic lateral sclerosis (ALS). The causality and underlying mechanism remained unknown despite several existing observational studies. We aimed to investigate the potential causality between air pollutants (PM2.5, NOX, and NO2) and the risk of ALS and elucidate the underlying mechanisms associated with this relationship.

METHODS: The data utilized in our study were obtained from publicly available genome-wide association study data sets, in which single nucleotide polymorphisms (SNPs) were employed as the instrumental variantswith three principles. Two-sample Mendelian randomization and transcriptome-wide association (TWAS) analyses were conducted to evaluate the effects of air pollutants on ALS and identify genes associated with both pollutants and ALS, followed by regulatory network prediction.

RESULTS: We observed that exposure to a high level of PM2.5 (OR: 2.40 [95% CI: 1.26-4.57], p = 7.46E-3) and NOx (OR: 2.35 [95% CI: 1.32-4.17], p = 3.65E-3) genetically increased the incidence of ALS in MR analysis, while the effects of NO2 showed a similar trend but without sufficient significance. In the TWAS analysis, TMEM175 and USP35 turned out to be the genes shared between PM2.5 and ALS in the same direction.

CONCLUSION: Higher exposure to PM2.5 and NOX might causally increase the risk of ALS. Avoiding exposure to air pollutants and air cleaning might be necessary for ALS prevention.}, } @article {pmid38969143, year = {2024}, author = {Jha, SK and Nelson, VK and Suryadevara, PR and Panda, SP and Pullaiah, CP and Nuli, MV and Kamal, M and Imran, M and Ausali, S and Abomughaid, MM and Srivastava, R and Deka, R and Pritam, P and Gupta, N and Shyam, H and Singh, IK and Pandey, BW and Dewanjee, S and Jha, NK and Jafari, SM}, title = {Cannabidiol and neurodegeneration: From molecular mechanisms to clinical benefits.}, journal = {Ageing research reviews}, volume = {100}, number = {}, pages = {102386}, doi = {10.1016/j.arr.2024.102386}, pmid = {38969143}, issn = {1872-9649}, mesh = {Humans ; *Cannabidiol/therapeutic use/pharmacology ; *Neurodegenerative Diseases/drug therapy/metabolism ; Animals ; Neuroprotective Agents/therapeutic use/pharmacology ; Oxidative Stress/drug effects ; }, abstract = {Neurodegenerative disorders (NDs) such as Alzheimer's disease, Parkinson's disease, Huntington's disease, multiple sclerosis, and amyotrophic lateral sclerosis are severe and life-threatening conditions in which significant damage of functional neurons occurs to produce psycho-motor malfunctions. NDs are an important cause of death in the elderly population worldwide. These disorders are commonly associated with the progression of age, oxidative stress, and environmental pollutants, which are the major etiological factors. Abnormal aggregation of specific proteins such as α-synuclein, amyloid-β, huntingtin, and tau, and accumulation of the associated oligomers in neurons are the hallmark pathological features of NDs. Existing therapeutic options for NDs are only symptomatic relief and do not address root-causing factors, such as protein aggregation, oxidative stress, and neuroinflammation. Cannabidiol (CBD) is a non-psychotic natural cannabinoid obtained from Cannabis sativa that possesses multiple pharmacological actions, including antioxidant, anti-inflammatory, and neuroprotective effects in various NDs and other neurological disorders both in vitro and in vivo. CBD has gained attention as a promising drug candidate for the management of neurodegenerative disorders, such as Alzheimer's disease and Parkinson's disease, by inhibiting protein aggregation, free radicals, and neuroinflammation. In parallel, CBD has shown positive results in other neurological disorders, such as epilepsy, depression, schizophrenia, and anxiety, as well as adjuvant treatment with existing standard therapeutic agents. Hence, the present review focuses on exploring the possible molecular mechanisms in controlling various neurological disorders as well as the clinical applications of CBD in NDs including epilepsy, depression and anxiety. In this way, the current review will serve as a standalone reference for the researchers working in this area.}, } @article {pmid38968328, year = {2024}, author = {Gowrishankar, S and Smith, ME and Creber, N and Muzaffar, J and Borsetto, D}, title = {Immunosuppression in stem cell clinical trials of neural and retinal cell types: A systematic review.}, journal = {PloS one}, volume = {19}, number = {7}, pages = {e0304073}, pmid = {38968328}, issn = {1932-6203}, mesh = {Humans ; *Stem Cell Transplantation/methods ; *Immunosuppression Therapy/methods ; Retina/immunology ; Immunosuppressive Agents/therapeutic use ; Clinical Trials as Topic ; }, abstract = {BACKGROUND: Pharmacologic immunosuppression regimes are commonly employed in stem cell clinical trials to mitigate host immune rejection and promote survival and viability of transplanted cells. Immunosuppression and cell survival has been extensively studied in retinal and spinal tissues. The applicability of stem cell therapy is rapidly expanding to other sensory organs such as the ear and hearing. As regenerative therapy is directed to new areas, a greater understanding of immunosuppression strategies and their efficacy is required to facilitate translation to organ-specific biologic microenvironments.

OBJECTIVE: This systematic review appraises the current literature regarding immunosuppression strategies employed in stem cell trials of retinal and neural cells.

METHODS: This systematic review was performed in line with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Inclusion criteria included studies presenting data on neural or retinal cells as part of an in-human clinical trial that detailed the immunosuppression regime used. Exclusion criteria included non-English language studies, animal studies, review articles, case reports, editorials, and letters. The databases Medline, Embase, Scopus, Web of Science, and the Cochrane Library were searched from inception to February 2024. Risk of bias was evaluated using the ROBINS-I tool.

RESULTS: Eighteen articles fit the inclusion criteria. Nine articles concerned retinal cells, 5 concerned spinal cord injury, and 4 concerned amyotrophic lateral sclerosis. A multi-drug and short-term immunosuppression regime were commonly employed in the identified studies. Detected immune responses in treated patients were rare. Common immunosuppression paradigms included tacrolimus, mycophenolate mofetil and tapering doses of steroids. Local immunosuppression with steroids was employed in some studies concerning retinal diseases.

DISCUSSION: A short-term course of systemic immunosuppression seemed efficacious for most included studies, with some showing grafted cells viable months to years after immunosuppression had stopped. Longer-term follow-up is required to see if this remains the case. Side effects related to immunosuppression were uncommon.}, } @article {pmid38967881, year = {2024}, author = {Rojas-López, JC and Estrada-Gualdron, PI and Ramírez-Guerrero, S and Velásquez-Cárdenas, MJ and Redondo-Escobar, J and Vargas-Arenas, S and Palacios-Sánchez, L and Palacios-Espinosa, X}, title = {Efficacy of pain management strategies in adults with Amyotrophic Lateral Sclerosis (ALS): A Systematic Review.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {45}, number = {12}, pages = {5591-5604}, pmid = {38967881}, issn = {1590-3478}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/complications/therapy ; *Pain Management/methods ; Adult ; Pain/etiology/drug therapy ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive muscle weakness. Presence of pain in ALS patients is heterogeneously reported in studies, and mostly underrepresented in symptom scales. The aim of this study is to evaluate the efficacy of pharmacological and non-pharmacological therapeutic modalities for pain management in patients with ALS. A systematic review was conducted in four databases; PubMed, Scopus, Clinicaltrials.gov, and Cochrane-Ovid. Five randomized controlled clinical trials were included regarding pharmacological and non-pharmacological pain management interventions in adult patients with confirmed diagnosis of ALS in whom pain was objectively evaluated. Risk of bias assessment was evaluated using the RoB2.0 tool. Eligible studies were reported as a descriptive analysis. This systematic review was registered with PROSPERO ID: CRD42024495009. Five clinical trials regarding pain management strategies in ALS were eligible for analysis. Two out of five were non-pharmacological approaches whilst the remaining three provided pharmacological therapies. Of these, Mexiletine was efficient in terms of pain relief, particularly between 600 and 900 mg per day, whereas Mecasin showed no pain relief at both, high and low doses. Non-pharmacological therapies, such as exercise and osteopathic manual treatment also lacked efficacy in regard to pain management. Clinical trials focusing on pain management strategies for ALS patients are limited. Medical professionals, understandably focused on immediate life-threatening aspects, may inadvertently sideline the nuanced and intricate dimension of pain experienced by patients with ALS.}, } @article {pmid38967655, year = {2024}, author = {Müller, P and Draguhn, A and Egorov, AV}, title = {Persistent sodium currents in neurons: potential mechanisms and pharmacological blockers.}, journal = {Pflugers Archiv : European journal of physiology}, volume = {476}, number = {10}, pages = {1445-1473}, pmid = {38967655}, issn = {1432-2013}, support = {HE8155/1-2//Deutsche Forschungsgemeinschaft/ ; EG134/2-1//Deutsche Forschungsgemeinschaft/ ; Treat-ION01GM1907A//Bundesministerium für Bildung und Forschung/ ; College for Clinician Scientists//Else Kröner-Fresenius-Stiftung/ ; }, mesh = {Humans ; Animals ; *Neurons/metabolism/drug effects/physiology ; Sodium Channel Blockers/pharmacology ; Sodium Channels/metabolism/drug effects ; }, abstract = {Persistent sodium current (INaP) is an important activity-dependent regulator of neuronal excitability. It is involved in a variety of physiological and pathological processes, including pacemaking, prolongation of sensory potentials, neuronal injury, chronic pain and diseases such as epilepsy and amyotrophic lateral sclerosis. Despite its importance, neither the molecular basis nor the regulation of INaP are sufficiently understood. Of particular significance is a solid knowledge and widely accepted consensus about pharmacological tools for analysing the function of INaP and for developing new therapeutic strategies. However, the literature on INaP is heterogeneous, with varying definitions and methodologies used across studies. To address these issues, we provide a systematic review of the current state of knowledge on INaP, with focus on mechanisms and effects of this current in the central nervous system. We provide an overview of the specificity and efficacy of the most widely used INaP blockers: amiodarone, cannabidiol, carbamazepine, cenobamate, eslicarbazepine, ethosuximide, gabapentin, GS967, lacosamide, lamotrigine, lidocaine, NBI-921352, oxcarbazepine, phenytoine, PRAX-562, propofol, ranolazine, riluzole, rufinamide, topiramate, valproaic acid and zonisamide. We conclude that there is strong variance in the pharmacological effects of these drugs, and in the available information. At present, GS967 and riluzole can be regarded bona fide INaP blockers, while phenytoin and lacosamide are blockers that only act on the slowly inactivating component of sodium currents.}, } @article {pmid38967638, year = {2024}, author = {Garau, J and Garofalo, M and Dragoni, F and Scarian, E and Di Gerlando, R and Diamanti, L and Zucca, S and Bordoni, M and Pansarasa, O and Gagliardi, S}, title = {RNA expression profiling in lymphoblastoid cell lines from mutated and non-mutated amyotrophic lateral sclerosis patients.}, journal = {The journal of gene medicine}, volume = {26}, number = {7}, pages = {e3711}, doi = {10.1002/jgm.3711}, pmid = {38967638}, issn = {1521-2254}, support = {//Ministero della Salute/ ; //Italian Agency for Research on ALS-ARiSLA/ ; //Italian Ministry of Health/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics ; *Gene Expression Profiling ; *Mutation ; *Transcriptome ; Female ; Male ; Middle Aged ; C9orf72 Protein/genetics/metabolism ; Leukocytes, Mononuclear/metabolism ; Superoxide Dismutase-1/genetics ; Cell Line ; Aged ; Gene Expression Regulation ; DNA-Binding Proteins ; RNA-Binding Protein FUS ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the death of upper and lower motor neurons with an unknown etiology. The difficulty of recovering biological material from patients led to employ lymphoblastoid cell lines (LCLs) as a model for ALS because many pathways, typically located in neurons, are also activated in these cells.

METHODS: To investigate the expression of coding and long non-coding RNAs in LCLs, a transcriptomic profiling of sporadic ALS (SALS) and mutated patients (FUS, TARDBP, C9ORF72 and SOD1) and matched controls was realized. Thus, differentially expressed genes (DEGs) were investigated among the different subgroups of patients. Peripheral blood mononuclear cells (PBMCs) were isolated and immortalized into LCLs via Epstein-Barr virus infection; RNA was extracted, and RNA-sequencing analysis was performed.

RESULTS: Gene expression profiles of LCLs were genetic-background-specific; indeed, only 12 genes were commonly deregulated in all groups. Nonetheless, pathways enriched by DEGs in each group were also compared, and a total of 89 Kyoto Encyclopedia of Genes and Genomes (KEGG) terms were shared among all patients. Eventually, the similarity of affected pathways was also assessed when our data were matched with a transcriptomic profile realized in the PBMCs of the same patients.

CONCLUSIONS: We conclude that LCLs are a good model for the study of RNA deregulation in ALS.}, } @article {pmid38967302, year = {2024}, author = {Sîrbulescu, RF and Nicholson, K and Kawai, K and Hilton, OM and Sobell, D and Jin, G and Verrill, DE and Dwyer, LJ and Xiong, Y and Bachanová, P and Kim, SE and Gallup, S and Gelevski, D and Daley, H and Hernandez Rodriguez, DE and Negre, H and Sturtevant, O and Nikiforow, S and Ritz, J and Chen, YB and Reeves, PM and Sluder, AE and Berry, JD and Sadri-Vakili, G and Cudkowicz, M and Poznansky, MC}, title = {Allogeneic B cell immunomodulatory therapy in amyotrophic lateral sclerosis.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {38}, number = {13}, pages = {e23796}, doi = {10.1096/fj.202302659R}, pmid = {38967302}, issn = {1530-6860}, support = {//Ward Family Foundation/ ; //Vaccine and Immunotherapy Center Innovation Fund/ ; //Vaccine and Immunotherapy Center Education Fund/ ; //Sean M. Healey and AMG Center for ALS/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/therapy/immunology ; Animals ; Mice ; Humans ; *B-Lymphocytes/immunology ; Disease Models, Animal ; Mice, Transgenic ; Male ; Female ; Mice, Inbred C57BL ; Immunomodulation ; Middle Aged ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is an orphan neurodegenerative disease. Immune system dysregulation plays an essential role in ALS onset and progression. Our preclinical studies have shown that the administration of exogenous allogeneic B cells improves outcomes in murine models of skin and brain injury through a process termed pligodraxis, in which B cells adopt an immunoregulatory and neuroprotective phenotype in an injured environment. Here, we investigated the effects of B-cell therapy in the SOD1[G93A] mouse preclinical model of ALS and in a person living with ALS. Purified splenic mature naïve B cells from haploidentical donor mice were administered intravenously in SOD1[G93A] mice for a total of 10 weekly doses. For the clinical study in a person with advanced ALS, IgA gammopathy of unclear significance, and B lymphopenia, CD19[+] B cells were positively selected from a healthy haploidentical donor and infused intravenously twice, at a 60-day interval. Repeated intravenous B-cell administration was safe and significantly delayed disease onset, extended survival, reduced cellular apoptosis, and decreased astrogliosis in SOD1[G93A] mice. Repeated B-cell infusion in a person with ALS was safe and did not appear to generate a clinically evident inflammatory response. An improvement of 5 points on the ALSFRS-R scale was observed after the first infusion. Levels of inflammatory markers showed persistent reduction post-infusion. This represents a first demonstration of the efficacy of haploidentical B-cell infusion in the SOD1[G93A] mouse and the safety and feasibility of using purified haploidentical B lymphocytes as a cell-based therapeutic strategy for a person with ALS.}, } @article {pmid38967083, year = {2024}, author = {Nijs, M and Van Damme, P}, title = {The genetics of amyotrophic lateral sclerosis.}, journal = {Current opinion in neurology}, volume = {37}, number = {5}, pages = {560-569}, pmid = {38967083}, issn = {1473-6551}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/diagnosis ; *C9orf72 Protein/genetics ; *Genetic Predisposition to Disease/genetics ; *RNA-Binding Protein FUS/genetics ; Superoxide Dismutase-1/genetics ; Superoxide Dismutase/genetics ; Proteins/genetics ; DNA-Binding Proteins/genetics ; Genetic Testing ; }, abstract = {PURPOSE OF REVIEW: Amyotrophic lateral sclerosis (ALS) has a strong genetic basis, but the genetic landscape of ALS appears to be complex. The purpose of this article is to review recent developments in the genetics of ALS.

RECENT FINDINGS: Large-scale genetic studies have uncovered more than 40 genes contributing to ALS susceptibility. Both rare variants with variable effect size and more common variants with small effect size have been identified. The most common ALS genes are C9orf72 , SOD1 , TARDBP and FUS . Some of the causative genes of ALS are shared with frontotemporal dementia, confirming the molecular link between both diseases. Access to diagnostic gene testing for ALS has to improve, as effective gene silencing therapies for some genetic subtypes of ALS are emerging, but there is no consensus about which genes to test for.

SUMMARY: Our knowledge about the genetic basis of ALS has improved and the first effective gene silencing therapies for specific genetic subtypes of ALS are underway. These therapeutic advances underline the need for better access to gene testing for people with ALS. Further research is needed to further map the genetic heterogeneity of ALS and to establish the best strategy for gene testing in a clinical setting.}, } @article {pmid38966756, year = {2024}, author = {Garg, V and Geurten, BRH}, title = {Diving deep: zebrafish models in motor neuron degeneration research.}, journal = {Frontiers in neuroscience}, volume = {18}, number = {}, pages = {1424025}, pmid = {38966756}, issn = {1662-4548}, abstract = {In the dynamic landscape of biomedical science, the pursuit of effective treatments for motor neuron disorders like hereditary spastic paraplegia (HSP), amyotrophic lateral sclerosis (ALS), and spinal muscular atrophy (SMA) remains a key priority. Central to this endeavor is the development of robust animal models, with the zebrafish emerging as a prime candidate. Exhibiting embryonic transparency, a swift life cycle, and significant genetic and neuroanatomical congruencies with humans, zebrafish offer substantial potential for research. Despite the difference in locomotion-zebrafish undulate while humans use limbs, the zebrafish presents relevant phenotypic parallels to human motor control disorders, providing valuable insights into neurodegenerative diseases. This review explores the zebrafish's inherent traits and how they facilitate profound insights into the complex behavioral and cellular phenotypes associated with these disorders. Furthermore, we examine recent advancements in high-throughput drug screening using the zebrafish model, a promising avenue for identifying therapeutically potent compounds.}, } @article {pmid38966655, year = {2024}, author = {Saito, S and Ikeguchi, R and Kitagawa, K}, title = {Chronic cerebrospinal fluid leak can cause amyotrophic lateral sclerosis mimic.}, journal = {Journal of general and family medicine}, volume = {25}, number = {4}, pages = {237-238}, pmid = {38966655}, issn = {2189-7948}, abstract = {Chronic cerebrospinal fluid leak with spinal cord compression can mimic the symptoms of ALS, with a snake-eyes appearance on MRI.}, } @article {pmid38966427, year = {2024}, author = {Couturier, N and Hörner, SJ and Nürnberg, E and Joazeiro, C and Hafner, M and Rudolf, R}, title = {Aberrant evoked calcium signaling and nAChR cluster morphology in a SOD1 D90A hiPSC-derived neuromuscular model.}, journal = {Frontiers in cell and developmental biology}, volume = {12}, number = {}, pages = {1429759}, pmid = {38966427}, issn = {2296-634X}, abstract = {Familial amyotrophic lateral sclerosis (ALS) is a progressive neuromuscular disorder that is due to mutations in one of several target genes, including SOD1. So far, clinical records, rodent studies, and in vitro models have yielded arguments for either a primary motor neuron disease, or a pleiotropic pathogenesis of ALS. While mouse models lack the human origin, in vitro models using human induced pluripotent stem cells (hiPSC) have been recently developed for addressing ALS pathogenesis. In spite of improvements regarding the generation of muscle cells from hiPSC, the degree of maturation of muscle cells resulting from these protocols has remained limited. To fill these shortcomings, we here present a new protocol for an enhanced myotube differentiation from hiPSC with the option of further maturation upon coculture with hiPSC-derived motor neurons. The described model is the first to yield a combination of key myogenic maturation features that are consistent sarcomeric organization in association with complex nAChR clusters in myotubes derived from control hiPSC. In this model, myotubes derived from hiPSC carrying the SOD1 D90A mutation had reduced expression of myogenic markers, lack of sarcomeres, morphologically different nAChR clusters, and an altered nAChR-dependent Ca[2+] response compared to control myotubes. Notably, trophic support provided by control hiPSC-derived motor neurons reduced nAChR cluster differences between control and SOD1 D90A myotubes. In summary, a novel hiPSC-derived neuromuscular model yields evidence for both muscle-intrinsic and nerve-dependent aspects of neuromuscular dysfunction in SOD1-based ALS.}, } @article {pmid38965709, year = {2024}, author = {Arends, S and Drenthen, J and de Koning, L and van den Bergh, P and Hadden, RDM and Kuwabara, S and Reisin, RC and Shahrizaila, N and Ajroud-Driss, S and Antonini, G and Attarian, S and Balducci, C and Bertorini, T and Brannagan, TH and Cavaletti, G and Chao, CC and Chavada, G and Dillmann, KU and Dimachkie, MM and Galassi, G and Gutiérrez-Gutiérrez, G and Harbo, T and Islam, B and Islam, Z and Katzberg, H and Kusunoki, S and Manganelli, F and Miller, JAL and Pardo, J and Pereon, Y and Rajabally, YA and Sindrup, S and Stettner, M and Uncini, A and Verhamme, C and Vytopil, M and Waheed, W and Jacobs, BC and Cornblath, DR and , }, title = {Electrodiagnostic subtyping in Guillain-Barré syndrome patients in the International Guillain-Barré Outcome Study.}, journal = {European journal of neurology}, volume = {31}, number = {9}, pages = {e16335}, pmid = {38965709}, issn = {1468-1331}, mesh = {Humans ; *Guillain-Barre Syndrome/diagnosis/classification/physiopathology ; *Neural Conduction/physiology ; *Electrodiagnosis/methods ; Male ; Female ; Middle Aged ; Adult ; Amyotrophic Lateral Sclerosis/diagnosis/classification/physiopathology ; Aged ; Cohort Studies ; }, abstract = {BACKGROUND AND PURPOSE: Various electrodiagnostic criteria have been developed in Guillain-Barré syndrome (GBS). Their performance in a broad representation of GBS patients has not been evaluated. Motor conduction data from the International GBS Outcome Study (IGOS) cohort were used to compare two widely used criterion sets and relate these to diagnostic amyotrophic lateral sclerosis criteria.

METHODS: From the first 1500 patients in IGOS, nerve conduction studies from 1137 (75.8%) were available for the current study. These patients were classified according to nerve conduction studies criteria proposed by Hadden and Rajabally.

RESULTS: Of the 1137 studies, 68.3% (N = 777) were classified identically according to criteria by Hadden and Rajabally: 111 (9.8%) axonal, 366 (32.2%) demyelinating, 195 (17.2%) equivocal, 35 (3.1%) inexcitable and 70 (6.2%) normal. Thus, 360 studies (31.7%) were classified differently. The areas of differences were as follows: 155 studies (13.6%) classified as demyelinating by Hadden and axonal by Rajabally; 122 studies (10.7%) classified as demyelinating by Hadden and equivocal by Rajabally; and 75 studies (6.6%) classified as equivocal by Hadden and axonal by Rajabally. Due to more strictly defined cutoffs fewer patients fulfilled demyelinating criteria by Rajabally than by Hadden, making more patients eligible for axonal or equivocal classification by Rajabally. In 234 (68.6%) axonal studies by Rajabally the revised El Escorial (amyotrophic lateral sclerosis) criteria were fulfilled; in axonal cases by Hadden this was 1.8%.

CONCLUSIONS AND DISCUSSION: This study shows that electrodiagnosis in GBS is dependent on the criterion set utilized, both of which are based on expert opinion. Reappraisal of electrodiagnostic subtyping in GBS is warranted.}, } @article {pmid38965379, year = {2024}, author = {Jacob, SM and Lee, S and Kim, SH and Sharkey, KA and Pfeffer, G and Nguyen, MD}, title = {Brain-body mechanisms contribute to sexual dimorphism in amyotrophic lateral sclerosis.}, journal = {Nature reviews. Neurology}, volume = {20}, number = {8}, pages = {475-494}, pmid = {38965379}, issn = {1759-4766}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/physiopathology/epidemiology/metabolism ; *Sex Characteristics ; Male ; Female ; Animals ; Brain/metabolism/physiopathology ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is the most common form of human motor neuron disease. It is characterized by the progressive degeneration of upper and lower motor neurons, leading to generalized motor weakness and, ultimately, respiratory paralysis and death within 3-5 years. The disease is shaped by genetics, age, sex and environmental stressors, but no cure or routine biomarkers exist for the disease. Male individuals have a higher propensity to develop ALS, and a different manifestation of the disease phenotype, than female individuals. However, the mechanisms underlying these sex differences remain a mystery. In this Review, we summarize the epidemiology of ALS, examine the sexually dimorphic presentation of the disease and highlight the genetic variants and molecular pathways that might contribute to sex differences in humans and animal models of ALS. We advance the idea that sexual dimorphism in ALS arises from the interactions between the CNS and peripheral organs, involving vascular, metabolic, endocrine, musculoskeletal and immune systems, which are strikingly different between male and female individuals. Finally, we review the response to treatments in ALS and discuss the potential to implement future personalized therapeutic strategies for the disease.}, } @article {pmid38964584, year = {2024}, author = {Peters, S and Bouma, F and Hoek, G and Janssen, N and Vermeulen, R}, title = {Air pollution exposure and mortality from neurodegenerative diseases in the Netherlands: A population-based cohort study.}, journal = {Environmental research}, volume = {259}, number = {}, pages = {119552}, doi = {10.1016/j.envres.2024.119552}, pmid = {38964584}, issn = {1096-0953}, mesh = {Humans ; Netherlands/epidemiology ; *Air Pollution/adverse effects/analysis ; Male ; *Air Pollutants/analysis/adverse effects ; *Neurodegenerative Diseases/mortality/chemically induced/epidemiology ; Middle Aged ; Female ; Cohort Studies ; *Environmental Exposure/adverse effects ; Aged ; *Particulate Matter/analysis/adverse effects ; Adult ; }, abstract = {BACKGROUND: Long-term exposure to ambient air pollution has been linked with all-cause mortality and cardiovascular and respiratory diseases. Suggestive associations between ambient air pollutants and neurodegeneration have also been reported, but due to the small effect and relatively rare outcomes evidence is yet inconclusive. Our aim was to investigate the associations between long-term air pollution exposure and mortality from neurodegenerative diseases.

METHODS: A Dutch national cohort of 10.8 million adults aged ≥30 years was followed from 2013 until 2019. Annual average concentrations of air pollutants (ultra-fine particles (UFP), nitrogen dioxide (NO2), fine particles (PM2.5 and PM10) and elemental carbon (EC)) were estimated at the home address at baseline, using land-use regression models. The outcome variables were mortality due to amyotrophic lateral sclerosis (ALS), Parkinson's disease, non-vascular dementia, Alzheimer's disease, and multiple sclerosis (MS). Hazard ratios (HR) were estimated using Cox models, adjusting for individual and area-level socio-economic status covariates.

RESULTS: We had a follow-up of 71 million person-years. The adjusted HRs for non-vascular dementia were significantly increased for NO2 (1.03; 95% confidence interval (CI) 1.02-1.05) and PM2.5 (1.02; 95%CI 1.01-1.03) per interquartile range (IQR; 6.52 and 1.47 μg/m[3], respectively). The association with PM2.5 was also positive for ALS (1.02; 95%CI 0.97-1.07). These associations remained positive in sensitivity analyses and two-pollutant models. UFP was not associated with any outcome. No association with air pollution was found for Parkinson's disease and MS. Inverse associations were found for Alzheimer's disease.

CONCLUSION: Our findings, using a cohort of more than 10 million people, provide further support for associations between long-term exposure to air pollutants (PM2.5 and particularly NO2) and mortality of non-vascular dementia. No associations were found for Parkinson and MS and an inverse association was observed for Alzheimer's disease.}, } @article {pmid38963716, year = {2024}, author = {Lima, PLGSB and Couto, EM and Nóbrega, PR}, title = {Response letter to: a homozygous p.Val120Leu (c.358G > C) SOD1 mutation led to slowly progressive amyotrophic lateral sclerosis in a Brazilian family.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {25}, number = {7-8}, pages = {803-804}, doi = {10.1080/21678421.2024.2374372}, pmid = {38963716}, issn = {2167-9223}, } @article {pmid38963497, year = {2024}, author = {Yu, G and Bai, Y and Zhang, ZY}, title = {Valosin-Containing Protein (VCP)/p97 Oligomerization.}, journal = {Sub-cellular biochemistry}, volume = {104}, number = {}, pages = {485-501}, pmid = {38963497}, issn = {0306-0225}, mesh = {*Valosin Containing Protein/metabolism/genetics/chemistry ; Humans ; Protein Multimerization ; Animals ; Mutation ; Frontotemporal Dementia/genetics/metabolism ; Adenosine Triphosphatases/metabolism/genetics/chemistry ; Osteitis Deformans/genetics/metabolism ; Cell Cycle Proteins/metabolism/genetics/chemistry ; Myositis, Inclusion Body/genetics/metabolism ; Muscular Dystrophies, Limb-Girdle ; }, abstract = {Valosin-containing protein (VCP), also known as p97, is an evolutionarily conserved AAA+ ATPase essential for cellular homeostasis. Cooperating with different sets of cofactors, VCP is involved in multiple cellular processes through either the ubiquitin-proteasome system (UPS) or the autophagy/lysosomal route. Pathogenic mutations frequently found at the interface between the NTD domain and D1 ATPase domain have been shown to cause malfunction of VCP, leading to degenerative disorders including the inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia (IBMPFD), amyotrophic lateral sclerosis (ALS), and cancers. Therefore, VCP has been considered as a potential therapeutic target for neurodegeneration and cancer. Most of previous studies found VCP predominantly exists and functions as a hexamer, which unfolds and extracts ubiquitinated substrates from protein complexes for degradation. However, recent studies have characterized a new VCP dodecameric state and revealed a controlling mechanism of VCP oligomeric states mediated by the D2 domain nucleotide occupancy. Here, we summarize our recent knowledge on VCP oligomerization, regulation, and potential implications of VCP in cellular function and pathogenic progression.}, } @article {pmid38963135, year = {2024}, author = {Turano, E and Virla, F and Scambi, I and Dabrowska, S and Bankole, O and Mariotti, R}, title = {Adipose mesenchymal stem cells-derived extracellular vesicles exert their preferential action in damaged central sites of SOD1 mice rather than peripherally.}, journal = {European journal of histochemistry : EJH}, volume = {68}, number = {3}, pages = {}, pmid = {38963135}, issn = {2038-8306}, mesh = {Animals ; *Extracellular Vesicles/metabolism ; *Mesenchymal Stem Cells/metabolism ; Mice ; *Amyotrophic Lateral Sclerosis/metabolism/therapy/pathology ; *Superoxide Dismutase-1/genetics/metabolism ; Mice, Transgenic ; Disease Models, Animal ; Adipose Tissue/metabolism ; Motor Neurons/metabolism ; Neuromuscular Junction/metabolism ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder involving motor neuron (MN) loss in the motor cortex, brainstem and spinal cord leading to progressive paralysis and death. Due to the pathogenetic complexity, there are no effective therapies available. In this context the use of mesenchymal stem cells and their vesicular counterpart is an emerging therapeutic strategy to counteract neurodegeneration. The extracellular vesicles derived from adipose stem cells (ASC-EVs) recapitulate and ameliorate the neuroprotective effect of stem cells and, thanks to their small dimensions, makes their use suitable to develop novel therapeutic approaches for neurodegenerative diseases as ALS. Here we investigate a therapeutic regimen of ASC-EVs injection in SOD1(G93A) mice, the most widely used murine model of ALS. Repeated intranasal administrations of high doses of ASC-EVs were able to ameliorate motor performance of injected SOD1(G93A) mice at the early stage of the disease and produce a significant improvement at the end-stage in the lumbar MNs rescue. Moreover, ASC-EVs preserve the structure of neuromuscular junction without counteracting the muscle atrophy. The results indicate that the intranasal ASC-EVs administration acts in central nervous system sites rather than at peripheral level in SOD1(G93A) mice. These considerations allow us to identify future applications of ASC-EVs that involve different targets simultaneously to maximize the clinical and neuropathological outcomes in ALS in vivo models.}, } @article {pmid38963090, year = {2024}, author = {Pearson, K and Dobak, S}, title = {Current practices in the nutrition management of people with amyotrophic lateral sclerosis (ALS): a survey of U.S. ALS care teams.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {25}, number = {7-8}, pages = {653-660}, doi = {10.1080/21678421.2024.2374382}, pmid = {38963090}, issn = {2167-9223}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diet therapy ; Cross-Sectional Studies ; United States/epidemiology ; Male ; Patient Care Team ; Female ; Surveys and Questionnaires ; Nutrition Therapy/methods ; Nutritionists/statistics & numerical data ; }, abstract = {OBJECTIVE: To assess current practices of U.S. professionals providing outpatient ALS nutrition care.

METHODS: A cross-sectional survey assessing nutrition care practices was distributed in February/March 2023 through electronic mailing lists of relevant professional organizations.

RESULTS: Of the 87 professionals completing the survey, 85.1% were registered dietitians and 50.6% had five or fewer years of experience in ALS care. Many (44.2%) professionals reported receiving no training on the nutrition care of people with ALS (PALS), and 40.2% reported having no other ALS dietitians in their close network. Methods utilized to estimate calorie and protein requirements in PALS varied widely. Although 95.4% of respondents reported that their clinic's dietitian participates in feeding tube discussions, many practitioners may be waiting until ALS symptoms negatively impact PALS' breathing, eating, swallowing, or weight to begin discussing feeding tubes. Additionally, few professionals reported institutional practices conducive for refeeding syndrome prevention or monitoring.

CONCLUSIONS: Many professionals providing outpatient nutrition care to PALS possess limited experience, received insufficient training, and are not connected to other ALS dietitians. Specific nutrition care practices, including nutrient need estimation, vary widely among health professionals. Practices surrounding feeding tube discussions and refeeding syndrome may be suboptimal at many institutions. These findings highlight the need for initiatives that educate and connect practitioners providing nutrition care to PALS.}, } @article {pmid38963079, year = {2024}, author = {Naruse, H and Iseki, C and Mitsui, J and Miki, J and Nagasawa, H and Kurokawa, K and Kobayashi, R and Sato, H and Goto, J and Satake, W and Ishiura, H and Tsuji, S and Ohta, Y and Toda, T}, title = {A novel TBK1 loss-of-function variant associated with ALS and parkinsonism phenotypes.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {25}, number = {7-8}, pages = {791-794}, doi = {10.1080/21678421.2024.2374374}, pmid = {38963079}, issn = {2167-9223}, mesh = {Humans ; *Protein Serine-Threonine Kinases/genetics ; *Amyotrophic Lateral Sclerosis/genetics/diagnosis ; *Parkinsonian Disorders/genetics ; Male ; Female ; Middle Aged ; *Phenotype ; Loss of Function Mutation/genetics ; Pedigree ; Aged ; Adult ; }, abstract = {Loss-of-function (LoF) variants in the TANK binding kinase 1 (TBK1) gene are implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. In this study, we present the first familial cases of ALS and parkinsonism associated with a novel TBK1 variant. We describe two siblings: one diagnosed with classical ALS and the other with a unique syndrome overlapping ALS and parkinsonism. Comprehensive clinical and imaging evaluations supported these diagnoses. Genetic analysis through whole-genome sequencing revealed a previously unknown heterozygous splice site variant in TBK1. Functional assessments demonstrated that this splice site variant leads to abnormal splicing and subsequent degradation of the mutated TBK1 allele by nonsense-mediated decay, confirming its pathogenic impact. Our findings suggest a broader involvement of TBK1 in neurodegenerative diseases and underscore the need for further research into TBK1's role, advocating for screening for TBK1 variants in similar familial cases.}, } @article {pmid38961496, year = {2024}, author = {Linse, K and Weber, C and Reilich, P and Schöberl, F and Boentert, M and Petri, S and Rödiger, A and Posa, A and Otto, M and Wolf, J and Zeller, D and Brunkhorst, R and Koch, J and Hermann, A and Großkreutz, J and Schröter, C and Groß, M and Lingor, P and Machetanz, G and Semmler, L and Dorst, J and Lulé, D and Ludolph, A and Meyer, T and Maier, A and Metelmann, M and Regensburger, M and Winkler, J and Schrank, B and Kohl, Z and Hagenacker, T and Brakemeier, S and Weyen, U and Weiler, M and Lorenzl, S and Bublitz, S and Weydt, P and Grehl, T and Kotterba, S and Lapp, HS and Freigang, M and Vidovic, M and Aust, E and Günther, R}, title = {Patients' and caregivers' perception of multidimensional and palliative care in amyotrophic lateral sclerosis - protocol of a German multicentre study.}, journal = {Neurological research and practice}, volume = {6}, number = {1}, pages = {34}, pmid = {38961496}, issn = {2524-3489}, abstract = {INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is an inevitably fatal condition that leads to a progressive loss of physical functioning, which results in a high psychosocial burden and organizational challenges related to medical care. Multidimensional and multiprofessional care is advised to meet the complex needs of patients and their families. Many healthcare systems, including Germany, may not be able to meet these needs because non-medical services such as psychological support or social counselling are not regularly included in the care of patients with ALS (pwALS). Specialised neuropalliative care is not routinely implemented nor widely available. Caregivers of pwALS are also highly burdened, but there is still a lack of support services for them.

METHODS: This project aims to assess the perceptions and satisfaction with ALS care in Germany in pwALS and their caregivers. This will be achieved by means of a cross-sectional, multicentre survey. The examination will assess, to which extend the patients' needs in the six domains of physical, psychological, social, spiritual, practical and informational are being met by current care structures. This assessment will be linked to mental well-being, subjective quality of life, attitudes toward life-sustaining measures and physician-assisted suicide, and caregiver burden. The study aims to recruit 500 participants from nationwide ALS centres in order to draw comprehensive conclusions for Germany. A total of 29 centres, mostly acquired via the clinical and scientific German Network for Motor Neuron Diseases (MND-NET), will take part in the project, 25 of which have already started recruitment.

PERSPECTIVE: It is intended to provide data-based starting points on how current practice of care in Germany is perceived pwALS and their caregivers and how it can be improved according to their needs. Planning and initiation of the study has been completed.

TRIAL REGISTRATION: The study is registered at ClinicalTrails.gov; NCT06418646.}, } @article {pmid38960585, year = {2025}, author = {Dols-Icardo, O and Carbayo, Á and Jericó, I and Blasco-Martínez, O and Álvarez-Sánchez, E and López Pérez, MA and Bernal, S and Rodríguez-Santiago, B and Cusco, I and Turon-Sans, J and Cabezas-Torres, M and Caballero-Ávila, M and Vesperinas, A and Llansó, L and Pagola-Lorz, I and Torné, L and Valle-Tamayo, N and Muñoz, L and Rubio-Guerra, S and Illán-Gala, I and Cortés-Vicente, E and Gelpi, E and Rojas-García, R}, title = {Identification of a pathogenic mutation in ARPP21 in patients with amyotrophic lateral sclerosis.}, journal = {Journal of neurology, neurosurgery, and psychiatry}, volume = {96}, number = {2}, pages = {132-139}, pmid = {38960585}, issn = {1468-330X}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/epidemiology ; Male ; Female ; Middle Aged ; Spain/epidemiology ; Aged ; *Phosphoproteins/genetics ; *Mutation, Missense/genetics ; Adult ; Pedigree ; Genetic Predisposition to Disease ; Whole Genome Sequencing ; }, abstract = {BACKGROUND AND OBJECTIVE: Between 5% and 10% of amyotrophic lateral sclerosis (ALS) cases have a family history of the disease, 30% of which do not have an identifiable underlying genetic cause after a comprehensive study of the known ALS-related genes. Based on a significantly increased incidence of ALS in a small geographical region from Spain, the aim of this work was to identify novel ALS-related genes in ALS cases with negative genetic testing.

METHODS: We detected an increased incidence of both sporadic and, especially, familial ALS cases in a small region from Spain compared with available demographic and epidemiological data. We performed whole genome sequencing in a group of 12 patients with ALS (5 of them familial) from this unique area. We expanded the study to include affected family members and additional cases from a wider surrounding region.

RESULTS: We identified a shared missense mutation (c.1586C>T; p.Pro529Leu) in the cyclic AMP regulated phosphoprotein 21 (ARPP21) gene that encodes an RNA-binding protein, in a total of 10 patients with ALS from 7 unrelated families. No mutations were found in other ALS-causing genes.

CONCLUSIONS: While previous studies have dismissed a causal role of ARPP21 in ALS, our results strongly support ARPP21 as a novel ALS-causing gene.}, } @article {pmid38960473, year = {2024}, author = {R, HC and Datta, A and S, UK and Zayed, H and D, TK and C, GPD}, title = {Decoding genetic and pathophysiological mechanisms in amyotrophic lateral sclerosis and primary lateral sclerosis: A comparative study of differentially expressed genes and implicated pathways in motor neuron disorders.}, journal = {Advances in protein chemistry and structural biology}, volume = {141}, number = {}, pages = {177-201}, doi = {10.1016/bs.apcsb.2023.12.008}, pmid = {38960473}, issn = {1876-1631}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/metabolism ; Gene Expression Profiling ; Motor Neuron Disease/genetics/metabolism ; }, abstract = {Motor Neuron Disorders (MNDs), characterized by the degradation and loss of function of motor neurons, are recognized as fatal conditions with limited treatment options and no known cure. The present study aimed to identify the pathophysiological functions and affected genes in patients with MNDs, specifically Amyotrophic Lateral Sclerosis (ALS) and Primary Lateral Sclerosis (PLS). The GSE56808 dataset comprised three sample groups: six patients diagnosed with ALS (GSM1369650, GSM1369652, GSM1369654, GSM1369656, GSM1369657, GSM1369658), five patients diagnosed with PLS (GSM1369648, GSM1369649, GSM1369653, GSM1369655, GSM1369659), and six normal controls (GSM1369642, GSM1369643, GSM1369644, GSM1369645, GSM1369646, and GSM1369647). The application of computational analysis of microarray gene expression profiles enabled us to identify 346 significantly differentially expressed genes (DEGs), 169 genes for the ALS sample study, and 177 genes for the PLS sample study. Enrichment was carried out using MCODE, a Cytoscape plugin. Functional annotation of DEGs was carried out via ClueGO/CluePedia (v2.5.9) and further validated via the DAVID database. NRP2, SEMA3D, ROBO3 and, CACNB1, CACNG2 genes were identified as the gene of interest for ALS and PLS sample groups, respectively. Axonal guidance (GO:0007411) and calcium ion transmembrane transport (GO:0070588) were identified to be some of the significantly dysregulated gene ontology (GO) terms, with arrhythmogenic right ventricular cardiomyopathy (KEGG:05412) to be the top relevant KEGG pathway which is affected in MND patients. ROBO3 gene was observed to have distinctive roles in ALS and PLS-affected patients, hinting towards the differential progression of ALS from PLS. The insights derived from our comprehensive analysis accentuate the distinct variances in the underlying molecular pathogenesis of ALS and PLS. Further research should investigate the mechanistic roles of the identified DEGs and molecular pathways, leading to potential targeted therapies for ALS and PLS.}, } @article {pmid38960099, year = {2024}, author = {Bhandari, UR and Danish, SM and Ahmad, S and Ikram, M and Nadaf, A and Hasan, N and Kesharwani, P and Ahmad, FJ}, title = {New opportunities for antioxidants in amelioration of neurodegenerative diseases.}, journal = {Mechanisms of ageing and development}, volume = {221}, number = {}, pages = {111961}, doi = {10.1016/j.mad.2024.111961}, pmid = {38960099}, issn = {1872-6216}, mesh = {Humans ; *Antioxidants/pharmacology/therapeutic use ; *Neurodegenerative Diseases/metabolism/drug therapy ; *Oxidative Stress/drug effects ; Animals ; Neuroprotective Agents/pharmacology/therapeutic use ; Signal Transduction/drug effects ; Reactive Oxygen Species/metabolism ; }, abstract = {This comprehensive review elucidates the critical role of antioxidants to mitigate oxidative stress, a common denominator in an array of neurodegenerative disorders. Oxidative stress-induced damage has been linked to the development of diseases such as Alzheimer's, Parkinson's, Huntington's disease and amyotrophic lateral sclerosis. This article examines a wide range of scientific literature and methodically delineates the several methods by which antioxidants exercise their neuroprotective benefits. It also explores into the complex relationship between oxidative stress and neuroinflammation, focusing on how antioxidants can alter signaling pathways and transcription factors to slow neurodegenerative processes. Key antioxidants, such as vitamins C and E, glutathione, and polyphenolic compounds, are tested for their ability to combat reactive oxygen and nitrogen species. The dual character of antioxidants, which operate as both direct free radical scavengers and regulators of cellular redox homeostasis, is investigated in terms of therapeutic potential. Furthermore, the study focuses on new antioxidant-based therapy techniques and their mechanisms including Nrf-2, PCG1α, Thioredoxin etc., which range from dietary interventions to targeted antioxidant molecules. Insights into ongoing clinical studies evaluating antioxidant therapies in neurodegenerative illnesses offer an insight into the translational potential of antioxidant research. Finally, this review summarizes our present understanding of antioxidant processes in neurodegenerative illnesses, providing important possibilities for future study and treatment development.}, } @article {pmid38958608, year = {2024}, author = {Lang, R and Hodgson, RE and Shelkovnikova, TA}, title = {TDP-43 in nuclear condensates: where, how, and why.}, journal = {Biochemical Society transactions}, volume = {52}, number = {4}, pages = {1809-1825}, pmid = {38958608}, issn = {1470-8752}, mesh = {Humans ; *DNA-Binding Proteins/metabolism ; *Cell Nucleus/metabolism ; *Amyotrophic Lateral Sclerosis/metabolism ; Biomolecular Condensates/metabolism ; Animals ; Neurodegenerative Diseases/metabolism ; }, abstract = {TDP-43 is an abundant and ubiquitously expressed nuclear protein that becomes dysfunctional in a spectrum of neurodegenerative diseases. TDP-43's ability to phase separate and form/enter biomolecular condensates of varying size and composition is critical for its functionality. Despite the high density of phase-separated assemblies in the nucleus and the nuclear abundance of TDP-43, our understanding of the condensate-TDP-43 relationship in this cellular compartment is only emerging. Recent studies have also suggested that misregulation of nuclear TDP-43 condensation is an early event in the neurodegenerative disease amyotrophic lateral sclerosis. This review aims to draw attention to the nuclear facet of functional and aberrant TDP-43 condensation. We will summarise the current knowledge on how TDP-43 containing nuclear condensates form and function and how their homeostasis is affected in disease.}, } @article {pmid38958573, year = {2024}, author = {Tu, S and Vucic, S and Kiernan, MC}, title = {Pathological insights derived from neuroimaging in amyotrophic lateral sclerosis: emerging clinical applications.}, journal = {Current opinion in neurology}, volume = {37}, number = {5}, pages = {577-584}, doi = {10.1097/WCO.0000000000001295}, pmid = {38958573}, issn = {1473-6551}, mesh = {*Amyotrophic Lateral Sclerosis/diagnostic imaging/pathology ; Humans ; *Neuroimaging/methods ; Brain/diagnostic imaging/pathology ; }, abstract = {PURPOSE OF REVIEW: Neuroimaging has been instrumental in shaping current understanding of the pathoanatomical signature of amyotrophic lateral sclerosis (ALS) across clinically well defined patient cohorts. The potential utility of imaging as an objective disease marker, however, remains poorly defined.

RECENT FINDINGS: Increasingly advanced quantitative and computational imaging studies have highlighted emerging clinical applications for neuroimaging as a complementary clinical modality for diagnosis, monitoring, and modelling disease propagation. Multimodal neuroimaging has demonstrated novel approaches for capturing primary motor disease. Extra-motor subcortical dysfunction is increasingly recognized as key modulators of disease propagation.

SUMMARY: The neural signature of cortical and subcortical dysfunction in ALS has been well defined at the population level. Objective metrics of focal primary motor dysfunction are increasingly sensitive and translatable to the individual patient level. Integrity of extra-motor subcortical abnormalities are recognized to represent critical pathways of the ALS disease 'connectome', predicting pathological spread. Neuroimaging plays a pivotal role in capturing upper motor neuron pathology in ALS. Their potential clinical role as objective disease markers for disease classification, longitudinal monitoring, and prognosis in ALS have become increasingly well defined.}, } @article {pmid38957123, year = {2025}, author = {Ghaderi, S and Fatehi, F and Kalra, S and Mohammadi, S and Batouli, SAH}, title = {Quantitative susceptibility mapping in amyotrophic lateral sclerosis: automatic quantification of the magnetic susceptibility in the subcortical nuclei.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {26}, number = {1-2}, pages = {73-84}, doi = {10.1080/21678421.2024.2372648}, pmid = {38957123}, issn = {2167-9223}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnostic imaging ; Male ; Female ; Middle Aged ; *Magnetic Resonance Imaging/methods ; Adult ; *Brain Mapping/methods ; Subthalamic Nucleus/diagnostic imaging ; Aged ; }, abstract = {OBJECTIVE: Previous studies have suggested a link between dysregulation of cortical iron levels and neuronal loss in amyotrophic lateral sclerosis (ALS) patients. However, few studies have reported differences in quantitative susceptibility mapping (QSM) values in subcortical nuclei between patients with ALS and healthy controls (HCs).

METHODS: MRI was performed using a 3 Tesla Prisma scanner (64-channel head coil), including 3D T1-MPRAGE and multi-echo 3D GRE for QSM reconstruction. Automated QSM segmentation was used to measure susceptibility values in the subcortical nuclei, which were compared between the groups. Correlations with clinical scales were analyzed. Group comparisons were performed using independent t-tests, with p < 0.05 considered significant. Correlations were assessed using Pearson's correlation, with p < 0.05 considered significant. Cohen's d was reported to compare the standardized mean difference (SMD) of QSM.

RESULTS: Twelve patients with limb-onset ALS (mean age 48.7 years, 75% male) and 13 age-, sex-, and handedness-matched HCs (mean age 44.6 years, 69% male) were included. Compared to HCs, ALS patients demonstrated significantly lower susceptibility in the left caudate nucleus (CN) (SMD = -0.845), right CN (SMD = -0.851), whole CN (SMD = -1.016), and left subthalamic nucleus (STN) (SMD = -1.000). Susceptibility in the left putamen (SMD = -0.857), left thalamus (SMD = -1.081), and whole thalamus (SMD = -0.968) was significantly higher in the patients. The susceptibility of the substantia nigra (SN), CN, and pulvinar was positively correlated with disease duration.

CONCLUSIONS: QSM detects abnormal iron accumulation patterns in the subcortical gray matter of ALS patients, which correlates with disease characteristics, supporting its potential as a neuroimaging biomarker.}, } @article {pmid38956726, year = {2024}, author = {Ye, S and Chen, L and Murphy, D and Wu, J and Zhang, H and Liu, H and Zou, B and Hou, G and Zhang, N and Yin, T and Smith, RA and Fan, D}, title = {Validation of the Center for Neurologic Study Bulbar Function Scale-Chinese version in a population with amyotrophic lateral sclerosis.}, journal = {Orphanet journal of rare diseases}, volume = {19}, number = {1}, pages = {246}, pmid = {38956726}, issn = {1750-1172}, support = {82001350//National Natural Science Foundation of China/ ; 81873784//National Natural Science Foundation of China/ ; 82071426//National Natural Science Foundation of China/ ; YCXJ-JZ-2022-007//Beijing E-Town Cooperation & Development Foundation/ ; YJXJ-JZ-2021-0014//Beijing E-Town Cooperation & Development Foundation/ ; DL2019002//PUTH Cohort Construction Project/ ; }, mesh = {Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; *Amyotrophic Lateral Sclerosis/physiopathology ; }, abstract = {OBJECTIVE: The Center for Neurologic Study Bulbar Function Scale (CNS-BFS) was specifically designed as a self-reported measure of bulbar function. The purpose of this research was to validate the Chinese translation of the CNS-BFSC as an effective measurement for the Chinese population with ALS.

METHODS: A total of 111 ALS patients were included in this study. The CNS-BFSC score, three bulbar function items from the ALSFRS-R, and visual analog scale (VAS) score for speech, swallowing and salivation were assessed in the present study. Forty-six ALS patients were retested on the same scale 5-10 days after the first evaluation.

RESULTS: The CNS-BFSC sialorrhea, speech and swallowing subscores were separately correlated with the VAS subscores (p < 0.001). The CNS-BFSC total score and sialorrhea and speech scores were significantly correlated with the ALSFRS-R bulbar subscore (p < 0.001). The CNS-BFSC total score and ALSFRS-R bulbar subscale score were highly predictive of a clinician diagnosis of impaired bulbar function (area under the receiver operating characteristic curve, 0.947 and 0.911, respectively; p < 0.001). A cutoff value for the CNS-BFSC total score was selected by maximizing Youden's index; this cutoff score was 33, with 86.4% sensitivity and 93.3% specificity. The CNS-BFSC total score and the sialorrhea, speech and swallowing subscores had good-retest reliability (p > 0.05). The Cronbach's α of the CNS-BFSC was 0.972.

CONCLUSION: The Chinese version of the CNS-BFSC has acceptable efficacy and reliability for the assessment of bulbar dysfunction in ALS patients.}, } @article {pmid38956470, year = {2024}, author = {Cai, H and Jiang, H and Xie, D and Lai, Z and Wu, J and Chen, M and Yang, Z and Xu, R and Zeng, S and Ma, H}, title = {Enhancing image quality in computed tomography angiography follow-ups after endovascular aneurysm repair: a comparative study of reconstruction techniques.}, journal = {BMC medical imaging}, volume = {24}, number = {1}, pages = {162}, pmid = {38956470}, issn = {1471-2342}, support = {82202217//National Natural Science Foundation of China/ ; }, mesh = {Humans ; Retrospective Studies ; Female ; *Computed Tomography Angiography/methods ; Aged ; Male ; *Endovascular Procedures/methods ; *Artifacts ; Middle Aged ; Aortic Aneurysm, Abdominal/surgery/diagnostic imaging ; Deep Learning ; Radiographic Image Interpretation, Computer-Assisted/methods ; Stents ; Endovascular Aneurysm Repair ; }, abstract = {BACKGROUND: The image quality of computed tomography angiography (CTA) images following endovascular aneurysm repair (EVAR) is not satisfactory, since artifacts resulting from metallic implants obstruct the clear depiction of stent and isolation lumens, and also adjacent soft tissues. However, current techniques to reduce these artifacts still need further advancements due to higher radiation doses, longer processing times and so on. Thus, the aim of this study is to assess the impact of utilizing Single-Energy Metal Artifact Reduction (SEMAR) alongside a novel deep learning image reconstruction technique, known as the Advanced Intelligent Clear-IQ Engine (AiCE), on image quality of CTA follow-ups conducted after EVAR.

MATERIALS: This retrospective study included 47 patients (mean age ± standard deviation: 68.6 ± 7.8 years; 37 males) who underwent CTA examinations following EVAR. Images were reconstructed using four different methods: hybrid iterative reconstruction (HIR), AiCE, the combination of HIR and SEMAR (HIR + SEMAR), and the combination of AiCE and SEMAR (AiCE + SEMAR). Two radiologists, blinded to the reconstruction techniques, independently evaluated the images. Quantitative assessments included measurements of image noise, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), the longest length of artifacts (AL), and artifact index (AI). These parameters were subsequently compared across different reconstruction methods.

RESULTS: The subjective results indicated that AiCE + SEMAR performed the best in terms of image quality. The mean image noise intensity was significantly lower in the AiCE + SEMAR group (25.35 ± 6.51 HU) than in the HIR (47.77 ± 8.76 HU), AiCE (42.93 ± 10.61 HU), and HIR + SEMAR (30.34 ± 4.87 HU) groups (p < 0.001). Additionally, AiCE + SEMAR exhibited the highest SNRs and CNRs, as well as the lowest AIs and ALs. Importantly, endoleaks and thrombi were most clearly visualized using AiCE + SEMAR.

CONCLUSIONS: In comparison to other reconstruction methods, the combination of AiCE + SEMAR demonstrates superior image quality, thereby enhancing the detection capabilities and diagnostic confidence of potential complications such as early minor endleaks and thrombi following EVAR. This improvement in image quality could lead to more accurate diagnoses and better patient outcomes.}, } @article {pmid38956107, year = {2024}, author = {Opie-Martin, S and Iacoangeli, A and Topp, SD and Abel, O and Mayl, K and Mehta, PR and Shatunov, A and Fogh, I and Bowles, H and Limbachiya, N and Spargo, TP and Al-Khleifat, A and Williams, KL and Jockel-Balsarotti, J and Bali, T and Self, W and Henden, L and Nicholson, GA and Ticozzi, N and McKenna-Yasek, D and Tang, L and Shaw, PJ and Chio, A and Ludolph, A and Weishaupt, JH and Landers, JE and Glass, JD and Mora, JS and Robberecht, W and Damme, PV and McLaughlin, R and Hardiman, O and van den Berg, L and Veldink, JH and Corcia, P and Stevic, Z and Siddique, N and Silani, V and Blair, IP and Fan, DS and Esselin, F and de la Cruz, E and Camu, W and Basak, NA and Siddique, T and Miller, T and Brown, RH and Al-Chalabi, A and Shaw, CE}, title = {Author Correction: The SOD1-mediated ALS phenotype shows a decoupling between age of symptom onset and disease duration.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {5560}, doi = {10.1038/s41467-024-49938-y}, pmid = {38956107}, issn = {2041-1723}, } @article {pmid38955238, year = {2024}, author = {Wang, M and Tang, Z}, title = {No causal relationship between serum urate and neurodegenerative diseases: A Mendelian randomization study.}, journal = {Experimental gerontology}, volume = {194}, number = {}, pages = {112503}, doi = {10.1016/j.exger.2024.112503}, pmid = {38955238}, issn = {1873-6815}, mesh = {Humans ; *Mendelian Randomization Analysis ; *Uric Acid/blood ; *Neurodegenerative Diseases/genetics/blood ; *Amyotrophic Lateral Sclerosis/genetics/blood ; *Genome-Wide Association Study ; Parkinson Disease/genetics/blood ; Multiple Sclerosis/genetics/blood ; Alzheimer Disease/genetics/blood ; Polymorphism, Single Nucleotide ; Causality ; }, abstract = {OBJECTIVE: Observational studies have shown that increased serum urate is associated with a lower risk of neurodegenerative diseases (NDs), but the causality remains unclear. We employed a two-sample Mendelian randomization (MR) approach to assess the causal relationship between serum urate and four common subtypes of NDs, including Parkinson's disease (PD), Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS).

METHODS: Serum urate data came from the CKDGen Consortium. GWAS data for PD, AD, ALS, and MS were obtained from four databases in the primary analysis and then acquired statistics from the FinnGen consortium for replication and meta-analysis. Inverse variance weighted (IVW), weighted median (WM), and MR-Egger regression methods were applied in the MR analyses. Pleiotropic effects, heterogeneity, and leave-one-out analyses were evaluated to validate the results.

RESULTS: There was no evidence for the effect of serum urate on PD (OR: 1.00, 95 % CI: 0.90-1.11, P = 0.97), AD (OR: 1.02, 95 % CI: 1.00-1.04, P = 0.06), ALS (OR: 1.05, 95 % CI: 0.97-1.13, P = 0.22), and MS (OR: 1.01, 95 % CI: 0.89-1.14, P = 0.90) risk when combined with the FinnGen consortium, neither was any evidence of pleiotropy detected between the instrumental variables (IVs).

CONCLUSION: The MR analysis suggested that serum urate may not be causally associated with a risk of PD, AD, ALS, and MS.}, } @article {pmid38954274, year = {2024}, author = {Faltracco, V and Poletti, B and Aiello, EN and Telesca, A and Bella, ED and Bersano, E and Silani, V and Ticozzi, N and Lauria, G and Consonni, M}, title = {Emotional awareness in patients with amyotrophic lateral sclerosis.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {45}, number = {10}, pages = {5043-5046}, pmid = {38954274}, issn = {1590-3478}, support = {2015-0023//Fondazione Regionale per la Ricerca Biomedica, Regione Lombardia/ ; 1157625//Fondo Europeo di Sviluppo Regionale, Regione Lombardia (POR FESR 2014-2020)/ ; RRC//Ministero della Salute/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/psychology/complications ; Male ; Female ; *Affective Symptoms/etiology/physiopathology ; Middle Aged ; Aged ; Emotions/physiology ; Awareness/physiology ; Neuropsychological Tests ; Cohort Studies ; }, abstract = {INTRODUCTION: It has been recently acknowledged that deficits in experiencing and processing one's own emotions, also termed alexithymia, may possibly feature the frontotemporal-spectrum disorders. This study aims to determine whether alexithymia could be included within the frontotemporal syndromes of amyotrophic lateral sclerosis (ALS).

METHODS: Alexithymic traits were estimated in a cohort of 68 non-demented ALS patients with the 20-item Toronto Alexithymia Scale (TAS-20). Patients were assessed for the identification of motor-phenotypes and frontotemporal syndromes based on current classification criteria. Spearman's coefficients explored the correlates of TAS-20 measures with motor-functional profiles, global cognitive, social-cognitive (emotion recognition and empathy) and behavioral status.

RESULTS: Abnormal TAS-20 scores were found in 13% of patients, and their distribution did not vary within motor and frontotemporal phenotypes. Significant associations were detected between TAS-20 and executive (p ≤ .011), memory (p = .006), state-anxiety (p ≤ .013) and depression measures (p ≤ .010). By contrast, TAS-20 scores were unrelated to social-cognitive performances, dysexecutive and apathetic profiles. Disease duration was the only motor-functional feature being related to the TAS-20 (p ≤ .008).

CONCLUSIONS: Alexithymia of potential clinical relevance occur in a minority of ALS patients, and its neuropsychological correlates mostly resemble those featuring the general population. Hence, it is unlikely that alexithymia is a specific feature of frontotemporal-spectrum characterizing ALS, rather it could be an expression of psychogenic factors as a reaction to the disease.}, } @article {pmid38954254, year = {2025}, author = {Wang, Y and Wang, Y and Yin, H and Xiao, Z and Ren, Z and Ma, X and Zhang, J and Fu, X and Zhang, F and Zeng, L}, title = {BI1 Activates Autophagy and Mediates TDP43 to Regulate ALS Pathogenesis.}, journal = {Molecular neurobiology}, volume = {62}, number = {1}, pages = {988-1030}, pmid = {38954254}, issn = {1559-1182}, mesh = {*Amyotrophic Lateral Sclerosis/metabolism/pathology/genetics ; *Autophagy/physiology ; Animals ; *DNA-Binding Proteins/metabolism/genetics ; *Motor Neurons/metabolism/pathology ; *Mice, Transgenic ; Humans ; Mitochondria/metabolism ; Apoptosis Regulatory Proteins/metabolism ; Apoptosis ; Mice ; Neuromuscular Junction/metabolism/pathology ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is the most prevalent motor neuron disease in adults. Currently, there are no known drugs or clinical approaches that have demonstrated efficacy in treating ALS. Mitochondrial function and autophagy have been identified as crucial mechanisms in the development of ALS. While Bax inhibitor 1 (BI1) has been implicated in neurodegenerative diseases, its exact mechanism remains unknown. This study investigates the therapeutic impact of BI1 overexpression on ALS both in vivo and in vitro, revealing its ability to mitigate SOD1[G93A]-induced apoptosis, nuclear damage, mitochondrial dysfunction, and axonal degeneration of motor neurons. At the same time, BI1 prolongs onset time and lifespan of ALS mice, improves motor function, and alleviates neuronal damage, muscle damage, neuromuscular junction damage among other aspects. The findings indicate that BI1 can inhibit pathological TDP43 morphology and initially stimulate autophagy through interaction with TDP43. This study establishes a solid theoretical foundation for understanding the regulation of autophagy by BI1 and TDP43 while shedding light on the pathogenesis of ALS through their interaction - offering new concepts and targets for clinical implementation and drug development.}, } @article {pmid38953009, year = {2024}, author = {Rostás, R and Fekete, I and Horváth, L and Márton, S and Fekete, K}, title = {Correlation of single-fiber electromyography studies and functional status in patients with amyotrophic lateral sclerosis.}, journal = {Open medicine (Warsaw, Poland)}, volume = {19}, number = {1}, pages = {20240990}, pmid = {38953009}, issn = {2391-5463}, abstract = {OBJECTIVE: Our aim was to examine the significance of single-fiber electromyography (SFEMG) in patients diagnosed with amyotrophic lateral sclerosis (ALS) and determine the best correlating parameter with SFEMG parameters and clinical scales across different muscles including facial muscles.

METHODS: SFEMG examinations were conducted on the extensor digitorum (ED), frontalis, and orbicularis oculi muscles. Mean jitter, percentage of increased jitter, fiber density (FD), and impulse blocking percentage were compared to reference values and functional scales.

RESULTS: Significant differences (p < 0.001) were observed between the patients' SFEMG results and reference values in all muscles. Significant correlations were found between SFEMG parameters and clinical scales, particularly when considering both FD and jitter. A notable value of the ALS Functional Rating Scale Revised (ALSFRS-R) was detected in all muscles: 31 points in the ED muscle, 30 in the orbicularis oculi muscle, and 31 in the frontalis muscle. Below this ALSFRS-R threshold, the percentage of increased jitter was higher, while FD remained relatively low.

CONCLUSION: SFEMG examination emerges as a valuable tool for better understanding ALS and holds potential for assessing prognosis. Combined jitter and FD analysis showed the strongest correlation with clinical scales. In addition to the ED muscle, the orbicularis oculi muscle may be important in the assessment.}, } @article {pmid38951798, year = {2024}, author = {Pottinger, TD and Motelow, JE and Povysil, G and Moreno, CAM and Ren, Z and Phatnani, H and , and Aitman, TJ and Santoyo-Lopez, J and , and Mitsumoto, H and , and , and , and Goldstein, DB and Harms, MB}, title = {Rare variant analyses validate known ALS genes in a multi-ethnic population and identifies ANTXR2 as a candidate in PLS.}, journal = {BMC genomics}, volume = {25}, number = {1}, pages = {651}, pmid = {38951798}, issn = {1471-2164}, support = {P01 AG007232/AG/NIA NIH HHS/United States ; U19 AI067854/AI/NIAID NIH HHS/United States ; R01 AG037212/AG/NIA NIH HHS/United States ; UM1 AI100645/AI/NIAID NIH HHS/United States ; T32 HL144442/HL/NHLBI NIH HHS/United States ; }, mesh = {Female ; Humans ; Male ; *Amyotrophic Lateral Sclerosis/genetics ; Ethnicity/genetics ; Genetic Predisposition to Disease ; Genetic Variation ; European People ; East Asian People ; African People ; Hispanic or Latino ; Middle Eastern People ; South Asian People ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease affecting over 300,000 people worldwide. It is characterized by the progressive decline of the nervous system that leads to the weakening of muscles which impacts physical function. Approximately, 15% of individuals diagnosed with ALS have a known genetic variant that contributes to their disease. As therapies that slow or prevent symptoms continue to develop, such as antisense oligonucleotides, it is important to discover novel genes that could be targets for treatment. Additionally, as cohorts continue to grow, performing analyses in ALS subtypes, such as primary lateral sclerosis (PLS), becomes possible due to an increase in power. These analyses could highlight novel pathways in disease manifestation.

METHODS: Building on our previous discoveries using rare variant association analyses, we conducted rare variant burden testing on a substantially larger multi-ethnic cohort of 6,970 ALS patients, 166 PLS patients, and 22,524 controls. We used intolerant domain percentiles based on sub-region Residual Variation Intolerance Score (subRVIS) that have been described previously in conjunction with gene based collapsing approaches to conduct burden testing to identify genes that associate with ALS and PLS.

RESULTS: A gene based collapsing model showed significant associations with SOD1, TARDBP, and TBK1 (OR = 19.18, p = 3.67 × 10[-39]; OR = 4.73, p = 2 × 10[-10]; OR = 2.3, p = 7.49 × 10[-9], respectively). These genes have been previously associated with ALS. Additionally, a significant novel control enriched gene, ALKBH3 (p = 4.88 × 10[-7]), was protective for ALS in this model. An intolerant domain-based collapsing model showed a significant improvement in identifying regions in TARDBP that associated with ALS (OR = 10.08, p = 3.62 × 10[-16]). Our PLS protein truncating variant collapsing analysis demonstrated significant case enrichment in ANTXR2 (p = 8.38 × 10[-6]).

CONCLUSIONS: In a large multi-ethnic cohort of 6,970 ALS patients, collapsing analyses validated known ALS genes and identified a novel potentially protective gene, ALKBH3. A first-ever analysis in 166 patients with PLS found a candidate association with loss-of-function mutations in ANTXR2.}, } @article {pmid38951432, year = {2024}, author = {Didcote, L and Vitoratou, S and Al-Chalabi, A and Goldstein, LH}, title = {Comparison of in-person vs. remote administration of cognitive screening tools for people with ALS.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {45}, number = {11}, pages = {5309-5317}, pmid = {38951432}, issn = {1590-3478}, support = {MR/R024804/1/MRC_/Medical Research Council/United Kingdom ; Goldstein/Oct17/892-792/MNDA_/Motor Neurone Disease Association/United Kingdom ; }, mesh = {Humans ; Male ; Female ; *Amyotrophic Lateral Sclerosis/diagnosis/psychology ; Middle Aged ; Aged ; *Neuropsychological Tests ; Videoconferencing ; Cognition Disorders/diagnosis/etiology ; Cognitive Dysfunction/diagnosis/etiology ; }, abstract = {OBJECTIVE: This study investigated whether cognitive screening tools used for people with amyotrophic lateral sclerosis (pwALS) are affected by the screen being administered face-to-face or remotely online. It also investigated whether demographic variables predicted total cognitive screen scores.

METHODS: The cognitive component of the Edinburgh Cognitive and Behavioural ALS Screen (ECASc), the cognitive component of the ALS Cognitive Behavioural Screen (ALS-CBSc), and the Mini Addenbrooke's Cognitive Examination (Mini-ACE) were administered to 41 pwALS and 41 controls face-to-face. Versions of the cognitive screens designed to be administered remotely were administered to 57 pwALS and 44 controls via videoconferencing methods. Backwards stepwise linear regressions were conducted to assess whether total scores on the ECASc, ALS-CBSc, and Mini-ACE scores were predicted by administration mode (face-to-face or remote) or demographic variables.

RESULTS: Mode of administration significantly affected scores on the ECASc and ALS-CBSc; remote administration was associated with better total scores. Administration mode did not significantly affect Mini-ACE scores. All cognitive screens were significantly affected by IQ scores; higher IQ scores predicted better screening tool scores. Only ECASc scores were significantly affected by age, with older age predicting poorer scores. Being female was associated with better Mini-ACE scores; sex did not predict ECASc and ALS-CBSc scores.

CONCLUSIONS: Our results suggest that videoconferencing versions of the ECASc and ALS-CBSc may function differently to the original, face-to-face versions. There are advantages to using remote versions of cognitive screening tools but clinicians and researchers who use them should consider that they may not yield equivalent scores.}, } @article {pmid38951089, year = {2024}, author = {Zhang, JH and Chen, ZH and Ling, L and Cheng, HM and Zhang, Y and Zhao, JR and Huang, XS}, title = {[Analysis of the characteristics of patients with amyotrophic lateral sclerosis with neuromuscular junction dysfunction prior to motor neuron degeneration].}, journal = {Zhonghua nei ke za zhi}, volume = {63}, number = {7}, pages = {660-665}, doi = {10.3760/cma.j.cn112138-20230811-00049}, pmid = {38951089}, issn = {0578-1426}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology ; *Electromyography ; *Motor Neurons/physiology ; Neuromuscular Junction/physiopathology ; Electric Stimulation ; Accessory Nerve/physiopathology ; Male ; Female ; Middle Aged ; }, abstract = {Objective: To investigate the clinical and electrophysiological characteristics of patients with amyotrophic lateral sclerosis (ALS) with positive repetitive nerve stimulation (RNS) test results on the accessory nerve and negative needle electromyography (EMG) test results on the sternocleidomastoid with the goal to enrich the knowledge of disease progression in patients with ALS. Methods: The clinical data of 612 patients diagnosed with ALS at the Neurology Department of the First Medical Center, Chinese PLA General Hospital from June 2016 to August 2022 were collected. In total, 267 cases had undergone EMG tests on the sternocleidomastoid following a positive 3 Hz RNS test result on the accessory nerve, who were selected as the study subjects. The differences in clinical indicators were compared between RNS (+)/EMG (-) group and RNS (+)/EMG (+) group. A binomial distribution model with multiple variables was built to quantitatively analyze the major factors and their effects. Results: At the initial visit, 15.8% of patients with ALS were 3 Hz RNS (+) on the accessory nerve and EMG (-) on the ipsilateral sternocleidomastoid, accounting for 36.3% of RNS (+) patients. The decremental range of the 3 Hz RNS test delivered to the accessory nerve in these patients [-14% (-19%, -12%)] was lower than that in patients with RNS (+)/EMG (+) [-17% (-23%, -13%)] (P<0.05), while the ratio of upper limb onset (64.9%) and non-definite diagnosis (28.9%) were higher [54.7% and 13.5% for patients with RNS (+)/EMG (+), P<0.05]. Furthermore, the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) score [40 (37, 42)], body mass index (BMI) [23.8 (22.0, 25.4) kg/m[2]] and forced vital capacity (FVC) [92.8% (76.6%, 103.8%)] were higher in patients with RNS(+)/EMG(+) (P<0.05). The multivariate model suggested that, in patients with RNS (+)/EMG (-), the ratio of upper limb onset to lower limb onset was 1.04, while that of upper limb onset to bulbar onset was 2.02, and that of lower limb onset to bulbar onset was 1.94. The ratio of non-definite ALS to definite ALS was 1.13. The ALSFRS-R score, BMI, and FVC had a protective contribution to the electrophysiological function of the motor neurons. The ratio of the effect size of the ALSFRS-R or BMI to that of FVC was 3.37 and 1.14, respectively. Conclusions: Patients with ALS that were 3 Hz RNS (+) on the accessory nerve and EMG (-) on the ipsilateral sternocleidomastoid had a smaller decremental range of the compound muscle action potential amplitude, and a higher proportion of upper limb onset and non-definite ALS. A higher ALSFRS-R score, BMI, and FVC have a protective effect to the electrophysiological function of motor neurons. The effect size of the ALSFRS-R score is the largest, followed by BMI and FVC.}, } @article {pmid38948094, year = {2024}, author = {Haider, KH}, title = {Priming mesenchymal stem cells to develop "super stem cells".}, journal = {World journal of stem cells}, volume = {16}, number = {6}, pages = {623-640}, pmid = {38948094}, issn = {1948-0210}, abstract = {The stem cell pre-treatment approaches at cellular and sub-cellular levels encompass physical manipulation of stem cells to growth factor treatment, genetic manipulation, and chemical and pharmacological treatment, each strategy having advantages and limitations. Most of these pre-treatment protocols are non-combinative. This editorial is a continuum of Li et al's published article and Wan et al's editorial focusing on the significance of pre-treatment strategies to enhance their stemness, immunoregulatory, and immunosuppressive properties. They have elaborated on the intricacies of the combinative pre-treatment protocol using pro-inflammatory cytokines and hypoxia. Applying a well-defined multi-pronged combinatorial strategy of mesenchymal stem cells (MSCs), pre-treatment based on the mechanistic understanding is expected to develop "Super MSCs", which will create a transformative shift in MSC-based therapies in clinical settings, potentially revolutionizing the field. Once optimized, the standardized protocols may be used with slight modifications to pre-treat different stem cells to develop "super stem cells" with augmented stemness, functionality, and reparability for diverse clinical applications with better outcomes.}, } @article {pmid38946834, year = {2024}, author = {Taherifard, E and Saeed, A}, title = {Predicting liver function after hemihepatectomy in patients with hepatocellular carcinoma using different modalities.}, journal = {World journal of clinical oncology}, volume = {15}, number = {6}, pages = {783-785}, pmid = {38946834}, issn = {2218-4333}, abstract = {In response to Dr. Yue et al's study on prognostic factors for post-hemihepatectomy outcomes in hepatocellular carcinoma (HCC) patients, this critical review identifies methodological limitations and proposes enhancements for future research. While the study identifies liver stiffness measure and standard residual liver volume as potential predictors, concerns regarding small sample size, reliance on biochemical markers for safety assessment, and inadequate adjustment for confounding variables are raised. Recommendations for rigorous methodology, including robust statistical analysis, consideration of confounding factors, and selection of outcome measures with clinical components, are proposed to strengthen prognostic assessments. Furthermore, validation of novel evaluation models is crucial for enhancing clinical applicability and advancing understanding of postoperative outcomes in patients with HCC undergoing hemihepatectomy.}, } @article {pmid38946579, year = {2024}, author = {Trucco, AP and Backhouse, T and Mioshi, E}, title = {Describing and assessing behavioural symptoms in amyotrophic lateral sclerosis with and without frontotemporal dementia: a scoping review.}, journal = {Current opinion in neurology}, volume = {37}, number = {5}, pages = {603-610}, pmid = {38946579}, issn = {1473-6551}, mesh = {Humans ; *Frontotemporal Dementia/psychology/physiopathology/diagnosis ; *Amyotrophic Lateral Sclerosis/psychology/complications/diagnosis ; Behavioral Symptoms/etiology/diagnosis ; }, abstract = {PURPOSE OF REVIEW: Alongside motor and cognitive symptoms, amyotrophic lateral sclerosis (ALS) and ALS with frontotemporal dementia (ALSFTD) present with behavioural symptoms, which can be challenging for all affected by the disease. A scoping review of studies published between 2011 and 2024 was conducted to present the breadth of behavioural symptoms in ALS and ALSFTD, explore how they are described and assessed, and identify patterns in the literature.

FINDINGS: This scoping review identified 3939 articles, with 111/3939 meeting eligibility criteria. Most studies were from Australia (23.22%), Italy (16.94%) and the UK (14.29%); 75.67% were cross-sectional. Sample size ranged from 1 to 1013, as case studies were included. Overall mean age (100/111 studies) was 61.32 (SD = 4.15). Proportion of male patients (reported 102/111 studies) was 61.49%; mean disease duration (reported in 86/111 records) was 32.63 months (SD = 24.72). Papers described a broad range of behavioural symptoms (465 examples), which were thematically collated into seven categories: disinhibition (27.74%), apathy (25.16%), perseverative/compulsive behaviours (17.42%), hyperorality (10.53%), loss of sympathy or empathy (8.6%), psychotic symptoms (7.74%), and loss of insight about disease and changes (2.8%). Most studies (78.37%) used validated behavioural assessments that elicited carer's perspectives.

SUMMARY: Despite extensive evidence of behavioural symptoms in ALS, implementation of assessments and management of behavioural symptoms in clinical care remain limited. Clinicians must assess behavioural symptoms, as these can negatively affect disease prognosis, patient treatment engagement and increase family distress. Measures capturing carers' perspectives through interviews are ideal as they can reveal anosognosia, lack of sympathy and lack of empathy.}, } @article {pmid38944367, year = {2024}, author = {Wankhede, NL and Rajendra Kopalli, S and Dhokne, MD and Badnag, DJ and Chandurkar, PA and Mangrulkar, SV and Shende, PV and Taksande, BG and Upaganlawar, AB and Umekar, MJ and Koppula, S and Kale, MB}, title = {Decoding mitochondrial quality control mechanisms: Identifying treatment targets for enhanced cellular health.}, journal = {Mitochondrion}, volume = {78}, number = {}, pages = {101926}, doi = {10.1016/j.mito.2024.101926}, pmid = {38944367}, issn = {1872-8278}, mesh = {Humans ; *Mitochondria/metabolism ; *Neurodegenerative Diseases/metabolism/therapy ; Animals ; }, abstract = {Mitochondria are singular cell organelles essential for many cellular functions, which includes responding to stress, regulating calcium levels, maintaining protein homeostasis, and coordinating apoptosis response. The vitality of cells, therefore, hinges on the optimal functioning of these dynamic organelles. Mitochondrial Quality Control Mechanisms (MQCM) play a pivotal role in ensuring the integrity and functionality of mitochondria. Perturbations in these mechanisms have been closely associated with the pathogenesis of neurodegenerative disorders such as Parkinson's disease, Alzheimer's disease, Huntington's disease, and amyotrophic lateral sclerosis. Compelling evidence suggests that targeting specific pathways within the MQCM could potentially offer a therapeutic avenue for rescuing mitochondrial integrity and mitigating the progression of neurodegenerative diseases. The intricate interplay of cellular stress, protein misfolding, and impaired quality control mechanisms provides a nuanced understanding of the underlying pathology. Consequently, unravelling the specific MQCM dysregulation in neurodegenerative disorders becomes paramount for developing targeted therapeutic strategies. This review delves into the impaired MQCM pathways implicated in neurodegenerative disorders and explores emerging therapeutic interventions. By shedding light on pharmaceutical and genetic manipulations aimed at restoring MQCM efficiency, the discussion aims to provide insights into novel strategies for ameliorating the progression of neurodegenerative diseases. Understanding and addressing mitochondrial quality control mechanisms not only underscore their significance in cellular health but also offer a promising frontier for advancing therapeutic approaches in the realm of neurodegenerative disorders.}, } @article {pmid38943180, year = {2024}, author = {Wiesner, D and Feldengut, S and Woelfle, S and Boeckers, TM and Ludolph, AC and Roselli, F and Del Tredici, K}, title = {Neuropeptide FF (NPFF)-positive nerve cells of the human cerebral cortex and white matter in controls, selected neurodegenerative diseases, and schizophrenia.}, journal = {Acta neuropathologica communications}, volume = {12}, number = {1}, pages = {108}, pmid = {38943180}, issn = {2051-5960}, support = {446067541//Deutsche Forschungsgemeinschaft/ ; 443642953//Deutsche Forschungsgemeinschaft/ ; 431995586//Deutsche Forschungsgemeinschaft/ ; 251293561//Deutsche Forschungsgemeinschaft/ ; }, mesh = {Humans ; *White Matter/pathology/metabolism ; Male ; *Schizophrenia/pathology/metabolism ; Female ; *Cerebral Cortex/pathology/metabolism ; Aged ; Middle Aged ; *Neurodegenerative Diseases/pathology/metabolism ; Aged, 80 and over ; Oligopeptides ; Adult ; Neurons/pathology/metabolism ; }, abstract = {We quantified and determined for the first time the distribution pattern of the neuropeptide NPFF in the human cerebral cortex and subjacent white matter. To do so, we studied n = 9 cases without neurological disorders and n = 22 cases with neurodegenerative diseases, including sporadic amyotrophic lateral sclerosis (ALS, n = 8), Alzheimer's disease (AD, n = 8), Pick's disease (PiD, n = 3), and schizophrenia (n = 3). NPFF-immunopositive cells were located chiefly, but not exclusively, in the superficial white matter and constituted there a subpopulation of white matter interstitial cells (WMIC): Pyramidal-like and multipolar somata predominated in the gyral crowns, whereas bipolar and ovoid somata predominated in the cortex surrounding the sulci. Their sparsely ramified axons were unmyelinated and exhibited NPFF-positive bead-like varicosities. We found significantly fewer NPFF-immunopositive cells in the gray matter of the frontal, cingulate, and superior temporal gyri of both sporadic ALS and late-stage AD patients than in controls, and significantly fewer NPFF-positive cells in the subjacent as well as deep white matter of the frontal gyrus of these patients compared to controls. Notably, the number of NPFF-positive cells was also significantly lower in the hippocampal formation in AD compared to controls. In PiD, NPFF-positive cells were present in significantly lower numbers in the gray and white matter of the cingulate and frontal gyrii in comparison to controls. In schizophrenic patients, lower wNPFF cell counts in the neocortex were significant and global (cingulate, frontal, superior temporal gyrus, medial, and inferior gyri). The precise functions of NPFF-positive cells and their relationship to the superficial corticocortical white matter U-fibers are currently unknown. Here, NPFF immunohistochemistry and expression characterize a previously unrecognized population of cells in the human brain, thereby providing a new entry-point for investigating their physiological and pathophysiological roles.}, } @article {pmid38943019, year = {2024}, author = {He, S and He, XX and Yang, HQ and Zhang, JW and Chen, S}, title = {Two new cases with the UBQLN2 gene mutation in Han Chinese.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {45}, number = {10}, pages = {5047-5051}, pmid = {38943019}, issn = {1590-3478}, mesh = {Humans ; Female ; Male ; *Autophagy-Related Proteins/genetics ; Middle Aged ; *Mutation ; Young Adult ; Amyotrophic Lateral Sclerosis/genetics ; Adaptor Proteins, Signal Transducing/genetics ; China ; Adult ; Pedigree ; East Asian People ; }, abstract = {Variations in the UBQLN2 gene are associated with a group of diseases with X-linked dominant inheritance and clinical phenotypes of amyotrophic lateral sclerosis (ALS) and/or frontal temporal lobe dementia (FTD). Cases with UBQLN2 variations have been rarely reported worldwide. The reported cases exhibit strong clinical heterogeneity. Here, we report two adult-onset cases with UBQLN2 variations in Han Chinese. Whole exome sequencing revealed the hemizygous P506S (c.1516C > T) and the heterozygous P509S variation (c.1525C > T), both of which were located within the hotspot mutation region. The patient with the P506S variation was a 24-year-old male. The clinical feature was spastic paraplegia without lower motor neuron damage. The patient's mother was an asymptomatic heterozygote carrier with skewed X-chromosome inactivation. The patient with the P509S variation was a 63-year-old female. Clinical features included ALS and parkinsonism. [18]F-fluorodopa PET-CT revealed presynaptic dopaminergic deficits in bilateral posterior putamen. These cases further highlight the clinical heterogeneity of UBQLN2 cases.}, } @article {pmid38942541, year = {2024}, author = {Shukla, H and John, D and Banerjee, S and Tiwari, AK}, title = {Drug repurposing for neurodegenerative diseases.}, journal = {Progress in molecular biology and translational science}, volume = {207}, number = {}, pages = {249-319}, doi = {10.1016/bs.pmbts.2024.03.035}, pmid = {38942541}, issn = {1878-0814}, mesh = {Humans ; *Drug Repositioning ; *Neurodegenerative Diseases/drug therapy ; Animals ; }, abstract = {Neurodegenerative diseases (NDDs) are neuronal problems that include the brain and spinal cord and result in loss of sensory and motor dysfunction. Common NDDs include Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), Multiple Sclerosis (MS), and Amyotrophic Lateral Sclerosis (ALS) etc. The occurrence of these diseases increases with age and is one of the challenging problems among elderly people. Though, several scientific research has demonstrated the key pathologies associated with NDDs still the underlying mechanisms and molecular details are not well understood and need to be explored and this poses a lack of effective treatments for NDDs. Several lines of evidence have shown that NDDs have a high prevalence and affect more than a billion individuals globally but still, researchers need to work forward in identifying the best therapeutic target for NDDs. Thus, several researchers are working in the directions to find potential therapeutic targets to alter the disease pathology and treat the diseases. Several steps have been taken to identify the early detection of the disease and drug repurposing for effective treatment of NDDs. Moreover, it is logical that current medications are being evaluated for their efficacy in treating such disorders; therefore, drug repurposing would be an efficient, safe, and cost-effective way in finding out better medication. In the current manuscript we discussed the utilization of drugs that have been repurposed for the treatment of AD, PD, HD, MS, and ALS.}, } @article {pmid38941189, year = {2024}, author = {Huang, WP and Ellis, BCS and Hodgson, RE and Sanchez Avila, A and Kumar, V and Rayment, J and Moll, T and Shelkovnikova, TA}, title = {Stress-induced TDP-43 nuclear condensation causes splicing loss of function and STMN2 depletion.}, journal = {Cell reports}, volume = {43}, number = {7}, pages = {114421}, doi = {10.1016/j.celrep.2024.114421}, pmid = {38941189}, issn = {2211-1247}, support = {MR/W028522/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Humans ; *DNA-Binding Proteins/metabolism/genetics ; *RNA Splicing/genetics ; *Cell Nucleus/metabolism ; *Amyotrophic Lateral Sclerosis/metabolism/genetics/pathology ; Stress, Physiological ; Animals ; Mice ; }, abstract = {TDP-43 protein is dysregulated in several neurodegenerative diseases, which often have a multifactorial nature and may have extrinsic stressors as a "second hit." TDP-43 undergoes reversible nuclear condensation in stressed cells including neurons. Here, we demonstrate that stress-inducible nuclear TDP-43 condensates are RNA-depleted, non-liquid assemblies distinct from the known nuclear bodies. Their formation requires TDP-43 oligomerization and ATP and is inhibited by RNA. Using a confocal nanoscanning assay, we find that amyotrophic lateral sclerosis (ALS)-linked mutations alter stress-induced TDP-43 condensation by changing its affinity to liquid-like ribonucleoprotein assemblies. Stress-induced nuclear condensation transiently inactivates TDP-43, leading to loss of interaction with its protein binding partners and loss of function in splicing. Splicing changes are especially prominent and persisting for STMN2 RNA, and STMN2 protein becomes rapidly depleted early during stress. Our results point to early pathological changes to TDP-43 in the nucleus and support therapeutic modulation of stress response in ALS.}, } @article {pmid38940407, year = {2024}, author = {Xu, A and Liu, T and Liu, D and Li, W and Huang, H and Wang, S and Xu, L and Liu, X and Jiang, S and Chen, Y and Sun, M and Luo, Q and Ding, T and Yao, T}, title = {Edge-Rich Pt-O-Ce Sites in CeO2 Supported Patchy Atomic-Layer Pt Enable a Non-CO Pathway for Efficient Methanol Oxidation.}, journal = {Angewandte Chemie (International ed. in English)}, volume = {63}, number = {40}, pages = {e202410545}, doi = {10.1002/anie.202410545}, pmid = {38940407}, issn = {1521-3773}, support = {12025505//the National Natural Science Foundation of China/ ; 22179125//the National Natural Science Foundation of China/ ; 12205304//the National Natural Science Foundation of China/ ; KY9990000214//USTC research startup funds/ ; 2021YFA1600800//the National Key R&D Program of China/ ; XDB0450200//the Strategic Priority Research Program of the Chinese Academy of Sciences/ ; GXXT-2020-053//the University of China Innovation Program of Anhui Province/ ; 2022458//the Youth Innovation Promotion Association CAS/ ; 2021TQ0319//the Fellowship of China Postdoctoral Science Foundation/ ; BX20240350//the Fellowship of China Postdoctoral Science Foundation/ ; WK2060000038//the Fundamental Research Funds for the Central Universities/ ; WK2310000113//the Fundamental Research Funds for the Central Universities/ ; }, abstract = {Rational design of efficient methanol oxidation reaction (MOR) catalyst that undergo non-CO pathway is essential to resolve the long-standing poisoning issue. However, it remains a huge challenge due to the rather difficulty in maximizing the non-CO pathway by the selective coupling between the key *CHO and *OH intermediates. Here, we report a high-performance electrocatalyst of patchy atomic-layer Pt epitaxial growth on CeO2 nanocube (Pt ALs/CeO2) with maximum electronic metal-support interaction for enhancing the coupling selectively. The small-size monolayer material achieves an optimal geometrical distance between edge Pt-O-Ce sites and *OH absorbed on CeO2, which well restrains the dehydrogenation of *CHO, resulting in the non-CO pathway. Meanwhile, the *CHO/*CO intermediate generated at inner Pt-O-Ce sites can migrate to edge, inducing the subsequent coupling reaction, thus avoiding poisoning while promoting reaction efficiency. Consequently, Pt ALs/CeO2 exhibits exceptionally catalytic stability with negligible degradation even under 1000 s pure CO poisoning operation and high mass activity (14.87 A/mgPt), enabling it one of the best-performing alkali-stable MOR catalysts.}, } @article {pmid38939990, year = {2024}, author = {Song, XY and Fan, CX and Rahman, AU and Choudhary, MI and Wang, XP}, title = {Neuro-regeneration or Repair: Cell Therapy of Neurological Disorders as A Way Forward.}, journal = {Current neuropharmacology}, volume = {22}, number = {14}, pages = {2272-2283}, pmid = {38939990}, issn = {1875-6190}, mesh = {Humans ; *Nervous System Diseases/therapy ; Animals ; *Cell- and Tissue-Based Therapy/methods ; Nerve Regeneration/physiology ; Stem Cell Transplantation/methods ; }, abstract = {The human central nervous system (CNS) has a limited capacity for regeneration and repair, as many other organs do. Partly as a result, neurological diseases are the leading cause of medical burden globally. Most neurological disorders cannot be cured, and primary treatments focus on managing their symptoms and slowing down their progression. Cell therapy for neurological disorders offers several therapeutic potentials and provides hope for many patients. Here we provide a general overview of cell therapy in neurological disorders such as Parkinson's disease (PD), Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), Wilson's disease (WD), stroke and traumatic brain injury (TBI), involving many forms of stem cells, including embryonic stem cells and induced pluripotent stem cells. We also address the current concerns and perspectives for the future. Most studies for cell therapy in neurological diseases are in the pre-clinical stage, and there is still a great need for further research to translate neural replacement and regenerative therapies into clinical settings.}, } @article {pmid38939546, year = {2024}, author = {Kararia, N and Kararia, V and Sharma, D and Gupta, S and Chaturvedi, S and Chaturvedi, Y}, title = {Comparative evaluation of the accuracy of two electronic apex locators in detecting simulated incomplete vertical root fractures: An in vitro stereomicroscopic study.}, journal = {Journal of conservative dentistry and endodontics}, volume = {27}, number = {5}, pages = {540-544}, pmid = {38939546}, issn = {2950-4708}, abstract = {AIM: The aim of this study was to compare the accuracy of two different electronic apex locators (EALs) in detecting simulated incomplete vertical root fractures (VRFs).

MATERIALS AND METHODS: Thirty freshly extracted single-rooted teeth were randomly divided into three groups of 10 teeth each labeled as Groups A, B, and C. Incomplete VRFs were simulated in the coronal, middle, and apical one-third of the roots for Groups A, B, and C, respectively. The teeth were embedded in alginate mold and fracture location was determined with Root ZX and Propex EALs for each sample and each group. To calculate the actual length (AL), each sample was sectioned at the upper level of the vertical fracture, and the length was measured by setting the stopper of the #10 K file under a stereomicroscope at ×30 magnification. The electronic lengths and ALs were compared using computer software, and the results were analyzed using SPSS 28.0 at a 95% confidence level.

RESULTS: No significant differences were seen in the accuracy of the two EALs when compared with ALs. Root ZX showed significantly longer measurements than ALs in groups B and C.

CONCLUSION: The tested EALs showed low accuracy (20%) in detecting simulated incomplete VRFs with a tendency for longer measurements compared to ALs.}, } @article {pmid38937912, year = {2024}, author = {Verde, F and Licaj, S and Soranna, D and Ticozzi, N and Silani, V and Zambon, A}, title = {Cerebrospinal fluid and blood neurofilament light chain levels in amyotrophic lateral sclerosis and frontotemporal degeneration: A meta-analysis.}, journal = {European journal of neurology}, volume = {31}, number = {9}, pages = {e16371}, pmid = {38937912}, issn = {1468-1331}, support = {//Ministero della Salute/ ; //BIBLIOSAN/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/cerebrospinal fluid/blood ; Humans ; *Neurofilament Proteins/blood/cerebrospinal fluid ; *Frontotemporal Lobar Degeneration/blood/cerebrospinal fluid ; Biomarkers/cerebrospinal fluid/blood ; Frontotemporal Dementia/cerebrospinal fluid/blood ; }, abstract = {BACKGROUND AND PURPOSE: Neurofilament light chain (NFL) has been shown to be increased in amyotrophic lateral sclerosis (ALS) and, to a lesser extent, in frontotemporal dementia (FTD). A meta-analysis of NFL in ALS and FTD was performed.

METHODS: Available studies comparing cerebrospinal fluid and blood NFL levels in ALS versus neurologically healthy controls (NHCs), other neurological diseases (ONDs) and ALS mimics, as well as in FTD and related entities (behavioural variant of FTD and frontotemporal lobar degeneration syndromes) versus NHCs, ONDs and other dementias were evaluated.

RESULTS: In ALS, both cerebrospinal fluid and blood levels of NFL were higher compared to other categories. In FTD, behavioural variant of FTD and frontotemporal lobar degeneration syndromes, NFL levels were consistently higher compared to NHCs; however, several comparisons with ONDs and other dementias did not demonstrate significant differences.

DISCUSSION: Amyotrophic lateral sclerosis is characterized by higher NFL levels compared to most other conditions. In contrast, NFL is not as good at discriminating FTD from other dementias.}, } @article {pmid38936435, year = {2024}, author = {Tondo, G and Mazzini, L and Caminiti, SP and Gallo, C and Matheoud, R and Comi, C and Sacchetti, GM and Perani, D and De Marchi, F}, title = {Coupling motor evoked potentials and brain [[18]F]FDG-PET in Amyotrophic Lateral Sclerosis: preliminary findings on disease severity.}, journal = {Neurobiology of disease}, volume = {199}, number = {}, pages = {106579}, doi = {10.1016/j.nbd.2024.106579}, pmid = {38936435}, issn = {1095-953X}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnostic imaging/metabolism/physiopathology ; Male ; Female ; Middle Aged ; *Fluorodeoxyglucose F18 ; *Positron-Emission Tomography/methods ; *Transcranial Magnetic Stimulation/methods ; Aged ; Retrospective Studies ; *Brain/diagnostic imaging/metabolism/physiopathology ; *Evoked Potentials, Motor/physiology ; Adult ; Severity of Illness Index ; }, abstract = {BACKGROUND: The diagnosis of amyotrophic lateral sclerosis (ALS) is primarily clinical, supported by the electromyographic examination to reveal signs of lower motor neuron damage. Identifying reliable markers of upper motor neuron (UMN) involvement is challenging. On this regard, the role of transcranial magnetic stimulation-induced motor-evoked potentials (TMS-MEPs), and its relationship with UMN burden, is still under investigation.

OBJECTIVE: To evaluate the ability of TMS-MEPs in delineating the neurophysiological UMN damage, and to determine the relationship between TMS-MEPs and [[18]F]FDG-PET measures of neural dysfunction.

METHODS: We retrospectively selected 13 ALS patients who underwent, during the diagnostic process, the TMS-MEPs and [[18]F]FDG-PET scans. Demographic and clinical data were collected. For the MEP evaluation, we considered normal MEP, absent MEP, or significantly increased central-motor-conduction-time. For [[18]F]FDG-PET, we conducted voxel-wise analyses, both at single-subject and group levels, exploring hypometabolism and hypermetabolism patterns in comparison with a large dataset of healthy controls (HC).

RESULTS: Based on TMS-MEPs, we identified 4/13 patients with normal MEP in all limbs (GROUP-NO), while 9/13 had an abnormal MEP in at least one limb (GROUP-AB). Despite the [[18]F]FDG-PET single-subject analysis revealed heterogenous expression of regional hypo- and hyper-metabolism patterns in the patients, the group-level analysis revealed a common hypometabolism, involving the precentral gyrus and the supplementary motor area, the paracentral lobule and the anterior cingulate cortex in the GROUP-AB. Moreover, exclusively for the GROUP-AB compared with HC, a relative hypermetabolism was observed in the right cerebellum, right inferior and middle temporal gyrus. The GROUP-NO showed no specific cluster of hypo- and hyper-metabolism compared to HC.

CONCLUSION: This study showed altered brain metabolism only in the ALS group with abnormal MEPs, suggesting an association between the two biomarkers in defining the UMN damage.}, } @article {pmid38935506, year = {2024}, author = {Halim, DO and Krishnan, G and Hass, EP and Lee, S and Verma, M and Almeida, S and Gu, Y and Kwon, DY and Fazzio, TG and Gao, FB}, title = {The exocyst subunit EXOC2 regulates the toxicity of expanded GGGGCC repeats in C9ORF72-ALS/FTD.}, journal = {Cell reports}, volume = {43}, number = {7}, pages = {114375}, pmid = {38935506}, issn = {2211-1247}, support = {RF1 NS101986/NS/NINDS NIH HHS/United States ; R21 NS119952/NS/NINDS NIH HHS/United States ; R01 HD104971/HD/NICHD NIH HHS/United States ; R37 NS057553/NS/NINDS NIH HHS/United States ; R21 NS112766/NS/NINDS NIH HHS/United States ; R01 NS101986/NS/NINDS NIH HHS/United States ; }, mesh = {*C9orf72 Protein/genetics/metabolism ; Humans ; *Amyotrophic Lateral Sclerosis/genetics/pathology ; *Frontotemporal Dementia/genetics/pathology/metabolism ; *Induced Pluripotent Stem Cells/metabolism ; *DNA Repeat Expansion/genetics ; Motor Neurons/metabolism/pathology ; }, abstract = {GGGGCC (G4C2) repeat expansion in C9ORF72 is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). How this genetic mutation leads to neurodegeneration remains largely unknown. Using CRISPR-Cas9 technology, we deleted EXOC2, which encodes an essential exocyst subunit, in induced pluripotent stem cells (iPSCs) derived from C9ORF72-ALS/FTD patients. These cells are viable owing to the presence of truncated EXOC2, suggesting that exocyst function is partially maintained. Several disease-relevant cellular phenotypes in C9ORF72 iPSC-derived motor neurons are rescued due to, surprisingly, the decreased levels of dipeptide repeat (DPR) proteins and expanded G4C2 repeats-containing RNA. The treatment of fully differentiated C9ORF72 neurons with EXOC2 antisense oligonucleotides also decreases expanded G4C2 repeats-containing RNA and partially rescued disease phenotypes. These results indicate that EXOC2 directly or indirectly regulates the level of G4C2 repeats-containing RNA, making it a potential therapeutic target in C9ORF72-ALS/FTD.}, } @article {pmid38934637, year = {2025}, author = {Tankus, A and Stern, E and Klein, G and Kaptzon, N and Nash, L and Marziano, T and Shamia, O and Gurevitch, G and Bergman, L and Goldstein, L and Fahoum, F and Strauss, I}, title = {A Speech Neuroprosthesis in the Frontal Lobe and Hippocampus: Decoding High-Frequency Activity into Phonemes.}, journal = {Neurosurgery}, volume = {96}, number = {2}, pages = {356-364}, doi = {10.1227/neu.0000000000003068}, pmid = {38934637}, issn = {1524-4040}, support = {17630//Ministry of Science and Technology, Israel/ ; }, mesh = {Humans ; Male ; Adult ; *Hippocampus/physiology ; *Speech/physiology ; *Frontal Lobe/physiology ; Electrodes, Implanted ; *Phonetics ; *Brain-Computer Interfaces ; *Neural Prostheses ; }, abstract = {BACKGROUND AND OBJECTIVES: Loss of speech due to injury or disease is devastating. Here, we report a novel speech neuroprosthesis that artificially articulates building blocks of speech based on high-frequency activity in brain areas never harnessed for a neuroprosthesis before: anterior cingulate and orbitofrontal cortices, and hippocampus.

METHODS: A 37-year-old male neurosurgical epilepsy patient with intact speech, implanted with depth electrodes for clinical reasons only, silently controlled the neuroprosthesis almost immediately and in a natural way to voluntarily produce 2 vowel sounds.

RESULTS: During the first set of trials, the participant made the neuroprosthesis produce the different vowel sounds artificially with 85% accuracy. In the following trials, performance improved consistently, which may be attributed to neuroplasticity. We show that a neuroprosthesis trained on overt speech data may be controlled silently.

CONCLUSION: This may open the way for a novel strategy of neuroprosthesis implantation at earlier disease stages (eg, amyotrophic lateral sclerosis), while speech is intact, for improved training that still allows silent control at later stages. The results demonstrate clinical feasibility of direct decoding of high-frequency activity that includes spiking activity in the aforementioned areas for silent production of phonemes that may serve as a part of a neuroprosthesis for replacing lost speech control pathways.}, } @article {pmid38934512, year = {2024}, author = {Zhang, J and Cao, W and Xie, J and Pang, C and Gao, L and Zhu, L and Li, Y and Yu, H and Du, L and Fan, D and Deng, B}, title = {Metabolic Syndrome and Risk of Amyotrophic Lateral Sclerosis: Insights from a Large-Scale Prospective Study.}, journal = {Annals of neurology}, volume = {96}, number = {4}, pages = {788-801}, doi = {10.1002/ana.27019}, pmid = {38934512}, issn = {1531-8249}, support = {12101460//National Natural Science Foundation of China/ ; 81901273//National Natural Science Foundation of China/ ; LQ21H090018//Natural Science Foundation of Zhejiang Province/ ; LQ22A010005//Natural Science Foundation of Zhejiang Province/ ; LQ22H020003//Natural Science Foundation of Zhejiang Province/ ; ZCLY24H0903//Natural Science Foundation of Zhejiang Province/ ; KY2024-R054//Ethical Decision Committee of the Research Administration at First Affiliated Hospital of Wenzhou Medical University/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/epidemiology ; Male ; Female ; *Metabolic Syndrome/epidemiology ; Middle Aged ; Prospective Studies ; Aged ; Risk Factors ; Adult ; United Kingdom/epidemiology ; Body Mass Index ; Hypertension/epidemiology/complications ; }, abstract = {OBJECTIVE: Although metabolic abnormalities are implicated in the etiology of neurodegenerative diseases, their role in the development of amyotrophic lateral sclerosis (ALS) remains a subject of controversy. We aimed to identify the association between metabolic syndrome (MetS) and the risk of ALS.

METHODS: This study included 395,987 participants from the UK Biobank to investigate the relationship between MetS and ALS. Cox regression model was used to estimate hazard ratios (HR). Stratified analyses were performed based on gender, body mass index (BMI), smoking status, and education level. Mediation analysis was conducted to explore potential mechanisms.

RESULTS: In this study, a total of 539 cases of ALS were recorded after a median follow-up of 13.7 years. Patients with MetS (defined harmonized) had a higher risk of developing ALS after adjusting for confounding factors (HR: 1.50, 95% CI: 1.19-1.89). Specifically, hypertension and high triglycerides were linked to a higher risk of ALS (HR: 1.53, 95% CI: 1.19-1.95; HR: 1.31, 95% CI: 1.06-1.61, respectively). Moreover, the quantity of metabolic abnormalities showed significant results. Stratified analysis revealed that these associations are particularly significant in individuals with a BMI <25. These findings remained stable after sensitivity analysis. Notably, mediation analysis identified potential metabolites and metabolomic mediators, including alkaline phosphatase, cystatin C, γ-glutamyl transferase, saturated fatty acids to total fatty acids percentage, and omega-6 fatty acids to omega-3 fatty acids ratio.

INTERPRETATION: MetS exhibits a robust association with an increased susceptibility to ALS, particularly in individuals with a lower BMI. Furthermore, metabolites and metabolomics, as potential mediators, provide invaluable insights into the intricate biological mechanisms. ANN NEUROL 2024;96:788-801.}, } @article {pmid38934400, year = {2025}, author = {Chen, Y and Wei, Y and Liu, J and Zhu, T and Zhou, C and Zhang, D}, title = {Spatial transcriptomics combined with single-nucleus RNA sequencing reveals glial cell heterogeneity in the human spinal cord.}, journal = {Neural regeneration research}, volume = {20}, number = {11}, pages = {3302-3316}, pmid = {38934400}, issn = {1673-5374}, abstract = {JOURNAL/nrgr/04.03/01300535-202511000-00032/figure1/v/2024-12-20T164640Z/r/image-tiff Glial cells play crucial roles in regulating physiological and pathological functions, including sensation, the response to infection and acute injury, and chronic neurodegenerative disorders. Glial cells include astrocytes, microglia, and oligodendrocytes in the central nervous system, and satellite glial cells and Schwann cells in the peripheral nervous system. Despite the greater understanding of glial cell types and functional heterogeneity achieved through single-cell and single-nucleus RNA sequencing in animal models, few studies have investigated the transcriptomic profiles of glial cells in the human spinal cord. Here, we used high-throughput single-nucleus RNA sequencing and spatial transcriptomics to map the cellular and molecular heterogeneity of astrocytes, microglia, and oligodendrocytes in the human spinal cord. To explore the conservation and divergence across species, we compared these findings with those from mice. In the human spinal cord, astrocytes, microglia, and oligodendrocytes were each divided into six distinct transcriptomic subclusters. In the mouse spinal cord, astrocytes, microglia, and oligodendrocytes were divided into five, four, and five distinct transcriptomic subclusters, respectively. The comparative results revealed substantial heterogeneity in all glial cell types between humans and mice. Additionally, we detected sex differences in gene expression in human spinal cord glial cells. Specifically, in all astrocyte subtypes, the levels of NEAT1 and CHI3L1 were higher in males than in females, whereas the levels of CST3 were lower in males than in females. In all microglial subtypes, all differentially expressed genes were located on the sex chromosomes. In addition to sex-specific gene differences, the levels of MT-ND4 , MT2A , MT-ATP6 , MT-CO3 , MT-ND2 , MT-ND3 , and MT-CO2 in all spinal cord oligodendrocyte subtypes were higher in females than in males. Collectively, the present dataset extensively characterizes glial cell heterogeneity and offers a valuable resource for exploring the cellular basis of spinal cord-related illnesses, including chronic pain, amyotrophic lateral sclerosis, and multiple sclerosis.}, } @article {pmid38934222, year = {2024}, author = {Kim, A and Lee, DY and Sung, JJ}, title = {Cdk5 inhibition in the SOD1[G93A] transgenic mouse model of amyotrophic lateral sclerosis suppresses neurodegeneration and extends survival.}, journal = {Journal of neurochemistry}, volume = {168}, number = {9}, pages = {2908-2925}, doi = {10.1111/jnc.16160}, pmid = {38934222}, issn = {1471-4159}, support = {2018R1A5A2025964//National Research Foundation of Korea/ ; 2019M3C7A1031867//National Research Foundation of Korea/ ; }, mesh = {Animals ; Humans ; Mice ; *Amyotrophic Lateral Sclerosis/genetics/pathology/metabolism ; Cells, Cultured ; *Cyclin-Dependent Kinase 5/metabolism/genetics/antagonists & inhibitors ; Disease Models, Animal ; Mice, Transgenic ; Motor Neurons/pathology/metabolism ; Nerve Degeneration/pathology/genetics/metabolism ; Superoxide Dismutase ; *Superoxide Dismutase-1/genetics ; tau Proteins/metabolism/genetics ; }, abstract = {Deregulated cyclin-dependent kinase 5 (Cdk5) activity closely correlates with hyperphosphorylated tau, a common pathology found in neurodegenerative diseases. Previous postmortem studies had revealed increased Cdk5 immunoreactivity in amyotrophic lateral sclerosis (ALS); hence, we investigated the effects of Cdk5 inhibition on ALS model mice and neurons in this study. For the in vitro study, motor neuron cell lines with wild-type superoxide dismutase 1 (SOD1) or SOD1[G93A] and primary neuronal cultures from SOD1[G93A] transgenic (TG) mice or non-TG mice were compared for the expression of proteins involved in tau pathology, neuroinflammation, apoptosis, and neuritic outgrowth by applying Cdk5-small interfering RNA or Cdk5-short hairpin RNA (shRNA). For the in vivo study, SOD1[G93A] mice and non-TG mice were intrathecally injected with adeno-associated virus 9 (AAV9)-scramble (SCR)-shRNA or AAV9-Cdk5-shRNA at the age of 5 weeks. Weight and motor function were measured three times per week from 60 days of age, longevity was evaluated, and the tissues were collected from 90-day-old or 120-day-old mice. Neurons with SOD1[G93A] showed increased phosphorylated tau, attenuated neuritic growth, mislocalization of SOD1, and enhanced neuroinflammation and apoptosis, all of which were reversed by Cdk5 inhibition. Weights did not show significant differences among non-TG and SOD1[G93A] mice with or without Cdk5 silencing. SOD1[G93A] mice treated with AAV9-Cdk5-shRNA showed significantly delayed disease onset, delayed rotarod failure, and prolonged survival compared with those treated with AAV9-SCR-shRNA. The brain and spinal cord of SOD1[G93A] mice intrathecally injected with AAV9-Cdk5-shRNA exhibited suppressed tau pathology, neuroinflammation, apoptosis, and an increased number of motor neurons compared to those of SOD1[G93A] mice injected with AAV9-SCR-shRNA. Cdk5 inhibition could be an important mechanism in the development of a new therapeutic strategy for ALS.}, } @article {pmid38932502, year = {2024}, author = {Stegmann, G and Krantsevich, C and Liss, J and Charles, S and Bartlett, M and Shefner, J and Rutkove, S and Kawabata, K and Talkar, T and Berisha, V}, title = {Automated speech analytics in ALS: higher sensitivity of digital articulatory precision over the ALSFRS-R.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {25}, number = {7-8}, pages = {767-775}, pmid = {38932502}, issn = {2167-9223}, support = {R01 DC006859/DC/NIDCD NIH HHS/United States ; R43 DC017625/DC/NIDCD NIH HHS/United States ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology/diagnosis/complications ; Male ; Female ; Middle Aged ; Aged ; Speech Disorders/etiology/diagnosis/physiopathology ; Speech/physiology ; Adult ; Speech Production Measurement/methods ; Algorithms ; Severity of Illness Index ; Disease Progression ; }, abstract = {Objective: Although studies have shown that digital measures of speech detected ALS speech impairment and correlated with the ALSFRS-R speech item, no study has yet compared their performance in detecting speech changes. In this study, we compared the performances of the ALSFRS-R speech item and an algorithmic speech measure in detecting clinically important changes in speech. Importantly, the study was part of a FDA submission which received the breakthrough device designation for monitoring ALS; we provide this paper as a roadmap for validating other speech measures for monitoring disease progression. Methods: We obtained ALSFRS-R speech subscores and speech samples from participants with ALS. We computed the minimum detectable change (MDC) of both measures; using clinician-reported listener effort and a perceptual ratings of severity, we calculated the minimal clinically important difference (MCID) of each measure with respect to both sets of clinical ratings. Results: For articulatory precision, the MDC (.85) was lower than both MCID measures (2.74 and 2.28), and for the ALSFRS-R speech item, MDC (.86) was greater than both MCID measures (.82 and .72), indicating that while the articulatory precision measure detected minimal clinically important differences in speech, the ALSFRS-R speech item did not. Conclusion: The results demonstrate that the digital measure of articulatory precision effectively detects clinically important differences in speech ratings, outperforming the ALSFRS-R speech item. Taken together, the results herein suggest that this speech outcome is a clinically meaningful measure of speech change.}, } @article {pmid38932488, year = {2024}, author = {Spencer, D and Polke, J and Campbell, J and Houlden, H and Radunovic, A}, title = {'Outcomes of genetic testing in the London MND Center: the importance of achieving timely results and correlations to family history'.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {25}, number = {7-8}, pages = {737-742}, doi = {10.1080/21678421.2024.2370808}, pmid = {38932488}, issn = {2167-9223}, mesh = {Humans ; Male ; Female ; *Genetic Testing/methods ; London/epidemiology ; Middle Aged ; Aged ; Adult ; Amyotrophic Lateral Sclerosis/genetics/diagnosis ; C9orf72 Protein/genetics ; Superoxide Dismutase-1/genetics ; Mutation/genetics ; Aged, 80 and over ; Genetic Predisposition to Disease/genetics ; Medical History Taking/methods ; }, abstract = {Background: Despite recognition of the importance of genetic factors in the pathogenesis of MND and the increasing availability of genetic testing, testing practice remains highly variable. With the arrival of gene-targeted therapies there is a growing need to promptly identify actionable genetic results and patient death before receipt of results raises ethical dilemmas and limits access to novel therapies. Objective: To identify pathogenic mutations within a London tertiary MND center and their correlation with family history. To record waiting times for genetic results and deaths prior to receipt of results. Methods: In this series of 100 cases, genetic testing was offered to all patients with an MND diagnosis from the tertiary clinic. Data on demographics, disease progression and a detailed family history were taken. Time to receipt of genetic results and patient deaths prior to this were recorded. Results: Of the 97 patients who accepted testing a genetic cause was identified in 10%, including seven C9orf72 and two positive SOD1 cases. Only three patients with positive genetic findings had a family history of MND, although alternative neurological diagnoses and symptoms in the family were frequently reported. 14% of patients who underwent testing were deceased by the time results were received, including one actionable SOD1 case. Conclusions: Genetic testing should be made available to all patients who receive an MND diagnosis as family history alone is inadequate to identify potential familial cases. Time to receipt of results remains a significant issue due to the limited life expectancy following diagnosis.}, } @article {pmid38929462, year = {2024}, author = {De Marchi, I and Buffone, F and Mauro, A and Bruini, I and Vismara, L}, title = {Manual Therapy of Dysphagia in a Patient with Amyotrophic Lateral Sclerosis: A Case Report.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {60}, number = {6}, pages = {}, pmid = {38929462}, issn = {1648-9144}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/complications/therapy ; Male ; *Deglutition Disorders/etiology/therapy ; Middle Aged ; Manipulation, Osteopathic/methods ; Treatment Outcome ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is an incurable rare neurodegenerative condition, with 45% of cases showing the symptom of dysphagia; its clinical signs are atrophy, weakness, and fasciculations of the facial muscles, tongue, and pharynx. Furthermore, dysphagia is the main cause of aspiration pneumonia. The traditional treatment for dysphagia varies based on the patient's difficulty of swallowing. The initial phase consists of dietary consistency adjustments, progressing to alternatives like nasogastric tubes or percutaneous endoscopic gastrostomy (PEG) in advanced stages. Osteopathic manipulative treatment (OMT) is a complementary 'hands-on' approach that has already shown positive results as an add-on therapy in various health conditions. This study is a case report of a man diagnosed with ALS with initial dysphagia, managed with a protocol that extraordinarily included OMT. The patient showed somatic dysfunctions in the mediastinal region, upper cervical region, and occipital area which are all anatomically related to the nervous system, especially the glossopharyngeal reflex. At the end of the rehabilitation protocol, there was a reduction in the swallowing problems measured with Strand Scale and swallowing tests, and the patient reported an improved psycho-physical well-being assessed with the Amyotrophic Lateral Sclerosis Assessment Questionnaire (ALSAQ-40). Instead, the neurological function measured with ALSFRS-S remained stable. Although the nature of this study design prevents any causal assumption, the positive results should lead to future randomized controlled trials to assess the effectiveness of OMT as an adjunctive therapeutic proposal to improve the health of ALS patients.}, } @article {pmid38929429, year = {2024}, author = {Hillaert, A and Sanmiguel Serpa, LC and Xu, Y and Hesta, M and Bogaert, S and Vanderperren, K and Pullens, P}, title = {Optimization of Fair Arterial Spin Labeling Magnetic Resonance Imaging (ASL-MRI) for Renal Perfusion Quantification in Dogs: Pilot Study.}, journal = {Animals : an open access journal from MDPI}, volume = {14}, number = {12}, pages = {}, pmid = {38929429}, issn = {2076-2615}, support = {01D27919//Special Research Fund of Ghent University, Belgium/ ; }, abstract = {Arterial spin labeling (ASL) MRI allows non-invasive quantification of renal blood flow (RBF) and shows great potential for renal assessment. To our knowledge, renal ASL-MRI has not previously been performed in dogs. The aim of this pilot study was to determine parameters essential for ALS-MRI-based quantification of RBF in dogs: T1, blood (longitudinal relaxation time), λ (blood tissue partition coefficient) and TI (inversion time). A Beagle was scanned at 3T with a multi-TI ASL sequence, with TIs ranging from 250 to 2500 ms, to determine the optimal TI value. The T1 of blood for dogs was determined by scanning a blood sample with a 2D IR TSE sequence. The water content of the dog's kidney was determined by analyzing kidney samples from four dogs with a moisture analyzer and was subsequently used to calculate λ. The optimal TI and the measured values for T1,blood, and λ were 2000 ms, 1463 ms and 0.91 mL/g, respectively. These optimized parameters for dogs resulted in lower RBF values than those obtained from inline generated RBF maps. In conclusion, this study determined preliminary parameters essential for ALS-MRI-based RBF quantification in dogs. Further research is needed to confirm these values, but it may help guide future research.}, } @article {pmid38928874, year = {2024}, author = {Szulc, A and Wiśniewska, K and Żabińska, M and Gaffke, L and Szota, M and Olendzka, Z and Węgrzyn, G and Pierzynowska, K}, title = {Effectiveness of Flavonoid-Rich Diet in Alleviating Symptoms of Neurodegenerative Diseases.}, journal = {Foods (Basel, Switzerland)}, volume = {13}, number = {12}, pages = {}, pmid = {38928874}, issn = {2304-8158}, support = {533-0C20-GS0D-24//University of Gdansk/ ; }, abstract = {Over the past decades, there has been a significant increase in the burden of neurological diseases, including neurodegenerative disorders, on a global scale. This is linked to a widespread demographic trend in which developed societies are aging, leading to an increased proportion of elderly individuals and, concurrently, an increase in the number of those afflicted, posing one of the main public health challenges for the coming decades. The complex pathomechanisms of neurodegenerative diseases and resulting varied symptoms, which differ depending on the disease, environment, and lifestyle of the patients, make searching for therapies for this group of disorders a formidable challenge. Currently, most neurodegenerative diseases are considered incurable. An important aspect in the fight against and prevention of neurodegenerative diseases may be broadly understood lifestyle choices, and more specifically, what we will focus on in this review, a diet. One proposal that may help in the fight against the spread of neurodegenerative diseases is a diet rich in flavonoids. Flavonoids are compounds widely found in products considered healthy, such as fruits, vegetables, and herbs. Many studies indicated not only the neuroprotective effects of these compounds but also their ability to reverse changes occurring during the progression of diseases such as Alzheimer's, Parkinson's and amyotrophic lateral sclerosis. Here, we present the main groups of flavonoids, discussing their characteristics and mechanisms of action. The most widely described mechanisms point to neuroprotective functions due to strong antioxidant and anti-inflammatory effects, accompanied with their ability to penetrate the blood-brain barrier, as well as the ability to inhibit the formation of protein aggregates. The latter feature, together with promoting removal of the aggregates is especially important in neurodegenerative diseases. We discuss a therapeutic potential of selected flavonoids in the fight against neurodegenerative diseases, based on in vitro studies, and their impact when included in the diet of animals (laboratory research) and humans (population studies). Thus, this review summarizes flavonoids' actions and impacts on neurodegenerative diseases. Therapeutic use of these compounds in the future is potentially possible but depends on overcoming key challenges such as low bioavailability, determining the therapeutic dose, and defining what a flavonoid-rich diet is and determining its potential negative effects. This review also suggests further research directions to address these challenges.}, } @article {pmid38928564, year = {2024}, author = {Lin, CY and Vanoverbeke, V and Trent, D and Willey, K and Lee, YS}, title = {The Spatiotemporal Expression of SOCS3 in the Brainstem and Spinal Cord of Amyotrophic Lateral Sclerosis Mice.}, journal = {Brain sciences}, volume = {14}, number = {6}, pages = {}, pmid = {38928564}, issn = {2076-3425}, support = {2022-040//Cleveland Clinic Technology Development Investment Project and Ohio Third Frontier Technology Validation and Start-up Fund/ ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is characterized by the progressive loss of motor neurons from the brain and spinal cord. The excessive neuroinflammation is thought to be a common determinant of ALS. Suppressor of cytokine signaling-3 (SOCS3) is pathologically upregulated after injury/diseases to negatively regulate a broad range of cytokines/chemokines that mediate inflammation; however, the role that SOCS3 plays in ALS pathogenesis has not been explored. Here, we found that SOCS3 protein levels were significantly increased in the brainstem of the superoxide dismutase 1 (SOD1)-G93A ALS mice, which is negatively related to a progressive decline in motor function from the pre-symptomatic to the early symptomatic stage. Moreover, SOCS3 levels in both cervical and lumbar spinal cords of ALS mice were also significantly upregulated at the pre-symptomatic stage and became exacerbated at the early symptomatic stage. Concomitantly, astrocytes and microglia/macrophages were progressively increased and reactivated over time. In contrast, neurons were simultaneously lost in the brainstem and spinal cord examined over the course of disease progression. Collectively, SOCS3 was first found to be upregulated during ALS progression to directly relate to both increased astrogliosis and increased neuronal loss, indicating that SOCS3 could be explored to be as a potential therapeutic target of ALS.}, } @article {pmid38928553, year = {2024}, author = {Di Martino, P and Marcozzi, V and Bibbò, S and Ghinassi, B and Di Baldassarre, A and Gaggi, G and Di Credico, A}, title = {Unraveling the Epigenetic Landscape: Insights into Parkinson's Disease, Amyotrophic Lateral Sclerosis, and Multiple Sclerosis.}, journal = {Brain sciences}, volume = {14}, number = {6}, pages = {}, pmid = {38928553}, issn = {2076-3425}, support = {MUR-Fondo Promozione e Sviluppo-DM 737/2021, DEFENDANTs, Developmental Neurotoxi-city of Endocrine Disruptors from Plastic Pollutants.//NextGenerationEU "MUR-Fondo Promozione e Sviluppo-DM 737/2021, DEFENDANTs, De-velopmental Neurotoxicity of Endocrine Disruptors from Plastic Pollutants./ ; }, abstract = {Parkinson's disease (PD), multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS) are examples of neurodegenerative movement disorders (NMDs), which are defined by a gradual loss of motor function that is frequently accompanied by cognitive decline. Although genetic abnormalities have long been acknowledged as significant factors, new research indicates that epigenetic alterations are crucial for the initiation and development of disease. This review delves into the complex interactions that exist between the pathophysiology of NMDs and epigenetic mechanisms such DNA methylation, histone modifications, and non-coding RNAs. Here, we examine how these epigenetic changes could affect protein aggregation, neuroinflammation, and gene expression patterns, thereby influencing the viability and functionality of neurons. Through the clarification of the epigenetic terrain underpinning neurodegenerative movement disorders, this review seeks to enhance comprehension of the underlying mechanisms of the illness and augment the creation of innovative therapeutic strategies.}, } @article {pmid38927681, year = {2024}, author = {Adler, GL and Le, K and Fu, Y and Kim, WS}, title = {Human Endogenous Retroviruses in Neurodegenerative Diseases.}, journal = {Genes}, volume = {15}, number = {6}, pages = {}, pmid = {38927681}, issn = {2073-4425}, mesh = {Humans ; *Endogenous Retroviruses/genetics/pathogenicity ; *Neurodegenerative Diseases/virology/genetics ; Amyotrophic Lateral Sclerosis/virology/genetics ; Animals ; }, abstract = {Human endogenous retroviruses (HERVs) are DNA transposable elements that have integrated into the human genome via an ancestral germline infection. The potential importance of HERVs is underscored by the fact that they comprise approximately 8% of the human genome. HERVs have been implicated in the pathogenesis of neurodegenerative diseases, a group of CNS diseases characterized by a progressive loss of structure and function of neurons, resulting in cell death and multiple physiological dysfunctions. Much evidence indicates that HERVs are initiators or drivers of neurodegenerative processes in multiple sclerosis and amyotrophic lateral sclerosis, and clinical trials have been designed to target HERVs. In recent years, the role of HERVs has been explored in other major neurodegenerative diseases, including frontotemporal dementia, Alzheimer's disease and Parkinson's disease, with some interesting discoveries. This review summarizes and evaluates the past and current research on HERVs in neurodegenerative diseases. It discusses the potential role of HERVs in disease manifestation and neurodegeneration. It critically reviews antiretroviral strategies used in the therapeutic intervention of neurodegenerative diseases.}, } @article {pmid38927674, year = {2024}, author = {Gotte, G}, title = {Effects of Pathogenic Mutants of the Neuroprotective RNase 5-Angiogenin in Amyotrophic Lateral Sclerosis (ALS).}, journal = {Genes}, volume = {15}, number = {6}, pages = {}, pmid = {38927674}, issn = {2073-4425}, mesh = {*Amyotrophic Lateral Sclerosis/genetics/pathology ; Humans ; *Ribonuclease, Pancreatic/genetics/metabolism ; *Motor Neurons/metabolism/pathology ; Animals ; Mutation ; }, abstract = {Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease that affects the motoneurons. More than 40 genes are related with ALS, and amyloidogenic proteins like SOD1 and/or TDP-43 mutants are directly involved in the onset of ALS through the formation of polymorphic fibrillogenic aggregates. However, efficacious therapeutic approaches are still lacking. Notably, heterozygous missense mutations affecting the gene coding for RNase 5, an enzyme also called angiogenin (ANG), were found to favor ALS onset. This is also true for the less-studied but angiogenic RNase 4. This review reports the substrate targets and illustrates the neuroprotective role of native ANG in the neo-vascularization of motoneurons. Then, it discusses the molecular determinants of many pathogenic ANG mutants, which almost always cause loss of function related to ALS, resulting in failures in angiogenesis and motoneuron protection. In addition, ANG mutations are sometimes combined with variants of other factors, thereby potentiating ALS effects. However, the activity of the native ANG enzyme should be finely balanced, and not excessive, to avoid possible harmful effects. Considering the interplay of these angiogenic RNases in many cellular processes, this review aims to stimulate further investigations to better elucidate the consequences of mutations in ANG and/or RNase 4 genes, in order to achieve early diagnosis and, possibly, successful therapies against ALS.}, } @article {pmid38927671, year = {2024}, author = {Carata, E and Muci, M and Mariano, S and Di Giulio, S and Nigro, A and Romano, A and Panzarini, E}, title = {Extracellular Vesicles from NSC-34 MN-like Cells Transfected with Mutant SOD1 Modulate Inflammatory Status of Raw 264.7 Macrophages.}, journal = {Genes}, volume = {15}, number = {6}, pages = {}, pmid = {38927671}, issn = {2073-4425}, mesh = {Animals ; *Extracellular Vesicles/metabolism/genetics ; Mice ; RAW 264.7 Cells ; *Superoxide Dismutase-1/genetics/metabolism ; *Macrophages/metabolism ; *Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology ; *Motor Neurons/metabolism ; Inflammation/genetics/metabolism/pathology ; Mutation ; Transfection ; Humans ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease targeting the brain and spinal cord. Non-neuronal cells, including macrophages, may contribute to the disruption of motor neurons (MNs), neuromuscular junction dismantling and clinical signs of ALS. Understanding the modality and the effect of MNs-macrophage communication is pivotal. Here, we focus on extracellular vesicle (EVS)-mediated communication and, in particular, we analyze the response of macrophages. NSC-34 cells transfected with mutant SOD1 (G93A, A4V, G85R, G37R) and differentiated towards MN-like cells, and Raw 264.7 macrophages are the cellular models of the study. mSOD1 NSC-34 cells release a high number of vesicles, both large-lEVs (300 nm diameter) and small-sEVs (90 nm diameter), containing inflammation-modulating molecules, and are efficiently taken up by macrophages. RT-PCR analysis of inflammation mediators demonstrated that the conditioned medium of mSOD1 NSC-34 cells polarizes Raw 264.7 macrophages towards both pro-inflammatory and anti-inflammatory phenotypes. sEVs act on macrophages in a time-dependent manner: an anti-inflammatory response mediated by TGFβ firstly starts (12 h); successively, the response shifts towards a pro-inflammation IL-1β-mediated (48 h). The response of macrophages is strictly dependent on the SOD1 mutation type. The results suggest that EVs impact physiological and behavioral macrophage processes and are of potential relevance to MN degeneration.}, } @article {pmid38927616, year = {2024}, author = {Wang, H and Guan, L and Ma, X and Wang, Y and Wang, J and Zhang, P and Deng, M}, title = {Whole-Genome Sequencing Identified a Novel Mutation in the N-Terminal Domain of KIF5A in Chinese Patients with Familial Amyotrophic Lateral Sclerosis.}, journal = {Genes}, volume = {15}, number = {6}, pages = {}, pmid = {38927616}, issn = {2073-4425}, support = {82273915//National Natural Science Foundation of China/ ; }, mesh = {Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; *Amyotrophic Lateral Sclerosis/genetics/pathology ; China ; East Asian People/genetics ; *Kinesins/genetics ; Mutation ; *Mutation, Missense ; Pedigree ; Phenotype ; *Whole Genome Sequencing ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder characterized by progressive damage to both upper and lower motor neurons. Genetic factors are known to play a crucial role in ALS, as genetic studies not only advance our comprehension of disease mechanisms but also help unravel the complex phenotypes exhibited by patients. To gain further insights into the genetic landscape of ALS in the Chinese population and explore genotype-phenotype correlations among individuals, we conducted whole-genome sequencing to screen genes in 34 Chinese familial ALS (FALS) probands lacking the most common ALS-associated genes. Within this cohort, we identified a rare heterozygous missense mutation in the N-terminal domain of KIF5A (c.86A>G) in one of the probands. This finding is significant as mutations in the KIF5A gene have been implicated in ALS in European cohorts since 2018, predominantly characterized by C-terminal mutations. Analysis of the clinical phenotype within this familial lineage revealed a delayed onset of symptoms, an extended survival duration, and initial manifestations in both upper limbs. These observations underscore the clinical heterogeneity observed in ALS patients harboring KIF5A mutations. In conclusion, our study contributes to the growing body of evidence linking KIF5A to ALS and enhances our understanding of the intricate genetic landscape of this disease.}, } @article {pmid38927501, year = {2024}, author = {Parvanovova, P and Evinova, A and Grofik, M and Hnilicova, P and Tatarkova, Z and Turcanova-Koprusakova, M}, title = {Mitochondrial Dysfunction in Sporadic Amyotrophic Lateral Sclerosis Patients: Insights from High-Resolution Respirometry.}, journal = {Biomedicines}, volume = {12}, number = {6}, pages = {}, pmid = {38927501}, issn = {2227-9059}, abstract = {Amyotrophic lateral sclerosis is a severe neurodegenerative disease whose exact cause is still unclear. Currently, research attention is turning to the mitochondrion as a critical organelle of energy metabolism. Current knowledge is sufficient to confirm the involvement of the mitochondria in the pathophysiology of the disease, since the mitochondria are involved in many processes in the cell; however, the exact mechanism of involvement is still unclear. We used peripheral blood mononuclear cells isolated from whole fresh blood from patients with amyotrophic lateral sclerosis for measurement and matched an age- and sex-matched set of healthy subjects. The group of patients consisted of patients examined and diagnosed at the neurological clinic of the University Hospital Martin. The set of controls consisted of healthy individuals who were actively searched, and controls were selected on the basis of age and sex. The group consisted of 26 patients with sporadic forms of ALS (13 women, 13 men), diagnosed based on the definitive criteria of El Escorial. The average age of patients was 54 years, and the average age of healthy controls was 56 years. We used a high-resolution O2K respirometry method, Oxygraph-2k, to measure mitochondrial respiration. Basal respiration was lower in patients by 29.48%, pyruvate-stimulated respiration (respiratory chain complex I) was lower by 29.26%, and maximal respiratory capacity was lower by 28.15%. The decrease in succinate-stimulated respiration (respiratory chain complex II) was 26.91%. Our data confirm changes in mitochondrial respiration in ALS patients, manifested by the reduced function of complex I and complex II of the respiratory chain. These defects are severe enough to confirm this disease's hypothesized mitochondrial damage. Therefore, research interest in the future should be directed towards a deeper understanding of the involvement of mitochondria and respiratory complexes in the pathophysiology of the disease. This understanding could develop new biomarkers in diagnostics and subsequent therapeutic interventions.}, } @article {pmid38927130, year = {2024}, author = {Vilardo, B and De Marchi, F and Raineri, D and Manfredi, M and De Giorgis, V and Bebeti, A and Scotti, L and Kustrimovic, N and Cappellano, G and Mazzini, L and Chiocchetti, A}, title = {Shotgun Proteomics Links Proteoglycan-4[+] Extracellular Vesicles to Cognitive Protection in Amyotrophic Lateral Sclerosis.}, journal = {Biomolecules}, volume = {14}, number = {6}, pages = {}, pmid = {38927130}, issn = {2218-273X}, support = {953121//European Union's Horizon 2020 Research and Innovation Program/ ; FOHN//Ministero dell'Istruzione e del Merito/ ; AGING//Ministero dell'Istruzione e del Merito/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism/blood ; *Extracellular Vesicles/metabolism ; *Proteomics/methods ; Male ; Middle Aged ; Female ; *Biomarkers/blood/metabolism ; Aged ; Proteoglycans/metabolism ; Cognition ; Case-Control Studies ; Adult ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder lacking reliable biomarkers for early diagnosis and disease progression monitoring. This study aimed to identify the novel biomarkers in plasmatic extracellular vesicles (EVs) isolated from ALS patients and healthy controls (HCs). A total of 61 ALS patients and 30 age-matched HCs were enrolled in the study and the protein content of circulating EVs was analyzed by shotgun proteomics. The study was divided into a discovery phase (involving 12 ALS and 12 HC patients) and a validation one (involving 49 ALS and 20 HC patients). In the discovery phase, more than 300 proteins were identified, with 32 proteins showing differential regulation in ALS patients compared to HCs. In the validation phase, over 400 proteins were identified, with 20 demonstrating differential regulation in ALS patients compared to HCs. Notably, seven proteins were found to be common to both phases, all of which were significantly upregulated in EVs from ALS patients. Most of them have previously been linked to ALS since they have been detected in the serum or cerebrospinal fluid of ALS patients. Among them, proteoglycan (PRG)-4, also known as lubricin, was of particular interest since it was significantly increased in ALS patients with normal cognitive and motor functions. This study highlights the significance of EVs as a promising avenue for biomarker discovery in ALS. Moreover, it sheds light on the unexpected role of PRG-4 in relation to cognitive status in ALS patients.}, } @article {pmid38926444, year = {2024}, author = {Bhuyan, P and Chatterjee, K}, title = {Estimating prevalence of post-war health disorders using multiple systems data.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {14763}, pmid = {38926444}, issn = {2045-2322}, support = {Category-I Research Project Grant (No. 3878/RP: PSEISMC-RDA HIVS)//Indian Institute of Management Calcutta/ ; Core Research Grant (No. CRG/2019/003204)//Science and Engineering Research Board (SERB), Department of Science & Technology, Government of India/ ; }, mesh = {Humans ; Prevalence ; *Amyotrophic Lateral Sclerosis/epidemiology ; Veterans/statistics & numerical data ; Algorithms ; Monte Carlo Method ; Gulf War ; }, abstract = {Effective surveillance on the long-term public health impact due to war and terrorist attacks remains limited. Such health issues are commonly under-reported, specifically for a large group of individuals. For this purpose, efficient estimation of the size or undercount of the population under the risk of physical and mental health hazards is of utmost necessity. A novel trivariate Bernoulli model is developed allowing heterogeneity among the individuals and dependence between the sources of information, and an estimation methodology using a Monte Carlo-based EM algorithm is proposed. Simulation results show the superiority of the performance of the proposed method over existing competitors and robustness under model mis-specifications. The method is applied to analyse two real case studies on monitoring amyotrophic lateral sclerosis (ALS) cases for the Gulf War veterans and the 9/11 terrorist attack survivors at the World Trade Center, USA. The average annual cumulative incidence rate for ALS disease increases by 33 % and 16 % for deployed and no-deployed military personnel, respectively, after adjusting the undercount. The number of individuals exposed to the risk of physical and mental health effects due to WTC terrorist attacks increased by 42 % . These results provide interesting insights that can assist in effective decision-making and policy formulation for monitoring the health status of post-war survivors.}, } @article {pmid38925911, year = {2024}, author = {De La Cruz, E and Esselin, F and Polge, A and Mouzat, K and Guissart, C}, title = {Most SOD1 mutations are pathogenic, and their identification can lead to early access to treatment.}, journal = {Journal of neurology, neurosurgery, and psychiatry}, volume = {95}, number = {12}, pages = {1219-1220}, doi = {10.1136/jnnp-2024-333939}, pmid = {38925911}, issn = {1468-330X}, } @article {pmid38925110, year = {2024}, author = {Wyse-Sookoo, K and Luo, S and Candrea, D and Schippers, A and Tippett, DC and Wester, B and Fifer, M and Vansteensel, MJ and Ramsey, NF and Crone, NE}, title = {Stability of ECoG high gamma signals during speech and implications for a speech BCI system in an individual with ALS: a year-long longitudinal study.}, journal = {Journal of neural engineering}, volume = {21}, number = {4}, pages = {}, pmid = {38925110}, issn = {1741-2552}, support = {T32 EB003383/EB/NIBIB NIH HHS/United States ; UH3 NS114439/NS/NINDS NIH HHS/United States ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology ; *Brain-Computer Interfaces ; Longitudinal Studies ; *Electrocorticography/methods ; *Speech/physiology ; Male ; Gamma Rhythm/physiology ; Middle Aged ; Female ; Electrodes, Implanted ; }, abstract = {Objective.Speech brain-computer interfaces (BCIs) have the potential to augment communication in individuals with impaired speech due to muscle weakness, for example in amyotrophic lateral sclerosis (ALS) and other neurological disorders. However, to achieve long-term, reliable use of a speech BCI, it is essential for speech-related neural signal changes to be stable over long periods of time. Here we study, for the first time, the stability of speech-related electrocorticographic (ECoG) signals recorded from a chronically implanted ECoG BCI over a 12 month period.Approach.ECoG signals were recorded by an ECoG array implanted over the ventral sensorimotor cortex in a clinical trial participant with ALS. Because ECoG-based speech decoding has most often relied on broadband high gamma (HG) signal changes relative to baseline (non-speech) conditions, we studied longitudinal changes of HG band power at baseline and during speech, and we compared these with residual high frequency noise levels at baseline. Stability was further assessed by longitudinal measurements of signal-to-noise ratio, activation ratio, and peak speech-related HG response magnitude (HG response peaks). Lastly, we analyzed the stability of the event-related HG power changes (HG responses) for individual syllables at each electrode.Main Results.We found that speech-related ECoG signal responses were stable over a range of syllables activating different articulators for the first year after implantation.Significance.Together, our results indicate that ECoG can be a stable recording modality for long-term speech BCI systems for those living with severe paralysis.Clinical Trial Information.ClinicalTrials.gov, registration number NCT03567213.}, } @article {pmid38924779, year = {2024}, author = {Bratches, RWR and Cohen, J and Carpenter-Song, E and Mistler, L and Barr, PJ}, title = {The Feasibility and Acceptability of Sharing Video Recordings of Amyotrophic Lateral Sclerosis Clinical Encounters With Patients and Their Caregivers: Pilot Randomized Clinical Trial.}, journal = {JMIR formative research}, volume = {8}, number = {}, pages = {e57519}, pmid = {38924779}, issn = {2561-326X}, support = {T32 HS013852/HS/AHRQ HHS/United States ; }, abstract = {BACKGROUND: Multidisciplinary clinics (MDCs) provide benefits to patients with amyotrophic lateral sclerosis (ALS) and their caregivers, but MDC visits are information-heavy and can last 4 hours, with patients and caregivers meeting with multiple specialists within each MDC visit. There are questions about the effectiveness of current methods of sharing information from MDCs with patients. Video recordings are a promising new method of sharing information that may allow patients and caregivers to revisit the MDC and remind them of clinical recommendations and conversations.

OBJECTIVE: The objective of this trial is to determine the feasibility and acceptability of sharing information through video recordings of ALS MDC visits with patients and caregivers.

METHODS: This study was a randomized, controlled pilot trial with 3 months of follow-up from April 2021 to March 2022 in a rural multidisciplinary neurology clinic. We recruited patients with ALS, their caregivers, and their clinicians. Patients and their caregivers were randomized to either receive their normal after-visit summary (treatment as usual) or to receive their normal after-visit summary and a video recording of their MDC visit (video). Each specialist visit had its own recording and was accessible by patients and caregivers using a secure web-based platform called HealthPAL over a 3-month follow-up period. Primary study outcomes were feasibility and acceptability of the video intervention measured by recruitment rate (target: 70%), percentage of participants watching videos (target: 75%), and the Feasibility of Intervention Measure and Acceptability of Intervention Measure (targets: 3/5). We hypothesized that video recording would be feasible and acceptable to patients and their caregivers.

RESULTS: Of the 30 patients approached, 24 were recruited, while all caregivers (n=21) and clinicians (n=34) approached were recruited. A total of 144 specialist visits were recorded, approximately 12 specialist visits at a median of one MDC visit per patient. Of the recorded patients, 75% (9/12) viewed videos. High median intervention feasibility (4, SD 0.99) and acceptability (4, SD 1.22) of intervention measures were reported by patients and caregivers in the intervention arm. High median intervention feasibility (5, SD 0.21) and acceptability (4.88, SD 0.4) were reported by clinicians. Of the 24 patients, 50% (n=12) did not complete a 3-month follow-up, primarily due to death (n=10).

CONCLUSIONS: Video recording is highly feasible and acceptable for patients, caregivers, and clinicians at a rural ALS clinic. Our level of attrition is a useful benchmark for future studies in MDC populations. Despite high rates of patient death, 1-week assessments highlight the value of recordings for both patients and caregivers.

TRIAL REGISTRATION: ClinicalTrials.gov NCT04719403; https://clinicaltrials.gov/study/NCT04719403.}, } @article {pmid38924719, year = {2024}, author = {Shaw, PJ and Cooper-Knock, J}, title = {Physical Activity as a Risk Factor for Amyotrophic Lateral Sclerosis.}, journal = {Neurology}, volume = {103}, number = {2}, pages = {e209689}, doi = {10.1212/WNL.0000000000209689}, pmid = {38924719}, issn = {1526-632X}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/epidemiology ; Risk Factors ; *Exercise ; }, } @article {pmid38924713, year = {2024}, author = {Vaage, AM and Meyer, HE and Landgraff, IK and Myrstad, M and Holmøy, T and Nakken, O}, title = {Physical Activity, Fitness, and Long-Term Risk of Amyotrophic Lateral Sclerosis: A Prospective Cohort Study.}, journal = {Neurology}, volume = {103}, number = {2}, pages = {e209575}, doi = {10.1212/WNL.0000000000209575}, pmid = {38924713}, issn = {1526-632X}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/epidemiology/physiopathology ; Male ; Female ; Adult ; Middle Aged ; Prospective Studies ; Norway/epidemiology ; *Physical Fitness/physiology ; Risk Factors ; Heart Rate/physiology ; Exercise/physiology ; Cohort Studies ; Proportional Hazards Models ; Motor Activity/physiology ; }, abstract = {BACKGROUND AND OBJECTIVES: Observational studies have demonstrated an increased amyotrophic lateral sclerosis (ALS) risk among professional athletes in various sports. For moderately increased levels of physical activity and fitness, the results are diverging. Through a cohort study, we aimed to assess the relationship between indicators of physical activity and fitness (self-reported physical activity and resting heart rate) and long-term ALS risk.

METHODS: From a large Norwegian cardiovascular health survey (1985-1999), we collected information on self-reported physical activity in leisure time, resting heart rate, and other cardiovascular risk factors. Patients with ALS were identified through health registries covering the whole population. We fitted Cox proportional hazard models to assess the risk of ALS according to levels of self-reported physical activity in 3 categories (1: sedentary; 2: minimum 4 hours per week of walking or cycling; 3: minimum 4 hours per week of recreational sports or hard training), and resting heart rate modeled both on the continuous scale and as quartiles of distribution.

RESULTS: Out of 373,696 study participants (mean 40.9 [SD 1.1] years at inclusion), 504 (41.2% women) developed ALS during a mean follow-up time of 27.2 (SD 5.0) years. Compared with participants with the lowest level of physical activity, the hazard ratio was 0.71 (95% CI 0.53-0.95) for those with the highest level. There were no clear associations between resting heart rate and ALS in the total sample. In men, the hazard ratio of ALS was 0.71 (95% CI 0.53-0.95) for those reporting moderate levels of physical activity and 0.59 (95% CI 0.42-0.84) for those reporting high levels, compared with those reporting low levels. Men with resting heart rate in the lowest quartile had 32% reduced risk of ALS (hazard ratio 0.68, 95% CI 0.49-0.94) compared with those in the second highest quartile. In women, no association was detected between neither self-reported levels of physical activity nor resting heart rate and ALS risk.

DISCUSSION: Indicators of high levels of physical activity and fitness are associated with a reduced risk of ALS more than 30 years later in men, but not in women.}, } @article {pmid38924633, year = {2024}, author = {Wolf, J and Buckley, GJ and Rozanski, EA and Fletcher, DJ and Boller, M and Burkitt-Creedon, JM and Weigand, KA and Crews, M and Fausak, ED and , }, title = {2024 RECOVER Guidelines: Advanced Life Support. Evidence and knowledge gap analysis with treatment recommendations for small animal CPR.}, journal = {Journal of veterinary emergency and critical care (San Antonio, Tex. : 2001)}, volume = {34 Suppl 1}, number = {}, pages = {44-75}, doi = {10.1111/vec.13389}, pmid = {38924633}, issn = {1476-4431}, support = {//Zoetis Animal Health/ ; //Boehringer Ingelheim Animal Health/ ; }, mesh = {Animals ; Dogs ; Cats ; *Dog Diseases/therapy/drug therapy ; Cardiopulmonary Resuscitation/veterinary/standards ; Cat Diseases/therapy/drug therapy ; Veterinary Medicine/standards ; Heart Arrest/veterinary/therapy ; }, abstract = {OBJECTIVE: To systematically review the evidence and devise clinical recommendations on advanced life support (ALS) in dogs and cats and to identify critical knowledge gaps.

DESIGN: Standardized, systematic evaluation of literature pertinent to ALS following Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. Prioritized questions were each reviewed by Evidence Evaluators, and findings were reconciled by ALS Domain Chairs and Reassessment Campaign on Veterinary Resuscitation (RECOVER) Co-Chairs to arrive at treatment recommendations commensurate to quality of evidence, risk:benefit relationship, and clinical feasibility. This process was implemented using an Evidence Profile Worksheet for each question that included an introduction, consensus on science, treatment recommendations, justification for these recommendations, and important knowledge gaps. A draft of these worksheets was distributed to veterinary professionals for comment for 4 weeks prior to finalization.

SETTING: Transdisciplinary, international collaboration in university, specialty, and emergency practice.

RESULTS: Seventeen questions pertaining to vascular access, vasopressors in shockable and nonshockable rhythms, anticholinergics, defibrillation, antiarrhythmics, and adjunct drug therapy as well as open-chest CPR were reviewed. Of the 33 treatment recommendations formulated, 6 recommendations addressed the management of patients with nonshockable arrest rhythms, 10 addressed shockable rhythms, and 6 provided guidance on open-chest CPR. We recommend against high-dose epinephrine even after prolonged CPR and suggest that atropine, when indicated, is used only once. In animals with a shockable rhythm in which initial defibrillation was unsuccessful, we recommend doubling the defibrillator dose once and suggest vasopressin (or epinephrine if vasopressin is not available), esmolol, lidocaine in dogs, and/or amiodarone in cats.

CONCLUSIONS: These updated RECOVER ALS guidelines clarify the approach to refractory shockable rhythms and prolonged CPR. Very low quality of evidence due to absence of clinical data in dogs and cats continues to compromise the certainty with which recommendations can be made.}, } @article {pmid38924627, year = {2024}, author = {Burkitt-Creedon, JM and Boller, M and Fletcher, DJ and Brainard, BM and Buckley, GJ and Epstein, SE and Fausak, ED and Hopper, K and Lane, SL and Rozanski, EA and Wolf, J}, title = {2024 RECOVER Guidelines: Updated treatment recommendations for CPR in dogs and cats.}, journal = {Journal of veterinary emergency and critical care (San Antonio, Tex. : 2001)}, volume = {34 Suppl 1}, number = {}, pages = {104-123}, doi = {10.1111/vec.13391}, pmid = {38924627}, issn = {1476-4431}, support = {//Boehringer Ingelheim Animal Health/ ; //Zoetis Animal Health/ ; }, mesh = {Dogs ; Animals ; Cats ; *Cardiopulmonary Resuscitation/veterinary/standards/methods ; *Cat Diseases/therapy ; Dog Diseases/therapy ; Heart Arrest/veterinary/therapy ; }, abstract = {OBJECTIVE: After the 2012 Reassessment Campaign on Veterinary Resuscitation (RECOVER) CPR Guidelines, this is an update of evidence-based consensus guidelines for Basic Life Support (BLS), advanced life support (ALS), and periarrest monitoring.

DESIGN: These RECOVER CPR Guidelines were generated using a modified version of the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system for evidence evaluation and translation of this evidence into clear and actionable clinical instructions. Prioritized clinical questions in the Population, Intervention, Comparator, and Outcome (PICO) format were used as the basis to conduct systematic literature searches by information specialists, to extract information from relevant publications, to assess this evidence for quality, and finally to translate the findings into treatment recommendations. These recommendations were reviewed by the RECOVER writing group and opened for comment by veterinary professionals for 4 weeks.

SETTING: Transdisciplinary, international collaboration in university, specialty, and emergency practice.

RESULTS: A total of 40 worksheets were prepared to evaluate questions across the 3 domains of BLS, ALS and Monitoring, resulting in 90 individual treatment recommendations. High-dose epinephrine is no longer recommended, and atropine, if used, is only administered once. Bag-mask ventilation is prioritized over mouth-to-nose ventilation in nonintubated animals. In addition, an algorithm for initial assessment, an updated CPR algorithm, a rhythm diagnosis tool, and an updated drug dosing table are provided.

CONCLUSIONS: While the majority of the BLS and ALS recommendations remain unchanged, some noteworthy changes were made due to new evidence that emerged over the past 10 years. Indirectness of evidence remains the largest impediment to the certainty of guidelines formulation and underscores an urgent need for more studies in the target species of dogs and cats.}, } @article {pmid38924530, year = {2024}, author = {Deutsch, AJ and Elbasiouny, SM}, title = {Dysregulation of persistent inward and outward currents in spinal motoneurons of symptomatic SOD1-G93A mice.}, journal = {The Journal of physiology}, volume = {602}, number = {15}, pages = {3715-3736}, pmid = {38924530}, issn = {1469-7793}, support = {NS131816-S2/NS/NINDS NIH HHS/United States ; R01 NS131816/NS/NINDS NIH HHS/United States ; AG067758/AG/NIA NIH HHS/United States ; NS091836/NS/NINDS NIH HHS/United States ; R01 NS091836/NS/NINDS NIH HHS/United States ; NS131816/NS/NINDS NIH HHS/United States ; R01 AG067758/AG/NIA NIH HHS/United States ; }, mesh = {Animals ; *Motor Neurons/physiology ; *Amyotrophic Lateral Sclerosis/physiopathology/genetics/pathology ; Mice ; *Mice, Transgenic ; Spinal Cord/physiology ; Superoxide Dismutase-1/genetics ; Male ; Female ; Mice, Inbred C57BL ; Action Potentials ; }, abstract = {Persistent inward currents (PICs) and persistent outward currents (POCs) regulate the excitability and firing behaviours of spinal motoneurons (MNs). Given their potential role in MN excitability dysfunction in amyotrophic lateral sclerosis (ALS), PICs have been previously studied in superoxide dismutase 1 (SOD1)-G93A mice (the standard animal model of ALS); however, conflicting results have been reported on how the net PIC changes during disease progression. Also, individual PICs and POCs have never been examined before in symptomatic ALS. To fill this gap, we measured the net and individual PIC and POC components of wild-type (WT) and SOD MNs in current clamp and voltage clamp during disease progression (assessed by neuroscores). We show that SOD MNs of symptomatic mice experience a much larger net PIC, relative to WT cells from age-matched littermates. Specifically, the Na[+] and Ca[2+] PICs are larger, whereas the lasting SK-mediated (SKL) POC is smaller than WT (Na[+] PIC is the largest and SKL POC is the smallest components in SOD MNs). We also show that PIC dysregulation is present at symptom onset, is sustained throughout advanced disease stages and is proportional to SOD MN cell size (largest dysregulation is in the largest SOD cells, the most vulnerable in ALS). Additionally, we show that studying disease progression using neuroscores is more accurate than using SOD mouse age, which could lead to misleading statistics and age-based trends. Collectively, this study contributes novel PIC and POC data, reveals ionic mechanisms contributing to the vulnerability differential among MN types/sizes, and provides insights on the roles PIC and POC mechanisms play in MN excitability dysfunction in ALS. KEY POINTS: Individual persistent inward currents (PICs) and persistent outward currents (POCs) have never been examined before in spinal motoneurons (MNs) of symptomatic amyotrophic lateral sclerosis (ALS) mice. Thus, we contribute novel PIC and POC data to the ALS literature. Male SOD MNs of symptomatic mice have elevated net PIC, with larger Na[+] and Ca[2+] PICs but reduced SKL POC vs. wild-type littermates. Na[+] PIC is the largest and SKL POC is the smallest current in SOD cells. The PIC/POC dysregulation is present at symptom onset. PIC dysregulation is sustained throughout advanced disease, and is proportional to SOD MN size (largest dysregulation is in the largest cells, the most vulnerable in ALS). Thus, we reveal ionic mechanisms contributing to the vulnerability differential among MN types/sizes in ALS. Studying disease progression using SOD mice neuroscores is more accurate than using age, which could distort the statistical differences between SOD and WT PIC/POC data and the trends during disease progression.}, } @article {pmid38924023, year = {2024}, author = {Spoden, C and Wenzel, O and Erdmann, A and Neitzke, G and Hirschberg, I}, title = {Coping and end-of-life decision-making in ALS: A qualitative interview study.}, journal = {PloS one}, volume = {19}, number = {6}, pages = {e0306102}, pmid = {38924023}, issn = {1932-6203}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/psychology ; Male ; Female ; Middle Aged ; *Adaptation, Psychological ; *Decision Making ; *Terminal Care/psychology ; Aged ; *Qualitative Research ; Adult ; Germany ; Interviews as Topic ; }, abstract = {How do people with amyotrophic lateral sclerosis (PALS) deal with their diagnosis and engage in end-of-life decision-making? What informational or supportive needs do they have for counselling about life-sustaining treatment and end-of-life care? Which correlating conditions and influences relate to these needs and how do they connect to the wish to die or wish to live? We conducted a qualitative interview study with 13 people with ALS in Germany from March 2019 to April 2021. Data collection and analysis followed a grounded theory-based approach and revealed close relationships between coping, informational needs and the preparedness for decision-making. We identified the coping strategies 'avoid thinking about end-of-life' and its counterpart, 'planning ahead to be well-prepared,' and differentiated the latter into the patterns 'withdrawing from life and taking precautions against life-prolongation' and 'searching for a new meaning in life and preparing for life-sustaining treatment'. The approaches are based on individual perceptions, attitudes and motives and can be positively/negatively reinforced by healthcare professionals (HCP), family and other interpersonal networks, but also by disease progression and in reaction to health care services. Type and degree of needs concerning information and counselling differed according to coping strategies. These strategies may vary over time, resulting in different support needs. Our findings signify that deep insight is needed into PALS' coping processes to understand their decision-making about life-sustaining treatment. Healthcare professionals should be sensitive to illness experiences beyond medical aspects and foster coping as a biographical process to better support people with ALS.}, } @article {pmid38923692, year = {2024}, author = {Snyder, A and Ryan, VH and Hawrot, J and Lawton, S and Ramos, DM and Qi, YA and Johnson, KR and Reed, X and Johnson, NL and Kollasch, AW and Duffy, MF and VandeVrede, L and Cochran, JN and Miller, BL and Toro, C and Bielekova, B and Marks, DS and Yokoyama, JS and Kwan, JY and Cookson, MR and Ward, ME}, title = {An ANXA11 P93S variant dysregulates TDP-43 and causes corticobasal syndrome.}, journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association}, volume = {20}, number = {8}, pages = {5220-5235}, pmid = {38923692}, issn = {1552-5279}, support = {K01AG049152//NIH National Institute on Aging/ ; 75N95022C00031/DA/NIDA NIH HHS/United States ; K01 AG049152/AG/NIA NIH HHS/United States ; U54NS123985//NIH National Institute of Neurological Disorders and Stroke/ ; ZIAAG000534/AG/NIA NIH HHS/United States ; FI2 GM142475/GM/NIGMS NIH HHS/United States ; U54 NS123985/NS/NINDS NIH HHS/United States ; P30AG062422//NIH National Institute on Aging/ ; 1ZIAAG000539-01//NIH National Institute on Aging/ ; R00 AG068271/AG/NIA NIH HHS/United States ; //Global Brain Health Institute/ ; //NIH Undiagnosed Diseases Program, Undiagnosed Diseases Network/ ; P50 AG023501/AG/NIA NIH HHS/United States ; //National Institute of Allergy and Infectious Diseases/ ; R01 AG062588/AG/NIA NIH HHS/United States ; /ALZ/Alzheimer's Association/United States ; R00AG068271//NIH National Institute on Aging/ ; P01AG019724//NIH National Institute on Aging/ ; U19 AG079774/AG/NIA NIH HHS/United States ; R01AG057234//NIH National Institute on Aging/ ; FI2GM142475//NIH National Institute of General Medical Sciences/ ; P30 AG062422/AG/NIA NIH HHS/United States ; K23AG073514//NIH National Institute on Aging/ ; P01 AG019724/AG/NIA NIH HHS/United States ; 2016-A-005-SUP//Larry L. Hillblom Foundation/ ; //NIH Office of Intramural Training and Education/ ; R01 AG057234/AG/NIA NIH HHS/United States ; ZIA AG000534/ImNIH/Intramural NIH HHS/United States ; //Chan-Zuckerberg Initiative's Neurodegeneration Challenge Network/ ; ZIA AG000539/ImNIH/Intramural NIH HHS/United States ; //Rainwater Charitable Foundation/ ; //Bluefield Project to Cure Frontotemporal Dementia/ ; //French Foundation/ ; U19AG079774//NIH National Institute on Aging/ ; P50AG023501//NIH National Institute on Aging/ ; //Intramural Research Programs of the National Institute of Neurological Disorders and Stroke/ ; P01AG1972403//NIH National Institute on Aging/ ; //HudsonAlpha Foundation Memory and Mobility Fund/ ; R01AG062588//NIH National Institute on Aging/ ; K23 AG073514/AG/NIA NIH HHS/United States ; //Mary Oakley Foundation/ ; }, mesh = {Humans ; *DNA-Binding Proteins/genetics/metabolism ; *Annexins/genetics ; Male ; Mutation/genetics ; Female ; Amyotrophic Lateral Sclerosis/genetics/pathology ; Neurons/metabolism/pathology ; Frontotemporal Dementia/genetics/pathology ; Middle Aged ; Aged ; }, abstract = {INTRODUCTION: Variants of uncertain significance (VUS) surged with affordable genetic testing, posing challenges for determining pathogenicity. We examine the pathogenicity of a novel VUS P93S in Annexin A11 (ANXA11) - an amyotrophic lateral sclerosis/frontotemporal dementia-associated gene - in a corticobasal syndrome kindred. Established ANXA11 mutations cause ANXA11 aggregation, altered lysosomal-RNA granule co-trafficking, and transactive response DNA binding protein of 43 kDa (TDP-43) mis-localization.

METHODS: We described the clinical presentation and explored the phenotypic diversity of ANXA11 variants. P93S's effect on ANXA11 function and TDP-43 biology was characterized in induced pluripotent stem cell-derived neurons alongside multiomic neuronal and microglial profiling.

RESULTS: ANXA11 mutations were linked to corticobasal syndrome cases. P93S led to decreased lysosome colocalization, neuritic RNA, and nuclear TDP-43 with cryptic exon expression. Multiomic microglial signatures implicated immune dysregulation and interferon signaling pathways.

DISCUSSION: This study establishes ANXA11 P93S pathogenicity, broadens the phenotypic spectrum of ANXA11 mutations, underscores neuronal and microglial dysfunction in ANXA11 pathophysiology, and demonstrates the potential of cellular models to determine variant pathogenicity.

HIGHLIGHTS: ANXA11 P93S is a pathogenic variant. Corticobasal syndrome is part of the ANXA11 phenotypic spectrum. Hybridization chain reaction fluorescence in situ hybridization (HCR FISH) is a new tool for the detection of cryptic exons due to TDP-43-related loss of splicing regulation. Microglial ANXA11 and related immune pathways are important drivers of disease. Cellular models are powerful tools for adjudicating variants of uncertain significance.}, } @article {pmid38923364, year = {2024}, author = {Yang, XD and Gong, B and Chen, W and Chen, JJ and Qian, C and Lu, R and Min, Y and Jiang, T and Li, L and Yu, HQ}, title = {In Situ Quantitative Monitoring of Adsorption from Aqueous Phase by UV-vis Spectroscopy: Implication for Understanding of Heterogeneous Processes.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {11}, number = {32}, pages = {e2402732}, pmid = {38923364}, issn = {2198-3844}, support = {//Program for Changjiang Scholars and Innovative Research Team in University/ ; 51821006//National Natural Science Foundation of China/ ; 52027815//National Natural Science Foundation of China/ ; 52192684//National Natural Science Foundation of China/ ; 22276217//National Natural Science Foundation of China/ ; }, abstract = {The development of in situ techniques to quantitatively characterize the heterogeneous reactions is essential for understanding physicochemical processes in aqueous phase. In this work, a new approach coupling in situ UV-vis spectroscopy with a two-step algorithm strategy is developed to quantitatively monitor heterogeneous reactions in a compact closed-loop incorporation. The algorithm involves the inverse adding-doubling method for light scattering correction and the multivariate curve resolution-alternating least squares (MCR-ALS) method for spectral deconvolution. Innovatively, theoretical spectral simulations are employed to connect MCR-ALS solutions with chemical molecular structural evolution without prior information for reference spectra. As a model case study, the aqueous adsorption kinetics of bisphenol A onto polyamide microparticles are successfully quantified in a one-step UV-vis spectroscopic measurement. The practical applicability of this approach is confirmed by rapidly screening a superior adsorbent from commercial materials for antibiotic wastewater adsorption treatment. The demonstrated capabilities are expected to extend beyond monitoring adsorption systems to other heterogeneous reactions, significantly advancing UV-vis spectroscopic techniques toward practical integration into automated experimental platforms for probing aqueous chemical processes and beyond.}, } @article {pmid38923228, year = {2024}, author = {Koch, T and Fabian, R and Weinhold, L and Koch, FW and Barakat, S and Castro-Gomez, S and Grehl, T and Bernsen, S and Weydt, P}, title = {Cardiac troponin T as a serum biomarker of respiratory impairment in amyotrophic lateral sclerosis.}, journal = {Annals of clinical and translational neurology}, volume = {11}, number = {8}, pages = {2063-2072}, pmid = {38923228}, issn = {2328-9503}, support = {//Boris Canessa Foundation/ ; 21060//Alzheimer Forschung Initiative e.V/ ; 2021-1A-12//Hertie Network of Excellence in Clinical Neuroscience/ ; //BONFOR-Forschungskommission der Medizinischen Fakultät Bonn/ ; //Neuro-aCSis Bonn Neuroscience Clinician Scientist Program/ ; EXC2151-390873048//Deutsche Forschungsgemeinschaft/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/blood/diagnosis/physiopathology ; *Troponin T/blood ; Male ; Middle Aged ; Female ; *Biomarkers/blood ; Aged ; Retrospective Studies ; Vital Capacity/physiology ; Respiratory Insufficiency/blood/etiology ; Adult ; Neurofilament Proteins/blood ; }, abstract = {OBJECTIVE: Informative biomarkers are an urgent need in the management of amyotrophic lateral sclerosis. Serum cardiac troponin T is elevated in the majority of amyotrophic lateral sclerosis patients and increases with disease progression. We sought to establish the informative value of cardiac troponin T with regard to respiratory function, a major prognostic factor in amyotrophic lateral sclerosis.

METHODS: In this retrospective observation, we analyzed two independent hospital-based cohorts (d = discovery cohort; v = validation cohort) regarding serum cardiac troponin T (nd = 298; nv = 49), serum neurofilament light chain (nd = 117; nv = 17), and respiratory tests (nd = 93; nv = 49).

RESULTS: Serum cardiac troponin T, in contrast to serum neurofilament levels, was associated with the respiratory domain of the revised amyotrophic lateral sclerosis functional rating scale and with pulmonary function parameters, namely forced vital capacity % (r = -0.45, p = 0.001) and slow vital capacity % (r = -0.50, p = 0.001). Serum cardiac troponin T reliably discriminated benchmarks of slow vital capacity <80% (AUC 0.73, 95% CI 0.62-0.84) and <50% (AUC 0.80, 95% CI 0.68-0.93), forced vital capacity <80% (AUC 0.72, 95% CI 0.61-0.83) and <50% (AUC 0.79, 95% CI 0.67-0.91).

INTERPRETATION: Our findings position cardiac Troponin T as a valuable serum biomarker in amyotrophic lateral sclerosis, complementing neurofilaments and expanding the understanding of underlying physiological mechanisms. In clinical practice, serum cardiac troponin T can flag benchmarks of compromised respiratory function.}, } @article {pmid38922880, year = {2025}, author = {Goldschmidt-Clermont, PJ and Khan, A and Jimsheleishvili, G and Graham, P and Brooks, A and Silvera, R and Goldschmidt, AJP and Pearse, DD and Dietrich, WD and Levi, AD and Guest, JD}, title = {Treating amyotrophic lateral sclerosis with allogeneic Schwann cell-derived exosomal vesicles: a case report.}, journal = {Neural regeneration research}, volume = {20}, number = {4}, pages = {1207-1216}, pmid = {38922880}, issn = {1673-5374}, abstract = {Schwann cells are essential for the maintenance and function of motor neurons, axonal networks, and the neuromuscular junction. In amyotrophic lateral sclerosis, where motor neuron function is progressively lost, Schwann cell function may also be impaired. Recently, important signaling and potential trophic activities of Schwann cell-derived exosomal vesicles have been reported. This case report describes the treatment of a patient with advanced amyotrophic lateral sclerosis using serial intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles, marking, to our knowledge, the first instance of such treatment. An 81-year-old male patient presented with a 1.5-year history of rapidly progressive amyotrophic lateral sclerosis. After initial diagnosis, the patient underwent a combination of generic riluzole, sodium phenylbutyrate for the treatment of amyotrophic lateral sclerosis, and taurursodiol. The patient volunteered to participate in an FDA-approved single-patient expanded access treatment and received weekly intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles to potentially restore impaired Schwann cell and motor neuron function. We confirmed that cultured Schwann cells obtained from the amyotrophic lateral sclerosis patient via sural nerve biopsy appeared impaired (senescent) and that exposure of the patient's Schwann cells to allogeneic Schwann cell-derived exosomal vesicles, cultured expanded from a cadaver donor improved their growth capacity in vitro. After a period of observation lasting 10 weeks, during which amyotrophic lateral sclerosis Functional Rating Scale-Revised and pulmonary function were regularly monitored, the patient received weekly consecutive infusions of 1.54 × 10 12 (×2), and then consecutive infusions of 7.5 × 10 12 (×6) allogeneic Schwann cell-derived exosomal vesicles diluted in 40 mL of Dulbecco's phosphate-buffered saline. None of the infusions were associated with adverse events such as infusion reactions (allergic or otherwise) or changes in vital signs. Clinical lab serum neurofilament and cytokine levels measured prior to each infusion varied somewhat without a clear trend. A more sensitive in-house assay suggested possible inflammasome activation during the disease course. A trend for clinical stabilization was observed during the infusion period. Our study provides a novel approach to address impaired Schwann cells and possibly motor neuron function in patients with amyotrophic lateral sclerosis using allogeneic Schwann cell-derived exosomal vesicles. Initial findings suggest that this approach is safe.}, } @article {pmid38921286, year = {2024}, author = {Katz, L and Gur, A}, title = {Psychosocial Intervention for Family Caregivers of ALS Patients: A Systematic Review.}, journal = {Healthcare (Basel, Switzerland)}, volume = {12}, number = {12}, pages = {}, pmid = {38921286}, issn = {2227-9032}, abstract = {PROPOSAL: This systematic review aims to comprehensively examine all existing knowledge on psychosocial interventions for family caregivers for ALS patients. Also, the study will present the gaps in knowledge, recommendations for future research, and guidelines for psychosocial interventions that are focused and adapted to the needs of family caregivers of ALS patients.

MATERIALS AND METHODS: The systematic review was conducted according to the PRISMA guidelines and identified studies on psychosocial intervention for family caregivers of ALS patients, using five electronic databases: PsychNET, PubMed, EBSCO, PRIMO, and PROQUEST. Seven articles met the criteria and were included in the review. A thematic analysis was conducted to extract major themes.

RESULTS: Three major themes emerged from the data: (1) Personal benefits; (2) Interpersonal benefits; and (3) Charting challenges and pathways to improve psychosocial interventions.

CONCLUSIONS: Based on the findings, practical guidelines were formulated that focus on the group's composition, the facilitator's role, the contents, the relationships within the group, and the opportunities and limitations of online interventions.}, } @article {pmid38921029, year = {2024}, author = {Carata, E and Muci, M and Di Giulio, S and Di Giulio, T and Mariano, S and Panzarini, E}, title = {The Neuromuscular Disorder Mediated by Extracellular Vesicles in Amyotrophic Lateral Sclerosis.}, journal = {Current issues in molecular biology}, volume = {46}, number = {6}, pages = {5999-6017}, pmid = {38921029}, issn = {1467-3045}, abstract = {Amyotrophic lateral sclerosis (ALS) represents a neurodegenerative disorder characterized by the progressive loss of both upper and lower motor neurons, resulting in muscular atrophy and eventual paralysis. While much research has concentrated on investigating the impact of major mutations associated with ALS on motor neurons and central nervous system (CNS) cells, recent studies have unveiled that ALS pathogenesis extends beyond CNS imbalances, encompassing dysregulation in other tissues such as skeletal muscle. Evidence from animal models and patients supports this broader perspective. Skeletal muscle, once considered solely as an effector organ, is now recognized as possessing significant secretory activity capable of influencing motor neuron survival. However, the precise cellular and molecular mechanisms underlying the detrimental effects observed in muscle and its associated structures in ALS remain poorly understood. Additionally, emerging data suggest that extracellular vesicles (EVs) may play a role in the establishment and function of the neuromuscular junction (NMJ) under both physiological and pathological conditions and in wasting and regeneration of skeletal muscles, particularly in neurodegenerative diseases like ALS. This review aims to explore the key findings about skeletal muscle involvement in ALS, shedding light on the potential underlying mechanisms and contributions of EVs and their possible application for the design of biosensors.}, } @article {pmid38920997, year = {2024}, author = {Nowak, I and Paździor, M and Sarna, R and Madej, M}, title = {Molecular Mechanisms in the Design of Novel Targeted Therapies for Neurodegenerative Diseases.}, journal = {Current issues in molecular biology}, volume = {46}, number = {6}, pages = {5436-5453}, pmid = {38920997}, issn = {1467-3045}, abstract = {Neurodegenerative diseases are a diverse group of diseases characterized by a progressive loss of neurological function due to damage to nerve cells in the central nervous system. In recent years, there has been a worldwide increase in the expanding associated with increasing human life expectancy. Molecular mechanisms control many of the essential life processes of cells, such as replication, transcription, translation, protein synthesis and gene regulation. These are complex interactions that form the basis for understanding numerous processes in the organism and developing new diagnostic and therapeutic approaches. In the context of neurodegenerative diseases, molecular basis refers to changes at the molecular level that cause damage to or degeneration of nerve cells. These may include protein aggregates leading to pathological structures in brain cells, impaired protein transport in nerve cells, mitochondrial dysfunction, inflammatory processes or genetic mutations that impair nerve cell function. New medical therapies are based on these mechanisms and include gene therapies, reduction in inflammation and oxidative stress, and the use of miRNAs and regenerative medicine. The aim of this study was to bring together the current state of knowledge regarding selected neurodegenerative diseases, presenting the underlying molecular mechanisms involved, which could be potential targets for new forms of treatment.}, } @article {pmid38920691, year = {2024}, author = {Ilieva, MS}, title = {Non-Coding RNAs in Neurological and Neuropsychiatric Disorders: Unraveling the Hidden Players in Disease Pathogenesis.}, journal = {Cells}, volume = {13}, number = {12}, pages = {}, pmid = {38920691}, issn = {2073-4409}, mesh = {Humans ; *RNA, Untranslated/genetics/metabolism ; *Nervous System Diseases/genetics/metabolism ; *Mental Disorders/genetics/metabolism ; RNA, Circular/genetics/metabolism ; Animals ; RNA, Long Noncoding/genetics/metabolism ; Gene Expression Regulation ; MicroRNAs/genetics/metabolism ; }, abstract = {Neurological and neuropsychiatric disorders pose substantial challenges to public health, necessitating a comprehensive understanding of the molecular mechanisms underlying their pathogenesis. In recent years, the focus has shifted toward the intricate world of non-coding RNAs (ncRNAs), a class of RNA molecules that do not encode proteins but play pivotal roles in gene regulation and cellular processes. This review explores the emerging significance of ncRNAs in the context of neurological and neuropsychiatric disorders, shedding light on their diverse functions and regulatory mechanisms. The dysregulation of various ncRNAs, including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), has been implicated in the pathophysiology of conditions such as Alzheimer's disease, Parkinson's disease, schizophrenia, and mood disorders. This review delves into the specific roles these ncRNAs play in modulating key cellular processes, including synaptic plasticity, neuroinflammation, and apoptosis, providing a nuanced understanding of their impact on disease progression. Furthermore, it discusses the potential diagnostic and therapeutic implications of targeting ncRNAs in neurological and neuropsychiatric disorders. The identification of specific ncRNA signatures holds promise for the development of novel biomarkers for early disease detection, while the manipulation of ncRNA expression offers innovative therapeutic avenues. Challenges and future directions in the field are also considered, highlighting the need for continued research to unravel the complexities of ncRNA-mediated regulatory networks in the context of neurological and neuropsychiatric disorders. This review aims to provide a comprehensive overview of the current state of knowledge and stimulate further exploration into the fascinating realm of ncRNAs in the brain's intricate landscape.}, } @article {pmid38920626, year = {2024}, author = {Cihankaya, H and Bader, V and Winklhofer, KF and Vorgerd, M and Matschke, J and Stahlke, S and Theiss, C and Matschke, V}, title = {Elevated NLRP3 Inflammasome Activation Is Associated with Motor Neuron Degeneration in ALS.}, journal = {Cells}, volume = {13}, number = {12}, pages = {}, pmid = {38920626}, issn = {2073-4409}, support = {91753179//German Academic Exchange Service/ ; }, mesh = {Animals ; *Amyotrophic Lateral Sclerosis/metabolism/pathology ; *NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; *Motor Neurons/metabolism/pathology ; *Inflammasomes/metabolism ; Mice ; *MicroRNAs/metabolism/genetics ; Spinal Cord/pathology/metabolism ; Disease Models, Animal ; Nerve Degeneration/pathology/metabolism ; Microglia/metabolism/pathology ; Mice, Inbred C57BL ; Caspase 1/metabolism ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by motor neuron degeneration in the central nervous system. Recent research has increasingly linked the activation of nucleotide oligomerization domain-like receptor protein 3 (NLRP3) inflammasome to ALS pathogenesis. NLRP3 activation triggers Caspase 1 (CASP 1) auto-activation, leading to the cleavage of Gasdermin D (GSDMD) and pore formation on the cellular membrane. This process facilitates cytokine secretion and ultimately results in pyroptotic cell death, highlighting the complex interplay of inflammation and neurodegeneration in ALS. This study aimed to characterize the NLRP3 inflammasome components and their colocalization with cellular markers using the wobbler mouse as an ALS animal model. Firstly, we checked the levels of miR-223-3p because of its association with NLRP3 inflammasome activity. The wobbler mice showed an increased expression of miR-223-3p in the ventral horn, spinal cord, and cerebellum tissues. Next, increased levels of NLRP3, pro-CASP 1, cleaved CASP 1 (c-CASP 1), full-length GSDMD, and cleaved GDSMD revealed NLRP3 inflammasome activation in wobbler spinal cords, but not in the cerebellum. Furthermore, we investigated the colocalization of the aforementioned proteins with neurons, microglia, and astrocyte markers in the spinal cord tissue. Evidently, the wobbler mice displayed microgliosis, astrogliosis, and motor neuron degeneration in this tissue. Additionally, we showed the upregulation of protein levels and the colocalization of NLRP3, c-CASP1, and GSDMD in neurons, as well as in microglia and astrocytes. Overall, this study demonstrated the involvement of NLRP3 inflammasome activation and pyroptotic cell death in the spinal cord tissue of wobbler mice, which could further exacerbate the motor neuron degeneration and neuroinflammation in this ALS mouse model.}, } @article {pmid38918634, year = {2024}, author = {Zhang, N and Westerhaus, A and Wilson, M and Wang, E and Goff, L and Sockanathan, S}, title = {Physiological regulation of neuronal Wnt activity is essential for TDP-43 localization and function.}, journal = {The EMBO journal}, volume = {43}, number = {16}, pages = {3388-3413}, pmid = {38918634}, issn = {1460-2075}, support = {T32GM007445//HHS | National Institutes of Health (NIH)/ ; T32 GM007445/GM/NIGMS NIH HHS/United States ; F31AG072745//HHS | National Institutes of Health (NIH)/ ; R01 AG068043/AG/NIA NIH HHS/United States ; 5RO1AG068043//HHS | National Institutes of Health (NIH)/ ; F31 AG072745/AG/NIA NIH HHS/United States ; }, mesh = {Humans ; *DNA-Binding Proteins/metabolism/genetics ; Animals ; *Wnt Signaling Pathway ; *Neurons/metabolism ; Mice ; *Phosphoric Diester Hydrolases/metabolism/genetics ; Amyotrophic Lateral Sclerosis/metabolism/genetics/pathology ; Active Transport, Cell Nucleus ; Cell Nucleus/metabolism ; }, abstract = {Nuclear exclusion of the RNA- and DNA-binding protein TDP-43 can induce neurodegeneration in different diseases. Diverse processes have been implicated to influence TDP-43 mislocalization, including disrupted nucleocytoplasmic transport (NCT); however, the physiological pathways that normally ensure TDP-43 nuclear localization are unclear. The six-transmembrane enzyme glycerophosphodiester phosphodiesterase 2 (GDE2 or GDPD5) cleaves the glycosylphosphatidylinositol (GPI) anchor that tethers some proteins to the membrane. Here we show that GDE2 maintains TDP-43 nuclear localization by regulating the dynamics of canonical Wnt signaling. Ablation of GDE2 causes aberrantly sustained Wnt activation in adult neurons, which is sufficient to cause NCT deficits, nuclear pore abnormalities, and TDP-43 nuclear exclusion. Disruption of GDE2 coincides with TDP-43 abnormalities in postmortem tissue from patients with amyotrophic lateral sclerosis (ALS). Further, GDE2 deficits are evident in human neural cell models of ALS, which display erroneous Wnt activation that, when inhibited, increases mRNA levels of genes regulated by TDP-43. Our study identifies GDE2 as a critical physiological regulator of Wnt signaling in adult neurons and highlights Wnt pathway activation as an unappreciated mechanism contributing to nucleocytoplasmic transport and TDP-43 abnormalities in disease.}, } @article {pmid38918466, year = {2024}, author = {Bahram Sangani, N and Koetsier, J and Mélius, J and Kutmon, M and Ehrhart, F and Evelo, CT and Curfs, LMG and Reutelingsperger, CP and Eijssen, LMT}, title = {A novel insight into neurological disorders through HDAC6 protein-protein interactions.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {14666}, pmid = {38918466}, issn = {2045-2322}, mesh = {*Histone Deacetylase 6/metabolism/genetics ; Humans ; *Protein Interaction Maps ; Nervous System Diseases/metabolism/genetics ; Alzheimer Disease/metabolism/genetics ; Phosphorylation ; Acetylation ; Parkinson Disease/metabolism/genetics/pathology ; }, abstract = {Due to its involvement in physiological and pathological processes, histone deacetylase 6 (HDAC6) is considered a promising pharmaceutical target for several neurological manifestations. However, the exact regulatory role of HDAC6 in the central nervous system (CNS) is still not fully understood. Hence, using a semi-automated literature screening technique, we systematically collected HDAC6-protein interactions that are experimentally validated and reported in the CNS. The resulting HDAC6 network encompassed 115 HDAC6-protein interactions divided over five subnetworks: (de)acetylation, phosphorylation, protein complexes, regulatory, and aggresome-autophagy subnetworks. In addition, 132 indirect interactions identified through HDAC6 inhibition were collected and categorized. Finally, to display the application of our HDAC6 network, we mapped transcriptomics data of Alzheimer's disease, Parkinson's disease, and Amyotrophic Lateral Sclerosis on the network and highlighted that in the case of Alzheimer's disease, alterations predominantly affect the HDAC6 phosphorylation subnetwork, whereas differential expression within the deacetylation subnetwork is observed across all three neurological disorders. In conclusion, the HDAC6 network created in the present study is a novel and valuable resource for the understanding of the HDAC6 regulatory mechanisms, thereby providing a framework for the integration and interpretation of omics data from neurological disorders and pharmacodynamic assessments.}, } @article {pmid38918327, year = {2024}, author = {Sharma, V and Sharma, P and Singh, TG}, title = {Mechanistic insights on TLR-4 mediated inflammatory pathway in neurodegenerative diseases.}, journal = {Pharmacological reports : PR}, volume = {76}, number = {4}, pages = {679-692}, pmid = {38918327}, issn = {2299-5684}, mesh = {Humans ; *Toll-Like Receptor 4/metabolism ; *Neurodegenerative Diseases/metabolism/drug therapy ; Animals ; *Signal Transduction ; NF-kappa B/metabolism ; Inflammation/metabolism/drug therapy ; }, abstract = {Neurodegenerative diseases (NDDs) pose a significant issue in healthcare, needing a thorough knowledge of their complex molecular mechanisms. A diverse set of cell signaling mediators and their interactions play critical roles in neuroinflammation. The release of pro-inflammatory mediators in response to neural dysfunction is detrimental to normal cell survival. Moreover, the important role of nuclear factor-κB (NF-κB) in the central nervous system through Toll-like receptor (TLR) activation has been well established. Therefore, through a comprehensive review of current research and experimentation, this investigation elucidates the interactions between novel pharmacological agents (TLR-4/NF-κB inhibitors) and neurodegeneration encompassing Alzheimer's, Parkinson's, Huntington's disease, amyotrophic lateral sclerosis and stroke. Insights garnered from this exploration underscore the potential of TLR-4 as a therapeutic target. Through the revelation of these insights, our aim is to establish a foundation for the development of enhanced and focused therapeutic approaches in the continuous endeavor to combat neurodegeneration. This review thus serves as a roadmap, guiding future research endeavors toward innovative strategies for combatting the complex interplay between TLR-4 signaling and NDDs.}, } @article {pmid38917863, year = {2024}, author = {Chou, CZ and Everett, EA and McFarlin, J and Ramanathan, U}, title = {End-of-Life and Hospice Care in Neurologic Diseases.}, journal = {Seminars in neurology}, volume = {44}, number = {5}, pages = {523-533}, doi = {10.1055/s-0044-1787809}, pmid = {38917863}, issn = {1098-9021}, mesh = {Humans ; *Nervous System Diseases/therapy ; *Hospice Care ; *Terminal Care/methods ; Advance Care Planning ; }, abstract = {The care of a patient with neurologic disease at end-of-life requires expertise in addressing advance care planning, hospice, symptom management, and caregiver support. Neurologists caring for patients with advanced neurologic disease often identify changes in disease trajectory, functional status, or goals of care that prompt discussions of advance care planning and hospice. Patients nearing end-of-life may develop symptoms such as dyspnea, secretions, delirium, pain, and seizures. Neurologists may be the primary clinicians managing these symptoms, particularly in the hospitalized patient, though they may also lend their expertise to non-neurologists about expected disease trajectories and symptoms in advanced neurologic disease. This article aims to help neurologists guide patients and caregivers through the end-of-life process by focusing on general knowledge that can be applied across diseases as well as specific considerations in severe stroke and traumatic brain injury, amyotrophic lateral sclerosis, Parkinson's disease, and dementia.}, } @article {pmid38917432, year = {2024}, author = {Atkinson, RAK and Collins, JM and Sreedharan, J and King, AE and Fernandez-Martos, CM}, title = {Alterations to metabolic hormones in amyotrophic lateral sclerosis and frontotemporal dementia postmortem human tissue.}, journal = {Journal of neuropathology and experimental neurology}, volume = {83}, number = {11}, pages = {907-916}, pmid = {38917432}, issn = {1554-6578}, support = {//"la Caixa" Banking Foundation/ ; PR-HR18-000341b//Fundación Luzón/ ; //Victorian Brain Bank/ ; //The Florey, The Alfred, Victorian Institute of Forensic Medicine/ ; //Coroners Court of Victoria/ ; //Fundación Luzón/ ; //The Alfred, Victorian Institute of Forensic Medicine/ ; //Parkinson's Victoria/ ; //FightMND/ ; //Yulgilbar Foundation/ ; //Ian and Maria Cootes/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism/pathology/genetics ; Male ; Female ; Aged ; *Frontotemporal Dementia/metabolism/pathology/genetics ; Middle Aged ; *Neuropeptide Y/metabolism ; Receptors, Leptin/metabolism/genetics ; Receptor, Insulin/metabolism ; Aged, 80 and over ; Spinal Cord/metabolism/pathology ; RNA, Messenger/metabolism ; Motor Cortex/metabolism/pathology ; Antigens, CD ; }, abstract = {Metabolic changes are observed in patients with both amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Although regulation of metabolic processes in the CNS is predominantly carried out within the hypothalamus, extra-hypothalamic CNS areas contain metabolic hormone receptors, including those for leptin (LEPR), insulin (INSR), and neuropeptide Y (NPY), indicating that they may play a role in biological processes underlying pathogenic disease processes. The status of these hormones within regions vulnerable in ALS/FTD is not well described. This study sought to determine whether the expression of these hormones and their receptors is altered in pathology-rich regions in cases of human FTD (superior frontal gyrus and insular cortex) and ALS (primary motor cortex and lumbar spinal cord) with TDP-43 pathology compared to matched healthy controls. LEPR mRNA was increased within the superior frontal gyrus of FTD cases and within primary motor cortex and lumbar spinal cord of ALS cases; INSR mRNA was increased in superior frontal gyrus and insular cortex of FTD cases. NPY protein was decreased in primary motor cortex and lumbar spinal cord of ALS cases. Our results demonstrate that metabolic hormones undergo complex alterations in ALS and FTD and suggest that these hormones could play critical roles in the pathogenesis of these diseases.}, } @article {pmid38917317, year = {2024}, author = {LaBarbera, VA and Gill, E and Hill, NS and Sachs, G}, title = {The Louise Wilcox ALS Clinic at Rhode Island Hospital: 25th Anniversary (1999-2024).}, journal = {Rhode Island medical journal (2013)}, volume = {107}, number = {7}, pages = {51-53}, pmid = {38917317}, issn = {2327-2228}, mesh = {Rhode Island ; Humans ; *Amyotrophic Lateral Sclerosis/history ; Anniversaries and Special Events ; }, } @article {pmid38916909, year = {2024}, author = {Honda, H and Sadashima, S and Yoshimura, M and Sakurada, N and Koyama, S and Yagita, K and Hamasaki, H and Noguchi, H and Arahata, H and Sasagasako, N}, title = {Altered expression of human myxovirus resistance protein A in amyotrophic lateral sclerosis.}, journal = {Journal of neuropathology and experimental neurology}, volume = {83}, number = {9}, pages = {745-751}, doi = {10.1093/jnen/nlae052}, pmid = {38916909}, issn = {1554-6578}, mesh = {Humans ; *Myxovirus Resistance Proteins/genetics/metabolism ; *Amyotrophic Lateral Sclerosis/metabolism/pathology/genetics ; Female ; Male ; Middle Aged ; Aged ; *Spinal Cord/metabolism/pathology ; Adult ; Aged, 80 and over ; Anterior Horn Cells/pathology/metabolism ; DNA-Binding Proteins/metabolism/genetics ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder. The etiology of sporadic ALS (sALS) has not yet been clarified. An increasing body of evidence suggests the involvement of viral infections and interferons (IFNs). Human myxovirus resistance protein A (MxA) is an IFN-induced dynamin-like GTPase that acts as a potent antiviral factor. This study examined MxA expression in ALS patient spinal cords using immunohistochemistry. Thirty-two cases of sALS (pathologically proven ALS-TDP), 10 non-ALS, other neurological disease control cases were examined. In most ALS cases, MxA cytoplasmic condensates were observed in the remaining spinal anterior horn neurons. The ALS group had a significantly higher rate of MxA-highly expressing neurons than the non-ALS group. Colocalization of MxA cytoplasmic condensate and transactive response DNA-binding protein 43 kDa (TDP-43)-positive inclusions was rarely observed. Because MxA has antiviral activity induced by IFNs, our results suggest that IFNs are involved in the pathogenesis of ALS in spinal cord anterior horn neurons. Our study also suggests that monitoring viral infections and IFN activation in patients with ALS may be critically important.}, } @article {pmid38916676, year = {2024}, author = {Schaub, A and Erdmann, H and Scholz, V and Timmer, M and Cordts, I and Günther, R and Reilich, P and Abicht, A and Schöberl, F}, title = {Analysis and occurrence of biallelic pathogenic repeat expansions in RFC1 in a German cohort of patients with a main clinical phenotype of motor neuron disease.}, journal = {Journal of neurology}, volume = {271}, number = {9}, pages = {5804-5812}, pmid = {38916676}, issn = {1432-1459}, mesh = {Humans ; *Motor Neuron Disease/genetics ; *Phenotype ; *Replication Protein C/genetics ; Male ; Female ; Cohort Studies ; Germany ; *DNA Repeat Expansion ; Middle Aged ; Aged ; Adult ; }, abstract = {Biallelic pathogenic repeat expansions in RFC1 were recently identified as molecular origin of cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS) as well as of one of the most common causes of adult-onset ataxia. In the meantime, the phenotypic spectrum has expanded massively and now includes mimics of multiple system atrophy or parkinsonism. After identifying a patient with a clinical diagnosis of amyotrophic lateral sclerosis (ALS) as a carrier of biallelic pathogenic repeat expansions in RFC1, we studied a cohort of 106 additional patients with a clinical main phenotype of motor neuron disease (MND) to analyze whether such repeat expansions are more common in MND patients. Indeed, two additional MND patients (one also with ALS and one with primary lateral sclerosis/PLS) have been identified as carrier of biallelic pathogenic repeat expansions in RFC1 in the absence of another genetic alteration explaining the phenotype, suggesting motor neuron disease as another extreme phenotype of RFC1 spectrum disorder. Therefore, MND might belong to the expanding phenotypic spectrum of pathogenic RFC1 repeat expansions, particularly in those MND patients with additional features such as sensory and/or autonomic neuropathy, vestibular deficits, or cerebellar signs. By systematically analyzing the RFC1 repeat array using Oxford nanopore technology long-read sequencing, our study highlights the high intra- and interallelic heterogeneity of this locus and allows the identification of the novel repeat motif 'ACAAG'.}, } @article {pmid38915796, year = {2024}, author = {Thonhoff, JR and Beers, DR and Zhao, W and Faridar, A and Thome, A and Wen, S and Zhang, A and Wang, J and Appel, SH}, title = {A phase 1 proof-of-concept study evaluating safety, tolerability, and biological marker responses with combination therapy of CTLA4-Ig and interleukin-2 in amyotrophic lateral sclerosis.}, journal = {Frontiers in neurology}, volume = {15}, number = {}, pages = {1415106}, pmid = {38915796}, issn = {1664-2295}, abstract = {OBJECTIVE: To determine whether a combination therapy with abatacept (CTLA4-Ig) and interleukin-2 (IL-2) is safe and suppresses markers of oxidative stress, inflammation, and degeneration in ALS.

METHODS: In this open-label study, four participants with ALS received subcutaneous injections of low dose IL-2 (1 × 10[6] IU/injection/day) for 5 consecutive days every 2 weeks and one subcutaneous injection of CTLA4-Ig (125 mg/mL/injection) every 2 weeks coinciding with the first IL-2 injection of each treatment cycle. Participants received a total of 24 treatment cycles during the first 48 weeks in this 56-week study. They were closely monitored for treatment-emergent adverse events (TEAEs) and disease progression with the ALSFRS-R. Phenotypic changes within T cell populations and serum biological markers of oxidative stress [4-hydroxynonenal (4-HNE) and oxidized-LDL (ox-LDL)], inflammation (IL-18), and structural neuronal degeneration [neurofilament light chain (Nf-L)] were assessed longitudinally.

RESULTS: CTLA4-Ig/IL-2 therapy was safe and well-tolerated in all four participants over the 56-week study. During the first 24 weeks, the average rate of change in the ALSFRS-R was +0.04 points/month. Over the 48-week treatment period, the average rate of change was -0.13 points/month with one participant improving by 0.9 points/month while the other three participants experienced an average decrease of -0.47 points/month, which is slower than the average - 1.1 points/month prior to initiation of therapy. Treg suppressive function and numbers increased during treatment. Responses in the biological markers during the first 16 weeks coincided with minimal clinical progression. Mean levels of 4-HNE decreased by 30%, ox-LDL decreased by 19%, IL-18 decreased by 23%, and Nf-L remained the same, on average, in all four participants. Oxidized-LDL levels decreased in all four participants, 4-HNE and IL-18 levels decreased in three out of four participants, and Nf-L decreased in two out of four participants.

CONCLUSION: The combination therapy of CTLA4-Ig and IL-2 in ALS is safe and well-tolerated with promising results of clinical efficacy and suppression of biomarkers of oxidative stress, neuroinflammation and neuronal degeneration. In this open-label study, the efficacy as measured by the ALSFRS-R and corresponding biomarkers suggests the therapeutic potential of this treatment and warrants further study in a phase 2 double-blind, placebo-controlled trial.

CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT06307301.}, } @article {pmid38915767, year = {2024}, author = {Ambrosini, A and Dalla Bella, E and Ravasi, M and Melazzini, M and Lauria, G}, title = {New clinical insight in amyotrophic lateral sclerosis and innovative clinical development from the non-profit repurposing trial of the old drug guanabenz.}, journal = {Frontiers in medicine}, volume = {11}, number = {}, pages = {1407912}, pmid = {38915767}, issn = {2296-858X}, abstract = {Drug repurposing is considered a valid approach to accelerate therapeutic solutions for rare diseases. However, it is not as widely applied as it could be, due to several barriers that discourage both industry and academic institutions from pursuing this path. Herein we present the case of an academic multicentre study that considered the repurposing of the old drug guanabenz as a therapeutic strategy in amyotrophic lateral sclerosis. The difficulties encountered are discussed as an example of the barriers that academics involved in this type of study may face. Although further development of the drug for this target population was hampered for several reasons, the study was successful in many ways. Firstly, because the hypothesis tested was confirmed in a sub-population, leading to alternative innovative solutions that are now under clinical investigation. In addition, the study was informative and provided new insights into the disease, which are now giving new impetus to laboratory research. The message from this example is that even a repurposing study with an old product has the potential to generate innovation and interest from industry partners, provided it is based on a sound rationale, the study design is adequate to ensure meaningful results, and the investigators keep the full clinical development picture in mind.}, } @article {pmid38915526, year = {2024}, author = {Mackness, BC and Morgan, BR and Deveau, LM and Kathuria, SV and Zitzewitz, JA and Massi, F}, title = {A hydrophobic core stabilizes the residual structure in the RRM2 intermediate state of the ALS-linked protein TDP-43.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2024.06.12.598648}, pmid = {38915526}, issn = {2692-8205}, abstract = {Folding intermediates mediate both protein folding and the misfolding and aggregation observed in human diseases, including amyotrophic lateral sclerosis (ALS), and are prime targets for therapeutic interventions. In this study, we identified the core nucleus of structure for a folding intermediate in the second RNA recognition motif (RRM2) of the ALS-linked RNA-binding protein, TDP-43, using a combination of experimental and computational approaches. Urea equilibrium unfolding studies revealed that the RRM2 intermediate state consists of collapsed residual secondary structure localized to the N-terminal half of RRM2, while the C-terminus is largely disordered. Steered molecular dynamics simulations and mutagenesis studies yielded key stabilizing hydrophobic contacts that, when mutated to alanine, severely disrupt the overall fold of RRM2. In combination, these findings suggest a role for this RRM intermediate in normal TDP-43 function as well as serving as a template for misfolding and aggregation through the low stability and non-native secondary structure.}, } @article {pmid38914810, year = {2024}, author = {Manchia, M and Paribello, P and Pinna, M and Steardo, L and Carpiniello, B and Pinna, F and Pisanu, C and Squassina, A and Hajek, T}, title = {Lithium and its effects: does dose matter?.}, journal = {International journal of bipolar disorders}, volume = {12}, number = {1}, pages = {23}, pmid = {38914810}, issn = {2194-7511}, abstract = {BACKGROUND: Decades of clinical research have demonstrated the efficacy of lithium in treating acute episodes (both manic and depressive), as well as in preventing recurrences of bipolar disorder (BD). Specific to lithium is its antisuicidal effect, which appears to extend beyond its mood-stabilizing properties. Lithium's clinical effectiveness is, to some extent, counterbalanced by its safety and tolerability profile. Indeed, monitoring of lithium levels is required by its narrow therapeutic index. There is consensus that adequate serum levels should be above 0.6 mEq/L to achieve clinical effectiveness. However, few data support the choice of this threshold, and increasing evidence suggests that lithium might have clinical and molecular effects at much lower concentrations.

CONTENT: This narrative review is aimed at: (1) reviewing and critically interpreting the clinical evidence supporting the use of the 0.6 mEq/L threshold, (2) reporting a narrative synthesis of the evidence supporting the notion that lithium might be effective in much lower doses. Among these are epidemiological studies of lithium in water, evidence on the antisuicidal, anti-aggressive, and neuroprotective effects, including efficacy in preventing cognitive impairment progression, Alzheimer's disease (AD), and amyotrophic lateral sclerosis (ALS), of lithium; and (3) revieweing biological data supporting clinically viable uses of lithium at low levels with the delineation of a mechanistic hypothesis surrounding its purported mechanism of action. The study selection was based on the authors' preference, reflecting the varied and extensive expertise on the review subject, further enriched with an extensive pearl-growing strategy for relevant reviews and book sections.

CONCLUSIONS: Clinical and molecular effects of lithium are numerous, and its effects also appear to have a certain degree of specificity related to the dose administered. In sum, the clinical effects of lithium are maximal for mood stabilisation at concentrations higher than 0.6 mEq/l. However, lower levels may be sufficient for preventing depressive recurrences in older populations of patients, and microdoses could be effective in decreasing suicide risk, especially in patients with BD. Conversely, lithium's ability to counteract cognitive decline appears to be exerted at subtherapeutic doses, possibly corresponding to its molecular neuroprotective effects. Indeed, lithium may reduce inflammation and induce neuroprotection even at doses several folds lower than those commonly used in clinical settings. Nevertheless, findings surrounding its purported mechanism of action are missing, and more research is needed to investigate the molecular targets of low-dose lithium adequately.}, } @article {pmid38914784, year = {2024}, author = {Sang, A and Zhuo, S and Bochanis, A and Manautou, JE and Bahal, R and Zhong, XB and Rasmussen, TP}, title = {Mechanisms of Action of the US Food and Drug Administration-Approved Antisense Oligonucleotide Drugs.}, journal = {BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy}, volume = {38}, number = {4}, pages = {511-526}, pmid = {38914784}, issn = {1179-190X}, support = {R01 HL147028/HL/NHLBI NIH HHS/United States ; R35 GM140862/GM/NIGMS NIH HHS/United States ; R35GM140862/GM/NIGMS NIH HHS/United States ; R01HL147028/HL/NHLBI NIH HHS/United States ; }, mesh = {Humans ; *Oligonucleotides, Antisense/therapeutic use/pharmacology ; United States ; *United States Food and Drug Administration ; *Drug Approval ; RNA, Messenger/genetics/metabolism ; Animals ; RNA Splicing/drug effects ; }, abstract = {Antisense oligonucleotides (ASOs) are single stranded nucleic acids that target RNA. The US Food and Drug Administration has approved ASOs for several diseases. ASOs utilize three principal modes of action (MOA). The first MOA is initiated by base-pairing between the ASO and its target mRNA, followed by RNase H-dependent mRNA degradation. The second MOA is triggered by ASOs that occlude splice acceptor sites in pre-mRNAs leading to skipping of a mutation-bearing exon. The third MOA involves ASOs that sterically hinder mRNA function, often inhibiting translation. ASOs contain a variety of modifications to the sugar-phosphate backbone and bases that stabilize the ASO or render them resistant to RNase activity. RNase H-dependent ASOs include inotersen and eplontersen (for hereditary transthyretin amyloidosis), fomiversen (for opportunistic cytomegalovirus infection), mipomersen (for familial hypercholesterolemia), and tofersen [for amyotrophic lateral sclerosis (ALS)]. Splice modulating ASOs include nursinersen (for spinal muscular atrophy) and eteplirsen, golodirsen, viltolarsen, and casimersen (all for the treatment of Duchenne muscular dystrophy). In addition, a designer ASO, milasen, was used to treat a single individual afflicted with Batten disease. Since ASO design relies principally upon knowledge of mRNA sequence, the bench to bedside pipeline for ASOs is expedient compared with protein-directed drugs. [Graphical abstract available.].}, } @article {pmid38914219, year = {2024}, author = {Asahina, R and Takahashi, M and Takano, H and Yao, R and Abe, M and Goshima, Y and Ohshima, T}, title = {The role of CRMP4 in LPS-induced neuroinflammation.}, journal = {Brain research}, volume = {1841}, number = {}, pages = {149094}, doi = {10.1016/j.brainres.2024.149094}, pmid = {38914219}, issn = {1872-6240}, mesh = {Animals ; *Lipopolysaccharides/pharmacology ; *Microglia/metabolism/drug effects ; *Mice, Knockout ; *Nerve Tissue Proteins/metabolism/genetics ; Mice ; *Neuroinflammatory Diseases/metabolism/chemically induced ; Inflammation/metabolism/chemically induced ; Interleukin-10/metabolism ; Substantia Nigra/metabolism/drug effects ; Mice, Inbred C57BL ; Corpus Striatum/metabolism/drug effects ; Male ; Microfilament Proteins/metabolism ; Arginase/metabolism ; }, abstract = {Neuroinflammation has been gaining attention as one of the potential causes of neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis in recent years. The suppression of excessive proinflammatory responses is expected to be a target for the treatment and prevention of neurodegenerative diseases. Collapsin response mediator protein 4 (CRMP4) is involved in cytoskeleton-associated axonal guidance in the developing brain. Recently, the involvement of CRMP4 in several pathological conditions, including inflammation induced by lipopolysaccharide (LPS), a widely used inflammatory molecule, has been reported. However, the role of CRMP4 in LPS-induced inflammation in vivo remains largely unknown. In this study, we generated microglia-specific CRMP4 knockout mice for the first time and examined the role of CRMP4 in an LPS-induced brain inflammation model. We found that microglia after LPS injection in substantia nigra was significantly reduced in Crmp4[-/-] mice compared to Crmp4[+/+]mice. The increased expression of IL-10 in striatum samples was downregulated in Crmp4[-/-] mice. A significant reduction in Iba1 expression was also observed in microglia-specific Crmp4 knockout mice compared with that in control mice. In contrast, the expression of IL-10 did not change in these mice, whereas arginase 1 (Arg1) expression was significantly suppressed. These results demonstrate the involvement of CRMP4 in LPS-induced inflammation in vivo, that CRMP4 suppresses microglial proliferation in a cell-autonomous manner.}, } @article {pmid38914173, year = {2024}, author = {Tortarolo, M and Re Cecconi, AD and Camporeale, L and Margotta, C and Nardo, G and Pasetto, L and Bonetto, V and Galbiati, M and Crippa, V and Poletti, A and Piccirillo, R and Bendotti, C}, title = {Sunitinib-mediated inhibition of STAT3 in skeletal muscle and spinal cord does not affect the disease in a mouse model of ALS.}, journal = {Neurobiology of disease}, volume = {199}, number = {}, pages = {106576}, doi = {10.1016/j.nbd.2024.106576}, pmid = {38914173}, issn = {1095-953X}, mesh = {Animals ; *Amyotrophic Lateral Sclerosis/metabolism/drug therapy/pathology ; *Sunitinib/pharmacology ; *Muscle, Skeletal/drug effects/metabolism/pathology ; *STAT3 Transcription Factor/metabolism/antagonists & inhibitors ; *Mice, Transgenic ; *Indoles/pharmacology ; Mice ; *Disease Models, Animal ; *Spinal Cord/metabolism/drug effects/pathology ; *Mice, Inbred C57BL ; *Pyrroles/pharmacology ; Superoxide Dismutase/metabolism/genetics ; Muscular Atrophy/metabolism/pathology ; Motor Neurons/drug effects/metabolism/pathology ; Disease Progression ; }, abstract = {Variability in disease onset and progression is a hallmark of amyotrophic lateral sclerosis (ALS), both in sporadic and genetic forms. Recently, we found that SOD1-G93A transgenic mice expressing the same amount of mutant SOD1 but with different genetic backgrounds, C57BL/6JOlaHsd and 129S2/SvHsd, show slow and rapid muscle wasting and disease progression, respectively. Here, we investigated the different molecular mechanisms underlying muscle atrophy. Although both strains showed similar denervation-induced degradation of muscle proteins, only the rapidly progressing mice exhibited early and sustained STAT3 activation that preceded atrophy in gastrocnemius muscle. We therefore investigated the therapeutic potential of sunitinib, a tyrosine kinase inhibitor known to inhibit STAT3 and prevent cancer-induced muscle wasting. Although sunitinib treatment reduced STAT3 activation in the gastrocnemius muscle and lumbar spinal cord, it did not preserve spinal motor neurons, improve neuromuscular impairment, muscle atrophy and disease progression in the rapidly progressing SOD1-G93A mice. Thus, the effect of sunitinib is not equally positive in different diseases associated with muscle wasting. Moreover, given the complex role of STAT3 in the peripheral and central compartments of the neuromuscular system, the present study suggests that its broad inhibition may lead to opposing effects, ultimately preventing a potential positive therapeutic action in ALS.}, } @article {pmid38913386, year = {2024}, author = {Shamaskin-Garroway, AM and Shamaskin, J}, title = {Slowing Down-A Family's Experience With ALS.}, journal = {JAMA neurology}, volume = {81}, number = {9}, pages = {907-908}, doi = {10.1001/jamaneurol.2024.1922}, pmid = {38913386}, issn = {2168-6157}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis ; Family/psychology ; Male ; Female ; Middle Aged ; }, } @article {pmid38911266, year = {2024}, author = {Huang, X and Lee, S and Chen, K and Kawaguchi, R and Wiskow, O and Ghosh, S and Frost, D and Perrault, L and Pandey, R and Klim, JR and Boivin, B and Hermawan, C and Livak, KJ and Geschwind, DH and Wainger, BJ and Eggan, KC and Bean, BP and Woolf, CJ}, title = {Downregulation of the silent potassium channel Kv8.1 increases motor neuron vulnerability in amyotrophic lateral sclerosis.}, journal = {Brain communications}, volume = {6}, number = {3}, pages = {fcae202}, pmid = {38911266}, issn = {2632-1297}, support = {P50 HD105351/HD/NICHD NIH HHS/United States ; R35 NS127216/NS/NINDS NIH HHS/United States ; }, abstract = {While voltage-gated potassium channels have critical roles in controlling neuronal excitability, they also have non-ion-conducting functions. Kv8.1, encoded by the KCNV1 gene, is a 'silent' ion channel subunit whose biological role is complex since Kv8.1 subunits do not form functional homotetramers but assemble with Kv2 to modify its ion channel properties. We profiled changes in ion channel expression in amyotrophic lateral sclerosis patient-derived motor neurons carrying a superoxide dismutase 1(A4V) mutation to identify what drives their hyperexcitability. A major change identified was a substantial reduction of KCNV1/Kv8.1 expression, which was also observed in patient-derived neurons with C9orf72 expansion. We then studied the effect of reducing KCNV1/Kv8.1 expression in healthy motor neurons and found it did not change neuronal firing but increased vulnerability to cell death. A transcriptomic analysis revealed dysregulated metabolism and lipid/protein transport pathways in KCNV1/Kv8.1-deficient motor neurons. The increased neuronal vulnerability produced by the loss of KCNV1/Kv8.1 was rescued by knocking down Kv2.2, suggesting a potential Kv2.2-dependent downstream mechanism in cell death. Our study reveals, therefore, unsuspected and distinct roles of Kv8.1 and Kv2.2 in amyotrophic lateral sclerosis-related neurodegeneration.}, } @article {pmid38909659, year = {2024}, author = {Issa, NT and Bunick, CG}, title = {In response to Reynolds et al's "guidelines of care for the management of acne vulgaris".}, journal = {Journal of the American Academy of Dermatology}, volume = {91}, number = {4}, pages = {e113-e114}, doi = {10.1016/j.jaad.2024.05.091}, pmid = {38909659}, issn = {1097-6787}, mesh = {Humans ; *Acne Vulgaris/therapy/diagnosis/drug therapy ; *Practice Guidelines as Topic ; }, } @article {pmid38909349, year = {2024}, author = {Ketabforoush, A and Faghihi, F and Azedi, F and Ariaei, A and Habibi, MA and Khalili, M and Ashtiani, BH and Joghataei, MT and Arnold, WD}, title = {Sodium Phenylbutyrate and Tauroursodeoxycholic Acid: A Story of Hope Turned to Disappointment in Amyotrophic Lateral Sclerosis Treatment.}, journal = {Clinical drug investigation}, volume = {44}, number = {7}, pages = {495-512}, pmid = {38909349}, issn = {1179-1918}, mesh = {Humans ; *Taurochenodeoxycholic Acid/pharmacology/therapeutic use ; *Amyotrophic Lateral Sclerosis/drug therapy/physiopathology ; *Phenylbutyrates/therapeutic use/pharmacology ; Neuroprotective Agents/therapeutic use/pharmacology ; }, abstract = {The absence of a definitive cure for amyotrophic lateral sclerosis (ALS) emphasizes the crucial need to explore new and improved treatment approaches for this fatal, progressive, and disabling neurodegenerative disorder. As at the end of 2023, five treatments - riluzole, edaravone, dextromethorphan hydrobromide + quinidine sulfate (DHQ), tofersen, and sodium phenylbutyrate-tauroursodeoxycholic acid (PB-TUDCA) - were FDA approved for the treatment of patients with ALS. Among them PB-TUDCA has been shown to impact DNA processing impairments, mitochondria dysfunction, endoplasmic reticulum stress, oxidative stress, and pathologic folded protein agglomeration defects, which have been associated with ALS pathophysiology. The Phase 2 CENTAUR trial demonstrated significant impact of PB-TUDCA on the ALS Functional Rating Scale-Revised (ALSFRS-R) risk of death, hospitalization, and the need for tracheostomy or permanent assisted ventilation in patients with ALS based on post hoc analyses. More recently, contrasting with the CENTAUR trial results, results from the Phase 3 PHOENIX trial (NCT05021536) showed no change in ALSFRS-R total score at 48 weeks. Consequently, the sponsor company initiated the process with the US FDA and Health Canada to voluntarily withdraw the marketing authorizations for PB-TUDCA. In the present article, we review ALS pathophysiology, with a focus on PB-TUDCA's proposed mechanisms of action and recent clinical trial results and discuss the implications of conflicting trial data for ALS and other neurological disorders.}, } @article {pmid38909342, year = {2024}, author = {Réginault, T and Wibart, P and Mathis, S and Le Masson, G and Pillet, O and Grassion, L}, title = {Factors associated with survival after early at-home NIV initiation in ALS patients.}, journal = {Journal of neurology}, volume = {271}, number = {8}, pages = {5590-5597}, pmid = {38909342}, issn = {1432-1459}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy/mortality/physiopathology ; Male ; Female ; *Noninvasive Ventilation ; Middle Aged ; Retrospective Studies ; Aged ; Respiratory Insufficiency/therapy/mortality/etiology ; Home Care Services ; }, abstract = {BACKGROUND: The initiation of early non-invasive ventilation (NIV) often involves a careful balance between tolerance and effectiveness. In amyotrophic lateral sclerosis (ALS) patients, the establishment of a strategy, including the decision to focus on adhering to a cut-off, setting specific targets, or correcting all events, is crucial.

OBJECTIVE: To identify factors at 1 month after early at-home NIV initiation that are associated with improved survival in ALS patients. We explored the impacts of adherence (ADH), quality of treatment, and NIV parameters at 1 month after early at-home NIV initiation on patient survival.

METHODS: We conducted a retrospective study of 184 ALS patients at the Bordeaux ALS Centre for whom NIV was initiated between September 2017 and June 2021, and we collected data for a minimum period of 2 years after the last patient included. The primary outcome was the risk of death according to baseline characteristics of our population and the NIV parameters and monitoring during the early NIV initiation period. The secondary outcomes were association with NIV ADH during the early NIV initiation period on prognosis, and NIV ADH cut-off for good versus poor prognosis.

RESULTS: Among the 178 ALS patients analysed, we found that quality of NIV treatment and device settings did not significantly influence prognosis. However, low ADH was significantly associated with a higher risk of death. The use of NIV for > 5 h/day during the early NIV initiation period was linked to a decreased risk of death [hazard ratio = 0.4; 95% confidence interval: 0.27-0.9].

CONCLUSION: The use of NIV for > 5 h/day during the early NIV initiation period was associated with increased survival.}, } @article {pmid38909069, year = {2024}, author = {Ngo, TD and Kieu, HD and Nguyen, MH and Nguyen, TH and Can, VM and Nguyen, BH and Le, TH}, title = {An EEG & eye-tracking dataset of ALS patients & healthy people during eye-tracking-based spelling system usage.}, journal = {Scientific data}, volume = {11}, number = {1}, pages = {664}, pmid = {38909069}, issn = {2052-4463}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology ; *Brain-Computer Interfaces ; *Electroencephalography ; *Eye-Tracking Technology ; }, abstract = {This research presents a dataset consisting of electroencephalogram and eye tracking recordings obtained from six patients with amyotrophic lateral sclerosis (ALS) in a locked-in state and one hundred seventy healthy individuals. The ALS patients exhibited varying degrees of disease progression, ranging from partial mobility and weakened speech to complete paralysis and loss of speech. Despite these physical impairments, the ALS patients retained good eye function, which allowed them to use a virtual keyboard for communication. Data from ALS patients was recorded multiple times at their homes, while data from healthy individuals was recorded once in a laboratory setting. For each data recording, the experimental design involved nine recording sessions per participant, each corresponding to a common human action or demand. This dataset can serve as a valuable benchmark for several applications, such as improving spelling systems with brain-computer interfaces, investigating motor imagination, exploring motor cortex function, monitoring motor impairment progress in patients undergoing rehabilitation, and studying the effects of ALS on cognitive and motor processes.}, } @article {pmid38908354, year = {2024}, author = {Kim, K and Choi, D and Shim, H and Lee, CA}, title = {Effects of gamification in advanced life support training for clinical nurses: A cluster randomized controlled trial.}, journal = {Nurse education today}, volume = {140}, number = {}, pages = {106263}, doi = {10.1016/j.nedt.2024.106263}, pmid = {38908354}, issn = {1532-2793}, mesh = {Humans ; Female ; Adult ; Male ; *COVID-19/nursing ; Cardiopulmonary Resuscitation/education ; Clinical Competence/standards ; Advanced Cardiac Life Support/education ; Games, Experimental ; }, abstract = {BACKGROUND: Cardiopulmonary resuscitation training is a mandatory competency, especially for healthcare professionals. However, the spread of COVID-19 caused a sharp decline in the number of participants on advanced life support training, thereby accelerating the diversification of educational methods. Gamification is an increasingly popular method of diversifying instruction, but its effectiveness remains controversial.

AIM: To evaluate the effectiveness of gamification learning in advanced life support training.

DESIGN: A cluster randomized controlled trial.

SETTING: A single advanced life support training center.

PARTICIPANTS: Clinical nurses who are currently practicing in a hospital.

METHODS: A part of the existing advanced life support course was gamified using Kahoot! platform. Conventional learning and gamified learning were each conducted 11 times, and the level of knowledge after training was assessed. The assessment questions were categorized into advanced life support algorithms, teamwork, and cardiac arrest rhythms.

RESULTS: A total of 267 were enrolled in the study, and 148 and 139 learners were assigned to CL and GL, respectively. There was no difference in post-training knowledge related to teamwork, and cardiac arrest rhythms between the conventional learning and gamified learning groups, but knowledge related to the advanced life support algorithm was low in the gamified learning group.

CONCLUSIONS: Even if the learners are the same, advanced life support gamification training can lead to negative outcomes depending on the simplicity or goal of the training content. To improve the effectiveness of the training, various methods of gamification training should be applied depending on the goal and content of the training.}, } @article {pmid38908196, year = {2024}, author = {Donders, Z and Skorupska, IJ and Willems, E and Mussen, F and Broeckhoven, JV and Carlier, A and Schepers, M and Vanmierlo, T}, title = {Beyond PDE4 inhibition: A comprehensive review on downstream cAMP signaling in the central nervous system.}, journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie}, volume = {177}, number = {}, pages = {117009}, doi = {10.1016/j.biopha.2024.117009}, pmid = {38908196}, issn = {1950-6007}, mesh = {Humans ; *Cyclic AMP/metabolism ; *Phosphodiesterase 4 Inhibitors/pharmacology ; Animals ; *Central Nervous System/drug effects/metabolism ; *Signal Transduction/drug effects ; *Central Nervous System Diseases/drug therapy/metabolism/enzymology ; *Cyclic Nucleotide Phosphodiesterases, Type 4/metabolism ; }, abstract = {Cyclic adenosine monophosphate (cAMP) is a key second messenger that regulates signal transduction pathways pivotal for numerous biological functions. Intracellular cAMP levels are spatiotemporally regulated by their hydrolyzing enzymes called phosphodiesterases (PDEs). It has been shown that increased cAMP levels in the central nervous system (CNS) promote neuroplasticity, neurotransmission, neuronal survival, and myelination while suppressing neuroinflammation. Thus, elevating cAMP levels through PDE inhibition provides a therapeutic approach for multiple CNS disorders, including multiple sclerosis, stroke, spinal cord injury, amyotrophic lateral sclerosis, traumatic brain injury, and Alzheimer's disease. In particular, inhibition of the cAMP-specific PDE4 subfamily is widely studied because of its high expression in the CNS. So far, the clinical translation of full PDE4 inhibitors has been hampered because of dose-limiting side effects. Hence, focusing on signaling cascades downstream activated upon PDE4 inhibition presents a promising strategy, offering novel and pharmacologically safe targets for treating CNS disorders. Yet, the underlying downstream signaling pathways activated upon PDE(4) inhibition remain partially elusive. This review provides a comprehensive overview of the existing knowledge regarding downstream mediators of cAMP signaling induced by PDE4 inhibition or cAMP stimulators. Furthermore, we highlight existing gaps and future perspectives that may incentivize additional downstream research concerning PDE(4) inhibition, thereby providing novel therapeutic approaches for CNS disorders.}, } @article {pmid38908137, year = {2024}, author = {Cain, CN and Synovec, RE}, title = {Enhancing gas chromatography-mass spectrometry resolution and pure analyte discovery using intra-chromatogram elution profile matching.}, journal = {Talanta}, volume = {278}, number = {}, pages = {126453}, doi = {10.1016/j.talanta.2024.126453}, pmid = {38908137}, issn = {1873-3573}, abstract = {Chemometric decomposition methods like multivariate curve resolution-alternating least squares (MCR-ALS) are often employed in gas chromatography-mass spectrometry (GC-MS) to improve analyte identification and quantitation. However, these methods can perform poorly for analytes with a low chromatographic resolution (Rs) and a high degree of spectral contamination from noise and background interferences. Thus, we propose a novel computational algorithm, termed mzCompare, to improve analyte identification and quantitation when coupled to MCR-ALS. The mzCompare method utilizes an underlying requirement that the retention time and peak shape between mass channels (m/z) of the same analyte should be similar. By discovering the selective m/z for a given analyte in a chromatogram, a pure elution profile can be generated and used as an equality constraint in MCR-ALS. The performance of the mzCompare methodology is demonstrated with both experimental and simulated chromatograms. Experimentally, unresolved analytes with a Rs as low as 0.05 could be confidently identified with mzCompare assisted MCR-ALS. Furthermore, application of the mzCompare algorithm to a complex aerospace fuel resulted in the discovery of 335 analytes, a 44 % increase compared to conventional peak detection methods. GC-MS simulations of target-interferent analyte pairs demonstrated that the performance of MCR-ALS deteriorated below a Rs of ∼0.25. However, mzCompare assisted MCR-ALS showed excellent identification and acceptable quantitative accuracy at a Rs of ∼0.02. These results show that the mzCompare algorithm can help analysts overcome modeling ambiguities resulting from the chemometric multiplex disadvantage.}, } @article {pmid38907861, year = {2024}, author = {Yang, T and Wei, Q and Pang, D and Cheng, Y and Huang, J and Lin, J and Xiao, Y and Jiang, Q and Wang, S and Li, C and Shang, H}, title = {Clinical and genetic characteristics of ALS patients with variants in genes regulating DNA methylation.}, journal = {Journal of neurology}, volume = {271}, number = {8}, pages = {5556-5566}, pmid = {38907861}, issn = {1432-1459}, support = {82371430//National Natural Science Foundation of China/ ; 2022ZDZX0023//Sichuan Science and Technology Program/ ; YCXJ-JZ-2022-007//Beijing E-town Coorperation & Development Foundation/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics ; *DNA Methylation ; Female ; Male ; Middle Aged ; Aged ; China ; Genetic Predisposition to Disease/genetics ; DNA-Binding Proteins/genetics ; Cohort Studies ; Adult ; Dioxygenases ; Genetic Variation ; }, abstract = {BACKGROUND: Aberrant DNA methylation alterations are implicated in amyotrophic lateral sclerosis (ALS). Nevertheless, the influence of genetic variants in genes regulating DNA methylation on ALS patients is not well understood. Therefore, we aim to provide a comprehensive variant profile of genes related to DNA methylation (DNMT1, DNMT3A, DNMT3B, DNMT3L) and demethylation (TET1, TET2, TET3, TDG) and to investigate the association of these variants with ALS.

METHODS: Variants were screened in a cohort of 2240 ALS patients from Southwest China, using controls from the Genome Aggregation Database (n = 9976) and the China Metabolic Analytics Project (n = 10,588). The over-representation of rare variants and their association with ALS risk were evaluated using Fisher's exact test with Bonferroni correction at both allele and gene levels. Kaplan-Meier analysis and Cox regression analysis were employed to explore the relationship between variants and survival.

RESULTS: A total of 210 variants meeting the criteria were identified. Gene-based burden analysis identified a significant increase in ALS risk associated with rare variants in the TET2 gene (OR = 1.95, 95% CI = 1.29-2.88, P = 0.001). Survival analysis demonstrated that patients carrying variants in demethylation-related genes had a higher risk of death compared to those with methylation-related gene variants (HR = 1.29, 95% CI = 1.03-1.86, P = 0.039).

CONCLUSIONS: This study provides a genetic variant profile of genes involved in DNA methylation and demethylation regulation, along with the clinical characteristics of ALS patients carrying these variants. The findings offer genetic evidence implicating disrupted DNA methylation dynamics in ALS.}, } @article {pmid38907103, year = {2024}, author = {Limone, F and Mordes, DA and Couto, A and Joseph, BJ and Mitchell, JM and Therrien, M and Ghosh, SD and Meyer, D and Zhang, Y and Goldman, M and Bortolin, L and Cobos, I and Stevens, B and McCarroll, SA and Kadiu, I and Burberry, A and Pietiläinen, O and Eggan, K}, title = {Single-nucleus sequencing reveals enriched expression of genetic risk factors in extratelencephalic neurons sensitive to degeneration in ALS.}, journal = {Nature aging}, volume = {4}, number = {7}, pages = {984-997}, pmid = {38907103}, issn = {2662-8465}, support = {K08 NS104270/NS/NINDS NIH HHS/United States ; P50 AG005134/AG/NIA NIH HHS/United States ; P50 HD105351/HD/NICHD NIH HHS/United States ; }, mesh = {*Amyotrophic Lateral Sclerosis/genetics/pathology/metabolism ; Humans ; *Neurons/metabolism/pathology ; Risk Factors ; Microglia/metabolism/pathology ; Cell Nucleus/metabolism/genetics ; Oligodendroglia/metabolism/pathology ; Male ; Single-Cell Analysis ; Sequence Analysis, RNA ; Female ; Middle Aged ; Nerve Degeneration/genetics/pathology/metabolism ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by a progressive loss of motor function linked to degenerating extratelencephalic neurons/Betz cells (ETNs). The reasons why these neurons are selectively affected remain unclear. Here, to understand the unique molecular properties that may sensitize ETNs to ALS, we performed RNA sequencing of 79,169 single nuclei from cortices of patients and controls. In both patients and unaffected individuals, we found significantly higher expression of ALS risk genes in THY1[+] ETNs, regardless of diagnosis. In patients, this was accompanied by the induction of genes involved in protein homeostasis and stress responses that were significantly induced in a wide collection of ETNs. Examination of oligodendroglial and microglial nuclei revealed patient-specific downregulation of myelinating genes in oligodendrocytes and upregulation of an endolysosomal reactive state in microglia. Our findings suggest that selective vulnerability of extratelencephalic neurons is partly connected to their intrinsic molecular properties sensitizing them to genetics and mechanisms of degeneration.}, } @article {pmid38906677, year = {2024}, author = {Au, WH and Miller-Fleming, L and Sanchez-Martinez, A and Lee, JA and Twyning, MJ and Prag, HA and Raik, L and Allen, SP and Shaw, PJ and Ferraiuolo, L and Mortiboys, H and Whitworth, AJ}, title = {Activation of the Keap1/Nrf2 pathway suppresses mitochondrial dysfunction, oxidative stress, and motor phenotypes in C9orf72 ALS/FTD models.}, journal = {Life science alliance}, volume = {7}, number = {9}, pages = {}, pmid = {38906677}, issn = {2575-1077}, mesh = {*Amyotrophic Lateral Sclerosis/metabolism/genetics ; *Oxidative Stress ; *NF-E2-Related Factor 2/metabolism/genetics ; *C9orf72 Protein/genetics/metabolism ; *Mitochondria/metabolism ; Animals ; *Disease Models, Animal ; *Kelch-Like ECH-Associated Protein 1/metabolism/genetics ; Humans ; *Signal Transduction ; *Frontotemporal Dementia/genetics/metabolism ; *Phenotype ; Drosophila Proteins/metabolism/genetics ; Reactive Oxygen Species/metabolism ; Mitophagy/genetics ; Dimethyl Fumarate/pharmacology ; Male ; }, abstract = {Mitochondrial dysfunction is a common feature of C9orf72 amyotrophic lateral sclerosis/frontotemporal dementia (ALS/FTD); however, it remains unclear whether this is a cause or consequence of the pathogenic process. Analysing multiple aspects of mitochondrial biology across several Drosophila models of C9orf72-ALS/FTD, we found morphology, oxidative stress, and mitophagy are commonly affected, which correlated with progressive loss of locomotor performance. Notably, only genetic manipulations that reversed the oxidative stress levels were also able to rescue C9orf72 locomotor deficits, supporting a causative link between mitochondrial dysfunction, oxidative stress, and behavioural phenotypes. Targeting the key antioxidant Keap1/Nrf2 pathway, we found that genetic reduction of Keap1 or pharmacological inhibition by dimethyl fumarate significantly rescued the C9orf72-related oxidative stress and motor deficits. Finally, mitochondrial ROS levels were also elevated in C9orf72 patient-derived iNeurons and were effectively suppressed by dimethyl fumarate treatment. These results indicate that mitochondrial oxidative stress is an important mechanistic contributor to C9orf72 pathogenesis, affecting multiple aspects of mitochondrial function and turnover. Targeting the Keap1/Nrf2 signalling pathway to combat oxidative stress represents a therapeutic strategy for C9orf72-related ALS/FTD.}, } @article {pmid38906263, year = {2024}, author = {Veenstra, J and Ozog, D}, title = {Response to Barbieri, "Response to Veenstra et al's 'benzoyl peroxide use in acne therapy: Evaluating the association with acute myeloid leukemia risk'".}, journal = {Journal of the American Academy of Dermatology}, volume = {91}, number = {4}, pages = {e111-e112}, doi = {10.1016/j.jaad.2024.06.036}, pmid = {38906263}, issn = {1097-6787}, mesh = {Humans ; *Acne Vulgaris/drug therapy ; *Leukemia, Myeloid, Acute/drug therapy/chemically induced ; *Benzoyl Peroxide/therapeutic use/adverse effects ; Dermatologic Agents/adverse effects/therapeutic use ; }, } @article {pmid38906259, year = {2024}, author = {Barbieri, JS}, title = {Response to Veenstra et al's "Benzoyl peroxide use in acne therapy: Evaluating the association with acute myeloid leukemia risk".}, journal = {Journal of the American Academy of Dermatology}, volume = {91}, number = {4}, pages = {e109-e110}, doi = {10.1016/j.jaad.2024.05.090}, pmid = {38906259}, issn = {1097-6787}, mesh = {Humans ; *Acne Vulgaris/drug therapy ; *Leukemia, Myeloid, Acute/drug therapy/chemically induced ; *Benzoyl Peroxide/therapeutic use/adverse effects ; Dermatologic Agents/adverse effects/therapeutic use ; }, } @article {pmid38905535, year = {2024}, author = {}, title = {Addendum: Relyvrio withdrawn.}, journal = {The Medical letter on drugs and therapeutics}, volume = {66}, number = {1704}, pages = {96}, doi = {10.58347/tml.2024.1704e}, pmid = {38905535}, issn = {1523-2859}, mesh = {Humans ; Phenylbutyrates ; }, } @article {pmid38905382, year = {2024}, author = {Jing, Z and Qi, X and Teng, J}, title = {Dietary factors and risk for amyotrophic lateral sclerosis: A two sample mendelian randomization study.}, journal = {Medicine}, volume = {103}, number = {25}, pages = {e38473}, pmid = {38905382}, issn = {1536-5964}, mesh = {*Mendelian Randomization Analysis/methods ; *Amyotrophic Lateral Sclerosis/genetics/epidemiology/etiology ; Humans ; *Diet ; Risk Factors ; Fruit ; Genome-Wide Association Study ; Vegetables ; Coffee/adverse effects ; Meat/adverse effects ; }, abstract = {Correlations between dietary factors and amyotrophic lateral sclerosis (ALS) have been found in previous observational studies. However, no further studies have used Mendelian randomization to further explore the causal relationship between dietary factors and ALS. Clarifying these relationships is a crucial part of developing nutritional recommendations for ALS prevention. The exposure and outcome datasets employed in this study were extracted from the IEU Open GWAS project (https://gwas.mrcieu.ac.uk/). The exposure datasets involved in our Mendelian analyses consisted of meat intake (processed meat intake, poultry intake, beef intake, pork intake, non-oily fish intake, and oily fish intake), staple foods intake (bread intake and cereal intake), vegetable intake (cooked vegetable intake, salad/raw vegetable intake), fruit intake (fresh fruit intake and dried fruit intake), and beverage intake (coffee intake and tea intake). The weighted median, MR-Egger, Inverse Variance Weighted, Simple mode and Weighted mode methods were all utilized. And we applied Inverse Variance Weighted method as the main judgement criterion for Mendelian randomization analysis. Heterogeneity and pleiotropy analyses were conducted to confirm the validity of the outcomes. Genetically predicted that oily fish intake (OR: 0.7648; 95% CI: 0.5905-0.9904; P = .0420), coffee intake (OR: 0.7385; 95% CI: 0.5660-0.9637; P = .0256), and fresh fruit intake (OR: 0.6165; 95% CI: 0.4007-0.9487; P = .0278) were causally associated with a decreased risk of ALS. Negative results (P > .05) were received for all other dietary factors. This study found that oily fish intake, coffee intake and fresh fruit intake reduced the risk of developing ALS. Additionally, other factors were not associated with ALS.}, } @article {pmid38905379, year = {2024}, author = {Park, BK and Oh, SI and Kang, M and Seok, HY and Park, JM and Kim, S and Kim, HI and Kim, JA and Park, JS}, title = {Reliability and Validity of the Korean version of the Center for Neurologic Study Bulbar Function Scale (K-CNS-BFS): An observational study.}, journal = {Medicine}, volume = {103}, number = {25}, pages = {e38216}, pmid = {38905379}, issn = {1536-5964}, mesh = {Humans ; Male ; Female ; Republic of Korea ; Middle Aged ; Reproducibility of Results ; *Amyotrophic Lateral Sclerosis/physiopathology/complications/diagnosis ; Aged ; *Severity of Illness Index ; Adult ; }, abstract = {Bulbar dysfunction in amyotrophic lateral sclerosis (ALS) significantly affects daily life, leading to weight loss and reduced survival. Methods for evaluating bulbar dysfunction, including videofluoroscopic swallowing studies and the bulbar component of the ALS Functional Rating Scale-Revised (ALSFRS-R), have been employed; however, Korean-specific tools are lacking. The Center for Neurologic Study Bulbar Function Scale (CNS-BFS) comprehensively evaluates bulbar symptoms. This study aimed to develop and validate the Korean version of the CNS-BFS (K-CNS-BFS) to assess bulbar dysfunction in Korean patients with ALS. Twenty-seven patients with ALS were recruited from a tertiary hospital in South Korea based on revised El Escorial criteria. Demographic, clinical, and measurement data were collected. The K-CNS-BFS was evaluated for reliability and validity. Reliability assessment revealed strong internal consistency (Cronbach alpha) for the K-CNS-BFS subscales and total score. Test-retest reliability showed significant correlation. Content validity index was excellent, and convergent validity demonstrated significant correlations between the K-CNS-BFS and relevant measures. Discriminant validity was observed between the K-CNS-BFS and motor/respiratory subscores of the ALSFRS-R. Construct validity demonstrated significant correlations between the K-CNS-BFS subscales and total score. This is the first study to investigate the reliability and validity of the Korean version of the CNS-BFS, which showed consistent and reliable scores that correlated with tests for bulbar or general dysfunction. The K-CNS-BFS effectively measured bulbar dysfunction similar to the original CNS-BFS. The K-CNS-BFS is a reliable and valid tool for assessing bulbar dysfunction in patients with ALS in South Korea.}, } @article {pmid38904901, year = {2024}, author = {Aiello, EN and Torre, S and Solca, F and Curti, B and De Luca, G and Gendarini, C and Cocuzza, A and Colombo, E and Maranzano, A and Verde, F and Morelli, C and Messina, S and Doretti, A and Silani, V and Ticozzi, N and Poletti, B}, title = {Ecological validity of performance-based cognitive screeners in amyotrophic lateral sclerosis: preliminary evidence.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {45}, number = {11}, pages = {5319-5325}, pmid = {38904901}, issn = {1590-3478}, support = {Ministero della Salute//Ministero della Salute/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/psychology ; Male ; Female ; Middle Aged ; *Caregivers/psychology ; Aged ; *Neuropsychological Tests/standards ; Reproducibility of Results ; Cognition Disorders/diagnosis/etiology ; Adult ; }, abstract = {BACKGROUND: This study aimed at preliminarily assessing, in a cohort of non-demented amyotrophic lateral sclerosis (ALS) patients, the ecological validity, and more specifically the veridicality, of the Edinburgh Cognitive and Behavioural ALS Screen (ECAS) and the ALS Cognitive Behavioral Screen (ALS-CBS™), by relating their scores to caregiver-report ratings of cognitive changes.

METHODS: N = 147 patient-caregiver dyads were recruited. Patients were administered the ECAS and ALS-CBS™, whilst caregiver the Caregiver Behavioral Questionnaire (CBQ) and Beaumont Behavioural Inventory (BBI). An Ecological Cognitive Functioning Index (ECFI) was derived from those items of the CBQ and BBI that tap on executive and language changes. Ecological validity was assessed via both correlational and predictive analyses net of caregiver-rated behavioural changes (as assessed by the ECAS-Carer Interview).

RESULTS: The ECFI was associated with the total scores on both the ECAS (p = .014) and ALS-CBS™ (p = .017). When looking at ECAS and ALS-CBS™ subscales, those assessing verbal fluency were selectively associated with the ECFI. The ECFI was higher in patients performing defectively on the ECAS (p = .004) and on the ALS-CBS™ (p = .027).

DISCUSSION: This study suggests that both the ECAS and the ALS-CBS™ represent a valid estimate of non-demented ALS patients' cognitive status in the real world, also highlighting the clinical relevance of cognitive changes reported by caregivers.}, } @article {pmid38904729, year = {2024}, author = {Portes E Silva, KR and Nogueira, EM and Jesus Mendes, AL and Pena, ALB and Simões E Silva, AC}, title = {The potential role of renin angiotensin system in acute leukemia: a narrative review.}, journal = {Molecular biology reports}, volume = {51}, number = {1}, pages = {775}, pmid = {38904729}, issn = {1573-4978}, support = {304496/2023-5//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; }, mesh = {Humans ; *Renin-Angiotensin System/physiology ; *Precursor Cell Lymphoblastic Leukemia-Lymphoma/metabolism/pathology ; *Angiotensin II/metabolism ; Leukemia, Myeloid, Acute/metabolism/pathology ; Signal Transduction ; Angiotensin I/metabolism ; Neovascularization, Pathologic/metabolism ; Animals ; Peptide Fragments/metabolism ; }, abstract = {Acute leukemias (ALs) are the most common cancers in pediatric population. There are two types of ALs: acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). Some studies suggest that the Renin Angiotensin System (RAS) has a role in ALs. RAS signaling modulates, directly and indirectly, cellular activity in different cancers, affecting tumor cells and angiogenesis. Our review aimed to summarize the role of RAS in ALs and to explore future perspectives for the treatment of these hematological malignancies by modulating RAS molecules. The database including Pubmed, Scopus, Cochrane Library, and Scielo were searched to find articles about RAS molecules in ALL and in pediatric patients. The search terms were "RAS", "Acute Leukemia", "ALL", "Angiotensin-(1-7)", "Pediatric", "Cancer", "Angiotensin II", "AML". In the bone marrow, RAS has been found to play a key role in blood cell formation, affecting several processes including apoptosis, cell proliferation, mobilization, intracellular signaling, angiogenesis, fibrosis, and inflammation. Local tissue RAS modulates tumor growth and metastasis through autocrine and paracrine actions. RAS mainly acts via two molecules, Angiotensin II (Ang II) and Angiotensin (1-7) [Ang-(1-7)]. While Ang II promotes tumor cell growth and stimulates angiogenesis, Ang-(1-7) inhibits the proliferation of neoplastic cells and the angiogenesis, suggesting a potential therapeutic role of this molecule in ALL. The interaction between ALs and RAS reveals a complex network of molecules that can affect the hematopoiesis and the development of hematological cancers. Understanding these interactions could pave the way for innovative therapeutic approaches targeting RAS components.}, } @article {pmid38903602, year = {2024}, author = {Al-Kuraishy, HM and Jabir, MS and Sulaiman, GM and Mohammed, HA and Al-Gareeb, AI and Albuhadily, AK and Jawad, SF and Swelum, AA and Abomughaid, MM}, title = {The role of statins in amyotrophic lateral sclerosis: protective or not?.}, journal = {Frontiers in neuroscience}, volume = {18}, number = {}, pages = {1422912}, pmid = {38903602}, issn = {1662-4548}, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease of motor neurons characterized by muscle weakness, muscle twitching, and muscle wasting. ALS is regarded as the third-most frequent neurodegenerative disease, subsequent to Alzheimer's disease (AD) and Parkinson's disease (PD). The World Health Organization (WHO) in 2007 declared that prolonged use of statins may induce development of ALS-like syndrome and may increase ALS risk. Subsequently, different studies have implicated statins in the pathogenesis of ALS. In contrast, results from preclinical and clinical studies highlighted the protective role of statins against ALS neuropathology. Recently, meta-analyses and systematic reviews illustrated no association between long-term use of statins and ALS risk. These findings highlighted controversial points regarding the effects of statins on ALS pathogenesis and risk. The neuroprotective effects of statins against the development and progression of ALS may be mediated by regulating dyslipidemia and inflammatory changes. However, the mechanism for induction of ALS neuropathology by statins may be related to the dysregulation of liver X receptor signaling (LXR) signaling in the motor neurons and reduction of cholesterol, which has a neuroprotective effect against ALS neuropathology. Nevertheless, the exact role of statins on the pathogenesis of ALS was not fully elucidated. Therefore, this narrative review aims to discuss the role of statins in ALS neuropathology.}, } @article {pmid38903475, year = {2024}, author = {Dash, D and Teplansky, K and Ferrari, P and Babajani-Feremi, A and Calley, CS and Heitzman, D and Austin, SG and Wang, J}, title = {Automatic detection of ALS from single-trial MEG signals during speech tasks: a pilot study.}, journal = {Frontiers in psychology}, volume = {15}, number = {}, pages = {1114811}, pmid = {38903475}, issn = {1664-1078}, abstract = {Amyotrophic lateral sclerosis (ALS) is an idiopathic, fatal, and fast-progressive neurodegenerative disease characterized by the degeneration of motor neurons. ALS patients often experience an initial misdiagnosis or a diagnostic delay due to the current unavailability of an efficient biomarker. Since impaired speech is typical in ALS, we hypothesized that functional differences between healthy and ALS participants during speech tasks can be explained by cortical pattern changes, thereby leading to the identification of a neural biomarker for ALS. In this pilot study, we collected magnetoencephalography (MEG) recordings from three early-diagnosed patients with ALS and three healthy controls during imagined (covert) and overt speech tasks. First, we computed sensor correlations, which showed greater correlations for speakers with ALS than healthy controls. Second, we compared the power of the MEG signals in canonical bands between the two groups, which showed greater dissimilarity in the beta band for ALS participants. Third, we assessed differences in functional connectivity, which showed greater beta band connectivity for ALS than healthy controls. Finally, we performed single-trial classification, which resulted in highest performance with beta band features (∼ 98%). These findings were consistent across trials, phrases, and participants for both imagined and overt speech tasks. Our preliminary results indicate that speech-evoked beta oscillations could be a potential neural biomarker for diagnosing ALS. To our knowledge, this is the first demonstration of the detection of ALS from single-trial neural signals.}, } @article {pmid38903116, year = {2024}, author = {Matera, AG and Steiner, RE and Mills, CA and Herring, LE and Garcia, EL}, title = {Chaperoning the chaperones: Proteomic analysis of the SMN complex reveals conserved and etiologic connections to the proteostasis network.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {38903116}, issn = {2692-8205}, support = {P30 CA016086/CA/NCI NIH HHS/United States ; R35 GM136435/GM/NIGMS NIH HHS/United States ; }, abstract = {Molecular chaperones and co-chaperones are highly conserved cellular components that perform variety of duties related to the proper three-dimensional folding of the proteome. The web of factors that carries out this essential task is called the proteostasis network (PN). Ribonucleoproteins (RNPs) represent an underexplored area in terms of the connections they make with the PN. The Survival Motor Neuron (SMN) complex is an RNP assembly chaperone and serves as a paradigm for studying how specific small nuclear (sn)RNAs are identified and paired with their client substrate proteins. SMN protein is the eponymous component of a large complex required for the biogenesis of uridine-rich small nuclear ribonucleoproteins (U-snRNPs) and localizes to distinct membraneless organelles in both the nucleus and cytoplasm of animal cells. SMN forms the oligomeric core of this complex, and missense mutations in its YG box self-interaction domain are known to cause Spinal Muscular Atrophy (SMA). The basic framework for understanding how snRNAs are assembled into U-snRNPs is known, the pathways and mechanisms used by cells to regulate their biogenesis are poorly understood. Given the importance of these processes to normal development as well as neurodegenerative disease, we set out to identify and characterize novel SMN binding partners. Here, we carried out affinity purification mass spectrometry (AP-MS) of SMN using stable fly lines exclusively expressing either wildtype or SMA-causing missense alleles. Bioinformatic analyses of the pulldown data, along with comparisons to proximity labeling studies carried out in human cells, revealed conserved connections to at least two other major chaperone systems including heat shock folding chaperones (HSPs) and histone/nucleosome assembly chaperones. Notably, we found that heat shock cognate protein Hsc70-4 and other HspA family members preferentially interacted with SMA-causing alleles of SMN. Hsc70-4 is particularly interesting because its mRNA is aberrantly sequestered by a mutant form of TDP-43 in mouse and Drosophila ALS (Amyotrophic Lateral Sclerosis) disease models. Most important, a missense allele of Hsc70-4 (HspA8 in mammals) was recently identified as a bypass suppressor of the SMA phenotype in mice. Collectively, these findings suggest that chaperone-related dysfunction lies at the etiological root of both ALS and SMA.}, } @article {pmid38902980, year = {2024}, author = {Dratch, L and Kinnamon, DD and Harrington, EA and Goldman, J and Fong, JC and Jones, T and Uhlmann, WR and Roggenbuck, J}, title = {Response to "assessment of risk of ALS conferred by the GGGGCC hexanucleotide expansion in C9orf72 among first-degree relatives of patients with ALS carrying the repeat expansion".}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {25}, number = {7-8}, pages = {797-799}, doi = {10.1080/21678421.2024.2362854}, pmid = {38902980}, issn = {2167-9223}, } @article {pmid38902734, year = {2024}, author = {Hu, Y and Hruscha, A and Pan, C and Schifferer, M and Schmidt, MK and Nuscher, B and Giera, M and Kostidis, S and Burhan, Ö and van Bebber, F and Edbauer, D and Arzberger, T and Haass, C and Schmid, B}, title = {Mis-localization of endogenous TDP-43 leads to ALS-like early-stage metabolic dysfunction and progressive motor deficits.}, journal = {Molecular neurodegeneration}, volume = {19}, number = {1}, pages = {50}, pmid = {38902734}, issn = {1750-1326}, mesh = {Animals ; *Zebrafish ; *Amyotrophic Lateral Sclerosis/metabolism/pathology/genetics ; *DNA-Binding Proteins/metabolism/genetics ; *Disease Models, Animal ; *Motor Neurons/metabolism/pathology ; *Zebrafish Proteins/metabolism/genetics ; Animals, Genetically Modified ; Neuromuscular Junction/metabolism/pathology ; }, abstract = {BACKGROUND: The key pathological signature of ALS/ FTLD is the mis-localization of endogenous TDP-43 from the nucleus to the cytoplasm. However, TDP-43 gain of function in the cytoplasm is still poorly understood since TDP-43 animal models recapitulating mis-localization of endogenous TDP-43 from the nucleus to the cytoplasm are missing.

METHODS: CRISPR/Cas9 technology was used to generate a zebrafish line (called CytoTDP), that mis-locates endogenous TDP-43 from the nucleus to the cytoplasm. Phenotypic characterization of motor neurons and the neuromuscular junction was performed by immunostaining, microglia were immunohistochemically localized by whole-mount tissue clearing and muscle ultrastructure was analyzed by scanning electron microscopy. Behavior was investigated by video tracking and quantitative analysis of swimming parameters. RNA sequencing was used to identify mis-regulated pathways with validation by molecular analysis.

RESULTS: CytoTDP fish have early larval phenotypes resembling clinical features of ALS such as progressive motor defects, neurodegeneration and muscle atrophy. Taking advantage of zebrafish's embryonic development that solely relys on yolk usage until 5 days post fertilization, we demonstrated that microglia proliferation and activation in the hypothalamus is independent from food intake. By comparing CytoTDP to a previously generated TDP-43 knockout line, transcriptomic analyses revealed that mis-localization of endogenous TDP-43, rather than TDP-43 nuclear loss of function, leads to early onset metabolic dysfunction.

CONCLUSIONS: The new TDP-43 model mimics the ALS/FTLD hallmark of progressive motor dysfunction. Our results suggest that functional deficits of the hypothalamus, the metabolic regulatory center, might be the primary cause of weight loss in ALS patients. Cytoplasmic gain of function of endogenous TDP-43 leads to metabolic dysfunction in vivo that are reminiscent of early ALS clinical non-motor metabolic alterations. Thus, the CytoTDP zebrafish model offers a unique opportunity to identify mis-regulated targets for therapeutic intervention early in disease progression.}, } @article {pmid38902629, year = {2024}, author = {Takemoto, Y and Ito, D and Komori, S and Kishimoto, Y and Yamada, S and Hashizume, A and Katsuno, M and Nakatochi, M}, title = {Comparing preprocessing strategies for 3D-Gene microarray data of extracellular vesicle-derived miRNAs.}, journal = {BMC bioinformatics}, volume = {25}, number = {1}, pages = {221}, pmid = {38902629}, issn = {1471-2105}, support = {JP21wm0425013//Japan Agency for Medical Research and Development/ ; 23H00420//Japan Society for the Promotion of Science/ ; 16H06277//Japan Society for the Promotion of Science/ ; }, mesh = {*Extracellular Vesicles/metabolism/genetics ; *MicroRNAs/genetics/metabolism ; Humans ; *Oligonucleotide Array Sequence Analysis/methods ; Amyotrophic Lateral Sclerosis/genetics/metabolism ; Gene Expression Profiling/methods ; }, abstract = {BACKGROUND: Extracellular vesicle-derived (EV)-miRNAs have potential to serve as biomarkers for the diagnosis of various diseases. miRNA microarrays are widely used to quantify circulating EV-miRNA levels, and the preprocessing of miRNA microarray data is critical for analytical accuracy and reliability. Thus, although microarray data have been used in various studies, the effects of preprocessing have not been studied for Toray's 3D-Gene chip, a widely used measurement method. We aimed to evaluate batch effect, missing value imputation accuracy, and the influence of preprocessing on measured values in 18 different preprocessing pipelines for EV-miRNA microarray data from two cohorts with amyotrophic lateral sclerosis using 3D-Gene technology.

RESULTS: Eighteen different pipelines with different types and orders of missing value completion and normalization were used to preprocess the 3D-Gene microarray EV-miRNA data. Notable results were suppressed in the batch effects in all pipelines using the batch effect correction method ComBat. Furthermore, pipelines utilizing missForest for missing value imputation showed high agreement with measured values. In contrast, imputation using constant values for missing data exhibited low agreement.

CONCLUSIONS: This study highlights the importance of selecting the appropriate preprocessing strategy for EV-miRNA microarray data when using 3D-Gene technology. These findings emphasize the importance of validating preprocessing approaches, particularly in the context of batch effect correction and missing value imputation, for reliably analyzing data in biomarker discovery and disease research.}, } @article {pmid38902525, year = {2024}, author = {Kitamura, A and Fujimoto, A and Kawashima, R and Lyu, Y and Sasaki, K and Hamada, Y and Moriya, K and Kurata, A and Takahashi, K and Brielmann, R and Bott, LC and Morimoto, RI and Kinjo, M}, title = {Hetero-oligomerization of TDP-43 carboxy-terminal fragments with cellular proteins contributes to proteotoxicity.}, journal = {Communications biology}, volume = {7}, number = {1}, pages = {743}, pmid = {38902525}, issn = {2399-3642}, support = {JP22gm6410028//Japan Agency for Medical Research and Development (AMED)/ ; JP22ym0126814//Japan Agency for Medical Research and Development (AMED)/ ; 24H02286//MEXT | Japan Society for the Promotion of Science (JSPS)/ ; 22H04826//MEXT | Japan Society for the Promotion of Science (JSPS)/ ; 16KK0156//MEXT | Japan Society for the Promotion of Science (JSPS)/ ; 18K06201//MEXT | Japan Society for the Promotion of Science (JSPS)/ ; 22H02578//MEXT | Japan Society for the Promotion of Science (JSPS)/ ; 22K19886//MEXT | Japan Society for the Promotion of Science (JSPS)/ ; JPMJSP2119//MEXT | Japan Science and Technology Agency (JST)/ ; JPMJFS2101//MEXT | Japan Science and Technology Agency (JST)/ ; }, mesh = {*DNA-Binding Proteins/metabolism/chemistry/genetics ; Humans ; Animals ; Protein Multimerization ; Caenorhabditis elegans/metabolism/genetics ; Intrinsically Disordered Proteins/chemistry/metabolism/genetics ; }, abstract = {Carboxy terminal fragments (CTFs) of TDP-43 contain an intrinsically disordered region (IDR) and form cytoplasmic condensates containing amyloid fibrils. Such condensates are toxic and associated with pathogenicity in amyotrophic lateral sclerosis. However, the molecular details of how the domain of TDP-43 CTFs leads to condensation and cytotoxicity remain elusive. Here, we show that truncated RNA/DNA-recognition motif (RRM) at the N-terminus of TDP-43 CTFs leads to the structural transition of the IDR, whereas the IDR itself of TDP-43 CTFs is difficult to assemble even if they are proximate intermolecularly. Hetero-oligomers of TDP-43 CTFs that have recruited other proteins are more toxic than homo-oligomers, implicating loss-of-function of the endogenous proteins by such oligomers is associated with cytotoxicity. Furthermore, such toxicity of TDP-43 CTFs was cell-nonautonomously affected in the nematodes. Therefore, misfolding and oligomeric characteristics of the truncated RRM at the N-terminus of TDP-43 CTFs define their condensation properties and toxicity.}, } @article {pmid38901111, year = {2024}, author = {Pavey, NA and Menon, P and Peterchev, AV and Kiernan, MC and Vucic, S}, title = {Abnormalities of cortical stimulation strength-duration time constant in amyotrophic lateral sclerosis.}, journal = {Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology}, volume = {164}, number = {}, pages = {161-167}, pmid = {38901111}, issn = {1872-8952}, support = {R01 MH128422/MH/NIMH NIH HHS/United States ; R01 NS117405/NS/NINDS NIH HHS/United States ; RF1 MH124943/MH/NIMH NIH HHS/United States ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology/diagnosis ; Male ; Female ; *Transcranial Magnetic Stimulation/methods ; Middle Aged ; *Motor Cortex/physiopathology ; Aged ; *Evoked Potentials, Motor/physiology ; Adult ; Motor Neurons/physiology ; }, abstract = {OBJECTIVES: Strength-duration time constant (SDTC) may now be determined for cortical motor neurones, with activity mediated by transient Na[+] conductances. The present study determined whether cortical SDTC is abnormal and linked to the pathogenesis of amyotrophic lateral sclerosis.

METHODS: Cortical SDTC and rheobase were estimated from 17 ALS patients using a controllable pulse parameter transcranial magnetic stimulation (cTMS) device. Resting motor thresholds (RMTs) were determined at pulse widths (PW) of 30, 45, 60, 90 and 120 µs and M-ratio of 0.1, using a figure-of-eight coil applied to the primary motor cortex.

RESULTS: SDTC was significantly reduced in ALS patients (150.58 ± 9.98 µs; controls 205.94 ± 13.7 µs, P < 0.01). The reduced SDTC correlated with a rate of disease progression (Rho = -0.440, P < 0.05), ALS functional rating score (ALSFRS-R) score (Rho = 0.446, P < 0.05), and disease duration (R = 0.428, P < 0.05). The degree of change in SDTC was greater in patients with cognitive abnormalities as manifested by an abnormal total Edinburgh Cognitive ALS Screen score (140.5 ± 28.7 µs, P < 0.001) and ALS-specific subscore (141.7 ± 33.2 µs, P = 0.003).

CONCLUSIONS: Cortical SDTC reduction was associated with a more aggressive ALS phenotype, or with more prominent cognitive impairment.

SIGNIFICANCE: An increase in transient Na[+] conductances may account for the reduction in SDTC, linked to the pathogenesis of ALS.}, } @article {pmid38900989, year = {2024}, author = {Tahedl, M and Tan, EL and Kleinerova, J and Delaney, S and Hengeveld, JC and Doherty, MA and Mclaughlin, RL and Pradat, PF and Raoul, C and Ango, F and Hardiman, O and Chang, KM and Lope, J and Bede, P}, title = {Progressive Cerebrocerebellar Uncoupling in Sporadic and Genetic Forms of Amyotrophic Lateral Sclerosis.}, journal = {Neurology}, volume = {103}, number = {2}, pages = {e209623}, doi = {10.1212/WNL.0000000000209623}, pmid = {38900989}, issn = {1526-632X}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/diagnostic imaging/pathology/physiopathology ; Male ; Female ; Middle Aged ; *Cerebellum/diagnostic imaging/pathology ; Aged ; *C9orf72 Protein/genetics ; Prospective Studies ; Ataxin-2/genetics ; Magnetic Resonance Imaging ; Disease Progression ; Cerebral Cortex/diagnostic imaging/pathology/physiopathology ; Adult ; Longitudinal Studies ; }, abstract = {BACKGROUND AND OBJECTIVES: Amyotrophic lateral sclerosis (ALS) is predominantly associated with motor cortex, corticospinal tract (CST), brainstem, and spinal cord degeneration, and cerebellar involvement is much less well characterized. However, some of the cardinal clinical features of ALS, such as dysarthria, dysphagia, gait impairment, falls, and impaired dexterity, are believed to be exacerbated by coexisting cerebellar pathology. Cerebellar pathology may also contribute to cognitive, behavioral, and pseudobulbar manifestations. Our objective was to systematically assess both intracerebellar pathology and cerebrocerebellar connectivity alterations in a genetically stratified cohort of ALS.

METHODS: A prospective, multimodal neuroimaging study was conducted to evaluate the longitudinal evolution of intracerebellar pathology and cerebrocerebellar connectivity, using structural and functional measures.

RESULTS: A total of 113 healthy controls and 212 genetically stratified individuals with ALS were included: (1) C9orf72 hexanucleotide carriers ("C9POS"), (2) sporadic patients who tested negative for ALS-associated genetic variants, and (3) intermediate-length CAG trinucleotide carriers in ATXN2 ("ATXN2"). Flocculonodular lobule (padj = 0.014, 95% CI -5.06e-5 to -3.98e-6) and crura (padj = 0.031, 95% CI -1.63e-3 to -5.55e-5) volume reductions were detected at baseline in sporadic patients. Cerebellofrontal and cerebelloparietal structural connectivity impairment was observed in both C9POS and sporadic patients at baseline, and both projections deteriorated further over time in sporadic patients (padj = 0.003, t(249) = 3.04 and padj = 0.05, t(249) = 1.93). Functional cerebelloparietal uncoupling was evident in sporadic patients at baseline (padj = 0.004, 95% CI -0.19 to -0.03). ATXN2 patients exhibited decreased cerebello-occipital functional connectivity at baseline (padj = 0.004, 95% CI -0.63 to -0.06), progressive cerebellotemporal functional disconnection (padj = 0.025, t(199) = -2.26), and progressive flocculonodular lobule degeneration (padj = 0.017, t(249) = -2.24). C9POS patients showed progressive ventral dentate atrophy (padj = 0.007, t(249) = -2.75). The CSTs (padj < 0.001, 95% CI 4.89e-5 to 1.14e-4) and transcallosal interhemispheric fibers (padj < 0.001, 95% CI 5.21e-5 to 1.31e-4) were affected at baseline in C9POS and exhibited rapid degeneration over the 4 time points. The rate of decline in CST and corpus callosum integrity was faster than the rate of cerebrocerebellar disconnection (padj = 0.001, t(190) = 6.93).

DISCUSSION: ALS is associated with accruing intracerebellar disease burden as well as progressive corticocerebellar uncoupling. Contrary to previous suggestions, we have not detected evidence of compensatory structural or functional changes in response to supratentorial degeneration. The contribution of cerebellar disease burden to dysarthria, dysphagia, gait impairment, pseudobulbar affect, and cognitive deficits should be carefully considered in clinical assessments, monitoring, and multidisciplinary interventions.}, } @article {pmid38900757, year = {2024}, author = {Serian, A and Finsel, J and Ludolph, AC and Uttner, I and Lulé, D}, title = {Screening instruments of cognition: The relation of the mini-mental state examination to the Edinburgh cognitive and behavioural ALS screen in amyotrophic lateral sclerosis.}, journal = {PloS one}, volume = {19}, number = {6}, pages = {e0304593}, pmid = {38900757}, issn = {1932-6203}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/psychology/complications/epidemiology ; Male ; Female ; Middle Aged ; Aged ; *Mental Status and Dementia Tests ; Cognition/physiology ; Cognitive Dysfunction/diagnosis/epidemiology ; Neuropsychological Tests ; Cognition Disorders/diagnosis ; }, abstract = {OBJECTIVE: The Edinburgh Cognitive and Behavioural ALS Screen (ECAS) is an established cognitive screening instrument for patients with amyotrophic lateral sclerosis (ALS). Different from tools like the Mini-Mental State Examination (MMSE), it is adjusted for motor impairment, yet, the latter remains one of the most widely used screening instruments, also in ALS studies. Thus, it is of utmost importance to relate outcome scores of both instruments to allow for comparison in ALS patients. This study reports on the performance of ALS patients in both tests with regard to incidence and degree of cognitive impairment, and the correspondence of both, ECAS and MMSE scores.

METHODS: We examined N = 84 ALS patients with the German versions of the ECAS and the MMSE. Performance in both tests regarding incidence and degree of cognitive impairment, and correspondence of frequency of cognitive impairment according to both tests was examined. The relationship between ECAS and MMSE scores was modelled with a non-linear regression model.

RESULTS: All ALS patients were able to complete the ECAS, 89.3% (N = 75) were capable to complete the MMSE. Prevalence of cognitive impairment was in both tests 22.7%, however agreement was only 52.9%. Despite, regression analyses yielded a strong positive relationship (adjusted R2 = .68) between the ECAS total score and the MMSE total score. Both tests were able to identify all patients with dementia.

CONCLUSION: These results suggest that the MMSE is not ideal for cognitive screening in early-stage ALS patients. However, a rough translation of MMSE scores in ECAS scores is possible to estimate the cognitive performance level of patients, with the ECAS being more discriminative in the lower range of cognitive dysfunction (ECAS score: 80-136), for which the MMSE does not define cognitive impairment (corresponding MMSE score: 27-30).}, } @article {pmid38900570, year = {2024}, author = {Privado, J and Sanchis Sanchis, E and Sancho-Cantus, D and Cubero-Plazas, L and Navarro-Illana, E and de la Rubia Ortí, JE}, title = {Prediction of caregiver psychological distress in amyotrophic lateral sclerosis: A cross-sectional study.}, journal = {Rehabilitation psychology}, volume = {69}, number = {4}, pages = {364-374}, doi = {10.1037/rep0000554}, pmid = {38900570}, issn = {1939-1544}, support = {//Catholic University of Valencia San Vicente Mártir/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/psychology/complications ; Male ; *Caregivers/psychology ; Female ; Cross-Sectional Studies ; Middle Aged ; *Psychological Distress ; Aged ; Adult ; Stress, Psychological/psychology/complications ; }, abstract = {PURPOSE/OBJECTIVE: To propose a predictive model for caregivers' psychological distress (including anxiety, depression, and cognitive overload) based on different data gathered from amyotrophic lateral sclerosis (ALS) patients (cognitive level, psychological distress, type of ALS, and sex).

RESEARCH METHOD/DESIGN: A cross-sectional study with a sample of 51 ALS patients and their respective main carers. Various instruments were used such as the Beck Anxiety Inventory, ALS Depression Inventory-12, and the Edinburgh Cognitive and Behavioral ALS Screen, Zarit Burden Interview, Self-Rating Depression Scale, and Self-Rating Anxiety Scale for caregivers.

RESULTS: ALS type, sex, and cognition were predictive variables for caregiver distress, with the main explanatory variable being the distress of the patients themselves. Spinal ALS led to higher psychological distress in caregivers (β = .38), as did male patients with ALS and preserved cognition.

CONCLUSIONS/IMPLICATIONS: The proposed confirmatory model demonstrates that patients' psychological distress is the best predictor of psychological distress in their caregivers. (PsycInfo Database Record (c) 2024 APA, all rights reserved).}, } @article {pmid38898687, year = {2024}, author = {Lee, B and Lee, SM and Song, JW and Choi, JW}, title = {Gut Microbiota Metabolite Messengers in Brain Function and Pathology at a View of Cell Type-Based Receptor and Enzyme Reaction.}, journal = {Biomolecules & therapeutics}, volume = {32}, number = {4}, pages = {403-423}, pmid = {38898687}, issn = {1976-9148}, abstract = {The human gastrointestinal (GI) tract houses a diverse microbial community, known as the gut microbiome comprising bacteria, viruses, fungi, and protozoa. The gut microbiome plays a crucial role in maintaining the body's equilibrium and has recently been discovered to influence the functioning of the central nervous system (CNS). The communication between the nervous system and the GI tract occurs through a two-way network called the gut-brain axis. The nervous system and the GI tract can modulate each other through activated neuronal cells, the immune system, and metabolites produced by the gut microbiome. Extensive research both in preclinical and clinical realms, has highlighted the complex relationship between the gut and diseases associated with the CNS, such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. This review aims to delineate receptor and target enzymes linked with gut microbiota metabolites and explore their specific roles within the brain, particularly their impact on CNS-related diseases.}, } @article {pmid38898538, year = {2024}, author = {Bravo-Miana, RDC and Arizaga-Echebarria, JK and Otaegui, D}, title = {Central nervous system-derived extracellular vesicles: the next generation of neural circulating biomarkers?.}, journal = {Translational neurodegeneration}, volume = {13}, number = {1}, pages = {32}, pmid = {38898538}, issn = {2047-9158}, support = {PI20/1253//Instituto de Salud Carlos III/ ; KK-2021/00009//Departamento de Desarrollo Económico, Sostenibilidad y Medio Ambiente/ ; ECTRIMS Postdoctoral Research Fellowship 2023//European Committee for Treatment and Research in Multiple Sclerosis/ ; Predoctoral fellowship//Basque Government/ ; }, mesh = {Humans ; *Extracellular Vesicles/metabolism ; *Biomarkers/blood ; *Central Nervous System/metabolism ; *Neurodegenerative Diseases/blood/diagnosis/metabolism ; Animals ; }, abstract = {The central nervous system (CNS) is integrated by glial and neuronal cells, and both release extracellular vesicles (EVs) that participate in CNS homeostasis. EVs could be one of the best candidates to operate as nanosized biological platforms for analysing multidimensional bioactive cargos, which are protected during systemic circulation of EVs. Having a window into the molecular level processes that are happening in the CNS could open a new avenue in CNS research. This raises a particular point of interest: can CNS-derived EVs in blood serve as circulating biomarkers that reflect the pathological status of neurological diseases? L1 cell adhesion molecule (L1CAM) is a widely reported biomarker to identify CNS-derived EVs in peripheral blood. However, it has been demonstrated that L1CAM is also expressed outside the CNS. Given that principal data related to neurodegenerative diseases, such as multiple sclerosis, amyotrophic lateral sclerosis, Parkinson's disease and Alzheimer's disease were obtained using L1CAM-positive EVs, efforts to overcome present challenges related to its specificity are required. In this sense, other surface biomarkers for CNS-derived EVs, such as glutamate aspartate transporter (GLAST) and myelin oligodendrocyte glycoprotein (MOG), among others, have started to be used. Establishing a panel of EV biomarkers to analyse CNS-derived EVs in blood could increase the specificity and sensitivity necessary for these types of studies. This review covers the main evidence related to CNS-derived EVs in cerebrospinal fluid and blood samples of patients with neurological diseases, focusing on the reported biomarkers and the technical possibilities for their isolation. EVs are emerging as a mirror of brain physiopathology, reflecting both localized and systemic changes. Therefore, when the technical hindrances for EV research and clinical applications are overcome, novel disease-specific panels of EV biomarkers would be discovered to facilitate transformation from traditional medicine to personalized medicine.}, } @article {pmid38898231, year = {2024}, author = {Gao, J and Gunasekar, S and Xia, ZJ and Shalin, K and Jiang, C and Chen, H and Lee, D and Lee, S and Pisal, ND and Luo, JN and Griciuc, A and Karp, JM and Tanzi, R and Joshi, N}, title = {Gene therapy for CNS disorders: modalities, delivery and translational challenges.}, journal = {Nature reviews. Neuroscience}, volume = {25}, number = {8}, pages = {553-572}, pmid = {38898231}, issn = {1471-0048}, mesh = {Humans ; *Genetic Therapy/methods/trends ; *Central Nervous System Diseases/therapy/genetics ; Animals ; Translational Research, Biomedical/methods ; Gene Transfer Techniques/trends ; }, abstract = {Gene therapy is emerging as a powerful tool to modulate abnormal gene expression, a hallmark of most CNS disorders. The transformative potentials of recently approved gene therapies for the treatment of spinal muscular atrophy (SMA), amyotrophic lateral sclerosis (ALS) and active cerebral adrenoleukodystrophy are encouraging further development of this approach. However, most attempts to translate gene therapy to the clinic have failed to make it to market. There is an urgent need not only to tailor the genes that are targeted to the pathology of interest but to also address delivery challenges and thereby maximize the utility of genetic tools. In this Review, we provide an overview of gene therapy modalities for CNS diseases, emphasizing the interconnectedness of different delivery strategies and routes of administration. Important gaps in understanding that could accelerate the clinical translatability of CNS genetic interventions are addressed, and we present lessons learned from failed clinical trials that may guide the future development of gene therapies for the treatment and management of CNS disorders.}, } @article {pmid38898006, year = {2024}, author = {Nógrádi, B and Nógrádi-Halmi, D and Erdélyi-Furka, B and Kádár, Z and Csont, T and Gáspár, R}, title = {Mechanism of motoneuronal and pyramidal cell death in amyotrophic lateral sclerosis and its potential therapeutic modulation.}, journal = {Cell death discovery}, volume = {10}, number = {1}, pages = {291}, pmid = {38898006}, issn = {2058-7716}, support = {BO/00574/22//Magyar Tudományos Akadémia (Hungarian Academy of Sciences)/ ; ÚNKP-23-5 -SZTE-711//Emberi Eroforrások Minisztériuma (Ministry of Human Capacities)/ ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder clinically characterized by muscle atrophy and progressive paralysis. Loss of motoneurons and pyramidal cells is thought to be the center piece of the complex and multifaceted ALS pathology, however, the exact mechanisms laying behind motoneuronal cell death in the spinal cord and motor cortex are still unknown. It was originally proposed that apoptosis plays a fundamental role in motoneuronal demise, nonetheless, later it became clear that other forms of regulated cell death, including necroptosis, pyroptosis, ferroptosis, and autophagy-dependent cell death, may also contribute to motoneuron loss. Over the past years, multiple studies aimed to improve our understanding of the contributory role of these mechanisms as well as to offer novel targets for potential therapeutic interventions. The pharmacological inhibition of the ferroptotic pathway and the modulation of the autophagic machinery seem to have particularly promising effects, reducing motoneuron loss and slowing disease progression in transgenic models of ALS. Nevertheless, the potential beneficial effects of necroptosis-targeting interventions were mostly disproven in the latest studies. In this review we aim to summarize the current view on regulated cell death mechanisms that lead to motoneuronal and pyramidal cell degeneration in ALS and showcase their applicability as future drug targets.}, } @article {pmid38897956, year = {2025}, author = {Takahashi, R and Furuta, M and Nagashima, K and Ikeda, Y}, title = {Concurrent Amyotrophic Lateral Sclerosis and Huntington's Disease.}, journal = {Internal medicine (Tokyo, Japan)}, volume = {64}, number = {2}, pages = {297-300}, pmid = {38897956}, issn = {1349-7235}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/complications/genetics/diagnosis ; Huntingtin Protein ; *Huntington Disease/complications/genetics/diagnosis ; Trinucleotide Repeat Expansion ; }, abstract = {Huntington's disease (HD) is a dominantly inherited neurological disorder characterized by chorea, psychiatric symptoms, and cognitive decline but typically lacks muscular atrophy and weakness. We herein report a case of genetically confirmed HD showing progressive systemic weakness with findings of upper and lower motor neuron involvement due to amyotrophic lateral sclerosis (ALS). The current patient and the previously reported cases with complications of HD and ALS indicate that cytosine-adenine-guanine (CAG) repeat expansion in the huntingtin gene might have a pathogenic role in causing the two neurological disorders.}, } @article {pmid38896345, year = {2024}, author = {Robinson, JL and Suh, E and Xu, Y and Hurtig, HI and Elman, L and McMillan, CT and Irwin, DJ and Porta, S and Van Deerlin, VM and Lee, EB}, title = {Annexin A11 aggregation in FTLD-TDP type C and related neurodegenerative disease proteinopathies.}, journal = {Acta neuropathologica}, volume = {147}, number = {1}, pages = {104}, pmid = {38896345}, issn = {1432-0533}, support = {RF1 AG065341/AG/NIA NIH HHS/United States ; U19 AG062418/AG/NIA NIH HHS/United States ; P30 AG072979/AG/NIA NIH HHS/United States ; P01AG066597/AG/NIA NIH HHS/United States ; U19AG062418/AG/NIA NIH HHS/United States ; R01 AG075276/AG/NIA NIH HHS/United States ; P01 AG066597/AG/NIA NIH HHS/United States ; P30AG072979/AG/NIA NIH HHS/United States ; RF1AG065341/AG/NIA NIH HHS/United States ; }, mesh = {Humans ; Aged ; *Annexins/genetics/metabolism ; Female ; Male ; *DNA-Binding Proteins/genetics/metabolism ; *Frontotemporal Lobar Degeneration/genetics/pathology/metabolism ; Middle Aged ; Aged, 80 and over ; TDP-43 Proteinopathies/pathology/genetics ; Neurodegenerative Diseases/pathology/genetics/metabolism ; Amyotrophic Lateral Sclerosis/genetics/pathology/metabolism ; Inclusion Bodies/pathology/metabolism ; Brain/pathology/metabolism ; Protein Aggregation, Pathological/pathology/genetics/metabolism ; }, abstract = {TAR DNA-binding protein 43 (TDP-43) is an RNA binding protein found within ribonucleoprotein granules tethered to lysosomes via annexin A11. TDP-43 protein forms inclusions in many neurodegenerative diseases including amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-TDP) and limbic predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC). Annexin A11 is also known to form aggregates in ALS cases with pathogenic variants in ANXA11. Annexin A11 aggregation has not been described in sporadic ALS, FTLD-TDP or LATE-NC cases. To explore the relationship between TDP-43 and annexin A11, genetic analysis of 822 autopsy cases was performed to identify rare ANXA11 variants. In addition, an immunohistochemical study of 368 autopsy cases was performed to identify annexin A11 aggregates. Insoluble annexin A11 aggregates which colocalize with TDP-43 inclusions were present in all FTLD-TDP Type C cases. Annexin A11 inclusions were also seen in a small proportion (3-6%) of sporadic and genetic forms of FTLD-TDP types A and B, ALS, and LATE-NC. In addition, we confirm the comingling of annexin A11 and TDP-43 aggregates in an ALS case with the pathogenic ANXA11 p.G38R variant. Finally, we found abundant annexin A11 inclusions as the primary pathologic finding in a case of progressive supranuclear palsy-like frontotemporal dementia with prominent striatal vacuolization due to a novel variant, ANXA11 p.P75S. By immunoblot, FTLD-TDP with annexinopathy and ANXA11 variant cases show accumulation of insoluble ANXA11 including a truncated fragment. These results indicate that annexin A11 forms a diverse and heterogeneous range of aggregates in both sporadic and genetic forms of TDP-43 proteinopathies. In addition, the finding of a primary vacuolar annexinopathy due to ANXA11 p.P75S suggests that annexin A11 aggregation is sufficient to cause neurodegeneration.}, } @article {pmid38896262, year = {2024}, author = {Shen, D and Yang, X and He, D and Zhang, K and Liu, S and Sun, X and Li, J and Cai, Z and Liu, M and Zhang, X and Liu, Q and Cui, L}, title = {Clinical and genetic characteristics of 1672 cases of amyotrophic lateral sclerosis in China: a single-center retrospective study.}, journal = {Journal of neurology}, volume = {271}, number = {8}, pages = {5541-5548}, pmid = {38896262}, issn = {1432-1459}, support = {XDB39040100//Strategic Priority Research Program (Pilot study) "Biological basis of aging and therapeutic strategies" of the Chinese Academy of Sciences/ ; 2022-PUMCH-B-017//High-level Hospital Construction Project of Guangdong Provincial People's Hospital/ ; 2022YFC2703904//Key Technologies Research and Development Program/ ; 2021-I2M-1-034//Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences/ ; 81971293//National Natural Science Foundation of China/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/epidemiology ; Male ; Middle Aged ; Female ; Adult ; Aged ; Young Adult ; Adolescent ; Aged, 80 and over ; China/epidemiology ; Retrospective Studies ; *C9orf72 Protein/genetics ; Age of Onset ; Mutation ; Phenotype ; Exome Sequencing ; Genotype ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease. In recent years, continuous discoveries of new ALS-causing genes have enhanced the understanding of the genotype-phenotype relationship in ALS, aiding in disease progression prediction and providing a more comprehensive basis for genetic diagnosis.

METHODS: A total of 1672 ALS patients who visited the Neurology Department of Peking Union Medical College Hospital between January 2014 and December 2022 and met the revised El Escorial diagnostic criteria were included. Clinical data were collected, whole exome sequencing and dynamic mutation screening of the C9ORF72 gene were performed, and the clinical phenotypes and genotypes of the patients were analyzed.

RESULTS: The average age of onset for the 1672 ALS patients was 52.6 ± 11.2 years (range 17-85 years), with a median disease duration of 14 months at the time of visit (interquartile range 9-24 months, range 2-204 months). The male to female ratio was 833:839. The patients included 297 (17.8%) with bulbar onset, 198 (11.8%) with flail arm/leg syndrome, 89 (5.3%) with familial ALS, and 52 (3.1%) with concomitant frontotemporal dementia (FTD). Pathogenic variants associated with ALS were detected in 175 patients (10.5% of the cohort), with the most common mutations being SOD1, FUS, and ANXA11. Among patients with familial ALS, 56.2% (50/89) had genetic mutations, compared to 7.9% (125/1583) in sporadic ALS cases. From the perspective of phenotype-genotype correlation, (1) In ALS-FTD patients, the most common genetic mutations were ANXA11 and C9ORF72 repeat expansions. Patients with flail arm/leg syndrome more frequently carried mutations in SOD1, ANXA11, and hnRNPA1; (2) Despite genetic heterogeneity, it was observed that mutations in FUS and NEK1 were more common in males, and patients with FUS mutations had a younger age of onset; mutations in SOD1 and SQSTM1 were more likely to present with lower limb onset.

CONCLUSION: This study provides comprehensive data on the genetic characteristics of ALS patients in China through large-scale clinical data and genetic analysis of 1672 cases. Differences in age of onset, onset site, and clinical phenotype among ALS patients with different genotypes can help clinicians better predict disease progression and provide a basis for precise diagnosis and individualized treatment.}, } @article {pmid38896163, year = {2024}, author = {Woodworth, DC and Nguyen, KM and Sordo, L and Scambray, KA and Head, E and Kawas, CH and Corrada, MM and Nelson, PT and Sajjadi, SA}, title = {Comprehensive assessment of TDP-43 neuropathology data in the National Alzheimer's Coordinating Center database.}, journal = {Acta neuropathologica}, volume = {147}, number = {1}, pages = {103}, pmid = {38896163}, issn = {1432-0533}, support = {P20 AG068053/AG/NIA NIH HHS/United States ; P30 AG066515/AG/NIA NIH HHS/United States ; P30 AG062421/AG/NIA NIH HHS/United States ; P30 AG066508/AG/NIA NIH HHS/United States ; P30 AG066519/AG/NIA NIH HHS/United States ; P30 AG066462/AG/NIA NIH HHS/United States ; P30 AG066509/AG/NIA NIH HHS/United States ; P20 AG068077/AG/NIA NIH HHS/United States ; P30 AG066546/AG/NIA NIH HHS/United States ; P30 AG072972/AG/NIA NIH HHS/United States ; P20 AG068082/AG/NIA NIH HHS/United States ; P30 AG072975/AG/NIA NIH HHS/United States ; P30 AG066444/AG/NIA NIH HHS/United States ; P30 AG066507/AG/NIA NIH HHS/United States ; P30 AG072946/AG/NIA NIH HHS/United States ; P30 AG066518/AG/NIA NIH HHS/United States ; T32AG073088/AG/NIA NIH HHS/United States ; P30 AG066511/AG/NIA NIH HHS/United States ; U24 AG072122/AG/NIA NIH HHS/United States ; P30 AG066512/AG/NIA NIH HHS/United States ; P30 AG072978/AG/NIA NIH HHS/United States ; P30 AG062429/AG/NIA NIH HHS/United States ; T32 AG073088/AG/NIA NIH HHS/United States ; P30 AG072973/AG/NIA NIH HHS/United States ; P30 AG062422/AG/NIA NIH HHS/United States ; R01 AG079280/AG/NIA NIH HHS/United States ; R01 AG062706/AG/NIA NIH HHS/United States ; P30 AG066530/AG/NIA NIH HHS/United States ; P30 AG072977/AG/NIA NIH HHS/United States ; P30 AG062677/AG/NIA NIH HHS/United States ; P20 AG068024/AG/NIA NIH HHS/United States ; P30 AG072958/AG/NIA NIH HHS/United States ; P30 AG062715/AG/NIA NIH HHS/United States ; P30 AG066506/AG/NIA NIH HHS/United States ; P30 AG066468/AG/NIA NIH HHS/United States ; P30 AG072976/AG/NIA NIH HHS/United States ; RF1 AG082339/AG/NIA NIH HHS/United States ; P30 AG072947/AG/NIA NIH HHS/United States ; P30 AG072931/AG/NIA NIH HHS/United States ; P30 AG066514/AG/NIA NIH HHS/United States ; P30 AG072959/AG/NIA NIH HHS/United States ; R01AG062706/AG/NIA NIH HHS/United States ; P30 AG072979/AG/NIA NIH HHS/United States ; }, mesh = {Humans ; Female ; Aged ; Male ; *Alzheimer Disease/pathology/metabolism ; *DNA-Binding Proteins/metabolism ; *TDP-43 Proteinopathies/pathology ; Aged, 80 and over ; Databases, Factual ; Frontotemporal Lobar Degeneration/pathology/metabolism ; Brain/pathology/metabolism ; Amyotrophic Lateral Sclerosis/pathology/metabolism ; Hippocampus/pathology/metabolism ; Middle Aged ; }, abstract = {TDP-43 proteinopathy is a salient neuropathologic feature in a subset of frontotemporal lobar degeneration (FTLD-TDP), in amyotrophic lateral sclerosis (ALS-TDP), and in limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC), and is associated with hippocampal sclerosis of aging (HS-A). We examined TDP-43-related pathology data in the National Alzheimer's Coordinating Center (NACC) in two parts: (I) availability of assessments, and (II) associations with clinical diagnoses and other neuropathologies in those with all TDP-43 measures available. Part I: Of 4326 participants with neuropathology data collected using forms that included TDP-43 assessments, data availability was highest for HS-A (97%) and ALS (94%), followed by FTLD-TDP (83%). Regional TDP-43 pathologic assessment was available for 77% of participants, with hippocampus the most common region. Availability for the TDP-43-related measures increased over time, and was higher in centers with high proportions of participants with clinical FTLD. Part II: In 2142 participants with all TDP-43-related assessments available, 27% of participants had LATE-NC, whereas ALS-TDP or FTLD-TDP (ALS/FTLD-TDP) was present in 9% of participants, and 2% of participants had TDP-43 related to other pathologies ("Other TDP-43"). HS-A was present in 14% of participants, of whom 55% had LATE-NC, 20% ASL/FTLD-TDP, 3% Other TDP-43, and 23% no TDP-43. LATE-NC, ALS/FTLD-TDP, and Other TDP-43, were each associated with higher odds of dementia, HS-A, and hippocampal atrophy, compared to those without TDP-43 pathology. LATE-NC was associated with higher odds for Alzheimer's disease (AD) clinical diagnosis, AD neuropathologic change (ADNC), Lewy bodies, arteriolosclerosis, and cortical atrophy. ALS/FTLD-TDP was associated with higher odds of clinical diagnoses of primary progressive aphasia and behavioral-variant frontotemporal dementia, and cortical/frontotemporal lobar atrophy. When using NACC data for TDP-43-related analyses, researchers should carefully consider the incomplete availability of the different regional TDP-43 assessments, the high frequency of participants with ALS/FTLD-TDP, and the presence of other forms of TDP-43 pathology.}, } @article {pmid38895672, year = {2024}, author = {Deng, J and Sun, WT and Gong, K and Wang, LP and Li, FZ}, title = {Internal limiting membrane peeling combined with silicone oil or air tamponade for highly myopic foveoschisis.}, journal = {International journal of ophthalmology}, volume = {17}, number = {6}, pages = {1079-1085}, pmid = {38895672}, issn = {2222-3959}, abstract = {AIM: To compare the efficacy of pars plana vitrectomy (PPV) combined with internal limiting membrane (ILM) and silicone oil or sterile air tamponade for the treatment of myopic foveoschisis (MF) in highly myopic eyes.

METHODS: This retrospective study included 48 myopic eyes of 40 patients with MF and axial lengths (ALs) ranging from 26-32 mm treated between January 2020 and January 2022. All patients were underwent PPV combined with ILM peeling followed by sterile air or silicone oil tamponade and followed up at least 12mo. Based on the features on spectral-domain optical coherence tomography (SD-OCT), the eyes were divided into the MF-only group (Group A, n=15 eyes), MF with central foveal detachment group (Group B, n=20 eyes), and MF with lamellar macular hole group (Group C, n=13 eyes). According to AL, eyes were further divided into three groups: Group D (26.01-28.00 mm, n=12 eyes), Group E (28.01-30.00 mm, n=26 eyes), and Group F (30.01-32.00 mm, n=10 eyes). The best-corrected visual acuity (BCVA), central foveal thickness (CFT), and complications were recorded.

RESULTS: The patients included 16 males and 24 females with the mean age of 56±9.82y. The BCVA and CFT improved in all groups after surgery (P<0.01), while there was no significant difference of the CFT in Group A, B, and C postoperatively (P>0.05). The intergroup differences of BCVA and CFT postoperatively were statistically significant in Group D, E, and F. Twenty eyes were injected with sterile air, and 28 eyes were injected with silicone oil for tamponade based on the AL. However, there was no statistically significant difference among Groups D, E, and F in terms of the results of sterile air or silicone oil tamponade. The mean recovery time was 5.9mo for MF patients subjected to silicone oil tamponade and 7.7mo for patients subjected to sterile air tamponade, and the difference was not statistically significant.

CONCLUSION: PPV and ILM peeling combined with silicone oil or sterile air tamponade can achieve good results for MF in highly myopic eyes with ALs≤32 mm.}, } @article {pmid38895610, year = {2024}, author = {Kaundun, SS and Martin-Sanz, A and Rodríguez, M and Serbanoiu, T and Moreno, J and Mcindoe, E and le Goupil, G}, title = {First case of evolved herbicide resistance in the holoparasite sunflower broomrape, Orobanche cumana Wallr.}, journal = {Frontiers in plant science}, volume = {15}, number = {}, pages = {1420009}, pmid = {38895610}, issn = {1664-462X}, abstract = {The development and commercialisation of sunflower varieties tolerant to acetolactate synthase (ALS)-inhibiting herbicides some 20 years ago provided farmers with an alternative method for the cost-effective control of Orobanche cumana. In 2020, however, two independent sunflower broomrape populations from Drama (GR-DRA) and Orestiada (GR-ORE), Greece, were reported to be heavily infested with O. cumana after application of the ALS-inhibiting herbicide imazamox. Here we have investigated the race of GR-DRA and GR-ORE and determined the basis of resistance to imazamox in the two Greek O. cumana samples. Using a set of five diagnostic sunflower varieties characterised by different resistant genes with respect to O. cumana infestation, we have clearly established that the GR-ORE and GR-DRA populations belong to the invasive broomrape races G and G+, respectively. Live underground tubercles and emerged shoots were identified at the recommended field rate of imazamox for GR-DRA and GR-ORE but not for two other standard sensitive populations in a whole plant dose response test using two different herbicide-tolerant sunflower hybrids as hosts. Sequencing of the ALS gene identified an alanine 205 to aspartate mutation in all GR-ORE samples. Most GR-DRA tubercles were characterised by a second serine 653 to asparagine ALS mutation whilst a few GR-DRA individuals contained the A205D mutation. Mutations at ALS codons 205 and 653 are known to impact on the binding and efficacy of imazamox and other imidazolinone herbicides. The knowledge generated here will be important for tracking and managing broomrape resistance to ALS-inhibiting herbicides in sunflower growing regions.}, } @article {pmid38895380, year = {2024}, author = {König, LE and Rodriguez, S and Hug, C and Daneshvari, S and Chung, A and Bradshaw, GA and Sahin, A and Zhou, G and Eisert, RJ and Piccioni, F and Das, S and Kalocsay, M and Sokolov, A and Sorger, P and Root, DE and Albers, MW}, title = {TYK2 as a novel therapeutic target in Alzheimer's Disease with TDP-43 inclusions.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {38895380}, issn = {2692-8205}, support = {R01 AG058063/AG/NIA NIH HHS/United States ; U54 CA225088/CA/NCI NIH HHS/United States ; }, abstract = {Neuroinflammation is a pathological feature of many neurodegenerative diseases, including Alzheimer's disease (AD)[1,2] and amyotrophic lateral sclerosis (ALS)[3], raising the possibility of common therapeutic targets. We previously established that cytoplasmic double-stranded RNA (cdsRNA) is spatially coincident with cytoplasmic pTDP-43 inclusions in neurons of patients with C9ORF72-mediated ALS[4]. CdsRNA triggers a type-I interferon (IFN-I)-based innate immune response in human neural cells, resulting in their death[4]. Here, we report that cdsRNA is also spatially coincident with pTDP-43 cytoplasmic inclusions in brain cells of patients with AD pathology and that type-I interferon response genes are significantly upregulated in brain regions affected by AD. We updated our machine-learning pipeline DRIAD-SP (Drug Repurposing In Alzheimer's Disease with Systems Pharmacology) to incorporate cryptic exon (CE) detection as a proxy of pTDP-43 inclusions and demonstrated that the FDA-approved JAK inhibitors baricitinib and ruxolitinib that block interferon signaling show a protective signal only in cortical brain regions expressing multiple CEs. Furthermore, the JAK family member TYK2 was a top hit in a CRISPR screen of cdsRNA-mediated death in differentiated human neural cells. The selective TYK2 inhibitor deucravacitinib, an FDA-approved drug for psoriasis, rescued toxicity elicited by cdsRNA. Finally, we identified CCL2, CXCL10, and IL-6 as candidate predictive biomarkers for cdsRNA-related neurodegenerative diseases. Together, we find parallel neuroinflammatory mechanisms between TDP-43 associated-AD and ALS and nominate TYK2 as a possible disease-modifying target of these incurable neurodegenerative diseases.}, } @article {pmid38895337, year = {2024}, author = {Vazquez-Sanchez, S and Tilkin, B and Gasset-Rosa, F and Zhang, S and Piol, D and McAlonis-Downes, M and Artates, J and Govea-Perez, N and Verresen, Y and Guo, L and Cleveland, DW and Shorter, J and Da Cruz, S}, title = {Frontotemporal dementia-like disease progression elicited by seeded aggregation and spread of FUS.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2024.06.03.593639}, pmid = {38895337}, issn = {2692-8205}, abstract = {RNA binding proteins have emerged as central players in the mechanisms of many neurodegenerative diseases. In particular, a proteinopathy of fu sed in s arcoma (FUS) is present in some instances of familial Amyotrophic lateral sclerosis (ALS) and about 10% of sporadic FTLD. Here we establish that focal injection of sonicated human FUS fibrils into brains of mice in which ALS-linked mutant or wild-type human FUS replaces endogenous mouse FUS is sufficient to induce focal cytoplasmic mislocalization and aggregation of mutant and wild-type FUS which with time spreads to distal regions of the brain. Human FUS fibril-induced FUS aggregation in the mouse brain of humanized FUS mice is accelerated by an ALS-causing FUS mutant relative to wild-type human FUS. Injection of sonicated human FUS fibrils does not induce FUS aggregation and subsequent spreading after injection into naïve mouse brains containing only mouse FUS, indicating a species barrier to human FUS aggregation and its prion-like spread. Fibril-induced human FUS aggregates recapitulate pathological features of FTLD including increased detergent insolubility of FUS and TAF15 and amyloid-like, cytoplasmic deposits of FUS that accumulate ubiquitin and p62, but not TDP-43. Finally, injection of sonicated FUS fibrils is shown to exacerbate age-dependent cognitive and behavioral deficits from mutant human FUS expression. Thus, focal seeded aggregation of FUS and further propagation through prion-like spread elicits FUS-proteinopathy and FTLD-like disease progression.}, } @article {pmid38895204, year = {2024}, author = {Maitra, S and Baek, M and Choe, YJ and Kim, NC}, title = {FDA-approved PDE4 inhibitors reduce the dominant toxicity of ALS-FTD-associated CHCHD10 [S59L].}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2024.06.04.597429}, pmid = {38895204}, issn = {2692-8205}, abstract = {Mutations in coiled-coil-helix-coiled-coil-helix domain containing 10(CHCHD10) have been identified as a genetic cause of amyotrophic lateral sclerosis and/or frontotemporal dementia(ALS-FTD). In our previous studies using in vivo Drosophila model expressing C2C10H [S81L] , and human cell models expressing CHCHD10 [S59L] , we have identified that the PINK1/Parkin pathway is activated and causes cellular toxicity. Furthermore, we demonstrated that pseudo-substrate inhibitors for PINK1 and mitofusin2 agonists mitigated the cellular toxicity of CHCHD10 [S59L] . Evidences using in vitro/ in vivo genetic and chemical tools indicate that inhibiting PINK1 would be the most promising treatment for CHCHD10 [S59L] -induced diseases. Therefore, we have investigated cellular pathways that can modulate the PINK1/Parkin pathway and reduce CHCHD10 [S59L] -induced cytotoxicity. Here, we report that FDA-approved PDE4 inhibitors reduced CHCHD10 [S59L] -induced morphological and functional mitochondrial defects in human cells and an in vivo Drosophila model expressing C2C10H [S81L] . Multiple PDE4 inhibitors decreased PINK1 accumulation and downstream mitophagy induced by CHCHD10 [S59L] . These findings suggest that PDE4 inhibitors currently available in the market may be repositioned to treat CHCHD10 [S59L] -induced ALS-FTD and possibly other related diseases.}, } @article {pmid38894936, year = {2024}, author = {Brown, SP}, title = {Diagnosis of Cervical Spinal Cord Multiple Sclerosis by a Chiropractic Physician: A Case Report.}, journal = {Cureus}, volume = {16}, number = {6}, pages = {e62618}, pmid = {38894936}, issn = {2168-8184}, abstract = {We present a case report of diagnosis of cervical spine multiple sclerosis by a chiropractic physician. This unique case contributes an account of a challenging differential diagnosis to the literature. A 30-year-old male presented with a three-year history of diffuse left upper extremity motor strength deficits and paresthesia (numbness and tingling). The patient had seen multiple physicians for these symptoms with no diagnosis of multiple sclerosis and no advanced imaging. The differential diagnosis included lower cervical spine nerve root compression or neurological disorders such as amyotrophic lateral sclerosis, cerebral lesion, motor neuropathy, multiple sclerosis, or spinal cord lesion. MRI of the cervical spine with and without IV contrast revealed evidence of spinal cord multiple sclerosis. The patient was referred to a neurologist where the diagnosis of multiple sclerosis was confirmed. A 10-year follow-up showed the patient was controlling his condition with medications and had no disability. This case underscores the importance for physicians to consider neurological conditions and advanced imaging in the presence of diffuse motor strength deficits and paresthesia in the absence of injury, pain, or any other symptoms.}, } @article {pmid38894913, year = {2024}, author = {Sabnis, RW and Sabnis, AR}, title = {Novel Compounds as S1P5 Modulators for Treating Neurodegenerative Diseases.}, journal = {ACS medicinal chemistry letters}, volume = {15}, number = {6}, pages = {750-751}, pmid = {38894913}, issn = {1948-5875}, abstract = {Provided herein are novel compounds as S1P5 modulators, pharmaceutical compositions, use of such compounds in treating neurodegenerative diseases, particularly Alzheimer's disease, multiple sclerosis, migraine and amyotrophic lateral sclerosis, and processes for preparing such compounds.}, } @article {pmid38894662, year = {2024}, author = {Jacobsen, AB and Bostock, H and Howells, J and Cengiz, B and Samusyte, G and Koltzenburg, M and Pia, H and Fuglsang-Frederiksen, A and Blicher, J and Obál, I and Andersen, H and Tankisi, H}, title = {Threshold tracking transcranial magnetic stimulation and neurofilament light chain as diagnostic aids in ALS.}, journal = {Annals of clinical and translational neurology}, volume = {11}, number = {7}, pages = {1887-1896}, pmid = {38894662}, issn = {2328-9503}, support = {//Sundhedsvidenskabelige Fakultet, Aarhus Universitet/ ; R290-2018-751//Lundbeck Foundation/ ; R346-2020-1946//Lundbeck Foundation/ ; //William Demant Fonden/ ; //Familien Hede Nielsens Fond/ ; //Aage og Johanne Louis-Hansens Fond/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/physiopathology ; Middle Aged ; Male ; Female ; Aged ; *Neurofilament Proteins ; *Transcranial Magnetic Stimulation/methods ; *Biomarkers ; Electromyography ; Evoked Potentials, Motor/physiology ; }, abstract = {OBJECTIVE: There is a need for sensitive biomarkers in amyotrophic lateral sclerosis (ALS), to enable earlier diagnosis and to help assess potential treatments. The main objective of this study was to compare two potential biomarkers, threshold-tracking short-interval cortical inhibition (T-SICI), which has shown promise as a diagnostic aid, and neurofilament light chains (NfL).

METHODS: Ninety-seven patients with ALS (mean age 67.1 ± 11.5 years) and 53 ALS mimics (aged 62.4 ± 12.9) were included. Mean disease duration was 14 months ±14.1. Patients were evaluated with revised ALS functional rating score (ALSFRS-R), Penn upper motor neuron score (UMNS), muscle strength using the Medical Research Council (MRC) score and examined with T-SICI, quantitative electromyography (EMG), and NfL measured in spinal fluid.

RESULTS: NfL increased with increasing UMNS (rho = 0.45, p = 8.2 × 10[-6]) whereas T-SICI at 2.5 ms paradoxically increased toward normal values (rho = 0.53, p = 1.9 × 10[-7]). However, these two measures were uncorrelated. Discrimination between ALS patients and mimics was best for NfL (area under ROC curve 0.842, sensitivity 84.9%, specificity 83.5%), compared with T-SICI (0.675, 39.6%, 91.8%). For the patients with no UMN signs, NfL also discriminated best (0.884, 89.3%, 82.6%), compared with T-SICI (0.811, 71.4%, 82.6%). However, when combining NfL and T-SICI, higher AUCs of 0.854 and 0.922 and specificities of 93.8 and 100 were found when considering all patients and patients with no UMN signs, respectively.

INTERPRETATION: Both T-SICI and NfL correlated with UMN involvement and combined, they provided a strong discrimination between ALS patients and ALS mimics.}, } @article {pmid38892814, year = {2024}, author = {Barbato, F and Bombaci, A and Colacicco, G and Bruno, G and Ippolito, D and Pota, V and Dongiovanni, S and Sica, G and Bocchini, G and Valente, T and Scaglione, M and Mainenti, PP and Guarino, S}, title = {Chest Dynamic MRI as Early Biomarker of Respiratory Impairment in Amyotrophic Lateral Sclerosis Patients: A Pilot Study.}, journal = {Journal of clinical medicine}, volume = {13}, number = {11}, pages = {}, pmid = {38892814}, issn = {2077-0383}, abstract = {Background: Amyotrophic lateral sclerosis (ALS) is a neuromuscular progressive disorder characterized by limb and bulbar muscle wasting and weakness. A total of 30% of patients present a bulbar onset, while 70% have a spinal outbreak. Respiratory involvement represents one of the worst prognostic factors, and its early identification is fundamental for the early starting of non-invasive ventilation and for the stratification of patients. Due to the lack of biomarkers of early respiratory impairment, we aimed to evaluate the role of chest dynamic MRI in ALS patients. Methods: We enrolled 15 ALS patients and 11 healthy controls. We assessed the revised ALS functional rating scale, spirometry, and chest dynamic MRI. Data were analyzed by using the Mann-Whitney U test and Cox regression analysis. Results: We observed a statistically significant difference in both respiratory parameters and pulmonary measurements at MRI between ALS patients and healthy controls. Moreover, we found a close relationship between pulmonary measurements at MRI and respiratory parameters, which was statistically significant after multivariate analysis. A sub-group analysis including ALS patients without respiratory symptoms and with normal spirometry values revealed the superiority of chest dynamic MRI measurements in detecting signs of early respiratory impairment. Conclusions: Our data suggest the usefulness of chest dynamic MRI, a fast and economically affordable examination, in the evaluation of early respiratory impairment in ALS patients.}, } @article {pmid38892250, year = {2024}, author = {Cerantonio, A and Citrigno, L and Greco, BM and De Benedittis, S and Passarino, G and Maletta, R and Qualtieri, A and Montesanto, A and Spadafora, P and Cavalcanti, F}, title = {The Role of Mitochondrial Copy Number in Neurodegenerative Diseases: Present Insights and Future Directions.}, journal = {International journal of molecular sciences}, volume = {25}, number = {11}, pages = {}, pmid = {38892250}, issn = {1422-0067}, mesh = {Humans ; *Neurodegenerative Diseases/genetics ; *DNA, Mitochondrial/genetics ; *DNA Copy Number Variations ; *Mitochondria/genetics/metabolism ; Huntington Disease/genetics/pathology ; Animals ; }, abstract = {Neurodegenerative diseases are progressive disorders that affect the central nervous system (CNS) and represent the major cause of premature death in the elderly. One of the possible determinants of neurodegeneration is the change in mitochondrial function and content. Altered levels of mitochondrial DNA copy number (mtDNA-CN) in biological fluids have been reported during both the early stages and progression of the diseases. In patients affected by neurodegenerative diseases, changes in mtDNA-CN levels appear to correlate with mitochondrial dysfunction, cognitive decline, disease progression, and ultimately therapeutic interventions. In this review, we report the main results published up to April 2024, regarding the evaluation of mtDNA-CN levels in blood samples from patients affected by Alzheimer's (AD), Parkinson's (PD), and Huntington's diseases (HD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS). The aim is to show a probable link between mtDNA-CN changes and neurodegenerative disorders. Understanding the causes underlying this association could provide useful information on the molecular mechanisms involved in neurodegeneration and offer the development of new diagnostic approaches and therapeutic interventions.}, } @article {pmid38891895, year = {2024}, author = {Dabrowska, S and Turano, E and Scambi, I and Virla, F and Nodari, A and Pezzini, F and Galiè, M and Bonetti, B and Mariotti, R}, title = {A Cellular Model of Amyotrophic Lateral Sclerosis to Study the Therapeutic Effects of Extracellular Vesicles from Adipose Mesenchymal Stem Cells on Microglial Activation.}, journal = {International journal of molecular sciences}, volume = {25}, number = {11}, pages = {}, pmid = {38891895}, issn = {1422-0067}, mesh = {*Amyotrophic Lateral Sclerosis/therapy/metabolism/pathology ; *Extracellular Vesicles/metabolism ; *Microglia/metabolism ; *Mesenchymal Stem Cells/metabolism ; Humans ; *Superoxide Dismutase-1/metabolism/genetics ; Reactive Oxygen Species/metabolism ; Cell Line ; Adipose Tissue/cytology/metabolism ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive degeneration of upper and lower motor neurons (MNs) in the brain and spinal cord, leading to progressive paralysis and death. Increasing evidence indicates that neuroinflammation plays an important role in ALS's pathogenesis and disease progression. Neuroinflammatory responses, primarily driven by activated microglia and astrocytes, and followed by infiltrating peripheral immune cells, contribute to exacerbate/accelerate MN death. In particular, the role of the microglia in ALS remains unclear, partly due to the lack of experimental models that can fully recapitulate the complexity of ALS's pathology. In this study, we developed and characterized a microglial cell line, SIM-A9-expressing human mutant protein Cu[+]/Zn[+] superoxide dismutase_1 (SIM-A9hSOD1(G93A)), as a suitable model in vitro mimicking the microglia activity in ALS. The expression of hSOD1(G93A) in SIM-A9 cells induced a change in their metabolic activity, causing polarization into a pro-inflammatory phenotype and enhancing reactive oxygen species production, which is known to activate cell death processes and apoptosis. Afterward, we used our microglial model as an experimental set-up to investigate the therapeutic action of extracellular vesicles isolated from adipose mesenchymal stem cells (ASC-EVs). ASC-EVs represent a promising therapeutic treatment for ALS due to their neuroprotective and immunomodulatory properties. Here, we demonstrated that treatment with ASC-EVs is able to modulate activated ALS microglia, reducing their metabolic activity and polarizing their phenotype toward an anti-inflammatory one through a mechanism of reduction of reactive oxygen species.}, } @article {pmid38891791, year = {2024}, author = {Tokuda, E and Sakashita, Y and Tokoro, N and Date, A and Kosuge, Y and Miyasaka, T}, title = {MS785-MS27 Reactive Misfolded/Non-Native Zn-Deficient SOD1 Species Exhibit Cytotoxicity and Adopt Heterozygous Conformations in Motor Neurons.}, journal = {International journal of molecular sciences}, volume = {25}, number = {11}, pages = {}, pmid = {38891791}, issn = {1422-0067}, support = {2022-2025//The Takeda Science Foundation/ ; }, mesh = {Animals ; *Superoxide Dismutase-1/genetics/metabolism/chemistry ; *Motor Neurons/metabolism/pathology ; Mice ; *Zinc/metabolism/deficiency ; *Protein Folding ; *Amyotrophic Lateral Sclerosis/metabolism/genetics/pathology ; Humans ; Mutation ; Mice, Transgenic ; Heterozygote ; Protein Conformation ; }, abstract = {Misfolding of superoxide dismutase-1 (SOD1) is a pathological hallmark of amyotrophic lateral sclerosis (ALS) with SOD1 mutations. The development of antibodies specific for misfolded SOD1 deepens our understanding of how the protein participates in ALS pathogenesis. Since the term "misfolding" refers to various disordered conformers other than the natively folded one, which misfolded species are recognized by specific antibodies should be determined. Here, we molecularly characterized the recognition by MS785-MS27, an antibody cocktail experimentally confirmed to recognize over 100 ALS-linked SOD1 mutants. Indirect ELISA revealed that the antibody cocktail recognized Zn-deficient wild-type and mutated SOD1 species. It also recognized conformation-disordered wild-type and mutated SOD1 species, such as unfolded and oligomeric forms, but had less affinity for the aggregated form. Antibody-reactive SOD1 exhibited cytotoxicity to a motor neuron cell model, which was blocked by Zn treatment with Zn-deficient SOD1. Immunohistochemistry revealed antibody-reactive SOD1 mainly in spinal motor neurons of SOD1[G93A] mice throughout the disease course, and the distribution after symptomatic stages differed from that of other misfolded SOD1 species. This suggests that misfolded/non-native SOD1 species exist as heterogeneous populations. In conclusion, MS785-MS27 recognizes various conformation-disordered SOD1 species lacking the Zn ion.}, } @article {pmid38891774, year = {2024}, author = {Arnold, FJ and Putka, AF and Raychaudhuri, U and Hsu, S and Bedlack, RS and Bennett, CL and La Spada, AR}, title = {Revisiting Glutamate Excitotoxicity in Amyotrophic Lateral Sclerosis and Age-Related Neurodegeneration.}, journal = {International journal of molecular sciences}, volume = {25}, number = {11}, pages = {}, pmid = {38891774}, issn = {1422-0067}, mesh = {*Amyotrophic Lateral Sclerosis/metabolism/pathology ; Humans ; *Glutamic Acid/metabolism ; Animals ; Motor Neurons/metabolism/pathology ; Aging/metabolism ; Receptors, AMPA/metabolism ; Endoplasmic Reticulum Stress ; Mitochondria/metabolism ; Excitatory Amino Acid Transporter 2/metabolism ; Astrocytes/metabolism ; Reactive Oxygen Species/metabolism ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disorder. While there are five FDA-approved drugs for treating this disease, each has only modest benefits. To design new and more effective therapies for ALS, particularly for sporadic ALS of unknown and diverse etiologies, we must identify key, convergent mechanisms of disease pathogenesis. This review focuses on the origin and effects of glutamate-mediated excitotoxicity in ALS (the cortical hyperexcitability hypothesis), in which increased glutamatergic signaling causes motor neurons to become hyperexcitable and eventually die. We characterize both primary and secondary contributions to excitotoxicity, referring to processes taking place at the synapse and within the cell, respectively. 'Primary pathways' include upregulation of calcium-permeable AMPA receptors, dysfunction of the EAAT2 astrocytic glutamate transporter, increased release of glutamate from the presynaptic terminal, and reduced inhibition by cortical interneurons-all of which have been observed in ALS patients and model systems. 'Secondary pathways' include changes to mitochondrial morphology and function, increased production of reactive oxygen species, and endoplasmic reticulum (ER) stress. By identifying key targets in the excitotoxicity cascade, we emphasize the importance of this pathway in the pathogenesis of ALS and suggest that intervening in this pathway could be effective for developing therapies for this disease.}, } @article {pmid38891289, year = {2024}, author = {Idziak, R and Waligóra, H and Majchrzak, L and Szulc, P}, title = {Multifunctional Adjuvants Affect Sulfonylureas with Synthetic Auxin Mixture in Weed and Maize Grain Yield.}, journal = {Plants (Basel, Switzerland)}, volume = {13}, number = {11}, pages = {}, pmid = {38891289}, issn = {2223-7747}, abstract = {A field study in the years 2017-2019 was carried out to evaluate the impact of novel adjuvant formulations on the efficacy of sulfonylurea and synthetic auxin herbicides. Treatments included nicosulfuron + rimsulfuron + dicamba (N+R+D) at full and reduced rates with three multicomponent (TEST-1, TEST-2, TEST-3) as well as standard (MSO, S) adjuvants. In this greenhouse study, Echinochloa crus-galli seeds were planted and treated with N+R+D at 2-3 leaf stages. The water with the desired pH (4, 7, and 9) for the preparation of the spray liquid was prepared by incorporating citric acid or K3PO4 to either lower or raise the pH of the water. Adjuvant TEST-1 added to the spray liquid at pH 4 increased the effectiveness to 68%, TEST-2 to 81%, and TEST-3 to 80%, compared to 73% and 66% with the MSO and S. The efficacy of N+R+D at pH 7 with TEST-1 increased to 83%, TEST-2 to 82%, and TEST-3 to 77%, but with MSO, it increased to 81%, and 71% with S. Adjuvants TEST-1, TEST-2, and TEST-3 in the liquid at pH 9 increased efficacy to 76 and 80%, compared to 79 and 63% with MSO or S adjuvants. N+R+D applied with TEST-1, TEST-2, and TEST-3 provided greater weed control than herbicides with surfactant (S) and similar or even better than with standard methylated seed oil (MSO) adjuvants. Maize grain yield after herbicide-with-tested-adjuvant application was higher than from an untreated check, and comparable to yield from herbicide-with-MSO treatment, but higher than from S treatment.}, } @article {pmid38891112, year = {2024}, author = {Santos, JR and Park, J}, title = {MATR3's Role beyond the Nuclear Matrix: From Gene Regulation to Its Implications in Amyotrophic Lateral Sclerosis and Other Diseases.}, journal = {Cells}, volume = {13}, number = {11}, pages = {}, pmid = {38891112}, issn = {2073-4409}, support = {n/a//Canada Research Chairs/ ; 202104PJT-462444-NSB-CEAB-275899//CIHR/Canada ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology ; *Nuclear Matrix-Associated Proteins/metabolism/genetics ; *Gene Expression Regulation ; *Nuclear Matrix/metabolism ; Animals ; RNA-Binding Proteins/metabolism/genetics ; }, abstract = {Matrin-3 (MATR3) was initially discovered as a component of the nuclear matrix about thirty years ago. Since then, accumulating studies have provided evidence that MATR3 not only plays a structural role in the nucleus, but that it is also an active protein involved in regulating gene expression at multiple levels, including chromatin organization, DNA transcription, RNA metabolism, and protein translation in the nucleus and cytoplasm. Furthermore, MATR3 may play a critical role in various cellular processes, including DNA damage response, cell proliferation, differentiation, and survival. In addition to the revelation of its biological role, recent studies have reported MATR3's involvement in the context of various diseases, including neurodegenerative and neurodevelopmental diseases, as well as cancer. Moreover, sequencing studies of patients revealed a handful of disease-associated mutations in MATR3 linked to amyotrophic lateral sclerosis (ALS), which further elevated the gene's importance as a topic of study. In this review, we synthesize the current knowledge regarding the diverse functions of MATR3 in DNA- and RNA-related processes, as well as its involvement in various diseases, with a particular emphasis on ALS.}, } @article {pmid38891099, year = {2024}, author = {Hernan-Godoy, M and Rouaux, C}, title = {From Environment to Gene Expression: Epigenetic Methylations and One-Carbon Metabolism in Amyotrophic Lateral Sclerosis.}, journal = {Cells}, volume = {13}, number = {11}, pages = {}, pmid = {38891099}, issn = {2073-4409}, support = {ANR-21-CE16-0024//Agence Nationale de la Recherche/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/genetics/metabolism ; Humans ; *Epigenesis, Genetic ; *DNA Methylation/genetics ; *Carbon/metabolism ; Animals ; }, abstract = {The etiology of the neurodegenerative disease amyotrophic lateral sclerosis (ALS) is complex and considered multifactorial. The majority of ALS cases are sporadic, but familial cases also exist. Estimates of heritability range from 8% to 61%, indicating that additional factors beyond genetics likely contribute to ALS. Numerous environmental factors are considered, which may add up and synergize throughout an individual's lifetime building its unique exposome. One level of integration between genetic and environmental factors is epigenetics, which results in alterations in gene expression without modification of the genome sequence. Methylation reactions, targeting DNA or histones, represent a large proportion of epigenetic regulations and strongly depend on the availability of methyl donors provided by the ubiquitous one-carbon (1C) metabolism. Thus, understanding the interplay between exposome, 1C metabolism, and epigenetic modifications will likely contribute to elucidating the mechanisms underlying altered gene expression related to ALS and to developing targeted therapeutic interventions. Here, we review evidence for 1C metabolism alterations and epigenetic methylation dysregulations in ALS, with a focus on the impairments reported in neural tissues, and discuss these environmentally driven mechanisms as the consequences of cumulative exposome or late environmental hits, but also as the possible result of early developmental defects.}, } @article {pmid38891059, year = {2024}, author = {Dashtmian, AR and Darvishi, FB and Arnold, WD}, title = {Chronological and Biological Aging in Amyotrophic Lateral Sclerosis and the Potential of Senolytic Therapies.}, journal = {Cells}, volume = {13}, number = {11}, pages = {}, pmid = {38891059}, issn = {2073-4409}, support = {1R01AG067758, R01AG078129, and R01AG067758-02S2//national institute of health/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/genetics/pathology/metabolism/therapy ; Humans ; *Aging/pathology ; Senotherapeutics/pharmacology/therapeutic use ; Animals ; Cellular Senescence ; Mitochondria/metabolism/pathology ; DNA Damage ; }, abstract = {Amyotrophic Lateral Sclerosis (ALS) is a group of sporadic and genetic neurodegenerative disorders that result in losses of upper and lower motor neurons. Treatment of ALS is limited, and survival is 2-5 years after disease onset. While ALS can occur in younger individuals, the risk significantly increases with advancing age. Notably, both sporadic and genetic forms of ALS share pathophysiological features overlapping hallmarks of aging including genome instability/DNA damage, mitochondrial dysfunction, inflammation, proteostasis, and cellular senescence. This review explores chronological and biological aging in the context of ALS onset and progression. Age-related muscle weakness and motor unit loss mirror aspects of ALS pathology and coincide with peak ALS incidence, suggesting a potential link between aging and disease development. Hallmarks of biological aging, including DNA damage, mitochondrial dysfunction, and cellular senescence, are implicated in both aging and ALS, offering insights into shared mechanisms underlying disease pathogenesis. Furthermore, senescence-associated secretory phenotype and senolytic treatments emerge as promising avenues for ALS intervention, with the potential to mitigate neuroinflammation and modify disease progression.}, } @article {pmid38891021, year = {2024}, author = {Nguyen, L}, title = {Updates on Disease Mechanisms and Therapeutics for Amyotrophic Lateral Sclerosis.}, journal = {Cells}, volume = {13}, number = {11}, pages = {}, pmid = {38891021}, issn = {2073-4409}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/therapy/pathology/drug therapy ; Animals ; C9orf72 Protein/genetics ; }, abstract = {Amyotrophic lateral sclerosis (ALS), or Lou Gehrig's disease, is a motor neuron disease. In ALS, upper and lower motor neurons in the brain and spinal cord progressively degenerate during the course of the disease, leading to the loss of the voluntary movement of the arms and legs. Since its first description in 1869 by a French neurologist Jean-Martin Charcot, the scientific discoveries on ALS have increased our understanding of ALS genetics, pathology and mechanisms and provided novel therapeutic strategies. The goal of this review article is to provide a comprehensive summary of the recent findings on ALS mechanisms and related therapeutic strategies to the scientific audience. Several highlighted ALS research topics discussed in this article include the 2023 FDA approved drug for SOD1 ALS, the updated C9orf72 GGGGCC repeat-expansion-related mechanisms and therapeutic targets, TDP-43-mediated cryptic splicing and disease markers and diagnostic and therapeutic options offered by these recent discoveries.}, } @article {pmid38891002, year = {2024}, author = {Genchi, G and Lauria, G and Catalano, A and Carocci, A and Sinicropi, MS}, title = {Neuroprotective Effects of Curcumin in Neurodegenerative Diseases.}, journal = {Foods (Basel, Switzerland)}, volume = {13}, number = {11}, pages = {}, pmid = {38891002}, issn = {2304-8158}, abstract = {Curcumin, a hydrophobic polyphenol extracted from the rhizome of Curcuma longa, is now considered a candidate drug for the treatment of neurological diseases, including Parkinson's Disease (PD), Alzheimer's Disease (AD), Huntington's Disease (HD), Multiple Sclerosis (MS), Amyotrophic Lateral Sclerosis (ALS), and prion disease, due to its potent anti-inflammatory, antioxidant potential, anticancerous, immunomodulatory, neuroprotective, antiproliferative, and antibacterial activities. Traditionally, curcumin has been used for medicinal and dietary purposes in Asia, India, and China. However, low water solubility, poor stability in the blood, high rate of metabolism, limited bioavailability, and little capability to cross the blood-brain barrier (BBB) have limited the clinical application of curcumin, despite the important pharmacological activities of this drug. A variety of nanocarriers, including liposomes, micelles, dendrimers, cubosome nanoparticles, polymer nanoparticles, and solid lipid nanoparticles have been developed with great success to effectively deliver the active drug to brain cells. Functionalization on the surface of nanoparticles with brain-specific ligands makes them target-specific, which should significantly improve bioavailability and reduce harmful effects. The aim of this review is to summarize the studies on curcumin and/or nanoparticles containing curcumin in the most common neurodegenerative diseases, highlighting the high neuroprotective potential of this nutraceutical.}, } @article {pmid38890532, year = {2024}, author = {}, title = {Molecular pathology markers of FTD and ALS in blood extracellular vesicles.}, journal = {Nature medicine}, volume = {30}, number = {6}, pages = {1545-1546}, pmid = {38890532}, issn = {1546-170X}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/blood/genetics/pathology ; *Extracellular Vesicles/metabolism/genetics ; *Biomarkers/blood ; *Frontotemporal Dementia/genetics/blood/pathology ; Pathology, Molecular ; }, } @article {pmid38890531, year = {2024}, author = {Chatterjee, M and Özdemir, S and Fritz, C and Möbius, W and Kleineidam, L and Mandelkow, E and Biernat, J and Doğdu, C and Peters, O and Cosma, NC and Wang, X and Schneider, LS and Priller, J and Spruth, E and Kühn, AA and Krause, P and Klockgether, T and Vogt, IR and Kimmich, O and Spottke, A and Hoffmann, DC and Fliessbach, K and Miklitz, C and McCormick, C and Weydt, P and Falkenburger, B and Brandt, M and Guenther, R and Dinter, E and Wiltfang, J and Hansen, N and Bähr, M and Zerr, I and Flöel, A and Nestor, PJ and Düzel, E and Glanz, W and Incesoy, E and Bürger, K and Janowitz, D and Perneczky, R and Rauchmann, BS and Hopfner, F and Wagemann, O and Levin, J and Teipel, S and Kilimann, I and Goerss, D and Prudlo, J and Gasser, T and Brockmann, K and Mengel, D and Zimmermann, M and Synofzik, M and Wilke, C and Selma-González, J and Turon-Sans, J and Santos-Santos, MA and Alcolea, D and Rubio-Guerra, S and Fortea, J and Carbayo, Á and Lleó, A and Rojas-García, R and Illán-Gala, I and Wagner, M and Frommann, I and Roeske, S and Bertram, L and Heneka, MT and Brosseron, F and Ramirez, A and Schmid, M and Beschorner, R and Halle, A and Herms, J and Neumann, M and Barthélemy, NR and Bateman, RJ and Rizzu, P and Heutink, P and Dols-Icardo, O and Höglinger, G and Hermann, A and Schneider, A}, title = {Plasma extracellular vesicle tau and TDP-43 as diagnostic biomarkers in FTD and ALS.}, journal = {Nature medicine}, volume = {30}, number = {6}, pages = {1771-1783}, pmid = {38890531}, issn = {1546-170X}, support = {P30 AG066614/AG/NIA NIH HHS/United States ; R01 AG080470/AG/NIA NIH HHS/United States ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/blood/diagnosis/pathology/genetics ; *tau Proteins/blood/metabolism ; *Extracellular Vesicles/metabolism ; *Frontotemporal Dementia/blood/diagnosis/genetics/pathology ; *Biomarkers/blood ; *DNA-Binding Proteins/blood/genetics ; Female ; Male ; Aged ; Middle Aged ; Supranuclear Palsy, Progressive/blood/diagnosis ; Protein Isoforms/blood ; }, abstract = {Minimally invasive biomarkers are urgently needed to detect molecular pathology in frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). Here, we show that plasma extracellular vesicles (EVs) contain quantifiable amounts of TDP-43 and full-length tau, which allow the quantification of 3-repeat (3R) and 4-repeat (4R) tau isoforms. Plasma EV TDP-43 levels and EV 3R/4R tau ratios were determined in a cohort of 704 patients, including 37 genetically and 31 neuropathologically proven cases. Diagnostic groups comprised patients with TDP-43 proteinopathy ALS, 4R tauopathy progressive supranuclear palsy, behavior variant FTD (bvFTD) as a group with either tau or TDP-43 pathology, and healthy controls. EV tau ratios were low in progressive supranuclear palsy and high in bvFTD with tau pathology. EV TDP-43 levels were high in ALS and in bvFTD with TDP-43 pathology. Both markers discriminated between the diagnostic groups with area under the curve values >0.9, and between TDP-43 and tau pathology in bvFTD. Both markers strongly correlated with neurodegeneration, and clinical and neuropsychological markers of disease severity. Findings were replicated in an independent validation cohort of 292 patients including 34 genetically confirmed cases. Taken together, the combination of EV TDP-43 levels and EV 3R/4R tau ratios may aid the molecular diagnosis of FTD, FTD spectrum disorders and ALS, providing a potential biomarker to monitor disease progression and target engagement in clinical trials.}, } @article {pmid38890465, year = {2024}, author = {Brown, AL and Wilkins, OG and Keuss, MJ and Kargbo-Hill, SE and Zanovello, M and Lee, WC and Bampton, A and Lee, FCY and Masino, L and Qi, YA and Bryce-Smith, S and Gatt, A and Hallegger, M and Fagegaltier, D and Phatnani, H and , and Newcombe, J and Gustavsson, EK and Seddighi, S and Reyes, JF and Coon, SL and Ramos, D and Schiavo, G and Fisher, EMC and Raj, T and Secrier, M and Lashley, T and Ule, J and Buratti, E and Humphrey, J and Ward, ME and Fratta, P}, title = {Author Correction: TDP-43 loss and ALS-risk SNPs drive mis-splicing and depletion of UNC13A.}, journal = {Nature}, volume = {631}, number = {8020}, pages = {E7}, doi = {10.1038/s41586-024-07577-9}, pmid = {38890465}, issn = {1476-4687}, support = {P30 AG066514/AG/NIA NIH HHS/United States ; }, } @article {pmid38889636, year = {2024}, author = {Alkhazaali-Ali, Z and Sahab-Negah, S and Boroumand, AR and Tavakol-Afshari, J}, title = {MicroRNA (miRNA) as a biomarker for diagnosis, prognosis, and therapeutics molecules in neurodegenerative disease.}, journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie}, volume = {177}, number = {}, pages = {116899}, doi = {10.1016/j.biopha.2024.116899}, pmid = {38889636}, issn = {1950-6007}, mesh = {Humans ; *MicroRNAs/genetics ; *Neurodegenerative Diseases/diagnosis/genetics/therapy ; *Biomarkers/metabolism ; Animals ; Prognosis ; }, abstract = {Neurodegenerative diseases that include Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), Huntington's disease (HD), and multiple sclerosis (MS) that arise due to numerous causes like protein accumulation and autoimmunity characterized by neurologic depletion which lead to incapacity in normal physiological function such as thinking and movement in these patients. Glial cells perform an important role in protective neuronal function; in the case of neuroinflammation, glial cell dysfunction can promote the development of neurodegenerative diseases. miRNA that participates in gene regulation and plays a vital role in many biological processes in the body; in the central nervous system (CNS), it can play an essential part in neural maturation and differentiation. In neurodegenerative diseases, miRNA dysregulation occurs, enhancing the development of these diseases. In this review, we discuss neurodegenerative disease (Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS)) and how miRNA is preserved as a diagnostic biomarker or therapeutic agent in these disorders. Finally, we highlight miRNA as therapy.}, } @article {pmid38889523, year = {2024}, author = {Müller, HP and Abrahao, A and Beaulieu, C and Benatar, M and Dionne, A and Genge, A and Frayne, R and Graham, SJ and Gibson, S and Korngut, L and Luk, C and Welsh, RC and Zinman, L and Kassubek, J and Kalra, S}, title = {Temporal and spatial progression of microstructural cerebral degeneration in ALS: A multicentre longitudinal diffusion tensor imaging study.}, journal = {NeuroImage. Clinical}, volume = {43}, number = {}, pages = {103633}, pmid = {38889523}, issn = {2213-1582}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnostic imaging/pathology ; Male ; Female ; Middle Aged ; *Disease Progression ; *Diffusion Tensor Imaging/methods ; Longitudinal Studies ; Aged ; *Pyramidal Tracts/diagnostic imaging/pathology ; Adult ; Cross-Sectional Studies ; Anisotropy ; Prospective Studies ; }, abstract = {OBJECTIVE: The corticospinal tract (CST) reveals progressive microstructural alterations in ALS measurable by DTI. The aim of this study was to evaluate fractional anisotropy (FA) along the CST as a longitudinal marker of disease progression in ALS.

METHODS: The study cohort consisted of 114 patients with ALS and 110 healthy controls from the second prospective, longitudinal, multicentre study of the Canadian ALS Neuroimaging Consortium (CALSNIC-2). DTI and clinical data from a harmonized protocol across 7 centres were collected. Thirty-nine ALS patients and 61 controls completed baseline and two follow-up visits and were included for longitudinal analyses. Whole brain-based spatial statistics and hypothesis-guided tract-of-interest analyses were performed for cross-sectional and longitudinal analyses.

RESULTS: FA was reduced at baseline and longitudinally in the CST, mid-corpus callosum (CC), frontal lobe, and other ALS-related tracts, with alterations most evident in the CST and mid-CC. CST and pontine FA correlated with functional impairment (ALSFRS-R), upper motor neuron function, and clinical disease progression rate. Reduction in FA was largely located in the upper CST; however, the longitudinal decline was greatest in the lower CST. Effect sizes were dependent on region, resulting in study group sizes between 17 and 31 per group over a 9-month interval. Cross-sectional effect sizes were maximal in the upper CST; whereas, longitudinal effect sizes were maximal in mid-callosal tracts.

CONCLUSIONS: Progressive microstructural alterations in ALS are most prominent in the CST and CC. DTI can provide a biomarker of cerebral degeneration in ALS, with longitudinal changes in white matter demonstrable over a reasonable observation period, with a feasible number of participants, and within a multicentre framework.}, } @article {pmid38889403, year = {2024}, author = {Zhu, Y and Wang, F and Xia, Y and Wang, L and Lin, H and Zhong, T and Wang, X}, title = {Research progress on astrocyte-derived extracellular vesicles in the pathogenesis and treatment of neurodegenerative diseases.}, journal = {Reviews in the neurosciences}, volume = {35}, number = {8}, pages = {855-875}, pmid = {38889403}, issn = {2191-0200}, mesh = {Humans ; *Extracellular Vesicles/metabolism ; *Neurodegenerative Diseases/metabolism/therapy ; *Astrocytes/metabolism ; Animals ; Cell Communication/physiology ; }, abstract = {Neurodegenerative disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD), pose significant global health risks and represent a substantial public health concern in the contemporary era. A primary factor in the pathophysiology of these disorders is aberrant accumulation and aggregation of pathogenic proteins within the brain and spinal cord. Recent investigations have identified extracellular vesicles (EVs) in the central nervous system (CNS) as potential carriers for intercellular transport of misfolded proteins associated with neurodegenerative diseases. EVs are involved in pathological processes that contribute to various brain disorders including neurodegenerative disorders. Proteins linked to neurodegenerative disorders are secreted and distributed from cell to cell via EVs, serving as a mechanism for direct intercellular communication through the transfer of biomolecules. Astrocytes, as active participants in CNS intercellular communication, release astrocyte-derived extracellular vesicles (ADEVs) that are capable of interacting with diverse target cells. This review primarily focuses on the involvement of ADEVs in the development of neurological disorders and explores their potential dual roles - both advantageous and disadvantageous in the context of neurological disorders. Furthermore, this review examines the current studies investigating ADEVs as potential biomarkers for the diagnosis and treatment of neurodegenerative diseases. The prospects and challenges associated with the application of ADEVs in clinical settings were also comprehensively reviewed.}, } @article {pmid38888068, year = {2024}, author = {Shefner, JM and Cudkowicz, ME}, title = {Failures to Replicate: What Recent Negative Phase 3 Trials Have Taught Us about Amyotrophic Lateral Sclerosis Clinical Research.}, journal = {Annals of neurology}, volume = {96}, number = {2}, pages = {211-215}, doi = {10.1002/ana.26999}, pmid = {38888068}, issn = {1531-8249}, mesh = {*Amyotrophic Lateral Sclerosis/therapy ; Humans ; *Clinical Trials, Phase III as Topic/methods ; Biomedical Research ; }, } @article {pmid38887944, year = {2024}, author = {Mendes, AE and Silva, GD and Jorge, FMH and Callegaro, D}, title = {Tongue pressure is a strong predictor of recommendation for gastrostomy in amyotrophic lateral sclerosis.}, journal = {Muscle & nerve}, volume = {70}, number = {3}, pages = {409-412}, doi = {10.1002/mus.28174}, pmid = {38887944}, issn = {1097-4598}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology/therapy ; *Gastrostomy ; Female ; Male ; Middle Aged ; Aged ; Prospective Studies ; *Tongue/physiopathology ; Pressure ; ROC Curve ; Follow-Up Studies ; }, abstract = {INTRODUCTION/AIMS: Objective and practical biomarkers to determine the need for gastrostomy in patients with amyotrophic lateral sclerosis (ALS) are lacking. Tongue pressure (TP) is a promising biomarker because it is associated with bulbar dysfunction. The aims of this study were to evaluate the association of TP with the need for gastrostomy, and to determine its optimal cut-off value.

METHODS: This prospective observational study included participants with ALS taking nutrition orally. TP was evaluated using the Iowa Oral Performance Instrument. Need for gastrostomy as determined by a multidisciplinary team during a 12-month follow up period was recorded. Associations between TP and need for gastrostomy placement were performed. ROC curve analysis determined the optimal cut-off value of TP to predict gastrostomy.

RESULTS: Of 208 screened participants, 119 were included. Gastrostomy was indicated in 45% (53), in a 12-month follow up period. TP of ≤20 kPA was a strong predictor of gastrostomy indication (OR 11.8, CI 95% [4.61, 34.7], p < .001). The association persisted even after adjustment for weight loss, pneumonia, prolonged feeding duration, Revised ALS Functional Rating Scale score, and American Speech-Language-Hearing Association scale score (OR 4.51, CI 95% [1.50, 14.9], p = .009). By receiver operating characteristic curve analysis, 20 kPA represented the optimal cut-off value (sensitivity 0.75, specificity 0.89).

DISCUSSION: TP is a strong independent predictor of gastrostomy indication in the subsequent 12 months in patients with ALS, with good sensitivity and specificity at a cutoff value of ≤20 kPA, suggesting that it may be a promising biomarker in clinical practice.}, } @article {pmid38887384, year = {2024}, author = {Tang, X and Li, Q and Huang, G and Chen, Z and Huang, Y and Pei, X and Zhao, S and Liu, Z and Guo, T and Liang, F}, title = {Immediate Efficacy of Contralateral Acupuncture on SI3 Combined with Active Exercise for Acute Lumbar Sprains: Protocol for a Randomized Controlled Trial.}, journal = {Journal of pain research}, volume = {17}, number = {}, pages = {2099-2110}, pmid = {38887384}, issn = {1178-7090}, abstract = {PURPOSE: Acute lumbar sprain (ALS) is a common clinical disease characterized by persistent intolerable low back pain and limitation of movement, and quick pain relief and restoration of mobility in a short time are the main needs of patients when they visit the clinic. This study aims to evaluate the immediate efficacy of contralateral acupuncture (CAT) on SI3 combined with active exercise in treating ALS.

METHODS AND ANALYSIS: This study is a randomized controlled trial which will recruit 118 eligible participants aged 18 to 55 years with ALS at the Second Affiliated Hospital of Yunnan University of Chinese Medicine between March 2024 and December 2026. Participants will be randomly assigned to the acupuncture group or the sham-acupuncture group in a 1:1 ratio. The acupuncture group will receive a 10-minute acupuncture treatment combined with active exercise, while the sham-acupuncture group will receive a 10-minute sham acupuncture treatment combined with active exercise. Randomization will use a computer-generated sequence with allocation concealed in opaque envelopes. The primary outcome will be the pain visual analogue scale (VAS) scores after 10 minutes of treatment. Secondary outcomes will include the pain VAS scores at other time points (2, 4, 6, and 8 minutes post-treatment), the lumbar range of motion (ROM) scores at various time points, blinded assessment, the treatment effect expectancy scale, and the rescue analgesia rate. The analysis will follow the intention-to-treat principle. The primary outcome will be analyzed using ANCOVA, and secondary outcomes with repeated measures ANOVA. The rescue analgesia rate will be assessed using either the χ[2] test or Fisher's exact test.

DISCUSSION: This study is the first randomized controlled trial to assess the immediate efficacy of CAT in combination with active exercise for ALS. This study will provide a simple, rapid, and effective treatment for the clinical management of ALS.}, } @article {pmid38887187, year = {2024}, author = {Ghaderi, S and Fatehi, F and Kalra, S and Mohammadi, S and Zemorshidi, F and Ramezani, M and Hesami, O and Pezeshgi, S and Batouli, SAH}, title = {Volume loss in the left anterior-superior subunit of the hypothalamus in amyotrophic lateral sclerosis.}, journal = {CNS neuroscience & therapeutics}, volume = {30}, number = {6}, pages = {e14801}, pmid = {38887187}, issn = {1755-5949}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnostic imaging/pathology ; Male ; Female ; Middle Aged ; *Hypothalamus/diagnostic imaging/pathology ; Aged ; *Magnetic Resonance Imaging ; Adult ; }, abstract = {BACKGROUND AND OBJECTIVE: Amyotrophic lateral sclerosis (ALS) causes motor neuron loss and progressive paralysis. While traditionally viewed as motor neuron disease (MND), ALS also affects non-motor regions, such as the hypothalamus. This study aimed to quantify the hypothalamic subregion volumes in patients with ALS versus healthy controls (HCs) and examine their associations with demographic and clinical features.

METHODS: Forty-eight participants (24 ALS patients and 24 HCs) underwent structural MRI. A deep convolutional neural network was used for the automated segmentation of the hypothalamic subunits, including the anterior-superior (a-sHyp), anterior-inferior (a-iHyp), superior tuberal (supTub), inferior tuberal (infTub), and posterior (posHyp). The neural network was validated using FreeSurfer v7.4.1, with individual head size variations normalized using total intracranial volume (TIV) normalization. Statistical analyses were performed for comparisons using independent sample t-tests. Correlations were calculated using Pearson's and Spearman's tests (p < 0.05). The standard mean difference (SMD) was used to compare the mean differences between parametric variables.

RESULTS: The volume of the left a-sHyp hypothalamic subunit was significantly lower in ALS patients than in HCs (p = 0.023, SMD = -0.681). No significant correlation was found between the volume of the hypothalamic subunits, body mass index (BMI), and ALSFRS-R in patients with ALS. However, right a-sHyp (r = 0.420, p = 0.041) was correlated with disease duration, whereas right supTub (r = -0.471, p = 0.020) and left postHyp (r = -0.406, p = 0.049) were negatively correlated with age. There was no significant difference in the volume of hypothalamic subunits between males and females, and no significant difference was found between patients with revised ALS Functional Rating Scale (ALSFRS-R) scores ≤41 and >41 and those with a disease duration of 9 months or less.

DISCUSSION AND CONCLUSION: The main finding suggests atrophy of the left a-sHyp hypothalamic subunit in patients with ALS, which is supported by previous research as an extra-motor neuroimaging finding for ALS.}, } @article {pmid38886938, year = {2025}, author = {Helmold, BR and Ahrens, A and Fitzgerald, Z and Ozdinler, PH}, title = {Spastin and alsin protein interactome analyses begin to reveal key canonical pathways and suggest novel druggable targets.}, journal = {Neural regeneration research}, volume = {20}, number = {3}, pages = {725-739}, pmid = {38886938}, issn = {1673-5374}, support = {R01 AG061708/AG/NIA NIH HHS/United States ; }, abstract = {Developing effective and long-term treatment strategies for rare and complex neurodegenerative diseases is challenging. One of the major roadblocks is the extensive heterogeneity among patients. This hinders understanding the underlying disease-causing mechanisms and building solutions that have implications for a broad spectrum of patients. One potential solution is to develop personalized medicine approaches based on strategies that target the most prevalent cellular events that are perturbed in patients. Especially in patients with a known genetic mutation, it may be possible to understand how these mutations contribute to problems that lead to neurodegeneration. Protein-protein interaction analyses offer great advantages for revealing how proteins interact, which cellular events are primarily involved in these interactions, and how they become affected when key genes are mutated in patients. This line of investigation also suggests novel druggable targets for patients with different mutations. Here, we focus on alsin and spastin, two proteins that are identified as "causative" for amyotrophic lateral sclerosis and hereditary spastic paraplegia, respectively, when mutated. Our review analyzes the protein interactome for alsin and spastin, the canonical pathways that are primarily important for each protein domain, as well as compounds that are either Food and Drug Administration-approved or are in active clinical trials concerning the affected cellular pathways. This line of research begins to pave the way for personalized medicine approaches that are desperately needed for rare neurodegenerative diseases that are complex and heterogeneous.}, } @article {pmid38886047, year = {2024}, author = {Jiang, Q and Lin, J and Wei, Q and Yang, T and Hou, Y and Zhang, L and Ou, R and Xiao, Y and Wang, S and Zheng, X and Li, C and Shang, H}, title = {Amyotrophic lateral sclerosis patients with various gene mutations show diverse motor phenotypes and survival in China.}, journal = {Journal of medical genetics}, volume = {61}, number = {9}, pages = {839-846}, doi = {10.1136/jmg-2024-109909}, pmid = {38886047}, issn = {1468-6244}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/mortality/pathology ; Male ; Female ; *C9orf72 Protein/genetics ; *Mutation ; Middle Aged ; *Phenotype ; China/epidemiology ; *Superoxide Dismutase-1/genetics ; Adult ; *Genetic Association Studies/methods ; RNA-Binding Protein FUS/genetics ; DNA-Binding Proteins/genetics ; Aged ; Genotype ; Age of Onset ; Genetic Predisposition to Disease ; Proteins/genetics ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder characterised by progressive degeneration of motor neurons. Genetic factors have a substantial impact on ALS. Therefore, this study aimed to explore the correlation between genotype (SOD1, TARDBP, FUS, C9orf72) and phenotype in ALS.

METHODS: Genetic analysis was performed on 2038 patients with ALS, among which 1696 patients with sporadic ALS (SALS) as controls for genotype-phenotype analysis, and 1602 SALS as controls for survival analysis. Logistic regression and Cox proportional hazards models were used for statistical analysis.

RESULTS: A total of 172 patients with ALS with the gene mutations were included in the statistical analysis (SOD1, n=65; FUS, n=43; TARDBP, n=27; C9orf72, n=37). SOD1 mutations were more frequent in flail leg phenotype (OR 7.317, p=0.001) and less in bulbar phenotype (OR 0.222, p=0.038). C9orf72 expansions exhibited higher frequency in bulbar phenotype (OR 2.770, p=0.008). SOD1 and FUS mutations were significantly associated with earlier age of onset (HR 2.039, p<0.001; HR 1.762, p=0.001). The patients with SOD1 mutations, C9orf72 expansions and those carrying pathogenic FUS mutations had significantly increased death risk (HR 2.217, p<0.001; HR 1.694, p=0.008; HR 1.652, p=0.036). The increased risk of death in ALS with C9orf72 expansions was significant in females (HR 2.419, p=0.014) but not in males (HR 1.442, p=0.128).

CONCLUSION: Our study revealed distinct motor phenotypic tendencies in patients with ALS with different genotypes, indicating variations in the vulnerability of motor neurons during the disease's progression. Furthermore, we made novel discoveries regarding survival of different gene mutations, warranting further investigation.}, } @article {pmid38885838, year = {2024}, author = {López Sanz, P and Azaña Defez, JM}, title = {Is ILVEN a misnomer? Proposal of MALID as an accurate nomenclature. Response to Polubothu et al's "ILVEN should be genotyped to direct treatment and genetic counselling".}, journal = {Journal of the American Academy of Dermatology}, volume = {91}, number = {4}, pages = {e107-e108}, doi = {10.1016/j.jaad.2024.05.084}, pmid = {38885838}, issn = {1097-6787}, mesh = {Humans ; *Terminology as Topic ; *Genetic Counseling ; Genotype ; }, } @article {pmid38884646, year = {2024}, author = {Mielke, JK and Klingeborn, M and Schultz, EP and Markham, EL and Reese, ED and Alam, P and Mackenzie, IR and Ly, CV and Caughey, B and Cashman, NR and Leavens, MJ}, title = {Seeding activity of human superoxide dismutase 1 aggregates in familial and sporadic amyotrophic lateral sclerosis postmortem neural tissues by real-time quaking-induced conversion.}, journal = {Acta neuropathologica}, volume = {147}, number = {1}, pages = {100}, pmid = {38884646}, issn = {1432-0533}, support = {5P30GM140963-03/GM/NIGMS NIH HHS/United States ; P20 GM152335/GM/NIGMS NIH HHS/United States ; Sloan Scholars Mentoring Network Seed Grant//Alfred P. Sloan Foundation/ ; R21 EY033057/EY/NEI NIH HHS/United States ; P30 GM140963/GM/NIGMS NIH HHS/United States ; R01 NS138499/NS/NINDS NIH HHS/United States ; 1P20GM152335-01/GM/NIGMS NIH HHS/United States ; }, mesh = {Aged ; Female ; Humans ; Male ; Middle Aged ; *Amyotrophic Lateral Sclerosis/genetics/pathology/metabolism ; C9orf72 Protein/genetics ; Motor Cortex/pathology/metabolism ; Mutation/genetics ; *Spinal Cord/pathology/metabolism ; *Superoxide Dismutase-1/genetics/metabolism ; *Biomarkers/analysis ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative disease with average lifespan of 2-5 years after diagnosis. The identification of novel prognostic and pharmacodynamic biomarkers are needed to facilitate therapeutic development. Metalloprotein human superoxide dismutase 1 (SOD1) is known to accumulate and form aggregates in patient neural tissue with familial ALS linked to mutations in their SOD1 gene. Aggregates of SOD1 have also been detected in other forms of ALS, including the sporadic form and the most common familial form linked to abnormal hexanucleotide repeat expansions in the Chromosome 9 open reading frame 72 (C9ORF72) gene. Here, we report the development of a real-time quaking-induced conversion (RT-QuIC) seed amplification assay using a recombinant human SOD1 substrate to measure SOD1 seeding activity in postmortem spinal cord and motor cortex tissue from persons with different ALS etiologies. Our SOD1 RT-QuIC assay detected SOD1 seeds in motor cortex and spinal cord dilutions down to 10[-5]. Importantly, we detected SOD1 seeding activity in specimens from both sporadic and familial ALS cases, with the latter having mutations in either their SOD1 or C9ORF72 genes. Analyses of RT-QuIC parameters indicated similar lag phases in spinal cords of sporadic and familial ALS patients, but higher ThT fluorescence maxima by SOD1 familial ALS specimens and sporadic ALS thoracic cord specimens. For a subset of sporadic ALS patients, motor cortex and spinal cords were examined, with seeding activity in both anatomical regions. Our results suggest SOD1 seeds are in ALS patient neural tissues not linked to SOD1 mutation, suggesting that SOD1 seeding activity may be a promising biomarker, particularly in sporadic ALS cases for whom genetic testing is uninformative.}, } @article {pmid38884572, year = {2024}, author = {Benkirane, M and Bonhomme, M and Morsy, H and Safgren, SL and Marelli, C and Chaussenot, A and Smedley, D and Cipriani, V and de Sainte-Agathe, JM and Ding, C and Larrieu, L and Vestito, L and Margot, H and Lesca, G and Ramond, F and Castrioto, A and Baux, D and Verheijen, J and Sansa, E and Giunti, P and Haetty, A and Bergougnoux, A and Pointaux, M and Ardouin, O and Van Goethem, C and Vincent, MC and Hadjivassiliou, M and Cossée, M and Rouaud, T and Bartsch, O and Freeman, WD and Wierenga, KJ and Klee, EW and Vandrovcova, J and Houlden, H and Debant, A and Koenig, M}, title = {De novo and inherited monoallelic variants in TUBA4A cause ataxia and spasticity.}, journal = {Brain : a journal of neurology}, volume = {147}, number = {11}, pages = {3681-3689}, doi = {10.1093/brain/awae193}, pmid = {38884572}, issn = {1460-2156}, support = {//Connaître les Syndromes Cérébelleux/ ; }, mesh = {Humans ; *Tubulin/genetics ; Male ; Female ; Middle Aged ; *Muscle Spasticity/genetics ; *Mutation, Missense/genetics ; Adult ; Aged ; Cerebellar Ataxia/genetics ; Spinocerebellar Ataxias/genetics ; Pedigree ; Cohort Studies ; France ; Intellectual Disability ; Optic Atrophy ; }, abstract = {Alpha-tubulin 4A encoding gene (TUBA4A) has been associated with familial amyotrophic lateral sclerosis and frontotemporal dementia, based on identification of likely pathogenic variants in patients from distinct amyotrophic lateral sclerosis and frontotemporal dementia cohorts. By screening a multicentric French cohort of 448 unrelated probands presenting with cerebellar ataxia, we identified ultra-rare TUBA4A missense variants, all being absent from public databases and predicted pathogenic by multiple in silico tools. In addition, gene burden analyses in the 100 000 Genomes project (100KGP) showed enrichment of TUBA4A rare variants in the inherited ataxia group compared to controls [odds ratio: 57.0847 (10.2-576.7); P = 4.02 ×10-7]. Taken together, we report 12 patients presenting with spasticity and/or cerebellar ataxia and harbouring a predicted pathogenic TUBA4A missense mutation, including five confirmed de novo cases and a mutation previously reported in a large family presenting with spastic ataxia. Cultured fibroblasts from three patients harbouring distinct TUBA4A missense showed significant alterations in microtubule organization and dynamics, providing insight of TUBA4A variants pathogenicity. Our data confirm the identification of a hereditary spastic ataxia disease gene with variable age of onset, expanding the clinical spectrum of TUBA4A associated phenotypes.}, } @article {pmid38883980, year = {2024}, author = {Azam, HMH and Rößling, RI and Geithe, C and Khan, MM and Dinter, F and Hanack, K and Prüß, H and Husse, B and Roggenbuck, D and Schierack, P and Rödiger, S}, title = {MicroRNA biomarkers as next-generation diagnostic tools for neurodegenerative diseases: a comprehensive review.}, journal = {Frontiers in molecular neuroscience}, volume = {17}, number = {}, pages = {1386735}, pmid = {38883980}, issn = {1662-5099}, abstract = {Neurodegenerative diseases (NDs) are characterized by abnormalities within neurons of the brain or spinal cord that gradually lose function, eventually leading to cell death. Upon examination of affected tissue, pathological changes reveal a loss of synapses, misfolded proteins, and activation of immune cells-all indicative of disease progression-before severe clinical symptoms become apparent. Early detection of NDs is crucial for potentially administering targeted medications that may delay disease advancement. Given their complex pathophysiological features and diverse clinical symptoms, there is a pressing need for sensitive and effective diagnostic methods for NDs. Biomarkers such as microRNAs (miRNAs) have been identified as potential tools for detecting these diseases. We explore the pivotal role of miRNAs in the context of NDs, focusing on Alzheimer's disease, Parkinson's disease, Multiple sclerosis, Huntington's disease, and Amyotrophic Lateral Sclerosis. The review delves into the intricate relationship between aging and NDs, highlighting structural and functional alterations in the aging brain and their implications for disease development. It elucidates how miRNAs and RNA-binding proteins are implicated in the pathogenesis of NDs and underscores the importance of investigating their expression and function in aging. Significantly, miRNAs exert substantial influence on post-translational modifications (PTMs), impacting not just the nervous system but a wide array of tissues and cell types as well. Specific miRNAs have been found to target proteins involved in ubiquitination or de-ubiquitination processes, which play a significant role in regulating protein function and stability. We discuss the link between miRNA, PTM, and NDs. Additionally, the review discusses the significance of miRNAs as biomarkers for early disease detection, offering insights into diagnostic strategies.}, } @article {pmid38882692, year = {2024}, author = {Yang, T and Wei, Q and Li, C and Ou, R and Lin, J and Cheng, Y and Xiao, Y and Shang, H}, title = {Peripheral immunity involvement in the cognitive impairment of sporadic amyotrophic lateral sclerosis.}, journal = {Frontiers in neurology}, volume = {15}, number = {}, pages = {1405275}, pmid = {38882692}, issn = {1664-2295}, abstract = {BACKGROUND: Recent research has indicated the significance of immune activation in amyotrophic lateral sclerosis (ALS). However, the impact of peripheral immunity on cognitive impairment in sporadic ALS remains poorly characterized. Therefore, we aim to assess the relationship between peripheral immune parameters and cognitive impairment in patients with sporadic ALS.

METHODS: A case-control study involving 289 patients with sporadic ALS was conducted. All participants underwent cognitive assessment and measurements of blood immune parameters. The main outcomes included adjusted odds ratios (ORs) in multivariate logistic regression analysis and adjusted coefficients in a multivariate linear regression model. Sensitivity analysis was performed with stratification by the King's clinical stage.

RESULTS: Cognitive impairment was observed in 98 (33.9%) patients. Higher counts of leukocyte (OR, 0.53; 95% CI, 0.29 to 0.95; p = 0.03), neutrophil (OR, 0.48; 95% CI, 0.26 to 0.88; p = 0.02), and monocyte (OR, 0.33; 95% CI, 0.18 to 0.60; p < 0.001) were significantly associated with better cognitive preformence in sporadic ALS, particularly among patients in King's clinical stages 1 and 2. Conversely, a higher percentage of CD4+ T cells was linked to an increased risk of cognitive impairment (OR, 2.79; 95% CI, 1.52 to 5.09; p = 0.001), particularly evident in patients in King's clinical stage 3.

CONCLUSION: These results highlight the involvement of peripheral immunity in the cognitive impairment of sporadic ALS and suggest dynamic and intricate roles that vary across disease stages. Elucidating the links between immunity and ALS sheds light on the pathophysiological mechanisms underlying this fatal neurodegenerative disorder and informs potential immunotherapeutic strategies.}, } @article {pmid38879961, year = {2024}, author = {Milella, G and Zoccolella, S and Giugno, A and Filardi, M and D'Errico, E and Piccirilli, G and Nanni, AG and Urso, D and Nigro, S and Tafuri, B and Tamburrino, L and Gnoni, V and Logroscino, G}, title = {Mapping lower-limbs muscle vulnerability in patients with ALS: The role of upper and lower motor neurons.}, journal = {Journal of the neurological sciences}, volume = {462}, number = {}, pages = {123098}, doi = {10.1016/j.jns.2024.123098}, pmid = {38879961}, issn = {1878-5883}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology ; Male ; Female ; Middle Aged ; *Muscle, Skeletal/physiopathology ; *Motor Neurons/physiology ; Aged ; *Muscle Strength/physiology ; *Lower Extremity/physiopathology ; Muscle Weakness/physiopathology/etiology ; Adult ; Cohort Studies ; }, abstract = {BACKGROUND: Several studies have reported disproportionate wasting of the flexor muscles of the lower limbs (LL) compared to the extensors in patients with amyotrophic lateral sclerosis (ALS). However, these studies have involved small sample sizes (n 〈100), and their findings have been inconsistent. Thus, it remains uncertain whether a distinct pattern of LL muscle weakness is specific to ALS.

AIMS: To investigate the muscle weakness pattern in the LL at the knee, ankle, and toes in a large cohort of ALS patients and evaluate the relationship between the pattern of muscle strength and the extent of upper (UMN) and lower (LMN) motoneuron impairment.

MATERIAL AND METHODS: The strength of flexor and extensor muscle was evaluated in 1250 legs of newly diagnosed ALS patients at the knee, ankle, and foot toes. UMN and LMN burden were assessed using validated scores. Within-subjects ANOVA considering the type of muscle (flexor/extensor) and anatomical sites (knee/ankle/toes) and mixed-factorial ANOVA were conducted to explore the impact of UMN and LMN impairments on the muscle weakness pattern.

RESULTS: Muscle strength showed a significant decline from proximal to distal regions. Indeed both flexor and extensor muscles at the knee outperformed those at the ankle and toes. Within each site, extensor muscles exhibited less strength than flexor, except at the knee. Patients with heightened UMN impairment showed a more marked difference between flexors and extensors within each site, with extensor muscles being more compromised at the ankle and toes. Higher LMN impairment corresponded to a more pronounced weakness in flexor muscles at the ankle and toes compared to those at the knee.

CONCLUSIONS: The extensor muscle at the knee and the flexors at the foot and toes displayed relative resistance to ALS disease. UMN impairment amplified the differences between flexor and extensor muscles within each site, while LMN impairment demonstrated a clear distal-to-proximal vulnerability.}, } @article {pmid38879765, year = {2024}, author = {Sharma, A and Kakkar, A and Khanna, M and Devi, S}, title = {Arbutin's Potential in Neuroprotection: A Promising Role in Mitigating Neurodegenerative Diseases.}, journal = {Current drug research reviews}, volume = {}, number = {}, pages = {}, doi = {10.2174/0125899775298987240528050110}, pmid = {38879765}, issn = {2589-9783}, abstract = {Naturally occurring glycosylated hydroquinone Arbutin, has drawn interest due to its possible function in reducing the risk of neurodegenerative diseases such as Huntington's disease, amyotrophic lateral sclerosis, Parkinson's disease, and Alzheimer's disease. Arbutin is well-known for its anti-inflammatory and antioxidant properties, which are essential in preventing oxidative stress and neuroinflammation. Research has shown that arbutin might alter important physiological pathways connected to protein misfolding, synapse function, and neuronal survival processes linked to the development of neurodegenerative diseases. Arbutin can also penetrate the blood- -brain barrier, which increases its therapeutic potential. Arbutin's neuroprotective properties and promise as a therapeutic agent for neurodegenerative illnesses are summarized in this review, which also emphasizes the need for further study into the molecular processes behind these effects.}, } @article {pmid38879591, year = {2024}, author = {Lambert-Smith, IA and Shephard, VK and McAlary, L and Yerbury, JJ and Saunders, DN}, title = {High-content analysis of proteostasis capacity in cellular models of amyotrophic lateral sclerosis (ALS).}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {13844}, pmid = {38879591}, issn = {2045-2322}, mesh = {*Amyotrophic Lateral Sclerosis/metabolism/genetics/pathology ; *Proteostasis ; Humans ; *Superoxide Dismutase-1/metabolism/genetics ; *Protein Folding ; *Mutation ; Cell Line ; Mice ; Animals ; }, abstract = {Disrupted proteome homeostasis (proteostasis) in amyotrophic lateral sclerosis (ALS) has been a major focus of research in the past two decades. However, the proteostasis processes that become disturbed in ALS are not fully understood. Obtaining more detailed knowledge of proteostasis disruption in association with different ALS-causing mutations will improve our understanding of ALS pathophysiology and may identify novel therapeutic targets and strategies for ALS patients. Here we describe the development and use of a novel high-content analysis (HCA) assay to investigate proteostasis disturbances caused by the expression of several ALS-causing gene variants. This assay involves the use of conformationally-destabilised mutants of firefly luciferase (Fluc) to examine protein folding/re-folding capacity in NSC-34 cells expressing ALS-associated mutations in the genes encoding superoxide dismutase-1 (SOD1[A4V]) and cyclin F (CCNF[S621G]). We demonstrate that these Fluc isoforms can be used in high-throughput format to report on reductions in the activity of the chaperone network that result from the expression of SOD1[A4V], providing multiplexed information at single-cell resolution. In addition to SOD1[A4V] and CCNF[S621G], NSC-34 models of ALS-associated TDP-43, FUS, UBQLN2, OPTN, VCP and VAPB mutants were generated that could be screened using this assay in future work. For ALS-associated mutant proteins that do cause reductions in protein quality control capacity, such as SOD1[A4V], this assay has potential to be applied in drug screening studies to identify candidate compounds that can ameliorate this deficiency.}, } @article {pmid38879469, year = {2024}, author = {Dai, Z and Zhou, X}, title = {Associations between allostatic load and hepatic steatosis and liver fibrosis: evidence from NHANES 2017-2020.}, journal = {BMC public health}, volume = {24}, number = {1}, pages = {1602}, pmid = {38879469}, issn = {1471-2458}, mesh = {Humans ; Female ; Male ; *Allostasis/physiology ; Middle Aged ; *Liver Cirrhosis ; *Nutrition Surveys ; *Fatty Liver/physiopathology ; Adult ; Aged ; Cross-Sectional Studies ; Risk Factors ; }, abstract = {BACKGROUND: Allostatic load, the cumulative strain resulting from chronic stress responses, has been linked to disease occurrence and progression, yet research quantifying this relationship is limited. This study aimed to explore the relationship between allostatic load score (ALS) levels and the degree of hepatic steatosis and fibrosis.

METHODS: Data from the National Health and Nutrition Examination Survey 2017-2020 were analyzed. The ALS was based on the statistical distribution, assigning one point for each biomarker if it was in the highest risk quartile, and then summing them to generate the ALS score (range, 0-8). The multivariate linear regression was employed to analyze the association between the controlled attenuation parameter (CAP) and liver stiffness measurement (LSM) with ALS. Additionally, multinomial logistic regression was used to investigate the association between ALS and the degree of hepatic steatosis and fibrosis.

RESULTS: Participants had a weighted mean age of 52.69 years and 56.14% were female. In the multivariate linear regression analysis, ALS showed a significant positive correlation with CAP (β = 15.56, 95% CI: 14.50-16.62) and LSM (β = 0.58, 95% CI: 0.48-0.67). Age, healthy dietary level, and PIR had significant interactions with this positive correlation. In the multinomial logistic regression analysis, ALS exhibited a significant positive correlation with different degrees of hepatic steatosis and fibrosis. Consistency of the results was observed in sensitivity analyses using clinical thresholds of ALS.

CONCLUSIONS: Comprehensive clinical assessment targeting load adaptation may enhance the effectiveness of risk assessment in patients with hepatic steatosis and fibrosis.}, } @article {pmid38879333, year = {2024}, author = {Han, Y and Gao, H and Sun, Y and Wang, Y and Yan, C and Ma, H and Liu, X and Huang, Z}, title = {Target gene overexpression and enhanced metabolism confer resistance to nicosulfuron in Eriochloa villosa (Thunb.).}, journal = {Pesticide biochemistry and physiology}, volume = {202}, number = {}, pages = {105946}, doi = {10.1016/j.pestbp.2024.105946}, pmid = {38879333}, issn = {1095-9939}, mesh = {*Sulfonylurea Compounds/pharmacology ; *Acetolactate Synthase/genetics/metabolism/antagonists & inhibitors ; *Herbicide Resistance/genetics ; *Herbicides/pharmacology ; *Pyridines/pharmacology ; Plant Proteins/genetics/metabolism ; Gene Expression Regulation, Plant/drug effects ; Poaceae/genetics/drug effects ; }, abstract = {Eriochloa villosa (Thunb.) Kunth is a troublesome weed widely distributed in maize (Zea mays L.) fields in Northeast China. Many populations of E. villosa have evolved resistance to nicosulfuron herbicides, which inhibit acetolactate synthase (ALS). The objectives of this research were to confirm that E. villosa is resistant to nicosulfuron and to investigate the basis of nicosulfuron resistance. Whole-plant dose-response studies revealed that the R population had not developed a high level of cross-resistance and exhibited greater resistant (25.62-fold) to nicosulfuron than that of the S population and had not yet developed a high level of cross-resistance. An in vitro ALS activity assay demonstrated that the I50 of nicosulfuron was 6.87-fold greater in the R population than the S population. However, based on ALS gene sequencing, the target ALS gene in the R population did not contain mutations. Quantitative real-time polymerase chain reaction (qRT-PCR) revealed that ALS gene expression between the R and S populations was significantly different after nicosulfuron application, but no differences were observed in the gene copy number. After the cytochrome P450 inhibitor malathion or the GST inhibitor NBD-Cl was applied, the resistant E. villosa population exhibited increased sensitivity to nicosulfuron. Based on the activities of GSTs and P450s, the activities of the R population were greater than those of the S population after nicosulfuron application. This is the first report that the resistance of E. villosa to ALS inhibitors results from increased target gene expression and increased metabolism. These findings provide a theoretical foundation for the effective control of herbicide-resistant E. villosa.}, } @article {pmid38879294, year = {2024}, author = {Xu, H and Cheng, J and Leng, Q and Liang, S and Sun, L and Su, W and Xue, F and Wu, R}, title = {Nontarget site-based resistance to nicosulfuron and identification of candidate genes in Cucumis melo L. var. agrestis Naud. via RNA-Seq transcriptome analysis.}, journal = {Pesticide biochemistry and physiology}, volume = {202}, number = {}, pages = {105912}, doi = {10.1016/j.pestbp.2024.105912}, pmid = {38879294}, issn = {1095-9939}, mesh = {*Herbicide Resistance/genetics ; *Sulfonylurea Compounds/pharmacology ; *Herbicides/pharmacology/toxicity ; *Acetolactate Synthase/genetics/metabolism ; *Cucumis melo/genetics/drug effects ; *Pyridines/pharmacology ; RNA-Seq ; Gene Expression Profiling ; Malathion/pharmacology ; Gene Expression Regulation, Plant/drug effects ; Plant Proteins/genetics/metabolism ; }, abstract = {Herbicide resistance is a worldwide concern for weed control. Cucumis melo L. var. agrestis Naud. (C. melo) is an annual trailing vine weed that is commonly controlled by nicosulfuron, acetolactate synthase (ALS)-inhibiting herbicides. However, long-term use of this herbicide has led to the emergence of resistance and several nicosulfuron resistant populations of C. melo have been found. Here we identified a resistant (R) C. melo population exhibiting 7.31-fold resistance to nicosulfuron compared with a reference sensitive (S) population. ALS gene sequencing of the target site revealed no amino acid substitution in R plants, and no difference in enzyme activity, as shown by ALS activity assays in vitro. ALS gene expression was not significantly different before and after the application of nicosulfuron. Pretreatment with the cytochrome P450 monooxygenase (P450) inhibitor malathion reduced nicosulfuron resistance in the R population. RNA-Seq transcriptome analysis was used to identify candidate genes that may confer metabolic resistance to nicosulfuron. We selected genes with annotations related to detoxification functions. A total of 20 candidate genes (7 P450 genes, 1 glutathione S-transferase (GST) gene, 2 ATP-binding cassette (ABC) transporters, and 10 glycosyltransferase (GT)) were identified; 12 of them (7 P450s, 1 GST, 2 ABC transporters, and 2 GTs) were demonstrated significantly differential expression between R and S by quantitative real-time RT-PCR (qRT-PCR). Our findings revealed that the resistance mechanism in C. melo was nontarget-site based. Our results also provide a valuable resource for studying the molecular mechanisms of weed resistance.}, } @article {pmid38879100, year = {2024}, author = {Viccaro, F and Lecci, A and Baccolini, V and Sciurti, A and Piamonti, D and Inghilleri, M and D'Antoni, L and Palange, P}, title = {Prediction of cough effectiveness in amyotrophic lateral sclerosis patients assessed by ultrasuond of the diaphragm during the cough expiration phase.}, journal = {Respiratory physiology & neurobiology}, volume = {327}, number = {}, pages = {104299}, doi = {10.1016/j.resp.2024.104299}, pmid = {38879100}, issn = {1878-1519}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology/complications/diagnostic imaging ; *Cough/physiopathology ; Male ; *Diaphragm/physiopathology/diagnostic imaging ; Female ; Middle Aged ; Aged ; *Ultrasonography ; Exhalation/physiology ; Peak Expiratory Flow Rate/physiology ; Adult ; }, abstract = {Assessing cough effectiveness, using Cough Peak Flow, is crucial for patients with Neuromuscular Diseases, such as Amyotrophic Lateral Sclerosis. Impaired cough function can contribute to respiratory decline and failure. The goal of the study is to determine the correlation between diaphragmatic excursion and cough expiratory phase, potentially utilizing ultrasonographic indices to estimate Cough Peak Flow in these patients. Twenty-two patients were enrolled in this study. The upward displacement of the diaphragm was measured with ultrasonography during voluntary cough expiration and Cough Peak Flow was simultaneously measured. A multivariable linear regression model was built to quantify the association between Cough Peak Flow and diaphragm expiratory excursion. There is significative relationship between Cough Peak Flow and diaphragm excursion with a Pearson's r coefficient of 0.86 observed in the patients group. Multiple linear regression analysis for Cough Peak Flow (Adjusted R[2] = 0.86) revealed significant associations between Cough Peak Flow and expiratory excursion (adjusted β-coefficient: 64.78, 95 %, CI: 51.50-78.07, p<0.001) and sex (adjusted β-coefficient: -69.06; 95 % CI: -109.98 to -28.15, p=0.001). Our results predict the cough effectiveness by using M-mode diaphragmatic sonography with a potentially significant impact on therapeutic choices.}, } @article {pmid38879065, year = {2024}, author = {Ashrafzadeh-Kian, S and Figdore, D and Larson, B and Deters, R and Abou-Diwan, C and Bornhorst, J and Algeciras-Schimnich, A}, title = {Head-to-head comparison of four plasma neurofilament light chain (NfL) immunoassays.}, journal = {Clinica chimica acta; international journal of clinical chemistry}, volume = {561}, number = {}, pages = {119817}, doi = {10.1016/j.cca.2024.119817}, pmid = {38879065}, issn = {1873-3492}, mesh = {Humans ; Immunoassay/methods ; *Neurofilament Proteins/blood ; Multiple Sclerosis/blood/diagnosis ; Biomarkers/blood ; Amyotrophic Lateral Sclerosis/blood/diagnosis ; Female ; Male ; Middle Aged ; }, abstract = {BACKGROUND: Neurofilament Light Chain (NfL) is an emerging blood biomarker of neuro-axonal injury and neurodegeneration with the potential to be used in the clinical management of various neurological conditions. Various NfL immunoassays are in development on high-throughput automated systems, but little information is available related to the comparability between assays. In this study, we performed a head-to-head comparison of four NfL immunoassays using plasma samples from individuals with various neurological conditions.

METHODS: EDTA plasma samples in which NfL was ordered clinically were stratified according to diagnosis. NfL concentrations (pg/mL) in plasma were obtained using the Quanterix Simoa®, the Roche Elecsys, the Siemens Healthineers Atellica®IM, and the Fujirebio Lumipulse® NfL assays. Passing-Bablok regression analyses were performed to assess the correlation and bias between methods. Additionally, the distribution of NfL concentrations for each assay was assessed in three disease groups: amyotrophic lateral sclerosis (ALS) upon initial diagnosis, ALS treated, and multiple sclerosis (MS).

RESULTS: The R[2] between assays were all ≥ 0.95, however, significant proportional bias was observed between some assays. In particular, the Roche Elecsys assay NfL concentrations were significantly lower (∼85 %) when compared against the other three assays. The four assays were comparable with regards to the percentage of patients that were identified as having an elevated NfL result in the various clinical groups: ALS initial diagnoses (83-94 %), ALS untreated (93-100 %), and MS (8-18 %).

CONCLUSIONS: This is the first study describing a head-to-head comparison of four automated NfL immunoassays. We demonstrate that there is a strong correlation between assays but a lack of standardization which is evident by the bias observed between some of the evaluated methods. These analytical differences will be important to consider when using NfL as a biomarker of neurodegeneration.}, } @article {pmid38878774, year = {2024}, author = {Kumbier, K and Roth, M and Li, Z and Lazzari-Dean, J and Waters, C and Hammerlindl, S and Rinaldi, C and Huang, P and Korobeynikov, VA and , and Phatnani, H and Shneider, N and Jacobson, MP and Wu, LF and Altschuler, SJ}, title = {Identifying FUS amyotrophic lateral sclerosis disease signatures in patient dermal fibroblasts.}, journal = {Developmental cell}, volume = {59}, number = {16}, pages = {2134-2142.e6}, doi = {10.1016/j.devcel.2024.05.011}, pmid = {38878774}, issn = {1878-1551}, support = {R01 NS106236/NS/NINDS NIH HHS/United States ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology ; *Fibroblasts/metabolism/pathology ; *RNA-Binding Protein FUS/metabolism/genetics ; Mutation/genetics ; Male ; Female ; Skin/pathology/metabolism ; Machine Learning ; Middle Aged ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a rapidly progressing, highly heterogeneous neurodegenerative disease, underscoring the importance of obtaining information to personalize clinical decisions quickly after diagnosis. Here, we investigated whether ALS-relevant signatures can be detected directly from biopsied patient fibroblasts. We profiled familial ALS (fALS) fibroblasts, representing a range of mutations in the fused in sarcoma (FUS) gene and ages of onset. To differentiate FUS fALS and healthy control fibroblasts, machine-learning classifiers were trained separately on high-content imaging and transcriptional profiles. "Molecular ALS phenotype" scores, derived from these classifiers, captured a spectrum from disease to health. Interestingly, these scores negatively correlated with age of onset, identified several pre-symptomatic individuals and sporadic ALS (sALS) patients with FUS-like fibroblasts, and quantified "movement" of FUS fALS and "FUS-like" sALS toward health upon FUS ASO treatment. Taken together, these findings provide evidence that non-neuronal patient fibroblasts can be used for rapid, personalized assessment in ALS.}, } @article {pmid38878554, year = {2024}, author = {Mincic, AM and Antal, M and Filip, L and Miere, D}, title = {Modulation of gut microbiome in the treatment of neurodegenerative diseases: A systematic review.}, journal = {Clinical nutrition (Edinburgh, Scotland)}, volume = {43}, number = {7}, pages = {1832-1849}, doi = {10.1016/j.clnu.2024.05.036}, pmid = {38878554}, issn = {1532-1983}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Neurodegenerative Diseases/microbiology/therapy ; *Probiotics/administration & dosage/therapeutic use ; *Prebiotics/administration & dosage ; *Dysbiosis/therapy/microbiology ; Animals ; Fecal Microbiota Transplantation ; }, abstract = {BACKGROUND AND AIMS: Microbiota plays an essential role in maintaining body health, through positive influences on metabolic, defensive, and trophic processes and on intercellular communication. Imbalance in intestinal flora, with the proliferation of harmful bacterial species (dysbiosis) is consistently reported in chronic illnesses, including neurodegenerative diseases (ND). Correcting dysbiosis can have a beneficial impact on the symptoms and evolution of ND. This review examines the effects of microbiota modulation through administration of probiotics, prebiotics, symbiotics, or prebiotics' metabolites (postbiotics) in patients with ND like multiple sclerosis (MS), Alzheimer's disease (AD), Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS).

METHODS: PubMed, Web of Science, Medline databases and ClinicalTrials.gov registry searches were performed using pre-/pro-/postbiotics and ND-related terms. Further references were obtained by checking relevant articles.

RESULTS: Although few compared to animal studies, the human studies generally show positive effects on disease-specific symptoms, overall health, metabolic parameters, on oxidative stress and immunological markers. Therapy with probiotics in various forms (mixtures of bacterial strains, fecal microbiota transplant, diets rich in fermented foods) exert favorable effects on patients' mental health, cognition, and quality of life, targeting pathogenetic ND mechanisms and inducing reparatory mechanisms at the cellular level. More encouraging results have been observed in prebiotic/postbiotic therapy in some ND.

CONCLUSIONS: The effects of probiotic-related interventions depend on the patients' ND stage and pre-existing allopathic medication. Further studies on larger cohorts and long term comprehensive neuropsychiatric, metabolic, biochemical testing, and neuroimaging monitoring are necessary to optimize therapeutic protocols in ND.}, } @article {pmid38878150, year = {2025}, author = {Wang, F and Wen, H and Liu, L and Aisa, HA and Xin, X}, title = {A Pair of Epimers of Lignan Alleviate Neuroinflammatory Effects by Modulating iNOS/COX-2 and MAPK/NF-κB Signaling Pathways.}, journal = {Inflammation}, volume = {48}, number = {1}, pages = {361-371}, pmid = {38878150}, issn = {1573-2576}, support = {2020YFE0205600//the National Key Research and Development Program of China/ ; U1703235//the National Natural Science Foundation of China/ ; }, mesh = {*Lignans/pharmacology/chemistry ; *Cyclooxygenase 2/metabolism ; Animals ; *Nitric Oxide Synthase Type II/metabolism/antagonists & inhibitors ; Mice ; *NF-kappa B/metabolism ; *MAP Kinase Signaling System/drug effects ; *Neuroinflammatory Diseases/drug therapy/metabolism ; Signal Transduction/drug effects ; *Anti-Inflammatory Agents/pharmacology ; Cell Line ; Lipopolysaccharides ; Microglia/drug effects ; }, abstract = {Neuroinflammation is a causative factor in neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease and amyotrophic lateral sclerosis. Previous studies have shown that Artemisia mongolica has anti-inflammatory properties. Aschantin (AM3) has been shown to have anti-inflammatory effects. However, the mechanism of AM3 and its epimer epi-aschantin (AM2) remains controversial. Therefore, the present study explored the mechanism of neuroinflammation by AM2 and AM3 and attempted to reveal the relationship between the structure of AM2 and AM3 and anti-neuroinflammatory activity. We isolated for the first time 12 lignans from A. mongolica that inhibited NO content at 10 μM in LPS-stimulated BV2 cells. Among them, epi-aschantin (AM2) and Aschantin (AM3) showed significant inhibition in NO screening. With further studies, we found that both AM2 and AM3 effectively inhibited the overproduction of NO, PGE2, IL-6, TNF-α and MCP-1, as well as the overexpression of COX-2 and iNOS. Mechanistic studies have shown AM2 and AM3 significantly inhibited the phosphorylation of ERK, JNK and P-38 in the MAPK signaling pathway and p-IκBα,p-p65 and blocked p65 entry into the nucleus. The results suggested that the pair of epimers (AM2 and AM3) can be used as potential therapeutic agents in the treatment of various brain disorders and that structural differences do not differ in anti-neuroinflammatory effects.}, } @article {pmid38878106, year = {2024}, author = {Chourpiliadis, C and Seitz, C and Lovik, A and Joyce, EE and Pan, L and Hu, Y and Kläppe, U and Samuelsson, K and Press, R and Ingre, C and Fang, F}, title = {Lifestyle and medical conditions in relation to ALS risk and progression-an introduction to the Swedish ALSrisc Study.}, journal = {Journal of neurology}, volume = {271}, number = {8}, pages = {5447-5459}, pmid = {38878106}, issn = {1432-1459}, support = {R01TS000324-01-00//US Center for Disease Control and Prevention/ ; 2019-01088//Swedish Research Council/ ; 2023-02428//Swedish Research Council/ ; MegaALS 802091//European Research Council Starting Grant/ ; R01 TS000324/TS/ATSDR CDC HHS/United States ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/epidemiology/diagnosis ; Male ; Sweden/epidemiology ; Female ; Middle Aged ; Aged ; *Life Style ; *Disease Progression ; *Body Mass Index ; Adult ; Risk Factors ; Smoking/epidemiology ; Diabetes Mellitus/epidemiology ; Hypertension/epidemiology ; Hypercholesterolemia/epidemiology ; }, abstract = {BACKGROUND: This study was an introduction to the Swedish ALSrisc Study and explored the association of lifestyle and medical conditions, with risk and progression of amyotrophic lateral sclerosis (ALS).

METHODS: We included 265 newly diagnosed ALS patients during 2016-2022 in Stockholm and 207 ALS-free siblings and partners of the patients as controls. Information on body mass index (BMI), smoking, and history of head injuries, diabetes mellitus, hypercholesterolemia, and hypertension was obtained through the Euro-MOTOR questionnaire at recruitment. Patients were followed from diagnosis until death, invasive ventilation, or November 30, 2022.

RESULTS: Higher BMI at recruitment was associated with lower risk for ALS (OR 0.89, 95%CI 0.83-0.95), especially among those diagnosed after 65 years. One unit increase in the average BMI during the 3 decades before diagnosis was associated with a lower risk for ALS (OR 0.94, 95%CI 0.89-0.99). Diabetes was associated with lower risk of ALS (OR 0.38, 95%CI 0.16-0.90), while hypercholesterolemia was associated with higher risk of ALS (OR 2.10, 95%CI 1.13-3.90). Higher BMI at diagnosis was associated with lower risk of death (HR 0.91, 95%CI 0.84-0.98), while the highest level of smoking exposure (in pack-years) (HR 1.90, 95%CI 1.20-3.00), hypercholesterolemia (HR 1.84, 95%CI 1.06-3.19), and hypertension (HR 1.76, 95%CI 1.03-3.01) were associated with higher risk of death, following ALS diagnosis.

CONCLUSIONS: Higher BMI and diabetes were associated with lower risk of ALS. Higher BMI was associated with lower risk of death, whereas smoking (especially in high pack-years), hypercholesterolemia, and hypertension were associated with higher risk of death after ALS diagnosis.}, } @article {pmid38877004, year = {2024}, author = {Costa, RG and Conceição, A and Matos, CA and Nóbrega, C}, title = {The polyglutamine protein ATXN2: from its molecular functions to its involvement in disease.}, journal = {Cell death & disease}, volume = {15}, number = {6}, pages = {415}, pmid = {38877004}, issn = {2041-4889}, mesh = {Humans ; *Ataxin-2/metabolism/genetics ; *Peptides/metabolism/genetics ; Animals ; Amyotrophic Lateral Sclerosis/metabolism/genetics/pathology ; Spinocerebellar Ataxias/metabolism/genetics/pathology ; }, abstract = {A CAG repeat sequence in the ATXN2 gene encodes a polyglutamine (polyQ) tract within the ataxin-2 (ATXN2) protein, showcasing a complex landscape of functions that have been progressively unveiled over recent decades. Despite significant progresses in the field, a comprehensive overview of the mechanisms governed by ATXN2 remains elusive. This multifaceted protein emerges as a key player in RNA metabolism, stress granules dynamics, endocytosis, calcium signaling, and the regulation of the circadian rhythm. The CAG overexpansion within the ATXN2 gene produces a protein with an extended poly(Q) tract, inducing consequential alterations in conformational dynamics which confer a toxic gain and/or partial loss of function. Although overexpanded ATXN2 is predominantly linked to spinocerebellar ataxia type 2 (SCA2), intermediate expansions are also implicated in amyotrophic lateral sclerosis (ALS) and parkinsonism. While the molecular intricacies await full elucidation, SCA2 presents ATXN2-associated pathological features, encompassing autophagy impairment, RNA-mediated toxicity, heightened oxidative stress, and disruption of calcium homeostasis. Presently, SCA2 remains incurable, with patients reliant on symptomatic and supportive treatments. In the pursuit of therapeutic solutions, various studies have explored avenues ranging from pharmacological drugs to advanced therapies, including cell or gene-based approaches. These endeavours aim to address the root causes or counteract distinct pathological features of SCA2. This review is intended to provide an updated compendium of ATXN2 functions, delineate the associated pathological mechanisms, and present current perspectives on the development of innovative therapeutic strategies.}, } @article {pmid38876745, year = {2024}, author = {van Selms, MKA and van der Linden, MW and van der Meijden, C and Lobbezoo, F}, title = {A call for optimal oral care in patients with ALS.}, journal = {The Lancet. Neurology}, volume = {23}, number = {7}, pages = {670}, doi = {10.1016/S1474-4422(24)00226-6}, pmid = {38876745}, issn = {1474-4465}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy ; Oral Hygiene ; }, } @article {pmid38876730, year = {2024}, author = {The Lancet Neurology, }, title = {Multidisciplinary care for amyotrophic lateral sclerosis.}, journal = {The Lancet. Neurology}, volume = {23}, number = {7}, pages = {649}, doi = {10.1016/S1474-4422(24)00227-8}, pmid = {38876730}, issn = {1474-4465}, mesh = {*Amyotrophic Lateral Sclerosis/therapy ; Humans ; *Patient Care Team ; }, } @article {pmid38876108, year = {2024}, author = {Scaber, J and Thomas-Wright, I and Clark, AJ and Xu, Y and Vahsen, BF and Carcolé, M and Dafinca, R and Farrimond, L and Isaacs, AM and Bennett, DL and Talbot, K}, title = {Cellular and axonal transport phenotypes due to the C9ORF72 HRE in iPSC motor and sensory neurons.}, journal = {Stem cell reports}, volume = {19}, number = {7}, pages = {957-972}, pmid = {38876108}, issn = {2213-6711}, support = {MR/T020113/1/MRC_/Medical Research Council/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; }, mesh = {*Induced Pluripotent Stem Cells/metabolism/cytology ; *C9orf72 Protein/genetics/metabolism ; Humans ; *Motor Neurons/metabolism ; *Sensory Receptor Cells/metabolism ; *Axonal Transport ; *Amyotrophic Lateral Sclerosis/genetics/metabolism ; *Phenotype ; *DNA Repeat Expansion/genetics ; }, abstract = {Induced pluripotent stem cell (iPSC)-derived motor neurons (MNs) from patients with amyotrophic lateral sclerosis (ALS) and the C9ORF72 hexanucleotide repeat expansion (HRE) have multiple cellular phenotypes, but which of these accurately reflect the biology underlying the cell-specific vulnerability of ALS is uncertain. We therefore compared phenotypes due to the C9ORF72 HRE in MNs with sensory neurons (SNs), which are relatively spared in ALS. The iPSC models were able to partially reproduce the differential gene expression seen between adult SNs and MNs. We demonstrated that the typical hallmarks of C9ORF72-ALS, including RNA foci and dipeptide formation, as well as specific axonal transport defects, occurred equally in MNs and SNs, suggesting that these in vitro phenotypes are not sufficient to explain the cell-type selectivity of ALS in isolation.}, } @article {pmid38875517, year = {2024}, author = {Michielsen, A and van Veenhuijzen, K and Janse van Mantgem, MR and van Es, MA and Veldink, JH and van Eijk, RPA and van den Berg, LH and Westeneng, HJ}, title = {Association Between Hypothalamic Volume and Metabolism, Cognition, and Behavior in Patients With Amyotrophic Lateral Sclerosis.}, journal = {Neurology}, volume = {103}, number = {2}, pages = {e209603}, pmid = {38875517}, issn = {1526-632X}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism/diagnostic imaging/pathology ; Male ; Female ; Middle Aged ; *Hypothalamus/diagnostic imaging/metabolism/pathology ; *Magnetic Resonance Imaging ; Aged ; Cross-Sectional Studies ; Longitudinal Studies ; Disease Progression ; Cognition/physiology ; Adult ; Energy Metabolism/physiology ; }, abstract = {BACKGROUND AND OBJECTIVES: Dysfunction of energy metabolism, cognition, and behavior are important nonmotor symptoms of amyotrophic lateral sclerosis (ALS), negatively affecting survival and quality of life, but poorly understood. Neuroimaging is ideally suited to studying nonmotor neurodegeneration in ALS, but few studies have focused on the hypothalamus, a key region for regulating energy homeostasis, cognition, and behavior. We evaluated, therefore, hypothalamic neurodegeneration in ALS and explored the relationship between hypothalamic volumes and dysregulation of energy metabolism, cognitive and behavioral changes, disease progression, and survival.

METHODS: Patients with ALS and population-based controls were included for this cross-sectional and longitudinal MRI study. The hypothalamus was segmented into 5 subregions and their volumes were calculated. Linear (mixed) models, adjusted for age, sex, and total intracranial volume, were used to compare hypothalamic volumes between groups and to analyze associations with metabolism, cognition, behavior, and disease progression. Cox proportional hazard models were used to investigate the relationship of hypothalamic volumes with survival. Permutation-based corrections for multiple hypothesis testing were applied to all analyses to control the family-wise error rate.

RESULTS: Data were available for 564 patients with ALS and 356 controls. The volume of the anterior superior subregion of the hypothalamus was smaller in patients with ALS than in controls (β = -0.70 [-1.15 to -0.25], p = 0.013). Weight loss, memory impairments, and behavioral disinhibition were associated with a smaller posterior hypothalamus (β = -4.79 [-8.39 to -2.49], p = 0.001, β = -10.14 [-15.88 to -4.39], p = 0.004, and β = -12.09 [-18.83 to -5.35], p = 0.003, respectively). Furthermore, the volume of this subregion decreased faster over time in patients than in controls (β = -0.25 [0.42 to -0.09], p = 0.013), and a smaller volume of this structure was correlated with shorter survival (hazard ratio = 0.36 [0.21-0.61], p = 0.029).

DISCUSSION: We obtained evidence for hypothalamic involvement in ALS, specifically marked by atrophy of the anterior superior subregion. Moreover, we found that atrophy of the posterior hypothalamus was associated with weight loss, memory dysfunction, behavioral disinhibition, and survival, and that this subregion deteriorated faster in patients with ALS than in controls. These findings improve our understanding of nonmotor involvement in ALS and could contribute to the identification of new treatment targets for this devastating disease.}, } @article {pmid38875513, year = {2024}, author = {van Eijk, RPA and van den Berg, LH and Lu, Y}, title = {Cultivating Patient Preferences in ALS Clinical Trials: Reliability and Prognostic Value of the Patient-Ranked Order of Function.}, journal = {Neurology}, volume = {103}, number = {2}, pages = {e209502}, pmid = {38875513}, issn = {1526-632X}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy/diagnosis/physiopathology ; Male ; Female ; Middle Aged ; *Patient Preference ; Reproducibility of Results ; Prognosis ; Aged ; Netherlands ; Clinical Trials as Topic ; Surveys and Questionnaires ; Registries ; }, abstract = {BACKGROUND AND OBJECTIVES: The Patient-Ranked Order of Function (PROOF) is a novel approach to account for patient-reported preferences in the evaluation of treatments of amyotrophic lateral sclerosis (ALS). In this study, we assess the reliability and prognostic value of different sets of patient-reported preferences that can be used for the PROOF end point.

METHODS: Data were obtained through online surveys over the course of 12 months using the population-based registry of the Netherlands. Patients were asked to score functional domains of the ALS Functional Rating Scale (ALSFRS-R) and rank the order of importance of each domain. Two weeks after the initial invite, the questionnaire was repeated to evaluate test-retest reliability. Vital status was extracted from the municipal population register.

RESULTS: In total, 611 patients with ALS were followed up for survival and 382 patients were included in the test-retest reliability study. All versions of PROOF, using different sets of preferences, resulted in excellent reliability (intraclass correlation coefficients ranged from 0.89 [95% CI 0.87-0.91] to 0.97 [95% CI 0.97-0.98], all p < 0.001), without systematic differences between baseline and week 2 (mean rank difference range -1 to -3 [95% CI range -8 to 2], all p > 0.20). Preferences about future events were more variable than preferences about current symptoms. All versions of PROOF strongly predicted overall survival (hazard ratios per 10th rank percentile ranged from 0.80 to 0.83 [95% CI range 0.76-0.87], all p < 0.001) and had a more even separation of survival curves between rank-stratified subgroups compared with the ALSFRS-R total score.

DISCUSSION: In a large cohort of patients, we show how patient-reported preferences can be measured and integrated reliably with the ALSFRS-R without leading to systematic bias. Patient preferences may provide unique prognostic information in addition to what is already measured conventionally. This could provide a more comprehensive understanding of how medical interventions effectively address the patient's concerns and improve what matters most to them.}, } @article {pmid38875346, year = {2024}, author = {}, title = {Erratum for the Research Article: "Sulfated disaccharide protects membrane and DNA damages from arginine-rich dipeptide repeats in ALS" by Chang et al.}, journal = {Science advances}, volume = {10}, number = {24}, pages = {eadq7259}, doi = {10.1126/sciadv.adq7259}, pmid = {38875346}, issn = {2375-2548}, } @article {pmid38874845, year = {2024}, author = {Birbaumer, N}, title = {"Your Thoughts are (were) Free!": Brain-Computer-Interfaces, Neurofeedback, Detection of Deception, and the Future of Mind-Reading.}, journal = {Applied psychophysiology and biofeedback}, volume = {}, number = {}, pages = {}, pmid = {38874845}, issn = {1573-3270}, abstract = {This review describes the historical developement and rationale of clinically relevant research on neurophysiological "mind reading" paradims: Brain- Computer-Interfaces, detection of deception, brain stimulation and neurofeedback and the clinical applications in drug resistant epilepsy, chronic stroke, and communication with paralyzed locked-in persons. The emphasis lies on completely locked-in patients with amyotrophic lateral sclerosis using non-invasive and invasive brain computer interfaces and neurofeedback to restore verbal communication with the social environment. In the second part of the article we argue that success and failure of neurophysiological "mind reading" paradigms may be explained with a motor theory of thinking and emotion in combination with learning theory. The ethical implications of brain computer interface and neurofeedback approaches, particularly for severe chronic paralysis and loss of communication diseases and decisions on hastened death and euthanasia are discussed.}, } @article {pmid38873369, year = {2024}, author = {Hong, J and Kim, GC and Cha, JG and Park, J and Park, B and Park, SY and Kim, SU}, title = {Transcholecystic Duodenal Drainage as an Alternative Decompression Method for Afferent Loop Syndrome: Two Case Reports.}, journal = {Journal of the Korean Society of Radiology}, volume = {85}, number = {3}, pages = {661-667}, pmid = {38873369}, issn = {2951-0805}, abstract = {Afferent loop syndrome (ALS) is a rare complication of gastrectomies and gastrointestinal reconstruction. This can predispose patients to fatal conditions, such as cholangitis, pancreatitis, and duodenal perforation with peritonitis. Therefore, emergency decompression is necessary to prevent these complications. Herein, we report two cases in which transcholecystic duodenal drainage, an alternative decompression treatment, was performed in ALS patients without bile duct dilatation. Two patients who underwent distal gastrectomy with Billroth II anastomosis sought consultation in an emergency department for epigastric pain and vomiting. On CT, ALS with acute pancreatitis was diagnosed. However, biliary access could not be achieved because of the absence of bile duct dilatation. To overcome this problem, a duodenal drainage catheter was placed to decompress the afferent loop after traversing the cystic duct via a transcholecystic approach. The patients were discharged without additional surgical treatment 2 weeks and 1 month after drainage.}, } @article {pmid38872308, year = {2024}, author = {Çelik, MH and Gagneur, J and Lim, RG and Wu, J and Thompson, LM and Xie, X}, title = {Identifying dysregulated regions in amyotrophic lateral sclerosis through chromatin accessibility outliers.}, journal = {HGG advances}, volume = {5}, number = {3}, pages = {100318}, pmid = {38872308}, issn = {2666-2477}, mesh = {*Amyotrophic Lateral Sclerosis/genetics/metabolism ; Humans ; *Chromatin/metabolism/genetics ; Promoter Regions, Genetic/genetics ; Algorithms ; Gene Expression Regulation ; Chromatin Immunoprecipitation Sequencing ; Histones/metabolism/genetics ; }, abstract = {The high heritability of amyotrophic lateral sclerosis (ALS) contrasts with its low molecular diagnosis rate post-genetic testing, pointing to potential undiscovered genetic factors. To aid the exploration of these factors, we introduced EpiOut, an algorithm to identify chromatin accessibility outliers that are regions exhibiting divergent accessibility from the population baseline in a single or few samples. Annotation of accessible regions with histone chromatin immunoprecipitation sequencing and Hi-C indicates that outliers are concentrated in functional loci, especially among promoters interacting with active enhancers. Across different omics levels, outliers are robustly replicated, and chromatin accessibility outliers are reliable predictors of gene expression outliers and aberrant protein levels. When promoter accessibility does not align with gene expression, our results indicate that molecular aberrations are more likely to be linked to post-transcriptional regulation rather than transcriptional regulation. Our findings demonstrate that the outlier detection paradigm can uncover dysregulated regions in rare diseases. EpiOut is available at github.com/uci-cbcl/EpiOut.}, } @article {pmid38872258, year = {2024}, author = {Xiong, B and Yang, C and Yang, X and Luo, S and Li, S and Chen, C and He, K and Nie, L and Li, P and Li, S and Huang, H and Liu, J and Zhang, Z and Xie, Y and Zou, L and Yang, X}, title = {Arctigenin derivative A-1 ameliorates motor dysfunction and pathological manifestations in SOD1[G93A] transgenic mice via the AMPK/SIRT1/PGC-1α and AMPK/SIRT1/IL-1β/NF-κB pathways.}, journal = {CNS neuroscience & therapeutics}, volume = {30}, number = {6}, pages = {e14692}, pmid = {38872258}, issn = {1755-5949}, support = {SZSM201611090//Sanming Project of Medicine in Shenzhen/ ; 82171583//National Natural Science Foundation of China/ ; JCYJ20200109144418639//The Key Basic Research Program of Shenzhen Science and Technology Innovation Commission/ ; JCYJ20200109150717745//The Key Basic Research Program of Shenzhen Science and Technology Innovation Commission/ ; SZXK069//Shenzhen Key Medical Discipline Construction Fund/ ; }, mesh = {Animals ; *Mice, Transgenic ; *Sirtuin 1/metabolism ; Mice ; *NF-kappa B/metabolism ; *AMP-Activated Protein Kinases/metabolism ; *Furans/pharmacology ; *Amyotrophic Lateral Sclerosis/drug therapy/pathology/metabolism ; *Interleukin-1beta/metabolism ; *Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism ; Lignans/pharmacology/therapeutic use ; Signal Transduction/drug effects ; Superoxide Dismutase-1/genetics/metabolism ; Male ; Motor Neurons/drug effects/pathology/metabolism ; Spinal Cord/drug effects/pathology/metabolism ; }, abstract = {AIM: Amyotrophic lateral sclerosis (ALS) is a severe neurodegenerative disease characterized by progressive death of upper and lower motor neurons, leading to generalized muscle atrophy, paralysis, and even death. Mitochondrial damage and neuroinflammation play key roles in the pathogenesis of ALS. In the present study, the efficacy of A-1, a derivative of arctigenin with AMP-activated protein kinase (AMPK) and silent information regulator 1 (SIRT1) activation for ALS, was investigated.

METHODS: A-1 at 33.3 mg/kg was administrated in SOD1[G93A] transgenic mice orally from the 13th week for a 6-week treatment period. Motor ability was assessed before terminal anesthesia. Muscle atrophy and fibrosis, motor neurons, astrocytes, and microglia in the spinal cord were evaluated by H&E, Masson, Sirius Red, Nissl, and immunohistochemistry staining. Protein expression was detected with proteomics analysis, Western blotting, and ELISA. Mitochondrial adenosine triphosphate (ATP) and malondialdehyde (MDA) levels were measured using an assay kit.

RESULTS: A-1 administration in SOD1[G93A] mice enhanced mobility, decreased skeletal muscle atrophy and fibrosis, mitigated loss of spinal motor neurons, and reduced glial activation. Additionally, A-1 treatment improved mitochondrial function, evidenced by elevated ATP levels and increased expression of key mitochondrial-related proteins. The A-1 treatment group showed decreased levels of IL-1β, pIκBα/IκBα, and pNF-κB/NF-κB.

CONCLUSIONS: A-1 treatment reduced motor neuron loss, improved gastrocnemius atrophy, and delayed ALS progression through the AMPK/SIRT1/PGC-1α pathway, which promotes mitochondrial biogenesis. Furthermore, the AMPK/SIRT1/IL-1β/NF-κB pathway exerted neuroprotective effects by reducing neuroinflammation. These findings suggest A-1 as a promising therapeutic approach for ALS.}, } @article {pmid38871941, year = {2025}, author = {Naik, B and Sasikumar, J and Das, SP}, title = {From Skin and Gut to the Brain: The Infectious Journey of the Human Commensal Fungus Malassezia and Its Neurological Consequences.}, journal = {Molecular neurobiology}, volume = {62}, number = {1}, pages = {533-556}, pmid = {38871941}, issn = {1559-1182}, support = {GIA/2019/000620/PRCGIA//Indian Council of Medical Research/ ; }, mesh = {Animals ; Humans ; *Brain/microbiology/pathology ; *Malassezia/genetics/isolation & purification/pathogenicity ; *Nervous System Diseases/diagnosis/microbiology/pathology ; *Skin/microbiology ; }, abstract = {The human mycobiome encompasses diverse communities of fungal organisms residing within the body and has emerged as a critical player in shaping health and disease. While extensive research has focused on the skin and gut mycobiome, recent investigations have pointed toward the potential role of fungal organisms in neurological disorders. Among those fungal organisms, the presence of the commensal fungus Malassezia in the brain has created curiosity because of its commensal nature and primary association with the human skin and gut. This budding yeast is responsible for several diseases, such as Seborrheic dermatitis, Atopic dermatitis, Pityriasis versicolor, Malassezia folliculitis, dandruff, and others. However recent findings surprisingly show the presence of Malassezia DNA in the brain and have been linked to diseases like Alzheimer's disease, Parkinson's disease, Multiple sclerosis, and Amyotrophic lateral sclerosis. The exact role of Malassezia in these disorders is unknown, but its ability to infect human cells, travel through the bloodstream, cross the blood-brain barrier, and reside along with the lipid-rich neuronal cells are potential mechanisms responsible for pathogenesis. This also includes the induction of pro-inflammatory cytokines, disruption of the blood-brain barrier, gut-microbe interaction, and accumulation of metabolic changes in the brain environment. In this review, we discuss these key findings from studies linking Malassezia to neurological disorders, emphasizing the complex and multifaceted nature of these cases. Furthermore, we discuss potential mechanisms through which Malassezia might contribute to the development of neurological conditions. Future investigations will open up new avenues for our understanding of the fungal gut-brain axis and how it influences human behavior. Collaborative research efforts among microbiologists, neuroscientists, immunologists, and clinicians hold promise for unraveling the enigmatic connections between human commensal Malassezia and neurological disorders.}, } @article {pmid38870925, year = {2025}, author = {Hamdi, N and Ocab, O and Soliman, R and Ludolph, A and Anwar, W and Logroscino, G and Fahmy, N}, title = {Motor Neuron Disease Population-Based Registry in Egypt: Where Do We Stand?.}, journal = {Neuroepidemiology}, volume = {59}, number = {3}, pages = {277-289}, doi = {10.1159/000539468}, pmid = {38870925}, issn = {1423-0208}, mesh = {Humans ; Egypt/epidemiology ; *Registries ; *Motor Neuron Disease/epidemiology ; *Amyotrophic Lateral Sclerosis/epidemiology ; Prevalence ; Incidence ; }, abstract = {BACKGROUND: There is a growing body of evidence indicating that the worldwide distribution of amyotrophic lateral sclerosis (ALS) is far from uniform. This is evident through variations in the epidemiology, genetics, and phenotypical characteristics of ALS and other motor neuron diseases (MND) across different regions. However, comprehensive ALS epidemiological studies are still lacking in many parts of the world, especially in Africa. Therefore, we propose the establishment of a population-based register for ALS/MND in Egypt, an important part of Africa with a population of more than 100 millions of people.

SUMMARY: Given Egypt's distinctive social and demographic characteristics, it is highly recommended to employ specific, recently developed epidemiological techniques for assessing the prevalence and incidence of these diseases within the country. By utilizing these methods, we can gather invaluable data that will contribute to a deeper understanding of ALS and enable us to effectively address its impact on the population of Egypt.

KEY MESSAGES: Our goal with this pioneering ALS/MND population-based register in Egypt is to define the burden of ALS in this part of Africa and to increase the chances for this consanguineous population to get access to modern individualized genetic therapies. Additionally, we aspire to uncover potential environmental factors and gene-environment interactions that contribute to the development of ALS. This knowledge of MND individual and group risk in Egypt will not only open doors for interventions but also provide opportunities for future research and discovery.}, } @article {pmid38870470, year = {2024}, author = {McDool, E and Carlton, J and Powell, PA and Coates, E and Knox, L and Mayberry, E and Appleby, N and Griffiths, AW and Hobson, E and McDermott, CJ}, title = {Measuring Health-Related Quality of Life in Amyotrophic Lateral Sclerosis: A Systematic Review and Conceptual Framework.}, journal = {Neurology}, volume = {103}, number = {2}, pages = {e209549}, pmid = {38870470}, issn = {1526-632X}, mesh = {*Amyotrophic Lateral Sclerosis/psychology/physiopathology ; Humans ; *Quality of Life/psychology ; Patient Reported Outcome Measures ; }, abstract = {BACKGROUND AND OBJECTIVES: The assessment of health-related quality of life (HRQoL) in patients with amyotrophic lateral sclerosis (ALS) is heterogeneous and inconsistent. The objectives of this study were (1) to develop a comprehensive conceptual framework of HRQoL in ALS and (2) map the content of existing patient-reported outcome measures (PROMs) used in ALS to this novel framework.

METHODS: Our model of HRQoL in ALS (Health-related Quality of life in Amyotrophic Lateral Sclerosis, QuALS) was developed from a systematic literature review and consultative input from key stakeholders (patients, carers, and health care professionals). Five electronic databases were searched in April 2022. Primary studies of any design that assessed HRQoL in ALS by using a multi-item PROM and/or qualitative methods were identified. Using an a priori framework, HRQoL themes were extracted and iteratively modified from the content of each PROM and qualitative study quotations identified in the literature. The conceptual framework was ratified by stakeholders with lived experience and clinical experts. The QuALS framework was used to map the content of identified PROMs and qualitative studies based on thematic coverage.

RESULTS: QuALS covers 3 high-level domains of HRQoL (physical, psychological, and social functioning) and consists of 7 themes (Activities; Physical Health; Autonomy; Cognition; Feelings and Emotions; Self-identity; Relationships), characterized by 42 subthemes. Of 8,220 studies identified, 274 were included in the review that informed QuALS. In these studies, 111 PROMs were used to assess at least 1 aspect of HRQoL, and 11 studies used qualitative methods. Of the 3 high-level domains, physical functioning was the most commonly assessed, particularly within ALS-specific PROMs where almost one-quarter of PROMs exclusively assessed physical functioning. None of the PROMs or qualitative studies identified assessed all aspects of HRQoL in the QuALS framework.

DISCUSSION: This study presents a new comprehensive conceptual framework of HRQoL in ALS (QuALS), informed by a robust systematic review of existing literature and stakeholder input, incorporating lived experience. QuALS provides a valuable resource for researchers and clinicians interested in taking a holistic approach to assessing and understanding the full impact of ALS on HRQoL and how this may be affected by treatments.}, } @article {pmid38869826, year = {2024}, author = {Wang, H and Zeng, R}, title = {Aberrant protein aggregation in amyotrophic lateral sclerosis.}, journal = {Journal of neurology}, volume = {271}, number = {8}, pages = {4826-4851}, pmid = {38869826}, issn = {1432-1459}, mesh = {*Amyotrophic Lateral Sclerosis/metabolism ; Humans ; *Protein Aggregation, Pathological/metabolism ; Protein Aggregates/physiology ; Animals ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal disease. As its pathological mechanisms are not well understood, there are no efficient therapeutics for it at present. While it is highly heterogenous both etiologically and clinically, it has a common salient hallmark, i.e., aberrant protein aggregation (APA). The upstream pathogenesis and the downstream effects of APA in ALS are sophisticated and the investigation of this pathology would be of consequence for understanding ALS. In this paper, the pathomechanism of APA in ALS and the candidate treatment strategies for it are discussed.}, } @article {pmid38869076, year = {2024}, author = {Ye, Y and Jia, P and Miao, J and Wang, Y and Li, Z and Lin, Y and He, M and Liu, S and Zheng, BR and Wu, J and Pan, J and Li, CM and Hou, P and Guo, D}, title = {CCDC50 mediates the clearance of protein aggregates to prevent cellular proteotoxicity.}, journal = {Autophagy}, volume = {20}, number = {11}, pages = {2529-2539}, pmid = {38869076}, issn = {1554-8635}, mesh = {Animals ; *Autophagy/physiology ; Humans ; Mice ; *Protein Aggregates ; Neurons/metabolism ; Cell Survival ; Brain/metabolism/pathology ; Proteostasis ; Neurodegenerative Diseases/metabolism/genetics ; Ubiquitination ; Protein Aggregation, Pathological/metabolism ; }, abstract = {Protein aggregation caused by the disruption of proteostasis will lead to cellular cytotoxicity and even cell death, which is implicated in multiple neurodegenerative diseases. The elimination of aggregated proteins is mediated by selective macroautophagy receptors, which is termed aggrephagy. However, the identity and redundancy of aggrephagy receptors in recognizing substrates remain largely unexplored. Here, we find that CCDC50, a highly expressed autophagy receptor in brain, is recruited to proteotoxic stresses-induced polyubiquitinated protein aggregates and ectopically expressed aggregation-prone proteins. CCDC50 recognizes and further clears these cytotoxic aggregates through autophagy. The ectopic expression of CCDC50 increases the tolerance to stress-induced proteotoxicity and hence improved cell survival in neuron cells, whereas CCDC50 deficiency caused accumulation of lipid deposits and polyubiquitinated protein conjugates in the brain of one-year-old mice. Our study illustrates how aggrephagy receptor CCDC50 combats proteotoxic stress for the benefit of neuronal cell survival, thus suggesting a protective role in neurotoxic proteinopathy.Abbreviations: AD: Alzheimer disease; ALS: amyotrophic lateral sclerosis; ATG5: autophagy related 5; BODIPY: boron-dipyrromethene; CASP3: caspase 3; CCDC50: coiled-coil domain containing 50; CCT2: chaperonin containing TCP1 subunit 2; CHX: cycloheximide; CQ: chloroquine; CRISPR: clustered regulatory interspaced short palindromic repeat; Cas9: CRISPR-associated system 9; DAPI: 4',6-diamidino-2-phenylindole; FK2: Anti-ubiquitinylated proteins antibody, clone FK2; FUS: FUS RNA binding protein; GFP: green fluorescent protein; HD: Huntington disease; HTT: huntingtin; KEGG: Kyoto Encyclopedia of Genes and Genomes; LDS: LIR-docking site; LIR: LC3-interacting region; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MAPT/tau: microtubule associated protein tau; MIU: motif interacting with ubiquitin; NBR1: NBR1, autophagy cargo receptor; OPTN: optineurin; PD: Parkinson disease; PI: propidium iodide; ROS: reactive oxygen species; SOD1: superoxide dismutase 1; SQSTM1/p62: sequestosome 1; TAX1BP1: Tax1 binding protein 1; Ub: ubiquitin; UDS: UIM-docking site; UIM: ubiquitin interacting motif; UPS: ubiquitin-proteasome system.}, } @article {pmid38868068, year = {2024}, author = {Nuredini, A and Bottignole, D and Stragliati, F and Anceschi, P and Romano, S and Pollara, I and Abramo, A and Rausa, F and Parrino, L and Zinno, L and Mutti, C}, title = {Unraveling sleep respiratory dysfunction in amyotrophic lateral sclerosis: Beyond the apnea-hypopnea index and sleep-related hypoxia.}, journal = {Heliyon}, volume = {10}, number = {11}, pages = {e32250}, pmid = {38868068}, issn = {2405-8440}, abstract = {The timely introduction of non-invasive ventilation (NIV) is extremely relevant in the multidisciplinary management of patients affected by amyotrophic lateral sclerosis (ALS) and is based on the proper identification of red flags for early diaphragmatic exhaustion. Polygraphic sleep recording may provide insightful information on the ongoing respiratory impairment; in particular, atypical breathing patterns need to be recognized, as the application of current guidelines for sleep-related hypoxemia or sleep apnea may be insufficient for detecting early signs of diaphragmatic fatigue. We report the case of a 51-year-old man affected by ALS who was asymptomatic for breathing impairment, but whose nocturnal polysomnographic recording, despite not significant for obstructive sleep apnea nor for conventional hypoventilatory patterns, strongly suggested initial respiratory failure, as lately confirmed by the pulmonary follow-up. We discuss the advantages of including sleep recording in the clinical work-up of patients affected by ALS.}, } @article {pmid38867220, year = {2024}, author = {Jia, Q and Song, Y and Zhang, C and Li, M and Feng, L and Sugimoto, K and Zhang, X and Liu, J and Gao, Y}, title = {Reasons and experience for patients with amyotrophic lateral sclerosis using traditional Chinese medicine: a CARE-TCM based mixed method study.}, journal = {BMC complementary medicine and therapies}, volume = {24}, number = {1}, pages = {231}, pmid = {38867220}, issn = {2662-7671}, support = {QN2021110001L//National Foreign Expert Project/ ; 2018, 12//Chinese Medicine Inheritance and Innovation Talent Project Leading Talent Support Program of National Traditional Chinese Medicine/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy ; *Medicine, Chinese Traditional/methods ; Female ; Male ; Middle Aged ; Surveys and Questionnaires ; Aged ; China ; Adult ; Quality of Life ; Qualitative Research ; }, abstract = {BACKGROUND AND AIM: Traditional Chinese medicine (TCM) is widely used by patients with amyotrophic lateral sclerosis (ALS). However, their reasons and experience in using TCM have received insufficient attention. Therefore, we conducted a mixed method study to gain insights into this issue.

MATERIALS AND METHODS: This study was conducted on the basis of the China Amyotrophic Lateral Sclerosis Registry of Patients with Traditional Chinese Medicine (CARE-TCM). Data were collected from Dongzhimen Hospital through a mixed method approach, including a questionnaire and a semi-structured interview. Patients with ALS who were using TCM when they were initially registered with CARE-TCM and who had been followed-up for over six months were recruited. The questionnaires' outcomes were statistically outlined, and the interview transcripts were thematically analysed to identify themes and sub-themes.

RESULTS: Fifty-two and sixteen patients were included in the questionnaire and semi-structured interview groups, respectively. Patients used TCM with the hope of regulating their body holistically to improve nonmotor symptoms and quality of life (QOL). Those who recognised TCM as ineffective tended to discontinue it after a three-month trial period. Although quality was a major concern, herbal medicine (HM) was the most frequently used modality among all participants (n = 52), with the majority (n = 44, 84.6%) continuing to use it. Patients emphasised in-person consultations as a crucial part of TCM treatment. However, the disability caused by disease often made this interaction unattainable.

CONCLUSION: Nonmotor symptoms and QOL hold substantial importance for patients with ALS using TCM. HM is a more suitable modality than other TCM treatment modalities, but patients are facing challenges in seeking HM treatment. It is necessary to promote the implementation of hierarchical diagnosis and treatment, thus making TCM more accessible.

TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04885374 (registered on May 13, 2021).}, } @article {pmid38866783, year = {2024}, author = {Di Timoteo, G and Giuliani, A and Setti, A and Biagi, MC and Lisi, M and Santini, T and Grandioso, A and Mariani, D and Castagnetti, F and Perego, E and Zappone, S and Lattante, S and Sabatelli, M and Rotili, D and Vicidomini, G and Bozzoni, I}, title = {M[6]A reduction relieves FUS-associated ALS granules.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {5033}, pmid = {38866783}, issn = {2041-1723}, support = {ERC-2019-SyG 855923-ASTRA//EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council)/ ; ERC-2018-CoG 818669-BrightEyes//EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council)/ ; AIRC IG 2019 Id. 23053//Associazione Italiana per la Ricerca sul Cancro (Italian Association for Cancer Research)/ ; PRIN 2017 2017P352Z4//Ministero dell'Istruzione, dell'Università e della Ricerca (Ministry of Education, University and Research)/ ; NextGenerationEU PNRR MUR//Ministero dell'Istruzione, dell'Università e della Ricerca (Ministry of Education, University and Research)/ ; "National Center for Gene Therapy and Drugbased on RNA Technology" (CN00000041)//Ministero dell'Istruzione, dell'Università e della Ricerca (Ministry of Education, University and Research)/ ; "National Center for Gene Therapy and Drug based on RNA Technology" (CN00000041)//Ministero dell'Istruzione, dell'Università e della Ricerca (Ministry of Education, University and Research)/ ; NextGenerationEU PNRR MUR//Ministero dell'Istruzione, dell'Università e della Ricerca (Ministry of Education, University and Research)/ ; "Sapienza" Ateneo Project 2021 n. RM12117A61C811CE//Sapienza Università di Roma (Sapienza University of Rome)/ ; Regione Lazio PROGETTI DI GRUPPI DI RICERCA 2020 - A0375-2020-36597//Regione Lazio (Region of Lazio)/ ; }, mesh = {*RNA-Binding Protein FUS/metabolism/genetics ; *Amyotrophic Lateral Sclerosis/metabolism/genetics/pathology ; Humans ; *Motor Neurons/metabolism/pathology ; *Induced Pluripotent Stem Cells/metabolism ; Cytoplasmic Granules/metabolism ; Fibroblasts/metabolism ; Adenosine/metabolism/analogs & derivatives ; Methyltransferases/metabolism/genetics ; Mutation ; Inclusion Bodies/metabolism ; Stress Granules/metabolism ; Transcriptome ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease due to gradual motoneurons (MN) degeneration. Among the processes associated to ALS pathogenesis, there is the formation of cytoplasmic inclusions produced by aggregation of mutant proteins, among which the RNA binding protein FUS. Here we show that, in neuronal cells and in iPSC-derived MN expressing mutant FUS, such inclusions are significantly reduced in number and dissolve faster when the RNA m[6]A content is diminished. Interestingly, stress granules formed in ALS conditions showed a distinctive transcriptome with respect to control cells, which reverted to similar to control after m[6]A downregulation. Notably, cells expressing mutant FUS were characterized by higher m[6]A levels suggesting a possible link between m[6]A homeostasis and pathological aggregates. Finally, we show that FUS inclusions are reduced also in patient-derived fibroblasts treated with STM-2457, an inhibitor of METTL3 activity, paving the way for its possible use for counteracting aggregate formation in ALS.}, } @article {pmid38865943, year = {2024}, author = {Ipek, L and Güneş Gencer, GY}, title = {Is caregiver burden of patients with amyotrophic lateral sclerosis related to caregivers' mindfulness, quality of life, and patients' functional level.}, journal = {Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia}, volume = {126}, number = {}, pages = {95-100}, doi = {10.1016/j.jocn.2024.06.007}, pmid = {38865943}, issn = {1532-2653}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/psychology/nursing/therapy ; Female ; *Quality of Life/psychology ; Male ; Middle Aged ; *Mindfulness ; *Caregiver Burden/psychology ; Adult ; Caregivers/psychology ; Aged ; Cost of Illness ; }, abstract = {BACKGROUND AND OBJECTIVE: The aim of this study was to evaluate the caregiver burden, mindfulness, and quality of life (QoL) of caregivers of ALS patients and the patient's functional level.

METHODS: This study was conducted with 57 ALS patients and their primary caregivers. The data were collected using the Zarit Burden Interview, Mindful Attention Awareness Scale (MAAS), the Short Form-36 (SF-36), and the ALS Functional Rating Scale (ALS-FRS).

RESULTS: The mean age of the caregivers was 49.7 ± 12 years; 66 % were female, and 73.7 % were spouses of the patients. Around 65 % of caregivers experienced a moderate to severe caregiver burden. A low and negative correlation was found between the caregiver burden and mindfulness of caregivers of ALS patients. As the mindfulness levels of the caregivers increased, the caregiver burden decreased, and the physical role difficulty score, one of the sub-dimensions of the QoL, increased. Also, caregivers' QoL decreased as caregiver burden increased (except physical function QoL, p < 0.05). Moreover, there was a positive correlation between the caregiver burden and ALSFRS-R scores (bulbar, motor, respiratory, and total) of the caregivers of ALS patients (p < 0.05).

DISCUSSION: Improved technology for managing ALS disease has increased patient life expectancy. However, caregivers may experience a high burden as the patient's functional level declines. Increasing caregiver mindfulness can help reduce the burden and improve their QoL.}, } @article {pmid38865034, year = {2024}, author = {Rashed, HR and Staff, NP and Milone, M and Mauermann, ML and Berini, S and Cheshire, WP and Coon, EA and Fealey, RD and Sorenson, E and Cutsforth-Gregory, J and Benarroch, EE and Sandroni, P and Low, PA and Singer, W and Shouman, K}, title = {Autonomic impairment in primary lateral sclerosis.}, journal = {Clinical autonomic research : official journal of the Clinical Autonomic Research Society}, volume = {34}, number = {4}, pages = {421-425}, pmid = {38865034}, issn = {1619-1560}, mesh = {Humans ; Male ; Middle Aged ; Female ; *Autonomic Nervous System Diseases/physiopathology/diagnosis/etiology ; Adult ; Retrospective Studies ; Aged ; Sweating/physiology ; Motor Neuron Disease/physiopathology/diagnosis/complications ; Autonomic Nervous System/physiopathology ; }, abstract = {PURPOSE: Prior studies reported evidence of autonomic involvement in motor neuron disease and suggested more severe dysfunction in upper motor neuron predominant syndromes. Hence, we sought to characterize autonomic impairment in primary lateral sclerosis.

METHODS: Neurological evaluations, thermoregulatory sweat tests, and autonomic reflex screens were analyzed retrospectively in 34 primary lateral sclerosis patients (28 definite and 6 probable). Patients with other potential causes of autonomic failure and patients with autonomic testing results compromised by artifact were excluded.

RESULTS: A total of 17 patients reported autonomic symptoms. Orthostatic lightheadedness was most frequent (8 patients), followed by bladder (7), bowel (5), and erectile dysfunction (3). The autonomic reflex screens of 33 patients were reviewed; 20 patients had abnormal studies. The thermoregulatory sweat tests of 19 patients were reviewed; 11 patients had abnormal studies. Composite Autonomic Severity Score was calculated for 33 patients and found abnormal in 20/33 patients (60.6%): 15/20 patients (75%) had mild impairment, and 5/20 patients (25%) had moderate impairment. The frequencies of testing abnormalities were: sudomotor 18/20 (90%), cardiovagal 9/20 (45%), and adrenergic 6/20 (30%). Sweat loss pattern analysis showed global, regional, and mixed patterns to be more common than length-dependent and distal patterns.

CONCLUSION: We found evidence of frequent autonomic dysfunction in primary lateral sclerosis, which is generally of modest severity akin to prior reports for amyotrophic lateral sclerosis, but more commonly in a pattern consistent with preganglionic/ganglionic localization. This suggests that primary lateral sclerosis, as with amyotrophic lateral sclerosis, is a multisystem disease that affects the autonomic nervous system.}, } @article {pmid38864944, year = {2024}, author = {Wang, LY and Zhang, L and Bai, XY and Qiang, RR and Zhang, N and Hu, QQ and Cheng, JZ and Yang, YL and Xiang, Y}, title = {The Role of Ferroptosis in Amyotrophic Lateral Sclerosis Treatment.}, journal = {Neurochemical research}, volume = {49}, number = {10}, pages = {2653-2667}, pmid = {38864944}, issn = {1573-6903}, mesh = {*Ferroptosis/drug effects/physiology ; *Amyotrophic Lateral Sclerosis/metabolism/drug therapy/pathology ; Humans ; Animals ; Oxidative Stress/physiology ; Reactive Oxygen Species/metabolism ; Iron/metabolism ; Antioxidants/therapeutic use ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a rare neurodegenerative disease with a challenging treatment landscape, due to its complex pathogenesis and limited availability of clinical drugs. Ferroptosis, an iron-dependent form of programmed cell death (PCD), stands distinct from apoptosis, necrosis, autophagy, and other cell death mechanisms. Recent studies have increasingly highlighted the role of iron deposition, reactive oxygen species (ROS) accumulation, oxidative stress, as well as systemic Xc- and glutamate accumulation in the antioxidant system in the pathogenesis of amyotrophic lateral sclerosis. Therefore, targeting ferroptosis emerges as a promising strategy for amyotrophic lateral sclerosis treatment. This review introduces the regulatory mechanism of ferroptosis, the relationship between amyotrophic lateral sclerosis and ferroptosis, and the drugs used in the clinic, then discusses the current status of amyotrophic lateral sclerosis treatment, hoping to provide new directions and targets for its treatment.}, } @article {pmid38863235, year = {2024}, author = {Priyanka, and Raymandal, B and Mondal, S}, title = {Native State Stabilization of Amyloidogenic Proteins by Kinetic Stabilizers: Inhibition of Protein Aggregation and Clinical Relevance.}, journal = {ChemMedChem}, volume = {19}, number = {19}, pages = {e202400244}, doi = {10.1002/cmdc.202400244}, pmid = {38863235}, issn = {1860-7187}, support = {SRG/2023/000434//Science and Engineering Research Board, India/ ; }, mesh = {Humans ; Kinetics ; *Amyloidogenic Proteins/metabolism/antagonists & inhibitors/chemistry ; Protein Aggregates/drug effects ; Superoxide Dismutase-1/metabolism/chemistry/antagonists & inhibitors ; Prealbumin/metabolism/chemistry/antagonists & inhibitors ; Amyloidosis/drug therapy/metabolism ; Clinical Relevance ; }, abstract = {Proteinopathies or amyloidoses are a group of life-threatening disorders that result from misfolding of proteins and aggregation into toxic insoluble amyloid aggregates. Amyloid aggregates have low clearance from the body due to the insoluble nature, leading to their deposition in various organs and consequent organ dysfunction. While amyloid deposition in the central nervous system leads to neurodegenerative diseases that mostly cause dementia and difficulty in movement, several other organs, including heart, liver and kidney are also affected by systemic amyloidoses. Regardless of the site of amyloid deposition, misfolding and structural alteration of the precursor proteins play the central role in amyloid formation. Kinetic stabilizers are an emerging class of drugs, which act like pharmacological chaperones to stabilize the native state structure of amyloidogenic proteins and to increase the activation energy barrier that is required for adopting a misfolded structure or conformation, ultimately leading to the inhibition of protein aggregation. In this review, we discuss the kinetic stabilizers that stabilize the native quaternary structure of transthyretin, immunoglobulin light chain and superoxide dismutase 1 that cause transthyretin amyloidoses, light chain amyloidosis and familial amyotrophic lateral sclerosis, respectively.}, } @article {pmid38862967, year = {2024}, author = {Vazquez-Sanchez, S and Tilkin, B and Gasset-Rosa, F and Zhang, S and Piol, D and McAlonis-Downes, M and Artates, J and Govea-Perez, N and Verresen, Y and Guo, L and Cleveland, DW and Shorter, J and Da Cruz, S}, title = {Frontotemporal dementia-like disease progression elicited by seeded aggregation and spread of FUS.}, journal = {Molecular neurodegeneration}, volume = {19}, number = {1}, pages = {46}, pmid = {38862967}, issn = {1750-1326}, mesh = {Animals ; Humans ; Mice ; Amyotrophic Lateral Sclerosis/pathology/metabolism ; Brain/metabolism/pathology ; Disease Models, Animal ; *Disease Progression ; *Frontotemporal Dementia/pathology/metabolism/genetics ; *Mice, Transgenic ; Protein Aggregation, Pathological/metabolism ; *RNA-Binding Protein FUS/metabolism/genetics ; }, abstract = {RNA binding proteins have emerged as central players in the mechanisms of many neurodegenerative diseases. In particular, a proteinopathy of fused in sarcoma (FUS) is present in some instances of familial Amyotrophic lateral sclerosis (ALS) and about 10% of sporadic Frontotemporal lobar degeneration (FTLD). Here we establish that focal injection of sonicated human FUS fibrils into brains of mice in which ALS-linked mutant or wild-type human FUS replaces endogenous mouse FUS is sufficient to induce focal cytoplasmic mislocalization and aggregation of mutant and wild-type FUS which with time spreads to distal regions of the brain. Human FUS fibril-induced FUS aggregation in the mouse brain of humanized FUS mice is accelerated by an ALS-causing FUS mutant relative to wild-type human FUS. Injection of sonicated human FUS fibrils does not induce FUS aggregation and subsequent spreading after injection into naïve mouse brains containing only mouse FUS, indicating a species barrier to human FUS aggregation and its prion-like spread. Fibril-induced human FUS aggregates recapitulate pathological features of FTLD including increased detergent insolubility of FUS and TAF15 and amyloid-like, cytoplasmic deposits of FUS that accumulate ubiquitin and p62, but not TDP-43. Finally, injection of sonicated FUS fibrils is shown to exacerbate age-dependent cognitive and behavioral deficits from mutant human FUS expression. Thus, focal seeded aggregation of FUS and further propagation through prion-like spread elicits FUS-proteinopathy and FTLD-like disease progression.}, } @article {pmid38861223, year = {2024}, author = {Parakh, S and Perri, ER and Vidal, M and Takalloo, Z and Jagaraj, CJ and Mehta, P and Yang, S and Thomas, CJ and Blair, IP and Hong, Y and Atkin, JD}, title = {Protein Disulfide Isomerase Endoplasmic Reticulum Protein 57 (ERp57) is Protective Against ALS-Associated Mutant TDP-43 in Neuronal Cells.}, journal = {Neuromolecular medicine}, volume = {26}, number = {1}, pages = {23}, pmid = {38861223}, issn = {1559-1174}, mesh = {*Protein Disulfide-Isomerases/genetics/metabolism ; *Amyotrophic Lateral Sclerosis/genetics/metabolism ; *DNA-Binding Proteins/genetics/metabolism ; Humans ; *Inclusion Bodies/metabolism/genetics ; Animals ; Mice ; Cell Nucleus/metabolism ; Cytoplasm/metabolism ; Neurons/metabolism/drug effects ; Superoxide Dismutase-1/genetics ; Mutation ; }, abstract = {Amyotrophic Lateral Sclerosis (ALS) is a severe neurodegenerative disease affecting motor neurons. Pathological forms of Tar-DNA binding protein-43 (TDP-43), involving its mislocalisation to the cytoplasm and the formation of misfolded inclusions, are present in almost all ALS cases (97%), and ~ 50% cases of the related condition, frontotemporal dementia (FTD), highlighting its importance in neurodegeneration. Previous studies have shown that endoplasmic reticulum protein 57 (ERp57), a member of the protein disulphide isomerase (PDI) family of redox chaperones, is protective against ALS-linked mutant superoxide dismutase (SOD1) in neuronal cells and transgenic SOD1[G93A] mouse models. However, it remains unclear whether ERp57 is protective against pathological TDP-43 in ALS. Here, we demonstrate that ERp57 is protective against key features of TDP-43 pathology in neuronal cells. ERp57 inhibited the mislocalisation of TDP-43[M337V] from the nucleus to the cytoplasm. In addition, ERp57 inhibited the number of inclusions formed by ALS-associated variant TDP-43[M337V] and reduced the size of these inclusions. ERp57 was also protective against ER stress and induction of apoptosis. Furthermore, ERp57 modulated the steady-state expression levels of TDP-43. This study therefore demonstrates a novel mechanism of action of ERp57 in ALS. It also implies that ERp57 may have potential as a novel therapeutic target to prevent the TDP-43 pathology associated with neurodegeneration.}, } @article {pmid38861034, year = {2024}, author = {Lehto, A and Schumacher, J and Kasper, E and Teipel, S and Hermann, A and Kurth, J and Krause, BJ and Prudlo, J}, title = {Cerebral glucose metabolic correlates of cognitive and behavioural impairments in amyotrophic lateral sclerosis.}, journal = {Journal of neurology}, volume = {271}, number = {8}, pages = {5290-5300}, pmid = {38861034}, issn = {1432-1459}, support = {13GW0482D//Bundesministerium für Bildung und Forschung/Verein Deutscher Ingenieure/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism/diagnostic imaging ; Male ; Female ; Middle Aged ; *Positron-Emission Tomography ; *Fluorodeoxyglucose F18/metabolism ; Aged ; *Glucose/metabolism ; *Neuropsychological Tests ; Magnetic Resonance Imaging ; Cognition Disorders/diagnostic imaging/metabolism/etiology ; Mental Disorders/metabolism/diagnostic imaging ; Brain/diagnostic imaging/metabolism ; Cerebral Cortex/diagnostic imaging/metabolism ; }, abstract = {OBJECTIVE: Half of ALS patients are cognitively and/or behaviourally impaired. As cognition/behaviour and cerebral glucose metabolism can be correlated by means of [18]F-Fluorodeoxyglucose positron emission tomography (FDG-PET), we aimed to utilise FDG-PET, first, to replicate group-level differences in glucose metabolism between non-demented ALS patients separated into non-impaired (ALSni), cognitively impaired (ALSci), behaviourally impaired (ALSbi), and cognitively and behaviourally impaired (ALScbi) groups; second, to investigate glucose metabolism and performance in various cognitive domains; and third, to examine the impact of partial volume effects correction (PVEC) of the FDG-PET data on the results.

METHODS: We analysed neuropsychological, clinical, and imaging data from 67 ALS patients (30 ALSni, 21 ALSci, 5 ALSbi, and 11 ALScbi). Cognition was assessed with the Edinburgh Cognitive and Behavioural ALS Screen, and two social cognition tests. FDG-PET and structural MRI scans were acquired for each patient. Voxel-based statistical analyses were undertaken on grey matter volume (GMV) and non-corrected vs. PVE-corrected FDG-PET scans.

RESULTS: ALSci and ALScbi had lower cognitive scores than ALSni. In contrast to both ALSni and ALSci, ALScbi showed widespread hypometabolism in the superior- and middle-frontal gyri in addition to the right temporal pole. Correlations were observed between the GMV, the FDG-PET signal, and various cognitive scores. The FDG-PET results were largely unaffected by PVEC.

INTERPRETATION: Our study identified widespread differences in hypometabolism in the ALScbi-ni but not in the ALSci-ni group comparison, raising the possibility that cerebral metabolism may be more closely related to the presence of behavioural changes than to mild cognitive deficits.}, } @article {pmid38860943, year = {2024}, author = {Zhang, Y and Xia, Y and Sun, J}, title = {Probiotics and microbial metabolites maintain barrier and neuromuscular functions and clean protein aggregation to delay disease progression in TDP43 mutation mice.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2363880}, pmid = {38860943}, issn = {1949-0984}, support = {I01 BX004824/BX/BLRD VA/United States ; R01 DK105118/DK/NIDDK NIH HHS/United States ; R01 DK114126/DK/NIDDK NIH HHS/United States ; R01 DK134343/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Humans ; Mice ; *Amyotrophic Lateral Sclerosis/metabolism/genetics/therapy ; Blood-Brain Barrier/metabolism ; Cytokines/metabolism ; Disease Models, Animal ; Disease Progression ; *DNA-Binding Proteins/metabolism/genetics ; *Gastrointestinal Microbiome ; Mice, Inbred C57BL ; Mice, Transgenic ; Mutation ; Neuroglia/metabolism ; *Probiotics/administration & dosage/pharmacology ; Spinal Cord/metabolism ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a neuromuscular disease. The ALS mice expressing human mutant of transactive response DNA binding protein of 43 kDa (hmTDP43) showed intestinal dysfunction before neuromuscular symptoms. We hypothesize that restoring the intestinal and microbial homeostasis with a bacterial metabolite or probiotics delays the ALS disease onset. We investigate the pathophysiological changes in the intestine and neurons, intestinal and blood-brain barriers, and inflammation during the ALS progression. We then cultured enteric glial cells (EGCs) isolated from TDP43 mice for mechanistic studies. TDP43 mice had significantly decreased intestinal mobility, increased permeability, and weakened muscle, compared with the age-matched wild-type mice. We observed increased hmTDP43 and Glial fibrillary acidic protein (GFAP), and decreased expression of α-smooth muscle actin (α-SMA), tight junction proteins (ZO-1 and Claudin-5) in the colon, spinal cord, and brain in TDP43 mice. TDP43 mice had reduced Butyryl-coenzyme A CoA transferase, decreased butyrate-producing bacteria Butyrivibrio fibrisolvens, and increased Bacteroides fragilis, compared to the WT mice. Serum inflammation cytokines (IL-6, IL-17, and IFN-γ) and LPS were elevated in TDP43 mice. EGCs from TDP43 mice showed aggregation of hmTDP43 associated with increased GFAP and ionized calcium-binding adaptor molecule (IBA1, a microglia marker). TDP43 mice treated with butyrate or probiotic VSL#3 had significantly increased rotarod time, increased intestinal mobility and decreased permeability, compared to the untreated group. Butyrate or probiotics treatment decreased the expression of GFAP, TDP43, and increased α-SMA, ZO-1, and Claudin-5 in the colon, spinal cord, and brain. Also, butyrate or probiotics treatment enhanced the Butyryl-coenzyme A CoA transferase, Butyrivibrio fibrisolvens, and reduced inflammatory cytokines in TDP43 mice. The TDP43 EGCs treated with butyrate or probiotics showed reduced GFAP, IBA1, and TDP43 aggregation. Restoring the intestinal and microbial homeostasis by beneficial bacteria and metabolites provide a potential therapeutic strategy to treat ALS.}, } @article {pmid38860430, year = {2024}, author = {Geng, Y and Liu, C and Xu, N and Suen, MC and Miao, H and Xie, Y and Zhang, B and Chen, X and Song, Y and Wang, Z and Cai, Q and Zhu, G}, title = {Crystal structure of a tetrameric RNA G-quadruplex formed by hexanucleotide repeat expansions of C9orf72 in ALS/FTD.}, journal = {Nucleic acids research}, volume = {52}, number = {13}, pages = {7961-7970}, pmid = {38860430}, issn = {1362-4962}, support = {32071188//National Scientific Foundation of China/ ; 16101120//Research Grants Council of the Hong Kong Special Administrative Region/ ; 3502Z20214001//Hong Kong University of Science and Technology/ ; 2021A1515220104//Guangdong Basic and Applied Basic Research Foundation/ ; }, mesh = {*C9orf72 Protein/genetics/chemistry ; *G-Quadruplexes ; *Amyotrophic Lateral Sclerosis/genetics ; *Frontotemporal Dementia/genetics ; Humans ; *RNA/chemistry/genetics ; *DNA Repeat Expansion/genetics ; Crystallography, X-Ray ; Models, Molecular ; }, abstract = {The abnormal GGGGCC hexanucleotide repeat expansions (HREs) in C9orf72 cause the fatal neurodegenerative diseases including amyotrophic lateral sclerosis and frontotemporal dementia. The transcribed RNA HREs, short for r(G4C2)n, can form toxic RNA foci which sequestrate RNA binding proteins and impair RNA processing, ultimately leading to neurodegeneration. Here, we determined the crystal structure of r(G4C2)2, which folds into a parallel tetrameric G-quadruplex composed of two four-layer dimeric G-quadruplex via 5'-to-5' stacking in coordination with a K+ ion. Notably, the two C bases locate at 3'- end stack on the outer G-tetrad with the assistance of two additional K+ ions. The high-resolution structure reported here lays a foundation in understanding the mechanism of neurological toxicity of RNA HREs. Furthermore, the atomic details provide a structural basis for the development of potential therapeutic agents against the fatal neurodegenerative diseases ALS/FTD.}, } @article {pmid38860134, year = {2024}, author = {Levison, LS and Jepsen, P and Andersen, H}, title = {Registration of Amyotrophic Lateral Sclerosis: Validity in the Danish National Patient Registry.}, journal = {Clinical epidemiology}, volume = {16}, number = {}, pages = {409-415}, pmid = {38860134}, issn = {1179-1349}, abstract = {PURPOSE: Health care databases are a valuable source for epidemiological research on amyotrophic lateral sclerosis (ALS) if diagnosis codes are valid. We evaluated the validity of the diagnostic codes for ALS in the Danish National Patient Registry (DNPR).

PATIENTS AND METHODS: We obtained data from the DNPR for all adult (>17 years) patients registered with ALS in Denmark between 1987 and 2022 (median population of 4.2 million during the study period). We randomly selected adult patients living in the North Denmark Region and Central Denmark Region (median population 1.4 million), with a primary discharge diagnosis code of ALS, diagnosed at three departments of neurology. We retrieved and reviewed medical records and estimated the positive predictive value (PPV) of the ALS diagnosis.

RESULTS: Over 36 years, we identified 5679 patients. From the validation cohort of 300 patients, we were able to retrieve 240 (80%) medical records, and 215 ALS diagnoses were confirmed. The overall positive predictive value was 89.6% (95% confidence interval (CI): 85.1-92.8). The highest PPV was achieved for diagnoses registered for patients aged ≥70 years (93.8; 95% CI: 86.2-97.3) compared to patients <60 years (83.4; 95% CI: 73.3-90.7).

CONCLUSION: We found a high PPV of primary diagnostic codes for ALS from Danish departments of neurology, demonstrating high validity. Thus, the DNPR is a well-suited data source for large-scale epidemiological research on ALS.}, } @article {pmid38859699, year = {2024}, author = {Finsterer, J and Strobl, W}, title = {Gastrointestinal involvement in neuromuscular disorders.}, journal = {Journal of gastroenterology and hepatology}, volume = {39}, number = {10}, pages = {1982-1993}, doi = {10.1111/jgh.16650}, pmid = {38859699}, issn = {1440-1746}, mesh = {Humans ; *Neuromuscular Diseases/complications/etiology ; *Gastrointestinal Diseases/etiology/therapy/diagnosis ; Myotonic Dystrophy/complications/diagnosis/physiopathology ; Mitochondrial Diseases/complications ; }, abstract = {Although not often discussed, many of the neuromuscular disorders (NMDs) affect the gastrointestinal tract (GIT). Depending on the type of NMD, the prevalence of GIT involvement ranges from <5% (e.g. hereditary neuropathies, myofibrillar myopathies) to 100% (e.g. MNGIE, OPMD). Particularly in NMDs with multisystem affection, involvement of the GIT can dominate the clinical presentation or at least make up a significant part of the clinical picture. The most prominent representatives of NMDs with multisystem involvement are the mitochondrial disorders (MIDs) and the myotonic dystrophies. The best known syndromic MIDs with GIT involvement are MNGIE, MELAS, Leigh, and Pearson syndromes. Among neuropathies, GIT involvement is most commonly found in ALS and GBS. GIT involvement may also be a feature of myasthenia. The clinical manifestations of GIT involvement are diverse and can affect the entire GIT, from the teeth to the rectum, including the liver and pancreas. The most well-known clinical manifestations of GIT involvement are dysphagia, nausea, vomiting, reflux, hollow organ dysmotility, hepatopathy, diabetes, diarrhea, constipation, and fecal incontinence. Even if treatment can usually only be symptomatic, the therapeutic options are diverse, are often effective, and can significantly and beneficially influence the course of the underlying NMD.}, } @article {pmid38859579, year = {2024}, author = {Meyer, T and Dreger, M and Grehl, T and Weyen, U and Kettemann, D and Weydt, P and Günther, R and Lingor, P and Petri, S and Koch, JC and Großkreutz, J and Rödiger, A and Baum, P and Hermann, A and Prudlo, J and Boentert, M and Weishaupt, JH and Löscher, WN and Dorst, J and Koc, Y and Bernsen, S and Cordts, I and Vidovic, M and Steinbach, R and Metelmann, M and Kleinveld, VE and Norden, J and Ludolph, A and Walter, B and Schumann, P and Münch, C and Körtvélyessy, P and Maier, A}, title = {Serum neurofilament light chain in distinct phenotypes of amyotrophic lateral sclerosis: A longitudinal, multicenter study.}, journal = {European journal of neurology}, volume = {31}, number = {9}, pages = {e16379}, pmid = {38859579}, issn = {1468-1331}, support = {//Bosis Canessa ALS Stiftung, Düsseldorf, Germany/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/blood ; *Neurofilament Proteins/blood ; Male ; Female ; Middle Aged ; *Phenotype ; Aged ; Longitudinal Studies ; Disease Progression ; Biomarkers/blood ; Adult ; Germany/epidemiology ; }, abstract = {OBJECTIVE: To assess the performance of serum neurofilament light chain (sNfL) in clinical phenotypes of amyotrophic lateral sclerosis (ALS).

METHODS: In 2949 ALS patients at 16 ALS centers in Germany and Austria, clinical characteristics and sNfL were assessed. Phenotypes were differentiated for two anatomical determinants: (1) upper and/or lower motor involvement (typical, typMN; upper/lower motor neuron predominant, UMNp/LMNp; primary lateral sclerosis, PLS) and (2) region of onset and propagation of motor neuron dysfunction (bulbar, limb, flail-arm, flail-leg, thoracic onset). Phenotypes were correlated to sNfL, progression, and survival.

RESULTS: Mean sNfL was - compared to typMN (75.7 pg/mL, n = 1791) - significantly lower in LMNp (45.1 pg/mL, n = 413), UMNp (58.7 pg/mL n = 206), and PLS (37.6 pg/mL, n = 84). Also, sNfL significantly differed in the bulbar (92.7 pg/mL, n = 669), limb (64.1 pg/mL, n = 1305), flail-arm (46.4 pg/mL, n = 283), flail-leg (53.6 pg/mL, n = 141), and thoracic (74.5 pg/mL, n = 96) phenotypes. Binary logistic regression analysis showed highest contribution to sNfL elevation for faster progression (odds ratio [OR] 3.24) and for the bulbar onset phenotype (OR 1.94). In contrast, PLS (OR 0.20), LMNp (OR 0.45), and thoracic onset (OR 0.43) showed reduced contributions to sNfL. Longitudinal sNfL (median 12 months, n = 2862) showed minor monthly changes (<0.2%) across all phenotypes. Correlation of sNfL with survival was confirmed (p < 0.001).

CONCLUSIONS: This study underscored the correlation of ALS phenotypes - differentiated for motor neuron involvement and region of onset/propagation - with sNfL, progression, and survival. These phenotypes demonstrated a significant effect on sNfL and should be recognized as independent confounders of sNfL analyses in ALS trials and clinical practice.}, } @article {pmid38857767, year = {2024}, author = {Bass, J and Hill, H and Jaworsky, C}, title = {Response to Hartman et al in reply to Bass et al's "Significant discordance in DermTech test results when paired with histopathology: Caveat emptor".}, journal = {Journal of the American Academy of Dermatology}, volume = {91}, number = {4}, pages = {e103}, doi = {10.1016/j.jaad.2024.06.003}, pmid = {38857767}, issn = {1097-6787}, mesh = {Humans ; *Dermoscopy ; Skin Neoplasms/pathology ; }, } @article {pmid38856890, year = {2024}, author = {Tripathi, S and Bhawana, }, title = {Epigenetic Orchestration of Neurodegenerative Disorders: A Possible Target for Curcumin as a Therapeutic.}, journal = {Neurochemical research}, volume = {49}, number = {9}, pages = {2319-2335}, pmid = {38856890}, issn = {1573-6903}, mesh = {*Curcumin/therapeutic use/pharmacology ; Humans ; *Epigenesis, Genetic/drug effects ; *Neurodegenerative Diseases/drug therapy/metabolism/genetics ; Animals ; *Neuroprotective Agents/therapeutic use/pharmacology ; Mitochondria/metabolism/drug effects ; Oxidative Stress/drug effects ; }, abstract = {Epigenetic modulations play a major role in gene expression and thus are responsible for various physiological changes including age-associated neurological disorders. Neurodegenerative diseases such as Alzheimer's (AD), Parkinson's (PD), Huntington's disease (HD), although symptomatically different, may share common underlying mechanisms. Most neurodegenerative diseases are associated with increased oxidative stress, aggregation of certain proteins, mitochondrial dysfunction, inactivation/dysregulation of protein degradation machinery, DNA damage and cell excitotoxicity. Epigenetic modulations has been reported to play a significant role in onset and progression of neurodegenerative diseases by regulating these processes. Previous studies have highlighted the marked antioxidant and neuroprotective abilities of polyphenols such as curcumin, by increased activity of detoxification systems like superoxide dismutase (SOD), catalase or glutathione peroxidase. The role of curcumin as an epigenetic modulator in neurological disorders and neuroinflammation apart from other chronic diseases have also been reported by a few groups. Nonetheless, the evidences for the role of curcumin mediated epigenetic modulation in its neuroprotective ability are still limited. This review summarizes the current knowledge of the role of mitochondrial dysfunction, epigenetic modulations and mitoepigenetics in age-associated neurological disorders such as PD, AD, HD, Amyotrophic Lateral Sclerosis (ALS), and Multiple Sclerosis (MS), and describes the neuroprotective effects of curcumin in the treatment and/or prevention of these neurodegenerative diseases by regulation of the epigenetic machinery.}, } @article {pmid38856805, year = {2024}, author = {Zhang, Z and He, X and Cui, J and Wang, J and Shi, B}, title = {Translation and reliability and validity of the Chinese version of Amyotrophic Lateral Sclerosis-Specific Quality of Life-Short Form.}, journal = {Journal of patient-reported outcomes}, volume = {8}, number = {1}, pages = {57}, pmid = {38856805}, issn = {2509-8020}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/psychology ; *Quality of Life/psychology ; Male ; Female ; Middle Aged ; Reproducibility of Results ; Cross-Sectional Studies ; China ; Surveys and Questionnaires ; Adult ; *Psychometrics/methods/instrumentation ; Translations ; Aged ; Translating ; }, abstract = {OBJECTIVE: To translate Amyotrophic Lateral Sclerosis-Specific Quality of Life-Short Form (ALSSQOL-SF) and test its reliability and validity, so that explore feasibility in Chinese mainland and make up the gap of specific tools for measuring quality of life of patients with ALS.

METHODS: This was a cross-sectional design. The Brislin translation model was used to translate ALSSQOL-SF, and the Chinese version of ALSSQOL-SF (C-ALSSQOL-SF) was revised through cultural adaptation and pre-test. The convenience sampling method was used to investigate 138 patients with ALS in Tianjin to test the reliability and validity of the C-ALSSQOL-SF.

RESULTS: The C-ALSSQOL-SF included 20 items, covering 6 dimensions: physical symptoms, bulbar function, negative emotion, interaction with people and the environment, religiosity and intimacy. The scale-level content validity index (S-CVI) of C-ALSSQOL-SF was 0.964, and the item-level content validity index (I-CVI) was between 0.857 to 1.000. The results of Confirmatory Factor Analysis (CFA) showed that CMIN/DF = 1.161, RMSEA = 0.034, GFI = 0.892, IFI = 0.976, TLI = 0.969, CFI = 0.975, and the 6-factor model fitted well. The scores of C-ALSSQOL-SF and WHOQOL-BREF were positively correlated (r = 0.745). The Cronbach's α coefficient of the scale was 0.85, the Cronbach's α coefficient of each dimension was between 0.59 to 0.86, and the split-half reliability was 0.78.

CONCLUSION: The Chinese version of ALSSQOL-SF has good reliability and validity, and can be used as a tool to evaluate the quality of life of patients with ALS in Chinese mainland.}, } @article {pmid38856793, year = {2025}, author = {Kumari, S and Kamiya, A and Karnik, SS and Rohilla, S and Dubey, SK and Taliyan, R}, title = {Novel Gene Therapy Approaches for Targeting Neurodegenerative Disorders: Focusing on Delivering Neurotrophic Genes.}, journal = {Molecular neurobiology}, volume = {62}, number = {1}, pages = {386-411}, pmid = {38856793}, issn = {1559-1182}, mesh = {Humans ; *Genetic Therapy/methods ; *Neurodegenerative Diseases/therapy/genetics ; Animals ; *Nerve Growth Factors/genetics ; Gene Transfer Techniques ; Genetic Vectors ; }, abstract = {Neurodegenerative illnesses (NDDs) like Alzheimer's, Parkinson's, amyotrophic lateral sclerosis, spinal muscular atrophy, and Huntington's disease have demonstrated considerable potential for gene therapy as a viable therapeutic intervention. NDDs are marked by the decline of neurons, resulting in changes in both behavior and pathology within the body. Strikingly, only symptomatic management is available without a cure for the NDDs. There is an unmet need for a permanent therapeutic approach. Many studies have been going on to target the newer therapeutic molecular targets for NDDs including gene-based therapy. Gene therapy has the potential to provide therapeutic benefits to a large number of patients with NDDs by offering mechanisms including neuroprotection, neuro-restoration, and rectification of pathogenic pathways. Gene therapy is a medical approach that aims to modify the biological characteristics of living cells by controlling the expression of specific genes in certain neurological disorders. Despite being the most complex and well-protected organ in the human body, there is clinical evidence to show that it is possible to specifically target the central nervous system (CNS). This provides hope for the prospective application of gene therapy in treating NDDs in the future. There are several advanced techniques available for using viral or non-viral vectors to deliver the therapeutic gene to the afflicted region. Neurotrophic factors (NTF) in the brain are crucial for the development, differentiation, and survival of neurons in the CNS, making them important in the context of various neurological illnesses. Gene delivery of NTF has the potential to be used as a therapeutic approach for the treatment of neurological problems in the brain. This review primarily focuses on the methodologies employed for delivering the genes of different NTFs to treat neurological disorders. These techniques are currently being explored as a viable therapeutic approach for neurodegenerative diseases. The article exclusively addresses gene delivery approaches and does not cover additional therapy strategies for NDDs. Gene therapy offers a promising alternative treatment for NDDs by stimulating neuronal growth instead of solely relying on symptom relief from drugs and their associated adverse effects. It can serve as a long-lasting and advantageous treatment choice for the management of NDDs. The likelihood of developing NDDs increases with age as a result of neuronal degradation in the brain. Gene therapy is an optimal approach for promoting neuronal growth through the introduction of nerve growth factor genes.}, } @article {pmid38855716, year = {2024}, author = {Morganroth, J and Bardakjian, TM and Dratch, L and Quinn, CC and Elman, LB}, title = {Enhancing Clinical Infrastructure for the Delivery of Intrathecal and Genetic Therapies: A Qalsody (Tofersen) Model for Patients With SOD1-ALS.}, journal = {Neurology. Clinical practice}, volume = {14}, number = {4}, pages = {e200303}, pmid = {38855716}, issn = {2163-0402}, abstract = {BACKGROUND: Qalsody (tofersen), an intrathecal therapy (IT) antisense oligonucleotide (ASO), was granted accelerated approval by the Food and Drug Administration for the treatment of SOD1-mediated amyotrophic lateral sclerosis (ALS) on April 25, 2023. Academic centers need to be prepared for expedited drug delivery. The purpose of this model was to predict the number of SOD1-ALS patients whom we expect to see at our center at the time of Qalsody approval and to use it to extrapolate to a model for a hypothetical sporadic IT ALS therapy.

RECENT FINDINGS: We predicted that 6 symptomatic and 14 presymptomatic SOD1 patients would come to our center, whereas a sporadic therapy would generate 108 patients, creating excess office visits, lumbar punctures, and genetic counseling visits.

IMPLICATIONS FOR PRACTICE: As new therapies for neurologic diseases come to market, preparing for increased office volume and complex drug delivery are essential for optimal care.}, } @article {pmid38855322, year = {2024}, author = {Tsekrekou, M and Giannakou, M and Papanikolopoulou, K and Skretas, G}, title = {Protein aggregation and therapeutic strategies in SOD1- and TDP-43- linked ALS.}, journal = {Frontiers in molecular biosciences}, volume = {11}, number = {}, pages = {1383453}, pmid = {38855322}, issn = {2296-889X}, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with severe socio-economic impact. A hallmark of ALS pathology is the presence of aberrant cytoplasmic inclusions composed of misfolded and aggregated proteins, including both wild-type and mutant forms. This review highlights the critical role of misfolded protein species in ALS pathogenesis, particularly focusing on Cu/Zn superoxide dismutase (SOD1) and TAR DNA-binding protein 43 (TDP-43), and emphasizes the urgent need for innovative therapeutic strategies targeting these misfolded proteins directly. Despite significant advancements in understanding ALS mechanisms, the disease remains incurable, with current treatments offering limited clinical benefits. Through a comprehensive analysis, the review focuses on the direct modulation of the misfolded proteins and presents recent discoveries in small molecules and peptides that inhibit SOD1 and TDP-43 aggregation, underscoring their potential as effective treatments to modify disease progression and improve clinical outcomes.}, } @article {pmid38854008, year = {2024}, author = {Rifai, OM and Waldron, FM and O'Shaughnessy, J and Read, FL and Gilodi, M and Pastore, A and Shneider, N and Tartaglia, GG and Zacco, E and Spence, H and Gregory, JM}, title = {Amygdala TDP-43 pathology is associated with behavioural dysfunction and ferritin accumulation in amyotrophic lateral sclerosis.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {38854008}, issn = {2692-8205}, support = {/WT_/Wellcome Trust/United Kingdom ; R01 NS127186/NS/NINDS NIH HHS/United States ; }, abstract = {BACKGROUND: Cognitive and behavioural symptoms associated with amyotrophic lateral sclerosis and frontotemporal spectrum disorders (ALSFTSD) are thought to be driven, at least in part, by the pathological accumulation of TDP-43.

METHODS: Here we examine post-mortem tissue from six brain regions associated with cognitive and behavioural symptoms in a cohort of 30 people with sporadic ALS (sALS), a proportion of which underwent standardized neuropsychological behavioural assessment as part of the Edinburgh Cognitive ALS Screen (ECAS).

RESULTS: Overall, the behavioural screen performed as part of the ECAS predicted accumulation of pathological phosphorylated TDP-43 (pTDP-43) with 100% specificity and 86% sensitivity in behaviour-associated brain regions. Notably, of these regions, pathology in the amygdala was the most predictive correlate of behavioural dysfunction in sALS. In the amygdala of sALS patients, we show variation in morphology, cell type predominance, and severity of pTDP-43 pathology. Further, we demonstrate that the presence and severity of intra-neuronal pTDP-43 pathology, but not astroglial pathology, or phosphorylated Tau pathology, is associated with behavioural dysfunction. Cases were also evaluated using a TDP-43 aptamer (TDP-43[APT]), which revealed that pathology was not only associated with behavioural symptoms, but also with ferritin levels, a measure of brain iron.

CONCLUSIONS: Intra-neuronal pTDP-43 and cytoplasmic TDP-43[APT] pathology in the amygdala is associated with behavioural symptoms in sALS. TDP-43[APT] staining intensity is also associated with increased ferritin, regardless of behavioural phenotype, suggesting that ferritin increases may occur upstream of clinical manifestation, in line with early TDP-43[APT] pathology, representing a potential region-specific imaging biomarker of early disease in ALS.}, } @article {pmid38853969, year = {2024}, author = {Bingham, IN and Norel, R and Roitberg, EG and Peller, J and Trevisan, MA and Agurto, C and Shalom, DE and Aguirre, F and Embon, I and Taitz, A and Harris, D and Wright, A and Seaver, K and Sullivan, S and Green, JR and Ostrow, LW and Fraenkel, E and Berry, JD}, title = {Listener effort quantifies clinically meaningful progression of dysarthria in people living with amyotrophic lateral sclerosis.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, pmid = {38853969}, support = {K24 DC016312/DC/NIDCD NIH HHS/United States ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative motor neuron disease that causes progressive muscle weakness. Progressive bulbar dysfunction causes dysarthria and thus social isolation, reducing quality of life. The Everything ALS Speech Study obtained longitudinal clinical information and speech recordings from 292 participants. In a subset of 120 participants, we measured speaking rate (SR) and listener effort (LE), a measure of dysarthria severity rated by speech pathologists from recordings. LE intra- and inter-rater reliability was very high (ICC 0.88 to 0.92). LE correlated with other measures of dysarthria at baseline. LE changed over time in participants with ALS (slope 0.77 pts/month; p<0.001) but not controls (slope 0.005 pts/month; p=0.807). The slope of LE progression was similar in all participants with ALS who had bulbar dysfunction at baseline, regardless of ALS site of onset. LE could be a remotely collected clinically meaningful clinical outcome assessment for ALS clinical trials.}, } @article {pmid38853922, year = {2024}, author = {Dilliott, AA and Costanzo, MC and Bandres-Ciga, S and Blauwendraat, C and Casey, B and Hoang, Q and Iwaki, H and Jang, D and Kim, JJ and Leonard, HL and Levine, KS and Makarious, M and Nguyen, TT and Rouleau, GA and Singleton, AB and Smadbeck, P and Solle, J and Vitale, D and Nalls, MA and Flannick, J and Burtt, NP and Farhan, SMK}, title = {The Neurodegenerative Disease Knowledge Portal: Propelling Discovery Through the Sharing of Neurodegenerative Disease Genomic Resources.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, pmid = {38853922}, abstract = {Although large-scale genetic association studies have proven useful for the delineation of neurodegenerative disease processes, we still lack a full understanding of the pathological mechanisms of these diseases, resulting in few appropriate treatment options and diagnostic challenges. To mitigate these gaps, the Neurodegenerative Disease Knowledge Portal (NDKP) was created as an open-science initiative with the aim to aggregate, enable analysis, and display all available genomic datasets of neurodegenerative disease, while protecting the integrity and confidentiality of the underlying datasets. The portal contains 218 genomic datasets, including genotyping and sequencing studies, of individuals across ten different phenotypic groups, including neurological conditions such as Alzheimer's disease, amyotrophic lateral sclerosis, Lewy body dementia, and Parkinson's disease. In addition to securely hosting large genomic datasets, the NDKP provides accessible workflows and tools to effectively utilize the datasets and assist in the facilitation of customized genomic analyses. Here, we summarize the genomic datasets currently included within the portal, the bioinformatics processing of the datasets, and the variety of phenotypes captured. We also present example use-cases of the various user interfaces and integrated analytic tools to demonstrate their extensive utility in enabling the extraction of high-quality results at the source, for both genomics experts and those in other disciplines. Overall, the NDKP promotes open-science and collaboration, maximizing the potential for discovery from the large-scale datasets researchers and consortia are expending immense resources to produce and resulting in reproducible conclusions to improve diagnostic and therapeutic care for neurodegenerative disease patients.}, } @article {pmid38853763, year = {2024}, author = {Maranzano, A and Verde, F and Dubini, A and Torre, S and Colombo, E and Doretti, A and Gentile, F and Manini, A and Milone, I and Brusati, A and Peverelli, S and Santangelo, S and Spinelli, EG and Torresani, E and Gentilini, D and Messina, S and Morelli, C and Poletti, B and Agosta, F and Ratti, A and Filippi, M and Silani, V and Ticozzi, N}, title = {Association of APOE genotype and cerebrospinal fluid Aβ and tau biomarkers with cognitive and motor phenotype in amyotrophic lateral sclerosis.}, journal = {European journal of neurology}, volume = {31}, number = {9}, pages = {e16374}, pmid = {38853763}, issn = {1468-1331}, support = {RF-2021-12374238//Ministry of Health/ ; }, mesh = {Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; *Amyloid beta-Peptides/cerebrospinal fluid ; *Amyotrophic Lateral Sclerosis/cerebrospinal fluid/genetics ; *Apolipoproteins E/genetics/cerebrospinal fluid ; *Biomarkers/cerebrospinal fluid ; Cognition Disorders/cerebrospinal fluid/genetics/etiology ; Genotype ; Peptide Fragments/cerebrospinal fluid ; *Phenotype ; *tau Proteins/cerebrospinal fluid ; }, abstract = {OBJECTIVE: Little is known about amyotrophic lateral sclerosis (ALS)-nonspecific cognitive deficits - most notably memory disturbance - and their biological underpinnings. We investigated the associations of the Alzheimer's disease (AD) genetic risk factor APOE and cerebrospinal fluid (CSF) biomarkers Aβ and tau proteins with cognitive and motor phenotype in ALS.

METHODS: APOE haplotype was determined in 281 ALS patients; for 105 of these, CSF levels of Aβ42, Aβ40, total tau (T-tau), and phosphorylated tau (P-tau181) were quantified by chemiluminescence enzyme immunoassay (CLEIA). The Edinburgh Cognitive and Behavioural ALS Screen (ECAS) was employed to evaluate the neuropsychological phenotype.

RESULTS: APOE-E4 allele was associated with worse ECAS memory score (median, 14.0 in carriers vs. 16.0 in non-carriers) and lower CSF Aβ42 (-0.8 vs. 0.1, log-transformed values) and Aβ42/40 ratio (-0.1 vs. 0.3). Some 37.1% of ALS patients showed low Aβ42 levels, possibly reflecting cerebral Aβ deposition. While lower Aβ42/40 correlated with lower memory score (β = 0.20), Aβ42 positively correlated with both ALS-specific (β = 0.24) and ALS-nonspecific (β = 0.24) scores. Although Aβ42/40 negatively correlated with T-tau (β = -0.29) and P-tau181 (β = -0.33), we found an unexpected positive association of Aβ42 and Aβ40 with both tau proteins. Regarding motor phenotype, lower levels of Aβ species were associated with lower motor neuron (LMN) signs (Aβ40: β = 0.34; Aβ42: β = 0.22).

CONCLUSIONS: APOE haplotype and CSF Aβ biomarkers are associated with cognitive deficits in ALS and particularly with memory impairment. This might partly reflect AD-like pathophysiological processes, but additional ALS-specific mechanisms could be involved.}, } @article {pmid38853167, year = {2024}, author = {Öijerstedt, L and Foucher, J and Lovik, A and Yazdani, S and Juto, A and Kläppe, U and Fang, F and Ingre, C}, title = {Repeated cognitive assessments show stable function over time in patients with ALS.}, journal = {Journal of neurology}, volume = {271}, number = {8}, pages = {5267-5274}, pmid = {38853167}, issn = {1432-1459}, support = {SLS-986189//Svenska Läkaresällskapet/ ; 2023-02428//Vetenskapsrådet/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology/diagnosis/complications ; Male ; Female ; Middle Aged ; Aged ; *Cognitive Dysfunction/etiology/physiopathology/diagnosis ; Longitudinal Studies ; *Neuropsychological Tests ; Disease Progression ; Executive Function/physiology ; Sweden/epidemiology ; Follow-Up Studies ; Adult ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a multisystem disorder with not only motor symptoms but also extra-motor features including cognitive impairment. The most common cognitive profile observed in patients with ALS includes deficits in executive function, language, and social cognition. However, longitudinal studies on cognitive changes over time in ALS are sparse. We aimed to investigate the presence and nature of cognitive impairment at the time of ALS diagnosis and its association with survival as well as explore longitudinal cognitive change.

METHOD: Patients (n = 216) were recruited at the Karolinska University Hospital in Stockholm, Sweden. Follow-up visits (n = 307 in total) were performed every 6 months. Cognitive impairment was assessed using the Edinburgh Cognitive and Behavioural ALS Screen (ECAS) and/or Montreal Cognitive Assessment (MoCA).

RESULTS: Cognitive impairment was observed in 38% of the patients at the time of ALS diagnosis, and the majority of these patients had deficits in executive function and/or language. Patients with cognitive impairment at the time of diagnosis had a more rapid decline in ALSFRS-R at 12- and 18-months follow-up, and a shorter survival. Cognitive function was stable during the first 2 years after diagnosis, and did not follow the trajectories of decline in motor functions.

CONCLUSION: Cognitive impairment in ALS was associated with a faster decline of motor functions, and shorter survival. However, cognitive function did not deteriorate over time. Cognitive assessment is essential for the patients and caregivers to understand the phenotypic expression of ALS.}, } @article {pmid38852806, year = {2024}, author = {Yazdani, S and Lovik, A and Seitz, C and Ingre, C and Fang, F and Andersson, J}, title = {T cell subset composition differs between blood and cerebrospinal fluid in amyotrophic lateral sclerosis.}, journal = {Clinical immunology (Orlando, Fla.)}, volume = {265}, number = {}, pages = {110270}, doi = {10.1016/j.clim.2024.110270}, pmid = {38852806}, issn = {1521-7035}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/cerebrospinal fluid/immunology/blood ; Male ; Female ; Middle Aged ; *Flow Cytometry ; Aged ; *T-Lymphocyte Subsets/immunology ; Adult ; }, abstract = {Inflammation is a hallmark of amyotrophic lateral sclerosis (ALS) and is often assessed through biological samples. Due to the easier access, peripheral blood is more commonly phenotyped instead of cerebrospinal fluid (CSF) or affected tissues in ALS. Here, using flow cytometry, we compared the composition of T cell subsets in blood and CSF in ALS patients. We found consistent but weak correlations between blood and CSF for all T cell subsets examined. This finding implies that blood and CSF offer complementary information when characterizing T cell immunity in ALS and blood may not be used as a surrogate for CSF.}, } @article {pmid38852741, year = {2024}, author = {Moncayo, AK and Grossman, D and Kim, CC and Hartman, RI}, title = {Response to Bass et al's "Significant discordance in DermTech test results when paired with histopathology: Caveat emptor".}, journal = {Journal of the American Academy of Dermatology}, volume = {91}, number = {4}, pages = {e101-e102}, doi = {10.1016/j.jaad.2024.05.079}, pmid = {38852741}, issn = {1097-6787}, mesh = {Humans ; *Skin Neoplasms/pathology ; Dermoscopy ; Melanoma/pathology ; }, } @article {pmid38852112, year = {2024}, author = {Leighton, DJ and Ansari, M and Newton, J and Cleary, E and Stephenson, L and Beswick, E and Carod Artal, J and Davenport, R and Duncan, C and Gorrie, GH and Morrison, I and Swingler, R and Deary, IJ and Porteous, M and Chandran, S and Pal, S and , }, title = {Genotypes and phenotypes of motor neuron disease: an update of the genetic landscape in Scotland.}, journal = {Journal of neurology}, volume = {271}, number = {8}, pages = {5256-5266}, pmid = {38852112}, issn = {1432-1459}, support = {CAF/MND/15/01//Chief Scientist Office, Scottish Government Health and Social Care Directorate/ ; CAF/MND/15/01//MND Scotland/ ; CAF/MND/15/01/MNDA_/Motor Neurone Disease Association/United Kingdom ; }, mesh = {Humans ; Scotland/epidemiology ; *Motor Neuron Disease/genetics/epidemiology ; Male ; Female ; Middle Aged ; Aged ; *Phenotype ; *C9orf72 Protein/genetics ; Genotype ; Adult ; DNA Repeat Expansion/genetics ; Cohort Studies ; Aged, 80 and over ; Superoxide Dismutase-1/genetics ; }, abstract = {BACKGROUND: Using the Clinical Audit Research and Evaluation of Motor Neuron Disease (CARE-MND) database and the Scottish Regenerative Neurology Tissue Bank, we aimed to outline the genetic epidemiology and phenotypes of an incident cohort of people with MND (pwMND) to gain a realistic impression of the genetic landscape and genotype-phenotype associations.

METHODS: Phenotypic markers were identified from the CARE-MND platform. Sequence analysis of 48 genes was undertaken. Variants were classified using a structured evidence-based approach. Samples were also tested for C9orf72 hexanucleotide expansions using repeat-prime PCR methodology.

RESULTS: 339 pwMND donated a DNA sample: 44 (13.0%) fulfilled criteria for having a pathogenic variant/repeat expansion, 53.5% of those with a family history of MND and 9.3% of those without. The majority (30 (8.8%)) had a pathogenic C9orf72 repeat expansion, including two with intermediate expansions. Having a C9orf72 expansion was associated with a significantly lower Edinburgh Cognitive and Behavioural ALS Screen ALS-Specific score (p = 0.0005). The known pathogenic SOD1 variant p.(Ile114Thr), frequently observed in the Scottish population, was detected in 9 (2.7%) of total cases but in 17.9% of familial cases. Rare variants were detected in FUS and NEK1. One individual carried both a C9orf72 expansion and SOD1 variant.

CONCLUSIONS: Our results provide an accurate summary of MND demographics and genetic epidemiology. We recommend early genetic testing of people with cognitive impairment to ensure that C9orf72 carriers are given the best opportunity for informed treatment planning. Scotland is enriched for the SOD1 p.(Ile114Thr) variant and this has significant implications with regards to future genetically-targeted treatments.}, } @article {pmid38851229, year = {2024}, author = {Yu, Y and Zeng, L and Wu, M and Li, C and Qiu, Y and Liu, J and Yang, F and Xia, P}, title = {Exploring amyotrophic lateral sclerosis patients' experiences of psychological distress during the disease course in China: a qualitative study.}, journal = {BMJ open}, volume = {14}, number = {6}, pages = {e082398}, pmid = {38851229}, issn = {2044-6055}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/psychology ; Female ; Male ; China ; Middle Aged ; *Qualitative Research ; *Psychological Distress ; *Quality of Life ; Adult ; Aged ; Stress, Psychological/psychology ; Interviews as Topic ; Social Stigma ; Adaptation, Psychological ; }, abstract = {OBJECTIVE: This study aims to explore the psychological distress course of Chinese amyotrophic lateral sclerosis (ALS) patients after the onset of the disease and to provide targeted nursing guidance.

DESIGN: The interview content was analysed qualitatively. We used seven steps of Colaizzi's method to analyse the participants' data.

SETTING: Wuhan, China, Traditional Chinese Medicine Hospital.

PARTICIPANTS: A semistructured face-to-face interview were performed among 22 people with ALS from the motor neuron disease rehabilitation centre of a tertiary Chinese medicine hospital in China.

RESULT: This study included a total of 22 participants, from whom three main themes regarding the psychological distress trajectory of ALS patients were extracted from the interview data: 'Time begins to run out' include tormented and restless waiting and shock and doubt in ALS disease confirmation, 'Family out of control' include the burden of stigma and function loss, the burden of missing family roles, the burden of marriage's emotional needs and the burden of offspring health, 'Way forward' include struggle between live and death and struggle between quality of life and the value of life.

CONCLUSION: This study outlines the psychologically distressing journey of ALS patients. Studies have pointed out the need for targeted care to address patients' various sources of psychological distress to improve their quality of life and coping ability, increase their psychological resilience and reconstruct their life beliefs.}, } @article {pmid38850875, year = {2024}, author = {Coen, M and Benyamine, A and Delmont, E and Kaplanski, G and Bouabdallah, R and Xerri, L and Attarian, S and Serratrice, J}, title = {Tell-tale immune-related neurological syndromes: Should we look for and underlying low-grade B-cell lymphoma? A retrospective study on 12 cases.}, journal = {Pathology, research and practice}, volume = {260}, number = {}, pages = {155377}, doi = {10.1016/j.prp.2024.155377}, pmid = {38850875}, issn = {1618-0631}, mesh = {Humans ; Retrospective Studies ; Male ; Female ; Middle Aged ; *Lymphoma, B-Cell/pathology/immunology ; Aged ; Adult ; }, abstract = {INTRODUCTION: Immune-related neurological syndromes (affecting both the central and peripheral nervous system, as well as the neuromuscular junction) can associate with low-grade B-cell lymphomas.

METHODS: We conducted a retrospective study on the records of patients with miscellaneous immune-related neuropathies followed by the "Referral Centre for Neuromuscular Diseases and ALS" in collaboration with the Services of Internal Medicine and Hematology (La Timone Hospital, and the Paoli Calmettes-Insitute, Marseille, France; Geneva University Hospitals, Geneva, Switzerland). Clinical, biological, immunological and histological work-up was carried out and data collected.

RESULTS: We identified 12 patients with neurological syndromes and atypical presentation/course. In all these patients multiple autoantibodies were found. This prompted us to perform thorough hematologic investigations, that led to the diagnosis of different type of Low-Grade B-Cell lymphomas [i.e. marginal zone lymphomas with lymphoplasmacytic differentiation (n=3), splenic marginal area lymphoma with secondary lymph node invasion (n=1), unclassified marginal area lymphomas (n=8)]. Treatment of the underling lymphoma resulted in an improvement (n=8) or stabilization (n=4) of neurological disease.

CONCLUSION: Atypical presentation of immune-related neurological syndromes, as well as the presence of antibodies with different antigenic targets should be regarded as "warning signs" and raise the suspicion of a paraneoplastic origin sustained by an underlying low-grade B-cell lymphoma that should be actively sought and treated. Close collaboration between internists, neurologists and hematologists allows for the appropriate management of each case.}, } @article {pmid38849544, year = {2024}, author = {Sun, H and Yang, B and Li, Q and Zhu, X and Song, E and Liu, C and Song, Y and Jiang, G}, title = {Polystyrene nanoparticles trigger aberrant condensation of TDP-43 and amyotrophic lateral sclerosis-like symptoms.}, journal = {Nature nanotechnology}, volume = {19}, number = {9}, pages = {1354-1365}, pmid = {38849544}, issn = {1748-3395}, support = {22176206, 22174116 and 22241604//National Natural Science Foundation of China (National Science Foundation of China)/ ; }, mesh = {*Polystyrenes/chemistry/toxicity ; *Amyotrophic Lateral Sclerosis/metabolism/chemically induced ; *DNA-Binding Proteins/metabolism ; Humans ; *Nanoparticles/chemistry ; Animals ; Mice ; Oxidative Stress/drug effects ; Motor Neurons/metabolism/drug effects/pathology ; HSP70 Heat-Shock Proteins/metabolism ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the dysfunction and progressive death of cerebral and spinal motor neurons. Preliminary epidemiological research has hinted at a relationship between environmental risks and the escalation of ALS, but the underlying reasons remain mostly mysterious. Here we show that nanosize polystyrene plastics (PS) induce ALS-like symptoms and illustrate the related molecular mechanism. When exposed to PS, cells endure internal oxidative stress, which leads to the aggregation of TAR DNA-binding protein 43 kDa (TDP-43), triggering ALS-like characteristics. In addition, the oxidized heat shock protein 70 fails to escort TDP-43 back to the nucleus. The cytoplasmic accumulation of TDP-43 facilitates the formation of a complex between PS and TDP-43, enhancing the condensation and solidification of TDP-43. These findings are corroborated through in silico and in vivo assays. Altogether, our work illustrates a unique toxicological mechanism induced by nanoparticles and provides insights into the connection between environmental pollution and neurodegenerative disorders.}, } @article {pmid38849367, year = {2024}, author = {Mora, S and Stuckert, A and von Huth Friis, R and Pietersz, K and Noes-Holt, G and Montañana-Rosell, R and Wang, H and Sørensen, AT and Selvan, R and Verhaagen, J and Allodi, I}, title = {Stabilization of V1 interneuron-motor neuron connectivity ameliorates motor phenotype in a mouse model of ALS.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {4867}, pmid = {38849367}, issn = {2041-1723}, support = {21-2B-9477/L102 and 18-2B-3570//Aage og Johanne Louis-Hansens Fond (Aage and Johanne Louis-Hansen Foundation)/ ; }, mesh = {Animals ; *Amyotrophic Lateral Sclerosis/genetics/physiopathology/metabolism/therapy ; *Interneurons/metabolism ; *Motor Neurons/metabolism ; *Disease Models, Animal ; Mice ; *Mice, Transgenic ; *Synapses/metabolism ; Phenotype ; Male ; Genetic Therapy/methods ; Humans ; Female ; Superoxide Dismutase-1/genetics/metabolism ; }, abstract = {Loss of connectivity between spinal V1 inhibitory interneurons and motor neurons is found early in disease in the SOD1[G93A] mice. Such changes in premotor inputs can contribute to homeostatic imbalance of motor neurons. Here, we show that the Extended Synaptotagmin 1 (Esyt1) presynaptic organizer is downregulated in V1 interneurons. V1 restricted overexpression of Esyt1 rescues inhibitory synapses, increases motor neuron survival, and ameliorates motor phenotypes. Two gene therapy approaches overexpressing ESYT1 were investigated; one for local intraspinal delivery, and the other for systemic administration using an AAV-PHP.eB vector delivered intravenously. Improvement of motor functions is observed in both approaches, however systemic administration appears to significantly reduce onset of motor impairment in the SOD1[G93A] mice in absence of side effects. Altogether, we show that stabilization of V1 synapses by ESYT1 overexpression has the potential to improve motor functions in ALS, demonstrating that interneurons can be a target to attenuate ALS symptoms.}, } @article {pmid38849340, year = {2024}, author = {Caldi Gomes, L and Hänzelmann, S and Hausmann, F and Khatri, R and Oller, S and Parvaz, M and Tzeplaeff, L and Pasetto, L and Gebelin, M and Ebbing, M and Holzapfel, C and Columbro, SF and Scozzari, S and Knöferle, J and Cordts, I and Demleitner, AF and Deschauer, M and Dufke, C and Sturm, M and Zhou, Q and Zelina, P and Sudria-Lopez, E and Haack, TB and Streb, S and Kuzma-Kozakiewicz, M and Edbauer, D and Pasterkamp, RJ and Laczko, E and Rehrauer, H and Schlapbach, R and Carapito, C and Bonetto, V and Bonn, S and Lingor, P}, title = {Multiomic ALS signatures highlight subclusters and sex differences suggesting the MAPK pathway as therapeutic target.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {4893}, pmid = {38849340}, issn = {2041-1723}, support = {01GM1917A//Bundesministerium für Bildung und Forschung (Federal Ministry of Education and Research)/ ; SFB1192 PB8, and PC3//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/genetics/drug therapy/metabolism ; Humans ; Female ; Animals ; Male ; Mice ; *Mice, Transgenic ; *MAP Kinase Signaling System/drug effects ; *Disease Models, Animal ; Pyridones/pharmacology/therapeutic use ; RNA-Binding Protein FUS/metabolism/genetics ; Prefrontal Cortex/metabolism ; Transcriptome ; Superoxide Dismutase-1/genetics/metabolism ; DNA-Binding Proteins/metabolism/genetics ; Middle Aged ; MicroRNAs/genetics/metabolism ; C9orf72 Protein/genetics/metabolism ; Sex Characteristics ; Aged ; Sex Factors ; Pyrimidinones ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a debilitating motor neuron disease and lacks effective disease-modifying treatments. This study utilizes a comprehensive multiomic approach to investigate the early and sex-specific molecular mechanisms underlying ALS. By analyzing the prefrontal cortex of 51 patients with sporadic ALS and 50 control subjects, alongside four transgenic mouse models (C9orf72-, SOD1-, TDP-43-, and FUS-ALS), we have uncovered significant molecular alterations associated with the disease. Here, we show that males exhibit more pronounced changes in molecular pathways compared to females. Our integrated analysis of transcriptomes, (phospho)proteomes, and miRNAomes also identified distinct ALS subclusters in humans, characterized by variations in immune response, extracellular matrix composition, mitochondrial function, and RNA processing. The molecular signatures of human subclusters were reflected in specific mouse models. Our study highlighted the mitogen-activated protein kinase (MAPK) pathway as an early disease mechanism. We further demonstrate that trametinib, a MAPK inhibitor, has potential therapeutic benefits in vitro and in vivo, particularly in females, suggesting a direction for developing targeted ALS treatments.}, } @article {pmid38848664, year = {2024}, author = {Morioka, D and Sagisaka, R and Nakagawa, K and Takahashi, H and Tanaka, H}, title = {Effect of timing of advanced life support on out-of-hospital cardiac arrests at home.}, journal = {The American journal of emergency medicine}, volume = {82}, number = {}, pages = {94-100}, doi = {10.1016/j.ajem.2024.05.021}, pmid = {38848664}, issn = {1532-8171}, mesh = {Humans ; *Out-of-Hospital Cardiac Arrest/therapy/mortality ; Male ; Female ; Retrospective Studies ; Aged ; *Epinephrine/administration & dosage/therapeutic use ; Japan/epidemiology ; Middle Aged ; *Emergency Medical Services ; *Advanced Cardiac Life Support/methods ; Intubation, Intratracheal/statistics & numerical data ; Time-to-Treatment/statistics & numerical data ; Aged, 80 and over ; Registries ; Time Factors ; Return of Spontaneous Circulation ; Cardiopulmonary Resuscitation/methods ; }, abstract = {AIM: In cases of out-of-hospital cardiac arrests (OHCA) occurring at home, Japanese emergency medical services personnel decide whether to provide treatment on the scene or during transport based on their judgment. This study aimed to evaluate the association between the timing of advanced life support (ALS) (i.e., endotracheal intubation [ETI] or adrenaline administration) for OHCA at home and prognosis.

METHOD: This retrospective cohort study used data from the Japan Utstein Registry and emergency transport data collected from patients who underwent pre-hospital ETI (n = 6806) and received adrenaline (n = 22,636) between 2016 and 2019. The timing of ETI or adrenaline administration was determined as "on the scene" or "in the ambulance." Multiple logistic regression analysis was used to estimate the association among the timing of ALS implementation, pre-hospital return of spontaneous circulation (ROSC), and survival at 1 month.

RESULT: ETI on the scene was significantly positively associated with pre-hospital ROSC (adjusted odds ratio [AOR], 1.81; 95% confidence interval [CI], 1.57-2.09) and survival at 1 month (AOR, 1.81; 95% CI, 1.47-2.23). Adrenaline administration on the scene was significantly positively associated with pre-hospital ROSC (AOR, 2.51; 95% CI, 2.33-2.70) and survival at 1 month (AOR, 2.13; 95% CI, 1.89-2.40).

CONCLUSION: Our analysis suggests performing ALS on the scene was associated with pre-hospital ROSC and survival at 1 month. Further efforts are needed to increase the rate of ALS implementation on the scene by emergency life-saving technicians.}, } @article {pmid38848044, year = {2025}, author = {Samalia, P and Niederer, R}, title = {Letter to the Editor: Comment on Raad et al's "Adalimumab for the Treatment of Non-Infectious Uveitis: A Real Life Experience".}, journal = {Ocular immunology and inflammation}, volume = {33}, number = {3}, pages = {377}, doi = {10.1080/09273948.2024.2362879}, pmid = {38848044}, issn = {1744-5078}, } @article {pmid38848023, year = {2024}, author = {Fabi, JP}, title = {The connection between gut microbiota and its metabolites with neurodegenerative diseases in humans.}, journal = {Metabolic brain disease}, volume = {39}, number = {5}, pages = {967-984}, doi = {10.1007/s11011-024-01369-w}, pmid = {38848023}, issn = {1573-7365}, support = {2013/07914-8//Fundação de Amparo à Pesquisa do Estado de São Paulo/ ; 307842/2022-3//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Neurodegenerative Diseases/metabolism/microbiology ; *Dysbiosis/metabolism ; *Brain-Gut Axis/physiology ; Animals ; Blood-Brain Barrier/metabolism ; Brain/metabolism ; }, abstract = {The aging of populations is a global phenomenon that follows a possible increase in the incidence of neurodegenerative diseases. Alzheimer's, Parkinson's, Multiple Sclerosis, Amyotrophic Lateral Sclerosis, and Huntington's diseases are some neurodegenerative disorders that aging could initiate or aggravate. Recent research has indicated that intestinal microbiota dysbiosis can trigger metabolism and brain functioning, contributing to the etiopathogenesis of those neurodegenerative diseases. The intestinal microbiota and its metabolites show significant functions in various aspects, such as the immune system modulation (development and maturation), the maintenance of the intestinal barrier integrity, the modulation of neuromuscular functions in the intestine, and the facilitation of essential metabolic processes for both the microbiota and humans. The primary evidence supporting the connection between intestinal microbiota and its metabolites with neurodegenerative diseases are epidemiological observations and animal models experimentation. This paper reviews up-to-date evidence on the correlation between the microbiota-gut-brain axis and neurodegenerative diseases, with a specially focus on gut metabolites. Dysbiosis can increase inflammatory cytokines and bacterial metabolites, altering intestinal and blood-brain barrier permeability and causing neuroinflammation, thus facilitating the pathogenesis of neurodegenerative diseases. Clinical data supporting this evidence still needs to be improved. Most of the works found are descriptive and associated with the presence of phyla or species of bacteria with neurodegenerative diseases. Despite the limitations of recent research, the potential for elucidating clinical questions that have thus far eluded clarification within prevailing pathophysiological frameworks of health and disease is promising through investigation of the interplay between the host and microbiota.}, } @article {pmid38847583, year = {2024}, author = {Zhou, M and Sheng, Z and Ji, G and Zhang, X}, title = {Aerogel-Involved Triple-State Gels Resemble Natural Living Leaves in Structure and Multi-Functions.}, journal = {Advanced materials (Deerfield Beach, Fla.)}, volume = {36}, number = {32}, pages = {e2406007}, doi = {10.1002/adma.202406007}, pmid = {38847583}, issn = {1521-4095}, support = {52173052//National Natural Science Foundation of China/ ; SYC2022125//Suzhou Municipal Science and Technology Bureau/ ; }, mesh = {*Plant Leaves/chemistry/metabolism ; Gels/chemistry ; Silicon Dioxide/chemistry ; Hydrogels/chemistry ; Photosynthesis ; Polyvinyl Alcohol/chemistry ; Hydrophobic and Hydrophilic Interactions ; }, abstract = {Natural plant leaves with multiple functions, for example, spectral features, transpiration, photosynthesis, etc., have played a significant role in the ecosystem, and artificial synthesis of plant leaves with multiple functions of natural ones is still a great challenge. Herein, this work presents an aerogel-involved living leaf (AL), most similar to natural ones so far, by embedding super-hydrophobic SiO2 aerogel microparticles in polyvinyl alcohol hydrogel in the presence of hygroscopic salt and chlorophyllin copper sodium to form solid-liquid-vapor triple-state gel. The AL shows a high spectral similarity with all sampled 15 species of natural leaves and exhibits ≈4-7 times transpiration speed higher than natural leaves. More importantly, AL can achieve several times higher photosynthesis than natural leaves without the energy provided by the respiratory action of natural ones. This work demonstrates the feasibility of creating ALs with natural leaf-like triple-state gel structures and multiple functions, opening up new avenues for energy conversion, environmental engineering, and biomimetic applications.}, } @article {pmid38847056, year = {2024}, author = {Michelotti, G and Egger-Sigg, M and Bornstein, MM}, title = {[Komplexes Odontom im Unterkieferfrontzahnbereich bei einer 16-jährigen Patientin - Diagnostik, Therapie und Nachsorge].}, journal = {Swiss dental journal}, volume = {134}, number = {3}, pages = {}, doi = {10.61872/sdj-2024-03-08}, pmid = {38847056}, issn = {2296-6498}, mesh = {Adolescent ; Humans ; Diagnosis, Differential ; Mandibular Neoplasms/surgery/pathology/diagnosis ; Maxillary Neoplasms/surgery/pathology/diagnosis ; *Odontoma/surgery/diagnosis/pathology ; }, abstract = {Odontome gelten zusammen mit den Amelo- blastomen als die häufigsten odontogenen Tumoren. Sie entstehen während der embryo- nalen Zahnkeimentwicklung durch fehlerhaft differenziertes Keimgewebe und werden daher auch als Hamartome bezeichnet. Somit sind sie also strenggenommen keine klassischen Neoplasien.}, } @article {pmid38846716, year = {2024}, author = {Bradford, D and Rodgers, KE}, title = {Advancements and challenges in amyotrophic lateral sclerosis.}, journal = {Frontiers in neuroscience}, volume = {18}, number = {}, pages = {1401706}, pmid = {38846716}, issn = {1662-4548}, abstract = {Amyotrophic lateral sclerosis (ALS) continues to pose a significant challenge due to the disease complexity and heterogeneous manifestations. Despite recent drug approvals, there remains a critical need for the development of more effective therapies. This review explores the underlying mechanisms involved; including neuroinflammation, glutamate mediated excitotoxicity, mitochondrial dysfunction, and hypermetabolism, and how researchers are trying to develop novel drugs to target these pathways. While progress has been made, the unmet need of ALS patients highlights the urgency for continued research and resource allocation in the pursuit of effective treatments.}, } @article {pmid38846532, year = {2024}, author = {Murage, B and Tan, H and Mashimo, T and Jackson, M and Skehel, PA}, title = {Spinal cord neurone loss and foot placement changes in a rat knock-in model of amyotrophic lateral sclerosis Type 8.}, journal = {Brain communications}, volume = {6}, number = {3}, pages = {fcae184}, pmid = {38846532}, issn = {2632-1297}, abstract = {Amyotrophic lateral sclerosis is an age-dependent cell type-selective degenerative disease. Genetic studies indicate that amyotrophic lateral sclerosis is part of a spectrum of disorders, ranging from spinal muscular atrophy to frontotemporal dementia that share common pathological mechanisms. Amyotrophic lateral sclerosis Type 8 is a familial disease caused by mis-sense mutations in VAPB. VAPB is localized to the cytoplasmic surface of the endoplasmic reticulum, where it serves as a docking point for cytoplasmic proteins and mediates inter-organelle interactions with the endoplasmic reticulum membrane. A gene knock-in model of amyotrophic lateral sclerosis Type 8 based on the VapB[P56S] mutation and VapB gene deletion has been generated in rats. These animals display a range of age-dependent phenotypes distinct from those previously reported in mouse models of amyotrophic lateral sclerosis Type 8. A loss of motor neurones in VapB[P56S/+] and VapB[P56S/P56S] animals is indicated by a reduction in the number of large choline acetyl transferase-staining cells in the spinal cord. VapB[-/-] animals exhibit a relative increase in cytoplasmic TDP-43 levels compared with the nucleus, but no large protein aggregates. Concomitant with these spinal cord pathologies VapB[P56S/+] , VapB[P56S/P56S] and VapB[-/-] animals exhibit age-dependent changes in paw placement and exerted pressures when traversing a CatWalk apparatus, consistent with a somatosensory dysfunction. Extramotor dysfunction is reported in half the cases of motor neurone disease, and this is the first indication of an associated sensory dysfunction in a rodent model of amyotrophic lateral sclerosis. Different rodent models may offer complementary experimental platforms with which to understand the human disease.}, } @article {pmid38845371, year = {2024}, author = {Rooney, J and Murray, D and Meldrum, D and Al-Chalabi, A and Bunte, T and Chiwera, T and Choudhury, M and Chio, A and Fenton, L and Fortune, J and Maidment, L and Manera, U and McDermott, CJ and Meyjes, M and Tattersall, R and Torrieri, MC and Van Damme, P and Vanderlinden, E and Wood, C and van den Berg, LH and Hardiman, O}, title = {REVEALS-a longitudinal cohort study of multifaceted respiratory assessment in ALS.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {25}, number = {7-8}, pages = {661-671}, pmid = {38845371}, issn = {2167-9223}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology/diagnosis/complications ; Male ; Female ; Middle Aged ; Aged ; Longitudinal Studies ; *Disease Progression ; Respiratory Function Tests/methods ; Vital Capacity/physiology ; Cohort Studies ; Cough/physiopathology/diagnosis ; }, abstract = {OBJECTIVE: To systematically assess decline in respiratory measures in amyotrophic lateral sclerosis (ALS) and to examine the impact of sex, disease onset type and baseline morbidity on progression.

METHODS: The REVEALS study (Registry of Endpoints and Validated Experiences in ALS) was conducted between April 2018 and February 2021 in six European ALS centers. Slow and forced vital capacity (S/FVC), sniff nasal inspiratory pressure (SNIP), peak cough flow, amyotrophic lateral sclerosis functional rating scale-revised (ALSFRS-R), and respiratory morbidity were collected. Data were analyzed using a Bayesian multiple outcomes random effects model.

RESULTS: Two hundred and eighty participants had a median of three assessments (IQR 2.0, 5.0) over a median of 8 months (IQR 2.3, 14.1). There were 974 data collection timepoints. Differences in respiratory measures and rates of decline between disease-onset and sex subgroups were identified. Females had lower scores in all respiratory measures and females with bulbar onset ALS had faster decline compared with other sub-groups. These differences were not detected by the ALSFRS-r respiratory subscale. Dyspnea, orthopnea, and a higher King's stage at baseline were associated with lower respiratory scores throughout follow-up, while having a regular productive cough at baseline was associated with lower peak cough flow scores.

CONCLUSION: Respiratory function declines more quickly in females with ALS compared with males when measured by FVC, SVC, SNIP, or PCF, but not the ALSFRS-R respiratory sub-score. Higher baseline King's staging and the presence of clinical respiratory symptoms at baseline were associated with worse respiratory function. The ALSFRS-R respiratory sub-score is poorly correlated with objective respiratory measurements.}, } @article {pmid38845026, year = {2024}, author = {Kettunen, P and Koistinaho, J and Rolova, T}, title = {Contribution of CNS and extra-CNS infections to neurodegeneration: a narrative review.}, journal = {Journal of neuroinflammation}, volume = {21}, number = {1}, pages = {152}, pmid = {38845026}, issn = {1742-2094}, support = {334525//Research Council of Finland/ ; }, mesh = {Humans ; *Neurodegenerative Diseases/pathology ; *Central Nervous System Infections ; Animals ; }, abstract = {Central nervous system infections have been suggested as a possible cause for neurodegenerative diseases, particularly sporadic cases. They trigger neuroinflammation which is considered integrally involved in neurodegenerative processes. In this review, we will look at data linking a variety of viral, bacterial, fungal, and protozoan infections to Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis and unspecified dementia. This narrative review aims to bring together a broad range of data currently supporting the involvement of central nervous system infections in the development of neurodegenerative diseases. The idea that no single pathogen or pathogen group is responsible for neurodegenerative diseases will be discussed. Instead, we suggest that a wide range of susceptibility factors may make individuals differentially vulnerable to different infectious pathogens and subsequent pathologies.}, } @article {pmid38844617, year = {2024}, author = {Tyr, A and Heldring, N and Zilg, B}, title = {Examining the use of alternative light sources in medico-legal assessments of blunt-force trauma: a systematic review.}, journal = {International journal of legal medicine}, volume = {138}, number = {5}, pages = {1925-1938}, pmid = {38844617}, issn = {1437-1596}, mesh = {Humans ; *Contusions ; *Wounds, Nonpenetrating ; Light ; Forensic Medicine/methods ; }, abstract = {The ability to analyze blunt-force trauma is crucial for deciphering valuable clues concerning mechanisms of injury and as evidence for medico-legal investigations. The use of alternate light sources (ALS) has been studied over the past decade, and is proposed to outperform conventional white light (CWL) during bruise assessments. In response to the growing interest of the technology worldwide, a systematic review of the literature was conducted according to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) to address the ability of ALS to detect and visualize bruising. From an initial 4055 records identified, ten studies met the eligibly criteria and were selected for this review. Evaluation also included a novel framework, referred to as SPICOT, to further systematically assess both scientific evidence and risk of bias in forensic literature. Analysis reveals that narrowband wavelengths within in the infrared or ultraviolet spectral ranges do not significantly outperform CWL in visualizing or detecting bruising. However, wavelengths within the visible spectrum, particularly 415 nm combined with longpass or bandpass yellow filters, are more effective. However, the majority of selected studies only address the sensitivity of ALS, and therefore, results may only be considered valid when the location of a bruise is known. Further investigation is required to understand the specificity of ALS, in particular how the use of topical cosmetic products, previous wounds/scar-tissue, tattoos, moles and freckles may affect detection. The ethical concern regarding the interpretation of enhanced visualized trauma should also be considered in prospect discussions prior to implementing ALS into routine practice. Nevertheless, this review finds that narrowband ALS within the visible spectrum demonstrates potential for improved injury documentation, outperforming CWL in the detection and visualization of bruising.}, } @article {pmid38844339, year = {2024}, author = {Robinson, G}, title = {Neuropsychological assessment in ALS.}, journal = {Journal of neurology, neurosurgery, and psychiatry}, volume = {95}, number = {8}, pages = {692}, pmid = {38844339}, issn = {1468-330X}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/psychology/diagnosis/complications ; *Neuropsychological Tests ; Cognition Disorders/diagnosis ; }, } @article {pmid38842106, year = {2024}, author = {Neel, DV and Baselga-Garriga, C and Benson, M and Keegan, M and Chase, M and D'Agostino, D and Drake, K and Hagar, JL and Hasenoehrl, MG and Kulesa-Kelley, J and Leite, A and Mohapatra, S and Portaro, SM and Pothier, LM and Rosenthal, J and Sherman, AV and Yu, H and McCaffrey, A and Ho, D and Luppino, S and Bedlack, R and Heitzman, D and Ajroud-Driss, S and Katz, J and Felice, K and Whitaker, C and Ladha, S and Alameda, G and Locatelli, E and Qureshi, IA and Hotchkin, MT and Hayden, MR and Cudkowicz, ME and Babu, S and Berry, JD and Paganoni, S}, title = {Multicenter expanded access program for access to investigational products for amyotrophic lateral sclerosis.}, journal = {Muscle & nerve}, volume = {70}, number = {2}, pages = {232-239}, doi = {10.1002/mus.28169}, pmid = {38842106}, issn = {1097-4598}, support = {T32 GM144273/GM/NIGMS NIH HHS/United States ; //I AM ALS/ ; //Biohaven Pharmaceuticals, Inc/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/drug therapy ; Humans ; United States ; Male ; Female ; Middle Aged ; Aged ; Drugs, Investigational/therapeutic use ; United States Food and Drug Administration ; Adult ; Health Services Accessibility ; Adaptive Clinical Trials as Topic ; }, abstract = {INTRODUCTION/AIMS: Expanded access (EA) is a Food and Drug Administration-regulated pathway to provide access to investigational products (IPs) to individuals with serious diseases who are ineligible for clinical trials. The aim of this report is to share the design and operations of a multicenter, multidrug EA program for amyotrophic lateral sclerosis (ALS) across nine US centers.

METHODS: A central coordination center was established to design and conduct the program. Templated documents and processes were developed to streamline study design, regulatory submissions, and clinical operations across protocols. The program included three protocols and provided access to IPs that were being tested in respective regimens of the HEALEY ALS Platform Trial (verdiperstat, CNM-Au8, and pridopidine). Clinical and safety data were collected in all EA protocols (EAPs). The program cohorts comprised participants who were not eligible for the platform trial, including participants at advanced stages of disease progression and with long disease duration.

RESULTS: A total of 85 participants were screened across the 3 EAPs from July 2021 to September 2022. The screen failure rate was 3.5%. Enrollment for the regimens of the platform trial was completed as planned and results informed the duration of the corresponding EAP. The verdiperstat EAP was concluded in December 2022. Mean duration of participation in the verdiperstat EAP was 5.8 ± 4.1 months. The CNM-Au8 and pridopidine EAPs are ongoing.

DISCUSSION: Multicenter EAPs conducted in parallel to randomized clinical trials for ALS can successfully enroll participants who do not qualify for clinical trials.}, } @article {pmid38841627, year = {2024}, author = {Picher-Martel, V and Babu, S and Amato, AA}, title = {TARDBP Mutations in Facial-Onset Sensory and Motor Neuronopathy.}, journal = {Neurology. Genetics}, volume = {10}, number = {3}, pages = {e200160}, pmid = {38841627}, issn = {2376-7839}, abstract = {OBJECTIVES: Facial-onset sensory and motor neuronopathy (FOSMN) is a rare neuromuscular disorder characterized by progressive facial sensory impairment followed by motor dysfunction in a rostro-caudal distribution. FOSMN is clinically and pathologically associated with amyotrophic lateral sclerosis and frontotemporal dementia (ALS/FTD). In contrast to ALS/FTD, the genetic profile of patients with FOSMN and the role of genetic testing are poorly defined.

METHODS: A 66-year-old woman was evaluated in our neuromuscular clinic for progressive facial pain, dysphagia, and dysarthria. Her diagnostic evaluation included brain and cervical MRI, nerve conduction studies and EMG, and an ALS/FTD next-generation sequencing panel.

RESULTS: The patient was diagnosed with FOSMN, and we identified a N390D variant in transactive response DNA-binding protein (TDP-43/TARDBP). This variant has never been reported in FOSMN but was previously reported in 2 cases of ALS, and a N390S variant was also previously reported in FOSMN. A review of the literature revealed that TARDBP mutations are overrepresented in patients with FOSMN compared with patients with ALS/FTD. By contrast, other common familial forms of ALS, including C9ORF72 or SOD1, are respectively absent or rare in FOSMN.

DISCUSSION: FOSMN is pathologically and genetically associated with TDP-43. Therefore, ALS genetic testing that includes specifically TARDBP should be considered in patients with FOSMN.}, } @article {pmid38840222, year = {2024}, author = {Provasek, VE and Kodavati, M and Kim, B and Mitra, J and Hegde, ML}, title = {TDP43 interacts with MLH1 and MSH6 proteins in a DNA damage-inducible manner.}, journal = {Molecular brain}, volume = {17}, number = {1}, pages = {32}, pmid = {38840222}, issn = {1756-6606}, support = {RF1 NS112719/NS/NINDS NIH HHS/United States ; RF1NS112719/AG/NIA NIH HHS/United States ; }, mesh = {Humans ; *DNA-Binding Proteins/metabolism ; *MutL Protein Homolog 1/metabolism ; *DNA Damage ; *Protein Binding/drug effects ; Cell Line, Tumor ; Amyotrophic Lateral Sclerosis/metabolism/genetics/pathology ; Neurons/metabolism ; Middle Aged ; Male ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that affects the motor neuron. One aspect of the neuropathology involved in ALS includes increased genomic damage and impaired DNA repair capability. The TAR-DNA binding protein 43 (TDP43) has been associated with both sporadic and familial forms of ALS, and is typically observed as cytosolic mislocalization of protein aggregates, termed TDP43 proteinopathy. TDP43 is a ubiquitous RNA/DNA binding protein with functional implications in a wide range of disease processes, including the repair of DNA double-strand breaks (DSBs). While TDP43 is widely known to regulate RNA metabolism, our lab has reported it also functions directly at the protein level to facilitate DNA repair. Here, we show that the TDP43 protein interacts with DNA mismatch repair (MMR) proteins MLH1 and MSH6 in a DNA damage-inducible manner. We utilized differentiated SH-SY5Y neuronal cultures to identify this inducible relationship using complementary approaches of proximity ligation assay (PLA) and co-immunoprecipitation (CoIP) assay. We observed that signals of TDP43 interaction with MLH1 and MSH6 increased significantly following a 2 h treatment of 10 μM methylmethanesulfonate (MMS), a DNA alkylating agent used to induce MMR repair. Likewise, we observed this effect was abolished in cell lines treated with siRNA directed against TDP43. Finally, we demonstrated these protein interactions were significantly increased in lumbar spinal cord samples of ALS-affected patients compared to age-matched controls. These results will inform our future studies to understand the mechanisms and consequences of this TDP43-MMR interaction in the context of ALS-affected neurons.}, } @article {pmid38839275, year = {2024}, author = {Palumbo, F and Iazzolino, B and Callegaro, S and Canosa, A and Manera, U and Vasta, R and Grassano, M and Matteoni, E and Cabras, S and Pellegrino, G and Salamone, P and Peotta, L and Casale, F and Fuda, G and Moglia, C and Chio, A and Calvo, A}, title = {Disentangling the relationship between social cognition, executive functions and behaviour changes in amyotrophic lateral sclerosis.}, journal = {Journal of neurology, neurosurgery, and psychiatry}, volume = {95}, number = {8}, pages = {722-729}, doi = {10.1136/jnnp-2023-332700}, pmid = {38839275}, issn = {1468-330X}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/psychology/complications/physiopathology ; *Executive Function ; Male ; Female ; *Social Cognition ; Middle Aged ; Cross-Sectional Studies ; *Theory of Mind/physiology ; Aged ; Neuropsychological Tests ; Cognitive Dysfunction/psychology/diagnosis ; Case-Control Studies ; }, abstract = {BACKGROUND: Social cognition (SC) deficits are included in the amyotrophic lateral sclerosis-frontotemporal spectrum disorder (ALS-FTDS) revised diagnostic criteria. However, the impact of SC assessment on cognitive classification and the cognitive-behavioural correlates of SC remain unclear. This cross-sectional study aimed to assess the impact of SC assessment on ALS-FTDS categorisation and explore the relationship of SC with executive functions (EF) and behaviour changes in a cohort of ALS patients.

METHODS: 121 patients and 56 healthy controls from the Turin ALS Centre underwent cognitive/behavioural testing, including the SC subdomains of facial emotion recognition, and cognitive and affective theory of mind (ToM).

RESULTS: Patients performed significantly worse than controls in all SC explored domains, and 45% of patients exhibited a deficit in at least one SC test, dissociated from the presence of EF deficits. In 13% of cases, the SC deficit was isolated and subclinical. SC assessment contributed to the attribution of cognitive impairment in 10% of patients. Through a statistical clustering approach, we found that ToM only partially overlaps with EF while behaviour changes are associated with emotional disorders (anxiety and depression).

CONCLUSIONS: SC is overall independent of EF in ALS, with ToM only partially associated with specific EF measures, and behaviour changes associated with emotional disorders. The influence of SC on cognitive categorisation and the frequent identification of a subclinical SC impairment have implications in a clinical setting, considering the substantial impact of cognitive impairment on disease burden and therapeutic choices.}, } @article {pmid38838600, year = {2024}, author = {Ou, H and Zhang, P and Wang, X and Lin, M and Li, Y and Wang, G}, title = {Gaining insights into the responses of individual yeast cells to ethanol fermentation using Raman tweezers and chemometrics.}, journal = {Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy}, volume = {319}, number = {}, pages = {124584}, doi = {10.1016/j.saa.2024.124584}, pmid = {38838600}, issn = {1873-3557}, mesh = {*Spectrum Analysis, Raman/methods ; *Ethanol/metabolism ; *Saccharomyces cerevisiae/metabolism ; *Fermentation ; *Principal Component Analysis ; Least-Squares Analysis ; Optical Tweezers ; Single-Cell Analysis/methods ; }, abstract = {Saccharomyces cerevisiae is the most common microbe used for the industrial production of bioethanol, and it encounters various stresses that inhibit cell growth and metabolism during fermentation. However, little is currently known about the physiological changes that occur in individual yeast cells during ethanol fermentation. Therefore, in this work, Raman spectroscopy and chemometric techniques were employed to monitor the metabolic changes of individual yeast cells at distinct stages during high gravity ethanol fermentation. Raman tweezers was used to acquire the Raman spectra of individual yeast cells. Multivariate curve resolution-alternating least squares (MCR-ALS) and principal component analysis were employed to analyze the Raman spectra dataset. MCR-ALS extracted the spectra of proteins, phospholipids, and triacylglycerols and their relative contents in individual cells. Changes in intracellular biomolecules showed that yeast cells undergo three distinct physiological stages during fermentation. In addition, heterogeneity among yeast cells significantly increased in the late fermentation period, and different yeast cells may respond to ethanol stress via different mechanisms. Our findings suggest that the combination of Raman tweezers and chemometrics approaches allows for characterizing the dynamics of molecular components within individual cells. This approach can serve as a valuable tool in investigating the resistance mechanism and metabolic heterogeneity of yeast cells during ethanol fermentation.}, } @article {pmid38838248, year = {2024}, author = {Liss, J and Berisha, V}, title = {Operationalizing Clinical Speech Analytics: Moving From Features to Measures for Real-World Clinical Impact.}, journal = {Journal of speech, language, and hearing research : JSLHR}, volume = {67}, number = {11}, pages = {4226-4232}, doi = {10.1044/2024_JSLHR-24-00039}, pmid = {38838248}, issn = {1558-9102}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis ; *Speech Production Measurement/methods ; Speech ; Reproducibility of Results ; }, abstract = {OBJECTIVE: This research note advocates for a methodological shift in clinical speech analytics, emphasizing the transition from high-dimensional speech feature representations to clinically validated speech measures designed to operationalize clinically relevant constructs of interest. The aim is to enhance model generalizability and clinical applicability in real-world settings.

METHOD: We outline the challenges of using conventional supervised machine learning models in clinical speech analytics, particularly their limited generalizability and interpretability. We propose a new framework focusing on speech measures that are closely tied to specific speech constructs and have undergone rigorous validation. This research note discusses a case study involving the development of a measure for articulatory precision in amyotrophic lateral sclerosis (ALS), detailing the process from ideation through Food and Drug Administration (FDA) breakthrough status designation.

RESULTS: The case study demonstrates how the operationalization of the articulatory precision construct into a quantifiable measure yields robust, clinically meaningful results. The measure's validation followed the V3 framework (verification, analytical validation, and clinical validation), showing high correlation with clinical status and speech intelligibility. The practical application of these measures is exemplified in a clinical trial and designation by the FDA as a breakthrough status device, underscoring their real-world impact.

CONCLUSIONS: Transitioning from speech features to speech measures offers a more targeted approach for developing speech analytics tools in clinical settings. This shift ensures that models are not only technically sound but also clinically relevant and interpretable, thereby bridging the gap between laboratory research and practical health care applications. We encourage further exploration and adoption of this approach for developing interpretable speech representations tailored to specific clinical needs.}, } @article {pmid38838021, year = {2024}, author = {Ho, DM and Shaban, M and Mahmood, F and Ganguly, P and Todeschini, L and Van Vactor, D and Artavanis-Tsakonas, S}, title = {cAMP/PKA signaling regulates TDP-43 aggregation and mislocalization.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {121}, number = {24}, pages = {e2400732121}, pmid = {38838021}, issn = {1091-6490}, support = {R21 NS123207/NS/NINDS NIH HHS/United States ; R21NS123207//HHS | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; }, mesh = {Animals ; *Cyclic AMP/metabolism ; *Drosophila melanogaster/metabolism ; *Cyclic AMP-Dependent Protein Kinases/metabolism/genetics ; *Drosophila Proteins/metabolism/genetics ; *Signal Transduction ; *DNA-Binding Proteins/metabolism/genetics ; Amyotrophic Lateral Sclerosis/metabolism/genetics ; Humans ; Motor Neurons/metabolism ; }, abstract = {Cytoplasmic mislocalization and aggregation of TDP-43 protein are hallmarks of amyotrophic lateral sclerosis (ALS) and are observed in the vast majority of both familial and sporadic cases. How these two interconnected processes are regulated on a molecular level, however, remains enigmatic. Genome-wide screens for modifiers of the ALS-associated genes TDP-43 and FUS have identified the phospholipase D (Pld) pathway as a key regulator of ALS-related phenotypes in the fruit fly Drosophila melanogaster [M. W. Kankel et al., Genetics 215, 747-766 (2020)]. Here, we report the results of our search for downstream targets of the enzymatic product of Pld, phosphatidic acid. We identify two conserved negative regulators of the cAMP/PKA signaling pathway, the phosphodiesterase dunce and the inhibitory subunit PKA-R2, as modifiers of pathogenic phenotypes resulting from overexpression of the Drosophila TDP-43 ortholog TBPH. We show that knockdown of either of these genes results in a mitigation of both TBPH aggregation and mislocalization in larval motor neuron cell bodies, as well as an amelioration of adult-onset motor defects and shortened lifespan induced by TBPH. We determine that PKA kinase activity is downstream of both TBPH and Pld and that overexpression of the PKA target CrebA can rescue TBPH mislocalization. These findings suggest a model whereby increasing cAMP/PKA signaling can ameliorate the molecular and functional effects of pathological TDP-43.}, } @article {pmid38837845, year = {2024}, author = {Huang, Q and Zhang, Q and Cao, B}, title = {Causal relationship between PCSK9 inhibitor and common neurodegenerative diseases: A drug target Mendelian randomization study.}, journal = {Brain and behavior}, volume = {14}, number = {6}, pages = {e3543}, pmid = {38837845}, issn = {2162-3279}, support = {2022NSFSC0749 to BC//the National Natural Science Fund of Sichuan/ ; }, mesh = {Humans ; Alzheimer Disease/genetics/drug therapy ; Amyotrophic Lateral Sclerosis/genetics/drug therapy/epidemiology ; Genome-Wide Association Study ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology/adverse effects ; *Mendelian Randomization Analysis ; *Neurodegenerative Diseases/drug therapy/genetics ; Parkinson Disease/genetics/drug therapy ; *PCSK9 Inhibitors ; *Polymorphism, Single Nucleotide ; Proprotein Convertase 9 ; }, abstract = {BACKGROUND: In addition to lowering cholesterol levels, the proprotein convertase subtilis kexin 9 (PCSK9) inhibitor has a variety of effects, including anti-neuroapoptosis. However, the effects of PCSK9 inhibitors on neurodegenerative diseases are controversial. Therefore, we used drug-targeted Mendelian randomization (MR) analysis to investigate the effects of PCSK9 inhibitors on different neurodegenerative diseases.

METHODS: We collected single nucleotide polymorphisms (SNPs) of PCSK9 from published statistics of genome-wide association studies and performed drug target MR analyses to detect a causal relationship between PCSK9 inhibitors and the risk of neurodegenerative diseases. We utilized the effects of 3-Hydroxy -3- methylglutaryl-assisted enzyme A reductase (HMGCR) inhibitors (statin targets) for comparison with PCSK9 inhibitors. Coronary heart disease risk was used as a positive control, and primary outcomes included amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), and Alzheimer's disease (AD).

RESULTS: PCSK9 inhibitors marginally reduced the risk of ALS (OR [95%] = 0.89 [0.77 to 1.00], p = 0.048), while they increased the risk of PD (OR [95%] = 1.417 [1.178 to 1.657], p = 0.004). However, HMGCR inhibitors increased the risk of PD (OR [95%] = 1.907 [1.502 to 2.312], p = 0.001).

CONCLUSION: PCSK9 inhibitors significantly reduce the risk of ALS but increase the risk of PD. HMGCR inhibitors may be the risk factor for PD.}, } @article {pmid38837773, year = {2024}, author = {Connaghan, KP and Green, JR and Eshghi, M and Haenssler, AE and Scheier, ZA and Clark, A and Iyer, A and Richburg, BD and Rowe, HP and Okada, J and Johnson, SA and Onnela, JP and Burke, KM and Berry, JD}, title = {The relationship of rate and pause features to the communicative participation of people living with ALS.}, journal = {Muscle & nerve}, volume = {70}, number = {2}, pages = {217-225}, pmid = {38837773}, issn = {1097-4598}, support = {K23 DC019179/DC/NIDCD NIH HHS/United States ; DP2-MH103909/NH/NIH HHS/United States ; R15 DC018944/DC/NIDCD NIH HHS/United States ; 1R15DC018944/NH/NIH HHS/United States ; NIH-NIDCD K24DC016312/NH/NIH HHS/United States ; K23DC019179/NH/NIH HHS/United States ; DP2 MH103909/MH/NIMH NIH HHS/United States ; K24 DC016312/DC/NIDCD NIH HHS/United States ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology/psychology ; Female ; Male ; Middle Aged ; Aged ; Speech/physiology ; Adult ; Communication ; Self Report ; }, abstract = {INTRODUCTION/AIMS: Many people living with amyotrophic lateral sclerosis (PALS) report restrictions in their day-to-day communication (communicative participation). However, little is known about which speech features contribute to these restrictions. This study evaluated the effects of common speech symptoms in PALS (reduced overall speaking rate, slowed articulation rate, and increased pausing) on communicative participation restrictions.

METHODS: Participants completed surveys (the Communicative Participation Item Bank-short form; the self-entry version of the ALS Functional Rating Scale-Revised) and recorded themselves reading the Bamboo Passage aloud using a smartphone app. Rate and pause measures were extracted from the recordings. The association of various demographic, clinical, self-reported, and acoustic speech features with communicative participation was evaluated with bivariate correlations. The contribution of salient rate and pause measures to communicative participation was assessed using multiple linear regression.

RESULTS: Fifty seven people living with ALS participated in the study (mean age = 61.1 years). Acoustic and self-report measures of speech and bulbar function were moderately to highly associated with communicative participation (Spearman rho coefficients ranged from rs = 0.48 to rs = 0.77). A regression model including participant age, sex, articulation rate, and percent pause time accounted for 57% of the variance of communicative participation ratings.

DISCUSSION: Even though PALS with slowed articulation rate and increased pausing may convey their message clearly, these speech features predict communicative participation restrictions. The identification of quantitative speech features, such as articulation rate and percent pause time, is critical to facilitating early and targeted intervention and for monitoring bulbar decline in ALS.}, } @article {pmid38837229, year = {2024}, author = {Ó Murchú, SC and O'Halloran, KD}, title = {BREATHE DMD: boosting respiratory efficacy after therapeutic hypoxic episodes in Duchenne muscular dystrophy.}, journal = {The Journal of physiology}, volume = {602}, number = {14}, pages = {3255-3272}, doi = {10.1113/JP280280}, pmid = {38837229}, issn = {1469-7793}, support = {SFI FFP/19/6628 INSPIRE DMD/SFI_/Science Foundation Ireland/Ireland ; }, mesh = {*Muscular Dystrophy, Duchenne/physiopathology/therapy ; Humans ; *Hypoxia/physiopathology ; Animals ; Respiration ; }, abstract = {Duchenne muscular dystrophy (DMD) is a fatal genetic neuromuscular disorder, characterised by progressive decline in skeletal muscle function due to the secondary consequences of dystrophin deficiency. Weakness extends to the respiratory musculature, and cardiorespiratory failure is the leading cause of death in men with DMD. Intermittent hypoxia has emerged as a potential therapy to counteract ventilatory insufficiency by eliciting long-term facilitation of breathing. Mechanisms of sensory and motor facilitation of breathing have been well delineated in animal models. Various paradigms of intermittent hypoxia have been designed and implemented in human trials culminating in clinical trials in people with spinal cord injury and amyotrophic lateral sclerosis. Application of therapeutic intermittent hypoxia to DMD is considered together with discussion of the potential barriers to progression owing to the complexity of this devastating disease. Notwithstanding the considerable challenges and potential pitfalls of intermittent hypoxia-based therapies for DMD, we suggest it is incumbent on the research community to explore the potential benefits in pre-clinical models. Intermittent hypoxia paradigms should be implemented to explore the proclivity to express respiratory plasticity with the longer-term aim of preserving and potentiating ventilation in pre-clinical models and people with DMD.}, } @article {pmid38836336, year = {2024}, author = {Foucher, J and Öijerstedt, L and Lovik, A and Sun, J and Ismail, MA and Sennfält, S and Savitcheva, I and Estenberg, U and Pagani, M and Fang, F and Pereira, JB and Ingre, C}, title = {ECAS correlation with metabolic alterations on FDG-PET imaging in ALS.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {25}, number = {7-8}, pages = {708-716}, doi = {10.1080/21678421.2024.2361695}, pmid = {38836336}, issn = {2167-9223}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnostic imaging/metabolism ; Male ; Female ; *Fluorodeoxyglucose F18 ; Middle Aged ; *Positron-Emission Tomography/methods ; Aged ; Brain/metabolism/diagnostic imaging ; Cognitive Dysfunction/metabolism/diagnostic imaging ; Adult ; Neuropsychological Tests ; Glucose/metabolism ; Radiopharmaceuticals ; }, abstract = {Background: Cognitive impairment is observed in up to 50% of patients with amyotrophic lateral sclerosis (ALS). The Edinburgh Cognitive and Behavioral ALS Screen (ECAS) is an ALS-specific multi-domain screening tool. Few studies have examined the relationship between ECAS scores and [[18]F]fluorodeoxyglucose positron emission tomography ([[18]F]FDG-PET) findings. Objective: To assess the relationship between ECAS scores and glucose metabolism patterns on [[18]F]FDG -PET images in ALS. Methods: We collected [[18]F]FDG-PET images from 65 patients with ALS and 39 healthy controls. ECAS scores were collected on all patients and we calculated the correlation to [[18]F]FDG-PET in order to investigate the potential links between cognition and glucose metabolism. Results: We observed hypometabolism in the frontal cortex, insula, and limbic system, together with hypermetabolism in the cerebellum in patients with ALS compared to controls. A lower ECAS total score was associated with lower glucose metabolism in the right orbitofrontal gyrus and higher glucose metabolism in lateral occipital, medial occipital, and cerebellar regions, among patients with ALS. Similar results, although less widespread, were observed in the analyses of ECAS ALS-specific scores. Conclusions: The metabolic patterns in [[18]F]FDG -PET show that changes in the glucose metabolism of corresponding areas are related to cognitive dysfunction in ALS, and can be detected using the ECAS.}, } @article {pmid38836001, year = {2024}, author = {Rong, P and Heidrick, L and Pattee, GL}, title = {A multimodal approach to automated hierarchical assessment of bulbar involvement in amyotrophic lateral sclerosis.}, journal = {Frontiers in neurology}, volume = {15}, number = {}, pages = {1396002}, pmid = {38836001}, issn = {1664-2295}, abstract = {INTRODUCTION: As a hallmark feature of amyotrophic lateral sclerosis (ALS), bulbar involvement leads to progressive declines of speech and swallowing functions, significantly impacting social, emotional, and physical health, and quality of life. Standard clinical tools for bulbar assessment focus primarily on clinical symptoms and functional outcomes. However, ALS is known to have a long, clinically silent prodromal stage characterized by complex subclinical changes at various levels of the bulbar motor system. These changes accumulate over time and eventually culminate in clinical symptoms and functional declines. Detection of these subclinical changes is critical, both for mechanistic understanding of bulbar neuromuscular pathology and for optimal clinical management of bulbar dysfunction in ALS. To this end, we developed a novel multimodal measurement tool based on two clinically readily available, noninvasive instruments-facial surface electromyography (sEMG) and acoustic techniques-to hierarchically assess seven constructs of bulbar/speech motor control at the neuromuscular and acoustic levels. These constructs, including prosody, pause, functional connectivity, amplitude, rhythm, complexity, and regularity, are both mechanically and clinically relevant to bulbar involvement.

METHODS: Using a custom-developed, fully automated data analytic algorithm, a variety of features were extracted from the sEMG and acoustic recordings of a speech task performed by 13 individuals with ALS and 10 neurologically healthy controls. These features were then factorized into 10 composite outcome measures using confirmatory factor analysis. Statistical and machine learning techniques were applied to these composite outcome measures to evaluate their reliability (internal consistency), validity (concurrent and construct), and efficacy for early detection and progress monitoring of bulbar involvement in ALS.

RESULTS: The composite outcome measures were demonstrated to (1) be internally consistent and structurally valid in measuring the targeted constructs; (2) hold concurrent validity with the existing clinical and functional criteria for bulbar assessment; and (3) outperform the outcome measures obtained from each constituent modality in differentiating individuals with ALS from healthy controls. Moreover, the composite outcome measures combined demonstrated high efficacy for detecting subclinical changes in the targeted constructs, both during the prodromal stage and during the transition from prodromal to symptomatic stages.

DISCUSSION: The findings provided compelling initial evidence for the utility of the multimodal measurement tool for improving early detection and progress monitoring of bulbar involvement in ALS, which have important implications in facilitating timely access to and delivery of optimal clinical care of bulbar dysfunction.}, } @article {pmid38835240, year = {2024}, author = {McAlary, L and Nan, JR and Shyu, C and Sher, M and Plotkin, SS and Cashman, NR}, title = {Amyloidogenic regions in beta-strands II and III modulate the aggregation and toxicity of SOD1 in living cells.}, journal = {Open biology}, volume = {14}, number = {6}, pages = {230418}, pmid = {38835240}, issn = {2046-2441}, support = {//R. Howard Webster Foundation/ ; //CIHR/ ; //Canadian Consortium for Neurodegeneration/ ; //Brain Canada/ ; }, mesh = {*Superoxide Dismutase-1/metabolism/genetics/chemistry ; Humans ; *Amyotrophic Lateral Sclerosis/metabolism/genetics/pathology ; *Protein Aggregates ; Protein Aggregation, Pathological/genetics/metabolism ; Mutation ; Protein Conformation, beta-Strand ; Models, Molecular ; Proline/metabolism ; Amyloid/metabolism/chemistry ; Protein Folding ; }, abstract = {Mutations in the protein superoxide dismutase-1 (SOD1) promote its misfolding and aggregation, ultimately causing familial forms of the debilitating neurodegenerative disease amyotrophic lateral sclerosis (ALS). Currently, over 220 (mostly missense) ALS-causing mutations in the SOD1 protein have been identified, indicating that common structural features are responsible for aggregation and toxicity. Using in silico tools, we predicted amyloidogenic regions in the ALS-associated SOD1-G85R mutant, finding seven regions throughout the structure. Introduction of proline residues into β-strands II (I18P) or III (I35P) reduced the aggregation propensity and toxicity of SOD1-G85R in cells, significantly more so than proline mutations in other amyloidogenic regions. The I18P and I35P mutations also reduced the capability of SOD1-G85R to template onto previously formed non-proline mutant SOD1 aggregates as measured by fluorescence recovery after photobleaching. Finally, we found that, while the I18P and I35P mutants are less structurally stable than SOD1-G85R, the proline mutants are less aggregation-prone during proteasome inhibition, and less toxic to cells overall. Our research highlights the importance of a previously underappreciated SOD1 amyloidogenic region in β-strand II ([15]QGIINF[20]) to the aggregation and toxicity of SOD1 in ALS mutants, and suggests that β-strands II and III may be good targets for the development of SOD1-associated ALS therapies.}, } @article {pmid38835201, year = {2024}, author = {Tsai, CC and Tao, B and Wong, M and Suntharalingam, H and Abrahao, A and Barnett-Tapia, C}, title = {Sex, racial, and ethnic disparities in motor neuron disease: clinical trial enrolment.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {25}, number = {7-8}, pages = {694-701}, doi = {10.1080/21678421.2024.2358793}, pmid = {38835201}, issn = {2167-9223}, mesh = {Female ; Humans ; Male ; Clinical Trials as Topic ; Ethnicity ; *Healthcare Disparities/ethnology/statistics & numerical data ; *Motor Neuron Disease/ethnology ; Sex Factors ; Racial Groups ; *Patient Selection ; }, abstract = {OBJECTIVE: Motor neuron disease (MND) is a group of neurological diseases, the majority being amyotrophic lateral sclerosis (ALS), with varying clinical presentations across demographics. Clinical trial enrollment reflecting global disease burden improves understanding of diverse presentations and aids personalized therapy development. We assessed the sex, racial, and ethnic composition of MND/ALS clinical trial participants relative to global disease burdens.

METHODS: We searched 'motor neuron disease OR amyotrophic lateral sclerosis' on ClinicalTrials.gov from 02/2000-04/2024. We extracted trial (start year, study site, sponsor location, phase, masking, intervention) and demographic data (sex, race, ethnicity) from randomized interventional studies. We obtained sex-based MND/ALS disease burden estimates from the Global Burden of Disease database. For females, we calculated pooled participation-to-prevalence ratio (PPR) with 95% confidence intervals (CIs), with PPR of 0.8-1.2 indicating adequate enrollment. We used Kruskal-Wallis tests to compare demographic groups across trial characteristics.

RESULTS: Of 85 trials, females comprised 37.47% (n = 5011) of 13,372 participants; the pooled female PPR was 0.97 (95% CI: 0.77-1.16). Of 41 trials (9340 participants) reporting race, 121 (1.30%) participants were Black or African American, 16 (0.17%) American Indian or Alaskan Native, and 6 (0.06%) Native Hawaiian or Other Pacific Islander. 24 trials (595 participants) reported ethnicity, with a minority of Hispanic participants (n = 153; 2.57%).

CONCLUSIONS: MND/ALS clinical trials had adequate female enrollment relative to global disease burdens. Race and ethnicity data were underreported. However, there were enrollment disparities of racial and ethnic groups. Increased trial leadership diversity, equitable enrollment policies, and addressing barriers to participation could improve enrollment diversity.}, } @article {pmid38835198, year = {2024}, author = {Trudel, P and Quesnel-Olivo, MH and Blais, M and Shoesmith, C and Dupré, N}, title = {ALS, MAiD and Tissue Donation: Case Reports from Six Patients' Care Journeys.}, journal = {The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques}, volume = {}, number = {}, pages = {1-2}, doi = {10.1017/cjn.2024.277}, pmid = {38835198}, issn = {0317-1671}, } @article {pmid38834164, year = {2024}, author = {Griñán-Ferré, C and Bellver-Sanchis, A and Guerrero, A and Pallàs, M}, title = {Advancing personalized medicine in neurodegenerative diseases: The role of epigenetics and pharmacoepigenomics in pharmacotherapy.}, journal = {Pharmacological research}, volume = {205}, number = {}, pages = {107247}, doi = {10.1016/j.phrs.2024.107247}, pmid = {38834164}, issn = {1096-1186}, mesh = {Humans ; *Precision Medicine/methods ; *Neurodegenerative Diseases/drug therapy/genetics ; *Pharmacogenetics/methods ; *Epigenesis, Genetic/drug effects ; Animals ; Epigenomics/methods ; }, abstract = {About 80 % of brain disorders have a genetic basis. The pathogenesis of most neurodegenerative diseases is associated with a myriad of genetic defects, epigenetic alterations (DNA methylation, histone/chromatin remodeling, miRNA dysregulation), and environmental factors. The emergence of new sequencing technologies and tools to study the epigenome has led to identifying predictive biomarkers for earlier diagnosis, opening up the possibility of prophylactical interventions. As a result, advances in pharmacogenetics and pharmacoepigenomics now allow for personalized treatments based on the profile of each patient and the specific genetic and epigenetic mechanisms involved. This Review highlights the complexity of neurodegenerative diseases and the variability in patient responses to pharmacotherapy, emphasizing the influence of genetic polymorphisms on the pharmacokinetics and pharmacodynamics of drugs used to treat those conditions. We specifically discuss the potential modulatory effect of several genetic polymorphisms associated with an increased risk of developing different neurodegenerative diseases. We explore genetic and genomic technologies and the potential of analyzing individual-specific drug metabolism to predict and influence drug response and associated clinical outcomes. We also provide insights into the mechanism of action of the drugs under investigation and their potential impact on disease-modifying pathways. Finally, the Review underscores the great potential of this field to enhance the effectiveness and safety of drug treatments through personalized medicine.}, } @article {pmid38833116, year = {2024}, author = {Mubeen, H and Masood, A and Zafar, A and Khan, ZQ and Khan, MQ and Nisa, AU}, title = {Insights into AlphaFold's breakthrough in neurodegenerative diseases.}, journal = {Irish journal of medical science}, volume = {193}, number = {5}, pages = {2577-2588}, pmid = {38833116}, issn = {1863-4362}, mesh = {Humans ; *Neurodegenerative Diseases/physiopathology ; Artificial Intelligence ; Deep Learning ; Parkinson Disease ; Alzheimer Disease ; Algorithms ; Frontotemporal Dementia/genetics ; }, abstract = {Neurodegenerative diseases (ND) are disorders of the central nervous system (CNS) characterized by impairment in neurons' functions, and complete loss, leading to memory loss, and difficulty in learning, language, and movement processes. The most common among these NDs are Alzheimer's disease (AD) and Parkinson's disease (PD), although several other disorders also exist. These are frontotemporal dementia (FTD), amyotrophic lateral syndrome (ALS), Huntington's disease (HD), and others; the major pathological hallmark of NDs is the proteinopathies, either of amyloid-β (Aβ), tauopathies, or synucleinopathies. Aggregation of proteins that do not undergo normal configuration, either due to mutations or through some disturbance in cellular pathway contributes to the diseases. Artificial Intelligence (AI) and deep learning (DL) have proven to be successful in the diagnosis and treatment of various congenital diseases. DL approaches like AlphaFold (AF) are a major leap towards success in CNS disorders. This 3D protein geometry modeling algorithm developed by DeepMind has the potential to revolutionize biology. AF has the potential to predict 3D-protein confirmation at an accuracy level comparable to experimentally predicted one, with the additional advantage of precisely estimating protein interactions. This breakthrough will be beneficial to identify diseases' advancement and the disturbance of signaling pathways stimulating impaired functions of proteins. Though AlphaFold has solved a major problem in structural biology, it cannot predict membrane proteins-a beneficial approach for drug designing.}, } @article {pmid38832321, year = {2024}, author = {Patel, JS and McCall, NS and Thomas, M and Zhou, J and Higgins, KA and Bradley, JD and Tian, S and McDonald, MW and Kesarwala, AH and Stokes, WA}, title = {Immune System Dose With Proton Versus Photon Radiotherapy for Treatment of Locally Advanced NSCLC.}, journal = {International journal of particle therapy}, volume = {12}, number = {}, pages = {100016}, pmid = {38832321}, issn = {2331-5180}, abstract = {PURPOSE: Emerging data have illuminated the impact of effective radiation dose to immune cells (EDIC) on outcomes in patients with locally advanced, unresectable non-small cell lung cancer (NSCLC) treated with intensity-modulated radiotherapy (IMRT). Hypothesizing that intensity-modulated proton therapy (IMPT) may reduce EDIC versus IMRT, we conducted a dosimetric analysis of patients treated at our institution.

MATERIALS AND METHODS: Data were retrospectively collected for 12 patients with locally advanced, unresectable NSCLC diagnosed between 2019 and 2021 who had physician-approved IMRT and IMPT plans. Data to calculate EDIC from both Jin et al (PMID: 34944813) and Ladbury et al's (PMID: 31175902) models were abstracted. Paired t tests were utilized to compare the difference in mean EDIC between IMPT and IMRT plans.

RESULTS: IMPT decreased EDIC for 11 of 12 patients (91.7%). The mean EDIC per the Jin model was significantly lower with IMPT than IMRT (3.04 GyE vs 4.99 Gy, P < .001). Similarly, the mean EDIC per the Ladbury model was significantly lower with IMPT than IMRT (4.50 GyE vs 7.60 Gy, P < .002). Modeled 2-year overall survival was significantly longer with IMPT than IMRT (median 71% vs 63%; P = .03).

CONCLUSION: IMPT offers a statistically significant reduction in EDIC compared to IMRT. Given the emergence of EDIC as a modifiable prognostic factor in treatment planning, our dosimetric study highlights a potential role for IMPT to address an unmet need in improving oncologic outcomes in patients with locoregionally advanced NSCLC.}, } @article {pmid38832104, year = {2024}, author = {Oh, HJ and Lee, WJ and Sung, JJ and Hong, YH and , }, title = {Individualized predictions for clinical milestone in amyotrophic lateral sclerosis: A multialgorithmic approach.}, journal = {Digital health}, volume = {10}, number = {}, pages = {20552076241260120}, pmid = {38832104}, issn = {2055-2076}, abstract = {OBJECTIVE: The phenotypic heterogeneity and complex disease trajectory complicate the ability to predict specific clinical milestone for individual patients with amyotrophic lateral sclerosis (ALS). Here we developed individualized prediction models to estimate the time to the loss of autonomy in swallowing function.

METHODS: Utilizing the Pooled Resource Open-Access ALS Clinical Trials (PRO-ACT) database, we built three models of distinct time-to-event prediction algorithms: accelerated failure time (AFT), cox proportional hazard (COX) and random survival forest (RSF) for an individualized risk assessment of the swallowing milestone. The target variable was defined as the time to a decline in the ALSFRS-R swallowing item score to 1 or below, indicating a need for supplementary tube feeding.

RESULTS: Internal cross-validation revealed the median concordance index (C-index) of 0.851 (IQR, 0.842-0.859) for AFT, 0.850 (0.841-0.859) for COX and 0.846 (0.839-0.854) for RSF, and all models demonstrated good distributional calibration with predicted and observed event probabilities closely matched across different time intervals. For external validation with a registry dataset with characteristics different from PRO-ACT, the discriminative power was replicated with comparable C-indices for all models, whereas the calibration revealed a left-skewed distribution suggesting a bias towards overestimation of event probabilities in real-world data. While all models were effective at stratifying patients, the results of RSF model, unlike AFT and COX, did not match well with the KM curves of the corresponding risk groups, supporting the importance of nuanced understanding of data structure and algorithmic properties.

CONCLUSION: Our models are implemented into a web application which could be applied to individualized counselling, management and clinical trial design for gastrostomy intervention. Further studies for model optimization will advance personalized care in patients with ALS.}, } @article {pmid38831349, year = {2024}, author = {López-Carbonero, JI and García-Toledo, I and Fernández-Hernández, L and Bascuñana, P and Gil-Moreno, MJ and Matías-Guiu, JA and Corrochano, S}, title = {In vivo diagnosis of TDP-43 proteinopathies: in search of biomarkers of clinical use.}, journal = {Translational neurodegeneration}, volume = {13}, number = {1}, pages = {29}, pmid = {38831349}, issn = {2047-9158}, support = {2022-5A/BMD-24221//Consejería de Educación, Juventud y Deporte, Comunidad de Madrid/ ; PDI2020-1153-70RB-100/AEI/10.13039/501100011033//Ministerio de Ciencia e Innovación/ ; CM23/00094//Instituto de Salud Carlos III/ ; INT20/00079//Instituto de Salud Carlos III/ ; INT23/00017//Instituto de Salud Carlos III/ ; }, mesh = {Humans ; *TDP-43 Proteinopathies/diagnosis/metabolism/genetics ; *Biomarkers/analysis/metabolism ; *DNA-Binding Proteins/metabolism ; Brain/metabolism/pathology ; }, abstract = {TDP-43 proteinopathies are a heterogeneous group of neurodegenerative disorders that share the presence of aberrant, misfolded and mislocalized deposits of the protein TDP-43, as in the case of amyotrophic lateral sclerosis and some, but not all, pathological variants of frontotemporal dementia. In recent years, many other diseases have been reported to have primary or secondary TDP-43 proteinopathy, such as Alzheimer's disease, Huntington's disease or the recently described limbic-predominant age-related TDP-43 encephalopathy, highlighting the need for new and accurate methods for the early detection of TDP-43 proteinopathy to help on the stratification of patients with overlapping clinical diagnosis. Currently, TDP-43 proteinopathy remains a post-mortem pathologic diagnosis. Although the main aim is to determine the pathologic TDP-43 proteinopathy in the central nervous system (CNS), the ubiquitous expression of TDP-43 in biofluids and cells outside the CNS facilitates the use of other accessible target tissues that might reflect the potential TDP-43 alterations in the brain. In this review, we describe the main developments in the early detection of TDP-43 proteinopathies, and their potential implications on diagnosis and future treatments.}, } @article {pmid38830342, year = {2024}, author = {Li, J and Li, S and Fei, G}, title = {Potential Correlation between Tea Intake and the Risk of Amyotrophic Lateral Sclerosis: A Mendelian Randomization Study.}, journal = {Neuro-degenerative diseases}, volume = {24}, number = {2}, pages = {45-53}, doi = {10.1159/000539590}, pmid = {38830342}, issn = {1660-2862}, mesh = {*Amyotrophic Lateral Sclerosis/genetics/epidemiology ; Humans ; *Tea ; *Mendelian Randomization Analysis/methods ; *Polymorphism, Single Nucleotide/genetics ; Risk Factors ; }, abstract = {INTRODUCTION: There were limited observation studies on the association between tea intake and amyotrophic lateral sclerosis (ALS) with inconsistent results. This study aimed to determine the potential relationship between tea intake and ALS by a two-sample Mendelian randomization (MR) analysis.

METHODS: We identified 41 independent SNPs strongly associated with tea intake from 448,060 participants of European ancestry in the UK Biobank. Summary statistics associated with ALS were also obtained from the UK Biobank including 20,806 cases and 59,804 controls. The study used MR analysis to assess the potential effect of tea consumption on ALS, and several methods such as sensitivity analyses and MR-pleiotropy residual sum and outlier method were performed to further test the robustness of our findings.

RESULTS: The F statistic was more than 10 in each SNP, which meets the first assumption for the MR study. Using the inverse variance weighted MR analysis as the primary method, we found that a one standard deviation increase in tea consumption was associated with a 14% lower risk of ALS (OR = 0.86, 95% CI = 0.74-0.99, p < 0.05). Sensitivity analyses detected no potential pleiotropy and directional heterogeneity.

CONCLUSION: Our MR study supported the potential relationship between tea intake and ALS risk, suggesting the potential advantages of tea intake for preventing ALS. Future clinical trials and research are needed to further validate the results and elucidate possible mechanisms.}, } @article {pmid38830304, year = {2024}, author = {Chin, B and Um, J and Kim, MK and Kim, HS and Yim, HS and Cho, HJ and Lim, SY and Kim, Y and Jeon, J and Park, JS}, title = {Clinical presentation, viral shedding, and neutralizing antibody responses of mpox cases in South Korea: Single center experience.}, journal = {Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology}, volume = {173}, number = {}, pages = {105692}, doi = {10.1016/j.jcv.2024.105692}, pmid = {38830304}, issn = {1873-5967}, mesh = {Humans ; Male ; Female ; Adult ; Republic of Korea/epidemiology ; *Antibodies, Neutralizing/blood ; Middle Aged ; *Virus Shedding ; Young Adult ; *Antibodies, Viral/blood ; Disease Outbreaks ; DNA, Viral/blood ; Mpox, Monkeypox ; }, abstract = {BACKGROUND: A global mpox outbreak occurred in 2022, and a domestic outbreak started in South Korea in April 2023. This study aimed to evaluate the clinical characteristics, viral shedding, and immune response of mpox in South Korea.

METHODS: Patients hospitalized with mpox in the National Medical Center between September 2022 and June 2023 were included in this study. Oropharyngeal (OP), anogenital lesion (AL), and skin lesion (SL) swabs and blood samples were collected, and monkeypox virus (MPXV) DNA using real-time polymerase chain reaction (RT-PCR) and culture assays were performed. Neutralizing antibodies (NAbs) against MPXV A.2.1, B.1.1, and B.1.3 were detected using plaque reduction neutralization tests.

RESULTS: Eighteen patients were enrolled, of whom 17 (94.4 %) were male, with a median (IQR) age of 32.5 (24-51) years. While nine (50 %) were HIV-infected individuals, none of them revealed CD4+ counts less than 200 cells/μL. MPXV DNA was detected in 87.3 % and 82.7 % of patient's ALs and SLs, respectively, until 2 weeks after symptom onset. While MPXV was isolated for up to 15 days in all three sample types, the culture positivity decreased to 53.8 % and 42.9 % in ALs and SLs after 10 days, respectively, and 28.6 % and 22.2 %, respectively, after 2 weeks from symptom onset. The NAb titers against MPXV A.2.1 were significantly lower than those against B.1.1 and B.1.3.

CONCLUSIONS: Infectious MPXV was isolated from various anatomical sites up to 15 days after symptom onset. The MPXV NAb response was varied among different lineages, and this implies limited cross-lineage protection.}, } @article {pmid38830181, year = {2024}, author = {Weemering, DN and Beelen, A and Kliest, T and van Leeuwen, LAG and van den Berg, LH and van Eijk, RPA}, title = {Trial Participation in Neurodegenerative Diseases: Barriers and Facilitators: A Systematic Review and Meta-Analysis.}, journal = {Neurology}, volume = {103}, number = {1}, pages = {e209503}, pmid = {38830181}, issn = {1526-632X}, mesh = {Humans ; *Neurodegenerative Diseases/drug therapy ; *Clinical Trials as Topic ; *Patient Participation ; Patient Selection ; }, abstract = {BACKGROUND AND OBJECTIVES: Clinical trials in neurodegenerative diseases often encounter selective enrollment and under-representation of certain patient populations. This delays drug development and substantially limits the generalizability of clinical trial results. To inform recruitment and retention strategies, and to better understand the generalizability of clinical trial populations, we investigated which factors drive participation.

METHODS: We reviewed the literature systematically to identify barriers to and facilitators of trial participation in 4 major neurodegenerative disease areas: Alzheimer disease, Parkinson disease, amyotrophic lateral sclerosis, and Huntington disease. Inclusion criteria included original research articles published in a peer-reviewed journal and evaluating barriers to and/or facilitators of participation in a clinical trial with a drug therapy (either symptomatic or disease-modifying). The Critical Appraisal Skills Program checklist for qualitative studies was used to assess and ensure the quality of the studies. Qualitative thematic analyses were employed to identify key enablers of trial participation. Subsequently, we pooled quantitative data of each enabler using meta-analytical models.

RESULTS: Overall, we identified 36 studies, enrolling a cumulative sample size of 5,269 patients, caregivers, and health care professionals. In total, the thematic analysis resulted in 31 unique enablers of trial participation; the key factors were patient-related (own health benefit and altruism), study-related (treatment and study burden), and health care professional-related (information availability and patient-physician relationship). When meta-analyzed across studies, responders reported that the reason to participate was mainly driven by (1) the relationship with clinical staff (70% of the respondents; 95% CI 53%-83%), (2) the availability of study information (67%, 95% CI 38%-87%), and (3) the use or absence of a placebo or sham-control arm (53% 95% CI 32%-72%). There was, however, significant heterogeneity between studies (all p < 0.001).

DISCUSSION: We have provided a comprehensive list of reasons why patients participate in clinical trials for neurodegenerative diseases. These results may help to increase participation rates, better inform patients, and facilitate patient-centric approaches, thereby potentially reducing selection mechanisms and improving generalizability of trial results.}, } @article {pmid38829866, year = {2024}, author = {Laurido-Soto, OJ and Faust, IM and Nielsen, SS and Racette, BA}, title = {Adherence to practice parameters in Medicare beneficiaries with amyotrophic lateral sclerosis.}, journal = {PloS one}, volume = {19}, number = {6}, pages = {e0304083}, pmid = {38829866}, issn = {1932-6203}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy ; *Medicare ; Male ; Female ; United States ; Aged ; Retrospective Studies ; Aged, 80 and over ; Guideline Adherence/statistics & numerical data ; Middle Aged ; Practice Patterns, Physicians'/statistics & numerical data ; }, abstract = {OBJECTIVE: Physician adherence to evidence-based clinical practice parameters impacts outcomes of amyotrophic lateral sclerosis (ALS) patients. We sought to investigate compliance with the 2009 practice parameters for treatment of ALS patients in the United States, and sociodemographic and provider characteristics associated with adherence.

METHODS: In this population-based, retrospective cohort study of incident ALS patients in 2009-2014, we included all Medicare beneficiaries age ≥20 with ≥1 International Classification of Diseases, Ninth Revision, Clinical Modification ALS code (335.20) in 2009 and no prior years (N = 8,575). Variables of interest included race/ethnicity, sex, age, urban residence, Area Deprivation Index (ADI), and provider specialty (neurologist vs. non-neurologist). Outcomes were use of practice parameters, which included feeding tubes, non-invasive ventilation (NIV), riluzole, and receiving care from a neurologist.

RESULTS: Overall, 42.9% of patients with ALS received neurologist care. Black beneficiaries (odds ratio [OR] 0.56, 95% confidence interval [CI] 0.47-0.67), older beneficiaries (OR 0.964, 95% CI 0.961-0.968 per year), and those living in disadvantaged areas (OR 0.70, 95% CI 0.61-0.80) received less care from neurologists. Overall, only 26.7% of beneficiaries received a feeding tube, 19.2% NIV, and 15.3% riluzole. Neurologist-treated patients were more likely to receive interventions than other ALS patients: feeding tube (OR 2.80, 95% CI 2.52-3.11); NIV (OR 10.8, 95% CI 9.28-12.6); and riluzole (OR 7.67, 95% CI 6.13-9.58), after adjusting for sociodemographics. These associations remained marked and significant when we excluded ALS patients who subsequently received a code for other diseases that mimic ALS.

CONCLUSIONS: ALS patients treated by neurologists received care consistent with practice parameters more often than those not treated by a neurologist. Black, older, and disadvantaged beneficiaries received less care consistent with the practice parameters.}, } @article {pmid38829511, year = {2025}, author = {Jiang, S and Xu, R}, title = {The Current Potential Pathogenesis of Amyotrophic Lateral Sclerosis.}, journal = {Molecular neurobiology}, volume = {62}, number = {1}, pages = {221-232}, pmid = {38829511}, issn = {1559-1182}, support = {30560042//National Natural Science Foundation of China/ ; 81160161//National Natural Science Foundation of China/ ; 81360198//National Natural Science Foundation of China/ ; 82160255//National Natural Science Foundation of China/ ; GJJ13198//Education Department of Jiangxi Province/ ; GJJ170021//Education Department of Jiangxi Province/ ; 20192BAB205043//Jiangxi Provincial Department of Science and Technology/ ; 20181019//Health and Family Planning Commission of Jiangxi Province/ ; 202210002//Health and Family Planning Commission of Jiangxi Province/ ; 202310119//Health and Family Planning Commission of Jiangxi Province/ ; }, mesh = {Animals ; Humans ; *Amyotrophic Lateral Sclerosis/genetics/microbiology/pathology/physiopathology ; Autophagy/physiology ; Dysbiosis/complications/microbiology/physiopathology ; Extracellular Vesicles/metabolism ; Gastrointestinal Microbiome/physiology ; Mitochondria/metabolism ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease mainly characterized by the accumulation of ubiquitinated proteins in the affected motor neurons. At present, the accurate pathogenesis of ALS remains unclear and there are still no effective treatment measures for ALS. The potential pathogenesis of ALS mainly includes the misfolding of some pathogenic proteins, the genetic variation, mitochondrial dysfunction, autophagy disorders, neuroinflammation, the misregulation of RNA, the altered axonal transport, and gut microbial dysbiosis. Exploring the pathogenesis of ALS is a critical step in searching for the effective therapeutic approaches. The current studies suggested that the genetic variation, gut microbial dysbiosis, the activation of glial cells, and the transportation disorder of extracellular vesicles may play some important roles in the pathogenesis of ALS. This review conducts a systematic review of these current potential promising topics closely related to the pathogenesis of ALS; it aims to provide some new evidences and clues for searching the novel treatment measures of ALS.}, } @article {pmid38829431, year = {2024}, author = {Sabatelli, M and Cerri, F and Zuccarino, R and Patanella, AK and Bernardo, D and Bisogni, G and Tanel, R and Sansone, V and Filosto, M and Lattante, S and Martello, F and Doronzio, PN and Stano, S and Zanfini, BA and Coccia, M and Costantini, EM and Lizio, A and Lucioli, G and Padovani, A and Merlini, GP and Conte, A}, title = {Long-term treatment of SOD1 ALS with tofersen: a multicentre experience in 17 patients.}, journal = {Journal of neurology}, volume = {271}, number = {8}, pages = {5177-5186}, pmid = {38829431}, issn = {1432-1459}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy/blood ; Male ; Female ; Middle Aged ; Aged ; *Superoxide Dismutase-1/genetics ; Neurofilament Proteins/blood/cerebrospinal fluid ; Disease Progression ; Adult ; Retrospective Studies ; Treatment Outcome ; Cohort Studies ; }, abstract = {BACKGROUND: In Amyotrophic Lateral Sclerosis (ALS) patients with SOD1 mutation the intrathecal administration of tofersen slowed down the progression of disease in a controlled clinical study, but results were not statistically significant.

METHODS: In this multicentre, observational study, we evaluated a cohort of 27 ALS-SOD1 patients who were treated with tofersen, focussing on 17 patients who were followed for at least 48 weeks (median period of 84 weeks, range 48-108). We compared the clinical slopes, as measured by ALSFRS-R, MRC scale and Forced Vital Capacity, during tofersen treatment with retrospective data at 1 year prior to therapy. Cerebrospinal fluid (CSF) and serum neurofilament light chains (NFL) were measured in all patients.

RESULTS: Cumulative evaluation of the ALSFRS-R and MRC progression rates showed a statistically significant change during treatment with respect to the period prior to therapy (p = 0.023 and p = 0.007, respectively). The analysis of individual patients showed that nine of the seventeen patients substantially stabilized or slightly improved. Four patients deteriorated during treatment, while in the remaining patients the very slow course did not allow to identify significant changes. CSF and serum NFL concentration markedly decreased in the near totality of patients. Increased levels of white blood cells and proteins in the CSF were found in 60% of patients. Such alterations were clinically asymptomatic in all but two patients who showed an acute pure motor radiculitis, which responded to steroid therapy.

CONCLUSIONS: Clinical findings and NFL analysis strongly suggest that tofersen may have a disease-modifying effect in a subset of SOD1-ALS patients.}, } @article {pmid38829015, year = {2024}, author = {Negri, C and Usberti, N and Contaldo, G and Bracconi, M and Nova, I and Maestri, M and Tronconi, E}, title = {Quantitative Kinetic Insights from Operando-UV/Vis Spectroscopy: An Application to NH3-SCR of NOx on Cu-CHA Catalysts.}, journal = {Angewandte Chemie (International ed. in English)}, volume = {63}, number = {41}, pages = {e202408328}, doi = {10.1002/anie.202408328}, pmid = {38829015}, issn = {1521-3773}, abstract = {We employ UV/Vis Diffuse Reflectance spectroscopy directly coupled with a packed bed flow reactor to extract quantitative kinetic information. We use as a show-case the Cu[II]/Cu[I] redox dynamics during the reduction half cycle of the NH3-Selective Catalytic Reduction (SCR) on Cu-CHA catalysts. Our measurements enable quantification of the fraction of oxidized Cu, reconstructed by Multivariate Curve Resolution (MCR) together with monitoring of the gas-phase evolution during the reaction. These data both on the dynamics of the gas-phase and of the active site oxidation state have been used to assess the reduction half cycle rate equation and estimate the rate constant. Our results in terms of reaction orders and kinetic constant are in line with previous findings in the literature. Overall, our results demonstrate that the combined analysis of the UV spectra and of the gas-phase dynamics provides converging and unparalleled kinetic insight: this approach effectively resolves ambiguities concerning RHC kinetics and mechanism. More in general, this work provides evidence that operando spectroscopy can be used to extract quantitative kinetic information on catalytic cycles.}, } @article {pmid38829007, year = {2024}, author = {Foucher, J and Bunte, TM and Bertone, V and Verschoor, RL and Couillard, M and Straub, C and Genge, A and Ingre, C and van den Berg, LH}, title = {International network for ALS research and care (INARC).}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {25}, number = {7-8}, pages = {795-796}, doi = {10.1080/21678421.2024.2362850}, pmid = {38829007}, issn = {2167-9223}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy ; *Biomedical Research/methods/trends ; }, abstract = {The International Network for Amyotrophic Lateral Sclerosis (ALS) Research and Care (INARC) was founded in 2022. INARC's main goals are to offer a platform dedicated to staff members for ALS clinics and research teams who are not physicians. By nurturing experience and expertise exchanges to improve problem solving skills, the ultimate goal is to increase the standard ALS care and research. This brief report aims to describe the formation of INARC, the 2023 INARC meeting, as well as to report topics discussed, lessons learned and challenges raised by INARC members.}, } @article {pmid38828849, year = {2024}, author = {Mamarabadi, M and Fafoutis, E and Geronimo, A and Walsh, S and Simmons, Z}, title = {Sodium phenylbutyrate-taurursodiol access, adherence and adverse event in patients with amyotrophic lateral sclerosis: Experience at one center in the United States.}, journal = {Muscle & nerve}, volume = {70}, number = {2}, pages = {204-209}, doi = {10.1002/mus.28175}, pmid = {38828849}, issn = {1097-4598}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy/economics ; Male ; Female ; Middle Aged ; Aged ; Adult ; *Medication Adherence ; United States ; Aged, 80 and over ; Phenylbutyrates/therapeutic use/economics ; Health Expenditures ; Retrospective Studies ; }, abstract = {INTRODUCTION/AIMS: Sodium phenylbutyrate-taurursodiol (PB-TURSO) was recently approved for treating amyotrophic lateral sclerosis (ALS). Third-party payors' coverage policies are evolving, and adverse events are just being fully assessed. The goals of this study were to evaluate patients' experiences in obtaining and continuing PB-TURSO and assess adverse events and medication adherence.

METHODS: Medical records of 109 ALS patients who were considered PB-TURSO candidates by the treating physician at a tertiary ALS clinic from October 2022 to May 2023 were reviewed. Data was recorded for demographics, clinical, and insurance information. A survey was e-mailed to patients asking about out-of-pocket expenses for PB-TURSO, financial assistance, medication start and (if applicable) stop dates, and reasons for discontinuation.

RESULTS: Insurance information was available for 91 patients [57 males (62%); mean age 64.8 years (range 25.7-88)]. Of 79 who applied for insurance approval, 71 (90%) were approved; however, 19 required 1-3 appeals. Among 73 patients with available data about medication status, 54 started PB-TURSO and 19 did not, most commonly due to personal choice or out-of-pocket expenses. About 44% of patients (24/54) stopped taking PB-TURSO, primarily due to adverse events. Monthly out-of-pocket expenses varied from $0 to $3500 and 36 patients qualified for financial assistance. Administrative and nursing staff devoted 7.2 hours/week to the insurance authorization process.

DISCUSSION: Most patients received insurance approval for PB-TURSO, but one-fourth required appeals. Some out-of-pocket costs were very high. Investment of staff time was substantial. These findings have implications for insurance coverage of, and adherence to, future ALS treatments.}, } @article {pmid38827490, year = {2024}, author = {Yotsukura, E and Torii, H and Mori, K and Ogawa, M and Hanyuda, A and Negishi, K and Kurihara, T and Tsubota, K}, title = {Slowing of Greater Axial Length Elongation Stemming from the Coronavirus Disease 2019 Pandemic with Increasing Time Outdoors: The Tokyo Myopia Study.}, journal = {Ophthalmology science}, volume = {4}, number = {5}, pages = {100491}, pmid = {38827490}, issn = {2666-9145}, abstract = {PURPOSE: To investigate the changes in axial length (AL) elongation and other ocular parameters before and during the coronavirus disease 2019 pandemic.

DESIGN: A longitudinal school-based study.

PARTICIPANTS: Public elementary schoolchildren in Tokyo (grades 1-6; age, 6-12 years) participated in this study from 2018 to 2021.

METHODS: All participants underwent eye examinations and provided written consent to measurements of the noncycloplegic refraction and ocular biometry including AL, among others. The students' parents also completed a questionnaire about the students' lifestyles. We included the right eye in our analysis and compared the changes in the ocular parameters among the periods using a linear mixed-effects model for repeated measures and examined the univariate and step-wise multiple regression analyses to evaluate the associations between myopia and other covariates.

MAIN OUTCOME MEASURES: Changes in AL elongation and other ocular parameters from 2018 to 2019 (prepandemic), that of 2019 to 2020 (immediately after the pandemic onset), and that of 2020 to 2021 (during the pandemic).

RESULTS: A total of 578 students before the pandemic period, 432 immediately after the pandemic onset, and 457 during the pandemic period were evaluated. The changes in the ALs and spherical equivalents (SEs) a year before, immediately after onset, and during the pandemic were 0.31 mm/-0.20 diopter, 0.38 mm/-0.27 diopter, and 0.28 mm/-0.47 diopter, respectively (ALs, P < 0.001; SEs, P = 0.014). The results of the questionnaire showed that time spent outdoors daily had changed during the 3 years to 79, 63, and 77 minutes/day, respectively (P < 0.001). Time spent using smartphones or tablets increased year by year to 41, 52, and 62 minutes/day (P < 0.001). The greatest AL elongation occurred during the period when the shortest amount of time was spent outdoors during the 3 years.

CONCLUSIONS: These results suggested that the school closures and decreasing time spent outdoors might have caused greater AL elongation among schoolchildren in Tokyo; however, it is possible that, although the time spent in near work still increased, the return to the time spent outdoors to the prepandemic levels may have affected the slowing of AL elongation after lockdown.

FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, } @article {pmid38826647, year = {2024}, author = {Zhao, H and Xie, J and Chen, Y and Cao, J and Liao, WH and Cao, H}, title = {Diagnosis of neurodegenerative diseases with a refined Lempel-Ziv complexity.}, journal = {Cognitive neurodynamics}, volume = {18}, number = {3}, pages = {1153-1166}, pmid = {38826647}, issn = {1871-4080}, abstract = {The investigation into the distinctive difference of gait is of significance for the clinical diagnosis of neurodegenerative diseases. However, human gait is affected by many factors like behavior, occupation and so on, and they may confuse the gait differences among Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease. For the purpose of examining distinctive gait differences of neurodegenerative diseases, this study extracts various features from both vertical ground reaction force and time intervals. Moreover, refined Lempel-Ziv complexity is proposed considering the detailed distribution of signals based on the median and quartiles. Basic features (mean, coefficient of variance, and the asymmetry index), nonlinear dynamic features (Hurst exponent, correlation dimension, largest Lyapunov exponent), and refined Lempel-Ziv complexity of different neurodegenerative diseases are compared statistically by violin plot and Kruskal-Wallis test to reveal distinction and regularities. The comparative analysis results illustrate the gait differences across these neurodegenerative diseases by basic features and nonlinear dynamic features. Classification results by random forest indicate that the refined Lempel-Ziv complexity can robustly enhance the diagnosis accuracy when combined with basic features.}, } @article {pmid38826483, year = {2024}, author = {Provasek, VE and Kodavati, M and Kim, B and Mitra, J and Hegde, ML}, title = {TDP43 Interacts with MLH1 and MSH6 Proteins in A DNA Damage-Inducible Manner.}, journal = {Research square}, volume = {}, number = {}, pages = {}, pmid = {38826483}, issn = {2693-5015}, support = {R35 CA220430/CA/NCI NIH HHS/United States ; R01 NS094535/NS/NINDS NIH HHS/United States ; P01 CA092584/CA/NCI NIH HHS/United States ; R01 NS088645/NS/NINDS NIH HHS/United States ; R03 AG064266/AG/NIA NIH HHS/United States ; RF1 NS112719/NS/NINDS NIH HHS/United States ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that affects the motor neuron. One aspect of the neuropathology involved in ALS includes increased genomic damage and impaired DNA repair capability. The TAR-DNA binding protein 43 (TDP43) has been associated with both sporadic and familial forms of ALS, and is typically observed as cytosolic mislocalization of protein aggregates, termed TDP43 proteinopathy. TDP43 is a ubiquitous RNA/DNA binding protein with functional implications in a wide range of disease processes, including the repair of DNA double strand breaks (DSBs). While TDP43 is widely known to regulate RNA metabolism, our lab has reported it also functions directly at the protein level to facilitate DNA repair. Here, we show that TDP43 protein interacts with DNA mismatch repair (MMR) proteins MLH1 and MSH6 in a DNA damage-inducible manner. We utilized differentiated SH-SY5Y neuronal cultures to identify this inducible relationship using complimentary approaches of proximity ligation assay (PLA) and co-immunoprecipitation (CoIP) assay. We observed that signals of TDP43 interaction with MLH1 and MSH6 increased significantly following a 2 hr treatment of 10μM methylmethanesulfonate (MMS), a DNA alkylating agent used to induce MMR repair. Likewise, we observed this effect was abolished in cell lines treated with siRNA directed against TDP43. Finally, we demonstrated these protein interactions were significantly increased in lumbar spinal cord samples of ALS-affected patients compared to age-matched controls. These results will inform our future studies to understand the mechanisms and consequences of this TDP43-MMR interaction in the context of ALS affected neurons.}, } @article {pmid38826246, year = {2024}, author = {Martínez, P and Silva, M and Abarzúa, S and Tevy, MF and Jaimovich, E and Constantine-Paton, M and Bustos, FJ and van Zundert, B}, title = {Skeletal myotubes expressing ALS mutant SOD1 induce pathogenic changes, impair mitochondrial axonal transport, and trigger motoneuron death.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2024.05.24.595817}, pmid = {38826246}, issn = {2692-8205}, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the loss of motoneurons (MNs), and despite progress, there is no effective treatment. A large body of evidence shows that astrocytes expressing ALS-linked mutant proteins cause non-cell autonomous toxicity of MNs. Although MNs innervate muscle fibers and ALS is characterized by the early disruption of the neuromuscular junction (NMJ) and axon degeneration, there are controversies about whether muscle contributes to non-cell-autonomous toxicity to MNs. In this study, we generated primary skeletal myotubes from myoblasts derived from ALS mice expressing human mutant SOD1 [G93A] (termed hereafter mutSOD1). Characterization revealed that mutSOD1 skeletal myotubes display intrinsic phenotypic and functional differences compared to control myotubes generated from non-transgenic (NTg) littermates. Next, we analyzed whether ALS myotubes exert non-cell-autonomous toxicity to MNs. We report that conditioned media from mutSOD1 myotubes (mutSOD1-MCM), but not from control myotubes (NTg-MCM), induced robust death of primary MNs in mixed spinal cord cultures and compartmentalized microfluidic chambers. Our study further revealed that applying mutSOD1-MCM to the MN axonal side in microfluidic devices rapidly reduces mitochondrial axonal transport while increasing Ca2+ transients and reactive oxygen species (i.e., H 2 O 2). These results indicate that soluble factor(s) released by mutSOD1 myotubes cause MN axonopathy that leads to lethal pathogenic changes.}, } @article {pmid38826088, year = {2024}, author = {Mehta, P and Raymond, J and Nair, T and Han, M and Punjani, R and Larson, T and Berry, J and Mohidul, S and Horton, DK}, title = {Prevalence of ALS in all 50 states in the United States, data from the National ALS Registry, 2011-2018.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {25}, number = {7-8}, pages = {687-693}, doi = {10.1080/21678421.2024.2358786}, pmid = {38826088}, issn = {2167-9223}, mesh = {*Amyotrophic Lateral Sclerosis/epidemiology ; Humans ; United States/epidemiology ; *Registries ; Male ; Prevalence ; Aged ; Female ; Middle Aged ; Aged, 80 and over ; Adult ; Risk Factors ; }, abstract = {Objective: To summarize the prevalence of ALS in all 50 states and Washington, DC in the United States from 2011 to 2018 using data collected and analyzed by the National ALS Registry. In October 2010, the federal Agency for Toxic Substances and Disease Registry (ATSDR) launched the congressionally mandated Registry to determine the incidence and prevalence of ALS within the USA, characterize the demographics of persons with ALS, and identify the potential risk factors for the disease. This is the first analysis of state-level ALS prevalence estimates. Methods: ALS is not a notifiable disease in the USA, so the Registry uses a two-pronged approach to identify cases. The first approach uses existing national administrative databases (Medicare, Veterans Health Administration, and Veterans Benefits Administration). The second method uses a secure web portal to gather voluntary participant data and identify cases not included in the national administrative databases. Results: State-level age-adjusted average prevalence from 2011-2018 ranged from 2.6 per 100,000 persons (Hawaii) to 7.8 per 100,000 persons (Vermont), with an average of 4.4 per 100,000 persons in the US. New England and Midwest regions had higher prevalence rates than the national average. Conclusions: These findings summarize the prevalence of ALS for all 50 states from 2011 to 2018. This is a continuing effort to identify ALS cases on a national population basis. The establishment of the National ALS Registry has allowed for epidemiological trends of this disease and the assessment of potential risk factors that could cause ALS.}, } @article {pmid38826044, year = {2024}, author = {Rooney, JPK and Geoghegan, G and O'Reilly, F and Heverin, M and Bose-O'Reilly, S and Casale, F and Chio, A and Günther, K and Schuster, J and Klopstock, T and Ludolph, A and Hardiman, O and Rakete, S}, title = {Serum heat shock protein concentrations are not associated with amyotrophic lateral sclerosis risk or survival in three European populations.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {25}, number = {7-8}, pages = {751-759}, doi = {10.1080/21678421.2024.2358805}, pmid = {38826044}, issn = {2167-9223}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/blood/mortality/epidemiology/diagnosis ; Female ; Male ; Middle Aged ; Aged ; *Biomarkers/blood ; Germany/epidemiology ; HSP70 Heat-Shock Proteins/blood ; Ireland/epidemiology ; Italy/epidemiology ; Heat-Shock Proteins/blood ; HSP90 Heat-Shock Proteins/blood ; Cohort Studies ; Adult ; Europe/epidemiology ; }, abstract = {Introduction: Serum heat shock protein (HSP) concentrations have been reported as potential biomarkers for amyotrophic lateral sclerosis (ALS). Here, we investigate the role of serum HSP70, HSP90, and DNAJC7 as biomarkers for ALS. Methods: Serum samples were collected from ALS patients and volunteer controls from three different clinical cohorts (in Germany, Ireland, and Italy). Serum HSP concentrations were determined using enzyme-linked immunosorbent assay. Descriptive statistics, generalized logistic regression, and Cox proportional hazards models were used to model associations between log serum HSP concentrations and ALS risk. Results: In total, 251 ALS patients and 184 healthy volunteers were included. Logistic regression models failed to find associations between ALS risk and log serum concentration of HSP70 (OR 0.43, 95% CI: 0.10-1.78, p = 0.242), HSP90 (OR 0.95, 95% CI: 0.39-2.37, p = 0.904), or DNAJC7 (OR 1.55, 95% CI: 0.90-2.68, p = 0.118). Survival of ALS patients was not associated with log serum concentration of HSP HSP70 (HR1.06, 95% CI: 0.36-3.14, p = 0.916), HSP90 (HR 1.17, 95% CI: 0.67-2.02, p = 0.584), or DNAJC7 (HR 0.83, 95% CI: 0.57-1.21, p = 0.337). Discussion: We did not replicate previous findings that serum HSP70 and HSP90 concentrations were associated with risk of ALS. DNAJC7 was not associated with ALS risk, and there were no obvious longitudinal patterns in log serum concentrations of HSP70, HSP90, or DNAJC7. In addition, serum HSP concentrations were not associated with ALS survival.}, } @article {pmid38825034, year = {2024}, author = {Fang, T and Pacut, P and Bose, A and Sun, Y and Gao, J and Sivakumar, S and Bloom, B and Nascimento Andrade, EI and Trombetta, B and Ghasemi, M}, title = {Clinical and genetic factors affecting diagnostic timeline of amyotrophic lateral sclerosis: a 15-year retrospective study.}, journal = {Neurological research}, volume = {46}, number = {9}, pages = {859-867}, doi = {10.1080/01616412.2024.2362578}, pmid = {38825034}, issn = {1743-1328}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/diagnosis ; Male ; Female ; Middle Aged ; Retrospective Studies ; Aged ; Genetic Testing/methods ; Adult ; Delayed Diagnosis ; Time Factors ; }, abstract = {OBJECTIVES: Amyotrophic Lateral Sclerosis (ALS) diagnosis can take 10-16 months from symptom onset, leading to delays in treatment and patient counselling. We studied the impact of clinical and genetic risk factors on the diagnostic timeline of ALS.

METHODS: Baseline characteristics, family history, gene testing, onset location, time from symptom onset to diagnosis, and time from first doctor visit to suspected ALS was collected. We used multiple regression to assess the interaction of these factors on ALS diagnostic timeline. We analysed a subgroup of patients with genetic testing and compared positive or negative tests, sporadic or familial and ALS-related genes to time for diagnosis.

RESULTS: Four hundred and forty-eight patients diagnosed with ALS at the University of Massachusetts Chan Medical Center between January 2007 and December 2021 were analysed. The median time to ALS diagnosis was 12 months and remained unchanged from 2007 to 2021 (p = 0.20). Diagnosis was delayed in patients with sporadic compared with familial ALS (mean months [standard deviation], 16.5[13.5] and 11.2[8.5], p < 0.001); cognitive onset (41[21.26]) had longer time to diagnosis than bulbar (11.9[8.2]), limb (15.9[13.2]), respiratory (19.7[13.9]) and ALS with multiple onset locations (20.77[15.71], p < 0.001). One hundred and thirty-four patients had gene testing and 32 tested positive (23.8%). Gene testing (p = 0.23), a positive genetic test (p = 0.16), different ALS genes (p = 0.25) and sporadic (p = 0.92) or familial (p = 0.85) ALS testing positive for ALS genes did not influence time to diagnosis.

DISCUSSION: Time for ALS diagnosis remained unchanged from 2007 to 2021, bulbar-onset and familial ALS made for faster diagnosis.}, } @article {pmid38824664, year = {2024}, author = {Ahmed, Z and Shahzadi, K and Jin, Y and Li, R and Momanyi, BM and Zulfiqar, H and Ning, L and Lin, H}, title = {[Not Available].}, journal = {Proteomics}, volume = {24}, number = {21-22}, pages = {e2400044}, doi = {10.1002/pmic.202400044}, pmid = {38824664}, issn = {1615-9861}, support = {62372088//National Natural Science Foundation of China/ ; }, mesh = {*RNA/metabolism ; Humans ; *Artificial Intelligence ; Proteins/metabolism/chemistry/analysis ; Databases, Protein ; Computational Biology/methods ; Phase Separation ; }, abstract = {RNA-dependent liquid-liquid phase separation (LLPS) proteins play critical roles in cellular processes such as stress granule formation, DNA repair, RNA metabolism, germ cell development, and protein translation regulation. The abnormal behavior of these proteins is associated with various diseases, particularly neurodegenerative disorders like amyotrophic lateral sclerosis and frontotemporal dementia, making their identification crucial. However, conventional biochemistry-based methods for identifying these proteins are time-consuming and costly. Addressing this challenge, our study developed a robust computational model for their identification. We constructed a comprehensive dataset containing 137 RNA-dependent and 606 non-RNA-dependent LLPS protein sequences, which were then encoded using amino acid composition, composition of K-spaced amino acid pairs, Geary autocorrelation, and conjoined triad methods. Through a combination of correlation analysis, mutual information scoring, and incremental feature selection, we identified an optimal feature subset. This subset was used to train a random forest model, which achieved an accuracy of 90% when tested against an independent dataset. This study demonstrates the potential of computational methods as efficient alternatives for the identification of RNA-dependent LLPS proteins. To enhance the accessibility of the model, a user-centric web server has been established and can be accessed via the link: http://rpp.lin-group.cn.}, } @article {pmid38823272, year = {2024}, author = {Bijl, I and Vianen, NJ and Van Lieshout, EMM and Beekers, CHJ and Van Der Waarden, NWPL and Pekbay, B and Maissan, IM and Verhofstad, MHJ and Van Vledder, MG}, title = {Emergency reflex action drill for traumatic cardiac arrest in a simulated pre-hospital setting; a one-group pre-post intervention study.}, journal = {Intensive & critical care nursing}, volume = {84}, number = {}, pages = {103731}, doi = {10.1016/j.iccn.2024.103731}, pmid = {38823272}, issn = {1532-4036}, mesh = {Humans ; Prospective Studies ; Female ; Adult ; *Emergency Medical Services/methods/standards/statistics & numerical data ; Male ; Heart Arrest/complications/therapy ; Middle Aged ; Simulation Training/methods/standards ; Patient Simulation ; }, abstract = {BACKGROUND: Emergency Reflex Action Drills (ERADs) are meant to decrease stress-associated cognitive demand in high urgency situations. The aim of this study was to develop and test an ERAD for witnessed traumatic cardiac arrest (TCA), an event in which potentially reversible causes need to be systematically addressed and treated in a short period of time. We hypothesize that this ERAD (the TCA-Drill) helps ground Emergency Medical Services (EMS) nurses in overcoming performance decline during this specific high-pressure situation.

METHODS: This was a prospective, experimental one-group pre-post intervention study. Ground EMS nurses participated in a session of four simulated scenarios, with an in-between educational session to teach the TCA-Drill. Scenarios were video recorded, after which adherence and time differences were analyzed. Self-confidence on clinical practice was measured before and after the scenarios.

RESULTS: Twelve ground EMS nurses participated in this study. Overall median time to address reversible causes of TCA decreased significantly using the TCA-Drill (132 vs. 110 s; p = 0.030) compared with the conventional ALS strategy. More specifically, participants adhering to the TCA-Drill showed a significantly lower time needed for hemorrhage control (58 vs. 37 s; p = 0.012). Eight of 12 (67 %) ground EMS nurses performed the ERAD without protocol deviations. Reported self-confidence significantly increased on 11 of the 13 surveyed items.

CONCLUSIONS: The use of an ERAD for TCA (the TCA-Drill) significantly reduces the time to address reversible causes for TCA without delaying chest compressions in a simulated environment and can be easily taught to ground EMS nurses and increases self-confidence.

The use of an ERAD for TCA (the TCA-Drill can significantly reduce the time to address reversible causes for TCA without delaying chest compression. This drill can be easily taught to ground EMS nurses and increases their self-confidence in addressing TCA-patients.}, } @article {pmid38823229, year = {2024}, author = {Roman-Pognuz, E and Rigutti, S and Colussi, G and Lena, E and Bonsano, M and Lucangelo, U}, title = {Acute esophageal necrosis following cardiac arrest: A rare and lethal syndrome with diagnostic challenges.}, journal = {International journal of surgery case reports}, volume = {120}, number = {}, pages = {109751}, pmid = {38823229}, issn = {2210-2612}, abstract = {Acute esophageal necrosis (AEN) is a condition characterized by the necrosis of the distal portion of the esophageal mucosa. Risk factors predisposing to this condition are associated to compromised vascular perfusion (e.g. diabetes mellitus, chronic kidney disease, advanced age, and hypertension, shock states). Complications of AEN can be severe including UGI stricture, perforation and overall increased mortality. The true incidence of AEN remains uncertain due to potential subclincal presentations and early resolution.

CASE PRESENTATION: The case outlined involves a 66-years-old obese male with history of alcoholism and lymph-edema of the left leg who presented to the emergency department with hematemesis, haemodynamic instability and impaired consciousness. Shortly after initial assessment, the patient went into cardiac arrest with pulse-less electrical activity (PEA). Return of spontaneous circulation (ROSC) was achieved following instigation of ALS protocol, fluid resuscitation and the administration of a total of 5 mg of adrenaline. Following stabilization, a CT scan was performed which reported a moderately enlarged esophagus with a thickened wall, liquid hypodense material within the esophagus and stomach, and liver cirrhosis. The emergent esophagogastroduodenoscopy (EGDS) revealed extensive mucosal findings indicative of diffuse necrosis with initial scarring, which was later diagnosed as AEN. The patient unfortunately deceased in ICU after developing progression of the AEN, post-cardiac arrest syndrome and liver failure.

CLINICAL DISCUSSION: The presented case highlights several crucial clinical issues and management problems related to AEN. To diagnose AEN, EGDS is still the gold-standard since it allows direct inspection of the esophageal mucosal layer. The management of AEN necessitates a multidisciplinary approach that includes aggressive resuscitation, treatment of underlying comorbidities, and supportive care (e.g. proton pump inhibitors). The mortality rate for AEN remains high despite improvements in diagnosis and treatment highlighting the need to recognize this condition early and intervene promptly in the patients affected. Moreover, long-term sequelae like stricture formation of the esophagus and impaired esophageal motility may contribute to morbidity requiring continuos monitoring. Therefore, to optimize outcomes while reducing complications among affected patients, prompt identification associated with appropriate medical measures are essential. More research needs to be done aiming to better understand the pathophysiology of AEN thereby identifying strategies for its prevention or cure.

CONCLUSIONS: AEN is a rare syndrome characterized by upper gastrointestinal bleeding and hypoxic damage of the esophageal mucosa, often associated with ischemia, gastric outlet obstruction, and compromised protective barriers. Treatment involves aggressive resuscitation, proton pump inhibitors, and monitoring for infection or perforation. However, despite intensive efforts, the mortality rate for AEN remains high at 32 %.}, } @article {pmid38822985, year = {2024}, author = {Faysal, M and Dehbia, Z and Zehravi, M and Sweilam, SH and Haque, MA and Kumar, KP and Chakole, RD and Shelke, SP and Sirikonda, S and Nafady, MH and Khan, SL and Nainu, F and Ahmad, I and Emran, TB}, title = {Flavonoids as Potential Therapeutics Against Neurodegenerative Disorders: Unlocking the Prospects.}, journal = {Neurochemical research}, volume = {49}, number = {8}, pages = {1926-1944}, pmid = {38822985}, issn = {1573-6903}, mesh = {*Flavonoids/therapeutic use/pharmacology ; Humans ; *Neurodegenerative Diseases/drug therapy ; Animals ; Neuroprotective Agents/therapeutic use/pharmacology ; Oxidative Stress/drug effects ; Antioxidants/therapeutic use/pharmacology ; }, abstract = {Neurodegeneration, the decline of nerve cells in the brain, is a common feature of neurodegenerative disorders (NDDs). Oxidative stress, a key factor in NDDs such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease can lead to neuronal cell death, mitochondria impairment, excitotoxicity, and Ca[2+] stress. Environmental factors compromising stress response lead to cell damage, necessitating novel therapeutics for preventing or treating brain disorders in older individuals and an aging population. Synthetic medications offer symptomatic benefits but can have adverse effects. This research explores the potential of flavonoids derived from plants in treating NDDs. Flavonoids compounds, have been studied for their potential to enter the brain and treat NDDs. These compounds have diverse biological effects and are currently being explored for their potential in the treatment of central nervous system disorders. Flavonoids have various beneficial effects, including antiviral, anti-allergic, antiplatelet, anti-inflammatory, anti-tumor, anti-apoptotic, and antioxidant properties. Their potential to alleviate symptoms of NDDs is significant.}, } @article {pmid38822416, year = {2024}, author = {Yadav, S and Deepika, and Moar, K and Kumar, A and Khola, N and Pant, A and Kakde, GS and Maurya, PK}, title = {Reconsidering red blood cells as the diagnostic potential for neurodegenerative disorders.}, journal = {Biology of the cell}, volume = {116}, number = {7}, pages = {e2400019}, doi = {10.1111/boc.202400019}, pmid = {38822416}, issn = {1768-322X}, support = {//Council of Scientific and Industrial Research (CSIR), Government of India/ ; //University Grant Commission (UGC)/ ; HSCIT-3946//Haryana State Council for Science, Innovation, and Technology/ ; //Central University of Haryana, Mahendergarh/ ; //Indian Council of Medical Research (ICMR), Government of India/ ; }, mesh = {Humans ; *Erythrocytes/metabolism ; *Neurodegenerative Diseases/diagnosis/metabolism/blood ; *Biomarkers/metabolism/blood ; Oxidative Stress ; Animals ; Alzheimer Disease/diagnosis/metabolism/blood ; }, abstract = {BACKGROUND: Red blood cells (RBCs) are usually considered simple cells and transporters of gases to tissues.

HYPOTHESIS: However, recent research has suggested that RBCs may have diagnostic potential in major neurodegenerative disorders (NDDs).

RESULTS: This review summarizes the current knowledge on changes in RBC in Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and other NDDs. It discusses the deposition of neuronal proteins like amyloid-β, tau, and α-synuclein, polyamines, changes in the proteins of RBCs like band-3, membrane transporter proteins, heat shock proteins, oxidative stress biomarkers, and altered metabolic pathways in RBCs during neurodegeneration. It also highlights the comparison of RBC diagnostic markers to other in-market diagnoses and discusses the challenges in utilizing RBCs as diagnostic tools, such as the need for standardized protocols and further validation studies.

SIGNIFICANCE STATEMENT: The evidence suggests that RBCs have diagnostic potential in neurodegenerative disorders, and this study can pave the foundation for further research which may lead to the development of novel diagnostic approaches and treatments.}, } @article {pmid38821351, year = {2024}, author = {Pocock, J and Vasilopoulou, F and Svensson, E and Cosker, K}, title = {Microglia and TREM2.}, journal = {Neuropharmacology}, volume = {257}, number = {}, pages = {110020}, doi = {10.1016/j.neuropharm.2024.110020}, pmid = {38821351}, issn = {1873-7064}, mesh = {Humans ; *Microglia/metabolism ; *Receptors, Immunologic/metabolism/genetics ; *Membrane Glycoproteins/metabolism/genetics ; Animals ; Neurodegenerative Diseases/metabolism/pathology/genetics ; Induced Pluripotent Stem Cells/metabolism ; Phagocytosis/physiology ; }, abstract = {TREM2 is a membrane receptor solely expressed on microglia in normal brain. In this review we outline recent advances in TREM2 biology and its implications for microglial function, with particular emphasis on findings from iPSC-derived microglia (iMG) expressing TREM2 loss-of-function mutations. Alterations in receptor proximal and distal signalling underlie TREM2 risk variants linked to neurodegenerative disease, principally NH-linked FTD, and late-onset AD, but emerging data suggest roles for TREM2 in PD, MS and ALS. TREM2 downstream functions include phagocytosis of myelin debris, amyloid beta peptides, and phosphatidylserine-expressing cells (resulting from damage or stress). Microglial survival, migration, DAMP signalling, inflammasome activation, and intercellular signalling including tau spreading via exosomes, as well as roles for sTREM2 in protection and as a biomarker are discussed. The role of TREM2 in metabolic homeostasis, and immunometabolic switching are discussed regarding microglial responses to damage and protection. The use of iPSC models to investigate the role of TREM2 in AD, PD, MS, ALS, and other neurodegenerative diseases could prove invaluable due to their ability to recapitulate human pathology, allowing a full understanding of TREM2 and microglial involvement in the underlying disease mechanisms and progression. This article is part of the Special Issue on "Microglia".}, } @article {pmid38820331, year = {2025}, author = {Dessie, G and Li, J and Nghiem, S and Doan, T}, title = {Prevalence and Determinants of Stunting-Anemia and Wasting-Anemia Comorbidities and Micronutrient Deficiencies in Children Under 5 in the Least-Developed Countries: A Systematic Review and Meta-analysis.}, journal = {Nutrition reviews}, volume = {83}, number = {2}, pages = {e178-e194}, pmid = {38820331}, issn = {1753-4887}, support = {//Australia National University/ ; }, mesh = {Child, Preschool ; Female ; Humans ; Infant ; *Anemia/epidemiology ; Comorbidity ; *Developing Countries/statistics & numerical data ; *Growth Disorders/epidemiology ; *Micronutrients/deficiency ; Prevalence ; *Wasting Syndrome/epidemiology ; }, abstract = {CONTEXT: Despite shifting from addressing isolated forms of malnutrition to recognizing its multifaceted nature, evidence on the prevalence and determinants of micronutrient deficiencies, and their coexistence with undernutrition in children under 5, remains insufficient, unsystematic, and incohesive.

OBJECTIVE: The aim of this systematic review and meta-analysis was to assess the prevalence and determinants of stunting-anemia and wasting-anemia comorbidities and micronutrient deficiencies in children under 5 in the least-developed countries (LDCs).

DATA SOURCES: Electronic searches took place from January 15, 2023, to February 14, 2024, across multiple databases, including PubMed, Embase, Web of Science, SCOPUS, African Index Medicus (AIM), World Health Organization's Institutional Repository for Information Sharing (IRIS), and African Journals Online. The search spanned the years 2000 to 2024, yet it yielded eligible full-text English research articles from only 2005 to 2021 conducted in LDCs. Studies lacking quantitative data on malnutrition types and their determinants were excluded.

DATA EXTRACTION: Two independent authors assessed articles for bias and quality using Hoy et al's 10-item scale and Newcastle-Ottawa Scale (NOS) criteria. Prevalence and other details were extracted using a Joanna Briggs Institute Excel template. Authors extracted adjusted odds ratios (aORs) for determinant factors such as sex and vitamin A and iron supplementation.

DATA ANALYSIS: The search yielded 6248 articles from 46 LDCs. Sixty-nine articles, with a total sample size of 181 605, met inclusion criteria for the final meta-analysis. Vitamin A deficiency affected 16.32% of children, and iodine deficiency affected 43.41% of children. The pooled prevalence of wasting-anemia and stunting-anemia comorbidity was 5.44% and 19.47%, respectively. Stunting was associated with vitamin A deficiency (aOR: 1.54; 95% CI: 1.01-2.37), and not taking vitamin A supplementation was associated with iron-deficiency anemia (aOR: 1.37; 95% CI: 1.21-1.55).

CONCLUSION: A significant proportion of children under 5 in LDCs experienced stunting-anemia and wasting-anemia comorbidities and micronutrient deficiencies. This study underscores the urgent need to address factors driving these burdens.

PROSPERO registration no. CRD42023409483.}, } @article {pmid38820149, year = {2024}, author = {Montañana-Rosell, R and Selvan, R and Hernández-Varas, P and Kaminski, JM and Sidhu, SK and Ahlmark, DB and Kiehn, O and Allodi, I}, title = {Spinal inhibitory neurons degenerate before motor neurons and excitatory neurons in a mouse model of ALS.}, journal = {Science advances}, volume = {10}, number = {22}, pages = {eadk3229}, pmid = {38820149}, issn = {2375-2548}, mesh = {*Amyotrophic Lateral Sclerosis/pathology/genetics/metabolism ; Animals ; *Motor Neurons/metabolism/pathology ; *Disease Models, Animal ; Mice ; *Interneurons/metabolism/pathology ; *Spinal Cord/pathology/metabolism ; *Mice, Transgenic ; Superoxide Dismutase-1/genetics/metabolism ; Humans ; Disease Progression ; Nerve Degeneration/pathology ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is characterized by the progressive loss of somatic motor neurons. A major focus has been directed to motor neuron intrinsic properties as a cause for degeneration, while less attention has been given to the contribution of spinal interneurons. In the present work, we applied multiplexing detection of transcripts and machine learning-based image analysis to investigate the fate of multiple spinal interneuron populations during ALS progression in the SOD1[G93A] mouse model. The analysis showed that spinal inhibitory interneurons are affected early in the disease, before motor neuron death, and are characterized by a slow progressive degeneration, while excitatory interneurons are affected later with a steep progression. Moreover, we report differential vulnerability within inhibitory and excitatory subpopulations. Our study reveals a strong interneuron involvement in ALS development with interneuron specific degeneration. These observations point to differential involvement of diverse spinal neuronal circuits that eventually may be determining motor neuron degeneration.}, } @article {pmid38819717, year = {2024}, author = {Tappenden, P and Hardiman, O and Kwon, SH and Mon-Yee, M and Galvin, M and McDermott, C and , }, title = {A Model-Based Economic Evaluation of Hypothetical Treatments for Amyotrophic Lateral Sclerosis in the UK: Implications for Pricing of New and Emerging Health Technologies.}, journal = {PharmacoEconomics}, volume = {42}, number = {9}, pages = {1003-1016}, pmid = {38819717}, issn = {1179-2027}, mesh = {*Amyotrophic Lateral Sclerosis/economics/therapy/drug therapy ; Humans ; *Cost-Benefit Analysis ; *Quality-Adjusted Life Years ; United Kingdom ; *Models, Economic ; Disease Progression ; Biomedical Technology/economics ; Technology Assessment, Biomedical ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a devastating disease which leads to loss of muscle function and paralysis. Historically, clinical drug development has been unsuccessful, but promising disease-modifying therapies (DMTs) may be on the horizon.

OBJECTIVES: The aims of this study were to estimate survival, quality-adjusted life-years (QALYs) and costs under current care, and to explore the conditions under which new therapies might be considered cost effective.

METHODS: We developed a health economic model to evaluate the cost effectiveness of future ALS treatments from a UK National Health Service and Personal Social Services perspective over a lifetime horizon using data from the ALS-CarE study. Costs were valued at 2021/22 prices. Two hypothetical interventions were evaluated: a DMT which delays progression and mortality, and a symptomatic therapy which improves utility only. Sensitivity analysis was conducted to identify key drivers of cost effectiveness.

RESULTS: Starting from King's stage 2, patients receiving current care accrue an estimated 2.27 life-years, 0.75 QALYs and lifetime costs of £68,047. Assuming a 50% reduction in progression rates and a UK-converted estimate of the price of edaravone, the incremental cost-effectiveness ratio for a new DMT versus current care is likely to exceed £735,000 per QALY gained. Symptomatic therapies may be more likely to achieve acceptable levels of cost effectiveness.

CONCLUSIONS: Regardless of efficacy, DMTs may struggle to demonstrate cost effectiveness, even at a low price. The cost effectiveness of DMTs is likely to be strongly influenced by drug price, the magnitude and durability of relative treatment effects, treatment starting/stopping rules and any additional utility benefits over current care.}, } @article {pmid38819491, year = {2024}, author = {Juarez, D and Handal-Silva, A and Morán-Perales, JL and Torres-Cifuentes, DM and Flores, G and Treviño, S and Moreno-Rodriguez, A and Guevara, J and Diaz, A}, title = {New insights into sodium phenylbutyrate as a pharmacotherapeutic option for neurological disorders.}, journal = {Synapse (New York, N.Y.)}, volume = {78}, number = {4}, pages = {e22301}, doi = {10.1002/syn.22301}, pmid = {38819491}, issn = {1098-2396}, support = {IN214117//PAPITT-UNAM/ ; DIFA-NAT24-G//Vicerrectoría de Investigación y Estudios de Posgrado, Benemérita Universidad Autónoma de Puebla/ ; TEMS-NAT24-G//Vicerrectoría de Investigación y Estudios de Posgrado, Benemérita Universidad Autónoma de Puebla/ ; }, mesh = {Humans ; *Phenylbutyrates/therapeutic use/pharmacology ; Animals ; *Nervous System Diseases/drug therapy/metabolism ; }, abstract = {Neurological disorders (NDs) are diseases of the central and peripheral nervous systems that affect more than one billion people worldwide. The risk of developing an ND increases with age due to the vulnerability of the different organs and systems to genetic, environmental, and social changes that consequently cause motor and cognitive deficits that disable the person from their daily activities and individual and social productivity. Intrinsic factors (genetic factors, age, gender) and extrinsic factors (addictions, infections, or lifestyle) favor the persistence of systemic inflammatory processes that contribute to the evolution of NDs. Neuroinflammation is recognized as a common etiopathogenic factor of ND. The study of new pharmacological options for the treatment of ND should focus on improving the characteristic symptoms and attacking specific molecular targets that allow the delay of damage processes such as neuroinflammation, oxidative stress, cellular metabolic dysfunction, and deregulation of transcriptional processes. In this review, we describe the possible role of sodium phenylbutyrate (NaPB) in the pathogenesis of Alzheimer's disease, hepatic encephalopathy, aging, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis; in addition, we describe the mechanism of action of NaPB and its beneficial effects that have been shown in various in vivo and in vitro studies to delay the evolution of any ND.}, } @article {pmid38819416, year = {2024}, author = {Finsterer, J}, title = {Sleep Disorders Can Only be a Risk Factor for Breathing Disorders in Amyotrophic Lateral Sclerosis if All Other Risk Factors are Excluded.}, journal = {Annals of Indian Academy of Neurology}, volume = {27}, number = {4}, pages = {450-451}, pmid = {38819416}, issn = {0972-2327}, } @article {pmid38819224, year = {2024}, author = {Shen, J and Gu, X and Xiao, C and Yan, H and Feng, Y and Li, X}, title = {Genome-wide association analysis reveals potential genetic correlation and causality between circulating inflammatory proteins and amyotrophic lateral sclerosis.}, journal = {Aging}, volume = {16}, number = {11}, pages = {9470-9484}, pmid = {38819224}, issn = {1945-4589}, mesh = {*Amyotrophic Lateral Sclerosis/genetics/blood ; Humans ; *Genome-Wide Association Study ; *Genetic Predisposition to Disease ; Polymorphism, Single Nucleotide ; Mendelian Randomization Analysis ; Genetic Pleiotropy ; Inflammation/genetics/blood ; }, abstract = {BACKGROUND: Amyotrophic Lateral Sclerosis (ALS), a fatal neurodegenerative disease, continues to elude complete comprehension of its pathological underpinnings. Recent focus on inflammation in ALS pathogenesis prompts this investigation into the genetic correlation and potential causal relationships between circulating inflammatory proteins and ALS.

METHODS: Genome-wide association study (GWAS) data encompassing 91 circulating inflammatory protein measures from 14,824 individuals of European ancestry, alongside records from 27,205 ALS cases and 110,881 controls, were employed. Assessment of genetic correlation and overlap utilized LD score regression (LDSC), high-definition likelihood (HDL), and genetic analysis integrating pleiotropy and annotation (GPA) methodologies. Identification of shared genetic loci involved pleiotropy analysis, functional mapping and annotation (FUMA), and co-localization analysis. Finally, Mendelian randomization was applied to probe causal relationships between inflammatory proteins and ALS.

RESULTS: Our investigation revealed significant genetic correlation and overlap between ALS and various inflammatory proteins, including C-C motif chemokine 28, Interleukin-18, C-X-C motif chemokine 1, and Leukemia inhibitory factor receptor (LIFR). Pleiotropy analysis uncovered shared variations at specific genetic loci, some of which bore potential harm. Mendelian randomization analysis suggested that alterations in specific inflammatory protein levels, notably LIFR, could impact ALS risk.

CONCLUSIONS: Our findings uncover a genetic correlation between certain circulating inflammatory proteins and ALS, suggesting their possible causal involvement in ALS pathogenesis. Moreover, the identification of LIFR as a crucial protein may yield new insights into ALS pathomechanisms and offer a promising avenue for therapeutic interventions. These discoveries provide novel perspectives for advancing the comprehension of ALS pathophysiology and exploring potential therapeutic avenues.}, } @article {pmid38818523, year = {2024}, author = {Shen, J and Wang, X and Wang, M and Zhang, H}, title = {Potential molecular mechanism of exercise reversing insulin resistance and improving neurodegenerative diseases.}, journal = {Frontiers in physiology}, volume = {15}, number = {}, pages = {1337442}, pmid = {38818523}, issn = {1664-042X}, abstract = {Neurodegenerative diseases are debilitating nervous system disorders attributed to various conditions such as body aging, gene mutations, genetic factors, and immune system disorders. Prominent neurodegenerative diseases include Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and multiple sclerosis. Insulin resistance refers to the inability of the peripheral and central tissues of the body to respond to insulin and effectively regulate blood sugar levels. Insulin resistance has been observed in various neurodegenerative diseases and has been suggested to induce the occurrence, development, and exacerbation of neurodegenerative diseases. Furthermore, an increasing number of studies have suggested that reversing insulin resistance may be a critical intervention for the treatment of neurodegenerative diseases. Among the numerous measures available to improve insulin sensitivity, exercise is a widely accepted strategy due to its convenience, affordability, and significant impact on increasing insulin sensitivity. This review examines the association between neurodegenerative diseases and insulin resistance and highlights the molecular mechanisms by which exercise can reverse insulin resistance under these conditions. The focus was on regulating insulin resistance through exercise and providing practical ideas and suggestions for future research focused on exercise-induced insulin sensitivity in the context of neurodegenerative diseases.}, } @article {pmid38817709, year = {2024}, author = {Ghaderi, S and Batouli, SAH and Kalra, S and Mohammadi, S and Fatehi, F}, title = {A 65-year-old woman with ALS and bilateral precentral motor band sign.}, journal = {Clinical case reports}, volume = {12}, number = {6}, pages = {e9014}, pmid = {38817709}, issn = {2050-0904}, abstract = {Advanced MRI techniques, including SWI, MinIP, and QSM, are instrumental in detecting the "motor band sign" in ALS, aiding in the early diagnosis and assessment of upper motor neuron involvement, which is critical for therapeutic interventions.}, } @article {pmid38817347, year = {2024}, author = {Du, R and Zhu, Y and Chen, P and Li, M and Zhang, Y and Huang, X}, title = {Causal association between obstructive sleep apnea and amyotrophic lateral sclerosis: a Mendelian randomization study.}, journal = {Frontiers in aging neuroscience}, volume = {16}, number = {}, pages = {1357070}, pmid = {38817347}, issn = {1663-4365}, abstract = {BACKGROUND: Obstructive sleep apnea (OSA) had a high prevalence in the population. Whether OSA increases the risk of amyotrophic lateral sclerosis (ALS) is unknown. Our aim was to clarify this issue using two-sample Mendelian randomization (MR) analysis in a large cohort.

METHODS: Two-sample MR was used to evaluate the potential causality between OSA and ALS by selecting single-nucleotide polymorphisms (SNPs) as instrumental variables (IVs) from genome-wide association studies (GWAS). The inverse-variance weighted (IVW) method was chosen as the primary method to estimate causal association. Weighted median, weighted mode and simple mode methods were used as sensitivity analyses to ensure the robustness of the results.

RESULTS: In MR analysis, IVW mode showed genetic liability to OSA was found to be significantly associated with a higher ALS risk (OR, 1.220; 95% confidence interval, 1.031-1.443; p = 0.021). No evidence of heterogeneity and horizontal pleiotropy were suggested.

CONCLUSION: We found potential evidence for a causal effect of OSA on an increased risk of ALS.}, } @article {pmid38816946, year = {2024}, author = {Karas, M and Olsen, J and Straczkiewicz, M and Johnson, SA and Burke, KM and Iwasaki, S and Lahav, A and Scheier, ZA and Clark, AP and Iyer, AS and Huang, E and Berry, JD and Onnela, JP}, title = {Tracking amyotrophic lateral sclerosis disease progression using passively collected smartphone sensor data.}, journal = {Annals of clinical and translational neurology}, volume = {11}, number = {6}, pages = {1380-1392}, pmid = {38816946}, issn = {2328-9503}, support = {//The research reported in this paper was financially supported in part by a grant from Mitsubishi Tanabe Pharma Holdings America, Inc. (MTPHA)./ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology/diagnosis ; *Smartphone ; Male ; Female ; Middle Aged ; *Disease Progression ; Aged ; *Accelerometry/instrumentation ; Mobile Applications ; Walking/physiology ; Exercise/physiology ; }, abstract = {BACKGROUND: Passively collected smartphone sensor data provide an opportunity to study physical activity and mobility unobtrusively over long periods of time and may enable disease monitoring in people with amyotrophic lateral sclerosis (PALS).

METHODS: We enrolled 63 PALS who used Beiwe mobile application that collected their smartphone accelerometer and GPS data and administered the self-entry ALS Functional Rating Scale-Revised (ALSFRS-RSE) survey. We identified individual steps from accelerometer data and used the Activity Index to summarize activity at the minute level. Walking, Activity Index, and GPS outcomes were then aggregated into day-level measures. We used linear mixed effect models (LMMs) to estimate baseline and monthly change for ALSFRS-RSE scores (total score, subscores Q1-3, Q4-6, Q7-9, Q10-12) and smartphone sensor data measures, as well as the associations between them.

FINDINGS: The analytic sample (N = 45) was 64.4% male with a mean age of 60.1 years. The mean observation period was 292.3 days. The ALSFRS-RSE total score baseline mean was 35.8 and had a monthly rate of decline of -0.48 (p-value <0.001). We observed statistically significant change over time and association with ALSFRS-RSE total score for four smartphone sensor data-derived measures: walking cadence from top 1 min and log-transformed step count, step count from top 1 min, and Activity Index from top 1 min.

INTERPRETATION: Smartphone sensors can unobtrusively track physical changes in PALS, potentially aiding disease monitoring and future research.}, } @article {pmid38816580, year = {2024}, author = {Wu, Y and Zheng, W and Xu, G and Zhu, L and Li, Z and Chen, J and Wang, L and Chen, S}, title = {C9orf72 controls hepatic lipid metabolism by regulating SREBP1 transport.}, journal = {Cell death and differentiation}, volume = {31}, number = {8}, pages = {1070-1084}, pmid = {38816580}, issn = {1476-5403}, mesh = {Humans ; *C9orf72 Protein/metabolism/genetics ; *Lipid Metabolism ; *Sterol Regulatory Element Binding Protein 1/metabolism/genetics ; Animals ; *Endoplasmic Reticulum/metabolism ; *Liver/metabolism ; Monomeric GTP-Binding Proteins/metabolism/genetics ; Mice ; COP-Coated Vesicles/metabolism ; Vesicular Transport Proteins/metabolism/genetics ; Lipogenesis/genetics ; }, abstract = {Sterol regulatory element binding transcription factors (SREBPs) play a crucial role in lipid homeostasis. They are processed and transported to the nucleus via COPII, where they induce the expression of lipogenic genes. COPII maintains the homeostasis of organelles and plays an essential role in the protein secretion pathways in eukaryotes. The formation of COPII begins at endoplasmic reticulum exit sites (ERES), and is regulated by SEC16A, which provides a platform for the assembly of COPII. However, there have been few studies on the changes in SEC16A protein levels. The repetitive expansion of the hexanucleotide sequence GGGGCC within the chromosome 9 open reading frame 72 (C9orf72) gene is a prevalent factor in the development of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Here, we found that the absence of C9orf72 leads to a decrease in SEC16A protein levels, resulting in reduced localization of the guanine nucleotide exchange factor SEC12 at the ERES. Consequently, the small GTP binding protein SAR1 is unable to bind the endoplasmic reticulum normally, impairing the assembly of COPII. Ultimately, the disruption of SREBPs transport decreases de novo lipogenesis. These results suggest that C9orf72 acts as a novel role in regulating lipid homeostasis and may serve as a potential therapeutic target for obesity.}, } @article {pmid38816479, year = {2024}, author = {Mathis, S and Beauvais, D and Duval, F and Solé, G and Le Masson, G}, title = {The various forms of hereditary motor neuron disorders and their historical descriptions.}, journal = {Journal of neurology}, volume = {271}, number = {7}, pages = {3978-3990}, pmid = {38816479}, issn = {1432-1459}, mesh = {Humans ; *Motor Neuron Disease/history/genetics ; History, 20th Century ; History, 19th Century ; Spastic Paraplegia, Hereditary/genetics/history ; }, abstract = {Motor neuron disorders comprise a clinically and pathologically heterogeneous group of neurologic diseases characterized by progressive degeneration of motor neurons (including both sporadic and hereditary diseases), affecting the upper motor neurons, lower motor neurons, or both. Hereditary motor neuron disorders themselves represent a vast and heterogeneous group, with numerous clinical and genetic overlaps that can be a source of error. This narrative review aims at providing an overview of the main types of inherited motor neuron disorders by recounting the stages in their historical descriptions. For practical purposes, this review of the literature sets out their various clinical characteristics and updates the list of all the genes involved in the various forms of inherited motor neuron disorders, including spinal muscular atrophy, familial amyotrophic lateral sclerosis, hereditary spastic paraplegia, distal hereditary motor neuropathies/neuronopathies, Kennedy's disease, riboflavin transporter deficiencies, VCPopathy and the neurogenic scapuloperoneal syndrome.}, } @article {pmid38814545, year = {2024}, author = {Sun, S and Chen, Y and Zhao, B and Zhu, J and Wen, T and Peng, B and Ren, Q and Sun, X and Lin, P and Zhang, D and Liu, S}, title = {Abnormal brain functional network dynamics in amyotrophic lateral sclerosis patients with depression.}, journal = {Brain imaging and behavior}, volume = {18}, number = {5}, pages = {1034-1043}, pmid = {38814545}, issn = {1931-7565}, support = {2020M672067//China postdoctoral science foundation/ ; NSFC82001354//National natural science foundation of China/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology/psychology/complications/diagnostic imaging ; Female ; Male ; *Magnetic Resonance Imaging/methods ; Middle Aged ; *Brain/physiopathology/diagnostic imaging ; *Depression/physiopathology/diagnostic imaging ; *Nerve Net/physiopathology/diagnostic imaging ; Adult ; Neural Pathways/physiopathology/diagnostic imaging ; Aged ; Brain Mapping/methods ; }, abstract = {Since depression is common in amyotrophic lateral sclerosis (ALS) patients, we aimed to explore the specific brain functional network dynamics in ALS patients with depression (ALS-D) compared with healthy controls (HCs) and ALS patients without depressive symptoms (ALS-ND). According to the DSM-V, 32 ALS-D patients were selected from a large and newly diagnosed ALS cohort. Then, 32 demographic- and cognitive-matched ALS-ND patients were also selected, and 64 HCs were recruited. These participants underwent resting-state fMRI scans, and functional connectivity state analysis and dynamic graph theory were applied to evaluate brain functional network dynamics. Moreover, the Hamilton Depression Rating Scale (HDRS) was used to quantify depressive symptoms in the ALS-D patients. Four distinct states were identified in the ALS-D patients and controls. Compared with that in HCs, the fraction rate (FR) in state 2 was significantly decreased in ALS-D patients, and the FR in state 4 was significantly increased in ALS-D patients. Compared with that of HCs, the dwell time in state 4 was significantly increased in the ALS-D patients. Moreover, compared with that in the ALS-D patients, the FR in state 3 was significantly decreased in the ALS-ND patients. Among the ALS-D patients, there was the suggestion of a positive association between HDRS scores and dwell time of state 4, but this association did not reach statistical significance (r = 0.354; p = 0.055). Depression is an important feature of ALS patients, and we found a special pattern of brain functional network dynamics in ALS-D patients. Our findings may play an important role in understanding the mechanism underlying depression in ALS patients and help develop therapeutic interventions for depressed ALS patients.}, } @article {pmid38814471, year = {2024}, author = {Costantino, I and Meng, A and Ravits, J}, title = {Alternatively spliced ELAVL3 cryptic exon 4a causes ELAVL3 downregulation in ALS TDP-43 proteinopathy.}, journal = {Acta neuropathologica}, volume = {147}, number = {1}, pages = {93}, pmid = {38814471}, issn = {1432-0533}, support = {T32 AG066596/AG/NIA NIH HHS/United States ; P30 NS047101/RG/CSR NIH HHS/United States ; P30 NS047101/NS/NINDS NIH HHS/United States ; R21 NS121805/NS/NINDS NIH HHS/United States ; T32 AG066596/RG/CSR NIH HHS/United States ; R21 NS121805/RG/CSR NIH HHS/United States ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/pathology/metabolism ; *Alternative Splicing/genetics ; *Exons/genetics ; *Down-Regulation ; TDP-43 Proteinopathies/genetics/pathology/metabolism ; Male ; Female ; Middle Aged ; DNA-Binding Proteins ; }, } @article {pmid38813817, year = {2024}, author = {Sprunger, ML and Jackrel, ME}, title = {The role of Matrin-3 in physiology and its dysregulation in disease.}, journal = {Biochemical Society transactions}, volume = {52}, number = {3}, pages = {961-972}, pmid = {38813817}, issn = {1470-8752}, support = {F31 NS120512/NS/NINDS NIH HHS/United States ; R21 AG080393/AG/NIA NIH HHS/United States ; R35 GM128772/GM/NIGMS NIH HHS/United States ; }, mesh = {Humans ; *RNA-Binding Proteins/metabolism ; *Amyotrophic Lateral Sclerosis/metabolism/genetics ; *Nuclear Matrix-Associated Proteins/metabolism ; *Frontotemporal Dementia/metabolism/genetics ; DNA-Binding Proteins/metabolism ; Animals ; DNA Damage ; RNA-Binding Protein FUS/metabolism/chemistry ; }, abstract = {The dysfunction of many RNA-binding proteins (RBPs) that are heavily disordered, including TDP-43 and FUS, are implicated in amyotrophic lateral sclerosis and frontotemporal dementia (ALS/FTD). These proteins serve many important roles in the cell, and their capacity to form biomolecular condensates (BMCs) is key to their function, but also a vulnerability that can lead to misregulation and disease. Matrin-3 (MATR3) is an intrinsically disordered RBP implicated both genetically and pathologically in ALS/FTD, though it is relatively understudied as compared with TDP-43 and FUS. In addition to binding RNA, MATR3 also binds DNA and is implicated in many cellular processes including the DNA damage response, transcription, splicing, and cell differentiation. It is unclear if MATR3 localizes to BMCs under physiological conditions, which is brought further into question due to its lack of a prion-like domain. Here, we review recent studies regarding MATR3 and its roles in numerous physiological processes, as well as its implication in a range of diseases.}, } @article {pmid38813358, year = {2024}, author = {Finsterer, J}, title = {A positive effect of Cerebrolysin on motor functions and spasticity in ALS with limb or bulbar onset is questionable.}, journal = {Journal of medicine and life}, volume = {17}, number = {2}, pages = {242}, pmid = {38813358}, issn = {1844-3117}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy ; *Muscle Spasticity/drug therapy ; *Amino Acids/therapeutic use/pharmacology ; Neuroprotective Agents/therapeutic use/pharmacology ; }, } @article {pmid38813353, year = {2024}, author = {Firstenfeld, AJ}, title = {A positive effect of Cerebrolysin on motor functions and spasticity in ALS with limb or bulbar onset is questionable.}, journal = {Journal of medicine and life}, volume = {17}, number = {2}, pages = {243}, pmid = {38813353}, issn = {1844-3117}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy ; *Muscle Spasticity/drug therapy ; *Amino Acids/therapeutic use/pharmacology ; Neuroprotective Agents/therapeutic use/pharmacology ; }, } @article {pmid38812975, year = {2024}, author = {Fu, J and Lai, X and Wei, Q and Chen, X and Shang, H}, title = {Associations of cerebrospinal fluid profiles with severity and mortality risk of amyotrophic lateral sclerosis.}, journal = {Frontiers in neuroscience}, volume = {18}, number = {}, pages = {1375892}, pmid = {38812975}, issn = {1662-4548}, abstract = {BACKGROUND: The relationship between routine cerebrospinal fluid (CSF) testing and the disease phenotype of amyotrophic lateral sclerosis (ALS) is unclear, and there are some contradictions in current studies.

METHODS: This study aimed to analyze the relationship between CSF profiles and disease phenotype in ALS patients. We collected 870 ALS patients and 96 control subjects admitted to West China Hospital of Sichuan University. CSF microprotein, albumin, IgG, index of IgG (IgGindex), albumin quotient (QALB), and serum IgG were examined.

RESULTS: In ALS patients, CSF IgG, and QALB were significantly increased, while CSF IgGindex was decreased, compared with control subjects. Approximately one-third of ALS patients had higher CSF IgG levels. The multiple linear regression analysis identified that CSF IgGindex was weakly negatively associated with ALS functional rating scale revised (ALSFRS-R) scores (β = -0.062, p = 0.041). This significance was found in male ALS but not in female ALS. The Cox survival analyses found that upregulated CSF IgG was significantly associated with the increased mortality risk in ALS [HR = 1.219 (1.010-1.470), p = 0.039].

CONCLUSION: In the current study, the higher CFS IgG was associated with increased mortality risk of ALS. CSF IgGindex may be associated with the severity of ALS. These findings may be sex-specific.}, } @article {pmid38812793, year = {2024}, author = {Jadhav, SP}, title = {MicroRNAs in microglia: deciphering their role in neurodegenerative diseases.}, journal = {Frontiers in cellular neuroscience}, volume = {18}, number = {}, pages = {1391537}, pmid = {38812793}, issn = {1662-5102}, abstract = {This review presents a comprehensive analysis of the role of microRNAs in microglia and their implications in the pathogenesis of neurodegenerative diseases. Microglia, as the resident immune cells of the central nervous system (CNS), are pivotal in maintaining neural homeostasis and responding to pathological changes. Recent studies have highlighted the significance of miRNAs, small non-coding RNA molecules, in regulating microglial functions. In neurodegenerative diseases, such as Alzheimer's Disease (AD), Parkinson's Disease (PD), Amyotrophic Lateral Sclerosis (ALS), and Multiple Sclerosis (MS), dysregulated miRNA expression in microglia contributes to disease progression through various mechanisms such regulation of gene expression, as modulation of cytokine response and phagocytosis. This review synthesizes current knowledge on how miRNAs influence microglial activation, cytokine production, and phagocytic activity. Specific miRNAs, such as miR-155, are explored for their roles in modulating microglial responses in the context of neuroinflammation and neurodegeneration. The study also discusses the impact of miRNA dysregulation on the transition of microglia from a neuroprotective to a neurotoxic phenotype, a critical aspect in the progression of neurodegenerative diseases.}, } @article {pmid38812789, year = {2024}, author = {Sidisky, JM and Winters, A and Caratenuto, R and Babcock, DT}, title = {Synaptic defects in a drosophila model of muscular dystrophy.}, journal = {Frontiers in cellular neuroscience}, volume = {18}, number = {}, pages = {1381112}, pmid = {38812789}, issn = {1662-5102}, support = {R01 NS110727/NS/NINDS NIH HHS/United States ; }, abstract = {Muscular dystrophies are a devastating class of diseases that result in a progressive loss of muscle integrity. Duchenne Muscular Dystrophy, the most prevalent form of Muscular Dystrophy, is due to the loss of functional Dystrophin. While much is known regarding destruction of muscle tissue in these diseases, much less is known regarding the synaptic defects that also occur in these diseases. Synaptic defects are also among the earliest hallmarks of neurodegenerative diseases, including the neuromuscular disease Amyotrophic Lateral Sclerosis (ALS). Our current study investigates synaptic defects within adult muscle tissues as well as presynaptic motor neurons in Drosophila dystrophin mutants. Here we demonstrate that the progressive, age-dependent loss of flight ability in dystrophin mutants is accompanied by disorganization of Neuromuscular Junctions (NMJs), including impaired localization of both presynaptic and postsynaptic markers. We show that these synaptic defects, including presynaptic defects within motor neurons, are due to the loss of Dystrophin specifically within muscles. These results should help to better understand the early synaptic defects preceding cell loss in neuromuscular disorders.}, } @article {pmid38811997, year = {2024}, author = {Huang, M and Liu, YU and Yao, X and Qin, D and Su, H}, title = {Variability in SOD1-associated amyotrophic lateral sclerosis: geographic patterns, clinical heterogeneity, molecular alterations, and therapeutic implications.}, journal = {Translational neurodegeneration}, volume = {13}, number = {1}, pages = {28}, pmid = {38811997}, issn = {2047-9158}, mesh = {*Amyotrophic Lateral Sclerosis/genetics/therapy/epidemiology/diagnosis ; Humans ; *Superoxide Dismutase-1/genetics ; Mutation/genetics ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive loss of motor neurons, resulting in global health burden and limited post-diagnosis life expectancy. Although primarily sporadic, familial ALS (fALS) cases suggest a genetic basis. This review focuses on SOD1, the first gene found to be associated with fALS, which has been more recently confirmed by genome sequencing. While informative, databases such as ALSoD and STRENGTH exhibit regional biases. Through a systematic global examination of SOD1 mutations from 1993 to 2023, we found different geographic distributions and clinical presentations. Even though different SOD1 variants are expressed at different protein levels and have different half-lives and dismutase activities, these alterations lead to loss of function that is not consistently correlated with disease severity. Gain of function of toxic aggregates of SOD1 resulting from mutated SOD1 has emerged as one of the key contributors to ALS. Therapeutic interventions specifically targeting toxic gain of function of mutant SOD1, including RNA interference and antibodies, show promise, but a cure remains elusive. This review provides a comprehensive perspective on SOD1-associated ALS and describes molecular features and the complex genetic landscape of SOD1, highlighting its importance in determining diverse clinical manifestations observed in ALS patients and emphasizing the need for personalized therapeutic strategies.}, } @article {pmid38811858, year = {2024}, author = {Benatar, M and Wuu, J and Huey, ED and McMillan, CT and Petersen, RC and Postuma, R and McHutchison, C and Dratch, L and Arias, JJ and Crawley, A and Houlden, H and McDermott, MP and Cai, X and Thakur, N and Boxer, A and Rosen, H and Boeve, BF and Dacks, P and Cosentino, S and Abrahams, S and Shneider, N and Lingor, P and Shefner, J and Andersen, PM and Al-Chalabi, A and Turner, MR and , }, title = {Publisher Correction: The Miami Framework for ALS and related neurodegenerative disorders: an integrated view of phenotype and biology.}, journal = {Nature reviews. Neurology}, volume = {20}, number = {6}, pages = {377}, doi = {10.1038/s41582-024-00978-4}, pmid = {38811858}, issn = {1759-4766}, support = {K01 AG057796/AG/NIA NIH HHS/United States ; R01 AG062268/AG/NIA NIH HHS/United States ; R01 MH120794/MH/NIMH NIH HHS/United States ; U01 AG079850/AG/NIA NIH HHS/United States ; }, } @article {pmid38809826, year = {2024}, author = {Krajewski, E and Lee, J and Viswanathan, N and Olmstead, A and Simmons, Z}, title = {The Effects of Interactive Context on Acoustic Characteristics of Speech in People With Dysarthria: A Preliminary Study.}, journal = {American journal of speech-language pathology}, volume = {33}, number = {4}, pages = {1952-1964}, doi = {10.1044/2024_AJSLP-23-00372}, pmid = {38809826}, issn = {1558-9110}, mesh = {Humans ; *Dysarthria/etiology/physiopathology/diagnosis ; Male ; Female ; *Speech Acoustics ; Middle Aged ; Aged ; *Speech Production Measurement ; *Amyotrophic Lateral Sclerosis/complications/physiopathology ; *Phonetics ; Speech Intelligibility ; Voice Quality ; Preliminary Data ; Sound Spectrography ; Time Factors ; Aged, 80 and over ; Acoustics ; }, abstract = {PURPOSE: The current study compared temporal and spectral acoustic contrast between vowel segments produced by speakers with dysarthria across three speech tasks-interactive, solo habitual, and solo clear.

METHOD: Nine speakers with dysarthria secondary to amyotrophic lateral sclerosis participated in the study. Each speaker was paired with a typical interlocutor over videoconferencing software. The speakers produced the vowels /i, ɪ, ɛ, æ/ in /h/-vowel-/d/ words. For the solo tasks, speakers read the stimuli aloud in both their habitual and clear speaking styles. For the interactive task, speakers produced a target stimulus for their interlocutor to select among the four possibilities. We measured the duration difference between long and short vowels, as well as the F1/F2 Euclidean distance between adjacent vowels, and also determined how well the vowels could be classified based on their acoustic characteristics.

RESULTS: Temporal contrast between long and short vowels was higher in the interactive task than in both solo tasks. Spectral distance between adjacent vowel pairs was also higher for some pairs in the interactive task than the habitual speech task. Finally, vowel classification accuracy was highest in the interactive task.

CONCLUSIONS: Overall, we found evidence that individuals with dysarthria produced vowels with greater acoustic contrast in structured interactions than they did in solo tasks. Furthermore, the speech adjustments they made to the vowel segments differed from those observed in solo speech.}, } @article {pmid38809531, year = {2024}, author = {Yang, CN and Chen, WL and Yeh, HH and Chu, HS and Wu, JH and Hsieh, YT}, title = {Convolutional Neural Network-Based Prediction of Axial Length Using Color Fundus Photography.}, journal = {Translational vision science & technology}, volume = {13}, number = {5}, pages = {23}, pmid = {38809531}, issn = {2164-2591}, mesh = {Humans ; Male ; Female ; *Neural Networks, Computer ; Middle Aged ; Adult ; *Photography/methods ; Aged ; *Axial Length, Eye/diagnostic imaging ; Fundus Oculi ; Young Adult ; Aged, 80 and over ; }, abstract = {PURPOSE: To develop convolutional neural network (CNN)-based models for predicting the axial length (AL) using color fundus photography (CFP) and explore associated clinical and structural characteristics.

METHODS: This study enrolled 1105 fundus images from 467 participants with ALs ranging from 19.91 to 32.59 mm, obtained at National Taiwan University Hospital between 2020 and 2021. The AL measurements obtained from a scanning laser interferometer served as the gold standard. The accuracy of prediction was compared among CNN-based models with different inputs, including CFP, age, and/or sex. Heatmaps were interpreted by integrated gradients.

RESULTS: Using age, sex, and CFP as input, the mean ± standard deviation absolute error (MAE) for AL prediction by the model was 0.771 ± 0.128 mm, outperforming models that used age and sex alone (1.263 ± 0.115 mm; P < 0.001) and CFP alone (0.831 ± 0.216 mm; P = 0.016) by 39.0% and 7.31%, respectively. The removal of relatively poor-quality CFPs resulted in a slight MAE reduction to 0.759 ± 0.120 mm without statistical significance (P = 0.24). The inclusion of age and CFP improved prediction accuracy by 5.59% (P = 0.043), while adding sex had no significant improvement (P = 0.41). The optic disc and temporal peripapillary area were highlighted as the focused areas on the heatmaps.

CONCLUSIONS: Deep learning-based prediction of AL using CFP was fairly accurate and enhanced by age inclusion. The optic disc and temporal peripapillary area may contain crucial structural information for AL prediction in CFP.

TRANSLATIONAL RELEVANCE: This study might aid AL assessments and the understanding of the morphologic characteristics of the fundus related to AL.}, } @article {pmid38809094, year = {2024}, author = {Gafni, R and Nassar, JA and Matzrafi, M and Blank, L and Eizenberg, H}, title = {Unraveling the reasons for failure to control Amaranthus albus: insights into herbicide application at different growth stages, temperature effect, and herbicide resistance on a regional scale.}, journal = {Pest management science}, volume = {80}, number = {9}, pages = {4757-4769}, doi = {10.1002/ps.8192}, pmid = {38809094}, issn = {1526-4998}, support = {132187417//Chief Scientist, Israel Ministry of Agriculture and Rural Development/ ; }, mesh = {*Amaranthus/drug effects/growth & development/genetics ; *Herbicide Resistance/genetics ; *Herbicides/pharmacology ; *Temperature ; *Acetolactate Synthase/metabolism/genetics ; Weed Control/methods ; Israel ; Triazines ; }, abstract = {BACKGROUND: This study investigates factors contributing Amaranthus albus control failure in processing tomato fields in northern Israel. The study region is characterized by a significant climate gradient from east to west, providing the opportunity to investigate the effect of critical elements of the agricultural environment, e.g., temperature. Eight populations were collected from commercial fields in this region. Post-emergence herbicide efficacy of metribuzin, a photosystem II inhibitor, and rimsulfuron, an acetolactate synthase (ALS) inhibitor, was assessed through dose-response analyses at various growth stages. Temperature effects on control efficacy and resistance mechanisms were also explored.

RESULTS: Standard metribuzin dose (X) was ineffective on A. albus plants with more than six true-leaves, whereas 2X dose proved effective. Rimsulfuron at 16X dose was ineffective on plants with more than four true-leaves. We report here the first case of target site resistance to ALS inhibitors in A. albus, due to point mutation in the ALS gene (Pro197 to Leu). Furthermore, our findings suggest potential involvement of CYT P450 enzymes in enhanced metabolizing of rimsulfuron. An overall decrease in dry weight was observed in response to both herbicides at 16/22 °C (P < 0.0001). Rimsulfuron was effective against only one population when applied at 28/34 °C. A possible fitness cost associated with target site-resistant biotypes was observed under low temperature conditions, leading to effective control.

CONCLUSION: This regional-scale study highlights the challenges faced by growers, emphasizes the need for adapting management practices to the local climatic conditions and lays the groundwork for implementing location-specific weed management strategies in commercial fields. © 2024 The Author(s). Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.}, } @article {pmid38808993, year = {2024}, author = {Solomon, B}, title = {Bone marrow-derived microglia confer neuroprotection to a mouse model of amyotrophic lateral sclerosis.}, journal = {Neural regeneration research}, volume = {19}, number = {12}, pages = {2586-2587}, pmid = {38808993}, issn = {1673-5374}, } @article {pmid38807398, year = {2024}, author = {Kekenadze, M and Kvirkvelia, N and Beridze, M and Vashadze, S}, title = {SEROTONIN AND AMYOTROPHIC LATERAL SCLEROSIS.}, journal = {Georgian medical news}, volume = {}, number = {348}, pages = {87-90}, pmid = {38807398}, issn = {1512-0112}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/pathology ; *Serotonin/metabolism ; Middle Aged ; Female ; Male ; Adult ; Aged ; Aged, 80 and over ; Adolescent ; Motor Neurons/pathology ; Electromyography ; Magnetic Resonance Imaging ; }, abstract = {Selective degeneration of motoneurons is the pathological hallmark of amyotrophic lateral sclerosis (ALS). Does serotonin (5-HT) play a role in progression or development of disease is under the research. The topic of the present paper is pressing as there is no data available regarding the spread of amyotrophic lateral sclerosis. It is also noteworthy that previous studies have indicated that the pathogenesis of ALS is closely linked to 5-hydroxytryptamine (5-HT). The clinical research was conducted in Georgia. During the last five years, 60 patients from different parts of Georgia have been studied, searched, and examined by us. Including from Samegrolo, Kartli, Adjara, Abkhazia, Guria, Kakheti regions. The Georgian Neurologists Corps participated and helped us in finding patients. Brain MRI and electromyography were also performed. 60 patients with different forms of ALS participated in the study, including 34 (56.66%) men and 26 (43.33%) women. Their age ranges from 30 to 81 years. The study was conducted after obtaining the written consent of the patients, taking into account the ethical requirements for the study. We also compared the results of the serotonin level of patients with amyotrophic lateral sclerosis with a control group of 20 people (aged 18 to 50 years) who had no neurological disease in past medical history. Patients of the first group, with LMN damage, are observed with decreased amount of serotonin (61.3) %, compared to other pairs, followed by patients of the upper neuron and bulbar syndrome groups, the level of serotonin in the control group is quite high. Thus, the level of serotonin in the group of patients with bulbar events is higher than in the other groups. Low serotonin requires further investigation. According to our research, the longer the anamnesis of amyotrophic lateral sclerosis patients is, the lower the level of serotonin is observed. It should also be taken into account that a low level of serotonin may be due to the presence of depression, which requires additional research. We speculate that 5-HT could therefore be a potential therapeutic target for amyotrophic lateral sclerosis.}, } @article {pmid38807021, year = {2024}, author = {Rahimian, S and Najafi, H and Webber, CA and Jalali, H}, title = {Advances in Exosome-Based Therapies for the Repair of Peripheral Nerve Injuries.}, journal = {Neurochemical research}, volume = {49}, number = {8}, pages = {1905-1925}, pmid = {38807021}, issn = {1573-6903}, mesh = {*Exosomes/metabolism/transplantation ; Humans ; *Peripheral Nerve Injuries/therapy/metabolism ; Animals ; Nerve Regeneration/physiology ; }, abstract = {Peripheral nerve injuries (PNIs) are the term used to describe injuries that occur to the nerve fibers of the peripheral nervous system (PNS). Such injuries may be caused by trauma, infection, or aberrant immunological response. Although the peripheral nervous system has a limited capacity for self-repair, in cases of severe damage, this process is either interrupted entirely or is only partially completed. The evaluation of variables that promote the repair of peripheral nerves has consistently been a focal point. Exosomes are a subtype of extracellular vesicles that originate from cellular sources and possess abundant proteins, lipids, and nucleic acids, play a critical role in facilitating intercellular communication. Due to their modifiable composition, they possess exceptional capabilities as carriers for therapeutic compounds, including but not limited to mRNAs or microRNAs. Exosome-based therapies have gained significant attention in the treatment of several nervous system diseases due to their advantageous properties, such as low toxicity, high stability, and limited immune system activation. The objective of this review article is to provide an overview of exosome-based treatments that have been developed in recent years for a range of PNIs, including nerve trauma, diabetic neuropathy, amyotrophic lateral sclerosis (ALS), glaucoma, and Guillain-Barre syndrome (GBS). It was concluded that exosomes could provide favorable results in the improvement of peripheral PNIs by facilitating the transfer of regenerative factors. The development of bioengineered exosome therapy for PNIs should be given more attention to enhance the efficacy of exosome treatment for PNIs.}, } @article {pmid38806659, year = {2024}, author = {Xie, C and Chen, G and Li, M and Huang, P and Chen, Z and Lei, K and Li, D and Wang, Y and Cleetus, A and Mohamed, MA and Sonar, P and Feng, W and Ökten, Z and Ou, G}, title = {Neurons dispose of hyperactive kinesin into glial cells for clearance.}, journal = {The EMBO journal}, volume = {43}, number = {13}, pages = {2606-2635}, pmid = {38806659}, issn = {1460-2075}, support = {31991191//MOST | National Natural Science Foundation of China (NSFC)/ ; 32200612//MOST | National Natural Science Foundation of China (NSFC)/ ; 32071191//MOST | National Natural Science Foundation of China (NSFC)/ ; 31971160//MOST | National Natural Science Foundation of China (NSFC)/ ; 2019YFA0508401//MOST | National Key Research and Development Program of China (NKPs)/ ; XDB37020302//Strategic Priority Research Program of CAS/ ; }, mesh = {Animals ; *Caenorhabditis elegans/metabolism/genetics ; *Kinesins/metabolism/genetics ; *Caenorhabditis elegans Proteins/metabolism/genetics ; *Neuroglia/metabolism ; *Cilia/metabolism ; Neurons/metabolism ; Mutation ; Amyotrophic Lateral Sclerosis/metabolism/genetics/pathology ; }, abstract = {Microtubule-based kinesin motor proteins are crucial for intracellular transport, but their hyperactivation can be detrimental for cellular functions. This study investigated the impact of a constitutively active ciliary kinesin mutant, OSM-3CA, on sensory cilia in C. elegans. Surprisingly, we found that OSM-3CA was absent from cilia but underwent disposal through membrane abscission at the tips of aberrant neurites. Neighboring glial cells engulf and eliminate the released OSM-3CA, a process that depends on the engulfment receptor CED-1. Through genetic suppressor screens, we identified intragenic mutations in the OSM-3CA motor domain and mutations inhibiting the ciliary kinase DYF-5, both of which restored normal cilia in OSM-3CA-expressing animals. We showed that conformational changes in OSM-3CA prevent its entry into cilia, and OSM-3CA disposal requires its hyperactivity. Finally, we provide evidence that neurons also dispose of hyperactive kinesin-1 resulting from a clinic variant associated with amyotrophic lateral sclerosis, suggesting a widespread mechanism for regulating hyperactive kinesins.}, } @article {pmid38806131, year = {2024}, author = {Oliveira, D and Assoni, AF and Alves, LM and Sakugawa, A and Melo, US and Teles E Silva, AL and Sertie, AL and Caires, LC and Goulart, E and Ghirotto, B and Carvalho, VM and Ferrari, MR and Zatz, M}, title = {ALS-associated VRK1 R321C mutation causes proteostatic imbalance and mitochondrial defects in iPSC-derived motor neurons.}, journal = {Neurobiology of disease}, volume = {198}, number = {}, pages = {106540}, doi = {10.1016/j.nbd.2024.106540}, pmid = {38806131}, issn = {1095-953X}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology ; *Induced Pluripotent Stem Cells/metabolism ; *Motor Neurons/metabolism/pathology ; *Mitochondria/metabolism/genetics/pathology ; Male ; *Protein Serine-Threonine Kinases/genetics/metabolism ; Female ; Intracellular Signaling Peptides and Proteins/genetics/metabolism ; Proteostasis/genetics ; Middle Aged ; Mutation, Missense ; Adult ; }, abstract = {Vaccinia-related kinase 1 (VRK1) is a gene which has been implicated in the pathological process of a broad range of neurodevelopmental disorders as well as neuropathies, such as Amyotrophic Lateral Sclerosis (ALS). Here we report a family presenting ALS in an autosomal recessive mode of inheritance, segregating with a homozygous missense mutation located in VRK1 gene (p.R321C; Arg321Cys). Proteomic analyses from iPSC-derived motor neurons identified 720 proteins eligible for subsequent investigation, and our exploration of protein profiles revealed significant enrichments in pathways such as mTOR signaling, E2F, MYC targets, DNA repair response, cell proliferation and energetic metabolism. Functional studies further validated such alterations, showing that affected motor neurons presented decreased levels of global protein output, ER stress and downregulation of mTOR signaling. Mitochondrial alterations also pointed to decreased reserve capacity and increased non-mitochondrial oxygen consumption. Taken together, our results present the main pathological alterations associated with VRK1 mutation in ALS.}, } @article {pmid38805448, year = {2024}, author = {Fernandes, APM and Holanda, LJ and Lucena, LC and Silva, KERD and Lopes, ACSM and Borges, DT and Nagem, DAP and Valentim, RAM and Bougrain, L and Rodrigues Lindquist, AR}, title = {Electromyography as a tool to motion analysis for people with Amyotrophic Lateral Sclerosis: A protocol for a systematic review.}, journal = {PloS one}, volume = {19}, number = {5}, pages = {e0302479}, pmid = {38805448}, issn = {1932-6203}, mesh = {*Amyotrophic Lateral Sclerosis/physiopathology/diagnosis ; Humans ; *Electromyography/methods ; Systematic Reviews as Topic ; Muscle, Skeletal/physiopathology ; Movement/physiology ; Biomechanical Phenomena ; }, abstract = {Biomechanical analysis of human movement plays an essential role in understanding functional changes in people with Amyotrophic Lateral Sclerosis (ALS), providing information on muscle impairment. Studies suggest that surface electromyography (sEMG) may be able to quantify muscle activity, identify levels of fatigue, assess muscle strength, and monitor variation in limb movement. In this article, a systematic review protocol will analyze the psychometric properties of the sEMG regarding the clinical data on the skeletal muscles of people with ALS. This protocol uses the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodological tool. A specific field structure was defined to reach each phase. Nine scientific databases (PubMed, Web of Science, Embase, Elsevier, IEEE, Google Scholar, SciELO, PEDro, LILACS E CENTRAL) were searched. The framework developed will extract data (i.e. study information, sample information, sEMG information, intervention, and outcomes) from the selected studies using a rigorous approach. The data will be described quantitatively using frequency and trend analysis methods, and heterogeneity between the included studies will be assessed using the I2 test. The risk of bias will be summarized using the most recent prediction model risk of bias assessment tool. Be sure to include relevant statistics here, such as sample sizes, response rates, P values or Confidence Intervals. Be specific (by stating the value) rather than general (eg, "there were differences between the groups"). This protocol will map out the construction of a systematic review that will identify and synthesize the advances in movement analysis of people with ALS through sEMG, using data extracted from articles.}, } @article {pmid38805282, year = {2024}, author = {Bell, AM and Utting, C and Dickie, AC and Kucharczyk, MW and Quillet, R and Gutierrez-Mecinas, M and Razlan, ANB and Cooper, AH and Lan, Y and Hachisuka, J and Weir, GA and Bannister, K and Watanabe, M and Kania, A and Hoon, MA and Macaulay, IC and Denk, F and Todd, AJ}, title = {Deep sequencing of Phox2a nuclei reveals five classes of anterolateral system neurons.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {121}, number = {23}, pages = {e2314213121}, pmid = {38805282}, issn = {1091-6490}, support = {BB/S017178/1//UKRI | Biotechnology and Biological Sciences Research Council (BBSRC)/ ; 204820/Z/16/Z//Wellcome Trust (WT)/ ; MR/W004739/1//UKRI | Medical Research Council (MRC)/ ; BBS/E/T/000PR9816//UKRI | Biotechnology and Biological Sciences Research Council (BBSRC)/ ; MR/V033638/1//UKRI | Medical Research Council (MRC)/ ; /WT_/Wellcome Trust/United Kingdom ; SGL025\1079//Academy of Medical Sciences (The Academy of Medical Sciences)/ ; MR/W002426/1//UKRI | Medical Research Council (MRC)/ ; MR/T01072X/1//UKRI | Medical Research Council (MRC)/ ; ZIADE000721-22//HHS | NIH | National Institute of Dental and Craniofacial Research (NIDCR)/ ; MRF-160-0015-ELP-DENK-C0844//UKRI | MRC | Medical Research Foundation/ ; 219433/Z/19/Z//Wellcome Trust (WT)/ ; MR/T01072X/1/MRC_/Medical Research Council/United Kingdom ; MR/V033638/1/MRC_/Medical Research Council/United Kingdom ; BB/CCG1720/1//UKRI | Biotechnology and Biological Sciences Research Council (BBSRC)/ ; }, mesh = {Animals ; Mice ; *Homeodomain Proteins/genetics/metabolism ; Spinal Cord/cytology/metabolism ; Neurons/metabolism ; High-Throughput Nucleotide Sequencing ; Male ; Cell Nucleus/metabolism/genetics ; Transcription Factors/genetics/metabolism ; }, abstract = {The anterolateral system (ALS) is a major ascending pathway from the spinal cord that projects to multiple brain areas and underlies the perception of pain, itch, and skin temperature. Despite its importance, our understanding of this system has been hampered by the considerable functional and molecular diversity of its constituent cells. Here, we use fluorescence-activated cell sorting to isolate ALS neurons belonging to the Phox2a-lineage for single-nucleus RNA sequencing. We reveal five distinct clusters of ALS neurons (ALS1-5) and document their laminar distribution in the spinal cord using in situ hybridization. We identify three clusters of neurons located predominantly in laminae I-III of the dorsal horn (ALS1-3) and two clusters with cell bodies located in deeper laminae (ALS4 and ALS5). Our findings reveal the transcriptional logic that underlies ALS neuronal diversity in the adult mouse and uncover the molecular identity of two previously identified classes of projection neurons. We also show that these molecular signatures can be used to target groups of ALS neurons using retrograde viral tracing. Overall, our findings provide a valuable resource for studying somatosensory biology and targeting subclasses of ALS neurons.}, } @article {pmid38805054, year = {2024}, author = {Beswick, E and Christides, A and Symonds, A and Johnson, M and Fawcett, T and Newton, J and Lyle, D and Weaver, C and Chandran, S and Pal, S}, title = {Exploratory study to evaluate the acceptability of a wearable accelerometer to assess motor progression in motor neuron disease.}, journal = {Journal of neurology}, volume = {271}, number = {8}, pages = {5083-5101}, pmid = {38805054}, issn = {1432-1459}, mesh = {Humans ; Male ; Female ; Middle Aged ; *Motor Neuron Disease/physiopathology/diagnosis ; Aged ; *Wearable Electronic Devices ; *Accelerometry/instrumentation ; *Disease Progression ; Patient Acceptance of Health Care ; Surveys and Questionnaires/standards ; }, abstract = {Motor neuron disease (MND) is a rapidly progressive condition traditionally assessed using a questionnaire to evaluate physical function, the revised amyotrophic lateral sclerosis functional rating scale (ALSFRS-R). Its use can be associated with poor sensitivity in detecting subtle changes over time and there is an urgent need for more sensitive and specific outcome measures. The ActiGraph GT9X is a wearable device containing multiple sensors that can be used to provide metrics that represent physical activity. The primary aim of this study was to investigate the initial suitability and acceptability of limb-worn wearable devices to group of people with MND in Scotland. A secondary aim was to explore the preliminary associations between the accelerometer sensor data within the ActiGraph GT9X and established measures of physical function. 10 participants with MND completed a 12-week schedule of assessments including fortnightly study visits, both in-person and over videoconferencing software. Participants wore the device on their right wrist and right ankle for a series of movements, during a 6-min walking test and for a period of 24-h wear, including overnight. Participants also completed an ALSFRS-R and questionnaires on their experience with the devices. 80% of the participants found wearing these devices to be a positive experience and no one reported interference with daily living or added burden. However, 30% of the participants experienced technical issues with their devices. Data from the wearable devices correlated with established measures of physical function.}, } @article {pmid38805053, year = {2024}, author = {Bjelica, B and Bartels, MB and Hesebeck-Brinckmann, J and Petri, S}, title = {Non-motor symptoms in patients with amyotrophic lateral sclerosis: current state and future directions.}, journal = {Journal of neurology}, volume = {271}, number = {7}, pages = {3953-3977}, pmid = {38805053}, issn = {1432-1459}, mesh = {*Amyotrophic Lateral Sclerosis/physiopathology/diagnosis/complications ; Humans ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive degeneration of both upper and lower motor neurons. A defining histopathological feature in approximately 97% of all ALS cases is the accumulation of phosphorylated trans-activation response (TAR) DNA-binding protein 43 protein (pTDP-43) aggregates in the cytoplasm of neurons and glial cells within the central nervous system. Traditionally, it was believed that the accumulation of TDP-43 aggregates and subsequent neurodegeneration primarily occurs in motor neurons. However, contemporary evidence suggests that as the disease progresses, other systems and brain regions are also affected. Despite this, there has been a limited number of clinical studies assessing the non-motor symptoms in ALS patients. These studies often employ various outcome measures, resulting in a wide range of reported frequencies of non-motor symptoms in ALS patients. The importance of assessing the non-motor symptoms reflects in a fact that they have a significant impact on patients' quality of life, yet they frequently go underdiagnosed and unreported during clinical evaluations. This review aims to provide an up-to-date overview of the current knowledge concerning non-motor symptoms in ALS. Furthermore, we address their diagnosis and treatment in everyday clinical practice.}, } @article {pmid38802624, year = {2024}, author = {Riva, N and Domi, T and Pozzi, L and Lunetta, C and Schito, P and Spinelli, EG and Cabras, S and Matteoni, E and Consonni, M and Bella, ED and Agosta, F and Filippi, M and Calvo, A and Quattrini, A}, title = {Update on recent advances in amyotrophic lateral sclerosis.}, journal = {Journal of neurology}, volume = {271}, number = {7}, pages = {4693-4723}, pmid = {38802624}, issn = {1432-1459}, support = {IDEALS//Agenzia di Ricerca per la Sclerosi Laterale Amiotrofica/ ; Marazzina Project//Marazzina Foundation/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/therapy/genetics ; Humans ; Animals ; }, abstract = {In the last few years, our understanding of disease molecular mechanisms underpinning ALS has advanced greatly, allowing the first steps in translating into clinical practice novel research findings, including gene therapy approaches. Similarly, the recent advent of assistive technologies has greatly improved the possibility of a more personalized approach to supportive and symptomatic care, in the context of an increasingly complex multidisciplinary line of actions, which remains the cornerstone of ALS management. Against this rapidly growing background, here we provide an comprehensive update on the most recent studies that have contributed towards our understanding of ALS pathogenesis, the latest results from clinical trials as well as the future directions for improving the clinical management of ALS patients.}, } @article {pmid38802492, year = {2024}, author = {Watanabe, S and Amporndanai, K and Awais, R and Latham, C and Awais, M and O'Neill, PM and Yamanaka, K and Hasnain, SS}, title = {Ebselen analogues delay disease onset and its course in fALS by on-target SOD-1 engagement.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {12118}, pmid = {38802492}, issn = {2045-2322}, support = {WA1198//ALS Association/ ; }, mesh = {*Superoxide Dismutase-1/genetics/metabolism ; Animals ; *Organoselenium Compounds/pharmacology/therapeutic use ; *Amyotrophic Lateral Sclerosis/drug therapy/genetics/metabolism ; *Isoindoles/pharmacology ; Mice ; *Azoles/pharmacology ; Humans ; Mice, Transgenic ; Disease Models, Animal ; Neuroprotective Agents/pharmacology/therapeutic use ; }, abstract = {Amyotrophic lateral sclerosis (ALS) selectively affects motor neurons. SOD1 is the first causative gene to be identified for ALS and accounts for at least 20% of the familial (fALS) and up to 4% of sporadic (sALS) cases globally with some geographical variability. The destabilisation of the SOD1 dimer is a key driving force in fALS and sALS. Protein aggregation resulting from the destabilised SOD1 is arrested by the clinical drug ebselen and its analogues (MR6-8-2 and MR6-26-2) by redeeming the stability of the SOD1 dimer. The in vitro target engagement of these compounds is demonstrated using the bimolecular fluorescence complementation assay with protein-ligand binding directly visualised by co-crystallography in G93A SOD1. MR6-26-2 offers neuroprotection slowing disease onset of SOD1[G93A] mice by approximately 15 days. It also protected neuromuscular junction from muscle denervation in SOD1[G93A] mice clearly indicating functional improvement.}, } @article {pmid38802184, year = {2024}, author = {Vucic, S and de Carvalho, M and Bashford, J and Alix, JJP}, title = {Contribution of neurophysiology to the diagnosis and monitoring of ALS.}, journal = {International review of neurobiology}, volume = {176}, number = {}, pages = {87-118}, doi = {10.1016/bs.irn.2024.04.001}, pmid = {38802184}, issn = {2162-5514}, mesh = {*Amyotrophic Lateral Sclerosis/diagnosis/physiopathology ; Humans ; *Transcranial Magnetic Stimulation/methods ; *Electromyography/methods ; *Neurophysiology/methods ; Disease Progression ; Motor Cortex/physiopathology ; }, abstract = {This chapter describes the role of neurophysiological techniques in diagnosing and monitoring amyotrophic lateral sclerosis (ALS). Despite many advances, electromyography (EMG) remains a keystone investigation from which to build support for a diagnosis of ALS, demonstrating the pathophysiological processes of motor unit hyperexcitability, denervation and reinnervation. We consider development of the different diagnostic criteria and the role of EMG therein. While not formally recognised by established diagnostic criteria, we discuss the pioneering studies that have demonstrated the diagnostic potential of transcranial magnetic stimulation (TMS) of the motor cortex and highlight the growing evidence for TMS in the diagnostic process. Finally, accurately monitoring disease progression is crucial for the successful implementation of clinical trials. Neurophysiological measures of disease state have been incorporated into clinical trials for over 20 years and we review prominent techniques for assessing disease progression.}, } @article {pmid38802183, year = {2024}, author = {Moll, T and Harvey, C and Alhathli, E and Gornall, S and O'Brien, D and Cooper-Knock, J}, title = {Non-coding genome contribution to ALS.}, journal = {International review of neurobiology}, volume = {176}, number = {}, pages = {75-86}, doi = {10.1016/bs.irn.2024.04.002}, pmid = {38802183}, issn = {2162-5514}, mesh = {*Amyotrophic Lateral Sclerosis/genetics ; Humans ; Animals ; Genetic Predisposition to Disease/genetics ; }, abstract = {The majority of amyotrophic lateral sclerosis (ALS) is caused by a complex gene-environment interaction. Despite high estimates of heritability, the genetic basis of disease in the majority of ALS patients are unknown. This limits the development of targeted genetic therapies which require an understanding of patient-specific genetic drivers. There is good evidence that the majority of these missing genetic risk factors are likely to be found within the non-coding genome. However, a major challenge in the discovery of non-coding risk variants is determining which variants are functional in which specific CNS cell type. We summarise current discoveries of ALS-associated genetic drivers within the non-coding genome and we make the case that improved cell-specific annotation of genomic function is required to advance this field, particularly via single-cell epigenetic profiling and spatial transcriptomics. We highlight the example of TBK1 where an apparent paradox exists between pathogenic coding variants which cause loss of protein function, and protective non-coding variants which cause reduced gene expression; the paradox is resolved when it is understood that the non-coding variants are acting primarily via change in gene expression within microglia, and the effect of coding variants is most prominent in neurons. We propose that cell-specific functional annotation of ALS-associated genetic variants will accelerate discovery of the genetic architecture underpinning disease in the vast majority of patients.}, } @article {pmid38802182, year = {2024}, author = {Al-Chalabi, A and Andrews, J and Farhan, S}, title = {Recent advances in the genetics of familial and sporadic ALS.}, journal = {International review of neurobiology}, volume = {176}, number = {}, pages = {49-74}, doi = {10.1016/bs.irn.2024.04.007}, pmid = {38802182}, issn = {2162-5514}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics ; *Genetic Predisposition to Disease/genetics ; }, abstract = {ALS shows complex genetic inheritance patterns. In about 5% to 10% of cases, there is a family history of ALS or a related condition such as frontotemporal dementia in a first or second degree relative, and for about 80% of such people a pathogenic gene variant can be identified. Such variants are also seen in people with no family history because of factor influencing the expression of genes, such as age. Genetic susceptibility factors also contribute to risk, and the heritability of ALS is between 40% and 60%. The genetic variants influencing ALS risk include single base changes, repeat expansions, copy number variants, and others. Here we review what is known of the genetic landscape and architecture of ALS.}, } @article {pmid38802181, year = {2024}, author = {De Cock, L and Bercier, V and Van Den Bosch, L}, title = {New developments in pre-clinical models of ALS to guide translation.}, journal = {International review of neurobiology}, volume = {176}, number = {}, pages = {477-524}, doi = {10.1016/bs.irn.2024.04.008}, pmid = {38802181}, issn = {2162-5514}, mesh = {*Amyotrophic Lateral Sclerosis/genetics/physiopathology/therapy ; Animals ; *Disease Models, Animal ; Humans ; Translational Research, Biomedical/methods ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder in which selective death of motor neurons leads to muscle weakness and paralysis. Most research has focused on understanding and treating monogenic familial forms, most frequently caused by mutations in SOD1, FUS, TARDBP and C9orf72, although ALS is mostly sporadic and without a clear genetic cause. Rodent models have been developed to study monogenic ALS, but despite numerous pre-clinical studies and clinical trials, few disease-modifying therapies are available. ALS is a heterogeneous disease with complex underlying mechanisms where several genes and molecular pathways appear to play a role. One reason for the high failure rate of clinical translation from the current models could be oversimplification in pre-clinical studies. Here, we review advances in pre-clinical models to better capture the heterogeneous nature of ALS and discuss the value of novel model systems to guide translation and aid in the development of precision medicine.}, } @article {pmid38802180, year = {2024}, author = {Shelkovnikova, TA and Hautbergue, GM}, title = {RNP granules in ALS and neurodegeneration: From multifunctional membraneless organelles to therapeutic opportunities.}, journal = {International review of neurobiology}, volume = {176}, number = {}, pages = {455-479}, doi = {10.1016/bs.irn.2024.04.009}, pmid = {38802180}, issn = {2162-5514}, support = {MR/R024162/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism/pathology ; *Ribonucleoproteins/metabolism ; Animals ; *Cytoplasmic Granules/metabolism ; Neurodegenerative Diseases/metabolism ; Organelles/metabolism ; }, abstract = {Amyotrophic lateral sclerosis (ALS) and related neurodegenerative diseases are characterised by dysfunction of a host of RNA-binding proteins (RBPs) and a severely disrupted RNA metabolism. Recently, RBP-harbouring phase-separated complexes, ribonucleoprotein (RNP) granules, have come into the limelight as "crucibles" of neuronal pathology in ALS. RNP granules are indispensable for the multitude of regulatory processes underlying cellular RNA metabolism and serve as critical organisers of cellular biochemistry. Neurons, highly specialised cells, heavily rely on RNP granules for efficient trafficking, signalling and stress responses. Multiple RNP granule components, primarily RBPs such as TDP-43 and FUS, are affected by ALS mutations. However, even in the absence of mutations, RBP proteinopathies represent pathophysiological hallmarks of ALS. Given the high local concentrations of RBPs and RNAs, their weakened or enhanced interactions within RNP granules disrupt their homeostasis. Thus, the physiological process of phase separation and RNP granule formation, vital for maintaining the high-functioning state of neuronal cells, becomes their Achilles heel. Here, we will review the recent literature on the causes and consequences of abnormal RNP granule functioning in ALS and related disorders. In particular, we will summarise the evidence for the network-level dysfunction of RNP granules in these conditions and discuss considerations for therapeutic interventions to target RBPs, RNP granules and their network as a whole.}, } @article {pmid38802179, year = {2024}, author = {Pandya, VA and Patani, R}, title = {The role of glial cells in amyotrophic lateral sclerosis.}, journal = {International review of neurobiology}, volume = {176}, number = {}, pages = {381-450}, doi = {10.1016/bs.irn.2024.04.005}, pmid = {38802179}, issn = {2162-5514}, mesh = {*Amyotrophic Lateral Sclerosis/pathology/physiopathology/therapy ; Humans ; *Neuroglia/physiology ; Animals ; }, abstract = {Amyotrophic lateral sclerosis (ALS) has traditionally been considered a neuron-centric disease. This view is now outdated, with increasing recognition of cell autonomous and non-cell autonomous contributions of central and peripheral nervous system glia to ALS pathomechanisms. With glial research rapidly accelerating, we comprehensively interrogate the roles of astrocytes, microglia, oligodendrocytes, ependymal cells, Schwann cells and satellite glia in nervous system physiology and ALS-associated pathology. Moreover, we highlight the inter-glial, glial-neuronal and inter-system polylogue which constitutes the healthy nervous system and destabilises in disease. We also propose classification based on function for complex glial reactive phenotypes and discuss the pre-requisite for integrative modelling to advance translation. Given the paucity of life-enhancing therapies currently available for ALS patients, we discuss the promising potential of harnessing glia in driving ALS therapeutic discovery.}, } @article {pmid38802177, year = {2024}, author = {Lee, J and Pye, N and Ellis, L and Vos, K and Mortiboys, H}, title = {Evidence of mitochondrial dysfunction in ALS and methods for measuring in model systems.}, journal = {International review of neurobiology}, volume = {176}, number = {}, pages = {269-325}, doi = {10.1016/bs.irn.2024.04.006}, pmid = {38802177}, issn = {2162-5514}, mesh = {*Amyotrophic Lateral Sclerosis/metabolism/pathology ; Humans ; *Mitochondria/metabolism ; Animals ; Reactive Oxygen Species/metabolism ; Disease Models, Animal ; Oxidative Stress/physiology ; }, abstract = {Metabolic dysfunction is a hallmark of multiple amyotrophic lateral sclerosis (ALS) models with a majority of ALS patients exhibiting hypermetabolism. The central sites of metabolism in the cell are mitochondria, capable of utilising a multitude of cellular substrates in an array of ATP-generating reactions. With reactive oxygen species (ROS) production occurring during some of these reactions, mitochondria can contribute considerably to oxidative stress. Mitochondria are also very dynamic organelles, interacting with other organelles, undergoing fusion/fission in response to changing metabolic states and being turned over by the cell regularly. Disruptions to many of these mitochondrial functions and processes have been reported in ALS models, largely indicating compromised mitochondrial function, increased ROS production by mitochondria, disrupted interactions with the endoplasmic reticulum and reduced turnover. This chapter summarises methods routinely used to assess mitochondria in ALS models and the alterations that have been reported in these models.}, } @article {pmid38802176, year = {2024}, author = {Castelli, L and Vasta, R and Allen, SP and Waller, R and Chiò, A and Traynor, BJ and Kirby, J}, title = {From use of omics to systems biology: Identifying therapeutic targets for amyotrophic lateral sclerosis.}, journal = {International review of neurobiology}, volume = {176}, number = {}, pages = {209-268}, doi = {10.1016/bs.irn.2024.02.001}, pmid = {38802176}, issn = {2162-5514}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/metabolism/drug therapy/therapy ; *Systems Biology/methods ; *Genomics/methods ; Proteomics/methods ; Animals ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a heterogeneous progressive neurodegenerative disorder with available treatments such as riluzole and edaravone extending survival by an average of 3-6 months. The lack of highly effective, widely available therapies reflects the complexity of ALS. Omics technologies, including genomics, transcriptomic and proteomics have contributed to the identification of biological pathways dysregulated and targeted by therapeutic strategies in preclinical and clinical trials. Integrating clinical, environmental and neuroimaging information with omics data and applying a systems biology approach can further improve our understanding of the disease with the potential to stratify patients and provide more personalised medicine. This chapter will review the omics technologies that contribute to a systems biology approach and how these components have assisted in identifying therapeutic targets. Current strategies, including the use of genetic screening and biosampling in clinical trials, as well as the future application of additional technological advances, will also be discussed.}, } @article {pmid38802175, year = {2024}, author = {Malaspina, A}, title = {Use of biomarkers in clinical trials and future developments that will help identify novel biomarkers.}, journal = {International review of neurobiology}, volume = {176}, number = {}, pages = {171-207}, doi = {10.1016/bs.irn.2024.04.010}, pmid = {38802175}, issn = {2162-5514}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy/diagnosis/genetics/metabolism/drug therapy ; *Biomarkers ; *Clinical Trials as Topic/methods ; }, abstract = {Engineering new solutions for therapeutic benefit in Amyotrophic Lateral Sclerosis (ALS) has proved a difficult task to accomplish. This is largely the reflection of complexities at multiple levels, that require solutions to improve cost-effectiveness and outcomes. The main obstacle related to the condition's clinical heterogeneity, chiefly the broad difference in survival observed among ALS patients, imposes large populations studies and long follow-up to evaluate any efficacy. The emerging solution is composite clinical and biological parameters enabling prognostic stratification into homogeneous phenotypes for more affordable studies. From a therapeutic development perspective, the choice of a medicinal product requires the availability of treatment-specific biomarkers of target engagement to identify off-target effects based on the compound's putative modality of action. More importantly, there are no established biomarkers of treatment response that can complement clinical outcome measures and support futility and end of treatment analyses of efficacy. Ultimately the onus rests on the development of biomarkers encompassing the unmet needs of clinical trial design, from inclusion to efficacy. These readouts of the pathological process may be used in combination with clinical and paraclinical outcome measured, significantly reducing the time and financial burden of clinical studies. Progress towards a biomarker-driven clinical trial design in ALS has been possible thanks to the accurate detection of neurofilaments and of other immunological mediators in biological fluids with the disease progression, a step change enabling the testing of novel therapeutic agents in a new clinical trial setting. However, further progress remains to be made to find treatment specific target engagement biomarkers along with readouts of treatment response that can be reliably applied to all emerging therapies and clinical studies. Here we will cover the basic notions of biomarker development in ALS clinical trials, the most crucial unanswered questions and the unmet needs in the ALS biomarkers space.}, } @article {pmid38802174, year = {2024}, author = {Hobson, E and McDermott, C}, title = {Advances in symptom management and in monitoring disease progression in motor neuron disease.}, journal = {International review of neurobiology}, volume = {176}, number = {}, pages = {119-169}, doi = {10.1016/bs.irn.2024.04.004}, pmid = {38802174}, issn = {2162-5514}, mesh = {Humans ; *Motor Neuron Disease/therapy/physiopathology ; *Disease Progression ; Disease Management ; Quality of Life ; }, abstract = {The aim of supportive management of motor neuron disease is to improve survival, promote good quality of life and patient independence and autonomy whilst preparing for future progression and the end of life. Multidisciplinary specialist care aims to address the multifaceted and interacting biopsychosocial problems associated with motor neuron disease that leads to proven benefits in both survival and quality of life. This chapter will explore principles, structure and details of treatment options, and make recommendations for practice and for future research.}, } @article {pmid38802173, year = {2024}, author = {Van Es, MA}, title = {Amyotrophic lateral sclerosis; clinical features, differential diagnosis and pathology.}, journal = {International review of neurobiology}, volume = {176}, number = {}, pages = {1-47}, doi = {10.1016/bs.irn.2024.04.011}, pmid = {38802173}, issn = {2162-5514}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/genetics/pathology/physiopathology ; Diagnosis, Differential ; Frontotemporal Dementia/diagnosis/genetics/physiopathology/pathology ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a late-onset syndrome characterized by the progressive degeneration of both upper motor neurons (UMN) and lower motor neurons (LMN). ALS forms a clinical continuum with frontotemporal dementia (FTD), in which there are progressive language deficits or behavioral changes. The genetics and pathology underlying both ALS and FTD overlap as well, with cytoplasmatic misvocalization of TDP-43 as the hallmark. ALS is diagnosed by exclusion. Over the years several diagnostic criteria have been proposed, which in essence all require a history of slowly progressive motor symptoms, with UMN and LMN signs on neurological examination, clear spread of symptoms through the body, the exclusion of other disorder that cause similar symptoms and an EMG that it is compatible with LMN loss. ALS is heterogeneous disorder that may present in multitude ways, which makes the diagnosis challenging. Therefore, a systematic approach in the diagnostic process is required in line with the most common presentations. Subsequently, assessing whether there are cognitive and/or behavioral changes within the spectrum of FTD and lastly determining the cause is genetic. This chapter, an outline on how to navigate this 3 step process.}, } @article {pmid38799643, year = {2024}, author = {Xu, S and Ma, Q and Shen, J and Li, N and Sun, S and Wang, N and Chen, Y and Dong, C and Tam, KY and Prehn, JHM and Wang, H and Ying, Z}, title = {ALS-linked C9orf72 dipeptide repeats inhibit starvation-induced autophagy through modulating BCL2-BECN1 interaction.}, journal = {Acta pharmaceutica Sinica. B}, volume = {14}, number = {5}, pages = {2026-2038}, pmid = {38799643}, issn = {2211-3835}, abstract = {Growing evidences indicate that dysfunction of autophagy contributes to the disease pathogenesis of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), two neurodegenerative disorders. The GGGGCC·GGCCCC repeat RNA expansion in chromosome 9 open reading frame 72 (C9orf72) is the most genetic cause of both ALS and FTD. According to the previous studies, GGGGCC·GGCCCC repeat undergoes the unconventional repeat-associated non-ATG translation, which produces dipeptide repeat (DPR) proteins. Although there is a growing understanding that C9orf72 DPRs have a strong ability to harm neurons and induce C9orf72-linked ALS/FTD, whether these DPRs can affect autophagy remains unclear. In the present study, we find that poly-GR and poly-PR, two arginine-containing DPRs which display the most cytotoxic properties according to the previous studies, strongly inhibit starvation-induced autophagy. Moreover, our data indicate that arginine-rich DPRs enhance the interaction between BCL2 and BECN1/Beclin 1 by inhibiting BCL2 phosphorylation, therefore they can impair autophagic clearance of neurodegenerative disease-associated protein aggregates under starvation condition in cells. Importantly, our study not only highlights the role of C9orf72 DPR in autophagy dysfunction, but also provides novel insight that pharmacological intervention of autophagy using SW063058, a small molecule compound that can disrupt the interaction between BECN1 and BCL2, may reduce C9orf72 DPR-induced neurotoxicity.}, } @article {pmid38798695, year = {2024}, author = {Conforti, FL and Renton, AE and Houlden, H}, title = {Editorial: Multifaceted genes in amyotrophic lateral sclerosis-frontotemporal dementia volume II.}, journal = {Frontiers in genetics}, volume = {15}, number = {}, pages = {1420029}, doi = {10.3389/fgene.2024.1420029}, pmid = {38798695}, issn = {1664-8021}, } @article {pmid38798645, year = {2024}, author = {Landry, C and Costanzo, J and Mitne-Neto, M and Zatz, M and Schaffer, A and Hatzoglou, M and Muotri, A and Miranda, HC}, title = {Mitochondrial dysfunction heightens the integrated stress response to drive ALS pathogenesis.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2024.05.13.594000}, pmid = {38798645}, issn = {2692-8205}, support = {R01 NS121374/NS/NINDS NIH HHS/United States ; R61 NS133212/NS/NINDS NIH HHS/United States ; }, abstract = {Vesicle-associated membrane protein-associated protein-B (VAPB) is an ER membrane bound protein. VAPB P56S causes a dominant, familial form of amyotrophic lateral sclerosis (ALS), however, the mechanism through which this mutation causes motor neuron (MN) disease remains unknown. Using inducible wild type (WT) and VAPB P56S expressing iPSC-derived MNs we show that VAPB P56S, but not WT, protein decreased neuronal firing and mitochondrial-ER contact (MERC) with an associated age-dependent decrease in mitochondrial membrane potential (MMP); all typical characteristics of MN-disease. We further show that VAPB P56S expressing iPSC-derived MNs have enhanced age-dependent sensitivity to ER stress. We identified elevated expression of the master regulator of the Integrated Stress Response (ISR) marker ATF4 and decreased protein synthesis in the VAPB P56S iPSC-derived MNs. Chemical inhibition of ISR with the compound, ISRIB, rescued all MN disease phenotype in VAPB P56S MNs. Thus, our results not only support ISR inhibition as a potential therapeutic target for ALS patients, but also provides evidence to pathogenesis.}, } @article {pmid38798341, year = {2024}, author = {Provasek, VE and Bacolla, A and Rangaswamy, S and Mitra, J and Kodavati, M and Yusuf, IO and Malojirao, VH and Vasquez, V and Britz, GW and Li, GM and Xu, Z and Mitra, S and Garruto, RM and Tainer, JA and Hegde, ML}, title = {RNA/DNA Binding Protein TDP43 Regulates DNA Mismatch Repair Genes with Implications for Genome Stability.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {38798341}, issn = {2692-8205}, support = {R35 CA220430/CA/NCI NIH HHS/United States ; R01 NS094535/NS/NINDS NIH HHS/United States ; P01 CA092584/CA/NCI NIH HHS/United States ; R01 NS088645/NS/NINDS NIH HHS/United States ; R03 AG064266/AG/NIA NIH HHS/United States ; RF1 NS112719/NS/NINDS NIH HHS/United States ; }, abstract = {TAR DNA-binding protein 43 (TDP43) is increasingly recognized for its involvement in neurodegenerative diseases, particularly amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). TDP43 proteinopathy, characterized by dysregulated nuclear export and cytoplasmic aggregation, is present in most ALS/FTD cases and is associated with a loss of nuclear function and genomic instability in neurons. Building on prior evidence linking TDP43 pathology to DNA double-strand breaks (DSBs), this study identifies a novel regulatory role for TDP43 in the DNA mismatch repair (MMR) pathway. We demonstrate that depletion or overexpression of TDP43 affects the expression of key MMR genes, including MLH1, MSH6, MSH2, MSH3, and PMS2. Specifically, TDP43 modulates the expression of MLH1 and MSH6 proteins through alternative splicing and transcript stability. These findings are validated in ALS mice models, patient-derived neural progenitor cells and autopsied brain tissues from ALS patients. Furthermore, MMR depletion showed a partial rescue of TDP43-induced DNA damage in neuronal cells. Bioinformatics analysis of TCGA cancer database reveals significant correlations between TDP43 and MMR gene expressions and mutational burden across various cancer subtypes. These results collectively establish TDP43 as a critical regulator of the MMR pathway, with broad implications for understanding the genomic instability underlying neurodegenerative and neoplastic diseases.}, } @article {pmid38796984, year = {2024}, author = {Jiang, L and Tracey, TJ and Gill, MK and Howe, SL and Power, DT and Bharti, V and McCombe, PA and Henderson, RD and Steyn, FJ and Ngo, ST}, title = {Generation of human induced pluripotent stem cell lines from sporadic, sporadic frontotemporal dementia, familial SOD1, and familial C9orf72 amyotrophic lateral sclerosis (ALS) patients.}, journal = {Stem cell research}, volume = {78}, number = {}, pages = {103447}, doi = {10.1016/j.scr.2024.103447}, pmid = {38796984}, issn = {1876-7753}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/pathology/metabolism ; *Induced Pluripotent Stem Cells/metabolism ; *Frontotemporal Dementia/genetics/pathology/metabolism ; *C9orf72 Protein/genetics/metabolism ; *Superoxide Dismutase-1/genetics/metabolism ; Female ; Male ; Cell Line ; Middle Aged ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease. Clinical heterogeneity and complex genetics pose challenges to understanding disease mechanisms and producing effective cures. To model clinical heterogeneity, we generated human induced pluripotent stem cells (iPSCs) from two sporadic ALS patients (sporadic ALS and sporadic ALS with frontotemporal dementia), two familial ALS patients (familial SOD1 mutation positive and familial C9orf72 repeat expansion positive), and four age- and sex-matched healthy controls. These iPSCs can be used to generate 2D and 3D in vitro models of ALS to investigate mechanisms of disease and screen for therapeutics.}, } @article {pmid38796647, year = {2024}, author = {Chong, NF and Van de Wouw, AP and Idnurm, A}, title = {The ilv2 gene, encoding acetolactate synthase for branched chain amino acid biosynthesis, is required for plant pathogenicity by Leptosphaeria maculans.}, journal = {Molecular biology reports}, volume = {51}, number = {1}, pages = {682}, pmid = {38796647}, issn = {1573-4978}, mesh = {*Acetolactate Synthase/genetics/metabolism ; *Plant Diseases/microbiology ; *Herbicides/pharmacology ; *Amino Acids, Branched-Chain/biosynthesis/metabolism ; *Leptosphaeria/genetics/pathogenicity ; Mutation/genetics ; Fungal Proteins/genetics/metabolism ; Gene Editing/methods ; Plant Leaves/microbiology ; CRISPR-Cas Systems/genetics ; Brassica/microbiology ; Ascomycota/pathogenicity/genetics ; }, abstract = {BACKGROUND: Control of blackleg disease of canola caused by the fungus Leptosphaeria maculans relies on strategies such as the inhibition of growth with fungicides. However, other chemicals are used during canola cultivation, including fertilizers and herbicides. There is widespread use of herbicides that target the acetolactate synthase (ALS) enzyme involved in branched chain amino acid synthesis and low levels of these amino acids within leaves of Brassica species. In L. maculans the ilv2 gene encodes ALS and thus ALS-inhibiting herbicides may inadvertently impact the fungus.

METHODS AND RESULTS: Here, the impact of a commercial herbicide targeting ALS and mutation of the homologous ilv2 gene in L. maculans was explored. Exposure to herbicide had limited impact on growth in vitro but reduced lesion sizes in plant disease experiments. Furthermore, the mutation of the ilv2 gene via CRISPR-Cas9 gene editing rendered the fungus non-pathogenic.

CONCLUSION: Herbicide applications can influence disease outcome, but likely to a minor extent.}, } @article {pmid38795957, year = {2024}, author = {Bhushan, NL and Romano, CD and Gras-Najjar, J and Reno, J and Rockwood, N and Quattrone, W and Adams, ET and Kelly, B and McLeod, L and Bhavnani, SP and Bocell, FD and Campbell, M and Kontson, K and Reasner, D and Zhang, C and Retzky, S}, title = {Remote-Use Applications of the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised Clinical Outcome Assessment Tool: A Scoping Review.}, journal = {Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research}, volume = {27}, number = {10}, pages = {1454-1465}, doi = {10.1016/j.jval.2024.05.005}, pmid = {38795957}, issn = {1524-4733}, support = {75F40120A00017/FD/FDA HHS/United States ; }, mesh = {*Amyotrophic Lateral Sclerosis/therapy/physiopathology ; Humans ; *Outcome Assessment, Health Care/methods ; Telemedicine ; Severity of Illness Index ; Videoconferencing ; }, abstract = {OBJECTIVES: In 2021, the US Congress passed the Accelerating Access to Critical Therapies for Amyotrophic Lateral Sclerosis Act. The law encourages development of "tools, methods, and processes" to improve clinical trial efficiency for neurodegenerative diseases. The Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) is an outcome measure administered during in-person clinic visits and used to support investigational studies for persons living with amyotrophic lateral sclerosis. Availability of a standardized, remote-use version of the ALSFRS-R may promote more inclusive, decentralized clinical trials. A scoping literature review was conducted to identify existing remote-use ALSFRS-R tools, synthesize feasibility and comparability of administration modes, and summarize barriers and facilitators to inform development of a standardized remote-use ALSFRS-R tool.

METHODS: Included studies reported comparisons between remote and in-person, clinician-reported, ALSFRS-R administration and were published in English (2002-2022). References were identified by searching peer-reviewed and gray literature. Twelve studies met the inclusion criteria and were analyzed to compare findings within and across modes of administration.

RESULTS: Remote modes of ALSFRS-R administration were categorized into 4 nonmutually exclusive categories: telephone (n = 6), videoconferencing (n = 3), computer or online platforms (n = 3), mobile applications and wearables (n = 2), and 1 unspecified telemedicine modality (n = 1). Studies comparing in-person to telephone or videoconferencing administration reported high ALSFRS-R rating correlations and nonsignificant between-mode differences.

CONCLUSIONS: There is insufficient information in the ALSFRS-R literature to support remote clinician administration for collecting high quality data. Future research should engage persons living with amyotrophic lateral sclerosis, care partners, and providers to develop a standardized remote-use ALSFRS-R version.}, } @article {pmid38795892, year = {2024}, author = {Ridho, MR and Lubis, MAR and Nawawi, DS and Fatriasari, W}, title = {Optimization of areca leaf sheath nanolignin synthesis by a mechanical method for in situ modification of ultra-low molar ratio urea-formaldehyde adhesives.}, journal = {International journal of biological macromolecules}, volume = {271}, number = {Pt 1}, pages = {132614}, doi = {10.1016/j.ijbiomac.2024.132614}, pmid = {38795892}, issn = {1879-0003}, mesh = {*Formaldehyde/chemistry ; *Adhesives/chemistry ; *Urea/chemistry ; Plant Leaves/chemistry ; Particle Size ; Lignin/chemistry ; }, abstract = {This study addresses the optimization of the nanolignin preparation method from the areca leaf sheath (ALS) by a mechanical process using a high shear homogenizer at 13,000-16,000 rpm for 1-4 h and its application in enhancing the performance of ultralow molar ratio urea-formaldehyde (UF) adhesive. Response surface methodology (RSM) with a central composite design (CCD) model was used to determine the optimum nanolignin preparation method. The mathematical model obtained was quadratic for the particle size response and linear for the zeta potential response. Under the optimum conditions, a speed of 16,000 rpm for 4 h resulted in a particle size of 227.7 nm and a zeta potential of -18.57 mV with a high desirability value of 0.970. FE-SEM revealed that the characteristic changes of lignin to nanolignin occur from an irregular or nonuniform shape to an oval shape with uniform particles. Nanolignin was introduced during the addition reaction of UF resin synthesis. UF modified with nanolignin (UF-NL) was analyzed for its adhesive characteristics, functional groups, crystallinity, and thermomechanical properties. The UF-NL adhesive had a slightly greater solid content (73.23 %) than the UF adhesive, a gelation time of 4.10 min, and a viscosity of 1066 mPa[.]s. The UF-NL adhesive had similar functional groups as the UF adhesive, with a lower crystallinity of 59.73 %. Compared with the control plywood which has a tensile shear strength value of 0.79 MPa, the plywood bonded with UF-NL had a greater tensile shear strength of 1.07 MPa, with a lower formaldehyde emission of 0.065 mg/L.}, } @article {pmid38795640, year = {2024}, author = {Li, Z and Zhang, Y and Ji, M and Wu, C and Zhang, Y and Ji, S}, title = {Targeting ferroptosis in neuroimmune and neurodegenerative disorders for the development of novel therapeutics.}, journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie}, volume = {176}, number = {}, pages = {116777}, doi = {10.1016/j.biopha.2024.116777}, pmid = {38795640}, issn = {1950-6007}, mesh = {*Ferroptosis/drug effects/physiology ; Humans ; *Neurodegenerative Diseases/drug therapy/immunology/metabolism/pathology ; Animals ; Neuroimmunomodulation ; }, abstract = {Neuroimmune and neurodegenerative ailments impose a substantial societal burden. Neuroimmune disorders involve the intricate regulatory interactions between the immune system and the central nervous system. Prominent examples of neuroimmune disorders encompass multiple sclerosis and neuromyelitis optica. Neurodegenerative diseases result from neuronal degeneration or demyelination in the brain or spinal cord, such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. The precise underlying pathogenesis of these conditions remains incompletely understood. Ferroptosis, a programmed form of cell death characterised by lipid peroxidation and iron overload, plays a pivotal role in neuroimmune and neurodegenerative diseases. In this review, we provide a detailed overview of ferroptosis, its mechanisms, pathways, and regulation during the progression of neuroimmune and neurodegenerative diseases. Furthermore, we summarise the impact of ferroptosis on neuroimmune-related cells (T cells, B cells, neutrophils, and macrophages) and neural cells (glial cells and neurons). Finally, we explore the potential therapeutic implications of ferroptosis inhibitors in diverse neuroimmune and neurodegenerative diseases.}, } @article {pmid38795036, year = {2024}, author = {Chen, X and Cao, Z and Wang, Y}, title = {Amyotrophic Lateral Sclerosis-Associated Mutants of SOD1 Perturb mRNA Splicing through Aberrant Interactions with SRSF2.}, journal = {Analytical chemistry}, volume = {96}, number = {23}, pages = {9713-9720}, pmid = {38795036}, issn = {1520-6882}, support = {R35 ES031707/ES/NIEHS NIH HHS/United States ; }, mesh = {*Serine-Arginine Splicing Factors/metabolism/genetics ; Humans ; *Amyotrophic Lateral Sclerosis/genetics/metabolism ; *Superoxide Dismutase-1/metabolism/genetics/chemistry ; *RNA Splicing ; *Mutation ; RNA, Messenger/genetics/metabolism ; HEK293 Cells ; Biotinylation ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder that results in the degeneration of neurons in the brain and spinal cord. Although a substantial number of studies have been conducted, much remains to be learned about the cellular mechanisms underlying ALS. In this study, we employed an engineered ascorbate peroxidase (APEX)-based proximity biotinylation, together with affinity pull-down of the ensuing biotinylated peptides, to investigate the proximity proteomes of human SOD1 and its two ALS-linked mutants, G85R and G93A. We were able to identify 25 common biotinylated peptides with preferential enrichment in the proximity proteomes of SOD1[G85R] and SOD1[G93A] over wild-type SOD1. Our coimmunoprecipitation followed by Western blot analyses revealed that one of these proteins, SRSF2, binds more strongly with the two SOD1 mutants than its wild-type counterpart. We also observed aberrant splicing of mRNAs in cells with ectopic expression of the two SOD1 mutants relative to cells expressing the wild-type protein. In addition, the aberrations in splicing elicited by the SOD1 variants were markedly attenuated upon knockdown of SRSF2. Collectively, we uncovered that ALS-liked SOD1[G85R] and SOD1[G93A] mutants interact more strongly with SRSF2, where the aberrant interactions perturbed mRNA splicing. Thus, our work offered novel mechanistic insights into the contributions of the ALS-linked SOD1 mutants to disease etiology.}, } @article {pmid38791160, year = {2024}, author = {Bocheva, G and Bakalov, D and Iliev, P and Tafradjiiska-Hadjiolova, R}, title = {The Vital Role of Melatonin and Its Metabolites in the Neuroprotection and Retardation of Brain Aging.}, journal = {International journal of molecular sciences}, volume = {25}, number = {10}, pages = {}, pmid = {38791160}, issn = {1422-0067}, mesh = {*Melatonin/metabolism/pharmacology/therapeutic use ; Humans ; *Brain/metabolism/drug effects ; *Aging/metabolism/drug effects ; Animals ; *Neurodegenerative Diseases/metabolism/drug therapy ; *Neuroprotection/drug effects ; *Neuroprotective Agents/therapeutic use/pharmacology ; Oxidative Stress/drug effects ; Kynuramine/metabolism/analogs & derivatives ; }, abstract = {While primarily produced in the pineal gland, melatonin's influence goes beyond its well-known role in regulating sleep, nighttime metabolism, and circadian rhythms, in the field of chronobiology. A plethora of new data demonstrates melatonin to be a very powerful molecule, being a potent ROS/RNS scavenger with anti-inflammatory, immunoregulatory, and oncostatic properties. Melatonin and its metabolites exert multiple beneficial effects in cutaneous and systemic aging. This review is focused on the neuroprotective role of melatonin during aging. Melatonin has an anti-aging capacity, retarding the rate of healthy brain aging and the development of age-related neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, Huntington's disease, multiple sclerosis, amyotrophic lateral sclerosis, etc. Melatonin, as well as its metabolites, N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK) and N1-acetyl-5-methoxykynuramine (AMK), can reduce oxidative brain damage by shielding mitochondria from dysfunction during the aging process. Melatonin could also be implicated in the treatment of neurodegenerative conditions, by modifying their characteristic low-grade neuroinflammation. It can either prevent the initiation of inflammatory responses or attenuate the ongoing inflammation. Drawing on the current knowledge, this review discusses the potential benefits of melatonin supplementation in preventing and managing cognitive impairment and neurodegenerative diseases.}, } @article {pmid38791099, year = {2024}, author = {Moțățăianu, A and Mănescu, IB and Șerban, G and Bărcuțean, L and Ion, V and Bălașa, R and Andone, S}, title = {Exploring the Role of Metabolic Hormones in Amyotrophic Lateral Sclerosis.}, journal = {International journal of molecular sciences}, volume = {25}, number = {10}, pages = {}, pmid = {38791099}, issn = {1422-0067}, support = {PN-III-P1-1.1-TE-2021-0960//Ministry of Research, Innovation and Digitization, CNCS - UEFISCDI, Romania/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism/blood ; Male ; Female ; Middle Aged ; Aged ; *Islet Amyloid Polypeptide/metabolism/blood ; Cross-Sectional Studies ; *Biomarkers/blood ; *Insulin/metabolism/blood ; Disease Progression ; Leptin/blood/metabolism ; Glucagon-Like Peptide 1/metabolism/blood ; C-Peptide/blood/metabolism ; Ghrelin/metabolism/blood ; Glucagon/blood/metabolism ; Adult ; Hormones/metabolism/blood ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by progressive loss of motor neurons. Emerging evidence suggests a potential link between metabolic dysregulation and ALS pathogenesis. This study aimed to investigate the relationship between metabolic hormones and disease progression in ALS patients. A cross-sectional study was conducted involving 44 ALS patients recruited from a tertiary care center. Serum levels of insulin, total amylin, C-peptide, active ghrelin, GIP (gastric inhibitory peptide), GLP-1 active (glucagon-like peptide-1), glucagon, PYY (peptide YY), PP (pancreatic polypeptide), leptin, interleukin-6, MCP-1 (monocyte chemoattractant protein-1), and TNFα (tumor necrosis factor alpha) were measured, and correlations with ALSFRS-R, evolution scores, and biomarkers were analyzed using Spearman correlation coefficients. Subgroup analyses based on ALS subtypes, progression pattern of disease, and disease progression rate patterns were performed. Significant correlations were observed between metabolic hormones and ALS evolution scores. Insulin and amylin exhibited strong correlations with disease progression and clinical functional outcomes, with insulin showing particularly robust associations. Other hormones such as C-peptide, leptin, and GLP-1 also showed correlations with ALS progression and functional status. Subgroup analyses revealed differences in hormone levels based on sex and disease evolution patterns, with male patients showing higher amylin and glucagon levels. ALS patients with slower disease progression exhibited elevated levels of amylin and insulin. Our findings suggest a potential role for metabolic hormones in modulating ALS progression and functional outcomes. Further research is needed to elucidate the underlying mechanisms and explore the therapeutic implications of targeting metabolic pathways in ALS management.}, } @article {pmid38790984, year = {2024}, author = {Zhdanov, DD and Gladilina, YA and Blinova, VG and Abramova, AA and Shishparenok, AN and Eliseeva, DD}, title = {Induction of FoxP3 Pre-mRNA Alternative Splicing to Enhance the Suppressive Activity of Regulatory T Cells from Amyotrophic Lateral Sclerosis Patients.}, journal = {Biomedicines}, volume = {12}, number = {5}, pages = {}, pmid = {38790984}, issn = {2227-9059}, support = {23-24-00326//Russian Science Foundation/ ; }, abstract = {Forkhead box protein 3 (FoxP3) is a key transcription factor responsible for the development, maturation, and function of regulatory T cells (Tregs). The FoxP3 pre-mRNA is subject to alternative splicing, resulting in the translation of multiple splice variants. We have shown that Tregs from patients with amyotrophic lateral sclerosis (ALS) have reduced expression of full-length (FL) FoxP3, while other truncated splice variants are expressed predominantly. A correlation was observed between the reduced number of Tregs in the peripheral blood of ALS patients, reduced total FoxP3 mRNA, and reduced mRNA of its FL splice variant. Induction of FL FoxP3 was achieved using splice-switching oligonucleotides capable of base pairing with FoxP3 pre-mRNA and selectively modulating the inclusion of exons 2 and 7 in the mature mRNA. Selective expression of FL FoxP3 resulted in the induction of CD127[low], CD152, and Helios-positive cells, while the cell markers CD4 and CD25 were not altered. Such Tregs had an increased proliferative activity and a higher frequency of cell divisions per day. The increased suppressive activity of Tregs with the induced FL FoxP3 splice variant was associated with the increased synthesis of the pro-apoptotic granzymes A and B, and perforin, IL-10, and IL-35, which are responsible for contact-independent suppression, and with the increased ability to suppress telomerase in target cells. The upregulation of Treg suppressive and proliferative activity using splice-switching oligonucleotides to induce the predominant expression of the FoxP3 FL variant is a promising approach for regenerative cell therapy in Treg-associated diseases.}, } @article {pmid38790979, year = {2024}, author = {Mishra, PS and Phaneuf, D and Boutej, H and Picher-Martel, V and Dupre, N and Kriz, J and Julien, JP}, title = {Inhibition of NF-κB with an Analog of Withaferin-A Restores TDP-43 Homeostasis and Proteome Profiles in a Model of Sporadic ALS.}, journal = {Biomedicines}, volume = {12}, number = {5}, pages = {}, pmid = {38790979}, issn = {2227-9059}, support = {143275/CAPMC/CIHR/Canada ; 231575//Canada Research Chairs/ ; }, abstract = {The current knowledge on pathogenic mechanisms in amyotrophic lateral sclerosis (ALS) has widely been derived from studies with cell and animal models bearing ALS-linked genetic mutations. However, it remains unclear to what extent these disease models are of relevance to sporadic ALS. Few years ago, we reported that the cerebrospinal fluid (CSF) from sporadic ALS patients contains toxic factors for disease transmission in mice via chronic intracerebroventricular (i.c.v.) infusion. Thus a 14-day i.c.v. infusion of pooled CSF samples from ALS cases in mice provoked motor impairment as well as ALS-like pathological features. This offers a unique paradigm to test therapeutics in the context of sporadic ALS disease. Here, we tested a new Withaferin-A analog (IMS-088) inhibitor of NF-κB that was found recently to mitigate disease phenotypes in mouse models of familial disease expressing TDP-43 mutant. Our results show that oral intake of IMS-088 ameliorated motor performance of mice infused with ALS-CSF and it alleviated pathological changes including TDP-43 proteinopathy, neurofilament disorganization, and neuroinflammation. Moreover, CSF infusion experiments were carried out with transgenic mice having neuronal expression of tagged ribosomal protein (hNfL-RFP mice), which allowed immunoprecipitation of neuronal ribosomes for analysis by mass spectrometry of the translational peptide signatures. The results indicate that treatment with IMS-088 prevented many proteomic alterations associated with exposure to ALS-CSF involving pathways related to cytoskeletal changes, inflammation, metabolic dysfunction, mitochondria, UPS, and autophagy dysfunction. The effective disease-modifying effects of this drug in a mouse model based on i.c.v. infusion of ALS-CSF suggest that the NF-κB signaling pathway represents a compelling therapeutic target for sporadic ALS.}, } @article {pmid38790450, year = {2024}, author = {Eisen, A and Pioro, EP and Goutman, SA and Kiernan, MC}, title = {Nanoplastics and Neurodegeneration in ALS.}, journal = {Brain sciences}, volume = {14}, number = {5}, pages = {}, pmid = {38790450}, issn = {2076-3425}, support = {R01 TS000327/TS/ATSDR CDC HHS/United States ; R01 ES030049/ES/NIEHS NIH HHS/United States ; R01 NS120926/NS/NINDS NIH HHS/United States ; R01 NS127188/NS/NINDS NIH HHS/United States ; R01 TS000344/TS/ATSDR CDC HHS/United States ; }, abstract = {Plastic production, which exceeds one million tons per year, is of global concern. The constituent low-density polymers enable spread over large distances and micro/nano particles (MNPLs) induce organ toxicity via digestion, inhalation, and skin contact. Particles have been documented in all human tissues including breast milk. MNPLs, especially weathered particles, can breach the blood-brain barrier, inducing neurotoxicity. This has been documented in non-human species, and in human-induced pluripotent stem cell lines. Within the brain, MNPLs initiate an inflammatory response with pro-inflammatory cytokine production, oxidative stress with generation of reactive oxygen species, and mitochondrial dysfunction. Glutamate and GABA neurotransmitter dysfunction also ensues with alteration of excitatory/inhibitory balance in favor of reduced inhibition and resultant neuro-excitation. Inflammation and cortical hyperexcitability are key abnormalities involved in the pathogenic cascade of amyotrophic lateral sclerosis (ALS) and are intricately related to the mislocalization and aggregation of TDP-43, a hallmark of ALS. Water and many foods contain MNPLs and in humans, ingestion is the main form of exposure. Digestion of plastics within the gut can alter their properties, rendering them more toxic, and they cause gut microbiome dysbiosis and a dysfunctional gut-brain axis. This is recognized as a trigger and/or aggravating factor for ALS. ALS is associated with a long (years or decades) preclinical period and neonates and infants are exposed to MNPLs through breast milk, milk substitutes, and toys. This endangers a time of intense neurogenesis and establishment of neuronal circuitry, setting the stage for development of neurodegeneration in later life. MNPL neurotoxicity should be considered as a yet unrecognized risk factor for ALS and related diseases.}, } @article {pmid38788983, year = {2024}, author = {de Holanda Paranhos, L and Magalhães, RSS and de Araújo Brasil, A and Neto, JRM and Ribeiro, GD and Queiroz, DD and Dos Santos, VM and Eleutherio, ECA}, title = {The familial amyotrophic lateral sclerosis-associated A4V SOD1 mutant is not able to regulate aerobic glycolysis.}, journal = {Biochimica et biophysica acta. General subjects}, volume = {1868}, number = {8}, pages = {130634}, doi = {10.1016/j.bbagen.2024.130634}, pmid = {38788983}, issn = {1872-8006}, mesh = {*Glycolysis ; *Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology ; Humans ; *Superoxide Dismutase-1/genetics/metabolism ; *Saccharomyces cerevisiae/genetics/metabolism ; Glucose/metabolism ; Mutation ; }, abstract = {Under certain stress conditions, astrocytes operate in aerobic glycolysis, a process controlled by pyruvate dehydrogenase (PDH) inhibition through its E1 α subunit (Pda1) phosphorylation. This supplies lactate to neurons, which save glucose to obtain NADPH to, among other roles, counteract reactive oxygen species. A failure in this metabolic cooperation causes severe damage to neurons. In this work, using humanized Saccharomyces cerevisiae cells in which its endogenous Cu/Zn Superoxide Dismutase (SOD1) was replaced by human ortholog, we investigated the role of human SOD1 (hSOD1) in aerobic glycolysis regulation and its implications to amyotrophic lateral sclerosis (ALS), a neurodegenerative disease. Yeast cells ferment glucose even in the presence of oxygen and switch to respiratory metabolism after glucose exhaustion. However, like cells of SOD1-knockout strain, cells expressing A4V mutant of hSOD1 growing on glucose showed a respiratory phenotype, i.e., low glucose and high oxygen consumptions and low intracellular oxidation levels in response to peroxide stress, contrary to cells expressing wild-type (WT) SOD1 (yeast or human). The A4V mutation in hSOD1 is linked to ALS. In contrast to WT SOD1 strains, PDH activity of both sod1Δ and A4V hSOD1 cells did not change in response to a metabolic shift toward oxidative metabolism, which was associated to lower Pda1 phosphorylation levels under growth on glucose. Taken together, our results suggest that A4V mutant cannot regulate aerobic glycolysis via Pda1 phosphorylation the same way WT hSOD1, which might be linked to problems observed in the motor neurons of ALS patients with the SOD1 A4V mutation.}, } @article {pmid38788796, year = {2024}, author = {Togawa, N and Ayaki, T and Yoshii, D and Maki, T and Sawamoto, N and Takahashi, R}, title = {TMEM119-positive microglia were increased in the brains of patients with amyotrophic lateral sclerosis.}, journal = {Neuroscience letters}, volume = {833}, number = {}, pages = {137829}, doi = {10.1016/j.neulet.2024.137829}, pmid = {38788796}, issn = {1872-7972}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism/pathology ; *Microglia/metabolism/pathology ; Male ; Female ; Aged ; Middle Aged ; *Membrane Proteins/metabolism ; *Brain/pathology/metabolism ; Macrophages/metabolism/pathology ; Receptors, CCR2/metabolism ; White Matter/pathology/metabolism ; Spinal Cord/metabolism/pathology ; Aged, 80 and over ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder that has been reported to be affected by inflammatory cells, such as microglia and macrophages, through the concept of non-cell autonomous neuronal death. Resident microglia in the human brain and monocyte-derived macrophages (MoDM) infiltrating in tissues are difficult to distinguish. Therefore, the effects of microglia and MoDMs in ALS remain poorly understood. This study aimed to investigate the role of resident microglia and MoDMs in the pathogenesis of ALS using postmortem brain and spinal cord samples. The samples used for immunohistochemical analysis included 11 cases of sporadic ALS and 11 age-matched controls. We stained the cells with TMEM119 to detect resident microglia and CCR2 to detect MoDMs. In ALS cases, TMEM119-immunopositive resident microglia were abundant in the motor cortex and subcortical white matter (SWM) of the motor area, whereas CCR2-immunopositive MoDM was similar to control cases. In addition, the mean density of CD68-immunopositive cells in the SWM significantly correlated with the mean density of pTDP-43-positive GCIs. These results suggest that resident microglial activation plays an important role in the cerebral pathogenesis of ALS and may provide novel therapeutic strategies to target excessive activation of resident microglia in ALS.}, } @article {pmid38788509, year = {2024}, author = {Valeriano, MC and Neto, AM and Batista, ACF and Mamián-López, MB}, title = {Raman spectra soft modeling of the biodiesel oxidation through evolving factor analysis & multivariate curve resolution.}, journal = {Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy}, volume = {318}, number = {}, pages = {124498}, doi = {10.1016/j.saa.2024.124498}, pmid = {38788509}, issn = {1873-3557}, abstract = {The oxidative stability of biodiesel is defined by its relative resistance to the action of oxygen at room temperature. Its determination is an essential reference to the quality of biofuel and a significant parameter to be determined. This parameter concerns the quality of the biodiesel to be supplied to the consumer, and its determination is fundamental to maintaining the engine's proper functioning. Raman spectroscopy allows the rapid obtaining of structural information regarding biodiesel quality and, when aided by multivariate analysis methods, allows a quantitative determination of specific properties. This work uses Raman spectroscopy, Multivariate Curve Resolution with Alternative Least Squares (MCR-ALS) method, and Evolving Factor Analysis (EFA) to study biodiesel's oxidation kinetics. Also, the vibrational modes C = C, CH2, and CH3 were identified as the main structural groups involved in this process, corroborating previous studies. The MCR-ALS & EFA combination allowed modeling of the degradation kinetics following an A → B → C mechanism, where A corresponds to the biodiesel (starting material), B is related to the hydroperoxide mixture, and C is the final product. The results also suggested that this process follows a first-order reaction, with kinetic constant values of k1 = 0.0056 min[-1] and k2 = 0.0031 min[-1].}, } @article {pmid38788288, year = {2024}, author = {van Neerven, GJL and Schelling, WJ and van den Borne, K and Bijleveld, K and Baars, A and Flink, H and Gilissen, LPL}, title = {The periprocedural respiratory safety of propofol sedation in patients with a motor neuron disease undergoing percutaneous endoscopic gastrostomy insertion.}, journal = {Journal of the neurological sciences}, volume = {461}, number = {}, pages = {123049}, doi = {10.1016/j.jns.2024.123049}, pmid = {38788288}, issn = {1878-5883}, mesh = {Humans ; Male ; Female ; Aged ; *Gastrostomy/adverse effects/methods ; *Propofol/adverse effects/administration & dosage/therapeutic use ; Retrospective Studies ; *Motor Neuron Disease ; Middle Aged ; *Hypnotics and Sedatives/adverse effects ; Pneumonia, Aspiration/etiology ; Aged, 80 and over ; Enteral Nutrition/methods/adverse effects ; }, abstract = {Motor neuron diseases (MND), such as Amyotrophic Lateral Sclerosis (ALS) and Primary Lateral Sclerosis (PLS), may cause swallowing and respiratory problems, due to muscle weakness. Chronic enteral feeding via percutaneous endoscopic gastrostomy (PEG) is often indicated in these patients. PEG insertion is normally performed with sedation. Some guidelines withhold sedation in MND patients, due to the risk of respiratory complications. These guidelines seem to be defensive however and evidence is lacking. Our aim was to examine periprocedural respiratory complications occurring in MND patients undergoing PEG insertion with propofol sedation. A retrospective monocentre study was conducted in a referral hospital with an experienced PEG team. Patients with MND who underwent PEG insertion with propofol sedation between January 1. 2016 to January 1. 2023 were analysed to identify periprocedural respiratory complications. 46 patients were included. In five patients (10.9%) respiratory adverse events (AE) occurred, of which two serious (4.3%) and four AE (8.7%). Serious AE (SAE) were fatal in both cases: aspiration pneumonia (2.2%) and hypercapnia (2.2%) a few days after insertion. Sedation may have influenced the first case. Respiratory AE consisted of desaturation in two (4.3%), mild aspiration pneumonia in one (2.2%), and apnea in one patient (2.2%). Compared to previous studies respiratory complications and mortality had comparable prevalences.}, } @article {pmid38788085, year = {2024}, author = {Mohassel, P and Abdullah, M and Eichler, FS and Dunn, TM}, title = {Serine Palmitoyltransferase (SPT)-related Neurodegenerative and Neurodevelopmental Disorders.}, journal = {Journal of neuromuscular diseases}, volume = {11}, number = {4}, pages = {735-747}, pmid = {38788085}, issn = {2214-3602}, mesh = {Humans ; Amyotrophic Lateral Sclerosis/genetics/metabolism ; Hereditary Sensory and Autonomic Neuropathies/genetics/metabolism/physiopathology ; *Neurodegenerative Diseases/metabolism ; *Neurodevelopmental Disorders ; *Serine C-Palmitoyltransferase/metabolism/genetics ; Spastic Paraplegia, Hereditary/genetics/metabolism ; Sphingolipids/metabolism ; }, abstract = {Motor neuron diseases and peripheral neuropathies are heterogeneous groups of neurodegenerative disorders that manifest with distinct symptoms due to progressive dysfunction or loss of specific neuronal subpopulations during different stages of development. A few monogenic, neurodegenerative diseases associated with primary metabolic disruptions of sphingolipid biosynthesis have been recently discovered. Sphingolipids are a subclass of lipids that form critical building blocks of all cellular and subcellular organelle membranes including the membrane components of the nervous system cells. They are especially abundant within the lipid portion of myelin. In this review, we will focus on our current understanding of disease phenotypes in three monogenic, neuromuscular diseases associated with pathogenic variants in components of serine palmitoyltransferase, the first step in sphingolipid biosynthesis. These include hereditary sensory and autonomic neuropathy type 1 (HSAN1), a sensory predominant peripheral neuropathy, and two neurodegenerative disorders: juvenile amyotrophic lateral sclerosis affecting the upper and lower motor neurons with sparing of sensory neurons, and a complicated form of hereditary spastic paraplegia with selective involvement of the upper motor neurons and more broad CNS neurodegeneration. We will also review our current understanding of disease pathomechanisms, therapeutic approaches, and the unanswered questions to explore in future studies.}, } @article {pmid38787599, year = {2024}, author = {Wong, JPH and Blazev, R and Ng, YK and Goodman, CA and Montgomery, MK and Watt, KI and Carl, CS and Watt, MJ and Voldstedlund, CT and Richter, EA and Crouch, PJ and Steyn, FJ and Ngo, ST and Parker, BL}, title = {Characterization of the skeletal muscle arginine methylome in health and disease reveals remodeling in amyotrophic lateral sclerosis.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {38}, number = {10}, pages = {e23647}, doi = {10.1096/fj.202400045R}, pmid = {38787599}, issn = {1530-6860}, support = {APP2009642//DHAC | National Health and Medical Research Council (NHMRC)/ ; 1185427//DHAC | National Health and Medical Research Council (NHMRC)/ ; //University of Melbourne Driving Research Momentum/ ; //Motor Neurone Disease Research Australia Charcot/ ; //Department of Anatomy and Physiology (The University of Melbourne) ECR Seeding Grant/ ; }, mesh = {*Muscle, Skeletal/metabolism/pathology ; *Arginine/metabolism/analogs & derivatives ; Humans ; *Amyotrophic Lateral Sclerosis/metabolism/genetics/pathology ; Animals ; Mice ; *Protein-Arginine N-Methyltransferases/metabolism/genetics ; Male ; Methylation ; Female ; Protein Processing, Post-Translational ; Mice, Inbred C57BL ; Proteome/metabolism ; }, abstract = {Arginine methylation is a protein posttranslational modification important for the development of skeletal muscle mass and function. Despite this, our understanding of the regulation of arginine methylation under settings of health and disease remains largely undefined. Here, we investigated the regulation of arginine methylation in skeletal muscles in response to exercise and hypertrophic growth, and in diseases involving metabolic dysfunction and atrophy. We report a limited regulation of arginine methylation under physiological settings that promote muscle health, such as during growth and acute exercise, nor in disease models of insulin resistance. In contrast, we saw a significant remodeling of asymmetric dimethylation in models of atrophy characterized by the loss of innervation, including in muscle biopsies from patients with myotrophic lateral sclerosis (ALS). Mass spectrometry-based quantification of the proteome and asymmetric arginine dimethylome of skeletal muscle from individuals with ALS revealed the largest compendium of protein changes with the identification of 793 regulated proteins, and novel site-specific changes in asymmetric dimethyl arginine (aDMA) of key sarcomeric and cytoskeletal proteins. Finally, we show that in vivo overexpression of PRMT1 and aDMA resulted in increased fatigue resistance and functional recovery in mice. Our study provides evidence for asymmetric dimethylation as a regulator of muscle pathophysiology and presents a valuable proteomics resource and rationale for numerous methylated and nonmethylated proteins, including PRMT1, to be pursued for therapeutic development in ALS.}, } @article {pmid38786016, year = {2024}, author = {Salzinger, A and Ramesh, V and Das Sharma, S and Chandran, S and Thangaraj Selvaraj, B}, title = {Neuronal Circuit Dysfunction in Amyotrophic Lateral Sclerosis.}, journal = {Cells}, volume = {13}, number = {10}, pages = {}, pmid = {38786016}, issn = {2073-4409}, mesh = {*Amyotrophic Lateral Sclerosis/physiopathology/pathology ; Humans ; *Motor Neurons/pathology/physiology ; Animals ; Nerve Net/physiopathology/pathology ; Neuromuscular Junction/physiopathology/pathology ; Disease Models, Animal ; Motor Cortex/physiopathology/pathology ; }, abstract = {The primary neural circuit affected in Amyotrophic Lateral Sclerosis (ALS) patients is the corticospinal motor circuit, originating in upper motor neurons (UMNs) in the cerebral motor cortex which descend to synapse with the lower motor neurons (LMNs) in the spinal cord to ultimately innervate the skeletal muscle. Perturbation of these neural circuits and consequent loss of both UMNs and LMNs, leading to muscle wastage and impaired movement, is the key pathophysiology observed. Despite decades of research, we are still lacking in ALS disease-modifying treatments. In this review, we document the current research from patient studies, rodent models, and human stem cell models in understanding the mechanisms of corticomotor circuit dysfunction and its implication in ALS. We summarize the current knowledge about cortical UMN dysfunction and degeneration, altered excitability in LMNs, neuromuscular junction degeneration, and the non-cell autonomous role of glial cells in motor circuit dysfunction in relation to ALS. We further highlight the advances in human stem cell technology to model the complex neural circuitry and how these can aid in future studies to better understand the mechanisms of neural circuit dysfunction underpinning ALS.}, } @article {pmid38785754, year = {2024}, author = {Alkhazaali-Ali, Z and Sahab-Negah, S and Boroumand, AR and Farkhad, NK and Khodadoust, MA and Tavakol-Afshari, J}, title = {Evaluation of the Safety and Efficacy of Repeated Mesenchymal Stem Cell Transplantations in ALS Patients by Investigating Patients' Specific Immunological and Biochemical Biomarkers.}, journal = {Diseases (Basel, Switzerland)}, volume = {12}, number = {5}, pages = {}, pmid = {38785754}, issn = {2079-9721}, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is an incurable disease. There are vigorous attempts to develop treatments to reduce the effects of this disease, and among these treatments is the transplantation of stem cells. This study aimed to retrospectively evaluate a mesenchymal stem cell (MSC) therapy cohort as a promising novel treatment modality by estimating some additional new parameters, such as immunological and biochemical factors.

METHODS: This study was designed as an open-label, one-arm cohort retrospective study to evaluate potential diagnostic biomarkers of repeated infusions of autologous-bone marrow-derived mesenchymal stem cells (BM-MSCs) in 15 confirmed patients with ALS, administered at a dose of 1 × 106 cells/kg BW with a one-month interval, in equal amounts in both an intravenous (IV) and intrathecal (IT) capacity simultaneously, via various biochemical (iron (Fe), ferritin, total-iron-binding capacity (TIBC), transferrin, and creatine kinase (CK)) and immunological parameters (tumor necrosis factor-alpha (TNF-α), neurofilament light chain (NFL), and glial-cell-derived neurotrophic factor (GDNF) levels, evaluated during the three-month follow-up period in serum and cerebrospinal fluid (CSF).

RESULTS: Our study indicated that, in the case of immunological biomarkers, TNF-α levels in the CSF showed a significant decrease at month three after transplantation compared with levels at month zero, and the p-value was p < 0.01. No statistically significant changes were observed for other immunological as well as biochemical parameters and a p-value of p > 0.05.

CONCLUSIONS: These results can indicate the potential benefit of stem cell transfusion in patients with ALS and suggest some diagnostic biomarkers. Several studies are required to approve these results.}, } @article {pmid38785539, year = {2024}, author = {Pribac, M and Motataianu, A and Andone, S and Mardale, E and Nemeth, S}, title = {Bridging the Gap: Harnessing Plant Bioactive Molecules to Target Gut Microbiome Dysfunctions in Amyotrophic Lateral Sclerosis.}, journal = {Current issues in molecular biology}, volume = {46}, number = {5}, pages = {4471-4488}, pmid = {38785539}, issn = {1467-3045}, abstract = {The correlation between neurodegenerative diseases and the gut microbiome is increasingly evident, with amyotrophic lateral sclerosis (ALS) being particularly notable for its severity and lack of therapeutic options. The gut microbiota, implicated in the pathogenesis and development of ALS, plays a crucial role in the disease. Bioactive plant molecules, specifically volatile compounds in essential oils, offer a promising therapeutic avenue due to their anti-inflammatory properties and gut-modulating effects. Our narrative review aimed to identify microbiota-associated bacteria in ALS and analyze the benefits of administering bioactive plant molecules as much-needed therapeutic options in the management of this disease. A comprehensive search of PubMed database articles published before December 2023, encompassing research on cell, human, and animal ALS models, was conducted. After selecting, analyzing, and discussing key articles, bacteria linked to ALS pathogenesis and physiopathology were identified. Notably, positively highlighted bacteria included Akkermansia muciniphila (Verrucomicrobia phylum), Faecalibacterium prausnitzii, and Butyrivibrio spp. (Firmicutes phylum). Conversely, members of the Escherichia coli spp. (Proteobacteria phylum) and Ruminococcus spp. (Firmicutes phylum) stood out negatively in respect to ALS development. These bacteria were associated with molecular changes linked to ALS pathogenesis and evolution. Bioactive plant molecules can be directly associated with improvements in the microbiome, due to their role in reducing inflammation and oxidative stress, emerging as one of the most promising natural agents for enriching present-day ALS treatments.}, } @article {pmid38785530, year = {2024}, author = {Serrano, PL and Rodrigues, TPV and Pinto, LD and Pereira, IC and Farias, IB and Cavalheiro, RBR and Mendes, PM and Peixoto, KO and Barile, JP and Seneor, DD and Correa Silva, EG and Oliveira, ASB and Pinto, WBVR and Sgobbi, P}, title = {Assessing Chitinases and Neurofilament Light Chain as Biomarkers for Adult-Onset Leukodystrophies.}, journal = {Current issues in molecular biology}, volume = {46}, number = {5}, pages = {4309-4323}, pmid = {38785530}, issn = {1467-3045}, abstract = {Leukodystrophies represent a large and complex group of inherited disorders affecting the white matter of the central nervous system. Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) is a rare leukodystrophy which still needs the proper identification of diagnostic, prognostic, and monitoring biomarkers. The aim of this study was to determine the diagnostic and prognostic value of chitinases and neurofilament light chain as biomarkers for ALSP. A cross-sectional study was performed to analyze cerebrospinal fluid levels of chitinases (chitotriosidase and chitinase 3-like 2) and neurofilament light chain in five different groups: (i) normal health individuals; (ii) patients with definitive diagnosis of ALSP and genetic confirmation; (iii) asymptomatic patients with CSF1R variants; (iv) patients with other adult-onset leukodystrophies; and (v) patients with amyotrophic lateral sclerosis (external control group). Chitinase levels showed a statistical correlation with clinical assessment parameters in ALSP patients. Chitinase levels were also distinct between ALSP and the other leukodystrophies. Significant differences were noted in the levels of chitinases and neurofilament light chain comparing symptomatic (ALSP) and asymptomatic individuals with CSF1R variants. This study is the first to establish chitinases as a potential biomarker for ALSP and confirms neurofilament light chain as a good biomarker for primary microgliopathies.}, } @article {pmid38784406, year = {2024}, author = {Keselica, M and Peřan, D and Renza, M and Duška, F and Omáčka, D and Schnaubelt, S and Lulic, I and Sýkora, R}, title = {Efficiency of two-member crews in delivering prehospital advanced life support cardiopulmonary resuscitation: A scoping review.}, journal = {Resuscitation plus}, volume = {18}, number = {}, pages = {100661}, pmid = {38784406}, issn = {2666-5204}, abstract = {BACKGROUND: Advanced Life Support (ALS) during cardiopulmonary resuscitation (CPR) for out-of-hospital cardiac arrest (OHCA) is frequently administered by two-member crews. However, ALS CPR is mostly designed for larger crews, and the feasibility and efficacy of implementing ALS guidelines for only two rescuers remain unclear.

OBJECTIVE: This scoping review aims to examine the existing evidence and identify knowledge gaps in the efficiency of pre-hospital ALS CPR performed by two-member teams.

DESIGN: A comprehensive search was undertaken across the following databases: PubMed, Web of Science, SCOPUS, Cochrane Library Trials, and ClinicalTrials.gov. The search covered publications in English or German from January 1, 2005, to November 30, 2023. The review included studies that focused on ALS CPR procedures carried out by two-member teams in adult patients in either simulated or clinical settings.

RESULTS: A total of 22 articles were included in the qualitative synthesis. Seven topics in two-person prehospital ALS/CPR delivery were identified: 1) effect of team configuration on clinical outcome and CPR quality, 2) early airway management and ventilation techniques, 3) mechanical chest compressions, 4) prefilled syringes, 5) additional equipment, 6) adaptation of recommended ALS/CPR protocols, and 7) human factors.

CONCLUSION: There is a lack of comprehensive data regarding the adaptation of the recommended ALS algorithm in CPR for two-member crews. Although simulation studies indicate potential benefits arising from the employment of mechanical chest compression devices, prefilled syringes, and automation-assisted protocols, the current evidence is too limited to support specific modifications to existing guidelines.}, } @article {pmid38784093, year = {2024}, author = {Chen, W and Liu, X and Wan, P and Chen, Z and Chen, Y}, title = {Anti-artifacts techniques for neural recording front-ends in closed-loop brain-machine interface ICs.}, journal = {Frontiers in neuroscience}, volume = {18}, number = {}, pages = {1393206}, pmid = {38784093}, issn = {1662-4548}, abstract = {In recent years, thanks to the development of integrated circuits, clinical medicine has witnessed significant advancements, enabling more efficient and intelligent treatment approaches. Particularly in the field of neuromedical, the utilization of brain-machine interfaces (BMI) has revolutionized the treatment of neurological diseases such as amyotrophic lateral sclerosis, cerebral palsy, stroke, or spinal cord injury. The BMI acquires neural signals via recording circuits and analyze them to regulate neural stimulator circuits for effective neurological treatment. However, traditional BMI designs, which are often isolated, have given way to closed-loop brain-machine interfaces (CL-BMI) as a contemporary development trend. CL-BMI offers increased integration and accelerated response speed, marking a significant leap forward in neuromedicine. Nonetheless, this advancement comes with its challenges, notably the stimulation artifacts (SA) problem inherent to the structural characteristics of CL-BMI, which poses significant challenges on the neural recording front-ends (NRFE) site. This paper aims to provide a comprehensive overview of technologies addressing artifacts in the NRFE site within CL-BMI. Topics covered will include: (1) understanding and assessing artifacts; (2) exploring the impact of artifacts on traditional neural recording front-ends; (3) reviewing recent technological advancements aimed at addressing artifact-related issues; (4) summarizing and classifying the aforementioned technologies, along with an analysis of future trends.}, } @article {pmid38782644, year = {2025}, author = {Corcia, P and Couratier, P and Ingre, C}, title = {Could PLS represent a UMN-predominant ALS syndrome?.}, journal = {Revue neurologique}, volume = {181}, number = {1-2}, pages = {52-57}, doi = {10.1016/j.neurol.2024.04.006}, pmid = {38782644}, issn = {0035-3787}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/pathology ; *Motor Neuron Disease/diagnosis/pathology/classification ; *Motor Neurons/pathology/physiology ; Diagnosis, Differential ; Syndrome ; }, abstract = {Primary lateral sclerosis (PLS) is a motor neuron condition marked by pure upper motor neuron (UMN) degeneration. PLS represents around 3% of all motor neuron diseases. Classically the prognosis of PLS is less severe than those of amyotrophic lateral sclerosis (ALS). This explains the necessity to distinguish both conditions as early as possible. The key hallmark between the two diseases is the involvement of the lower motor neuron (LMN) system which is classically considered spared in PLS contrary to ALS. Although it seemed clinically easy to distinguish PLS from ALS with the aid of clinical and complementary examinations, there is a large body of evidence highlighting that the LMN system might be impaired in PLS. This led us to suggest that PLS might be considered as an almost pure UMN ALS phenotype.}, } @article {pmid38782052, year = {2024}, author = {Bass, J and Hill, H and Jaworsky, C}, title = {Response to Green et al in reply to Bass et al's "Significant discordance in DermTech test results when paired with histopathology: Caveat emptor".}, journal = {Journal of the American Academy of Dermatology}, volume = {91}, number = {3}, pages = {e81}, doi = {10.1016/j.jaad.2024.05.038}, pmid = {38782052}, issn = {1097-6787}, mesh = {Humans ; *Dermoscopy ; Skin Neoplasms/pathology ; }, } @article {pmid38782041, year = {2024}, author = {Hogan, DB and Maxwell, CJ and Dampf, H and McGrail, K and Estabrooks, CA and Poss, JW and Bakal, JA and Hoben, M}, title = {Excess Deaths in Assisted Living and Nursing Homes during the COVID-19 Pandemic in Alberta, Canada.}, journal = {Journal of the American Medical Directors Association}, volume = {25}, number = {7}, pages = {105032}, doi = {10.1016/j.jamda.2024.105032}, pmid = {38782041}, issn = {1538-9375}, mesh = {Humans ; *COVID-19/mortality/epidemiology ; *Nursing Homes ; Alberta/epidemiology ; *Assisted Living Facilities ; Male ; Female ; Aged ; Retrospective Studies ; Aged, 80 and over ; SARS-CoV-2 ; Pandemics ; Dementia/mortality/epidemiology ; Homes for the Aged/statistics & numerical data ; Cognitive Dysfunction/mortality/epidemiology ; Mortality/trends ; }, abstract = {OBJECTIVES: Assisted living (AL) is a significant and growing congregate care option for vulnerable older adults designed to reduce the use of nursing homes (NHs). However, work on excess mortality in congregate care during the COVID-19 pandemic has primarily focused on NHs with only a few US studies examining AL. The objective of this study was to assess excess mortality among AL and NH residents with and without dementia or significant cognitive impairment in Alberta, Canada, during the first 2 years of the COVID-19 pandemic, relative to the 3 years before.

DESIGN: Population-based, retrospective cohort study.

SETTING AND PARTICIPANTS: Residents who lived in an AL or NH facility operated or contracted by the Provincial health care system to provide publicly funded care in Alberta between January 1, 2017, and December 31, 2021.

METHODS: We used administrative health care data, including Resident Assessment Instrument - Home Care (RAI-HC, AL) and Minimum Data Set 2.0 (RAI-MDS 2.0, NHs) records, linked with data on residents' vital statistics, COVID-19 testing, emergency room registrations, and hospital stays. The outcome was excess deaths during COVID-19 (ie, the number of deaths beyond that expected based on pre-pandemic data), estimated, using overdispersed Poisson generalized linear models.

RESULTS: Overall, the risk of excess mortality [adjusted incidence rate ratio (95% confidence interval)] was higher in ALs than in NHs [1.20 (1.14-1.26) vs 1.10 (1.07-1.13)]. Weekly peaks in excess deaths coincided with COVID-19 pandemic waves and were higher among those with diagnosed dementia or significant cognitive impairment in both, AL and NHs.

CONCLUSIONS AND IMPLICATIONS: Finding excess mortality within both AL and NH facilities should lead to greater focus on infection prevention and control measures across all forms of congregate housing for vulnerable older adults. The specific needs of residents with dementia in particular will have to be addressed.}, } @article {pmid38782015, year = {2024}, author = {Benatar, M and Hansen, T and Rom, D and Geist, MA and Blaettler, T and Camu, W and Kuzma-Kozakiewicz, M and van den Berg, LH and Morales, RJ and Chio, A and Andersen, PM and Pradat, PF and Lange, D and Van Damme, P and Mora, G and Grudniak, M and Elliott, M and Petri, S and Olney, N and Ladha, S and Goyal, NA and Meyer, T and Hanna, MG and Quinn, C and Genge, A and Zinman, L and Jabari, D and Shoesmith, C and Ludolph, AC and Neuwirth, C and Nations, S and Shefner, JM and Turner, MR and Wuu, J and Bennett, R and Dang, H and Sundgreen, C and , }, title = {Safety and efficacy of arimoclomol in patients with early amyotrophic lateral sclerosis (ORARIALS-01): a randomised, double-blind, placebo-controlled, multicentre, phase 3 trial.}, journal = {The Lancet. Neurology}, volume = {23}, number = {7}, pages = {687-699}, doi = {10.1016/S1474-4422(24)00134-0}, pmid = {38782015}, issn = {1474-4465}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy ; Male ; Female ; Double-Blind Method ; Middle Aged ; Aged ; *Neuroprotective Agents/therapeutic use/adverse effects ; Treatment Outcome ; Adult ; Hydroxylamines/therapeutic use/adverse effects/pharmacology ; Oxadiazoles/therapeutic use/adverse effects ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis is a progressive neurodegenerative disorder leading to muscle weakness and respiratory failure. Arimoclomol, a heat-shock protein-70 (HSP70) co-inducer, is neuroprotective in animal models of amyotrophic lateral sclerosis, with multiple mechanisms of action, including clearance of protein aggregates, a pathological hallmark of sporadic and familial amyotrophic lateral sclerosis. We aimed to evaluate the safety and efficacy of arimoclomol in patients with amyotrophic lateral sclerosis.

METHODS: ORARIALS-01 was a multinational, randomised, double-blind, placebo-controlled, parallel-group trial done at 29 centres in 12 countries in Europe and North America. Patients were eligible if they were aged 18 years or older and met El Escorial criteria for clinically possible, probable, probable laboratory-supported, definite, or familial amyotrophic lateral sclerosis; had an ALS Functional Rating Scale-Revised score of 35 or more; and had slow vital capacity at 70% or more of the value predicted on the basis of the participant's age, height, and sex. Patients were randomly assigned (2:1) in blocks of 6, stratified by use of a stable dose of riluzole or no riluzole use, to receive oral arimoclomol citrate 1200 mg/day (400 mg three times per day) or placebo. The Randomisation sequence was computer generated centrally. Investigators, study personnel, and study participants were masked to treatment allocation. The primary outcome was the Combined Assessment of Function and Survival (CAFS) rank score over 76 weeks of treatment. The primary outcome and safety were analysed in the modified intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT03491462, and is completed.

FINDINGS: Between July 31, 2018, and July 17, 2019, 287 patients were screened, 245 of whom were enrolled in the trial and randomly assigned. The modified intention-to-treat population comprised 239 patients (160 in the arimoclomol group and 79 in the placebo group): 151 (63%) were male and 88 (37%) were female; mean age was 57·6 years (SD 10·9). CAFS score over 76 weeks did not differ between groups (mean 0·51 [SD 0·29] in the arimoclomol group vs 0·49 [0·28] in the placebo group; p=0·62). Cliff's delta comparing the two groups was 0·039 (95% CI -0·116 to 0·194). Proportions of participants who died were similar between the treatment groups: 29 (18%) of 160 patients in the arimoclomol group and 18 (23%) of 79 patients in the placebo group. Most deaths were due to disease progression. The most common adverse events were gastrointestinal. Adverse events were more often deemed treatment-related in the arimoclomol group (104 [65%]) than in the placebo group (41 [52%]) and more often led to treatment discontinuation in the arimoclomol group (26 [16%]) than in the placebo group (four [5%]).

INTERPRETATION: Arimoclomol did not improve efficacy outcomes compared with placebo. Although available biomarker data are insufficient to preclude future strategies that target the HSP response, safety data suggest that a higher dose of arimoclomol would not have been tolerated.

FUNDING: Orphazyme.}, } @article {pmid38782014, year = {2024}, author = {Hardiman, O}, title = {Amyotrophic lateral sclerosis: a lesson in translation.}, journal = {The Lancet. Neurology}, volume = {23}, number = {7}, pages = {651-653}, doi = {10.1016/S1474-4422(24)00223-0}, pmid = {38782014}, issn = {1474-4465}, mesh = {*Amyotrophic Lateral Sclerosis/therapy ; Humans ; Translational Research, Biomedical ; }, } @article {pmid38781481, year = {2025}, author = {Zeng, Y and Guo, R and Cao, S and Chavarria Gonzalez, S and Pang, K and Liu, C and Yang, H}, title = {Mendelian randomization study supports relative carbohydrate intake as an independent risk factor for amyotrophic lateral sclerosis.}, journal = {Nutritional neuroscience}, volume = {28}, number = {1}, pages = {116-124}, doi = {10.1080/1028415X.2024.2352196}, pmid = {38781481}, issn = {1476-8305}, support = {G9815508/MRC_/Medical Research Council/United Kingdom ; MC_PC_15018/MRC_/Medical Research Council/United Kingdom ; MC_PC_19009/MRC_/Medical Research Council/United Kingdom ; }, mesh = {*Amyotrophic Lateral Sclerosis/genetics ; Humans ; *Mendelian Randomization Analysis ; *Dietary Carbohydrates/administration & dosage ; Risk Factors ; *Genome-Wide Association Study ; Polymorphism, Single Nucleotide ; Diet ; Dietary Fats/administration & dosage ; Dietary Proteins/administration & dosage ; }, abstract = {OBJECTIVES: Observational studies suggested a potential correlation between dietary intake and amyotrophic lateral sclerosis (ALS), but conflicting findings exist and causality remains unclear. Here, we performed a Mendelian randomization (MR) analysis to evaluate the causal impact of relative intake of (i) carbohydrate, (ii) fat, and (iii) protein on ALS risk.

METHODS: The genome-wide association summary statistics of three dietary macronutrient intake traits and ALS were obtained. Initially, forward and reverse univariable MR (UVMR) analysis were conducted using the inverse variance weighted (IVW) method as the primary approach, supplemented by MR-Egger, weighted median, and maximum likelihood. Subsequently, multivariable MR (MVMR) analysis was performed to assess the independent causal effects of each dietary. Additionally, diverse sensitivity tests were conducted to evaluate the reliability of the MR analyses.

RESULTS: The forward UVMR analysis conducted by IVW indicated that relative carbohydrate intake significantly increased ALS risk. Furthermore, results from three other MR methods paralleled those from IVW. However, the other two dietary intake traits did not have a causative impact on ALS risk. The reverse UVMR analysis indicated that ALS did not causatively influence the three dietary intake traits. The MVMR analysis showed that after adjusting for the effects of the other two dietary intake traits, relative carbohydrate intake independently and significantly increased ALS risk. Sensitivity tests indicated no significant heterogeneity or horizontal pleiotropy.

DISCUSSION: MR analysis supported relative carbohydrate independently increasing ALS risk. Nevertheless, further validation of this finding in future large cohorts is required.}, } @article {pmid38780855, year = {2024}, author = {Burgio, F and Danesin, L and Wennberg, A and Tonini, E and Galetto, V and Sivieri, S and Giustiniani, A and Palmer, K and Meneghello, F and Sorarù, G and Zettin, M and Arcara, G and Benavides-Varela, S and Semenza, C}, title = {Financial and numerical abilities: patterns of dissociation in neurological and psychiatric diseases.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {45}, number = {10}, pages = {4779-4787}, pmid = {38780855}, issn = {1590-3478}, support = {GR-2018-12367927//Ministero della Salute/ ; }, mesh = {Humans ; Male ; Female ; Middle Aged ; *Neuropsychological Tests ; Adult ; Aged ; Cognitive Dysfunction/etiology/physiopathology ; Mental Disorders/economics ; Schizophrenia/physiopathology/complications ; Brain Injuries, Traumatic/complications/psychology ; }, abstract = {The present work investigates whether financial abilities can be associated with numerical abilities and with general cognitive abilities. We compared performance on numerical and financial tests, and on tests routinely used to measure general cognitive performance, in healthy controls and in a group of people with heterogeneous pathological conditions including mild cognitive impairment, amyotrophic lateral sclerosis, traumatic brain injury, and schizophrenia. Patients showed lower performances in both numerical and financial abilities compared to controls. Numerical and financial skills were positively correlated in both groups, but they correlated poorly with measures of general cognitive functioning. Crucially, only basic financial tasks -such as counting currencies- but not advanced ones -like financial judgments- were associated with numerical or general cognitive functioning in logistic regression analyses. Conversely, advanced financial abilities, but not basic ones, were associated with abstract reasoning. At a qualitative analysis, we found that deficits in numerical and financial abilities might double dissociate. Similarly, we observed double dissociations between difficulties in financial abilities and cognitive deficits. In conclusion, financial abilities may be independent of numerical skills, and financial deficits are not always related to the presence of cognitive difficulties. These findings are important for both clinical and legal practice.}, } @article {pmid38780595, year = {2024}, author = {da Gama, NAS and Queiroz, GAMC and de Alcântara, C and Cruzeiro, MM and Alencar, MA and Martins de Araújo, C and Gomide, GFD and de Souza, LC and Jaeger, A}, title = {Memory for emotional information in sporadic and Type 8 amyotrophic lateral sclerosis.}, journal = {Neuropsychology}, volume = {38}, number = {5}, pages = {465-474}, doi = {10.1037/neu0000957}, pmid = {38780595}, issn = {1931-1559}, support = {//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; //Fundação de Amparo à Pesquisa do Estado de São Paulo/ ; //Coordenação de Aperfeiçoamento de Pessoal de Nível Superior/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/psychology/physiopathology ; Male ; Female ; Middle Aged ; *Emotions/physiology ; Aged ; *Recognition, Psychology/physiology ; Memory Disorders/etiology/diagnosis ; Adult ; Memory, Episodic ; Neuropsychological Tests ; }, abstract = {OBJECTIVE: Amyotrophic lateral sclerosis (ALS) is often shown to cause episodic memory deficits. Here, we investigated whether such memory deficits are differentially expressed according to the emotional valence of stimuli and whether they are similarly reproduced in both individuals with sporadic ALS (sALS) and familial Type 8 ALS (ALS8).

METHOD: Twenty individuals with sALS, 18 individuals with ALS8, and 19 healthy controls were recruited for the study. After a neuropsychological and psychopathological assessment, all participants responded to a recognition memory test wherein images varying in terms of valence were initially shown. After a short interval, the images were shown again intermixed with new images, and the participants' task was to indicate whether each image was "old" or "new" and to estimate the confidence in their responses.

RESULTS: Both the sALS and the ALS8 groups showed significantly lower recognition of positive relative to negative valence images (d = 0.92 and d = 0.74, respectively), an effect that was completely absent for healthy controls (d = 0.17). These effects were qualified by a significant interaction involving the factors of valence and group (ηp² = 0.12).

CONCLUSIONS: The current findings demonstrate that sALS and ALS8 are associated with decreased recognition of emotional information, an effect that is nonetheless restricted to positive valence stimuli. (PsycInfo Database Record (c) 2024 APA, all rights reserved).}, } @article {pmid38779803, year = {2024}, author = {Zhu, L and Bai, D and Wang, X and Ou, K and Li, B and Jia, Q and Tan, Z and Liang, J and He, D and Yan, S and Wang, L and Li, S and Li, XJ and Yin, P}, title = {Pathologic TDP-43 downregulates myelin gene expression in the monkey brain.}, journal = {Brain pathology (Zurich, Switzerland)}, volume = {34}, number = {6}, pages = {e13277}, pmid = {38779803}, issn = {1750-3639}, support = {32270564//National Natural Science Foundation of China/ ; 81830032//National Natural Science Foundation of China/ ; 82071421//National Natural Science Foundation of China/ ; 82394422//National Natural Science Foundation of China/ ; 2021ZT09Y007//Department of Science and Technology of Guangdong Province/ ; 2018B030337001//Department of Science and Technology of Guangdong Province/ ; 2022A1515011205//Basic and Applied Basic Research Foundation of Guangdong Province/ ; 2023A1515010811//Basic and Applied Basic Research Foundation of Guangdong Province/ ; }, mesh = {Animals ; Male ; *Brain/metabolism/pathology ; Corpus Callosum/metabolism/pathology ; Demyelinating Diseases/pathology/metabolism/genetics ; *DNA-Binding Proteins/metabolism/genetics ; Down-Regulation ; Myelin Sheath/metabolism/pathology/genetics ; Oligodendroglia/metabolism/pathology ; Macaca fascicularis ; }, abstract = {Growing evidence indicates that non-neuronal oligodendrocyte plays an important role in Amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases. In patient's brain, the impaired myelin structure is a pathological feature with the observation of TDP-43 in cytoplasm of oligodendrocyte. However, the mechanism underlying the gain of function by TDP-43 in oligodendrocytes, which are vital for the axonal integrity, remains unclear. Recently, we found that the primate-specific cleavage of truncated TDP-43 fragments occurred in cytoplasm of monkey neural cells. This finding opened up the avenue to investigate the myelin integrity affected by pathogenic TDP-43 in oligodendrocytes. In current study, we demonstrated that the truncated TDP-35 in oligodendrocytes specifically, could lead to the dysfunctional demyelination in corpus callosum of monkey. As a consequence of the interaction of myelin regulatory factor with the accumulated TDP-35 in cytoplasm, the downstream myelin-associated genes expression was downregulated at the transcriptional level. Our study aims to investigate the potential effect on myelin structure injury, affected by the truncated TDP-43 in oligodendrocyte, which provided the additional clues on the gain of function during the progressive pathogenesis and symptoms in TDP-43 related diseases.}, } @article {pmid38779353, year = {2024}, author = {Trubshaw, M and Gohil, C and Yoganathan, K and Kohl, O and Edmond, E and Proudfoot, M and Thompson, AG and Talbot, K and Stagg, CJ and Nobre, AC and Woolrich, M and Turner, MR}, title = {The cortical neurophysiological signature of amyotrophic lateral sclerosis.}, journal = {Brain communications}, volume = {6}, number = {3}, pages = {fcae164}, pmid = {38779353}, issn = {2632-1297}, abstract = {The progressive loss of motor function characteristic of amyotrophic lateral sclerosis is associated with widespread cortical pathology extending beyond primary motor regions. Increasing muscle weakness reflects a dynamic, variably compensated brain network disorder. In the quest for biomarkers to accelerate therapeutic assessment, the high temporal resolution of magnetoencephalography is uniquely able to non-invasively capture micro-magnetic fields generated by neuronal activity across the entire cortex simultaneously. This study examined task-free magnetoencephalography to characterize the cortical oscillatory signature of amyotrophic lateral sclerosis for having potential as a pharmacodynamic biomarker. Eight to ten minutes of magnetoencephalography in the task-free, eyes-open state was recorded in amyotrophic lateral sclerosis (n = 36) and healthy age-matched controls (n = 51), followed by a structural MRI scan for co-registration. Extracted magnetoencephalography metrics from the delta, theta, alpha, beta, low-gamma, high-gamma frequency bands included oscillatory power (regional activity), 1/f exponent (complexity) and amplitude envelope correlation (connectivity). Groups were compared using a permutation-based general linear model with correction for multiple comparisons and confounders. To test whether the extracted metrics could predict disease severity, a random forest regression model was trained and evaluated using nested leave-one-out cross-validation. Amyotrophic lateral sclerosis was characterized by reduced sensorimotor beta band and increased high-gamma band power. Within the premotor cortex, increased disability was associated with a reduced 1/f exponent. Increased disability was more widely associated with increased global connectivity in the delta, theta and high-gamma bands. Intra-hemispherically, increased disability scores were particularly associated with increases in temporal connectivity and inter-hemispherically with increases in frontal and occipital connectivity. The random forest model achieved a coefficient of determination (R[2]) of 0.24. The combined reduction in cortical sensorimotor beta and rise in gamma power is compatible with the established hypothesis of loss of inhibitory, GABAergic interneuronal circuits in pathogenesis. A lower 1/f exponent potentially reflects a more excitable cortex and a pathology unique to amyotrophic lateral sclerosis when considered with the findings published in other neurodegenerative disorders. Power and complexity changes corroborate with the results from paired-pulse transcranial magnetic stimulation. Increased magnetoencephalography connectivity in worsening disability is thought to represent compensatory responses to a failing motor system. Restoration of cortical beta and gamma band power has significant potential to be tested in an experimental medicine setting. Magnetoencephalography-based measures have potential as sensitive outcome measures of therapeutic benefit in drug trials and may have a wider diagnostic value with further study, including as predictive markers in asymptomatic carriers of disease-causing genetic variants.}, } @article {pmid38778614, year = {2025}, author = {Zhou, H and Xia, Y and Zhu, R and Zhang, Y and Zhang, X and Zhang, Y and Wang, J}, title = {Ribosomal DNA and Neurological Disorders.}, journal = {Current molecular medicine}, volume = {25}, number = {5}, pages = {556-566}, pmid = {38778614}, issn = {1875-5666}, support = {G2022027010L//Ministry of Science and Technology of the People's Republic of China/ ; 82061138005//National Natural Science Foundation of China/ ; T2020009, 337/370//Hubei Provincial Department of Education/ ; }, mesh = {Humans ; *Nervous System Diseases/genetics/metabolism/pathology ; *DNA, Ribosomal/genetics/metabolism ; Animals ; Huntington Disease/genetics ; }, abstract = {Ribosomal DNA (rDNA) is important in the nucleolus and nuclear organization of human cells. Defective rDNA repeat maintenance has been reported to be closely associated with neurological disorders, such as Alzheimer's disease, Huntington's disease, Parkinson's disease, amyotrophic lateral sclerosis, frontotemporal dementia, depression, suicide, etc. However, there has not been a comprehensive review on the role of rDNA in these disorders. In this review, we have summarized the role of rDNA in major neurological disorders to sort out the correlation between rDNA and neurological diseases and provided insights for therapy with rDNA as a target.}, } @article {pmid38778595, year = {2025}, author = {Jayaprakash, B and Savira, M and Mahmood, AAR and Prasanna, M}, title = {The Role of Stem Cell Therapies in the Treatment of Neurodegenerative Diseases.}, journal = {Current stem cell research & therapy}, volume = {20}, number = {2}, pages = {146-165}, doi = {10.2174/011574888X313112240510160102}, pmid = {38778595}, issn = {2212-3946}, mesh = {Humans ; *Neurodegenerative Diseases/therapy ; *Stem Cell Transplantation/methods ; Animals ; Neural Stem Cells/transplantation ; Parkinson Disease/therapy ; }, abstract = {Cellular replacement therapy and genetic transfer in injured brains provide new pathways for treating human neurological illnesses. Current progress in the field focuses on the production of neurons and glial cells from many types of stem cells, such as embryonic, induced pluripotent, mesenchymal, and neural stem cells. This has led to a significant increase in research on brain transplantation treatments. Extended neurodegeneration results in the progressive decline of certain neuronal subtypes or whole neuronal cells. An analysis of the progress made in induced pluripotent and mesenchymal stem cells reveals their significant promise in disease modeling, regeneration, and medication screening. The requirement for stem cells in neurodegenerative disease studies has been crucial in recent years. Stem cells provide the potential for replacing impaired neurons, comprehending disease needs modeling, and creating efficient treatments, but they have many challenges in culturing and acceptability to the host immune cells. The need to use their potential in discovering novel therapies for diseases such as Alzheimer's, Parkinson's, and amyotrophic lateral sclerosis leads to promising therapy. This review examines the function of stem cells in the pathogenesis and treatment of Huntington's disease, Parkinson's disease, Alzheimer's disease, and multiple sclerosis. This review further examines hurdles such as immunological reactions and delivery systems intending to overcome these problems. This article offers a detailed viewpoint on the use of stem cell-based nanotherapies as revolutionary treatments for various neurological illnesses.}, } @article {pmid38778483, year = {2024}, author = {Yan, J and Chen, H and Zhang, Y and Peng, L and Wang, Z and Lan, X and Yu, S and Yang, Y}, title = {Fecal microbiota transplantation significantly improved respiratory failure of amyotrophic lateral sclerosis.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2353396}, pmid = {38778483}, issn = {1949-0984}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy/microbiology ; Bacteroides ; Faecalibacterium prausnitzii ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Gastrointestinal Microbiome ; Respiration, Artificial ; *Respiratory Insufficiency/therapy/microbiology ; Treatment Outcome ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that leads to respiratory failure, and eventually death. However, there is a lack of effective treatments for ALS. Here we report the results of fecal microbiota transplantation (FMT) in two patients with late-onset classic ALS with a Japan ALS severity classification of grade 5 who required tracheostomy and mechanical ventilation. In both patients, significant improvements in respiratory function were observed following two rounds of FMT, leading to weaning off mechanical ventilation. Their muscle strength improved, allowing for assisted standing and mobility. Other notable treatment responses included improved swallowing function and reduced muscle fasciculations. Metagenomic and metabolomic analysis revealed an increase in beneficial Bacteroides species (Bacteroides stercoris, Bacteroides uniformis, Bacteroides vulgatus), and Faecalibacterium prausnitzii after FMT, as well as elevated levels of metabolites involved in arginine biosynthesis and decreased levels of metabolites involved in branched-chain amino acid biosynthesis. These findings offer a potential rescue therapy for ALS with respiratory failure and provide new insights into ALS in general.}, } @article {pmid38777640, year = {2024}, author = {Zhu, J and Yan, Y and Jiang, W and Zhang, S and Niu, X and Wan, S and Cong, Y and Hu, X and Zheng, B and Yang, Y}, title = {A Deep Learning Model for Automatically Quantifying the Anterior Segment in Ultrasound Biomicroscopy Images of Implantable Collamer Lens Candidates.}, journal = {Ultrasound in medicine & biology}, volume = {50}, number = {8}, pages = {1262-1272}, doi = {10.1016/j.ultrasmedbio.2024.05.004}, pmid = {38777640}, issn = {1879-291X}, mesh = {Humans ; *Microscopy, Acoustic/methods ; *Deep Learning ; *Anterior Eye Segment/diagnostic imaging ; Male ; Female ; Adult ; Phakic Intraocular Lenses ; Lens Implantation, Intraocular ; Young Adult ; Middle Aged ; Image Processing, Computer-Assisted/methods ; }, abstract = {OBJECTIVE: This study aimed to develop and evaluate a deep learning-based model that could automatically measure anterior segment (AS) parameters on preoperative ultrasound biomicroscopy (UBM) images of implantable Collamer lens (ICL) surgery candidates.

METHODS: A total of 1164 panoramic UBM images were preoperatively obtained from 321 patients who received ICL surgery in the Eye Center of Renmin Hospital of Wuhan University (Wuhan, China) to develop an imaging database. First, the UNet++ network was utilized to segment AS tissues automatically, such as corneal lens and iris. In addition, image processing techniques and geometric localization algorithms were developed to automatically identify the anatomical landmarks (ALs) of pupil diameter (PD), anterior chamber depth (ACD), angle-to-angle distance (ATA), and sulcus-to-sulcus distance (STS). Based on the results of the latter two processes, PD, ACD, ATA, and STS can be measured. Meanwhile, an external dataset of 294 images from Huangshi Aier Eye Hospital was employed to further assess the model's performance in other center. Lastly, a subset of 100 random images from the external test set was chosen to compare the performance of the model with senior experts.

RESULTS: Whether in the internal test dataset or external test dataset, using manual labeling as the reference standard, the models achieved a mean Dice coefficient exceeding 0.880. Additionally, the intra-class correlation coefficients (ICCs) of ALs' coordinates were all greater than 0.947, and the percentage of Euclidean distance distribution of ALs within 250 μm was over 95.24%.While the ICCs for PD, ACD, ATA, and STS were greater than 0.957, furthermore, the average relative error (ARE) of PD, ACD, ATA, and STS were below 2.41%. In terms of human versus machine performance, the ICCs between the measurements performed by the model and those by senior experts were all greater than 0.931.

CONCLUSION: A deep learning-based model could measure AS parameters using UBM images of ICL candidates, and exhibited a performance similar to that of a senior ophthalmologist.}, } @article {pmid38777186, year = {2024}, author = {Green, LJ and Brouha, B and Bhatia, N}, title = {Response to Bass et al's "Significant discordance in DermTech test results when paired with histopathology: Caveat emptor".}, journal = {Journal of the American Academy of Dermatology}, volume = {91}, number = {3}, pages = {e79}, doi = {10.1016/j.jaad.2024.02.067}, pmid = {38777186}, issn = {1097-6787}, mesh = {Humans ; *Skin Neoplasms/pathology ; Dermoscopy ; Melanoma/pathology ; }, } @article {pmid38776614, year = {2024}, author = {López-Figueroa, C and Domingo, M and Duignan, PJ and Cuvertoret-Sanz, M and Martí-García, B and Pintado, E and Martinez, M and Martínez, J}, title = {Air leak syndrome in animals: definition and pathogenesis.}, journal = {Journal of comparative pathology}, volume = {211}, number = {}, pages = {42-51}, doi = {10.1016/j.jcpa.2024.04.005}, pmid = {38776614}, issn = {1532-3129}, mesh = {Animals ; Cats ; *Pneumothorax/veterinary/etiology ; Dogs ; Mediastinal Emphysema/veterinary ; Retrospective Studies ; Cat Diseases/pathology ; Dog Diseases/pathology ; Female ; Male ; Subcutaneous Emphysema/veterinary/etiology ; Pneumoperitoneum/veterinary ; }, abstract = {Air leak syndrome (ALS) is described in human medicine as a constellation of clinical disorders including pneumomediastinum, pneumopericardium, pulmonary interstitial emphysema, pneumothorax, pneumoperitoneum, pneumoretroperitoneum and subcutaneous emphysema. The pathogenesis of ALS depends on the anatomy of the mediastinum and its associations with thoracic, abdominal and cervical connective tissues, as well as a physical phenomenon referred to as the Macklin effect. Various animal species develop diverse combinations of these lesions, although ALS has not been recognized in animals. However, this term aids pathologists in addressing this disease compilation. The aim of this retrospective study is to illustrate examples of ALS in animals by arbitrarily selecting 13 cases in dogs, cats, pinnipeds, sea otters and harbour porpoises. ALS can be classified into three groups based on aetiology: iatrogenic, secondary or spontaneous. Iatrogenic ALS was diagnosed in two cats with tracheal laceration following endotracheal intubation. Secondary ALS was identified in two dogs, one with acute respiratory distress syndrome and the other due to grass awn migration. Secondary ALS in pinnipeds was diagnosed following severe pulmonary parasitism, uraemic pneumonia and oesophageal perforation. The other marine mammals developed ALS following trauma. Spontaneous ALS was also diagnosed in one cat and one dog without any apparent predisposing causes.}, } @article {pmid38776297, year = {2024}, author = {Issa, NP and Aydin, S and Polley, E and Carberry, N and Garret, MA and Smith, S and Habib, AA and Baumgartner, NW and Soliven, B and Rezania, K}, title = {Intermuscular coherence as an early biomarker for amyotrophic lateral sclerosis: The protocol for a prospective, multicenter study.}, journal = {PloS one}, volume = {19}, number = {5}, pages = {e0303053}, pmid = {38776297}, issn = {1932-6203}, support = {R01 NS116262/NS/NINDS NIH HHS/United States ; }, mesh = {Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; *Amyotrophic Lateral Sclerosis/diagnosis/physiopathology ; *Biomarkers/analysis ; *Electromyography/methods ; Motor Neurons/pathology ; Muscle, Skeletal/physiopathology/pathology ; Prospective Studies ; Multicenter Studies as Topic ; }, abstract = {OBJECTIVE: To describe the protocol of a prospective study to test the validity of intermuscular coherence (IMC) as a diagnostic tool and biomarker of upper motor neuron degeneration in amyotrophic lateral sclerosis (ALS).

METHODS: This is a multicenter, prospective study. IMC of muscle pairs in the upper and lower limbs is gathered in ∼650 subjects across three groups using surface electrodes and conventional electromyography (EMG) machines. The following subjects will be tested: 1) neurotypical controls; 2) patients with symptomatology suggestive for early ALS but not meeting probable or definite ALS by Awaji Criteria; 3) patients with a known ALS mimic. The recruitment period is between 3/31/2021 and 12/31/2025. Written consent will be sought from the subject or the subject's legally authorized representative during enrollment.

RESULTS: The endpoints of this study include: 1) whether adding IMC to the Awaji ALS criteria improve its sensitivity in early ALS and can allow for diagnosis earlier; 2) constructing a database of IMC across different ages, genders, and ethnicities.

SIGNIFICANCE: This study may validate a new inexpensive, painless, and widely available tool for the diagnosis of ALS.}, } @article {pmid38775852, year = {2024}, author = {Ebrahimi, P and Davoudi, E and Sadeghian, R and Zadeh, AZ and Razmi, E and Heidari, R and Morowvat, MH and Sadeghian, I}, title = {In vivo and ex vivo gene therapy for neurodegenerative diseases: a promise for disease modification.}, journal = {Naunyn-Schmiedeberg's archives of pharmacology}, volume = {397}, number = {10}, pages = {7501-7530}, pmid = {38775852}, issn = {1432-1912}, support = {29849//Shiraz University of Medical Sciences/ ; }, mesh = {Humans ; *Genetic Therapy/methods ; Animals ; *Neurodegenerative Diseases/therapy/genetics ; Gene Editing/methods ; }, abstract = {Neurodegenerative diseases (NDDs), including AD, PD, HD, and ALS, represent a growing public health concern linked to aging and lifestyle factors, characterized by progressive nervous system damage leading to motor and cognitive deficits. Current therapeutics offer only symptomatic management, highlighting the urgent need for disease-modifying treatments. Gene therapy has emerged as a promising approach, targeting the underlying pathology of diseases with diverse strategies including gene replacement, gene silencing, and gene editing. This innovative therapeutic approach involves introducing functional genetic material to combat disease mechanisms, potentially offering long-term efficacy and disease modification. With advancements in genomics, structural biology, and gene editing tools such as CRISPR/Cas9, gene therapy holds significant promise for addressing the root causes of NDDs. Significant progress in preclinical and clinical studies has demonstrated the potential of in vivo and ex vivo gene therapy to treat various NDDs, offering a versatile and precise approach in comparison to conventional treatments. The current review describes various gene therapy approaches employed in preclinical and clinical studies for the treatment of NDDs, including AD, PD, HD, and ALS, and addresses some of the key translational challenges in this therapeutic approach.}, } @article {pmid38775303, year = {2024}, author = {Zhang, J and Yang, F and Li, M and Zhu, Y and Huang, X}, title = {Quantitative evaluation of factors influencing the 3 Hz repetitive nerve stimulation test in patients with amyotrophic lateral sclerosis.}, journal = {Muscle & nerve}, volume = {70}, number = {2}, pages = {194-203}, doi = {10.1002/mus.28165}, pmid = {38775303}, issn = {1097-4598}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology/diagnosis ; Male ; Female ; Middle Aged ; Aged ; Adult ; Electric Stimulation/methods ; Neuromuscular Junction/physiopathology ; Electromyography/methods ; }, abstract = {INTRODUCTION/AIMS: Previous studies have suggested that treatments targeting the neuromuscular junction (NMJ) may play a role in the treatment of amyotrophic lateral sclerosis (ALS). However, factors impacting repetitive nerve stimulation (RNS), a technique to evaluate NMJ function, have yet to be fully elucidated. We aimed to identify independent factors contributing to the decremental response of the accessory nerve and evaluated its value in ALS clinical practice.

METHODS: A total of 626 patients who were diagnosed with ALS and underwent 3 Hz RNS tests on the accessory nerve were enrolled. Data on their clinical and electrophysiological indicators were divided into a training set (collected from June 2016 to December 2022) and a test set (collected from January to August 2023). Stepwise regression was used in independent variable selection and model building.

RESULTS: Forty-two percent of patients had a decrement larger than 10% and 24% had a decrement larger than 15%. Onset age, sex, onset site, forced vital capacity (FVC) and motor unit potential (MUP) duration were independent factors contributing to the results of the RNS test. MUP duration had the greatest impact on decremental response, followed by FVC and onset age. The decremental response in females was larger than in males. Upper limb onset was found to contribute more to the decrement than lower limb or bulbar onset.

DISCUSSION: In patients with ALS, NMJ safety factor is reduced during re-innervation. Decremental response is affected by multiple factors, which needs to be considered in clinical trials targeting the NMJ in these patients.}, } @article {pmid38775192, year = {2024}, author = {Ju, W and Ban, JJ and Im, HR and Ko, SH and Seo, J and Min, YG and Hong, YH and Choi, SJ and Sung, JJ}, title = {Association of serum Spp1 levels with disease progression in ALS and SBMA.}, journal = {Annals of clinical and translational neurology}, volume = {11}, number = {7}, pages = {1809-1818}, pmid = {38775192}, issn = {2328-9503}, support = {2018R1A5A2025964//National Research Foundation of Korea/ ; 2020R1C1C1005122//National Research Foundation of Korea/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/blood/physiopathology/diagnosis ; *Osteopontin/blood ; Male ; Female ; Middle Aged ; *Disease Progression ; Aged ; Biomarkers/blood ; Adult ; Neuroinflammatory Diseases/blood ; Cytokines/blood ; }, abstract = {OBJECTIVE: In comparison with amyotrophic lateral sclerosis (ALS), the contribution of neuroinflammation in spinobulbar muscular atrophy (SBMA) has been less explored. We investigated the role of neuroinflammation in the pathogenesis of ALS and SBMA by analyzing systemic inflammatory markers and osteopontin (Spp1).

METHODS: This study involved 105 ALS, 77 SBMA, and 55 healthy controls. We measured their systemic inflammatory markers, serum Spp1, and cytokine levels (interferon-γ, interleukin [IL]-1β, IL-6, IL-8, IL-10, tumor necrosis factor-α, and IL-17A), investigated correlations between Spp1 levels and clinical features, and evaluated ALS survival rates according to Spp1 levels.

RESULTS: In the ALS group, systemic inflammatory markers were significantly higher than in the control and SBMA groups. Spp1 levels were observed to be higher in ALS patients, but the difference was not statistically significant among the study groups. Cytokine profiles were comparable. In ALS, higher Spp1 levels were correlated with lower ALS Functional Rating Scale-Revised (ALSFRS-R) scores (r = -0.25, p = 0.02) and faster disease progression rate (r = 0.37, p < 0.001). After adjusting for other prognostic indicators, high Spp1 levels were independently associated with shorter survival in ALS patients (hazard ratio 13.65, 95% confidence interval 2.57-72.53, p < 0.01).

INTERPRETATION: Neuroinflammation does not appear to be a primary contributor to the pathogenesis of SBMA. Serum Spp1 levels may serve as a reliable biomarker for disease progression and prognosis in ALS. These findings expand our understanding of these two distinct motor neuron disorders and offer a potential biomarker for future studies.}, } @article {pmid38775181, year = {2024}, author = {Marriott, H and Spargo, TP and Al Khleifat, A and Andersen, PM and Başak, NA and Cooper-Knock, J and Corcia, P and Couratier, P and de Carvalho, M and Drory, V and Gotkine, M and Landers, JE and McLaughlin, R and Pardina, JSM and Morrison, KE and Pinto, S and Shaw, CE and Shaw, PJ and Silani, V and Ticozzi, N and van Damme, P and van den Berg, LH and Vourc'h, P and Weber, M and Veldink, JH and , and Dobson, RJ and Schwab, P and Al-Chalabi, A and Iacoangeli, A}, title = {Mutations in the tail and rod domains of the neurofilament heavy-chain gene increase the risk of ALS.}, journal = {Annals of clinical and translational neurology}, volume = {11}, number = {7}, pages = {1775-1786}, pmid = {38775181}, issn = {2328-9503}, support = {//Maudsley NHS Foundation Trust/ ; 22-PDF-609//ALS Association Milton Safenowitz Research/ ; MR/R024804/1/MRC_/Medical Research Council/United Kingdom ; //BHF British Heart Foundation/ ; //Darby Rimmer MND Foundation/ ; NIHR202421//National Institute for Health Research/ ; Al Khleifat/Oct21/975-799/MNDA_/Motor Neurone Disease Association/United Kingdom ; //MND Scotland/ ; ES/L008238/1//Economic and Social Research Council/ ; //Alan Davidson Foundation/ ; /WT_/Wellcome Trust/United Kingdom ; //Alzheimer's Research UK/ ; //Rosetrees Trust/ ; MR/L501529/1/MRC_/Medical Research Council/United Kingdom ; //My Name'5 Doddie Foundation/ ; //GlaxoSmithKline/ ; //MRC Medical Research Council/ ; //The NIHR Maudsley Biomedical Research Centre/ ; //Spastic Paraplegia Foundation/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/epidemiology ; Genetic Predisposition to Disease/genetics ; Mutation ; Mutation, Missense ; *Neurofilament Proteins/genetics ; Protein Domains/genetics ; }, abstract = {OBJECTIVE: Neurofilament heavy-chain gene (NEFH) variants are associated with multiple neurodegenerative diseases, however, their relationship with ALS has not been robustly explored. Still, NEFH is commonly included in genetic screening panels worldwide. We therefore aimed to determine if NEFH variants modify ALS risk.

METHODS: Genetic data of 11,130 people with ALS and 7,416 controls from the literature and Project MinE were analysed. We performed meta-analyses of published case-control studies reporting NEFH variants, and variant analysis of NEFH in Project MinE whole-genome sequencing data.

RESULTS: Fixed-effects meta-analysis found that rare (MAF <1%) missense variants in the tail domain of NEFH increase ALS risk (OR 4.55, 95% CI 2.13-9.71, p < 0.0001). In Project MinE, ultrarare NEFH variants increased ALS risk (OR 1.37 95% CI 1.14-1.63, p = 0.0007), with rod domain variants (mostly intronic) appearing to drive the association (OR 1.45 95% CI 1.18-1.77, pMadsen-Browning = 0.0007, pSKAT-O = 0.003). While in the tail domain, ultrarare (MAF <0.1%) pathogenic missense variants were also associated with higher risk of ALS (OR 1.94, 95% CI 0.86-4.37, pMadsen-Browning = 0.039), supporting the meta-analysis results. Finally, several tail in-frame deletions were also found to affect disease risk, however, both protective and pathogenic deletions were found in this domain, highlighting an intricate architecture that requires further investigation.

INTERPRETATION: We showed that NEFH tail missense and in-frame deletion variants, and intronic rod variants are risk factors for ALS. However, they are not variants of large effect, and their functional impact needs to be clarified in further studies. Therefore, their inclusion in routine genetic screening panels should be reconsidered.}, } @article {pmid38775138, year = {2024}, author = {Calma, AD and Pavey, N and Menon, P and Vucic, S}, title = {Neuroinflammation in amyotrophic lateral sclerosis: pathogenic insights and therapeutic implications.}, journal = {Current opinion in neurology}, volume = {37}, number = {5}, pages = {585-592}, pmid = {38775138}, issn = {1473-6551}, mesh = {*Amyotrophic Lateral Sclerosis/immunology/therapy/genetics ; Humans ; *Neuroinflammatory Diseases/immunology ; Animals ; Immunity, Innate/immunology ; Inflammation/immunology ; }, abstract = {PURPOSE OF REVIEW: Neuroinflammation appears to be an important pathogenic process in amyotrophic lateral sclerosis (ALS). Dysfunction of central immune pathways, including activation of microglia and astrocytes, and peripherally derived immune cells, initiate noncell autonomous inflammatory mechanisms leading to degeneration. Cell autonomous pathways linked to ALS genetic mutations have been recently identified as contributing mechanism for neurodegeneration. The current review provides insights into the pathogenic importance of central and peripheral inflammatory processes in ALS pathogenesis and appraises their potential as therapeutic targets.

RECENT FINDINGS: ALS is a multistep process mediated by a complex interaction of genetic, epigenetic, and environmental factors. Noncell autonomous inflammatory pathways contribute to neurodegeneration in ALS. Activation of microglia and astrocytes, along with central nervous system infiltration of peripherally derived pro-inflammatory innate (NK-cells/monocytes) and adaptive (cell-mediated/humoral) immune cells, are characteristic of ALS. Dysfunction of regulatory T-cells, elevation of pro-inflammatory cytokines and dysbiosis of gut microbiome towards a pro-inflammatory phenotype, have been reported as pathogenic mechanisms in ALS.

SUMMARY: Dysregulation of adaptive and innate immunity is pathogenic in ALS, being associated with greater disease burden, more rapid disease course and reduced survival. Strategies aimed at modulating the pro-inflammatory immune components could be of therapeutic utility.}, } @article {pmid38775034, year = {2024}, author = {Brooks, BR}, title = {Letter to the Editor: Glycemic Index/Load Effect on Amyotrophic Lateral Sclerosis Progression: Potential Interaction with Riluzole.}, journal = {Annals of neurology}, volume = {96}, number = {1}, pages = {208}, doi = {10.1002/ana.26970}, pmid = {38775034}, issn = {1531-8249}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy ; *Riluzole/therapeutic use ; *Disease Progression ; *Glycemic Index/drug effects ; Neuroprotective Agents/therapeutic use ; Blood Glucose/metabolism/drug effects ; }, } @article {pmid38774156, year = {2024}, author = {Canella, C and Braun, C and Witt, CM}, title = {Developing a digital mind body medicine supportive care intervention for people with amyotrophic lateral sclerosis using stakeholder engagement and design thinking.}, journal = {Digital health}, volume = {10}, number = {}, pages = {20552076241255928}, pmid = {38774156}, issn = {2055-2076}, abstract = {BACKGROUND: Amyotrophic lateral sclerosis disease (ALS) is also called the disease of a thousand farewells. Consequently, it is important to offer supportive care interventions that can be applied continuously during the whole course of the disease. People with ALS are interested in complementary and integrative medicine. Due to ALS' progressive nature, digital solutions might be most feasible and accessible for people with ALS in the long-term.

OBJECTIVES: In our study, we explored with stakeholders which digital complementary and integrative medicine interventions and formats are considered as supportive for people with ALS, and which settings are needed by the people with ALS to incorporate the interventions in everyday life.

METHODS: We used a participatory research approach and conducted a stakeholder engagement process, applying a design thinking process with qualitative research methods (interviews, workshops).

RESULTS: Due to the unpredictable course of the disease on their loss of abilities, people with ALS welcome online settings because they are accessible and easy to implement in their daily life. Stakeholders considered the following implementation factors for a complementary and integrative medicine intervention as essential: short-term realization of planned interventions, short duration of interventions, and user-friendliness in terms of accessibility and applicability. Concerning the complementary and integrative medicine interventions, the people with ALS preferred mind body medicine interventions, such as breathing, mindfulness and relaxation exercises.

CONCLUSIONS: Short-term treatment intervals and short online mind body medicine interventions align with the needs of people with ALS. The complementary and integrative medicine interventions as well as the digital infrastructure must meet the special accessibility and applicability needs of people with ALS.}, } @article {pmid38772930, year = {2024}, author = {Kherbek, H and Itoh, CY and Daley, C and Eggers, SD and Hinson, S and Sarker, P and Staff, NP and Pittock, SJ and Dubey, D}, title = {Clinical and serological insights into paraneoplastic brachial amyotrophic diplegia.}, journal = {Journal of neurology}, volume = {271}, number = {7}, pages = {4620-4627}, pmid = {38772930}, issn = {1432-1459}, support = {238183//State of Minnesota's David J. Tomassoni ALS Research Grant Program/ ; }, mesh = {Humans ; Male ; Middle Aged ; Retrospective Studies ; Aged ; Female ; *Paraneoplastic Syndromes, Nervous System/immunology/diagnosis/blood ; Adult ; Autoantibodies/blood ; Brachial Plexus Neuropathies/etiology/diagnosis/physiopathology ; Carrier Proteins ; }, abstract = {BACKGROUND: Brachial amyotrophic diplegia (BAD) is typically linked to a neurodegenerative etiology such as amyotrophic lateral sclerosis (ALS). Clinical and serological characterizations of paraneoplastic neurologic syndromes resembling BAD are limited.

METHODS: A retrospective chart review of patients with BAD-like presentations was conducted. Clinical/paraclinical features of paraneoplastic BAD and neurodegenerative BAD cases were compared.

RESULTS: Between 2017 and 2023, 13 cases of BAD were identified, of these 10 were neurodegenerative BAD (ALS variant), and 3 cases associated with paraneoplastic autoimmunity. An additional paraneoplastic BAD case diagnosed in 2005 was included. LUZP4-IgG was detected in all four paraneoplastic cases, with coexisting KLHL11-IgG in three cases and ANNA1 (anti-Hu)-IgG in one case. Out of the four paraneoplastic cases, two patients had seminoma, while the remaining two had limited cancer investigation. Three patients exhibited bi-brachial weakness as the initial symptom before the onset of brainstem symptoms or seizures. Compared to BAD patients with a neurodegenerative etiology, a higher proportion of paraneoplastic cases had ataxia (75% vs 0%, p = 0.011). Other clinical features only detected in the paraneoplastic BAD group were vertigo (n = 2), hearing loss (n = 2) and ophthalmoplegia (n = 2). Electrodiagnostic studies in these patients revealed cervical myotome involvement, supportive of motor neuronopathy. All paraneoplastic cases but none of the neurodegenerative BAD cases exhibited inflammatory cerebrospinal fluid (CSF) findings (lymphocytic pleocytosis and/or supernumerary oligoclonal bands; p = 0.067). Despite the administration of immunotherapy and/or cancer treatment, none of the paraneoplastic patients reported clinical improvement.

DISCUSSION: BAD or bi-brachial neurogenic weakness is a rare phenotypic presentation associated with paraneoplastic autoimmunity. Co-existing features of brainstem dysfunction or cerebellar ataxia should prompt further paraneoplastic evaluation. Common serological and cancer associations among these cases include LUZP4-IgG and KLHL11-IgG, along with testicular germ cell tumors, respectively.}, } @article {pmid38772669, year = {2024}, author = {Martínez Bilesio, AR and Puig-Castellví, F and Tauler, R and Sciara, M and Fay, F and Rasia, RM and Burdisso, P and García-Reiriz, AG}, title = {Multivariate curve resolution-based data fusion approaches applied in [1]H NMR metabolomic analysis of healthy cohorts.}, journal = {Analytica chimica acta}, volume = {1309}, number = {}, pages = {342689}, doi = {10.1016/j.aca.2024.342689}, pmid = {38772669}, issn = {1873-4324}, mesh = {Humans ; *Metabolomics/methods ; Male ; Female ; Multivariate Analysis ; Healthy Volunteers ; Adult ; Proton Magnetic Resonance Spectroscopy ; Cohort Studies ; Middle Aged ; Least-Squares Analysis ; Young Adult ; }, abstract = {BACKGROUND: Metabolomics plays a critical role in deciphering metabolic alterations within individuals, demanding the use of sophisticated analytical methodologies to navigate its intricate complexity. While many studies focus on single biofluid types, simultaneous analysis of multiple matrices enhances understanding of complex biological mechanisms. Consequently, the development of data fusion methods enabling multiblock analysis becomes essential for comprehensive insights into metabolic dynamics.

RESULTS: This study introduces a novel guideline for jointly analyzing diverse metabolomic datasets (serum, urine, metadata) with a focus on metabolic differences between groups within a healthy cohort. The guideline presents two fusion strategies, 'Low-Level data fusion' (LLDF) and 'Mid-Level data fusion' (MLDF), employing a sequential application of Multivariate Curve Resolution with Alternating Least Squares (MCR-ALS), linking the outcomes of successive analyses. MCR-ALS is a versatile method for analyzing mixed data, adaptable at various stages of data processing-encompassing resonance integration, data compression, and exploratory analysis. The LLDF and MLDF strategies were applied to [1]H NMR spectral data extracted from urine and serum samples, coupled with biochemical metadata sourced from 145 healthy volunteers.

SIGNIFICANCE: Both methodologies effectively integrated and analysed multiblock datasets, unveiling the inherent data structure and variables associated with discernible factors among healthy cohorts. While both approaches successfully detected sex-related differences, the MLDF strategy uniquely revealed components linked to age. By applying this analysis, we aim to enhance the interpretation of intricate biological mechanisms and uncover variations that may not be easily discernible through individual data analysis.}, } @article {pmid38771698, year = {2024}, author = {Alarcan, H and Bruno, C and Emond, P and Raoul, C and Vourc'h, P and Corcia, P and Camu, W and Veyrune, JL and Garlanda, C and Locati, M and Juntas-Morales, R and Saker, S and Suehs, C and Masseguin, C and Kirby, J and Shaw, P and Malaspina, A and De Vos, J and Al-Chalabi, A and Leigh, PN and Tree, T and Bensimon, G and Blasco, H}, title = {Pharmacometabolomics applied to low-dose interleukin-2 treatment in amyotrophic lateral sclerosis.}, journal = {Annals of the New York Academy of Sciences}, volume = {1536}, number = {1}, pages = {82-91}, doi = {10.1111/nyas.15147}, pmid = {38771698}, issn = {1749-6632}, support = {//National Institute of Health and Medical Research/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/drug therapy/metabolism ; Humans ; *Interleukin-2/administration & dosage/metabolism ; *Metabolomics/methods ; *T-Lymphocytes, Regulatory/metabolism/drug effects/immunology ; Male ; Middle Aged ; Female ; Kynurenine/metabolism ; Aged ; Metabolome/drug effects ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a devastating motor neuron disease. The immunosuppressive functions of regulatory T lymphocytes (Tregs) are impaired in ALS, and correlate to disease progression. The phase 2a IMODALS trial reported an increase in Treg number in ALS patients following the administration of low-dose (ld) interleukin-2 (IL-2). We propose a pharmacometabolomics approach to decipher metabolic modifications occurring in patients treated with ld-IL-2 and its relationship with Treg response. Blood metabolomic profiles were determined on days D1, D64, and D85 from patients receiving 2 MIU of IL-2 (n = 12) and patients receiving a placebo (n = 12). We discriminated the three time points for the treatment group (average error rate of 42%). Among the important metabolites, kynurenine increased between D1 and D64, followed by a reduction at D85. The percentage increase of Treg number from D1 to D64, as predicted by the metabolome at D1, was highly correlated with the observed value. This study provided a proof of concept for metabolic characterization of the effect of ld-IL-2 in ALS. These data could present advances toward a personalized medicine approach and present pharmacometabolomics as a key tool to complement genomic and transcriptional data for drug characterization, leading to systems pharmacology.}, } @article {pmid38771230, year = {2024}, author = {Maccabeo, A and Salustro, E and Sanna, M and Garau, P and Maioli, MA and Coa, R and Puligheddu, M and Borghero, G}, title = {Scleroderma-Polymyositis Overlap Syndrome as a Potential Bulbar Amyotrophic Lateral Sclerosis Mimic.}, journal = {Journal of clinical neuromuscular disease}, volume = {25}, number = {4}, pages = {199-200}, doi = {10.1097/CND.0000000000000467}, pmid = {38771230}, issn = {1537-1611}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/complications/diagnosis ; Diagnosis, Differential ; *Polymyositis/complications ; Scleroderma, Systemic/complications ; }, } @article {pmid38770222, year = {2024}, author = {Lagrange, E and Loriot, MA and Chaudhary, NK and Schultz, P and Dirks, AC and Guissart, C and James, TY and Vernoux, JP and Camu, W and Tripathi, A and Spencer, PS}, title = {Corrected speciation and gyromitrin content of false morels linked to ALS patients with mostly slow-acetylator phenotypes.}, journal = {eNeurologicalSci}, volume = {35}, number = {}, pages = {100502}, pmid = {38770222}, issn = {2405-6502}, abstract = {A case-control study of sporadic amyotrophic lateral sclerosis (ALS) in a mountainous village in the French Alps discovered an association of cases with a history of eating wild fungi (false morels) collected locally and initially identified and erroneously reported as Gyromitra gigas. Specialist re-examination of dried specimens of the ALS-associated fungi demonstrated they were members of the G. esculenta group, namely G. venenata and G. esculenta, species that have been reported to contain substantially higher concentrations of gyromitrin than present in G. gigas. Gyromitrin is metabolized to monomethylhydrazine, which is responsible not only for the acute oral toxic and neurotoxic properties of false morels but also has genotoxic potential with proposed mechanistic relevance to the etiology of neurodegenerative disease. Most ALS patients had a slow- or intermediate-acetylator phenotype predicted by N-acetyltransferase-2 (NAT2) genotyping, which would increase the risk for neurotoxic and genotoxic effects of gyromitrin metabolites.}, } @article {pmid38769202, year = {2024}, author = {Benatar, M and Wuu, J and Huey, ED and McMillan, CT and Petersen, RC and Postuma, R and McHutchison, C and Dratch, L and Arias, JJ and Crawley, A and Houlden, H and McDermott, MP and Cai, X and Thakur, N and Boxer, A and Rosen, H and Boeve, BF and Dacks, P and Cosentino, S and Abrahams, S and Shneider, N and Lingor, P and Shefner, J and Andersen, PM and Al-Chalabi, A and Turner, MR and , }, title = {The Miami Framework for ALS and related neurodegenerative disorders: an integrated view of phenotype and biology.}, journal = {Nature reviews. Neurology}, volume = {20}, number = {6}, pages = {364-376}, pmid = {38769202}, issn = {1759-4766}, support = {U01 AG079850/AG/NIA NIH HHS/United States ; R01 MH120794/MH/NIMH NIH HHS/United States ; K01 AG057796/AG/NIA NIH HHS/United States ; U54 NS092091/NS/NINDS NIH HHS/United States ; R01 NS105479/NS/NINDS NIH HHS/United States ; R01 AG062268/AG/NIA NIH HHS/United States ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/diagnosis/metabolism/pathology ; *Phenotype ; *Frontotemporal Dementia/genetics/diagnosis/metabolism ; Neurodegenerative Diseases/diagnosis/metabolism/genetics ; Biomarkers/metabolism ; }, abstract = {Increasing appreciation of the phenotypic and biological overlap between amyotrophic lateral sclerosis (ALS) and frontotemporal dementia, alongside evolving biomarker evidence for a pre-symptomatic stage of disease and observations that this stage of disease might not always be clinically silent, is challenging traditional views of these disorders. These advances have highlighted the need to adapt ingrained notions of these clinical syndromes to include both the full phenotypic continuum - from clinically silent, to prodromal, to clinically manifest - and the expanded phenotypic spectrum that includes ALS, frontotemporal dementia and some movement disorders. The updated clinical paradigms should also align with our understanding of the biology of these disorders, reflected in measurable biomarkers. The Miami Framework, emerging from discussions at the Second International Pre-Symptomatic ALS Workshop in Miami (February 2023; a full list of attendees and their affiliations appears in the Supplementary Information) proposes a classification system built on: first, three parallel phenotypic axes - motor neuron, frontotemporal and extrapyramidal - rather than the unitary approach of combining all phenotypic elements into a single clinical entity; and second, biomarkers that reflect different aspects of the underlying pathology and biology of neurodegeneration. This framework decouples clinical syndromes from biomarker evidence of disease and builds on experiences from other neurodegenerative diseases to offer a unified approach to specifying the pleiotropic clinical manifestations of disease and describing the trajectory of emergent biomarkers.}, } @article {pmid38768217, year = {2024}, author = {Petrauskas, A and Fortunati, DL and Kandi, AR and Pothapragada, SS and Agrawal, K and Singh, A and Huelsmeier, J and Hillebrand, J and Brown, G and Chaturvedi, D and Lee, J and Lim, C and Auburger, G and VijayRaghavan, K and Ramaswami, M and Bakthavachalu, B}, title = {Structured and disordered regions of Ataxin-2 contribute differently to the specificity and efficiency of mRNP granule formation.}, journal = {PLoS genetics}, volume = {20}, number = {5}, pages = {e1011251}, pmid = {38768217}, issn = {1553-7404}, support = {/WT_/Wellcome Trust/United Kingdom ; }, mesh = {*Ataxin-2/genetics/metabolism ; Animals ; Humans ; *Ribonucleoproteins/genetics/metabolism ; *Drosophila Proteins/genetics/metabolism ; *Drosophila melanogaster/genetics/metabolism ; *RNA, Messenger/genetics/metabolism ; Poly(A)-Binding Proteins/metabolism/genetics ; Animals, Genetically Modified ; Cytoplasmic Granules/metabolism/genetics ; Amyotrophic Lateral Sclerosis/genetics/metabolism ; Protein Biosynthesis ; RNA-Binding Proteins/genetics/metabolism ; Intrinsically Disordered Proteins/genetics/metabolism ; Nerve Tissue Proteins/genetics/metabolism ; DNA-Binding Proteins ; }, abstract = {Ataxin-2 (ATXN2) is a gene implicated in spinocerebellar ataxia type II (SCA2), amyotrophic lateral sclerosis (ALS) and Parkinsonism. The encoded protein is a therapeutic target for ALS and related conditions. ATXN2 (or Atx2 in insects) can function in translational activation, translational repression, mRNA stability and in the assembly of mRNP-granules, a process mediated by intrinsically disordered regions (IDRs). Previous work has shown that the LSm (Like-Sm) domain of Atx2, which can help stimulate mRNA translation, antagonizes mRNP-granule assembly. Here we advance these findings through a series of experiments on Drosophila and human Ataxin-2 proteins. Results of Targets of RNA Binding Proteins Identified by Editing (TRIBE), co-localization and immunoprecipitation experiments indicate that a polyA-binding protein (PABP) interacting, PAM2 motif of Ataxin-2 may be a major determinant of the mRNA and protein content of Ataxin-2 mRNP granules. Experiments with transgenic Drosophila indicate that while the Atx2-LSm domain may protect against neurodegeneration, structured PAM2- and unstructured IDR- interactions both support Atx2-induced cytotoxicity. Taken together, the data lead to a proposal for how Ataxin-2 interactions are remodelled during translational control and how structured and non-structured interactions contribute differently to the specificity and efficiency of RNP granule condensation as well as to neurodegeneration.}, } @article {pmid38767564, year = {2024}, author = {Natung, T and Pandey, I and Nongrum, B and Sekhose, EK}, title = {Comparison of Hill-RBF 3.0 with Barrett Universal II, SRK/T, Hoffer Q, Haigis, and Holladay 1 to predict the accuracy of post-cataract surgery refractive outcomes in Indian eyes.}, journal = {Indian journal of ophthalmology}, volume = {72}, number = {9}, pages = {1261-1266}, pmid = {38767564}, issn = {1998-3689}, mesh = {Humans ; Prospective Studies ; Male ; Female ; India/epidemiology ; *Refraction, Ocular/physiology ; Middle Aged ; *Visual Acuity/physiology ; Aged ; Follow-Up Studies ; Lenses, Intraocular ; Phacoemulsification ; Postoperative Period ; Lens Implantation, Intraocular ; Refractive Errors/physiopathology/diagnosis/epidemiology ; }, abstract = {PURPOSE: To compare Hill-RBF 3.0 with Barrett Universal II (BU II), SRK/T, Hoffer Q, Haigis, and Holladay 1 in predicting the accuracy of post-cataract surgery refractive outcomes in Indian eyes.

METHODS: In this prospective, comparative, observational study, consecutive patients with uncomplicated age-related cataracts undergoing uneventful phacoemulsification with posterior chamber intraocular lens (IOL) implantation were included. The mean absolute errors (MAEs) and median absolute errors were used to determine the accuracy of predicted postoperative target refractions.

RESULTS: A total of 219 eyes of 173 patients were enrolled. Based on the axial lengths (AL), the patients were classified into: AL <22 mm (short), 22-24.5 mm (normal), and >24.5 mm (long). BU II exhibited the lowest MAE for normal ALs (0.2683 ± 0.2790 D) as well as for the entire population (0.2764 ± 0.2764 D). For the short ALs, Hill RBF 3.0 exhibited the lowest MAE (0.3268 ± 0.3268 D), while for the long ALs, SRK/T showed the lowest MAE (0.2823 ± 0.2642 D). BU II exhibited the highest percentage of eyes of 57.5%, 95.4%, and 98.6% within ±0.25, ±0.75, and ±1.0 D of postoperative target refractions respectively, whereas Hill RBF 3.0 had the highest percentages of eyes (88.1%) within ±0.5 D of postoperative target refraction.

CONCLUSION: Hill-RBF 3.0 exhibited the least MAE for patients with short ALs, while BU II showed the least MAE for normal ALs as well as for the entire population and SRK/T for long ALs. This study is likely to aid surgeons in selecting the most appropriate IOL power formula, which thereby improves the refractive outcomes with utmost accuracy.}, } @article {pmid38767482, year = {2025}, author = {Martinelli, I and Mandrioli, J and Ghezzi, A and Zucchi, E and Gianferrari, G and Simonini, C and Cavallieri, F and Valzania, F}, title = {Multifaceted superoxide dismutase 1 expression in amyotrophic lateral sclerosis patients: a rare occurrence?.}, journal = {Neural regeneration research}, volume = {20}, number = {1}, pages = {130-138}, pmid = {38767482}, issn = {1673-5374}, abstract = {Amyotrophic lateral sclerosis (ALS) is a neuromuscular condition resulting from the progressive degeneration of motor neurons in the cortex, brainstem, and spinal cord. While the typical clinical phenotype of ALS involves both upper and lower motor neurons, human and animal studies over the years have highlighted the potential spread to other motor and non-motor regions, expanding the phenotype of ALS. Although superoxide dismutase 1 (SOD1) mutations represent a minority of ALS cases, the SOD1 gene remains a milestone in ALS research as it represents the first genetic target for personalized therapies. Despite numerous single case reports or case series exhibiting extramotor symptoms in patients with ALS mutations in SOD1 (SOD1-ALS), no studies have comprehensively explored the full spectrum of extramotor neurological manifestations in this subpopulation. In this narrative review, we analyze and discuss the available literature on extrapyramidal and non-motor features during SOD1-ALS. The multifaceted expression of SOD1 could deepen our understanding of the pathogenic mechanisms, pointing towards a multidisciplinary approach for affected patients in light of new therapeutic strategies for SOD1-ALS.}, } @article {pmid38767073, year = {2024}, author = {Napoletano, G and Circosta, F and Basile, G}, title = {Access to medically-assisted procreation: the withdrawal of paternal consent in the maze of law n. 40/2004.}, journal = {La Clinica terapeutica}, volume = {175}, number = {3}, pages = {163-167}, doi = {10.7417/CT.2024.5057}, pmid = {38767073}, issn = {1972-6007}, mesh = {Humans ; *Reproductive Techniques, Assisted/legislation & jurisprudence/ethics ; Italy ; Female ; Male ; Health Services Accessibility/legislation & jurisprudence ; Cryopreservation ; Parental Consent/legislation & jurisprudence ; Informed Consent/legislation & jurisprudence ; }, abstract = {The law (No.40/2004) stipulates that consent to Medically Assisted Procreation (MAP) remains irrevocable post ovum fertilization. Cryo-preservation introduces complexities, enabling embryo implantation requests after a couple's separation and the dissolution of the original parenthood plan. Constitutional Court Ruling No.161 in 2023 affirmed that the prohibition of revoking consent to MAP aligns with the Italian Constitution and the jurisprudence of the European Court of Human Rights. This delicate equilibrium of conflicting interests upholds human freedom, allowing consent revocation prior to ovocyte fertilization. Permitting revocation until implantation could inflict more significant harm: the infertile woman can in fact miss the opportunity to become a mother, impacting her psychophysical well-being and freedom of self-determination. Moreover, the embryo loses the chance to live, remaining in cryopreservation, which violates its dignity. Addressing this issue requires thorough communication by medical profession-als to inform couples about the limitations on consent revocation. An element of objectivity in terms of standards and evidence-based guidelines, from which norms must originate, is of utmost importance. Relying on broadly shared rules, especially at the international level, is vital in light of the unremitting scientific advances in MAP, as in other areas of medicine, which will open up new opportunities for which current legal/regulatory frameworks are inadequate.}, } @article {pmid38766825, year = {2025}, author = {Tedeschi, V and Sapienza, S and Ciancio, R and Canzoniero, LMT and Pannaccione, A and Secondo, A}, title = {Lysosomal Channels as New Molecular Targets in the Pharmacological Therapy of Neurodegenerative Diseases via Autophagy Regulation.}, journal = {Current neuropharmacology}, volume = {23}, number = {4}, pages = {375-383}, pmid = {38766825}, issn = {1875-6190}, support = {PE0000006//National Recovery and Resilience Plan (NRRP), project MNESYS/ ; }, mesh = {Humans ; *Autophagy/drug effects/physiology ; Animals ; *Neurodegenerative Diseases/drug therapy/metabolism ; *Lysosomes/metabolism/drug effects ; *Transient Receptor Potential Channels/metabolism ; *Calcium Channels/metabolism ; Molecular Targeted Therapy ; }, abstract = {Besides controlling several organellar functions, lysosomal channels also guide the catabolic "self-eating" process named autophagy, which is mainly involved in protein and organelle quality control. Neuronal cells are particularly sensitive to the rate of autophagic flux either under physiological conditions or during the degenerative process. Accordingly, neurodegeneration occurring in Parkinson's (PD), Alzheimer's (AD), and Huntington's Diseases (HD), and Amyotrophic Lateral Sclerosis (ALS) as well as Lysosomal Storage Diseases (LSD) is partially due to defective autophagy and accumulation of toxic aggregates. In this regard, dysfunction of lysosomal ionic homeostasis has been identified as a putative cause of aberrant autophagy. From a therapeutic perspective, Transient Receptor Potential Channel Mucolipin 1 (TRPML1) and Two-Pore Channel isoform 2 (TPC2), regulating lysosomal homeostasis, are now considered promising druggable targets in neurodegenerative diseases. Compelling evidence suggests that pharmacological modulation of TRPML1 and TPC2 may rescue the pathological phenotype associated with autophagy dysfunction in AD, PD, HD, ALS, and LSD. Although pharmacological repurposing has identified several already used drugs with the ability to modulate TPC2, and several tools are already available for the modulation of TRPML1, many efforts are necessary to design and test new entities with much higher specificity in order to reduce dysfunctional autophagy during neurodegeneration.}, } @article {pmid38765269, year = {2024}, author = {Cheng, J and Niu, X and Li, H and Yang, Q and Du, K}, title = {Evaluation of the therapeutic effects of rehabilitation therapy on patients with amyotrophic lateral sclerosis-a meta-analysis.}, journal = {Frontiers in neurology}, volume = {15}, number = {}, pages = {1389146}, pmid = {38765269}, issn = {1664-2295}, abstract = {OBJECTIVE: To investigate the effect of rehabilitation therapy on the global function, respiratory function, and quality of life in patients with amyotrophic lateral sclerosis (ALS).

METHODS: PubMed, Web of Science, and The National Library of Medicine (NLM) were systematically searched and the search period was between the date of database establishment and December 31, 2023. The outcome measures finally analyzed included the ALS functional rating scale/revised (ALSFRS/ALSFRS-R), forced vital capacity percentage predicted (FVC%), fatigue severity scale (FSS), and maximal expiratory pressure (MEP).

RESULTS: A total of 13 randomized controlled trials (RCTs) were included, and 5 outcome measures were pooled and analyzed. A total of 657 patients with ALS were enrolled, with 299 in the experimental group (rehabilitation therapy, such as resistance training, endurance training, aerobic training, respiratory muscle training, and standard rehabilitation therapy) and 358 in the control group (conventional interventions, such as simple joint movements or daily stretching). The ALSFRS scores were better in the experimental group than in the control group at 0-4 months (MD = 3.36, 95% CI: 0.82, 5.91, Z = 2.59, p = 0.009) and at 5-8 months (MD = 5.00, 95% CI: -2.42, 7.58, Z = 3.80, p < 0.001). Moreover, the ALSFRS-R scores of the experimental group was better than that of the control group at 5-8 months (MD = 2.83, 95% CI: 1.21, 4.45, Z = 3.42, p < 0.001) and 9-12 months (MD = 1.87, 95% CI: -0.37, 4.11, Z = 1.63, p = 0.10). It was also found that the MEP value of the experimental group was significantly better than that of the control group after intervention (MD = 18.49, 95% CI: 1.47, 35.50, Z = 2.13, p = 0.03). However, there were no significant differences in FVC% value and FSS scores at 0-5 months and 6-12 months between the two groups.

CONCLUSION: Rehabilitation therapy is helpful in improving the short-, medium-, and long-term global function score of patients with ALS, with positive effects on respiratory function.}, } @article {pmid38765264, year = {2024}, author = {Colognesi, M and Shkodra, A and Gabbia, D and Kawamata, H and Manfredi, PL and Manfredi, G and De Martin, S}, title = {Sex-dependent effects of the uncompetitive N-methyl-D-aspartate receptor antagonist REL-1017 in G93A-SOD1 amyotrophic lateral sclerosis mice.}, journal = {Frontiers in neurology}, volume = {15}, number = {}, pages = {1384829}, pmid = {38765264}, issn = {1664-2295}, support = {R35 NS122209/NS/NINDS NIH HHS/United States ; }, abstract = {INTRODUCTION: The pathogenesis of amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease caused by the demise of motor neurons has been linked to excitotoxicity caused by excessive calcium influx via N-methyl-D-aspartate receptors (NMDARs), suggesting that uncompetitive NMDAR antagonism could be a strategy to attenuate motor neuron degeneration. REL-1017, the dextro-isomer of racemic methadone, is a low-affinity uncompetitive NMDAR antagonist. Importantly, in humans REL-1017 has shown excellent tolerability in clinical trials for major depression.

METHODS: Here, we tested if REL-1017 improves the disease phenotypes in the G93A SOD1 mouse, a well-established model of familial ALS, by examining survival and motor functions, as well as the expression of genes and proteins involved in neuroplasticity.

RESULTS: We found a sex-dependent effect of REL-1017 in G93A SOD1 mice. A delay of ALS symptom onset, assessed as 10%-decrease of body weight (p < 0.01 vs. control untreated mice) and an extension of lifespan (p < 0.001 vs. control untreated mice) was observed in male G93A SOD1 mice. Female G93A SOD1 mice treated with REL-1017 showed an improvement of muscle strength (p < 0.01 vs. control untreated mice). Both males and females treated with REL-1017 showed a decrease in hind limb clasping. Sex-dependent effects of REL-1017 were also detected in molecular markers of neuronal plasticity (PSD95 and SYN1) in the spinal cord and in the GluN1 NMDAR subunit in quadricep muscles.

CONCLUSION: In conclusion, this study provides preclinical in vivo evidence supporting the clinical evaluation of REL-1017 in ALS.}, } @article {pmid38765173, year = {2024}, author = {Souayah, N and Chen, H and Chong, ZZ and Patel, T and Pahwa, A and Menkes, DL and Cunningham, T}, title = {Novel strategy: Identifying new markers for demyelination in diabetic distal symmetrical polyneuropathy.}, journal = {Heliyon}, volume = {10}, number = {9}, pages = {e30419}, pmid = {38765173}, issn = {2405-8440}, abstract = {OBJECTIVE: To develop a novel strategy for identifying acquired demyelination in diabetic distal symmetrical polyneuropathy (DSP).

BACKGROUND: Motor nerve conduction velocity (CV) slowing in diabetic DSP exceeds expectations for pure axonal loss thus implicating superimposed acquired demyelination.

METHODS: After establishing demyelination confidence intervals by regression analysis of nerve conduction data from chronic inflammatory demyelinating polyneuropathy (CIDP), we prospectively studied CV slowing in 90 diabetic DSP patients with and without at least one motor nerve exhibiting CV slowing (groups A and B) into the demyelination range by American Academy of Neurology (AAN) criteria respectively and 95 amyotrophic lateral sclerosis (ALS) patients. Simultaneously, secretory phospholipase A2 (sPLA2) activity was assessed in both diabetic groups and 46 healthy controls.

RESULTS: No ALS patient exhibited CV slowing in more than two motor nerves based on AAN criteria or the confidence intervals. Group A demonstrated a significantly higher percentage of patients as compared to group B fulfilling the above criteria, with an additional criterion of at least one motor nerve exhibiting CV slowing in the demyelinating range and a corresponding F response in the demyelinating range by AAN criteria (70.3 % vs. 1.9 %; p < 0.0001). Urine sPLA2 activity was increased significantly in diabetic groups as compared to healthy controls (942.9 ± 978.0 vs. 591.6 ± 390.2 pmol/min/ml, p < 0.05), and in group A compared to Group B (1328.3 ± 1274.2 vs. 673.8 ± 576.9 pmol/min/ml, p < 0.01). More patients with elevated sPLA2 activity and more than 2 motor nerves with CV slowing in the AAN or the confidence intervals were identified in group A as compared to group B (35.1 % vs. 5.7 %, p < 0.001). Furthermore, 13.5 % of patients in diabetic DSP Group A, and no patients in diabetic DSP Group B, fulfilled an additional criterion of more than one motor nerve with CV slowing into the demyelinating range with its corresponding F response into the demyelinating range by AAN criteria.

CONCLUSION: A combination of regression analysis of electrodiagnostic data and a urine biological marker of systemic inflammation identifies a subgroup of diabetic DSP with superimposed acquired demyelination that may respond favorably to immunomodulatory therapy.}, } @article {pmid38763702, year = {2024}, author = {Dorrity, TJ and Shin, H and Gertie, JA and Chung, H}, title = {The Sixth Sense: Self-nucleic acid sensing in the brain.}, journal = {Advances in immunology}, volume = {161}, number = {}, pages = {53-83}, pmid = {38763702}, issn = {1557-8445}, support = {R01 AR050026/AR/NIAMS NIH HHS/United States ; R01 NS127802/NS/NINDS NIH HHS/United States ; T32 AR076953/AR/NIAMS NIH HHS/United States ; T32 GM145440/GM/NIGMS NIH HHS/United States ; }, mesh = {Humans ; *Brain/metabolism/immunology ; Animals ; *Receptors, Pattern Recognition/metabolism ; *Immunity, Innate ; *Nucleic Acids/immunology/metabolism ; Homeostasis ; Signal Transduction ; }, abstract = {Our innate immune system uses pattern recognition receptors (PRRs) as a first line of defense to detect microbial ligands and initiate an immune response. Viral nucleic acids are key ligands for the activation of many PRRs and the induction of downstream inflammatory and antiviral effects. Initially it was thought that endogenous (self) nucleic acids rarely activated these PRRs, however emerging evidence indicates that endogenous nucleic acids are able to activate host PRRs in homeostasis and disease. In fact, many regulatory mechanisms are in place to finely control and regulate sensing of self-nucleic acids by PRRs. Sensing of self-nucleic acids is particularly important in the brain, as perturbations to nucleic acid sensing commonly leads to neuropathology. This review will highlight the role of nucleic acid sensors in the brain, both in disease and homeostasis. We also indicate the source of endogenous stimulatory nucleic acids where known and summarize future directions for the study of this growing field.}, } @article {pmid38762759, year = {2024}, author = {Wang, Z and Xiong, S and Wu, Z and Wang, X and Gong, Y and Zhu, WG and Xu, X}, title = {VCP/p97 UFMylation stabilizes BECN1 and facilitates the initiation of autophagy.}, journal = {Autophagy}, volume = {20}, number = {9}, pages = {2041-2054}, pmid = {38762759}, issn = {1554-8635}, mesh = {*Autophagy/physiology/genetics ; Humans ; *Valosin Containing Protein/metabolism/genetics ; *Beclin-1/metabolism ; *Ubiquitination ; Ataxin-3/metabolism/genetics ; Ubiquitin-Protein Ligases/metabolism ; HeLa Cells ; Phosphatidylinositol 3-Kinases/metabolism ; Protein Stability ; HEK293 Cells ; Intracellular Signaling Peptides and Proteins ; }, abstract = {Macroautophagy/autophagy is essential for the degradation and recycling of cytoplasmic materials. The initiation of this process is determined by phosphatidylinositol-3-kinase (PtdIns3K) complex, which is regulated by factor BECN1 (beclin 1). UFMylation is a novel ubiquitin-like modification that has been demonstrated to modulate several cellular activities. However, the role of UFMylation in regulating autophagy has not been fully elucidated. Here, we found that VCP/p97 is UFMylated on K109 by the E3 UFL1 (UFM1 specific ligase 1) and this modification promotes BECN1 stabilization and assembly of the PtdIns3K complex, suggesting a role for VCP/p97 UFMylation in autophagy initiation. Mechanistically, VCP/p97 UFMylation stabilizes BECN1 through ATXN3 (ataxin 3)-mediated deubiquitination. As a key component of the PtdIns3K complex, stabilized BECN1 facilitates assembly of this complex. Re-expression of VCP/p97, but not the UFMylation-defective mutant, rescued the VCP/p97 depletion-induced increase in MAP1LC3B/LC3B protein expression. We also showed that several pathogenic VCP/p97 mutations identified in a variety of neurological disorders and cancers were associated with reduced UFMylation, thus implicating VCP/p97 UFMylation as a potential therapeutic target for these diseases. Abbreviation: ATG14:autophagy related 14; Baf A1:bafilomycin A1;CMT2Y: Charcot-Marie-Toothdisease, axonal, 2Y; CYB5R3: cytochromeb5 reductase 3; DDRGK1: DDRGK domain containing 1; DMEM:Dulbecco'smodified Eagle's medium;ER:endoplasmic reticulum; FBS:fetalbovine serum;FTDALS6:frontotemporaldementia and/or amyotrophic lateral sclerosis 6; IBMPFD1:inclusion bodymyopathy with early-onset Paget disease with or withoutfrontotemporal dementia 1; LC-MS/MS:liquid chromatography tandem mass spectrometry; MAP1LC3B/LC3B:microtubule associated protein 1 light chain 3 beta; MS: massspectrometry; NPLOC4: NPL4 homolog, ubiquitin recognition factor;PIK3C3: phosphatidylinositol 3-kinase catalytic subunit type 3;PIK3R4: phosphoinositide-3-kinase regulatory subunit 4; PtdIns3K:phosphatidylinositol 3-kinase; RPL26: ribosomal protein L26; RPN1:ribophorin I; SQSTM1/p62: sequestosome 1; UBA5: ubiquitin likemodifier activating enzyme 5; UFC1: ubiquitin-fold modifierconjugating enzyme 1; UFD1: ubiquitin recognition factor in ERassociated degradation 1; UFL1: UFM1 specific ligase 1; UFM1:ubiquitin fold modifier 1; UFSP2: UFM1 specific peptidase 2; UVRAG:UV radiation resistance associated; VCP/p97: valosin containingprotein; WT: wild-type.}, } @article {pmid38762656, year = {2024}, author = {Li, Z and Kang, H}, title = {Efficacy of non-pharmacological interventions for individuals with amyotrophic lateral sclerosis: systematic review and network meta-analysis of randomized control trials.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {11365}, pmid = {38762656}, issn = {2045-2322}, mesh = {*Amyotrophic Lateral Sclerosis/therapy/physiopathology ; Humans ; *Randomized Controlled Trials as Topic ; *Quality of Life ; Exercise Therapy/methods ; Treatment Outcome ; Muscle Strength ; }, abstract = {This network meta-analysis (NMA) aimed to compare the efficacy of five non-pharmacological interventions, including exercise intervention (EI), nutritional intervention (NI), respiratory intervention (RI), psychological intervention (PSI), and integrated physical intervention (IPI), on functional status, quality of life, muscle strength, pulmonary function, and safety in patients with amyotrophic lateral sclerosis (ALS). We searched nine databases, PubMed, Cochrane, Embase, Scopus, Web of Science, CNKI, CBM, WFPD, and CSTJ, for randomized controlled trials of ALS patients. The primary outcome was the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) score. Secondary outcomes were the McGill Quality of Life Questionnaire (McGill-QoL), Medical Research Council (MRC)-sum score, Forced Vital Capacity (FVC), and Fatigue Severity Scale (FSS) score. This NMA was conducted using random-effect models to calculate the standard mean difference (SMD) and 95% confidence interval (CI). All types of supplemental interventions had some benefit for patients with ALS. EI had a beneficial effect on the ALSFRS-R score (SMD: 1.01; 95% CI 0.50-1.51), FVC (SMD: 0.78; 95% CI 0.02-1.55), McGill-QoL (SMD: 0.71 95% CI 0.33-1.08), and MRC (SMD: 1.11; 95% CI 0.08-2.14). RI had a beneficial effect on the ALSFRS-R score (SMD: 0.83 95% CI 0.12-1.55). IPI had a beneficial effect on the ALSFRS-R score (SMD: 0.65 95% CI 0.06-1.24). NI had a beneficial effect on the McGill-QoL (SMD: 0.63 95% CI 0.02-1.23). The current study findings support a multimodal intervention strategy with an emphasis on EI for slowing disease progression in patients with ALS.}, } @article {pmid38762243, year = {2024}, author = {Ponzini, E}, title = {Tear biomarkers.}, journal = {Advances in clinical chemistry}, volume = {120}, number = {}, pages = {69-115}, doi = {10.1016/bs.acc.2024.03.002}, pmid = {38762243}, issn = {2162-9471}, mesh = {Humans ; *Tears/metabolism/chemistry ; *Biomarkers/analysis/metabolism ; Eye Diseases/diagnosis/metabolism ; }, abstract = {An extensive exploration of lacrimal fluid molecular biomarkers in understanding and diagnosing a spectrum of ocular and systemic diseases is presented. The chapter provides an overview of lacrimal fluid composition, elucidating the roles of proteins, lipids, metabolites, and nucleic acids within the tear film. Pooled versus single-tear analysis is discussed to underline the benefits and challenges associated with both approaches, offering insights into optimal strategies for tear sample analysis. Subsequently, an in-depth analysis of tear collection methods is presented, with a focus on Schirmer's test strips and microcapillary tubes methods. Alternative tear collection techniques are also explored, shedding light on their applicability and advantages. Variability factors, including age, sex, and diurnal fluctuations, are examined in the context of their impact on tear biomarker analysis. The main body of the chapter is dedicated to discussing specific biomarkers associated with ocular discomfort and a wide array of ocular diseases. From dry eye disease and thyroid-associated ophthalmopathy to keratoconus, age-related macular degeneration, diabetic retinopathy, and glaucoma, the intricate relationship between molecular biomarkers and these conditions is thoroughly dissected. Expanding beyond ocular pathologies, the chapter explores the applicability of tear biomarkers in diagnosing systemic diseases such as multiple sclerosis, amyotrophic lateral sclerosis, Alzheimer's disease, Parkinson's disease, and cancer. This broader perspective underscores the potential of lacrimal fluid analysis in offering non-invasive diagnostic tools for conditions with far-reaching implications.}, } @article {pmid38761668, year = {2024}, author = {Silani, V}, title = {Continuity of treatment in ALS: Benefits and challenges of maintaining riluzole over the course of the disease.}, journal = {Journal of the neurological sciences}, volume = {461}, number = {}, pages = {123038}, doi = {10.1016/j.jns.2024.123038}, pmid = {38761668}, issn = {1878-5883}, mesh = {Humans ; *Riluzole/therapeutic use ; *Amyotrophic Lateral Sclerosis/drug therapy ; *Neuroprotective Agents/therapeutic use ; Male ; Female ; Middle Aged ; }, } @article {pmid38760965, year = {2024}, author = {Lee, SY and Yoo, SH and Cho, B and Kim, KH and Jang, MS and Shin, J and Hwang, I and Choi, SJ and Sung, JJ and Kim, MS}, title = {Burden and preparedness of care partners of people living with amyotrophic lateral sclerosis at home in Korea: A care partner survey.}, journal = {Muscle & nerve}, volume = {70}, number = {3}, pages = {306-315}, doi = {10.1002/mus.28115}, pmid = {38760965}, issn = {1097-4598}, support = {HC21C0115//Patient-Centered Clinical Research Coordinating Center(PACEN) funded by the Ministry of Health and Welfare, Republic of Korea/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy/psychology/nursing ; Male ; Republic of Korea/epidemiology ; Female ; *Caregivers/psychology ; Middle Aged ; Aged ; Adult ; Surveys and Questionnaires ; Depression/psychology/therapy/epidemiology ; Home Care Services ; Cost of Illness ; Tracheostomy ; Spouses/psychology ; Caregiver Burden/psychology ; }, abstract = {INTRODUCTION/AIMS: The care burden of people living with amyotrophic lateral sclerosis (pALS) increases with disease progression. This study aimed to investigate the home care status and preparedness of care partners of pALS (cALS) in Korea.

METHODS: An online survey was conducted with family care partners of patients diagnosed with ALS for over 1 year in 2022. The data collected included care time, depression evaluated using the patient health questionnaire-9 (PHQ-9), preparedness for caregiving scale (PCS), and caregiver competence scale (CCS). Results were compared based on whether the pALS underwent a tracheostomy or not.

RESULTS: Ninety-eight cALS of 98 pALS participated in the study, of whom 59 pALS had undergone tracheostomy. Among the cALS, 60.2% were spouses, and 34.7% were children. The cALS took care of the patients for 13 (8-20) hours/day (median, interquartile range [IQR]) on weekdays and 15 (10-24) h/day on weekends. Among the cALS, 91.8% were depressed, and 28.6% had severe depression. The median (IQR) PCS and CCS scores were low (11/32 (8-15) and 8/20 (8-11), respectively), and both were lower in those caring for patients without than with tracheostomy (p < .001 and p < .02, respectively). Most cALS (77.6%) wished to continue caring for their pALS at home.

DISCUSSION: Family care partners of pALS spend more than half of each day caring for patients and are often depressed. Most cALS preferred providing care at home, but felt ill-prepared. Designing home-based medical care is necessary for pALS to thrive at home.}, } @article {pmid38760935, year = {2024}, author = {Fiadeiro, MB and Diogo, JC and Silva, AA and Kim, YS and Cristóvão, AC}, title = {NADPH Oxidases in Neurodegenerative Disorders: Mechanisms and Therapeutic Opportunities.}, journal = {Antioxidants & redox signaling}, volume = {41}, number = {7-9}, pages = {522-541}, doi = {10.1089/ars.2023.0002}, pmid = {38760935}, issn = {1557-7716}, mesh = {Humans ; *Neurodegenerative Diseases/metabolism/drug therapy ; *NADPH Oxidases/metabolism/antagonists & inhibitors ; *Reactive Oxygen Species/metabolism ; Animals ; Oxidative Stress ; }, abstract = {Significance: The nicotinamide adenine dinucleotide phosphate oxidase (NOX) enzyme family, located in the central nervous system, is recognized as a source of reactive oxygen species (ROS) in the brain. Despite its importance in cellular processes, excessive ROS generation leads to cell death and is involved in the pathogenesis of neurodegenerative disorders. Recent advances: NOX enzymes contribute to the development of neurodegenerative diseases, such as Parkinson's disease (PD), Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), and stroke, highlighting their potential as targets for future therapeutic development. This review will discuss NOX's contribution and therapeutic targeting potential in neurodegenerative diseases, focusing on PD, AD, ALS, and stroke. Critical issues: Homeostatic and physiological levels of ROS are crucial for regulating several processes, such as development, memory, neuronal signaling, and vascular homeostasis. However, NOX-mediated excessive ROS generation is deeply involved in the damage of DNA, proteins, and lipids, leading to cell death in the pathogenesis of a wide range of diseases, namely neurodegenerative diseases. Future directions: It is essential to understand the role of NOX homologs in neurodegenerative disorders and the pathological mechanisms undergoing neurodegeneration mediated by increased levels of ROS. This further knowledge will allow the development of new specific NOX inhibitors and their application for neurodegenerative disease therapeutics. Antioxid. Redox Signal. 41, 522-541.}, } @article {pmid38760174, year = {2024}, author = {Pal, A and Grossmann, D and Glaß, H and Zimyanin, V and Günther, R and Catinozzi, M and Boeckers, TM and Sterneckert, J and Storkebaum, E and Petri, S and Wegner, F and Grill, SW and Pan-Montojo, F and Hermann, A}, title = {Glycolic acid and D-lactate-putative products of DJ-1-restore neurodegeneration in FUS - and SOD1-ALS.}, journal = {Life science alliance}, volume = {7}, number = {8}, pages = {}, pmid = {38760174}, issn = {2575-1077}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism/genetics ; *RNA-Binding Protein FUS/metabolism/genetics ; *Glycolates/metabolism/pharmacology ; *Mitochondria/metabolism ; *Protein Deglycase DJ-1/metabolism/genetics ; *Lactic Acid/metabolism ; *Superoxide Dismutase-1/metabolism/genetics ; Membrane Potential, Mitochondrial ; Motor Neurons/metabolism ; Lysosomes/metabolism ; }, abstract = {Amyotrophic lateral sclerosis (ALS) leads to death within 2-5 yr. Currently, available drugs only slightly prolong survival. We present novel insights into the pathophysiology of Superoxide Dismutase 1 (SOD1)- and in particular Fused In Sarcoma (FUS)-ALS by revealing a supposedly central role of glycolic acid (GA) and D-lactic acid (DL)-both putative products of the Parkinson's disease associated glyoxylase DJ-1. Combined, not single, treatment with GA/DL restored axonal organelle phenotypes of mitochondria and lysosomes in FUS- and SOD1-ALS patient-derived motoneurons (MNs). This was not only accompanied by restoration of mitochondrial membrane potential but even dependent on it. Despite presenting an axonal transport deficiency as well, TDP43 patient-derived MNs did not share mitochondrial depolarization and did not respond to GA/DL treatment. GA and DL also restored cytoplasmic mislocalization of FUS and FUS recruitment to DNA damage sites, recently reported being upstream of the mitochondrial phenotypes in FUS-ALS. Whereas these data point towards the necessity of individualized (gene-) specific therapy stratification, it also suggests common therapeutic targets across different neurodegenerative diseases characterized by mitochondrial depolarization.}, } @article {pmid38759931, year = {2024}, author = {Guo, X and Zhang, Z and Gu, J and Ke, P and Liu, J and Meng, Y and Zheng, W and Que, W and Fan, R and Luo, J and Xiao, F}, title = {FUDNC1-dependent mitophagy ameliorate motor neuron death in an amyotrophic lateral sclerosis mouse model.}, journal = {Neurobiology of disease}, volume = {197}, number = {}, pages = {106534}, doi = {10.1016/j.nbd.2024.106534}, pmid = {38759931}, issn = {1095-953X}, mesh = {Animals ; *Amyotrophic Lateral Sclerosis/metabolism/pathology/genetics ; *Mitophagy/physiology ; *Motor Neurons/metabolism/pathology ; *Mice, Transgenic ; Mice ; *Disease Models, Animal ; *Mitochondrial Proteins/metabolism/genetics ; Membrane Proteins/metabolism/genetics ; Humans ; Spinal Cord/metabolism/pathology ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is one of the most common neurodegenerative diseases, yet effective treatment is lacking. Moreover, the underlying pathomechanisms of ALS remain unclear, with impaired mitophagy function being increasingly recognized as a contributing factor. FUN14 domain-containing protein 1 (FUNDC1) is an autophagy receptor localized to the outer mitochondrial membrane and a mitochondrial membrane protein that mediates mitophagy and therefore considered as important factor in neurodegenerative diseases. However, its specific role in ALS is not yet clear. Therefore, this study aimed to investigate the regulatory role of FUNDC1 in ALS and determine its regulatory mechanisms. ALS transgenic mice were obtained and maintained under standard conditions. Cell lines were generated by stable transfection with hSOD1[G93A] or control vectors. Mice received intrathecal injections of AAV9 vectors expressing FUNDC1 or EGFP. Motor function was assessed through behavioral tests, and histological and immunostaining analyses were performed. Colocalization analysis was conducted in transfected cells, and protein expression was evaluated via western blotting. We first observed that FUNDC1 was significantly downregulated in the spinal cord tissues of SOD1[G93A] mice. FUNDC1 overexpression considerably improved locomotor activity and prolonged survival time in SOD1[G93A] mice. Mechanistically, reduced expression of FUNDC1 resulted in decreased mitophagy, as indicated by decreased recruitment through LC3 in SOD1[G93A] mice and cellular models. Consequently, this led to increased mitochondrial accumulation and cell apoptosis, exacerbating the ALS phenotype. Furthermore, we identified transcription factor FOXD3 as an essential upstream factor of FUNDC1, resulting in reduced transcription of FUNDC1 in ALS lesions. This study suggests a novel strategy of targeting FUNDC1-mediated mitophagy for developing therapeutic interventions to mitigate disease progression and improve outcomes for ALS patients.}, } @article {pmid38759788, year = {2024}, author = {Kumar, RP and Sivan, V and Bachir, H and Sarwar, SA and Ruzicka, F and O'Malley, GR and Lobo, P and Morales, IC and Cassimatis, ND and Hundal, JS and Patel, NV}, title = {Can Artificial Intelligence Mitigate Missed Diagnoses by Generating Differential Diagnoses for Neurosurgeons?.}, journal = {World neurosurgery}, volume = {187}, number = {}, pages = {e1083-e1088}, doi = {10.1016/j.wneu.2024.05.052}, pmid = {38759788}, issn = {1878-8769}, mesh = {Humans ; Diagnosis, Differential ; *Artificial Intelligence ; *Neurosurgeons ; *Missed Diagnosis ; Neurosurgery ; Diagnostic Errors ; }, abstract = {BACKGROUND/OBJECTIVE: Neurosurgery emphasizes the criticality of accurate differential diagnoses, with diagnostic delays posing significant health and economic challenges. As large language models (LLMs) emerge as transformative tools in healthcare, this study seeks to elucidate their role in assisting neurosurgeons with the differential diagnosis process, especially during preliminary consultations.

METHODS: This study employed 3 chat-based LLMs, ChatGPT (versions 3.5 and 4.0), Perplexity AI, and Bard AI, to evaluate their diagnostic accuracy. Each LLM was prompted using clinical vignettes, and their responses were recorded to generate differential diagnoses for 20 common and uncommon neurosurgical disorders. Disease-specific prompts were crafted using Dynamed, a clinical reference tool. The accuracy of the LLMs was determined based on their ability to identify the target disease within their top differential diagnoses correctly.

RESULTS: For the initial differential, ChatGPT 3.5 achieved an accuracy of 52.63%, while ChatGPT 4.0 performed slightly better at 53.68%. Perplexity AI and Bard AI demonstrated 40.00% and 29.47% accuracy, respectively. As the number of considered differentials increased from 2 to 5, ChatGPT 3.5 reached its peak accuracy of 77.89% for the top 5 differentials. Bard AI and Perplexity AI had varied performances, with Bard AI improving in the top 5 differentials at 62.11%. On a disease-specific note, the LLMs excelled in diagnosing conditions like epilepsy and cervical spine stenosis but faced challenges with more complex diseases such as Moyamoya disease and amyotrophic lateral sclerosis.

CONCLUSIONS: LLMs showcase the potential to enhance diagnostic accuracy and decrease the incidence of missed diagnoses in neurosurgery.}, } @article {pmid38759454, year = {2024}, author = {Wei, Y and Zhong, S and Yang, H and Wang, X and Lv, B and Bian, Y and Pei, Y and Xu, C and Zhao, Q and Wu, Y and Luo, D and Wang, F and Sun, H and Chen, Y}, title = {Current therapy in amyotrophic lateral sclerosis (ALS): A review on past and future therapeutic strategies.}, journal = {European journal of medicinal chemistry}, volume = {272}, number = {}, pages = {116496}, doi = {10.1016/j.ejmech.2024.116496}, pmid = {38759454}, issn = {1768-3254}, mesh = {*Amyotrophic Lateral Sclerosis/drug therapy ; Humans ; *Neuroprotective Agents/pharmacology/chemistry/therapeutic use ; Animals ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that affects the first and second motoneurons (MNs), associated with muscle weakness, paralysis and finally death. The exact etiology of the disease still remains unclear. Currently, efforts to develop novel ALS treatments which target specific pathomechanisms are being studied. The mechanisms of ALS pathogenesis involve multiple factors, such as protein aggregation, glutamate excitotoxicity, oxidative stress, mitochondrial dysfunction, apoptosis, inflammation etc. Unfortunately, to date, there are only two FDA-approved drugs for ALS, riluzole and edavarone, without curative treatment for ALS. Herein, we give an overview of the many pathways and review the recent discovery and preclinical characterization of neuroprotective compounds. Meanwhile, drug combination and other therapeutic approaches are also reviewed. In the last part, we analyze the reasons of clinical failure and propose perspective on the treatment of ALS in the future.}, } @article {pmid38759021, year = {2024}, author = {Pupillo, E and Al-Chalabi, A and Sassi, S and Arippol, E and Tinti, L and Vitelli, E and Copetti, M and Leone, MA and Bianchi, E}, title = {Methodological Quality of Clinical Trials in Amyotrophic Lateral Sclerosis: A Systematic Review.}, journal = {Journal of neuromuscular diseases}, volume = {11}, number = {4}, pages = {749-765}, pmid = {38759021}, issn = {2214-3602}, mesh = {*Amyotrophic Lateral Sclerosis/therapy ; Humans ; *Clinical Trials as Topic/standards ; *Research Design ; }, abstract = {BACKGROUND: More than 200 clinical trials have been performed worldwide in ALS so far, but no agents with substantial efficacy on disease progression have been found.

OBJECTIVE: To describe the methodological quality of all clinical trials performed in ALS and published before December 31, 2022.

METHODS: We conducted a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta Analyses.

RESULTS: 213 trials were included. 47.4% manuscripts described preclinical study evaluation, with a positive effect in all. 67.6% of trials were conducted with a parallel-arm design, while 12.7% were cross-over studies; 77% were randomized, while in 5.6% historical-controls were used for comparison. 70% of trials were double blind. Participant inclusion allowed forced vital capacity (or corresponding slow vital capacity)<50% in 15% cases, between 55-65% in 21.6%, between 70-80% in 14.1% reports, and 49.3% of the evaluated manuscripts did not provide a minimum value for respiratory capacity at inclusion. Disease duration was < 6-months in 6 studies, 7-36 months in 68, 37-60 months in 24, 8 trials requested more than 1-month of disease duration, while in 107 reports a disease duration was not described. Dropout rate was ≥20% in 30.5% trials, while it was not reported for 8.5%.

CONCLUSION: The methodological quality of the included studies was highly variable. Major issues to be addressed in future ALS clinical trials include: the requirement for standard animal toxicology and phase I studies, the resource-intensive nature of phase II-III studies, adequate study methodology and design, a good results reporting.}, } @article {pmid38758376, year = {2024}, author = {Li, X and Song, C and Wang, Y and Wang, J and Tang, Q and Wu, Z and Zhou, Y and Sun, J and Jia, Y and Lin, Z and Li, S}, title = {Accuracy of 14 intraocular lens power calculation formulas in extremely long eyes.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {262}, number = {11}, pages = {3619-3628}, pmid = {38758376}, issn = {1435-702X}, support = {2020SKC2002//Project Supported by Science and Technology Innovation Program of Socialization Investment of Hunan Province/ ; }, mesh = {Humans ; Retrospective Studies ; *Lenses, Intraocular ; *Refraction, Ocular/physiology ; *Axial Length, Eye ; Female ; Male ; Aged ; *Biometry/methods ; *Optics and Photonics ; Middle Aged ; Reproducibility of Results ; Visual Acuity ; Aged, 80 and over ; Adult ; Lens Implantation, Intraocular ; }, abstract = {PURPOSE: To compare the accuracy of 14 formulas in calculating intraocular lens (IOL) power in extremely long eyes with axial length (AL) over 30.0 mm.

METHODS: In this retrospective study, 211 eyes (211 patients) with ALs > 30.0 mm were successfully treated with cataract surgery without complications. Ocular biometric parameters were obtained from IOLMaster 700. Fourteen formulas were evaluated using the optimized A constants: Barrett Universal II (BUII), Kane, Emmetropia Verifying Optical (EVO) 2.0, PEARL-DGS, T2, SRK/T, Holladay 1, Holladay 2, Haigis and Wang-Koch AL adjusted formulas (SRK/Tmodified-W/K, Holladay 1modified-W/K, Holladay 1NP-modified-W/K, Holladay 2modified-W/K, Holladay 2NP-modified-W/K). The mean prediction error (PE) and standard deviation (SD), mean absolute errors (MAE), median absolute errors (MedAE), and the percentage of prediction errors (PEs) within ± 0.25 D, ± 0.50 D, ± 1.00 D were analyzed.

RESULTS: The Kane formula had the smallest MAE (0.43 D) and MedAE (0.34 D). The highest percentage of PE within ± 0.25 D was for EVO 2.0 (37.91%) and the Holladay 1NP-modified-W/K formulas (37.91%). The Kane formula had the highest percentage of PEs in the range of ± 0.50, ± 0.75, ± 1.00, and ± 2.00 D. There was no significant difference in PEs within ± 0.25, ± 0.50 ± 0.75 and ± 1.00 D between BUII, Kane, EVO 2.0 and Wang-Koch AL adjusted formulas (P > .05) by using Cochran's Q test. The Holladay 2modified-W/K formula has the lowest percentage of hyperopic outcomes (29.38%).

CONCLUSIONS: The BUII, Kane, EVO 2.0 and Wang-Koch AL adjusted formulas have comparable accuracy for IOL power calculation in eyes with ALs > 30.0 mm.}, } @article {pmid38758353, year = {2024}, author = {Mavroudis, I and Alexiou, P and Petridis, F and Ciobica, A and Balmus, IM and Gireadă, B and Gurzu, IL and Novac, O and Novac, B}, title = {Patients' and caregivers' attitudes towards patient assisted suicide or euthanasia in amyotrophic lateral sclerosis-a meta-analysis.}, journal = {Acta neurologica Belgica}, volume = {124}, number = {5}, pages = {1489-1498}, pmid = {38758353}, issn = {2240-2993}, mesh = {*Amyotrophic Lateral Sclerosis/psychology ; Humans ; *Suicide, Assisted/psychology ; *Caregivers/psychology ; *Euthanasia/psychology ; Attitude to Death ; }, abstract = {Assisted suicide and euthanasia are long debated topics in amyotrophic lateral sclerosis (ALS) patients care. We conducted a meta-analysis to evaluate the attitudes of ALS patients and their caregivers toward physician-assisted suicide (PAS) and euthanasia. Also, we were interested to identify the factors associated with the positive or negative attitude of patients and caregivers towards PAS/euthanasia. A thorough search of the online databases (PubMed, Cochrane Library, and Web of Science) was conducted and eligibility criteria according to the PRISMA guidelines were used to include the studies in the current meta-analysis. The assessment of the quality of the selected studies was carried out using a pre-specified set of criteria by Cochrane. The studies that were selected for this meta-analysis suggested that the expression of the wish to die is more likely correlated with depression, anxiety, hopelessness, and lack of optimism. The overall prevalence of considering PAS/euthanasia significantly varies in a dependent manner over the cultural, legal, and societal factors. In this context, we found that the opinion on this topic can be deeply personal and may vary widely among individuals and communities. Lower quality of life and lower religiosity were associated with a positive attitude toward PAS/euthanasia. On the other hand, patients who are more religious are less likely to choose PAS/euthanasia. Gender does not appear to play a significant role in determining attitudes towards PAS/euthanasia in ALS patients. Other factors, such as education and psychological state, could also be important. In conclusion, end-of-life decisions in ALS patients are complex and require careful consideration of individual values, beliefs, and preferences. Understanding the factors that influence a patient's attitude towards PAS/euthanasia can help healthcare providers to offer appropriate care and support for these patients and their families.}, } @article {pmid38758288, year = {2024}, author = {Qi, C and Kobayashi, R and Kawakatsu, S and Kametani, F and Scheres, SHW and Goedert, M and Hasegawa, M}, title = {Tau filaments with the chronic traumatic encephalopathy fold in a case of vacuolar tauopathy with VCP mutation D395G.}, journal = {Acta neuropathologica}, volume = {147}, number = {1}, pages = {86}, pmid = {38758288}, issn = {1432-0533}, support = {JSPS KAKENHI//Japanese society for the promotion of science/ ; JPMH20GB1002//Ministry of Health, Labour and Welfare/ ; JPMH23GB1003//Ministry of Health, Labour and Welfare/ ; MC_UP_A025-1013/MRC_/Medical Research Council/United Kingdom ; JP20K07922//Japanese society for the promotion of science/ ; MC_UP_A025_1013/MRC_/Medical Research Council/United Kingdom ; MC_U105184291/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Humans ; *Tauopathies/genetics/pathology ; *Chronic Traumatic Encephalopathy/pathology/genetics ; *tau Proteins/genetics/metabolism ; *Valosin Containing Protein/genetics ; *Mutation ; Vacuoles/pathology/ultrastructure ; Male ; Adenosine Triphosphatases/genetics ; Cell Cycle Proteins/genetics ; Middle Aged ; Frontotemporal Dementia/genetics/pathology ; Brain/pathology ; Female ; }, abstract = {Dominantly inherited mutation D395G in the gene encoding valosin-containing protein causes vacuolar tauopathy, a type of behavioural-variant frontotemporal dementia, with marked vacuolation and abundant filamentous tau inclusions made of all six brain isoforms. Here we report that tau inclusions were concentrated in layers II/III of the frontotemporal cortex in a case of vacuolar tauopathy. By electron cryomicroscopy, tau filaments had the chronic traumatic encephalopathy (CTE) fold. Tau inclusions of vacuolar tauopathy share this cortical location and the tau fold with CTE, subacute sclerosing panencephalitis and amyotrophic lateral sclerosis/parkinsonism-dementia complex, which are believed to be environmentally induced. Vacuolar tauopathy is the first inherited disease with the CTE tau fold.}, } @article {pmid38758193, year = {2024}, author = {Oliveira Santos, M and de Carvalho, M}, title = {Profiling tofersen as a treatment of superoxide dismutase 1 amyotrophic lateral sclerosis.}, journal = {Expert review of neurotherapeutics}, volume = {24}, number = {6}, pages = {549-553}, doi = {10.1080/14737175.2024.2355983}, pmid = {38758193}, issn = {1744-8360}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy/genetics ; *Superoxide Dismutase-1/genetics/metabolism ; Oligonucleotides/therapeutic use ; Oligonucleotides, Antisense/therapeutic use ; Biomarkers/blood ; }, abstract = {INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a rapidly progressive motor neuron disorder with a fatal outcome 3-5 years after disease onset due to respiratory complications. Superoxide dismutase 1 (SOD1) mutations are found in about 2% of all patients. Tofersen is a novel oligonucleotide antisense drug specifically developed to treat SOD1-ALS patients.

AREAS COVERED: Our review covers and discusses tofersen pharmacological properties and its phase I/II and III clinical trials results. Other available drugs and their limitations are also addressed.

EXPERT OPINION: VALOR study failed to meet the primary endpoint (change in the revised Amyotrophic Lateral Sclerosis Functional Rating Scale score from baseline to week 28, tofersen arm vs. placebo), but a significant reduction in plasma neurofilament light chain (NfL) levels was observed in tofersen arm (60% vs. 20%). PrefALS study has proposed plasma NfL has a potential biomarker for presymptomatic treatment, since it increases 6-12 months before phenoconversion. There is probably a delay between plasma NfL reduction and the clinical benefit. ATLAS study will allow more insights regarding tofersen clinical efficacy in disease progression rate, survival, and even disease onset delay in presymptomatic SOD1 carriers.}, } @article {pmid38758158, year = {2025}, author = {Zou, X and Shi, Y and Zhang, T and Huang, A and Cui, H and Wang, T}, title = {Electroacupuncture Combined with Chinese Herbal Medicine, Qidong Huoluo Granule, for Amyotrophic Lateral Sclerosis: An 8-Month Case Report.}, journal = {Alternative therapies in health and medicine}, volume = {31}, number = {4}, pages = {268-272}, pmid = {38758158}, issn = {1078-6791}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy/drug therapy ; Male ; Middle Aged ; *Electroacupuncture/methods ; *Drugs, Chinese Herbal/therapeutic use ; Combined Modality Therapy ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is an adult neurodegenerative disorder characterized by progressive muscle weakness and eventual paralysis, for which there is currently no curative treatment. Mainstream medical interventions primarily focus on providing supportive care. However, acupuncture offers promising avenues for alleviating symptoms and enhancing quality of life. Specific acupuncture points are targeted to address bulbar paralysis as well as paralysis affecting the upper and lower extremities.

OBJECTIVE: To investigate the efficacy of electroacupuncture combined with Chinese herbal medicine in delaying disease progression and alleviating symptoms of bulbar paralysis in patients with ALS.

CASE PRESENTATION: A 51-year-old male presented with a 4-year and 8-month history of weakness in his left arm and both legs, accompanied by muscle cramps and diminished coordination, which had rapidly worsened over the past year. ALS was diagnosed, and the patient was initiated on oral Riluzole (50 mg) and Qidong Huoluo granule, a Chinese herbal compound, administered twice daily. Concurrently, he underwent acupuncture treatment sessions twice weekly for over 8 months.

RESULTS: Following acupuncture therapy, the patient experienced gradual stabilization of symptoms, notably improvement in swallowing function. The combination of electroacupuncture and Qidong Huoluo granule resulted in sustained clinical enhancements post-treatment, including improvements in speech, coughing, articulation, and breathing.

CONCLUSION: Electroacupuncture therapy demonstrates the potential to slow disease progression and ameliorate symptoms of bulbar paralysis in ALS patients. However, further robust clinical research is imperative to explain the precise therapeutic role of electroacupuncture in managing this debilitating condition. Continued investigation into the efficacy and safety profile of electroacupuncture holds promise for advancing treatment modalities for ALS.}, } @article {pmid38757649, year = {2024}, author = {Lee, I and Mitsumoto, H and Lee, S and Kasarskis, E and Rosenbaum, M and Factor-Litvak, P and Nieves, JW}, title = {Reply to Glycemic Index/Load Effect on ALS Progression: Potential Interaction with Riluzole.}, journal = {Annals of neurology}, volume = {96}, number = {1}, pages = {208-209}, doi = {10.1002/ana.26971}, pmid = {38757649}, issn = {1531-8249}, support = {K23NS131586/NS/NINDS NIH HHS/United States ; K23NS131586/NS/NINDS NIH HHS/United States ; }, mesh = {*Amyotrophic Lateral Sclerosis/drug therapy ; Humans ; *Riluzole/therapeutic use/pharmacology ; *Disease Progression ; *Glycemic Index/drug effects ; Neuroprotective Agents/therapeutic use/pharmacology ; Blood Glucose/drug effects/metabolism ; }, } @article {pmid38756356, year = {2024}, author = {Rennie, O and Sharma, M and Helwa, N}, title = {Colorectal anastomotic leakage: a narrative review of definitions, grading systems, and consequences of leaks.}, journal = {Frontiers in surgery}, volume = {11}, number = {}, pages = {1371567}, pmid = {38756356}, issn = {2296-875X}, abstract = {BACKGROUND: Anastomotic leaks (ALs) are a significant and feared postoperative complication, with incidence of up to 30% despite advances in surgical techniques. With implications such as additional interventions, prolonged hospital stays, and hospital readmission, ALs have important impacts at the level of individual patients and healthcare providers, as well as healthcare systems as a whole. Challenges in developing unified definitions and grading systems for leaks have proved problematic, despite acknowledgement that colorectal AL is a critical issue in intestinal surgery with serious consequences. The aim of this study was to construct a narrative review of literature surrounding definitions and grading systems for ALs, and consequences of this postoperative complication.

METHODS: A literature review was conducted by examining databases including PubMed, Web of Science, OVID Embase, Google Scholar, and Cochrane library databases. Searches were performed with the following keywords: anastomosis, anastomotic leak, colorectal, surgery, grading system, complications, risk factors, and consequences. Publications that were retrieved underwent further assessment to ensure other relevant publications were identified and included.

RESULTS: A universally accepted definition and grading system for ALs continues to be lacking, leading to variability in reported incidence in the literature. Additional factors add to variability in estimates, including differences in the anastomotic site and institutional/individual differences in operative technique. Various groups have worked to publish guidelines for defining and grading AL, with the International Study Group of Rectal Cancer (ISGRC/ISREC) definition the current most recommended universal definition for colorectal AL. The burden of AL on patients, healthcare providers, and hospitals is well documented in evidence from leak consequences, such as increased morbidity and mortality, higher reoperation rates, and increased readmission rates, among others.

CONCLUSIONS: Colorectal AL remains a significant challenge in intestinal surgery, despite medical advancements. Understanding the progress made in defining and grading leaks, as well as the range of negative outcomes that arise from AL, is crucial in improving patient care, reduce surgical mortality, and drive further advancements in earlier detection and treatment of AL.}, } @article {pmid38755145, year = {2024}, author = {Garcia-Montojo, M and Fathi, S and Rastegar, C and Simula, ER and Doucet-O'Hare, T and Cheng, YHH and Abrams, RPM and Pasternack, N and Malik, N and Bachani, M and Disanza, B and Maric, D and Lee, MH and Wang, H and Santamaria, U and Li, W and Sampson, K and Lorenzo, JR and Sanchez, IE and Mezghrani, A and Li, Y and Sechi, LA and Pineda, S and Heiman, M and Kellis, M and Steiner, J and Nath, A}, title = {TDP-43 proteinopathy in ALS is triggered by loss of ASRGL1 and associated with HML-2 expression.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {4163}, pmid = {38755145}, issn = {2041-1723}, support = {I01 BX002466/BX/BLRD VA/United States ; NS003130//U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; }, mesh = {Animals ; Female ; Humans ; Male ; Mice ; *Amyotrophic Lateral Sclerosis/metabolism/genetics/pathology ; *Asparaginase/genetics/metabolism ; Autoantigens/genetics/metabolism ; Brain/metabolism/pathology ; *DNA-Binding Proteins/metabolism/genetics ; Motor Cortex/metabolism/pathology ; *Neurons/metabolism/pathology ; *TDP-43 Proteinopathies/metabolism/pathology/genetics ; Endogenous Retroviruses/genetics/metabolism ; }, abstract = {TAR DNA-binding protein 43 (TDP-43) proteinopathy in brain cells is the hallmark of amyotrophic lateral sclerosis (ALS) but its cause remains elusive. Asparaginase-like-1 protein (ASRGL1) cleaves isoaspartates, which alter protein folding and susceptibility to proteolysis. ASRGL1 gene harbors a copy of the human endogenous retrovirus HML-2, whose overexpression contributes to ALS pathogenesis. Here we show that ASRGL1 expression was diminished in ALS brain samples by RNA sequencing, immunohistochemistry, and western blotting. TDP-43 and ASRGL1 colocalized in neurons but, in the absence of ASRGL1, TDP-43 aggregated in the cytoplasm. TDP-43 was found to be prone to isoaspartate formation and a substrate for ASRGL1. ASRGL1 silencing triggered accumulation of misfolded, fragmented, phosphorylated and mislocalized TDP-43 in cultured neurons and motor cortex of female mice. Overexpression of ASRGL1 restored neuronal viability. Overexpression of HML-2 led to ASRGL1 silencing. Loss of ASRGL1 leading to TDP-43 aggregation may be a critical mechanism in ALS pathophysiology.}, } @article {pmid38753998, year = {2025}, author = {Yin, Z and Yang, Z and Liu, Y and Zhao, L and Liang, F}, title = {Oxidative stress and neurodegenerative diseases: a bidirectional Mendelian randomization study.}, journal = {Nutritional neuroscience}, volume = {28}, number = {1}, pages = {107-115}, doi = {10.1080/1028415X.2024.2352195}, pmid = {38753998}, issn = {1476-8305}, mesh = {*Mendelian Randomization Analysis ; Humans ; *Oxidative Stress ; *Neurodegenerative Diseases/genetics ; *Genome-Wide Association Study ; Alzheimer Disease/genetics ; Uric Acid/blood ; Zinc/blood ; Amyotrophic Lateral Sclerosis/genetics ; Parkinson Disease/genetics ; alpha-Tocopherol/blood ; Biomarkers/blood ; }, abstract = {INTRODUCTION: Oxidative stress (OS) has been linked to neurodegenerative diseases in numerous epidemiological studies; however, whether it is a pathogenesis or a downstream factor remains controversial.

METHODS: A two-sample bidirectional Mendelian randomization (MR) analysis was implemented to examine evidence of causality of 15 OS injury markers with 3 major neurodegenerative diseases using available genome-wide association studies statistics. As a main approach, inverse-variance weighted (IVW) analysis was performed. The weighted-median (WM) analysis was used to validate the relationship. In order to investigate the existence of horizontal pleiotropy and correct the IVW estimate, the Radial MR approach was applied. To gauge the consistency and robustness of the findings, several sensitivity and pleiotropy analyses were used. For this analysis, p < 0.05 indicates a nominally causal association; according to the Bonferroni correction test, p < 0.0011 indicates a statistically significant causal association.

RESULTS: Via IVW and WM, in directional MR, it was genetically predicted that zinc was nominally causally correlated with the risk of Parkinson's disease but not after Bonferroni correction test; alpha-tocopherol was nominally causally correlated with the risk of Amyotrophic lateral sclerosis (ALS) but not after Bonferroni correction test; furthermore, in reverse MR, it was genetically predicted that Alzheimer's disease was causally correlated with uric acid but not after Bonferroni correction test. These above findings were stable across sensitivity and pleiotropy analyses.

CONCLUSIONS: Based on the current study, there is no authentic genetic causal association between OS biomarkers and neurodegenerative diseases. The complex relationship is required to be confirmed in future experimental research.}, } @article {pmid38753768, year = {2024}, author = {Prasad, K and Hassan, MI and Raghuvanshi, S and Kumar, V}, title = {Understanding the relationship between cerebellum and the frontal-cortex region of C9orf72-related amyotrophic lateral sclerosis: A comparative analysis of genetic features.}, journal = {PloS one}, volume = {19}, number = {5}, pages = {e0301267}, pmid = {38753768}, issn = {1932-6203}, mesh = {Aged ; Female ; Humans ; Male ; Middle Aged ; *Amyotrophic Lateral Sclerosis/genetics/pathology/metabolism ; C9orf72 Protein/genetics/metabolism ; *Cerebellum/metabolism/pathology ; *Frontal Lobe/metabolism/pathology ; Frontotemporal Dementia/genetics/pathology/metabolism ; MicroRNAs/genetics/metabolism ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a relentlessly progressive and fatal neurodegenerative diseases for which at present no cure is available. Despite the extensive research the progress from diagnosis to prognosis in ALS and frontotemporal dementia (FTD) has been slow which represents suboptimal understanding of disease pathophysiological processes. In recent studies, several genes have been associated with the ALS and FTD diseases such as SOD1, TDP43, and TBK1, whereas the hexanucleotide GGGGCC repeat expansion (HRE) in C9orf72 gene is a most frequent cause of ALS and FTD, that has changed the understanding of these diseases.

METHODS: The goal of this study was to identify and spatially determine differential gene expression signature differences between cerebellum and frontal cortex in C9orf72-associated ALS (C9-ALS), to study the network properties of these differentially expressed genes, and to identify miRNAs targeting the common differentially expressed genes in both the tissues. This study thus highlights underlying differential cell susceptibilities to the disease mechanisms in C9-ALS and suggesting therapeutic target selection in C9-ALS.

RESULTS: In this manuscript, we have identified that the genes involved in neuron development, protein localization and transcription are mostly enriched in cerebellum of C9-ALS patients, while the UPR-related genes are enriched in the frontal cortex. Of note, UPR pathway genes were mostly dysregulated both in the C9-ALS cerebellum and frontal cortex. Overall, the data presented here show that defects in normal RNA processing and the UPR pathway are the pathological hallmarks of C9-ALS. Interestingly, the cerebellum showed more strong transcriptome changes than the frontal cortex.

CONCLUSION: Interestingly, the cerebellum region showed more significant transcriptomic changes as compared to the frontal cortex region suggesting its active participation in the disease process. This nuanced understanding may offer valuable insights for the development of targeted therapeutic strategies aimed at mitigating disease progression in C9-ALS.}, } @article {pmid38751620, year = {2024}, author = {Shojaei, M and Zhou, Q and Palumbo, G and Schaefer, R and Kaskinoro, J and Vehmaan-Kreula, P and Bartenstein, P and Brendel, M and Edbauer, D and Lindner, S}, title = {Development and Preclinical Evaluation of a Copper-64-Labeled Antibody Targeting Glycine-Alanine Dipeptides for PET Imaging of C9orf72-Associated Amyotrophic Lateral Sclerosis/Frontotemporal Dementia.}, journal = {ACS pharmacology & translational science}, volume = {7}, number = {5}, pages = {1404-1414}, pmid = {38751620}, issn = {2575-9108}, abstract = {Aggregating poly(glycine-alanine) (poly-GA) is derived from the unconventional translation of the pathogenic intronic hexanucleotide repeat expansion in the C9orf72 gene, which is the most common genetic cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). Poly-GA accumulates predominantly in neuronal cytoplasmic inclusions unique to C9orf72 ALS/FTD patients. Poly-GA is, therefore, a promising target for PET/CT imaging of FTD/ALS to monitor disease progression and therapeutic interventions. A novel [64]Cu-labeled anti-GA antibody (mAb1A12) targeting the poly-GA protein was developed and evaluated in a transgenic mouse model. It was obtained with high radiochemical purity (RCP), radiochemical yield (RCY), and specific activity, and showed high stability in vitro and ex vivo and specifically bound to poly-GA. The affinity of NODAGA-mAb1A12 for poly-GA was not affected by this modification. [[64]Cu]Cu-NODAGA-mAb1A12 was injected into transgenic mice expressing GFP-(GA)175 in excitatory neurons driven by Camk2a-Cre and in control littermates. PET/CT imaging was performed at 2, 20, and 40 h post-injection (p.i.) and revealed a higher accumulation in the cortex in transgenic mice than in wild-type mice, as reflected by higher standardized uptake value ratios (SUVR) using the cerebellum as the reference region. The organs were isolated for biodistribution and ex vivo autoradiography. Autoradiography revealed a higher cortex-to-cerebellum ratio in the transgenic mice than in the controls. Results from autoradiography were validated by immunohistochemistry and poly-GA immunoassays. Moreover, we confirmed antibody uptake in the CNS in a pharmacokinetic study of the perfused tissues. In summary, [[64]Cu]Cu-NODAGA-mAb1A12 demonstrated favorable in vitro characteristics and an increased relative binding in poly-GA transgenic mice compared to wild-type mice in vivo. Our results with this first-in-class radiotracer suggested that targeting poly-GA is a promising approach for PET/CT imaging in FTD/ALS.}, } @article {pmid38751168, year = {2024}, author = {Raffaele, S and Nguyen, N and Milanese, M and Mannella, FC and Boccazzi, M and Frumento, G and Bonanno, G and Abbracchio, MP and Bonifacino, T and Fumagalli, M}, title = {Montelukast improves disease outcome in SOD1[G93A] female mice by counteracting oligodendrocyte dysfunction and aberrant glial reactivity.}, journal = {British journal of pharmacology}, volume = {181}, number = {18}, pages = {3303-3326}, doi = {10.1111/bph.16408}, pmid = {38751168}, issn = {1476-5381}, support = {GPR17ALS-1//AriSLA ETS - Fondazione Italiana di ricerca per la SLA/ ; 2017NSXP8J//Italian Ministry of University and Research (MUR)/ ; PE0000006//#NEXTGENERATIONEU (NGEU) and the Italian Ministry of University and Research (MUR), NRRP - National Recovery and Resilience Plan/ ; //Foundation Bellandi Bernardoni/ ; }, mesh = {Animals ; Female ; *Cyclopropanes/pharmacology ; *Quinolines/pharmacology ; *Acetates/pharmacology/therapeutic use ; *Oligodendroglia/drug effects/metabolism/pathology ; *Sulfides/pharmacology ; *Amyotrophic Lateral Sclerosis/drug therapy/genetics/pathology ; *Mice, Transgenic ; Mice ; Male ; Receptors, Leukotriene/metabolism/genetics ; Receptors, G-Protein-Coupled/metabolism/genetics ; Superoxide Dismutase-1/genetics/metabolism ; Mice, Inbred C57BL ; Disease Models, Animal ; Spinal Cord/drug effects/metabolism/pathology ; Microglia/drug effects/metabolism/pathology ; Nerve Tissue Proteins ; }, abstract = {BACKGROUND AND PURPOSE: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by progressive motor neuron (MN) loss and consequent muscle atrophy, for which no effective therapies are available. Recent findings reveal that disease progression is fuelled by early aberrant neuroinflammation and the loss of oligodendrocytes with neuroprotective and remyelinating properties. On this basis, pharmacological interventions capable of restoring a pro-regenerative local milieu and re-establish proper oligodendrocyte functions may be beneficial.

EXPERIMENTAL APPROACH: Here, we evaluated the in vivo therapeutic effects of montelukast (MTK), an antagonist of the oligodendroglial G protein-coupled receptor 17 (GPR17) and of cysteinyl-leukotriene receptor 1 (CysLT1R) receptors on microglia and astrocytes, in the SOD1[G93A] ALS mouse model. We chronically treated SOD1[G93A] mice with MTK, starting from the early symptomatic disease stage. Disease progression was assessed by behavioural and immunohistochemical approaches.

KEY RESULTS: Oral MTK treatment significantly extended survival probability, delayed body weight loss and ameliorated motor functionalityonly in female SOD1[G93A] mice. Noteworthy, MTK significantly restored oligodendrocyte maturation and induced significant changes in the reactive phenotype and morphological features of microglia/macrophages and astrocytes in the spinal cord of female SOD1[G93A] mice, suggesting enhanced pro-regenerative functions. Importantly, concomitant MN preservation has been detected after MTK administration. No beneficial effects were observed in male mice, highlighting a sex-based difference in the protective activity of MTK.

CONCLUSIONS AND IMPLICATIONS: Our results provide the first preclinical evidence indicating that repurposing of MTK, a safe and marketed anti-asthmatic drug, may be a promising sex-specific strategy for personalized ALS treatment.}, } @article {pmid38750212, year = {2024}, author = {Leventoux, N and Morimoto, S and Ishikawa, M and Nakamura, S and Ozawa, F and Kobayashi, R and Watanabe, H and Supakul, S and Okamoto, S and Zhou, Z and Kobayashi, H and Kato, C and Hirokawa, Y and Aiba, I and Takahashi, S and Shibata, S and Takao, M and Yoshida, M and Endo, F and Yamanaka, K and Kokubo, Y and Okano, H}, title = {Aberrant CHCHD2-associated mitochondriopathy in Kii ALS/PDC astrocytes.}, journal = {Acta neuropathologica}, volume = {147}, number = {1}, pages = {84}, pmid = {38750212}, issn = {1432-0533}, support = {JP15J03921//Japan Society for the Promotion of Science/ ; JP18K07368//Japan Society for the Promotion of Science/ ; JP18KK0239//Japan Society for the Promotion of Science/ ; JP19K17002//Japan Society for the Promotion of Science/ ; JP19K08002//Japan Society for the Promotion of Science/ ; JP21H05278//Japan Society for the Promotion of Science/ ; JP22K07500//Japan Society for the Promotion of Science/ ; JP22K15736//Japan Society for the Promotion of Science/ ; JP17K10083//Japan Society for the Promotion of Science/ ; JP20H03567//Japan Society for the Promotion of Science/ ; JP22K18388//Japan Society for the Promotion of Science/ ; JP23H02882//Japan Society for the Promotion of Science/ ; JP22K07500//Japan Society for the Promotion of Science/ ; JP21K06417//Japan Society for the Promotion of Science/ ; JP18K06506//Japan Society for the Promotion of Science/ ; JP22H04923//Japan Society for the Promotion of Science/ ; JP25305030//Japan Society for the Promotion of Science/ ; JP15K09364//Japan Society for the Promotion of Science/ ; JP17H01689//Japan Society for the Promotion of Science/ ; JP18K07514//Japan Society for the Promotion of Science/ ; JP18K07368//Japan Society for the Promotion of Science/ ; JP20H00485//Japan Society for the Promotion of Science/ ; JP21F21410//Japan Society for the Promotion of Science/ ; JP21H05273//Japan Society for the Promotion of Science/ ; JP22KF0333//Japan Society for the Promotion of Science/ ; JP23bm1123046//Japan Agency for Medical Research and Development/ ; JP23kk0305024//Japan Agency for Medical Research and Development/ ; JP22bm0804023//Japan Agency for Medical Research and Development/ ; JP22gm6510006//Japan Agency for Medical Research and Development/ ; JP21wm0425019//Japan Agency for Medical Research and Development/ ; JP17ek0109139//Japan Agency for Medical Research and Development/ ; JP22bm0804003//Japan Agency for Medical Research and Development/ ; JP20ek0109395//Japan Agency for Medical Research and Development/ ; JP20ek0109329//Japan Agency for Medical Research and Development/ ; JP21wm0425009//Japan Agency for Medical Research and Development/ ; JP23bm1423002//Japan Agency for Medical Research and Development/ ; H29-Nanchi-Ippan-085//Research Committee of CNS Degenerative Diseases, Research on Policy Planning and Evaluation for Rare and Intractable Diseases/ ; JP18KK0239//Japanese Foundation for Research and Promotion of Endoscopy/ ; JP16H06277//MEXT/ ; }, mesh = {Female ; Humans ; Male ; *Amyotrophic Lateral Sclerosis/pathology/genetics/metabolism ; *Astrocytes/pathology/metabolism ; *DNA-Binding Proteins/metabolism/genetics ; Mitochondria/pathology/metabolism ; *Mitochondrial Proteins/genetics/metabolism ; *Transcription Factors/genetics/metabolism ; }, abstract = {Amyotrophic Lateral Sclerosis/Parkinsonism-Dementia Complex (ALS/PDC), a rare and complex neurological disorder, is predominantly observed in the Western Pacific islands, including regions of Japan, Guam, and Papua. This enigmatic condition continues to capture medical attention due to affected patients displaying symptoms that parallel those seen in either classical amyotrophic lateral sclerosis (ALS) or Parkinson's disease (PD). Distinctly, postmortem examinations of the brains of affected individuals have shown the presence of α-synuclein aggregates and TDP-43, which are hallmarks of PD and classical ALS, respectively. These observations are further complicated by the detection of phosphorylated tau, accentuating the multifaceted proteinopathic nature of ALS/PDC. The etiological foundations of this disease remain undetermined, and genetic investigations have yet to provide conclusive answers. However, emerging evidence has implicated the contribution of astrocytes, pivotal cells for maintaining brain health, to neurodegenerative onset, and likely to play a significant role in the pathogenesis of ALS/PDC. Leveraging advanced induced pluripotent stem cell technology, our team cultivated multiple astrocyte lines to further investigate the Japanese variant of ALS/PDC (Kii ALS/PDC). CHCHD2 emerged as a significantly dysregulated gene when disease astrocytes were compared to healthy controls. Our analyses also revealed imbalances in the activation of specific pathways: those associated with astrocytic cilium dysfunction, known to be involved in neurodegeneration, and those related to major neurological disorders, including classical ALS and PD. Further in-depth examinations revealed abnormalities in the mitochondrial morphology and metabolic processes of the affected astrocytes. A particularly striking observation was the reduced expression of CHCHD2 in the spinal cord, motor cortex, and oculomotor nuclei of patients with Kii ALS/PDC. In summary, our findings suggest a potential reduction in the support Kii ALS/PDC astrocytes provide to neurons, emphasizing the need to explore the role of CHCHD2 in maintaining mitochondrial health and its implications for the disease.}, } @article {pmid38749729, year = {2025}, author = {Kunieda, K and Hayashi, Y and Fujishima, I and Shimohata, T}, title = {Weight and Muscle Mass Loss Associated with Acute Disease Can Be Reversed with Appropriate Nutrition Therapy and Exercise in a Patient with Amyotrophic Lateral Sclerosis.}, journal = {Internal medicine (Tokyo, Japan)}, volume = {64}, number = {1}, pages = {133-136}, pmid = {38749729}, issn = {1349-7235}, mesh = {Humans ; Male ; *Amyotrophic Lateral Sclerosis/complications/rehabilitation/therapy/diet therapy/physiopathology ; Aged, 80 and over ; *Exercise Therapy/methods ; *Weight Loss/physiology ; Nutrition Therapy/methods ; Acute Disease ; Deglutition Disorders/etiology/rehabilitation/therapy/physiopathology ; Muscle Strength/physiology ; Body Composition ; Treatment Outcome ; }, abstract = {Nutritional interventions targeting weight loss are useful for the treatment of amyotrophic lateral sclerosis (ALS). However, the changes in body composition after nutritional intervention remain unclear. We herein present a patient with ALS who experienced an increased weight and muscle mass owing to nutritional therapy and physical exercise. An 86-year-old man presented with dysphagia and dysarthria. The patient was diagnosed with bulbar-type ALS. As weight loss progressed, a gastrostomy was performed. After 21 months of disease onset, gastrointestinal bleeding due to a bumper ulcer led to further weight loss (from 40.2 kg to 36.8 kg). The patient experienced difficulty walking and ingesting food orally. Although the total daily energy expenditure (TDEE) was estimated to be 1,122 kcal/day, an intake of 1,500 kcal/day beyond the calculated TDEE was administered. The patient continued to perform daily voluntary exercises in addition to his usual rehabilitation. After 5 months, his weight increased from 36.8 kg to 40.4 kg. Muscle mass increased from 25.1 kg to 30.1 kg, as measured using a multifrequency bioelectrical impedance device. Muscle strength improved from 8.5/10.0 kg to 15.0/18.0 kg in grip strength and from 15.2 kPa to 20.4 kPa in tongue pressure. The patient's physical and swallowing functions also improved. In patients with ALS, a decreased body weight and muscle mass due to acute disease may be improved by appropriate nutritional therapy and physical exercise.}, } @article {pmid38749539, year = {2024}, author = {Schwartze, JT and Das, S and Suggitt, D and Baxter, J and Tunstall, S and Ronan, N and Stannard, H and Rezgui, A and Jafar, W and Baxter, DN}, title = {Ward-based in situ simulation: lessons learnt from a UK District General Hospital.}, journal = {BMJ open quality}, volume = {13}, number = {2}, pages = {}, pmid = {38749539}, issn = {2399-6641}, mesh = {Humans ; United Kingdom ; Male ; Female ; *Patient Care Team/standards/statistics & numerical data ; Hospitals, General/statistics & numerical data ; Clinical Competence/statistics & numerical data/standards ; Simulation Training/methods/statistics & numerical data/standards ; Hospitals, District/statistics & numerical data ; Adult ; Patient Safety/standards/statistics & numerical data ; }, abstract = {INTRODUCTION: In situ simulation (ISS) enables multiprofessional healthcare teams to train for real emergencies in their own working environment and identify latent patient safety threats. This study aimed to determine ISS impact on teamwork, technical skill performance, healthcare staff perception and latent error identification during simulated medical emergencies.

MATERIALS AND METHODS: Unannounced ISS sessions (n=14, n=75 staff members) using a high-fidelity mannequin were conducted in medical, paediatric and rehabilitation wards at Stepping Hill Hospital (Stockport National Health Service Foundation Trust, UK). Each session encompassed a 15 min simulation followed by a 15 min faculty-led debrief.

RESULTS: The clinical team score revealed low overall teamwork performances during simulated medical emergencies (mean±SEM: 4.3±0.5). Linear regression analysis revealed that overall communication (r=0.9, p<0.001), decision-making (r=0.77, p<0.001) and overall situational awareness (r=0.73, p=0.003) were the strongest statistically significant predictors of overall teamwork performance. Neither the number of attending healthcare professionals, their professional background, age, gender, degree of clinical experience, level of resuscitation training or previous simulation experience statistically significantly impacted on overall teamwork performance. ISS positively impacted on healthcare staff confidence and clinical training. Identified safety threats included unknown location of intraosseous kits, poor/absent airway management, incomplete A-E assessments, inability to activate the major haemorrhage protocol, unknown location/dose of epinephrine for anaphylaxis management, delayed administration of epinephrine and delayed/absence of attachment of pads to the defibrillator as well as absence of accessing ALS algorithms, poor chest compressions and passive behaviour during simulated cardiac arrests.

CONCLUSION: Poor demonstration of technical/non-technical skills mandate regular ISS interventions for healthcare professionals of all levels. ISS positively impacts on staff confidence and training and drives identification of latent errors enabling improvements in workplace systems and resources.}, } @article {pmid38748878, year = {2024}, author = {Koopman, M and Güngördü, L and Janssen, L and Seinstra, RI and Richmond, JE and Okerlund, N and Wardenaar, R and Islam, P and Hogewerf, W and Brown, AEX and Jorgensen, EM and Nollen, EAA}, title = {Rebalancing the motor circuit restores movement in a Caenorhabditis elegans model for TDP-43 toxicity.}, journal = {Cell reports}, volume = {43}, number = {5}, pages = {114204}, doi = {10.1016/j.celrep.2024.114204}, pmid = {38748878}, issn = {2211-1247}, support = {P40 OD010440/OD/NIH HHS/United States ; }, mesh = {Animals ; *Caenorhabditis elegans/metabolism ; Caenorhabditis elegans Proteins/metabolism/genetics ; Cholinergic Neurons/metabolism ; *Disease Models, Animal ; *DNA-Binding Proteins/metabolism/genetics ; GABAergic Neurons/metabolism ; Locomotion ; Motor Neurons/metabolism ; Movement ; Synaptic Transmission ; *TDP-43 Proteinopathies/genetics/metabolism ; }, abstract = {Amyotrophic lateral sclerosis can be caused by abnormal accumulation of TAR DNA-binding protein 43 (TDP-43) in the cytoplasm of neurons. Here, we use a C. elegans model for TDP-43-induced toxicity to identify the biological mechanisms that lead to disease-related phenotypes. By applying deep behavioral phenotyping and subsequent dissection of the neuromuscular circuit, we show that TDP-43 worms have profound defects in GABA neurons. Moreover, acetylcholine neurons appear functionally silenced. Enhancing functional output of repressed acetylcholine neurons at the level of, among others, G-protein-coupled receptors restores neurotransmission, but inefficiently rescues locomotion. Rebalancing the excitatory-to-inhibitory ratio in the neuromuscular system by simultaneous stimulation of the affected GABA- and acetylcholine neurons, however, not only synergizes the effects of boosting individual neurotransmitter systems, but instantaneously improves movement. Our results suggest that interventions accounting for the altered connectome may be more efficient in restoring motor function than those solely focusing on diseased neuron populations.}, } @article {pmid38748695, year = {2024}, author = {Kim, HS and Woo, H and Choi, SJ and Baek, JG and Ryu, JS and Shin, HI and Park, KS and Beom, J}, title = {Factors associated with adherence to noninvasive positive pressure ventilation in amyotrophic lateral sclerosis.}, journal = {PloS one}, volume = {19}, number = {5}, pages = {e0302515}, pmid = {38748695}, issn = {1932-6203}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy/physiopathology ; Female ; Male ; Middle Aged ; *Positive-Pressure Respiration/methods ; *Noninvasive Ventilation ; Aged ; Retrospective Studies ; Blood Gas Analysis ; Length of Stay ; Patient Compliance ; Respiratory Function Tests ; Adult ; }, abstract = {INTRODUCTION: This cohort study aimed to investigate the factors associated with noninvasive positive pressure ventilation adherence and assess the long-term effects of noninvasive positive pressure ventilation adherence in patients with amyotrophic lateral sclerosis (ALS).

METHODS: The medical records of patients with ALS admitted to a tertiary hospital for noninvasive positive pressure ventilation initiation were retrospectively reviewed. Pulmonary function parameters, variables of blood gas analysis, the site of symptom onset, the time from onset and diagnosis to noninvasive positive pressure ventilation application, ALS Functional Rating Scale-Revised, neurophysiological index, and the length of hospital stay were evaluated. The adherence to noninvasive positive pressure ventilation was defined as the use of noninvasive positive pressure ventilation for ≥ 2 h/day or ≥ 4 h/day. The correlations between noninvasive positive pressure ventilation adherence or length of hospital stay and other clinical parameters were analyzed.

RESULTS: Fifty-one patients with ALS were included in the study. The time from onset and diagnosis to NIPPV application was reduced by 16 months in the adherent group than that in the non-adherent group; however, the parameters of blood gas analysis and pulmonary function tests did not differ significantly between the groups. Furthermore, the neurophysiological index of the abductor digiti minimi muscle was higher by 4.05 in the adherent group than that in the non-adherent group. The adherence to noninvasive positive pressure ventilation prolonged tracheostomy-free survival compared to that of non-adherence. Desaturation events, lower forced vital capacity, last pCO2, bicarbonate, and base excess, and higher differences in pCO2, were associated with an increase in the length of hospital stay.

CONCLUSIONS: Noninvasive positive pressure ventilation application shortly after symptom onset and ALS diagnosis in patients with CO2 retention and reduced forced vital capacity can be considered for successful adherence. Adherence to noninvasive positive pressure ventilation may result in reduced tracheostomy conversion rates and prolonged tracheostomy-free survival.}, } @article {pmid38748065, year = {2024}, author = {Lu, T and Luo, L and Yang, J and Cheng, X and Sun, J}, title = {Circulating Levels of T-Cell Traits and the Risk of Amyotrophic Lateral Sclerosis: A Mendelian Randomization Study.}, journal = {Molecular neurobiology}, volume = {61}, number = {12}, pages = {10529-10537}, pmid = {38748065}, issn = {1559-1182}, support = {WZ21M01 and WX20C35//the Wuhan Municipal Health Commission/ ; 2019YFC1708601//the National Key Research and Development Program of China/ ; SZ2021ZZ14//the Specific Fund of State Key Laboratory of Dampness Syndrome of Chinese Medicine/ ; 2017B030314176, 2018-75, and 2019-140//the Guangdong Provincial Key Laboratory of Research on Emergency in traditional Chinese medicine (TCM)/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/genetics/blood ; Humans ; *Mendelian Randomization Analysis ; *Genome-Wide Association Study ; Risk Factors ; Genetic Predisposition to Disease ; T-Lymphocytes/immunology/metabolism ; Polymorphism, Single Nucleotide/genetics ; Receptors, CCR7/genetics/metabolism ; }, abstract = {Amyotrophic lateral sclerosis (ALS) represents a rare and potentially fatal neurodegenerative disease. Diverse T-cell subsets could potentially exert diametrically opposite impacts upon ALS development. A two-sample Mendelian randomization (MR) analysis was performed to investigate the correlation between 244 T-cell subsets and ALS risk. Genetic instrumental variables were procured from a standard genome-wide association study (GWAS) that encompassed 244 T-cell subsets in 3757 individuals of European lineage. ALS-related data were collected from a GWAS comprising 20,806 ALS instances and 59,804 European control participants. Multiple sensitivity analyses were performed to verify the robustness of the significant results. Reverse MR analysis was used for delineating the effects of ALS on the characteristics of T-cells. After multiple comparison corrections, 24 out of the 244 subtypes demonstrated a potential association with ALS risk. Significantly, 75% of these associations encompassed the expression of the CD3 on diverse T-cell subtypes, revealing a highly consistent inverse relation to ALS risk. The proportion of T regulatory cells (Tregs) in CD4+ T cells and secreting Tregs in CD4+ T cells demonstrated negative associations with the risk of ALS. CCR7 expression on naive CD4+ T cells and CCR7 expression on naive CD8+ T cells showed positive associations with ALS risk. Certain T-cell subsets, particularly those identified by CD3 expression on terminally differentiated CD8+ T cells, proportions of Tregs, and CCR7 expression, indicated an association with ALS risk. These findings harmonize with and extend previous observational studies investigating the involvement of T lymphocyte subset-induced immunological processes in ALS.}, } @article {pmid38747354, year = {2024}, author = {Borghero, G and Pierri, V and Pili, F and Muroni, A and Ercoli, T and Pateri, MI and Pilotto, S and Maccabeo, A and Chiò, A and Defazio, G}, title = {Percutaneous gastrostomy, mechanical ventilation and survival in amyotrophic lateral sclerosis: an observational study in an incident cohort.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {25}, number = {5-6}, pages = {563-569}, doi = {10.1080/21678421.2024.2351185}, pmid = {38747354}, issn = {2167-9223}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/mortality/therapy ; *Gastrostomy/methods ; Male ; Female ; Middle Aged ; Aged ; *Respiration, Artificial/statistics & numerical data ; Cohort Studies ; Retrospective Studies ; Enteral Nutrition/methods/statistics & numerical data ; Adult ; Noninvasive Ventilation/methods ; Survival Analysis ; }, abstract = {OBJECTIVE: To analyze disease-modifying effects of percutaneous endoscopic gastrostomy (PEG) insertion for supporting nutrition, noninvasive ventilation (NIV), and tracheostomy-assisted ('invasive') ventilation (TIV) in amyotrophic lateral sclerosis (ALS).

METHODS: We retrospectively analyzed survival in a large population-based incident cohort that was prospectively followed up in our center. Analysis considered several known ALS-related prognostic variables.

RESULTS: In this population, PEG and NIV in multivariable analysis significantly correlated to survival as computed by disease onset to death/tracheostomy. NIV was associated with better survival while PEG was associated with reduced survival. Other independent prognostic factors were age at ALS onset, diagnostic delay, and flail arm/leg and pure upper motor neuron (PUMN) phenotypes. The length of survival after TIV was significantly associated with age at ALS onset (inverse correlation) whereas other variables did not. The length of survival after TIV correlated to age at ALS onset in such a way that each additional year of age at ALS onset decreased survival by about 0.7 months. Patients who underwent both TIV and NIV did not experience a better survival than those who underwent TIV alone.

CONCLUSION: The lack of effect of enteral nutrition on ALS survival probably reflected the timing of PEG insertion in patients with more severe disease. By contrast, patients who used mechanical ventilation had an increased overall survival compared with non-ventilated ones. The study also provided new information showing that the combined use of NIV and TIV did not may prolong ALS survival as compared to TIV alone.}, } @article {pmid38747109, year = {2024}, author = {Bender, J and Kojeku, T and Preece, E}, title = {Grading lumbar foraminal stenosis - Interrater agreement of radiologists and radiology trainees before and after education of a standardised grading scale.}, journal = {Journal of medical imaging and radiation oncology}, volume = {68}, number = {5}, pages = {511-515}, doi = {10.1111/1754-9485.13669}, pmid = {38747109}, issn = {1754-9485}, mesh = {Humans ; *Spinal Stenosis/diagnostic imaging ; *Lumbar Vertebrae/diagnostic imaging ; *Observer Variation ; *Magnetic Resonance Imaging/methods ; *Radiologists ; Severity of Illness Index ; Radiology/education ; Reproducibility of Results ; Clinical Competence ; Male ; }, abstract = {INTRODUCTION: Lumbar foraminal stenosis is a key contributor to low back pain. Imaging, particularly MRI, is commonly used in the assessment of foraminal stenosis, contributing to treatment planning. The adoption of a standardised grading system to try and improve inter-rater agreement is thought to be of importance. Our study aims to assess the variability of grading lumbar foraminal stenosis amongst reporting doctors, determine whether education about a validated grading scale increases agreement, and determine if these changes persist over time.

METHODS: A single-site study involving MRI reporting registrars/radiologists was performed. Participants were shown select MRI images and asked to grade the degree of stenosis in each on a 4-point scale. Subsequently, they were educated about Lee et al's grading system and asked to re-grade the cases 1 and 6 weeks later. The level of agreement was calculated using Gwet's AC1 coefficient and Krippendorff's Alpha.

RESULTS: The baseline level of agreement was substantial (AC1 = 0.71). This decreased to a moderate level of agreement post-intervention (AC1 = 0.575 at 1-week, P-value 0.033 and AC1 = 0.598 at 6 weeks, P-value 0.012). A grading of severe stenosis was 21% more likely 6 weeks post-education.

CONCLUSION: The baseline agreement at our institution was substantial, thought to be due to the single-centre nature of the study. Moderate agreement was achieved after education regarding the Lee et al.'s scale, in-line with other studies, with changes maintained at 6 weeks, showing retention of the scale parameters. Grading of severe stenosis was more common post intervention.}, } @article {pmid38747014, year = {2024}, author = {Gale, J and Aizenman, E}, title = {The physiological and pathophysiological roles of copper in the nervous system.}, journal = {The European journal of neuroscience}, volume = {60}, number = {1}, pages = {3505-3543}, pmid = {38747014}, issn = {1460-9568}, support = {R01 NS043277/NS/NINDS NIH HHS/United States ; 5T32AG021885/NH/NIH HHS/United States ; R56 NS043277/NS/NINDS NIH HHS/United States ; NS043277/NH/NIH HHS/United States ; T32 GM144300/GM/NIGMS NIH HHS/United States ; T32 AG021885/AG/NIA NIH HHS/United States ; }, mesh = {Humans ; *Copper/metabolism ; Animals ; Homeostasis/physiology ; Nervous System/metabolism ; }, abstract = {Copper is a critical trace element in biological systems due the vast number of essential enzymes that require the metal as a cofactor, including cytochrome c oxidase, superoxide dismutase and dopamine-β-hydroxylase. Due its key role in oxidative metabolism, antioxidant defence and neurotransmitter synthesis, copper is particularly important for neuronal development and proper neuronal function. Moreover, increasing evidence suggests that copper also serves important functions in synaptic and network activity, the regulation of circadian rhythms, and arousal. However, it is important to note that because of copper's ability to redox cycle and generate reactive species, cellular levels of the metal must be tightly regulated to meet cellular needs while avoiding copper-induced oxidative stress. Therefore, it is essential that the intricate system of copper transporters, exporters, copper chaperones and copper trafficking proteins function properly and in coordinate fashion. Indeed, disorders of copper metabolism such as Menkes disease and Wilson disease, as well as diseases linked to dysfunction of copper-requiring enzymes, such as SOD1-linked amyotrophic lateral sclerosis, demonstrate the dramatic neurological consequences of altered copper homeostasis. In this review, we explore the physiological importance of copper in the nervous system as well as pathologies related to improper copper handling.}, } @article {pmid38746326, year = {2025}, author = {Spencer, BE and Xie, SX and Ohm, DT and Elman, L and Quinn, CC and Amado, D and Baer, M and Lee, EB and Van Deerlin, VM and Dratch, L and Massimo, L and Irwin, DJ and McMillan, CT}, title = {Cumulative Incidence of Motor and Cognitive Features in the ALS-FTD Spectrum.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, doi = {10.1101/2024.04.30.24306638}, pmid = {38746326}, support = {K08 NS114106/NS/NINDS NIH HHS/United States ; }, abstract = {UNLABELLED: In frontotemporal degeneration (FTD) and amyotrophic lateral sclerosis (ALS), subsequent motor or cognitive-behavioral features, respectively, are associated with shorter survival. However, factors influencing subsequent feature development remain largely unexplored. In this study, we examined whether the presence of a C9orf72 expansion or the initial clinical syndrome was associated with increased risk of subsequent feature development in individuals with ALS and FTD. We performed a retrospective evaluation of the entire disease course of individuals with ALS and FTD who had neuropathological confirmation of TDP-43 proteinopathy at autopsy or a C9orf72 hexanucleotide repeat expansion. We examined the odds and hazard of subsequent feature development and assessed whether each was modified by the presence of a C9orf72 expansion or initial clinical syndrome. At autopsy, we evaluated the association between TDP-43 pathology burden in characteristic brain regions and features across the FTD-ALS spectrum. For individuals with ALS (n=168) and FTD (n=73), binary logistic regression revealed increased odds (OR=3.49[95% CI 1.64-7.80], p=0.002) for developing subsequent features in those with a C9orf72 expansion compared to those without and decreased odds (OR=0.25[95% CI 0.12-0.53], p<0.001) for developing subsequent features in those with an initial ALS clinical syndrome compared to those with an initial FTD clinical syndrome. Cox proportional hazard analyses revealed an increased hazard (HR=3.78[95% CI 1.86-7.65], p<0.001) for developing subsequent features in those with a C9orf72 expansion compared to those without. We observed a 94-month difference in the time after symptom onset of the initial clinical syndrome that a given person without a C9orf72 expansion reached the highest probability of developing subsequent features (0.12[95% CI (0.03-0.19], 113.00 months) and a person with a C9orf72 expansion surpassed that probability (0.13[95% CI 0.06-0.19], 19.00 months). Beyond C9orf72 expansion status, cox proportional hazard analyses revealed a decreased hazard (HR=0.48[95% CI 0.25-0.95], p=0.03) for developing subsequent features in those with an initial ALS clinical syndrome compared to those with an initial FTD clinical syndrome. Age at symptom onset and sex were not associated with development of subsequent features. The distribution of TDP-43 pathology across characteristic brain regions reflected both the initial clinical syndrome and subsequent features, with relatively preserved spinal cord only in FTD cases without subsequent motor features (p<0.0001) and relatively preserved neocortical regions only in ALS cases without subsequent cognitive-behavioral features (p<0.0001). These data highlight the need for clinician vigilance to detect the onset of subsequent motor and cognitive-behavioral features in patients carrying a C9orf72 expansion, regardless of initial clinical syndrome. C9orf72 clinical care can be enhanced through coordination between cognitive and neuromuscular clinics.

ABBREVIATED SUMMARY: Spencer et al. demonstrated both the presence of a C9orf72 expansion and the initial clinical syndrome modify risk of subsequent feature development in frontotemporal degeneration and amyotrophic lateral sclerosis, highlighting the need for clinician vigilance to detect the onset of subsequent motor and cognitive-behavioral features in this disease spectrum.}, } @article {pmid38745522, year = {2024}, author = {Mioshi, E and Grant, K and Flanagan, E and Heal, S and Copsey, H and Gould, RL and Hammond, M and Shepstone, L and Ashford, PA}, title = {An online intervention for carers to manage behavioral symptoms in motor neuron disease (MiNDToolkit): a randomized parallel multi-center feasibility trial.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {25}, number = {5-6}, pages = {506-516}, pmid = {38745522}, issn = {2167-9223}, mesh = {Humans ; *Motor Neuron Disease/psychology/therapy ; Male ; Female ; *Caregivers/psychology ; *Feasibility Studies ; Middle Aged ; Aged ; Behavioral Symptoms/etiology/therapy ; Adult ; }, abstract = {BACKGROUND: Evidence on management of behavioral symptoms in motor neuron disease (MND) is lacking. The MiNDToolkit, an online psychoeducational platform, supports carers dealing with behavioral symptoms (BehSymp). The study objectives were to ascertain recruitment and retention rates, carer and healthcare professional (HCP) use of the platform, and completion of online assessments, to inform a full-scale trial. Design: Randomized, parallel, multi-center, feasibility trial.

SETTING: England and Wales, across diverse MND services; recruitment from July/21 to November/22; last participant follow-up in March/23.

PARTICIPANTS: Carers of people with motor neuron disease (PwMND) with BehSymp, recruited through MND services. After confirming eligibility, participants completed screening and baseline assessments online via the MiNDToolkit platform and were randomized centrally in a 1:1 ratio to MiNDToolkit or control.

INTERVENTION: MiNDToolkit offered tailored modules to carers for the 3-month study period. Carers in the intervention group could receive additional support from MiNDToolkit trained HCPs. The control group was offered access to the intervention at the end of the study. Data were collected on platform usage and psychosocial variables.

MAIN OUTCOMES: One hundred and fifty-one carers from 11 sites were invited to join the study (letter, face-to-face); 30 were screened; 29 were randomized. Fifteen people were allocated to the control arm; 14 to intervention. Carers were mostly female; median age for was 62.5 (IQR: 58, 68; intervention) and 57 (IQR: 56, 70; controls). Study retention was high (24/29 = 82.76%); carers engaged with the platform on average 14 times (median (IQR):14.0 (10.0, 18.5)) during the study period.

CONCLUSION: The MiNDToolkit study was feasible and well accepted by carers and trained HCPs. A definitive trial is warranted.}, } @article {pmid38745521, year = {2024}, author = {Fernandez, A and Guenegou, L and Corcia, P and Bailly, N}, title = {The effect of social support on the emotional well-being of people with amyotrophic lateral sclerosis: Exploring the mediating role of spirituality.}, journal = {Palliative & supportive care}, volume = {}, number = {}, pages = {1-8}, doi = {10.1017/S1478951524000610}, pmid = {38745521}, issn = {1478-9523}, abstract = {OBJECTIVES: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that, so far, is considered always fatal. Treatments mainly consist in increasing survival and aim to improve the quality of life of people with ALS (pwALS). Social support and spirituality have been shown to play a key role in pwALS' quality of life. Our study explored it in depth by investigating the underlying mechanisms linking social support, spirituality, and emotional well-being.

METHODS: Thirty-six pwALS underwent a battery of tests evaluating emotional well-being (emotional well-being scale of the 40-item Amyotrophic Lateral Sclerosis Assessment Questionnaire), social support (6-item Social Support Questionnaire), and spiritual well-being (12-item Functional Assessment of Chronic Illness Therapy - Spiritual well-being). Our recruitment was web-based through the FILSLAN and the ARSLA websites as well as through Facebook® advertisements (ALS groups). Data were analyzed by Pearson correlation analysis and Process macro was used in an SPSS program to analyze the mediator variable effect.

RESULTS: Availability of social support, spiritual well-being, and 2 of its dimensions, i.e., meaning and peace, were positively correlated with emotional well-being. The mediational analyses showed that spiritual well-being, meaning, and peace act as mediators in the association between availability of social support and good emotional well-being.

SIGNIFICANCE OF RESULTS: Availability of social support and spirituality are essential for the emotional well-being of pwALS. Spirituality as a mediator between availability of social support and emotional well-being appears as real novel finding which could be explored further. Spiritual well-being, meaning, and peace appear as coping resources for pwALS. We provide practical guidance for professionals working with pwALS.}, } @article {pmid38745475, year = {2024}, author = {Katangwe-Chigamba, T and Flanagan, E and Mioshi, E}, title = {Implementation of the MiNDToolkit intervention for the management of behavioral symptoms in MND by healthcare professionals: a mixed-methods process evaluation.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {25}, number = {5-6}, pages = {496-505}, pmid = {38745475}, issn = {2167-9223}, mesh = {Humans ; *Health Personnel/psychology/education ; Male ; Female ; *Motor Neuron Disease/psychology/therapy ; *Caregivers/psychology ; Behavioral Symptoms/therapy/etiology ; Middle Aged ; Adult ; Surveys and Questionnaires ; Feasibility Studies ; }, abstract = {OBJECTIVE: MiNDToolkit is a novel psychoeducational intervention for carers to support management of behavioral symptoms in people living with motor neuron disease (PlwMND). Implementation of MiNDToolkit involves delivery of an online intervention to carers, which is reinforced by trained healthcare professionals (HCPs).

METHODS: A mixed-methods process evaluation of the MiNDToolkit feasibility trial was conducted, focusing on reinforcement of the intervention by HCPs. Quantitative data, descriptively analyzed, were included from platform analytics, questionnaire, and 10 semi-structured interviews with HCPs. Interviews were transcribed verbatim; data were inductively analyzed using Reflective Thematic Analysis.

RESULTS: The MiNDToolkit training and platform is a beneficial and acceptable resource for HCPs with potential to increase knowledge and confidence in identifying and managing behavioral symptoms in MND. Implementation barriers included HCPs' perceptions that highlighting behavior changes would be burdensome to carers and assumptions that carers would take the initiative to ask for support from clinicians. Degree of intervention reinforcement varied, with most HCPs delegating intervention delivery solely to the online platform.

CONCLUSIONS: Implementation of the MiNDToolkit was viewed to be feasible and the platform thought to increase accessibility of support to carers. The flexible approach to delivery (online platform and optional HCP reinforcement) is acceptable as an intervention for supporting carers of PlwMND with behavioral symptoms. However, MiNDToolkit should not negate HCP involvement in providing medical and practical information to PlwMND and families. Future research should explore ways to incorporate support for carers in the management of PlwMND alongside standard care, alongside tools such as the MiNDToolkit.}, } @article {pmid38745425, year = {2024}, author = {Nona, RJ and Henderson, RD and McCombe, PA}, title = {Neutrophil-to-lymphocyte ratio at diagnosis as a biomarker for survival of amyotrophic lateral sclerosis.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {25}, number = {5-6}, pages = {452-464}, doi = {10.1080/21678421.2024.2351187}, pmid = {38745425}, issn = {2167-9223}, mesh = {*Amyotrophic Lateral Sclerosis/blood/diagnosis/mortality ; Humans ; *Neutrophils ; *Lymphocytes ; Female ; Male ; Biomarkers/blood ; Middle Aged ; Aged ; }, abstract = {INTRODUCTION: The neutrophil-to-lymphocyte ratio (NLR) has previously been reported to be associated with survival in ALS. To provide further information about the role of NLR as a biomarker in ALS, we performed a systematic review, analyzed data from our local cohort of ALS subjects and performed a meta-analysis.

METHODS: (1) The systematic review used established methods. (2) Using data from our cohort of subjects, we analyzed the association of NLR with survival. (3) Meta-analysis was performed using previous studies and our local data.

RESULTS: (1) In the systematic review, higher NLR was associated with shorter survival in all studies. (2) In our subjects, survival was significantly shorter in patients in the highest NLR groups. (3) Meta-analysis showed subjects with highest NLR tertile or with NLR >3 had significantly shorter survival than other subjects.

DISCUSSION: This study supports NLR as a biomarker in ALS; high NLR is associated with poor survival.}, } @article {pmid38744216, year = {2024}, author = {Trivedi, RR and Archambault, AS and Pavlak, C and Gastaldi, M and Cantoni, C and Ghezzi, L and Cross, AH and Miller, TM and Wu, GF}, title = {Prevalence of anti-myelin oligodendrocyte glycoprotein antibodies across neuroinflammatory and neurodegenerative diseases.}, journal = {Journal of the neurological sciences}, volume = {461}, number = {}, pages = {123041}, doi = {10.1016/j.jns.2024.123041}, pmid = {38744216}, issn = {1878-5883}, support = {I01 CX002383/CX/CSRD VA/United States ; }, mesh = {*Myelin-Oligodendrocyte Glycoprotein/immunology ; Humans ; *Autoantibodies/blood ; Female ; Male ; Middle Aged ; *Amyotrophic Lateral Sclerosis/blood/immunology/diagnosis ; *Immunoglobulin G/blood ; Neurodegenerative Diseases/immunology/blood/diagnosis ; Aged ; Neuroinflammatory Diseases/immunology/blood ; Adult ; Multiple Sclerosis/immunology/blood ; Animals ; }, abstract = {Inflammatory central nervous system (CNS) diseases, such as multiple sclerosis (MS) and myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD), are characterized by humoral immune abnormalities. Anti-MOG antibodies are not specific to MOGAD, with their presence described in MS. Autoantibodies may also be present and play a role in various neurodegenerative diseases. Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease driven by motor neuron dysfunction. While immune involvement in ALS has been recognized, the presence of antibodies targeting CNS myelin antigens has not been established. We aimed to establish a live cell-based assay for quantification of serum anti-MOG IgG1 in patients with CNS diseases, including MS and ALS. In total, 771 serum samples from the John L. Trotter MS Center and the Northeast ALS Consortium were examined using a live cell-based assay for detection of anti-MOG IgG1. Samples from three cohorts were tested in blinded fashion: healthy control (HC) subjects, patients with clinically diagnosed MOGAD, and an experimental group of ALS and MS patients. All samples from established MOGAD cases were positive for anti-MOG antibodies, while all HC samples were negative. Anti-MOG IgG1 was detected in 65 of 658 samples (9.9%) from MS subjects and 4 of 108 (3.7%) samples from ALS subjects. The presence of serum anti-MOG IgG1 in MS and ALS patients raises questions about the contribution of these antibodies to disease pathophysiology as well as accuracy of diagnostic approaches for CNS inflammatory diseases.}, } @article {pmid38743595, year = {2024}, author = {Klose, V and Jesse, S and Lewerenz, J and Kassubek, J and Dorst, J and Rosenbohm, A and Nagel, G and Wernecke, D and Roselli, F and Tumani, H and Ludolph, AC}, title = {Blood-CSF barrier integrity in amyotrophic lateral sclerosis.}, journal = {Brain : a journal of neurology}, volume = {147}, number = {12}, pages = {4254-4264}, doi = {10.1093/brain/awae144}, pmid = {38743595}, issn = {1460-2156}, support = {443642953//Deutsche Zentrum für Neurodegenerative Erkrankungen (DZNE)/ ; 251293561//Danger Response, Disturbance Factors and Regenerative Potential after Acute Trauma/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis ; Male ; Female ; Middle Aged ; Aged ; *Blood-Brain Barrier/metabolism ; Adult ; Albumins/metabolism ; Aged, 80 and over ; Cohort Studies ; }, abstract = {The integrity of the blood-CSF barrier plays a major role in inflammation, but also in shielding the CNS from external and systemic-potentially toxic-factors. Here we report results of measurements of the albumin quotient-which is thought to mirror the integrity of the blood-CSF barrier-in 1059 patients with amyotrophic lateral sclerosis. The results were compared with groups of patients suffering from Alzheimer's disease, facial palsy and tension headache. The albumin quotient, an accepted measure of the blood-CSF barrier integrity, was not significantly different from control populations. In addition, we found that the albumin quotient correlated with survival of the patients; this effect was mainly driven by male patients and influenced by age, body mass index and diabetes mellitus. We conclude that the blood-CSF barrier is intact in this large cohort of patients with amyotrophic lateral sclerosis and that the albumin quotient correlates with survival. Whether this is important for the pathogenesis of the disease, requires mechanistic studies.}, } @article {pmid38743390, year = {2024}, author = {Vignolo, M and Zuccarino, R and Truffelli, R and Gemelli, C and Giove, E and Ferraro, PM and Manunza, D and Trinchero, C and Cipollina, I and Lungu, M and Lizio, A and Gragnano, G and Cabona, C and Pardini, M and Caponnetto, C and Rao, F}, title = {Dog-assisted physiotherapy in amyotrophic lateral sclerosis: a randomized controlled pilot study.}, journal = {European journal of physical and rehabilitation medicine}, volume = {60}, number = {3}, pages = {470-476}, pmid = {38743390}, issn = {1973-9095}, mesh = {Humans ; Pilot Projects ; *Amyotrophic Lateral Sclerosis/rehabilitation ; Male ; Female ; Middle Aged ; *Animal Assisted Therapy/methods ; Aged ; *Physical Therapy Modalities ; Animals ; Dogs ; Treatment Outcome ; }, abstract = {BACKGROUND: Animal-assisted therapy (AAT) is an intervention in which the animal acts as a co-therapist. It has been mainly used in the context of patients with dementia, showing positive effects on psychological symptoms, but its potential as a physiotherapy treatment for patients with neuromuscular disorders, amyotrophic lateral sclerosis (ALS) in particular, has not yet been investigated.

AIM: The aim of the study was to evaluate the impact of AAT, specifically of dog-assisted therapy, on motor functions and psychological status in patients with ALS.

DESIGN: This study was a randomized controlled pilot study.

SETTING: The study was carried out at the Rehabilitation Unit NEuroMuscular Omnicenter (NEMO) of Arenzano, Genoa.

POPULATION: Sixty hospitalized ALS patients were enrolled.

METHODS: All patients ran a regular two-weeks neurorehabilitation program twice a day. For three days a week, in place of the morning traditional treatment, the AAT group performed a rehabilitation session with a simultaneous interaction with the therapy-dog, while the control group performed a traditional rehabilitation session. The outcome measures were the Timed Up and Go Test, the Short Physical Performance Battery (SPPB), the Six Minutes Walk Test, the Ten Meters walking Test and the Hospital Anxiety and Depression Scale.

RESULTS: Both groups showed an amelioration in motor scales. However, SPPB subscales as well as HADS scores showed a statistically significant improvement only in the AAT group (P values from <0.0001 to 0.0004). Additionally, across almost all motor and psychological measures, post-treatments values were significantly better for the AAT group (P values from <0.0001 to 0.01).

CONCLUSIONS: The obtained results not only suggest that AAT is comparable to traditional physiotherapy treatments, but also evidence that this type of treatment has greater beneficial effects on motor and psychological symptoms in patients with ALS.

This study provides first evidence that AAT is a powerful rehabilitation strategy in patients with ALS, improving both motor and psychological symptoms, and therefore possibly ameliorating quality of life.}, } @article {pmid38743164, year = {2024}, author = {Zoccolella, S and Milella, G and Giugno, A and Filardi, M and D'Errico, E and Tamburrino, L and Devitofrancesco, V and Damato, R and Piomboni, F and Misceo, S and Logroscino, G}, title = {Nerve conduction study on the split-hand plus index in Amyotrophic lateral sclerosis: correlations with lower motor neuron impairment.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {45}, number = {10}, pages = {4863-4870}, pmid = {38743164}, issn = {1590-3478}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology/diagnosis ; Male ; Female ; Middle Aged ; *Neural Conduction/physiology ; Aged ; Case-Control Studies ; *Motor Neurons/physiology ; Hand/physiopathology ; Prospective Studies ; Action Potentials/physiology ; Median Nerve/physiopathology ; Adult ; Nerve Conduction Studies ; }, abstract = {INTRODUCTION: In the arms of patients with Amyotrophic lateral sclerosis (ALS) two peculiar patterns of dissociated muscular atrophy have been described: the split-hand sign (with predominant atrophy of the lateral aspect of the hand, compared to hypothenar eminence) and the split-hand-plus sign (SHPS), a predominant abductor pollicis brevis (ABP) atrophy with sparing of flexor pollicis longus (FPL).

AIMS: In this case-control study, we evaluated the diagnostic utility of a neurophysiological indicator of SHPS and assessed its association with clinical features.

METHODS: We prospectively studied 59 incident ALS patients, 61 patients with ALS-mimic disorders (OND) and 61 non-neurological controls (NNCs). ABP and FPL compound muscle action potentials (CMAP) amplitudes were obtained by supramaximal stimulation of median nerve at elbow. Split-hand plus index (SHPI) was calculated according to the formula: APB-CMAP/FPL-CMAP.

RESULTS: SHPI was significantly lower in ALS compared to OND patients and NNCs (p < 0.0001). SHPI value < 1 was observed in 2% of NNCs and 9% of OND patients and demonstrated an accuracy of 71% in differentiating ALS from OND and an accuracy of 74% in differentiating ALS from NNC. SHPI was associated with higher LMN score, and higher disease severity as quantified by the ALSFRS-r.

CONCLUSION: Our results indicate that SHPI is a reliable indicator to distinguish ALS patients from ONDs and NNCs. SHPI was significantly associated to the degree of lower motor neuron impairment but showed no association with upper motoneuron impairment.}, } @article {pmid38742757, year = {2024}, author = {Shephard, VK and Brown, ML and Thompson, BA and Harpur, A and McAlary, L}, title = {Rapid classification of a novel ALS-causing I149S variant in superoxide dismutase-1.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {25}, number = {5-6}, pages = {608-614}, doi = {10.1080/21678421.2024.2351177}, pmid = {38742757}, issn = {2167-9223}, mesh = {*Amyotrophic Lateral Sclerosis/genetics ; Humans ; *Superoxide Dismutase-1/genetics ; Middle Aged ; Male ; Female ; Mutation/genetics ; }, abstract = {Variants of the oxygen free radical scavenging enzyme superoxide dismutase-1 (SOD1) are associated with the neurodegenerative disease amyotrophic lateral sclerosis (ALS). These variants occur in roughly 20% of familial ALS cases, and 1% of sporadic ALS cases. Here, we identified a novel SOD1 variant in a patient in their 50s who presented with movement deficiencies and neuropsychiatric features. The variant was heterozygous and resulted in the isoleucine at position 149 being substituted with a serine (I149S). In silico analysis predicted the variant to be destabilizing to the SOD1 protein structure. Expression of the SOD1[I149S] variant with a C-terminal EGFP tag in neuronal-like NSC-34 cells resulted in extensive inclusion formation and reduced cell viability. Immunoblotting revealed that the intramolecular disulphide between Cys57 and Cys146 was fully reduced for SOD1[I149S]. Furthermore, SOD1[I149S] was highly susceptible to proteolytic digestion, suggesting a large degree of instability to the protein fold. Finally, fluorescence correlation spectroscopy and native-PAGE of cell lysates showed that SOD1[I149S] was monomeric in solution in comparison to the dimeric SOD1[WT]. This experimental data was obtained within 3 months and resulted in the rapid re-classification of the variant from a variant of unknown significance (VUS) to a clinically actionable likely pathogenic variant.}, } @article {pmid38742544, year = {2024}, author = {Donohue, C and Vasilopoulos, T and Wymer, JP and Plowman, EK}, title = {Relationship between pulmonary, cough, and swallowing functions in individuals with amyotrophic lateral sclerosis.}, journal = {Muscle & nerve}, volume = {70}, number = {1}, pages = {140-147}, pmid = {38742544}, issn = {1097-4598}, support = {//Nancy McEwans Wilkins Fellowship for ALS Research Fund/ ; 1R01NS100859/NS/NINDS NIH HHS/United States ; R01 NS100859/NS/NINDS NIH HHS/United States ; //ALS Association/ ; //University of Florida McKnight Brain Institute and BREATHING Research and Therapeutics Center/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology/complications ; Male ; *Cough/physiopathology/etiology ; Female ; Middle Aged ; Aged ; *Deglutition/physiology ; *Deglutition Disorders/physiopathology/etiology ; Vital Capacity/physiology ; Adult ; Lung/physiopathology/diagnostic imaging ; Fluoroscopy ; Respiratory Function Tests ; }, abstract = {INTRODUCTION/AIMS: Evaluations of pulmonary, cough, and swallow function are frequently performed to assess disease progression in amyotrophic lateral sclerosis (ALS), yet the relationship between these functions remains unknown. We therefore aimed to determine relationships between these measures in individuals with ALS.

METHODS: One hundred individuals with ALS underwent standardized tests: forced vital capacity (FVC), maximum expiratory/inspiratory pressure (MEP, MIP), voluntary cough peak expiratory flow (PEF), and videofluoroscopic swallow evaluation (VF). Duplicate raters completed independent, blinded ratings using the Dynamic Imaging Grade of Swallowing Toxicity (DIGEST) scale. Descriptives, Spearman's Rho correlations, Kruskal-Wallis analyses, and Pearson's chi-squared tests were completed.

RESULTS: Mean and standard deviation across pulmonary and cough measures were FVC: 74.2% predicted (± 22.6), MEP: 91.6 cmH2O (± 46.4), MIP cmH2O: 61.1 (± 28.9), voluntary PEF: 352.7 L/min (± 141.6). DIGEST grades included: 0 (normal swallowing): 31%, 1 (mild dysphagia): 48%, 2 (moderate dysphagia): 10%, 3 (severe dysphagia): 10%, and 4 (life-threatening dysphagia): 1%. Positive correlations were observed: MEP-MIP: r = .76, MIP-PEF: r = .68, MEP-PEF: r = .61, MIP-FVC: r = .60, PEF-FVC: r = .49, and MEP-FVC: r = .46, p < .0001. MEP (p = .009) and PEF (p = .04) differed across DIGEST safety grades. Post hoc analyses revealed significant between group differences in MEP and PEF across DIGEST safety grades 0 versus 1 and grades 0 versus 3, (p < .05).

DISCUSSION: In this cohort of individuals with ALS, pulmonary function, and voluntary cough were associated. Expiratory metrics (MEP, PEF) were diminished in individuals with unsafe swallowing, increasing their risk for effectively defending the airway.}, } @article {pmid38742276, year = {2024}, author = {Cheung, SW and Bhavnani, E and Simmons, DG and Bellingham, MC and Noakes, PG}, title = {Perineuronal nets are phagocytosed by MMP-9 expressing microglia and astrocytes in the SOD1[G93A] ALS mouse model.}, journal = {Neuropathology and applied neurobiology}, volume = {50}, number = {3}, pages = {e12982}, doi = {10.1111/nan.12982}, pmid = {38742276}, issn = {1365-2990}, support = {GIC1842//Motor Neuron Disease Research Australia/ ; I2326//Motor Neuron Disease Research Australia/ ; GIV1842//Motor Neuron Disease Research Australia/ ; IG2326//Motor Neuron Disease Research Australia/ ; 1188169//National Health & Medical Research Council Australia/ ; }, mesh = {Animals ; Mice ; *Amyotrophic Lateral Sclerosis/pathology/metabolism/genetics ; *Astrocytes/metabolism/pathology ; Disease Models, Animal ; Extracellular Matrix/metabolism/pathology ; *Matrix Metalloproteinase 9/metabolism ; Mice, Transgenic ; *Microglia/metabolism/pathology ; Motor Neurons/pathology/metabolism ; *Phagocytosis/physiology ; *Superoxide Dismutase-1/genetics/metabolism ; }, abstract = {AIMS: Perineuronal nets (PNNs) are an extracellular matrix structure that encases excitable neurons. PNNs play a role in neuroprotection against oxidative stress. Oxidative stress within motor neurons can trigger neuronal death, which has been implicated in amyotrophic lateral sclerosis (ALS). We investigated the spatio-temporal timeline of PNN breakdown and the contributing cellular factors in the SOD1[G93A] strain, a fast-onset ALS mouse model.

METHODS: This was conducted at the presymptomatic (P30), onset (P70), mid-stage (P130), and end-stage disease (P150) using immunofluorescent microscopy, as this characterisation has not been conducted in the SOD1[G93A] strain.

RESULTS: We observed a significant breakdown of PNNs around α-motor neurons in the ventral horn of onset and mid-stage disease SOD1[G93A] mice compared with wild-type controls. This was observed with increased numbers of microglia expressing matrix metallopeptidase-9 (MMP-9), an endopeptidase that degrades PNNs. Microglia also engulfed PNN components in the SOD1[G93A] mouse. Further increases in microglia and astrocyte number, MMP-9 expression, and engulfment of PNN components by glia were observed in mid-stage SOD1[G93A] mice. This was observed with increased expression of fractalkine, a signal for microglia engulfment, within α-motor neurons of SOD1[G93A] mice. Following PNN breakdown, α-motor neurons of onset and mid-stage SOD1[G93A] mice showed increased expression of 3-nitrotyrosine, a marker for protein oxidation, which could render them vulnerable to death.

CONCLUSIONS: Our observations suggest that increased numbers of MMP-9 expressing glia and their subsequent engulfment of PNNs around α-motor neurons render these neurons sensitive to oxidative damage and eventual death in the SOD1[G93A] ALS model mouse.}, } @article {pmid38741492, year = {2024}, author = {Kanda, S and Kanda, T}, title = {[Multifocal Motor Neuropathy].}, journal = {Brain and nerve = Shinkei kenkyu no shinpo}, volume = {76}, number = {5}, pages = {526-533}, doi = {10.11477/mf.1416202639}, pmid = {38741492}, issn = {1881-6096}, mesh = {Humans ; *Polyneuropathies/physiopathology/diagnosis ; Immunoglobulins, Intravenous/therapeutic use/administration & dosage ; }, abstract = {Multifocal motor neuropathy (MMN), an acquired chronic progressive immune-mediated motor neuropathy, is characterized by asymmetrical distal upper limb muscle weakness and muscle atrophy without sensory impairment. Differentiation from amyotrophic lateral sclerosis is usually challenging, and electrophysiological studies show multifocal conduction blocks. Immunoglobulin (Ig)M GM1 antibodies are detected in approximately 50% of patients. In contrast to chronic inflammatory demyelinating polyneuropathy, corticosteroids are ineffective for management of MMN, and IVIg is the sole established treatment.}, } @article {pmid38741111, year = {2024}, author = {Maresova, P and Rezny, L and Bauer, P and Valko, M and Kuca, K}, title = {Nonpharmacological intervention therapies for dementia: potential break-even intervention price and savings for selected risk factors in the European healthcare system.}, journal = {BMC public health}, volume = {24}, number = {1}, pages = {1293}, pmid = {38741111}, issn = {1471-2458}, support = {ERDF No. CZ.02.1.01/0.0/0.0/18_069/0010054-IT4Neuro(degeneration)//Ministry of Education Youth and Sports/ ; Excellence 2022//UHK FIM/ ; }, mesh = {Humans ; *Dementia/economics/epidemiology/prevention & control ; Risk Factors ; Europe/epidemiology ; Cost Savings ; Aged ; Health Care Costs/statistics & numerical data ; Models, Theoretical ; Male ; Female ; Prevalence ; Aged, 80 and over ; Middle Aged ; }, abstract = {BACKGROUND: New effective treatments for dementia are lacking, and early prevention focusing on risk factors of dementia is important. Non-pharmacological intervention therapies aimed at these factors may provide a valuable tool for reducing the incidence of dementia. This study focused on the development of a mathematical model to predict the number of individuals with neurodegenerative diseases, specifically Alzheimer's disease, Parkinson's disease, vascular dementia, and amyotrophic lateral sclerosis. Scenarios for non-pharmacological intervention therapies based on risk factor reduction were also assessed. The estimated total costs and potential cost savings from societal were included.

METHODS: Based on demographic and financial data from the EU, a mathematical model was developed to predict the prevalence and resulting care costs of neurodegenerative diseases in the population. Each disease (Alzheimer's disease, Parkinson's disease, vascular dementia, and amyotrophic lateral sclerosis) used parameters that included prevalence, incidence, and death risk ratio, and the simulation is related to the age of the cohort and the disease stage.

RESULTS: A replicable simulation for predicting the prevalence and resulting cost of care for neurodegenerative diseases in the population exhibited an increase in treatment costs from 267 billion EUR in 2021 to 528 billion EUR by 2050 in the EU alone. Scenarios related to the reduction of the prevalence of dementia by up to 20% per decade led to total discounted treatment cost savings of up to 558 billion EUR.

CONCLUSION: The model indicates the magnitude of the financial burden placed on EU healthcare systems due to the growth in the population prevalence of neurodegenerative diseases in the coming decades. Lifestyle interventions based on reducing the most common risk factors could serve as a prevention strategy to reduce the incidence of dementia with substantial cost-savings potential. These findings could support the implementation of public health approaches throughout life to ultimately prevent premature mortality and promote a healthier and more active lifestyle in older individuals.}, } @article {pmid38739991, year = {2024}, author = {Li, X and Liu, N and Wu, D and Li, SC and Wang, Q and Zhang, DW and Song, LL and Huang, M and Chen, X and Li, W}, title = {Hippocampal transcriptomic analyses reveal the potential antiapoptotic mechanism of a novel anticonvulsant agent Q808 on pentylenetetrazol-induced epilepsy in rats.}, journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie}, volume = {175}, number = {}, pages = {116746}, doi = {10.1016/j.biopha.2024.116746}, pmid = {38739991}, issn = {1950-6007}, mesh = {Animals ; *Pentylenetetrazole ; *Hippocampus/drug effects/metabolism/pathology ; *Apoptosis/drug effects ; *Anticonvulsants/pharmacology ; Male ; *Transcriptome/drug effects ; *Epilepsy/drug therapy/chemically induced/genetics ; *Gene Expression Profiling/methods ; Rats ; *Rats, Sprague-Dawley ; Disease Models, Animal ; Neurons/drug effects/metabolism/pathology ; Seizures/chemically induced/genetics/drug therapy ; }, abstract = {Brain apoptosis is one of the main causes of epileptogenesis. The antiapoptotic effect and potential mechanism of Q808, an innovative anticonvulsant chemical, have never been reported. In this study, the seizure stage and latency to reach stage 2 of pentylenetetrazol (PTZ) seizure rat model treated with Q808 were investigated. The morphological change and neuronal apoptosis in the hippocampus were detected by hematoxylin and eosin (HE) and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) staining, respectively. The hippocampal transcriptomic changes were observed using RNA sequencing (RNA-seq). The expression levels of hub genes were verified by quantitative reverse-transcription PCR (qRT-PCR). Results revealed that Q808 could allay the seizure score and prolong the stage 2 latency in seizure rats. The morphological changes of neurons and the number of apoptotic cells in the DG area were diminished by Q808 treatment. RNA-seq analysis revealed eight hub genes, including Map2k3, Nfs1, Chchd4, Hdac6, Siglec5, Slc35d3, Entpd1, and LOC103690108, and nine hub pathways among the control, PTZ, and Q808 groups. Hub gene Nfs1 was involved in the hub pathway sulfur relay system, and Map2k3 was involved in the eight remaining hub pathways, including Amyotrophic lateral sclerosis, Cellular senescence, Fc epsilon RI signaling pathway, GnRH signaling pathway, Influenza A, Rap1 signaling pathway, TNF signaling pathway, and Toll-like receptor signaling pathway. qRT-PCR confirmed that the mRNA levels of these hub genes were consistent with the RNA-seq results. Our findings might contribute to further studies exploring the new apoptosis mechanism and actions of Q808.}, } @article {pmid38739934, year = {2024}, author = {Xin, J and Huang, S and Wen, J and Li, Y and Li, A and Satyanarayanan, SK and Yao, X and Su, H}, title = {Drug Screening and Validation Targeting TDP-43 Proteinopathy for Amyotrophic Lateral Sclerosis.}, journal = {Aging and disease}, volume = {16}, number = {2}, pages = {693-713}, pmid = {38739934}, issn = {2152-5250}, mesh = {*Amyotrophic Lateral Sclerosis/drug therapy/metabolism ; Humans ; *TDP-43 Proteinopathies/drug therapy/metabolism ; *DNA-Binding Proteins/metabolism ; Animals ; Drug Evaluation, Preclinical/methods ; Drug Discovery/methods ; }, abstract = {Amyotrophic lateral sclerosis (ALS) stands as a rare, yet severely debilitating disorder marked by the deterioration of motor neurons (MNs) within the brain and spinal cord, which is accompanied by degenerated corticobulbar/corticospinal tracts and denervation in skeletal muscles. Despite ongoing research efforts, ALS remains incurable, attributed to its intricate pathogenic mechanisms. A notable feature in the pathology of ALS is the prevalence of TAR DNA-binding protein 43 (TDP-43) proteinopathy, detected in approximately 97% of ALS cases, underscoring its significance in the disease's progression. As a result, strategies targeting the aberrant TDP-43 protein have garnered attention as a potential avenue for ALS therapy. This review delves into the existing drug screening systems aimed at TDP-43 proteinopathy and the models employed for drug efficacy validation. It also explores the hurdles encountered in the quest to develop potent medications against TDP-43 proteinopathy, offering insights into the intricacies of drug discovery and development for ALS. Through this comprehensive analysis, the review sheds light on the critical aspects of identifying and advancing therapeutic solutions for ALS.}, } @article {pmid38739752, year = {2024}, author = {Droppelmann, CA and Campos-Melo, D and Noches, V and McLellan, C and Szabla, R and Lyons, TA and Amzil, H and Withers, B and Kaplanis, B and Sonkar, KS and Simon, A and Buratti, E and Junop, M and Kramer, JM and Strong, MJ}, title = {Mitigation of TDP-43 toxic phenotype by an RGNEF fragment in amyotrophic lateral sclerosis models.}, journal = {Brain : a journal of neurology}, volume = {147}, number = {6}, pages = {2053-2068}, pmid = {38739752}, issn = {1460-2156}, support = {P40 OD018537/OD/NIH HHS/United States ; //Temerty Family Foundation/ ; /CAPMC/CIHR/Canada ; }, mesh = {Animals ; *Amyotrophic Lateral Sclerosis/metabolism/genetics/pathology ; *DNA-Binding Proteins/metabolism/genetics ; Mice ; Humans ; *Disease Models, Animal ; *Guanine Nucleotide Exchange Factors/metabolism/genetics ; *Phenotype ; Drosophila ; Mice, Transgenic ; Drosophila Proteins/genetics/metabolism ; Male ; }, abstract = {Aggregation of the RNA-binding protein TAR DNA binding protein (TDP-43) is a hallmark of TDP-proteinopathies including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). As TDP-43 aggregation and dysregulation are causative of neuronal death, there is a special interest in targeting this protein as a therapeutic approach. Previously, we found that TDP-43 extensively co-aggregated with the dual function protein GEF (guanine exchange factor) and RNA-binding protein rho guanine nucleotide exchange factor (RGNEF) in ALS patients. Here, we show that an N-terminal fragment of RGNEF (NF242) interacts directly with the RNA recognition motifs of TDP-43 competing with RNA and that the IPT/TIG domain of NF242 is essential for this interaction. Genetic expression of NF242 in a fruit fly ALS model overexpressing TDP-43 suppressed the neuropathological phenotype increasing lifespan, abolishing motor defects and preventing neurodegeneration. Intracerebroventricular injections of AAV9/NF242 in a severe TDP-43 murine model (rNLS8) improved lifespan and motor phenotype, and decreased neuroinflammation markers. Our results demonstrate an innovative way to target TDP-43 proteinopathies using a protein fragment with a strong affinity for TDP-43 aggregates and a mechanism that includes competition with RNA sequestration, suggesting a promising therapeutic strategy for TDP-43 proteinopathies such as ALS and FTD.}, } @article {pmid38738747, year = {2024}, author = {de Araújo, CM and de Alcântara, C and Alencar, MA and da Gama, NAS and Cruzeiro, MM and França, MC and Jaeger, A and Camargos, ST and Machado, TH and de Souza, LC}, title = {Language impairment in sporadic and familial (type 8) amyotrophic lateral sclerosis: A comparative study.}, journal = {Muscle & nerve}, volume = {70}, number = {1}, pages = {130-139}, doi = {10.1002/mus.28109}, pmid = {38738747}, issn = {1097-4598}, support = {//Brazilian National Council for Scientific and Technological Development (CNPq)/ ; 001//CAPES/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/diagnosis/physiopathology ; Male ; Female ; Middle Aged ; Aged ; Language Disorders/etiology/diagnosis ; Adult ; Neuropsychological Tests ; Language Tests ; }, abstract = {INTRODUCTION/AIMS: Language is frequently affected in patients with sporadic amyotrophic lateral sclerosis (sALS), with reduced performance in naming, syntactic comprehension, grammatical expression, and orthographic processing. However, the language profile of patients with familial type 8 ALS (ALS8), linked to p.P56S VAPB mutation, remains unclear. We investigated language in patients with ALS8 by examining their auditory comprehension and verbal production.

METHODS: We included three groups of participants: (1) patients with sALS (n = 20), (2) patients with familial ALS8 (n = 22), and (3) healthy controls (n = 21). The groups were matched for age, sex, and education level. All participants underwent a comprehensive language battery, including the Boston Diagnostic Aphasia Examination, the reduced Token test, letter fluency, categorical fluency (animals), word definition from the Cambridge Semantic Memory Research Battery, and a narrative discourse analysis. Participants also were evaluated using Addenbrooke's Cognitive Exam-Revised Version, the Hospital Anxiety and Depression Scale, and the ALS Functional Rating Scale-Revised.

RESULTS: Compared to controls, sALS and ALS8 patients had impaired performance on oral (syntactic and phonological processing) comprehension and inappropriate discourse cohesion. sALS and ALS8 did not differ in any language measure. There was no correlation between language scores and functional and psychiatric scales.

DISCUSSION: ALS8 patients exhibit language deficits that are independent of motor features. These findings are consistent with the current evidence suggesting that ALS8 has prominent non-motor features.}, } @article {pmid38738727, year = {2025}, author = {Bhushan, B and Singh, K and Kumar, S and Bhardwaj, A}, title = {Advancements in CRISPR-Based Therapies for Genetic Modulation in Neurodegenerative Disorders.}, journal = {Current gene therapy}, volume = {25}, number = {1}, pages = {34-45}, pmid = {38738727}, issn = {1875-5631}, mesh = {Humans ; *Neurodegenerative Diseases/therapy/genetics ; *Genetic Therapy/methods ; *CRISPR-Cas Systems/genetics ; *Gene Editing/methods ; Clustered Regularly Interspaced Short Palindromic Repeats/genetics ; Amyotrophic Lateral Sclerosis/therapy/genetics ; Parkinson Disease/therapy/genetics ; Mutation ; Huntington Disease/therapy/genetics ; }, abstract = {Neurodegenerative disorders pose significant challenges in the realm of healthcare, as these conditions manifest in complex, multifaceted ways, often attributed to genetic anomalies. With the emergence of CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) technology, a new frontier has been unveiled in the quest for targeted, precise genetic manipulation. This abstract explores the recent advancements and potential applications of CRISPR-based therapies in addressing genetic components contributing to various neurodegenerative disorders. The review delves into the foundational principles of CRISPR technology, highlighting its unparalleled ability to edit genetic sequences with unprecedented precision. In addition, it talks about the latest progress in using CRISPR to target specific genetic mutations linked to neurodegenerative diseases like Huntington's disease, Alzheimer's disease, amyotrophic lateral sclerosis (ALS), and Parkinson's disease. It talks about the most important studies and trials that show how well and safely CRISPR-based therapies work. This shows how this technology can change genetic variants that cause diseases. Notably, the discussion emphasizes the challenges and ethical considerations associated with the implementation of CRISPR in clinical settings, including off-target effects, delivery methods, and long-term implications. Furthermore, the article explores the prospects and potential hurdles in the widespread application of CRISPR technology for treating neurodegenerative disorders. It touches upon the need for continued research, improved delivery mechanisms, and ethical frameworks to ensure responsible and equitable access to these groundbreaking therapies.}, } @article {pmid38738637, year = {2024}, author = {Błaszczyk, L and Ryczek, M and Das, B and Mateja-Pluta, M and Bejger, M and Śliwiak, J and Nakatani, K and Kiliszek, A}, title = {Antisense RNA C9orf72 hexanucleotide repeat associated with amyotrophic lateral sclerosis and frontotemporal dementia forms a triplex-like structure and binds small synthetic ligand.}, journal = {Nucleic acids research}, volume = {52}, number = {11}, pages = {6707-6717}, pmid = {38738637}, issn = {1362-4962}, support = {UMO-2022/45/B/NZ7/03543//National Science Centre/ ; 22H00351//Japan Society for the Promotion of Science/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/genetics/metabolism ; *Frontotemporal Dementia/genetics/metabolism ; *C9orf72 Protein/genetics/metabolism ; Humans ; Ligands ; RNA, Antisense/genetics/chemistry/metabolism ; Nucleic Acid Conformation ; DNA Repeat Expansion/genetics ; Crystallography, X-Ray ; Models, Molecular ; }, abstract = {The abnormal expansion of GGGGCC/GGCCCC hexanucleotide repeats (HR) in C9orf72 is associated with amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Structural polymorphisms of HR result in the multifactorial pathomechanism of ALS/FTD. Consequently, many ongoing studies are focused at developing therapies targeting pathogenic HR RNA. One of them involves small molecules blocking sequestration of important proteins, preventing formation of toxic nuclear foci. However, rational design of potential therapeutics is hindered by limited number of structural studies of RNA-ligand complexes. We determined the crystal structure of antisense HR RNA in complex with ANP77 ligand (1.1 Å resolution) and in the free form (0.92 and 1.5 Å resolution). HR RNA folds into a triplex structure composed of four RNA chains. ANP77 interacted with two neighboring single-stranded cytosines to form pseudo-canonical base pairs by adopting sandwich-like conformation and adjusting the position of its naphthyridine units to the helical twist of the RNA. In the unliganded structure, the cytosines formed a peculiar triplex i-motif, assembled by trans C•C+ pair and a third cytosine located at the Hoogsteen edge of the C•C+ pair. These results extend our knowledge of the structural polymorphisms of HR and can be used for rational design of small molecules targeting disease-related RNAs.}, } @article {pmid38738213, year = {2023}, author = {Fan, C and Hahn, N and Kamdar, F and Avansino, D and Wilson, GH and Hochberg, L and Shenoy, KV and Henderson, JM and Willett, FR}, title = {Plug-and-Play Stability for Intracortical Brain-Computer Interfaces: A One-Year Demonstration of Seamless Brain-to-Text Communication.}, journal = {Advances in neural information processing systems}, volume = {36}, number = {}, pages = {42258-42270}, pmid = {38738213}, issn = {1049-5258}, support = {R01 DC014034/DC/NIDCD NIH HHS/United States ; R01 EB028171/EB/NIBIB NIH HHS/United States ; U01 DC017844/DC/NIDCD NIH HHS/United States ; }, abstract = {Intracortical brain-computer interfaces (iBCIs) have shown promise for restoring rapid communication to people with neurological disorders such as amyotrophic lateral sclerosis (ALS). However, to maintain high performance over time, iBCIs typically need frequent recalibration to combat changes in the neural recordings that accrue over days. This requires iBCI users to stop using the iBCI and engage in supervised data collection, making the iBCI system hard to use. In this paper, we propose a method that enables self-recalibration of communication iBCIs without interrupting the user. Our method leverages large language models (LMs) to automatically correct errors in iBCI outputs. The self-recalibration process uses these corrected outputs ("pseudo-labels") to continually update the iBCI decoder online. Over a period of more than one year (403 days), we evaluated our Continual Online Recalibration with Pseudo-labels (CORP) framework with one clinical trial participant. CORP achieved a stable decoding accuracy of 93.84% in an online handwriting iBCI task, significantly outperforming other baseline methods. Notably, this is the longest-running iBCI stability demonstration involving a human participant. Our results provide the first evidence for long-term stabilization of a plug-and-play, high-performance communication iBCI, addressing a major barrier for the clinical translation of iBCIs.}, } @article {pmid38738022, year = {2024}, author = {De Jesus-Morales, K and De Jesús-Rojas, W and Ramos-Benitez, MJ}, title = {Neutrophil-to-Lymphocyte Ratio Dynamics From Pre-diagnosis to End-Stage Amyotrophic Lateral Sclerosis (ALS): A Case Study on Association With Progression and Clinical Events.}, journal = {Cureus}, volume = {16}, number = {4}, pages = {e58109}, pmid = {38738022}, issn = {2168-8184}, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative condition characterized by the progressive degeneration of motor neurons, resulting in muscle weakness and paralysis. The neutrophil-to-lymphocyte ratio (NLR) has emerged as a potential marker for monitoring disease severity and progression in ALS, yet longitudinal analyses of NLR are limited. Our study conducts an in-depth examination of NLR dynamics from before diagnosis through the disease's progression to its end stage. We analyze the case of a 56-year-old Puerto Rican male with ALS, tracking his NLR over 13 years - six years before and seven years after his diagnosis - alongside assessments of clinical symptoms and lung function. Our findings indicate that NLR values were initially normal but significantly increased with the onset of symptoms. NLR remained elevated above the normal range, with a notable exception during a period of edaravone therapy when levels normalized. The study demonstrates a clear elevation in NLR associated with ALS progression and critical clinical events, such as symptom onset, diagnosis, and the initiation of respiratory support. This research is, to our knowledge, the first to provide a detailed characterization of NLR changes from the pre-diagnostic phase to end-stage ALS, showing its correlation with clinical deterioration, decreased pulmonary function, and key clinical events. Our results contribute to the body of evidence on NLR's role in ALS while enhancing our understanding of ALS's natural progression.}, } @article {pmid38735361, year = {2024}, author = {D'Agostino, F and Agrò, FE and Petrosino, P and Ferri, C and Ristagno, G}, title = {Are instructors correctly gauging ventilation competence acquired by course attendees?.}, journal = {Resuscitation}, volume = {200}, number = {}, pages = {110240}, doi = {10.1016/j.resuscitation.2024.110240}, pmid = {38735361}, issn = {1873-1570}, mesh = {Humans ; *Clinical Competence/standards ; *Cardiopulmonary Resuscitation/education/standards/methods ; Respiration, Artificial/standards/methods/instrumentation ; Educational Measurement/methods ; Male ; Female ; Manikins ; Tidal Volume/physiology ; }, abstract = {Achievement of adequate ventilation skills during training courses is mainly based on instructors' perception of attendees' capability to ventilate with correct rate and chest compression:ventilation ratio, while leading to chest raising, as evidence of adequate tidal volume. Accuracy in evaluating ventilation competence was assessed in 20 ACLS provider course attendees, by comparing course instructors' evaluation with measures from a ventilation feedback device. According to course instructors, all candidates acquired adequate ventilation competence. However, data from the feedback device indicated a ventilation not aligned with current guidelines, with higher tidal volume and lower rate (p < 0.01). Deploying quality ventilation during CPR is a skill whose acquisition starts with effective training. Therefore, course instructors' capability to accurately evaluate attendees' ventilation maneuvers is crucial.}, } @article {pmid38735299, year = {2024}, author = {Gould, RL and McDermott, CJ and Thompson, BJ and Rawlinson, CV and Bursnall, M and Bradburn, M and Kumar, P and Turton, EJ and White, DA and Serfaty, MA and Graham, CD and McCracken, LM and Goldstein, LH and Al-Chalabi, A and Orrell, RW and Williams, T and Noad, R and Baker, I and Faull, C and Lambert, T and Chhetri, SK and Ealing, J and Hanratty, A and Radunovic, A and Gunawardana, N and Meadows, G and Gorrie, GH and Young, T and Lawrence, V and Cooper, C and Shaw, PJ and Howard, RJ and , }, title = {Acceptance and Commitment Therapy plus usual care for improving quality of life in people with motor neuron disease (COMMEND): a multicentre, parallel, randomised controlled trial in the UK.}, journal = {Lancet (London, England)}, volume = {403}, number = {10442}, pages = {2381-2394}, doi = {10.1016/S0140-6736(24)00533-6}, pmid = {38735299}, issn = {1474-547X}, support = {NIHR202421//NIHR/ ; }, mesh = {Humans ; *Quality of Life ; *Acceptance and Commitment Therapy/methods ; Male ; Female ; Middle Aged ; *Motor Neuron Disease/therapy/psychology ; United Kingdom ; Aged ; Treatment Outcome ; }, abstract = {BACKGROUND: Motor neuron disease is a progressive, fatal neurodegenerative disease for which there is no cure. Acceptance and Commitment Therapy (ACT) is a psychological therapy incorporating acceptance, mindfulness, and behaviour change techniques. We aimed to evaluate the effectiveness of ACT plus usual care, compared with usual care alone, for improving quality of life in people with motor neuron disease.

METHODS: We conducted a parallel, multicentre, two-arm randomised controlled trial in 16 UK motor neuron disease care centres or clinics. Eligible participants were aged 18 years or older with a diagnosis of definite or laboratory-supported probable, clinically probable, or possible familial or sporadic amyotrophic lateral sclerosis; progressive muscular atrophy; or primary lateral sclerosis; which met the World Federation of Neurology's El Escorial diagnostic criteria. Participants were randomly assigned (1:1) to receive up to eight sessions of ACT adapted for people with motor neuron disease plus usual care or usual care alone by a web-based system, stratified by site. Participants were followed up at 6 months and 9 months post-randomisation. Outcome assessors and trial statisticians were masked to treatment allocation. The primary outcome was quality of life using the McGill Quality of Life Questionnaire-Revised (MQOL-R) at 6 months post-randomisation. Primary analyses were multi-level modelling and modified intention to treat among participants with available data. This trial was pre-registered with the ISRCTN Registry (ISRCTN12655391).

FINDINGS: Between Sept 18, 2019, and Aug 31, 2022, 435 people with motor neuron disease were approached for the study, of whom 206 (47%) were assessed for eligibility, and 191 were recruited. 97 (51%) participants were randomly assigned to ACT plus usual care and 94 (49%) were assigned to usual care alone. 80 (42%) of 191 participants were female and 111 (58%) were male, and the mean age was 63·1 years (SD 11·0). 155 (81%) participants had primary outcome data at 6 months post-randomisation. After controlling for baseline scores, age, sex, and therapist clustering, ACT plus usual care was superior to usual care alone for quality of life at 6 months (adjusted mean difference on the MQOL-R of 0·66 [95% CI 0·22-1·10]; d=0·46 [0·16-0·77]; p=0·0031). Moderate effect sizes were clinically meaningful. 75 adverse events were reported, 38 of which were serious, but no adverse events were deemed to be associated with the intervention.

INTERPRETATION: ACT plus usual care is clinically effective for maintaining or improving quality of life in people with motor neuron disease. As further evidence emerges confirming these findings, health-care providers should consider how access to ACT, adapted for the specific needs of people with motor neuron disease, could be provided within motor neuron disease clinical services.

FUNDING: National Institute for Health and Care Research Health Technology Assessment and Motor Neurone Disease Association.}, } @article {pmid38735139, year = {2024}, author = {Im, G and Choi, D}, title = {Molecular and physiological characterization of AIP1, encoding the acetolactate synthase regulatory subunit in rice.}, journal = {Biochemical and biophysical research communications}, volume = {718}, number = {}, pages = {150087}, doi = {10.1016/j.bbrc.2024.150087}, pmid = {38735139}, issn = {1090-2104}, mesh = {*Oryza/genetics/metabolism/enzymology ; *Acetolactate Synthase/genetics/metabolism ; *Plant Proteins/genetics/metabolism ; *Gene Expression Regulation, Plant ; Plants, Genetically Modified ; Stress, Physiological/genetics ; Amino Acids, Branched-Chain/metabolism ; Oxygen/metabolism ; Protein Subunits/metabolism/genetics ; }, abstract = {Flooding deprives plants of oxygen and thereby causes severe stress by interfering with energy production, leading to growth retardation. Enzymes and metabolites may help protect plants from waterlogging and hypoxic environmental conditions. Acetolactate synthase (ALS) is a key enzyme in the biosynthesis of branched-chain amino acids (BCAAs), providing the building blocks for proteins and various secondary metabolites. Additionally, under energy-poor conditions, free BCAAs can be used as an alternative energy source by mitochondria through a catabolic enzyme chain reaction. In this study, we characterized ALS-INTERACTING PROTEIN 1 (OsAIP1), which encodes the regulatory subunit of ALS in rice (Oryza sativa). This gene was expressed in all parts of the rice plant, and its expression level was significantly higher in submerged and low-oxygen environments. Rice transformants overexpressing OsAIP1 showed a higher survival rate under hypoxic stress than did non-transgenic control plants under the same conditions. The OsAIP1-overexpressing plants accumulated increased levels of BCAAs, demonstrating that OsAIP1 is an important factor in the hypoxia resistance mechanism. These results suggest that ALS proteins are part of a defense mechanism that improves the tolerance of plants to low-oxygen environments.}, } @article {pmid38734896, year = {2024}, author = {Sun, S and Shen, Y and Zhang, X and Ding, N and Xu, Z and Zhang, Q and Li, L}, title = {The MuSK agonist antibody protects the neuromuscular junction and extends the lifespan in C9orf72-ALS mice.}, journal = {Molecular therapy : the journal of the American Society of Gene Therapy}, volume = {32}, number = {7}, pages = {2176-2189}, pmid = {38734896}, issn = {1525-0024}, mesh = {Animals ; *Neuromuscular Junction/metabolism/drug effects ; Mice ; *Amyotrophic Lateral Sclerosis/genetics/metabolism/drug therapy ; *C9orf72 Protein/genetics/metabolism ; Humans ; *Disease Models, Animal ; *Receptor Protein-Tyrosine Kinases/metabolism/genetics ; Longevity/drug effects ; Motor Neurons/metabolism/drug effects ; Agrin/metabolism/genetics ; Mice, Transgenic ; Antibodies/pharmacology ; Receptors, Cholinergic/metabolism/genetics ; LDL-Receptor Related Proteins/metabolism/genetics ; }, abstract = {The disassembly of the neuromuscular junction (NMJ) is an early event in amyotrophic lateral sclerosis (ALS), ultimately leading to motor dysfunction and lethal respiratory paralysis. The hexanucleotide GGGGCC repeat expansion in the C9orf72 gene is the most common genetic mutation, and the dipeptide repeat (DPR) proteins have been shown to cause neurodegeneration. While no drugs can treat ALS patients efficiently, new treatment strategies are urgently needed. Here, we report that a MuSK agonist antibody alleviates poly-PR-induced NMJ deficits in C9orf72-ALS mice. The HB9-PR[F/F] mice, which express poly-PR proteins in motor neurons, exhibited impaired motor behavior and NMJ deficits. Mechanistically, poly-PR proteins interacted with Agrin to disrupt the interaction between Agrin and Lrp4, leading to attenuated activation of MuSK. Treatment with a MuSK agonist antibody rescued NMJ deficits, and extended the lifespan of C9orf72-ALS mice. Moreover, impaired NMJ transmission was observed in C9orf72-ALS patients. These findings identify the mechanism by which poly-PR proteins attenuate MuSK activation and NMJ transmission, highlighting the potential of promoting MuSK activation with an agonist antibody as a therapeutic strategy to protect NMJ function and prolong the lifespan of ALS patients.}, } @article {pmid38734122, year = {2024}, author = {Panchalingam, S and Kasivelu, G}, title = {Exploring the impact of circular RNA on ALS progression: A systematic review.}, journal = {Brain research}, volume = {1838}, number = {}, pages = {148990}, doi = {10.1016/j.brainres.2024.148990}, pmid = {38734122}, issn = {1872-6240}, mesh = {*Amyotrophic Lateral Sclerosis/genetics/metabolism ; *RNA, Circular/metabolism/genetics ; Humans ; *Disease Progression ; Animals ; Motor Neurons/metabolism ; }, abstract = {Amyotrophic lateral sclerosis is a neurodegenerative disease that damages motor neurons and causes gradual muscular weakening and paralysis. Although studies have linked a number of genetic and environmental factors to ALS, the specific causes and mechanisms of the disease are still unclear. The pivotal role of circular RNA in the pathogenesis of ALS is a newly emerging area of research. The term "circular RNA" describes a particular class of RNA molecule that, in contrast to most RNA molecules, has a closed-loop structure. According to recent research, circular RNA might be essential for the development and progression of ALS. It has been discovered that these circular RNAs support important cellular functions related to ALS, including protein turnover, mitochondrial function, RNA processing, and cellular transport. Gaining knowledge about the precise roles and processes of circular RNA in the development of ALS could assist in understanding the pathophysiology of the disease and possibly pave the way for the development of targeted therapies. However, the understanding of circular RNA in ALS is still limited, and more research is needed to fully elucidate its role. In order to gain a comprehensive understanding of the role of circRNAs in ALS, it is imperative to delve into the various mechanisms through which circRNAs may contribute to the development and progression of the disease. Examining the current status of circRNA research in ALS and offering insights into their potential as therapeutic targets and diagnostic markers are the primary objectives of this review.}, } @article {pmid38733435, year = {2024}, author = {Liu, S and Hong, Y and Wang, BR and Wei, ZQ and Zhao, HD and Jiang, T and Zhang, YD and Shi, JQ}, title = {The presence and clinical significance of autoantibodies in amyotrophic lateral sclerosis: a narrative review.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {45}, number = {9}, pages = {4133-4149}, pmid = {38733435}, issn = {1590-3478}, mesh = {*Amyotrophic Lateral Sclerosis/immunology/blood ; Humans ; *Autoantibodies/immunology/blood ; Clinical Relevance ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a debilitating and rapidly fatal neurodegenerative disease, which is characterized by the selective loss of the upper and lower motor neurons. The pathogenesis of ALS remains to be elucidated and has been connected to genetic, environmental and immune conditions. Evidence from clinical and experimental studies has suggested that the immune system played an important role in ALS pathophysiology. Autoantibodies are essential components of the immune system. Several autoantibodies directed at antigens associated with ALS pathogenesis have been identified in the serum and/or cerebrospinal fluid of ALS patients. The aim of this review is to summarize the presence and clinical significance of autoantibodies in ALS.}, } @article {pmid38733354, year = {2024}, author = {Emile, R and Krisjanous, J and Banga, M and Kadirov, D}, title = {Healthcare access for pregnant women in a rural developing country context: Formal and informal institutional challenges.}, journal = {Health marketing quarterly}, volume = {41}, number = {3}, pages = {294-312}, doi = {10.1080/07359683.2024.2347047}, pmid = {38733354}, issn = {1545-0864}, mesh = {Humans ; Female ; *Health Services Accessibility ; Pregnancy ; *Rural Population ; *Developing Countries ; Adult ; Pregnant People/psychology ; }, abstract = {This study examines healthcare access for pregnant women in a rural developing country context. Drawing upon institutional theory and Levesque et al's model of access, the study finds pregnant women face challenges both of a formal and informal nature in accessing healthcare. The findings suggest the need for integrated and collaborative workings across formal and informal institutional networks. Theoretically, the study makes two contributions. First, it adds value to institutional theory by incorporating a dimension of access. Second, it builds upon Levesque et al.'s healthcare access framework by highlighting the role and significance of a third dimension-that is informal institutions, in addition to the current two-formal institutions and individual factors.}, } @article {pmid38732386, year = {2024}, author = {Zhang, Y and Zhao, A and Mu, L and Teng, X and Ma, Y and Li, R and Lei, K and Ji, L and Wang, X and Li, P}, title = {First Clarification of the Involvement of Glycosyltransferase MdUGT73CG22 in the Detoxification Metabolism of Nicosulfuron in Apple.}, journal = {Plants (Basel, Switzerland)}, volume = {13}, number = {9}, pages = {}, pmid = {38732386}, issn = {2223-7747}, support = {No. ZR202102180037//Shandong Provincial Natural Science Foundation of China/ ; No. LCUGYTD2022-04//Guangyue Young Scholar Innovation Team of Liaocheng University/ ; }, abstract = {Nicosulfuron, an acetolactate synthase (ALS) inhibitor herbicide, is a broad-spectrum and highly effective post-emergence herbicide. Glycosyltransferases (GTs) are widely found in organisms and transfer sugar molecules from donors to acceptors to form glycosides or sugar esters, thereby altering the physicochemical properties of the acceptor molecule, such as participating in detoxification. In this study, nine glycosyltransferases in group D of the apple glycosyltransferase family I were predicted to possibly be involved in the detoxification metabolism of ALS-inhibiting herbicides based on gene chip data published online. In order to confirm this, we analysed whether the expression of the nine glycosyltransferase genes in group D was induced by the previously reported ALS-inhibiting herbicides by real-time PCR (polymerase chain reaction). It was found that the ALS-inhibiting herbicide nicosulfuron significantly increased the expression of the MdUGT73CG22 gene in group D. Further investigation of the mechanism of action revealed that the apple glycosyltransferase MdUGT73CG22 glycosylated and modified nicosulfuron both in vivo and ex vivo to form nicosulfuron glycosides, which were involved in detoxification metabolism. In conclusion, a new glycosyltransferase, MdUGT73CG22, was identified for the first time in this study, which can glycosylate modifications of the ALS-inhibiting herbicide nicosulfuron and may be involved in the detoxification process in plants, which can help to further improve the knowledge of the non-targeted mechanism of herbicides.}, } @article {pmid38732027, year = {2024}, author = {Cantara, S and Simoncelli, G and Ricci, C}, title = {Antisense Oligonucleotides (ASOs) in Motor Neuron Diseases: A Road to Cure in Light and Shade.}, journal = {International journal of molecular sciences}, volume = {25}, number = {9}, pages = {}, pmid = {38732027}, issn = {1422-0067}, mesh = {Humans ; *Oligonucleotides, Antisense/therapeutic use ; *Motor Neuron Disease/genetics/therapy ; Animals ; Muscular Atrophy, Spinal/therapy/genetics ; Amyotrophic Lateral Sclerosis/genetics/therapy ; }, abstract = {Antisense oligonucleotides (ASOs) are short oligodeoxynucleotides designed to bind to specific regions of target mRNA. ASOs can modulate pre-mRNA splicing, increase levels of functional proteins, and decrease levels of toxic proteins. ASOs are being developed for the treatment of motor neuron diseases (MNDs), including spinal muscular atrophy (SMA), amyotrophic lateral sclerosis (ALS) and spinal and bulbar muscular atrophy (SBMA). The biggest success has been the ASO known as nusinersen, the first effective therapy for SMA, able to improve symptoms and slow disease progression. Another success is tofersen, an ASO designed to treat ALS patients with SOD1 gene mutations. Both ASOs have been approved by the FDA and EMA. On the other hand, ASO treatment in ALS patients with the C9orf72 gene mutation did not show any improvement in disease progression. The aim of this review is to provide an up-to-date overview of ASO research in MNDs, from preclinical studies to clinical trials and, where available, regulatory approval. We highlight the successes and failures, underline the strengths and limitations of the current ASO research, and suggest possible approaches that could lead to more effective treatments.}, } @article {pmid38731036, year = {2024}, author = {Ueha, R and Miura, C and Matsumoto, N and Sato, T and Goto, T and Kondo, K}, title = {Vocal Fold Motion Impairment in Neurodegenerative Diseases.}, journal = {Journal of clinical medicine}, volume = {13}, number = {9}, pages = {}, pmid = {38731036}, issn = {2077-0383}, abstract = {Vocal fold motion impairment (VFMI) is the inappropriate movement of the vocal folds during respiration, leading to vocal fold adduction and/or abduction problems and causing respiratory and vocal impairments. Neurodegenerative diseases (NDDs) are a wide range of disorders characterized by progressive loss of neurons and deposition of altered proteins in the brain and peripheral organs. VFMI may be unrecognized in patients with NDDs. VFMI in NDDs is caused by the following: laryngeal muscle weakness due to muscular atrophy, caused by brainstem and motor neuron degeneration in amyotrophic lateral sclerosis; hyperactivity of laryngeal adductors in Parkinson's disease; and varying degrees of laryngeal adductor hypertonia and abductor paralysis in multiple system atrophy. Management of VFMI depends on whether there is a presence of glottic insufficiency or insufficient glottic opening with/without severe dysphagia. VFMI treatment options for glottic insufficiency range from surgical interventions, including injection laryngoplasty and medialization thyroplasty, to behavioral therapies; for insufficient glottic opening, various options are available based on the severity and underlying cause of the condition, including continuous positive airway pressure therapy, botulinum toxin injection, tracheostomy, vocal fold surgery, or a combination of interventions. In this review, we outline the mechanisms, clinical features, and management of VFMI in NDDs and provide a guide for physicians who may encounter these clinical features in their patients. NDDs are always progressive; hence, timely evaluation, proper diagnosis, and appropriate management of the patient will greatly affect their vocal, respiratory, and swallowing functions as well as their quality of life.}, } @article {pmid38728654, year = {2024}, author = {McFarlane, R and Heverin, M and Walsh, C and Hardiman, O}, title = {Irish Amyotrophic Lateral Sclerosis Incidence: Age, Period, and Cohort Effects Using a Partial Least Squares Regression Model.}, journal = {Neurology}, volume = {102}, number = {11}, pages = {e209391}, doi = {10.1212/WNL.0000000000209391}, pmid = {38728654}, issn = {1526-632X}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/epidemiology ; Ireland/epidemiology ; Incidence ; Aged ; Middle Aged ; Male ; Female ; Adult ; Least-Squares Analysis ; Aged, 80 and over ; Registries ; Age Factors ; Cohort Effect ; Cohort Studies ; }, abstract = {BACKGROUND AND OBJECTIVES: To investigate the underlying reasons for variability in the incidence rate of amyotrophic lateral sclerosis (ALS) within the Irish population between the years 1996 and 2021.

METHODS: The Irish ALS register was used to calculate the incidence and to subsequently extract age at diagnosis (age), year of diagnosis (period), and date of birth (cohort) for all incident patients within the study period (n = 2,771). An age-period-cohort (APC) model using partial least squares regression was constructed to examine each component separately and their respective contribution to the incidence while minimizing the well-known identifiability problem of APC effects. A dummy regression model consisting of 5 periods, 19 cohorts, and 16 age groups was used to examine nonlinear relationships within the data over time. The CIs for each of these were estimated using the jackknife method.

RESULTS: The nonlinear model achieved R[2] of 99.43% with 2-component extraction. Age variation was evident with those in the ages 65-79 years contributing significantly to the incidence (βmax = 0.0746, SE = 0.000410, CI 0.00665-0.00826). However, those aged 25-60 years contributed significantly less (βmin = -0.00393, SE = 0.000291, CI -0.00454 to -0.00340). Each successive period showed an increase in the regression model coefficient suggesting an increasing incidence over time, independent of the other factors examined-an increase of β from -0.00489 (SE = 0.000264, CI -0.00541 to -0.00437) to 0.00973 (SE = 0.000418, CI 0.0105-0.00891). A cohort effect was demonstrated showing that the contribution of those born between 1927 and 1951 contributed to a significantly greater degree than the other birth cohorts (βmax = 0.00577, SE = 0.000432, CI 0.00493-0.00662).

DISCUSSION: Using the Irish population-based ALS Register, robust age, period, and cohort effects can be identified. The age effect may be accounted for by demographic shifts within the population. Changes in disease categorization, competing risks of death, and improved surveillance may account for period effects. The cohort effect may reflect lifestyle and environmental factors associated with the challenging economic circumstances in Ireland between 1927 and 1951. Age-period-cohort studies can help to account for changes in disease incidence and prevalence, providing additional insights into likely demographic and environmental factors that influence population-based disease risk.}, } @article {pmid38727285, year = {2024}, author = {Gao, Y and Lu, Y and Liang, X and Zhao, M and Yu, X and Fu, H and Yang, W}, title = {CD4[+] T-Cell Senescence in Neurodegenerative Disease: Pathogenesis and Potential Therapeutic Targets.}, journal = {Cells}, volume = {13}, number = {9}, pages = {}, pmid = {38727285}, issn = {2073-4409}, support = {20230505039ZP//Jilin Province Science and Technology Department/ ; }, mesh = {Animals ; Humans ; Aging/immunology/pathology ; *CD4-Positive T-Lymphocytes/immunology ; *Neurodegenerative Diseases/immunology/pathology/therapy ; *T-Cell Senescence ; }, abstract = {With the increasing proportion of the aging population, neurodegenerative diseases have become one of the major health issues in society. Neurodegenerative diseases (NDs), including multiple sclerosis (MS), Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS), are characterized by progressive neurodegeneration associated with aging, leading to a gradual decline in cognitive, emotional, and motor functions in patients. The process of aging is a normal physiological process in human life and is accompanied by the aging of the immune system, which is known as immunosenescence. T-cells are an important part of the immune system, and their senescence is the main feature of immunosenescence. The appearance of senescent T-cells has been shown to potentially lead to chronic inflammation and tissue damage, with some studies indicating a direct link between T-cell senescence, inflammation, and neuronal damage. The role of these subsets with different functions in NDs is still under debate. A growing body of evidence suggests that in people with a ND, there is a prevalence of CD4[+] T-cell subsets exhibiting characteristics that are linked to senescence. This underscores the significance of CD4[+] T-cells in NDs. In this review, we summarize the classification and function of CD4[+] T-cell subpopulations, the characteristics of CD4[+] T-cell senescence, the potential roles of these cells in animal models and human studies of NDs, and therapeutic strategies targeting CD4[+] T-cell senescence.}, } @article {pmid38726604, year = {2024}, author = {López Gómez, JJ and Díaz Marín, C and Castillo-García, T and Larrad-Sainz, A and Gastaldo-Simeón, R and Juarros-Martínez, S and Leunda-Eizmendi, L and Civera Andrés, M and Matía Martín, P}, title = {[Medical nutrition therapy in amyotrophic lateral sclerosis - Do we act or react? A case report and multidisciplinary review].}, journal = {Nutricion hospitalaria}, volume = {41}, number = {3}, pages = {712-723}, doi = {10.20960/nh.05189}, pmid = {38726604}, issn = {1699-5198}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy/complications ; *Malnutrition/etiology/therapy ; *Nutrition Therapy/methods ; Nutritional Status ; }, abstract = {Background: amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with a progressive course. The current prevalence is between 3 and 6 cases/100,000. Malnutrition is closely related to patient prognosis in ALS. The implications of this conditions have been that we should recommend patient care in a multidisciplinary unit. Case report: the case presented shows the evolution of a patient with ALS. The patient was referred to different clinical departments after neurological evaluation and her nutritional, functional and respiratory status were assessed. There was no nutritional deterioration at diagnosis; however, intake was below energy-protein requirements. The clinical evolution of the patient showed a decrease in muscle mass with preservation of weight and fat mass. "Aggressive" measures to control nutritional status such as gastrostomy were rejected in the initial stages of the disease, but had to be carried out after development of dysphagia and associated malnutrition. This situation of progressive morphofunctional deterioration and the development of disease-related complications made essential the participation of different health services and professionals in its control. Dicussion: the management of ALS in a multidisciplinary manner allows to improve the course of the disease and the quality of life of both the patients and their families. Patient follow-up is based on the adjustment and management of complications. The basis of the relationship with these patients includes maintaining an adequate communication with them and their families, and ensuring joint decision-making about their condition.}, } @article {pmid38726482, year = {2024}, author = {Henden, L and Fearnley, LG and Southwood, D and Smith, A and Rowe, DB and Kiernan, MC and Pamphlett, R and Bahlo, M and Blair, IP and Williams, KL}, title = {Short tandem repeat expansions in LRP12 are absent in cohorts of familial and sporadic amyotrophic lateral sclerosis patients of European ancestry.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {25}, number = {5-6}, pages = {644-647}, doi = {10.1080/21678421.2024.2348636}, pmid = {38726482}, issn = {2167-9223}, mesh = {Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; *Amyotrophic Lateral Sclerosis/genetics ; Cohort Studies ; Trinucleotide Repeat Expansion ; *White People/genetics ; *Low Density Lipoprotein Receptor-Related Protein-1/genetics ; }, abstract = {In patients of Asian ancestry, a heterozygous CGG repeat expansion of >100 units in LRP12 is the cause of oculopharyngodistal myopathy type 1 (OPDM1). Repeat lengths of between 61 and 100 units have been associated with rare amyotrophic lateral sclerosis (ALS) cases of Asian ancestry, although with unusually long disease duration and without significant upper motor neuron involvement. This study sought to determine whether LRP12 CGG repeat expansions were also present in ALS patients of European ancestry. Whole-genome sequencing data from 608 sporadic ALS patients, 35 familial ALS probands, and 4703 neurologically normal controls were screened for LRP12 CGG expansions using ExpansionHunter v4. All individuals had LRP12 CGG repeat lengths within the normal range of 3-25 units. To date, LRP12 CGG repeat expansions have not been reported in ALS patients of European ancestry and may be limited to rare ALS patients of Asian ancestry and atypical clinical presentations.}, } @article {pmid38725125, year = {2024}, author = {Kim, D and Kim, S and Seok, JM and Shin, KJ and Oh, E and Jeon, MY and Park, J and Chang, HJ and Youn, J and Oh, J and Sohn, E and Park, J and Cho, JW and Kim, BJ}, title = {Establishment of a registry of clinical data and bioresources for rare nervous system diseases.}, journal = {Osong public health and research perspectives}, volume = {15}, number = {2}, pages = {174-181}, pmid = {38725125}, issn = {2210-9099}, support = {2023ER050600//National Institute of Health research/ ; }, abstract = {Rare diseases are predominantly genetic or inherited, and patients with these conditions frequently exhibit neurological symptoms. Diagnosing and treating many rare diseases is a complex challenge, and their low prevalence complicates the performance of research, which in turn hinders the advancement of therapeutic options. One strategy to address this issue is the creation of national or international registries for rare diseases, which can help researchers monitor and investigate their natural progression. In the Republic of Korea, we established a registry across 5 centers that focuses on 3 rare diseases, all of which are characterized by gait disturbances resulting from motor system dysfunction. The registry will collect clinical information and human bioresources from patients with amyotrophic lateral sclerosis, spinocerebellar ataxia, and hereditary spastic paraplegia. These resources will be stored at ICreaT and the National Biobank of Korea. Once the registry is complete, the data will be made publicly available for further research. Through this registry, our research team is dedicated to identifying genetic variants that are specific to Korean patients, uncovering biomarkers that show a strong correlation with clinical symptoms, and leveraging this information for early diagnosis and the development of treatments.}, } @article {pmid38724513, year = {2024}, author = {Zhou, T and Solis, NV and Marshall, M and Yao, Q and Garleb, R and Yang, M and Pearlman, E and Filler, SG and Liu, H}, title = {Hyphal Als proteins act as CR3 ligands to promote immune responses against Candida albicans.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {3926}, pmid = {38724513}, issn = {2041-1723}, support = {R01 GM117111/GM/NIGMS NIH HHS/United States ; R01 EY018612/EY/NEI NIH HHS/United States ; }, mesh = {Animals ; Mice ; beta-Glucans/metabolism/immunology ; Candida albicans/immunology ; *Candidiasis/immunology/microbiology ; CD11b Antigen/metabolism/immunology ; *CD18 Antigens/metabolism ; Dendritic Cells/immunology/metabolism ; *Fungal Proteins/metabolism/immunology ; *Lectins, C-Type/metabolism/immunology ; *Macrophages/immunology/metabolism ; Signal Transduction ; }, abstract = {Patients with decreased levels of CD18 (β2 integrins) suffer from life-threatening bacterial and fungal infections. CD11b, the α subunit of integrin CR3 (CD11b/CD18, αMβ2), is essential for mice to fight against systemic Candida albicans infections. Live elongating C. albicans activates CR3 in immune cells. However, the hyphal ligands that activate CR3 are not well defined. Here, we discovered that the C. albicans Als family proteins are recognized by the I domain of CD11b in macrophages. This recognition synergizes with the β-glucan-bound lectin-like domain to activate CR3, thereby promoting Syk signaling and inflammasome activation. Dectin-2 activation serves as the "outside-in signaling" for CR3 activation at the entry site of incompletely sealed phagosomes, where a thick cuff of F-actin forms to strengthen the local interaction. In vitro, CD18 partially contributes to IL-1β release from dendritic cells induced by purified hyphal Als3. In vivo, Als3 is vital for C. albicans clearance in mouse kidneys. These findings uncover a novel family of ligands for the CR3 I domain that promotes fungal clearance.}, } @article {pmid38723941, year = {2024}, author = {Doeleman, LC and Boomars, R and Radstok, A and Schober, P and Dellaert, Q and Hollmann, MW and Koster, RW and van Schuppen, H}, title = {Ventilation during cardiopulmonary resuscitation with mechanical chest compressions: How often are two insufflations being given during the 3-second ventilation pauses?.}, journal = {Resuscitation}, volume = {199}, number = {}, pages = {110234}, doi = {10.1016/j.resuscitation.2024.110234}, pmid = {38723941}, issn = {1873-1570}, mesh = {Humans ; *Cardiopulmonary Resuscitation/methods ; *Out-of-Hospital Cardiac Arrest/therapy ; Male ; Female ; *Insufflation/methods ; Middle Aged ; Prospective Studies ; *Heart Massage/methods ; Aged ; Netherlands ; Time Factors ; Respiration, Artificial/methods ; Emergency Medical Services/methods ; Registries ; }, abstract = {BACKGROUND: Mechanical chest compression devices in 30:2 mode provide 3-second pauses to allow for two insufflations. We aimed to determine how often two insufflations are provided in these ventilation pauses, in order to assess if prehospital providers are able to ventilate out-of-hospital cardiac arrest (OHCA) patients successfully during mechanical chest compressions.

METHODS: Data from OHCA cases of the regional ambulance service of Utrecht, The Netherlands, were prospectively collected in the UTrecht studygroup for OPtimal registry of cardIAc arrest database (UTOPIA). Compression pauses and insufflations were visualized on thoracic impedance and waveform capnography signals recorded by manual defibrillators. Ventilation pauses were analyzed for number of insufflations, duration of the subintervals of the ventilation cycles, and ratio of successfully providing two insufflations over the course of the resuscitation. Generalized linear mixed effects models were used to accurately estimate proportions and means.

RESULTS: In 250 cases, 8473 ventilation pauses were identified, of which 4305 (51%) included two insufflations. When corrected for non-independence of the data across repeated measures within the same subjects with a mixed effects analysis, two insufflations were successfully provided in 45% of ventilation pauses (95% CI: 40-50%). In 19% (95% CI: 16-22%) none were given.

CONCLUSION: Providing two insufflations during pauses in mechanical chest compressions is mostly unsuccessful. We recommend developing strategies to improve giving insufflations when using mechanical chest compression devices. Increasing the pause duration might help to improve insufflation success.}, } @article {pmid38723906, year = {2024}, author = {Koike, Y}, title = {Molecular mechanisms linking loss of TDP-43 function to amyotrophic lateral sclerosis/frontotemporal dementia-related genes.}, journal = {Neuroscience research}, volume = {208}, number = {}, pages = {1-7}, doi = {10.1016/j.neures.2024.05.001}, pmid = {38723906}, issn = {1872-8111}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/metabolism ; *DNA-Binding Proteins/genetics/metabolism ; *Frontotemporal Dementia/genetics/metabolism ; Animals ; Polymorphism, Single Nucleotide ; Aging/genetics/metabolism ; }, abstract = {Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are characterized by nuclear depletion and cytoplasmic aggregation of TAR DNA-binding protein-43 (TDP-43). TDP-43 plays a key role in regulating the splicing of numerous genes, including TARDBP. This review aims to delineate two aspects of ALS/FTD pathogenesis associated with TDP-43 function. First, we described novel mechanistic insights into the splicing of UNC13A, a TDP-43 target gene. Single nucleotide polymorphisms (SNPs) in UNC13A are the most common risk factors for ALS/FTD. We found that TDP-43 represses "cryptic exon" inclusion during UNC13A RNA splicing. A risk-associated SNP in this exon results in increased RNA levels of UNC13A retaining the cryptic exon. Second, we described the perturbation of the TDP-43 autoregulatory mechanism caused by age-related DNA demethylation. Aging is a major risk factor for sporadic ALS/FTD. Typically, TDP-43 levels are regulated via alternative splicing of TARDBP mRNA. This review focused on that TARDBP methylation is altered by aging, thereby disrupting TDP-43 autoregulation. It was found that demethylation reduces the efficiency of alternative splicing and increases TARDBP mRNA levels. Moreover, we demonstrated that, with aging, this region is demethylated in the human motor cortex and is associated with the early onset of ALS.}, } @article {pmid38723752, year = {2024}, author = {Singh, K and Sethi, P and Datta, S and Chaudhary, JS and Kumar, S and Jain, D and Gupta, JK and Kumar, S and Guru, A and Panda, SP}, title = {Advances in gene therapy approaches targeting neuro-inflammation in neurodegenerative diseases.}, journal = {Ageing research reviews}, volume = {98}, number = {}, pages = {102321}, doi = {10.1016/j.arr.2024.102321}, pmid = {38723752}, issn = {1872-9649}, mesh = {Humans ; *Genetic Therapy/methods/trends ; *Neurodegenerative Diseases/therapy/genetics ; *Neuroinflammatory Diseases/therapy ; Animals ; }, abstract = {Over the last three decades, neurodegenerative diseases (NDs) have increased in frequency. About 15% of the world's population suffers from NDs in some capacity, which causes cognitive and physical impairment. Neurodegenerative diseases, including Amyotrophic Lateral Sclerosis, Parkinson's disease, Alzheimer's disease, and others represent a significant and growing global health challenge. Neuroinflammation is recognized to be related to all NDs, even though NDs are caused by a complex mix of genetic, environmental, and lifestyle factors. Numerous genes and pathways such as NFκB, p38 MAPK, Akt/mTOR, caspase, nitric oxide, and COX are involved in triggering brain immune cells like astrocytes and microglia to secrete inflammatory cytokines such as tumor necrosis factor-α, interleukin (IL)-1β, and IL-6. In AD, the binding of Aβ with CD36, TLR4, and TLR6 receptors results in activation of microglia which start to produce proinflammatory cytokines and chemokines. Consequently, the pro-inflammatory cytokines worsen and spread neuroinflammation, causing the deterioration of healthy neurons and the impairment of brain functions. Gene therapy has emerged as a promising therapeutic approach to modulate the inflammatory response in NDs, offering potential neuroprotective effects and disease-modifying benefits. This review article focuses on recent advances in gene therapy strategies targeting neuroinflammation pathways in NDs. We discussed the molecular pathways involved in neuroinflammation, highlighted key genes and proteins implicated in these processes, and reviewed the latest preclinical and clinical studies utilizing gene therapy to modulate neuroinflammatory responses. Additionally, this review addressed the prospects and challenges in translating gene therapy approaches into effective treatments for NDs.}, } @article {pmid38722513, year = {2024}, author = {Sultana, J and Ragagnin, AMG and Parakh, S and Saravanabavan, S and Soo, KY and Vidal, M and Jagaraj, CJ and Ding, K and Wu, S and Shadfar, S and Don, EK and Deva, A and Nicholson, G and Rowe, DB and Blair, I and Yang, S and Atkin, JD}, title = {C9orf72-Associated Dipeptide Repeat Expansions Perturb ER-Golgi Vesicular Trafficking, Inducing Golgi Fragmentation and ER Stress, in ALS/FTD.}, journal = {Molecular neurobiology}, volume = {61}, number = {12}, pages = {10318-10338}, pmid = {38722513}, issn = {1559-1182}, support = {10305133//National Health and Medical Research Council/ ; 1086887//National Health and Medical Research Council/ ; 1095215//National Health and Medical Research Council/ ; 1176913//National Health and Medical Research Council/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology ; *C9orf72 Protein/genetics/metabolism ; Humans ; *Frontotemporal Dementia/genetics/metabolism/pathology ; *Golgi Apparatus/metabolism ; *Endoplasmic Reticulum Stress/genetics ; *Endoplasmic Reticulum/metabolism ; *Dipeptides/metabolism ; *DNA Repeat Expansion/genetics ; Protein Transport ; }, abstract = {Hexanucleotide repeat expansions (HREs) in the chromosome 9 open reading frame 72 (C9orf72) gene are the most frequent genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Both are debilitating neurodegenerative conditions affecting either motor neurons (ALS) in the brain and spinal cord or neurons in the frontal and/or temporal cortical lobes (FTD). HREs undergo repeat-associated non-ATG (RAN) translation on both sense and anti-sense strands, generating five distinct dipeptide repeat proteins (DPRs), poly-GA, -GR, -GP, -PA and -PR. Perturbed proteostasis is well-recognised in ALS pathogenesis, including processes affecting the endoplasmic reticulum (ER) and Golgi compartments. However, these mechanisms have not been well characterised for C9orf72-mediated ALS/FTD. In this study we demonstrate that C9orf72 DPRs polyGA, polyGR and polyGP (× 40 repeats) disrupt secretory protein transport from the ER to the Golgi apparatus in neuronal cells. Consistent with this finding, these DPRs also induce fragmentation of the Golgi apparatus, activate ER stress, and inhibit the formation of the omegasome, the precursor of the autophagosome that originates from ER membranes. We also demonstrate Golgi fragmentation in cells undergoing RAN translation that express polyGP. Furthermore, dysregulated ER-Golgi transport was confirmed in C9orf72 patient dermal fibroblasts. Evidence of aberrant ER-derived vesicles in spinal cord motor neurons from C9orf72 ALS patients compared to controls was also obtained. These data thus confirm that ER proteostasis and ER-Golgi transport is perturbed in C9orf72-ALS in the absence of protein over-expression. Hence this study identifies novel molecular mechanisms associated with the ER and Golgi compartments induced by the C9orf72 HRE.}, } @article {pmid38721655, year = {2024}, author = {Christoforidou, E and Moody, L and Joilin, G and Simoes, FA and Gordon, D and Talbot, K and Hafezparast, M}, title = {An ALS-associated mutation dysregulates microglia-derived extracellular microRNAs in a sex-specific manner.}, journal = {Disease models & mechanisms}, volume = {17}, number = {5}, pages = {}, pmid = {38721655}, issn = {1754-8411}, support = {//University of Sussex/ ; Hafezparast/Apr21/880-791/MNDA_/Motor Neurone Disease Association/United Kingdom ; DOD/14/30-PF12794//My Name'5 Doddie Foundation/ ; }, mesh = {*Microglia/metabolism/pathology ; *Amyotrophic Lateral Sclerosis/genetics/pathology ; *MicroRNAs/genetics/metabolism ; Animals ; Female ; *Mice, Transgenic ; Male ; *Mutation/genetics ; *Sex Characteristics ; DNA-Binding Proteins/genetics/metabolism ; Mice ; Extracellular Space/metabolism ; Humans ; Lipopolysaccharides/pharmacology ; Gene Expression Regulation ; }, abstract = {Evidence suggests the presence of microglial activation and microRNA (miRNA) dysregulation in amyotrophic lateral sclerosis (ALS), the most common form of adult motor neuron disease. However, few studies have investigated whether the miRNA dysregulation originates from microglia. Furthermore, TDP-43 (encoded by TARDBP), involved in miRNA biogenesis, aggregates in tissues of ∼98% of ALS cases. Thus, this study aimed to determine whether expression of the ALS-linked TDP-43M337V mutation in a transgenic mouse model dysregulates microglia-derived miRNAs. RNA sequencing identified several dysregulated miRNAs released by transgenic microglia and a differential miRNA release by lipopolysaccharide-stimulated microglia, which was more pronounced in cells from female mice. We validated the downregulation of three candidate miRNAs, namely, miR-16-5p, miR-99a-5p and miR-191-5p, by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and identified their predicted targets, which primarily include genes involved in neuronal development and function. These results suggest that altered TDP-43 function leads to changes in the miRNA population released by microglia, which may in turn be a source of the miRNA dysregulation observed in the disease. This has important implications for the role of neuroinflammation in ALS pathology and could provide potential therapeutic targets.}, } @article {pmid38721118, year = {2024}, author = {Lu, L and Deng, Y and Xu, R}, title = {Current potential therapeutics of amyotrophic lateral sclerosis.}, journal = {Frontiers in neurology}, volume = {15}, number = {}, pages = {1402962}, pmid = {38721118}, issn = {1664-2295}, abstract = {Amyotrophic lateral sclerosis (ALS) is a debilitating motor neurological disorder for which there is still no cure. The disease seriously jeopardizes the health and lifespan of adult populations. The authors extensively retrieved the current literature about clinical and experimental ALS treatments. Based on them, this review primarily focused on summarizing the current potential clinical usage and trialing therapeutics of ALS. Currently, the clinical ALS treatments have focused primarily on relieving symptoms to improve the quality of life yet. There are a number of therapeutic approaches such as medicine, gene therapy, neuron protectants, combination therapy and stem cells. Among them, Stem cells including embryonic stem cells, mesenchymal stem cells, neural stem cells, and many other types of stem cells have been used in ALS treatment, and although the short-term efficacy is good, it is worth exploring whether this improved efficacy leads to prolonged patient survival. In addition, the supportive treatments also exert an important effect on improving the quality of life and prolong the survival of ALS patients in absence of effectively care for stopping or reversing the progression of ALS.}, } @article {pmid38720896, year = {2024}, author = {Zong, J and Yang, Y and Wang, H and Zhang, H and Yang, X and Yang, X}, title = {The two-directional prospective association between inflammatory bowel disease and neurodegenerative disorders: a systematic review and meta-analysis based on longitudinal studies.}, journal = {Frontiers in immunology}, volume = {15}, number = {}, pages = {1325908}, pmid = {38720896}, issn = {1664-3224}, mesh = {Humans ; *Inflammatory Bowel Diseases/complications ; *Neurodegenerative Diseases/epidemiology/etiology ; Longitudinal Studies ; Risk Factors ; Prospective Studies ; }, abstract = {OBJECTIVE: Previous studies reported possible connections between inflammatory bowel disease (IBD) and several neurodegenerative disorders. However, the comprehensive relationships between IBD and various neurodegenerative disorders were not summarized. We executed a meta-analysis of longitudinal studies to provide an estimate of the strength of the two-directional prospective association between IBD and neurodegenerative disorders.

METHODS: We accomplished a thorough bibliographic search of PubMed, Web of Science, Embase, PsycINFO, and Cochrane Library databases until June 2023 to locate relevant longitudinal studies. The extracted data were then analyzed via meta-analysis using either a fixed or random effects model.

RESULTS: The final analysis encompassed 27 studies. Individuals with IBD faced an increased risk of developing four neurodegenerative disorders than the general public, namely, Alzheimer's disease (hazard ratio[HR] = 1.35, 95% confidence interval [CI]: 1.03-1.77, P=0.031), dementia (HR =1.24, 95% CI: 1.13-1.36, P<0.001), multiple sclerosis (HR =2.07, 95% CI:1.42-3.02, P<0.001) and Parkinson's disease (HR =1.23, 95% CI:1.10-1.38, P<0.001). Two articles reported an increased incidence of amyotrophic lateral sclerosis or multiple system atrophy in IBD patients. Three studies investigated the prospective association between multiple sclerosis and IBD, revealing an elevated risk of the latter in patients with the former. (HR=1.87, 95% CI:1.66-2.10, P<0.001).

INTERPRETATION: These findings verified the two-directional relationship between the brain-gut axis, specifically demonstrating a heightened risk of various neurodegenerative diseases among IBD patients. It may be profitable to prepare screening strategies for IBD patients to find neurodegenerative diseases during the long-term course of treatment for IBD with a view to potential earlier diagnosis and treatment of neurodegenerative diseases, reducing public health and social burden.

PROSPERO (CRD42023437553).}, } @article {pmid38720484, year = {2024}, author = {Fernandes, JMA and Gondim, FAA}, title = {A homozygous p.Val120Leu (c.358G > C) SOD1 mutation led to slowly progressive amyotrophic lateral sclerosis in a Brazilian family.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {25}, number = {7-8}, pages = {788-790}, doi = {10.1080/21678421.2024.2346824}, pmid = {38720484}, issn = {2167-9223}, mesh = {Humans ; Male ; *Amyotrophic Lateral Sclerosis/genetics/diagnosis ; Adult ; *Superoxide Dismutase-1/genetics ; Brazil ; *Mutation/genetics ; *Disease Progression ; Pedigree ; Superoxide Dismutase/genetics ; Homozygote ; Female ; Middle Aged ; Valine/genetics ; Leucine/genetics ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease usually associated with severe weakness and death within 2-5 years. SOD1 mutations cause hereditary ALS in autosomal dominant and rarely in recessive pattern. We describe a new phenotype of slowly progressive fALS due to homozygous SOD1 mutations (c.358G > C, p.Val120Leu) in a Brazilian family. We reviewed the medical chart and interviewed the index patient and other relatives. A 41-year-old man developed weakness in his legs, leading to frequent falls, followed over the next few months with progressive arm fasciculations and muscle atrophy. The SOD1 enzymatic activity in erythrocytes was slightly decreased. A genetic test panel disclosed homozygous SOD1 mutations (c.358G > C, p.Val120Leu). His asymptomatic parents also carried one mutant allele and 2 brothers and a sister had died with ALS. We reported a new family with homozygous SOD1 mutation and slowly progressive ALS course. Further studies are necessary to confirm whether this mutation can also lead to disease in heterozygosis with incomplete penetrance.}, } @article {pmid38720470, year = {2024}, author = {Didcote, L and Al-Chalabi, A and Goldstein, LH}, title = {How the coronavirus pandemic affected the lives of people with ALS and their spouses in the UK from spouses' perspectives: a qualitative study.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {25}, number = {5-6}, pages = {625-633}, pmid = {38720470}, issn = {2167-9223}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/psychology/epidemiology ; *Spouses/psychology ; *COVID-19/psychology/epidemiology ; Male ; Female ; Middle Aged ; *Qualitative Research ; Aged ; United Kingdom/epidemiology ; SARS-CoV-2 ; Caregivers/psychology ; Adult ; Anxiety/psychology/epidemiology ; }, abstract = {OBJECTIVE: This study set out to investigate, using qualitative methodology, the experiences of spouses of people with Amyotrophic Lateral Sclerosis (ALS) during the coronavirus pandemic, with particular focus on spouse distress and cognitive and behavioral change in people with ALS (pwALS).

METHODS: Qualitative semi-structured interviews of nine spouses of pwALS living in England were conducted between 11/09/2020 and 20/04/2021, focusing on spouses' perspectives of how their lives and the lives of pwALS were affected by the pandemic and related lockdowns. Interviews were subject to thematic analysis.

RESULTS: Four superordinate themes were identified from the spouses' interviews: (i) pandemic behaviors, which encompassed accounts of cautious behavior, relaxation of cautious behavior, and other people's attitudes to shielding the person with ALS; (ii) changes to daily life caused by the pandemic and progression of ALS; (iii) distress in spouses, which included anxiety, depression, and burden; and (iv) ALS-related behavioral impairment. Spouses also provided mixed accounts of telehealth care, pointing out its convenience but some felt that face-to-face appointments were preferable.

CONCLUSIONS: While many reactions to the pandemic reported by spouses of pwALS may have been similar to those of the general population or other vulnerable groups, interviews indicated the potential for the pandemic to have made more apparent certain aspects of behavioral change in pwALS with which carers may require support. Clinicians need to acknowledge spouses' concerns about the potential limitations of remote clinical consultations, enquire about cognitive and behavioral change, and consider how input should be best provided in such limiting circumstances.}, } @article {pmid38719860, year = {2024}, author = {Cusaro, CM and Capelli, E and Picco, AM and Brusoni, M}, title = {Incidence of resistance to ALS and ACCase inhibitors in Echinochloa species and soil microbial composition in Northern Italy.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {10544}, pmid = {38719860}, issn = {2045-2322}, support = {ECS00000036//MUR - M4C2 1.5 of PNRR funded by the European Union - NextGenerationEU/ ; }, mesh = {*Soil Microbiology ; Italy/epidemiology ; *Herbicide Resistance ; *Herbicides/pharmacology ; *Acetolactate Synthase/antagonists & inhibitors/genetics ; *Echinochloa/drug effects ; *Acetyl-CoA Carboxylase/genetics/antagonists & inhibitors ; Plant Weeds/drug effects ; Microbiota/drug effects ; Biodiversity ; Bacteria/drug effects/genetics/isolation & purification/classification ; Soil/chemistry ; Fungi/drug effects/isolation & purification/genetics ; }, abstract = {The increasing amount of weeds surviving herbicide represents a very serious problem for crop management. The interaction between microbial community of soil and herbicide resistance, along with the potential evolutive consequences, are still poorly known and need to be investigated to better understand the impact on agricultural management. In our study, we analyzed the microbial composition of soils in 32 farms, located in the Northern Italy rice-growing area (Lombardy) with the aim to evaluate the relationship between the microbial composition and the incidence of resistance to acetolactate synthase (ALS) and acetyl-CoA carboxylase (ACCase) inhibiting herbicides in Echinochloa species. We observed that the coverage of weeds survived herbicide treatment was higher than 60% in paddy fields with a low microbial biodiversity and less than 5% in those with a high microbial biodiversity. Fungal communities showed a greater reduction in richness than Bacteria. In soils with a reduced microbial diversity, a significant increase of some bacterial and fungal orders (i.e. Lactobacillales, Malasseziales and Diaporthales) was observed. Interestingly, we identified two different microbial profiles linked to the two conditions: high incidence of herbicide resistance (H-HeR) and low incidence of herbicide resistance (L-HeR). Overall, the results we obtained allow us to make hypotheses on the greater or lesser probability of herbicide resistance occurrence based on the composition of the soil microbiome and especially on the degree of biodiversity of the microbial communities.}, } @article {pmid38718295, year = {2024}, author = {Huang, J and Fu, Y and Wang, A and Shi, K and Peng, Y and Yi, Y and Yu, R and Gao, J and Feng, J and Jiang, G and Song, Q and Jiang, J and Chen, H and Gao, X}, title = {Brain Delivery of Protein Therapeutics by Cell Matrix-Inspired Biomimetic Nanocarrier.}, journal = {Advanced materials (Deerfield Beach, Fla.)}, volume = {36}, number = {31}, pages = {e2405323}, doi = {10.1002/adma.202405323}, pmid = {38718295}, issn = {1521-4095}, support = {2022YFC2502800//National Key Research and Development Program of China/ ; 2023ZKZD21//Innovation Program of Shanghai Municipal Education Commission/ ; 81973272//National Natural Science Foundation of China/ ; 92068111//National Natural Science Foundation of China/ ; 81801212//National Natural Science Foundation of China/ ; 23S41900100//Shanghai Science and Technology Development Foundation/ ; 22QA1405000//Shanghai Science and Technology Development Foundation/ ; 21XD1422200//Shanghai Science and Technology Development Foundation/ ; SHSMU-ZDCX20211201//Innovative Research Team of High-Level Local Universities in Shanghai/ ; }, mesh = {Animals ; Mice ; *Biomimetic Materials/chemistry ; *Drug Carriers/chemistry ; *Blood-Brain Barrier/metabolism ; *Hyaluronic Acid/chemistry ; *Catalase/metabolism/chemistry ; *Brain/metabolism ; Nanoparticles/chemistry ; Protamines/chemistry ; Amyotrophic Lateral Sclerosis/drug therapy ; Disease Models, Animal ; Humans ; Brain Injuries/drug therapy/metabolism ; Biomimetics/methods ; }, abstract = {Protein therapeutics are anticipated to offer significant treatment options for central nervous system (CNS) diseases. However, the majority of proteins are unable to traverse the blood-brain barrier (BBB) and reach their CNS target sites. Inspired by the natural environment of active proteins, the cell matrix components hyaluronic acid (HA) and protamine (PRTM) are used to self-assemble with proteins to form a protein-loaded biomimetic core and then incorporated into ApoE3-reconstituted high-density lipoprotein (rHDL) to form a protein-loaded biomimetic nanocarrier (Protein-HA-PRTM-rHDL). This cell matrix-inspired biomimetic nanocarrier facilitates the penetration of protein therapeutics across the BBB and enables their access to intracellular target sites. Specifically, CAT-HA-PRTM-rHDL facilitates rapid intracellular delivery and release of catalase (CAT) via macropinocytosis-activated membrane fusion, resulting in improved spatial learning and memory in traumatic brain injury (TBI) model mice (significantly reduces the latency of TBI mice and doubles the number of crossing platforms), and enhances motor function and prolongs survival in amyotrophic lateral sclerosis (ALS) model mice (extended the median survival of ALS mice by more than 10 days). Collectively, this cell matrix-inspired nanoplatform enables the efficient CNS delivery of protein therapeutics and provides a novel approach for the treatment of CNS diseases.}, } @article {pmid38717990, year = {2024}, author = {Yu, X and Sun, J and Yang, Y and Zhang, J and Lu, Y and Tang, W}, title = {Enhanced Herbicide Metabolism and Target Site Mutation Enabled the Multiple Resistance to Cyhalofop-butyl, Florpyrauxifen-benzyl, and Penoxsulam in Echinochloa crus-galli.}, journal = {Journal of agricultural and food chemistry}, volume = {72}, number = {20}, pages = {11405-11414}, doi = {10.1021/acs.jafc.4c02450}, pmid = {38717990}, issn = {1520-5118}, mesh = {*Herbicide Resistance/genetics ; *Herbicides/pharmacology/metabolism ; *Mutation ; *Echinochloa/genetics/drug effects/metabolism/growth & development ; *Plant Proteins/genetics/metabolism ; *Cytochrome P-450 Enzyme System/genetics/metabolism ; Acetyl-CoA Carboxylase/genetics/metabolism ; Plant Weeds/drug effects/genetics/metabolism ; Acetolactate Synthase/genetics/metabolism ; Butanes ; Nitriles ; Sulfonamides ; Uridine/analogs & derivatives ; }, abstract = {This study investigated the multiple herbicide resistance (MHR) mechanism of one Echinochloa crus-galli population that was resistant to florpyrauxifen-benzyl (FPB), cyhalofop-butyl (CHB), and penoxsulam (PEX). This population carried an Ala-122-Asn mutation in the acetolactate synthase (ALS) gene but no mutation in acetyl-CoA carboxylase (ACCase) and transport inhibitor response1 (TIR1) genes. The metabolism rate of PEX was 2-fold higher, and the production of florpyrauxifen-acid and cyhalofop-acid was lower in the resistant population. Malathion and 4-chloro-7-nitrobenzoxadiazole (NBD-Cl) could reverse the resistance, suggesting that cytochrome P450 (CYP450) and glutathione S-transferase (GST) contribute to the enhanced metabolism. According to RNA-seq and qRT-PCR validation, two CYP450 genes (CYP71C42 and CYP71D55), one GST gene (GSTT2), two glycosyltransferase genes (rhamnosyltransferase 1 and IAAGLU), and two ABC transporter genes (ABCG1 and ABCG25) were induced by CHB, FPB, and PEX in the resistant population. This study revealed that the target mutant and enhanced metabolism were involved in the MHR mechanism in E. crus-galli.}, } @article {pmid38717875, year = {2024}, author = {Chen, M and Zhou, P}, title = {2CFastICA: A Novel Method for High Density Surface EMG Decomposition Based on Kernel Constrained FastICA and Correlation Constrained FastICA.}, journal = {IEEE transactions on neural systems and rehabilitation engineering : a publication of the IEEE Engineering in Medicine and Biology Society}, volume = {32}, number = {}, pages = {2177-2186}, doi = {10.1109/TNSRE.2024.3398822}, pmid = {38717875}, issn = {1558-0210}, mesh = {*Electromyography/methods ; Humans ; *Algorithms ; *Signal-To-Noise Ratio ; Reproducibility of Results ; Signal Processing, Computer-Assisted ; Muscle, Skeletal/physiology ; Motor Neurons/physiology ; Computer Simulation ; Male ; Adult ; Female ; }, abstract = {This study presents a novel high density surface electromyography (EMG) decomposition method, named as 2CFastICA, because it incorporates two key algorithms: kernel constrained FastICA and correlation constrained FastICA. The former focuses on overcoming the local convergence of FastICA without requiring the peel-off strategy used in the progressive FastICA peel-off (PFP) framework. The latter further refines the output of kernel constrained FastICA by correcting possible erroneous or missed spikes. The two constrained FastICA algorithms supplement each other to warrant the decomposition performance. The 2CFastICA method was validated using simulated surface EMG signals with different motor unit numbers and signal to noise ratios (SNRs). Two source validation was also performed by simultaneous high density surface EMG and intramuscular EMG recordings, showing a matching rate (MR) of (97.2 ± 3.5)% for 170 common motor units. In addition, a different form of two source validation was also conducted taking advantages of the high density surface EMG characteristics of patients with amyotrophic lateral sclerosis, showing a MR of (99.4 ± 0.9)% for 34 common motor units from interference and sparse datasets. Both simulation and experimental results indicate that 2CFastICA can achieve similar decomposition performance to PFP. However, the efficiency of decomposition can be greatly improved by 2CFastICA since the complex signal processing procedures associated with the peel-off strategy are not required any more. Along with this paper, we also provide the MATLAB open source code of 2CFastICA for high density surface EMG decomposition.}, } @article {pmid38717430, year = {2024}, author = {Boyce, D and Raymond, J and Larson, TC and Kirkland, E and Horton, DK and Mehta, P}, title = {What do you think caused your ALS? An analysis of the CDC national amyotrophic lateral sclerosis patient registry qualitative risk factor data using artificial intelligence and qualitative methodology.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {25}, number = {5-6}, pages = {615-624}, pmid = {38717430}, issn = {2167-9223}, support = {CC999999/ImCDC/Intramural CDC HHS/United States ; }, mesh = {*Amyotrophic Lateral Sclerosis/psychology/epidemiology ; Humans ; *Artificial Intelligence ; *Registries ; Male ; Female ; United States/epidemiology ; Risk Factors ; Middle Aged ; Centers for Disease Control and Prevention, U.S. ; Aged ; Adult ; Qualitative Research ; Natural Language Processing ; }, abstract = {OBJECTIVE: Amyotrophic lateral sclerosis (ALS) is an incurable, progressive neurodegenerative disease with a significant health burden and poorly understood etiology. This analysis assessed the narrative responses from 3,061 participants in the Centers for Disease Control and Prevention's National ALS Registry who answered the question, "What do you think caused your ALS?"

METHODS: Data analysis used qualitative methods and artificial intelligence (AI) using natural language processing (NLP), specifically, Bidirectional Encoder Representations from Transformers (BERT) to explore responses regarding participants' perceptions of the cause of their disease.

RESULTS: Both qualitative and AI analysis methods revealed several, often aligned themes, which pointed to perceived causes including genetic, environmental, and military exposures. However, the qualitative analysis revealed detailed themes and subthemes, providing a more comprehensive understanding of participants' perceptions. Although there were areas of alignment between AI and qualitative analysis, AI's broader categories did not capture the nuances discovered using the more traditional, qualitative approach. The qualitative analysis also revealed that the potential causes of ALS were described within narratives that sometimes indicate self-blame and other maladaptive coping mechanisms.

CONCLUSIONS: This analysis highlights the diverse range of factors that individuals with ALS consider as perceived causes for their disease. Understanding these perceptions can help clinicians to better support people living with ALS (PLWALS). The analysis highlights the benefits of using traditional qualitative methods to supplement or improve upon AI-based approaches. This rapidly evolving area of data science has the potential to remove barriers to accessing the rich narratives of people with lived experience.}, } @article {pmid38717009, year = {2024}, author = {Zhang, X and Sun, Y and Zhang, X and Shen, D and Shu, S and Yang, X and Liu, M and Cui, L and Liu, Q and Zhang, X}, title = {Genotype-phenotype association and functional analysis of hnRNPA1 mutations in amyotrophic lateral sclerosis.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {25}, number = {5-6}, pages = {600-607}, doi = {10.1080/21678421.2024.2346502}, pmid = {38717009}, issn = {2167-9223}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics ; *Heterogeneous Nuclear Ribonucleoprotein A1/genetics ; Male ; Middle Aged ; Female ; *Mutation/genetics ; *Genetic Association Studies/methods ; Adult ; Exome Sequencing ; Aged ; }, abstract = {BACKGROUND: Pathogenic variants in hnRNPA1 have been reported in amyotrophic lateral sclerosis (ALS) patients. However, studies on hnRNPA1 mutant spectrum and pathogenicity of variants were rare.

METHODS: We performed whole exome sequencing of ALS-associated genes and subsequent verification of rare variants in hnRNPA1 in our ALS patients. The hnRNPA1 mutations reported in literature were reviewed and combined with our results to determine the genotype-phenotype relationship. Functional analysis of the novel variant p.G195A was performed in vitro by transfection of mutant hnRNPA1 into 293T cell.

RESULTS: Among 207 ALS patients recruited, 3 rare hnRNPA1 variants were identified (mutant frequency 1.45%), including two recurrent mutations (p.P340S and p.G283R), and a novel rare variant p.G195A. In combination with previous reports, there are 27 ALS patients with 15 hnRNPA1 mutations identified. Disease onset age was 47.90 ± 1.52 years with predominant limb onset. The p.P340S mutation caused flail arm syndrome (FAS) in two independent families with extended life expectancy. The newly identified p.G195A mutation, lying at the start of the PrLD ("prion-like" domain)/LCD (low-complexity domain), causes local structural changes in 3D protein prediction. Upon sodium arsenite exposure, mutant hnRNPA1 retained in the nucleus but deficit of cytoplasmic G3BP1-positive stress granule clearance was observed. This is different from the p.P340S mutation which caused both cytoplasmic translocation and stress granule formation. No cytoplasmic TDP-43 translocation was observed.

CONCLUSION: Mutations in hnRNPA1 are overall minor in ALS patients. The p.P340S mutation is associated with manifestation of FAS. Mutations in LCD of hnRNPA1 cause stress granule misprocessing.}, } @article {pmid38716751, year = {2024}, author = {Schito, P and Manera, U and Russo, T and Cremona, G and Riboldi, E and Tettamanti, A and Agosta, F and Quattrini, A and Chiò, A and Filippi, M and Calvo, A and Riva, N}, title = {Use of the combination of spirometry, arterial blood gas analysis and overnight oximetry to predict the outcomes of patients affected by motor neuron disease: The Milan-Torin respiratory score (Mi-To-RS).}, journal = {European journal of neurology}, volume = {31}, number = {8}, pages = {e16316}, pmid = {38716751}, issn = {1468-1331}, support = {//Giovanni Marazzina Foundation/ ; }, mesh = {Humans ; Female ; Male ; Middle Aged ; Aged ; *Blood Gas Analysis/methods ; *Spirometry ; *Oximetry/methods ; *Motor Neuron Disease/blood/physiopathology/diagnosis ; Prognosis ; Retrospective Studies ; Adult ; }, abstract = {BACKGROUND AND PURPOSE: The use of multiple tests, including spirometry, arterial blood gas (ABG) analysis and overnight oximetry (OvOx), is highly recommended to monitor the respiratory function of patients with motor neuron disease (MND). In this study, we propose a composite score to simplify the respiratory management of MND patients and better stratify their prognosis.

MATERIALS AND METHODS: We screened the clinical charts of 471 non-ventilated MND patients referred to the Neuro-rehabilitation Unit of the San Raffaele Scientific Institute of Milan (January 2001-December 2019), collecting spirometric, ABG and OvOx parameters. To evaluate the prognostic role of each measurement, univariate Cox regression for death/tracheostomy was performed, and the variables associated with survival were selected to design a scoring system. Univariate and multivariate Cox regression analyses were then carried out to evaluate the prognostic role of the score. Finally, results were replicated in an independent cohort from the Turin ALS Center.

RESULTS: The study population included 450 patients. Six measurements were found to be significantly associated with survival and were selected to design a scoring system (maximum score = 8 points). Kaplan-Meier analysis showed significant stratification of survival and time to non-invasive mechanical ventilation adaptation according to score values, and multivariate analysis confirmed the independent effect of the respiratory score on survival of each cohort.

CONCLUSION: Forced vital capacity, ABG and OvOx parameters provide complementary information for the respiratory management and prognosis of MND patients and the combination of these parameters into a single score might help neurologists predict prognosis and guide decisions on the timing of the implementation of different diagnostic or therapeutic approaches.}, } @article {pmid38715656, year = {2024}, author = {Paul, S and Dansithong, W and Gandelman, M and Figueroa, KP and Scoles, DR and Pulst, SM}, title = {Cerebellar Micro-RNA Profile in a Mouse Model of Spinocerebellar Ataxia Type 2.}, journal = {Neurology. Genetics}, volume = {10}, number = {2}, pages = {e200144}, pmid = {38715656}, issn = {2376-7839}, support = {R35 NS127253/NS/NINDS NIH HHS/United States ; }, abstract = {BACKGROUND AND OBJECTIVES: Micro-RNAs (miRNAs) are critical for regulating the expression of genes in multiple neurodegenerative diseases, but miRNAs have not been investigated in spinocerebellar ataxia type 2 (SCA2). SCA2, a dominantly inherited progressive neurodegenerative polyglutamine (polyQ) disease, is caused by a CAG repeat expansion in the ataxin-2 (ATXN2) gene. In this study, we determined miRNA transcriptomes in SCA2-BAC-ATXN2[Q72] transgenic mice.

METHODS: We assessed the expression of miRNAs in SCA2 transgenic mouse cerebella using the HiSeq Illumina sequencer. We used the miRNA target filter tool in Qiagen Ingenuity Pathway Analysis (IPA) to identify target genes of differentially expressed miRNAs (DEmiRs) within in the SCA2 mouse transcriptomes and then performed pathway analyses.

RESULTS: Our analysis revealed significant changes in the expression levels of multiple miRNAs in mice with SCA2. We identified 81 DEmiRs in mice with SCA2, with 52 miRNAs upregulated and 29 miRNAs downregulated after onset of rotarod deficit. Subsequent IPA processing enabled us to establish connections between these DEmiRs and specific biological regulatory functions. Furthermore, by using the IPA miRNA target filter, we identified target genes of DEmiRs in the SCA2-BAC-ATXN2[Q72] transcriptome data set and demonstrated their significant impact on several biological functional and disease pathways.

DISCUSSION: Our study establishes the role of both DEmiRs and their targets in SCA2 pathogenesis. By expressing mutant ATXN2 under the control of its endogenous regulatory elements in the SCA2-BAC-ATXN2[Q72] mouse model, we identified a set of DEmiRs that are shared across multiple neurodegenerative diseases including other SCAs, Alzheimer disease (AD), Parkinson disease (PD), and amyotrophic lateral sclerosis (ALS). There was a significant overlap of both DEmiRs and their targets of BAC-ATXN2[Q72] transcriptomes in dysregulated pathways that characterize SCA2. This observation also extended to dysregulated pathways in ALS, AD, and PD. DEmiRs identified in this study may represent therapeutic targets for neurodegeneration or lead to biomarkers for characterizing various neurodegenerative diseases.}, } @article {pmid38713169, year = {2024}, author = {Nikel, LM and Talbot, K and Vahsen, BF}, title = {Recent insights from human induced pluripotent stem cell models into the role of microglia in amyotrophic lateral sclerosis.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {46}, number = {7}, pages = {e2400054}, doi = {10.1002/bies.202400054}, pmid = {38713169}, issn = {1521-1878}, support = {2023/MNDS/6400/753TALB//MND Scotland/ ; Talbot/Apr22/889-791/MNDA_/Motor Neurone Disease Association/United Kingdom ; }, mesh = {*Amyotrophic Lateral Sclerosis/pathology/metabolism/genetics ; *Induced Pluripotent Stem Cells/metabolism ; Humans ; *Microglia/metabolism/pathology ; *Motor Neurons/pathology/metabolism ; Coculture Techniques ; Animals ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease, primarily leading to the degeneration of motor neurons. The traditional focus on motor neuron-centric mechanisms has recently shifted towards understanding the contribution of non-neuronal cells, such as microglia, in ALS pathophysiology. Advances in induced pluripotent stem cell (iPSC) technology have enabled the generation of iPSC-derived microglia monocultures and co-cultures to investigate their role in ALS pathogenesis. Here, we briefly review the insights gained from these studies into the role of microglia in ALS. While iPSC-derived microglia monocultures have revealed intrinsic cellular dysfunction due to ALS-associated mutations, microglia-motor neuron co-culture studies have demonstrated neurotoxic effects of mutant microglia on motor neurons. Based on these findings, we briefly discuss currently unresolved questions and how they could be addressed in future studies. iPSC models hold promise for uncovering disease-relevant pathways in ALS and identifying potential therapeutic targets.}, } @article {pmid38712849, year = {2024}, author = {Ludolph, AC and Corcia, P and Desnuelle, C and Heiman-Patterson, T and Mora, JS and Mansfield, CD and Couratier, P}, title = {Categorization of the amyotrophic lateral sclerosis population via the clinical determinant of post-onset ΔFS for study design and medical practice.}, journal = {Muscle & nerve}, volume = {70}, number = {1}, pages = {36-41}, doi = {10.1002/mus.28101}, pmid = {38712849}, issn = {1097-4598}, support = {//AB Science/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis ; Clinical Trials as Topic/methods ; Disease Progression ; Outcome Assessment, Health Care/standards ; *Research Design ; Severity of Illness Index ; }, abstract = {The amyotrophic lateral sclerosis (ALS) functional rating scale-revised (ALSFRS-R) has become the most widely utilized measure of disease severity in patients with ALS, with change in ALSFRS-R from baseline being a trusted primary outcome measure in ALS clinical trials. This is despite the scale having several established limitations, and although alternative scales have been proposed, it is unlikely that these will displace ALSFRS-R in the foreseeable future. Here, we discuss the merits of delta FS (ΔFS), the slope or rate of ALSFRS-R decline over time, as a relevant tool for innovative ALS study design, with an as yet untapped potential for optimization of drug effectiveness and patient management. In our view, categorization of the ALS population via the clinical determinant of post-onset ΔFS is an important study design consideration. It serves not only as a critical stratification factor and basis for patient enrichment but also as a tool to explore differences in treatment response across the overall population; thereby, facilitating identification of responder subgroups. Moreover, because post-onset ΔFS is derived from information routinely collected as part of standard patient care and monitoring, it provides a suitable patient selection tool for treating physicians. Overall, post-onset ΔFS is a very attractive enrichment tool that is, can and should be regularly incorporated into ALS trial design.}, } @article {pmid38712174, year = {2025}, author = {Ozkan, A and Padmanabhan, HK and Shipman, SL and Azim, E and Kumar, P and Sadegh, C and Basak, AN and Macklis, JD}, title = {Directed differentiation of functional corticospinal-like neurons from endogenous SOX6+/NG2+ cortical progenitors.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2024.04.21.590488}, pmid = {38712174}, issn = {2692-8205}, support = {DP1 NS106665/NS/NINDS NIH HHS/United States ; R01 NS045523/NS/NINDS NIH HHS/United States ; R01 NS049553/NS/NINDS NIH HHS/United States ; }, abstract = {Corticospinal neurons (CSN) centrally degenerate in amyotrophic lateral sclerosis (ALS), along with spinal motor neurons, and loss of voluntary motor function in spinal cord injury (SCI) results from damage to CSN axons. For functional regeneration of specifically affected neuronal circuitry in vivo , or for optimally informative disease modeling and/or therapeutic screening in vitro , it is important to reproduce the type or subtype of neurons involved. No such appropriate in vitro models exist with which to investigate CSN selective vulnerability and degeneration in ALS, or to investigate routes to regeneration of CSN circuitry for ALS or SCI, critically limiting the relevance of much research. Here, we identify that the HMG-domain transcription factor Sox6 is expressed by a subset of NG2+ endogenous cortical progenitors in postnatal and adult cortex, and that Sox6 suppresses a latent neurogenic program by repressing proneural Neurog2 expression by progenitors. We FACS-purify these progenitors from postnatal mouse cortex and establish a culture system to investigate their potential for directed differentiation into CSN. We then employ a multi-component construct with complementary and differentiation-sharpening transcriptional controls (activating Neurog2, Fezf2 , while antagonizing Olig2 with VP16:Olig2). We generate corticospinal-like neurons from SOX6+/NG2+ cortical progenitors, and find that these neurons differentiate with remarkable fidelity compared with corticospinal neurons in vivo . They possess appropriate morphological, molecular, transcriptomic, and electrophysiological characteristics, without characteristics of the alternate intracortical or other neuronal subtypes. We identify that these critical specifics of differentiation are not reproduced by commonly employed Neurog2 -driven differentiation. Neurons induced by Neurog2 instead exhibit aberrant multi-axon morphology and express molecular hallmarks of alternate cortical projection subtypes, often in mixed form. Together, this developmentally-based directed differentiation from cortical progenitors sets a precedent and foundation for in vitro mechanistic and therapeutic disease modeling, and toward regenerative neuronal repopulation and circuit repair.}, } @article {pmid38712171, year = {2024}, author = {Islam, Z and Polash, A and Suzawa, M and Chim, B and Kuhn, S and Sultana, S and Cutrona, N and Smith, PT and Kabat, J and Ganesan, S and Foroushani, A and Hafner, M and Muljo, SA}, title = {MATRIN3 deficiency triggers autoinflammation via cGAS-STING activation.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {38712171}, issn = {2692-8205}, support = {ZIA AI001185/ImNIH/Intramural NIH HHS/United States ; ZIA AR041205/ImNIH/Intramural NIH HHS/United States ; }, abstract = {Interferon-stimulated genes (ISGs) comprise a program of immune effectors important for host immune defense. When uncontrolled, ISGs play a central role in interferonopathies and other inflammatory diseases. The mechanisms responsible for turning on ISGs are not completely known. By investigating MATRIN3 (MATR3), a nuclear RNA-binding protein mutated in familial ALS, we found that perturbing MATR3 results in elevated expression of ISGs. Using an integrative approach, we elucidate a pathway that leads to activation of cGAS-STING. This outlines a plausible mechanism for pathogenesis in a subset of ALS, and suggests new diagnostic and therapeutic approaches for this fatal disease.}, } @article {pmid38711658, year = {2024}, author = {Otero, G and Bolatto, C and Isasi, E and Cerri, S and Rodríguez, P and Boragno, D and Marco, M and Parada, C and Stancov, M and Cuitinho, MN and Olivera-Bravo, S}, title = {Adult aberrant astrocytes submitted to late passage cultivation lost differentiation markers and decreased their pro-inflammatory profile.}, journal = {Heliyon}, volume = {10}, number = {9}, pages = {e30360}, pmid = {38711658}, issn = {2405-8440}, abstract = {In amyotrophic lateral sclerosis (ALS), astrocytes are considered key players in some non-cell non-neuronal autonomous mechanisms that underlie motor neuron death. However, it is unknown how much of these deleterious features were permanently acquired. To assess this point, we evaluated if the most remarkable features of neurotoxic aberrant glial phenotypes (AbAs) isolated from paralytic rats of the ALS model G93A Cu/Zn superoxide dismutase 1 (SOD1) could remain upon long lasting cultivation. Real time PCR, immunolabelling and zymography analysis showed that upon many passages, AbAs preserved the cell proliferation capacity, mitochondrial function and response to different compounds that inhibit some key astrocyte functions but decreased the expression of parameters associated to cell lineage, homeostasis and inflammation. As these results are contrary to the sustained inflammatory status observed along disease progression in SOD1G93A rats, we propose that the most AbAs remarkable features related to homeostasis and neurotoxicity were not permanently acquired and might depend on the signaling coming from the injuring microenvironment present in the degenerating spinal cord of terminal rats.}, } @article {pmid38711616, year = {2024}, author = {Chen, L and Chen, G and Zhang, M and Zhang, X}, title = {Modeling sporadic juvenile ALS in iPSC-derived motor neurons explores the pathogenesis of FUS[R503fs] mutation.}, journal = {Frontiers in cellular neuroscience}, volume = {18}, number = {}, pages = {1364164}, pmid = {38711616}, issn = {1662-5102}, abstract = {INTRODUCTION: Fused in sarcoma (FUS) mutations represent the most common genetic etiology of juvenile amyotrophic lateral sclerosis (JALS), for which effective treatments are lacking. In a prior report, we identified a novel FUS mutation, c.1509dupA: p. R503fs (FUSR503fs), in a sporadic JALS patient.

METHODS: The physicochemical properties and structure of FUSR503fs protein were analyzed by software: Multi-electrode array (MEA) assay, calcium activity imaging assay and transcriptome analysis were used to explore the pathophysiological mechanism of iPSC derived motor neurons.

RESULTS: Structural analysis and predictions regarding physical and chemical properties of this mutation suggest that the reduction of phosphorylation and glycosylation sites, along with alterations in the amino acid sequence, may contribute to abnormal FUS accumulation within the cytoplasm and nucleus of induced pluripotent stem cell- derived motor neurons (MNs). Multi-electrode array and calcium activity imaging indicate diminished spontaneous electrical and calcium activity signals in MNs harboring the FUS[R503fs] mutation. Transcriptomic analysis reveals upregulation of genes associated with viral infection and downregulation of genes involved in neural function maintenance, such as the ATP6V1C2 gene. Treatment with ropinirole marginally mitigates the electrophysiological decline in FUS[R503fs] MNs, suggesting the utility of this cell model for mechanistic exploration and drug screening.

DISCUSSION: iPSCs-derived motor neurons from JALS patients are promising tools for drug screening. The pathological changes in motor neurons of FUS[R503fs] may occur earlier than in other known mutation types that have been reported.}, } @article {pmid38711277, year = {2024}, author = {Vakilipour, P and Fekrvand, S}, title = {Brain-to-brain interface technology: A brief history, current state, and future goals.}, journal = {International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience}, volume = {84}, number = {5}, pages = {351-367}, doi = {10.1002/jdn.10334}, pmid = {38711277}, issn = {1873-474X}, mesh = {Humans ; *Brain-Computer Interfaces ; *Brain/physiology ; History, 20th Century ; History, 21st Century ; }, abstract = {A brain-to-brain interface (BBI), defined as a combination of neuroimaging and neurostimulation methods to extract and deliver information between brains directly without the need for the peripheral nervous system, is a budding communication technique. A BBI system is made up of two parts known as the brain-computer interface part, which reads a sender's brain activity and digitalizes it, and the computer-brain interface part, which writes the delivered brain activity to a receiving brain. As with other technologies, BBI systems have gone through an evolutionary process since they first appeared. The BBI systems have been employed for numerous purposes, including rehabilitation for post-stroke patients, communicating with patients suffering from amyotrophic lateral sclerosis, locked-in syndrome and speech problems following stroke. Also, it has been proposed that a BBI system could play an important role on future battlefields. This technology was not only employed for communicating between two human brains but also for making a direct communication path among different species through which motor or sensory commands could be sent and received. However, the application of BBI systems has provoked significant challenges to human rights principles due to their ability to access and manipulate human brain information. In this study, we aimed to review the brain-computer interface and computer-brain interface technologies as components of BBI systems, the development of BBI systems, applications of this technology, arising ethical issues and expectations for future use.}, } @article {pmid38711257, year = {2024}, author = {Horty, LG and Martin, T}, title = {Synthesis of Radiolabeled [[14]C]Rimsulfuron and Stable Isotope Labeled Rimsulfuron-[M + 3] to Support Crop Metabolism Studies for Reregistration.}, journal = {Journal of labelled compounds & radiopharmaceuticals}, volume = {67}, number = {7}, pages = {263-272}, doi = {10.1002/jlcr.4096}, pmid = {38711257}, issn = {1099-1344}, mesh = {*Carbon Radioisotopes/chemistry ; *Crops, Agricultural/metabolism ; *Isotope Labeling ; *Pyridines/chemistry/chemical synthesis ; Herbicides/chemical synthesis/chemistry ; Sulfonamides ; }, abstract = {Rimsulfuron is a sulfonylurea herbicide that controls grass and broadleaf weeds in maize, potatoes, fruits, nuts, and other crops. It can also be used as a burndown herbicide to clear invasive weed species along roadsides and other nonagricultural land. Rimsulfuron acts as an acetolactase synthase (ALS) inhibitor, blocking the synthesis of essential amino acids required for plant growth. As is common practice, rimsulfuron has been subject to periodic reviews by regulatory agencies for reregistration since its introduction into the market in the early 1990s. The goal of these reviews is to ensure that the herbicide carries out its intended use without creating adverse side effects to humans and the environment. Since scientific methods are continually evolving and being developed, global regulatory agencies can require additional studies to address data gaps for pesticide renewals. During this reregistration process for rimsulfuron, a new confined rotational crop study was required to address a data gap requested by the European Food Safety Authority (EFSA). Consequently, the corresponding pyridine and pyrimidine radiolabeled [[14]C]rimsulfuron and [M + 3] stable isotopes of rimsulfuron were synthesized for this study to support the reregistration process.}, } @article {pmid38709603, year = {2024}, author = {Demaree, D and Brignone, J and Bromberg, M and Zhang, H}, title = {Preliminary Study on Effects of Neck Exoskeleton Structural Design in Patients With Amyotrophic Lateral Sclerosis.}, journal = {IEEE transactions on neural systems and rehabilitation engineering : a publication of the IEEE Engineering in Medicine and Biology Society}, volume = {32}, number = {}, pages = {1841-1850}, doi = {10.1109/TNSRE.2024.3397584}, pmid = {38709603}, issn = {1558-0210}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology ; Male ; *Exoskeleton Device ; Female ; Middle Aged ; *Neck Muscles/physiopathology ; Biomechanical Phenomena ; Aged ; Electromyography ; Head Movements ; Neck/physiopathology ; Equipment Design ; Adult ; Muscle Weakness/physiopathology ; }, abstract = {Neck muscle weakness due to amyotrophic lateral sclerosis (ALS) can result in dropped head syndrome, adversely impacting the quality of life of those affected. Static neck collars are currently prescribed to hold the head in a fixed upright position. However, these braces are uncomfortable and do not allow any voluntary head-neck movements. By contrast, powered neck exoskeletons have the potential to enable head-neck movements. Our group has recently improved the mechanical structure of a state-of-the-art neck exoskeleton through a weighted optimization. To evaluate the effect of the structural changes, we conducted an experiment in which patients with ALS were asked to perform head-neck tracking tasks while using the two versions of the neck exoskeleton. We found that the neck muscle activation was significantly reduced when assisted by the structurally enhanced design compared to no assistance provided. The improved structure also improved kinematics tracking performance, allowing users to better achieve the desired head poses. In comparison, the previous design did not help reduce the muscle effort required to perform these tasks and even slightly worsened the kinematic tracking performance. It was also found that biomechanical benefits gained from using the structurally improved design were consistent across participants with both mild and severe neck weakness. Furthermore, we observed that participants preferred to use the powered neck exoskeletons to voluntarily move their heads and make eye contact during a conversation task rather than remain in a fixed upright position. Each of these findings highlights the importance of the structural design of neck exoskeletons in achieving desired biomechanical benefits and suggests that neck exoskeletons can be a viable method to improve the daily life of patients with ALS.}, } @article {pmid38709037, year = {2024}, author = {Ketabforoush, A and Wang, M and Smith, CL and Arnold, WD and Nichols, NL}, title = {Assessing Rat Diaphragm Motor Unit Connectivity Outcome Measures as Quantitative Biomarkers of Phrenic Motor Neuron Degeneration and Compensation.}, journal = {Journal of visualized experiments : JoVE}, volume = {}, number = {206}, pages = {}, doi = {10.3791/66568}, pmid = {38709037}, issn = {1940-087X}, mesh = {Animals ; *Motor Neurons/pathology ; Rats ; *Phrenic Nerve ; *Diaphragm/innervation/physiopathology ; Biomarkers/analysis/metabolism ; Action Potentials/physiology ; Nerve Degeneration/pathology ; Rats, Sprague-Dawley ; }, abstract = {Loss of ventilatory muscle function is a consequence of motor neuron injury and neurodegeneration (e.g., cervical spinal cord injury and amyotrophic lateral sclerosis, respectively). Phrenic motor neurons are the final link between the central nervous system and muscle, and their respective motor units (groups of muscle fibers innervated by a single motor neuron) represent the smallest functional unit of the neuromuscular ventilatory system. Compound muscle action potential (CMAP), single motor unit potential (SMUP), and motor unit number estimation (MUNE) are established electrophysiological approaches that enable the longitudinal assessment of motor unit integrity in animal models over time but have mostly been applied to limb muscles. Therefore, the objectives of this study are to describe an approach in preclinical rodent studies that can be used longitudinally to quantify the phrenic MUNE, motor unit size (represented as SMUP), and CMAP, and then to demonstrate the utility of these approaches in a motor neuron loss model. Sensitive, objective, and translationally relevant biomarkers for neuronal injury, degeneration, and regeneration in motor neuron injury and diseases can significantly aid and accelerate experimental research discoveries to clinical testing.}, } @article {pmid38708921, year = {2024}, author = {Monteiro, KLC and Dos Santos Alcântara, MG and de Aquino, TM and da Silva-Júnior, EF}, title = {Insights on Natural Products Against Amyotrophic Lateral Sclerosis (ALS).}, journal = {Current neuropharmacology}, volume = {22}, number = {7}, pages = {1169-1188}, pmid = {38708921}, issn = {1875-6190}, mesh = {*Amyotrophic Lateral Sclerosis/drug therapy ; Humans ; *Biological Products/therapeutic use/pharmacology ; Animals ; Neuroprotective Agents/therapeutic use/pharmacology ; Plants, Medicinal/chemistry ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that causes the death of motor neurons and consequent muscle paralysis. Despite many efforts to address it, current therapy targeting ALS remains limited, increasing the interest in complementary therapies. Over the years, several herbal preparations and medicinal plants have been studied to prevent and treat this disease, which has received remarkable attention due to their blood-brain barrier penetration properties and low toxicity. Thus, this review presents the therapeutic potential of a variety of medicinal herbs and their relationship with ALS and their physiopathological pathways.}, } @article {pmid38708063, year = {2024}, author = {Maria, B and Massimo, G and Antonio, B and Giuseppe, S and Giovanna, BE}, title = {BerTime: A novel tool for supporting ALS algorithm application in clinical practice.}, journal = {Resuscitation plus}, volume = {18}, number = {}, pages = {100636}, pmid = {38708063}, issn = {2666-5204}, } @article {pmid38706964, year = {2024}, author = {Edman, S and Horwath, O and Van der Stede, T and Blackwood, SJ and Moberg, I and Strömlind, H and Nordström, F and Ekblom, M and Katz, A and Apró, W and Moberg, M}, title = {Pro-Brain-Derived Neurotrophic Factor (BDNF), but Not Mature BDNF, Is Expressed in Human Skeletal Muscle: Implications for Exercise-Induced Neuroplasticity.}, journal = {Function (Oxford, England)}, volume = {5}, number = {3}, pages = {zqae005}, pmid = {38706964}, issn = {2633-8823}, mesh = {Adult ; Female ; Humans ; Male ; Young Adult ; *Brain-Derived Neurotrophic Factor/metabolism/blood ; *Exercise/physiology ; Lactic Acid/blood/metabolism ; *Muscle, Skeletal/metabolism ; *Neuronal Plasticity ; Protein Precursors/metabolism ; }, abstract = {Exercise promotes brain plasticity partly by stimulating increases in mature brain-derived neurotrophic factor (mBDNF), but the role of the pro-BDNF isoform in the regulation of BDNF metabolism in humans is unknown. We quantified the expression of pro-BDNF and mBDNF in human skeletal muscle and plasma at rest, after acute exercise (+/- lactate infusion), and after fasting. Pro-BDNF and mBDNF were analyzed with immunoblotting, enzyme-linked immunosorbent assay, immunohistochemistry, and quantitative polymerase chain reaction. Pro-BDNF was consistently and clearly detected in skeletal muscle (40-250 pg mg[-1] dry muscle), whereas mBDNF was not. All methods showed a 4-fold greater pro-BDNF expression in type I muscle fibers compared to type II fibers. Exercise resulted in elevated plasma levels of mBDNF (55%) and pro-BDNF (20%), as well as muscle levels of pro-BDNF (∼10%, all P < 0.05). Lactate infusion during exercise induced a significantly greater increase in plasma mBDNF (115%, P < 0.05) compared to control (saline infusion), with no effect on pro-BDNF levels in plasma or muscle. A 3-day fast resulted in a small increase in plasma pro-BDNF (∼10%, P < 0.05), with no effect on mBDNF. Pro-BDNF is highly expressed in human skeletal muscle, particularly in type I fibers, and is increased after exercise. While exercising with higher lactate augmented levels of plasma mBDNF, exercise-mediated increases in circulating mBDNF likely derive partly from release and cleavage of pro-BDNF from skeletal muscle, and partly from neural and other tissues. These findings have implications for preclinical and clinical work related to a wide range of neurological disorders such as Alzheimer's, clinical depression, and amyotrophic lateral sclerosis.}, } @article {pmid38706539, year = {2024}, author = {Rungan, S and Smith-Merry, J and Liu, HM and Drinkwater, A and Eastwood, J}, title = {School-Based Integrated Care Within Sydney Local Health District: A Qualitative Study About Partnerships Between the Education and Health Sectors.}, journal = {International journal of integrated care}, volume = {24}, number = {2}, pages = {13}, pmid = {38706539}, issn = {1568-4156}, abstract = {INTRODUCTION: The unmet physical and mental health needs of school-aged children (5-18 years) in New South Wales (NSW), stemming from poor access and engagement with healthcare, can be addressed by school-based integrated care (SBIC) models.This research aims to understand why and how partnerships between the health and education sector, in SBIC models, are important in providing care for children, and to identify the facilitating factors and barriers for implementation.

METHODS: A qualitative study was conducted using semi-structured interviews and thematic analysis. The principles of the 'Integrated People-Centred Health Service (IPCHS)' framework and Looman et al's (2021) implementation strategies for integrated care were considered.

RESULTS: Themes within IPCHS framework: Strategy 1: Engaging and empowering people and communities - community-driven models, improved access to healthcare, positive outcomes for children and families, 'connection', and service provision for marginalised populations; Strategy 2: Strengthening governance and accountability - system integration and developing evidence base; Strategy 3: Reorienting the model of care - shifting healthcare to schools reduces inequity and provides culturally safe practice; Strategy 4: Coordinating services within and across sectors - integrating care and stable workforce; Strategy 5: Creating an enabling environment: leadership, stakeholder commitment, and adequate resourcing.

DISCUSSION: Potential strategies for implementing SBIC models across NSW include community consultation and co-design; building multidisciplinary teams with new competencies and roles e.g. linkers and coordinators; collaborative and shared leadership; and alignment of operational systems while maintaining a balance between structure and flexibility.

CONCLUSION: SBIC models require high-level collaboration across sectors and with communities to provide a shift towards child and family centred care that improves engagement, access and outcomes in health delivery.}, } @article {pmid38705796, year = {2024}, author = {Grangeon, L and Wallon, D and Bourre, B and Guillaume, M and Guegan-Massardier, E and Guyant-Marechal, L and Liard, A and Sibert, L and Maltete, D}, title = {Development of an Objective Structured Clinical Examination (OSCE) to evaluate the diagnosis announcement of chronic neurological disease by residents in neurology.}, journal = {Revue neurologique}, volume = {180}, number = {7}, pages = {655-660}, doi = {10.1016/j.neurol.2024.02.390}, pmid = {38705796}, issn = {0035-3787}, mesh = {Humans ; *Neurology/standards/education ; *Internship and Residency/standards ; *Nervous System Diseases/diagnosis ; *Educational Measurement/methods ; Chronic Disease ; Male ; Female ; Adult ; Clinical Competence/standards ; Prospective Studies ; Surveys and Questionnaires ; }, abstract = {BACKGROUND: There is little consensus on how to make a diagnosis announcement of severe chronic disease in neurology. Other medical specialties, such as oncology, have developed assessment methods similar to the Objective Structured Clinical Examination (OSCE) to address this issue. Here we report the implementation of an OSCE focused on the diagnosis announcement of chronic disease in neurology by residents.

OBJECTIVE: We aimed to evaluate the acceptability, feasibility and validity in routine practice of an OSCE combined with a theoretical course focused on diagnosis announcement in neurology.

METHOD: Eighteen neurology residents were prospectively included between 2019 and 2022. First, they answered a questionnaire on their previous level of training in diagnosis announcement. Second, in a practical session with a simulated patient, they made a 15-min diagnosis announcement and then had 5mins of immediate feedback with an expert observer, present in the room. The OSCE consisted of 4 different stations, with standardized scenarios dedicated to the announcement of multiple sclerosis (MS), Parkinson's disease (PD), Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS). Third, in a theory session, expert observers covered the essential theoretical points. All residents and expert observers completed an evaluation of the "practical session" and the "theory session".

RESULTS: Residents estimated their previous level of diagnosis announcement training at 3.1/5. The most feared announcements were AD and ALS. The "practical session" was rated at a mean of 4.1/5 by the residents and 4.8/5 by the expert observers, and the "theory session" at a mean of 4.7/5 by the residents and 5/5 by the expert observers. After the OSCEs, 11 residents felt more confident about making an announcement.

CONCLUSION: This study has shown a benefit of using an OSCE to learn how to make a diagnosis announcement of severe chronic disease in neurology. OSCEs could be used in many departments in routine practice and seem adapted to residents.}, } @article {pmid38705786, year = {2024}, author = {Ishikawa, A and Takeda, T and Kokubun, S and Saito, Y and Isose, S and Ito, K and Arai, K and Sugiyama, A and Kuwabara, S and Honda, K}, title = {Putaminal hypointensity on T2-weighted MRI mimicking multiple system atrophy in amyotrophic lateral sclerosis: An autopsy case report.}, journal = {Journal of the neurological sciences}, volume = {460}, number = {}, pages = {123025}, doi = {10.1016/j.jns.2024.123025}, pmid = {38705786}, issn = {1878-5883}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnostic imaging/pathology ; *Multiple System Atrophy/diagnostic imaging/pathology ; *Magnetic Resonance Imaging ; *Autopsy ; Putamen/diagnostic imaging/pathology ; Male ; Diagnosis, Differential ; Middle Aged ; Aged ; Female ; }, } @article {pmid38705318, year = {2024}, author = {Mororó, MCC and Mahnke, LC and Assis, CRD and da Silva, RA and Cabrera, MP and Bezerra, RP and Carvalho Júnior, LB and Alves, MHME}, title = {Acetylcholinesterase purification from human erythrocytes using magnetic nanoparticles containing procainamide.}, journal = {International journal of biological macromolecules}, volume = {269}, number = {Pt 1}, pages = {132094}, doi = {10.1016/j.ijbiomac.2024.132094}, pmid = {38705318}, issn = {1879-0003}, mesh = {Humans ; *Acetylcholinesterase/chemistry/metabolism/isolation & purification ; *Erythrocytes/enzymology ; *Magnetite Nanoparticles/chemistry ; *Procainamide/chemistry ; Aniline Compounds/chemistry ; }, abstract = {This work presents a magnetic purification method of human erythrocyte Acetylcholinesterase (EC 3.1.1.7; AChE) based on affinity binding to procainamide (Proca) as ligand. Acetylcholinesterase is an acetylcholine-regulating enzyme found in different areas of the body and associated with various neurological disorders, such as Parkinson, Alzheymer and Amyotrophic Lateral Sclerosis. AChE from human erythrocyte purification has been attempted in recent years with low degree of purity. Here, magnetic nanoparticles (MNP) were synthesized and coated with polyaniline (PANI) and procainamide (PROCA) was covalently linked to the PANI. The extracted human erythrocyte AChE formed a complex with the MNP@PANI-PROCA and an external magnet separated it from the undesired proteins. Finally, the enzyme was collected by increasing the ionic strength. Experimental Box-Behnken design was developed to optimize this process of human erythrocyte AChE purification protocol. The enzyme was purified in all fifteen experiments. However, the best AChE purification result was achieved, about 2000 times purified, when 100 mg of MNP@PANI-PROCA was incubated for one hour with 4 ml hemolysate extract. The SDS-PAGE of this preparation presented a molecular weight of approximately 70 kDa, corroborating with few previous studies of AChE from erythrocyte purification.}, } @article {pmid38705104, year = {2024}, author = {Dharmadasa, T and Pavey, N and Tu, S and Menon, P and Huynh, W and Mahoney, CJ and Timmins, HC and Higashihara, M and van den Bos, M and Shibuya, K and Kuwabara, S and Grosskreutz, J and Kiernan, MC and Vucic, S}, title = {Novel approaches to assessing upper motor neuron dysfunction in motor neuron disease/amyotrophic lateral sclerosis: IFCN handbook chapter.}, journal = {Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology}, volume = {163}, number = {}, pages = {68-89}, doi = {10.1016/j.clinph.2024.04.010}, pmid = {38705104}, issn = {1872-8952}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology/diagnosis ; *Transcranial Magnetic Stimulation/methods ; *Motor Neuron Disease/physiopathology/diagnosis ; *Motor Neurons/physiology ; Evoked Potentials, Motor/physiology ; Motor Cortex/physiopathology/diagnostic imaging ; }, abstract = {Identifying upper motor neuron (UMN) dysfunction is fundamental to the diagnosis and understanding of disease pathogenesis in motor neuron disease (MND). The clinical assessment of UMN dysfunction may be difficult, particularly in the setting of severe muscle weakness. From a physiological perspective, transcranial magnetic stimulation (TMS) techniques provide objective biomarkers of UMN dysfunction in MND and may also be useful to interrogate cortical and network function. Single, paired- and triple pulse TMS techniques have yielded novel diagnostic and prognostic biomarkers in MND, and have provided important pathogenic insights, particularly pertaining to site of disease onset. Cortical hyperexcitability, as heralded by reduced short interval intracortical inhibition (SICI) and increased short interval intracortical facilitation, has been associated with the onset of lower motor neuron degeneration, along with patterns of disease spread, development of specific clinical features such as the split hand phenomenon, and may provide an indication about the rate of disease progression. Additionally, reduction of SICI has emerged as a potential diagnostic aid in MND. The triple stimulation technique (TST) was shown to enhance the diagnostic utility of conventional TMS measures in detecting UMN dysfunction in MND. Separately, sophisticated brain imaging techniques have uncovered novel biomarkers of neurodegeneration that have bene associated with progression. The present review will discuss the utility of TMS and brain neuroimaging derived biomarkers of UMN dysfunction in MND, focusing on recently developed TMS techniques and advanced neuroimaging modalities that interrogate structural and functional integrity of the corticomotoneuronal system, with an emphasis on pathogenic, diagnostic, and prognostic utility.}, } @article {pmid38703766, year = {2024}, author = {Alfahel, L and Gschwendtberger, T and Kozareva, V and Dumas, L and Gibbs, R and Kertser, A and Baruch, K and Zaccai, S and Kahn, J and Thau-Habermann, N and Eggenschwiler, R and Sterneckert, J and Hermann, A and Sundararaman, N and Vaibhav, V and Van Eyk, JE and Rafuse, VF and Fraenkel, E and Cantz, T and Petri, S and Israelson, A}, title = {Targeting low levels of MIF expression as a potential therapeutic strategy for ALS.}, journal = {Cell reports. Medicine}, volume = {5}, number = {5}, pages = {101546}, pmid = {38703766}, issn = {2666-3791}, mesh = {*Macrophage Migration-Inhibitory Factors/metabolism/genetics ; *Amyotrophic Lateral Sclerosis/metabolism/genetics/therapy/pathology ; Animals ; Humans ; *Motor Neurons/metabolism/pathology ; *Superoxide Dismutase-1/genetics/metabolism ; Mice ; Induced Pluripotent Stem Cells/metabolism ; Intramolecular Oxidoreductases/metabolism/genetics ; Mice, Transgenic ; Dependovirus/genetics ; Disease Models, Animal ; Male ; Mutation/genetics ; Female ; Protein Folding ; }, abstract = {Mutations in SOD1 cause amyotrophic lateral sclerosis (ALS), a neurodegenerative disease characterized by motor neuron (MN) loss. We previously discovered that macrophage migration inhibitory factor (MIF), whose levels are extremely low in spinal MNs, inhibits mutant SOD1 misfolding and toxicity. In this study, we show that a single peripheral injection of adeno-associated virus (AAV) delivering MIF into adult SOD1[G37R] mice significantly improves their motor function, delays disease progression, and extends survival. Moreover, MIF treatment reduces neuroinflammation and misfolded SOD1 accumulation, rescues MNs, and corrects dysregulated pathways as observed by proteomics and transcriptomics. Furthermore, we reveal low MIF levels in human induced pluripotent stem cell-derived MNs from familial ALS patients with different genetic mutations, as well as in post mortem tissues of sporadic ALS patients. Our findings indicate that peripheral MIF administration may provide a potential therapeutic mechanism for modulating misfolded SOD1 in vivo and disease outcome in ALS patients.}, } @article {pmid38703699, year = {2024}, author = {Grapperon, AM and Harlay, V and Boucekine, M and Devos, D and Rolland, AS and Desnuelle, C and Delmont, E and Verschueren, A and Attarian, S}, title = {Could the motor unit number index be an early prognostic biomarker for amyotrophic lateral sclerosis?.}, journal = {Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology}, volume = {163}, number = {}, pages = {47-55}, doi = {10.1016/j.clinph.2024.04.013}, pmid = {38703699}, issn = {1872-8952}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology/mortality/diagnosis ; Male ; Female ; Middle Aged ; Aged ; Longitudinal Studies ; *Motor Neurons/physiology ; Prognosis ; *Disease Progression ; Biomarkers ; Adult ; Electromyography ; }, abstract = {OBJECTIVE: To evaluate the associations between motor unit number index (MUNIX) and disease progression and prognosis in amyotrophic lateral sclerosis (ALS) in a large-scale longitudinal study.

METHODS: MUNIX was performed at the patient's first visit, at 3, 6, and 12 months in 4 muscles. MUNIX data from the patients were compared with those from 38 age-matched healthy controls. Clinical data included the revised ALS functional rating scale (ALSFRS-R), the forced vital capacity (FVC), and the survival of the patients.

RESULTS: Eighty-two patients were included at baseline, 62 were evaluated at three months, 48 at six months, and 33 at twelve months. MUNIX score was lower in ALS patients compared to controls. At baseline, MUNIX was correlated with ALSFRS-R and FVC. Motor unit size index (MUSIX) was correlated with patient survival. Longitudinal analyses showed that MUNIX decline was greater than ALSFRS-R decline at each evaluation. A baseline MUNIX score greater than 378 predicted survival over the 12-month period with a sensitivity of 82% and a specificity of 56%.

CONCLUSIONS: This longitudinal study suggests that MUNIX could be an early quantitative marker of disease progression and prognosis in ALS.

SIGNIFICANCE: MUNIX might be considered as potential indicator for monitoring disease progression.}, } @article {pmid38703513, year = {2024}, author = {El Khalfi, R and Maupoint, E and Chiavassa-Gandois, H and Goumarre, C and Filliole, A and Lapègue, F and Fabry, V and Acket, B and Laforet, A and Sans, N and Cintas, P and Faruch-Bilfeld, M}, title = {Assessment of whole-body muscle MRI for the early diagnosis of Amyotrophic Lateral Sclerosis.}, journal = {European journal of radiology}, volume = {176}, number = {}, pages = {111481}, doi = {10.1016/j.ejrad.2024.111481}, pmid = {38703513}, issn = {1872-7727}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnostic imaging ; Male ; Female ; Middle Aged ; *Whole Body Imaging/methods ; *Muscle, Skeletal/diagnostic imaging/pathology ; *Sensitivity and Specificity ; *Early Diagnosis ; *Magnetic Resonance Imaging/methods ; Reproducibility of Results ; Adult ; Aged ; }, abstract = {OBJECTIVES: To evaluate muscle signal abnormalities on whole-body muscle MRI with T2 and diffusion-weighted imaging in early ALS stages.

METHODS: 101 muscles were analyzed in newly diagnosed ALS patients and healthy controls on a whole-body MRI protocol including four-point T2-Dixon imaging and diffusion-weighted imaging (b0 and b800). Sensitivity and inter-observer agreement were assessed.

RESULTS: 15 patients (mean age, 64 +/- 12 [SD], 9 men) who met the Awaji-Shima criteria for definite, probable or possible ALS and 9 healthy controls were assessed (mean age, 53 +/- 13 [SD], 2 men). 61 % of the muscles assessed in ALS patients (62/101) showed signal hyperintensities on T2-weighted imaging, mainly in the upper and lower extremities (legs, hands and feet). ALS patients had a significantly higher number of involved muscles compared to healthy controls (p = 0,006). Diffusion-weighted imaging allowed for the detection of additional involvement in 22 muscles, thus improving the sensitivity of whole-body MRI from 60 % (using T2-weighted imaging only) up to 80 % (with the combination of T2-weighted and diffusion-weighted imaging).

CONCLUSIONS: ALS patients exhibited significant muscle signal abnormalities on T2-weighted and diffusion-weighted imaging in early disease stages. Whole-body MRI could be used for pre-EMG mapping of muscle involvement in order to choose suitable targets, thus improving early diagnosis.}, } @article {pmid38703371, year = {2024}, author = {Thumbadoo, KM and Dieriks, BV and Murray, HC and Swanson, MEV and Yoo, JH and Mehrabi, NF and Turner, C and Dragunow, M and Faull, RLM and Curtis, MA and Siddique, T and Shaw, CE and Newell, KL and Henden, L and Williams, KL and Nicholson, GA and Scotter, EL}, title = {Hippocampal aggregation signatures of pathogenic UBQLN2 in amyotrophic lateral sclerosis and frontotemporal dementia.}, journal = {Brain : a journal of neurology}, volume = {147}, number = {10}, pages = {3547-3561}, pmid = {38703371}, issn = {1460-2156}, support = {//Amelia Pais-Rodriguez and Marcus Gerbich/ ; 16420//Michael J Fox Foundation/ ; //Health Research Council Sir Charles Hercus Health Research Fellowship/ ; //Marsden FastStart and Rutherford Discovery Fellowship/ ; 15-UOA-157//Royal Society of New Zealand/ ; //Alzheimer's Disease Research and Education/ ; //Sir Thomas and Lady Duncan Trust/ ; //Coker Family Trust/ ; 2011120//National Health and Medical Research Council of Australia/ ; //Neuron Disease NZ/ ; //Freemasons Foundation of New Zealand/ ; //Matteo de Nora/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/genetics/pathology/metabolism ; *Frontotemporal Dementia/genetics/pathology/metabolism ; Humans ; *Autophagy-Related Proteins/genetics/metabolism ; *Hippocampus/pathology/metabolism ; Male ; *Adaptor Proteins, Signal Transducing/genetics/metabolism ; Middle Aged ; Female ; Aged ; DNA-Binding Proteins/genetics/metabolism ; Adult ; C9orf72 Protein/genetics ; Cell Cycle Proteins/genetics/metabolism ; }, abstract = {Pathogenic variants in the UBQLN2 gene cause X-linked dominant amyotrophic lateral sclerosis and/or frontotemporal dementia characterized by ubiquilin 2 aggregates in neurons of the motor cortex, hippocampus and spinal cord. However, ubiquilin 2 neuropathology is also seen in sporadic and familial amyotrophic lateral sclerosis and/or frontotemporal dementia cases not caused by UBQLN2 pathogenic variants, particularly C9orf72-linked cases. This makes the mechanistic role of mutant ubiquilin 2 protein and the value of ubiquilin 2 pathology for predicting genotype unclear. Here we examine a cohort of 44 genotypically diverse amyotrophic lateral sclerosis cases with or without frontotemporal dementia, including eight cases with UBQLN2 variants [resulting in p.S222G, p.P497H, p.P506S, p.T487I (two cases) and p.P497L (three cases)]. Using multiplexed (five-label) fluorescent immunohistochemistry, we mapped the co-localization of ubiquilin 2 with phosphorylated TDP-43, dipeptide repeat aggregates and p62 in the hippocampus of controls (n = 6), or amyotrophic lateral sclerosis with or without frontotemporal dementia in sporadic (n = 20), unknown familial (n = 3), SOD1-linked (n = 1), FUS-linked (n = 1), C9orf72-linked (n = 5) and UBQLN2-linked (n = 8) cases. We differentiate between (i) ubiquilin 2 aggregation together with phosphorylated TDP-43 or dipeptide repeat proteins; and (ii) ubiquilin 2 self-aggregation promoted by UBQLN2 pathogenic variants that cause amyotrophic lateral sclerosis and/or frontotemporal dementia. Overall, we describe a hippocampal protein aggregation signature that fully distinguishes mutant from wild-type ubiquilin 2 in amyotrophic lateral sclerosis with or without frontotemporal dementia, whereby mutant ubiquilin 2 is more prone than wild-type to aggregate independently of driving factors. This neuropathological signature can be used to assess the pathogenicity of UBQLN2 gene variants and to understand the mechanisms of UBQLN2-linked disease.}, } @article {pmid38702287, year = {2024}, author = {Tazir, M and Nouioua, S}, title = {Distal hereditary motor neuropathies.}, journal = {Revue neurologique}, volume = {180}, number = {10}, pages = {1031-1036}, doi = {10.1016/j.neurol.2023.09.005}, pmid = {38702287}, issn = {0035-3787}, mesh = {Humans ; *Hereditary Sensory and Motor Neuropathy/genetics/diagnosis/physiopathology ; Mutation ; Charcot-Marie-Tooth Disease/genetics/diagnosis/physiopathology/epidemiology ; }, abstract = {Distal hereditary motor neuropathies (dHMN) are a group of heterogeneous hereditary disorders characterized by a slowly progressive distal pure motor neuropathy. Electrophysiology, with normal motor and sensory conduction velocities, can suggest the diagnosis of dHMN and guide the genetic study. More than thirty genes are currently associated with HMNs, but around 60 to 70% of cases of dHMN remain uncharacterized genetically. Recent cohort studies showed that HSPB1, GARS, BICB2 and DNAJB2 are among the most frequent dHMN genes and that the prevalence of the disease was calculated as 2.14 and 2.3 per 100,000. The determination of the different genes involved in dHMNs made it possible to observe a genotypic overlap with some other neurogenetic disorders and other hereditary neuropathies such as CMT2, mainly with the HSPB1, HSPB8, BICD2 and TRPV4 genes of AD-inherited transmission and recently observed with SORD gene of AR transmission which seems relatively frequent and potentially curable. Distal hereditary motor neuropathy that predominates in the upper limbs is linked mainly to three genes: GARS, BSCL2 and REEP1, whereas dHMN with vocal cord palsy is associated with SLC5A7, DCTN1 and TRPV4 genes. Among the rare AR forms of dHMN like IGHMBP2 and DNAJB2, the SIGMAR1 gene mutations as well as VRK1 variants are associated with a motor neuropathy phenotype often associated with upper motoneuron involvement. The differential diagnosis of these latter arises with juvenile forms of amyotrophic lateral sclerosis, that could be caused also by variations of these genes, as well as hereditary spastic paraplegia. A differential diagnosis of dHMN related to Brown Vialetto Van Laere syndrome due to riboflavin transporter deficiency is important to consider because of the therapeutic possibility.}, } @article {pmid38700207, year = {2024}, author = {Keeley, O and Coyne, AN}, title = {Nuclear and degradative functions of the ESCRT-III pathway: implications for neurodegenerative disease.}, journal = {Nucleus (Austin, Tex.)}, volume = {15}, number = {1}, pages = {2349085}, pmid = {38700207}, issn = {1949-1042}, support = {R00 NS123242/NS/NINDS NIH HHS/United States ; R01 NS132836/NS/NINDS NIH HHS/United States ; }, mesh = {Humans ; *Endosomal Sorting Complexes Required for Transport/metabolism ; *Neurodegenerative Diseases/metabolism/pathology/genetics ; Animals ; Cell Nucleus/metabolism ; Frontotemporal Dementia/metabolism/pathology/genetics ; Endosomes/metabolism ; }, abstract = {The ESCRT machinery plays a pivotal role in membrane-remodeling events across multiple cellular processes including nuclear envelope repair and reformation, nuclear pore complex surveillance, endolysosomal trafficking, and neuronal pruning. Alterations in ESCRT-III functionality have been associated with neurodegenerative diseases including Frontotemporal Dementia (FTD), Amyotrophic Lateral Sclerosis (ALS), and Alzheimer's Disease (AD). In addition, mutations in specific ESCRT-III proteins have been identified in FTD/ALS. Thus, understanding how disruptions in the fundamental functions of this pathway and its individual protein components in the human central nervous system (CNS) may offer valuable insights into mechanisms underlying neurodegenerative disease pathogenesis and identification of potential therapeutic targets. In this review, we discuss ESCRT components, dynamics, and functions, with a focus on the ESCRT-III pathway. In addition, we explore the implications of altered ESCRT-III function for neurodegeneration with a primary emphasis on nuclear surveillance and endolysosomal trafficking within the CNS.}, } @article {pmid38697975, year = {2024}, author = {Tsitkov, S and Valentine, K and Kozareva, V and Donde, A and Frank, A and Lei, S and , and E Van Eyk, J and Finkbeiner, S and Rothstein, JD and Thompson, LM and Sareen, D and Svendsen, CN and Fraenkel, E}, title = {Disease related changes in ATAC-seq of iPSC-derived motor neuron lines from ALS patients and controls.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {3606}, pmid = {38697975}, issn = {2041-1723}, support = {RF1 AG057331/AG/NIA NIH HHS/United States ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/pathology/metabolism ; *Induced Pluripotent Stem Cells/metabolism ; *Motor Neurons/metabolism/pathology ; Male ; Female ; Middle Aged ; Case-Control Studies ; Chromatin/metabolism/genetics ; Aged ; Epigenomics/methods ; Chromatin Immunoprecipitation Sequencing/methods ; Disease Progression ; Epigenesis, Genetic ; }, abstract = {Amyotrophic Lateral Sclerosis (ALS), like many other neurodegenerative diseases, is highly heritable, but with only a small fraction of cases explained by monogenic disease alleles. To better understand sporadic ALS, we report epigenomic profiles, as measured by ATAC-seq, of motor neuron cultures derived from a diverse group of 380 ALS patients and 80 healthy controls. We find that chromatin accessibility is heavily influenced by sex, the iPSC cell type of origin, ancestry, and the inherent variance arising from sequencing. Once these covariates are corrected for, we are able to identify ALS-specific signals in the data. Additionally, we find that the ATAC-seq data is able to predict ALS disease progression rates with similar accuracy to methods based on biomarkers and clinical status. These results suggest that iPSC-derived motor neurons recapitulate important disease-relevant epigenomic changes.}, } @article {pmid38697285, year = {2024}, author = {Tuerxun, K and Tang, RH and Abudoumijiti, A and Yusupu, Z and Aikebaier, A and Mijiti, S and Ibrahim, I and Cao, YL and Yasheng, A and Wu, YQ}, title = {Comparative proteomics analysis of samples from hepatic cystic echinococcosis patients using data-independent acquisition approach.}, journal = {Journal of proteomics}, volume = {301}, number = {}, pages = {105191}, doi = {10.1016/j.jprot.2024.105191}, pmid = {38697285}, issn = {1876-7737}, mesh = {*Proteomics/methods ; Humans ; *Echinococcus granulosus/metabolism ; Animals ; Helminth Proteins/metabolism/analysis ; Echinococcosis, Hepatic/metabolism/parasitology ; Proteome/analysis/metabolism ; }, abstract = {Cystic echinococcosis is a zoonotic disease resulting from infection caused by the larval stage of Echinococcus granulosus. This study aimed to assess the specific proteins that are potential candidates for the development of a vaccine against E. granulosus. The data-independent acquisition approach was employed to identify differentially expressed proteins (DEPs) in E. granulosus samples. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was employed to identify several noteworthy proteins. Results: The DEPs in E. granulosus samples were identified (245 pericystic wall vs. parasite-free yellowish granuloma (PYG, 1725 PY vs. PYG, 2274 PN vs. PYG). Further examination of these distinct proteins revealed their predominant enrichment in metabolic pathways, amyotrophic lateral sclerosis, and neurodegeneration-associated pathways. Notably, among these DEPs, SH3BGRL, MST1, TAGLN2, FABP5, UBE2V2, and RARRES2 exhibited significantly higher expression levels in the PYG group compared with the PY group (P < 0.05). The findings may contribute to the understanding of the pathological mechanisms underlying echinococcosis, providing valuable insights into the development of more effective diagnostic tools, treatment modalities, and preventive strategies. SIGNIFICANCE: CE is a major public health hazard in the western regions of China, Central Asia, South America, the Mediterranean countries, and eastern Africa. Echinococcus granulosus is responsible for zoonotic disease through infection Our analysis focuses on the proteins in various samples by data-dependent acquisition (DIA) for proteomic analysis. The importance of this research is to develop new strategies and targets to protect against E. granulosus infections in humans.}, } @article {pmid38697002, year = {2024}, author = {Su, T and Gan, Y and Ma, S and Wu, H and Lu, S and Zhi, M and Wang, B and Lu, Y and Yao, J}, title = {Graves' disease and the risk of five autoimmune diseases: A Mendelian randomization and colocalization study.}, journal = {Diabetes & metabolic syndrome}, volume = {18}, number = {5}, pages = {103023}, doi = {10.1016/j.dsx.2024.103023}, pmid = {38697002}, issn = {1878-0334}, mesh = {Humans ; *Graves Disease/genetics/epidemiology ; *Mendelian Randomization Analysis ; *Autoimmune Diseases/genetics/epidemiology ; Genetic Predisposition to Disease ; Polymorphism, Single Nucleotide ; Prognosis ; Risk Factors ; Crohn Disease/genetics/epidemiology ; Follow-Up Studies ; Lupus Erythematosus, Systemic/genetics/epidemiology ; Arthritis, Rheumatoid/genetics/epidemiology ; }, abstract = {BACKGROUND: Epidemiological studies have consistently demonstrated a high prevalence of concurrent autoimmune diseases in individuals with Graves' disease (GD).

OBJECTIVE: The objective of this study is to establish a causal association between GD and autoimmune diseases.

METHODS: We employed a two-sample Mendelian randomization (MR) to infer a causal association between GD and five autoimmune diseases, namely rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Crohn's disease (CD), ulcerative colitis (UC), and amyotrophic lateral sclerosis (ALS), in the East Asian and European population. Genetic correlations were explored through linkage disequilibrium score regression analysis (LDSC). Finally, colocalization analyses were performed to investigate possible genetic foundations.

RESULTS: Bidirectional MR analysis indicated that genetically predicted GD increased the risk of RA (Odds Ratio (OR): 1.34, 95 % Confidence Interval (CI): 1.21 to 1.47, P < 0.001) and SLE (OR: 1.21, 95%CI: 1.08 to 1.35, P < 0.001) in the East Asian population. In contrast, we found that genetically predicted RA (OR: 1.14, 95%CI: 1.05 to 1.24, P = 0.002) and SLE (OR: 1.10, 95%CI: 1.03 to 1.17, P = 0.003) were associated with a higher risk of GD. The results have been partially validated in European cohorts. Colocalization analysis suggested the potential existence of shared causal variants between GD and other autoimmune diseases. In particular, gene ARID5B may play an important role in the incidence of autoimmune diseases.

CONCLUSION: This study has confirmed that GD was associated with RA and SLE and found a possible key gene ARID5B. It may be necessary to strengthen detection to prevent the occurrence of comorbidities in clinical practice.}, } @article {pmid38696744, year = {2024}, author = {}, title = {Variation in Resting Metabolic Rate Affects Identification of Metabolic Change in Geographically Distinct Cohorts of Patients With ALS.}, journal = {Neurology}, volume = {102}, number = {10}, pages = {e209407}, doi = {10.1212/WNL.0000000000209407}, pmid = {38696744}, issn = {1526-632X}, } @article {pmid38696153, year = {2024}, author = {Chugunov, DA and Shmilovich, AA and Larina, MR and Goncharenko, SN and Moiseeva, TV and Ryauzova, ES and Fedorova, EV and Bukinich, AA}, title = {[Clinical and psychometric characteristics of cognitive and negative disorders in schizophrenia].}, journal = {Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova}, volume = {124}, number = {4. Vyp. 2}, pages = {64-71}, doi = {10.17116/jnevro202412404264}, pmid = {38696153}, issn = {1997-7298}, mesh = {Humans ; Male ; Female ; Adult ; *Schizophrenia/diagnosis/complications ; *Psychometrics ; Middle Aged ; *Schizophrenic Psychology ; Cognition ; Neuropsychological Tests ; Cognition Disorders/diagnosis/etiology ; }, abstract = {OBJECTIVE: To establish the characteristics of clinical manifestations and cognitive tests in patients with schizophrenia, with a predominance of cognitive and negative disorders.

MATERIAL AND METHODS: We examined 76 patients, 66 in the main group, 10 in the comparison group, who were treated in Psychiatric Hospital No. 1 and Psychiatric Hospital No. 4 (Moscow). Clinical-psychopathological, psychometric and statistical methods were used. Features of cognitive functioning were studied using the Frontal Assessment Battery (FAB) and the Edinburgh Cognitive and Behavioural Amyotrophic Lateral Sclerosis (ALS) Screen (ECAS). Emotional intelligence scores were assessed using the Ekman Face Emotion Recognition (EFER) test.

RESULTS: Patients with schizophrenia showed dominance of one of 3 types of deficit symptoms: cognitive, emotional, and volitional. Cognitive functions were significantly reduced in patients with schizophrenia when compared with the comparison group (mean FAB score (M±SD) 13.44±2.97 in patients with schizophrenia vs. 16.10±1.70 in the comparison group; t=4.10; p<0.001). Cognitive functions were particularly reduced in patients with volitional deficit (mean EFER total score 42.40±9.0 in patients with volitional deficit vs. 47.21±633 in patients with cognitive deficit; t=2.12; p=0.039; mean FAB score 12.83±3.29 in patients with volitional deficit vs. 16.10±1.70 in the comparison group; t=4.24; p<0.001; mean ECAS score specific to ALS 78.80±9.07 in patients with volitional deficit vs. 84.50±6.71 in the comparison group; t=2.18; p=0.034).

CONCLUSION: The greatest contribution to the development of cognitive disorders in schizophrenia is made by dysfunction of frontal (especially) and temporal cortex. Executive functions, speech skills and verbal fluency are most severely damaged.}, } @article {pmid38695966, year = {2024}, author = {Mendes Ferreira, V and Caetano, A and Santos, L and Fernandes, M}, title = {FIG4-associated disease manifesting as rapidly progressive amyotrophic lateral sclerosis.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {45}, number = {9}, pages = {4609-4610}, pmid = {38695966}, issn = {1590-3478}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis ; Disease Progression ; Flavoproteins/genetics ; Male ; Middle Aged ; Female ; Phosphoric Monoester Hydrolases ; }, } @article {pmid38695638, year = {2024}, author = {Fullam, T and Hunt, SL and Han, M and Denesia, J and Chandrashekhar, S and Jawdat, O and Piccione, E and Fernandes, JA and Statland, J}, title = {Outcomes after intervention for enteral nutrition in patients with amyotrophic lateral sclerosis in multidisciplinary clinics.}, journal = {Muscle & nerve}, volume = {70}, number = {1}, pages = {94-100}, pmid = {38695638}, issn = {1097-4598}, support = {UL1 TR002366/TR/NCATS NIH HHS/United States ; 10.13039/100000002/NH/NIH HHS/United States ; 10.13039/100000002/NH/NIH HHS/United States ; 10.13039/100005202//Muscular Dystrophy Association/ ; //FSHD Society/ ; //Friends of FSH Research/ ; //and FSHD Canada/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy/complications ; Male ; Female ; *Enteral Nutrition/methods ; Aged ; Retrospective Studies ; Middle Aged ; *Gastrostomy ; Treatment Outcome ; Malnutrition/etiology/therapy ; Vital Capacity/physiology ; }, abstract = {INTRODUCTION/AIMS: Patients with amyotrophic lateral sclerosis (ALS) are susceptible to malnutrition, with appropriate management of nutritional interventions an active area of investigation. We sought to determine the impact of gastrostomy tube placement in ALS patients, exploring the correlation between forced vital capacity (FVC), malnutrition, and perioperative complications.

METHODS: A retrospective review was performed of clinically diagnosed ALS patients treated at two multidisciplinary clinics (University of Kansas, University of Nebraska) from January 2009 to September 2020 who were referred for gastrostomy. Data collected included demographics, disease characteristics, and key gastrostomy related dates/outcomes.

RESULTS: Two hundred thirty-nine patients were included with a median age of 65 years and median of 589 days from symptom onset to gastrostomy (interquartile range, 404-943). The population was predominantly Non-Hispanic White with bulbar-onset ALS. 30-day mortality was 4% and 30-day morbidity was 13%. Weight loss, body mass index, and predicted FVC at placement showed no increased 30-day morbidity or mortality association. Bulbar-onset ALS patients exhibited higher overall mortality postplacement than limb onset (odds ratio: 1.85, 95% confidence interval: 1.03-3.33). There was a 5% incidence of symptoms suggestive of refeeding syndrome.

DISCUSSION: Rates of major/minor complications and 30-day mortality related to gastrostomy placement in our population were similar compared with prior studies in ALS. The lack of difference in outcomes based on FVC at procedure may suggest this is not predictive of outcome, or perhaps, high-quality perioperative respiratory management. Alternative reasons may account for the increased morbidity and mortality of gastrostomy placement in the ALS population.}, } @article {pmid38694387, year = {2024}, author = {Arora, H and Javed, B and Kutikuppala, LVS and Chaurasia, M and Khullar, K and Kannan, S and Golla, V}, title = {ST2 levels and neurodegenerative diseases: is this a significant relation?.}, journal = {Annals of medicine and surgery (2012)}, volume = {86}, number = {5}, pages = {2812-2817}, pmid = {38694387}, issn = {2049-0801}, abstract = {Interleukin-33 (IL-33), belonging to the interleukin-1 cytokine family, has a decoy receptor soluble ST2 (sST2). IL-33 is found in oligodendrocytes and astrocytes and is involved in central nervous system healing and repair, whereas ST2 is found in microglia and astrocytes. Some studies have found a link between changes in the IL-33/ST2 pathway and neurodegenerative disorders. This review article investigates the relationship between the interleukin-33 (IL-33)/ST2 pathway and neurodegenerative disorders. It was discovered that soluble st2 levels were increased. Furthermore, IL-33 levels were found to be lower in many neurodegenerative diseases such as Alzheimer's and amyotrophic lateral sclerosis (ALS). The association with other disorders, such as ankylosing spondylitis, multiple sclerosis, and systemic lupus erythematosus (SLE), was also observed. Various studies suggest that ST2/IL-33 signalling may be pivotal in the disease modulation of neurodegenerative disorders. The serum sST2 level test can be useful in determining the inflammatory status and severity of illness in many neurodegenerative disorders. In this review, we will discuss recent findings concerning the interleukin-33 (IL-33)/ST2 pathway and its role in the diagnosis and treatment of diseases with neurodegeneration.}, } @article {pmid38694349, year = {2024}, author = {Amjadi, N and Mohammadi, S and Paybast, S and Dadkhah, P and Talayeh, M and Asemi, Z}, title = {A pregnant woman with amyotrophic lateral sclerosis from Iran: a case report.}, journal = {Annals of medicine and surgery (2012)}, volume = {86}, number = {5}, pages = {3013-3015}, pmid = {38694349}, issn = {2049-0801}, abstract = {INTRODUCTION AND IMPORTANCE: Amyotrophic lateral sclerosis (ALS) is a progressive motor neuron disease, which is extremely rare during pregnancy. The severity of the disease affects the pregnancy outcome. The present study reports the first Iranian case of a woman with ALS overlapping pregnancy.

CASE PRESENTATION: The 27-year-old lady in her second pregnancy was admitted to the emergency department with labor pain at the 37th gestation week. Following a multidisciplinary team meeting, including a neurologist, maternal-fetal medicine specialist, and anesthesiologist, a decision was made for an emergent cesarean section under spinal anesthesia. The delivery was successful without any maternal or fetal complications. A 5-month follow-up revealed the stable neurologic status of the mother.

CLINICAL DISCUSSION: The combination of ALS and pregnancy is very rare because the disease is more common in elderly men. ALS management involves a multidisciplinary approach. Riluzole is a drug that can increase the survival of the patients. ALS does not affect on motor and sensory nerves of the uterus, so vaginal delivery might be possible. The main cause of cesarean section in patients with ALS is respiratory compromise, but four patients with uncomplicated vaginal deliveries have been reported. The neonatal outcome of most cases resulted in normal healthy infants.

CONCLUSION: Management of ALS in pregnancy is challenging because of respiratory concerns, so multidisciplinary team management is important.}, } @article {pmid38692734, year = {2024}, author = {van Tartwijk, FW and Wunderlich, LCS and Mela, I and Makarchuk, S and Jakobs, MAH and Qamar, S and Franze, K and Kaminski Schierle, GS and St George-Hyslop, PH and Lin, JQ and Holt, CE and Kaminski, CF}, title = {Mutation of the ALS-/FTD-Associated RNA-Binding Protein FUS Affects Axonal Development.}, journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, volume = {44}, number = {27}, pages = {}, pmid = {38692734}, issn = {1529-2401}, support = {772426/ERC_/European Research Council/International ; MR/K015850/1/MRC_/Medical Research Council/United Kingdom ; 109145/WT_/Wellcome Trust/United Kingdom ; MR/K02292X/1/MRC_/Medical Research Council/United Kingdom ; 215943/WT_/Wellcome Trust/United Kingdom ; }, mesh = {*RNA-Binding Protein FUS/genetics/metabolism ; *Axons/pathology/metabolism ; Animals ; *Amyotrophic Lateral Sclerosis/genetics/pathology/metabolism ; *Frontotemporal Dementia/genetics/pathology/metabolism ; *Mutation ; Female ; Male ; Xenopus laevis ; Growth Cones/metabolism ; Humans ; Disease Models, Animal ; }, abstract = {Aberrant condensation and localization of the RNA-binding protein (RBP) fused in sarcoma (FUS) occur in variants of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Changes in RBP function are commonly associated with changes in axonal cytoskeletal organization and branching in neurodevelopmental disorders. Here, we asked whether branching defects also occur in vivo in a model of FUS-associated disease. We use two reported Xenopus models of ALS/FTD (of either sex), the ALS-associated mutant FUS(P525L) and a mimic of hypomethylated FUS, FUS(16R). Both mutants strongly reduced axonal complexity in vivo. We also observed an axon looping defect for FUS(P525L) in the target area, which presumably arises due to errors in stop cue signaling. To assess whether the loss of axon complexity also had a cue-independent component, we assessed axonal cytoskeletal integrity in vitro. Using a novel combination of fluorescence and atomic force microscopy, we found that mutant FUS reduced actin density in the growth cone, altering its mechanical properties. Therefore, FUS mutants may induce defects during early axonal development.}, } @article {pmid38691665, year = {2024}, author = {Singh, P and Belliveau, P and Towle, J and Neculau, AE and Dima, L}, title = {Edaravone Oral Suspension: A Neuroprotective Agent to Treat Amyotrophic Lateral Sclerosis.}, journal = {American journal of therapeutics}, volume = {31}, number = {3}, pages = {e258-e267}, doi = {10.1097/MJT.0000000000001742}, pmid = {38691665}, issn = {1536-3686}, mesh = {*Edaravone/administration & dosage/pharmacology/therapeutic use ; Humans ; *Amyotrophic Lateral Sclerosis/drug therapy ; *Neuroprotective Agents/administration & dosage/therapeutic use/adverse effects ; Administration, Oral ; Suspensions ; Biological Availability ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is characterized by loss of motor neurons due to degeneration of nerve cells within the brain and spinal cord. Early symptoms include limb weakness, twitching or muscle cramping, and slurred speech. As the disease progresses, difficulty breathing, swallowing, and paralysis can lead to death. Currently, there are no medications that cure ALS, and guidelines recommend treatments focused on symptom management. Intravenous (IV) edaravone was approved by the US Food and Drug Administration (FDA) in 2017 as a treatment to slow the progression of ALS. In May 2022, the FDA approved an oral suspension (ORS) formulation of edaravone.

MECHANISM OF ACTION: The mechanism of action of edaravone is not well defined. However, its neuroprotective effects are thought to result from antioxidant properties occurring through elimination of free radicals.

PHARMACOKINETICS: Edaravone ORS (105 mg) has a bioavailability of 57% when compared with edaravone IV (60 mg). The ORS should be taken on an empty stomach in the morning, with water and no food or beverages, for 1 hour. Edaravone is bound to albumin (92%), has a mean volume of distribution of 63.1 L, a half-life of 4.5-9 hours, and a total clearance of 35.9 L/h after intravenous administration. Edaravone is metabolized into nonactive sulfate and glucuronide conjugates.

CLINICAL TRIALS: The FDA approval was based on studies of the pharmacokinetics, safety, tolerability, and bioavailability of edaravone ORS. A phase III, global, multicenter, open-label safety study was conducted on edaravone ORS in 185 patients with ALS over 48 weeks. The most reported treatment-emergent adverse events were falls, muscular weakness, and constipation. Serious treatment-emergent adverse events included disease worsening, dysphagia, dyspnea, and respiratory failure.

THERAPEUTIC ADVANCE: Oral edaravone is an ALS treatment that can be self-administered or administered by a caregiver, precluding the need for administration by a health care professional in an institutional setting.}, } @article {pmid38689650, year = {2024}, author = {Swindell, WR}, title = {Meta-analysis of differential gene expression in lower motor neurons isolated by laser capture microdissection from post-mortem ALS spinal cords.}, journal = {Frontiers in genetics}, volume = {15}, number = {}, pages = {1385114}, pmid = {38689650}, issn = {1664-8021}, abstract = {INTRODUCTION: ALS is a fatal neurodegenerative disease for which underlying mechanisms are incompletely understood. The motor neuron is a central player in ALS pathogenesis but different transcriptome signatures have been derived from bulk analysis of post-mortem tissue and iPSC-derived motor neurons (iPSC-MNs).

METHODS: This study performed a meta-analysis of six gene expression studies (microarray and RNA-seq) in which laser capture microdissection (LCM) was used to isolate lower motor neurons from post-mortem spinal cords of ALS and control (CTL) subjects. Differentially expressed genes (DEGs) with consistent ALS versus CTL expression differences across studies were identified.

RESULTS: The analysis identified 222 ALS-increased DEGs (FDR <0.10, SMD >0.80) and 278 ALS-decreased DEGs (FDR <0.10, SMD < -0.80). ALS-increased DEGs were linked to PI3K-AKT signaling, innate immunity, inflammation, motor neuron differentiation and extracellular matrix. ALS-decreased DEGs were associated with the ubiquitin-proteosome system, microtubules, axon growth, RNA-binding proteins and synaptic membrane. ALS-decreased DEG mRNAs frequently interacted with RNA-binding proteins (e.g., FUS, HuR). The complete set of DEGs (increased and decreased) overlapped significantly with genes near ALS-associated SNP loci (p < 0.01). Transcription factor target motifs with increased proximity to ALS-increased DEGs were identified, most notably DNA elements predicted to interact with forkhead transcription factors (e.g., FOXP1) and motor neuron and pancreas homeobox 1 (MNX1). Some of these DNA elements overlie ALS-associated SNPs within known enhancers and are predicted to have genotype-dependent MNX1 interactions. DEGs were compared to those identified from SOD1-G93A mice and bulk spinal cord segments or iPSC-MNs from ALS patients. There was good correspondence with transcriptome changes from SOD1-G93A mice (r ≤ 0.408) but most DEGs were not differentially expressed in bulk spinal cords or iPSC-MNs and transcriptome-wide effect size correlations were weak (bulk tissue: r ≤ 0.207, iPSC-MN: r ≤ 0.037).

CONCLUSION: This study defines a robust transcriptome signature from LCM-based motor neuron studies of post-mortem tissue from ALS and CTL subjects. This signature differs from those obtained from analysis of bulk spinal cord segments and iPSC-MNs. Results provide insight into mechanisms underlying gene dysregulation in ALS and highlight connections between these mechanisms, ALS genetics, and motor neuron biology.}, } @article {pmid38689506, year = {2024}, author = {Parvizi, T and Klotz, S and Keritam, O and Caliskan, H and Imhof, S and König, T and Haider, L and Traub-Weidinger, T and Wagner, M and Brunet, T and Brugger, M and Zimprich, A and Rath, J and Stögmann, E and Gelpi, E and Cetin, H}, title = {Clinical heterogeneity within the ALS-FTD spectrum in a family with a homozygous optineurin mutation.}, journal = {Annals of clinical and translational neurology}, volume = {11}, number = {6}, pages = {1579-1589}, pmid = {38689506}, issn = {2328-9503}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/pathology/physiopathology/diagnosis ; *Membrane Transport Proteins/genetics ; *Cell Cycle Proteins/genetics ; *Frontotemporal Dementia/genetics/pathology/physiopathology ; Male ; Adult ; Female ; Pedigree ; Transcription Factor TFIIIA/genetics ; Siblings ; Frameshift Mutation ; Homozygote ; }, abstract = {OBJECTIVE: Mutations in the gene encoding for optineurin (OPTN) have been reported in the context of different neurodegenerative diseases including the amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) spectrum. Based on single case reports, neuropathological data in OPTN mutation carriers have revealed transactive response DNA-binding protein 43 kDa (TDP-43) pathology, in addition to accumulations of tau and alpha-synuclein. Herein, we present two siblings from a consanguineous family with a homozygous frameshift mutation in the OPTN gene and different clinical presentations.

METHODS: Both affected siblings underwent (i) clinical, (ii) neurophysiological, (iii) neuropsychological, (iv) radiological, and (v) laboratory examinations, and (vi) whole-exome sequencing (WES). Postmortem histopathological examination was conducted in the index patient, who deceased at the age of 41.

RESULTS: The index patient developed rapidly progressing clinical features of upper and lower motor neuron dysfunction as well as apathy and cognitive deterioration at the age of 41. Autopsy revealed an ALS-FTLD pattern associated with prominent neuronal and oligodendroglial TDP-43 pathology, and an atypical limbic 4-repeat tau pathology reminiscent of argyrophilic grain disease. The brother of the index patient exhibited behavioral changes and mnestic deficits at the age of 38 and was diagnosed with behavioral FTD 5 years later, without any evidence of motor neuron dysfunction. WES revealed a homozygous frameshift mutation in the OPTN gene in both siblings (NM_001008212.2: c.1078_1079del; p.Lys360ValfsTer18).

INTERPRETATION: OPTN mutations can be associated with extensive TDP-43 pathology and limbic-predominant tauopathy and present with a heterogeneous clinical phenotype within the ALS-FTD spectrum within the same family.}, } @article {pmid38687737, year = {2024}, author = {Lumi, R and Petri, S and Siwy, J and Latosinska, A and Raad, J and Zürbig, P and Skripuletz, T and Mischak, H and Beige, J}, title = {Small peptide CSF fingerprint of amyotrophic lateral sclerosis.}, journal = {PloS one}, volume = {19}, number = {4}, pages = {e0302280}, pmid = {38687737}, issn = {1932-6203}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/cerebrospinal fluid ; Female ; Male ; Middle Aged ; Aged ; *Peptides/cerebrospinal fluid ; Proteomics/methods ; Adult ; Biomarkers/cerebrospinal fluid ; Case-Control Studies ; Tandem Mass Spectrometry ; Chromatography, Liquid ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by abnormal protein aggregation in the motor neurons. Present and earlier proteomic studies to characterize peptides in cerebrospinal fluid (CSF) associated with motoneuron pathology did not target low molecular weight proteins and peptides. We hypothesized that specific changes in CSF peptides or low molecular weight proteins are significantly altered in ALS, and that these changes may support deciphering molecular pathophysiology and even guide approaches towards therapeutic interventions.

METHODS: Cerebrospinal fluid (CSF) from 50 ALS patients and 50 non-ALS controls was collected, centrifuged immediately after collection, aliquoted into polypropylene test tubes, frozen within 30-40 min after the puncture, and stored at -80°C until use. Peptides were sequenced using capillary electrophoresis or liquid chromatography/mass spectrometry (CE-MS/MS or LC-MS/MS).

FINDINGS: In the CSF of 50 patients and 50 non-ALS controls 33 peptides were found, of which 14 could be sequenced using a non-lytic single-pot proteomic detection method, CE/MS. ALS deregulated peptides vs. controls included Integral membrane protein 2B, Neurosecretory protein VGF, Osteopontin, Neuroendocrine protein 7B2 (Secretogranin-V), EGF-containing fibulin-like extracellular matrix protein 1, Xylosyltransferase 1 XT-1, Chromogranin-A, Superoxide dismutase SOD-1, Secretogranin-1 (Chromogranin B), NR2F2 Nuclear Receptor Subfamily 2 Group F Member 2 and Collagen alpha-1(VII) chain.

INTERPRETATION: Most striking deregulations in CSF from ALS patients were found in VGF, Osteopontin, SOD-1 and EFEMP1 peptides. No associations of disease severity, duration and region of onset with sequenced peptides were found.}, } @article {pmid38686337, year = {2024}, author = {Felix, C and Johnston, JD and Owen, K and Shirima, E and Hinds, SR and Mandl, KD and Milinovich, A and Alberts, JL}, title = {Explainable machine learning for predicting conversion to neurological disease: Results from 52,939 medical records.}, journal = {Digital health}, volume = {10}, number = {}, pages = {20552076241249286}, pmid = {38686337}, issn = {2055-2076}, abstract = {OBJECTIVE: This study assesses the application of interpretable machine learning modeling using electronic medical record data for the prediction of conversion to neurological disease.

METHODS: A retrospective dataset of Cleveland Clinic patients diagnosed with Alzheimer's disease, amyotrophic lateral sclerosis, multiple sclerosis, or Parkinson's disease, and matched controls based on age, sex, race, and ethnicity was compiled. Individualized risk prediction models were created using eXtreme Gradient Boosting for each neurological disease at four timepoints in patient history. The prediction models were assessed for transparency and fairness.

RESULTS: At timepoints 0-months, 12-months, 24-months, and 60-months prior to diagnosis, Alzheimer's disease models achieved the area under the receiver operating characteristic curve on a holdout test dataset of 0.794, 0.742, 0.709, and 0.645; amyotrophic lateral sclerosis of 0.883, 0.710, 0.658, and 0.620; multiple sclerosis of 0.922, 0.877, 0.849, and 0.781; and Parkinson's disease of 0.809, 0.738, 0.700, and 0.651, respectively.

CONCLUSIONS: The results demonstrate that electronic medical records contain latent information that can be used for risk stratification for neurological disorders. In particular, patient-reported outcomes, sleep assessments, falls data, additional disease diagnoses, and longitudinal changes in patient health, such as weight change, are important predictors.}, } @article {pmid38685454, year = {2024}, author = {Gadri, Y and Avneri, A and Peleg, Z}, title = {Induced mutation in the SiALS gene offers new weed management opportunities for sesame crop.}, journal = {Plant science : an international journal of experimental plant biology}, volume = {345}, number = {}, pages = {112104}, doi = {10.1016/j.plantsci.2024.112104}, pmid = {38685454}, issn = {1873-2259}, mesh = {*Weed Control/methods ; *Herbicide Resistance/genetics ; *Sesamum/genetics/growth & development ; *Herbicides/pharmacology ; Acetolactate Synthase/genetics ; Plant Weeds/genetics/drug effects ; Plant Proteins/genetics/metabolism ; Mutation ; Crops, Agricultural/genetics/growth & development ; }, abstract = {Weeds are the primary biotic constraint affecting sesame growth and production. Here, we applied EMS mutagenesis to an elite sesame cultivar and discovered a novel point mutation in the sesame SiALS gene conferring resistance to imidazolinone, a group of acetolactate-synthase (ALS)-inhibitors. The mutant line exhibited high resistance to imazamox, an ALS-inhibitor, with hybrid plants displaying an intermediate response. Field-based validation confirmed the mutant line's substantial resistance, leading to a significantly higher yield under imazamox treatment. Under pre-emergence application of imazapic, the mutant plants sustained growth, whereas wild-type and weed were effectively controlled. Field trials using s-metolachlor and imazapic combined resulted in weed-free plots compared to untreated controls. Consequently, this treatment showed a significantly greater yield (2280 vs. 880 Kg ha[-1]) than the commercial practice (s-metolachlor). Overall, our study unveils the potential of utilizing this point mutation in sesame breeding programs, offering new opportunities for integrated weed management strategies for sesame cultivation. Developing herbicide-resistant crop plants holds promise for supporting sustainable production and addressing the challenges of weed infestations in sesame farming.}, } @article {pmid38685248, year = {2024}, author = {Chtourou, M and Osuna, MD and Vázquez-García, JG and Lozano-Juste, J and De Prado, R and Torra, J and Souissi, T}, title = {Pro197Ser and the new Trp574Leu mutations together with enhanced metabolism contribute to cross-resistance to ALS inhibiting herbicides in Sinapis alba.}, journal = {Pesticide biochemistry and physiology}, volume = {201}, number = {}, pages = {105882}, doi = {10.1016/j.pestbp.2024.105882}, pmid = {38685248}, issn = {1095-9939}, mesh = {*Acetolactate Synthase/genetics/metabolism/antagonists & inhibitors ; *Herbicides/pharmacology ; *Herbicide Resistance/genetics ; *Sinapis/drug effects/genetics ; *Malathion/pharmacology ; *Mutation ; Plant Proteins/genetics/metabolism ; Arylsulfonates/pharmacology ; Molecular Docking Simulation ; Imidazoles/pharmacology ; }, abstract = {White mustard, (Sinapis alba), a problematic broadleaf weed in many Mediterranean countries in arable fields has been detected as resistant to tribenuron-methyl in Tunisia. Greenhouse and laboratory studies were conducted to characterize Target-Site Resistance (TSR) and the Non-Target Site Resistance (NTSR) mechanisms in two suspected white mustard biotypes. Herbicide dose-response experiments confirmed that the two S. alba biotypes were resistant to four dissimilar acetolactate synthase (ALS)-pinhibiting herbicide chemistries indicating the presence of cross-resistance mechanisms. The highest resistance factor (>144) was attributed to tribenuron-methyl herbicide and both R populations survived up to 64-fold the recommended field dose (18.7 g ai ha[-1]). In this study, the metabolism experiments with malathion (a cytochrome P450 inhibitor) showed that malathion reduced resistance to tribenuron-methyl and imazamox in both populations, indicating that P450 may be involved in the resistance. Sequence analysis of the ALS gene detected target site mutations in the two R biotypes, with amino acid substitutions Trp574Leu, the first report for the species, and Pro197Ser. Molecular docking analysis showed that ALS[Pro197Ser] enzyme cannot properly bind to tribenuron-methyl's aromatic ring due to a reduction in the number of hydrogen bonds, while imazamox can still bind. However, Trp574Leu can weaken the binding affinity between the mutated ALS enzyme and both herbicides with the loss of crucial interactions. This investigation provides substantial evidence for the risk of evolving multiple resistance in S. alba to auxin herbicides while deciphering the TSR and NTSR mechanisms conferring cross resistance to ALS inhibitors.}, } @article {pmid38685231, year = {2024}, author = {Deng, W and Yao, S and Li, Y and Yin, H and Yang, Q and Yuan, S}, title = {An Asp376Glu substitution and P450s-involved metabolism endow resistance to ALS inhibitors in an Ammannia auriculata Willd. Population.}, journal = {Pesticide biochemistry and physiology}, volume = {201}, number = {}, pages = {105911}, doi = {10.1016/j.pestbp.2024.105911}, pmid = {38685231}, issn = {1095-9939}, mesh = {*Acetolactate Synthase/genetics/antagonists & inhibitors ; *Herbicides/pharmacology ; *Herbicide Resistance/genetics ; *Cytochrome P-450 Enzyme System/genetics/metabolism ; Malathion/pharmacology ; Sulfonylurea Compounds/pharmacology ; Plant Weeds/drug effects/genetics ; Amino Acid Substitution ; }, abstract = {Ammannia auriculata Willd. is a noxious broadleaf weed, commonly infesting rice ecosystems across southern China. A putative resistant A. auriculata population (AHSC-5) was sampled from a rice field of Anhui Province, where bensulfuron-methyl (BM) was unable to control its occurrence. This study aimed to determine the sensitivities of the AHSC-5 population to common-use herbicides, and to investigate the underlying resistance mechanisms. The bioassays showed that the AHSC-5 population was 138.1-fold resistant to BM, compared with the susceptible population (JSGL-1). Pretreatment of malathion reduced the resistance index to 19.5. ALS sequencing revealed an Asp376Glu substitution in the AHSC-5 population, and in vitro ALS activity assays found that 50% activity inhibition (I50) of BM in AHSC-5 was 75.4 times higher than that of JSGL-1. Moreover, the AHSC-5 population displayed cross-resistance to pyrazosulfuron-ethyl (10.6-fold), bispyribac‑sodium (3.6-fold), and imazethapyr (2.2-fold), and was in the process of evolving multiple resistance to synthetic auxin herbicides fluroxypyr (2.3-fold) and florpyrauxifen-benzyl (3.1-fold). This study proved the BM resistance in A. auriculata caused by the Asp376Glu mutation and P450-regulated metabolism. This multi-resistant population can still be controlled by penoxsulam, MCPA, bentazone, and carfentrazone-ethyl, which aids in developing targeted and effective weed management strategies.}, } @article {pmid38684907, year = {2024}, author = {Nelson, AT and Cicardi, ME and Markandaiah, SS and Han, JY and Philp, NJ and Welebob, E and Haeusler, AR and Pasinelli, P and Manfredi, G and Kawamata, H and Trotti, D}, title = {Glucose hypometabolism prompts RAN translation and exacerbates C9orf72-related ALS/FTD phenotypes.}, journal = {EMBO reports}, volume = {25}, number = {5}, pages = {2479-2510}, pmid = {38684907}, issn = {1469-3178}, support = {RF1 NS114128/NS/NINDS NIH HHS/United States ; W81XWH-21-1-0134//DOD | USA | MEDCOM | MRDC | U.S. Army Medical Research Acquisition Activity (USAMRAA)/ ; F31-NS118838//HHS | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; R01 NS109150/NS/NINDS NIH HHS/United States ; RF1-NS114128//HHS | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; 628389//Muscular Dystrophy Association (MDA)/ ; R35 NS122209/NS/NINDS NIH HHS/United States ; R21 NS090912/NS/NINDS NIH HHS/United States ; RO1-NS109150//HHS | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; F31 NS118838/NS/NINDS NIH HHS/United States ; RF1-AG057882//HHS | NIH | National Institute on Aging (NIA)/ ; RF1 AG057882/AG/NIA NIH HHS/United States ; R21-NS090912//HHS | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; }, mesh = {Animals ; Mice ; Adenosine Triphosphate/metabolism ; *Amyotrophic Lateral Sclerosis/metabolism/genetics/pathology ; Brain/metabolism/pathology ; *C9orf72 Protein/genetics/metabolism ; Disease Models, Animal ; DNA Repeat Expansion/genetics ; *Frontotemporal Dementia/genetics/metabolism/pathology ; *Glucose/metabolism ; Mice, Transgenic ; Neurons/metabolism ; *Phenotype ; Protein Biosynthesis ; *ran GTP-Binding Protein/metabolism ; }, abstract = {The most prevalent genetic cause of both amyotrophic lateral sclerosis and frontotemporal dementia is a (GGGGCC)n nucleotide repeat expansion (NRE) occurring in the first intron of the C9orf72 gene (C9). Brain glucose hypometabolism is consistently observed in C9-NRE carriers, even at pre-symptomatic stages, but its role in disease pathogenesis is unknown. Here, we show alterations in glucose metabolic pathways and ATP levels in the brains of asymptomatic C9-BAC mice. We find that, through activation of the GCN2 kinase, glucose hypometabolism drives the production of dipeptide repeat proteins (DPRs), impairs the survival of C9 patient-derived neurons, and triggers motor dysfunction in C9-BAC mice. We also show that one of the arginine-rich DPRs (PR) could directly contribute to glucose metabolism and metabolic stress by inhibiting glucose uptake in neurons. Our findings provide a potential mechanistic link between energy imbalances and C9-ALS/FTD pathogenesis and suggest a feedforward loop model with potential opportunities for therapeutic intervention.}, } @article {pmid38683778, year = {2024}, author = {Brennan, MR and Keast, DH and Bain, K and Bain, M and Lorentsen, B and Ayoub, N}, title = {Defining wound bed conformability: a new testing methodology to assess the relative swelling rise of foam dressings.}, journal = {Journal of wound care}, volume = {33}, number = {5}, pages = {312-323}, doi = {10.12968/jowc.2024.33.5.312}, pmid = {38683778}, issn = {0969-0700}, mesh = {Humans ; *Wound Healing ; *Bandages ; Reproducibility of Results ; Exudates and Transudates ; Materials Testing ; Wounds and Injuries/therapy ; }, abstract = {OBJECTIVE: Using a dressing that expands and conforms to the wound bed upon exudate absorption is one of the best ways to promote wound healing. While many products claim wound bed conformability, no externally replicated or verified test methodology had been developed to quantify a wound dressing's ability to conform to the wound bed. The Relative Swelling Rise (RSR) test methodology was developed to measure the relative swelling rise of foam dressings upon fluid absorption, and offers a quantifiable and easily replicated method to measure wound bed conformability.

METHOD: The RSR test method was developed, validated and reliability tested by Coloplast A/S, Denmark. External replication was provided by ALS Odense, Denmark (previously DB Lab). Circular fences provide a fixed diameter to apply and contain the fluid and prevent horizontal spreading in the test set-up. The swelling height is quantified relative to the fence's inner diameter, i.e., the ratio alpha (α), and allows evaluation of a material's ability to conform to the wound bed.

RESULTS: Biatain Silicone foam products (n=3, Coloplast A/S, Denmark) were tested, all afforded an average α-ratio from 0.30 to 0.60. The relative standard deviations were between 1-3%, demonstrating the strength of the test. Robustness of the methodology was demonstrated through the internal validation study, the reliability study, and both an internal and external replication study, as well as a systematic literature review and expert review of the construct, content, criterion and generalisability of the method.

CONCLUSION: Having a validated, effective and easily replicable testing method to quantify wound bed conformability of foam dressings is an important step towards achieving better healing outcomes.}, } @article {pmid38683209, year = {2024}, author = {Wohnrade, C and Seeliger, T and Gingele, S and Bjelica, B and Skripuletz, T and Petri, S}, title = {Diagnostic value of neurofilaments in differentiating motor neuron disease from multifocal motor neuropathy.}, journal = {Journal of neurology}, volume = {271}, number = {7}, pages = {4441-4452}, pmid = {38683209}, issn = {1432-1459}, mesh = {Humans ; *Motor Neuron Disease/diagnosis/blood/cerebrospinal fluid/physiopathology ; Male ; Female ; Middle Aged ; *Neurofilament Proteins/blood/cerebrospinal fluid ; Retrospective Studies ; Diagnosis, Differential ; Aged ; *Biomarkers/blood/cerebrospinal fluid ; *Polyneuropathies/diagnosis/blood/cerebrospinal fluid/physiopathology ; Adult ; }, abstract = {OBJECTIVE: To evaluate the performance of serum neurofilament light chain (NfL) and cerebrospinal fluid (CSF) phosphorylated neurofilament heavy chain (pNfH) as diagnostic biomarkers for the differentiation between motor neuron disease (MND) and multifocal motor neuropathy (MMN).

METHODS: This retrospective, monocentric study included 16 patients with MMN and 34 incident patients with MND. A subgroup of lower motor neuron (MN) dominant MND patients (n = 24) was analyzed separately. Serum NfL was measured using Ella automated immunoassay, and CSF pNfH was measured using enzyme-linked immunosorbent assay. Area under the curve (AUC), optimal cutoff values (Youden's index), and correlations with demographic characteristics were calculated.

RESULTS: Neurofilament concentrations were significantly higher in MND compared to MMN (p < 0.001), and serum NfL and CSF pNfH correlated strongly with each other (Spearman's rho 0.68, p < 0.001). Serum NfL (AUC 0.946, sensitivity and specificity 94%) and CSF pNfH (AUC 0.937, sensitivity 90.0%, specificity 100%) performed excellent in differentiating MND from MMN. Optimal cutoff values were ≥ 44.15 pg/mL (serum NfL) and ≥ 715.5 pg/mL (CSF pNfH), respectively. Similar results were found when restricting the MND cohort to lower MN dominant patients. Only one MMN patient had serum NfL above the cutoff. Two MND patients presented with neurofilament concentrations below the cutoffs, both featuring a slowly progressive disease.

CONCLUSION: Neurofilaments are valuable supportive biomarkers for the differentiation between MND and MMN. Serum NfL and CSF pNfH perform similarly well and elevated neurofilaments in case of diagnostic uncertainty underpin MND diagnosis.}, } @article {pmid38682649, year = {2024}, author = {Zhou, Q and Jiang, X and Zhang, X and Wang, D and Yang, G and Zhou, H and Wu, Y and Guo, F and Chen, M and Diao, G and Ni, L}, title = {Polyoxomolybdate-Based Metal-Organic Framework-Derived Cu-Embedded Molybdenum Dioxide Hybrid Nanoparticles as Highly Efficient Electrocatalysts for Al-S Batteries.}, journal = {ChemSusChem}, volume = {17}, number = {19}, pages = {e202400424}, doi = {10.1002/cssc.202400424}, pmid = {38682649}, issn = {1864-564X}, support = {21971221//National Natural Science Foundation of China/ ; 21401162//National Natural Science Foundation of China/ ; 21773203//National Natural Science Foundation of China/ ; KYCX22_3467//Postgraduate Research & Practice Innovation Program of Jiangsu Province/ ; yzuxk202010//Yangzhou University Interdisciplinary Research Foundation for Chemistry Discipline/ ; //Colleges and Universities of Jiangsu Province/ ; //Lvyangjinfeng Talent Program of Yangzhou/ ; }, abstract = {High-performance rechargeable aluminum-sulfur batteries (RASB) have great potential for various applications owing to their high theoretical capacity, abundant sulfur resources, and good safety. Nevertheless, the practical application of RASB still faces several challenges, including the polysulfide shuttle phenomenon and low sulfur utilization efficiency. Here, we first developed a synergistic copper heterogeneous metal oxide MoO2 derived from polymolybdate-based metal-organic framework as an efficient catalyst for mitigating polysulfide diffusion. This composite enhances sulfur utilization and electrical conductivity of the cathode. DFT calculations and experimental results reveal the catalyst Cu/MoO2@C not only effectively anchors aluminum polysulfides (AlPSs) to mitigate the shuttle effect, but also significantly promotes the catalytic conversion of AlPSs on the sulfur cathode side during charging and discharging. The unique nanostructure contains abundant electrocatalytic active sites of oxide nanoparticles and Cu clusters, resulting in excellent electrochemical performance. Consequently, the established RASB exhibits an initial capacity of 875 mAh g[-1] at 500 mA g[-1] and maintains a capacity of 967 mAh g[-1] even at a high temperature of 50 °C.}, } @article {pmid38682227, year = {2024}, author = {Mohammadi, S and Ghaderi, S and Mohammadi, M and Najafi Asli Pashaki, Z and Khatyal, R and Mohammadian, F and Mohammadjani, S}, title = {Thalamic Alterations in Motor Neuron Diseases: A Systematic Review of MRI Findings.}, journal = {Journal of integrative neuroscience}, volume = {23}, number = {4}, pages = {77}, doi = {10.31083/j.jin2304077}, pmid = {38682227}, issn = {0219-6352}, mesh = {Humans ; *Thalamus/diagnostic imaging/pathology/physiopathology ; *Motor Neuron Disease/diagnostic imaging/pathology/physiopathology ; *Magnetic Resonance Imaging ; Amyotrophic Lateral Sclerosis/diagnostic imaging/pathology/physiopathology ; }, abstract = {BACKGROUND: Motor neuron diseases (MNDs) are progressive neurodegenerative disorders characterized by motor impairment and non-motor symptoms. The involvement of the thalamus in MNDs, especially in conditions such as amyotrophic lateral sclerosis (ALS), and its interaction with frontotemporal dementia (FTD), has garnered increasing research interest. This systematic review analyzed magnetic resonance imaging (MRI) studies that focused on thalamic alterations in MNDs to understand the significance of these changes and their correlation with clinical outcomes.

METHODS: Following PRISMA 2020 guidelines, the PubMed and Scopus databases were searched from inception to June 2023 for studies related to MRI findings in the thalamus of patients with MNDs. Eligible studies included adult patients diagnosed with ALS or other forms of MND who underwent brain MRI, with outcomes related to thalamic alterations. Studies were evaluated for risk of bias using the Newcastle-Ottawa scale.

RESULTS: A total of 52 studies (including 3009 MND patients and 2181 healthy controls) used various MRI techniques, including volumetric analysis, diffusion tensor imaging, and functional MRI, to measure thalamic volume, connectivity, and other alterations. This review confirmed significant thalamic changes in MNDs, such as atrophy and microstructural degradation, which are associated with disease severity, progression, and functional disability. Thalamic involvement varies across different MND subtypes and is influenced by the presence of cognitive impairment and mutations in genes including chromosome 9 open reading frame 72 (C9orf72). The synthesis of findings across studies indicates that thalamic pathology is a prevalent early biomarker of MNDs that contributes to motor and cognitive deficits. The thalamus is a promising target for monitoring as its dysfunction underpins a variety of clinical symptoms in MNDs.

CONCLUSIONS: Thalamic alterations provide valuable insights into the pathophysiology and progression of MNDs. Multimodal MRI techniques are potent tools for detecting dynamic thalamic changes, indicating structural integrity, connectivity disruption, and metabolic activity.}, } @article {pmid38682222, year = {2024}, author = {Huang, Q and Li, Q and Guo, JH}, title = {Causal Relationship between Sex Hormones and Risk of Developing Common Neurodegenerative Diseases: A Mendelian Randomization Study.}, journal = {Journal of integrative neuroscience}, volume = {23}, number = {4}, pages = {78}, doi = {10.31083/j.jin2304078}, pmid = {38682222}, issn = {0219-6352}, support = {2021ZD0201801//Science and Technology Innovation 2030 - Major program of "Brain Science and Brain-like Research"/ ; }, mesh = {Humans ; *Mendelian Randomization Analysis ; *Neurodegenerative Diseases/epidemiology/genetics ; *Sex Hormone-Binding Globulin/analysis/metabolism ; Testosterone/blood ; Alzheimer Disease/epidemiology/genetics ; Estradiol/blood ; Amyotrophic Lateral Sclerosis/epidemiology/genetics ; Parkinson Disease/genetics/epidemiology ; Gonadal Steroid Hormones/blood/metabolism ; Female ; Male ; }, abstract = {BACKGROUND: Neurodegenerative diseases are a group of unexplained disorders of the central nervous system, and studies have shown that a large number of genetic and environmental factors are associated with these diseases. Since these diseases show significant gender differences in epidemiology, sex hormones are thought to be strongly associated with these diseases. In this study, we used Mendelian randomization to explore the causal relationship between sex hormones and the risk of developing neurodegenerative diseases.

METHODS: We obtained genetic instrumental variables for sex hormones (sex hormone-binding globulin [SHBG], estradiol levels [EL], and bioavailable testosterone [BT]) separately through the Integrative Epidemiology Unit (IEU) database (https://gwas.mrcieu.ac.uk/). We analyzed the causal relationship of each with the risk of developing neurodegenerative diseases (Amyotrophic Lateral Sclerosis [ALS], Parkinson's disease [PD], and Alzheimer's disease [AD]) using inverse variance weighted (IVW) in Mendelian randomization. Data were then analyzed for sensitivity.

RESULTS: BT was negatively associated with the risk of developing ALS (odds ratio [OR] = 0.794; 95% confidence interval [95% CI] = 0.672-0.938; p = 0.006). EL and SHBG were not associated with a risk for developing neurodegenerative diseases (ALS, PD, AD).

CONCLUSIONS: Elevated BT is associated with a reduced risk of developing ALS. Further research is needed to investigate the underlying mechanisms of action for this correlation and how it can be used as a potential target of action to reduce the risk of developing ALS.}, } @article {pmid38681726, year = {2024}, author = {Grzanka, M and Joniec, A and Rogulski, J and Sobiech, Ł and Idziak, R and Loryś, B}, title = {Impact of novel herbicide based on synthetic auxins and ALS inhibitor on weed control.}, journal = {Open life sciences}, volume = {19}, number = {1}, pages = {20220868}, pmid = {38681726}, issn = {2391-5412}, abstract = {Delayed sowing of winter cereals or unfavorable weather conditions in autumn may make it impossible to carry out herbicide treatment in autumn. In such cases, weed control should be started in the spring. During this time, the plantation should be protected as effectively as possible because the weeds are at an advanced stage of growth. Therefore, they are less sensitive to applied herbicides. In the treatment, it is worth using a mixture of different mechanisms of action. Studies were conducted to evaluate the effectiveness of a band of tribenuron-methyl, and MCPA applied as soluble granules in spring control of dicotyledonous in winter cereals. The biological efficacy of herbicides was estimated in the 25 field experiments on winter cereals in Poland. Postemergence, a spring application of tribenuron-methyl + MCPA, effectively controls the majority of weed species present in spring: Anthemis arvensis, Brassica napus, Capsella bursa-pastoris, Centaurea cyanus, Lamium purpureum, Matricaria chamomilla, Tripleurospermum inodorum, Stellaria media and Thlaspi arvense. Satisfactory control was confirmed for Veronica persica, Viola arvensis, and Galium aparine. Tribenuron-methyl with MCPA is recommended for application to winter cereals in spring. To prevent the development of resistance in weeds, it is advantageous to combine two active substances.}, } @article {pmid38679739, year = {2024}, author = {Pérez Compte, D and Etourneau, L and Hesse, AM and Kraut, A and Barthelon, J and Sturm, N and Borges, H and Biennier, S and Courçon, M and de Saint Loup, M and Mignot, V and Costentin, C and Burger, T and Couté, Y and Bruley, C and Decaens, T and Jaquinod, M and Boursier, J and Brun, V}, title = {Plasma ALS and Gal-3BP differentiate early from advanced liver fibrosis in MASLD patients.}, journal = {Biomarker research}, volume = {12}, number = {1}, pages = {44}, pmid = {38679739}, issn = {2050-7771}, support = {[ANR-10-INBS-08]//ProFI project/ ; [ANR-10-INBS-08]//ProFI project/ ; [ANR-10-INBS-08]//ProFI project/ ; [ANR-10-INBS-08]//ProFI project/ ; [ANR-10-INBS-08]//ProFI project/ ; [ANR-10-INBS-08]//ProFI project/ ; [ANR-10-INBS-08]//ProFI project/ ; [ANR-10-INBS-08]//ProFI project/ ; [ANR-10-INBS-08]//ProFI project/ ; [ANR-10-INBS-08]//ProFI project/ ; [ANR-10-INBS-08]//ProFI project/ ; [ANR-10-INBS-08]//ProFI project/ ; [ANR-10-INBS-08]//ProFI project/ ; [ANR-10-INBS-08]//ProFI project/ ; [ANR-10-INBS-08]//ProFI project/ ; [ANR-10-INBS-08]//ProFI project/ ; [ANR-10-INBS-08]//ProFI project/ ; [ANR-10-INBS-08]//ProFI project/ ; [ANR-10-INBS-08]//ProFI project/ ; [ANR-17-EURE-0003]//Chemistry Biology Health (CBH) Graduate School at University Grenoble Alpes/ ; [ANR-17-EURE-0003]//Chemistry Biology Health (CBH) Graduate School at University Grenoble Alpes/ ; [ANR-17-EURE-0003]//Chemistry Biology Health (CBH) Graduate School at University Grenoble Alpes/ ; [ANR-17-EURE-0003]//Chemistry Biology Health (CBH) Graduate School at University Grenoble Alpes/ ; [ANR-17-EURE-0003]//Chemistry Biology Health (CBH) Graduate School at University Grenoble Alpes/ ; [ANR-17-EURE-0003]//Chemistry Biology Health (CBH) Graduate School at University Grenoble Alpes/ ; [ANR-17-EURE-0003]//Chemistry Biology Health (CBH) Graduate School at University Grenoble Alpes/ ; [ANR-17-EURE-0003]//Chemistry Biology Health (CBH) Graduate School at University Grenoble Alpes/ ; [ANR-17-EURE-0003]//Chemistry Biology Health (CBH) Graduate School at University Grenoble Alpes/ ; [ANR-17-EURE-0003]//Chemistry Biology Health (CBH) Graduate School at University Grenoble Alpes/ ; [ANR-17-EURE-0003]//Chemistry Biology Health (CBH) Graduate School at University Grenoble Alpes/ ; [ANR-17-EURE-0003]//Chemistry Biology Health (CBH) Graduate School at University Grenoble Alpes/ ; [ANR-17-EURE-0003]//Chemistry Biology Health (CBH) Graduate School at University Grenoble Alpes/ ; [ANR-17-EURE-0003]//Chemistry Biology Health (CBH) Graduate School at University Grenoble Alpes/ ; [ANR-17-EURE-0003]//Chemistry Biology Health (CBH) Graduate School at University Grenoble Alpes/ ; [ANR-17-EURE-0003]//Chemistry Biology Health (CBH) Graduate School at University Grenoble Alpes/ ; [ANR-17-EURE-0003]//Chemistry Biology Health (CBH) Graduate School at University Grenoble Alpes/ ; [ANR-17-EURE-0003]//Chemistry Biology Health (CBH) Graduate School at University Grenoble Alpes/ ; [ANR-17-EURE-0003]//Chemistry Biology Health (CBH) Graduate School at University Grenoble Alpes/ ; [ANR-15-IDEX-02]//LIFE project/ ; [ANR-15-IDEX-02]//LIFE project/ ; [ANR-15-IDEX-02]//LIFE project/ ; [ANR-15-IDEX-02]//LIFE project/ ; [ANR-15-IDEX-02]//LIFE project/ ; [ANR-15-IDEX-02]//LIFE project/ ; [ANR-15-IDEX-02]//LIFE project/ ; [ANR-15-IDEX-02]//LIFE project/ ; [ANR-15-IDEX-02]//LIFE project/ ; [ANR-15-IDEX-02]//LIFE project/ ; [ANR-15-IDEX-02]//LIFE project/ ; [ANR-15-IDEX-02]//LIFE project/ ; [ANR-15-IDEX-02]//LIFE project/ ; [ANR-15-IDEX-02]//LIFE project/ ; [ANR-15-IDEX-02]//LIFE project/ ; [ANR-15-IDEX-02]//LIFE project/ ; [ANR-15-IDEX-02]//LIFE project/ ; [ANR-15-IDEX-02]//LIFE project/ ; [ANR-15-IDEX-02]//LIFE project/ ; [ANR-19-P3IA-0003]//MIAI @ Grenoble Alpes/ ; [ANR-19-P3IA-0003]//MIAI @ Grenoble Alpes/ ; [ANR-19-P3IA-0003]//MIAI @ Grenoble Alpes/ ; [ANR-19-P3IA-0003]//MIAI @ Grenoble Alpes/ ; [ANR-19-P3IA-0003]//MIAI @ Grenoble Alpes/ ; [ANR-19-P3IA-0003]//MIAI @ Grenoble Alpes/ ; [ANR-19-P3IA-0003]//MIAI @ Grenoble Alpes/ ; [ANR-19-P3IA-0003]//MIAI @ Grenoble Alpes/ ; [ANR-19-P3IA-0003]//MIAI @ Grenoble Alpes/ ; [ANR-19-P3IA-0003]//MIAI @ Grenoble Alpes/ ; [ANR-19-P3IA-0003]//MIAI @ Grenoble Alpes/ ; [ANR-19-P3IA-0003]//MIAI @ Grenoble Alpes/ ; [ANR-19-P3IA-0003]//MIAI @ Grenoble Alpes/ ; [ANR-19-P3IA-0003]//MIAI @ Grenoble Alpes/ ; [ANR-19-P3IA-0003]//MIAI @ Grenoble Alpes/ ; [ANR-19-P3IA-0003]//MIAI @ Grenoble Alpes/ ; [ANR-19-P3IA-0003]//MIAI @ Grenoble Alpes/ ; [ANR-19-P3IA-0003]//MIAI @ Grenoble Alpes/ ; [ANR-19-P3IA-0003]//MIAI @ Grenoble Alpes/ ; }, abstract = {BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) is estimated to affect 30% of the world's population, and its prevalence is increasing in line with obesity. Liver fibrosis is closely related to mortality, making it the most important clinical parameter for MASLD. It is currently assessed by liver biopsy - an invasive procedure that has some limitations. There is thus an urgent need for a reliable non-invasive means to diagnose earlier MASLD stages.

METHODS: A discovery study was performed on 158 plasma samples from histologically-characterised MASLD patients using mass spectrometry (MS)-based quantitative proteomics. Differentially abundant proteins were selected for verification by ELISA in the same cohort. They were subsequently validated in an independent MASLD cohort (n = 200).

RESULTS: From the 72 proteins differentially abundant between patients with early (F0-2) and advanced fibrosis (F3-4), we selected Insulin-like growth factor-binding protein complex acid labile subunit (ALS) and Galectin-3-binding protein (Gal-3BP) for further study. In our validation cohort, AUROCs with 95% CIs of 0.744 [0.673 - 0.816] and 0.735 [0.661 - 0.81] were obtained for ALS and Gal-3BP, respectively. Combining ALS and Gal-3BP improved the assessment of advanced liver fibrosis, giving an AUROC of 0.796 [0.731. 0.862]. The {ALS; Gal-3BP} model surpassed classic fibrosis panels in predicting advanced liver fibrosis.

CONCLUSIONS: Further investigations with complementary cohorts will be needed to confirm the usefulness of ALS and Gal-3BP individually and in combination with other biomarkers for diagnosis of liver fibrosis. With the availability of ELISA assays, these findings could be rapidly clinically translated, providing direct benefits for patients.}, } @article {pmid38679111, year = {2024}, author = {Thulasidharan, A and Garg, L and Tendulkar, S and Ratnaparkhi, GS}, title = {Age-dependent dynamics of neuronal VAPB[ALS] inclusions in the adult brain.}, journal = {Neurobiology of disease}, volume = {196}, number = {}, pages = {106517}, doi = {10.1016/j.nbd.2024.106517}, pmid = {38679111}, issn = {1095-953X}, mesh = {Animals ; *Aging/metabolism/pathology/physiology ; *Amyotrophic Lateral Sclerosis/metabolism/pathology/genetics ; Animals, Genetically Modified ; Autophagy/physiology ; *Brain/metabolism/pathology ; Disease Models, Animal ; Drosophila ; *Drosophila Proteins/metabolism/genetics ; *Inclusion Bodies/metabolism/pathology ; Neurons/metabolism/pathology ; Valosin Containing Protein/metabolism/genetics ; }, abstract = {Amyotrophic Lateral Sclerosis (ALS) is a relentlessly progressive and fatal disease, caused by the degeneration of upper and lower motor neurons within the brain and spinal cord in the ageing human. The dying neurons contain cytoplasmic inclusions linked to the onset and progression of the disease. Here, we use a Drosophila model of ALS8 (VAP[P58S]) to understand the modulation of these inclusions in the ageing adult brain. The adult VAP[P58S] fly shows progressive deterioration in motor function till its demise 25 days post-eclosion. The density of VAP[P58S]-positive brain inclusions is stable for 5-15 days of age. In contrast, adding a single copy of VAP[WT] to the VAP[P58S] animal leads to a large decrease in inclusion density with concomitant rescue of motor function and lifespan. ER stress, a contributing factor in disease, shows reduction with ageing for the disease model. Autophagy, rather than the Ubiquitin Proteasome system, is the dominant mechanism for aggregate clearance. We explored the ability of Drosophila Valosin-containing protein (VCP/TER94), the ALS14 locus, which is involved in cellular protein clearance, to regulate age-dependent aggregation. Contrary to expectation, TER94 overexpression increased VAP[P58S] punctae density, while its knockdown led to enhanced clearance. Expression of a dominant positive allele, TER94[R152H], further stabilised VAP[P58S] puncta, cementing roles for an ALS8-ALS14 axis. Our results are explained by a mechanism where autophagy is modulated by TER94 knockdown. Our study sheds light on the complex regulatory events involved in the neuronal maintenance of ALS8 aggregates, suggesting a context-dependent switch between proteasomal and autophagy-based mechanisms as the larvae develop into an adult. A deeper understanding of the nucleation and clearance of the inclusions, which affect cellular stress and function, is essential for understanding the initiation and progression of ALS.}, } @article {pmid38678262, year = {2024}, author = {Xu, C and Mei, Y and Yang, R and Luo, Q and Zhang, J and Kou, X and Hu, J and Wang, Y and Li, Y and Chen, R and Zhang, Z and Yao, Y and Sima, J}, title = {Edaravone Dexborneol mitigates pathology in animal and cell culture models of Alzheimer's disease by inhibiting neuroinflammation and neuronal necroptosis.}, journal = {Cell & bioscience}, volume = {14}, number = {1}, pages = {55}, pmid = {38678262}, issn = {2045-3701}, support = {82173804//National Natural Science Foundation of China/ ; 82001144//National Natural Science Foundation of China/ ; 3150120042//High-Level Talents Start-up Funding of China Pharmaceutical University/ ; }, abstract = {BACKGROUND: Alzheimer's disease (AD) is the most prevalent neurodegenerative disease with limited disease-modifying treatments. Drug repositioning strategy has now emerged as a promising approach for anti-AD drug discovery. Using 5×FAD mice and Aβ-treated neurons in culture, we tested the efficacy of Y-2, a compounded drug containing the antioxidant Edaravone (Eda), a pyrazolone and (+)-Borneol, an anti-inflammatory diterpenoid from cinnamon, approved for use in amyotrophic lateral sclerosis patients.

RESULTS: We examined effects of Y-2 versus Eda alone by i.p. administered in 8-week-old 5×FAD mice (females) for 4 months by comparing cognitive function, Aβ pathologies, neuronal necroptosis and neuroinflammation. Using primary neurons and astrocytes, as well as neuronal and astrocytic cell lines, we elucidated the molecular mechanisms of Y-2 by examining neuronal injury, astrocyte-mediated inflammation and necroptosis. Here, we find that Y-2 improves cognitive function in AD mice. Histopathological data show that Y-2, better than Eda alone, markedly ameliorates Aβ pathologies including Aβ burden, astrogliosis/microgliosis, and Tau phosphorylation. In addition, Y-2 reduces Aβ-induced neuronal injury including neurite damage, mitochondrial impairment, reactive oxygen species production and NAD[+] depletion. Notably, Y-2 inhibits astrocyte-mediated neuroinflammation and attenuates TNF-α-triggered neuronal necroptosis in cell cultures and AD mice. RNA-seq further demonstrates that Y-2, compared to Eda, indeed upregulates anti-inflammation pathways in astrocytes.

CONCLUSIONS: Our findings infer that Y-2, better than Eda alone, mitigates AD pathology and may provide a potential drug candidate for AD treatment.}, } @article {pmid38677733, year = {2024}, author = {Keul, J and Sperling, S and Rohde, V and Mielke, D and Ninkovic, M}, title = {Riluzole Reverses a Number of Undesirable Effects of Dexamethasone in Glioblastoma Cells.}, journal = {Anticancer research}, volume = {44}, number = {5}, pages = {1829-1835}, doi = {10.21873/anticanres.16984}, pmid = {38677733}, issn = {1791-7530}, mesh = {*Riluzole/pharmacology ; Humans ; *Glioblastoma/drug therapy/pathology/metabolism ; *Dexamethasone/pharmacology ; *Cell Movement/drug effects ; Cell Line, Tumor ; Brain Neoplasms/drug therapy/pathology/metabolism ; Cell Survival/drug effects ; }, abstract = {BACKGROUND/AIM: Glioblastoma multiforme (GBM)-induced oedema is a major cause of morbidity and mortality among patients with GBM. Dexamethasone (Dex) is the most common corticosteroid used pre-operatively to control cerebral oedema in patients with GBM. Dex is associated with many side effects, and shorter overall survival and progression-free survival of patients with GBM. These negative effects of Dex highlight the need for combinational therapy. Riluzole (Ril), a drug used to treat amyotrophic lateral sclerosis (ALS), is thought to have potential as a treatment for various cancers, with clinical trials underway. Here, we investigated whether Ril could reverse some of the undesirable effects of Dex.

MATERIALS AND METHODS: The effect of Dex, Ril, and Ril-Dex treatment on cell migration was monitored using the xCELLigence system. Cell viability assays were performed using 3-(4, 5-dimethylthiazol)-2, 5-diphenyltetrazolium bromide (MTT). The expression of genes involved in migration, glucose metabolism, and stemness was examined using real-time polymerase chain reaction (PCR).

RESULTS: Pre-treating GBM cells with Ril reduced Dex-induced cell migration and altered Dex-induced effects on cell invasion, stem cell, and glucose metabolism markers. Furthermore, Ril remained effective in killing GBM cells in combination with Dex.

CONCLUSION: Ril, which acts as an anti-tumorigenic drug, mediates some of the negative effects of Dex; therefore, it could be a potential drug to manage the side effects of Dex therapy in GBM.}, } @article {pmid38677657, year = {2024}, author = {Ko, VI and Ong, K and Cleveland, DW and Yu, H and Ravits, JM}, title = {CK1δ/ε kinases regulate TDP-43 phosphorylation and are therapeutic targets for ALS-related TDP-43 hyperphosphorylation.}, journal = {Neurobiology of disease}, volume = {196}, number = {}, pages = {106516}, doi = {10.1016/j.nbd.2024.106516}, pmid = {38677657}, issn = {1095-953X}, mesh = {Phosphorylation ; *DNA-Binding Proteins/metabolism ; *Amyotrophic Lateral Sclerosis/metabolism/drug therapy ; Humans ; *Casein Kinase Idelta/metabolism ; *Casein Kinase 1 epsilon/metabolism ; HEK293 Cells ; }, abstract = {Hyperphosphorylated TAR DNA-binding protein 43 (TDP-43) aggregates in the cytoplasm of neurons is the neuropathological hallmark of amyotrophic lateral sclerosis (ALS) and a group of neurodegenerative diseases collectively referred to as TDP-43 proteinopathies that includes frontotemporal dementia, Alzheimer's disease, and limbic onset age-related TDP-43 encephalopathy. The mechanism of TDP-43 phosphorylation is poorly understood. Previously we reported casein kinase 1 epsilon gene (CSNK1E gene encoding CK1ε protein) as being tightly correlated with phosphorylated TDP-43 (pTDP-43) pathology. Here we pursued studies to investigate in cellular models and in vitro how CK1ε and CK1δ (a closely related family sub-member) mediate TDP-43 phosphorylation in disease. We first validated the binding interaction between TDP-43 and either CK1δ and CK1ε using kinase activity assays and predictive bioinformatic database. We utilized novel inducible cellular models that generated translocated phosphorylated TDP-43 (pTDP-43) and cytoplasmic aggregation. Reducing CK1 kinase activity with siRNA or small molecule chemical inhibitors resulted in significant reduction of pTDP-43, in both soluble and insoluble protein fractions. We also established CK1δ and CK1ε are the primary kinases that phosphorylate TDP-43 compared to CK2α, CDC7, ERK1/2, p38α/MAPK14, and TTBK1, other identified kinases that have been implicated in TDP-43 phosphorylation. Throughout our studies, we were careful to examine both the soluble and insoluble TDP-43 protein fractions, the critical protein fractions related to protein aggregation diseases. These results identify CK1s as critical kinases involved in TDP-43 hyperphosphorylation and aggregation in cellular models and in vitro, and in turn are potential therapeutic targets by way of CK1δ/ε inhibitors.}, } @article {pmid38676818, year = {2024}, author = {Kubat, GB and Picone, P}, title = {Skeletal muscle dysfunction in amyotrophic lateral sclerosis: a mitochondrial perspective and therapeutic approaches.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {45}, number = {9}, pages = {4121-4131}, pmid = {38676818}, issn = {1590-3478}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy/physiopathology/pathology ; *Muscle, Skeletal/physiopathology/pathology ; Animals ; Mitochondria/metabolism ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neuromuscular disease that results in the loss of motor neurons and severe skeletal muscle atrophy. The etiology of ALS is linked to skeletal muscle, which can activate a retrograde signaling cascade that destroys motor neurons. This is why satellite cells and mitochondria play a crucial role in the health and performance of skeletal muscles. This review presents current knowledge on the involvement of mitochondrial dysfunction, skeletal muscle atrophy, muscle satellite cells, and neuromuscular junction (NMJ) in ALS. It also discusses current therapeutic strategies, including exercise, drugs, stem cells, gene therapy, and the prospective use of mitochondrial transplantation as a viable therapeutic strategy.}, } @article {pmid38676672, year = {2024}, author = {Kutlubaev, MA}, title = {[Promising approaches to the pathogenetic therapy of amyotrophic lateral sclerosis].}, journal = {Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova}, volume = {124}, number = {4}, pages = {13-21}, doi = {10.17116/jnevro202412404113}, pmid = {38676672}, issn = {1997-7298}, mesh = {*Amyotrophic Lateral Sclerosis/drug therapy/therapy ; Humans ; *Neuroprotective Agents/therapeutic use ; Genetic Therapy ; Antioxidants/therapeutic use ; Stem Cell Transplantation ; Gastrointestinal Microbiome ; Immunologic Factors/therapeutic use ; Immunomodulating Agents/therapeutic use ; }, abstract = {Amyotrophic lateral sclerosis is a severe incurable disease of the nervous system. Currently only methods of palliative care for the patients with this disease are available. Few medications for the pathogenetic therapy are registered in some countries, i.e. riluzole, edaravon, sodium phenylbutyrate/taurursodiol as well as tofersen (conditionally). Their efficacy is relatively low. The main directions in the development of pathogenetic therapy of ALS include gene therapy, use of stem cells, immunomodulators, agents affecting gut microbiota. A search is also underway for low-molecular compounds with neuroprotective and antioxidant properties. Perspective direction is prevention of ALS. This will be possible when biomarkers for identification of patients in pre-manifest/prodromal stage are detected.}, } @article {pmid38676626, year = {2024}, author = {Dash, BP and Freischmidt, A and Weishaupt, JH and Hermann, A}, title = {An integrative miRNA-mRNA expression analysis identifies miRNA signatures associated with SOD1 and TARDBP patient-derived motor neurons.}, journal = {Human molecular genetics}, volume = {33}, number = {15}, pages = {1300-1314}, doi = {10.1093/hmg/ddae072}, pmid = {38676626}, issn = {1460-2083}, support = {//Hermann and Lilly Schilling-Stiftung für medizinische Forschung im Stifterverband/ ; //Professorinnenprogramm III (University of Rostock) of the German/ ; }, mesh = {*MicroRNAs/genetics ; Humans ; *Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology ; *Motor Neurons/metabolism/pathology ; *Superoxide Dismutase-1/genetics/metabolism ; *RNA, Messenger/genetics/metabolism ; *DNA-Binding Proteins/genetics/metabolism ; *Induced Pluripotent Stem Cells/metabolism ; Gene Expression Profiling ; Gene Expression Regulation/genetics ; Transcriptome/genetics ; }, abstract = {MicroRNAs (miRNAs) are a subset of small non-coding single-stranded RNA molecules involved in the regulation of post-transcriptional gene expression of a variety of transcript targets. Therefore altered miRNA expression may result in the dysregulation of key genes and biological pathways that has been reported with the onset and progression of neurodegenerative diseases, such as Amyotrophic lateral sclerosis (ALS). ALS is marked by a progressive degeneration of motor neurons (MNs) present in the spinal cord, brain stem and motor cortex. Although the pathomechanism underlying molecular interactions of ALS remains poorly understood, alterations in RNA metabolism, including dysregulation of miRNA expression in familial as well as sporadic forms are still scarcely studied. In this study, we performed combined transcriptomic data and miRNA profiling in MN samples of the same samples of iPSC-derived MNs from SOD1- and TARDBP (TDP-43 protein)-mutant-ALS patients and healthy controls. We report a global upregulation of mature miRNAs, and suggest that differentially expressed (DE) miRNAs have a significant impact on mRNA-level in SOD1-, but not in TARDBP-linked ALS. Furthermore, in SOD1-ALS we identified dysregulated miRNAs such as miR-124-3p, miR-19b-3p and miR-218 and their potential targets previously implicated in important functional process and pathogenic pathways underlying ALS. These miRNAs may play key roles in the neuronal development and cell survival related functions in SOD1-ALS. Altogether, we provide evidence of miRNA regulated genes expression mainly in SOD1 rather than TDP43-ALS.}, } @article {pmid38676602, year = {2024}, author = {Presotto, A and Hernández, F and Vercellino, RB and Kruger, RD and Fontana, ML and Ureta, MS and Crepy, M and Auge, G and Caicedo, A}, title = {Introgression from local cultivars is a driver of agricultural adaptation in Argentinian weedy rice.}, journal = {Molecular ecology}, volume = {33}, number = {11}, pages = {e17368}, doi = {10.1111/mec.17368}, pmid = {38676602}, issn = {1365-294X}, support = {IOS-1032023//Division of Integrative Organismal Systems/ ; PICT 2019-00581//Agencia Nacional de Promoción de la Investigación, el Desarrollo Tecnológico y la Innovación/ ; }, mesh = {*Oryza/genetics ; *Herbicide Resistance/genetics ; Argentina ; *Acetolactate Synthase/genetics ; *Herbicides ; Plant Weeds/genetics ; Phenotype ; Genotype ; Adaptation, Physiological/genetics ; Crops, Agricultural/genetics ; Gene Flow ; Agriculture ; Mutation ; }, abstract = {Weedy rice, a pervasive and troublesome weed found across the globe, has often evolved through fertilization of rice cultivars with little importance of crop-weed gene flow. In Argentina, weedy rice has been reported as an important constraint since the early 1970s, and, in the last few years, strains with herbicide-resistance are suspected to evolve. Despite their importance, the origin and genetic composition of Argentinian weedy rice as well its adaptation to agricultural environments has not been explored so far. To study this, we conducted genotyping-by-sequencing on samples of Argentinian weedy and cultivated rice and compared them with published data from weedy, cultivated and wild rice accessions distributed worldwide. In addition, we conducted a phenotypic characterization for weedy-related traits, a herbicide resistance screening and genotyped accessions for known mutations in the acetolactate synthase (ALS) gene, which confers herbicide resistance. Our results revealed large phenotypic variability in Argentinian weedy rice. Most strains were resistant to ALS-inhibiting herbicides with a high frequency of the ALS mutation (A122T) present in Argentinian rice cultivars. Argentinian cultivars belonged to the three major genetic groups of rice: japonica, indica and aus while weeds were mostly aus or aus-indica admixed, resembling weedy rice strains from the Southern Cone region. Phylogenetic analysis supports a single origin for aus-like South American weeds, likely as seed contaminants from the United States, and then admixture with local indica cultivars. Our findings demonstrate that crop to weed introgression can facilitate rapid adaptation to agriculture environments.}, } @article {pmid38676303, year = {2024}, author = {Zhao, W and Wang, R and Chen, M}, title = {Clinical analysis of air-leak syndrome following allogeneic hematopoietic stem cell transplantation in pediatric patients.}, journal = {Pediatric blood & cancer}, volume = {71}, number = {7}, pages = {e31008}, doi = {10.1002/pbc.31008}, pmid = {38676303}, issn = {1545-5017}, mesh = {Humans ; *Hematopoietic Stem Cell Transplantation/adverse effects ; Male ; Female ; Retrospective Studies ; Child ; Child, Preschool ; Adolescent ; Infant ; Prognosis ; Survival Rate ; Follow-Up Studies ; Transplantation, Homologous ; Bronchiolitis Obliterans/etiology/mortality/therapy ; Pneumonia/etiology/mortality ; }, abstract = {BACKGROUND: Air-leak syndrome (ALS) is considered as an independent risk factor for poor prognosis in adult patients who had received hematopoietic stem cell transplantation (HSCT), and the 5-year overall survival (OS) of ALS is less than 30%. However, the clinical features of ALS among post-transplant pediatric patients have rarely been explored.

PROCEDURES: We retrospectively reviewed 2206 pediatric patients who had received an allo-HSCT between January 2013 and December 2019 at the Hebei Yanda Lu Daopei Hospital, and analyzed the role of ALS in prognosis following HSCT.

RESULTS: In our research, ALS was divided into two categories: 15 cases of bronchiolitis obliterans syndrome (BOS) and 13 cases of idiopathic pneumonia syndrome (IPS). Following treatment of the ALS, 18 patients survived (18/28, 64.3%), and 10 patients died of respiratory failure or infection (10/28, 35.7%).

CONCLUSIONS: The OS of ALS in Hebei Yanda Lu Daopei Hospital is significantly higher than others, and they were cited to be related to early diagnosis and timely FAM treatment in previous reports.}, } @article {pmid38675428, year = {2024}, author = {Calenda, S and Catarzi, D and Varano, F and Vigiani, E and Volpini, R and Lambertucci, C and Spinaci, A and Trevisan, L and Grieco, I and Federico, S and Spalluto, G and Novello, G and Salmaso, V and Moro, S and Colotta, V}, title = {Structural Investigations on 2-Amidobenzimidazole Derivatives as New Inhibitors of Protein Kinase CK1 Delta.}, journal = {Pharmaceuticals (Basel, Switzerland)}, volume = {17}, number = {4}, pages = {}, pmid = {38675428}, issn = {1424-8247}, support = {RICATEN2021-2023Colotta//University of Florence/ ; 2017MT3993_004//Italian Ministry of University and Research-PRIN2017/ ; }, abstract = {Protein kinase CK1δ (CK1δ) is a serine-threonine/kinase that modulates different physiological processes, including the cell cycle, DNA repair, and apoptosis. CK1δ overexpression, and the consequent hyperphosphorylation of specific proteins, can lead to sleep disorders, cancer, and neurodegenerative diseases. CK1δ inhibitors showed anticancer properties as well as neuroprotective effects in cellular and animal models of Parkinson's and Alzheimer's diseases and amyotrophic lateral sclerosis. To obtain new ATP-competitive CK1δ inhibitors, three sets of benzimidazole-2-amino derivatives were synthesized (1-32), bearing different substituents on the fused benzo ring (R) and diverse pyrazole-containing acyl moieties on the 2-amino group. The best-performing derivatives were those featuring the (1H-pyrazol-3-yl)-acetyl moiety on the benzimidazol-2-amino scaffold (13-32), which showed CK1δ inhibitor activity in the low micromolar range. Among the R substituents, 5-cyano was the most advantageous, leading to a compound endowed with nanomolar potency (23, IC50 = 98.6 nM). Molecular docking and dynamics studies were performed to point out the inhibitor-kinase interactions.}, } @article {pmid38674921, year = {2024}, author = {Wang, W and Pan, D and Liu, Q and Chen, X and Wang, S}, title = {L-Carnitine in the Treatment of Psychiatric and Neurological Manifestations: A Systematic Review.}, journal = {Nutrients}, volume = {16}, number = {8}, pages = {}, pmid = {38674921}, issn = {2072-6643}, mesh = {Humans ; *Carnitine/therapeutic use ; Dietary Supplements ; *Mental Disorders/drug therapy ; *Nervous System Diseases/drug therapy ; }, abstract = {OBJECTIVE: L-carnitine (LC), a vital nutritional supplement, plays a crucial role in myocardial health and exhibits significant cardioprotective effects. LC, being the principal constituent of clinical-grade supplements, finds extensive application in the recovery and treatment of diverse cardiovascular and cerebrovascular disorders. However, controversies persist regarding the utilization of LC in nervous system diseases, with varying effects observed across numerous mental and neurological disorders. This article primarily aims to gather and analyze database information to comprehensively summarize the therapeutic potential of LC in patients suffering from nervous system diseases while providing valuable references for further research.

METHODS: A comprehensive search was conducted in PubMed, Web Of Science, Embase, Ovid Medline, Cochrane Library and Clinicaltrials.gov databases. The literature pertaining to the impact of LC supplementation on neurological or psychiatric disorders in patients was reviewed up until November 2023. No language or temporal restrictions were imposed on the search.

RESULTS: A total of 1479 articles were retrieved, and after the removal of duplicates through both automated and manual exclusion processes, 962 articles remained. Subsequently, a meticulous re-screening led to the identification of 60 relevant articles. Among these, there were 12 publications focusing on hepatic encephalopathy (HE), while neurodegenerative diseases (NDs) and peripheral nervous system diseases (PNSDs) were represented by 9 and 6 articles, respectively. Additionally, stroke was addressed in five publications, whereas Raynaud's syndrome (RS) and cognitive disorder (CD) each had three dedicated studies. Furthermore, migraine, depression, and amyotrophic lateral sclerosis (ALS) each accounted for two publications. Lastly, one article was found for other symptoms under investigation.

CONCLUSION: In summary, LC has demonstrated favorable therapeutic effects in the management of HE, Alzheimer's disease (AD), carpal tunnel syndrome (CTS), CD, migraine, neurofibromatosis (NF), PNSDs, RS, and stroke. However, its efficacy appears to be relatively limited in conditions such as ALS, ataxia, attention deficit hyperactivity disorder (ADHD), depression, chronic fatigue syndrome (CFS), Down syndrome (DS), and sciatica.}, } @article {pmid38674548, year = {2024}, author = {Bai, L and Li, X and Guo, X and Chen, J and Yu, H and Cui, H}, title = {Distribution and Mechanism of Japanese Brome (Bromus japonicus) Resistance to ALS-Inhibiting Herbicides in China.}, journal = {Plants (Basel, Switzerland)}, volume = {13}, number = {8}, pages = {}, pmid = {38674548}, issn = {2223-7747}, support = {2023YFD1400501//National Key Research and Development Program of China and Technology Innovation Project, Chinese Academy of Agricultural Sciences./ ; }, abstract = {Bromus japonicus is a common monocot weed that occurs in major winter wheat fields in the Huang-Huai-Hai region of China. Pyroxsulam is a highly efficient and safe acetolactate synthase (ALS)-inhibiting herbicide that is widely used to control common weeds in wheat fields. However, B. japonicus populations in China have evolved resistance to pyroxsulam by different mutations in the ALS gene. To understand the resistance distribution, target-site resistance mechanisms, and cross-resistance patterns, 208 B. japonicus populations were collected from eight provinces. In the resistant population screening experiment, 59 populations from six provinces showed different resistance levels to pyroxsulam compared with the susceptible population, of which 17 B. japonicus populations with moderate or high levels of resistance to pyroxsulam were mainly from the Hebei (4), Shandong (4) and Shanxi (9) Provinces. Some resistant populations were selected to investigate the target site-resistance mechanism to the ALS-inhibiting herbicide pyroxsulam. Three pairs of primers were designed to amplify the ALS sequence, which was assembled into the complete ALS sequence with a length of 1932 bp. DNA sequencing of ALS revealed that four different ALS mutations (Pro-197-Ser, Pro-197-Thr, Pro-197-Phe and Asp-376-Glu) were found in 17 moderately or highly resistant populations. Subsequently, five resistant populations, QM21-41 with Pro-197-Ser, QM20-8 with Pro-197-Thr and Pro-197-Phe, and QM21-72, QM21-76 and QM21-79 with Asp-376-Glu mutations in ALS genes, were selected to characterize their cross-resistance patterns to ALS inhibitors. The QM21-41, QM20-8, QM21-72, QM21-76 and QM21-79 populations showed broad-spectrum cross-resistance to pyroxsulam, mesosulfuron-methyl and flucarbazone-sodium. This study is the first to report evolving cross-resistance to ALS-inhibiting herbicides due to Pro-197-Phe mutations in B. japonicus.}, } @article {pmid38674431, year = {2024}, author = {Shahim, P and Norato, G and Sinaii, N and Zetterberg, H and Blennow, K and Chan, L and Grunseich, C}, title = {Neurofilaments in Sporadic and Familial Amyotrophic Lateral Sclerosis: A Systematic Review and Meta-Analysis.}, journal = {Genes}, volume = {15}, number = {4}, pages = {}, pmid = {38674431}, issn = {2073-4425}, mesh = {*Amyotrophic Lateral Sclerosis/genetics/blood/diagnosis/cerebrospinal fluid ; Humans ; *Neurofilament Proteins/blood/cerebrospinal fluid ; Biomarkers/blood/cerebrospinal fluid ; Intermediate Filaments/metabolism/genetics ; Prognosis ; }, abstract = {BACKGROUND: Neurofilament proteins have been implicated to be altered in amyotrophic lateral sclerosis (ALS). The objectives of this study were to assess the diagnostic and prognostic utility of neurofilaments in ALS.

METHODS: Studies were conducted in electronic databases (PubMed/MEDLINE, Embase, Web of Science, and Cochrane CENTRAL) from inception to 17 August 2023, and investigated neurofilament light (NfL) or phosphorylated neurofilament heavy chain (pNfH) in ALS. The study design, enrolment criteria, neurofilament concentrations, test accuracy, relationship between neurofilaments in cerebrospinal fluid (CSF) and blood, and clinical outcome were recorded. The protocol was registered with PROSPERO, CRD42022376939.

RESULTS: Sixty studies with 8801 participants were included. Both NfL and pNfH measured in CSF showed high sensitivity and specificity in distinguishing ALS from disease mimics. Both NfL and pNfH measured in CSF correlated with their corresponding levels in blood (plasma or serum); however, there were stronger correlations between CSF NfL and blood NfL. NfL measured in blood exhibited high sensitivity and specificity in distinguishing ALS from controls. Both higher levels of NfL and pNfH either measured in blood or CSF were correlated with more severe symptoms as assessed by the ALS Functional Rating Scale Revised score and with a faster disease progression rate; however, only blood NfL levels were associated with shorter survival.

DISCUSSION: Both NfL and pNfH measured in CSF or blood show high diagnostic utility and association with ALS functional scores and disease progression, while CSF NfL correlates strongly with blood (either plasma or serum) and is also associated with survival, supporting its use in clinical diagnostics and prognosis. Future work must be conducted in a prospective manner with standardized bio-specimen collection methods and analytical platforms, further improvement in immunoassays for quantification of pNfH in blood, and the identification of cut-offs across the ALS spectrum and controls.}, } @article {pmid38672445, year = {2024}, author = {Esperante, IJ and Meyer, M and Banzan, C and Kruse, MS and Lima, A and Roig, P and Guennoun, R and Schumacher, M and De Nicola, AF and Gonzalez Deniselle, MC}, title = {Testosterone Reduces Myelin Abnormalities in the Wobbler Mouse Model of Amyotrophic Lateral Sclerosis.}, journal = {Biomolecules}, volume = {14}, number = {4}, pages = {}, pmid = {38672445}, issn = {2218-273X}, support = {PICT 2019 Nº 3292//Ministerio de Ciencia, Tecnología e Innovación/ ; PIP 2022-2024 #11220210100091CO//CONICET/ ; }, mesh = {Animals ; Mice ; *Myelin Sheath/metabolism/drug effects ; *Amyotrophic Lateral Sclerosis/drug therapy/metabolism/pathology ; Male ; *Disease Models, Animal ; *Testosterone/pharmacology ; Spinal Cord/metabolism/drug effects/pathology ; Excitatory Amino Acid Transporter 2/metabolism/genetics ; Microglia/drug effects/metabolism/pathology ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal motoneuron degenerative disease that is associated with demyelination. The Wobbler (WR) mouse exhibits motoneuron degeneration, gliosis and myelin deterioration in the cervical spinal cord. Since male WRs display low testosterone (T) levels in the nervous system, we investigated if T modified myelin-relative parameters in WRs in the absence or presence of the aromatase inhibitor, anastrozole (A). We studied myelin by using luxol-fast-blue (LFB) staining, semithin sections, electron microscopy and myelin protein expression, density of IBA1[+] microglia and mRNA expression of inflammatory factors, and the glutamatergic parameters glutamine synthetase (GS) and the transporter GLT1. Controls and WR + T showed higher LFB, MBP and PLP staining, lower g-ratios and compact myelin than WRs and WR + T + A, and groups showing the rupture of myelin lamellae. WRs showed increased IBA1[+] cells and mRNA for CD11b and inflammatory factors (IL-18, TLR4, TNFαR1 and P2Y12R) vs. controls or WR + T. IBA1[+] cells, and CD11b were not reduced in WR + T + A, but inflammatory factors' mRNA remained low. A reduction of GS[+] cells and GLT-1 immunoreactivity was observed in WRs and WR + T + A vs. controls and WR + T. Clinically, WR + T but not WR + T + A showed enhanced muscle mass, grip strength and reduced paw abnormalities. Therefore, T effects involve myelin protection, a finding of potential clinical translation.}, } @article {pmid38672428, year = {2024}, author = {Cox, SN and Lo Giudice, C and Lavecchia, A and Poeta, ML and Chiara, M and Picardi, E and Pesole, G}, title = {Mitochondrial and Nuclear DNA Variants in Amyotrophic Lateral Sclerosis: Enrichment in the Mitochondrial Control Region and Sirtuin Pathway Genes in Spinal Cord Tissue.}, journal = {Biomolecules}, volume = {14}, number = {4}, pages = {}, pmid = {38672428}, issn = {2218-273X}, support = {UNIBA148- project code C1A93B75-CUP H94I20000410008//Research for Innovation (REFIN)-POR PUGLIA FESR-FSE 2014/2020/ ; CN_00000013//National Research Centers: "High Performance Computing, Big Data and Quantum Computing"/ ; CN_00000041//National Research Centers: "Gene Therapy and Drugs based on RNA Technology"/ ; PE_0000006//National Research Centers-Extended Partnerships: MNESYS/ ; IR0000010//ELIXIR-IT ELIXIRNextGenIT/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/genetics/metabolism ; Humans ; *Spinal Cord/metabolism/pathology ; *DNA, Mitochondrial/genetics ; *Sirtuins/genetics/metabolism ; Male ; Female ; Middle Aged ; Mitochondria/genetics/metabolism ; Cell Nucleus/genetics/metabolism ; Aged ; Exome Sequencing ; }, abstract = {Amyotrophic Lateral Sclerosis (ALS) is a progressive disease with prevalent mitochondrial dysfunctions affecting both upper and lower motor neurons in the motor cortex, brainstem, and spinal cord. Despite mitochondria having their own genome (mtDNA), in humans, most mitochondrial genes are encoded by the nuclear genome (nDNA). Our study aimed to simultaneously screen for nDNA and mtDNA genomes to assess for specific variant enrichment in ALS compared to control tissues. Here, we analysed whole exome (WES) and whole genome (WGS) sequencing data from spinal cord tissues, respectively, of 6 and 12 human donors. A total of 31,257 and 301,241 variants in nuclear-encoded mitochondrial genes were identified from WES and WGS, respectively, while mtDNA reads accounted for 73 and 332 variants. Despite technical differences, both datasets consistently revealed a specific enrichment of variants in the mitochondrial Control Region (CR) and in several of these genes directly associated with mitochondrial dynamics or with Sirtuin pathway genes within ALS tissues. Overall, our data support the hypothesis of a variant burden in specific genes, highlighting potential actionable targets for therapeutic interventions in ALS.}, } @article {pmid38672416, year = {2024}, author = {Cheslow, L and Snook, AE and Waldman, SA}, title = {Biomarkers for Managing Neurodegenerative Diseases.}, journal = {Biomolecules}, volume = {14}, number = {4}, pages = {}, pmid = {38672416}, issn = {2218-273X}, support = {F30 NS125921/NS/NINDS NIH HHS/United States ; R01 DK138834/DK/NIDDK NIH HHS/United States ; R21 NS130388/NS/NINDS NIH HHS/United States ; 1R01 CA204881, 1R01 CA206026, 1R21 1NS130388, 1R01 DK1388341/NH/NIH HHS/United States ; }, mesh = {Humans ; *Biomarkers/metabolism ; *Neurodegenerative Diseases/metabolism/diagnosis/therapy ; *Alzheimer Disease/metabolism/diagnosis/therapy ; Amyotrophic Lateral Sclerosis/metabolism/therapy/diagnosis ; Parkinson Disease/metabolism/diagnosis/therapy ; Animals ; }, abstract = {Neurological disorders are the leading cause of cognitive and physical disability worldwide, affecting 15% of the global population. Due to the demographics of aging, the prevalence of neurological disorders, including neurodegenerative diseases, will double over the next two decades. Unfortunately, while available therapies provide symptomatic relief for cognitive and motor impairment, there is an urgent unmet need to develop disease-modifying therapies that slow the rate of pathological progression. In that context, biomarkers could identify at-risk and prodromal patients, monitor disease progression, track responses to therapy, and parse the causality of molecular events to identify novel targets for further clinical investigation. Thus, identifying biomarkers that discriminate between diseases and reflect specific stages of pathology would catalyze the discovery and development of therapeutic targets. This review will describe the prevalence, known mechanisms, ongoing or recently concluded therapeutic clinical trials, and biomarkers of three of the most prevalent neurodegenerative diseases, including Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), and Parkinson's disease (PD).}, } @article {pmid38672412, year = {2024}, author = {Lachén-Montes, M and Cartas-Cejudo, P and Cortés, A and Anaya-Cubero, E and Peral, E and Ausín, K and Díaz-Peña, R and Fernández-Irigoyen, J and Santamaría, E}, title = {Involvement of Glucosamine 6 Phosphate Isomerase 2 (GNPDA2) Overproduction in β-Amyloid- and Tau P301L-Driven Pathomechanisms.}, journal = {Biomolecules}, volume = {14}, number = {4}, pages = {}, pmid = {38672412}, issn = {2218-273X}, support = {0011-1411-2020-000028 and 0011-1411-2023-000028//Gobierno de Navarra/ ; PID2019-110356RB-I00/AEI/10.13039/501100011033//Spanish Ministry of Science, Innovation and Universities/ ; }, mesh = {Animals ; Humans ; *Aldose-Ketose Isomerases/metabolism/genetics ; *Alzheimer Disease/metabolism/genetics/pathology ; *Amyloid beta-Peptides/metabolism ; Animals, Genetically Modified ; Cell Proliferation ; Epithelial Cells/metabolism ; Proteomics ; *tau Proteins/metabolism/genetics ; *Zebrafish/metabolism ; }, abstract = {Alzheimer's disease (AD) is a neurodegenerative olfactory disorder affecting millions of people worldwide. Alterations in the hexosamine- or glucose-related pathways have been described through AD progression. Specifically, an alteration in glucosamine 6 phosphate isomerase 2 (GNPDA2) protein levels has been observed in olfactory areas of AD subjects. However, the biological role of GNPDA2 in neurodegeneration remains unknown. Using mass spectrometry, multiple GNPDA2 interactors were identified in human nasal epithelial cells (NECs) mainly involved in intraciliary transport. Moreover, GNPDA2 overexpression induced an increment in NEC proliferation rates, accompanied by transcriptomic alterations in Type II interferon signaling or cellular stress responses. In contrast, the presence of beta-amyloid or mutated Tau-P301L in GNPDA2-overexpressing NECs induced a slowdown in the proliferative capacity in parallel with a disruption in protein processing. The proteomic characterization of Tau-P301L transgenic zebrafish embryos demonstrated that GNPDA2 overexpression interfered with collagen biosynthesis and RNA/protein processing, without inducing additional changes in axonal outgrowth defects or neuronal cell death. In humans, a significant increase in serum GNPDA2 levels was observed across multiple neurological proteinopathies (AD, Lewy body dementia, progressive supranuclear palsy, mixed dementia and amyotrophic lateral sclerosis) (n = 215). These data shed new light on GNPDA2-dependent mechanisms associated with the neurodegenerative process beyond the hexosamine route.}, } @article {pmid38671434, year = {2024}, author = {Ohlenburg, H and Arnemann, PH and Hessler, M and Görlich, D and Zarbock, A and Friederichs, H}, title = {Flipped Classroom: Improved team performance during resuscitation training through interactive pre-course content - a cluster-randomised controlled study.}, journal = {BMC medical education}, volume = {24}, number = {1}, pages = {459}, pmid = {38671434}, issn = {1472-6920}, mesh = {Humans ; *Patient Care Team ; *Resuscitation/education ; Female ; Male ; *Curriculum ; Germany ; Clinical Competence ; Problem-Based Learning ; Students, Medical ; Education, Medical, Undergraduate/methods ; Adult ; Educational Measurement ; Simulation Training ; }, abstract = {BACKGROUND: Resuscitation is a team effort, and it is increasingly acknowledged that team cooperation requires training. Staff shortages in many healthcare systems worldwide, as well as recent pandemic restrictions, limit opportunities for collaborative team training. To address this challenge, a learner-centred approach known as flipped learning has been successfully implemented. This model comprises self-directed, asynchronous pre-course learning, followed by knowledge application and skill training during in-class sessions. The existing evidence supports the effectiveness of this approach for the acquisition of cognitive skills, but it is uncertain whether the flipped classroom model is suitable for the acquisition of team skills. The objective of this study was to determine if a flipped classroom approach, with an online workshop prior to an instructor-led course could improve team performance and key resuscitation variables during classroom training.

METHODS: A single-centre, cluster-randomised, rater-blinded study was conducted on 114 final year medical students at a University Hospital in Germany. The study randomly assigned students to either the intervention or control group using a computer script. Each team, regardless of group, performed two advanced life support (ALS) scenarios on a simulator. The two groups differed in the order in which they completed the flipped e-learning curriculum. The intervention group started with the e-learning component, and the control group started with an ALS scenario. Simulators were used for recording and analysing resuscitation performance indicators, while professionals assessed team performance as a primary outcome.

RESULTS: The analysis was conducted on the data of 96 participants in 21 teams, comprising of 11 intervention groups and 10 control groups. The intervention teams achieved higher team performance ratings during the first scenario compared to the control teams (Estimated marginal mean of global rating: 7.5 vs 5.6, p < 0.01; performance score: 4.4 vs 3.8, p < 0.05; global score: 4.4 vs 3.7, p < 0.001). However, these differences were not observed in the second scenario, where both study groups had used the e-learning tool.

CONCLUSION: Flipped classroom approaches using learner-paced e-learning prior to hands-on training can improve team performance.

TRIAL REGISTRATION: German Clinical Trials Register (https://drks.de/search/de/trial/DRKS00013096).}, } @article {pmid38671062, year = {2024}, author = {Angrick, M and Luo, S and Rabbani, Q and Candrea, DN and Shah, S and Milsap, GW and Anderson, WS and Gordon, CR and Rosenblatt, KR and Clawson, L and Tippett, DC and Maragakis, N and Tenore, FV and Fifer, MS and Hermansky, H and Ramsey, NF and Crone, NE}, title = {Online speech synthesis using a chronically implanted brain-computer interface in an individual with ALS.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {9617}, pmid = {38671062}, issn = {2045-2322}, support = {UH3 NS114439/NS/NINDS NIH HHS/United States ; NS114439/NS/NINDS NIH HHS/United States ; }, mesh = {Humans ; *Brain-Computer Interfaces ; *Amyotrophic Lateral Sclerosis/physiopathology/therapy ; Male ; *Speech/physiology ; Middle Aged ; Electrodes, Implanted ; Electrocorticography ; }, abstract = {Brain-computer interfaces (BCIs) that reconstruct and synthesize speech using brain activity recorded with intracranial electrodes may pave the way toward novel communication interfaces for people who have lost their ability to speak, or who are at high risk of losing this ability, due to neurological disorders. Here, we report online synthesis of intelligible words using a chronically implanted brain-computer interface (BCI) in a man with impaired articulation due to ALS, participating in a clinical trial (ClinicalTrials.gov, NCT03567213) exploring different strategies for BCI communication. The 3-stage approach reported here relies on recurrent neural networks to identify, decode and synthesize speech from electrocorticographic (ECoG) signals acquired across motor, premotor and somatosensory cortices. We demonstrate a reliable BCI that synthesizes commands freely chosen and spoken by the participant from a vocabulary of 6 keywords previously used for decoding commands to control a communication board. Evaluation of the intelligibility of the synthesized speech indicates that 80% of the words can be correctly recognized by human listeners. Our results show that a speech-impaired individual with ALS can use a chronically implanted BCI to reliably produce synthesized words while preserving the participant's voice profile, and provide further evidence for the stability of ECoG for speech-based BCIs.}, } @article {pmid38670927, year = {2024}, author = {Quinn, C and Baer, M and Amado, DA and Kelley, M and Elman, L}, title = {A single ALS center experience with clinical use of sodium phenylbutyrate-taurursodiol.}, journal = {Muscle & nerve}, volume = {70}, number = {1}, pages = {148-151}, doi = {10.1002/mus.28096}, pmid = {38670927}, issn = {1097-4598}, mesh = {Humans ; Male ; Female ; *Amyotrophic Lateral Sclerosis/drug therapy ; Middle Aged ; Aged ; Phenylbutyrates/therapeutic use ; Adult ; Retrospective Studies ; Drug Combinations ; }, abstract = {INTRODUCTION/AIMS: The aim of this study was to examine clinical utilization and discontinuation rates of sodium phenylbutyrate-taurursodiol (PB-TURSO) in a single Amyotrophic Lateral Sclerosis (ALS) center. PB-TURSO was approved by the United States Food and Drug Administration (FDA) in September 2022. Prior experience has been limited to clinical trials or expanded access protocols. In this manuscript, we discuss insurance approval rates, patient uptake, and discontinuation of PB-TURSO in a large academic center.

METHODS: Records of patients seen for clinical visits between January 2022 and May 2023 were reviewed. Demographic and clinical characteristics of our clinic population and those initiating PB-TURSO were obtained from our clinical database.

RESULTS: A total of 228 patients were seen during the observation period and 122 requested PB-TURSO prescriptions. 77% (94) were approved by insurance. 66% (65) of those who were approved or received free drug chose to start medication. 51% (34) of those who initiated PB-TURSO continued to take it through the end of the observation period. Four patients discontinued due to death during the observation period. Of the 29 patients who survived and discontinued, the main reasons for discontinuation were GI symptoms (17, 58.6%) and taste (8, 29.6%).

DISCUSSION: PB-TURSO was approved by insurance for most patients. The discontinuation rate was high and was driven largely by GI side effects and taste. Future considerations would include deeper examination of demographic trends, patient costs, side effects, and potential benefits in clinical practice.}, } @article {pmid38670433, year = {2024}, author = {Sitruk-Ware, R and Sussman, H and Brinton, R and Schumacher, M and Singer, P and Kumar, N and De Nicola, AF and El-Etr, M and Guennoun, R and V Borlongan, C}, title = {Nestorone (segesterone acetate) effects on neuroregeneration.}, journal = {Frontiers in neuroendocrinology}, volume = {73}, number = {}, pages = {101136}, doi = {10.1016/j.yfrne.2024.101136}, pmid = {38670433}, issn = {1095-6808}, mesh = {Animals ; Humans ; *Norprogesterones/pharmacology ; *Neuroprotective Agents/pharmacology ; Nerve Regeneration/drug effects/physiology ; Female ; }, abstract = {Nestorone® (segesterone acetate) is a progestin with a chemical structure closely related to progesterone with high affinity and selectivity for the progesterone receptor without significant interaction with other steroid receptors. It has been developed for female and male contraception and is FDA-approved in a first long-acting contraceptive vaginal system for female contraception. Its safety has been extensively demonstrated in both preclinical and clinical studies for contraceptive indications. Nestorone was found to display neuroprotective and neuroregenerative activity in animal models of various central nervous system diseases, including multiple sclerosis, stroke, and amyotrophic lateral sclerosis. Reviewed herein are neuroprotective and myelin- regenerating properties of Nestorone in various animal models and its translational potential as a therapeutic agent for debilitating neurological diseases for which limited therapeutic options are available (Table 1).}, } @article {pmid38668754, year = {2024}, author = {Dogan, M and Teralı, K and Eroz, R and Kılıç, H and Gezdirici, A and Gönüllü, B}, title = {Discovery of a novel homozygous SOD1 truncating variant bolsters infantile SOD1 deficiency syndrome.}, journal = {Molecular biology reports}, volume = {51}, number = {1}, pages = {580}, pmid = {38668754}, issn = {1573-4978}, mesh = {Child ; Female ; Humans ; Male ; *Amyotrophic Lateral Sclerosis/genetics ; Exome Sequencing ; Homozygote ; Pedigree ; Phenotype ; *Superoxide Dismutase-1/genetics ; Turkey ; Adolescent ; }, abstract = {OBJECTIVE: Superoxide dismutase 1 (SOD1) is an important antioxidant enzyme whose main function is to neutralise superoxide free radicals in the cytoplasm. Heterozygous variants in SOD1 are responsible for a substantial percentage of familial amyotrophic lateral sclerosis (ALS) cases. Recently, several reports have shown that biallelic loss of SOD1 function results in a novel phenotype called infantile SOD1 deficiency syndrome, which is consistent with a recessive pattern of inheritance and can be distinguished from typical (adult-onset) ALS.

METHODS: We documented detailed family histories and clinical data, followed by whole-exome sequencing and family co-segregation analysis through Sanger sequencing. To facilitate comparisons, relevant data from fifteen previously reported patients with SOD1-related neurodevelopmental disorders were included.

RESULTS: This study presents a new Turkish family with two affected children exhibiting severe delayed motor development, infancy-onset loss of motor skills, axial hypotonia, tetraspasticity, and impaired cognitive functions. Genetic analysis revealed a novel homozygous frameshift variant in SOD1 (c.248dupG [p.Asp84Argfs*8]), with computational biochemical studies shedding light on the mechanistic aspects of SOD1 dysfunction.

CONCLUSIONS: Our findings contribute an affirmative report of a fourth biallelic variant resulting in a severe clinical phenotype, reminiscent of those induced by previously identified homozygous loss-of-function SOD1 variants. This research not only advances our understanding of the pathogenesis of this debilitating neurological syndrome but also aligns with ongoing intensive efforts to comprehend and address SOD1-linked ALS.}, } @article {pmid38667292, year = {2024}, author = {Ruffo, P and De Amicis, F and La Bella, V and Conforti, FL}, title = {Investigating Repeat Expansions in NIPA1, NOP56, and NOTCH2NLC Genes: A Closer Look at Amyotrophic Lateral Sclerosis Patients from Southern Italy.}, journal = {Cells}, volume = {13}, number = {8}, pages = {}, pmid = {38667292}, issn = {2073-4409}, support = {ex60%//Ministry for Instruction, University and Research/ ; }, mesh = {Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; *Amyotrophic Lateral Sclerosis/genetics ; Case-Control Studies ; DNA Repeat Expansion/genetics ; Genetic Predisposition to Disease ; Italy ; Nuclear Proteins/genetics ; }, abstract = {The discovery of hexanucleotide repeats expansion (RE) in Chromosome 9 Open Reading frame 72 (C9orf72) as the major genetic cause of amyotrophic lateral sclerosis (ALS) and the association between intermediate repeats in Ataxin-2 (ATXN2) with the disorder suggest that repetitive sequences in the human genome play a significant role in ALS pathophysiology. Investigating the frequency of repeat expansions in ALS in different populations and ethnic groups is therefore of great importance. Based on these premises, this study aimed to define the frequency of REs in the NIPA1, NOP56, and NOTCH2NLC genes and the possible associations between phenotypes and the size of REs in the Italian population. Using repeat-primed-PCR and PCR-fragment analyses, we screened 302 El-Escorial-diagnosed ALS patients and compared the RE distribution to 167 age-, gender-, and ethnicity-matched healthy controls. While the REs distribution was similar between the ALS and control groups, a moderate association was observed between longer RE lengths and clinical features such as age at onset, gender, site of onset, and family history. In conclusion, this is the first study to screen ALS patients from southern Italy for REs in NIPA1, NOP56, and NOTCH2NLC genes, contributing to our understanding of ALS genetics. Our results highlighted that the extremely rare pathogenic REs in these genes do not allow an association with the disease.}, } @article {pmid38667285, year = {2024}, author = {Alzahrani, FA and Riza, YM and Eid, TM and Almotairi, R and Scherschinski, L and Contreras, J and Nadeem, M and Perez, SE and Raikwar, SP and Jha, RM and Preul, MC and Ducruet, AF and Lawton, MT and Bhatia, K and Akhter, N and Ahmad, S}, title = {Exosomes in Vascular/Neurological Disorders and the Road Ahead.}, journal = {Cells}, volume = {13}, number = {8}, pages = {}, pmid = {38667285}, issn = {2073-4409}, mesh = {*Exosomes/metabolism ; Humans ; Animals ; Neurodegenerative Diseases/metabolism/pathology ; Vascular Diseases/metabolism/pathology ; Nervous System Diseases/metabolism/pathology ; }, abstract = {Neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), stroke, and aneurysms, are characterized by the abnormal accumulation and aggregation of disease-causing proteins in the brain and spinal cord. Recent research suggests that proteins linked to these conditions can be secreted and transferred among cells using exosomes. The transmission of abnormal protein buildup and the gradual degeneration in the brains of impacted individuals might be supported by these exosomes. Furthermore, it has been reported that neuroprotective functions can also be attributed to exosomes in neurodegenerative diseases. The potential neuroprotective functions may play a role in preventing the formation of aggregates and abnormal accumulation of proteins associated with the disease. The present review summarizes the roles of exosomes in neurodegenerative diseases as well as elucidating their therapeutic potential in AD, PD, ALS, HD, stroke, and aneurysms. By elucidating these two aspects of exosomes, valuable insights into potential therapeutic targets for treating neurodegenerative diseases may be provided.}, } @article {pmid38666827, year = {2024}, author = {Ismail, M and Großmann, D and Hermann, A}, title = {Increased Vulnerability to Ferroptosis in FUS-ALS.}, journal = {Biology}, volume = {13}, number = {4}, pages = {}, pmid = {38666827}, issn = {2079-7737}, support = {NA//Hermann und Lilly Schilling-Stiftung/ ; }, abstract = {Ferroptosis, a regulated form of cell death characterized by iron-dependent lipid peroxide accumulation, plays a pivotal role in various pathological conditions, including neurodegenerative diseases. While reasonable evidence for ferroptosis exists, e.g., in Parkinson's disease or Alzheimer's disease, there are only a few reports on amyotrophic lateral sclerosis (ALS), a fast progressive and incurable neurodegenerative disease characterized by progressive motor neuron degeneration. Interestingly, initial studies have suggested that ferroptosis might be significantly involved in ALS. Key features of ferroptosis include oxidative stress, glutathione depletion, and alterations in mitochondrial morphology and function, mediated by proteins such as GPX4, xCT, ACSL4 FSP1, Nrf2, and TfR1. Induction of ferroptosis involves small molecule compounds like erastin and RSL3, which disrupt system Xc[-] and GPX4 activity, respectively, resulting in lipid peroxidation and cellular demise. Mutations in fused in sarcoma (FUS) are associated with familial ALS. Pathophysiological hallmarks of FUS-ALS involve mitochondrial dysfunction and oxidative damage, implicating ferroptosis as a putative cell-death pathway in motor neuron demise. However, a mechanistic understanding of ferroptosis in ALS, particularly FUS-ALS, remains limited. Here, we investigated the vulnerability to ferroptosis in FUS-ALS cell models, revealing mitochondrial disturbances and increased susceptibility to ferroptosis in cells harboring ALS-causing FUS mutations. This was accompanied by an altered expression of ferroptosis-associated proteins, particularly by a reduction in xCT expression, leading to cellular imbalance in the redox system and increased lipid peroxidation. Iron chelation with deferoxamine, as well as inhibition of the mitochondrial calcium uniporter (MCU), significantly alleviated ferroptotic cell death and lipid peroxidation. These findings suggest a link between ferroptosis and FUS-ALS, offering potential new therapeutic targets.}, } @article {pmid38666665, year = {2024}, author = {Forsberg, K and Karlsborg, M and Salvesen, L and Svenstrup, K and Winroth, I and Berntsson, H and M Andersen, P}, title = {[SOD1 gene therapy delays ALS disease progression].}, journal = {Lakartidningen}, volume = {121}, number = {}, pages = {}, pmid = {38666665}, issn = {1652-7518}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/drug therapy/therapy ; *Superoxide Dismutase-1/genetics ; *Genetic Therapy ; *Disease Progression ; Male ; Middle Aged ; Mutation ; Oligonucleotides, Antisense/therapeutic use/administration & dosage ; Oligonucleotides/therapeutic use/administration & dosage ; }, abstract = {We present a patient with familial amyotrophic lateral sclerosis caused by an aggressive A4S mutation in the SOD1 gene. In 2020, the patient was enrolled in the VALOR SOD1 gene therapy phase-3 trial. At screening, the ALSFRS-R score was 41 (48 is normal) and the level of CSF-neurofilament L (an indicator of ongoing neuronal damage) was 11 000 ng/L (ref <650 ng/L). In the four years following enrollment, the patient received monthly intrathecal treatment with tofersen, an antisense oligonucleotide compound that inhibits SOD1 protein expression and hence lowers the synthesis of toxic SOD1 protein species. Side effects have been minimal and mostly attributed to the spinal taps. The patient remains ambulatory with an active social lifestyle. The ALSFRS-R score has in the past 18 months stabilized around 35-37, CSF-NfL is 1 290 ng/L and plasma-NfL is 12 (reference <13). This is the first documented arresting intervention in a patient with ALS in Sweden.}, } @article {pmid38666601, year = {2024}, author = {Officer, L and Armon, C and Barkhaus, P and Beauchamp, M and Benatar, M and Bertorini, T and Bowser, R and Bromberg, M and Brown, A and Carbunar, OM and Carter, GT and Crayle, J and Denson, K and Feldman, E and Fullam, T and Heiman-Patterson, T and Jackson, C and Jhooty, S and Levinson, D and Li, X and Linares, A and Mallon, E and Mascias Cadavid, J and Mcdermott, C and Mushannen, T and Ostrow, L and Patel, R and Pattee, G and Ratner, D and Sun, Y and Sladky, J and Wicks, P and Bedlack, R}, title = {ALSUntangled #75: Portable neuromodulation stimulator therapy.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {25}, number = {5-6}, pages = {648-652}, doi = {10.1080/21678421.2024.2346825}, pmid = {38666601}, issn = {2167-9223}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy ; *Electric Stimulation Therapy/methods/instrumentation ; }, abstract = {Spurred by patient interest, ALSUntangled herein examines the potential of the Portable Neuromodulation Stimulator (PoNS™) in treating amyotrophic lateral sclerosis (ALS). The PoNS™ device, FDA-approved for the treatment of gait deficits in adult patients with multiple sclerosis, utilizes translingual neurostimulation to stimulate trigeminal and facial nerves via the tongue, aiming to induce neuroplastic changes. While there are early, promising data for PoNS treatment to improve gait and balance in multiple sclerosis, stroke, and traumatic brain injury, no pre-clinical or clinical studies have been performed in ALS. Although reasonably safe, high costs and prescription requirements will limit PoNS accessibility. At this time, due to the lack of ALS-relevant data, we cannot endorse the use of PoNS as an ALS treatment.}, } @article {pmid38665232, year = {2024}, author = {Yao, Y and Liu, H and Gu, Y and Xu, X and Zhang, X}, title = {A causal association between amyotrophic lateral sclerosis and atrial fibrillation: a two-sample Mendelian randomization study.}, journal = {Frontiers in cardiovascular medicine}, volume = {11}, number = {}, pages = {1351495}, pmid = {38665232}, issn = {2297-055X}, abstract = {OBJECTIVES: To look into the connection between amyotrophic lateral sclerosis (ALS) and atrial fibrillation (AF) using Mendelian randomization (MR).

METHODS: Two-sample MR was performed using genetic information from genome-wide association studies (GWAS). Genetic variants robustly associated with ALS and AF were used as instrumental variables. GWAS genetic data for ALS (n = 138,086, ncase = 27,205) and AF (n = 1,030,836, ncase = 60,620), publicly available from IEU Open. The specific MR protocols were Inverse variance-weighted (IVW), Simple mode, MR Egger, Weighted mode, and Weight median estimator (WME). Subsequently, the MR-Egger intercept and Cochran Q examine were used to evaluate instrumental variables (IVs)' heterogeneity and multiplicative effects (IVs). In addition, MR-PRESSO analysis was conducted to exclude any potential pleiotropy.

RESULTS: The IVW method demonstrated that ALS positively affected AF [OR: 1.062, 95% CI (1.004-1.122); P = 0.035]. Indeed, other MR methods were in accordance with the tendency of the IVW method (all OR > 1), and sensitivity testing verified the reliability of this MR result.

CONCLUSIONS: This MR study proves a positive causal connection between ALS and atrial fibrillation. Further studies are warranted to elucidate the mechanisms linking ALS and AF.}, } @article {pmid38664831, year = {2024}, author = {Sirtori, R and J Gregoire, M and M Potts, E and Collins, A and Donatelli, L and Fallini, C}, title = {LINC complex alterations are a key feature of sporadic and familial ALS/FTD.}, journal = {Acta neuropathologica communications}, volume = {12}, number = {1}, pages = {69}, pmid = {38664831}, issn = {2051-5960}, support = {P20 GM103430/GM/NIGMS NIH HHS/United States ; R01 NS116143/NS/NINDS NIH HHS/United States ; R01NS116143/NS/NINDS NIH HHS/United States ; P20GM103430/GM/NIGMS NIH HHS/United States ; }, mesh = {*Amyotrophic Lateral Sclerosis/genetics/pathology/metabolism ; Humans ; *C9orf72 Protein/genetics/metabolism ; *Frontotemporal Dementia/genetics/pathology/metabolism ; Male ; Motor Neurons/pathology/metabolism ; Spinal Cord/pathology/metabolism ; Nuclear Envelope/metabolism/pathology ; Female ; Induced Pluripotent Stem Cells/metabolism/pathology ; Middle Aged ; Aged ; Motor Cortex/pathology/metabolism ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder that primarily affects motor neurons, leading to progressive muscle weakness and loss of voluntary muscle control. While the exact cause of ALS is not fully understood, emerging research suggests that dysfunction of the nuclear envelope (NE) may contribute to disease pathogenesis and progression. The NE plays a role in ALS through several mechanisms, including nuclear pore defects, nucleocytoplasmic transport impairment, accumulation of mislocalized proteins, and nuclear morphology abnormalities. The LINC complex is the second biggest multi-protein complex in the NE and consists of the SUN1/2 proteins spanning the inner nuclear membrane and Nesprin proteins embedded in the outer membrane. The LINC complex, by interacting with both the nuclear lamina and the cytoskeleton, transmits mechanical forces to the nucleus regulating its morphology and functional homeostasis. In this study we show extensive alterations to the LINC complex in motor and cortical iPSC-derived neurons and spinal cord organoids carrying the ALS causative mutation in the C9ORF72 gene (C9). Importantly, we show that such alterations are present in vivo in a cohort of sporadic ALS and C9-ALS postmortem spinal cord and motor cortex specimens. We also found that LINC complex disruption strongly correlated with nuclear morphological alterations occurring in ALS neurons, independently of TDP43 mislocalization. Altogether, our data establish morphological and functional alterations to the LINC complex as important events in ALS pathogenic cascade, making this pathway a possible target for both biomarker and therapy development.}, } @article {pmid38664109, year = {2024}, author = {Hastings, RL and Valdez, G}, title = {Origin, identity, and function of terminal Schwann cells.}, journal = {Trends in neurosciences}, volume = {47}, number = {6}, pages = {432-446}, pmid = {38664109}, issn = {1878-108X}, support = {R56 AG077814/AG/NIA NIH HHS/United States ; R01 AG055545/AG/NIA NIH HHS/United States ; T32 AG041688/AG/NIA NIH HHS/United States ; R56 AG051501/AG/NIA NIH HHS/United States ; R21 NS106313/NS/NINDS NIH HHS/United States ; }, mesh = {*Schwann Cells/physiology ; Animals ; Humans ; }, abstract = {The highly specialized nonmyelinating glial cells present at somatic peripheral nerve endings, known collectively as terminal Schwann cells (TSCs), play critical roles in the development, function and repair of their motor and sensory axon terminals and innervating tissue. Over the past decades, research efforts across various vertebrate species have revealed that while TSCs are a diverse group of cells, they share a number of features among them. In this review, we summarize the state-of-knowledge about each TSC type and explore the opportunities that TSCs provide to treat conditions that afflict peripheral axon terminals.}, } @article {pmid38663103, year = {2024}, author = {Nozal, V and Fernández-Gómez, P and García-Rubia, A and Martínez-González, L and Cuevas, EP and Carro, E and Palomo, V and Martínez, A}, title = {Designing multitarget ligands for neurodegenerative diseases with improved permeability trough PLGA nanoencapsulation.}, journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie}, volume = {175}, number = {}, pages = {116626}, doi = {10.1016/j.biopha.2024.116626}, pmid = {38663103}, issn = {1950-6007}, mesh = {*Polylactic Acid-Polyglycolic Acid Copolymer/chemistry ; Ligands ; Humans ; *Blood-Brain Barrier/metabolism/drug effects ; *Neurodegenerative Diseases/drug therapy/metabolism ; *Permeability ; Nanoparticles/chemistry ; Drug Design ; Drug Compounding ; Amyloid beta-Peptides/metabolism ; Animals ; tau Proteins/metabolism ; }, abstract = {Multitarget ligands (MTLs) have emerged as an interesting alternative for addressing complex multifactorial pathologies such as neurodegenerative diseases. However, a common challenge associated with these compounds is often their high molecular weight and low solubility, which becomes a hurdle when trying to permeate over the blood-brain barrier (BBB). In this study, we have designed two new MTLs that modulate three pharmacological targets simultaneously (tau, beta-amyloid and TAR DNA-binding protein 43). To enhance their brain penetration, we have formulated organic polymeric nanoparticles using poly(lactic-co-glycolic acid). The characterization of the formulations, evaluation of their permeability through an in vitro BBB model, and assessment of their activity on disease-representative cellular models, such as Alzheimer's disease and amyotrophic lateral sclerosis, have been conducted. The results demonstrate the potential of the new MTLs and their nanoparticle encapsulation for the treatment of neurodegenerative diseases.}, } @article {pmid38663099, year = {2024}, author = {Polverino, A and Troisi Lopez, E and Liparoti, M and Minino, R and Romano, A and Cipriano, L and Trojsi, F and Jirsa, V and Sorrentino, G and Sorrentino, P}, title = {Altered spreading of fast aperiodic brain waves relates to disease duration in Amyotrophic Lateral Sclerosis.}, journal = {Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology}, volume = {163}, number = {}, pages = {14-21}, doi = {10.1016/j.clinph.2024.04.003}, pmid = {38663099}, issn = {1872-8952}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology/diagnosis ; Female ; Male ; Middle Aged ; *Magnetoencephalography/methods ; Aged ; Adult ; Brain Waves/physiology ; Brain/physiopathology ; }, abstract = {OBJECTIVE: To test the hypothesis that patients affected by Amyotrophic Lateral Sclerosis (ALS) show an altered spatio-temporal spreading of neuronal avalanches in the brain, and that this may related to the clinical picture.

METHODS: We obtained the source-reconstructed magnetoencephalography (MEG) signals from thirty-six ALS patients and forty-two healthy controls. Then, we used the construct of the avalanche transition matrix (ATM) and the corresponding network parameter nodal strength to quantify the changes in each region, since this parameter provides key information about which brain regions are mostly involved in the spreading avalanches.

RESULTS: ALS patients presented higher values of the nodal strength in both cortical and sub-cortical brain areas. This parameter correlated directly with disease duration.

CONCLUSIONS: In this work, we provide a deeper characterization of neuronal avalanches propagation in ALS, describing their spatio-temporal trajectories and identifying the brain regions most likely to be involved in the process. This makes it possible to recognize the brain areas that take part in the pathogenic mechanisms of ALS. Furthermore, the nodal strength of the involved regions correlates directly with disease duration.

SIGNIFICANCE: Our results corroborate the clinical relevance of aperiodic, fast large-scale brain activity as a biomarker of microscopic changes induced by neurophysiological processes.}, } @article {pmid38663088, year = {2024}, author = {Frost, B and Dubnau, J}, title = {The Role of Retrotransposons and Endogenous Retroviruses in Age-Dependent Neurodegenerative Disorders.}, journal = {Annual review of neuroscience}, volume = {47}, number = {1}, pages = {123-143}, doi = {10.1146/annurev-neuro-082823-020615}, pmid = {38663088}, issn = {1545-4126}, support = {RF1 NS112391/NS/NINDS NIH HHS/United States ; }, mesh = {Humans ; *Neurodegenerative Diseases/genetics ; *Retroelements/genetics ; *Endogenous Retroviruses/genetics ; Animals ; *Aging/genetics ; DNA-Binding Proteins/genetics/metabolism ; tau Proteins/genetics/metabolism ; }, abstract = {Over 40% of the human genome is composed of retrotransposons, DNA species that hold the potential to replicate via an RNA intermediate and are evolutionarily related to retroviruses. Retrotransposons are most studied for their ability to jump within a genome, which can cause DNA damage and novel insertional mutations. Retrotransposon-encoded products, including viral-like proteins, double-stranded RNAs, and extrachromosomal circular DNAs, can also be potent activators of the innate immune system. A growing body of evidence suggests that retrotransposons are activated in age-related neurodegenerative disorders and that such activation causally contributes to neurotoxicity. Here we provide an overview of retrotransposon biology and outline evidence of retrotransposon activation in age-related neurodegenerative disorders, with an emphasis on those involving TAR-DNA binding protein-43 (TDP-43) and tau. Studies to date provide the basis for ongoing clinical trials and hold promise for innovative strategies to ameliorate the adverse effects of retrotransposon dysregulation in neurodegenerative disorders.}, } @article {pmid38662803, year = {2025}, author = {Martín-Rivada, Á and Martos-Moreno, GÁ and Guerra-Cantera, S and Campillo-Calatayud, A and Oxvig, C and Frystyk, J and Chowen, JA and Barrios, V and Argente, J}, title = {Prepubertal Children With Obesity Have High Free IGF-1 Levels and Accelerated Growth Despite Reduced Pappalysin Levels.}, journal = {The Journal of clinical endocrinology and metabolism}, volume = {110}, number = {3}, pages = {e622-e629}, doi = {10.1210/clinem/dgae288}, pmid = {38662803}, issn = {1945-7197}, support = {FIS-PI19/00166//Spanish Ministry of Health/ ; //Centro de Investigación Biomédica en Red Fisiopatología de Obesidad y Nutrición/ ; //Instituto Carlos III/ ; no. CD19/00008//Instituto de Salud Carlos III/ ; //Comunidad Autónoma de Madrid/ ; }, mesh = {Humans ; Male ; Female ; Child ; *Insulin-Like Growth Factor I/metabolism/analysis ; *Pediatric Obesity/blood/physiopathology ; *Pregnancy-Associated Plasma Protein-A/metabolism/analysis ; Glycoproteins/blood ; Intercellular Signaling Peptides and Proteins/blood ; Weight Loss/physiology ; Child, Preschool ; Body Mass Index ; }, abstract = {BACKGROUND: Prepubertal children with obesity frequently have enhanced growth, accelerated skeletal maturation, and changes in the growth hormone-insulin-like growth factor (GH-IGF) axis. However, the involvement of pappalysins (PAPP-A, PAPP-A2) and stanniocalcins (STC1, STC2) as regulators of IGF bioavailability has not been studied in obesity.

OBJECTIVE: We aimed to determine the effects of childhood obesity and weight reduction on serum levels of PAPP-A, PAPP-A2, STC1, and STC2 and their relationship with IGF bioavailability, growth, and other components of the GH-IGF system.

METHODS: Prepubertal children with severe obesity (150, 50% males/females, age: 7.72 ± 2.05 years, BMI z-score: 4.95 ± 1.70, height z-score: 1.28 ± 1.04) were studied at diagnosis and after a minimum of 0.5 BMI z-score reduction. Two hundred and six healthy age- and sex-matched children were used as controls.

RESULTS: Children with obesity had decreased serum concentrations of PAPP-A, PAPP-A2 and STC2, but increased total and free IGF-I, intact IGFBP-3, acid-labile subunit (ALS), IGF-II, and insulin levels, with no difference in the free IGF-I/total IGF-I ratio. Neither the standardized body mass index (BMI) nor height correlated with any biochemical parameter analyzed. A decrease in IGF-II, insulin, and ALS with an increase in IGFBP-2 and -5, STC2, and PAPP-A were observed after weight loss.

CONCLUSION: Increased circulating total and free IGF-I, insulin, and IGF-II may all contribute to the increased rate of prepubertal growth and bone maturation observed in children with obesity, with STC2 possibly being involved.}, } @article {pmid38662766, year = {2024}, author = {Stikvoort García, DJL and Goedee, HS and van Eijk, RPA and van Schelven, LJ and van den Berg, LH and Sleutjes, BTHM}, title = {Revisiting distinct nerve excitability patterns in patients with amyotrophic lateral sclerosis.}, journal = {Brain : a journal of neurology}, volume = {147}, number = {8}, pages = {2842-2853}, pmid = {38662766}, issn = {1460-2156}, support = {AV20180012//Dutch ALS Foundation/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/physiopathology ; Humans ; Male ; Female ; Middle Aged ; Aged ; *Motor Neurons/physiology ; Adult ; Action Potentials/physiology ; Principal Component Analysis ; Axons/physiology ; Membrane Potentials/physiology ; }, abstract = {Amyotrophic lateral sclerosis is a devastating neurodegenerative disease, characterized by loss of central and peripheral motor neurons. Although the disease is clinically and genetically heterogeneous, axonal hyperexcitability is a commonly observed feature that has been suggested to reflect an early pathophysiological step linked to the neurodegenerative cascade. Therefore, it is important to clarify the mechanisms causing axonal hyperexcitability and how these relate to the clinical characteristics of patients. Measures derived directly from a nerve excitability recording are frequently used as study end points, although their biophysical basis is difficult to deduce. Mathematical models can aid in the interpretation but are reliable only when applied to group-averaged recordings. Consequently, model estimates of membrane properties cannot be compared with clinical characteristics or treatment effects in individual patients, posing a considerable limitation in heterogeneous diseases, such as amyotrophic lateral sclerosis. To address these challenges, we revisited nerve excitability using a new pattern analysis-based approach (principal component analysis). We evaluated disease-specific patterns of excitability changes and established their biophysical origins. Based on the observed patterns, we developed new compound measures of excitability that facilitate the implementation of this approach in clinical settings. We found that excitability changes in amyotrophic lateral sclerosis patients (n = 161, median disease duration = 11 months) were characterized by four unique patterns compared with controls (n = 50, age and sex matched). These four patterns were best explained by changes in resting membrane potential (modulated by Na+/K+ currents), slow potassium and sodium currents (modulated by their gating kinetics) and refractory properties of the nerve. Consequently, we were able to show that altered gating of slow potassium channels was associated with, and predictive of, the rate of progression of the disease on the amyotrophic lateral sclerosis functional rating scale. Based on these findings, we designed four composite measures that capture these properties to facilitate implementation outside this study. Our findings demonstrate that changes in nerve excitability in patients with amyotrophic lateral sclerosis are dominated by four distinct patterns, each with a distinct biophysical origin. Based on this new approach, we provide evidence that altered slow potassium-channel function might play a role in the rate of disease progression. The magnitudes of these patterns, quantified using a similar approach or our new composite measures, have potential as efficient measures to study membrane properties directly in amyotrophic lateral sclerosis patients, and thus aid prognostic stratification and trial design.}, } @article {pmid38661532, year = {2024}, author = {Li, A and Yi, J and Li, X and Dong, L and Ostrow, LW and Ma, J and Zhou, J}, title = {Distinct transcriptomic profile of satellite cells contributes to preservation of neuromuscular junctions in extraocular muscles of ALS mice.}, journal = {eLife}, volume = {12}, number = {}, pages = {}, pmid = {38661532}, issn = {2050-084X}, support = {R01 NS105621/NS/NINDS NIH HHS/United States ; R01 AG071676/AG/NIA NIH HHS/United States ; R01NS105621/NH/NIH HHS/United States ; R01AG071676/NH/NIH HHS/United States ; R01NS129219/NH/NIH HHS/United States ; R01 NS129219/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; *Neuromuscular Junction/metabolism ; *Amyotrophic Lateral Sclerosis/genetics/metabolism ; Mice ; *Satellite Cells, Skeletal Muscle/metabolism ; *Disease Models, Animal ; *Transcriptome ; Mice, Transgenic ; Oculomotor Muscles/innervation/metabolism ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neuromuscular disorder characterized by progressive weakness of almost all skeletal muscles, whereas extraocular muscles (EOMs) are comparatively spared. While hindlimb and diaphragm muscles of end-stage SOD1G93A (G93A) mice (a familial ALS mouse model) exhibit severe denervation and depletion of Pax7[+]satellite cells (SCs), we found that the pool of SCs and the integrity of neuromuscular junctions (NMJs) are maintained in EOMs. In cell sorting profiles, SCs derived from hindlimb and diaphragm muscles of G93A mice exhibit denervation-related activation, whereas SCs from EOMs of G93A mice display spontaneous (non-denervation-related) activation, similar to SCs from wild-type mice. Specifically, cultured EOM SCs contain more abundant transcripts of axon guidance molecules, including Cxcl12, along with more sustainable renewability than the diaphragm and hindlimb counterparts under differentiation pressure. In neuromuscular co-culture assays, AAV-delivery of Cxcl12 to G93A-hindlimb SC-derived myotubes enhances motor neuron axon extension and innervation, recapitulating the innervation capacity of EOM SC-derived myotubes. G93A mice fed with sodium butyrate (NaBu) supplementation exhibited less NMJ loss in hindlimb and diaphragm muscles. Additionally, SCs derived from G93A hindlimb and diaphragm muscles displayed elevated expression of Cxcl12 and improved renewability following NaBu treatment in vitro. Thus, the NaBu-induced transcriptomic changes resembling the patterns of EOM SCs may contribute to the beneficial effects observed in G93A mice. More broadly, the distinct transcriptomic profile of EOM SCs may offer novel therapeutic targets to slow progressive neuromuscular functional decay in ALS and provide possible 'response biomarkers' in pre-clinical and clinical studies.}, } @article {pmid38658168, year = {2024}, author = {Jaroszynska, N and Salzinger, A and Tsarouchas, TM and Becker, CG and Becker, T and Lyons, DA and MacDonald, RB and Keatinge, M}, title = {C9ORF72 Deficiency Results in Neurodegeneration in the Zebrafish Retina.}, journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, volume = {44}, number = {25}, pages = {}, pmid = {38658168}, issn = {1529-2401}, mesh = {Animals ; *Zebrafish ; Female ; *C9orf72 Protein/genetics/metabolism ; *Retina/metabolism/pathology ; Animals, Genetically Modified ; Zebrafish Proteins/genetics/metabolism/deficiency ; Proteins/genetics/metabolism ; Retinal Degeneration/genetics/metabolism/pathology ; Neurodegenerative Diseases/genetics/metabolism/pathology ; Spinal Cord/metabolism/pathology ; }, abstract = {Hexanucleotide repeat expansions within the gene C9ORF72 are the most common cause of the neurodegenerative diseases amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). This disease-causing expansion leads to a reduction in C9ORF72 expression levels in patients, suggesting loss of C9ORF72 function could contribute to disease. To further understand the consequences of C9ORF72 deficiency in vivo, we generated a c9orf72 mutant zebrafish line. Analysis of the adult female spinal cords revealed no appreciable neurodegenerative pathology such as loss of motor neurons or increased levels of neuroinflammation. However, detailed examination of adult female c9orf72[-/-] retinas showed prominent neurodegenerative features, including a decrease in retinal thickness, gliosis, and an overall reduction in neurons of all subtypes. Analysis of rod and cone cells within the photoreceptor layer showed a disturbance in their outer segment structure and rhodopsin mislocalization from rod outer segments to their cell bodies and synaptic terminals. Thus, C9ORF72 may play a previously unappreciated role in retinal homeostasis and suggests C9ORF72 deficiency can induce tissue specific neuronal loss.}, } @article {pmid38657911, year = {2024}, author = {Liguori, F and Alberti, F and Amadio, S and Angelini, DF and Pilesi, E and Vitale, G and Tesoriere, G and Borsellino, G and Vernì, F and Volonté, C}, title = {Pan-neuronal expression of human mutant SOD1 in Drosophila impairs survival and motor performance, induces early neuroinflammation and chromosome aberrations.}, journal = {Biochimica et biophysica acta. Molecular basis of disease}, volume = {1870}, number = {5}, pages = {167192}, doi = {10.1016/j.bbadis.2024.167192}, pmid = {38657911}, issn = {1879-260X}, mesh = {Animals ; *Superoxide Dismutase-1/genetics/metabolism ; Humans ; *Drosophila melanogaster/genetics ; *Amyotrophic Lateral Sclerosis/genetics/pathology/metabolism ; *Animals, Genetically Modified ; *Mutation ; *Chromosome Aberrations ; Drosophila Proteins/genetics/metabolism ; Motor Neurons/metabolism/pathology ; Disease Models, Animal ; Neuroinflammatory Diseases/genetics/metabolism/pathology ; Neurons/metabolism/pathology ; }, abstract = {Several mutations in the SOD1 gene encoding for the antioxidant enzyme Superoxide Dismutase 1, are associated with amyotrophic lateral sclerosis, a rare and devastating disease characterized by motor neuron degeneration and patients' death within 2-5 years from diagnosis. Motor neuron loss and related symptomatology manifest mostly in adult life and, to date, there is still a gap of knowledge on the precise cellular and molecular events preceding neurodegeneration. To deepen our awareness of the early phases of the disease, we leveraged two Drosophila melanogaster models pan-neuronally expressing either the mutation A4V or G85R of the human gene SOD1 (hSOD1[A4V] or hSOD1[G85R]). We demonstrate that pan-neuronal expression of the hSOD1[A4V] or hSOD1[G85R] pathogenic construct impairs survival and motor performance in transgenic flies. Moreover, protein and transcript analysis on fly heads indicates that mutant hSOD1 induction stimulates the glial marker Repo, up-regulates the IMD/Toll immune pathways through antimicrobial peptides and interferes with oxidative metabolism. Finally, cytological analysis of larval brains demonstrates hSOD1-induced chromosome aberrations. Of note, these parameters are found modulated in a timeframe when neurodegeneration is not detected. The novelty of our work is twofold: we have expressed for the first time hSOD1 mutations in all neurons of Drosophila and confirmed some ALS-related pathological phenotypes in these flies, confirming the power of SOD1 mutations in generating ALS-like phenotypes. Moreover, we have related SOD1 pathogenesis to chromosome aberrations and antimicrobial peptides up-regulation. These findings were unexplored in the SOD1-ALS field.}, } @article {pmid38657488, year = {2024}, author = {Rezaee Semnani, M and Mirzaasgari, Z and Ariaei, A and Haghi Ashtiani, B}, title = {Evaluation of carotid Intima-Media Thickness (IMT) in amyotrophic lateral sclerosis disease using ultrasonography.}, journal = {Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia}, volume = {124}, number = {}, pages = {67-72}, doi = {10.1016/j.jocn.2024.04.019}, pmid = {38657488}, issn = {1532-2653}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnostic imaging ; Male ; Female ; *Carotid Intima-Media Thickness ; Middle Aged ; Adult ; Aged ; Ultrasonography/methods ; Body Mass Index ; }, abstract = {BACKGROUND: Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disease with multi-mechanisms as; inflammation, oxidative stress, glutamate excitotoxicity, protein aggregation, etc. This study aimed to evaluate the carotid Intima-Media Thickness (IMT) in ALS and healthy groups, as a possible indicator of these mechanisms.

METHODS: 42 patients with ALS along with 53 normal age and body mass index (BMI) matched participants were recruited from the Firoozgar hospital. Carotid IMT values of the participants were measured using B-mode ultrasonography. Using Pearson correlation and logistic regression adjusting with age, BMI, and gender, the IMT values were assessed.

RESULTS: The mean right and left carotid IMT values of the ALS patients (0.66 ± 0.09) were significantly higher than normal participants (0.45 ± 0.10) (p < 0.001). In addition, the IMT values were highly correlated with the age (r = 0.632; p < 0.001) and the age of ALS onset (r = 0.595; p < 0.001), in contrast to the BMI. Moreover, the higher value of IMT was associated with an increasing risk of ALS with an odd ratio (OR) of 1.483 (95 % Confidence interval [1.026-2.144]). Eventually, evaluating IMT by classifying ALS patients based on the ALS Health State Scale (ALSHSS) from early to late stage revealed a non-linear increase in the OR (1.372, 1.898, 2.172, and 3.403).

CONCLUSION: The increased value of the carotid IMT independent of BMI in ALS could be assessed through ultrasonography as a convenient tool to evaluate the disease severity or possible systemic inflammation.}, } @article {pmid38657132, year = {2025}, author = {Washington, KT and Mechling, CA and Pitzer, KA and Maiser, S and Mehta, AK}, title = {Identifying the Unmet Needs of People Living With Amyotrophic Lateral Sclerosis: A National Survey to Inform Interdisciplinary Palliative Care.}, journal = {The American journal of hospice & palliative care}, volume = {42}, number = {4}, pages = {326-333}, doi = {10.1177/10499091241248653}, pmid = {38657132}, issn = {1938-2715}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/psychology/therapy ; *Palliative Care/organization & administration/psychology ; Male ; Female ; Quality of Life ; Middle Aged ; Aged ; Advance Care Planning/organization & administration ; Adult ; Disease Progression ; Terminal Care/psychology/organization & administration ; Surveys and Questionnaires ; Aged, 80 and over ; *Needs Assessment ; }, abstract = {Introduction/Aims: This national survey builds on previous qualitative research examining potential palliative care needs among people living with ALS (pALS) by quantifying and investigating relationships among pALS' stage of illness progression; physical, emotional, social, spiritual, and intimacy-related concerns; advance care planning behaviors; perceptions of feeling heard and understood by healthcare providers; and overall quality of life. Methods: Researchers partnered with national organizations to recruit pALS to participate in a one-time survey comprising items from validated instruments (eg, the ALS Specific Quality of Life Instrument-Revised) and researcher-generated measures. Data were analyzed using logistic and linear regression. Results: Among pALS (n = 112), many respondents indicated they had discussed their wishes for end-of-life care with family or friends, shared their wishes with providers, and documented their wishes in writing (79.5%, 49.1%, and 63.4%, respectively). Mean (M) quality of life scores were moderate (M ≈ 6 of 10). Illness stage was associated with documentation of end-of-life care wishes but not with having discussed these wishes with others or with overall quality of life. Reported emotional intimacy received was comparable to that desired (difference = .01 of 10); however, a greater desire for physical intimacy relative to that received was indicated (difference = 1.75 of 10). Discussion: Interdisciplinary palliative care teams may enhance ALS care by promoting advance care planning behaviors (particularly discussing one's wishes with healthcare providers), providing interventions to improve quality of life, and supporting pALS in navigating challenges related to physical intimacy.}, } @article {pmid38655803, year = {2024}, author = {Temkin-Greener, H and Hua, Y and Cai, S}, title = {Assisted living residents with dementia: Disparities in mental health services pre and during COVID-19.}, journal = {Journal of the American Geriatrics Society}, volume = {72}, number = {6}, pages = {1760-1769}, pmid = {38655803}, issn = {1532-5415}, support = {RF1 AG063811/AG/NIA NIH HHS/United States ; R01HS026893//Agency for Healthcare Research and Quality/ ; RF1 AG073052/AG/NIA NIH HHS/United States ; RF1AG063811/AG/NIA NIH HHS/United States ; R01 HS026893/HS/AHRQ HHS/United States ; RF1AG073052/AG/NIA NIH HHS/United States ; }, mesh = {Humans ; *COVID-19/epidemiology ; United States/epidemiology ; Male ; Female ; *Assisted Living Facilities/statistics & numerical data ; Aged ; *Telemedicine/statistics & numerical data ; *Dementia/epidemiology/therapy ; *Medicare/statistics & numerical data ; *Mental Health Services/statistics & numerical data ; Aged, 80 and over ; *Healthcare Disparities/statistics & numerical data ; SARS-CoV-2 ; Medicaid/statistics & numerical data ; Health Services Accessibility/statistics & numerical data ; }, abstract = {BACKGROUND: Little is known about mental health among Medicare beneficiaries with Alzheimer's disease or related dementias (ADRD) who reside in assisted living (AL) communities. The COVID-19 pandemic may have curtailed ambulatory care access for these residents, but telehealth may have expanded it. We examined in-person and telehealth use of ambulatory mental health visits among AL residents with ADRD, pre and during the COVID pandemic, focusing on race/ethnicity and Medicare/Medicaid dual status.

METHODS: A CY2018 cohort of AL residents with ADRD was identified. Outcome was any quarterly in-person or telemedicine mental health visit based on national CY2019-2020 Medicare claims. Key independent variables were individual race/ethnicity and dual status and the AL-level proportion of dual residents. We estimated a linear probability model with random effects and robust standard errors. Quarterly indicators captured service use before and after the onset of the pandemic.

RESULTS: The study included 102,758 fee-for-service Medicare beneficiaries with ADRD in 13,400 ALs. One in five residents had any mental health visits prior to the COVID-19 pandemic. Black residents, and those with dual Medicare/Medicaid eligibility, were significantly less likely to use mental health services prior to and during the pandemic. There were no significant differences in visits via telemedicine by race/ethnicity or individual dual status. Residents in AL communities with a higher proportion of duals had a lower likelihood of visits before and during the pandemic.

CONCLUSIONS/IMPLICATIONS: Mental health service use among AL residents with ADRD was low and declining prior to the pandemic. Telehealth allowed for mental health visits to continue during the pandemic, albeit at a lower level. Residents in ALs with a higher proportion of duals were less likely to have in-person or telehealth visits. The results suggest that some ALs may find it difficult to assure mental health service provision to this vulnerable population.}, } @article {pmid38655443, year = {2024}, author = {Zubair, AS and Saab, L and Scharer, K and Khokhar, B}, title = {Patients' experiences with methylcobalamin injections in amyotrophic lateral sclerosis.}, journal = {Brain circulation}, volume = {10}, number = {1}, pages = {60-66}, pmid = {38655443}, issn = {2455-4626}, abstract = {BACKGROUND AND OBJECTIVES: Amyotrophic lateral sclerosis (ALS) is a progressive motor neuron disease with no definitive treatment. Vitamin B12 is not a Food and Drug Administration-approved treatment in the United States, although it has been prescribed off-label as ultra-high-dose methylcobalamin, which has been shown to be safe and effective in slowing functional decline in patients with ALS. This study evaluates the impact of Vitamin B12 injections on the quality of life of five patients.

METHODS: Semi-structured interviews were conducted with the patients and caregivers. The data was carefully read, coded, and organized into themes and sub-themes by two independent researchers.

RESULTS: The study found four themes and 11 subthemes from the data, including initial circumstances, administration of the injection, subjective experience with Vitamin B12, and outcomes and expectations. All participants recognized some benefits from Vitamin B12 injections, specifically increased energy, reduced fatigue, and improved balance. However, some patients had difficulty monitoring its specific effect due to the progressive nature of the disease.

DISCUSSION: The flexibility offered by this intervention is beneficial for patients with declining mobility and strength who wish to adapt their treatment to their schedule. This work is a modest call to fill the existing gap in the literature and push for more randomized controlled trials investigating and clarifying the effects of Vitamin B12 injections on disease progression, muscle function, and quality of life in a small but diverse pool of patients with ALS.}, } @article {pmid38654338, year = {2024}, author = {Li, Y and Hu, Q and Wang, Q and Liu, T and Gao, M}, title = {Real-time ultrasound-guided sacral plexus block combined with mild sedation for hemorrhoidectomy and hemorrhoidal artery ligation in a patient with amyotrophic lateral sclerosis: a case report.}, journal = {Journal of medical case reports}, volume = {18}, number = {1}, pages = {205}, pmid = {38654338}, issn = {1752-1947}, mesh = {Humans ; Female ; Middle Aged ; *Amyotrophic Lateral Sclerosis/complications ; *Ultrasonography, Interventional ; *Hemorrhoidectomy/methods ; Ligation ; *Nerve Block/methods ; *Dexmedetomidine/administration & dosage ; *Lumbosacral Plexus/diagnostic imaging ; Hemorrhoids/surgery ; Hypnotics and Sedatives/administration & dosage ; Treatment Outcome ; }, abstract = {BACKGROUND: Patients with amyotrophic lateral sclerosis present perioperative challenges for clinical anesthesiologists for anesthesia-associated complications.

CASE PRESENTATION: A 54-year-old Han woman with a 2-year history of amyotrophic lateral sclerosis was scheduled for hemorrhoidectomy and hemorrhoidal artery ligation. We performed real-time ultrasound-guided sacral plexus block with dexmedetomidine under standard monitoring. The anesthesia method met the surgical demands and avoided respiratory complications during the procedures. There was no neurological deterioration after the surgery and 3 months after, the patient was discharged.

CONCLUSIONS: Real-time ultrasound-guided sacral plexus block combined with mild sedation may be an effective and safe technique in patients with amyotrophic lateral sclerosis undergoing hemorrhoidectomy and hemorrhoidal artery ligation.}, } @article {pmid38652017, year = {2024}, author = {Rahman, MU and Bano, S and Hong, X and Gu, RX and Chen, HF}, title = {Early Aggregation Mechanism of SOD128-38 Based on Force Field Parameter of 5-Cyano-Tryptophan.}, journal = {Journal of chemical information and modeling}, volume = {64}, number = {9}, pages = {3942-3952}, doi = {10.1021/acs.jcim.4c00289}, pmid = {38652017}, issn = {1549-960X}, mesh = {Humans ; Kinetics ; Markov Chains ; Molecular Dynamics Simulation ; *Protein Aggregates ; Protein Multimerization ; *Superoxide Dismutase-1/chemistry/metabolism ; *Tryptophan/chemistry/metabolism ; }, abstract = {The aggregation of superoxide dismutase 1 (SOD1) results in amyloid deposition and is involved in familial amyotrophic lateral sclerosis, a fatal motor neuron disease. There have been extensive studies of its aggregation mechanism. Noncanonical amino acid 5-cyano-tryptophan (5-CN-Trp), which has been incorporated into the amyloid segments of SOD1 as infrared probes to increase the structural sensitivity of IR spectroscopy, is found to accelerate the overall aggregation rate and potentially modulate the aggregation process. Despite these observations, the underlying mechanism remains elusive. Here, we optimized the force field parameters of 5-CN-Trp and then used molecular dynamics simulation along with the Markov state model on the SOD128-38 dimer to explore the kinetics of key intermediates in the presence and absence of 5-CN-Trp. Our findings indicate a significantly increased probability of protein aggregate formation in 5CN-Trp-modified ensembles compared to wildtype. Dimeric β-sheets of different natures were observed exclusively in the 5CN-Trp-modified peptides, contrasting with wildtype simulations. Free-energy calculations and detailed analyses of the dimer structure revealed augmented interstrand interactions attributed to 5-CN-Trp, which contributed more to peptide affinity than any other residues. These results explored the key events critical for the early nucleation of amyloid-prone proteins and also shed light on the practice of using noncanonical derivatives to study the aggregation mechanism.}, } @article {pmid38648781, year = {2024}, author = {Ikegawa, Y and Fukuma, R and Sugano, H and Oshino, S and Tani, N and Tamura, K and Iimura, Y and Suzuki, H and Yamamoto, S and Fujita, Y and Nishimoto, S and Kishima, H and Yanagisawa, T}, title = {Text and image generation from intracranial electroencephalography using an embedding space for text and images.}, journal = {Journal of neural engineering}, volume = {21}, number = {3}, pages = {}, doi = {10.1088/1741-2552/ad417a}, pmid = {38648781}, issn = {1741-2552}, mesh = {Humans ; *Brain-Computer Interfaces ; Male ; Female ; *Electrocorticography/methods ; Adult ; Electroencephalography/methods ; Middle Aged ; Electrodes, Implanted ; Young Adult ; Photic Stimulation/methods ; }, abstract = {Objective.Invasive brain-computer interfaces (BCIs) are promising communication devices for severely paralyzed patients. Recent advances in intracranial electroencephalography (iEEG) coupled with natural language processing have enhanced communication speed and accuracy. It should be noted that such a speech BCI uses signals from the motor cortex. However, BCIs based on motor cortical activities may experience signal deterioration in users with motor cortical degenerative diseases such as amyotrophic lateral sclerosis. An alternative approach to using iEEG of the motor cortex is necessary to support patients with such conditions.Approach. In this study, a multimodal embedding of text and images was used to decode visual semantic information from iEEG signals of the visual cortex to generate text and images. We used contrastive language-image pretraining (CLIP) embedding to represent images presented to 17 patients implanted with electrodes in the occipital and temporal cortices. A CLIP image vector was inferred from the high-γpower of the iEEG signals recorded while viewing the images.Main results.Text was generated by CLIPCAP from the inferred CLIP vector with better-than-chance accuracy. Then, an image was created from the generated text using StableDiffusion with significant accuracy.Significance.The text and images generated from iEEG through the CLIP embedding vector can be used for improved communication.}, } @article {pmid38647433, year = {2024}, author = {Mousavi, H and Rimaz, M and Zeynizadeh, B}, title = {Practical Three-Component Regioselective Synthesis of Drug-Like 3-Aryl(or heteroaryl)-5,6-dihydrobenzo[h]cinnolines as Potential Non-Covalent Multi-Targeting Inhibitors To Combat Neurodegenerative Diseases.}, journal = {ACS chemical neuroscience}, volume = {15}, number = {9}, pages = {1828-1881}, doi = {10.1021/acschemneuro.4c00055}, pmid = {38647433}, issn = {1948-7193}, mesh = {Humans ; *Neurodegenerative Diseases/drug therapy/metabolism ; *Molecular Docking Simulation/methods ; Neuroprotective Agents/pharmacology/chemical synthesis/chemistry ; Heterocyclic Compounds, 2-Ring/pharmacology/chemical synthesis/chemistry ; Structure-Activity Relationship ; }, abstract = {Neurodegenerative diseases (NDs) are one of the prominent health challenges facing contemporary society, and many efforts have been made to overcome and (or) control it. In this research paper, we described a practical one-pot two-step three-component reaction between 3,4-dihydronaphthalen-1(2H)-one (1), aryl(or heteroaryl)glyoxal monohydrates (2a-h), and hydrazine monohydrate (NH2NH2•H2O) for the regioselective preparation of some 3-aryl(or heteroaryl)-5,6-dihydrobenzo[h]cinnoline derivatives (3a-h). After synthesis and characterization of the mentioned cinnolines (3a-h), the in silico multi-targeting inhibitory properties of these heterocyclic scaffolds have been investigated upon various Homo sapiens-type enzymes, including hMAO-A, hMAO-B, hAChE, hBChE, hBACE-1, hBACE-2, hNQO-1, hNQO-2, hnNOS, hiNOS, hPARP-1, hPARP-2, hLRRK-2[(G2019S)], hGSK-3β, hp38α MAPK, hJNK-3, hOGA, hNMDA receptor, hnSMase-2, hIDO-1, hCOMT, hLIMK-1, hLIMK-2, hRIPK-1, hUCH-L1, hPARK-7, and hDHODH, which have confirmed their functions and roles in the neurodegenerative diseases (NDs), based on molecular docking studies, and the obtained results were compared with a wide range of approved drugs and well-known (with IC50, EC50, etc.) compounds. In addition, in silico ADMET prediction analysis was performed to examine the prospective drug properties of the synthesized heterocyclic compounds (3a-h). The obtained results from the molecular docking studies and ADMET-related data demonstrated that these series of 3-aryl(or heteroaryl)-5,6-dihydrobenzo[h]cinnolines (3a-h), especially hit ones, can really be turned into the potent core of new drugs for the treatment of neurodegenerative diseases (NDs), and/or due to the having some reactionable locations, they are able to have further organic reactions (such as cross-coupling reactions), and expansion of these compounds (for example, with using other types of aryl(or heteroaryl)glyoxal monohydrates) makes a new avenue for designing novel and efficient drugs for this purpose.}, } @article {pmid38647181, year = {2024}, author = {Zejlon, C and Sennfält, S and Finnsson, J and Connolly, B and Petersson, S and Granberg, T and Ingre, C}, title = {Motor band sign is specific for amyotrophic lateral sclerosis and corresponds to motor symptoms.}, journal = {Annals of clinical and translational neurology}, volume = {11}, number = {5}, pages = {1280-1289}, pmid = {38647181}, issn = {2328-9503}, support = {20190565//Region Stockholm and Karolinska Institutet through ALF Medicine/ ; 976444//Region Stockholm and Karolinska Institutet through ALF Medicine/ ; //Neuroförbundet/ ; //Svenska Frimurarorden/ ; //Ulla-Carin Lindquists stiftelse för ALS-forskning/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology/diagnosis/genetics ; Male ; Female ; Middle Aged ; Aged ; *Magnetic Resonance Imaging ; *Motor Cortex/diagnostic imaging/physiopathology ; Prospective Studies ; Adult ; Sensitivity and Specificity ; C9orf72 Protein/genetics ; }, abstract = {OBJECTIVE: Magnetic resonance imaging can detect neurodegenerative iron accumulation in the motor cortex, called the motor band sign. This study aims to evaluate its sensitivity/specificity and correlations to symptomatology, biomarkers, and clinical outcome in amyotrophic lateral sclerosis.

METHODS: This prospective study consecutively enrolled 114 persons with amyotrophic lateral sclerosis and 79 mimics referred to Karolinska University Hospital, and also 31 healthy controls. All underwent 3-Tesla brain susceptibility-weighted imaging. Three raters independently assessed motor cortex susceptibility with total and regional motor band scores. Survival was evaluated at a median of 34.2 months after the imaging.

RESULTS: The motor band sign identified amyotrophic lateral sclerosis with a sensitivity of 59.6% and a specificity of 91.1% versus mimics and 96.8% versus controls. Higher motor band scores were more common with genetic risk factors (p = 0.032), especially with C9orf72 mutation, and were associated with higher neurofilament light levels (std. β 0.22, p = 0.019). Regional scores correlated strongly with focal symptoms (medial region vs. gross motor dysfunction, std. β -0.64, p = 0.001; intermediate region vs. fine motor dysfunction, std. β -0.51, p = 0.031; lateral region vs. bulbar symptoms std. β -0.71, p < 0.001). There were no associations with cognition, progression rate, or survival.

INTERPRETATION: In a real-life clinical setting, the motor band sign has high specificity but relatively low sensitivity for identifying amyotrophic lateral sclerosis. Associations with genetic risk factors, neurofilament levels and somatotopic correspondence to focal motor weakness suggest that the motor band sign could be a suitable biomarker for diagnostics and clinical trials in amyotrophic lateral sclerosis.}, } @article {pmid38646691, year = {2024}, author = {Flynn, MB and Flynn, JF and Palacios, AM}, title = {Capitalizing on Hope: Questionable Marketing Approval and Pricing of a New ALS Drug.}, journal = {International journal of social determinants of health and health services}, volume = {54}, number = {4}, pages = {405-411}, doi = {10.1177/27551938241247778}, pmid = {38646691}, issn = {2755-1946}, mesh = {*Amyotrophic Lateral Sclerosis/drug therapy/economics ; Humans ; *Drug Approval ; United States ; United States Food and Drug Administration ; Cost-Benefit Analysis ; }, abstract = {Regulatory agencies must balance patient demands to access new treatments for fatal diseases with limited treatment options while ensuring drug safety and efficacy. However, questionable U.S. regulatory actions resulted in the early approval of AMX0035 to treat amyotrophic lateral sclerosis (ALS) by reconvening advisory commissions to obtain positive decisions and designating the drug as a new molecular entity. Data from one randomized clinical trial suggests minimal delays in disease progression and longer survivability, but debate remains about the lack of confirmatory evidence of effectiveness owing to study limitations. A patient's decision-making process details the experience of using the drug, including perspectives on access, cost, effectiveness, and adverse effects. In line with the "nichebuster" business model, the drugmaker, Amylyx Pharmaceuticals, is charging US$158,000/year/patient and thus forecast to turn a profit on a drug with debatable clinical effectiveness prior to completing a Phase 3 trial. Early marketing approval, despite community demands, is unnecessary and may have reduced access because of the end of a compassionate use program, and the high price tag results in restricted coverage and high out-of-pocket costs. Also, the drug's key ingredients are available as a generic and a supplement.}, } @article {pmid38646235, year = {2024}, author = {Hagino, T and Ochiai, S and Hagino, T and Furuya, N and Wako, M and Haro, H}, title = {Impacts of Segond Fractures on Anterior Cruciate Ligament Reconstruction Outcomes.}, journal = {Cureus}, volume = {16}, number = {3}, pages = {e56542}, pmid = {38646235}, issn = {2168-8184}, abstract = {INTRODUCTION: Segond fractures, characterized by avulsion injuries at the lateral tibial condyle's anterolateral structure (ALS) attachment, often coincide with anterior cruciate ligament (ACL) injuries, potentially leading to knee instability. However, the influence of Segond fractures on knee stability after ACL reconstruction remains uncertain. Despite documented ALS reconstructions, there is a lack of consensus regarding the assessment of ALS failure and the criteria for surgical interventions. This study aimed to determine if Segond fracture presence impacts ACL reconstruction outcomes, utilizing patient-reported subjective assessments and healthcare providers' objective evaluations.

MATERIALS AND METHODS: This retrospective study encompassed 639 patients (328 males, 311 females; mean age 26.9 years) who underwent ACL reconstruction, with a follow-up of at least one year. Subjects were divided into two groups: Segond fractures diagnosed through radiographic findings (Group S+, n = 17) and no Segond fractures (Group S-, n = 622). Clinical evaluation included the 36-item Short Form Survey (SF-36), Lysholm score, visual analog scale (VAS) for knee pain, knee injury and osteoarthritis outcome score (KOOS), and knee instability assessment via Telos SE (Telos Japan, Tokyo, Japan). Statistical comparisons were performed between the two groups.

RESULTS: At the final follow-up, all SF-36 subscales improved in all eight subscales compared to before surgery, reaching national standard scores; no significant inter-group differences were evident. Lysholm scores were 93.0 ± 12.1 (Group S+) and 91.7 ± 10.9 (Group S-) (P = 0.62), VAS for knee pain was 10.0 ± 18.0 (Group S+) and 11.9 ± 16.9 (Group S-) (P = 0.62), total KOOS was 89.0 ± 17.4 (Group S+) and 90.7 ± 9.9 (Group S-) (P = 0.39), and anterior tibial translation differences were 2.8 ± 3.0 mm (Group S+) and 2.7 ± 2.9 mm (Group S-) (P = 0.73). All these values represent postoperative measurements. No significant discrepancies existed between groups across evaluation methods.

CONCLUSIONS: This study's results suggest that Segond fractures have minimal impact on clinical ACL reconstruction outcomes, as assessed through both patient-reported subjective evaluations and objective healthcare provider evaluations. Segond fractures' significance in postoperative outcomes questions the necessity of ALS reconstruction.}, } @article {pmid38645254, year = {2024}, author = {Card, NS and Wairagkar, M and Iacobacci, C and Hou, X and Singer-Clark, T and Willett, FR and Kunz, EM and Fan, C and Nia, MV and Deo, DR and Srinivasan, A and Choi, EY and Glasser, MF and Hochberg, LR and Henderson, JM and Shahlaie, K and Brandman, DM and Stavisky, SD}, title = {An accurate and rapidly calibrating speech neuroprosthesis.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, pmid = {38645254}, support = {DP2 DC021055/DC/NIDCD NIH HHS/United States ; U01 DC017844/DC/NIDCD NIH HHS/United States ; U01 DC019430/DC/NIDCD NIH HHS/United States ; }, abstract = {Brain-computer interfaces can enable rapid, intuitive communication for people with paralysis by transforming the cortical activity associated with attempted speech into text on a computer screen. Despite recent advances, communication with brain-computer interfaces has been restricted by extensive training data requirements and inaccurate word output. A man in his 40's with ALS with tetraparesis and severe dysarthria (ALSFRS-R = 23) was enrolled into the BrainGate2 clinical trial. He underwent surgical implantation of four microelectrode arrays into his left precentral gyrus, which recorded neural activity from 256 intracortical electrodes. We report a speech neuroprosthesis that decoded his neural activity as he attempted to speak in both prompted and unstructured conversational settings. Decoded words were displayed on a screen, then vocalized using text-to-speech software designed to sound like his pre-ALS voice. On the first day of system use, following 30 minutes of attempted speech training data, the neuroprosthesis achieved 99.6% accuracy with a 50-word vocabulary. On the second day, the size of the possible output vocabulary increased to 125,000 words, and, after 1.4 additional hours of training data, the neuroprosthesis achieved 90.2% accuracy. With further training data, the neuroprosthesis sustained 97.5% accuracy beyond eight months after surgical implantation. The participant has used the neuroprosthesis to communicate in self-paced conversations for over 248 hours. In an individual with ALS and severe dysarthria, an intracortical speech neuroprosthesis reached a level of performance suitable to restore naturalistic communication after a brief training period.}, } @article {pmid38645132, year = {2024}, author = {Caggiano, C and Morselli, M and Qian, X and Celona, B and Thompson, M and Wani, S and Tosevska, A and Taraszka, K and Heuer, G and Ngo, S and Steyn, F and Nestor, P and Wallace, L and McCombe, P and Heggie, S and Thorpe, K and McElligott, C and English, G and Henders, A and Henderson, R and Lomen-Hoerth, C and Wray, N and McRae, A and Pellegrini, M and Garton, F and Zaitlen, N}, title = {Tissue informative cell-free DNA methylation sites in amyotrophic lateral sclerosis.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, pmid = {38645132}, support = {T32 NS048004/NS/NINDS NIH HHS/United States ; }, abstract = {Cell-free DNA (cfDNA) is increasingly recognized as a promising biomarker candidate for disease monitoring. However, its utility in neurodegenerative diseases, like amyotrophic lateral sclerosis (ALS), remains underexplored. Existing biomarker discovery approaches are tailored to a specific disease context or are too expensive to be clinically practical. Here, we address these challenges through a new approach combining advances in molecular and computational technologies. First, we develop statistical tools to select tissue-informative DNA methylation sites relevant to a disease process of interest. We then employ a capture protocol to select these sites and perform targeted methylation sequencing. Multi-modal information about the DNA methylation patterns are then utilized in machine learning algorithms trained to predict disease status and disease progression. We applied our method to two independent cohorts of ALS patients and controls (n=192). Overall, we found that the targeted sites accurately predicted ALS status and replicated between cohorts. Additionally, we identified epigenetic features associated with ALS phenotypes, including disease severity. These findings highlight the potential of cfDNA as a non-invasive biomarker for ALS.}, } @article {pmid38644973, year = {2024}, author = {Gonzalez, D and Cuenca, X and Allende, ML}, title = {Knockdown of tgfb1a partially improves ALS phenotype in a transient zebrafish model.}, journal = {Frontiers in cellular neuroscience}, volume = {18}, number = {}, pages = {1384085}, pmid = {38644973}, issn = {1662-5102}, abstract = {Amyotrophic lateral sclerosis (ALS) corresponds to a neurodegenerative disorder marked by the progressive degeneration of both upper and lower motor neurons located in the brain, brainstem, and spinal cord. ALS can be broadly categorized into two main types: sporadic ALS (sALS), which constitutes approximately 90% of all cases, and familial ALS (fALS), which represents the remaining 10% of cases. Transforming growth factor type-β (TGF-β) is a cytokine involved in various cellular processes and pathological contexts, including inflammation and fibrosis. Elevated levels of TGF-β have been observed in the plasma and cerebrospinal fluid (CSF) of both ALS patients and mouse models. In this perspective, we explore the impact of the TGF-β signaling pathway using a transient zebrafish model for ALS. Our findings reveal that the knockdown of tgfb1a lead to a partial prevention of motor axon abnormalities and locomotor deficits in a transient ALS zebrafish model at 48 h post-fertilization (hpf). In this context, we delve into the proposed distinct roles of TGF-β in the progression of ALS. Indeed, some evidence suggests a dual role for TGF-β in ALS progression. Initially, it seems to exert a neuroprotective effect in the early stages, but paradoxically, it may contribute to disease progression in later stages. Consequently, we suggest that the TGF-β signaling pathway emerges as an attractive therapeutic target for treating ALS. Nevertheless, further research is crucial to comprehensively understand the nuanced role of TGF-β in the pathological context.}, } @article {pmid38644578, year = {2024}, author = {Yao, Q and Long, C and Yi, P and Zhang, G and Wan, W and Rao, X and Ying, J and Liang, W and Hua, F}, title = {C/EBPβ: A transcription factor associated with the irreversible progression of Alzheimer's disease.}, journal = {CNS neuroscience & therapeutics}, volume = {30}, number = {4}, pages = {e14721}, pmid = {38644578}, issn = {1755-5949}, support = {jxsq2019201023//Jiangxi Province "Double Thousand Plan"/ ; 82060219//National Natural Science Foundation of China/ ; 82271234//National Natural Science Foundation of China/ ; 20212ACB216009//Natural Science Foundation of Jiangxi Province/ ; 20212BAB216048//Natural Science Foundation of Jiangxi Province/ ; 2019YNTD12003//Youth Team Project of the Second Affiliated Hospital of Nanchang University/ ; }, mesh = {Humans ; *Alzheimer Disease/metabolism/pathology ; *CCAAT-Enhancer-Binding Protein-beta/metabolism/genetics ; *Disease Progression ; Animals ; Amyloid beta-Peptides/metabolism ; }, abstract = {BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disorder distinguished by a swift cognitive deterioration accompanied by distinctive pathological hallmarks such as extracellular Aβ (β-amyloid) peptides, neuronal neurofibrillary tangles (NFTs), sustained neuroinflammation, and synaptic degeneration. The elevated frequency of AD cases and its proclivity to manifest at a younger age present a pressing challenge in the quest for novel therapeutic interventions. Numerous investigations have substantiated the involvement of C/EBPβ in the progression of AD pathology, thus indicating its potential as a therapeutic target for AD treatment.

AIMS: Several studies have demonstrated an elevation in the expression level of C/EBPβ among individuals afflicted with AD. Consequently, this review predominantly delves into the association between C/EBPβ expression and the pathological progression of Alzheimer's disease, elucidating its underlying molecular mechanism, and pointing out the possibility that C/EBPβ can be a new therapeutic target for AD.

METHODS: A systematic literature search was performed across multiple databases, including PubMed, Google Scholar, and so on, utilizing predetermined keywords and MeSH terms, without temporal constraints. The inclusion criteria encompassed diverse study designs, such as experimental, case-control, and cohort studies, restricted to publications in the English language, while conference abstracts and unpublished sources were excluded.

RESULTS: Overexpression of C/EBPβ exacerbates the pathological features of AD, primarily by promoting neuroinflammation and mediating the transcriptional regulation of key molecular pathways, including δ-secretase, apolipoprotein E4 (APOE4), acidic leucine-rich nuclear phosphoprotein-32A (ANP32A), transient receptor potential channel 1 (TRPC1), and Forkhead BoxO (FOXO).

DISCUSSION: The correlation between overexpression of C/EBPβ and the pathological development of AD, along with its molecular mechanisms, is evident. Investigating the pathways through which C/EBPβ regulates the development of AD reveals numerous multiple vicious cycle pathways exacerbating the pathological progression of the disease. Furthermore, the exacerbation of pathological progression due to C/EBPβ overexpression and its molecular mechanism is not limited to AD but also extends to other neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), and multiple sclerosis (MS).

CONCLUSION: The overexpression of C/EBPβ accelerates the irreversible progression of AD pathophysiology. Additionally, C/EBPβ plays a crucial role in mediating multiple pathways linked to AD pathology, some of which engender vicious cycles, leading to the establishment of feedback mechanisms. To sum up, targeting C/EBPβ could hold promise as a therapeutic strategy not only for AD but also for other degenerative diseases.}, } @article {pmid38644373, year = {2024}, author = {Niccolai, E and Pedone, M and Martinelli, I and Nannini, G and Baldi, S and Simonini, C and Di Gloria, L and Zucchi, E and Ramazzotti, M and Spezia, PG and Maggi, F and Quaranta, G and Masucci, L and Bartolucci, G and Stingo, FC and Mandrioli, J and Amedei, A}, title = {Amyotrophic lateral sclerosis stratification: unveiling patterns with virome, inflammation, and metabolism molecules.}, journal = {Journal of neurology}, volume = {271}, number = {7}, pages = {4310-4325}, pmid = {38644373}, issn = {1432-1459}, support = {Grant-No. RF-2016-02361616//Ministero della Salute/ ; Grant no. B008-P00634//University of Florence/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/blood/immunology ; Male ; Female ; Middle Aged ; Aged ; *Inflammation/blood ; *Virome ; Cytokines/blood ; Torque teno virus/genetics ; Fatty Acids, Nonesterified/blood ; Adult ; Biomarkers/blood ; DNA, Viral/blood ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is an untreatable and clinically heterogeneous condition primarily affecting motor neurons. The ongoing quest for reliable biomarkers that mirror the disease status and progression has led to investigations that extend beyond motor neurons' pathology, encompassing broader systemic factors such as metabolism, immunity, and the microbiome. Our study contributes to this effort by examining the potential role of microbiome-related components, including viral elements, such as torque tenovirus (TTV), and various inflammatory factors, in ALS. In our analysis of serum samples from 100 ALS patients and 34 healthy controls (HC), we evaluated 14 cytokines, TTV DNA load, and 18 free fatty acids (FFA). We found that the evaluated variables are effective in differentiating ALS patients from healthy controls. In addition, our research identifies four unique patient clusters, each characterized by distinct biological profiles. Intriguingly, no correlations were found with site of onset, sex, progression rate, phenotype, or C9ORF72 expansion. A remarkable aspect of our findings is the discovery of a gender-specific relationship between levels of 2-ethylhexanoic acid and patient survival. In addition to contributing to the growing body of evidence suggesting altered peripheral immune responses in ALS, our exploratory research underscores metabolic diversity challenging conventional clinical classifications. If our exploratory findings are validated by further research, they could significantly impact disease understanding and patient care customization. Identifying groups based on biological profiles might aid in clustering patients with varying responses to treatments.}, } @article {pmid38643758, year = {2024}, author = {Aiello, EN and Solca, F and Torre, S and Colombo, E and Maranzano, A and De Lorenzo, A and Patisso, V and Treddenti, M and Curti, B and Morelli, C and Doretti, A and Verde, F and Ferrucci, R and Barbieri, S and Ruggiero, F and Priori, A and Silani, V and Ticozzi, N and Poletti, B}, title = {Longitudinal Feasibility of the Montreal Cognitive Assessment (MoCA) in Non-Demented ALS Patients.}, journal = {European neurology}, volume = {87}, number = {2}, pages = {79-83}, doi = {10.1159/000538828}, pmid = {38643758}, issn = {1421-9913}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/complications ; Male ; Female ; *Feasibility Studies ; *Mental Status and Dementia Tests/standards ; Middle Aged ; Aged ; Longitudinal Studies ; Reproducibility of Results ; Cognitive Dysfunction/etiology/diagnosis ; Disease Progression ; Italy ; Neuropsychological Tests/standards ; }, abstract = {INTRODUCTION: The present study aimed at testing the longitudinal feasibility of the Montreal Cognitive Assessment (MoCA) in an Italian cohort of non-demented amyotrophic lateral sclerosis (ALS) patients.

METHODS: N = 39 non-demented ALS patients were followed-up at a 5-to-10-month interval (M = 6.8; SD = 1.4) with the MoCA and the Edinburgh Cognitive and Behavioral ALS Screen (ECAS). Practice effects, test-retest reliability, and predictive validity (against follow-up ECAS scores) were assessed. Reliable change indices (RCIs) were derived via a regression-based approach by accounting for retest interval and baseline confounders (i.e., demographics, disease duration, and severity and progression rate).

RESULTS: At retest, 100% and 69.2% of patients completed the ECAS and the MoCA, respectively. Patients who could not complete the MoCA showed a slightly more severe and fast-progressing disease. The MoCA was not subject to practice effects (t[32] = -0.80; p = 0.429) and was reliable at retest (intra-class correlation = 0.82). Moreover, baseline MoCA scores predicted the ECAS at retest. RCIs were successfully derived - with baseline MoCA scores being the only significant predictor of retest performances (ps < 0.001).

CONCLUSIONS: As long as motor disabilities do not undermine its applicability, the MoCA appears to be longitudinally feasible at a 5-to-10-month interval in non-demented ALS patients. However, ALS-specific screeners - such as the ECAS - should be preferred whenever possible.}, } @article {pmid38643177, year = {2024}, author = {Jeszka, J and Hummel, D and Woźniewicz, M and Morinaka, T and Sone, Y and Crews, DE}, title = {Allostatic load and frailty do not covary significantly among older residents of Greater Poland.}, journal = {Journal of physiological anthropology}, volume = {43}, number = {1}, pages = {12}, pmid = {38643177}, issn = {1880-6805}, mesh = {Male ; Humans ; Female ; Aged ; *Allostasis/physiology ; *Frailty/epidemiology ; Poland/epidemiology ; Biomarkers ; Cohort Studies ; }, abstract = {BACKGROUND: Physiological dysregulation/allostatic load and the geriatric syndrome frailty increase with age. As a neurophysiological response system, allostasis supports survival by limiting stressor-related damage. Frailty reflects decreased strength, endurance, and physical abilities secondary to losses of muscle and bone with age. One suggestion, based on large cohort studies of person's ages 70 + years, is that frailty contributes to allostatic load at older ages. However, small community-based research has not confirmed this specific association.

METHODS: To further explore possible associations between allostatic load and frailty, we enrolled 211 residents of Greater Poland aged 55-91 years living in a small village (Nekla, N = 104) and an urban center and capital of Greater Poland (Poznan, N = 107). For each, we recorded age, self-reported sex, and residence and estimated a 10-biomarker allostatic load score (ALS) and an 8-biomarker frailty index. We anticipated the following: higher ALS and frailty among men and rural residents; for frailty but not ALS to be higher at older ages; significant associations of ALS with sex and place of residence, but not with age or frailty. The significance of observed associations was evaluated by t-tests and multivariate regression.

RESULTS: ALS did not vary significantly between men and women nor between Nekla and Poznan residents overall. However, women showed significantly higher frailty than men. Nekla men showed significantly higher ALS but not frailty, while Nekla women showed nonsignificantly higher ALS and lower frailty than Poznan. In multivariate analyses, neither age, nor sex, nor residence was associated with ALS. Conversely, age, sex, and residence, but not ALS, are associated significantly with frailty. In Nekla, both age and sex, but in Poznan only age, are associated with ALS. Among women, both age and residence, but among men, neither associated with ALS. In no case did ALS associate significantly with frailty.

CONCLUSION: In this sample, lifestyle factors associated with residence, age, and sex influence stress-related physiology, less so in women, while ALS and frailty do not covary, suggesting their underlying promoters are distinct. Similar complex associations of physiological dysregulation with frailty, age, sex, and residence likely exist within many local settings. Knowledge of this variation likely will aid in supporting health and healthcare services among seniors.}, } @article {pmid38643019, year = {2024}, author = {Guo, J and You, L and Zhou, Y and Hu, J and Li, J and Yang, W and Tang, X and Sun, Y and Gu, Y and Dong, Y and Chen, X and Sato, C and Zinman, L and Rogaeva, E and Wang, J and Chen, Y and Zhang, M}, title = {Spatial enrichment and genomic analyses reveal the link of NOMO1 with amyotrophic lateral sclerosis.}, journal = {Brain : a journal of neurology}, volume = {147}, number = {8}, pages = {2826-2841}, doi = {10.1093/brain/awae123}, pmid = {38643019}, issn = {1460-2156}, support = {82071430//National Natural Science Foundation of China/ ; 22ZR1466400//Shanghai Municipal Natural Science Foundation General Program/ ; //Fundamental Research Funds/ ; //Central Universities/ ; #2021ZD0201100//Science Innovation 2030 - Brain Science and Brain-Inspired Intelligence Technology Major Project/ ; //Ministry of Science and Technology/ ; //ALS Society of Canada and Canadian Consortium on Neurodegeneration in Aging/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/genetics/pathology ; Humans ; Mice ; Animals ; *Motor Cortex/metabolism/pathology ; Transcriptome ; Genomics/methods ; Prefrontal Cortex/metabolism/pathology ; Motor Neurons/metabolism/pathology ; Male ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a severe motor neuron disease with uncertain genetic predisposition in most sporadic cases. The spatial architecture of cell types and gene expression are the basis of cell-cell interactions, biological function and disease pathology, but are not well investigated in the human motor cortex, a key ALS-relevant brain region. Recent studies indicated single nucleus transcriptomic features of motor neuron vulnerability in ALS motor cortex. However, the brain regional vulnerability of ALS-associated genes and the genetic link between region-specific genes and ALS risk remain largely unclear. Here, we developed an entropy-weighted differential gene expression matrix-based tool (SpatialE) to identify the spatial enrichment of gene sets in spatial transcriptomics. We benchmarked SpatialE against another enrichment tool (multimodal intersection analysis) using spatial transcriptomics data from both human and mouse brain tissues. To investigate regional vulnerability, we analysed three human motor cortex and two dorsolateral prefrontal cortex tissues for spatial enrichment of ALS-associated genes. We also used Cell2location to estimate the abundance of cell types in ALS-related cortex layers. To dissect the link of regionally expressed genes and ALS risk, we performed burden analyses of rare loss-of-function variants detected by whole-genome sequencing in ALS patients and controls, then analysed differential gene expression in the TargetALS RNA-sequencing dataset. SpatialE showed more accurate and specific spatial enrichment of regional cell type markers than multimodal intersection analysis in both mouse brain and human dorsolateral prefrontal cortex. Spatial transcriptomic analyses of human motor cortex showed heterogeneous cell types and spatial gene expression profiles. We found that 260 manually curated ALS-associated genes are significantly enriched in layer 5 of the motor cortex, with abundant expression of upper motor neurons and layer 5 excitatory neurons. Burden analyses of rare loss-of-function variants in Layer 5-associated genes nominated NOMO1 as a novel ALS-associated gene in a combined sample set of 6814 ALS patients and 3324 controls (P = 0.029). Gene expression analyses in CNS tissues revealed downregulation of NOMO1 in ALS, which is consistent with a loss-of-function disease mechanism. In conclusion, our integrated spatial transcriptomics and genomic analyses identified regional brain vulnerability in ALS and the association of a layer 5 gene (NOMO1) with ALS risk.}, } @article {pmid38643008, year = {2024}, author = {Zheng, Q and Zeng, Z and Tang, X and Ma, L}, title = {Impact of an ICU bed capacity optimisation method on the average length of stay and average cost of hospitalisation following implementation of China's open policy with respect to COVID-19: a difference-in-differences analysis based on information management system data from a tertiary hospital in southwest China.}, journal = {BMJ open}, volume = {14}, number = {4}, pages = {e078069}, pmid = {38643008}, issn = {2044-6055}, mesh = {Humans ; *COVID-19/epidemiology ; Length of Stay ; Tertiary Care Centers ; Hospitalization ; Intensive Care Units ; China/epidemiology ; Information Management ; }, abstract = {OBJECTIVES: Following the implementation of China's open policy with respect to COVID-19 on 7 December 2022, the influx of patients with infectious diseases has surged rapidly, necessitating hospitals to adopt temporary requisition and modification of ward beds to optimise hospital bed capacity and alleviate the burden of overcrowded patients. This study aims to investigate the effect of an intensive care unit (ICU) bed capacity optimisation method on the average length of stay (ALS) and average cost of hospitalisation (ACH) after the open policy of COVID-19 in China.

DESIGN AND SETTING: A difference-in-differences (DID) approach is employed to analyse and compare the ALS and ACH of patients in four modified ICUs and eight non-modified ICUs within a tertiary hospital located in southwest China. The analysis spans 2 months before and after the open policy, specifically from 5 October 2022 to 6 December 2022, and 7 December 2022 to 6 February 2023.

PARTICIPANTS: We used the daily data extracted from the hospital's information management system for a total of 5944 patients admitted by the outpatient and emergency access during the 2-month periods before and after the release of the open policy in China.

RESULTS: The findings indicate that the ICU bed optimisation method implemented by the tertiary hospital led to a significant reduction in ALS (HR -0.6764, 95% CI -1.0328 to -0.3201, p=0.000) and ACH (HR -0.2336, 95% CI -0.4741 to -0.0068, p=0.057) among ICU patients after implementation of the open policy. These results were robust across various sensitivity analyses. However, the effect of the optimisation method exhibits heterogeneity among patients admitted through the outpatient and emergency channels.

CONCLUSIONS: This study corroborates a significant positive impact of ICU bed optimisation in mitigating the shortage of medical resources following an epidemic outbreak. The findings hold theoretical and practical implications for identifying effective emergency coordination strategies in managing hospital bed resources during sudden public health emergency events. These insights contribute to the advancement of resource management practices and the promotion of experiences in dealing with public health emergencies.}, } @article {pmid38642323, year = {2024}, author = {Ferrari, V and Conti, M and Bovenzi, R and Cerroni, R and Pierantozzi, M and Mercuri, NB and Stefani, A}, title = {Rare association between spinocerebellar ataxia and amyotrophic lateral sclerosis: a case series.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {45}, number = {9}, pages = {4367-4371}, pmid = {38642323}, issn = {1590-3478}, mesh = {Humans ; Male ; Middle Aged ; *Amyotrophic Lateral Sclerosis/genetics/diagnosis/complications ; *Spinocerebellar Ataxias/genetics/complications/physiopathology ; *Ataxin-2/genetics ; Trinucleotide Repeat Expansion/genetics ; }, abstract = {INTRODUCTION: In this work, we describe a new case of association between SCA2 and MND.

CASE REPORT: A 58-year-old man who was diagnosed with spinocerebellar ataxia type 2 presented dysphagia and a significant decline in his ability to walk, with a reduction in autonomy and the need to use a wheelchair. We performed electromyography and electroneurography of the four limbs and of the cranial district and motor-evoked potentials to study upper and lower motor neurons. Referring to the revised El Escorial criteria of 2015, ALS diagnosis was made.

DISCUSSION: Considering different cases described in literature over the years, SCA2 could represent an important risk factor for developing ALS. In particular, the presence of alleles of ATXN2 with 27 and 28 CAG repeats seems to slightly decrease the risk of developing the disease, which would instead be progressively increased by the presence of alleles with 29, 30, 31, 32, and 33 repeats. The exact physiopathological mechanism by which the mutation increases the risk of developing the disease is currently unknown. Transcriptomic studies on mouse models have demonstrated the involvement of several pathways, including the innate immunity regulation by STING and the biosynthesis of fatty acid and cholesterol by SREBP.

CONCLUSION: CAG repeat expansions in the ATXN2 gene have been associated with variable neurological presentations, which include SCA2, ALS, Parkinsonism, or a combination of them. Further research is needed to understand the relationship between SCA2 and ALS better and explore molecular underlying mechanisms.}, } @article {pmid38641715, year = {2024}, author = {Udine, E and DeJesus-Hernandez, M and Tian, S and das Neves, SP and Crook, R and Finch, NA and Baker, MC and Pottier, C and Graff-Radford, NR and Boeve, BF and Petersen, RC and Knopman, DS and Josephs, KA and Oskarsson, B and Da Mesquita, S and Petrucelli, L and Gendron, TF and Dickson, DW and Rademakers, R and van Blitterswijk, M}, title = {Abundant transcriptomic alterations in the human cerebellum of patients with a C9orf72 repeat expansion.}, journal = {Acta neuropathologica}, volume = {147}, number = {1}, pages = {73}, pmid = {38641715}, issn = {1432-0533}, support = {R35 NS097273/NS/NINDS NIH HHS/United States ; R01 NS120992/NS/NINDS NIH HHS/United States ; R35 NS097261/NS/NINDS NIH HHS/United States ; R21 NS110994/NS/NINDS NIH HHS/United States ; UH3 NS103870/NS/NINDS NIH HHS/United States ; P01 NS084974/NS/NINDS NIH HHS/United States ; R01 AG037491/AG/NIA NIH HHS/United States ; UG3 NS103870/NS/NINDS NIH HHS/United States ; R01 NS121125/NS/NINDS NIH HHS/United States ; RF1 NS123052/NS/NINDS NIH HHS/United States ; RF1 NS120992/NS/NINDS NIH HHS/United States ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology ; *C9orf72 Protein/genetics/metabolism ; *Cerebellum/pathology ; DNA Repeat Expansion/genetics ; *Frontotemporal Lobar Degeneration/genetics/metabolism/pathology ; Gene Expression Profiling ; Transcriptome ; }, abstract = {The most prominent genetic cause of both amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) is a repeat expansion in the gene C9orf72. Importantly, the transcriptomic consequences of the C9orf72 repeat expansion remain largely unclear. Here, we used short-read RNA sequencing (RNAseq) to profile the cerebellar transcriptome, detecting alterations in patients with a C9orf72 repeat expansion. We focused on the cerebellum, since key C9orf72-related pathologies are abundant in this neuroanatomical region, yet TDP-43 pathology and neuronal loss are minimal. Consistent with previous work, we showed a reduction in the expression of the C9orf72 gene and an elevation in homeobox genes, when comparing patients with the expansion to both patients without the C9orf72 repeat expansion and control subjects. Interestingly, we identified more than 1000 alternative splicing events, including 4 in genes previously associated with ALS and/or FTLD. We also found an increase of cryptic splicing in C9orf72 patients compared to patients without the expansion and controls. Furthermore, we demonstrated that the expression level of select RNA-binding proteins is associated with cryptic splice junction inclusion. Overall, this study explores the presence of widespread transcriptomic changes in the cerebellum, a region not confounded by severe neurodegeneration, in post-mortem tissue from C9orf72 patients.}, } @article {pmid38640582, year = {2024}, author = {Ceccanti, M and Libonati, L and Moret, F and D'Andrea, E and Gori, MC and Bersani, FS and Inghilleri, M and Cambieri, C}, title = {Emotion recognition in amyotrophic lateral sclerosis in a dynamic environment.}, journal = {Journal of the neurological sciences}, volume = {460}, number = {}, pages = {123019}, doi = {10.1016/j.jns.2024.123019}, pmid = {38640582}, issn = {1878-5883}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/psychology/physiopathology/complications ; Male ; Female ; Middle Aged ; *Emotions/physiology ; Aged ; *Facial Expression ; Neuropsychological Tests ; Recognition, Psychology/physiology ; Facial Recognition/physiology ; Adult ; }, abstract = {OBJECTIVE: The aim of our study was to measure the ability of ALS patients to process dynamic facial expressions as compared to a control group of healthy subjects and to correlate this ability in ALS patients with neuropsychological, clinical and neurological measures of the disease.

METHODS: Sixty-three ALS patients and 47 healthy controls were recruited. All the ALS patients also underwent i) the Geneva Emotion Recognition Test (GERT) in which ten actors express 14 types of dynamic emotions in brief video clips with audio, ii) the Edimburgh Cognitive and Behavioral ALS Screen (ECAS) test; iii) the ALS Functional Rating Scale Revised (ALSFRS-R) and iv) the Medical Research Council (MRC) for the evaluation of muscle strength. All the healthy subjects enrolled in the study underwent the GERT.

RESULTS: The recognition of irritation and pleasure was significantly different between ALS patients and the control group. The amusement, despair, irritation, joy, sadness and surprise had been falsely recognized differently between the two groups. Specific ALS cognitive impairment was associated with bulbar-onset phenotype (OR = 14,3889; 95%CI = 3,96-52,16). No association was observed between false emotion recognition and cognitive impairment (F(1,60)=,56,971, p=,45,333). The number of categorical errors was significantly higher in the ALS patients than in the control group (27,66 ± 7,28 vs 17,72 ± 5,29; t = 8723; p = 0.001).

CONCLUSIONS: ALS patients show deficits in the dynamic processing of a wide range of emotions. These deficits are not necessarily associated with a decline in higher cognitive functions: this could therefore lead to an underestimation of the phenomenon.}, } @article {pmid38638511, year = {2024}, author = {Finsel, J and Rosenbohm, A and Peter, RS and Bäzner, H and Börtlein, A and Dempewolf, S and Schabet, M and Hecht, M and Kohler, A and Opherk, C and Nägele, A and Sommer, N and Lindner, A and Rothenbacher, D and Ludolph, AC and Nagel, G and Lulé, DE}, title = {Coping as a resource to allow for psychosocial adjustment in fatal disease: results from patients with amyotrophic lateral sclerosis.}, journal = {Frontiers in psychology}, volume = {15}, number = {}, pages = {1361767}, pmid = {38638511}, issn = {1664-1078}, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a fatal disorder, which imposes a severe emotional burden on patients. Appropriate coping mechanisms may alleviate this burden and facilitate wellbeing, with social support known to be a successful coping strategy. This observational study aimed to determine the interplay of general coping traits of hope for success and fear of failure, coping behavior of social activity, and patients' wellbeing.

METHODS: In this cross-sectional study, patients with ALS from a clinical-epidemiological registry in Southwestern Germany were interviewed regarding coping traits (achievement-motivated behavior: hope for success and fear of failure), coping behavior of social activity, and psychosocial adjustment, determined using measures of depressiveness, anxiety [both measured by Hospital Anxiety and Depression Scale (HADS)], and quality of life [Anamnestic Comparative Self-Assessment (ACSA)]. Demographics, clinical [ALS Functional Rating Scale revised version (ALSFRS-R)], and survival data were recorded.

RESULTS: A total of 868 patients [60.70% male patients, mean age: 64.70 (±10.83) years, mean ALSFRS-R: 37.36 ± 7.07] were interviewed. Anxiety in patients was found to be associated with a high fear of failure. In contrast, a generally positive attitude in patients exemplified in high hopes for success was associated with better wellbeing. Finally, coping behavior of social activity explained up to 65% of the variance of depressiveness among the patients with ALS.

CONCLUSION: In this study, we present evidence that the wellbeing of patients with ALS is not an immediate fatalistic consequence of physical degradation but rather determined by coping traits and behavior, which may be trained to substantially increase the wellbeing of patients with ALS.}, } @article {pmid38638178, year = {2023}, author = {Fotouhi, M and Worrall, D and Ayoubi, R and Southern, K and McPherson, PS and Laflamme, C and , and , }, title = {A guide to selecting high-performing antibodies for RNA-binding protein TIA1 for use in Western Blot, immunoprecipitation and immunofluorescence.}, journal = {F1000Research}, volume = {12}, number = {}, pages = {745}, pmid = {38638178}, issn = {2046-1402}, mesh = {T-Cell Intracellular Antigen-1/genetics ; *RNA-Binding Proteins ; Blotting, Western ; Fluorescent Antibody Technique ; Immunoprecipitation ; }, abstract = {A member of the RNA-binding protein family, T-cell intracellular antigen-1 (TIA1) regulates mRNA translation and splicing as well as cellular stress by promoting stress granule formation. Variants of the TIA1 gene have implications in neurogenerative disorders including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Reproducible research on TIA1 would be enhanced with the availability of high-quality anti-TIA1 antibodies. In this study, we characterized twelve TIA1 commercial antibodies for Western Blot, immunoprecipitation, and immunofluorescence using a standardized experimental protocol based on comparing read-outs in knockout cell lines and isogenic parental controls. We identified many high-performing antibodies and encourage readers to use this report as a guide to select the most appropriate antibody for their specific needs.}, } @article {pmid38636451, year = {2024}, author = {Khalil, B and Da Cruz, S}, title = {14-3-3θ, a novel player in TDP-43 pathophysiology: Implications for ALS/FTD.}, journal = {Neuron}, volume = {112}, number = {8}, pages = {1197-1199}, doi = {10.1016/j.neuron.2024.03.025}, pmid = {38636451}, issn = {1097-4199}, mesh = {Animals ; Mice ; *Amyotrophic Lateral Sclerosis/pathology ; DNA-Binding Proteins/genetics ; *Frontotemporal Dementia/genetics ; Mice, Transgenic ; Neurons/pathology ; *TDP-43 Proteinopathies/genetics ; Disease Models, Animal ; }, abstract = {In this issue of Neuron, Ke et al.[1] report a novel non-canonical interaction between 14-3-3θ and TDP-43 that impacts loss-of-function and gain-of-toxic pathology in TDP-43 proteinopathies. The authors further provide proof of principle for a 14-3-3θ-targeted gene therapy to reduce TDP-43-induced deficits in transgenic TDP-43 mutant mice.}, } @article {pmid38636436, year = {2024}, author = {Suazo, KF and Mishra, V and Maity, S and Auger, SA and Justyna, K and Petre, AM and Ottoboni, L and Ongaro, J and Corti, SP and Lotti, F and Przedborski, S and Distefano, MD}, title = {Improved synthesis and application of an alkyne-functionalized isoprenoid analogue to study the prenylomes of motor neurons, astrocytes and their stem cell progenitors.}, journal = {Bioorganic chemistry}, volume = {147}, number = {}, pages = {107365}, pmid = {38636436}, issn = {1090-2120}, support = {R01 NS107442/NS/NINDS NIH HHS/United States ; P30 CA077598/CA/NCI NIH HHS/United States ; R21 NS101575/NS/NINDS NIH HHS/United States ; T32 AG029796/AG/NIA NIH HHS/United States ; T32 GM132029/GM/NIGMS NIH HHS/United States ; R35 GM141853/GM/NIGMS NIH HHS/United States ; }, mesh = {*Astrocytes/metabolism/cytology ; Animals ; *Protein Prenylation ; *Alkynes/chemistry/chemical synthesis ; *Motor Neurons/metabolism/cytology ; Terpenes/chemistry/chemical synthesis/metabolism ; Mice ; Molecular Structure ; Cells, Cultured ; }, abstract = {Protein prenylation is one example of a broad class of post-translational modifications where proteins are covalently linked to various hydrophobic moieties. To globally identify and monitor levels of all prenylated proteins in a cell simultaneously, our laboratory and others have developed chemical proteomic approaches that rely on the metabolic incorporation of isoprenoid analogues bearing bio-orthogonal functionality followed by enrichment and subsequent quantitative proteomic analysis. Here, several improvements in the synthesis of the alkyne-containing isoprenoid analogue C15AlkOPP are reported to improve synthetic efficiency. Next, metabolic labeling with C15AlkOPP was optimized to obtain useful levels of metabolic incorporation of the probe in several types of primary cells. Those conditions were then used to study the prenylomes of motor neurons (ES-MNs), astrocytes (ES-As), and their embryonic stem cell progenitors (ESCs), which allowed for the identification of 54 prenylated proteins from ESCs, 50 from ES-MNs, and 84 from ES-As, representing all types of prenylation. Bioinformatic analysis revealed specific enriched pathways, including nervous system development, chemokine signaling, Rho GTPase signaling, and adhesion. Hierarchical clustering showed that most enriched pathways in all three cell types are related to GTPase activity and vesicular transport. In contrast, STRING analysis showed significant interactions in two populations that appear to be cell type dependent. The data provided herein demonstrates that robust incorporation of C15AlkOPP can be obtained in ES-MNs and related primary cells purified via magnetic-activated cell sorting allowing the identification and quantification of numerous prenylated proteins. These results suggest that metabolic labeling with C15AlkOPP should be an effective approach for investigating the role of prenylated proteins in primary cells in both normal cells and disease pathologies, including ALS.}, } @article {pmid38635657, year = {2024}, author = {Castellanos Otero, P and Todd, TW and Shao, W and Jones, CJ and Huang, K and Daughrity, LM and Yue, M and Sheth, U and Gendron, TF and Prudencio, M and Oskarsson, B and Dickson, DW and Petrucelli, L and Zhang, YJ}, title = {Generation and characterization of monoclonal antibodies against pathologically phosphorylated TDP-43.}, journal = {PloS one}, volume = {19}, number = {4}, pages = {e0298080}, pmid = {38635657}, issn = {1932-6203}, support = {R35 NS097273/NS/NINDS NIH HHS/United States ; RF1 AG062171/AG/NIA NIH HHS/United States ; RF1 AG062077/AG/NIA NIH HHS/United States ; P01 AG019724/AG/NIA NIH HHS/United States ; R21 NS127331/NS/NINDS NIH HHS/United States ; P01 NS084974/NS/NINDS NIH HHS/United States ; R01 NS117461/NS/NINDS NIH HHS/United States ; P01 NS099114/NS/NINDS NIH HHS/United States ; U54 NS123743/NS/NINDS NIH HHS/United States ; }, mesh = {Mice ; Animals ; Humans ; *Amyotrophic Lateral Sclerosis/genetics ; *Frontotemporal Dementia/pathology ; Antibodies, Monoclonal ; HEK293 Cells ; DNA-Binding Proteins/genetics ; *TDP-43 Proteinopathies ; }, abstract = {Inclusions containing TAR DNA binding protein 43 (TDP-43) are a pathological hallmark of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). One of the disease-specific features of TDP-43 inclusions is the aberrant phosphorylation of TDP-43 at serines 409/410 (pS409/410). Here, we developed rabbit monoclonal antibodies (mAbs) that specifically detect pS409/410-TDP-43 in multiple model systems and FTD/ALS patient samples. Specifically, we identified three mAbs (26H10, 2E9 and 23A1) from spleen B cell clones that exhibit high specificity and sensitivity to pS409/410-TDP-43 peptides in an ELISA assay. Biochemical analyses revealed that pS409/410 of recombinant TDP-43 and of exogenous 25 kDa TDP-43 C-terminal fragments in cultured HEK293T cells are detected by all three mAbs. Moreover, the mAbs detect pS409/410-positive TDP-43 inclusions in the brains of FTD/ALS patients and mouse models of TDP-43 proteinopathy by immunohistochemistry. Our findings indicate that these mAbs are a valuable resource for investigating TDP-43 pathology both in vitro and in vivo.}, } @article {pmid38633814, year = {2024}, author = {Zhang, S and Moll, T and Rubin-Sigler, J and Tu, S and Li, S and Yuan, E and Liu, M and Butt, A and Harvey, C and Gornall, S and Alhalthli, E and Shaw, A and Souza, CDS and Ferraiuolo, L and Hornstein, E and Shelkovnikova, T and van Dijk, CH and Timpanaro, IS and Kenna, KP and Zeng, J and Tsao, PS and Shaw, PJ and Ichida, JK and Cooper-Knock, J and Snyder, MP}, title = {Deep learning modeling of rare noncoding genetic variants in human motor neurons defines CCDC146 as a therapeutic target for ALS.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, pmid = {38633814}, support = {/WT_/Wellcome Trust/United Kingdom ; P50 HG007735/HG/NHGRI NIH HHS/United States ; R01 NS097850/NS/NINDS NIH HHS/United States ; R01 NS131409/NS/NINDS NIH HHS/United States ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal and incurable neurodegenerative disease caused by the selective and progressive death of motor neurons (MNs). Understanding the genetic and molecular factors influencing ALS survival is crucial for disease management and therapeutics. In this study, we introduce a deep learning-powered genetic analysis framework to link rare noncoding genetic variants to ALS survival. Using data from human induced pluripotent stem cell (iPSC)-derived MNs, this method prioritizes functional noncoding variants using deep learning, links cis-regulatory elements (CREs) to target genes using epigenomics data, and integrates these data through gene-level burden tests to identify survival-modifying variants, CREs, and genes. We apply this approach to analyze 6,715 ALS genomes, and pinpoint four novel rare noncoding variants associated with survival, including chr7:76,009,472:C>T linked to CCDC146. CRISPR-Cas9 editing of this variant increases CCDC146 expression in iPSC-derived MNs and exacerbates ALS-specific phenotypes, including TDP-43 mislocalization. Suppressing CCDC146 with an antisense oligonucleotide (ASO), showing no toxicity, completely rescues ALS-associated survival defects in neurons derived from sporadic ALS patients and from carriers of the ALS-associated G4C2-repeat expansion within C9ORF72. ASO targeting of CCDC146 may be a broadly effective therapeutic approach for ALS. Our framework provides a generic and powerful approach for studying noncoding genetics of complex human diseases.}, } @article {pmid38632611, year = {2024}, author = {Dai, T and Lou, J and Kong, D and Li, J and Ren, Q and Chen, Y and Sun, S and Yun, Y and Sun, X and Yang, Y and Shao, K and Li, W and Zhao, Y and Meng, X and Yan, C and Lin, P and Liu, S}, title = {Choroid plexus enlargement in amyotrophic lateral sclerosis patients and its correlation with clinical disability and blood-CSF barrier permeability.}, journal = {Fluids and barriers of the CNS}, volume = {21}, number = {1}, pages = {36}, pmid = {38632611}, issn = {2045-8118}, support = {22-8-7-smjk-1-nsh//Qingdao Science and Technology Benefit People Demonstration Guide Special Project/ ; 2020M672067//China Postdoctoral Science Foundation/ ; NSFC82001354//National Natural Science Foundation of China/ ; }, mesh = {Animals ; Humans ; Choroid Plexus ; *Amyotrophic Lateral Sclerosis ; Retrospective Studies ; *Neurodegenerative Diseases ; Capillary Permeability ; }, abstract = {BACKGROUND: Using in vivo neuroimaging techniques, growing evidence has demonstrated that the choroid plexus (CP) volume is enlarged in patients with several neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease. However, although animal and postmortem findings suggest that CP abnormalities are likely important pathological mechanisms underlying amyotrophic lateral sclerosis (ALS), the third most common neurodegenerative disease, no available study has been conducted to thoroughly assess CP abnormalities and their clinical relevance in vivo in ALS patients to date. Thus, we aimed to determine whether in vivo CP enlargement may occur in ALS patients. We also aimed to identify the relationships of CP volume with clinical disabilities and blood-CSF barrier (BCSFB) permeability in ALS patients.

METHODS: In this retrospective study, based on structural MRI data, CP volume was assessed using a Gaussian mixture model and underwent further manual correction in 155 ALS patients and 105 age- and sex-matched HCs from October 2021 to April 2023. The ALS Functional Rating Scale-Revised (ALSFRS-R) was used to assess clinical disability. The CSF/serum albumin quotient (Qalb) was used to assess BCSFB permeability. Moreover, all the ALS patients completed genetic testing, and according to genetic testing, the ALS patients were further divided into genetic ALS subgroup and sporadic ALS subgroup.

RESULTS: We found that compared with HCs, ALS patients had a significantly higher CP volume (p < 0.001). Moreover, compared with HCs, CP volume was significantly increased in both ALS patients with and without known genetic mutations after family-wise error correction (p = 0.006 and p < 0.001, respectively), while there were no significant differences between the two ALS groups. Furthermore, the CP volume was significantly correlated with the ALSFRS-r score (r = -0.226; p = 0.005) and the Qalb (r = 0.479; p < 0.001) in ALS patients.

CONCLUSION: Our study first demonstrates CP enlargement in vivo in ALS patients, and continues to suggest an important pathogenetic role for CP abnormalities in ALS. Moreover, assessing CP volume is likely a noninvasive and easy-to-implement approach for screening BCSFB dysfunction in ALS patients.}, } @article {pmid38632300, year = {2024}, author = {Shiramasa, Y and Yamamoto, R and Kashiwagi, N and Sasaki, F and Imai, S and Ike, M and Kitazawa, S and Kameda, T and Kitahara, R}, title = {An aberrant fused in sarcoma liquid droplet of amyotrophic lateral sclerosis pathological variant, R495X, accelerates liquid-solid phase transition.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {8914}, pmid = {38632300}, issn = {2045-2322}, support = {JP23H02626//JSPS KAKENHI/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology ; Phase Transition ; *RNA-Binding Protein FUS/genetics/metabolism ; *Sarcoma ; }, abstract = {Intracellular aggregation of fused in sarcoma (FUS) is associated with the pathogenesis of familial amyotrophic lateral sclerosis (ALS). Under stress, FUS forms liquid droplets via liquid-liquid phase separation (LLPS). Two types of wild-type FUS LLPS exist in equilibrium: low-pressure LLPS (LP-LLPS) and high-pressure LLPS (HP-LLPS); the former dominates below 2 kbar and the latter over 2 kbar. Although several disease-type FUS variants have been identified, the molecular mechanism underlying accelerated cytoplasmic granule formation in ALS patients remains poorly understood. Herein, we report the reversible formation of the two LLPS states and the irreversible liquid-solid transition, namely droplet aging, of the ALS patient-type FUS variant R495X using fluorescence microscopy and ultraviolet-visible absorption spectroscopy combined with perturbations in pressure and temperature. Liquid-to-solid phase transition was accelerated in the HP-LLPS of R495X than in the wild-type variant; arginine slowed the aging of droplets at atmospheric conditions by inhibiting the formation of HP-LLPS more selectively compared to that of LP-LLPS. Our findings provide new insight into the mechanism by which R495X readily forms cytoplasmic aggregates. Targeting the aberrantly formed liquid droplets (the HP-LLPS state) of proteins with minimal impact on physiological functions could be a novel therapeutic strategy for LLPS-mediated protein diseases.}, } @article {pmid38631798, year = {2024}, author = {Gerecht, RB and Nable, JV}, title = {Out-of-Hospital Cardiac Arrest.}, journal = {Cardiology clinics}, volume = {42}, number = {2}, pages = {317-331}, doi = {10.1016/j.ccl.2024.02.014}, pmid = {38631798}, issn = {1558-2264}, mesh = {Humans ; *Out-of-Hospital Cardiac Arrest ; *Cardiopulmonary Resuscitation ; *Emergency Medical Services ; }, abstract = {Survival from out-of-hospital cardiac arrest (OHCA) is predicated on a community and system-wide approach that includes rapid recognition of cardiac arrest, capable bystander CPR, effective basic and advanced life support (BLS and ALS) by EMS providers, and coordinated postresuscitation care. Management of these critically ill patients continues to evolve. This article focuses on the management of OHCA by EMS providers.}, } @article {pmid38631307, year = {2024}, author = {Büssing, A and Recchia, DR and Ortiz, M}, title = {[Validierung eines Fragebogeninstrumentes zur Erfassung des Erlebens von Natur: Die Experience of Nature Scale].}, journal = {Complementary medicine research}, volume = {31}, number = {4}, pages = {309-318}, doi = {10.1159/000538807}, pmid = {38631307}, issn = {2504-2106}, mesh = {Humans ; Surveys and Questionnaires/standards ; Female ; Male ; Cross-Sectional Studies ; Adult ; Middle Aged ; Reproducibility of Results ; *Nature ; Psychometrics ; Aged ; Young Adult ; Adolescent ; }, abstract = {UNLABELLED: Hintergrund: In den letzten Jahren ist insbesondere die Natur als Ressource in das Interesse der gesundheitspsychologischen Forschung gerückt. In Ergänzung zum etablierten Konzept der Naturzuwendung als Haltung wurde ein For-schungsinstrument zum Naturerleben entwickelt, welches das subjektive, teilweise intentionale Erleben von Natur unter unterschiedlichen Aspekten beleuchtet. Dazu gehören insbesondere Natur als Erlebensraum, um sich von der Alltagsbelastung distanzieren zu können, um Auszeiten durch Ruhe und Stille finden zu können, um emotionale Ausgeglichenheit zu erlangen, Natur als Ort der Faszination und des Staunens, Naturerleben als Basis für einen verantwortlichen Umgang mit der Natur. Das Manuskript zeigt die Ergebnisse der Validierung des neu entwickelten Fragebogeninstrumentes zum Naturerleben. Methoden: Eine anonyme Online-Querschnittsstudie unter 441 Teilnehmenden wurde mit standardisierten Fragebogeninstrumenten zur Validie-rung der Experience of Nature Scale (ENS) mittels explorativer Faktoren- (Hauptkomponentenanalyse mit Varimax-Rotation) und Reliabilitätsanalysen (Cronbachs α) durchgeführt. Ergebnisse: Die explorative Faktorenanalyse der Naturerlebens-Skala mit 11 Items ergab drei Hauptfaktoren mit guter interner Kongruenz, die 71% der Varianz erklären: (1) Alltagsdistanzierung/Entspannung (Cronbachs α = 0,87), (2) Faszination Natur/Staunen (Cronbachs α = 0,82) und (3) Verantwortungsempfinden für Natur (Cronbachs α = 0,85). Diese Faktoren korrelierten stark mit der Naturverbundenheit (NR-6) und moderat bis stark mit Ehrfurcht/Dankbarkeit (GrAw-7) im Sinne der Konvergenzvalidität, aber nur marginal bis schwach mit psychologischem Wohlbefinden (WHO-5). Schlussfolgerungen: Die ENS zur Erfassung des affektiven Erlebens von Natur hat gute psychometrische Qua-litätsindizes und kann in künftigen Studien zur Bedeutung dieses Erlebens von Natur zum Beispiel als Prädiktor- oder Prozessvariable eingesetzt werden.

BACKGROUND: In recent years, nature as a resource in particular has become of interest in health psychology research. In addition to the established concept of nature-relatedness as an attitude, a research instrument was developed that focuses on the subjective experience of nature in different aspects. This includes nature as an area for experiencing, to distance oneself from the stress of everyday life, to find times for peace and quietness, as a place of fascination and amazement, resulting in greater emotional balance, and experiencing nature as a basis for a responsible approach to nature. Therefore, the newly developed instrument to assess nature experiences should be validated in a cohort of healthy volunteers.

METHODS: We conducted an anonymous cross-sectional analysis among 441 participants with standardized instruments to validate the Experience of Nature Scale (ENS) using exploratory factor analysis (principal component analysis with Varimax rotation) and reliability analysis (Cronbach’s α).

RESULTS: The exploratory factor analysis of the 11-item ENS revealed three main factors with good internal congruence, explaining 71% of the variance: (1) detachment from everyday life/relaxation (Cronbach’s α = 0.87), (2) fascination with nature/wondering (Cronbach’s α = 0.82), and (3) sense of responsibility for nature (Cronbach’s α = 0.85). In terms of convergent validity, the three factors correlated strongly with nature-relatedness (NR-6) and moderately to strongly with awe/gratitude (GrAw-7), but only marginally to weakly with psychological well-being (WHO-5).

CONCLUSIONS: The ENS for assessing the affective experience of nature shows good psychometric quality indices and could be used as a predictor and process variable in future studies addressing the meaning of this experience of nature.}, } @article {pmid38630299, year = {2024}, author = {Wolff, A and Demleitner, AF and Feneberg, E and Lingor, P}, title = {[Smell the smoke before one sees the fire-The oligosymptomatic prodromal phase of neurodegenerative diseases].}, journal = {Der Nervenarzt}, volume = {95}, number = {8}, pages = {689-696}, pmid = {38630299}, issn = {1433-0407}, mesh = {*Neurodegenerative Diseases/diagnosis ; *Prodromal Symptoms ; Humans ; *Early Diagnosis ; *Biomarkers/blood ; Disease Progression ; }, abstract = {BACKGROUND: With the increasing development of disease-modifying causative treatment, the importance of early diagnosis and detection of asymptomatic or oligosymptomatic early stages of neurodegenerative diseases is increasing.

OBJECTIVE: Presentation of early stages of neurodegenerative diseases, diagnostic procedures for the early detection and possible treatment consequences.

MATERIAL AND METHODS: Selective literature search, discussion of basic research and expert recommendations.

RESULTS: Many neurodegenerative diseases have a prodromal phase preceding the manifest disease that can be diagnosed with current criteria. In this prodromal phase, those affected are often oligosymptomatic but in some cases can already be identified using biomarkers. These developments are already taken into account in diagnostic criteria for some of these prodromal phases. The prodromal phase, in turn, is preceded by an asymptomatic phase which, however, already shows molecular changes and can be identified by biomarkers in some diseases. The early identification and stratification of patients is particularly important when planning studies for disease-modifying treatment, and biomarkers are already being used in clinical trials for this purpose.

DISCUSSION: Biomarker-based identification of individuals in the prodromal phase of neurodegenerative diseases is already possible for some entities. People who show the first signs of a neurodegenerative disease can be referred to centers for clinical trials and observational studies.}, } @article {pmid38628839, year = {2023}, author = {Uzunoglu-Ozyurek, E and Önal, G and Dökmeci, S}, title = {Investigating the Therapeutics Effects of Oral Cavity Derived Stem Cells on Neurodegenerative Diseases: A Systematic Review.}, journal = {Basic and clinical neuroscience}, volume = {14}, number = {5}, pages = {565-584}, pmid = {38628839}, issn = {2008-126X}, abstract = {INTRODUCTION: Published data obtained from in vitro and in vivo studies was reviewed systematically and analyzed critically to evaluate the effect of oral cavity-derived stem cells (OCDSCs) on the recovery or therapy of neurodegenerative diseases (NDs), such as Alzheimer disease (AD), amyotrophic lateral sclerosis (ALS), Huntington (HD) diseases, and Parkinson disease (PD).

METHODS: An electronic search was accomplished. References of included articles were also manually searched. Studies were critically evaluated for suitability against the inclusion/exclusion criteria and the data was extracted. Bias risk evaluation of the studies and evidence synthesis were conducted.

RESULTS: A total of 14 in vivo and 10 in vitro studies met the inclusion criteria. PD was induced in 10 in vivo and 7 in vitro studies, while AD was induced in 2 in vivo and 4 in vitro studies. Two studies (1 in vitro and 1 in vivo) evaluated ALS disease and 1 in vivo study evaluated HD. Moderate evidence was found for in vitro studies reporting the positive effect of OCDSCs on PD or AD recovery. Strong evidence was found for in vivo studies in which PD animal models were used; meanwhile, moderate evidence was found for the impact of OCDSCs on AD recovery. Limited evidence was found for in vivo studies evaluating HD and ALS.

CONCLUSION: Although studies reported favorable data regarding the OCDSCs on NDs, they presented a considerable risk of bias. Because of heterogeneous study characteristics, the current study recommends improving standardized methods to evaluate the therapeutic effects of OCDSCs on the NDs.}, } @article {pmid38628797, year = {2024}, author = {Sabnis, RW}, title = {Novel Isoxazolidines as RIPK1 Inhibitors for Treating Alzheimer's Disease, Multiple Sclerosis, and Amyotrophic Lateral Sclerosis.}, journal = {ACS medicinal chemistry letters}, volume = {15}, number = {4}, pages = {447-448}, pmid = {38628797}, issn = {1948-5875}, abstract = {Provided herein are novel isoxazolidines as RIPK1 inhibitors, pharmaceutical compositions, use of such compounds in treating Alzheimer's disease, multiple sclerosis, and amyotrophic lateral sclerosis (ALS), and processes for preparing such compounds.}, } @article {pmid38628764, year = {2024}, author = {Zhao, T and Duan, S and Li, J and Zheng, H and Liu, C and Zhang, H and Luo, H and Xu, Y}, title = {Mapping of repeat-associated non-AUG (RAN) translation knowledge: A bibliometric analysis.}, journal = {Heliyon}, volume = {10}, number = {8}, pages = {e29141}, pmid = {38628764}, issn = {2405-8440}, abstract = {Over 50 genetic human disorders are attributed to the irregular expansion of microsatellites. These expanded microsatellite sequences can experience bidirectional transcription, leading to new reading frames. Beyond the standard AUG initiation or adjacent start codons, they are translated into proteins characterized by disease-causing amino acid repeats through repeat-associated non-AUG translation. Despite its significance, there's a discernible gap in comprehensive and objective articles on RAN translation. This study endeavors to evaluate and delineate the contemporary landscape and progress of RAN translation research via a bibliometric analysis. We sourced literature on RAN translation from the Web of Science Core Collection. Utilizing two bibliometric analysis tools, CiteSpace and VOSviewer, we gauged individual impacts and interactions by examining annual publications, journals, co-cited journals, countries/regions, institutions, authors, and co-cited authors. Following this, we assessed the co-occurrence and bursts of keywords and co-cited references to pinpoint research hotspots and trending in RAN translation. Between 2011 and 2022, 1317 authors across 359 institutions from 34 countries/regions contributed to 250 publications on RAN translation, spread across 118 academic journals. This article presents a systematic, objective, and comprehensive analysis of the current literature on RAN translation. Our findings emphasize that mechanisms related to C9orf72 ALS/FTD are pivotal topics in the realm of RAN translation, with cellular stress and the utilization of small molecule marking the trending research areas.}, } @article {pmid38628040, year = {2025}, author = {Howard, J and Forrest Keenan, K and Mazanderani, F and Turner, MR and Locock, L}, title = {Experiences of predictive genetic testing in inherited motor neuron disease: Findings from a qualitative interview study.}, journal = {Journal of genetic counseling}, volume = {34}, number = {1}, pages = {e1904}, pmid = {38628040}, issn = {1573-3599}, support = {Locock/Sept19/941-794/MNDA_/Motor Neurone Disease Association/United Kingdom ; //University of Aberdeen/ ; }, mesh = {Humans ; *Motor Neuron Disease/genetics/diagnosis/psychology ; *Genetic Testing ; Female ; Male ; Middle Aged ; Adult ; Qualitative Research ; Interviews as Topic ; Aged ; }, abstract = {Predictive genetic testing is increasingly available for individuals with a heightened risk of motor neuron disease (MND). However, little is known about how they decide whether or not to get tested, and how they experience this process. This paper reports findings from a constructivist grounded theory-informed interview study with 24 family members of people with identified or suspected inherited MND (iMND). Fourteen did not know their genetic status, and nine had decided to have predictive testing, of whom six tested positive for the pathogenic gene variant identified in their family and three tested negative. One additional person was identified as negative through a parent's negative result. This paper explores the diverse ways people approached testing, and the many factors and motivations involved, based on personal attitudes and goals, experiences of living with genetic risk, and wider family considerations and circumstances. Results were met with a range of emotions; whatever the outcome, the news disrupted each person's view of the future, and they adapted in their own way and time. Support after results was variable and a perceived lack of support impacted coping and the ability to move forwards. This paper situates findings against literature on other genetic conditions, highlighting experiences as grounded in the unique characteristics of iMND. Thus, it emphasizes the need for disease-specific guidelines and support structures around predictive genetic testing in this context. Understanding people's experiences and responding to these needs is particularly timely given the uptake of testing amongst this group is anticipated to rise with increasing access to genetic testing for people with MND, and gene-specific clinical trials.}, } @article {pmid38627418, year = {2024}, author = {Bales, I and Zhang, H}, title = {A six degrees-of-freedom cable-driven robotic platform for head-neck movement.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {8750}, pmid = {38627418}, issn = {2045-2322}, support = {2240508//National Science Foundation/ ; }, mesh = {Humans ; *Robotics/methods ; *Robotic Surgical Procedures ; Movement/physiology ; Head Movements/physiology ; *Exoskeleton Device ; *Nervous System Diseases ; }, abstract = {This paper introduces a novel cable-driven robotic platform that enables six degrees-of-freedom (DoF) natural head-neck movements. Poor postural control of the head-neck can be a debilitating symptom of neurological disorders such as amyotrophic lateral sclerosis and cerebral palsy. Current treatments using static neck collars are inadequate, and there is a need to develop new devices to empower movements and facilitate physical rehabilitation of the head-neck. State-of-the-art neck exoskeletons using lower DoF mechanisms with rigid linkages are limited by their hard motion constraints imposed on head-neck movements. By contrast, the cable-driven robot presented in this paper does not constrain motion and enables wide-range, 6-DoF control of the head-neck. We present the mechatronic design, validation, and control implementations of this robot, as well as a human experiment to demonstrate a potential use case of this versatile robot for rehabilitation. Participants were engaged in a target reaching task while the robot applied both assistive and resistive moments on the head during the task. Our results show that neck muscle activation increased by 19% when moving the head against resistance and decreased by 28-43% when assisted by the robot. Overall, these results provide a scientific justification for further research in enabling movement and identifying personalized rehabilitation for motor training. Beyond rehabilitation, other applications such as applying force perturbations on the head to study sensory integration and applying traction to achieve pain relief may benefit from the innovation of this robotic platform which is capable of applying controlled 6-DoF forces/moments on the head.}, } @article {pmid38627359, year = {2024}, author = {Magrì, A and Lipari, CLR and Caccamo, A and Battiato, G and Conti Nibali, S and De Pinto, V and Guarino, F and Messina, A}, title = {AAV-mediated upregulation of VDAC1 rescues the mitochondrial respiration and sirtuins expression in a SOD1 mouse model of inherited ALS.}, journal = {Cell death discovery}, volume = {10}, number = {1}, pages = {178}, pmid = {38627359}, issn = {2058-7716}, abstract = {Mitochondrial dysfunction represents one of the most common molecular hallmarks of both sporadic and familial forms of amyotrophic lateral sclerosis (ALS), a neurodegenerative disorder caused by the selective degeneration and death of motor neurons. The accumulation of misfolded proteins on and within mitochondria, as observed for SOD1 G93A mutant, correlates with a drastic reduction of mitochondrial respiration and the inhibition of metabolites exchanges, including ADP/ATP and NAD[+]/NADH, across the Voltage-Dependent Anion-selective Channel 1 (VDAC1), the most abundant channel protein of the outer mitochondrial membrane. Here, we show that the AAV-mediated upregulation of VDAC1 in the spinal cord of transgenic mice expressing SOD1 G93A completely rescues the mitochondrial respiratory profile. This correlates with the increased activity and levels of key regulators of mitochondrial functions and maintenance, namely the respiratory chain Complex I and the sirtuins (Sirt), especially Sirt3. Furthermore, the selective increase of these mitochondrial proteins is associated with an increase in Tom20 levels, the receptor subunit of the TOM complex. Overall, our results indicate that the overexpression of VDAC1 has beneficial effects on ALS-affected tissue by stabilizing the Complex I-Sirt3 axis.}, } @article {pmid38627298, year = {2024}, author = {Hamad, AA and Amer, BE}, title = {Safety of masitinib in patients with neurodegenerative diseases: a meta-analysis of randomized controlled trials.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {45}, number = {7}, pages = {3503-3507}, pmid = {38627298}, issn = {1590-3478}, mesh = {Humans ; *Randomized Controlled Trials as Topic ; *Thiazoles/adverse effects/administration & dosage/therapeutic use ; *Neurodegenerative Diseases/drug therapy ; *Piperidines/adverse effects/therapeutic use/administration & dosage ; *Benzamides/adverse effects/administration & dosage ; *Pyridines/adverse effects/administration & dosage/therapeutic use ; Protein Kinase Inhibitors/adverse effects/administration & dosage ; }, abstract = {OBJECTIVES: This meta-analysis aimed to examine the safety of masitinib in patients with neurodegenerative diseases.

METHODS: We considered randomized controlled trials (RCTs) comparing different doses of masitinib versus placebo. We performed our analysis using the R (v.4.3.0) programming language and the incidence of adverse events was pooled using risk ratio (RR) and 95% confidence interval (CI).

RESULTS: We included five RCTs, focusing on multiple sclerosis (MS), Alzheimer's disease (AD), and amyotrophic lateral sclerosis. The meta-analysis revealed a significantly higher incidence of adverse events in the masitinib group compared to the control group, regardless of adverse event grade and masitinib dose (RR = 1.12, 95% CI [1.07 to 1.17], P < 0.01). Adverse events categorized as severe, non-fatal serious, leading to dose reduction, and leading to permanent discontinuation also showed a higher incidence in the masitinib group (P ≤ 0.01). Subgroup analysis for AD and MS supported these findings. The pooled incidence of adverse events, regardless of their grade, was higher in the masitinib group for both the 3 mg/kg/d dose (RR = 1.13, P = 0.01) and the 4.5 mg/kg/d dose (RR = 1.11, P < 0.01). However, there was no significant difference between masitinib 3 mg/kg/d dose and placebo regarding severe and non-fatal serious adverse events for the.

CONCLUSION: Masitinib use in neurodegenerative diseases presents safety concerns that may impact patients' quality of life and require management. Further research is recommended to determine the optimal dose with minimal safety concerns in this patient population.}, } @article {pmid38627230, year = {2024}, author = {Taufik, SA and Ramli, N and Tan, AH and Lim, SY and Ghani, MTA and Shahrizaila, N}, title = {Longitudinal Changes in the Retinal Nerve Fiber Layer Thickness in Amyotrophic Lateral Sclerosis and Parkinson's Disease.}, journal = {Journal of clinical neurology (Seoul, Korea)}, volume = {20}, number = {3}, pages = {285-292}, pmid = {38627230}, issn = {1738-6586}, abstract = {BACKGROUND AND PURPOSE: There is increasing evidence that the anterior visual pathways are involved in neurodegenerative diseases including amyotrophic lateral sclerosis (ALS) and Parkinson's disease (PD). This study investigated longitudinal changes in retinal nerve fiber layer (RNFL) thickness in patients with ALS and PD with the aim of better understanding their roles as biomarkers of disease progression.

METHODS: This study recruited 21 ALS patients, 19 age-matched PD patients, and 21 agematched healthy controls. Patient demographics and clinical scores relating to the respective diseases were documented. The RNFL thickness was measured using optical coherence tomography at baseline and after 6 months.

RESULTS: At baseline, the RNFL in the superior quadrant was significantly thinner in the patients with ALS than in healthy controls (109.90±22.41 µm vs. 127.81±17.05 µm [mean±standard deviation], p=0.008). The RNFL thickness did not differ significantly between the ALS and PD patients or between the PD patients and healthy controls. At 6 months, there was further significant RNFL thinning in patients with ALS, for both the overall thickness (baseline: median=94.5 µm, range=83.0-106.0 µm; follow-up: median=93.5 µm, range=82.5-104.5 µm, p=0.043) and the thickness in the inferior quadrant (median=126 µm, range=109.5-142.5 µm; and median=117.5 µm, range=98.5-136.5 µm; respectively, p=0.032). However, these changes were not correlated with the ALS functional scores. In contrast, the patients with PD did not demonstrate a significant change in RNFL thickness between the two time points.

CONCLUSIONS: The RNFL thickness is a promising biomarker of disease progression in patients with ALS but not in those with PD, which has a slower disease progression.}, } @article {pmid38626361, year = {2024}, author = {Murdock, BJ and Zhao, B and Pawlowski, KD and Famie, JP and Piecuch, CE and Webber-Davis, IF and Teener, SJ and Feldman, EL and Zhao, L and Goutman, SA}, title = {Peripheral Immune Profiles Predict ALS Progression in an Age- and Sex-Dependent Manner.}, journal = {Neurology(R) neuroimmunology & neuroinflammation}, volume = {11}, number = {3}, pages = {e200241}, pmid = {38626361}, issn = {2332-7812}, support = {R01 TS000327/TS/ATSDR CDC HHS/United States ; U54 NS092091/NS/NINDS NIH HHS/United States ; K23 ES027221/ES/NIEHS NIH HHS/United States ; UL1 TR002240/TR/NCATS NIH HHS/United States ; R01 NS120926/NS/NINDS NIH HHS/United States ; R01 NS127188/NS/NINDS NIH HHS/United States ; R01 ES030049/ES/NIEHS NIH HHS/United States ; R21 NS102960/NS/NINDS NIH HHS/United States ; }, mesh = {Male ; Humans ; Female ; *Amyotrophic Lateral Sclerosis ; *Neurodegenerative Diseases ; Disease Progression ; Prognosis ; Biomarkers ; }, abstract = {BACKGROUND AND OBJECTIVES: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease whose pathobiology associates with peripheral blood immune cell levels and activation patterns in an age and sex-dependent manner. This study's objective was to identify immune profile associations with ALS progression, whether the associations are age and sex-specific, and whether immune profiles can predict a future disease course.

METHODS: Flow cytometry immune profiles (a combination of 22 peripheral blood immune markers) were generated for 241 participants with ALS and linked to ALS progression, using progression-free survival, which is a composite combining the revised ALS Functional Rating Scale and survival. Participants were first grouped by immune profiles using unsupervised hierarchical clustering, and clusters were associated with subsequent progression-free survival. Next, individual immune markers were associated with progression-free survival using least absolute shrinkage and selection operator-Cox regression. Analyses were stratified by age and sex to identify demographic-specific immune mechanisms. Finally, random forest determined the predictive power of immune profiles on ALS progression in the whole population and again stratified by age and sex.

RESULTS: Progression-free survival differed between clusters of participants with similar immune profiles, particularly reduced natural killer (NK)-cell activation associated with slower progression. Individual markers such as neutrophil levels and NK-cell NKp46 expression associated with faster ALS progression while overall NK-cell levels and NK-cell subpopulations associated with slower progression; the strength of these associations varied by age and sex. Adding these immune markers to prediction models dramatically increased short-term prediction compared with routine clinical prognostic variables alone, and the addition of NK-cell markers further improved the prediction accuracy in female participants.

DISCUSSION: Specific immune profiles likely contribute to ALS progression in an age and sex-dependent manner, and peripheral immune markers enhance the prediction of short-term clinical outcomes. These findings suggest a complex milieu of immune profiles associated with ALS progression, and more detailed immunophenotyping in ALS will facilitate personalized immunotherapeutics in ALS.}, } @article {pmid38625841, year = {2024}, author = {Savant, R and Pradhan, RK and Bhagat, S and Mythri, RB and Varghese, AM and Vengalil, S and Nalini, A and Sathyaprabha, TN and Raju, TR and Vijayalakshmi, K}, title = {Enhanced levels of fractalkine and HSP60 in cerebrospinal fluid of sporadic amyotrophic lateral sclerosis patients.}, journal = {The International journal of neuroscience}, volume = {}, number = {}, pages = {1-11}, doi = {10.1080/00207454.2024.2344581}, pmid = {38625841}, issn = {1563-5279}, abstract = {Amyotrophic Lateral Sclerosis (ALS) is a multifactorial neurodegenerative disorder with a significant contribution of non-cell autonomous mechanisms to motor neuronal degeneration. Amongst a plethora of molecules, fractalkine (C-X3-C motif chemokine ligand 1), and Heat Shock Protein 60 (HSP60), are key modulators of microglial activation. The contribution of these molecules in Sporadic ALS (SALS) remains unexplored. To investigate this, fractalkine levels were estimated in Cerebrospinal fluid (CSF) of SALS patients (ALS-CSF; n = 44) by Enzyme-linked Immunosorbent Assay (ELISA) and correlated with clinical parameters including disease severity and duration. CSF HSP60 levels were estimated by Western blotting (ALS-CSF; n = 19). Also, CSF levels of Chitotriosidase-1 (CHIT-1), a microglia-specific neuroinflammatory molecule, were measured and its association, if any, with fractalkine and HSP60 was investigated. Both fractalkine and HSP60 levels were significantly elevated in ALS-CSF. Similar to our earlier observation, CHIT-1 levels were also upregulated. Fractalkine showed a moderate negative correlation with the ALS-Functional Rating Scale (ALSFRS) score indicating its significant rise in mild cases which plateaued in cases with high disease severity. However, no obvious correlation was found between fractalkine, HSP60, and CHIT-1. Our study hints that high fractalkine levels in mild cases might be conferring neuroprotection by combating microglial activation and highlights its importance as a novel therapeutic target for SALS. On the other hand, significantly enhanced levels of HSP60, a pro-inflammatory molecule, hint towards its role in accentuating microgliosis, although, it doesn't act synergistically with CHIT-1. Our study suggests that fractalkine and HSP60 act independently of CHIT-1 to suppress and accentuate neuroinflammation, respectively.}, } @article {pmid38625649, year = {2024}, author = {Chen, L and Ye, S and Murphy, D and Wu, J and Zhang, H and Liu, H and Zou, B and Hou, G and Zhang, N and Yin, T and Smith, RA and Fan, D}, title = {Chinese Translation and Validation of the Center for Neurologic Study Lability Scale.}, journal = {Neurology and therapy}, volume = {13}, number = {3}, pages = {739-747}, pmid = {38625649}, issn = {2193-8253}, support = {81873784//National Natural Science Foundation of China/ ; 82071426//National Natural Science Foundation of China/ ; }, abstract = {INTRODUCTION: Pseudobulbar palsy is a common symptom in patients with amyotrophic lateral sclerosis (ALS), but it is often underdiagnosed or misdiagnosed as other diseases. The Center for Neurologic Study Lability Scale (CNS-LS) is a self-report scale consisting of seven questions designed for evaluating pseudobulbar affect (PBA). The current study aimed to validate a Chinese version of the CNS-LS.

METHODS: The Chinese version of the CNS-LS was obtained through a standardized forward-backward translation and cultural adaptation. A total of 105 patients with ALS were recruited from the ALS database of Peking University Third Hospital in Beijing, China, to complete the CNS-LS. The reliability of the Chinese version was determined by the test-retest method, and receiver operating characteristic (ROC) analysis was performed for criterion validity.

RESULTS: Of 105 patients with ALS, 37 had symptoms of PBA and were diagnosed with that condition by neurologists. Forty-two patients completed the CNS-LS twice, and there was no statistically significant difference between the scores (Z = -0.896, p = 0.37). The Spearman correlation coefficient between the test and retest scores was 0.940 (p < 0.0005), and the Cronbach alpha coefficient was high (α = 0.905, n = 105). Scores of 12 or higher on the CNS-LS identified PBA with sensitivity of 0.919 and specificity of 0.882. The area under the ROC curve was 0.924.

CONCLUSION: The Chinese version of the CNS-LS demonstrated good sensitivity and specificity in the group of patients with ALS enrolled in this study. The CNS-LS should be a useful instrument for clinical and research purposes for patients in this language group.}, } @article {pmid38625400, year = {2024}, author = {Barel, D and Marom, D and Ponger, P and Kurolap, A and Bar-Shira, A and Kaplan-Ber, I and Mory, A and Abramovich, B and Yaron, Y and Drory, V and Baris Feldman, H}, title = {Genetic diagnosis and detection rates using C9orf72 repeat expansion and a multi-gene panel in amyotrophic lateral sclerosis.}, journal = {Journal of neurology}, volume = {271}, number = {7}, pages = {4258-4266}, pmid = {38625400}, issn = {1432-1459}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/diagnosis/epidemiology ; *C9orf72 Protein/genetics ; Middle Aged ; Male ; Female ; *DNA Repeat Expansion/genetics ; Aged ; *Genetic Testing ; Israel/epidemiology ; Jews/genetics ; Adult ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder. It is mostly sporadic, with the C9orf72 repeat expansion being the most common genetic cause. While the prevalence of C9orf72-ALS in patients from different populations has been studied, data regarding the yield of C9orf72 compared to an ALS gene panel testing is limited.We aimed to explore the application of C9orf72 versus a gene panel in the general Israeli population. A total of 140 ALS patients attended our Neurogenetics Clinic throughout 2018-2023. Disease onset was between ages 60 and 69 years for most patients (34%); however, a quarter had an early-onset disease (< 50 years). Overall, 119 patients (85%) were genetically evaluated: 116 (97%) were tested for the C9orf72 repeat expansion and 64 (54%) underwent gene panel testing. The C9orf72 repeat expansion had a prevalence of 21% among Ashkenazi Jewish patients compared to 5.7% in non-Ashkenazi patients, while the gene panel had a higher yield in non-Ashkenazi patients with 14% disease-causing variants compared to 5.7% in Ashkenazi Jews. Among early-onset ALS patients, panel testing was positive in 12% compared to 2.9% for C9orf72.We suggest a testing strategy for the Israeli ALS patients: C9orf72 should be the first-tier test in Ashkenazi Jewish patients, while a gene panel should be considered as the first step in non-Ashkenazi and early-onset patients. Tiered testing has important implications for patient management, including prognosis, ongoing clinical trials, and prevention in future generations. Similar studies should be implemented worldwide to uncover the diverse ALS genetic architecture and facilitate tailored care.}, } @article {pmid38623842, year = {2024}, author = {Kaul, CM and Haller, M and Yang, J and Solomon, S and Khan, MR and Pitts, RA and Phillips, MS}, title = {The authors' reply to Jensen et al's Letter to the Editor.}, journal = {Infection control and hospital epidemiology}, volume = {45}, number = {6}, pages = {799-800}, doi = {10.1017/ice.2024.59}, pmid = {38623842}, issn = {1559-6834}, } @article {pmid38623278, year = {2024}, author = {Inci, OK and Basırlı, H and Can, M and Yanbul, S and Seyrantepe, V}, title = {Gangliosides as Therapeutic Targets for Neurodegenerative Diseases.}, journal = {Journal of lipids}, volume = {2024}, number = {}, pages = {4530255}, pmid = {38623278}, issn = {2090-3030}, abstract = {Gangliosides, sialic acid-containing glycosphingolipids, are abundant in cell membranes and primarily involved in controlling cell signaling and cell communication. The altered ganglioside pattern has been demonstrated in several neurodegenerative diseases, characterized during early-onset or infancy, emphasizing the significance of gangliosides in the brain. Enzymes required for the biosynthesis of gangliosides are linked to several devastating neurological disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), hereditary spastic paraplegia (HSP). In this review, we summarized not only the critical roles of biosynthetic enzymes and their inhibitors in ganglioside metabolism but also the efficacy of treatment strategies of ganglioside to address their significance in those diseases.}, } @article {pmid38622643, year = {2024}, author = {Filipe, CB and Carreira, NR and Reis-Pina, P}, title = {Optimizing breathlessness management in amyotrophic lateral sclerosis: insights from a comprehensive systematic review.}, journal = {BMC palliative care}, volume = {23}, number = {1}, pages = {100}, pmid = {38622643}, issn = {1472-684X}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/complications/therapy ; *Dyspnea/etiology/therapy ; Palliative Care/methods/standards ; Noninvasive Ventilation/methods/standards ; Quality of Life ; Analgesics, Opioid/therapeutic use ; }, abstract = {BACKGROUND: Breathlessness is a prevalent symptom affecting the quality of life (QOL) of Amyotrophic Lateral Sclerosis (ALS) patients. This systematic review explored the interventions for controlling breathlessness in ALS patients, emphasizing palliative care (PALC), non-invasive ventilation (NIV), opioids, and non-pharmacological strategies.

METHODS: A comprehensive search of PubMed, Cochrane Library, and Web of Science databases was conducted. Eligibility criteria encompassed adults with ALS or motor neuron disease experiencing breathlessness. Outcomes included QOL and symptom control. Study designs comprised qualitative studies, cohort studies, and randomized controlled trials.

RESULTS: Eight studies were included, most exhibiting low bias risk, comprising one randomized controlled trial, three cohort studies, two comparative retrospective studies, and two qualitative studies (interviews). Most studies originated from Europe, with one from the United States of America. The participants totaled 3423, with ALS patients constituting 95.6%. PALC consultations significantly improved symptom assessment, advance care planning, and discussions about goals of care. NIV demonstrated efficacy in managing breathlessness, with considerations for device limitations. Opioids were effective, though predominantly studied in non-ALS patients. Non-pharmacological strategies varied in efficacy among patients.

CONCLUSION: The findings underscore the need for individualized approaches in managing breathlessness in ALS. PALC, NIV, opioids, and non-pharmacological strategies each play a role, with unique considerations. Further research, especially ALS-specific self-management studies, is warranted.}, } @article {pmid38621750, year = {2024}, author = {Kosmachevskaya, OV and Novikova, NN and Yakunin, SN and Topunov, AF}, title = {Formation of Supplementary Metal-Binding Centers in Proteins under Stress Conditions.}, journal = {Biochemistry. Biokhimiia}, volume = {89}, number = {Suppl 1}, pages = {S180-S204}, doi = {10.1134/S0006297924140104}, pmid = {38621750}, issn = {1608-3040}, mesh = {*Metals/chemistry/metabolism ; *Oxidative Stress ; Oxidation-Reduction ; Protein Processing, Post-Translational ; }, abstract = {In many proteins, supplementary metal-binding centers appear under stress conditions. They are known as aberrant or atypical sites. Physico-chemical properties of proteins are significantly changed after such metal binding, and very stable protein aggregates are formed, in which metals act as "cross-linking" agents. Supplementary metal-binding centers in proteins often arise as a result of posttranslational modifications caused by reactive oxygen and nitrogen species and reactive carbonyl compounds. New chemical groups formed as a result of these modifications can act as ligands for binding metal ions. Special attention is paid to the role of cysteine SH-groups in the formation of supplementary metal-binding centers, since these groups are the main target for the action of reactive species. Supplementary metal binding centers may also appear due to unmasking of amino acid residues when protein conformation changing. Appearance of such centers is usually considered as a pathological process. Such unilateral approach does not allow to obtain an integral view of the phenomenon, ignoring cases when formation of metal complexes with altered proteins is a way to adjust protein properties, activity, and stability under the changed redox conditions. The role of metals in protein aggregation is being studied actively, since it leads to formation of non-membranous organelles, liquid condensates, and solid conglomerates. Some proteins found in such aggregates are typical for various diseases, such as Alzheimer's and Huntington's diseases, amyotrophic lateral sclerosis, and some types of cancer.}, } @article {pmid38621743, year = {2024}, author = {Rezvykh, A and Shteinberg, D and Bronovitsky, E and Ustyugov, A and Funikov, S}, title = {Animal Models of FUS-Proteinopathy: A Systematic Review.}, journal = {Biochemistry. Biokhimiia}, volume = {89}, number = {Suppl 1}, pages = {S34-S56}, doi = {10.1134/S0006297924140037}, pmid = {38621743}, issn = {1608-3040}, mesh = {Animals ; Humans ; *Amyotrophic Lateral Sclerosis/genetics ; RNA-Binding Protein FUS/genetics/metabolism ; Motor Neurons/metabolism/pathology ; Cytoplasm/metabolism ; Mutation ; Disease Models, Animal ; }, abstract = {Mutations that disrupt the function of the DNA/RNA-binding protein FUS could cause amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases. One of the key features in ALS pathogenesis is the formation of insoluble protein aggregates containing aberrant isoforms of the FUS protein in the cytoplasm of upper and lower motor neurons. Reproduction of human pathology in animal models is the main tool for studying FUS-associated pathology and searching for potential therapeutic agents for ALS treatment. In this review, we provide a systematic analysis of the role of FUS protein in ALS pathogenesis and an overview of the results of modelling FUS-proteinopathy in animals.}, } @article {pmid38621696, year = {2025}, author = {Müller, F and Proske, A and Füchtmeier, B and Wulbrand, C}, title = {Are Process Changes Measurable? An Analysis of 4136 Proximal Femur Fractures over 16 Year.}, journal = {Zeitschrift fur Orthopadie und Unfallchirurgie}, volume = {163}, number = {1}, pages = {27-34}, doi = {10.1055/a-2276-6440}, pmid = {38621696}, issn = {1864-6743}, mesh = {Humans ; Retrospective Studies ; Male ; Female ; Reoperation/statistics & numerical data ; Aged ; *Fracture Fixation, Internal/statistics & numerical data ; Trauma Centers ; Aged, 80 and over ; Middle Aged ; Germany/epidemiology ; *Hip Fractures/surgery/mortality ; Fracture Fixation, Intramedullary ; Postoperative Complications ; *Femoral Fractures/surgery ; Blood Transfusion/statistics & numerical data ; Adult ; Proximal Femoral Fractures ; }, abstract = {Prozessänderungen im perioperativen Setting werden selten analysiert, weil ihre Ergebnisse nicht unmittelbar fassbar sind und es einer hohen Fallzahl bedarf. Primäres Ziel war es, Prozessänderungen retrospektiv anhand proximaler Femurfrakturen (PF) zu evaluieren und deren Effekt mit verschiedenen Zielkriterien zu überprüfen. Sekundäres Ziel war die Definition möglicher Qualitätskriterien für die Versorgung von PF.Retrospektive Analyse der Datenbank eines Level-1-Traumazentrums zu PF. Eingeschlossen wurden alle osteosynthetisch und endoprothetisch versorgten PF im Behandlungszeitraum vom 01.01.2006 bis 31.12.2021. Der Zeitraum von 16 Jahren wurde für die Statistik trichotom aufgeteilt und die ersten 6 Jahre als Ausgangsbasis verwendet. Insgesamt 10 Prozessänderungen wurden in den folgenden 10 Jahren vorgenommen. Die Auswirkungen dieser Änderungen wurden anhand 1. der operativen Revisionsrate, 2. der Infektionsrate, 3. der perioperativen Transfusionsrate sowie 4. der 1-Jahres-Letalität überprüft.Insgesamt 4163 PF wurden analysiert. Hinsichtlich der Zielkriterien zeigten die Änderungen der ersten 5 Jahre (2012-2016; intramedulläres Verfahren für Osteosynthesen sowie Einwegabdeckung und Einwegkittel) den stärksten Effekt mit einer erstmaligen Senkung der operativen Revisionsrate unter 10% auf Dauer. Weitere Prozessoptimierungen der letzten 5 Jahre (2017-2021) erbrachten ebenfalls messbare Verbesserungen (Senkung der Infektions- und Transfusionsrate). Die 1-Jahres-Letalität blieb unverändert, auch während der COVID-19-Pandemie.Prozessänderungen bei PF führen nicht unmittelbar zu objektiv messbaren Verbesserungen. Rückblickend erscheint der Paradigmenwechsel von extra- auf intramedulläre Osteosynthese den höchsten Effekt erzielt zu haben, wenngleich über die letzten 10 Jahre eine schrittweise Besserung aller Zielkriterien eintrat - mit Ausnahme der Letalität. Als objektive Qualitätskontrolle sollte eine 1-Jahres-Revisionsrate unter 10% angestrebt sein.}, } @article {pmid38621442, year = {2024}, author = {Dewangan, D and Joshi, A and Padhi, AK}, title = {Long-timescale atomistic simulations uncover loss-of-function mechanisms of uncharacterized Angiogenin mutants associated with ALS.}, journal = {Archives of biochemistry and biophysics}, volume = {756}, number = {}, pages = {110000}, doi = {10.1016/j.abb.2024.110000}, pmid = {38621442}, issn = {1096-0384}, mesh = {*Ribonuclease, Pancreatic/chemistry/genetics/metabolism ; *Amyotrophic Lateral Sclerosis/genetics/metabolism ; Humans ; *Molecular Dynamics Simulation ; Loss of Function Mutation ; Molecular Docking Simulation ; Mutation ; Protein Conformation ; Thermodynamics ; }, abstract = {Amyotrophic Lateral Sclerosis (ALS) is a devastating neurodegenerative disease characterized by progressive degeneration of motor neurons, resulting in respiratory failure and mortality within 3-5 years. Mutations in the Angiogenin (ANG) cause loss of ribonucleolytic and nuclear translocation activities, contributing to ALS pathogenesis. This study focused on investigating two uncharacterized ANG mutations, T11S and R122H, newly identified in the Project Mine consortium. Using extensive computational analysis, including structural modeling and microsecond-timescale molecular dynamics (MD) simulations, we observed conformational changes in the catalytic residue His114 of ANG induced by T11S and R122H mutations. These alterations impaired ribonucleolytic activity, as inferred through molecular docking and binding free energy calculations. Gibbs free energy landscape and residue-residue interaction network analysis further supported our findings, revealing the energetic states and allosteric pathway from the mutated site to His114. Additionally, we assessed the binding of NCI-65828, an inhibitor of ribonucleolytic activity of ANG, and found reduced effectiveness in binding to T11S and R122H mutants when His114 assumed a non-native conformation. This highlights the crucial role of His114 and its association with ALS. Elucidating the relationship between physical structure and functional dynamics of frequently mutated ANG mutants is essential for understanding ALS pathogenesis and developing more effective therapeutic interventions.}, } @article {pmid38621131, year = {2024}, author = {Sachdev, A and Gill, K and Sckaff, M and Birk, AM and Aladesuyi Arogundade, O and Brown, KA and Chouhan, RS and Issagholian-Lewin, PO and Patel, E and Watry, HL and Bernardi, MT and Keough, KC and Tsai, YC and Smith, AST and Conklin, BR and Clelland, CD}, title = {Reversal of C9orf72 mutation-induced transcriptional dysregulation and pathology in cultured human neurons by allele-specific excision.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {121}, number = {17}, pages = {e2307814121}, pmid = {38621131}, issn = {1091-6490}, support = {K08 NS112330/NS/NINDS NIH HHS/United States ; U19 NS132303/NS/NINDS NIH HHS/United States ; TL1 TR001871/TR/NCATS NIH HHS/United States ; R01 HL130533/HL/NHLBI NIH HHS/United States ; RF1 AG072052/AG/NIA NIH HHS/United States ; R01 AG072052/AG/NIA NIH HHS/United States ; R03 TR004009/TR/NCATS NIH HHS/United States ; U01 NS134062/NS/NINDS NIH HHS/United States ; P01 HL146366/HL/NHLBI NIH HHS/United States ; }, mesh = {Humans ; C9orf72 Protein/genetics/metabolism ; Alleles ; *Amyotrophic Lateral Sclerosis/metabolism ; *Frontotemporal Dementia/metabolism ; Motor Neurons/metabolism ; Mutation ; DNA Repeat Expansion/genetics ; Dipeptides/metabolism ; }, abstract = {Efforts to genetically reverse C9orf72 pathology have been hampered by our incomplete understanding of the regulation of this complex locus. We generated five different genomic excisions at the C9orf72 locus in a patient-derived induced pluripotent stem cell (iPSC) line and a non-diseased wild-type (WT) line (11 total isogenic lines), and examined gene expression and pathological hallmarks of C9 frontotemporal dementia/amyotrophic lateral sclerosis in motor neurons differentiated from these lines. Comparing the excisions in these isogenic series removed the confounding effects of different genomic backgrounds and allowed us to probe the effects of specific genomic changes. A coding single nucleotide polymorphism in the patient cell line allowed us to distinguish transcripts from the normal vs. mutant allele. Using digital droplet PCR (ddPCR), we determined that transcription from the mutant allele is upregulated at least 10-fold, and that sense transcription is independently regulated from each allele. Surprisingly, excision of the WT allele increased pathologic dipeptide repeat poly-GP expression from the mutant allele. Importantly, a single allele was sufficient to supply a normal amount of protein, suggesting that the C9orf72 gene is haplo-sufficient in induced motor neurons. Excision of the mutant repeat expansion reverted all pathology (RNA abnormalities, dipeptide repeat production, and TDP-43 pathology) and improved electrophysiological function, whereas silencing sense expression did not eliminate all dipeptide repeat proteins, presumably because of the antisense expression. These data increase our understanding of C9orf72 gene regulation and inform gene therapy approaches, including antisense oligonucleotides (ASOs) and CRISPR gene editing.}, } @article {pmid38621087, year = {2024}, author = {Zhuang, Y and Wang, Y and Yang, X and Ma, T}, title = {Visible light positioning system using a smartphone's built-in ambient light sensor and inertial measurement unit.}, journal = {Optics letters}, volume = {49}, number = {8}, pages = {2105-2108}, doi = {10.1364/OL.519674}, pmid = {38621087}, issn = {1539-4794}, abstract = {In recent years, the visible light positioning field has experienced remarkable advancements. However, smartphones find it difficult to identify light-emitting diode (LED) and extract each LED's light signal intensity due to the low-frequency and uneven sampling of built-in ambient light sensors (ALS, which is a photodiode that measures ambient light in lux units). Thus, traditional visible light positioning systems cannot be directly applied to smartphones. In this Letter, we propose a single-light visible light positioning system using a non-modulated LED as an emitter, the built-in ALS as the receiver, and the inertial measurement unit of the smartphone to assist in measuring the smartphone's attitude. It only requires the user to turn the smartphone by a few angles in a stationary position to estimate its current three-dimensional (3D) spatial position. This method does not require modification of the existing lighting system and consumes less power than the camera-based visible light positioning (VLP) systems. We have built an experimental site measuring 5 m × 5 m × 2.2 m to evaluate the performance of the positioning system, and the preliminary results show that the proposed system achieves sub-meter-level positioning accuracy.}, } @article {pmid38617354, year = {2024}, author = {Lynch, EM and Pittman, S and Daw, J and Ikenaga, C and Chen, S and Dhavale, DD and Jackrel, ME and Ayala, YM and Kotzbauer, P and Ly, CV and Pestronk, A and Lloyd, TE and Weihl, CC}, title = {Seeding competent TDP-43 persists in human patient and mouse muscle.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {38617354}, issn = {2692-8205}, support = {F32 NS124841/NS/NINDS NIH HHS/United States ; K24 AR073317/AR/NIAMS NIH HHS/United States ; R01 AG031867/AG/NIA NIH HHS/United States ; }, abstract = {TAR DNA-binding protein 43 (TDP-43) is an RNA binding protein that accumulates as aggregates in the central nervous system of some neurodegenerative diseases. However, TDP-43 aggregation is also a sensitive and specific pathologic feature found in a family of degenerative muscle diseases termed inclusion body myopathy (IBM). TDP-43 aggregates from ALS and FTD brain lysates may serve as self-templating aggregate seeds in vitro and in vivo, supporting a prion-like spread from cell to cell. Whether a similar process occurs in IBM patient muscle is not clear. We developed a mouse model of inducible, muscle-specific cytoplasmic localized TDP-43. These mice develop muscle weakness with robust accumulation of insoluble and phosphorylated sarcoplasmic TDP-43, leading to eosinophilic inclusions, altered proteostasis and changes in TDP-43-related RNA processing that resolve with the removal of doxycycline. Skeletal muscle lysates from these mice also have seeding competent TDP-43, as determined by a FRET-based biosensor, that persists for weeks upon resolution of TDP-43 aggregate pathology. Human muscle biopsies with TDP-43 pathology also contain TDP-43 aggregate seeds. Using lysates from muscle biopsies of patients with IBM, IMNM and ALS we found that TDP-43 seeding capacity was specific to IBM. Surprisingly, TDP-43 seeding capacity anti-correlated with TDP-43 aggregate and vacuole abundance. These data support that TDP-43 aggregate seeds are present in IBM skeletal muscle and represent a unique TDP-43 pathogenic species not previously appreciated in human muscle disease.}, } @article {pmid38617322, year = {2024}, author = {Lowry, ER and Patel, T and Costa, JA and Chang, E and Tariq, S and Melikyan, H and Davis, IM and Aziz, S and Dermentzaki, G and Lotti, F and Wichterle, H}, title = {Embryonic motor neuron programming factors reactivate immature gene expression and suppress ALS pathologies in postnatal motor neurons.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {38617322}, issn = {2692-8205}, support = {R01 NS109217/NS/NINDS NIH HHS/United States ; K99 NS121136/NS/NINDS NIH HHS/United States ; R21 NS101575/NS/NINDS NIH HHS/United States ; R01 NS116141/NS/NINDS NIH HHS/United States ; R01 AG084965/AG/NIA NIH HHS/United States ; }, abstract = {Aging is a major risk factor in amyotrophic lateral sclerosis (ALS) and other adult-onset neurodegenerative disorders. Whereas young neurons are capable of buffering disease-causing stresses, mature neurons lose this ability and degenerate over time. We hypothesized that the resilience of young motor neurons could be restored by re-expression of the embryonic motor neuron selector transcription factors ISL1 and LHX3. We found that viral re-expression of ISL1 and LHX3 reactivates aspects of the youthful gene expression program in mature motor neurons and alleviates key disease-relevant phenotypes in the SOD1[G93A] mouse model of ALS. Our results suggest that redeployment of lineage-specific neuronal selector transcription factors can be an effective strategy to attenuate age-dependent phenotypes in neurodegenerative disease.}, } @article {pmid38617277, year = {2024}, author = {Liu, D and Webber, HC and Bian, F and Xu, Y and Prakash, M and Feng, X and Yang, M and Yang, H and You, IJ and Li, L and Liu, L and Liu, P and Huang, H and Chang, CY and Liu, L and Shah, SH and Torre, A and Welsbie, DS and Sun, Y and Duan, X and Goldberg, JL and Braun, M and Lansky, Z and Hu, Y}, title = {Optineurin-facilitated axonal mitochondria delivery promotes neuroprotection and axon regeneration.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {38617277}, issn = {2692-8205}, support = {R01 EY034353/EY/NEI NIH HHS/United States ; P30 EY026877/EY/NEI NIH HHS/United States ; R01 EY024932/EY/NEI NIH HHS/United States ; S10 OD025091/OD/NIH HHS/United States ; R01 EY032518/EY/NEI NIH HHS/United States ; R01 EY023295/EY/NEI NIH HHS/United States ; F32 EY029567/EY/NEI NIH HHS/United States ; R01 EY032159/EY/NEI NIH HHS/United States ; R01 EY025295/EY/NEI NIH HHS/United States ; S10 OD030452/OD/NIH HHS/United States ; }, abstract = {Optineurin (OPTN) mutations are linked to amyotrophic lateral sclerosis (ALS) and normal tension glaucoma (NTG), but a relevant animal model is lacking, and the molecular mechanisms underlying neurodegeneration are unknown. We found that OPTN C-terminus truncation (OPTN∆C) causes late-onset neurodegeneration of retinal ganglion cells (RGCs), optic nerve (ON), and spinal cord motor neurons, preceded by a striking decrease of axonal mitochondria. Surprisingly, we discover that OPTN directly interacts with both microtubules and the mitochondrial transport complex TRAK1/KIF5B, stabilizing them for proper anterograde axonal mitochondrial transport, in a C-terminus dependent manner. Encouragingly, overexpressing OPTN/TRAK1/KIF5B reverses not only OPTN truncation-induced, but also ocular hypertension-induced neurodegeneration, and promotes striking ON regeneration. Therefore, in addition to generating new animal models for NTG and ALS, our results establish OPTN as a novel facilitator of the microtubule-dependent mitochondrial transport necessary for adequate axonal mitochondria delivery, and its loss as the likely molecular mechanism of neurodegeneration.}, } @article {pmid38615685, year = {2024}, author = {Beckers, J and Van Damme, P}, title = {Toxic gain-of-function mechanisms in C9orf72 ALS-FTD neurons drive autophagy and lysosome dysfunction.}, journal = {Autophagy}, volume = {20}, number = {9}, pages = {2102-2104}, pmid = {38615685}, issn = {1554-8635}, mesh = {*C9orf72 Protein/genetics/metabolism ; *Autophagy/genetics/physiology ; *Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology ; *Lysosomes/metabolism ; Humans ; *Frontotemporal Dementia/genetics/metabolism/pathology ; *Induced Pluripotent Stem Cells/metabolism ; *Motor Neurons/metabolism/pathology ; Gain of Function Mutation/genetics ; DNA-Binding Proteins/metabolism/genetics ; Neurons/metabolism ; Sequestosome-1 Protein/metabolism/genetics ; }, abstract = {Hexanucleotide repeat expansions in the C9orf72 gene are the primary genetic cause for both amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), two related neurodegenerative diseases. Significant advances in the elucidation of the disease mechanisms responsible for C9orf72 ALS-FTD have revealed both a toxic gain-of-function and a loss-of-function mechanism as possible underlying disease cause. As the differential contribution of both gain and loss of function in C9orf72 ALS-FTD pathogenesis remains debated, we investigated disease mechanisms in motor neurons derived from both authentic human patient C9orf72 ALS-FTD iPSCs as well as a C9orf72 knockout iPSC line. We found that patient neurons presented with less motile and enlarged lysosomes, a decrease in autophagic flux and an increase in SQSTM1/p62 puncta and insoluble TARDBP/TDP-43 species. Importantly, we found that C9orf72 knockout barely has any influence on these phenotypes and mainly results in impaired endosomal maturation. Together, our data suggest that toxic gain-of-function, rather than loss-of-function, mechanisms in C9orf72 ALS-FTD impair the autophagy-lysosome system in neurons.}, } @article {pmid38615537, year = {2024}, author = {Xu, Z and Zhang, J and Tang, J and Gong, Y and Zou, Y and Zhang, Q}, title = {Dissecting the effect of ALS mutation S375G on the conformational properties and aggregation dynamics of TDP-43370-375 fragment.}, journal = {Biophysical chemistry}, volume = {310}, number = {}, pages = {107230}, doi = {10.1016/j.bpc.2024.107230}, pmid = {38615537}, issn = {1873-4200}, mesh = {*Molecular Dynamics Simulation ; Humans ; *Amyotrophic Lateral Sclerosis/genetics/metabolism ; *DNA-Binding Proteins/chemistry/genetics/metabolism ; *Mutation ; Protein Conformation ; Protein Aggregates ; Peptide Fragments/chemistry/genetics/metabolism ; }, abstract = {The aggregation of transactive response deoxyribonucleic acid (DNA) binding protein of 43 kDa (TDP-43) into ubiquitin-positive inclusions is closely associated with amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration, and chronic traumatic encephalopathy. The 370-375 fragment of TDP-43 ([370]GNNSYS[375], TDP-43370-375), the amyloidogenic hexapeptides, can be prone to forming pathogenic amyloid fibrils with the characteristic of steric zippers. Previous experiments reported the ALS-associated mutation, serine 375 substituted by glycine (S375G) is linked to early onset disease and protein aggregation of TDP-43. Based on this, it is necessary to explore the underlying molecular mechanisms. By utilizing all-atom molecular dynamics (MD) simulations of 102 μs in total, we investigated the impact of S375G mutation on the conformational ensembles and oligomerization dynamics of TDP-43370-375 peptides. Our replica exchange MD simulations show that S375G mutation could promote the unstructured conformation formation and induce peptides to form a loose packed oligomer, thus inhibiting the aggregation of TDP-43370-375. Further analyses suggest that S375G mutation displays a reduction effect on the number of total hydrogen bonds and contacts among TDP-43370-375 peptides. Hydrogen bonding and polar interactions among TDP-43370-375 peptides, as well as Y374-Y374 π-π stacking interaction, are attenuated by S375G mutation. Additional microsecond MD simulations demonstrate that S375G mutation could prohibit the conformational conversion to β-structure-rich aggregates and possess an inhibitory effect on the oligomerization dynamics of TDP-43370-375. This study offers for the first time of molecular insights into the S375G mutation affecting the aggregation of TDP-43370-375 at the atomic level, and may open new avenues in the development of future site-specific mutation therapeutics.}, } @article {pmid38614367, year = {2024}, author = {Roghani, AK and Garcia, RI and Roghani, A and Reddy, A and Khemka, S and Reddy, RP and Pattoor, V and Jacob, M and Reddy, PH and Sehar, U}, title = {Treating Alzheimer's disease using nanoparticle-mediated drug delivery strategies/systems.}, journal = {Ageing research reviews}, volume = {97}, number = {}, pages = {102291}, doi = {10.1016/j.arr.2024.102291}, pmid = {38614367}, issn = {1872-9649}, support = {R01 AG069333/AG/NIA NIH HHS/United States ; RF1 AG079264/AG/NIA NIH HHS/United States ; }, mesh = {Humans ; *Alzheimer Disease/drug therapy ; *Drug Delivery Systems/methods ; Animals ; *Blood-Brain Barrier/drug effects/metabolism ; *Nanoparticles/administration & dosage ; Nanoparticle Drug Delivery System ; }, abstract = {The administration of promising medications for the treatment of neurodegenerative disorders (NDDs), such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS) is significantly hampered by the blood-brain barrier (BBB). Nanotechnology has recently come to light as a viable strategy for overcoming this obstacle and improving drug delivery to the brain. With a focus on current developments and prospects, this review article examines the use of nanoparticles to overcome the BBB constraints to improve drug therapy for AD The potential for several nanoparticle-based approaches, such as those utilizing lipid-based, polymeric, and inorganic nanoparticles, to enhance drug transport across the BBB are highlighted. To shed insight on their involvement in aiding effective drug transport to the brain, methods of nanoparticle-mediated drug delivery, such as surface modifications, functionalization, and particular targeting ligands, are also investigated. The article also discusses the most recent findings on innovative medication formulations encapsulated within nanoparticles and the therapeutic effects they have shown in both preclinical and clinical testing. This sector has difficulties and restrictions, such as the need for increased safety, scalability, and translation to clinical applications. However, the major emphasis of this review aims to provide insight and contribute to the knowledge of how nanotechnology can potentially revolutionize the worldwide treatment of NDDs, particularly AD, to enhance clinical outcomes.}, } @article {pmid38613988, year = {2024}, author = {Ruotolo, G and D'Anzi, A and Casamassa, A and Mazzoni, M and Ferrari, D and Lombardi, I and Carletti, RM and D'Asdia, C and Torrente, I and Frezza, K and Lattante, S and Sabatelli, M and Pennuto, M and Vescovi, AL and Rosati, J}, title = {Generation of induced pluripotent stem cells (CSSi017-A)(12862) from an ALS patient carrying a repeat expansion in the C9orf72 gene.}, journal = {Stem cell research}, volume = {77}, number = {}, pages = {103412}, doi = {10.1016/j.scr.2024.103412}, pmid = {38613988}, issn = {1876-7753}, mesh = {Humans ; *Induced Pluripotent Stem Cells/metabolism ; *C9orf72 Protein/genetics/metabolism ; *Amyotrophic Lateral Sclerosis/genetics/pathology ; *DNA Repeat Expansion ; Cell Differentiation ; Fibroblasts/metabolism ; Cell Line ; Male ; }, abstract = {Genetic expansions of the hexanucleotide repeats (GGGGCC) in the C9orf72 gene appear in approximately 40% of patients with familial ALS and 7% of patients with sporadic ALS in the European population, making this mutation one of the most prevalent genetic mutations in ALS. Here, we generated a human induced pluripotent stem cell (hiPSC) line from the dermal fibroblasts of a patient carrying a 56-repeat expansion in an ALS disease-causing allele of C9orf72. These iPSCs showed stable amplification in vitro with normal karyotype and high expression of pluripotent markers and differentiated spontaneously in vivo into three germ layers.}, } @article {pmid38613779, year = {2024}, author = {Huang, Z and Zhou, Y and Liu, Y and Wang, J}, title = {Protocol to identify DNA-binding proteins recognizing nucleotide repeat dsDNAs.}, journal = {STAR protocols}, volume = {5}, number = {2}, pages = {103013}, pmid = {38613779}, issn = {2666-1667}, support = {R01 NS089616/NS/NINDS NIH HHS/United States ; R01 NS128494/NS/NINDS NIH HHS/United States ; }, mesh = {*DNA/metabolism/genetics ; Humans ; *DNA-Binding Proteins/metabolism/genetics ; Electrophoretic Mobility Shift Assay/methods ; C9orf72 Protein/genetics/metabolism ; Isotope Labeling/methods ; }, abstract = {DNA-binding proteins perform diverse functions, including regulating cellular growth and orchestrating chromatin architecture. Here, we present a protocol to discover proteins specifically interacting with a hexanucleotide repeat DNA, the expansion of which is known as the most frequent genetic cause of familial C9orf72 amyotrophic lateral sclerosis and frontotemporal dementia. We describe steps to fish out DNA-binding proteins recognizing double-stranded repeat DNAs using a SILAC (stable isotope labelling by amino acids in cell culture)-based approach and validate the results using electrophoretic mobility shift assay. For complete details on the use and execution of this protocol, please refer to Liu et al.[1].}, } @article {pmid38613054, year = {2024}, author = {López-Gómez, JJ and Izaola-Jauregui, O and Almansa-Ruiz, L and Jiménez-Sahagún, R and Primo-Martín, D and Pedraza-Hueso, MI and Ramos-Bachiller, B and González-Gutiérrez, J and De Luis-Román, D}, title = {Use of Muscle Ultrasonography in Morphofunctional Assessment of Amyotrophic Lateral Sclerosis (ALS).}, journal = {Nutrients}, volume = {16}, number = {7}, pages = {}, pmid = {38613054}, issn = {2072-6643}, mesh = {Female ; Humans ; Male ; Middle Aged ; *Amyotrophic Lateral Sclerosis/diagnostic imaging ; Body Mass Index ; *Deglutition Disorders ; *Malnutrition ; Quadriceps Muscle/diagnostic imaging ; Prospective Studies ; }, abstract = {UNLABELLED: Amyotrophic lateral sclerosis (ALS) is a progressive disease with a high prevalence of malnutrition that can influence prognosis. The main objective of this study is to compare the validity of muscle ultrasonography in the diagnosis of malnutrition and the prognosis of patients with ALS.

METHODS: This is a prospective observational study that analyzes the nutritional status of patients at the beginning of nutritional monitoring. The morphofunctional assessment included the examination of anthropometric variables such as weight, height, body mass index (BMI), arm circumference, and calf circumference. Additionally, electrical bioimpedanciometry (BIA) was used to measure electrical parameters and estimate other relevant metrics. Muscle ultrasonography[®] (quadriceps rectus femoris (QRF)) assessed muscle mass parameters, including muscle area index (MARAI), anteroposterior diameter of the QRF (Y-axis) (cm), transverse diameter of the QRF (X-axis) (cm), and the sum of the quadriceps thickness (RF+VI) (cm), as well as muscle quality parameters such as echogenicity and the Y-X index.

RESULTS: A total of 37 patients diagnosed with amyotrophic lateral sclerosis (ALS) were included in this study. Of these patients, 51.4% were men. The mean age was 64.27 (12.59) years. A total of 54.1% of the patients had a bulbar onset of amyotrophic lateral sclerosis, and 45.9% had spinal onset. The percentage of subjects with malnutrition diagnosed by the Global Leadership Initiative on Malnutrition (GLIM) criteria was 45.9% of patients. There was a direct correlation between muscle mass parameters assessed by muscle ultrasonography (RF+VI) and active mass markers measured by bioimpedanciometry (body cellular mass index (BCMI) (r = 0.62; p < 0.01), fat-free mass index (FFMI) (r = 0.75; p < 0.01), and appendicular skeletal mass index (ASMI) (r = 0.69; p < 0.01)). There was a direct correlation between echogenicity and resistance (r = 0.44; p = 0.02), as well as between the fat-free mass index and the Y-X index (r = 0.36; p = 0.14). Additionally, there was a negative correlation between echogenicity and BCMI (r = -0.46; p < 0.01) and ASMI (r = 0.34; p = 0.06). Patients with low quadriceps thickness (male < 2.49 cm; female < 1.84 cm) showed an increased risk of hospital admission adjusted by age, sex, and presence of dysphagia (OR: 7.84 (CI 95%: 1.09-56.07); p-value = 0.04), and patients with low-quality mass (Y-X index < 0.35) had a higher risk of hospital admission adjusted by age, sex, and presence of dysphagia (OR: 19.83 (CI 95%: 1.77-222.46); p-value = 0.02).

CONCLUSIONS: In patients with ALS, ultrasonography echogenicity was inversely related to BCMI, FFMI, and ASMI, and the Y-X index was directly related to FFMI. The lowest quartiles of quadriceps thickness and Y-X index are risk factors for hospital admission.}, } @article {pmid38612804, year = {2024}, author = {Giri, PM and Banerjee, A and Ghosal, A and Layek, B}, title = {Neuroinflammation in Neurodegenerative Disorders: Current Knowledge and Therapeutic Implications.}, journal = {International journal of molecular sciences}, volume = {25}, number = {7}, pages = {}, pmid = {38612804}, issn = {1422-0067}, support = {P20 GM109024/GM/NIGMS NIH HHS/United States ; 2P20M109024/GM/NIGMS NIH HHS/United States ; }, mesh = {Humans ; Neuroinflammatory Diseases ; Inflammation/therapy ; *Alzheimer Disease ; *Amyotrophic Lateral Sclerosis ; Central Nervous System ; }, abstract = {Neurodegenerative disorders (NDs) have become increasingly common during the past three decades. Approximately 15% of the total population of the world is affected by some form of NDs, resulting in physical and cognitive disability. The most common NDs include Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease. Although NDs are caused by a complex interaction of genetic, environmental, and lifestyle variables, neuroinflammation is known to be associated with all NDs, often leading to permanent damage to neurons of the central nervous system. Furthermore, numerous emerging pieces of evidence have demonstrated that inflammation not only supports the progression of NDs but can also serve as an initiator. Hence, various medicines capable of preventing or reducing neuroinflammation have been investigated as ND treatments. While anti-inflammatory medicine has shown promising benefits in several preclinical models, clinical outcomes are often questionable. In this review, we discuss various NDs with their current treatment strategies, the role of neuroinflammation in the pathophysiology of NDs, and the use of anti-inflammatory agents as a potential therapeutic option.}, } @article {pmid38612745, year = {2024}, author = {Ke, H and Chen, Y and Zhang, B and Duan, S and Ma, X and Ren, B and Wang, Y}, title = {Odorant Receptors Expressing and Antennal Lobes Architecture Are Linked to Caste Dimorphism in Asian Honeybee, Apis cerana (Hymenoptera: Apidae).}, journal = {International journal of molecular sciences}, volume = {25}, number = {7}, pages = {}, pmid = {38612745}, issn = {1422-0067}, support = {2023YFE0113600//National Key Research and Development Program "Intergovernmental international cooperation on science, technology and innovation"/ ; 20200402001NC//Natural Science Foundation of Jilin Province/ ; 20190301047NY//Natural Science Foundation of Jilin Province/ ; }, mesh = {Bees/genetics ; Animals ; *Hymenoptera ; Sex Characteristics ; Cell Communication ; Food ; *Receptors, Odorant/genetics ; }, abstract = {Insects heavily rely on the olfactory system for food, mating, and predator evasion. However, the caste-related olfactory differences in Apis cerana, a eusocial insect, remain unclear. To explore the peripheral and primary center of the olfactory system link to the caste dimorphism in A. cerana, transcriptome and immunohistochemistry studies on the odorant receptors (ORs) and architecture of antennal lobes (ALs) were performed on different castes. Through transcriptomesis, we found more olfactory receptor genes in queens and workers than in drones, which were further validated by RT-qPCR, indicating caste dimorphism. Meanwhile, ALs structure, including volume, surface area, and the number of glomeruli, demonstrated a close association with caste dimorphism. Particularly, drones had more macroglomeruli possibly for pheromone recognition. Interestingly, we found that the number of ORs and glomeruli ratio was nearly 1:1. Also, the ORs expression distribution pattern was very similar to the distribution of glomeruli volume. Our results suggest the existence of concurrent plasticity in both the peripheral olfactory system and ALs among different castes of A. cerana, highlighting the role of the olfactory system in labor division in insects.}, } @article {pmid38612591, year = {2024}, author = {Moțățăianu, A and Andone, S and Stoian, A and Bălașa, R and Huțanu, A and Sărmășan, E}, title = {A Potential Role of Interleukin-5 in the Pathogenesis and Progression of Amyotrophic Lateral Sclerosis: A New Molecular Perspective.}, journal = {International journal of molecular sciences}, volume = {25}, number = {7}, pages = {}, pmid = {38612591}, issn = {1422-0067}, support = {293/5/2020//University of Medicine and Pharmacy of Târgu Mureş/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis ; Cytokines ; Disease Progression ; *Interleukin-5 ; Upper Extremity ; }, abstract = {Cumulative data suggest that neuroinflammation plays a prominent role in amyotrophic lateral sclerosis (ALS) pathogenesis. The purpose of this work was to assess if patients with ALS present a specific peripheral cytokine profile and if it correlates with neurological disability assessed by ALSFRS-R, the rate of disease progression, and the pattern of disease progression (horizontal spreading [HSP] versus vertical spreading [VSP]). We determined the levels of 15 cytokines in the blood of 59 patients with ALS and 40 controls. We identified a positive correlation between levels of pro-inflammatory cytokines (interleukin [IL]-17F, IL-33, IL-31) and the age of ALS patients, as well as a positive correlation between IL-12p/70 and survival from ALS onset and ALS diagnosis. Additionally, there was a positive correlation between the ALSFRS-R score in the upper limb and respiratory domain and IL-5 levels. In our ALS cohort, the spreading pattern was 42% horizontal and 58% vertical, with patients with VSP showing a faster rate of ALS progression. Furthermore, we identified a negative correlation between IL-5 levels and the rate of disease progression, as well as a positive correlation between IL-5 and HSP of ALS. To the best of our knowledge, this is the first study reporting a "protective" role of IL-5 in ALS.}, } @article {pmid38612448, year = {2024}, author = {Homma, H and Tanaka, H and Fujita, K and Okazawa, H}, title = {Necrosis Links Neurodegeneration and Neuroinflammation in Neurodegenerative Disease.}, journal = {International journal of molecular sciences}, volume = {25}, number = {7}, pages = {}, pmid = {38612448}, issn = {1422-0067}, mesh = {Humans ; *HMGB1 Protein ; *Neurodegenerative Diseases ; Neuroinflammatory Diseases ; Necrosis ; Cell Death ; }, abstract = {The mechanisms of neuronal cell death in neurodegenerative disease remain incompletely understood, although recent studies have made significant advances. Apoptosis was previously considered to be the only mechanism of neuronal cell death in neurodegenerative diseases. However, recent findings have challenged this dogma, identifying new subtypes of necrotic neuronal cell death. The present review provides an updated summary of necrosis subtypes and discusses their potential roles in neurodegenerative cell death. Among numerous necrosis subtypes, including necroptosis, paraptosis, ferroptosis, and pyroptosis, transcriptional repression-induced atypical cell death (TRIAD) has been identified as a potential mechanism of neuronal cell death. TRIAD is induced by functional deficiency of TEAD-YAP and self-amplifies via the release of HMGB1. TRIAD is a feasible potential mechanism of neuronal cell death in Alzheimer's disease and other neurodegenerative diseases. In addition to induction of cell death, HMGB1 released during TRIAD activates brain inflammatory responses, which is a potential link between neurodegeneration and neuroinflammation.}, } @article {pmid38610601, year = {2024}, author = {Piñar-Gutiérrez, A and González-Gracia, L and Vázquez Gutiérrez, R and García-Rey, S and Jiménez-Sánchez, A and González-Navarro, I and Tatay-Domínguez, D and Garrancho-Domínguez, P and Remón-Ruiz, PJ and Martínez-Ortega, AJ and Serrano-Aguayo, P and Giménez-Andreu, MD and García-Fernández, FJ and Bozada-García, JM and Nacarino-Mejías, V and López-Iglesias, Á and Pereira-Cunill, JL and García-Luna, PP}, title = {Percutaneous Gastrostomies: Associated Complications in PUSH vs. PULL Techniques over 12 Years in a Referral Centre.}, journal = {Journal of clinical medicine}, volume = {13}, number = {7}, pages = {}, pmid = {38610601}, issn = {2077-0383}, abstract = {Objectives: To compare complications associated with percutaneous gastrostomies performed using PUSH and PULL techniques, whether endoscopic (PEG) or radiological (PRG), in a tertiary-level hospital. Methods: This was a prospective observational study. Adult patients who underwent percutaneous PULL or PUSH gastrostomy using PEG or PRG techniques at the Virgen del Rocio University Hospital and subsequently followed up in the Nutrition Unit between 2009-2020 were included. X2 tests or Fisher's test were used for the comparison of proportions when necessary. Univariate analysis was conducted to study risk factors for PRG-associated complications. Results: n = 423 (PULL = 181; PUSH = 242). The PULL technique was associated with a higher percentage of total complications (37.6% vs. 23.8%; p = 0.005), exudate (18.2% vs. 11.2%; p = 0.039), and irritation (3.3% vs. 0%; p = 0.006). In the total sample, there were 5 (1.1%) cases of peritonitis, 3 (0.7%) gastrocolic fistulas, and 1 (0.2%) death due to complications associated with gastrostomy. Gender, age, and different indications were not risk factors for a higher number of complications. The most common indications were neurological diseases (35.9%), head and neck cancer (29%), and amyotrophic lateral sclerosis (17.2%). Conclusions: The PULL technique was associated with more total complications than the PUSH technique, but both were shown to be safe techniques, as the majority of complications were minor.}, } @article {pmid38610566, year = {2024}, author = {Maset-Roig, R and Caplliure-Llopis, J and de Bernardo, N and Privado, J and Alarcón-Jiménez, J and Martín-Ruiz, J and Botella-Navas, M and Villarón-Casales, C and Sancho-Cantus, D and de la Rubia Ortí, JE}, title = {Analysis of Heart Rate Variability in Individuals Affected by Amyotrophic Lateral Sclerosis.}, journal = {Sensors (Basel, Switzerland)}, volume = {24}, number = {7}, pages = {}, pmid = {38610566}, issn = {1424-8220}, support = {2017-216-001//Catholic University of Valencia/ ; }, mesh = {Male ; Humans ; Female ; *Amyotrophic Lateral Sclerosis ; Heart Rate ; Autonomic Nervous System ; Health Status ; Heart ; }, abstract = {INTRODUCTION: Amyotrophic lateral sclerosis (ALS) produces alterations in the autonomic nervous system (ANS), which explains the cardiac manifestations observed in patients. The assessment of heart rate variability (HRV) is what best reflects the activity of the ANS on heart rate. The Polar H7 Bluetooth[®] device proves to be a non-invasive and much faster technology than existing alternatives for this purpose.

OBJECTIVE: The goal of this study is to determine HRV using Polar H7 Bluetooth technology in ALS patients, comparing the obtained measurements with values from healthy individuals.

METHOD: The sample consisted of 124 participants: 68 diagnosed with ALS and 56 healthy individuals. Using Polar H7 Bluetooth technology and the ELITE HRV application, various HRV measurements were determined for all participants, specifically the HRV index, RMSSD, RMSSD LN, SDNN index, PNN50, LF, HF, LF/HF ratio, HR average, and HF peak frequency.

RESULTS: Statistically significant differences were observed between ALS patients and healthy individuals in the HRV index, RMSSD, RMSSD LN, SDNN index, PNN50, HF, and LF, where healthy individuals exhibited higher scores. For the HR average, the ALS group showed a higher value. Values were similar when comparing men and women with ALS, with only a higher HF peak frequency observed in women.

CONCLUSION: The Polar H7 Bluetooth[®] device is effective in determining heart rate variability alterations in ALS, being a promising prognostic tool for the disease.}, } @article {pmid38610192, year = {2024}, author = {Papadopoulou, M and Papapostolou, A and Dimakopoulos, R and Salakou, S and Koropouli, E and Fanouraki, S and Bakola, E and Moschovos, C and Tsivgoulis, G}, title = {Non-Pharmacological Interventions on Pain in Amyotrophic Lateral Sclerosis Patients: A Systematic Review and Meta-Analysis.}, journal = {Healthcare (Basel, Switzerland)}, volume = {12}, number = {7}, pages = {}, pmid = {38610192}, issn = {2227-9032}, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder affecting upper and lower motor neurons. Some ALS patients exhibit concomitant nonmotor signs; thus, ALS is considered a multisystemic disorder. Pain is an important nonmotor symptom. Observational and case-control studies report high frequency of pain in ALS patients and it has been correlated with depression and quality of life. There are no specific scales for the assessment of pain and no randomized controlled trials (RCTs) regarding the drug management of pain in ALS.

AIM: To systematically review the evidence for the nonpharmacological interventions (NPIs) in relieving pain in ALS, on March 2024, we searched the following databases: Pubmed, Scopus, Web of Science, and Cochrane. We also checked the bibliographies of trials identified to include further published or unpublished trials.

MAIN RESULTS: A total of 1003 records were identified. Finally, five RCTs including 131 patients (64 in the intervention group and 67 in the control group) were included for meta-analysis. The interventions of the included RCTs consisted of muscle exercise, combined aerobics-strength intervention, and osteopathic manual treatment. The meta-analysis did not find a statistically significant difference in favor of NPIs for alleviating pain in ALS patients.

CONCLUSIONS: ALS has a fulminant course and irreversibly leads to death. Pain in ALS patients, although a common nonmotor symptom, is often unrecognized and undertreated, and this is underlined by the lack of any RCTs on drug therapy for pain. Albeit NPIs are considered safe, as adverse effects are rarely reported, this systematic review did not provide sufficient evidence for a beneficial effect on pain. The scarceness of relevant literature highlights the need for future studies, with larger samples, more homogeneous in terms of interventions and population characteristics (stage of disease), and better choice of measurement scales to further investigate the efficacy, if any, of various pain interventions in ALS patients.}, } @article {pmid38610119, year = {2024}, author = {Vandenbogaerde, I and Van den Block, L and Deliens, L and Carduff, E and van der Heide, A and De Bleecker, J and De Vleminck, A}, title = {Experiences with advance care planning in amyotrophic lateral sclerosis: Qualitative longitudinal study with people with amyotrophic lateral sclerosis and their family carers.}, journal = {Palliative medicine}, volume = {38}, number = {5}, pages = {572-581}, doi = {10.1177/02692163241242320}, pmid = {38610119}, issn = {1477-030X}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/psychology/therapy ; *Advance Care Planning ; Male ; Female ; *Caregivers/psychology ; Middle Aged ; Longitudinal Studies ; Aged ; *Qualitative Research ; Adult ; Aged, 80 and over ; Terminal Care/psychology ; }, abstract = {BACKGROUND: It is unclear when people with amyotrophic lateral sclerosis and their family carers think about their future, what they would prefer in terms of care, and how their ideas change over time.

AIM: Understanding experiences with advance care planning of persons with amyotrophic lateral sclerosis and their family carers-and if, when, how, and why these experiences change over time.

DESIGN: A qualitative longitudinal interview study. Analysis involved content analysis, followed by a two-step timeline method to describe changes in advance care planning experiences within and across participants.

SETTING/PARTICIPANTS: Nine persons with amyotrophic lateral sclerosis and nine family carers who were interviewed three times over a 9-month period.

RESULTS: All participants thought about future care, but few talked about it. Over time, advance care planning experiences were influenced by intertwined elements: (1) experienced physical decline and related future care needs; (2) how persons with amyotrophic lateral sclerosis identify themselves as patients; (3) obtaining information about diagnosis and prognosis; (4) professionals initiating conversations about medical aspects of end-of-life decisions; (5) balancing between hope to remain stable and worry about the future; and (6) protecting themselves and each other from worries about the future.

CONCLUSION: This study emphasizes how factors such as coping with the disease and relational dynamics shape individuals' thoughts about future care over time and how psychological, social, and medical factors are interwoven in advance care planning. The findings advocate for a process-oriented perspective, portraying advance care planning as an ongoing dialog, encompassing the needs, concerns, and emotions of both people with amyotrophic lateral sclerosis and their family carers.}, } @article {pmid38610012, year = {2024}, author = {Liu, X and Shen, L and Wan, M and Xie, H and Wang, Z}, title = {Peripheral extracellular vesicles in neurodegeneration: pathogenic influencers and therapeutic vehicles.}, journal = {Journal of nanobiotechnology}, volume = {22}, number = {1}, pages = {170}, pmid = {38610012}, issn = {1477-3155}, support = {82301625; 81801395; 82125023; 82072504; 81871822; U22A20300, 81971029//National Natural Science Foundation of China/ ; 82301625; 81801395; 82125023; 82072504; 81871822; U22A20300, 81971029//National Natural Science Foundation of China/ ; 82301625; 81801395; 82125023; 82072504; 81871822; U22A20300, 81971029//National Natural Science Foundation of China/ ; 82301625; 81801395; 82125023; 82072504; 81871822; U22A20300, 81971029//National Natural Science Foundation of China/ ; 2020YFC2008500//National Key R&D Program of China/ ; }, mesh = {Humans ; Prospective Studies ; *Extracellular Vesicles ; *Exosomes ; *Parkinson Disease ; *Alzheimer Disease ; }, abstract = {Neurodegenerative diseases (NDDs) such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis epitomize a class of insidious and relentless neurological conditions that are difficult to cure. Conventional therapeutic regimens often fail due to the late onset of symptoms, which occurs well after irreversible neurodegeneration has begun. The integrity of the blood-brain barrier (BBB) further impedes efficacious drug delivery to the central nervous system, presenting a formidable challenge in the pharmacological treatment of NDDs. Recent scientific inquiries have shifted focus toward the peripheral biological systems, investigating their influence on central neuropathology through the lens of extracellular vesicles (EVs). These vesicles, distinguished by their ability to breach the BBB, are emerging as dual operatives in the context of NDDs, both as conveyors of pathogenic entities and as prospective vectors for therapeutic agents. This review critically summarizes the burgeoning evidence on the role of extracerebral EVs, particularly those originating from bone, adipose tissue, and gut microbiota, in modulating brain pathophysiology. It underscores the duplicity potential of peripheral EVs as modulators of disease progression and suggests their potential as novel vehicles for targeted therapeutic delivery, positing a transformative impact on the future landscape of NDD treatment strategies. Search strategy A comprehensive literature search was conducted using PubMed, Web of Science, and Scopus from January 2000 to December 2023. The search combined the following terms using Boolean operators: "neurodegenerative disease" OR "Alzheimer's disease" OR "Parkinson's disease" OR "Amyotrophic lateral sclerosis" AND "extracellular vesicles" OR "exosomes" OR "outer membrane vesicles" AND "drug delivery systems" AND "blood-brain barrier". MeSH terms were employed when searching PubMed to refine the results. Studies were included if they were published in English, involved human subjects, and focused on the peripheral origins of EVs, specifically from bone, adipose tissue, and gut microbiota, and their association with related diseases such as osteoporosis, metabolic syndrome, and gut dysbiosis. Articles were excluded if they did not address the role of EVs in the context of NDDs or did not discuss therapeutic applications. The titles and abstracts of retrieved articles were screened using a dual-review process to ensure relevance and accuracy. The reference lists of selected articles were also examined to identify additional relevant studies.}, } @article {pmid38609957, year = {2024}, author = {Charrin, L and Romain-Scelle, N and Di-Filippo, C and Mercier, E and Balen, F and Tazarourte, K and Benhamed, A}, title = {Impact of delayed mobile medical team dispatch for respiratory distress calls: a propensity score matched study from a French emergency communication center.}, journal = {Scandinavian journal of trauma, resuscitation and emergency medicine}, volume = {32}, number = {1}, pages = {27}, pmid = {38609957}, issn = {1757-7241}, mesh = {Adult ; Humans ; Male ; Aged ; Cross-Sectional Studies ; Propensity Score ; *Communication ; *Catecholamines ; Dyspnea ; }, abstract = {BACKGROUND: Shortness of breath is a common complaint among individuals contacting emergency communication center (EMCCs). In some prehospital system, emergency medical services include an advanced life support (ALS)-capable team. Whether such team should be dispatched during the phone call or delayed until the BLS-capable paramedic team reports from the scene is unclear. We aimed to evaluate the impact of delayed MMT dispatch until receiving the paramedic review compared to immediate dispatch at the time of the call on patient outcomes.

METHODS: A cross-sectional study conducted in Lyon, France, using data obtained from the departmental EMCC during the period from January to December 2019. We included consecutive calls related to adult patients experiencing acute respiratory distress. Patients from the two groups (immediate mobile medical team (MMT) dispatch or delayed MMT dispatch) were matched on a propensity score, and a conditional weighted logistic regression assessed the adjusted odds ratios (ORs) for each outcome (mortality on days 0, 7 and 30).

RESULTS: A total of 870 calls (median age 72 [57-84], male 466 53.6%) were sought for analysis [614 (70.6%) "immediate MMT dispatch" and 256 (29.4%) "delayed MMT" groups]. The median time before MMT dispatch was 25.1 min longer in the delayed MMT group (30.7 [26.4-36.1] vs. 5.6 [3.9-8.8] min, p < 0.001). Patients subjected to a delayed MMT intervention were older (median age 78 [66-87] vs. 69 [53-83], p < 0.001) and more frequently highly dependent (16.3% vs. 8.6%, p < 0.001). A higher proportion of patients in the delayed MMT group required bag valve mask ventilation (47.3% vs. 39.1%, p = 0.03), noninvasive ventilation (24.6% vs. 20.0%, p = 0.13), endotracheal intubation (7.0% vs. 4.1%, p = 0.07) and catecholamine infusion (3.9% vs. 1.3%, p = 0.01). After propensity score matching, mortality at day 0 was higher in the delayed MMT group (9.8% vs. 4.2%, p = 0.002). Immediate MMT dispatch at the call was associated with a lower risk of mortality on day 0 (0.60 [0.38;0.82], p < 0.001) day 7 (0.50 [0.27;0.72], p < 0.001) and day 30 (0.56 [0.35;0.78], p < 0.001) CONCLUSIONS: This study suggests that the deployment of an MMT at call in patients in acute respiratory distress may result in decreased short to medium-term mortality compared to a delayed MMT following initial first aid assessment.}, } @article {pmid38609750, year = {2024}, author = {Sellier, C and Corcia, P and Vourc'h, P and Dupuis, L}, title = {C9ORF72 hexanucleotide repeat expansion: From ALS and FTD to a broader pathogenic role?.}, journal = {Revue neurologique}, volume = {180}, number = {5}, pages = {417-428}, doi = {10.1016/j.neurol.2024.03.008}, pmid = {38609750}, issn = {0035-3787}, mesh = {Humans ; *C9orf72 Protein/genetics ; *Amyotrophic Lateral Sclerosis/genetics ; *Frontotemporal Dementia/genetics ; *DNA Repeat Expansion ; Phenotype ; Genetic Association Studies/methods ; Proteins/genetics ; }, abstract = {The major gene underlying monogenic forms of amyotrophic lateral sclerosis (ALS) and fronto-temporal dementia (FTD) is C9ORF72. The causative mutation in C9ORF72 is an abnormal hexanucleotide (G4C2) repeat expansion (HRE) located in the first intron of the gene. The aim of this review is to propose a comprehensive update on recent developments on clinical, biological and therapeutics aspects related to C9ORF72 in order to highlight the current understanding of genotype-phenotype correlations, and also on biological machinery leading to neuronal death. We will particularly focus on the broad phenotypic presentation of C9ORF72-related diseases, that goes well beyond the classical phenotypes observed in ALS and FTD patients. Last, we will comment the possible therapeutical hopes for patients carrying a C9ORF72 HRE.}, } @article {pmid38609711, year = {2024}, author = {Lin, Y and Wang, S and Yang, Q}, title = {Identification of hub genes and diagnostic efficacy for triple-negative breast cancer through WGCNA and Mendelian randomization.}, journal = {Discover oncology}, volume = {15}, number = {1}, pages = {117}, pmid = {38609711}, issn = {2730-6011}, support = {3502Z20227344//Xiamen Science and Technology Plan Project/ ; }, abstract = {OBJECTIVE: Triple-negative breast cancer (TNBC) represents a particularly aggressive form of breast cancer with a poor prognosis due to a lack of targeted treatments resulting from limited a understanding of the underlying mechanisms. The aim of this study was the identification of hub genes for TNBC and assess their clinical applicability in predicting the disease.

METHODS: This study employed a combination of weighted gene co-expression network analysis (WGCNA) and differentially expressed genes (DEGs) to identify new susceptible modules and central genes in TNBC. The potential functional roles of the central genes were investigated using Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses. Furthermore, a predictive model and ROC curve were developed to assess the diagnostic performance of the identified central genes. The correlation between CCNB1 and immune cells proportion was also investigated. At last, a Mendelian randomization (MR) analysis utilizing Genome-Wide Association Study (GWAS) data was analyzed to establish the causal effect of CCNB1 level on TNBC.

RESULTS: WGCNA was applied to determine gene co-expression maps and identify the most relevant module. Through a screening process, 1585 candidate hub genes were subsequently identified with WGCNA and DEGs. GO and KEGG function enrichment analysis indicated that these core genes were related to various biological processes, such as organelle fission, chromosome segregation, nuclear division, mitotic cell cycle phase transition, the cell cycle, amyotrophic lateral sclerosis, and motor proteins. Using STRING and Cytoscape, the top five genes with high degrees were identified as CDC2, CCNB1, CCNA2, TOP2A, and CCNB2. The nomogram model demonstrated good performance in predicting TNBC risk and was proven effective in diagnosis, as evidenced by the receiver operating characteristic (ROC) curve. Further investigation revealed a causal association between CCNB1 and immune cell infiltrates in TNBC. Survival analysis revealed high expression of the CCNB1 gene leads to poorer prognosis in TNBC patients. Additionally, analysis using inverse variance weighting revealed that CCNB1 was linked to a 2.8% higher risk of TNBC (OR: 1.028, 95% CI 1.002-1.055, p = 0.032).

CONCLUSION: We established a co-expression network using the WGCNA methodology to detect pivotal genes associated with TNBC. This finding holds promise for advancing the creation of pre-symptomatic diagnostic tools and deepening our comprehension of the pathogenic mechanisms involved in TNBC risk genes.}, } @article {pmid38609644, year = {2024}, author = {Khalil, M and Teunissen, CE and Lehmann, S and Otto, M and Piehl, F and Ziemssen, T and Bittner, S and Sormani, MP and Gattringer, T and Abu-Rumeileh, S and Thebault, S and Abdelhak, A and Green, A and Benkert, P and Kappos, L and Comabella, M and Tumani, H and Freedman, MS and Petzold, A and Blennow, K and Zetterberg, H and Leppert, D and Kuhle, J}, title = {Neurofilaments as biomarkers in neurological disorders - towards clinical application.}, journal = {Nature reviews. Neurology}, volume = {20}, number = {5}, pages = {269-287}, pmid = {38609644}, issn = {1759-4766}, mesh = {Humans ; *Biomarkers/metabolism/blood ; *Intermediate Filaments/metabolism ; *Nervous System Diseases/diagnosis/metabolism/blood ; *Neurofilament Proteins/blood/metabolism ; }, abstract = {Neurofilament proteins have been validated as specific body fluid biomarkers of neuro-axonal injury. The advent of highly sensitive analytical platforms that enable reliable quantification of neurofilaments in blood samples and simplify longitudinal follow-up has paved the way for the development of neurofilaments as a biomarker in clinical practice. Potential applications include assessment of disease activity, monitoring of treatment responses, and determining prognosis in many acute and chronic neurological disorders as well as their use as an outcome measure in trials of novel therapies. Progress has now moved the measurement of neurofilaments to the doorstep of routine clinical practice for the evaluation of individuals. In this Review, we first outline current knowledge on the structure and function of neurofilaments. We then discuss analytical and statistical approaches and challenges in determining neurofilament levels in different clinical contexts and assess the implications of neurofilament light chain (NfL) levels in normal ageing and the confounding factors that need to be considered when interpreting NfL measures. In addition, we summarize the current value and potential clinical applications of neurofilaments as a biomarker of neuro-axonal damage in a range of neurological disorders, including multiple sclerosis, Alzheimer disease, frontotemporal dementia, amyotrophic lateral sclerosis, stroke and cerebrovascular disease, traumatic brain injury, and Parkinson disease. We also consider the steps needed to complete the translation of neurofilaments from the laboratory to the management of neurological diseases in clinical practice.}, } @article {pmid38608469, year = {2024}, author = {Lee, AF and Chang, YH and Chien, LT and Yang, SC and Chiang, WC}, title = {A comparison between intraosseous and intravenous access in patients with out-of-hospital cardiac arrest: A retrospective cohort study.}, journal = {The American journal of emergency medicine}, volume = {80}, number = {}, pages = {162-167}, doi = {10.1016/j.ajem.2024.04.009}, pmid = {38608469}, issn = {1532-8171}, mesh = {Humans ; *Out-of-Hospital Cardiac Arrest/therapy ; Retrospective Studies ; *Infusions, Intraosseous/methods ; Male ; Female ; Middle Aged ; Aged ; Taiwan ; Cardiopulmonary Resuscitation/methods ; Emergency Medical Services/methods ; Aged, 80 and over ; }, abstract = {INTRODUCTION: The optimal vascular access for patients with out-of-hospital cardiac arrest (OHCA) remains controversial. Increasing evidence supports intraosseous (IO) access due to faster medication administration and higher first-attempt success rates compared to intravenous (IV) access. However, the impact on patient outcomes has been inconclusive.

METHODS: This retrospective cohort study in Taoyuan City, Taiwan, from January 1, 2019, to December 31, 2022, included patients aged ≥18 years with non-traumatic OHCA resuscitated by emergency medical technician paramedics (EMT-Ps) with either IVs or IOs for final vascular access. The exclusion criteria were cardiac arrest en route to the hospital and resuscitation during the coronavirus pandemic (from May 1, 2022, to October 31, 2022). The primary and secondary outcomes were sustained ROSC (≥2 h) and cerebral performance category (CPC) 1-2, respectively. Univariate logistic regression was used to estimate the odds ratios (ORs) and 95% confidence intervals (CI) for the primary analysis. Multivariable logistic regression was employed, with variables selected based on a p-value of <0.05 in the univariate analysis. The survival benefits of different insertion sites and subgroups like general ambulance teams (with a composition that includes fewer EMT-Ps and limited experience in using IO access) were also analyzed.

RESULTS: A total of 2003 patients were enrolled; 1602 received IV access and 401 IO access. The median patient age was 70 years, and most were male (66.6%). Compared to patients receiving IV access, the adjusted odds ratios (aORs) for primary and secondary outcomes in patients with IOs were 0.83 (95% confidence interval [CI], 0.61-1.11; p = 0.20) and 0.96 (95% CI, 0.39-2.40; p = 0.93), respectively. Different insertion sites showed no outcome differences. In the subgroups of females and patients resuscitated by general ambulance teams, the aORs for sustained ROSC were 0.55 (95% CI, 0.33-0.92; p = 0.02) and 0.62 (95% CI, 0.41-0.94; p = 0.02), respectively.

CONCLUSIONS: For patients with OHCA resuscitated by EMT-Ps, IO access was comparable to IV access regarding patient outcomes. However, in females and patients resuscitated by general ambulance teams, IV access might be favorable.}, } @article {pmid38608255, year = {2025}, author = {Igarashi, S and Hioki, S and Sakamaru, N and Suzuki, A and Kurokawa, M and Kato, E}, title = {Flavan-3-ols, flavonoids, anthocyanidins and triterpenoids induces TIE2 phosphorylation -a candidate target for the vascular protective effects.}, journal = {Natural product research}, volume = {39}, number = {12}, pages = {3481-3485}, doi = {10.1080/14786419.2024.2340049}, pmid = {38608255}, issn = {1478-6427}, mesh = {Humans ; *Anthocyanins/pharmacology/chemistry ; Phosphorylation/drug effects ; *Flavonoids/pharmacology/chemistry ; *Receptor, TIE-2/metabolism ; *Triterpenes/pharmacology/chemistry ; HeLa Cells ; Molecular Structure ; Endothelial Cells/drug effects ; }, abstract = {Vascular system is essential for the body to maintain health. Dysregulated vascular system leads to cardiovascular diseases and are observed in ischaemic stroke, Alzheimer's disease, amyotrophic lateral sclerosis, and diabetes. TIE2 is a tyrosine kinase receptor expressed on vascular endothelial cells and contributes to the maintenance of a vascular system. In this paper, we screened for natural products with an activity to induce phosphorylation of TIE2, which will be beneficial for protection of a vascular system. Employing HeLa cells expressing TIE2, flavan-3-ols, flavonoids, anthocyanidins and triterpenoids were identified as active compounds that induce TIE2 phosphorylation. Several of the identified compounds are previously reported to protect endothelial cells from inflammation. Thus, the result provided TIE2 as the candidate receptor protein of those compounds for the protective effect of endothelial cells and the identified compounds will be a good candidate for maintenance of a vascular system.}, } @article {pmid38607533, year = {2024}, author = {Trinchillo, A and Valente, V and Esposito, M and Migliaccio, M and Iovino, A and Picciocchi, M and Cuomo, N and Caccavale, C and Nocerino, C and De Rosa, L and Salvatore, E and Pierantoni, GM and Menchise, V and Paladino, S and Criscuolo, C}, title = {Expanding SPG18 clinical spectrum: autosomal dominant mutation causes complicated hereditary spastic paraplegia in a large family.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {45}, number = {9}, pages = {4373-4381}, pmid = {38607533}, issn = {1590-3478}, support = {PE0000006//Italian Ministry for University and Research/ ; }, mesh = {Humans ; *Spastic Paraplegia, Hereditary/genetics ; Female ; Male ; *Pedigree ; Adult ; *Membrane Proteins/genetics ; *Mutation ; Middle Aged ; Phenotype ; Young Adult ; Adolescent ; Genes, Dominant ; Child ; Aged ; }, abstract = {BACKGROUND: SPG18 is caused by mutations in the endoplasmic reticulum lipid raft associated 2 (ERLIN2) gene. Autosomal recessive (AR) mutations are usually associated with complicated hereditary spastic paraplegia (HSP), while autosomal dominant (AD) mutations use to cause pure SPG18.

AIM: To define the variegate clinical spectrum of the SPG18 and to evaluate a dominant negative effect of erlin2 (encoded by ERLIN2) on oligomerization as causing differences between AR and AD phenotypes.

METHODS: In a four-generation pedigree with an AD pattern, a spastic paraplegia multigene panel test was performed. Oligomerization of erlin2 was analyzed with velocity gradient assay in fibroblasts of the proband and healthy subjects.

RESULTS: Despite the common p.V168M mutation identified in ERLIN2, a phenoconversion to amyotrophic lateral sclerosis (ALS) was observed in the second generation, pure HSP in the third generation, and a complicated form with psychomotor delay and epilepsy in the fourth generation. Erlin2 oligomerization was found to be normal.

DISCUSSION: We report the first AD SPG18 family with a complicated phenotype, and we ruled out a dominant negative effect of V168M on erlin2 oligomerization. Therefore, our data do not support the hypothesis of a relationship between the mode of inheritance and the phenotype, but confirm the multifaceted nature of SPG18 on both genetic and clinical point of view. Clinicians should be aware of the importance of conducting an in-depth clinical evaluation to unmask all the possible manifestations associated to an only apparently pure SPG18 phenotype. We confirm the genotype-phenotype correlation between V168M and ALS emphasizing the value of close follow-up.}, } @article {pmid38607083, year = {2024}, author = {Tamberi, L and Belloni, A and Pugnaloni, A and Rippo, MR and Olivieri, F and Procopio, AD and Bronte, G}, title = {The Influence of Myeloid-Derived Suppressor Cell Expansion in Neuroinflammation and Neurodegenerative Diseases.}, journal = {Cells}, volume = {13}, number = {7}, pages = {}, pmid = {38607083}, issn = {2073-4409}, mesh = {Humans ; *Myeloid-Derived Suppressor Cells/pathology ; Neuroinflammatory Diseases ; *Neurodegenerative Diseases/pathology ; Inflammation/pathology ; Cell Proliferation ; }, abstract = {The neuro-immune axis has a crucial function both during physiological and pathological conditions. Among the immune cells, myeloid-derived suppressor cells (MDSCs) exert a pivotal role in regulating the immune response in many pathological conditions, influencing neuroinflammation and neurodegenerative disease progression. In chronic neuroinflammation, MDSCs could lead to exacerbation of the inflammatory state and eventually participate in the impairment of cognitive functions. To have a complete overview of the role of MDSCs in neurodegenerative diseases, research on PubMed for articles using a combination of terms made with Boolean operators was performed. According to the search strategy, 80 papers were retrieved. Among these, 44 papers met the eligibility criteria. The two subtypes of MDSCs, monocytic and polymorphonuclear MDSCs, behave differently in these diseases. The initial MDSC proliferation is fundamental for attenuating inflammation in Alzheimer's disease (AD), Parkinson's disease (PD), and multiple sclerosis (MS), but not in amyotrophic lateral sclerosis (ALS), where MDSC expansion leads to exacerbation of the disease. Moreover, the accumulation of MDSC subtypes in distinct organs changes during the disease. The proliferation of MDSC subtypes occurs at different disease stages and can influence the progression of each neurodegenerative disorder differently.}, } @article {pmid38606777, year = {2024}, author = {Babu, S and Nicholson, KA and Rothstein, JD and Swenson, A and Sampognaro, PJ and Pant, P and Macklin, EA and Spruill, S and Paganoni, S and Gendron, TF and Prudencio, M and Petrucelli, L and Nix, D and Landrette, S and Nkrumah, E and Fandrick, K and Edwards, J and Young, PR}, title = {Apilimod dimesylate in C9orf72 amyotrophic lateral sclerosis: a randomized phase 2a clinical trial.}, journal = {Brain : a journal of neurology}, volume = {147}, number = {9}, pages = {2998-3008}, doi = {10.1093/brain/awae109}, pmid = {38606777}, issn = {1460-2156}, support = {//OrphAI Therapeutics/ ; }, mesh = {Humans ; Male ; Female ; Middle Aged ; *Amyotrophic Lateral Sclerosis/drug therapy/genetics ; Double-Blind Method ; Adult ; Aged ; *C9orf72 Protein/genetics ; Pyrazoles/therapeutic use/pharmacokinetics ; Treatment Outcome ; Biomarkers/blood ; Hydrazones ; Morpholines ; Pyrimidines ; }, abstract = {Apilimod dimesylate is a first-in-class phosphoinositide kinase, FYVE-type zinc finger-containing (PIKfyve) inhibitor with a favourable clinical safety profile and has demonstrated activity in preclinical C9orf72 and TDP-43 amyotrophic lateral sclerosis (ALS) models. In this ALS clinical trial, the safety, tolerability, CNS penetrance and modulation of pharmacodynamic target engagement biomarkers were evaluated. This phase 2a, randomized, double-blind, placebo-controlled, biomarker-end-point clinical trial was conducted in four US centres (ClinicalTrials.gov NCT05163886). Participants with C9orf72 repeat expansions were randomly assigned (2:1) to receive twice-daily oral treatment with 125 mg apilimod dimesylate capsules or matching placebo for 12 weeks, followed by a 12-week open-label extension. Safety was measured as the occurrence of treatment-emergent or serious adverse events attributable to the study drug and tolerability at trial completion or treatment over 12 weeks. Changes from baseline in plasma and CSF and concentrations of apilimod dimesylate and its active metabolites and of pharmacodynamic biomarkers of PIKfyve inhibition [soluble glycoprotein nonmetastatic melanoma protein B (sGPNMB) upregulation] and disease-specific CNS target engagement [poly(GP)] were measured. Between 16 December 2021 and 7 July 2022, 15 eligible participants were enrolled. There were no drug-related serious adverse events reported in the trial. Fourteen (93%) participants completed the double-blind period with 99% dose compliance [n = 9 (90%) apilimod dimesylate; n = 5 (100%) placebo]. At Week 12, apilimod dimesylate was measurable in CSF at 1.63 ng/ml [standard deviation (SD): 0.937]. At Week 12, apilimod dimesylate increased plasma sGPNMB by >2.5-fold (P < 0.001), indicating PIKfyve inhibition, and lowered CSF poly(GP) protein levels by 73% (P < 0.001), indicating CNS tissue-level proof of mechanism. Apilimod dimesylate met prespecified key safety and biomarker end-points in this phase 2a trial and demonstrated CNS penetrance and pharmacodynamic target engagement. Apilimod dimesylate was observed to result in the greatest reduction in CSF poly(GP) levels observed to date in C9orf72 clinical trials.}, } @article {pmid38606235, year = {2024}, author = {Frolov, A and Guzman, MA and Hayat, G and Martin, JR}, title = {Two Cases of Sporadic Amyotrophic Lateral Sclerosis With Contrasting Clinical Phenotypes: Genetic Insights.}, journal = {Cureus}, volume = {16}, number = {3}, pages = {e56023}, pmid = {38606235}, issn = {2168-8184}, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neuromuscular disease that affects individuals of diverse racial and ethnic backgrounds. There is currently no cure for ALS, and the number of efficient disease-modifying drugs for ALS is limited to a few, despite the large number of clinical trials conducted in recent years. The latter could be attributed to the significant heterogeneity of ALS clinical phenotypes even in their familial forms. To address this issue, we conducted postmortem genetic screening of two female patients with sporadic ALS (sALS) and contrasting clinical phenotypes. The results demonstrated that despite their contrasting clinical phenotypes, both patients had rare pathologic/deleterious mutations in five genes: ACSM5, BBS12, HLA-DQB1, MUC20, and OBSCN, with mutations in three of those genes being identical: BBS12, HLA-DQB1, and MUC20. Additional groups of mutated genes linked to ALS, other neurologic disorders, and ALS-related pathologies were also identified. These data are consistent with a hypothesis that an individual could be primed for ALS via mutations in a specific set of genes not directly linked to ALS. The disease could be initiated by a concerted action of several mutated genes linked to ALS and the disease's clinical phenotype will evolve further through accessory gene mutations associated with other neurological disorders and ALS-related pathologies.}, } @article {pmid38605366, year = {2024}, author = {Aragón-González, A and Shaw, AC and Kok, JR and Roussel, FS and Santos Souza, CD and Granger, SM and Vetter, T and de Diego, Y and Meyer, KC and Beal, SN and Shaw, PJ and Ferraiuolo, L}, title = {C9ORF72 patient-derived endothelial cells drive blood-brain barrier disruption and contribute to neurotoxicity.}, journal = {Fluids and barriers of the CNS}, volume = {21}, number = {1}, pages = {34}, pmid = {38605366}, issn = {2045-8118}, support = {MR/W00416X/1/MRC_/Medical Research Council/United Kingdom ; 765704//Horizon 2020/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics ; *Blood-Brain Barrier/metabolism ; C9orf72 Protein/genetics/metabolism ; *Endothelial Cells/metabolism ; }, abstract = {The blood-brain barrier (BBB) serves as a highly intricate and dynamic interface connecting the brain and the bloodstream, playing a vital role in maintaining brain homeostasis. BBB dysfunction has been associated with multiple neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS); however, the role of the BBB in neurodegeneration is understudied. We developed an ALS patient-derived model of the BBB by using cells derived from 5 patient donors carrying C9ORF72 mutations. Brain microvascular endothelial-like cells (BMEC-like cells) derived from C9ORF72-ALS patients showed altered gene expression, compromised barrier integrity, and increased P-glycoprotein transporter activity. In addition, mitochondrial metabolic tests demonstrated that C9ORF72-ALS BMECs display a significant decrease in basal glycolysis accompanied by increased basal and ATP-linked respiration. Moreover, our study reveals that C9-ALS derived astrocytes can further affect BMECs function and affect the expression of the glucose transporter Glut-1. Finally, C9ORF72 patient-derived BMECs form leaky barriers through a cell-autonomous mechanism and have neurotoxic properties towards motor neurons.}, } @article {pmid38603949, year = {2024}, author = {Shin-Yi Lin, C and Howells, J and Rutkove, S and Nandedkar, S and Neuwirth, C and Noto, YI and Shahrizaila, N and Whittaker, RG and Bostock, H and Burke, D and Tankisi, H}, title = {Neurophysiological and imaging biomarkers of lower motor neuron dysfunction in motor neuron diseases/amyotrophic lateral sclerosis: IFCN handbook chapter.}, journal = {Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology}, volume = {162}, number = {}, pages = {91-120}, doi = {10.1016/j.clinph.2024.03.015}, pmid = {38603949}, issn = {1872-8952}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology/diagnostic imaging ; *Motor Neurons/physiology ; *Motor Neuron Disease/physiopathology/diagnostic imaging/diagnosis ; *Biomarkers ; *Electromyography/methods ; *Neural Conduction/physiology ; }, abstract = {This chapter discusses comprehensive neurophysiological biomarkers utilised in motor neuron disease (MND) and, in particular, its commonest form, amyotrophic lateral sclerosis (ALS). These encompass the conventional techniques including nerve conduction studies (NCS), needle and high-density surface electromyography (EMG) and H-reflex studies as well as novel techniques. In the last two decades, new methods of assessing the loss of motor units in a muscle have been developed, that are more convenient than earlier methods of motor unit number estimation (MUNE),and may use either electrical stimulation (e.g. MScanFit MUNE) or voluntary activation (MUNIX). Electrical impedance myography (EIM) is another novel approach for the evaluation that relies upon the application and measurement of high-frequency, low-intensity electrical current. Nerve excitability techniques (NET) also provide insights into the function of an axon and reflect the changes in resting membrane potential, ion channel dysfunction and the structural integrity of the axon and myelin sheath. Furthermore, imaging ultrasound techniques as well as magnetic resonance imaging are capable of detecting the constituents of morphological changes in the nerve and muscle. The chapter provides a critical description of the ability of each technique to provide neurophysiological insight into the complex pathophysiology of MND/ALS. However, it is important to recognise the strengths and limitations of each approach in order to clarify utility. These neurophysiological biomarkers have demonstrated reliability, specificity and provide additional information to validate and assess lower motor neuron dysfunction. Their use has expanded the knowledge about MND/ALS and enhanced our understanding of the relationship between motor units, axons, reflexes and other neural circuits in relation to clinical features of patients with MND/ALS at different stages of the disease. Taken together, the ultimate goal is to aid early diagnosis, distinguish potential disease mimics, monitor and stage disease progression, quantify response to treatment and develop potential therapeutic interventions.}, } @article {pmid38602336, year = {2024}, author = {Zhang, QJ and Lin, J and Wang, YL and Chen, L and Ding, Y and Zheng, FZ and Song, HH and Lv, AW and Li, YY and Guo, QF and Lin, MT and Hu, W and Xu, LQ and Zhao, WL and Fang, L and Cui, MC and Fu, ZF and Chen, WJ and Zhang, J and Wang, ZQ and Wang, N and Fu, Y}, title = {Detection of pTDP-43 via routine muscle biopsy: A promising diagnostic biomarker for amyotrophic lateral sclerosis.}, journal = {Brain pathology (Zurich, Switzerland)}, volume = {34}, number = {6}, pages = {e13261}, pmid = {38602336}, issn = {1750-3639}, support = {2020Y9129//Joint Funds for the Innovation of Science and Technology of Fujian Province/ ; 2021J01209//Joint Funds for the Innovation of Science and Technology of Fujian Province/ ; 2021Y9156//Joint Funds for the Innovation of Science and Technology of Fujian Province/ ; BPB-LMT2021//2021 Provincial Special Subsidy Funds for Health (Biobank Construction Project for Neurological Diseases)/ ; 82230039//National Natural Science Foundation of China/ ; 82371409//National Natural Science Foundation of China/ ; U2005201//National Natural Science Foundation of China/ ; U21A20360//National Natural Science Foundation of China/ ; 2022ZQNZD005//Major Scientific Research Program for Young and Middle-aged Health Professionals of Fujian Province/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/pathology/diagnosis/genetics/metabolism ; Male ; Female ; Middle Aged ; Aged ; *Biomarkers/metabolism ; *DNA-Binding Proteins/metabolism ; Biopsy/methods ; *Muscle, Skeletal/pathology/metabolism ; Adult ; C9orf72 Protein/genetics ; Cohort Studies ; Phosphorylation ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease, pathologically characterized by TDP-43 aggregates. Recent evidence has been indicated that phosphorylated TDP-43 (pTDP-43) is present not only in motor neurons but also in muscle tissues. However, it is unclear whether testing pTDP-43 aggregation in muscle tissue would assist in the diagnosis of ALS. We propose three key questions: (i) Is aggregation of pTDP-43 detectable in routine biopsied muscles? (ii) Can detection of pTDP-43 aggregation discriminate between ALS and non-ALS patients? (iii) Can pTDP-43 aggregation be observed in the early stages of ALS? We conducted a diagnostic study comprising 2 groups: an ALS group in which 18 cases underwent muscle biopsy screened from a registered ALS cohort consisting of 802 patients and a non-ALS control group, in which we randomly selected 54 muscle samples from a biospecimen bank of 684 patients. Among the 18 ALS patients, 3 patients carried pathological GGGGCC repeats in the C9ORF72 gene, 2 patients carried SOD1 mutations, and 7 patients were at an early stage with only one body region clinically affected. The pTDP-43 accumulation could be detected in routine biopsied muscles, including biceps brachii, deltoid, tibialis anterior, and quadriceps. Abnormal aggregation of pTDP-43 was present in 94.4% of ALS patients (17/18) compared to 29.6% of non-ALS controls (16/54; p < 0.001). The pTDP-43 aggregates were mainly close to the sarcolemma. Using a semi-quantified pTDP-43 aggregates score, we applied a cut-off value of 3 as a diagnostic biomarker, resulting in a sensitivity of 94.4% and a specificity of 83.3%. Moreover, we observed that accumulation of pTDP-43 occurred in muscle tissues prior to clinical symptoms and electromyographic lesions. Our study provides proof-of-concept for the detection of pTDP-43 accumulation via routine muscle biopsy which may serve as a novel biomarker for diagnosis of ALS.}, } @article {pmid38601850, year = {2024}, author = {Xiao, C and Gu, X and Feng, Y and Shen, J}, title = {Two-sample Mendelian randomization analysis of 91 circulating inflammatory protein levels and amyotrophic lateral sclerosis.}, journal = {Frontiers in aging neuroscience}, volume = {16}, number = {}, pages = {1367106}, pmid = {38601850}, issn = {1663-4365}, abstract = {INTRODUCTION: Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease with poorly understood pathophysiology. Recent studies have highlighted systemic inflammation, especially the role of circulating inflammatory proteins, in ALS.

METHODS: This study investigates the potential causal link between these proteins and ALS. We employed a two-sample Mendelian Randomization(MR) approach, analyzing data from large-scale genome-wide association studies to explore the relationship between 91 circulating inflammatory proteins and ALS. This included various MR methods like MR Egger, weighted median, and inverse-variance weighted, complemented by sensitivity analyses for robust results.

RESULTS: Significant associations were observed between levels of inflammatory proteins, including Adenosine Deaminase, Interleukin-17C, Oncostatin-M, Leukemia Inhibitory Factor Receptor, and Osteoprotegerin, and ALS risk. Consistencies were noted across different P-value thresholds. Bidirectional MR suggested that ALS risk might influence levels of certain inflammatory proteins.

DISCUSSION: Our findings, via MR analysis, indicate a potential causal relationship between circulating inflammatory proteins and ALS. This sheds new light on ALS pathophysiology and suggests possible therapeutic targets. Further research is required to confirm these results and understand the specific roles of these proteins in ALS.}, } @article {pmid38601572, year = {2024}, author = {Urigüen, JA and Ruiz de Gauna, S and Gutiérrez, JJ and Azcárate, I and Leturiondo, M and Redondo, K and Russell, JK and Daya, MR}, title = {Metrics of impulsiveness of manual chest compressions for out-of-hospital cardiopulmonary resuscitation.}, journal = {Heliyon}, volume = {10}, number = {7}, pages = {e28739}, pmid = {38601572}, issn = {2405-8440}, abstract = {AIM: Propose new metrics of impulsiveness of manual chest compressions (CCs) that account for shape and duration, separate the characteristics of the compressive part of the CC cycle from those of the recoil part, and are uncorrelated to CC depth and rate.

METHODS: We conducted a retrospective analysis of adult out-of-hospital cardiac arrest monitor-defibrillator recordings having CPR data. Specifically, episodes of adult patients with ≥ 1000 compressions free of leaning were examined. CCs were obtained from the depth signal of the valid episodes, and we calculated the novel metrics: compression area index (CAI), recoil area index (RAI), compression impulsiveness index (CII) and recoil impulsiveness index (RII). Generalized linear mixed-effects models and Jonckheere-Terpstra trend analyses were employed to measure differences between populations and trends, and the absolute value of Pearson's correlation coefficient |r| was used to report dependence between variables. Statistics are reported as median and interquartile range.

RESULTS: We analyzed 982,340 CCs corresponding to 453 episodes, for which we calculated their CAI, RAI and duty cycle (DC). We analyzed the metrics for various populations: age, sex, any ROSC achieved and disposition, and found that CAI was significantly different according to patient disposition and RAI relative to age and sex (p<0.05). None of the metrics was correlated strongly to depth or rate (|r| values of 0.22 or smaller), and all of them varied for CC series corresponding to the same rescuer over the course of resuscitation (ptrend<0.05). However, we observed that the metrics are not balanced, in that for any value of DC, CAI and RAI span almost their entire ranges.

CONCLUSION: The proposed metrics correctly and completely describe manual CC waveforms, improve upon the DC, since they depend on the signal waveform, and provide additional information to current indicators of quality CPR, depth and rate. Furthermore, they allow to differentiate the compressive and recoil parts of the CC cycle, reflecting influence of the rescuer (via CAI or CII) and of the biomechanics of the patient's chest (via RAI or RII). Thus, they have the potential to contribute to better understanding CPR dynamics and, eventually, to enhanced quality of CPR practice as additional indicators of proper manual CC technique.}, } @article {pmid38601155, year = {2024}, author = {Du, R and Chen, P and Li, M and Zhu, Y and He, Z and Huang, X}, title = {Developing a novel immune infiltration-associated mitophagy prediction model for amyotrophic lateral sclerosis using bioinformatics strategies.}, journal = {Frontiers in immunology}, volume = {15}, number = {}, pages = {1360527}, pmid = {38601155}, issn = {1664-3224}, mesh = {Animals ; Mice ; Humans ; *Amyotrophic Lateral Sclerosis/genetics ; Mitophagy/genetics ; *Neurodegenerative Diseases ; Computational Biology ; Databases, Factual ; Disease Models, Animal ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease, which leads to muscle weakness and eventual paralysis. Numerous studies have indicated that mitophagy and immune inflammation have a significant impact on the onset and advancement of ALS. Nevertheless, the possible diagnostic and prognostic significance of mitophagy-related genes associated with immune infiltration in ALS is uncertain. The purpose of this study is to create a predictive model for ALS using genes linked with mitophagy-associated immune infiltration.

METHODS: ALS gene expression profiles were downloaded from the Gene Expression Omnibus (GEO) database. Univariate Cox analysis and machine learning methods were applied to analyze mitophagy-associated genes and develop a prognostic risk score model. Subsequently, functional and immune infiltration analyses were conducted to study the biological attributes and immune cell enrichment in individuals with ALS. Additionally, validation of identified feature genes in the prediction model was performed using ALS mouse models and ALS patients.

RESULTS: In this study, a comprehensive analysis revealed the identification of 22 mitophagy-related differential expression genes and 40 prognostic genes. Additionally, an 18-gene prognostic signature was identified with machine learning, which was utilized to construct a prognostic risk score model. Functional enrichment analysis demonstrated the enrichment of various pathways, including oxidative phosphorylation, unfolded proteins, KRAS, and mTOR signaling pathways, as well as other immune-related pathways. The analysis of immune infiltration revealed notable distinctions in certain congenital immune cells and adaptive immune cells between the low-risk and high-risk groups, particularly concerning the T lymphocyte subgroup. ALS mouse models and ALS clinical samples demonstrated consistent expression levels of four mitophagy-related immune infiltration genes (BCKDHA, JTB, KYNU, and GTF2H5) with the results of bioinformatics analysis.

CONCLUSION: This study has successfully devised and verified a pioneering prognostic predictive risk score for ALS, utilizing eighteen mitophagy-related genes. Furthermore, the findings indicate that four of these genes exhibit promising roles in the context of ALS prognostic.}, } @article {pmid38601118, year = {2024}, author = {Patel, GD and Liu, L and Li, A and Yang, YH and Shen, CC and Brand-Saberi, B and Yang, X}, title = {Mesenchymal stem cell-based therapies for treating well-studied neurological disorders: a systematic review.}, journal = {Frontiers in medicine}, volume = {11}, number = {}, pages = {1361723}, pmid = {38601118}, issn = {2296-858X}, abstract = {BACKGROUND: Millions of people across the globe are affected by conditions like Amyotrophic Lateral Sclerosis (ALS), Parkinson's Disease (PD), Multiple Sclerosis (MS), Spinal Cord Injury (SCI), and Traumatic Brain Injury (TBI), although most occurrences are common in the elderly population. This systematic review aims to highlight the safety of the procedures, their tolerability, and efficacy of the available therapies conducted over the years using mesenchymal stem cells (MSCs) in treating the neurological conditions mentioned above.

METHODS: PubMed was used to search for published data from clinical trials performed using mesenchymal stem cells. Studies that provided the necessary information that mentioned the efficacy and adverse effects of the treatment in patients were considered for this review.

RESULTS: In total, 43 manuscripts were selected after a strategic search, and these studies have been included in this systematic review. Most included studies reported the safety of the procedures used and the treatment's good tolerability, with mild adverse events such as fever, headache, mild pain at the injection site, or nausea being common. A few studies also reported death of some patients, attributed to the progression of the disease to severe stages before the treatment. Other severe events, such as respiratory or urinary infections reported in some studies, were not related to the treatment. Different parameters were used to evaluate the efficacy of the treatment based on the clinical condition of the patient.

CONCLUSION: Mesenchymal stem cells transplantation has so far proven to be safe and tolerable in select studies and patient types. This systematic review includes the results from the 43 selected studies in terms of safety and tolerability of the procedures, and several adverse events and therapeutic benefits during the follow-up period after administration of MSCs.}, } @article {pmid38600725, year = {2024}, author = {Madhubala, D and Patra, A and Khan, MR and Mukherjee, AK}, title = {Phytomedicine for neurodegenerative diseases: The road ahead.}, journal = {Phytotherapy research : PTR}, volume = {38}, number = {6}, pages = {2993-3019}, doi = {10.1002/ptr.8192}, pmid = {38600725}, issn = {1099-1573}, support = {//IASST/ ; EMR/2017/001829//Science and Engineering Research Board/ ; }, mesh = {Humans ; *Neurodegenerative Diseases/drug therapy ; *Catechin/analogs & derivatives/therapeutic use/pharmacology ; *Phytotherapy ; Curcumin/therapeutic use/pharmacology ; Quercetin/pharmacology/therapeutic use ; Animals ; Cannabinoids/therapeutic use/pharmacology ; Apigenin/pharmacology/therapeutic use ; Blood-Brain Barrier/drug effects ; Phytochemicals/pharmacology/therapeutic use ; Plant Extracts/therapeutic use/pharmacology ; }, abstract = {Neurodegenerative disorders (NDs) are among the most common causes of death across the globe. NDs are characterized by progressive damage to CNS neurons, leading to defects in specific brain functions such as memory, cognition, and movement. The most common NDs are Parkinson's, Alzheimer's, Huntington's, and amyotrophic lateral sclerosis (ALS). Despite extensive research, no therapeutics or medications against NDs have been proven to be effective. The current treatment of NDs involving symptom-based targeting of the disease pathogenesis has certain limitations, such as drug resistance, adverse side effects, poor blood-brain barrier permeability, and poor bioavailability of drugs. Some studies have shown that plant-derived natural compounds hold tremendous promise for treating and preventing NDs. Therefore, the primary objective of this review article is to critically analyze the properties and potency of some of the most studied phytomedicines, such as quercetin, curcumin, epigallocatechin gallate (EGCG), apigenin, and cannabinoids, and highlight their advantages and limitations for developing next-generation alternative treatments against NDs. Further extensive research on pre-clinical and clinical studies for developing plant-based drugs against NDs from bench to bedside is warranted.}, } @article {pmid38600555, year = {2024}, author = {Liu, Y and Yan, D and Yang, L and Chen, X and Hu, C and Chen, M}, title = {Stathmin 2 is a potential treatment target for TDP-43 proteinopathy in amyotrophic lateral sclerosis.}, journal = {Translational neurodegeneration}, volume = {13}, number = {1}, pages = {20}, pmid = {38600555}, issn = {2047-9158}, support = {2023A1515010477//Guangdong Basic and Applied Basic Research Foundation/ ; 32000690//National Natural Science Foundation of China/ ; 2019B030335001//The Key-Area Research and Development Program of Guangdong Province,China/ ; 2023-Z04-103//The Key Medical and Health Projects of Panyu District Science and Technology Plan/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/complications ; DNA-Binding Proteins/genetics ; *Stathmin/antagonists & inhibitors ; *TDP-43 Proteinopathies/drug therapy ; }, } @article {pmid38599171, year = {2024}, author = {Castro-Gomez, S and Heneka, MT}, title = {Innate immune activation in neurodegenerative diseases.}, journal = {Immunity}, volume = {57}, number = {4}, pages = {790-814}, doi = {10.1016/j.immuni.2024.03.010}, pmid = {38599171}, issn = {1097-4180}, mesh = {Humans ; *Neurodegenerative Diseases ; Receptors, Pattern Recognition ; Immune System ; Inflammation Mediators ; Immunity, Innate ; }, abstract = {Activation of the innate immune system following pattern recognition receptor binding has emerged as one of the major pathogenic mechanisms in neurodegenerative disease. Experimental, epidemiological, pathological, and genetic evidence underscores the meaning of innate immune activation during the prodromal as well as clinical phases of several neurodegenerative disorders including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and frontotemporal dementia. Importantly, innate immune activation and the subsequent release of inflammatory mediators contribute mechanistically to other hallmarks of neurodegenerative diseases such as aberrant proteostatis, pathological protein aggregation, cytoskeleton abnormalities, altered energy homeostasis, RNA and DNA defects, and synaptic and network disbalance and ultimately to the induction of neuronal cell death. In this review, we discuss common mechanisms of innate immune activation in neurodegeneration, with particular emphasis on the pattern recognition receptors (PRRs) and other receptors involved in the detection of damage-associated molecular patterns (DAMPs).}, } @article {pmid38598868, year = {2024}, author = {Zhan, Y and Liu, H and Cao, Z and Qi, J and Bai, L and Pan, L}, title = {Target-site and non-target-site resistance mechanisms confer mesosulfuron-methyl resistance in Alopecurus aequalis.}, journal = {Plant physiology and biochemistry : PPB}, volume = {210}, number = {}, pages = {108597}, doi = {10.1016/j.plaphy.2024.108597}, pmid = {38598868}, issn = {1873-2690}, mesh = {*Herbicide Resistance/genetics ; *Sulfonylurea Compounds/pharmacology ; *Acetolactate Synthase/genetics/metabolism ; *Herbicides/pharmacology ; *Poaceae/genetics/drug effects/metabolism ; Cytochrome P-450 Enzyme System/genetics/metabolism ; Plant Proteins/genetics/metabolism ; Glutathione Transferase/metabolism/genetics ; Imidazoles/pharmacology ; Gene Expression Regulation, Plant/drug effects ; Mutation ; Molecular Docking Simulation ; Benzoates ; Pyrimidines ; }, abstract = {BACKGROUND: Shortawn foxtail (Alopecurus aequalis Sobol.) is a noxious weed in China. The resistance of A. aequalis developed rapidly due to the long-term application of acetolactate synthase (ALS)-inhibiting herbicides. Here, a suspected mesosulfuron-methyl-resistant A. aequalis population, Aa-R, was collected from a wheat field in China.

RESULTS: A dose‒response test showed that the Aa-R population has evolved a high level of resistance to mesosulfuron-methyl, and its growth was suppressed by imazamox, pyroxsulam and bispyribac-sodium. ALS gene sequence analysis revealed that a known resistance-related mutation (Pro-197-Thr) was present in the Aa-R population. Moreover, ALS gene overexpression was detected in the Aa-R population. The mesosulfuron-methyl resistance could be reversed by cytochrome P450 monooxygenase (CYP450) and glutathione S-transferase (GST) inhibitors. In addition, enhanced metabolism of mesosulfuron-methyl was detected in the Aa-R population compared with the susceptible population. NADPH-cytochrome P450 reductase and GST activities were strongly inducible in the Aa-R population. One CYP450 gene, CYP74A2, and one GST gene, GST4, were constitutively upregulated in the Aa-R population. Molecular docking results showed the binding affinity of CYP74A2 and GST4 for the tested ALS-inhibiting herbicides, respectively.

CONCLUSION: This study confirmed that target-site resistance and non-target-site resistance involving CYP450 and GST were the main mechanisms involved in resistance in the mesosulfuron-methyl-resistant A. aequalis population.}, } @article {pmid38598318, year = {2024}, author = {Peng, J and Gao, S and Bi, JH and Shi, J and Jia, L and Pang, QF and Zhao, DM and Fu, Y and Ye, F}, title = {Design, Synthesis, and Biological Evaluation of Novel Purine Derivatives as Herbicide Safeners.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.3c08138}, pmid = {38598318}, issn = {1520-5118}, abstract = {Mesosulfuron-methyl, an inhibitor of acetolactate synthase (ALS), has been extensively used in wheats. However, it can damage wheat (Triticum aestivum) and even lead to crop death. Herbicide safeners selectively shield crops from such damage without compromising weed control. To mitigate the phytotoxicity of mesosulfuron-methyl in crops, several purine derivatives were developed based on active substructure splicing. The synthesized title compounds underwent thorough characterization using infrared spectroscopy, [1]H nuclear magnetic resonance ([1]H NMR), [13]C nuclear magnetic resonance ([13]C NMR), and high-resolution mass spectrometry. We evaluated chlorophyll and glutathione contents as well as various enzyme activities to evaluate the safer activity of these compounds. Compounds III-3 and III-7 exhibited superior activity compared with the safener mefenpyr-diethyl. Molecular structure analysis, along with predictions of absorption, distribution, metabolism, excretion, and toxicity, indicated that compound III-7 shared pharmacokinetic traits with the commercial safener mefenpyr-diethyl. Molecular docking simulations revealed that compound III-7 competitively bound to the ALS active site with mesosulfuron-methyl, elucidating the protective mechanism of the safeners. Overall, this study highlights purine derivatives as potential candidates for novel safener development.}, } @article {pmid38597682, year = {2024}, author = {Kojak, N and Kuno, J and Fittipaldi, KE and Khan, A and Wenger, D and Glasser, M and Donnianni, RA and Tang, Y and Zhang, J and Huling, K and Ally, R and Mujica, AO and Turner, T and Magardino, G and Huang, PY and Kerk, SY and Droguett, G and Prissette, M and Rojas, J and Gomez, T and Gagliardi, A and Hunt, C and Rabinowitz, JS and Gong, G and Poueymirou, W and Chiao, E and Zambrowicz, B and Siao, CJ and Kajimura, D}, title = {Somatic and intergenerational G4C2 hexanucleotide repeat instability in a human C9orf72 knock-in mouse model.}, journal = {Nucleic acids research}, volume = {52}, number = {10}, pages = {5732-5755}, pmid = {38597682}, issn = {1362-4962}, mesh = {Animals ; Humans ; Mice ; Amyotrophic Lateral Sclerosis/genetics ; *C9orf72 Protein/genetics ; Disease Models, Animal ; DNA Breaks, Double-Stranded ; *DNA Repeat Expansion/genetics ; Frontotemporal Dementia/genetics ; Gene Knock-In Techniques ; *Genomic Instability/genetics ; MutS Homolog 2 Protein/genetics ; }, abstract = {Expansion of a G4C2 repeat in the C9orf72 gene is associated with familial Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD). To investigate the underlying mechanisms of repeat instability, which occurs both somatically and intergenerationally, we created a novel mouse model of familial ALS/FTD that harbors 96 copies of G4C2 repeats at a humanized C9orf72 locus. In mouse embryonic stem cells, we observed two modes of repeat expansion. First, we noted minor increases in repeat length per expansion event, which was dependent on a mismatch repair pathway protein Msh2. Second, we found major increases in repeat length per event when a DNA double- or single-strand break (DSB/SSB) was artificially introduced proximal to the repeats, and which was dependent on the homology-directed repair (HDR) pathway. In mice, the first mode primarily drove somatic repeat expansion. Major changes in repeat length, including expansion, were observed when SSB was introduced in one-cell embryos, or intergenerationally without DSB/SSB introduction if G4C2 repeats exceeded 400 copies, although spontaneous HDR-mediated expansion has yet to be identified. These findings provide a novel strategy to model repeat expansion in a non-human genome and offer insights into the mechanism behind C9orf72 G4C2 repeat instability.}, } @article {pmid38596778, year = {2024}, author = {Ramírez-Jarquín, JO and Tecalco-Cruz, AC and Lopez-Huerta, VG and Ramírez-Jarquín, UN}, title = {Editorial: Over 60 years of neurochemistry, the heritage of Dr. Ricardo Tapia.}, journal = {Frontiers in molecular neuroscience}, volume = {17}, number = {}, pages = {1398127}, doi = {10.3389/fnmol.2024.1398127}, pmid = {38596778}, issn = {1662-5099}, } @article {pmid38596666, year = {2024}, author = {Sini, P and Galleri, G and Ciampelli, C and Galioto, M and Padedda, BM and Lugliè, A and Iaccarino, C and Crosio, C}, title = {Evaluation of cyanotoxin L-BMAA effect on α-synuclein and TDP43 proteinopathy.}, journal = {Frontiers in immunology}, volume = {15}, number = {}, pages = {1360068}, pmid = {38596666}, issn = {1664-3224}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/pathology ; alpha-Synuclein ; Cyanobacteria Toxins ; *Amino Acids, Diamino/toxicity ; *Parkinson Disease ; *Cyanobacteria ; }, abstract = {The complex interplay between genetic and environmental factors is considered the cause of neurodegenerative diseases including Parkinson's disease (PD) and Amyotrophic Lateral Sclerosis (ALS). Among the environmental factors, toxins produced by cyanobacteria have received much attention due to the significant increase in cyanobacteria growth worldwide. In particular, L-BMAA toxin, produced by diverse taxa of cyanobacteria, dinoflagellates and diatoms, has been extensively correlated to neurodegeneration. The molecular mechanism of L-BMAA neurotoxicity is still cryptic and far from being understood. In this research article, we have investigated the molecular pathways altered by L-BMAA exposure in cell systems, highlighting a significant increase in specific stress pathways and an impairment in autophagic processes. Interestingly, these changes lead to the accumulation of both α-synuclein and TDP43, which are correlated with PD and ALS proteinopathy, respectively. Finally, we were able to demonstrate specific alterations of TDP43 WT or pathological mutants with respect to protein accumulation, aggregation and cytoplasmic translocation, some of the typical features of both sporadic and familial ALS.}, } @article {pmid38596495, year = {2024}, author = {Dirjayanto, VJ and Audrey, J and Simadibrata, DM}, title = {Vonoprazan-amoxicillin dual regimen with Saccharomyces boulardii as a rescue therapy for Helicobacter pylori: Current perspectives and implications.}, journal = {World journal of gastroenterology}, volume = {30}, number = {10}, pages = {1280-1286}, pmid = {38596495}, issn = {2219-2840}, mesh = {Humans ; Amoxicillin/therapeutic use ; Anti-Bacterial Agents/adverse effects ; *Helicobacter pylori ; *Saccharomyces boulardii ; *Helicobacter Infections/drug therapy ; Clarithromycin/therapeutic use ; Drug Therapy, Combination ; Proton Pump Inhibitors/adverse effects ; H(+)-K(+)-Exchanging ATPase ; Ions/pharmacology/therapeutic use ; Treatment Outcome ; *Pyrroles ; *Sulfonamides ; }, abstract = {Yu et al's study in the World Journal of Gastroenterology (2023) introduced a novel regimen of Vonoprazan-amoxicillin dual therapy combined with Saccharomyces boulardii (S. boulardii) for the rescue therapy against Helicobacter pylori (H. pylori), a pathogen responsible for peptic ulcers and gastric cancer. Vonoprazan is a potassium-competitive acid blocker renowned for its rapid and long-lasting acid suppression, which is minimally affected by mealtime. Compared to proton pump inhibitors, which bind irreversibly to cysteine residues in the H[+]/K[+]-ATPase pump, Vonoprazan competes with the K[+] ions, prevents the ions from binding to the pump and blocks acid secretion. Concerns with increasing antibiotic resistance, effects on the gut microbiota, patient compliance, and side effects have led to the advent of a dual regimen for H. pylori. Previous studies suggested that S. boulardii plays a role in stabilizing the gut barrier which improves H. pylori eradication rate. With an acceptable safety profile, the dual-adjunct regimen was effective regardless of prior treatment failure and antibiotic resistance profile, thereby strengthening the applicability in clinical settings. Nonetheless, S. boulardii comes in various formulations and dosages, warranting further exploration into the optimal dosage for supplementation in rescue therapy. Additionally, larger, randomized, double-blinded controlled trials are warranted to confirm these promising results.}, } @article {pmid38596011, year = {2024}, author = {Xu, CZ and Huan, X and Luo, SS and Zhong, HH and Zhao, CB and Chen, Y and Zou, ZY and Chen, S}, title = {Serum cytokines profile changes in amyotrophic lateral sclerosis.}, journal = {Heliyon}, volume = {10}, number = {7}, pages = {e28553}, pmid = {38596011}, issn = {2405-8440}, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder, characterized by progressive limb weakness, dysphagia, dysphonia, and respiratory failure due to degeneration of upper and lower motor neurons. The pathogenesis of ALS is still unclear. Neuroinflammation has been found to be involved in its development and progression. Cytokines play a significant role in the inflammatory process. This study aims to identify novel biomarkers that may assist in the diagnosis of ALS.

METHODS: In Fujian Medical University Union Hospital and Huashan Hospital Fudan University, two independent centers, we prospectively recruited 50 ALS patients, and 41 healthy controls (25 ALS and 26 controls in the first stage and 25 ALS and 15 controls in the validation stage). An 18-plex Luminex kit was used to screen the serum cytokines levels in the first stage. Commercial ELISA kits were used to measure the levels of target cytokines in the validation stage. A single-molecule array HD-X platform was applied to assess the levels of serum neurofilament light chain (NFL).

RESULTS: The levels of serum IL-18 were markedly increased in patients with ALS in the first stage (p = 0.016). The ROC curve showed an area under the curve at 0.695 (95% CI 0.50-0.84) in distinguishing ALS patients from healthy controls. The IL-21 was decreased in elderly patients when grouped by 55 years old (the medium age). Furthermore, the IL-5, IL-13, IL-18, and NFL had a positive relationship with the disease progression of ALS. We also found that serum IL-18 was markedly increased in ALS patients in the validation stage (167.67 [148.25-175.59] vs 116.44 [102.43-122.19]pg/ml, p < 0.0015).

CONCLUSION: In this study, we identified systemic cytokine profile changes in the serum of ALS patients, especially the elevated IL-18, as well as the decreased IL-21 in elder patients. These changes in serum cytokine profiles may shed new light on an in-depth understanding of the immunopathogenic characteristics of ALS.}, } @article {pmid38595972, year = {2024}, author = {Zhou, L and Xie, M and Wang, X and Xu, R}, title = {The usage and advantages of several common amyotrophic lateral sclerosis animal models.}, journal = {Frontiers in neuroscience}, volume = {18}, number = {}, pages = {1341109}, pmid = {38595972}, issn = {1662-4548}, abstract = {Amyotrophic lateral sclerosis is a fatal, multigenic, multifactorial neurodegenerative disease characterized by upper and lower motor neuron loss. Animal models are essential for investigating pathogenesis and reflecting clinical manifestations, particularly in developing reasonable prevention and therapeutic methods for human diseases. Over the decades, researchers have established a host of different animal models in order to dissect amyotrophic lateral sclerosis (ALS), such as yeast, worms, flies, zebrafish, mice, rats, pigs, dogs, and more recently, non-human primates. Although these models show different peculiarities, they are all useful and complementary to dissect the pathological mechanisms of motor neuron degeneration in ALS, contributing to the development of new promising therapeutics. In this review, we describe several common animal models in ALS, classified by the naturally occurring and experimentally induced, pointing out their features in modeling, the onset and progression of the pathology, and their specific pathological hallmarks. Moreover, we highlight the pros and cons aimed at helping the researcher select the most appropriate among those common experimental animal models when designing a preclinical ALS study.}, } @article {pmid38595767, year = {2024}, author = {Jia, H and Omar, AA and Xu, J and Dalmendray, J and Wang, Y and Feng, Y and Wang, W and Hu, Z and Grosser, JW and Wang, N}, title = {Generation of transgene-free canker-resistant Citrus sinensis cv. Hamlin in the T0 generation through Cas12a/CBE co-editing.}, journal = {Frontiers in plant science}, volume = {15}, number = {}, pages = {1385768}, pmid = {38595767}, issn = {1664-462X}, abstract = {Citrus canker disease affects citrus production. This disease is caused by Xanthomonas citri subsp. citri (Xcc). Previous studies confirmed that during Xcc infection, PthA4, a transcriptional activator like effector (TALE), is translocated from the pathogen to host plant cells. PthA4 binds to the effector binding elements (EBEs) in the promoter region of canker susceptibility gene LOB1 (EBEPthA4-LOBP) to activate its expression and subsequently cause canker symptoms. Previously, the Cas12a/CBE co-editing method was employed to disrupt EBEPthA4-LOBP of pummelo, which is highly homozygous. However, most commercial citrus cultivars are heterozygous hybrids and more difficult to generate homozygous/biallelic mutants. Here, we employed Cas12a/CBE co-editing method to edit EBEPthA4-LOBP of Hamlin (Citrus sinensis), a commercial heterozygous hybrid citrus cultivar grown worldwide. Binary vector GFP-p1380N-ttLbCas12a:LOBP1-mPBE:ALS2:ALS1 was constructed and shown to be functional via Xcc-facilitated agroinfiltration in Hamlin leaves. This construct allows the selection of transgene-free regenerants via GFP, edits ALS to generate chlorsulfuron-resistant regenerants as a selection marker for genome editing resulting from transient expression of the T-DNA via nCas9-mPBE:ALS2:ALS1, and edits gene(s) of interest (i.e., EBEPthA4-LOBP in this study) through ttLbCas12a, thus creating transgene-free citrus. Totally, 77 plantlets were produced. Among them, 8 plantlets were transgenic plants (#HamGFP1 - #HamGFP8), 4 plantlets were transgene-free (#HamNoGFP1 - #HamNoGFP4), and the rest were wild type. Among 4 transgene-free plantlets, three lines (#HamNoGFP1, #HamNoGFP2 and #HamNoGFP3) contained biallelic mutations in EBEpthA4, and one line (#HamNoGFP4) had homozygous mutations in EBEpthA4. We achieved 5.2% transgene-free homozygous/biallelic mutation efficiency for EBEPthA4-LOBP in C. sinensis cv. Hamlin, compared to 1.9% mutation efficiency for pummelo in a previous study. Importantly, the four transgene-free plantlets and 3 transgenic plantlets that survived were resistant against citrus canker. Taken together, Cas12a/CBE co-editing method has been successfully used to generate transgene-free canker-resistant C. sinensis cv. Hamlin in the T0 generation via biallelic/homozygous editing of EBEpthA4 of the canker susceptibility gene LOB1.}, } @article {pmid38595691, year = {2024}, author = {McMackin, R and Tadjine, Y and Fasano, A and Mitchell, M and Heverin, M and Awiszus, F and Nasseroleslami, B and Carson, RG and Hardiman, O}, title = {Examining short interval intracortical inhibition with different transcranial magnetic stimulation-induced current directions in ALS.}, journal = {Clinical neurophysiology practice}, volume = {9}, number = {}, pages = {120-129}, pmid = {38595691}, issn = {2467-981X}, abstract = {OBJECTIVE: To establish if induced current direction across the motor cortex alters the sensitivity of transcranial magnetic stimulation (TMS)-evoked short-interval intracortical inhibition (SICI) as an ALS biomarker.

METHODS: Threshold tracking-TMS was undertaken in 35 people with ALS and 39 controls. Using a coil orientation which induces posterior-anterior (PA)-directed current across the motor cortex, SICI (1 ms and 3 ms interstimulus intervals) and intracortical facilitation (ICF, 10 ms interstimulus interval) were recorded. SICI3ms was also recorded using a coil orientation which induces anterior-posterior (AP)-directed current across the motor cortex.

RESULTS: At group level, SICI3ms-PA (AUROC = 0.7), SICI3ms-AP (AUROC = 0.8) and SICI1ms (AUROC = 0.66) were substantially lower in those with ALS, although there was considerable interindividual heterogeneity. Averaging across interstimulus intervals (ISIs) marginally improved SICIPA sensitivity (AUROC = 0.76). Averaging SICI values across ISIs and orientations into a single SICI measure did not substantially improve sensitivity (AUROC = 0.81) compared to SICI3ms-AP alone. SICI3ms-AP and SICI3ms-PA did not significantly correlate (rho = 0.19, p = 0.313), while SICI1ms-PA and SICI3ms-PA did (rho = 0.37, p = 0.006). Further, those with ALS with the lowest SICI3ms-PA were not those with the lowest SICI3ms-AP. ICF was similar between groups (AUROC = 0.50).

CONCLUSIONS: SICIPA and SICIAP are uncorrelated measures of motor cortical inhibitory functions which are useful as distinct, unequally affected, measures of disinhibition in ALS.

SIGNIFICANCE: Examining both SICIPA and SICIAP may facilitate more comprehensive characterisation of motor cortical disinhibition in ALS.}, } @article {pmid38593618, year = {2024}, author = {Chen, Y and Pei, X and Chen, L and Chen, L}, title = {A dynamic regulatory switch for phase separation of FUS protein: Zinc ions and zinc finger domain.}, journal = {Biochemical and biophysical research communications}, volume = {710}, number = {}, pages = {149862}, doi = {10.1016/j.bbrc.2024.149862}, pmid = {38593618}, issn = {1090-2104}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/metabolism ; Cysteine/genetics ; Mutation ; Phase Separation ; *RNA-Binding Protein FUS/chemistry/genetics/metabolism ; Zinc/metabolism ; Zinc Fingers ; Protein Aggregates ; }, abstract = {Zinc is an important trace element in the human body, and its homeostasis is closely related to amyotrophic lateral sclerosis (ALS). Cytoplasmic FUS proteins from patients with ALS aggregate their important pathologic markers. Liquid-liquid phase separation (LLPS) of FUS can lead to its aggregation. However, whether and how zinc homeostasis affects the aggregation of disease-associated FUS proteins in the cytoplasm remains unclear. Here, we found that zinc ion enhances LLPS and promotes the aggregation in the cytoplasm for FUS protein. In the FUS, the cysteine of the zinc finger (ZnF), recognizes and binds to zinc ions, reducing droplet mobility and enhancing protein aggregation in the cytoplasm. The mutation of FUS cysteine disrupts the dynamic regulatory switch of zinc ions and ZnF, resulting in insensitivity to zinc ions. These results suggest that the dynamic regulation of LLPS by binding with zinc ions may be a widespread mechanism and provide a new understanding of neurological diseases such as ALS and other ZnF protein-related diseases.}, } @article {pmid38593537, year = {2024}, author = {Vijayakumar, S and Schwaighofer, A and Ramer, G and Lendl, B}, title = {Multivariate curve resolution -alternating least squares augmented with partial least squares baseline correction applied to mid-IR laser spectra resolves protein denaturation by reducing rotational ambiguity.}, journal = {Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy}, volume = {315}, number = {}, pages = {124228}, doi = {10.1016/j.saa.2024.124228}, pmid = {38593537}, issn = {1873-3557}, abstract = {High spectral power density provided by advances in external cavity quantum cascade lasers (EC-QCL) have enabled increased transmission path lengths in mid-infrared (mid-IR) spectroscopy for more sensitive measurement of proteins in aqueous solutions. These extended path lengths also facilitate flow through measurements by avoiding congestion of the flow cell by protein aggregates. Despite the advantages presented by laser-based mid-IR spectroscopy of proteins, extraction of secondary structure information from spectra, especially in the presence of complex multi-component matrices with overlapping spectral features, remains an impediment that requires fine tuning of evaluation algorithms (e.g., band fitting, interpretation of second derivative spectra etc.). In this work, the use of multivariate curve resolution alternating least squares (MCR-ALS) for the analysis of a chemical de- and renaturation experiment has been demonstrated, since this technique offers the second-order advantage of extracting spectral signatures and concentration profiles even in the presence of unknown, uncalibrated constituents. Furthermore, we exhibit a partial least squares regression (PLSR) based subtraction of matrix component spectra prior to MCR-ALS as a method to obtain secondary structure information even in the absence of reference spectra. These approaches are showcased using the online reaction monitoring of the titration of β-lactoglobulin (β-LG) in water against the surfactants sodium dodecyl sulfate (SDS) and octaethylene glyol monododecyl ether (C12E8), using a commercially available laser-based IR spectrometer. Results for the automated PLSR correction plus MCR-ALS approach compare favorably to an MCR-ALS standalone approach using initial estimates as well as analysis of secondary structure using data processed with a manual baseline correction. The herein described chemometric approach suggests a way to simplify the challenge of handling complex matrices in protein structure analysis by isolating the background from the protein contributions, prior to analysis via other soft-modelling techniques. Consequently, the findings of this study indicate the suitability of online reaction monitoring through mid-IR spectroscopy combined with chemometric techniques as a potential tool in downstream quality control and process automation.}, } @article {pmid38593477, year = {2024}, author = {Lindborg, SR and Goyal, NA and Katz, J and Burford, M and Li, J and Kaspi, H and Abramov, N and Boulanger, B and Berry, JD and Nicholson, K and Mozaffar, T and Miller, R and Jenkins, L and Baloh, RH and Lewis, R and Staff, NP and Owegi, MA and Dagher, B and Blondheim-Shraga, NR and Gothelf, Y and Levy, YS and Kern, R and Aricha, R and Windebank, AJ and Bowser, R and Brown, RH and Cudkowicz, ME}, title = {Debamestrocel multimodal effects on biomarker pathways in amyotrophic lateral sclerosis are linked to clinical outcomes.}, journal = {Muscle & nerve}, volume = {69}, number = {6}, pages = {719-729}, doi = {10.1002/mus.28093}, pmid = {38593477}, issn = {1097-4598}, support = {//California Institute for Regenerative Medicine/ ; //I AM ALS/ ; //ALS Association/ ; }, mesh = {Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; *Amyotrophic Lateral Sclerosis/cerebrospinal fluid/drug therapy/diagnosis ; *Biomarkers/cerebrospinal fluid ; Double-Blind Method ; *Neurofilament Proteins/cerebrospinal fluid ; Treatment Outcome ; }, abstract = {INTRODUCTION/AIMS: Biomarkers have shown promise in amyotrophic lateral sclerosis (ALS) research, but the quest for reliable biomarkers remains active. This study evaluates the effect of debamestrocel on cerebrospinal fluid (CSF) biomarkers, an exploratory endpoint.

METHODS: A total of 196 participants randomly received debamestrocel or placebo. Seven CSF samples were to be collected from all participants. Forty-five biomarkers were analyzed in the overall study and by two subgroups characterized by the ALS Functional Rating Scale-Revised (ALSFRS-R). A prespecified model was employed to predict clinical outcomes leveraging biomarkers and disease characteristics. Causal inference was used to analyze relationships between neurofilament light chain (NfL) and ALSFRS-R.

RESULTS: We observed significant changes with debamestrocel in 64% of the biomarkers studied, spanning pathways implicated in ALS pathology (63% neuroinflammation, 50% neurodegeneration, and 89% neuroprotection). Biomarker changes with debamestrocel show biological activity in trial participants, including those with advanced ALS. CSF biomarkers were predictive of clinical outcomes in debamestrocel-treated participants (baseline NfL, baseline latency-associated peptide/transforming growth factor beta1 [LAP/TGFβ1], change galectin-1, all p < .01), with baseline NfL and LAP/TGFβ1 remaining (p < .05) when disease characteristics (p < .005) were incorporated. Change from baseline to the last measurement showed debamestrocel-driven reductions in NfL were associated with less decline in ALSFRS-R. Debamestrocel significantly reduced NfL from baseline compared with placebo (11% vs. 1.6%, p = .037).

DISCUSSION: Following debamestrocel treatment, many biomarkers showed increases (anti-inflammatory/neuroprotective) or decreases (inflammatory/neurodegenerative) suggesting a possible treatment effect. Neuroinflammatory and neuroprotective biomarkers were predictive of clinical response, suggesting a potential multimodal mechanism of action. These results offer preliminary insights that need to be confirmed.}, } @article {pmid38592845, year = {2024}, author = {Lerose, V and Ponticelli, M and Benedetto, N and Carlucci, V and Lela, L and Tzvetkov, NT and Milella, L}, title = {Withania somnifera (L.) Dunal, a Potential Source of Phytochemicals for Treating Neurodegenerative Diseases: A Systematic Review.}, journal = {Plants (Basel, Switzerland)}, volume = {13}, number = {6}, pages = {}, pmid = {38592845}, issn = {2223-7747}, support = {CUP: B34I20000320005//Project RESO - REsilienza e SOstenibilità delle filiere ortofrutticole e cerealicole per valorizzare i territori" - cod. identif. ARS01_01224 -/ ; CUP: G49J19001350004//Project SPIA-Valorization of by-products from the agro-food chain/ ; CUP: ECS00000036//Project NODES - Ecosistema dell'Innovazione "Nord Ovest Digitale e Sostenibile"/ ; }, abstract = {Withania somnifera (L.) Dunal is a medicinal plant belonging to the traditional Indian medical system, showing various therapeutic effects such as anti-cancer, anti-inflammatory, anti-microbial, anti-diabetic, and hepatoprotective activity. Of great interest is W. somnifera's potential beneficial effect against neurodegenerative diseases, since the authorized medicinal treatments can only delay disease progression and provide symptomatic relief and are not without side effects. A systematic search of PubMed and Scopus databases was performed to identify preclinical and clinical studies focusing on the applications of W. somnifera in preventing neurodegenerative diseases. Only English articles and those containing the keywords (Withania somnifera AND "neurodegenerative diseases", "neuroprotective effects", "Huntington", "Parkinson", "Alzheimer", "Amyotrophic Lateral Sclerosis", "neurological disorders") in the title or abstract were considered. Reviews, editorials, letters, meta-analyses, conference papers, short surveys, and book chapters were not considered. Selected articles were grouped by pathologies and summarized, considering the mechanism of action. The quality assessment and the risk of bias were performed using the Cochrane Handbook for Systematic Reviews of Interventions checklist. This review uses a systematic approach to summarize the results from 60 investigations to highlight the potential role of W. somnifera and its specialized metabolites in treating or preventing neurodegenerative diseases.}, } @article {pmid38591790, year = {2024}, author = {Lochner, RH and Arumanayagam, AS and Powell, SZ and Masdeu, JC and Pascual, B and Cykowski, MD}, title = {Anterior insula is more vulnerable than posterior insula to TDP-43 pathology in common dementias and ALS.}, journal = {Journal of neuropathology and experimental neurology}, volume = {83}, number = {5}, pages = {307-317}, pmid = {38591790}, issn = {1554-6578}, support = {RF1 NS118584/NS/NINDS NIH HHS/United States ; RF1NS118584/NS/NINDS NIH HHS/United States ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/complications/pathology ; *Dementia ; DNA-Binding Proteins ; Neurons/pathology ; *TDP-43 Proteinopathies/pathology ; }, abstract = {Based on the anatomic proximity, connectivity, and functional similarities between the anterior insula and amygdala, we tested the hypothesis that the anterior insula is an important focus in the progression of TDP-43 pathology in LATE-NC. Blinded to clinical and neuropathologic data, phospho-TDP (pTDP) inclusion pathology was assessed in paired anterior and posterior insula samples in 105 autopsied patients with Alzheimer disease, Lewy body disease, LATE-NC and hippocampal sclerosis (HS), amyotrophic lateral sclerosis (ALS), and other conditions. Insular pTDP pathology was present in 34.3% of the study cohort, most commonly as neuronal inclusions and/or short neurites in lamina II, and less commonly as subpial processes resembling those described in the amygdala region. Among positive samples, pTDP pathology was limited to the anterior insula (41.7%), or occurred in both anterior and posterior insula (58.3%); inclusion density was greater in anterior insula across all diseases (p < .001). pTDP pathology occurred in 46.7% of ALS samples, typically without a widespread TDP-43 proteinopathy. In LATE-NC, it was seen in 30.4% of samples (mostly LATE-NC stages 2 and 3), often co-occurring with basal forebrain pathology and comorbid HS, suggesting this is an important step in the evolution of this pathology beyond the medial temporal lobe.}, } @article {pmid38591728, year = {2024}, author = {Koysuren, A and Temucin, CM}, title = {Concentric needle jitter analysis of the genioglossus muscle in patients with motor neuron disease.}, journal = {Neurological research}, volume = {46}, number = {6}, pages = {578-582}, doi = {10.1080/01616412.2024.2339096}, pmid = {38591728}, issn = {1743-1328}, mesh = {Humans ; Male ; Female ; Middle Aged ; *Electromyography/methods ; *Motor Neuron Disease/physiopathology/diagnosis ; Aged ; *Muscle, Skeletal/physiopathology ; Adult ; Needles ; Tongue/physiopathology ; }, abstract = {OBJECTIVES: Difficulty relaxing the genioglossus muscle makes the evaluation of spontaneous activity problematic in patients with motor neuron disease (MND). We performed jitter analysis using conventional disposable concentric needle electrodes (CNEs) of the voluntarily activated genioglossus muscle in patients with and without MND to detect the denervation-reinnervation process.

METHODS: CNE jitter analysis was performed at the genioglossus muscle in 21 MND(+) patients and 22 MND(-) subjects. The jitter analysis was considered abnormal if the jitter values exceeded these limits for the mean consecutive difference (MCD) or the individual MCD in more than 10% of readings.

RESULTS: Seventeen MND(+) patients (81%) had at least three abnormal individual jitter values whereas denervation findings were obtained in eleven of them during the needle electromyographic examination at genioglossus muscle. None of the MND(-) subjects showed CNE jitter abnormality.

CONCLUSION: CNE jitter analysis of genioglossus muscle may provide an useful information that may be suggestive of a diagnosis of MND/ALS.}, } @article {pmid38591201, year = {2024}, author = {Roy, T and Padhi, S and Mazumder, R and Majee, C and Das, S and Monika, and Mishra, R and Kapoor, B}, title = {Alleviating Neurodegenerative Diseases Associated with Mitochondrial Defects by Therapeutic Biomolecules.}, journal = {Current topics in medicinal chemistry}, volume = {24}, number = {16}, pages = {1377-1407}, pmid = {38591201}, issn = {1873-4294}, mesh = {Humans ; *Neurodegenerative Diseases/drug therapy/metabolism ; *Mitochondria/metabolism/drug effects ; *Antioxidants/pharmacology/chemistry ; Reactive Oxygen Species/metabolism ; Animals ; }, abstract = {Neurodegenerative diseases are emerging as a global health concern in the current scenario, and their association with mitochondrial defects has been a potential area of research. Mitochondria, one of the essential organelles of the cell, serve as the cell's powerhouse, producing energy and ensuring cellular health. Neurodegenerative diseases such as Alzheimer's, Parkinson's, Huntington's, amyotrophic lateral sclerosis, and Pelizaeus-Merzbacher disease have been found to be primarily triggered by mitochondrial malfunction. One of the key byproducts of mitochondrial respiration, reactive oxygen species, also contributes significantly to mitochondrial DNA mutations that eventually cause mitochondrial breakdown. This review paper comprehensively examines the potential of therapeutic biomolecules, specifically mitochondria-specific antioxidants, in mitigating the impact of mitochondrial defects on neurodegenerative diseases. It provides a detailed analysis of the mechanisms involved in mitochondrial dysfunction, the potential therapeutic targets of these biomolecules, and their structureactivity relationship information are also discussed in this review. Various research articles and publications were used extensively in compiling the data, and the structures of biomolecules were prepared using software such as ChemDraw and ChemSketch. Crucial elements triggering mitochondrial abnormalities were identified and a tabular compilation of bioactive antioxidant compounds along with their therapeutic targets, was presented. Mitochondria-specific antioxidant therapy is an innovative and promising strategy for the management of neurodegenerative diseases associated with mitochondrial defects. This review provides a thorough summary of the current state of research and promising avenues of research and development in this field, emphasizing the importance of further investigations and clinical trials to elucidate their therapeutic benefits.}, } @article {pmid38591193, year = {2024}, author = {Rhodes, E and Alfa, S and Jin, HA and Massimo, L and Elman, L and Amado, D and Baer, M and Quinn, C and McMillan, CT}, title = {Cognitive reserve in ALS: the role of occupational skills and requirements.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {25}, number = {5-6}, pages = {486-495}, pmid = {38591193}, issn = {2167-9223}, support = {K23 AG083124/AG/NIA NIH HHS/United States ; P01 AG066597/AG/NIA NIH HHS/United States ; K01 AG061277/AG/NIA NIH HHS/United States ; K08 NS114106/NS/NINDS NIH HHS/United States ; P30 AG073105/AG/NIA NIH HHS/United States ; P30 AG072979/AG/NIA NIH HHS/United States ; R01 AG054519/AG/NIA NIH HHS/United States ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/psychology/physiopathology/complications/diagnosis ; *Cognitive Reserve/physiology ; Male ; Female ; Middle Aged ; Aged ; Neuropsychological Tests ; Cognitive Dysfunction/etiology/physiopathology/diagnosis/psychology ; Adult ; Occupations ; }, abstract = {OBJECTIVE: Amyotrophic Lateral Sclerosis (ALS) is a heterogeneous neurodegenerative condition featuring variable degrees of motor and cognitive impairment. We assessed the impact of specific, empirically derived occupational skills and requirements on cognitive and motor functioning in ALS.

METHODS: Individuals with ALS (n = 150) were recruited from the University of Pennsylvania's Comprehensive ALS Clinic. The Edinburgh Cognitive and Behavioral ALS Screen (ECAS) measured cognition, and the Penn Upper Motor Neuron (PUMNS) and ALS Functional Rating Scales (ALSFRS-R) measured motor symptoms. We derived 17 factors representing distinct occupational skills and requirements from the Occupational Information Network (O*NET), which were related to cognitive and motor scores using multiple linear regression.

RESULTS: Occupational roles involving greater reasoning ability (β = 2.12, p < .05), social ability (β = 1.73, p < .05), analytic skills, (β = 3.12, p < .01) and humanities knowledge (β = 1.83, p<.01) were associated with better performance on the ECAS, while jobs involving more exposure to environmental hazards (β=-2.57, p < .01) and technical skills (β=-2.16, p<.01) were associated with lower ECAS scores. Jobs requiring more precision skills (β = 1.91, p < .05) were associated with greater motor dysfunction on the PUMNS.

CONCLUSIONS: Occupational histories involving more cognitively complex skills and activities were related to preserved cognitive functioning in ALS consistent with the cognitive reserve hypothesis, while jobs with greater exposure to environmental hazards and technical demands were linked to poorer cognitive functioning. Jobs involving more repetitive movements were associated with worse motor functioning, possibly due to overuse. Occupational history provides insight into protective and risk factors for variable degrees of cognitive and motor dysfunction in ALS.}, } @article {pmid38591179, year = {2024}, author = {Talbott, EO and Malek, AM and Arena, VC and Wu, F and Steffes, K and Sharma, RK and Buchanich, J and Rager, JR and Bear, T and Hoffman, CA and Lacomis, D and Donnelly, C and Mauna, J and Vena, JE}, title = {Case-control study of environmental toxins and risk of amyotrophic lateral sclerosis involving the national ALS registry.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {25}, number = {5-6}, pages = {533-542}, doi = {10.1080/21678421.2024.2336108}, pmid = {38591179}, issn = {2167-9223}, support = {R01 TS000272/TS/ATSDR CDC HHS/United States ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/epidemiology/blood/chemically induced ; Male ; Female ; Middle Aged ; Case-Control Studies ; *Registries ; Aged ; Risk Factors ; *Environmental Exposure/adverse effects/statistics & numerical data ; Occupational Exposure/adverse effects/statistics & numerical data ; Pesticides/blood/adverse effects ; United States/epidemiology ; }, abstract = {OBJECTIVE: Neurotoxic chemicals are suggested in the etiology of amyotrophic lateral sclerosis (ALS). We examined the association of environmental and occupational risk factors including persistent organochlorine pesticides (OCPs) and ALS risk among cases from the Centers for Disease Control and Prevention National ALS Registry and age, sex, and county-matched controls.

METHODS: Participants completed a risk factor survey and provided a blood sample for OCP measurement. ALS cases were confirmed through the Registry. Conditional logistic regression assessed associations between ALS and risk factors including OCP levels.

RESULTS: 243 matched case-control pairs (61.7% male, mean [SD] age = 62.9 [10.1]) were included. Fifteen of the 29 OCPs examined had sufficient detectable levels for analysis. Modest correlations of self-reported years of exposure to residential pesticide mixtures and OCP serum levels were found (p<.001). Moreover, occupational exposure to lead including soldering and welding with lead/metal dust and use of lead paint/gasoline were significantly related to ALS risk (OR = 1.77, 95% CI: 1.11-2.83). Avocational gardening was a significant risk factor for ALS (OR = 1.57, 95% CI: 1.04-2.37). ALS risk increased for each 10 ng/g of α-Endosulfan (OR = 1.42, 95% CI: 1.14-1.77) and oxychlordane (OR = 1.24, 95% CI: 1.01-1.53). Heptachlor (detectable vs. nondetectable) was also associated with ALS risk (OR = 3.57, 95% CI: 1.50-8.52).

CONCLUSION: This national case-control study revealed both survey and serum levels of OCPs as risk factors for ALS. Despite the United States banning many OCPs in the 1970s and 1980s, their use abroad and long half-lives continue to exert possible neurotoxic health effects.}, } @article {pmid38590640, year = {2024}, author = {Scaricamazza, S and Nesci, V and Salvatori, I and Fenili, G and Rosina, M and Gloriani, M and Paronetto, MP and Madaro, L and Ferri, A and Valle, C}, title = {Endurance exercise has a negative impact on the onset of SOD1-G93A ALS in female mice and affects the entire skeletal muscle-motor neuron axis.}, journal = {Frontiers in pharmacology}, volume = {15}, number = {}, pages = {1360099}, pmid = {38590640}, issn = {1663-9812}, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a fatal neuromuscular disease characterized by the degeneration of motor neurons that leads to muscle wasting and atrophy. Epidemiological and experimental evidence suggests a causal relationship between ALS and physical activity (PA). However, the impact of PA on motor neuron loss and sarcopenia is still debated, probably because of the heterogeneity and intensities of the proposed exercises. With this study, we aimed to clarify the effect of intense endurance exercise on the onset and progression of ALS in the SOD1-G93A mouse model.

METHODS: We randomly selected four groups of twelve 35-day-old female mice. SOD1-G93A and WT mice underwent intense endurance training on a motorized treadmill for 8 weeks, 5 days a week. During the training, we measured muscle strength, weight, and motor skills and compared them with the corresponding sedentary groups to define the disease onset. At the end of the eighth week, we analyzed the skeletal muscle-motor neuron axis by histological and molecular techniques.

RESULTS: Intense endurance exercise anticipates the onset of the disease by 1 week (age of the onset: trained SOD1-G93A = 63.17 ± 2.25 days old; sedentary SOD1-G93A = 70.75 ± 2.45 days old). In SOD1-G93A mice, intense endurance exercise hastens the muscular switch to a more oxidative phenotype and worsens the denervation process by dismantling neuromuscular junctions in the tibialis anterior, enhancing the Wallerian degeneration in the sciatic nerve, and promoting motor neuron loss in the spinal cord. The training exacerbates neuroinflammation, causing immune cell infiltration in the sciatic nerve and a faster activation of astrocytes and microglia in the spinal cord.

CONCLUSION: Intense endurance exercise, acting on skeletal muscles, worsens the pathological hallmarks of ALS, such as denervation and neuroinflammation, brings the onset forward, and accelerates the progression of the disease. Our findings show the potentiality of skeletal muscle as a target for both prognostic and therapeutic strategies; the preservation of skeletal muscle health by specific intervention could counteract the dying-back process and protect motor neurons from death. The physiological characteristics and accessibility of skeletal muscle further enhance its appeal as a therapeutic target.}, } @article {pmid38589279, year = {2024}, author = {Iwasaki, Y}, title = {[Neuropathology of the Neurodegenerative Diseases].}, journal = {Brain and nerve = Shinkei kenkyu no shinpo}, volume = {76}, number = {4}, pages = {343-351}, doi = {10.11477/mf.1416202611}, pmid = {38589279}, issn = {1881-6096}, mesh = {Humans ; tau Proteins/metabolism ; *Amyotrophic Lateral Sclerosis/pathology ; *Tauopathies/metabolism/pathology ; *Pick Disease of the Brain/metabolism/pathology ; *Frontotemporal Dementia ; *Frontotemporal Lobar Degeneration ; *Multiple System Atrophy ; DNA-Binding Proteins/metabolism ; }, abstract = {A definite diagnosis of neurodegenerative diseases is required for neuropathological examination during an autopsy. Each neurodegenerative disease has specific vulnerable regions and affected systems (system degeneration), and is typified by an accumulation of abnormal protein with the formation of characteristic morphological aggregates in the nerve and glial cells, called proteinopathy. The most common neurodegenerative diseases are tauopathy, such as progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and Pick's disease (PiD); α-synucleinopathy, including multiple system atrophy (MSA); and TAR DNA-binding protein of 43 kDa (TDP-43) proteinopathy, including amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). PSP and CBD show characteristic tau-positive astrocytic inclusions known as tufted astrocytes and astrocytic plaques, respectively. PiD shows tau-positive neuronal inclusions termed Pick bodies. MSA is characterized by α-synuclein-positive oligodendroglial inclusions, called glial cytoplasmic inclusions. ALS- and FTLD-TDP show TDP-43-positive neuronal inclusions, such as skein-like and round inclusions. Huntington's disease shows polyglutamine-positive neuronal inclusions, and Creutzfeldt-Jakob disease shows diffuse deposition of granular prions in the neuropil. The atypical proteins in these diseases have abnormal conformational properties. A comprehensive comparison of the clinical findings and neuropathological observations, including neuroanatomy and images acquired during life, is important to improve the sensitivity of clinical diagnosis.}, } @article {pmid38588013, year = {2024}, author = {El Hajj, R and Al Sagheer, T and Ballout, N}, title = {Optogenetics in chronic neurodegenerative diseases, controlling the brain with light: A systematic review.}, journal = {Journal of neuroscience research}, volume = {102}, number = {4}, pages = {e25321}, doi = {10.1002/jnr.25321}, pmid = {38588013}, issn = {1097-4547}, mesh = {*Optogenetics/methods ; Animals ; *Neurodegenerative Diseases/therapy/genetics ; Humans ; *Brain/metabolism ; Disease Models, Animal ; Neurons/physiology/metabolism ; Deep Brain Stimulation/methods ; }, abstract = {Neurodegenerative diseases are progressive disorders characterized by synaptic loss and neuronal death. Optogenetics combines optical and genetic methods to control the activity of specific cell types. The efficacy of this approach in neurodegenerative diseases has been investigated in many reviews, however, none of them tackled it systematically. Our study aimed to review systematically the findings of optogenetics and its potential applications in animal models of chronic neurodegenerative diseases and compare it with deep brain stimulation and designer receptors exclusively activated by designer drugs techniques. The search strategy was performed based on the PRISMA guidelines and the risk of bias was assessed following the Systematic Review Centre for Laboratory Animal Experimentation tool. A total of 247 articles were found, of which 53 were suitable for the qualitative analysis. Our data revealed that optogenetic manipulation of distinct neurons in the brain is efficient in rescuing memory impairment, alleviating neuroinflammation, and reducing plaque pathology in Alzheimer's disease. Similarly, this technique shows an advanced understanding of the contribution of various neurons involved in the basal ganglia pathways with Parkinson's disease motor symptoms and pathology. However, the optogenetic application using animal models of Huntington's disease, multiple sclerosis, and amyotrophic lateral sclerosis was limited. Optogenetics is a promising technique that enhanced our knowledge in the research of neurodegenerative diseases and addressed potential therapeutic solutions for managing these diseases' symptoms and delaying their progression. Nevertheless, advanced investigations should be considered to improve optogenetic tools' efficacy and safety to pave the way for their translatability to the clinic.}, } @article {pmid38586597, year = {2024}, author = {Zhang, T and Bao, L and Chen, H}, title = {Review of Phenotypic Heterogeneity of Neuronal Intranuclear Inclusion Disease and NOTCH2NLC-Related GGC Repeat Expansion Disorders.}, journal = {Neurology. Genetics}, volume = {10}, number = {2}, pages = {e200132}, pmid = {38586597}, issn = {2376-7839}, abstract = {Neuronal intranuclear inclusion disease (NIID) is an underdiagnosed neurodegenerative disorder caused by pathogenic GGC expansions in NOTCH2NLC. However, an increasing number of reports of NOTCH2NLC GGC expansions in patients with Alzheimer disease, essential tremor, Parkinson disease, amyotrophic lateral sclerosis, and oculopharyngodistal myopathy have led to the proposal of a new concept known as NOTCH2NLC-related GGC repeat expansion disorders (NREDs). The majority of studies have mainly focused on screening for NOTCH2NLC GGC repeat variation in populations previously diagnosed with the associated disease, subsequently presenting it as a novel causative gene for the condition. These studies appear to be clinically relevant but do have their limitations because they may incorrectly regard the lack of MRI abnormalities as an exclusion criterion for NIID or overlook concomitant clinical presentations not typically observed in the associated diseases. Besides, in many instances within these reports, patients lack pathologic evidence or undergo long-term follow-up to conclusively rule out NIID. In this review, we will systematically review the research on NOTCH2NLC 5' untranslated region GGC repeat expansions and their association with related neurologic disorders, explaining the limitations of the relevant reports. Furthermore, we will integrate subsequent studies to further demonstrate that these patients actually experienced distinct clinical phenotypes of NIID.}, } @article {pmid38585945, year = {2024}, author = {Haider, R and Shipley, B and Surewicz, K and Hinczewski, M and Surewicz, WK}, title = {Pathological C-terminal phosphomimetic substitutions alter the mechanism of liquid-liquid phase separation of TDP-43 low complexity domain.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {38585945}, issn = {2692-8205}, support = {RF1 AG061797/AG/NIA NIH HHS/United States ; T32 GM007250/GM/NIGMS NIH HHS/United States ; T32 NS077888/NS/NINDS NIH HHS/United States ; }, abstract = {C-terminally phosphorylated TAR DNA-binding protein of 43 kDa (TDP-43) marks the proteinaceous inclusions that characterize a number of age-related neurodegenerative diseases, including amyotrophic lateral sclerosis, frontotemporal lobar degeneration and Alzheimer's disease. TDP-43 phosphorylation at S403/S404, and especially at S409/S410, is in fact accepted as a biomarker of proteinopathy. These residues are located within the low complexity domain (LCD), which also drives the protein's liquid-liquid phase separation (LLPS). The impact of phosphorylation at these LCD sites on phase separation of the protein is a topic of great interest, as these post-translational modifications and LLPS are both implicated in proteinopathies. Here, we employed a combination of experimental and simulation-based approaches to explore this question on a phosphomimetic model of the TDP-43 LCD. Our turbidity and fluorescence microscopy data show that Ser-to-Asp substitutions at residues S403, S404, S409 and S410 alter the LLPS behavior of TDP-43 LCD. In particular, in contrast to the unmodified protein, the phosphomimetic variants display a biphasic dependence on salt concentration. Through coarse-grained modeling, we find that this biphasic salt dependence is derived from an altered mechanism of phase separation, in which LLPS-driving short-range intermolecular hydrophobic interactions are modulated by long-range attractive electrostatic interactions. Overall, this in vitro and in silico study provides a physiochemical foundation for understanding the impact of pathologically-relevant C-terminal phosphorylation on the LLPS of the TDP-43 in a more complex cellular environment.}, } @article {pmid38585915, year = {2024}, author = {Martin, EJ and Santacruz, C and Mitevska, A and Jones, IE and Krishnan, G and Gao, FB and Finan, JD and Kiskinis, E}, title = {Traumatic injury causes selective degeneration and TDP-43 mislocalization in human iPSC-derived C9orf72-associated ALS/FTD motor neurons.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {38585915}, issn = {2692-8205}, support = {RF1 NS101986/NS/NINDS NIH HHS/United States ; R01 NS134166/NS/NINDS NIH HHS/United States ; R37 NS057553/NS/NINDS NIH HHS/United States ; R01 NS113935/NS/NINDS NIH HHS/United States ; R01 NS104219/NS/NINDS NIH HHS/United States ; }, abstract = {A hexanucleotide repeat expansion (HRE) in C9orf72 is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). However, patients with the HRE exhibit a wide disparity in clinical presentation and age of symptom onset suggesting an interplay between genetic background and environmental stressors. Neurotrauma as a result of traumatic brain or spinal cord injury has been shown to increase the risk of ALS/FTD in epidemiological studies. Here, we combine patient-specific induced pluripotent stem cells (iPSCs) with a custom-built device to deliver biofidelic stretch trauma to C9orf72 patient and isogenic control motor neurons (MNs) in vitro. We find that mutant but not control MNs exhibit selective degeneration after a single incident of severe trauma, which can be partially rescued by pretreatment with a C9orf72 antisense oligonucleotide. A single incident of mild trauma does not cause degeneration but leads to cytoplasmic accumulation of TDP-43 in C9orf72 MNs. This mislocalization, which only occurs briefly in isogenic controls, is eventually restored in C9orf72 MNs after 6 days. Lastly, repeated mild trauma ablates the ability of patient MNs to recover. These findings highlight alterations in TDP-43 dynamics in C9orf72 ALS/FTD patient MNs following traumatic injury and demonstrate that neurotrauma compounds neuropathology in C9orf72 ALS/FTD. More broadly, our work establishes an in vitro platform that can be used to interrogate the mechanistic interactions between ALS/FTD and neurotrauma.}, } @article {pmid38585910, year = {2024}, author = {Jin, W and Boss, J and Bakulski, KM and Goutman, SA and Feldman, EL and Fritsche, LG and Mukherjee, B}, title = {Improving prediction models of amyotrophic lateral sclerosis (ALS) using polygenic, pre-existing conditions, and survey-based risk scores in the UK Biobank.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, pmid = {38585910}, support = {R01TS000344/ACL/ACL HHS/United States ; K23 ES027221/ES/NIEHS NIH HHS/United States ; R01 ES030049/ES/NIEHS NIH HHS/United States ; R01 NS127188/NS/NINDS NIH HHS/United States ; R01 TS000344/TS/ATSDR CDC HHS/United States ; }, abstract = {BACKGROUND AND OBJECTIVES: Amyotrophic lateral sclerosis (ALS) causes profound impairments in neurological function and a cure for this devastating disease remains elusive. Early detection and risk stratification are crucial for timely intervention and improving patient outcomes. This study aimed to identify predisposing genetic, phenotypic, and exposure-related factors for Amyotrophic lateral sclerosis using multi-modal data and assess their joint predictive potential.

METHODS: Utilizing data from the UK Biobank, we analyzed an unrelated set of 292 ALS cases and 408,831 controls of European descent. Two polygenic risk scores (PRS) are constructed: "GWAS Hits PRS" and "PRS-CS," reflecting oligogenic and polygenic ALS risk profiles, respectively. Time-restricted phenome-wide association studies (PheWAS) were performed to identify pre-existing conditions increasing ALS risk, integrated into phenotypic risk scores (PheRS). A poly-exposure score ("PXS") captures the influence of environmental exposures measured through survey questionnaires. We evaluate the performance of these scores for predicting ALS incidence and stratifying risk, adjusting for baseline demographic covariates.

RESULTS: Both PRSs modestly predicted ALS diagnosis, but with increased predictive power when combined (covariate-adjusted receiver operating characteristic [AAUC] = 0.584 [0.525, 0.639]). PheRS incorporated diagnoses 1 year before ALS onset (PheRS1) modestly discriminated cases from controls (AAUC = 0.515 [0.472, 0.564]). The "PXS" did not significantly predict ALS. However, a model incorporating PRSs and PheRS1 improved prediction of ALS (AAUC = 0.604 [0.547, 0.667]), outperforming a model combining all risk scores. This combined risk score identified the top 10% of risk score distribution with a 4-fold higher ALS risk (95% CI: [2.04, 7.73]) versus those in the 40%-60% range.

DISCUSSIONS: By leveraging UK Biobank data, our study uncovers predisposing ALS factors, highlighting the improved effectiveness of multi-factorial prediction models to identify individuals at highest risk for ALS.}, } @article {pmid38585891, year = {2024}, author = {Antonucci, S and Caron, G and Dikwella, N and Krishnamurty, SS and Harster, A and Zarrin, H and Tahanis, A and Heuvel, FO and Danner, SM and Ludolph, AC and Grycz, K and Bączyk, M and Zytnicki, D and Roselli, F}, title = {Spinal motoneuron excitability is homeostatically-regulated through β-adrenergic neuromodulation in wild-type and presymptomatic SOD1 mice.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {38585891}, issn = {2692-8205}, support = {R01 NS110953/NS/NINDS NIH HHS/United States ; R01 NS112304/NS/NINDS NIH HHS/United States ; R01 NS115900/NS/NINDS NIH HHS/United States ; }, abstract = {Homeostatic feedback loops are essential to stabilize the activity of neurons and neuronal networks. It has been hypothesized that, in the context of Amyotrophic Lateral Sclerosis (ALS), an excessive gain in feedback loops might hyper- or hypo-excite motoneurons (MNs) and contribute to the pathogenesis. Here, we investigated how the neuromodulation of MN intrinsic properties is homeostatically controlled in presymptomatic adult SOD1(G93A) mice and in the age-matched control WT mice. First, we determined that β2 and β3- adrenergic receptors, which are Gs-coupled receptors and subject to tight and robust feedback loops, are specifically expressed in spinal MNs of both SOD1 and WT mice at P45. We then demonstrated that these receptors elicit a so-far overlooked neuromodulation of the firing and excitability properties of MNs. These electrical properties are homeostatically regulated following receptor engagement, which triggers ion channel transcriptional changes and downregulates those receptors. These homeostatic feedbacks are not dysregulated in presymptomatic SOD1 mice, and they set the MN excitability upon β-adrenergic neuromodulation.}, } @article {pmid38585774, year = {2024}, author = {Yu, M and Xu, J and Dutta, R and Trapp, B and Pieper, AA and Cheng, F}, title = {Network medicine informed multi-omics integration identifies drug targets and repurposable medicines for Amyotrophic Lateral Sclerosis.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {38585774}, issn = {2692-8205}, support = {R21 AG083003/AG/NIA NIH HHS/United States ; R01 AG082118/AG/NIA NIH HHS/United States ; R56 AG074001/AG/NIA NIH HHS/United States ; RF1 AG082211/AG/NIA NIH HHS/United States ; R01 AG084250/AG/NIA NIH HHS/United States ; RF1 NS133812/NS/NINDS NIH HHS/United States ; U01 AG073323/AG/NIA NIH HHS/United States ; R01 AG066707/AG/NIA NIH HHS/United States ; R01 AG076448/AG/NIA NIH HHS/United States ; }, abstract = {Amyotrophic Lateral Sclerosis (ALS) is a devastating, immensely complex neurodegenerative disease by lack of effective treatments. To date, the challenge to establishing effective treatment for ALS remains formidable, partly due to inadequate translation of existing human genetic findings into actionable ALS-specific pathobiology for subsequent therapeutic development. This study evaluates the feasibility of network medicine methodology via integrating human brain-specific multi-omics data to prioritize drug targets and repurposable treatments for ALS. Using human brain-specific genome-wide quantitative trait loci (x-QTLs) under a network-based deep learning framework, we identified 105 putative ALS-associated genes enriched in various known ALS pathobiological pathways, including regulation of T cell activation, monocyte differentiation, and lymphocyte proliferation. Specifically, we leveraged non-coding ALS loci effects from genome-wide associated studies (GWAS) on brain-specific expression quantitative trait loci (QTL) (eQTL), protein QTLs (pQTL), splicing QTL (sQTL), methylation QTL (meQTL), and histone acetylation QTL (haQTL). Applying network proximity analysis of predicted ALS-associated gene-coding targets and existing drug-target networks under the human protein-protein interactome (PPI) model, we identified a set of potential repurposable drugs (including Diazoxide, Gefitinib, Paliperidone, and Dimethyltryptamine) for ALS. Subsequent validation established preclinical and clinical evidence for top-prioritized repurposable drugs. In summary, we presented a network-based multi-omics framework to identify potential drug targets and repurposable treatments for ALS and other neurodegenerative disease if broadly applied.}, } @article {pmid38585725, year = {2024}, author = {Sinha, IR and Sandal, PS and Burns, GD and Mallika, AP and Irwin, KE and Cruz, ALF and Wang, V and Rodríguez, JL and Wong, PC and Ling, JP}, title = {Large-scale RNA-seq mining reveals ciclopirox triggers TDP-43 cryptic exons.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {38585725}, issn = {2692-8205}, support = {R01 NS095969/NS/NINDS NIH HHS/United States ; R33 NS115161/NS/NINDS NIH HHS/United States ; U01 FD008129/FD/FDA HHS/United States ; UH3 NS115608/NS/NINDS NIH HHS/United States ; }, abstract = {Nuclear clearance and cytoplasmic aggregation of TDP-43 in neurons, initially identified in ALS-FTD, are hallmark pathological features observed across a spectrum of neurodegenerative diseases. We previously found that TDP-43 loss-of-function leads to the transcriptome-wide inclusion of deleterious cryptic exons in brains and biofluids post-mortem as well as during the presymptomatic stage of ALS-FTD, but upstream mechanisms that lead to TDP-43 dysregulation remain unclear. Here, we developed a web-based resource (SnapMine) to determine the levels of TDP-43 cryptic exon inclusion across hundreds of thousands of publicly available RNA sequencing datasets. We established cryptic exon inclusion across a variety of human cells and tissues to provide ground truth references for future studies on TDP-43 dysregulation. We then explored studies that were entirely unrelated to TDP-43 or neurodegeneration and found that ciclopirox olamine (CPX), an FDA-approved antifungal, can trigger the inclusion of TDP-43-associated cryptic exons in a variety of mouse and human primary cells. CPX induction of cryptic exon occurs via heavy metal toxicity and oxidative stress, suggesting that similar vulnerabilities could play a role in neurodegeneration. Our work demonstrates how diverse datasets can be linked through common biological features and underscores that public archives of sequencing data represent a vastly underutilized resource with tremendous potential for uncovering novel insights into complex biological mechanisms and diseases.}, } @article {pmid38585670, year = {2024}, author = {Cipriano, L and Minino, R and Liparoti, M and Polverino, A and Romano, A and Bonavita, S and Pirozzi, MA and Quarantelli, M and Jirsa, V and Sorrentino, G and Sorrentino, P and Troisi Lopez, E}, title = {Flexibility of brain dynamics is increased and predicts clinical impairment in relapsing-remitting but not in secondary progressive multiple sclerosis.}, journal = {Brain communications}, volume = {6}, number = {2}, pages = {fcae112}, pmid = {38585670}, issn = {2632-1297}, abstract = {Large-scale brain activity has long been investigated under the erroneous assumption of stationarity. Nowadays, we know that resting-state functional connectivity is characterized by aperiodic, scale-free bursts of activity (i.e. neuronal avalanches) that intermittently recruit different brain regions. These different patterns of activity represent a measure of brain flexibility, whose reduction has been found to predict clinical impairment in multiple neurodegenerative diseases such as Parkinson's disease, amyotrophic lateral sclerosis and Alzheimer's disease. Brain flexibility has been recently found increased in multiple sclerosis, but its relationship with clinical disability remains elusive. Also, potential differences in brain dynamics according to the multiple sclerosis clinical phenotypes remain unexplored so far. We performed a brain dynamics study quantifying brain flexibility utilizing the 'functional repertoire' (i.e. the number of configurations of active brain areas) through source reconstruction of magnetoencephalography signals in a cohort of 25 multiple sclerosis patients (10 relapsing-remitting multiple sclerosis and 15 secondary progressive multiple sclerosis) and 25 healthy controls. Multiple sclerosis patients showed a greater number of unique reconfigurations at fast time scales as compared with healthy controls. This difference was mainly driven by the relapsing-remitting multiple sclerosis phenotype, whereas no significant differences in brain dynamics were found between secondary progressive multiple sclerosis and healthy controls. Brain flexibility also showed a different predictive power on clinical disability according to the multiple sclerosis type. For the first time, we investigated brain dynamics in multiple sclerosis patients through high temporal resolution techniques, unveiling differences in brain flexibility according to the multiple sclerosis phenotype and its relationship with clinical disability.}, } @article {pmid38585669, year = {2024}, author = {Novy, C and Busk, ØL and Tysnes, OB and Landa, SS and Aanjesen, TN and Alstadhaug, KB and Bjerknes, TL and Bjørnå, IK and Bråthen, G and Dahl, E and Demic, N and Fahlström, M and Flemmen, HØ and Hallerstig, E and HogenEsch, I and Kampman, MT and Kleveland, G and Kvernmo, HB and Ljøstad, U and Maniaol, A and Morsund, AH and Nakken, O and Olsen, CG and Schlüter, K and Utvik, MS and Yaseen, R and Holla, ØL and Holmøy, T and Høyer, H}, title = {Repeat expansions in AR, ATXN1, ATXN2 and HTT in Norwegian patients diagnosed with amyotrophic lateral sclerosis.}, journal = {Brain communications}, volume = {6}, number = {2}, pages = {fcae087}, pmid = {38585669}, issn = {2632-1297}, abstract = {Genetic repeat expansions cause neuronal degeneration in amyotrophic lateral sclerosis as well as other neurodegenerative disorders such as spinocerebellar ataxia, Huntington's disease and Kennedy's disease. Repeat expansions in the same gene can cause multiple clinical phenotypes. We aimed to characterize repeat expansions in a Norwegian amyotrophic lateral sclerosis cohort. Norwegian amyotrophic lateral sclerosis patients (n = 414) and neurologically healthy controls adjusted for age and gender (n = 713) were investigated for repeat expansions in AR, ATXN1, ATXN2 and HTT using short read exome sequencing and the ExpansionHunter software. Five amyotrophic lateral sclerosis patients (1.2%) and two controls (0.3%) carried ≥36 repeats in HTT (P = 0.032), and seven amyotrophic lateral sclerosis patients (1.7%) and three controls (0.4%) carried ≥29 repeats in ATXN2 (P = 0.038). One male diagnosed with amyotrophic lateral sclerosis carried a pathogenic repeat expansion in AR, and his diagnosis was revised to Kennedy's disease. In ATXN1, 50 amyotrophic lateral sclerosis patients (12.1%) and 96 controls (13.5%) carried ≥33 repeats (P = 0.753). None of the patients with repeat expansions in ATXN2 or HTT had signs of Huntington's disease or spinocerebellar ataxia type 2, based on a re-evaluation of medical records. The diagnosis of amyotrophic lateral sclerosis was confirmed in all patients, with the exception of one patient who had primary lateral sclerosis. Our findings indicate that repeat expansions in HTT and ATXN2 are associated with increased likelihood of developing amyotrophic lateral sclerosis. Further studies are required to investigate the potential relationship between HTT repeat expansions and amyotrophic lateral sclerosis.}, } @article {pmid38585660, year = {2024}, author = {Zhang, H and Chen, C and Zhang, EE and Huang, X}, title = {TDP-43 deficiency in suprachiasmatic nucleus perturbs rhythmicity of neuroactivity in prefrontal cortex.}, journal = {iScience}, volume = {27}, number = {4}, pages = {109522}, pmid = {38585660}, issn = {2589-0042}, abstract = {Individuals within the amyotrophic lateral sclerosis and frontotemporal dementia disease spectrum (ALS/FTD) often experience disruptive mental behaviors and sleep-wake disturbances. The hallmark of ALS/FTD is the pathological involvement of TAR DNA-binding protein 43 (TDP-43). Understanding the role of TDP-43 in the circadian clock holds promise for addressing these behavioral abnormalities. In this study, we unveil TDP-43 as a pivotal regulator of the circadian clock. TDP-43 knockdown induces intracellular arrhythmicity, disrupts transcriptional activation regulation, and diminishes clock genes expression. Moreover, our experiments in adult mouse reveal that TDP-43 knockdown, specifically within the suprachiasmatic nucleus (SCN), induces locomotor arrhythmia, arrhythmic c-Fos expression, and depression-like behavior. This observation offers valuable insights into the substantial impact of TDP-43 on the behavioral aberrations associated with ALS/FTD. In summary, our study illuminates the significance of TDP-43 in circadian regulation, shedding light on the circadian regulatory mechanisms that may elucidate the pathological underpinnings of ALS/FTD.}, } @article {pmid38585631, year = {2024}, author = {Pinilla-González, V and Montecinos-Barrientos, B and Martin-Kommer, C and Chichiarelli, S and Saso, L and Rodrigo, R}, title = {Exploring antioxidant strategies in the pathogenesis of ALS.}, journal = {Open life sciences}, volume = {19}, number = {1}, pages = {20220842}, pmid = {38585631}, issn = {2391-5412}, abstract = {The central nervous system is essential for maintaining homeostasis and controlling the body's physiological functions. However, its biochemical characteristics make it highly vulnerable to oxidative damage, which is a common factor in neurodegenerative diseases like amyotrophic lateral sclerosis (ALS). ALS is a leading cause of motor neuron disease, characterized by a rapidly progressing and incurable condition. ALS often results in death from respiratory failure within 3-5 years from the onset of the first symptoms, underscoring the urgent need to address this medical challenge. The aim of this study is to present available data supporting the role of oxidative stress in the mechanisms underlying ALS and to discuss potential antioxidant therapies currently in development. These therapies aim to improve the quality of life and life expectancy for patients affected by this devastating disease.}, } @article {pmid38585517, year = {2023}, author = {Firstenfeld, AJ and Listorti, J and Jalaff, N and Loaiza Orozco, CP and Navarrete Gosdenovich, F and Schurr, T}, title = {Add-on treatment with Cerebrolysin improves clinical symptoms in patients with ALS: results from a prospective, single-center, placebo-controlled, randomized, double-blind, phase II study.}, journal = {Journal of medicine and life}, volume = {16}, number = {12}, pages = {1750-1755}, pmid = {38585517}, issn = {1844-3117}, mesh = {Humans ; *Amino Acids ; *Amyotrophic Lateral Sclerosis/drug therapy/diagnosis ; *Neuroprotective Agents/therapeutic use ; Prospective Studies ; Riluzole/therapeutic use ; Treatment Outcome ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a devastating and progressive neurodegenerative disease with limited treatment options available. Cerebrolysin is a drug candidate for the treatment of ALS because of its neuroprotective and neuroregenerative effects. We initiated a pilot clinical study of a combination of Cerebrolysin and riluzole to assess the therapeutic benefit of Cerebrolysin as an add-on treatment on clinical signs and symptoms in outpatients with ALS. Twenty patients with a clinically definitive diagnosis of ALS were enrolled and randomly assigned in a 1:1 ratio to receive Cerebrolysin or placebo. All patients received 50 mg of riluzole PO twice daily as a standard treatment. Patients in the Cerebrolysin group received intravenous injections of 10 mL of Cerebrolysin once daily, five days a week for the first month and three days a week for the next two months. Analysis of the ALS Functional Rating Scale - revised at Month 1 (primary outcome measure), showed a significant treatment effect in favor of Cerebrolysin with a 2.3-point improvement from baseline to Month 1 compared to a 0.9-point decrease in patients on placebo (P=0.005). The effect was maintained over the three-month study period, and the beneficial effect of Cerebrolysin over placebo was also evident in the secondary outcome measures. The safety analysis showed that the combination of riluzole and Cerebrolyisn was well tolerated. Our results demonstrate for the first time a significant clinical effect of Cerebrolysin in improving functional outcomes in patients with ALS and suggest that Cerebrolysin has potential as a novel therapeutic option for ALS.}, } @article {pmid38585368, year = {2024}, author = {Jamet, M and Dupuis, L and Gonzalez De Aguilar, JL}, title = {Oligodendrocytes in amyotrophic lateral sclerosis and frontotemporal dementia: the new players on stage.}, journal = {Frontiers in molecular neuroscience}, volume = {17}, number = {}, pages = {1375330}, pmid = {38585368}, issn = {1662-5099}, abstract = {Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are fatal adult-onset neurodegenerative disorders that share clinical, neuropathological and genetic features, which forms part of a multi-system disease spectrum. The pathological process leading to ALS and FTD is the result of the combination of multiple mechanisms that operate within specific populations of neurons and glial cells. The implication of oligodendrocytes has been the subject of a number of studies conducted on patients and related animal models. In this review we summarize our current knowledge on the alterations specific to myelin and the oligodendrocyte lineage occurring in ALS and FTD. We also consider different ways by which specific oligodendroglial alterations influence neurodegeneration and highlight the important role of oligodendrocytes in these two intrinsically associated neurodegenerative diseases.}, } @article {pmid38583866, year = {2024}, author = {Lee, SH and Hong, WP and Kim, YS and Park, J and Lim, HJ}, title = {Dual-dispatch protocols and return of spontaneous circulation in patients with out-of-hospital cardiac arrest: a nationwide observational study.}, journal = {Clinical and experimental emergency medicine}, volume = {11}, number = {3}, pages = {276-285}, pmid = {38583866}, issn = {2383-4625}, abstract = {OBJECTIVE: The Korean National Fire Agency conducted a pilot project examining Advanced Life Support (ALS) protocols, including epinephrine administration, to improve survival among patients suffering out-of-hospital cardiac arrest (OHCA). In this study, we aimed to evaluate the effects of the Korean National Fire Agency ALS protocol on prehospital return of spontaneous circulation (ROSC) in patients with OHCA.

METHODS: This study included patients with adult-presumed cardiac arrest between January and December 2020. The main factor of interest was ambulance type according to ALS protocol, which was divided into dedicated ALS ambulance (DA), smartphone-based ALS ambulance (SALS), and non-DA, and the main analysis factor was prehospital ROSC. Multivariate logistic regression analysis was performed.

RESULTS: During the study period, a total of 18,031 adult patients with OHCA was treated by the emergency medical services, including 7,520 DAs (41.71%), 2,622 SALSs (14.54%), and 7,889 non-DAs (43.75%). The prehospital ROSC ratio was 13.19% for DA, 11.17% for SALS, and 7.91% for non-DA (P<0.01). Compared with that of the DA group, the odds ratios (95% confidence interval) for prehospital ROSC ratio were 0.97 (0.82-1.15) in the SALS group and 0.57 (0.50-0.65) in the non-DA group. The prehospital ROSC ratio of the DA group was higher than those of the non-DA group and the SALS group.

CONCLUSION: ALS protocol intervention was associated with prehospital ROSC rates. Therefore, continuous efforts to promote systemic implementation of the ALS protocol to improve OHCA outcomes are necessary.}, } @article {pmid38583639, year = {2024}, author = {Genin, EC and di Borgo, PP and Lorivel, T and Hugues, S and Farinelli, M and Mauri-Crouzet, A and Lespinasse, F and Godin, L and Paquis-Flucklinger, V and Petit-Paitel, A}, title = {CHCHD10[S59L/+] mouse model: Behavioral and neuropathological features of frontotemporal dementia.}, journal = {Neurobiology of disease}, volume = {195}, number = {}, pages = {106498}, doi = {10.1016/j.nbd.2024.106498}, pmid = {38583639}, issn = {1095-953X}, mesh = {Animals ; *Frontotemporal Dementia/pathology/genetics ; *Disease Models, Animal ; Mice ; *Mitochondrial Proteins/genetics/metabolism ; Mice, Transgenic ; Behavior, Animal/physiology ; Male ; Long-Term Potentiation/physiology ; Mice, Inbred C57BL ; Hippocampus/pathology/metabolism ; }, abstract = {CHCHD10-related disease causes a spectrum of clinical presentations including mitochondrial myopathy, cardiomyopathy, amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). We generated a knock-in mouse model bearing the p.Ser59Leu (S59L) CHCHD10 variant. Chchd10[S59L/+] mice have been shown to phenotypically replicate the disorders observed in patients: myopathy with mtDNA instability, cardiomyopathy and typical ALS features (protein aggregation, neuromuscular junction degeneration and spinal motor neuron loss). Here, we conducted a comprehensive behavioral, electrophysiological and neuropathological assessment of Chchd10[S59L/+] mice. These animals show impaired learning and memory capacities with reduced long-term potentiation (LTP) measured at the Perforant Pathway-Dentate Gyrus (PP-DG) synapses. In the hippocampus of Chchd10[S59L/+] mice, neuropathological studies show the involvement of protein aggregates, activation of the integrated stress response (ISR) and neuroinflammation in the degenerative process. These findings contribute to decipher mechanisms associated with CHCHD10 variants linking mitochondrial dysfunction and neuronal death. They also validate the Chchd10[S59L/+] mice as a relevant model for FTD, which can be used for preclinical studies to test new therapeutic strategies for this devastating disease.}, } @article {pmid38583636, year = {2024}, author = {do Prado Schneidewind, FCC and de Castilho, PF and Galvão, F and de Andrade Dos Santos, JV and da Silva Dantas, FG and Negri, M and da Silva Pinto, L and Moraes, CAF and Freitas, J and de Souza, PRB and Nogueira, CR and de Oliveira, KMP}, title = {Effects of bioconversion by Battus polydamas on the chemical composition of Aristolochia spp. and evaluation of antimicrobial activity and biocompatibility.}, journal = {Fitoterapia}, volume = {175}, number = {}, pages = {105949}, doi = {10.1016/j.fitote.2024.105949}, pmid = {38583636}, issn = {1873-6971}, mesh = {*Aristolochia/chemistry ; Animals ; *Plant Extracts/pharmacology/chemistry ; Larva/drug effects ; Phytochemicals/pharmacology/isolation & purification ; Microbial Sensitivity Tests ; Humans ; Antioxidants/pharmacology ; Bacillus cereus/drug effects ; Anti-Infective Agents/pharmacology/chemistry ; Anti-Bacterial Agents/pharmacology/chemistry ; Moths/drug effects ; }, abstract = {Aristolochia plants are emblematic from an ethnopharmacological viewpoint and are know to possess numerous biological properties, including antiseptic. However, the medicinal potential of these species is debatable because of their representative chemical constituents, aristolochic acids (AAs) and aristolactams (ALs), which are associated, for instance, with nephropathy and cancer. These contrasting issues have stimulated the development of approaches intended to detoxification of aristoloquiaceous biomasses, among which is included the bioconversion method using larvae of the specialist phytophagous insect Battus polydamas, previously shown to be viable for chemical diversification and to reduce toxicity. Thus, eleven Aristolochia spp. were bioconverted, and the antimicrobial activities of the plant methanolic extracts and its respective bioconversion products were evaluated. The best results were found for Aristolochia esperanzae, Aristolochia gibertii, and Aristolochia ringens against Bacillus cereus, with MIC ranging from 7.8 to 31.25 μg/mL. These three species were selected for chemical, antioxidant, cytotoxic, hemolytic, and mutagenic analyses. Chemical analysis revealed 65 compounds, 21 of them possible bioconversion products. The extracts showed potential to inhibit the formation and degradation of B. cereus biofilms. Extracts of A. gibertii and its bioconverted biomass showed antioxidant activity comparable to dibutylhydroxytoluene (BHT) standard. Bioconversion decreased the hemolytic activity of A. esperanzae and the cytotoxicities of A. esperanzae and A. gibertii. None of the extracts was found to be mutagenic. The bioactivities of the fecal extracts were maintained, and biocompatibility was improved. Therefore, the results obtained in this study reveal positive expectations about the natural detoxification process of the Aristolochia species.}, } @article {pmid38583622, year = {2024}, author = {Newell, ME and Babbrah, A and Aravindan, A and Rathnam, R and Kiernan, R and Driver, EM and Bowes, DA and Halden, RU}, title = {Prevalence rates of neurodegenerative diseases versus human exposures to heavy metals across the United States.}, journal = {The Science of the total environment}, volume = {928}, number = {}, pages = {172260}, doi = {10.1016/j.scitotenv.2024.172260}, pmid = {38583622}, issn = {1879-1026}, mesh = {*Metals, Heavy/analysis ; Humans ; United States/epidemiology ; *Environmental Exposure/statistics & numerical data ; Prevalence ; *Neurodegenerative Diseases/epidemiology/chemically induced ; Environmental Monitoring ; }, abstract = {Novel means are needed to identify individuals and subpopulations susceptible to and afflicted by neurodegenerative diseases (NDDs). This study aimed to utilize geographic distribution of heavy metal sources and sinks to investigate a potential human health risk of developing NDDs. Known or hypothesized environmental factors driving disease prevalence of Alzheimer's Disease (AD), Parkinson's Disease (PD), and amyotrophic lateral sclerosis (ALS) are heavy metals, including arsenic (As), cadmium (Cd), manganese (Mn) and mercury (Hg). Lead (Pb) has been associated with AD and ALS. Analyzable mediums of human exposure to heavy metals (i.e., toxic metals and metalloids), or proxies thereof, include infant blood, topsoil, sewage sludge, and well water. U.S. concentrations of heavy metals in topsoil, sewage sludge, well water, and infant blood were mapped and compared to prevalence rates of major NDDs. Data from federal and state agencies (i.e., CDC, EPA, and the US Geological Survey) on heavy metal concentrations, age distribution, and NDD prevalence rates were geographically represented and statistically analyzed to quantify possible correlations. Aside from an expected significant association between NDD prevalence and age (p < 0.0001), we found significant associations between the prevalence of the sum of three major NDDs with: Pb in topsoil (p = 0.0433); Cd (p < 0.0001) and Pb (p < 0.0001) in sewage sludge; Pb in infant blood (p < 0.0001). Concentrations in sewage sludge of Cd and Pb were significantly correlated with NDD prevalence rates with an odds ratio of 2.91 (2.04, 4.225 95%CI) and 4.084 (3.14, 5.312 95%CI), respectively. The presence of toxic metals in the U.S. environment in multiple matrices, including sewage sludge, was found to be significantly associated with NDD prevalence. This is the first use of sewage sludge as an environmental proxy matrix to infer risk of developing NDDs.}, } @article {pmid38583129, year = {2024}, author = {Thal, DR and Gawor, K and Moonen, S}, title = {Regulated cell death and its role in Alzheimer's disease and amyotrophic lateral sclerosis.}, journal = {Acta neuropathologica}, volume = {147}, number = {1}, pages = {69}, pmid = {38583129}, issn = {1432-0533}, support = {22-AAIIA-963171/ALZ/Alzheimer's Association/United States ; }, mesh = {Humans ; *Alzheimer Disease ; *Amyotrophic Lateral Sclerosis ; *Regulated Cell Death ; Cell Death ; Motor Neurons ; }, abstract = {Despite considerable research efforts, it is still not clear which mechanisms underlie neuronal cell death in neurodegenerative diseases. During the last 20 years, multiple pathways have been identified that can execute regulated cell death (RCD). Among these RCD pathways, apoptosis, necroptosis, pyroptosis, ferroptosis, autophagy-related cell death, and lysosome-dependent cell death have been intensively investigated. Although RCD consists of numerous individual pathways, multiple common proteins have been identified that allow shifting from one cell death pathway to another. Another layer of complexity is added by mechanisms such as the endosomal machinery, able to regulate the activation of some RCD pathways, preventing cell death. In addition, restricted axonal degeneration and synaptic pruning can occur as a result of RCD activation without loss of the cell body. RCD plays a complex role in neurodegenerative processes, varying across different disorders. It has been shown that RCD is differentially involved in Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS), among the most common neurodegenerative diseases. In AD, neuronal loss is associated with the activation of not only necroptosis, but also pyroptosis. In ALS, on the other hand, motor neuron death is not linked to canonical necroptosis, whereas pyroptosis pathway activation is seen in white matter microglia. Despite these differences in the activation of RCD pathways in AD and ALS, the accumulation of protein aggregates immunoreactive for p62/SQSTM1 (sequestosome 1) is a common event in both diseases and many other neurodegenerative disorders. In this review, we describe the major RCD pathways with clear activation in AD and ALS, the main interactions between these pathways, as well as their differential and similar involvement in these disorders. Finally, we will discuss targeting RCD as an innovative therapeutic concept for neurodegenerative diseases, such as AD and ALS. Considering that the execution of RCD or "cellular suicide" represents the final stage in neurodegeneration, it seems crucial to prevent neuronal death in patients by targeting RCD. This would offer valuable time to address upstream events in the pathological cascade by keeping the neurons alive.}, } @article {pmid38582774, year = {2024}, author = {Zhang, H and Guo, H and Li, D and Zhang, Y and Zhang, S and Kang, W and Liu, C and Le, W and Wang, L and Li, D and Dai, B}, title = {Halogen doped graphene quantum dots modulate TDP-43 phase separation and aggregation in the nucleus.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {2980}, pmid = {38582774}, issn = {2041-1723}, support = {82188101//National Natural Science Foundation of China (National Science Foundation of China)/ ; 32171236//National Natural Science Foundation of China (National Science Foundation of China)/ ; 92353302//National Natural Science Foundation of China (National Science Foundation of China)/ ; 32170683//National Natural Science Foundation of China (National Science Foundation of China)/ ; }, mesh = {Humans ; *Graphite ; Phase Separation ; *Quantum Dots ; *Amyotrophic Lateral Sclerosis/metabolism ; DNA-Binding Proteins/metabolism ; }, abstract = {TDP-43 is implicated in the dynamic formation of nuclear bodies and stress granules through phase separation. In diseased states, it can further condense into pathological aggregates in the nucleus and cytoplasm, contributing to the onset of amyotrophic lateral sclerosis. In this study, we evaluate the effect of graphene quantum dots (GQDs) with different functional groups on TDP-43's phase separation and aggregation in various cellular locations. We find that halogen atom-doped GQDs (GQDs-Cl, Cl-GQDs-OH) penetrate the nuclear envelope, inhibiting the assembly of TDP-43 nuclear bodies and stress granules under oxidative stress or hyperosmotic environments, and reduce amyloid aggregates and disease-associated phosphorylation of TDP-43. Mechanistic analysis reveals GQDs-Cl and Cl-GQDs-OH modulate TDP-43 phase separation through hydrophobic and electrostatic interactions. Our findings highlight the potential of GQDs-Cl and Cl-GQDs-OH in modulating nuclear protein condensation and pathological aggregation, offering direction for the innovative design of GQDs to modulate protein phase separation and aggregation.}, } @article {pmid38582030, year = {2024}, author = {van Unnik, JWJ and Meyjes, M and Janse van Mantgem, MR and van den Berg, LH and van Eijk, RPA}, title = {Remote monitoring of amyotrophic lateral sclerosis using wearable sensors detects differences in disease progression and survival: a prospective cohort study.}, journal = {EBioMedicine}, volume = {103}, number = {}, pages = {105104}, pmid = {38582030}, issn = {2352-3964}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/mortality/diagnosis/physiopathology ; Male ; Female ; *Disease Progression ; *Wearable Electronic Devices ; Middle Aged ; Prospective Studies ; Aged ; Accelerometry/instrumentation ; Prognosis ; Remote Sensing Technology/instrumentation/methods ; Adult ; }, abstract = {BACKGROUND: There is an urgent need for objective and sensitive measures to quantify clinical disease progression and gauge the response to treatment in clinical trials for amyotrophic lateral sclerosis (ALS). Here, we evaluate the ability of an accelerometer-derived outcome to detect differential clinical disease progression and assess its longitudinal associations with overall survival in patients with ALS.

METHODS: Patients with ALS wore an accelerometer on the hip for 3-7 days, every 2-3 months during a multi-year observation period. An accelerometer-derived outcome, the Vertical Movement Index (VMI), was calculated, together with predicted disease progression rates, and jointly analysed with overall survival. The clinical utility of VMI was evaluated using comparisons to patient-reported functionality, while the impact of various monitoring schemes on empirical power was explored through simulations.

FINDINGS: In total, 97 patients (70.1% male) wore the accelerometer for 1995 days, for a total of 27,701 h. The VMI was highly discriminatory for predicted disease progression rates, revealing faster rates of decline in patients with a worse predicted prognosis compared to those with a better predicted prognosis (p < 0.0001). The VMI was strongly associated with the hazard for death (HR 0.20, 95% CI: 0.09-0.44, p < 0.0001), where a decrease of 0.19-0.41 unit was associated with reduced ambulatory status. Recommendations for future studies using accelerometery are provided.

INTERPRETATION: The results serve as motivation to incorporate accelerometer-derived outcomes in clinical trials, which is essential for further validation of these markers to meaningful endpoints.

FUNDING: Stichting ALS Nederland (TRICALS-Reactive-II).}, } @article {pmid38580817, year = {2024}, author = {Irwin, KE and Jasin, P and Braunstein, KE and Sinha, IR and Garret, MA and Bowden, KD and Chang, K and Troncoso, JC and Moghekar, A and Oh, ES and Raitcheva, D and Bartlett, D and Miller, T and Berry, JD and Traynor, BJ and Ling, JP and Wong, PC}, title = {Author Correction: A fluid biomarker reveals loss of TDP-43 splicing repression in presymptomatic ALS-FTD.}, journal = {Nature medicine}, volume = {30}, number = {5}, pages = {1504}, doi = {10.1038/s41591-024-02966-z}, pmid = {38580817}, issn = {1546-170X}, } @article {pmid38579683, year = {2024}, author = {Lai, JD and Berlind, JE and Fricklas, G and Lie, C and Urenda, JP and Lam, K and Sta Maria, N and Jacobs, R and Yu, V and Zhao, Z and Ichida, JK}, title = {KCNJ2 inhibition mitigates mechanical injury in a human brain organoid model of traumatic brain injury.}, journal = {Cell stem cell}, volume = {31}, number = {4}, pages = {519-536.e8}, doi = {10.1016/j.stem.2024.03.004}, pmid = {38579683}, issn = {1875-9777}, support = {RF1 NS122060/NS/NINDS NIH HHS/United States ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/etiology/pathology ; Brain/metabolism ; *Brain Injuries, Traumatic/drug therapy/metabolism/therapy ; C9orf72 Protein/metabolism ; DNA-Binding Proteins/metabolism ; *Frontotemporal Dementia/etiology/pathology ; *Neurodegenerative Diseases/etiology/pathology ; *Potassium Channels, Inwardly Rectifying/antagonists & inhibitors/metabolism ; }, abstract = {Traumatic brain injury (TBI) strongly correlates with neurodegenerative disease. However, it remains unclear which neurodegenerative mechanisms are intrinsic to the brain and which strategies most potently mitigate these processes. We developed a high-intensity ultrasound platform to inflict mechanical injury to induced pluripotent stem cell (iPSC)-derived cortical organoids. Mechanically injured organoids elicit classic hallmarks of TBI, including neuronal death, tau phosphorylation, and TDP-43 nuclear egress. We found that deep-layer neurons were particularly vulnerable to injury and that TDP-43 proteinopathy promotes cell death. Injured organoids derived from C9ORF72 amyotrophic lateral sclerosis/frontotemporal dementia (ALS/FTD) patients displayed exacerbated TDP-43 dysfunction. Using genome-wide CRISPR interference screening, we identified a mechanosensory channel, KCNJ2, whose inhibition potently mitigated neurodegenerative processes in vitro and in vivo, including in C9ORF72 ALS/FTD organoids. Thus, targeting KCNJ2 may reduce acute neuronal death after brain injury, and we present a scalable, genetically flexible cerebral organoid model that may enable the identification of additional modifiers of mechanical stress.}, } @article {pmid38577970, year = {2024}, author = {Barreto-Núñez, R and Béland, LC and Boutej, H and Picher-Martel, V and Dupré, N and Barbeito, L and Kriz, J}, title = {Chronically activated microglia in ALS gradually lose their immune functions and develop unconventional proteome.}, journal = {Glia}, volume = {72}, number = {7}, pages = {1319-1339}, doi = {10.1002/glia.24531}, pmid = {38577970}, issn = {1098-1136}, support = {//ALS Society of Canada/ ; //Fondation Brain Canada/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/metabolism/immunology/pathology/genetics ; *Microglia/metabolism/immunology ; Animals ; *Proteome/metabolism ; Mice ; *Mice, Transgenic ; Spinal Cord/metabolism/pathology/immunology ; Disease Models, Animal ; Phagocytosis/physiology ; Humans ; Female ; Mice, Inbred C57BL ; Male ; }, abstract = {Neuroinflammation and chronic activation of microglial cells are the prominent features of amyotrophic lateral sclerosis (ALS) pathology. While alterations in the mRNA profile of diseased microglia have been well documented, the actual microglia proteome remains poorly characterized. Here we performed a functional characterization together with proteome analyses of microglial cells at different stages of disease in the SOD1-G93A model of ALS. Functional analyses of microglia derived from the lumbar spinal cord of symptomatic mice revealed: (i) remarkably high mitotic index (close to 100% cells are Ki67+) (ii) significant decrease in phagocytic capacity when compared to age-matched control microglia, and (iii) diminished response to innate immune challenges in vitro and in vivo. Proteome analysis revealed a development of two distinct molecular signatures at early and advanced stages of disease. While at early stages of disease, we identified several proteins implicated in microglia immune functions such as GPNMB, HMBOX1, at advanced stages of disease microglia signature at protein level was characterized with a robust upregulation of several unconventional proteins including rootletin, major vaults proteins and STK38. Upregulation of GPNMB and rootletin has been also found in the spinal cord samples of sporadic ALS. Remarkably, the top biological functions of microglia, in particular in the advanced disease, were not related to immunity/immune response, but were highly enriched in terms linked to RNA metabolism. Together, our results suggest that, over the course of disease, chronically activated microglia develop unconventional protein signatures and gradually lose their immune identity ultimately turning into functionally inefficient immune cells.}, } @article {pmid38577753, year = {2024}, author = {Yellepeddi, VK and Race, JA and McFarland, MM and Constance, JE and Fanaeian, E and Murphy, NA}, title = {Effectiveness of atropine in managing sialorrhea: A systematic review and meta-analysis.}, journal = {International journal of clinical pharmacology and therapeutics}, volume = {62}, number = {6}, pages = {267-277}, doi = {10.5414/CP204538}, pmid = {38577753}, issn = {0946-1965}, mesh = {*Sialorrhea/drug therapy ; Humans ; *Atropine/therapeutic use ; Treatment Outcome ; Salivation/drug effects ; }, abstract = {OBJECTIVES: To describe the efficacy of atropine in controlling salivary flow in patients with sialorrhea or drooling.

MATERIALS AND METHODS: We included randomized controlled studies, quasi-randomized trials, case reports, clinical trials, systematic reviews, and meta-analyses assessing the use of atropine in patients with sialorrhea or drooling. The endpoints were reduction in salivary flow rate, amount of saliva secreted, reduction in clinical symptoms of sialorrhea, death rattle intensity, or reduction in drooling intensity as measured by an objective scale such as the drooling intensity scale.

RESULTS: A total of 56 studies with 2,378 patients were included in the systematic review. The underlying disease states included brain injury, amyotrophic lateral sclerosis, cerebral palsy, clozapine- and perphenazine-induced sialorrhea, Parkinson's disease, and terminal illness. The routes of atropine administration included sublingual, intravenous, subcutaneous, oral tablet or solution, and direct injection of atropine into parotid glands or at the base of the tongue. The generalized estimated equation regression models showed that sublingual administration is superior to oral and subcutaneous routes.

CONCLUSION: Atropine is efficacious in managing sialorrhea in most disease states. Sublingual administration of atropine is superior to other routes of administration in reducing salivary flow in patients with sialorrhea.}, } @article {pmid38576758, year = {2024}, author = {Gonzalez, FM and Cohens, FG}, title = {Predicting outcomes after kidney transplantation: Can Pareto's rules help us to do so?.}, journal = {World journal of transplantation}, volume = {14}, number = {1}, pages = {90149}, pmid = {38576758}, issn = {2220-3230}, abstract = {Kidney transplantation is the best option for kidney replacement therapy, even considering that most of the times the grafts do not survive as long as their recipients. In the Khalil et al's experience, published in this issue of the Journal, they analyze their second kidney graft survival and describe those significant predictors of early loss. This editorial comments on the results and put in perspec tive that most of the times, long-term graft survival could be inadvertently jeopardized if the immunosuppressive therapy is reduced or withdrawn for any reason, and that it could happen frequently if the transplant physician intends to innovate with the clinical care without proper evidence-based data.}, } @article {pmid38576194, year = {2024}, author = {Rutkove, SB and McIlduff, CE and Stommel, E and Levy, S and Smith, C and Gutierrez, H and Verga, S and Samaan, S and Yator, C and Nanda, A and Pastel, L and Doussan, A and Phipps, K and Murphy, E and Halter, R}, title = {Assessing pulmonary function in ALS using electrical impedance tomography.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {25}, number = {5-6}, pages = {581-588}, pmid = {38576194}, issn = {2167-9223}, support = {R21 NS118434/NS/NINDS NIH HHS/United States ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology/diagnostic imaging/diagnosis ; Female ; Male ; Middle Aged ; *Electric Impedance ; *Respiratory Function Tests/methods ; Aged ; Tomography/methods ; Adult ; Reproducibility of Results ; Vital Capacity/physiology ; Lung/physiopathology/diagnostic imaging ; }, abstract = {OBJECTIVE: We sought to determine whether thoracic electrical impedance tomography (EIT) could characterize pulmonary function in amyotrophic lateral sclerosis (ALS) patients, including those with facial weakness. Thoracic EIT is a noninvasive, technology in which a multi-electrode belt is placed across the chest, producing real-time impedance imaging of the chest during breathing.

METHODS: We enrolled 32 ALS patients and 32 age- and sex-matched healthy controls (HCs) without underlying lung disease. All participants had EIT measurements performed simultaneously with standard pulmonary function tests (PFTs), including slow and forced vital capacity (SVC and FVC) in upright and supine positions and maximal inspiratory and expiratory pressures (MIPs and MEPs, respectively). Intraclass correlation coefficients (ICCs) were calculated to assess the immediate reproducibility of EIT measurements and Pearson's correlations were used to explore the relationships between EIT and PFT values.

RESULTS: Data from 30 ALS patients and 27 HCs were analyzed. Immediate upright SVC reproducibility was very high (ICC 0.98). Correlations were generally strongest between EIT and spirometry measures, with R values ranging from 0.64 to 0.82 (p < 0.001) in the ALS cohort. There were less robust correlations between EIT values and both MIPs and MEPs in the ALS patients, with R values ranging from 0.33 to 0.44. There was no significant difference for patients with and without facial weakness. There were no reported adverse events.

CONCLUSION: EIT-based pulmonary measures hold the promise of providing an alternative approach for lung function assessment in ALS patients. Based on these early results, further development and study of this technology are warranted.}, } @article {pmid38575965, year = {2024}, author = {Daudelin, D and Westerhaus, A and Zhang, N and Leyder, E and Savonenko, A and Sockanathan, S}, title = {Loss of GDE2 leads to complex behavioral changes including memory impairment.}, journal = {Behavioral and brain functions : BBF}, volume = {20}, number = {1}, pages = {7}, pmid = {38575965}, issn = {1744-9081}, support = {RF1AG062671/NH/NIH HHS/United States ; F31 AG079539/AG/NIA NIH HHS/United States ; T32NS091018/NH/NIH HHS/United States ; T32GM007445/NH/NIH HHS/United States ; RF1 AG062671/AG/NIA NIH HHS/United States ; T32 NS091018/NS/NINDS NIH HHS/United States ; }, mesh = {Aged ; Animals ; Female ; Humans ; Mice ; *Alzheimer Disease/genetics ; *Amyotrophic Lateral Sclerosis/genetics ; *Frontotemporal Dementia/genetics ; Memory ; Memory Disorders/genetics ; Mice, Transgenic ; *Neurodegenerative Diseases/genetics ; }, abstract = {BACKGROUND: Alzheimer's disease (AD) and amyotrophic lateral sclerosis/frontotemporal dementia (ALS/FTD) are debilitating neurodegenerative diseases for which there are currently no cures. Familial cases with known genetic causes make up less than 10% of these diseases, and little is known about the underlying mechanisms that contribute to sporadic disease. Accordingly, it is important to expand investigations into possible pathways that may contribute to disease pathophysiology. Glycerophosphodiester phosphodiesterase 2 (GDE2 or GDPD5) is a membrane-bound enzyme that acts at the cell surface to cleave the glycosylphosphatidylinositol (GPI)-anchor that tethers distinct proteins to the membrane. GDE2 abnormally accumulates in intracellular compartments in the brain of patients with AD, ALS, and ALS/FTD, indicative of GDE2 dysfunction. Mice lacking GDE2 (Gde2KO) show neurodegenerative changes such as neuronal loss, reduced synaptic proteins and synapse loss, and increased Aβ deposition, raising the possibility that GDE2 disruption in disease might contribute to disease pathophysiology. However, the effect of GDE2 loss on behavioral function and learning/memory has not been characterized.

RESULTS: Here, we show that GDE2 is expressed throughout the adult mouse brain in areas including the cortex, hippocampus, habenula, thalamus, and amygdala. Gde2KO and WT mice were tested in a set of behavioral tasks between 7 and 16 months of age. Compared to WT, Gde2KO mice display moderate hyperactivity that becomes more pronounced with age across a variety of behavioral tests assessing novelty-induced exploratory activity. Additionally, Gde2KO mice show reduced startle response, with females showing additional defects in prepulse inhibition. No changes in anxiety-associated behaviors were found, but Gde2KOs show reduced sociability. Notably, aged Gde2KO mice demonstrate impaired short/long-term spatial memory and cued fear memory/secondary contextual fear acquisition.

CONCLUSIONS: Taken together, these observations suggest that loss of GDE2 leads to behavioral deficits, some of which are seen in neurodegenerative disease models, implying that loss of GDE2 may be an important contributor to phenotypes associated with neurodegeneration.}, } @article {pmid38575486, year = {2024}, author = {Chandran, SK and Doucet, M}, title = {Neurogenic Dysphagia.}, journal = {Otolaryngologic clinics of North America}, volume = {57}, number = {4}, pages = {589-597}, doi = {10.1016/j.otc.2024.02.023}, pmid = {38575486}, issn = {1557-8259}, mesh = {Humans ; *Deglutition Disorders/etiology/therapy/diagnosis ; *Amyotrophic Lateral Sclerosis/complications/therapy ; Multiple Sclerosis/complications ; Parkinson Disease/complications ; Stroke/complications ; }, abstract = {This article provides an overview of neurogenic dysphagia, describing the evaluation and management of swallowing dysfunction in various neurologic diseases. The article will focus on stroke, Parkinson's disease, amyotrophic lateral sclerosis, and multiple sclerosis.}, } @article {pmid38575127, year = {2024}, author = {Zhang, T and Wang, Z and Li, Y and Zhou, B and Liu, Y and Li, J and Wang, R and Lv, Q and Li, C and Zhang, Y and Su, R}, title = {Genetic diversity and population structure in five Inner Mongolia cashmere goat populations using whole-genome genotyping.}, journal = {Animal bioscience}, volume = {37}, number = {7}, pages = {1168-1176}, pmid = {38575127}, issn = {2765-0189}, support = {2021ZD0012//Science and technology major project of Inner Mongolia Autonomous Region/ ; 2021GG0086//Inner Mongolia Autonomous Region Science and Technology Research Project/ ; NJYT22038//Inner Mongolia Inner Mongolia Autonomous Region/ ; NMGIRT2322//Program for Innovative Research Team in Universities of Inner Mongolia Autonomous Region/ ; CARS-39//China Agriculture Research System of MOF and MARA/ ; }, abstract = {OBJECTIVE: As a charismatic species, cashmere goats have rich genetic resources. In the Inner Mongolia Autonomous Region, there are three cashmere goat varieties named and approved by the state. These goats are renowned for their high cashmere production and superior cashmere quality. Therefore, it is vitally important to protect their genetic resources as they will serve as breeding material for developing new varieties in the future.

METHODS: Three breeds including Inner Mongolia cashmere goats (IMCG), Hanshan White cashmere goats (HS), and Ujimqin white cashmere goats (WZMQ) were studied. IMCG were of three types: Aerbas (AEBS), Erlangshan (ELS), and Alashan (ALS). Nine DNA samples were collected for each population, and they were genomically re-sequenced to obtain high-depth data. The genetic diversity parameters of each population were estimated to determine selection intensity. Principal component analysis, phylogenetic tree construction and genetic differentiation parameter estimation were performed to determine genetic relationships among populations.

RESULTS: Samples from the 45 individuals from the five goat populations were sequenced, and 30,601,671 raw single nucleotide polymorphisms (SNPs) obtained. Then, variant calling was conducted using the reference genome, and 17,214,526 SNPs were retained after quality control. Individual sequencing depth of individuals ranged from 21.13× to 46.18×, with an average of 28.5×. In the AEBS, locus polymorphism (79.28) and expected heterozygosity (0.2554) proportions were the lowest, and the homologous consistency ratio (0.1021) and average inbreeding coefficient (0.1348) were the highest, indicating that this population had strong selection intensity. Conversely, ALS and WZMQ selection intensity was relatively low. Genetic distance between HS and the other four populations was relatively high, and genetic exchange existed among the other four populations.

CONCLUSION: The Inner Mongolia cashmere goat (AEBS type) population has a relatively high selection intensity and a low genetic diversity. The IMCG (ALS type) and WZMQ populations had relatively low selection intensity and high genetic diversity. The genetic distance between HS and the other four populations was relatively high, with a moderate degree of differentiation. Overall, these genetic variations provide a solid foundation for resource identification of Inner Mongolia Autonomous Region cashmere goats in the future.}, } @article {pmid38575115, year = {2024}, author = {Temkin-Greener, H and Guo, W and McGarry, B and Cai, S}, title = {Serious Mental Illness in Assisted Living Communities: Association with Nursing Home Placement.}, journal = {Journal of the American Medical Directors Association}, volume = {25}, number = {5}, pages = {917-922}, pmid = {38575115}, issn = {1538-9375}, support = {R01 HS026893/HS/AHRQ HHS/United States ; }, mesh = {Humans ; *Mental Disorders ; Medicare ; Aged ; Aged, 80 and over ; Dementia/epidemiology ; United States ; *Nursing Homes ; *Assisted Living Facilities ; Depressive Disorder, Major/epidemiology ; Bipolar Disorder/epidemiology ; Schizophrenia/epidemiology ; Retrospective Studies ; Male ; Female ; }, abstract = {OBJECTIVES: Assess prevalence of serious mental illness (SMI) alone, and co-occurring with Alzheimer disease and related dementias (ADRD), among Medicare beneficiaries in assisted living (AL). Examine the association between permanent nursing home (NH) placement and SMI, among residents with and without ADRD.

DESIGN: 2018-2019 retrospective cohort of Medicare beneficiaries in AL. Residents were followed for up to 2 years to track their NH placement. We used data from the Medicare Enrollment Database, the Medicare Beneficiary Summary File, Minimum Data Set, and a national directory of state-licensed AL communities. AL residents were identified using a validated, previously reported 9-digit zip code methodology.

SETTING AND PARTICIPANTS: A cross-sectional study sample included 289,350 Medicare beneficiaries in 17,265 AL communities across 50 states and in the District of Columbia.

METHODS: The outcome was permanent NH placement: a continuous stay for more than 90 days. Key independent variable was presence of SMI-schizophrenia, bipolar disorder, and major depression. Other covariates included sociodemographic factors and presence of other chronic conditions, including ADRD. A linear probability model with robust SEs, and AL-level random effects, was used to test the association between SMI diagnoses, ADRD, and their interactions on NH placement.

RESULTS: More than half (55.65%) of AL residents had a diagnosis of SMI, among them 93.2% had major depression, 28.5% schizophrenia, and 22.2% bipolar disorder. Individuals with schizophrenia and bipolar disorder had a significantly lower probability of NH placement, a 32% and a 15% decrease relative to the cohort mean, respectively. Placement risk was significantly greater for residents with ADRD compared to those without, increasing for those who also had schizophrenia or bipolar disorder, 12.9% and 1.5% relative to the sample mean, respectively.

CONCLUSION AND IMPLICATIONS: Presence of schizophrenia and bipolar disorder, in conjunction with ADRD, significantly increases the risk of long-term NH placement, suggesting that ALs may not be well prepared to care for these residents.}, } @article {pmid38574876, year = {2024}, author = {Watt, CL and Smith, IC and Rice, J and Murphy, R and Breiner, A and Duff, MLV and Nogo, D and Bush, SH and McNeely, S and Buenger, U and Zehrt, B and Zwicker, J}, title = {Qualitative Analysis of Initial Palliative Care Consultations in Amyotrophic Lateral Sclerosis.}, journal = {Journal of pain and symptom management}, volume = {68}, number = {1}, pages = {43-52.e2}, doi = {10.1016/j.jpainsymman.2024.03.024}, pmid = {38574876}, issn = {1873-6513}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy ; *Palliative Care ; Male ; Female ; Middle Aged ; *Caregivers/psychology ; Aged ; *Referral and Consultation ; Prospective Studies ; *Qualitative Research ; COVID-19 ; Adult ; Advance Care Planning ; Feasibility Studies ; }, abstract = {BACKGROUND: Palliative care (PC) benefits patients with amyotrophic lateral sclerosis (ALS), however the needs of patients and caregivers and the optimal timing of PC discussions remains unclear. This study reports the analysis of PC consult notes from a larger feasibility trial. The specific aims of this analysis were to i) identify the PC needs of patients with ALS via qualitative analysis and ii) identify characteristics of patients and caregivers that could predict specific PC needs.

METHODS: This study was nested within a nonrandomized, prospective study of patients with ALS (and their caregivers) being treated at a multidisciplinary ALS clinic. Exclusion criteria of the main study were age <18 years, inability to complete questionnaires, and prior receipt of PC. All patients were offered a PC consultation (PCC); those who accepted were included in this nested study. Consultation notes were reviewed and thematic and content analyses were conducted. The occurrence of themes across patient and caregiver contextual variables were examined.

RESULTS: Thirty-two PCCs were completed between October 2020 and April 2022. Six major themes were identified: PC roles (with subthemes encompassing the spectrum of specialist PC practice including symptom management and advance care planning), engagement with PC, patients' concerns for their caregivers, caregiver-specific concerns, finances, and COVID-19. An average of 12 topics were discussed per PCC (range = 3-22). Discussion of advance care planning, care coordination, and symptom management was common, and these topics were not discussed more frequently in PCCs with patients with lower functional status, more bulbar symptoms, or lower quality of life. Time from diagnosis did not impact topics of discussion. Patients reporting more symptoms of depression more frequently required psychological support, particularly regarding loss of independence, employment, and leisure activities.

DISCUSSION: Patients with ALS and their caregivers have a wide range of PC needs. These needs vary irrespective of time from diagnosis, functional status, or quality of life, therefore PCC is recommended for all patients with ALS. PCC should be individualized based on patient and caregiver preferences.

The study was registered with ClinicalTrials.gov (NCT04257760; https://clinicaltrials.gov/ct2/show/NCT04257760) on February 6, 2020. The first enrollment occurred on October 20, 2020.}, } @article {pmid38574339, year = {2024}, author = {Meyers, EE and Brizzi, KT}, title = {Analgesic Strategies in Patients With Amyotrophic Lateral Sclerosis #477.}, journal = {Journal of palliative medicine}, volume = {27}, number = {4}, pages = {565-566}, doi = {10.1089/jpm.2024.0014}, pmid = {38574339}, issn = {1557-7740}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy ; Patients ; }, } @article {pmid38570593, year = {2024}, author = {van Stuijvenberg, OC and Broekman, MLD and Wolff, SEC and Bredenoord, AL and Jongsma, KR}, title = {Developer perspectives on the ethics of AI-driven neural implants: a qualitative study.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {7880}, pmid = {38570593}, issn = {2045-2322}, support = {17619//Nederlandse Organisatie voor Wetenschappelijk Onderzoek/ ; }, mesh = {*Artificial Intelligence ; Reproducibility of Results ; Qualitative Research ; Focus Groups ; *Cochlear Implants ; }, abstract = {Convergence of neural implants with artificial intelligence (AI) presents opportunities for the development of novel neural implants and improvement of existing neurotechnologies. While such technological innovation carries great promise for the restoration of neurological functions, they also raise ethical challenges. Developers of AI-driven neural implants possess valuable knowledge on the possibilities, limitations and challenges raised by these innovations; yet their perspectives are underrepresented in academic literature. This study aims to explore perspectives of developers of neurotechnology to outline ethical implications of three AI-driven neural implants: a cochlear implant, a visual neural implant, and a motor intention decoding speech-brain-computer-interface. We conducted semi-structured focus groups with developers (n = 19) of AI-driven neural implants. Respondents shared ethically relevant considerations about AI-driven neural implants that we clustered into three themes: (1) design aspects; (2) challenges in clinical trials; (3) impact on users and society. Developers considered accuracy and reliability of AI-driven neural implants conditional for users' safety, authenticity, and mental privacy. These needs were magnified by the convergence with AI. Yet, the need for accuracy and reliability may also conflict with potential benefits of AI in terms of efficiency and complex data interpretation. We discuss strategies to mitigate these challenges.}, } @article {pmid38570009, year = {2024}, author = {Fernández Comaduran, M and Minotti, S and Jacob-Tomas, S and Rizwan, J and Larochelle, N and Robitaille, R and Sephton, CF and Vera, M and Nalbantoglu, JN and Durham, HD}, title = {Impact of histone deacetylase inhibition and arimoclomol on heat shock protein expression and disease biomarkers in primary culture models of familial ALS.}, journal = {Cell stress & chaperones}, volume = {29}, number = {3}, pages = {359-380}, pmid = {38570009}, issn = {1466-1268}, mesh = {*Amyotrophic Lateral Sclerosis/metabolism/genetics/drug therapy ; *Histone Deacetylase Inhibitors/pharmacology ; *Biomarkers/metabolism ; *DNA-Binding Proteins/metabolism/genetics ; Humans ; *Motor Neurons/metabolism/drug effects/pathology ; Animals ; HSP70 Heat-Shock Proteins/metabolism/genetics ; HSC70 Heat-Shock Proteins/metabolism/genetics ; Hydroxylamines/pharmacology ; Cells, Cultured ; RNA-Binding Protein FUS/metabolism/genetics ; Superoxide Dismutase-1/metabolism/genetics ; }, abstract = {Protein misfolding and mislocalization are common themes in neurodegenerative disorders, including motor neuron disease, and amyotrophic lateral sclerosis (ALS). Maintaining proteostasis is a crosscutting therapeutic target, including the upregulation of heat shock proteins (HSP) to increase chaperoning capacity. Motor neurons have a high threshold for upregulating stress-inducible HSPA1A, but constitutively express high levels of HSPA8. This study compared the expression of these HSPs in cultured motor neurons expressing three variants linked to familial ALS: TAR DNA binding protein 43 kDa (TDP-43)[G348C], fused in sarcoma (FUS)[R521G], or superoxide dismutase I (SOD1)[G93A]. All variants were poor inducers of Hspa1a, and reduced levels of Hspa8 mRNA and protein, indicating multiple compromises in chaperoning capacity. To promote HSP expression, cultures were treated with the putative HSP coinducer, arimoclomol, and class I histone deacetylase inhibitors, to promote active chromatin for transcription, and with the combination. Treatments had variable, often different effects on the expression of Hspa1a and Hspa8, depending on the ALS variant expressed, mRNA distribution (somata and dendrites), and biomarker of toxicity measured (histone acetylation, maintaining nuclear TDP-43 and the neuronal Brm/Brg-associated factor chromatin remodeling complex component Brg1, mitochondrial transport, FUS aggregation). Overall, histone deacetylase inhibition alone was effective on more measures than arimoclomol. As in the FUS model, arimoclomol failed to induce HSPA1A or preserve Hspa8 mRNA in the TDP-43 model, despite preserving nuclear TDP-43 and Brg1, indicating neuroprotective properties other than HSP induction. The data speak to the complexity of drug mechanisms against multiple biomarkers of ALS pathogenesis, as well as to the importance of HSPA8 for neuronal proteostasis in both somata and dendrites.}, } @article {pmid38568213, year = {2024}, author = {Feichtner, A and Enzler, F and Kugler, V and Hoppe, K and Mair, S and Kremser, L and Lindner, H and Huber, RG and Stelzl, U and Stefan, E and Torres-Quesada, O}, title = {Phosphorylation of the compartmentalized PKA substrate TAF15 regulates RNA-protein interactions.}, journal = {Cellular and molecular life sciences : CMLS}, volume = {81}, number = {1}, pages = {162}, pmid = {38568213}, issn = {1420-9071}, support = {255310//Österreichische Krebshilfe Tirol/ ; P 35159/FWF_/Austrian Science Fund FWF/Austria ; P32960//Austrian Science Fund/ ; I5406//Austrian Science Fund/ ; P 32960/FWF_/Austrian Science Fund FWF/Austria ; 235872//Tiroler Wissenschaftsförderung/ ; P30441//Austrian Science Fund/ ; P 30441/FWF_/Austrian Science Fund FWF/Austria ; Concrete//Horizon 2020 Framework Programme/ ; P35159//Austrian Science Fund/ ; }, mesh = {Humans ; Cyclic AMP-Dependent Protein Kinases ; Phosphorylation ; Cyclic AMP ; *Amyotrophic Lateral Sclerosis ; RNA ; *TATA-Binding Protein Associated Factors ; }, abstract = {Spatiotemporal-controlled second messengers alter molecular interactions of central signaling nodes for ensuring physiological signal transmission. One prototypical second messenger molecule which modulates kinase signal transmission is the cyclic-adenosine monophosphate (cAMP). The main proteinogenic cellular effectors of cAMP are compartmentalized protein kinase A (PKA) complexes. Their cell-type specific compositions precisely coordinate substrate phosphorylation and proper signal propagation which is indispensable for numerous cell-type specific functions. Here we present evidence that TAF15, which is implicated in the etiology of amyotrophic lateral sclerosis, represents a novel nuclear PKA substrate. In cross-linking and immunoprecipitation experiments (iCLIP) we showed that TAF15 phosphorylation alters the binding to target transcripts related to mRNA maturation, splicing and protein-binding related functions. TAF15 appears to be one of multiple PKA substrates that undergo RNA-binding dynamics upon phosphorylation. We observed that the activation of the cAMP-PKA signaling axis caused a change in the composition of a collection of RNA species that interact with TAF15. This observation appears to be a broader principle in the regulation of molecular interactions, as we identified a significant enrichment of RNA-binding proteins within endogenous PKA complexes. We assume that phosphorylation of RNA-binding domains adds another layer of regulation to binary protein-RNAs interactions with consequences to RNA features including binding specificities, localization, abundance and composition.}, } @article {pmid38568048, year = {2024}, author = {Grassano, M and Moglia, C and Palumbo, F and Koumantakis, E and Cugnasco, P and Callegaro, S and Canosa, A and Manera, U and Vasta, R and De Mattei, F and Matteoni, E and Fuda, G and Salamone, P and Marchese, G and Casale, F and De Marchi, F and Mazzini, L and Mora, G and Calvo, A and Chiò, A}, title = {Sex Differences in Amyotrophic Lateral Sclerosis Survival and Progression: A Multidimensional Analysis.}, journal = {Annals of neurology}, volume = {96}, number = {1}, pages = {159-169}, doi = {10.1002/ana.26933}, pmid = {38568048}, issn = {1531-8249}, support = {2017SNW5MB//Ministero dell'Università e della Ricerca/ ; RF-2016-02362405//Ministero della Salute/ ; //American Academy of Neurology/ ; //Joint Programme Neurodegenerative Disease Research (JPND)/ ; 259867//Seventh Framework Programme/ ; //ALS Association/ ; //American Brain Foundation/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/mortality/physiopathology ; Male ; Female ; *Disease Progression ; Middle Aged ; Aged ; *Sex Characteristics ; Vital Capacity/physiology ; Cohort Studies ; Registries ; Sex Factors ; Prognosis ; Survival Analysis ; Adult ; }, abstract = {OBJECTIVE: To investigate sex-related differences in amyotrophic lateral sclerosis (ALS) prognosis and their contributing factors.

METHODS: Our primary cohort was the Piemonte and Aosta Register for ALS (PARALS); the Pooled Resource Open-Access ALS Clinical Trials (PRO-ACT) and the Answer ALS databases were used for validation. Survival analyses were conducted accounting for age and onset site. The roles of forced vital capacity and weight decline were explored through a causal mediation analysis. Survival and disease progression rates were also evaluated after propensity score matching.

RESULTS: The PARALS cohort included 1,890 individuals (44.8% women). Men showed shorter survival when stratified by onset site (spinal onset HR 1.20, 95% CI 1.00-1.44, p = 0.0439; bulbar onset HR 1.36, 95% CI 1.09-1.70, p = 0.006917), although women had a steeper functional decline (+0.10 ALSFRS-R points/month, 95% CI 0.07-0.15, p < 0.00001) regardless of onset site. Instead, men showed worse respiratory decline (-4.2 forced vital capacity%/month, 95% CI -6.3 to -2.2, p < 0.0001) and faster weight loss (-0.15 kg/month, 95% CI -0.25 to -0.05, p = 0.0030). Causal mediation analysis showed that respiratory function and weight loss were pivotal in sex-related survival differences. Analysis of patients from PRO-ACT (n = 1,394, 40.9% women) and Answer ALS (n = 849, 37.2% women) confirmed these trends.

INTERPRETATION: The shorter survival in men is linked to worse respiratory function and weight loss rather than a faster disease progression. These findings emphasize the importance of considering sex-specific factors in understanding ALS pathophysiology and designing tailored therapeutic strategies. ANN NEUROL 2024;96:159-169.}, } @article {pmid38568044, year = {2024}, author = {Calvo, A and Moglia, C and Canosa, A and Manera, U and Vasta, R and Grassano, M and Daviddi, M and De Mattei, F and Matteoni, E and Gallone, S and Brunetti, M and Sbaiz, L and Cabras, S and Peotta, L and Palumbo, F and Iazzolino, B and Mora, G and Chiò, A}, title = {High Frequency of Cognitive and Behavioral Impairment in Amyotrophic Lateral Sclerosis Patients with SOD1 Pathogenic Variants.}, journal = {Annals of neurology}, volume = {96}, number = {1}, pages = {150-158}, doi = {10.1002/ana.26928}, pmid = {38568044}, issn = {1531-8249}, support = {RF-2016-02362405//Ministero della Salute/ ; 101017598//HORIZON EUROPE Health/ ; 2017SNW5MB//Ministero dell'Università e della Ricerca/ ; 259867//FP7 Health/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/psychology/complications ; Male ; Female ; *Superoxide Dismutase-1/genetics ; Aged ; Middle Aged ; *Cognitive Dysfunction/genetics/psychology ; Adult ; }, abstract = {OBJECTIVE: While the cognitive-behavioral characteristics of amyotrophic lateral sclerosis (ALS) patients carrying C9orf72 pathological repeat expansion have been extensively studied, our understanding of those carrying SOD1 variants is mostly based on case reports. The aim of this paper is to extensively explore the cognitive-behavioral characteristics of a cohort of ALS patients carrying pathogenetic variants of SOD1 gene, comparing them to patients without pathogenetic variants of 46 ALS-related genes (wild-type [WT]-ALS) and healthy controls.

METHODS: All ALS patients seen at the Turin ALS expert center in the 2009-2021 period who underwent both cognitive/behavioral and extensive genetic testing were eligible to be included in the study. Only patients with SOD1 pathogenetic variants (n = 28) (SOD1-ALS) and WT-ALS (n = 829) were enrolled in the study. A series of 129 controls was also included.

RESULTS: Among the 28 SOD1-ALS patients, 16 (57.1%) had normal cognitive function, 5 (17.9%) isolated cognitive impairment (ALSci) (17.9%), 6 (21.4%) isolated behavioral impairment (ALSbi), 1 (3.6%) cognitive and behavioral impairment (ALScbi), and no one ALS-FTD. SOD1-ALS performed worse than controls in all explored domains, in particular Social Cognition and Language domains. SOD1-ALS patients had similar scores in all tests compared to WT-ALS, except the Story-based Empathy Task (SET), where they performed worse.

INTERPRETATION: Cognitive-behavioral impairment is much more common in SOD1 patients than previously assumed. SOD1-ALS are characterized by a more frequent impairment of Social Cognition and, less markedly, of Language domains. These findings have relevant implication both in the clinical and in the research setting, also considering recently approved treatment for SOD1-ALS. ANN NEUROL 2024;96:150-158.}, } @article {pmid38567799, year = {2024}, author = {Wang, XJ and Cornell, PY and Belanger, E and Thomas, KS}, title = {Do end-of-life outcomes differ by assisted living memory-care designation?.}, journal = {Journal of the American Geriatrics Society}, volume = {72}, number = {8}, pages = {2491-2499}, pmid = {38567799}, issn = {1532-5415}, support = {R01 AG057746/AG/NIA NIH HHS/United States ; R01 AG066902/AG/NIA NIH HHS/United States ; R01AG066902/AG/NIA NIH HHS/United States ; R01AG057746/AG/NIA NIH HHS/United States ; }, mesh = {Humans ; Male ; Female ; *Assisted Living Facilities/statistics & numerical data ; Aged, 80 and over ; United States ; *Terminal Care/statistics & numerical data ; Aged ; *Medicare/statistics & numerical data ; Prospective Studies ; *Hospice Care/statistics & numerical data ; Alzheimer Disease/mortality/therapy ; Dementia/mortality/therapy ; }, abstract = {BACKGROUND: Residential care/assisted living (RC/AL) is an increasingly common place of end-of-life care for persons with Alzheimer's disease and related dementia (ADRD), who have unique care needs as their health declines. Approximately 22% of RC/ALs provide specialized memory care (memory-care RC/AL). Understanding how end-of-life outcomes differ by memory care among residents with ADRD could facilitate aging/dying in place for this population. The objective of this paper is to examine if end-of-life outcomes (i.e., mortality, hospice use, and number of days receiving hospice in the last month of life) differ between residents with ADRD who moved to memory-care RC/AL, compared with residents with ADRD who moved to RC/AL without memory care (general RC/AL).

METHODS: Prospective cohort of 15,152 fee-for-service Medicare beneficiaries with ADRD who moved to large RC/AL (> = 25 beds) between 2016 and 2018. We used inverse probability treatment weighting to account for observable differences between memory-care and general RC/AL residents. Two-part models estimated the difference by memory care in the number of days receiving hospice care in the last months of life among RC/AL decedents.

RESULTS: The unadjusted mortality rates were 13.4% in general RC/AL and 15.8% in memory-care RC/AL with an adjusted difference of 1.3 percentage points higher mortality among memory-care RC/AL residents (p = 0.04). Hospice use was 8% and 10.6% among general and memory-care RC/AL residents, respectively, with an adjusted difference of 1.4 percentage points (p = 0.01) higher in memory care. Two-part models showed that decedents in memory-care RC/AL spent about 1.4 more days receiving hospice care in the last month of life (p = 0.02).

CONCLUSION: We find a higher mortality rate and higher rate of hospice use among memory-care RC/AL residents. These findings suggest that memory care may attract residents closer to the end of life and/or promote hospice use at the end of life.}, } @article {pmid38565306, year = {2024}, author = {Zhang, Y and Li, J and Guo, K and Wang, T and Gao, L and Sun, Z and Ma, C and Wang, C and Tian, Y and Zheng, X}, title = {Strigolactones alleviate AlCl3 stress by vacuolar compartmentalization and cell wall blocking in apple.}, journal = {The Plant journal : for cell and molecular biology}, volume = {119}, number = {1}, pages = {197-217}, doi = {10.1111/tpj.16753}, pmid = {38565306}, issn = {1365-313X}, support = {//Breeding Plan of Shandong Provincial Qingchuang Research Team/ ; SDAIT-06-06//Modern Agricultural Technology Industry System of Shandong province/ ; 32001336//National Natural Science Foundation of China/ ; 32102351//National Natural Science Foundation of China/ ; 32172542//National Natural Science Foundation of China/ ; 32372674//National Natural Science Foundation of China/ ; }, mesh = {*Malus/genetics/metabolism/drug effects ; *Vacuoles/metabolism ; *Cell Wall/metabolism/drug effects ; *Aluminum Chloride ; *Plant Proteins/genetics/metabolism ; *Gene Expression Regulation, Plant/drug effects ; Lactones/metabolism/pharmacology ; Plants, Genetically Modified ; Stress, Physiological ; Plant Roots/metabolism/genetics/drug effects ; Heterocyclic Compounds, 3-Ring/metabolism/pharmacology ; Transcription Factors/metabolism/genetics ; Promoter Regions, Genetic ; }, abstract = {Poor management and excess fertilization of apple (Malus domestica Borkh.) orchards are causing increasingly serious soil acidification, resulting in Al toxicity and direct poisoning of roots. Strigolactones (SLs) are reported to be involved in plant responses to abiotic stress, but their role and mechanism under AlCl3 stress remain unknown. Here, we found that applying 1 μm GR24 (an SL analoge) significantly alleviated AlCl3 stress of M26 apple rootstock, mainly by blocking the movement of Al through cell wall and by vacuolar compartmentalization of Al. RNA-seq analysis identified the core transcription factor gene MdWRKY53, and overexpressing MdWRKY53 enhanced AlCl3 tolerance in transgenic apple plants through the same mechanism as GR24. Subsequently, we identified MdPMEI45 (encoding pectin methylesterase inhibitor) and MdALS3 (encoding an Al transporter) as downstream target genes of MdWRKY53 using chromatin immunoprecipitation followed by sequencing (ChIP-seq). GR24 enhanced the interaction between MdWRKY53 and the transcription factor MdTCP15, further increasing the binding of MdWRKY53 to the MdPMEI45 promoter and inducing MdPMEI45 expression to prevent Al from crossing cell wall. MdWRKY53 also bound to the promoter of MdALS3 and enhanced its transcription to compartmentalize Al in vacuoles under AlCl3 stress. We therefore identified two modules involved in alleviating AlCl3 stress in woody plant apple: the SL-WRKY+TCP-PMEI module required for excluding external Al by blocking the entry of Al[3+] into cells and the SL-WRKY-ALS module allowing internal detoxification of Al through vacuolar compartmentalization. These findings lay a foundation for the practical application of SLs in agriculture.}, } @article {pmid38565200, year = {2024}, author = {Stierwalt, J and Stierwalt, JAG and Clark, H and Burda, A and Benavidez Kiley, H and Collins, E and Kortemeyer, M and Miller, E and Peckenschneider, G and Schieltz, E and Shah, Y and Simon, K}, title = {Factors Affecting Performance on a Screening Tool in Persons with Amyotrophic Lateral Sclerosis.}, journal = {Seminars in speech and language}, volume = {45}, number = {3}, pages = {228-241}, doi = {10.1055/s-0044-1785447}, pmid = {38565200}, issn = {1098-9056}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/complications ; Male ; Female ; Middle Aged ; Aged ; Retrospective Studies ; Cognitive Dysfunction/diagnosis ; Neuropsychological Tests ; Frontotemporal Dementia/diagnosis/psychology ; Adult ; Aged, 80 and over ; }, abstract = {Persons with amyotrophic lateral sclerosis (PALS) are at risk of developing cognitive impairments and frontotemporal dementia (FTD). This study examined the relationship between performance of the ALS-Cognitive Behavioral Screen (ALS-CBS) and the demographic parameters of sex, education, time post-ALS diagnosis, and severity of symptoms. Data were collected retrospectively from 69 participants seen at the Mayo Clinic. Correlations were conducted on the ALS-CBS total scores and subsection scores and the above listed parameters; t-tests were conducted between participant subgroups. No statistically significant relationships or differences occurred between the ALS-CBS or its subsections and the variables measured with exception of age and the attention subsection. Older participants had lower ALS-CBS attention subsection scores. Based on the ALS-CBS scores, most participants had some degree of cognitive impairments: 43 had suspected cognitive impairment, 8 had suspected FTD; 18 fell within the normal range of cognitive function. Overall, the variables of sex, education, time post-diagnosis, and severity of symptoms do not appear to influence ALS-CBS scores. It is recommended cognitive screenings be completed for all PALS due to the high risk for developing cognitive impairments and FTD. Such knowledge can help clinicians develop assessment and treatment plans.}, } @article {pmid38564847, year = {2024}, author = {Rajagopalan, V and Pioro, EP}, title = {Differing patterns of cortical grey matter pathology identified by multifractal analysis in UMN-predominant ALS patients with and without corticospinal tract hyperintensity.}, journal = {Journal of the neurological sciences}, volume = {459}, number = {}, pages = {122945}, doi = {10.1016/j.jns.2024.122945}, pmid = {38564847}, issn = {1878-5883}, mesh = {Humans ; *Gray Matter/diagnostic imaging/pathology ; *Amyotrophic Lateral Sclerosis/complications/diagnostic imaging/pathology ; Pyramidal Tracts/diagnostic imaging ; Brain/pathology ; Magnetic Resonance Imaging/methods ; }, abstract = {The pathological hallmarks of amyotrophic lateral sclerosis (ALS) are degeneration of the primary motor cortex grey matter (GM) and corticospinal tract (CST) resulting in upper motor neuron (UMN) dysfunction. Conventional brain magnetic resonance imaging (MRI) shows abnormal CST hyperintensity in some UMN-predominant ALS patients (ALS-CST+) but not in others (ALS-CST-). In addition to the CST differences, we aimed to determine whether GM degeneration differs between ALS-CST+ and ALS-CST- patients by cortical thickness (CT), voxel-based morphometry (VBM) and fractal dimension analyses. We hypothesized that MRI multifractal (MF) measures could differentiate between neurologic controls (n = 14) and UMN-predominant ALS patients as well as between patient subgroups (ALS-CST+, n = 21 vs ALS-CST-, n = 27). No significant differences were observed in CT or GM VBM in any brain regions between patients and controls or between ALS subgroups. MF analyses were performed separately on GM of the whole brain, of frontal, parietal, occipital, and temporal lobes as well as of cerebellum. Estimating MF measures D (Q = 0), D (Q = 1), D (Q = 2), Δf, Δα of frontal lobe GM classified neurologic controls, ALS-CST+ and ALS-CST- groups with 98% accuracy and > 95% in F1, recall, precision and specificity scores. Classification accuracy was only 74% when using whole brain MF measures and < 70% for other brain lobes. We demonstrate that MF analysis can distinguish UMN-predominant ALS subgroups based on GM changes, which the more commonly used quantitative approaches of CT and VBM cannot.}, } @article {pmid38563162, year = {2024}, author = {Pastora, LE and Namburu, NS and Arora, K and Christov, PP and Wilson, JT}, title = {STING-Pathway Inhibiting Nanoparticles (SPINs) as a Platform for Treatment of Inflammatory Diseases.}, journal = {ACS applied bio materials}, volume = {7}, number = {8}, pages = {4867-4878}, pmid = {38563162}, issn = {2576-6422}, support = {T32 DK101003/DK/NIDDK NIH HHS/United States ; P30 DK058404/DK/NIDDK NIH HHS/United States ; }, mesh = {*Membrane Proteins/metabolism/antagonists & inhibitors ; *Nanoparticles/chemistry ; Animals ; Mice ; Inflammation/drug therapy ; Humans ; Biocompatible Materials/chemistry/pharmacology ; Particle Size ; Materials Testing ; Nucleotidyltransferases/antagonists & inhibitors/metabolism ; Signal Transduction/drug effects ; Polylactic Acid-Polyglycolic Acid Copolymer/chemistry ; }, abstract = {Aberrant activation of the cyclic GMP-AMP synthase (cGAS)/Stimulator of Interferon Genes (STING) pathway has been implicated in the development and progression of a myriad of inflammatory diseases including colitis, nonalcoholic steatohepatitis, amyotrophic lateral sclerosis (ALS), and age-related macular degeneration. Thus, STING pathway inhibitors could have therapeutic application in many of these inflammatory conditions. The cGAS inhibitor RU.521 and the STING inhibitor H-151 have shown promise as therapeutics in mouse models of colitis, ALS, and more. However, these agents require frequent high-dose intraperitoneal injections, which may limit translatability. Furthermore, long-term use of systemically administered cGAS/STING inhibitors may leave patients vulnerable to viral infections and cancer. Thus, localized or targeted inhibition of the cGAS/STING pathway may be an attractive, broadly applicable treatment for a variety of STING pathway-driven ailments. Here we describe STING-Pathway Inhibiting Nanoparticles (SPINS)-poly(lactic-co-glycolic acid) (PLGA) nanoparticles loaded with RU.521 and H-151-as a platform for enhanced and sustained inhibition of cGAS/STING signaling. We demonstrate that SPINs are equally or more effective at inhibiting type-I interferon responses induced by cytosolic DNA than free H-151 or RU.521. Additionally, we describe a SPIN formulation in which PLGA is coemulsified with poly(benzoyloxypropyl methacrylamide) (P(HPMA-Bz)), which significantly improves drug loading and allows for tunable release of H-151 over a period of days to over a week by varying P(HPMA-Bz) content. Finally, we find that all SPIN formulations were as potent or more potent in inhibiting cGAS/STING signaling in primary murine macrophages, resulting in decreased expression of inflammatory M1-like macrophage markers. Therefore, our study provides an in vitro proof-of-concept for nanoparticle delivery of STING pathway inhibitors and positions SPINs as a potential platform for slowing or reversing the onset or progression of cGAS/STING-driven inflammatory conditions.}, } @article {pmid38563056, year = {2024}, author = {Umar, TP and Jain, N and Papageorgakopoulou, M and Shaheen, RS and Alsamhori, JF and Muzzamil, M and Kostiks, A}, title = {Artificial intelligence for screening and diagnosis of amyotrophic lateral sclerosis: a systematic review and meta-analysis.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {25}, number = {5-6}, pages = {425-436}, doi = {10.1080/21678421.2024.2334836}, pmid = {38563056}, issn = {2167-9223}, mesh = {*Amyotrophic Lateral Sclerosis/diagnosis/epidemiology ; Humans ; *Artificial Intelligence ; }, abstract = {INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a rare and fatal neurological disease that leads to progressive motor function degeneration. Diagnosing ALS is challenging due to the absence of a specific detection test. The use of artificial intelligence (AI) can assist in the investigation and treatment of ALS.

METHODS: We searched seven databases for literature on the application of AI in the early diagnosis and screening of ALS in humans. The findings were summarized using random-effects summary receiver operating characteristic curve. The risk of bias (RoB) analysis was carried out using QUADAS-2 or QUADAS-C tools.

RESULTS: In the 34 analyzed studies, a meta-prevalence of 47% for ALS was noted. For ALS detection, the pooled sensitivity of AI models was 94.3% (95% CI - 63.2% to 99.4%) with a pooled specificity of 98.9% (95% CI - 92.4% to 99.9%). For ALS classification, the pooled sensitivity of AI models was 90.9% (95% CI - 86.5% to 93.9%) with a pooled specificity of 92.3% (95% CI - 84.8% to 96.3%). Based on type of input for classification, the pooled sensitivity of AI models for gait, electromyography, and magnetic resonance signals was 91.2%, 92.6%, and 82.2%, respectively. The pooled specificity for gait, electromyography, and magnetic resonance signals was 94.1%, 96.5%, and 77.3%, respectively.

CONCLUSIONS: Although AI can play a significant role in the screening and diagnosis of ALS due to its high sensitivities and specificities, concerns remain regarding quality of evidence reported in the literature.}, } @article {pmid38563035, year = {2024}, author = {Fu, Y and Huang, XQ and Qu, HB and Ge, YZ and Ru, XL}, title = {Tandem Mass Tag-Based Proteomic Analysis of Normal and Degenerated Human Intervertebral Discs.}, journal = {Journal of pain research}, volume = {17}, number = {}, pages = {1313-1326}, pmid = {38563035}, issn = {1178-7090}, abstract = {BACKGROUND: Intervertebral disc degeneration (IVDD) is the main cause of low back pain (LBP), but the specific regulatory factors, pathways and specific molecular mechanisms remain unclear.

METHODS: We identified and quantitatively analyzed Pfirrmann Grade II (n=3) and Pfirrmann Grade IV (n=3) pulposus samples via MRI. The differential abundance of proteins in the samples was determined and quantitatively analyzed by relative and absolute quantitative analysis of the isotope marker levels combined with the liquid chromatography-tandem mass spectrometry (LC‒MSMS/MS).

RESULTS: A total of 70 proteins (30 significantly increased proteins (> 1.2-fold change) and 40 significantly decreased proteins (< 0.8-fold change)) showed different levels among the groups. Kyoto Encyclopedia of Genes and Genomes and Gene Ontology (GO) enrichment analyses and Western blot analysis showed that CYCS, RAC1, and PSMD14 may play important roles in IVDD and that Epstein‒Barr virus infection, viral myocarditis, colorectal cancer, nonalcoholic fatty liver disease (NAFLD) and amyotrophic lateral sclerosis (ALS) are the main pathways involved in IVDD.

CONCLUSION: CYCS, RAC1 and PSMD14 may play important roles in IVDD, and Epstein‒Barr virus infection, viral myocarditis, colorectal cancer, NAFLD and ALS may be the main pathways involved in IVDD.}, } @article {pmid38562780, year = {2024}, author = {Krus, KL and Benitez, AM and Strickland, A and Milbrandt, J and Bloom, AJ and DiAntonio, A}, title = {Reduced STMN2 and pathogenic TDP-43, two hallmarks of ALS, synergize to accelerate motor decline in mice.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {38562780}, issn = {2692-8205}, support = {R37 NS065053/NS/NINDS NIH HHS/United States ; R01 NS087632/NS/NINDS NIH HHS/United States ; RF1 AG013730/AG/NIA NIH HHS/United States ; R01 NS119812/NS/NINDS NIH HHS/United States ; UL1 TR002345/TR/NCATS NIH HHS/United States ; }, abstract = {Pathological TDP-43 loss from the nucleus and cytoplasmic aggregation occurs in almost all cases of ALS and half of frontotemporal dementia patients. Stathmin2 (Stmn2) is a key target of TDP-43 regulation and aberrantly spliced Stmn2 mRNA is found in patients with ALS, frontotemporal dementia, and Alzheimer's Disease. STMN2 participates in the axon injury response and its depletion in vivo partially replicates ALS-like symptoms including progressive motor deficits and distal NMJ denervation. The interaction between STMN2 loss and TDP-43 dysfunction has not been studied in mice because TDP-43 regulates human but not murine Stmn2 splicing. Therefore, we generated trans-heterozygous mice that lack one functional copy of Stmn2 and express one mutant TDP-43[Q331K] knock-in allele to investigate whether reduced STMN2 function exacerbates TDP-43-dependent pathology. Indeed, we observe synergy between these two alleles, resulting in an early onset, progressive motor deficit. Surprisingly, this behavioral defect is not accompanied by detectable neuropathology in the brain, spinal cord, peripheral nerves or at neuromuscular junctions (NMJs). However, the trans-heterozygous mice exhibit abnormal mitochondrial morphology in their distal axons and NMJs. As both STMN2 and TDP-43 affect mitochondrial dynamics, and neuronal mitochondrial dysfunction is a cardinal feature of many neurodegenerative diseases, this abnormality likely contributes to the observed motor deficit. These findings demonstrate that partial loss of STMN2 significantly exacerbates TDP-43-associated phenotypes, suggesting that STMN2 restoration could ameliorate TDP-43 related disease before the onset of degeneration.}, } @article {pmid38561605, year = {2024}, author = {Singh, K and Gupta, JK and Kumar, S and Soni, U}, title = {A Review of the Common Neurodegenerative Disorders: Current Therapeutic Approaches and the Potential Role of Bioactive Peptides.}, journal = {Current protein & peptide science}, volume = {25}, number = {7}, pages = {507-526}, pmid = {38561605}, issn = {1875-5550}, mesh = {Humans ; *Neurodegenerative Diseases/drug therapy/metabolism/pathology ; *Peptides/therapeutic use/chemistry/pharmacology ; Animals ; Alzheimer Disease/drug therapy/metabolism/pathology ; Parkinson Disease/drug therapy/metabolism/pathology ; Neuroprotective Agents/therapeutic use/pharmacology/chemistry ; Oxidative Stress/drug effects ; Huntington Disease/drug therapy/metabolism/pathology ; Amyotrophic Lateral Sclerosis/drug therapy/metabolism/pathology ; Cholinesterase Inhibitors/therapeutic use/pharmacology/chemistry ; }, abstract = {Neurodegenerative disorders, which include Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS), represent a significant and growing global health challenge. Current therapies predominantly focus on symptom management rather than altering disease progression. In this review, we discuss the major therapeutic strategies in practice for these disorders, highlighting their limitations. For AD, the mainstay treatments are cholinesterase inhibitors and N-methyl-D-aspartate (NMDA) receptor antagonists. For PD, dopamine replacement therapies, including levodopa, are commonly used. HD is managed primarily with symptomatic treatments, and reusable extends survival in ALS. However, none of these therapies halts or substantially slows the neurodegenerative process. In contrast, this review highlights emerging research into bioactive peptides as potential therapeutic agents. These naturally occurring or synthetically designed molecules can interact with specific cellular targets, potentially modulating disease processes. Preclinical studies suggest that bioactive peptides may mitigate oxidative stress, inflammation, and protein misfolding, which are common pathological features in neurodegenerative diseases. Clinical trials using bioactive peptides for neurodegeneration are limited but show promising initial results. For instance, hemiacetal, a γ-secretase inhibitor peptide, has shown potential in AD by reducing amyloid-beta production, though its development was discontinued due to side effects. Despite these advancements, many challenges remain, including identifying optimal peptides, confirming their mechanisms of action, and overcoming obstacles related to their delivery to the brain. Future research should prioritize the discovery and development of novel bioactive peptides and improve our understanding of their pharmacokinetics and pharmacodynamics. Ultimately, this approach may lead to more effective therapies for neurodegenerative disorders, moving beyond symptom management to potentially modify the course of these devastating diseases.}, } @article {pmid38561079, year = {2024}, author = {Liu, X and Yu, Y and Garcia, LA and Au, ML and Tran, M and Zhang, J and Lou, A and Liu, Y and Wu, H}, title = {A grape-supplemented diet prevented ultraviolet (UV) radiation-induced cataract by regulating Nrf2 and XIAP pathways.}, journal = {The Journal of nutritional biochemistry}, volume = {129}, number = {}, pages = {109636}, pmid = {38561079}, issn = {1873-4847}, support = {R21 EY033941/EY/NEI NIH HHS/United States ; R25 HL125447/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; Mice ; Anthocyanins/pharmacology ; *Cataract/prevention & control/metabolism/etiology ; *Dietary Supplements ; Glutathione/metabolism ; Lens, Crystalline/metabolism/radiation effects/drug effects ; Mice, Inbred C57BL ; *NF-E2-Related Factor 2/metabolism ; Resveratrol/pharmacology ; Signal Transduction/drug effects ; *Ultraviolet Rays/adverse effects ; *Vitis/chemistry ; *X-Linked Inhibitor of Apoptosis Protein/metabolism ; }, abstract = {The purpose of this study is to investigate if grape consumption, in the form of grape powder (GP), could protect against ultraviolet (UV)-induced cataract. Mice were fed with the regular diet, sugar placebo diet, or a grape diet (regular diet supplemented with 5%, 10%, and 15% GP) for 3 months. The mice were then exposed to UV radiation to induce cataract. The results showed that the GP diet dose-dependently inhibited UV-induced cataract and preserved glutathione pools. Interestingly, UV-induced Nrf2 activation was abolished in the groups on the GP diet, suggesting GP consumption may improve redox homeostasis in the lens, making Nrf2 activation unnecessary. For molecular target prediction, a total of 471 proteins regulated by GP were identified using Agilent Literature Search (ALS) software. Among these targets, the X-linked inhibitor of apoptosis (XIAP) was correlated with all of the main active ingredients of GP, including resveratrol, catechin, quercetin, and anthocyanins. Our data confirmed that GP prevented UV-induced suppression of XIAP, indicating that XIAP might be one of the critical molecular targets of GP. In conclusion, this study demonstrated that GP protected the lens from UV-induced cataract development in mice. The protective effects of GP may be attributed to its ability to improve redox homeostasis and activate the XIAP-mediated antiapoptotic pathway.}, } @article {pmid38560980, year = {2024}, author = {Xiang, SR and Ma, Q and Dong, J and Ren, YF and Lin, JZ and Zheng, C and Xiao, P and You, FM}, title = {Contrasting Effects of Music Therapy and Aromatherapy on Perioperative Anxiety: A Systematic Review and Meta-Analysis.}, journal = {Complementary medicine research}, volume = {31}, number = {3}, pages = {278-291}, doi = {10.1159/000538425}, pmid = {38560980}, issn = {2504-2106}, mesh = {*Aromatherapy ; *Music Therapy ; Humans ; *Anxiety/therapy ; Heart Rate ; }, abstract = {INTRODUCTION: Music therapy and aromatherapy have been demonstrated effective for perioperative anxiety. However, the available studies have indicated discordant results about which adjunct treatment is better for perioperative anxiety. Therefore, we conducted this meta-analysis to explore the contrasting effects between them.

METHODS: Six electronic databases were searched for clinical trials evaluating the efficacy of music therapy compared with aromatherapy in alleviating perioperative anxiety. The primary outcome was the postintervention anxiety level. Secondary outcomes included differences in blood pressure and heart rate before and after the intervention as well as pain scores at intraoperative and postoperative time points. The study protocol was registered on PROSPERO (CRD42021249737).

RESULTS: Twelve studies (894 patients) were included. The anxiety level showed no statistically significant difference (SMD, 0.28; 95% CI: -0.12, 0.68; p = 0.17). The analysis of blood pressure and heart rate also did not identify statistically significant differences. Notably, the pain scores at the intraoperative time point suggested that aromatherapy was superior to music therapy (WMD, 0.29 cm; 95% CI: 0.05, 0.52; p = 0.02), while those at 4 h after surgery indicated the opposite results (WMD, -0.48 cm; 95% CI: -0.60, -0.36; p < 0.001).

CONCLUSION: Low-to-moderate quality evidence suggests that music therapy and aromatherapy have similar potential to relieve perioperative anxiety. The potential data indicate that the two therapies have different benefits in intervention duration and age distribution. More direct high-quality comparisons are encouraged in the future to verify this point.

UNLABELLED: EinleitungMusik- und Aromatherapie haben sich bei perioperativen Angstzuständen als wirksam erwiesen. Die verfügbaren Studien zeigten jedoch widersprüchliche Ergebnisse zur Frage, welche adjuvante Therapie bei perioperativen Angstzuständen besser ist. Daher führten wir die vorliegende Metaanalyse durch, um die unterschiedlichen Effekte der beiden Therapien zu untersuchen.MethodenSechs (6) elektronische Datenbanken wurden nach klinischen Studien zur Wirksamkeit von Musiktherapie im Vergleich zur Aromatherapie bei der Linderung perioperativer Angstzustände durchsucht. Primäres Zielkriterium war das Angstniveau nach der Intervention. Die sekundären Zielkriterien umfassten die Unterschiede bei Blutdruck und Herzfrequenz vor und nach der Intervention sowie die Schmerz-Scores zu intra- und postoperativen Zeitpunkten. Das Studienprotokoll wurde auf PROSPERO (CRD42021249737) registriert.ErgebnisseZwölf (12) Studien (894 Patienten) wurden eingeschlossen. Das Angstniveau zeigte keinen statistisch signifikanten Unterschied (SMD, 0,28; 95%-KI: −0,12, 0,68, p = 0,17) und auch die Analyse von Blutdruck und Herzfrequenz ergab keine statistisch signifikanten Unterschiede. Insbesondere die Schmerz-Scores zum intraoperativen Zeitpunkt sprachen dafür, dass die Aromatherapie gegenüber der Musiktherapie überlegen war (WMD, 0,29 cm; 95%-KI: 0,05, 0,52; p = 0,02), während die Werte 4 Stunden nach der Operation gegenteilige Ergebnisse zeigten (WMD, −0,48 cm; 95%-KI: −0,60, −0,36, p < 0,001).SchlussfolgerungEvidenzen von geringer bis mässiger Qualität deuten darauf hin, dass Musik- und Aromatherapie ein vergleichbares Potenzial bei der Linderung perioperativer Ängste besitzen. Die potenziellen Daten zeigen, dass die beiden Therapien unterschiedliche Vorteile hinsichtlich Interventionsdauer und Altersverteilung haben. Künftig sollten mehr direkte und qualitativ hochwertige Vergleiche durchgeführt werden, um diesen Aspekt zu überprüfen.}, } @article {pmid38560897, year = {2024}, author = {Minatoguchi, S and Fujita, Y and Niizuma, K and Tominaga, T and Yamashita, T and Abe, K and Dezawa, M}, title = {Donor Muse Cell Treatment Without HLA-Matching Tests and Immunosuppressant Treatment.}, journal = {Stem cells translational medicine}, volume = {13}, number = {6}, pages = {532-545}, pmid = {38560897}, issn = {2157-6580}, support = {//New Energy and Industrial Technology Development Organization/ ; //Japan Agency for Medical Research and Development/ ; //Ministry of Education, Culture, Sports, Science and Technology/ ; //Japan Society for the Promotion of Science/ ; //SENSHIN Medical Research Foundation/ ; //Life Science Institute Inc/ ; }, mesh = {Humans ; *Mesenchymal Stem Cells/cytology/metabolism ; Mesenchymal Stem Cell Transplantation/methods ; Immunosuppressive Agents/pharmacology/therapeutic use ; HLA Antigens/metabolism ; Cell Differentiation ; Animals ; Histocompatibility Testing/methods ; }, abstract = {The strength of stem cell therapy is the regeneration of tissues by synergistic pleiotropic effects. Among many stem cell types, mesenchymal stem cells (MSCs) that are comprised of heterogenous population are widely used for clinical applications with the expectation of pleiotropic bystander effects. Muse cells are pluripotent-like/macrophage-like stem cells distributed in the bone marrow, peripheral blood, and organ connective tissues as cells positive for the pluripotent surface marker stage-specific-embryonic antigen -3. Muse cells comprise ~1% to several percent of MSCs. While Muse cells and MSCs share several characteristics, such as mesenchymal surface marker expression and their bystander effects, Muse cells exhibit unique characteristics not observed in MSCs. These unique characteristics of Muse cells include selective homing to damaged tissue after intravenous injection rather than being trapped in the lung like MSCs, replacement of a wide range of damaged/apoptotic cells by differentiation through phagocytosis, and long-lasting immunotolerance for donor cell use. In this review, we focus on the basic properties of Muse cells clarified through preclinical studies and clinical trials conducted by intravenous injection of donor-Muse cells without HLA-matching tests or immunosuppressant treatment. MSCs are considered to differentiate into osteogenic, chondrogenic, and adipogenic cells, whereas the range of their differentiation has long been debated. Muse cells may provide clues to the wide-ranging differentiation potential of MSCs that are observed with low frequency. Furthermore, the utilization of Muse cells may provide a novel strategy for clinical treatment.}, } @article {pmid38559706, year = {2024}, author = {Bhor, S and Tonny, SH and Dinesh, S and Sharma, S}, title = {Computational screening of damaging nsSNPs in human SOD1 genes associated with amyotrophic lateral sclerosis identifies destabilising effects of G38R and G42D mutations through in silico evaluation.}, journal = {In silico pharmacology}, volume = {12}, number = {1}, pages = {20}, pmid = {38559706}, issn = {2193-9616}, abstract = {Amyotrophic lateral sclerosis (ALS), a complicated neurodegenerative disorder affected by hereditary and environmental variables, is a condition. In this study, the genetic makeup of ALS is investigated, with a focus on the SOD1 gene's single-nucleotide polymorphisms (SNPs) and their ability to affect disease risk. Eleven high-risk missense variations that may impair the functionality of the SOD1 protein were discovered after a thorough examination of SNPs in the SOD1 gene. These mutations were chosen using a variety of prediction approaches, highlighting their importance in the aetiology of ALS. Notably, it was discovered that the stability of the SOD1 wild-type protein structure was compromised by the G38R and G42D SOD1 variants. Additionally, Edaravone, a possible ALS medication, showed a greater affinity for binding mutant SOD1 structures, pointing to potential personalised treatment possibilities. The high-risk SNPs discovered in this investigation seem to have functional effects, especially on the stability of proteins and their interactions with other molecules. This study clarifies the complex genetics of ALS and offers insights into how these genetic variations may affect the effectiveness of therapeutic interventions, particularly in the context of edaravone. In this study advances our knowledge of the genetic mechanisms causing ALS vulnerability and prospective therapeutic strategies. Future studies are necessary to confirm these results and close the gap between individualised clinical applications and improved ALS care.}, } @article {pmid38559165, year = {2024}, author = {Sirtori, R and Gregoire, M and Potts, E and Collins, A and Donatelli, L and Fallini, C}, title = {LINC complex alterations are a hallmark of sporadic and familial ALS/FTD.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2024.03.08.584123}, pmid = {38559165}, issn = {2692-8205}, support = {P20 GM103430/GM/NIGMS NIH HHS/United States ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder that primarily affects motor neurons, leading to progressive muscle weakness and loss of voluntary muscle control. While the exact cause of ALS is not fully understood, emerging research suggests that dysfunction of the nuclear envelope (NE) may contribute to disease pathogenesis and progression. The NE plays a role in ALS through several mechanisms, including nuclear pore defects, nucleocytoplasmic transport impairment, accumulation of mislocalized proteins, and nuclear morphology abnormalities. The LINC complex is the second biggest multi-protein complex in the NE and consists of the SUN1/2 proteins spanning the inner nuclear membrane and Nesprin proteins embedded in the outer membrane. The LINC complex, by interacting with both the nuclear lamina and the cytoskeleton, transmits mechanical forces to the nucleus regulating its morphology and functional homeostasis. In this study we show extensive alterations to the LINC complex in motor and cortical iPSC-derived neurons and spinal cord organoids carrying the ALS causative mutation in the C9ORF72 gene (C9). Importantly, we show that such alterations are present in vivo in a cohort of sporadic ALS and C9-ALS postmortem spinal cord and motor cortex biopsies. We also found that LINC complex disruption strongly correlated with nuclear morphological alterations occurring in ALS neurons, independently of TDP43 mislocalization. Altogether, our data establish morphological and functional alterations to the LINC complex as important events in ALS pathogenic cascade, making this pathway a possible target for both biomarker and therapy development.}, } @article {pmid38558260, year = {2024}, author = {Fonteh, CN and Patnaik, JL and Grove, NC and Lynch, AM and Pantcheva, MB and Christopher, KL}, title = {Refractive outcomes using Barrett formulas and patient characteristics of cataract surgery patients with and without prior LASIK/PRK.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {262}, number = {9}, pages = {2937-2944}, pmid = {38558260}, issn = {1435-702X}, mesh = {Humans ; Retrospective Studies ; Female ; Male ; *Photorefractive Keratectomy/methods ; *Visual Acuity/physiology ; *Refraction, Ocular/physiology ; *Keratomileusis, Laser In Situ/methods ; Aged ; *Lasers, Excimer/therapeutic use ; Middle Aged ; Cataract Extraction/methods ; Follow-Up Studies ; Refractive Errors/physiopathology/diagnosis ; Treatment Outcome ; Myopia/surgery/physiopathology ; Axial Length, Eye/pathology ; }, abstract = {PURPOSE: The goal of this study is to describe characteristics of cataract surgery patients who previously underwent laser in situ keratomileusis/photorefractive keratectomy (LASIK/PRK) in comparison to non-LASIK/PRK cataract surgery patients including psychiatric comorbidities, as well as describe refractive prediction error after cataract surgery while accounting for axial length (AL) using the Barrett True-K and Barrett Universal II formulas.

METHODS: This was a retrospective study of patients from the University of Colorado Cataract Outcomes Registry. The primary outcomes were refraction prediction error (RPE), mean absolute RPE, and median absolute RPE. Outcomes were stratified by five axial length groups. Univariate and multivariate models for RPE were stratified by the AL group.

RESULTS: Two hundred eighty-one eyes with prior LASIK/PRK and 3101 eyes without are included in the study. Patients with prior LASIK/PRK were significantly younger: 67.0 vs 69.9 years, p < 0.0001. The LASIK/PRK group had significantly better mean pre-operative BCVA in comparison to the non-LASIK group, logMAR 0.204 vs logMAR 0.288, p = 0.003. The LASIK/PRK group had significantly lower rates of cardiovascular disease (18.5% vs 29.3%, p < 0.001), hypertension (49.1% vs 59.3%, p < 0.012), and type 2 diabetes (10.7% vs 26.0%, p < 0.001), and no significant difference in psychiatric disease. The absolute RPE was higher for the LASIK group for all ALs, but only significantly higher for eyes with AL less than 25 mm.

CONCLUSION: Patient eyes with prior LASIK/PRK surgery undergoing cataract surgery were significantly younger, had significantly less comorbidities, and a significantly better pre-operative BCVA. Using the Barrett formulas, absolute prediction error for eyes with longer ALs was not significantly worse for LASIK/PRK eyes than those without and the difference was smaller for eyes with longer AL.}, } @article {pmid38558150, year = {2024}, author = {Pensato, U and Cortelli, P}, title = {Soccer (football) and brain health.}, journal = {Journal of neurology}, volume = {271}, number = {6}, pages = {3019-3029}, pmid = {38558150}, issn = {1432-1459}, mesh = {Humans ; *Soccer/injuries ; *Brain Concussion/complications/epidemiology/etiology ; Athletic Injuries/complications ; Brain/physiopathology ; Chronic Traumatic Encephalopathy/etiology ; }, abstract = {Soccer is one of the most popular sports worldwide, played by over 270 million people and followed by many more. Several brain health benefits are promoted by practising soccer and physical exercise at large, which helps contrast the cognitive decline associated with ageing by enhancing neurogenesis processes. However, sport-related concussions have been increasingly recognised as a pressing public health concern, not only due to their acute impact but also, more importantly, due to mounting evidence indicating an elevated risk for the development of neurological sequelae following recurrent head traumas, especially chronic traumatic encephalopathy (CTE). While soccer players experience less frequent concussions compared with other contact or combat sports, such as American football or boxing, it stands alone in its purposeful use of the head to hit the ball (headings), setting its players apart as the only athletes exposed to intentional, sub-concussive head impacts. Additionally, an association between soccer and amyotrophic lateral sclerosis has been consistently observed, suggesting a potential "soccer-specific" risk factor. In this review, we discuss the neurological sequelae related to soccer playing, the emerging evidence of a detrimental effect related to recurrent headings, and the need for implementation of comprehensive strategies aimed at preventing and managing the burden of head impact in soccer.}, } @article {pmid38557405, year = {2024}, author = {Goutman, SA and Boss, J and Jang, DG and Piecuch, C and Farid, H and Batra, M and Mukherjee, B and Feldman, EL and Batterman, SA}, title = {Residential exposure associations with ALS risk, survival, and phenotype: a Michigan-based case-control study.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {25}, number = {5-6}, pages = {543-553}, pmid = {38557405}, issn = {2167-9223}, support = {K23 ES027221/ES/NIEHS NIH HHS/United States ; R01 ES030049/ES/NIEHS NIH HHS/United States ; P30 ES017885/ES/NIEHS NIH HHS/United States ; UL1 TR002240/TR/NCATS NIH HHS/United States ; R01 NS127188/NS/NINDS NIH HHS/United States ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/epidemiology/mortality ; Female ; Male ; Michigan/epidemiology ; Case-Control Studies ; *Environmental Exposure/adverse effects/statistics & numerical data ; Middle Aged ; Aged ; Risk Factors ; *Phenotype ; Adult ; }, abstract = {BACKGROUND: Environmental exposures impact amyotrophic lateral sclerosis (ALS) risk and progression, a fatal and progressive neurodegenerative disease. Better characterization of these exposures is needed to decrease disease burden.

OBJECTIVE: To identify exposures in the residential setting that associate with ALS risk, survival, and onset segment.

METHODS: ALS and control participants recruited from University of Michigan completed a survey that ascertained exposure risks in the residential setting. ALS risk was assessed using logistic regression models followed by latent profile analysis to consider exposure profiles. A case-only analysis considered the contribution of the residential exposure variables via a Cox proportional hazards model for survival outcomes and multinomial logistic regression for onset segment, a polytomous outcome.

RESULTS: This study included 367 ALS and 255 control participants. Twelve residential variables were associated with ALS risk after correcting for multiple comparison testing, with storage in an attached garage of chemical products including gasoline or kerosene (odds ratio (OR) = 1.14, padjusted < 0.001), gasoline-powered equipment (OR = 1.16, padjusted < 0.001), and lawn care products (OR = 1.15, padjusted < 0.001) representing the top three risk factors sorted by padjusted. Latent profile analysis indicated that storage of these chemical products in both attached and detached garages increased ALS risk. Although residential variables were not associated with poorer ALS survival following multiple testing corrections, storing pesticides, lawn care products, and woodworking supplies in the home were associated with shorter ALS survival using nominal p values. No exposures were associated with ALS onset segment.

CONCLUSION: Residential exposures may be important modifiable components of the ALS susceptibility and prognosis exposome.}, } @article {pmid38557366, year = {2024}, author = {Sopranzi, FM and Faragalli, A and Pompili, M and Carle, F and Gesuita, R and Ceravolo, MG}, title = {Incidence of amyotrophic lateral sclerosis before and during the COVID-19 pandemic: evidence from an 8-year population-based study in Central Italy based on healthcare utilization databases.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {25}, number = {5-6}, pages = {554-562}, doi = {10.1080/21678421.2024.2336127}, pmid = {38557366}, issn = {2167-9223}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/epidemiology/diagnosis ; Italy/epidemiology ; Male ; Female ; Aged ; *COVID-19/epidemiology ; Incidence ; Middle Aged ; Longitudinal Studies ; Databases, Factual ; Aged, 80 and over ; Patient Acceptance of Health Care/statistics & numerical data ; Adult ; SARS-CoV-2 ; Hospitalization/statistics & numerical data ; }, abstract = {BACKGROUND: Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disorder with a high multidimensional burden, with an obscure etiopathogenesis.

METHODS: We designed a longitudinal, population-based study of people residing in Central Italy (Marche Region) who were beneficiaries of the National Health System. People with an unprecedented ALS hospitalization (335.20 ICD-9 CM) or tagged with an ALS exemption between 2014 and 2021 were considered incident cases. ALS cases residing in the region for <3 years or with an active ALS exemption or hospitalized for ALS before 2014 were excluded. We used secondary sources to identify new ALS diagnoses. The regional referral center for ALS's database was used to test the accuracy of secondary sources in detecting cases. ALS mean incidence was compared to that reported in similar studies conducted in Italy. The incidence rate trend adjusted by sex and age was evaluated using the Poisson regression model.

RESULTS: We detected 425 new ALS cases (median age: 70y) in the 2014-2021 period, with a mean incidence of 3.5:100,000 py (95%CI: 3.2-3.8; M:F = 1.2), similar to that reported in similar studies conducted in Italy. No trend was observed during 2014-2019. After including 2020-2021 in the model, we observed a mean decrease in incidence of 5.8% (95% CI 2.0%; 9.5%, p = 0.003).

CONCLUSION: We show a decrease in the incidence rate of ALS in Marche, during the 2014-2021 period, as a possible outcome of a delayed neurological assessment and diagnosis during the pandemic. An ad hoc developed identification algorithm, based on healthcare utilization databases, is a valuable tool to assess the health impact of global contingencies.}, } @article {pmid38556190, year = {2024}, author = {Fu, X and Zhang, Z and Hayes, LR and Wright, N and Asbury, J and Li, S and Ye, Y and Sun, S}, title = {DDX3X overexpression decreases dipeptide repeat proteins in a mouse model of C9ORF72-ALS/FTD.}, journal = {Experimental neurology}, volume = {376}, number = {}, pages = {114768}, pmid = {38556190}, issn = {1090-2430}, support = {R21 AG072078/AG/NIA NIH HHS/United States ; R01 NS123538/NS/NINDS NIH HHS/United States ; R01 NS107347/NS/NINDS NIH HHS/United States ; RF1 NS113820/NS/NINDS NIH HHS/United States ; RF1 NS127925/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Humans ; Male ; Mice ; *Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology ; *C9orf72 Protein/genetics/metabolism ; *DEAD-box RNA Helicases/genetics/metabolism ; Dipeptides/metabolism ; *Disease Models, Animal ; DNA Repeat Expansion/genetics ; *Frontotemporal Dementia/genetics/metabolism/pathology ; Mice, Transgenic ; }, abstract = {Hexanucleotide repeat expansion in C9ORF72 (C9) is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). One of the proposed pathogenic mechanisms is the neurotoxicity arising from dipeptide repeat (DPR) proteins produced by repeat-associated non-AUG (RAN) translation. Therefore, reducing DPR levels emerges as a potential therapeutic strategy for C9ORF72-ALS/FTD. We previously identified an RNA helicase, DEAD-box helicase 3 X-linked (DDX3X), modulates RAN translation. DDX3X overexpression decreases poly-GP accumulation in C9ORF72-ALS/FTD patient-derived induced pluripotent stem cell (iPSC)-differentiated neurons (iPSNs) and reduces the glutamate-induced neurotoxicity. In this study, we examined the in vivo efficacy of DDX3X overexpression using a mouse model. We expressed exogenous DDX3X or GFP in the central nervous system (CNS) of the C9-500 ALS/FTD BAC transgenic or non-transgenic control mice using adeno-associated virus serotype 9 (AAV9). The DPR levels were significantly reduced in the brains of DDX3X-expressing C9-BAC mice compared to the GFP control even twelve months after virus delivery. Additionally, p62 aggregation was also decreased. No neuronal loss or neuroinflammatory response were detected in the DDX3X overexpressing C9-BAC mice. This work demonstrates that DDX3X overexpression effectively reduces DPR levels in vivo without provoking neuroinflammation or neurotoxicity, suggesting the potential of increasing DDX3X expression as a therapeutic strategy for C9ORF72-ALS/FTD.}, } @article {pmid38555304, year = {2024}, author = {Cheng, CJ and Su, JJ}, title = {Detecting muscle-specific kinase myasthenia gravis in atypical presentations.}, journal = {Acta neurologica Belgica}, volume = {124}, number = {5}, pages = {1733-1735}, pmid = {38555304}, issn = {2240-2993}, } @article {pmid38554281, year = {2024}, author = {Dermentzaki, G and Furlan, M and Tanaka, I and Leonardi, T and Rinchetti, P and Passos, PMS and Bastos, A and Ayala, YM and Hanna, JH and Przedborski, S and Bonanomi, D and Pelizzola, M and Lotti, F}, title = {Depletion of Mettl3 in cholinergic neurons causes adult-onset neuromuscular degeneration.}, journal = {Cell reports}, volume = {43}, number = {4}, pages = {113999}, pmid = {38554281}, issn = {2211-1247}, support = {R01 AG084965/AG/NIA NIH HHS/United States ; }, mesh = {Animals ; Humans ; Mice ; Adenosine/metabolism/analogs & derivatives ; Amyotrophic Lateral Sclerosis/metabolism/pathology/genetics ; *Cholinergic Neurons/metabolism/pathology ; DNA-Binding Proteins/metabolism/genetics ; *Methyltransferases/metabolism/genetics ; Motor Neurons/metabolism/pathology ; *Neuromuscular Diseases/metabolism/pathology ; }, abstract = {Motor neuron (MN) demise is a hallmark of several neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). Post-transcriptional gene regulation can control RNA's fate, and defects in RNA processing are critical determinants of MN degeneration. N[6]-methyladenosine (m[6]A) is a post-transcriptional RNA modification that controls diverse aspects of RNA metabolism. To assess the m[6]A requirement in MNs, we depleted the m[6]A methyltransferase-like 3 (METTL3) in cells and mice. METTL3 depletion in embryonic stem cell-derived MNs has profound and selective effects on survival and neurite outgrowth. Mice with cholinergic neuron-specific METTL3 depletion display a progressive decline in motor behavior, accompanied by MN loss and muscle denervation, culminating in paralysis and death. Reader proteins convey m[6]A effects, and their silencing phenocopies METTL3 depletion. Among the m[6]A targets, we identified transactive response DNA-binding protein 43 (TDP-43) and discovered that its expression is under epitranscriptomic control. Thus, impaired m[6]A signaling disrupts MN homeostasis and triggers neurodegeneration conceivably through TDP-43 deregulation.}, } @article {pmid38554151, year = {2024}, author = {Campos-Díaz, A and Morejón-García, P and Monte-Serrano, E and Ros-Pardo, D and Marcos-Alcalde, I and Gómez-Puertas, P and Lazo, PA}, title = {Pathogenic effects of Leu200Pro and Arg387His VRK1 protein variants on phosphorylation targets and H4K16 acetylation in distal hereditary motor neuropathy.}, journal = {Journal of molecular medicine (Berlin, Germany)}, volume = {102}, number = {6}, pages = {801-817}, pmid = {38554151}, issn = {1432-1440}, support = {PID2019-105610RB-I00//Agencia Estatal de Investigación/ ; PID2022-139598OB-I00//Agencia Estatal de Investigación/ ; RED2018-102801-T//Agencia Estatal de Investigación/ ; RTC-2017-6494-1//Agencia Estatal de Investigación/ ; RTI2018-094434-B-I00//Agencia Estatal de Investigación/ ; CSI264P20//Consejería de Educación, Junta de Castilla y León/ ; CLC-2017-01//Consejería de Educación, Junta de Castilla y León/ ; CSI004-18//Consejería de Educación, Junta de Castilla y León/ ; FPU20/02978//Ministerio de Universidades/ ; FPU16/01883//Ministerio de Universidades/ ; }, mesh = {Humans ; Acetylation ; *Histones/metabolism ; Phosphorylation ; *Protein Serine-Threonine Kinases/metabolism/genetics ; *Intracellular Signaling Peptides and Proteins/genetics/metabolism ; Male ; Female ; DNA-Binding Proteins/genetics/metabolism ; Middle Aged ; Motor Neuron Disease/genetics/metabolism ; Nuclear Proteins/genetics/metabolism ; }, abstract = {Rare recessive variants in the human VRK1 gene are associated with several motor neuron diseases (MND), such as amyotrophic lateral sclerosis, spinal muscular atrophy, or distal hereditary motor neuropathies (dHMN). A case with dHMN carrying two novel VRK1 gene variants, expressing Leu200Pro (L200P) and Arg387His (R387H) variant proteins, identified that these protein variants are functionally different. The Leu200Pro variant shares with several variants in the catalytic domain the loss of the kinase activity on different substrates, such as histones, p53, or coilin. However, the distal Arg387His variant and the distal Trp375* (W375X) chinese variant, both located at the end of the low complexity C-terminal region and proximal to the termination codon, retain their catalytic activity on some substrates, and mechanistically their functional impairment is different. The L200P variant, as well as most VRK1 pathogenic variants, impairs the phosphorylation of BAF and histone H4K16 acetylation, which are required for DNA attachment to the nuclear envelope and chromatin accessibility to DNA repair mechanisms, respectively. The R387H variant impairs phosphorylation of H2AX, an early step in different types of DNA damage responses. The functional variability of VRK1 protein variants and their different combinations are a likely contributor to the clinical phenotypic heterogeneity of motor neuron and neurological diseases associated with rare VRK1 pathogenic variants. KEY MESSAGES: VRK1 variants implicated in motor neuron diseases are functionally different. The L200P variant is kinase inactive, and the R387H variant is partially active. VRK1 variants alter H4K16 acetylation and loss of coilin and BAF phosphorylation. VRK1 variants alter Cajal bodies and DNA damage responses. VRK1 variant combination determines the neurological phenotype heterogeneity.}, } @article {pmid38553272, year = {2024}, author = {Desmaison, A and Truffert, A and Pereira, B and Camdessanché, JP and Moisset, X and Guy, N}, title = {Upper motor neuron assessment in amyotrophic lateral sclerosis using the patellar tendon reflex and motor-evoked potentials to the lower limbs.}, journal = {Revue neurologique}, volume = {180}, number = {7}, pages = {632-641}, doi = {10.1016/j.neurol.2024.01.006}, pmid = {38553272}, issn = {0035-3787}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/physiopathology/pathology ; Male ; Middle Aged ; Female ; Aged ; *Evoked Potentials, Motor/physiology ; *Motor Neurons/physiology ; Adult ; *Lower Extremity/physiopathology ; Electromyography/methods ; Reflex, Stretch/physiology ; Aged, 80 and over ; Sensitivity and Specificity ; Reflex/physiology ; }, abstract = {Amyotrophic lateral sclerosis (ALS) diagnosis relies on signs of progressive damage to both lower motoneuron (LMN), given by clinical examination and electromyography (EMG), and upper motoneuron (UMN), given by clinical examination only. Recognition of UMN involvement, however, is still difficult, so that diagnostic delay often remains too long. Shortening the time to clinical and genetic diagnosis is essential in order to provide accurate information to patients and families, avoid time-consuming investigations and for appropriate care management. This study investigates whether combined patellar tendon reflex recording with motor-evoked potentials to the lower limbs (T-MEP-LL) is relevant to assess corticospinal function in ALS, so that it might serve as a tool improving diagnosis. T-MEP-LL were recorded in 135 patients with suspected motor neuron disease (MND) from February 2010 to March 2021. The sensitivity, specificity, and ability to improve diagnosis when added to Awaji and Gold Coast criteria were determined. The main finding of the study is that T-MEP-LL can detect UMN dysfunction with a 70% sensitivity and 63% specificity when UMN clinical signs are lacking. The sensitivity reaches 82% when considering all MND patients. Moreover, at first evaluation, using T-MEP-LL to quantify reflex briskness and to measure central conduction time, can improve the diagnostic accuracy. T-MEP-LL is easy to perform and does not need any electrical stimulation, making the test rapid, and painless. By the simultaneous quantification of both UMN and LMN system, it could also help to identify different phenotype with more accuracy than clinical examination in this broad-spectrum pathology. The question whether T-MEP-LL could further be a real biomarker need further prospective studies.}, } @article {pmid38552851, year = {2024}, author = {Yang, L and Guttman, L and Dawson, VL and Dawson, TM}, title = {Parthanatos: Mechanisms, modulation, and therapeutic prospects in neurodegenerative disease and stroke.}, journal = {Biochemical pharmacology}, volume = {228}, number = {}, pages = {116174}, pmid = {38552851}, issn = {1873-2968}, support = {R01 AG085688/AG/NIA NIH HHS/United States ; R01 NS067525/NS/NINDS NIH HHS/United States ; }, mesh = {Humans ; *Neurodegenerative Diseases/drug therapy/metabolism ; Animals ; *Stroke/drug therapy/metabolism/therapy ; *Parthanatos/drug effects/physiology ; Neuroprotective Agents/therapeutic use ; }, abstract = {Parthanatos is a cell death signaling pathway that has emerged as a compelling target for pharmaceutical intervention. It plays a pivotal role in the neuron loss and neuroinflammation that occurs in Parkinson's Disease (PD), Alzheimer's Disease (AD), Huntington's Disease (HD), Amyotrophic Lateral Sclerosis (ALS), and stroke. There are currently no treatments available to humans to prevent cell death in any of these diseases. This review provides an in-depth examination of the current understanding of the Parthanatos mechanism, with a particular focus on its implications in neuroinflammation and various diseases discussed herein. Furthermore, we thoroughly review potential intervention targets within the Parthanatos pathway. We dissect recent progress in inhibitory strategies, complimented by a detailed structural analysis of key Parthanatos executioners, PARP-1, AIF, and MIF, along with an assessment of their established inhibitors. We hope to introduce a new perspective on the feasibility of targeting components within the Parthanatos pathway, emphasizing its potential to bring about transformative outcomes in therapeutic interventions. By delineating therapeutic opportunities and known targets, we seek to emphasize the imperative of blocking Parthanatos as a precursor to developing disease-modifying treatments. This comprehensive exploration aims to catalyze a paradigm shift in our understanding of potential neurodegenerative disease therapeutics, advocating for the pursuit of effective interventions centered around Parthanatos inhibition.}, } @article {pmid38552475, year = {2024}, author = {Offroy, M and Marchetti, M and Kauffmann, TH and Bourson, P and Duponchel, L and Savarese, L and Mechling, JM}, title = {Using clustering as pre-processing in the framework of signal unmixing for exhaustive exploration of archaeological artefacts in Raman imaging.}, journal = {Talanta}, volume = {274}, number = {}, pages = {125955}, doi = {10.1016/j.talanta.2024.125955}, pmid = {38552475}, issn = {1873-3573}, abstract = {Analytical chemistry on archaeological material is an essential part of modern archaeological investigations and from year to year, instrumental improvement has made it possible to generate data at a high spatial and temporal frequency. In particular, Raman spectral imaging can be successfully applied in archaeological research by its simplicity of implementation to study past human societies through the analysis of their material remains. This technique makes it possible to simultaneously obtain spatial and spectral information by preserving sample integrity. However, because of the inherent complexity of the samples in Archaeology (e.g. seniority, fragility, lack or full absence of any information about its composition), chemical interpretation can be difficult at first glance. Indeed, specific problems of spectral selectivity related to unexpected chemical compounds could appear due to their state of conservation. Furthermore, detecting minor compounds becomes challenging as major components impose their contributions in the acquired spectra. Therefore, a relevant chemometric approach has been introduced in this context to characterize distinct spectral sources in a Raman imaging dataset of an archaeological specimen - a mosaic fragment. The fragment was unearthed during the Ruscino archaeological dig on the outskirts of Perpignan, France. It dates back to the oppidum period. The aim is to extract selective spectral information from pixel clustering analysis in order to enhance the initial optimisation step within the Multivariate Curve Resolution and Alternating Least-Squares (MCR-ALS) algorithm, a well-known signal unmixing technique. The underlying principle of the MCR-ALS is that the acquired spectra can be expressed as linear combinations of pure spectra of all individual components present in the chemical system under study. Sometimes it can be difficult to obtain the desired results through the algorithm, particularly if initial estimates of spectral or concentration profiles are inaccurate due to complex signals, noise or lack of selectivity, resulting in rank deficiency (i.e. a poor estimation of the total number of pure signals). For this reason, an innovative threshold-based clustering algorithm, combined with multiple Orthogonal Projection Approaches (OPA), has been developed to improve matrix rank investigation and thus the initialisation step of the MCR-ALS approach before optimisation. The effective analysis of Raman imaging data for an archaeological mosaic played a crucial role in uncovering significant chemical information about a particular biogenic material. This insight sheds light on the origins of mortar manufacture during the oppidum period.}, } @article {pmid38552376, year = {2024}, author = {Donayeva, A and Abdelazim, IA and Amanzholkyzy, A}, title = {Regarding cornual pregnancy as a rare entity of ectopic pregnancy: A case report.}, journal = {International journal of surgery case reports}, volume = {118}, number = {}, pages = {109574}, pmid = {38552376}, issn = {2210-2612}, abstract = {The published Toumi et al's article is somewhat confusing to the readers. The cornual pregnancy (CP) defined as a pregnancy that occurs in a rudimentary horn of a uterus with a Müllerian anomaly according to William's textbook. The interstitial ectopic pregnancy (IEP) occurs in the interstitial part of the fallopian tube where it crosses the uterine muscular to enter the uterine cavity. The IEP sonographic findings include an empty uterus with an eccentrically placed gestational sac, located ≥1 cm from the endometrial margin and bordered by ≤ 5 mm myometrial rim.}, } @article {pmid38551974, year = {2024}, author = {Jiménez-García, AM and Bonnel, G and Álvarez-Mota, A and Arias, N}, title = {Current perspectives on neuromodulation in ALS patients: A systematic review and meta-analysis.}, journal = {PloS one}, volume = {19}, number = {3}, pages = {e0300671}, pmid = {38551974}, issn = {1932-6203}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis ; Quality of Life ; *Neurodegenerative Diseases ; Exercise Therapy/methods ; Muscle Spasticity ; }, abstract = {Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disease that affects motor neurons, resulting in muscle weakness, paralysis, and eventually patient mortality. In recent years, neuromodulation techniques have emerged as promising potential therapeutic approaches to slow disease progression and improve the quality of life of ALS patients. A systematic review was conducted until August 8, 2023, to evaluate the neuromodulation methods used and their potential in the treatment of ALS. The search strategy was applied in the Cochrane Central database, incorporating results from other databases such as PubMed, Embase, CTgov, CINAHL, and ICTRP. Following the exclusion of papers that did not fulfil the inclusion criteria, a total of 2090 records were found, leaving a total of 10 studies. R software was used to conduct meta-analyses based on the effect sizes between the experimental and control groups. This revealed differences in muscle stretch measures with manual muscle testing (p = 0.012) and resting motor threshold (p = 0.0457), but not with voluntary isometric contraction (p = 0.1883). The functionality of ALS was also different (p = 0.007), but not the quality of life. Although intracortical facilitation was not seen in motor cortex 1 (M1) (p = 0.1338), short-interval intracortical inhibition of M1 was significant (p = 0.0001). BDNF showed no differences that were statistically significant (p = 0.2297). Neuromodulation-based treatments are proposed as a promising therapeutic approach for ALS that can produce effects on muscle function, spasticity, and intracortical connections through electrical, magnetic, and photonic stimulation. Photobiomodulation stands out as an innovative approach that uses specific wavelengths to influence mitochondria, with the aim of improving mitochondrial function and reducing excitotoxicity. The lack of reliable placebo controls and the variation in stimulation frequency are some of the drawbacks of neuromodulation.}, } @article {pmid38550565, year = {2024}, author = {Di Nardo, AA and Prochiantz, A}, title = {Therapeutic value of homeoprotein signaling pathways.}, journal = {Frontiers in neuroscience}, volume = {18}, number = {}, pages = {1359523}, pmid = {38550565}, issn = {1662-4548}, abstract = {Cell signaling based on homeoprotein transfer is a pathway with developmental and physiological functions. For a few transcription factors of this family, primarily ENGRAILED1, ENGRAILED2 and OTX2, their physiological functions have led to therapeutic strategies in animal models of human diseases, including Parkinson's disease, amyotrophic lateral sclerosis, amblyopia and anxiety-related disorders. In mesencephalic dopaminergic neurons which degenerate in Parkinson's disease, ENGRAILED1/2 have cell autonomous activities, but their transducing properties enables their use as therapeutic proteins. In contrast, in spinal alpha-motoneurons, which are lost in amyotrophic lateral sclerosis, ENGRAILED1 is supplied by V1 interneurons. Thus, its use as a therapeutic protein to protect alpha-motoneurons against degeneration mimics its normal non-cell autonomous neurotrophic activity. OTX2, synthesized and secreted by the choroid plexus, is transferred to parvalbumin interneurons and exerts regulatory functions controlling cerebral cortex plasticity. Understanding the latter OTX2 function has led to strategies for manipulating visual acuity and anxiety-like behavior in adult mice. In this review, we describe these cases and what is known about the involved molecular mechanisms. Because the transduction sequences are conserved in most of the few hundred homeoproteins, we argue how this family of molecules constitutes an important reservoir of physiological knowledge, with potential consequences in the search for new therapeutic strategies.}, } @article {pmid38549627, year = {2024}, author = {Turner, M and Belli, A and Castellani, RJ}, title = {Changes in Brain Structure and Function in a Multisport Cohort of Retired Female and Male Athletes, Many Years after Suffering a Concussion: Implications for Neuroplasticity and Neurodegenerative Disease Pathogenesis.}, journal = {Journal of Alzheimer's disease reports}, volume = {8}, number = {1}, pages = {501-516}, pmid = {38549627}, issn = {2542-4823}, support = {P30 AG072977/AG/NIA NIH HHS/United States ; }, abstract = {BACKGROUND: Cumulative effects of traumatic brain injury is of increasing concern, especially with respect to its role in the etiology and pathogenesis of neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis.

OBJECTIVE: Compare regional brain volume and connectivity between athletes with a history of concussion and controls.

METHODS: We evaluated whole-brain volumetric effects with Bayesian regression models and functional connectivity with network-based statistics, in 125 retired athletes (a mean of 11 reported concussions) and 36 matched controls.

RESULTS: Brain regions significantly lower in volume in the concussed group included the middle frontal gyrus, hippocampus, supramarginal gyrus, temporal pole, and inferior frontal gyrus. Conversely, brain regions significantly larger included the hippocampal and collateral sulcus, middle occipital gyrus, medial orbital gyrus, caudate nucleus, lateral orbital gyrus, and medial postcentral gyrus. Functional connectivity analyses revealed increased edge strength, most marked in motor domains. Numerous edges of this network strengthened in athletes were significantly weakened with concussion. Aligned to meta-analytic neuroimaging data, the observed changes suggest functional enhancement within the motor, sensory, coordination, balance, and visual processing domains in athletes, attenuated by concussive head injury with a negative impact on memory and language.

CONCLUSIONS: These findings suggest that engagement in sport may benefit the brain across numerous domains, but also highlights the potentially damaging effects of concussive head injury. Future studies with longitudinal cohorts including autopsy examination are needed to determine whether the latter reflects tissue loss from brain shearing, or the onset of a progressive Alzheimer's disease like proteinopathy.}, } @article {pmid38548902, year = {2024}, author = {Cicardi, ME and Kankate, V and Sriramoji, S and Krishnamurthy, K and Markandaiah, SS and Verdone, BM and Girdhar, A and Nelson, A and Rivas, LB and Boehringer, A and Haeusler, AR and Pasinelli, P and Guo, L and Trotti, D}, title = {The nuclear import receptor Kapβ2 modifies neurotoxicity mediated by poly(GR) in C9orf72-linked ALS/FTD.}, journal = {Communications biology}, volume = {7}, number = {1}, pages = {376}, pmid = {38548902}, issn = {2399-3642}, support = {RF1 NS114128/NS/NINDS NIH HHS/United States ; R21 NS090912/NS/NINDS NIH HHS/United States ; RF1 AG057882/AG/NIA NIH HHS/United States ; R01 NS109150/NS/NINDS NIH HHS/United States ; R35 GM138109/GM/NIGMS NIH HHS/United States ; }, mesh = {Humans ; *Frontotemporal Dementia/genetics ; *Amyotrophic Lateral Sclerosis/genetics/metabolism ; Active Transport, Cell Nucleus ; C9orf72 Protein/genetics ; DNA-Binding Proteins/genetics/metabolism ; Receptors, Cytoplasmic and Nuclear/metabolism ; }, abstract = {Expanded intronic G4C2 repeats in the C9ORF72 gene cause amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). These intronic repeats are translated through a non-AUG-dependent mechanism into five different dipeptide repeat proteins (DPRs), including poly-glycine-arginine (GR), which is aggregation-prone and neurotoxic. Here, we report that Kapβ2 and GR interact, co-aggregating, in cultured neurons in-vitro and CNS tissue in-vivo. Importantly, this interaction significantly decreased the risk of death of cultured GR-expressing neurons. Downregulation of Kapβ2 is detrimental to their survival, whereas increased Kapβ2 levels mitigated GR-mediated neurotoxicity. As expected, GR-expressing neurons displayed TDP-43 nuclear loss. Raising Kapβ2 levels did not restore TDP-43 into the nucleus, nor did alter the dynamic properties of GR aggregates. Overall, our findings support the design of therapeutic strategies aimed at up-regulating Kapβ2 expression levels as a potential new avenue for contrasting neurodegeneration in C9orf72-ALS/FTD.}, } @article {pmid38548323, year = {2024}, author = {Goldacre, R and Trubshaw, M and Morris, EJA and Talbot, K and Goldacre, MJ and Thompson, AG and Turner, MR}, title = {Venous thromboembolism risk in amyotrophic lateral sclerosis: a hospital record-linkage study.}, journal = {Journal of neurology, neurosurgery, and psychiatry}, volume = {95}, number = {10}, pages = {912-918}, pmid = {38548323}, issn = {1468-330X}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/epidemiology/complications ; *Venous Thromboembolism/epidemiology/prevention & control ; Male ; Female ; Aged ; Middle Aged ; Retrospective Studies ; Incidence ; England/epidemiology ; Risk Factors ; Adult ; Aged, 80 and over ; Medical Record Linkage ; Case-Control Studies ; Pulmonary Embolism/epidemiology ; }, abstract = {BACKGROUND: Venous thromboembolism (VTE) can occur in amyotrophic lateral sclerosis (ALS) and pulmonary embolism causes death in a minority of cases. The benefits of preventing VTE must be weighed against the risks. An accurate estimate of the incidence of VTE in ALS is crucial to assessing this balance.

METHODS: This retrospective record-linkage cohort study derived data from the Hospital Episode Statistics database, covering admissions to England's hospitals from 1 April 2003 to 31 December 2019 and included 21 163 patients with ALS and 17 425 337 controls. Follow-up began at index admission and ended at VTE admission, death or 2 years (whichever came sooner). Adjusted HRs (aHRs) for VTE were calculated, controlling for confounders.

RESULTS: The incidence of VTE in the ALS cohort was 18.8/1000 person-years. The relative risk of VTE in ALS was significantly greater than in controls (aHR 2.7, 95% CI 2.4 to 3.0). The relative risk of VTE in patients with ALS under 65 years was five times higher than controls (aHR 5.34, 95% CI 4.6 to 6.2), and higher than that of patients over 65 years compared with controls (aHR 1.86, 95% CI 1.62 to 2.12).

CONCLUSIONS: Patients with ALS are at a higher risk of developing VTE, but this is similar in magnitude to that reported in other chronic neurological conditions associated with immobility, such as multiple sclerosis, which do not routinely receive VTE prophylaxis. Those with ALS below the median age of symptom onset have a notably higher relative risk. A reappraisal of the case for routine antithrombotic therapy in those diagnosed with ALS now requires a randomised controlled trial.}, } @article {pmid38548305, year = {2024}, author = {Tilsley, P and Moutiez, A and Brodovitch, A and Mendili, MME and Testud, B and Zaaraoui, W and Verschueren, A and Attarian, S and Guye, M and Boucraut, J and Grapperon, AM and Stellmann, JP}, title = {Neurofilament Light Chain Levels Interact with Neurodegenerative Patterns and Motor Neuron Dysfunction in Amyotrophic Lateral Sclerosis.}, journal = {AJNR. American journal of neuroradiology}, volume = {45}, number = {4}, pages = {494-503}, pmid = {38548305}, issn = {1936-959X}, mesh = {Male ; Humans ; Middle Aged ; *Amyotrophic Lateral Sclerosis/diagnostic imaging ; Retrospective Studies ; Prospective Studies ; *Neurodegenerative Diseases ; Intermediate Filaments ; Motor Neurons/pathology ; Magnetic Resonance Imaging/methods ; Atrophy/pathology ; }, abstract = {BACKGROUND AND PURPOSE: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease involving rapid motor neuron degeneration leading to brain, primarily precentral, atrophy. Neurofilament light chains are a robust prognostic biomarker highly specific to ALS, yet associations between neurofilament light chains and MR imaging outcomes are not well-understood. We investigated the role of neurofilament light chains as mediators among neuroradiologic assessments, precentral neurodegeneration, and disability in ALS.

MATERIALS AND METHODS: We retrospectively analyzed a prospective cohort of 29 patients with ALS (mean age, 56 [SD, 12] years; 18 men) and 36 controls (mean age, 49 [SD, 11] years; 18 men). Patients underwent 3T (n = 19) or 7T (n = 10) MR imaging, serum (n = 23) and CSF (n = 15) neurofilament light chains, and clinical (n = 29) and electrophysiologic (n = 27) assessments. The control group had equivalent 3T (n = 25) or 7T (n = 11) MR imaging. Two trained neuroradiologists performed blinded qualitative assessments of MR imaging anomalies (n = 29 patients, n = 36 controls). Associations between precentral cortical thickness and neurofilament light chains and clinical and electrophysiologic data were analyzed.

RESULTS: We observed extensive cortical thinning in patients compared with controls. MR imaging analyses showed significant associations between precentral cortical thickness and bulbar or arm impairment following distributions corresponding to the motor homunculus. Finally, uncorrected results showed positive interactions among precentral cortical thickness, serum neurofilament light chains, and electrophysiologic outcomes. Qualitative MR imaging anomalies including global atrophy (P = .003) and FLAIR corticospinal tract hypersignal anomalies (P = .033), correlated positively with serum neurofilament light chains.

CONCLUSIONS: Serum neurofilament light chains may be an important mediator between clinical symptoms and neuronal loss according to cortical thickness. Furthermore, MR imaging anomalies might have underestimated prognostic value because they seem to indicate higher serum neurofilament light chain levels.}, } @article {pmid38548126, year = {2024}, author = {Krut', VG and Kalinichenko, AL and Maltsev, DI and Jappy, D and Shevchenko, EK and Podgorny, OV and Belousov, VV}, title = {Optogenetic and chemogenetic approaches for modeling neurological disorders in vivo.}, journal = {Progress in neurobiology}, volume = {235}, number = {}, pages = {102600}, doi = {10.1016/j.pneurobio.2024.102600}, pmid = {38548126}, issn = {1873-5118}, mesh = {Animals ; Humans ; Optogenetics/methods ; *Epilepsy ; Models, Animal ; *Parkinson Disease ; Neuropathology ; }, abstract = {Animal models of human neurological disorders provide valuable experimental tools which enable us to study various aspects of disorder pathogeneses, ranging from structural abnormalities and disrupted metabolism and signaling to motor and mental deficits, and allow us to test novel therapies in preclinical studies. To be valid, these animal models should recapitulate complex pathological features at the molecular, cellular, tissue, and behavioral levels as closely as possible to those observed in human subjects. Pathological states resembling known human neurological disorders can be induced in animal species by toxins, genetic factors, lesioning, or exposure to extreme conditions. In recent years, novel animal models recapitulating neuropathologies in humans have been introduced. These animal models are based on synthetic biology approaches: opto- and chemogenetics. In this paper, we review recent opto- and chemogenetics-based animal models of human neurological disorders. These models allow for the creation of pathological states by disrupting specific processes at the cellular level. The artificial pathological states mimic a range of human neurological disorders, such as aging-related dementia, Alzheimer's and Parkinson's diseases, amyotrophic lateral sclerosis, epilepsy, and ataxias. Opto- and chemogenetics provide new opportunities unavailable with other animal models of human neurological disorders. These techniques enable researchers to induce neuropathological states varying in severity and ranging from acute to chronic. We also discuss future directions for the development and application of synthetic biology approaches for modeling neurological disorders.}, } @article {pmid38544185, year = {2024}, author = {Albán-Escobar, M and Navarrete-Arroyo, P and De la Cruz-Guevara, DR and Tobar-Quevedo, J}, title = {Assistance Device Based on SSVEP-BCI Online to Control a 6-DOF Robotic Arm.}, journal = {Sensors (Basel, Switzerland)}, volume = {24}, number = {6}, pages = {}, pmid = {38544185}, issn = {1424-8220}, mesh = {Humans ; *Brain-Computer Interfaces ; *Robotic Surgical Procedures ; Electroencephalography/methods ; *Self-Help Devices ; Evoked Potentials, Visual ; Photic Stimulation ; }, abstract = {This paper explores the potential benefits of integrating a brain-computer interface (BCI) utilizing the visual-evoked potential paradigm (SSVEP) with a six-degrees-of-freedom (6-DOF) robotic arm to enhance rehabilitation tools. The SSVEP-BCI employs electroencephalography (EEG) as a method of measuring neural responses inside the occipital lobe in reaction to pre-established visual stimulus frequencies. The BCI offline and online studies yielded accuracy rates of 75% and 83%, respectively, indicating the efficacy of the system in accurately detecting and capturing user intent. The robotic arm achieves planar motion by utilizing a total of five control frequencies. The results of this experiment exhibited a high level of precision and consistency, as indicated by the recorded values of ±0.85 and ±1.49 cm for accuracy and repeatability, respectively. Moreover, during the performance tests conducted with the task of constructing a square within each plane, the system demonstrated accuracy of 79% and 83%. The use of SSVEP-BCI and a robotic arm together shows promise and sets a solid foundation for the development of assistive technologies that aim to improve the health of people with amyotrophic lateral sclerosis, spina bifida, and other related diseases.}, } @article {pmid38542501, year = {2024}, author = {Niu, Y and Pal, A and Szewczyk, B and Japtok, J and Naumann, M and Glaß, H and Hermann, A}, title = {Cell-Type-Dependent Recruitment Dynamics of FUS Protein at Laser-Induced DNA Damage Sites.}, journal = {International journal of molecular sciences}, volume = {25}, number = {6}, pages = {}, pmid = {38542501}, issn = {1422-0067}, support = {na//Nomis Foundation/ ; na//Hermann und Lilly Schilling-Stiftung/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism ; RNA-Binding Protein FUS/genetics/metabolism ; *Induced Pluripotent Stem Cells/metabolism ; DNA Damage ; Mutation ; }, abstract = {Increased signs of DNA damage have been associated to aging and neurodegenerative diseases. DNA damage repair mechanisms are tightly regulated and involve different pathways depending on cell types and proliferative vs. postmitotic states. Amongst them, fused in sarcoma (FUS) was reported to be involved in different pathways of single- and double-strand break repair, including an early recruitment to DNA damage. FUS is a ubiquitously expressed protein, but if mutated, leads to a more or less selective motor neurodegeneration, causing amyotrophic lateral sclerosis (ALS). Of note, ALS-causing mutation leads to impaired DNA damage repair. We thus asked whether FUS recruitment dynamics differ across different cell types putatively contributing to such cell-type-specific vulnerability. For this, we generated engineered human induced pluripotent stem cells carrying wild-type FUS-eGFP and analyzed different derivatives from these, combining a laser micro-irradiation technique and a workflow to analyze the real-time process of FUS at DNA damage sites. All cells showed FUS recruitment to DNA damage sites except for hiPSC, with only 70% of cells recruiting FUS. In-depth analysis of the kinetics of FUS recruitment at DNA damage sites revealed differences among cellular types in response to laser-irradiation-induced DNA damage. Our work suggests a cell-type-dependent recruitment behavior of FUS during the DNA damage response and repair procedure. The presented workflow might be a valuable tool for studying the proteins recruited at the DNA damage site in a real-time course.}, } @article {pmid38542497, year = {2024}, author = {Nemeth, C and Banik, NL and Haque, A}, title = {Disruption of Neuromuscular Junction Following Spinal Cord Injury and Motor Neuron Diseases.}, journal = {International journal of molecular sciences}, volume = {25}, number = {6}, pages = {}, pmid = {38542497}, issn = {1422-0067}, support = {R21 NS118393/NS/NINDS NIH HHS/United States ; I01 BX001262/BX/BLRD VA/United States ; 1R21NS118393-01/NH/NIH HHS/United States ; I01 BX004269/BX/BLRD VA/United States ; I01 BX006101/BX/BLRD VA/United States ; IK6 BX005964/BX/BLRD VA/United States ; }, mesh = {Humans ; Neuromuscular Junction/metabolism ; Motor Neurons/metabolism ; Muscle Fibers, Skeletal/metabolism ; Spinal Cord/metabolism ; *Amyotrophic Lateral Sclerosis/metabolism ; *Spinal Cord Injuries/metabolism ; }, abstract = {The neuromuscular junction (NMJ) is a crucial structure that connects the cholinergic motor neurons to the muscle fibers and allows for muscle contraction and movement. Despite the interruption of the supraspinal pathways that occurs in spinal cord injury (SCI), the NMJ, innervated by motor neurons below the injury site, has been found to remain intact. This highlights the importance of studying the NMJ in rodent models of various nervous system disorders, such as amyotrophic lateral sclerosis (ALS), Charcot-Marie-Tooth disease (CMT), spinal muscular atrophy (SMA), and spinal and bulbar muscular atrophy (SBMA). The NMJ is also involved in myasthenic disorders, such as myasthenia gravis (MG), and is vulnerable to neurotoxin damage. Thus, it is important to analyze the integrity of the NMJ in rodent models during the early stages of the disease, as this may allow for a better understanding of the condition and potential treatment options. The spinal cord also plays a crucial role in the functioning of the NMJ, as the junction relays information from the spinal cord to the muscle fibers, and the integrity of the NMJ could be disrupted by SCI. Therefore, it is vital to study SCI and muscle function when studying NMJ disorders. This review discusses the formation and function of the NMJ after SCI and potential interventions that may reverse or improve NMJ dysfunction, such as exercise, nutrition, and trophic factors.}, } @article {pmid38542306, year = {2024}, author = {Marshall Moscon, SL and Connor, JR}, title = {HFE Mutations in Neurodegenerative Disease as a Model of Hormesis.}, journal = {International journal of molecular sciences}, volume = {25}, number = {6}, pages = {}, pmid = {38542306}, issn = {1422-0067}, mesh = {Mice ; Animals ; *Neurodegenerative Diseases/genetics ; Hemochromatosis Protein/genetics ; Histocompatibility Antigens Class I/genetics ; Hormesis ; Mutation ; Iron/metabolism ; }, abstract = {Common variants in the iron regulatory protein HFE contribute to systematically increased iron levels, yet the effects in the brain are not fully characterized. It is commonly believed that iron dysregulation is a key contributor to neurodegenerative disease due to iron's ability to catalyze reactive oxygen species production. However, whether HFE variants exacerbate or protect against neurodegeneration has been heavily debated. Some claim that mutated HFE exacerbates oxidative stress and neuroinflammation, thus predisposing carriers to neurodegeneration-linked pathologies. However, H63D HFE has also been shown to slow the progression of multiple neurodegenerative diseases and to protect against environmental toxins that cause neurodegeneration. These conflicting results showcase the need to further understand the contribution of HFE variants to neurodegenerative disease heterogeneity. Data from mouse models consistently demonstrate robust neuroprotection against toxins known to increase the risk of neurodegenerative disease. This may represent an adaptive, or hormetic, response to increased iron, which leaves cells better protected against future stressors. This review describes the current research regarding the contribution of HFE variants to neurodegenerative disease prognosis in the context of a hormetic model. To our knowledge, this is the first time that a hormetic model for neurodegenerative disease has been presented.}, } @article {pmid38542223, year = {2024}, author = {Salvatori, I and Nesci, V and Spalloni, A and Marabitti, V and Muzzi, M and Zenuni, H and Scaricamazza, S and Rosina, M and Fenili, G and Goglia, M and Boffa, L and Massa, R and Moreno, S and Mercuri, NB and Nazio, F and Longone, P and Ferri, A and Valle, C}, title = {Trimetazidine Improves Mitochondrial Dysfunction in SOD1[G93A] Cellular Models of Amyotrophic Lateral Sclerosis through Autophagy Activation.}, journal = {International journal of molecular sciences}, volume = {25}, number = {6}, pages = {}, pmid = {38542223}, issn = {1422-0067}, support = {CNR IFT DBA.AD005.225 -NUTRAGE- FOE2021//National Research Council/ ; RF-2019-12369105//Ministero della Salute/ ; HyperALS//Fondazione Italiana di Ricerca per la Sclerosi Laterale Amiotrofica/ ; 'Unraveling the protective effects of NOS1AP in the rescue of TDP-43 loss of function pathological mechanisms//Fondazione Italiana di Ricerca per la Sclerosi Laterale Amiotrofica/ ; Ref. 27019//Italian Association for Cancer Research/ ; Prot. GeCoWEB n. A0375-2020- 36668//Regione Lazio/ ; The Grant of Excellence Departments 2023-2027//Ministero dell'Università e Ricerca Italy/ ; }, mesh = {Mice ; Animals ; Humans ; *Amyotrophic Lateral Sclerosis/metabolism ; Superoxide Dismutase-1/metabolism ; *Trimetazidine/pharmacology/therapeutic use ; Mice, Transgenic ; Leukocytes, Mononuclear/metabolism ; Superoxide Dismutase/metabolism ; Autophagy ; *Mitochondrial Diseases ; Disease Models, Animal ; }, abstract = {Amyotrophic Lateral Sclerosis (ALS) is considered the prototype of motor neuron disease, characterized by motor neuron loss and muscle waste. A well-established pathogenic hallmark of ALS is mitochondrial failure, leading to bioenergetic deficits. So far, pharmacological interventions for the disease have proven ineffective. Trimetazidine (TMZ) is described as a metabolic modulator acting on different cellular pathways. Its efficacy in enhancing muscular and cardiovascular performance has been widely described, although its molecular target remains elusive. We addressed the molecular mechanisms underlying TMZ action on neuronal experimental paradigms. To this aim, we treated murine SOD1[G93A]-model-derived primary cultures of cortical and spinal enriched motor neurons, as well as a murine motor-neuron-like cell line overexpressing SOD1[G93A], with TMZ. We first characterized the bioenergetic profile of the cell cultures, demonstrating significant mitochondrial dysfunction that is reversed by acute TMZ treatments. We then investigated the effect of TMZ in promoting autophagy processes and its impact on mitochondrial morphology. Finally, we demonstrated the effectiveness of TMZ in terms of the mitochondrial functionality of ALS-rpatient-derived peripheral blood mononuclear cells (PBMCs). In summary, our results emphasize the concept that targeting mitochondrial dysfunction may represent an effective therapeutic strategy for ALS. The findings demonstrate that TMZ enhances mitochondrial performance in motor neuron cells by activating autophagy processes, particularly mitophagy. Although further investigations are needed to elucidate the precise molecular pathways involved, these results hold critical implications for the development of more effective and specific derivatives of TMZ for ALS treatment.}, } @article {pmid38540795, year = {2024}, author = {Gascón, E and Zaragoza, P and Calvo, AC and Osta, R}, title = {Sporadic Amyotrophic Lateral Sclerosis Skeletal Muscle Transcriptome Analysis: A Comprehensive Examination of Differentially Expressed Genes.}, journal = {Biomolecules}, volume = {14}, number = {3}, pages = {}, pmid = {38540795}, issn = {2218-273X}, support = {PI17/00949//Instituto de Salud Carlos III/ ; A19_23R//"LAGENBIO GRUPO INVESTIGACION"/ ; CIBER-358 NED-612-CB18/05/00037//Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas/ ; }, mesh = {Humans ; Transcriptome/genetics ; *Amyotrophic Lateral Sclerosis/genetics/metabolism ; *MicroRNAs/genetics/metabolism ; Muscle, Skeletal/metabolism ; Biomarkers ; }, abstract = {Amyotrophic lateral sclerosis (ALS) that comprises sporadic (sALS) and familial (fALS) cases, is a devastating neurodegenerative disorder characterized by progressive degeneration of motor neurons, leading to muscle atrophy and various clinical manifestations. However, the complex underlying mechanisms affecting this disease are not yet known. On the other hand, there is also no good prognosis of the disease due to the lack of biomarkers and therapeutic targets. Therefore, in this study, by means of bioinformatics analysis, sALS-affected muscle tissue was analyzed using the GEO GSE41414 dataset, identifying 397 differentially expressed genes (DEGs). Functional analysis revealed 320 up-regulated DEGs associated with muscle development and 77 down-regulated DEGs linked to energy metabolism. Protein-protein interaction network analysis identified 20 hub genes, including EIF4A1, HNRNPR and NDUFA4. Furthermore, miRNA target gene networks revealed 17 miRNAs linked to hub genes, with hsa-mir-206, hsa-mir-133b and hsa-mir-100-5p having been previously implicated in ALS. This study presents new potential biomarkers and therapeutic targets for ALS by correlating the information obtained with a comprehensive literature review, providing new potential targets to study their role in ALS.}, } @article {pmid38540776, year = {2024}, author = {Hughes, LS and Fröhlich, A and Pfaff, AL and Bubb, VJ and Quinn, JP and Kõks, S}, title = {Exploring SVA Insertion Polymorphisms in Shaping Differential Gene Expressions in the Central Nervous System.}, journal = {Biomolecules}, volume = {14}, number = {3}, pages = {}, pmid = {38540776}, issn = {2218-273X}, support = {1234//Andrzej Wlodarski Memorial Research Fund/ ; 1234//Multiple Sclerosis Western Australia/ ; }, mesh = {Humans ; *Retroelements ; *Amyotrophic Lateral Sclerosis/genetics ; Minisatellite Repeats ; DNA Transposable Elements ; Central Nervous System ; Gene Expression ; }, abstract = {Transposable elements (TEs) are repetitive elements which make up around 45% of the human genome. A class of TEs, known as SINE-VNTR-Alu (SVA), demonstrate the capacity to mobilise throughout the genome, resulting in SVA polymorphisms for their presence or absence within the population. Although studies have previously highlighted the involvement of TEs within neurodegenerative diseases, such as Parkinson's disease and amyotrophic lateral sclerosis (ALS), the exact mechanism has yet to be identified. In this study, we used whole-genome sequencing and RNA sequencing data of ALS patients and healthy controls from the New York Genome Centre ALS Consortium to elucidate the influence of reference SVA elements on gene expressions genome-wide within central nervous system (CNS) tissues. To investigate this, we applied a matrix expression quantitative trait loci analysis and demonstrate that reference SVA insertion polymorphisms can significantly modulate the expression of numerous genes, preferentially in the trans position and in a tissue-specific manner. We also highlight that SVAs significantly regulate mitochondrial genes as well as genes within the HLA and MAPT loci, previously associated within neurodegenerative diseases. In conclusion, this study continues to bring to light the effects of polymorphic SVAs on gene regulation and further highlights the importance of TEs within disease pathology.}, } @article {pmid38540709, year = {2024}, author = {Stoklund Dittlau, K and Freude, K}, title = {Astrocytes: The Stars in Neurodegeneration?.}, journal = {Biomolecules}, volume = {14}, number = {3}, pages = {}, pmid = {38540709}, issn = {2218-273X}, support = {R434-2023-242//Lundbeck Foundation/ ; 2078-00002B//Innovation Fund Denmark/ ; NNF21OC0071571//Novo Nordisk Foundation/ ; N/A//Alzheimer Foundation Denmark/ ; }, mesh = {Humans ; Astrocytes/physiology ; *Neurodegenerative Diseases ; *Alzheimer Disease ; *Parkinson Disease ; *Amyotrophic Lateral Sclerosis/therapy ; }, abstract = {Today, neurodegenerative disorders like Alzheimer's disease (AD), Parkinson's disease (PD), frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) affect millions of people worldwide, and as the average human lifespan increases, similarly grows the number of patients. For many decades, cognitive and motoric decline has been explained by the very apparent deterioration of neurons in various regions of the brain and spinal cord. However, more recent studies show that disease progression is greatly influenced by the vast population of glial cells. Astrocytes are traditionally considered star-shaped cells on which neurons rely heavily for their optimal homeostasis and survival. Increasing amounts of evidence depict how astrocytes lose their supportive functions while simultaneously gaining toxic properties during neurodegeneration. Many of these changes are similar across various neurodegenerative diseases, and in this review, we highlight these commonalities. We discuss how astrocyte dysfunction drives neuronal demise across a wide range of neurodegenerative diseases, but rather than categorizing based on disease, we aim to provide an overview based on currently known mechanisms. As such, this review delivers a different perspective on the disease causes of neurodegeneration in the hope to encourage further cross-disease studies into shared disease mechanisms, which might ultimately disclose potentially common therapeutic entry points across a wide panel of neurodegenerative diseases.}, } @article {pmid38540591, year = {2024}, author = {Brito, O and Fregonezi, G and Pondofe, K and Vieira, RGDS and Ribeiro, T and Dourado Júnior, ME and Fidelix, EC and Nagem, D and Valentim, R and Sarmento, A and Resqueti, V}, title = {Assessment of the Clinical and Functional Health Status of Patients with Amyotrophic Lateral Sclerosis during the COVID-19 Pandemic in Brazil Using Telemedicine.}, journal = {Healthcare (Basel, Switzerland)}, volume = {12}, number = {6}, pages = {}, pmid = {38540591}, issn = {2227-9032}, support = {2021OB805920//Coordenação de Aperfeicoamento de Pessoal de Nível Superior/ ; 305960/2021-0//National Council for Scientific and Technological Development/ ; 316937/2021-5//National Council for Scientific and Technological Development/ ; }, abstract = {This study aimed to monitor the clinical and functional progression of patients with amyotrophic lateral sclerosis (ALS) and adjust ventilatory support during the COVID-19 pandemic in Brazil using telemedicine. This longitudinal case series included five evaluations from January 2019 to June 2021. The first and second assessments were performed in person and consisted of pulmonary function, respiratory muscle strength, functionality (ALS Functional Rating Scale-Revised [ALSFRS-R]) and disease staging (King's College criteria). The use of non-invasive ventilation (NIV), ALSFRS-R, and disease staging were assessed in the third, fourth, and fifth assessments during the COVID-19 pandemic, using telemedicine. The rate of functional decline was calculated by the difference in the total score of ALSFRS-R between evaluations. A cutoff of 0.77 in the ALSFRS-R was used to characterize the speed of functional decline. Eleven patients (mean age of 51 years, eight males) were assessed. The total score of the ALSFRS-R (p < 0.01) and its motor domain (p < 0.01) reduced significantly during the pandemic. NIV prescription increased from 54.4% to 83.3%. Telemedicine helped with the clinical and functional follow-up of patients with ALS.}, } @article {pmid38540370, year = {2024}, author = {Ivantsik, O and John, A and Kydonopoulou, K and Mitropoulos, K and Gerou, S and Ali, BR and Patrinos, GP}, title = {Novel Pathogenic Variants Leading to Sporadic Amyotrophic Lateral Sclerosis in Greek Patients.}, journal = {Genes}, volume = {15}, number = {3}, pages = {}, pmid = {38540370}, issn = {2073-4425}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/pathology ; Mutation ; Superoxide Dismutase-1/genetics ; Greece ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a rapidly progressive disease that affects motor neurons, leading to paralysis and death usually 3-5 years after the onset of symptoms. The investigation of both sporadic and familial ALS highlighted four main genes that contribute to the pathogenesis of the disease: SOD1, FUS, TARDBP and C9orf72. This study aims to provide a comprehensive investigation of genetic variants found in SOD1, FUS and TARDBP genes in Greek sporadic ALS (sALS) cases. Our sequencing analysis of the coding regions of the abovementioned genes that include the majority of the variants that lead to ALS in 32 sALS patients and 3 healthy relatives revealed 6 variants in SOD1, 19 variants in FUS and 37 variants in TARDBP, of which the SOD1 p.D90A and the FUS c.*356G>A (rs886051940) variants have been previously associated with ALS, while two novel nonsense pathogenic variants were also identified, namely FUS p.R241* and TDP-43 p.Y214*. Our study contributes to the worldwide effort toward clarifying the genetic basis of sALS to better understand the disease's molecular pathology.}, } @article {pmid38540369, year = {2024}, author = {Souza, PVS and Serrano, PL and Farias, IB and Machado, RIL and Badia, BML and Oliveira, HB and Barbosa, AS and Pereira, CA and Moreira, VF and Chieia, MAT and Barbosa, AR and Braga, VL and Pinto, WBVR and Oliveira, ASB}, title = {Clinical and Genetic Aspects of Juvenile Amyotrophic Lateral Sclerosis: A Promising Era Emerges.}, journal = {Genes}, volume = {15}, number = {3}, pages = {}, pmid = {38540369}, issn = {2073-4425}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/genetics ; Motor Neurons ; Neuroimaging ; }, abstract = {Juvenile Amyotrophic Lateral Sclerosis is a genetically heterogeneous neurodegenerative disorder, which is frequently misdiagnosed due to low clinical suspicion and little knowledge about disease characteristics. More than 20 different genetic loci have been associated with both sporadic and familial juvenile Amyotrophic Lateral Sclerosis. Currently, almost 40% of cases have an identifiable monogenic basis; type 6, associated with FUS gene variants, is the most prevalent globally. Despite several upper motor neuron-dominant forms being generally associated with long-standing motor symptoms and slowly progressive course, certain subtypes with lower motor neuron-dominant features and early bulbar compromise lead to rapidly progressive motor handicap. For some monogenic forms, there is a well-established genotypic-phenotypic correlation. There are no specific biochemical and neuroimaging biomarkers for the diagnosis of juvenile Amyotrophic Lateral Sclerosis. There are several inherited neurodegenerative and neurometabolic disorders which can lead to the signs of motor neuron impairment. This review emphasizes the importance of high clinical suspicion, assessment, and proper diagnostic work-up for juvenile Amyotrophic Lateral Sclerosis.}, } @article {pmid38538647, year = {2024}, author = {Wang, X and Chen, H and Chang, Z and Zhang, J and Xie, D}, title = {Genetic causal role of body mass index in multiple neurological diseases.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {7256}, pmid = {38538647}, issn = {2045-2322}, support = {82274493//National Natural Science Foundation of China/ ; 81874389//National Natural Science Foundation of China/ ; }, mesh = {Humans ; Body Mass Index ; *Amyotrophic Lateral Sclerosis/genetics ; Genome-Wide Association Study ; *Nervous System Diseases/genetics ; *Parkinson Disease/genetics ; *Multiple Sclerosis/genetics ; *Alzheimer Disease/genetics ; *Ischemic Stroke ; Mendelian Randomization Analysis ; Obesity/genetics ; }, abstract = {Body mass index (BMI) is a crucial health indicator for obesity. With the progression of socio-economic status and alterations in lifestyle, an increasing number of global populations are at risk of obesity. Given the complexity and severity of neurological diseases, early identification of risk factors is vital for the diagnosis and prognosis of such diseases. In this study, we employed Mendelian randomization (MR) analysis utilizing the most comprehensive genome-wide association study (GWAS) data to date. We selected single nucleotide polymorphisms (SNPs) that are unaffected by confounding factors and reverse causality as instrumental variables. These variables were used to evaluate the genetic and causal relationships between Body Mass Index (BMI) and various neurological diseases, including Parkinson's Disease (PD), Alzheimer's Disease (AD), Amyotrophic Lateral Sclerosis (ALS), Multiple Sclerosis (MS), Ischemic Stroke (IS), and Epilepsy (EP). The Inverse Variance Weighted (IVW) analysis indicated that there was no significant causal relationship between Body Mass Index (BMI) indicators and PD (P-value = 0.511), AD (P-value = 0.076), ALS (P-value = 0.641), EP (P-value = 0.380). However, a causal relationship was found between BMI indicators and MS (P-value = 0.035), and IS (P-value = 0.000), with the BMI index positively correlated with the risk of both diseases. The Cochran's Q test for MR-IVW showed no heterogeneity in the MR analysis results between the BMI index and the neurological diseases (P > 0.05). The Egger intercept test for pleiotropy revealed no horizontal pleiotropy detected in any of the neurological diseases studied (P > 0.05). It was found that there was no causal relationship between BMI and PD, AD, ALS, EP, and a genetic causal association with MS, and IS. Meanwhile, the increase in BMI can lead to a higher risk of MS and IS, which reveals the critical role of obesity as a risk factor for specific neurological diseases in the pathogenesis of the diseases.}, } @article {pmid38538275, year = {2024}, author = {Ceccarelli, L and Verriello, L and Pauletto, G and Valente, M and Spadea, L and Salati, C and Zeppieri, M and Ius, T}, title = {The Role of Human Pluripotent Stem Cells in Amyotrophic Lateral Sclerosis: From Biological Mechanism to Practical Implications.}, journal = {Frontiers in bioscience (Landmark edition)}, volume = {29}, number = {3}, pages = {114}, doi = {10.31083/j.fbl2903114}, pmid = {38538275}, issn = {2768-6698}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/therapy/metabolism ; Motor Neurons/metabolism ; *Pluripotent Stem Cells/metabolism/pathology ; *Induced Pluripotent Stem Cells/metabolism/pathology ; }, abstract = {Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disorder, characterized by progressive loss of both upper and lower motor neurons, resulting in clinical features such as muscle weakness, paralysis, and ultimately, respiratory failure. Nowadays, there is not effective treatment to reverse the progression of the disease, that leads to death within 3-5 years after the onset. Nevertheless, the induced pluripotent stem cells (iPS) technology could be the answer, providing disease modelling, drug testing, and cell-based therapies for this pathology. The aim of this work was to conduct a literature review of the past 5 years about the role of iPS in ALS, to better define the neurobiological mechanisms involved in the pathogenesis and the potential future therapies. The review also deals with advanced and currently available technologies used to reprogram cell lines and generate human motor neurons in vitro, which represent the source to study the pathological processes, the relationship between phenotype and genotype, the disease progression and the potential therapeutic targets of these group of disorders. Specific treatment options with stem cells involve Advance Gene Editing Technology, neuroprotective agents, and cells or exosomes transplantation, aimed to replace dead or damaged nerve cells. In summary, this review comprehensively addresses the role of human pluripotent stem cells (hPSCs) in motor neuron diseases (MND), with a focus on physiopathology, diagnostic and prognostic implications, specific and potential future treatment options. Understanding the biological mechanisms and practical implications of hPSCs in MND is crucial for advancing therapeutic strategies and improving outcomes for patients affected by these devastating diseases.}, } @article {pmid38538227, year = {2024}, author = {Tan, EL and Lope, J and Bede, P}, title = {Harnessing Big Data in Amyotrophic Lateral Sclerosis: Machine Learning Applications for Clinical Practice and Pharmaceutical Trials.}, journal = {Journal of integrative neuroscience}, volume = {23}, number = {3}, pages = {58}, doi = {10.31083/j.jin2303058}, pmid = {38538227}, issn = {0219-6352}, support = {HRB EIA-2017-019/HRBI_/Health Research Board/Ireland ; JPND-Cofund-2-2019-/HRBI_/Health Research Board/Ireland ; SFI SP20/SP/8953/SFI_/Science Foundation Ireland/Ireland ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/drug therapy ; Big Data ; Biomarkers ; Machine Learning ; }, abstract = {The arrival of genotype-specific therapies in amyotrophic lateral sclerosis (ALS) signals the dawn of precision medicine in motor neuron diseases (MNDs). After decades of academic studies in ALS, we are now witnessing tangible clinical advances. An ever increasing number of well-designed descriptive studies have been published in recent years, characterizing typical disease-burden patterns in vivo and post mortem. Phenotype- and genotype-associated traits and "typical" propagation patterns have been described based on longitudinal clinical and biomarker data. The practical caveat of these studies is that they report "group-level", stereotyped trajectories representative of ALS as a whole. In the clinical setting, however, "group-level" biomarker signatures have limited practical relevance and what matters is the meaningful interpretation of data from a single individual. The increasing availability of large normative data sets, national registries, extant academic data, consortium repositories, and emerging data platforms now permit the meaningful interpretation of individual biomarker profiles and allow the categorization of single patients into relevant diagnostic, phenotypic, and prognostic categories. A variety of machine learning (ML) strategies have been recently explored in MND to demonstrate the feasibility of interpreting data from a single patient. Despite the considerable clinical prospects of classification models, a number of pragmatic challenges need to be overcome to unleash the full potential of ML in ALS. Cohort size limitations, administrative hurdles, data harmonization challenges, regulatory differences, methodological obstacles, and financial implications and are just some of the barriers to readily implement ML in routine clinical practice. Despite these challenges, machine-learning strategies are likely to be firmly integrated in clinical decision-making and pharmacological trials in the near future.}, } @article {pmid38536565, year = {2024}, author = {Vernikouskaya, I and Müller, HP and Ludolph, AC and Kassubek, J and Rasche, V}, title = {AI-assisted automatic MRI-based tongue volume evaluation in motor neuron disease (MND).}, journal = {International journal of computer assisted radiology and surgery}, volume = {19}, number = {8}, pages = {1579-1587}, pmid = {38536565}, issn = {1861-6429}, mesh = {Humans ; *Tongue/diagnostic imaging ; *Magnetic Resonance Imaging/methods ; *Motor Neuron Disease/diagnostic imaging/diagnosis ; Male ; Female ; Middle Aged ; Aged ; *Neural Networks, Computer ; Pilot Projects ; Imaging, Three-Dimensional/methods ; Amyotrophic Lateral Sclerosis/diagnostic imaging/diagnosis ; Adult ; }, abstract = {PURPOSE: Motor neuron disease (MND) causes damage to the upper and lower motor neurons including the motor cranial nerves, the latter resulting in bulbar involvement with atrophy of the tongue muscle. To measure tongue atrophy, an operator independent automatic segmentation of the tongue is crucial. The aim of this study was to apply convolutional neural network (CNN) to MRI data in order to determine the volume of the tongue.

METHODS: A single triplanar CNN of U-Net architecture trained on axial, coronal, and sagittal planes was used for the segmentation of the tongue in MRI scans of the head. The 3D volumes were processed slice-wise across the three orientations and the predictions were merged using different voting strategies. This approach was developed using MRI datasets from 20 patients with 'classical' spinal amyotrophic lateral sclerosis (ALS) and 20 healthy controls and, in a pilot study, applied to the tongue volume quantification to 19 controls and 19 ALS patients with the variant progressive bulbar palsy (PBP).

RESULTS: Consensus models with softmax averaging and majority voting achieved highest segmentation accuracy and outperformed predictions on single orientations and consensus models with union and unanimous voting. At the group level, reduction in tongue volume was not observed in classical spinal ALS, but was significant in the PBP group, as compared to controls.

CONCLUSION: Utilizing single U-Net trained on three orthogonal orientations with consequent merging of respective orientations in an optimized consensus model reduces the number of erroneous detections and improves the segmentation of the tongue. The CNN-based automatic segmentation allows for accurate quantification of the tongue volumes in all subjects. The application to the ALS variant PBP showed significant reduction of the tongue volume in these patients and opens the way for unbiased future longitudinal studies in diseases affecting tongue volume.}, } @article {pmid38535081, year = {2024}, author = {Liampas, I and Danga, F and Kyriakoulopoulou, P and Siokas, V and Stamati, P and Messinis, L and Dardiotis, E and Nasios, G}, title = {The Contribution of Functional Near-Infrared Spectroscopy (fNIRS) to the Study of Neurodegenerative Disorders: A Narrative Review.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {14}, number = {6}, pages = {}, pmid = {38535081}, issn = {2075-4418}, abstract = {Functional near-infrared spectroscopy (fNIRS) is an innovative neuroimaging method that offers several advantages over other commonly used modalities. This narrative review investigated the potential contribution of this method to the study of neurodegenerative disorders. Thirty-four studies involving patients with Alzheimer's disease (AD), mild cognitive impairment (MCI), frontotemporal dementia (FTD), Parkinson's disease (PD), or amyotrophic lateral sclerosis (ALS) and healthy controls were reviewed. Overall, it was revealed that the prefrontal cortex of individuals with MCI may engage compensatory mechanisms to support declining brain functions. A rightward shift was suggested to compensate for the loss of the left prefrontal capacity in the course of cognitive decline. In parallel, some studies reported the failure of compensatory mechanisms in MCI and early AD; this lack of appropriate hemodynamic responses may serve as an early biomarker of neurodegeneration. One article assessing FTD demonstrated a heterogeneous cortical activation pattern compared to AD, indicating that fNIRS may contribute to the challenging distinction of these conditions. Regarding PD, there was evidence that cognitive resources (especially executive function) were recruited to compensate for locomotor impairments. As for ALS, fNIRS data support the involvement of extra-motor networks in ALS, even in the absence of measurable cognitive impairment.}, } @article {pmid38535014, year = {2024}, author = {Goudie, A and Blaivas, M and Horn, R and Lien, WC and Michels, G and Wastl, D and Dietrich, CF}, title = {Ultrasound during Advanced Life Support-Help or Harm?.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {14}, number = {6}, pages = {}, pmid = {38535014}, issn = {2075-4418}, abstract = {Ultrasound is used in cardiopulmonary resuscitation (CPR) and advanced life support (ALS). However, there is divergence between the recommendations of many emergency and critical care societies who support its use and the recommendations of many international resuscitation organizations who either recommend against its use or recommend it only in limited circumstances. Ultrasound offers potential benefits of detecting reversable causes of cardiac arrest, allowing specific interventions. However, it also risks interfering with ALS protocols and increasing unhelpful interventions. As with many interventions in ALS, the evidence base for ultrasound use is weak, and well-designed randomized trials are needed. This paper reviews the current theory and evidence for harms and benefits.}, } @article {pmid38534355, year = {2024}, author = {Cohen, J and Mathew, A and Dourvetakis, KD and Sanchez-Guerrero, E and Pangeni, RP and Gurusamy, N and Aenlle, KK and Ravindran, G and Twahir, A and Isler, D and Sosa-Garcia, SR and Llizo, A and Bested, AC and Theoharides, TC and Klimas, NG and Kempuraj, D}, title = {Recent Research Trends in Neuroinflammatory and Neurodegenerative Disorders.}, journal = {Cells}, volume = {13}, number = {6}, pages = {}, pmid = {38534355}, issn = {2073-4409}, mesh = {Humans ; Neuroinflammatory Diseases ; Endothelial Cells ; *Induced Pluripotent Stem Cells ; *Neurodegenerative Diseases ; Inflammation ; }, abstract = {Neuroinflammatory and neurodegenerative disorders including Alzheimer's disease (AD), Parkinson's disease (PD), traumatic brain injury (TBI) and Amyotrophic lateral sclerosis (ALS) are chronic major health disorders. The exact mechanism of the neuroimmune dysfunctions of these disease pathogeneses is currently not clearly understood. These disorders show dysregulated neuroimmune and inflammatory responses, including activation of neurons, glial cells, and neurovascular unit damage associated with excessive release of proinflammatory cytokines, chemokines, neurotoxic mediators, and infiltration of peripheral immune cells into the brain, as well as entry of inflammatory mediators through damaged neurovascular endothelial cells, blood-brain barrier and tight junction proteins. Activation of glial cells and immune cells leads to the release of many inflammatory and neurotoxic molecules that cause neuroinflammation and neurodegeneration. Gulf War Illness (GWI) and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) are chronic disorders that are also associated with neuroimmune dysfunctions. Currently, there are no effective disease-modifying therapeutic options available for these diseases. Human induced pluripotent stem cell (iPSC)-derived neurons, astrocytes, microglia, endothelial cells and pericytes are currently used for many disease models for drug discovery. This review highlights certain recent trends in neuroinflammatory responses and iPSC-derived brain cell applications in neuroinflammatory disorders.}, } @article {pmid38534336, year = {2024}, author = {Sonkodi, B}, title = {Progressive Irreversible Proprioceptive Piezo2 Channelopathy-Induced Lost Forced Peripheral Oscillatory Synchronization to the Hippocampal Oscillator May Explain the Onset of Amyotrophic Lateral Sclerosis Pathomechanism.}, journal = {Cells}, volume = {13}, number = {6}, pages = {}, pmid = {38534336}, issn = {2073-4409}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism ; Syndecan-3 ; Mechanotransduction, Cellular ; *Channelopathies ; *Neurodegenerative Diseases ; Protons ; Proprioception/physiology ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a mysterious lethal multisystem neurodegenerative disease that gradually leads to the progressive loss of motor neurons. A recent non-contact dying-back injury mechanism theory for ALS proposed that the primary damage is an acquired irreversible intrafusal proprioceptive terminal Piezo2 channelopathy with underlying genetic and environmental risk factors. Underpinning this is the theory that excessively prolonged proprioceptive mechanotransduction under allostasis may induce dysfunctionality in mitochondria, leading to Piezo2 channelopathy. This microinjury is suggested to provide one gateway from physiology to pathophysiology. The chronic, but not irreversible, form of this Piezo2 channelopathy is implicated in many diseases with unknown etiology. Dry eye disease is one of them where replenishing synthetic proteoglycans promote nerve regeneration. Syndecans, especially syndecan-3, are proposed as the first critical link in this hierarchical ordered depletory pathomechanism as proton-collecting/distributing antennas; hence, they may play a role in ALS pathomechanism onset. Even more importantly, the shedding or charge-altering variants of Syndecan-3 may contribute to the Piezo2 channelopathy-induced disruption of the Piezo2-initiated proton-based ultrafast long-range signaling through VGLUT1 and VGLUT2. Thus, these alterations may not only cause disruption to ultrafast signaling to the hippocampus in conscious proprioception, but could disrupt the ultrafast proprioceptive signaling feedback to the motoneurons. Correspondingly, an inert Piezo2-initiated proton-based ultrafast signaled proprioceptive skeletal system is coming to light that is suggested to be progressively lost in ALS. In addition, the lost functional link of the MyoD family of inhibitor proteins, as auxiliary subunits of Piezo2, may not only contribute to the theorized acquired Piezo2 channelopathy, but may explain how these microinjured ion channels evolve to be principal transcription activators.}, } @article {pmid38533934, year = {2024}, author = {Deutsch, AJ}, title = {PICking out progressive PIC alterations in amyotrophic lateral sclerosis.}, journal = {Journal of neurophysiology}, volume = {131}, number = {5}, pages = {822-824}, pmid = {38533934}, issn = {1522-1598}, support = {NS091836//HHS | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; R01 NS131816/NS/NINDS NIH HHS/United States ; R01 AG067758/AG/NIA NIH HHS/United States ; AG067758//HHS | NIH | National Institute on Aging (NIA)/ ; R01 NS091836/NS/NINDS NIH HHS/United States ; NS131816//HHS | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/physiopathology/pathology ; Humans ; *Motor Neurons/physiology/pathology ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that causes motoneuron death. Alterations to motoneuron excitability in ALS are suspected to contribute to motoneuron degeneration. Therefore, mechanisms underlying changes in motoneuron excitability are being thoroughly investigated. A recent publication from Trajano et al. (Trajano GS, Orssatto LB, McCombe PA, Rivlin W, Tang L, Henderson RD. J Physiol 601: 4723-4735, 2023) examined temporal changes to persistent inward currents (PICs) in ALS patients. They show that delta frequency (ΔF, an estimate of PICs) has opposite temporal trends in stronger and weaker muscles of ALS patients. This study is very important to aid in the understanding of disease mechanisms. This Neuro Forum article explores some important considerations for interpreting the results of this study, including treatment effects, potential sex differences, and a lack of comparison to healthy individuals.}, } @article {pmid38533726, year = {2024}, author = {Alix, JJP and Plesia, M and Dudgeon, AP and Kendall, CA and Hewamadduma, C and Hadjivassiliou, M and Gorman, GS and Taylor, RW and McDermott, CJ and Shaw, PJ and Mead, RJ and Day, JC}, title = {Conformational fingerprinting with Raman spectroscopy reveals protein structure as a translational biomarker of muscle pathology.}, journal = {The Analyst}, volume = {149}, number = {9}, pages = {2738-2746}, pmid = {38533726}, issn = {1364-5528}, support = {/WT_/Wellcome Trust/United Kingdom ; }, mesh = {*Spectrum Analysis, Raman/methods ; Humans ; Animals ; *Biomarkers/analysis ; *Muscular Dystrophy, Duchenne/pathology/diagnosis ; Muscle, Skeletal/chemistry/pathology ; Mice ; Amyotrophic Lateral Sclerosis/diagnosis/pathology ; Male ; }, abstract = {Neuromuscular disorders are a group of conditions that can result in weakness of skeletal muscles. Examples include fatal diseases such as amyotrophic lateral sclerosis and conditions associated with high morbidity such as myopathies (muscle diseases). Many of these disorders are known to have abnormal protein folding and protein aggregates. Thus, easy to apply methods for the detection of such changes may prove useful diagnostic biomarkers. Raman spectroscopy has shown early promise in the detection of muscle pathology in neuromuscular disorders and is well suited to characterising the conformational profiles relating to protein secondary structure. In this work, we assess if Raman spectroscopy can detect differences in protein structure in muscle in the setting of neuromuscular disease. We utilise in vivo Raman spectroscopy measurements from preclinical models of amyotrophic lateral sclerosis and the myopathy Duchenne muscular dystrophy, together with ex vivo measurements of human muscle samples from individuals with and without myopathy. Using quantitative conformation profiling and matrix factorisation we demonstrate that quantitative 'conformational fingerprinting' can be used to identify changes in protein folding in muscle. Notably, myopathic conditions in both preclinical models and human samples manifested a significant reduction in α-helix structures, with concomitant increases in β-sheet and, to a lesser extent, nonregular configurations. Spectral patterns derived through non-negative matrix factorisation were able to identify myopathy with a high accuracy (79% in mouse, 78% in human tissue). This work demonstrates the potential of conformational fingerprinting as an interpretable biomarker for neuromuscular disorders.}, } @article {pmid38533300, year = {2024}, author = {Moskvin, SV}, title = {A brief literature review of low-level laser therapy for treating amyotrophic lateral sclerosis and confirmation of its effectiveness.}, journal = {BioMedicine}, volume = {14}, number = {1}, pages = {1-9}, pmid = {38533300}, issn = {2211-8020}, abstract = {INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with a steadily progressive course due to the death of central and peripheral motor neurons responsible for voluntary movements. Low-level laser therapy (LLLT) is a treatment method unique in its universality and efficacy, particularly for neurodegenerative diseases.

METHODS: In this review, we discuss the effect and application of LLLT in the treatment of ALS. A literature search for English and Russian publications for the keywords "Amyotrophic Lateral Sclerosis", "Low-Level Laser Therapy" was performed using PubMed, Scopus, Google Scholar, Web of Science and Russian Science Citation Index (RSCI) databases.

RESULTS: The article provided a brief literature review, substantiated the potential use of low-level laser therapy for ALS. The particular techniques of LLLT were developed.

CONCLUSION: Based on the results of several studies and many years of successful experience with low-level laser therapy in Russia we conclude that a LLLT technique, including intravenous laser blood illumination (ILBI), noninvasive laser blood illumination (NLBI), and local exposure, is a promising treatment method for ALS.}, } @article {pmid38532923, year = {2023}, author = {Howson, PJ}, title = {Foreign language acquisition of perceptually similar segments: evidence from Lower Sorbian.}, journal = {Open research Europe}, volume = {3}, number = {}, pages = {56}, pmid = {38532923}, issn = {2732-5121}, abstract = {Lower Sorbian is a moribund language spoken in Eastern Germany that features a three-way sibilant contrast, /s, ʂ, ɕ/. The vast majority of L1 speakers are above eighty years of age and virtually no young Sorbians learn Lower Sorbian as their first language. There are language revitalization programs in place, but this means that virtually all Lower Sorbian speakers are L2 learners whose first language is German. German, as opposed to Lower Sorbian, has a two-way sibilant contrast, /s, ʃ/. So, Lower Sorbian learners need to acquire a perceptually similar sibilant contrast, /ʂ, ɕ/, that commonly assimilates with a single L1 segment, /ʃ/. The two-to-one assimilation makes acquisition difficult. In this project, I examine the acquisition of the three-way sibilant contrast using ultrasound technology. The ultrasound data revealed that learners in the contemporary context do not produce a distinction between /ʂ, ɕ/ and only learners at an advanced level who had significant exposure to L1 speakers have acquired a three-way sibilant distinction. The findings are put into the context of models of L2 acquisition and generalized implications for foreign language acquisition are discussed.}, } @article {pmid38531942, year = {2024}, author = {Son, B and Lee, J and Ryu, S and Park, Y and Kim, SH}, title = {Timing and impact of percutaneous endoscopic gastrostomy insertion in patients with amyotrophic lateral sclerosis: a comprehensive analysis.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {7103}, pmid = {38531942}, issn = {2045-2322}, support = {BK21 FOUR//National Research Foundation of Korea/ ; RS-2023-00265515//National Research Foundation of Korea/ ; }, mesh = {Humans ; Gastrostomy/methods ; *Amyotrophic Lateral Sclerosis ; Retrospective Studies ; *Deglutition Disorders ; Weight Loss ; }, abstract = {Dysphagia is common in amyotrophic lateral sclerosis (ALS) patients, often requiring percutaneous endoscopic gastrostomy (PEG) for enteral nutrition. We retrospectively analyzed data from 188 Korean patients with ALS who underwent PEG tube insertion at five-time points: symptom onset (t1), diagnosis (t2), recommended time for gastrostomy (t3), PEG insertion (t4), and one-year post-insertion (t5). The recommended time point for gastrostomy (T-rec for gastrostomy) was defined as the earlier time point between a weight loss of more than 10% and advanced dysphagia indicated by the ALSFRS-R swallowing subscore of 2 or less. The T-rec for gastrostomy was reached at 22 months after symptom onset, followed by PEG insertion at 30 months, resulting in an 8-month delay. During the delay, the ALSFRS-R declined most rapidly at 1.7 points/month, compared to 0.8 points/month from symptom onset to diagnosis, 0.7 points/month from diagnosis to T-rec for gastrostomy, and 0.6 points/month after the PEG insertion. It is crucial to discuss PEG insertion before significant weight loss or severe dysphagia occurs and minimize the delay between the recommended time for gastrostomy and the actual PEG insertion. A stratified and individualized multidisciplinary team approach with careful symptom monitoring and proactive management plans, including early PEG insertion, should be prioritized to improve patient outcomes.}, } @article {pmid38531462, year = {2024}, author = {Oliveira, NAS and Pinho, BR and Pinto, J and Guedes de Pinho, P and Oliveira, JMA}, title = {Edaravone counteracts redox and metabolic disruptions in an emerging zebrafish model of sporadic ALS.}, journal = {Free radical biology & medicine}, volume = {217}, number = {}, pages = {126-140}, doi = {10.1016/j.freeradbiomed.2024.03.016}, pmid = {38531462}, issn = {1873-4596}, mesh = {Animals ; Humans ; *Amyotrophic Lateral Sclerosis/genetics/metabolism ; Edaravone ; Zebrafish ; *Neurodegenerative Diseases ; Oxidation-Reduction ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease in which the death of motor neurons leads to loss of muscle function. Additionally, cognitive and circadian disruptions are common in ALS patients, contributing to disease progression and burden. Most ALS cases are sporadic, and environmental exposures contribute to their aetiology. However, animal models of these sporadic ALS cases are scarce. The small vertebrate zebrafish is a leading organism to model neurodegenerative diseases; previous studies have proposed bisphenol A (BPA) or β-methylamino-l-alanine (BMAA) exposure to model sporadic ALS in zebrafish, damaging motor neurons and altering motor responses. Here we characterise the face and predictive validity of sporadic ALS models, showing their potential for the mechanistic study of ALS drugs. We phenotypically characterise the BPA and BMAA-induced models, going beyond motor activity and motor axon morphology, to include circadian, redox, proteostasis, and metabolomic phenotypes, and assessing their predictive validity for ALS modelling. BPA or BMAA exposure induced concentration-dependent activity impairments. Also, exposure to BPA but not BMAA induced motor axonopathy and circadian alterations in zebrafish larvae. Our further study of the BPA model revealed loss of habituation to repetitive startles, increased oxidative damage, endoplasmic reticulum (ER) stress, and metabolome abnormalities. The BPA-induced model shows predictive validity, since the approved ALS drug edaravone counteracted BPA-induced motor phenotypes, ER stress, and metabolic disruptions. Overall, BPA exposure is a promising model of ALS-related redox and ER imbalances, contributing to fulfil an unmet need for validated sporadic ALS models.}, } @article {pmid38531340, year = {2024}, author = {Lee, KH and Kim, MH and Kim, J and Nam, HJ}, title = {Acupuncture for Tinnitus: A Scoping Review of Clinical Studies.}, journal = {Complementary medicine research}, volume = {31}, number = {3}, pages = {292-301}, pmid = {38531340}, issn = {2504-2106}, mesh = {Humans ; *Acupuncture Therapy/methods ; *Tinnitus/therapy ; Randomized Controlled Trials as Topic ; Acupuncture Points ; }, abstract = {BACKGROUND: Acupuncture treatment for tinnitus has received attention owing to its potential as an alternative to conventional treatment modalities. We conducted a scoping review to identify detailed information on acupuncture treatment methods used in clinical studies and to provide useful information for practitioners, patients, and researchers.

METHODS: MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), Embase, Oriental Medicine Advanced Searching Integrated System (OASIS), Korean Research Information Sharing Service (RISS), DataBase Periodical Information Academic (DBPIA), and the China National Knowledge Infrastructure (CNKI) were searched from their inception to December 2023. This review included single-arm trials, open-label randomized controlled trials (RCTs), and double-blind RCTs using needle-type acupuncture to treat tinnitus in English, Chinese, and Korean. We investigated basic and detailed information on the acupuncture treatment methods, assessment methods, and study outcomes. Network analysis was also conducted to evaluate the centrality between acupoints in the double-blind RCTs.

RESULTS: We included 106 articles. There were 11 single-arm trials, 90 open-label RCTs, and 5 double-blind RCTs. Most (89.6%) of these studies were conducted in China. Manual acupuncture was the most common type of acupuncture in treatment group. A total of 119 acupuncture points were used 1,138 times. The most frequently used acupoints were local points around the ear (TE17, GB2, SI19, and TE21). Both local and distant acupoints were used simultaneously in these studies. The treatment duration of 20-39 days, 10 to 19 sessions of treatment, the mean acupuncture duration of 30 min, needle diameter of 0.30 mm × 40 mm, and needling depth over 30 mm and less than 50 mm were confirmed as the most common.

CONCLUSION: These study outcomes will enable future acupuncture studies on tinnitus to perform more effective and standardized acupuncture treatments in selecting acupoints and procedures. Furthermore, the study has implications for informing clinicians and students about more impactful acupuncture strategies for addressing tinnitus.

UNLABELLED: HintergrundDie Anwendung von Akupunktur bei Tinnitus erhält seit einiger Zeit Aufmerksamkeit als potenzielle Alternative zu konventionellen Behandlungsmodalitäten. Wir führten einen Scoping-Review durch, um detaillierte Informationen zu den in klinischen Studien angewandten Akupunktur-Behandlungsmethoden zu sammeln und nützliche Informationen für Praktiker, Patienten und Forscher bereitzustellen.MethodenMEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), Embase, Oriental Medicine Advanced Searching Integrated System (OASIS), Korean Research Information Sharing Service (RISS), DataBase Periodical Information Academic (DBPIA) und die China National Knowledge Infrastructure (CNKI) wurden von ihrem jeweiligen Beginn bis Dezember 2023 durchsucht. In diese Übersichtsarbeit wurden einarmige Studien, offene, randomisierte, kontrollierte Studien (RCTs) sowie doppelt verblindete RCTs zu Nadel-Akupunktur zur Behandlung von Tinnitus in englischer, chinesischer und koreanischer Sprache einbezogen. Wir untersuchten grundlegende und detaillierte Informationen zu den Akupunktur-Behandlungsmethoden, Untersuchungsmethoden und Studienergebnissen. Außerdem wurden Netzwerkanalysen zur Beurteilung der Zentralität zwischen Akupunkten in den doppelt verblindeten RCTs durchgeführt.Ergebnisse106 Artikel wurden eingeschlossen. Sie behandelten 11 einarmige Studien, 90 offene RCTs und 5 doppelt verblindete RCTs. Die meisten (89,6%) dieser Studien waren in China durchgeführt worden. Manuelle Akupunktur war die häufigste Form der Akupunktur in den Behandlungsgruppen. 119 Akupunkturpunkte wurden insgesamt 1’138 Mal verwendet. Die am häufigsten verwendeten Akupunkte waren lokale Punkte im Bereich des Ohrs (TE17, GB2, SI19 und TE21). Jedoch wurden in den Studien lokale und entfernte Akupunkte gleichzeitig angewendet. Außerdem wurde festgestellt, dass die Behandlungsdauer am häufigsten 20 bis 39 Tage betrug, die Zahl der Sitzungen 10 bis 19, die mittlere Akupunkturdauer 30 Minuten, die Nadelgröße 0.30 mm × 40 mm und die Einstichtiefe zwischen 30 mm und weniger als 50 mm.SchlussfolgerungDiese Studienergebnisse bieten eine Grundlage für künftige Studien zu Akupunktur bei Tinnitus, um durch die Auswahl der Akupunkte und Verfahren wirksamere und standardisierte Akupunkturbehandlungen durchzuführen. Darüber hinaus hat die Studie Implikationen für die Aufklärung von Praktikern und Schülern über wirkungsvollere Akupunkturstrategien zur Behandlung von Tinnitus.}, } @article {pmid38528673, year = {2024}, author = {Howard, J and Mazanderani, F and Keenan, KF and Turner, MR and Locock, L}, title = {Fluctuating salience in those living with genetic risk of motor neuron disease: A qualitative interview study.}, journal = {Health expectations : an international journal of public participation in health care and health policy}, volume = {27}, number = {2}, pages = {e14024}, pmid = {38528673}, issn = {1369-7625}, support = {Locock/Sept19/941-794/MNDA_/Motor Neurone Disease Association/United Kingdom ; }, mesh = {Adult ; Child ; Humans ; *Motor Neuron Disease/genetics/diagnosis/psychology ; *Amyotrophic Lateral Sclerosis/diagnosis/pathology ; Qualitative Research ; Uncertainty ; Emotions ; }, abstract = {BACKGROUND: Motor neuron disease (MND) (also known as amyotrophic lateral sclerosis) is a life-limiting neurodegenerative condition. In up to 20% of people with MND, a pathogenic variant associated with autosomal dominant inheritance can be identified. Children of people carrying a pathogenic variant have a 50% chance of inheriting this and a higher, although harder to predict, chance of developing the disease compared to the general adult population. This paper explores the experience of living with the genetic risk of MND.

METHODS: We undertook a UK-based interview study with 35 individuals, including: 7 people living with genetically-mediated forms of MND; 24 asymptomatic relatives, the majority of whom had an increased risk of developing the disease; and 4 unrelated partners.

RESULTS: We explore how individuals make sense of genetic risk, unpacking the interplay between genetic knowledge, personal perception, experiences of the disease in the family, age and life stage and the implications that living with risk has for different aspects of their lives. We balance an emphasis on the emotional and psychological impact described by participants, with a recognition that the salience of risk fluctuates over time. Furthermore, we highlight the diverse strategies and approaches people employ to live well in the face of uncertainty and the complex ways they engage with the possibility of developing symptoms in the future. Finally, we outline the need for open-ended, tailored support and information provision.

CONCLUSIONS: Drawing on wider literature on genetic risk, we foreground how knowledge of MND risk can disrupt individuals' taken-for-granted assumptions on life and perceptions of the future, but also its contextuality, whereby its relevance becomes more prominent at critical junctures. This research has been used in the development of a public-facing resource on the healthtalk.org website.

People with experience of living with genetic risk were involved throughout the design and conduct of the study and advised on aspects including the topic guide, sampling and recruitment and the developing analysis. Two patient and public involvement contributors joined a formal advisory panel.}, } @article {pmid38527450, year = {2023}, author = {Cheong, I and Du, Y and Smith, G and Hua, J and Li, X and Pantelyat, A}, title = {Cerebral Tau Deposition in Comorbid Progressive Supranuclear Palsy and Amyotrophic Lateral Sclerosis: An [18F]-Flortaucipir and 7T MRI Study.}, journal = {Neuro-degenerative diseases}, volume = {23}, number = {3-4}, pages = {35-42}, pmid = {38527450}, issn = {1660-2862}, support = {K23 AG059891/AG/NIA NIH HHS/United States ; R01 AG059390/AG/NIA NIH HHS/United States ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnostic imaging/metabolism ; Brain/diagnostic imaging/metabolism ; *Carbolines ; *Magnetic Resonance Imaging/methods ; *Positron-Emission Tomography/methods ; *Supranuclear Palsy, Progressive/diagnostic imaging/metabolism ; *tau Proteins/metabolism ; }, abstract = {INTRODUCTION: Progressive supranuclear palsy (PSP) is a four-repeat tauopathy characterized by multiple clinicopathologic subtypes. Advanced neuroimaging techniques have shown an early ability to distinguish PSP subtypes noninvasively for improved diagnosis. This study utilized tau PET imaging and MRI techniques at 7T to determine the neuroimaging profile of a participant with comorbid PSP and amyotrophic lateral sclerosis (ALS).

METHOD: [18F]-flortaucipir PET imaging was performed on one participant with PSP-ALS, one participant with typical PSP (Richardson's syndrome; PSP-RS), and 15 healthy control volunteers. Standardized uptake value ratio (SUVR) in each brain region was compared between PSP participants and controls. Quantitative susceptibility mapping (QSM) and inflow-based vascular-space occupancy MRI at 7T were performed on the two PSP participants and on two age-matched healthy controls to evaluate for differences in regional brain iron content and arteriolar cerebral blood volume (CBVa), respectively.

RESULTS: In the participant with PSP-ALS, the precentral gyrus demonstrated the highest [18F]-flortaucipir uptake of all brain regions relative to controls (z-score 1.94). In the participant with PSP-RS, [18F]-flortaucipir uptake relative to controls was highest in subcortical regions, including the pallidum, thalamus, hippocampus, and brainstem (z-scores 1.08, 1.41, 1.49, 1.32, respectively). Susceptibility values as a measure of brain iron content were higher in the globus pallidus and substantia nigra than in the midbrain and pons in each participant, regardless of group. CBVa values tended to be higher in the subcortical gray matter in PSP participants than in controls, although large measurement variability was noted in controls across multiple regions.

CONCLUSION: In vivo tau PET imaging of an individual with PSP-ALS overlap demonstrated increased tau burden in the motor cortex that was not observed in PSP-RS or control participants. Consistent with prior PET studies, tau burden in PSP-RS was mainly observed in subcortical regions, including the brainstem and basal ganglia. QSM data suggest that off-target binding to iron may account for some but not all of the increased [18F]-flortaucipir uptake in the basal ganglia in PSP-RS. These findings support existing evidence that tau PET imaging can distinguish among PSP subtypes by detecting distinct regional patterns of tau deposition in the brain. Larger studies are needed to determine whether CBVa is sensitive to changes in brain microvasculature in PSP.}, } @article {pmid38526287, year = {2024}, author = {Chen, W and Jiang, S and Li, S and Li, C and Xu, R}, title = {OSMR is a potential driver of inflammation in amyotrophic lateral sclerosis.}, journal = {Neural regeneration research}, volume = {19}, number = {11}, pages = {2513-2521}, pmid = {38526287}, issn = {1673-5374}, abstract = {JOURNAL/nrgr/04.03/01300535-202419110-00031/figure1/v/2024-03-08T184507Z/r/image-tiff Amyotrophic lateral sclerosis is a neurodegenerative disease, and the molecular mechanism underlying its pathology remains poorly understood. However, inflammation is known to play an important role in the development of this condition. To identify driver genes that affect the inflammatory response in amyotrophic lateral sclerosis, as well as potential treatment targets, it is crucial to analyze brain tissue samples from patients with both sporadic amyotrophic lateral sclerosis and C9orf72-related amyotrophic lateral sclerosis. Therefore, in this study we used a network-driven gene analysis tool, NetBID2.0, which is based on SJARACNe, a scalable algorithm for the reconstruction of accurate cellular networks, to experimentally analyze sequencing data from patients with sporadic amyotrophic lateral sclerosis. The results showed that the OSMR gene is pathogenic in amyotrophic lateral sclerosis and participates in the progression of amyotrophic lateral sclerosis by mediating the neuroinflammatory response. Furthermore, there were differences in OSMR activity and expression between patients with sporadic amyotrophic lateral sclerosis and those with C9orf72-related amyotrophic lateral sclerosis. These findings suggest that OSMR may be a diagnostic and prognostic marker for amyotrophic lateral sclerosis.}, } @article {pmid38525704, year = {2024}, author = {Shirai, R and Yamauchi, J}, title = {Emerging Evidence of Golgi Stress Signaling for Neuropathies.}, journal = {Neurology international}, volume = {16}, number = {2}, pages = {334-348}, pmid = {38525704}, issn = {2035-8385}, abstract = {The Golgi apparatus is an intracellular organelle that modifies cargo, which is transported extracellularly through the nucleus, endoplasmic reticulum, and plasma membrane in order. First, the general function of the Golgi is reviewed and, then, Golgi stress signaling is discussed. In addition to the six main Golgi signaling pathways, two pathways that have been increasingly reported in recent years are described in this review. The focus then shifts to neurological disorders, examining Golgi stress reported in major neurological disorders, such as Alzheimer's disease, Parkinson's disease, and Huntington's disease. The review also encompasses findings related to other diseases, including hypomyelinating leukodystrophy, frontotemporal spectrum disorder/amyotrophic lateral sclerosis, microcephaly, Wilson's disease, and prion disease. Most of these neurological disorders cause Golgi fragmentation and Golgi stress. As a result, strong signals may act to induce apoptosis.}, } @article {pmid38525545, year = {2024}, author = {Alpert, EA and Assaf, J and Nama, A and Pliner, R and Jaffe, E}, title = {Secondary Ambulance Transfers During the Mass-Casualty Terrorist Attack in Israel on October 7, 2023.}, journal = {Prehospital and disaster medicine}, volume = {39}, number = {2}, pages = {224-227}, doi = {10.1017/S1049023X24000153}, pmid = {38525545}, issn = {1945-1938}, mesh = {Israel ; Humans ; *Mass Casualty Incidents ; *Ambulances ; *Terrorism ; Emergency Medical Services/organization & administration ; Patient Transfer ; }, abstract = {On October 7, 2023, Israel experienced the worst terror attack in its history - 1,200 people were killed, 239 people were taken hostage, and 1,455 people were wounded. This mass-casualty event (MCE) was more specifically a mega terrorist attack. Due to the overwhelming number of victims who arrived at the two closest hospitals, it became necessary to implement secondary transfers to centers in other areas of the country. Historically, secondary transfer has been implemented in MCEs but usually for the transfer of critical patients from a Level 2 or Level 3 Trauma Center to a Level 1 Center. Magen David Adom (MDA), Israel's National Emergency Pre-Hospital Medical Organization, is designated by the Health Ministry as the incident command at any MCE. On October 7, in addition to the primary transport of victims by ambulance to hospitals throughout Israel, they secondarily transported patients from the two closest hospitals - the Soroka Medical Center (SMC; Level 1 Trauma Center) in Beersheba and the Barzilai Medical Center (BMC; Level 2 Trauma Center) in Ashkelon. Secondary transport began five hours after the event started and continued for approximately 12 hours. During this time, the terrorist infiltration was still on-going. Soroka received 650 victims and secondarily transferred 26, including five in Advanced Life Support (ALS) ambulances. Barzilai received 372 and secondarily transferred 38. These coordinated secondary transfers helped relieve the overwhelmed primary hospitals and are an essential component of any MCE strategy.}, } @article {pmid38525350, year = {2024}, author = {Gosik, R and Caldara, R and Toševski, I and Skuhrovec, J}, title = {Description of immature stages of Rhinusa species (Coleoptera, Curculionidae, Mecinini) with a focus on diagnostic morphological characters at the species and genus levels.}, journal = {ZooKeys}, volume = {1195}, number = {}, pages = {1-94}, pmid = {38525350}, issn = {1313-2989}, abstract = {The mature larvae of the following fourteen Rhinusa species are described and illustrated: Rhinusaantirrhini (Paykull, 1800), R.asellus (Gravenhorst, 1807), R.collina (Gyllenhal, 1813), R.eversmanni (Rosenschoeld, 1838), R.florum (Rubsaamen, 1895), R.herbarum (H. Brisout de Barneville, 1862), R.incana (Kirsch, 1881), R.linariae (Panzer, 1796), R.melas (Boheman, 1838), R.neta (Germar, 1821), R.pilosa (Gyllenhal, 1838), R.rara Toševski & Caldara, 2015, R.tetra (Fabricius, 1792), and R.vestita (Germar, 1821). The pupae of thirteen of them (except R.incana) were also described. The comparison of larval morphological characters and plant preferences provides evidence supporting the existence of different species groups previously established according to a phylogenetic analysis based on adult morphological characters. The following diagnostic attributes distinguishing the genus Rhinusa are highlighted. For the larvae: (1) pronotal shield indistinct; (2) thoracic prodorsal fold small or even vestigial; (3) abdominal postdorsal folds (especially of segments III-VII) high or even in the form of conical protuberances; (4) cuticle of abdominal segments densely covered with asperities; (5) cuticle without dark spots or dark pigmentation; (6) head suboval, rarely round; (7) labrum usually with 2 als; (8) des1 short or absent, rarely elongated; and (9) fs1-3 usually absent or minute. For the pupae: (1) body stout; (2) head protuberances always present; (3) pronotal protuberances (if present), separated at bases of the pronotum, always wider than higher; (4) abdominal protuberance usually present, wide or round; (5) femora usually with a single fes; and (6) urogomphi short or vestigial. Keys to the larvae and pupae described here are provided. All the characters used for identification are illustrated by photographs or drawings. Biological and distribution data, including new information, are provided for all the species studied.}, } @article {pmid38524582, year = {2024}, author = {Yamamoto, Y and Fujita, K and Yamazaki, H and Haji, S and Osaki, Y and Izumi, Y}, title = {Constipation in patients with motor neuron disease: A retrospective longitudinal study.}, journal = {Heliyon}, volume = {10}, number = {6}, pages = {e27951}, pmid = {38524582}, issn = {2405-8440}, abstract = {BACKGROUND: Constipation has been recently recognized as a complication associated with motor and autonomic dysfunction in patients with motor neuron disease (MND), typified by amyotrophic lateral sclerosis (ALS). However, the long-term characteristics of constipation remain unclear in patients with MND. We longitudinally investigated the prevalence and risk factors of constipation in a consecutive cohort of patients with MND.

METHODS: Data from Japanese patients with MND enrolled in a single-center registry from June 2017 to December 2021 were retrospectively investigated. The diagnosis of ALS was based on the updated Awaji criteria, and other MND subtypes were also included. The presence or absence of constipation symptoms was determined by referring to the Rome III criteria. The clinical backgrounds and symptoms of patients with and without constipation were compared.

RESULTS: Among 155 consecutive patients (female, 63; age, 66.5 ± 12.4 years), 30.3% had constipation at diagnosis and 52.9% after a median follow-up of 18 months. Univariate analysis showed that female sex, use of tracheostomy and invasive ventilation, and delivery of enteral nutrition were more frequent in the constipation group. The Revised Amyotrophic Lateral Sclerosis Functional Rating Scale score was significantly lower in the constipation group, especially for the sub-items related to physical motor function. Multivariate analysis showed that the use of enteral nutrition was an independent risk of constipation, with an odds ratio of 3.69 (95% CI, 1.49-9.17; p = 0.005).

CONCLUSION: Constipation had a high prevalence in patients with MND with impaired motor function. Controlling defecation is important in patients with MND, especially during enteral nutrition.}, } @article {pmid38524510, year = {2024}, author = {Liu, YX and Xu, Y}, title = {Enhancing competency of clinical research nurses: A comprehensive training and evaluation framework.}, journal = {World journal of clinical cases}, volume = {12}, number = {7}, pages = {1378-1381}, pmid = {38524510}, issn = {2307-8960}, abstract = {The Sun et al's training program for clinical research nurses (CRNs) in the World Journal of Clinical Cases is a comprehensive and scientific approach. It includes structured frameworks for CRN training, aiming to improve CRN competency. This program emphasizes practical abilities, updates training content, and improves evaluation methods. The cultivation of CRN talents focuses on enhancing the training system, establishing a multifaceted evaluation framework, and continuously refining the training programs. Regular feedback and evaluation are essential to improve CRNs' competency in practical settings.}, } @article {pmid38524401, year = {2024}, author = {Pota, V and Sansone, P and De Sarno, S and Aurilio, C and Coppolino, F and Barbarisi, M and Barbato, F and Fiore, M and Cosenza, G and Passavanti, MB and Pace, MC}, title = {Amyotrophic Lateral Sclerosis and Pain: A Narrative Review from Pain Assessment to Therapy.}, journal = {Behavioural neurology}, volume = {2024}, number = {}, pages = {1228194}, pmid = {38524401}, issn = {1875-8584}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/complications ; Pain Measurement ; Quality of Life ; *Neurodegenerative Diseases/complications ; Pain/drug therapy ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is the most frequent neurodegenerative disease of the motor system that affects upper and lower motor neurons, leading to progressive muscle weakness, spasticity, atrophy, and respiratory failure, with a life expectancy of 2-5 years after symptom onset. In addition to motor symptoms, patients with ALS have a multitude of nonmotor symptoms; in fact, it is currently considered a multisystem disease. The purpose of our narrative review is to evaluate the different types of pain, the correlation between pain and the disease's stages, the pain assessment tools in ALS patients, and the available therapies focusing above all on the benefits of cannabis use. Pain is an underestimated and undertreated symptom that, in the last few years, has received more attention from research because it has a strong impact on the quality of life of these patients. The prevalence of pain is between 15% and 85% of ALS patients, and the studies on the type and intensity of pain are controversial. The absence of pain assessment tools validated in the ALS population and the dissimilar study designs influence the knowledge of ALS pain and consequently the pharmacological therapy. Several studies suggest that ALS is associated with changes in the endocannabinoid system, and the use of cannabis could slow the disease progression due to its neuroprotective action and act on pain, spasticity, cramps, sialorrhea, and depression. Our research has shown high patients' satisfaction with the use of cannabis for the treatment of spasticity and related pain. However, especially due to the ethical problems and the lack of interest of pharmaceutical companies, further studies are needed to ensure the most appropriate care for ALS patients.}, } @article {pmid38522911, year = {2024}, author = {Urushitani, M and Warita, H and Atsuta, N and Izumi, Y and Kano, O and Shimizu, T and Nakayama, Y and Narita, Y and Nodera, H and Fujita, T and Mizoguchi, K and Morita, M and Aoki, M}, title = {The clinical practice guideline for the management of amyotrophic lateral sclerosis in Japan-update 2023.}, journal = {Rinsho shinkeigaku = Clinical neurology}, volume = {64}, number = {4}, pages = {252-271}, doi = {10.5692/clinicalneurol.cn-001946}, pmid = {38522911}, issn = {1882-0654}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy/diagnosis ; Disease Progression ; Evidence-Based Medicine ; Japan ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is an adult-onset intractable motor neuron disease characterized by selective degeneration of cortical neurons in the frontotemporal lobe and motor neurons in the brainstem and spinal cord. Impairment of these neural networks causes progressive muscle atrophy and weakness that spreads throughout the body, resulting in life-threatening bulbar palsy and respiratory muscle paralysis. However, no therapeutic strategy has yet been established to halt ALS progression. Although evidence for clinical practice in ALS remains insufficient, novel research findings have steadily accumulated in recent years. To provide updated evidence-based or expert consensus recommendations for the diagnosis and management of ALS, the ALS Clinical Practice Guideline Development Committee, approved by the Japanese Society of Neurology, revised and published the Japanese clinical practice guidelines for the management of ALS in 2023. In this guideline, disease-modifying therapies that have accumulated evidence from randomized controlled trials were defined as "Clinical Questions," in which the level of evidence was determined by systematic reviews. In contrast, "Questions and Answers" were defined as issues of clinically important but insufficient evidence, according to reports of a small number of cases, observational studies, and expert opinions. Based on a literature search performed in February 2022, recommendations were reached by consensus, determined by an independent panel, reviewed by external reviewers, and submitted for public comments by Japanese Society of Neurology members before publication. In this article, we summarize the revised Japanese guidelines for ALS, highlighting the regional and cultural diversity of care processes and decision-making. The guidelines cover a broad range of essential topics such as etiology, diagnostic criteria, disease monitoring and treatments, management of symptoms, respiration, rehabilitation, nutrition, metabolism, patient instructions, and various types of care support. We believe that this summary will help improve the daily clinical practice for individuals living with ALS and their caregivers.}, } @article {pmid38522733, year = {2024}, author = {Rupp, D and Heuser, N and Sassen, MC and Betz, S and Volberg, C and Glass, S}, title = {Resuscitation (un-)wanted: Does anyone care? A retrospective real data analysis.}, journal = {Resuscitation}, volume = {198}, number = {}, pages = {110189}, doi = {10.1016/j.resuscitation.2024.110189}, pmid = {38522733}, issn = {1873-1570}, mesh = {Humans ; Retrospective Studies ; *Out-of-Hospital Cardiac Arrest/therapy ; Male ; Female ; Aged ; Aged, 80 and over ; *Cardiopulmonary Resuscitation/statistics & numerical data/methods ; *Emergency Medical Services/statistics & numerical data/methods ; Germany ; *Resuscitation Orders ; Middle Aged ; Advance Directives/statistics & numerical data ; }, abstract = {BACKGROUND AND OBJECTIVES: In case of out-of-hospital cardiac arrest (OHCA) personnel of the emergency medical services (EMS) are regularly confronted with advanced directives (AD) and do-not-attempt-resuscitation (DNACPR) orders. The authors conducted a retrospective analysis of EMS operation protocols to examine the prevalence of DNACPR in case of OHCA and the influence of a presented DNACPR on CPR-duration, performed Advanced-Life-Support (ALS) measures and decision making.

MATERIALS AND METHODS: Retrospective analysis of prehospital medical documentation of all resuscitation incidents in a German county with 250,000 inhabitants from 1 January 2016 to 31 December 2022. Combined with data from the structured CPR team-feedback database patients characteristics, measures and course of the CPR were analysed. Statistic testing with significance level p < 0.05.

RESULTS: In total n = 1,474 CPR events were analysed. Patients with DNACPR vs. no DNACPR: n = 263 (17.8%) vs. n = 1,211 (82.2%). Age: 80.0 ± 10.3 years vs. 68.0 ± 13.9 years; p < 0.001. Patients with ASA-status III/IV: n = 214 (81.3%) vs. n = 616 (50.9%); p < 0.001. Initial layperson-CPR: n = 148 (56.3%) vs. n = 647 (55.7%); p = 0.40. Airway management: n = 185 (70.3%) vs. n = 1,069 (88.3%); p < 0.001. With DNACPR CPR-duration initiated layperson-CPR vs. no layperson-CPR: 19:14 min (10:43-25:55 min) vs. 12:40 min (06:35-20:03 min); p < 0.001.

CONCLUSION: In case of CPR EMS-personnel are often confronted with DNACPR-orders. Patients are older and have more previous diseases than patients without DNACPR. Initiated layperson-CPR might lead to misinterpretation of patients will with impact on CPR-duration and unwanted measures. Awareness of this issue should be created through measures such as training programs in particular to train staff in the interpretation and legal admissibility of ADs.}, } @article {pmid38522514, year = {2024}, author = {Pokrishevsky, E and DuVal, MG and McAlary, L and Louadi, S and Pozzi, S and Roman, A and Plotkin, SS and Dijkstra, A and Julien, JP and Allison, WT and Cashman, NR}, title = {Tryptophan residues in TDP-43 and SOD1 modulate the cross-seeding and toxicity of SOD1.}, journal = {The Journal of biological chemistry}, volume = {300}, number = {5}, pages = {107207}, pmid = {38522514}, issn = {1083-351X}, mesh = {Humans ; *Tryptophan/metabolism ; *Zebrafish ; Animals ; *Superoxide Dismutase-1/metabolism/genetics/chemistry ; *DNA-Binding Proteins/metabolism/genetics ; *Amyotrophic Lateral Sclerosis/metabolism/genetics/pathology ; Protein Folding ; Motor Neurons/metabolism/pathology ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease of motor neurons. Neuronal superoxide dismutase-1 (SOD1) inclusion bodies are characteristic of familial ALS with SOD1 mutations, while a hallmark of sporadic ALS is inclusions containing aggregated WT TAR DNA-binding protein 43 (TDP-43). We show here that co-expression of mutant or WT TDP-43 with SOD1 leads to misfolding of endogenous SOD1 and aggregation of SOD1 reporter protein SOD1[G85R]-GFP in human cell cultures and promotes synergistic axonopathy in zebrafish. Intriguingly, this pathological interaction is modulated by natively solvent-exposed tryptophans in SOD1 (tryptophan-32) and TDP-43 RNA-recognition motif RRM1 (tryptophan-172), in concert with natively sequestered TDP-43 N-terminal domain tryptophan-68. TDP-43 RRM1 intrabodies reduce WT SOD1 misfolding in human cell cultures, via blocking tryptophan-172. Tryptophan-68 becomes antibody-accessible in aggregated TDP-43 in sporadic ALS motor neurons and cell culture. 5-fluorouridine inhibits TDP-43-induced G85R-GFP SOD1 aggregation in human cell cultures and ameliorates axonopathy in zebrafish, via its interaction with SOD1 tryptophan-32. Collectively, our results establish a novel and potentially druggable tryptophan-mediated mechanism whereby two principal ALS disease effector proteins might directly interact in disease.}, } @article {pmid38522245, year = {2024}, author = {Geronimo, A and Simmons, Z}, title = {Remote pulmonary function testing allows for early identification of need for non-invasive ventilation in a subset of persons with ALS.}, journal = {Journal of the neurological sciences}, volume = {459}, number = {}, pages = {122971}, doi = {10.1016/j.jns.2024.122971}, pmid = {38522245}, issn = {1878-5883}, support = {UL1 TR002014/TR/NCATS NIH HHS/United States ; }, mesh = {Humans ; *Noninvasive Ventilation ; *Amyotrophic Lateral Sclerosis/diagnosis/therapy ; *Respiratory Insufficiency/diagnosis/etiology/therapy ; Respiratory Function Tests ; Physical Examination ; }, abstract = {The traditional ALS multidisciplinary clinical practice of quarterly respiratory assessment may leave some individuals in danger of developing untreated respiratory insufficiency between visits or beginning non-invasive ventilation (NIV) later than would be optimal. Remote, or home-based, pulmonary function testing (rPFT) allows patients with ALS to perform regular respiratory testing at more frequent intervals in the home. The aim of this study was to determine the clinical benefit of weekly rPFT compared to standard, quarterly in-clinic respiratory assessments: the number of individuals with earlier identification of NIV need, the magnitude of this advance notice, and the individual factors predicting benefit. Participants with ALS (n = 39) completed rPFT training via telemedicine and then completed one year of weekly self-guided assessments in the home. Over this period, 17 individuals exhibited remotely-measured FVC dropping below 50% of predicted, the value often used for recommendation of NIV initiation. In 13 individuals with clinical detection of this event, the median and range of advance notice of need for NIV was 53 (-61-294) days. Prescription of NIV occurred for 21 individuals on the study, six of whom began NIV as a result of remote testing, prior to indication of need as determined by in-person assessments. Weekly home assessments appeared to be of greatest clinical value in a subset of patients with low baseline respiratory test values and rapid respiratory decline. This has potential implications for clinical management of ALS as well as the conduct of clinical trials that rely on respiratory endpoints.}, } @article {pmid38522244, year = {2024}, author = {Swash, M}, title = {Timing initiation of non-invasive ventilation in management of ALS.}, journal = {Journal of the neurological sciences}, volume = {459}, number = {}, pages = {122972}, doi = {10.1016/j.jns.2024.122972}, pmid = {38522244}, issn = {1878-5883}, mesh = {Humans ; *Noninvasive Ventilation ; *Amyotrophic Lateral Sclerosis/therapy ; *Respiratory Insufficiency ; }, } @article {pmid38521615, year = {2024}, author = {Ramos, R and Kaouk, J}, title = {Reply to Alessandro Guercio, Antonio Franco, Elisa Mancini, et al's Letter to the Editor re: Roxana Ramos, Ethan Ferguson, Mahmoud Abou Zeinab, et al. Single-port Transvesical Robot-assisted Simple Prostatectomy: Surgical Technique and Clinical Outcomes. Eur Urol. 2024;85:445-456.}, journal = {European urology}, volume = {85}, number = {6}, pages = {e171-e172}, doi = {10.1016/j.eururo.2024.03.020}, pmid = {38521615}, issn = {1873-7560}, mesh = {Humans ; Male ; *Prostatectomy/methods ; *Robotic Surgical Procedures ; Treatment Outcome ; }, } @article {pmid38521060, year = {2024}, author = {Pineda, SS and Lee, H and Ulloa-Navas, MJ and Linville, RM and Garcia, FJ and Galani, K and Engelberg-Cook, E and Castanedes, MC and Fitzwalter, BE and Pregent, LJ and Gardashli, ME and DeTure, M and Vera-Garcia, DV and Hucke, ATS and Oskarsson, BE and Murray, ME and Dickson, DW and Heiman, M and Belzil, VV and Kellis, M}, title = {Single-cell dissection of the human motor and prefrontal cortices in ALS and FTLD.}, journal = {Cell}, volume = {187}, number = {8}, pages = {1971-1989.e16}, pmid = {38521060}, issn = {1097-4172}, support = {R35 NS127327/NS/NINDS NIH HHS/United States ; R01 NS127187/NS/NINDS NIH HHS/United States ; F32 NS128067/NS/NINDS NIH HHS/United States ; T32 EB019940/EB/NIBIB NIH HHS/United States ; R01 AG067151/AG/NIA NIH HHS/United States ; U01 NS110453/NS/NINDS NIH HHS/United States ; R56 AG067151/AG/NIA NIH HHS/United States ; }, mesh = {Animals ; Humans ; Mice ; *Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology ; Frontotemporal Dementia/genetics ; *Frontotemporal Lobar Degeneration/genetics/metabolism/pathology ; Gene Expression Profiling ; Neurons/metabolism ; *Prefrontal Cortex/metabolism/pathology ; Single-Cell Gene Expression Analysis ; }, abstract = {Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) share many clinical, pathological, and genetic features, but a detailed understanding of their associated transcriptional alterations across vulnerable cortical cell types is lacking. Here, we report a high-resolution, comparative single-cell molecular atlas of the human primary motor and dorsolateral prefrontal cortices and their transcriptional alterations in sporadic and familial ALS and FTLD. By integrating transcriptional and genetic information, we identify known and previously unidentified vulnerable populations in cortical layer 5 and show that ALS- and FTLD-implicated motor and spindle neurons possess a virtually indistinguishable molecular identity. We implicate potential disease mechanisms affecting these cell types as well as non-neuronal drivers of pathogenesis. Finally, we show that neuron loss in cortical layer 5 tracks more closely with transcriptional identity rather than cellular morphology and extends beyond previously reported vulnerable cell types.}, } @article {pmid38933502, year = {2024}, author = {Chen, BR and Wu, T and Chen, TH and Wang, Y}, title = {Neuroimmune interactions and their roles in neurodegenerative diseases.}, journal = {Fundamental research}, volume = {4}, number = {2}, pages = {251-261}, pmid = {38933502}, issn = {2667-3258}, abstract = {The nervous system possesses bidirectional, sophisticated and delicate communications with the immune system. These neuroimmune interactions play a vitally important role in the initiation and development of many disorders, especially neurodegenerative diseases. Although scientific advancements have made tremendous progress in this field during the last few years, neuroimmune communications are still far from being elucidated. By organizing recent research, in this review, we discuss the local and intersystem neuroimmune interactions and their roles in Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis. Unveiling these will help us gain a better understanding of the process of interplay inside the body and how the organism maintains homeostasis. It will also facilitate a view of the diseases from a holistic, pluralistic and interconnected perspective, thus providing a basis of developing novel and effective methods to diagnose, intervene and treat diseases.}, } @article {pmid39086676, year = {2023}, author = {Stoklund Dittlau, K and Van Den Bosch, L}, title = {Why should we care about astrocytes in a motor neuron disease?.}, journal = {Frontiers in molecular medicine}, volume = {3}, number = {}, pages = {1047540}, pmid = {39086676}, issn = {2674-0095}, abstract = {Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disease in adults, causing progressive degeneration of motor neurons, which results in muscle atrophy, respiratory failure and ultimately death of the patients. The pathogenesis of ALS is complex, and extensive efforts have focused on unravelling the underlying molecular mechanisms with a large emphasis on the dying motor neurons. However, a recent shift in focus towards the supporting glial population has revealed a large contribution and influence in ALS, which stresses the need to explore this area in more detail. Especially studies into astrocytes, the residential homeostatic supporter cells of neurons, have revealed a remarkable astrocytic dysfunction in ALS, and therefore could present a target for new and promising therapeutic entry points. In this review, we provide an overview of general astrocyte function and summarize the current literature on the role of astrocytes in ALS by categorizing the potentially underlying molecular mechanisms. We discuss the current efforts in astrocyte-targeted therapy, and highlight the potential and shortcomings of available models.}, } @article {pmid38933387, year = {2022}, author = {Li, X and Lu, S and Lu, B and Sun, X}, title = {Optogenetic control of GGGGCC repeat-containing RNA phase transition.}, journal = {Fundamental research}, volume = {2}, number = {6}, pages = {843-850}, pmid = {38933387}, issn = {2667-3258}, abstract = {The GGGGCC (G4C2) hexanucleotide repeat expansion in the C9ORF72 gene is a major cause of both hereditary amyotrophic lateral sclerosis and familial frontotemporal dementia. Recent studies have shown that G4C2 hexanucleotide repeat-containing RNA transcripts ((G4C2)n RNA) could go through liquid-liquid phase separation to form RNA foci, which may elicit neurodegeneration. However, the direct causality between these abnormal RNA foci and neuronal toxicity remains to be demonstrated. Here we introduce an optogenetic control system that can induce the assembly and phase separation of (G4C2)n RNA foci with blue light illumination in human cells, by fusing a specific (G4C2)n RNA binding protein as the linker domain to Cry2, a protein that oligomerizes in response to blue light. Our results demonstrate that a higher number of G4C2 repeats have the potential to be induced into more RNA foci in the cells. Both spontaneous and induced RNA foci display liquid-like properties according to FRAP measurements. Computational simulation shows strong consistency with the experimental results and supports the effect of our system to promote the propensity of (G4C2)n RNA towards phase separation. This system can thus be used to investigate whether (G4C2)n RNA foci would disrupt normal cellular processes and lead to pathological phenotypes relevant to repeat expansion disorders.}, } @article {pmid38715858, year = {2021}, author = {Gupta, S and Sharma, U}, title = {Metabolomics of neurological disorders in India.}, journal = {Analytical science advances}, volume = {2}, number = {11-12}, pages = {594-610}, pmid = {38715858}, issn = {2628-5452}, abstract = {Metabolomics is the comprehensive study of the metabolome and its alterations within biological fluids and tissues. Over the years, applications of metabolomics have been explored in several areas, including personalised medicine in diseases, metabolome-wide association studies (MWAS), pharmacometabolomics and in combination with other branches of omics such as proteomics, transcriptomics and genomics. Mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopy are the major analytical techniques widely employed in metabolomics. In addition, MS is coupled with chromatography techniques like gas chromatography (GC) and liquid chromatography (LC) to separate metabolites before analysis. These analytical techniques have made possible identification and quantification of large numbers of metabolites, encompassing characterization of diseases and facilitating a systematic and rational therapeutic strategy based on metabolic patterns. In recent years, the metabolomics approach has been used to obtain a deeper insight into the underlying biochemistry of neurodegenerative disorders and the discovery of biomarkers of clinical implications. The current review mainly focuses on an Indian perspective of metabolomics for the identification of metabolites and metabolic alterations serving as potential diagnostic biomarkers for neurological diseases including acute spinal cord injury, amyotrophic lateral sclerosis, tethered cord syndrome, spina bifida, stroke, Parkinson's disease, glioblastoma and neurological disorders with inborn errors of metabolism.}, } @article {pmid38520939, year = {2024}, author = {Ko, S and Yamasaki, R and Okui, T and Shiraishi, W and Watanabe, M and Hashimoto, Y and Kobayakawa, Y and Kusunoki, S and Kira, JI and Isobe, N}, title = {A nationwide survey of facial onset sensory and motor neuronopathy in Japan.}, journal = {Journal of the neurological sciences}, volume = {459}, number = {}, pages = {122957}, doi = {10.1016/j.jns.2024.122957}, pmid = {38520939}, issn = {1878-5883}, mesh = {Humans ; Japan/epidemiology ; *Amyotrophic Lateral Sclerosis ; Neurologic Examination ; Face ; }, abstract = {The epidemiology and etiology of facial onset sensory and motor neuronopathy (FOSMN), a rare syndrome that initiates with facial sensory disturbances followed by bulbar symptoms, remain unknown. To estimate the prevalence of FOSMN in Japan and establish the characteristics of this disease, we conducted a nationwide epidemiological survey. In the primary survey, we received answers from 604 facilities (49.8%), leading to an estimated number of 35.8 (95% confidential interval: 21.5-50.2) FOSMN cases in Japan. The secondary survey collected detailed clinical and laboratory data from 21 cases. Decreased or absent corneal and pharyngeal reflexes were present in over 85% of the cases. Electrophysiological analyses detected blink reflex test abnormalities in 94.1% of the examined cases. Immunotherapy was administered in 81% of cases and all patients received intravenous immunoglobulin. Among them, 35.3% were judged to have temporary beneficial effects evaluated by the physicians in charge. Immunotherapy tended to be effective in the early stage of disease. The spreading pattern of motor and sensory symptoms differed between cases and the characteristics of the motor-dominant and sensory-dominant cases were distinct. Cases with motor-dominant progression appeared to mimic amyotrophic lateral sclerosis. This is the first nationwide epidemiological survey of FOSMN in Japan. The clinical course of FOSMN is highly variable and motor-dominant cases developed a more severe condition than other types of cases. Because clinical interventions tend to be effective in the early phase of the disease, an early diagnosis is desirable.}, } @article {pmid38519870, year = {2024}, author = {Genuis, SK and Luth, W and Magnussen, C and Vande Velde, C and Taylor, D and , and Johnston, WS}, title = {Patient engagement in research: lessons learned from CAPTURE ALS, a longitudinal observational ALS study.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {25}, number = {5-6}, pages = {634-643}, doi = {10.1080/21678421.2024.2328599}, pmid = {38519870}, issn = {2167-9223}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/psychology ; Longitudinal Studies ; *Patient Participation/psychology/statistics & numerical data ; Canada/epidemiology ; Male ; Biomedical Research ; Female ; }, abstract = {OBJECTIVE: There are compelling ethical and practical reasons for patient engagement in research (PEIR), however, evidence for best practices remains limited. We investigated PEIR as implemented in CAPTURE ALS, a longitudinal observational study, from study inception through the first 2.5 years of operations.

METHODS: Data were drawn from three engagement initiatives: a community-led letter-writing campaign; consultation with patient and caregiver focus groups; and a study-embedded 'participant partner advisory council' (PPAC). Data were derived retrospectively from study documentation. We used the International Association of Public Participation (IAP2) participation spectrum as a framework for investigation.

RESULTS: 2401 letters from community members to the Canadian government affirmed study objectives and advocated for funding. Feedback from focus group consultation influenced study design and supported the study's data-sharing plan. PPAC collaboration shaped all aspects of the study. Contributions included: co-creation of governance documents, input on study protocols and public-facing communication, and development of engagement webinars for study participants and feedback surveys. Effective communication practices fostered collaboration and helped avoid tokenistic engagement. CAPTURE ALS encompassed all IAP2 participation levels.

CONCLUSIONS: CAPTURE ALS was shaped by meaningful engagement initiatives over the course of the study. Lessons learned included: begin early and embed PEIR within research; build relationships and foster mutual learning; be flexible, open to adaptation, and seek diversity. Primary challenges included funding for early implementation, time needed to maintain relationships, and attrition due to disease progression. All IAP2 participation levels contributed to meaningful PEIR. 'Empowerment' was demonstrated through advocacy.}, } @article {pmid38519722, year = {2024}, author = {Gowda, VK and Babu, S and Kinhal, U and Srinivasan, VM}, title = {Amyotrophic Lateral Sclerosis due to ALS2 Pathogenic Variant Masquerading as Cerebral Palsy: Authors' Reply.}, journal = {Indian journal of pediatrics}, volume = {91}, number = {9}, pages = {989}, pmid = {38519722}, issn = {0973-7693}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/genetics ; *Cerebral Palsy/diagnosis ; Diagnosis, Differential ; }, } @article {pmid38517792, year = {2024}, author = {Calderón-Garcidueñas, L and Ayala, A and Mukherjee, PS}, title = {2024 United States Elections: Air Pollution, Neurodegeneration, Neuropsychiatric, and Neurodevelopmental Disorders. Who Cares?.}, journal = {Journal of Alzheimer's disease : JAD}, volume = {98}, number = {4}, pages = {1277-1282}, pmid = {38517792}, issn = {1875-8908}, mesh = {Humans ; United States/epidemiology ; Adult ; *Air Pollutants/adverse effects ; *Air Pollution/adverse effects/analysis ; Particulate Matter ; *Alzheimer Disease ; *Neurodevelopmental Disorders/epidemiology/etiology ; }, abstract = {Air pollution exposures ought to be of significant interest for the United States (US) public as health issues will play a role in the 2024 elections. Citizens are not aware of the harmful brain impact of exposures to ubiquitous anthropogenic combustion emissions and friction-derived nanoparticles, industrial nanoplastics, the growing risk of wildfires, and the smoke plumes of soot. Ample consideration of pediatric and early adulthood hallmarks of Alzheimer's disease, Parkinson's disease, frontotemporal lobar degeneration, and amyotrophic lateral sclerosis and associations with neuropsychiatric and neurodevelopmental disorders in the process of setting, reviewing, and implementing standards for particulate matter (PM)2.5, ultrafine PM, and industrial nanoparticles must be of interest to US citizens.}, } @article {pmid38517530, year = {2024}, author = {Kotsia, E and Chroni, E and Alexandropoulou, A and Mills, C and Veltsista, D and Kefalopoulou, ZM and Michou, E}, title = {Dysphagia Assessments as Criteria in the 'Decision-Making Process' for Percutaneous Endoscopic Gastrostomy Placement in People with Amyotrophic Lateral Sclerosis: A Systematic Review.}, journal = {Dysphagia}, volume = {39}, number = {6}, pages = {977-988}, pmid = {38517530}, issn = {1432-0460}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/complications ; *Deglutition Disorders/etiology ; *Gastrostomy/methods ; *Clinical Decision-Making/methods ; Male ; Female ; }, abstract = {To review the assessment methods of dysphagia as a criterion for the decision-making process for Percutaneous Endoscopic Gastrostomy (PEG) placement in patients with Amyotrophic Lateral Sclerosis (ALS). Systematic review. A search was conducted in three databases (EMBASE, CINAHL, PUBMED) in December 2022 and updated in July 2023. Two reviewers independently screened, selected, and extracted data. Study quality was appraised using the Joanna Briggs Institute Critical Appraisal Tools. Systematic review registration number in the International Prospective Register of Systematic Reviews (PROSPERO): CRD42022385461. The searches identified 240 records. The 10 eligible studies included 2 case reports, 4 retrospective studies, 3 prospective studies, and 1 cohort observational study. Study quality was low, with most studies having moderate to high risk of bias. Dysphagia is a common criterion for decision-making. Dysphagia assessment is usually in the form of either self-reports, objective instrumental assessments, or both. Dysphagia is a common criterion for the decision-making process, yet is missing in clinical guidelines. Establishing the optimal means of dysphagia assessment is important for timely decision-making procedures, so that life-threatening consequences of dysphagia are minimized.}, } @article {pmid38517332, year = {2024}, author = {Brenner, D and Sieverding, K and Srinidhi, J and Zellner, S and Secker, C and Yilmaz, R and Dyckow, J and Amr, S and Ponomarenko, A and Tunaboylu, E and Douahem, Y and Schlag, JS and Rodríguez Martínez, L and Kislinger, G and Niemann, C and Nalbach, K and Ruf, WP and Uhl, J and Hollenbeck, J and Schirmer, L and Catanese, A and Lobsiger, CS and Danzer, KM and Yilmazer-Hanke, D and Münch, C and Koch, P and Freischmidt, A and Fetting, M and Behrends, C and Parlato, R and Weishaupt, JH}, title = {A TBK1 variant causes autophagolysosomal and motoneuron pathology without neuroinflammation in mice.}, journal = {The Journal of experimental medicine}, volume = {221}, number = {5}, pages = {}, pmid = {38517332}, issn = {1540-9538}, support = {//Medical Faculty Mannheim of Heidelberg University/ ; //University of Ulm/ ; 10.22.2.022MN//Fritz Thyssen Foundation/ ; 2022_EKES.18//Else Kröner-Fresenius-Stiftung/ ; //Frick Foundation for ALS Research/ ; WE 2791/7-1//Deutsche Forschungsgemeinschaft/ ; //Agence Nationale de la Recherche/ ; //Charité/ ; //Stifterverband für die Deutsche Wissenschaft/ ; }, mesh = {Animals ; Humans ; Mice ; *Amyotrophic Lateral Sclerosis/pathology ; *Frontotemporal Dementia/genetics/metabolism/pathology ; Motor Neurons/pathology ; Mutation ; Neuroinflammatory Diseases ; Phosphorylation ; Protein Serine-Threonine Kinases/genetics/metabolism ; }, abstract = {Heterozygous mutations in the TBK1 gene can cause amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The majority of TBK1-ALS/FTD patients carry deleterious loss-of-expression mutations, and it is still unclear which TBK1 function leads to neurodegeneration. We investigated the impact of the pathogenic TBK1 missense variant p.E696K, which does not abolish protein expression, but leads to a selective loss of TBK1 binding to the autophagy adaptor protein and TBK1 substrate optineurin. Using organelle-specific proteomics, we found that in a knock-in mouse model and human iPSC-derived motor neurons, the p.E696K mutation causes presymptomatic onset of autophagolysosomal dysfunction in neurons precipitating the accumulation of damaged lysosomes. This is followed by a progressive, age-dependent motor neuron disease. Contrary to the phenotype of mice with full Tbk1 knock-out, RIPK/TNF-α-dependent hepatic, neuronal necroptosis, and overt autoinflammation were not detected. Our in vivo results indicate autophagolysosomal dysfunction as a trigger for neurodegeneration and a promising therapeutic target in TBK1-ALS/FTD.}, } @article {pmid38516846, year = {2024}, author = {Kanazawa, T and Sato, W and Raveney, BJE and Takewaki, D and Kimura, A and Yamaguchi, H and Yokoi, Y and Saika, R and Takahashi, Y and Fujita, T and Saiki, S and Tamaoka, A and Oki, S and Yamamura, T}, title = {Pathogenic Potential of Eomesodermin-Expressing T-Helper Cells in Neurodegenerative Diseases.}, journal = {Annals of neurology}, volume = {95}, number = {6}, pages = {1093-1098}, doi = {10.1002/ana.26920}, pmid = {38516846}, issn = {1531-8249}, support = {16ek0109097h0002//Japan Multiple Sclerosis Society/ ; 17ek0109097h0003//Kato Memorial Trust for Nambyo Research/ ; 16ek0109155h0002//Mitsubishi Foundation/ ; 17ek0109155h0003//Practical Research Project for Rare/intractable Diseases from Japan Agency for Medical Research and Development, AMED/ ; 20FC0201//JSPS KAKENHI/ ; 30-5//National Institute of Neuroscience Intramural Research/ ; }, mesh = {Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; Alzheimer Disease/immunology/pathology/metabolism ; Amyotrophic Lateral Sclerosis/immunology ; Granzymes/metabolism ; *Neurodegenerative Diseases/immunology ; *T-Box Domain Proteins/metabolism ; *T-Lymphocytes, Helper-Inducer/immunology ; }, abstract = {Eomesodermin-expressing (Eomes[+]) T-helper (Th) cells show cytotoxic characteristics in secondary progressive multiple sclerosis. We found that Eomes[+] Th cell frequency was increased in the peripheral blood of amyotrophic lateral sclerosis and Alzheimer's disease patients. Furthermore, granzyme B production by Th cells from such patients was high compared with controls. A high frequency of Eomes[+] Th cells was observed in the initial (acutely progressive) stage of amyotrophic lateral sclerosis, and a positive correlation between Eomes[+] Th cell frequency and cognitive decline was observed in Alzheimer's disease patients. Therefore, Eomes[+] Th cells may be involved in the pathology of amyotrophic lateral sclerosis and Alzheimer's disease. ANN NEUROL 2024;95:1093-1098.}, } @article {pmid38516735, year = {2024}, author = {Li, X and Bedlack, R}, title = {Evaluating emerging drugs in phase II & III for the treatment of amyotrophic lateral sclerosis.}, journal = {Expert opinion on emerging drugs}, volume = {29}, number = {2}, pages = {93-102}, doi = {10.1080/14728214.2024.2333420}, pmid = {38516735}, issn = {1744-7623}, mesh = {*Amyotrophic Lateral Sclerosis/drug therapy/physiopathology ; Humans ; *Drug Development ; *Drugs, Investigational/pharmacology ; Animals ; *Clinical Trials, Phase II as Topic ; Clinical Trials, Phase III as Topic ; Drug Design ; Molecular Targeted Therapy ; Research Design ; }, abstract = {INTRODUCTION: Amyotrophic Lateral Sclerosis is a rapidly progressive motor neuron disorder causing severe disability and premature death. Owing to the advances in uncovering ALS pathophysiology, efficient clinical trial design and research advocacy program, several disease-modifying drugs have been approved for treating ALS. Despite this progress, ALS remains a rapidly disabling and life shortening condition. There is a critical need for more effective therapies.

AREAS COVERED: Here, we reviewed the emerging ALS therapeutics undergoing phase II & III clinical trials. To identify the investigational drugs, we searched ALS and phase II/III trials that are active and recruiting or not yet recruiting on clinicaltrials.gov and Pharmaprojects database.

EXPERT OPINION: The current pipeline is larger and more diverse than ever, with drugs targeting potential genetic and retroviral causes of ALS and drugs targeting a wide array of downstream pathways, including RNA metabolism, protein aggregation, integrated stress response and neuroinflammation.We remain most excited about those that target direct causes of ALS, e.g. antisense oligonucleotides targeting causative genes. Drugs that eliminate abnormal protein aggregates are also up-and-coming. Eventually, because of the heterogeneity of ALS pathophysiology, biomarkers that determine which biological events are most important for an individual ALS patient are needed.}, } @article {pmid38516553, year = {2023}, author = {Aishwarya, R and Abdullah, CS and Remex, NS and Nitu, S and Hartman, B and King, J and Bhuiyan, MAN and Rom, O and Miriyala, S and Panchatcharam, M and Orr, AW and Kevil, CG and Bhuiyan, MS}, title = {Pathological Sequelae Associated with Skeletal Muscle Atrophy and Histopathology in G93A*SOD1 Mice.}, journal = {Muscles (Basel, Switzerland)}, volume = {2}, number = {1}, pages = {51-74}, pmid = {38516553}, issn = {2813-0413}, support = {R00 HL150233/HL/NHLBI NIH HHS/United States ; K99 HL150233/HL/NHLBI NIH HHS/United States ; R01 DK134011/DK/NIDDK NIH HHS/United States ; R21 AA026708/AA/NIAAA NIH HHS/United States ; R01 HL152723/HL/NHLBI NIH HHS/United States ; P20 GM121307/GM/NIGMS NIH HHS/United States ; R01 HL098435/HL/NHLBI NIH HHS/United States ; R01 HL133497/HL/NHLBI NIH HHS/United States ; R01 HL149264/HL/NHLBI NIH HHS/United States ; R15 HL141998/HL/NHLBI NIH HHS/United States ; R01 HL145753/HL/NHLBI NIH HHS/United States ; R01 HL141155/HL/NHLBI NIH HHS/United States ; R21 AA025744/AA/NIAAA NIH HHS/United States ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a complex systemic disease that primarily involves motor neuron dysfunction and skeletal muscle atrophy. One commonly used mouse model to study ALS was generated by transgenic expression of a mutant form of human superoxide dismutase 1 (SOD1) gene harboring a single amino acid substitution of glycine to alanine at codon 93 (G93A*SOD1). Although mutant-SOD1 is ubiquitously expressed in G93A*SOD1 mice, a detailed analysis of the skeletal muscle expression pattern of the mutant protein and the resultant muscle pathology were never performed. Using different skeletal muscles isolated from G93A*SOD1 mice, we extensively characterized the pathological sequelae of histological, molecular, ultrastructural, and biochemical alterations. Muscle atrophy in G93A*SOD1 mice was associated with increased and differential expression of mutant-SOD1 across myofibers and increased MuRF1 protein level. In addition, high collagen deposition and myopathic changes sections accompanied the reduced muscle strength in the G93A*SOD1 mice. Furthermore, all the muscles in G93A*SOD1 mice showed altered protein levels associated with different signaling pathways, including inflammation, mitochondrial membrane transport, mitochondrial lipid uptake, and antioxidant enzymes. In addition, the mutant-SOD1 protein was found in the mitochondrial fraction in the muscles from G93A*SOD1 mice, which was accompanied by vacuolized and abnormal mitochondria, altered OXPHOS and PDH complex protein levels, and defects in mitochondrial respiration. Overall, we reported the pathological sequelae observed in the skeletal muscles of G93A*SOD1 mice resulting from the whole-body mutant-SOD1 protein expression.}, } @article {pmid38516187, year = {2024}, author = {Dudas, EF and Tully, MD and Foldes, T and Kelly, G and Tartaglia, GG and Pastore, A}, title = {The structural properties of full-length annexin A11.}, journal = {Frontiers in molecular biosciences}, volume = {11}, number = {}, pages = {1347741}, pmid = {38516187}, issn = {2296-889X}, abstract = {Annexin A11 (ANXA11) is a calcium-dependent phospholipid-binding protein belonging to the annexin protein family and implicated in the neurodegenerative amyotrophic lateral sclerosis. Structurally, ANXA11 contains a conserved calcium-binding C-terminal domain common to all annexins and a putative intrinsically unfolded N-terminus specific for ANXA11. Little is known about the structure and functions of this region of the protein. By analogy with annexin A1, it was suggested that residues 38 to 59 within the ANXA11 N-terminus could form a helical region that would be involved in interactions. Interestingly, this region contains residues that, when mutated, may lead to clinical manifestations. In the present study, we have studied the structural features of the full-length protein with special attention to the N-terminal region using a combination of biophysical techniques which include nuclear magnetic resonance and small angle X-ray scattering. We show that the N-terminus is intrinsically disordered and that the overall features of the protein are not markedly affected by the presence of calcium. We also analyzed the 38-59 helix hypothesis using synthetic peptides spanning both the wild-type sequence and clinically relevant mutations. We show that the peptides have a remarkable character typical of a native helix and that mutations do not alter the behaviour suggesting that they are required for interactions rather than being structurally important. Our work paves the way to a more thorough understanding of the ANXA11 functions.}, } @article {pmid38515787, year = {2024}, author = {Wang, L and Fang, X and Ling, B and Wang, F and Xia, Y and Zhang, W and Zhong, T and Wang, X}, title = {Research progress on ferroptosis in the pathogenesis and treatment of neurodegenerative diseases.}, journal = {Frontiers in cellular neuroscience}, volume = {18}, number = {}, pages = {1359453}, pmid = {38515787}, issn = {1662-5102}, abstract = {Globally, millions of individuals are impacted by neurodegenerative disorders including Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), and Alzheimer's disease (AD). Although a great deal of energy and financial resources have been invested in disease-related research, breakthroughs in therapeutic approaches remain elusive. The breakdown of cells usually happens together with the onset of neurodegenerative diseases. However, the mechanism that triggers neuronal loss is unknown. Lipid peroxidation, which is iron-dependent, causes a specific type of cell death called ferroptosis, and there is evidence its involvement in the pathogenic cascade of neurodegenerative diseases. However, the specific mechanisms are still not well known. The present article highlights the basic processes that underlie ferroptosis and the corresponding signaling networks. Furthermore, it provides an overview and discussion of current research on the role of ferroptosis across a variety of neurodegenerative conditions.}, } @article {pmid38515451, year = {2024}, author = {Zoccolella, S and Milella, G and Giugno, A and Devitofrancesco, V and Damato, R and Tamburrino, L and Misceo, S and Filardi, M and Logroscino, G}, title = {Neurophysiological indices for split phenomena: correlation with age and sex and potential implications in amyotrophic lateral sclerosis.}, journal = {Frontiers in neurology}, volume = {15}, number = {}, pages = {1371953}, pmid = {38515451}, issn = {1664-2295}, abstract = {BACKGROUND: Split phenomena (SP) are characterized by patterns of differential muscle wasting and atrophy, which are highly prevalent in amyotrophic lateral sclerosis (ALS) patients. Several neurophysiological indicators, including the split-hand index (SHI), split-leg index (SLI), and split-elbow index (SEI), have been proposed to assess SP. Nevertheless, their cutoff values and the impact of age and sex on these measures remain unclear.

METHODS: We prospectively collected neurophysiological data from 300 healthy adult subjects. The following indices were measured from compound muscle action potentials (CMAPs): SHI [abductor pollicis brevis (APBcmap) x first dorsal interosseous (FDI)cmap/adductor digiti minimi (ADMcmap)], SEI (BICEPScmap/TRICEPScmap), SLI (extensor digit brevis (EDB)cmap/abductor Hallucis (AH)cmap), and the neurophysiological ratios APBcmap /ADMcmap and FDIcmap/ADMcmap. Multiple linear regression analysis was used to investigate the association between age, sex, CMAPs, and neurophysiological indicators.

RESULTS: The median SHI was 10.4, with a median APBcmap/ADMcmap ratio of 0.9 and a median FDIcmap/ADMcmap ratio of 1.2. The median SEI was 1.6 (IQR:1.1-2.4) and the median SLI was 0.7 (IQR:0.5-1.0). Negative associations were observed between age, most of the CMAPs, and all the neurophysiological indices, except for SLI. The male subjects exhibited significantly higher CMAP values for the first dorsal interosseous (FDI), biceps, and SHI compared to the female participants.

CONCLUSION: Our findings highlight the importance of age- and sex-adjusted normative data for SP indices, which could enhance their diagnostic accuracy and clinical utility in patients with ALS. The SL index appears to be the most reliable indicator, as it showed no significant association with age or sex.}, } @article {pmid38515326, year = {2024}, author = {Lee, DY and Kwon, YN and Lee, K and Kim, SJ and Sung, JJ}, title = {Dual effects of TGF-β inhibitor in ALS - inhibit contracture and neurodegeneration.}, journal = {Journal of neurochemistry}, volume = {168}, number = {9}, pages = {2495-2514}, doi = {10.1111/jnc.16102}, pmid = {38515326}, issn = {1471-4159}, support = {2018R1A5A2025964//National Research Foundation of Korea (NRF) Grant/ ; 2019M3C7A1031867//National Research Foundation of Korea (NRF) Grant/ ; }, mesh = {Animals ; *Amyotrophic Lateral Sclerosis/drug therapy/pathology/metabolism ; Mice ; *Transforming Growth Factor beta/metabolism/antagonists & inhibitors ; *Contracture/drug therapy/prevention & control ; Mice, Transgenic ; Male ; Mice, Inbred C57BL ; Piperidines/pharmacology/therapeutic use ; Humans ; }, abstract = {As persistent elevation of transforming growth factor-β (TGF-β) promotes fibrosis of muscles and joints and accelerates disease progression in amyotrophic lateral sclerosis (ALS), we investigated whether inhibition of TGF-β would be effective against both exacerbations. The effects of TGF-β and its inhibitor on myoblasts and fibroblasts were tested in vitro and confirmed in vivo, and the dual action of a TGF-β inhibitor in ameliorating the pathogenic role of TGF-β in ALS mice was identified. In the peripheral neuromuscular system, fibrosis in the muscles and joint cavities induced by excessive TGF-β causes joint contracture and muscular degeneration, which leads to motor dysfunction. In an ALS mouse model, an increase in TGF-β in the central nervous system (CNS), consistent with astrocyte activity, was associated with M1 microglial activity and pro-inflammatory conditions, as well as with neuronal cell death. Treatment with the TGF-β inhibitor halofuginone could prevent musculoskeletal fibrosis, resulting in the alleviation of joint contracture and delay of motor deterioration in ALS mice. Halofuginone could also reduce glial cell-induced neuroinflammation and neuronal apoptosis. These dual therapeutic effects on both the neuromuscular system and the CNS were observed from the beginning to the end stages of ALS; as a result, treatment with a TGF-β inhibitor from the early stage of disease delayed the time of symptom exacerbation in ALS mice, which led to prolonged survival.}, } @article {pmid38514815, year = {2024}, author = {Baxter, RC}, title = {Endocrine and cellular physiology and pathology of the insulin-like growth factor acid-labile subunit.}, journal = {Nature reviews. Endocrinology}, volume = {20}, number = {7}, pages = {414-425}, pmid = {38514815}, issn = {1759-5037}, mesh = {Humans ; Animals ; *Glycoproteins/metabolism ; Carrier Proteins/metabolism ; Insulin-Like Growth Factor I/metabolism ; Mice ; Insulin-Like Growth Factor Binding Proteins/metabolism/physiology ; Insulin-Like Growth Factor II/metabolism ; Endocrine System/metabolism ; Insulin-Like Peptides ; }, abstract = {The acid-labile subunit (ALS) of the insulin-like growth factor (IGF) binding protein (IGFBP) complex, encoded in humans by IGFALS, has a vital role in regulating the endocrine transport and bioavailability of IGF-1 and IGF-2. Accordingly, ALS has a considerable influence on postnatal growth and metabolism. ALS is a leucine-rich glycoprotein that forms high-affinity ternary complexes with IGFBP-3 or IGFBP-5 when they are occupied by either IGF-1 or IGF-2. These complexes constitute a stable reservoir of circulating IGFs, blocking the potentially hypoglycaemic activity of unbound IGFs. ALS is primarily synthesized by hepatocytes and its expression is lower in non-hepatic tissues. ALS synthesis is strongly induced by growth hormone and suppressed by IL-1β, thus potentially serving as a marker of growth hormone secretion and/or activity and of inflammation. IGFALS mutations in humans and Igfals deletion in mice cause modest growth retardation and pubertal delay, accompanied by decreased osteogenesis and enhanced adipogenesis. In hepatocellular carcinoma, IGFALS is described as a tumour suppressor; however, its contribution to other cancers is not well delineated. This Review addresses the endocrine physiology and pathology of ALS, discusses the latest cell and proteomic studies that suggest emerging cellular roles for ALS and outlines its involvement in other disease states.}, } @article {pmid38514515, year = {2024}, author = {Finsterer, J}, title = {Amyotrophic Lateral Sclerosis due to ALS2 Pathogenic Variant Masquerading as Cerebral Palsy: Correspondence.}, journal = {Indian journal of pediatrics}, volume = {91}, number = {9}, pages = {988}, pmid = {38514515}, issn = {0973-7693}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/genetics ; *Cerebral Palsy/diagnosis ; Diagnosis, Differential ; Guanine Nucleotide Exchange Factors/genetics ; Female ; Child, Preschool ; }, } @article {pmid38512820, year = {2024}, author = {Bartolomé-Nafría, A and García-Pardo, J and Ventura, S}, title = {Mutations in human prion-like domains: pathogenic but not always amyloidogenic.}, journal = {Prion}, volume = {18}, number = {1}, pages = {28-39}, pmid = {38512820}, issn = {1933-690X}, mesh = {Humans ; *Prions/metabolism ; *Heterogeneous-Nuclear Ribonucleoprotein Group A-B/genetics/metabolism ; *Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology ; *Frontotemporal Dementia/genetics/metabolism/pathology ; Mutation ; }, abstract = {Heterogeneous nuclear ribonucleoproteins (hnRNPs) are multifunctional proteins with integral roles in RNA metabolism and the regulation of alternative splicing. These proteins typically contain prion-like domains of low complexity (PrLDs or LCDs) that govern their assembly into either functional or pathological amyloid fibrils. To date, over 60 mutations targeting the LCDs of hnRNPs have been identified and associated with a spectrum of neurodegenerative diseases including amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and Alzheimer's disease (AD). The cryo-EM structures of pathological and functional fibrils formed by different hnRNPs have been recently elucidated, including those of hnRNPA1, hnRNPA2, hnRNPDL-2, TDP-43, and FUS. In this review, we discuss the structural features of these amyloid assemblies, placing particular emphasis on scrutinizing the impact of prevalent disease-associated mutations mapping within their LCDs. By performing systematic energy calculations, we reveal a prevailing trend of destabilizing effects induced by these mutations in the amyloid structure, challenging the traditionally assumed correlation between pathogenicity and amyloidogenic propensity. Understanding the molecular basis of this discrepancy might provide insights for developing targeted therapeutic strategies to combat hnRNP-associated diseases.}, } @article {pmid38512130, year = {2024}, author = {Pak, V and Adewale, Q and Bzdok, D and Dadar, M and Zeighami, Y and Iturria-Medina, Y}, title = {Distinctive whole-brain cell types predict tissue damage patterns in thirteen neurodegenerative conditions.}, journal = {eLife}, volume = {12}, number = {}, pages = {}, pmid = {38512130}, issn = {2050-084X}, support = {CIHR Project Grant 2020/CAPMC/CIHR/Canada ; }, mesh = {Humans ; Brain ; *Neurodegenerative Diseases ; Neurons ; *Parkinson Disease ; Brain Mapping ; }, abstract = {For over a century, brain research narrative has mainly centered on neuron cells. Accordingly, most neurodegenerative studies focus on neuronal dysfunction and their selective vulnerability, while we lack comprehensive analyses of other major cell types' contribution. By unifying spatial gene expression, structural MRI, and cell deconvolution, here we describe how the human brain distribution of canonical cell types extensively predicts tissue damage in 13 neurodegenerative conditions, including early- and late-onset Alzheimer's disease, Parkinson's disease, dementia with Lewy bodies, amyotrophic lateral sclerosis, mutations in presenilin-1, and 3 clinical variants of frontotemporal lobar degeneration (behavioral variant, semantic and non-fluent primary progressive aphasia) along with associated three-repeat and four-repeat tauopathies and TDP43 proteinopathies types A and C. We reconstructed comprehensive whole-brain reference maps of cellular abundance for six major cell types and identified characteristic axes of spatial overlapping with atrophy. Our results support the strong mediating role of non-neuronal cells, primarily microglia and astrocytes, in spatial vulnerability to tissue loss in neurodegeneration, with distinct and shared across-disorder pathomechanisms. These observations provide critical insights into the multicellular pathophysiology underlying spatiotemporal advance in neurodegeneration. Notably, they also emphasize the need to exceed the current neuro-centric view of brain diseases, supporting the imperative for cell-specific therapeutic targets in neurodegeneration.}, } @article {pmid38511674, year = {2024}, author = {Amesaka, H and Hara, M and Sakai, Y and Shintani, A and Sue, K and Yamanaka, T and Tanaka, SI and Furukawa, Y}, title = {Engineering a monobody specific to monomeric Cu/Zn-superoxide dismutase associated with amyotrophic lateral sclerosis.}, journal = {Protein science : a publication of the Protein Society}, volume = {33}, number = {4}, pages = {e4961}, pmid = {38511674}, issn = {1469-896X}, support = {19H05765//Grants-in-Aid for Scientific Research on Innovative Areas/ ; 20H05516//Grants-in-Aid for Scientific Research on Innovative Areas/ ; 22H02768//Scientific Research (B)/ ; 21K05386//Scientific Research (C)/ ; 22K19389//Ministry of Education, Culture, Sports, Science and Technology of Japan/ ; }, mesh = {Humans ; Superoxide Dismutase-1/chemistry ; *Amyotrophic Lateral Sclerosis/genetics ; Protein Folding ; Superoxide Dismutase/chemistry ; Saccharomyces cerevisiae/metabolism ; Zinc/metabolism ; Mutation ; }, abstract = {Misfolding of mutant Cu/Zn-superoxide dismutase (SOD1) has been implicated in familial form of amyotrophic lateral sclerosis (ALS). A natively folded SOD1 forms a tight homodimer, and the dimer dissociation has been proposed to trigger the oligomerization/aggregation of SOD1. Besides increasing demand for probes allowing the detection of monomerized forms of SOD1 in various applications, the development of probes has been limited to conventional antibodies. Here, we have developed Mb(S4) monobody, a small synthetic binding protein based on the fibronectin type III scaffold, that recognizes a monomeric but not dimeric form of SOD1 by performing combinatorial library selections using phage and yeast-surface display methods. Although Mb(S4) was characterized by its excellent selectivity to the monomeric conformation of SOD1, the monomeric SOD1/Mb(S4) complex was not so stable (apparent Kd ~ μM) as to be detected in conventional pull-down experiments. Instead, the complex of Mb(S4) with monomeric but not dimeric SOD1 was successfully trapped by proximity-enabled chemical crosslinking even when reacted in the cell lysates. We thus anticipate that Mb(S4) binding followed by chemical crosslinking would be a useful strategy for in vitro and also ex vivo detection of the monomeric SOD1 proteins.}, } @article {pmid38511649, year = {2024}, author = {Craig, RA and De Vicente, J and Estrada, AA and Feng, JA and Lexa, KW and Canet, MJ and Dowdle, WE and Erickson, RI and Flores, BN and Haddick, PCG and Kane, LA and Lewcock, JW and Moerke, NJ and Poda, SB and Sweeney, Z and Takahashi, RH and Tong, V and Wang, J and Yulyaningsih, E and Solanoy, H and Scearce-Levie, K and Sanchez, PE and Tang, L and Xu, M and Zhang, R and Osipov, M}, title = {Discovery of DNL343: A Potent, Selective, and Brain-Penetrant eIF2B Activator Designed for the Treatment of Neurodegenerative Diseases.}, journal = {Journal of medicinal chemistry}, volume = {67}, number = {7}, pages = {5758-5782}, doi = {10.1021/acs.jmedchem.3c02422}, pmid = {38511649}, issn = {1520-4804}, mesh = {Humans ; *Neurodegenerative Diseases/drug therapy/metabolism ; *Amyotrophic Lateral Sclerosis/drug therapy/metabolism ; Mutation ; Eukaryotic Initiation Factor-2B/genetics/metabolism ; Brain/metabolism ; *Leukoencephalopathies/metabolism ; }, abstract = {Eukaryotic translation initiation factor 2B (eIF2B) is a key component of the integrated stress response (ISR), which regulates protein synthesis and stress granule formation in response to cellular insult. Modulation of the ISR has been proposed as a therapeutic strategy for treatment of neurodegenerative diseases such as vanishing white matter (VWM) disease and amyotrophic lateral sclerosis (ALS) based on its ability to improve cellular homeostasis and prevent neuronal degeneration. Herein, we report the small-molecule discovery campaign that identified potent, selective, and CNS-penetrant eIF2B activators using both structure- and ligand-based drug design. These discovery efforts culminated in the identification of DNL343, which demonstrated a desirable preclinical drug profile, including a long half-life and high oral bioavailability across preclinical species. DNL343 was progressed into clinical studies and is currently undergoing evaluation in late-stage clinical trials for ALS.}, } @article {pmid38511172, year = {2024}, author = {Rossi, JJ}, title = {Accessory oligos for neuronal delivery of therapeutic siRNAs for ALS.}, journal = {Molecular therapy. Nucleic acids}, volume = {35}, number = {2}, pages = {102153}, pmid = {38511172}, issn = {2162-2531}, } @article {pmid38511059, year = {2024}, author = {Casado Gama, H and Amorós, MA and Andrade de Araújo, M and Sha, CM and Vieira, MPS and Torres, RGD and Souza, GF and Junkes, JA and Dokholyan, NV and Leite Góes Gitaí, D and Duzzioni, M}, title = {Systematic review and meta-analysis of dysregulated microRNAs derived from liquid biopsies as biomarkers for amyotrophic lateral sclerosis.}, journal = {Non-coding RNA research}, volume = {9}, number = {2}, pages = {523-535}, pmid = {38511059}, issn = {2468-0540}, abstract = {The discovery of disease-specific biomarkers, such as microRNAs (miRNAs), holds the potential to transform the landscape of Amyotrophic Lateral Sclerosis (ALS) by facilitating timely diagnosis, monitoring treatment response, and accelerating drug discovery. Such advancement could ultimately improve the quality of life and survival rates for ALS patients. Despite more than a decade of research, no miRNA biomarker candidate has been translated into clinical practice. We conducted a systematic review and meta-analysis to quantitatively synthesize data from original studies that analyzed miRNA expression from liquid biopsies via PCR and compared them to healthy controls. Our analysis encompasses 807 miRNA observations from 31 studies, stratified according to their source tissue. We identified consistently dysregulated miRNAs in serum (hsa-miR-3665, -4530, -4745-5p, -206); blood (hsa-miR-338-3p, -183-5p); cerebrospinal fluid (hsa-miR-34a-3p); plasma (hsa-miR-206); and neural-enriched extracellular vesicles from plasma (hsa-miR-146a-5p, -151a-5p, -10b-5p, -29b-3p, and -4454). The meta-analyses provided further support for the upregulation of hsa-miR-206, hsa-miR-338-3p, hsa-miR-146a-5p and hsa-miR-151a-5p, and downregulation of hsa-miR-183-5p, hsa-miR-10b-5p, hsa-miR-29b-3p, and hsa-miR-4454 as consistent indicators of ALS across independent studies. Our findings provide valuable insights into the current understanding of miRNAs' dysregulated expression in ALS patients and on the researchers' choices of methodology. This work contributes to the ongoing efforts towards discovering disease-specific biomarkers.}, } @article {pmid38510000, year = {2024}, author = {Ditan, ID and Turalde, CWR}, title = {Treatment gaps in the care of amyotrophic lateral sclerosis in the Philippines: A scoping review.}, journal = {Heliyon}, volume = {10}, number = {6}, pages = {e27944}, pmid = {38510000}, issn = {2405-8440}, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive disease affecting both the upper and lower motor neurons. Much of the management of ALS is supportive with the goal of maximizing patient quality of life. While the Philippines was participative in the "Ice Bucket Challenge" in 2014, it is up for investigation whether substantial changes occurred to improve healthcare for ALS patients. This study aims to evaluate the treatment gaps in the management of ALS in the Philippines through a scoping review. Data on epidemiology, health systems, and pharmacotherapy available regarding ALS in the local setting were synthesized. Nine articles were included. As of July 2023, there were only four indexed studies on ALS from the Philippines. Five of the included articles investigated ALS in Filipino populations but were not authored by Filipinos nor affiliated with Philippine institutions. The available literature showed a distinct lack of local ALS epidemiologic data, as well as limited availability in diagnostic centers, medications, health financing options, and digestible information for Filipinos. The limitations in managing ALS in the country are multifactorial - from political, medical, and social. It is imperative to establish a national database, financing systems, support groups, and accessible diagnostic centers for ALS patients.}, } @article {pmid38509062, year = {2024}, author = {Funes, S and Jung, J and Gadd, DH and Mosqueda, M and Zhong, J and Shankaracharya, and Unger, M and Stallworth, K and Cameron, D and Rotunno, MS and Dawes, P and Fowler-Magaw, M and Keagle, PJ and McDonough, JA and Boopathy, S and Sena-Esteves, M and Nickerson, JA and Lutz, C and Skarnes, WC and Lim, ET and Schafer, DP and Massi, F and Landers, JE and Bosco, DA}, title = {Expression of ALS-PFN1 impairs vesicular degradation in iPSC-derived microglia.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {2497}, pmid = {38509062}, issn = {2041-1723}, support = {RF1 AG068281/AG/NIA NIH HHS/United States ; R21 NS120126/NS/NINDS NIH HHS/United States ; R01 GM147677/GM/NIGMS NIH HHS/United States ; R01 NS108769/NS/NINDS NIH HHS/United States ; R01 MH113743/MH/NIMH NIH HHS/United States ; R01 NS117533/NS/NINDS NIH HHS/United States ; R01 GM137529/GM/NIGMS NIH HHS/United States ; U54 OD020351/OD/NIH HHS/United States ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism ; Microglia/metabolism ; *Induced Pluripotent Stem Cells/metabolism ; Profilins/metabolism ; *Neurodegenerative Diseases ; Mutation ; }, abstract = {Microglia play a pivotal role in neurodegenerative disease pathogenesis, but the mechanisms underlying microglia dysfunction and toxicity remain to be elucidated. To investigate the effect of neurodegenerative disease-linked genes on the intrinsic properties of microglia, we studied microglia-like cells derived from human induced pluripotent stem cells (iPSCs), termed iMGs, harboring mutations in profilin-1 (PFN1) that are causative for amyotrophic lateral sclerosis (ALS). ALS-PFN1 iMGs exhibited evidence of lipid dysmetabolism, autophagy dysregulation and deficient phagocytosis, a canonical microglia function. Mutant PFN1 also displayed enhanced binding affinity for PI3P, a critical signaling molecule involved in autophagic and endocytic processing. Our cumulative data implicate a gain-of-toxic function for mutant PFN1 within the autophagic and endo-lysosomal pathways, as administration of rapamycin rescued phagocytic dysfunction in ALS-PFN1 iMGs. These outcomes demonstrate the utility of iMGs for neurodegenerative disease research and implicate microglial vesicular degradation pathways in the pathogenesis of these disorders.}, } @article {pmid38508480, year = {2024}, author = {Bager, P and Hvas, CL and Dahlerup, JF}, title = {Severe Fatigue in Inflammatory Bowel Disease: Dopaminergic Therapy With Modafinil or Vitamin Therapy With Thiamine.}, journal = {Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association}, volume = {22}, number = {11}, pages = {2348-2349}, doi = {10.1016/j.cgh.2024.03.002}, pmid = {38508480}, issn = {1542-7714}, mesh = {Humans ; *Modafinil/therapeutic use ; *Fatigue/drug therapy ; *Inflammatory Bowel Diseases/drug therapy/complications ; *Thiamine/therapeutic use ; Treatment Outcome ; Male ; Female ; Middle Aged ; }, abstract = {We found Moulton et al's[1] illustrative case series of 10 patients with inflammatory bowel disease (IBD) and chronic fatigue, all presenting with depression, particularly interesting. [1] Among the patients, 8 previously had undergone treatment with multiple psychotropic medications, and 2 had active IBD as indicated by increased fecal calprotectin levels. Remarkably, all 10 patients responded positively to open-label treatment with modafinil, a central nervous system stimulant that blocks dopamine reuptake transport, which resulted in an impressive improvement in their fatigue symptoms. At baseline, the self-reported mean fatigue score was 16, measured on the IBD Fatigue Assessment Scale (IBD-FAS), which ranges up to 20, and with levels higher than 11 indicating severe fatigue. After 6 months of modafinil treatment, the mean fatigue score was 6.7.[1].}, } @article {pmid38506473, year = {2024}, author = {Lillo, P and Zitko, P and Godoy-Reyes, G and Asenjo, G and Sáez, D and Cea, G and Navarrete, P and Valenzuela, D and Hughes, R and Heverin, M and Logroscino, G and Hardiman, O}, title = {Incidence of amyotrophic lateral sclerosis in Chile.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {25}, number = {5-6}, pages = {528-532}, doi = {10.1080/21678421.2024.2329706}, pmid = {38506473}, issn = {2167-9223}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/epidemiology/diagnosis ; Male ; Female ; Chile/epidemiology ; Incidence ; Middle Aged ; Aged ; Adult ; Cohort Studies ; Aged, 80 and over ; Survival Rate/trends ; Registries ; }, abstract = {OBJECTIVE: This study aimed to estimate amyotrophic lateral sclerosis (ALS) incidence and survival rates in the Metropolitan region of Chile.

METHODS: We conducted a cohort study of ALS cases in the Metropolitan Region from 2016 to 2019. A total of 219 ALS patients were recruited from Corporación ELA-Chile registry, in collaboration with neurologists from Sociedad de Neurología, Psiquiatría y Neurocirugía de Chile. We calculated incidence rates by sex and age and determined median survival from onset and diagnosis. Survival analysis used the Kaplan-Meier statistic, estimating hazard ratios for age, sex, time from symptom onset and from diagnosis using a Weibull regression model. All analyses were done using R 4.1.0.

RESULTS: Overall, ALS diagnosis incidence was 0.97 cases per 100,000 inhabitants, peaking in the 70-79 age group and declining thereafter. The male-to-female ratio was 1.23. The median time to death from diagnosis was 2.3 years (95% confidence interval [CI]: 1.9-2.5), and from the first symptom, it was 3.1 years (95% CI: 2.8-3.5).

CONCLUSIONS: This is the first population-based study reporting ALS incidence and survival rates in Chile's Metropolitan region. Incidence resembled other Latin American studies. Median survival from diagnosis and from the first symptom were in line with previous findings. Our results corroborated lower ALS rates in Latin America, consistent with prior research.}, } @article {pmid38505945, year = {2024}, author = {Kutlubaev, MA and Areprintseva, DK and Radakovic, R and Pervushina, EV}, title = {Psychometric properties of the Russian version of the Edinburgh cognitive and behavioral amyotrophic lateral sclerosis screen.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {25}, number = {7-8}, pages = {785-787}, doi = {10.1080/21678421.2024.2328579}, pmid = {38505945}, issn = {2167-9223}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/psychology/diagnosis/complications ; Male ; Female ; Middle Aged ; *Psychometrics/methods ; Aged ; Russia/epidemiology ; Reproducibility of Results ; *Neuropsychological Tests/statistics & numerical data ; Adult ; Cognitive Dysfunction/diagnosis/etiology/psychology ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative condition with observable cognitive and behavioral impairment. The Edinburgh Cognitive and Behavioral ALS Screen (ECAS) is a tool developed specifically for people with ALS (pwALS) and previously translated into Russian, but the psychometric properties have not yet been explored. The aim was to explore and determine the psychometric properties of the Russian-version of ECAS (ECAS-R).

METHODS: 56 Russian speaking pwALS, 32 of their caregivers and 26 healthy controls were recruited for the study. They completed the ECAS-R, Patient Health Questionnaire-9 (PHQ-9) and Montreal Cognitive Assessment (MoCA). King Staging System was also utilized. Internal consistency, divergent and convergent validity, as well as culturally-derived cutoff scores of ECAS-R were determined.

RESULTS: The internal consistency of ECAS-R was good (Cronbach's alpha = 0.73). Convergent validity was observed though a strong correlation between the ECAS-R and MoCA scores. No correlation between ECAS-R and PHQ-9 were observed in terms of divergent validity. Based on culturally-derived cutoff scores, 64.2% (N = 36) of pwALS displayed cognitive impairment, with the most affected cognitive domains as executive function and language. Apathy was the most common behavioral impairment for pwALS followed by a loss of sympathy/empathy.

CONCLUSIONS: The ECAS-R is valid and reliable tool for the screening for the cognitive and behavioral impairment in Russian-speaking pwALS, with culturally-derived cutoffs presented.}, } @article {pmid38505770, year = {2024}, author = {Shi, J and Wang, Z and Yi, M and Xie, S and Zhang, X and Tao, D and Liu, Y and Yang, Y}, title = {Evidence based on Mendelian randomization and colocalization analysis strengthens causal relationships between structural changes in specific brain regions and risk of amyotrophic lateral sclerosis.}, journal = {Frontiers in neuroscience}, volume = {18}, number = {}, pages = {1333782}, pmid = {38505770}, issn = {1662-4548}, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the degeneration of motor neurons in the brain and spinal cord with a poor prognosis. Previous studies have observed cognitive decline and changes in brain morphometry in ALS patients. However, it remains unclear whether the brain structural alterations contribute to the risk of ALS. In this study, we conducted a bidirectional two-sample Mendelian randomization (MR) and colocalization analysis to investigate this causal relationship.

METHODS: Summary data of genome-wide association study were obtained for ALS and the brain structures, including surface area (SA), thickness and volume of subcortical structures. Inverse-variance weighted (IVW) method was used as the main estimate approach. Sensitivity analysis was conducted detect heterogeneity and pleiotropy. Colocalization analysis was performed to calculate the posterior probability of causal variation and identify the common genes.

RESULTS: In the forward MR analysis, we found positive associations between the SA in four cortical regions (lingual, parahippocampal, pericalcarine, and middle temporal) and the risk of ALS. Additionally, decreased thickness in nine cortical regions (caudal anterior cingulate, frontal pole, fusiform, inferior temporal, lateral occipital, lateral orbitofrontal, pars orbitalis, pars triangularis, and pericalcarine) was significantly associated with a higher risk of ALS. In the reverse MR analysis, genetically predicted ALS was associated with reduced thickness in the bankssts and increased thickness in the caudal middle frontal, inferior parietal, medial orbitofrontal, and superior temporal regions. Colocalization analysis revealed the presence of shared causal variants between the two traits.

CONCLUSION: Our results suggest that altered brain morphometry in individuals with high ALS risk may be genetically mediated. The causal associations of widespread multifocal extra-motor atrophy in frontal and temporal lobes with ALS risk support the notion of a continuum between ALS and frontotemporal dementia. These findings enhance our understanding of the cortical structural patterns in ALS and shed light on potentially viable therapeutic targets.}, } @article {pmid38505661, year = {2023}, author = {Alix, JJP and Plesia, M and Schooling, CN and Dudgeon, AP and Kendall, CA and Kadirkamanathan, V and McDermott, CJ and Gorman, GS and Taylor, RW and Mead, RJ and Shaw, PJ and Day, JC}, title = {Non-negative matrix factorisation of Raman spectra finds common patterns relating to neuromuscular disease across differing equipment configurations, preclinical models and human tissue.}, journal = {Journal of Raman spectroscopy : JRS}, volume = {54}, number = {3}, pages = {258-268}, pmid = {38505661}, issn = {0377-0486}, support = {/WT_/Wellcome Trust/United Kingdom ; MC_PC_15034/MRC_/Medical Research Council/United Kingdom ; }, abstract = {Raman spectroscopy shows promise as a biomarker for complex nerve and muscle (neuromuscular) diseases. To maximise its potential, several challenges remain. These include the sensitivity to different instrument configurations, translation across preclinical/human tissues and the development of multivariate analytics that can derive interpretable spectral outputs for disease identification. Nonnegative matrix factorisation (NMF) can extract features from high-dimensional data sets and the nonnegative constraint results in physically realistic outputs. In this study, we have undertaken NMF on Raman spectra of muscle obtained from different clinical and preclinical settings. First, we obtained and combined Raman spectra from human patients with mitochondrial disease and healthy volunteers, using both a commercial microscope and in-house fibre optic probe. NMF was applied across all data, and spectral patterns common to both equipment configurations were identified. Linear discriminant models utilising these patterns were able to accurately classify disease states (accuracy 70.2-84.5%). Next, we applied NMF to spectra obtained from the mdx mouse model of a Duchenne muscular dystrophy and patients with dystrophic muscle conditions. Spectral fingerprints common to mouse/human were obtained and able to accurately identify disease (accuracy 79.5-98.8%). We conclude that NMF can be used to analyse Raman data across different equipment configurations and the preclinical/clinical divide. Thus, the application of NMF decomposition methods could enhance the potential of Raman spectroscopy for the study of fatal neuromuscular diseases.}, } @article {pmid38505513, year = {2023}, author = {Kamp, N and Krenn, P and Avian, M and Sass, O}, title = {Comparability of multi-temporal DTMs derived from different LiDAR platforms: Error sources and uncertainties in the application of geomorphic impact studies.}, journal = {Earth surface processes and landforms}, volume = {48}, number = {6}, pages = {1152-1175}, pmid = {38505513}, issn = {1096-9837}, abstract = {Multi-temporal digital terrain models (DTMs) derived from airborne or uncrewed aerial vehicle (UAV)-borne light detection and ranging (LiDAR) platforms are frequently used tools in geomorphic impact studies. Accurate estimation of mobilized sediments from multi-temporal DTMs is indispensable for hazard assessment. To study volumetric changes in alpine environments it is crucial to identify and discuss different kind of error sources in multi-temporal data. We subdivided errors into those caused by data acquisition, data processing, and spatial properties of the terrain. In terms of the quantification of surface changes, the propagation of errors can lead to high uncertainties. Three alpine catchments with different LiDAR point clouds of different origins (airborne laser scanning [ALS], UAV-borne laser scanning [ULS]), varying point densities, accuracies and qualities were analysed, and used as basis for interpolating DTMs. The workflow was developed in the Schöttlbach area in Styria and later applied to further catchments in Austria. The main aim of the presented work is a comprehensive DTM uncertainty analysis specially designed for geomorphic impact studies, with a resulting uncertainty analysis serving as input for a change detection tool. Our findings reveal that geomorphic impact studies need the careful distinction between actual surface changes and different data uncertainties. ULS combines the benefits of terrestrial laser scanning with all the benefits of ALS. However, the use of ULS data does not necessarily improve the results of the analysis since the high level of detail is not always helpful in geomorphic impact studies. In order to make the different point clouds and DTMs comparable the quality of the ULS point cloud had to be reduced to fit the accuracy of the reference data (older ALS point clouds). Using a point cloud with a high point density with a regular planimetric point spacing and less data gaps, in the best case collected during leaf-off conditions (e.g., cross-flight strategy) turned out to be sufficient for our geomorphic research purposes.}, } @article {pmid38504981, year = {2024}, author = {Cao, W and Cao, Z and Tang, L and Xu, C and Fan, D}, title = {Immune-mediated diseases are associated with a higher risk of ALS incidence: a prospective cohort study from the UK Biobank.}, journal = {Frontiers in immunology}, volume = {15}, number = {}, pages = {1356132}, pmid = {38504981}, issn = {1664-3224}, mesh = {Male ; Female ; Humans ; Prospective Studies ; UK Biobank ; *Amyotrophic Lateral Sclerosis/epidemiology ; Biological Specimen Banks ; Incidence ; *Immune System Diseases ; }, abstract = {OBJECTIVE: The occurrence of immune-mediated diseases (IMDs) in amyotrophic lateral sclerosis (ALS) patients is widely reported. However, whether IMDs and ALS is a simple coexistence or if there exists causal relationships between the two has been a subject of great interest to researchers.

METHODS: A total of 454,444 participants from the prospective cohort of UK Biobank were recruited to investigate the longitudinal association between IMDs and ALS. Previously any IMDs and organ specific IMDs were analyzed in relation to the following incident ALS by Cox-proportional hazard models. Subgroup analyses were performed to explore the covariates of these relationships.

RESULTS: After adjusting for potential covariates, the multivariate analysis showed that any IMDs were associated with an increased risk of ALS incidence (HR:1.42, 95%CI:1.03-1.94). IMDs of the endocrine-system and the intestinal-system were associated with increased risk of ALS incidence (endocrine-system IMDs: HR:3.01, 95%CI:1.49-6.06; intestinal system IMDs: HR:2.07, 95%CI: 1.14-3.77). Subgroup analyses revealed that immune burden, including IMD duration and the severity of inflammation had specific effects on the IMD-ALS association. In participants with IMD duration≥10 years or CRP≥1.3mg/L or females, previous IMDs increased the risk of incident ALS; however, in participants with IMD duration <10 years or CRP<1.3mg/L or males, IMDs had no effect on incident ALS.

INTERPRETATION: Our study provides evidence that previous any IMDs and endocrine-system and the intestinal-system specific IMDs are associated with an increased risk of developing ALS in females, but not in males.}, } @article {pmid38504632, year = {2024}, author = {Higashihara, M and Pavey, N and Menon, P and van den Bos, M and Shibuya, K and Kuwabara, S and Kiernan, MC and Koinuma, M and Vucic, S}, title = {Reduction in short interval intracortical inhibition from the early stage reflects the pathophysiology in amyotrophic lateral sclerosis: A meta-analysis study.}, journal = {European journal of neurology}, volume = {31}, number = {7}, pages = {e16281}, pmid = {38504632}, issn = {1468-1331}, mesh = {*Amyotrophic Lateral Sclerosis/physiopathology ; Humans ; *Transcranial Magnetic Stimulation ; *Neural Inhibition/physiology ; *Motor Cortex/physiopathology ; Evoked Potentials, Motor/physiology ; }, abstract = {BACKGROUND AND PURPOSE: Cortical hyperexcitability has been identified as a diagnostic and pathogenic biomarker of amyotrophic lateral sclerosis (ALS). Cortical excitability is assessed by transcranial magnetic stimulation (TMS), a non-invasive neurophysiological technique. The TMS biomarkers exhibiting highest sensitivity for cortical hyperexcitability in ALS remain to be elucidated. A meta-analysis was performed to determine the TMS biomarkers exhibiting the highest sensitivity for cortical hyperexcitability in ALS.

METHODS: A systematic literature review was conducted of all relevant studies published in the English language by searching PubMed, MEDLINE, Embase and Scopus electronic databases from 1 January 2006 to 28 February 2023. Inclusion criteria included studies reporting the utility of threshold tracking TMS (serial ascending method) in ALS and controls.

RESULTS: In total, more than 2500 participants, incorporating 1530 ALS patients and 1102 controls (healthy, 907; neuromuscular, 195) were assessed with threshold tracking TMS across 25 studies. Significant reduction of mean short interval intracortical inhibition (interstimulus interval 1-7 ms) exhibited the highest standardized mean difference with moderate heterogeneity (-0.994, 95% confidence interval -1.12 to -0.873, p < 0.001; Q = 38.61, p < 0.05; I[2] = 40%). The reduction of cortical silent period duration along with an increase in motor evoked potential amplitude and intracortical facilitation also exhibited significant, albeit smaller, standardized mean differences.

CONCLUSION: This large meta-analysis study disclosed that mean short interval intracortical inhibition reduction exhibited the highest sensitivity for cortical hyperexcitability in ALS. Combined findings from this meta-analysis suggest that research strategies aimed at understanding the cause of inhibitory interneuronal circuit dysfunction could enhance understanding of ALS pathogenesis.}, } @article {pmid38504592, year = {2024}, author = {Hamilton, HL and Akther, M and Anis, S and Colwell, CB and Vargas, MR and Pehar, M}, title = {Nicotinamide Adenine Dinucleotide Precursor Supplementation Modulates Neurite Complexity and Survival in Motor Neurons from Amyotrophic Lateral Sclerosis Models.}, journal = {Antioxidants & redox signaling}, volume = {41}, number = {7-9}, pages = {573-589}, pmid = {38504592}, issn = {1557-7716}, support = {R01 NS089640/NS/NINDS NIH HHS/United States ; R01 NS100835/NS/NINDS NIH HHS/United States ; }, mesh = {*Amyotrophic Lateral Sclerosis/metabolism/genetics/pathology ; Animals ; *Motor Neurons/metabolism/pathology/drug effects ; Mice ; Humans ; *Disease Models, Animal ; *NAD/metabolism ; *Induced Pluripotent Stem Cells/metabolism/cytology ; *Neurites/metabolism/drug effects ; Superoxide Dismutase-1/genetics/metabolism ; Mice, Transgenic ; Nicotinamide Mononucleotide/pharmacology/metabolism ; Neuroprotective Agents/pharmacology ; DNA-Binding Proteins/metabolism/genetics ; Cell Survival/drug effects ; Dietary Supplements ; }, abstract = {Aims: Increasing nicotinamide adenine dinucleotide (NAD[+]) availability has been proposed as a therapeutic approach to prevent neurodegeneration in amyotrophic lateral sclerosis (ALS). Accordingly, NAD[+] precursor supplementation appears to exert neuroprotective effects in ALS patients and mouse models. The mechanisms mediating neuroprotection remain uncertain but could involve changes in multiple cell types. We investigated a potential direct effect of the NAD[+] precursor nicotinamide mononucleotide (NMN) on the health of cultured induced pluripotent stem cell (iPSC)-derived human motor neurons and in motor neurons isolated from two ALS mouse models, that is, mice overexpressing wild-type transactive response DNA binding protein-43 (TDP-43) or the ALS-linked human superoxide dismutase 1 with the G93A mutation (hSOD1[G93A]). Results: NMN treatment increased the complexity of neuronal processes in motor neurons isolated from both mouse models and in iPSC-derived human motor neurons. In addition, NMN prevented neuronal death induced by trophic factor deprivation. In mouse and human motor neurons expressing ALS-linked mutant superoxide dismutase 1, NMN induced an increase in glutathione levels, but this effect was not observed in nontransgenic or TDP-43 overexpressing motor neurons. In contrast, NMN treatment normalized the TDP-43 cytoplasmic mislocalization induced by its overexpression. Innovation: NMN can directly act on motor neurons to increase the growth and complexity of neuronal processes and prevent the death induced by trophic factor deprivation. Conclusion: Our results support a direct beneficial effect of NAD[+] precursor supplementation on the maintenance of the neuritic arbor in motor neurons. Importantly, this was observed in motor neurons isolated from two different ALS models, with and without involvement of TDP-43 pathology, supporting its therapeutic potential in sporadic and familial ALS. Antioxid. Redox Signal. 41, 573-589.}, } @article {pmid38504285, year = {2024}, author = {Papaiz, F and Dourado, MET and de Medeiros Valentim, RA and Pinto, R and de Morais, AHF and Arrais, JP}, title = {Ensemble-imbalance-based classification for amyotrophic lateral sclerosis prognostic prediction: identifying short-survival patients at diagnosis.}, journal = {BMC medical informatics and decision making}, volume = {24}, number = {1}, pages = {80}, pmid = {38504285}, issn = {1472-6947}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/drug therapy ; Prognosis ; Machine Learning ; }, abstract = {Prognosticating Amyotrophic Lateral Sclerosis (ALS) presents a formidable challenge due to patients exhibiting different onset sites, progression rates, and survival times. In this study, we have developed and evaluated Machine Learning (ML) algorithms that integrate Ensemble and Imbalance Learning techniques to classify patients into Short and Non-Short survival groups based on data collected during diagnosis. We aimed to identify individuals at high risk of mortality within 24 months of symptom onset through analysis of patient data commonly encountered in daily clinical practice. Our Ensemble-Imbalance approach underwent evaluation employing six ML algorithms as base classifiers. Remarkably, our results outperformed those of individual algorithms, achieving a Balanced Accuracy of 88% and a Sensitivity of 96%. Additionally, we used the Shapley Additive Explanations framework to elucidate the decision-making process of the top-performing model, pinpointing the most important features and their correlations with the target prediction. Furthermore, we presented helpful tools to visualize and compare patient similarities, offering valuable insights. Confirming the obtained results, our approach could aid physicians in devising personalized treatment plans at the time of diagnosis or serve as an inclusion/exclusion criterion in clinical trials.}, } @article {pmid38503116, year = {2024}, author = {Opitz, DL}, title = {Editorial: Re-enchanting the vocation of science.}, journal = {Endeavour}, volume = {48}, number = {1}, pages = {100920}, doi = {10.1016/j.endeavour.2024.100920}, pmid = {38503116}, issn = {1873-1929}, mesh = {Occupations ; Retirement ; *Science ; }, abstract = {This editorial introduces the collection, "Specialists with Spirit: Re-Enchanting the Vocation of Science," co-edited by Dorien Daling and Hanneke Hoekstra. The collection offers a tribute to the eminent historian of science, Klaas van Berkel, commemorating his retirement from the University of Groningen. The papers compel us to consider the ongoing tensions between knowledge production and the social, political, and economic constraints faced by scholars, a theme that Max Weber famously addressed in his 1917 lecture, Wissenschaft als Beruf, which the collection's contributors revisit as they consider a range of historical and contemporary questions concerning science and its study by historians.}, } @article {pmid38501453, year = {2024}, author = {Erb, MK and Calcagno, N and Brown, R and Burke, KM and Scheier, ZA and Iyer, AS and Clark, A and Higgins, MP and Keegan, M and Gupta, AS and Johnson, SA and Chew, S and Berry, JD}, title = {Longitudinal comparison of the self-administered ALSFRS-RSE and ALSFRS-R as functional outcome measures in ALS.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {25}, number = {5-6}, pages = {570-580}, doi = {10.1080/21678421.2024.2322549}, pmid = {38501453}, issn = {2167-9223}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/physiopathology/psychology ; Male ; Female ; Longitudinal Studies ; Middle Aged ; Aged ; Self Report ; Outcome Assessment, Health Care/methods ; Smartphone ; Mobile Applications ; Adult ; }, abstract = {OBJECTIVE: Test the feasibility, adherence rates and optimal frequency of digital, remote assessments using the ALSFRS-RSE via a customized smartphone-based app.

METHODS: This fully remote, longitudinal study was conducted over a 24-week period, with virtual visits every 3 months and weekly digital assessments. 19 ALS participants completed digital assessments via smartphone, including a digital version of the ALSFRS-RSE and mood survey. Interclass correlation coefficients (ICC) and Bland-Altman plots were used to assess agreement between staff-administered and self-reported ALSFRS-R pairs. Longitudinal change was evaluated using ANCOVA models and linear mixed models, including impact of mood and time of day. Impact of frequency of administration of the ALSFRS-RSE on precision of the estimate slope was tested using a mixed effects model.

RESULTS: In our ALS cohort, digital assessments were well-accepted and adherence was robust, with completion rates of 86%. There was excellent agreement between the digital self-entry and staff-administered scores computing multiple ICCs (ICC range = 0.925-0.961), with scores on the ALSFRS-RSE slightly higher (1.304 points). Digital assessments were associated with increased precision of the slope, resulting in higher standardized response mean estimates for higher frequencies, though benefit appeared to diminish at biweekly and weekly frequency. Effects of participant mood and time of day on total ALSFRS-RSE score were evaluated but were minimal and not statistically significant.

CONCLUSION: Remote collection of digital patient-reported outcomes of functional status such as the ALSFRS-RSE yield more accurate estimates of change over time and provide a broader understanding of the lived experience of people with ALS.}, } @article {pmid38500808, year = {2024}, author = {, }, title = {Retraction: CSF p-tau as a potential cognition impairment biomarker in ALS.}, journal = {Frontiers in neurology}, volume = {15}, number = {}, pages = {1392563}, doi = {10.3389/fneur.2024.1392563}, pmid = {38500808}, issn = {1664-2295}, abstract = {[This retracts the article DOI: 10.3389/fneur.2022.991143.].}, } @article {pmid38500677, year = {2024}, author = {Zhou, L and Xu, R}, title = {Invertebrate genetic models of amyotrophic lateral sclerosis.}, journal = {Frontiers in molecular neuroscience}, volume = {17}, number = {}, pages = {1328578}, pmid = {38500677}, issn = {1662-5099}, abstract = {Amyotrophic lateral sclerosis (ALS) is a common adult-onset neurodegenerative disease characterized by the progressive death of motor neurons in the cerebral cortex, brain stem, and spinal cord. The exact mechanisms underlying the pathogenesis of ALS remain unclear. The current consensus regarding the pathogenesis of ALS suggests that the interaction between genetic susceptibility and harmful environmental factors is a promising cause of ALS onset. The investigation of putative harmful environmental factors has been the subject of several ongoing studies, but the use of transgenic animal models to study ALS has provided valuable information on the onset of ALS. Here, we review the current common invertebrate genetic models used to study the pathology, pathophysiology, and pathogenesis of ALS. The considerations of the usage, advantages, disadvantages, costs, and availability of each invertebrate model will also be discussed.}, } @article {pmid38499535, year = {2024}, author = {Chen, S and Puri, A and Bell, B and Fritsche, J and Palacios, HH and Balch, M and Sprunger, ML and Howard, MK and Ryan, JJ and Haines, JN and Patti, GJ and Davis, AA and Jackrel, ME}, title = {HTRA1 disaggregates α-synuclein amyloid fibrils and converts them into non-toxic and seeding incompetent species.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {2436}, pmid = {38499535}, issn = {2041-1723}, support = {R35 GM128772/GM/NIGMS NIH HHS/United States ; K08 NS101118/NS/NINDS NIH HHS/United States ; F31 NS120512/NS/NINDS NIH HHS/United States ; F31 GM140622/GM/NIGMS NIH HHS/United States ; }, mesh = {Humans ; *alpha-Synuclein/genetics/metabolism ; Amyloid/metabolism ; High-Temperature Requirement A Serine Peptidase 1/genetics/metabolism ; *Parkinson Disease/genetics/metabolism ; Lewy Bodies/metabolism ; }, abstract = {Parkinson's disease (PD) is closely linked to α-synuclein (α-syn) misfolding and accumulation in Lewy bodies. The PDZ serine protease HTRA1 degrades fibrillar tau, which is associated with Alzheimer's disease, and inactivating mutations to mitochondrial HTRA2 are implicated in PD. Here, we report that HTRA1 inhibits aggregation of α-syn as well as FUS and TDP-43, which are implicated in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. The protease domain of HTRA1 is necessary and sufficient for inhibiting aggregation, yet this activity is proteolytically-independent. Further, HTRA1 disaggregates preformed α-syn fibrils, rendering them incapable of seeding aggregation of endogenous α-syn, while reducing HTRA1 expression promotes α-syn seeding. HTRA1 remodels α-syn fibrils by targeting the NAC domain, the key domain catalyzing α-syn amyloidogenesis. Finally, HTRA1 detoxifies α-syn fibrils and prevents formation of hyperphosphorylated α-syn accumulations in primary neurons. Our findings suggest that HTRA1 may be a therapeutic target for a range of neurodegenerative disorders.}, } @article {pmid38499486, year = {2024}, author = {Jia, J and Fan, H and Wan, X and Fang, Y and Li, Z and Tang, Y and Zhang, Y and Huang, J and Fang, D}, title = {FUS reads histone H3K36me3 to regulate alternative polyadenylation.}, journal = {Nucleic acids research}, volume = {52}, number = {10}, pages = {5549-5571}, pmid = {38499486}, issn = {1362-4962}, support = {2022YFA1302800//National Key R&D Program of China/ ; 32361133547//National Natural Science Foundation of China/ ; 2019QN81005//Fundamental Research Funds for the Central Universities/ ; LZ24C060001//Natural Science Foundation of China/ ; 2022SKLS-KFKT002//Shanghai Jiao Tong University School of Medicine/ ; }, mesh = {Animals ; Humans ; Mice ; Amyotrophic Lateral Sclerosis/genetics/metabolism ; Cell Differentiation/genetics ; Chromatin/metabolism/genetics ; HEK293 Cells ; *Histones/metabolism/genetics ; Mitochondria/metabolism/genetics ; Mouse Embryonic Stem Cells ; Mutation ; *Polyadenylation/genetics ; *RNA-Binding Protein FUS/genetics/metabolism ; Cell Line ; Protein Domains ; }, abstract = {Complex organisms generate differential gene expression through the same set of DNA sequences in distinct cells. The communication between chromatin and RNA regulates cellular behavior in tissues. However, little is known about how chromatin, especially histone modifications, regulates RNA polyadenylation. In this study, we found that FUS was recruited to chromatin by H3K36me3 at gene bodies. The H3K36me3 recognition of FUS was mediated by the proline residues in the ZNF domain. After these proline residues were mutated or H3K36me3 was abolished, FUS dissociated from chromatin and bound more to RNA, resulting in an increase in polyadenylation sites far from stop codons genome-wide. A proline mutation corresponding to a mutation in amyotrophic lateral sclerosis contributed to the hyperactivation of mitochondria and hyperdifferentiation in mouse embryonic stem cells. These findings reveal that FUS is an H3K36me3 reader protein that links chromatin-mediated alternative polyadenylation to human disease.}, } @article {pmid38499333, year = {2024}, author = {Turner, MR}, title = {We need to talk about brain donation.}, journal = {Practical neurology}, volume = {24}, number = {3}, pages = {183-184}, doi = {10.1136/pn-2024-004102}, pmid = {38499333}, issn = {1474-7766}, mesh = {Humans ; *Tissue and Organ Procurement ; Tissue Donors ; Brain/diagnostic imaging ; Brain Death/diagnosis ; }, } @article {pmid38499161, year = {2024}, author = {Bashir, S and Aiman, A and Shahid, M and Chaudhary, AA and Sami, N and Basir, SF and Hassan, I and Islam, A}, title = {Amyloid-induced neurodegeneration: A comprehensive review through aggregomics perception of proteins in health and pathology.}, journal = {Ageing research reviews}, volume = {96}, number = {}, pages = {102276}, doi = {10.1016/j.arr.2024.102276}, pmid = {38499161}, issn = {1872-9649}, mesh = {Humans ; Amyloid/metabolism ; *Amyloidosis/metabolism ; *Neurodegenerative Diseases/metabolism ; *Parkinson Disease/metabolism ; Amyloidogenic Proteins ; Perception ; }, abstract = {Amyloidosis of protein caused by fibrillation and aggregation are some of the most exciting new edges not only in protein sciences but also in molecular medicines. The present review discusses recent advancements in the field of neurodegenerative diseases and therapeutic applications with ongoing clinical trials, featuring new areas of protein misfolding resulting in aggregation. The endogenous accretion of protein fibrils having fibrillar morphology symbolizes the beginning of neuro-disorders. Prognostic amyloidosis is prominent in numerous degenerative infections such as Alzheimer's and Parkinson's disease, Amyotrophic lateral sclerosis (ALS), etc. However, the molecular basis determining the intracellular or extracellular evidence of aggregates, playing a significant role as a causative factor in neurodegeneration is still unclear. Structural conversions and protein self-assembly resulting in the formation of amyloid oligomers and fibrils are important events in the pathophysiology of the disease. This comprehensive review sheds light on the evolving landscape of potential treatment modalities, highlighting the ongoing clinical trials and the potential socio-economic impact of novel therapeutic interventions in the realm of neurodegenerative diseases. Furthermore, many drugs are undergoing different levels of clinical trials that would certainly help in treating these disorders and will surely improve the socio-impact of human life.}, } @article {pmid38498721, year = {2024}, author = {Kertesz, A and Finger, E and Munoz, DG}, title = {Progress in Primary Progressive Aphasia: A Review.}, journal = {Cognitive and behavioral neurology : official journal of the Society for Behavioral and Cognitive Neurology}, volume = {37}, number = {1}, pages = {3-12}, pmid = {38498721}, issn = {1543-3641}, mesh = {Humans ; *Frontotemporal Dementia/diagnosis/genetics ; *Supranuclear Palsy, Progressive/genetics/pathology ; Syndrome ; *Aphasia, Primary Progressive ; }, abstract = {We present a review of the definition, classification, and epidemiology of primary progressive aphasia (PPA); an update of the taxonomy of the clinical syndrome of PPA; and recent advances in the neuroanatomy, pathology, and genetics of PPA, as well as the search for biomarkers and treatment. PPA studies that have contributed to concepts of language organization and disease propagation in neurodegeneration are also reviewed. In addition, the issues of heterogeneity versus the relationships of the clinical phenotypes and their relationship to biological, pathological, and genetic advances are discussed, as is PPA's relationship to other conditions such as frontotemporal dementia, corticobasal degeneration, progressive supranuclear palsy, Pick disease, and amyotrophic lateral sclerosis. Arguments are presented in favor of considering these conditions as one entity versus many.}, } @article {pmid38498118, year = {2024}, author = {Khanna, RK and Catanese, S and Blasco, H and Pisella, PJ and Corcia, P}, title = {Corneal nerves and amyotrophic lateral sclerosis: an in vivo corneal confocal imaging study.}, journal = {Journal of neurology}, volume = {271}, number = {6}, pages = {3370-3377}, pmid = {38498118}, issn = {1432-1459}, support = {2021//Association pour la Recherche sur la Sclérose Latérale Amyotrophique et autres Maladies du Motoneurone/ ; 2021//Novartis-Société Française d'Ophtalmologie./ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnostic imaging/pathology/physiopathology ; *Microscopy, Confocal ; Male ; *Cornea/innervation/diagnostic imaging/pathology ; Female ; Middle Aged ; Aged ; Case-Control Studies ; Prospective Studies ; Nerve Fibers/pathology ; Adult ; }, abstract = {OBJECTIVES: Amyotrophic lateral sclerosis (ALS) is a severe motor neuron disorder. Diagnosis is challenging due to its clinical heterogeneity and the absence of definitive diagnostic tools, leading to delays averaging between 9.1 and 27 months. In vivo corneal confocal microscopy, assessing the sub-basal nerve plexus of the cornea, has been proposed as a potential biomarker for ALS. We aimed to determine whether the assessment of corneal nerves using in vivo confocal microscopy can serve as an imaging biomarker for ALS.

METHODS: A single-centre prospective case-control study was conducted in France from September 2021 to March 2023 including patients with ALS according to the revised EI Escorial criteria. The corneal sub-basal nerve plexus was analysed using in vivo confocal microscopy. An automated algorithm (ACCMetrics) was used to evaluate corneal parameters: nerve fibre density, nerve branch density, nerve fibre length, nerve fibre area, nerve total branch density, nerve fibre width, and nerve fractal dimension.

RESULTS: Twenty-two patients with ALS and 30 controls were included. No significant differences were found between ALS and control groups for all corneal parameters (p > 0.05). Corneal sensitivity did not differ between groups, and no correlation was identified between corneal nerve parameters and ALS disease duration, severity and rate of progression (p > 0.05).

CONCLUSIONS: The present study does not support the use of in vivo corneal confocal microscopy as an early diagnostic or prognostic tool for ALS. Further research, especially longitudinal investigations, is needed to understand any potential corneal innervation changes as ALS progresses.}, } @article {pmid38496572, year = {2024}, author = {Cameron, B and Torres-Hernandez, L and Montague, VL and Lewis, KA and Smith, H and Fox, J and Guo, X and Kalb, RG and George, L}, title = {Titin is a nucleolar protein in neurons.}, journal = {Research square}, volume = {}, number = {}, pages = {}, pmid = {38496572}, issn = {2693-5015}, support = {P20 GM103474/GM/NIGMS NIH HHS/United States ; R15 NS090384/NS/NINDS NIH HHS/United States ; }, abstract = {Titin is the largest protein produced by living cells and its function as a molecular spring in striated muscle is well characterized (1, 2). Here we demonstrate that titin isoforms in the same size range as found in muscle are prominent neuronal proteins in both the central and peripheral nervous systems, including motor neurons in the spinal cord and brain. Within these neurons, titin localizes to the dense fibrillar component of the nucleolus, the site of ribosomal RNA biogenesis and modification, and a critical site of dysfunction in neurodegenerative disease (3-5). Additionally, we show that the levels of both titin mRNA and protein are altered in the spinal cord of SOD1[G93A] mice, a commonly used model of amyotrophic lateral sclerosis, indicating that titin mediated nucleolar events may in fact contribute to the pathobiology of disease.}, } @article {pmid38496415, year = {2024}, author = {Suazo, KF and Mishra, V and Maity, S and Auger, SA and Justyna, K and Petre, A and Ottoboni, L and Ongaro, J and Corti, SP and Lotti, F and Przedborski, S and Distefano, MD}, title = {Improved synthesis and application of an alkyne-functionalized isoprenoid analogue to study the prenylomes of motor neurons, astrocytes and their stem cell progenitors.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {38496415}, issn = {2692-8205}, support = {R01 NS107442/NS/NINDS NIH HHS/United States ; P30 CA077598/CA/NCI NIH HHS/United States ; R21 NS101575/NS/NINDS NIH HHS/United States ; T32 AG029796/AG/NIA NIH HHS/United States ; T32 GM132029/GM/NIGMS NIH HHS/United States ; R35 GM141853/GM/NIGMS NIH HHS/United States ; }, abstract = {Protein prenylation is one example of a broad class of post-translational modifications where proteins are covalently linked to various hydrophobic moieties. To globally identify and monitor levels of all prenylated proteins in a cell simultaneously, our laboratory and others have developed chemical proteomic approaches that rely on the metabolic incorporation of isoprenoid analogues bearing bio-orthogonal functionality followed by enrichment and subsequent quantitative proteomic analysis. Here, several improvements in the synthesis of the alkyne-containing isoprenoid analogue C15AlkOPP are reported to improve synthetic efficiency. Next, metabolic labeling with C15AlkOPP was optimized to obtain useful levels of metabolic incorporation of the probe in several types of primary cells. Those conditions were then used to study the prenylomes of motor neurons (ES-MNs), astrocytes (ES-As), and their embryonic stem cell progenitors (ESCs), which allowed for the identification of 54 prenylated proteins from ESCs, 50 from ES-MNs and 84 from ES-As, representing all types of prenylation. Bioinformatic analysis revealed specific enriched pathways, including nervous system development, chemokine signaling, Rho GTPase signaling, and adhesion. Hierarchical clustering showed that most enriched pathways in all three cell types are related to GTPase activity and vesicular transport. In contrast, STRING analysis showed significant interactions in two populations that appear to be cell type dependent. The data provided herein demonstrates that robust incorporation of C15AlkOPP can be obtained in ES-MNs and related primary cells purified via magnetic-activated cell sorting allowing the identification and quantification of numerous prenylated proteins. These results suggest that metabolic labeling with C15AlkOPP should be an effective approach for investigating the role of prenylated proteins in primary cells in both normal cells and disease pathologies, including ALS.}, } @article {pmid38496202, year = {2024}, author = {da Silva Alves, C and Barroso, T and Gerardo, A and Almeida, T and Maduro, S and Boléo-Tomé, JP and Liberato, H}, title = {Forced Expiratory Volume in One Second Quotient (FEV1Q) as a Prognostic Factor in Amyotrophic Lateral Sclerosis Patients: Comparing Its Predictive Value to Other Lung Function Measurements.}, journal = {Cureus}, volume = {16}, number = {2}, pages = {e54176}, pmid = {38496202}, issn = {2168-8184}, abstract = {INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder affecting the first and second motor neurons. Forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) have conventionally served as indicators of respiratory muscle strength. Recently, FEV1Q (FEV1 divided by the sex-specific first percentile values of absolute FEV1 in adults with lung disease) has been suggested as a predictor of mortality. While FVC has been utilized as a prognostic factor, FEV1Q has not yet been examined.

METHODS: This retrospective unicenter study evaluated FEV1Q as a predictor of mortality in ALS patients, comparing its predictive efficacy with other measurements, including FEV1, FVC, sniff nasal inspiratory pressure, and maximal inspiratory pressure. The study utilized univariate analysis for each variable employing the Cox proportional hazards model to determine the statistical significance and predictive power of each measurement.

RESULTS: Forty-five patients were included, female predominant (60%) and an average age at diagnosis of 69.2 ± 11 years. Almost all (95%) met the criteria for non-invasive ventilation (NIV) and initiated (93%) during the study period, a mean of 137 days after diagnosis. The mortality rate observed was 57%, occurring at a median of 398 days post-diagnosis. On average, patients underwent 1.7 pulmonary function tests, revealing a decline in various parameters, including FEV1, FEV1Q, and FVC. However, only FEV1Q was a statistically significant predictor of mortality (p < 0.0083) in a Cox regression analysis. A negative coefficient for FEV1Q indicated that higher values were associated with a reduced mortality risk, with an average FEV1Q of 2.68 observed at the time of death.

CONCLUSION: FEV1Q emerged as the only statistically significant predictor of mortality among the evaluated respiratory measurements in ALS patients. This study is the first to focus on applying FEV1Q in the clinical evaluation of ALS, marking an initial step in understanding its potential role in patient follow-up. However, further studies are needed before these findings can be incorporated into clinical practice.}, } @article {pmid38495583, year = {2024}, author = {Uy, G and Farrell, LN and Faheem, SF and Kinne, LE and Adore, MG and Im, SH and Fairman, R}, title = {The Effects of poly-GA and poly-PR C9orf72 Dipeptide Repeats on Sleep Patterns in Drosophila melanogaster.}, journal = {microPublication biology}, volume = {2024}, number = {}, pages = {}, pmid = {38495583}, issn = {2578-9430}, abstract = {C9orf72 is the most common familial gene associated with amyotrophic lateral sclerosis (ALS). Dipeptide repeats (DPRs) encoded by an expanded nucleotide repeat sequence in the C9orf72 gene were found in the sleep-related neurons of patients, indicating a role of DPRs in ALS-associated sleep disruptions. Poly-GA or poly-PR DPRs were expressed in male Drosophila melanogaster to study their effect on sleep . Poly-PR expression caused sleep disruptions while poly-GA expression did not. This study validates the use of Drosophila as an in vivo model system for exploring the roles of DPRs in perturbing the underlying molecular mechanisms in sleep regulation.}, } @article {pmid38493058, year = {2024}, author = {Milani, M and Della Valle, I and Rossi, S and Fabbrizio, P and Margotta, C and Nardo, G and Cozzolino, M and D'Ambrosi, N and Apolloni, S}, title = {Neuroprotective effects of niclosamide on disease progression via inflammatory pathways modulation in SOD1-G93A and FUS-associated amyotrophic lateral sclerosis models.}, journal = {Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics}, volume = {21}, number = {3}, pages = {e00346}, pmid = {38493058}, issn = {1878-7479}, mesh = {Animals ; Mice ; *Amyotrophic Lateral Sclerosis/drug therapy/genetics/pathology ; Disease Models, Animal ; *Disease Progression ; Inflammation/drug therapy ; Mice, Transgenic ; *Neuroprotective Agents/pharmacology/therapeutic use ; *Niclosamide/pharmacology/therapeutic use ; RNA-Binding Protein FUS/genetics/metabolism ; Superoxide Dismutase-1/genetics/metabolism ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a complex neurodegenerative disease influenced by genetic, epigenetic, and environmental factors, resulting in dysfunction in cellular and molecular pathways. The limited efficacy of current treatments highlights the need for combination therapies targeting multiple aspects of the disease. Niclosamide, an anthelminthic drug listed as an essential medicine, has been repurposed in clinical trials for different diseases due to its anti-inflammatory and anti-fibrotic properties. Niclosamide can inhibit various molecular pathways (e.g., STAT3, mTOR) that are dysregulated in ALS, suggesting its potential to disrupt these altered mechanisms associated with the pathology. We administered niclosamide intraperitoneally to two transgenic murine models, SOD1-G93A and FUS mice, mimicking key pathological processes of ALS. The treatment was initiated at the onset of symptoms, and we assessed disease progression by neurological scores, rotarod and wire tests, and monitored survival. Furthermore, we investigated cellular and molecular mechanisms affected by niclosamide in the spinal cord and muscle of ALS mice. In both models, the administration of niclosamide resulted in a slowdown of disease progression, an increase in survival rates, and an improvement in tissue pathology. This was characterised by reduced gliosis, motor neuron loss, muscle atrophy, and inflammatory pathways. Based on these results, our findings demonstrate that niclosamide can impact multiple pathways involved in ALS. This multi-targeted approach leads to a slowdown in the progression of the disease, positioning niclosamide as a promising candidate for repurposing in the treatment of ALS.}, } @article {pmid38492239, year = {2024}, author = {Johnson, CN and Sojitra, KA and Sohn, EJ and Moreno-Romero, AK and Baudin, A and Xu, X and Mittal, J and Libich, DS}, title = {Insights into Molecular Diversity within the FUS/EWS/TAF15 Protein Family: Unraveling Phase Separation of the N-Terminal Low-Complexity Domain from RNA-Binding Protein EWS.}, journal = {Journal of the American Chemical Society}, volume = {146}, number = {12}, pages = {8071-8085}, pmid = {38492239}, issn = {1520-5126}, support = {R01 GM136917/GM/NIGMS NIH HHS/United States ; R01 GM140127/GM/NIGMS NIH HHS/United States ; R35 GM153388/GM/NIGMS NIH HHS/United States ; }, mesh = {Humans ; RNA-Binding Protein EWS/metabolism ; RNA-Binding Protein FUS/metabolism ; Phase Separation ; *Sarcoma, Ewing/genetics/metabolism/pathology ; Proteins/metabolism ; Tyrosine ; *TATA-Binding Protein Associated Factors/genetics/metabolism ; }, abstract = {The FET protein family, comprising FUS, EWS, and TAF15, plays crucial roles in mRNA maturation, transcriptional regulation, and DNA damage response. Clinically, they are linked to Ewing family tumors and neurodegenerative diseases such as amyotrophic lateral sclerosis. The fusion protein EWS::FLI1, the causative mutation of Ewing sarcoma, arises from a genomic translocation that fuses a portion of the low-complexity domain (LCD) of EWS (EWS[LCD]) with the DNA binding domain of the ETS transcription factor FLI1. This fusion protein modifies transcriptional programs and disrupts native EWS functions, such as splicing. The exact role of the intrinsically disordered EWS[LCD] remains a topic of active investigation, but its ability to phase separate and form biomolecular condensates is believed to be central to EWS::FLI1's oncogenic properties. Here, we used paramagnetic relaxation enhancement NMR, microscopy, and all-atom molecular dynamics (MD) simulations to better understand the self-association and phase separation tendencies of the EWS[LCD]. Our NMR data and mutational analysis suggest that a higher density and proximity of tyrosine residues amplify the likelihood of condensate formation. MD simulations revealed that the tyrosine-rich termini exhibit compact conformations with unique contact networks and provided critical input on the relationship between contacts formed within a single molecule (intramolecular) and inside the condensed phase (intermolecular). These findings enhance our understanding of FET proteins' condensate-forming capabilities and underline differences between EWS, FUS, and TAF15.}, } @article {pmid38491246, year = {2024}, author = {Musarò, A and Dobrowolny, G and Cambieri, C and Libonati, L and Moret, F and Casola, I and Laurenzi, G and Garibaldi, M and Inghilleri, M and Ceccanti, M}, title = {MiR206 and 423-3p Are Differently Modulated in Fast and Slow-Progressing Amyotrophic Lateral Sclerosis Patients.}, journal = {Neuromolecular medicine}, volume = {26}, number = {1}, pages = {5}, pmid = {38491246}, issn = {1559-1174}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics ; Disease Progression ; *MicroRNAs/genetics ; Research Design ; Biomarkers ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a rare neuromuscular disease with a wide disease progression. Despite several efforts to develop efficient biomarkers, many concerns about the available ones still need to be addressed. MicroRNA (miR) are non-coding RNAs that can modulate molecular circuits and are involved in ALS pathogenic mechanisms. 22 fast and 23 slow-progressing-defined ALS patients were recruited. ALSFRS-R, strength, respiratory function, nerve conduction studies, and creatine kinase were evaluated at the baseline and after 6 months of follow-up. The mean monthly reduction of the previous variables (progression index - PI) was calculated. MiR206, 133a-3p, 151a-5p, 199a-5p, and 423-3p were dosed. The univariate analysis showed an independent reduction of miR206 and an increase of miR423-3p in patients with a slow slope of ALSFRS-R and weakness, respectively. MiR206 and 423-3p are differently modulated in fast and slow-progressing ALS patients, suggesting a role for microRNAs in prognosis and therapeutic target.}, } @article {pmid38491210, year = {2024}, author = {He, D and Yang, X and Liu, L and Shen, D and Liu, Q and Liu, M and Zhang, X and Cui, L}, title = {Dysregulated N[6]-methyladenosine modification in peripheral immune cells contributes to the pathogenesis of amyotrophic lateral sclerosis.}, journal = {Frontiers of medicine}, volume = {18}, number = {2}, pages = {285-302}, pmid = {38491210}, issn = {2095-0225}, mesh = {*Amyotrophic Lateral Sclerosis/genetics/immunology ; *Adenosine/analogs & derivatives/metabolism ; Humans ; Animals ; Female ; Mice ; Male ; Middle Aged ; Aged ; Case-Control Studies ; RAW 264.7 Cells ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurogenerative disorder with uncertain origins. Emerging evidence implicates N6-methyladenosine (m[6]A) modification in ALS pathogenesis. Methylated RNA immunoprecipitation sequencing (MeRIP-seq) and liquid chromatography-mass spectrometry were utilized for m[6]A profiling in peripheral immune cells and serum proteome analysis, respectively, in patients with ALS (n = 16) and controls (n = 6). The single-cell transcriptomic dataset (GSE174332) of primary motor cortex was further analyzed to illuminate the biological implications of differentially methylated genes and cell communication changes. Analysis of peripheral immune cells revealed extensive RNA hypermethylation, highlighting candidate genes with differential m[6]A modification and expression, including C-X3-C motif chemokine receptor 1 (CX3CR1). In RAW264.7 macrophages, disrupted CX3CR1 signaling affected chemotaxis, potentially influencing immune cell migration in ALS. Serum proteome analysis demonstrated the role of dysregulated immune cell migration in ALS. Cell type-specific expression variations of these genes in the central nervous system (CNS), particularly microglia, were observed. Intercellular communication between neurons and glial cells was selectively altered in ALS CNS. This integrated approach underscores m[6]A dysregulation in immune cells as a potential ALS contributor.}, } @article {pmid38490348, year = {2024}, author = {Chatterjee, A and Kumar, S and Roy Sarkar, S and Halder, R and Kumari, R and Banerjee, S and Sarkar, B}, title = {Dietary polyphenols represent a phytotherapeutic alternative for gut dysbiosis associated neurodegeneration: A systematic review.}, journal = {The Journal of nutritional biochemistry}, volume = {129}, number = {}, pages = {109622}, doi = {10.1016/j.jnutbio.2024.109622}, pmid = {38490348}, issn = {1873-4847}, mesh = {*Polyphenols/pharmacology ; *Dysbiosis/drug therapy ; *Gastrointestinal Microbiome/drug effects ; Humans ; *Neurodegenerative Diseases/drug therapy ; Animals ; Oxidative Stress/drug effects ; Phytotherapy ; Prebiotics ; Diet ; }, abstract = {Globally, neurodegeneration and cerebrovascular disease are common and growing causes of morbidity and mortality. Pathophysiology of this group of diseases encompasses various factors from oxidative stress to gut microbial dysbiosis. The study of the etiology and mechanisms of oxidative stress as well as gut dysbiosis-induced neurodegeneration in Alzheimer's disease, Parkinson's disease, multiple sclerosis, amyotrophic lateral sclerosis, autism spectrum disorder, and Huntington's disease has recently received a lot of attention. Numerous studies lend credence to the notion that changes in the intestinal microbiota and enteric neuroimmune system have an impact on the initiation and severity of these diseases. The prebiotic role of polyphenols can influence the makeup of the gut microbiota in neurodegenerative disorders by modulating intracellular signalling pathways. Metabolites of polyphenols function directly as neurotransmitters by crossing the blood-brain barrier or indirectly via influencing the cerebrovascular system. This assessment aims to bring forth an interlink between the consumption of polyphenols biotransformed by gut microbiota which in turn modulate the gut microbial diversity and biochemical changes in the brain. This systematic review will further augment research towards the association of dietary polyphenols in the management of gut dysbiosis-associated neurodegenerative diseases.}, } @article {pmid38490215, year = {2024}, author = {Reilich, P}, title = {[Multidimensional care for people with ALS and their families].}, journal = {Fortschritte der Neurologie-Psychiatrie}, volume = {92}, number = {3}, pages = {70-71}, doi = {10.1055/a-2240-8802}, pmid = {38490215}, issn = {1439-3522}, } @article {pmid38490025, year = {2024}, author = {Turco, A and Primiceri, E and Chiriacò, MS and La Pesa, V and Ferrara, F and Riva, N and Quattrini, A and Romano, A and Maruccio, G}, title = {Advancing amyotrophic lateral sclerosis disease diagnosis: A lab-on-chip electrochemical immunosensor for ultra-sensitive TDP-43 protein detection and monitoring in serum patients'.}, journal = {Talanta}, volume = {273}, number = {}, pages = {125866}, doi = {10.1016/j.talanta.2024.125866}, pmid = {38490025}, issn = {1873-3573}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/metabolism ; Polymers ; *Biosensing Techniques ; *Neurodegenerative Diseases ; Reproducibility of Results ; Immunoassay ; Pyrroles ; DNA-Binding Proteins/metabolism ; Biomarkers/metabolism ; }, abstract = {The global increase in population aging has led to a rise in neurodegenerative diseases (NDs), posing significant challenges to public health. Developing selective and specific biomarkers for early diagnosis and drug development is crucial addressing the growing burden of NDs. In this context, the RNA-binding protein TDP-43 has emerged as a promising biomarker for amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration (FTLD), and TDP-43-associated proteinopathies. However, existing detection methods suffer from limitations such as cost, complexity, and operator dependence. Here, we present a novel electrochemical biosensor integrated into a lab-on-chip (LoC) platform to detect TDP-43. The sensor utilizes electrosynthesized polypyrrole derivatives with carboxylic groups for transducer functionalization, enabling targeted immobilization of TDP-43 antibodies. Differential pulsed voltammetry (DPV) is used for the indirect detection and quantification of TDP-43. The chip exhibits rapid response, good reproducibility, a linear detection range, and sensitivity from 0.01 ng/mL to 25 ng/mL of TDP-43 protein concentration with a LOD = 10 pg/mL. Furthermore, successful TDP-43 detection in complex matrices like serum of ALS patients and healthy individuals demonstrates its potential as a point-of-care diagnostic device. This electrochemical biosensor integrated into a chip offers good sensitivity, rapid response, and robust performance, providing a promising avenue for advancing neurodegenerative disease diagnostics and therapeutic development.}, } @article {pmid38489867, year = {2024}, author = {Tausendfreund, O and Bidlingmaier, M and Martini, S and Müller, K and Rippl, M and Schilbach, K and Schmidmaier, R and Drey, M}, title = {Growth hormone treatment in aged patients with comorbidities: A systematic review.}, journal = {Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society}, volume = {75}, number = {}, pages = {101584}, doi = {10.1016/j.ghir.2024.101584}, pmid = {38489867}, issn = {1532-2238}, mesh = {Aged ; Humans ; Comorbidity ; Growth Hormone ; *Human Growth Hormone/adverse effects/therapeutic use ; Insulin-Like Growth Factor I ; Quality of Life ; Randomized Controlled Trials as Topic ; *Aging/pathology ; }, abstract = {OBJECTIVE: Hormonal substitution with growth hormone in aged patients remains a debated research topic and is rarely initiated in clinical practice. This reluctance may originate from concerns about adverse effects and the uncritical use as an anti-aging agent. Nevertheless, beneficial effects for selected patients suffering from certain acute and chronic illnesses could justify its use at an advanced age. This systematic review analyzes randomized controlled studies of GH interventions in older patients with different comorbidities to assess both, beneficial and harmful effects.

DESIGN: A systematic search strategy was implemented to identify relevant studies from PubMed, MEDLINE, and The Cochrane Library.

INCLUSION CRITERIA: participants aged over 65 years, randomized controlled trials involving human growth hormone (GH) and presence of at least one additional comorbidity independent of a flawed somatotropic axis.

RESULTS: The eight eligible studies encompassed various comorbidities including osteoporosis, frailty, chronic heart failure, hip fracture, amyotrophic lateral sclerosis and hemodialysis. Outcomes varied, including changes in body composition, physical performance, strength, bone mineral density, cardiovascular parameters, quality of life and housing situation. Study protocols differed greatly in GH application frequency (daily, 2nd day or 3×/week), doses (0.41 mg-2.6 mg; mean 1.3 mg per 60 kg patient) and duration (1-12 months; mean 7 months). Mild dose-related side effects were reported, alongside noticeable positive impacts particularly on body composition, functionality, and quality of life.

CONCLUSION: Despite limited evidence, GH treatment might offer diverse benefits with few adverse effects. Further research with IGF-I dependent indication and clear outcomes, incorporating IGF-I dependent GH titration in older adults is warranted.}, } @article {pmid38488546, year = {2024}, author = {Yang, Y and Cheng, Q and Gao, J and Kim, WS}, title = {Status of biomarker development for frontotemporal dementia and amyotrophic lateral sclerosis.}, journal = {Neural regeneration research}, volume = {19}, number = {10}, pages = {2117-2118}, pmid = {38488546}, issn = {1673-5374}, } @article {pmid38487578, year = {2024}, author = {Cortes-Flores, H and Torrandell-Haro, G and Brinton, RD}, title = {Association between CNS-active drugs and risk of Alzheimer's and age-related neurodegenerative diseases.}, journal = {Frontiers in psychiatry}, volume = {15}, number = {}, pages = {1358568}, pmid = {38487578}, issn = {1664-0640}, support = {P01 AG026572/AG/NIA NIH HHS/United States ; P30 AG072980/AG/NIA NIH HHS/United States ; R01 AG057931/AG/NIA NIH HHS/United States ; }, abstract = {OBJECTIVE: As neuropsychiatric conditions can increase the risk of age-related neurodegenerative diseases (NDDs), the impact of CNS-active drugs on the risk of developing Alzheimer's Disease (AD), non-AD dementia, Multiple Sclerosis (MS), Parkinson's Disease (PD) and Amyotrophic Lateral Sclerosis (ALS) was investigated.

RESEARCH DESIGN AND METHODS: A retrospective cohort analysis of a medical claims dataset over a 10 year span was conducted in patients aged 60 years or older. Participants were propensity score matched for comorbidity severity and demographic parameters. Relative risk (RR) ratios and 95% confidence intervals (CI) were determined for age-related NDDs. Cumulative hazard ratios and treatment duration were determined to assess the association between CNS-active drugs and NDDs at different ages and treatment duration intervals.

RESULTS: In 309,128 patients who met inclusion criteria, exposure to CNS-active drugs was associated with a decreased risk of AD (0.86% vs 1.73%, RR: 0.50; 95% CI: 0.47-0.53; p <.0001) and all NDDs (3.13% vs 5.76%, RR: 0.54; 95% CI: 0.53-0.56; p <.0001). Analysis of impact of drug class on risk of AD indicated that antidepressant, sedative, anticonvulsant, and stimulant medications were associated with significantly reduced risk of AD whereas atypical antipsychotics were associated with increased AD risk. The greatest risk reduction for AD and NDDs occurred in patients aged 70 years or older with a protective effect only in patients with long-term therapy (>3 years). Furthermore, responders to these therapeutics were characterized by diagnosed obesity and higher prescriptions of anti-inflammatory drugs and menopausal hormonal therapy, compared to patients with a diagnosis of AD (non-responders). Addition of a second CNS-active drug was associated with greater reduction in AD risk compared to monotherapy, with the combination of a Z-drug and an SNRI associated with greatest AD risk reduction.

CONCLUSION: Collectively, these findings indicate that CNS-active drugs were associated with reduced risk of developing AD and other age-related NDDs. The exception was atypical antipsychotics, which increased risk. Potential use of combination therapy with atypical antipsychotics could mitigate the risk conferred by these drugs. Evidence from these analyses advance precision prevention strategies to reduce the risk of age-related NDDs in persons with neuropsychiatric disorders.}, } @article {pmid38487377, year = {2024}, author = {Hirsch, AG and Wright, EA and Nordberg, CM and DeWalle, J and Stains, EL and Kennalley, AL and Zhang, J and Tusing, LD and Piper, BJ}, title = {Dispensaries and Medical Marijuana Certifications and Indications: Unveiling the Geographic Connections in Pennsylvania, USA.}, journal = {Medical cannabis and cannabinoids}, volume = {7}, number = {1}, pages = {34-43}, pmid = {38487377}, issn = {2504-3889}, abstract = {INTRODUCTION: Pennsylvania opened its first medical marijuana (MMJ) dispensary in 2018. Qualifying conditions include six conditions determined to have no or insufficient evidence to support or refute MMJ effectiveness. We conducted a study to describe MMJ dispensary access in Pennsylvania and to determine whether dispensary proximity was associated with MMJ certifications and community demographics.

METHODS: Using data from the Pennsylvania Department of Health, we geocoded MMJ dispensary locations and linked them to US Census Bureau data. We created dispensary access measures from the population-weighted centroid of Zip Code Tabulation Areas (ZCTAs): distance to nearest dispensary and density of dispensaries within a 15-min drive. We evaluated associations between dispensary access and the proportion of adults who received MMJ certification and the proportion of certifications for low evidence conditions (amyotrophic lateral sclerosis, epilepsy, glaucoma, Huntington's disease, opioid use disorder, and Parkinson's disease) using negative binomial modeling, adjusting for community features. To evaluate associations racial and ethnic composition of communities and distance to nearest dispensary, we used logistic regression to estimate the odds ratios (OR) and 95% confidence intervals (CI), adjusting for median income.

RESULTS: Distance and density of MMJ dispensaries were associated with the proportion of the ZCTA population certified and the proportion of certifications for insufficient evidence conditions. Compared to ZCTAs with no dispensary within 15 min, the proportion of adults certified increased by up to 31% and the proportion of certifications for insufficient evidence decreased by up to 22% for ZCTAs with two dispensaries. From 2018 to 2021, the odds of being within five miles of a dispensary was up to 20 times higher in ZCTAs with the highest proportions of individuals who were not White (2019: OR: 20.14, CI: 10.7-37.8) and more than double in ZCTAs with the highest proportion of Hispanic individuals (2018: OR: 2.81, CI: 1.51-5.24), compared to ZCTAs with the lowest proportions.

CONCLUSIONS: Greater dispensary access was associated with the proportions of certified residents and certifications for low evidence conditions. Whether these patterns are due to differences in accessibility or demand is unknown. Associations between community demographics and dispensary proximity may indicate MMJ access differences.}, } @article {pmid38484224, year = {2024}, author = {Sun, Y and Pahwa, S and Vasireddy, RP and Barty, A and Raslau, FD}, title = {Pearls & Oy-sters: Bibrachial Amyotrophy From a Dural Tear.}, journal = {Neurology}, volume = {102}, number = {7}, pages = {e209256}, doi = {10.1212/WNL.0000000000209256}, pmid = {38484224}, issn = {1526-632X}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis ; *Spinal Cord Diseases ; *Intracranial Hypotension ; Magnetic Resonance Imaging ; Neck ; }, abstract = {Bibrachial amyotrophy signifies a clinical phenotype characterized by weakness in both upper extremities with preserved strength in the face, neck, and lower extremities. The underlying causes of bibrachial amyotrophy are broad. We report a patient exhibiting bibrachial amyotrophy who initially received a diagnosis of amyotrophic lateral sclerosis (ALS); however, his clinical course and NCS/EMG were atypical for ALS. Further evaluation demonstrated dural tears with CSF leak, resulting in a compressive extradural fluid collection, ventral myelopathy, and intracranial hypotension. Dural tear and ALS have overlapping features, including the manifestation of the bibrachial amyotrophy phenotype and the presence of T2 hyperintensities in the anterior horn cells, recognized by an "owl's eye" appearance on spine MRI. Clinical and radiologic vigilance is required to identify rare cases of dural tear causing ventral myelopathy that manifest as bibrachial amyotrophy.}, } @article {pmid38483631, year = {2024}, author = {Perera, A and Brock, O and Ahmed, A and Shaw, C and Ashkan, K}, title = {Taking the knife to neurodegeneration: a review of surgical gene therapy delivery to the CNS.}, journal = {Acta neurochirurgica}, volume = {166}, number = {1}, pages = {136}, pmid = {38483631}, issn = {0942-0940}, mesh = {Humans ; *Central Nervous System ; Genetic Therapy/methods ; Genetic Vectors ; *Neurodegenerative Diseases/genetics/therapy ; }, abstract = {Gene supplementation and editing for neurodegenerative disorders has emerged in recent years as the understanding of the genetic mechanisms underlying several neurodegenerative disorders increases. The most common medium to deliver genetic material to cells is via viral vectors; and with respect to the central nervous system, adeno-associated viral (AAV) vectors are a popular choice. The most successful example of AAV-based gene therapy for neurodegenerative disorders is Zolgensma© which is a transformative intravenous therapy given to babies with spinal muscular atrophy. However, the field has stalled in achieving safe drug delivery to the central nervous system in adults for which treatments for disorders such as amyotrophic lateral sclerosis are desperately needed. Surgical gene therapy delivery has been proposed as a potential solution to this problem. While the field of the so-called regenerative neurosurgery has yielded pre-clinical optimism, several challenges have emerged. This review seeks to explore the field of regenerative neurosurgery with respect to AAV-based gene therapy for neurodegenerative diseases, its progress so far and the challenges that need to be overcome.}, } @article {pmid38483313, year = {2024}, author = {Jafarinia, H and van der Giessen, E and Onck, PR}, title = {C9orf72 polyPR directly binds to various nuclear transport components.}, journal = {eLife}, volume = {12}, number = {}, pages = {}, pmid = {38483313}, issn = {2050-084X}, support = {Building Blocks of Life//Nederlandse Organisatie voor Wetenschappelijk Onderzoek/ ; }, mesh = {Active Transport, Cell Nucleus ; C9orf72 Protein/genetics ; *Nuclear Localization Signals ; *Amino Acids ; Arginine ; }, abstract = {The disruption of nucleocytoplasmic transport (NCT) is an important mechanism in neurodegenerative diseases. In the case of C9orf72-ALS, trafficking of macromolecules through the nuclear pore complex (NPC) might get frustrated by the binding of C9orf72-translated arginine-containing dipeptide repeat proteins (R-DPRs) to the Kapβ family of nuclear transport receptors. Besides Kapβs, several other types of transport components have been linked to NCT impairments in R-DPR-expressed cells, but the molecular origin of these observations has not been clarified. Here, we adopt a coarse-grained molecular dynamics model at amino acid resolution to study the direct interaction between polyPR, the most toxic DPR, and various nuclear transport components to elucidate the binding mechanisms and provide a complete picture of potential polyPR-mediated NCT defects. We found polyPR to directly bind to several isoforms of the Impα family, CAS (the specific exporter of Impα) and RanGAP. We observe no binding between polyPR and Ran. Longer polyPRs at lower salt concentrations also make contact with RanGEF and NTF2. Analyzing the polyPR contact sites on the transport components reveals that polyPR potentially interferes with RanGTP/RanGDP binding, with nuclear localization signal (NLS)-containing cargoes (cargo-NLS) binding to Impα, with cargo-NLS release from Impα, and with Impα export from the nucleus. The abundance of polyPR-binding sites on multiple transport components combined with the inherent polyPR length dependence makes direct polyPR interference of NCT a potential mechanistic pathway of C9orf72 toxicity.}, } @article {pmid38483107, year = {2024}, author = {Adari, MD and Pandian, BA and Gaines, TA and Prasad, PV and Jugulam, M}, title = {Confirmation and characterization of the first case of acetolactate synthase (ALS)-inhibitor resistance in Japanese brome (Bromus japonicus) in the US.}, journal = {Pest management science}, volume = {80}, number = {8}, pages = {3717-3725}, doi = {10.1002/ps.8074}, pmid = {38483107}, issn = {1526-4998}, mesh = {*Acetolactate Synthase/genetics/antagonists & inhibitors/metabolism ; *Bromus/enzymology/drug effects/genetics ; *Herbicide Resistance/genetics ; *Herbicides/pharmacology ; Kansas ; *Plant Proteins/genetics/metabolism/antagonists & inhibitors ; Plant Weeds/drug effects/genetics/enzymology ; }, abstract = {BACKGROUND: Japanese brome (Bromus japonicus Thumb.) is one of the problematic annual weeds in winter wheat (Triticum aestivum L.) and is generally controlled by acetolactate synthase (ALS) inhibitors. Repeated use of the ALS inhibitor propoxycarbazone-Na resulted in the evolution of resistance to this herbicide in three B. japonicus populations, i.e., R1, R2, and R3 in Kansas (KS). However, the level of resistance and mechanism conferring resistance in these populations is unknown. The objectives of this research were to (i) evaluate the level of resistance to propoxycarbazone-Na in R1, R2, and R3 in comparison with a known susceptible population (S1), (ii) investigate the mechanism of resistance involved in conferring ALS-inhibitor resistance, and (iii) investigate the cross-resistance to other ALS inhibitors.

RESULTS: Dose-response (0 to 16x; x = 44 g ai ha[-1] of propoxycarbazone-Na) assay indicated 167, 125, and 667-fold resistance in R1, R2 and R3 populations, respectively, compared to S1 population. ALS gene sequencing confirmed the mutations resulting in amino acid substitutions, i.e., Pro-197-Thr (R3, R1)/Ser (R2, R1) bestowing resistance to these ALS inhibitors. Such amino acid substitutions also showed differential cross-resistance to sulfosulfuron, mesosulfuron-methyl, pyroxsulam, and imazamox among resistant populations. Pretreatment with malathion (a cytochrome P450 enzyme-inhibitor) followed by imazamox treatment suggested cross-resistance to this herbicide possibly via metabolism only in R3 population.

CONCLUSION: Overall, these results confirm the first case of target-site based resistance to ALS inhibitors in B. japonicus in the US, highlighting the need for exploring herbicides with alternative modes of action to enhance weed control in winter wheat. © 2024 Society of Chemical Industry.}, } @article {pmid38481899, year = {2024}, author = {El-Ghanem, M and Abdulrazeq, H and Brasiliense, L and Abbad, H and Aguilar-Salinas, P and Al-Mufti, F and Dumont, T}, title = {Outcomes of Mechanical Thrombectomy in Patients With Neurological Disorders: A National Inpatient Sample Database Analysis.}, journal = {Cureus}, volume = {16}, number = {2}, pages = {e54063}, pmid = {38481899}, issn = {2168-8184}, abstract = {INTRODUCTION: Mechanical thrombectomy (MT) has changed the standard of care for patients presenting with acute ischemic stroke (AIS). The window of treatment has significantly increased the number of patients who would benefit from intervention and operators may be confronted with patients harboring preexistent neurological disorders. Still, the epidemiology of patients with AIS and neurological disorders has not been established.

METHODS: This is a retrospective study, which utilizes data from the National Inpatient Sample (NIS) between 2012 and 2016. Patients with the major neurological comorbidities in the study were included: Alzheimer's dementia (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), and myasthenia gravis (MG). These patients were divided into groups and analyzed based on discharged home status, length of hospital stay (LOS), and inpatient mortality. These outcomes were also compared between patients who underwent MT versus those who did not.

RESULTS: In this study, 460,070 patients with AIS were identified and included. MT was performed less often when the patient had a neurological diagnosis compared to those without a neurological disease (p<0.0001). However, patients with AIS who have underlying neurological disorders such as AD, PD, and MS have shown similar outcomes after MT to those who do not have these disorders.

CONCLUSION: Patients with preexisting neurological disorders were less likely to undergo MT. Further studies are required to elucidate the implications of having a neurological disorder in the setting of an AIS.}, } @article {pmid38481294, year = {2024}, author = {Laforest, M and Martin, SL and Bisaillon, K and Soufiane, B and Meloche, S and Tardif, FJ and Page, E}, title = {The ancestral karyotype of the Heliantheae Alliance, herbicide resistance, and human allergens: Insights from the genomes of common and giant ragweed.}, journal = {The plant genome}, volume = {17}, number = {2}, pages = {e20442}, doi = {10.1002/tpg2.20442}, pmid = {38481294}, issn = {1940-3372}, support = {J-001751//Agriculture and Agri-Food Canada/ ; J-002275//Agriculture and Agri-Food Canada/ ; }, mesh = {*Ambrosia/genetics ; *Allergens/genetics ; *Herbicide Resistance/genetics ; *Genome, Plant ; Humans ; Karyotype ; Herbicides/pharmacology ; Chromosomes, Plant ; }, abstract = {Ambrosia artemisiifolia and Ambrosia trifida (Asteraceae) are important pest species and the two greatest sources of aeroallergens globally. Here, we took advantage of a hybrid to simplify genome assembly and present chromosome-level assemblies for both species. These assemblies show high levels of completeness with Benchmarking Universal Single-Copy Ortholog (BUSCO) scores of 94.5% for A. artemisiifolia and 96.1% for A. trifida and long terminal repeat (LTR) Assembly Index values of 26.6 and 23.6, respectively. The genomes were annotated using RNA data identifying 41,642 genes in A. artemisiifolia and 50,203 in A. trifida. More than half of the genome is composed of repetitive elements, with 62% in A. artemisiifolia and 69% in A. trifida. Single copies of herbicide resistance-associated genes PPX2L, HPPD, and ALS were found, while two copies of the EPSPS gene were identified; this latter observation may reveal a possible mechanism of resistance to the herbicide glyphosate. Ten of the 12 main allergenicity genes were also localized, some forming clusters with several copies, especially in A. artemisiifolia. The evolution of genome structure has differed among these two species. The genome of A. trifida has undergone greater rearrangement, possibly the result of chromoplexy. In contrast, the genome of A. artemisiifolia retains a structure that makes the allotetraploidization of the most recent common ancestor of the Heliantheae Alliance the clearest feature of its genome. When compared to other Heliantheae Alliance species, this allowed us to reconstruct the common ancestor's karyotype-a key step for furthering of our understanding of the evolution and diversification of this economically and allergenically important group.}, } @article {pmid38479182, year = {2024}, author = {Nie, L and He, K and Qiu, C and Li, Q and Xiong, B and Gao, C and Zhang, X and Jing, M and Wu, W and Liu, J and Zhang, G and Zhang, Z and Yang, X and Sun, Y and Wang, Y}, title = {Tetramethylpyrazine Nitrone alleviates D-galactose-induced murine skeletal muscle aging and motor deficits by activating the AMPK signaling pathway.}, journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie}, volume = {173}, number = {}, pages = {116415}, doi = {10.1016/j.biopha.2024.116415}, pmid = {38479182}, issn = {1950-6007}, mesh = {Mice ; Animals ; *Galactose ; AMP-Activated Protein Kinases ; *Neuroprotective Agents/pharmacology ; Aging ; Signal Transduction ; Muscle, Skeletal ; *Pyrazines ; }, abstract = {Tetramethylpyrazine nitrone (TBN), a novel derivative of tetramethylpyrazine (TMP) designed and synthesized by our group, possesses multi-functional mechanisms of action and displays broad protective effects in vitro and in animal models of age-related brain disorders such as stroke, Alzheimer's disease (AD), Amyotrophic Lateral Sclerosis (ALS) and Parkinson's disease (PD). In the present report, we investigated the effects of TBN on aging, specifically on muscle aging and the associated decline of motor functions. Using a D-galactose-induced aging mouse model, we found that TBN could reverse the levels of several senescence and aging markers including p16, p21, ceramides, and telomere length and increase the wet-weight ratio of gastrocnemius muscle tissue, demonstrating its efficacy in ameliorating muscle aging. Additionally, the pharmacological effects of TBN on motor deficits (gait analysis, pole-climbing test and grip strength test), muscle fibrosis (hematoxylin & eosin (HE), Masson staining, and αSMA staining), inflammatory response (IL-1β, IL-6, and TNF-α), and mitochondrial function (ATP, mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) were also confirmed in the D-galactose-induced aging models. Further experiments demonstrated that TBN alleviated muscle aging and improved the decline of age-related motor deficits through an AMPK-dependent mechanism. These findings highlight the significance of TBN as a potential anti-aging agent to combat the occurrence and development of aging and age-related diseases.}, } @article {pmid38478631, year = {2024}, author = {Scekic-Zahirovic, J and Benetton, C and Brunet, A and Ye, X and Logunov, E and Douchamps, V and Megat, S and Andry, V and Kan, VWY and Stuart-Lopez, G and Gilet, J and Guillot, SJ and Dirrig-Grosch, S and Gorin, C and Trombini, M and Dieterle, S and Sinniger, J and Fischer, M and René, F and Gunes, Z and Kessler, P and Dupuis, L and Pradat, PF and Goumon, Y and Goutagny, R and Marchand-Pauvert, V and Liebscher, S and Rouaux, C}, title = {Cortical hyperexcitability in mouse models and patients with amyotrophic lateral sclerosis is linked to noradrenaline deficiency.}, journal = {Science translational medicine}, volume = {16}, number = {738}, pages = {eadg3665}, doi = {10.1126/scitranslmed.adg3665}, pmid = {38478631}, issn = {1946-6242}, mesh = {Humans ; Mice ; Animals ; *Amyotrophic Lateral Sclerosis/metabolism ; Superoxide Dismutase-1/genetics/metabolism ; *Neurodegenerative Diseases/metabolism ; Spinal Cord/metabolism ; Norepinephrine/*deficiency ; Disease Models, Animal ; Mice, Transgenic ; Superoxide Dismutase/metabolism ; *Autonomic Nervous System Diseases ; Dopamine beta-Hydroxylase/*deficiency ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease, characterized by the death of upper (UMN) and lower motor neurons (LMN) in the motor cortex, brainstem, and spinal cord. Despite decades of research, ALS remains incurable, challenging to diagnose, and of extremely rapid progression. A unifying feature of sporadic and familial forms of ALS is cortical hyperexcitability, which precedes symptom onset, negatively correlates with survival, and is sufficient to trigger neurodegeneration in rodents. Using electrocorticography in the Sod1[G86R] and Fus[ΔNLS/+] ALS mouse models and standard electroencephalography recordings in patients with sporadic ALS, we demonstrate a deficit in theta-gamma phase-amplitude coupling (PAC) in ALS. In mice, PAC deficits started before symptom onset, and in patients, PAC deficits correlated with the rate of disease progression. Using mass spectrometry analyses of CNS neuropeptides, we identified a presymptomatic reduction of noradrenaline (NA) in the motor cortex of ALS mouse models, further validated by in vivo two-photon imaging in behaving SOD1[G93A] and Fus[ΔNLS/+] mice, that revealed pronounced reduction of locomotion-associated NA release. NA deficits were also detected in postmortem tissues from patients with ALS, along with transcriptomic alterations of noradrenergic signaling pathways. Pharmacological ablation of noradrenergic neurons with DSP-4 reduced theta-gamma PAC in wild-type mice and administration of a synthetic precursor of NA augmented theta-gamma PAC in ALS mice. Our findings suggest theta-gamma PAC as means to assess and monitor cortical dysfunction in ALS and warrant further investigation of the NA system as a potential therapeutic target.}, } @article {pmid38478117, year = {2024}, author = {Marques, C and Held, A and Dorfman, K and Sung, J and Song, C and Kavuturu, AS and Aguilar, C and Russo, T and Oakley, DH and Albers, MW and Hyman, BT and Petrucelli, L and Lagier-Tourenne, C and Wainger, BJ}, title = {Neuronal STING activation in amyotrophic lateral sclerosis and frontotemporal dementia.}, journal = {Acta neuropathologica}, volume = {147}, number = {1}, pages = {56}, pmid = {38478117}, issn = {1432-0533}, support = {RF1 NS127407/NS/NINDS NIH HHS/United States ; DP2 NS106664/NS/NINDS NIH HHS/United States ; I01 BX002466/BX/BLRD VA/United States ; RF1NS127407/NH/NIH HHS/United States ; DP2-NS106664/NH/NIH HHS/United States ; F32 NS114319/NS/NINDS NIH HHS/United States ; P30 AG062421/AG/NIA NIH HHS/United States ; F32NS114319/NH/NIH HHS/United States ; }, mesh = {Animals ; Humans ; Mice ; *Amyotrophic Lateral Sclerosis/genetics/metabolism ; C9orf72 Protein/genetics ; *Frontotemporal Dementia/genetics/metabolism ; *Induced Pluripotent Stem Cells/metabolism ; Motor Neurons/metabolism ; *Pick Disease of the Brain ; }, abstract = {The stimulator of interferon genes (STING) pathway has been implicated in neurodegenerative diseases, including Parkinson's disease and amyotrophic lateral sclerosis (ALS). While prior studies have focused on STING within immune cells, little is known about STING within neurons. Here, we document neuronal activation of the STING pathway in human postmortem cortical and spinal motor neurons from individuals affected by familial or sporadic ALS. This process takes place selectively in the most vulnerable cortical and spinal motor neurons but not in neurons that are less affected by the disease. Concordant STING activation in layer V cortical motor neurons occurs in a mouse model of C9orf72 repeat-associated ALS and frontotemporal dementia (FTD). To establish that STING activation occurs in a neuron-autonomous manner, we demonstrate the integrity of the STING signaling pathway, including both upstream activators and downstream innate immune response effectors, in dissociated mouse cortical neurons and neurons derived from control human induced pluripotent stem cells (iPSCs). Human iPSC-derived neurons harboring different familial ALS-causing mutations exhibit increased STING signaling with DNA damage as a main driver. The elevated downstream inflammatory markers present in ALS iPSC-derived neurons can be suppressed with a STING inhibitor. Our results reveal an immunophenotype that consists of innate immune signaling driven by the STING pathway and occurs specifically within vulnerable neurons in ALS/FTD.}, } @article {pmid38477424, year = {2025}, author = {Steigerwald, CG and Bertolini, C and McElhiney, M and Bergner, AL and Harms, MB and Harrington, EA}, title = {Individuals' experiences in genetic counseling and predictive testing for familial amyotrophic lateral sclerosis.}, journal = {Journal of genetic counseling}, volume = {34}, number = {1}, pages = {e1890}, doi = {10.1002/jgc4.1890}, pmid = {38477424}, issn = {1573-3599}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/psychology/diagnosis ; *Genetic Counseling/psychology ; *Genetic Testing ; Male ; Female ; Middle Aged ; Adult ; Surveys and Questionnaires ; Aged ; }, abstract = {As clinical genetic testing in the amyotrophic lateral sclerosis (ALS) diagnostic setting increases, the identification of at-risk family members has also expanded. No practice guidelines specifically for predictive genetic testing exist, and few studies about the psychological impacts of testing in this subgroup have occurred, limiting the ability to tailor recommendations and counseling in this community. We surveyed asymptomatic individuals at risk for inheriting an ALS-associated gene mutation. The 80-question survey was designed using a combination of validated measures (General Anxiety Disorder; FACToR; Decision Regret Scale) and original items. Ninety participants completed the survey, including those who completed predictive genetic testing (N = 42) and those who did not (N = 48). Gene positive individuals experienced greater negativity, uncertainty, and overall psychological impairment (p = 0.002; p < 0.001; p = 0.001). Individuals who had not undergone testing reported thinking about their risk multiple times per day and experiencing more decisional regret than those who tested (p = 0.006). In terms of decision-making, being prepared for potential clinical drug trials was a more important potential benefit among those who underwent testing (p = 0.026). Participants valuing preparedness for clinical drug trials supports the concept that genetic testing for ALS will increase as research in gene-targeted therapeutics progresses. This study describes factors relevant to the genetic testing decision-making process and adaptation to results from the perspective of at-risk individuals, which can ultimately guide genetic counseling practice in this population.}, } @article {pmid38477419, year = {2024}, author = {de Fátima Dos Santos Sampaio, M and de Paiva, YB and Sampaio, TB and Pereira, MG and Coimbra, NC}, title = {Therapeutic applicability of cannabidiol and other phytocannabinoids in epilepsy, multiple sclerosis and Parkinson's disease and in comorbidity with psychiatric disorders.}, journal = {Basic & clinical pharmacology & toxicology}, volume = {134}, number = {5}, pages = {574-601}, doi = {10.1111/bcpt.13997}, pmid = {38477419}, issn = {1742-7843}, support = {2014/11869-0//Fundação de Amparo à Pesquisa do Estado de São Paulo/ ; 2020/15050-7//Fundação de Amparo à Pesquisa do Estado de São Paulo/ ; PDJ grant 155489/2018-6//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; Research Grant (NAP-USP-NuPNE; process IaPq2012-15//Universidade de São Paulo/ ; 374/2022//Fundação de Apoio ao Ensino, Pesquisa e Assistência do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo/ ; 302605/2021-5//CNPq/ ; 301341/2015-0//CNPq/ ; 301905/2010-0//CNPq/ ; 155489/2018-6//CNPq/ ; }, mesh = {Humans ; *Cannabidiol/pharmacology/therapeutic use ; *Parkinson Disease/drug therapy ; *Multiple Sclerosis/drug therapy ; Receptor, Serotonin, 5-HT1A/therapeutic use ; *Cannabinoids/pharmacology/therapeutic use ; *Epilepsy/drug therapy ; *Mental Disorders/drug therapy ; Comorbidity ; }, abstract = {Studies have demonstrated the neuroprotective effect of cannabidiol (CBD) and other Cannabis sativa L. derivatives on diseases of the central nervous system caused by their direct or indirect interaction with endocannabinoid system-related receptors and other molecular targets, such as the 5-HT1A receptor, which is a potential pharmacological target of CBD. Interestingly, CBD binding with the 5-HT1A receptor may be suitable for the treatment of epilepsies, parkinsonian syndromes and amyotrophic lateral sclerosis, in which the 5-HT1A serotonergic receptor plays a key role. The aim of this review was to provide an overview of cannabinoid effects on neurological disorders, such as epilepsy, multiple sclerosis and Parkinson's diseases, and discuss their possible mechanism of action, highlighting interactions with molecular targets and the potential neuroprotective effects of phytocannabinoids. CBD has been shown to have significant therapeutic effects on epilepsy and Parkinson's disease, while nabiximols contribute to a reduction in spasticity and are a frequent option for the treatment of multiple sclerosis. Although there are multiple theories on the therapeutic potential of cannabinoids for neurological disorders, substantially greater progress in the search for strong scientific evidence of their pharmacological effectiveness is needed.}, } @article {pmid38474719, year = {2024}, author = {Noor Eddin, A and Alfuwais, M and Noor Eddin, R and Alkattan, K and Yaqinuddin, A}, title = {Gut-Modulating Agents and Amyotrophic Lateral Sclerosis: Current Evidence and Future Perspectives.}, journal = {Nutrients}, volume = {16}, number = {5}, pages = {}, pmid = {38474719}, issn = {2072-6643}, mesh = {Animals ; Humans ; *Amyotrophic Lateral Sclerosis/pathology ; Dysbiosis/etiology ; *Gastrointestinal Microbiome/physiology ; *Microbiota ; Disease Progression ; }, abstract = {Amyotrophic Lateral Sclerosis (ALS) is a highly fatal neurodegenerative disorder characterized by the progressive wasting and paralysis of voluntary muscle. Despite extensive research, the etiology of ALS remains elusive, and effective treatment options are limited. However, recent evidence implicates gut dysbiosis and gut-brain axis (GBA) dysfunction in ALS pathogenesis. Alterations to the composition and diversity of microbial communities within the gut flora have been consistently observed in ALS patients. These changes are often correlated with disease progression and patient outcome, suggesting that GBA modulation may have therapeutic potential. Indeed, targeting the gut microbiota has been shown to be neuroprotective in several animal models, alleviating motor symptoms and mitigating disease progression. However, the translation of these findings to human patients is challenging due to the complexity of ALS pathology and the varying diversity of gut microbiota. This review comprehensively summarizes the current literature on ALS-related gut dysbiosis, focusing on the implications of GBA dysfunction. It delineates three main mechanisms by which dysbiosis contributes to ALS pathology: compromised intestinal barrier integrity, metabolic dysfunction, and immune dysregulation. It also examines preclinical evidence on the therapeutic potential of gut-microbiota-modulating agents (categorized as prebiotics, probiotics, and postbiotics) in ALS.}, } @article {pmid38474416, year = {2024}, author = {Tzeplaeff, L and Jürs, AV and Wohnrade, C and Demleitner, AF}, title = {Unraveling the Heterogeneity of ALS-A Call to Redefine Patient Stratification for Better Outcomes in Clinical Trials.}, journal = {Cells}, volume = {13}, number = {5}, pages = {}, pmid = {38474416}, issn = {2073-4409}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/pathology ; Treatment Outcome ; Clinical Trials as Topic ; }, abstract = {Despite tremendous efforts in basic research and a growing number of clinical trials aiming to find effective treatments, amyotrophic lateral sclerosis (ALS) remains an incurable disease. One possible reason for the lack of effective causative treatment options is that ALS may not be a single disease entity but rather may represent a clinical syndrome, with diverse genetic and molecular causes, histopathological alterations, and subsequent clinical presentations contributing to its complexity and variability among individuals. Defining a way to subcluster ALS patients is becoming a central endeavor in the field. Identifying specific clusters and applying them in clinical trials could enable the development of more effective treatments. This review aims to summarize the available data on heterogeneity in ALS with regard to various aspects, e.g., clinical, genetic, and molecular.}, } @article {pmid38474399, year = {2024}, author = {Manora, L and Borlongan, CV and Garbuzova-Davis, S}, title = {Cellular and Noncellular Approaches for Repairing the Damaged Blood-CNS-Barrier in Amyotrophic Lateral Sclerosis.}, journal = {Cells}, volume = {13}, number = {5}, pages = {}, pmid = {38474399}, issn = {2073-4409}, support = {R01 NS090962/NS/NINDS NIH HHS/United States ; R21 NS132576/NS/NINDS NIH HHS/United States ; 1R21NS132576-01/NS/NINDS NIH HHS/United States ; 1R01NS090962/NS/NINDS NIH HHS/United States ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism ; Endothelial Cells/metabolism ; *Neurodegenerative Diseases/metabolism ; Motor Neurons/metabolism ; Stem Cells/metabolism ; }, abstract = {Numerous reports have demonstrated the breakdown of the blood-CNS barrier (B-CNS-B) in amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease. Re-establishing barrier integrity in the CNS is critical to prevent further motor neuron degeneration from harmful components in systemic circulation. Potential therapeutic strategies for repairing the B-CNS-B may be achieved by the replacement of damaged endothelial cells (ECs) via stem cell administration or enhancement of endogenous EC survival through the delivery of bioactive particles secreted by stem cells. These cellular and noncellular approaches are thoroughly discussed in the present review. Specific attention is given to certain stem cell types for EC replacement. Also, various nanoparticles secreted by stem cells as well as other biomolecules are elucidated as promising agents for endogenous EC repair. Although the noted in vitro and in vivo studies show the feasibility of the proposed therapeutic approaches to the repair of the B-CNS-B in ALS, further investigation is needed prior to clinical transition.}, } @article {pmid38474336, year = {2024}, author = {Aksoy, YA and Cole, AJ and Deng, W and Hesselson, D}, title = {Zebrafish CCNF and FUS Mediate Stress-Specific Motor Responses.}, journal = {Cells}, volume = {13}, number = {5}, pages = {}, pmid = {38474336}, issn = {2073-4409}, support = {APP1095215//NHMRC/ ; APP1063981//NHMRC/ ; DP140103233/ARC/Ames Research Center NASA/United States ; }, mesh = {Animals ; Humans ; *Amyotrophic Lateral Sclerosis/metabolism ; *Cyclins/metabolism ; Motor Neurons/pathology ; *Neurodegenerative Diseases/metabolism ; Proteins/metabolism ; *RNA-Binding Protein FUS/genetics/metabolism ; *Zebrafish/metabolism ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by the degeneration of motor neurons. Mutations in the cyclin F (CCNF) and fused in sarcoma (FUS) genes have been associated with ALS pathology. In this study, we aimed to investigate the functional role of CCNF and FUS in ALS by using genome editing techniques to generate zebrafish models with genetic disruptions in these genes. Sequence comparisons showed significant homology between human and zebrafish CCNF and FUS proteins. We used CRISPR/Cas9 and TALEN-mediated genome editing to generate targeted disruptions in the zebrafish ccnf and fus genes. Ccnf-deficient zebrafish exhibited abnormal motor neuron development and axonal outgrowth, whereas Fus-deficient zebrafish did not exhibit developmental abnormalities or axonopathies in primary motor neurons. However, Fus-deficient zebrafish displayed motor impairments in response to oxidative and endoplasmic reticulum stress. The Ccnf-deficient zebrafish were only sensitized to endoplasmic reticulum stress, indicating that ALS genes have overlapping as well as unique cellular functions. These zebrafish models provide valuable platforms for studying the functional consequences of CCNF and FUS mutations in ALS pathogenesis. Furthermore, these zebrafish models expand the drug screening toolkit used to evaluate possible ALS treatments.}, } @article {pmid38474192, year = {2024}, author = {Yamashita, T and Abe, K}, title = {Update on Antioxidant Therapy with Edaravone: Expanding Applications in Neurodegenerative Diseases.}, journal = {International journal of molecular sciences}, volume = {25}, number = {5}, pages = {}, pmid = {38474192}, issn = {1422-0067}, support = {23K08543, 21K19572//Grant-in-Aid for Scientific Research/ ; }, mesh = {Animals ; Female ; Pregnancy ; *Amyotrophic Lateral Sclerosis/drug therapy ; Antioxidants/therapeutic use ; Antipyrine ; Edaravone/pharmacology/therapeutic use ; Free Radical Scavengers/pharmacology ; *Neurodegenerative Diseases/drug therapy ; *Neuroprotective Agents/pharmacology ; Placenta ; }, abstract = {The brain is susceptible to oxidative stress, which is associated with various neurological diseases. Edaravone (MCI-186, 3-methyl-1 pheny-2-pyrazolin-5-one), a free radical scavenger, has promising effects by quenching hydroxyl radicals (∙OH) and inhibiting both ∙OH-dependent and ∙OH-independent lipid peroxidation. Edaravone was initially developed in Japan as a neuroprotective agent for acute cerebral infarction and was later applied clinically to treat amyotrophic lateral sclerosis (ALS), a neurodegenerative disease. There is accumulating evidence for the therapeutic effects of edaravone in a wide range of diseases related to oxidative stress, including ischemic stroke, ALS, Alzheimer's disease, and placental ischemia. These neuroprotective effects have expanded the potential applications of edaravone. Data from experimental animal models support its safety for long-term use, implying broader applications in various neurodegenerative diseases. In this review, we explain the unique characteristics of edaravone, summarize recent findings for specific diseases, and discuss its prospects for future therapeutic applications.}, } @article {pmid38473944, year = {2024}, author = {Scarian, E and Viola, C and Dragoni, F and Di Gerlando, R and Rizzo, B and Diamanti, L and Gagliardi, S and Bordoni, M and Pansarasa, O}, title = {New Insights into Oxidative Stress and Inflammatory Response in Neurodegenerative Diseases.}, journal = {International journal of molecular sciences}, volume = {25}, number = {5}, pages = {}, pmid = {38473944}, issn = {1422-0067}, support = {Ricerca Corrente 2022-2024//Ministero della Salute/ ; }, mesh = {Humans ; *Neurodegenerative Diseases/metabolism ; Oxidative Stress/physiology ; Antioxidants/metabolism ; *Amyotrophic Lateral Sclerosis/metabolism ; Inflammation/drug therapy ; }, abstract = {Oxidative stress (OS) and inflammation are two important and well-studied pathological hallmarks of neurodegenerative diseases (NDDs). Due to elevated oxygen consumption, the high presence of easily oxidizable polyunsaturated fatty acids and the weak antioxidant defenses, the brain is particularly vulnerable to oxidative injury. Uncertainty exists over whether these deficits contribute to the development of NDDs or are solely a consequence of neuronal degeneration. Furthermore, these two pathological hallmarks are linked, and it is known that OS can affect the inflammatory response. In this review, we will overview the last findings about these two pathways in the principal NDDs. Moreover, we will focus more in depth on amyotrophic lateral sclerosis (ALS) to understand how anti-inflammatory and antioxidants drugs have been used for the treatment of this still incurable motor neuron (MN) disease. Finally, we will analyze the principal past and actual clinical trials and the future perspectives in the study of these two pathological mechanisms.}, } @article {pmid38472280, year = {2024}, author = {Safren, N and Dao, TP and Mohan, HM and Huang, C and Trotter, B and Castañeda, CA and Paulson, H and Barmada, S and Sharkey, LM}, title = {Pathogenic mutations in UBQLN2 exhibit diverse aggregation propensity and neurotoxicity.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {6049}, pmid = {38472280}, issn = {2045-2322}, support = {R01 GM136946/GM/NIGMS NIH HHS/United States ; R01GM136946./GF/NIH HHS/United States ; R01NS097542-01/GF/NIH HHS/United States ; R35 NS122302/NS/NINDS NIH HHS/United States ; R35NS122302/GF/NIH HHS/United States ; }, mesh = {Humans ; *Frontotemporal Dementia/genetics ; *Amyotrophic Lateral Sclerosis/metabolism ; Autophagy-Related Proteins/genetics ; Mutation ; Adaptor Proteins, Signal Transducing/metabolism ; }, abstract = {The ubiquitin-adaptor protein UBQLN2 promotes degradation of several aggregate-prone proteins implicated in neurodegenerative diseases. Missense UBQLN2 mutations also cause X-linked amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Previously we demonstrated that the liquid-like properties of UBQLN2 molecular assemblies are altered by a specific pathogenic mutation, P506T, and that the propensity of UBQLN2 to aggregate correlated with neurotoxicity. Here, we systematically assess the effects of multiple, spatially distinct ALS/FTD-linked missense mutations on UBQLN2 aggregation propensity, neurotoxicity, phase separation, and autophagic flux. In contrast to what we observed for the P506T mutation, no other tested pathogenic mutant exhibited a clear correlation between aggregation propensity and neurotoxicity. These results emphasize the unique nature of pathogenic UBQLN2 mutations and argue against a generalizable link between aggregation propensity and neurodegeneration in UBQLN2-linked ALS/FTD.}, } @article {pmid38472048, year = {2024}, author = {Silva-Hucha, S and Fernández de Sevilla, ME and Humphreys, KM and Benson, FE and Franco, JM and Pozo, D and Pastor, AM and Morcuende, S}, title = {VEGF expression disparities in brainstem motor neurons of the SOD1[G93A] ALS model: Correlations with neuronal vulnerability.}, journal = {Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics}, volume = {21}, number = {3}, pages = {e00340}, pmid = {38472048}, issn = {1878-7479}, mesh = {Animals ; Humans ; Mice ; *Amyotrophic Lateral Sclerosis/metabolism/genetics ; *Brain Stem/metabolism ; Disease Models, Animal ; Mice, Transgenic ; *Motor Neurons/metabolism/pathology ; Superoxide Dismutase/metabolism/genetics ; *Superoxide Dismutase-1/genetics/metabolism ; *Vascular Endothelial Growth Factor A/metabolism/genetics ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a rare neuromuscular disease characterized by severe muscle weakness mainly due to degeneration and death of motor neurons. A peculiarity of the neurodegenerative processes is the variable susceptibility among distinct neuronal populations, exemplified by the contrasting resilience of motor neurons innervating the ocular motor system and the more vulnerable facial and hypoglossal motor neurons. The crucial role of vascular endothelial growth factor (VEGF) as a neuroprotective factor in the nervous system is well-established since a deficit of VEGF has been related to motoneuronal degeneration. In this study, we investigated the survival of ocular, facial, and hypoglossal motor neurons utilizing the murine SOD1[G93A] ALS model at various stages of the disease. Our primary objective was to determine whether the survival of the different brainstem motor neurons was linked to disparate VEGF expression levels in resilient and susceptible motor neurons throughout neurodegeneration. Our findings revealed a selective loss of motor neurons exclusively within the vulnerable nuclei. Furthermore, a significantly higher level of VEGF was detected in the more resistant motor neurons, the extraocular ones. We also examined whether TDP-43 dynamics in the brainstem motor neuron of SOD mice was altered. Our data suggests that the increased VEGF levels observed in extraocular motor neurons may potentially underlie their resistance during the neurodegenerative processes in ALS in a TDP-43-independent manner. Our work might help to better understand the underlying mechanisms of selective vulnerability of motor neurons in ALS.}, } @article {pmid38471489, year = {2024}, author = {D'Souza, A and Zink, K and Langhorst, J and Wildner, M and Stupp, C and Keil, T}, title = {How Effective Is Drinking Natural Mineral Water against Heartburn from Functional Dyspepsia, Gastroesophageal Reflux Disease, or Other Causes? A Systematic Review of Clinical Intervention Studies.}, journal = {Complementary medicine research}, volume = {31}, number = {3}, pages = {253-265}, pmid = {38471489}, issn = {2504-2106}, mesh = {Humans ; *Mineral Waters/therapeutic use ; *Gastroesophageal Reflux/therapy/drug therapy ; *Heartburn/drug therapy ; *Dyspepsia/drug therapy ; Randomized Controlled Trials as Topic ; }, abstract = {BACKGROUND: For centuries, spring and other natural waters have been recommended as external or internal remedies for numerous diseases. For studies that examined the effects of drinking mineral waters against heartburn, gastroesophageal reflux disease (GERD), or functional dyspepsia, a systematic review is lacking.

OBJECTIVES: The main aim of this systematic review was to examine the effects of drinking natural mineral waters on heartburn from various causes by identifying all published intervention studies and critically appraising their methods as well as summarizing their results.

METHODS: We systematically searched the largest medical literature database MEDLINE, further relevant web sources, and gray literature for randomized and nonrandomized trials, with or without control groups, up to September 2021 and no language restrictions. Further inclusion criteria were adult patients with heartburn, drinking cure with natural mineral water as the intervention, compared to no or other interventions (care-as-usual, waiting list). We defined the reduction of heartburn symptoms and duration of disease episodes as primary and quality of life as secondary outcomes. Two reviewers independently carried out the study quality assessments (risk of bias) using the National Institutes of Health-Study Quality Assessment Tools.

RESULTS: Nine trials comprising 393 patients from Italy, Russia, Ukraine, and Germany fulfilled all inclusion criteria. We identified three randomized controlled trials (all with poor methodological quality), plus six before-after (pre/post) intervention studies without a control group. The intervention groups of the three comparative trials seemed to show a stronger reduction of self-reported heartburn symptoms, and duration of heartburn episodes than the respective control groups; however, they all had poor methodological quality.

CONCLUSION: Based on the best available evidence of clinical studies, we cannot recommend or advise against drinking natural mineral waters as a treatment for heartburn. The potential benefits of natural mineral waters that were reported in some studies with a lower evidence level (e.g., lacking a control group) should be verified by good quality randomized clinical trials with adequate comparison groups and longer follow-up periods.

UNLABELLED: HintergrundSeit Jahrhunderten werden Quell- und andere natürliche Wässer als äußerliche oder innerliche Heilmittel für zahlreiche Krankheiten empfohlen. Für Studien, die die Wirkung des Trinkens von Mineralwasser gegen Sodbrennen, gastroösophageale Refluxkrankheit (GERD) oder funktionelle Dyspepsie untersuchten, fehlt eine systematische Übersicht.ZielsetzungDas Hauptziel dieser systematischen Übersichtsarbeit war es, die Auswirkungen von Trinkkuren mit natürlichen Mineralwässern auf Sodbrennen verschiedener Ursachen zu untersuchen, indem alle veröffentlichten Interventionsstudien identifiziert und ihre Methoden kritisch bewertet sowie ihre Ergebnisse zusammengefasst wurden.MethodenWir durchsuchten systematisch die größte medizinische Literaturdatenbank MEDLINE, weitere relevante Internetquellen und graue Literatur nach randomisierten und nicht-randomisierten Studien, mit oder ohne Kontrollgruppen, bis September 2021 und ohne sprachliche Einschränkungen. Weitere Einschlusskriterien waren erwachsene Patienten mit Sodbrennen, Trinkkur mit natürlichem Mineralwasser als Intervention, im Vergleich zu keiner oder anderen Interventionen (care-as-usual, Warteliste). Wir definierten die Abnahme der Symptome des Sodbrennens und die Dauer der Krankheitsepisoden als primäre und die Lebensqualität als sekundäre Endpunkte. Zwei Gutachter bewerteten unabhängig voneinander die Qualität der Studien (Verzerrungsrisiko) anhand der National Institutes of Health-Study Quality Assessment Tools.ErgebnisseNeun Studien mit 393 Patienten aus Italien, Russland, der Ukraine und Deutschland erfüllten alle Einschlusskriterien. Wir identifizierten drei randomisierte kontrollierte Studien (alle mit schlechter methodischer Qualität) sowie sechs Vorher-Nachher-Studien (Prä-/Post-Studien) ohne Kontrollgruppe. Die Interventionsgruppen der drei randomisierten Vergleichsstudien schienen eine stärkere Verringerung der selbstberichteten Symptome und der Dauer der Episoden des Sodbrennens zu zeigen als die jeweiligen Kontrollgruppen, allerdings waren sie alle von schlechter methodischer Qualität.SchlussfolgerungAuf der Grundlage der besten verfügbaren Belege aus klinischen Studien können wir das Trinken natürlicher Mineralwässer zur Behandlung von Sodbrennen weder empfehlen noch davon abraten. Die potenziellen Vorteile natürlicher Mineralwässer, die in einigen Studien mit geringerer Evidenz (z. B. ohne Kontrollgruppe) berichtet wurden, sollten durch qualitativ hochwertige randomisierte klinische Studien mit angemessenen Vergleichsgruppen und längeren Nachbeobachtungszeiträumen überprüft werden.}, } @article {pmid38470574, year = {2024}, author = {Pan, H and Wang, Y and Li, Z and Chu, X and Teng, B and Gao, H}, title = {A Complete Scheme for Multi-Character Classification Using EEG Signals From Speech Imagery.}, journal = {IEEE transactions on bio-medical engineering}, volume = {71}, number = {8}, pages = {2454-2462}, doi = {10.1109/TBME.2024.3376603}, pmid = {38470574}, issn = {1558-2531}, mesh = {Humans ; *Electroencephalography/methods ; *Signal Processing, Computer-Assisted ; *Speech/physiology ; *Brain-Computer Interfaces ; Algorithms ; Wavelet Analysis ; Imagination/physiology ; Adult ; Male ; Female ; Neural Networks, Computer ; }, abstract = {Some classification studies of brain-computer interface (BCI) based on speech imagery show potential for improving communication skills in patients with amyotrophic lateral sclerosis (ALS). However, current research on speech imagery is limited in scope and primarily focuses on vowels or a few selected words. In this paper, we propose a complete research scheme for multi-character classification based on EEG signals derived from speech imagery. Firstly, we record 31 speech imagery contents, including 26 alphabets and five commonly used punctuation marks, from seven subjects using a 32-channel electroencephalogram (EEG) device. Secondly, we introduce the wavelet scattering transform (WST), which shares a structural resemblance to Convolutional Neural Networks (CNNs), for feature extraction. The WST is a knowledge-driven technique that preserves high-frequency information and maintains the deformation stability of EEG signals. To reduce the dimensionality of wavelet scattering coefficient features, we employ Kernel Principal Component Analysis (KPCA). Finally, the reduced features are fed into an Extreme Gradient Boosting (XGBoost) classifier within a multi-classification framework. The XGBoost classifier is optimized through hyperparameter tuning using grid search and 10-fold cross-validation, resulting in an average accuracy of 78.73% for the multi-character classification task. We utilize t-Distributed Stochastic Neighbor Embedding (t-SNE) technology to visualize the low-dimensional representation of multi-character speech imagery. This visualization effectively enables us to observe the clustering of similar characters. The experimental results demonstrate the effectiveness of our proposed multi-character classification scheme. Furthermore, our classification categories and accuracy exceed those reported in existing research.}, } @article {pmid38470552, year = {2024}, author = {Zou, W and Li, M and Wang, X and Lu, H and Hao, Y and Chen, D and Zhu, S and Ji, D and Zhang, Z and Zhou, P and Cao, Y}, title = {Preimplantation genetic testing for monogenic disorders (PGT-M) offers an alternative strategy to prevent children from being born with hereditary neurological diseases or metabolic diseases dominated by nervous system phenotypes: a retrospective study.}, journal = {Journal of assisted reproduction and genetics}, volume = {41}, number = {5}, pages = {1245-1259}, pmid = {38470552}, issn = {1573-7330}, support = {82001635//the National Natural Science Foundation of China/ ; 2021YFC2700901//the National Key R&D Program of China/ ; 202204295107020012//the Clinical Medical research transformation Project of Anhui Province/ ; 2022LCX015//the Foundation for Selected Scientists Studying Abroad of Anhui Province/ ; gxyqZD2022027//Program for Outstanding Young Talents in University of Anhui/ ; 202003a07020012//Major Science and Technology Project of Anhui province/ ; }, mesh = {Humans ; *Preimplantation Diagnosis/methods ; Female ; Pregnancy ; *Genetic Testing/methods ; *Metabolic Diseases/genetics/pathology ; Retrospective Studies ; Male ; Nervous System Diseases/genetics ; Phenotype ; Adult ; Child ; Embryo Transfer ; Mutation/genetics ; }, abstract = {BACKGROUND: Preimplantation genetic testing for monogenic disorders (PGT-M) is now widely used as an effective strategy to prevent various monogenic or chromosomal diseases.

MATERIAL AND METHODS: In this retrospective study, couples with a family history of hereditary neurological diseases or metabolic diseases dominated by nervous system phenotypes and/or carrying the pathogenic genes underwent PGT-M to prevent children from inheriting disease-causing gene mutations from their parents and developing known genetic diseases. After PGT-M, unaffected (i.e., normal) embryos after genetic detection were transferred into the uterus of their corresponding mothers.

RESULTS: A total of 43 carrier couples with the following hereditary neurological diseases or metabolic diseases dominated by nervous system phenotypes underwent PGT-M: Duchenne muscular dystrophy (13 families); methylmalonic acidemia (7 families); spinal muscular atrophy (5 families); infantile neuroaxonal dystrophy and intellectual developmental disorder (3 families each); Cockayne syndrome (2 families); Menkes disease, spinocerebellar ataxia, glycine encephalopathy with epilepsy, Charcot-Marie-Tooth disease, mucopolysaccharidosis, Aicardi-Goutieres syndrome, adrenoleukodystrophy, phenylketonuria, amyotrophic lateral sclerosis, and Dravet syndrome (1 family each). After 53 PGT-M cycles, the final transferable embryo rate was 12.45%, the clinical pregnancy rate was 74.19%, and the live birth rate was 89.47%; a total of 18 unaffected (i.e., healthy) children were born to these families.

CONCLUSIONS: This study highlights the importance of PGT-M in preventing children born with hereditary neurological diseases or metabolic diseases dominated by nervous system phenotypes.}, } @article {pmid38470068, year = {2024}, author = {Van Damme, P and Al-Chalabi, A and Andersen, PM and Chiò, A and Couratier, P and De Carvalho, M and Hardiman, O and Kuźma-Kozakiewicz, M and Ludolph, A and McDermott, CJ and Mora, JS and Petri, S and Probyn, K and Reviers, E and Salachas, F and Silani, V and Tysnes, OB and van den Berg, LH and Villanueva, G and Weber, M}, title = {European Academy of Neurology (EAN) guideline on the management of amyotrophic lateral sclerosis in collaboration with European Reference Network for Neuromuscular Diseases (ERN EURO-NMD).}, journal = {European journal of neurology}, volume = {31}, number = {6}, pages = {e16264}, pmid = {38470068}, issn = {1468-1331}, support = {//ERN Euro-NMD/ ; //European Academy of Neurology/ ; //ALS Liga Belgium/ ; //EUpALS/ ; //ENCALS/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/therapy ; Humans ; Europe ; Neurology/standards/methods ; Neuromuscular Diseases/therapy ; }, abstract = {BACKGROUND: This update of the guideline on the management of amyotrophic lateral sclerosis (ALS) was commissioned by the European Academy of Neurology (EAN) and prepared in collaboration with the European Reference Network for Neuromuscular Diseases (ERN EURO-NMD) and the support of the European Network for the Cure ALS (ENCALS) and the European Organization for Professionals and Patients with ALS (EUpALS).

METHODS: Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology was used to assess the effectiveness of interventions for ALS. Two systematic reviewers from Cochrane Response supported the guideline panel. The working group identified a total of 26 research questions, performed systematic reviews, assessed the quality of the available evidence, and made specific recommendations. Expert consensus statements were provided where insufficient evidence was available.

RESULTS: A guideline mapping effort revealed only one other ALS guideline that used GRADE methodology (a National Institute for Health and Care Excellence [NICE] guideline). The available evidence was scarce for many research questions. Of the 26 research questions evaluated, the NICE recommendations could be adapted for 8 questions. Other recommendations required updates of existing systematic reviews or de novo reviews. Recommendations were made on currently available disease-modifying treatments, multidisciplinary care, nutritional and respiratory support, communication aids, psychological support, treatments for common ALS symptoms (e.g., muscle cramps, spasticity, pseudobulbar affect, thick mucus, sialorrhea, pain), and end-of-life management.

CONCLUSIONS: This update of the guideline using GRADE methodology provides a framework for the management of ALS. The treatment landscape is changing rapidly, and further updates will be prepared when additional evidence becomes available.}, } @article {pmid38469975, year = {2024}, author = {Nigri, A and Stanziano, M and Fedeli, D and Manera, U and Ferraro, S and Medina Carrion, JP and Palermo, S and Lequio, L and Denegri, F and Agosta, F and Spinelli, EG and Filippi, M and Grisoli, M and Valentini, MC and De Mattei, F and Canosa, A and Calvo, A and Chiò, A and Bruzzone, MG and Moglia, C}, title = {Distinct neural signatures of pulvinar in C9orf72 amyotrophic lateral sclerosis mutation carriers and noncarriers.}, journal = {European journal of neurology}, volume = {31}, number = {6}, pages = {e16266}, pmid = {38469975}, issn = {1468-1331}, support = {2017SNW5MB//Ministero dell'Università e della Ricerca/ ; FP7/2007-2013//European Commission's Health Seventh Framework Programme/ ; 259867//European Commission's Health Seventh Framework Programme/ ; GR-2019-12371291//Ministero della Salute/ ; RF-2016-02362405//Ministero della Salute/ ; RRC//Ministero della Salute/ ; }, mesh = {Aged ; Female ; Humans ; Male ; Middle Aged ; *Amyotrophic Lateral Sclerosis/genetics/diagnostic imaging/physiopathology/pathology ; *C9orf72 Protein/genetics ; Frontotemporal Dementia/genetics/physiopathology/diagnostic imaging/pathology ; Heterozygote ; *Magnetic Resonance Imaging ; *Mutation ; *Pulvinar/diagnostic imaging/physiopathology/pathology ; }, abstract = {BACKGROUND AND PURPOSE: Thalamic alterations have been reported as a major feature in presymptomatic and symptomatic patients carrying the C9orf72 mutation across the frontotemporal dementia-amyotrophic lateral sclerosis (ALS) spectrum. Specifically, the pulvinar, a high-order thalamic nucleus and timekeeper for large-scale cortical networks, has been hypothesized to be involved in C9orf72-related neurodegenerative diseases. We investigated whether pulvinar volume can be useful for differential diagnosis in ALS C9orf72 mutation carriers and noncarriers and how underlying functional connectivity changes affect this region.

METHODS: We studied 19 ALS C9orf72 mutation carriers (ALSC9+) accurately matched with wild-type ALS (ALSC9-) and ALS mimic (ALSmimic) patients using structural and resting-state functional magnetic resonance imaging data. Pulvinar volume was computed using automatic segmentation. Seed-to-voxel functional connectivity analyses were performed using seeds from a pulvinar functional parcellation.

RESULTS: Pulvinar structural integrity had high discriminative values for ALSC9+ patients compared to ALSmimic (area under the curve [AUC] = 0.86) and ALSC9- (AUC = 0.77) patients, yielding a volume cutpoint of approximately 0.23%. Compared to ALSmimic, ALSC9- showed increased anterior, inferior, and lateral pulvinar connections with bilateral occipital-temporal-parietal regions, whereas ALSC9+ showed no differences. ALSC9+ patients when compared to ALSC9- patients showed reduced pulvinar-occipital connectivity for anterior and inferior pulvinar seeds.

CONCLUSIONS: Pulvinar volume could be a differential biomarker closely related to the C9orf72 mutation. A pulvinar-cortical circuit dysfunction might play a critical role in disease progression and development, in both the genetic phenotype and ALS wild-type patients.}, } @article {pmid38469573, year = {2024}, author = {Broce, IJ and Sirkis, DW and Nillo, RM and Bonham, LW and Lee, SE and Miller, BL and Castruita, PA and Sturm, VE and Sugrue, LS and Desikan, RS and Yokoyama, JS}, title = {C9orf72 gene networks in the human brain correlate with cortical thickness in C9-FTD and implicate vulnerable cell types.}, journal = {Frontiers in neuroscience}, volume = {18}, number = {}, pages = {1258996}, pmid = {38469573}, issn = {1662-4548}, support = {R01 AG052496/AG/NIA NIH HHS/United States ; T32 AG058529/AG/NIA NIH HHS/United States ; R25 NS117367/NS/NINDS NIH HHS/United States ; R01 AG058233/AG/NIA NIH HHS/United States ; K01 AG070376/AG/NIA NIH HHS/United States ; }, abstract = {INTRODUCTION: A hexanucleotide repeat expansion (HRE) intronic to chromosome 9 open reading frame 72 (C9orf72) is recognized as the most common genetic cause of amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and ALS-FTD. Identifying genes that show similar regional co-expression patterns to C9orf72 may help identify novel gene targets and biological mechanisms that mediate selective vulnerability to ALS and FTD pathogenesis.

METHODS: We leveraged mRNA expression data in healthy brain from the Allen Human Brain Atlas to evaluate C9orf72 co-expression patterns. To do this, we correlated average C9orf72 expression values in 51 regions across different anatomical divisions (cortex, subcortex, and cerebellum) with average gene expression values for 15,633 protein-coding genes, including 54 genes known to be associated with ALS, FTD, or ALS-FTD. We then performed imaging transcriptomic analyses to evaluate whether the identified C9orf72 co-expressed genes correlated with patterns of cortical thickness in symptomatic C9orf72 pathogenic HRE carriers (n = 19) compared to controls (n = 23). Lastly, we explored whether genes with significant C9orf72 imaging transcriptomic correlations (i.e., "C9orf72 imaging transcriptomic network") were enriched in specific cell populations in the brain and enriched for specific biological and molecular pathways.

RESULTS: A total of 2,120 genes showed an anatomical distribution of gene expression in the brain similar to C9orf72 and significantly correlated with patterns of cortical thickness in C9orf72 HRE carriers. This C9orf72 imaging transcriptomic network was differentially expressed in cell populations previously implicated in ALS and FTD, including layer 5b cells, cholinergic neurons in the spinal cord and brainstem and medium spiny neurons of the striatum, and was enriched for biological and molecular pathways associated with protein ubiquitination, autophagy, cellular response to DNA damage, endoplasmic reticulum to Golgi vesicle-mediated transport, among others.

CONCLUSION: Considered together, we identified a network of C9orf72 associated genes that may influence selective regional and cell-type-specific vulnerabilities in ALS/FTD.}, } @article {pmid38468173, year = {2024}, author = {Yu, Z and Zhang, H and Wang, Y}, title = {In Reply to the Letter to the Editor Regarding "Cervical Spondylotic Amyotrophy Initially Misdiagnosed as Amyotrophic Lateral Sclerosis".}, journal = {World neurosurgery}, volume = {183}, number = {}, pages = {270}, doi = {10.1016/j.wneu.2023.12.140}, pmid = {38468173}, issn = {1878-8769}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis ; Muscular Atrophy ; Muscle, Skeletal ; *Spondylosis/diagnosis ; Diagnostic Errors ; }, } @article {pmid38468172, year = {2024}, author = {Chang, MC}, title = {Letter to the Editor Regarding "Cervical Spondylotic Amyotrophy Initially Misdiagnosed as Amyotrophic Lateral Sclerosis".}, journal = {World neurosurgery}, volume = {183}, number = {}, pages = {269}, doi = {10.1016/j.wneu.2023.10.122}, pmid = {38468172}, issn = {1878-8769}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis ; Muscular Atrophy ; Muscle, Skeletal ; *Spondylosis/diagnosis ; Diagnostic Errors ; Cervical Vertebrae ; }, } @article {pmid38468041, year = {2024}, author = {Davidson, JM and Zhang, L and Yue, GH and Di Ieva, A}, title = {Fractal Dimension Studies of the Brain Shape in Aging and Neurodegenerative Diseases.}, journal = {Advances in neurobiology}, volume = {36}, number = {}, pages = {329-363}, pmid = {38468041}, issn = {2190-5215}, mesh = {Humans ; Adult ; *Neurodegenerative Diseases/diagnostic imaging/pathology ; Fractals ; Gray Matter/diagnostic imaging/pathology ; Aging ; Cerebellum/diagnostic imaging/pathology ; }, abstract = {The fractal dimension is a morphometric measure that has been used to investigate the changes of brain shape complexity in aging and neurodegenerative diseases. This chapter reviews fractal dimension studies in aging and neurodegenerative disorders in the literature. Research has shown that the fractal dimension of the left cerebral hemisphere increases until adolescence and then decreases with aging, while the fractal dimension of the right hemisphere continues to increase until adulthood. Studies in neurodegenerative diseases demonstrated a decline in the fractal dimension of the gray matter and white matter in Alzheimer's disease, amyotrophic lateral sclerosis, and spinocerebellar ataxia. In multiple sclerosis, the white matter fractal dimension decreases, but conversely, the fractal dimension of the gray matter increases at specific stages of disease. There is also a decline in the gray matter fractal dimension in frontotemporal dementia and multiple system atrophy of the cerebellar type and in the white matter fractal dimension in epilepsy and stroke. Region-specific changes in fractal dimension have also been found in Huntington's disease and Parkinson's disease. Associations were found between the fractal dimension and clinical scores, showing the potential of the fractal dimension as a marker to monitor brain shape changes in normal or pathological processes and predict cognitive or motor function.}, } @article {pmid38467696, year = {2024}, author = {Hilton, JBW and Kysenius, K and Liddell, JR and Mercer, SW and Paul, B and Beckman, JS and McLean, CA and White, AR and Donnelly, PS and Bush, AI and Hare, DJ and Roberts, BR and Crouch, PJ}, title = {Evidence for disrupted copper availability in human spinal cord supports Cu[II](atsm) as a treatment option for sporadic cases of ALS.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {5929}, pmid = {38467696}, issn = {2045-2322}, mesh = {Humans ; Mice ; Animals ; Copper/metabolism ; *Amyotrophic Lateral Sclerosis/metabolism ; Superoxide Dismutase/metabolism ; Superoxide Dismutase-1/genetics/metabolism ; *Neurodegenerative Diseases/metabolism ; Mice, Transgenic ; Spinal Cord/metabolism ; Ceruloplasmin/metabolism ; Disease Models, Animal ; *Thiosemicarbazones ; *Coordination Complexes ; }, abstract = {The copper compound Cu[II](atsm) has progressed to phase 2/3 testing for treatment of the neurodegenerative disease amyotrophic lateral sclerosis (ALS). Cu[II](atsm) is neuroprotective in mutant SOD1 mouse models of ALS where its activity is ascribed in part to improving availability of essential copper. However, SOD1 mutations cause only ~ 2% of ALS cases and therapeutic relevance of copper availability in sporadic ALS is unresolved. Herein we assessed spinal cord tissue from human cases of sporadic ALS for copper-related changes. We found that when compared to control cases the natural distribution of spinal cord copper was disrupted in sporadic ALS. A standout feature was decreased copper levels in the ventral grey matter, the primary anatomical site of neuronal loss in ALS. Altered expression of genes involved in copper handling indicated disrupted copper availability, and this was evident in decreased copper-dependent ferroxidase activity despite increased abundance of the ferroxidases ceruloplasmin and hephaestin. Mice expressing mutant SOD1 recapitulate salient features of ALS and the unsatiated requirement for copper in these mice is a biochemical target for Cu[II](atsm). Our results from human spinal cord indicate a therapeutic mechanism of action for Cu[II](atsm) involving copper availability may also be pertinent to sporadic cases of ALS.}, } @article {pmid38467605, year = {2024}, author = {Zhong, J and Wang, C and Zhang, D and Yao, X and Zhao, Q and Huang, X and Lin, F and Xue, C and Wang, Y and He, R and Li, XY and Li, Q and Wang, M and Zhao, S and Afridi, SK and Zhou, W and Wang, Z and Xu, Y and Xu, Z}, title = {PCDHA9 as a candidate gene for amyotrophic lateral sclerosis.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {2189}, pmid = {38467605}, issn = {2041-1723}, support = {32061143026, 31921002,32330038, 32394030//National Science Foundation of China | National Natural Science Foundation of China-Yunnan Joint Fund (NSFC-Yunnan Joint Fund)/ ; 82171412//National Science Foundation of China | National Natural Science Foundation of China-Yunnan Joint Fund (NSFC-Yunnan Joint Fund)/ ; 2021ZD0202300//Ministry of Science and Technology of the People's Republic of China (Chinese Ministry of Science and Technology)/ ; }, mesh = {Humans ; Mice ; Animals ; Aged ; *Amyotrophic Lateral Sclerosis/metabolism ; *Neurodegenerative Diseases/metabolism ; Mice, Transgenic ; Motor Neurons/metabolism ; Spinal Cord/metabolism ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease. To identify additional genetic factors, we analyzed exome sequences in a large cohort of Chinese ALS patients and found a homozygous variant (p.L700P) in PCDHA9 in three unrelated patients. We generated Pcdhα9 mutant mice harboring either orthologous point mutation or deletion mutation. These mice develop progressive spinal motor loss, muscle atrophy, and structural/functional abnormalities of the neuromuscular junction, leading to paralysis and early lethality. TDP-43 pathology is detected in the spinal motor neurons of aged mutant mice. Mechanistically, we demonstrate that Pcdha9 mutation causes aberrant activation of FAK and PYK2 in aging spinal cord, and dramatically reduced NKA-α1 expression in motor neurons. Our single nucleus multi-omics analysis reveals disturbed signaling involved in cell adhesion, ion transport, synapse organization, and neuronal survival in aged mutant mice. Together, our results present PCDHA9 as a potential ALS gene and provide insights into its pathogenesis.}, } @article {pmid38466778, year = {2024}, author = {Salaikumaran, MR and Gopal, PP}, title = {Rational Design of TDP-43 Derived α-Helical Peptide Inhibitors: An In Silico Strategy to Prevent TDP-43 Aggregation in Neurodegenerative Disorders.}, journal = {ACS chemical neuroscience}, volume = {15}, number = {6}, pages = {1096-1109}, pmid = {38466778}, issn = {1948-7193}, support = {R01 NS122907/NS/NINDS NIH HHS/United States ; }, mesh = {Humans ; Protein Conformation, alpha-Helical ; Molecular Docking Simulation ; *Peptides/pharmacology ; *Amyotrophic Lateral Sclerosis/metabolism ; DNA-Binding Proteins/metabolism ; }, abstract = {TDP-43, an essential RNA/DNA-binding protein, is central to the pathology of neurodegenerative diseases, such as amyotrophic lateral sclerosis and frontotemporal dementia. Pathological mislocalization and aggregation of TDP-43 disrupt RNA splicing, mRNA stability, and mRNA transport, thereby impairing neuronal function and survival. The formation of amyloid-like TDP-43 filaments is largely facilitated by the destabilization of an α-helical segment within the disordered C-terminal region. In this study, we hypothesized that preventing the destabilization of the α-helical domain could potentially halt the growth of these pathological filaments. To explore this, we utilized a range of in silico techniques to design and evaluate peptide-based therapeutics that bind to pathological TDP-43 amyloid-like filament crystal structures and resist β sheet conversion. Our computational approaches, including biophysical and secondary structure property prediction, molecular docking, 3D structure prediction, and molecular dynamics simulations, were used to assess the structure, stability, and binding affinity of these peptides in relation to pathological TDP-43 filaments. The results of our in silico analyses identified a selection of promising peptides which displayed a stable α-helical structure, exhibited an increased number of intramolecular hydrogen bonds within the helical domain, and demonstrated high binding affinities for pathological TDP-43 amyloid-like filaments. Molecular dynamics simulations provided further support for the structural and thermodynamic stability of these peptides, as they exhibited lower root-mean-square deviation and more favorable free energy landscapes over 300 ns. These findings establish α-helical propensity peptides as potential lead molecules for the development of novel therapeutics against TDP-43 aggregation. This structure-based computational approach for the rational design of peptide inhibitors opens a new direction in the search for effective interventions for ALS, FTD, and other related neurodegenerative diseases. The peptides identified as the most promising candidates in this study are currently subject to further testing and validation through both in vitro and in vivo experiments.}, } @article {pmid38466738, year = {2024}, author = {Pelletier, C and Shaw, S and Alsayegh, S and Brown, AJP and Lorenz, A}, title = {Candida auris undergoes adhesin-dependent and -independent cellular aggregation.}, journal = {PLoS pathogens}, volume = {20}, number = {3}, pages = {e1012076}, pmid = {38466738}, issn = {1553-7374}, support = {MR/M026663/1/MRC_/Medical Research Council/United Kingdom ; MR/M026663/2/MRC_/Medical Research Council/United Kingdom ; MR/V033417/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Humans ; *Antifungal Agents/therapeutic use ; *Candida/genetics ; Candida auris ; Virulence ; Drug Resistance, Fungal ; Adhesins, Bacterial/metabolism ; Microbial Sensitivity Tests ; }, abstract = {Candida auris is a fungal pathogen of humans responsible for nosocomial infections with high mortality rates. High levels of resistance to antifungal drugs and environmental persistence mean these infections are difficult to treat and eradicate from a healthcare setting. Understanding the life cycle and the genetics of this fungus underpinning clinically relevant traits, such as antifungal resistance and virulence, is of the utmost importance to develop novel treatments and therapies. Epidemiological and genomic studies have identified five geographical clades (I-V), which display phenotypic and genomic differences. Aggregation of cells, a phenotype primarily of clade III strains, has been linked to reduced virulence in some infection models. The aggregation phenotype has thus been associated with conferring an advantage for (skin) colonisation rather than for systemic infection. However, strains with different clade affiliations were compared to infer the effects of different morphologies on virulence. This makes it difficult to distinguish morphology-dependent causes from clade-specific or even strain-specific genetic factors. Here, we identify two different types of aggregation: one induced by antifungal treatment which is a result of a cell separation defect; and a second which is controlled by growth conditions and only occurs in strains with the ability to aggregate. The latter aggregation type depends on an ALS-family adhesin which is differentially expressed during aggregation in an aggregative C. auris strain. Finally, we demonstrate that macrophages cannot clear aggregates, suggesting that aggregation might after all provide a benefit during systemic infection and could facilitate long-term persistence in the host.}, } @article {pmid38465877, year = {2024}, author = {Young, CA and Chaouch, A and Mcdermott, CJ and Al-Chalabi, A and Chhetri, SK and Talbot, K and Harrower, T and Orrell, RW and Annadale, J and Hanemann, CO and Scalfari, A and Tennant, A and Mills, R and , }, title = {Dyspnea (breathlessness) in amyotrophic lateral sclerosis/motor neuron disease: prevalence, progression, severity, and correlates.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {25}, number = {5-6}, pages = {475-485}, pmid = {38465877}, issn = {2167-9223}, mesh = {Humans ; *Dyspnea/physiopathology/diagnosis/epidemiology/etiology ; Male ; Female ; *Amyotrophic Lateral Sclerosis/epidemiology/diagnosis/physiopathology/complications ; Middle Aged ; Aged ; *Disease Progression ; Prevalence ; *Severity of Illness Index ; Motor Neuron Disease/epidemiology/physiopathology/diagnosis/complications ; Quality of Life ; Adult ; }, abstract = {OBJECTIVE: Dyspnea, or breathlessness, is an important symptom in amyotrophic lateral sclerosis/motor neuron disease (ALS/MND). We examined the measurement properties of the Dyspnea-12.

METHODS: Rasch analysis enabled conversion of raw Dyspnea-12 scores to interval level metric equivalents. Converted data were used to perform trajectory modeling; those following different trajectories were compared for demographic, clinical, symptom, and functioning characteristics. Logistic regression examined differences between distinct trajectories.

RESULTS: In 1022 people, at baseline, mean metric Dyspnea-12 was 7.6 (SD 9.3). 49.8% had dyspnea, severe in 12.6%. Trajectory analysis over 28 months revealed three breathlessness trajectories: group 1 reported none at baseline/follow-up (42.7%); group 2 significantly increased over time (9.4%); group 3 had a much higher level at baseline which rose over follow-up (47.9%). Group 3 had worse outcomes on all symptoms, functioning and quality of life; compared to group 1, their odds of: respiratory onset sixfold greater; King's stage ≥3 2.9 greater; increased odds of being bothered by choking, head drop, fasciculations, and muscle cramps; fatigue and anxiety also elevated (p < .01).

CONCLUSION: Dyspnea is a cardinal symptom in ALS/MND and can be quickly measured using the Dyspnea-12. Raw scores can easily be converted to interval level measurement, for valid change scores and trajectory modeling. Dyspnea trajectories reveal different patterns, showing that clinical services must provide monitoring which is customized to individual patient need. Almost half of this large population had worsening dyspnea, confirming the importance of respiratory monitoring and interventions being integrated into routine ALS care.}, } @article {pmid38465478, year = {2024}, author = {Wendebourg, MJ and Weigel, M and Weidensteiner, C and Sander, L and Kesenheimer, E and Naumann, N and Haas, T and Madoerin, P and Braun, N and Neuwirth, C and Weber, M and Jahn, K and Kappos, L and Granziera, C and Schweikert, K and Sinnreich, M and Bieri, O and Schlaeger, R}, title = {Cervical and thoracic spinal cord gray matter atrophy is associated with disability in patients with amyotrophic lateral sclerosis.}, journal = {European journal of neurology}, volume = {31}, number = {6}, pages = {e16268}, pmid = {38465478}, issn = {1468-1331}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnostic imaging/pathology/physiopathology/complications ; Female ; Middle Aged ; Male ; *Gray Matter/diagnostic imaging/pathology ; Aged ; *Magnetic Resonance Imaging ; *Atrophy/pathology ; Cervical Cord/diagnostic imaging/pathology ; Thoracic Vertebrae/diagnostic imaging ; Spinal Cord/diagnostic imaging/pathology ; Cervical Vertebrae/diagnostic imaging ; White Matter/diagnostic imaging/pathology ; }, abstract = {BACKGROUND AND PURPOSE: In amyotrophic lateral sclerosis (ALS), there is an unmet need for more precise patient characterization through quantitative, ideally operator-independent, assessments of disease extent and severity. Radially sampled averaged magnetization inversion recovery acquisitions (rAMIRA) magnetic resonance imaging enables gray matter (GM) and white matter (WM) area quantitation in the cervical and thoracic spinal cord (SC) with optimized contrast. We aimed to investigate rAMIRA-derived SC GM and SC WM areas and their association with clinical phenotype and disability in ALS.

METHODS: A total of 36 patients with ALS (mean [SD] age 61.7 [12.6] years, 14 women) and 36 healthy, age- and sex-matched controls (HCs; mean [SD] age 63.1 [12.1] years, 14 women) underwent two-dimensional axial rAMIRA imaging at the inter-vertebral disc levels C2/3-C5/C6 and the lumbar enlargement level Tmax. ALS Functional Rating Scale-revised (ALSFRS-R) score, muscle strength, and sniff nasal inspiratory pressure (SNIP) were assessed.

RESULTS: Compared to HCs, GM and WM areas were reduced in patients at all cervical levels (p < 0.0001). GM area (p = 0.0001), but not WM area, was reduced at Tmax. Patients with King's Stage 3 showed significant GM atrophy at all levels, while patients with King's Stage 1 showed significant GM atrophy selectively at Tmax. SC GM area was significantly associated with muscle force at corresponding myotomes. GM area at C3/C4 was associated with ALSFRS-R (p < 0.001) and SNIP (p = 0.0016).

CONCLUSION: Patients with ALS assessed by rAMIRA imaging show significant cervical and thoracic SC GM and SC WM atrophy. SC GM area correlates with muscle strength and clinical disability. GM area reduction at Tmax may be an early disease sign. Longitudinal studies are warranted.}, } @article {pmid38464738, year = {2023}, author = {Kekenadze, M and Rocca, C and Turchetti, V and Nagy, S and Kvirkvelia, N and Vashadze, S and Kvaratskhelia, E and Beridze, M and Kaiyrzhanov, R and Houlden, H}, title = {Analysis of C9orf72 repeat expansions in Georgian patients with Amyotrophic lateral sclerosis (ALS).}, journal = {F1000Research}, volume = {12}, number = {}, pages = {1113}, pmid = {38464738}, issn = {2046-1402}, support = {/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics ; *C9orf72 Protein/genetics ; Middle Aged ; *DNA Repeat Expansion/genetics ; Aged ; Male ; Female ; Adult ; Aged, 80 and over ; Georgia (Republic) ; *Proteins/genetics ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a fatal progressive neurodegenerative disorder that affects the upper and lower motor neurons. Several genetic risk factors have been identified in the past decade with a hexanucleotide repeat expansion in the C9orf72 gene being the most significant. However, the presence of C9orf72 repeat expansion has not been examined in the Transcaucasian region, therefore we aimed to analyse its frequency in Georgian patients with ALS.

METHODS: We included 64 self-reported Georgian patients with ALS from different parts of the country, fulfilling the Gold Coast criteria. To investigate the presence of an expanded GGGGCC hexanucleotide repeat in the non-coding region of the C9orf72 gene, we performed Repeat-Primed PCR (RP-PCR).

RESULTS: In total, 62 sporadic and two familial ALS cases were identified. Patients were aged 26 to 84 years with a mean age of 58.3 years at disease onset. Bulbar onset was observed in 21.88%, upper limb onset in 34.38%, and lower limb onset in 43.75% of the patients. Frontotemporal dementia (FTD) fulfilling the Strong criteria was diagnosed in seven patients (10.94%). C9orf72 repeat expansion was detected in only one case using RP-PCR; the patient had a family history of dementia.

CONCLUSIONS: Our results indicate that C9orf72 hexanucleotide expansion does not belong to the major genetic risk factor of ALS in Georgian patients. Further genetic studies in a bigger study population are needed to reveal the genetic causes of ALS in the Transcaucasian population.}, } @article {pmid38464233, year = {2024}, author = {Jang, DG and Dou, J and Koubek, EJ and Teener, S and Zhao, L and Bakulski, KM and Mukherjee, B and Batterman, SA and Feldman, EL and Goutman, SA}, title = {Metal mixtures associate with higher amyotrophic lateral sclerosis risk and mortality independent of genetic risk and correlate to self-reported exposures: a case-control study.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, pmid = {38464233}, support = {R01TS000344/ACL/ACL HHS/United States ; R01 ES030049/ES/NIEHS NIH HHS/United States ; P30 ES017885/ES/NIEHS NIH HHS/United States ; P30 CA023108/CA/NCI NIH HHS/United States ; K23 ES027221/ES/NIEHS NIH HHS/United States ; R01 NS127188/NS/NINDS NIH HHS/United States ; R01 TS000344/TS/ATSDR CDC HHS/United States ; }, abstract = {BACKGROUND: The pathogenesis of amyotrophic lateral sclerosis (ALS) involves both genetic and environmental factors. This study investigates associations between metal measures in plasma and urine, ALS risk and survival, and exposure sources.

METHODS: Participants with and without ALS from Michigan provided plasma and urine samples for metal measurement via inductively coupled plasma mass spectrometry. Odds and hazard ratios for each metal were computed using risk and survival models. Environmental risk scores (ERS) were created to evaluate the association between exposure mixtures and ALS risk and survival and exposure source. ALS (ALS-PGS) and metal (metal-PGS) polygenic risk scores were constructed from an independent genome-wide association study and relevant literature-selected SNPs.

RESULTS: Plasma and urine samples from 454 ALS and 294 control participants were analyzed. Elevated levels of individual metals, including copper, selenium, and zinc, significantly associated with ALS risk and survival. ERS representing metal mixtures strongly associated with ALS risk (plasma, OR=2.95, CI=2.38-3.62, p<0.001; urine, OR=3.10, CI=2.43-3.97, p<0.001) and poorer ALS survival (plasma, HR=1.42, CI=1.24-1.63, p<0.001; urine, HR=1.52, CI=1.31-1.76, p<0.001). Addition of the ALS-PGS or metal-PGS did not alter the significance of metals with ALS risk and survival. Occupations with high potential of metal exposure associated with elevated ERS. Additionally, occupational and non-occupational metal exposures associated with measured plasma and urine metals.

CONCLUSION: Metals in plasma and urine associated with increased ALS risk and reduced survival, independent of genetic risk, and correlated with occupational and non-occupational metal exposures. These data underscore the significance of metal exposure in ALS risk and progression.}, } @article {pmid38464104, year = {2025}, author = {Das, T and Zaidi, FK and Farag, M and Ruff, KM and Mahendran, TS and Singh, A and Gui, X and Messing, J and Paul Taylor, J and Banerjee, PR and Pappu, RV and Mittag, T}, title = {Tunable metastability of condensates reconciles their dual roles in amyloid fibril formation.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {38464104}, issn = {2692-8205}, support = {P30 CA021765/CA/NCI NIH HHS/United States ; R01 NS121114/NS/NINDS NIH HHS/United States ; R35 GM138186/GM/NIGMS NIH HHS/United States ; R35 NS097974/NS/NINDS NIH HHS/United States ; }, abstract = {Stress granules form via co-condensation of RNA-binding proteins containing prion-like low complexity domains (PLCDs) with RNA molecules. Homotypic interactions among PLCDs can drive amyloid fibril formation that is enhanced by ALS-associated mutations. We report that condensation- versus fibril-driving homotypic interactions are separable for A1-LCD, the PLCD of hnRNPA1. Separable interactions lead to thermodynamically metastable condensates and globally stable fibrils. Interiors of condensates suppress fibril formation whereas interfaces have the opposite effect. ALS-associated mutations enhance the stability of fibrils and weaken condensate metastability, thus enhancing the rate of fibril formation. We designed mutations to enhance A1-LCD condensate metastability and discovered that stress granule disassembly in cells can be restored even when the designed variants carry ALS-causing mutations. Therefore, fibril formation can be suppressed by condensate interiors that function as sinks. Condensate sink potentials are influenced by their metastability, which is tunable through separable interactions even among minority components of stress granules.}, } @article {pmid38464028, year = {2024}, author = {Silvestri, B and Mochi, M and Mawrie, D and de Turris, V and Colantoni, A and Borhy, B and Medici, M and Anderson, EN and Garone, MG and Zammerilla, CP and Pandey, UB and Rosa, A}, title = {HuD (ELAVL4) gain-of-function impairs neuromuscular junctions and induces apoptosis in in vitro and in vivo models of amyotrophic lateral sclerosis.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {38464028}, issn = {2692-8205}, support = {R01 NS081303/NS/NINDS NIH HHS/United States ; }, abstract = {Early defects at the neuromuscular junction (NMJ) are among the first hallmarks of the progressive neurodegenerative disease amyotrophic lateral sclerosis (ALS). According to the "dying back" hypothesis, disruption of the NMJ not only precedes, but is also a trigger for the subsequent degeneration of the motoneuron in both sporadic and familial ALS, including ALS caused by the severe FUS pathogenic variant P525L. However, the mechanisms linking genetic and environmental factors to NMJ defects remain elusive. By taking advantage of co-cultures of motoneurons and skeletal muscle derived from human induced pluripotent stem cells (iPSCs), we show that the neural RNA binding protein HuD (ELAVL4) may underlie NMJ defects and apoptosis in FUS-ALS. HuD overexpression in motoneurons phenocopies the severe FUS[P525L] mutation, while HuD knockdown in FUS[P525L] co-cultures produces phenotypic rescue. We validated these findings in vivo in a Drosophila FUS-ALS model. Neuronal-restricted overexpression of the HuD-related gene, elav, produces per se a motor phenotype, while neuronal-restricted elav knockdown significantly rescues motor dysfunction caused by FUS. Finally, we show that HuD levels increase upon oxidative stress in human motoneurons and in sporadic ALS patients with an oxidative stress signature. On these bases, we propose HuD as an important player downstream of FUS mutation in familial ALS, with potential implications for sporadic ALS related to oxidative stress.}, } @article {pmid38463699, year = {2024}, author = {Van Schoor, E and Strubbe, D and Braems, E and Weishaupt, J and Ludolph, AC and Van Damme, P and Thal, DR and Bercier, V and Van Den Bosch, L}, title = {TUBA4A downregulation as observed in ALS post-mortem motor cortex causes ALS-related abnormalities in zebrafish.}, journal = {Frontiers in cellular neuroscience}, volume = {18}, number = {}, pages = {1340240}, pmid = {38463699}, issn = {1662-5102}, abstract = {Disease-associated variants of TUBA4A (alpha-tubulin 4A) have recently been identified in familial ALS. Interestingly, a downregulation of TUBA4A protein expression was observed in familial as well as sporadic ALS brain tissue. To investigate whether a decreased TUBA4A expression could be a driving factor in ALS pathogenesis, we assessed whether TUBA4A knockdown in zebrafish could recapitulate an ALS-like phenotype. For this, we injected an antisense oligonucleotide morpholino in zebrafish embryos targeting the zebrafish TUBA4A orthologue. An antibody against synaptic vesicle 2 was used to visualize motor axons in the spinal cord, allowing the analysis of embryonic ventral root projections. Motor behavior was assessed using the touch-evoked escape response. In post-mortem ALS motor cortex, we observed reduced TUBA4A levels. The knockdown of the zebrafish TUBA4A orthologue induced a motor axonopathy and a significantly disturbed motor behavior. Both phenotypes were dose-dependent and could be rescued by the addition of human wild-type TUBA4A mRNA. Thus, TUBA4A downregulation as observed in ALS post-mortem motor cortex could be modeled in zebrafish and induced a motor axonopathy and motor behavior defects reflecting a motor neuron disease phenotype, as previously described in embryonic zebrafish models of ALS. The rescue with human wild-type TUBA4A mRNA suggests functional conservation and strengthens the causal relation between TUBA4A protein levels and phenotype severity. Furthermore, the loss of TUBA4A induces significant changes in post-translational modifications of tubulin, such as acetylation, detyrosination and polyglutamylation. Our data unveil an important role for TUBA4A in ALS pathogenesis, and extend the relevance of TUBA4A to the majority of ALS patients, in addition to cases bearing TUBA4A mutations.}, } @article {pmid38463392, year = {2024}, author = {Chen, Y and Mateski, J and Gerace, L and Wheeler, J and Burl, J and Prakash, B and Svedin, C and Amrick, R and Adams, BD}, title = {Non-coding RNAs and neuroinflammation: implications for neurological disorders.}, journal = {Experimental biology and medicine (Maywood, N.J.)}, volume = {249}, number = {}, pages = {10120}, pmid = {38463392}, issn = {1535-3699}, mesh = {Humans ; Neuroinflammatory Diseases ; *Nervous System Diseases/genetics ; Microglia/metabolism ; *MicroRNAs/genetics/metabolism ; Cytokines/metabolism ; Chemokines/metabolism ; }, abstract = {Neuroinflammation is considered a balanced inflammatory response important in the intrinsic repair process after injury or infection. Under chronic states of disease, injury, or infection, persistent neuroinflammation results in a heightened presence of cytokines, chemokines, and reactive oxygen species that result in tissue damage. In the CNS, the surrounding microglia normally contain macrophages and other innate immune cells that perform active immune surveillance. The resulting cytokines produced by these macrophages affect the growth, development, and responsiveness of the microglia present in both white and gray matter regions of the CNS. Controlling the levels of these cytokines ultimately improves neurocognitive function and results in the repair of lesions associated with neurologic disease. MicroRNAs (miRNAs) are master regulators of the genome and subsequently control the activity of inflammatory responses crucial in sustaining a robust and acute immunological response towards an acute infection while dampening pathways that result in heightened levels of cytokines and chemokines associated with chronic neuroinflammation. Numerous reports have directly implicated miRNAs in controlling the abundance and activity of interleukins, TGF-B, NF-kB, and toll-like receptor-signaling intrinsically linked with the development of neurological disorders such as Parkinson's, ALS, epilepsy, Alzheimer's, and neuromuscular degeneration. This review is focused on discussing the role miRNAs play in regulating or initiating these chronic neurological states, many of which maintain the level and/or activity of neuron-specific secondary messengers. Dysregulated miRNAs present in the microglia, astrocytes, oligodendrocytes, and epididymal cells, contribute to an overall glial-specific inflammatory niche that impacts the activity of neuronal conductivity, signaling action potentials, neurotransmitter robustness, neuron-neuron specific communication, and neuron-muscular connections. Understanding which miRNAs regulate microglial activation is a crucial step forward in developing non-coding RNA-based therapeutics to treat and potentially correct the behavioral and cognitive deficits typically found in patients suffering from chronic neuroinflammation.}, } @article {pmid38462589, year = {2024}, author = {Ding, F and Sun, Q and Long, C and Rasmussen, RN and Peng, S and Xu, Q and Kang, N and Song, W and Weikop, P and Goldman, SA and Nedergaard, M}, title = {Dysregulation of extracellular potassium distinguishes healthy ageing from neurodegeneration.}, journal = {Brain : a journal of neurology}, volume = {147}, number = {5}, pages = {1726-1739}, pmid = {38462589}, issn = {1460-2156}, support = {U19 NS128613/NS/NINDS NIH HHS/United States ; R01AT012312/NH/NIH HHS/United States ; R01 NS110776/NS/NINDS NIH HHS/United States ; R01 AT011439/AT/NCCIH NIH HHS/United States ; R01 AT012312/AT/NCCIH NIH HHS/United States ; R01 HL122578/HL/NHLBI NIH HHS/United States ; R01 AG072298/AG/NIA NIH HHS/United States ; }, mesh = {Animals ; *Potassium/metabolism ; *Aging/metabolism ; Mice ; *Neurodegenerative Diseases/metabolism/genetics ; Amyotrophic Lateral Sclerosis/metabolism/genetics ; Alzheimer Disease/metabolism/genetics ; Mice, Transgenic ; Potassium Channels, Inwardly Rectifying/metabolism/genetics ; Male ; Mice, Inbred C57BL ; Neurons/metabolism ; Humans ; Disease Models, Animal ; Cerebral Cortex/metabolism ; Huntington Disease/metabolism/genetics ; Female ; Astrocytes/metabolism ; Kcnj10 Channel ; }, abstract = {Progressive neuronal loss is a hallmark feature distinguishing neurodegenerative diseases from normal ageing. However, the underlying mechanisms remain unknown. Extracellular K+ homeostasis is a potential mediator of neuronal injury as K+ elevations increase excitatory activity. The dysregulation of extracellular K+ and potassium channel expressions during neurodegeneration could contribute to this distinction. Here we measured the cortical extracellular K+ concentration ([K+]e) in awake wild-type mice as well as murine models of neurodegeneration using K+-sensitive microelectrodes. Unexpectedly, aged wild-type mice exhibited significantly lower cortical [K+]e than young mice. In contrast, cortical [K+]e was consistently elevated in Alzheimer's disease (APP/PS1), amyotrophic lateral sclerosis (ALS) (SOD1G93A) and Huntington's disease (R6/2) models. Cortical resting [K+]e correlated inversely with neuronal density and the [K+]e buffering rate but correlated positively with the predicted neuronal firing rate. Screening of astrocyte-selective genomic datasets revealed a number of potassium channel genes that were downregulated in these disease models but not in normal ageing. In particular, the inwardly rectifying potassium channel Kcnj10 was downregulated in ALS and Huntington's disease models but not in normal ageing, while Fxyd1 and Slc1a3, each of which acts as a negative regulator of potassium uptake, were each upregulated by astrocytes in both Alzheimer's disease and ALS models. Chronic elevation of [K+]e in response to changes in gene expression and the attendant neuronal hyperexcitability may drive the neuronal loss characteristic of these neurodegenerative diseases. These observations suggest that the dysregulation of extracellular K+ homeostasis in a number of neurodegenerative diseases could be due to aberrant astrocytic K+ buffering and as such, highlight a fundamental role for glial dysfunction in neurodegeneration.}, } @article {pmid38461796, year = {2024}, author = {Saranya, KR and Vimina, ER and Pinto, FR}, title = {TransNeT-CGP: A cluster-based comorbid gene prioritization by integrating transcriptomics and network-topological features.}, journal = {Computational biology and chemistry}, volume = {110}, number = {}, pages = {108038}, doi = {10.1016/j.compbiolchem.2024.108038}, pmid = {38461796}, issn = {1476-928X}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics ; Protein Interaction Maps/genetics ; Cluster Analysis ; Transcriptome/genetics ; Algorithms ; Gene Regulatory Networks ; Female ; Computational Biology ; Comorbidity ; Muscular Atrophy, Spinal/genetics ; Ovarian Neoplasms/genetics ; }, abstract = {The local disruptions caused by the genes of one disease can influence the pathways associated with the other diseases resulting in comorbidity. For gene therapies, it is necessary to prioritize the key genes that regulate common biological mechanisms to tackle the issues caused by overlapping diseases. This work proposes a clustering-based computational approach for prioritising the comorbid genes within the overlapping disease modules by analyzing Protein-Protein Interaction networks. For this, a sub-network with gene interactions of the disease pair was extracted from the interactome. The edge weights are assigned by combining the pairwise gene expression correlation and betweenness centrality scores. Further, a weighted graph clustering algorithm is applied and dominant nodes of high-density clusters are ranked based on clustering coefficients and neighborhood connectivity. Case studies based on neurodegenerative diseases such as Amyotrophic Lateral Sclerosis- Spinal Muscular Atrophy (ALS-SMA) pair and cancers such as Ovarian Carcinoma-Invasive Ductal Breast Carcinoma (OC-IDBC) pair were conducted to examine the efficacy of the proposed method. To identify the mechanistic role of top-ranked genes, we used Functional and Pathway enrichment analysis, connectivity analysis with leave-one-out (LOO) method, analysis of associated disease-related protein complexes, and prioritization tools such as TOPPGENE and Heml2.0. From pathway analysis, it was observed that the top 10 genes obtained using the proposed method were associated with 10 pathways in ALS-SMA comorbidity and 15 in the case of OC-IDBC, while that in similar methods like SAPDSB and S2B were 4, 6 respectively for ALS-SMA and 9, 10 respectively for OC-IDBC. In both case studies, 70 % of the disease-specific benchmark protein complexes were linked to top-ranked genes of the proposed method while that of SAPDSB and S2B were 55 % and 60 % respectively. Additionally, it was found that the removal of the top 10 genes disconnect the network into 14 distinct components in the case of ALS-SMA and 9 in the case of OC-IDBC. The experimental results shows that the proposed method can be effectively used for identifying key genes in comorbidity and can offer insights about the intricate molecular relationship driving comorbid diseases.}, } @article {pmid38461753, year = {2024}, author = {Eceiza, MV and Jimenez-Martinez, C and Gil-Monreal, M and Barco-Antoñanzas, M and Font-Farre, M and Huybrechts, M and van der Hoorn, RL and Cuypers, A and Royuela, M and Zabalza, A}, title = {Role of glutathione S-transferases in the mode of action of herbicides that inhibit amino acid synthesis in Amaranthus palmeri.}, journal = {Plant physiology and biochemistry : PPB}, volume = {208}, number = {}, pages = {108506}, doi = {10.1016/j.plaphy.2024.108506}, pmid = {38461753}, issn = {1873-2690}, mesh = {*Herbicides/pharmacology/metabolism ; *Amaranthus ; Hydrogen Peroxide/metabolism ; Herbicide Resistance ; Glyphosate ; Glutathione/metabolism ; Transferases/metabolism ; }, abstract = {Acetolactate synthase inhibitors (ALS inhibitors) and glyphosate are two classes of herbicides that act by inhibiting an enzyme in the biosynthetic pathway of branched-chain or aromatic amino acids, respectively. Besides amino acid synthesis inhibition, both herbicides trigger similar physiological effects in plants. The main aim of this study was to evaluate the role of glutathione metabolism, with special emphasis on glutathione S-transferases (GSTs), in the mode of action of glyphosate and ALS inhibitors in Amaranthus palmeri. For that purpose, plants belonging to a glyphosate-sensitive (GLS) and a glyphosate-resistant (GLR) population were treated with different doses of glyphosate, and plants belonging to an ALS-inhibitor sensitive (AIS) and an ALS-inhibitor resistant (AIR) population were treated with different doses of the ALS inhibitor nicosulfuron. Glutathione-related contents, GST activity, and related gene expressions (glutamate-cysteine ligase, glutathione reductase, Phi GST and Tau GST) were analysed in leaves. According to the results of the analytical determinations, there were virtually no basal differences between GLS and GLR plants or between AIS and AIR plants. Glutathione synthesis and turnover did not follow a clear pattern in response to herbicides, but GST activity and gene expression (especially Phi GSTs) increased with both herbicides in treated sensitive plants, possibly related to the rocketing H2O2 accumulation. As GSTs offered the clearest results, these were further investigated with a multiple resistant (MR) population, compressing target-site resistance to both glyphosate and the ALS inhibitor pyrithiobac. As in single-resistant plants, measured parameters in the MR population were unaffected by herbicides, meaning that the increase in GST activity and expression occurs due to herbicide interactions with the target enzymes.}, } @article {pmid38461154, year = {2024}, author = {Kodavati, M and Wang, H and Guo, W and Mitra, J and Hegde, PM and Provasek, V and Rao, VHM and Vedula, I and Zhang, A and Mitra, S and Tomkinson, AE and Hamilton, DJ and Van Den Bosch, L and Hegde, ML}, title = {FUS unveiled in mitochondrial DNA repair and targeted ligase-1 expression rescues repair-defects in FUS-linked motor neuron disease.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {2156}, pmid = {38461154}, issn = {2041-1723}, support = {R01 NS094535/NS/NINDS NIH HHS/United States ; R01 ES012512/ES/NIEHS NIH HHS/United States ; R01 NS088645/NS/NINDS NIH HHS/United States ; R03 AG064266/AG/NIA NIH HHS/United States ; RF1 NS112719/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Humans ; Mice ; *Amyotrophic Lateral Sclerosis/metabolism ; DNA, Mitochondrial/genetics ; Ligases/metabolism ; Mice, Transgenic ; *Mitochondrial Diseases ; *Motor Neuron Disease/genetics/metabolism ; Mutation ; *RNA-Binding Protein FUS/genetics/metabolism ; DNA Ligase ATP/genetics/metabolism ; }, abstract = {This study establishes the physiological role of Fused in Sarcoma (FUS) in mitochondrial DNA (mtDNA) repair and highlights its implications to the pathogenesis of FUS-associated neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS). Endogenous FUS interacts with and recruits mtDNA Ligase IIIα (mtLig3) to DNA damage sites within mitochondria, a relationship essential for maintaining mtDNA repair and integrity in healthy cells. Using ALS patient-derived FUS mutant cell lines, a transgenic mouse model, and human autopsy samples, we discovered that compromised FUS functionality hinders mtLig3's repair role, resulting in increased mtDNA damage and mutations. These alterations cause various manifestations of mitochondrial dysfunction, particularly under stress conditions relevant to disease pathology. Importantly, rectifying FUS mutations in patient-derived induced pluripotent cells (iPSCs) preserves mtDNA integrity. Similarly, targeted introduction of human DNA Ligase 1 restores repair mechanisms and mitochondrial activity in FUS mutant cells, suggesting a potential therapeutic approach. Our findings unveil FUS's critical role in mitochondrial health and mtDNA repair, offering valuable insights into the mechanisms underlying mitochondrial dysfunction in FUS-associated motor neuron disease.}, } @article {pmid38459794, year = {2024}, author = {Campagne, S}, title = {U1 snRNP Biogenesis Defects in Neurodegenerative Diseases.}, journal = {Chembiochem : a European journal of chemical biology}, volume = {25}, number = {9}, pages = {e202300864}, doi = {10.1002/cbic.202300864}, pmid = {38459794}, issn = {1439-7633}, mesh = {Animals ; Humans ; *Neurodegenerative Diseases/metabolism/pathology ; *Ribonucleoprotein, U1 Small Nuclear/metabolism/chemistry ; }, abstract = {The U1 small ribonucleoprotein (U1 snRNP) plays a pivotal role in the intricate process of gene expression, specifically within nuclear RNA processing. By initiating the splicing reaction and modulating 3'-end processing, U1 snRNP exerts precise control over RNA metabolism and gene expression. This ribonucleoparticle is abundantly present, and its complex biogenesis necessitates shuttling between the nuclear and cytoplasmic compartments. Over the past three decades, extensive research has illuminated the crucial connection between disrupted U snRNP biogenesis and several prominent human diseases, notably various neurodegenerative conditions. The perturbation of U1 snRNP homeostasis has been firmly established in diseases such as Spinal Muscular Atrophy, Pontocerebellar hypoplasia, and FUS-mediated Amyotrophic Lateral Sclerosis. Intriguingly, compelling evidence suggests a potential correlation in Fronto-temporal dementia and Alzheimer's disease as well. Although the U snRNP biogenesis pathway is conserved across all eukaryotic cells, neurons, in particular, appear to be highly susceptible to alterations in spliceosome homeostasis. In contrast, other cell types exhibit a greater resilience to such disturbances. This vulnerability underscores the intricate relationship between U1 snRNP dynamics and the health of neuronal cells, shedding light on potential avenues for understanding and addressing neurodegenerative disorders.}, } @article {pmid38459455, year = {2024}, author = {Nandeep, ER and Mamidi, RS and Pagidoju, S and Pamidi, S and Mummadi, MK and Reddy G, VR and Babu, CK and Reddy N, S and Geddam, JB}, title = {Comparison of Janani Suraksha Yojana (JSY) and augmented Arogya Laxmi scheme (ALS) in improving maternal and child health outcomes in urban settlements of Hyderabad, South India.}, journal = {BMC pregnancy and childbirth}, volume = {24}, number = {1}, pages = {188}, pmid = {38459455}, issn = {1471-2393}, support = {Grant A/C No. 241//ICMR-ICSSR Joint Research Programme/ ; Grant A/C No. 241//ICMR-ICSSR Joint Research Programme/ ; }, mesh = {Infant, Newborn ; Child ; Pregnancy ; Female ; Humans ; *Maternal Health Services ; Cross-Sectional Studies ; Prenatal Care ; India/epidemiology ; Outcome Assessment, Health Care ; Delivery, Obstetric ; }, abstract = {BACKGROUND: India accounts for the largest number of global neonatal deaths with around 20 per 1000 live births. To improve the utilization of government services for institutional deliveries, Augmented Arogya Laxmi Scheme (ALS) was launched in Telangana state of southern India. This study assessed the effectiveness of the Janani Suraksha Yojana (JSY), which combines cash assistance with delivery and post-delivery care, in comparison to ALS in improving the outcomes related to antenatal, natal, and postnatal care in urban settlements of Hyderabad, Telangana, southern India.

METHODS: This was a two-year cross-sectional study conducted in 14 urban settlements of Hyderabad city from September 2017- August 2019. All mothers delivered during the 18 months preceding the survey were enrolled after a written informed consent. Field investigators collected data on variables related to socio-demographic characteristics, awareness, and utilization of JSY and ALS programs. Variables related to antenatal history, antenatal care, complications during birth, delivery outcomes, newborn care, and postnatal care till 28 days were assessed. We used multivariable logistic regression model to examine the association between the different maternal, child, and socio-demographic characteristics of the two study groups.

RESULTS: A total of 926 mothers were beneficiaries of Janani Suraksha Yojana (JSY) program while 933 mothers were beneficiaries of augmented Arogya Laxmi Scheme (ALS). Mothers in ALS group (AOR 1.71; 95% CI 1.21-2.43) were at increased odds of having more than eight antenatal care (ANC) visits compared to the mothers availing JSY. Mothers in ALS group were at decreased odds of having complications like severe pain in the abdomen (AOR 0.43; 95% CI 0.22-0.86), swelling of legs or feet (AOR 0.59; 95% CI 0.44-0.80) compared to mothers in JSY group. Children of mothers in the ALS group had increased odds of receiving breastfeeding within 30 minutes of birth (AOR 1.46; 95% CI 1.13-1.88) compared to children of mothers in JSY group.

CONCLUSIONS: The newly launched augmented ALS led to the increased utilization of the government health facilities and improved the maternal and child health outcomes.}, } @article {pmid38458688, year = {2024}, author = {Xu, X and Zhao, B and Li, B and Shen, B and Qi, Z and Wang, J and Cui, H and Chen, S and Wang, G and Liu, X}, title = {Diverse ALS mutations and cross-and multiple-resistance to ALS and EPSPS inhibitors in flucarbazone‑sodium-resistant Bromus japonicus populations from Hebei province, China.}, journal = {Pesticide biochemistry and physiology}, volume = {199}, number = {}, pages = {105794}, doi = {10.1016/j.pestbp.2024.105794}, pmid = {38458688}, issn = {1095-9939}, mesh = {Bromus/metabolism ; *Herbicides/pharmacology ; Mutation ; China ; Herbicide Resistance/genetics ; *Acetolactate Synthase/metabolism ; *Sulfonamides ; *Triazoles ; }, abstract = {Japanese brome (Bromus japonicus) has become one of the main weeds in wheat fields in Hebei province of China and causes a large decrease of wheat production. A total of 44 putative resistant and 2 susceptible Japanese brome populations were collected in the 2021/2022 crop season from Hebei province of China to determine resistance levels to flucarbazone‑sodium and to investigate the diversity of acetolactate synthase (ALS) mutations, as well as to confirm the cross-and multiple-resistance levels to ALS and EPSPS (5-enolpyruvate shikimate-3-phosphate synthetase) inhibitors. Whole plant bioassay results showed that 15 out of 44 populations tested or 34% were resistant to flucarbazone‑sodium. The resistance indices of Japanese brome to flucarbazone‑sodium ranged from 43 to 1977. The resistant populations were mainly distributed in Baoding and Shijiazhuang districts, and there was only one resistant population in Langfang district. Resistant Japanese brome had diverse ALS mutations, including Pro-197-Ser, -Thr, -Arg and Asp-376-Glu. The incidence of Pro-197-Ser mutation was the highest at 68%. Application of the CYP450 inhibitor malathion suggested that CYP450 was involved in metabolic resistance in a population without an ALS mutation. The population with Pro-197-Thr mutation evolved weak cross-resistance to mesosulfuron-methyl and pyroxsulam, and it is in the process of evolving multiple-resistance to glyphosate.}, } @article {pmid38457872, year = {2024}, author = {Chaghazardi, M and Kashanian, S and Nazari, M and Omidfar, K and Shariati-Rad, M and Joseph, Y and Rahimi, P}, title = {Mercury (II) sensing using a simple turn-on fluorescent graphene oxide based aptasensor in serum and water samples.}, journal = {Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy}, volume = {313}, number = {}, pages = {124057}, doi = {10.1016/j.saa.2024.124057}, pmid = {38457872}, issn = {1873-3557}, mesh = {*Mercury ; Fluorescence Resonance Energy Transfer/methods ; Fluorometry/methods ; Water ; Limit of Detection ; Oligonucleotides ; *Graphite ; *Biosensing Techniques/methods ; *Aptamers, Nucleotide/metabolism ; }, abstract = {A simple, highly sensitive, and selective fluorometric aptasensing platform based on aptamer and graphene oxide (GO) is proposed for the determination of mercury (II) ion (Hg[2+]). In the designed assay, two aptamer probes, a carboxy-fluorescein (FAM) labeled aptamer (aptamer A) and its complementary (aptamer B) with partial complement containing several mismatches and GO as the quencher were used. In the absence of Hg[2+], both A and B aptamers were adsorbed on the surface of GO by π-π-stacking, leading to fluorescence quenching of FAM due to fluorescence resonance energy transfer (FRET). Upon exposure to Hg[2+], the A and B aptamer strands bind Hg[2+] and form T-Hg[2+]-T complexes, leading to the formation of a stable double-stranded aptamer. The double-stranded aptamer is detached from the GO surface, resulting in the recovery of FAM fluorescence. The fluorescence intensity (FI) of the developed sensor was correlated with the Hg[2+] concentration under optimized experimental conditions in two wide linear ranges, even in the presence of 10 divalent cations as interferences. The linear ranges were obtained from 200.0 to 900.0 fM and 5.0 to 33.0 pM, a limit of detection (LOD) of 106.0 fM, and a limit of quantification (LOQ) of 321.3 fM. The concentration of Hg[2+] was determined in five real samples containing three water and two serum samples, using spiking and standard addition methods and the results were compared with the spiked amounts and atomic absorption (AAS) as standard method respectively, with acceptable recoveries. Furthermore, in the standard addition method, to overcome the effects of matrix influence of real samples in quantitative predictions, the excitation-emission matrix (EEM) data for samples was simultaneously analyzed by multivariate curve resolution with alternating least squares (MCR-ALS) as a second-order standard addition method (SOSAM).}, } @article {pmid38457412, year = {2024}, author = {Nowicka, N and Zglejc-Waszak, K and Juranek, J and Korytko, A and Wąsowicz, K and Chmielewska-Krzesińska, M and Wojtkiewicz, J}, title = {Novel insights into RAGE signaling pathways during the progression of amyotrophic lateral sclerosis in RAGE-deficient SOD1 G93A mice.}, journal = {PloS one}, volume = {19}, number = {3}, pages = {e0299567}, pmid = {38457412}, issn = {1932-6203}, mesh = {Animals ; Humans ; Mice ; *Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology ; Disease Models, Animal ; Disease Progression ; Mice, Transgenic ; *Neurodegenerative Diseases ; Prospective Studies ; Receptor for Advanced Glycation End Products/genetics ; Signal Transduction ; Superoxide Dismutase/genetics/metabolism ; *Superoxide Dismutase-1/genetics/metabolism ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is neurodegenerative disease characterized by a progressive loss of motor neurons resulting in paralysis and muscle atrophy. One of the most prospective hypothesis on the ALS pathogenesis suggests that excessive inflammation and advanced glycation end-products (AGEs) accumulation play a crucial role in the development of ALS in patients and SOD1 G93A mice. Hence, we may speculate that RAGE, receptor for advanced glycation end-products and its proinflammatory ligands such as: HMGB1, S100B and CML contribute to ALS pathogenesis. The aim of our studies was to decipher the role of RAGE as well as provide insight into RAGE signaling pathways during the progression of ALS in SOD1 G93A and RAGE-deficient SOD1 G93A mice. In our study, we observed alternations in molecular pattern of proinflammatory RAGE ligands during progression of disease in RAGE KO SOD1 G93A mice compared to SOD1 G93A mice. Moreover, we observed that the amount of beta actin (ACTB) as well as Glial fibrillary acidic protein (GFAP) was elevated in SOD1 G93A mice when compared to mice with deletion of RAGE. These data contributes to our understanding of implications of RAGE and its ligands in pathogenesis of ALS and highlight potential targeted therapeutic interventions at the early stage of this devastating disease. Moreover, inhibition of the molecular cross-talk between RAGE and its proinflammatory ligands may abolish neuroinflammation, gliosis and motor neuron damage in SOD1 G93A mice. Hence, we hypothesize that attenuated interaction of RAGE with its proinflammatory ligands may improve well-being and health status during ALS in SOD1 G93A mice. Therefore, we emphasize that the inhibition of RAGE signaling pathway may be a therapeutic target for neurodegenerative diseases.}, } @article {pmid38457337, year = {2024}, author = {Fiore, APZP and Maity, S and Jeffery, L and An, D and Rendleman, J and Iannitelli, D and Choi, H and Mazzoni, E and Vogel, C}, title = {Identification of molecular signatures defines the differential proteostasis response in induced spinal and cranial motor neurons.}, journal = {Cell reports}, volume = {43}, number = {3}, pages = {113885}, pmid = {38457337}, issn = {2211-1247}, support = {R01 GM113237/GM/NIGMS NIH HHS/United States ; R35 GM127089/GM/NIGMS NIH HHS/United States ; }, mesh = {Humans ; *Proteostasis/physiology ; Proteome/metabolism ; Motor Neurons/metabolism ; *Amyotrophic Lateral Sclerosis/genetics ; Endoplasmic Reticulum/metabolism ; Endoplasmic Reticulum Stress ; }, abstract = {Amyotrophic lateral sclerosis damages proteostasis, affecting spinal and upper motor neurons earlier than a subset of cranial motor neurons. To aid disease understanding, we exposed induced cranial and spinal motor neurons (iCrMNs and iSpMNs) to proteotoxic stress, under which iCrMNs showed superior survival, quantifying the transcriptome and proteome for >8,200 genes at 0, 12, and 36 h. Two-thirds of the proteome showed cell-type differences. iSpMN-enriched proteins related to DNA/RNA metabolism, and iCrMN-enriched proteins acted in the endoplasmic reticulum (ER)/ER chaperone complex, tRNA aminoacylation, mitochondria, and the plasma/synaptic membrane, suggesting that iCrMNs expressed higher levels of proteins supporting proteostasis and neuronal function. When investigating the increased proteasome levels in iCrMNs, we showed that the activity of the 26S proteasome, but not of the 20S proteasome, was higher in iCrMNs than in iSpMNs, even after a stress-induced decrease. We identified Ublcp1 as an iCrMN-specific regulator of the nuclear 26S activity.}, } @article {pmid38456112, year = {2024}, author = {Saidi, NA and Abdul Karim, NS and Ismail, A and Raja Othman, RNF and Kasah, NHA and Yaakub, A and Ngoo, QZ}, title = {Does the Difference in Axial Length Affect the Refractive Outcome?.}, journal = {The Malaysian journal of medical sciences : MJMS}, volume = {31}, number = {1}, pages = {71-75}, pmid = {38456112}, issn = {1394-195X}, abstract = {BACKGROUND: The purpose of this study is to compare axial length (AL) and the refractive outcome after phacoemulsification surgery from 2014 to 2019 at Hospital Sultanah Nur Zahirah, Terengganu, Malaysia.

METHOD: This was a retrospective record review of all cataract patients who met the inclusion criteria and underwent uneventful superior wound phacoemulsification with nontoric intraocular lens (IOL) by a single surgeon from 2014 to 2019. Using optical biometry or immersion technique, the preoperative AL determined solely via the Sanders, Retzlaff and Kraff 2 (SRK2) formula was selected. The postoperative spherical equivalent (SE) at 6 weeks-12 weeks was retrieved. Using Statistical Package for the Social Sciences version 24.0, the mean differences between targeted and actual postoperative SE were analysed based on the AL.

RESULT: In this study, 490 eyes of 472 patients aged 25 years old-88 years old (mean age 65.72 years old [SD 8.83]) were involved. There were 162 eyes (33%) in Group A (< 23 mm), 189 eyes (39%) in Group B (23.01 mm-24.0 mm) and 139 eyes (28%) in Group C (> 24.0 mm). The mean AL was 23.63 mm (SD 1.19). The mean differences between the targeted and actual postoperative SE were: -0.09 D (SD 0.60) in Group A, -0.07 D (SD 0.53) in Group B and -0.16 D (SD 0.52) in Group C. No significant difference was found between these groups (P = 0.327).

CONCLUSION: There was no significant difference in the refractive outcome using the SRK2 formula in different ALs after phacoemulsification surgery. Hence, there is no reason to modify or adjust the targeted SE based on AL.}, } @article {pmid38455726, year = {2024}, author = {Liu, L and Wu, L and Li, Z and Fang, Y and Ju, B and Zhang, S and Bai, L and Pan, L}, title = {The Pro-197-Thr mutation in the ALS gene confers novel resistance patterns to ALS-inhibiting herbicides in Bromus japonicus in China.}, journal = {Frontiers in plant science}, volume = {15}, number = {}, pages = {1348815}, pmid = {38455726}, issn = {1664-462X}, abstract = {INTRODUCTION: Bromus japonicus is one of the most notorious agricultural weeds in China. The long-term use of ALS-inhibiting herbicides has led to rapid evolution of herbicide resistance in B. japonicus. B. japonicus population (BJ-R) surviving mesosulfuron-methyl treatment was collected from wheatland. Here, we aimed to confirm the resistance mechanisms in this putative resistant population.

METHODS: The dose-reponse tests were used to test the resistance level of the B. japonicus to ALS-inhibiting herbicides. Pretreatment with P450 and GST inhibitors and GST activity assays were used to determine whether P450 or GST was involved in the resistance of the BJ-R population. Sanger sequencing was used to analyse the ALS mutation of the BJ-R population. RT-qPCR was used to confirm the the expression levels of the ALS gene in mesosulfuron-methyl -resistant (BJ-R) and-susceptible (BJ-S) B. japonicus. An in vitro ALS activity assay was used to determine the ALS activity of the BJ-R and BJ-S populations. Homology modelling and docking were used to determine the binding energy of the BJ-R and BJ-S populations with ALS-inhibiting herbicides.

RESULTS: B. japonicus population (BJ-R) was confirmed to be 454- and 2.7-fold resistant to the SU herbicides mesosulfuron-methyl and nicosulfuron, and 7.3-, 2.3-, 1.1- and 10.8-fold resistant to the IMI herbicide imazamox, the TP herbicide penoxsulam, the PTB herbicide pyribenzoxim and the SCT herbicide flucarbazone-sodium, respectively, compared with its susceptible counterpart (BJ-S). Neither a P450 inhibitor nor a GST inhibitor could reverse the level of resistance to mesosulfuron-methyl in BJ-R. In addition, no significant differences in GST activity were found between the BJ-R and BJ-S. ALS gene sequencing revealed a Pro-197-Thr mutation in BJ-R, and the gene expression had no significant differences between the BJ-R and BJ-S. The ALS activity of BJ-R was 106-fold more tolerant to mesosulfuron-methyl than that of BJ-S. Molecular docking showed that the binding energy of the ALS active site and mesosulfuron-methyl was changed from -6.67 to -4.57 kcal mol[-1] due to the mutation at position 197.

DISCUSSION: These results suggested that the Pro-197-Thr mutation was the main reason for the high resistance level of BJ-R to mesosulfuron-methyl. Unlike previous reports of the cross-resistance pattern conferred by this mutation, we firstly documented that the Pro-197-Thr mutation confers broad cross-resistance spectrums to ALS-inhibiting herbicides in B. japonicus.}, } @article {pmid38452377, year = {2024}, author = {Rajabi, D and Khanmohammadi, S and Rezaei, N}, title = {The role of long noncoding RNAs in amyotrophic lateral sclerosis.}, journal = {Reviews in the neurosciences}, volume = {35}, number = {5}, pages = {533-547}, pmid = {38452377}, issn = {2191-0200}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics ; *RNA, Long Noncoding/genetics/metabolism ; Animals ; RNA-Binding Protein FUS/genetics ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease with a poor prognosis leading to death. The diagnosis and treatment of ALS are inherently challenging due to its complex pathomechanism. Long noncoding RNAs (lncRNAs) are transcripts longer than 200 nucleotides involved in different cellular processes, incisively gene expression. In recent years, more studies have been conducted on lncRNA classes and interference in different disease pathologies, showing their promising contribution to diagnosing and treating neurodegenerative diseases. In this review, we discussed the role of lncRNAs like NEAT1 and C9orf72-as in ALS pathogenesis mechanisms caused by mutations in different genes, including TAR DNA-binding protein-43 (TDP-43), fused in sarcoma (FUS), superoxide dismutase type 1 (SOD1). NEAT1 is a well-established lncRNA in ALS pathogenesis; hence, we elaborate on its involvement in forming paraspeckles, stress response, inflammatory response, and apoptosis. Furthermore, antisense lncRNAs (as-lncRNAs), a key group of transcripts from the opposite strand of genes, including ZEB1-AS1 and ATXN2-AS, are discussed as newly identified components in the pathology of ALS. Ultimately, we review the current standing of using lncRNAs as biomarkers and therapeutic agents and the future vision of further studies on lncRNA applications.}, } @article {pmid38451707, year = {2024}, author = {Clayton, EL and Huggon, L and Cousin, MA and Mizielinska, S}, title = {Synaptopathy: presynaptic convergence in frontotemporal dementia and amyotrophic lateral sclerosis.}, journal = {Brain : a journal of neurology}, volume = {147}, number = {7}, pages = {2289-2307}, pmid = {38451707}, issn = {1460-2156}, support = {P2003//Epilepsy Research UK/ ; /ALZS_/Alzheimer's Society/United Kingdom ; //UK Dementia Research Institute/ ; //UK Medical Research Council/ ; 529508//Simons Foundation/ ; 204954/Z/16/Z/WT_/Wellcome Trust/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; //Alzheimer's Research UK/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/pathology/physiopathology ; *Frontotemporal Dementia/genetics/pathology/physiopathology ; *Synapses/pathology ; *Presynaptic Terminals/pathology/metabolism ; Animals ; Mutation ; }, abstract = {Frontotemporal dementia and amyotrophic lateral sclerosis are common forms of neurodegenerative disease that share overlapping genetics and pathologies. Crucially, no significantly disease-modifying treatments are available for either disease. Identifying the earliest changes that initiate neuronal dysfunction is important for designing effective intervention therapeutics. The genes mutated in genetic forms of frontotemporal dementia and amyotrophic lateral sclerosis have diverse cellular functions, and multiple disease mechanisms have been proposed for both. Identification of a convergent disease mechanism in frontotemporal dementia and amyotrophic lateral sclerosis would focus research for a targetable pathway, which could potentially effectively treat all forms of frontotemporal dementia and amyotrophic lateral sclerosis (both familial and sporadic). Synaptopathies are diseases resulting from physiological dysfunction of synapses, and define the earliest stages in multiple neuronal diseases, with synapse loss a key feature in dementia. At the presynapse, the process of synaptic vesicle recruitment, fusion and recycling is necessary for activity-dependent neurotransmitter release. The unique distal location of the presynaptic terminal means the tight spatio-temporal control of presynaptic homeostasis is dependent on efficient local protein translation and degradation. Recently, numerous publications have shown that mutations associated with frontotemporal dementia and amyotrophic lateral sclerosis present with synaptopathy characterized by presynaptic dysfunction. This review will describe the complex local signalling and membrane trafficking events that occur at the presynapse to facilitate neurotransmission and will summarize recent publications linking frontotemporal dementia/amyotrophic lateral sclerosis genetic mutations to presynaptic function. This evidence indicates that presynaptic synaptopathy is an early and convergent event in frontotemporal dementia and amyotrophic lateral sclerosis and illustrates the need for further research in this area, to identify potential therapeutic targets with the ability to impact this convergent pathomechanism.}, } @article {pmid38450645, year = {2024}, author = {Roychowdhury, S and Joshi, D and Singh, VK and Faruq, M and Das, P}, title = {Genetic and in silico analysis of Indian sporadic young onset patient with amyotrophic lateral sclerosis.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {25}, number = {5-6}, pages = {589-599}, doi = {10.1080/21678421.2024.2324896}, pmid = {38450645}, issn = {2167-9223}, mesh = {Humans ; Age of Onset ; *Amyotrophic Lateral Sclerosis/genetics/epidemiology/diagnosis ; *Computer Simulation ; Exome Sequencing ; India/epidemiology ; Mutation, Missense/genetics ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is an old onset devastating neurodegenerative disorder. Young-onset ALS cases especially sporadic ones who are between 25 and 45 years are rarely affected by the disease. Despite the identification of numerous candidate genes associated with ALS, the etiology of the disease remains elusive due to extreme genetic and phenotypic variability. The advent of affordable whole exome sequencing (WES) has opened new avenues for unraveling the disease's pathophysiology better.

METHODS AND RESULTS: We aimed to determine the genetic basis of an Indian-origin, young onset sporadic ALS patient with very rapid deterioration of the disease course without any cognitive decline who was screened for mutations in major ALS candidate genes by WES. Variants detected were reconfirmed by Sanger sequencing. The clinicopathological features were investigated and two heterozygous missense variants were identified: R452W, not previously associated with ALS, present in one of the four conserved C terminal domains in ANXA11 and R208W in SIGMAR1, respectively. Both of these variants were predicted to be damaging by pathogenicity prediction tools and various in silico methods.

CONCLUSION: Our study revealed two potentially pathogenic variants in two ALS candidate genes. The genetic makeup of ALS patients from India has been the subject of a few prior studies, but none of them examined ANXA11 and SIGMAR1 genes so far. These results establish the framework for additional research into the pathogenic processes behind these variations that result in sporadic ALS disease and further our understanding of the genetic makeup of Indian ALS patients.}, } @article {pmid38448302, year = {2024}, author = {Heskamp, L and Birkbeck, MG and Hall, J and Schofield, IS and Bashford, J and Williams, TL and De Oliveira, HM and Whittaker, RG and Blamire, AM}, title = {Whole-body fasciculation detection in amyotrophic lateral sclerosis using motor unit MRI.}, journal = {Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology}, volume = {161}, number = {}, pages = {246-255}, doi = {10.1016/j.clinph.2024.02.016}, pmid = {38448302}, issn = {1872-8952}, support = {BASHFORD/JUN16/947-795/MNDA_/Motor Neurone Disease Association/United Kingdom ; MR/P000983/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology/diagnostic imaging ; Male ; Female ; Middle Aged ; *Fasciculation/physiopathology/diagnostic imaging ; *Magnetic Resonance Imaging/methods ; Aged ; *Electromyography/methods ; Muscle, Skeletal/physiopathology/diagnostic imaging ; Adult ; Motor Neurons/physiology ; Tongue/physiopathology/diagnostic imaging ; }, abstract = {OBJECTIVE: Compare fasciculation rates between amyotrophic lateral sclerosis (ALS) patients and healthy controls in body regions relevant for diagnosing ALS using motor unit MRI (MUMRI) at baseline and 6 months follow-up, and relate this to single-channel surface EMG (SEMG).

METHODS: Tongue, biceps brachii, paraspinals and lower legs were assessed with MUMRI and biceps brachii and soleus with SEMG in 10 healthy controls and 10 patients (9 typical ALS, 1 primary lateral sclerosis [PLS]).

RESULTS: MUMRI-detected fasciculation rates in typical ALS patients were higher compared to healthy controls for biceps brachii (2.40 ± 1.90 cm[-3]min[-1]vs. 0.04 ± 0.10 cm[-3]min[-1], p = 0.004), paraspinals (1.14 ± 1.61 cm[-3]min[-1]vs. 0.02 ± 0.02 cm[-3]min[-1], p = 0.016) and lower legs (1.42 ± 1.27 cm[-3]min[-1]vs. 0.13 ± 0.10 cm[-3]min[-1], p = 0.004), but not tongue (1.41 ± 1.94 cm[-3]min[-1]vs. 0.18 ± 0.18 cm[-3]min[-1], p = 0.556). The PLS patient showed no fasciculation. At baseline, 6/9 ALS patients had increased fasciculation rates compared to healthy controls in at least 2 body regions. At follow-up every patient had increased fasciculation rates in at least 2 body regions. The MUMRI-detected fasciculation rate correlated with SEMG-detected fasciculation rates (τ = 0.475, p = 0.006).

CONCLUSION: MUMRI can non-invasively image fasciculation in multiple body regions and appears sensitive to disease progression in individual patients.

SIGNIFICANCE: MUMRI has potential as diagnostic tool for ALS.}, } @article {pmid38447450, year = {2024}, author = {Malacarne, C and Giagnorio, E and Chirizzi, C and Cattaneo, M and Saraceno, F and Cavalcante, P and Bonanno, S and Mantegazza, R and Moreno-Manzano, V and Lauria, G and Metrangolo, P and Bombelli, FB and Marcuzzo, S}, title = {FM19G11-loaded nanoparticles modulate energetic status and production of reactive oxygen species in myoblasts from ALS mice.}, journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie}, volume = {173}, number = {}, pages = {116380}, doi = {10.1016/j.biopha.2024.116380}, pmid = {38447450}, issn = {1950-6007}, mesh = {Mice ; Animals ; Superoxide Dismutase-1/metabolism ; Reactive Oxygen Species/metabolism ; *Amyotrophic Lateral Sclerosis/drug therapy ; *Neurodegenerative Diseases/pathology ; Myoblasts/metabolism ; *Nanoparticles ; Atrophy/pathology ; Mice, Transgenic ; Disease Models, Animal ; Superoxide Dismutase/metabolism ; *Benzamides ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease affecting motor neurons. Considerable evidence indicates that early skeletal muscle atrophy plays a crucial role in the disease pathogenesis, leading to an altered muscle-motor neuron crosstalk that, in turn, may contribute to motor neuron degeneration. Currently, there is no effective treatment for ALS, highlighting the need to dig deeper into the pathological mechanisms for developing innovative therapeutic strategies. FM19G11 is a novel drug able to modulate the global cellular metabolism, but its effects on ALS skeletal muscle atrophy and mitochondrial metabolism have never been evaluated, yet. This study investigated whether FM19G11-loaded nanoparticles (NPs) may affect the bioenergetic status in myoblasts isolated from G93A-SOD1 mice at different disease stages. We found that FM19G1-loaded NP treatment was able to increase transcriptional levels of Akt1, Akt3, Mef2a, Mef2c and Ucp2, which are key genes associated with cell proliferation (Akt1, Akt3), muscle differentiation (Mef2c), and mitochondrial activity (Ucp2), in G93A-SOD1 myoblasts. These cells also showed a significant reduction of mitochondrial area and networks, in addition to decreased ROS production after treatment with FM19G11-loaded NPs, suggesting a ROS clearance upon the amelioration of mitochondrial dynamics. Our overall findings demonstrate a significant impact of FM19G11-loaded NPs on muscle cell function and bioenergetic status in G93A-SOD1 myoblasts, thus promising to open new avenues towards possible adoption of FM19G11-based nanotherapies to slow muscle degeneration in the frame of ALS and muscle disorders.}, } @article {pmid38446760, year = {2024}, author = {Unni, S and Kommu, P and Aouti, S and Nalli, Y and Bharath, MMS and Ali, A and Padmanabhan, B}, title = {Structural insights into the modulation Of SOD1 aggregation By a fungal metabolite Phialomustin-B: Therapeutic potential in ALS.}, journal = {PloS one}, volume = {19}, number = {3}, pages = {e0298196}, pmid = {38446760}, issn = {1932-6203}, mesh = {Humans ; Superoxide Dismutase-1/genetics ; *Amyotrophic Lateral Sclerosis/drug therapy/genetics ; Cytoskeleton ; Muscular Atrophy ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal human motor neuron disease leading to muscle atrophy and paralysis. Mutations in superoxide dismutase 1 (SOD1) are associated with familial ALS (fALS). The SOD1 mutants in ALS have a toxic-gain of function by destabilizing the functional SOD1 homodimer, consequently inducing fibril-like aggregation with a cytotoxic non-native trimer intermediate. Therefore, reducing SOD1 oligomerization via chemical modulators is an optimal therapy in ALS. Here, we report the discovery of Phialomustin-B, an unsaturated secondary metabolite from the endophytic fungus Phialophora mustea, as a modulator of SOD1 aggregation. The crystal structure of the SOD1-Phialomustin complex refined to 1.90 Å resolution demonstrated for the first time that the ligand binds to the dimer interface and the lateral region near the electrostatic loop. The aggregation analyses of SOD1WT and the disease mutant SOD1A4V revealed that Phialomustin-B reduces cytotoxic trimerization. We propose that Phialomustin-B is a potent lead molecule with therapeutic potential in fALS.}, } @article {pmid38445369, year = {2024}, author = {Nishimura, K and Sanchez-Molano, J and Kerr, N and Pressman, Y and Silvera, R and Khan, A and Gajavelli, S and Bramlett, HM and Dietrich, WD}, title = {Beneficial Effects of Human Schwann Cell-Derived Exosomes in Mitigating Secondary Damage After Penetrating Ballistic-Like Brain Injury.}, journal = {Journal of neurotrauma}, volume = {41}, number = {21-22}, pages = {2395-2412}, pmid = {38445369}, issn = {1557-9042}, support = {R37 NS133195/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; *Rats, Sprague-Dawley ; Male ; Rats ; *Exosomes/metabolism/transplantation ; Humans ; *Schwann Cells/metabolism ; *Head Injuries, Penetrating ; }, abstract = {There is a growing body of evidence that the delivery of cell-derived exosomes normally involved in intracellular communication can reduce secondary injury mechanisms after brain and spinal cord injury and improve outcomes. Exosomes are nanometer-sized vesicles that are released by Schwann cells and may have neuroprotective effects by reducing post-traumatic inflammatory processes as well as promoting tissue healing and functional recovery. The purpose of this study was to evaluate the beneficial effects of human Schwann-cell exosomes (hSC-Exos) in a severe model of penetrating ballistic-like brain injury (PBBI) in rats and investigate effects on multiple outcomes. Human Schwann cell processing protocols followed Current Good Manufacturing Practices (cGMP) with exosome extraction and purification steps approved by the Food and Drug Administration for an expanded access single ALS patient Investigational New Drug. Anesthetized male Sprague-Dawley rats (280-350g) underwent PBBI surgery or Sham procedures and, starting 30 min after injury, received either a dose of hSC-Exos or phosphate-buffered saline through the jugular vein. At 48h after PBBI, flow cytometry analysis of cortical tissue revealed that hSC-Exos administration reduced the number of activated microglia and levels of caspase-1, a marker of inflammasome activation. Neuropathological analysis at 21 days showed that hSC-Exos treatment after PBBI significantly reduced overall contusion volume and decreased the frequency of Iba-1 positive activated and amoeboid microglia by immunocytochemical analysis. This study revealed that the systemic administration of hSC-Exos is neuroprotective in a model of severe TBI and reduces secondary inflammatory injury mechanisms and histopathological damage. The administration of hSC-Exos represents a clinically relevant cell-based therapy to limit the detrimental effects of neurotrauma or other progressive neurological injuries by impacting multiple pathophysiological events and promoting neurological recovery.}, } @article {pmid38445096, year = {2024}, author = {Shabber, SM and Sumesh, EP}, title = {AFM signal model for dysarthric speech classification using speech biomarkers.}, journal = {Frontiers in human neuroscience}, volume = {18}, number = {}, pages = {1346297}, pmid = {38445096}, issn = {1662-5161}, abstract = {Neurological disorders include various conditions affecting the brain, spinal cord, and nervous system which results in reduced performance in different organs and muscles throughout the human body. Dysarthia is a neurological disorder that significantly impairs an individual's ability to effectively communicate through speech. Individuals with dysarthria are characterized by muscle weakness that results in slow, slurred, and less intelligible speech production. An efficient identification of speech disorders at the beginning stages helps doctors suggest proper medications. The classification of dysarthric speech assumes a pivotal role as a diagnostic tool, enabling accurate differentiation between healthy speech patterns and those affected by dysarthria. Achieving a clear distinction between dysarthric speech and the speech of healthy individuals is made possible through the application of advanced machine learning techniques. In this work, we conducted feature extraction by utilizing the Amplitude and frequency modulated (AFM) signal model, resulting in the generation of a comprehensive array of unique features. A method involving Fourier-Bessel series expansion is employed to separate various components within a complex speech signal into distinct elements. Subsequently, the Discrete Energy Separation Algorithm is utilized to extract essential parameters, namely the Amplitude envelope and Instantaneous frequency, from each component within the speech signal. To ensure the robustness and applicability of our findings, we harnessed data from various sources, including TORGO, UA Speech, and Parkinson datasets. Furthermore, the classifier's performance was evaluated based on multiple measures such as the area under the curve, F1-Score, sensitivity, and accuracy, encompassing KNN, SVM, LDA, NB, and Boosted Tree. Our analyses resulted in classification accuracies ranging from 85 to 97.8% and the F1-score ranging between 0.90 and 0.97.}, } @article {pmid38444607, year = {2024}, author = {Uozumi, R and Mori, K and Gotoh, S and Miyamoto, T and Kondo, S and Yamashita, T and Kawabe, Y and Tagami, S and Akamine, S and Ikeda, M}, title = {PABPC1 mediates degradation of C9orf72-FTLD/ALS GGGGCC repeat RNA.}, journal = {iScience}, volume = {27}, number = {3}, pages = {109303}, pmid = {38444607}, issn = {2589-0042}, abstract = {GGGGCC hexanucleotide repeat expansion in C9orf72 causes frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Expanded GGGGCC repeat RNA accumulates within RNA foci and is translated into toxic dipeptide repeat proteins; thus, efficient repeat RNA degradation may alleviate diseases. hnRNPA3, one of the repeat RNA-binding proteins, has been implicated in the destabilization of repeat RNA. Using APEX2-mediated proximity biotinylation, here, we demonstrate PABPC1, a cytoplasmic poly (A)-binding protein, interacts with hnRNPA3. Knockdown of PABPC1 increased the accumulation of repeat RNA and RNA foci to the same extent as the knockdown of hnRNPA3. Proximity ligation assays indicated PABPC1-hnRNPA3 and PABPC1-RNA exosomes, a complex that degrades repeat RNA, preferentially co-localized when repeat RNA was present. Our results suggest that PABPC1 functions as a mediator of polyadenylated GGGGCC repeat RNA degradation through interactions with hnRNPA3 and RNA exosome complex.}, } @article {pmid38443977, year = {2024}, author = {Duan, QQ and Wang, H and Su, WM and Gu, XJ and Shen, XF and Jiang, Z and Ren, YL and Cao, B and Li, GB and Wang, Y and Chen, YP}, title = {TBK1, a prioritized drug repurposing target for amyotrophic lateral sclerosis: evidence from druggable genome Mendelian randomization and pharmacological verification in vitro.}, journal = {BMC medicine}, volume = {22}, number = {1}, pages = {96}, pmid = {38443977}, issn = {1741-7015}, support = {2022YFC2703101//the National Key Research and Development Program of China/ ; 2021YFS0051//Sichuan Province Science and Technology Support Program/ ; 2023YFS0269//Sichuan Province Science and Technology Support Program/ ; 81971188//the National Natural Science Fund of China/ ; 2022NSFSC0749//the National Natural Science Fund of Sichuan/ ; 2023HXFH032//the 1·3·5 project for disciplines of excellence Clinical Research Fund, West China Hospital, Sichuan University/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy/genetics ; Drug Repositioning ; Mendelian Randomization Analysis ; Protein Serine-Threonine Kinases/genetics ; *Aminopyridines ; }, abstract = {BACKGROUND: There is a lack of effective therapeutic strategies for amyotrophic lateral sclerosis (ALS); therefore, drug repurposing might provide a rapid approach to meet the urgent need for treatment.

METHODS: To identify therapeutic targets associated with ALS, we conducted Mendelian randomization (MR) analysis and colocalization analysis using cis-eQTL of druggable gene and ALS GWAS data collections to determine annotated druggable gene targets that exhibited significant associations with ALS. By subsequent repurposing drug discovery coupled with inclusion criteria selection, we identified several drug candidates corresponding to their druggable gene targets that have been genetically validated. The pharmacological assays were then conducted to further assess the efficacy of genetics-supported repurposed drugs for potential ALS therapy in various cellular models.

RESULTS: Through MR analysis, we identified potential ALS druggable genes in the blood, including TBK1 [OR 1.30, 95%CI (1.19, 1.42)], TNFSF12 [OR 1.36, 95%CI (1.19, 1.56)], GPX3 [OR 1.28, 95%CI (1.15, 1.43)], TNFSF13 [OR 0.45, 95%CI (0.32, 0.64)], and CD68 [OR 0.38, 95%CI (0.24, 0.58)]. Additionally, we identified potential ALS druggable genes in the brain, including RESP18 [OR 1.11, 95%CI (1.07, 1.16)], GPX3 [OR 0.57, 95%CI (0.48, 0.68)], GDF9 [OR 0.77, 95%CI (0.67, 0.88)], and PTPRN [OR 0.17, 95%CI (0.08, 0.34)]. Among them, TBK1, TNFSF12, RESP18, and GPX3 were confirmed in further colocalization analysis. We identified five drugs with repurposing opportunities targeting TBK1, TNFSF12, and GPX3, namely fostamatinib (R788), amlexanox (AMX), BIIB-023, RG-7212, and glutathione as potential repurposing drugs. R788 and AMX were prioritized due to their genetic supports, safety profiles, and cost-effectiveness evaluation. Further pharmacological analysis revealed that R788 and AMX mitigated neuroinflammation in ALS cell models characterized by overly active cGAS/STING signaling that was induced by MSA-2 or ALS-related toxic proteins (TDP-43 and SOD1), through the inhibition of TBK1 phosphorylation.

CONCLUSIONS: Our MR analyses provided genetic evidence supporting TBK1, TNFSF12, RESP18, and GPX3 as druggable genes for ALS treatment. Among the drug candidates targeting the above genes with repurposing opportunities, FDA-approved drug-R788 and AMX served as effective TBK1 inhibitors. The subsequent pharmacological studies validated the potential of R788 and AMX for treating specific ALS subtypes through the inhibition of TBK1 phosphorylation.}, } @article {pmid38443601, year = {2024}, author = {Spence, H and Waldron, FM and Saleeb, RS and Brown, AL and Rifai, OM and Gilodi, M and Read, F and Roberts, K and Milne, G and Wilkinson, D and O'Shaughnessy, J and Pastore, A and Fratta, P and Shneider, N and Tartaglia, GG and Zacco, E and Horrocks, MH and Gregory, JM}, title = {RNA aptamer reveals nuclear TDP-43 pathology is an early aggregation event that coincides with STMN-2 cryptic splicing and precedes clinical manifestation in ALS.}, journal = {Acta neuropathologica}, volume = {147}, number = {1}, pages = {50}, pmid = {38443601}, issn = {1432-0533}, support = {MR/S006508/1/MRC_/Medical Research Council/United Kingdom ; R01 NS127186/NS/NINDS NIH HHS/United States ; R01NS127186/GF/NIH HHS/United States ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics ; *Aptamers, Nucleotide ; DNA-Binding Proteins/genetics ; RNA Splicing ; Antibodies ; }, abstract = {TDP-43 is an aggregation-prone protein which accumulates in the hallmark pathological inclusions of amyotrophic lateral sclerosis (ALS). However, the analysis of deeply phenotyped human post-mortem samples has shown that TDP-43 aggregation, revealed by standard antibody methods, correlates poorly with symptom manifestation. Recent identification of cryptic-splicing events, such as the detection of Stathmin-2 (STMN-2) cryptic exons, are providing evidence implicating TDP-43 loss-of-function as a potential driving pathomechanism but the temporal nature of TDP-43 loss and its relation to the disease process and clinical phenotype is not known. To address these outstanding questions, we used a novel RNA aptamer, TDP-43[APT], to detect TDP-43 pathology and used single molecule in situ hybridization to sensitively reveal TDP-43 loss-of-function and applied these in a deeply phenotyped human post-mortem tissue cohort. We demonstrate that TDP-43[APT] identifies pathological TDP-43, detecting aggregation events that cannot be detected by classical antibody stains. We show that nuclear TDP-43 pathology is an early event, occurring prior to cytoplasmic accumulation and is associated with loss-of-function measured by coincident STMN-2 cryptic splicing pathology. Crucially, we show that these pathological features of TDP-43 loss-of-function precede the clinical inflection point and are not required for region specific clinical manifestation. Furthermore, we demonstrate that gain-of-function in the form of extensive cytoplasmic accumulation, but not loss-of-function, is the primary molecular correlate of clinical manifestation. Taken together, our findings demonstrate implications for early diagnostics as the presence of STMN-2 cryptic exons and early TDP-43 aggregation events could be detected prior to symptom onset, holding promise for early intervention in ALS.}, } @article {pmid38443479, year = {2024}, author = {Fyfe, I}, title = {α-Synuclein seeds in amyotrophic lateral sclerosis.}, journal = {Nature reviews. Neurology}, volume = {20}, number = {4}, pages = {203}, pmid = {38443479}, issn = {1759-4766}, mesh = {Humans ; *alpha-Synuclein ; *Amyotrophic Lateral Sclerosis ; }, } @article {pmid38441935, year = {2024}, author = {Finsterer, J}, title = {Whether Clenbuterol Is Beneficial in Sporadic ALS Can Only Be Answered Through Appropriately Designed Studies.}, journal = {Journal of clinical neuromuscular disease}, volume = {25}, number = {3}, pages = {150-151}, doi = {10.1097/CND.0000000000000475}, pmid = {38441935}, issn = {1537-1611}, mesh = {Humans ; *Clenbuterol/therapeutic use ; *Amyotrophic Lateral Sclerosis/drug therapy ; }, } @article {pmid38441932, year = {2024}, author = {Gomathy, SB and Das, A and Srivastava, AK}, title = {Flail Leg Phenotype in Familial Amyotrophic Lateral Sclerosis: Think of a Cause With Something to Offer.}, journal = {Journal of clinical neuromuscular disease}, volume = {25}, number = {3}, pages = {144-145}, doi = {10.1097/CND.0000000000000471}, pmid = {38441932}, issn = {1537-1611}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/complications/genetics ; Leg ; }, } @article {pmid38435594, year = {2024}, author = {Wei, J and Yan, H and Shao, X and Zhao, L and Han, L and Yan, P and Wang, S}, title = {A machine learning-based hybrid recommender framework for smart medical systems.}, journal = {PeerJ. Computer science}, volume = {10}, number = {}, pages = {e1880}, pmid = {38435594}, issn = {2376-5992}, abstract = {This article presents a hybrid recommender framework for smart medical systems by introducing two methods to improve service level evaluations and doctor recommendations for patients. The first method uses big data techniques and deep learning algorithms to develop a registration review system in medical institutions. This system outperforms conventional evaluation methods, thus achieving higher accuracy. The second method implements the term frequency and inverse document frequency (TF-IDF) algorithm to construct a model based on the patient's symptom vector space, incorporating score weighting, modified cosine similarity, and K-means clustering. Then, the alternating least squares (ALS) matrix decomposition and user collaborative filtering algorithm are applied to calculate patients' predicted scores for doctors and recommend top-performing doctors. Experimental results show significant improvements in metrics called precision and recall rates compared to conventional methods, making the proposed approach a practical solution for department triage and doctor recommendation in medical appointment platforms.}, } @article {pmid38435120, year = {2024}, author = {Duan, C and Kang, M and Pan, X and Gan, Z and Huang, V and Li, G and Place, RF and Li, LC}, title = {Intrathecal administration of a novel siRNA modality extends survival and improves motor function in the SOD1[G93A] ALS mouse model.}, journal = {Molecular therapy. Nucleic acids}, volume = {35}, number = {1}, pages = {102147}, pmid = {38435120}, issn = {2162-2531}, abstract = {Antisense oligonucleotides (ASOs) were the first modality to pioneer targeted gene knockdown in the treatment of amyotrophic lateral sclerosis (ALS) caused by mutant superoxide dismutase 1 (SOD1). RNA interference (RNAi) is another mechanism of gene silencing in which short interfering RNAs (siRNAs) effectively degrade complementary transcripts. However, delivery to extrahepatic tissues like the CNS has been a bottleneck in the clinical development of RNAi. Herein, we identify potent siRNA duplexes for the knockdown of human SOD1 in which medicinal chemistry and conjugation to an accessory oligonucleotide (ACO) enable activity in CNS tissues. Local delivery via intracerebroventricular or intrathecal injection into SOD1[G93A] mice delayed disease progression and extended animal survival with superior efficacy compared with an ASO resembling tofersen in sequence and chemistry. Treatment also prevented disease-related declines in motor function, including improvements in animal mobility, muscle strength, and coordination. The ACO itself does not target any specific complementary nucleic acid sequence; rather, it imparts benefits conducive to bioavailability and delivery through its chemistry. The complete conjugate (i.e., siRNA-ACO) represents a novel modality for delivery of duplex RNA (e.g., siRNA) to the CNS that is currently being tested in the clinic for treatment of ALS.}, } @article {pmid38435055, year = {2024}, author = {Peterson, IL and Thompson, AD and Scholpa, NE and Largent-Milnes, T and Schnellmann, RG}, title = {Isolation and monoculture of functional primary astrocytes from the adult mouse spinal cord.}, journal = {Frontiers in neuroscience}, volume = {18}, number = {}, pages = {1367473}, pmid = {38435055}, issn = {1662-4548}, support = {T32 ES007091/ES/NIEHS NIH HHS/United States ; P30 ES006694/ES/NIEHS NIH HHS/United States ; IK2 BX005218/BX/BLRD VA/United States ; I01 BX004868/BX/BLRD VA/United States ; T32 HL007249/HL/NHLBI NIH HHS/United States ; R01 NS126752/NS/NINDS NIH HHS/United States ; }, abstract = {Astrocytes are a widely heterogenic cell population that play major roles in central nervous system (CNS) homeostasis and neurotransmission, as well as in various neuropathologies, including spinal cord injury (SCI), traumatic brain injury, and neurodegenerative diseases, such as amyotrophic lateral sclerosis. Spinal cord astrocytes have distinct differences from those in the brain and accurate modeling of disease states is necessary for understanding disease progression and developing therapeutic interventions. Several limitations to modeling spinal cord astrocytes in vitro exist, including lack of commercially available adult-derived cells, lack of purchasable astrocytes with different genotypes, as well as time-consuming and costly in-house primary cell isolations that often result in low yield due to small tissue volume. To address these issues, we developed an efficient adult mouse spinal cord astrocyte isolation method that utilizes enzymatic digestion, debris filtration, and multiple ACSA-2 magnetic microbead purification cycles to achieve an astrocyte monoculture purity of ≅93-98%, based on all markers assessed. Importantly, the isolated cells contain active mitochondria and express key astrocyte markers including ACSA-1, ACSA-2, EAAT2, and GFAP. Furthermore, this isolation method can be applied to the spinal cord of male and female mice, mice subjected to SCI, and genetically modified mice. We present a primary adult mouse spinal cord astrocyte isolation protocol focused on purity, viability, and length of isolation that can be applied to a multitude of models and aid in targeted research on spinal-cord related CNS processes and pathologies.}, } @article {pmid38434715, year = {2024}, author = {Kumar, R and Blackband, J and Wagle Shukla, A}, title = {Rhythmic Jaw Movements in Amyotrophic Lateral Sclerosis: Is It Clonus or Tremor?.}, journal = {Tremor and other hyperkinetic movements (New York, N.Y.)}, volume = {14}, number = {}, pages = {8}, pmid = {38434715}, issn = {2160-8288}, mesh = {Humans ; Tremor/etiology ; *Essential Tremor/diagnosis ; *Parkinson Disease ; *Amyotrophic Lateral Sclerosis/complications ; Movement ; Reflex, Abnormal ; }, abstract = {BACKGROUND: Jaw clonus refers to involuntary, rhythmic jaw contractions induced by a hyperactive trigeminal nerve stretch reflex; however, the movements, when triggered without a stretch, can be confused with a tremor.

PHENOMENOLOGY SHOWN: This video demonstrates a patient with amyotrophic lateral sclerosis presenting with rapid rhythmic jaw movements seen at rest, alongside a power spectrum analysis revealing a narrow high-frequency peak of 10 Hz.

EDUCATIONAL VALUE: Rhythmic jaw movements are seen in many disorders such as Parkinson's disease, essential tremor, tardive syndromes, and cranial myorhythmias; however, a high-frequency movement, regardless of clonus or tremor, can indicate amyotrophic lateral sclerosis when accompanied by typical upper and lower motor neuron signs.

HIGHLIGHTS: The presented video abstract shows a patient with amyotrophic lateral sclerosis with rhythmic jaw movements seen at rest. A power spectrum analysis of the rhythmic movements revealed a 10 Hz peak, a frequency higher than those seen in patients with Parkinson's disease, essential tremor, myorhythmia, and tardive syndromes.}, } @article {pmid38433895, year = {2024}, author = {Lépine, S and Nauleau-Javaudin, A and Deneault, E and Chen, CX and Abdian, N and Franco-Flores, AK and Haghi, G and Castellanos-Montiel, MJ and Maussion, G and Chaineau, M and Durcan, TM}, title = {Homozygous ALS-linked mutations in TARDBP/TDP-43 lead to hypoactivity and synaptic abnormalities in human iPSC-derived motor neurons.}, journal = {iScience}, volume = {27}, number = {3}, pages = {109166}, pmid = {38433895}, issn = {2589-0042}, abstract = {Cytoplasmic mislocalization and aggregation of the RNA-binding protein TDP-43 is a pathological hallmark of the motor neuron (MN) disease amyotrophic lateral sclerosis (ALS). Furthermore, while mutations in TARDBP (encoding TDP-43) have been associated with ALS, the pathogenic consequences of these mutations remain poorly understood. Using CRISPR-Cas9, we engineered two homozygous knock-in induced pluripotent stem cell lines carrying mutations in TARDBP encoding TDP-43[A382T] and TDP-43[G348C], two common yet understudied ALS TDP-43 variants. Motor neurons (MNs) differentiated from knock-in iPSCs had normal viability and displayed no significant changes in TDP-43 subcellular localization, phosphorylation, solubility, or aggregation compared with isogenic control MNs. However, our results highlight synaptic impairments in both TDP-43[A382T] and TDP-43[G348C] MN cultures, as reflected in synapse abnormalities and alterations in spontaneous neuronal activity. Collectively, our findings suggest that MN dysfunction may precede the occurrence of TDP-43 pathology and neurodegeneration in ALS and further implicate synaptic and excitability defects in the pathobiology of this disease.}, } @article {pmid38432083, year = {2024}, author = {Straczkiewicz, M and Karas, M and Johnson, SA and Burke, KM and Scheier, Z and Royse, TB and Calcagno, N and Clark, A and Iyer, A and Berry, JD and Onnela, JP}, title = {Upper limb movements as digital biomarkers in people with ALS.}, journal = {EBioMedicine}, volume = {101}, number = {}, pages = {105036}, pmid = {38432083}, issn = {2352-3964}, support = {U01 HL145386/HL/NHLBI NIH HHS/United States ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis ; Upper Extremity ; Wrist ; Disease Progression ; Biomarkers ; }, abstract = {BACKGROUND: Objective evaluation of people with amyotrophic lateral sclerosis (PALS) in free-living settings is challenging. The introduction of portable digital devices, such as wearables and smartphones, may improve quantifying disease progression and hasten therapeutic development. However, there is a need for tools to characterize upper limb movements in neurologic disease and disability.

METHODS: Twenty PALS wore a wearable accelerometer, ActiGraph Insight Watch, on their wrist for six months. They also used Beiwe, a smartphone application that collected self-entry ALS Functional Rating Scale-Revised (ALSFRS-RSE) survey responses every 1-4 weeks. We developed several measures that quantify count and duration of upper limb movements: flexion, extension, supination, and pronation. New measures were compared against ALSFRS-RSE total score (Q1-12), and individual responses to specific questions related to handwriting (Q4), cutting food (Q5), dressing and performing hygiene (Q6), and turning in bed and adjusting bed clothes (Q7). Additional analysis considered adjusting for total activity counts (TAC).

FINDINGS: At baseline, PALS with higher Q1-12 performed more upper limb movements, and these movements were faster compared to individuals with more advanced disease. Most upper limb movement metrics had statistically significant change over time, indicating declining function either by decreasing count metrics or by increasing duration metric. All count and duration metrics were significantly associated with Q1-12, flexion and extension counts were significantly associated with Q6 and Q7, supination and pronation counts were also associated with Q4. All duration metrics were associated with Q6 and Q7. All duration metrics retained their statistical significance after adjusting for TAC.

INTERPRETATION: Wearable accelerometer data can be used to generate digital biomarkers on upper limb movements and facilitate patient monitoring in free-living environments. The presented method offers interpretable monitoring of patients' functioning and versatile tracking of disease progression in the limb of interest.

FUNDING: Mitsubishi-Tanabe Pharma Holdings America, Inc.}, } @article {pmid38432041, year = {2024}, author = {Yu, W and Wang, H and Li, M and Yang, F and Bai, J and Song, H and Huang, X}, title = {Prognostic value of geriatric nutritional risk index in patients with amyotrophic lateral sclerosis.}, journal = {Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia}, volume = {122}, number = {}, pages = {19-24}, doi = {10.1016/j.jocn.2024.02.011}, pmid = {38432041}, issn = {1532-2653}, mesh = {Humans ; Aged ; Prognosis ; *Amyotrophic Lateral Sclerosis/complications/diagnosis ; Delayed Diagnosis ; Nutritional Status ; Disease Progression ; Risk Factors ; Retrospective Studies ; }, abstract = {BACKGROUND: The geriatric nutritional risk index (GNRI) is a prognostic indicator for several diseases, meanwhile, nutrition and inflammation play important roles in the disease progression of amyotrophic lateral sclerosis (ALS). However, the association between the GNRI and ALS remains unknown.

METHODS: 443 patients diagnosed with ALS were divided into two groups based on the GNRI levels. Associations between GNRI and survival time were analyzed using Kaplan-Meier curves and compared by the log-rank test. Univariate and multivariate analyses were used to assess their prognostic values for survival time. Spearman correlation analysis was used to evaluate the correlation coefficients between GNRI and other clinical variables.

RESULTS: No significant differences were found in diagnostic delay between the two groups. The onset age and disease progression rate (DPR) were significantly lower in high GNRI group while forced vital capacity (FVC), revised version of the ALS functional rating scale (ALSFRS-R), serum albumin and body mass index (BMI) were significantly lower in low GNRI group. Lower GNRI levels were linked with shorter ALS patients' survival time by Kaplan-Meier curves. The univariate and multivariate analysis identified the onset age, gender, onset site, diagnostic delay, DRP and GNRI as predictors of survival time in patients with ALS.

CONCLUSION: Nutritional status was closely corelated with ALS progression. The GNRI may be used as a potential prognostic indictor for ALS patients.}, } @article {pmid38431841, year = {2024}, author = {Gao, C and Shi, Q and Pan, X and Chen, J and Zhang, Y and Lang, J and Wen, S and Liu, X and Cheng, TL and Lei, K}, title = {Neuromuscular organoids model spinal neuromuscular pathologies in C9orf72 amyotrophic lateral sclerosis.}, journal = {Cell reports}, volume = {43}, number = {3}, pages = {113892}, doi = {10.1016/j.celrep.2024.113892}, pmid = {38431841}, issn = {2211-1247}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/pathology ; C9orf72 Protein/genetics/metabolism ; *Frontotemporal Dementia/genetics/pathology ; Proteins/genetics ; Dipeptides/pharmacology/metabolism ; DNA Repeat Expansion ; }, abstract = {Hexanucleotide repeat expansions in the C9orf72 gene are the most common cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. Due to the lack of trunk neuromuscular organoids (NMOs) from ALS patients' induced pluripotent stem cells (iPSCs), an organoid system was missing to model the trunk spinal neuromuscular neurodegeneration. With the C9orf72 ALS patient-derived iPSCs and isogenic controls, we used an NMO system containing trunk spinal cord neural and peripheral muscular tissues to show that the ALS NMOs could model peripheral defects in ALS, including contraction weakness, neural denervation, and loss of Schwann cells. The neurons and astrocytes in ALS NMOs manifested the RNA foci and dipeptide repeat proteins. Acute treatment with the unfolded protein response inhibitor GSK2606414 increased the glutamatergic muscular contraction 2-fold and reduced the dipeptide repeat protein aggregation and autophagy. This study provides an organoid system for spinal neuromuscular pathologies in ALS and its application for drug testing.}, } @article {pmid38431830, year = {2024}, author = {Li, R and Han, X and Wang, Q and Wang, C and Jing, W and Zhang, H and Wang, J and Pan, W}, title = {Network pharmacology analysis and clinical efficacy of the traditional Chinese medicine Bu-Shen-Jian-Pi. Part 3: Alleviation of hypoxia, muscle-wasting, and modulation of redox functions in amyotrophic lateral sclerosis.}, journal = {International journal of clinical pharmacology and therapeutics}, volume = {62}, number = {4}, pages = {169-177}, doi = {10.5414/CP204520}, pmid = {38431830}, issn = {0946-1965}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy/diagnosis ; Medicine, Chinese Traditional ; Network Pharmacology ; Treatment Outcome ; Hypoxia ; Cholecalciferol ; Muscles ; Disease Progression ; }, abstract = {OBJECTIVE: The aim of this clinical study is to obtain evidence for the clinical efficacy of Bu-Shen-Jian-Pi formula (BSJP), a traditional Chinese medicine, used for the treatment of amyotrophic lateral sclerosis, a relatively rare, progressive and usually fatal disease possibly associated with alterations in tissue redox status, hypoxia, and muscular injury.

BACKGROUND: The active agents in BSJP formula[†] causing apoptosis, modulation of redox changes, and alterations in the immune status have been studied previously by us using cell cultures. The findings from these investigations have been incorporated into pharmacology databases employed in our analysis of BSJP using network pharmacology analysis/artifical intelligence. This information has been used here in the design of the investigation and to optimize evaluation of the clinical efficacy and usefulness of this herbal medicine, as far as possible using evidence-based medicine criteria.

MATERIALS AND METHODS: The design of the study was a randomized multi-center, controlled clinical trial in 127 patients with confirmed diagnoses of amyotrophic lateral sclerosis. Patients and investigator were double-blinded. Clinical efficacy was determined using the Amyotrophic Lateral Sclerosis Symptom Score in Integrative Treatment Scale (ALS-SSIT) and the Amyotrophic Lateral Sclerosis Rating Scale-Revised (ALSFRS-R), together with tests of limb muscle strength using the manual muscle test (MMT), forced vital capacity (FVC), and clinical chemistry laboratory tests over a 20-week observation period.

RESULTS: The scores of ALS-SSIT in the BSJP group increased significantly (22%) after treatment. The ALSFRS-R score in the BSJP group decreased significantly after treatment (19%). The rate of decrease in muscle function (MMT score) in most BSJP patients was lower than that in the control group, where the differences in the scores for the trapezius and triceps brachii were statistically significant compared to the control group. The fall in FVC in the BJSP group was significantly slower than in the control group. There were no marked differences observed in the frequency of side effects. Serum vitamin D3 levels in the BSJP group showed greater increases compared to the control group.

CONCLUSION: BSJP treatment reduced the rate of progression of amyotrophic lateral sclerosis according to the ALS-SSITS and ALSFRS scores and significantly reduced the rate of deterioration in muscle function in the limbs of amyotrophic lateral sclerosis patients. The modes of action of BSJP in treating amyotrophic lateral sclerosis are probably diverse and multi targeted, some of which may involve regulation of serum vitamin D3 and alleviation of the impairments in liver and kidney function.}, } @article {pmid38431829, year = {2024}, author = {Yuan, W and Lin, J and Wang, J and Wang, C and Shan, Y and Jing, W and Fei, Z and Pan, W}, title = {Network pharmacology analysis and clinical efficacy of the traditional Chinese medicine Bu-Shen-Jian-Pi. Part 2: Modulation of hypoxia, redox status, and mitochondrial protection in a neuroblastoma cell line, SH-SY5Y.}, journal = {International journal of clinical pharmacology and therapeutics}, volume = {62}, number = {4}, pages = {162-168}, doi = {10.5414/CP204505}, pmid = {38431829}, issn = {0946-1965}, mesh = {Humans ; *Medicine, Chinese Traditional ; Kaempferols/pharmacology ; Cell Line, Tumor ; Network Pharmacology ; *Neuroblastoma/drug therapy/metabolism ; Oxidation-Reduction ; Hypoxia/drug therapy ; Treatment Outcome ; }, abstract = {OBJECTIVE: To examine the mitochondrial protective effects of icariin, naringenin, kaempferol, and formononetin, potentially active agents in Bu-Shen-Jian-Pi formula (BSJP) identified using network pharmacology analysis.

MATERIALS AND METHODS: Mitochondrial protection activity was determined using a hypoxia-reoxygenation in vitro model based on the neuroblastoma cell line SH-SY5Y and measurements of anti-ferroptotic activity.

RESULTS: Icariin, naringenin, kaempferol, and formononetin showed mitochondrial protective activity involving diverse signaling pathways. The cytoprotective effects of formononetin depended on the inhibition of ferroptosis. Hypoxia-reoxygenation stimulation induced ferroptosis in SH-SY5Y cells.

DISCUSSION: Ferroptosis is a key mechanism in nervous system diseases and is associated with hypoxia-reoxygenation injury. Naringenin and kaempferol were devoid of anti-ferroptotic activity.

CONCLUSION: Evidence has been obtained showing that the core components: icariin, naringenin, kaempferol, and formononetin in BSJP formula have anti-hypoxic and mitochondrial protective activity of potential clinical importance in the treatment of amyotrophic lateral sclerosis and patients with symptoms of hypoxia.}, } @article {pmid38431694, year = {2024}, author = {Mouhamed, AA and Nadim, AH and Mostafa, NM and Eltanany, BM}, title = {Application of smart chemometric models for spectra resolution and determination of challenging multi-action quaternary mixture: statistical comparison with greenness assessment.}, journal = {BMC chemistry}, volume = {18}, number = {1}, pages = {44}, pmid = {38431694}, issn = {2661-801X}, abstract = {A multivariate spectrophotometric method is a potential approach that enables discrimination of spectra of components in complex matrices (e.g., pharmaceutical formulation) serving as a substitution method for chromatography. Four green smart multivariate spectrophotometric models were proposed and validated, including principal component regression (PCR), partial least-squares (PLS), multivariate curve resolution-alternating least squares (MCR-ALS), and artificial neural networks (ANN). The developed chemometric models were compared to resolve highly overlapping spectra of Paracetamol (PARA), Chlorpheniramine maleate (CPM), Caffeine (CAF), and Ascorbic acid (ASC). The four multivariate calibration models were assessed via recoveries percent, and root mean square error of prediction. Hence, the proposed models were efficiently applied with no need for any preliminary separation step. The models were utilized to analyze the studied components in their combined pharmaceutical formulation (Grippostad® C capsules). Analytical GREEnness Metric Approach (AGREE) and eco-scale tools were applied to assess the greenness of the established models and found to be 0.77 and 85, respectively. Moreover, the proposed models have been compared to official ones showing no considerable variations in accuracy and precision. Therefore, these models can be highly advantageous for conducting standard pharmaceutical analysis of the substances researched within product testing laboratories.}, } @article {pmid38430933, year = {2024}, author = {Li, D and Zhou, L and Cao, Z and Wang, J and Yang, H and Lyu, M and Zhang, Y and Yang, R and Wang, J and Bian, Y and Xu, W and Wang, Y}, title = {Associations of environmental factors with neurodegeneration: An exposome-wide Mendelian randomization investigation.}, journal = {Ageing research reviews}, volume = {95}, number = {}, pages = {102254}, doi = {10.1016/j.arr.2024.102254}, pmid = {38430933}, issn = {1872-9649}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics ; *Exposome ; Genome-Wide Association Study ; Mendelian Randomization Analysis ; *Alzheimer Disease/genetics ; *Parkinson Disease ; *Multiple Sclerosis/genetics ; }, abstract = {Neurodegenerative diseases (NDDs) remain a global health challenge. Previous studies have reported potential links between environmental factors and NDDs, however, findings remain controversial across studies and elusive to be interpreted as evidence of robust causal associations. In this study, we comprehensively explored the causal associations of the common environmental factors with major NDDs including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS), based on updated large-scale genome-wide association study data through two-sample Mendelian randomization (MR) approach. Our results indicated that, overall, 28 significant sets of exposure-outcome causal association evidence were detected, 12 of which were previously underestimated and newly identified, including average weekly beer plus cider intake, strenuous sports or other exercises, diastolic blood pressure, and body fat percentage with AD, alcohol intake frequency with PD, apolipoprotein B, systolic blood pressure, and forced expiratory volume in 1 s (FEV1) with ALS, and alcohol intake frequency, hip circumference, forced vital capacity, and FEV1 with MS. Moreover, the causal effects of several environmental factors on NDDs were found to overlap. From a triangulation perspective, our investigation provided insights into understanding the associations of environmental factors with NDDs, providing causality-oriented evidence to establish the risk profile of NDDs.}, } @article {pmid38430277, year = {2024}, author = {Jagaraj, CJ and Shadfar, S and Kashani, SA and Saravanabavan, S and Farzana, F and Atkin, JD}, title = {Molecular hallmarks of ageing in amyotrophic lateral sclerosis.}, journal = {Cellular and molecular life sciences : CMLS}, volume = {81}, number = {1}, pages = {111}, pmid = {38430277}, issn = {1420-9071}, support = {1095215//National Institute for Dementia Research/ ; Peter Stearne Familial MND Research Grant//Motor Neurone Disease Australia/ ; Linda Rynalski Bridge Funding Grant//Motor Neurone Disease Australia/ ; 51909/00//FightMND/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics ; Longevity ; Autophagy/genetics ; Brain ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal, severely debilitating and rapidly progressing disorder affecting motor neurons in the brain, brainstem, and spinal cord. Unfortunately, there are few effective treatments, thus there remains a critical need to find novel interventions that can mitigate against its effects. Whilst the aetiology of ALS remains unclear, ageing is the major risk factor. Ageing is a slowly progressive process marked by functional decline of an organism over its lifespan. However, it remains unclear how ageing promotes the risk of ALS. At the molecular and cellular level there are specific hallmarks characteristic of normal ageing. These hallmarks are highly inter-related and overlap significantly with each other. Moreover, whilst ageing is a normal process, there are striking similarities at the molecular level between these factors and neurodegeneration in ALS. Nine ageing hallmarks were originally proposed: genomic instability, loss of telomeres, senescence, epigenetic modifications, dysregulated nutrient sensing, loss of proteostasis, mitochondrial dysfunction, stem cell exhaustion, and altered inter-cellular communication. However, these were recently (2023) expanded to include dysregulation of autophagy, inflammation and dysbiosis. Hence, given the latest updates to these hallmarks, and their close association to disease processes in ALS, a new examination of their relationship to pathophysiology is warranted. In this review, we describe possible mechanisms by which normal ageing impacts on neurodegenerative mechanisms implicated in ALS, and new therapeutic interventions that may arise from this.}, } @article {pmid38430248, year = {2024}, author = {Ullah, I and Uddin, S and Zhao, L and Wang, X and Li, H}, title = {Autophagy and UPS pathway contribute to nicotine-induced protection effect in Parkinson's disease.}, journal = {Experimental brain research}, volume = {242}, number = {4}, pages = {971-986}, pmid = {38430248}, issn = {1432-1106}, support = {81403145//National Natural Science Foundation of China/ ; 20JR10RA602//Natural Science Foundation of Gansu Province/ ; lzujbky- 2017-206//Fundamental Research Funds for the Central Universities/ ; lzujbky-2018-136//Fundamental Research Funds for the Central Universities/ ; 2019HZ-02//Science and Technology Program of Gansu Province/ ; 2010-1-154//Science and Technology Program of Gansu Province/ ; }, mesh = {Animals ; Humans ; Aged ; *Parkinson Disease/drug therapy/metabolism ; Nicotine/pharmacology/metabolism ; Caenorhabditis elegans/metabolism ; Lipofuscin/metabolism/pharmacology ; alpha-Synuclein/metabolism/pharmacology ; *Neurodegenerative Diseases/metabolism ; Dopaminergic Neurons/metabolism ; Autophagy ; }, abstract = {The gradual nature of age-related neurodegeneration causes Parkinson's disease (PD) and impairs movement, memory, intellectual ability, and social interaction. One of the most prevalent neurodegenerative conditions affecting the central nervous system (CNS) among the elderly is PD. PD affects both motor and cognitive functions. Degeneration of dopaminergic (DA) neurons and buildup of the protein α-synuclein (α-Syn) in the substantia nigra pars compacta (SNpc) are two major causes of this disorder. Both UPS and ALS systems serve to eliminate α-Syn. Autophagy and UPS deficits, shortened life duration, and lipofuscin buildup accelerate PD. This sickness has no cure. Innovative therapies are halting PD progression. Bioactive phytochemicals may provide older individuals with a natural substitute to help delay the onset of neurodegenerative illnesses. This study examines whether nicotine helps transgenic C. elegans PD models. According to numerous studies, nicotine enhances synaptic plasticity and dopaminergic neuronal survival. Upgrades UPS pathways, increases autophagy, and decreases oxidative stress and mitochondrial dysfunction. At 100, 150, and 200 µM nicotine levels, worms showed reduced α-Syn aggregation, repaired DA neurotoxicity after 6-OHDA intoxication, increased lifetime, and reduced lipofuscin accumulation. Furthermore, nicotine triggered autophagy and UPS. We revealed nicotine's potential as a UPS and autophagy activator to prevent PD and other neurodegenerative diseases.}, } @article {pmid38429929, year = {2024}, author = {Schuster, KH and Zalon, AJ and DiFranco, DM and Putka, AF and Stec, NR and Jarrah, SI and Naeem, A and Haque, Z and Zhang, H and Guan, Y and McLoughlin, HS}, title = {ASOs are an effective treatment for disease-associated oligodendrocyte signatures in premanifest and symptomatic SCA3 mice.}, journal = {Molecular therapy : the journal of the American Society of Gene Therapy}, volume = {32}, number = {5}, pages = {1359-1372}, pmid = {38429929}, issn = {1525-0024}, support = {R01 NS122751/NS/NINDS NIH HHS/United States ; R35 GM133346/GM/NIGMS NIH HHS/United States ; U01 NS106670/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; *Oligodendroglia/metabolism ; Mice ; *Machado-Joseph Disease/genetics/therapy/pathology/metabolism ; *Oligonucleotides, Antisense ; *Disease Models, Animal ; *Ataxin-3/genetics/metabolism ; Humans ; Repressor Proteins/genetics/metabolism ; Mice, Transgenic ; }, abstract = {Spinocerebellar ataxia type 3 (SCA3) is the most common dominantly inherited ataxia. Currently, no preventive or disease-modifying treatments exist for this progressive neurodegenerative disorder, although efforts using gene silencing approaches are under clinical trial investigation. The disease is caused by a CAG repeat expansion in the mutant gene, ATXN3, producing an enlarged polyglutamine tract in the mutant protein. Similar to other paradigmatic neurodegenerative diseases, studies evaluating the pathogenic mechanism focus primarily on neuronal implications. Consequently, therapeutic interventions often overlook non-neuronal contributions to disease. Our lab recently reported that oligodendrocytes display some of the earliest and most progressive dysfunction in SCA3 mice. Evidence of disease-associated oligodendrocyte signatures has also been reported in other neurodegenerative diseases, including Alzheimer's disease, amyotrophic lateral sclerosis, Parkinson's disease, and Huntington's disease. Here, we assess the effects of anti-ATXN3 antisense oligonucleotide (ASO) treatment on oligodendrocyte dysfunction in premanifest and symptomatic SCA3 mice. We report a severe, but modifiable, deficit in oligodendrocyte maturation caused by the toxic gain-of-function of mutant ATXN3 early in SCA3 disease that is transcriptionally, biochemically, and functionally rescued with anti-ATXN3 ASO. Our results highlight the promising use of an ASO therapy across neurodegenerative diseases that requires glial targeting in addition to affected neuronal populations.}, } @article {pmid38429818, year = {2024}, author = {Darabi, S and Ariaei, A and Rustamzadeh, A and Afshari, D and Charkhat Gorgich, EA and Darabi, L}, title = {Cerebrospinal fluid and blood exosomes as biomarkers for amyotrophic lateral sclerosis; a systematic review.}, journal = {Diagnostic pathology}, volume = {19}, number = {1}, pages = {47}, pmid = {38429818}, issn = {1746-1596}, mesh = {Humans ; *Exosomes ; *Amyotrophic Lateral Sclerosis/diagnosis ; Superoxide Dismutase-1 ; Biomarkers ; DNA-Binding Proteins ; Disease Progression ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive and fatal motor neuron disease. Due to the limited knowledge about potential biomarkers that help in early diagnosis and monitoring disease progression, today's diagnoses are based on ruling out other diseases, neurography, and electromyography examination, which takes a time-consuming procedure.

METHODS: PubMed, ScienceDirect, and Web of Science were explored to extract articles published from January 2015 to June 2023. In the searching strategy following keywords were included; amyotrophic lateral sclerosis, biomarkers, cerebrospinal fluid, serum, and plama.

RESULTS: A total number of 6 studies describing fluid-based exosomal biomarkers were included in this study. Aggregated proteins including SOD1, TDP-43, pTDP-43, and FUS could be detected in the microvesicles (MVs). Moreover, TDP-43 and NFL extracted from plasma exosomes could be used as prognostic biomarkers. Also, downregulated miR-27a-3p detected through exoEasy Maxi and exoQuick Kit in the plasma could be measured as a diagnostic biomarker. Eventually, the upregulated level of CORO1A could be used to monitor disease progression.

CONCLUSION: Based on the results, each biomarker alone is insufficient to evaluate ALS. CNS-derived exosomes contain multiple ALS-related biomarkers (SOD1, TDP-43, pTDP-43, FUS, and miRNAs) that are detectable in cerebrospinal fluid and blood is a proper alternation. Exosome detecting kits listed as exoEasy, ExoQuick, Exo-spin, ME kit, ExoQuick Plus, and Exo-Flow, are helpful to reach this purpose.}, } @article {pmid38429713, year = {2024}, author = {Hagenaar, DA and Bindels-de Heus, KGCB and van Gils, MM and van den Berg, L and Ten Hoopen, LW and Affourtit, P and Pel, JJM and Joosten, KFM and Hillegers, MHJ and Moll, HA and de Wit, MY and Dieleman, GC and Mous, SE}, title = {Outcome measures in Angelman syndrome.}, journal = {Journal of neurodevelopmental disorders}, volume = {16}, number = {1}, pages = {6}, pmid = {38429713}, issn = {1866-1955}, support = {B17-04A//Stichting Vrienden van het Sophia/ ; }, mesh = {Child ; Humans ; *Angelman Syndrome/complications/diagnosis ; Reproducibility of Results ; Body Composition ; Plethysmography/methods ; Electric Impedance ; }, abstract = {BACKGROUND: Angelman syndrome (AS) is a rare neurodevelopmental disorder characterized by severe intellectual disability, little to no expressive speech, visual and motor problems, emotional/behavioral challenges, and a tendency towards hyperphagia and weight gain. The characteristics of AS make it difficult to measure these children's functioning with standard clinical tests. Feasible outcome measures are needed to measure current functioning and change over time, in clinical practice and clinical trials.

AIM: Our first aim is to assess the feasibility of several functional tests. We target domains of neurocognitive functioning and physical growth using the following measurement methods: eye-tracking, functional Near-Infrared Spectroscopy (fNIRS), indirect calorimetry, bio-impedance analysis (BIA), and BOD POD (air-displacement plethysmography). Our second aim is to explore the results of the above measures, in order to better understand the AS phenotype.

METHODS: The study sample consisted of 28 children with AS aged 2-18 years. We defined an outcome measure as feasible when (1) at least 70% of participants successfully finished the measurement and (2) at least 60% of those participants had acceptable data quality. Adaptations to the test procedure and reasons for early termination were noted. Parents rated acceptability and importance and were invited to make recommendations to increase feasibility. The results of the measures were explored.

RESULTS: Outcome measures obtained with eye-tracking and BOD POD met the definition of feasibility, while fNIRS, indirect calorimetry, and BIA did not. The most important reasons for early termination of measurements were showing signs of protest, inability to sit still and poor/no calibration (eye-tracking specific). Post-calibration was often applied to obtain valid eye-tracking results. Parents rated the BOD POD als most acceptable and fNIRS as least acceptable for their child. All outcome measures were rated to be important. Exploratory results indicated longer reaction times to high salient visual stimuli (eye-tracking) as well as high body fat percentage (BOD POD).

CONCLUSIONS: Eye-tracking and BOD POD are feasible measurement methods for children with AS. Eye-tracking was successfully used to assess visual orienting functions in the current study and (with some practical adaptations) can potentially be used to assess other outcomes as well. BOD POD was successfully used to examine body composition.

TRIAL REGISTRATION: Registered d.d. 23-04-2020 under number 'NL8550' in the Dutch Trial Register: https://onderzoekmetmensen.nl/en/trial/23075.}, } @article {pmid38429379, year = {2024}, author = {de Luzy, IR and Lee, MK and Mobley, WC and Studer, L}, title = {Lessons from inducible pluripotent stem cell models on neuronal senescence in aging and neurodegeneration.}, journal = {Nature aging}, volume = {4}, number = {3}, pages = {309-318}, pmid = {38429379}, issn = {2662-8465}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; R01 AG054720/AG/NIA NIH HHS/United States ; R01 AG070154/AG/NIA NIH HHS/United States ; ASAP-020370//Michael J. Fox Foundation for Parkinson's Research (Michael J. Fox Foundation)/ ; }, mesh = {Humans ; *Neurodegenerative Diseases ; Aging ; Cellular Senescence/physiology ; Neurons ; *Pluripotent Stem Cells ; }, abstract = {Age remains the central risk factor for many neurodegenerative diseases including Parkinson's disease, Alzheimer's disease and amyotrophic lateral sclerosis. Although the mechanisms of aging are complex, the age-related accumulation of senescent cells in neurodegeneration is well documented and their clearance can alleviate disease-related features in preclinical models. Senescence-like characteristics are observed in both neuronal and glial lineages, but their relative contribution to aging and neurodegeneration remains unclear. Human pluripotent stem cell-derived neurons provide an experimental model system to induce neuronal senescence. However, the extensive heterogeneity in the profile of senescent neurons and the methods to assess senescence remain major challenges. Here, we review the evidence of cellular senescence in neuronal aging and disease, discuss human pluripotent stem cell-based model systems used to investigate neuronal senescence and propose a panel of cellular and molecular hallmarks to characterize senescent neurons. Understanding the role of neuronal senescence may yield novel therapeutic opportunities in neurodegenerative disease.}, } @article {pmid38429156, year = {2024}, author = {Corcia, P and Couratier, P}, title = {Spreading of motor neuron degeneration in ALS is not so random.}, journal = {Revue neurologique}, volume = {180}, number = {6}, pages = {475-476}, doi = {10.1016/j.neurol.2024.02.384}, pmid = {38429156}, issn = {0035-3787}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/pathology/diagnosis ; *Motor Neurons/pathology/physiology ; *Nerve Degeneration/pathology ; }, } @article {pmid38428880, year = {2024}, author = {Hu, CJ and Chen, PC and Padmanabhan, N and Zahn, A and Ho, CM and Wang, K and Yen, Y}, title = {A new potential therapeutic approach for ALS: A case report with NGS analysis.}, journal = {Medicine}, volume = {103}, number = {9}, pages = {e37401}, pmid = {38428880}, issn = {1536-5964}, mesh = {Humans ; Male ; Aged ; Riluzole/therapeutic use ; *Amyotrophic Lateral Sclerosis/diagnosis/drug therapy/genetics ; Artificial Intelligence ; Treatment Outcome ; *Hypotension/drug therapy ; }, abstract = {RATIONALE: Amyotrophic lateral sclerosis (ALS) poses a significant clinical challenge due to its rapid progression and limited treatment options, often leading to deadly outcomes. Looking for effective therapeutic interventions is critical to improve patient outcomes in ALS.

PATIENT CONCERNS: The patient, a 75-year-old East Asian male, manifested an insidious onset of right-hand weakness advancing with dysarthria. Comprehensive Next-generation sequencing analysis identified variants in specific genes consistent with ALS diagnosis.

DIAGNOSES: ALS diagnosis is based on El Escorial diagnostic criteria.

INTERVENTIONS: This study introduces a novel therapeutic approach using artificial intelligence phenotypic response surface (AI-PRS) technology to customize personalized drug-dose combinations for ALS. The patient underwent a series of phases of AI-PRS-assisted trials, initially incorporating a 4-drug combination of Ibudilast, Riluzole, Tamoxifen, and Ropinirole. Biomarkers and regular clinical assessments, including nerve conduction velocity, F-wave, H-reflex, electromyography, and motor unit action potential, were monitored to comprehensively evaluate treatment efficacy.

OUTCOMES: Neurophysiological assessments supported the ALS diagnosis and revealed the co-presence of diabetic polyneuropathy. Hypotension during the trial necessitated an adaptation to a 2-drug combinational trial (ibudilast and riluzole). Disease progression assessment shifted exclusively to clinical tests of muscle strength, aligning with the patient's well-being.

LESSONS: The study raises the significance of personalized therapeutic strategies in ALS by AI-PRS. It also emphasizes the adaptability of interventions based on patient-specific responses. The encountered hypotension incident highlights the importance of attentive monitoring and personalized adjustments in treatment plans. The described therapy using AI-PRS, offering personalized drug-dose combinations technology is a potential approach in treating ALS. The promising outcomes warrant further evaluation in clinical trials for searching a personalized, more effective combinational treatment for ALS patients.}, } @article {pmid38428228, year = {2024}, author = {Masroor, A and Zaidi, N and Nabi, F and Malik, S and Zehra, S and Arjmand, F and Naseem, N and Khan, RH}, title = {Biophysical insight into anti-amyloidogenic nature of novel ionic Co(II)(phen)(H2O)4][+][glycinate][-] chemotherapeutic drug candidate against human lysozyme aggregation.}, journal = {Biophysical chemistry}, volume = {308}, number = {}, pages = {107214}, doi = {10.1016/j.bpc.2024.107214}, pmid = {38428228}, issn = {1873-4200}, mesh = {Humans ; *Amyloid/chemistry ; Muramidase/chemistry ; Molecular Docking Simulation ; *Amyloidosis/drug therapy/metabolism ; Dynamic Light Scattering ; Protein Aggregates ; }, abstract = {In the recent past, there has been an ever-increasing interest in the search for metal-based therapeutic drug candidates for protein misfolding disorders (PMDs) particularly neurodegenerative disorders such as Alzheimer's, Parkinson's, Prion's diseases, and amyotrophic lateral sclerosis. Also, different amyloidogenic variants of human lysozyme (HL) are involved in hereditary systemic amyloidosis. Metallo-therapeutic agents are extensively studied as antitumor agents, however, they are relatively unexplored for the treatment of non-neuropathic amyloidoses. In this work, inhibition potential of a novel ionic cobalt(II) therapeutic agent (CoTA) of the formulation [Co(phen)(H2O)4][+][glycinate][-] is evaluated against HL fibrillation. Various biophysical techniques viz., dye-binding assays, dynamic light scattering (DLS), differential scanning calorimetry (DSC), electron microscopy, and molecular docking experiments validate the proposed mechanism of inhibition of HL fibrillation by CoTA. The experimental corroborative results of these studies reveal that CoTA can suppress and slow down HL fibrillation at physiological temperature and pH. DLS and 1-anilino-8-naphthalenesulfonate (ANS) assay show that reduced fibrillation in the presence of CoTA is marked by a significant decrease in the size and hydrophobicity of the aggregates. Fluorescence quenching and molecular docking results demonstrate that CoTA binds moderately to the aggregation-prone region of HL (Kb = 6.6 × 10[4] M[-1]), thereby, inhibiting HL fibrillation. In addition, far-UV CD and DSC show that binding of CoTA to HL does not cause any change in the stability of HL. More importantly, CoTA attenuates membrane damaging effects of HL aggregates against RBCs. This study identifies inorganic metal complexes as a therapeutic intervention for systemic amyloidosis.}, } @article {pmid38428126, year = {2024}, author = {Wahbeh, F and Restifo, D and Laws, S and Pawar, A and Parikh, NS}, title = {Impact of tobacco smoking on disease-specific outcomes in common neurological disorders: A scoping review.}, journal = {Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia}, volume = {122}, number = {}, pages = {10-18}, pmid = {38428126}, issn = {1532-2653}, support = {K23 AG073524/AG/NIA NIH HHS/United States ; }, mesh = {Humans ; *Smoking Cessation ; Smoking/adverse effects/epidemiology ; Tobacco Smoking ; *Stroke/epidemiology/etiology/therapy ; *Multiple Sclerosis ; }, abstract = {Although the association of smoking with the risk of incident neurological disorders is well established, less is known about the impact of smoking and smoking cessation on outcomes of these conditions. The objective of this scoping review was to synthesize what is known about the impact of smoking and smoking cessation on disease-specific outcomes for seven common neurological disorders. We included 67 studies on the association of smoking and smoking cessation on disease-specific outcomes. For multiple sclerosis, smoking was associated with greater clinical and radiological disease progression, relapses, risk for disease-related death, cognitive decline, and mood symptoms, in addition to reduced treatment effectiveness. For stroke and transient ischemic attack, smoking was associated with greater rates of stroke recurrence, post-stroke cardiovascular outcomes, post-stroke mortality, post-stroke cognitive impairment, and functional impairment. In patients with cognitive impairment and dementia, smoking was associated with faster cognitive decline, and smoking was also associated with greater cognitive decline in Parkinson's disease, but not motor symptom worsening. Patients with amyotrophic lateral sclerosis who smoked faced increased mortality. Last, in patients with cluster headache, smoking was associated with more frequent and longer cluster attack periods. Conversely, for multiple sclerosis and stroke, smoking cessation was associated with improved disease-specific outcomes. In summary, whereas smoking is detrimentally associated with disease-specific outcomes in common neurological conditions, there is growing evidence that smoking cessation may improve outcomes. Effective smoking cessation interventions should be leveraged in the management of common neurological disorders to improve patient outcomes.}, } @article {pmid38427990, year = {2024}, author = {El-Hajj, VG and Daller, C and Fletcher-Sandersjöö, A and Gharios, M and Bydon, M and Söderman, M and Jabbour, P and Edström, E and Elmi-Terander, A and Arnberg, F}, title = {The negative impact of treatment delays on the long-term neurological outcomes of spinal dural arteriovenous fistulas: a longitudinal cohort study.}, journal = {Neurosurgical focus}, volume = {56}, number = {3}, pages = {E14}, doi = {10.3171/2023.12.FOCUS23703}, pmid = {38427990}, issn = {1092-0684}, mesh = {Humans ; Male ; Aged ; Female ; Cohort Studies ; Longitudinal Studies ; Retrospective Studies ; *Treatment Delay ; *Central Nervous System Vascular Malformations/complications/surgery ; }, abstract = {OBJECTIVE: Dural arteriovenous fistulas are rare vascular malformations that affect the brain and spinal cord. Spinal dural arteriovenous fistulas (sdAVFs) are the most frequently encountered vascular malformation affecting the spinal cord. The object of this study was to evaluate the impact of treatment delays on the long-term neurological outcomes of either open surgical or interventional treatment of sdAVFs.

METHODS: In this retrospective, population-based cohort study, the authors examined consecutive patients with diagnosed sdAVFs at a tertiary care center between 2005 and 2020. Patients were assessed using the Aminoff-Logue disability scale (ALS) at various time points including symptom onset, primary care visit, first specialist outpatient visit, as well as both short and long-term follow-ups. The postoperative long-term ALS gait and bladder grades constituted the primary outcomes of the study.

RESULTS: Among the 34 patients included in the study, the median age was 65 years, and there was a male predominance (71%). Most lesions were in the lumbar region (47%). Significant worsening in ALS gait and bladder grades was observed preoperatively, followed by postoperative improvements (p < 0.05). There was no difference in outcomes between surgical and endovascular treatments. Older age (OR 1.10, 95% CI 1.03-1.17, p = 0.007), worse preoperative ALS gait grades (OR 5.12, 95% CI 2.18-12.4, p < 0.001), and longer time from first specialist outpatient visit to first treatment (OR 1.00, 95% CI 1.00-1.01, p = 0.040) were independently associated with worse long-term gait outcomes. Only the preoperative ALS bladder score was a predictor of worse long-term bladder function (OR 92.7, 95% CI 28.0-306.7, p < 0.001).

CONCLUSIONS: Both surgical and endovascular treatments for sdAVFs led to significant neurological improvements. However, treatment delays were associated with less favorable long-term outcomes. Prompt diagnosis and early intervention prior to symptom progression may enhance recovery and help to preserve neurological function.}, } @article {pmid38427252, year = {2024}, author = {Rajaratnam, S and Pradhan, SS and Naik, AA and Sivaramakrishnan, V}, title = {Integrated Multi-Omics Analysis and Validation in Yeast Model of Amyotrophic Lateral Sclerosis.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {2761}, number = {}, pages = {397-419}, pmid = {38427252}, issn = {1940-6029}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/metabolism ; Saccharomyces cerevisiae/genetics ; Multiomics ; Software ; Gene Expression Profiling ; }, abstract = {Transcriptomics is a complex process that involves raw data extraction, normalization, differential gene expression, and analysis. The Gene Expression Omnibus (GEO) database at the National Center for Biotechnology Information (NCBI) is a repository of experimental datasets. Amyotrophic lateral sclerosis (ALS) datasets are deposited by various scientists and research investigators to expand the horizon of scientific knowledge. R-statistical tools are the most common ways for conducting these kinds of studies. The first step is the identification of appropriate datasets. Since the raw data is available in a variety of formats, a large array of software is used for extraction and analysis. Normalization is conducted for the datasets using NetworkAnalyst. Differential analysis is further conducted on the normalized data to identify significantly enriched genes. The significant genes are then grouped into pathways. The results were validated using yeast model of ALS in which the yeast is transformed with ALS plasmids encoding genes associated with ALS. The resulting GFP-tagged protein aggregates are imaged using fluorescence microscopy and subsequently validated using filter retardation assay and quantified using ImageJ software. Functional role of different genes is studied using metabolite treatment and knockout studies.}, } @article {pmid38427251, year = {2024}, author = {Niccolai, E and Martinelli, I and Quaranta, G and Nannini, G and Zucchi, E and De Maio, F and Gianferrari, G and Bibbò, S and Cammarota, G and Mandrioli, J and Masucci, L and Amedei, A}, title = {Fecal Microbiota Transplantation in Amyotrophic Lateral Sclerosis: Clinical Protocol and Evaluation of Microbiota Immunity Axis.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {2761}, number = {}, pages = {373-396}, pmid = {38427251}, issn = {1940-6029}, mesh = {Humans ; Fecal Microbiota Transplantation ; *Amyotrophic Lateral Sclerosis/therapy ; *Microbiota ; *Gastrointestinal Microbiome/physiology ; Clinical Protocols ; Multicenter Studies as Topic ; Randomized Controlled Trials as Topic ; }, abstract = {The fecal microbial transplantation (FMT) is a therapeutic transplant of fecal microbiota from healthy donors to patients. This practice is aimed at restoring eubiosis and rebalancing the enteric and systemic immune responses, and then eliminating pathogenic triggers of multiple disease, including neurodegenerative diseases. Alterations of gut microbiota (GM) affect the central nervous system (CNS) health, impacting neuro-immune interactions, synaptic plasticity, myelination, and skeletal muscle function. T-regulatory lymphocytes (Treg) are among the most important players in the pathogenesis of amyotrophic lateral sclerosis (ALS), altering the disease course. Along with circulating neuropeptides, other immune cells, and the gut-brain axis, the GM influences immunological tolerance and controls Treg's number and suppressive functions. A double-blind, controlled, multicenter study on FMT in ALS patients has been designed to evaluate if FMT can modulate neuroinflammation, by restoring Treg number, thus modifying disease activity and progression.}, } @article {pmid38427163, year = {2024}, author = {Cioffi, E and Gioiosa, V and Tessa, A and Petrucci, A and Trovato, R and Santorelli, FM and Casali, C}, title = {Hereditary spastic paraparesis type 18 (SPG18): new ERLIN2 variants in a series of Italian patients, shedding light upon genetic and phenotypic variability.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {45}, number = {8}, pages = {3845-3852}, pmid = {38427163}, issn = {1590-3478}, mesh = {Humans ; Italy ; Male ; Female ; *Phenotype ; Adult ; *Membrane Proteins/genetics ; Middle Aged ; Mutation ; Spastic Paraplegia, Hereditary/genetics ; }, abstract = {INTRODUCTION: Hereditary spastic paraparesis (HSP) is a group of central nervous system diseases primarily affecting the spinal upper motor neurons, with different inheritance patterns and phenotypes. SPG18 is a rare, early-onset, complicated HSP, first reported as linked to biallelic ERLIN2 mutations. Recent cases of late-onset, pure HSP with monoallelic ERLIN2 variants prompt inquiries into the zygosity of such genetic conditions. The observed relationship between phenotype and mode of inheritance suggests a potential dominant negative effect of mutated ERLIN2 protein, potentially resulting in a milder phenotype. This speculation suggests that a wider range of HSP genes could be linked to various inheritance patterns.

PURPOSE AND BACKGROUND: With documented cases of HSP loci exhibiting both dominant and recessive patterns, this study emphasizes that the concept of zygosity is no longer a limiting factor in the establishment of molecular diagnoses for HSP. Recent cases have demonstrated phenoconversion in SPG18, from HSP to an amyotrophic lateral sclerosis (ALS)-like syndrome.

METHODS AND RESULTS: This report highlights two cases out of five exhibiting HSP-ALS phenoconversion, discussing an observed prevalence in autosomal dominant SPG18. Additionally, the study emphasizes the relatively high incidence of the c.502G>A variant in monoallelic SPG18 cases. This mutation appears to be particularly common in cases of HSPALS phenoconversion, indicating its potential role as a hotspot for a distinctive SPG18 phenotype with an ALS-like syndrome.

CONCLUSIONS: Clinicians need to be aware that patients with HSP may show ALS signs and symptoms. On the other hand, HSP panels must be included in genetic testing methods for instances of familial ALS.}, } @article {pmid38426720, year = {2024}, author = {Pei, Y and Liu, S and Wang, L and Chen, C and Hu, M and Xue, Y and Guan, D and Xie, L and Liao, H and Zhou, J and Zhang, H}, title = {Design, Synthesis, and Biological Evaluation of Eukaryotic Initiation Factor 2B (eIF2B) Activators.}, journal = {ChemMedChem}, volume = {19}, number = {11}, pages = {e202300716}, doi = {10.1002/cmdc.202300716}, pmid = {38426720}, issn = {1860-7187}, support = {LG202103-02-08//Lingang Laboratory/ ; }, mesh = {Humans ; *Activating Transcription Factor 4/metabolism ; *Drug Design ; HeLa Cells ; Structure-Activity Relationship ; *Eukaryotic Initiation Factor-2B/metabolism/antagonists & inhibitors ; Molecular Structure ; Dose-Response Relationship, Drug ; Oxadiazoles/pharmacology/chemistry/chemical synthesis ; }, abstract = {The eukaryotic initiation factor 2B (eIF2B) is a key regulator in protein-regulated signaling pathways and is closely related to the function of the central nervous system. Modulating eIF2B could retard the process of neurodegenerative diseases, including Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), and vanishing white matter disease (VWM) et al. Here, we designed and synthesized a series of novel eIF2B activators containing oxadiazole fragments. The activating effects of compounds on eIF2B were investigated through testing the inhibition of ATF4 expression. Of all the targeted compounds, compounds 21 and 29 exhibited potent inhibition on ATF4 expression with IC50 values of 32.43 nM and 47.71 nM, respectively, which were stronger than that of ISRIB (IC50=67.90 nM). ATF4 mRNA assay showed that these two compounds could restore ATF4 mRNA to normal levels in thapsigargin-stimulated HeLa cells. Protein Translation assay showed that both compounds were effective in restoring protein synthesis. Compound potency assay showed that both compounds had similar potency to ISRIB with EC50 values of 5.844 and 37.70 nM. Cytotoxicity assay revealed that compounds 21 and 29 had low toxicity and were worth further investigation.}, } @article {pmid38426489, year = {2024}, author = {Rotem, RS and Bellavia, A and Paganoni, S and Weisskopf, MG}, title = {Medication use and risk of amyotrophic lateral sclerosis: using machine learning for an exposome-wide screen of a large clinical database.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {25}, number = {3-4}, pages = {367-375}, pmid = {38426489}, issn = {2167-9223}, support = {P30 ES000002/ES/NIEHS NIH HHS/United States ; R21 NS099910/NS/NINDS NIH HHS/United States ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/epidemiology/etiology ; *Exposome ; Bayes Theorem ; Machine Learning ; Vitamin E ; }, abstract = {BACKGROUND: Accumulating evidence suggests that non-genetic factors have important etiologic roles in amyotrophic lateral sclerosis (ALS), yet identification of specific culprit factors has been challenging. Many medications target biological pathways implicated in ALS pathogenesis, and screening large pharmacologic datasets for signals could greatly accelerate the identification of risk-modulating pharmacologic factors for ALS.

METHOD: We conducted a high-dimensional screening of patients' history of medication use and ALS risk using an advanced machine learning approach based on gradient-boosted decision trees coupled with Bayesian model optimization and repeated data sampling. Clinical and medication dispensing data were obtained from a large Israeli health fund for 501 ALS cases and 4,998 matched controls using a lag period of 3 or 5 years prior to ALS diagnosis for ascertaining medication exposure.

RESULTS: Of over 1,000 different medication classes, we identified 8 classes that were consistently associated with increased ALS risk across independently trained models, where most are indicated for control of symptoms implicated in ALS. Some suggestive protective effects were also observed, notably for vitamin E.

DISCUSSION: Our results indicate that use of certain medications well before the typically recognized prodromal period was associated with ALS risk. This could result because these medications increase ALS risk or could indicate that ALS symptoms can manifest well before suggested prodromal periods. The results also provide further evidence that vitamin E may be a protective factor for ALS. Targeted studies should be performed to elucidate the possible pathophysiological mechanisms while providing insights for therapeutics design.}, } @article {pmid38426231, year = {2024}, author = {Young, CA and Chaouch, A and Mcdermott, CJ and Al-Chalabi, A and Chhetri, SK and Talbot, K and Malaspina, A and Mills, R and Tennant, A}, title = {Improving the measurement properties of the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R): deriving a valid measurement total for the calculation of change.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {25}, number = {3-4}, pages = {400-409}, pmid = {38426231}, issn = {2167-9223}, support = {MALASPINA/APR13/817-791/MNDA_/Motor Neurone Disease Association/United Kingdom ; TURNER/OCT15/972-797/MNDA_/Motor Neurone Disease Association/United Kingdom ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis ; Factor Analysis, Statistical ; Disease Progression ; }, abstract = {BACKGROUND: The Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) total score is a widely used measure of functional status in Amyotrophic Lateral Sclerosis/Motor Neuron Disease (ALS), but recent evidence has raised doubts about its validity. The objective was to examine the measurement properties of the ALSFRS-R, aiming to produce valid measurement from all 12 scale items.

METHOD: Longitudinal ALSFRS-R data were collected between 2013-2020 from 1120 people with ALS recruited from 35 centers, together with other scales in the Trajectories of Outcomes in Neurological Conditions-ALS (TONiC-ALS) study. The ALSFRS-R was analyzed by confirmatory factor analysis (CFA), Rasch Analysis (RA) and Mokken scaling.

RESULTS: No definite factor structure of the ALSFRS-R was confirmed by CFA. RA revealed the raw score total to be invalid even at the ordinal level because of multidimensionality; valid interval level subscale measures could be found for the Bulbar, Fine-Motor and Gross-Motor domains but the Respiratory domain was only valid at an ordinal level. All four domains resolved into a single valid, interval level measure by using a bifactor RA. The smallest detectable difference was 10.4% of the range of the interval scale.

CONCLUSION: A total ALSFRS-R ordinal raw score can lead to inferential bias in clinical trial results due to its non-linear nature. On the interval level transformation, more than 5 points difference is required before a statistically significant detectable difference can be observed. Transformation to interval level data should be mandatory in clinical trials.}, } @article {pmid38424324, year = {2024}, author = {Milioto, C and Carcolé, M and Giblin, A and Coneys, R and Attrebi, O and Ahmed, M and Harris, SS and Lee, BI and Yang, M and Ellingford, RA and Nirujogi, RS and Biggs, D and Salomonsson, S and Zanovello, M and de Oliveira, P and Katona, E and Glaria, I and Mikheenko, A and Geary, B and Udine, E and Vaizoglu, D and Anoar, S and Jotangiya, K and Crowley, G and Smeeth, DM and Adams, ML and Niccoli, T and Rademakers, R and van Blitterswijk, M and Devoy, A and Hong, S and Partridge, L and Coyne, AN and Fratta, P and Alessi, DR and Davies, B and Busche, MA and Greensmith, L and Fisher, EMC and Isaacs, AM}, title = {PolyGR and polyPR knock-in mice reveal a conserved neuroprotective extracellular matrix signature in C9orf72 ALS/FTD neurons.}, journal = {Nature neuroscience}, volume = {27}, number = {4}, pages = {643-655}, pmid = {38424324}, issn = {1546-1726}, support = {MR/V003585/1/MRC_/Medical Research Council/United Kingdom ; G0601056/MRC_/Medical Research Council/United Kingdom ; MR/S006508/1/MRC_/Medical Research Council/United Kingdom ; MC_EX_MR/N501931/1/MRC_/Medical Research Council/United Kingdom ; MR/S017003/1/MRC_/Medical Research Council/United Kingdom ; G0801110/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Animals ; Humans ; Mice ; *Frontotemporal Dementia/pathology ; *Amyotrophic Lateral Sclerosis/metabolism ; Transforming Growth Factor beta1 ; C9orf72 Protein/genetics/metabolism ; *Induced Pluripotent Stem Cells/metabolism ; Motor Neurons/metabolism ; Drosophila ; Extracellular Matrix/metabolism ; Dipeptides/metabolism ; DNA Repeat Expansion/genetics ; }, abstract = {Dipeptide repeat proteins are a major pathogenic feature of C9orf72 amyotrophic lateral sclerosis (C9ALS)/frontotemporal dementia (FTD) pathology, but their physiological impact has yet to be fully determined. Here we generated C9orf72 dipeptide repeat knock-in mouse models characterized by expression of 400 codon-optimized polyGR or polyPR repeats, and heterozygous C9orf72 reduction. (GR)400 and (PR)400 knock-in mice recapitulate key features of C9ALS/FTD, including cortical neuronal hyperexcitability, age-dependent spinal motor neuron loss and progressive motor dysfunction. Quantitative proteomics revealed an increase in extracellular matrix (ECM) proteins in (GR)400 and (PR)400 spinal cord, with the collagen COL6A1 the most increased protein. TGF-β1 was one of the top predicted regulators of this ECM signature and polyGR expression in human induced pluripotent stem cell neurons was sufficient to induce TGF-β1 followed by COL6A1. Knockdown of TGF-β1 or COL6A1 orthologues in polyGR model Drosophila exacerbated neurodegeneration, while expression of TGF-β1 or COL6A1 in induced pluripotent stem cell-derived motor neurons of patients with C9ALS/FTD protected against glutamate-induced cell death. Altogether, our findings reveal a neuroprotective and conserved ECM signature in C9ALS/FTD.}, } @article {pmid38424114, year = {2024}, author = {Bridges, LR}, title = {RNA as a component of scrapie fibrils.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {5011}, pmid = {38424114}, issn = {2045-2322}, support = {P41 GM103311/GM/NIGMS NIH HHS/United States ; R01 GM129325/GM/NIGMS NIH HHS/United States ; }, mesh = {Cricetinae ; Animals ; Sheep ; Humans ; *Scrapie ; RNA ; Cytoskeleton ; *Alzheimer Disease ; Microscopy, Electron ; Cryoelectron Microscopy ; Amyloid/chemistry ; }, abstract = {Recently, electron cryo-microscopy (cryo-EM) maps of fibrils from the brains of mice and hamsters with five infectious scrapie strains have been published and deposited in the electron microscopy data bank (EMDB). As noted by the primary authors, the fibrils contain a second component other than protein. The aim of the present study was to identify the nature of this second component in the published maps using an in silico approach. Extra densities (EDs) containing this component were continuous, straight, axial, at right angles to protein rungs and within hydrogen-bonding distance of protein, consistent with a structural role. EDs co-located with strips of basic residues, notably lysines, and formed a conspicuous cladding over parts of the N-terminal lobe of the protein. A Y-shaped polymer consistent with RNA was found, in places forming a single chain and at one location forming a duplex, comprising two antiparallel chains, and raising the intriguing possibility of replicative behaviour. To reflect the monotonous nature of the protein interface, it is suggested that the RNA may be a short tandem repeat. Fibrils from brains of patients with Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis and other neurodegenerations also contain EDs and may be of a similar aetiology.}, } @article {pmid38421827, year = {2024}, author = {Zhang, Y and Li, Y and Bin, S and Cheng, X and Niu, Q}, title = {A Neglected Gene: The Role of the ANG Gene in the Pathogenesis of Amyotrophic Lateral Sclerosis.}, journal = {Aging and disease}, volume = {16}, number = {1}, pages = {13-32}, pmid = {38421827}, issn = {2152-5250}, abstract = {Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative disease with a poor prognosis. To date, more than 40 ALS-related genes have been identified. However, there is still a lack of targeted therapeutic drugs for the treatment of ALS, especially for patients with acute onset and severe disease. A series of studies reported missense heterozygous mutations with loss of function in the coding region of the ANG gene in ALS patients. ANG deficiency is related to the pathogenesis of ALS, but the underlying mechanism has not been determined. This article aimed to synthesize and consolidate the knowledge of the pathological mechanism of ALS induced by ANG mutation and provide a theoretical basis for ALS diagnosis and targeted therapy. This article further delves into the mechanisms underlying the current understanding of the structure and function of the ANG gene, the association between ANG and ALS, and its pathogenesis. Mutations in ANG may lead to the development of ALS through the loss of neuroprotective function, induction of oxidative stress, or inhibition of rRNA synthesis. ANG mutations and genetic and environmental factors may cause disease heterogeneity and more severe disease than in ALS patients with the wild-type gene. Exploring this mechanism is expected to provide a new approach for ALS treatment through increasing ANG expression or angiogenin activity. However, the related study is still in its infancy; therefore, this article also highlights the need for further exploration of the application of ANG gene mutations in clinical trials and animal experiments is needed to achieve improved early diagnosis and treatment of ALS.}, } @article {pmid38421467, year = {2024}, author = {Zhong, X and Li, C and Li, Y and Huang, Y and Liu, J and Jiang, A and Chen, J and Peng, Y}, title = {IRAK-M Plays A Role in the Pathology of Amyotrophic Lateral Sclerosis Through Suppressing the Activation of Microglia.}, journal = {Molecular neurobiology}, volume = {61}, number = {10}, pages = {7603-7610}, pmid = {38421467}, issn = {1559-1182}, support = {81901239//National Natural Science Foundation of China/ ; 82171354//National Natural Science Foundation of China/ ; 202201010924//Science and Technology Projects in Guangzhou/ ; }, mesh = {Animals ; *Amyotrophic Lateral Sclerosis/pathology/metabolism/genetics ; *Microglia/metabolism/pathology ; *Interleukin-1 Receptor-Associated Kinases/metabolism/genetics ; *Mice, Transgenic ; *Spinal Cord/pathology/metabolism ; Motor Neurons/pathology/metabolism ; Dependovirus/genetics ; Mice ; RNA, Messenger/metabolism/genetics ; Interleukin-1beta/metabolism ; Disease Models, Animal ; Mice, Inbred C57BL ; Humans ; Superoxide Dismutase-1/genetics/metabolism ; }, abstract = {Microglial activation plays a crucial role in the disease progression in amyotrophic lateral sclerosis (ALS). Interleukin receptor-associated kinases-M (IRAK-M) is an important negative regulatory factor in the Toll-like receptor 4 (TLR4) pathway during microglia activation, and its mechanism in this process is still unclear. In the present study, we aimed to investigate the dynamic changes of IRAK-M and its protective effects for motor neurons in SOD1-G93A mouse model of ALS. qPCR (Real-time Quantitative PCR Detecting System) were used to examine the mRNA levels of IRAK-M in the spinal cord in both SOD1-G93A mice and their age-matched wild type (WT) littermates at 60, 100 and 140 days of age. We established an adeno-associated virus 9 (AAV9)-based platform by which IRAK-M was targeted mostly to microglial cells to investigate whether this approach could provide a protection in the SOD1-G93A mouse. Compared with age-matched WT mice, IRAK-M mRNA level was elevated at 100 and 140 days in the anterior horn region of spinal cords in the SOD1-G93A mouse. AAV9-IRAK-M treated SOD1-G93A mice showed reduction of IL-1β mRNA levels and significant improvements in the numbers of spinal motor neurons in spinal cord. Mice also showed previously reduction of muscle atrophy. Our data revealed the dynamic changes of IRAK-M during ALS pathological progression and demonstrated that an AAV9-IRAK-M delivery was an effective and translatable therapeutic approach for ALS. These findings may help identify potential molecular targets for ALS therapy.}, } @article {pmid38418587, year = {2024}, author = {Thiry, L and Sirois, J and Durcan, TM and Stifani, S}, title = {Generation of human iPSC-derived phrenic-like motor neurons to model respiratory motor neuron degeneration in ALS.}, journal = {Communications biology}, volume = {7}, number = {1}, pages = {238}, pmid = {38418587}, issn = {2399-3642}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism ; *Induced Pluripotent Stem Cells/metabolism ; Motor Neurons/physiology ; Diaphragm ; *Respiration Disorders/metabolism ; Nerve Degeneration ; }, abstract = {The fatal motor neuron (MN) disease Amyotrophic Lateral Sclerosis (ALS) is characterized by progressive MN degeneration. Phrenic MNs (phMNs) controlling the activity of the diaphragm are prone to degeneration in ALS, leading to death by respiratory failure. Understanding of the mechanisms of phMN degeneration in ALS is limited, mainly because human experimental models to study phMNs are lacking. Here we describe a method enabling the derivation of phrenic-like MNs from human iPSCs (hiPSC-phMNs) within 30 days. This protocol uses an optimized combination of small molecules followed by cell-sorting based on a cell-surface protein enriched in hiPSC-phMNs, and is highly reproducible using several hiPSC lines. We show further that hiPSC-phMNs harbouring ALS-associated amplification of the C9orf72 gene progressively lose their electrophysiological activity and undergo increased death compared to isogenic controls. These studies establish a previously unavailable protocol to generate human phMNs offering a disease-relevant system to study mechanisms of respiratory MN dysfunction.}, } @article {pmid38418571, year = {2024}, author = {Kumar, S and Bhowmik, R and Oh, JM and Abdelgawad, MA and Ghoneim, MM and Al-Serwi, RH and Kim, H and Mathew, B}, title = {Machine learning driven web-based app platform for the discovery of monoamine oxidase B inhibitors.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {4868}, pmid = {38418571}, issn = {2045-2322}, mesh = {Humans ; Molecular Docking Simulation ; *Mobile Applications ; Monoamine Oxidase/metabolism ; Monoamine Oxidase Inhibitors/chemistry ; *Neurodegenerative Diseases/drug therapy ; Dopamine Agents/pharmacology ; Internet ; Structure-Activity Relationship ; }, abstract = {Monoamine oxidases (MAOs), specifically MAO-A and MAO-B, play important roles in the breakdown of monoamine neurotransmitters. Therefore, MAO inhibitors are crucial for treating various neurodegenerative disorders, including Parkinson's disease (PD), Alzheimer's disease (AD), and amyotrophic lateral sclerosis (ALS). In this study, we developed a novel cheminformatics pipeline by generating three diverse molecular feature-based machine learning-assisted quantitative structural activity relationship (ML-QSAR) models concerning MAO-B inhibition. PubChem fingerprints, substructure fingerprints, and one-dimensional (1D) and two-dimensional (2D) molecular descriptors were implemented to unravel the structural insights responsible for decoding the origin of MAO-B inhibition in 249 non-reductant molecules. Based on a random forest ML algorithm, the final PubChem fingerprint, substructure fingerprint, and 1D and 2D molecular descriptor prediction models demonstrated significant robustness, with correlation coefficients of 0.9863, 0.9796, and 0.9852, respectively. The significant features of each predictive model responsible for MAO-B inhibition were extracted using a comprehensive variance importance plot (VIP) and correlation matrix analysis. The final predictive models were further developed as a web application, MAO-B-pred (https://mao-b-pred.streamlit.app/), to allow users to predict the bioactivity of molecules against MAO-B. Molecular docking and dynamics studies were conducted to gain insight into the atomic-level molecular interactions between the ligand-receptor complexes. These findings were compared with the structural features obtained from the ML-QSAR models, which supported the mechanistic understanding of the binding phenomena. The presented models have the potential to serve as tools for identifying crucial molecular characteristics for the rational design of MAO-B target inhibitors, which may be used to develop effective drugs for neurodegenerative disorders.}, } @article {pmid38418214, year = {2024}, author = {Otani, R and Shibuya, K and Suzuki, YI and Suichi, T and Morooka, M and Aotsuka, Y and Ogushi, M and Kuwabara, S}, title = {Effects of motor cortical and peripheral axonal hyperexcitability on survival in amyotrophic lateral sclerosis.}, journal = {Journal of neurology, neurosurgery, and psychiatry}, volume = {95}, number = {8}, pages = {730-736}, doi = {10.1136/jnnp-2023-333039}, pmid = {38418214}, issn = {1468-330X}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology/mortality ; Male ; Female ; Middle Aged ; *Motor Cortex/physiopathology ; *Transcranial Magnetic Stimulation ; *Axons/physiology ; Aged ; Motor Neurons/physiology ; Evoked Potentials, Motor/physiology ; Adult ; Prognosis ; }, abstract = {BACKGROUND: Increased 'cortical' and 'peripheral' excitability are reportedly associated with shorter survival in amyotrophic lateral sclerosis (ALS) patients, suggesting that hyperexcitability contributes to motor neuron death. However, whether upper or lower motor function has a greater impact on survival is unclear. We aimed to investigate the component that strongly impacts the prognosis of ALS.

METHODS: A total of 103 consecutive patients with ALS who underwent cortical (threshold tracking transcranial magnetic stimulation (TMS)) and motor nerve excitability tests were included. Motor cortical excitability was evaluated using short-interval intracortical inhibition (SICI) during TMS. Motor axonal excitability was assessed using the strength-duration time constant (SDTC). Survival time was defined as the time from examination to death or tracheostomy.

RESULTS: Compared with healthy subjects, patients with ALS had lower SICI and longer SDTC (p<0.05), indicating increased excitability of cortical motor neurons and motor axons. According to the SICI and SDTC findings, patients were divided into the following four groups: 'cortical high and peripheral high (high-high)', 'high-low', 'low-high' and 'low-low' groups. In Kaplan-Meier curves, the 'high-high' and 'low-high' groups showed significantly shorter survival than the other groups. Multivariate analysis revealed that increased cortical (HR=5.3, p<0.05) and peripheral (HR=20.0, p<0.001) excitability were significantly associated with shorter survival.

CONCLUSIONS: In patients with ALS, both motor cortical and peripheral hyperexcitability independently affected survival time, with peripheral hyperexcitability having a greater impact on shorter survival. The modulation of neuronal/axonal excitability is a potential therapeutic target for ALS.}, } @article {pmid38417517, year = {2024}, author = {Li, M and Qiu, J and Yan, G and Zheng, X and Li, A}, title = {How does the neurotoxin β-N-methylamino-L-alanine exist in biological matrices and cause toxicity?.}, journal = {The Science of the total environment}, volume = {922}, number = {}, pages = {171255}, doi = {10.1016/j.scitotenv.2024.171255}, pmid = {38417517}, issn = {1879-1026}, mesh = {Animals ; Humans ; *Neurotoxins/chemistry ; *Amino Acids, Diamino/toxicity/chemistry ; Cyanobacteria Toxins ; Oxidative Stress ; }, abstract = {The neurotoxin β-N-methylamino-L-alanine (BMAA) has been deemed as a risk factor for some neurodegenerative diseases such as amyotrophic lateral sclerosis/parkinsonism dementia complex (ALS/PDC). This possible link has been proved in some primate models and cell cultures with the appearance that BMAA exposure can cause excitotoxicity, formation of protein aggregates, and/or oxidative stress. The neurotoxin BMAA extensively exists in the environment and can be transferred through the food web to human beings. In this review, the occurrence, toxicological mechanisms, and characteristics of BMAA were comprehensively summarized, and proteins and peptides were speculated as its possible binding substances in biological matrices. It is difficult to compare the published data from previous studies due to the inconsistent analytical methods and components of BMAA. The binding characteristics of BMAA should be focused on to improve our understanding of its health risk to human health in the future.}, } @article {pmid38417402, year = {2024}, author = {Hu, N and Soh, KL and Japar, S and Li, T}, title = {Ear-Marking Relief: A Meta-Analysis on the Efficacy of Auricular Acupressure in Alleviating Anxiety Disorders.}, journal = {Complementary medicine research}, volume = {31}, number = {3}, pages = {266-277}, doi = {10.1159/000537734}, pmid = {38417402}, issn = {2504-2106}, mesh = {Humans ; *Acupressure ; *Anxiety Disorders/therapy ; Randomized Controlled Trials as Topic ; Auriculotherapy/methods ; }, abstract = {BACKGROUND: The increasing worldwide mental health crisis, notably anxiety, emphasizes the urgency for available and effective interventions. Traditional therapies, although beneficial, pose limitations due to their considerable costs and possible adverse effects, thereby inviting alternative treatments such as auricular acupressure (AA). This non-pharmacological, integrative method, underpinned by Eastern and Western medical principles, presents a significant prospect for managing anxiety.

OBJECTIVE: This study aims to evaluate the existing evidence on the efficacy of AA in reducing anxiety, as elucidated through a systematic review.

METHODS: A comprehensive search of randomized controlled trials was conducted across various databases: the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, EMBASE, Web of Science, Chinese National Knowledge Infrastructure (CNKI), China Biology Medicine (CBM), Wan Fang, and Database for Chinese Technical Periodicals (VIP). Two reviewers retrieved the pertinent studies and assessed their methodological quality. A meta-analysis was then conducted, incorporating data from all relevant time points.

RESULTS: Upon examining 25 studies encompassing 1,909 participants, it was discerned that AA significantly diminished anxiety (SMD = -1.1074; 95% confidence interval, -1.348 to -0.801; z = 7.70, p < 0.01). Subgroup analyses indicated that neither an increased number of auricular points nor extended intervention augmented effects. Larger effect sizes were associated with probing and avoidance of sham acupressure. Notably, 23 of the 25 studies exhibited some bias, suggesting further research is necessary.

CONCLUSIONS: The extant evidence advocates for AA as an effective supplementary intervention that reduces patient anxiety. The results hint at a potential placebo effect elicited by sham acupressure, necessitating rigorous control group definitions in future inquiries. The study findings suggest that fewer acupressure points and shorter intervention durations could effectively alleviate anxiety symptoms. Nonetheless, the significant heterogeneity across the studies underscores the requirement for more stringent research methodologies to substantiate these conclusions.

UNLABELLED: HintergrundDie weltweit zunehmende Krise der psychischen Gesundheit, vor allem von Angstzuständen, zeigt, dass dringend verfügbare und wirksame Interventionen erforderlich sind. Herkömmliche Therapien sind zwar hilfreich, werden aber durch ihre hohen Kosten und möglichen unerwünschten Wirkungen eingeschränkt, so dass alternative Behandlungen wie die Ohrakupressur gefragt sind. Diese nicht-pharmakologische, integrative Methode, die sich auf östliche und westliche medizinische Prinzipien stützt, stellt eine bedeutsame Perspektive für die Behandlung von Angstzuständen dar.ZielZiel dieser Studie ist es, die vorhandenen Evidenzen für die Wirksamkeit der Ohrakupressur (auricular acupressure, AA) zur Verringerung von Angstzuständen, die in einer systematischen Übersichtsarbeit ermittelt wurden, zu bewerten.MethodenEs wurde eine umfassende Suche nach randomisierten kontrollierten Studien in verschiedenen Datenbanken durchgeführt: Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, EMBASE, Web of Science, Chinese National Knowledge Infrastructure (CNKI), China Biology Medicine (CBM), Wan Fang und Database for Chinese Technical Periodicals (VIP). Zwei Gutachter suchten die einschlägigen Studien heraus und bewerteten ihre methodische Qualität. Anschliessend erfolgte eine Metaanalyse, bei der Daten aller relevanten Zeitpunkte berücksichtigt wurden.Ergebnisse:Die Untersuchung von 25 Studien mit 1’909 Teilnehmern ergab, dass die Ohrakupressur (AA) Angstzustände signifikant verringerte (SMD = −1,1074; 95%-KI: −1,348 bis −0,801; z = 7,70, p < 0,01). Subgruppenanalysen zeigten, dass die Effekte weder durch eine höhere Anzahl von Ohrpunkten noch durch eine längere Intervention verstärkt wurden. Grössere Effektstärken waren mit Sondenverwendung und Vermeidung von Scheinakupressur assoziiert. Hervorzuheben ist, dass 23 der 25 Studien eine gewisse Verzerrung aufwiesen, weshalb weitere Untersuchungen erforderlich sind.SchlussfolgerungenDie vorhandene Evidenzlage stützt die Ohrakupressur (AA) als wirksame unterstützende Intervention, die die Angst der Patienten verringert. Die Ergebnisse deuten auf einen potenziellen Placeboeffekt durch Scheinakupressur hin, so dass in künftigen Untersuchungen strenge Kontrollgruppendefinitionen erforderlich sind. Die Studienergebnisse sprechen dafür, dass eine geringere Anzahl von Akupressurpunkten und kürzere Interventionszeiten die Angstsymptome wirksam lindern können. Die starke Heterogenität der Studien zeigt allerdings, dass strengere wissenschaftliche Methoden erforderlich sind, um diese Schlussfolgerungen zu untermauern.}, } @article {pmid38416402, year = {2024}, author = {Wolff, AW and Peine, J and Höfler, J and Zurek, G and Hemker, C and Lingor, P}, title = {SAFE-ROCK: A Phase I Trial of an Oral Application of the ROCK Inhibitor Fasudil to Assess Bioavailability, Safety, and Tolerability in Healthy Participants.}, journal = {CNS drugs}, volume = {38}, number = {4}, pages = {291-302}, pmid = {38416402}, issn = {1179-1934}, support = {2017_T05//Else Kröner-Fresenius-Stiftung/ForTra GmbH/ ; }, mesh = {Male ; Humans ; Female ; *rho-Associated Kinases ; Biological Availability ; Healthy Volunteers ; *Protein Kinase Inhibitors/adverse effects ; Chronic Disease ; Administration, Oral ; 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine/*analogs & derivatives ; }, abstract = {BACKGROUND: The intravenous (IV) formulation of Rho-kinase (ROCK) inhibitor fasudil has been approved for the treatment of subarachnoid haemorrhage since 1995. Additionally, fasudil has shown promising preclinical results for various chronic diseases, including neurodegenerative diseases such as amyotrophic lateral sclerosis, Parkinson's disease, and dementia, in which long-term intravenous (IV) administration might not be suitable.

OBJECTIVE: The objective of this study was to assess the absolute bioavailability of oral, in comparison to IV, application of the approved formulation of fasudil (ERIL®) and to evaluate the safety and tolerability of the oral application of fasudil.

METHODS: This was a phase I, single-center, open-label, randomized, two period cross-over clinical trial in healthy women and men. By applying a cross-over design, each subject served as their own control. Two treatments were investigated, separated by a wash out phase of at least 3 days. Oral fasudil was administered once on day 1 to assess pharmacokinetics and three times on day 2, at an interval of 8 ± 1 h, to assess safety and gastrointestinal tolerability. For pharmacometrics of IV fasudil, it was administered once on day 1. Plasma profiles of fasudil and its active metabolite hydroxyfasudil after oral or IV administration were measured by liquid chromatography electrospray tandem mass spectrometry. Tolerability was assessed as proportion of subjects without significant drug intolerance, and safety was assessed by the proportion of subjects without clinical or laboratory treatment-associated serious adverse events. Gastrointestinal safety was assessed by applying the gastrointestinal symptom rating scale (GSRS).

RESULTS: Fourteen subjects aged 30-70 years were included in this trial. After oral administration, fasudil concentrations in blood were mostly very low [1.4 g/L; coefficient of variation (CV) 41.0%]. After IV application, the peak concentration was 100.6 µg/L (CV 74.2%); however, a high variance in peak concentrations were assessed for both treatments. The maximal concentrations of hydroxyfasudil in blood were similar after oral and IV treatment [111.6 µg/L (CV 24.1%) and 108.4 µg/L (CV 19.7%), respectively]. Exposure of hydroxyfasudil (assessed as AUC0-tz) differed between both treatments, with 449 µg × h/L after IV treatment and 309 µg × h/L after oral treatment. Therefore, the absolute bioavailability of hydroxyfasudil after the oral treatment was approximately 69% of the IV treatment. No serious adverse events (SAEs) occurred during this trial, and good tolerability of oral fasudil (90 mg/day) was documented.

CONCLUSIONS: Oral fasudil was generally well tolerated in the studied population, and no safety concerns were identified. However, systemic bioavailability of oral hydroxyfasudil corresponded to 69%, and dose adjustments need to considered. The results presented here lay grounds for future trials of fasudil in chronic diseases, which require an oral long-term application. This trial was registered with EudraCT (no. 2019-001805-26).}, } @article {pmid38415696, year = {2024}, author = {Didcote, L and Vitoratou, S and Al-Chalabi, A and Goldstein, LH}, title = {What is the extent of reliability and validity evidence for screening tools for cognitive and behavioral change in people with ALS? A systematic review.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {25}, number = {5-6}, pages = {437-451}, pmid = {38415696}, issn = {2167-9223}, support = {MR/L501529/1/MRC_/Medical Research Council/United Kingdom ; MR/R024804/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/psychology/diagnosis/complications ; Reproducibility of Results ; Neuropsychological Tests/standards ; Cognitive Dysfunction/diagnosis/etiology ; }, abstract = {OBJECTIVE: This systematic review provides an updated summary of the existing literature on the validity of screening tools for cognitive and behavioral impairment in people with Amyotrophic Lateral Sclerosis (pwALS), and also focuses on their reliability.

METHOD: The following cognitive and behavioral screening tools were assessed in this review: the Edinburgh Cognitive and Behavioral ALS Screen (ECAS); the ALS Cognitive Behavioral Screen (ALS-CBS), the Mini Addenbrooke's Cognitive Examination (Mini-ACE), the Beaumont Behavioral Interview (BBI); the MND Behavior Scale (MiND-B); and the ALS-FTD Questionnaire (ALS-FTD-Q). A search, using Medline, PsychINFO and Embase (21/09/2023), generated 37 results after exclusion criteria were applied. Evidence of internal consistency, item-total correlations, inter-rater reliability, clinical validity, convergent validity, and structural validity were extracted and assessed and risk of bias was evaluated.

RESULTS: The cognitive component of the ECAS was the tool with most evidence of reliability and validity for the assessment of cognitive impairment in ALS. It is well-suited to accommodate physical symptoms of ALS. For behavioral assessment, the BBI or ALS-FTD-Q had the most evidence of reliability and validity. The BBI is more thorough, but the ALS-FTD-Q is briefer.

CONCLUSIONS: There is good but limited evidence for the reliability and validity of cognitive and behavioral screens. Further evidence of clinical and convergent validity would increase confidence in their clinical and research use.}, } @article {pmid38415587, year = {2024}, author = {Koehn, LM and Steele, JR and Schittenhelm, RB and Turner, BJ and Nicolazzo, JA}, title = {Sex-Dependent Changes to the Intestinal and Hepatic Abundance of Drug Transporters and Metabolizing Enzymes in the SOD1[G93A] Mouse Model of Amyotrophic Lateral Sclerosis.}, journal = {Molecular pharmaceutics}, volume = {21}, number = {4}, pages = {1756-1767}, doi = {10.1021/acs.molpharmaceut.3c01089}, pmid = {38415587}, issn = {1543-8392}, mesh = {Animals ; Female ; Humans ; Male ; Mice ; *Amyotrophic Lateral Sclerosis/genetics ; Disease Models, Animal ; Liver/metabolism ; Mice, Transgenic ; *Organic Anion Transporters/metabolism ; Proteomics ; Superoxide Dismutase/metabolism ; Superoxide Dismutase-1/genetics/metabolism ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is characterized by death and dysfunction of motor neurons that result in a rapidly progressing loss of motor function. While there are some data on alterations at the blood-brain barrier (BBB) in ALS and their potential impact on CNS trafficking of drugs, little is reported on the impact of this disease on the expression of drug-handling proteins in the small intestine and liver. This may impact the dosing of the many medicines that individuals with ALS are prescribed. In the present study, a proteomic evaluation was performed on small intestine and liver samples from postnatal day 120 SOD1[G93A] mice (a model of familial ALS that harbors a human mutant form of superoxide dismutase 1) and wild-type (WT) littermates (n = 7/genotype/sex). Untargeted, quantitative proteomics was undertaken using either label-based [tandem mass tag (TMT)] or label-free [data-independent acquisition (DIA)] acquisition strategies on high-resolution mass spectrometric instrumentation. Copper chaperone for superoxide dismutase (CCS) was significantly higher in SOD1[G93A] samples compared to the WT samples for both sexes and tissues, therefore representing a potential biomarker for ALS in this mouse model. Relative to WT mice, male SOD1[G93A] mice had significantly different proteins (Padj < 0.05, |fold-change|>1.2) in the small intestine (male 22, female 1) and liver (male 140, female 3). This included an up-regulation of intestinal transporters for dietary glucose [solute carrier (SLC) SLC5A1] and cholesterol (Niemann-Pick c1-like 1), as well as for several drugs (e.g., SLC15A1), in the male SOD1[G93A] mice. There was both an up-regulation (e.g., SLCO2A1) and down-regulation (ammonium transporter rh type b) of transporters in the male SOD1[G93A] liver. In addition, there was both an up-regulation (e.g., phosphoenolpyruvate carboxykinase) and down-regulation (e.g., carboxylesterase 1) of metabolizing enzymes in the male SOD1[G93A] liver. This proteomic data set identified male-specific changes to key small intestinal and hepatic transporters and metabolizing enzymes that may have important implications for the bioavailability of nutrients and drugs in individuals with ALS.}, } @article {pmid38414054, year = {2024}, author = {Ma, YY and Li, X and Yu, JT and Wang, YJ}, title = {Therapeutics for neurodegenerative diseases by targeting the gut microbiome: from bench to bedside.}, journal = {Translational neurodegeneration}, volume = {13}, number = {1}, pages = {12}, pmid = {38414054}, issn = {2047-9158}, support = {92249305//National Natural Science Foundation of China/ ; }, mesh = {Humans ; *Neurodegenerative Diseases/therapy ; *Gastrointestinal Microbiome ; *Amyotrophic Lateral Sclerosis ; *Alzheimer Disease ; *Parkinson Disease/therapy ; }, abstract = {The aetiologies and origins of neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and Huntington's disease (HD), are complex and multifaceted. A growing body of evidence suggests that the gut microbiome plays crucial roles in the development and progression of neurodegenerative diseases. Clinicians have come to realize that therapeutics targeting the gut microbiome have the potential to halt the progression of neurodegenerative diseases. This narrative review examines the alterations in the gut microbiome in AD, PD, ALS and HD, highlighting the close relationship between the gut microbiome and the brain in neurodegenerative diseases. Processes that mediate the gut microbiome-brain communication in neurodegenerative diseases, including the immunological, vagus nerve and circulatory pathways, are evaluated. Furthermore, we summarize potential therapeutics for neurodegenerative diseases that modify the gut microbiome and its metabolites, including diets, probiotics and prebiotics, microbial metabolites, antibacterials and faecal microbiome transplantation. Finally, current challenges and future directions are discussed.}, } @article {pmid38413232, year = {2024}, author = {Chun, C and Lee, JH and Bothwell, M and Nghiem, P and Smith, AST and Mack, DL}, title = {Human Motor Neurons Elicit Pathological Hallmarks of ALS and Reveal Potential Biomarkers of the Disease in Response to Prolonged IFNγ Exposure.}, journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, volume = {44}, number = {16}, pages = {}, pmid = {38413232}, issn = {1529-2401}, support = {P01 CA225517/CA/NCI NIH HHS/United States ; R03 TR004009/TR/NCATS NIH HHS/United States ; }, mesh = {Animals ; Humans ; Mice ; *Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology ; B7-H1 Antigen/metabolism ; Biomarkers ; DNA-Binding Proteins/genetics ; *Induced Pluripotent Stem Cells/metabolism ; Interferon-gamma/metabolism/pharmacology ; Motor Neurons/drug effects/metabolism/pathology ; Tumor Suppressor Protein p53/metabolism ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a debilitating neurodegenerative disorder marked by progressive motor neuron degeneration and muscle denervation. A recent transcriptomic study integrating a wide range of human ALS samples revealed that the upregulation of p53, a downstream target of inflammatory stress, is commonly detected in familial and sporadic ALS cases by a mechanism linked to a transactive response DNA-binding protein 43 (TDP-43) dysfunction. In this study, we show that prolonged interferon-gamma (IFNγ) treatment of human induced pluripotent stem cell-derived spinal motor neurons results in a severe cytoplasmic aggregation of TDP-43. TDP-43 dysfunction resulting from either IFNγ exposure or an ALS-associated TDP-43 mutation was associated with the activation of the p53 pathway. This was accompanied by the hyperactivation of neuronal firing, followed by the complete loss of their electrophysiological function. Through a comparative single-cell transcriptome analysis, we have identified significant alterations in ALS-associated genes in motor neurons exposed to IFNγ, implicating their direct involvement in ALS pathology. Interestingly, IFNγ was found to induce significant levels of programmed death-ligand 1 (PD-L1) expression in motor neurons without affecting the levels of any other immune checkpoint proteins. This finding suggests a potential role of excessive PD-L1 expression in ALS development, given that PD-L1 was recently reported to impair neuronal firing ability in mice. Our findings suggest that exposing motor neurons to IFNγ could directly derive ALS pathogenesis, even without the presence of the inherent genetic mutation or functional glia component. Furthermore, this study provides a comprehensive list of potential candidate genes for future immunotherapeutic targets with which to treat sporadic forms of ALS, which account for 90% of all reported cases.}, } @article {pmid38412787, year = {2024}, author = {Zhan, ZQ and Huang, ZM and Zhou, HB and Xie, ZX and Chen, YZ and Luo, YH and Chen, PZ and Kang, JQ and Cheng, ZJ and Sun, B}, title = {Gastroesophageal reflux disease with 6 neurodegenerative and psychiatric disorders: Genetic correlations, causality, and potential molecular mechanisms.}, journal = {Journal of psychiatric research}, volume = {172}, number = {}, pages = {244-253}, doi = {10.1016/j.jpsychires.2024.02.030}, pmid = {38412787}, issn = {1879-1379}, mesh = {Humans ; *Sleep Initiation and Maintenance Disorders ; *Depressive Disorder, Major/epidemiology/genetics ; *Mental Disorders/epidemiology/genetics ; Anxiety Disorders/epidemiology/genetics ; *Gastroesophageal Reflux/epidemiology/genetics ; Genome-Wide Association Study ; }, abstract = {The comorbidities between gastroesophageal reflux disease (GERD) and various neurodegenerative and psychiatric disorders have been widely reported. However, the genetic correlations, causal relationships, and underlying mechanisms linking GERD to these disorders remain largely unknown. Here, we conducted a bidirectional Mendelian randomization (MR) analysis to determine the causality between GERD and 6 neurodegenerative and psychiatric disorders. Sensitivity analyses and multivariable MR were performed to test the robustness of our findings. Linkage disequilibrium score regression was used to assess the genetic correlation between these diseases as affected by heredity. Multiple bioinformatics tools combining two machine learning algorithms were applied to further investigate the potential mechanisms underlying these diseases. We found that genetically predicted GERD significantly increased the risk of Alzheimer's disease, major depressive disorder, and anxiety disorders. There might be a bidirectional relationship between GERD and insomnia. GERD has varying degrees of genetic correlations with AD, ALS, anxiety disorders, insomnia, and depressive disorder. Bioinformatics analyses revealed the hub shared genes and the common pathways between GERD and 6 neurodegenerative and psychiatric disorders. Our findings demonstrated the complex nature of the genetic architecture across these diseases and clarified their causality, highlighting that treatments for the cure or remission of GERD may serve as potential strategies for preventing and managing neurodegenerative and psychiatric disorders.}, } @article {pmid38412259, year = {2024}, author = {Tseng, YJ and Krans, A and Malik, I and Deng, X and Yildirim, E and Ovunc, S and Tank, EMH and Jansen-West, K and Kaufhold, R and Gomez, NB and Sher, R and Petrucelli, L and Barmada, SJ and Todd, PK}, title = {Ribosomal quality control factors inhibit repeat-associated non-AUG translation from GC-rich repeats.}, journal = {Nucleic acids research}, volume = {52}, number = {10}, pages = {5928-5949}, pmid = {38412259}, issn = {1362-4962}, support = {//Alzheimer's Association Research Fellowship/ ; RF1 AG062077/AG/NIA NIH HHS/United States ; BX004842//VA BLRD/ ; I01 BX004842/BX/BLRD VA/United States ; R01 NS099280/NS/NINDS NIH HHS/United States ; //Cellular and Molecular Biology Graduate Program, University of Michigan/ ; R35 NS097273/NS/NINDS NIH HHS/United States ; P50HD104463/GF/NIH HHS/United States ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/metabolism ; Ataxia ; *C9orf72 Protein/genetics/metabolism ; DNA Repeat Expansion/genetics ; Fragile X Mental Retardation Protein/genetics/metabolism ; Fragile X Syndrome/genetics/metabolism ; *Frontotemporal Dementia/genetics/metabolism ; GC Rich Sequence ; HEK293 Cells ; Induced Pluripotent Stem Cells/metabolism ; Neurons/metabolism ; *Protein Biosynthesis ; Ribosomes/metabolism/genetics ; Tremor ; *Trinucleotide Repeat Expansion/genetics ; *Ribosomal Proteins/metabolism ; }, abstract = {A GGGGCC (G4C2) hexanucleotide repeat expansion in C9ORF72 causes amyotrophic lateral sclerosis and frontotemporal dementia (C9ALS/FTD), while a CGG trinucleotide repeat expansion in FMR1 leads to the neurodegenerative disorder Fragile X-associated tremor/ataxia syndrome (FXTAS). These GC-rich repeats form RNA secondary structures that support repeat-associated non-AUG (RAN) translation of toxic proteins that contribute to disease pathogenesis. Here we assessed whether these same repeats might trigger stalling and interfere with translational elongation. We find that depletion of ribosome-associated quality control (RQC) factors NEMF, LTN1 and ANKZF1 markedly boost RAN translation product accumulation from both G4C2 and CGG repeats while overexpression of these factors reduces RAN production in both reporter assays and C9ALS/FTD patient iPSC-derived neurons. We also detected partially made products from both G4C2 and CGG repeats whose abundance increased with RQC factor depletion. Repeat RNA sequence, rather than amino acid content, is central to the impact of RQC factor depletion on RAN translation-suggesting a role for RNA secondary structure in these processes. Together, these findings suggest that ribosomal stalling and RQC pathway activation during RAN translation inhibits the generation of toxic RAN products. We propose augmenting RQC activity as a therapeutic strategy in GC-rich repeat expansion disorders.}, } @article {pmid38411425, year = {2024}, author = {D'Urso, B and Weil, R and Génin, P}, title = {[Optineurin and mitochondrial dysfunction in neurodegeneration].}, journal = {Medecine sciences : M/S}, volume = {40}, number = {2}, pages = {167-175}, doi = {10.1051/medsci/2023220}, pmid = {38411425}, issn = {1958-5381}, mesh = {Humans ; Ubiquitin ; *Amyotrophic Lateral Sclerosis/genetics ; Cytosol ; Mitochondria/genetics ; *Mitochondrial Diseases ; }, abstract = {Optineurin (OPTN) is a multifunctional protein playing a crucial role as a receptor in selective autophagy. OPTN gene mutations are linked to diseases such as normal-tension glaucoma and amyotrophic lateral sclerosis. Recognized as a critical receptor for mitophagy, OPTN is pivotal in selectively degrading damaged mitochondria. This process is essential to prevent their accumulation, the generation of reactive oxygen species, and the release of pro-apoptotic factors. Mitophagy's quality control is governed by the PINK1 kinase and the cytosolic ubiquitin ligase Parkin, whose mutations are associated with Parkinson's disease. This review highlights recent insights emphasizing OPTN's role in mitophagy and its potential involvement in neurodegenerative diseases.}, } @article {pmid38411261, year = {2024}, author = {Sakowski, SA and Koubek, EJ and Chen, KS and Goutman, SA and Feldman, EL}, title = {Role of the Exposome in Neurodegenerative Disease: Recent Insights and Future Directions.}, journal = {Annals of neurology}, volume = {95}, number = {4}, pages = {635-652}, pmid = {38411261}, issn = {1531-8249}, support = {R01TS000327/CC/CDC HHS/United States ; R01 TS000327/TS/ATSDR CDC HHS/United States ; K23 ES027221/ES/NIEHS NIH HHS/United States ; R01 ES030049/ES/NIEHS NIH HHS/United States ; R01TS000289/CC/CDC HHS/United States ; R01 NS127188/NS/NINDS NIH HHS/United States ; R01 TS000289/TS/ATSDR CDC HHS/United States ; R01TS000289/ACL/ACL HHS/United States ; R01NS127188/NH/NIH HHS/United States ; R01ES030049/NH/NIH HHS/United States ; P30 DK020572/DK/NIDDK NIH HHS/United States ; K23ES027221/NH/NIH HHS/United States ; }, mesh = {Humans ; *Neurodegenerative Diseases/genetics ; *Exposome ; *Alzheimer Disease/genetics ; *Parkinson Disease/genetics ; }, abstract = {Neurodegenerative diseases are increasing in prevalence and place a significant burden on society. The causes are multifactorial and complex, and increasing evidence suggests a dynamic interplay between genes and the environment, emphasizing the importance of identifying and understanding the role of lifelong exposures, known as the exposome, on the nervous system. This review provides an overview of recent advances toward defining neurodegenerative disease exposomes, focusing on Parkinson's disease, amyotrophic lateral sclerosis, and Alzheimer's disease. We present the current state of the field based on emerging data, elaborate on key themes and potential mechanisms, and conclude with limitations and future directions. ANN NEUROL 2024;95:635-652.}, } @article {pmid38410712, year = {2024}, author = {Moretti, A and Pietersen, PI and Hassan, M and Shafiek, H and Prosch, H and Tarnoki, AD and Annema, JT and Munavvar, M and Bonta, PI and de Wever, W and Juul, AD}, title = {ERS International Congress 2023: highlights from the Clinical Techniques, Imaging and Endoscopy Assembly.}, journal = {ERJ open research}, volume = {10}, number = {1}, pages = {}, pmid = {38410712}, issn = {2312-0541}, abstract = {The Clinical Techniques, Imaging and Endoscopy Assembly is involved in the diagnosis and treatment of several pulmonary diseases, as demonstrated at the 2023 European Respiratory Society (ERS) International Congress in Milan, Italy. From interventional pulmonology, the congress included several exciting results for the use of bronchoscopy in lung cancer, including augmented fluoroscopy, robotic-assisted bronchoscopy and cryobiopsies. In obstructive lung disease, the latest results on bronchoscopic treatment of emphysema with hyperinflation and chronic bronchitis were presented. Research on using cryobiopsies to diagnose interstitial lung disease was further explored, with the aims of elevating diagnostic yield and minimising risk. For imaging, the latest updates in using artificial intelligence to overcome the increased workload of radiologists were of great interest. Novel imaging in sarcoidosis explored the use of magnetic resonance imaging, photon-counting computed tomography and positron emission tomography/computed tomography in the diagnostic work-up. Lung cancer screening is still a hot topic and new results were presented regarding incorporation of biomarkers, identifying knowledge gaps and improving screening programmes. The use of ultrasound in respiratory medicine is an expanding field, which was demonstrated by the large variety in studies presented at the 2023 ERS Congress. Ultrasound of the diaphragm in patients with amyotrophic lateral sclerosis and myasthenia gravis was used to assess movements and predict respiratory fatigue. Furthermore, studies using ultrasound to diagnose or monitor pulmonary disease were presented. The congress also included studies regarding the training and assessment of competencies as an important part of implementing ultrasound in clinical practice.}, } @article {pmid38409777, year = {2024}, author = {Rabadi, MH and Russell, KC and Xu, C}, title = {Predictors of Mortality in Veterans with Amyotrophic Lateral Sclerosis: Respiratory Status and Speech Disorder at Presentation.}, journal = {Medical science monitor : international medical journal of experimental and clinical research}, volume = {30}, number = {}, pages = {e943288}, pmid = {38409777}, issn = {1643-3750}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis ; Speech ; Dysarthria ; *Veterans ; Disease Progression ; }, abstract = {BACKGROUND There is a lack of accurate models to predict amyotrophic lateral sclerosis (ALS) disease course and outcomes. As a result, risk assessment and counseling, the timing of interventions, and their stratification in clinical trials are difficult. This study aimed to evaluate the association between symptoms at presentation and mortality. MATERIAL AND METHODS A single veterans hospital reviewed the electronic records of 105 veterans with ALS who were periodically followed in our ALS clinic between 2010 and 2021. A survival decision tree (≤3 or >3 years) was generated based on the statistical median survival of our data. The variables known to influence survival when alive were compared to patients who died. RESULTS The (mean±SD) age at onset was 62±11 years, M/F ratio 101: 4, and 90% were non-Hispanic whites. The initial score for the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) was 31±8.3. Dysarthria and shortness of breath (SOB) were present on initial presentation in 52 (49.5%) and 32 (30.5%) patients, respectively. Deaths occurred in 80 (76.2%) patients during the study period. The main cause of death was respiratory disease (failure and pneumonia, n=43 53.75%). Patients survived for >3 years on initial presentation with normal respiration and speech, compared to ≤3 years of survival in patients with dysarthria and SOB, irrespective of age. CONCLUSIONS This study suggests that for veterans with ALS, the main predictors of shorter survival were respiratory status and speech disorder on initial presentation to the clinic.}, } @article {pmid38409193, year = {2024}, author = {Chang, HY and Wang, IF}, title = {Restoring functional TDP-43 oligomers in ALS and laminopathic cellular models through baicalein-induced reconfiguration of TDP-43 aggregates.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {4620}, pmid = {38409193}, issn = {2045-2322}, support = {ND-01-003//Garage Brain Science/ ; ND-01-003//Garage Brain Science/ ; TDP-01//YeeFan Med Inc./ ; TDP-01//YeeFan Med Inc./ ; }, mesh = {Humans ; *Progeria/genetics ; Lamin Type A/genetics ; *Aging, Premature ; DNA-Binding Proteins/genetics ; *Flavanones ; }, abstract = {A group of misfolded prone-to-aggregate domains in disease-causing proteins has recently been shown to adopt unique conformations that play a role in fundamental biological processes. These processes include the formation of membrane-less sub-organelles, alternative splicing, and gene activation and silencing. The cellular responses are regulated by the conformational switching of prone-to-aggregate domains, independently of changes in RNA or protein expression levels. Given this, targeting the misfolded states of disease-causing proteins to redirect them towards their physiological conformations is emerging as an effective therapeutic strategy for diseases caused by protein misfolding. In our study, we successfully identified baicalein as a potent structure-correcting agent. Our findings demonstrate that baicalein can reconfigure existing TDP-43 aggregates into an oligomeric state both in vitro and in disease cells. This transformation effectively restores the bioactivity of misfolded TDP-43 proteins in cellular models of ALS and premature aging in progeria. Impressively, in progeria cells where defective lamin A interferes with TDP-43-mediated exon skipping, the formation of pathological TDP-43 aggregates is promoted. Baicalein, however, restores the functionality of TDP-43 and mitigates nuclear shape defects in these laminopathic cells. This establishes a connection between lamin A and TDP-43 in the context of aging. Our findings suggest that targeting physiological TDP-43 oligomers could offer a promising therapeutic avenue for treating aging-associated disorders.}, } @article {pmid38408864, year = {2024}, author = {Odierna, GL and Vucic, S and Dyer, M and Dickson, T and Woodhouse, A and Blizzard, C}, title = {How do we get from hyperexcitability to excitotoxicity in amyotrophic lateral sclerosis?.}, journal = {Brain : a journal of neurology}, volume = {147}, number = {5}, pages = {1610-1621}, pmid = {38408864}, issn = {1460-2156}, support = {//Motor Neuron Disease Research Australia/ ; //National Health and Medical Research Council of Australia/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/physiopathology ; Humans ; *Motor Neurons/physiology ; *Glutamic Acid/metabolism ; Animals ; Motor Cortex/physiopathology ; }, abstract = {Amyotrophic lateral sclerosis is a devastating neurodegenerative disease that, at present, has no effective cure. Evidence of increased circulating glutamate and hyperexcitability of the motor cortex in patients with amyotrophic lateral sclerosis have provided an empirical support base for the 'dying forward' excitotoxicity hypothesis. The hypothesis postulates that increased activation of upper motor neurons spreads pathology to lower motor neurons in the spinal cord in the form of excessive glutamate release, which triggers excitotoxic processes. Many clinical trials have focused on therapies that target excitotoxicity via dampening neuronal activation, but not all are effective. As such, there is a growing tension between the rising tide of evidence for the 'dying forward' excitotoxicity hypothesis and the failure of therapies that target neuronal activation. One possible solution to these contradictory outcomes is that our interpretation of the current evidence requires revision in the context of appreciating the complexity of the nervous system and the limitations of the neurobiological assays we use to study it. In this review we provide an evaluation of evidence relevant to the 'dying forward' excitotoxicity hypothesis and by doing so, identify key gaps in our knowledge that need to be addressed. We hope to provide a road map from hyperexcitability to excitotoxicity so that we can better develop therapies for patients suffering from amyotrophic lateral sclerosis. We conclude that studies of upper motor neuron activity and their synaptic output will play a decisive role in the future of amyotrophic lateral sclerosis therapy.}, } @article {pmid38408684, year = {2024}, author = {Dithmar, S and Zare, A and Salehi, S and Briese, M and Sendtner, M}, title = {hnRNP R regulates mitochondrial movement and membrane potential in axons of motoneurons.}, journal = {Neurobiology of disease}, volume = {193}, number = {}, pages = {106454}, doi = {10.1016/j.nbd.2024.106454}, pmid = {38408684}, issn = {1095-953X}, mesh = {Membrane Potentials ; *Motor Neurons/metabolism ; *Axons/pathology ; Heterogeneous-Nuclear Ribonucleoproteins/genetics/metabolism ; Mitochondria/metabolism ; }, abstract = {Axonal mitochondria defects are early events in the pathogenesis of motoneuron disorders such as spinal muscular atrophy and amyotrophic lateral sclerosis. The RNA-binding protein hnRNP R interacts with different motoneuron disease-related proteins such as SMN and TDP-43 and has important roles in axons of motoneurons, including axonal mRNA transport. However, whether hnRNP R also modulates axonal mitochondria is currently unknown. Here, we show that axonal mitochondria exhibit altered function and motility in hnRNP R-deficient motoneurons. Motoneurons lacking hnRNP R show decreased anterograde and increased retrograde transport of mitochondria in axons. Furthermore, hnRNP R-deficiency leads to mitochondrial hyperpolarization, caused by decreased complex I and reversed complex V activity within the respiratory chain. Taken together, our data indicate a role for hnRNP R in regulating transport and maintaining functionality of axonal mitochondria in motoneurons.}, } @article {pmid38405340, year = {2024}, author = {Sun, W and Wei, C}, title = {Causal Relationship Between Ferritin and Neuropsychiatric Disorders: A Two-Sample Mendelian Randomization Study.}, journal = {Journal of Alzheimer's disease reports}, volume = {8}, number = {1}, pages = {257-266}, pmid = {38405340}, issn = {2542-4823}, abstract = {BACKGROUND: Previous observational research has indicated a correlation between ferritin levels and neuropsychiatric disorders, although the causal relationship remains uncertain.

OBJECTIVE: The objective of this study was to investigate the potential causal link between plasma ferritin levels and neuropsychiatric disorders.

METHODS: A two-sample Mendelian randomization (MR) study was conducted, wherein genetic instruments associated with ferritin were obtained from a previously published genome-wide association study (GWAS). Summary statistics pertaining to neuropsychiatric disorders were derived from five distinct GWAS datasets. The primary MR analysis employed the inverse variance weighted (IVW) method and was corroborated by additional methods including MR-Egger, weighted median, simple mode, and weighted mode. Sensitivity analyses were employed to identify potential pleiotropy and heterogeneity in the results.

RESULTS: The fixed effects IVW method revealed a statistically significant causal relationship between plasma ferritin level and the occurrence of Alzheimer's disease (odds ratio [OR] = 1.06, 95% confidence interval [CI]: 1.00-1.12, p = 0.037), as well as Parkinson's disease (OR = 1.06, 95% CI: 1.00-1.13, p = 0.041). Various sensitivity analyses were conducted, which demonstrated no substantial heterogeneity or pleiotropy. Conversely, no compelling evidence was found to support a causal association between ferritin and amyotrophic lateral sclerosis, schizophrenia, or major depressive disorder.

CONCLUSIONS: This MR study provides evidence at the genetic level for a causal relationship between plasma ferritin and an increased risk of Alzheimer's disease and Parkinson's disease. The exact genetic mechanisms underlying this connection necessitate further investigation.}, } @article {pmid38405076, year = {2024}, author = {Dittlau, KS and Chandrasekaran, A and Freude, K and Van Den Bosch, L}, title = {Generation of Human Induced Pluripotent Stem Cell (hiPSC)-Derived Astrocytes for Amyotrophic Lateral Sclerosis and Other Neurodegenerative Disease Studies.}, journal = {Bio-protocol}, volume = {14}, number = {4}, pages = {e4936}, pmid = {38405076}, issn = {2331-8325}, abstract = {Astrocytes are increasingly recognized for their important role in neurodegenerative diseases like amyotrophic lateral sclerosis (ALS). In ALS, astrocytes shift from their primary function of providing neuronal homeostatic support towards a reactive and toxic role, which overall contributes to neuronal toxicity and cell death. Currently, our knowledge on these processes is incomplete, and time-efficient and reproducible model systems in a human context are therefore required to understand and therapeutically modulate the toxic astrocytic response for future treatment options. Here, we present an efficient and straightforward protocol to generate human induced pluripotent stem cell (hiPSC)-derived astrocytes implementing a differentiation scheme based on small molecules. Through an initial 25 days, hiPSCs are differentiated into astrocytes, which are matured for 4+ weeks. The hiPSC-derived astrocytes can be cryopreserved at every passage during differentiation and maturation. This provides convenient pauses in the protocol as well as cell banking opportunities, thereby limiting the need to continuously start from hiPSCs. The protocol has already proven valuable in ALS research but can be adapted to any desired research field where astrocytes are of interest. Key features • This protocol requires preexisting experience in hiPSC culturing for a successful outcome. • The protocol relies on a small molecule differentiation scheme and an easy-to-follow methodology, which can be paused at several time points. • The protocol generates >50 × 10[6] astrocytes per differentiation, which can be cryopreserved at every passage, ensuring a large-scale experimental output.}, } @article {pmid38404827, year = {2024}, author = {Liu, Y and Chang, Y and Jiang, X and Mei, H and Cao, Y and Wu, D and Xie, R and Jiang, W and Vasquez, E and Wu, Y and Lin, S and Cao, Y}, title = {Analysis of the role of PANoptosis in seizures via integrated bioinformatics analysis and experimental validation.}, journal = {Heliyon}, volume = {10}, number = {4}, pages = {e26219}, pmid = {38404827}, issn = {2405-8440}, abstract = {BACKGROUND: Epilepsy is recognized as the most common chronic neurological condition among children, and hippocampal neuronal cell death has been identified as a crucial factor in the pathophysiological processes underlying seizures. In recent studies, PANoptosis, a newly characterized form of cell death, has emerged as a significant contributor to the development of various neurological disorders, including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. PANoptosis involves the simultaneous activation of pyroptosis, apoptosis, and necroptosis within the same population of cells. However, its specific role in the context of seizures remains to be fully elucidated. Further investigation is required to uncover the precise involvement of PANoptosis in the pathogenesis of seizures and to better understand its potential implications for the development of targeted therapeutic approaches in epilepsy.

METHODS: In this study, the gene expression data of the hippocampus following the administration of kainic acid (KA) or NaCl was obtained from the Gene Expression Omnibus (GEO) database. The PANoptosis-related gene set was compiled from the GeneCards database and previous literature. Time series analysis was performed to analyze the temporal expression patterns of the PANoptosis-related genes. Gene set variation analysis (GSVA), Gene ontology (GO), and Kyoto encyclopedia of genes and genomes (KEGG) were employed to explore potential biological mechanisms underlying PANoptosis and its role in seizures. Weighted gene co-expression network analysis (WGCNA) and differential expression analysis were utilized to identify pivotal gene modules and PANoptosis-related genes associated with the pathophysiological processes underlying seizures. To validate the expression of PANoptosis-related genes, Western blotting or quantitative real-time polymerase chain reaction (qRT-PCR) assays were conducted. These experimental validations were performed in human blood samples, animal models, and cell models to verify the expression patterns of the PANoptosis-related genes and their relevance to epilepsy.

RESULTS: The GSVA analysis performed in this study demonstrated that PANoptosis-related genes have the potential to distinguish between the control group and KA-induced epileptic mice. This suggests that the expression patterns of these genes are significantly altered in response to KA-induced epilepsy. Furthermore, the Weighted gene co-expression network analysis (WGCNA) identified the blue module as being highly associated with epileptic phenotypes. This module consists of genes that exhibit correlated expression patterns specifically related to epilepsy. Within the blue module, 10 genes were further identified as biomarker genes for epilepsy. These genes include MLKL, IRF1, RIPK1, GSDMD, CASP1, CASP8, ZBP1, CASP6, PYCARD, and IL18. These genes likely play critical roles in the pathophysiology of epilepsy and could serve as potential biomarkers for diagnosing or monitoring the condition.

CONCLUSION: In conclusion, our study suggests that the hippocampal neuronal cell death in epilepsy may be closely related to PANoptosis, a novel form of cell death, which provides insights into the underlying pathophysiological processes of epilepsy and helps the development of novel therapeutic approaches for epilepsy.}, } @article {pmid38404440, year = {2024}, author = {Lee, SH and Pham, D and Kosa, E and Agbas, A}, title = {Human Platelet Derived Mitochondrial OPA-1 Isoforms and Interaction With TDP-43 in Neurodegenerative Diseases.}, journal = {Missouri medicine}, volume = {121}, number = {1}, pages = {87-92}, pmid = {38404440}, issn = {0026-6620}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism ; DNA, Mitochondrial/genetics/metabolism ; *DNA-Binding Proteins/genetics/metabolism ; Mitochondria/genetics/metabolism ; *Neurodegenerative Diseases/metabolism ; Protein Isoforms/metabolism ; *GTP Phosphohydrolases/genetics/metabolism ; }, abstract = {Optic atrophy 1(OPA1) is a GTPase protein that controls mitochondrial fusion, cristae integrity, and mtDNA maintenance. In neurodegenerative diseases such as Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), the mitochondrial network morphology is compromised. Studies on TAR-DNA binding protein 43 (TDP-43) has been the focus in our lab. OPA1 and TDP-43 interaction may shed a light on how aberrant TDP-43 interacts with OPA1, which will lead to mitochondrial dysfunction. The preliminary study tested the idea of whether OPA1 and TDP-43 are physically interacting in human platelet derived mitochondria obtained from healthy human subjects.}, } @article {pmid38404316, year = {2024}, author = {Dunn, KJ and Matlock, A and Funkenbusch, G and Yaqoob, Z and So, PTC and Berger, AJ}, title = {Optical diffraction tomography for assessing single cell models in angular light scattering.}, journal = {Biomedical optics express}, volume = {15}, number = {2}, pages = {973-990}, pmid = {38404316}, issn = {2156-7085}, abstract = {Angularly resolved light scattering (ALS) has become a useful tool for assessing the size and refractive index of biological scatterers at cellular and organelle length scales. Sizing organelle populations with ALS relies on Mie scattering theory models, which require significant assumptions about the object, including spherical scatterers and a homogeneous medium. These assumptions may incur greater error at the single cell level, where there are fewer scatterers to be averaged over. We investigate the validity of these assumptions using 3D refractive index (RI) tomograms measured via optical diffraction tomography (ODT). We compute the angular scattering on digitally manipulated tomograms with increasingly strong model assumptions, including RI-matched immersion media, homogeneous cytosol, and spherical organelles. We also compare the tomogram-computed angular scattering to experimental measurements of angular scattering from the same cells to ensure that the ODT-based approach accurately models angular scattering. We show that enforced RI-matching with the immersion medium and a homogeneous cytosol significantly affects the angular scattering intensity shape, suggesting that these assumptions can reduce the accuracy of size distribution estimates.}, } @article {pmid38403672, year = {2024}, author = {Wang, H and Chen, N and Jian, F and Zhang, Z and Tai, H and Pan, H}, title = {Amyotrophic lateral sclerosis and myasthenia gravis overlaps syndrome: a series of case report.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {45}, number = {7}, pages = {3549-3553}, pmid = {38403672}, issn = {1590-3478}, mesh = {Humans ; *Myasthenia Gravis/diagnosis/complications ; *Amyotrophic Lateral Sclerosis/complications/diagnosis ; Middle Aged ; Male ; Female ; Aged ; }, } @article {pmid38403286, year = {2024}, author = {Fan, H and Zhang, M and Wen, J and Wang, S and Yuan, M and Sun, H and Shu, L and Yang, X and Pu, Y and Cai, Z}, title = {Microglia in brain aging: An overview of recent basic science and clinical research developments.}, journal = {Journal of biomedical research}, volume = {38}, number = {2}, pages = {122-136}, pmid = {38403286}, issn = {1674-8301}, abstract = {Aging is characterized by progressive degeneration of tissues and organs, and it is positively associated with an increased mortality rate. The brain, as one of the most significantly affected organs, experiences age-related changes, including abnormal neuronal activity, dysfunctional calcium homeostasis, dysregulated mitochondrial function, and increased levels of reactive oxygen species. These changes collectively contribute to cognitive deterioration. Aging is also a key risk factor for neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease. For many years, neurodegenerative disease investigations have primarily focused on neurons, with less attention given to microglial cells. However, recently, microglial homeostasis has emerged as an important mediator in neurological disease pathogenesis. Here, we provide an overview of brain aging from the perspective of the microglia. In doing so, we present the current knowledge on the correlation between brain aging and the microglia, summarize recent progress of investigations about the microglia in normal aging, Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis, and then discuss the correlation between the senescent microglia and the brain, which will culminate with a presentation of the molecular complexity involved in the microglia in brain aging with suggestions for healthy aging.}, } @article {pmid38402886, year = {2024}, author = {Baudin, E and Goichot, B and Berruti, A and Hadoux, J and Moalla, S and Laboureau, S and Nölting, S and de la Fouchardière, C and Kienitz, T and Deutschbein, T and Zovato, S and Amar, L and Haissaguerre, M and Timmers, H and Niccoli, P and Faggiano, A and Angokai, M and Lamartina, L and Luca, F and Cosentini, D and Hahner, S and Beuschlein, F and Attard, M and Texier, M and Fassnacht, M and , and , }, title = {Sunitinib for metastatic progressive phaeochromocytomas and paragangliomas: results from FIRSTMAPPP, an academic, multicentre, international, randomised, placebo-controlled, double-blind, phase 2 trial.}, journal = {Lancet (London, England)}, volume = {403}, number = {10431}, pages = {1061-1070}, doi = {10.1016/S0140-6736(23)02554-0}, pmid = {38402886}, issn = {1474-547X}, mesh = {Adult ; Humans ; Adolescent ; Sunitinib/therapeutic use ; *Pheochromocytoma/drug therapy/etiology ; Progression-Free Survival ; *Hypertension/etiology ; *Adrenal Gland Neoplasms/drug therapy/etiology ; Double-Blind Method ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; }, abstract = {BACKGROUND: No randomised controlled trial has ever been done in patients with metastatic phaeochromocytomas and paragangliomas. Preclinical and first clinical evidence suggested beneficial effects of sunitinib. We aimed to evaluate the safety and efficacy of sunitinib in patients with metastatic phaeochromocytomas and paragangliomas.

METHODS: FIRSTMAPPP is a multicentre, international, randomised, placebo-controlled, double-blind, phase 2 trial done at 14 academic centres across four European countries. Eligible participants were adults (aged ≥18 years) with sporadic or inherited progressive metastatic phaeochromocytomas and paragangliomas. Patients were randomly assigned (1:1) to receive either oral sunitinib (37·5 mg per day) or placebo. Randomisation was stratified according to SDHB status (mutation present vs wild type) and number of previous systemic therapies (0 vs ≥1). Primary endpoint was the rate of progression-free survival at 12 months according to real-time central review (Response Evaluation Criteria in Solid Tumours version 1.1). On the basis of a two-step Simon model, we aimed for the accrual of 78 patients, assuming a 20% improvement of the 12-month progression-free survival rate from 20% to 40%, to conclude that sunitinib is effective. Crossover from the placebo group was allowed. This trial is registered with ClinicalTrials.gov, number NCT01371201, and is closed for enrolment.

FINDINGS: From Dec 1, 2011, to Jan 31, 2019, a total of 78 patients with progressive metastatic phaeochromocytomas and paragangliomas were enrolled (39 patients per group). 25 (32%) of 78 patients had germline SDHx variants and 54 (69%) had used previous therapies. The primary endpoint was met, with a 12-month progression-free survival in 14 of 39 patients (36% [90% CI 23-50]) in the sunitinib group. In the placebo group, the 12-month progression-free survival in seven of 39 patients was 19% (90% CI 11-31), validating the hypotheses of our study design. The most frequent grade 3 or 4 adverse events were asthenia (seven [18%] of 39 and one [3%] of 39), hypertension (five [13%] and four [10%]), and back or bone pain (one [3%] and three [8%]) in the sunitinib and placebo groups, respectively. Three deaths occurred in the sunitinib group: these deaths were due to respiratory insufficiency, amyotrophic lateral sclerosis, and rectal bleeding. Only the latter event was considered drug related. Two deaths occurred in the placebo group due to aspiration pneumonia and septic shock.

INTERPRETATION: This first randomised trial supports the use of sunitinib as the medical option with the highest level of evidence for anti-tumour efficacy in progressive metastatic phaeochromocytomas and paragangliomas.

FUNDING: French Ministry of Health, through the National Institute for Cancer, German Ministry of Education and Research, and the German Research Foundation within the CRC/Transregio 205/2, EU Seventh Framework Programme, and a private donator grant.}, } @article {pmid38401571, year = {2024}, author = {Cheng, F and Chapman, T and Zhang, S and Morsch, M and Chung, R and Lee, A and Rayner, SL}, title = {Understanding age-related pathologic changes in TDP-43 functions and the consequence on RNA splicing and signalling in health and disease.}, journal = {Ageing research reviews}, volume = {96}, number = {}, pages = {102246}, doi = {10.1016/j.arr.2024.102246}, pmid = {38401571}, issn = {1872-9649}, mesh = {Humans ; RNA Splicing ; *Amyotrophic Lateral Sclerosis/genetics/metabolism ; *Frontotemporal Dementia/genetics ; DNA-Binding Proteins/genetics/metabolism ; Neurons/metabolism ; }, abstract = {TAR DNA binding protein-43 (TDP-43) is a key component in RNA splicing which plays a crucial role in the aging process. In neurodegenerative diseases such as amyotrophic lateral sclerosis, frontotemporal dementia and limbic-predominant age-related TDP-43 encephalopathy, TDP-43 can be mutated, mislocalised out of the nucleus of neurons and glial cells and form cytoplasmic inclusions. These TDP-43 alterations can lead to its RNA splicing dysregulation and contribute to mis-splicing of various types of RNA, such as mRNA, microRNA, and circular RNA. These changes can result in the generation of an altered transcriptome and proteome within cells, ultimately changing the diversity and quantity of gene products. In this review, we summarise the findings of novel atypical RNAs resulting from TDP-43 dysfunction and their potential as biomarkers or targets for therapeutic development.}, } @article {pmid38401191, year = {2024}, author = {Lemon, R}, title = {The Corticospinal System and Amyotrophic Lateral Sclerosis: IFCN handbook chapter.}, journal = {Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology}, volume = {160}, number = {}, pages = {56-67}, doi = {10.1016/j.clinph.2024.02.001}, pmid = {38401191}, issn = {1872-8952}, mesh = {Animals ; Humans ; *Pyramidal Tracts/physiology ; *Amyotrophic Lateral Sclerosis ; Motor Neurons/physiology ; Primates ; Axons ; }, abstract = {Corticospinal neurons located in motor areas of the cerebral neocortex project corticospinal axons which synapse with the spinal network; a parallel corticobulbar system projects to the cranial motor network and to brainstem motor pathways. The primate corticospinal system has a widespread cortical origin and an extensive range of different fibre diameters, including thick, fast-conducting axons. Direct cortico-motoneuronal (CM) projections from the motor cortex to arm and hand alpha motoneurons are a recent evolutionary feature, that is well developed in dexterous primates and particularly in humans. Many of these projections originate from the caudal subdivision of area 4 ('new' M1: primary motor cortex). They arise from corticospinal neurons of varied soma size, including those with fast- and relatively slow-conducting axons. This CM system has been shown to be involved in the control of skilled movements, carried out with fractionation of the distal extremities and at low force levels. During movement, corticospinal neurons are activated quite differently from 'lower' motoneurons, and there is no simple or fixed functional relationship between a so-called 'upper' motoneuron and its target lower motoneuron. There are key differences in the organisation and function of the corticospinal and CM system in primates versus non-primates, such as rodents. These differences need to be recognized when making the choice of animal model for understanding disorders such as amyotrophic lateral sclerosis (ALS). In this neurodegenerative brain disease there is a selective loss of fast-conducting corticospinal axons, and their synaptic connections, and this is reflected in responses to non-invasive cortical stimuli and measures of cortico-muscular coherence. The loss of CM connections influencing distal limb muscles results in a differential loss of muscle strength or 'split-hand' phenotype. Importantly, there is also a unique impairment in the coordination of skilled hand tasks that require fractionation of digit movement. Scores on validated tests of skilled hand function could be used to assess disease progression.}, } @article {pmid38400897, year = {2024}, author = {Pirasteh, A and Shamseini Ghiyasvand, M and Pouladian, M}, title = {EEG-based brain-computer interface methods with the aim of rehabilitating advanced stage ALS patients.}, journal = {Disability and rehabilitation. Assistive technology}, volume = {19}, number = {8}, pages = {3183-3193}, doi = {10.1080/17483107.2024.2316312}, pmid = {38400897}, issn = {1748-3115}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/rehabilitation/physiopathology ; *Brain-Computer Interfaces ; *Electroencephalography ; Support Vector Machine ; Neural Networks, Computer ; }, abstract = {Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease that leads to progressive muscle weakness and paralysis, ultimately resulting in the loss of ability to communicate and control the environment. EEG-based Brain-Computer Interface (BCI) methods have shown promise in providing communication and control with the aim of rehabilitating ALS patients. In particular, P300-based BCI has been widely studied and used for ALS rehabilitation. Other EEG-based BCI methods, such as Motor Imagery (MI) based BCI and Hybrid BCI, have also shown promise in ALS rehabilitation. Nonetheless, EEG-based BCI methods hold great potential for improvement. This review article introduces and reviews FFT, WPD, CSP, CSSP, CSP, and GC feature extraction methods. The Common Spatial Pattern (CSP) is an efficient and common technique for extracting data properties used in BCI systems. In addition, Linear Discriminant Analysis (LDA), Support Vector Machine (SVM), Neural Networks (NN), and Deep Learning (DL) classification methods were introduced and reviewed. SVM is the most appropriate classifier due to its insensitivity to the curse of dimensionality. Also, DL is used in the design of BCI systems and is a good choice for BCI systems based on motor imagery with big datasets. Despite the progress made in the field, there are still challenges to overcome, such as improving the accuracy and reliability of EEG signal detection and developing more intuitive and user-friendly interfaces By using BCI, disabled patients can communicate with their caregivers and control their environment using various devices, including wheelchairs, and robotic arms.}, } @article {pmid38400247, year = {2024}, author = {Cano, LA and Albarracín, AL and Pizá, AG and García-Cena, CE and Fernández-Jover, E and Farfán, FD}, title = {Assessing Cognitive Workload in Motor Decision-Making through Functional Connectivity Analysis: Towards Early Detection and Monitoring of Neurodegenerative Diseases.}, journal = {Sensors (Basel, Switzerland)}, volume = {24}, number = {4}, pages = {}, pmid = {38400247}, issn = {1424-8220}, mesh = {Male ; Female ; Humans ; Young Adult ; Adult ; *Neurodegenerative Diseases/diagnosis ; Cerebral Cortex ; Muscle, Skeletal/physiology ; Electromyography ; Electroencephalography/methods ; Cognition ; }, abstract = {Neurodegenerative diseases (NDs), such as Alzheimer's, Parkinson's, amyotrophic lateral sclerosis, and frontotemporal dementia, among others, are increasingly prevalent in the global population. The clinical diagnosis of these NDs is based on the detection and characterization of motor and non-motor symptoms. However, when these diagnoses are made, the subjects are often in advanced stages where neuromuscular alterations are frequently irreversible. In this context, we propose a methodology to evaluate the cognitive workload (CWL) of motor tasks involving decision-making processes. CWL is a concept widely used to address the balance between task demand and the subject's available resources to complete that task. In this study, multiple models for motor planning during a motor decision-making task were developed by recording EEG and EMG signals in n=17 healthy volunteers (9 males, 8 females, age 28.66±8.8 years). In the proposed test, volunteers have to make decisions about which hand should be moved based on the onset of a visual stimulus. We computed functional connectivity between the cortex and muscles, as well as among muscles using both corticomuscular and intermuscular coherence. Despite three models being generated, just one of them had strong performance. The results showed two types of motor decision-making processes depending on the hand to move. Moreover, the central processing of decision-making for the left hand movement can be accurately estimated using behavioral measures such as planning time combined with peripheral recordings like EMG signals. The models provided in this study could be considered as a methodological foundation to detect neuromuscular alterations in asymptomatic patients, as well as to monitor the process of a degenerative disease.}, } @article {pmid38399543, year = {2024}, author = {Karagul, S and Senol, S and Karakose, O and Uzunoglu, K and Kayaalp, C}, title = {One Anastomosis Gastric Bypass versus Roux-en-Y Gastric Bypass: A Randomized Prospective Trial.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {60}, number = {2}, pages = {}, pmid = {38399543}, issn = {1648-9144}, mesh = {Humans ; Adolescent ; Young Adult ; Adult ; Middle Aged ; Aged ; *Gastric Bypass/methods ; Prospective Studies ; *Obesity, Morbid/surgery ; Comorbidity ; Weight Loss ; Retrospective Studies ; }, abstract = {Background and Objectives: One anastomosis gastric bypass (OAGB) and Roux-en-Y gastric bypass (RYGB) surgeries are effective methods used in bariatric surgery. There are limited randomized studies comparing these procedures over more than 2 years. Here, we aimed to compare the 3-year results of two bariatric procedures. Materials and Methods: Patients included in this randomized prospective study were compared in OAGB and RYGB groups. A total of 55 patients, aged between 18 and 65, were eligible for the study. Thirteen patients who did not accept randomization were excluded. Patients were evaluated at 6, 12, 24, and 36 months postoperatively. Results: Three patients were excluded from the study due to loss of communication during the clinical follow-up and one due to death by amyotrophic lateral sclerosis, which started in the eighth month after surgery. The study was completed with a total of 38 patients (OAGB; n = 20, RYGB; n = 18). Patients in the two groups were similar in terms of age, gender, body mass index (BMI), and obesity-related comorbidities. At the end of 3-year follow-up, BMI in the OAGB and RYGB groups was 28.80 ± 4.53 kg/m[2] and 29.17 ± 5.36 kg/m[2], respectively (p = 0.822). Percentage total weight loss (TWL%) was similar. No significant differences were found between the groups regarding percentage excess weight loss (EWL%). Remission of comorbidities was similar. De novo refluxes developed in four OAGB patients; there were no occurrences of these in RYGB patients (p = 0.066). Conclusions: Both OAGB and RYGB are effective in the treatment of morbid obesity. The two procedures are similarly successful in terms of obesity-related comorbidities.}, } @article {pmid38399458, year = {2024}, author = {Al Shaer, D and Al Musaimi, O and Albericio, F and de la Torre, BG}, title = {2023 FDA TIDES (Peptides and Oligonucleotides) Harvest.}, journal = {Pharmaceuticals (Basel, Switzerland)}, volume = {17}, number = {2}, pages = {}, pmid = {38399458}, issn = {1424-8247}, abstract = {A total of nine TIDES (pepTIDES and oligonucleoTIDES) were approved by the FDA during 2023. The four approved oligonucleotides are indicated for various types of disorders, including amyotrophic lateral sclerosis, geographic atrophy, primary hyperoxaluria type 1, and polyneuropathy of hereditary transthyretin-mediated amyloidosis. All oligonucleotides show chemically modified structures to enhance their stability and therapeutic effectiveness as antisense or aptamer oligomers. Some of them demonstrate various types of conjugation to driving ligands. The approved peptides comprise various structures, including linear, cyclic, and lipopeptides, and have diverse applications. Interestingly, the FDA has granted its first orphan drug designation for a peptide-based drug as a highly selective chemokine antagonist. Furthermore, Rett syndrome has found its first-ever core symptoms treatment, which is also peptide-based. Here, we analyze the TIDES approved in 2023 on the basis of their chemical structure, medical target, mode of action, administration route, and common adverse effects.}, } @article {pmid38399373, year = {2024}, author = {Cha, Y and Kagalwala, MN and Ross, J}, title = {Navigating the Frontiers of Machine Learning in Neurodegenerative Disease Therapeutics.}, journal = {Pharmaceuticals (Basel, Switzerland)}, volume = {17}, number = {2}, pages = {}, pmid = {38399373}, issn = {1424-8247}, abstract = {Recent advances in machine learning hold tremendous potential for enhancing the way we develop new medicines. Over the years, machine learning has been adopted in nearly all facets of drug discovery, including patient stratification, lead discovery, biomarker development, and clinical trial design. In this review, we will discuss the latest developments linking machine learning and CNS drug discovery. While machine learning has aided our understanding of chronic diseases like Alzheimer's disease and Parkinson's disease, only modest effective therapies currently exist. We highlight promising new efforts led by academia and emerging biotech companies to leverage machine learning for exploring new therapies. These approaches aim to not only accelerate drug development but to improve the detection and treatment of neurodegenerative diseases.}, } @article {pmid38397958, year = {2024}, author = {Borrego-Hernández, D and Vázquez-Costa, JF and Domínguez-Rubio, R and Expósito-Blázquez, L and Aller, E and Padró-Miquel, A and García-Casanova, P and Colomina, MJ and Martín-Arriscado, C and Osta, R and Cordero-Vázquez, P and Esteban-Pérez, J and Povedano-Panadés, M and García-Redondo, A}, title = {Intermediate Repeat Expansion in the ATXN2 Gene as a Risk Factor in the ALS and FTD Spanish Population.}, journal = {Biomedicines}, volume = {12}, number = {2}, pages = {}, pmid = {38397958}, issn = {2227-9059}, support = {17/00491//Instituto de Salud Carlos III/ ; 21/00286//Instituto de Salud Carlos III/ ; JR19/00030//Instituto de Salud Carlos III/ ; 2021/00737//Instituto de Salud Carlos III/ ; 2017/0653//STOPELA/ ; BOCM142-17/09/2019 pg.105//Spanish Health Ministry/ ; }, abstract = {Intermediate CAG expansions in the gene ataxin-2 (ATXN2) are a known risk factor for ALS, but little is known about their role in FTD risk. Moreover, their contribution to the risk and phenotype of patients might vary in populations with different genetic backgrounds. The aim of this study was to assess the relationship of intermediate CAG expansions in ATXN2 with the risk and phenotype of ALS and FTD in the Spanish population. Repeat-primed PCR was performed in 620 ALS and 137 FTD patients in three referral centers in Spain to determine the exact number of CAG repeats. In our cohort, ≥27 CAG repeats in ATXN2 were associated with a higher risk of developing ALS (odds ratio [OR] = 2.666 [1.471-4.882]; p = 0.0013) but not FTD (odds ratio [OR] = 1.446 [0.558-3.574]; p = 0.44). Moreover, ALS patients with ≥27 CAG repeats in ATXN2 showed a shorter survival rate compared to those with <27 repeats (hazard ratio [HR] 1.74 [1.18, 2.56], p = 0.005), more frequent limb onset (odds ratio [OR] = 2.34 [1.093-4.936]; p = 0.028) and a family history of ALS (odds ratio [OR] = 2.538 [1.375-4.634]; p = 0.002). Intermediate CAG expansions of ≥27 repeats in ATXN2 are associated with ALS risk but not with FTD in the Spanish population. ALS patients carrying an intermediate expansion in ATXN2 show more frequent limb onset but a worse prognosis than those without expansions. In patients carrying C9orf72 expansions, the intermediate ATXN2 expansion might increase the penetrance and modify the phenotype.}, } @article {pmid38397838, year = {2024}, author = {Peggion, C and Calì, T and Brini, M}, title = {Mitochondria Dysfunction and Neuroinflammation in Neurodegeneration: Who Comes First?.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {13}, number = {2}, pages = {}, pmid = {38397838}, issn = {2076-3921}, abstract = {Neurodegenerative diseases (NDs) encompass an assorted array of disorders such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis, each characterised by distinct clinical manifestations and underlying pathological mechanisms. While some cases have a genetic basis, many NDs occur sporadically. Despite their differences, these diseases commonly feature chronic neuroinflammation as a hallmark. Consensus has recently been reached on the possibility that mitochondria dysfunction and protein aggregation can mutually contribute to the activation of neuroinflammatory response and thus to the onset and progression of these disorders. In the present review, we discuss the contribution of mitochondria dysfunction and neuroinflammation to the aetiology and progression of NDs, highlighting the possibility that new potential therapeutic targets can be identified to tackle neurodegenerative processes and alleviate the progression of these pathologies.}, } @article {pmid38396996, year = {2024}, author = {Firdaus, Z and Li, X}, title = {Unraveling the Genetic Landscape of Neurological Disorders: Insights into Pathogenesis, Techniques for Variant Identification, and Therapeutic Approaches.}, journal = {International journal of molecular sciences}, volume = {25}, number = {4}, pages = {}, pmid = {38396996}, issn = {1422-0067}, support = {R01 DK126662/DK/NIDDK NIH HHS/United States ; R01 DK129241/DK/NIDDK NIH HHS/United States ; R01 DK129241 and DK126662/NH/NIH HHS/United States ; }, mesh = {Humans ; *Neurodegenerative Diseases/genetics/therapy/pathology ; *Parkinson Disease/genetics/therapy/pathology ; *Alzheimer Disease/pathology ; *Amyotrophic Lateral Sclerosis/genetics ; }, abstract = {Genetic abnormalities play a crucial role in the development of neurodegenerative disorders (NDDs). Genetic exploration has indeed contributed to unraveling the molecular complexities responsible for the etiology and progression of various NDDs. The intricate nature of rare and common variants in NDDs contributes to a limited understanding of the genetic risk factors associated with them. Advancements in next-generation sequencing have made whole-genome sequencing and whole-exome sequencing possible, allowing the identification of rare variants with substantial effects, and improving the understanding of both Mendelian and complex neurological conditions. The resurgence of gene therapy holds the promise of targeting the etiology of diseases and ensuring a sustained correction. This approach is particularly enticing for neurodegenerative diseases, where traditional pharmacological methods have fallen short. In the context of our exploration of the genetic epidemiology of the three most prevalent NDDs-amyotrophic lateral sclerosis, Alzheimer's disease, and Parkinson's disease, our primary goal is to underscore the progress made in the development of next-generation sequencing. This progress aims to enhance our understanding of the disease mechanisms and explore gene-based therapies for NDDs. Throughout this review, we focus on genetic variations, methodologies for their identification, the associated pathophysiology, and the promising potential of gene therapy. Ultimately, our objective is to provide a comprehensive and forward-looking perspective on the emerging research arena of NDDs.}, } @article {pmid38396946, year = {2024}, author = {Anilkumar, AK and Vij, P and Lopez, S and Leslie, SM and Doxtater, K and Khan, MM and Yallapu, MM and Chauhan, SC and Maestre, GE and Tripathi, MK}, title = {Long Non-Coding RNAs: New Insights in Neurodegenerative Diseases.}, journal = {International journal of molecular sciences}, volume = {25}, number = {4}, pages = {}, pmid = {38396946}, issn = {1422-0067}, support = {DP1 AG069870/AG/NIA NIH HHS/United States ; P30 AG066546/AG/NIA NIH HHS/United States ; R16 GM146696/GM/NIGMS NIH HHS/United States ; }, mesh = {Humans ; *Neurodegenerative Diseases/genetics/pathology ; *RNA, Long Noncoding/genetics ; *Alzheimer Disease ; *Parkinson Disease/genetics ; *Amyotrophic Lateral Sclerosis/genetics ; }, abstract = {Neurodegenerative diseases (NDDs), including Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS), are gradually becoming a burden to society. The adverse effects and mortality/morbidity rates associated with these NDDs are a cause of many healthcare concerns. The pathologic alterations of NDDs are related to mitochondrial dysfunction, oxidative stress, and inflammation, which further stimulate the progression of NDDs. Recently, long non-coding RNAs (lncRNAs) have attracted ample attention as critical mediators in the pathology of NDDs. However, there is a significant gap in understanding the biological function, molecular mechanisms, and potential importance of lncRNAs in NDDs. This review documents the current research on lncRNAs and their implications in NDDs. We further summarize the potential implication of lncRNAs to serve as novel therapeutic targets and biomarkers for patients with NDDs.}, } @article {pmid38396337, year = {2024}, author = {Genge, A and Cedarbaum, JM and Shefner, J and Chio, A and Al-Chalabi, A and Van Damme, P and McDermott, C and Glass, J and Berry, J and van Eijk, RPA and Fournier, C and Grosskreutz, J and Andrews, J and Bertone, V and Bunte, TM and Couillard, M and Cummings, C and Kittle, G and Polzer, J and Salmon, K and Straub, C and van den Berg, LH}, title = {The ALSFRS-R Summit: a global call to action on the use of the ALSFRS-R in ALS clinical trials.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {25}, number = {3-4}, pages = {382-387}, doi = {10.1080/21678421.2024.2320880}, pmid = {38396337}, issn = {2167-9223}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/drug therapy ; Severity of Illness Index ; Disease Progression ; }, abstract = {The Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS) was developed more than 25 years ago as an instrument to monitor functional change over time in patients with ALS. It has since been revised and extended to meet the needs of high data quality in ALS trials (ALSFRS-R), however a full re-validation of the scale was not completed. Despite this, the scale has remained a primary outcome measure in clinical trials. We convened a group of clinical trialists to discuss and explore opportunities to improve the scale and propose alternative measures. In this meeting report, we present a call to action on the use of the ALSFRS-Revised scale in clinical trials, focusing on the need for (1) harmonization of the ALSFRS-R administration globally, (2) alignment on a set of recommendations for clinical trial design and statistical analysis plans (SAPs), and (3) use of additional outcome measures.}, } @article {pmid38395965, year = {2024}, author = {Markovinovic, A and Martín-Guerrero, SM and Mórotz, GM and Salam, S and Gomez-Suaga, P and Paillusson, S and Greig, J and Lee, Y and Mitchell, JC and Noble, W and Miller, CCJ}, title = {Stimulating VAPB-PTPIP51 ER-mitochondria tethering corrects FTD/ALS mutant TDP43 linked Ca[2+] and synaptic defects.}, journal = {Acta neuropathologica communications}, volume = {12}, number = {1}, pages = {32}, pmid = {38395965}, issn = {2051-5960}, support = {MR/R022666/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/pathology ; Calcium/metabolism ; Endoplasmic Reticulum/metabolism ; *Frontotemporal Dementia/genetics/metabolism ; Glycogen Synthase Kinase 3 beta/metabolism ; Mitochondria/metabolism ; *Neurodegenerative Diseases/metabolism ; Protein Tyrosine Phosphatases/metabolism ; Synapses/pathology ; TDP-43 Proteinopathies/metabolism ; *Vesicular Transport Proteins/genetics ; }, abstract = {Frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) are clinically linked major neurodegenerative diseases. Notably, TAR DNA-binding protein-43 (TDP43) accumulations are hallmark pathologies of FTD/ALS and mutations in the gene encoding TDP43 cause familial FTD/ALS. There are no cures for FTD/ALS. FTD/ALS display damage to a broad range of physiological functions, many of which are regulated by signaling between the endoplasmic reticulum (ER) and mitochondria. This signaling is mediated by the VAPB-PTPIP51 tethering proteins that serve to recruit regions of ER to the mitochondrial surface so as to facilitate inter-organelle communications. Several studies have now shown that disrupted ER-mitochondria signaling including breaking of the VAPB-PTPIP51 tethers are features of FTD/ALS and that for TDP43 and other familial genetic FTD/ALS insults, this involves activation of glycogen kinase-3β (GSK3β). Such findings have prompted suggestions that correcting damage to ER-mitochondria signaling and the VAPB-PTPIP51 interaction may be broadly therapeutic. Here we provide evidence to support this notion. We show that overexpression of VAPB or PTPIP51 to enhance ER-mitochondria signaling corrects mutant TDP43 induced damage to inositol 1,4,5-trisphosphate (IP3) receptor delivery of Ca[2+] to mitochondria which is a primary function of the VAPB-PTPIP51 tethers, and to synaptic function. Moreover, we show that ursodeoxycholic acid (UDCA), an FDA approved drug linked to FTD/ALS and other neurodegenerative diseases therapy and whose precise therapeutic target is unclear, corrects TDP43 linked damage to the VAPB-PTPIP51 interaction. We also show that this effect involves inhibition of TDP43 mediated activation of GSK3β. Thus, correcting damage to the VAPB-PTPIP51 tethers may have therapeutic value for FTD/ALS and other age-related neurodegenerative diseases.}, } @article {pmid38395927, year = {2024}, author = {Baranova, A and Zhao, Q and Cao, H and Chandhoke, V and Zhang, F}, title = {Causal influences of neuropsychiatric disorders on Alzheimer's disease.}, journal = {Translational psychiatry}, volume = {14}, number = {1}, pages = {114}, pmid = {38395927}, issn = {2158-3188}, mesh = {Humans ; *Alzheimer Disease/genetics ; *Schizophrenia/epidemiology/genetics ; *Parkinson Disease/genetics ; *Attention Deficit Disorder with Hyperactivity/genetics ; *Migraine Disorders/genetics ; Genome-Wide Association Study ; }, abstract = {Previous studies have observed a significant comorbidity between Alzheimer's disease (AD) and some other neuropsychiatric disorders. However, the mechanistic connections between neuropsychiatric disorders and AD are not well understood. We conducted a Mendelian randomization analysis to appraise the potential influences of 18 neurodegenerative and neuropsychiatric disorders on AD. We found that four disorders are causally associated with increased risk for AD, including bipolar disorder (BD) (OR: 1.09), migraine (OR: 1.09), schizophrenia (OR: 1.05), and Parkinson's disease (PD) (OR: 1.07), while attention-deficit/hyperactivity disorder (ADHD) was associated with a decreased risk for AD (OR: 0.80). In case of amyotrophic lateral sclerosis (OR: 1.04) and Tourette's syndrome (OR: 1.05), there was suggestive evidence of their causal effects of on AD. Our study shows that genetic components predisposing to BD, migraine, schizophrenia, and PD may promote the development of AD, while ADHD may be associated with a reduced risk of AD. The treatments aimed at alleviating neuropsychiatric diseases with earlier onset may also influence the risk of AD-related cognitive decline, which is typically observed later in life.}, } @article {pmid38394955, year = {2024}, author = {Lim, JX and Fong, E and Goh, C and Ng, LP and Low, DCY and Seow, WT and Low, SYY}, title = {Complex lumbosacral spinal cord lipomas: A longitudinal study on outcomes from a Singapore children's hospital.}, journal = {Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia}, volume = {121}, number = {}, pages = {119-128}, doi = {10.1016/j.jocn.2024.02.017}, pmid = {38394955}, issn = {1532-2653}, mesh = {Child ; Humans ; Infant ; Longitudinal Studies ; Retrospective Studies ; Treatment Outcome ; Singapore/epidemiology ; *Spinal Cord Neoplasms/diagnostic imaging/surgery ; Spinal Cord ; *Lipoma/surgery ; Hospitals ; Lumbosacral Region/surgery ; }, abstract = {BACKGROUND: Total/near-total resection (TR/NTR) of complex lumbosacral lipomas (CSL) is reported to be associated with better long-term functional outcomes and lower symptomatic re-tethering rates. We report our institutional experience for CSL resection in affected children.

METHODS: This is a single-institution, retrospective study. Inclusion criteria consist of patients with CSL with dorsal, transitional and chaotic lipomas based on Pang et al's classification. The study population is divided into 2 groups: asymptomatic patients with a normal preoperative workup referred to as 'prophylactic intent' and 'therapeutic intent' for those with pre-existing neuro-urological symptoms. Primary aims are to review factors that affect post-operative clean intermittent catheterization (CIC), functional outcomes based on Necker functional score (NFS), and re-tethering rates.

RESULTS: 122 patients were included from 2000 to 2021. There were 32 dorsal lipomas (26.2 %), 74 transitional lipomas (60.7 %), and 16 chaotic lipomas (13.1 %). 82 % patients achieved TR/NTR. Favourable NFS at 1-year was 48.2 %. The re-tethering rate was 6.6 %. After multivariable analysis, post-operative CIC was associated with median age at surgery (p = 0.026), lipoma type (p = 0.029), conus height (p = 0.048) and prophylactic intent (p < 0.001). Next, extent of lipoma resection (p = 0.012) and the post-operative CSF leak (p = 0.004) were associated with re-tethering. Favourable NFS was associated with lipoma type (p = 0.047) and prophylactic intent surgery (p < 0.001).

CONCLUSIONS: Our experience shows that TR/NTR for CSL is a feasible option to prevent functional deterioration and re-tethering. Efforts are needed to work on factors associated with post-operative CIC.}, } @article {pmid38394210, year = {2024}, author = {Chang, YJ and Lin, KT and Shih, O and Yang, CH and Chuang, CY and Fang, MH and Lai, WB and Lee, YC and Kuo, HC and Hung, SC and Yao, CK and Jeng, US and Chen, YR}, title = {Sulfated disaccharide protects membrane and DNA damages from arginine-rich dipeptide repeats in ALS.}, journal = {Science advances}, volume = {10}, number = {8}, pages = {eadj0347}, pmid = {38394210}, issn = {2375-2548}, mesh = {Animals ; Mice ; Humans ; *Amyotrophic Lateral Sclerosis/drug therapy/genetics ; Dipeptides/pharmacology ; Arginine/genetics ; Sulfates ; Drosophila/genetics ; DNA Damage ; DNA Repeat Expansion ; C9orf72 Protein/genetics/metabolism ; }, abstract = {Hexanucleotide repeat expansion in C9ORF72 (C9) is the most prevalent mutation among amyotrophic lateral sclerosis (ALS) patients. The patients carry over ~30 to hundreds or thousands of repeats translated to dipeptide repeats (DPRs) where poly-glycine-arginine (GR) and poly-proline-arginine (PR) are most toxic. The structure-function relationship is still unknown. Here, we examined the minimal neurotoxic repeat number of poly-GR and found that extension of the repeat number led to a loose helical structure disrupting plasma and nuclear membrane. Poly-GR/PR bound to nucleotides and interfered with transcription. We screened and identified a sulfated disaccharide that bound to poly-GR/PR and rescued poly-GR/PR-induced toxicity in neuroblastoma and C9-ALS-iPSC-derived motor neurons. The compound rescued the shortened life span and defective locomotion in poly-GR/PR expressing Drosophila model and improved motor behavior in poly-GR-injected mouse model. Overall, our results reveal structural and toxicity mechanisms for poly-GR/PR and facilitate therapeutic development for C9-ALS.}, } @article {pmid38393638, year = {2024}, author = {Gowda, VK and Babu, S and Kinhal, U and Srinivasan, VM}, title = {Amyotrophic Lateral Sclerosis due to ALS2 Pathogenic Variant Masquerading as Cerebral Palsy.}, journal = {Indian journal of pediatrics}, volume = {91}, number = {8}, pages = {872}, pmid = {38393638}, issn = {0973-7693}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/genetics ; *Cerebral Palsy/diagnosis ; Diagnosis, Differential ; Male ; Guanine Nucleotide Exchange Factors/genetics ; }, } @article {pmid38393299, year = {2024}, author = {García-Parra, B and Guiu, JM and Povedano, M and Mariño, EL and Modamio, P}, title = {Geographical distribution of clinical trials in amyotrophic lateral sclerosis: a scoping review.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {25}, number = {3-4}, pages = {376-381}, doi = {10.1080/21678421.2024.2320881}, pmid = {38393299}, issn = {2167-9223}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/epidemiology/genetics/therapy ; Belgium ; France ; Germany ; United Kingdom ; }, abstract = {Introduction: Clinical trials location is determined by many factors, including the availability of patient populations, regulatory environment, scientific expertise, and cost considerations. In clinical drug development of amyotrophic lateral sclerosis (ALS), where genetic differences have been described and may be related to geographic setting, this could have implications for the clinical interpretation of results in underrepresented geographic settings. Objective: The aim of this study was to review country participation in ALS clinical research based on available data from clinical trial registries and databases. Methods: We performed a scoping review with available information about clinical trials on ALS in ClinicalTrials.gov (CT), EU clinical trials register (EudraCT), WHO International Clinical Trials Registry Platform (ICTRP) and Web of Science (WOS). Inclusion criteria were clinical trials in phase 2 and 3 to treat ALS, recruiting or active not recruiting, from 23/06/2018 to 23/06/2023. Results: The total number of clinical trials identified were 188; 54 studies in CT, 38 in EudraCT, 47 in ICTRP and 49 in WOS. We identified 77 clinical trials after deleting duplicates and applying exclusion criteria. The countries with most studies conducted were the US with 35 studies (10.9%), followed by the United Kingdom, Belgium, France and Germany with 21 studies each one of them (6.5%). Conclusion: The data obtained in our review showed a non-homogeneous distribution in clinical trials at the international level, which may influence the interpretation of the results obtained.}, } @article {pmid38392311, year = {2024}, author = {Dratch, L and Bardakjian, TM and Johnson, K and Babaian, N and Gonzalez-Alegre, P and Elman, L and Quinn, C and Guo, MH and Scherer, SS and Amado, DA}, title = {The Importance of Offering Exome or Genome Sequencing in Adult Neuromuscular Clinics.}, journal = {Biology}, volume = {13}, number = {2}, pages = {}, pmid = {38392311}, issn = {2079-7737}, support = {K08 NS114106/NS/NINDS NIH HHS/United States ; }, abstract = {Advances in gene-specific therapeutics for patients with neuromuscular disorders (NMDs) have brought increased attention to the importance of genetic diagnosis. Genetic testing practices vary among adult neuromuscular clinics, with multi-gene panel testing currently being the most common approach; follow-up testing using broad-based methods, such as exome or genome sequencing, is less consistently offered. Here, we use five case examples to illustrate the unique ability of broad-based testing to improve diagnostic yield, resulting in identification of SORD-neuropathy, HADHB-related disease, ATXN2-ALS, MECP2 related progressive gait decline and spasticity, and DNMT1-related cerebellar ataxia, deafness, narcolepsy, and hereditary sensory neuropathy type 1E. We describe in each case the technological advantages that enabled identification of the causal gene, and the resultant clinical and personal implications for the patient, demonstrating the importance of offering exome or genome sequencing to adults with NMDs.}, } @article {pmid38392286, year = {2024}, author = {Jackson, WS and Bauer, S and Kaczmarczyk, L and Magadi, SS}, title = {Selective Vulnerability to Neurodegenerative Disease: Insights from Cell Type-Specific Translatome Studies.}, journal = {Biology}, volume = {13}, number = {2}, pages = {}, pmid = {38392286}, issn = {2079-7737}, support = {grant # 990868//the Konung Gustaf V:s och Drottning Victorias Stiftelse; the Wallenberg Center for Molecular Medicine;the Hereditary Disease Foundation/ ; }, abstract = {Neurodegenerative diseases (NDs) manifest a wide variety of clinical symptoms depending on the affected brain regions. Gaining insights into why certain regions are resistant while others are susceptible is vital for advancing therapeutic strategies. While gene expression changes offer clues about disease responses across brain regions, the mixture of cell types therein obscures experimental results. In recent years, methods that analyze the transcriptomes of individual cells (e.g., single-cell RNA sequencing or scRNAseq) have been widely used and have provided invaluable insights into specific cell types. Concurrently, transgene-based techniques that dissect cell type-specific translatomes (CSTs) in model systems, like RiboTag and bacTRAP, offer unique advantages but have received less attention. This review juxtaposes the merits and drawbacks of both methodologies, focusing on the use of CSTs in understanding conditions like amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), Alzheimer's disease (AD), and specific prion diseases like fatal familial insomnia (FFI), genetic Creutzfeldt-Jakob disease (gCJD), and acquired prion disease. We conclude by discussing the emerging trends observed across multiple diseases and emerging methods.}, } @article {pmid38392208, year = {2024}, author = {Fukatsu, S and Okawa, M and Okabe, M and Cho, M and Isogai, M and Yokoi, T and Shirai, R and Oizumi, H and Yamamoto, M and Ohbuchi, K and Miyamoto, Y and Yamauchi, J}, title = {Modulating Golgi Stress Signaling Ameliorates Cell Morphological Phenotypes Induced by CHMP2B with Frontotemporal Dementia-Associated p.Asp148Tyr.}, journal = {Current issues in molecular biology}, volume = {46}, number = {2}, pages = {1398-1412}, pmid = {38392208}, issn = {1467-3045}, abstract = {Some charged multivesicular body protein 2B (CHMP2B) mutations are associated with autosomal-dominant neurodegenerative frontotemporal dementia and/or amyotrophic lateral sclerosis type 7 (FTDALS7). The main aim of this study is to clarify the relationship between the expression of mutated CHMP2B protein displaying FTD symptoms and defective neuronal differentiation. First, we illustrate that the expression of CHMP2B with the Asp148Tyr (D148Y) mutation, which preferentially displays FTD phenotypes, blunts neurite process elongation in rat primary cortical neurons. Similar results were observed in the N1E-115 cell line, a model that undergoes neurite elongation. Second, these effects were also accompanied by changes in neuronal differentiation marker protein expression. Third, wild-type CHMP2B protein was indeed localized in the endosomal sorting complexes required to transport (ESCRT)-like structures throughout the cytoplasm. In contrast, CHMP2B with the D148Y mutation exhibited aggregation-like structures and accumulated in the Golgi body. Fourth, among currently known Golgi stress regulators, the expression levels of Hsp47, which has protective effects on the Golgi body, were decreased in cells expressing CHMP2B with the D148Y mutation. Fifth, Arf4, another Golgi stress-signaling molecule, was increased in mutant-expressing cells. Finally, when transfecting Hsp47 or knocking down Arf4 with small interfering (si)RNA, cellular phenotypes in mutant-expressing cells were recovered. These results suggest that CHMP2B with the D148Y mutation, acting through Golgi stress signaling, is negatively involved in the regulation of neuronal cell morphological differentiation, providing evidence that a molecule controlling Golgi stress may be one of the potential FTD therapeutic targets at the molecular and cellular levels.}, } @article {pmid38391754, year = {2024}, author = {Leão Batista Simões, J and Webler Eichler, S and Raitz Siqueira, ML and de Carvalho Braga, G and Bagatini, MD}, title = {Amyotrophic Lateral Sclerosis in Long-COVID Scenario and the Therapeutic Potential of the Purinergic System in Neuromodulation.}, journal = {Brain sciences}, volume = {14}, number = {2}, pages = {}, pmid = {38391754}, issn = {2076-3425}, support = {Proj. No 404256/2021-0 and 310606/2021-7).//National Council for Scientific and Technological Development/ ; }, abstract = {Amyotrophic lateral sclerosis (ALS) involves the degeneration of motor neurons and debilitating and possibly fatal symptoms. The COVID-19 pandemic directly affected the quality of life of this group, and the SARS-CoV-2 infection accelerated the present neuroinflammatory process. Furthermore, studies indicate that the infection may have led to the development of the pathology. Thus, the scenario after this pandemic presents "long-lasting COVID" as a disease that affects people who have been infected. From this perspective, studying the pathophysiology behind ALS associated with SARS-CoV-2 infection and possible supporting therapies becomes necessary when we understand the impact on the quality of life of these patients. Thus, the purinergic system was trained to demonstrate how its modulation can add to the treatment, reduce disease progression, and result in better prognoses. From our studies, we highlight the P2X7, P2X4, and A2AR receptors and how their activity can directly influence the ALS pathway.}, } @article {pmid38391732, year = {2024}, author = {Yang, K and Liu, Y and Zhang, M}, title = {The Diverse Roles of Reactive Astrocytes in the Pathogenesis of Amyotrophic Lateral Sclerosis.}, journal = {Brain sciences}, volume = {14}, number = {2}, pages = {}, pmid = {38391732}, issn = {2076-3425}, support = {82271478//National Natural Science Foundation of China/ ; }, abstract = {Astrocytes displaying reactive phenotypes are characterized by their ability to remodel morphologically, molecularly, and functionally in response to pathological stimuli. This process results in the loss of their typical astrocyte functions and the acquisition of neurotoxic or neuroprotective roles. A growing body of research indicates that these reactive astrocytes play a pivotal role in the pathogenesis of amyotrophic lateral sclerosis (ALS), involving calcium homeostasis imbalance, mitochondrial dysfunction, abnormal lipid and lactate metabolism, glutamate excitotoxicity, etc. This review summarizes the characteristics of reactive astrocytes, their role in the pathogenesis of ALS, and recent advancements in astrocyte-targeting strategies.}, } @article {pmid38391731, year = {2024}, author = {Manera, U and Torrieri, MC and Moglia, C and Canosa, A and Vasta, R and Palumbo, F and Matteoni, E and Cabras, S and Grassano, M and Bombaci, A and Mattei, A and Bellocchia, M and Tabbia, G and Ribolla, F and Chiò, A and Calvo, A}, title = {Calculated Maximal Volume Ventilation (cMVV) as a Marker of Early Respiratory Failure in Amyotrophic Lateral Sclerosis (ALS).}, journal = {Brain sciences}, volume = {14}, number = {2}, pages = {}, pmid = {38391731}, issn = {2076-3425}, support = {GA101017598//European Union's Horizon 2020/ ; RF-2016-02362405//the Italian Ministry of Health/ ; 2017SNW5MB//Italian Ministry of Education, University and Research/ ; 259867//European Commission's Health Seventh Framework Programme/ ; Strength, ALS-Care and Brain-Mend projects//Joint Programme-Neurodegenerative Disease Research/ ; Department of Excellence grant//Italian Ministry of University and Research/ ; }, abstract = {Respiratory failure assessment is among the most debatable research topics in amyotrophic lateral sclerosis (ALS) clinical research due to the wide heterogeneity of its presentation. Among the different pulmonary function tests (PFTs), maximal voluntary ventilation (MVV) has shown potential utility as a diagnostic and monitoring marker, able to capture early respiratory modification in neuromuscular disorders. In the present study, we explored calculated MVV (cMVV) as a prognostic biomarker in a center-based, retrospective ALS population belonging to the Piemonte and Valle d'Aosta registry for ALS (PARALS). A Spearman's correlation analysis with clinical data and PFTs showed a good correlation of cMVV with forced vital capacity (FVC) and a moderate correlation with some other features such as bulbar involvement, ALSFRS-R total score, blood oxygen (pO2), carbonate (HCO3[-]), and base excess (BE), measured with arterial blood gas analysis. Both the Cox proportional hazard models for survival and the time to non-invasive ventilation (NIV) measurement highlighted that cMVV at diagnosis (considering cMVV(40) ≥ 80) is able to stratify patients across different risk levels for death/tracheostomy and NIV indication, especially considering patients with FVC% ≥ 80. In conclusion, cMVV is a useful marker of early respiratory failure in ALS, and is easily derivable from standard PFTs, especially in asymptomatic ALS patients with normal FVC measures.}, } @article {pmid38390994, year = {2024}, author = {Nájera-Maldonado, JM and Salazar, R and Alvarez-Fitz, P and Acevedo-Quiroz, M and Flores-Alfaro, E and Hernández-Sotelo, D and Espinoza-Rojo, M and Ramírez, M}, title = {Phenolic Compounds of Therapeutic Interest in Neuroprotection.}, journal = {Journal of xenobiotics}, volume = {14}, number = {1}, pages = {227-246}, pmid = {38390994}, issn = {2039-4713}, support = {A1-S-34290 to Monica Ramirez//Consejo Nacional de Humanidades, Ciencias y Tecnologías/ ; }, abstract = {The number of elderly people is projected to double in the next 50 years worldwide, resulting in an increased prevalence of neurodegenerative diseases. Aging causes changes in brain tissue homeostasis, thus contributing to the development of neurodegenerative disorders. Current treatments are not entirely effective, so alternative treatments or adjuvant agents are being actively sought. Antioxidant properties of phenolic compounds are of particular interest for neurodegenerative diseases whose psychopathological mechanisms strongly rely on oxidative stress at the brain level. Moreover, phenolic compounds display other advantages such as the permeability of the blood-brain barrier (BBB) and the interesting molecular mechanisms that we reviewed in this work. We began by briefly outlining the physiopathology of neurodegenerative diseases to understand the mechanisms that result in irreversible brain damage, then we provided an overall classification of the phenolic compounds that would be addressed later. We reviewed in vitro and in vivo studies, as well as some clinical trials in which neuroprotective mechanisms were demonstrated in models of different neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), Parkinson's disease (PD), ischemia, and traumatic brain injury (TBI).}, } @article {pmid38390945, year = {2024}, author = {Fukatsu, S and Sashi, H and Shirai, R and Takagi, N and Oizumi, H and Yamamoto, M and Ohbuchi, K and Miyamoto, Y and Yamauchi, J}, title = {Rab11a Controls Cell Shape via C9orf72 Protein: Possible Relationships to Frontotemporal Dementia/Amyotrophic Lateral Sclerosis (FTDALS) Type 1.}, journal = {Pathophysiology : the official journal of the International Society for Pathophysiology}, volume = {31}, number = {1}, pages = {100-116}, pmid = {38390945}, issn = {1873-149X}, abstract = {Abnormal nucleotide insertions of C9orf72, which forms a complex with Smith-Magenis syndrome chromosomal region candidate gene 8 (SMCR8) protein and WD repeat-containing protein 41 (WDR41) protein, are associated with an autosomal-dominant neurodegenerative frontotemporal dementia and/or amyotrophic lateral sclerosis type 1 (FTDALS1). The differentially expressed in normal and neoplastic cells (DENN) domain-containing C9orf72 and its complex with SMCR8 and WDR41 function as a guanine-nucleotide exchange factor for Rab GTP/GDP-binding proteins (Rab GEF, also called Rab activator). Among Rab proteins serving as major effectors, there exists Rab11a. However, it remains to be established which Rab protein is related to promoting or sustaining neuronal morphogenesis or homeostasis. In this study, we describe that the knockdown of Rab11a decreases the expression levels of neuronal differentiation marker proteins, as well as the elongation of neurite-like processes, using N1E-115 cells, a well-utilized neuronal differentiation model. Similar results were obtained in primary cortical neurons. In contrast, the knockdown of Rab11b, a Rab11a homolog, did not significantly affect their cell morphological changes. It is of note that treatment with hesperetin, a citrus flavonoid (also known as Vitamin P), recovered the neuronal morphological phenotypes induced by Rab11a knockdown. Also, the knockdown of Rab11a or Rab11b led to a decrease in glial marker expression levels and in morphological changes in FBD-102b cells, which serve as the oligodendroglial differentiation model. Rab11a is specifically involved in the regulation of neuronal morphological differentiation. The knockdown effect mimicking the loss of function of C9orf72 is reversed by treatment with hesperetin. These findings may reveal a clue for identifying one of the potential molecular and cellular phenotypes underlying FTDALS1.}, } @article {pmid38389786, year = {2024}, author = {Berthiaume, AA and Reda, SM and Kleist, KN and Setti, SE and Wu, W and Johnston, JL and Taylor, RW and Stein, LR and Moebius, HJ and Church, KJ}, title = {ATH-1105, a small-molecule positive modulator of the neurotrophic HGF system, is neuroprotective, preserves neuromotor function, and extends survival in preclinical models of ALS.}, journal = {Frontiers in neuroscience}, volume = {18}, number = {}, pages = {1348157}, pmid = {38389786}, issn = {1662-4548}, abstract = {INTRODUCTION: Amyotrophic lateral sclerosis (ALS), a progressive and fatal neurodegenerative disorder, primarily affects the motor neurons of the brain and spinal cord. Like other neurodegenerative conditions, ongoing pathological processes such as increased inflammation, excitotoxicity, and protein accumulation contribute to neuronal death. Hepatocyte growth factor (HGF) signaling through the MET receptor promotes pro-survival, anti-apoptotic, and anti-inflammatory effects in multiple cell types, including the neurons and support cells of the nervous system. This pleiotropic system is therefore a potential therapeutic target for treatment of neurodegenerative disorders such as ALS. Here, we test the effects of ATH-1105, a small-molecule positive modulator of the HGF signaling system, in preclinical models of ALS.

METHODS: In vitro, the impact of ATH-1105 on HGF-mediated signaling was assessed via phosphorylation assays for MET, extracellular signal-regulated kinase (ERK), and protein kinase B (AKT). Neuroprotective effects of ATH-1105 were evaluated in rat primary neuron models including spinal motor neurons, motor neuron-astrocyte cocultures, and motor neuron-human muscle cocultures. The anti-inflammatory effects of ATH-1105 were evaluated in microglia- and macrophage-like cell systems exposed to lipopolysaccharide (LPS). In vivo, the impact of daily oral treatment with ATH-1105 was evaluated in Prp-TDP43[A315T] hemizygous transgenic ALS mice.

RESULTS: In vitro, ATH-1105 augmented phosphorylation of MET, ERK, and AKT. ATH-1105 attenuated glutamate-mediated excitotoxicity in primary motor neurons and motor neuron- astrocyte cocultures, and had protective effects on motor neurons and neuromuscular junctions in motor neuron-muscle cocultures. ATH-1105 mitigated LPS-induced inflammation in microglia- and macrophage-like cell systems. In vivo, ATH-1105 treatment resulted in improved motor and nerve function, sciatic nerve axon and myelin integrity, and survival in ALS mice. Treatment with ATH-1105 also led to reductions in levels of plasma biomarkers of inflammation and neurodegeneration, along with decreased pathological protein accumulation (phospho-TDP-43) in the sciatic nerve. Additionally, both early intervention (treatment initiation at 1 month of age) and delayed intervention (treatment initiation at 2 months of age) with ATH-1105 produced benefits in this preclinical model of ALS.

DISCUSSION: The consistent neuroprotective and anti-inflammatory effects demonstrated by ATH-1105 preclinically provide a compelling rationale for therapeutic interventions that leverage the positive modulation of the HGF pathway as a treatment for ALS.}, } @article {pmid38389507, year = {2024}, author = {Al Ojaimi, Y and Slek, C and Osman, S and Alarcan, H and Marouillat, S and Corcia, P and Vourc'h, P and Lanznaster, D and Blasco, H}, title = {The effect of pH alterations on TDP-43 in a cellular model of amyotrophic lateral sclerosis.}, journal = {Biochemistry and biophysics reports}, volume = {38}, number = {}, pages = {101664}, pmid = {38389507}, issn = {2405-5808}, abstract = {Amyotrophic Lateral Sclerosis (ALS) is the most common neurodegenerative disease affecting motor neurons. The pathophysiology of ALS is not well understood but TDP-43 proteinopathy (aggregation and mislocalization) is one of the major phenomena described. Several factors can influence TDP-43 behavior such as mild pH alterations that can induce conformational changes in recombinant TDP-43, increasing its propensity to aggregate. However to our knowledge, no studies have been conducted yet in a cellular setting, in the context of ALS. We therefore tested the effect of cellular pH alterations on the localization, aggregation, and phosphorylation of TDP-43. HEK293T cells overexpressing wildtype TDP-43 were incubated for 1 h with solutions of different pH (6.4, 7.2, and 8). Incubation of cells for 1 h in solutions of pH 6.4 and 8 led to an increase in TDP-43-positive puncta. This was accompanied by the mislocalization of TDP-43 from the nucleus to the cytoplasm. Our results suggest that small alterations in cellular pH affect TDP-43 and increase its mislocalization into cytoplasmic TDP-43-positive puncta, which might suggest a role of TDP-43 in the response of cells to pH alterations.}, } @article {pmid38389222, year = {2024}, author = {Consonni, M and Faltracco, V and Dalla Bella, E and Telesca, A and Bersano, E and Nigri, A and Demichelis, G and Medina, JP and Bruzzone, MG and Lauria, G}, title = {Loneliness as neurobehavioral issue in amyotrophic lateral sclerosis.}, journal = {Annals of clinical and translational neurology}, volume = {11}, number = {5}, pages = {1122-1134}, pmid = {38389222}, issn = {2328-9503}, support = {2015-0023//Fondazione Regionale per la Ricerca Biomedica, Regione Lombardia/ ; 1157625//Fondo Europeo di Sviluppo Regionale, Regione Lombardia/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology/psychology/diagnostic imaging ; Male ; *Loneliness/psychology ; Female ; Aged ; Middle Aged ; *Quality of Life ; Magnetic Resonance Imaging ; Cognitive Dysfunction/etiology/physiopathology/diagnostic imaging ; Depression/physiopathology ; }, abstract = {OBJECTIVE: In elderly people loneliness represents a risk factor for dementia and may negatively impact on mental and physical health. The specific contribute of loneliness to cognitive and behavioral functioning have not yet been determined in amyotrophic lateral sclerosis (ALS). Our hypothesis was that loneliness may be related to motor dysfunction with a negative impact on cognitive and behavioral decline, possibly related to specific cortical involvement.

METHODS: In 200 ALS patients (ALSpts) and 50 healthy controls (HCs) we measured loneliness, mood, and quality of life (QoL). ALSpts underwent comprehensive clinical, genetic, and neuropsychological assessment to define phenotypes. Seventy-seven ALSpts performed 3T MRI scans to measure cortical thickness. Between-group, partial correlation and regression analyses were used to examined clinical, neuropsychological, and cortical signatures of loneliness.

RESULTS: Feelings of loneliness were documented in 38% of ALSpts (ALS/L+pts) and in 47% of HCs. In both groups loneliness was associated with anxiety (P < 0.001), depression (P ≤ 0.005), and poor QoL (P < 0.001). ALS/L+pts had similar motor dysfunctions and cognitive abilities than non-lonely ALSpts, but distinct behavioral profiles (P ≤ 0.005) and frontoparietal involvement (P < 0.05). Loneliness in ALS is related to behavioral changes, apathy, and emotional dysregulation (P < 0.001).

INTERPRETATION: Our cross-sectional study indicates that, in ALS, the satisfaction of social environment is associated with a sense of life well-being that is not limited to the motor status, proving instead that loneliness can impact on disease-related neurobehavioral changes with a possible flashback on brain architecture. This suggests that sociality could promote personal resilience against behavioral and affective decline in ALS.}, } @article {pmid38389123, year = {2024}, author = {Sainouchi, M and Oginezawa, S and Tada, M and Ishihara, T and Onodera, O and Kakita, A}, title = {Slow disease progression and characteristic TDP-43 inclusions in a patient with familial amyotrophic lateral sclerosis carrying a TARDBP G357S variant.}, journal = {Neuropathology and applied neurobiology}, volume = {50}, number = {1}, pages = {e12966}, doi = {10.1111/nan.12966}, pmid = {38389123}, issn = {1365-2990}, support = {22H02995//JSPS/ ; 23H00434//JSPS/ ; 21K07272//JSPS/ ; JP23jm0210097//AMED-SICORP/ ; //Grants-in Aid from the Research Committee of CNS Degenerative Diseases/ ; //Research on Policy Planning and Evaluation for Rare and Intractable Diseases/ ; //Health, Labour and Welfare Sciences Research Grants/ ; //Ministry of Health, Labour and Welfare, Japan/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics ; Disease Progression ; DNA-Binding Proteins/genetics ; Mutation ; }, } @article {pmid38388775, year = {2024}, author = {Pang, D and Yu, Y and Zhao, B and Huang, J and Cui, Y and Li, T and Li, C and Shang, H}, title = {The Long Non-Coding RNA NR3C2-8:1 Promotes p53-Mediated Apoptosis through the miR-129-5p/USP10 Axis in Amyotrophic Lateral Sclerosis.}, journal = {Molecular neurobiology}, volume = {61}, number = {10}, pages = {7466-7480}, pmid = {38388775}, issn = {1559-1182}, support = {81871000//National Natural Science Foundation of China/ ; 2022NSFSC0750//Sichuan Province Science and Technology Support Program/ ; }, mesh = {*RNA, Long Noncoding/genetics/metabolism ; *Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology ; Humans ; *Tumor Suppressor Protein p53/metabolism/genetics ; *Apoptosis/genetics ; *MicroRNAs/genetics/metabolism ; *Ubiquitin Thiolesterase/genetics/metabolism ; Male ; Signal Transduction/genetics ; Up-Regulation/genetics ; Base Sequence ; }, abstract = {Motor neuron degeneration in amyotrophic lateral sclerosis (ALS) is a form of apoptosis, but the mechanisms underlying this neuronal cell death remain unclear. Numerous studies demonstrate abnormally elevated and active p53 in the central nervous system of ALS patients. Activation of p53-regulated pro-apoptotic signaling pathways may trigger motor neuron death. We previously reported decreased expression of the long non-coding RNA NR3C2-8:1 (Lnc-NR3C) in leukocytes of ALS patients. Here, we show lnc-NR3C promotes p53-mediated cell death in ALS by upregulating USP10 and promoting lnc-NR3C-triggered p53 activation, resulting in cell death. Conversely, lnc-NR3C knockdown inhibited USP10-triggered p53 activation, thereby protecting cells against oxidative stress. As a competitive endogenous RNA, lnc-NR3C competitively binds miR-129-5p, regulating the usp10/p53 axis. Elucidating the link between Lnc-NR3C and the USP10/p53 axis in an ALS cell model reveals a role for long non-coding RNAs in activating apoptosis. This provides new therapeutic opportunities in ALS.}, } @article {pmid38386047, year = {2024}, author = {Imrell, S and Fang, F and Ingre, C and Sennfält, S}, title = {Increased incidence of motor neuron disease in Sweden: a population-based study during 2002-2021.}, journal = {Journal of neurology}, volume = {271}, number = {5}, pages = {2730-2735}, pmid = {38386047}, issn = {1432-1459}, support = {Swedish Research Grant DNR 2019-01088//Vetenskapsrådet/ ; }, mesh = {Humans ; Sweden/epidemiology ; Male ; Female ; Incidence ; Aged ; *Motor Neuron Disease/epidemiology ; Middle Aged ; Aged, 80 and over ; Adult ; *Registries ; Young Adult ; Adolescent ; }, abstract = {BACKGROUND: Motor neuron diseases (MND), with amyotrophic lateral sclerosis constituting most cases, are rare conditions of unknown etiology. There have been reports of an increase in incidence during the latter half of the twentieth century in various Western countries, including Sweden. This study provides updated data on the incidence of MND in Sweden during the last 20 years.

METHODS: Data was obtained from the Swedish National Patient Register on individuals diagnosed with MND from 2002 to 2021 and analysed in relation to group level data for the entire Swedish population. Incidence rates were calculated and presented in relation to year, age, sex, and region.

RESULTS: In the early 2000s, there was a crude incidence rate of 3.5-3.7 per 100,000 person-years, which then increased to 4.0-4.6 from 2008 onward. Age standardization to the starting year (2002) partially mitigated this increase. The incidence rate was greater among men compared to women and was highest within the age range of 70 to 84 years. There were indications of a higher incidence rate in the northernmost parts of the country, although the difference was not statistically significant.

CONCLUSIONS: The incidence rate of MND in Sweden now seems to have surpassed 4 cases per 100,000 person-years. This is higher when compared to both other European countries and previous Swedish studies. It remains to be determined if this increase reflects an actual increasing incidence of MND in Sweden or is due to other factors such as better registry coverage.}, } @article {pmid38385052, year = {2024}, author = {Cherin, N and Patel, S and Jukic, M}, title = {Delayed amyotrophic lateral sclerosis diagnosis with subtle cardiac manifestations: Was anchoring bias contributory?.}, journal = {Clinical case reports}, volume = {12}, number = {2}, pages = {e8544}, pmid = {38385052}, issn = {2050-0904}, abstract = {Amyotrophic lateral sclerosis (ALS) is a rare, progressive neurodegenerative disease affecting both upper and lower motor neurons. Throughout medical training, it is taught that the most recognizable clinical presentation involves both motor and bulbar changes. Given the complexity of the diagnosis however, it is no surprise that there is significant multisystem involvement secondary to the autonomic dysfunction associated with the disease. The clinical cognitive biases that exist due to prior educational training and patient provided chief complaint can mislead clinicians and prevent a holistic, inclusive approach toward each patient encounter. This can delay diagnosis and increase unnecessary healthcare spending. In a disease with such a poor prognosis, this effect can be catastrophic, resulting in unacceptable medical, functional, and psychosocial outcomes. As clinicians, it is imperative to acknowledge these cognitive biases through introspection, which can improve clinical outcomes and ultimately patient quality of life for those facing this devastating disease. We report a case of a 55-year-old female who presented with a chief complaint of palpitations and minimal slurred speech on multiple encounters, subsequently leading to a focused cardiovascular workup. It was not until after several hospital encounters that a thorough functional and neuromuscular exam was performed, which ultimately helped to broaden the differential and lead to the diagnosis of ALS. Unfortunately, due to this delayed diagnosis, the patient's functionality was beyond repair. Given the underlying cognitive biases that are present in all clinicians, we hypothesize this patient's sex, presenting symptom, and primary chief complaint misled clinicians to perform limited history and physical examinations, therefore, leading to a narrowed differential. If diagnosed in a timely fashion, vital services such as rehabilitation could have provided this patient with the necessary medical, functional, and psychosocial support to face this devastating disease.}, } @article {pmid38384337, year = {2024}, author = {Wiesenfarth, M and Dorst, J and Brenner, D and Elmas, Z and Parlak, Ö and Uzelac, Z and Kandler, K and Mayer, K and Weiland, U and Herrmann, C and Schuster, J and Freischmidt, A and Müller, K and Siebert, R and Bachhuber, F and Simak, T and Günther, K and Fröhlich, E and Knehr, A and Regensburger, M and German, A and Petri, S and Grosskreutz, J and Klopstock, T and Reilich, P and Schöberl, F and Hagenacker, T and Weyen, U and Günther, R and Vidovic, M and Jentsch, M and Haarmeier, T and Weydt, P and Valkadinov, I and Hesebeck-Brinckmann, J and Conrad, J and Weishaupt, JH and Schumann, P and Körtvélyessy, P and Meyer, T and Ruf, WP and Witzel, S and Senel, M and Tumani, H and Ludolph, AC}, title = {Effects of tofersen treatment in patients with SOD1-ALS in a "real-world" setting - a 12-month multicenter cohort study from the German early access program.}, journal = {EClinicalMedicine}, volume = {69}, number = {}, pages = {102495}, pmid = {38384337}, issn = {2589-5370}, abstract = {BACKGROUND: In April 2023, the antisense oligonucleotide tofersen was approved by the U.S. Food and Drug Administration (FDA) for treatment of SOD1-amyotrophic lateral sclerosis (ALS), after a decrease of neurofilament light chain (NfL) levels had been demonstrated.

METHODS: Between 03/2022 and 04/2023, 24 patients with SOD1-ALS from ten German ALS reference centers were followed-up until the cut-off date for ALS functional rating scale revised (ALSFRS-R), progression rate (loss of ALSFRS-R/month), NfL, phosphorylated neurofilament heavy chain (pNfH) in cerebrospinal fluid (CSF), and adverse events.

FINDINGS: During the observation period, median ALSFRS-R decreased from 38.0 (IQR 32.0-42.0) to 35.0 (IQR 29.0-42.0), corresponding to a median progression rate of 0.11 (IQR -0.09 to 0.32) points of ALSFRS-R lost per month. Median serum NfL declined from 78.0 pg/ml (IQR 37.0-147.0 pg/ml; n = 23) to 36.0 pg/ml (IQR 22.0-65.0 pg/ml; n = 23; p = 0.02), median pNfH in CSF from 2226 pg/ml (IQR 1061-6138 pg/ml; n = 18) to 1151 pg/ml (IQR 521-2360 pg/ml; n = 18; p = 0.02). In the CSF, we detected a pleocytosis in 73% of patients (11 of 15) and an intrathecal immunoglobulin synthesis (IgG, IgM, or IgA) in 9 out of 10 patients. Two drug-related serious adverse events were reported.

INTERPRETATION: Consistent with the VALOR study and its Open Label Extension (OLE), our results confirm a reduction of NfL serum levels, and moreover show a reduction of pNfH in CSF. The therapy was safe, as no persistent symptoms were observed. Pleocytosis and Ig synthesis in CSF with clinical symptoms related to myeloradiculitis in two patients, indicate the potential of an autoimmune reaction.

FUNDING: No funding was received towards this study.}, } @article {pmid38383591, year = {2024}, author = {Verheijen, BM and Chung, C and Thompson, B and Kim, H and Nakahara, A and Anink, JJ and Mills, JD and , and Lee, JH and Aronica, E and Oyanagi, K and Kakita, A and Gout, JF and Vermulst, M}, title = {The cycad genotoxin methylazoxymethanol, linked to Guam ALS/PDC, induces transcriptional mutagenesis.}, journal = {Acta neuropathologica communications}, volume = {12}, number = {1}, pages = {30}, pmid = {38383591}, issn = {2051-5960}, support = {R01 AG054641/AG/NIA NIH HHS/United States ; R01 AG083065/AG/NIA NIH HHS/United States ; R01AG054641/AG/NIA NIH HHS/United States ; }, mesh = {Humans ; *Mutagens ; Guam ; Methylazoxymethanol Acetate/*analogs & derivatives ; Mutagenesis ; *Amyotrophic Lateral Sclerosis/genetics ; }, } @article {pmid38383503, year = {2024}, author = {Vidovic, M and Menschikowski, M and Freigang, M and Lapp, HS and Günther, R}, title = {Macrophage inclusions in cerebrospinal fluid following treatment initiation with antisense oligonucleotide therapies in motor neuron diseases.}, journal = {Neurological research and practice}, volume = {6}, number = {1}, pages = {11}, pmid = {38383503}, issn = {2524-3489}, abstract = {5q-associated spinal muscular atrophy (SMA) and amyotrophic lateral sclerosis (ALS) are two distinct neurological disorders leading to degeneration of lower motor neurons. The antisense oligonucleotides (ASOs) nusinersen and tofersen are novel disease-modifying agents for these diseases, respectively. In the context of ASO treatment, the cytological characteristics and composition of cerebrospinal fluid (CSF) have recently garnered particular interest. This report presents a case series of CSF cytology findings in two patients with SMA and ALS revealing comparable unspecified macrophage inclusions following treatment initiation with nusinersen and tofersen. Yet, the presence of these "asophages" in the treatment course of two different ASOs is of unclear significance. While both treatments have been well tolerated, this phenomenon warrants attention, given the long-term nature of these treatments.}, } @article {pmid38383499, year = {2024}, author = {Halcrow, PW and Quansah, DNK and Kumar, N and Steiner, JP and Nath, A and Geiger, JD}, title = {HERV-K (HML-2) Envelope Protein Induces Mitochondrial Depolarization and Neurotoxicity via Endolysosome Iron Dyshomeostasis.}, journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, volume = {44}, number = {14}, pages = {}, pmid = {38383499}, issn = {1529-2401}, support = {R01 NS065957/NS/NINDS NIH HHS/United States ; U54 GM115458/GM/NIGMS NIH HHS/United States ; R01 MH119000/MH/NIMH NIH HHS/United States ; R01 DA032444/DA/NIDA NIH HHS/United States ; R01 GM100329/GM/NIGMS NIH HHS/United States ; ZIA NS003130/ImNIH/Intramural NIH HHS/United States ; }, mesh = {Humans ; *Endogenous Retroviruses ; *Amyotrophic Lateral Sclerosis/pathology ; Iron ; Reactive Oxygen Species ; *Neuroblastoma ; *Neurotoxicity Syndromes ; Arginine ; }, abstract = {Human endogenous retroviruses (HERVs) are associated with the pathogenesis of amyotrophic lateral sclerosis (ALS); a disease characterized by motor neuron degeneration and cell death. The HERV-K subtype HML-2 envelope protein (HERV-K Env) is expressed in the brain, spinal cord, and cerebrospinal fluid of people living with ALS and through CD98 receptor-linked interactions causes neurodegeneration. HERV-K Env-induced increases in oxidative stress are implicated in the pathogenesis of ALS, and ferrous iron (Fe[2+]) generates reactive oxygen species (ROS). Endolysosome stores of Fe[2+] are central to iron trafficking and endolysosome deacidification releases Fe[2+] into the cytoplasm. Because HERV-K Env is an arginine-rich protein that is likely endocytosed and arginine is a pH-elevating amino acid, it is important to determine HERV-K Env effects on endolysosome pH and whether HERV-K Env-induced neurotoxicity is downstream of Fe[2+] released from endolysosomes. Here, we showed using SH-SY5Y human neuroblastoma cells and primary cultures of human cortical neurons (HCNs, information on age and sex was not available) that HERV-K Env (1) is endocytosed via CD98 receptors, (2) concentration dependently deacidified endolysosomes, (3) decreased endolysosome Fe[2+] concentrations, (4) increased cytosolic and mitochondrial Fe[2+] and ROS levels, (5) depolarized mitochondrial membrane potential, and (6) induced cell death, effects blocked by an antibody against the CD98 receptor and by the endolysosome iron chelator deferoxamine. Thus, HERV-K Env-induced increases in cytosolic and mitochondrial Fe[2+] and ROS as well as cell death appear to be mechanistically caused by HERV-K Env endocytosis, endolysosome deacidification, and endolysosome Fe[2+] efflux into the cytoplasm.}, } @article {pmid38382884, year = {2024}, author = {Jiao, LL and Dong, HL and Liu, MM and Wu, PL and Cao, Y and Zhang, Y and Gao, FG and Zhu, HY}, title = {The potential roles of salivary biomarkers in neurodegenerative diseases.}, journal = {Neurobiology of disease}, volume = {193}, number = {}, pages = {106442}, doi = {10.1016/j.nbd.2024.106442}, pmid = {38382884}, issn = {1095-953X}, mesh = {Humans ; *Neurodegenerative Diseases/diagnosis ; Reproducibility of Results ; *Parkinson Disease/metabolism ; *Alzheimer Disease ; *Huntington Disease/diagnosis ; Biomarkers ; }, abstract = {Current research efforts on neurodegenerative diseases are focused on identifying novel and reliable biomarkers for early diagnosis and insight into disease progression. Salivary analysis is gaining increasing interest as a promising source of biomarkers and matrices for measuring neurodegenerative diseases. Saliva collection offers multiple advantages over the currently detected biofluids as it is easily accessible, non-invasive, and repeatable, allowing early diagnosis and timely treatment of the diseases. Here, we review the existing findings on salivary biomarkers and address the potential value in diagnosing neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, Huntington's disease and Amyotrophic lateral sclerosis. Based on the available research, β-amyloid, tau protein, α-synuclein, DJ-1, Huntington protein in saliva profiles display reliability and validity as the biomarkers of neurodegenerative diseases.}, } @article {pmid38382647, year = {2024}, author = {Huang, TN and Shih, YT and Yen, TL and Hsueh, YP}, title = {Vcp overexpression and leucine supplementation extend lifespan and ameliorate neuromuscular junction phenotypes of a SOD1G93A-ALS mouse model.}, journal = {Human molecular genetics}, volume = {33}, number = {11}, pages = {935-944}, pmid = {38382647}, issn = {1460-2083}, support = {AS-CFII-108-104//Transgenic Core Facility/ ; //Animal Facility of the Institute of Molecular Biology, Academia Sinica/ ; }, mesh = {Animals ; *Valosin Containing Protein/metabolism/genetics ; *Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology ; *Disease Models, Animal ; Mice ; *Neuromuscular Junction/metabolism ; Female ; Male ; *Longevity/genetics ; *Mice, Transgenic ; *Leucine/pharmacology/metabolism ; *Superoxide Dismutase-1/genetics/metabolism ; *Phenotype ; Superoxide Dismutase/genetics/metabolism ; Cell Cycle Proteins/genetics/metabolism ; Humans ; Adenosine Triphosphatases/genetics/metabolism ; }, abstract = {Many genes with distinct molecular functions have been linked to genetically heterogeneous amyotrophic lateral sclerosis (ALS), including SuperOxide Dismutase 1 (SOD1) and Valosin-Containing Protein (VCP). SOD1 converts superoxide to oxygen and hydrogen peroxide. VCP acts as a chaperon to regulate protein degradation and synthesis and various other cellular responses. Although the functions of these two genes differ, in the current report we show that overexpression of wild-type VCP in mice enhances lifespan and maintains the size of neuromuscular junctions (NMJs) of both male and female SOD1G93A mice, a well-known ALS mouse model. Although VCP exerts multiple functions, its regulation of ER formation and consequent protein synthesis has been shown to play the most important role in controlling dendritic spine formation and social and memory behaviors. Given that SOD1 mutation results in protein accumulation and aggregation, it may direct VCP to the protein degradation pathway, thereby impairing protein synthesis. Since we previously showed that the protein synthesis defects caused by Vcp deficiency can be improved by leucine supplementation, to confirm the role of the VCP-protein synthesis pathway in SOD1-linked ALS, we applied leucine supplementation to SOD1G93A mice and, similar to Vcp overexpression, we found that it extends SOD1G93A mouse lifespan. In addition, the phenotypes of reduced muscle strength and fewer NMJs of SOD1G93A mice are also improved by leucine supplementation. These results support the existence of crosstalk between SOD1 and VCP and suggest a critical role for protein synthesis in ASL. Our study also implies a potential therapeutic treatment for ALS.}, } @article {pmid38382562, year = {2024}, author = {Berezutskyi, V and Berezutska, M}, title = {Rare Example of abnormal vocal resonance: a case from Balzac's novel.}, journal = {Pneumologie (Stuttgart, Germany)}, volume = {78}, number = {8}, pages = {556-560}, doi = {10.1055/a-2248-9672}, pmid = {38382562}, issn = {1438-8790}, mesh = {Adolescent ; Humans ; Male ; Diagnosis, Differential ; Rare Diseases ; *Singing ; Tuberculosis, Pulmonary/diagnosis ; Voice Disorders/diagnosis/etiology ; Medicine in Literature ; }, abstract = {Ungewöhnliche klinische Fälle wecken bei praktizierenden Ärzten immer wieder Interesse und ermöglichen es ihnen, ihre Wissensbasis zu erweitern und ihre Fähigkeiten zum klinischen Denken zu verbessern. Der Zweck dieser Studie besteht darin, einen klinischen Fall von Stimmresonanz beim Singen bei einem schwindsüchtigen Teenager aus dem Roman "Der Landarzt" von Honoré de Balzac unter Verwendung induktiver und deduktiver Methoden des klinischen Denkens zu analysieren. Stimmresonanzen beim Singen in Schwindsucht können als pathognomonisches Zeichen für eine kavernöse Tuberkulose gewertet werden, da nur mit dem Bronchus verbundene Hohlräume als Helmholtz-Resonator wirken. Trotz der Einzigartigkeit ist das Gehäuse durchaus realistisch, da es nicht im Widerspruch zu den Gesetzen der Akustik steht. Praktizierende Ärzte verfügen über die Kenntnisse der medizinischen Physik, Morphologie und Physiologie, die zum Verständnis der Pathogenese der klinischen Manifestation einer Lungenhöhle erforderlich sind. Dieser Fall zeigt deutlich die Vor- und Nachteile klinischer Denkmethoden, die in der Praxis eingesetzt werden. Dank der Kombination aus Originalität und Realismus kann der Fall von Stimmresonanz aus Balzacs Roman "Der Landarzt" seinen rechtmäßigen Platz in der persönlichen Sammlung klinischer Fälle eines jeden Lungenarztes einnehmen.}, } @article {pmid38382464, year = {2024}, author = {Smith, HL and Chaytow, H and Gillingwater, TH}, title = {Excitotoxicity and ALS: New therapy targets an old mechanism.}, journal = {Cell reports. Medicine}, volume = {5}, number = {2}, pages = {101423}, pmid = {38382464}, issn = {2666-3791}, mesh = {Animals ; Mice ; *Amyotrophic Lateral Sclerosis/drug therapy/genetics/metabolism ; Mice, Transgenic ; Motor Neurons/metabolism ; Superoxide Dismutase/metabolism ; Disease Models, Animal ; }, abstract = {Excitotoxicity-induced cell death in motor neurons is a major therapeutic target for amyotrophic lateral sclerosis (ALS). Yan et al.[1] present a novel compound to specifically disrupt extra-synaptic NMDAR complexes, extending the lifespan of the SOD1[G93A] ALS mouse and ameliorating cell death.}, } @article {pmid38381656, year = {2024}, author = {Wang, XX and Chen, WZ and Li, C and Xu, RS}, title = {Current potential pathogenic mechanisms of copper-zinc superoxide dismutase 1 (SOD1) in amyotrophic lateral sclerosis.}, journal = {Reviews in the neurosciences}, volume = {35}, number = {5}, pages = {549-563}, pmid = {38381656}, issn = {2191-0200}, mesh = {*Amyotrophic Lateral Sclerosis/metabolism/pathology/genetics ; Humans ; *Superoxide Dismutase-1/metabolism/genetics ; Animals ; Motor Neurons/metabolism/pathology ; Oxidative Stress/physiology ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a rare neurodegenerative disease which damages upper and lower motor neurons (UMN and LMN) innervating the muscles of the trunk, extremities, head, neck and face in cerebrum, brain stem and spinal cord, which results in the progressive weakness, atrophy and fasciculation of muscle innervated by the related UMN and LMN, accompanying with the pathological signs leaded by the cortical spinal lateral tract lesion. The pathogenesis about ALS is not fully understood, and no specific drugs are available to cure and prevent the progression of this disease at present. In this review, we reviewed the structure and associated functions of copper-zinc superoxide dismutase 1 (SOD1), discuss why SOD1 is crucial to the pathogenesis of ALS, and outline the pathogenic mechanisms of SOD1 in ALS that have been identified at recent years, including glutamate-related excitotoxicity, mitochondrial dysfunction, endoplasmic reticulum stress, oxidative stress, axonal transport disruption, prion-like propagation, and the non-cytologic toxicity of glial cells. This review will help us to deeply understand the current progression in this field of SOD1 pathogenic mechanisms in ALS.}, } @article {pmid38381447, year = {2024}, author = {Bahr, T and Vu, TA and Tuttle, JJ and Iezzi, R}, title = {Deep Learning and Machine Learning Algorithms for Retinal Image Analysis in Neurodegenerative Disease: Systematic Review of Datasets and Models.}, journal = {Translational vision science & technology}, volume = {13}, number = {2}, pages = {16}, pmid = {38381447}, issn = {2164-2591}, mesh = {Humans ; Algorithms ; *Alzheimer Disease/diagnostic imaging ; *Deep Learning ; Machine Learning ; *Neurodegenerative Diseases/diagnostic imaging ; Datasets as Topic ; *Retina/diagnostic imaging ; }, abstract = {PURPOSE: Retinal images contain rich biomarker information for neurodegenerative disease. Recently, deep learning models have been used for automated neurodegenerative disease diagnosis and risk prediction using retinal images with good results.

METHODS: In this review, we systematically report studies with datasets of retinal images from patients with neurodegenerative diseases, including Alzheimer's disease, Huntington's disease, Parkinson's disease, amyotrophic lateral sclerosis, and others. We also review and characterize the models in the current literature which have been used for classification, regression, or segmentation problems using retinal images in patients with neurodegenerative diseases.

RESULTS: Our review found several existing datasets and models with various imaging modalities primarily in patients with Alzheimer's disease, with most datasets on the order of tens to a few hundred images. We found limited data available for the other neurodegenerative diseases. Although cross-sectional imaging data for Alzheimer's disease is becoming more abundant, datasets with longitudinal imaging of any disease are lacking.

CONCLUSIONS: The use of bilateral and multimodal imaging together with metadata seems to improve model performance, thus multimodal bilateral image datasets with patient metadata are needed. We identified several deep learning tools that have been useful in this context including feature extraction algorithms specifically for retinal images, retinal image preprocessing techniques, transfer learning, feature fusion, and attention mapping. Importantly, we also consider the limitations common to these models in real-world clinical applications.

TRANSLATIONAL RELEVANCE: This systematic review evaluates the deep learning models and retinal features relevant in the evaluation of retinal images of patients with neurodegenerative disease.}, } @article {pmid38381392, year = {2024}, author = {Miah, MM and Zinnia, MA and Tabassum, N and Islam, ABMMK}, title = {Association between DPP6 gene rs10260404 polymorphism and increased risk of sporadic amyotrophic lateral sclerosis (sALS): a meta-analysis.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {45}, number = {7}, pages = {3225-3243}, pmid = {38381392}, issn = {1590-3478}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/epidemiology ; *Genetic Predisposition to Disease/genetics ; *Dipeptidyl-Peptidases and Tripeptidyl-Peptidases/genetics ; *Polymorphism, Single Nucleotide ; Case-Control Studies ; Nerve Tissue Proteins ; Potassium Channels ; }, abstract = {BACKGROUND: Sporadic amyotrophic lateral sclerosis (sALS) is a severe neurodegenerative disease characterized by continuous diminution of motor neurons in the brain and spinal cord. Earlier studies indicated that the DPP6 gene variant has a role in the development of sALS. This meta-analysis was designed to uncover the role of rs10260404 polymorphism of the DPP6 gene and its association with sALS.

METHODS: All case-control articles published prior to October 2022 on the association between DPP6 (rs10260404) polymorphism and sALS risk were systematically extracted from different databases which include PubMed, PubMed Central, and Google Scholar. Overall odds ratios (ORs) and "95% confidence intervals (CIs)" were summarized for various genetic models. Subgroup and heterogeneity assessments were performed. Egger's and "Begg's tests were applied to evaluate publication bias. Trial sequential analysis (TSA) and false-positive report probability (FPRP) were performed.

RESULTS: Nine case-control studies containing 4202 sALS cases and 4444 healthy controls were included in the meta-analysis. A significant association of the DPP6 (rs10260404) variant with an increased sALS risk in overall pooled subjects under allelic model [C allele vs. T allele, OR = 1.149, 95% CI (1.010-1.307), p-value = 0.035], dominant model [CC + CT vs. TT, OR = 1.165, 95% CI (1.067-1.273), p-value = 0.001], and homozygote comparison [CC vs. TT, OR = 1.421, 95% CI (1.003-2.011), p-value = 0.048] were observed. Moreover, in subgroup analysis by nationality, remarkable associations were detected in Dutch, Irish, American, and Swedish under allelic, dominant, and homozygote models. Additionally, stratification analysis by ethnicity exhibited an association with sALS risk among Caucasians and Americans under different genetic models. Interestingly, none of the models found any significant association with Asians.

CONCLUSION: The present meta-analysis indicates that DPP6 (rs10260404) polymorphism could be a candidate risk factor for sALS predisposition.}, } @article {pmid38381071, year = {2024}, author = {Scherer, NM and Maurel, C and Graus, MS and McAlary, L and Richter, G and Radford, RAW and Hogan, A and Don, EK and Lee, A and Yerbury, J and Francois, M and Chung, RS and Morsch, M}, title = {RNA-binding properties orchestrate TDP-43 homeostasis through condensate formation in vivo.}, journal = {Nucleic acids research}, volume = {52}, number = {9}, pages = {5301-5319}, pmid = {38381071}, issn = {1362-4962}, support = {//Bill Gole Postdoctoral Fellowship/ ; //Motor Neuron Disease Research Australia/ ; //FightMND funding/ ; R21DA056320/NS/NINDS NIH HHS/United States ; //Snow Foundation Fellowship/ ; /MH/NIMH NIH HHS/United States ; //Macquarie University/ ; //Snow Foundation/ ; //National Health and Medical Research Council/ ; //NHMRC/ ; R21 DA056320/DA/NIDA NIH HHS/United States ; //ALS Foundation Netherlands/ ; }, mesh = {Animals ; Humans ; Mice ; Amyotrophic Lateral Sclerosis/metabolism/genetics ; Biomolecular Condensates/metabolism ; Cell Nucleus/metabolism ; *DNA-Binding Proteins/metabolism/genetics ; Homeostasis ; *Motor Neurons/metabolism ; Mutation ; Protein Binding ; Protein Processing, Post-Translational ; RNA/metabolism/genetics ; *RNA-Binding Proteins/metabolism/genetics ; }, abstract = {Insoluble cytoplasmic aggregate formation of the RNA-binding protein TDP-43 is a major hallmark of neurodegenerative diseases including Amyotrophic Lateral Sclerosis. TDP-43 localizes predominantly in the nucleus, arranging itself into dynamic condensates through liquid-liquid phase separation (LLPS). Mutations and post-translational modifications can alter the condensation properties of TDP-43, contributing to the transition of liquid-like biomolecular condensates into solid-like aggregates. However, to date it has been a challenge to study the dynamics of this process in vivo. We demonstrate through live imaging that human TDP-43 undergoes nuclear condensation in spinal motor neurons in a living animal. RNA-binding deficiencies as well as post-translational modifications can lead to aberrant condensation and altered TDP-43 compartmentalization. Single-molecule tracking revealed an altered mobility profile for RNA-binding deficient TDP-43. Overall, these results provide a critically needed in vivo characterization of TDP-43 condensation, demonstrate phase separation as an important regulatory mechanism of TDP-43 accessibility, and identify a molecular mechanism of how functional TDP-43 can be regulated.}, } @article {pmid38380436, year = {2024}, author = {Nakaso, K}, title = {Roles of Microglia in Neurodegenerative Diseases.}, journal = {Yonago acta medica}, volume = {67}, number = {1}, pages = {1-8}, pmid = {38380436}, issn = {0513-5710}, abstract = {In recent years, microglia have attracted attention owing to their roles in various neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. Microglia, which are brain-resident macrophages, not only act as immune cells but also perform other functions in the body. Interestingly, they exert contrasting effects on different neurodegenerative diseases. In addition to the previously reported M1 (toxic) and M2 (protective) types, microglia now also include disease-associated microglia owing to a more elaborate classification. Understanding this detailed classification is necessary to elucidate the association between microglia and neurodegenerative diseases. In this review, we discuss the diverse roles of microglia in neurodegenerative diseases and highlight their potential as therapeutic targets.}, } @article {pmid38379946, year = {2024}, author = {El-Mastouri, Z and Košnarová, P and Hamouzová, K and Alimi, E and Soukup, J}, title = {Insight into the herbicide resistance patterns in Lolium rigidum populations in Tunisian and Moroccan wheat regions.}, journal = {Frontiers in plant science}, volume = {15}, number = {}, pages = {1331725}, pmid = {38379946}, issn = {1664-462X}, abstract = {Rigid ryegrass (Lolium rigidum Gaud.) is one of the most troublesome weeds in Moroccan and Tunisian cereal crop fields. In total, 19 rigid ryegrass field populations were randomly selected in northern wheat crop areas of Morocco and Tunisia to examine the patterns of herbicide resistance to acetolactate synthase (ALS)- and acetyl-CoA carboxylase (ACCase)-inhibiting herbicides. Greenhouse experiments confirmed reduced sensitivity to ALS- and/or ACCase-inhibiting herbicides in all L. rigidum populations. The occurrence of target-site resistance (TSR) was tested using high-throughput genotyping. The advent of next-generation sequencing (NGS) has enabled easy identification of causal mutations and confirmed the presence of ALS and ACCase mutations at specific codons conferring TSR. Thirteen populations showed resistance to ALS-inhibiting herbicides associated with point mutations in positions Pro-197-Thr, Pro-197-Ser, Pro-197-Leu, Pro-197-Gln and Trp-574-Leu, while resistance to ACCase-inhibiting herbicides was detected in 18 populations in positions Asp-2078-Val, Trp-2027-Cys, Ile-1781-Leu, Gly-2096-Ala, and Ile-2041-Asn of the enzymes conferring TSR. Additionally, dose-response experiments with pyroxsulam applied after the inhibition of cytochrome P450 monooxygenase by malathion showed an increase in sensitivity in two out of seven highly resistant (HR) rigid ryegrass populations. This demonstrates the presence of non-target-site resistance (NTSR) in some ryegrass populations. Further evidence of NTSR was investigated in dose-response experiments with pyroxsulam, following pretreatment with the glutathione S-transferase (GST) inhibitor 4-chloro-7-nitrobenzoxadiazole (NBD-Cl), which partially reversed resistance in only a few individuals of two L. rigidum populations. Hence, our study confirms the existence of multiple and cross-resistance to ALS- and ACCase-inhibiting herbicides in L. rigidum from Morocco and Tunisia with both TSR and NTSR mechanisms. These results emphasize local resistance management as an important tool to detect and mitigate gene flow from rigid ryegrass populations where resistance has evolved.}, } @article {pmid38378992, year = {2024}, author = {Song, M and Qiang, Y and Zhao, X and Song, F}, title = {Cyclin-dependent Kinase 5 and Neurodegenerative Diseases.}, journal = {Molecular neurobiology}, volume = {61}, number = {10}, pages = {7287-7302}, pmid = {38378992}, issn = {1559-1182}, mesh = {Humans ; *Neurodegenerative Diseases/enzymology/metabolism ; *Cyclin-Dependent Kinase 5/metabolism ; Animals ; Oxidative Stress/physiology ; Mitochondria/metabolism ; }, abstract = {Neurodegenerative diseases are a group of diseases characterized by the progressive loss of neurons, including Alzheimer's disease, Parkinson's disease, and Amyotrophic lateral sclerosis. These diseases have a high incidence and mortality rate globally, placing a heavy burden on patients and their families. The pathogenesis of neurodegenerative diseases is complex, and there are no effective treatments at present. Cyclin-dependent kinase 5 is a proline-directed serine/threonine protein kinase that is closely related to the development and function of the nervous system. Under physiological conditions, it is involved in regulating the process of neuronal proliferation, differentiation, migration, and synaptic plasticity. Moreover, there is increasing evidence that cyclin-dependent kinase 5 also plays an important role in the pathogenesis of neurodegenerative diseases. In this review, we address the biological characteristics of cyclin-dependent kinase 5 and its role in neurodegenerative diseases. In particular, this review highlights the underlying mechanistic linkages between cyclin-dependent kinase 5 and mitochondrial dysfunction, oxidative stress and neuroinflammation in the context of neurodegeneration. Finally, we also summarize the currently available cyclin-dependent kinase 5 inhibitors and their prospects for the treatment of neurodegenerative diseases. Taken together, a better understanding of the molecular mechanisms of cyclin-dependent kinase 5 involved in neurodegenerative diseases can lead to the development of new strategies for the prevention and treatment of these devastating diseases.}, } @article {pmid38378788, year = {2024}, author = {Rim, C and You, MJ and Nahm, M and Kwon, MS}, title = {Emerging role of senescent microglia in brain aging-related neurodegenerative diseases.}, journal = {Translational neurodegeneration}, volume = {13}, number = {1}, pages = {10}, pmid = {38378788}, issn = {2047-9158}, support = {2023R1A2C1006622//National Research Foundation (NRF)/ ; RS-2023-00265515//National Research Foundation (NRF)/ ; }, mesh = {Humans ; *Neurodegenerative Diseases/pathology ; Microglia/pathology ; Brain/pathology ; Cellular Senescence ; *Amyotrophic Lateral Sclerosis/pathology ; }, abstract = {Brain aging is a recognized risk factor for neurodegenerative diseases like Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis (ALS, Lou Gehrig's disease), but the intricate interplay between brain aging and the pathogenesis of these conditions remains inadequately understood. Cellular senescence is considered to contribute to cellular dysfunction and inflammaging. According to the threshold theory of senescent cell accumulation, the vulnerability to neurodegenerative diseases is associated with the rates of senescent cell generation and clearance within the brain. Given the role of microglia in eliminating senescent cells, the accumulation of senescent microglia may lead to the acceleration of brain aging, contributing to inflammaging and increased vulnerability to neurodegenerative diseases. In this review, we propose the idea that the senescence of microglia, which is notably vulnerable to aging, could potentially serve as a central catalyst in the progression of neurodegenerative diseases. The senescent microglia are emerging as a promising target for mitigating neurodegenerative diseases.}, } @article {pmid38378504, year = {2024}, author = {Pollmann, AS and Nguyen, MTD and Keyeutat, M and Danis, É and Durr, GM and Agoumi, Y and Jabbour, S}, title = {Refractive outcomes of immediately sequential bilateral cataract surgery in eyes with long and short axial lengths.}, journal = {BMC ophthalmology}, volume = {24}, number = {1}, pages = {77}, pmid = {38378504}, issn = {1471-2415}, mesh = {Humans ; Visual Acuity ; Lens Implantation, Intraocular/adverse effects ; Retrospective Studies ; *Lenses, Intraocular/adverse effects ; Refraction, Ocular ; *Refractive Errors/etiology ; Biometry ; Axial Length, Eye ; *Cataract/complications ; *Cataract Extraction/adverse effects ; }, abstract = {PURPOSE: To report the refractive outcomes of long (≥25.00 mm) and short (≤22.00 mm) axial length (AL) eyes undergoing immediately sequential bilateral cataract surgery (ISBCS).

METHODS: In this retrospective cohort study, patients who underwent ISBCS were identified and eyes of patients with bilateral long and short ALs were included. Pre- and postoperative biometry, autorefraction, and ocular comorbidities or complications were recorded. The primary outcome was the mean refractive prediction error.

RESULTS: Thirty-seven patients (74 eyes) with long ALs and 18 patients (36 eyes) with short ALs were included. The means ± standard deviations of the ALs were 26.40 ± 1.38 mm and 21.44 ± 0.46 mm in the long and short AL groups, respectively. In long AL eyes, the mean absolute error from the biometry-predicted refraction was - 0.16 ± 0.46 D, corresponding to 74% of eyes achieving a refraction within ±0.50 D of the predicted value. In short AL eyes, the mean absolute error was - 0.63 ± 0.73 D, corresponding to 44% of eyes achieving a refraction within ±0.50 D of the predicted value. Eight (44.4%) patients with short AL eyes had a myopic deviation greater than ±0.50 D from the predicted result in both eyes.

CONCLUSIONS: Compared to patients with long AL eyes, ISBCS in patients with short ALs had a wider variance in refractive outcome and a lower rate of achieving a postoperative refraction within ±0.50 D of the predicted target.}, } @article {pmid38377980, year = {2024}, author = {Ariana, S and Amjadi, N and Kazemi, SN and Ahmadli, Z}, title = {The Use of Evening Primrose Oil for Cervical Ripening in Low-Risk Women with Term Pregnancy: A Randomized Double-Blinded Controlled Trial.}, journal = {Complementary medicine research}, volume = {31}, number = {3}, pages = {215-221}, doi = {10.1159/000535585}, pmid = {38377980}, issn = {2504-2106}, mesh = {Humans ; Female ; Pregnancy ; Adult ; Double-Blind Method ; *Plant Oils/therapeutic use ; *Oenothera biennis ; *gamma-Linolenic Acid/therapeutic use/administration & dosage ; *Linoleic Acids/therapeutic use ; *Cervical Ripening/drug effects ; Young Adult ; Iran ; }, abstract = {BACKGROUND: Several methods have been developed for cervical ripening. The data regarding the efficiency of evening primrose oil (EPO) are inconsistent. The purpose of this study was to investigate the outcomes of EPO use on cervical ripening in low-risk women with term pregnancy.

PATIENTS AND METHODS: Low-risk term pregnant women referred to the obstetrics clinic of Imam Hossein Hospital in Tehran who were eligible according to the inclusion were randomized either to the case or control group. The case group received 1,000 mg vaginal EPO capsule, and the other group received a vaginal placebo capsule daily, similar to the original drug. The primary outcome was Bishop score, while the duration of labor phases and the inducing procedures were the secondary outcomes.

RESULTS: Forty-eight participants were randomized to each group and were considered for data analysis. Although Bishop score was not statistically different before the intervention, it was significantly higher in case group compared to the placebo group after the intervention (EPO = 5.83 ± 1.68, placebo = 5.19 ± 1.52, p value = 0.002). Four participants in the case group and two in the control group underwent cesarean section (p value = 0.677). The need for labor induction was significantly higher in the placebo group than EPO group (oxytocin injection: 10.4% vs. 31.3%, p value = 0.012, amniotomy: 75% vs. 41.7, p value = 0.001).

CONCLUSION: The vaginal use of EPO could be considered as a safe and efficient approach for cervical ripening in low-risk term pregnant women.

UNLABELLED: HintergrundEs wurden verschiedene Methoden zur Zervixreifung entwickelt. Die Daten zur Wirksamkeit von Nachtkerzenöl (evening primrose oil, EPO) sind uneinheitlich. Mit dieser Studie sollen die Ergebnisse der Anwendung von EPO zur Zervixreifung bei Frauen mit niedrigem Risiko und termingerechter Schwangerschaft untersucht werden.Patientinnen und MethodenSchwangere Frauen mit niedrigem Risiko und termingerechter Schwangerschaft, die in die Geburtsklinik des Imam-Hossein-Krankenhauses in Teheran eingewiesen wurden und gemäss den Einschlusskriterien für die Teilnahme infrage kamen, wurden randomisiert der Fall- oder der Kontrollgruppe zugewiesen. Die Fallgruppe erhielt 1.000 mg EPO als Vaginalkapseln, während die andere Gruppe täglich eine vaginale Placebokapsel erhielt, die dem Originalpräparat ähnelte. Primäres Zielkriterium war der Bishop-Score und sekundäre Zielkriterien waren die Dauer der Wehenphasen sowie die Verfahren zur Geburtseinleitung.ErgebnisseJeder Gruppe wurden randomisiert 48 Teilnehmerinnen zugewiesen und bei der Datenanalyse berücksichtigt. Während vor der Intervention kein statistisch signifikanter Unterschied im Bishop-Score bestand, fiel dieser nach der Intervention in der Fallgruppe signifikant höher aus als in der Placebogruppe (EPO = 5,83 ± 1,68, Placebo = 5,19 ± 1,52, p-Wert = 0,002). Bei vier Teilnehmerinnen in der Fallgruppe und zwei in der Kontrollgruppe wurde ein Kaiserschnitt durchgeführt (p-Wert = 0,677). Die Notwendigkeit einer Weheneinleitung war in der Placebogruppe signifikant höher als in der EPO-Gruppe (Oxytocin-Injektion: 10,4% vs. 31,3%, p-Wert = 0,012, Amniotomie: 75% vs. 41,7%, p-Wert = 0,001).SchlussfolgerungDie vaginale Anwendung von EPO kann als sicherer und wirksamer Ansatz zur Zervixreifung bei Frauen mit niedrigem Risiko und termingerechter Schwangerschaft angesehen werden.}, } @article {pmid38377779, year = {2024}, author = {Sapienza, S and Tedeschi, V and Apicella, B and Pannaccione, A and Russo, C and Sisalli, MJ and Magliocca, G and Loffredo, S and Secondo, A}, title = {Ultrafine particulate matter pollution and dysfunction of endoplasmic reticulum Ca[2+] store: A pathomechanism shared with amyotrophic lateral sclerosis motor neurons?.}, journal = {Ecotoxicology and environmental safety}, volume = {273}, number = {}, pages = {116104}, doi = {10.1016/j.ecoenv.2024.116104}, pmid = {38377779}, issn = {1090-2414}, mesh = {Animals ; Mice ; *Amyotrophic Lateral Sclerosis/chemically induced/genetics/metabolism ; Endoplasmic Reticulum/metabolism ; Motor Neurons/metabolism ; Proteomics ; Primary Cell Culture ; *Particulate Matter/adverse effects ; Endoplasmic Reticulum Stress ; Calcium/metabolism ; Disease Models, Animal ; }, abstract = {Increased risk of neurodegenerative diseases has been envisaged for air pollution exposure. On the other hand, environmental risk factors, including air pollution, have been suggested for Amyotrophic Lateral Sclerosis (ALS) pathomechanism. Therefore, the neurotoxicity of ultrafine particulate matter (PM0.1) (PM < 0.1 μm size) and its sub-20 nm nanoparticle fraction (NP20) has been investigated in motor neuronal-like cells and primary cortical neurons, mainly affected in ALS. The present data showed that PM0.1 and NP20 exposure induced endoplasmic reticulum (ER) stress, as occurred in cortex and spinal cord of ALS mice carrying G93A mutation in SOD1 gene. Furthermore, NSC-34 motor neuronal-like cells exposed to PM0.1 and NP20 shared the same proteomic profile on some apoptotic factors with motor neurons treated with the L-BMAA, a neurotoxin inducing Amyotrophic Lateral Sclerosis/Parkinson-Dementia Complex (ALS/PDC). Of note ER stress induced by PM0.1 and NP20 in motor neurons was associated to pathological changes in ER morphology and dramatic reduction of organellar Ca[2+] level through the dysregulation of the Ca[2+]-pumps SERCA2 and SERCA3, the Ca[2+]-sensor STIM1, and the Ca[2+]-release channels RyR3 and IP3R3. Furthermore, the mechanism deputed to ER Ca[2+] refilling (e.g. the so called store operated calcium entry-SOCE) and the relative currents ICRAC were also altered by PM0.1 and NP20 exposure. Additionally, these carbonaceous particles caused the exacerbation of L-BMAA-induced ER stress and Caspase-9 activation. In conclusion, this study shows that PM0.1 and NP20 induced the aberrant expression of ER proteins leading to dysmorphic ER, organellar Ca[2+] dysfunction, ER stress and neurotoxicity, providing putative correlations with the neurodegenerative process occurring in ALS.}, } @article {pmid38377583, year = {2024}, author = {Zhao, S and Solem, C}, title = {Thiamine-Starved Lactococcus lactis for Producing Food-Grade Pyruvate.}, journal = {Journal of agricultural and food chemistry}, volume = {72}, number = {9}, pages = {4858-4868}, doi = {10.1021/acs.jafc.3c09216}, pmid = {38377583}, issn = {1520-5118}, mesh = {*Pyruvic Acid/metabolism ; *Lactococcus lactis/genetics/metabolism ; Thiamine/metabolism ; Diacetyl/metabolism ; L-Lactate Dehydrogenase/metabolism ; Lactic Acid/metabolism ; Butter ; *Lactates ; }, abstract = {Lactococcus lactis is a safe lactic acid bacterium widely used in dairy fermentations. Normally, its main fermentation product is lactic acid; however, L. lactis can be persuaded into producing other compounds, e.g., through genetic engineering. Here, we have explored the possibility of rewiring the metabolism of L. lactis into producing pyruvate without using genetic tools. Depriving the thiamine-auxotrophic and lactate dehydrogenase-deficient L. lactis strain RD1M5 of thiamine efficiently shut down two enzymes at the pyruvate branch, the thiamine pyrophosphate (TPP) dependent pyruvate dehydrogenase (PDHc) and α-acetolactate synthase (ALS). After eliminating the remaining enzyme acting on pyruvate, the highly oxygen-sensitive pyruvate formate lyase (PFL), by simple aeration, the outcome was pyruvate production. Pyruvate could be generated by nongrowing cells and cells growing in a substrate low in thiamine, e.g., Florisil-treated milk. Pyruvate is a precursor for the butter aroma compound diacetyl. Using an α-acetolactate decarboxylase deficient L. lactis strain, pyruvate could be converted to α-acetolactate and diacetyl. Summing up, by starving L. lactis for thiamine, secretion of pyruvate could be attained. The food-grade pyruvate produced has many applications, e.g., as an antioxidant or be used to make butter aroma.}, } @article {pmid38377183, year = {2024}, author = {Brar, S and Ganesh, S and Karegowda, M}, title = {Clinical outcomes and rotational stability after implantation of a monofocal toric intraocular lens with textured haptics in normal vs high axial lengths.}, journal = {Journal of cataract and refractive surgery}, volume = {50}, number = {7}, pages = {718-723}, doi = {10.1097/j.jcrs.0000000000001429}, pmid = {38377183}, issn = {1873-4502}, mesh = {Humans ; Retrospective Studies ; *Lens Implantation, Intraocular ; *Lenses, Intraocular ; *Visual Acuity/physiology ; Female ; *Phacoemulsification ; Male ; *Axial Length, Eye/pathology ; *Refraction, Ocular/physiology ; *Pseudophakia/physiopathology ; Middle Aged ; *Astigmatism/physiopathology/surgery ; Prosthesis Design ; Aged ; Rotation ; Treatment Outcome ; }, abstract = {PURPOSE: To compare the clinical outcomes and rotational stability after implantation of a toric intraocular lens (IOL) with textured haptics in eyes with normal vs high axial lengths (ALs).

SETTING: Nethradhama Superspeciality Eye Hospital, Bangalore, India.

DESIGN: 2-arm, retrospective comparative study.

METHODS: This retrospective study included 114 eyes of 114 patients who underwent femtolaser cataract surgery followed by implantation of the HOYA Vivinex Toric monofocal IOL (Model XY1A-SP), of which 62 and 52 eyes belonged to normal (≤23.9 mm) and high (≥24 mm) AL groups, respectively. 1 week and 3 months postoperatively, clinical outcomes and rotational stability of the toric IOL was evaluated.

RESULTS: 3 months postoperatively, % eyes achieving refractive astigmatism accuracy within ≤0.50 diopter, was 100% (n = 62) in the normal vs 94% (n = 49) in the high AL group. All eyes that is, 100% (n = 62) in the normal and 96.15% (n = 50) eyes in the high myopia group were <5 degrees of the intended axis. The mean change in postoperative rotation from 1 week to 3 months was 0.28 ± 0.09 degrees in the normal, and 0.30 ± 1.11 degrees in the high AL group (P = .80). No significant correlation was observed between AL and white-to-white diameter with 1-week postoperative rotation values. No eye required repositioning of toric IOL for significant misalignment.

CONCLUSIONS: No significant differences were observed for clinical outcomes and postoperative rotational stability between eyes with normal and high ALs, suggesting excellent rotational stability of the Vivinex Toric IOL with textured haptics in all eyes, irrespective of the preoperative AL measurements.}, } @article {pmid38376500, year = {2024}, author = {Krajewski, E and Lee, J and Olmstead, AJ and Simmons, Z}, title = {Comparison of Vowel and Sentence Intelligibility in People With Dysarthria Secondary to Amyotrophic Lateral Sclerosis.}, journal = {Journal of speech, language, and hearing research : JSLHR}, volume = {}, number = {}, pages = {1-10}, doi = {10.1044/2024_JSLHR-23-00497}, pmid = {38376500}, issn = {1558-9102}, abstract = {PURPOSE: In this study, we examined the utility of vowel intelligibility testing for assessing the impact of dysarthria on speech characteristics in people with amyotrophic lateral sclerosis (ALS). We tested the sensitivity and specificity of overall vowel identification, as well as that of vowel-specific identification, to dysarthria presence and severity. We additionally examined the relationship between vowel intelligibility and sentence intelligibility.

METHOD: Twenty-three people with ALS and 22 age- and sex-matched control speakers produced sentences from the Speech Intelligibility Test (SIT), as well as 10 American English monophthongs in /h/-vowel-/d/ words for the vowel intelligibility test (VIT). Data for SIT and VIT scores came from 135 listeners. Diagnostic accuracy of VIT measures was evaluated using the area under the curve of receiver operator characteristics. We then examined differences between control speakers, speakers with mild dysarthria, and speakers with severe dysarthria in their relationship between SIT and VIT scores.

RESULTS: The results suggest that the overall vowel intelligibility score showed high sensitivity and specificity in differentiating between speakers with and without dysarthria, even those with milder symptoms. In addition, single-vowel identification scores showed at least acceptable group differentiation between the mild and severe dysarthria groups, though fewer single vowels were acceptable discriminators between the control group and the group with mild dysarthria. Identification accuracy of /ɪ/ in particular showed excellent discrimination across all groups. Examination of the relationship between SIT and VIT scores suggests a severity-specific relationship. Speakers with SIT scores above 70% generally had higher SIT than VIT scores, whereas speakers with SIT below 70% generally had higher VIT than SIT scores.

DISCUSSION: Vowel intelligibility testing can detect speech impairments in speakers with mild dysarthria and residual articulatory function in speakers with severe dysarthria. Vowel intelligibility testing may, therefore, be a useful addition to intelligibility testing for individuals with dysarthria.}, } @article {pmid38376483, year = {2024}, author = {Lee, D and Jeong, HC and Kim, SY and Chung, JY and Cho, SH and Kim, KA and Cho, JH and Ko, BS and Cha, IJ and Chung, CG and Kim, ES and Lee, SB}, title = {A comparison study of pathological features and drug efficacy between Drosophila models of C9orf72 ALS/FTD.}, journal = {Molecules and cells}, volume = {47}, number = {1}, pages = {100005}, pmid = {38376483}, issn = {0219-1032}, mesh = {Animals ; Drosophila/genetics ; *Amyotrophic Lateral Sclerosis/genetics ; C9orf72 Protein/genetics ; *Frontotemporal Dementia ; *Neurodegenerative Diseases ; Levamisole/*analogs & derivatives ; }, abstract = {Amyotrophic lateral sclerosis is a devastating neurodegenerative disease with a complex genetic basis, presenting both in familial and sporadic forms. The hexanucleotide (G4C2) repeat expansion in the C9orf72 gene, which triggers distinct pathogenic mechanisms, has been identified as a major contributor to familial and sporadic Amyotrophic lateral sclerosis cases. Animal models have proven pivotal in understanding these mechanisms; however, discrepancies between models due to variable transgene sequence, expression levels, and toxicity profiles complicate the translation of findings. Herein, we provide a systematic comparison of 7 publicly available Drosophila transgenes modeling the G4C2 expansion under uniform conditions, evaluating variations in their toxicity profiles. Further, we tested 3 previously characterized disease-modifying drugs in selected lines to uncover discrepancies among the tested strains. Our study not only deepens our understanding of the C9orf72 G4C2 mutations but also presents a framework for comparing constructs with minute structural differences. This work may be used to inform experimental designs to better model disease mechanisms and help guide the development of targeted interventions for neurodegenerative diseases, thus bridging the gap between model-based research and therapeutic application.}, } @article {pmid38375749, year = {2024}, author = {Awassa, J and Soulé, S and Cornu, D and Ruby, C and El-Kirat-Chatel, S}, title = {Understanding the nanoscale adhesion forces between the fungal pathogen Candida albicans and antimicrobial zinc-based layered double hydroxides using single-cell and single-particle force spectroscopy.}, journal = {Nanoscale}, volume = {16}, number = {10}, pages = {5383-5394}, doi = {10.1039/d3nr06027f}, pmid = {38375749}, issn = {2040-3372}, mesh = {Humans ; *Candida albicans ; *Antifungal Agents/pharmacology ; Hydroxides/pharmacology/chemistry ; Zinc/pharmacology/chemistry ; Spectrum Analysis ; *Zinc Compounds ; }, abstract = {Antifungal resistance has become a very serious concern, and Candida albicans is considered one of the most opportunistic fungal pathogens responsible for several human infections. In this context, the use of new antifungal agents such as zinc-based layered double hydroxides to fight such fungal pathogens is considered one possible means to help limit the problem of antifungal resistance. In this study, we show that ZnAl LDH nanoparticles exhibit remarkable antifungal properties against C. albicans and cause serious cell wall damage, as revealed by growth tests and atomic force microscopy (AFM) imaging. To further link the antifungal activity of ZnAl LDHs to their adhesive behaviors toward C. albicans cells, AFM-based single-cell spectroscopy and single-particle force spectroscopy were used to probe the nanoscale adhesive interactions. The force spectroscopy analysis revealed that antimicrobial ZnAl LDHs exhibit specific surface interactions with C. albicans cells, demonstrating remarkable force magnitudes and adhesion frequencies in comparison with non-antifungal negative controls, e.g., Al-coated substrates and MgAl LDHs, which showed limited interactions with C. albicans cells. Force signatures suggest that such adhesive interactions may be attributed to the presence of agglutinin-like sequence (Als) adhesive proteins at the cell wall surface of C. albicans cells. Our findings propose the presence of a strong correlation between the antifungal effect provided by ZnAl LDHs and their nanoscale adhesive interactions with C. albicans cells at both the single-cell and single-particle levels. Therefore, ZnAl LDHs could interact with C. albicans fungal pathogens by specific adhesive interactions through which they adhere to fungal cells, leading to their damage and subsequent growth inhibition.}, } @article {pmid38374770, year = {2024}, author = {Pavey, N and Hannaford, A and van den Bos, M and Kiernan, MC and Menon, P and Vucic, S}, title = {Distinct neuronal circuits mediate cortical hyperexcitability in amyotrophic lateral sclerosis.}, journal = {Brain : a journal of neurology}, volume = {147}, number = {7}, pages = {2344-2356}, doi = {10.1093/brain/awae049}, pmid = {38374770}, issn = {1460-2156}, support = {//MND Research Australia/ ; 2001261//NHMRC/ ; 2010812//National Health & Medical Research Council/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology ; Male ; Female ; Middle Aged ; *Transcranial Magnetic Stimulation/methods ; *Motor Cortex/physiopathology ; Aged ; *Evoked Potentials, Motor/physiology ; Adult ; Nerve Net/physiopathology ; Neural Inhibition/physiology ; Electromyography ; }, abstract = {Cortical hyperexcitability is an important pathophysiological mechanism in amyotrophic lateral sclerosis (ALS), reflecting a complex interaction of inhibitory and facilitatory interneuronal processes that evolves in the degenerating brain. The advances in physiological techniques have made it possible to interrogate progressive changes in the motor cortex. Specifically, the direction of transcranial magnetic stimulation (TMS) stimulus within the primary motor cortex can be utilized to influence descending corticospinal volleys and to thereby provide information about distinct interneuronal circuits. Cortical motor function and cognition was assessed in 29 ALS patients with results compared to healthy volunteers. Cortical dysfunction was assessed using threshold-tracking TMS to explore alterations in short interval intracortical inhibition (SICI), short interval intracortical facilitation (SICF), the index of excitation and stimulus response curves using a figure-of-eight coil with the coil oriented relative to the primary motor cortex in a posterior-anterior, lateral-medial and anterior-posterior direction. Mean SICI, between interstimulus interval of 1-7 ms, was significantly reduced in ALS patients compared to healthy controls when assessed with the coil oriented in posterior-anterior (P = 0.044) and lateral-medial (P = 0.005) but not the anterior-posterior (P = 0.08) directions. A significant correlation between mean SICI oriented in a posterior-anterior direction and the total Edinburgh Cognitive and Behavioural ALS Screen score (Rho = 0.389, P = 0.037) was evident. In addition, the mean SICF, between interstimulus interval 1-5 ms, was significantly increased in ALS patients when recorded with TMS coil oriented in posterior-anterior (P = 0.035) and lateral-medial (P < 0.001) directions. In contrast, SICF recorded with TMS coil oriented in the anterior-posterior direction was comparable between ALS and controls (P = 0.482). The index of excitation was significantly increased in ALS patients when recorded with the TMS coil oriented in posterior-anterior (P = 0.041) and lateral-medial (P = 0.003) directions. In ALS patients, a significant increase in the stimulus response curve gradient was evident compared to controls when recorded with TMS coil oriented in posterior-anterior (P < 0.001), lateral-medial (P < 0.001) and anterior-posterior (P = 0.002) directions. The present study has established that dysfunction of distinct interneuronal circuits mediates the development of cortical hyperexcitability in ALS. Specifically, complex interplay between inhibitory circuits and facilitatory interneuronal populations, that are preferentially activated by stimulation in posterior-to-anterior or lateral-to-medial directions, promotes cortical hyperexcitability in ALS. Mechanisms that underlie dysfunction of these specific cortical neuronal circuits will enhance understanding of the pathophysiological processes in ALS, with the potential to uncover focussed therapeutic targets.}, } @article {pmid38374589, year = {2025}, author = {Mehdipour, A and Teshler, L and Dal Bello-Haas, V and Bouchard, V and Kuspinar, A}, title = {Translation of the Preference-Based Amyotrophic Lateral Sclerosis Scale into French.}, journal = {The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques}, volume = {52}, number = {1}, pages = {129-131}, doi = {10.1017/cjn.2024.18}, pmid = {38374589}, issn = {0317-1671}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/psychology/diagnosis ; Canada ; Male ; Female ; Translating ; Middle Aged ; Language ; Translations ; Surveys and Questionnaires ; Aged ; }, abstract = {The objective of this study was to translate the Preference-Based Amyotrophic Lateral Sclerosis Scale to French-Canadian. After the scale underwent forward and back translations, the expert committee examined the translated versions and found minor grammatical errors and suggested idioms to be changed to better represent French-Canadian language. Cognitive debriefing interviews were carried out to assess the pre-final version for clarity, and minor changes were made. Consensus from the expert committee and people with amyotrophic lateral sclerosis on the measure's clarity, word choice, and meaning were achieved, resulting in the final French version of the Preference-Based Amyotrophic Lateral Sclerosis Scale.}, } @article {pmid38374041, year = {2024}, author = {San Gil, R and Pascovici, D and Venturato, J and Brown-Wright, H and Mehta, P and Madrid San Martin, L and Wu, J and Luan, W and Chui, YK and Bademosi, AT and Swaminathan, S and Naidoo, S and Berning, BA and Wright, AL and Keating, SS and Curtis, MA and Faull, RLM and Lee, JD and Ngo, ST and Lee, A and Morsch, M and Chung, RS and Scotter, E and Lisowski, L and Mirzaei, M and Walker, AK}, title = {A transient protein folding response targets aggregation in the early phase of TDP-43-mediated neurodegeneration.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {1508}, pmid = {38374041}, issn = {2041-1723}, support = {1140386//Department of Health | National Health and Medical Research Council (NHMRC)/ ; }, mesh = {Animals ; Humans ; Mice ; *Amyotrophic Lateral Sclerosis/metabolism ; DNA-Binding Proteins/genetics/metabolism ; *Frontotemporal Dementia/metabolism ; *Frontotemporal Lobar Degeneration/metabolism ; Neurons/metabolism ; Proteomics ; *TDP-43 Proteinopathies/metabolism ; *Protein Aggregates ; }, abstract = {Understanding the mechanisms that drive TDP-43 pathology is integral to combating amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration (FTLD) and other neurodegenerative diseases. Here we generated a longitudinal quantitative proteomic map of the cortex from the cytoplasmic TDP-43 rNLS8 mouse model of ALS and FTLD, and developed a complementary open-access webtool, TDP-map (https://shiny.rcc.uq.edu.au/TDP-map/). We identified distinct protein subsets enriched for diverse biological pathways with temporal alterations in protein abundance, including increases in protein folding factors prior to disease onset. This included increased levels of DnaJ homolog subfamily B member 5, DNAJB5, which also co-localized with TDP-43 pathology in diseased human motor cortex. DNAJB5 over-expression decreased TDP-43 aggregation in cell and cortical neuron cultures, and knockout of Dnajb5 exacerbated motor impairments caused by AAV-mediated cytoplasmic TDP-43 expression in mice. Together, these findings reveal molecular mechanisms at distinct stages of ALS and FTLD progression and suggest that protein folding factors could be protective in neurodegenerative diseases.}, } @article {pmid38372843, year = {2024}, author = {Katerelos, A and Alexopoulos, P and Economou, P and Polychronopoulos, P and Chroni, E}, title = {Correction to: Cognitive function in amyotrophic lateral sclerosis: a cross‑sectional and prospective pragmatic clinical study with review of the literature.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {45}, number = {5}, pages = {2407}, doi = {10.1007/s10072-024-07408-9}, pmid = {38372843}, issn = {1590-3478}, } @article {pmid38372747, year = {2024}, author = {Yang, T and Li, C and Wei, Q and Pang, D and Cheng, Y and Huang, J and Lin, J and Xiao, Y and Jiang, Q and Wang, S and Shang, H}, title = {Genome-wide DNA methylation analysis related to ALS patient progression and survival.}, journal = {Journal of neurology}, volume = {271}, number = {5}, pages = {2672-2683}, pmid = {38372747}, issn = {1432-1459}, support = {82371430//National Natural Science Foundation of China/ ; 82101485//National Natural Science Foundation of China/ ; 2022ZDZX0023//Sichuan Science and Technology Program/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/mortality ; *DNA Methylation ; Male ; Female ; *Disease Progression ; Middle Aged ; Aged ; Epigenesis, Genetic ; Genome-Wide Association Study ; Follow-Up Studies ; }, abstract = {BACKGROUND: Epigenetics contributes to the pathogenesis of amyotrophic lateral sclerosis (ALS). We aimed to characterize the DNA methylation profiles associated with clinical heterogeneity in disease progression and survival among patients.

METHODS: We included a cohort of 41 patients with sporadic ALS, with a median follow-up of 86.9 months, and 27 rigorously matched healthy controls. Blood-based genome-wide DNA methylation analysis was conducted.

RESULTS: A total of 948 progression rate-associated differentially methylated positions, 298 progression rate-associated differentially methylated regions (R-DMRs), 590 survival time-associated DMPs, and 197 survival time-associated DMRs (S-DMRs) were identified, using complementary grouping strategies. Enrichment analysis of differentially methylated genes highlighted the involvement of synapses and axons in ALS progression and survival. Clinical analysis revealed a positive correlation between the average methylation levels of the R-DMR in PRDM8 and disease progression rate (r = 0.479, p = 0.002). Conversely, there was an inverse correlation between the average methylation levels of the R-DMR in ANKRD33 and disease progression rate (r = - 0.476, p = 0.002). In addition, patients with higher methylation levels within the S-DMR of ZNF696 experienced longer survival (p = 0.016), while those with elevated methylation levels in the S-DMR of RAI1 had shorter survival (p = 0.006).

CONCLUSION: DNA methylation holds promise as a potential biomarker for tracking disease progression and predicting survival outcome and also offers targets for precision medicine.}, } @article {pmid38372421, year = {2024}, author = {Miquel, E and Villarino, R and Martínez-Palma, L and Cassina, A and Cassina, P}, title = {Pyruvate dehydrogenase kinase 2 knockdown restores the ability of amyotrophic lateral sclerosis-linked SOD1G93A rat astrocytes to support motor neuron survival by increasing mitochondrial respiration.}, journal = {Glia}, volume = {72}, number = {5}, pages = {999-1011}, doi = {10.1002/glia.24516}, pmid = {38372421}, issn = {1098-1136}, support = {//Programa de Desarrollo de las Ciencias Básicas (PEDECIBA)/ ; FCE_1_2019_1_156461//Agencia Nacional de Investigación e Innovación/ ; }, mesh = {Animals ; Rats ; *Amyotrophic Lateral Sclerosis/genetics/metabolism ; *Astrocytes/metabolism ; Cells, Cultured ; Disease Models, Animal ; Motor Neurons/metabolism ; *Pyruvate Dehydrogenase Acetyl-Transferring Kinase/genetics/metabolism ; Respiration ; Superoxide Dismutase/genetics/metabolism ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is characterized by progressive motor neuron (MN) degeneration. Various studies using cellular and animal models of ALS indicate that there is a complex interplay between MN and neighboring non-neuronal cells, such as astrocytes, resulting in noncell autonomous neurodegeneration. Astrocytes in ALS exhibit a lower ability to support MN survival than nondisease-associated ones, which is strongly correlated with low-mitochondrial respiratory activity. Indeed, pharmacological inhibition of pyruvate dehydrogenase kinase (PDK) led to an increase in the mitochondrial oxidative phosphorylation pathway as the primary source of cell energy in SOD1G93A astrocytes and restored the survival of MN. Among the four PDK isoforms, PDK2 is ubiquitously expressed in astrocytes and presents low expression levels in neurons. Herein, we hypothesize whether selective knockdown of PDK2 in astrocytes may increase mitochondrial activity and, in turn, reduce SOD1G93A-associated toxicity. To assess this, cultured neonatal SOD1G93A rat astrocytes were incubated with specific PDK2 siRNA. This treatment resulted in a reduction of the enzyme expression with a concomitant decrease in the phosphorylation rate of the pyruvate dehydrogenase complex. In addition, PDK2-silenced SOD1G93A astrocytes exhibited restored mitochondrial bioenergetics parameters, adopting a more complex mitochondrial network. This treatment also decreased lipid droplet content in SOD1G93A astrocytes, suggesting a switch in energetic metabolism. Significantly, PDK2 knockdown increased the ability of SOD1G93A astrocytes to support MN survival, further supporting the major role of astrocyte mitochondrial respiratory activity in astrocyte-MN interactions. These results suggest that PDK2 silencing could be a cell-specific therapeutic tool to slow the progression of ALS.}, } @article {pmid38371486, year = {2024}, author = {Strang, P and Schultz, T and Ozanne, A}, title = {Partly unequal receipt of healthcare in last month of life in amyotrophic lateral sclerosis: a retrospective cohort study of the Stockholm region.}, journal = {Upsala journal of medical sciences}, volume = {129}, number = {}, pages = {}, pmid = {38371486}, issn = {2000-1967}, mesh = {Aged ; Female ; Humans ; Male ; *Amyotrophic Lateral Sclerosis/therapy ; Delivery of Health Care ; *Dementia/therapy ; *Frailty ; Palliative Care ; Retrospective Studies ; }, abstract = {CONTEXT: In amyotrophic lateral sclerosis (ALS), equal care is important, given that the disease often has complex symptoms at the end of life.

OBJECTIVES: The aim was to study the possible associations between demographic and clinical factors, including age, sex, and frailty, with acute healthcare utilization in the last month of life, measured by emergency room (ER) visits, admissions to acute hospitals and, acute hospitals as place of death, among patients with ALS. A second aim was to study whether receipt of specialized palliative care (SPC) affects above-mentioned healthcare utilization.

METHODS: Observational, retrospective study based on Region Stockholm's administrative data warehouse (VAL) in Sweden. Data were retrieved for 2015-2021 and analyzed with descriptive statistics and logistic regression models.

RESULTS: All deceased patients (n = 448) ≥18 years with ALS were included. The mean age was 70.5 years, 46% were women and 58% had risk of frailty according to Hospital Frailty Risk Score (HFRS). Ninety-nine (22%) were nursing home residents and 49% received SPC. The receipt of SPC in patients with ALS was equal in relation to gender, socio-economic standing, frailty, and age <75 years. Patients ≥75 years, those with dementia and/or residing in nursing homes (NH) were less likely to receive SPC (P = 0.01, P = 0.03 and P = 0.002, respectively). Receipt of SPC reduced ER visits (29% vs. 48%, P < 0.001) and deaths at hospital (12% vs. 48%, P <0.001). Patients who were frail, had a higher risk of ER visits and were more likely to die at an acute hospital setting (P < 0.001 and P = 0.004). NH residents were less likely to have ER visits and to die in hospital (P = 0.002 and P = 0.005).

CONCLUSIONS: The results indicate partly unequal distribution of palliative care, however the actual, individual preferences cannot be deducted from registry studies. All patients with ALS should be offered SPC when needed.

KEY MESSAGE: This register study shows that receipt of SPC in patients with ALS is equal in relation to gender, socioeconomic standing, frailty, and age <75 years, while those ≥75 years, with dementia, or residing in NH were somewhat less likely to receive SPC. Receipt of SPC reduces ER visits and acute hospital admissions.}, } @article {pmid38371336, year = {2024}, author = {Barnabe, A and Genestet, S and Gut-Gobert, C and Rivalain, C and Noury, JB and Goret, M and Barnier, A and De Moreuil, C and Espinasse, B and Le Mao, R and Leroyer, C and Couturaud, F and Tromeur, C}, title = {Venous thromboembolism and amyotrophic lateral sclerosis: the Venous Thrombo-Embolism and Sclerosis Lateral Amyotrophic study.}, journal = {Research and practice in thrombosis and haemostasis}, volume = {8}, number = {1}, pages = {102287}, pmid = {38371336}, issn = {2475-0379}, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a severe neurodegenerative disease. Given the inflammatory nature of ALS and the high number of ALS-related clinical circumstances (eg, prolonged immobilization and infections), patients with ALS may have a high risk of venous thromboembolism (VTE).

OBJECTIVES: To determine the annual incidence rate of VTE and the predictors of VTE in patients with ALS.

METHODS: We analyzed a prospective cohort of patients with ALS diagnosed between 2009 and 2019 followed in the Brest University Hospital ALS Centre.

RESULTS: Among 227 patients with ALS, VTE occurred in 19 patients during a median follow-up period of 717 days (IQR, 488-1308), yielding an annual incidence rate of 2.93% (95% CI, 1.88%-4.53%). Predictors for VTE were a family history of VTE (hazard ratio [HR], 15.24; 95% CI, 1.72-134.84; P = .01), the presence of noninvasive ventilation at ALS diagnosis (HR, 6.98; 95% CI, 1.09-44.59; P = .04) and a short time (ie, <213 days) between first symptoms and ALS diagnosis (HR, 5.48; 95% CI, 1.57-19.11; P = .01). Recurrent VTE occurred within 3 months after stopping anticoagulation in 5 patients (26.3%).

CONCLUSION: The annual incidence of VTE in patients with ALS is high. Predictive factors of VTE were a VTE history, noninvasive ventilation, and a short time between first symptoms of ALS and ALS diagnosis.}, } @article {pmid38370434, year = {2024}, author = {Chen, C and Qi, J and Li, Y and Li, D and Wu, L and Li, R and Chen, Q and Sun, N}, title = {Applications of Raman spectroscopy in the diagnosis and monitoring of neurodegenerative diseases.}, journal = {Frontiers in neuroscience}, volume = {18}, number = {}, pages = {1301107}, pmid = {38370434}, issn = {1662-4548}, abstract = {Raman scattering is an inelastic light scattering that occurs in a manner reflective of the molecular vibrations of molecular structures and chemical conditions in a given sample of interest. Energy changes in the scattered light can be assessed to determine the vibration mode and associated molecular and chemical conditions within the sample, providing a molecular fingerprint suitable for sample identification and characterization. Raman spectroscopy represents a particularly promising approach to the molecular analysis of many diseases owing to clinical advantages including its instantaneous nature and associated high degree of stability, as well as its ability to yield signal outputs corresponding to a single molecule type without any interference from other molecules as a result of its narrow peak width. This technology is thus ideally suited to the simultaneous assessment of multiple analytes. Neurodegenerative diseases represent an increasingly significant threat to global public health owing to progressive population aging, imposing a severe physical and social burden on affected patients who tend to develop cognitive and/or motor deficits beginning between the ages of 50 and 70. Owing to a relatively limited understanding of the etiological basis for these diseases, treatments are lacking for the most common neurodegenerative diseases, which include Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. The present review was formulated with the goal of briefly explaining the principle of Raman spectroscopy and discussing its potential applications in the diagnosis and evaluation of neurodegenerative diseases, with a particular emphasis on the research prospects of this novel technological platform.}, } @article {pmid38369520, year = {2024}, author = {Adashek, JJ and Pandya, C and Maragakis, NJ and De, P and Cohen, PR and Kato, S and Kurzrock, R}, title = {Neuregulin-1 and ALS19 (ERBB4): at the crossroads of amyotrophic lateral sclerosis and cancer.}, journal = {BMC medicine}, volume = {22}, number = {1}, pages = {74}, pmid = {38369520}, issn = {1741-7015}, support = {U10 CA180888/CA/NCI NIH HHS/United States ; UG1 CA233198/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics ; *Neoplasms/genetics ; *Neuregulin-1/genetics/metabolism ; *Receptor, ErbB-4/genetics/metabolism ; Signal Transduction ; }, abstract = {BACKGROUND: Neuregulin-1 (NRG1) is implicated in both cancer and neurologic diseases such as amyotrophic lateral sclerosis (ALS); however, to date, there has been little cross-field discussion between neurology and oncology in regard to these genes and their functions.

MAIN BODY: Approximately 0.15-0.5% of cancers harbor NRG1 fusions that upregulate NRG1 activity and hence that of the cognate ERBB3/ERBB4 (HER3/HER4) receptors; abrogating this activity with small molecule inhibitors/antibodies shows preliminary tissue-agnostic anti-cancer activity. Notably, ERBB/HER pharmacologic suppression is devoid of neurologic toxicity. Even so, in ALS, attenuated ERBB4/HER4 receptor activity (due to loss-of-function germline mutations or other mechanisms in sporadic disease) is implicated; indeed, ERBB4/HER4 is designated ALS19. Further, secreted-type NRG1 isoforms may be upregulated (perhaps via a feedback loop) and could contribute to ALS pathogenesis through aberrant glial cell stimulation via enhanced activity of other (e.g., ERBB1-3/HER1-3) receptors and downstream pathways. Hence, pan-ERBB inhibitors, already in use for cancer, may be agents worthy of testing in ALS.

CONCLUSION: Common signaling cascades between cancer and ALS may represent novel therapeutic targets for both diseases.}, } @article {pmid38368936, year = {2024}, author = {Herman, M and Randall, GW and Spiegel, JL and Maldonado, DJ and Simoes, S}, title = {Endo-lysosomal dysfunction in neurodegenerative diseases: opinion on current progress and future direction in the use of exosomes as biomarkers.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {379}, number = {1899}, pages = {20220387}, pmid = {38368936}, issn = {1471-2970}, support = {R01 AG071868/AG/NIA NIH HHS/United States ; R21 AG070768/AG/NIA NIH HHS/United States ; }, mesh = {Humans ; *Neurodegenerative Diseases/diagnosis/metabolism ; *Exosomes ; *Alzheimer Disease/diagnosis ; Lysosomes/metabolism ; Biomarkers/metabolism ; }, abstract = {Over the past two decades, increased research has highlighted the connection between endosomal trafficking defects and neurodegeneration. The endo-lysosomal network is an important, complex cellular system specialized in the transport of proteins, lipids, and other metabolites, essential for cell homeostasis. Disruption of this pathway is linked to a wide range of neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease and frontotemporal dementia. Furthermore, there is strong evidence that defects in this pathway create opportunities for diagnostic and therapeutic intervention. In this Opinion piece, we concisely address the role of endo-lysosomal dysfunction in five neurodegenerative diseases and discuss how future research can investigate this intracellular pathway, including extracellular vesicles with a specific focus on exosomes for the identification of novel disease biomarkers. This article is part of a discussion meeting issue 'Understanding the endo-lysosomal network in neurodegeneration'.}, } @article {pmid38367882, year = {2024}, author = {Godoy-Corchuelo, JM and Ali, Z and Brito Armas, JM and Martins-Bach, AB and García-Toledo, I and Fernández-Beltrán, LC and López-Carbonero, JI and Bascuñana, P and Spring, S and Jimenez-Coca, I and Muñoz de Bustillo Alfaro, RA and Sánchez-Barrena, MJ and Nair, RR and Nieman, BJ and Lerch, JP and Miller, KL and Ozdinler, HP and Fisher, EMC and Cunningham, TJ and Acevedo-Arozena, A and Corrochano, S}, title = {TDP-43-M323K causes abnormal brain development and progressive cognitive and motor deficits associated with mislocalised and increased levels of TDP-43.}, journal = {Neurobiology of disease}, volume = {193}, number = {}, pages = {106437}, pmid = {38367882}, issn = {1095-953X}, support = {MC_EX_MR/N501931/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Animals ; Child, Preschool ; Humans ; Mice ; *Amyotrophic Lateral Sclerosis/metabolism ; Brain/metabolism ; Cognition ; DNA-Binding Proteins/genetics/metabolism ; *Frontotemporal Dementia/genetics/pathology ; *TDP-43 Proteinopathies/genetics/pathology ; }, abstract = {TDP-43 pathology is found in several neurodegenerative disorders, collectively referred to as "TDP-43 proteinopathies". Aggregates of TDP-43 are present in the brains and spinal cords of >97% of amyotrophic lateral sclerosis (ALS), and in brains of ∼50% of frontotemporal dementia (FTD) patients. While mutations in the TDP-43 gene (TARDBP) are usually associated with ALS, many clinical reports have linked these mutations to cognitive impairments and/or FTD, but also to other neurodegenerative disorders including Parkinsonism (PD) or progressive supranuclear palsy (PSP). TDP-43 is a ubiquitously expressed, highly conserved RNA-binding protein that is involved in many cellular processes, mainly RNA metabolism. To investigate systemic pathological mechanisms in TDP-43 proteinopathies, aiming to capture the pleiotropic effects of TDP-43 mutations, we have further characterised a mouse model carrying a point mutation (M323K) within the endogenous Tardbp gene. Homozygous mutant mice developed cognitive and behavioural deficits as early as 3 months of age. This was coupled with significant brain structural abnormalities, mainly in the cortex, hippocampus, and white matter fibres, together with progressive cortical interneuron degeneration and neuroinflammation. At the motor level, progressive phenotypes appeared around 6 months of age. Thus, cognitive phenotypes appeared to be of a developmental origin with a mild associated progressive neurodegeneration, while the motor and neuromuscular phenotypes seemed neurodegenerative, underlined by a progressive loss of upper and lower motor neurons as well as distal denervation. This is accompanied by progressive elevated TDP-43 protein and mRNA levels in cortex and spinal cord of homozygous mutant mice from 3 months of age, together with increased cytoplasmic TDP-43 mislocalisation in cortex, hippocampus, hypothalamus, and spinal cord at 12 months of age. In conclusion, we find that Tardbp M323K homozygous mutant mice model many aspects of human TDP-43 proteinopathies, evidencing a dual role for TDP-43 in brain morphogenesis as well as in the maintenance of the motor system, making them an ideal in vivo model system to study the complex biology of TDP-43.}, } @article {pmid38367748, year = {2024}, author = {La Cognata, V and Morello, G and Guarnaccia, M and Cavallaro, S}, title = {The multifaceted role of the CXC chemokines and receptors signaling axes in ALS pathophysiology.}, journal = {Progress in neurobiology}, volume = {235}, number = {}, pages = {102587}, doi = {10.1016/j.pneurobio.2024.102587}, pmid = {38367748}, issn = {1873-5118}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis ; Signal Transduction ; Motor Neurons ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a late-onset motor neuron disease with complex genetic basis and still no clear etiology. Multiple intertwined layers of immune system-related dysfunctions and neuroinflammatory mechanisms are emerging as substantial determinants in ALS onset and progression. In this review, we collect the increasingly arising evidence implicating four main CXC chemokines/cognate receptors signaling axes (CXCR1/2-CXCL1/2/8; CXCR3-CXCL9/10/11; CXCR4/7-CXCL12; CXCR5-CXCL13) in the pathophysiology of ALS. Findings in preclinical models implicate these signaling pathways in motor neuron toxicity and neuroprotection, while in ALS patients dysregulation of CXCLs/CXCRs has been shown at both central and peripheral levels. Immunological monitoring of CXC-ligands in ALS may allow tracking of disease progression, while pharmacological modulation of CXC-receptors provides a novel therapeutic strategy. A deeper understanding of the interplay between CXC-mediated neuroinflammation and ALS is crucial to advance research into treatments for this debilitating uncurable disorder.}, } @article {pmid38367681, year = {2024}, author = {Arsuffi-Marcon, R and Souza, LG and Santos-Miranda, A and Joviano-Santos, JV}, title = {Neurotoxicity of Pyrethroids in neurodegenerative diseases: From animals' models to humans' studies.}, journal = {Chemico-biological interactions}, volume = {391}, number = {}, pages = {110911}, doi = {10.1016/j.cbi.2024.110911}, pmid = {38367681}, issn = {1872-7786}, mesh = {Animals ; Humans ; *Pyrethrins/toxicity ; *Insecticides/toxicity ; *Neurodegenerative Diseases/chemically induced ; *Neurotoxicity Syndromes ; *Pesticides/toxicity ; Mammals ; }, abstract = {Neurodegenerative diseases are associated with diverse symptoms, both motor and mental. Genetic and environmental factors can trigger neurodegenerative diseases. Chemicals as pesticides are constantly used in agriculture and also domestically. In this regard, pyrethroids (PY), are a class of insecticides in which its main mechanism of action is through disruption of voltage-dependent sodium channels function in insects. However, in mammals, they can also induce oxidative stress and enzyme dysfunction. This review investigates the association between PY and neurodegenerative diseases as Alzheimer's, Huntington's, Parkinson's, Amyotrophic Lateral Sclerosis, and Autism in animal models and humans. Published works using specific and non-specific models for these diseases were selected. We showed a tendency toward the development and/or aggravating of these neurodegenerative diseases following exposure to PYs. In animal models, the biochemical mechanisms of the diseases and their interaction with the insecticides are more deeply investigated. Nonetheless, only a few studies considered the specific model for each type of disease to analyze the impacts of the exposure. The choice of a specific model during the research is an important step and our review highlights the knowledge gaps of PYs effects using these models reinforcing the importance of them during the design of the experiments.}, } @article {pmid38367047, year = {2024}, author = {Sun, W and Liu, SH and Wei, XJ and Sun, H and Ma, ZW and Yu, XF}, title = {Potential of neuroimaging as a biomarker in amyotrophic lateral sclerosis: from structure to metabolism.}, journal = {Journal of neurology}, volume = {271}, number = {5}, pages = {2238-2257}, pmid = {38367047}, issn = {1432-1459}, support = {No. JLSWSRCZX2023-13//the Medical and Health Talents Special Foundation of Jilin Province/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/diagnostic imaging/metabolism ; Humans ; *Neuroimaging/methods/standards ; *Biomarkers/metabolism ; Brain/diagnostic imaging/metabolism ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by motor neuron degeneration. The development of ALS involves metabolite alterations leading to tissue lesions in the nervous system. Recent advances in neuroimaging have significantly improved our understanding of the underlying pathophysiology of ALS, with findings supporting the corticoefferent axonal disease progression theory. Current studies on neuroimaging in ALS have demonstrated inconsistencies, which may be due to small sample sizes, insufficient statistical power, overinterpretation of findings, and the inherent heterogeneity of ALS. Deriving meaningful conclusions solely from individual imaging metrics in ALS studies remains challenging, and integrating multimodal imaging techniques shows promise for detecting valuable ALS biomarkers. In addition to giving an overview of the principles and techniques of different neuroimaging modalities, this review describes the potential of neuroimaging biomarkers in the diagnosis and prognostication of ALS. We provide an insight into the underlying pathology, highlighting the need for standardized protocols and multicenter collaborations to advance ALS research.}, } @article {pmid38366598, year = {2024}, author = {Ke, YD and van Hummel, A and Au, C and Chan, G and Lee, WS and van der Hoven, J and Przybyla, M and Deng, Y and Sabale, M and Morey, N and Bertz, J and Feiten, A and Ippati, S and Stevens, CH and Yang, S and Gladbach, A and Haass, NK and Kril, JJ and Blair, IP and Delerue, F and Ittner, LM}, title = {Targeting 14-3-3θ-mediated TDP-43 pathology in amyotrophic lateral sclerosis and frontotemporal dementia mice.}, journal = {Neuron}, volume = {112}, number = {8}, pages = {1249-1264.e8}, doi = {10.1016/j.neuron.2024.01.022}, pmid = {38366598}, issn = {1097-4199}, mesh = {Animals ; Mice ; *Amyotrophic Lateral Sclerosis/metabolism ; DNA-Binding Proteins/genetics/metabolism ; *Frontotemporal Dementia/metabolism ; Neurons/metabolism ; }, abstract = {Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are characterized by cytoplasmic deposition of the nuclear TAR-binding protein 43 (TDP-43). Although cytoplasmic re-localization of TDP-43 is a key event in the pathogenesis of ALS/FTD, the underlying mechanisms remain unknown. Here, we identified a non-canonical interaction between 14-3-3θ and TDP-43, which regulates nuclear-cytoplasmic shuttling. Neuronal 14-3-3θ levels were increased in sporadic ALS and FTD with TDP-43 pathology. Pathogenic TDP-43 showed increased interaction with 14-3-3θ, resulting in cytoplasmic accumulation, insolubility, phosphorylation, and fragmentation of TDP-43, resembling pathological changes in disease. Harnessing this increased affinity of 14-3-3θ for pathogenic TDP-43, we devised a gene therapy vector targeting TDP-43 pathology, which mitigated functional deficits and neurodegeneration in different ALS/FTD mouse models expressing mutant or non-mutant TDP-43, including when already symptomatic at the time of treatment. Our study identified 14-3-3θ as a mediator of cytoplasmic TDP-43 localization with implications for ALS/FTD pathogenesis and therapy.}, } @article {pmid38364912, year = {2024}, author = {Du, L and Roy, S and Wang, P and Li, Z and Qiu, X and Zhang, Y and Yuan, J and Guo, B}, title = {Unveiling the future: Advancements in MRI imaging for neurodegenerative disorders.}, journal = {Ageing research reviews}, volume = {95}, number = {}, pages = {102230}, doi = {10.1016/j.arr.2024.102230}, pmid = {38364912}, issn = {1872-9649}, mesh = {Humans ; *Diffusion Tensor Imaging/methods ; Artificial Intelligence ; Brain/pathology ; Magnetic Resonance Imaging/methods ; *Neurodegenerative Diseases/pathology ; }, abstract = {Neurodegenerative disorders represent a significant and growing global health challenge, necessitating continuous advancements in diagnostic tools for accurate and early detection. This work explores the recent progress in Magnetic Resonance Imaging (MRI) techniques and their application in the realm of neurodegenerative disorders. The introductory section provides a comprehensive overview of the study's background, significance, and objectives. Recognizing the current challenges associated with conventional MRI, the manuscript delves into advanced imaging techniques such as high-resolution structural imaging (HR-MRI), functional MRI (fMRI), diffusion tensor imaging (DTI), and positron emission tomography-MRI (PET-MRI) fusion. Each technique is critically examined regarding its potential to address theranostic limitations and contribute to a more nuanced understanding of the underlying pathology. A substantial portion of the work is dedicated to exploring the applications of advanced MRI in specific neurodegenerative disorders, including Parkinson's disease, Alzheimer's disease, Huntington's disease, and Amyotrophic Lateral Sclerosis (ALS). In addressing the future landscape, the manuscript examines technological advances, including the integration of machine learning and artificial intelligence in neuroimaging. The conclusion summarizes key findings, outlines implications for future research, and underscores the importance of these advancements in reshaping our understanding and approach to neurodegenerative disorders.}, } @article {pmid38363426, year = {2024}, author = {Tziortzouda, P and Steyaert, J and Scheveneels, W and Sicart, A and Stoklund Dittlau, K and Barbosa Correia, AM and Burg, T and Pal, A and Hermann, A and Van Damme, P and Moens, TG and Van Den Bosch, L}, title = {PP2A and GSK3 act as modifiers of FUS-ALS by modulating mitochondrial transport.}, journal = {Acta neuropathologica}, volume = {147}, number = {1}, pages = {41}, pmid = {38363426}, issn = {1432-0533}, support = {P40 OD018537/OD/NIH HHS/United States ; }, mesh = {Animals ; Humans ; Mice ; *Amyotrophic Lateral Sclerosis/pathology ; Glycogen Synthase Kinase 3/genetics/metabolism ; Protein Phosphatase 2/genetics/metabolism ; RNA-Binding Protein FUS/genetics/metabolism ; *Neurodegenerative Diseases/pathology ; Kinesins/genetics/metabolism ; Motor Neurons/metabolism ; Drosophila/genetics/metabolism ; Mutation/genetics ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease which currently lacks effective treatments. Mutations in the RNA-binding protein FUS are a common cause of familial ALS, accounting for around 4% of the cases. Understanding the mechanisms by which mutant FUS becomes toxic to neurons can provide insight into the pathogenesis of both familial and sporadic ALS. We have previously observed that overexpression of wild-type or ALS-mutant FUS in Drosophila motor neurons is toxic, which allowed us to screen for novel genetic modifiers of the disease. Using a genome-wide screening approach, we identified Protein Phosphatase 2A (PP2A) and Glycogen Synthase Kinase 3 (GSK3) as novel modifiers of FUS-ALS. Loss of function or pharmacological inhibition of either protein rescued FUS-associated lethality in Drosophila. Consistent with a conserved role in disease pathogenesis, pharmacological inhibition of both proteins rescued disease-relevant phenotypes, including mitochondrial trafficking defects and neuromuscular junction failure, in patient iPSC-derived spinal motor neurons (iPSC-sMNs). In FUS-ALS flies, mice, and human iPSC-sMNs, we observed reduced GSK3 inhibitory phosphorylation, suggesting that FUS dysfunction results in GSK3 hyperactivity. Furthermore, we found that PP2A acts upstream of GSK3, affecting its inhibitory phosphorylation. GSK3 has previously been linked to kinesin-1 hyperphosphorylation. We observed this in both flies and iPSC-sMNs, and we rescued this hyperphosphorylation by inhibiting GSK3 or PP2A. Moreover, increasing the level of kinesin-1 expression in our Drosophila model strongly rescued toxicity, confirming the relevance of kinesin-1 hyperphosphorylation. Our data provide in vivo evidence that PP2A and GSK3 are disease modifiers, and reveal an unexplored mechanistic link between PP2A, GSK3, and kinesin-1, that may be central to the pathogenesis of FUS-ALS and sporadic forms of the disease.}, } @article {pmid38362496, year = {2024}, author = {Hoyer, LL and Freeman, BA and Hogan, EK and Hernandez, AG}, title = {Use of a Candida albicans SC5314 PacBio HiFi reads dataset to close gaps in the reference genome assembly, reveal a subtelomeric gene family, and produce accurate phased allelic sequences.}, journal = {Frontiers in cellular and infection microbiology}, volume = {14}, number = {}, pages = {1329438}, pmid = {38362496}, issn = {2235-2988}, support = {R15 DE026401/DE/NIDCR NIH HHS/United States ; }, mesh = {*Candida albicans/genetics ; *Genome, Fungal ; Base Sequence ; Repetitive Sequences, Nucleic Acid ; Telomere/genetics ; Sequence Analysis, DNA/methods ; High-Throughput Nucleotide Sequencing ; }, abstract = {Candida albicans SC5314 is the most-often used strain for molecular manipulation of the species. The SC5314 reference genome sequence is the result of considerable effort from many scientists and has advanced research into fungal biology and pathogenesis. Although the resource is highly developed and presented in a phased diploid format, the sequence includes gaps and does not extend to the telomeres on its eight chromosome pairs. Accurate SC5314 genome assembly is complicated by the presence of extensive repeated sequences and considerable allelic length variation at some loci. Advances in genome sequencing technology provide the tools to obtain highly accurate long-read data that span even the most-difficult-to-assemble genome regions. Here, we describe derivation of a PacBio HiFi data set and creation of a collapsed haploid telomere-to-telomere assembly of the SC5314 genome (ASM3268872v1) that revealed previously unknown features of the strain. ASM3268872v1 subtelomeric distances were up to 19 kb larger than in the reference genome and revealed a family of highly conserved DNA helicase-encoding genes at 10 of the 16 chromosome ends. We also describe alignments of individual HiFi reads to deduce accurate diploid sequences for the most notoriously difficult-to-assemble C. albicans genes: the agglutinin-like sequence (ALS) gene family. We provide a tutorial that demonstrates how the HiFi reads can be visualized to explore any region of interest. Availability of the HiFi reads data set and the ASM3268872v1 comparative guide assembly will streamline research efforts because accurate diploid sequences can be derived using simple in silico methods rather than time-consuming laboratory-bench approaches.}, } @article {pmid38360060, year = {2024}, author = {El-Ghazouly, DE and Yassien, RI}, title = {Bisphosphonate's effect on the tongue in adult male albino rats and the possible protective role of rutin: light and scanning electron microscopic study.}, journal = {Anatomy & cell biology}, volume = {57}, number = {1}, pages = {129-142}, pmid = {38360060}, issn = {2093-3665}, abstract = {Alendronate sodium (ALS) is a nitrogen-containing bisphosphonate used for the treatment of different bone disorders. However, its adverse effect on oral soft tissue has been detected. Rutin (RUT) is natural flavonoid with antioxidant and anti-inflammatory properties. This work aimed to investigate the possible effect of ALS on the tongue of adult male albino rats and to evaluate the possible protective role of RUT. Forty adult male albino rats were equally divided into four groups: group I (control), group II (RUT): Received RUT 50 mg/kg, group III (ALS): Received ALS 1 mg/kg, group IV (ALS+RUT): Received ALS and RUT with the same doses as pervious groups. The drugs were given once daily for 5 weeks. Tongue specimens were taken and processed for light and scanning electron microscopic inspection. ALS treated group revealed structural changes in the tongue in the form of decrease in the height of the filiform papillae with blunt ends, marked atrophy in some papillae with areas of focal loss, loss of some epithelial cells, pyknotic nuclei and cytoplasmic vacuoles in some epithelial cells. The lamina propria showed inflammatory cellular infiltration with congested blood vessels. Statistically, there were highly significant decrease in the number of proliferating cell nuclear antigen immunopositive cells, area percentage of Bcl-2 immunoexpression and highly significant increase in the collagen content compared to control group. Administration of RUT with ALS minimizes these changes. RUT protected the rat tongue against the histological and immunohistochemical changes induced by ALS through its antioxidant and anti-inflammatory properties.}, } @article {pmid38359044, year = {2024}, author = {Vieira, FG and Tassinari, VR and Kidd, JD and Moreno, A and Thompson, K and Perrin, S and Gill, A and Hatzipetros, T}, title = {PERK modulation, with GSK2606414, Sephin1 or salubrinal, failed to produce therapeutic benefits in the SOD1G93A mouse model of ALS.}, journal = {PloS one}, volume = {19}, number = {2}, pages = {e0292190}, pmid = {38359044}, issn = {1932-6203}, mesh = {Mice ; Humans ; Animals ; *Guanabenz/pharmacology/therapeutic use/*analogs & derivatives ; eIF-2 Kinase/genetics/metabolism ; *Amyotrophic Lateral Sclerosis/drug therapy/genetics ; Clonidine ; Unfolded Protein Response ; Adrenergic alpha-2 Receptor Agonists ; Adenine/*analogs & derivatives ; *Cinnamates ; *Indoles ; Thiourea/*analogs & derivatives ; }, abstract = {Amyotrophic lateral sclerosis (ALS) has been linked to overactivity of the protein kinase RNA-like ER kinase (PERK) branch of the unfolded protein response (UPR) pathway, both in ALS patients and mouse models. However, attempts to pharmacologically modulate PERK for therapeutic benefit have yielded inconsistent and often conflicting results. This study sought to address these discrepancies by comprehensively evaluating three commonly used, CNS-penetrant, PERK modulators (GSK2606414, salubrinal, and Sephin1) in the same experimental models, with the goal of assessing the viability of targeting the PERK pathway as a therapeutic strategy for ALS. To achieve this goal, a tunicamycin-challenge assay was developed using wild-type mice to monitor changes in liver UPR gene expression in response to PERK pathway modulation. Subsequently, multiple dosing regimens of each PERK modulator were tested in standardized, well-powered, gender-matched, and litter-matched survival efficacy studies using the SOD1G93A mouse model of ALS. The alpha-2-adrenergic receptor agonist clonidine was also tested to elucidate the results obtained from the Sephin1, and of the previously reported guanabenz studies, by comparing the effects of presence or absence of α-2 agonism. The results revealed that targeting PERK may not be an ideal approach for ALS treatment. Inhibiting PERK with GSK2606414 or activating it with salubrinal did not confer therapeutic benefits. While Sephin1 showed some promising therapeutic effects, it appears that these outcomes were mediated through PERK-independent mechanisms. Clonidine also produced some favorable therapeutic effects, which were unexpected and not linked to the UPR. In conclusion, this study highlights the challenges of pharmacologically targeting PERK for therapeutic purposes in the SOD1G93A mouse model and suggests that exploring other targets within, and outside, the UPR may be more promising avenues for ALS treatment.}, } @article {pmid38358553, year = {2024}, author = {Brakemeier, S and Lipka, J and Schlag, M and Kleinschnitz, C and Hagenacker, T}, title = {Risdiplam improves subjective swallowing quality in non-ambulatory adult patients with 5q-spinal muscular atrophy despite advanced motor impairment.}, journal = {Journal of neurology}, volume = {271}, number = {5}, pages = {2649-2657}, pmid = {38358553}, issn = {1432-1459}, mesh = {Humans ; Male ; Female ; Middle Aged ; Adult ; *Deglutition Disorders/etiology/physiopathology/drug therapy ; Pyrimidines/therapeutic use/pharmacology ; Aged ; Spinal Muscular Atrophies of Childhood/drug therapy/physiopathology/complications ; Treatment Outcome ; Deglutition/physiology/drug effects ; Prospective Studies ; Muscular Atrophy, Spinal/drug therapy/physiopathology ; Young Adult ; *Azo Compounds ; }, abstract = {BACKGROUND: 5q-associated spinal muscular atrophy (SMA) is characterized by the progressive loss of motor neurons with consecutive weakness and atrophy of the limb, respiratory, and bulbar muscles. While trunk and limb motor function improve or stabilize in adults with SMA under nusinersen and risdiplam treatment, the efficacy on bulbar function in this age group of patients remains uncertain. However, it is important to assess bulbar dysfunction, which frequently occurs in the disease course and is associated with increased morbidity and mortality.

METHODS: Bulbar function was evaluated prospectively in 25 non-ambulatory adults with type 2 and 3 SMA before and 4 and 12 months after risdiplam treatment initiation using the Sydney Swallow Questionnaire (SSQ) and the bulbar subscore of the Amyotrophic Lateral Sclerosis Functional Rating Scale Revised (b-ALSFRS-R). Extremity function was assessed using the Hammersmith Functional Motor Scale Expanded (HFMSE) and Revised Upper Limb Module (RULM).

RESULTS: Subjective swallowing quality, measured with the SSQ, improved after 12 months of therapy with risdiplam. For the b-ALSFRS-R, a non-significant trend towards improvement was observed. The RULM score improved after 12 months of risdiplam therapy, but not the HFMSE score. HFMSE and RULM scores did not correlate with the SSQ but the b-ALSFRS-R score at baseline.

CONCLUSIONS: The improvement in subjective swallowing quality under risdiplam treatment, despite an advanced disease stage with severe motor deficits, strengthens the importance of a standardized bulbar assessment in addition to established motor scores. This may reveal relevant treatment effects and help individualize treatment decisions in the future.}, } @article {pmid38358049, year = {2024}, author = {Milani, A and Panozzo, S and Grazia, TM and Scarabel, L}, title = {Development of a rapid detection assay for acetolactate synthase inhibitors resistance in three Amaranthus weed species through loop-mediated isothermal amplification.}, journal = {Journal of the science of food and agriculture}, volume = {104}, number = {9}, pages = {5522-5532}, doi = {10.1002/jsfa.13385}, pmid = {38358049}, issn = {1097-0010}, support = {//Regione Emilia-Romagna/ ; }, mesh = {*Amaranthus/genetics/drug effects ; *Acetolactate Synthase/genetics/metabolism/antagonists & inhibitors ; *Nucleic Acid Amplification Techniques/methods ; *Herbicide Resistance/genetics ; *Plant Weeds/drug effects/genetics ; *Plant Proteins/genetics/metabolism ; *Herbicides/pharmacology ; Enzyme Inhibitors/pharmacology ; Molecular Diagnostic Techniques ; }, abstract = {BACKGROUND: The early detection of herbicide resistance in weeds is a key factor to avoid herbicide waste and improve agriculture sustainability. The present study aimed to develop and validate an allele-specific loop-mediated isothermal amplification (AS-LAMP) assay for the quick on-site detection of the resistance-endowing point mutation Trp-574-Leu in the acetolactate synthase (ALS) gene in three widely diffused Amaranthus weed species: Amaranthus retroflexus, Amaranthus hybridus and Amaranthus tuberculatus.

RESULTS: The AS-LAMP protocol was developed on wild-type and ALS-mutant plants of the three species and revealed that the amplification approach with only the primer set specific for the mutant allele (574-Leu) was the most promising. The validation and estimation of the AS-LAMP performance evaluated by comparing the results with those of the molecular marker (cleaved amplified polymorphic sequences) indicated that, although the sensitivity and specificity were relatively high in all species (overall 100 and > 65%, respectively), precision was high for A. hybridus L. and A. retroflexus L. (75 and 79%, respectively), but quite low for A. tuberculatus (Moq.) J. D. Sauer (59%). The LAMP assay was also effective on crude genomic DNA extraction, allowing the quick detection of mutant plants in field situation (on site resistance detection).

CONCLUSION: The proposed AS-LAMP method has proven to be a promising technique for rapid detection of resistance as a result of Trp-574-Leu on the two monoecious weedy Amaranthus species but resulted less effective in the genetically variable dioecious species A. tuberculatus. © 2024 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.}, } @article {pmid38357638, year = {2024}, author = {Gerritzen, EV and Lee, AR and McDermott, O and Coulson, N and Orrell, M}, title = {Online peer support for people with Amyotrophic Lateral Sclerosis (ALS): a narrative synthesis systematic review.}, journal = {Frontiers in digital health}, volume = {6}, number = {}, pages = {1138530}, pmid = {38357638}, issn = {2673-253X}, abstract = {BACKGROUND: Amyotrophic Lateral Sclerosis (ALS) significantly impacts the lives of people with the diagnosis and their families. A supportive social environment is important for people with ALS to adopt effective coping strategies and health behaviours, and reduce depressive symptoms. Peer support can provide a supportive social environment and can happen in-person and online. Advantages of online peer support are that people can engage from their own home, at their own time and pace, and that it offers a variety of different platforms and modes of communication.

OBJECTIVES: To (1) explore the benefits and challenges of online peer support for people with ALS, and (2) identify successful elements of online peer support for people with ALS.

METHODS: The method selected for this systematic review was a narrative synthesis. Six databases were systematically searched in April 2020 for articles published between 1989 and 2020. The search was updated in June 2022. The quality of the included studies was assessed with the Critical Appraisal Skills Programme qualitative research checklist.

RESULTS: 10,987 unique articles were identified through the systematic database search. Of those, 9 were included in this review. One of the main benefits of online peer support was that people could communicate using text rather than needing verbal communication, which can be challenging for some with ALS. Successful elements included using profile pages and graphics to identify others with similar or relevant experiences. Challenges included ALS symptoms which could make it difficult to use technological devices.

CONCLUSIONS: Peer support can provide a non-judgmental and supportive environment for people with ALS, in which they can exchange experiences and emotional support, which can help people in developing adaptive coping strategies. However, ALS symptoms may make it more difficult for people to use technological devices and engage in online peer support. More research is needed to identify what kind of specific barriers people with ALS experience, and how these could be overcome.}, } @article {pmid38356886, year = {2024}, author = {Giardina, E and Mandich, P and Ghidoni, R and Ticozzi, N and Rossi, G and Fenoglio, C and Tiziano, FD and Esposito, F and Capellari, S and Nacmias, B and Mineri, R and Campopiano, R and Di Pilla, L and Sammarone, F and Zampatti, S and Peconi, C and De Angelis, F and Palmieri, I and Galandra, C and Nicodemo, E and Origone, P and Gotta, F and Ponti, C and Nicsanu, R and Benussi, L and Peverelli, S and Ratti, A and Ricci, M and Di Fede, G and Magri, S and Serpente, M and Lattante, S and Domi, T and Carrera, P and Saltimbanco, E and Bagnoli, S and Ingannato, A and Albanese, A and Tagliavini, F and Lodi, R and Caltagirone, C and Gambardella, S and Valente, EM and Silani, V}, title = {Distribution of the C9orf72 hexanucleotide repeat expansion in healthy subjects: a multicenter study promoted by the Italian IRCCS network of neuroscience and neurorehabilitation.}, journal = {Frontiers in neurology}, volume = {15}, number = {}, pages = {1284459}, pmid = {38356886}, issn = {1664-2295}, abstract = {INTRODUCTION: High repeat expansion (HRE) alleles in C9orf72 have been linked to both amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD); ranges for intermediate allelic expansions have not been defined yet, and clinical interpretation of molecular data lacks a defined genotype-phenotype association. In this study, we provide results from a large multicenter epidemiological study reporting the distribution of C9orf72 repeats in healthy elderly from the Italian population.

METHODS: A total of 967 samples were collected from neurologically evaluated healthy individuals over 70 years of age in the 13 institutes participating in the RIN (IRCCS Network of Neuroscience and Neurorehabilitation) based in Italy. All samples were genotyped using the AmplideXPCR/CE C9orf72 Kit (Asuragen, Inc.), using standardized protocols that have been validated through blind proficiency testing.

RESULTS: All samples carried hexanucleotide G4C2 expansion alleles in the normal range. All samples were characterized by alleles with less than 25 repeats. In particular, 93.7% of samples showed a number of repeats ≤10, 99.9% ≤20 repeats, and 100% ≤25 repeats.

CONCLUSION: This study describes the distribution of hexanucleotide G4C2 expansion alleles in an Italian healthy population, providing a definition of alleles associated with the neurological healthy phenotype. Moreover, this study provides an effective model of federation between institutes, highlighting the importance of sharing genomic data and standardizing analysis techniques, promoting translational research. Data derived from the study may improve genetic counseling and future studies on ALS/FTD.}, } @article {pmid38356047, year = {2024}, author = {Wimmer, N and Müller, HP and Metze, P and Rasche, V and Ludolph, AC and Kassubek, J}, title = {The central pattern of weakness of ALS: Morphological correlates in whole-body muscle MRI.}, journal = {Annals of clinical and translational neurology}, volume = {11}, number = {4}, pages = {1000-1010}, pmid = {38356047}, issn = {2328-9503}, mesh = {Humans ; *Magnetic Resonance Imaging/methods ; *Amyotrophic Lateral Sclerosis/diagnostic imaging/pathology ; Whole Body Imaging ; Muscle, Skeletal/pathology ; Paresis ; }, abstract = {OBJECTIVE: Monosynaptically cortically innervated α-motoneurons are early and strongly involved in amyotrophic lateral sclerosis (ALS). Consequently, the muscles that receive the strongest direct corticomotoneuronal input are the clinically most affected. To objectify this concept in vivo through morphological image correlates, whole-body magnetic resonance imaging (MRI) with muscle signal analysis was performed in patients with ALS compared to healthy controls.

METHODS: Modified Dixon-based whole-body MRI was acquired in patients with ALS (n = 33) and matched healthy controls (n = 30). Manual labeling of limb muscle MRI was performed, and a specific subset of nine muscles, selected as pairs of muscle groups with different corticomotoneuronal input, was analyzed per subject based on their volume, fat fraction, and functional remaining muscle area (fRMA).

RESULTS: Statistical analysis of 978 muscles in total revealed significantly decreased volumes, decreased fRMA, and increased fat fraction in the muscles of patients with ALS compared to controls. The clinical degree of pareses of directly innervated muscles was significantly worse than that of less directly innervated muscles in each comparison. The muscles receiving stronger direct corticomotoneuronal input showed more pronounced morphological involvement compared to those with less monosynaptic corticomotoneuronal input (fRMA, significant in three pairwise comparisons).

INTERPRETATION: In conclusion, whole-body MRI-based muscle analysis provided additional evidence for a characteristic pattern of pareses in ALS. This technical approach (parameterization and quantification of muscle alterations from MRI) to patients with ALS could pave the way for the future establishment of a diagnostic algorithm of muscle MRI for ALS and may serve as a biomarker.}, } @article {pmid38355792, year = {2024}, author = {Hruska-Plochan, M and Wiersma, VI and Betz, KM and Mallona, I and Ronchi, S and Maniecka, Z and Hock, EM and Tantardini, E and Laferriere, F and Sahadevan, S and Hoop, V and Delvendahl, I and Pérez-Berlanga, M and Gatta, B and Panatta, M and van der Bourg, A and Bohaciakova, D and Sharma, P and De Vos, L and Frontzek, K and Aguzzi, A and Lashley, T and Robinson, MD and Karayannis, T and Mueller, M and Hierlemann, A and Polymenidou, M}, title = {A model of human neural networks reveals NPTX2 pathology in ALS and FTLD.}, journal = {Nature}, volume = {626}, number = {8001}, pages = {1073-1083}, pmid = {38355792}, issn = {1476-4687}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism/pathology ; *C-Reactive Protein/metabolism ; *DNA-Binding Proteins/deficiency/metabolism ; *Frontotemporal Lobar Degeneration/metabolism/pathology ; *Nerve Net/metabolism/pathology ; *Nerve Tissue Proteins/metabolism ; Neural Stem Cells/cytology ; Neuroglia/cytology ; *Neurons/cytology/metabolism ; Reproducibility of Results ; }, abstract = {Human cellular models of neurodegeneration require reproducibility and longevity, which is necessary for simulating age-dependent diseases. Such systems are particularly needed for TDP-43 proteinopathies[1], which involve human-specific mechanisms[2-5] that cannot be directly studied in animal models. Here, to explore the emergence and consequences of TDP-43 pathologies, we generated induced pluripotent stem cell-derived, colony morphology neural stem cells (iCoMoNSCs) via manual selection of neural precursors[6]. Single-cell transcriptomics and comparison to independent neural stem cells[7] showed that iCoMoNSCs are uniquely homogenous and self-renewing. Differentiated iCoMoNSCs formed a self-organized multicellular system consisting of synaptically connected and electrophysiologically active neurons, which matured into long-lived functional networks (which we designate iNets). Neuronal and glial maturation in iNets was similar to that of cortical organoids[8]. Overexpression of wild-type TDP-43 in a minority of neurons within iNets led to progressive fragmentation and aggregation of the protein, resulting in a partial loss of function and neurotoxicity. Single-cell transcriptomics revealed a novel set of misregulated RNA targets in TDP-43-overexpressing neurons and in patients with TDP-43 proteinopathies exhibiting a loss of nuclear TDP-43. The strongest misregulated target encoded the synaptic protein NPTX2, the levels of which are controlled by TDP-43 binding on its 3' untranslated region. When NPTX2 was overexpressed in iNets, it exhibited neurotoxicity, whereas correcting NPTX2 misregulation partially rescued neurons from TDP-43-induced neurodegeneration. Notably, NPTX2 was consistently misaccumulated in neurons from patients with amyotrophic lateral sclerosis and frontotemporal lobar degeneration with TDP-43 pathology. Our work directly links TDP-43 misregulation and NPTX2 accumulation, thereby revealing a TDP-43-dependent pathway of neurotoxicity.}, } @article {pmid38354985, year = {2024}, author = {Zamani, A and Thomas, E and Wright, DK}, title = {Sex biology in amyotrophic lateral sclerosis.}, journal = {Ageing research reviews}, volume = {95}, number = {}, pages = {102228}, doi = {10.1016/j.arr.2024.102228}, pmid = {38354985}, issn = {1872-9649}, mesh = {Humans ; Male ; Female ; *Amyotrophic Lateral Sclerosis/epidemiology/genetics ; Brain/pathology ; Biology ; }, abstract = {Although sex differences in amyotrophic lateral sclerosis (ALS) have not been studied systematically, numerous clinical and preclinical studies have shown sex to be influential in disease prognosis. Moreover, with the development of advanced imaging tools, the difference between male and female brain in structure and function and their response to neurodegeneration are more definitive. As discussed in this review, ALS patients exhibit a sex bias pertaining to the features of the disease, and their clinical, pathological, (and pathophysiological) phenotypes. Several epidemiological studies have indicated that this sex disparity stems from various aetiologies, including sex-specific brain structure and neural functioning, genetic predisposition, age, gonadal hormones, susceptibility to traumatic brain injury (TBI)/head trauma and lifestyle factors.}, } @article {pmid38354672, year = {2024}, author = {Aradhye, P and Jha, S and Saha, P and Patwardhan, RS and Noothalapati, H and Krishna, CM and Patwardhan, S}, title = {Distinct spectral signatures unfold ECM stiffness-triggered biochemical changes in breast cancer cells.}, journal = {Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy}, volume = {311}, number = {}, pages = {123994}, doi = {10.1016/j.saa.2024.123994}, pmid = {38354672}, issn = {1873-3557}, mesh = {Humans ; Female ; *Breast Neoplasms/metabolism ; Extracellular Matrix/chemistry/metabolism ; Collagen/analysis ; }, abstract = {Cancer progression often accompanies the stiffening of extracellular matrix (ECM) in and around the tumor, owing to extra deposition and cross-linking of collagen. Stiff ECM has been linked with poor prognosis and is known to fuel invasion and metastasis, notably in breast cancer. However, the underlying biochemical or metabolic changes and the cognate molecular signatures remain elusive. Here, we explored Raman spectroscopy to unveil the spectral fingerprints of breast cancer cells in response to extracellular mechanical cues. Using stiffness-tuneable hydrogels, we showed that cells grown on stiff ECM displayed morphological changes with high proliferation. We further demonstrated that Raman Spectroscopy, a label-free and non-invasive technique, could provide comprehensive information about the biochemical environment of breast cancer cells in response to varying ECM stiffness. Raman spectroscopic analysis classified the cells into distinct clusters based on principal component-based linear discriminant analysis (PC-LDA). Multivariate curve resolution-alternating least squares (MCR-ALS) analysis indicated that cells cultured on stiff ECM exhibited elevated nucleic acid content and lesser lipids. Interestingly, increased intensity of Raman bands corresponding to cytochrome-c was also observed in stiff ECM conditions, suggesting mitochondrial modulation. The key findings harboured by spectral profiles were also corroborated by transmission electron microscopy, confirming altered metabolic status as reflected by increased mitochondria number and decreased lipid droplets in response to ECM stiffening. Collectively, these findings not only give the spectral signatures for mechanoresponse but also provide the landscape of biochemical changes in response to ECM stiffening.}, } @article {pmid38354654, year = {2024}, author = {Li, M and Zhao, Z and Zhang, Y and Guo, X and Zhang, Y and Wang, J and Liu, Y and Yang, L and Mou, W and Zhang, X and Gao, H}, title = {Chemometrics combined with comprehensive two-dimensional gas chromatography-mass spectrometry for the identification of Baijiu vintage.}, journal = {Food chemistry}, volume = {444}, number = {}, pages = {138690}, doi = {10.1016/j.foodchem.2024.138690}, pmid = {38354654}, issn = {1873-7072}, mesh = {Gas Chromatography-Mass Spectrometry/methods ; *Chemometrics ; Least-Squares Analysis ; }, abstract = {The identification of baijiu vintage is crucial for quality assessment and economic value determination. However, its complex composition and multifaceted influences pose significant technical challenges, necessitating research into its aging mechanisms and the development of related identification methods. This study utilized Chemometrics in conjunction with GC × GC-TOFMS for Baijiu Vintage identification. Data compression achieved a reduction of over 1000-fold without compromising key information, enabling analysis on many samples and get their changing regular in a big matrix by MCR. Subsequently, MCR-ALS facilitated the extraction of physical and chemical meaningful information related to baijiu vintage. Key MCR principal components suitable for qualitative and quantitative assessments were selected using CARS-PLS. The regression model demonstrated errors of less than one year. Furthermore, a PLS-DA model provided 30 MCR principal components as potential markers. The research results provide technical support for baijiu vintage identification and lay the groundwork for studying the changing patterns of flavor compounds in baijiu.}, } @article {pmid38353166, year = {2024}, author = {Hart, AA and Swenson, A and Narayanan, NS and Simmering, JE}, title = {Rurality modifies the association between symptoms and the diagnosis of amyotrophic lateral sclerosis.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {25}, number = {5-6}, pages = {517-527}, pmid = {38353166}, issn = {2167-9223}, support = {K12 TR004382/TR/NCATS NIH HHS/United States ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/epidemiology ; Male ; Female ; Middle Aged ; *Rural Population/statistics & numerical data ; Aged ; Adult ; United States/epidemiology ; Urban Population/statistics & numerical data ; }, abstract = {OBJECTIVE: We utilized national claims-based data to identify the change in odds of diagnosis of ALS following possible-ALS-symptoms-and whether the change varies in urban/rural areas.

METHODS: Insurance claims were obtained from the Merative MarketScan databases, 2001-2021 in the United States. Individuals with incident ALS were identified and matched on age, sex, and enrollment period to individuals without ALS. For all individuals, claims for 8 possible-ALS-symptoms in the time before any ALS diagnosis were identified. We then used conditional logistic regression to estimate the odds of being diagnosed with ALS following these symptoms and whether the association varied by urban/rural location.

RESULTS: 19,226 individuals with ALS were matched to 96,126 controls. Patients with ALS were more likely to live in an urban area (87.0% vs 84.5%). Of those with ALS 84% had 1+ of our 8 possible-ALS-symptom compared to 51% of controls. After adjustment for confounders, having possible-ALS-symptoms increased the odds of a future ALS diagnosis by nearly 5-fold. A dose-response pattern was present with increasing odds as the number of symptoms increased. In all models, urban areas were associated with increased odds of diagnosis with ALS while the effect of having a symptom was smaller in urban places. Urban cases of ALS are diagnosed at younger ages.

CONCLUSIONS: These results suggest symptoms may appear and be noted years before the diagnosis of ALS. Additionally, rural patients are diagnosed at later ages with a greater dependence on symptoms than urban patients. These results highlight potential improvements for screening for ALS.}, } @article {pmid38352429, year = {2024}, author = {Alessandrini, F and Wright, M and Kurosaki, T and Maquat, LE and Kiskinis, E}, title = {ALS-Associated TDP-43 Dysfunction Compromises UPF1-Dependent mRNA Metabolism Pathways Including Alternative Polyadenylation and 3'UTR Length.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2024.01.31.578311}, pmid = {38352429}, issn = {2692-8205}, abstract = {UPF1-mediated decay entails several mRNA surveillance pathways that play a crucial role in cellular homeostasis. However, the precise role of UPF1 in postmitotic neurons remains unresolved, as does its activity in amyotrophic lateral sclerosis (ALS), a devastating neurodegenerative disease characterized by TDP-43 pathology and disrupted mRNA metabolism. Here, we used human iPSC-derived spinal motor neurons (MNs) to identify mRNAs subject to UPF1 degradation by integrating RNA-seq before and after UPF1 knockdown with RIP-seq to identify RNAs that co-immunoprecipitate with the active form of phosphorylated UPF1. We define a stringent set of bona fide UPF1 targets in MNs that are functionally enriched for autophagy and structurally enriched for GC-rich and long 3' UTRs but not for premature termination codon (PTC)-containing transcripts. TDP-43 depletion in iPSC-derived MNs reduces UPF1 phosphorylation and consequently post-transcriptional upregulation of UPF1 targets, suggesting that TDP-43 dysfunction compromises UPF1-mediated mRNA surveillance. Intriguingly, our datasets reveal that UPF1 and TDP-43 regulate alternative polyadenylation and 3'UTR length of mRNAs associated with synaptic and axonal function, a process that we find to be compromised in ALS models in vitro and ALS patient tissue. Our study provides a comprehensive description of UPF1-mediated mRNA decay activity in neurons, reveals overlapping roles between UPF1 and TDP-43 in regulating 3'UTR length, and offers novel insight into the intricate interplay between RNA metabolism and neurodegeneration in ALS.}, } @article {pmid38352403, year = {2024}, author = {Sirtori, R and Gregoire, M and Collins, A and Santangelo, S and Chatragadda, B and Cullen, R and Ratti, A and Fallini, C}, title = {Altered nuclear envelope homeostasis is a key pathogenic event in C9ORF72-linked ALS/FTD.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2024.02.01.578318}, pmid = {38352403}, issn = {2692-8205}, support = {P20 GM103430/GM/NIGMS NIH HHS/United States ; R01 NS116143/NS/NINDS NIH HHS/United States ; }, abstract = {ALS and FTD are complex neurodegenerative disorders that primarily affects motor neurons in the brain and spinal cord, and cortical neurons in the frontal lobe. Although the pathogenesis of ALS/FTD is unclear, recent research spotlights nucleocytoplasmic transport impairment, DNA damage, and nuclear abnormalities as drivers of neuronal death. In this study, we show that loss of nuclear envelope (NE) integrity is a key pathology associated with nuclear pore complex (NPC) injury in C9ORF72 mutant neurons. Importantly, we show that mechanical stresses generated by cytoskeletal forces on the NE can lead to NPC injury, loss of nuclear integrity, and accumulation of DNA damage. Importantly, we demonstrate that restoring NE tensional homeostasis, by disconnecting the nucleus from the cytoskeleton, can rescue NPC injury and reduce DNA damage in C9ORF72 mutant cells. Together, our data suggest that modulation of NE homeostasis and repair may represent a novel and promising therapeutic target for ALS/FTD.}, } @article {pmid38352376, year = {2024}, author = {Amado, DA and Robbins, AB and Smith, AR and Whiteman, KR and Chillon Bosch, G and Chen, Y and Fuller, JA and Izda, A and Nelson, S and Dichter, AI and Monteys, AM and Davidson, BL}, title = {AAV-based delivery of RNAi targeting Ataxin-2 improves survival, strength, and pathology in mouse models of rapidly and slowly progressive sporadic ALS.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2024.01.31.578314}, pmid = {38352376}, issn = {2692-8205}, support = {K08 NS114106/NS/NINDS NIH HHS/United States ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is characterized by motor neuron death due to nuclear loss and cytoplasmic aggregation of the splice factor TDP-43. Pathologic TDP-43 associates with stress granules (SGs) and downregulating the SG-associated protein Ataxin-2 (Atxn2) using antisense oligonucleotides (ASO) prolongs survival in the TAR4/4 sporadic ALS mouse model, a strategy now in clinical trials. Here, we used AAV-mediated RNAi delivery to achieve lasting and targeted Atxn2 knockdown after a single injection. To achieve this, a novel AAV with improved transduction potency of our target cells was used to deliver Atxn2 -targeting miRNAs. Mouse dosing studies demonstrated 55% Atxn2 knockdown in frontal cortex and 25% knockdown throughout brainstem and spinal cord after intracerebroventricular injection at a dose 40x lower than used in other recent studies. In TAR4/4 mice, miAtxn2 treatment increased mean and median survival by 54% and 45% respectively (p<0.0003). Mice showed robust improvement across strength-related measures ranging from 24-75%. Interestingly, treated mice showed increased vertical activity above wildtype, suggesting unmasking of an FTD phenotype with improved strength. Histologically, lower motor neuron survival improved with a concomitant reduction in CNS inflammatory markers. Additionally, phosphorylated TDP-43 was reduced to wildtype levels. Bulk RNA sequencing revealed correction of 153 genes in the markedly dysregulated transcriptome of mutant mice, several of which are described in the human ALS literature. In slow progressing hemizygous mice, treatment rescued weight loss and improved gait at late time points. Cumulatively the data support the utility of AAV-mediated RNAi against Atxn2 as a robust and translatable treatment strategy for sporadic ALS.}, } @article {pmid38352350, year = {2024}, author = {Gomez, N and Hsieh, C and Li, X and Dykstra, M and Waksmacki, J and Altheim, C and Bechar, Y and Klim, J and Zaepfel, B and Rothstein, J and Tank, EE and Barmada, SJ}, title = {Counter-regulation of RNA stability by UPF1 and TDP43.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2024.01.31.578310}, pmid = {38352350}, issn = {2692-8205}, support = {R01 NS097542/NS/NINDS NIH HHS/United States ; R56 NS128110/NS/NINDS NIH HHS/United States ; T32 GM145470/GM/NIGMS NIH HHS/United States ; }, abstract = {RNA quality control is crucial for proper regulation of gene expression. Disruption of nonsense mediated mRNA decay (NMD), the primary RNA decay pathway responsible for the degradation of transcripts containing premature termination codons (PTCs), can disrupt development and lead to multiple diseases in humans and other animals. Similarly, therapies targeting NMD may have applications in hematological, neoplastic and neurological disorders. As such, tools capable of accurately quantifying NMD status could be invaluable for investigations of disease pathogenesis and biomarker identification. Toward this end, we assemble, validate, and apply a next-generation sequencing approach (NMDq) for identifying and measuring the abundance of PTC-containing transcripts. After validating NMDq performance and confirming its utility for tracking RNA surveillance, we apply it to determine pathway activity in two neurodegenerative diseases, amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) characterized by RNA misprocessing and abnormal RNA stability. Despite the genetic and pathologic evidence implicating dysfunctional RNA metabolism, and NMD in particular, in these conditions, we detected no significant differences in PTC-encoding transcripts in ALS models or disease. Contrary to expectations, overexpression of the master NMD regulator UPF1 had little effect on the clearance of transcripts with PTCs, but rather restored RNA homeostasis through differential use and decay of alternatively poly-adenylated isoforms. Together, these data suggest that canonical NMD is not a significant contributor to ALS/FTD pathogenesis, and that UPF1 promotes neuronal survival by regulating transcripts with abnormally long 3'UTRs.}, } @article {pmid38351547, year = {2024}, author = {Park, JJ and Chow, SM and Epskamp, S and Molenaar, PCM}, title = {Subgrouping with Chain Graphical VAR Models.}, journal = {Multivariate behavioral research}, volume = {59}, number = {3}, pages = {543-565}, pmid = {38351547}, issn = {1532-7906}, support = {U24 AA027684/AA/NIAAA NIH HHS/United States ; UL1 TR002014/TR/NCATS NIH HHS/United States ; }, mesh = {Humans ; *Monte Carlo Method ; *Models, Statistical ; *Computer Simulation/statistics & numerical data ; Data Interpretation, Statistical ; Least-Squares Analysis ; }, abstract = {Recent years have seen the emergence of an "idio-thetic" class of methods to bridge the gap between nomothetic and idiographic inference. These methods describe nomothetic trends in idiographic processes by pooling intraindividual information across individuals to inform group-level inference or vice versa. The current work introduces a novel "idio-thetic" model: the subgrouped chain graphical vector autoregression (scGVAR). The scGVAR is unique in its ability to identify subgroups of individuals who share common dynamic network structures in both lag(1) and contemporaneous effects. Results from Monte Carlo simulations indicate that the scGVAR shows promise over similar approaches when clusters of individuals differ in their contemporaneous dynamics and in showing increased sensitivity in detecting nuanced group differences while keeping Type-I error rates low. In contrast, a competing approach-the Alternating Least Squares VAR (ALS VAR) performs well when groups were separated by larger distances. Further considerations are provided regarding applications of the ALS VAR and scGVAR on real data and the strengths and limitations of both methods.}, } @article {pmid38350967, year = {2024}, author = {Rodriguez-Mogeda, C and van Ansenwoude, CMJ and van der Molen, L and Strijbis, EMM and Mebius, RE and de Vries, HE}, title = {The role of CD56[bright] NK cells in neurodegenerative disorders.}, journal = {Journal of neuroinflammation}, volume = {21}, number = {1}, pages = {48}, pmid = {38350967}, issn = {1742-2094}, mesh = {Humans ; Killer Cells, Natural ; Cytokines ; Cell Differentiation ; *Antineoplastic Agents ; *Neurodegenerative Diseases ; }, abstract = {Emerging evidence suggests a potential role for natural killer (NK) cells in neurodegenerative diseases, such as multiple sclerosis, Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis. However, the precise function of NK cells in these diseases remains ambiguous. The existence of two NK cell subsets, CD56[bright] and CD56[dim] NK cells, complicates the understanding of the contribution of NK cells in neurodegeneration as their functions within the context of neurodegenerative diseases may differ significantly. CD56[bright] NK cells are potent cytokine secretors and are considered more immunoregulatory and less terminally differentiated than their mostly cytotoxic CD56[dim] counterparts. Hence, this review focusses on NK cells, specifically on CD56[bright] NK cells, and their role in neurodegenerative diseases. Moreover, it explores the mechanisms underlying their ability to enter the central nervous system. By consolidating current knowledge, we aim to provide a comprehensive overview on the role of CD56[bright] NK cells in neurodegenerative diseases. Elucidating their impact on neurodegeneration may have implications for future therapeutic interventions, potentially ameliorating disease pathogenesis.}, } @article {pmid38350049, year = {2024}, author = {Urushitani, M and Nakamura, R}, title = {Hypermetabolism in Amyotrophic Lateral Sclerosis: Step Ahead Toward Global Consensus.}, journal = {Neurology}, volume = {102}, number = {5}, pages = {e209179}, doi = {10.1212/WNL.0000000000209179}, pmid = {38350049}, issn = {1526-632X}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy ; Consensus ; }, } @article {pmid38350046, year = {2024}, author = {Holdom, CJ and Janse van Mantgem, MR and He, J and Howe, SL and McCombe, PA and Fan, D and van den Berg, LH and Henderson, RD and van Eijk, R and Steyn, FJ and Ngo, ST}, title = {Variation in Resting Metabolic Rate Affects Identification of Metabolic Change in Geographically Distinct Cohorts of Patients With ALS.}, journal = {Neurology}, volume = {102}, number = {5}, pages = {e208117}, doi = {10.1212/WNL.0000000000208117}, pmid = {38350046}, issn = {1526-632X}, mesh = {Humans ; *Basal Metabolism ; Energy Metabolism ; *Amyotrophic Lateral Sclerosis/epidemiology/metabolism ; Australia/epidemiology ; Body Composition ; }, abstract = {BACKGROUND AND OBJECTIVES: Altered metabolism is observed in amyotrophic lateral sclerosis (ALS). However, without a standardized methodology to define metabolic changes, our understanding of factors contributing to and the clinical significance of altered metabolism in ALS is limited.

METHODS: We aimed to determine how geographic variation in metabolic rates influences estimates and accuracy of predicted resting energy expenditure (REE) in patients with ALS and controls, while validating the effectiveness of cohort-specific approaches in predicting altered metabolic rate in ALS. Participants from 3 geographically distinct sites across Australia, China, and the Netherlands underwent REE assessments, and we considered 22 unique equations for estimating REE. Analyses evaluated equation performance and the influence of demographics on metabolic status. Comparisons were made using standardized and local reference values to identify metabolic alterations.

RESULTS: 606 participants were included from Australia (patients with ALS: 140, controls: 154), the Netherlands (patients with ALS: 79, controls: 37) and China (patients with ALS: 67, controls: 129). Measured REE was variable across geographic cohorts, with fat-free mass contributing to this variation across all patients (p = 0.002 to p < 0.001). Of the 22 predication equations assessed, the Sabounchi Structure 4 (S4) equation performed relatively well across all control cohorts. Use of prediction thresholds generated using data from Australian controls generally increased the prevalence of hypermetabolism in Chinese (55%, [43%-67%]) and Dutch (44%, [33%-55%]) cases when compared with Australian cases (30%, [22%-38%]). Adjustment of prediction thresholds to consider geographically distinct characteristics from matched control cohorts resulted in a decrease in the proportion of hypermetabolic cases in Chinese and Dutch cohorts (25%-31% vs 55% and 20%-34% vs 43%-44%, respectively), and increased prevalence of hypometabolism in Dutch cases with ALS (1% to 8%-10%).

DISCUSSION: The identification of hypermetabolism in ALS is influenced by the formulae and demographic-specific prediction thresholds used for defining alterations in metabolic rate. A consensus approach is needed for identification of metabolic changes in ALS and will facilitate improved understanding of the cause and clinical significance of this in ALS.}, } @article {pmid38349516, year = {2024}, author = {Xin, Z and Xin, C and Huo, J and Liu, Q and Dong, H and Li, R and Liu, Y}, title = {Neuroprotective Effect of a Multistrain Probiotic Mixture in SOD1[G93A] Mice by Reducing SOD1 Aggregation and Targeting the Microbiota-Gut-Brain Axis.}, journal = {Molecular neurobiology}, volume = {61}, number = {12}, pages = {10051-10071}, pmid = {38349516}, issn = {1559-1182}, support = {H2021206310//the Natural Science Foundation of Hebei Province/ ; zh2018004//the Key Project of Technical Health Research and Achievement Transformation of Hebei Provincial Department of Health/ ; }, mesh = {Animals ; *Probiotics/pharmacology ; *Gastrointestinal Microbiome/drug effects ; *Superoxide Dismutase-1/metabolism/genetics ; *Mice, Transgenic ; *Neuroprotective Agents/pharmacology ; *Amyotrophic Lateral Sclerosis/pathology ; Brain-Gut Axis/drug effects/physiology ; Mice ; Autophagy/drug effects ; Brain/drug effects/metabolism ; Spinal Cord/drug effects/metabolism/pathology ; Protein Aggregates/drug effects ; Mice, Inbred C57BL ; Male ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by the selective loss of motor neurons. A bidirectional communication system known as the "microbiota-gut-brain" axis has a regulatory function in neurodegenerative disorders. The impact of probiotics on ALS through the "microbiota-gut-brain" axis remains uncertain. A longitudinal investigation was conducted to examine the alterations in the structure of the ileum and colon in mutant superoxide dismutase 1 (SOD1[G93A]) transgenic mice models of ALS by using immunofluorescence and Western blotting. Subsequently, the mice were administered a multistrain probiotic mixture (LBE) or vehicle orally, starting from 60 days of age until the terminal stage of the disease. The effects of these agents on the behavior, gut microbiota, microbial metabolites, and pathological processes of the spinal and intestine of SOD1[G93A] mice were analyzed, with a focus on exploring potential protective mechanisms. SOD1[G93A] mice exhibit various structural abnormalities in the intestine. Oral administration of LBE improved the proinflammatory response, reduced aberrant superoxide dismutase 1 (SOD1) aggregation, and protected neuronal cells in the intestine and spinal cord of SOD1[G93A] mice. Furthermore, LBE treatment resulted in a change in intestinal microbiota, an increase in short-chain fatty acid levels, and an enhancement in autophagy flux. SOD1[G93A] mice exhibited various structural abnormalities in the intestine. LBE can improve the proinflammatory response, reduce aberrant SOD1 aggregation, and protect neuronal cells in the spinal cord and intestine of SOD1[G93A] mice. The positive effect of LBE can be attributed to increased short-chain fatty acids and enhanced autophagy flux.}, } @article {pmid38349514, year = {2024}, author = {Xu, Y and Lin, F and Liao, G and Sun, J and Chen, W and Zhang, L}, title = {Ripks and Neuroinflammation.}, journal = {Molecular neurobiology}, volume = {61}, number = {9}, pages = {6771-6787}, pmid = {38349514}, issn = {1559-1182}, support = {81971098//National Natural Science Foundation of China/ ; 82104144//National Natural Science Foundation of China/ ; }, mesh = {*Receptor-Interacting Protein Serine-Threonine Kinases/metabolism ; Humans ; Animals ; *Neuroinflammatory Diseases/metabolism/pathology ; Inflammation/pathology/metabolism ; }, abstract = {Neuroinflammation is an immune response in the central nervous system and poses a significant threat to human health. Studies have shown that the receptor serine/threonine protein kinase family (RIPK) family, a popular research target in inflammation, has been shown to play an essential role in neuroinflammation. It is significant to note that the previous reviews have only examined the link between RIPK1 and neuroinflammation. However, it has yet to systematically analyze the relationship between the RIPK family and neuroinflammation. Activation of RIPK1 promotes neuroinflammation. RIPK1 and RIPK3 are responsible for the control of cell death, including apoptosis, necrosis, and inflammation. RIPK1 and RIPK3 regulate inflammatory responses through the release of damage in necroptosis. RIPK1 and RIPK3 regulate inflammatory responses by releasing damage-associated molecular patterns (DAMPs) during necrosis. In addition, activated RIPK1 nuclear translocation and its interaction with the BAF complex leads to upregulation of chromatin modification and inflammatory gene expression, thereby triggering inflammation. Although RIPK2 is not directly involved in regulating cell death, it is considered an essential target for treating neurological inflammation. When the peptidoglycan receptor detects peptidoglycan IE-DAP or MDP in bacteria, it prompts NOD1 and NOD2 to recruit RIPK2 and activate the XIAP E3 ligase. This leads to the K63 ubiquitination of RIPK2. This is followed by LUBAC-mediated linear ubiquitination, which activates NF-KB and MAPK pathways to produce cytokines and chemokines. In conclusion, there are seven known members of the RIPK family, but RIPK4, RIPK5, RIPK6, and RIPK7 have not been linked to neuroinflammation. This article seeks to explore the potential of RIPK1, RIPK2, and RIPK3 kinases as therapeutic interventions for neuroinflammation, which is associated with Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), ischemic stroke, Parkinson's disease (PD), multiple sclerosis (MS), and traumatic brain injury (TBI).}, } @article {pmid38349395, year = {2024}, author = {Soni, S and Lukhey, MS and Thawkar, BS and Chintamaneni, M and Kaur, G and Joshi, H and Ramniwas, S and Tuli, HS}, title = {A current review on P2X7 receptor antagonist patents in the treatment of neuroinflammatory disorders: a patent review on antagonists.}, journal = {Naunyn-Schmiedeberg's archives of pharmacology}, volume = {397}, number = {7}, pages = {4643-4656}, pmid = {38349395}, issn = {1432-1912}, mesh = {*Patents as Topic ; Humans ; *Receptors, Purinergic P2X7/metabolism ; *Purinergic P2X Receptor Antagonists/therapeutic use/pharmacology ; Animals ; *Neuroinflammatory Diseases/drug therapy ; }, abstract = {Chronic inflammation is defined by an activated microglial state linked to all neurological disorders, including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis (a motor neuron disease that affects the brain and spinal cord). P2X7 receptors (P2X7R) are ATP-activated ion-gated channels present on microglial surfaces. Prolonged ATP release under pathological settings results in sustained P2X7R activation, which leads to inflammasome development and cytokine release. P2X7R and its enabling roles have recently been linked to neurodegenerative diseases, making it a potential research subject. This research provides an overview of current patents for chemicals, biologics, and medicinal applications. The World Intellectual Property Organization (WIPO), European Patent Office (EPO, Espacenet), and the United States Patent and Trademark Office (USPTO) databases were searched for patents using the keywords "P2X7R and Neuroinflammation." During the study period from 2015 to 2021, 103 patents were examined. The countries that protected these innovations were the United States, PCT (Patent Cooperation Treaty states), Europe, Canada, Australia, and India. Janssen Pharmaceutica NV had the most applications, followed by Acetelion Pharmaceuticals LTD., Renovis Inc., Kelly Michael G, Kincaid Jhon, Merck Patent GMBH, H Lundbeck A/S, and many more. The P2X7R is a possible diagnostic and therapeutic target for cancer, pain disorders, and inflammation. For P2X7 R, several compounds have been discovered and are presently the subject of clinical trial investigations. This study featured patents for P2X7R antagonists, which help treat conditions including neuroinflammation.}, } @article {pmid38348223, year = {2024}, author = {Orfali, R and Alwatban, AZ and Orfali, RS and Lau, L and Chea, N and Alotaibi, AM and Nam, YW and Zhang, M}, title = {Oxidative stress and ion channels in neurodegenerative diseases.}, journal = {Frontiers in physiology}, volume = {15}, number = {}, pages = {1320086}, pmid = {38348223}, issn = {1664-042X}, support = {R33 NS101182/NS/NINDS NIH HHS/United States ; }, abstract = {Numerous neurodegenerative diseases result from altered ion channel function and mutations. The intracellular redox status can significantly alter the gating characteristics of ion channels. Abundant neurodegenerative diseases associated with oxidative stress have been documented, including Parkinson's, Alzheimer's, spinocerebellar ataxia, amyotrophic lateral sclerosis, and Huntington's disease. Reactive oxygen and nitrogen species compounds trigger posttranslational alterations that target specific sites within the subunits responsible for channel assembly. These alterations include the adjustment of cysteine residues through redox reactions induced by reactive oxygen species (ROS), nitration, and S-nitrosylation assisted by nitric oxide of tyrosine residues through peroxynitrite. Several ion channels have been directly investigated for their functional responses to oxidizing agents and oxidative stress. This review primarily explores the relationship and potential links between oxidative stress and ion channels in neurodegenerative conditions, such as cerebellar ataxias and Parkinson's disease. The potential correlation between oxidative stress and ion channels could hold promise for developing innovative therapies for common neurodegenerative diseases.}, } @article {pmid38348026, year = {2024}, author = {Tang, C and Lei, X and Ding, Y and Yang, S and Ma, Y and He, D}, title = {Causal relationship between immune cells and neurodegenerative diseases: a two-sample Mendelian randomisation study.}, journal = {Frontiers in immunology}, volume = {15}, number = {}, pages = {1339649}, pmid = {38348026}, issn = {1664-3224}, mesh = {Humans ; *Neurodegenerative Diseases/genetics ; *Amyotrophic Lateral Sclerosis/genetics ; *Alzheimer Disease/genetics ; *Parkinson Disease/genetics ; Causality ; *Multiple Sclerosis/genetics ; }, abstract = {BACKGROUND: There is increasing evidence that the types of immune cells are associated with various neurodegenerative diseases. However, it is currently unclear whether these associations reflect causal relationships.

OBJECTIVE: To elucidate the causal relationship between immune cells and neurodegenerative diseases, we conducted a two-sample Mendelian randomization (MR) analysis.

MATERIALS AND METHODS: The exposure and outcome GWAS data used in this study were obtained from an open-access database (https://gwas.mrcieu.ac.uk/), the study employed two-sample MR analysis to assess the causal relationship between 731 immune cell features and four neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS). All immune cell data was obtained from Multiple MR methods were used to minimize bias and obtain reliable estimates of the causal relationship between the variables of interest and the outcomes. Instrumental variable selection criteria were restricted to ensure the accuracy and effectiveness of the causal relationship between species of immune cells and the risk of these neurodegenerative diseases.

RESULTS: The study identified potential causal relationships between various immune cells and different neurodegenerative diseases. Specifically, we found that 8 different types of immune cells have potential causal relationships with AD, 1 type of immune cells has potential causal relationships with PD, 6 different types of immune cells have potential causal relationships with ALS, and 6 different types of immune cells have potential causal relationships with MS.

CONCLUSION: Our study, through genetic means, demonstrates close causal associations between the specific types of immune cells and AD, PD, ALS and MS, providing useful guidance for future clinical researches.}, } @article {pmid38347888, year = {2024}, author = {Aoun, SM and O'Brien, MR and Knighting, K}, title = {Using the Carers' Alert Thermometer tool to identify needs and support family caregivers of people with motor neurone disease: moving beyond needs assessments.}, journal = {Palliative care and social practice}, volume = {18}, number = {}, pages = {26323524241228306}, pmid = {38347888}, issn = {2632-3524}, abstract = {BACKGROUND: Family caregivers of people with motor neurone disease (MND) experience adverse health outcomes as a result of their caregiving experience. This may be alleviated if their support needs are identified and addressed in a systematic and timely manner. The objective of this pilot study was to assess the feasibility and relevance of the Carers' Alert Thermometer (CAT) in home-based care, from the perspective of MND family caregivers. The tool provides a formal structure to facilitate discussions with caregivers to enable needs to be addressed.

METHODS: This mixed-method study was conducted in Western Australia (2020-2021). Forty-one caregivers and five MND Advisors participated in trialling the CAT intervention which consisted of two encounters with Advisors (6-8 weeks apart) to identify and address support needs through action plans. Caregivers' feedback was obtained via telephone interviews and a thematic analysis was undertaken.

RESULTS: Thirty caregivers completed two CAT assessments. Caregivers identified support priorities of managing their feelings and worries, providing emotional or spiritual care, information about the person's condition and how their care needs might change. Seventeen caregivers were interviewed and found that this assessment process adequately addressed their needs and it should be continued, it brought the focus onto them to clarify problems and work through solutions. The improvements that were suggested by them, including better information/education in palliative care, led to the development of an online support/information toolkit, which served to empower caregivers and staff by accessing relevant information and resources.

CONCLUSIONS: The CAT demonstrated utility for triaging caregivers most in need of additional support and those whom signposting to additional information and self-directed access to support was most appropriate. For any tool to become an integrated part of care, service provider support is key for implementation, allowing for the time resource required and an appropriate education and support structure. MND Associations have an important role in building stronger partnerships with supportive community networks, through compassionate communities models of care, to address the identified needs of MND families in a more sustainable and wholistic manner. Needs assessment is a means towards building this capacity between formal and informal networks.}, } @article {pmid38347806, year = {2024}, author = {Lao, Z and Tang, Y and Dong, X and Tan, Y and Li, X and Liu, X and Li, L and Guo, C and Wei, G}, title = {Elucidating the reversible and irreversible self-assembly mechanisms of low-complexity aromatic-rich kinked peptides and steric zipper peptides.}, journal = {Nanoscale}, volume = {16}, number = {8}, pages = {4025-4038}, doi = {10.1039/d3nr05130g}, pmid = {38347806}, issn = {2040-3372}, mesh = {Protein Conformation ; *Amyloid/chemistry ; *Peptides/chemistry ; Molecular Dynamics Simulation ; Protein Conformation, beta-Strand ; }, abstract = {Many RNA-binding proteins such as fused-in sarcoma (FUS) can self-assemble into reversible liquid droplets and fibrils through the self-association of their low-complexity (LC) domains. Recent experiments have revealed that SYG-rich segments in the FUS LC domains play critical roles in the reversible self-assembly behaviors of FUS. These FUS LC segments alone can self-assemble into reversible kinked fibrils, which are markedly different from the canonical irreversible steric zipper β-sheet fibrils. However, the molecular determinants underlying the reversible and irreversible self-assembly are poorly understood. Herein we conducted extensive all-atom and coarse-grained molecular dynamics simulations of four representative hexapeptides: two low-complexity aromatic-rich kinked peptides from the amyotrophic lateral sclerosis-related FUS protein, FUS37-42 (SYSGYS) and FUS54-59 (SYSSYG); and two steric zipper peptides from Alzheimer's-associated Aβ and Tau proteins, Aβ16-21 (KLVFFA) and Tau306-311 (VQIVYK). We dissected their reversible and irreversible self-assembly dynamics, predicted their phase separation behaviors, and elucidated the underpinning molecular interactions. Our simulations showed that alternating stickers (Tyr) and spacers (Gly and Ser) in FUS37-42 and FUS54-59 facilitate the formation of highly dynamic coil-rich oligomers and lead to reversible self-assembly, while consecutive hydrophobic residues of LVFF in Aβ16-21 and IVY in Tau306-311 act as hydrophobic patches, favoring the formation of stable β-sheet-rich oligomers and driving the irreversible self-assembly. Intriguingly, we found that FUS37-42 and FUS54-59 peptides, possessing the same amino acid composition and the same number of sticker and spacer residues, display differential self-assembly propensities. This finding suggests that the self-assembly behaviors of FUS peptides are fine-tuned by the site-specific patterning of spacer residues (Ser and Gly). This study provides significant mechanistic insights into reversible and irreversible peptide self-assembly, which would be helpful for understanding the molecular mechanisms underlying the formation of biological liquid condensates and pathological solid amyloid fibrils.}, } @article {pmid38347638, year = {2024}, author = {Li, W and Li, HL and Wang, JZ and Liu, R and Wang, X}, title = {Abnormal protein post-translational modifications induces aggregation and abnormal deposition of protein, mediating neurodegenerative diseases.}, journal = {Cell & bioscience}, volume = {14}, number = {1}, pages = {22}, pmid = {38347638}, issn = {2045-3701}, support = {92049107//National Natural Science Foundation of China/ ; 82071440//National Natural Science Foundation of China/ ; 31929002//National Natural Science Foundation of China/ ; }, abstract = {Protein post-translational modifications (PPTMs) refer to a series of chemical modifications that occur after the synthesis of protein. Proteins undergo different modifications such as phosphorylation, acetylation, ubiquitination, and so on. These modifications can alter the protein's structure, function, and interaction, thereby regulating its biological activity. In neurodegenerative diseases, several proteins undergo abnormal post-translational modifications, which leads to aggregation and abnormal deposition of protein, thus resulting in neuronal death and related diseases. For example, the main pathological features of Alzheimer's disease are the aggregation of beta-amyloid protein and abnormal phosphorylation of tau protein. The abnormal ubiquitination and loss of α-synuclein are related to the onset of Parkinson's disease. Other neurodegenerative diseases such as Huntington's disease, amyotrophic lateral sclerosis, and so on are also connected with abnormal PPTMs. Therefore, studying the abnormal PPTMs in neurodegenerative diseases is critical for understanding the mechanism of these diseases and the development of significant therapeutic strategies. This work reviews the implications of PPTMs in neurodegenerative diseases and discusses the relevant therapeutic strategies.}, } @article {pmid38347315, year = {2024}, author = {Huang, SL and Shen, YL and Peng, WY and Ye, K and Zheng, H}, title = {Edaravone for patients with amyotrophic lateral sclerosis: a systematic review and meta-analysis.}, journal = {Acta neurologica Belgica}, volume = {124}, number = {3}, pages = {895-904}, pmid = {38347315}, issn = {2240-2993}, support = {no. 2021JDTD0007//Sichuan Province Science and Technology Support Program/ ; }, mesh = {*Edaravone/therapeutic use ; Humans ; *Amyotrophic Lateral Sclerosis/drug therapy ; Free Radical Scavengers/therapeutic use ; Randomized Controlled Trials as Topic/methods ; Treatment Outcome ; }, abstract = {BACKGROUND AND OBJECTIVE: The effectiveness and long-term efficacy of edaravone, a recommended treatment for amyotrophic lateral sclerosis (ALS), has not been examined in real-world settings. This study aims to evaluate the effectiveness and long-term efficacy of edaravone.

METHODS: The OVID Medline, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science databases were searched for articles published between January 1, 2000, and May 1, 2023. Two investigators independently screened the retrieved articles for randomized controlled trials (RCTs), cohort studies, or single-arm trials that evaluated the effect of edaravone on amyotrophic lateral sclerosis (ALS). The risk of bias was evaluated using the revised Cochrane Risk-of-Bias (RoB 2.0) tool for randomized controlled trials (RCTs) and the Risk-of-Bias In Non-randomized Studies of Interventions (ROBINS-I) tool for observational studies. The primary outcome was the ALSFRS-R score assessed at month 6, with secondary outcomes including the ALSFRS-R scores evaluated at months 9, 12, and 18, forced vital capacity (FVC), and adverse events. The certainty of evidence was assessed using the GRADE approach.

RESULTS: The analysis included 16 studies with a total of 4828 participants. Among these, four were randomized controlled trials (RCTs) and 12 were observational studies. Of the RCTs, four were rated as having a low risk of bias, while six of the observational studies were rated as having a low risk of bias. Edaravone was associated with slightly slower progression in the reduction of ALSFRS-R score at month 6 compared to placebo (mean difference 1.01, 95%CI -0.87 to 3.09, p = 0.293), as shown by evidence from RCTs. However, observational studies did not show any benefit of adding edaravone to routine practice (mean difference 1.85, 95%CI -2.05 to 5.75, p = 0.352). The change from baseline in ALSFRS-R score was -2.1, -4.04, -7.5, -6.82, and -7.9 at months 3, 6, 9, 12, and 18, respectively. The GRADE assessment indicated moderate certainty for evidence from RCTs, while evidence from observational studies had very low certainty.

CONCLUSION: Due to the limited number of studies and confounding issues in observational studies, further examination of the added benefits of edaravone to routine practice is necessary through RCTs, particularly regarding its long-term efficacy.}, } @article {pmid38345477, year = {2024}, author = {Zhu, H and Dalvi, U and Cazenave, W and Cattaert, D and Branchereau, P}, title = {Excitatory action of low frequency depolarizing GABA/glycine synaptic inputs is prevalent in prenatal spinal SOD1[G93A] motoneurons.}, journal = {The Journal of physiology}, volume = {602}, number = {5}, pages = {913-932}, doi = {10.1113/JP285105}, pmid = {38345477}, issn = {1469-7793}, support = {AAP2018//Association pour la Recherche sur la Sclérose Latérale Amyotrophique et autres Maladies du Motoneurone/ ; 23185//AFM-TELETHON/ ; }, mesh = {Mice ; Animals ; *Amyotrophic Lateral Sclerosis ; Glycine/pharmacology ; Superoxide Dismutase-1/genetics ; Spinal Cord/physiology ; Chlorides ; *Neurodegenerative Diseases ; Mice, Transgenic ; Motor Neurons/physiology ; gamma-Aminobutyric Acid/pharmacology ; Disease Models, Animal ; Superoxide Dismutase/genetics ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal adult-onset neurodegenerative disease characterized by progressive motor neuron degeneration and muscle paralysis. Recent evidence suggests the dysfunction of inhibitory signalling in ALS motor neurons. We have shown that embryonic day (E)17.5 spinal motoneurons (MNs) of the SOD1[G93A] mouse model of ALS exhibit an altered chloride homeostasis. At this prenatal stage, inhibition of spinal motoneurons (MNs) is mediated by depolarizing GABAergic/glycinergic postsynaptic potentials (dGPSPs). Here, using an ex vivo preparation and patch clamp recording from MNs with a chloride equilibrium set below spike threshold, we report that low input resistance (Rin) E17.5 MNs from the SOD1[G93A] ALS mouse model do not correctly integrate dGPSPs evoked by electrical stimulations of GABA/glycine inputs at different frequencies. Indeed, firing activity of most wild-type (WT) MNs with low Rin was inhibited by incoming dGPSPs, whereas low Rin SOD1[G93A] MNs were excited or exhibited a dual response (excited by low frequency dGPSPs and inhibited by high frequency dGPSPs). Simulation highlighted the importance of the GABA/glycine input density and showed that pure excitation could be obtained in SOD-like MNs by moving GABA/glycine input away from the cell body to dendrites. This was in agreement with confocal imaging showing a lack of peri-somatic inhibitory terminals in SOD1[G93A] MNs compared to WT littermates. Putative fast ALS-vulnerable MNs with low Rin are therefore lacking functional inhibition at the near-term prenatal stage. KEY POINTS: We analysed the integration of GABAergic/glycinergic synaptic events by embryonic spinal motoneurons (MNs) in a mouse model of the amyotrophic lateral sclerosis (ALS) neurodegenerative disease. We found that GABAergic/glycinergic synaptic events do not properly inhibit ALS MNs with low input resistance, most probably corresponding to future vulnerable MNs. We used a neuron model to highlight the importance of the GABA/glycine terminal location and density in the integration of the GABAergic/glycinergic synaptic events. Confocal imaging showed a lack of GABA/glycine terminals on the cell body of ALS MNs. The present study suggests that putative ALS vulnerable MNs with low Rin lack functional inhibition at the near-term stage.}, } @article {pmid38343852, year = {2024}, author = {Mitra, J and Dharmalingam, P and Kodavati, M and Guerrero, EN and Rao, KS and Garruto, RM and Hegde, ML}, title = {Endogenous TDP-43 mislocalization in a novel knock-in mouse model reveals DNA repair impairment, inflammation, and neuronal senescence.}, journal = {Research square}, volume = {}, number = {}, pages = {}, pmid = {38343852}, issn = {2693-5015}, support = {R01 NS088645/NS/NINDS NIH HHS/United States ; R03 AG064266/AG/NIA NIH HHS/United States ; RF1 NS112719/NS/NINDS NIH HHS/United States ; }, abstract = {TDP-43 mislocalization and aggregation are key pathological features of motor neuron diseases (MND) including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). However, transgenic hTDP-43 WT or ΔNLS-overexpression animal models mainly capture late-stages TDP-43 proteinopathy, and do not provide a complete understanding of early motor neuron-specific pathology during pre-symptomatic phases. We have now addressed this shortcoming by generating a new endogenous knock-in (KI) mouse model using a combination of CRISPR/Cas9 and FLEX Cre-switch strategy for the conditional expression of a mislocalized Tdp-43ΔNLS variant of mouse Tdp-43. This variant is either expressed conditionally in whole mice or specifically in the motor neurons. The mice exhibit loss of nuclear Tdp-43 concomitant with its cytosolic accumulation and aggregation in targeted cells, leading to increased DNA double-strand breaks (DSBs), signs of inflammation and DNA damage-associated cellular senescence. Notably, unlike WT Tdp43 which functionally interacts with Xrcc4 and DNA Ligase 4, the key DSB repair proteins in the non-homologous end-joining (NHEJ) pathway, the Tdp-43ΔNLS mutant sequesters them into cytosolic aggregates, exacerbating neuronal damage in mice brain. The mutant mice also exhibit myogenic degeneration in limb muscles and distinct motor deficits, consistent with the characteristics of MND. Our findings reveal progressive degenerative mechanisms in motor neurons expressing endogenous Tdp-43ΔNLS mutant, independent of TDP-43 overexpression or other confounding etiological factors. Thus, this unique Tdp-43 KI mouse model, which displays key molecular and phenotypic features of Tdp-43 proteinopathy, offers a significant opportunity to further characterize the early-stage progression of MND and also opens avenues for developing DNA repair-targeted approaches for treating TDP-43 pathology-linked neurodegenerative diseases.}, } @article {pmid38343836, year = {2024}, author = {Hobson, R and Levy, SHS and Flaherty, D and Xiao, H and Ciener, B and Reddy, H and Singal, C and Kim, CY and Teich, AF and Shneider, NA and Bradshaw, EM and Elyaman, W}, title = {Clonal CD8 T Cells Accumulate in the Leptomeninges and Communicate with Microglia in Human Neurodegeneration.}, journal = {Research square}, volume = {}, number = {}, pages = {}, pmid = {38343836}, issn = {2693-5015}, support = {P30 CA013696/CA/NCI NIH HHS/United States ; R01 AG067581/AG/NIA NIH HHS/United States ; UL1 TR001873/TR/NCATS NIH HHS/United States ; }, abstract = {Murine studies have highlighted a crucial role for immune cells in the meninges in surveilling the central nervous system (CNS) and influencing neuroinflammation. However, how meningeal immunity is altered in human neurodegeneration and its effects on CNS inflammation is understudied. We performed the first single-cell analysis of the transcriptomes and T cell receptor (TCR) repertoire of 104,635 immune cells from 55 postmortem human brain and leptomeningeal tissues from donors with neurodegenerative diseases including amyotrophic lateral sclerosis, Alzheimer's disease, and Parkinson's disease. RNA and TCR sequencing from paired leptomeninges and brain allowed us to perform lineage tracing to identify the spatial trajectory of clonal T cells in the CNS and its borders. We propose that T cells activated in the brain emigrate to and establish residency in the leptomeninges where they likely contribute to impairments in lymphatic drainage and remotely to CNS inflammation by producing IFNγ and other cytokines. We identified regulatory networks local to the meninges including NK cell-mediated CD8 T cell killing which likely help to control meningeal inflammation. Collectively, these findings provide not only a foundation for future studies into brain border immune surveillance but also highlight important intercellular dynamics that could be leveraged to modulate neuroinflammation.}, } @article {pmid38343431, year = {2024}, author = {Olesen, LK and la Cour, K and Nimmon, L and With, H and Handberg, C}, title = {Experiences of an Online Palliative Rehabilitation Programme for Spousal Caregivers of People With Amyotrophic Lateral Sclerosis and Cognitive and/or Behavioural Impairments: A Qualitative Interpretive Study.}, journal = {Advances in rehabilitation science and practice}, volume = {13}, number = {}, pages = {27536351241227860}, pmid = {38343431}, issn = {2753-6351}, abstract = {PURPOSE: The purpose of this study was to understand how spousal caregivers of people with amyotrophic lateral sclerosis and cognitive and/or behavioural impairments felt about the EMBRACE intervention.

MATERIALS AND METHODS: A qualitative interpretive study, using individual semi-structured interviews pre- and post-participation in a palliative rehabilitation blended learning programme, was applied. In total, 13 spousal caregivers were interviewed pre-intervention and 10 of them post-intervention.

RESULTS: Three overarching themes were identified: Striving to Obtain Control in Everyday Life, Peer support Across the Illness Trajectory and The Complexity of Relations. Information provided in targeted videos and sharing experiences with peers in virtual group meetings were beneficial to comprehend, manage and find meaning in everyday challenges related to being a caregiver.

CONCLUSION: The EMBRACE intervention helped spousal caregivers cope with everyday needs and challenges related to being a caregiver. EMBRACE was found to support and strengthen the participants in gaining more control in everyday life, creating a sense of coherence. Through targeted videos and discussions with peers, the participants felt prepared for the illness trajectory of their relative. Peer support promoted resilient functioning and reduced their feelings of loneliness.

CLINICAL TRIAL REGISTRATION: This study was registered on clinicaltrials.gov under the name: A Complex Intervention Study on a Palliative Rehabilitation Blended Learning Programme to Support Relatives and Health Care Providers of People with ALS and Cognitive Impairments in Coping with Challenges. ID no. NCT04638608. URL: https://clinicaltrials.gov/ct2/results?cond=&term=NCT04638608&cntry=&state=&city=&dist=.}, } @article {pmid38342829, year = {2024}, author = {Bottinelli, C and Baradian, P and Poly, A and Hoizey, G and Chatenay, C}, title = {Identification and quantification of both isomers of hexahydrocannabinol, (9R)-hexahydrocannabinol and (9S)-hexahydrocannabinol, in three different matrices by mass spectrometry.}, journal = {Rapid communications in mass spectrometry : RCM}, volume = {38}, number = {7}, pages = {e9711}, doi = {10.1002/rcm.9711}, pmid = {38342829}, issn = {1097-0231}, mesh = {Tandem Mass Spectrometry/methods ; Reproducibility of Results ; *Cannabinoids/analysis ; *Cannabidiol/analysis ; Gas Chromatography-Mass Spectrometry/methods ; Dronabinol ; }, abstract = {CONTEXT: Hexahydrocannabinol (HHC), a compound derived from synthetic production using cannabidiol (CBD) or delta-9-tetrahydrocannabinol (Δ[9] -THC), has gained recent attention due to its presence in seized materials across Europe. Sold legally in various forms, HHC poses potential health risks, particularly as a legal alternative to THC in some countries. Despite its historical description in the 1940s, limited toxicology data, pharmacological understanding, and analytical methods for HHC exist.

METHOD: This study proposes analytical techniques using mass spectrometry to detect, identify, and quantify (9R)-HHC and (9S)-HHC, concurrently with THC and CBD in various matrices, including oral fluid, whole blood, and seized material. Three distinct methods were employed for different matrices: GC/MS for seized material, GC/MS/MS for whole blood, and UHPLC/MS/MS for oral fluid. Methods were validated qualitatively for oral fluid with a FLOQSwab® device and quantitatively in whole blood and seized material according to Peters et al's recommendations and ICH guidelines.

RESULTS: Validated methods were considered reliable in detecting and quantifying HHC isomers in terms of repeatability, reproducibility, and linearity with r[2] systematically >0.992. These methods were applied to authentic cases, including seized materials and biological samples from traffic control (whole blood and oral fluid). In seized materials, (9R)-HHC levels ranged from 2.09% to 8.85% and (9R)-HHC/(9S)-HHC ratios varied from 1.36 to 2.68. In whole blood sample, (9R)-HHC and (9S)-HHC concentrations were, respectively, 2.38 and 1.39 ng/mL. For all analyzed samples, cannabinoids such as THC and CBD were also detected.

CONCLUSION: This research contributes analytical insights into differentiating and simultaneously analyzing (9R)-HHC and (9S)-HHC, using widely applicable mass spectrometric methods. The study emphasizes the need for vigilance among toxicologists, as new semisynthetic cannabinoids continue to emerge in Europe, with potential health implications. The findings underscore the importance of reliable analytical methods for monitoring these compounds in forensic and clinical settings.}, } @article {pmid38340017, year = {2024}, author = {Kim, JS and Park, M and Park, S and Chae, J and Hong, YH and Park, KS and Sung, JJ and Choi, SJ}, title = {Prognosis of amyotrophic lateral sclerosis patients after tracheostomy invasive ventilation in Korea.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {25}, number = {3-4}, pages = {271-281}, doi = {10.1080/21678421.2024.2314064}, pmid = {38340017}, issn = {2167-9223}, mesh = {Humans ; Male ; Middle Aged ; Female ; *Amyotrophic Lateral Sclerosis/diagnosis/epidemiology/surgery ; *Noninvasive Ventilation ; Retrospective Studies ; Tracheostomy ; Prognosis ; Republic of Korea/epidemiology ; }, abstract = {Background: Tracheostomy invasive ventilation (TIV) is applied to a subset of amyotrophic lateral sclerosis (ALS) patients; however, its frequency and impact on prognosis vary across countries. Methods: We conducted a nationwide retrospective cohort study using Korean National Health Insurance claims data. All patients diagnosed with sporadic ALS from 2012 to 2017 were included, with the observation period until 2020. The survival time between the TIV and non-TIV groups was compared using propensity score matching analysis, and prognostic factors were assessed within the TIV group. Results: This study included 3484 ALS patients (mean [standard deviation] age, 62.4 [11.9] years, 60.4% male), among whom 1230 (35.3%) underwent TIV. After 1:1 propensity score matching, the survival duration between the two groups was not significantly different (28 vs. 25 months, p = 0.057). Cox regression indicated that older age (hazard ratios [HRs] for each decade compared to <40 years: 3.89, 3.83, 5.30, 6.78, and 8.40 [≥80 years]; p < 0.005 for all) and lower income (HR, 1.28; 95% confidence interval [CI], 1.09-1.52; p = 0.003) negatively impacted survival, while gastrostomy (HR, 0.57; 95% CI, 0.50-0.66; p < 0.001) and supportive care services (HR, 0.43; 95% CI, 0.32-0.59; p < 0.001) were associated with prolonged survival. Conclusions: TIV was administered to more than one-third of Korean ALS patients without significant survival prolongation. Older age, lower income, lack of gastrostomy, and insufficient supportive care were independent poor prognostic factors for survival, underscoring the importance of comprehensive management for ALS patients.}, } @article {pmid38339149, year = {2024}, author = {Lee, A and Henderson, R and Aylward, J and McCombe, P}, title = {Gut Symptoms, Gut Dysbiosis and Gut-Derived Toxins in ALS.}, journal = {International journal of molecular sciences}, volume = {25}, number = {3}, pages = {}, pmid = {38339149}, issn = {1422-0067}, support = {There were no grant numbers//Wesley Medical Research/ ; There were no grant numbers//MND Research Australia/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/etiology ; Dysbiosis/etiology ; *Gastrointestinal Microbiome/physiology ; Brain ; }, abstract = {Many pathogenetic mechanisms have been proposed for amyotrophic lateral sclerosis (ALS). Recently, there have been emerging suggestions of a possible role for the gut microbiota. Gut microbiota have a range of functions and could influence ALS by several mechanisms. Here, we review the possible role of gut-derived neurotoxins/excitotoxins. We review the evidence of gut symptoms and gut dysbiosis in ALS. We then examine a possible role for gut-derived toxins by reviewing the evidence that these molecules are toxic to the central nervous system, evidence of their association with ALS, the existence of biochemical pathways by which these molecules could be produced by the gut microbiota and existence of mechanisms of transport from the gut to the blood and brain. We then present evidence that there are increased levels of these toxins in the blood of some ALS patients. We review the effects of therapies that attempt to alter the gut microbiota or ameliorate the biochemical effects of gut toxins. It is possible that gut dysbiosis contributes to elevated levels of toxins and that these could potentially contribute to ALS pathogenesis, but more work is required.}, } @article {pmid38339035, year = {2024}, author = {Sun, Y and Islam, S and Michikawa, M and Zou, K}, title = {Presenilin: A Multi-Functional Molecule in the Pathogenesis of Alzheimer's Disease and Other Neurodegenerative Diseases.}, journal = {International journal of molecular sciences}, volume = {25}, number = {3}, pages = {}, pmid = {38339035}, issn = {1422-0067}, support = {C19K07846//The Grant-in-Aid for Scientific Research/ ; 22K07352//The Ministry of Education, Culture, Sports, Science, and Technology, Japan./ ; JP20dk0207050h0001 and JP20de010702//AMED/ ; no//The 24th General Assembly of the Japanese Association of Medical Sciences/ ; no//Daiko Foundation/ ; no//Hirose International Scholarship Foundation/ ; no//Hori Sciences and Arts Foundation/ ; no//Daiwa Securities Foundation/ ; no//Hirose Foundation/ ; }, mesh = {Humans ; *Alzheimer Disease/metabolism ; Amyloid beta-Peptides/metabolism ; *Neurodegenerative Diseases/etiology ; Amyloid Precursor Protein Secretases/metabolism ; Presenilin-1/genetics/metabolism ; Amyloid beta-Protein Precursor/metabolism ; Apolipoproteins E ; Presenilin-2/genetics/metabolism ; }, abstract = {Presenilin, a transmembrane protein primarily known for its role in Alzheimer's disease (AD) as part of the γ-secretase complex, has garnered increased attention due to its multifaceted functions in various cellular processes. Recent investigations have unveiled a plethora of functions beyond its amyloidogenic role. This review aims to provide a comprehensive overview of presenilin's diverse roles in AD and other neurodegenerative disorders. It includes a summary of well-known substrates of presenilin, such as its involvement in amyloid precursor protein (APP) processing and Notch signaling, along with other functions. Additionally, it highlights newly discovered functions, such as trafficking function, regulation of ferritin expression, apolipoprotein E (ApoE) secretion, the interaction of ApoE and presenilin, and the Aβ42-to-Aβ40-converting activity of ACE. This updated perspective underscores the evolving landscape of presenilin research, emphasizing its broader impact beyond established pathways. The incorporation of these novel findings accentuates the dynamic nature of presenilin's involvement in cellular processes, further advancing our comprehension of its multifaceted roles in neurodegenerative disorders. By synthesizing evidence from a range of studies, this review sheds light on the intricate web of presenilin functions and their implications in health and disease.}, } @article {pmid38339026, year = {2024}, author = {Potenza, RL and Armida, M and Popoli, P}, title = {Can Some Anticancer Drugs Be Repurposed to Treat Amyotrophic Lateral Sclerosis? A Brief Narrative Review.}, journal = {International journal of molecular sciences}, volume = {25}, number = {3}, pages = {}, pmid = {38339026}, issn = {1422-0067}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy ; *Motor Neuron Disease ; *Antineoplastic Agents/pharmacology/therapeutic use ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a rare progressive motor neuron disease that, due to its high complexity, still lacks effective treatments. Development of a new drug is a highly costly and time-consuming process, and the repositioning of approved drugs can represent an efficient strategy to provide therapeutic opportunities. This is particularly true for rare diseases, which are characterised by small patient populations and therefore attract little commercial interest. Based on the overlap between the biological background of cancer and neurodegeneration, the repurposing of antineoplastic drugs for ALS has been suggested. The objective of this narrative review was to summarise the current experimental evidence on the use of approved anticancer drugs in ALS. Specifically, anticancer drugs belonging to different classes were found to act on mechanisms involved in the ALS pathogenesis, and some of them proved to exert beneficial effects in ALS models. However, additional studies are necessary to confirm the real therapeutic potential of anticancer drugs for repositioning in ALS treatment.}, } @article {pmid38338912, year = {2024}, author = {Duranti, E and Cordani, N and Villa, C}, title = {Edaravone: A Novel Possible Drug for Cancer Treatment?.}, journal = {International journal of molecular sciences}, volume = {25}, number = {3}, pages = {}, pmid = {38338912}, issn = {1422-0067}, mesh = {Humans ; Edaravone/therapeutic use ; *Neuroprotective Agents/pharmacology ; *Amyotrophic Lateral Sclerosis/drug therapy ; Antioxidants/therapeutic use ; *Neoplasms/drug therapy/chemically induced ; Free Radical Scavengers/pharmacology ; }, abstract = {Despite significant advancements in understanding the causes and progression of tumors, cancer remains one of the leading causes of death worldwide. In light of advances in cancer therapy, there has been a growing interest in drug repurposing, which involves exploring new uses for medications that are already approved for clinical use. One such medication is edaravone, which is currently used to manage patients with cerebral infarction and amyotrophic lateral sclerosis. Due to its antioxidant and anti-inflammatory properties, edaravone has also been investigated for its potential activities in treating cancer, notably as an anti-proliferative and cytoprotective drug against side effects induced by traditional cancer therapies. This comprehensive review aims to provide updates on the various applications of edaravone in cancer therapy. It explores its potential as a standalone antitumor drug, either used alone or in combination with other medications, as well as its role as an adjuvant to mitigate the side effects of conventional anticancer treatments.}, } @article {pmid38338857, year = {2024}, author = {Venegas, S and Alarcón, C and Araya, J and Gatica, M and Morin, V and Tarifeño-Saldivia, E and Uribe, E}, title = {Biodegradation of Polystyrene by Galleria mellonella: Identification of Potential Enzymes Involved in the Degradative Pathway.}, journal = {International journal of molecular sciences}, volume = {25}, number = {3}, pages = {}, pmid = {38338857}, issn = {1422-0067}, support = {VRID 220.037.026-M//University of Concepción/ ; }, mesh = {Animals ; *Polystyrenes/metabolism ; Chromatography, Liquid ; Proteomics ; Tandem Mass Spectrometry ; *Moths/microbiology ; Larva/metabolism ; Biodegradation, Environmental ; }, abstract = {Galleria mellonella is a lepidopteran whose larval stage has shown the ability to degrade polystyrene (PS), one of the most recalcitrant plastics to biodegradation. In the present study, we fed G. mellonella larvae with PS for 54 days and determined candidate enzymes for its degradation. We first confirmed the biodegradation of PS by Fourier transform infrared spectroscopy- Attenuated total reflectance (FTIR-ATR) and then identified candidate enzymes in the larval gut by proteomic analysis using liquid chromatography with tandem mass spectrometry (LC-MS/MS). Two of these proteins have structural similarities to the styrene-degrading enzymes described so far. In addition, potential hydrolases, isomerases, dehydrogenases, and oxidases were identified that show little similarity to the bacterial enzymes that degrade styrene. However, their response to a diet based solely on polystyrene makes them interesting candidates as a potential new group of polystyrene-metabolizing enzymes in eukaryotes.}, } @article {pmid38338823, year = {2024}, author = {Moreno-Martinez, L and Macías-Redondo, S and Strunk, M and Guillén-Antonini, MI and Lunetta, C and Tarlarini, C and Penco, S and Calvo, AC and Osta, R and Schoorlemmer, J}, title = {New Insights into Endogenous Retrovirus-K Transcripts in Amyotrophic Lateral Sclerosis.}, journal = {International journal of molecular sciences}, volume = {25}, number = {3}, pages = {}, pmid = {38338823}, issn = {1422-0067}, support = {Ayuda de Colegios de Farmacéuticos//Fundación Mehuer, Sevilla, Spain/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism ; *Endogenous Retroviruses/genetics ; Leukocytes, Mononuclear/metabolism ; Brain/metabolism ; Brain Stem/metabolism ; }, abstract = {Retroviral reverse transcriptase activity and the increased expression of human endogenous retroviruses (HERVs) are associated with amyotrophic lateral sclerosis (ALS). We were interested in confirming HERVK overexpression in the ALS brain, its use as an accessory diagnostic marker for ALS, and its potential interplay with neuroinflammation. Using qPCR to analyze HERVK expression in peripheral blood mononuclear cells (PBMCs) and in postmortem brain samples from ALS patients, no significant differences were observed between patients and control subjects. By contrast, we report alterations in the expression patterns of specific HERVK copies, especially in the brainstem. Out of 27 HERVK copies sampled, the relative expression of 17 loci was >1.2-fold changed in samples from ALS patients. In particular, the relative expression of two HERVK copies (Chr3-3 and Chr3-5) was significantly different in brainstem samples from ALS patients compared with controls. Further qPCR analysis of inflammation markers in brain samples revealed a significant increase in NLRP3 levels, while TNFA, IL6, and GZMB showed slight decreases. We cannot confirm global HERVK overexpression in ALS, but we can report the ALS-specific overexpression of selected HERVK copies in the ALS brain. Our data are compatible with the requirement for better patient stratification and support the potential importance of particular HERVK copies in ALS.}, } @article {pmid38337635, year = {2024}, author = {Carrera-Juliá, S and Estrela, JM and Zacarés, M and Navarro, MÁ and Vega-Bello, MJ and de la Rubia Ortí, JE and Moreno, ML and Drehmer, E}, title = {Nutritional, Clinical and Sociodemographic Profiles of Spanish Patients with Amyotrophic Lateral Sclerosis.}, journal = {Nutrients}, volume = {16}, number = {3}, pages = {}, pmid = {38337635}, issn = {2072-6643}, support = {2017-216-001//Valencia Catholic University Saint Vincent Martyr/ ; OTR2017-18255INVES//University of Valencia/ ; }, mesh = {Male ; Female ; Humans ; *Amyotrophic Lateral Sclerosis/epidemiology ; Energy Intake ; Cross-Sectional Studies ; *Neurodegenerative Diseases ; Nutritional Status ; Diet/adverse effects ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a chronic and progressive neurodegenerative disease that leads to the loss of motor neurons. The dietary intake of ALS patients is thought to influence the prognosis and progression of the disease. The aim of this study was to examine the nutritional, clinical and sociodemographic characteristics of ALS patients in Spain. A cross-sectional descriptive study with demographics, clinical anamnesis and anthropometric assessment was carried out. Nutritional intake was recorded and compared with dietary reference intakes (DRI). Forty subjects (25 males; 15 females) aged 54.7 ± 10.17 were included in the study. The mean weight and height were 67.99 ± 8.85 kg and 167.83 ± 8.79 cm, respectively. Clinical phenotype, time to diagnosis, year of onset and family history were not associated with the place of origin. Clinical phenotype had no influence on time of diagnosis. Caloric and protein intakes were adequate, while carbohydrate, vitamin B8 and iodine intakes were significantly lower than the DRI. Lipids; vitamins B1, B2, B3, B5, B6, B12, C and E; sodium; phosphorus; and selenium intakes were significantly higher than the recommended nutritional standards. ALS patients, who are homogeneously distributed throughout our national territory, should modify their dietary habits to minimize ultra-processed products and prioritize foods rich in healthy fats and fiber.}, } @article {pmid38337170, year = {2024}, author = {White, S and O'Cathain, A and Halliday, V and Bradburn, M and McDermott, CJ}, title = {Supporting people with Motor Neuron Disease (MND) to make decisions about gastrostomy feeding tube placement: a survey of UK healthcare professionals' practice and beliefs.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {25}, number = {3-4}, pages = {290-298}, pmid = {38337170}, issn = {2167-9223}, mesh = {Humans ; Gastrostomy ; *Amyotrophic Lateral Sclerosis ; Cross-Sectional Studies ; *Motor Neuron Disease/surgery ; United Kingdom ; Delivery of Health Care ; }, abstract = {OBJECTIVE: Understand the practice and beliefs of healthcare professionals (HCPs) supporting the decision-making of people with MND (pwMND) about gastrostomy placement, including identifying differences between professions.

METHODS: An online cross-sectional survey disseminated to HCPs who support the decision-making of pwMND about gastrostomy placement.

RESULTS: A total of 139 participants completed the survey including representation from a range of healthcare professions. A third (36/101, 36%) initiated discussions about gastrostomy later in practice than they believed was ideal. In relation to the outcome of declining compared to accepting gastrostomy, participants were more likely to discuss aspiration (80% vs. 68%), choking (76% vs. 58%) and prognosis (36% vs. 22%). Participants believed gastrostomies should be placed after a mean 8.1% weight loss since symptom-onset. More participants favored gastrostomy placement before pwMND presented with respiratory symptoms (45%) compared to onset of dysphagia (11%). Half believed pwMND placed gastrostomies too late. Participants were more likely to 'often'/'always' recommend pwMND to have a gastrostomy (23%) than continue without (7%) or decline (4%) gastrostomy, when believing these were the best option for pwMND. Nurses and dietitians discussed the broadest range of information, while doctors were more likely to discuss mortality risk and prognosis.

CONCLUSION: There is variation in HCPs practice and beliefs about initiating discussions, the sharing of information and recommendations, and timing, about gastrostomy placement. The information shared varies by profession and there is evidence of sub-optimal communication between HCPs. Further research is required to understand how these findings may impact on the decision-making of pwMND about gastrostomy.}, } @article {pmid38337058, year = {2024}, author = {Choi, BJ and Park, MH and Jin, HK and Bae, JS}, title = {Acid sphingomyelinase as a pathological and therapeutic target in neurological disorders: focus on Alzheimer's disease.}, journal = {Experimental & molecular medicine}, volume = {56}, number = {2}, pages = {301-310}, pmid = {38337058}, issn = {2092-6413}, mesh = {Animals ; Humans ; Mice ; *Alzheimer Disease/drug therapy ; Brain ; *Multiple Sclerosis ; *Nervous System Diseases ; Sphingomyelin Phosphodiesterase/genetics ; }, abstract = {Over the past decade, numerous studies have highlighted the importance of acid sphingomyelinase (ASM) in disease treatment in humans. This enzyme functions primarily to generate ceramide, maintain the cellular membrane, and regulate cellular function. However, in the blood and brain of patients with neurological disorders, including major depression, ischemic stroke, amyotrophic lateral sclerosis, multiple sclerosis, and Alzheimer's disease (AD), elevated ASM levels significantly suggest disease onset or progression. In these diseases, increased ASM is profoundly involved in neuronal death, abnormal autophagy, neuroinflammation, blood-brain barrier disruption, hippocampal neurogenesis loss, and immune cell dysfunction. Moreover, genetic and pharmacological inhibition of ASM can prevent or ameliorate various diseases. The therapeutic effects of ASM inhibition have prompted the urgent need to develop ASM inhibitors, and several ASM inhibitors have been identified. In this review, we summarize the current knowledge on the critical roles and mechanisms of ASM in brain cells and blood that are associated with different neuropathological features, especially those observed in AD. Furthermore, we elucidate the potential possibility and limitations of existing ASM-targeting drugs according to experimental studies in neurological disorder mouse models.}, } @article {pmid38336911, year = {2024}, author = {Menšíková, K and Rosales, R and Colosimo, C and Spencer, P and Lannuzel, A and Ugawa, Y and Sasaki, R and Giménez-Roldán, S and Matej, R and Tuckova, L and Hrabos, D and Kolarikova, K and Vodicka, R and Vrtel, R and Strnad, M and Hlustik, P and Otruba, P and Prochazka, M and Bares, M and Boluda, S and Buee, L and Ransmayr, G and Kaňovský, P}, title = {Reply to: Questioning the cycad theory of Kii ALS-PDC causation.}, journal = {Nature reviews. Neurology}, volume = {20}, number = {3}, pages = {195-196}, pmid = {38336911}, issn = {1759-4766}, mesh = {Humans ; *Parkinsonian Disorders ; *Amyotrophic Lateral Sclerosis/etiology/complications ; }, } @article {pmid38336910, year = {2024}, author = {Kokubo, Y and Morimoto, S and Yoshida, M}, title = {Questioning the cycad theory of Kii ALS-PDC causation.}, journal = {Nature reviews. Neurology}, volume = {20}, number = {3}, pages = {194}, pmid = {38336910}, issn = {1759-4766}, mesh = {Humans ; *Parkinsonian Disorders ; *Amyotrophic Lateral Sclerosis/etiology/complications ; }, } @article {pmid38336286, year = {2024}, author = {Lomeli, N and Pearre, DC and Cruz, M and Di, K and Ricks-Oddie, JL and Bota, DA}, title = {Cisplatin induces BDNF downregulation in middle-aged female rat model while BDNF enhancement attenuates cisplatin neurotoxicity.}, journal = {Experimental neurology}, volume = {375}, number = {}, pages = {114717}, pmid = {38336286}, issn = {1090-2430}, support = {TL1 TR001415/TR/NCATS NIH HHS/United States ; T32 NS082174/NS/NINDS NIH HHS/United States ; R01 CA263806/CA/NCI NIH HHS/United States ; UL1 TR001414/TR/NCATS NIH HHS/United States ; T32 CA060396/CA/NCI NIH HHS/United States ; P30 CA062203/CA/NCI NIH HHS/United States ; K08 NS072234/NS/NINDS NIH HHS/United States ; }, mesh = {Rats ; Animals ; Female ; *Cisplatin/toxicity ; *Brain-Derived Neurotrophic Factor/metabolism ; Rats, Sprague-Dawley ; Down-Regulation ; Quality of Life ; Riluzole/pharmacology ; Hippocampus/metabolism ; Disks Large Homolog 4 Protein ; }, abstract = {Cancer-related cognitive impairments (CRCI) are neurological complications associated with cancer treatment, and greatly affect cancer survivors' quality of life. Brain-derived neurotrophic factor (BDNF) plays an essential role in neurogenesis, learning and memory. The reduction of BDNF is associated with the decrease in cognitive function in various neurological disorders. Few pre-clinical studies have reported on the effects of chemotherapy and medical stress on BDNF levels and cognition. The present study aimed to compare the effects of medical stress and cisplatin on serum BDNF levels and cognitive function in 9-month-old female Sprague Dawley rats to age-matched controls. Serum BDNF levels were collected longitudinally during cisplatin treatment, and cognitive function was assessed by novel object recognition (NOR) 14 weeks post-cisplatin initiation. Terminal BDNF levels were collected 24 weeks after cisplatin initiation. In cultured hippocampal neurons, we screened three neuroprotective agents, riluzole (an approved treatment for amyotrophic lateral sclerosis), as well as the ampakines CX546 and CX1739. We assessed dendritic arborization by Sholl analysis and dendritic spine density by quantifying postsynaptic density-95 (PSD-95) puncta. Cisplatin and exposure to medical stress reduced serum BDNF levels and impaired object discrimination in NOR compared to age-matched controls. Pharmacological BDNF augmentation protected neurons against cisplatin-induced reductions in dendritic branching and PSD-95. Ampakines (CX546 and CX1739) and riluzole did not affect the antitumor efficacy of cisplatin in vitro. In conclusion, we established the first middle-aged rat model of cisplatin-induced CRCI, assessing the contribution of medical stress and longitudinal changes in BDNF levels on cognitive function, although future studies are warranted to assess the efficacy of BDNF enhancement in vivo on synaptic plasticity. Collectively, our results indicate that cancer treatment exerts long-lasting changes in BDNF levels, and support BDNF enhancement as a potential preventative approach to target CRCI with therapeutics that are FDA approved and/or in clinical study for other indications.}, } @article {pmid38336279, year = {2024}, author = {Costa-Pinto, S and Gonçalves-Ribeiro, J and Tedim-Moreira, J and Socodato, R and Relvas, JB and Sebastião, AM and Vaz, SH}, title = {Communication defects with astroglia contribute to early impairments in the motor cortex plasticity of SOD1[G93A] mice.}, journal = {Neurobiology of disease}, volume = {193}, number = {}, pages = {106435}, doi = {10.1016/j.nbd.2024.106435}, pmid = {38336279}, issn = {1095-953X}, mesh = {Mice ; Animals ; Astrocytes/metabolism ; *Amyotrophic Lateral Sclerosis/metabolism ; Superoxide Dismutase-1/genetics/metabolism ; Mice, Transgenic ; *Motor Cortex ; *Neurodegenerative Diseases/metabolism ; Proteomics ; Disease Models, Animal ; Superoxide Dismutase/genetics/metabolism ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease, involving the selective degeneration of cortical upper synapses in the primary motor cortex (M1). Excitotoxicity in ALS occurs due to an imbalance between excitation and inhibition, closely linked to the loss/gain of astrocytic function. Using the ALS SOD1[G93A] mice, we investigated the astrocytic contribution for the electrophysiological alterations observed in the M1 of SOD1[G93A] mice, throughout disease progression. Results showed that astrocytes are involved in synaptic dysfunction observed in presymptomatic SOD1[G93A] mice, since astrocytic glutamate transport currents are diminished and pharmacological inhibition of astrocytes only impaired long-term potentiation and basal transmission in wild-type mice. Proteomic analysis revealed major differences in neuronal transmission, metabolism, and immune system in upper synapses, confirming early communication deficits between neurons and astroglia. These results provide valuable insights into the early impact of upper synapses in ALS and the lack of supportive functions of cortical astrocytes, highlighting the possibility of manipulating astrocytes to improve synaptic function.}, } @article {pmid38335961, year = {2024}, author = {Klickstein, JA and Johnson, MA and Antonoudiou, P and Maguire, J and Paulo, JA and Gygi, SP and Weihl, C and Raman, M}, title = {ALS-related p97 R155H mutation disrupts lysophagy in iPSC-derived motor neurons.}, journal = {Stem cell reports}, volume = {19}, number = {3}, pages = {366-382}, pmid = {38335961}, issn = {2213-6711}, support = {R01 GM127557/GM/NIGMS NIH HHS/United States ; R01 NS102937/NS/NINDS NIH HHS/United States ; P50 MH122379/MH/NIMH NIH HHS/United States ; R01 GM067945/GM/NIGMS NIH HHS/United States ; R01 AA026256/AA/NIAAA NIH HHS/United States ; R01 MH128235/MH/NIMH NIH HHS/United States ; K24 AR073317/AR/NIAMS NIH HHS/United States ; R01 AG031867/AG/NIA NIH HHS/United States ; R21 NS123631/NS/NINDS NIH HHS/United States ; K12 GM133314/GM/NIGMS NIH HHS/United States ; R01 GM132129/GM/NIGMS NIH HHS/United States ; R01 NS105628/NS/NINDS NIH HHS/United States ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics ; *Induced Pluripotent Stem Cells ; Macroautophagy ; Motor Neurons ; Mutation ; }, abstract = {Mutations in the AAA+ ATPase p97 cause multisystem proteinopathy 1, which includes amyotrophic lateral sclerosis; however, the pathogenic mechanisms that contribute to motor neuron loss remain obscure. Here, we use two induced pluripotent stem cell models differentiated into spinal motor neurons to investigate how p97 mutations perturb the motor neuron proteome. Using quantitative proteomics, we find that motor neurons harboring the p97 R155H mutation have deficits in the selective autophagy of lysosomes (lysophagy). p97 R155H motor neurons are unable to clear damaged lysosomes and have reduced viability. Lysosomes in mutant motor neurons have increased pH compared with wild-type cells. The clearance of damaged lysosomes involves UBXD1-p97 interaction, which is disrupted in mutant motor neurons. Finally, inhibition of the ATPase activity of p97 using the inhibitor CB-5083 rescues lysophagy defects in mutant motor neurons. These results add to the evidence that endo-lysosomal dysfunction is a key aspect of disease pathogenesis in p97-related disorders.}, } @article {pmid38295729, year = {2024}, author = {Bhatt, N and Puangmalai, N and Sengupta, U and Jerez, C and Kidd, M and Gandhi, S and Kayed, R}, title = {C9orf72-associated dipeptide protein repeats form A11-positive oligomers in amyotrophic lateral sclerosis and frontotemporal dementia.}, journal = {The Journal of biological chemistry}, volume = {300}, number = {2}, pages = {105628}, pmid = {38295729}, issn = {1083-351X}, support = {R01 AG054025/AG/NIA NIH HHS/United States ; R01 NS094557/NS/NINDS NIH HHS/United States ; R01 AG060718/AG/NIA NIH HHS/United States ; RF1 AG055771/AG/NIA NIH HHS/United States ; }, mesh = {Humans ; *Frontotemporal Dementia/genetics ; *Amyotrophic Lateral Sclerosis/genetics/metabolism ; C9orf72 Protein/genetics/metabolism ; DNA Repeat Expansion ; Dipeptides/chemistry ; Arginine ; Amyloidogenic Proteins ; Glycine ; }, abstract = {Hexanucleotide repeat expansion in C9orf72 is one of the most common causes of amyotrophic lateral sclerosis and frontotemporal dementia. The hexanucleotide expansion, formed by GGGGCC (G4C2) repeats, leads to the production of five dipeptide protein repeats (DPRs) via repeat-associated non-AUG translation. Among the five dipeptide repeats, Gly-Arg, Pro-Arg, and Gly-Ala form neuronal inclusions that contain aggregates of the peptides. Several studies have attempted to model DPR-associated toxicity using various repeat lengths, which suggests a unique conformation that is cytotoxic and is independent of the repeat length. However, the structural characteristics of DPR aggregates have yet to be determined. Increasing evidence suggests that soluble species, such as oligomers, are the main cause of toxicity in proteinopathies, such as Alzheimer's and Parkinson's disease. To investigate the ability of DPRs to aggregate and form toxic oligomers, we adopted a reductionist approach using small dipeptide repeats of 3, 6, and 12. This study shows that DPRs, particularly glycine-arginine and proline-arginine, form oligomers that exhibit distinct dye-binding properties and morphologies. Importantly, we also identified toxic DPR oligomers in amyotrophic lateral sclerosis and frontotemporal dementia postmortem brains that are morphologically similar to those generated recombinantly. This study demonstrates that, similar to soluble oligomers formed by various amyloid proteins, DPR oligomers are toxic, independent of their repeat length.}, } @article {pmid38334818, year = {2024}, author = {Hoek, AG and Dal Canto, E and Wenker, E and Bindraban, N and Handoko, ML and Elders, PJM and Beulens, JWJ}, title = {Epidemiology of heart failure in diabetes: a disease in disguise.}, journal = {Diabetologia}, volume = {67}, number = {4}, pages = {574-601}, pmid = {38334818}, issn = {1432-0428}, support = {91718304/ZONMW_/ZonMw/Netherlands ; }, mesh = {Humans ; *Diabetes Mellitus, Type 2/epidemiology/complications ; *Heart Failure/epidemiology/physiopathology ; Incidence ; Prevalence ; Stroke Volume/physiology ; Ventricular Dysfunction, Left/epidemiology/physiopathology ; Echocardiography ; }, abstract = {Left ventricular diastolic dysfunction (LVDD) without symptoms, and heart failure (HF) with preserved ejection fraction (HFpEF) represent the most common phenotypes of HF in individuals with type 2 diabetes mellitus, and are more common than HF with reduced ejection fraction (HFrEF), HF with mildly reduced ejection fraction (HFmrEF) and left ventricular systolic dysfunction (LVSD) in these individuals. However, diagnostic criteria for HF have changed over the years, resulting in heterogeneity in the prevalence/incidence rates reported in different studies. We aimed to give an overview of the diagnosis and epidemiology of HF in type 2 diabetes, using both a narrative and systematic review approach; we focus narratively on diagnosing (using the 2021 European Society of Cardiology [ESC] guidelines) and screening for HF in type 2 diabetes. We performed an updated (2016-October 2022) systematic review and meta-analysis of studies reporting the prevalence and incidence of HF subtypes in adults ≥18 years with type 2 diabetes, using echocardiographic data. Embase and MEDLINE databases were searched and data were assessed using random-effects meta-analyses, with findings presented as forest plots. From the 5015 studies found, 209 were screened using the full-text article. In total, 57 studies were included, together with 29 studies that were identified in a prior meta-analysis; these studies reported on the prevalence of LVSD (n=25 studies, 24,460 individuals), LVDD (n=65 studies, 25,729 individuals), HFrEF (n=4 studies, 4090 individuals), HFmrEF (n=2 studies, 2442 individuals) and/or HFpEF (n=8 studies, 5292 individuals), and on HF incidence (n=7 studies, 17,935 individuals). Using Hoy et al's risk-of-bias tool, we found that the studies included generally had a high risk of bias. They showed a prevalence of 43% (95% CI 37%, 50%) for LVDD, 17% (95% CI 7%, 35%) for HFpEF, 6% (95% CI 3%, 10%) for LVSD, 7% (95% CI 3%, 15%) for HFrEF, and 12% (95% CI 7%, 22%) for HFmrEF. For LVDD, grade I was found to be most prevalent. Additionally, we reported a higher incidence rate of HFpEF (7% [95% CI 4%, 11%]) than HFrEF 4% [95% CI 3%, 7%]). The evidence is limited by the heterogeneity of the diagnostic criteria over the years. The systematic section of this review provides new insights on the prevalence/incidence of HF in type 2 diabetes, unveiling a large pre-clinical target group with LVDD/HFpEF in which disease progression could be halted by early recognition and treatment.Registration PROSPERO ID CRD42022368035.}, } @article {pmid38334639, year = {2024}, author = {Cunha-Oliveira, T and Montezinho, L and Simões, RF and Carvalho, M and Ferreiro, E and Silva, FSG}, title = {Mitochondria: A Promising Convergent Target for the Treatment of Amyotrophic Lateral Sclerosis.}, journal = {Cells}, volume = {13}, number = {3}, pages = {}, pmid = {38334639}, issn = {2073-4409}, support = {PTDC/MED-FAR/29391/2017//Fundação para a Ciência e Tecnologia/ ; POCI-01-0145-FEDER-029391//Fundação para a Ciência e Tecnologia/ ; PTDC/BTM-SAL/29297/2017//Fundação para a Ciência e Tecnologia/ ; POCI-01-0145-FEDER-029297//Fundação para a Ciência e Tecnologia/ ; PTDC/BTM-ORG/0055/2021//Fundação para a Ciência e Tecnologia/ ; DL57/2016/CP1448/CT0016//Fundação para a Ciência e Tecnologia/ ; CEECIND/00322/2017//Fundação para a Ciência e Tecnologia/ ; 2022.00011.CEECIND//Fundação para a Ciência e Tecnologia/ ; UIDP/04539/2020//Fundação para a Ciência e Tecnologia/ ; UIDB/04539/2020//Fundação para a Ciência e Tecnologia/ ; UIDB/00081/2020//Fundação para a Ciência e Tecnologia/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism ; *Neurodegenerative Diseases/metabolism ; Mitochondria/metabolism ; Motor Neurons/pathology ; Apoptosis ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by the progressive loss of motor neurons, for which current treatment options are limited. Recent studies have shed light on the role of mitochondria in ALS pathogenesis, making them an attractive therapeutic intervention target. This review contains a very comprehensive critical description of the involvement of mitochondria and mitochondria-mediated mechanisms in ALS. The review covers several key areas related to mitochondria in ALS, including impaired mitochondrial function, mitochondrial bioenergetics, reactive oxygen species, metabolic processes and energy metabolism, mitochondrial dynamics, turnover, autophagy and mitophagy, impaired mitochondrial transport, and apoptosis. This review also highlights preclinical and clinical studies that have investigated various mitochondria-targeted therapies for ALS treatment. These include strategies to improve mitochondrial function, such as the use of dichloroacetate, ketogenic and high-fat diets, acetyl-carnitine, and mitochondria-targeted antioxidants. Additionally, antiapoptotic agents, like the mPTP-targeting agents minocycline and rasagiline, are discussed. The paper aims to contribute to the identification of effective mitochondria-targeted therapies for ALS treatment by synthesizing the current understanding of the role of mitochondria in ALS pathogenesis and reviewing potential convergent therapeutic interventions. The complex interplay between mitochondria and the pathogenic mechanisms of ALS holds promise for the development of novel treatment strategies to combat this devastating disease.}, } @article {pmid38334609, year = {2024}, author = {Noori, L and Saqagandomabadi, V and Di Felice, V and David, S and Caruso Bavisotto, C and Bucchieri, F and Cappello, F and Conway de Macario, E and Macario, AJL and Scalia, F}, title = {Putative Roles and Therapeutic Potential of the Chaperone System in Amyotrophic Lateral Sclerosis and Multiple Sclerosis.}, journal = {Cells}, volume = {13}, number = {3}, pages = {}, pmid = {38334609}, issn = {2073-4409}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism ; *Multiple Sclerosis/therapy ; Molecular Chaperones/metabolism ; Heat-Shock Proteins/metabolism ; }, abstract = {The putative pathogenic roles and therapeutic potential of the chaperone system (CS) in amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS) are reviewed to provide a bibliographic and conceptual platform for launching research on the diagnostic and therapeutic applications of CS components. Various studies suggest that dysfunction of the CS contributes to the pathogenesis of ALS and MS, and here, we identify some of the implicated CS members. The physiology and pathophysiology of the CS members can be properly understood if they are studied or experimentally or clinically manipulated for diagnostic or therapeutic purposes, bearing in mind that they belong to a physiological system with multiple interacting and dynamic components, widespread throughout the body, intra- and extracellularly. Molecular chaperones, some called heat shock protein (Hsp), are the chief components of the CS, whose canonical functions are cytoprotective. However, abnormal chaperones can be etiopathogenic factors in a wide range of disorders, chaperonopathies, including ALS and MS, according to the data reviewed. Chaperones typically form teams, and these build functional networks to maintain protein homeostasis, the canonical role of the CS. However, members of the CS also display non-canonical functions unrelated to protein homeostasis. Therefore, chaperones and other members of the CS, if abnormal, may disturb not only protein synthesis, maturation, and migration but also other physiological processes. Thus, in elucidating the role of CS components in ALS and MS, one must look at protein homeostasis abnormalities and beyond, following the clues emerging from the works discussed here.}, } @article {pmid38334356, year = {2024}, author = {Kleinveld, VEA and Keritam, O and Horlings, CGC and Cetin, H and Wanschitz, J and Hotter, A and Zirch, LS and Zimprich, F and Topakian, R and Müller, P and Oel, D and Quasthoff, S and Erdler, M and Rauschka, H and Grinzinger, S and Jecel, J and Gaulhofer, P and Castek, B and Stadler, K and Löscher, WN}, title = {Multifocal motor neuropathy as a mimic of amyotrophic lateral sclerosis: Serum neurofilament light chain as a reliable diagnostic biomarker.}, journal = {Muscle & nerve}, volume = {69}, number = {4}, pages = {422-427}, doi = {10.1002/mus.28054}, pmid = {38334356}, issn = {1097-4598}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis ; Biomarkers ; Intermediate Filaments ; Prognosis ; *Polyneuropathies/diagnosis ; Neurofilament Proteins ; }, abstract = {INTRODUCTION/AIMS: The clinical presentation of multifocal motor neuropathy (MMN) may mimic early amyotrophic lateral sclerosis (ALS) with predominant lower motor neuron (LMN) involvement, posing a diagnostic challenge. Both diseases have specific treatments and prognoses, highlighting the importance of early diagnosis. The aim of this study was to assess the diagnostic value of serum neurofilament light chain (NfL) in differentiating MMN from LMN dominant ALS.

METHODS: NfL was measured in serum in n = 37 patients with MMN and n = 37 age- and sex-matched patients with LMN dominant ALS, to determine the diagnostic accuracy. Clinical and demographic data were obtained at the time of NfL sampling.

RESULTS: Serum NfL concentration was significantly lower in MMN patients compared to ALS patients (mean 20.7 pg/mL vs. 59.4 pg/mL, p < .01). NfL demonstrated good diagnostic value in discriminating the two groups (AUC 0.985 [95% CI 0.963-1.000], sensitivity 94.6%, specificity 100%, cut-off 44.00 pg/mL).

DISCUSSION: NfL could be a helpful tool in differentiating MMN from LMN dominant ALS in those patients in whom electrophysiological and clinical examinations remain inconclusive early in the diagnostic process.}, } @article {pmid38334254, year = {2024}, author = {Mohammadi, S and Ghaderi, S and Fatehi, F}, title = {MRI biomarkers and neuropsychological assessments of hippocampal and parahippocampal regions affected by ALS: A systematic review.}, journal = {CNS neuroscience & therapeutics}, volume = {30}, number = {2}, pages = {e14578}, pmid = {38334254}, issn = {1755-5949}, mesh = {Humans ; *Hippocampus/diagnostic imaging/pathology ; *Amyotrophic Lateral Sclerosis/diagnostic imaging/psychology/pathology/metabolism ; *Magnetic Resonance Imaging ; *Neuropsychological Tests ; *Biomarkers/metabolism ; Parahippocampal Gyrus/diagnostic imaging/pathology ; }, abstract = {BACKGROUND AND OBJECTIVE: Amyotrophic lateral sclerosis (ALS) is a progressive motor and extra-motor neurodegenerative disease. This systematic review aimed to examine MRI biomarkers and neuropsychological assessments of the hippocampal and parahippocampal regions in patients with ALS.

METHODS: A systematic review was conducted in the Scopus and PubMed databases for studies published between January 2000 and July 2023. The inclusion criteria were (1) MRI studies to assess hippocampal and parahippocampal regions in ALS patients, and (2) studies reporting neuropsychological data in patients with ALS.

RESULTS: A total of 46 studies were included. Structural MRI revealed hippocampal atrophy, especially in ALS-FTD, involving specific subregions (CA1, dentate gyrus). Disease progression and genetic factors impacted atrophy patterns. Diffusion tensor imaging (DTI) showed increased mean diffusivity (MD), axial diffusivity (AD), radial diffusivity (RD), and decreased fractional anisotropy (FA) in the hippocampal tracts and adjacent regions, indicating loss of neuronal and white matter integrity. Functional MRI (fMRI) revealed reduced functional connectivity (FC) between the hippocampus, parahippocampus, and other regions, suggesting disrupted networks. Perfusion MRI showed hypoperfusion in parahippocampal gyri. Magnetic resonance spectroscopy (MRS) found changes in the hippocampus, indicating neuronal loss. Neuropsychological tests showed associations between poorer memory and hippocampal atrophy or connectivity changes. CA1-2, dentate gyrus, and fimbria atrophy were correlated with worse memory.

CONCLUSIONS: The hippocampus and the connected regions are involved in ALS. Hippocampal atrophy disrupted connectivity and metabolite changes correlate with cognitive and functional decline. Specific subregions can be particularly affected. The hippocampus is a potential biomarker for disease monitoring and prognosis.}, } @article {pmid38334027, year = {2024}, author = {Cao, YB and Wu, Y and Dong, QY and Huang, NX and Zou, ZY and Chen, HJ}, title = {Neurite orientation dispersion and density imaging quantifies microstructural impairment in the thalamus and its connectivity in amyotrophic lateral sclerosis.}, journal = {CNS neuroscience & therapeutics}, volume = {30}, number = {2}, pages = {e14616}, pmid = {38334027}, issn = {1755-5949}, support = {2022QNA022//Fujian Provincial Health Technology Project/ ; 2023CXA009//Fujian Provincial Health Technology Project/ ; 62201265//National Natural Science Foundation of China/ ; }, mesh = {Humans ; *Neurites ; Diffusion Tensor Imaging/methods ; *Amyotrophic Lateral Sclerosis/diagnostic imaging ; Thalamus/diagnostic imaging ; Neural Pathways/diagnostic imaging ; }, abstract = {AIMS: To evaluate microstructural impairment in the thalamus and thalamocortical connectivity using neurite orientation dispersion and density imaging (NODDI) in amyotrophic lateral sclerosis (ALS).

METHODS: This study included 47 healthy controls and 43 ALS patients, whose structural and diffusion-weighted data were collected. We used state-of-the-art parallel transport tractography to identify thalamocortical pathways in individual spaces. Thalamus was then parcellated into six subregions based on its connectivity pattern with the priori defined cortical (i.e., prefrontal/motor/somatosensory/temporal/posterior-parietal/occipital) regions. For each of the thalamic and cortical subregions and thalamo-cortical tracts, we compared the following NODDI metrics between groups: orientation dispersion index (ODI), neurite density index (NDI), and isotropic volume fraction (ISO). We also used these metrics to conduct receiver operating characteristic curve (ROC) analyses and Spearman correlation.

RESULTS: In ALS patients, we found decreased ODI and increased ISO in the thalamic subregion connecting the left motor cortex and other extramotor (e.g., somatosensory and occipital) cortex (Bonferroni-corrected p < 0.05). NDI decreased in the bilateral thalamo-motor and thalamo-somatosensory tracts and in the right thalamo-posterior-parietal and thalamo-occipital tracts (Bonferroni-corrected p < 0.05). NDI reduction in the bilateral thalamo-motor tract (p = 0.017 and 0.009) and left thalamo-somatosensory tract (p = 0.029) was correlated with disease severity. In thalamo-cortical tracts, NDI yielded a higher effect size during between-group comparisons and a greater area under ROC (p < 0.05) compared with conventional diffusion tensor imaging metrics.

CONCLUSIONS: Microstructural impairment in the thalamus and thalamocortical connectivity is the hallmark of ALS. NODDI improved the detection of disrupted thalamo-cortical connectivity in ALS.}, } @article {pmid38332900, year = {2024}, author = {Du, L and Pang, Y}, title = {Identifying Regenerated Saplings by Stratifying Forest Overstory Using Airborne LiDAR Data.}, journal = {Plant phenomics (Washington, D.C.)}, volume = {6}, number = {}, pages = {0145}, pmid = {38332900}, issn = {2643-6515}, abstract = {Identifying the spatiotemporal distributions and phenotypic characteristics of understory saplings is beneficial in exploring the internal mechanisms of plant regeneration and providing technical assistances for continues cover forest management. However, it is challenging to detect the understory saplings using 2-dimensional (2D) spectral information produced by conventional optical remotely sensed data. This study proposed an automatic method to detect the regenerated understory saplings based on the 3D structural information from aerial laser scanning (ALS) data. By delineating individual tree crown using the improved spectral clustering algorithm, we successfully removed the overstory canopy and associated trunk points. Then, individual understory saplings were segmented using an adaptive-mean-shift-based clustering algorithm. This method was tested in an experimental forest farm of North China. Our results showed that the detection rates of understory saplings ranged from 94.41% to 152.78%, and the matching rates increased from 62.59% to 95.65% as canopy closure went down. The ALS-based sapling heights well captured the variations of field measurements [R[2] = 0.71, N = 3,241, root mean square error (RMSE) = 0.26 m, P < 0.01] and terrestrial laser scanning (TLS)-based measurements (R[2] = 0.78, N =443, RMSE = 0.23 m, P < 0.01). The ALS-based sapling crown width was comparable with TLS-based measurements (R[2] = 0.64, N = 443, RMSE = 0.24 m). This study provides a solution for the quantification of understory saplings, which can be used to improve forest ecosystem resilence through regulating the dynamics of forest gaps to better utilize light resources.}, } @article {pmid38332698, year = {2024}, author = {Sung, JH and Baek, SH and Park, JW and Lee, JH and Son, MH and Kim, BJ}, title = {Dynamic suprahyoid muscle ultrasound in assessing oropharyngeal dysphagia in neurological disorders.}, journal = {European journal of physical and rehabilitation medicine}, volume = {60}, number = {2}, pages = {233-244}, pmid = {38332698}, issn = {1973-9095}, mesh = {Humans ; *Deglutition Disorders/diagnostic imaging/etiology ; Cross-Sectional Studies ; Deglutition/physiology ; *Stroke/complications/diagnostic imaging ; Ultrasonography ; Muscles ; }, abstract = {BACKGROUND: Appropriate evaluation and management of dysphagia are essential in neurological disorders. However, there is currently a lack of a simple yet reliable method for dysphagia evaluation.

AIM: This study aimed to investigate the usefulness of new dynamic M-mode ultrasonography (US) parameters of suprahyoid muscle (SHM) to evaluate dysphagia.

DESIGN: Prospective observational, cross-sectional study.

SETTING: Inpatient setting at neurology department of tertiary medical center.

POPULATION: A total of 89 patients with dysphagia and 175 healthy volunteers were enrolled in the study. Patients were subdivided into mild and severe dysphagia groups depending on the need for dietary changes and disease classification, which included amyotrophic lateral sclerosis, peripheral neuromuscular diseases, and stroke.

METHODS: Dynamic M-mode US was performed during swallowing to obtain the SHM thickness (the baseline thickness of the SHM), SHM displacement (peak-to-peak amplitude of SHM movement), SHM difference (SHM displacement - SHM thickness), SHM ratio (SHM displacement/SHM thickness), peak-to-peak time, and total duration. A videofluoroscopic swallowing study (VFSS) was performed.

RESULTS: Significant differences were found in SHM displacement and SHM difference according to dysphagia severity (P<0.001). The SHM ratio, total duration (P<0.001), and peak-to-peak time (P=0.001) differed significantly according to the patients' underlying diseases. The pharyngeal delay time and penetration-aspiration scale from the VFSS demonstrated significant negative correlations with SHM displacement and difference (P<0.001). By combining SHM difference and total duration, patients with dysphagia could be distinguished from healthy controls, with the highest negative predictive value of 95.6%.

CONCLUSIONS: Dynamic M-mode US of the SHM provided added value in evaluating the severity of dysphagia and differentiating swallowing mechanics of dysphagia related to underlying neurological disorders.

Dynamic M-mode US of the SHM can serve as a supportive tool for rapid screening and repetitive follow-up of patients with dysphagia, which would contribute to dysphagia rehabilitation in patients with various neurological disorders.}, } @article {pmid38332489, year = {2024}, author = {Dandl, S and Bender, A and Hothorn, T}, title = {Heterogeneous treatment effect estimation for observational data using model-based forests.}, journal = {Statistical methods in medical research}, volume = {33}, number = {3}, pages = {392-413}, pmid = {38332489}, issn = {1477-0334}, mesh = {Humans ; *Treatment Effect Heterogeneity ; Riluzole ; *Amyotrophic Lateral Sclerosis ; Linear Models ; }, abstract = {The estimation of heterogeneous treatment effects has attracted considerable interest in many disciplines, most prominently in medicine and economics. Contemporary research has so far primarily focused on continuous and binary responses where heterogeneous treatment effects are traditionally estimated by a linear model, which allows the estimation of constant or heterogeneous effects even under certain model misspecifications. More complex models for survival, count, or ordinal outcomes require stricter assumptions to reliably estimate the treatment effect. Most importantly, the noncollapsibility issue necessitates the joint estimation of treatment and prognostic effects. Model-based forests allow simultaneous estimation of covariate-dependent treatment and prognostic effects, but only for randomized trials. In this paper, we propose modifications to model-based forests to address the confounding issue in observational data. In particular, we evaluate an orthogonalization strategy originally proposed by Robinson (1988, Econometrica) in the context of model-based forests targeting heterogeneous treatment effect estimation in generalized linear models and transformation models. We found that this strategy reduces confounding effects in a simulated study with various outcome distributions. We demonstrate the practical aspects of heterogeneous treatment effect estimation for survival and ordinal outcomes by an assessment of the potentially heterogeneous effect of Riluzole on the progress of Amyotrophic Lateral Sclerosis.}, } @article {pmid38331161, year = {2024}, author = {Golia, MT and Frigerio, R and Pucci, S and Sironi, F and Margotta, C and Pasetto, L and Testori, C and Berrone, E and Ingravalle, F and Chiari, M and Gori, A and Duchi, R and Perota, A and Bergamaschi, L and D'Angelo, A and Cagnotti, G and Galli, C and Corona, C and Bonetto, V and Bendotti, C and Cretich, M and Colombo, SF and Verderio, C}, title = {Changes in glial cell activation and extracellular vesicles production precede the onset of disease symptoms in transgenic hSOD1[G93A] pigs.}, journal = {Experimental neurology}, volume = {374}, number = {}, pages = {114716}, doi = {10.1016/j.expneurol.2024.114716}, pmid = {38331161}, issn = {1090-2430}, mesh = {Mice ; Animals ; Humans ; Swine ; Superoxide Dismutase-1/genetics ; Motor Neurons/metabolism ; Superoxide Dismutase/genetics ; Mice, Transgenic ; *Amyotrophic Lateral Sclerosis/pathology ; Spinal Cord/pathology ; Neuroglia/pathology ; *Extracellular Vesicles ; Biomarkers/metabolism ; Peptides/metabolism ; Disease Models, Animal ; }, abstract = {SOD1 gene is associated with progressive motor neuron degeneration in the familiar forms of amyotrophic lateral sclerosis. Although studies on mutant human SOD1 transgenic rodent models have provided important insights into disease pathogenesis, they have not led to the discovery of early biomarkers or effective therapies in human disease. The recent generation of a transgenic swine model expressing the human pathological hSOD1[G93A] gene, which recapitulates the course of human disease, represents an interesting tool for the identification of early disease mechanisms and diagnostic biomarkers. Here, we analyze the activation state of CNS cells in transgenic pigs during the disease course and investigate whether changes in neuronal and glial cell activation state can be reflected by the amount of extracellular vesicles they release in biological fluids. To assess the activation state of neural cells, we performed a biochemical characterization of neurons and glial cells in the spinal cords of hSOD1[G93A] pigs during the disease course. Quantification of EVs of CNS cell origin was performed in cerebrospinal fluid and plasma of transgenic pigs at different disease stages by Western blot and peptide microarray analyses. We report an early activation of oligodendrocytes in hSOD1[G93A] transgenic tissue followed by astrocyte and microglia activation, especially in animals with motor symptoms. At late asymptomatic stage, EV production from astrocytes and microglia is increased in the cerebrospinal fluid, but not in the plasma, of transgenic pigs reflecting donor cell activation in the spinal cord. Estimation of EV production by biochemical analyses is corroborated by direct quantification of neuron- and microglia-derived EVs in the cerebrospinal fluid by a Membrane Sensing Peptide enabled on-chip analysis that provides fast results and low sample consumption. Collectively, our data indicate that alteration in astrocytic EV production precedes the onset of disease symptoms in the hSOD[G93A] swine model, mirroring donor cell activation in the spinal cord, and suggest that EV measurements from the cells first activated in the ALS pig model, i.e. OPCs, may further improve early disease detection.}, } @article {pmid38330934, year = {2024}, author = {Yang, L and Li, Y and Zhang, S and Qian, H and Xu, W and Yu, J}, title = {Efficacy of Acupuncture Combined with Traditional Chinese Medicine Fumigation Therapy in Sequelae of Pelvic Inflammatory Disease: A Systematic Review and Meta-Analysis.}, journal = {Complementary medicine research}, volume = {31}, number = {2}, pages = {175-186}, doi = {10.1159/000536101}, pmid = {38330934}, issn = {2504-2106}, mesh = {Humans ; *Acupuncture Therapy/methods ; *Fumigation/methods ; *Medicine, Chinese Traditional/methods ; *Pelvic Inflammatory Disease/therapy ; Combined Modality Therapy ; Female ; }, abstract = {BACKGROUND AND OBJECTIVE: Acupuncture combined with traditional Chinese medicine fumigation is increasingly being used in treating sequelae of pelvic inflammatory disease (SPID). However, there is a lack of meta-analysis on the effectiveness of acupuncture combined with traditional Chinese medicine fumigation in treating SPID. The aim of this study was to assess the feasibility of combining acupuncture with traditional Chinese medicine fumigation in the treatment of SPID.

METHODS: We searched eight databases for studies on acupuncture combined with traditional Chinese medicine fumigation for the treatment of SPID from the date of establishment to October 29, 2022. We assessed the quality of included studies by using the Cochrane bias risk tool. Pooled results were expressed as risk ratios (RRs), with a 95% confidence interval (CI). In addition, we identified sources of heterogeneity by sensitivity analysis, assessed publication bias by Egger's test, and assessed the quality of the evidence by Grades of Recommendation, Assessment, Development, and Evaluation (GRADE). All statistical analyses were performed by Review Manager 5.3 and Stata 14.

RESULTS: Finally, seven studies with a total of 663 participants were included. We found a significant difference in the total effective rate in the acupuncture combined with the fumigation group compared with the acupuncture group in the treatment of SPID (RR = 1.17, 95% CI [1.09, 1.25], p = 0.0001 < 0.05; I2 = 0%; 6 trials), and a significant difference in the total effective rate in the acupuncture combined with fumigation group compared with the fumigation group in the treatment of SPID (RR = 1.42, 95% CI [1.21, 1.66], p = 0.0001 < 0.05; 5 trials).

CONCLUSION: The clinical efficacy of acupuncture combined with herbal fumigation in the treatment of SPID is relatively good. Larger scale studies are needed in the future.

UNLABELLED: Hintergrund und ZielAkupunktur in Kombination mit Fumigation, einem Verfahren der Traditionellen Chinesischen Medizin, wird zunehmend in der Behandlung von Folgeerscheinungen von Beckenentzündungen (SPID; sequelae of pelvic inflammatory disease) eingesetzt. Es mangelt jedoch an Metaanalysen zur Wirksamkeit der Akupunktur in Kombination mit Fumigation gemäß der Traditionellen Chinesischen Medizin in der Behandlung von SPID. Das Ziel dieser Studie ist die Beurteilung der Machbarkeit der Kombination aus Akupunktur und Fumigation gemäß der Traditionellen Chinesischen Medizin in der Behandlung von SPID.MethodenWir durchsuchten acht Datenbanken nach Studien zur Akupunktur in Kombination mit Fumigation gemäß der Traditionellen Chinesischen Medizin in der Behandlung von Folgeerscheinungen von SPID von der Einrichtung bis zum 29. Oktober 2022. Wir beurteilten die Qualität der eingeschlossenen Studien mit dem Cochrane-Tool zur Bewertung des Bias-Risikos. Die gepoolten Ergebnisse wurden als Risikoquotient (RR; risk ratio) mit 95%-Konfidenzintervall (KI) ausgedrückt. Zusätzlich identifizierten wir Quellen für Heterogenität mittels Sensitivitätsanalyse, beurteilten den Publikations-Bias mittels Egger-Test und bewerteten die Qualität der Evidenz nach Grad der Empfehlungsstärke, Beurteilung, Entwicklung und Evaluierung (GRADE). Alle statistischen Analysen erfolgten mit Review Manager 5.3 und Stata 14.ErgebnisseIm Endeffekt wurden 7 Studien mit insgesamt 663 Teilnehmern eingeschlossen. Wir fanden einen signifikanten Unterschied in der Gesamt-Effektivitätsrate bei der Gruppe, die zur Behandlung von SPID Akupunktur in Kombination mit Fumigation erhielt, im Vergleich zur reinen Akupunkturgruppe (RR = 1,17; 95%-KI [1,09; 1,25]; p = 0,0001 < 0,05; I2-Wert = 0%; 6 Studien), und einen signifikanten Unterschied in der Gesamt-Effektivitätsrate bei der Gruppe, die zur Behandlung von SPID Akupunktur in Kombination mit Fumigation erhielt, im Vergleich zur reinen Fumigationsgruppe (RR = 1,42; 95%-KI [1,21; 1,66]; p = 0,0001 < 0,05; 5 Studien).SchlussfolgerungDie klinische Wirksamkeit der Akupunktur in Kombination mit Kräuter-Fumigation zur Behandlung von SPID ist relativ gut. Zukünftig sind größere Studien erforderlich.}, } @article {pmid38330929, year = {2024}, author = {Fronczek, M and Kopacz, K and Kopacz, Ł and Padula, G}, title = {The Role of Objective Movement Analysis in the Control of Yoga Asanas: A Case Study.}, journal = {Complementary medicine research}, volume = {31}, number = {2}, pages = {201-209}, doi = {10.1159/000535312}, pmid = {38330929}, issn = {2504-2106}, mesh = {*Yoga ; Humans ; Female ; Adult ; Electromyography ; *Muscle, Skeletal/physiology ; *Postural Balance/physiology ; Movement/physiology ; Biomechanical Phenomena ; }, abstract = {INTRODUCTION: Yoga is classified as a form of complementary and alternative medicine. It can be used in many disciplines including physiotherapy, medicine, and sport. The objective of the study was to identify possible biomechanical problems during yoga practice and to minimize the risk of injury.

CASE PRESENTATION: Objective evaluation of the symmetry of asanas, balance, stability, and muscle tension was provided in case of a 37-year-old woman, practicing mainly aerial and Hatha yoga for 6 years. The bigger body tilt and deviations in center of pressure (COP) parameters were observed in tadasana during forward examinations. In tadasana, the highest muscle activity was observed in the rectus femoris. In case of forward tadasana observation, the highest activity was found in the gastrocnemius and in the lumbar portion of the erector spinae. During backward tadasana trial, the most active were the tibialis anterior and rectus femoris muscles. In garudasana and natarajasana, the symmetry of the trunk position in relation to the lower limbs was observed, regardless of the supporting limb. In the same way, COP parameters in garudasana were similar regardless of the supporting limb. However, in natarajasana, the higher COP displacement parameters were observed in the case of the nondominant supporting limb. As for the electromyographic evaluation of garudasana and natarajasana, the highest muscle activity was observed in the lumbar portion of the erector spinae. In chakrasana, a slightly greater angle of the hip extension was observed in the left hip. A higher muscle activity in chakrasana was observed in the lumbar portion of the right erector spinae. In sirsasana, no significant displacements of the cervical spine were observed, but a higher activity of the left sternocleidomastoid muscle was found.

CONCLUSION: With the use of objective movement analysis, possible biomechanical problems were identified. Attention should be paid to the normalization of the tension in the lumbar part of the right erector spinae and the right sternocleidomastoid muscle, as well as to the balance training in positions on the nondominant lower limb. Objective movement analysis can be a useful tool for instructors or physiotherapists to adjust yoga programs and correct asanas in order to avoid future injuries.

UNLABELLED: EinleitungYoga gilt als Form der Komplementär- und Alternativmedizin. Es ist in vielen Disziplinen einsetzbar, von Physiotherapie über Medizin bis Sport. Das Ziel dieser Studie war es, mögliche biomechanische Probleme bei der Ausübung von Yoga zu identifizieren, um das Verletzungsrisiko zu minimieren.Vorstellung des FallsEine objektive Beurteilung der Symmetrie der Asanas, des Gleichgewichts, der Stabilität und der Muskelspannung erfolgte bei einer 37-jährigen Frau, die seit 6 Jahren hauptsächlich Aerial- und Hatha-Yoga praktiziert. Stärkere Körperneigung und Abweichungen bei Druckmittelpunkt-Parametern wurden in Tadasana bei der Vorwärts-Beobachtung festgestellt. In Tadasana wurde die höchste Muskelaktivität im Rectus femoris beobachtet. Bei der Tadasana-Vorwärts-Beobachtung war die höchste Aktivität im Gastrocnemius und im lumbalen Anteil des Erector spinae zu verzeichnen. Während der Tadasana-Rückwärts-Übung waren die aktivsten Muskeln der Tibialis anterior und Rectus femoris. In Garudasana und Natarajasana wurde die Symmetrie der Rumpfposition im Verhältnis zu den unteren Gliedmaßen unabhängig von der belasteten Gliedmaße beobachtet. Ebenso waren die Parameter des Druckmittelpunkts (DMP) in Garudasana unabhängig von der belasteten Gliedmaße vergleichbar. In Natarajasana wurden jedoch höhere Parameter der DMP-Verschiebung bei der nicht-dominanten belasteten Gliedmaße beobachtet. Bei der elektromyografischen Auswertung von Garudasana und Natarajasana wurde die höchste Muskelaktivität im lumbalen Anteil des Erector spinae beobachtet. In Chakrasana wurde ein etwas größerer Winkel der Hüftstreckung im linken Hüftgelenk beobachtet. Eine höhere Muskelaktivität in Chakrasana wurde im lumbalen Anteil des rechten Erector spinae beobachtet. In Sirsasana wurden keine signifikanten Verschiebungen der Halswirbelsäule beobachtet, jedoch war eine höhere Aktivität des linken Sternocleidomastoideus zu verzeichnen.SchlussfolgerungMit Hilfe einer objektiven Bewegungsanalyse wurden mögliche biomechanische Probleme identifiziert. Mit besonderer Aufmerksamkeit sollte auf die Normalisierung der Spannung im lumbalen Anteil des rechten Erector spinae und des rechten Sternocleidomastoideus sowie auf die Schulung des Gleichgewichts in Positionen auf der nicht-dominanten unteren Extremität geachtet werden. Die objektive Bewegungsanalyse kann ein nützliches Instrument für Instruktoren oder Physiotherapeuten sein, um Yoga-Programme anzupassen und Asanas zu korrigieren, um Verletzungen vorzubeugen.}, } @article {pmid38330924, year = {2024}, author = {Leedasawat, P and Sangvatanakul, P and Tungsukruthai, P and Kamalashiran, C and Phetkate, P and Patarajierapun, P and Sriyakul, K}, title = {The Efficacy and Safety of Chinese Eye Exercise of Acupoints in Dry Eye Patients: A Randomized Controlled Trial.}, journal = {Complementary medicine research}, volume = {31}, number = {2}, pages = {149-159}, doi = {10.1159/000536516}, pmid = {38330924}, issn = {2504-2106}, mesh = {Adult ; Female ; Humans ; Male ; Middle Aged ; Young Adult ; *Acupuncture Points ; *Acupuncture Therapy/methods ; *Dry Eye Syndromes/therapy ; Single-Blind Method ; Thailand ; Treatment Outcome ; }, abstract = {INTRODUCTION: Dry eye disorder (DED) is a growing global issue linked to excessive digital screen time. Chinese eye exercise of acupoint (CEA), a set of self-massages on shared Chinese acupuncture (CA), has been used to reduce visual-related ocular symptoms and possibly as an alternative treatment for DED. This study aimed to assess the efficacy and safety of CEA.

METHODS: A single-blind randomized controlled trial was conducted at Thammasat University Hospital in Thailand, recruiting 56 participants aged 20-60 years, equally divided into two groups: the treatment group with CEA and the control group with standard lid hygiene treatment (STD). The intervention program lasted 12 weeks.

MAIN OUTCOME MEASURES: Ocular Surface Disease Index (OSDI), tear break-up time (TBUT), Schirmer-I test (SIT), corneal surface staining (CSS), and self-recorded forms for safety and adverse effects were measured at baseline, week 4, and week 12. An independent sample t test, paired t test, and repeated measures (ANOVA) were used to compare results between both groups, study visits, and primary and secondary outcome measurements, respectively. The p values <0.05 were considered statistically significant.

RESULTS: The characteristics were not statistically different between both groups at the baseline. The mean OSDI scores were significantly reduced in both groups at week 4 and week 12 compared to baseline (p value <0.05). Additionally, both CEA and STD showed significant improvement in TBUT and SIT (p value <0.05). CSS was significantly improved only in the CEA groups (p value <0.05). No significant differences were observed between the study groups, except for SIT at week 12 (p value <0.05). For the safety, there were no adverse side effects in either group.

CONCLUSION: CEA seemed to be as effective as STD in improving the OSDI, TBUT, and SIT of DED without causing any side effects.

UNLABELLED: EinleitungDas Trockene Auge (Dry eye disorder, DED) ist weltweit ein zunehmendes Problem, das mit übermässiger Bildschirmarbeit zusammenhängt. Die chinesische Augenübung der Akupunkturpunkte (Chinese eye exercise of acupoint, CEA), eine Reihe von Selbstmassagen an gemeinsamen CA-Akupunkturpunkten, wird zur Linderung visusbezogener Augensymptome und als mögliche alternative Behandlung für DED eingesetzt. Mit dieser Studie sollte die Wirksamkeit und Sicherheit von CEA bewertet werden.MethodenAm Thammasat-Universitätsklinikum in Thailand wurde eine einfach verblindete, randomisierte, kontrollierte Studie mit 56 Teilnehmern im Alter von 20 bis 60 Jahren durchgeführt, die zu gleichen Teilen zwei Gruppen zugewiesen wurden: die Behandlungsgruppe mit CEA und die Kontrollgruppe, die die Standard-Lidhygienebehandlung erhielt (STD). Das Interventionsprogramm dauerte 12 Wochen. Die Haupt-Zielkriterien, der Ocular Surface Disease Index (OSDI), die Tränenfilmaufreisszeit (tear break-up time, TBUT), der Schirmer-I-Test (SIT), das Corneal Surface Staining (CSS) und Selbstauskunftsformulare zur Sicherheit und zu unerwünschten Wirkungen wurden zu Beginn der Behandlung, in Woche 4 und in Woche 12 ermittelt. Für den Vergleich der Ergebnisse zwischen den beiden Gruppen, den Studienvisiten bzw. den primären und sekundären Zielkriterien wurden ein t Test für unabhängige Stichproben, ein t Test für paarige Stichproben und eine ANOVA mit Messwiederholungen verwendet. p-Werte <0,05 galten als statistisch signifikant.ErgebnisseHinsichtlich der Merkmale bestand zwischen den beiden Gruppen kein statistischer Unterschied bei Studienbeginn. In beiden Gruppen fielen die mittleren OSDI-Scores in Woche 4 und Woche 12 im Vergleich zum Ausgangswert signifikant geringer aus (p-Wert <0,05). Darüber hinaus zeigten sowohl die CEA- als auch die STD-Gruppe eine signifikante Verbesserung der TBUT- und SIT-Werte (p-Wert <0,05). Das CSS verbesserte sich nur in der CEA-Gruppe signifikant (p-Wert <0,05). Zwischen den Studiengruppen waren keine signifikanten Unterschiede zu beobachten, ausser beim SIT in Woche 12 (p-Wert <0,05). Was die Sicherheit betrifft, so traten in beiden Gruppen keine unerwünschten Nebenwirkungen auf.SchlussfolgerungDie CEA schien die OSDI-, TBUT- und SIT-Werte bei DED ebenso wirksam zu verbessern wie die Standardbehandlung, ohne Nebenwirkungen zu verursachen.}, } @article {pmid38330475, year = {2024}, author = {Stavros, K}, title = {Genetic Myelopathies.}, journal = {Continuum (Minneapolis, Minn.)}, volume = {30}, number = {1}, pages = {119-132}, pmid = {38330475}, issn = {1538-6899}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis ; *Muscular Atrophy, Spinal/diagnosis ; *Spastic Paraplegia, Hereditary/diagnosis ; *Spinal Cord Diseases/diagnosis/genetics/therapy ; }, abstract = {OBJECTIVE: This article provides an overview of genetic myelopathies, a diverse group of inherited, degenerative conditions that may be broadly categorized as motor neuron disorders, disorders of spinocerebellar degeneration, leukodystrophies, and hereditary spastic paraplegia. Clinical examples from each category are provided to illustrate the spectrum of genetic myelopathies and their distinguishing features that aid in differentiating genetic myelopathies from potentially treatable acquired causes of myelopathy.

LATEST DEVELOPMENTS: Advances in genetic testing have vastly enhanced current knowledge of genetic myelopathies and the ability to diagnose and provide appropriate counseling to patients and their families. However, potential health care disparities in access to genetic testing is a topic that must be further explored. Although treatment for most of these conditions is typically supportive, there have been recent therapeutic breakthroughs in treatments for amyotrophic lateral sclerosis, spinal muscular atrophy, and Friedreich ataxia.

ESSENTIAL POINTS: Genetic myelopathies may present with chronic and progressive symptoms, a family history of similar symptoms, and involvement of other structures outside of the spinal cord. Imaging often shows spinal cord atrophy, but cord signal change is rare. Exclusion of reversible causes of myelopathy is a key step in the diagnosis. There are many different causes of genetic myelopathies, and in some cases, symptoms may overlap, which underscores the utility of genetic testing in confirming the precise underlying neurologic condition.}, } @article {pmid38329887, year = {2024}, author = {Sanghai, N and Vuong, B and Burak Berk, A and Afridi, MSK and Tranmer, GK}, title = {Current Small Molecule-Based Medicinal Chemistry Approaches for Neurodegeneration Therapeutics.}, journal = {ChemMedChem}, volume = {19}, number = {9}, pages = {e202300705}, doi = {10.1002/cmdc.202300705}, pmid = {38329887}, issn = {1860-7187}, support = {//Department of Human Anatomy and Cell Science, University of Manitoba/ ; //College of Pharmacy, Department of Pharmacology & Therapeutics, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba/ ; }, mesh = {Humans ; *Neurodegenerative Diseases/drug therapy/metabolism ; *Small Molecule Libraries/chemistry/pharmacology/chemical synthesis ; *Neuroprotective Agents/chemistry/pharmacology/chemical synthesis ; Blood-Brain Barrier/metabolism/drug effects ; Chemistry, Pharmaceutical ; Molecular Structure ; }, abstract = {Neurodegenerative diseases (NDDs) like Alzheimer's disease (AD), Parkinson's disease (PD), and Amyotrophic lateral sclerosis (ALS) possess multifactorial aetiologies. In recent years, our understanding of the biochemical and molecular pathways across NDDs has increased, however, new advances in small molecule-based therapeutic strategies targeting NDDs are obscure and scarce. Moreover, NDDs have been studied for more than five decades, however, there is a paucity of drugs that can treat NDDs. Further, the highly lipoidal blood-brain barrier (BBB) limits the uptake of many therapeutic molecules into the brain and is a complicating factor in the development of new agents to treat neurodegeneration. Considering the highly complex nature of NDDs, the association of multiple risk factors, and the challenges to overcome the BBB junction, medicinal chemists have developed small organic molecule-based novel approaches to target NDDs over the last few decades, such as designing lipophilic molecules and applying prodrug strategies. Attempts have been made to utilize a multitarget approach to modulate different biochemical molecular pathways involved in NDDs, in addition to, medicinal chemists making better decisions in identifying optimized drug candidates for the central nervous system (CNS) by using web-based computational tools. To increase the clinical success of these drug candidates, an in vitro assay modeling the BBB has been utilized by medicinal chemists in the pre-clinical phase as a further screening measure of small organic molecules. Herein, we examine some of the intriguing strategies taken by medicinal chemists to design small organic molecules to combat NDDs, with the intention of increasing our awareness of neurodegenerative therapeutics.}, } @article {pmid38328178, year = {2024}, author = {Arnold, FJ and Cui, Y and Michels, S and Colwin, MR and Stockford, C and Ye, W and Tam, OH and Menon, S and Situ, WG and Ehsani, KCK and Howard, S and Hammell, MG and Li, W and La Spada, AR}, title = {TDP-43 dysregulation of polyadenylation site selection is a defining feature of RNA misprocessing in ALS/FTD and related disorders.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2024.01.22.576709}, pmid = {38328178}, issn = {2692-8205}, support = {RF1 NS118570/NS/NINDS NIH HHS/United States ; }, abstract = {Nuclear clearance and cytoplasmic aggregation of the RNA-binding protein TDP-43 are observed in many neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS) and fronto- temporal dementia (FTD). Although TDP-43 dysregulation of splicing has emerged as a key event in these diseases, TDP-43 can also regulate polyadenylation; yet, this has not been adequately studied. Here, we applied the dynamic analysis of polyadenylation from RNA-seq (DaPars) tool to ALS/FTD transcriptome datasets, and report extensive alternative polyadenylation (APA) upon TDP-43 alteration in ALS/FTD cell models and postmortem ALS/FTD neuronal nuclei. Importantly, many identified APA genes highlight pathways implicated in ALS/FTD pathogenesis. To determine the functional significance of APA elicited by TDP-43 nuclear depletion, we examined microtubule affinity regulating kinase 3 (MARK3). Nuclear loss of TDP-43 yielded increased expression of MARK3 transcripts with longer 3'UTRs, resulting in greater transcript stability and elevated MARK3 protein levels, which promotes increased neuronal tau S262 phosphorylation. Our findings define changes in polyadenylation site selection as a previously unrecognized feature of TDP-43-driven disease pathology in ALS/FTD and highlight a potentially novel mechanistic link between TDP-43 dysfunction and tau regulation.}, } @article {pmid38328059, year = {2024}, author = {Zeng, Y and Lovchykova, A and Akiyama, T and Liu, C and Guo, C and Jawahar, VM and Sianto, O and Calliari, A and Prudencio, M and Dickson, DW and Petrucelli, L and Gitler, AD}, title = {TDP-43 nuclear loss in FTD/ALS causes widespread alternative polyadenylation changes.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {38328059}, issn = {2692-8205}, support = {R35 NS097273/NS/NINDS NIH HHS/United States ; R01 NS120992/NS/NINDS NIH HHS/United States ; P01 NS084974/NS/NINDS NIH HHS/United States ; RF1 AG064690/AG/NIA NIH HHS/United States ; U54 NS123743/NS/NINDS NIH HHS/United States ; T32 AG047126/AG/NIA NIH HHS/United States ; RF1 NS120992/NS/NINDS NIH HHS/United States ; R01 AG064690/AG/NIA NIH HHS/United States ; R35 NS097263/NS/NINDS NIH HHS/United States ; }, abstract = {In frontotemporal dementia and amyotrophic lateral sclerosis, the RNA-binding protein TDP-43 is depleted from the nucleus. TDP-43 loss leads to cryptic exon inclusion but a role in other RNA processing events remains unresolved. Here, we show that loss of TDP-43 causes widespread changes in alternative polyadenylation, impacting expression of disease-relevant genes (e.g., ELP1, NEFL, and TMEM106B) and providing evidence that alternative polyadenylation is a new facet of TDP-43 pathology.}, } @article {pmid38328053, year = {2024}, author = {Yan, X and Kuster, D and Mohanty, P and Nijssen, J and Pombo-García, K and Rizuan, A and Franzmann, TM and Sergeeva, A and Passos, PM and George, L and Wang, SH and Shenoy, J and Danielson, HL and Honigmann, A and Ayala, YM and Fawzi, NL and Mittal, J and Alberti, S and Hyman, AA}, title = {Intra-condensate demixing of TDP-43 inside stress granules generates pathological aggregates.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {38328053}, issn = {2692-8205}, support = {R01 NS114289/NS/NINDS NIH HHS/United States ; }, abstract = {Cytosolic aggregation of the nuclear protein TDP-43 is associated with many neurodegenerative diseases, but the triggers for TDP-43 aggregation are still debated. Here, we demonstrate that TDP-43 aggregation requires a double event. One is up-concentration in stress granules beyond a threshold, and the other is oxidative stress. These two events collectively induce intra-condensate demixing, giving rise to a dynamic TDP-43 enriched phase within stress granules, which subsequently transitions into pathological aggregates. Mechanistically, intra-condensate demixing is triggered by local unfolding of the RRM1 domain for intermolecular disulfide bond formation and by increased hydrophobic patch interactions in the C-terminal domain. By engineering TDP-43 variants resistant to intra-condensate demixing, we successfully eliminate pathological TDP-43 aggregates in cells. We conclude that up-concentration inside condensates and simultaneous exposure to environmental stress could be a general pathway for protein aggregation, with intra-condensate demixing constituting a key intermediate step.}, } @article {pmid38325718, year = {2024}, author = {Cuevas, EP and Martinez-Gonzalez, L and Gordillo, C and Tosat-Bitrián, C and Pérez de la Lastra, C and Sáenz, A and Gil, C and Palomo, V and Martin-Requero, Á and Martinez, A}, title = {Casein kinase 1 inhibitor avoids TDP-43 pathology propagation in a patient-derived cellular model of amyotrophic lateral sclerosis.}, journal = {Neurobiology of disease}, volume = {192}, number = {}, pages = {106430}, doi = {10.1016/j.nbd.2024.106430}, pmid = {38325718}, issn = {1095-953X}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism ; Casein Kinase I ; *Neurodegenerative Diseases ; *Neuroblastoma ; DNA-Binding Proteins/metabolism ; }, abstract = {Amyotrophic lateral sclerosis is a fatal neurodegenerative disease without a cure to reverse its progression. Its main hallmark is the nuclear protein TDP-43, which undergoes different post-translational modifications leading to a loss of function in the nucleus and an increase in toxicity in the cytoplasm. Previous reports have indicated that pathogenic TDP-43 exhibits prion-like propagation in various contexts. With the aim of advancing therapeutics focused on preventing the propagation of TDP-43 pathology, we studied the potential role of pathogenic TDP-43 in lymphoblasts from sporadic ALS patients. We used lymphoblastoid cell lines from sporadic ALS patients as a source of pathogenic forms of TDP-43, and healthy human cells (lymphoblasts, myoblasts, neuroblastoma SH-SY5Y, or osteosarcoma U2OS) as recipient cells to investigate the seeding and spread of TDP-43 proteinopathy. Furthermore, we evaluated the potential of targeting TDP-43 phosphorylation with a CK-1 inhibitor to prevent the propagation of the pathology. The results presented herein indicate that pathogenic forms of TDP-43 are secreted into the extracellular medium of sporadic ALS lymphoblasts and could be transported by extracellular vesicles, spreading TDP-43 pathology to healthy cells. Moreover, tunneling nanotubes have also been discovered in pathological cells and may be involved in the transport of TDP-43. Interestingly, targeting TDP-43 phosphorylation with an in-house designed CK-1 inhibitor (IGS2.7) was sufficient to halt TDP-43 pathology transmission, in addition to its known effects on restoring the homeostasis of TDP-43 protein in patients-derived cells.}, } @article {pmid38325473, year = {2024}, author = {Xu, Y and Nie, J and Lu, C and Hu, C and Chen, Y and Ma, Y and Huang, Y and Lu, L}, title = {Effects and mechanisms of bisphenols exposure on neurodegenerative diseases risk: A systemic review.}, journal = {The Science of the total environment}, volume = {919}, number = {}, pages = {170670}, doi = {10.1016/j.scitotenv.2024.170670}, pmid = {38325473}, issn = {1879-1026}, mesh = {Animals ; Humans ; *Neurodegenerative Diseases/chemically induced ; *Alzheimer Disease ; *Parkinson Disease/etiology/metabolism ; Brain/metabolism ; Oxidative Stress/physiology ; }, abstract = {Environmental bisphenols (BPs) pose a global threat to human health because of their extensive use as additives in plastic products. BP residues are increasing in various environmental media (i.e., water, soil, and indoor dust) and biological and human samples (i.e., serum and brain). Both epidemiological and animal studies have determined an association between exposure to BPs and an increased risk of neurodegenerative diseases (e.g., Parkinson's disease, Alzheimer's disease, and amyotrophic lateral sclerosis), including cognitive abnormalities and behavioral disturbances. Hence, understanding the biological responses to different BPs is essential for prevention, and treatment. This study provides an overview of the underlying pathogenic molecular mechanisms as a valuable basis for understanding neurodegenerative disease responses to BPs, including accumulation of misfolded proteins, reduction of tyrosine hydroxylase and dopamine, abnormal hormone signaling, neuronal death, oxidative stress, calcium homeostasis, and inflammation. These findings provide new insights into the neurotoxic potential of BPs and ultimately contribute to a comprehensive health risk evaluation.}, } @article {pmid38325382, year = {2024}, author = {Yan, J and Wang, YM and Hellwig, A and Bading, H}, title = {TwinF interface inhibitor FP802 stops loss of motor neurons and mitigates disease progression in a mouse model of ALS.}, journal = {Cell reports. Medicine}, volume = {5}, number = {2}, pages = {101413}, pmid = {38325382}, issn = {2666-3791}, mesh = {Mice ; Animals ; Humans ; *Amyotrophic Lateral Sclerosis/drug therapy/pathology ; Superoxide Dismutase/metabolism/pharmacology/therapeutic use ; Mice, Transgenic ; Motor Neurons/metabolism/pathology ; Disease Models, Animal ; Disease Progression ; *TRPM Cation Channels ; }, abstract = {Toxic signaling by extrasynaptic NMDA receptors (eNMDARs) is considered an important promoter of amyotrophic lateral sclerosis (ALS) disease progression. To exploit this therapeutically, we take advantage of TwinF interface (TI) inhibition, a pharmacological principle that, contrary to classical NMDAR pharmacology, allows selective elimination of eNMDAR-mediated toxicity via disruption of the NMDAR/TRPM4 death signaling complex while sparing the vital physiological functions of synaptic NMDARs. Post-disease onset treatment of the SOD1[G93A] ALS mouse model with FP802, a modified TI inhibitor with a safe pharmacology profile, stops the progressive loss of motor neurons in the spinal cord, resulting in a reduction in the serum biomarker neurofilament light chain, improved motor performance, and an extension of life expectancy. FP802 also effectively blocks NMDA-induced death of neurons in ALS patient-derived forebrain organoids. These results establish eNMDAR toxicity as a key player in ALS pathogenesis. TI inhibitors may provide an effective treatment option for ALS patients.}, } @article {pmid38324182, year = {2024}, author = {Jiang, Z and Gu, XJ and Su, WM and Duan, QQ and Yin, KF and Ren, YL and Wang, Y and Cao, B and Chen, YP}, title = {Discovery and Exploration of Lipid-Modifying Drug Targets for ALS by Mendelian Randomization.}, journal = {Molecular neurobiology}, volume = {61}, number = {9}, pages = {6572-6583}, pmid = {38324182}, issn = {1559-1182}, support = {2022YFC2703101//the National Key Research and Development Program of China/ ; 2022NSFSC0749//the National Natural Science Fund of Sichuan/ ; 2021YFS0051//the Science and Technology Bureau Fund of Sichuan Province/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/drug therapy ; *Mendelian Randomization Analysis ; Phenotype ; Drug Discovery ; Polymorphism, Single Nucleotide/genetics ; Lipids/blood ; Molecular Targeted Therapy ; Genetic Predisposition to Disease ; }, abstract = {Observational studies have faced challenges in identifying replicable causes for amyotrophic lateral sclerosis (ALS). To address this, we employed an unbiased and data-driven approach to discover and explore potential causal exposures using two-sample Mendelian randomization (MR) analyses. In the phenotype discovery stage, we assessed 3948 environmental exposures from the UK Biobank and utilized ALS summary statistics (Europeans, 20,806 cases, 59,804 controls) as the outcome within a phenome-wide MR pipeline. Through a range of sensitivity analyses, two medication traits were identified to be protective for ALS. In the target exploration stage, we further conducted drug target MR analyses using the latest and trans-ethnic summary data on lipid-related traits and ALS (Europeans, 27,205 cases, 110,881 controls; East Asians, 1234 cases, 2850 controls). Our aim was to explore potential causal drug targets through six lipid-modifying effects. These comprehensive analyses revealed significant findings. Specifically, "cholesterol-lowering medication" and "atorvastatin" survived predefined criteria in the phenotype discovery stage and exhibited a protective effect on ALS. Further in the target exploration stage, we demonstrated that the therapeutic effect of APOB through LDL-lowering was associated with reduced ALS liability in Europeans (OR = 0.835, P = 5.61E - 5). Additionally, the therapeutic effect of APOA1 and LDLR through TC-lowering was associated with reduced ALS liability in East Asians (APOA1, OR = 0.859, P = 5.38E - 4; LDLR, OR = 0.910, P = 2.73E - 5). Overall, we propose potential protective effects of cholesterol-lowering drugs or statins on ALS risk from thousands of exposures. Our research also suggests APOB, APOA1, and LDLR as novel therapeutic targets for ALS and supports their potential protective mechanisms may be mediated by LDL-lowering or TC-lowering effects.}, } @article {pmid38324041, year = {2024}, author = {Harris, CM and Higgins, C and Mehta, AK}, title = {Trends in Specialty Palliative Care Service Utilization and In-Hospital Outcomes for Patients With Amyotrophic Lateral Sclerosis.}, journal = {Journal of palliative medicine}, volume = {27}, number = {4}, pages = {521-525}, doi = {10.1089/jpm.2023.0444}, pmid = {38324041}, issn = {1557-7740}, mesh = {Humans ; United States ; *Palliative Care ; *Amyotrophic Lateral Sclerosis/therapy ; Hospitals ; Hospitalization ; Patients ; }, abstract = {Background: Hospitalized people with amyotrophic lateral sclerosis (ALS) may benefit from specialty palliative care services (sPCS). Objective: To describe access to in-hospital sPCS for people with ALS (pALS). Methods: We compared years 2010-2011 to 2018-2019, and conducted trend analyses of sPCS from 2010 to 2019 stratified by race. Results: Of 103,193 pALS admitted during the study period, 13,885 (13.4%) received sPCS. Rates of sPCS increased over time (2010-2011: 8.9% vs. 2018-2019: 16.6%; p < 0.01). From 2010 to 2019, there was an increase in sPCS (p-trend<0.01) for all studied racial groups. Conclusions: Access to palliative care has increased over time for pALS admitted to hospitals in the United States.}, } @article {pmid38323662, year = {2024}, author = {Garcés, P and Amaro, A and Montecino, M and van Zundert, B}, title = {Inorganic polyphosphate: from basic research to diagnostic and therapeutic opportunities in ALS/FTD.}, journal = {Biochemical Society transactions}, volume = {52}, number = {1}, pages = {123-135}, doi = {10.1042/BST20230257}, pmid = {38323662}, issn = {1470-8752}, mesh = {Animals ; Mice ; Humans ; *Frontotemporal Dementia/metabolism/therapy ; *Amyotrophic Lateral Sclerosis/diagnosis/drug therapy/metabolism ; Polyphosphates ; *Alzheimer Disease ; *Parkinson Disease ; Mammals ; }, abstract = {Inorganic polyphosphate (polyP) is a simple, negatively charged biopolymer with chain lengths ranging from just a few to over a thousand ortho-phosphate (Pi) residues. polyP is detected in every cell type across all organisms in nature thus far analyzed. Despite its structural simplicity, polyP has been shown to play important roles in a remarkably broad spectrum of biological processes, including blood coagulation, bone mineralization and inflammation. Furthermore, polyP has been implicated in brain function and the neurodegenerative diseases amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), Alzheimer's disease and Parkinson's disease. In this review, we first address the challenges associated with identifying mammalian polyP metabolizing enzymes, such as Nudt3, and quantifying polyP levels in brain tissue, cultured neural cells and cerebrospinal fluid. Subsequently, we focus on recent studies that unveil how the excessive release of polyP by human and mouse ALS/FTD astrocytes contributes to these devastating diseases by inducing hyperexcitability, leading to motoneuron death. Potential implications of elevated polyP levels in ALS/FTD patients for innovative diagnostic and therapeutic approaches are explored. It is emphasized, however, that caution is required in targeting polyP in the brain due to its diverse physiological functions, serving as an energy source, a chelator for divalent cations and a scaffold for amyloidogenic proteins. Reducing polyP levels, especially in neurons, might thus have adverse effects in brain functioning. Finally, we discuss how activated mast cells and platelets also can significantly contribute to ALS progression, as they can massively release polyP.}, } @article {pmid38323575, year = {2024}, author = {Hamatani, T and Atsuta, N and Sano, F and Nakamura, R and Hayashi, Y and Sobue, G}, title = {ALSFRS-R decline rate prior to baseline is not useful for stratifying subsequent progression of functional decline.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {25}, number = {3-4}, pages = {388-399}, doi = {10.1080/21678421.2024.2309989}, pmid = {38323575}, issn = {2167-9223}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis ; Disease Progression ; Prognosis ; Registries ; Databases, Factual ; }, abstract = {OBJECTIVE: One of the difficulties in developing a novel drug for patients with amyotrophic lateral sclerosis (ALS) is the significant variation in the clinical course. To control this variation, a 12-week run-in period is used in some clinical trials. Based on the Amyotrophic Lateral Sclerosis Functional Rating Scale Revised (ALSFRS-R) change during the run-in period, only moderate progressors are selected in some clinical trials. Some reports showed that the ALSFRS-R progression rate was associated with survival. However, it is unclear whether the ALSFRS-R change in the run-in period is a useful prognostic factor of the ALSFRS-R change from baseline. In addition, we explore the inclusion criteria that could control the variability in ALS-function progression without setting a run-in period.

METHODS: We utilized the Japanese and US ALS registry databases (JaCALS and PRO-ACT). Patients were classified into three populations (rapid, moderate, and slow progressors) based on the ALSFRS-R change prior to baseline. We also classified patients into three prognostic populations based on the ALSFRS-R change from baseline. We confirmed whether each of the three populations were matched with their respective three prognostic populations.

RESULTS: Our data showed that the three groups classified by the ALSFRS-R change during the 12 weeks prior to baseline or by the rate of progression from onset to baseline did not accord with the three prognostic groups.

CONCLUSIONS: Our results showed that the ALSFRS-R change in the run-in period or from onset to baseline is not useful for stratifying subsequent progression of functional decline in clinical trials.}, } @article {pmid38323488, year = {2024}, author = {Downing, NR and Scafide, KN and Ali, Z and Hayat, MJ}, title = {Visibility of inflicted bruises by alternate light: Results of a randomized controlled trial.}, journal = {Journal of forensic sciences}, volume = {69}, number = {3}, pages = {880-887}, doi = {10.1111/1556-4029.15481}, pmid = {38323488}, issn = {1556-4029}, support = {2016-DN-BX-0147//National Institute of Justice, Office of Justice Programs, U.S. Department of Justice/ ; }, mesh = {Humans ; *Contusions/pathology ; Male ; Female ; Adult ; *Cross-Over Studies ; *Skin Pigmentation ; *Light ; Young Adult ; Middle Aged ; }, abstract = {Difficulty visualizing bruises resulting from interpersonal violence, especially in individuals with dark skin, contributes to disparities in access to justice. The purpose of this analysis was to compare bruise visibility of detected injuries using white light versus alternate light sources (ALS). Visibility was assessed using the 5-point Bruise Visibility Scale (BVS) for white light and the ALS Visibility Scale (AVS) for ALS. Bruises were induced using controlled application of a paintball to the upper arm on 157 healthy adults across six skin color categories. Using a crossover design, the light source used first to assess the bruise (white light or ALS) was randomized. Each bruise was examined up to 21 times over 4 weeks using white light and 10 combinations of wavelengths (350 nanometer [nm] - 535 nm) and colored filters (yellow, orange, and red). Multilevel modeling was used to analyze the repeated measures data with a total 20,103 bruise assessments. Results revealed 415 nm with yellow filter resulted in an almost 0.5-point increase in BVS/AVS score across all skin colors (Estimate = 0.46; 95% CI: 0.43, 0.49; p < 0.001), a clinically significant improvement in ability to visualize bruises. Conversely, 515 nm (Estimate = -0.80; 95% CI: -0.84, -0.76; p < 0.001) and 535 nm (Estimate = -0.64, 95% CI: -0.67, -0.60; p < 0.001) with red filter resulted in more than 0.5-point decrease in BVS/AVS score. The use of ALS is supported by the data and results in improved bruise visibility during medical forensic examinations.}, } @article {pmid38322130, year = {2023}, author = {Polverino, F and Sampaolo, S and Capuozzo, A and Fasolino, M and Aliberti, M and Satta, E and Santoriello, C and Polverino, M}, title = {Diagnosis of amyotrophic lateral sclerosis by respiratory function test.}, journal = {Multidisciplinary respiratory medicine}, volume = {18}, number = {1}, pages = {941}, pmid = {38322130}, issn = {1828-695X}, abstract = {The diagnostic criterion for amyotrophic lateral sclerosis (ALS) based on the findings of concomitant clinical and electrophysiological evidence of upper and lower motor neuron involvement may remain unsatisfied for months and in some patients, even for years in the early stage of the disease. Since respiratory involvement is an onset symptom of ALS in only 1-3% of patients, pulmonary assessment has never been considered useful in the early diagnosis of ALS. However, studies on pulmonary function are lacking, especially in those early stages where neurologic tests are also inconclusive. In contrast to the scarcity of data in the early stages, as the disease progresses, it is increasingly enriched by a rich set of symptoms and positive respiratory tests until respiratory failure occurs, which represents the main cause of death in ALS. Hereby we analyze the main pulmonary function tests (PFT) in the various stages of the disease, up to the recent evidence for the possibility of an early diagnosis.}, } @article {pmid38321352, year = {2024}, author = {Sathyamurthy, VH and Nagarajan, Y and Parvathi, VD}, title = {Mitochondria-Endoplasmic Reticulum Contact Sites (MERCS): A New Axis in Neuronal Degeneration and Regeneration.}, journal = {Molecular neurobiology}, volume = {61}, number = {9}, pages = {6528-6538}, pmid = {38321352}, issn = {1559-1182}, mesh = {Humans ; Animals ; *Mitochondria/metabolism ; *Endoplasmic Reticulum/metabolism ; Nerve Degeneration/pathology ; Nerve Regeneration/physiology ; Neurons/metabolism/pathology ; Neurodegenerative Diseases/metabolism/pathology ; Mitochondria Associated Membranes ; }, abstract = {Mitochondria-Endoplasmic Reticulum Contact Sites (MERCS) are dynamic structures whose physiological interaction is vital to direct life and death of the cell. A bevy of tethering proteins, mitofusin-1/2 (Mfn-1/2), glucose-regulated protein-75 (Grp-75), voltage-dependent anion channel-1 (VDAC1), and dynamic-related protein-1 (Drp1), plays an integral role in establishing and regulating this intricate intracellular communication. Dysregulation of this interplay leads to various neurodegenerative disorders, like Alzheimer's disease (AD), Parkinson's disease (PD), stroke, traumatic brain injury (TBI), amyotrophic lateral sclerosis (ALS), and frontotemporal dementia (FTD). Although there is an absence of a well-defined molecular background that dictates the pathway of MERCS, adequate exploration has resulted in preliminary data that suggests its cardinal role in neuroregeneration. The juxtaposition of mitochondria and ER has a critical function in cell senescence, thus regulating regeneration. Axonal regeneration and brain tissue regeneration, using reactive astrocytes, are studied most extensively. Overexpression of Grp-75 promoted axonal regeneration post a nerve injury. Attempts have been made to exploit MERCS as potential therapeutic drug targets for enhancing neuroregeneration and impeding neurodegeneration. Novel strategies have been developed to aid the delivery of mitochondria into the neuronal cell body, which in turn establishes a network with the presiding ER resulting in contact site formation. The fascinating aspect of this mechanism is that despite the lack of inherent regenerative capacity in neurons, it can be induced by modifying MERCS.}, } @article {pmid38320753, year = {2024}, author = {Khan, M and Chen, XXL and Dias, M and Santos, JR and Kour, S and You, J and van Bruggen, R and Youssef, MMM and Wan, YW and Liu, Z and Rosenfeld, JA and Tan, Q and Pandey, UB and Yalamanchili, HK and Park, J}, title = {MATR3 pathogenic variants differentially impair its cryptic splicing repression function.}, journal = {FEBS letters}, volume = {598}, number = {4}, pages = {415-436}, doi = {10.1002/1873-3468.14806}, pmid = {38320753}, issn = {1873-3468}, support = {58-3092-0-001//National Institute of Food and Agriculture/ ; //Natural Sciences and Engineering Research Council of Canada (NSERC)/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics ; Exons/genetics ; RNA-Binding Proteins/genetics/metabolism ; RNA ; Nuclear Matrix-Associated Proteins/genetics ; }, abstract = {Matrin-3 (MATR3) is an RNA-binding protein implicated in neurodegenerative and neurodevelopmental diseases. However, little is known regarding the role of MATR3 in cryptic splicing within the context of functional genes and how disease-associated variants impact this function. We show that loss of MATR3 leads to cryptic exon inclusion in many transcripts. We reveal that ALS-linked S85C pathogenic variant reduces MATR3 solubility but does not impair RNA binding. In parallel, we report a novel neurodevelopmental disease-associated M548T variant, located in the RRM2 domain, which reduces protein solubility and impairs RNA binding and cryptic splicing repression functions of MATR3. Altogether, our research identifies cryptic events within functional genes and demonstrates how disease-associated variants impact MATR3 cryptic splicing repression function.}, } @article {pmid38320749, year = {2024}, author = {Lee, I and Nandakumar, R and Haeusler, RA}, title = {Alteration of serum bile acids in amyotrophic lateral sclerosis.}, journal = {Lipids}, volume = {59}, number = {4}, pages = {85-91}, pmid = {38320749}, issn = {1558-9307}, support = {K23NS131586/NH/NIH HHS/United States ; R01 DK115825/DK/NIDDK NIH HHS/United States ; //American Brain Foundation/ ; //American Academy of Neurology/ ; ULTR001873//National Center for Advancing Translational Sciences, National Institutes of Health/ ; K23 NS131586/NS/NINDS NIH HHS/United States ; R01DK115825/NH/NIH HHS/United States ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/blood/genetics ; Male ; Female ; Middle Aged ; *Bile Acids and Salts/blood ; Case-Control Studies ; Adult ; Aged ; }, abstract = {Hydrophilic endogenous bile acids ursodeoxycholic acid (UDCA), tauroursodeoxycholic acid (TUDCA), and glucourosodeoxycholic acid (GUDCA) have suggested neuroprotective effects. We performed a case-control study to examine the association between ALS diagnosis and serum levels of bile acids. Sporadic and familial ALS patients, age- and sex-matched healthy controls, and presymptomatic gene carriers who donated blood samples were included. Non-fasted serum samples stored at -80°C were used for the analysis. Serum bile acid levels were measured by liquid chromatography-mass spectrometry (LC-MS). Concentrations of 15 bile acids were obtained, 5 non-conjugated and 10 conjugated, and compared between ALS versus control groups (presymptomatic gene carriers + healthy controls) using the Wilcoxon-Rank-Sum test. In total, 80 participants were included: 31 ALS (17 sporadic and 14 familial ALS); 49 controls (22 gene carriers, 27 healthy controls). The mean age was 50 years old and 50% were male. In the ALS group, 45% had familial disease with a pathogenic variant in C9orf72 (29%), TARDBP (10%), FUS (3%), and CHCHD10 (3%) genes. In the control group, 43% carried pathogenic variants: C9orf72 (27%), SOD1 (10%), and FUS (6%). The serum levels of UDCA, TUDCA, and GUDCA trended higher in the ALS group compared to controls (median 27 vs. 7 nM, 4 vs. 3 nM, 110 vs. 47 nM, p-values 0.04, 0.06, 0.04, respectively). No significant group differences were found in other bile acids serum levels. In conclusion, the serum level of UDCA, TUDCA, GUDCA trended higher in ALS patients compared to controls, and no evidence of deficiencies was found.}, } @article {pmid38318860, year = {2024}, author = {Jhooty, S and Barkhaus, P and Brown, A and Mascias Cadavid, J and Carter, GT and Crayle, J and Heiman-Patterson, T and Li, X and Mallon, E and Mcdermott, C and Mushannen, T and Pattee, G and Ratner, D and Wicks, P and Wiedau, M and Bedlack, R}, title = {ALSUntangled #74: Withania Somnifera (Ashwagandha).}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {25}, number = {7-8}, pages = {805-808}, doi = {10.1080/21678421.2024.2311721}, pmid = {38318860}, issn = {2167-9223}, mesh = {*Amyotrophic Lateral Sclerosis/drug therapy ; Humans ; *Withania ; Animals ; *Plant Extracts/therapeutic use ; Phytotherapy/methods ; }, abstract = {ALSUntangled reviews alternative and off-label treatments on behalf of people with ALS (PALS) who ask about them. Here, we review withania somnifera (WS) commonly known as ashwagandha or winter cherry. WS has plausible mechanisms for slowing ALS progression because of its effects on inflammation, oxidative stress, autophagy, mitochondrial function, and apoptosis. Preclinical trials demonstrate that WS slows disease progression in multiple different animal models of ALS. Of the five individuals we found who described using WS for their ALS, two individuals reported moderate benefit while none reported experiencing any significant side effects. There is currently one clinical trial using WS to treat PALS; the results are not yet published. There are no serious side effects associated with WS and the associated cost of this treatment is low. Based on the above information, WS appears to us to be a good candidate for future ALS trials.}, } @article {pmid38318827, year = {2024}, author = {Motamedy, S and Soltani, B and Kameshki, H and Kermani, AA and Amleshi, RS and Nazeri, M and Shabani, M}, title = {The Therapeutic Potential and Molecular Mechanisms Underlying the Neuroprotective Effects of Sativex[®] - A Cannabis-derived Spray.}, journal = {Mini reviews in medicinal chemistry}, volume = {24}, number = {15}, pages = {1427-1448}, pmid = {38318827}, issn = {1875-5607}, mesh = {Humans ; *Neuroprotective Agents/pharmacology/chemistry ; *Cannabidiol/pharmacology/therapeutic use/chemistry ; *Plant Extracts/chemistry/pharmacology ; *Dronabinol/pharmacology/chemistry/therapeutic use ; Animals ; Multiple Sclerosis/drug therapy ; Cannabis/chemistry ; Drug Combinations ; }, abstract = {Sativex is a cannabis-based medicine that comes in the form of an oromucosal spray. It contains equal amounts of Δ9-tetrahydrocannabinol and cannabidiol, two compounds derived from cannabis plants. Sativex has been shown to have positive effects on symptoms of amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), and sleep disorders. It also has analgesic, antiinflammatory, antitumoral, and neuroprotective properties, which make it a potential treatment option for other neurological disorders. The article reviews the results of recent preclinical and clinical studies that support the therapeutic potential of Sativex and the molecular mechanisms behind its neuroprotective benefits in various neurological disorders. The article also discusses the possible advantages and disadvantages of using Sativex as a neurotherapeutic agent, such as its safety, efficacy, availability, and legal status.}, } @article {pmid38318532, year = {2024}, author = {Geng, Y and Cai, Q}, title = {Role of C9orf72 hexanucleotide repeat expansions in ALS/FTD pathogenesis.}, journal = {Frontiers in molecular neuroscience}, volume = {17}, number = {}, pages = {1322720}, pmid = {38318532}, issn = {1662-5099}, abstract = {Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are progressive neurological disorders that share neurodegenerative pathways and features. The most prevalent genetic causes of ALS/FTD is the GGGGCC hexanucleotide repeat expansions in the first intron region of the chromosome 9 open reading frame 72 (C9orf72) gene. In this review, we comprehensively summarize the accumulating evidences elucidating the pathogenic mechanism associated with hexanucleotide repeat expansions in ALS/FTD. These mechanisms encompass the structural polymorphism of DNA and transcribed RNA, the formation of RNA foci via phase separation, and the cytoplasmic accumulation and toxicities of dipeptide-repeat proteins. Additionally, the formation of G-quadruplex structures significantly impairs the expression and normal function of the C9orf72 protein. We also discuss the sequestration of specific RNA binding proteins by GGGGCC RNA, which further contributes to the toxicity of C9orf72 hexanucleotide repeat expansions. The deeper understanding of the pathogenic mechanism of hexanucleotide repeat expansions in ALS/FTD provides multiple potential drug targets for these devastating diseases.}, } @article {pmid38318443, year = {2024}, author = {Plasencia-Salini, R and Havens, AP and Miller, KM}, title = {Biometry challenges in the longest eyes we have encountered to date.}, journal = {American journal of ophthalmology case reports}, volume = {33}, number = {}, pages = {101997}, pmid = {38318443}, issn = {2451-9936}, abstract = {PURPOSE: This report aims to present biometry challenges and solutions for a patient with the longest eyes we have encountered to date.

OBSERVATIONS: A 41-year-old woman with a history of Crouzon syndrome, extreme axial myopia, and posterior segment staphylomas was referred for cataract evaluation. Optical biometry was attempted using two partial coherence interferometry and optical low-coherence reflectometry devices that were available in 2011. Neither device could measure the axial length (AL) of either eye, unfortunately. We were able to measure them by A scan ultrasound, however, with results of 40.59 mm for the right eye and 38.29 mm for the left eye. Shortly thereafter, she underwent uncomplicated phacoemulsification with posterior chamber intraocular lens implantation under topical anesthesia. Twelve years later, she returned for repeat optical biometry with 3 newer generation devices, 2 of which utilized swept-source optical coherence tomography (SS-OCT). Only 1 SS-OCT device, the Argos biometer, was able to obtain AL measurements, and they were 40.54 mm and 40.84 mm for the right and left eyes, respectively.

CONCLUSIONS AND IMPORTANCE: Biometry measurement using optical biometers on a patient with ALs greater than 40 mm was impossible in 2011 because of the relatively short gate for acceptable readings. Ultrasound biometry can also be challenging due to the presence of posterior staphylomas. However, a newer SS-OCT with a longer AL measurement capability enabled readings to be obtained more recently.}, } @article {pmid38318390, year = {2024}, author = {Komine, O and Ohnuma, S and Hinohara, K and Hara, Y and Shimada, M and Akashi, T and Watanabe, S and Sobue, A and Kawade, N and Ogi, T and Yamanaka, K}, title = {Genetic background variation impacts microglial heterogeneity and disease progression in amyotrophic lateral sclerosis model mice.}, journal = {iScience}, volume = {27}, number = {2}, pages = {108872}, pmid = {38318390}, issn = {2589-0042}, abstract = {Recent single-cell analyses have revealed the complexity of microglial heterogeneity in brain development, aging, and neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS). Disease-associated microglia (DAMs) have been identified in ALS mice model, but their role in ALS pathology remains unclear. The effect of genetic background variations on microglial heterogeneity and functions remains unknown. Herein, we established and analyzed two mice models of ALS with distinct genetic backgrounds of C57BL/6 and BALB/c. We observed that the change in genetic background from C57BL/6 to BALB/c affected microglial heterogeneity and ALS pathology and its progression, likely due to the defective induction of neurotrophic factor-secreting DAMs and impaired microglial survival. Single-cell analyses of ALS mice revealed new markers for each microglial subtype and a possible association between microglial heterogeneity and systemic immune environments. Thus, we highlighted the role of microglia in ALS pathology and importance of genetic background variations in modulating microglial functions.}, } @article {pmid38318246, year = {2024}, author = {Izquierdo-Condoy, JS and Arias Rodríguez, FD and Duque-Sánchez, E and Alegría N, N and Rojas Cadena, M and Naranjo-Lara, P and Mendoza, AP and Jima-Sanmartín, J and Casanova, DA and García, B and Giraldo, NC}, title = {Assessment of preparedness and proficiency in basic and advanced life support among nursing professionals: a cross-sectional study.}, journal = {Frontiers in medicine}, volume = {11}, number = {}, pages = {1328573}, pmid = {38318246}, issn = {2296-858X}, abstract = {BACKGROUND: Cardiac diseases are among the leading causes of death worldwide, including sudden cardiac arrest in particular. Nursing professionals are often the first to encounter these scenarios in various settings. Adequate preparation and competent knowledge among nurses significantly impact survival rates positively.

AIM: To describe the state of knowledge about Basic and Advanced Life Support guidelines among Ecuadorian nursing professionals.

METHODOLOGY: A nationwide, descriptive, cross-sectional study was conducted from February to April 2023 among Ecuadorian nursing professionals. Participants were invited through official social media groups such as WhatsApp and Facebook. The study utilized a self-administered online questionnaire to evaluate theoretical knowledge of Basic Life Support (BLS) and Advanced Life Support (ALS). Knowledge scores were assigned based on the number of correct answers on the tests. T-tests and one-way ANOVA were used to examine relationships between knowledge scores and demographic and academic training variables.

RESULTS: A total of 217 nursing professionals participated in the study. The majority of the participants were female (77.4%) and held a university degree (79.9%). Among them, only 44.7% claimed to have obtained a BLS training certificate at least once, and 19.4% had ALS certification. The overall BLS knowledge score (4.8/10 ± 1.8 points) was higher than the ALS score (4.3/10 ± 1.8 points). Participants who had obtained BLS certification and those who used evidence-based summaries as a source of extracurricular training achieved higher BLS and ALS knowledge scores.

CONCLUSION: Ecuadorian nursing professionals in this study exhibited a significant deficiency in theoretical knowledge of BLS and ALS. Formal training and preparation positively impact life support knowledge. Support and inclusion of Ecuadorian nurses in training and academic preparation programs beginning at the undergraduate level are essential for promoting life support knowledge and improving outcomes.}, } @article {pmid38317984, year = {2024}, author = {Harvey, C and Weinreich, M and Lee, JAK and Shaw, AC and Ferraiuolo, L and Mortiboys, H and Zhang, S and Hop, PJ and Zwamborn, RAJ and van Eijk, K and Julian, TH and Moll, T and Iacoangeli, A and Al Khleifat, A and Quinn, JP and Pfaff, AL and Kõks, S and Poulton, J and Battle, SL and Arking, DE and Snyder, MP and , and Veldink, JH and Kenna, KP and Shaw, PJ and Cooper-Knock, J}, title = {Rare and common genetic determinants of mitochondrial function determine severity but not risk of amyotrophic lateral sclerosis.}, journal = {Heliyon}, volume = {10}, number = {3}, pages = {e24975}, pmid = {38317984}, issn = {2405-8440}, support = {S10 OD025212/OD/NIH HHS/United States ; R56 NS073873/NS/NINDS NIH HHS/United States ; R01 NS073873/NS/NINDS NIH HHS/United States ; R01 HL101388/HL/NHLBI NIH HHS/United States ; P50 HL083800/HL/NHLBI NIH HHS/United States ; P30 DK116074/DK/NIDDK NIH HHS/United States ; R01 HL122939/HL/NHLBI NIH HHS/United States ; UM1 HG009442/HG/NHGRI NIH HHS/United States ; /WT_/Wellcome Trust/United Kingdom ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease involving selective vulnerability of energy-intensive motor neurons (MNs). It has been unclear whether mitochondrial function is an upstream driver or a downstream modifier of neurotoxicity. We separated upstream genetic determinants of mitochondrial function, including genetic variation within the mitochondrial genome or autosomes; from downstream changeable factors including mitochondrial DNA copy number (mtCN). Across three cohorts including 6,437 ALS patients, we discovered that a set of mitochondrial haplotypes, chosen because they are linked to measurements of mitochondrial function, are a determinant of ALS survival following disease onset, but do not modify ALS risk. One particular haplotype appeared to be neuroprotective and was significantly over-represented in two cohorts of long-surviving ALS patients. Causal inference for mitochondrial function was achievable using mitochondrial haplotypes, but not autosomal SNPs in traditional Mendelian randomization (MR). Furthermore, rare loss-of-function genetic variants within, and reduced MN expression of, ACADM and DNA2 lead to ∼50 % shorter ALS survival; both proteins are implicated in mitochondrial function. Both mtCN and cellular vulnerability are linked to DNA2 function in ALS patient-derived neurons. Finally, MtCN responds dynamically to the onset of ALS independently of mitochondrial haplotype, and is correlated with disease severity. We conclude that, based on the genetic measures we have employed, mitochondrial function is a therapeutic target for amelioration of disease severity but not prevention of ALS.}, } @article {pmid38317639, year = {2024}, author = {Verma, S and Vats, A and Ahuja, V and Vats, K and Khurana, S and Vats, Y and Gourie-Devi, M and Wajid, S and Ganguly, NK and Chakraborti, P and Taneja, V}, title = {Functional consequences of familial ALS-associated SOD1[L84F] in neuronal and muscle cells.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {38}, number = {3}, pages = {e23461}, doi = {10.1096/fj.202301979R}, pmid = {38317639}, issn = {1530-6860}, support = {09/591(0150)/2018-EMR-I//Council of Scientific and Industrial Research, India (CSIR)/ ; 3/1/2/151/Neuro/2021-NCD-I//Indian Council of Medical Research (ICMR)/ ; 2020-2641/CMB/ADHOC-BMS//Indian Council of Medical Research (ICMR)/ ; 211610027970//University Grants Commission (UGC)/ ; }, mesh = {Animals ; Mice ; *Amyotrophic Lateral Sclerosis/genetics/metabolism ; Disease Models, Animal ; Mice, Transgenic ; Muscle Cells/metabolism ; Mutation ; *Superoxide Dismutase-1/genetics ; }, abstract = {Amyotrophic lateral sclerosis is a fatal neurodegenerative disorder characterized by progressive skeletal muscle denervation and loss of motor neurons that results in muscle atrophy and eventual death due to respiratory failure. Previously, we identified a novel SOD1[L84F] variation in a familial ALS case. In this study, we examined the functional consequences of SOD1[L84F] overexpression in the mouse motor neuron cell line (NSC-34). The cells expressing SOD1[L84F] showed increased oxidative stress and increased cell death. Interestingly, SOD1[L84F] destabilized the native dimer and formed high molecular weight SDS-resistant protein aggregates. Furthermore, SOD1[L84F] also decreased the percentage of differentiated cells and significantly reduced neurite length. A plethora of evidence suggested active involvement of skeletal muscle in disease initiation and progression. We observed differential processing of the mutant SOD1 and perturbations of cellular machinery in NSC-34 and muscle cell line C2C12. Unlike neuronal cells, mutant protein failed to accumulate in muscle cells probably due to the activated autophagy, as evidenced by increased LC3-II and reduced p62. Further, SOD1[L84F] altered mitochondrial dynamics only in NSC-34. In addition, microarray analysis also revealed huge variations in differentially expressed genes between NSC-34 and C2C12. Interestingly, SOD1[L84F] hampered the endogenous FUS autoregulatory mechanism in NSC-34 by downregulating retention of introns 6 and 7 resulting in a two-fold upregulation of FUS. No such changes were observed in C2C12. Our findings strongly suggest the differential processing and response towards the mutant SOD1 in neuronal and muscle cell lines.}, } @article {pmid38317225, year = {2024}, author = {Liddell, JR and Hilton, JBW and Kysenius, K and Billings, JL and Nikseresht, S and McInnes, LE and Hare, DJ and Paul, B and Mercer, SW and Belaidi, AA and Ayton, S and Roberts, BR and Beckman, JS and McLean, CA and White, AR and Donnelly, PS and Bush, AI and Crouch, PJ}, title = {Microglial ferroptotic stress causes non-cell autonomous neuronal death.}, journal = {Molecular neurodegeneration}, volume = {19}, number = {1}, pages = {14}, pmid = {38317225}, issn = {1750-1326}, mesh = {Mice ; Animals ; Humans ; Microglia/metabolism ; *Amyotrophic Lateral Sclerosis/metabolism ; Superoxide Dismutase-1/metabolism ; *Neurodegenerative Diseases/metabolism ; Cell Death ; Disease Models, Animal ; }, abstract = {BACKGROUND: Ferroptosis is a form of regulated cell death characterised by lipid peroxidation as the terminal endpoint and a requirement for iron. Although it protects against cancer and infection, ferroptosis is also implicated in causing neuronal death in degenerative diseases of the central nervous system (CNS). The precise role for ferroptosis in causing neuronal death is yet to be fully resolved.

METHODS: To elucidate the role of ferroptosis in neuronal death we utilised co-culture and conditioned medium transfer experiments involving microglia, astrocytes and neurones. We ratified clinical significance of our cell culture findings via assessment of human CNS tissue from cases of the fatal, paralysing neurodegenerative condition of amyotrophic lateral sclerosis (ALS). We utilised the SOD1[G37R] mouse model of ALS and a CNS-permeant ferroptosis inhibitor to verify pharmacological significance in vivo.

RESULTS: We found that sublethal ferroptotic stress selectively affecting microglia triggers an inflammatory cascade that results in non-cell autonomous neuronal death. Central to this cascade is the conversion of astrocytes to a neurotoxic state. We show that spinal cord tissue from human cases of ALS exhibits a signature of ferroptosis that encompasses atomic, molecular and biochemical features. Further, we show the molecular correlation between ferroptosis and neurotoxic astrocytes evident in human ALS-affected spinal cord is recapitulated in the SOD1[G37R] mouse model where treatment with a CNS-permeant ferroptosis inhibitor, Cu[II](atsm), ameliorated these markers and was neuroprotective.

CONCLUSIONS: By showing that microglia responding to sublethal ferroptotic stress culminates in non-cell autonomous neuronal death, our results implicate microglial ferroptotic stress as a rectifiable cause of neuronal death in neurodegenerative disease. As ferroptosis is currently primarily regarded as an intrinsic cell death phenomenon, these results introduce an entirely new pathophysiological role for ferroptosis in disease.}, } @article {pmid38316966, year = {2024}, author = {Naruse, H and Ishiura, H and Esaki, K and Mitsui, J and Satake, W and Greimel, P and Shingai, N and Machino, Y and Kokubo, Y and Hamaguchi, H and Oda, T and Ikkaku, T and Yokota, I and Takahashi, Y and Suzuki, Y and Matsukawa, T and Goto, J and Koh, K and Takiyama, Y and Morishita, S and Yoshikawa, T and Tsuji, S and Toda, T}, title = {SPTLC2 variants are associated with early-onset ALS and FTD due to aberrant sphingolipid synthesis.}, journal = {Annals of clinical and translational neurology}, volume = {11}, number = {4}, pages = {946-957}, pmid = {38316966}, issn = {2328-9503}, support = {21K07512//Japan Society for the Promotion of Science/ ; 22K15724//Japan Society for the Promotion of Science/ ; //Ministry of Health, Labour and Welfare/ ; JP22ek0109617//Japan Agency for Medical Research and Development/ ; JP23ek0109617//Japan Agency for Medical Research and Development/ ; }, mesh = {Adult ; Humans ; *Frontotemporal Dementia/genetics ; *Amyotrophic Lateral Sclerosis/genetics ; Serine C-Palmitoyltransferase/genetics ; *Neurodegenerative Diseases ; Sphingolipids ; Ceramides ; }, abstract = {OBJECTIVE: Amyotrophic lateral sclerosis (ALS) is a devastating, incurable neurodegenerative disease. A subset of ALS patients manifests with early-onset and complex clinical phenotypes. We aimed to elucidate the genetic basis of these cases to enhance our understanding of disease etiology and facilitate the development of targeted therapies.

METHODS: Our research commenced with an in-depth genetic and biochemical investigation of two specific families, each with a member diagnosed with early-onset ALS (onset age of <40 years). This involved whole-exome sequencing, trio analysis, protein structure analysis, and sphingolipid measurements. Subsequently, we expanded our analysis to 62 probands with early-onset ALS and further included 440 patients with adult-onset ALS and 1163 healthy controls to assess the prevalence of identified genetic variants.

RESULTS: We identified heterozygous variants in the serine palmitoyltransferase long chain base subunit 2 (SPTLC2) gene in patients with early-onset ALS. These variants, located in a region closely adjacent to ORMDL3, bear similarities to SPTLC1 variants previously implicated in early-onset ALS. Patients with ALS carrying these SPTLC2 variants displayed elevated plasma ceramide levels, indicative of increased serine palmitoyltransferase (SPT) activity leading to sphingolipid overproduction.

INTERPRETATION: Our study revealed novel SPTLC2 variants in patients with early-onset ALS exhibiting frontotemporal dementia. The combination of genetic evidence and the observed elevation in plasma ceramide levels establishes a crucial link between dysregulated sphingolipid metabolism and ALS pathogenesis. These findings expand our understanding of ALS's genetic diversity and highlight the distinct roles of gene defects within SPT subunits in its development.}, } @article {pmid38316400, year = {2024}, author = {Taule, T and Tysnes, OB and Aßmus, J and Rekand, T}, title = {A prospective study for using cognitive decline as a predictor for survival and use of feeding/respiratory support for patients with motor neuron disease in Norway.}, journal = {Annals of palliative medicine}, volume = {13}, number = {1}, pages = {86-92}, doi = {10.21037/apm-23-386}, pmid = {38316400}, issn = {2224-5839}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy ; Prospective Studies ; *Motor Neuron Disease/complications/therapy ; *Cognitive Dysfunction ; Enteral Nutrition ; }, abstract = {BACKGROUND: There is a need for knowledge regarding the medical management of motor neuron disease/amyotrophic lateral sclerosis (MND/ALS) with and without cognitive decline. It has scarcely been studied whether cognitive decline will influence the course of disease or interfere with the use of life-prolonging aids for respiration and nutrition. Cognitive decline may impact the length of illness.

METHODS: Patients were prospectively recruited from an ALS outpatient clinic at Haukeland University Hospital. Participants underwent the standardized cognitive test Edinburgh Cognitive and Behavioral ALS Screen Norwegian version (ECAS-N), clinical examination, and were functionally assessed by the ALS Functioning Rating Scale-revised version (ALS-FRS-R). The time and indication for installation of a feeding tube [percutaneous endoscopic gastrostomy (PEG)] and/or respiratory aid [bilevel positive airway pressure device (BiPAP)] or invasive respirator were retrieved from the medical records. Kaplan-Meier tests were used to study the risk of death and the probability for implementing PEG and/or BiPAP in relation to time from diagnosis. The individual assessment was used for analyzing the establishment of aids in relation to point of death.

RESULTS: A total of 40 patients were evaluated for the study, 31 of whom were finally included. None of the included patients did not use an invasive respirator. The patients were divided into two subgroups (normal cognition or cognitive decline, cut-off 92 points) according to their performance in the ECAS-N. The course of the disease, shown as a risk of death, was higher among the ALS/MND patients with cognitive decline compared to those with cognitive intact function throughout the study period. The cognitive status did not influence the fitting of aids. Use of aids did not influence the survival in subgroups significantly.

CONCLUSIONS: The study demonstrated shorter survival for the patients with ALS/MND with cognitive decline compared to those without cognitive decline. The practice and implementation of both BiPAP and PEG did not differ among the ALS/MND patients with and without cognitive decline in Norway.}, } @article {pmid38314348, year = {2023}, author = {Watts, ME and Giadone, RM and Ordureau, A and Holton, KM and Harper, JW and Rubin, LL}, title = {Analyzing the ER stress response in ALS patient derived motor neurons identifies druggable neuroprotective targets.}, journal = {Frontiers in cellular neuroscience}, volume = {17}, number = {}, pages = {1327361}, pmid = {38314348}, issn = {1662-5102}, support = {F32 AG079593/AG/NIA NIH HHS/United States ; R01 NS083524/NS/NINDS NIH HHS/United States ; R01 NS110395/NS/NINDS NIH HHS/United States ; R37 NS083524/NS/NINDS NIH HHS/United States ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a degenerative motor neuron (MN) disease with severely limited treatment options. Identification of effective treatments has been limited in part by the lack of predictive animal models for complex human disorders. Here, we utilized pharmacologic ER stressors to exacerbate underlying sensitivities conferred by ALS patient genetics in induced pluripotent stem cell (iPSC)-derived motor neurons (MNs). In doing so, we found that thapsigargin and tunicamycin exposure recapitulated ALS-associated degeneration, and that we could rescue this degeneration via MAP4K4 inhibition (MAP4K4i). We subsequently identified mechanisms underlying MAP4K4i-mediated protection by performing phosphoproteomics on iPSC-derived MNs treated with ER stressors ±MAP4K4i. Through these analyses, we found JNK, PKC, and BRAF to be differentially modulated in MAP4K4i-protected MNs, and that inhibitors to these proteins could also rescue MN toxicity. Collectively, this study highlights the value of utilizing ER stressors in ALS patient MNs to identify novel druggable targets.}, } @article {pmid38314277, year = {2024}, author = {Mohan, S and Alhazmi, HA and Hassani, R and Khuwaja, G and Maheshkumar, VP and Aldahish, A and Chidambaram, K}, title = {Role of ferroptosis pathways in neuroinflammation and neurological disorders: From pathogenesis to treatment.}, journal = {Heliyon}, volume = {10}, number = {3}, pages = {e24786}, pmid = {38314277}, issn = {2405-8440}, abstract = {Ferroptosis is a newly discovered non-apoptotic and iron-dependent type of cell death. Ferroptosis mainly takes place owing to the imbalance of anti-oxidation and oxidation in the body. It is regulated via a number of factors and pathways both inside and outside the cell. Ferroptosis is closely linked with brain and various neurological disorders (NDs). In the human body, the brain contains the highest levels of polyunsaturated fatty acids, which are known as lipid peroxide precursors. In addition, there is also a connection of glutathione depletion and lipid peroxidation with NDs. There is growing evidence regarding the possible link between neuroinflammation and multiple NDs, such as Alzheimer's disease, amyotrophic lateral sclerosis, Parkinson's disease, Huntington's disease, and stroke. Recent studies have demonstrated that disruptions of lipid reactive oxygen species (ROS), glutamate excitatory toxicity, iron homeostasis, and various other manifestations linked with ferroptosis can be identified in various neuroinflammation-mediated NDs. It has also been reported that damage-associated molecular pattern molecules including ROS are generated during the events of ferroptosis and can cause glial activation via activating neuroimmune pathways, which subsequently leads to the generation of various inflammatory factors that play a role in various NDs. This review summarizes the regulation pathways of ferroptosis, the link between ferroptosis as well as inflammation in NDs, and the potential of a range of therapeutic agents that can be used to target ferroptosis and inflammation in the treatment of neurological disorders.}, } @article {pmid38313873, year = {2024}, author = {Hill, J and Sanghani, N and Li, Y}, title = {Features Suggestive of Coexisting Amyotrophic Lateral Sclerosis in Patients With Spinal Stenosis and Influence of Spinal Decompression.}, journal = {Cureus}, volume = {16}, number = {1}, pages = {e51587}, pmid = {38313873}, issn = {2168-8184}, abstract = {BACKGROUND: Spinal stenosis and amyotrophic lateral sclerosis (ALS) can co-occur and both manifest as signs of dysfunction of lower and/or upper motor neurons. Few studies have identified factors that alert the diagnosis of ALS in patients with spinal stenosis, and the influence of spinal decompression surgery on ALS progression remains unclear.

OBJECTIVE: The objective of this study is to describe factors that are suggestive of an ALS diagnosis in patients with spinal stenosis and influence of spinal decompression surgery on the progression of ALS  Materials and methods: A retrospective review of the institutional ALS database and electronic medical records was performed to identify patients with coexisting diagnoses of ALS and moderate to severe cervical and/or lumbosacral spine stenosis. Identified patients were divided into two subgroups: those with spinal decompression surgery and those without. Comparisons of clinical features and progression of ALS were made between subgroups.

RESULTS:  A total of 77 patients with ALS and coexisting moderate to severe cervical or lumbosacral spine stenosis were included. Among them, 50 patients underwent spinal decompression surgery and 27 did not. In comparison to patients with spinal decompression, patients without spinal decompression surgery were seen more frequently by neurologists (74% versus 26%), had less prominent radicular pain (19% versus 50%), demonstrated more frequent bulbar signs (30% versus 8%), experienced more likely weight loss (41% versus 4%), and disclosed more noticeable axonal loss changes on electromyography. Spinal decompression surgery did not modify the progression of ALS based on ALSFRS-R score change and analysis of survival duration.

CONCLUSION: Our study identified a number of useful features that are suggestive of an ALS diagnosis when evaluating patients with spinal stenosis and may support the performance of spinal decompression surgery in a subset of selected ALS patients with symptomatic spinal stenosis.}, } @article {pmid38313408, year = {2023}, author = {Monov, D and Molodozhnikova, N}, title = {Biochemical parameters as a tool to assess the nutritional status of patients with amyotrophic lateral sclerosis.}, journal = {Frontiers in neurology}, volume = {14}, number = {}, pages = {1258224}, pmid = {38313408}, issn = {1664-2295}, abstract = {BACKGROUND: The research aimed to analyze blood biochemical parameters in patients with amyotrophic lateral sclerosis and to determine whether they can be used to assess their nutritional status.

METHODS: The study included 45 patients diagnosed with amyotrophic lateral sclerosis (ALS): 28 (62.2%) were men and 17 (37.8%) were women. The mean age of the study participants was 50.69 ± 7.24 years. The control group consisted of 30 practically healthy individuals.

RESULTS: Compared with practically healthy individuals, patients with ALS had significantly lower blood parameters, including total lymphocyte count (1.49 ± 0.11 vs. 2.86 ± 0.25, p < 0.05), total protein (60.55 ± 2.38 vs. 77.80 ± 4.41, p < 0.05), albumin (33.70 ± 2.03 vs. 46.49 ± 3.22, p < 0.05), urea (3.09 ± 0.36 vs. 5.37 ± 0.50, p < 0.05), creatinine (51.28 ± 4.42 vs. 70.91 ± 5.13, p < 0.05), and transferrin (1.84 ± 0.12 vs. 2.32 ± 0.10, p < 0.05). These parameters correspond to first-degree malnutrition. There were direct correlations between anthropometric and biochemical parameters in the ALS group. BMI correlated with the blood levels of total protein (r = 0.22, p < 0.05), albumin (r = 0.27, p < 0.05), urea (r = 0.33, p < 0.05), creatinine (r = 0.30, p < 0.05), transferrin (r = 0.18, p < 0.05), and total lymphocyte count (r = 0.20, p < 0.05). PNI correlated with the blood levels of total protein (r = 0.53, p < 0.05), albumin (r = 0.87, p < 0.05), total cholesterol (r = 0.34, p < 0.05), transferrin (r = 0.40, p < 0.05), total lymphocyte count (r = 0.79, p < 0.05), urea (r = 0, 37, p < 0.05), and creatinine (r = 0.32, p < 0.05).

CONCLUSION: The study presents compelling evidence supporting the utilization of biochemical parameters, including total protein, albumin, urea, creatinine, transferrin, and total lymphocyte count, for potentially evaluating the nutritional status of individuals diagnosed with ALS.}, } @article {pmid38313254, year = {2024}, author = {Bryce-Smith, S and Brown, AL and Mehta, PR and Mattedi, F and Mikheenko, A and Barattucci, S and Zanovello, M and Dattilo, D and Yome, M and Hill, SE and Qi, YA and Wilkins, OG and Sun, K and Ryadnov, E and Wan, Y and , and Vargas, JNS and Birsa, N and Raj, T and Humphrey, J and Keuss, M and Ward, M and Secrier, M and Fratta, P}, title = {TDP-43 loss induces extensive cryptic polyadenylation in ALS/FTD.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {38313254}, issn = {2692-8205}, support = {/WT_/Wellcome Trust/United Kingdom ; MC_PC_MR/S022708/1/MRC_/Medical Research Council/United Kingdom ; MR/S006508/1/MRC_/Medical Research Council/United Kingdom ; U54 NS123743/NS/NINDS NIH HHS/United States ; }, abstract = {Nuclear depletion and cytoplasmic aggregation of the RNA-binding protein TDP-43 is the hallmark of ALS, occurring in over 97% of cases. A key consequence of TDP-43 nuclear loss is the de-repression of cryptic exons. Whilst TDP-43 regulated cryptic splicing is increasingly well catalogued, cryptic alternative polyadenylation (APA) events, which define the 3' end of last exons, have been largely overlooked, especially when not associated with novel upstream splice junctions. We developed a novel bioinformatic approach to reliably identify distinct APA event types: alternative last exons (ALE), 3'UTR extensions (3'Ext) and intronic polyadenylation (IPA) events. We identified novel neuronal cryptic APA sites induced by TDP-43 loss of function by systematically applying our pipeline to a compendium of publicly available and in house datasets. We find that TDP-43 binding sites and target motifs are enriched at these cryptic events and that TDP-43 can have both repressive and enhancing action on APA. Importantly, all categories of cryptic APA can also be identified in ALS and FTD post mortem brain regions with TDP-43 proteinopathy underlining their potential disease relevance. RNA-seq and Ribo-seq analyses indicate that distinct cryptic APA categories have different downstream effects on transcript and translation. Intriguingly, cryptic 3'Exts occur in multiple transcription factors, such as ELK1, SIX3, and TLX1, and lead to an increase in wild-type protein levels and function. Finally, we show that an increase in RNA stability leading to a higher cytoplasmic localisation underlies these observations. In summary, we demonstrate that TDP-43 nuclear depletion induces a novel category of cryptic RNA processing events and we expand the palette of TDP-43 loss consequences by showing this can also lead to an increase in normal protein translation.}, } @article {pmid38312023, year = {2024}, author = {Stoccoro, A and Smith, AR and Mosca, L and Marocchi, A and Gerardi, F and Lunetta, C and Lunnon, K and Migliore, L and Coppedè, F}, title = {Mitochondrial D-loop methylation levels inversely correlate with disease duration in amyotrophic lateral sclerosis.}, journal = {Epigenomics}, volume = {16}, number = {4}, pages = {203-214}, doi = {10.2217/epi-2023-0265}, pmid = {38312023}, issn = {1750-192X}, support = {Researcher's intramural funds (ATENEO Funds, Uni)//Università di Pisa/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics ; Mutation ; DNA Methylation ; DNA, Mitochondrial/genetics ; Mitochondria/genetics ; }, abstract = {Aim: To correlate mitochondrial D-loop region methylation levels and mtDNA copy number with disease duration in familial amyotrophic lateral sclerosis (ALS) patients. Patients & methods: The study population included 12 ALS patients with a mutation in SOD1 and 13 ALS patients with the C9orf72 hexanucleotide repeat expansion. Methylation levels of the D-loop region and mtDNA copy number were quantified using pyrosequencing and quantitative PCR, respectively. Results: We observed that D-loop methylation levels inversely correlated while mtDNA copy number positively correlated with disease duration. Conclusion: Considering the central role played by mitochondria in ALS, this preliminary study provides new knowledge for future studies aimed at identifying biomarkers of disease progression and new targets for therapeutic interventions.}, } @article {pmid38311779, year = {2024}, author = {Ueda, T and Takeuchi, T and Fujikake, N and Suzuki, M and Minakawa, EN and Ueyama, M and Fujino, Y and Kimura, N and Nagano, S and Yokoseki, A and Onodera, O and Mochizuki, H and Mizuno, T and Wada, K and Nagai, Y}, title = {Dysregulation of stress granule dynamics by DCTN1 deficiency exacerbates TDP-43 pathology in Drosophila models of ALS/FTD.}, journal = {Acta neuropathologica communications}, volume = {12}, number = {1}, pages = {20}, pmid = {38311779}, issn = {2051-5960}, support = {21H02840//Japan Society for the Promotion of Science/ ; 22H02792//Japan Society for the Promotion of Science/ ; 24659438//Japan Society for the Promotion of Science/ ; 17H05699//Japan Society for the Promotion of Science/ ; 20H05927//Japan Society for the Promotion of Science/ ; 11013026//Japan Society for the Promotion of Science/ ; JP15dm0107026//Japan Agency for Medical Research and Development/ ; JP20dm0107061//Japan Agency for Medical Research and Development/ ; JP16ek0109018//Japan Agency for Medical Research and Development/ ; JP19ek0109222//Japan Agency for Medical Research and Development/ ; JP20ek0109316//Japan Agency for Medical Research and Development/ ; JPMJPR17H8//Precursory Research for Embryonic Science and Technology/ ; RGY0066/2017//Human Frontier Science Program/ ; }, mesh = {Animals ; Humans ; *Amyotrophic Lateral Sclerosis/pathology ; *DNA-Binding Proteins/genetics/metabolism ; Drosophila/metabolism ; *Dynactin Complex/genetics ; *Frontotemporal Dementia/pathology ; Stress Granules ; *Drosophila Proteins/genetics ; }, abstract = {The abnormal aggregation of TDP-43 into cytoplasmic inclusions in affected neurons is a major pathological hallmark of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Although TDP-43 is aberrantly accumulated in the neurons of most patients with sporadic ALS/FTD and other TDP-43 proteinopathies, how TDP-43 forms cytoplasmic aggregates remains unknown. In this study, we show that a deficiency in DCTN1, a subunit of the microtubule-associated motor protein complex dynactin, perturbs the dynamics of stress granules and drives the formation of TDP-43 cytoplasmic aggregation in cultured cells, leading to the exacerbation of TDP-43 pathology and neurodegeneration in vivo. We demonstrated using a Drosophila model of ALS/FTD that genetic knockdown of DCTN1 accelerates the formation of ubiquitin-positive cytoplasmic inclusions of TDP-43. Knockdown of components of other microtubule-associated motor protein complexes, including dynein and kinesin, also increased the formation of TDP-43 inclusions, indicating that intracellular transport along microtubules plays a key role in TDP-43 pathology. Notably, DCTN1 knockdown delayed the disassembly of stress granules in stressed cells, leading to an increase in the formation of pathological cytoplasmic inclusions of TDP-43. Our results indicate that a deficiency in DCTN1, as well as disruption of intracellular transport along microtubules, is a modifier that drives the formation of TDP-43 pathology through the dysregulation of stress granule dynamics.}, } @article {pmid38311731, year = {2024}, author = {Simmatis, LER and Robin, J and Spilka, MJ and Yunusova, Y}, title = {Detecting bulbar amyotrophic lateral sclerosis (ALS) using automatic acoustic analysis.}, journal = {Biomedical engineering online}, volume = {23}, number = {1}, pages = {15}, pmid = {38311731}, issn = {1475-925X}, support = {R01 DC013547/DC/NIDCD NIH HHS/United States ; R01DC013547/NH/NIH HHS/United States ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis ; Bayes Theorem ; Speech ; Speech Disorders/diagnosis ; ROC Curve ; }, abstract = {Automatic speech assessments have the potential to dramatically improve ALS clinical practice and facilitate patient stratification for ALS clinical trials. Acoustic speech analysis has demonstrated the ability to capture a variety of relevant speech motor impairments, but implementation has been hindered by both the nature of lab-based assessments (requiring travel and time for patients) and also by the opacity of some acoustic feature analysis methods. These challenges and others have obscured the ability to distinguish different ALS disease stages/severities. Validation of automated acoustic analysis tools could enable detection of early signs of ALS, and these tools could be deployed to screen and monitor patients without requiring clinic visits. Here, we sought to determine whether acoustic features gathered using an automated assessment app could detect ALS as well as different levels of speech impairment severity resulting from ALS. Speech samples (readings of a standardized, 99-word passage) from 119 ALS patients with varying degrees of disease severity as well as 22 neurologically healthy participants were analyzed, and 53 acoustic features were extracted. Patients were stratified into early and late stages of disease (ALS-early/ALS-E and ALS-late/ALS-L) based on the ALS Functional Ratings Scale-Revised bulbar score (FRS-bulb) (median [interquartile range] of FRS-bulbar scores: 11[3]). The data were analyzed using a sparse Bayesian logistic regression classifier. It was determined that the current relatively small set of acoustic features could distinguish between ALS and controls well (area under receiver-operating characteristic curve/AUROC = 0.85), that the ALS-E patients could be separated well from control participants (AUROC = 0.78), and that ALS-E and ALS-L patients could be reasonably separated (AUROC = 0.70). These results highlight the potential for automated acoustic analyses to detect and stratify ALS.}, } @article {pmid38311174, year = {2024}, author = {Demongin, C and Tranier, S and Joshi, V and Ceschi, L and Desforges, B and Pastré, D and Hamon, L}, title = {RNA and the RNA-binding protein FUS act in concert to prevent TDP-43 spatial segregation.}, journal = {The Journal of biological chemistry}, volume = {300}, number = {3}, pages = {105716}, pmid = {38311174}, issn = {1083-351X}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism ; *DNA-Binding Proteins/genetics/metabolism ; Peptide Fragments/metabolism ; *RNA/metabolism ; RNA, Messenger/genetics/metabolism ; *RNA-Binding Protein FUS/genetics/metabolism ; }, abstract = {FUS and TDP-43 are two self-adhesive aggregation-prone mRNA-binding proteins whose pathological mutations have been linked to neurodegeneration. While TDP-43 and FUS form reversible mRNA-rich compartments in the nucleus, pathological mutations promote their respective cytoplasmic aggregation in neurons with no apparent link between the two proteins except their intertwined function in mRNA processing. By combining analyses in cellular context and at high resolution in vitro, we unraveled that TDP-43 is specifically recruited in FUS assemblies to form TDP-43-rich subcompartments but without reciprocity. The presence of mRNA provides an additional scaffold to promote the mixing between TDP-43 and FUS. Accordingly, we also found that the pathological truncated form of TDP-43, TDP-25, which has an impaired RNA-binding ability, no longer mixes with FUS. Together, these results suggest that the binding of FUS along nascent mRNAs enables TDP-43, which is highly aggregation-prone, to mix with FUS phase to form mRNA-rich subcompartments. A functional link between FUS and TDP-43 may explain their common implication in amyotrophic lateral sclerosis.}, } @article {pmid38309276, year = {2024}, author = {Ku, J and Lee, K and Ku, D and Kim, S and Lee, J and Bang, H and Kim, N and Do, H and Lee, H and Lim, C and Han, J and Lee, YS and Kim, Y}, title = {Alternative polyadenylation determines the functional landscape of inverted Alu repeats.}, journal = {Molecular cell}, volume = {84}, number = {6}, pages = {1062-1077.e9}, doi = {10.1016/j.molcel.2024.01.008}, pmid = {38309276}, issn = {1097-4164}, mesh = {Humans ; Mice ; Animals ; *Tumor Suppressor Protein p53/genetics ; *Polyadenylation ; 3' Untranslated Regions/genetics ; Gene Expression Regulation ; Introns ; }, abstract = {Inverted Alu repeats (IRAlus) are abundantly found in the transcriptome, especially in introns and 3' untranslated regions (UTRs). Yet, the biological significance of IRAlus embedded in 3' UTRs remains largely unknown. Here, we find that 3' UTR IRAlus silences genes involved in essential signaling pathways. We utilize J2 antibody to directly capture and map the double-stranded RNA structure of 3' UTR IRAlus in the transcriptome. Bioinformatic analysis reveals alternative polyadenylation as a major axis of IRAlus-mediated gene regulation. Notably, the expression of mouse double minute 2 (MDM2), an inhibitor of p53, is upregulated by the exclusion of IRAlus during UTR shortening, which is exploited to silence p53 during tumorigenesis. Moreover, the transcriptome-wide UTR lengthening in neural progenitor cells results in the global downregulation of genes associated with neurodegenerative diseases, including amyotrophic lateral sclerosis, via IRAlus inclusion. Our study establishes the functional landscape of 3' UTR IRAlus and its role in human pathophysiology.}, } @article {pmid38308916, year = {2024}, author = {Pietrobon, D and Conti, F}, title = {Astrocytic Na[+], K[+] ATPases in physiology and pathophysiology.}, journal = {Cell calcium}, volume = {118}, number = {}, pages = {102851}, doi = {10.1016/j.ceca.2024.102851}, pmid = {38308916}, issn = {1532-1991}, mesh = {Humans ; Mice ; Animals ; Sodium-Potassium-Exchanging ATPase/genetics/metabolism ; *Migraine with Aura/genetics/metabolism ; Astrocytes/metabolism ; *Alzheimer Disease/metabolism ; *Amyotrophic Lateral Sclerosis/genetics/metabolism ; }, abstract = {The Na[+], K[+] ATPases play a fundamental role in the homeostatic functions of astrocytes. After a brief historic prologue and discussion of the subunit composition and localization of the astrocytic Na[+], K[+] ATPases, the review focuses on the role of the astrocytic Na[+], K[+] pumps in extracellular K[+] and glutamate homeostasis, intracellular Na[+] and Ca[2+] homeostasis and signaling, regulation of synaptic transmission and neurometabolic coupling between astrocytes and neurons. Loss-of-function mutations in the gene encoding the astrocytic α2 Na[+], K[+] ATPase cause a rare monogenic form of migraine with aura (familial hemiplegic migraine type 2). On the other hand, the α2 Na[+], K[+] ATPase is upregulated in spinal cord and brain samples from amyotrophic lateral sclerosis and Alzheimer disease patients, respectively. In the last part, the review focuses on i) the migraine relevant phenotypes shown by familial hemiplegic migraine type 2 knock-in mice with 50 % reduced expression of the astrocytic α2 Na[+], K[+] ATPase and the insights into the pathophysiology of migraine obtained from these genetic mouse models, and ii) the evidence that upregulation of the astrocytic α2 Na[+], K[+] ATPase in mouse models of amyotrophic lateral sclerosis and Alzheimer disease promotes neuroinflammation and contributes to progressive neurodegeneration.}, } @article {pmid38308282, year = {2024}, author = {Cai, R and Yang, J and Wu, L and Liu, Y and Wang, X and Zheng, Q and Li, L}, title = {Accelerating drug development for amyotrophic lateral sclerosis: construction and application of a disease course model using historical placebo group data.}, journal = {Orphanet journal of rare diseases}, volume = {19}, number = {1}, pages = {40}, pmid = {38308282}, issn = {1750-1172}, support = {82174229//the National Natural Science Funds of China/ ; 2022YFC3502000//China national key research and development program/ ; ZY [2021-2023]-0401//Shanghai 3-year Action Plan for Inheritance, Innovation, and Development of traditional Chinese Medicine/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/drug therapy ; Humans ; *Drug Development ; *Riluzole/therapeutic use ; Male ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is an irreversible degenerative disease. Placebo-controlled randomized trials are currently the main trial design to assess the clinical efficacy of drugs for ALS treatment. The aim of this study was to establish models to quantitatively describe the course of ALS, explore influencing factors, and provide the necessary information for ALS drug development.

METHODS: We conducted a comprehensive search of PubMed and the Cochrane Library Central Register for placebo-controlled trials that evaluated treatments for ALS. From these trials, we extracted the clinical and demographic characteristics of participants in the placebo group, as well as outcome data, which encompassed overall survival (OS) and Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) scores, at various time points.

RESULTS: In total, 47 studies involving 6118 participants were included. Disease duration and the proportion of patients receiving riluzole were identified as significant factors influencing OS in the placebo group. Specifically, the median OS was 35.5 months for a disease duration of 9 months, whereas it was 20.0 months for a disease duration of 36 months. Furthermore, for every 10% increase in the proportion of patients treated with riluzole (100 mg daily), there was an association with a median OS extension of approximately 0.4 months. The estimated time for the ALSFRS-R score in the placebo group to decrease to 50% of its maximum effect from baseline level was approximately 17.5 months, and the time to reach a plateau was about 40 months.

CONCLUSIONS: The established disease course model of the historical placebo group is valuable in the decision-making process for the clinical development of ALS drugs. It serves not only as an external control to evaluate the efficacy of the tested drug in single-arm trials but also as prior information that aids in accurately estimating the posterior distribution of the disease course in the placebo group during small-sample clinical trials.}, } @article {pmid38306019, year = {2024}, author = {Kasper, E and Temp, AGM and Köckritz, V and Meier, L and Machts, J and Vielhaber, S and Hermann, A and Prudlo, J}, title = {Verbal expressive language minimally affected in non-demented people living with amyotrophic lateral sclerosis.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {25}, number = {3-4}, pages = {308-316}, doi = {10.1080/21678421.2024.2307512}, pmid = {38306019}, issn = {2167-9223}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis ; Bayes Theorem ; Dysarthria/etiology ; Language ; *Language Disorders ; *Communication Disorders ; Neuropsychological Tests ; }, abstract = {Objective: Language dysfunction is one of the most common cognitive impairments in amyotrophic lateral sclerosis (ALS). Although discourse capacities are essential for daily functioning, verbal expressive language has not been widely investigated in ALS. The existing research available suggests that discourse impairments are prevalent. This study investigates verbal expressive language in people living with ALS (plwALS) in contrast to healthy controls (HC).Methods: 64 plwALS and 49 age, gender and education-matched healthy controls were ask to describe the Cookie Theft Picture Task. The recordings were analyzed for discourse productivity, discourse content, syntactic complexity, speech fluency and verb processing. We applied the Bayesian hypothesis-testing framework, incorporating the effects of dysarthria, cognitive impairment status (CIS), and premorbid crystalline verbal IQ.Results: Compared to HC, plwALS only showed a single impairment: speech dysfluency. Discourse productivity, discourse content, syntactic complexity and verb processing were not impaired. Cognition and dysarthria exceeded the influence of verbal IQ for total words spoken and content density. Cognition alone seemed to explain dysfluency. Body-agent verbs were produced at even higher rates than other verb types. For the remaining outcomes, verbal IQ was the most decisive factor.Conclusions: In contrast to existing research, our data demonstrates no discernible impairment in verbal expressive language in ALS. What our findings show to be decisive is accounting for the influence of dysarthria, cognitive impairment status, and verbal IQ as variables on spontaneous verbal expressive language. Minor impairments in verbal expressive language appear to be influenced to a greater degree by executive dysfunctioning and dysarthria than by language impairment.}, } @article {pmid38305586, year = {2024}, author = {Raghav, Y and Dilliott, AA and Petrozziello, T and Kim, SE and Berry, JD and Cudkowicz, ME and Vakili, K and , and Fraenkel, E and Farhan, SMK and Sadri-Vakili, G}, title = {Identification of gene fusions associated with amyotrophic lateral sclerosis.}, journal = {Muscle & nerve}, volume = {69}, number = {4}, pages = {477-489}, doi = {10.1002/mus.28043}, pmid = {38305586}, issn = {1097-4598}, support = {//ALS Finding a Cure/ ; //Active Against ALS/ ; //Answer ALS Foundation/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/pathology ; *Neurodegenerative Diseases ; Motor Neurons/pathology ; Gene Fusion ; }, abstract = {INTRODUCTION/AIMS: Genetics is an important risk factor for amyotrophic lateral sclerosis (ALS), a neurodegenerative disease affecting motor neurons. Recent findings demonstrate that in addition to specific genetic mutations, structural variants caused by genetic instability can also play a causative role in ALS. Genomic instability can lead to deletions, duplications, insertions, inversions, and translocations in the genome, and these changes can sometimes lead to fusion of distinct genes into a single transcript. Gene fusion events have been studied extensively in cancer; however, they have not been thoroughly investigated in ALS. The aim of this study was to determine whether gene fusions are present in ALS.

METHODS: Gene fusions were identified using STAR Fusion v1.10.0 software in bulk RNA-Seq data from human postmortem samples from publicly available data sets from Target ALS and the New York Genome Center ALS Consortium.

RESULTS: We report the presence of gene fusion events in several brain regions as well as in spinal cord samples in ALS. Although most gene fusions were intra-chromosomal events between neighboring genes and present in both ALS and control samples, there was a significantly greater number of unique gene fusions in ALS compared to controls. Lastly, we identified specific gene fusions with a significant burden in ALS, that were absent from both control samples and known cancer gene fusion databases.

DISCUSSION: Collectively, our findings reveal an enrichment of gene fusions in ALS and suggest that these events may be an additional genetic cause linked to ALS pathogenesis.}, } @article {pmid38304795, year = {2024}, author = {Matsuura, S and Tatebe, H and Higuchi, M and Tokuda, T}, title = {Validation of a newly developed immunoassay for TDP-43 in human plasma.}, journal = {Heliyon}, volume = {10}, number = {2}, pages = {e24672}, pmid = {38304795}, issn = {2405-8440}, abstract = {The level of TAR DNA-binding protein 43 (TDP-43) in human blood was reported to have potential for use as a specific fluid biomarker, which represents disease-specific pathologies, for TDP-43 proteinopathies, including amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD), which involves the aggregation and deposition of TDP-43 in the nervous system. However, at present, no reliable immunoassay can precisely quantify TDP-43 in human plasma and detect the difference in plasma TDP-43 levels between patients with ALS and controls. We recently developed a novel ultrasensitive immunoassay to quantify TDP-43 in human plasma, and in this study, we analytically validated this assay for application as a diagnostic biomarker for TDP-43 proteinopathies. The novel TDP-43 assay was assessed for the limit of detection, lower limit of quantification, intra- and interassay variation, linearity, parallelism, and analytical spike recoveries. Additionally, 17 pilot plasma samples obtained from patients with ALS and age-matched controls were analyzed using the assay. Our novel TDP-43 assay showed sufficient analytical performance to quantify TDP-43 in human plasma, with high sensitivity (LOD and LLOQ of 0.109 and 0.759 pg/mL, respectively) and high intra- and interassay precision (%CV) below 15 %. The experimental results for spike recovery, parallelism, and dilution linearity were also acceptable. In addition, despite a small sample size, significant differences in the plasma levels of TDP-43 were found between patients with ALS and controls (ALS, 66.63 ± 20.52 pg/mL; control, 42.70 ± 23.06 pg/mL, p = 0.0330). These results support that our novel TDP-43 assay is a reliable and innovative method for the quantification of TDP-43 in human plasma and can be a potential blood-based biomarker for the diagnosis of TDP-43 proteinopathies. Further large-scale studies are warranted to validate its usefulness.}, } @article {pmid38304328, year = {2023}, author = {Phillips, MCL and Johnston, SE and Simpson, P and Chang, DK and Mather, D and Dick, RJ}, title = {Time-restricted ketogenic diet in amyotrophic lateral sclerosis: a case study.}, journal = {Frontiers in neurology}, volume = {14}, number = {}, pages = {1329541}, pmid = {38304328}, issn = {1664-2295}, abstract = {Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disorder. The most devastating variant is bulbar-onset ALS, which portends a median survival of 24 months from the onset of symptoms. Abundant evidence indicates that neuron metabolism and mitochondrial function are impaired in ALS. Metabolic strategies, particularly fasting and ketogenic diet protocols, alter neuron metabolism and mitochondria function in a manner that may mitigate the symptoms of this disorder. We report the case of a 64-year-old man with a 21-month history of progressive, deteriorating bulbar-onset ALS, with an associated pseudobulbar affect, who implemented a time-restricted ketogenic diet (TRKD) for 18 months. During this time, he improved in ALS-related function (7% improvement from baseline), forced expiratory volume (17% improvement), forced vital capacity (13% improvement), depression (normalized), stress levels (normalized), and quality of life (19% improvement), particularly fatigue (23% improvement). His swallowing impairment and neurocognitive status remained stable. Declines were measured in physical function, maximal inspiratory pressure, and maximal expiratory pressure. Weight loss was attenuated and no significant adverse effects occurred. This case study represents the first documented occurrence of a patient with ALS managed with either a fasting or ketogenic diet protocol, co-administered as a TRKD. We measured improved or stabilized ALS-related function, forced expiratory volume, forced vital capacity, swallowing, neurocognitive status, mood, and quality of life. Measurable declines were restricted to physical function, maximal inspiratory pressure, and maximal expiratory pressure. Now over 45 months since symptom onset, our patient remains functionally independent and dedicated to his TRKD.}, } @article {pmid38304180, year = {2024}, author = {Kreiml, V and Sauter, A and Abu-Omar, K and Eickmann, S and Herrmann-Johns, A}, title = {"That's like therapy"-A qualitative study on socially disadvantaged women's views on the effects of a community-based participatory research project on their health and health behavior.}, journal = {Frontiers in public health}, volume = {12}, number = {}, pages = {1339556}, pmid = {38304180}, issn = {2296-2565}, mesh = {Humans ; Female ; *Community-Based Participatory Research ; *Health Behavior ; Health Promotion/methods ; Exercise ; Social Support ; }, abstract = {BACKGROUND: Regular physical activity has positive effects on both physical and mental health. Nevertheless, socially disadvantaged women are often insufficiently physically active. Through needs-based physical activity offers, community-based participatory research (CBPR) projects have the potential to reach these women and increase the effectiveness of physical activity interventions by supporting women's empowerment, health, and health behaviors. This study aimed to examine socially disadvantaged women's views on the effects of long-term participation in Bewegung als Investition in Gesundheit (BIG, i.e., movement as an investment in health), a long-standing German CBPR project, on their health and health behavior.

METHODS: Semi-structured qualitative interviews were conducted with 30 participating women at five BIG sites across Germany between April and August 2022. The interviews were recorded, transcribed verbatim, and analyzed using framework analysis.

RESULTS: Women reported that participation in BIG classes contributed to their physical, mental, and social health. For many women, the positive effects on their mental and social wellbeing were most important. In addition to increased fitness and improved physical endurance, many participating women were able to expand their social networks, thus receiving further social support, and improve their self-esteem, self-confidence, and self-efficacy. Furthermore, participation in BIG physical activity classes positively influenced the health awareness of many women helping them to improve their activity level and diet over time.

CONCLUSION: Our results suggest that CBPR projects, such as the BIG project, can increase physical activity among socially disadvantaged groups and contribute to their overall health and wellbeing. CBPR projects could thus be considered a key element of health promotion for this target group. Future interventional research is required to confirm and further explore the effects of CBPR interventions and to examine whether the effects can be replicated in other settings.}, } @article {pmid38302810, year = {2024}, author = {Teixeira, LCR and Mamede, I and Luizon, MR and Gomes, KB}, title = {Role of long non-coding RNAs in the pathophysiology of Alzheimer's disease and other dementias.}, journal = {Molecular biology reports}, volume = {51}, number = {1}, pages = {270}, pmid = {38302810}, issn = {1573-4978}, mesh = {Humans ; *Alzheimer Disease/genetics ; *RNA, Long Noncoding/genetics ; Amyloid beta-Peptides ; *Frontotemporal Dementia ; }, abstract = {Dementia is the term used to describe a group of cognitive disorders characterized by a decline in memory, thinking, and reasoning abilities that interfere with daily life activities. Examples of dementia include Alzheimer's Disease (AD), Frontotemporal dementia (FTD), Amyotrophic lateral sclerosis (ALS), Vascular dementia (VaD) and Progressive supranuclear palsy (PSP). AD is the most common form of dementia. The hallmark pathology of AD includes formation of β-amyloid (Aβ) oligomers and tau hyperphosphorylation in the brain, which induces neuroinflammation, oxidative stress, synaptic dysfunction, and neuronal apoptosis. Emerging studies have associated long non-coding RNAs (lncRNAs) with the pathogenesis and progression of the neurodegenerative diseases. LncRNAs are defined as RNAs longer than 200 nucleotides that lack the ability to encode functional proteins. LncRNAs play crucial roles in numerous biological functions for their ability to interact with different molecules, such as proteins and microRNAs, and subsequently regulate the expression of their target genes at transcriptional and post-transcriptional levels. In this narrative review, we report the function and mechanisms of action of lncRNAs found to be deregulated in different types of dementia, with the focus on AD. Finally, we discuss the emerging role of lncRNAs as biomarkers of dementias.}, } @article {pmid38302474, year = {2024}, author = {Fernández-Beltrán, LC and Ali, Z and Larrad-Sanz, A and Lopez-Carbonero, JI and Godoy-Corchuelo, JM and Jimenez-Coca, I and Garcia-Toledo, I and Bentley, L and Gomez-Pinedo, U and Matias-Guiu, JA and Gil-Moreno, MJ and Matias-Guiu, J and Corrochano, S}, title = {Leptin haploinsufficiency exerts sex-dependent partial protection in SOD1[G93A] mice by reducing inflammatory pathways in the adipose tissue.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {2671}, pmid = {38302474}, issn = {2045-2322}, support = {2018-T1/BMD-10731//Consejeria de Educacion, Ciencia y Universidades de la Comunidad de Madrid/ ; 2018-T1/BMD-10731//Consejeria de Educacion, Ciencia y Universidades de la Comunidad de Madrid/ ; INT20/00079//European Regional Development/ ; }, mesh = {Animals ; Female ; Humans ; Male ; Mice ; Adipose Tissue/metabolism ; *Amyotrophic Lateral Sclerosis/metabolism ; Disease Models, Animal ; Haploinsufficiency ; Leptin/metabolism ; Mice, Transgenic ; Spinal Cord/metabolism ; Superoxide Dismutase/metabolism ; Superoxide Dismutase-1/genetics/metabolism ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by significant metabolic disruptions, including weight loss and hypermetabolism in both patients and animal models. Leptin, an adipose-derived hormone, displays altered levels in ALS. Genetically reducing leptin levels (Lepob/+) to maintain body weight improved motor performance and extended survival in female SOD1G93A mice, although the exact molecular mechanisms behind these effects remain elusive. Here, we corroborated the sexual dimorphism in circulating leptin levels in ALS patients and in SOD1G93A mice. We reproduced a previous strategy to generate a genetically deficient leptin SOD1G93A mice (SOD1G93ALepob/+) and studied the transcriptomic profile in the subcutaneous adipose tissue and the spinal cord. We found that leptin deficiency reduced the inflammation pathways activated by the SOD1G93A mutation in the adipose tissue, but not in the spinal cord. These findings emphasize the importance of considering sex-specific approaches in metabolic therapies and highlight the role of leptin in the systemic modulation of ALS by regulating immune responses outside the central nervous system.}, } @article {pmid38302116, year = {2024}, author = {Ikeda, T and Yamazaki, K and Okumura, F and Kamura, T and Nakatsukasa, K}, title = {Role of the San1 ubiquitin ligase in the heat stress-induced degradation of nonnative Nup1 in the nuclear pore complex.}, journal = {Genetics}, volume = {226}, number = {4}, pages = {}, doi = {10.1093/genetics/iyae017}, pmid = {38302116}, issn = {1943-2631}, support = {//Toray Science Foundation/ ; //Toyoaki Scholarship Foundation/ ; 15K18503//JSPS KAKENHI/ ; //Institute for Fermentation, Osaka/ ; //Hori Science and Arts Foundation/ ; }, mesh = {Nuclear Pore/genetics/chemistry/metabolism ; Nuclear Pore Complex Proteins/genetics/metabolism ; *Proteasome Endopeptidase Complex/metabolism ; Saccharomyces cerevisiae/genetics/metabolism ; *Saccharomyces cerevisiae Proteins/genetics/metabolism ; Ubiquitin/analysis/genetics/metabolism ; Ubiquitin-Protein Ligases/genetics/metabolism ; }, abstract = {The nuclear pore complex (NPC) mediates the selective exchange of macromolecules between the nucleus and the cytoplasm. Neurodegenerative diseases such as amyotrophic lateral sclerosis are characterized by mislocalization of nucleoporins (Nups), transport receptors, and Ras-related nuclear proteins into nucleoplasmic or cytosolic aggregates, underscoring the importance of precise assembly of the NPC. The assembly state of large protein complexes is strictly monitored by the protein quality control system. The ubiquitin-proteasome system may eliminate aberrant, misfolded, and/or orphan components; however, the involvement of the ubiquitin-proteasome system in the degradation of nonnative Nups in the NPC remains unclear. Here, we show that in Saccharomyces cerevisiae, although Nup1 (the FG-Nup component of the central core of the NPC) was stable, C-terminally green fluorescent protein-tagged Nup1, which had been incorporated into the NPC, was degraded by the proteasome especially under heat stress conditions. The degradation was dependent on the San1 ubiquitin ligase and Cdc48/p97, as well as its cofactor Doa1. We also demonstrate that San1 weakly but certainly contributes to the degradation of nontagged endogenous Nup1 in cells defective in NPC biogenesis by the deletion of NUP120. In addition, the overexpression of SAN1 exacerbated the growth defect phenotype of nup120Δ cells, which may be caused by excess degradation of defective Nups due to the deletion of NUP120. These biochemical and genetic data suggest that San1 is involved in the degradation of nonnative Nups generated by genetic mutation or when NPC biogenesis is impaired.}, } @article {pmid38301895, year = {2024}, author = {Gotoh, S and Mori, K and Fujino, Y and Kawabe, Y and Yamashita, T and Omi, T and Nagata, K and Tagami, S and Nagai, Y and Ikeda, M}, title = {eIF5 stimulates the CUG initiation of RAN translation of poly-GA dipeptide repeat protein (DPR) in C9orf72 FTLD/ALS.}, journal = {The Journal of biological chemistry}, volume = {300}, number = {3}, pages = {105703}, pmid = {38301895}, issn = {1083-351X}, support = {P40 OD018537/OD/NIH HHS/United States ; }, mesh = {Animals ; *Amyotrophic Lateral Sclerosis/genetics/physiopathology ; *C9orf72 Protein/genetics ; Dipeptides/genetics ; *DNA Repeat Expansion/genetics ; Drosophila/genetics/metabolism ; *Eukaryotic Initiation Factor-5/genetics/metabolism ; *Frontotemporal Lobar Degeneration/genetics/physiopathology ; HeLa Cells ; Humans ; Disease Models, Animal ; }, abstract = {Tandem GGGGCC repeat expansion in C9orf72 is a genetic cause of frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). Transcribed repeats are translated into dipeptide repeat proteins via repeat-associated non-AUG (RAN) translation. However, the regulatory mechanism of RAN translation remains unclear. Here, we reveal a GTPase-activating protein, eukaryotic initiation factor 5 (eIF5), which allosterically facilitates the conversion of eIF2-bound GTP into GDP upon start codon recognition, as a novel modifier of C9orf72 RAN translation. Compared to global translation, eIF5, but not its inactive mutants, preferentially stimulates poly-GA RAN translation. RAN translation is increased during integrated stress response, but the stimulatory effect of eIF5 on poly-GA RAN translation was additive to the increase of RAN translation during integrated stress response, with no further increase in phosphorylated eIF2α. Moreover, an alteration of the CUG near cognate codon to CCG or AUG in the poly-GA reading frame abolished the stimulatory effects, indicating that eIF5 primarily acts through the CUG-dependent initiation. Lastly, in a Drosophila model of C9orf72 FTLD/ALS that expresses GGGGCC repeats in the eye, knockdown of endogenous eIF5 by two independent RNAi strains significantly reduced poly-GA expressions, confirming in vivo effect of eIF5 on poly-GA RAN translation. Together, eIF5 stimulates the CUG initiation of poly-GA RAN translation in cellular and Drosophila disease models of C9orf72 FTLD/ALS.}, } @article {pmid38301596, year = {2024}, author = {Wang, H and Liu, YT and Ren, YL and Guo, XY and Wang, Y}, title = {Association of peripheral immune activation with amyotrophic lateral sclerosis and Parkinson's disease: A systematic review and meta-analysis.}, journal = {Journal of neuroimmunology}, volume = {388}, number = {}, pages = {578290}, doi = {10.1016/j.jneuroim.2024.578290}, pmid = {38301596}, issn = {1872-8421}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/immunology ; Biomarkers ; *Neurodegenerative Diseases/immunology ; *Parkinson Disease/immunology ; }, abstract = {BACKGROUND: Recent studies have revealed the link between immune activation and neurodegenerative diseases.

METHODS: By employing meta-analysis, we estimated the standardized mean difference (SMD) and their corresponding 95% confidence intervals (CIs) between the groups.

RESULTS: According to the pre-set criteria, a total of 21 published articles including 2377 ALS patients and 1244 HCs, as well as 60 articles including 5111 PD patients and 4237 HCs, were identified. This study provided evidence of peripheral immune activation in the pathogenesis of ALS and PD.

CONCLUSION: Our results suggested monitoring changes in peripheral blood immune cell populations, particularly lymphocyte subsets, will benefit understanding the developments and exploring reliable and specific biomarkers of these two diseases.}, } @article {pmid38300375, year = {2024}, author = {Sarkar, S and Patranabis, S}, title = {Emerging Role of Extracellular Vesicles in Intercellular Communication in the Brain: Implications for Neurodegenerative Diseases and Therapeutics.}, journal = {Cell biochemistry and biophysics}, volume = {82}, number = {2}, pages = {379-398}, pmid = {38300375}, issn = {1559-0283}, mesh = {Humans ; *Extracellular Vesicles/metabolism ; *Neurodegenerative Diseases/metabolism/therapy/pathology ; *Cell Communication ; *Brain/metabolism/pathology ; Animals ; }, abstract = {Extracellular vesicles (EVs) are minute lipid-bilayer sacs discharged by cells, encompassing a diverse array of proteins, nucleic acids, and lipids. The identification of EVs as pivotal agents in intercellular communication has sparked compelling research pathways in the realms of cell biology and neurodegenerative diseases. Utilizing EVs for medicinal reasons has garnered interest due to the adaptability of EV-mediated communication. EVs can be classified based on their physical characteristics, biochemical composition, or cell of origin following purification. This review delves into the primary sub-types of EVs, providing an overview of the biogenesis of each type. Additionally, it explores the diverse environmental conditions triggering EV release and the originating cells, including stem cells and those from the Central Nervous System. Within the brain, EVs play a pivotal role as essential mediators of intercellular communication, significantly impacting synaptic plasticity, brain development, and the etiology of neurological diseases. Their potential diagnostic and therapeutic applications in various brain-related conditions are underscored, given their ability to carry specific cargo. Specially engineered EVs hold promise for treating diverse diseases, including neurodegenerative disorders. This study primarily emphasizes the diagnostic and potential therapeutic uses of EVs in neurological disorders such as Alzheimer's Disease, Huntington's Disease, Parkinson's Disease, Amyotrophic Lateral Sclerosis, and Prions disease. It also summarizes innovative techniques for detecting EVs in the brain, suggesting that EVs could serve as non-invasive biomarkers for early detection, disease monitoring, and prognosis in neurological disorders.}, } @article {pmid38299458, year = {2024}, author = {Villarruel, FD and Denofrio, MP and de León, TS and Erra-Balsells, R and Wolcan, E and García Einschlag, FS and Cabrerizo, FM}, title = {Exploring potooxidative degradation pathways of harmol and harmalol alkaloids in water: effects of pH, excitation sources and atmospheric conditions.}, journal = {Physical chemistry chemical physics : PCCP}, volume = {26}, number = {7}, pages = {6068-6079}, doi = {10.1039/d3cp05223k}, pmid = {38299458}, issn = {1463-9084}, mesh = {*Water ; *Alkaloids ; Indoles ; Hydrogen-Ion Concentration ; Harmaline/*analogs & derivatives ; Harmine/*analogs & derivatives ; }, abstract = {This work explores the photochemical degradation of cationic species of 7-hydroxy-1-methyl-2H-pyrido[3,4-b]indole or harmol (1C) and the corresponding partially hydrogenated derivative 7-hydroxy-1-methyl-3,4-dihydro-2H-pyrido[3,4-b]indole or harmalol (2C) in aqueous solution. UV-visible absorption and fluorescence emission spectroscopy coupled with multivariate data analysis (MCR-ALS and PARAFAC), HPLC and HRESI-MS techniques were used for both quantitative and qualitative analysis. The formation of hydrogen peroxide reactive oxygen species (ROS) was quantified, and the influence of pH, oxygen partial pressure and photoexcitation source on the photochemical degradation of both compounds was assessed. The potential implications on the biosynthesis of βCs and their biological role in living systems are discussed.}, } @article {pmid38297405, year = {2024}, author = {Larson, KC and Martens, LH and Marconi, M and Dejesus, C and Bruhn, S and Miller, TA and Tate, B and Levenson, JM}, title = {Preclinical translational platform of neuroinflammatory disease biology relevant to neurodegenerative disease.}, journal = {Journal of neuroinflammation}, volume = {21}, number = {1}, pages = {37}, pmid = {38297405}, issn = {1742-2094}, mesh = {Humans ; Mice ; Animals ; *Neurodegenerative Diseases/metabolism ; Neuroinflammatory Diseases ; Microglia/metabolism ; Inflammasomes/metabolism ; Biology ; }, abstract = {Neuroinflammation is a key driver of neurodegenerative disease, however the tools available to model this disease biology at the systems level are lacking. We describe a translational drug discovery platform based on organotypic culture of murine cortical brain slices that recapitulate disease-relevant neuroinflammatory biology. After an acute injury response, the brain slices assume a chronic neuroinflammatory state marked by transcriptomic profiles indicative of activation of microglia and astrocytes and loss of neuronal function. Microglia are necessary for manifestation of this neuroinflammation, as depletion of microglia prior to isolation of the brain slices prevents both activation of astrocytes and robust loss of synaptic function genes. The transcriptomic pattern of neuroinflammation in the mouse platform is present in published datasets derived from patients with amyotrophic lateral sclerosis, Huntington's disease, and frontotemporal dementia. Pharmacological utility of the platform was validated by demonstrating reversal of microglial activation and the overall transcriptomic signature with transforming growth factor-β. Additional anti-inflammatory targets were screened and inhibitors of glucocorticoid receptors, COX-2, dihydrofolate reductase, and NLRP3 inflammasome all failed to reverse the neuroinflammatory signature. Bioinformatics analysis of the neuroinflammatory signature identified protein tyrosine phosphatase non-receptor type 11 (PTPN11/SHP2) as a potential target. Three structurally distinct inhibitors of PTPN11 (RMC-4550, TN0155, IACS-13909) reversed the neuroinflammatory disease signature. Collectively, these results highlight the utility of this novel neuroinflammatory platform for facilitating identification and validation of targets for neuroinflammatory neurodegenerative disease drug discovery.}, } @article {pmid38297144, year = {2024}, author = {Sun, K and Ray, S and Gupta, N and Aldworth, Z and Stopfer, M}, title = {Olfactory system structure and function in newly hatched and adult locusts.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {2608}, pmid = {38297144}, issn = {2045-2322}, support = {Intramural Grant//National Institute of Child Health and Human Development/ ; }, mesh = {Animals ; *Grasshoppers ; Odorants ; Olfactory Pathways/physiology ; *Olfactory Receptor Neurons/physiology ; Interneurons ; Smell/physiology ; }, abstract = {An important question in neuroscience is how sensory systems change as animals grow and interact with the environment. Exploring sensory systems in animals as they develop can reveal how networks of neurons process information as the neurons themselves grow and the needs of the animal change. Here we compared the structure and function of peripheral parts of the olfactory pathway in newly hatched and adult locusts. We found that populations of olfactory sensory neurons (OSNs) in hatchlings and adults responded with similar tunings to a panel of odors. The morphologies of local neurons (LNs) and projection neurons (PNs) in the antennal lobes (ALs) were very similar in both age groups, though they were smaller in hatchlings, they were proportional to overall brain size. The odor evoked responses of LNs and PNs were also very similar in both age groups, characterized by complex patterns of activity including oscillatory synchronization. Notably, in hatchlings, spontaneous and odor-evoked firing rates of PNs were lower, and LFP oscillations were lower in frequency, than in the adult. Hatchlings have smaller antennae with fewer OSNs; removing antennal segments from adults also reduced LFP oscillation frequency. Thus, consistent with earlier computational models, the developmental increase in frequency is due to increasing intensity of input to the oscillation circuitry. Overall, our results show that locusts hatch with a fully formed olfactory system that structurally and functionally matches that of the adult, despite its small size and lack of prior experience with olfactory stimuli.}, } @article {pmid38296522, year = {2025}, author = {Kamiya, K and Hanashiro, S and Kano, O and Uchida, W and Kamagata, K and Aoki, S and Hori, M}, title = {Surface-based Analyses of Diffusional Kurtosis Imaging in Amyotrophic Lateral Sclerosis: Relationship with Onset Subtypes.}, journal = {Magnetic resonance in medical sciences : MRMS : an official journal of Japan Society of Magnetic Resonance in Medicine}, volume = {24}, number = {1}, pages = {122-132}, pmid = {38296522}, issn = {1880-2206}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnostic imaging/pathology ; Male ; Female ; Middle Aged ; Aged ; *Diffusion Magnetic Resonance Imaging/methods ; *Brain/diagnostic imaging/pathology ; Anisotropy ; Adult ; Image Processing, Computer-Assisted/methods ; Diffusion Tensor Imaging/methods ; }, abstract = {PURPOSE: Here, we aimed to characterize the cortical and subcortical microstructural alterations in the brains of patients with amyotrophic lateral sclerosis (ALS). In particular, we compared these features between bulbar-onset ALS (b-ALS) and limb-onset ALS (l-ALS).

METHODS: Diffusion MRI data (b = 0, 700, 2000 ms/mm[2], 1.7-mm isotropic voxel) from 28 patients with ALS (9 b-ALS and 19 l-ALS) and 17 healthy control subjects (HCs) were analyzed. Diffusional kurtosis imaging (DKI) metrics were sampled at the mid-cortical and subcortical surfaces. We used permutation testing with a nonparametric combination of mean diffusivity (MD), fractional anisotropy (FA), and mean kurtosis (MK) to assess intergroup differences over the cerebrum. We also carried out an atlas-based analysis focusing on Brodmann Area 4 and 6 (primary motor and premotor areas) and investigated the correlation between MRI metrics and clinical parameters.

RESULTS: At both the mid-cortical and subcortical surfaces, b-ALS was associated with significantly greater MD, smaller FA, and smaller MK in the motor and premotor areas than HC. In contrast, the patients with l-ALS showed relatively moderate differences relative to HCs. The ALS Functional Rating Scale-Revised bulbar subscore was significantly correlated with the diffusion metrics in Brodmann Area 4.

CONCLUSION: The distribution of abnormalities over the cerebral hemispheres and the more severe microstructural alteration in b-ALS compared to l-ALS were in good agreement with findings from postmortem histology. Our results suggest the feasibility of surface-based DKI analyses for exploring brain microstructural pathologies in ALS. The observed differences between b-ALS and l-ALS and their correlations with functional bulbar impairment support the clinical relevance of DKI measurement in the cortical and juxtacortical regions of patients with ALS.}, } @article {pmid38295187, year = {2024}, author = {Limone, F and Couto, A and Wang, JY and Zhang, Y and McCourt, B and Huang, C and Minkin, A and Jani, M and McNeer, S and Keaney, J and Gillet, G and Gonzalez, RL and Goodman, WA and Kadiu, I and Eggan, K and Burberry, A}, title = {Myeloid and lymphoid expression of C9orf72 regulates IL-17A signaling in mice.}, journal = {Science translational medicine}, volume = {16}, number = {732}, pages = {eadg7895}, pmid = {38295187}, issn = {1946-6242}, support = {R01 NS089742/NS/NINDS NIH HHS/United States ; R01 DK128143/DK/NIDDK NIH HHS/United States ; S10 OD021559/OD/NIH HHS/United States ; R01 AG085316/AG/NIA NIH HHS/United States ; T32 AI089474/AI/NIAID NIH HHS/United States ; R00 AG057808/AG/NIA NIH HHS/United States ; R35 NS097303/NS/NINDS NIH HHS/United States ; T32 AG071474/AG/NIA NIH HHS/United States ; K99 AG057808/AG/NIA NIH HHS/United States ; R03 AG080175/AG/NIA NIH HHS/United States ; }, mesh = {Animals ; Humans ; Mice ; *Amyotrophic Lateral Sclerosis/genetics/metabolism ; *C9orf72 Protein/genetics ; Endothelial Cells/metabolism ; *Frontotemporal Dementia/genetics/metabolism ; Interleukin-17 ; Neuroinflammatory Diseases ; }, abstract = {A mutation in C9ORF72 is the most common cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Patients with ALS or FTD often develop autoimmunity and inflammation that precedes or coincides with the onset of neurological symptoms, but the underlying mechanisms are poorly understood. Here, we knocked out murine C9orf72 in seven hematopoietic progenitor compartments by conditional mutagenesis and found that myeloid lineage C9orf72 prevents splenomegaly, loss of tolerance, and premature mortality. Furthermore, we demonstrated that C9orf72 plays a role in lymphoid cells to prevent interleukin-17A (IL-17A) production and neutrophilia. Mass cytometry identified early and sustained elevation of the costimulatory molecule CD80 expressed on C9orf72-deficient mouse macrophages, monocytes, and microglia. Enrichment of CD80 was similarly observed in human spinal cord microglia from patients with C9ORF72-mediated ALS compared with non-ALS controls. Single-cell RNA sequencing of murine spinal cord, brain cortex, and spleen demonstrated coordinated induction of gene modules related to antigen processing and presentation and antiviral immunity in C9orf72-deficient endothelial cells, microglia, and macrophages. Mechanistically, C9ORF72 repressed the trafficking of CD80 to the cell surface in response to Toll-like receptor agonists, interferon-γ, and IL-17A. Deletion of Il17a in C9orf72-deficient mice prevented CD80 enrichment in the spinal cord, reduced neutrophilia, and reduced gut T helper type 17 cells. Last, systemic delivery of an IL-17A neutralizing antibody augmented motor performance and suppressed neuroinflammation in C9orf72-deficient mice. Altogether, we show that C9orf72 orchestrates myeloid costimulatory potency and provide support for IL-17A as a therapeutic target for neuroinflammation associated with ALS or FTD.}, } @article {pmid38294285, year = {2024}, author = {Castro-Rodriguez, E and Azagra-Ledesma, R and Gómez-Batiste, X and Aguyé-Batista, A and Clemente-Azagra, C and Díaz-Herrera, MA}, title = {Complexity of needs in amyotrophic lateral sclerosis (ALS) patients using the ENP-E scale in the north-eastern region of Spain.}, journal = {Palliative & supportive care}, volume = {22}, number = {3}, pages = {460-469}, doi = {10.1017/S1478951523001773}, pmid = {38294285}, issn = {1478-9523}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/psychology/therapy/complications ; Male ; Spain ; Female ; Aged ; Middle Aged ; Longitudinal Studies ; Palliative Care/methods/statistics & numerical data/standards/psychology ; Needs Assessment/statistics & numerical data ; Aged, 80 and over ; Surveys and Questionnaires ; Terminal Care/methods/psychology/statistics & numerical data/standards ; }, abstract = {OBJECTIVES: This study aimed to explore the clinical characteristics of amyotrophic lateral sclerosis (ALS) patients in Spain's north-eastern region, their inclusion in chronic care programmes, and their psychosocial and spiritual needs (PSNs).

METHODS: A longitudinal descriptive study in adult patients with ALS. We analyzed clinical variables and participation in chronicity and PSNs assessment using the tool Psychosocial and Spiritual Needs Evaluation scale in end-of-life patients (ENP-E scale).

RESULTS: 81 patients (average age 65.6 ± 11.7) were studied. At the study's outset, 29.7% employed non-invasive ventilation (NIV), increasing to 51.9% by its conclusion. Initial percutaneous endoscopic gastrostomy (PEG) utilization was 14.8%, rising to 35.85%. Chronic care programme participation was as follows: home care (24.7% initially, 50.6% end), palliative care (16% initially, 40.7% end), case management (13.6% initially, 50.6% end), and advance care planning registration (6.2% initially, 35.8% end). At study start, 47.8% of patients (n = 46) showed moderate-to-severe complexity in PSNs assessment using the ENP-E scale, without showing differences in age, sex, and time of evolution; whereas, on the evolutionary analysis, it was 75% (n = 24). A higher evolutionary complexity was observed in males <60 and >70 years, with no PEG and evolution of ALS of <2 and ≥5 years, and not included in chronicity programmes. When assessing concerns, physical pain and family aspects stand out in all measurements. Forty-eight percent of patients at study start and 71% at end of study showed external signs of emotional distress.

SIGNIFICANCE OF RESULTS: Most ALS patients showed a high degree of complexity and were not integrated in chronicity programmes. A "care path" is proposed to integrate ALS patients in these programmes and systematically assess their needs.}, } @article {pmid38293807, year = {2024}, author = {Tang, D and Bao, H and Qi, S}, title = {The C9orf72-SMCR8 complex suppresses primary ciliogenesis as a RAB8A GAP.}, journal = {Autophagy}, volume = {20}, number = {5}, pages = {1205-1207}, pmid = {38293807}, issn = {1554-8635}, mesh = {*rab GTP-Binding Proteins/metabolism/genetics ; *Cilia/metabolism ; Humans ; *C9orf72 Protein/genetics/metabolism ; *Autophagy/genetics ; Animals ; Signal Transduction ; Hedgehog Proteins/metabolism ; HEK293 Cells ; GTPase-Activating Proteins/metabolism/genetics ; Protein Binding ; Mice ; Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology ; Carrier Proteins ; }, abstract = {Approximately half of the familial cases of amyotrophic lateral sclerosis (ALS) and frontal temporal dementia (FTD) are attributed to the abnormal GGGGCC repeat expansion within the first intron of C9orf72, potentializing C9orf72 and its product as the most promising target for ALS therapeutics. Nevertheless, the biological function of C9orf72 remains unclear. Previously, we reported that C9orf72 and its binding partner, SMCR8, form a GTPase-activating protein (GAP) complex, which is proposed to regulate membrane trafficking and autophagy. Hereby, we found that the C9orf72-SMCR8 complex negatively regulates primary ciliogenesis and hedgehog (HH) signaling. Furthermore, the biochemical analysis and cell biology experiments identified C9orf72 as the RAB8A binding subunit and SMCR8 as the GAP subunit within the complex. Further, we discussed the relationship among the C9orf72-SMCR8 complex, primary ciliogenesis, and autophagy.}, } @article {pmid38293619, year = {2023}, author = {Lu, B and Meng, R and Wang, Y and Xiong, W and Ma, Y and Gao, P and Ren, J and Zhang, L and Zhao, Z and Fan, G and Wen, Y and Yuan, X}, title = {Distinctive physiological and molecular responses of foxtail millet and maize to nicosulfuron.}, journal = {Frontiers in plant science}, volume = {14}, number = {}, pages = {1308584}, pmid = {38293619}, issn = {1664-462X}, abstract = {INTRODUCTION: Nicosulfuron is the leading acetolactate synthase inhibitor herbicide product, and widely used to control gramineous weeds. Here, we investigated the metabolic process of nicosulfuron into foxtail millet and maize, in order to clarify the mechanism of the difference in sensitivity of foxtail millet and maize to nicosulfuron from the perspective of physiological metabolism and provide a theoretical basis for the breeding of nicosulfuron-resistant foxtail millet varieties.

METHODS: We treated foxtail millet (Zhangzagu 10, Jingu 21) and maize (Nongda 108, Ditian 8) with various doses of nicosulfuron in both pot and field experiments. The malonaldehyde (MDA) content, target enzymes, detoxification enzymes, and antioxidant enzymes, as well as related gene expression levels in the leaf tissues of foxtail millet and maize were measured, and the yield was determined after maturity.

RESULTS: The results showed that the recommended dose of nicosulfuron caused Zhangzagu 10 and Jingu 21 to fail to harvest; the yield of the sensitive maize variety (Ditian 8) decreased by 37.09%, whereas that of the resistant maize variety (Nongda 108) did not decrease. Nicosulfuron stress increased the CYP450 enzyme activity, MDA content, and antioxidant enzyme activity of foxtail millet and maize, reduced the acetolactate synthase (ALS) activity and ALS gene expression of foxtail millet and Ditian 8, and reduced the glutathione S-transferase (GST) activity and GST gene expression of foxtail millet. In conclusion, target enzymes, detoxification enzymes, and antioxidant enzymes were involved in the detoxification metabolism of nicosulfuron in plants. ALS and GST are the main factors responsible for the metabolic differences among foxtail millet, sensitive maize varieties, and resistant maize varieties.

DISCUSSION: These findings offer valuable insights for exploring the target resistance (TSR) and non-target resistance (NTSR) mechanisms in foxtail millet under herbicide stress and provides theoretical basis for future research of develop foxtail millet germplasm with diverse herbicide resistance traits.}, } @article {pmid38292603, year = {2024}, author = {Weerawarna, PM and Schiefer, IT and Soares, P and Fox, S and Morimoto, RI and Melani, RD and Kelleher, NL and Luan, CH and Silverman, RB}, title = {Target Identification of a Class of Pyrazolone Protein Aggregation Inhibitor Therapeutics for Amyotrophic Lateral Sclerosis.}, journal = {ACS central science}, volume = {10}, number = {1}, pages = {87-103}, pmid = {38292603}, issn = {2374-7943}, support = {P41 GM108569/GM/NIGMS NIH HHS/United States ; R01 AG061708/AG/NIA NIH HHS/United States ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with no cure, and current treatment options are very limited. Previously, we performed a high-throughput screen to identify small molecules that inhibit protein aggregation caused by a mutation in the gene that encodes superoxide dismutase 1 (SOD1), which is responsible for about 25% of familial ALS. This resulted in three hit series of compounds that were optimized over several years to give three compounds that were highly active in a mutant SOD1 ALS model. Here we identify the target of two of the active compounds (6 and 7) with the use of photoaffinity labeling, chemical biology reporters, affinity purification, proteomic analysis, and fluorescent/cellular thermal shift assays. Evidence is provided to demonstrate that these two pyrazolone compounds directly interact with 14-3-3-E and 14-3-3-Q isoforms, which have chaperone activity and are known to interact with mutant SOD1[G93A] aggregates and become insoluble in the subcellular JUNQ compartment, leading to apoptosis. Because protein aggregation is the hallmark of all neurodegenerative diseases, knowledge of the target compounds that inhibit protein aggregation allows for the design of more effective molecules for the treatment of ALS and possibly other neurodegenerative diseases.}, } @article {pmid38292023, year = {2023}, author = {Ratano, P and Cocozza, G and Pinchera, C and Busdraghi, LM and Cantando, I and Martinello, K and Scioli, M and Rosito, M and Bezzi, P and Fucile, S and Wulff, H and Limatola, C and D'Alessandro, G}, title = {Reduction of inflammation and mitochondrial degeneration in mutant SOD1 mice through inhibition of voltage-gated potassium channel Kv1.3.}, journal = {Frontiers in molecular neuroscience}, volume = {16}, number = {}, pages = {1333745}, pmid = {38292023}, issn = {1662-5099}, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with no effective therapy, causing progressive loss of motor neurons in the spinal cord, brainstem, and motor cortex. Regardless of its genetic or sporadic origin, there is currently no cure for ALS or therapy that can reverse or control its progression. In the present study, taking advantage of a human superoxide dismutase-1 mutant (hSOD1-G93A) mouse that recapitulates key pathological features of human ALS, we investigated the possible role of voltage-gated potassium channel Kv1.3 in disease progression. We found that chronic administration of the brain-penetrant Kv1.3 inhibitor, PAP-1 (40 mg/Kg), in early symptomatic mice (i) improves motor deficits and prolongs survival of diseased mice (ii) reduces astrocyte reactivity, microglial Kv1.3 expression, and serum pro-inflammatory soluble factors (iii) improves structural mitochondrial deficits in motor neuron mitochondria (iv) restores mitochondrial respiratory dysfunction. Taken together, these findings underscore the potential significance of Kv1.3 activity as a contributing factor to the metabolic disturbances observed in ALS. Consequently, targeting Kv1.3 presents a promising avenue for modulating disease progression, shedding new light on potential therapeutic strategies for ALS.}, } @article {pmid38291418, year = {2024}, author = {Cai, Y and Peng, Z and He, Q and Sun, P}, title = {Behavioral variant frontotemporal dementia associated with GRN and ErbB4 gene mutations: a case report and literature review.}, journal = {BMC medical genomics}, volume = {17}, number = {1}, pages = {43}, pmid = {38291418}, issn = {1755-8794}, mesh = {Male ; Humans ; Middle Aged ; *Frontotemporal Dementia/genetics ; *Amyotrophic Lateral Sclerosis/genetics ; Positron Emission Tomography Computed Tomography ; Progranulins/genetics ; Mutation ; }, abstract = {OBJECTIVE: To report the clinical manifestation and genetic characteristics of a patient having frontotemporal dementia (FTD) with abnormal behavior and unstable walking.

METHODS: The clinical and imaging features of a patient who was eventually diagnosed with FTD were analyzed. The patient's neuropsychological, PET-CT, electromyography, and genetic data were collected. Furthermore, the patient's blood samples were examined for FTD-related genes.

RESULTS: The patient was a 52-year-old man with hidden onset. The symptoms progressed gradually, presenting with abnormal behaviors, including repeated shopping, taking away other people's things, constantly eating snacks, and frequently calling friends at night. The patient also exhibited executive dysfunction, such as the inability to cook and multiple driving problems, e.g., constantly deviates from his lane while driving. In addition, the patient showed personality changes such as irritability, indifference, and withdrawal, as well as motor symptoms, including unstable walking and frequent falls when walking. Brain magnetic resonance imaging revealed hippocampal sclerosis along with widening and deepening of the bilateral temporal lobe sulcus. Brain metabolic imaging via PET-CT demonstrated decreased metabolism in the bilateral prefrontal lobe, with the abnormal energy metabolism indicating FTD. Lastly, blood sample analysis detected mutations in the amyotrophic lateral sclerosis (ALS)-related GRN gene c.1352C > T (p.P451L) and ErbB4 gene c.256 T > C (p.Y86H).

CONCLUSION: This is the first case of heterozygous mutations in the GRN and ErbB4 genes in FTD alone. The GRN and ErbB4 genes are likely to be important in the pathogenesis of FTD, expanding the common genetic profile of ALS and FTD.}, } @article {pmid38290651, year = {2024}, author = {Lõhelaid, H and Saarma, M and Airavaara, M}, title = {CDNF and ER stress: Pharmacology and therapeutic possibilities.}, journal = {Pharmacology & therapeutics}, volume = {254}, number = {}, pages = {108594}, doi = {10.1016/j.pharmthera.2024.108594}, pmid = {38290651}, issn = {1879-016X}, mesh = {Animals ; Humans ; *Parkinson Disease/drug therapy ; Nerve Growth Factors/therapeutic use/metabolism ; Recombinant Proteins/therapeutic use ; }, abstract = {Cerebral dopamine neurotrophic factor (CDNF) is an endogenous protein in humans and other vertebrates, and it has been shown to have protective and restorative effects on cells in various disease models. Although it is named as a neurotrophic factor, its actions are drastically different from classical neurotrophic factors such as neurotrophins or the glial cell line-derived neurotrophic family of proteins. Like all secreted proteins, CDNF has a signal sequence at the N-terminus, but unlike common growth factors it has a KDEL-receptor retrieval sequence at the C-terminus. Thus, CDNF is mainly located in the ER. In response to adverse effects, such as ER stress, the expression of CDNF is upregulated and can alleviate ER stress. Also different from other neurotrophic factors, CDNF reduces protein aggregation and inflammation in disease models. Although it is an ER luminal protein, it can surprisingly directly interact with alpha-synuclein, a protein involved in the pathogenesis of synucleinopathies e.g., Parkinson's disease. Pleiotropic CDNF has therapeutic potential and has been tested as a recombinant human protein and gene therapy. The neuroprotective and neurorestorative effects have been described in a number of preclinical studies of Parkinson's disease, stroke and amyotrophic lateral sclerosis. Currently, it was successfully evaluated for safety in a phase 1/2 clinical trial for Parkinson's disease. Collectively, based on recent findings on the mode of action and therapeutic potential of CDNF, its use as a drug could be expanded to other ER stress-related diseases.}, } @article {pmid38290377, year = {2024}, author = {Takeda, T and Koreki, A and Kokubun, S and Saito, Y and Ishikawa, A and Isose, S and Ito, K and Arai, K and Kitagawa, K and Kuwabara, S and Honda, K}, title = {Deep vein thrombosis and its risk factors in neurodegenerative diseases: A markedly higher incidence in Parkinson's disease.}, journal = {Journal of the neurological sciences}, volume = {457}, number = {}, pages = {122896}, doi = {10.1016/j.jns.2024.122896}, pmid = {38290377}, issn = {1878-5883}, mesh = {Humans ; Female ; *Parkinson Disease/complications/diagnostic imaging/epidemiology ; *Amyotrophic Lateral Sclerosis ; Incidence ; *Supranuclear Palsy, Progressive ; *Multiple System Atrophy ; Risk Factors ; *Venous Thrombosis/diagnostic imaging/epidemiology ; }, abstract = {BACKGROUND: Information on the incidence and risk factors of deep vein thrombosis (DVT) in neurodegenerative diseases is limited. We aimed to determine the incidence of DVT among neurodegenerative disorders (amyotrophic lateral sclerosis [ALS], Parkinson's disease [PD], multiple system atrophy [MSA], and progressive supranuclear palsy [PSP]-corticobasal syndrome [CBS]) and the risk factors for the development of DVT.

METHODS: Overall, 229 hospitalized patients with neurodegenerative diseases (65 patients with ALS, 61 with PD, 53 with MSA, and 50 with PSP-CBS) were included in this study. D-dimer value and ultrasonography of the leg vein were assessed to determine the presence or absence of leg DVT. We compared the DVT incidence among each disease group. To identify the risk factors for DVT, a multivariate analysis was performed.

RESULTS: Of 229 patients, 34 had leg DVT; the incidence was significantly higher in patients with PD (38%) than in those with ALS (2%), MSA (5%), or PSP-CBS (4%). Patients with DVT were older, had a smaller waist circumference, had a longer disease duration, and had a high blood pressure (BP) variability. Multivariate analysis revealed that a PD diagnosis and female sex, with a high BP variability were predictive of leg DVT.

CONCLUSIONS: Among the neurodegenerative diseases, the DVT incidence was markedly higher in PD than in ALS, MSA, and PSP-CBS. Several risk factors have been identified in patients with leg DVT. Recognition of these risk factors will improve patient care and guide the appropriate use of anticoagulants.}, } @article {pmid38290242, year = {2024}, author = {Shadish, JA and Lee, JC}, title = {Genetically encoded lysine photocage for spatiotemporal control of TDP-43 nuclear import.}, journal = {Biophysical chemistry}, volume = {307}, number = {}, pages = {107191}, pmid = {38290242}, issn = {1873-4200}, support = {ZIA HL001055/ImNIH/Intramural NIH HHS/United States ; }, mesh = {Humans ; Active Transport, Cell Nucleus ; *Amyotrophic Lateral Sclerosis/genetics ; DNA-Binding Proteins/chemistry ; HEK293 Cells ; *Lysine/metabolism ; }, abstract = {Intracellular aggregation of transactive response DNA binding protein of 43 kDa (TDP-43) is a hallmark of neurodegenerative diseases such as amyotrophic lateral sclerosis. While primarily a nuclear protein, TDP-43 translocates to the cytosol during cellular stress. Consequences of cytosolic accumulation of TDP-43 is difficult to evaluate in the absence of exogenous toxins. Here, we demonstrate spatiotemporal control over the nuclear import of TDP-43 by installing a photocage (ortho-nitrobenzyl ester) on a single lysine residue (K84) through amber codon suppression in HEK293T cells. Translocation of this cytosolic construct is photo-triggerable in a dose-dependent manner with 355 nm light. Interestingly, both fluid- and solid-like puncta were found based on fluorescence recovery after photobleaching experiments, similar to what is expected of stress granules and intracellular aggregates, respectively. This optogenetic method is advantageous as it is minimally perturbative and broadly applicable to other studies of protein translocation between cellular compartments.}, } @article {pmid38289969, year = {2024}, author = {Hossain, MA and Sarin, R and Donnelly, DP and Miller, BC and Weiss, A and McAlary, L and Antonyuk, SV and Salisbury, JP and Amin, J and Conway, JB and Watson, SS and Winters, JN and Xu, Y and Alam, N and Brahme, RR and Shahbazian, H and Sivasankar, D and Padmakumar, S and Sattarova, A and Ponmudiyan, AC and Gawde, T and Verrill, DE and Yang, W and Kannapadi, S and Plant, LD and Auclair, JR and Makowski, L and Petsko, GA and Ringe, D and Agar, NYR and Greenblatt, DJ and Ondrechen, MJ and Chen, Y and Yerbury, JJ and Manetsch, R and Hasnain, SS and Brown, RH and Agar, JN}, title = {Evaluating protein cross-linking as a therapeutic strategy to stabilize SOD1 variants in a mouse model of familial ALS.}, journal = {PLoS biology}, volume = {22}, number = {1}, pages = {e3002462}, pmid = {38289969}, issn = {1545-7885}, support = {P30 GM124166/GM/NIGMS NIH HHS/United States ; R01 NS065263/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Mice ; *Amyotrophic Lateral Sclerosis/drug therapy/genetics/metabolism ; Cysteine/genetics ; Mutation ; Superoxide Dismutase/genetics/chemistry/metabolism ; Superoxide Dismutase-1/genetics ; }, abstract = {Mutations in the gene encoding Cu-Zn superoxide dismutase 1 (SOD1) cause a subset of familial amyotrophic lateral sclerosis (fALS) cases. A shared effect of these mutations is that SOD1, which is normally a stable dimer, dissociates into toxic monomers that seed toxic aggregates. Considerable research effort has been devoted to developing compounds that stabilize the dimer of fALS SOD1 variants, but unfortunately, this has not yet resulted in a treatment. We hypothesized that cyclic thiosulfinate cross-linkers, which selectively target a rare, 2 cysteine-containing motif, can stabilize fALS-causing SOD1 variants in vivo. We created a library of chemically diverse cyclic thiosulfinates and determined structure-cross-linking-activity relationships. A pre-lead compound, "S-XL6," was selected based upon its cross-linking rate and drug-like properties. Co-crystallographic structure clearly establishes the binding of S-XL6 at Cys 111 bridging the monomers and stabilizing the SOD1 dimer. Biophysical studies reveal that the degree of stabilization afforded by S-XL6 (up to 24°C) is unprecedented for fALS, and to our knowledge, for any protein target of any kinetic stabilizer. Gene silencing and protein degrading therapeutic approaches require careful dose titration to balance the benefit of diminished fALS SOD1 expression with the toxic loss-of-enzymatic function. We show that S-XL6 does not share this liability because it rescues the activity of fALS SOD1 variants. No pharmacological agent has been proven to bind to SOD1 in vivo. Here, using a fALS mouse model, we demonstrate oral bioavailability; rapid engagement of SOD1G93A by S-XL6 that increases SOD1G93A's in vivo half-life; and that S-XL6 crosses the blood-brain barrier. S-XL6 demonstrated a degree of selectivity by avoiding off-target binding to plasma proteins. Taken together, our results indicate that cyclic thiosulfinate-mediated SOD1 stabilization should receive further attention as a potential therapeutic approach for fALS.}, } @article {pmid38289193, year = {2024}, author = {Nolan, M and Scott, C and Hof, PR and Ansorge, O}, title = {Betz cells of the primary motor cortex.}, journal = {The Journal of comparative neurology}, volume = {532}, number = {1}, pages = {e25567}, pmid = {38289193}, issn = {1096-9861}, support = {ANSORGE/OCT14/877-792/MNDA_/Motor Neurone Disease Association/United Kingdom ; MR/L022656/1/MRC_/Medical Research Council/United Kingdom ; 14/877-792/MNDA_/Motor Neurone Disease Association/United Kingdom ; }, mesh = {Adult ; Humans ; Animals ; *Motor Cortex ; *Amyotrophic Lateral Sclerosis ; Pyramidal Cells ; Motor Neurons ; Primates ; Mammals ; }, abstract = {Betz cells, named in honor of Volodymyr Betz (1834-1894), who described them as "giant pyramids" in the primary motor cortex of primates and other mammalian species, are layer V extratelencephalic projection (ETP) neurons that directly innervate α-motoneurons of the brainstem and spinal cord. Despite their large volume and circumferential dendritic architecture, to date, no single molecular criterion has been established that unequivocally distinguishes adult Betz cells from other layer V ETP neurons. In primates, transcriptional signatures suggest the presence of at least two ETP neuron clusters that contain mature Betz cells; these are characterized by an abundance of axon guidance and oxidative phosphorylation transcripts. How neurodevelopmental programs drive the distinct positional and morphological features of Betz cells in humans remains unknown. Betz cells display a distinct biphasic firing pattern involving early cessation of firing followed by delayed sustained acceleration in spike frequency and magnitude. Few cell type-specific transcripts and electrophysiological characteristics are conserved between rodent layer V ETP neurons of the motor cortex and primate Betz cells. This has implications for the modeling of disorders that affect the motor cortex in humans, such as amyotrophic lateral sclerosis (ALS). Perhaps vulnerability to ALS is linked to the evolution of neural networks for fine motor control reflected in the distinct morphomolecular architecture of the human motor cortex, including Betz cells. Here, we discuss histological, molecular, and functional data concerning the position of Betz cells in the emerging taxonomy of neurons across diverse species and their role in neurological disorders.}, } @article {pmid38288970, year = {2024}, author = {Lini, RS and Scanferla, DTP and de Oliveira, NG and Aguera, RG and Santos, TDS and Teixeira, JJV and Kaneshima, AMS and Mossini, SAG}, title = {Fungicides as a risk factor for the development of neurological diseases and disorders in humans: a systematic review.}, journal = {Critical reviews in toxicology}, volume = {54}, number = {1}, pages = {35-54}, doi = {10.1080/10408444.2024.2303481}, pmid = {38288970}, issn = {1547-6898}, mesh = {Humans ; *Fungicides, Industrial/toxicity ; *Nervous System Diseases/chemically induced ; Risk Factors ; Brazil ; }, abstract = {Although studies show that pesticides, especially insecticides, may be toxic to humans, publications on the neurological effects of fungicides are scarce. As fungicides are used widely in Brazil, it is necessary to gather evidence to support actions aimed at safely using of these chemicals. We investigated through a systematic review of publications on the use of fungicides and consequences of exposure related to nervous system diseases or neurological disorders in humans. The protocol review was registered on PROSPERO and followed the guidelines of the PRISMA-Statement. As far as it is known, there is no apparent systematic review in the literature on this topic. The search was comprised of the following databases: PubMed; Web of Science; Scopus and EMBASE, using groups of Mesh terms and strategies specific to each database. Thirteen articles were selected for this review. Regarding the substances analyzed in the studies, some reported the use of fungicides in general, without separating them by type, while others summarized the categories of all pesticides by their function (insecticides, herbicides, fungicides, etc.) or chemical class (dithiocarbamate, dicarboximide, inorganic, etc.). However, most of the articles referred to fungicides that contain the metal manganese (Mn) in their composition. As for neurological disorders, articles addressed Parkinson's disease (PD), neurodevelopmental outcomes, extrapyramidal syndrome resembling PD, cognitive disorders, depression, neural tube defects, motor neurone disease, and amyotrophic lateral sclerosis. Most investigations pointed to exposure to fungicides, mainly maneb and mancozeb, leading to the development of at least one neurological disease, which suggests the need for further multicentric clinical trials and prospective studies for greater clarity of the research problem.}, } @article {pmid38288843, year = {2024}, author = {Fatima, J and Siddique, YH}, title = {Application of Nanocomposites and Nanoparticles in Treating Neurodegenerative Disorders.}, journal = {CNS & neurological disorders drug targets}, volume = {23}, number = {10}, pages = {1217-1233}, pmid = {38288843}, issn = {1996-3181}, support = {211610179057//University Grants Commission/ ; }, mesh = {Humans ; *Neurodegenerative Diseases/drug therapy ; *Nanoparticles/therapeutic use ; *Nanocomposites/therapeutic use ; Animals ; Drug Delivery Systems/methods ; Blood-Brain Barrier/drug effects/metabolism ; Neuroprotective Agents/therapeutic use ; }, abstract = {Neurodegenerative diseases represent a formidable global health challenge, affecting millions and imposing substantial burdens on healthcare systems worldwide. Conditions, like Alzheimer's, Parkinson's, and Huntington's diseases, among others, share common characteristics, such as neuronal loss, misfolded protein aggregation, and nervous system dysfunction. One of the major obstacles in treating these diseases is the presence of the blood-brain barrier, limiting the delivery of therapeutic agents to the central nervous system. Nanotechnology offers promising solutions to overcome these challenges. In Alzheimer's disease, NPs loaded with various compounds have shown remarkable promise in preventing amyloid-beta (Aβ) aggregation and reducing neurotoxicity. Parkinson's disease benefits from improved dopamine delivery and neuroprotection. Huntington's disease poses its own set of challenges, but nanotechnology continues to offer innovative solutions. The promising developments in nanoparticle-based interventions for neurodegenerative diseases, like amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS), have offered new avenues for effective treatment. Nanotechnology represents a promising frontier in biomedical research, offering tailored solutions to the complex challenges posed by neurodegenerative diseases. While much progress has been made, ongoing research is essential to optimize nanomaterial designs, improve targeting, and ensure biocompatibility and safety. Nanomaterials possess unique properties that make them excellent candidates for targeted drug delivery and neuroprotection. They can effectively bypass the blood-brain barrier, opening doors to precise drug delivery strategies. This review explores the extensive research on nanoparticles (NPs) and nanocomposites in diagnosing and treating neurodegenerative disorders. These nanomaterials exhibit exceptional abilities to target neurodegenerative processes and halt disease progression.}, } @article {pmid38288290, year = {2023}, author = {Aussenac, R and Monnet, JM and Klopčič, M and Hawryło, P and Socha, J and Mahnken, M and Gutsch, M and Cordonnier, T and Vallet, P}, title = {Diameter, height and species of 42 million trees in three European landscapes generated from field data and airborne laser scanning data.}, journal = {Open research Europe}, volume = {3}, number = {}, pages = {32}, pmid = {38288290}, issn = {2732-5121}, abstract = {Ecology and forestry sciences are using an increasing amount of data to address a wide variety of technical and research questions at the local, continental and global scales. However, one type of data remains rare: fine-grain descriptions of large landscapes. Yet, this type of data could help address the scaling issues in ecology and could prove useful for testing forest management strategies and accurately predicting the dynamics of ecosystem services. Here we present three datasets describing three large European landscapes in France, Poland and Slovenia down to the tree level. Tree diameter, height and species data were generated combining field data, vegetation maps and airborne laser scanning (ALS) data following an area-based approach. Together, these landscapes cover more than 100 000 ha and consist of more than 42 million trees of 51 different species. Alongside the data, we provide here a simple method to produce high-resolution descriptions of large landscapes using increasingly available data: inventory and ALS data. We carried out an in-depth evaluation of our workflow including, among other analyses, a leave-one-out cross validation. Overall, the landscapes we generated are in good agreement with the landscapes they aim to reproduce. In the most favourable conditions, the root mean square error (RMSE) of stand basal area (BA) and mean quadratic diameter (Dg) predictions were respectively 5.4 m [2].ha [-1] and 3.9 cm, and the generated main species corresponded to the observed main species in 76.2% of cases.}, } @article {pmid38287907, year = {2024}, author = {Pan, MT and Zhang, H and Li, XJ and Guo, XY}, title = {Genetically modified non-human primate models for research on neurodegenerative diseases.}, journal = {Zoological research}, volume = {45}, number = {2}, pages = {263-274}, pmid = {38287907}, issn = {2095-8137}, mesh = {Humans ; Animals ; Chlorocebus aethiops ; *Neurodegenerative Diseases/genetics/therapy/veterinary ; Animals, Genetically Modified ; Disease Models, Animal ; *Parkinson Disease/pathology/veterinary ; Macaca mulatta ; }, abstract = {Neurodegenerative diseases (NDs) are a group of debilitating neurological disorders that primarily affect elderly populations and include Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS). Currently, there are no therapies available that can delay, stop, or reverse the pathological progression of NDs in clinical settings. As the population ages, NDs are imposing a huge burden on public health systems and affected families. Animal models are important tools for preclinical investigations to understand disease pathogenesis and test potential treatments. While numerous rodent models of NDs have been developed to enhance our understanding of disease mechanisms, the limited success of translating findings from animal models to clinical practice suggests that there is still a need to bridge this translation gap. Old World non-human primates (NHPs), such as rhesus, cynomolgus, and vervet monkeys, are phylogenetically, physiologically, biochemically, and behaviorally most relevant to humans. This is particularly evident in the similarity of the structure and function of their central nervous systems, rendering such species uniquely valuable for neuroscience research. Recently, the development of several genetically modified NHP models of NDs has successfully recapitulated key pathologies and revealed novel mechanisms. This review focuses on the efficacy of NHPs in modeling NDs and the novel pathological insights gained, as well as the challenges associated with the generation of such models and the complexities involved in their subsequent analysis.}, } @article {pmid38287331, year = {2024}, author = {Oh, J and An, J and Park, K and Park, Y}, title = {Psychosocial interventions for people with amyotrophic lateral sclerosis and motor neuron disease and their caregivers: a scoping review.}, journal = {BMC nursing}, volume = {23}, number = {1}, pages = {75}, pmid = {38287331}, issn = {1472-6955}, support = {2022R1F1A1064038//National Research Foundation of Korea grant funded by the Korea government/ ; }, abstract = {BACKGROUND: As amyotrophic lateral sclerosis/motor neuron disease (ALS/MND) is a fatal progressive neurodegenerative disorder, patients experience severe impairments, with patients and family caregivers facing emotional distress and exhaustion. Several psychosocial interventions are aimed at providing tailored support for ALS/MND patients and caregivers. The aim of this study was to conduct a scoping review and present a comprehensive overview of psychosocial interventions designed for individuals and families affected by ALS/MND, while also pinpointing research gaps.

METHODS: This scoping review utilized Arksey and O'Malley's methodological framework to investigate psychosocial interventions designed for individuals with ALS/MND and their families. The study adhered to the PRISMA-ScR checklist for reporting.

RESULTS: A total of 27 articles describing 25 interventions met the inclusion criteria. The predominant interventions observed in the research encompassed education-related strategies, closely followed by behavior therapy, counseling, social support interventions, and psychotherapy interventions. Across the majority of the studies, findings indicated promising feasibility and acceptability of these interventions. Notably, a significant proportion of quantitative investigations yielded one or more statistically significant effects, while qualitative studies consistently reported favorable outcomes, including enhancements in well-being and heightened awareness of individual circumstances.

CONCLUSIONS: Given the progressive and debilitating nature of this condition, coupled with the absence of a cure, the adoption of a psychosocial approach can prove beneficial for both ALS/MND patients and their families. However, high-quality RCTs with a large sample size are recommended to examine and confirm the effectiveness.}, } @article {pmid38287112, year = {2024}, author = {Wang, J and Wang, Y and Zhang, Q and Li, SZ and He, MG and Wang, N and Zhang, Y}, title = {Quantitative analysis of dynamic iris changes in primary angle-closure disease with long axial lengths: the Handan Eye Study.}, journal = {Eye (London, England)}, volume = {38}, number = {7}, pages = {1362-1367}, pmid = {38287112}, issn = {1476-5454}, mesh = {Humans ; *Glaucoma, Angle-Closure/physiopathology/diagnosis ; Cross-Sectional Studies ; Female ; Male ; *Tomography, Optical Coherence/methods ; Middle Aged ; *Axial Length, Eye/pathology/diagnostic imaging ; *Iris/pathology/diagnostic imaging ; Aged ; Adult ; Intraocular Pressure/physiology ; Gonioscopy ; Anterior Chamber/pathology/diagnostic imaging ; }, abstract = {OBJECTIVE: To investigate dynamic iris changes in patients with primary angle-closure disease (PACD) with long axial length (AL) compared to those with short and medium AL.

METHODS: This observational cross-sectional study enrolled participants aged 35 years or older from the Handan Eye Study follow-up examination who were diagnosed with PACD and underwent Visante anterior segment optical coherence tomography (ASOCT) imaging under light and dark conditions. The right eye of each participant was included in the analysis. AL was categorized as short (<22.0 mm), medium (≥22.0 to ≤23.5 mm), or long (>23.5 mm). Anterior segment parameters, including iris dynamic changes, were compared among the three groups with different ALs.

RESULTS: Data from 448 patients with PACD were analyzed. We found that 10.9% of included eyes had a long AL with a flatter cornea; larger central anterior chamber depth, angle opening distance, anterior chamber width, anterior chamber area, and volume; and smaller lens thickness and lens vault (LV) (P < 0.05) than those with short AL. No significant difference existed between the three groups in iris thickness, iris cross-sectional area (IA), iris curvature, or pupil diameter (PD) change between light and dark (P > 0.05). The significant associated factors for IA changes were area recess area (ARA) in the dark, LV in the dark, and PD change from light to dark (P < 0.05).

CONCLUSIONS: Dynamic and static iris parameters were consistent across patients with PACD with short, medium, or long AL and may contribute to the pathogenesis of angle closure in atypical PACD.}, } @article {pmid38286832, year = {2024}, author = {Lu, J and He, AX and Jin, ZY and Zhang, M and Li, ZX and Zhou, F and Ma, L and Jin, HM and Wang, JY and Shen, X}, title = {Desloratadine alleviates ALS-like pathology in hSOD1[G93A] mice via targeting 5HTR2A on activated spinal astrocytes.}, journal = {Acta pharmacologica Sinica}, volume = {45}, number = {5}, pages = {926-944}, pmid = {38286832}, issn = {1745-7254}, mesh = {Animals ; Humans ; Male ; Mice ; *Amyotrophic Lateral Sclerosis/drug therapy/metabolism/pathology ; *Astrocytes/drug effects/metabolism/pathology ; Disease Models, Animal ; *Loratadine/analogs & derivatives/pharmacology/therapeutic use/analogs & derivatives ; Mice, Inbred C57BL ; *Mice, Transgenic ; Receptor, Serotonin, 5-HT2A/genetics/metabolism ; Serotonin 5-HT2 Receptor Antagonists/pharmacology/therapeutic use ; *Spinal Cord/drug effects/pathology/metabolism ; *Superoxide Dismutase-1/genetics/metabolism ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with progressive loss of motor neurons in the spinal cord, cerebral cortex and brain stem. ALS is characterized by gradual muscle atrophy and dyskinesia. The limited knowledge on the pathology of ALS has impeded the development of therapeutics for the disease. Previous studies have shown that autophagy and astrocyte-mediated neuroinflammation are involved in the pathogenesis of ALS, while 5HTR2A participates in the early stage of astrocyte activation, and 5HTR2A antagonism may suppress astrocyte activation. In this study, we evaluated the therapeutic effects of desloratadine (DLT), a selective 5HTR2A antagonist, in human SOD1[G93A] (hSOD1[G93A]) ALS model mice, and elucidated the underlying mechanisms. HSOD1[G93A] mice were administered DLT (20 mg·kg[-1]·d[-1], i.g.) from the age of 8 weeks for 10 weeks or until death. ALS onset time and lifespan were determined using rotarod and righting reflex tests, respectively. We found that astrocyte activation accompanying with serotonin receptor 2 A (5HTR2A) upregulation in the spinal cord was tightly associated with ALS-like pathology, which was effectively attenuated by DLT administration. We showed that DLT administration significantly delayed ALS symptom onset time, prolonged lifespan and ameliorated movement disorders, gastrocnemius injury and spinal motor neuronal loss in hSOD1[G93A] mice. Spinal cord-specific knockdown of 5HTR2A by intrathecal injection of adeno-associated virus9 (AAV9)-si-5Htr2a also ameliorated ALS pathology in hSOD1[G93A] mice, and occluded the therapeutic effects of DLT administration. Furthermore, we demonstrated that DLT administration promoted autophagy to reduce mutant hSOD1 levels through 5HTR2A/cAMP/AMPK pathway, suppressed oxidative stress through 5HTR2A/cAMP/AMPK/Nrf2-HO-1/NQO-1 pathway, and inhibited astrocyte neuroinflammation through 5HTR2A/cAMP/AMPK/NF-κB/NLRP3 pathway in the spinal cord of hSOD1[G93A] mice. In summary, 5HTR2A antagonism shows promise as a therapeutic strategy for ALS, highlighting the potential of DLT in the treatment of the disease. DLT as a 5HTR2A antagonist effectively promoted autophagy to reduce mutant hSOD1 level through 5HTR2A/cAMP/AMPK pathway, suppressed oxidative stress through 5HTR2A/cAMP/AMPK/Nrf2-HO-1/NQO-1 pathway, and inhibited astrocytic neuroinflammation through 5HTR2A/cAMP/AMPK/NF-κB/NLRP3 pathway in the spinal cord of hSOD1[G93A] mice.}, } @article {pmid38286389, year = {2024}, author = {Rayner, SL and Hogan, A and Davidson, JM and Chapman, T and Cheng, F and Luu, L and Wu, S and Zhang, S and Yang, S and Blair, I and Morsch, M and Chung, R and Lee, A}, title = {Cyclin F can alter the turnover of TDP-43.}, journal = {Neurobiology of disease}, volume = {192}, number = {}, pages = {106421}, doi = {10.1016/j.nbd.2024.106421}, pmid = {38286389}, issn = {1095-953X}, mesh = {Animals ; *Amyotrophic Lateral Sclerosis/metabolism ; Zebrafish ; DNA-Binding Proteins/metabolism ; Ubiquitination ; Cyclins/genetics/metabolism ; }, abstract = {Previously, we demonstrated that the SCF[cyclin F] complex directly mediates the poly-ubiquitylation of TDP-43, raising the question of whether cyclin F can be used to enhance the turnover of TDP-43. A hurdle to the use of cyclin F, however, is that the overexpression of cyclin F can lead to the initiation of cell death pathways. Accordingly, the aim of this study was to identify and evaluate a less toxic variant of cyclin F. To do so, we first confirmed and validated our previous findings that cyclin F binds to TDP-43 in an atypical manner. Additionally, we demonstrated that mutating the canonical substrate region in cyclin F (to generate cyclin F[MRL/AAA]) led to reduced binding affinity to known canonical substrates without impacting the interaction between cyclin F and TDP-43. Notably, both wild-type and cyclin F[MRL/AAA] effectively reduced the abundance of TDP-43 in cultured cells whilst cyclin F[MRL/AAA] also demonstrated reduced cell death compared to the wild-type control. The decrease in toxicity also led to a reduction in morphological defects in zebrafish embryos. These results suggest that cyclin F can be modified to enhance its targeting of TDP-43, which in turn reduces the toxicity associated with the overexpression of cyclin F. This study provides greater insights into the interaction that occurs between cyclin F and TDP-43 in cells and in vivo.}, } @article {pmid38286113, year = {2024}, author = {Dutta, A and Manna, A and Ghosh, S and Mundle, M and Saha, M and Gourav, K and Maiti, S and Chattopadhyay, B}, title = {Prespecified Homeopathic Medicines in the Prevention of Confirmed and Suspected Cases of COVID-19: A Community-Based, Double-Blind, Randomized, Placebo-Controlled Prophylaxis Trial.}, journal = {Complementary medicine research}, volume = {31}, number = {2}, pages = {140-148}, doi = {10.1159/000536395}, pmid = {38286113}, issn = {2504-2106}, mesh = {Humans ; Double-Blind Method ; *COVID-19/prevention & control ; Male ; Female ; Adult ; *Homeopathy/methods ; Middle Aged ; India/epidemiology ; *Materia Medica/therapeutic use ; SARS-CoV-2 ; *COVID-19 Drug Treatment ; }, abstract = {INTRODUCTION: Homeopathic medicines have been used for decades in the prevention and treatment of infectious diseases. However, the preventive efficacy of specific homeopathic medicines in COVID-19 is not well characterized. This study aimed to evaluate the comparative efficacy of prespecified homeopathic medicines in preventing COVID-19.

METHODS: A community-based, double-blind, randomized, placebo-controlled trial was conducted on 4,034 participants residing in Ward No. 27 of the Howrah Municipal Corporation in India. Participants were randomized to receive one of three prespecified homeopathic medicines [Influenzinum 30C, Arsenicum album 30C, Anas barbariae hepatis et cordis extractum 200K (Oscillococcinum®)], or placebo. The outcomes were the incidence of laboratory-confirmed and suspected cases of COVID-19 during a follow-up period of 1 month.

RESULTS: During the follow-up period, a total of 13 new laboratory-confirmed COVID-19 cases were reported in the study population. Among these, 5 cases in Influenzinum group, 2 cases in Arsenicum album group, 1 case in Oscillococcinum® group, and 5 cases in Placebo group were reported. On the other hand, number of suspected COVID-19 cases was significantly less in all the three homeopathic medicine groups compared to placebo. The least number of suspected cases reported in the Oscillococcinum® group (aOR: 0.058; 95% confidence interval [CI]: 0.029, 0.114), followed by the Arsenicum album (aOR: 0.337; 95% CI: 0.238, 0.475) and Influenzinum (aOR: 0.539; 95% CI: 0.401, 0.726) groups.

CONCLUSION: Prespecified homeopathic medicines, particularly Oscillococcinum® and Arsenicum album 30C, may have a role in preventing COVID-19, especially in reducing the incidence of suspected or COVID-19-like respiratory illnesses. However, the result failed to demonstrate a statistically significant difference in the occurrence of confirmed cases of COVID-19 between the study groups. Further research is needed to evaluate the efficacy of these medicines in different populations and settings.

UNLABELLED: EinleitungHomöopathische Arzneimittel werden seit Jahrzehnten zur Prävention und Behandlung von Infektionskrankheiten eingesetzt. Die Wirksamkeit spezifischer homöopathischer Arzneimittel zur Prophylaxe von COVID-19 ist jedoch nicht gut untersucht. Mit dieser Studie sollte die vergleichende Wirksamkeit spezifischer homöopathischer Arzneimittel bei der Prävention von COVID-19 untersucht werden.MethodenEs handelte sich um eine gemeindebasierte, doppelblinde, randomisierte, placebokontrollierte Studie mit 4.034 Teilnehmern, die im Bezirk Nr. 27 der Howrah Municipal Corporation in Indien lebten. Die Teilnehmer erhielten randomisiert eines von drei zuvor festgelegten homöopathischen Arzneimitteln [Influenzinum 30C, Arsenicum album 30C, Anas barbariae hepatis et cordis extractum 200K (Oscillococcinum®)] oder Placebo. Zielkriterien waren die Inzidenz von laborchemisch bestätigten und vermuteten COVID-19-Fällen während des Follow-up-Zeitraums von einem Monat.ErgebnisseWährend des Follow-up-Zeitraums wurden insgesamt 13 neue, laborchemisch bestätigte COVID-19-Fälle in der Studienpopulation berichtet, davon 5 Fälle in der Influenzinum-Gruppe, 2 Fälle in der Arsenicum album-Gruppe, 1 Fall in der Oscillococcinum®-Gruppe und 5 Fälle in der Placebo-Gruppe. Demgegenüber fiel Zahl der COVID-19-Verdachtsfälle in allen drei homöopathischen Arzneimittelgruppen signifikant geringer aus als in der Placebogruppe. Die wenigsten Verdachtsfälle wurden in der Oscillococcinum®-Gruppe berichtet (aOR: 0.058; 95%-KI: 0.029, 0.114), gefolgt von der Arsenicum album- (aOR: 0.337; 95%-KI: 0.238, 0.475) und der Influenzinum- (aOR: 0.539; 95%-KI: 0.401, 0.726) Gruppe.SchlussfolgerungSpezifische homöopathische Arzneimittel, insbesondere Oscillococcinum® und Arsenicum album 30C, könnten bei der Prävention von COVID-19 eine Rolle spielen, vor allem bei der Senkung der Inzidenz von COVID-19-Verdachtsfällen oder COVID-19-ähnlichen Atemwegserkrankungen. Allerdings war kein statistisch signifikanter Unterschied im Auftreten von bestätigten COVID-19-Fällen zwischen den Studiengruppen nachweisbar. Weitere Untersuchungen sind erforderlich, um die Wirksamkeit dieser Arzneimittel in verschiedenen Populationen und Umgebungen zu bewerten.}, } @article {pmid38286111, year = {2024}, author = {Wang, M and Wang, T and Gu, F}, title = {Efficacy of Huanglian Jiedu Decoction for Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis.}, journal = {Complementary medicine research}, volume = {31}, number = {2}, pages = {187-200}, doi = {10.1159/000536453}, pmid = {38286111}, issn = {2504-2106}, mesh = {*Diabetes Mellitus, Type 2/drug therapy ; Humans ; *Drugs, Chinese Herbal/therapeutic use ; Blood Glucose/drug effects ; Glycated Hemoglobin ; Randomized Controlled Trials as Topic ; *Hypoglycemic Agents/therapeutic use ; }, abstract = {OBJECTIVE: Type 2 diabetes mellitus (T2DM) is a prevalent metabolic disorder, and there is an increasing interest in the potential benefits of traditional Chinese medicine, such as Huanglian Jiedu decoction (HJD), for its management. This meta-analysis aimed to determine the efficacy and safety of HJD in the treatment of T2DM.

METHODS: A systematic review was conducted across six databases including PubMed, Embase, Cochrane, Web of Science, China National Knowledge Infrastructure (CNKI), and Wanfang, from their inception to August 24, 2023. We focused on randomized controlled trials (RCTs) that evaluated HJD as both a monotherapy and in combination treatments for T2DM patients. Data analysis was performed using RevMan 5.3 and Stata 17.0, with evaluations for heterogeneity and publication bias. Additionally, subgroup analyses were stratified based on the duration of treatment.

RESULTS: A total of 40 studies involving 3,934 participants were included in the meta-analysis. Both HJD monotherapy and combined with other therapies significantly reduced hemoglobin A1C (HbA1c) fasting blood glucose (FBG) and 2-h postprandial glucose (2hPG) levels, as well as improved insulin resistance. Furthermore, combination therapy enhanced the efficacy rate and favorably altered lipid profiles, including increasing HDL-C and decreasing LDL-C, TC, and TG levels. It was worth noting that the results of the subgroup analysis indicated that, in terms of reducing HbA1c and 2hPG, the efficacy of HJD alone for a duration of less than 3 months was found to be potentially superior to that observed in treatments exceeding 3 months. Adverse event assessment suggested that HJD did not increase the incidence of side effects, including diarrhea, affirming its safety.

CONCLUSION: HJD appears to be an effective and safe alternative or adjunctive therapy for T2DM, showing significant improvements in glycemic control and lipid profiles without increasing adverse events. Further rigorous, multicenter RCTs outside China are warranted to validate these findings.

UNLABELLED: ZielDiabetes mellitus Typ 2 (DMT2) ist eine weit verbreitete Stoffwechselerkrankung, und es besteht ein steigendes Interesse an den potenziellen Vorteilen der traditionellen chinesischen Medizin, wie beispielsweise Huanglian Jiedu-Dekokt (HJD), zu seiner Behandlung. Mit dieser Metaanalyse sollten die Wirksamkeit und Sicherheit von HJD zur Behandlung von DMT2 ermittelt werden.MethodenEs wurde eine systematische Recherche in sechs Datenbanken durchgeführt, darunter PubMed, Embase, Cochrane, Web of Science, China National Knowledge Infrastructure (CNKI) und Wanfang, für die Zeit vom Beginn der Datenbank bis zum 24. August 2023. Dabei lag unser Hauptaugenmerk auf randomisierten kontrollierten Studien (RCTs), die HJD sowohl als Monotherapie als auch in Kombinationstherapien bei Patienten mit DMT2 untersuchten. Die Datenanalyse erfolgte mithilfe von RevMan 5.3 und Stata 17.0 mit Untersuchungen auf Heterogenität und Publikationsverzerrungen. Darüber hinaus wurden Subgruppenanalysen stratifiziert nach Behandlungsdauer durchgeführt.ErgebnisseInsgesamt wurden 40 Studien mit 3.934 Teilnehmern in die Metaanalyse eingeschlossen. HJD führte sowohl als Monotherapie als auch in Kombination mit anderen Therapien zu einer signifikanten Senkung des HbA1c-Nüchternblutzuckerspiegels (fasting blood glucose, FBG) und der postprandialen Blutzuckerwerte 2 Stunden nach dem Essen (2-h postprandial glucose, 2hPG) sowie zu einer Verbesserung der Insulinresistenz. Darüber hinaus verbesserte die Kombinationstherapie die Wirksamkeitsrate und führte zu einer positiven Veränderung der Lipidprofile, die eine Erhöhung der HDL-Cholesterinwerte und eine Senkung der LDL-, Gesamtcholesterin- und Trigylceridwerte einschloss. Erwähnenswert ist, dass nach den Ergebnissen der Subgruppenanalyse die Wirksamkeit von HJD als Monotherapie in Hinblick auf die Senkung der HbA1c- und 2hPG-Werte bei einer Behandlungsdauer von weniger als drei Monaten gegenüber derjenigen von Behandlungen, die länger als drei Monate dauerten, potenziell überlegen war. Die Bewertung der unerwünschten Ereignisse zeigte, dass HJD nicht zu einem Anstieg der Nebenwirkungen wie Durchfall führte, was seine Sicherheit bestätigte.SchlussfolgerungHJD scheint eine wirksame und sichere Alternative oder Zusatztherapie bei DMT2 zu sein, die signifikante Verbesserungen der Blutzuckerkontrolle und der Lipidprofile ohne Zunahme der unerwünschten Ereignisse bewirkt. Weitere rigorose, multizentrische RCTs außerhalb Chinas sind erforderlich, um diese Ergebnisse zu validieren.}, } @article {pmid38285093, year = {2024}, author = {Díaz, M and Fabelo, N and Martín, MV and Santos, G and Ferrer, I}, title = {Evidence for alterations in lipid profiles and biophysical properties of lipid rafts from spinal cord in sporadic amyotrophic lateral sclerosis.}, journal = {Journal of molecular medicine (Berlin, Germany)}, volume = {102}, number = {3}, pages = {391-402}, pmid = {38285093}, issn = {1432-1440}, support = {SAF2014-52582-R//Ministerio de Ciencia e Innovación/ ; SAF2017-84454-R//Ministerio de Ciencia e Innovación/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism/pathology ; *Neurodegenerative Diseases/metabolism ; Lipids ; Membrane Microdomains/metabolism/pathology ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is an age-dependent neurodegenerative disease affecting motor neurons in the spinal cord and brainstem whose etiopathogenesis remains unclear. Recent studies have linked major neurodegenerative diseases with altered function of multimolecular lipid-protein complexes named lipid rafts. In the present study, we have isolated lipid rafts from the anterior horn of the spinal cords of controls and ALS individuals and analysed their lipid composition. We found that ALS affects levels of different fatty acids, lipid classes and related ratios and indexes. The most significant changes affected the contents of n-9/n-7 monounsaturated fatty acids and arachidonic acid, the main n-6 long-chain polyunsaturated fatty acid (LCPUFA), which were higher in ALS lipid rafts. Paralleling these findings, ALS lipid rafts lower saturates-to-unsaturates ratio compared to controls. Further, levels of cholesteryl ester (SE) and anionic-to-zwitterionic phospholipids ratio were augmented in ALS lipid rafts, while sulfatide contents were reduced. Further, regression analyses revealed augmented SE esterification to (mono)unsaturated fatty acids in ALS, but to saturates in controls. Overall, these changes indicate that lipid rafts from ALS spinal cord undergo destabilization of the lipid structure, which might impact their biophysical properties, likely leading to more fluid membranes. Indeed, estimations of membrane microviscosity confirmed less viscous membranes in ALS, as well as more mobile yet smaller lipid rafts compared to surrounding membranes. Overall, these results demonstrate that the changes in ALS lipid rafts are unrelated to oxidative stress, but to anomalies in lipid metabolism and/or lipid raft membrane biogenesis in motor neurons. KEY MESSAGES: The lipid matrix of multimolecular membrane complexes named lipid rafts are altered in human spinal cord in sporadic amyotrophic lateral sclerosis (ALS). Lipid rafts from ALS spinal cord contain higher levels of n-6 LCPUFA (but not n-3 LCPUFA), n-7/n-9 monounsaturates and lower saturates-to-unsaturates ratio. ALS lipid rafts display increased contents of cholesteryl esters, anomalous anionic-to-zwitterionic phospholipids and phospholipid remodelling and reduced sulphated and total sphingolipid levels, compared to control lipid rafts. Destabilization of the lipid structure of lipid raft affects their biophysical properties and leads to more fluid, less viscous membrane microdomains. The changes in ALS lipid rafts are unlikely related to increased oxidative stress, but to anomalies in lipid metabolism and/or raft membrane biogenesis in motor neurons.}, } @article {pmid38284771, year = {2024}, author = {Grassano, M and Koumantakis, E and Manera, U and Canosa, A and Vasta, R and Palumbo, F and Fuda, G and Salamone, P and Marchese, G and Casale, F and Charrier, L and Mora, G and Moglia, C and Calvo, A and Chiò, A}, title = {Giving Breath to Motor Neurons: Noninvasive Mechanical Ventilation Slows Disease Progression in Amyotrophic Lateral Sclerosis.}, journal = {Annals of neurology}, volume = {95}, number = {4}, pages = {817-822}, doi = {10.1002/ana.26875}, pmid = {38284771}, issn = {1531-8249}, support = {2017SNW5MB//Ministero dell'Istruzione, dell'Università e della Ricerca/ ; 259867//Seventh Framework Programme/ ; RF-2016-02362405//Ministero della Salute/ ; //EU Joint Programme - Neurodegenerative Disease Research/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis ; Respiration, Artificial ; Disease Progression ; Quality of Life ; Motor Neurons ; }, abstract = {OBJECTIVE: Noninvasive mechanical ventilation (NIMV) improves amyotrophic lateral sclerosis (ALS) quality of life and survival. However, data about its effect on disease progression are still lacking. Here, we test whether NIMV use changed the rate of functional decline among ALS patients.

METHODS: In this retrospective observational study, we included 448 ALS patients followed up at the ALS Center in Turin, Italy, who underwent NIMV during the disease course. The primary outcome was the change in functional decline after NIMV initiation adjusting for covariates. Functional decline was based on the nonrespiratory items of the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R).

RESULTS: NIMV initiation resulted in a slower functional decline (mean improvement = 0.16 points per month, 95% confidence interval = 0.12-0.19, p < 0.001), with consistent effects observed across various demographic factors, including sex, age at diagnosis, and disease duration before NIMV initiation. This finding was replicated using the PRO-ACT (Pooled Resource Open-Access ALS Clinical Trials) dataset. The favorable impact of NIMV on ALSFRS-R progression was evident independently of disease stages. Notably, NIMV benefits were not dose-dependent but were particularly prominent for nighttime respiratory support.

INTERPRETATION: NIMV significantly influences the rate of motor progression in ALS, and this effect is not determined by the nonlinearity of ALSFRS-R trajectory. The functional decline slowed following NIMV initiation, independently of the site of disease onset or disease severity at the time of NIMV initiation. Our findings underscore the importance of timely NIMV initiation for all ALS patients and highlight the need to consider NIMV-induced slowing of disease progression when evaluating clinical trial outcomes. ANN NEUROL 2024;95:817-822.}, } @article {pmid38284068, year = {2024}, author = {Sunildutt, N and Ahmed, F and Chethikkattuveli Salih, AR and Lim, JH and Choi, KH}, title = {Integrating Transcriptomic and Structural Insights: Revealing Drug Repurposing Opportunities for Sporadic ALS.}, journal = {ACS omega}, volume = {9}, number = {3}, pages = {3793-3806}, pmid = {38284068}, issn = {2470-1343}, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive and devastating neurodegenerative disorder characterized by the loss of upper and lower motor neurons, resulting in debilitating muscle weakness and atrophy. Currently, there are no effective treatments available for ALS, posing significant challenges in managing the disease that affects approximately two individuals per 100,000 people annually. To address the urgent need for effective ALS treatments, we conducted a drug repurposing study using a combination of bioinformatics tools and molecular docking techniques. We analyzed sporadic ALS-related genes from the GEO database and identified key signaling pathways involved in sporadic ALS pathogenesis through pathway analysis using DAVID. Subsequently, we utilized the Clue Connectivity Map to identify potential drug candidates and performed molecular docking using AutoDock Vina to evaluate the binding affinity of short-listed drugs to key sporadic ALS-related genes. Our study identified Cefaclor, Diphenidol, Flubendazole, Fluticasone, Lestaurtinib, Nadolol, Phenamil, Temozolomide, and Tolterodine as potential drug candidates for repurposing in sporadic ALS treatment. Notably, Lestaurtinib demonstrated high binding affinity toward multiple proteins, suggesting its potential as a broad-spectrum therapeutic agent for sporadic ALS. Additionally, docking analysis revealed NOS3 as the gene that interacts with all the short-listed drugs, suggesting its possible involvement in the mechanisms underlying the therapeutic potential of these drugs in sporadic ALS. Overall, our study provides a systematic framework for identifying potential drug candidates for sporadic ALS therapy and highlights the potential of drug repurposing as a promising strategy for discovering new therapies for neurodegenerative diseases.}, } @article {pmid38283093, year = {2023}, author = {Calderón-Garcidueñas, L and Stommel, EW and Torres-Jardón, R and Hernández-Luna, J and Aiello-Mora, M and González-Maciel, A and Reynoso-Robles, R and Pérez-Guillé, B and Silva-Pereyra, HG and Tehuacanero-Cuapa, S and Rodríguez-Gómez, A and Lachmann, I and Galaz-Montoya, C and Doty, RL and Roy, A and Mukherjee, PS}, title = {Alzheimer and Parkinson diseases, frontotemporal lobar degeneration and amyotrophic lateral sclerosis overlapping neuropathology start in the first two decades of life in pollution exposed urbanites and brain ultrafine particulate matter and industrial nanoparticles, including Fe, Ti, Al, V, Ni, Hg, Co, Cu, Zn, Ag, Pt, Ce, La, Pr and W are key players. Metropolitan Mexico City health crisis is in progress.}, journal = {Frontiers in human neuroscience}, volume = {17}, number = {}, pages = {1297467}, pmid = {38283093}, issn = {1662-5161}, abstract = {The neuropathological hallmarks of Alzheimer's disease (AD), Parkinson's disease (PD), frontotemporal lobar degeneration (FTLD), and amyotrophic lateral sclerosis (ALS) are present in urban children exposed to fine particulate matter (PM2.5), combustion and friction ultrafine PM (UFPM), and industrial nanoparticles (NPs). Metropolitan Mexico City (MMC) forensic autopsies strongly suggest that anthropogenic UFPM and industrial NPs reach the brain through the nasal/olfactory, lung, gastrointestinal tract, skin, and placental barriers. Diesel-heavy unregulated vehicles are a key UFPM source for 21.8 million MMC residents. We found that hyperphosphorylated tau, beta amyloid1-42, α-synuclein, and TAR DNA-binding protein-43 were associated with NPs in 186 forensic autopsies (mean age 27.45 ± 11.89 years). The neurovascular unit is an early NPs anatomical target, and the first two decades of life are critical: 100% of 57 children aged 14.8 ± 5.2 years had AD pathology; 25 (43.9%) AD+TDP-43; 11 (19.3%) AD + PD + TDP-43; and 2 (3.56%) AD +PD. Fe, Ti, Hg, Ni, Co, Cu, Zn, Cd, Al, Mg, Ag, Ce, La, Pr, W, Ca, Cl, K, Si, S, Na, and C NPs are seen in frontal and temporal lobes, olfactory bulb, caudate, substantia nigra, locus coeruleus, medulla, cerebellum, and/or motor cortical and spinal regions. Endothelial, neuronal, and glial damages are extensive, with NPs in mitochondria, rough endoplasmic reticulum, the Golgi apparatus, and lysosomes. Autophagy, cell and nuclear membrane damage, disruption of nuclear pores and heterochromatin, and cell death are present. Metals associated with abrasion and deterioration of automobile catalysts and electronic waste and rare earth elements, i.e., lanthanum, cerium, and praseodymium, are entering young brains. Exposure to environmental UFPM and industrial NPs in the first two decades of life are prime candidates for initiating the early stages of fatal neurodegenerative diseases. MMC children and young adults-surrogates for children in polluted areas around the world-exhibit early AD, PD, FTLD, and ALS neuropathological hallmarks forecasting serious health, social, economic, academic, and judicial societal detrimental impact. Neurodegeneration prevention should be a public health priority as the problem of human exposure to particle pollution is solvable. We are knowledgeable of the main emission sources and the technological options to control them. What are we waiting for?}, } @article {pmid38282082, year = {2024}, author = {Parnianpour, P and Benatar, M and Briemberg, H and Dey, A and Dionne, A and Dupré, N and Evans, KC and Frayne, R and Genge, A and Graham, SJ and Korngut, L and McLaren, DG and Seres, P and Welsh, RC and Wilman, A and Zinman, L and Kalra, S}, title = {Mismatch between clinically defined classification of ALS stage and the burden of cerebral pathology.}, journal = {Journal of neurology}, volume = {271}, number = {5}, pages = {2547-2559}, pmid = {38282082}, issn = {1432-1459}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnostic imaging/pathology ; Male ; Female ; Middle Aged ; *Disease Progression ; Aged ; *Magnetic Resonance Imaging ; Adult ; Brain/diagnostic imaging/pathology ; Severity of Illness Index ; Longitudinal Studies ; Cerebral Cortex/diagnostic imaging/pathology ; }, abstract = {This study aimed to investigate the clinical stratification of amyotrophic lateral sclerosis (ALS) patients in relation to in vivo cerebral degeneration. One hundred forty-nine ALS patients and one hundred forty-four healthy controls (HCs) were recruited from the Canadian ALS Neuroimaging Consortium (CALSNIC). Texture analysis was performed on T1-weighted scans to extract the texture feature "autocorrelation" (autoc), an imaging biomarker of cerebral degeneration. Patients were stratified at baseline into early and advanced disease stages based on criteria adapted from ALS clinical trials and the King's College staging system, as well as into slow and fast progressors (disease progression rates, DPR). Patients had increased autoc in the internal capsule. These changes extended beyond the internal capsule in early-stage patients (clinical trial-based criteria), fast progressors, and in advanced-stage patients (King's staging criteria). Longitudinal increases in autoc were observed in the postcentral gyrus, corticospinal tract, posterior cingulate cortex, and putamen; whereas decreases were observed in corpus callosum, caudate, central opercular cortex, and frontotemporal areas. Both longitudinal increases and decreases of autoc were observed in non-overlapping regions within insula and precentral gyrus. Within-criteria comparisons of autoc revealed more pronounced changes at baseline and longitudinally in early- (clinical trial-based criteria) and advanced-stage (King's staging criteria) patients and fast progressors. In summary, comparative patterns of baseline and longitudinal progression in cerebral degeneration are dependent on sub-group selection criteria, with clinical trial-based stratification insufficiently characterizing disease stage based on pathological cerebral burden.}, } @article {pmid38281010, year = {2024}, author = {Fouda, AES and Etaiw, SEH and Abd El-Aziz, DM and El-Hossiany, AA and Elbaz, UA}, title = {Experimental and theoretical studies of the efficiency of metal-organic frameworks (MOFs) in preventing aluminum corrosion in hydrochloric acid solution.}, journal = {BMC chemistry}, volume = {18}, number = {1}, pages = {21}, pmid = {38281010}, issn = {2661-801X}, abstract = {Aluminum corrosion inhibitors "{[CuI (CN)2(phen) CuII (CN)2(phen)]5H2O}, (MOF1) and {[CuI(CN)2(phen)CuII(CN)2(phen)]5H2O} @TiO2 (MOF1@TiO2) were studied in one molar HCl solution". The ML results for three different temperatures (25-45 °C) were compared with the results of PDP and EIS analyses. The adsorption of inhibitors on Al surfaces has been calculated and discussed by a Langmuir isotherm. The inhibitors that were created showed great effectiveness, with a noticeable increase in their inhibitory efficiency as the dosage was raised and the temperature was lowered. Inhibition efficiency each amounted to 88.6%, 84.5% at 400 ppm and 25 °C for MOF1@TiO2 and MOF1, respectively. Analyzing the polarization curves of synthesized inhibitors revealed that they were mixed-type inhibitors. Al was found to be surface inhibited when coated with a thin film of inhibitors, and "Al's surface morphology was assessed by different techniques such as scanning electron microscopy (SEM), energy dispersive X-ray (EDX) and atomic force microscope (AFM)". "Theoretical models like quantum chemical and molecular dynamics simulation authenticated the experimental observation". The MOFs exhibit exceptional corrosion resistance against Al when exposed to acidic environments, according to several tests.}, } @article {pmid38280780, year = {2024}, author = {Karimvand, SK and Pahlevan, A and Zade, SV and Jafari, JM and Abdollahi, H}, title = {Multivariate curve resolution-soft independent modelling of class analogy (MCR-SIMCA).}, journal = {Analytica chimica acta}, volume = {1291}, number = {}, pages = {342205}, doi = {10.1016/j.aca.2024.342205}, pmid = {38280780}, issn = {1873-4324}, abstract = {BACKGROUND: Various classification, class modeling, and clustering techniques operate within abstract spaces, utilizing Principal Components (e.g., Linear Discriminant Analysis (LDA), Principal Component Analysis (PCA)) or latent variable spaces (e.g., Partial Least Squares Discriminant Analysis (PLS-DA)). It's important to note that PCA, despite being a mathematical tool, defines its Principal Components under certain mathematical constraints, it has a wide range of applications in the analysis of real-world systems. In this research, we assess the viability of employing the Multivariate Curve Resolution (MCR) subspace within class modeling techniques, as an alternative to the PC subspace. (92).

RESULTS: This study evaluates the use of the MCR subspace in class modeling methods, specifically in tandem with soft independent modeling of class analogy (SIMCA), to investigate the advantages of employing the meaningful physico-chemical subspace of MCR over the mathematical subspace of PCA. In the MCR-SIMCA strategy, the model is constructed by applying MCR to training samples from a target class. The MCR model effectively partitions the data into two smaller sub-matrices: the contribution matrix and the corresponding response matrix. In the next step, the contribution matrix resulting from the decomposition of the training set develops a distance plot (DP). First, the theory of the MCR-SIMCA model is discussed in detail. Next, two real experimental datasets were analyzed, and their performance was compared with the DD-SIMCA model. In most cases, the results were as good as or even more satisfactory than those obtained with the DD-SIMCA model. (146).

SIGNIFICANCE: The suggested class modeling method presents a promising avenue for the analysis of real-world natural systems. The study's results emphasize the practical utility of the MCR approach, underscoring the significance of the MCR subspace advantages over the PCA subspace. (39).}, } @article {pmid38279584, year = {2024}, author = {Lai, C and Chuang, LH and Lai, CC and Liu, CF and Yang, JW and Chen, HSL}, title = {Longitudinal changes in optical coherence tomography angiography characteristics in normal-tension glaucoma with or without high myopia.}, journal = {Acta ophthalmologica}, volume = {102}, number = {5}, pages = {e762-e773}, doi = {10.1111/aos.16644}, pmid = {38279584}, issn = {1755-3768}, mesh = {Humans ; *Tomography, Optical Coherence/methods ; *Low Tension Glaucoma/physiopathology/diagnosis ; Male ; Female ; *Visual Fields/physiology ; Middle Aged ; *Fluorescein Angiography/methods ; *Retinal Ganglion Cells/pathology ; *Nerve Fibers/pathology ; *Intraocular Pressure/physiology ; *Optic Disk/blood supply ; Retinal Vessels/diagnostic imaging/pathology ; Aged ; Follow-Up Studies ; Disease Progression ; Myopia, Degenerative/physiopathology/diagnosis/complications ; Retrospective Studies ; Fundus Oculi ; }, abstract = {PURPOSE: To evaluate the structural, microvascular, and functional progression of normal tension glaucoma (NTG) with or without high myopia by examining longitudinal changes in optical coherence tomography angiography (OCTA) and visual field (VF) parameters.

METHODS: We evaluated 61 NTG eyes and classified 25 of the eyes with axial lengths (ALs) of ≥26 mm as highly myopic. We assessed the rate of change in OCTA parameters, namely radial peripapillary capillary (RPC) vessel density (VD), parafovea VD, deep parafovea VD, retinal nerve fibre layer (RNFL) thickness, and ganglion cell complex thickness. We evaluated the correlation of the rate of change in OCTA parameters with VF loss and AL.

RESULTS: Among the 61 NTG eyes, rates of loss of RPC VD, parafovea VD, deep parafovea VD, and RNFL thickness were significantly different from zero despite the nonsignificant rate of change in VF mean deviation (MD). Changes in these OCTA parameters did not differ significantly in highly myopic NTG eyes. The rate of change in VF MD was significantly correlated with the rate of change in parafovea VD in highly myopic and non-highly myopic NTG eyes. In highly myopic NTG eyes, AL was negatively correlated with the rates of loss of RNFL thickness, VF MD, and VF PSD.

CONCLUSION: NTG eyes with a relatively stable VF exhibited loss of VD and RNFL thickness. VF progression in NTG was correlated with decreasing parafovea VD, indicating a structure-function correlation. Greater AL may indicate faster VF loss and RNFL thinning in highly myopic NTG eyes.}, } @article {pmid38278991, year = {2024}, author = {Irwin, KE and Jasin, P and Braunstein, KE and Sinha, IR and Garret, MA and Bowden, KD and Chang, K and Troncoso, JC and Moghekar, A and Oh, ES and Raitcheva, D and Bartlett, D and Miller, T and Berry, JD and Traynor, BJ and Ling, JP and Wong, PC}, title = {A fluid biomarker reveals loss of TDP-43 splicing repression in presymptomatic ALS-FTD.}, journal = {Nature medicine}, volume = {30}, number = {2}, pages = {382-393}, pmid = {38278991}, issn = {1546-170X}, support = {T32 GM136577/GM/NIGMS NIH HHS/United States ; R33 NS115161/NS/NINDS NIH HHS/United States ; ZIA AG000933/ImNIH/Intramural NIH HHS/United States ; RF1 NS095969/NS/NINDS NIH HHS/United States ; R01 NS095969/NS/NINDS NIH HHS/United States ; P30 AG066507/AG/NIA NIH HHS/United States ; U01 FD008129/FD/FDA HHS/United States ; UH3 NS115608/NS/NINDS NIH HHS/United States ; }, mesh = {Humans ; *Frontotemporal Dementia/genetics ; *Amyotrophic Lateral Sclerosis/genetics ; C9orf72 Protein/genetics ; DNA-Binding Proteins/genetics/metabolism ; Biomarkers/cerebrospinal fluid ; }, abstract = {Although loss of TAR DNA-binding protein 43 kDa (TDP-43) splicing repression is well documented in postmortem tissues of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), whether this abnormality occurs during early-stage disease remains unresolved. Cryptic exon inclusion reflects loss of function of TDP-43, and thus detection of proteins containing cryptic exon-encoded neoepitopes in cerebrospinal fluid (CSF) or blood could reveal the earliest stages of TDP-43 dysregulation in patients. Here we use a newly characterized monoclonal antibody specific to a TDP-43-dependent cryptic epitope (encoded by the cryptic exon found in HDGFL2) to show that loss of TDP-43 splicing repression occurs in ALS-FTD, including in presymptomatic C9orf72 mutation carriers. Cryptic hepatoma-derived growth factor-like protein 2 (HDGFL2) accumulates in CSF at significantly higher levels in familial ALS-FTD and sporadic ALS compared with controls and is elevated earlier than neurofilament light and phosphorylated neurofilament heavy chain protein levels in familial disease. Cryptic HDGFL2 can also be detected in blood of individuals with ALS-FTD, including in presymptomatic C9orf72 mutation carriers, and accumulates at levels highly correlated with those in CSF. Our findings indicate that loss of TDP-43 cryptic splicing repression occurs early in disease progression, even presymptomatically, and that detection of the HDGFL2 cryptic neoepitope serves as a potential diagnostic biomarker for ALS, which should facilitate patient recruitment and measurement of target engagement in clinical trials.}, } @article {pmid38278691, year = {2024}, author = {Kwon, Y and Kang, M and Jeon, YM and Lee, S and Lee, HW and Park, JS and Kim, HJ}, title = {Identification and characterization of novel ERBB4 variant associated with sporadic amyotrophic lateral sclerosis (ALS).}, journal = {Journal of the neurological sciences}, volume = {457}, number = {}, pages = {122885}, doi = {10.1016/j.jns.2024.122885}, pmid = {38278691}, issn = {1878-5883}, mesh = {Male ; Humans ; Middle Aged ; *Amyotrophic Lateral Sclerosis/metabolism ; Mutation/genetics ; Receptor, ErbB-4/genetics/metabolism ; Tyrosine ; }, abstract = {Amyotrophic Lateral Sclerosis (ALS) is the most common type of motor neuron disease characterized by progressive motor neuron degeneration in brain and spinal cord. Most cases are sporadic in ALS and 5-10% of cases are familiar. >50 genes are known to be associated with ALS and one of them is ERBB4. In this paper, we report the case of a 53-year-old ALS patient with progressive muscle weakness and fasciculation, but he had no cognitive decline. We performed the next generation sequencing (NGS) and in silico analysis, it predicted a highly pathogenic variant, c.2116 A > G, p.Asn706Asp (N706D) in the ERBB4 gene. The amino acid residue is highly conserved among species. ERBB4 is a member of the ERBB family of receptor tyrosine kinases. ERBB4 has multiple tyrosine phosphorylation sites, including an autophosphorylation site at tyrosine 1284 residue. Autophosphorylation of ERBB4 promotes biological activity and it associated with NRG-1/ERBB4 pathway. It is already known that tyrosine 128 phosphorylation of ERBB4 is decreased in patients who have ALS-associated ERBB4 mutations. We generated ERBB4 N706D construct using site-directed mutagenesis and checked the phosphorylation level of ERBB4 N706D in NSC-34 cells. We found that the phosphorylation of ERBB4 N706D was decreased compared to ERBB4 wild-type, indicating a loss of function mutation in ERBB4. We report a novel variant in ERBB4 gene leading to ALS through dysfunction of ERBB4.}, } @article {pmid38278093, year = {2024}, author = {Goutman, SA and Boss, J and Jang, DG and Piecuch, C and Farid, H and Batra, M and Mukherjee, B and Feldman, EL and Batterman, SA}, title = {Avocational exposure associations with ALS risk, survival, and phenotype: A Michigan-based case-control study.}, journal = {Journal of the neurological sciences}, volume = {457}, number = {}, pages = {122899}, pmid = {38278093}, issn = {1878-5883}, support = {R01 TS000327/TS/ATSDR CDC HHS/United States ; R01TS000344/ACL/ACL HHS/United States ; K23 ES027221/ES/NIEHS NIH HHS/United States ; R01 ES030049/ES/NIEHS NIH HHS/United States ; P30 ES017885/ES/NIEHS NIH HHS/United States ; UL1 TR002240/TR/NCATS NIH HHS/United States ; R01 NS127188/NS/NINDS NIH HHS/United States ; R01 TS000344/TS/ATSDR CDC HHS/United States ; }, mesh = {Humans ; Middle Aged ; Case-Control Studies ; Michigan/epidemiology ; Risk Factors ; *Environmental Exposure ; Phenotype ; *Amyotrophic Lateral Sclerosis/epidemiology ; }, abstract = {INTRODUCTION: Environmental exposures strongly influence ALS risk and identification is needed to reduce ALS burden. Participation in hobbies and exercise may alter ALS risk and phenotype, warranting an assessment to understand their contribution to the ALS exposome.

METHODS: Participants with ALS and healthy controls were recruited from University of Michigan and self-completed a survey to ascertain hobbies, exercise, and avocational exposures. Exposure variables were associated with ALS risk, survival, onset segment, and onset age.

RESULTS: ALS (n = 400) and control (n = 287) participants self-reported avocational activities. Cases were slightly older (median age 63.0 vs. 61.1 years, p = 0.019) and had a lower educational attainment (p < 0.001) compared to controls; otherwise, demographics were well balanced. Risks associating with ALS after multiple comparison correction included golfing (odds ratio (OR) 3.48, padjusted = 0.004), recreational dancing (OR 2.00, padjusted = 0.040), performing gardening or yard work (OR 1.71, padjusted = 0.040) five years prior to ALS and personal (OR 1.76, padjusted = 0.047) or family (OR 2.21, padjusted = 0.040) participation in woodworking, and personal participation in hunting and shooting (OR 1.89, padjusted = 0.040). No exposures associated with ALS survival and onset. Those reporting swimming (3.86 years, padjusted = 0.016) and weightlifting (3.83 years, padjusted = 0.020) exercise 5 years prior to ALS onset had an earlier onset age.

DISCUSSION: The identified exposures in this study may represent important modifiable ALS factors that influence ALS phenotype. Thus, exposures related to hobbies and exercise should be captured in studies examining the ALS exposome.}, } @article {pmid38277781, year = {2024}, author = {Hirsch, E and Bornemissza, Z and Nagy, ZK and Marosi, GJ and Farkas, A}, title = {Quantitative and qualitative analysis of cell culture media powders for mammalian cells by Raman microscopy.}, journal = {Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy}, volume = {310}, number = {}, pages = {123906}, doi = {10.1016/j.saa.2024.123906}, pmid = {38277781}, issn = {1873-3557}, mesh = {Animals ; Powders ; *Microscopy ; *Cell Culture Techniques/methods ; Recombinant Proteins ; Least-Squares Analysis ; Spectrum Analysis, Raman/methods ; Culture Media/chemistry ; Multivariate Analysis ; Mammals ; }, abstract = {Cell culture media are essential for large-scale recombinant protein production using mammalian cell cultures. The composition and quality of media significantly impact cell growth and product formation. Analyzing media poses challenges due to complex compositions and undisclosed exact compositions. Traditional methods like NMR and chromatography offer sensitivity but require time-consuming sample preparation and lack spatial information. Raman chemical mapping characterizes solids, but its use in cell culture media analysis is limited so far. We present a chemometric evaluation for Raman maps to qualify and quantify media components, evaluate powder homogeneity, and perform lot-to-lot comparisons. Three lots of a marketed cell culture media powder were measured with Raman mapping technique. Chemometrics techniques have outlined a strategy to extract information from complex data. First, a spectral library has been structured. In addition to the 23 spectra for presumed ingredients, we obtained another 9 pure components with Multivariate Curve Resolution-Alternating Least Squares (MCR-ALS). Then the Spectral Angle Mapper-Orthogonal Projection (SAM-OP) algorithm revealed whether references actually occur in the mapped media powders. Finally, a quantification was provided by Classical Least Squares (CLS) modelling. Quantities of 18 significant amino acids mostly correlated with the reference method. The proposed method can be generally applied even for such complicated samples. Leveraging Raman mapping and innovative chemometric methods enhance recombinant protein production by improving the understanding of the spatial distribution and composition of cell culture media in mammalian cell cultivations.}, } @article {pmid38277467, year = {2024}, author = {Seddighi, S and Qi, YA and Brown, AL and Wilkins, OG and Bereda, C and Belair, C and Zhang, YJ and Prudencio, M and Keuss, MJ and Khandeshi, A and Pickles, S and Kargbo-Hill, SE and Hawrot, J and Ramos, DM and Yuan, H and Roberts, J and Sacramento, EK and Shah, SI and Nalls, MA and Colón-Mercado, JM and Reyes, JF and Ryan, VH and Nelson, MP and Cook, CN and Li, Z and Screven, L and Kwan, JY and Mehta, PR and Zanovello, M and Hallegger, M and Shantaraman, A and Ping, L and Koike, Y and Oskarsson, B and Staff, NP and Duong, DM and Ahmed, A and Secrier, M and Ule, J and Jacobson, S and Reich, DS and Rohrer, JD and Malaspina, A and Dickson, DW and Glass, JD and Ori, A and Seyfried, NT and Maragkakis, M and Petrucelli, L and Fratta, P and Ward, ME}, title = {Mis-spliced transcripts generate de novo proteins in TDP-43-related ALS/FTD.}, journal = {Science translational medicine}, volume = {16}, number = {734}, pages = {eadg7162}, pmid = {38277467}, issn = {1946-6242}, support = {R35 NS097273/NS/NINDS NIH HHS/United States ; RF1 AG062171/AG/NIA NIH HHS/United States ; T32 GM136577/GM/NIGMS NIH HHS/United States ; MC_PC_MR/S022708/1/MRC_/Medical Research Council/United Kingdom ; U19 AG063911/AG/NIA NIH HHS/United States ; CC0102/WT_/Wellcome Trust/United Kingdom ; MR/J009482/1/MRC_/Medical Research Council/United Kingdom ; P30 AG062677/AG/NIA NIH HHS/United States ; U54 NS123743/NS/NINDS NIH HHS/United States ; ZIA NS003155/ImNIH/Intramural NIH HHS/United States ; MR/T046015/1/MRC_/Medical Research Council/United Kingdom ; MR/M008525/1/MRC_/Medical Research Council/United Kingdom ; MR/W005190/1/MRC_/Medical Research Council/United Kingdom ; FI2 GM142475/GM/NIGMS NIH HHS/United States ; MR/S006508/1/MRC_/Medical Research Council/United Kingdom ; MALASPINA/APR13/817-791/MNDA_/Motor Neurone Disease Association/United Kingdom ; HALLEGGER/OCT15/959-799/MNDA_/Motor Neurone Disease Association/United Kingdom ; RF1 AG062077/AG/NIA NIH HHS/United States ; MR/M023664/1/MRC_/Medical Research Council/United Kingdom ; P01 NS084974/NS/NINDS NIH HHS/United States ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics ; DNA-Binding Proteins/genetics/metabolism ; *Frontotemporal Dementia/genetics ; Peptides ; Proteomics ; }, abstract = {Functional loss of TDP-43, an RNA binding protein genetically and pathologically linked to amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), leads to the inclusion of cryptic exons in hundreds of transcripts during disease. Cryptic exons can promote the degradation of affected transcripts, deleteriously altering cellular function through loss-of-function mechanisms. Here, we show that mRNA transcripts harboring cryptic exons generated de novo proteins in TDP-43-depleted human iPSC-derived neurons in vitro, and de novo peptides were found in cerebrospinal fluid (CSF) samples from patients with ALS or FTD. Using coordinated transcriptomic and proteomic studies of TDP-43-depleted human iPSC-derived neurons, we identified 65 peptides that mapped to 12 cryptic exons. Cryptic exons identified in TDP-43-depleted human iPSC-derived neurons were predictive of cryptic exons expressed in postmortem brain tissue from patients with TDP-43 proteinopathy. These cryptic exons produced transcript variants that generated de novo proteins. We found that the inclusion of cryptic peptide sequences in proteins altered their interactions with other proteins, thereby likely altering their function. Last, we showed that 18 de novo peptides across 13 genes were present in CSF samples from patients with ALS/FTD spectrum disorders. The demonstration of cryptic exon translation suggests new mechanisms for ALS/FTD pathophysiology downstream of TDP-43 dysfunction and may provide a potential strategy to assay TDP-43 function in patient CSF.}, } @article {pmid38276084, year = {2024}, author = {Vacchiano, V and Bonan, L and Liguori, R and Rizzo, G}, title = {Primary Lateral Sclerosis: An Overview.}, journal = {Journal of clinical medicine}, volume = {13}, number = {2}, pages = {}, pmid = {38276084}, issn = {2077-0383}, abstract = {Primary lateral sclerosis (PLS) is a rare neurodegenerative disorder which causes the selective deterioration of the upper motor neurons (UMNs), sparing the lower motor neuron (LMN) system. The clinical course is defined by a progressive motor disability due to muscle spasticity which typically involves lower extremities and bulbar muscles. Although classically considered a sporadic disease, some familiar cases and possible causative genes have been reported. Despite it having been recognized as a rare but distinct entity, whether it actually represents an extreme end of the motor neuron diseases continuum is still an open issue. The main knowledge gap is the lack of specific biomarkers to improve the clinical diagnostic accuracy. Indeed, the diagnostic imprecision, together with some uncertainty about overlap with UMN-predominant ALS and Hereditary Spastic Paraplegia (HSP), has become an obstacle to the development of specific therapeutic trials. In this study, we provided a comprehensive analysis of the existing literature, including neuropathological, clinical, neuroimaging, and neurophysiological features of the disease, and highlighting the controversies still unsolved in the differential diagnoses and the current diagnostic criteria. We also discussed the current knowledge gaps still present in both diagnostic and therapeutic fields when approaching this rare condition.}, } @article {pmid38274887, year = {2023}, author = {Ito, M and Fujii, N and Kohara, S and Tanaka, M and Takao, M and Mihara, B and Saito, Y and Mizuma, A and Nakayama, T and Netsu, S and Suzuki, N and Kakita, A and Nagata, E}, title = {Elevation of inositol pyrophosphate IP7 in the mammalian spinal cord of amyotrophic lateral sclerosis.}, journal = {Frontiers in neurology}, volume = {14}, number = {}, pages = {1334004}, pmid = {38274887}, issn = {1664-2295}, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder associated with progressive impairment of spinal motor neurons. Continuous research endeavor is underway to fully understand the molecular mechanisms associating with this disorder. Although several studies have implied the involvement of inositol pyrophosphate IP7 in ALS, there is no direct experimental evidence proving this notion. In this study, we analyzed inositol pyrophosphate IP7 and its precursor IP6 in the mouse and human ALS biological samples to directly assess whether IP7 level and/or its metabolism are altered in ALS disease state.

METHODS: We used a liquid chromatography-mass spectrometry (LC-MS) protocol originally-designed for mammalian IP6 and IP7 analysis. We measured the abundance of these molecules in the central nervous system (CNS) of ALS mouse model SOD1(G93A) transgenic (TG) mice as well as postmortem spinal cord of ALS patients. Cerebrospinal fluid (CSF) and peripheral blood mononuclear cells (PBMCs) from ALS patients were also analyzed to assess if IP7 status in these biofluids is associated with ALS disease state.

RESULTS: SOD1(G93A) TG mice showed significant increase of IP7 level in the spinal cord compared with control mice at the late stage of disease progression, while its level in cerebrum and cerebellum remains constant. We also observed significantly elevated IP7 level and its product-to-precursor ratio (IP7/IP6) in the postmortem spinal cord of ALS patients, suggesting enhanced enzymatic activity of IP7-synthesizing kinases in the human ALS spinal cord. In contrast, human CSF did not contain detectable level of IP6 and IP7, and neither the IP7 level nor the IP7/IP6 ratio in human PBMCs differentiated ALS patients from age-matched healthy individuals.

CONCLUSION: By directly analyzing IP7 in the CNS of ALS mice and humans, the findings of this study provide direct evidence that IP7 level and/or the enzymatic activity of IP7-generating kinases IP6Ks are elevated in ALS spinal cord. On the other hand, this study also showed that IP7 is not suitable for biofluid-based ALS diagnosis. Further investigation is required to elucidate a role of IP7 in ALS pathology and utilize IP7 metabolism on the diagnostic application of ALS.}, } @article {pmid38271732, year = {2024}, author = {Sample, C and Rahmim, A and Benard, F and Wu, J and Clark, H}, title = {PSMA PET/CT as a predictive tool for subregional importance estimates in the parotid gland.}, journal = {Biomedical physics & engineering express}, volume = {10}, number = {2}, pages = {}, doi = {10.1088/2057-1976/ad229c}, pmid = {38271732}, issn = {2057-1976}, mesh = {Humans ; Head ; *Parotid Gland/diagnostic imaging ; *Positron Emission Tomography Computed Tomography ; Positron-Emission Tomography ; }, abstract = {Objective. Xerostomia and radiation-induced salivary gland dysfunction remain a common side effect for head-and-neck radiotherapy patients, and attempts have been made to quantify the heterogeneity of the dose response within parotid glands. Prostate Specific Membrane Antigen (PSMA) ligands have demonstrated high uptake in salivary glands, which has been shown to correlate with gland functionality. Here we compare several models of parotid gland subregional relative importance with PSMA positron emission tomography (PET) uptake. We then develop a predictive model for Clarket al's relative importance estimates using PSMA PET and CT radiomic features, and demonstrate a methodology for predicting patient-specific importance deviations from the population.Approach. Intra-parotid gland uptake was compared with four regional importance models using 30 [18F]DCFPyL PSMA PET images. The correlation of uptake and importance was ascertained when numerous non-overlapping subregions were defined, while a paired t-test was used to compare binary region pairs. A radiomics-based predictive model of population importance was developed using a double cross-validation methodology. A model was then devised for supplementing population-level subregional importance estimates for each patient using patient-specific radiomic features.Main Results. Anticorrelative relationships were found to exist between PSMA PET uptake and four independent models of subregional parotid gland importance from the literature. Kernel Ridge Regression with principal component analysis feature selection performed best over test sets (Mean Absolute Error = 0.08), with gray level co-occurrence matrix (GLCM) features being particularly important. Deblurring PSMA PET images with neural blind deconvolution strengthened correlations and improved model performance.Significance. This study suggests that regions of relatively low PSMA PET uptake in parotid glands may exhibit relatively high dose-sensitivity. We've demonstrated the utility of PSMA PET radiomic features for predicting relative importance within subregions of parotid glands. PSMA PET appears to be a promising quantitative imaging modality for analyzing salivary gland functionality.}, } @article {pmid38270797, year = {2024}, author = {Singh, S and Borkar, MR and Bhatt, LK}, title = {Transposable Elements: Emerging Therapeutic Targets in Neurodegenerative Diseases.}, journal = {Neurotoxicity research}, volume = {42}, number = {1}, pages = {9}, pmid = {38270797}, issn = {1476-3524}, mesh = {Humans ; *Neurodegenerative Diseases/genetics ; DNA Transposable Elements/genetics ; *Amyotrophic Lateral Sclerosis ; *Alzheimer Disease ; *Parkinson Disease ; }, abstract = {Neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS), are characterized by the progressive loss of neuronal function and structure. While several genetic and environmental factors have been implicated in the pathogenesis of these disorders, emerging evidence suggests that transposable elements (TEs), once considered "junk DNA," play a significant role in their development and progression. TEs are mobile genetic elements capable of moving within the genome, and their dysregulation has been associated with genomic instability, altered gene expression, and neuroinflammation. This review provides an overview of TEs, including long interspersed nuclear elements (LINEs), short interspersed nuclear elements (SINEs), and endogenous retroviruses (ERVs), mechanisms of repression and derepression, and their potential impact on neurodegeneration. The evidence linking TEs to AD, PD, and ALS by shedding light on the complex interactions between TEs and neurodegeneration has been discussed. Furthermore, the therapeutic potential of targeting TEs in neurodegenerative diseases has been explored. Understanding the role of TEs in neurodegeneration holds promise for developing novel therapeutic strategies aimed at mitigating disease progression and preserving neuronal health.}, } @article {pmid38270730, year = {2024}, author = {Abbasi, A and Fryk, H and Rudnik, J and White, R and Vanderkelen, M and Scowcroft, A and Bonar, K}, title = {Using an expanded algorithm to estimate prevalence of amyotrophic lateral sclerosis in U.S. and UK.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {45}, number = {5}, pages = {2321-2324}, pmid = {38270730}, issn = {1590-3478}, mesh = {Humans ; Riluzole/therapeutic use ; *Amyotrophic Lateral Sclerosis/diagnosis ; Prevalence ; *Motor Neuron Disease ; Algorithms ; United Kingdom/epidemiology ; }, abstract = {BACKGROUND: There is an increasing need to better understand the burden of amyotrophic lateral sclerosis (ALS) using real-world data (RWD). However, identifying ALS cases using RWD presents several challenges due to the rarity of ALS and the differences in database coding systems.

METHODS: MarketScan claims, and the UK Clinical Practice Research Datalink (CPRD) databases were searched for diagnosis codes of ALS or MND, the only drugs approved for treating ALS (riluzole and edaravone) and clinical visits with 12-month enrolment prior to 1 January 2011. The main algorithm required ≥ 1 ALS diagnosis code together with prescriptions or clinical visits. We expanded the existing algorithm to identify unspecific (possible) ALS group that had codes for motor neuron disease (MND) and the ALS drugs. The study period was from 1 January 2011 until 31 December 2020.

RESULTS: We identified 16,246 patients with ≥ 1 ALS code in Marketscan (denominator n = 85,279,619), yet only 184 were found in the UK CPRD (denominator n = 21,318,589). Using the main algorithm 9,433 ALS patients were included in MarketScan, with a prevalence ranged between 4.5 per 100,000 in 2019 and 6.2 in 2015. In MarketScan, 3,658 (4.3 per 100,000) had ≥ 1 MND code and the ALS drug codes (possible cases). In CPRD, 47.9% of 2,785 patients with ≥ 1 MND code had a prescription for riluzole (6.3 per 100,000), regarded as possible ALS cases.

CONCLUSIONS: The expanded algorithm enabled the identification of a large population with ALS, or possible ALS, and the estimation of ALS prevalence in MarketScan and CPRD.}, } @article {pmid38270442, year = {2024}, author = {Smith, R and Hovren, H and Bowser, R and Bakkar, N and Garruto, R and Ludolph, A and Ravits, J and Gaertner, L and Murphy, D and Lebovitz, R}, title = {Misfolded alpha-synuclein in amyotrophic lateral sclerosis: Implications for diagnosis and treatment.}, journal = {European journal of neurology}, volume = {31}, number = {4}, pages = {e16206}, pmid = {38270442}, issn = {1468-1331}, mesh = {Humans ; *alpha-Synuclein/metabolism ; *Amyotrophic Lateral Sclerosis/pathology ; Lewy Bodies/metabolism/pathology ; Superoxide Dismutase-1 ; }, abstract = {BACKGROUND: Alpha-synuclein (α-Syn) oligomers and fibrils have been shown to augment the aggregation of TAR DNA-binding Protein 43 (TDP-43) monomers in vitro, supporting the idea that TDP-43 proteinopathies such as ALS may be modulated by the presence of toxic forms of α-Syn. Recently, parkinsonian features were reported in a study of European patients and Lewy bodies have been demonstrated pathologically in a similar series of patients. Based on these and other considerations, we sought to determine whether seed-competent α-Syn can be identified in spinal fluid of patients with ALS including familial, sporadic, and Guamanian forms of the disease.

METHODS: Based on the finding that α-Syn has been found to be a prion-like protein, we have utilized a validated α-Synuclein seed amplification assay to determine if seed-competent α-Syn could be detected in the spinal fluid of patients with ALS.

RESULTS: Toxic species of α-Syn were detected in CSF in 18 of 127 ALS patients, 5 of whom were from Guam. Two out of twenty six samples from patients with C9orf72 variant ALS had positive seed-amplification assays (SAAs). No positive tests were noted in superoxide dismutase type 1 ALS subjects (n = 14). The SAA was negative in 31 control subjects.

CONCLUSIONS: Our findings suggest that a sub-group of ALS occurs in which self-replicating α-Syn is detectable and likely contributes to its pathogenesis. This finding may have implications for the diagnosis and treatment of this disorder.}, } @article {pmid38270154, year = {2024}, author = {Jiang, Q and Wei, Q and Zhang, L and Yang, T and Lin, J and Xiao, Y and Li, C and Hou, Y and Ou, R and Liu, K and Zhao, B and Wu, Y and Lai, X and Shang, H}, title = {Peripheral immunity relate to disease progression and prognosis in amyotrophic lateral sclerosis.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {25}, number = {5-6}, pages = {465-474}, doi = {10.1080/21678421.2024.2306969}, pmid = {38270154}, issn = {2167-9223}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/immunology/blood/mortality ; Male ; Female ; Middle Aged ; *Disease Progression ; Aged ; Prognosis ; Adult ; CD4-Positive T-Lymphocytes/immunology ; Immunoglobulin G/blood ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease. Abnormalities in the peripheral immune system in ALS have been paid attention; however, the results of changes in peripheral immune parameters were inconsistent.

METHODS: A total of 1109 ALS patients were enrolled in the study. All patients received clinical evaluation and peripheral immune parameters measurement. The outcomes were analyzed by correlation analysis, multiple linear regression and cox survival analysis.

RESULTS: We found that ALS patients had significantly higher percentage of CD4[+] T cells (39.3 vs. 37.1%, p < 0.001) and CD4[+]/CD8[+] ratio (1.88 vs. 1.72, p = 0.011), significantly lower IgG (11.73 vs.12.82, p < 0.001) and IgA (2130.70 vs. 2284.8, p = 0.013) compared with the health controls. In the multivariate linear model, we found that each increase of 1.262, 0.278, and 4.44E-4 in ALSFRS-R scores were significantly associated with each increment of lymphocyte count, IgG, and IgA, respectively. However, each decrease of 0.341, 0.068, and 0.682 in ALSFRS-R score was associated with each increment in neutrophils, CD4[+] T cells, and CD4[+]/CD8[+] ratio, respectively. Cox survival regression analysis showed that the death risk of ALS patients was related to the levels of C3 (HR 0.592, 95% CI 0.361-0.973).

CONCLUSION: We found that there were differences in peripheral immune parameters of ALS patients with the severity of the disease, especially neutrophil, lymphocyte, CD4[+] T, and IgG; C3 is an independent predictor of survival in ALS patients. More studies are needed to elucidate the mechanisms associated with altered immune parameters in ALS.}, } @article {pmid38268041, year = {2024}, author = {Cascella, M and Monaco, F and Vittori, A and Elshazly, M and Carlucci, A and Piazza, O}, title = {Bridging knowledge gaps: a bibliometric analysis of non-invasive ventilation in palliative care studies.}, journal = {Journal of anesthesia, analgesia and critical care}, volume = {4}, number = {1}, pages = {5}, pmid = {38268041}, issn = {2731-3786}, abstract = {BACKGROUND: Despite being a useful strategy for providing respiratory support to patients with advanced or terminal illnesses, non-invasive ventilation (NIV) requires in-depth investigation in several key aspects.

OBJECTIVES: This bibliometric analysis seeks to comprehensively examine the existing research on the subject. Its goal is to uncover valuable insights that can inform the prediction trajectory of studies, guide the implementation of corrective measures, and contribute to the improvement of research networks.

METHODS: A comprehensive review of literature on NIV in the context of palliative care was conducted using the Web of Science core collection online database. The search utilized the key terms "non-invasive ventilation" and "palliative care" to identify the most relevant articles. All data were gathered on November 7, 2023. Relevant information from documents meeting the specified criteria was extracted, and Journal Citation Reports™ 2022 (Clarivate Analytics) served as the data source. The analysis employed literature analysis and knowledge visualization tools, specifically CiteScope (version 6.2.R4) and VOSviewer (version 1.6.20).

RESULTS: A dataset with bibliometric findings from 192 items was analyzed. We found a consistent upward of the scientific output trend over time. Guidelines on amyotrophic lateral sclerosis management received the highest number of citations. Most documents were published in top-ranked journals. Less than one-third of the documents pertain to clinical studies, especially retrospective analyses (25%). Key topics such as "decision making", and "communication" were less addressed.

CONCLUSIONS: Given the substantial clinical implications, further high-quality studies on this subject are recommended. Encouraging international collaborations is needed. Despite the growing volume of documents in the field, this bibliometric analysis indicates a decline in collaborative networks.}, } @article {pmid38267984, year = {2024}, author = {Irwin, KE and Sheth, U and Wong, PC and Gendron, TF}, title = {Fluid biomarkers for amyotrophic lateral sclerosis: a review.}, journal = {Molecular neurodegeneration}, volume = {19}, number = {1}, pages = {9}, pmid = {38267984}, issn = {1750-1326}, support = {R01 NS095969/NS/NINDS NIH HHS/United States ; T32 GM136577/GM/NIGMS NIH HHS/United States ; P01NS084974/NH/NIH HHS/United States ; U19AG063911/NH/NIH HHS/United States ; RF1 NS095969/NS/NINDS NIH HHS/United States ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis ; *Neurodegenerative Diseases ; Biomarkers ; Motor Neurons ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the loss of upper and lower motor neurons. Presently, three FDA-approved drugs are available to help slow functional decline for patients with ALS, but no cure yet exists. With an average life expectancy of only two to five years after diagnosis, there is a clear need for biomarkers to improve the care of patients with ALS and to expedite ALS treatment development. Here, we provide a review of the efforts made towards identifying diagnostic, prognostic, susceptibility/risk, and response fluid biomarkers with the intent to facilitate a more rapid and accurate ALS diagnosis, to better predict prognosis, to improve clinical trial design, and to inform interpretation of clinical trial results. Over the course of 20 + years, several promising fluid biomarker candidates for ALS have emerged. These will be discussed, as will the exciting new strategies being explored for ALS biomarker discovery and development.}, } @article {pmid38267577, year = {2024}, author = {Obara, CJ and Nixon-Abell, J and Moore, AS and Riccio, F and Hoffman, DP and Shtengel, G and Xu, CS and Schaefer, K and Pasolli, HA and Masson, JB and Hess, HF and Calderon, CP and Blackstone, C and Lippincott-Schwartz, J}, title = {Motion of VAPB molecules reveals ER-mitochondria contact site subdomains.}, journal = {Nature}, volume = {626}, number = {7997}, pages = {169-176}, pmid = {38267577}, issn = {1476-4687}, mesh = {Humans ; Amyotrophic Lateral Sclerosis/genetics ; *Endoplasmic Reticulum/chemistry/metabolism/ultrastructure ; *Mitochondria/chemistry/metabolism/ultrastructure ; *Mitochondrial Membranes/chemistry/metabolism/ultrastructure ; Signal Transduction ; *Vesicular Transport Proteins/genetics/metabolism/ultrastructure ; Microscopy, Electron ; Imaging, Three-Dimensional ; Binding Sites ; Diffusion ; Time Factors ; Mutation ; Homeostasis ; *Movement ; }, abstract = {To coordinate cellular physiology, eukaryotic cells rely on the rapid exchange of molecules at specialized organelle-organelle contact sites[1,2]. Endoplasmic reticulum-mitochondrial contact sites (ERMCSs) are particularly vital communication hubs, playing key roles in the exchange of signalling molecules, lipids and metabolites[3,4]. ERMCSs are maintained by interactions between complementary tethering molecules on the surface of each organelle[5,6]. However, due to the extreme sensitivity of these membrane interfaces to experimental perturbation[7,8], a clear understanding of their nanoscale organization and regulation is still lacking. Here we combine three-dimensional electron microscopy with high-speed molecular tracking of a model organelle tether, Vesicle-associated membrane protein (VAMP)-associated protein B (VAPB), to map the structure and diffusion landscape of ERMCSs. We uncovered dynamic subdomains within VAPB contact sites that correlate with ER membrane curvature and undergo rapid remodelling. We show that VAPB molecules enter and leave ERMCSs within seconds, despite the contact site itself remaining stable over much longer time scales. This metastability allows ERMCSs to remodel with changes in the physiological environment to accommodate metabolic needs of the cell. An amyotrophic lateral sclerosis-associated mutation in VAPB perturbs these subdomains, likely impairing their remodelling capacity and resulting in impaired interorganelle communication. These results establish high-speed single-molecule imaging as a new tool for mapping the structure of contact site interfaces and reveal that the diffusion landscape of VAPB at contact sites is a crucial component of ERMCS homeostasis.}, } @article {pmid38267456, year = {2024}, author = {Feró, O and Varga, D and Nagy, É and Karányi, Z and Sipos, É and Engelhardt, J and Török, N and Balogh, I and Vető, B and Likó, I and Fóthi, Á and Szabó, Z and Halmos, G and Vécsei, L and Arányi, T and Székvölgyi, L}, title = {DNA methylome, R-loop and clinical exome profiling of patients with sporadic amyotrophic lateral sclerosis.}, journal = {Scientific data}, volume = {11}, number = {1}, pages = {123}, pmid = {38267456}, issn = {2052-4463}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics ; DNA ; Epigenome ; Exome ; R-Loop Structures ; *DNA Methylation ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by the death of motor neurons, the aetiology of which is essentially unknown. Here, we present an integrative epigenomic study in blood samples from seven clinically characterised sporadic ALS patients to elucidate molecular factors associated with the disease. We used clinical exome sequencing (CES) to study DNA variants, DNA-RNA hybrid immunoprecipitation sequencing (DRIP-seq) to assess R-loop distribution, and reduced representation bisulfite sequencing (RRBS) to examine DNA methylation changes. The above datasets were combined to create a comprehensive repository of genetic and epigenetic changes associated with the ALS cases studied. This repository is well-suited to unveil new correlations within individual patients and across the entire patient cohort. The molecular attributes described here are expected to guide further mechanistic studies on ALS, shedding light on the underlying genetic causes and facilitating the development of new epigenetic therapies to combat this life-threatening disease.}, } @article {pmid38267282, year = {2024}, author = {Tortorella, MEC and Alves, I and Gromicho, M and Santos, MO and de Carvalho, M}, title = {Proton pump inhibitors and amyotrophic lateral sclerosis: A case-control study.}, journal = {Journal of the neurological sciences}, volume = {457}, number = {}, pages = {122895}, doi = {10.1016/j.jns.2024.122895}, pmid = {38267282}, issn = {1878-5883}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy ; Case-Control Studies ; Proton Pump Inhibitors/adverse effects ; Disease Progression ; }, } @article {pmid38267040, year = {2024}, author = {Fukui, Y and Shirakawa, H and Kaneko, S and Nagayasu, K}, title = {Wild-Type DCTN1 Suppresses the Aggregation of DCTN1 Mutants Associated with Perry Disease.}, journal = {Biological & pharmaceutical bulletin}, volume = {47}, number = {1}, pages = {253-258}, doi = {10.1248/bpb.b23-00828}, pmid = {38267040}, issn = {1347-5215}, mesh = {Humans ; Dynactin Complex/genetics ; HEK293 Cells ; Cytosol ; Mutation ; *Motor Neuron Disease ; }, abstract = {Perry disease, a rare autosomal dominant neurodegenerative disorder, is characterized by parkinsonism, depression or apathy, unexpected weight loss, and central hypoventilation. Genetic analyses have revealed a strong association between point mutations in the dynactin I gene (DCTN1) coding p150[glued] and Perry disease. Although previous reports have suggested a critical role of p150[glued] aggregation in Perry disease pathology, whether and how p150[glued] mutations affect protein aggregation is not fully understood. In this study, we comprehensively investigated the intracellular distribution of the p150[glued] mutants in HEK293T cells. We further assessed the effect of co-overexpression of the wild-type p150[glued] protein with mutants on the formation of mutant aggregates. Notably, overexpression of p150[glued] mutants identified in healthy controls, which is also associated with amyotrophic lateral sclerosis, showed a thread-like cytoplasmic distribution, similar to the wild-type p150[glued]. In contrast, p150[glued] mutants in Perry disease and motor neuron disease caused aggregation. In addition, the co-overexpression of the wild-type protein with p150[glued] mutants in Perry disease suppressed aggregate formation. In contrast, the p150[glued] aggregation of motor neuron disease mutants was less affected by the wild-type p150[glued]. Further investigation of the mechanism of aggregate formation, contents of the aggregates, and biological mechanisms of Perry disease could help develop novel therapeutics.}, } @article {pmid38266764, year = {2024}, author = {Lundt, S and Zhang, N and Polo-Parada, L and Wang, X and Ding, S}, title = {Dietary NMN supplementation enhances motor and NMJ function in ALS.}, journal = {Experimental neurology}, volume = {374}, number = {}, pages = {114698}, doi = {10.1016/j.expneurol.2024.114698}, pmid = {38266764}, issn = {1090-2430}, support = {R01 NS069726/NS/NINDS NIH HHS/United States ; R01 NS094539/NS/NINDS NIH HHS/United States ; R01 NS123023/NS/NINDS NIH HHS/United States ; }, mesh = {Humans ; Mice ; Animals ; *Amyotrophic Lateral Sclerosis/metabolism ; *Neurodegenerative Diseases/metabolism ; NAD/metabolism ; Neuromuscular Junction/metabolism ; Dietary Supplements ; Mice, Transgenic ; Disease Models, Animal ; Superoxide Dismutase-1/genetics/metabolism ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disease that causes the degeneration of motor neurons in the motor cortex and spinal cord. Patients with ALS experience muscle weakness and atrophy in the limbs which eventually leads to paralysis and death. NAD[+] is critical for energy metabolism, such as glycolysis and oxidative phosphorylation, but is also involved in non-metabolic cellular reactions. In the current study, we determined whether the supplementation of nicotinamide mononucleotide (NMN), an NAD[+] precursor, in the diet had beneficial impacts on disease progression using a SOD1[G93A] mouse model of ALS. We found that the ALS mice fed with an NMN-supplemented diet (ALS[+NMN] mice) had modestly extended lifespan and exhibited delayed motor dysfunction. Using electrophysiology, we studied the effect of NMN on synaptic transmission at neuromuscular junctions (NMJs) in symptomatic of ALS mice (18 weeks old). ALS[+NMN] mice had larger end-plate potential (EPP) amplitudes and maintained better responses than ALS mice, and also had restored EPP facilitation. While quantal content was not affected by NMN, miniature EPP (mEPP) amplitude and frequency were elevated in ALS[+NMN] mice. NMN supplementation in diet also improved NMJ morphology, innervation, mitochondrial structure, and reduced reactive astrogliosis in the ventral horn of the lumbar spinal cord. Overall, our results indicate that dietary consumption of NMN can slow motor impairment, enhance NMJ function and improve healthspan of ALS mice.}, } @article {pmid38266701, year = {2024}, author = {Eisen, A and Nedergaard, M and Gray, E and Kiernan, MC}, title = {The glymphatic system and Amyotrophic lateral sclerosis.}, journal = {Progress in neurobiology}, volume = {234}, number = {}, pages = {102571}, doi = {10.1016/j.pneurobio.2024.102571}, pmid = {38266701}, issn = {1873-5118}, mesh = {Humans ; *Glymphatic System/metabolism/pathology ; *Amyotrophic Lateral Sclerosis/metabolism ; Brain/metabolism ; *Alzheimer Disease/metabolism ; Sleep ; }, abstract = {The glymphatic system and the meningeal lymphatic vessels provide a pathway for transport of solutes and clearance of toxic material from the brain. Of specific relevance to ALS, this is applicable for TDP-43 and glutamate, both major elements in disease pathogenesis. Flow is propelled by arterial pulsation, respiration, posture, as well as the positioning and proportion of aquaporin-4 channels (AQP4). Non-REM slow wave sleep is the is key to glymphatic drainage which discontinues during wakefulness. In Parkinson's disease and Alzheimer's disease, sleep impairment is known to predate the development of characteristic clinical features by several years and is associated with progressive accumulation of toxic proteinaceous products. While sleep issues are well described in ALS, consideration of preclinical sleep impairment or the potential of a failing glymphatic system in ALS has rarely been considered. Here we review how the glymphatic system may impact ALS. Preclinical sleep impairment as an unrecognized major risk factor for ALS is considered, while potential therapeutic options to improve glymphatic flow are explored.}, } @article {pmid38265475, year = {2024}, author = {Xiang, Y and Song, X and Long, D}, title = {Ferroptosis regulation through Nrf2 and implications for neurodegenerative diseases.}, journal = {Archives of toxicology}, volume = {98}, number = {3}, pages = {579-615}, pmid = {38265475}, issn = {1432-0738}, support = {81673227//National Natural Science Foundation of China/ ; 2020JJ4080//Natural Science Foundation of Hunan Province/ ; }, mesh = {Humans ; *Neurodegenerative Diseases ; NF-E2-Related Factor 2/metabolism ; *Ferroptosis ; Oxidative Stress/physiology ; Antioxidants/metabolism ; }, abstract = {This article provides an overview of the background knowledge of ferroptosis in the nervous system, as well as the key role of nuclear factor E2-related factor 2 (Nrf2) in regulating ferroptosis. The article takes Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS) as the starting point to explore the close association between Nrf2 and ferroptosis, which is of clear and significant importance for understanding the mechanism of neurodegenerative diseases (NDs) based on oxidative stress (OS). Accumulating evidence links ferroptosis to the pathogenesis of NDs. As the disease progresses, damage to the antioxidant system, excessive OS, and altered Nrf2 expression levels, especially the inhibition of ferroptosis by lipid peroxidation inhibitors and adaptive enhancement of Nrf2 signaling, demonstrate the potential clinical significance of Nrf2 in detecting and identifying ferroptosis, as well as targeted therapy for neuronal loss and mitochondrial dysfunction. These findings provide new insights and possibilities for the treatment and prevention of NDs.}, } @article {pmid38264389, year = {2023}, author = {Gouveia, C and Araújo, L and Freitas, S and Correia, J and Passos, V and Camacho, G and Gomes, L and Fragoeiro, H and Camacho, C and Chambino, B}, title = {A Palliative Care Approach to Amyotrophic Lateral Sclerosis.}, journal = {Cureus}, volume = {15}, number = {12}, pages = {e51048}, pmid = {38264389}, issn = {2168-8184}, abstract = {INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a degenerative disease characterized by motor dysfunction. Currently, treatment options are limited and management is based mostly on symptom control and quality of life optimization, so palliative care plays a fundamental role. Our objective was to characterize the ALS population in Madeira Island that was referenced and/or followed by a palliative care unit over a five-year period.

METHODS: Longitudinal, retrospective, descriptive, and observational study to analyze patients with ALS who were referred and/or followed by a palliative care unit during a five-year period, between 2017 and 2021. Patient's medical electronic and physical records were analyzed to gather data. Descriptive and inferential statistical analysis was done using Microsoft Excel and Statistical Package for the Social Sciences (version 28.0.1).

RESULTS: During this five-year period, a total of 38 patients were diagnosed with ALS in Madeira Island and 23 (60.53%) were referred to palliative care. Three patients died before assessment, so 20 (50.63%) were followed by the palliative care team. They had a median life expectancy of 425 days and the median time spent in palliative care was 137 days. Of this population, 56.52% (n=13) was male with an average age of 64 years. The median period from diagnosis to referral was 167 days, with most referrals being made by family medicine (39.13%; n=9) motivated by uncontrolled symptoms (95.65%; n=22). The median period from referral to first assessment by a palliative care physician was 19 days. The Palliative Performance Scale (PPS) and Confusion Assessment Method (CAM) applied on the first visit had a median score of 40% in the former and was negative in 95.00% (n=19) of patients in the latter. Advanced care directives were present in 55.00% (n=11) of patients and all provided care was in accordance with the patient's wishes. The most common symptoms were dysphagia, dyspnea, pain, anxiety, and sialorrhea. The most used drugs were morphine, riluzole, butylscopolamine, bisacodyl, and midazolam. As for other interventions, 55.00% (n=11) of patients underwent noninvasive ventilation (NIV), 15.00% (n=3) were submitted to percutaneous endoscopic gastrostomy (PEG), and one patient (5.00%) was nasogastrically intubated. The death rate was 95.00% (n=19) with 73.68% (n=14) of deaths occurring in the palliative care unit.

CONCLUSION: Literature has shown that there are many advantages to the early inclusion of palliative care in ALS management, achieving effective symptom control and greater quality of life, but also reducing caregiver burden. However, in this study, we found that referrals to palliative care were late and included mostly cases of advanced disease with uncontrolled symptoms.}, } @article {pmid38263228, year = {2024}, author = {Ayyappan, MV and Kishore, P and Panda, SK and Kumar, A and Uchoi, D and Nadella, RK and Priyadarshi, H and Obaiah, MC and George, D and Hamza, M and Ramannathan, SK and Ravishankar, CN}, title = {Emergence of multidrug resistant, ctx negative seventh pandemic Vibrio cholerae O1 El Tor sequence type (ST) 69 in coastal water of Kerala, India.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {2031}, pmid = {38263228}, issn = {2045-2322}, mesh = {Animals ; *Vibrio cholerae O1 ; Ecosystem ; Pandemics ; Phylogeny ; *Cholera ; India ; *Lepidoptera ; Water ; }, abstract = {Seventh pandemic Vibrio choleare O1 El Tor strain is responsible for the on-going pandemic outbreak of cholera globally. This strain evolved from non-pathogenic V. cholerae by acquiring seventh pandemic gene (VC 2346), pandemic Islands (VSP1 and VSP2), pathogenicity islands (VP1 and VP2) and CTX prophage region. The cholera toxin production is mainly attributed to the presence of ctx gene in these strains. However, several variants of this strain emerged as hybrid strains or atypical strains. The present study aimed to assess the aquatic environment of Cochin, India, over a period of 5 years for the emergence of multidrug resistant V. cholerae and its similarity with seventh pandemic strain. The continuous surveillance and monitoring resulted in the isolation of ctx negative, O1 positive V. cholerae isolate (VC6) from coastal water, Cochin, Kerala. The isolate possessed the biotype specific O1 El Tor tcpA gene and lacked other biotype specific ctx, zot, ace and rst genes. Whole genome analysis revealed the isolate belongs to pandemic sequence type (ST) 69 with the possession of pandemic VC2346 gene, pathogenic island VPI1, VPI2, and pandemic island VSP1 and VSP2. The isolate possessed several insertion sequences and the SXT/R391 family related Integrative Conjugative Elements (ICEs). In addition to this, the isolate genome carried virulence genes such as VgrG, mshA, ompT, toxR, ompU, rtxA, als, VasX, makA, and hlyA and antimicrobial resistance genes such as gyrA, dfrA1, strB, parE, sul2, parC, strA, VC1786ICE9-floR, and catB9. Moreover, the phylogenetic analysis suggests that the isolate genome is more closely related to seventh pandemic V. cholerae O1 N16961 strain. This study reports the first incidence of environmental ctx negative seventh pandemic V. choleare O1 El Tor isolate, globally and its presence in the aquatic system likely to induce toxicity in terms of public health point of view. The presence of this isolate in the aquatic environment warns the strict implementation of the epidemiological surveillance on the occurrence of emerging strains and the execution of flagship program for the judicious use of antibiotics in the aquatic ecosystem.}, } @article {pmid38262892, year = {2024}, author = {Adams-Mitchell, CJ and Smith, WR and Wilkie, DJ}, title = {Dysphagia in patients with sickle cell disease: An understudied problem.}, journal = {Journal of the National Medical Association}, volume = {116}, number = {2 Pt 1}, pages = {126-130}, doi = {10.1016/j.jnma.2023.11.005}, pmid = {38262892}, issn = {1943-4693}, mesh = {Humans ; *Deglutition Disorders/complications/diagnosis ; *Anemia, Sickle Cell/complications ; *Stroke/complications ; *Nervous System Diseases/complications ; *Parkinson Disease ; }, abstract = {Dysphagia which is defined as disordered swallowing is well known as one of the most common and dangerous symptoms of many diseases, including neurological disorders such as Parkinson's disease, amyotrophic lateral sclerosis, myasthenia gravis, and most commonly, stroke. Strokes are a potentially devastating complication of sickle cell disease (SCD), the most common genetic hemoglobinopathy worldwide, yet little is known about dysphagia as it relates to SCD. Thus, the purposes of this article are to review briefly the primary causes and health consequences of dysphagia, to highlight the relevance of dysphagia to SCD, to review what little is known about dysphagia in SCD, to recommend, based on our consensus and the available literature, when to screen, evaluate, and monitor dysphagia in patients with SCD, and to outline unanswered questions where research on dysphagia in SCD might improve health outcomes.}, } @article {pmid38262101, year = {2024}, author = {Masegosa, VM and Navarro, X and Herrando-Grabulosa, M}, title = {ICA-27243 improves neuromuscular function and preserves motoneurons in the transgenic SOD1[G93A] mice.}, journal = {Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics}, volume = {21}, number = {2}, pages = {e00319}, pmid = {38262101}, issn = {1878-7479}, mesh = {Mice ; Animals ; Mice, Transgenic ; *Amyotrophic Lateral Sclerosis/drug therapy/genetics ; Superoxide Dismutase-1/genetics ; *Neurodegenerative Diseases ; Motor Neurons ; Spinal Cord ; Disease Models, Animal ; Superoxide Dismutase ; *Benzamides ; *Pyridines ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by the death of upper and lower motor neurons (MNs). Excessive neuronal excitability has been implicated in MN degeneration; thus, modulation of hyperexcitability appears as a promising therapeutic strategy. Potassium channels are attractive targets since they can be activated at subthreshold voltages and can regulate neuronal excitability. In this study, we assayed the effects of N-(6-Chloro-pyridin-3-yl)-3,4-difluorobenzamide compound, known as ICA-27243, as a potential treatment for ALS. ICA-27243 is a highly selective Kv7.2/7.3 opener used mainly in epilepsy models. In the in vitro model of spinal cord organotypic cultures (SCOCs) exposed to acute excitotoxicity, ICA-27243 prevented MN degeneration at a dose-of 10 μM. Administration of ICA-27243 to transgenic SOD1[G93A] ALS mice improved the decline of neuromuscular function, maintained locomotion and coordination in the rotarod, decreased spinal MN death and attenuated glial reactivity. In conclusion, we report here for the first time that ICA-27243 is an effective treatment for ALS, emphasizing the potential of targeting Kv channels to reduce neuronal hyperexcitability.}, } @article {pmid38261982, year = {2024}, author = {Moglia, C and Calvo, A and Canosa, A and Manera, U and Vasta, R and Di Pede, F and Daviddi, M and Matteoni, E and Brunetti, M and Sbaiz, L and Cabras, S and Gallone, S and Grassano, M and Peotta, L and Palumbo, F and Mora, G and Iazzolino, B and Chio, A}, title = {Cognitive and Behavioral Features of Patients With Amyotrophic Lateral Sclerosis Who Are Carriers of the TARDBP Pathogenic Variant.}, journal = {Neurology}, volume = {102}, number = {4}, pages = {e208082}, pmid = {38261982}, issn = {1526-632X}, mesh = {Aged ; Female ; Humans ; Middle Aged ; *Amyotrophic Lateral Sclerosis ; *Apathy ; Cognition ; *Frontotemporal Dementia ; Memory, Short-Term ; Male ; }, abstract = {BACKGROUND AND OBJECTIVES: TARDBP patients are considered particularly prone to cognitive involvement, but no systematic studies of cognitive impairment in TARDBP patients are available. The aim of this article was to depict in depth the cognitive-behavioral characteristics of a cohort of patients with amyotrophic lateral sclerosis (ALS) carrying TARDBP pathogenetic variants followed by an ALS referral center.

METHODS: We enrolled all patients with ALS seen at the Turin ALS expert center in the 2009-2021 period who underwent extensive genetic testing and a neuropsychological battery encompassing executive function, verbal memory, language, visual memory, visuoconstructive abilities, attention/working memory, psychomotor speed, nonverbal intelligence, cognitive flexibility, social cognition, and behavior. Tests were compared with the Mann-Whitney U test on age-corrected, sex-corrected, and education-corrected scores. Cognition was classified as normal (ALS-CN); isolated cognitive impairment (ALSci), that is, evidence of executive and/or language dysfunction; isolated behavioral impairment (ALSbi), that is, identification of apathy; cognitive and behavioral impairment (ALScbi), that is, evidence meeting the criteria for both ALSci and ALSbi; and frontotemporal dementia (ALS-FTD).

RESULTS: This study includes 33 patients with TARDBP pathogenetic variants (TARDBP-ALS) (median age 61 years [interquartile range (IQR) 53-67], 8 female [24.2%]) and 928 patients with ALS not carrying the pathogenic variant (WT-ALS) (median age 67 years [IQR 59-74], 386 female [41.6%]). TARDBP-ALS cases were also compared with 129 matched controls (median age 66 years [IQR 57.5-71.5], 55 female [42.6%]). TARDBP-ALS and WT-ALS patients were cognitively classified as ALS-CN (54% vs 58.8%, respectively), ALSci (21.2% vs 18.3%), ALSci (9.1% vs 9.5%), ALScbi (6.1% vs 6.0%), and ALS-FTD (9.1 vs 6.7%), with no significant difference (p = 0.623). Compared with controls, TARDBP-ALS had a worse performance in executive functions, visual memory, visuoconstructive abilities, verbal fluency, and the apathy behavioral component of FrSBe. The scores of performed tests, including all Edinburgh Cognitive and Behavioral ALS Screen subdomains, were similar in TARDBP-ALS and WT-ALS.

DISCUSSION: TARDBP-ALS patients were significantly more impaired than controls in most examined domains but do not show any specific pattern of cognitive impairment compared with WT-ALS. Our findings are relevant both clinically, considering the effect of cognitive impairment on patients' decision-making and caregivers' burden, and in designing clinical trials for the treatment of patients carrying TARDBP pathogenetic variants.}, } @article {pmid38261942, year = {2024}, author = {Sumera, K and Ilczak, T and Bakkerud, M and Lane, JD and Pallas, J and Martorell, SO and Sumera, A and Webster, CA and Quinn, T and Sandars, J and Niroshan Siriwardena, A}, title = {CPR Quality Officer role to improve CPR quality: A multi-centred international simulation randomised control trial.}, journal = {Resuscitation plus}, volume = {17}, number = {}, pages = {100537}, pmid = {38261942}, issn = {2666-5204}, abstract = {BACKGROUND: An out-of-hospital cardiac arrest requires early recognition, prompt and quality clinical interventions, and coordination between different clinicians to improve outcomes. Clinical team leaders and clinical teams have high levels of cognitive burden. We aimed to investigate the effect of a dedicated Cardio-Pulmonary Resuscitation (CPR) Quality Officer role on team performance.

METHODS: This multi-centre randomised control trial used simulation in universities from the UK, Poland, and Norway. Student Paramedics participated in out-of-hospital cardiac arrest scenarios before randomisation to either traditional roles or assigning one member as the CPR Quality Officer. The quality of CPR was measured using QCPR® and Advanced Life Support (ALS) elements were evaluated.

RESULTS: In total, 36 teams (108 individuals) participated. CPR quality from the first attempt (72.45%, 95% confidence interval [CI] 64.94 to 79.97) significantly increased after addition of the CPR Quality role (81.14%, 95% CI 74.20 to 88.07, p = 0.045). Improvement was not seen in the control group. The time to first defibrillation had no significant difference in the intervention group between the first attempt (53.77, 95% CI 36.57-70.98) and the second attempt (48.68, 95% CI 31.31-66.05, p = 0.84). The time to manage an obstructive airway in the intervention group showed significant difference (p = 0.006) in the first attempt (168.95, 95% CI 110.54-227.37) compared with the second attempt (136.95, 95% CI 87.03-186.88, p = 0.1).

CONCLUSION: A dedicated CPR Quality Officer in simulated scenarios improved the quality of CPR compressions without a negative impact on time to first defibrillation, managing the airway, or adherence to local ALS protocols.}, } @article {pmid38261358, year = {2024}, author = {}, title = {Correction to: Persistence of Kii amyotrophic lateral sclerosis after the 2000s and its characteristic aging-related tau astrogliopathy.}, journal = {Journal of neuropathology and experimental neurology}, volume = {83}, number = {9}, pages = {795}, doi = {10.1093/jnen/nlae006}, pmid = {38261358}, issn = {1554-6578}, } @article {pmid38261295, year = {2024}, author = {Khabibrakhmanov, AN and Zueva, IV and Petrov, KA and Bogdanov, EI and Mukhamedyarov, MA}, title = {[Plasma and salivary acetylcholinesterase activity in amyotrophic lateral sclerosis].}, journal = {Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova}, volume = {124}, number = {1}, pages = {128-134}, doi = {10.17116/jnevro2024124011128}, pmid = {38261295}, issn = {1997-7298}, mesh = {Animals ; Humans ; Mice ; Middle Aged ; *Acetylcholinesterase ; *Amyotrophic Lateral Sclerosis/diagnosis ; Mice, Transgenic ; Saliva ; }, abstract = {OBJECTIVE: Assessment of plasma and salivary acetylcholinesterase (AChE) activity in patients with amyotrophic lateral sclerosis (ALS) and in an animal model of the disease.

MATERIAL AND METHODS: We studied 41 participants, aged 31 to 71 years, including 17 patients with diagnosed ALS (ALS group, average age 62.3±2.2), 9 patients with ALS mimics (disease control, average age 58.1±2.9), and 15 healthy people (normal control, average age 57.7±2.3). Plasma and salivary AChE activity was measured by using the Ellman colorimetric method. ALS severity was assessed using the ALSFRS-R scale. The King's College staging system and the Milano-Torino Scale (MiToS) were used to determine the stage of the disease. Transgenic FUS-mice were used as ALS model.

RESULTS: Plasma AChE activity in the ALS group did not significantly differ from the control groups. There was also no significant correlation between plasma AChE activity and disease parameters such as the stage, duration, rate of progression, and severity. In transgenic FUS-mice plasma AChE activity also did not differ from wild-type mice. However, it has been shown that patients with ALS have significantly higher saliva AChE activity compared to normal controls. However, patients with the bulbar form of ALS had significantly higher values of salivary AChE activity compared to healthy controls.

CONCLUSION: In patients with the bulbar form of ALS, an increase in salivary AChE activity was noted, which can be used for diagnostic and prognostic purposes. There is no significant change in plasma AChE activity in ALS patients.}, } @article {pmid38261256, year = {2024}, author = {Ouyang, J and Peng, S and Wu, G and Liu, R}, title = {Association Between Neurodegenerative Diseases and an Increased Risk of Epilepsy Based on Single Nucleotide Polymorphisms: A Mendelian Randomization Study.}, journal = {Molecular neurobiology}, volume = {61}, number = {8}, pages = {5950-5957}, pmid = {38261256}, issn = {1559-1182}, mesh = {Humans ; *Polymorphism, Single Nucleotide/genetics ; *Mendelian Randomization Analysis ; *Epilepsy/genetics ; *Genetic Predisposition to Disease ; *Neurodegenerative Diseases/genetics/epidemiology ; Genome-Wide Association Study ; Risk Factors ; }, abstract = {Epilepsy is a common neurological disorder characterized by transient brain dysfunction, attributed to a multitude of factors. The purpose of this study is to explore whether neurodegenerative diseases, specifically Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS), have a causal effect on epilepsy. Mendelian randomization (MR) methods were used to analyze the causal association between neurodegenerative diseases (AD, PD, ALS, and MS) and epilepsy based on single nucleotide polymorphisms from genome-wide association studies, including inverse-variance weighted, weighted median, MR-Egger, and weighted mode methods. The reliability and stability of the MR analysis results were assessed by the MR-Egger intercept, MR-PRESSO, and heterogeneity tests. Forty-three SNPs were selected for the MR analysis of MS and epilepsy. The inverse-variance weighted method showed a significant causal association between MS and increased risk of epilepsy (odds ratio 1.046; 95% confidence interval 1.001-1.093; P = 0.043). However, AD (P = 0.986), PD (P = 0.894), and ALS (P = 0.533) were not causally associated with epilepsy. Sensitivity analysis showed that the results were robust. The MR study confirmed the causal relationship between genetically predicted MS and epilepsy but did not support the causal relationship between genetically predicted AD, PD, and ALS on epilepsy.}, } @article {pmid38261034, year = {2024}, author = {Sian-Hulsmann, J and Riederer, P}, title = {Virus-induced brain pathology and the neuroinflammation-inflammation continuum: the neurochemists view.}, journal = {Journal of neural transmission (Vienna, Austria : 1996)}, volume = {131}, number = {12}, pages = {1429-1453}, pmid = {38261034}, issn = {1435-1463}, mesh = {Humans ; *Neuroinflammatory Diseases/pathology/immunology/metabolism ; Animals ; Neurodegenerative Diseases/pathology/metabolism/immunology ; Brain/pathology/metabolism/immunology ; Inflammation/pathology/metabolism/immunology ; }, abstract = {Fascinatingly, an abundance of recent studies has subscribed to the importance of cytotoxic immune mechanisms that appear to increase the risk/trigger for many progressive neurodegenerative disorders, including Parkinson's disease (PD), Alzheimer's disease (AD), amyotrophic lateral sclerosis, and multiple sclerosis. Events associated with the neuroinflammatory cascades, such as ageing, immunologic dysfunction, and eventually disruption of the blood-brain barrier and the "cytokine storm", appear to be orchestrated mainly through the activation of microglial cells and communication with the neurons. The inflammatory processes prompt cellular protein dyshomeostasis. Parkinson's and Alzheimer's disease share a common feature marked by characteristic pathological hallmarks of abnormal neuronal protein accumulation. These Lewy bodies contain misfolded α-synuclein aggregates in PD or in the case of AD, they are Aβ deposits and tau-containing neurofibrillary tangles. Subsequently, these abnormal protein aggregates further elicit neurotoxic processes and events which contribute to the onset of neurodegeneration and to its progression including aggravation of neuroinflammation. However, there is a caveat for exclusively linking neuroinflammation with neurodegeneration, since it's highly unlikely that immune dysregulation is the only factor that contributes to the manifestation of many of these neurodegenerative disorders. It is unquestionably a complex interaction with other factors such as genetics, age, and environment. This endorses the "multiple hit hypothesis". Consequently, if the host has a genetic susceptibility coupled to an age-related weakened immune system, this makes them more susceptible to the virus/bacteria-related infection. This may trigger the onset of chronic cytotoxic neuroinflammatory processes leading to protein dyshomeostasis and accumulation, and finally, these events lead to neuronal destruction. Here, we differentiate "neuroinflammation" and "inflammation" with regard to the involvement of the blood-brain barrier, which seems to be intact in the case of neuroinflammation but defect in the case of inflammation. There is a neuroinflammation-inflammation continuum with regard to virus-induced brain affection. Therefore, we propose a staging of this process, which might be further developed by adding blood- and CSF parameters, their stage-dependent composition and stage-dependent severeness grade. If so, this might be suitable to optimise therapeutic strategies to fight brain neuroinflammation in its beginning and avoid inflammation at all.}, } @article {pmid38261020, year = {2024}, author = {Ricci, V and Mezian, K and Chang, KV and Onishi, K and Kara, M and Naňka, O and Özçakar, L}, title = {Ultrasound-guided injection of the ankle joint: cadaveric investigation of the anterolateral approach.}, journal = {Surgical and radiologic anatomy : SRA}, volume = {46}, number = {2}, pages = {241-248}, pmid = {38261020}, issn = {1279-8517}, mesh = {Humans ; *Ankle Joint/diagnostic imaging ; Cadaver ; Injections, Intra-Articular/methods ; Ultrasonography, Interventional/methods ; }, abstract = {OBJECTIVE: Injection of the tibiotalar (TT) joint is commonly performed in clinical practice under ultrasound (US) guidance using an anteromedial approach. However, in some patients, this approach may be technically challenging due to post-traumatic and/or degenerative bony changes. Therefore, the aim of this cadaveric investigation was to demonstrate the feasibility of the ultrasound-guided (USG) injection of the ankle joint via the anterolateral sulcus (ALS) by confirming the dye placement/distribution inside the articular space. Likewise, the safety of the procedure has also been evaluated by measuring the distance between the needle and the intermediate dorsal cutaneous nerve of the foot.

DESIGN: A descriptive laboratory study with eight embalmed cadaveric ankles using the Fix for Life (F4L) method was performed at the setting of an academic institution. The interventional technique and the related anatomical findings were illustrated. During the injection, the needle was advanced into the TT joint through the ALS under US guidance, i.e., in-plane anterior-to-posterior approach. With the objective to confirm its correct placement, the needle was kept in situ and-to demonstrate the location of the dye inside the articular space-all eight ankles were injected with 3 mL of green color dye. Thereafter, a layer-by-layer anatomical dissection was performed on all four cadavers.

RESULTS: The position of the needle's tip within the ALS was confirmed in all specimens. Accurate placement of the dye inside the articular space of the ankle was confirmed in seven of the eight cadaveric ankles, with 87.5% of accuracy. Herewith, unintentional spilling of the dye within the superficial soft tissues was reported in two of the eight ankles (25.0%). The mean distance between the needle and the intermediate dorsal cutaneous nerve of the foot, measured in all eight procedures, was 3 cm.

CONCLUSION: USG injection of the ALS using the in-plane, anterior-to-posterior approach can accurately place the injectate inside the articular space.

CLINICAL RELEVANCE: This cadaveric investigation described the accuracy and potential pitfalls of USG injection of the ankle via the anterolateral approach which represents an alternative technique in patients with reduced accessibility of the anteromedial recess due to degenerative and/or post-traumatic bony changes.}, } @article {pmid38260713, year = {2023}, author = {Geraci, J and Bhargava, R and Qorri, B and Leonchyk, P and Cook, D and Cook, M and Sie, F and Pani, L}, title = {Machine learning hypothesis-generation for patient stratification and target discovery in rare disease: our experience with Open Science in ALS.}, journal = {Frontiers in computational neuroscience}, volume = {17}, number = {}, pages = {1199736}, pmid = {38260713}, issn = {1662-5188}, abstract = {INTRODUCTION: Advances in machine learning (ML) methodologies, combined with multidisciplinary collaborations across biological and physical sciences, has the potential to propel drug discovery and development. Open Science fosters this collaboration by releasing datasets and methods into the public space; however, further education and widespread acceptance and adoption of Open Science approaches are necessary to tackle the plethora of known disease states.

MOTIVATION: In addition to providing much needed insights into potential therapeutic protein targets, we also aim to demonstrate that small patient datasets have the potential to provide insights that usually require many samples (>5,000). There are many such datasets available and novel advancements in ML can provide valuable insights from these patient datasets.

PROBLEM STATEMENT: Using a public dataset made available by patient advocacy group AnswerALS and a multidisciplinary Open Science approach with a systems biology augmented ML technology, we aim to validate previously reported drug targets in ALS and provide novel insights about ALS subpopulations and potential drug targets using a unique combination of ML methods and graph theory.

METHODOLOGY: We use NetraAI to generate hypotheses about specific patient subpopulations, which were then refined and validated through a combination of ML techniques, systems biology methods, and expert input.

RESULTS: We extracted 8 target classes, each comprising of several genes that shed light into ALS pathophysiology and represent new avenues for treatment. These target classes are broadly categorized as inflammation, epigenetic, heat shock, neuromuscular junction, autophagy, apoptosis, axonal transport, and excitotoxicity. These findings are not mutually exclusive, and instead represent a systematic view of ALS pathophysiology. Based on these findings, we suggest that simultaneous targeting of ALS has the potential to mitigate ALS progression, with the plausibility of maintaining and sustaining an improved quality of life (QoL) for ALS patients. Even further, we identified subpopulations based on disease onset.

CONCLUSION: In the spirit of Open Science, this work aims to bridge the knowledge gap in ALS pathophysiology to aid in diagnostic, prognostic, and therapeutic strategies and pave the way for the development of personalized treatments tailored to the individual's needs.}, } @article {pmid38260655, year = {2024}, author = {Chen, D and Philippidou, P and Brenha, BF and Schaffer, AE and Miranda, HC}, title = {Scalable, optically-responsive human neuromuscular junction model reveals convergent mechanisms of synaptic dysfunction in familial ALS.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2024.01.11.575304}, pmid = {38260655}, issn = {2692-8205}, support = {K01 NS116119/NS/NINDS NIH HHS/United States ; R01 NS114510/NS/NINDS NIH HHS/United States ; R01 NS121374/NS/NINDS NIH HHS/United States ; }, abstract = {Neuromuscular junctions (NMJs) are specialized synapses that mediate communication between motor neurons and skeletal muscles and are essential for movement. The degeneration of this system can lead to symptoms observed in neuromuscular and motor neuron diseases. Studying these synapses and their degeneration has proven challenging. Prior NMJ studies heavily relied upon the use of mouse, chick, or isolated primary human cells, which have demonstrated limited fidelity for disease modeling. To enable the study of NMJ dysfunction and model genetic diseases, we, and others, have developed methods to generate human NMJs from pluripotent stem cells (PSCs), embryonic stem cells, and induced pluripotent stem cells. However, published studies have highlighted technical limitations associated with these complex in vitro NMJ models. In this study, we developed a robust PSC-derived motor neuron and skeletal muscle co-culture method, and demonstrated its sensitivity in modeling motor neuron disease. Our method spontaneously and reproducibly forms human NMJs. We developed multiwell-multielectrode array (MEA) parameters to quantify the activity of PSC-derived skeletal muscles, as well as measured the electrophysiological activity of functional human PSC-derived NMJs. We further leveraged our method to morphologically and functionally assess NMJs from the familial amyotrophic lateral sclerosis (fALS) PSCs, C9orf72 hexanucleotide (G4C2)n repeat expansion (HRE), SOD1 [A5V] , and TDP43 [G298S] to define the reproducibility and sensitivity of our system. We observed a significant decrease in the numbers and activity of PSC-derived NMJs developed from the different ALS lines compared to their respective controls. Furthermore, we evaluated a therapeutic candidate undergoing clinical trials and observed a variant-dependent rescue of functionality of NMJs. Our newly developed method provides a platform for the systematic investigation of genetic causes of NMJ neurodegeneration and highlights the need for therapeutic avenues to consider patient genotype.}, } @article {pmid38260601, year = {2024}, author = {Bosco, DB and Kremen, V and Haruwaka, K and Zhao, S and Wang, L and Ebner, BA and Zheng, J and Dheer, A and Perry, JF and Xie, M and Nguyen, AT and Worrell, GA and Wu, LJ}, title = {Impaired microglial phagocytosis promotes seizure development.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {38260601}, issn = {2692-8205}, support = {R01 NS088627/NS/NINDS NIH HHS/United States ; R01 NS112144/NS/NINDS NIH HHS/United States ; R35 NS132326/NS/NINDS NIH HHS/United States ; }, abstract = {In the central nervous system, triggering receptor expressed on myeloid cells 2 (TREM2) is exclusively expressed by microglia and is critical for microglial proliferation, migration, and phagocytosis. TREM2 plays an important role in neurodegenerative diseases, such as Alzheimer's disease and amyotrophic lateral sclerosis. However, little is known about the role TREM2 plays in epileptogenesis. To investigate this, we utilized TREM2 knockout (KO) mice within the murine intra-amygdala kainic acid seizure model. Electroencephalographic analysis, immunocytochemistry, and RNA sequencing revealed that TREM2 deficiency significantly promoted seizure-induced pathology. We found that TREM2 KO increased both acute status epilepticus and spontaneous recurrent seizures characteristic of chronic focal epilepsy. Mechanistically, phagocytic clearance of damaged neurons by microglia was impaired in TREM2 KO mice and the reduced phagocytic capacity correlated with increased spontaneous seizures. Analysis of human tissue from patients who underwent surgical resection for drug resistant temporal lobe epilepsy also showed a negative correlation between microglial phagocytic activity and focal to bilateral tonic-clonic generalized seizure history. These results indicate that microglial TREM2 and phagocytic activity may be important to epileptogenesis and the progression of focal temporal lobe epilepsy.}, } @article {pmid38260395, year = {2024}, author = {Evangelista, BA and Ragusa, JV and Pellegrino, K and Wu, Y and Quiroga-Barber, IY and Cahalan, SR and Arooji, OK and Madren, JA and Schroeter, S and Cozzarin, J and Xie, L and Chen, X and White, KK and Ezzell, JA and Iannone, MA and Cohen, S and Traub, RE and Li, X and Bedlack, R and Phanstiel, DH and Meeker, R and Stanley, N and Cohen, TJ}, title = {TDP-43 pathology links innate and adaptive immunity in amyotrophic lateral sclerosis.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2024.01.07.574541}, pmid = {38260395}, issn = {2692-8205}, support = {R21 AG071229/AG/NIA NIH HHS/United States ; T35 AG038047/AG/NIA NIH HHS/United States ; }, abstract = {Amyotrophic lateral sclerosis is the most common fatal motor neuron disease. Approximately 90% of ALS patients exhibit pathology of the master RNA regulator, Transactive Response DNA Binding protein (TDP-43). Despite the prevalence TDP-43 pathology in ALS motor neurons, recent findings suggest immune dysfunction is a determinant of disease progression in patients. Whether TDP-43 pathology elicits disease-modifying immune responses in ALS remains underexplored. In this study, we demonstrate that TDP-43 pathology is internalized by antigen presenting cells, causes vesicle rupture, and leads to innate and adaptive immune cell activation. Using a multiplex imaging platform, we observed interactions between innate and adaptive immune cells near TDP-43 pathological lesions in ALS brain. We used a mass cytometry-based whole-blood stimulation assay to provide evidence that ALS patient peripheral immune cells exhibit responses to TDP-43 aggregates. Taken together, this study provides a novel link between TDP-43 pathology and ALS immune dysfunction, and further highlights the translational and diagnostic implications of monitoring and manipulating the ALS immune response.}, } @article {pmid38260379, year = {2025}, author = {Zhu, Y and Cho, K and Lacin, H and Zhu, Y and DiPaola, JT and Wilson, BA and Patti, GJ and Skeath, JB}, title = {Loss of dihydroceramide desaturase drives neurodegeneration by disrupting endoplasmic reticulum and lipid droplet homeostasis in glial cells.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {38260379}, issn = {2692-8205}, support = {P30 CA091842/CA/NCI NIH HHS/United States ; P30 DK020579/DK/NIDDK NIH HHS/United States ; R01 NS036570/NS/NINDS NIH HHS/United States ; R01 NS122903/NS/NINDS NIH HHS/United States ; }, abstract = {Dihydroceramide desaturases convert dihydroceramides to ceramides, the precursors of all complex sphingolipids. Reduction of DEGS1 dihydroceramide desaturase function causes pediatric neurodegenerative disorder hypomyelinating leukodystrophy-18 (HLD-18). We discovered that infertile crescent (ifc), the Drosophila DEGS1 homolog, is expressed primarily in glial cells to promote CNS development by guarding against neurodegeneration. Loss of ifc causes massive dihydroceramide accumulation and severe morphological defects in cortex glia, including endoplasmic reticulum (ER) expansion, failure of neuronal ensheathment, and lipid droplet depletion. RNAi knockdown of the upstream ceramide synthase schlank in glia of ifc mutants rescues ER expansion, suggesting dihydroceramide accumulation in the ER drives this phenotype. RNAi knockdown of ifc in glia but not neurons drives neuronal cell death, suggesting that ifc function in glia promotes neuronal survival. Our work identifies glia as the primary site of disease progression in HLD-18 and may inform on juvenile forms of ALS, which also feature elevated dihydroceramide levels.}, } @article {pmid38260082, year = {2023}, author = {Norgren, J and Kåreholt, I and Sindi, S}, title = {Is there evidence of a ketogenic effect of coconut oil? Commentary: Effect of the Mediterranean diet supplemented with nicotinamide riboside and pterostilbene and/or coconut oil on anthropometric variables in amyotrophic lateral sclerosis. A pilot study.}, journal = {Frontiers in nutrition}, volume = {10}, number = {}, pages = {1333933}, pmid = {38260082}, issn = {2296-861X}, } @article {pmid38259506, year = {2023}, author = {Gallo, JM and Nishimura, A and Haapasalo, A}, title = {Editorial: Molecular mechanisms underlying C9orf72 neurodegeneration, volume II.}, journal = {Frontiers in cellular neuroscience}, volume = {17}, number = {}, pages = {1357319}, pmid = {38259506}, issn = {1662-5102}, } @article {pmid38259504, year = {2023}, author = {Rashid, S and Dimitriadi, M}, title = {Autophagy in spinal muscular atrophy: from pathogenic mechanisms to therapeutic approaches.}, journal = {Frontiers in cellular neuroscience}, volume = {17}, number = {}, pages = {1307636}, pmid = {38259504}, issn = {1662-5102}, abstract = {Spinal muscular atrophy (SMA) is a devastating neuromuscular disorder caused by the depletion of the ubiquitously expressed survival motor neuron (SMN) protein. While the genetic cause of SMA has been well documented, the exact mechanism(s) by which SMN depletion results in disease progression remain elusive. A wide body of evidence has highlighted the involvement and dysregulation of autophagy in SMA. Autophagy is a highly conserved lysosomal degradation process which is necessary for cellular homeostasis; defects in the autophagic machinery have been linked with a wide range of neurodegenerative disorders, including amyotrophic lateral sclerosis, Alzheimer's disease and Parkinson's disease. The pathway is particularly known to prevent neurodegeneration and has been suggested to act as a neuroprotective factor, thus presenting an attractive target for novel therapies for SMA patients. In this review, (a) we provide for the first time a comprehensive summary of the perturbations in the autophagic networks that characterize SMA development, (b) highlight the autophagic regulators which may play a key role in SMA pathogenesis and (c) propose decreased autophagic flux as the causative agent underlying the autophagic dysregulation observed in these patients.}, } @article {pmid38256091, year = {2024}, author = {Iskusnykh, IY and Zakharova, AA and Kryl'skii, ED and Popova, TN}, title = {Aging, Neurodegenerative Disorders, and Cerebellum.}, journal = {International journal of molecular sciences}, volume = {25}, number = {2}, pages = {}, pmid = {38256091}, issn = {1422-0067}, mesh = {Humans ; *Neurodegenerative Diseases ; Cerebellum ; *Alzheimer Disease ; *Huntington Disease ; Aging ; }, abstract = {An important part of the central nervous system (CNS), the cerebellum is involved in motor control, learning, reflex adaptation, and cognition. Diminished cerebellar function results in the motor and cognitive impairment observed in patients with neurodegenerative disorders such as Alzheimer's disease (AD), vascular dementia (VD), Parkinson's disease (PD), Huntington's disease (HD), spinal muscular atrophy (SMA), amyotrophic lateral sclerosis (ALS), Friedreich's ataxia (FRDA), and multiple sclerosis (MS), and even during the normal aging process. In most neurodegenerative disorders, impairment mainly occurs as a result of morphological changes over time, although during the early stages of some disorders such as AD, the cerebellum also serves a compensatory function. Biological aging is accompanied by changes in cerebellar circuits, which are predominantly involved in motor control. Despite decades of research, the functional contributions of the cerebellum and the underlying molecular mechanisms in aging and neurodegenerative disorders remain largely unknown. Therefore, this review will highlight the molecular and cellular events in the cerebellum that are disrupted during the process of aging and the development of neurodegenerative disorders. We believe that deeper insights into the pathophysiological mechanisms of the cerebellum during aging and the development of neurodegenerative disorders will be essential for the design of new effective strategies for neuroprotection and the alleviation of some neurodegenerative disorders.}, } @article {pmid38256050, year = {2024}, author = {Bruno, A and Milillo, C and Anaclerio, F and Buccolini, C and Dell'Elice, A and Angilletta, I and Gatta, M and Ballerini, P and Antonucci, I}, title = {Perinatal Tissue-Derived Stem Cells: An Emerging Therapeutic Strategy for Challenging Neurodegenerative Diseases.}, journal = {International journal of molecular sciences}, volume = {25}, number = {2}, pages = {}, pmid = {38256050}, issn = {1422-0067}, mesh = {Female ; Pregnancy ; Humans ; *Neurodegenerative Diseases/therapy ; *Alzheimer Disease ; *Huntington Disease/therapy ; *Parkinson Disease/therapy ; Stem Cells ; }, abstract = {Over the past 20 years, stem cell therapy has been considered a promising option for treating numerous disorders, in particular, neurodegenerative disorders. Stem cells exert neuroprotective and neurodegenerative benefits through different mechanisms, such as the secretion of neurotrophic factors, cell replacement, the activation of endogenous stem cells, and decreased neuroinflammation. Several sources of stem cells have been proposed for transplantation and the restoration of damaged tissue. Over recent decades, intensive research has focused on gestational stem cells considered a novel resource for cell transplantation therapy. The present review provides an update on the recent preclinical/clinical applications of gestational stem cells for the treatment of protein-misfolding diseases including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD) and amyotrophic lateral sclerosis (ALS). However, further studies should be encouraged to translate this promising therapeutic approach into the clinical setting.}, } @article {pmid38254647, year = {2023}, author = {Lauria, G and Curcio, R and Tucci, P}, title = {A Machine Learning Approach for Highlighting microRNAs as Biomarkers Linked to Amyotrophic Lateral Sclerosis Diagnosis and Progression.}, journal = {Biomolecules}, volume = {14}, number = {1}, pages = {}, pmid = {38254647}, issn = {2218-273X}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/genetics ; Biomarkers ; Machine Learning ; *MicroRNAs/genetics ; }, abstract = {Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive loss of motor neurons in the brain and spinal cord. The early diagnosis of ALS can be challenging, as it usually depends on clinical examination and the exclusion of other possible causes. In this regard, the analysis of miRNA expression profiles in biofluids makes miRNAs promising non-invasive clinical biomarkers. Due to the increasing amount of scientific literature that often provides controversial results, this work aims to deepen the understanding of the current state of the art on this topic using a machine-learning-based approach. A systematic literature search was conducted to analyze a set of 308 scientific articles using the MySLR digital platform and the Latent Dirichlet Allocation (LDA) algorithm. Two relevant topics were identified, and the articles clustered in each of them were analyzed and discussed in terms of biomolecular mechanisms, as well as in translational and clinical settings. Several miRNAs detected in the tissues and biofluids of ALS patients, including blood and cerebrospinal fluid (CSF), have been linked to ALS diagnosis and progression. Some of them may represent promising non-invasive clinical biomarkers. In this context, future scientific priorities and goals have been proposed.}, } @article {pmid38254150, year = {2024}, author = {Khalil, B and Linsenmeier, M and Smith, CL and Shorter, J and Rossoll, W}, title = {Nuclear-import receptors as gatekeepers of pathological phase transitions in ALS/FTD.}, journal = {Molecular neurodegeneration}, volume = {19}, number = {1}, pages = {8}, pmid = {38254150}, issn = {1750-1326}, support = {R33NS110960/NS/NINDS NIH HHS/United States ; R21AG061784/AG/NIA NIH HHS/United States ; RF1AG076122/AG/NIA NIH HHS/United States ; R01 GM099836/GM/NIGMS NIH HHS/United States ; R33 NS110960/NS/NINDS NIH HHS/United States ; R21 AG065854/AG/NIA NIH HHS/United States ; R01GM099836/GM/NIGMS NIH HHS/United States ; R21 AG079609/AG/NIA NIH HHS/United States ; R21AG065854/AG/NIA NIH HHS/United States ; R01 AG077771/AG/NIA NIH HHS/United States ; RF1AG068581/AG/NIA NIH HHS/United States ; W81XWH-20–1-0242//Department of Defense/ ; }, mesh = {Humans ; *Frontotemporal Dementia ; *Amyotrophic Lateral Sclerosis ; Active Transport, Cell Nucleus ; DNA-Binding Proteins ; *Prions ; }, abstract = {Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are fatal neurodegenerative disorders on a disease spectrum that are characterized by the cytoplasmic mislocalization and aberrant phase transitions of prion-like RNA-binding proteins (RBPs). The common accumulation of TAR DNA-binding protein-43 (TDP-43), fused in sarcoma (FUS), and other nuclear RBPs in detergent-insoluble aggregates in the cytoplasm of degenerating neurons in ALS/FTD is connected to nuclear pore dysfunction and other defects in the nucleocytoplasmic transport machinery. Recent advances suggest that beyond their canonical role in the nuclear import of protein cargoes, nuclear-import receptors (NIRs) can prevent and reverse aberrant phase transitions of TDP-43, FUS, and related prion-like RBPs and restore their nuclear localization and function. Here, we showcase the NIR family and how they recognize cargo, drive nuclear import, and chaperone prion-like RBPs linked to ALS/FTD. We also discuss the promise of enhancing NIR levels and developing potentiated NIR variants as therapeutic strategies for ALS/FTD and related neurodegenerative proteinopathies.}, } @article {pmid38254109, year = {2024}, author = {Nagy, ZF and Pál, M and Engelhardt, JI and Molnár, MJ and Klivényi, P and Széll, M}, title = {Beyond C9orf72: repeat expansions and copy number variations as risk factors of amyotrophic lateral sclerosis across various populations.}, journal = {BMC medical genomics}, volume = {17}, number = {1}, pages = {30}, pmid = {38254109}, issn = {1755-8794}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics ; *C9orf72 Protein/genetics ; DNA Copy Number Variations ; Genes, Regulator ; Risk Factors ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder which is characterized by the loss of both upper and lower motor neurons in the central nervous system. In a significant fraction of ALS cases - irrespective of family history- a genetic background may be identified. The genetic background of ALS shows a high variability from one ethnicity to another. The most frequent genetic cause of ALS is the repeat expansion of the C9orf72 gene. With the emergence of next-generation sequencing techniques and copy number alteration calling tools the focus in ALS genetics has shifted from disease causing genes and mutations towards genetic susceptibility and risk factors.In this review we aimed to summarize the most widely recognized and studied ALS linked repeat expansions and copy number variations other than the hexanucleotide repeat expansion in the C9orf72 gene. We compare and contrast their involvement and phenotype modifying roles in ALS among different populations.}, } @article {pmid38253707, year = {2024}, author = {El-Malla, SF and Hamza, AA and Elagamy, SH}, title = {Simultaneous determination of meloxicam and bupivacaine via a novel modified dual wavelength method and an advanced chemometric approach.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {1893}, pmid = {38253707}, issn = {2045-2322}, mesh = {Meloxicam ; *Chemometrics ; *Bupivacaine ; Chromatography, High Pressure Liquid ; Spectrophotometry ; }, abstract = {This study presents two spectrophotometric methods; a novel dual wavelength-derivative spectrophotometry and multivariate curve resolution-alternating least squares (MCR-ALS) for the simultaneous determination of a fixed dose combination of bupivacaine (BUP) and meloxicam (MEL) in a ratio of 30:1. The extended UV spectrum of MEL enables its direct determination at λmax 360 nm with no interference from BUP. The determination of BUP was unfeasible directly because the UV spectra of both drugs are moderately overlapped over the wavelength range of 250-450 nm, thus new chemometric based spectrophotometric methods should be developed for its determination. Dual wavelength-derivative method was employed based on using first derivative spectra. The selected dual wavelengths for determination BUP were 274.6 nm and 374.6 nm where the dA/dλ amplitudes differences for MET are equal to zero. MCR-ALS is advanced chemometric tool that enables analysis of multicomponent samples in complex matrices with high resolution based on the decomposition of signal/spectral data into the pure spectra and corresponding concentration profile. The figures of merits for MCR model show that there is a good agreement between the actual and predicted concentrations for MEL and BUP. The methods were validated and statistically compared with a reported HPLC method.}, } @article {pmid38253550, year = {2024}, author = {Voorhees, J and Bailey, S and Waterman, H and Checkland, K}, title = {A paradox of problems in accessing general practice: a qualitative participatory case study.}, journal = {The British journal of general practice : the journal of the Royal College of General Practitioners}, volume = {74}, number = {739}, pages = {e104-e112}, pmid = {38253550}, issn = {1478-5242}, mesh = {Humans ; *General Practice ; Qualitative Research ; Family Practice ; Focus Groups ; England ; }, abstract = {BACKGROUND: Despite longstanding problems of access to general practice, attempts to understand and address the issues do not adequately include perspectives of the people providing or using care, nor do they use established theories of access to understand complexity.

AIM: To understand problems of access to general practice from the multiple perspectives of service users and staff using an applied theory of access.

DESIGN AND SETTING: A qualitative participatory case study in an area of northwest England.

METHOD: A community-based participatory approach was used with qualitative interviews, focus groups, and observation to understand perspectives about accessing general practice. Data were collected between October 2015 and October 2016. Inductive and abductive analysis, informed by Levesque et al's theory of access, allowed the team to identify complexities and relationships between interrelated problems.

RESULTS: This study presents a paradox of problems in accessing general practice, in which the demand on general practice both creates and hides unmet need in the population. Data show how reactive rules to control demand have undermined important aspects of care, such as continuity. The layers of rules and decreased continuity create extra work for practice staff, clinicians, and patients. Complicated rules, combined with a lack of capacity to reach out or be flexible, leave many patients, including those with complex and/or unrecognised health needs, unable to navigate the system to access care. This relationship between demand and unmet need exacerbates existing health inequities.

CONCLUSION: Understanding the paradox of access problems allows for different targets for change and different solutions to free up capacity in general practice to address the unmet need in the population.}, } @article {pmid38253209, year = {2024}, author = {Yusuf, IO and Parsi, S and Ostrow, LW and Brown, RH and Thompson, PR and Xu, Z}, title = {PAD2 dysregulation and aberrant protein citrullination feature prominently in reactive astrogliosis and myelin protein aggregation in sporadic ALS.}, journal = {Neurobiology of disease}, volume = {192}, number = {}, pages = {106414}, pmid = {38253209}, issn = {1095-953X}, support = {R01 NS118145/NS/NINDS NIH HHS/United States ; R35 GM118112/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Humans ; Mice ; *Amyotrophic Lateral Sclerosis/metabolism ; *Citrullination ; Gliosis/metabolism ; Hydrolases/genetics/metabolism ; Myelin Proteins/metabolism ; Myelin Sheath/pathology ; Protein Aggregates ; Protein-Arginine Deiminase Type 2/metabolism ; Protein-Arginine Deiminases/metabolism ; Proteins/metabolism ; Spinal Cord/pathology ; }, abstract = {Alteration in protein citrullination (PC), a common posttranslational modification (PTM), contributes to pathogenesis in various inflammatory disorders. We previously reported that PC and protein arginine deiminase 2 (PAD2), the predominant enzyme isoform that catalyzes this PTM in the central nervous system (CNS), are altered in mouse models of amyotrophic lateral sclerosis (ALS). We now demonstrate that PAD2 expression and PC are altered in human postmortem ALS spinal cord and motor cortex compared to controls, increasing in astrocytes while trending lower in neurons. Furthermore, PC is enriched in protein aggregates that contain the myelin proteins PLP and MBP in ALS. These results confirm our findings in ALS mouse models and suggest that altered PAD2 and PC contribute to neurodegeneration in ALS.}, } @article {pmid38252383, year = {2024}, author = {Vassileff, N and Spiers, JG and Lee, JD and Woodruff, TM and Ebrahimie, E and Mohammadi Dehcheshmeh, M and Hill, AF and Cheng, L}, title = {A Panel of miRNA Biomarkers Common to Serum and Brain-Derived Extracellular Vesicles Identified in Mouse Model of Amyotrophic Lateral Sclerosis.}, journal = {Molecular neurobiology}, volume = {61}, number = {8}, pages = {5901-5915}, pmid = {38252383}, issn = {1559-1182}, support = {GNT1041413//National Health and Medical Research Council/ ; }, mesh = {Animals ; *Amyotrophic Lateral Sclerosis/blood/genetics/pathology/metabolism ; *Extracellular Vesicles/metabolism ; *MicroRNAs/genetics/metabolism/blood ; *Disease Models, Animal ; *Biomarkers/blood/metabolism ; *Brain/metabolism/pathology ; Mice ; Mice, Transgenic ; DNA-Binding Proteins/metabolism/genetics ; Male ; Mice, Inbred C57BL ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive motor neuron disease characterised by the deposition of aggregated proteins including TAR DNA-binding protein 43 (TDP-43) in vulnerable motor neurons and the brain. Extracellular vesicles (EVs) facilitate the spread of neurodegenerative diseases and can be easily accessed in the bloodstream. This study aimed to identify a panel of EV miRNAs that can capture the pathology occurring in the brain and peripheral circulation. EVs were isolated from the cortex (BDEVs) and serum (serum EVs) of 3 month-old and 6-month-old TDP-43*Q331K and TDP-43*WT mice. Following characterisation and miRNA isolation, the EVs underwent next-generation sequencing where 24 differentially packaged miRNAs were identified in the TDP-43*Q331K BDEVs and 7 in the TDP-43*Q331K serum EVs. Several miRNAs, including miR-183-5p, were linked to ALS. Additionally, miR-122-5p and miR-486b-5p were identified in both panels, demonstrating the ability of the serum EVs to capture the dysregulation occurring in the brain. This is the first study to identify miRNAs common to both the serum EVs and BDEVs in a mouse model of ALS.}, } @article {pmid38251257, year = {2024}, author = {Garamszegi, SP and Brzostowicki, DJ and Coyne, TM and Vontell, RT and Davis, DA}, title = {TDP-43 and Alzheimer's Disease Pathology in the Brain of a Harbor Porpoise Exposed to the Cyanobacterial Toxin BMAA.}, journal = {Toxins}, volume = {16}, number = {1}, pages = {}, pmid = {38251257}, issn = {2072-6651}, support = {GR012556 DAVIS//Herbert W. Hoover Foundation/ ; }, mesh = {Animals ; *Phocoena ; *Alzheimer Disease/chemically induced ; *Neurodegenerative Diseases ; Brain ; DNA-Binding Proteins ; }, abstract = {Cetaceans are well-regarded as sentinels for toxin exposure. Emerging studies suggest that cetaceans can also develop neuropathological changes associated with neurodegenerative disease. The occurrence of neuropathology makes cetaceans an ideal species for examining the impact of marine toxins on the brain across the lifespan. Here, we describe TAR DNA-binding protein 43 (TDP-43) proteinopathy and Alzheimer's disease (AD) neuropathological changes in a beached harbor porpoise (Phocoena phocoena) that was exposed to a toxin produced by cyanobacteria called β-N-methylamino-L-alanine (BMAA). We found pathogenic TDP-43 cytoplasmic inclusions in neurons throughout the cerebral cortex, midbrain and brainstem. P62/sequestosome-1, responsible for the autophagy of misfolded proteins, was observed in the amygdala, hippocampus and frontal cortex. Genes implicated in AD and TDP-43 neuropathology such as APP and TARDBP were expressed in the brain. AD neuropathological changes such as amyloid-β plaques, neurofibrillary tangles, granulovacuolar degeneration and Hirano bodies were present in the hippocampus. These findings further support the development of progressive neurodegenerative disease in cetaceans and a potential causative link to cyanobacterial toxins. Climate change, nutrient pollution and industrial waste are increasing the frequency of harmful cyanobacterial blooms. Cyanotoxins like BMAA that are associated with neurodegenerative disease pose an increasing public health risk.}, } @article {pmid38250776, year = {2024}, author = {Du, P and Zhang, X and Lian, X and Hölscher, C and Xue, G}, title = {O-GlcNAcylation and Its Roles in Neurodegenerative Diseases.}, journal = {Journal of Alzheimer's disease : JAD}, volume = {97}, number = {3}, pages = {1051-1068}, doi = {10.3233/JAD-230955}, pmid = {38250776}, issn = {1875-8908}, mesh = {Humans ; *Neurodegenerative Diseases/metabolism ; Protein Processing, Post-Translational ; Proteins/metabolism ; *Alzheimer Disease/pathology ; Acetylglucosamine/metabolism ; Disease Progression ; N-Acetylglucosaminyltransferases/metabolism ; }, abstract = {As a non-classical post-translational modification, O-linked β-N-acetylglucosamine (O-GlcNAc) modification (O-GlcNAcylation) is widely found in human organ systems, particularly in our brains, and is indispensable for healthy cell biology. With the increasing age of the global population, the incidence of neurodegenerative diseases is increasing, too. The common characteristic of these disorders is the aggregation of abnormal proteins in the brain. Current research has found that O-GlcNAcylation dysregulation is involved in misfolding or aggregation of these abnormal proteins to mediate disease progression, but the specific mechanism has not been defined. This paper reviews recent studies on O-GlcNAcylation's roles in several neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease, Machado-Joseph's disease, and giant axonal neuropathy, and shows that O-GlcNAcylation, as glucose metabolism sensor, mediating synaptic function, participating in oxidative stress response and signaling pathway conduction, directly or indirectly regulates characteristic pathological protein toxicity and affects disease progression. The existing results suggest that targeting O-GlcNAcylation will provide new ideas for clinical diagnosis, prevention, and treatment of neurodegenerative diseases.}, } @article {pmid38250183, year = {2024}, author = {Xia, J and Guo, S and Hu, F and Fan, L and Yu, L and Ye, J}, title = {Changes in Corneal Higher-Order Aberrations and Ocular Biometric Measurements after Phacoemulsification Combined with Goniosynechialysis in Primary Angle Closure/Glaucoma Patients.}, journal = {Journal of ophthalmology}, volume = {2024}, number = {}, pages = {5833543}, pmid = {38250183}, issn = {2090-004X}, abstract = {PURPOSE: To compare corneal higher-order aberrations (HOAs), refractive error, and ocular biological parameters before and after phacoemulsification combined with goniosynechialysis (Phaco-GSL) in primary angle closure/glaucoma (PAC/PACG) patients with different axial lengths (ALs).

METHODS: In this prospective study, cataract patients diagnosed with PAC/PACG were categorized into two groups based on their ALs: the short AL group (AL ≤ 22.5 mm) and the normal AL group (22.5 < AL ≤ 24.5 mm). The pre- and postsurgery measurements of intraocular pressure (IOP) and best-corrected visual acuity (BCVA) were conducted at 1 day, 1 week, 1 month, 3 months, 6 months, and 12 months. Additionally, the assessments included corneal HOAs, the number of antiglaucoma medications, visual field parameters, manifest refraction, and other ocular biological parameters before surgery and at the final follow-up.

RESULTS: Prior to surgery, the two groups exhibited no significant differences, except for AL, curvature value, and Z (4, 0) of the posterior corneal surface (all P < 0.01). Following surgery, BCVA improved, and IOP decreased significantly in both groups (P < 0.01). Both anterior and total corneal HOAs, along with Z (3, -3), increased in the two groups (all P < 0.05), with the normal AL group exhibiting a significantly greater increase in total cornea Z (3, -3) than the short AL group (P=0.047). The normal AL group also exhibited a slight tendency towards hyperopia (P < 0.01). Significant changes were observed in the visual field index and mean deviation in both groups (P < 0.05).

CONCLUSIONS: Phaco-GSL resulted in an increased corneal HOAs, particularly trefoil, with variations based on the patient's AL. Patients with normal ALs tended to shift towards hyperopia after surgery.}, } @article {pmid38249779, year = {2024}, author = {de Carvalho, M and Swash, M}, title = {[Not Available].}, journal = {Clinical neurophysiology practice}, volume = {9}, number = {}, pages = {27-38}, pmid = {38249779}, issn = {2467-981X}, abstract = {Accurate and rapid diagnosis of amyotrophic lateral sclerosis (ALS) is essential in order to provide accurate information for patient and family, to avoid time-consuming investigations and to permit an appropriate management plan. ALS is variable regarding presentation, disease progression, genetic profile and patient reaction to the diagnosis. It is obviously important to exclude treatable conditions but, in most patients, for experienced neurologists the diagnosis is clear-cut, depending on the presence of progressive upper and lower motor neuron signs. Patients with signs of restricted lower motor neuron (LMN) or upper motor neuron (UMN) dysfunction may present diagnostic difficulty, but electromyography (EMG) is often a determinant diagnostic test since it may exclude other disorders. Transcranial magnetic stimulation may aid detection of UMN dysfunction, and brain and spinal cord MRI, ultrasound and blood neurofilament measurements, have begun to have clinical impact, although none are themselves diagnostic tests. Several sets of diagnostic criteria have been proposed in the past; all rely on clinical LMN and UMN signs in different anatomic territories, EMG changes, exclusion of other disorders, and disease progression, in particular evidence of spreading to other anatomic territories. Fasciculations are a characteristic clinical feature and increased importance is now attached to fasciculation potentials detected by EMG, when associated with classical signs of denervation and reinnervation. The Gold Coast diagnostic criteria rely on the presence of UMN and LMN signs in one (or more) anatomic territory, or LMN signs in two (or more) anatomic territories, recognizing the fundamental clinical requirements of disease progression and exclusion of other diseases. Recent studies confirm a high sensitivity without loss of specificity using these Gold Coast criteria. In considering the diagnosis of ALS a critical question for future understanding is whether ALS should be considered a syndrome or a specific clinico-pathologic entity; this can only be addressed in the light of more complete knowledge.}, } @article {pmid38249738, year = {2023}, author = {Croucher, KM and Fleming, SM}, title = {ATP13A2 (PARK9) and basal ganglia function.}, journal = {Frontiers in neurology}, volume = {14}, number = {}, pages = {1252400}, pmid = {38249738}, issn = {1664-2295}, support = {R01 ES031124/ES/NIEHS NIH HHS/United States ; }, abstract = {ATP13A2 is a lysosomal protein involved in polyamine transport with loss of function mutations associated with multiple neurodegenerative conditions. These include early onset Parkinson's disease, Kufor-Rakeb Syndrome, neuronal ceroid lipofuscinosis, hereditary spastic paraplegia, and amyotrophic lateral sclerosis. While ATP13A2 mutations may result in clinical heterogeneity, the basal ganglia appear to be impacted in the majority of cases. The basal ganglia is particularly vulnerable to environmental exposures such as heavy metals, pesticides, and industrial agents which are also established risk factors for many neurodegenerative conditions. Not surprisingly then, impaired function of ATP13A2 has been linked to heavy metal toxicity including manganese, iron, and zinc. This review discusses the role of ATP13A2 in basal ganglia function and dysfunction, potential common pathological mechanisms in ATP13A2-related disorders, and how gene x environment interactions may contribute to basal ganglia dysfunction.}, } @article {pmid38249592, year = {2023}, author = {Jiang, Q and Guo, Y and Yang, T and Li, S and Hou, Y and Lin, J and Xiao, Y and Ou, R and Wei, Q and Shang, H}, title = {Cystatin C is associated with poor survival in amyotrophic lateral sclerosis patients.}, journal = {Frontiers in neuroscience}, volume = {17}, number = {}, pages = {1309568}, pmid = {38249592}, issn = {1662-4548}, abstract = {BACKGROUND: Cystatin C (CysC) levels in amyotrophic lateral sclerosis (ALS) have been found changes, however, the associations between serum CysC levels and the progression and survival of ALS remain largely unknown.

METHODS: A total of 1,086 ALS patients and 1,026 sex-age matched healthy controls (HCs) were enrolled in this study. Serum CysC, other renal function, and metabolic parameters were measured. Correlation analysis and binary logistic regression were used to explore the factors related to serum CysC. Kaplan-Meier curve and Cox regression model were used for survival analysis.

RESULTS: CysC levels were significantly higher in ALS patients compared to HCs (0.94 vs. 0.85 mg/L, p < 0.001). Compared with ALS patients with lower CysC levels, those with higher CysC levels had an older age of onset, significantly lower ALSFRS-R scores (40.1 vs. 41.3, p < 0.001), a faster disease progression rate (0.75 vs. 0.67, p = 0.011), and lower frontal lobe function scores (15.8 vs. 16.1, p = 0.020). In the correlation analysis, CysC levels were significantly negatively correlated with ALSFRS-R scores (r = -0.16, p < 0.001). Additionally, ALS patients with higher CysC levels had significantly shorter survival time (40.0 vs. 51.8, p < 0.001) compared to patients with lower CysC levels. Higher CysC levels were associated with a higher risk of death in Cox analysis (HR: 1.204, 95% CI: 1.012-1.433). However, when treatment was included in the model, the result was no longer significant.

CONCLUSION: CysC levels in ALS patients were higher compared to HCs. Higher CysC levels were associated with greater disease severity, faster progression rate and shorter survival, needing early intervention.}, } @article {pmid38249293, year = {2023}, author = {Krishnamurthy, K and Pradhan, RK}, title = {Emerging perspectives of synaptic biomarkers in ALS and FTD.}, journal = {Frontiers in molecular neuroscience}, volume = {16}, number = {}, pages = {1279999}, pmid = {38249293}, issn = {1662-5099}, abstract = {Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD) are debilitating neurodegenerative diseases with shared pathological features like transactive response DNA-binding protein of 43 kDa (TDP-43) inclusions and genetic mutations. Both diseases involve synaptic dysfunction, contributing to their clinical features. Synaptic biomarkers, representing proteins associated with synaptic function or structure, offer insights into disease mechanisms, progression, and treatment responses. These biomarkers can detect disease early, track its progression, and evaluate therapeutic efficacy. ALS is characterized by elevated neurofilament light chain (NfL) levels in cerebrospinal fluid (CSF) and blood, correlating with disease progression. TDP-43 is another key ALS biomarker, its mislocalization linked to synaptic dysfunction. In FTD, TDP-43 and tau proteins are studied as biomarkers. Synaptic biomarkers like neuronal pentraxins (NPs), including neuronal pentraxin 2 (NPTX2), and neuronal pentraxin receptor (NPTXR), offer insights into FTD pathology and cognitive decline. Advanced technologies, like machine learning (ML) and artificial intelligence (AI), aid biomarker discovery and drug development. Challenges in this research include technological limitations in detection, variability across patients, and translating findings from animal models. ML/AI can accelerate discovery by analyzing complex data and predicting disease outcomes. Synaptic biomarkers offer early disease detection, personalized treatment strategies, and insights into disease mechanisms. While challenges persist, technological advancements and interdisciplinary efforts promise to revolutionize the understanding and management of ALS and FTD. This review will explore the present comprehension of synaptic biomarkers in ALS and FTD and discuss their significance and emphasize the prospects and obstacles.}, } @article {pmid38249102, year = {2024}, author = {Bakaeva, M and Chetverikov, S and Starikov, S and Kendjieva, A and Khudaygulov, G and Chetverikova, D}, title = {Effect of Plant Growth-Promoting Bacteria on Antioxidant Status, Acetolactate Synthase Activity, and Growth of Common Wheat and Canola Exposed to Metsulfuron-Methyl.}, journal = {Journal of xenobiotics}, volume = {14}, number = {1}, pages = {79-95}, pmid = {38249102}, issn = {2039-4713}, support = {23-26-00097//Russian Science Foundation/ ; }, abstract = {Metsulfuron-methyl, a widely used herbicide, could cause damage to the sensitive plants in crop-rotation systems at extremely low levels in the soil. The potential of plant growth-promoting bacteria (PGPB) for enhancing the resistance of plants against herbicide stress has been discovered recently. Therefore, it is poorly understood how physiological processes occur in plants, while PGPB reduce the phytotoxicity of herbicides for agricultural crops. In greenhouse studies, the effect of strains Pseudomonas protegens DA1.2 and Pseudomonas chlororaphis 4CH on oxidative damage, acetolactate synthase (ALS), enzymatic and non-enzymatic antioxidants in canola (Brassica napus L.), and wheat (Triticum aestivum L.) were investigated under two levels (0.05 and 0.25 mg∙kg[-1]) of metsulfuron-methyl using spectrophotometric assays. The inoculation of herbicide-exposed wheat with bacteria significantly increased the shoots fresh weight (24-28%), amount of glutathione GSH (60-73%), and flavonoids (5-14%), as well as activity of ascorbate peroxidase (129-140%), superoxide dismutase SOD (35-49%), and ALS (50-57%). Bacterial treatment stimulated the activity of SOD (37-94%), ALS (65-73%), glutathione reductase (19-20%), and the accumulation of GSH (61-261%), flavonoids (17-22%), and shoots weight (27-33%) in herbicide-exposed canola. Simultaneous inoculation prevented lipid peroxidation induced by metsulfuron-methyl in sensitive plants. Based on the findings, it is possible that the protective role of bacterial strains against metsulfuron-metil is linked to antioxidant system activation.}, } @article {pmid38247879, year = {2024}, author = {Shehjar, F and Almarghalani, DA and Mahajan, R and Hasan, SA and Shah, ZA}, title = {The Multifaceted Role of Cofilin in Neurodegeneration and Stroke: Insights into Pathogenesis and Targeting as a Therapy.}, journal = {Cells}, volume = {13}, number = {2}, pages = {}, pmid = {38247879}, issn = {2073-4409}, support = {R01 NS112642/NS/NINDS NIH HHS/United States ; R01NS112642/NS/NINDS NIH HHS/United States ; }, mesh = {Humans ; *Actin Depolymerizing Factors ; alpha-Synuclein ; *Alzheimer Disease ; *Amyotrophic Lateral Sclerosis ; *Parkinson Disease ; *Stroke/metabolism ; }, abstract = {This comprehensive review explores the complex role of cofilin, an actin-binding protein, across various neurodegenerative diseases (Alzheimer's, Parkinson's, schizophrenia, amyotrophic lateral sclerosis (ALS), Huntington's) and stroke. Cofilin is an essential protein in cytoskeletal dynamics, and any dysregulation could lead to potentially serious complications. Cofilin's involvement is underscored by its impact on pathological hallmarks like Aβ plaques and α-synuclein aggregates, triggering synaptic dysfunction, dendritic spine loss, and impaired neuronal plasticity, leading to cognitive decline. In Parkinson's disease, cofilin collaborates with α-synuclein, exacerbating neurotoxicity and impairing mitochondrial and axonal function. ALS and frontotemporal dementia showcase cofilin's association with genetic factors like C9ORF72, affecting actin dynamics and contributing to neurotoxicity. Huntington's disease brings cofilin into focus by impairing microglial migration and influencing synaptic plasticity through AMPA receptor regulation. Alzheimer's, Parkinson's, and schizophrenia exhibit 14-3-3 proteins in cofilin dysregulation as a shared pathological mechanism. In the case of stroke, cofilin takes center stage, mediating neurotoxicity and neuronal cell death. Notably, there is a potential overlap in the pathologies and involvement of cofilin in various diseases. In this context, referencing cofilin dysfunction could provide valuable insights into the common pathologies associated with the aforementioned conditions. Moreover, this review explores promising therapeutic interventions, including cofilin inhibitors and gene therapy, demonstrating efficacy in preclinical models. Challenges in inhibitor development, brain delivery, tissue/cell specificity, and long-term safety are acknowledged, emphasizing the need for precision drug therapy. The call to action involves collaborative research, biomarker identification, and advancing translational efforts. Cofilin emerges as a pivotal player, offering potential as a therapeutic target. However, unraveling its complexities requires concerted multidisciplinary efforts for nuanced and effective interventions across the intricate landscape of neurodegenerative diseases and stroke, presenting a hopeful avenue for improved patient care.}, } @article {pmid38247869, year = {2024}, author = {Smeele, PH and Cesare, G and Vaccari, T}, title = {ALS' Perfect Storm: C9orf72-Associated Toxic Dipeptide Repeats as Potential Multipotent Disruptors of Protein Homeostasis.}, journal = {Cells}, volume = {13}, number = {2}, pages = {}, pmid = {38247869}, issn = {2073-4409}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics ; *C9orf72 Protein/genetics ; Dipeptides ; *Frontotemporal Dementia/genetics ; *Proteostasis ; }, abstract = {Protein homeostasis is essential for neuron longevity, requiring a balanced regulation between protein synthesis and degradation. The clearance of misfolded and aggregated proteins, mediated by autophagy and the ubiquitin-proteasome systems, maintains protein homeostasis in neurons, which are post-mitotic and thus cannot use cell division to diminish the burden of misfolded proteins. When protein clearance pathways are overwhelmed or otherwise disrupted, the accumulation of misfolded or aggregated proteins can lead to the activation of ER stress and the formation of stress granules, which predominantly attempt to restore the homeostasis by suppressing global protein translation. Alterations in these processes have been widely reported among studies investigating the toxic function of dipeptide repeats (DPRs) produced by G4C2 expansion in the C9orf72 gene of patients with amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). In this review, we outline the modalities of DPR-induced disruptions in protein homeostasis observed in a wide range of models of C9orf72-linked ALS/FTD. We also discuss the relative importance of each DPR for toxicity, possible synergies between DPRs, and discuss the possible functional relevance of DPR aggregation to disease pathogenesis. Finally, we highlight the interdependencies of the observed effects and reflect on the importance of feedback and feedforward mechanisms in their contribution to disease progression. A better understanding of DPR-associated disease pathogenesis discussed in this review might shed light on disease vulnerabilities that may be amenable with therapeutic interventions.}, } @article {pmid38246117, year = {2024}, author = {de Jonge, S and Potters, WV and Verhamme, C}, title = {Artificial intelligence for automatic classification of needle EMG signals: A scoping review.}, journal = {Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology}, volume = {159}, number = {}, pages = {41-55}, doi = {10.1016/j.clinph.2023.12.134}, pmid = {38246117}, issn = {1872-8952}, mesh = {Humans ; *Artificial Intelligence ; *Amyotrophic Lateral Sclerosis ; Electromyography ; Needles ; }, abstract = {OBJECTIVE: This scoping review provides an overview of artificial intelligence (AI), including machine and deep learning techniques, in the interpretation of clinical needle electromyography (nEMG) signals.

METHODS: A comprehensive search of Medline, Embase and Web of Science was conducted to find peer-reviewed journal articles. All papers published after 2010 were included. The methodological quality of the included studies was assessed with CLAIM (checklist for artificial intelligence in medical imaging).

RESULTS: 51 studies were identified that fulfilled the inclusion criteria. 61% used open-source EMGlab data set to develop models to classify nEMG signal in healthy, amyotrophic lateral sclerosis (ALS) and myopathy (25 subjects). Only two articles developed models to classify signals recorded at rest. Most articles reported high performance accuracies, but many were subject to bias and overtraining.

CONCLUSIONS: Current AI-models of nEMG signals are not sufficient for clinical implementation. Suggestions for future research include emphasizing the need for an optimal training and validation approach using large datasets of clinical nEMG data from a diverse patient population.

SIGNIFICANCE: The outcomes of this study and the suggestions made aim to contribute to developing AI-models that can effectively handle signal quality variability and are suitable for daily clinical practice in interpreting nEMG signals.}, } @article {pmid38245992, year = {2024}, author = {Robertson, DJ and Jeziorczak, PM and Aprahamian, CJ}, title = {Diaphragmatic pacing for respiratory failure in children.}, journal = {Seminars in pediatric surgery}, volume = {33}, number = {1}, pages = {151386}, doi = {10.1016/j.sempedsurg.2024.151386}, pmid = {38245992}, issn = {1532-9453}, mesh = {Child ; Humans ; *Amyotrophic Lateral Sclerosis/complications ; Diaphragm ; Phrenic Nerve/surgery ; *Respiratory Insufficiency/etiology/therapy ; }, abstract = {Diaphragm pacing is a ventilation strategy in respiratory failure. Most of the literature on pacing involves adults with common indications being spinal cord injury and amyotrophic lateral sclerosis (ALS). Previous reports in pediatric patients consist of case reports or small series; most describe direct phrenic nerve stimulation for central hypoventilation syndrome. This differs from adult reports that focus most commonly on spinal cord injuries and the rehabilitative nature of diaphragm pacing. This review describes the current state of diaphragm pacing in pediatric patients. Indications, current available technologies, surgical techniques, advantages, and pitfalls/problems are discussed.}, } @article {pmid38244886, year = {2024}, author = {DSouza, AA and Kulkarni, P and Ferris, CF and Amiji, MM and Bleier, BS}, title = {Mild repetitive TBI reduces brain-derived neurotrophic factor (BDNF) in the substantia nigra and hippocampus: A preclinical model for testing BDNF-targeted therapeutics.}, journal = {Experimental neurology}, volume = {374}, number = {}, pages = {114696}, pmid = {38244886}, issn = {1090-2430}, support = {P30 EY003790/EY/NEI NIH HHS/United States ; R01 NS108968/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Female ; Male ; Rats ; *Brain Concussion/complications ; *Brain Injuries, Traumatic/drug therapy/complications ; Brain-Derived Neurotrophic Factor/metabolism ; Hippocampus/metabolism ; Substantia Nigra/metabolism ; }, abstract = {Clinical studies have consistently shown that neurodegenerative diseases (NDs) such as Parkinson's disease, Alzheimer's disease, Amyotrophic Lateral Sclerosis, and Huntington's disease show absent or low levels of brain-derived neurotrophic factor (BDNF). Despite this relationship between BDNF and ND, only a few ND animal models have been able to recapitulate the low BDNF state, thereby hindering research into the therapeutic targeting of this important neurotrophic factor. In order to address this unmet need, we sought to develop a reproducible model of BDNF reduction by inducing traumatic brain injury (TBI) using a closed head momentum exchange injury model in mature 9-month-old male and female rats. Head impacts were repetitive and varied in intensity from mild to severe. BDNF levels, as assessed by ELISA, were significantly reduced in the hippocampus of both males and females as well as in the substantia nigra of males 12 days after mild TBI. However, we observed significant sexual dimorphism in multiple sequelae, including magnetic resonance imaging-determined vasogenic edema, astrogliosis (GFAP-activation), and microgliosis (Iba1 activation). This study provides an opportunity to investigate the mechanism of BDNF reduction in rodent models and provides a reliable paradigm to test BDNF-targeted therapeutics for the treatment of ND.}, } @article {pmid38244235, year = {2024}, author = {Kim, SH and Oh, KW and Noh, MY and Kwon, MS}, title = {Optimal Therapeutic Strategy of Bone Marrow-Originated Autologous Mesenchymal Stromal/Stem Cells for ALS.}, journal = {Stem cells translational medicine}, volume = {13}, number = {4}, pages = {309-316}, pmid = {38244235}, issn = {2157-6580}, support = {NRF//National Research Foundation/ ; MSIT; RS-2023-00265515//Korean government/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy ; Bone Marrow ; Biomarkers ; *Mesenchymal Stem Cells ; *Mesenchymal Stem Cell Transplantation/methods ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is characterized by selective and progressive neurodegenerative changes in motor neural networks. Given the system complexity, including anatomically distributed sites of degeneration from the motor cortex to the spinal cord and chronic pro-inflammatory conditions, a cell-based therapeutic strategy could be an alternative approach to treating ALS. Lessons from previous mesenchymal stromal/stem cell (MSC) trials in ALS realized the importance of 3 aspects in current and future MSC therapy, including the preparation of MSCs, administration routes and methods, and recipient-related factors. This review briefly describes the current status and future prerequisites for an optimal strategy using bone-marrow-originated MSCs to treat ALS. We suggest mandatory factors in the optimized therapeutic strategy focused on advanced therapy medicinal products produced according to Good Manufacturing Practice, an optimal administration method, the selection of proper patients, and the importance of biomarkers.}, } @article {pmid38244210, year = {2024}, author = {Xu, C and Diemant, T and Mariani, A and Di Pietro, ME and Mele, A and Liu, X and Passerini, S}, title = {Locally Concentrated Ionic Liquid Electrolytes for Wide-Temperature-Range Aluminum-Sulfur Batteries.}, journal = {Angewandte Chemie (International ed. in English)}, volume = {63}, number = {10}, pages = {e202318204}, doi = {10.1002/anie.202318204}, pmid = {38244210}, issn = {1521-3773}, support = {//China Sponsorship Council/ ; //Helmholtz Association/ ; MSCA EF Master Class 2018//Politecnico di Milano/ ; }, abstract = {Aluminum-sulfur (Al-S) batteries are promising energy storage devices due to their high theoretical capacity, low cost, and high safety. However, the high viscosity and inferior ion transport of conventionally used ionic liquid electrolytes (ILEs) limit the kinetics of Al-S batteries, especially at sub-zero temperatures. Herein, locally concentrated ionic liquid electrolytes (LCILE) formed via diluting the ILEs with non-solvating 1,2-difluorobenzene (dFBn) co-solvent are proposed for wide-temperature-range Al-S batteries. The addition of dFBn effectively promotes the fluidity and ionic conductivity without affecting the AlCl4 [-] /Al2 Cl7 [-] equilibrium, which preserves the reversible stripping/plating of aluminum and further promotes the overall kinetics of Al-S batteries. As a result, Al-S cells employing the LCILE exhibit higher specific capacity, better cyclability, and lower polarization with respect to the neat ILE in a wide temperature range from -20 to 40 °C. For instance, Al-S batteries employing the LCILE sustain a remarkable capacity of 507 mAh g[-1] after 300 cycles at 20 °C, while only 229 mAh g[-1] is delivered with the dFBn-free electrolyte under the same condition. This work demonstrates the favorable use of LCILEs for wide-temperature Al-S batteries.}, } @article {pmid38243956, year = {2024}, author = {Singh, S and Ahuja, A and Pathak, S}, title = {Potential Role of Oxidative Stress in the Pathophysiology of Neurodegenerative Disorders.}, journal = {Combinatorial chemistry & high throughput screening}, volume = {27}, number = {14}, pages = {2043-2061}, pmid = {38243956}, issn = {1875-5402}, mesh = {Humans ; *Oxidative Stress/drug effects ; *Neurodegenerative Diseases/drug therapy/metabolism ; *Antioxidants/pharmacology ; Reactive Oxygen Species/metabolism ; Animals ; Neuroprotective Agents/pharmacology/chemistry ; }, abstract = {Neurodegeneration causes premature death in the peripheral and central nervous system. Neurodegeneration leads to the accumulation of oxidative stress, inflammatory responses, and the generation of free radicals responsible for nervous disorders like amyotrophic lateral sclerosis, Alzheimer's disease, Parkinson's disease, and Huntington's disorders. Therefore, focus must be diverted towards treating and managing these disorders, as it is very challenging. Furthermore, effective therapies are also lacking, so the growing interest of the global market must be inclined towards developing newer therapeutic approaches that can intercept the progression of neurodegeneration. Emerging evidences of research findings suggest that antioxidant therapy has significant potential in modulating disease phenotypes. This makes them promising candidates for further investigation. This review focuses on the role of oxidative stress and reactive oxygen species in the pathological mechanisms of various neurodegenerative diseases, amyotrophic lateral sclerosis, Alzheimer's disease, Parkinson's disease, and Huntington's disorders and their neuroprotection. Additionally, it highlights the potential of antioxidant-based therapeutics in mitigating disease severity in humans and improving patient compliance. Ongoing extensive global research further sheds light on exploring new therapeutic targets for a deeper understanding of disease mechanisms in the field of medicine and biology targeting neurogenerative disorders.}, } @article {pmid38242131, year = {2024}, author = {Shum, C and Hedges, EC and Allison, J and Lee, YB and Arias, N and Cocks, G and Chandran, S and Ruepp, MD and Shaw, CE and Nishimura, AL}, title = {Mutations in FUS lead to synaptic dysregulation in ALS-iPSC derived neurons.}, journal = {Stem cell reports}, volume = {19}, number = {2}, pages = {187-195}, pmid = {38242131}, issn = {2213-6711}, support = {MR/N013255/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Adult ; Humans ; *Amyotrophic Lateral Sclerosis/pathology ; *Induced Pluripotent Stem Cells/metabolism ; Motor Neurons/metabolism ; Mutation ; Glutamates/metabolism ; RNA-Binding Protein FUS/genetics ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal, adult-onset neurodegenerative disorder characterized by progressive muscular weakness due to the selective loss of motor neurons. Mutations in the gene Fused in Sarcoma (FUS) were identified as one cause of ALS. Here, we report that mutations in FUS lead to upregulation of synaptic proteins, increasing synaptic activity and abnormal release of vesicles at the synaptic cleft. Consequently, FUS-ALS neurons showed greater vulnerability to glutamate excitotoxicity, which raised neuronal swellings (varicose neurites) and led to neuronal death. Fragile X mental retardation protein (FMRP) is an RNA-binding protein known to regulate synaptic protein translation, and its expression is reduced in the FUS-ALS lines. Collectively, our data suggest that a reduction of FMRP levels alters the synaptic protein dynamics, leading to synaptic dysfunction and glutamate excitotoxicity. Here, we present a mechanistic hypothesis linking dysregulation of peripheral translation with synaptic vulnerability in the pathogenesis of FUS-ALS.}, } @article {pmid38242117, year = {2024}, author = {Rautila, OS and Kaivola, K and Rautila, H and Hokkanen, L and Launes, J and Strandberg, TE and Laaksovirta, H and Palmio, J and Tienari, PJ}, title = {The shared ancestry between the C9orf72 hexanucleotide repeat expansion and intermediate-length alleles using haplotype sharing trees and HAPTK.}, journal = {American journal of human genetics}, volume = {111}, number = {2}, pages = {383-392}, pmid = {38242117}, issn = {1537-6605}, mesh = {Humans ; Alleles ; *Amyotrophic Lateral Sclerosis/genetics ; *C9orf72 Protein/genetics ; DNA Repeat Expansion/genetics ; Haplotypes/genetics ; Receptor Protein-Tyrosine Kinases/genetics ; *Trees/genetics ; }, abstract = {The C9orf72 hexanucleotide repeat expansion (HRE) is a common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The inheritance is autosomal dominant, but a high proportion of subjects with the mutation are simplex cases. One possible explanation is de novo expansions of unstable intermediate-length alleles (IAs). Using haplotype sharing trees (HSTs) with the haplotype analysis tool kit (HAPTK), we derived majority-based ancestral haplotypes of HRE samples and discovered that IAs containing ≥18-20 repeats share large haplotypes in common with the HRE. Using HSTs of HRE and IA samples, we demonstrate that the longer IA haplotypes are largely indistinguishable from HRE haplotypes and that several ≥18-20 IA haplotypes share over 5 Mb (>600 markers) haplotypes in common with the HRE haplotypes. These analysis tools allow physical understanding of the haplotype blocks shared with the majority-based ancestral haplotype. Our results demonstrate that the haplotypes with longer IAs belong to the same pool of haplotypes as the HRE and suggest that longer IAs represent potential premutation alleles.}, } @article {pmid38241787, year = {2024}, author = {Hromas, G and Jackson, CE and Cooper, DB and Sullivan, AC}, title = {Primary progressive aphasia and amyotrophic lateral sclerosis (PPA-ALS): A longitudinal case study.}, journal = {Applied neuropsychology. Adult}, volume = {}, number = {}, pages = {1-4}, doi = {10.1080/23279095.2024.2302833}, pmid = {38241787}, issn = {2327-9109}, abstract = {OBJECTIVE: Approximately 50% of patients with amyotrophic lateral sclerosis (ALS) experience cognitive decline, with frontotemporal dementia (FTD) accounting for up to 15% of these cases. Despite this, there is considerable delay in diagnosis, which affects patient care.

METHODS: We report longitudinal results of neuropsychological evaluations in a patient diagnosed with non-fluent/agrammatic primary progressive aphasia (nfvPPA) and amyotrophic lateral sclerosis (ALS). The patient, Ms. X, presented with progressive speech difficulties starting in her late-60's. Initial diagnosis was nfvPPA. After 4-5 years of progressive swallowing difficulties, as well as facial weakness, her diagnosis was modified to PPA-ALS.

RESULTS: Ms. X underwent neuropsychological evaluations three times over a period of five years. Results of evaluations were intact and stable over time, except for progressive loss of speech impacting her performance on a sentence repetition task.

CONCLUSION: This case study provides valuable insight into the overlap between PPA-ALS from a neuropsychological standpoint. The results reflect preserved cognitive skills in the context of loss of speech and motor abilities. This case study also shows the length of time between onset of symptoms and clear diagnosis, which often requires an immense amount of health literacy and personal advocacy on the part of the patient.}, } @article {pmid38241161, year = {2024}, author = {Klemmensen, MM and Borrowman, SH and Pearce, C and Pyles, B and Chandra, B}, title = {Mitochondrial dysfunction in neurodegenerative disorders.}, journal = {Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics}, volume = {21}, number = {1}, pages = {e00292}, pmid = {38241161}, issn = {1878-7479}, mesh = {Humans ; *Neurodegenerative Diseases/therapy/drug therapy ; Mitochondria ; Reactive Oxygen Species/therapeutic use ; *Alzheimer Disease/pathology ; *Mitochondrial Diseases/genetics/therapy ; }, abstract = {Recent advances in understanding the role of mitochondrial dysfunction in neurodegenerative diseases have expanded the opportunities for neurotherapeutics targeting mitochondria to alleviate symptoms and slow disease progression. In this review, we offer a historical account of advances in mitochondrial biology and neurodegenerative disease. Additionally, we summarize current knowledge of the normal physiology of mitochondria and the pathogenesis of mitochondrial dysfunction, the role of mitochondrial dysfunction in neurodegenerative disease, current therapeutics and recent therapeutic advances, as well as future directions for neurotherapeutics targeting mitochondrial function. A focus is placed on reactive oxygen species and their role in the disruption of telomeres and their effects on the epigenome. The effects of mitochondrial dysfunction in the etiology and progression of Alzheimer's disease, amyotrophic lateral sclerosis, Parkinson's disease, and Huntington's disease are discussed in depth. Current clinical trials for mitochondria-targeting neurotherapeutics are discussed.}, } @article {pmid38241160, year = {2024}, author = {López-Blanch, R and Salvador-Palmer, R and Oriol-Caballo, M and Moreno-Murciano, P and Dellinger, RW and Estrela, JM and Obrador, E}, title = {Nicotinamide riboside, pterostilbene and ibudilast protect motor neurons and extend survival in ALS mice.}, journal = {Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics}, volume = {21}, number = {1}, pages = {e00301}, pmid = {38241160}, issn = {1878-7479}, mesh = {Mice ; Animals ; Humans ; Superoxide Dismutase-1 ; *Amyotrophic Lateral Sclerosis/drug therapy ; Neuroinflammatory Diseases ; Tumor Necrosis Factor-alpha ; Endothelial Cells ; Hydrogen Peroxide ; Pilot Projects ; Motor Neurons ; Niacinamide/pharmacology/therapeutic use/*analogs & derivatives ; Mice, Transgenic ; Disease Models, Animal ; Superoxide Dismutase ; Spinal Cord ; *Indolizines ; *Pyrazoles ; *Pyridinium Compounds ; }, abstract = {Oxidative stress and neuroinflammation are major contributors to the pathophysiology of ALS. Nicotinamide riboside (a NAD[+] precursor) and pterostilbene (a natural antioxidant) were efficacious in a human pilot study of ALS patients and in ALS SOD1[G93A] transgenic mice. Ibudilast targets different phosphodiesterases and the macrophage migration inhibitory factor, reduces neuroinflammation, and in early-phase studies improved survival and slowed progression in ALS patients. Using two ALS murine models (SOD1[G93A], FUS[R521C]) the effects of nicotinamide riboside, pterostilbene, and ibudilast on disease onset, progression and survival were studied. In both models ibudilast enhanced the effects of nicotinamide riboside and pterostilbene on survival and neuromotor functions. The triple combination reduced microgliosis and astrogliosis, and the levels of different proinflammatory cytokines in the CSF. TNFα, IFNγ and IL1β increased H2O2 and NO generation by motor neurons, astrocytes, microglia and endothelial cells isolated from ALS mice. Nicotinamide riboside and pterostilbene decreased H2O2 and NO generation in all these cells. Ibudilast specifically decreased TNFα levels and H2O2 generation by microglia and endothelial cells. Unexpectedly, pathophysiological concentrations of H2O2 or NO caused minimal motor neuron cytotoxicity. H2O2-induced cytotoxicity was increased by NO via a trace metal-dependent formation of potent oxidants (i.e. OH and [-]OONO radicals). In conclusion, our results show that the combination of nicotinamide riboside, pterostilbene and ibudilast improve neuromotor functions and survival in ALS murine models. Studies on the underlying mechanisms show that motor neuron protection involves the decrease of oxidative and nitrosative stress, the combination of which is highly damaging to motor neurons.}, } @article {pmid38240416, year = {2024}, author = {Schuster, J and Dreyhaupt, J and Mönkemöller, K and Dupuis, L and Dieterlé, S and Weishaupt, JH and Kassubek, J and Petri, S and Meyer, T and Grosskreutz, J and Schrank, B and Boentert, M and Emmer, A and Hermann, A and Zeller, D and Prudlo, J and Winkler, AS and Grehl, T and Heneka, MT and Johannesen, S and Göricke, B and Witzel, S and Dorst, J and Ludolph, AC and , }, title = {In-depth analysis of data from the RAS-ALS study reveals new insights in rasagiline treatment for amyotrophic lateral sclerosis.}, journal = {European journal of neurology}, volume = {31}, number = {4}, pages = {e16204}, pmid = {38240416}, issn = {1468-1331}, support = {//Teva Pharmaceutical Industries/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/complications ; Indans/therapeutic use ; Disease Progression ; }, abstract = {BACKGROUND AND PURPOSE: In 2016, we concluded a randomized controlled trial testing 1 mg rasagiline per day add-on to standard therapy in 252 amyotrophic lateral sclerosis (ALS) patients. This article aims at better characterizing ALS patients who could possibly benefit from rasagiline by reporting new subgroup analysis and genetic data.

METHODS: We performed further exploratory in-depth analyses of the study population and investigated the relevance of single nucleotide polymorphisms (SNPs) related to the dopaminergic system.

RESULTS: Placebo-treated patients with very slow disease progression (loss of Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised [ALSFRS-R] per month before randomization of ≤0.328 points) showed a per se survival probability after 24 months of 0.85 (95% confidence interval = 0.65-0.94). The large group of intermediate to fast progressing ALS patients showed a prolonged survival in the rasagiline group compared to placebo after 6 and 12 months (p = 0.02, p = 0.04), and a reduced decline of ALSFRS-R after 18 months (p = 0.049). SNP genotypes in the MAOB gene and DRD2 gene did not show clear associations with rasagiline treatment effects.

CONCLUSIONS: These results underline the need to consider individual disease progression at baseline in future ALS studies. Very slow disease progressors compromise the statistical power of studies with treatment durations of 12-18 months using clinical endpoints. Analysis of MAOB and DRD2 SNPs revealed no clear relationship to any outcome parameter. More insights are expected from future studies elucidating whether patients with DRD2CC genotype (Rs2283265) show a pronounced benefit from treatment with rasagiline, pointing to the opportunities precision medicine could open up for ALS patients in the future.}, } @article {pmid38240367, year = {2024}, author = {Hobin, F and De Vocht, J and Lamaire, N and Beyens, H and Ombelet, F and Van Damme, P}, title = {Specialized multidisciplinary care improves ALS survival in Belgium: a population-based retrospective study.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {25}, number = {3-4}, pages = {282-289}, doi = {10.1080/21678421.2024.2304058}, pmid = {38240367}, issn = {2167-9223}, mesh = {Humans ; Retrospective Studies ; *Amyotrophic Lateral Sclerosis/diagnosis/epidemiology/therapy ; Belgium/epidemiology ; *Neurodegenerative Diseases ; Prognosis ; }, abstract = {ALS is a neurodegenerative disease characterized by loss of motor neurons, resulting in progressive weakness and wasting of muscles. The average survival time is 2-5 years, mostly due to respiratory failure. Since current therapies can prolong survival time by only a few months, multidisciplinary care remains the cornerstone of the management of ALS. At the ALS Expert Centre of University Hospitals Leuven, a large proportion of Belgian ALS patients are seen for diagnosis and a significant number is also in follow-up with the multidisciplinary team. In this retrospective study, we compared the outcome of incident patients who were in follow-up at our site with patients who were not in follow-up. We included 659 patients of which 557 (84.5%) received specialized care at the ALS Expert Centre. After adjusting for clinically relevant prognostic parameters, multidisciplinary follow-up significantly prolonged survival (p = 0.004; HR = 0.683; CI 95% [0.528 - 0.884]). This increase in survival is mainly driven by patients with spinal onset (p = 0.035; HR = 0.746; CI 95% [0.568 - 0.980]), since no significant increased survival time was observed in patients with bulbar onset (p = 0.28; HR = 0.778; CI 95% [0.495 - 1.223]). These data confirm that multidisciplinary follow-up contributes to a better outcome of patients, emphasizing the importance of multidisciplinary specialized care in ALS.}, } @article {pmid38239833, year = {2023}, author = {Eck, RJ and Stair, JG and Kraemer, BC and Liachko, NF}, title = {Simple models to understand complex disease: 10 years of progress from Caenorhabditis elegans models of amyotrophic lateral sclerosis and frontotemporal lobar degeneration.}, journal = {Frontiers in neuroscience}, volume = {17}, number = {}, pages = {1300705}, pmid = {38239833}, issn = {1662-4548}, support = {P40 OD010440/OD/NIH HHS/United States ; F31 AG082391/AG/NIA NIH HHS/United States ; I01 BX005762/BX/BLRD VA/United States ; I01 BX004044/BX/BLRD VA/United States ; RF1 AG055474/AG/NIA NIH HHS/United States ; T32 GM136534/GM/NIGMS NIH HHS/United States ; I01 BX002619/BX/BLRD VA/United States ; R01 AG066729/AG/NIA NIH HHS/United States ; IK6 BX006467/BX/BLRD VA/United States ; R01 NS064131/NS/NINDS NIH HHS/United States ; }, abstract = {The nematode Caenorhabditis elegans are a powerful model system to study human disease, with numerous experimental advantages including significant genetic and cellular homology to vertebrate animals, a short lifespan, and tractable behavioral, molecular biology and imaging assays. Beginning with the identification of SOD1 as a genetic cause of amyotrophic lateral sclerosis (ALS), C. elegans have contributed to a deeper understanding of the mechanistic underpinnings of this devastating neurodegenerative disease. More recently this work has expanded to encompass models of other types of ALS and the related disease frontotemporal lobar degeneration (FTLD-TDP), including those characterized by mutation or accumulation of the proteins TDP-43, C9orf72, FUS, HnRNPA2B1, ALS2, DCTN1, CHCHD10, ELP3, TUBA4A, CAV1, UBQLN2, ATXN3, TIA1, KIF5A, VAPB, GRN, and RAB38. In this review we summarize these models and the progress and insights from the last ten years of using C. elegans to study the neurodegenerative diseases ALS and FTLD-TDP.}, } @article {pmid38239560, year = {2023}, author = {Wang, G and Jin, S and Liu, J and Li, X and Dai, P and Wang, Y and Hou, SX}, title = {A neuron-immune circuit regulates neurodegeneration in the hindbrain and spinal cord of Arf1-ablated mice.}, journal = {National science review}, volume = {10}, number = {12}, pages = {nwad222}, pmid = {38239560}, issn = {2053-714X}, abstract = {Neuroimmune connections have been revealed to play a central role in neurodegenerative diseases (NDs). However, the mechanisms that link the central nervous system (CNS) and peripheral immune cells are still mostly unknown. We recently found that specific ablation of the Arf1 gene in hindbrain and spinal cord neurons promoted NDs through activating the NLRP3 inflammasome in microglia via peroxided lipids and adenosine triphosphate (ATP) releasing. Here, we demonstrate that IL-1β with elevated chemokines in the neuronal Arf1-ablated mouse hindbrain and spinal cord recruited and activated γδ T cells in meninges. The activated γδ T cells then secreted IFN-γ that entered into parenchyma to activate the microglia-A1 astrocyte-C3-neuronal C3aR neurotoxic pathway. Remarkably, the neurodegenerative phenotypes of the neuronal Arf1-ablated mice were strongly ameliorated by IFN-γ or C3 knockout. Finally, we show that the Arf1-reduction-induced neuroimmune-IFN-γ-gliosis pathway exists in human NDs, particularly in amyotrophic lateral sclerosis and multiple sclerosis. Together, our results uncover a previously unknown mechanism that links the CNS and peripheral immune cells to promote neurodegeneration.}, } @article {pmid38239315, year = {2024}, author = {Kim, K and Ko, DS and Kim, JW and Lee, D and Son, E and Kim, HW and Song, TJ and Kim, YH}, title = {Association of smoking with amyotrophic lateral sclerosis: A systematic review, meta-analysis, and dose-response analysis.}, journal = {Tobacco induced diseases}, volume = {22}, number = {}, pages = {}, pmid = {38239315}, issn = {1617-9625}, abstract = {INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder primarily affecting the voluntary motor nervous system. Several observational studies have provided conflicting results regarding the association between smoking and ALS. Therefore, our objective was to investigate this association through a systematic review, meta-analysis, and dose-response analysis.

METHODS: On 16 January 2023, we initially extracted records from medical databases, which included Medline, Embase, Web of Science, Scopus, and ScienceDirect. We included case-control and cohort studies as eligible studies. Subgroup analyses were performed based on sex, study design, and current smoking. Restricted cubic-spline analysis was utilized to assess the dose-response relationship between smoking (pack-years) and ALS.

RESULTS: Twenty-eight case-control and four cohort studies met the inclusion criteria. The unadjusted OR for the overall association between smoking and ALS was 1.14 (95% CI: 1.06-1.22, I[2]=44%, p<0.001), and the adjusted OR (AOR) was 1.12 (95% CI: 1.03-1.21, I[2]=49%, p=0.009). Subgroup analysis revealed a more pronounced association among current smokers, with an AOR of 1.28 (95% CI: 1.10-1.49, I[2]=66%, p<0.001) and AOR of 1.28 (95% CI: 1.10-1.48, I[2]=58%, p=0.001). In the dose-response analysis, the non-linear model revealed an inverted U-shaped curve.

CONCLUSIONS: Our study provides evidence of a positive relationship between smoking and the risk of ALS. To mitigate the risk of developing ALS, discontinuing smoking, which is a modifiable risk factor, may be crucial.TRIAL REGISTRATION: The study was registered in PROSPERO.IDENTIFIER: CRD42023388822.}, } @article {pmid38239147, year = {2024}, author = {Lin, J and Wang, J and Wang, C and Shan, Y and Jing, W and Fei, Z and Pan, W}, title = {Network pharmacology analysis and clinical efficacy of the traditional Chinese medicine Bu-Shen-Jian-Pi. Part 1: Biogenic components and identification of targets and signaling pathways in amyotrophic lateral sclerosis patients.}, journal = {International journal of clinical pharmacology and therapeutics}, volume = {62}, number = {4}, pages = {155-161}, doi = {10.5414/CP204501}, pmid = {38239147}, issn = {0946-1965}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy ; Medicine, Chinese Traditional ; Network Pharmacology ; Treatment Outcome ; Busulfan ; Signal Transduction ; Molecular Docking Simulation ; *Drugs, Chinese Herbal/pharmacology/therapeutic use ; }, abstract = {BACKGROUND: There is evidence that Bu-Shen-Jian-Pi (BSJP), a traditional Chinese medicine, has curative effects in patients suffering from amyotrophic lateral sclerosis (ALS), a progressive and potentially fatal hypoxic condition.

OBJECTIVE: To identify biogenic components in BSJP extracts having potential pharmacological efficacy in ALS.

MATERIALS AND METHODS: Biogenic components in BSJP and their potential pharmacological targets and signaling pathways in ALS were identified and assessed using network pharmacology/hub node analysis.

RESULTS: Network pharmacology analysis identified icariin, naringenin, kaempferol, quercetin, and formononetin as core components in BSJP with potential activity involving mitochondrial protection in patients with ALS.

CONCLUSION: Network pharmacology analysis proved to be a successful screening tool for obtaining information from scientific databases on the pharmacology of biogenic components in BSJP showing potential therapeutic activity in ALS.}, } @article {pmid38238759, year = {2024}, author = {Séguin, P and Maby, E and Fouillen, M and Otman, A and Luauté, J and Giraux, P and Morlet, D and Mattout, J}, title = {The challenge of controlling an auditory BCI in the case of severe motor disability.}, journal = {Journal of neuroengineering and rehabilitation}, volume = {21}, number = {1}, pages = {9}, pmid = {38238759}, issn = {1743-0003}, support = {DEA20140629858//Fondation pour la Recherche Médicale/ ; ING20121226307//Fondation pour la Recherche Médicale/ ; ANR-17-CE40-0005//Agence Nationale de la Recherche/ ; Labex Cortex (ANR-11-LABX-0042)//Agence Nationale de la Recherche/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis ; *Brain-Computer Interfaces ; *Persons with Disabilities ; Electroencephalography ; *Locked-In Syndrome ; *Motor Disorders ; }, abstract = {BACKGROUND: The locked-in syndrome (LIS), due to a lesion in the pons, impedes communication. This situation can also be met after some severe brain injury or in advanced Amyotrophic Lateral Sclerosis (ALS). In the most severe condition, the persons cannot communicate at all because of a complete oculomotor paralysis (Complete LIS or CLIS). This even prevents the detection of consciousness. Some studies suggest that auditory brain-computer interface (BCI) could restore a communication through a « yes-no» code.

METHODS: We developed an auditory EEG-based interface which makes use of voluntary modulations of attention, to restore a yes-no communication code in non-responding persons. This binary BCI uses repeated speech sounds (alternating "yes" on the right ear and "no" on the left ear) corresponding to either frequent (short) or rare (long) stimuli. Users are instructed to pay attention to the relevant stimuli only. We tested this BCI with 18 healthy subjects, and 7 people with severe motor disability (3 "classical" persons with locked-in syndrome and 4 persons with ALS).

RESULTS: We report online BCI performance and offline event-related potential analysis. On average in healthy subjects, online BCI accuracy reached 86% based on 50 questions. Only one out of 18 subjects could not perform above chance level. Ten subjects had an accuracy above 90%. However, most patients could not produce online performance above chance level, except for two people with ALS who obtained 100% accuracy. We report individual event-related potentials and their modulation by attention. In addition to the classical P3b, we observed a signature of sustained attention on responses to frequent sounds, but in healthy subjects and patients with good BCI control only.

CONCLUSIONS: Auditory BCI can be very well controlled by healthy subjects, but it is not a guarantee that it can be readily used by the target population of persons in LIS or CLIS. A conclusion that is supported by a few previous findings in BCI and should now trigger research to assess the reasons of such a gap in order to propose new and efficient solutions.

CLINICAL TRIAL REGISTRATIONS: No. NCT02567201 (2015) and NCT03233282 (2013).}, } @article {pmid38237070, year = {2024}, author = {Goto, S and Maeda, N and Ohnuma, K and Lawu, T and Ogawa, K and Sugiyama, S and Matsumaru, M and Noda, T}, title = {Impact of segmented optical axial length on the performance of intraocular lens power calculation formulas.}, journal = {Journal of cataract and refractive surgery}, volume = {50}, number = {5}, pages = {492-497}, doi = {10.1097/j.jcrs.0000000000001397}, pmid = {38237070}, issn = {1873-4502}, mesh = {Humans ; *Axial Length, Eye/pathology/diagnostic imaging ; *Lenses, Intraocular ; Retrospective Studies ; *Biometry/methods ; *Optics and Photonics ; Male ; Female ; *Tomography, Optical Coherence/methods ; *Phacoemulsification ; *Refraction, Ocular/physiology ; Lens Implantation, Intraocular ; Aged ; Middle Aged ; Aged, 80 and over ; Visual Acuity/physiology ; Pseudophakia/physiopathology ; }, abstract = {PURPOSE: To investigate the difference between the segmented axial length (AL) and the composite AL on a swept-source optical coherence tomography biometer and to evaluate the subsequent effects on artificial intelligence intraocular lens (IOL) power calculations: the Kane and Hill-RBF 3.0 formulas compared with established vergence formulas.

SETTING: National Hospital Organization, Tokyo Medical Center, Japan.

DESIGN: Retrospective case series.

METHODS: Consecutive patients undergoing cataract surgery with a single-piece IOL were reviewed. The prediction accuracy of the Barrett Universal II, Haigis, Hill-RBF 3.0, Hoffer Q, Holladay 1, Kane, and SRK/T formulas based on 2 ALs were compared for each formula. The heteroscedastic test was used with the SD of prediction errors as the endpoint for formula performance.

RESULTS: The study included 145 eyes of 145 patients. The segmented AL (24.83 ± 1.89) was significantly shorter than the composite AL (24.88 ± 1.96, P < .001). Bland-Altman analysis revealed a negative proportional bias for the differences between the segmented AL and the composite AL. The SD values obtained by Hoffer Q, Holladay 1, and SRK/T formulas based on the segmented AL (0.52 diopters [D], 0.54 D, and 0.50 D, respectively) were significantly lower than those based on the composite AL (0.57 D, 0.60 D, and 0.52 D, respectively, P < .01).

CONCLUSIONS: The segmented ALs were longer in short eyes and shorter in long eyes than the composite ALs. The refractive accuracy can be improved in the Hoffer Q, Holladay 1, and SRK/T formulas by changing the composite ALs to the segmented ALs.}, } @article {pmid38236205, year = {2024}, author = {Bryson, JB and Kourgiantaki, A and Jiang, D and Demosthenous, A and Greensmith, L}, title = {An optogenetic cell therapy to restore control of target muscles in an aggressive mouse model of amyotrophic lateral sclerosis.}, journal = {eLife}, volume = {12}, number = {}, pages = {}, pmid = {38236205}, issn = {2050-084X}, support = {Bryson 965-799/MNDA_/Motor Neurone Disease Association/United Kingdom ; MR/R011648/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Animals ; Mice ; Humans ; *Amyotrophic Lateral Sclerosis/genetics/therapy ; Optogenetics ; Muscle, Skeletal ; Paralysis ; Cell- and Tissue-Based Therapy ; Disease Models, Animal ; }, abstract = {Breakdown of neuromuscular junctions (NMJs) is an early pathological hallmark of amyotrophic lateral sclerosis (ALS) that blocks neuromuscular transmission, leading to muscle weakness, paralysis and, ultimately, premature death. Currently, no therapies exist that can prevent progressive motor neuron degeneration, muscle denervation, or paralysis in ALS. Here, we report important advances in the development of an optogenetic, neural replacement strategy that can effectively restore innervation of severely affected skeletal muscles in the aggressive SOD1[G93A] mouse model of ALS, thus providing an interface to selectively control the function of targeted muscles using optical stimulation. We also identify a specific approach to confer complete survival of allogeneic replacement motor neurons. Furthermore, we demonstrate that an optical stimulation training paradigm can prevent atrophy of reinnervated muscle fibers and results in a tenfold increase in optically evoked contractile force. Together, these advances pave the way for an assistive therapy that could benefit all ALS patients.}, } @article {pmid38235854, year = {2024}, author = {Dukic, S and Fasano, A and Coffey, A and Buxó, T and McMackin, R and Chipika, R and Heverin, M and Bede, P and Muthuraman, M and Lowery, M and Carson, RG and Hardiman, O and Nasseroleslami, B}, title = {Electroencephalographic β-band oscillations in the sensorimotor network reflect motor symptom severity in amyotrophic lateral sclerosis.}, journal = {European journal of neurology}, volume = {31}, number = {4}, pages = {e16201}, pmid = {38235854}, issn = {1468-1331}, support = {/WT_/Wellcome Trust/United Kingdom ; 16/ERCD/3854/SFI_/Science Foundation Ireland/Ireland ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis ; Electroencephalography ; Motor Neurons ; Brain ; Brain Mapping ; }, abstract = {BACKGROUND AND PURPOSE: Resting-state electroencephalography (EEG) holds promise for assessing brain networks in amyotrophic lateral sclerosis (ALS). We investigated whether neural β-band oscillations in the sensorimotor network could serve as an objective quantitative measure of progressive motor impairment and functional disability in ALS patients.

METHODS: Resting-state EEG was recorded in 18 people with ALS and 38 age- and gender-matched healthy controls. We estimated source-localized β-band spectral power in the sensorimotor cortex. Clinical evaluation included lower (LMN) and upper motor neuron scores, Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised score, fine motor function (FMF) subscore, and progression rate. Correlations between clinical scores and β-band power were analysed and corrected using a false discovery rate of q = 0.05.

RESULTS: β-Band power was significantly lower in people with ALS than controls (p = 0.004), and correlated with LMN score (R = -0.65, p = 0.013), FMF subscore (R = -0.53, p = 0.036), and FMF progression rate (R = 0.52, p = 0.036).

CONCLUSIONS: β-Band spectral power in the sensorimotor cortex reflects clinically evaluated motor impairment in ALS. This technology merits further investigation as a biomarker of progressive functional disability.}, } @article {pmid38235844, year = {2024}, author = {Zhang, L and Li, Y and Niu, J and Hu, N and Ding, J and Cui, L and Liu, M}, title = {Neuromuscular ultrasound in combination with nerve conduction studies helps identify inflammatory motor neuropathies from lower motor neuron syndromes.}, journal = {European journal of neurology}, volume = {31}, number = {4}, pages = {e16202}, pmid = {38235844}, issn = {1468-1331}, support = {CIFMS 2021-I2M-1-003//CAMS Innovation Fund for Medical Sciences/ ; 2022-PUMCH-B-017//National High Level Hospital Clinical Research Funding/ ; 2016YFC0905103//National Key Research and Development Program of China/ ; grant XDB39040000//the Strategic Priority Research Program (Pilot study) "Biological basis of aging and therapeutic strategies" of the Chinese Academy of Sciences/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis ; *Polyradiculoneuropathy, Chronic Inflammatory Demyelinating/therapy ; Nerve Conduction Studies ; Neural Conduction/physiology ; Motor Neurons ; *Polyneuropathies ; *Motor Neuron Disease ; }, abstract = {BACKGROUND AND PURPOSE: Identifying patients with inflammatory motor neuropathies (IMNs) is warranted since effective treatments are available and the prognosis of these patients differs from that of amyotrophic lateral sclerosis patients.

METHODS: Between January 2019 and May 2022, 102 consecutive treatment-naïve lower motor neuron syndrome (LMNS) patients were recruited; these patients were suspected of having multifocal motor neuropathy, pure motor chronic inflammatory demyelinating polyneuropathy or amyotrophic lateral sclerosis with initial lower motor neuron presentation. Neuromuscular ultrasound (US) and nerve conduction studies (NCSs) were conducted at baseline. Relevant diagnostic investigations were performed if clinically warranted. The proposed US evidence of IMN was as follows: (i) nerve enlargement at ≥1 of the predetermined sites or (ii) absence of high intensity fasciculations in predefined muscle groups. Final diagnoses were made by experienced physicians after a prolonged follow-up period (≥12 months). IMN patients were defined as LMNS patients who experienced convincing improvements in response to immunotherapies. IMN patients without electrodiagnostic demyelinating features were diagnosed with treatment-responsive LMNS (TR-LMNS).

RESULTS: In total, 16 patients were classified as IMN, including nine chronic inflammatory demyelinating polyneuropathy/multifocal motor neuropathy patients and seven TR-LMNS patients. Six TR-LMNS patients were identified by neuromuscular US. The sensitivity and specificity of NCSs, nerve US and muscle US were 56.3% and 100%, 43.8% and 90.7% and 68.8% and 97.7%, respectively. When these three modalities were combined, the sensitivity and specificity were 93.8% and 88.4%, respectively.

CONCLUSION: Neuromuscular US studies are supplementary modalities to NCSs, and the combined use of these techniques might improve the identification of IMNs in LMNS patients.}, } @article {pmid38235589, year = {2024}, author = {Gebrehiwet, P and Aggarwal, S and Topaloglu, O and Chiò, A}, title = {Feasibility assessment of using the MiToS staging system for conducting economic evaluation in amyotrophic lateral sclerosis.}, journal = {Expert review of pharmacoeconomics & outcomes research}, volume = {24}, number = {3}, pages = {447-458}, doi = {10.1080/14737167.2024.2306819}, pmid = {38235589}, issn = {1744-8379}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy ; Cost-Benefit Analysis ; Feasibility Studies ; Mitochondria Associated Membranes ; Disease Progression ; Quality-Adjusted Life Years ; }, abstract = {OBJECTIVES: This study assessed the feasibility of using the Milano-Torino staging (MiToS) system for conducting economic evaluation to measure health outcomes in amyotrophic lateral sclerosis (ALS).

METHODS: A Markov model was developed using the MiToS system and evaluated with a hypothetical treatment versus standard of care. Health utilities and transition probabilities were derived from the literature. Four-time horizons (1, 5, 10, and 20 years) were examined. Treatment effects of 20-35% relative risk reduction (RRR) of progressing to the next MiToS stage were assessed. Three patient distribution scenarios were tested: (1) all patients began in stage 0; (2) patient distribution based on real-world TONiC study; (3) distribution based on the PRO-ACT database. Health outcomes (quality-adjusted life-years [QALYs], life-years [LYs]) were reported with a 3% discount rate.

RESULTS: A time horizon of 10 years fully captured treatment benefits: incremental QALYs were 0.28-0.60, 0.21-0.45, and 0.26-0.55 for scenarios 1-3, respectively; incremental LYs were 0.56-1.17, 0.46-0.97, and 0.53-1.11, respectively.

CONCLUSION: MiToS-based staging can be used for conducting economic analyses in ALS. Estimated incremental QALY and LY gains were meaningful within the context of ALS, for hypothetical treatments with RRR of 20-35%.}, } @article {pmid38234062, year = {2024}, author = {Stanziano, M and Fedeli, D and Manera, U and Ferraro, S and Medina Carrion, JP and Palermo, S and Sciortino, P and Cogoni, M and Agosta, F and Basaia, S and Filippi, M and Grisoli, M and Valentini, MC and De Mattei, F and Canosa, A and Calvo, A and Bruzzone, MG and Chiò, A and Nigri, A and Moglia, C}, title = {Resting-state fMRI functional connectome of C9orf72 mutation status.}, journal = {Annals of clinical and translational neurology}, volume = {11}, number = {3}, pages = {686-697}, pmid = {38234062}, issn = {2328-9503}, support = {GR-2019-12371291//Italian Ministry of Health/ ; RF-2016-02362405//Italian Ministry of Health/ ; RRC//Italian Ministry of Health/ ; //Ministero della Salute/ ; //Ricerca Sanitaria Finalizzata/ ; //Giovani ricercatori/ ; 259867//European Commission's Health Seventh Framework Programme/ ; //Italian Ministry of Education, University and Research/ ; 2017SNW5MB//Progetti di Ricerca di Rilevante Interesse Nazionale, PRIN/ ; //Joint Programme - Neurodegenerative Disease Research/ ; //Department of Excellence/ ; //'Rita Levi Montalcini' Department of Neuroscience/ ; //University of Torino, Italy/ ; }, mesh = {Humans ; Magnetic Resonance Imaging ; *Amyotrophic Lateral Sclerosis/diagnostic imaging/genetics/pathology ; C9orf72 Protein/genetics ; *Connectome ; DNA Repeat Expansion/genetics ; Proteins/genetics ; Mutation ; }, abstract = {OBJECTIVE: The resting-state functional connectome has not been extensively investigated in amyotrophic lateral sclerosis (ALS) spectrum disease, in particular in relationship with patients' genetic status.

METHODS: Here we studied the network-to-network connectivity of 19 ALS patients carrying the C9orf72 hexanucleotide repeat expansion (C9orf72+), 19 ALS patients not affected by C9orf72 mutation (C9orf72-), and 19 ALS-mimic patients (ALSm) well-matched for demographic and clinical variables.

RESULTS: When compared with ALSm, we observed greater connectivity of the default mode and frontoparietal networks with the visual network for C9orf72+ patients (P = 0.001). Moreover, the whole-connectome showed greater node degree (P < 0.001), while sensorimotor cortices resulted isolated in C9orf72+.

INTERPRETATION: Our results suggest a crucial involvement of extra-motor functions in ALS spectrum disease. In particular, alterations of the visual cortex may have a pathogenic role in C9orf72-related ALS. The prominent feature of these patients would be increased visual system connectivity with the networks responsible of the functional balance between internal and external attention.}, } @article {pmid38233111, year = {2025}, author = {Kunji Koya, R and Branston, JR and Gallagher, AWA and Bui, WKT and Ross, H and Mohamed Nor, N}, title = {Improving estimates of the illicit cigarette trade through collaboration: lessons from two studies of Malaysia.}, journal = {Tobacco control}, volume = {34}, number = {2}, pages = {242-247}, pmid = {38233111}, issn = {1468-3318}, mesh = {Malaysia ; *Tobacco Products/economics/statistics & numerical data ; Humans ; *Commerce/statistics & numerical data/economics ; *Taxes/statistics & numerical data ; *Crime/statistics & numerical data ; Cooperative Behavior ; }, abstract = {This paper critically analyses contrasting estimates of Malaysia's illicit cigarette trade in 2011, 2015 and 2019 by Bui et al and Koya et al who previously produced independent estimates at about the same time using tax gap analysis. Collaboration between the two authors' teams emerged due to the discrepancies in their results, generating this paper to explore the methodological issues identified and hence produce revised estimates of the rate of illicit. Key issues identified were: Bui et al's assessment of legally imported cigarettes impacting all years; their exclusion of ad valorem duty affecting the 2011 and 2015 estimates; Koya et al overlooked the value of cigarettes for export market in their ad valorem calculation and used the sales value of imported tobacco/tobacco products, not just cigarettes, both of which impact estimates for 2011 and 2015. Recalculations using Koya et al's consumption data reveal that in 2019, illicit cigarettes accounted for about 70% of the market, which is higher than Bui et al's estimate (38%) but slightly lower than Koya et al's (72%). For 2011 and 2015 where ad valorem applied, the corrected estimates show a share of the illicit cigarette market of approximately 41.1% and 52.7%, respectively, differing from Bui et al's 0% in 2011 and 29.6% in 2015, and Koya et al's 51% in 2011 and 55% in 2015. This paper provides essential lessons for addressing methodological issues between authors' teams and updated estimates of Malaysia's illicit cigarette trade, verifying that Malaysia faces a substantial illicit cigarette trade problem.}, } @article {pmid38229740, year = {2024}, author = {Rosse, G}, title = {Novel Pyrazolopyridine Inhibitors of Monoacylglycerol Lipase for the Treatment of Neurodegenerative Diseases and Neuroinflammation.}, journal = {ACS medicinal chemistry letters}, volume = {15}, number = {1}, pages = {19-20}, pmid = {38229740}, issn = {1948-5875}, abstract = {This work highlights the use of bicyclic heterocyclic compounds as monoacylglycerol lipase inhibitors potentially in the treatment of Alzheimer's disease, Parkinson's disease, ALS, traumatic brain injury, and multiple sclerosis.}, } @article {pmid38229533, year = {2024}, author = {Feng, Y and Xu, Z and Jin, H and Chen, Y and Fu, C and Zhang, Y and Yin, Y and Wang, H and Cheng, W}, title = {Metformin ameliorates mitochondrial damage induced by C9orf72 poly(GR) via upregulating AKT phosphorylation.}, journal = {Journal of cellular biochemistry}, volume = {125}, number = {3}, pages = {e30526}, doi = {10.1002/jcb.30526}, pmid = {38229533}, issn = {1097-4644}, support = {23ZR1441200//Natural Science Foundation of Shanghai/ ; 20QA1406300//Shanghai Rising-Star Program/ ; 81901162//National Natural Science Foundation of China/ ; 81974270//National Natural Science Foundation of China/ ; }, mesh = {Humans ; *Frontotemporal Dementia/drug therapy/genetics/metabolism ; *Amyotrophic Lateral Sclerosis/drug therapy/genetics ; Proto-Oncogene Proteins c-akt/genetics/metabolism ; C9orf72 Protein/genetics/metabolism ; Phosphorylation ; Dipeptides ; }, abstract = {Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are devastating neurodegenerative diseases with no effective cure. GGGGCC repeat expansion in C9orf72 is the most common genetic cause of both ALS and FTD. A key pathological feature of C9orf72 related ALS/FTD is the presence of abnormal dipeptide repeat proteins translated from GGGGCC repeat expansion, including poly Glycine-Arginine (GR). In this study, we observed that (GR)50 conferred significant mitochondria damage and cytotoxicity. Metformin, the most widely used clinical drug, successfully relieved (GR)50 induced mitochondrial damage and inhibited (GR)50 related cytotoxicity. Further research revealed metformin effectively restored mitochondrial function by upregulating AKT phosphorylation in (GR)50 expressed cells. Taken together, our results indicated restoring mitochondrial function with metformin may be a rational therapeutic strategy to reduce poly(GR) toxicity in C9orf72 ALS/FTD patients.}, } @article {pmid38229194, year = {2024}, author = {Jadhav, PA and Hole, A and Ingle, A and Govekar, R and Noothalapati, H and Krishna, CM}, title = {Serum Raman spectroscopy: Evaluation of tumour load variations in experimental carcinogenesis.}, journal = {Journal of biophotonics}, volume = {17}, number = {4}, pages = {e202300424}, doi = {10.1002/jbio.202300424}, pmid = {38229194}, issn = {1864-0648}, mesh = {Animals ; Cricetinae ; Humans ; *Spectrum Analysis, Raman/methods ; Tumor Burden ; Multivariate Analysis ; Discriminant Analysis ; *Cell Transformation, Neoplastic ; Least-Squares Analysis ; }, abstract = {Several serum Raman spectroscopy (RS) studies have demonstrated its potential as an oral cancer screening tool. This study investigates influence of low tumour load (LTL) and high tumour load (HTL) on serum RS using hamster buccal pouch model of experimental oral carcinogenesis. Sera of untreated control, LTL, and HTL groups at week intervals during malignant transformation were employed. Serum Raman spectra were subjected to multivariate analyses-principal component analysis, principal component-based linear discriminant analysis (for stratification of study groups), and multivariate curve resolution-alternating least squares (MCR-ALS) (to comprehend biomolecular differences). Multivariate analysis revealed misclassifications between LTL and HTL at all week intervals. MCR-ALS components showed statistically significant abundances between control versus LTL and control versus HTL, but could not discern LTL and HTL. MCR-ALS components exhibited spectral mixtures of proteins, lipids, heme and nucleic acids. Thus, these findings support use of serum RS as a screening tool as varying tumour load is not a confounding factor influencing the technique.}, } @article {pmid38227807, year = {2024}, author = {Carbayo, Á and Borrego-Écija, S and Turon-Sans, J and Cortés-Vicente, E and Molina-Porcel, L and Gascón-Bayarri, J and Rubio, MÁ and Povedano, M and Gámez, J and Sotoca, J and Juntas-Morales, R and Almendrote, M and Marquié, M and Sánchez-Valle, R and Illán-Gala, I and Dols-Icardo, O and Rubio-Guerra, S and Bernal, S and Caballero-Ávila, M and Vesperinas, A and Gelpi, E and Rojas-García, R}, title = {Clinicopathological correlates in the frontotemporal lobar degeneration-motor neuron disease spectrum.}, journal = {Brain : a journal of neurology}, volume = {147}, number = {7}, pages = {2357-2367}, pmid = {38227807}, issn = {1460-2156}, support = {CM21/00057//Río Hortega Contract/ ; //Instituto de Salud Carlos III/ ; //Atlantic Fellow for Equity in Brain Health/ ; //Global Brain Health Institute/ ; /ALZ/Alzheimer's Association/United States ; ALZ UK-21-720973/ALZS_/Alzheimer's Society/United Kingdom ; JR20/0018//Juan Rodés Contract/ ; JR19/00037//Juan Rodés Contract/ ; }, mesh = {Humans ; Male ; Female ; Aged ; Middle Aged ; *Frontotemporal Lobar Degeneration/pathology/genetics ; Retrospective Studies ; *Motor Neuron Disease/pathology/genetics ; Amyotrophic Lateral Sclerosis/pathology/genetics ; Frontotemporal Dementia/pathology/genetics ; Brain/pathology ; DNA-Binding Proteins/genetics/metabolism ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a devastating motor neuron disease (MND) that shares a common clinical, genetic and pathologic spectrum with frontotemporal dementia (FTD). It is highly heterogeneous in its presentation and features. Up to 50% of patients with MND develop cognitive-behavioural symptoms during the course of the disease, meeting criteria for FTD in 10%-15% of cases. In the absence of a precise biomarker, neuropathology is still a valuable tool to understand disease nosology, reach a definite diagnostic confirmation and help define specific subgroups of patients with common phenotypic, genetic and biomarker profiles. However, few neuropathological series have been published, and the frequency of frontotemporal lobar degeneration (FTLD) in MND is difficult to estimate. In this work we describe a large clinicopathological series of MND patients, analysing the frequency of concurrent FTLD changes and trying to define specific subgroups of patients based on their clinical, genetic and pathological characteristics. We performed an observational, retrospective, multicentre case study. We included all cases meeting neuropathological criteria for MND from the Neurological Tissue Bank of the FRCB-IDIBAPS-Hospital Clínic Barcelona Biobank between 1994 and 2022, regardless of their last clinical diagnosis. While brain donation is encouraged in all patients, it is performed in very few, and representativeness of the cohort might not be precise for all patients with MND. We retrospectively reviewed clinical and neuropathological data and describe the main clinical, genetic and pathogenic features, comparing neuropathologic groups between MND with and without FTLD changes and aiming to define specific subgroups. We included brain samples from 124 patients, 44 of whom (35.5%) had FTLD neuropathologic features (i.e. FTLD-MND). Pathologic TDP-43 aggregates were present in 93.6% of the cohort and were more extensive (higher Brettschneider stage) in those with concurrent FTLD (P < 0.001). Motor symptom onset was more frequent in the bulbar region in FTLD-MND cases than in those with isolated MND (P = 0.023), with no differences in survival. We observed a better clinicopathological correlation in the MND group than in the FTLD-MND group (93.8% versus 61.4%; P < 0.001). Pathogenic genetic variants were more common in the FTLD-MND group, especially C9orf72. We describe a frequency of FTLD of 35.5% in our series of neuropathologically confirmed cases of MND. The FTLD-MND spectrum is highly heterogeneous in all aspects, especially in patients with FTLD, in whom it is particularly difficult to define specific subgroups. In the absence of definite biomarkers, neuropathology remains a valuable tool for a definite diagnosis, increasing our knowledge in disease nosology.}, } @article {pmid38227505, year = {2024}, author = {Goswami, A and Carra, S}, title = {PML nuclear bodies: new players in familial amyotrophic lateral sclerosis-frontotemporal dementia?.}, journal = {Neural regeneration research}, volume = {19}, number = {9}, pages = {1875-1876}, pmid = {38227505}, issn = {1673-5374}, } @article {pmid38226616, year = {2024}, author = {Otani, R and Shibuya, K and Shimizu, T and Kitaoji, T and Noto, YI and Bokuda, K and Kimura, H and Suichi, T and Nakamura, K and Kano, H and Morooka, M and Aotsuka, Y and Ogushi, M and Misawa, S and Kuwabara, S}, title = {Diagnostic utility of Gold Coast criteria for amyotrophic lateral sclerosis in Asia.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {25}, number = {3-4}, pages = {264-270}, doi = {10.1080/21678421.2024.2303062}, pmid = {38226616}, issn = {2167-9223}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/epidemiology ; Asia ; Electromyography ; Sensitivity and Specificity ; }, abstract = {Objective: This study aimed to reveal the diagnostic utility of Gold Coast (GC) criteria in Japanese patients with amyotrophic lateral sclerosis (ALS) by comparing the sensitivity/specificity with revised El Escorial (R-EE) and Awaji criteria, because its utility has not been studied in Asian ALS. Methods: Consecutive 639 patients (529 with ALS and 110 with ALS mimics), who were suspected of ALS and referred to three Japanese ALS centers, were enrolled. Diagnostic accuracy and characteristics of false positive and negative in GC criteria were compared with those of the Awaji and R-EE criteria. Patients were categorized as definite, probable or possible ALS according to each criterion. Results: The sensitivity of GC criteria (96.8%, 95% confidence interval [CI]: 95.3-98.3%) was higher than that of Awaji (89.6%, 95% CI: 87.0-92.2%) and R-EEC (89.2, 95% CI: 86.6-91.8%) criteria (both, p < 0.001). The specificity was also higher with GC criteria (77.3%, 95% CI: 69.5-85.1%) than Awaji (65.5%, 95% CI: 56.6-74.4%) and R-EEC (66.4, 95% CI: 57.6-75.2%) criteria (both, p < 0.01). Using GC criteria, patients with cervical spondylosis and Parkinson's syndrome tended to be diagnosed with ALS (i.e. "false positive"). Additionally, ALS patients diagnosed only by GC criteria less frequently had upper motor neuron (UMN) signs, compared with the other two criteria. Conclusion: Gold Coast criteria improve diagnostic accuracy for ALS in an Asian population, especially in patients with subtle UMN signs.}, } @article {pmid38226245, year = {2024}, author = {Sharma, S and Mehan, S and Khan, Z and Gupta, GD and Narula, AS}, title = {Icariin prevents methylmercury-induced experimental neurotoxicity: Evidence from cerebrospinal fluid, blood plasma, brain samples, and in-silico investigations.}, journal = {Heliyon}, volume = {10}, number = {1}, pages = {e24050}, pmid = {38226245}, issn = {2405-8440}, abstract = {Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease that causes significant neurodegeneration. Methylmercury (MeHg+) is a neurotoxin that induces axonal neurodegeneration and motor nerve degeneration by destroying oligodendrocytes, degenerating white matter, inducing apoptosis, excitotoxicity, and reducing myelin basic protein (MBP). This study examines the inhibition of SIRT-1 (silence information regulator 1), Nrf-2 (nuclear factor E2-related factor 2), HO-1 (heme oxygenase 1), and TDP-43 (TAR-DNA-binding protein 43) accumulation in the context of ALS, as well as the modulation of these proteins by icariin (15 and 30 mg/kg, orally), a glycoside flavonoid with neuroprotective properties. Neuroprotective icariin activates SIRT-1, Nrf-2, and HO-1, mitigating inflammation and neuronal injury in neurodegenerative disorders. In-vivo and in-silico testing of experimental ALS models confirmed icariin efficacy in modulating these cellular targets. The addition of sirtinol 10 mg/kg, an inhibitor of SIRT-1, helps determine the effectiveness of icariin. In this study, we also examined neurobehavioral, neurochemical, histopathological, and LFB (Luxol fast blue) markers in various biological samples, including Cerebrospinal fluid (CSF), blood plasma, and brain homogenates (Cerebral Cortex, Hippocampus, Striatum, mid-brain, and Cerebellum). These results demonstrate that the administration of icariin ameliorates experimental ALS and that the mechanism underlying these benefits is likely related to regulating the SIRT-1, Nrf-2, and HO-1 signaling pathways.}, } @article {pmid38226086, year = {2023}, author = {AlMadan, N and AlMajed, A and AlAbbad, M and AlNashmi, F and Aleissa, A}, title = {Dental Management of Patients With Amyotrophic Lateral Sclerosis.}, journal = {Cureus}, volume = {15}, number = {12}, pages = {e50602}, pmid = {38226086}, issn = {2168-8184}, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that affects the upper and lower motor neurons with upper and lower motor neuron manifestations. It is divided into two variants: a spinal onset and a bulbar onset. The first starts as focal muscle weakness and wasting that spreads with disease progression, while the second phenotype presents with dysarthria, dysphonia, and dysphagia. Moreover, an extra-motor manifestation could be reported with the most commonly reported symptoms being the change in cognition and sleep disorder. Oral manifestations include increased salivation, limited mouth opening, and dysphagia. Patients with ALS have difficulty maintaining oral hygiene, and it is important for the practitioner and the caregiver to take care of this group of population. We herein provide a short review of the disease with a focus on the oral manifestations and dental considerations for management for this group.}, } @article {pmid38226024, year = {2024}, author = {de Jongh, CA and Bikker, FJ and de Vries, TJ and Werner, A and Gibbs, S and Krom, BP}, title = {Porphyromonas gingivalis interaction with Candida albicans allows for aerobic escape, virulence and adherence.}, journal = {Biofilm}, volume = {7}, number = {}, pages = {100172}, pmid = {38226024}, issn = {2590-2075}, abstract = {In the oral cavity Candida albicans interacts with many oral bacteria, including Porphyromonas gingivalis, both physically and metabolically. The aim of this in vitro study was to characterize these interactions and study their effects on the survival of P. gingivalis. First, metabolic interactions were evaluated by counting the colony forming units (CFU) after co-culturing. The results indicated that the anaerobic bacterium P. gingivalis survives under aerobic conditions when co-cultured with C. albicans. This is due to the oxygen consumption by C. albicans as determined by a reduction in survival upon the addition of Antimycin A. By measuring the protease activity, it was found that the presence of C. albicans induced gingipain activity by P. gingivalis, which is an important virulence factor. Adherence of P. gingivalis to hyphae of C. albicans was observed with a dynamic flow system. Using various C. albicans mutants, it was shown that the mechanism of adhesion was mediated by the cell wall adhesins, members of the agglutinin-like sequence (Als) family: Als3 and Als1. Furthermore, the two microorganisms could be co-cultured into forming a biofilm in which P. gingivalis can survive under aerobic culturing conditions, which was imaged using scanning electron microscopy. This study has further elucidated mechanisms of interaction, virulence acquisition and survival of P. gingivalis when co-cultured with C. albicans. Such survival could be essential for the pathogenicity of P. gingivalis in the oxygen-rich niches of the oral cavity. This study has emphasized the importance of interaction between different microbes in promoting survival, virulence and attachment of pathogens, which could be essential in facilitating penetration into the environment of the host.}, } @article {pmid38225089, year = {2024}, author = {Unan, R and Azapoglu, O and Deligoz, İ and Mennan, H and Al-Khatib, K}, title = {Gene flow and spontaneous mutations are responsible for imidazolinone herbicide-resistant weedy rice (Oryza sativa L.).}, journal = {Pesticide biochemistry and physiology}, volume = {198}, number = {}, pages = {105746}, doi = {10.1016/j.pestbp.2023.105746}, pmid = {38225089}, issn = {1095-9939}, mesh = {*Herbicides/pharmacology ; *Oryza/genetics ; Gene Flow ; Plant Weeds/genetics ; Herbicide Resistance/genetics ; Mutation ; }, abstract = {For more than two decades, weedy rice (Oryza sativa L.) has been controlled in rice fields by using imidazolinone (IMI) herbicide-resistant rice technology (Clearfield®). Outcrossing in weedy rice populations and spontaneous mutations are potential problems with herbicide-resistant crop management technologies, such as the IMI-resistant rice. The aim of this study was to characterize the mechanism of IMI herbicide resistance in weedy rice through dose-response bioassay study and evaluating amino acid substitutions in acetolactate synthase (ALS) protein. A total of 118 suspected IMI-resistant weedy rice samples, which survived in the field after an IMI herbicide application, were collected at harvest time from Türkiye in 2020 and 2021. Single-dose imazamox application experiment revealed that 38 plants survived herbicide treatment. The imazamox resistance of the surviving plants was confirmed by dose-response experiment. ALS gene region underwent a sanger DNA partial sequencing. No substitution was found in 10 samples, however, amino acid substitutions were found in 26 samples with S563N, one sample with S653T, and one sample with E630D. The S653N point is the same substitution point that serves as the origin of resistance for the Clearfield® rice varieties that are commonly cultivated in the region. It has been hypothesized that the gene flow from IMI-resistant rice may be the cause of resistance in the IMI resistant weedy rice samples with S653N. The other substitution, S653T, were considered spontaneous mutation to IMI resistance. Interestingly, the S653T mutation was detected for the first time in weedy rice. The mechanism of resistance of 10 resistant weedy rice was not confirmed in this study, however, it may be a non-target resistance or another mutation point in target site, but evidently, they did not acquire resistance by gene flow from IMI-resistant rice. It has been concluded that the effectiveness of IMI-resistant rice technology in controlling weedy rice has drastically decreased due to possible gene flow, spontaneous mutation and non-target resistance. In addition to cultural controls like clean seed, clean machinery and crop rotation, other herbicide-tolerant rice systems such as Provisia® and Roxy-RPS® rice are needed to create a diverse weedy rice management ensemble available for rice production and move towards sustainable rice farming.}, } @article {pmid38225088, year = {2024}, author = {Ohta, K and Sada, Y}, title = {Inheritance and stacking effect of mutant ALS genes in Schoenoplectiella juncoides (Roxb.) Lye (Cyperaceae).}, journal = {Pesticide biochemistry and physiology}, volume = {198}, number = {}, pages = {105745}, doi = {10.1016/j.pestbp.2023.105745}, pmid = {38225088}, issn = {1095-9939}, mesh = {*Lye/pharmacology ; *Cyperaceae/genetics ; *Herbicides/pharmacology ; Mutation ; Alleles ; Herbicide Resistance/genetics ; *Acetolactate Synthase/genetics ; }, abstract = {Schoenoplectiella juncoides, a noxious sedge weed in Japanese rice paddy, has two ALS genes, and ALS-inhibitor-resistant plants have a mutation in one of the ALS genes. The authors aimed (a) to quantitate the effect of the number of mutant alleles of ALS genes on whole-plant resistance of S. juncoides and (b) to clarify a mode of inheritance of the resistance by investigating resistance levels of the progenies of a hybrid between two S. juncoides plants with Trp574Leu substitution in different ALS. A dose-response analysis on the parental lines and the F1 population suggested that the two ALS genes contribute equally to whole-plant resistant levels. A dose-response study on the F2 population indicated that it could be classified into five groups based on the sensitivities to metsulfuron-methyl. The five groups (in ascending order of resistance levels) were considered to have zero, one, two, three, and four mutant alleles. The stacking effect of mutant alleles on resistance enhancement was more significant when the number of mutant alleles was low than when it was high; in other words, each additional mutant allele stacking increases plant resistance, but the effect saturates as the number of mutant alleles increases. A chi-square test supported that the segregation ratio of the five groups corresponds to 1:4:6:4:1 of Mendelian independence for the two ALS loci.}, } @article {pmid38225062, year = {2024}, author = {Xu, X and Zhao, B and Li, B and Shen, B and Qi, Z and Wang, J and Cui, H and Chen, S and Wang, G and Liu, X}, title = {Trp-574-Leu mutation and metabolic resistance by cytochrome P450 gene conferred high resistance to ALS-inhibiting herbicides in Descurainia sophia.}, journal = {Pesticide biochemistry and physiology}, volume = {198}, number = {}, pages = {105708}, doi = {10.1016/j.pestbp.2023.105708}, pmid = {38225062}, issn = {1095-9939}, mesh = {*Acetolactate Synthase/antagonists & inhibitors/metabolism ; *Arylsulfonates ; *Brassicaceae/drug effects/genetics ; Cytochrome P-450 Enzyme System/genetics ; Herbicide Resistance/genetics ; *Herbicides/pharmacology ; Mutation ; }, abstract = {Descurainia sophia (flixweed) is a troublesome weed in winter wheat fields in North China. Resistant D. sophia populations with different acetolactate synthetase (ALS) mutations have been reported in recent years. In addition, metabolic resistance to ALS-inhibiting herbicides has also been identified. In this study, we collected and purified two resistant D. sophia populations (R1 and R2), which were collected from winter wheat fields where tribenuron-methyl provided no control of D. sophia at 30 g a.i. ha[-1]. Whole plant bioassay and ALS activity assay results showed the R1 and R2 populations had evolved high-level resistance to tribenuron-methyl and florasulam and cross-resistance to imazethapyr and pyrithiobac‑sodium. The two ALS genes were cloned from the leaves of R1 and R2 populations, ALS1 (2004 bp) and ALS2 (1998 bp). A mutation of Trp 574 to Leu in ALS1 was present in both R1 and R2. ALS1 and ALS2 were cloned from R1 and R2 populations respectively and transferred into Arabidopsis thaliana. Homozygous T3 transgenic seedlings with ALS1 of R1 or R2 were resistant to ALS-inhibiting herbicides and the resistant levels were the same. Transgenic seedlings with ALS2 from R1 or R2 were susceptible to ALS-inhibiting herbicides. Treatment with cytochrome P450 inhibitor malathion decreased the resistant levels to tribenuron-methyl in R1 and R2. RNA-Seq was used to identify target cytochrome P450 genes possibly involved in resistance to ALS-inhibiting herbicides. There were five up-regulated differentially expressed cytochrome P450 genes: CYP72A15, CYP83B1, CYP81D8, CYP72A13 and CYP71A12. Among of them, CYP72A15 had the highest expression level in R1 and R2 populations. The R1 and R2 populations of D. sophia have evolved resistance to ALS-inhibiting herbicides due to Trp 574 Leu mutation in ALS1 and possibly other mechanisms. The resistant function of CYP72A15 needs further research.}, } @article {pmid38224498, year = {2024}, author = {Urban, MW and Charsar, BA and Heinsinger, NM and Markandaiah, SS and Sprimont, L and Zhou, W and Brown, EV and Henderson, NT and Thomas, SJ and Ghosh, B and Cain, RE and Trotti, D and Pasinelli, P and Wright, MC and Dalva, MB and Lepore, AC}, title = {EphrinB2 knockdown in cervical spinal cord preserves diaphragm innervation in a mutant SOD1 mouse model of ALS.}, journal = {eLife}, volume = {12}, number = {}, pages = {}, pmid = {38224498}, issn = {2050-084X}, support = {R01 NS079702/NS/NINDS NIH HHS/United States ; R01 NS110385/NS/NINDS NIH HHS/United States ; R01NS109150/NS/NINDS NIH HHS/United States ; R21 NS090912/NS/NINDS NIH HHS/United States ; T32 GM144302/GM/NIGMS NIH HHS/United States ; R01 NS109150/NS/NINDS NIH HHS/United States ; R01NS110385/NS/NINDS NIH HHS/United States ; R01NS079702/NS/NINDS NIH HHS/United States ; RF1AG057882/NS/NINDS NIH HHS/United States ; R21NS090912/NS/NINDS NIH HHS/United States ; RF1 AG057882/AG/NIA NIH HHS/United States ; }, mesh = {Animals ; Humans ; Mice ; *Amyotrophic Lateral Sclerosis/pathology ; Astrocytes/metabolism ; *Cervical Cord/metabolism/pathology ; Diaphragm/innervation ; Disease Models, Animal ; *Ephrin-B2/genetics ; Mice, Transgenic ; *Neurodegenerative Diseases/pathology ; Superoxide Dismutase-1/genetics/metabolism ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by motor neuron loss. Importantly, non-neuronal cell types such as astrocytes also play significant roles in disease pathogenesis. However, mechanisms of astrocyte contribution to ALS remain incompletely understood. Astrocyte involvement suggests that transcellular signaling may play a role in disease. We examined contribution of transmembrane signaling molecule ephrinB2 to ALS pathogenesis, in particular its role in driving motor neuron damage by spinal cord astrocytes. In symptomatic SOD1[G93A] mice (a well-established ALS model), ephrinB2 expression was dramatically increased in ventral horn astrocytes. Reducing ephrinB2 in the cervical spinal cord ventral horn via viral-mediated shRNA delivery reduced motor neuron loss and preserved respiratory function by maintaining phrenic motor neuron innervation of diaphragm. EphrinB2 expression was also elevated in human ALS spinal cord. These findings implicate ephrinB2 upregulation as both a transcellular signaling mechanism in mutant SOD1-associated ALS and a promising therapeutic target.}, } @article {pmid38223824, year = {2024}, author = {Lee, MY and Kim, M}, title = {Effects of Red ginseng on neuroinflammation in neurodegenerative diseases.}, journal = {Journal of ginseng research}, volume = {48}, number = {1}, pages = {20-30}, pmid = {38223824}, issn = {1226-8453}, abstract = {Red ginseng (RG) is widely used as a herbal medicine. As the human lifespan has increased, numerous diseases have developed, and RG has also been used to treat various diseases. Neurodegenerative diseases are major problems that modern people face through their lives. Neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis are featured by progressive nerve system damage. Recently, neuroinflammation has emerged as a degenerative factor and is an immune response in which cytokines with nerve cells that constitute the nervous system. RG, a natural herbal medicine with fewer side effects than chemically synthesized drugs, is currently in the spotlight. Therefore, we reviewed studies reporting the roles of RG in treating neuroinflammation and neurodegenerative diseases and found that RG might help alleviate neurodegenerative diseases by regulating neuroinflammation.}, } @article {pmid38222431, year = {2023}, author = {Turabieh, H and Afshar, AS and Statland, J and Song, X and , }, title = {Towards a Machine Learning Empowered Prognostic Model for Predicting Disease Progression for Amyotrophic Lateral Sclerosis.}, journal = {AMIA ... Annual Symposium proceedings. AMIA Symposium}, volume = {2023}, number = {}, pages = {718-725}, pmid = {38222431}, issn = {1942-597X}, mesh = {Humans ; Prognosis ; *Amyotrophic Lateral Sclerosis/diagnosis ; Disease Progression ; Algorithms ; Machine Learning ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a rare and devastating neurodegenerative disorder that is highly heterogeneous and invariably fatal. Due to the unpredictable nature of its progression, accurate tools and algorithms are needed to predict disease progression and improve patient care. To address this need, we developed and compared an extensive set of screener-learner machine learning models to accurately predict the ALS Function-Rating-Scale (ALSFRS) score reduction between 3 and 12 months, by paring 5 state-of-arts feature selection algorithms with 17 predictive models and 4 ensemble models using the publicly available Pooled Open Access Clinical Trials Database (PRO-ACT). Our experiment showed promising results with the blender-type ensemble model achieving the best prediction accuracy and highest prognostic potential.}, } @article {pmid38220602, year = {2023}, author = {Seow-Choen, F and Ng, PKL}, title = {On the correct lectotype for Marmessoidea unicolor Redtenbacher, 1908 (Insecta: Phasmatodea).}, journal = {Zootaxa}, volume = {5360}, number = {3}, pages = {448-450}, doi = {10.11646/zootaxa.5360.3.8}, pmid = {38220602}, issn = {1175-5334}, mesh = {Animals ; *Insecta ; *Neoptera ; }, abstract = {Hennemann, F.H., Conle, O.V. & Brock, P.D. (2023) The types of Phasmatodea (= Phasmida) deposited in the Eidgenssisches Technisches Hochschulzentrum, Zrich, Switzerland (ETHZ). Zootaxa, 5278 (1), 176188. https://doi.org/10.11646/zootaxa.5278.1.10 Hovinga, H. (2010) The Sumatra Railroad: Final destination Pakan Baroe, 19431945. Brill, Leiden, 391 pp. https://doi.org/10.1163/9789004253711 ICZN [International Commission on Zoological Nomenclature] (1999) International Code of Zoological Nomenclature. International Commission of Zoological Nomenclature. 4th Edition. Adopted by the XXI General Assembly of the International Union of Biological Sciences. International Trust for Zoological Nomenclature, in association with the British Museum (Natural History), London, 338 pp. Redtenbacher, J. (1908) Die Insektenfamilie der Phasmiden. III. Phasmidae Anareolatae (Phibalosomini, Acrophyllini, Necrosciini). Wilhelm Engelmann, Leipzig, pp. 341589, pls. 1627. Seow-Choen, F. (2021) A Taxonomic Guide to Stick Insects of Peninsular Malaysia. Vol. 1. Natural History Publications, Borneo, Kota Kinabalu, 944 pp. Weidmann, W. (1936) Der Schweizer als Pionier und Kolonist in Sumatra. In: Der Schweizer Verein Deli-Sumatra (Ed.), Der Schweizer Verein Deli-Sumatra: Zum fnfzigjhrigen Bestehen, 18861936. Buchdruckerei der Neuen Zrcher Zeitung, Zrich, pp. 3348.}, } @article {pmid38220456, year = {2024}, author = {Li, Y and Guo, Y and Xia, CX and Meng, XY and Wang, X and Xu, T and Zhong, Y and Wang, F}, title = {[Echocardiographic two-dimensional strain evaluation of right ventricular function in healthy adults].}, journal = {Zhonghua xin xue guan bing za zhi}, volume = {52}, number = {1}, pages = {58-63}, doi = {10.3760/cma.j.cn112148-20231019-00348}, pmid = {38220456}, issn = {0253-3758}, support = {2020YFC2002700//National Key R & D Program/ ; BJ-2019-133//Scientific Research Project of Beijing Hospital/ ; }, mesh = {Adult ; Female ; Humans ; Male ; Cross-Sectional Studies ; *Echocardiography/methods ; Heart Ventricles/diagnostic imaging ; *Ventricular Dysfunction, Right/diagnosis ; Ventricular Function, Right ; Feasibility Studies ; }, abstract = {Objective: To explore the feasibility of using two-dimensional speckle tracking echocardiography for measuring right ventricular strain and function in healthy adults, and to analyze the impact of age and gender. Methods: This study is a cross-sectional study. Healthy adults who underwent physical examination in the Physical Examination Center of Beijing Hospital from January 1, 2020 to January 1, 2021 were included. Two researchers independently measured various right ventricular longitudinal strain indices using the Echopac software, including (global longitudinal strain (GLS), apical longitudinal strain (ALS), midventricle longitudinal strain (MLS), basal longitudinal strain (BLS), free wall GLS (FWGLS), free wall ALS (FWALS), free wall MLS (FWMLS) and free wall BLS (FWBLS)) as well as tricuspid annular plane systolic excursion (TAPSE) and right ventricle-fraction of area change (RVFAC). The above indicators were taken as the average of two physicians. The consistency of the measurements by two physicians was evaluated by the within-group correlation coefficient (ICC). Results: A total of 233 subjects were included, including 137 males, aged (58.5±14.2) years. ICC values was all above 0.8 with excellent agreement. The values of FWGLS and GLS in healthy adults were -26.63% and -21.89%, respectively. There was no statistically significant difference in TAPSE ((2.06±0.41)cm vs. (2.10±0.39)cm, P=0.510) and RVFAC ((51.17±9.91)% vs. (50.89±8.65)%, P=0.826) between males and females. The values of various right ventricular long axis strain indicators (GLS, ALS, MLS, BLS, FWGLS, FWMLS, FWMLS, FWBLS) in females aged 18 to 40 and 41 to 65 years were higher than those in males of the same age (all P<0.05), while there was no statistically significant difference in the values of various right ventricular long axis strain indicators between the sexes in subjects aged 65 years and above (all P>0.05). In females, the right ventricular GLS, ALS, MLS, FWGLS, FWALS, FWMLS, and FWBLS values in the groups aged 18 to 40 and 41 to 65 years were significantly higher than those in the group aged 65 years and above (all P<0.05). In contrast, no significant differences were found in these indices among different age groups in males (all P>0.05). Conclusions: Using two-dimensional speckle tracking technology in echocardiography to measure right ventricular strain indicators is feasible and highly reproducible. Gender and age have an impact on right ventricular strain indicators.}, } @article {pmid38220307, year = {2024}, author = {Carabajal, MD and Bortolato, SA and Lisandrini, FT and Olivieri, AC}, title = {An exhaustive analysis of the use of image moments for second-order calibration. A comparison with multivariate curve resolution-alternating least-squares.}, journal = {Analytica chimica acta}, volume = {1288}, number = {}, pages = {342177}, doi = {10.1016/j.aca.2023.342177}, pmid = {38220307}, issn = {1873-4324}, abstract = {BACKGROUND: the chemometric processing of second-order chromatographic-spectral data is usually carried out with the aid of multivariate curve resolution-alternating least-squares (MCR-ALS). Recently, an alternative procedure was described based on the estimation of image moments for each data matrix and subsequent application of multiple linear regression after suitable variable selection.

RESULTS: The analysis of both simulated and experimental data leads to the conclusion that the image moment method, although can cope with chromatographic lack of reproducibility across injections, it only performs well in the absence of uncalibrated interferents. MCR-ALS, on the other hand, provides good analytical results in all studied situations, whether the test samples contain uncalibrated interferents or not.

SIGNIFICANCE: The results are useful to assess the real usefulness of newly proposed methodologies for second-order calibration in the case of chromatographic-spectral data sets, especially when samples contain unexpected chemical constituents.}, } @article {pmid38220221, year = {2024}, author = {Castro, J and Oliveira Santos, M and Swash, M and de Carvalho, M}, title = {Segmental motor neuron dysfunction in amyotrophic lateral sclerosis: Insights from H reflex paradigms.}, journal = {Muscle & nerve}, volume = {69}, number = {3}, pages = {303-312}, doi = {10.1002/mus.28035}, pmid = {38220221}, issn = {1097-4598}, support = {//Biogen/ ; }, mesh = {Humans ; Middle Aged ; *Amyotrophic Lateral Sclerosis ; H-Reflex/physiology ; Motor Neurons/physiology ; Muscle, Skeletal ; Spine ; }, abstract = {INTRODUCTION/AIMS: In amyotrophic lateral sclerosis (ALS), the role of spinal interneurons in ALS is underrecognized. We aimed to investigate pre- and post-synaptic modulation of spinal motor neuron excitability by studying the H reflex, to understand spinal interneuron function in ALS.

METHODS: We evaluated the soleus H reflex, and three different modulation paradigms, to study segmental spinal inhibitory mechanisms. Homonymous recurrent inhibition (H'RI) was assessed using the paired H reflex technique. Presynaptic inhibition of Ia afferents (H'Pre) was evaluated using D1 inhibition after stimulation of the common peroneal nerve. We also studied inhibition of the H reflex after cutaneous stimulation of the sural nerve (H'Pos).

RESULTS: Fifteen ALS patients (median age 57.0 years), with minimal signs of lower motor neuron involvement and good functional status, and a control group of 10 healthy people (median age 57.0 years) were studied. ALS patients showed reduced inhibition, compared to controls, in all paradigms (H'RI 0.35 vs. 0.11, p = .036; H'Pre 1.0 vs. 5.0, p = .001; H'Pos 0.0 vs. 2.5, p = .031). The clinical UMN score was a significant predictor of the amount of recurrent and presynaptic inhibition.

DISCUSSION: Spinal inhibitory mechanisms are impaired in ALS. We argue that hyperreflexia could be associated with dysfunction of spinal inhibitory interneurons. In this case, an interneuronopathy could be deemed a major feature of ALS.}, } @article {pmid38218903, year = {2024}, author = {Lee, MH and Kang, S and Um, KH and Lee, SW and Hwang, H and Baek, K and Choi, JW}, title = {Brain-targeted delivery of neuroprotective survival gene minimizing hematopoietic cell contamination: implications for Parkinson's disease treatment.}, journal = {Journal of translational medicine}, volume = {22}, number = {1}, pages = {53}, pmid = {38218903}, issn = {1479-5876}, support = {NRF-2017R1A5A2014768//Ministry of Science and ICT, South Korea/ ; NRF-2022R1A2C2009281//Ministry of Science and ICT, South Korea/ ; NRF-2019R1A2C1006752//Ministry of Science and ICT, South Korea/ ; 21153MFDS601//Ministry of Food and Drug Safety/ ; }, mesh = {Animals ; *Parkinson Disease/genetics/therapy ; Leukocytes, Mononuclear ; Brain/metabolism ; Genetic Therapy/methods ; Transgenes ; Genetic Vectors ; Dependovirus/genetics ; }, abstract = {BACKGROUND: Neurodegenerative diseases, including Parkinson's disease, Amyotropic Lateral Sclerosis (ALS) and Alzheimer's disease, present significant challenges for therapeutic development due to drug delivery restrictions and toxicity concerns. Prevailing strategies often employ adeno-associated viral (AAV) vectors to deliver neuroprotective survival genes directly into the central nervous system (CNS). However, these methods have been limited by triggering immunogenic responses and risk of tumorigenicity, resulting from overexpression of survival genes in peripheral blood mononuclear cells (PBMC), thereby increasing the risk of tumorigenicity in specific immune cells. Thus, by coding selectively suppressive microRNA (miRNA) target sequences in AAV genome, we designed CNS-targeted neuroprotective gene expression vector system without leakage to blood cells.

METHODS: To minimize the potential for transgene contamination in the blood, we designed a CNS-specific AAV system. Our system utilized a self-complementary AAV (scAAV), encoding a quadruple repeated target sequence of the hematopoietic cell-specific miR142-3p at the 3' untranslated region (UTR). As a representative therapeutic survival gene for Parkinson's disease treatment, we integrated DX2, an antagonistic splice variant of the apoptotic gene AIMP2, known to be implicated in Parkinson's disease, into the vector.

RESULTS: This configuration ensured that transgene expression was stringently localized to the CNS, even if the vector found its way into the blood cells. A single injection of scAAV-DX2 demonstrated marked improvement in behavior and motor activity in animal models of Parkinson's disease induced by either Rotenone or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Importantly, comprehensive preclinical data adhering to Good Laboratory Practice (GLP) standards revealed no adverse effects in the treated animals.

CONCLUSIONS: Our CNS-specific vector system, which encodes a survival transgene DX2, signifies a promising avenue for safe gene therapy, avoiding unintended expression of survival gene in blood cells, applicable to various neurodegenerative diseases.}, } @article {pmid38218579, year = {2024}, author = {Huo, D and Liang, W and Wang, D and Liu, Q and Wang, H and Wang, Y and Zhang, C and Cong, C and Su, X and Tan, X and Zhang, W and Han, L and Zhang, D and Wang, M and Feng, H}, title = {Roflupram alleviates autophagy defects and reduces mutant hSOD1-induced motor neuron damage in cell and mouse models of amyotrophic lateral sclerosis.}, journal = {Neuropharmacology}, volume = {247}, number = {}, pages = {109812}, doi = {10.1016/j.neuropharm.2023.109812}, pmid = {38218579}, issn = {1873-7064}, mesh = {Mice ; Humans ; Animals ; *Amyotrophic Lateral Sclerosis/drug therapy/genetics/metabolism ; Superoxide Dismutase-1/genetics/metabolism ; AMP-Activated Protein Kinases/metabolism ; Superoxide Dismutase/genetics/metabolism ; Motor Neurons ; Spinal Cord/metabolism ; Mice, Transgenic ; Autophagy ; Disease Models, Animal ; *Benzene Derivatives ; *Furans ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal and incurable disease involving motor neuron (MN) degeneration and is characterized by ongoing myasthenia and amyotrophia in adults. Most ALS patients die of respiratory muscle paralysis after an average of 3-5 years. Defective autophagy in MNs is considered an important trigger of ALS pathogenesis. Roflupram (ROF) was demonstrated to activate autophagy in microglial cells and exert protective effects against Parkinson's disease (PD) and Alzheimer's disease (AD). Therefore, our research aimed to investigate the efficacy and mechanism of ROF in treating ALS both in vivo and in vitro. We found that ROF could delay disease onset and prolong the survival of hSOD1-G93A transgenic mice. Moreover, ROF protected MNs in the anterior horn of the spinal cord, activated the AMPK/ULK1 signaling pathway, increased autophagic flow, and reduced SOD1 aggregation. In an NSC34 cell line stably transfected with hSOD1-G93A, ROF protected against cellular damage caused by hSOD1-G93A. Moreover, we have demonstrated that ROF inhibited gliosis in ALS model mice. Collectively, our study suggested that ROF is neuroprotective in ALS models and the AMPK/ULK1 signaling pathway is a potential therapeutic target in ALS, which increases autophagic flow and reduces SOD1 aggregation.}, } @article {pmid38218077, year = {2024}, author = {Di Lazzaro, V and Ranieri, F and Bączyk, M and de Carvalho, M and Dileone, M and Dubbioso, R and Fernandes, S and Kozak, G and Motolese, F and Ziemann, U}, title = {Novel approaches to motoneuron disease/ALS treatment using non-invasive brain and spinal stimulation: IFCN handbook chapter.}, journal = {Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology}, volume = {158}, number = {}, pages = {114-136}, doi = {10.1016/j.clinph.2023.12.012}, pmid = {38218077}, issn = {1872-8952}, mesh = {Animals ; Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/therapy ; *Transcranial Direct Current Stimulation ; *Motor Neuron Disease/diagnosis/therapy ; Motor Neurons/physiology ; Brain ; Transcranial Magnetic Stimulation/methods ; }, abstract = {Non-invasive brain stimulation techniques have been exploited in motor neuron disease (MND) with multifold objectives: to support the diagnosis, to get insights in the pathophysiology of these disorders and, more recently, to slow down disease progression. In this review, we consider how neuromodulation can now be employed to treat MND, with specific attention to amyotrophic lateral sclerosis (ALS), the most common form with upper motoneuron (UMN) involvement, taking into account electrophysiological abnormalities revealed by human and animal studies that can be targeted by neuromodulation techniques. This review article encompasses repetitive transcranial magnetic stimulation methods (including low-frequency, high-frequency, and pattern stimulation paradigms), transcranial direct current stimulation as well as experimental findings with the newer approach of trans-spinal direct current stimulation. We also survey and discuss the trials that have been performed, and future perspectives.}, } @article {pmid38217607, year = {2024}, author = {Mázala, DAG and Chen, D and Chin, ER}, title = {SERCA1 Overexpression in Skeletal Muscle Attenuates Muscle Atrophy and Improves Motor Function in a Mouse Model of ALS.}, journal = {Journal of neuromuscular diseases}, volume = {11}, number = {2}, pages = {315-326}, pmid = {38217607}, issn = {2214-3602}, support = {T32 AG000268/AG/NIA NIH HHS/United States ; }, mesh = {Mice ; Animals ; *Amyotrophic Lateral Sclerosis ; Endoplasmic Reticulum Chaperone BiP ; Calcium/metabolism ; Fura-2/metabolism ; Muscle, Skeletal ; Mice, Transgenic ; Muscular Atrophy/metabolism ; Calcium-Transporting ATPases/metabolism ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is characterized by progressive loss of muscle mass and muscle function. Previous work from our lab demonstrated that skeletal muscles from a mouse model of ALS show elevated intracellular calcium (Ca2+) levels and heightened endoplasmic reticulum (ER) stress.

OBJECTIVE: To investigate whether overexpression of sarcoplasmic reticulum (SR) Ca2+ ATPase 1 (SERCA1) in skeletal muscle would improve intracellular Ca2+ handling, attenuate ER stress, and improve motor function ALS transgenic mice.

METHODS: B6SJL-Tg (SOD1*G93A)1Gur/J (ALS-Tg) mice were bred with skeletal muscle α-actinin SERCA1 overexpressing mice to generate wild type (WT), SERCA1 overexpression (WT/+SERCA1), ALS-Tg, and SERCA1 overexpressing ALS-Tg (ALS-Tg/+SERCA1) mice. Motor function (grip test) was assessed weekly and skeletal muscles were harvested at 16 weeks of age to evaluate muscle mass, SR-Ca2+ ATPase activity, levels of SERCA1 and ER stress proteins - protein disulfide isomerase (PDI), Grp78/BiP, and C/EBP homologous protein (CHOP). Single muscle fibers were also isolated from the flexor digitorum brevis muscle to assess changes in resting and peak Fura-2 ratios.

RESULTS: ALS-Tg/+SERCA1 mice showed improved motor function, delayed onset of disease, and improved muscle mass compared to ALS-Tg. Further, ALS-Tg/+SERCA1 mice returned levels of SERCA1 protein and SR-Ca2+ ATPase activity back to levels in WT mice. Unexpectedly, SERCA-1 overexpression increased levels of the ER stress maker Grp78/BiP in both WT and ALS-Tg mice, while not altering protein levels of PDI or CHOP. Lastly, single muscle fibers from ALS-Tg/+SERCA1 had similar resting but lower peak Fura-2 levels (at 30 Hz and 100 Hz) compared to ALS-Tg mice.

CONCLUSIONS: These data indicate that SERCA1 overexpression attenuates the progressive loss of muscle mass and maintains motor function in ALS-Tg mice while not lowering resting Ca2+ levels or ER stress.}, } @article {pmid38217066, year = {2024}, author = {Tsagakis, I and Yamanaka, K}, title = {An open chat with… Koji Yamanaka.}, journal = {FEBS open bio}, volume = {14}, number = {2}, pages = {162-164}, pmid = {38217066}, issn = {2211-5463}, mesh = {Humans ; Male ; *Amyotrophic Lateral Sclerosis/genetics ; }, abstract = {Koji Yamanaka is a Professor at the Research Institute of Environmental Medicine at Nagoya University of Japan. His research interests lie in understanding the mechanism of onset and progression of motor neuron disease as well as the role of glial cells in Alzheimer's disease neuroinflammation. Koji has been serving on the FEBS Open Bio Editorial Board since 2013. In this interview, he explains the implications of recent findings in neurobiology for amyotrophic lateral sclerosis, provides updates on the research environment in Japan and discusses how editors might use their position to positively influence academic culture.}, } @article {pmid38216448, year = {2024}, author = {Van Daele, SH and Masrori, P and Van Damme, P and Van Den Bosch, L}, title = {The sense of antisense therapies in ALS.}, journal = {Trends in molecular medicine}, volume = {30}, number = {3}, pages = {252-262}, doi = {10.1016/j.molmed.2023.12.003}, pmid = {38216448}, issn = {1471-499X}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy/drug therapy ; Oligonucleotides, Antisense/therapeutic use ; RNA Splicing ; }, abstract = {Treatment of patients with amyotrophic lateral sclerosis (ALS) has entered a new era now that encouraging results about antisense oligonucleotides (ASOs) are becoming available and a first ASO therapy for ALS has been approved by the FDA. Moreover, there is hope not only that ALS can be stopped but also that symptoms can be reversed. Until now, degrading ASOs seemed to be successful mostly for rarer forms of familial ALS. However, the first attempts to correct mis-splicing events in sporadic ALS are underway, as well as a clinical trial examining interference with a genetic modifier. In this review, we discuss the current status of using ASOs in ALS and the possibilities and pitfalls of this therapeutic strategy.}, } @article {pmid38214845, year = {2024}, author = {Fang, A and Zhao, Y and Yang, P and Zhang, X and Giovannucci, EL}, title = {Vitamin D and human health: evidence from Mendelian randomization studies.}, journal = {European journal of epidemiology}, volume = {39}, number = {5}, pages = {467-490}, pmid = {38214845}, issn = {1573-7284}, support = {81803219//National Natural Science Foundation of China/ ; 2018A030310335//Natural Science Foundation of Guangdong Province/ ; }, mesh = {Humans ; *Mendelian Randomization Analysis ; *Vitamin D/blood/analogs & derivatives ; Vitamin D Deficiency/epidemiology/complications/genetics ; }, abstract = {We summarized the current evidence on vitamin D and major health outcomes from Mendelian randomization (MR) studies. PubMed and Embase were searched for original MR studies on vitamin D in relation to any health outcome from inception to September 1, 2022. Nonlinear MR findings were excluded due to concerns about the validity of the statistical methods used. A meta-analysis was preformed to synthesize study-specific estimates after excluding overlapping samples, where applicable. The methodological quality of the included studies was evaluated according to the STROBE-MR checklist. A total of 133 MR publications were eligible for inclusion in the analyses. The causal association between vitamin D status and 275 individual outcomes was examined. Linear MR analyses showed genetically high 25-hydroxyvitamin D (25(OH)D) concentrations were associated with reduced risk of multiple sclerosis incidence and relapse, non-infectious uveitis and scleritis, psoriasis, femur fracture, leg fracture, amyotrophic lateral sclerosis, anorexia nervosa, delirium, heart failure, ovarian cancer, non-alcoholic fatty liver disease, dyslipidemia, and bacterial pneumonia, but increased risk of Behçet's disease, Graves' disease, kidney stone disease, fracture of radium/ulna, basal cell carcinoma, and overall cataracts. Stratified analyses showed that the inverse association between genetically predisposed 25(OH)D concentrations and multiple sclerosis risk was significant and consistent regardless of the genetic instruments GIs selected. However, the associations with most of the other outcomes were only pronounced when using genetic variants not limited to those in the vitamin D pathway as GIs. The methodological quality of the included MR studies was substantially heterogeneous. Current evidence from linear MR studies strongly supports a causal role of vitamin D in the development of multiple sclerosis. Suggestive support for a number of other health conditions could help prioritize conditions where vitamin D may be beneficial or harmful.}, } @article {pmid38213752, year = {2024}, author = {}, title = {Erratum: Estimated Familial Amyotrophic Lateral Sclerosis Proportion: A Literature Review and Meta-Analysis.}, journal = {Neurology. Genetics}, volume = {10}, number = {1}, pages = {e200131}, pmid = {38213752}, issn = {2376-7839}, abstract = {[This corrects the article DOI: 10.1212/NXG.0000000000200109.].}, } @article {pmid38213309, year = {2024}, author = {Eisen, A and Vucic, S and Mitsumoto, H}, title = {History of ALS and the competing theories on pathogenesis: IFCN handbook chapter.}, journal = {Clinical neurophysiology practice}, volume = {9}, number = {}, pages = {1-12}, pmid = {38213309}, issn = {2467-981X}, abstract = {Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative disorder of the human motor system, first described in the 19th Century. The etiology of ALS appears to be multifactorial, with a complex interaction of genetic, epigenetic, and environmental factors underlying the onset of disease. Importantly, there are no known naturally occurring animal models, and transgenic mouse models fail to faithfully reproduce ALS as it manifests in patients. Debate as to the site of onset of ALS remain, with three competing theories proposed, including (i) the dying-forward hypothesis, whereby motor neuron degeneration is mediated by hyperexcitable corticomotoneurons via an anterograde transsynaptic excitotoxic mechanism, (ii) dying-back hypothesis, proposing the ALS begins in the peripheral nervous system with a toxic factor(s) retrogradely transported into the central nervous system and mediating upper motor neuron dysfunction, and (iii) independent hypothesis, suggesting that upper and lower motor neuron degenerated independently. Transcranial magnetic stimulation studies, along with pathological and genetic findings have supported the dying forward hypothesis theory, although the science is yet to be settled. The review provides a historical overview of ALS, discusses phenotypes and likely pathogenic mechanisms.}, } @article {pmid38213020, year = {2024}, author = {Chen, M and Guo, X and Guo, J and Shi, C and Wu, Y and Chen, L and Mao, R and Fan, Y}, title = {Cytoplasmic Accumulation of Histones Induced by BET Inhibition Protects Cells from C9orf72 Poly(PR)-Induced Cell Death.}, journal = {Advanced biology}, volume = {8}, number = {3}, pages = {e2300334}, doi = {10.1002/adbi.202300334}, pmid = {38213020}, issn = {2701-0198}, support = {31970616//National Natural Science Foundation of China/ ; 81873531//National Natural Science Foundation of China/ ; BK20211330//Jiangsu Provincial Natural Science Foundation/ ; KYCX20_2796//Graduate Research and Innovation Projects of Jiangsu Province/ ; KYCX22_3362//Graduate Research and Innovation Projects of Jiangsu Province/ ; }, mesh = {*Histones/genetics/metabolism/pharmacology ; C9orf72 Protein/genetics/metabolism/pharmacology ; *Nuclear Proteins/genetics/metabolism/pharmacology ; DNA Repeat Expansion ; Transcription Factors/genetics/metabolism/pharmacology ; Dipeptides/genetics/metabolism/pharmacology ; Cell Death/genetics ; }, abstract = {Repeat dipeptides such as poly(proline-arginine) (polyPR) are generated from the hexanucleotide GGGGCC repeat expansions in the C9orf72 gene. These dipeptides are often considered as the genetic cause of familial amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). In the study, fluorescein isothiocyanate (FITC) labeled PR20 is used to investigate PR20-induced cell death. The findings reveal that the cell death induced by PR20 is dependent on its nuclear distribution and can be blocked by a nuclear import inhibitor called importazole. Further investigation reveals that BRD4 inhibitors, such as JQ-1 and I-BET762, restrict cytoplasmic localization of PR20, thereby reducing its cytotoxic effect. Mechanistically, the inhibition of BRD4 leads to an increase in the expression of numerous histones, resulting in the accumulation of histones in the cytoplasm. These cytoplasmic histones associate with PR20 and limit its distribution within the nucleus. Notably, the ectopic expression of histones alone is enough to confer protection to cells treated with PR20. In addition, phenylephrine (PE) induces cellular hypertrophy and cytoplasmic distribution of histone, which also helps protect cells from PR20-induced cell death. The research suggests that temporarily inducing the presence of cytoplasmic histones may alleviate the neurotoxic effects of dipeptide repeat proteins.}, } @article {pmid38212835, year = {2024}, author = {Zaccai, S and Nemirovsky, A and Lerner, L and Alfahel, L and Eremenko, E and Israelson, A and Monsonego, A}, title = {CD4 T-cell aging exacerbates neuroinflammation in a late-onset mouse model of amyotrophic lateral sclerosis.}, journal = {Journal of neuroinflammation}, volume = {21}, number = {1}, pages = {17}, pmid = {38212835}, issn = {1742-2094}, support = {3-16148//Ministry of Science, Technology and Space/ ; 284/19//Israel Science Foundation grant/ ; }, mesh = {Humans ; Mice ; Animals ; *Amyotrophic Lateral Sclerosis/metabolism ; Superoxide Dismutase-1/genetics/metabolism ; CD4-Positive T-Lymphocytes/metabolism ; Mice, Transgenic ; Neuroinflammatory Diseases ; T-Cell Senescence ; Superoxide Dismutase/genetics/metabolism ; Spinal Cord/metabolism ; Disease Progression ; Disease Models, Animal ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is an adult-onset progressive neurodegenerative disorder characterized by the loss of upper and lower motor neurons in the brain and spinal cord. Accumulating evidence suggests that ALS is not solely a neuronal cell- or brain tissue-autonomous disease and that neuroinflammation plays a key role in disease progression. Furthermore, whereas both CD4 and CD8 T cells were observed in spinal cords of ALS patients and in mouse models of the disease, their role in the neuroinflammatory process, especially considering their functional changes with age, is not fully explored. In this study, we revealed the structure of the CD4 T-cell compartment during disease progression of early-onset SOD1[G93A] and late-onset SOD1[G37R] mouse models of ALS. We show age-related changes in the CD4 T-cell subset organization between these mutant SOD1 mouse models towards increased frequency of effector T cells in spleens of SOD1[G37R] mice and robust infiltration of CD4 T cells expressing activation markers and the checkpoint molecule PD1 into the spinal cord. The frequency of infiltrating CD4 T cells correlated with the frequency of infiltrating CD8 T cells which displayed a more exhausted phenotype. Moreover, RNA-Seq and immunohistochemistry analyses of spinal cords from SOD1[G37R] mice with early clinical symptoms demonstrated immunological trajectories reminiscent of a neurotoxic inflammatory response which involved proinflammatory T cells and antigen presentation related pathways. Overall, our findings suggest that age-related changes of the CD4 T cell landscape is indicative of a chronic inflammatory response, which aggravates the disease process and can be therapeutically targeted.}, } @article {pmid38212665, year = {2024}, author = {Jang, MS and Yoo, SH and Kim, MS and Cho, B and Kim, KH and Shin, J and Hwang, I and Choi, SJ and Sung, JJ and Lee, SY}, title = {Healthcare Utilization and Supportive Care Timing in South Korean People Living With Amyotrophic Lateral Sclerosis: A Single-Center Retrospective Study.}, journal = {Journal of clinical neurology (Seoul, Korea)}, volume = {20}, number = {2}, pages = {166-174}, pmid = {38212665}, issn = {1738-6586}, support = {27302C0115/ES/NIEHS NIH HHS/United States ; }, abstract = {BACKGROUND AND PURPOSE: Despite the growing demands and challenges faced by patients with amyotrophic lateral sclerosis (ALS) in accessing healthcare services, our understanding of this access remains poor. This study aimed to investigate the healthcare utilization patterns and timing of nutritional and respiration support in patients with ALS in South Korea.

METHODS: A retrospective cohort study was conducted on patients diagnosed with ALS at a single tertiary hospital between 2016 and 2019 and followed up for 2 years. We evaluated patient characteristics, healthcare utilization (hospital admissions, outpatient visits, and emergency department [ED] visits), and the timing of nutritional and respiration support (noninvasive positive pressure ventilation [NIPPV], tracheostomy, gastrostomy, and nasogastric tube) at 6-month intervals from the first outpatient visit.

RESULTS: Among the 143 included patients, 73.4% were admitted at least once, 18.9% experienced unplanned admissions, and 30.1% visited the ED at least once during the study period. The most-common reason for ED visits was neurological symptoms during the first 6 months (59.1%), followed by respiratory symptoms. One fifth of patients who visited the ED underwent tracheostomy (20.9%) or NIPPV (20.9%). Two years after the first visit, 32.2% used a ventilator, and 13.3%, 26.6%, and 6.3% had undergone tracheostomy, gastrostomy, and nasogastric tube insertion, respectively.

CONCLUSIONS: During the 2 years following their first outpatient visit, 20% of patients with ALS experienced unplanned admissions and 30% visited the ED. An active and prompt supportive-care program should be implemented to ensure timely functional support in order to reduce these risks of unplanned admissions.}, } @article {pmid38212334, year = {2024}, author = {Sharma, K and Stockert, F and Shenoy, J and Berbon, M and Abdul-Shukkoor, MB and Habenstein, B and Loquet, A and Schmidt, M and Fändrich, M}, title = {Cryo-EM observation of the amyloid key structure of polymorphic TDP-43 amyloid fibrils.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {486}, pmid = {38212334}, issn = {2041-1723}, mesh = {Humans ; Amyloid/metabolism ; Cryoelectron Microscopy ; Amyloidogenic Proteins ; *Frontotemporal Lobar Degeneration/metabolism ; *Amyotrophic Lateral Sclerosis/genetics/metabolism ; DNA-Binding Proteins/metabolism ; }, abstract = {The transactive response DNA-binding protein-43 (TDP-43) is a multi-facet protein involved in phase separation, RNA-binding, and alternative splicing. In the context of neurodegenerative diseases, abnormal aggregation of TDP-43 has been linked to amyotrophic lateral sclerosis and frontotemporal lobar degeneration through the aggregation of its C-terminal domain. Here, we report a cryo-electron microscopy (cryo-EM)-based structural characterization of TDP-43 fibrils obtained from the full-length protein. We find that the fibrils are polymorphic and contain three different amyloid structures. The structures differ in the number and relative orientation of the protofilaments, although they share a similar fold containing an amyloid key motif. The observed fibril structures differ from previously described conformations of TDP-43 fibrils and help to better understand the structural landscape of the amyloid fibril structures derived from this protein.}, } @article {pmid38206346, year = {2024}, author = {Vosough, M and Salemi, A and Rockel, S and Schmidt, TC}, title = {Enhanced efficiency of MS/MS all-ion fragmentation for non-targeted analysis of trace contaminants in surface water using multivariate curve resolution and data fusion.}, journal = {Analytical and bioanalytical chemistry}, volume = {416}, number = {5}, pages = {1165-1177}, pmid = {38206346}, issn = {1618-2650}, support = {520243139//Deutsche Forschungsgemeinschaft/ ; }, abstract = {Data-independent acquisition-all-ion fragmentation (DIA-AIF) mode of mass spectrometry can facilitate wide-scope non-target analysis of contaminants in surface water due to comprehensive spectral identification. However, because of the complexity of the resulting MS[2] AIF spectra, identifying unknown pollutants remains a significant challenge, with a significant bottleneck in translating non-targeted chemical signatures into environmental impacts. The present study proposes to process fused MS[1] and MS[2] data sets obtained from LC-HRMS/MS measurements in non-targeted AIF workflows on surface water samples using multivariate curve resolution-alternating least squares (MCR-ALS). This enables straightforward assignment between precursor ions obtained from resolved MS[1] spectra and their corresponding MS[2] spectra. The method was evaluated for two sets of tap water and surface water contaminated with 14 target chemicals as a proof of concept. The data set of surface water samples consisting of 3506 MS[1] and 2170 MS[2] AIF mass spectral features was reduced to 81 components via a fused MS[1]-MS[2] MCR model that describes at least 98.8% of the data. Each component summarizes the distinct chromatographic elution of components together with their corresponding MS[1] and MS[2] spectra. MS[2] spectral similarity of more than 82% was obtained for most target chemicals. This highlights the potential of this method for unraveling the composition of MS/MS complex data in a water environment. Ultimately, the developed approach was applied to the retrospective non-target analysis of an independent set of surface water samples.}, } @article {pmid38205130, year = {2024}, author = {Izquierdo-Condoy, JS and Naranjo-Lara, P and Arias Rodríguez, FD and Puglla-Mendoza, AG and Jima-Sanmartín, J and Andrade Casanova, D and Duque-Sánchez, EP and Alegría N, N and Rojas Cadena, MG and Ortiz-Prado, E}, title = {Assessing the Proficiency in Basic and Advanced Life Support Among Physicians in Ecuador: A Cross-Sectional Study.}, journal = {Advances in medical education and practice}, volume = {15}, number = {}, pages = {25-35}, pmid = {38205130}, issn = {1179-7258}, abstract = {PURPOSE: Cardiorespiratory arrest's unpredictability poses a global health challenge, with gaps in physicians' life support knowledge potentially leading to poor patient outcomes, a factor yet unstudied among Ecuadorian physicians. This study aims to elucidate the state of physicians' theoretical knowledge in Ecuador based on Basic Life Support (BLS) and Advanced Life Support (ALS) guidelines.

PATIENTS AND METHODS: A national cross-sectional online 35-questions survey was conducted between February and March 2023 using a self-administered, expert-validated questionnaire. Participants' responses were obtained through official social media groups (WhatsApp and Facebook). The survey evaluated the theoretical knowledge of BLS and ALS, with scores based on the number of correct answers out of a maximum of 10.0 points. For descriptive analysis, frequencies, percentages, means, and standard deviations (SD) were used. The T-test and one-way ANOVA were utilized to analyze the associations between knowledge levels and demographic and academic training variables of Ecuadorian doctors. Values of p < 0.05 were considered statistically significant for all analyses.

RESULTS: The survey garnered responses from 385 physicians, with a majority being female (56.6%) and possessing less than 3 years of work experience (75.1%). Of these, 71.7% and 51.9% held BLS and ALS certifications, respectively. Knowledge scores for BLS (5.8/10 ± 1.6) surpassed those for ALS (4.7/10 ± 1.8) (p < 0.001). Physicians with less than 3 years of work experience exhibited higher knowledge scores in both BLS and ALS tests (p < 0.05).

CONCLUSION: This study revealed a notable deficiency in the theoretical knowledge of BLS and ALS among surveyed Ecuadorian physicians. Factors such as prior certification and years of work experience appeared to influence knowledge levels. Continual training and updates in life support protocols at universities and healthcare institutions are key to enhancing physicians' skills and patient outcomes.}, } @article {pmid38203614, year = {2023}, author = {Wu, Y and Chen, Y and Yu, X and Zhang, M and Li, Z}, title = {Towards Understanding Neurodegenerative Diseases: Insights from Caenorhabditis elegans.}, journal = {International journal of molecular sciences}, volume = {25}, number = {1}, pages = {}, pmid = {38203614}, issn = {1422-0067}, support = {2002472//National Health and Medical Research Council/ ; }, mesh = {Animals ; Caenorhabditis elegans/genetics ; *Neurodegenerative Diseases/genetics ; *Alzheimer Disease ; *Huntington Disease ; *Parkinson Disease ; Mammals ; }, abstract = {The elevated occurrence of debilitating neurodegenerative disorders, such as amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), Alzheimer's disease (AD), Parkinson's disease (PD) and Machado-Joseph disease (MJD), demands urgent disease-modifying therapeutics. Owing to the evolutionarily conserved molecular signalling pathways with mammalian species and facile genetic manipulation, the nematode Caenorhabditis elegans (C. elegans) emerges as a powerful and manipulative model system for mechanistic insights into neurodegenerative diseases. Herein, we review several representative C. elegans models established for five common neurodegenerative diseases, which closely simulate disease phenotypes specifically in the gain-of-function aspect. We exemplify applications of high-throughput genetic and drug screenings to illustrate the potential of C. elegans to probe novel therapeutic targets. This review highlights the utility of C. elegans as a comprehensive and versatile platform for the dissection of neurodegenerative diseases at the molecular level.}, } @article {pmid38203300, year = {2023}, author = {Wei, J and Wong, LC and Boland, S}, title = {Lipids as Emerging Biomarkers in Neurodegenerative Diseases.}, journal = {International journal of molecular sciences}, volume = {25}, number = {1}, pages = {}, pmid = {38203300}, issn = {1422-0067}, mesh = {Humans ; *Neurodegenerative Diseases/diagnosis ; *Alzheimer Disease/diagnosis ; *Parkinson Disease ; Biomarkers ; Monoglycerides ; }, abstract = {Biomarkers are molecules that can be used to observe changes in an individual's biochemical or medical status and provide information to aid diagnosis or treatment decisions. Dysregulation in lipid metabolism in the brain is a major risk factor for many neurodegenerative disorders, including frontotemporal dementia, Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. Thus, there is a growing interest in using lipids as biomarkers in neurodegenerative diseases, with the anionic phospholipid bis(monoacylglycerol)phosphate and (glyco-)sphingolipids being the most promising lipid classes thus far. In this review, we provide a general overview of lipid biology, provide examples of abnormal lysosomal lipid metabolism in neurodegenerative diseases, and discuss how these insights might offer novel and promising opportunities in biomarker development and therapeutic discovery. Finally, we discuss the challenges and opportunities of lipid biomarkers and biomarker panels in diagnosis, prognosis, and/or treatment response in the clinic.}, } @article {pmid38202942, year = {2023}, author = {Kosmyna, N and Hauptmann, E and Hmaidan, Y}, title = {A Brain-Controlled Quadruped Robot: A Proof-of-Concept Demonstration.}, journal = {Sensors (Basel, Switzerland)}, volume = {24}, number = {1}, pages = {}, pmid = {38202942}, issn = {1424-8220}, mesh = {Humans ; Animals ; Dogs ; *Robotics ; Brainwashing ; Proof of Concept Study ; *Amyotrophic Lateral Sclerosis ; Brain ; }, abstract = {Coupling brain-computer interfaces (BCIs) and robotic systems in the future can enable seamless personal assistant systems in everyday life, with the requests that can be performed in a discrete manner, using one's brain activity only. These types of systems might be of a particular interest for people with locked-in syndrome (LIS) or amyotrophic lateral sclerosis (ALS) because they can benefit from communicating with robotic assistants using brain sensing interfaces. In this proof-of-concept work, we explored how a wireless and wearable BCI device can control a quadruped robot-Boston Dynamics' Spot. The device measures the user's electroencephalography (EEG) and electrooculography (EOG) activity of the user from the electrodes embedded in the glasses' frame. The user responds to a series of questions with YES/NO answers by performing a brain-teaser activity of mental calculus. Each question-answer pair has a pre-configured set of actions for Spot. For instance, Spot was prompted to walk across a room, pick up an object, and retrieve it for the user (i.e., bring a bottle of water) when a sequence resolved to a YES response. Our system achieved at a success rate of 83.4%. To the best of our knowledge, this is the first integration of wireless, non-visual-based BCI systems with Spot in the context of personal assistant use cases. While this BCI quadruped robot system is an early prototype, future iterations may embody friendly and intuitive cues similar to regular service dogs. As such, this project aims to pave a path towards future developments in modern day personal assistant robots powered by wireless and wearable BCI systems in everyday living conditions.}, } @article {pmid38202163, year = {2023}, author = {Ueha, R and Cotaoco, C and Kondo, K and Yamasoba, T}, title = {Management and Treatment for Dysphagia in Neurodegenerative Disorders.}, journal = {Journal of clinical medicine}, volume = {13}, number = {1}, pages = {}, pmid = {38202163}, issn = {2077-0383}, abstract = {Patients with neurodegenerative disorders (NDDs) often experience functional dysphagia, which may involve dysfunction in a specific phase of swallowing or in the entire process. This review outlines the approach to dysphagia in the setting of NDDs. Distinguishing the etiology of dysphagia can be difficult, and it is important to always look out for signs pointing to NDD as the cause. Thorough diagnostic work-up is essential, and it includes a comprehensive history and physical examination, alongside swallowing function tests, such as fiberoptic endoscopic evaluation of swallowing, videofluoroscopic swallowing study, and high-resolution manometry. Management requires a multidisciplinary approach with a treatment plan tailored to each patient. This involves dietary guidance, swallowing rehabilitation, and surgery in cases in which improvement with rehabilitation is inadequate. Surgery may involve altering certain pharyngolaryngeal structures to facilitate swallowing and reduce the risk of aspiration (swallowing improvement surgery) or separating the airway and digestive tract while sacrificing laryngeal function, with the main goal of preventing aspiration (aspiration prevention surgery). Proper management stems from recognizing the impact of these disorders on swallowing and consistently finding ways to improve the quality of life of patients.}, } @article {pmid38201932, year = {2023}, author = {Sharma, H and Sharma, N and An, SSA}, title = {Unique Bioactives from Zombie Fungus (Cordyceps) as Promising Multitargeted Neuroprotective Agents.}, journal = {Nutrients}, volume = {16}, number = {1}, pages = {}, pmid = {38201932}, issn = {2072-6643}, support = {RS-2023-00251396 and 2021R1A6A1A03038996//National Research Foundation of Korea/ ; }, mesh = {*Neuroprotective Agents/pharmacology ; *Cordyceps ; *Agaricales ; Neuroprotection ; Adenosine ; }, abstract = {Cordyceps, also known as "zombie fungus", is a non-poisonous mushroom that parasitizes insects for growth and development by manipulating the host system in a way that makes the victim behave like a "zombie". These species produce promising bioactive metabolites, like adenosine, β-glucans, cordycepin, and ergosterol. Cordyceps has been used in traditional medicine due to its immense health benefits, as it boosts stamina, appetite, immunity, longevity, libido, memory, and sleep. Neuronal loss is the typical feature of neurodegenerative diseases (NDs) (Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS)) and neurotrauma. Both these conditions share common pathophysiological features, like oxidative stress, neuroinflammation, and glutamatergic excitotoxicity. Cordyceps bioactives (adenosine, N[6]-(2-hydroxyethyl)-adenosine, ergosta-7, 9 (11), 22-trien-3β-ol, active peptides, and polysaccharides) exert potential antioxidant, anti-inflammatory, and anti-apoptotic activities and display beneficial effects in the management and/or treatment of neurodegenerative disorders in vitro and in vivo. Although a considerable list of compounds is available from Cordyceps, only a few have been evaluated for their neuroprotective potential and still lack information for clinical trials. In this review, the neuroprotective mechanisms and safety profile of Cordyceps extracts/bioactives have been discussed, which might be helpful in the identification of novel potential therapeutic entities in the future.}, } @article {pmid38201303, year = {2024}, author = {Chen, L and Zhang, S and Liu, S and Gao, S}, title = {Amyotrophic Lateral Sclerosis Mechanism: Insights from the Caenorhabditis elegans Models.}, journal = {Cells}, volume = {13}, number = {1}, pages = {}, pmid = {38201303}, issn = {2073-4409}, support = {32020103007//Major International (Regional) Joint Research Project/ ; 2022YFA1206001//National Key Research and Development Program of China/ ; 32371189, 32300984//the National Natural Science Foundation of China/ ; }, mesh = {Animals ; *Amyotrophic Lateral Sclerosis/genetics ; Caenorhabditis elegans ; Motor Neurons ; Protein Aggregates ; Signal Transduction ; }, abstract = {Amyotrophic Lateral Sclerosis (ALS) is a debilitating neurodegenerative condition characterized by the progressive degeneration of motor neurons. Despite extensive research in various model animals, the cellular signal mechanisms of ALS remain elusive, impeding the development of efficacious treatments. Among these models, a well-characterized and diminutive organism, Caenorhabditis elegans (C. elegans), has emerged as a potent tool for investigating the molecular and cellular dimensions of ALS pathogenesis. This review summarizes the contributions of C. elegans models to our comprehension of ALS, emphasizing pivotal findings pertaining to genetics, protein aggregation, cellular pathways, and potential therapeutic strategies. We analyze both the merits and constraints of the C. elegans system in the realm of ALS research and point towards future investigations that could bridge the chasm between C. elegans foundational discoveries and clinical applications.}, } @article {pmid38200884, year = {2024}, author = {Fürmann, A and Syring, C and Becker, J and Sarbach, A and Weber, J and Welham Ruiters, M and Steiner, A}, title = {Prevalence of Painful Lesions of the Digits and Risk Factors Associated with Digital Dermatitis, Ulcers and White Line Disease on Swiss Cattle Farms.}, journal = {Animals : an open access journal from MDPI}, volume = {14}, number = {1}, pages = {}, pmid = {38200884}, issn = {2076-2615}, abstract = {The first aim of this study was to calculate the prevalence of painful lesions of the digits ("alarm" lesions; ALs) in Swiss dairy herds and cow-calf operations over a three-year study period. The following ALs were included in the calculation: the M2 stage of digital dermatitis (DD M2), ulcers (U), white line fissures (WLF) of moderate and high severity, white line abscesses (WLA), interdigital phlegmon (IP) and swelling of the coronet and/or bulb (SW). Between February 2020 and February 2023, digit disorders were electronically recorded during routine trimmings by 40 specially trained hoof trimmers on Swiss cattle farms participating in the national claw health programme. The data set used consisted of over 35,000 observations from almost 25,000 cows from 702 herds. While at the herd-level, the predominant AL documented in 2022 was U with 50.3% followed by WLF with 38.1%, at the cow-level, in 2022, it was DD M2 with 5.4% followed by U with 3.7%. During the study period, within-herd prevalences of ALs ranged from 0.0% to a maximum of 66.1% in 2020. The second aim of this study was to determine herd- and cow-level risk factors associated with digital dermatitis (DD), U and white line disease (WL) in dairy cows using data from 2022. While for DD, analysed herd-level factors appeared to have a greater effect on the probability of its occurrence, the presence of U and WL was mainly associated with the analysed cow-level factors. The risk for DD increased with a higher herd trimming frequency. Herds kept in tie stalls had a lower risk for DD and WL and a higher risk for U compared to herds kept in loose housing systems. Herds with predominantly Holstein Friesian cows as well as Holstein Friesian cows had a higher risk for the occurrence of DD compared to herds and cows of other breeds. With increasing parity, cows had a higher risk of developing U and WL, whereas for DD, parity was negatively associated with prevalence. Cows trimmed during the grazing period had a higher risk of U and WL than cows trimmed during the housing period. These findings may contribute to improve management measures affecting the health of the digits in farms with structures similar to those evaluated in the current study, such as small herds with frequent access to pasture. Further research is warranted to demonstrate how measures addressing the current results combined with those of individual herd risk assessments might contribute to an improvement in the health of the digits in the respective dairy herds.}, } @article {pmid38200398, year = {2024}, author = {Stenson, K and Fecteau, TE and O'Callaghan, L and Bryden, P and Mellor, J and Wright, J and Earl, L and Thomas, O and Iqbal, H and Barlow, S and Parvanta, S}, title = {Health-related quality of life across disease stages in patients with amyotrophic lateral sclerosis: results from a real-world survey.}, journal = {Journal of neurology}, volume = {271}, number = {5}, pages = {2390-2404}, pmid = {38200398}, issn = {1432-1459}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology/psychology/complications ; *Quality of Life ; Male ; Female ; Middle Aged ; Cross-Sectional Studies ; *Disease Progression ; Aged ; Adult ; Severity of Illness Index ; Surveys and Questionnaires ; Caregivers/psychology ; Neurologists ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is characterized by a rapid disease course, with disease severity being associated with declining health-related quality of life (HRQoL) in persons living with ALS (pALS). The main objective of this study was to assess the impact of disease progression on HRQoL across King's, Milano-Torino Staging (MiToS), and physician-judgement clinical staging. Additionally, we evaluated the impact of the disease on the HRQoL of care partners (cALS).

METHODS: Data were sourced from the Adelphi ALS Disease Specific Programme (DSP)™, a cross-sectional survey of neurologists, pALS and cALS presenting in a real-world clinical setting between July 2020 and March 2021 in Europe and the United States.

RESULTS: Neurologists (n = 142) provided data for 880 pALS. There were significant negative correlations between all three clinical staging systems and EuroQol (European Quality of Life) Five Dimension Five Level Scale (EQ-5D-5L) utility scores and visual analogue scale (VAS) ratings. Although not all differences were significant, 5-item Amyotrophic Lateral Sclerosis Assessment Questionnaire (ALSAQ-5) scores showed a stepwise increase in HRQoL impairment at each stage of the disease regardless of the staging system. At later stages, high levels of fatigue and substantial activity impairment were reported. As pALS disease states progressed, cALS also experienced a decline in HRQoL and increased burden.

CONCLUSIONS: Across outcomes, pALS and cALS generally reported worse outcomes at later stages of the disease, highlighting an unmet need in this population for strategies to maximise QoL despite disease progression. Recognition and treatment of symptoms such as pain and fatigue may lead to improved outcomes for pALS and cALS.}, } @article {pmid38198547, year = {2024}, author = {Perlegos, AE and Durkin, J and Belfer, SJ and Rodriguez, A and Shcherbakova, O and Park, K and Luong, J and Bonini, NM and Kayser, MS}, title = {TDP-43 impairs sleep in Drosophila through Ataxin-2-dependent metabolic disturbance.}, journal = {Science advances}, volume = {10}, number = {2}, pages = {eadj4457}, pmid = {38198547}, issn = {2375-2548}, support = {P30 AG010124/AG/NIA NIH HHS/United States ; T32 HL007953/HL/NHLBI NIH HHS/United States ; P40 OD018537/OD/NIH HHS/United States ; F31 AG063470/AG/NIA NIH HHS/United States ; T32 MH014654/MH/NIMH NIH HHS/United States ; R01 AG071777/AG/NIA NIH HHS/United States ; R56 AG071777/AG/NIA NIH HHS/United States ; R01 GM084947/GM/NIGMS NIH HHS/United States ; F30 AG058409/AG/NIA NIH HHS/United States ; P40 OD010949/OD/NIH HHS/United States ; F32 NS117785/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Humans ; *Amyotrophic Lateral Sclerosis ; Ataxin-2 ; DNA-Binding Proteins/genetics ; Drosophila ; *Neurodegenerative Diseases ; }, abstract = {Neurodegenerative diseases such as amyotrophic lateral sclerosis and frontotemporal dementia are associated with substantial sleep disruption, which may accelerate cognitive decline and brain degeneration. Here, we define a role for trans-activation response element (TAR) DNA binding protein 43 (TDP-43), a protein associated with human neurodegenerative disease, in regulating sleep using Drosophila. Expression of TDP-43 severely disrupts sleep, and the sleep deficit is rescued by Atx2 knockdown. Brain RNA sequencing revealed that Atx2 RNA interference regulates transcripts enriched for small-molecule metabolic signaling in TDP-43 brains. Focusing on these Atx2-regulated genes, we identified suppressors of the TDP-43 sleep phenotype enriched for metabolism pathways. Knockdown of Atx2 or treatment with rapamycin attenuated the sleep phenotype and mitigated the disruption of small-molecule glycogen metabolism caused by TDP-43. Our findings provide a connection between toxicity of TDP-43 and sleep disturbances and highlight key aspects of metabolism that interplay with TDP-43 toxicity upon Atx2 rescue.}, } @article {pmid38197966, year = {2024}, author = {Dzik, KP and Flis, DJ and Kaczor-Keller, KB and Bytowska, ZK and Karnia, MJ and Ziółkowski, W and Kaczor, JJ}, title = {Spinal cord abnormal autophagy and mitochondria energy metabolism are modified by swim training in SOD1-G93A mice.}, journal = {Journal of molecular medicine (Berlin, Germany)}, volume = {102}, number = {3}, pages = {379-390}, pmid = {38197966}, issn = {1432-1440}, support = {(2018/29/N/NZ7/01627)//Narodowe Centrum Nauki/ ; }, mesh = {Animals ; Mice ; *Amyotrophic Lateral Sclerosis/genetics/metabolism ; Autophagy ; Disease Models, Animal ; Energy Metabolism ; Insulin-Like Growth Factor I ; Mice, Transgenic ; Mitochondria/metabolism ; Motor Neurons/metabolism ; Superoxide Dismutase/genetics/metabolism ; Superoxide Dismutase-1/genetics/metabolism ; }, abstract = {Amyotrophic lateral sclerosis (ALS) may result from the dysfunctions of various mechanisms such as protein accumulation, mitophagy, and biogenesis of mitochondria. The purpose of the study was to evaluate the molecular mechanisms in ALS development and the impact of swim training on these processes. In the present study, an animal model of ALS, SOD1-G93A mice, was used with the wild-type mice as controls. Mice swam five times per week for 30 min. Mice were analyzed before ALS onset (70 days old), at ALS 1 disease onset (116 days old), and at the terminal stage of the disease ALS (130 days old), and compared with the corresponding ALS untrained groups and normalized to the wild-type group. Enzyme activity and protein content were analyzed in the spinal cord homogenates. The results show autophagy disruptions causing accumulation of p62 accompanied by low PGC-1α and IGF-1 content in the spinal cord of SOD1-G93A mice. Swim training triggered a neuroprotective effect, attenuation of NF-l degradation, less accumulated p62, and lower autophagy initiation. The IGF-1 pathway induces pathophysiological adaptation to maintain energy demands through anaerobic metabolism and mitochondrial protection. KEY MESSAGES: The increased protein content of p62 in the spinal cord of SOD1-G93A mice suggests that autophagic clearance and transportation are disrupted. Swim training attenuates neurofilament light destruction in the spinal cord of SOD1-G93A mice. Swim training reducing OGDH provokes suppression of ATP-consuming anabolic pathways. Swim training induces energy metabolic changes and mitochondria protection through the IGF-1 signaling pathway.}, } @article {pmid38197897, year = {2024}, author = {Iguchi, Y and Takahashi, Y and Li, J and Araki, K and Amakusa, Y and Kawakami, Y and Kobayashi, K and Yokoi, S and Katsuno, M}, title = {IκB kinase phosphorylates cytoplasmic TDP-43 and promotes its proteasome degradation.}, journal = {The Journal of cell biology}, volume = {223}, number = {2}, pages = {}, pmid = {38197897}, issn = {1540-8140}, support = {JP20H03589//Japan Society for the Promotion of Science/ ; JP21wm0425013//Japan Agency for Medical Research and Development/ ; //SERIKA/ ; //Japan ALS Association/ ; //Takeda Science Foundation/ ; }, mesh = {Animals ; Mice ; *Amyotrophic Lateral Sclerosis/genetics ; Disease Models, Animal ; *DNA-Binding Proteins/genetics ; *Frontotemporal Dementia ; *Frontotemporal Lobar Degeneration ; *I-kappa B Kinase/genetics ; Proteasome Endopeptidase Complex ; Humans ; }, abstract = {Cytoplasmic aggregation of TDP-43 in neurons is a pathological feature common to amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). We demonstrate that the IκB kinase (IKK) complex promotes the degradation of cytoplasmic TDP-43 through proteasomes. While IKKβ is a major factor in TDP-43 degradation, IKKα acts as a cofactor, and NEMO functions as a scaffold for the recruitment of TDP-43 to the IKK complex. Furthermore, we identified IKKβ-induced phosphorylation sites of TDP-43 and found that phosphorylation at Thr8 and Ser92 is important for the reduction of TDP-43 by IKK. TDP-43 phosphorylation at Ser92 was detected in a pattern different from that of C-terminal phosphorylation in the pathological inclusion of ALS. IKKβ was also found to significantly reduce the expression level and toxicity of the disease-causing TDP-43 mutation. Finally, the favorable effect of IKKβ on TDP-43 aggregation was confirmed in the hippocampus of mice. IKK and the N-terminal phosphorylation of TDP-43 are potential therapeutic targets for ALS and FTLD.}, } @article {pmid38196621, year = {2023}, author = {Pottinger, TD and Motelow, JE and Povysil, G and Moreno, CAM and Ren, Z and Phatnani, H and , and Aitman, TJ and Santoyo-Lopez, J and , and Mitsumoto, H and , and Goldstein, DB and Harms, MB}, title = {Rare variant analyses validate known ALS genes in a multi-ethnic population and identifies ANTXR2 as a candidate in PLS.}, journal = {Research square}, volume = {}, number = {}, pages = {}, pmid = {38196621}, issn = {2693-5015}, support = {K01 MH098126/MH/NIMH NIH HHS/United States ; MC_PC_15080/MRC_/Medical Research Council/United Kingdom ; RC2 MH089915/MH/NIMH NIH HHS/United States ; P01 HD080642/HD/NICHD NIH HHS/United States ; R01 MH097971/MH/NIMH NIH HHS/United States ; RC2 NS070344/NS/NINDS NIH HHS/United States ; UL1 TR000040/TR/NCATS NIH HHS/United States ; UL1 TR001873/TR/NCATS NIH HHS/United States ; UM1 AI100645/AI/NIAID NIH HHS/United States ; P30 AG028377/AG/NIA NIH HHS/United States ; U54 NS078059/NS/NINDS NIH HHS/United States ; P01 AG007232/AG/NIA NIH HHS/United States ; RF1 AG054023/AG/NIA NIH HHS/United States ; R01 HD048805/HD/NICHD NIH HHS/United States ; U01 HG007672/HG/NHGRI NIH HHS/United States ; U01 NS053998/NS/NINDS NIH HHS/United States ; U01 NS077303/NS/NINDS NIH HHS/United States ; U19 AI067854/AI/NIAID NIH HHS/United States ; R01 AG037212/AG/NIA NIH HHS/United States ; R01 ES016348/ES/NIEHS NIH HHS/United States ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease affecting over 30,000 people in the United States. It is characterized by the progressive decline of the nervous system that leads to the weakening of muscles which impacts physical function. Approximately, 15% of individuals diagnosed with ALS have a known genetic variant that contributes to their disease. As therapies that slow or prevent symptoms, such as antisense oligonucleotides, continue to develop, it is important to discover novel genes that could be targets for treatment. Additionally, as cohorts continue to grow, performing analyses in ALS subtypes, such as primary lateral sclerosis (PLS), becomes possible due to an increase in power. These analyses could highlight novel pathways in disease manifestation.

METHODS: Building on our previous discoveries using rare variant association analyses, we conducted rare variant burden testing on a substantially larger cohort of 6,970 ALS patients from a large multi-ethnic cohort as well as 166 PLS patients, and 22,524 controls. We used intolerant domain percentiles based on sub-region Residual Variation Intolerance Score (subRVIS) that have been described previously in conjunction with gene based collapsing approaches to conduct burden testing to identify genes that associate with ALS and PLS.

RESULTS: A gene based collapsing model showed significant associations with SOD1, TARDBP, and TBK1 (OR=19.18, p = 3.67 × 10[-39]; OR=4.73, p = 2 × 10[-10]; OR=2.3, p = 7.49 × 10[-9], respectively). These genes have been previously associated with ALS. Additionally, a significant novel control enriched gene, ALKBH3 (p = 4.88 × 10[-7]), was protective for ALS in this model. An intolerant domain based collapsing model showed a significant improvement in identifying regions in TARDBP that associated with ALS (OR=10.08, p = 3.62 × 10[-16]). Our PLS protein truncating variant collapsing analysis demonstrated significant case enrichment in ANTXR2 (p=8.38 × 10[-6]).

CONCLUSIONS: In a large multi-ethnic cohort of 6,970 ALS patients, rare variant burden testing validated known ALS genes and identified a novel potentially protective gene, ALKBH3. A first-ever analysis in 166 patients with PLS found a candidate association with loss-of-function mutations in ANTXR2.}, } @article {pmid38196030, year = {2024}, author = {Mohammadi, S and Seyedalipour, B and Hashemi, SZ and Hosseinkhani, S and Mohseni, M}, title = {Implications of ALS-Associated Mutations on Biochemical and Biophysical Features of hSOD1 and Aggregation Formation.}, journal = {Biochemical genetics}, volume = {62}, number = {5}, pages = {3658-3680}, pmid = {38196030}, issn = {1573-4927}, mesh = {*Amyotrophic Lateral Sclerosis/genetics/metabolism ; Humans ; *Superoxide Dismutase-1/genetics/metabolism/chemistry ; *Mutation ; Amyloid/metabolism ; Protein Aggregates ; Protein Aggregation, Pathological/genetics ; }, abstract = {One of the recognized motor neuron degenerative disorders is amyotrophic lateral sclerosis (ALS). By now, several mutations have been reported and linked to ALS patients, some of which are induced by mutations in the human superoxide dismutase (hSOD1) gene. The ALS-provoking mutations are located throughout the structure of hSOD1 and promote the propensity to aggregate. Despite numerous investigations, the underlying mechanism related to the toxicity of mutant hSOD1 through the gain of a toxic function is still vague. We surveyed two mutant forms of hSOD1 by removing and adding cysteine at positions 146 and 72, respectively, to investigate the biochemical characterization and amyloid formation. Our findings predicted the harmful and destabilizing impact of two SOD1 mutants using multiple programs. The specific activity of the wild-type form was about 1.42- and 1.92-fold higher than that of C146R and G72C mutants, respectively. Comparative structural studies using CD spectropolarimetry, and intrinsic and ANS fluorescence showed alterations in secondary structure content, exposure of hydrophobic patches, and structural compactness of WT-hSOD1 vs. mutants. We demonstrated that two mutants were able to promote amyloid-like aggregates under amyloid induction circumstances (50-mM Tris-HCl pH 7.4, 0.2-M KSCN, 50-mM DTT, 37 °C, 190 rpm). Monitoring aggregates were done using an enhancement in thioflavin T fluorescence and alterations in Congo red absorption. The mutants accelerated fibrillation with subsequently greater fluorescence amplitude and a shorter lag time compared to WT-SOD1. These findings support the aggregation of ALS-associated SOD1 mutants as an integral part of ALS pathology.}, } @article {pmid38195712, year = {2024}, author = {Ravichandran, KA and Heneka, MT}, title = {Inflammasomes in neurological disorders - mechanisms and therapeutic potential.}, journal = {Nature reviews. Neurology}, volume = {20}, number = {2}, pages = {67-83}, pmid = {38195712}, issn = {1759-4766}, mesh = {Humans ; Inflammasomes/metabolism ; *Nervous System Diseases/drug therapy ; *Stroke ; *Multiple Sclerosis ; Brain/metabolism ; }, abstract = {Inflammasomes are molecular scaffolds that are activated by damage-associated and pathogen-associated molecular patterns and form a key element of innate immune responses. Consequently, the involvement of inflammasomes in several diseases that are characterized by inflammatory processes, such as multiple sclerosis, is widely appreciated. However, many other neurological conditions, including Alzheimer disease, Parkinson disease, amyotrophic lateral sclerosis, stroke, epilepsy, traumatic brain injury, sepsis-associated encephalopathy and neurological sequelae of COVID-19, all involve persistent inflammation in the brain, and increasing evidence suggests that inflammasome activation contributes to disease progression in these conditions. Understanding the biology and mechanisms of inflammasome activation is, therefore, crucial for the development of inflammasome-targeted therapies for neurological conditions. In this Review, we present the current evidence for and understanding of inflammasome activation in neurological diseases and discuss current and potential interventional strategies that target inflammasome activation to mitigate its pathological consequences.}, } @article {pmid38194904, year = {2024}, author = {Nassar, J and Rizk, C and Fares, G and Tohme, C and Braidy, C and Farah, J}, title = {Clinical image quality assessment and mean glandular dose for full field digital mammography.}, journal = {Journal of radiological protection : official journal of the Society for Radiological Protection}, volume = {44}, number = {1}, pages = {}, doi = {10.1088/1361-6498/ad1cd4}, pmid = {38194904}, issn = {1361-6498}, mesh = {Humans ; Female ; Radiation Dosage ; Retrospective Studies ; Mammography ; *Radiation Exposure ; Diagnostic Reference Levels ; *Breast Neoplasms/diagnostic imaging ; Radiographic Image Enhancement/methods ; }, abstract = {This study aims to assess the image quality (IQ) of 12 mammographic units and to identify units with potential optimisation needs. Data for 350 mammography examinations meeting inclusion criteria were collected retrospectively from April 2021 to April 2022. They were categorised based on the medical reports into 10 normal cases, 10 cases displaying calcifications and 10 cases presenting lesions. Two radiologists assessed the IQ of 1400 mammograms, evaluating system performance per Boitaet al's study and positioning performance following European guidelines. To measure agreement between the two radiologists, the Cohen's Kappa coefficient (κ) was computed, quantifying the excess of agreement beyond chance. The visual grading analysis score (VGAS) was computed to compare system and positioning performance assessments across different categories and facilities. Median average glandular dose (AGD) values for cranio caudal and medio lateral oblique views were calculated for each category and facility and compared to the national diagnostic reference levels. The health facilities were categorised by considering both IQ VGAS and AGD levels. Inter-rater agreement between radiologists ranged from poor (κ< 0.20) to moderate (0.41 <κ< 0.60), likely influenced by inherent biases and distinct IQ expectations. 50% of the facilities were classified as needing corrective actions for their system performance as they had IQ or high AGD that could increase recall rate and radiation risk and 50% of the health facilities exhibited insufficient positioning performance that could mask tumour masses and microcalcifications. The study's findings emphasise the importance of implementing quality assurance programs to ensure optimal IQ for accurate diagnoses while adhering to radiation exposure guidelines. Additionally, comprehensive training for technologists is essential to address positioning challenges. These initiatives collectively aim to enhance the overall quality of breast imaging services, contributing to improved patient care.}, } @article {pmid38194198, year = {2024}, author = {Xu, A and Luo, Y and Tang, Y and Yang, F and Gao, X and Qiao, G and Zhu, X and Zhou, J}, title = {Chitinases as a potential diagnostic and prognostic biomarker for amyotrophic lateral sclerosis: a systematic review and meta-analysis.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {45}, number = {6}, pages = {2489-2503}, pmid = {38194198}, issn = {1590-3478}, support = {2023AFD128//Hubei Provincial Natural Science Foundation and the Innovation and Development of Traditional Chinese Medicine of China/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/cerebrospinal fluid/diagnosis/blood ; Humans ; *Biomarkers/cerebrospinal fluid/blood ; *Chitinases/cerebrospinal fluid/blood ; Prognosis ; Hexosaminidases/cerebrospinal fluid/blood ; Chitinase-3-Like Protein 1/cerebrospinal fluid/blood ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the degeneration of motor neurons, and there is currently a lack of reliable diagnostic biomarkers. This meta-analysis aimed to evaluate CHIT1, CHI3L1, and CHI3L2 levels in the cerebrospinal fluid (CSF) or blood and their diagnostic potential in ALS patients. A systematic, comprehensive search was performed of peer-reviewed English-language articles published before April 1, 2023, in PubMed, Scopus, Embase, Cochrane Library, and Web of Science. After a thorough screening, 13 primary articles were included, and their chitinases-related data were extracted for systematic review and meta-analysis. In ALS patients, the CSF CHIT1 levels were significantly elevated compared to controls with healthy control (HC) (SMD, 1.92; 95% CI, 0.78 - 3.06; P < 0.001). CHIT1 levels were elevated in the CSF of ALS patients compared to other neurodegenerative diseases (ONDS) control (SMD, 0.74; 95% CI, 0.22 - 1.27; P < 0.001) and exhibited an even more substantial increase when compared to ALS-mimicking diseases (AMDS) (SMD, 1.15; 95% CI, 0.35 - 1.94, P < 0.001). Similarly, the CSF CHI3L1 levels were significantly higher in ALS patients compared to HC (SMD, 3.16; 95% CI, 1.26 - 5.06, P < 0.001). CHI3L1 levels were elevated in the CSF of ALS patients compared to ONDS (SMD, 0.75; 95% CI, 0.32 - 1.19; P = 0.017) and exhibited a more pronounced increase when compared to AMDS (SMD, 1.92; 95% CI, 0.41 - 3.42; P < 0.001). The levels of CSF chitinases in the ALS patients showed a significant increase, supporting the role of CSF chitinases as diagnostic biomarkers for ALS.}, } @article {pmid38194085, year = {2024}, author = {Zhu, L and Deng, F and Bai, D and Hou, J and Jia, Q and Zhang, C and Ou, K and Li, S and Li, XJ and Yin, P}, title = {Loss of TDP-43 mediates severe neurotoxicity by suppressing PJA1 gene transcription in the monkey brain.}, journal = {Cellular and molecular life sciences : CMLS}, volume = {81}, number = {1}, pages = {16}, pmid = {38194085}, issn = {1420-9071}, support = {32270564//National Natural Science Foundation of China/ ; 81830032//National Natural Science Foundation of China/ ; 82071421//National Natural Science Foundation of China/ ; 2023A1515010811//Guangdong Basic and Applied Basic Research/ ; 2022A1515011205//Guangdong Basic and Applied Basic Research/ ; 2021ZT09Y007//Department of Science and Technology of Guangdong Province/ ; 2018B030337001//Department of Science and Technology of Guangdong Province/ ; 202007030008//Guangzhou Key Research Program on Brain Science/ ; 21622113//Fundamental Research Funds for the Central Universities/ ; }, mesh = {Animals ; *Amyotrophic Lateral Sclerosis/genetics ; *Brain ; *DNA-Binding Proteins/genetics ; Haplorhini ; Transcription, Genetic ; *Ubiquitin-Protein Ligases/genetics ; Disease Models, Animal ; }, abstract = {The nuclear loss and cytoplasmic accumulation of TDP-43 (TAR DNA/RNA binding protein 43) are pathological hallmarks of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Previously, we reported that the primate-specific cleavage of TDP-43 accounts for its cytoplasmic mislocalization in patients' brains. This prompted us to investigate further whether and how the loss of nuclear TDP-43 mediates neuropathology in primate brain. In this study, we report that TDP-43 knockdown at the similar effectiveness, induces more damage to neuronal cells in the monkey brain than rodent mouse. Importantly, the loss of TDP-43 suppresses the E3 ubiquitin ligase PJA1 expression in the monkey brain at transcriptional level, but yields an opposite upregulation of PJA1 in the mouse brain. This distinct effect is due to the species-dependent binding of nuclear TDP-43 to the unique promoter sequences of the PJA1 genes. Further analyses reveal that the reduction of PJA1 accelerates neurotoxicity, whereas overexpressing PJA1 diminishes neuronal cell death by the TDP-43 knockdown in vivo. Our findings not only uncover a novel primate-specific neurotoxic contribution to the loss of function theory of TDP-43 proteinopathy, but also underscore a potential therapeutic approach of PJA1 to the loss of nuclear TDP-43.}, } @article {pmid38193795, year = {2024}, author = {Corrales-Guerrero, L and Díaz-Moreno, I}, title = {Deciphering the role of Zn[2+]-binding histidines from TIA-1 on the assembly and dynamics of stress granules.}, journal = {BioFactors (Oxford, England)}, volume = {50}, number = {4}, pages = {750-755}, doi = {10.1002/biof.2037}, pmid = {38193795}, issn = {1872-8081}, support = {DOC_00796//Agencia de Innovación y Desarrollo de Andalucía/ ; P18-FR-3487//Agencia de Innovación y Desarrollo de Andalucía/ ; PID2021-126663NB-I00//Ministerio de Ciencia e Innovación/ ; }, mesh = {*T-Cell Intracellular Antigen-1/metabolism/genetics ; *Zinc/metabolism ; *Histidine/metabolism/genetics/chemistry ; *Stress Granules/metabolism/genetics ; Humans ; Protein Binding ; Binding Sites ; Cytoplasmic Granules/metabolism/genetics ; }, abstract = {T-cell intracellular antigen-1 (TIA-1) is a key RNA-binding protein that participates in translation regulation and RNA splicing. TIA-1 undergoes liquid-liquid phase separation as a fundamental mechanism that enables the condensation of RNA and proteins into membraneless organelles called stress granules (SGs). However, this dynamic behavior can lead to aberrant fibril formation, implicated in neurodegenerative disorders, and must be tightly regulated. In this study, we investigated the role in the cell of histidine residues His94 and His96, responsible for Zn[2+] binding. Using fluorescence microscopy, we found that the specific binding site formed by these residues is critical for SG assembly. Furthermore, it also plays a role maintaining the dynamic behavior of SG-assembled TIA-1. Collectively, our findings confirm the physiological relevance of TIA-1 His94 and His96 in the Zn[2+]-mediated regulatory mechanism for protection against fibril formation in SGs.}, } @article {pmid38193356, year = {2024}, author = {Tsuji, K and Nakayama, Y and Taruya, J and Ito, H}, title = {Persistence of Kii amyotrophic lateral sclerosis after the 2000s and its characteristic aging-related tau astrogliopathy.}, journal = {Journal of neuropathology and experimental neurology}, volume = {83}, number = {2}, pages = {79-93}, doi = {10.1093/jnen/nlad113}, pmid = {38193356}, issn = {1554-6578}, support = {18H02743//Japan Society for the Promotion of Science/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/pathology ; Brain/pathology ; *Dementia/pathology ; Japan/epidemiology ; *Parkinsonian Disorders ; Tauopathies/pathology ; TDP-43 Proteinopathies/pathology ; }, abstract = {Kii amyotrophic lateral sclerosis (ALS) is a unique disease that occurs in the southern portion of the Kii Peninsula and exhibits a dual pathology of TAR DNA-binding protein of 43 kDa (TDP-43) proteinopathy and tauopathy. The incidence of ALS in this region was very high in the 1960s, briefly decreased through the 1980s, but began increasing again after 2000 with a change of high-concentration geographic foci. It is unclear, however, whether the unique pathological features have changed along with the incidence changes. This study analyzed postmortem specimens from neuropathologically confirmed Kii ALS cases from the 1970s (n = 4) and those after 1999 (n = 12) from the southern Kii Peninsula or outside of the area. Our results confirm the continued occurrence of Kii ALS after 2000 in the southern Kii Peninsula and the preservation of disease-specific neuronal tau pathology, including the widespread occurrence throughout the brain and spinal cord, sparse neuropil threads, and predominance in superficial layers. Furthermore, we assessed the glial tau pathology of Kii and non-Kii ALS in accordance with the aging-related tau astrogliopathy classification method for the first time and detected a unique brainstem predominant appearance of gray matter aging-related tau astrogliopathy in Kii ALS cases, which may provide clues to pathogenetic mechanisms.}, } @article {pmid38191942, year = {2024}, author = {Hernandez-Candia, CN and Brady, BR and Harrison, E and Tucker, CL}, title = {A platform to induce and mature biomolecular condensates using chemicals and light.}, journal = {Nature chemical biology}, volume = {20}, number = {4}, pages = {452-462}, pmid = {38191942}, issn = {1552-4469}, support = {R21 MH134019/MH/NIMH NIH HHS/United States ; R35 GM136367/GM/NIGMS NIH HHS/United States ; }, mesh = {Humans ; *Biomolecular Condensates ; *Huntington Disease/genetics ; Optogenetics ; Proteostasis ; }, abstract = {Biomolecular condensates are membraneless compartments that impart spatial and temporal organization to cells. Condensates can undergo maturation, transitioning from dynamic liquid-like states into solid-like states associated with neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and Huntington's disease. Despite their important roles, many aspects of condensate biology remain incompletely understood, requiring tools for acutely manipulating condensate-relevant processes within cells. Here we used the BCL6 BTB domain and its ligands BI-3802 and BI-3812 to create a chemical genetic platform, BTBolig, allowing inducible condensate formation and dissolution. We also developed optogenetic and chemical methods for controlled induction of condensate maturation, where we surprisingly observed recruitment of chaperones into the condensate core and formation of dynamic biphasic condensates. Our work provides insights into the interaction of condensates with proteostasis pathways and introduces a suite of chemical-genetic approaches to probe the role of biomolecular condensates in health and disease.}, } @article {pmid38191789, year = {2024}, author = {Salomonsson, SE and Maltos, AM and Gill, K and Aladesuyi Arogundade, O and Brown, KA and Sachdev, A and Sckaff, M and Lam, KJK and Fisher, IJ and Chouhan, RS and Van Laar, VS and Marley, CB and McLaughlin, I and Bankiewicz, KS and Tsai, YC and Conklin, BR and Clelland, CD}, title = {Validated assays for the quantification of C9orf72 human pathology.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {828}, pmid = {38191789}, issn = {2045-2322}, support = {K08 NS112330/NS/NINDS NIH HHS/United States ; U19 NS132303/NS/NINDS NIH HHS/United States ; TL1 TR001871/TR/NCATS NIH HHS/United States ; R01 HL130533/HL/NHLBI NIH HHS/United States ; AACSF-17-531484/ALZ/Alzheimer's Association/United States ; RF1 AG072052/AG/NIA NIH HHS/United States ; R01 AG072052/AG/NIA NIH HHS/United States ; U01 NS134062/NS/NINDS NIH HHS/United States ; P01 HL146366/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; Mice ; Humans ; *Amyotrophic Lateral Sclerosis/genetics ; C9orf72 Protein/genetics ; *Frontotemporal Dementia ; Antibodies ; *Craniocerebral Trauma ; Mice, Transgenic ; DNA ; RNA ; }, abstract = {A repeat expansion mutation in the C9orf72 gene is the leading known genetic cause of FTD and ALS. The C9orf72-ALS/FTD field has been plagued by a lack of reliable tools to monitor this genomic locus and its RNA and protein products. We have validated assays that quantify C9orf72 pathobiology at the DNA, RNA and protein levels using knock-out human iPSC lines as controls. Here we show that single-molecule sequencing can accurately measure the repeat expansion and faithfully report on changes to the C9orf72 locus in what has been a traditionally hard to sequence genomic region. This is of particular value to sizing and phasing the repeat expansion and determining changes to the gene locus after gene editing. We developed ddPCR assays to quantify two major C9orf72 transcript variants, which we validated by selective excision of their distinct transcriptional start sites. Using validated knock-out human iPSC lines, we validated 4 commercially available antibodies (of 9 tested) that were specific for C9orf72 protein quantification by Western blot, but none were specific for immunocytochemistry. We tested 15 combinations of antibodies against dipeptide repeat proteins (DPRs) across 66 concentrations using MSD immunoassay, and found two (against poly-GA and poly-GP) that yielded a 1.5-fold or greater signal increase in patient iPSC-motor neurons compared to knock-out control, and validated them in human postmortem and transgenic mouse brain tissue. Our validated DNA, RNA and protein assays are applicable to discovery research as well as clinical trials.}, } @article {pmid38189756, year = {2024}, author = {Zeng, Y and Cao, S and Pang, K and Tang, J and Lin, G}, title = {Causal Association Between Sepsis and Neurodegenerative Diseases: A Bidirectional Two-Sample Mendelian Randomization Study.}, journal = {Journal of Alzheimer's disease : JAD}, volume = {97}, number = {1}, pages = {229-237}, doi = {10.3233/JAD-230954}, pmid = {38189756}, issn = {1875-8908}, mesh = {Humans ; *Neurodegenerative Diseases/complications/epidemiology/genetics ; *Alzheimer Disease/genetics ; Genome-Wide Association Study ; Mendelian Randomization Analysis ; Reproducibility of Results ; *Sepsis/complications/genetics ; }, abstract = {BACKGROUND: Previous observational studies suggested an association between sepsis and neurodegenerative diseases, but causality remains unclear.

OBJECTIVE: Determining the causal association between sepsis and four neurodegenerative diseases (Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Lewy body dementia) through bidirectional two-sample Mendelian randomization (MR) analysis.

METHODS: Genome-wide association study summary statistics for all traits were obtained from publicly available databases. Inverse variance weighted (IVW) was the primary method for evaluating causal associations. In addition, three additional MR methods (MR-Egger, weighted median, and maximum likelihood method) were employed to supplement IVW. Furthermore, various sensitivity tests were conducted to assess the reliability: 1) Cochrane's Q test for assessing heterogeneity; 2) MR-Egger intercept test and MR-PRESSO global test for evaluating horizontal pleiotropy; 3) leave-one-out sensitivity test for determining the stability.

RESULTS: The results of IVW indicated that sepsis significantly increased the risk of Alzheimer's disease (OR = 1.11, 95% CI: 1.01-1.21, p = 0.025). In addition, three additional MR methods suggested parallel results. However, no causal effect of sepsis on the three other neurodegenerative diseases was identified. Subsequently, reverse MR analysis indicated that the four neurodegenerative diseases do not causally affect sepsis. Furthermore, sensitivity tests demonstrated the reliability of the MR analyses, suggesting no heterogeneity or horizontal pleiotropy.

CONCLUSIONS: The present study contributes to a deeper comprehension of the intricate interplay between sepsis and neurodegenerative disorders, thereby offering potential avenues for the development of therapeutic agents that can effectively mitigate the multifarious complications associated with sepsis.}, } @article {pmid38189364, year = {2025}, author = {Lim, SJ and Muhd Noor, ND and Sabri, S and Mohamad Ali, MS and Salleh, AB and Oslan, SN}, title = {Features of the rare pathogen Meyerozyma guilliermondii strain SO and comprehensive in silico analyses of its adherence-contributing virulence factor agglutinin-like sequences.}, journal = {Journal of biomolecular structure & dynamics}, volume = {43}, number = {7}, pages = {3728-3748}, doi = {10.1080/07391102.2023.2300757}, pmid = {38189364}, issn = {1538-0254}, mesh = {*Virulence Factors/chemistry/metabolism/genetics ; Biofilms/growth & development ; Fungal Proteins/chemistry/metabolism/genetics ; Animals ; Virulence ; Amino Acid Sequence ; Zebrafish ; *Saccharomycetales/pathogenicity/metabolism ; Computer Simulation ; Molecular Docking Simulation ; }, abstract = {Meyerozyma guilliermondii is a rare yeast pathogen contributing to the deadly invasive candidiasis. M. guilliermondii strain SO, as a promising protein expression host, showed 99% proteome similarity with the clinically isolated ATCC 6260 (type strain) in a recent comparative genomic analysis. However, their in vitro virulence features and in vivo pathogenicity were uncharacterized. This study aimed to characterize the in vitro and in vivo pathogenicity of M. guilliermondii strain SO and analyze its Als proteins (MgAls) via comprehensive bioinformatics approaches. M. guilliermondii strain SO showed lower and higher sensitivity towards β-mercaptoethanol and lithium, respectively than the avirulent S. cerevisiae but exhibited the same tolerance towards cell wall-perturbing Congo Red with C. albicans. With 7.5× higher biofilm mass, M. guilliermondii strain SO also demonstrated 75% higher mortality rate in the zebrafish embryos with a thicker biofilm layer on the chorion compared to the avirulent S. cerevisiae. Being one of the most important Candida adhesins, sequence and structural analyses of four statistically identified MgAls showed that MgAls1056 was predicted to exhibit the most conserved amyloid-forming regions, tandem repeat domain and peptide binding cavity (PBC) compared to C. albicans Als3. Favoured from the predicted largest ligand binding site and druggable pockets, it showed the highest affinity towards hepta-threonine. Non-PBC druggable pockets in the most potent virulence contributing MgAls1056 provide new insights into developing antifungal drugs targeting non-albicans Candida spp. Virtual screening of available synthetic or natural bioactive compounds and MgAls1056 deletion from the fungal genome should be further performed and validated experimentally.}, } @article {pmid38189033, year = {2023}, author = {Moreno-Roco, J and Del Valle, L and Jiménez, D and Acosta, I and Castillo, JL and Dharmadasa, T and Kiernan, MC and Matamala, JM}, title = {Diagnostic utility of transcranial magnetic stimulation for neurodegenerative disease: a critical review.}, journal = {Dementia & neuropsychologia}, volume = {17}, number = {}, pages = {e20230048}, pmid = {38189033}, issn = {1980-5764}, abstract = {Neurodegenerative diseases pose significant challenges due to their impact on brain structure, function, and cognition. As life expectancy rises, the prevalence of these disorders is rapidly increasing, resulting in substantial personal, familial, and societal burdens. Efforts have been made to optimize the diagnostic and therapeutic processes, primarily focusing on clinical, cognitive, and imaging characterization. However, the emergence of non-invasive brain stimulation techniques, specifically transcranial magnetic stimulation (TMS), offers unique functional insights and diagnostic potential. TMS allows direct evaluation of brain function, providing valuable information inaccessible through other methods. This review aims to summarize the current and potential diagnostic utility of TMS in investigating neurodegenerative diseases, highlighting its relevance to the field of cognitive neuroscience. The findings presented herein contribute to the growing body of research focused on improving our understanding and management of these debilitating conditions, particularly in regions with limited resources and a pressing need for innovative approaches.}, } @article {pmid38188422, year = {2023}, author = {Doyle, JJ and Parker, JA}, title = {Genetic Interactions of Progranulin Across the ALS-FTD Spectrum and Beyond.}, journal = {microPublication biology}, volume = {2023}, number = {}, pages = {}, pmid = {38188422}, issn = {2578-9430}, support = {P40 OD010440/OD/NIH HHS/United States ; }, abstract = {Progranulin (PGRN) is a growth factor in which mutations are one of the leading causes of frontotemporal dementia (FTD), and has been implicated in an assortment of neurodegenerative diseases. Conversely, higher levels of the protein have shown potential as a general neuronal protective factor. While examining its neuroprotective applications on a broader scale would be unfeasible in mammalian models, we turned to the nematode C. elegans to map the interactions of PGRN across multiple genetic models of neurodegenerative diseases. Our results indicate that while the overexpression of PGRN appears to be protective across all models tested, the loss of PGRN exacerbated the disease phenotypes of all but three of the models tested. Given the ease of genetic analysis in nematodes, we propose this model organism as an efficient tool to build a comprehensive map of PGRN's genetic interactions.}, } @article {pmid38188233, year = {2023}, author = {Lockard, G and Gordon, J and Schimmel, S and Sayed, BE and Monsour, M and Garbuzova-Davis, S and Borlongan, CV}, title = {Attenuation of amyotrophic lateral sclerosis via stem cell and extracellular vesicle therapy: An updated review.}, journal = {Neuroprotection}, volume = {1}, number = {2}, pages = {130-138}, pmid = {38188233}, issn = {2770-730X}, support = {R21 NS132576/NS/NINDS NIH HHS/United States ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a rapidly fatal neurological disease characterized by upper and lower motor neuron degeneration. Though typically idiopathic, familial forms of ALS are commonly comprised of a superoxide dismutase 1 (SOD1) mutation. Basic science frequently utilizes SOD1 models in vitro and in vivo to replicate ALS conditions. Therapies are sparse; those that exist on the market extend life minimally, thus driving the demand for research to identify novel therapeutics. Transplantation of stem cells is a promising approach for many diseases and has shown efficacy in SOD1 models and clinical trials. The underlying mechanism for stem cell therapy presents an exciting venue for research investigations. Most notably, the paracrine actions of stem cell-derived extracellular vesicles (EVs) have been suggested as a potent mitigating factor. This literature review focuses on the most recent preclinical research investigating cell-free methods for treating ALS. Various avenues are being explored, differing on the EV contents (protein, microRNA, etc.) and on the cell target (astrocyte, endothelial cell, motor neuron-like cells, etc.), and both molecular and behavioral outcomes are being examined. Unfortunately, EVs may also play a role in propagating ALS pathology. Nonetheless, the overarching goal remains clear; to identify efficient cell-free techniques to attenuate the deadly consequences of ALS.}, } @article {pmid38188146, year = {2024}, author = {Shao, BZ and Jiang, JJ and Zhao, YC and Zheng, XR and Xi, N and Zhao, GR and Huang, XW and Wang, SL}, title = {Neutrophil extracellular traps in central nervous system (CNS) diseases.}, journal = {PeerJ}, volume = {12}, number = {}, pages = {e16465}, pmid = {38188146}, issn = {2167-8359}, mesh = {Humans ; *Extracellular Traps ; *Central Nervous System Diseases ; *Multiple Sclerosis ; Central Nervous System ; Neutrophils ; }, abstract = {Excessive induction of inflammatory and immune responses is widely considered as one of vital factors contributing to the pathogenesis and progression of central nervous system (CNS) diseases. Neutrophils are well-studied members of inflammatory and immune cell family, contributing to the innate and adaptive immunity. Neutrophil-released neutrophil extracellular traps (NETs) play an important role in the regulation of various kinds of diseases, including CNS diseases. In this review, current knowledge on the biological features of NETs will be introduced. In addition, the role of NETs in several popular and well-studied CNS diseases including cerebral stroke, Alzheimer's disease, multiple sclerosis, amyotrophic lateral sclerosis (ALS), and neurological cancers will be described and discussed through the reviewing of previous related studies.}, } @article {pmid38188028, year = {2023}, author = {Hu, Z and Zuo, C and Mao, C and Shi, C and Xu, Y}, title = {Peripheral immune markers and amyotrophic lateral sclerosis: a Mendelian randomization study.}, journal = {Frontiers in neuroscience}, volume = {17}, number = {}, pages = {1269354}, pmid = {38188028}, issn = {1662-4548}, abstract = {INTRODUCTION: The peripheral immune system changes in amyotrophic lateral sclerosis (ALS), but the causal relationship between the two is still controversial.

METHODS: In this study, we aimed to estimate the causal relationship between peripheral immune markers and ALS using a two-sample Mendelian randomization method. Genome-wide association study (GWAS) data on peripheral blood immune traits from European populations were used for exposure, and ALS summary statistics were used as the outcome. The causal relationship was evaluated by inverse variance weighting, MR-Egger, and weighted median methods and verified by multiple sensitivity analysis.

RESULTS: We found that the increase of one standard deviation of lymphocyte count is related to reducing ALS risk. CD3 on effector memory CD4[+] T cell, HLA DR[+] CD4[+] T cell, effector memory CD8[+] T cell, terminally differentiated CD8[+] T cell and CD28- CD8[+] T cell is also a protective factor for ALS. Among the circulating immune protein, the increase of one standard deviation of α-2-macroglobulin receptor-associated protein (α-2-MRAP) and C4b showed associated with low risk of ALS, while Interleukin-21 (IL-21) increases the risk of ALS.

DISCUSSION: Our study further reveals the important role of peripheral immune activity in ALS.}, } @article {pmid38188011, year = {2023}, author = {Ansari, U and Chen, V and Sedighi, R and Syed, B and Muttalib, Z and Ansari, K and Ansari, F and Nadora, D and Razick, D and Lui, F}, title = {Role of the UNC13 family in human diseases: A literature review.}, journal = {AIMS neuroscience}, volume = {10}, number = {4}, pages = {388-400}, pmid = {38188011}, issn = {2373-7972}, abstract = {This literature review explores the pivotal roles of the Uncoordinated-13 (UNC13) protein family, encompassing UNC13A, UNC13B, UNC13C, and UNC13D, in the pathogenesis of various human diseases. These proteins, which are evolutionarily conserved and crucial for synaptic vesicle priming and exocytosis, have been implicated in a range of disorders, spanning from neurodegenerative diseases like amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) to immune-related conditions such as familial hemophagocytic lymphohistiocytosis (FHL). The involvement of UNC13A in neurotransmitter release and synaptic plasticity is linked to ALS and FTD, with genetic variations affecting disease progression. UNC13B, which is closely related to UNC13A, plays a role in autism spectrum disorders (ASD), epilepsy, and schizophrenia. UNC13C is implicated in oral squamous cell carcinoma (OSCC) and hepatocellular carcinoma (HCC), and has a neuroprotective role in Alzheimer's disease (AD). UNC13D has an essential role in immune cell function, making it a key player in FHL. This review highlights the distinct molecular functions of each UNC13 family member and their implications in disease contexts, shedding light on potential therapeutic strategies and avenues for future research. Understanding these proteins' roles offers new insights into the management and treatment of neurological and immunological disorders.}, } @article {pmid38188002, year = {2023}, author = {Ansari, U and Wen, J and Taguinod, I and Nadora, D and Nadora, D and Lui, F}, title = {Exploring dietary approaches in the prevention and management of Amyotrophic Lateral Sclerosis: A literature review.}, journal = {AIMS neuroscience}, volume = {10}, number = {4}, pages = {376-387}, pmid = {38188002}, issn = {2373-7972}, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal and complex neurodegenerative disease of upper and lower motor neurons of the central nervous system. The pathogenesis of this multifaceted disease is unknown. However, diet has emerged as a modifiable risk factor that has neuroprotective effects towards other neurological disorders such as Alzheimer's, Parkinson's and dementia. Thus, this review aims to explore how diet can potentially influence ALS onset and/or progression. In this review, five popular diets (Mediterranean, Vegan, Carnivore, Paleolithic and Ketogenic) and their distinct macromolecule composition, nutritional profile, biochemical pathways and their potential therapeutic effects for ALS are thoroughly examined. However, the composition of these diets varies, and the data is controversial, with conflicting studies on the effectiveness of nutrient intake of several of these diets. Although these five diets show that a higher intake of foods containing anti-inflammatory and antioxidant compounds have a positive correlation towards reducing the oxidative stress of ALS, further research is needed to directly compare the effects of these diets and the mechanisms leading to ALS and its progression.}, } @article {pmid38187588, year = {2024}, author = {McKeever, PM and Sababi, AM and Sharma, R and Xu, Z and Xiao, S and McGoldrick, P and Ketela, T and Sato, C and Moreno, D and Visanji, N and Kovacs, GG and Keith, J and Zinman, L and Rogaeva, E and Goodarzi, H and Bader, GD and Robertson, J}, title = {Single-nucleus transcriptome atlas of orbitofrontal cortex in amyotrophic lateral sclerosis with a deep learning-based decoding of alternative polyadenylation mechanisms.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2023.12.22.573083}, pmid = {38187588}, issn = {2692-8205}, abstract = {Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) are two age-related and fatal neurodegenerative disorders that lie on a shared disease spectrum. While both disorders involve complex interactions between neuronal and glial cells, the specific cell-type alterations and their contributions to disease pathophysiology remain incompletely understood. Here, we applied single-nucleus RNA sequencing of the orbitofrontal cortex, a region affected in ALS-FTLD, to map cell-type specific transcriptional signatures in C9orf72-related ALS (with and without FTLD) and sporadic ALS cases. Our findings reveal disease- and cell-type-specific transcriptional changes, with neurons exhibiting the most pronounced alterations, primarily affecting mitochondrial function, protein homeostasis, and chromatin remodeling. A comparison with independent datasets from different cortical regions of C9orf72 and sporadic ALS cases showed concordance in several pathways, with neuronal STMN2 and NEFL showing consistent up-regulation between brain regions and disease subtypes. We also interrogated alternative polyadenylation (APA) as an additional layer of transcriptional regulation, demonstrating that APA events are not correlated with identified gene expression changes. To interpret these events, we developed APA-Net, a deep learning model that integrates transcript sequences with RNA-binding protein expression profiles, revealing cell type-specific patterns of APA regulation. Our atlas illuminates cell type-specific pathomechanisms of ALS/FTLD, providing a valuable resource for further investigation.}, } @article {pmid38187158, year = {2023}, author = {Yang, J and Liu, T and Zhang, L and Li, X and Du, FP and Liu, Q and Dong, H and Liu, Y}, title = {Eosinophils at diagnosis are elevated in amyotrophic lateral sclerosis.}, journal = {Frontiers in neurology}, volume = {14}, number = {}, pages = {1289467}, pmid = {38187158}, issn = {1664-2295}, abstract = {INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a rare, devastating neurodegenerative disease that affects upper and lower motor neurons. To date, no effective treatment or reliable biomarker for ALS has been developed. In recent years, many factors have been proposed as possible biomarkers of ALS; however, no consensus has been reached. Therefore, a reliable biomarker is urgently needed. Eosinophils may play a crucial role in healthy humans and diseases, and serve as a biomarker for many chronic diseases.

METHODS: Routine blood test results were collected from 66 healthy controls and 59 patients with ALS. The percentages and total numbers of each cell population were analyzed, and the correlation between these indicators and patient ALS functional rating scale-revised (ALSFRS-R) score or disease progression rate (ΔFS score) was analyzed.

RESULTS: Compared to healthy controls, the number of blood leukocytes, neutrophils, monocytes, and basophils was significantly decreased in patients with ALS (p = 0.002, p = 0.001, p = 0.049, and p < 0.0001, respectively). There was an increase in the number of eosinophils (p < 0.0001), but no difference in the number of lymphocytes between patients with ALS and healthy controls was found (p = 0.563). Compared to healthy controls, the percentage of neutrophils was decreased and the percentage of lymphocytes and eosinophils was increased in patients with ALS (p = 0.01, p = 0.012, and p = 0.001, respectively). There was no difference between patients with ALS and healthy controls in the percentage of monocytes and basophils (p = 0.622 and p = 0.09, respectively). However, only the percentage and number of eosinophils had a correlation with the ΔFS score. Further multivariate analysis revealed a significant correlation between the disease duration, eosinophil count and percentage, and the disease progression rate (p < 0.0001, p = 0.048, and p = 0.023, respectively). The neutrophil-to-eosinophil ratio (NER), lymphocyte-to-eosinophil ratio (LER), and monocyte-to-eosinophil ratio (MER) were significantly lower in patients with ALS than in healthy controls. However, only the LER was significantly correlated with the ΔFS score.

CONCLUSION: These observations implicate neutrophils, lymphocytes, and eosinophils as important factors, and increasing eosinophil counts were negatively correlated with the ΔFS score in patients with ALS.}, } @article {pmid38187117, year = {2023}, author = {Dorça, A and Vergara, J and Skoretz, SA and Brenner, MJ and Diniz, DS and Zeredo, JL and Sarmet, M}, title = {Respiratory support effect on pharyngeal area in patients with amyotrophic lateral sclerosis: A fluoroscopic comparison of NIV, helmet/CPAP, and high-flow nasal cannula.}, journal = {Respiratory medicine case reports}, volume = {46}, number = {}, pages = {101958}, pmid = {38187117}, issn = {2213-0071}, abstract = {The global use of noninvasive respiratory support provided by different supportive ventilation delivery methods (SVDMs) has increased, but the impact of these devices on the upper airway structures of patients with amyotrophic lateral sclerosis (ALS) is not known. We aimed to compare the pharyngeal cross-sectional area during spontaneous breathing with four different SVDMs: intranasal masks, oronasal masks, high-flow nasal cannula (HFNC), and helmet in patients with ALS. We compared measures of the pharyngeal area during spontaneous breathing and SVDM use. The greatest increase was observed with intranasal mask use, followed by HFNC, oronasal mask, and helmet respectively. In conclusion, upper airway opening in patients with ALS is enhanced by positive pressure with intranasal masks and HFNC, showing promise for increasing pharyngeal patency. Future studies should explore its applicability and effectiveness in maintaining long-term pharyngeal patency, especially in this population with bulbar weakness.}, } @article {pmid38185999, year = {2024}, author = {Liu, Z and Qiang, Y and Shan, S and Wang, S and Song, F}, title = {Carbon disulfide induces accumulation of TDP-43 in the cytoplasm and mitochondrial dysfunction in rat spinal cords.}, journal = {Cerebral cortex (New York, N.Y. : 1991)}, volume = {34}, number = {2}, pages = {}, doi = {10.1093/cercor/bhad526}, pmid = {38185999}, issn = {1460-2199}, support = {82173552//National Natural Science Foundation of China/ ; }, mesh = {Humans ; Rats ; Animals ; *Carbon Disulfide/metabolism ; *Neuroblastoma/metabolism/pathology ; Cytoplasm/metabolism ; DNA-Binding Proteins/metabolism ; *Amyotrophic Lateral Sclerosis/chemically induced/pathology ; Spinal Cord/pathology ; *Neurodegenerative Diseases/metabolism ; *Mitochondrial Diseases/metabolism/pathology ; }, abstract = {The relationship between environmental neurotoxicant exposure and neurodegenerative diseases is being extensively investigated. Carbon disulfide, a classic neurotoxicant and prototype of dithiocarbamates fungicides and anti-inflammatory agents, has been detected in urban adults, raising questions about whether exposure to carbon disulfide is associated with a high incidence of neurodegenerative diseases. Here, using rat models and SH-SY5Y cells, we investigated the possible mechanistic linkages between carbon disulfide neurotoxicity and the expression of TDP-43 protein, a marker of amyotrophic lateral sclerosis/frontotemporal lobar degeneration. Our results showed that rats exhibited severe dyskinesia and increased TDP-43 expression in the spinal cord following carbon disulfide exposure. Moreover, carbon disulfide exposure induced abnormal cytoplasmic localization and phosphorylation of TDP-43 in motor neurons. Importantly, carbon disulfide treatment led to the accumulation of TDP-43 in the mitochondria of motor neurons and resulted in subsequent mitochondrial damage, including mitochondrial structural disruption, mitochondrial respiratory chain complex I inhibition, and impaired VCP/p97-dependent mitophagy. In summary, our study provides support for carbon disulfide exposure-mediated TDP-43 mislocalization and mitochondrial dysfunction, contributes to understanding the pathogenesis of environmental neurotoxin-induced neurodegeneration, and provides inspiration for potential therapeutic strategies.}, } @article {pmid38185916, year = {2024}, author = {Barber, S and Gomez-Godinez, V and Young, J and Wei, A and Chen, S and Snissarenko, A and Chan, SS and Wu, C and Shi, L}, title = {Impacts of H2O2, SARM1 inhibition, and high NAm concentrations on Huntington's disease laser-induced degeneration.}, journal = {Journal of biophotonics}, volume = {17}, number = {3}, pages = {e202300370}, doi = {10.1002/jbio.202300370}, pmid = {38185916}, issn = {1864-0648}, support = {//Beckman Laser Inc/ ; }, mesh = {Animals ; Mice ; Humans ; *Hydrogen Peroxide ; Niacinamide ; *Huntington Disease ; Mice, Knockout ; Neurons/metabolism ; Cytoskeletal Proteins/metabolism ; Armadillo Domain Proteins/genetics/metabolism ; }, abstract = {Axonal degeneration is a key component of neurodegenerative diseases such as Huntington's disease (HD), Alzheimer's disease, and amyotrophic lateral sclerosis. Nicotinamide, an NAD+ precursor, has long since been implicated in axonal protection and reduction of degeneration. However, studies on nicotinamide (NAm) supplementation in humans indicate that NAm has no protective effect. Sterile alpha and toll/interleukin receptor motif-containing protein 1 (SARM1) regulates several cell responses to axonal damage and has been implicated in promoting neuronal degeneration. SARM1 inhibition seems to result in protection from neuronal degeneration while hydrogen peroxide has been implicated in oxidative stress and axonal degeneration. The effects of laser-induced axonal damage in wild-type and HD dorsal root ganglion cells treated with NAm, hydrogen peroxide (H2O2), and SARM1 inhibitor DSRM-3716 were investigated and the cell body width, axon width, axonal strength, and axon shrinkage post laser-induced injury were measured.}, } @article {pmid38185101, year = {2024}, author = {Huber, T and Krüerke, D and Simões-Wüst, AP}, title = {How Physicians and Nursing Staff Perceive Effectiveness and Tolerability of Bryophyllum Preparations: An Online Survey in an Anthroposophic Hospital.}, journal = {Complementary medicine research}, volume = {31}, number = {2}, pages = {116-123}, pmid = {38185101}, issn = {2504-2106}, mesh = {Humans ; Male ; Surveys and Questionnaires ; Female ; Adult ; Switzerland ; *Kalanchoe ; Anthroposophy ; Middle Aged ; *Attitude of Health Personnel ; *Nursing Staff, Hospital/psychology/statistics & numerical data ; *Physicians/psychology ; *Phytotherapy ; *Plant Extracts/therapeutic use ; *Medical Staff, Hospital/psychology ; }, abstract = {BACKGROUND: Bryophyllum preparations are widely used in anthroposophic medicine, most often for mental and behavioural disorders. Three prospective studies have revealed positive effects of Bryophyllum pinnatum on sleep quality, and various trials have shown very good tolerability. Results from animal models have indicated CNS depressant and anxiolytic effects. This survey was conducted at the hospital "Klinik Arlesheim" in Switzerland to find out how the physicians and the nursing staff perceive the effectiveness and the tolerability of the Bryophyllum preparations they most frequently use.

DESIGN: Internal, anonymous online survey of healthcare professionals (April 8-May 31, 2022). The questionnaire comprised 105 multiple-choice questions. Answering the questions was taken as consent to participate in the survey.

PARTICIPANTS AND METHODS: All physicians and nursing staff with a valid email address at the hospital "Klinik Arlesheim AG" were invited via email to participate in this REDCap survey. The data were analysed descriptively.

RESULTS: Out of 266 invited participants, 48 answered some and 36 answered all questions (response rate between 18.0% and 13.5%). The participants had long experience with Bryophyllum preparations and were comprised approximately equal numbers of physicians and nursing staff. Various Bryophyllum preparations from the hospital's own production and Wala Heilmittel GmbH (in both cases produced from the species B. daigremontianum) and from Weleda AG (species B. pinnatum) were used. The indications for which most participants had prescribed or administered Bryophyllum preparations "very frequently" were anxiety, sleep disorders, crisis situations in oncology, posttraumatic stress disorder, benzodiazepine dependence/withdrawal, and depression. Improvements such as relief from restlessness, decreased anxiety, balance, easier falling asleep, better sleeping through, increased resilience, mood elevation, and less urge to move one's legs were reported "frequently" or "very frequently." Almost all participants agreed that Bryophyllum can be used to reduce the intake of synthetic sedatives or psychotropic drugs, but only approximately half believed that it could replace them. The majority of participants mentioned good tolerability of the various products, but a few reported occasional stomach or intestinal irritation, daytime fatigue, drowsiness, diarrhoea, and nausea.

CONCLUSION: Bryophyllum preparations are perceived as helpful in the treatment of various mental disorders, particularly anxiety, and are generally well tolerated. Most of these preparations are used for indications that have not yet been clinically investigated.

UNLABELLED: HintergrundBryophyllum-Präparate werden in der Anthroposophischen Medizin sehr häufig zur Behandlung von psychischen und Verhaltensstörungen eingesetzt. Drei prospektive Studien zeigten zudem positive Wirkungen von Bryophyllum pinnatum (BP) auf die Schlafqualität. Auch die Verträglichkeit wurde in allen bisherigen Studien als sehr gut bewertet. In Tiermodellen wurden ZNS-depressive und anxiolytische Effekte von BP festgestellt. Die hier durchgeführte Umfrage fand an der Klinik Arlesheim (Schweiz) statt. Sie diente dazu herauszufinden, wie Ärztinnen und Ärzte sowie das Pflegepersonal die Wirksamkeit und Verträglichkeit der von ihnen am häufigsten verwendeten Bryophyllum-Präparate wahrnehmen.DesignInterne, anonyme, Online-Befragung unter ärztlichen und pflegerischen Fachkräften (8. April–31. Mai 2022). Der Fragebogen umfasste 105 Multiple-Choice-Fragen. Die Beantwortung der Fragen wurde als Zustimmung zur Teilnahme an der Umfrage interpretiert.Teilnehmende und MethodenAlle Ärztinnen, Ärzte und Pflegefachpersonen mit einer gültigen E-Mail-Adresse der “Klinik Arlesheim AG” wurden per E-Mail eingeladen, an dieser REDCap-Umfrage teilzunehmen. Die Daten wurden deskriptiv ausgewertet.ErgebnisseVon den 266 eingeladenen Teilnehmenden beantworteten 48 einige und 36 alle Fragen (Antwortquote zwischen 18.0% und 13.5%). Die Teilnehmenden hatten langjährige Erfahrung mit Bryophyllum-Präparaten und setzten sich etwa zu gleichen Teilen aus ärztlichen und pflegerischen Fachkräften zusammen. Die Resultate zeigen, dass verschiedenste Bryophyllum-Präparate aus klinikeigener Herstellung, von der Wala Heilmittel GmbH (Art B. daigremontianum) und von der Weleda AG (Art B. pinnatum) verwendet werden. Zu den Indikationen, bei denen die meisten Teilnehmenden Bryophyllum-Präparate “sehr häufig” verordnet oder angewendet haben, gehören Angstzustände, Schlafstörungen, Krisensituationen in der Onkologie, Posttraumatische Belastungsstörung, Benzodiazepin-Abhängigkeit/Entzug und Depressionen. Gesundheitsverbesserungen wie Linderung von Unruhe, verminderte Angst, Ausgeglichenheit, leichteres Einschlafen, besseres Durchschlafen, erhöhte Belastbarkeit, Stimmungsaufhellung und weniger Drang, die Beine zu bewegen, wurden als “häufig” oder “sehr häufig” angegeben. Fast alle Teilnehmenden waren sich einig, dass Bryophyllum verwendet werden kann, um die Einnahme von synthetischen Beruhigungsmitteln oder Psychopharmaka zu reduzieren, aber nur etwa die Hälfte gab an, dass es diese ersetzen kann. Die Mehrheit der Teilnehmenden spricht von einer guten Verträglichkeit der verschiedenen Produkte. Einige wenige berichteten von gelegentlicher Magen- oder Darmreizung, Tagesmüdigkeit, Schläfrigkeit, Durchfall und Übelkeit.SchlussfolgerungBryophyllum-Präparate werden als hilfreich bei der Behandlung verschiedener psychischen Störungen, insbesondere bei Angstzuständen, angesehen und im Allgemeinen gut vertragen. Die meisten der angegebenen Präparate werden für Indikationen verwendet, die noch nicht klinisch untersucht worden sind.}, } @article {pmid38184629, year = {2024}, author = {Klíčová, K and Mareš, J and Menšíková, K and Kaiserová, M and Friedecký, D and Kaňovský, P and Strnad, M and Matěj, R}, title = {Utilizing neurodegenerative markers for the diagnostic evaluation of amyotrophic lateral sclerosis.}, journal = {European journal of medical research}, volume = {29}, number = {1}, pages = {31}, pmid = {38184629}, issn = {2047-783X}, support = {CZ.02.1.01 / 0.0 / 0.0 / 16_019 / 0000868//European Regional Development Fund - ENOCH project/ ; NV19-04-00090//Grant Agency of the Ministry of Health/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis ; Clusterin ; Delayed Diagnosis ; tau Proteins ; Biomarkers ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by progressive deterioration of upper and lower motor neurons. A definitive diagnostic test or biomarker for ALS is currently unavailable, leading to a diagnostic delay following the onset of initial symptoms. Our study focused on cerebrospinal fluid (CSF) concentrations of clusterin, tau protein, phosphorylated tau protein, and beta-amyloid1-42 in ALS patients and a control group.

METHODS: Our study involved 54 ALS patients and 58 control subjects. Among the ALS patients, 14 presented with bulbar-onset ALS, and 40 with limb-onset ALS. We quantified biomarker levels using enzyme-linked immunosorbent assay (ELISA) and compared the results using the Mann-Whitney U-test.

RESULTS: Significant elevations in neurodegenerative markers, including tau protein (p < 0.0001), phosphorylated tau protein (p < 0.0001), and clusterin (p = 0.038), were observed in ALS patients compared to controls. Elevated levels of tau protein and phosphorylated tau protein were also noted in both bulbar and limb-onset ALS patients. However, no significant difference was observed for beta-amyloid1-42. ROC analysis identified tau protein (AUC = 0.767) and p-tau protein (AUC = 0.719) as statistically significant predictors for ALS.

CONCLUSION: Our study demonstrates that neurodegenerative marker levels indicate an ongoing neurodegenerative process in ALS. Nonetheless, the progression of ALS cannot be predicted solely based on these markers. The discovery of a specific biomarker could potentially complement existing diagnostic criteria for ALS.}, } @article {pmid38183652, year = {2024}, author = {Guise, AJ and Misal, SA and Carson, R and Chu, JH and Boekweg, H and Van Der Watt, D and Welsh, NC and Truong, T and Liang, Y and Xu, S and Benedetto, G and Gagnon, J and Payne, SH and Plowey, ED and Kelly, RT}, title = {TDP-43-stratified single-cell proteomics of postmortem human spinal motor neurons reveals protein dynamics in amyotrophic lateral sclerosis.}, journal = {Cell reports}, volume = {43}, number = {1}, pages = {113636}, pmid = {38183652}, issn = {2211-1247}, support = {R01 GM138931/GM/NIGMS NIH HHS/United States ; R33 CA225248/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics ; DNA-Binding Proteins/metabolism ; Motor Neurons/metabolism ; Proteome/metabolism ; Proteomics ; }, abstract = {A limitation of conventional bulk-tissue proteome studies in amyotrophic lateral sclerosis (ALS) is the confounding of motor neuron (MN) signals by admixed non-MN proteins. Here, we leverage laser capture microdissection and nanoPOTS single-cell mass spectrometry-based proteomics to query changes in protein expression in single MNs from postmortem ALS and control tissues. In a follow-up analysis, we examine the impact of stratification of MNs based on cytoplasmic transactive response DNA-binding protein 43 (TDP-43)+ inclusion pathology on the profiles of 2,238 proteins. We report extensive overlap in differentially abundant proteins identified in ALS MNs with or without overt TDP-43 pathology, suggesting early and sustained dysregulation of cellular respiration, mRNA splicing, translation, and vesicular transport in ALS. Together, these data provide insights into proteome-level changes associated with TDP-43 proteinopathy and begin to demonstrate the utility of pathology-stratified trace sample proteomics for understanding single-cell protein dynamics in human neurologic diseases.}, } @article {pmid38183365, year = {2024}, author = {Barć, K and Finsel, J and Helczyk, O and Baader, S and Aho-Özhan, H and Ludolph, AC and Lulé, D and Kuźma-Kozakiewicz, M}, title = {One third of physicians discuss exit strategies with patients with amyotrophic lateral sclerosis: Results from nationwide surveys among German and Polish neurologists.}, journal = {Brain and behavior}, volume = {14}, number = {2}, pages = {e3243}, pmid = {38183365}, issn = {2162-3279}, support = {NEEDSinALS 01ED1405//EU Joint Programme-Neurodegenerative Disease Research/ ; FTLDc O1GI1007A//Bundesministerium für Bildung und Forschung/ ; MND-Net 01GM1103A//Bundesministerium für Bildung und Forschung/ ; PaCeMed 01DS18031//Bundesministerium für Bildung und Forschung/ ; K.N.K.B.008.04//Kompetenznetzwerk Präventivmedizin Baden-Württemberg/ ; //Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE)/ ; }, abstract = {OBJECTIVE: This paper examines neurologists' approaches to exit strategies (ESs), such as euthanasia and physician-assisted suicide, in patients with amyotrophic lateral sclerosis (PALS) in two European countries.

METHODS: In a nationwide anonymous survey, we collected responses from 237 Polish and 228 German neurologists, focusing on their practices and beliefs about ESs, as well as their viewpoints on life-sustaining measures (LSMs) (percutaneous endoscopic gastrostomy, non-invasive, and invasive ventilation). To analyze the data, we employed statistical methods, including Mann-Whitney U, Kruskal-Wallis, chi-square tests, Spearman's rank correlation, and multiple regression analysis.

RESULTS: One third of the neurologists initiated the discussion about ESs with PALS. Half were ready to have this conversation upon patient's request. Age, gender, religiousness, and nationality were closely associated with this approach. One in 9 neurologists received a request to terminate an LSM, whereas 1 in 10 to implement an ES. German neurologists and palliative care trainees acquired both demands more commonly. Neurologists quoted a low quality of life, decreased mood, and being a burden to the family/closest ones as primary reasons for a wish to hasten death among PALS. Although the majority expressed a willingness to terminate an LSM at a request of the patient, most opposed the legalization of euthanasia. Younger and less religious individuals were more likely to favor accepting euthanasia.

CONCLUSION: Neurologists vary significantly in their approaches to terminal care. Complex relationships exist among personal indices, shared beliefs, and current practices.}, } @article {pmid38182485, year = {2024}, author = {Mainous, RO and Dunlap, JJ and Brewer, TL}, title = {Author Response to Kesten et al's Letter to the Editor.}, journal = {Nursing outlook}, volume = {72}, number = {2}, pages = {102106}, doi = {10.1016/j.outlook.2023.102106}, pmid = {38182485}, issn = {1528-3968}, } @article {pmid38182429, year = {2024}, author = {Lee, YJ and Rio, DC}, title = {A mutation in the low-complexity domain of splicing factor hnRNPA1 linked to amyotrophic lateral sclerosis disrupts distinct neuronal RNA splicing networks.}, journal = {Genes & development}, volume = {38}, number = {1-2}, pages = {11-30}, pmid = {38182429}, issn = {1549-5477}, support = {S10 RR026866/RR/NCRR NIH HHS/United States ; R35 GM118121/GM/NIGMS NIH HHS/United States ; S10 RR029668/RR/NCRR NIH HHS/United States ; S10 RR025622/RR/NCRR NIH HHS/United States ; R01 GM097352/GM/NIGMS NIH HHS/United States ; S10 RR027303/RR/NCRR NIH HHS/United States ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/metabolism ; *Heterogeneous-Nuclear Ribonucleoprotein Group A-B/genetics/metabolism ; Mutation ; *Neurodegenerative Diseases ; RNA Splicing/genetics ; RNA Splicing Factors/genetics ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a debilitating neurodegenerative disease characterized by loss of motor neurons. Human genetic studies have linked mutations in RNA-binding proteins as causative for this disease. The hnRNPA1 protein, a known pre-mRNA splicing factor, is mutated in some ALS patients. Here, two human cell models were generated to investigate how a mutation in the C-terminal low-complexity domain (LCD) of hnRNPA1 can cause splicing changes of thousands of transcripts that collectively are linked to the DNA damage response, cilium organization, and translation. We show that the hnRNPA1 D262V mutant protein binds to new binding sites on differentially spliced transcripts from genes that are linked to ALS. We demonstrate that this ALS-linked hnRNPA1 mutation alters normal RNA-dependent protein-protein interactions. Furthermore, cells expressing this hnRNPA1 mutant exhibit a cell aggregation phenotype, markedly reduced growth rates, changes in stress granule kinetics, and aberrant growth of neuronal processes. This study provides insight into how a single amino acid mutation in a splicing factor can alter RNA splicing networks of genes linked to ALS.}, } @article {pmid38181637, year = {2024}, author = {Wen, S and Fu, S and Gao, C and Lei, K and Liu, X}, title = {Generation of two induced pluripotent stem cell lines from two sporadic amyotrophic lateral sclerosis patients.}, journal = {Stem cell research}, volume = {74}, number = {}, pages = {103288}, doi = {10.1016/j.scr.2023.103288}, pmid = {38181637}, issn = {1876-7753}, mesh = {Male ; Female ; Humans ; Middle Aged ; *Induced Pluripotent Stem Cells/metabolism ; *Amyotrophic Lateral Sclerosis/pathology ; Leukocytes, Mononuclear/metabolism ; Kruppel-Like Factor 4 ; Cell Differentiation ; }, abstract = {Peripheral blood mononuclear cells were obtained from two patients diagnosed with amyotrophic lateral sclerosis (ALS), a 47-year-old female and a 45-year-old male. Induced pluripotent stem cells (iPSCs) were generated using a non-integrating SeV-based method, delivering the transcription factors OCT4, SOX2, c-MYC, and KLF4. These transgene-free iPSC lines exhibited typical pluripotent cell morphology, expressed pluripotency-associated markers, and had tri-lineage differentiation potential. Both iPSC lines were free of mycoplasma contamination and displayed normal karyotypes. The availability of these two cell lines provides a promising opportunity to use sporadic ALS models for investigating the intricate pathological mechanisms of ALS.}, } @article {pmid38180612, year = {2024}, author = {Lin, CY and Wu, HE and Weng, EF and Wu, HC and Su, TP and Wang, SM}, title = {Fluvoxamine Exerts Sigma-1R to Rescue Autophagy via Pom121-Mediated Nucleocytoplasmic Transport of TFEB.}, journal = {Molecular neurobiology}, volume = {61}, number = {8}, pages = {5282-5294}, pmid = {38180612}, issn = {1559-1182}, mesh = {*Sigma-1 Receptor ; *Fluvoxamine/pharmacology ; *Receptors, sigma/metabolism ; *Autophagy/drug effects ; *Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/metabolism ; Humans ; *Active Transport, Cell Nucleus/drug effects ; Animals ; Mice ; Cell Nucleus/metabolism/drug effects ; C9orf72 Protein/metabolism/genetics ; Cell Line ; }, abstract = {Expansion of the GGGGCC-RNA repeat is a known cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), which currently have no cure. Recent studies have indicated the activation of Sigma-1 receptor plays an important role in providing neuroprotection, especially in ALS and Alzheimer's disease. Nevertheless, the mechanisms underlying Sigma-1R activation and its effect on (G4C2)n-RNA-induced cell death remain unclear. In this study, we demonstrated that fluvoxamine is a Sigma-1R agonist that can increase chaperone activity and stabilize the protein expression of Pom121 in (G4C2)31-RNA-expressing NSC34 cells, leading to increased colocalization at the nuclear envelope. Interestingly, fluvoxamine treatment increased Pom121 protein expression without affecting transcription. In C9orf72-ALS, the nuclear translocation of TFEB autophagy factor decreased owing to nucleocytoplasmic transport defects. Our results showed that pretreatment of NSC34 cells with fluvoxamine promoted the shuttling of TFEB into the nucleus and elevated the expression of LC3-II compared to the overexpression of (G4C2)31-RNA alone. Additionally, even when used alone, fluvoxamine increases Pom121 expression and TFEB translocation. To summarize, fluvoxamine may act as a promising repurposed medicine for patients with C9orf72-ALS, as it stabilizes the nucleoporin Pom121 and promotes the translocation of TFEB in (G4C2)31-RNA-expressing NSC34 cells.}, } @article {pmid38180358, year = {2024}, author = {Ferguson, R and van Es, MA and van den Berg, LH and Subramanian, V}, title = {Neural stem cell homeostasis is affected in cortical organoids carrying a mutation in Angiogenin.}, journal = {The Journal of pathology}, volume = {262}, number = {4}, pages = {410-426}, doi = {10.1002/path.6244}, pmid = {38180358}, issn = {1096-9896}, support = {084562/Z/07/Z/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics ; *Frontotemporal Dementia/genetics/pathology ; *Neural Stem Cells/metabolism ; Mutation ; Homeostasis ; *Ribonuclease, Pancreatic ; }, abstract = {Mutations in Angiogenin (ANG) and TARDBP encoding the 43 kDa transactive response DNA binding protein (TDP-43) are associated with amyotrophic lateral sclerosis and frontotemporal dementia (ALS-FTD). ANG is neuroprotective and plays a role in stem cell dynamics in the haematopoietic system. We obtained skin fibroblasts from members of an ALS-FTD family, one with mutation in ANG, one with mutation in both TARDBP and ANG, and one with neither mutation. We reprogrammed these fibroblasts to induced pluripotent stem cells (iPSCs) and generated cortical organoids as well as induced stage-wise differentiation of the iPSCs to neurons. Using these two approaches we investigated the effects of FTD-associated mutations in ANG and TARDBP on neural precursor cells, neural differentiation, and response to stress. We observed striking neurodevelopmental defects such as abnormal and persistent rosettes in the organoids accompanied by increased self-renewal of neural precursor cells. There was also a propensity for differentiation to later-born neurons. In addition, cortical neurons showed increased susceptibility to stress, which is exacerbated in neurons carrying mutations in both ANG and TARDBP. The cortical organoids and neurons generated from patient-derived iPSCs carrying ANG and TARDBP gene variants recapitulate dysfunctions characteristic of frontotemporal lobar degeneration observed in FTD patients. These dysfunctions were ameliorated upon treatment with wild type ANG. In addition to its well-established role during the stress response of mature neurons, ANG also appears to play a role in neural progenitor dynamics. This has implications for neurogenesis and may indicate that subtle developmental defects play a role in disease susceptibility or onset. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.}, } @article {pmid38179776, year = {2023}, author = {Yang, EJ and Lee, SH}, title = {Anti-Inflammatory Effects of Chaenomeles sinensis Extract in an ALS Animal Model.}, journal = {Frontiers in bioscience (Landmark edition)}, volume = {28}, number = {12}, pages = {326}, doi = {10.31083/j.fbl2812326}, pmid = {38179776}, issn = {2768-6698}, support = {NRF-2020R1A2C2006703//National Research Foundation of Korea, South Korea/ ; KSN2212010//KIOM, South Korea/ ; C18040//KIOM, South Korea/ ; }, mesh = {Humans ; Mice ; Animals ; *Amyotrophic Lateral Sclerosis/drug therapy/genetics/pathology ; Mice, Transgenic ; Disease Models, Animal ; Spinal Cord ; *Rosaceae/chemistry ; Antioxidants/pharmacology/therapeutic use ; Plant Extracts/pharmacology/therapeutic use ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a systemic disease with multiple pathological effects, including neuroinflammation, oxidative stress, autophagy, mitochondrial dysfunction, and endoplasmic reticulum stress. Despite many studies seeking to identify and develop effective therapies, effective ALS treatment has yet to be approved. Hence, patients with ALS ultimately experience muscle atrophy and loss of motor neurons. Herbal medicines have been used to treat numerous diseases by modulating multiple biological processes and exerting pharmacological effects, including anti-inflammatory and antioxidant properties. In particular, Chaenomeles sinensis Koehne (CS) exhibits anti-hyperuricemic and nephroprotective effects and is used to treat anaphylaxis, viral infections, and neurodegenerative diseases, such as Alzheimer's disease. This study monitored the effects of CS supplementation on muscle function and motor neurons in hSOD1G93A mice, an established ALS animal model.

METHODS: Body weight measurements and behavioral tests were performed; additionally, western blotting and immunohistochemistry analyses were conducted using the mice gastrocnemius, tibialis anterior, and spinal cord.

RESULTS: CS augmented anti-inflammatory and antioxidant effects in the muscle and spinal cord of hSOD1G93A mice. Furthermore, CS improved motor function and regulated autophagy in the muscles of the hSOD1G93A mice.

CONCLUSIONS: CS might represent a promising supplement for improving motor function and delaying ALS progression. However, its development for clinical use warrants further investigation.}, } @article {pmid38179454, year = {2023}, author = {Li, H and Liu, S and Zhang, K and Zhu, X and Dai, J and Lu, Y}, title = {Gut microbiome and plasma metabolome alterations in myopic mice.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1251243}, pmid = {38179454}, issn = {1664-302X}, abstract = {BACKGROUND: Myopia is one of the most common eye diseases leading to blurred distance vision. Inflammatory diseases could trigger or exacerbate myopic changes. Although gut microbiota bacteria are associated with various inflammatory diseases, little is known about its role in myopia.

MATERIALS AND METHODS: The mice were randomly divided into control and model groups, with the model group being attached-30D lens onto the eyes for 3 weeks. Then, mouse cecal contents and plasma were collected to analyze their intestinal microbiota and plasma metabolome.

RESULTS: We identified that the microbial composition differed considerably between the myopic and non-myopic mice, with the relative abundance of Firmicutes phylum decreased obviously while that of Actinobacteria phylum was increased in myopia. Furthermore, Actinobacteria and Bifidobacterium were positively correlated with axial lengths (ALs) of eyeballs while negatively correlated with refractive diopters. Untargeted metabolomic analysis identified 141 differentially expressed metabolites, and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis revealed considerable enrichment mainly in amino acid metabolism pathways. Notably, pathways involved glutamate metabolism including "Glutamine and D-glutamate metabolism" and "Alanine, aspartate and glutamate metabolism" was changed dramatically, which presented as the concentrations of L-Glutamate and L-Glutamine decreased obviously in myopia. Interestingly, microbiome dysbiosis and metabolites alternations in myopia have a disrupting gut barrier feature. We further demonstrated that the gut barrier function was impaired in myopic mice manifesting in decreased expression of Occludin, ZO-1 and increased permeation of FITC-dextran.

DISCUSSION: Myopic mice had obviously altered gut microbiome and metabolites profiles compared to non-myopic mice. The dysbiosis and plasma metabolomics shift in myopia had an interrupting gut barrier feature. Our study provides new insights into the possible role of the gut microbiota in myopia and reinforces the potential feasibility of microbiome-based therapies in myopia.}, } @article {pmid38179225, year = {2023}, author = {Ji, X and Walczak, P and Boltze, J}, title = {Exploring novel experimental treatments for major neurodegenerative disorders.}, journal = {Neuroprotection}, volume = {1}, number = {2}, pages = {81-83}, pmid = {38179225}, issn = {2770-730X}, support = {R01 DA056739/DA/NIDA NIH HHS/United States ; }, } @article {pmid38178841, year = {2023}, author = {Zhao, S and Chen, R and Gao, Y and Lu, Y and Bai, X and Zhang, J}, title = {Fundamental roles of the Optineurin gene in the molecular pathology of Amyotrophic Lateral Sclerosis.}, journal = {Frontiers in neuroscience}, volume = {17}, number = {}, pages = {1319706}, pmid = {38178841}, issn = {1662-4548}, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the progressive loss of motor neurons (MNs) in the brain and spinal cord. It is caused by multiple factors, including mutations in any one of several specific genes. Optineurin (OPTN) mutation is an essential cause of some familial and sporadic ALS. Besides, as a multifunctional protein, OPTN is highly expressed and conserved in the central nervous system. OPTN exerts its functions by interacting with various proteins, often acting as an adaptor to provide a link between two or more core proteins related to autophagy and inflammation, etc. OPTN mutation mainly results in its function deficiency, which alters these interactions, leading to functional impairment in many processes. Meanwhile, OPTN immunopositive inclusions are also confirmed in the cases of ALS due to C9ORF72, FUS, TARDBP, and SOD1 mutations. Therefore, OPTN gene may play fundamental roles in the molecular pathology of ALS in addition to OPTN mutation. In this review, we summarize the recent advances in the ALS pathology of OPTN defect, such as mitophagy disorder, neuroinflammation, neuronal axonal degeneration, vesicular transport dysfunction, etc., which will provide a reference for research on the pathogenesis and treatment of ALS.}, } @article {pmid38178788, year = {2024}, author = {Noda, I}, title = {Two-Dimensional Correlation Spectroscopy (2D-COS) Analysis of Evolving Hyperspectral Images.}, journal = {Applied spectroscopy}, volume = {}, number = {}, pages = {37028231222011}, doi = {10.1177/00037028231222011}, pmid = {38178788}, issn = {1943-3530}, abstract = {The evolutionary behavior is examined for heterogeneously distributed hyperspectral images of a simulated biological tissue sample comprising lipid-like and protein-like components during the aging process. Taking a simple planar average of a spectral image loses useful information about the spatially resolved nature of the data. In contrast, multivariate curve resolution (MCR) analysis of a spectral image at a given stage of aging produces a set of loadings of major component groups. Each loading represents the combined spectral contributions of a mixture of similar but not identical constituents (i.e., lipid-like and protein-like components). Temporal analysis of individual component groups using two-dimensional correlation spectroscopy (2D-COS) and MCR provides much-streamlined results without interferences from the overlapped contributions. Grouping of data into separate components also allows for the effective comparison of the parallel processes of lipid oxidation and protein denaturation involving a number of constituents using the heterocomponent 2D-COS analysis. The complex interplays of lipid constituents and protein secondary structures during the tissue aging process are unambiguously highlighted. The possibility of extending this approach to a much more general form of applications using a moving window analysis is also discussed.}, } @article {pmid38178578, year = {2024}, author = {Haider, R and Penumutchu, S and Boyko, S and Surewicz, WK}, title = {Phosphomimetic substitutions in TDP-43's transiently α-helical region suppress phase separation.}, journal = {Biophysical journal}, volume = {123}, number = {3}, pages = {361-373}, pmid = {38178578}, issn = {1542-0086}, support = {S10 OD024996/OD/NIH HHS/United States ; F30 AG071339/AG/NIA NIH HHS/United States ; T32 NS077888/NS/NINDS NIH HHS/United States ; RF1 AG061797/AG/NIA NIH HHS/United States ; T32 GM007250/GM/NIGMS NIH HHS/United States ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/metabolism ; DNA-Binding Proteins/metabolism ; *Frontotemporal Lobar Degeneration/metabolism ; Phase Separation ; Phosphorylation ; }, abstract = {Phosphorylated TAR DNA-binding protein of 43 kDa (TDP-43) is present within the aggregates of several age-related neurodegenerative disorders, such as amyotrophic lateral sclerosis, frontotemporal lobar degeneration, and Alzheimer's disease, to the point that the presence of phosphorylated TDP-43 is considered a hallmark of some of these diseases. The majority of known TDP-43 phosphorylation sites detected in amyotrophic lateral sclerosis and frontotemporal lobar degeneration patients is located in the low-complexity domain (LCD), the same domain that has been shown to be critical for TDP-43 liquid-liquid phase separation (LLPS). However, the effect of these LCD phosphorylation sites on TDP-43 LLPS has been largely unexplored, and any work that has been done has mainly focused on sites near the C-terminal end of the LCD. Here, we used a phosphomimetic approach to explore the impact of phosphorylation at residues S332 and S333, sites located within the transiently α-helical region of TDP-43 that have been observed to be phosphorylated in disease, on protein LLPS. Our turbidimetry and fluorescence microscopy data demonstrate that these phosphomimetic substitutions greatly suppress LLPS, and solution NMR data strongly suggest that this effect is at least in part due to the loss of α-helical propensity of the phosphomimetic protein variant. We also show that the S332D and S333D substitutions slow TDP-43 LCD droplet aging and fibrillation of the protein. Overall, these findings provide a biophysical basis for understanding the effect of phosphorylation within the transiently α-helical region of TDP-43 LCD on protein LLPS and fibrillation, suggesting that phosphorylation at residues 332 and 333 is not necessarily directly related to the pathogenic process.}, } @article {pmid38178278, year = {2024}, author = {Meira, MDV and Silva, RSD and Chochinov, HM and Medeiros, MOSF and Ferreira, MMM and de Góes Salvetti, M}, title = {Effects of Dignity Therapy on individuals with amyotrophic lateral sclerosis: Case studies.}, journal = {Palliative & supportive care}, volume = {22}, number = {3}, pages = {517-525}, doi = {10.1017/S1478951523001888}, pmid = {38178278}, issn = {1478-9523}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/psychology/complications/therapy ; Female ; Male ; Middle Aged ; Aged ; Qualitative Research ; Respect ; Personhood ; Surveys and Questionnaires ; Quality of Life/psychology ; Dignity Therapy ; }, abstract = {OBJECTIVES: To analyze the effects of Dignity Therapy (DT) on the physical, existential, and psychosocial symptoms of individuals with amyotrophic lateral sclerosis (ALS).

METHODS: This is a mixed-methods case study research that used the concurrent triangulation strategy to analyze the effects of DT on 3 individuals with ALS. Data collection included 3 instances of administering validated scales to assess multiple physical symptoms, anxiety, depression, spiritual well-being, and the Patient Dignity Inventory (PDI), followed by the implementation of DT and a semi-structured interview.

RESULTS: The scale results indicate that DT led to an improvement in the assessment of physical, social, emotional, spiritual, and existential symptoms according to the score results. It is worth noting that the patient with a recent diagnosis showed higher scores for anxiety and depression after DT. Regarding the PDI, the scores indicate improvements in the sense of dignity in all 3 cases, which aligns with the positive verbal reports after the implementation of DT.

SIGNIFICANCE OF RESULTS: This study allowed us to analyze the effects of DT on the physical, existential, and psychosocial symptoms of individuals with ALS, suggesting the potential benefits of this approach for this group of patients. Participants reported positive effects regarding pain and fatigue, could reflect on their life trajectories, and regained their value and meaning.}, } @article {pmid38178044, year = {2024}, author = {Peng, Q and Zhu, T and Huang, J and Liu, Y and Huang, J and Zhang, W}, title = {Factors and a model to predict three-month mortality in patients with acute fatty liver of pregnancy from two medical centers.}, journal = {BMC pregnancy and childbirth}, volume = {24}, number = {1}, pages = {27}, pmid = {38178044}, issn = {1471-2393}, support = {2023JJ40980//Natural Science Foundation of Hunan Province/ ; 2022JJ40789//Natural Science Foundation of Hunan Province/ ; 82301927//National Natural Science Foundation of China/ ; 82371700//National Natural Science Foundation of China/ ; }, mesh = {Female ; Humans ; Pregnancy ; *Fatty Liver/diagnosis/mortality ; Prognosis ; Retrospective Studies ; ROC Curve ; Severity of Illness Index ; *Pregnancy Complications/diagnosis/mortality ; Models, Biological ; }, abstract = {BACKGROUND: Acute fatty liver of pregnancy (AFLP) is an uncommon but potentially life-threatening complication. Lacking of prognostic factors and models renders prediction of outcomes difficult. This study aims to explore factors and develop a prognostic model to predict three-month mortality of AFLP.

METHODS: This retrospective study included 78 consecutive patients fulfilling both clinical and laboratory criteria and Swansea criteria for diagnosis of AFLP. Univariate and multivariate cox regression analyses were used to identify predictive factors of mortality. Predictive efficacy of prognostic index for AFLP (PI-AFLP) was compared with the other four liver disease models using receiver operating characteristic (ROC) curve.

RESULTS: AFLP-related three-month mortality of two medical centers was 14.10% (11/78). International normalised ratio (INR, hazard ratio [HR] = 3.446; 95% confidence interval [CI], 1.324-8.970), total bilirubin (TBIL, HR = 1.005; 95% CI, 1.000-1.010), creatine (Scr, HR = 1.007; 95% CI, 1.001-1.013), low platelet (PLT, HR = 0.964; 95% CI, 0.931-0.997) at 72 h postpartum were confirmed as significant predictors of mortality. Artificial liver support (ALS, HR = 0.123; 95% CI, 0.012-1.254) was confirmed as an effective measure to improve severe patients' prognosis. Predictive accuracy of PI-AFLP was 0.874. Area under the receiver operating characteristic curves (AUCs) of liver disease models for end-stage liver disease (MELD), MELD-Na, integrated MELD (iMELD) and pregnancy-specific liver disease (PSLD) were 0.781, 0.774, 0.744 and 0.643, respectively.

CONCLUSION: TBIL, INR, Scr and PLT at 72 h postpartum are significant predictors of three-month mortality in AFLP patients. ALS is an effective measure to improve severe patients' prognosis. PI-AFLP calculated by TBIL, INR, Scr, PLT and ALS was a sensitive and specific model to predict mortality of AFLP.}, } @article {pmid38177242, year = {2024}, author = {Shi, Y and Huang, L and Dong, H and Yang, M and Ding, W and Zhou, X and Lu, T and Liu, Z and Zhou, X and Wang, M and Zeng, B and Sun, Y and Zhong, S and Wang, B and Wang, W and Yin, C and Wang, X and Wu, Q}, title = {Decoding the spatiotemporal regulation of transcription factors during human spinal cord development.}, journal = {Cell research}, volume = {34}, number = {3}, pages = {193-213}, pmid = {38177242}, issn = {1748-7838}, support = {81891001//National Natural Science Foundation of China (National Science Foundation of China)/ ; 32122037//National Natural Science Foundation of China (National Science Foundation of China)/ ; }, mesh = {Animals ; Humans ; *Transcription Factors/genetics ; *Amyotrophic Lateral Sclerosis ; Neurogenesis ; Central Nervous System ; }, abstract = {The spinal cord is a crucial component of the central nervous system that facilitates sensory processing and motor performance. Despite its importance, the spatiotemporal codes underlying human spinal cord development have remained elusive. In this study, we have introduced an image-based single-cell transcription factor (TF) expression decoding spatial transcriptome method (TF-seqFISH) to investigate the spatial expression and regulation of TFs during human spinal cord development. By combining spatial transcriptomic data from TF-seqFISH and single-cell RNA-sequencing data, we uncovered the spatial distribution of neural progenitor cells characterized by combinatorial TFs along the dorsoventral axis, as well as the molecular and spatial features governing neuronal generation, migration, and differentiation along the mediolateral axis. Notably, we observed a sandwich-like organization of excitatory and inhibitory interneurons transiently appearing in the dorsal horns of the developing human spinal cord. In addition, we integrated data from 10× Visium to identify early and late waves of neurogenesis in the dorsal horn, revealing the formation of laminas in the dorsal horns. Our study also illuminated the spatial differences and molecular cues underlying motor neuron (MN) diversification, and the enrichment of Amyotrophic Lateral Sclerosis (ALS) risk genes in MNs and microglia. Interestingly, we detected disease-associated microglia (DAM)-like microglia groups in the developing human spinal cord, which are predicted to be vulnerable to ALS and engaged in the TYROBP causal network and response to unfolded proteins. These findings provide spatiotemporal transcriptomic resources on the developing human spinal cord and potential strategies for spinal cord injury repair and ALS treatment.}, } @article {pmid38177103, year = {2024}, author = {Bapat, O and Purimetla, T and Kruessel, S and Shah, M and Fan, R and Thum, C and Rupprecht, F and Langer, JD and Rangaraju, V}, title = {VAP spatially stabilizes dendritic mitochondria to locally support synaptic plasticity.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {205}, pmid = {38177103}, issn = {2041-1723}, mesh = {*Actins/metabolism ; *Dendritic Spines/metabolism ; Neuronal Plasticity ; Synapses/metabolism ; Mitochondria/metabolism ; }, abstract = {Synapses are pivotal sites of plasticity and memory formation. Consequently, synapses are energy consumption hotspots susceptible to dysfunction when their energy supplies are perturbed. Mitochondria are stabilized near synapses via the cytoskeleton and provide the local energy required for synaptic plasticity. However, the mechanisms that tether and stabilize mitochondria to support synaptic plasticity are unknown. We identified proteins exclusively tethering mitochondria to actin near postsynaptic spines. We find that VAP, the vesicle-associated membrane protein-associated protein implicated in amyotrophic lateral sclerosis, stabilizes mitochondria via actin near the spines. To test if the VAP-dependent stable mitochondrial compartments can locally support synaptic plasticity, we used two-photon glutamate uncaging for spine plasticity induction and investigated the induced and adjacent uninduced spines. We find VAP functions as a spatial stabilizer of mitochondrial compartments for up to ~60 min and as a spatial ruler determining the ~30 μm dendritic segment supported during synaptic plasticity.}, } @article {pmid38177100, year = {2024}, author = {Liu, ML and Ma, S and Tai, W and Zhong, X and Ni, H and Zou, Y and Wang, J and Zhang, CL}, title = {Screens in aging-relevant human ALS-motor neurons identify MAP4Ks as therapeutic targets for the disease.}, journal = {Cell death & disease}, volume = {15}, number = {1}, pages = {4}, pmid = {38177100}, issn = {2041-4889}, support = {R01 NS092616/NS/NINDS NIH HHS/United States ; R01 NS111776/NS/NINDS NIH HHS/United States ; R01 NS117065/NS/NINDS NIH HHS/United States ; R01 NS127375/NS/NINDS NIH HHS/United States ; }, mesh = {Mice ; Animals ; Adult ; Humans ; *Amyotrophic Lateral Sclerosis/drug therapy/genetics/metabolism ; *Neurodegenerative Diseases/metabolism ; Motor Neurons/metabolism ; Aging ; Disease Models, Animal ; Mice, Transgenic ; }, abstract = {Effective therapeutics is much needed for amyotrophic lateral sclerosis (ALS), an adult-onset neurodegenerative disease mainly affecting motor neurons. By screening chemical compounds in human patient-derived and aging-relevant motor neurons, we identify a neuroprotective compound and show that MAP4Ks may serve as therapeutic targets for treating ALS. The lead compound broadly improves survival and function of motor neurons directly converted from human ALS patients. Mechanistically, it works as an inhibitor of MAP4Ks, regulates the MAP4Ks-HDAC6-TUBA4A-RANGAP1 pathway, and normalizes subcellular distribution of RANGAP1 and TDP-43. Finally, in an ALS mouse model we show that inhibiting MAP4Ks preserves motor neurons and significantly extends animal lifespan.}, } @article {pmid38176936, year = {2023}, author = {Windhorst, U and Dibaj, P}, title = {Plastic Spinal Motor Circuits in Health and Disease.}, journal = {Journal of integrative neuroscience}, volume = {22}, number = {6}, pages = {167}, doi = {10.31083/j.jin2206167}, pmid = {38176936}, issn = {0219-6352}, mesh = {Animals ; Humans ; Spinal Cord ; *Amyotrophic Lateral Sclerosis ; *Muscular Atrophy, Spinal/pathology ; *Spinal Cord Injuries/pathology ; Disease Models, Animal ; *Stroke/pathology ; }, abstract = {In the past, the spinal cord was considered a hard-wired network responsible for spinal reflexes and a conduit for long-range connections. This view has changed dramatically over the past few decades. It is now recognized as a plastic structure that has the potential to adapt to changing environments. While such changes occur under physiological conditions, the most dramatic alterations take place in response to pathological events. Many of the changes that occur following such pathological events are maladaptive, but some appear to help adapt to the new conditions. Although a number of studies have been devoted to elucidating the underlying mechanisms, in humans and animal models, the etiology and pathophysiology of various diseases impacting the spinal cord are still not well understood. In this review, we summarize current understanding and outstanding challenges for a number of diseases, including spinal muscular atrophy (SMA), amyotrophic laterals sclerosis (ALS), and spinal cord injury (SCI), with occasional relations to stroke. In particular, we focus on changes resulting from SCI (and stroke), and various influencing factors such as cause, site and extent of the afflicted damage.}, } @article {pmid38175301, year = {2024}, author = {Agra Almeida Quadros, AR and Li, Z and Wang, X and Ndayambaje, IS and Aryal, S and Ramesh, N and Nolan, M and Jayakumar, R and Han, Y and Stillman, H and Aguilar, C and Wheeler, HJ and Connors, T and Lopez-Erauskin, J and Baughn, MW and Melamed, Z and Beccari, MS and Olmedo Martínez, L and Canori, M and Lee, CZ and Moran, L and Draper, I and Kopin, AS and Oakley, DH and Dickson, DW and Cleveland, DW and Hyman, BT and Das, S and Ertekin-Taner, N and Lagier-Tourenne, C}, title = {Cryptic splicing of stathmin-2 and UNC13A mRNAs is a pathological hallmark of TDP-43-associated Alzheimer's disease.}, journal = {Acta neuropathologica}, volume = {147}, number = {1}, pages = {9}, pmid = {38175301}, issn = {1432-0533}, support = {P50 AG025711/AG/NIA NIH HHS/United States ; P30 AG019610/AG/NIA NIH HHS/United States ; R01 NS080820/NS/NINDS NIH HHS/United States ; R01 AG061796/AG/NIA NIH HHS/United States ; T32 GM008666/GM/NIGMS NIH HHS/United States ; U24 NS072026/NS/NINDS NIH HHS/United States ; R01 NS112503/NS/NINDS NIH HHS/United States ; U01 AG006786/AG/NIA NIH HHS/United States ; C06 RR016574/RR/NCRR NIH HHS/United States ; T32 AG066592/AG/NIA NIH HHS/United States ; R01 AG018023/AG/NIA NIH HHS/United States ; R38 AG065762/AG/NIA NIH HHS/United States ; P01 AG003949/AG/NIA NIH HHS/United States ; R01 AG032990/AG/NIA NIH HHS/United States ; T32 AG066596/AG/NIA NIH HHS/United States ; U19 AG074879/AG/NIA NIH HHS/United States ; P30 AG062421/AG/NIA NIH HHS/United States ; U01 AG046139/AG/NIA NIH HHS/United States ; P30 AG062429/AG/NIA NIH HHS/United States ; P01 AG017216/AG/NIA NIH HHS/United States ; P30 AG072980/AG/NIA NIH HHS/United States ; }, mesh = {Humans ; *Alzheimer Disease/genetics ; *Amyotrophic Lateral Sclerosis ; DNA-Binding Proteins/genetics ; *Frontotemporal Dementia ; *Pick Disease of the Brain ; RNA Splicing ; RNA, Messenger/genetics ; Stathmin/genetics ; }, abstract = {Nuclear clearance and cytoplasmic accumulations of the RNA-binding protein TDP-43 are pathological hallmarks in almost all patients with amyotrophic lateral sclerosis (ALS) and up to 50% of patients with frontotemporal dementia (FTD) and Alzheimer's disease. In Alzheimer's disease, TDP-43 pathology is predominantly observed in the limbic system and correlates with cognitive decline and reduced hippocampal volume. Disruption of nuclear TDP-43 function leads to abnormal RNA splicing and incorporation of erroneous cryptic exons in numerous transcripts including Stathmin-2 (STMN2, also known as SCG10) and UNC13A, recently reported in tissues from patients with ALS and FTD. Here, we identify both STMN2 and UNC13A cryptic exons in Alzheimer's disease patients, that correlate with TDP-43 pathology burden, but not with amyloid-β or tau deposits. We also demonstrate that processing of the STMN2 pre-mRNA is more sensitive to TDP-43 loss of function than UNC13A. In addition, full-length RNAs encoding STMN2 and UNC13A are suppressed in large RNA-seq datasets generated from Alzheimer's disease post-mortem brain tissue. Collectively, these results open exciting new avenues to use STMN2 and UNC13A as potential therapeutic targets in a broad range of neurodegenerative conditions with TDP-43 proteinopathy including Alzheimer's disease.}, } @article {pmid38175192, year = {2024}, author = {Wu, Z and Li, H and Zhang, Z and Su, X and Shi, H and Huang, YN}, title = {Design of Deep-Ultraviolet Zero-Order Waveplate Materials by Rational Assembly of [AlO2F4] and [SO4] Groups.}, journal = {Inorganic chemistry}, volume = {63}, number = {3}, pages = {1674-1681}, doi = {10.1021/acs.inorgchem.3c03904}, pmid = {38175192}, issn = {1520-510X}, abstract = {Zero-order waveplates are widely used in the manufacture of laser polarizer waves, which are important in polarimetry and the laser industry. However, there are still challenges in designing deep-ultraviolet (DUV) waveplate materials that satisfy large band gaps and small optical anisotropy simultaneously. Herein, three cases of aluminum sulfate fluorides: Na2AlSO4F3, Li4NH4Al(SO4)2F4, and Li6K3Al(SO4)4F4, with novel [AlSO4F3] layers or isolated [AlS2O8F4] trimers were designed and synthesized by the rational assembly of [AlO2F4] and [SO4] groups through a hydrothermal method. Experiments and theoretical calculations imply that these three possess short cutoff edges (λ < 200 nm) and small birefringence (0.0014-0.0076 @ 1064 nm), which fulfils the prerequisite for potential DUV zero-order waveplate materials. This work extends the exploration of DUV zero-order waveplate materials to the aluminum sulfate fluoride systems.}, } @article {pmid38174670, year = {2023}, author = {Maksymowicz-Śliwińska, A and Lulé, D and Nieporęcki, K and Ciećwierska, K and Ludolph, AC and Kuźma-Kozakiewicz, M}, title = {Attitudes of caregivers towards prolonging and shortening life in advanced stages of amyotrophic lateral sclerosis.}, journal = {Folia neuropathologica}, volume = {61}, number = {4}, pages = {349-359}, doi = {10.5114/fn.2023.130444}, pmid = {38174670}, issn = {1509-572X}, mesh = {Humans ; Female ; Male ; *Amyotrophic Lateral Sclerosis/therapy ; Quality of Life ; Caregivers ; Death ; Disease Progression ; }, abstract = {INTRODUCTION: Inevitable disease progression in amyotrophic lateral sclerosis (ALS) forces patients and their caregivers (CGs) to reflect on end-of-life treatment. The CGs are often heavily burdened with their role of surrogate decision-makers. The aim of the study was to analyze attitudes of CGs and presumable attitudes of ALS patients from the CGs' perspective towards palliative care in advanced disease stages.

MATERIAL AND METHODS: One hundred and sixty four CGs from Germany and Poland were interviewed regarding their own preferences and patients' ideational attitudes towards life-prolonging (invasive and non-invasive ventilation, tube feeding) and life-shortening methods (termination of measures, active measures if permitted by law). The data were correlated with patient- and CG-related factors: demographic and clinical data, care commitment, depression and quality of life (QoL).

RESULTS: The CGs were mostly female spouses of ALS patients, with secondary/higher education. Nearly 70% (81% in Poland, 57% in Germany; p = 0.0001) reported positive attitudes towards life-prolonging methods, which positively correlated with religiousness and negatively with patients' age. Approximately 40% of CGs (25% and 51% respectively; p = 0.001) reported positive attitudes towards life-shortening methods. It positively correlated with time since diagnosis and negatively with the CG's QoL, religiosity and religious/spiritual faith as factors that significantly influenced end-of-life decisions. There was a strongly positive correlation between CGs' positive attitudes towards life-shortening methods and presumed positive patients' attitudes assessed by their CGs (p < 0.000001).

CONCLUSIONS: Although attitudes towards treatment differed between countries, the CGs of ALS patients were generally positive towards life-prolonging treatment. A greater acceptance of life-shortening methods in the case of longer disease duration and poorer QoL may indicate worse coping with disease progression and weaker adaptation mechanisms in CGs compared to those previously reported in ALS patients. A close resemblance of the CGs' answers to probable patients' attitudes reported by the CGs indicates that many GCs might actually express their own culturally shaped attitudes towards end-of-life methods. In light of earlier-reported discrepancies between presumed opinions of the CGs and of patients themselves, a greater focus should be placed on thorough discussions on future treatment options with ALS patients in the presence of their CGs, to stay in line with the patient's authentic will.}, } @article {pmid38174587, year = {2024}, author = {Hung, C and Patani, R}, title = {4R tau drives endolysosomal and autophagy dysfunction in frontotemporal dementia.}, journal = {Autophagy}, volume = {20}, number = {5}, pages = {1201-1202}, pmid = {38174587}, issn = {1554-8635}, support = {MR/S006591/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Humans ; *Frontotemporal Dementia/metabolism/genetics/pathology ; *Autophagy/physiology ; *tau Proteins/metabolism ; *Lysosomes/metabolism ; Endosomes/metabolism ; Neurons/metabolism ; Mutation/genetics ; Valosin Containing Protein/metabolism/genetics ; }, abstract = {Dysfunction of the neuronal endolysosome and macroautophagy/autophagy pathway is emerging as an important pathogenic mechanism in frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). The VCP (valosin-containing protein) gene is of significant relevance, directly implicated in both FTD and ALS. In our recent study, we used patient-derived stem cells to study the effects of VCP mutations on the endolysosome and autophagy system in human cortical excitatory neurons. We found that VCP mutations cause an abnormal accumulation of enlarged endosomes and lysosomes, accompanied by reduced autophagy flux. VCP mutations also lead to the spatial dissociation of intra-nuclear RNA-binding proteins, FUS and SFPQ, which correlates with alternative splicing of the MAPT pre-mRNA and increased tau phosphorylation. Importantly, we found that an increase in the 4R-tau isoform is sufficient to drive toxic changes in healthy human cortical excitatory neurons, including tau hyperphosphorylation, endolysosomal dysfunction, lysosomal membrane rupture, endoplasmic reticulum stress, and apoptosis. Together, our data suggest that endolysosomal and autophagy dysfunction could represent a convergent pathogenic "design principle" shared by both FTD and ALS.}, } @article {pmid38174271, year = {2024}, author = {Aguila-Rosas, J and García-Martínez, BA and Ríos, C and Diaz-Ruiz, A and Obeso, JL and Quirino-Barreda, CT and Ibarra, IA and Guzmán-Vargas, A and Lima, E}, title = {Copper release by MOF-74(Cu): a novel pharmacological alternative to diseases with deficiency of a vital oligoelement.}, journal = {RSC advances}, volume = {14}, number = {2}, pages = {855-862}, pmid = {38174271}, issn = {2046-2069}, abstract = {Copper deficiency can trigger various diseases such as Amyotrophic Lateral Sclerosis (ALS), Parkinson's disease (PD) and even compromise the development of living beings, as manifested in Menkes disease (MS). Thus, the regulated administration (controlled release) of copper represents an alternative to reduce neuronal deterioration and prevent disease progression. Therefore, we present, to the best of our knowledge, the first experimental in vitro investigation for the kinetics of copper release from MOF-74(Cu) and its distribution in vivo after oral administration in male Wistar rats. Taking advantage of the abundance and high periodicity of copper within the crystalline-nanostructured metal-organic framework material (MOF-74(Cu)), it was possible to control the release of copper due to the partial degradation of the material. Thus, we simultaneously corroborated a low accumulation of copper in the liver (the main detoxification organ) and a slight increase of copper in the brain (striatum and midbrain), demonstrating that MOF-74(Cu) is a promising pharmacological alternative (controlled copper source) to these diseases.}, } @article {pmid38171451, year = {2024}, author = {Halon-Golabek, M and Flis, DJ and Zischka, H and Akdogan, B and Wieckowski, MR and Antosiewicz, J and Ziolkowski, W}, title = {Amyotrophic lateral sclerosis associated disturbance of iron metabolism is blunted by swim training-role of AKT signaling pathway.}, journal = {Biochimica et biophysica acta. Molecular basis of disease}, volume = {1870}, number = {3}, pages = {167014}, doi = {10.1016/j.bbadis.2023.167014}, pmid = {38171451}, issn = {1879-260X}, mesh = {Mice ; Animals ; Humans ; Proto-Oncogene Proteins c-akt/metabolism ; *Amyotrophic Lateral Sclerosis/genetics/metabolism ; Superoxide Dismutase-1/metabolism ; *Neuroblastoma ; Signal Transduction ; Iron/metabolism ; Disease Models, Animal ; Ferritins/metabolism ; RNA-Binding Proteins/metabolism ; }, abstract = {Swim training has increased the life span of the transgenic animal model of amyotrophic lateral sclerosis (ALS). Conversely, the progress of the disease is associated with the impairment of iron metabolism and insulin signaling. We used transgenic hmSOD1 G93A (ALS model) and non-transgenic mice in the present study. The study was performed on the muscles taken from trained (ONSET and TERMINAL) and untrained animals at three stages of the disease: BEFORE, ONSET, and TERMINAL. In order to study the molecular mechanism of changes in iron metabolism, we used SH-SY5Y and C2C12 cell lines expression vector pcDNA3.1 and transiently transfected with specific siRNAs. The progress of ALS resulted in decreased P-Akt/Akt ratio, which is associated with increased proteins responsible for iron storage ferritin L, ferritin H, PCBP1, and skeletal muscle iron at ONSET. Conversely, proteins responsible for iron export- TAU significantly decrease. The training partially reverses changes in proteins responsible for iron metabolism. AKT silencing in the SH-SY5Y cell line decreased PCBP2 and ferroportin and increased ferritin L, H, PCBP1, TAU, transferrin receptor 1, and APP. Moreover, silencing APP led to an increase in ferritin L and H. Our data suggest that swim training in the mice ALS model is associated with significant changes in iron metabolism related to AKT activity. Down-regulation of AKT mainly upregulates proteins involved in iron import and storage but decreases proteins involved in iron export.}, } @article {pmid38170745, year = {2024}, author = {Aubrey, LD and Ninkina, N and Ulamec, SM and Abramycheva, NY and Vasili, E and Devine, OM and Wilkinson, M and Mackinnon, E and Limorenko, G and Walko, M and Muwanga, S and Amadio, L and Peters, OM and Illarioshkin, SN and Outeiro, TF and Ranson, NA and Brockwell, DJ and Buchman, VL and Radford, SE}, title = {Substitution of Met-38 to Ile in γ-synuclein found in two patients with amyotrophic lateral sclerosis induces aggregation into amyloid.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {121}, number = {2}, pages = {e2309700120}, pmid = {38170745}, issn = {1091-6490}, support = {MC_PC_16030/2/MRC_/Medical Research Council/United Kingdom ; P40 OD018537/OD/NIH HHS/United States ; 221524/WT_/Wellcome Trust/United Kingdom ; MR/T011149/1/MRC_/Medical Research Council/United Kingdom ; 204963/WT_/Wellcome Trust/United Kingdom ; 204963/Z/16/Z/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Animals ; Humans ; Amyloid/chemistry ; *Amyotrophic Lateral Sclerosis/genetics ; gamma-Synuclein/genetics ; alpha-Synuclein/metabolism ; *Parkinson Disease/metabolism ; Amyloidogenic Proteins ; }, abstract = {α-, β-, and γ-Synuclein are intrinsically disordered proteins implicated in physiological processes in the nervous system of vertebrates. α-synuclein (αSyn) is the amyloidogenic protein associated with Parkinson's disease and certain other neurodegenerative disorders. Intensive research has focused on the mechanisms that cause αSyn to form amyloid structures, identifying its NAC region as being necessary and sufficient for amyloid assembly. Recent work has shown that a 7-residue sequence (P1) is necessary for αSyn amyloid formation. Although γ-synuclein (γSyn) is 55% identical in sequence to αSyn and its pathological deposits are also observed in association with neurodegenerative conditions, γSyn is resilient to amyloid formation in vitro. Here, we report a rare single nucleotide polymorphism (SNP) in the SNCG gene encoding γSyn, found in two patients with amyotrophic lateral sclerosis (ALS). The SNP results in the substitution of Met38 with Ile in the P1 region of the protein. These individuals also had a second, common and nonpathological, SNP in SNCG resulting in the substitution of Glu110 with Val. In vitro studies demonstrate that the Ile38 variant accelerates amyloid fibril assembly. Contrastingly, Val110 retards fibril assembly and mitigates the effect of Ile38. Substitution of residue 38 with Leu had little effect, while Val retards, and Ala increases the rate of amyloid formation. Ile38 γSyn also results in the formation of γSyn-containing inclusions in cells. The results show how a single point substitution can enhance amyloid formation of γSyn and highlight the P1 region in driving amyloid formation in another synuclein family member.}, } @article {pmid38170440, year = {2024}, author = {Kumar, S and Mehan, S and Khan, Z and Das Gupta, G and Narula, AS}, title = {Guggulsterone Selectively Modulates STAT-3, mTOR, and PPAR-Gamma Signaling in a Methylmercury-Exposed Experimental Neurotoxicity: Evidence from CSF, Blood Plasma, and Brain Samples.}, journal = {Molecular neurobiology}, volume = {61}, number = {8}, pages = {5161-5193}, pmid = {38170440}, issn = {1559-1182}, support = {DST-SERB//DST-SERB, Govt. of India; Core Research Grant/ ; Govt. of India; Core Research Grant - CRG/2021/001009//DST-SERB, Govt. of India; Core Research Grant/ ; }, mesh = {Animals ; *TOR Serine-Threonine Kinases/metabolism ; *PPAR gamma/metabolism ; *STAT3 Transcription Factor/metabolism ; *Methylmercury Compounds/toxicity ; Male ; *Brain/drug effects/pathology/metabolism ; *Signal Transduction/drug effects ; Rats ; *Pregnenediones/pharmacology ; Rats, Wistar ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a paralytic disease that damages the brain and spinal cord motor neurons. Several clinical and preclinical studies have found that methylmercury (MeHg[+]) causes ALS. In ALS, MeHg[+]-induced neurotoxicity manifests as oligodendrocyte destruction; myelin basic protein (MBP) deficiency leads to axonal death. ALS development has been connected to an increase in signal transducer and activator of transcription-3 (STAT-3), a mammalian target of rapamycin (mTOR), and a decrease in peroxisome proliferator-activated receptor (PPAR)-gamma. Guggulsterone (GST), a plant-derived chemical produced from Commiphorawhighitii resin, has been found to protect against ALS by modulating these signaling pathways. Vitamin D3 (VitD3) deficiency has been related to oligodendrocyte precursor cells (OPC) damage, demyelination, and white matter deterioration, which results in motor neuron death. As a result, the primary goal of this work was to investigate the therapeutic potential of GST by altering STAT-3, mTOR, and PPAR-gamma levels in a MeHg[+]-exposed experimental model of ALS in adult rats. The GST30 and 60 mg/kg oral treatments significantly improved the behavioral, motor, and cognitive dysfunctions and increased remyelination, as proven by the Luxol Fast Blue stain (LFB), and reduced neuroinflammation as measured by histological examinations. Furthermore, the co-administration of VitD3 exhibits moderate efficacy when administered in combination with GST60. Our results show that GST protects neurons by decreasing STAT-3 and mTOR levels while increasing PPAR-gamma protein levels in ALS rats.}, } @article {pmid38170217, year = {2024}, author = {Zhu, Y and Burg, T and Neyrinck, K and Vervliet, T and Nami, F and Vervoort, E and Ahuja, K and Sassano, ML and Chai, YC and Tharkeshwar, AK and De Smedt, J and Hu, H and Bultynck, G and Agostinis, P and Swinnen, JV and Van Den Bosch, L and da Costa, RFM and Verfaillie, C}, title = {Disruption of MAM integrity in mutant FUS oligodendroglial progenitors from hiPSCs.}, journal = {Acta neuropathologica}, volume = {147}, number = {1}, pages = {6}, pmid = {38170217}, issn = {1432-0533}, support = {12ZG121N//Fonds Wetenschappelijk Onderzoek/ ; SBO-S001221N//Fonds Wetenschappelijk Onderzoek/ ; 12AIK24N//Fonds Wetenschappelijk Onderzoek/ ; W001422N//Fonds Wetenschappelijk Onderzoek/ ; W001422N//Fonds Wetenschappelijk Onderzoek/ ; 201908440360//China Scholarship Council/ ; C14-17-107//Universitaire Ziekenhuizen Leuven, KU Leuven/ ; C14/22/132//Universitaire Ziekenhuizen Leuven, KU Leuven/ ; ALS-OL//Fondation Thierry Latran/ ; C14/19/099//Research Council of the KU Leuven/ ; AKUL/19/34//Research Council of the KU Leuven/ ; iBOF/23/02//the ALS Liga ('A Cure for ALS')/ ; IDN/22/012//Generet Award for Rare Diseases/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/pathology ; *Induced Pluripotent Stem Cells/metabolism ; Motor Neurons/metabolism ; Mutation ; Oligodendroglia/metabolism ; RNA-Binding Protein FUS/genetics/metabolism ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a rapidly progressive and fatal neurodegenerative disorder, characterized by selective loss of motor neurons (MNs). A number of causative genetic mutations underlie the disease, including mutations in the fused in sarcoma (FUS) gene, which can lead to both juvenile and late-onset ALS. Although ALS results from MN death, there is evidence that dysfunctional glial cells, including oligodendroglia, contribute to neurodegeneration. Here, we used human induced pluripotent stem cells (hiPSCs) with a R521H or a P525L mutation in FUS and their isogenic controls to generate oligodendrocyte progenitor cells (OPCs) by inducing SOX10 expression from a TET-On SOX10 cassette. Mutant and control iPSCs differentiated efficiently into OPCs. RNA sequencing identified a myelin sheath-related phenotype in mutant OPCs. Lipidomic studies demonstrated defects in myelin-related lipids, with a reduction of glycerophospholipids in mutant OPCs. Interestingly, FUS[R521H] OPCs displayed a decrease in the phosphatidylcholine/phosphatidylethanolamine ratio, known to be associated with maintaining membrane integrity. A proximity ligation assay further indicated that mitochondria-associated endoplasmic reticulum membranes (MAM) were diminished in both mutant FUS OPCs. Moreover, both mutant FUS OPCs displayed increased susceptibility to ER stress when exposed to thapsigargin, and exhibited impaired mitochondrial respiration and reduced Ca[2+] signaling from ER Ca[2+] stores. Taken together, these results demonstrate a pathological role of mutant FUS in OPCs, causing defects in lipid metabolism associated with MAM disruption manifested by impaired mitochondrial metabolism with increased susceptibility to ER stress and with suppressed physiological Ca[2+] signaling. As such, further exploration of the role of oligodendrocyte dysfunction in the demise of MNs is crucial and will provide new insights into the complex cellular mechanisms underlying ALS.}, } @article {pmid38169680, year = {2023}, author = {Zhang, Z and Liu, N and Pan, X and Zhang, C and Yang, Y and Li, X and Shao, Y}, title = {Assessing causal associations between neurodegenerative diseases and neurological tumors with biological aging: a bidirectional Mendelian randomization study.}, journal = {Frontiers in neuroscience}, volume = {17}, number = {}, pages = {1321246}, pmid = {38169680}, issn = {1662-4548}, abstract = {BACKGROUND: Aging is a significant risk factor for many neurodegenerative diseases and neurological tumors. Previous studies indicate that the frailty index, facial aging, telomere length (TL), and epigenetic aging clock acceleration are commonly used biological aging proxy indicators. This study aims to comprehensively explore potential relationships between biological aging and neurodegenerative diseases and neurological tumors by integrating various biological aging proxy indicators, employing Mendelian randomization (MR) analysis.

METHODS: Two-sample bidirectional MR analyses were conducted using genome-wide association study (GWAS) data. Summary statistics for various neurodegenerative diseases and neurological tumors, along with biological aging proxy indicators, were obtained from extensive meta-analyses of GWAS. Genetic single-nucleotide polymorphisms (SNPs) associated with the exposures were used as instrumental variables, assessing causal relationships between three neurodegenerative diseases (Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis), two benign neurological tumors (vestibular schwannoma and meningioma), one malignant neurological tumor (glioma), and four biological aging indicators (frailty index, facial aging, TL, and epigenetic aging clock acceleration). Sensitivity analyses were also performed.

RESULTS: Our analysis revealed that genetically predicted longer TL reduces the risk of Alzheimer's disease but increases the risk of vestibular schwannoma and glioma (All Glioma, GBM, non-GBM). In addition, there is a suggestive causal relationship between some diseases (PD and GBM) and DNA methylation GrimAge acceleration. Causal relationships between biological aging proxy indicators and other neurodegenerative diseases and neurological tumors were not observed.

CONCLUSION: Building upon prior investigations into the causal relationships between telomeres and neurodegenerative diseases and neurological tumors, our study validates these findings using larger GWAS data and demonstrates, for the first time, that Parkinson's disease and GBM may promote epigenetic age acceleration. Our research provides new insights and evidence into the causal relationships between biological aging and the risk of neurodegenerative diseases and neurological tumors.}, } @article {pmid38168440, year = {2023}, author = {Ugalde, MV and Alecki, C and Rizwan, J and Le, P and Jacob-Tomas, S and Xu, JM and Minotti, S and Wu, T and Durham, H and Yeo, G}, title = {Localized molecular chaperone synthesis maintains neuronal dendrite proteostasis.}, journal = {Research square}, volume = {}, number = {}, pages = {}, pmid = {38168440}, issn = {2693-5015}, support = {RF1 MH126719/MH/NIMH NIH HHS/United States ; U41 HG009889/HG/NHGRI NIH HHS/United States ; U24 HG009889/HG/NHGRI NIH HHS/United States ; R01 HG004659/HG/NHGRI NIH HHS/United States ; R01 HG011864/HG/NHGRI NIH HHS/United States ; R01 NS103172/NS/NINDS NIH HHS/United States ; }, abstract = {Proteostasis is maintained through regulated protein synthesis and degradation and chaperone-assisted protein folding. However, this is challenging in neuronal projections because of their polarized morphology and constant synaptic proteome remodeling. Using high-resolution fluorescence microscopy, we discovered that neurons localize a subset of chaperone mRNAs to their dendrites and use microtubule-based transport to increase this asymmetric localization following proteotoxic stress. The most abundant dendritic chaperone mRNA encodes a constitutive heat shock protein 70 family member (HSPA8). Proteotoxic stress also enhanced HSPA8 mRNA translation efficiency in dendrites. Stress-mediated HSPA8 mRNA localization to the dendrites was impaired by depleting fused in sarcoma-an amyotrophic lateral sclerosis-related protein-in cultured mouse motor neurons and expressing a pathogenic variant of heterogenous nuclear ribonucleoprotein A2/B1 in neurons derived from human induced pluripotent stem cells. These results reveal a crucial and unexpected neuronal stress response in which RNA-binding proteins increase the dendritic localization of HSPA8 mRNA to maintain proteostasis and prevent neurodegeneration.}, } @article {pmid38168426, year = {2023}, author = {Talaia, G and Bentley-DeSousa, A and Ferguson, SM}, title = {Lysosomal TBK1 Responds to Amino Acid Availability to Relieve Rab7-Dependent mTORC1 Inhibition.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {38168426}, issn = {2692-8205}, support = {R01 GM105718/GM/NIGMS NIH HHS/United States ; }, abstract = {Lysosomes play a pivotal role in coordinating macromolecule degradation and regulating cell growth and metabolism. Despite substantial progress in identifying lysosomal signaling proteins, understanding the pathways that synchronize lysosome functions with changing cellular demands remains incomplete. This study uncovers a role for TANK-binding kinase 1 (TBK1), well known for its role in innate immunity and organelle quality control, in modulating lysosomal responsiveness to nutrients. Specifically, we identify a pool of TBK1 that is recruited to lysosomes in response to elevated amino acid levels. At lysosomes, this TBK1 phosphorylates Rab7 on serine 72. This is critical for alleviating Rab7-mediated inhibition of amino acid-dependent mTORC1 activation. Furthermore, a TBK1 mutant (E696K) associated with amyotrophic lateral sclerosis and frontotemporal dementia constitutively accumulates at lysosomes, resulting in elevated Rab7 phosphorylation and increased mTORC1 activation. This data establishes the lysosome as a site of amino acid regulated TBK1 signaling that is crucial for efficient mTORC1 activation. This lysosomal pool of TBK1 has broader implications for lysosome homeostasis, and its dysregulation could contribute to the pathogenesis of ALS-FTD.}, } @article {pmid38168388, year = {2023}, author = {Cheemala, A and Kimble, AL and Tyburski, JD and Leclair, NK and Zuberi, AR and Murphy, M and Jellison, ER and Reese, B and Hu, X and Lutz, CM and Yan, R and Murphy, PA}, title = {Loss of Endothelial TDP-43 Leads to Blood Brain Barrier Defects in Mouse Models of Amyotrophic Lateral Sclerosis and Frontotemporal Dementia.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {38168388}, issn = {2692-8205}, support = {R00 HL125727/HL/NHLBI NIH HHS/United States ; K99 HL125727/HL/NHLBI NIH HHS/United States ; U54 OD020351/OD/NIH HHS/United States ; P30 CA034196/CA/NCI NIH HHS/United States ; RF1 NS117449/NS/NINDS NIH HHS/United States ; }, abstract = {Loss of nuclear TDP-43 occurs in a wide range of neurodegenerative diseases, and specific mutations in the TARDBP gene that encodes the protein are linked to familial Frontal Temporal Lobar Dementia (FTD), and Amyotrophic Lateral Sclerosis (ALS). Although the focus has been on neuronal cell dysfunction caused by TDP-43 variants, TARDBP mRNA transcripts are expressed at similar levels in brain endothelial cells (ECs). Since increased permeability across the blood brain barrier (BBB) precedes cognitive decline, we postulated that altered functions of TDP-43 in ECs contributes to BBB dysfunction in neurodegenerative disease. To test this hypothesis, we examined EC function and BBB properties in mice with either knock-in mutations found in ALS/FTLD patients (TARDBP [G348C] and GRN [R493X]) or EC-specific deletion of TDP-43 throughout the endothelium (Cdh5(PAC)CreERT2; Tardbp [ff]) or restricted to brain endothelium (Slco1c1(BAC)CreERT2; Tardbp [ff]). We found that TARDBP [G348C] mice exhibited increased permeability to 3kDa Texas Red dextran and NHS-biotin, relative to their littermate controls, which could be recapitulated in cultured brain ECs from these mice. Nuclear levels of TDP-43 were reduced in vitro and in vivo in ECs from TARDBP [G348C] mice. This coincided with a reduction in junctional proteins VE-cadherin, claudin-5 and ZO-1 in isolated ECs, supporting a cell autonomous effect on barrier function through a loss of nuclear TDP-43. We further examined two models of Tardbp deletion in ECs, and found that the loss of TDP-43 throughout the endothelium led to systemic endothelial activation and permeability. Deletion specifically within the brain endothelium acutely increased BBB permeability, and eventually led to hallmarks of FTD, including fibrin deposition, microglial and astrocyte activation, and behavioral defects. Together, these data show that TDP-43 dysfunction specifically within brain ECs would contribute to the BBB defects observed early in the progression of ALS/FTLD.}, } @article {pmid38168370, year = {2023}, author = {McCallister, TX and Lim, CKW and Terpstra, WM and Alejandra Zeballos C, M and Zhang, S and Powell, JE and Gaj, T}, title = {A high-fidelity CRISPR-Cas13 system improves abnormalities associated with C9ORF72-linked ALS/FTD.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {38168370}, issn = {2692-8205}, support = {R01 GM141296/GM/NIGMS NIH HHS/United States ; R01 NS123556/NS/NINDS NIH HHS/United States ; T32 EB019944/EB/NIBIB NIH HHS/United States ; U01 NS122102/NS/NINDS NIH HHS/United States ; }, abstract = {An abnormal expansion of a GGGGCC hexanucleotide repeat in the C9ORF72 gene is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), two debilitating neurodegenerative disorders driven in part by gain-of-function mechanisms involving transcribed forms of the repeat expansion. By utilizing a Cas13 variant with reduced collateral effects, we developed a high-fidelity RNA-targeting CRISPR-based system for C9ORF72-linked ALS/FTD. When delivered to the brain of a transgenic rodent model, this Cas13-based platform effectively curbed the expression of the GGGGCC repeat-containing RNA without affecting normal C9ORF72 levels, which in turn decreased the formation of RNA foci and reversed transcriptional deficits. This high-fidelity Cas13 variant possessed improved transcriptome-wide specificity compared to its native form and mediated efficient targeting in motor neuron-like cells derived from a patient with ALS. Our results lay the foundation for the implementation of RNA-targeting CRISPR technologies for C9ORF72-linked ALS/FTD.}, } @article {pmid38168312, year = {2023}, author = {Rothstein, JD and Warlick, C and Coyne, AN}, title = {Highly variable molecular signatures of TDP-43 loss of function are associated with nuclear pore complex injury in a population study of sporadic ALS patient iPSNs.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {38168312}, issn = {2692-8205}, support = {RF1 AG062171/AG/NIA NIH HHS/United States ; P30 AG066511/AG/NIA NIH HHS/United States ; R01 NS122236/NS/NINDS NIH HHS/United States ; R35 NS132179/NS/NINDS NIH HHS/United States ; R00 NS123242/NS/NINDS NIH HHS/United States ; P01 NS084974/NS/NINDS NIH HHS/United States ; R01 NS132836/NS/NINDS NIH HHS/United States ; }, abstract = {The nuclear depletion and cytoplasmic aggregation of the RNA binding protein TDP-43 is widely considered a pathological hallmark of Amyotrophic Lateral Sclerosis (ALS) and related neurodegenerative diseases. Recent studies have artificially reduced TDP-43 in wildtype human neurons to replicate loss of function associated events. Although this prior work has defined a number of gene expression and mRNA splicing changes that occur in a TDP-43 dependent manner, it is unclear how these alterations relate to authentic ALS where TDP-43 is not depleted from the cell but miscompartmentalized to variable extents. Here, in this population study, we generate ~30,000 qRT-PCR data points spanning 20 genes in induced pluripotent stem cell (iPSC) derived neurons (iPSNs) from >150 control, C9orf72 ALS/FTD, and sALS patients to examine molecular signatures of TDP-43 dysfunction. This data set defines a time dependent and variable profile of individual molecular hallmarks of TDP-43 loss of function within and amongst individual patient lines. Importantly, nearly identical changes are observed in postmortem CNS tissues obtained from a subset of patients whose iPSNs were examined. Notably, these studies provide evidence that induction of nuclear pore complex (NPC) injury via reduction of the transmembrane Nup POM121 in wildtype iPSNs is sufficient to phenocopy disease associated signatured of TDP-43 loss of function thereby directly linking NPC integrity to TDP-43 loss of function. Therapeutically, we demonstrate that the expression of all mRNA species associated with TDP-43 loss of function can be restored in sALS iPSNs via two independent methods to repair NPC injury. Collectively, this data 1) represents a substantial resource for the community to examine TDP-43 loss of function events in authentic sALS patient iPSNs, 2) demonstrates that patient derived iPSNs can accurately reflect actual TDP-43 associated alterations in patient brain, and 3) that targeting NPC injury events can be preclinically and reliably accomplished in an iPSN based platform of a sporadic disease.}, } @article {pmid38168276, year = {2023}, author = {Omar, OMF and Kimble, AL and Cheemala, A and Tyburski, JD and Pandey, S and Wu, Q and Reese, B and Jellison, ER and Li, Y and Hao, B and Yan, R and Murphy, PA}, title = {Targeted inCITE-Seq Analysis Identifies the Loss of Nuclear TDP-43 in Endothelium as a Mediator of Blood Brain Barrier Signaling Pathway Dysfunction in Neurodegeneration.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {38168276}, issn = {2692-8205}, support = {K99 HL125727/HL/NHLBI NIH HHS/United States ; R00 HL125727/HL/NHLBI NIH HHS/United States ; R01 GM135592/GM/NIGMS NIH HHS/United States ; RF1 NS117449/NS/NINDS NIH HHS/United States ; }, abstract = {Despite the importance of the endothelium in the regulation of the blood brain barrier (BBB) in aging and neurodegenerative disease, difficulties in extracting endothelial cell (EC) nuclei have limited analysis of these cells. In addition, nearly all Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Degeneration (FTD), and a large portion of Alzheimer's Disease (AD) exhibit neuronal TDP-43 aggregation, leading to loss of nuclear function, but whether TDP-43 is similarly altered in human BBB ECs is unknown. Here we utilize a novel technique for the enrichment of endothelial and microglial nuclei from human cortical brain tissues, combined with inCITE-seq, to analyze nuclear proteins and RNA transcripts in a large cohort of healthy and diseased donors. Our findings reveal a unique transcriptional signature in nearly half of the capillary endothelial cells across neurodegenerative states, characterized by reduced levels of nuclear β-Catenin and canonical downstream genes, and an increase in TNF/NF-kB target genes. We demonstrate that this does not correlate with increased nuclear p65/NF-kB, but rather a specific loss of nuclear TDP-43 in these disease associated ECs. Comparative analysis in animal models with targeted disruption of TDP-43 shows that this is sufficient to drive these transcriptional alterations. This work reveals that TDP-43 is a critical governor of the transcriptional output from nuclear p65/NF-kB, which has paradoxical roles in barrier maintenance and also barrier compromising inflammatory responses, and suggests that disease specific loss in ECs contributes to BBB defects observed in the progression of AD, ALS and FTD.}, } @article {pmid38168171, year = {2023}, author = {Maltby, CJ and Krans, A and Grudzien, SJ and Palacios, Y and Muiños, J and Suárez, A and Asher, M and Khurana, V and Barmada, SJ and Dijkstra, AA and Todd, PK}, title = {AAGGG repeat expansions trigger RFC1-independent synaptic dysregulation in human CANVAS Neurons.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {38168171}, issn = {2692-8205}, support = {R01 NS086810/NS/NINDS NIH HHS/United States ; P50 HD104463/HD/NICHD NIH HHS/United States ; I01 BX004842/BX/BLRD VA/United States ; R01 NS113943/NS/NINDS NIH HHS/United States ; R21 NS129096/NS/NINDS NIH HHS/United States ; R01 NS097542/NS/NINDS NIH HHS/United States ; R56 NS128110/NS/NINDS NIH HHS/United States ; }, abstract = {Cerebellar ataxia with neuropathy and vestibular areflexia syndrome (CANVAS) is a late onset, recessively inherited neurodegenerative disorder caused by biallelic, non-reference pentameric AAGGG(CCCTT) repeat expansions within the second intron of replication factor complex subunit 1 (RFC1). To investigate how these repeats cause disease, we generated CANVAS patient induced pluripotent stem cell (iPSC) derived neurons (iNeurons) and utilized calcium imaging and transcriptomic analysis to define repeat-elicited gain-of-function and loss-of-function contributions to neuronal toxicity. AAGGG repeat expansions do not alter neuronal RFC1 splicing, expression, or DNA repair pathway functions. In reporter assays, AAGGG repeats are translated into pentapeptide repeat proteins that selectively accumulate in CANVAS patient brains. However, neither these proteins nor repeat RNA foci were detected in iNeurons, and overexpression of these repeats in isolation did not induce neuronal toxicity. CANVAS iNeurons exhibit defects in neuronal development and diminished synaptic connectivity that is rescued by CRISPR deletion of a single expanded allele. These phenotypic deficits were not replicated by knockdown of RFC1 in control neurons and were not rescued by ectopic expression of RFC1. These findings support a repeat-dependent but RFC1-independent cause of neuronal dysfunction in CANVAS, with important implications for therapeutic development in this currently untreatable condition.}, } @article {pmid38167886, year = {2024}, author = {Le, MUT and Park, JH and Son, JG and Shon, HK and Joh, S and Chung, CG and Cho, JH and Pirkl, A and Lee, SB and Lee, TG}, title = {Monitoring lipid alterations in Drosophila heads in an amyotrophic lateral sclerosis model with time-of-flight secondary ion mass spectrometry.}, journal = {The Analyst}, volume = {149}, number = {3}, pages = {846-858}, doi = {10.1039/d3an01670f}, pmid = {38167886}, issn = {1364-5528}, mesh = {Animals ; *Amyotrophic Lateral Sclerosis/genetics/metabolism ; Drosophila ; Spectrometry, Mass, Secondary Ion ; Lipids ; }, abstract = {Lipid alterations in the brain are well-documented in disease and aging, but our understanding of their pathogenic implications remains incomplete. Recent technological advances in assessing lipid profiles have enabled us to intricately examine the spatiotemporal variations in lipid compositions within the complex brain characterized by diverse cell types and intricate neural networks. In this study, we coupled time-of-flight secondary ion mass spectrometry (ToF-SIMS) to an amyotrophic lateral sclerosis (ALS) Drosophila model, for the first time, to elucidate changes in the lipid landscape and investigate their potential role in the disease process, serving as a methodological and analytical complement to our prior approach that utilized matrix-assisted laser desorption/ionization mass spectrometry. The expansion of G4C2 repeats in the C9orf72 gene is the most prevalent genetic factor in ALS. Our findings indicate that expressing these repeats in fly brains elevates the levels of fatty acids, diacylglycerols, and ceramides during the early stages (day 5) of disease progression, preceding motor dysfunction. Using RNAi-based genetic screening targeting lipid regulators, we found that reducing fatty acid transport protein 1 (FATP1) and Acyl-CoA-binding protein (ACBP) alleviates the retinal degeneration caused by G4C2 repeat expression and also markedly restores the G4C2-dependent alterations in lipid profiles. Significantly, the expression of FATP1 and ACBP is upregulated in G4C2-expressing flies, suggesting their contribution to lipid dysregulation. Collectively, our novel use of ToF-SIMS with the ALS Drosophila model, alongside methodological and analytical improvements, successfully identifies crucial lipids and related genetic factors in ALS pathogenesis.}, } @article {pmid38166850, year = {2024}, author = {Yu, W and Yu, F and Li, M and Yang, F and Wang, H and Song, H and Huang, X}, title = {Quantitative association between lead exposure and amyotrophic lateral sclerosis: a Bayesian network-based predictive study.}, journal = {Environmental health : a global access science source}, volume = {23}, number = {1}, pages = {2}, pmid = {38166850}, issn = {1476-069X}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/epidemiology ; Bayes Theorem ; Lead ; Retrospective Studies ; Risk Factors ; }, abstract = {BACKGROUND: Environmental lead (Pb) exposure have been suggested as a causative factor for amyotrophic lateral sclerosis (ALS). However, the role of Pb content of human body in ALS outcomes has not been quantified clearly. The purpose of this study was to apply Bayesian networks to forecast the risk of Pb exposure on the disease occurrence.

METHODS: We retrospectively collected medical records of ALS inpatients who underwent blood Pb testing, while matched controlled inpatients on age, gender, hospital ward and admission time according to the radio of 1:9. Tree Augmented Naïve Bayes (TAN), a semi-naïve Bayes classifier, was established to predict probability of ALS or controls with risk factors.

RESULTS: A total of 140 inpatients were included in this study. The whole blood Pb levels of ALS patients (57.00 μg/L) were more than twice as high as the controls (27.71 μg/L). Using the blood Pb concentrations to calculate probability of ALS, TAN produced the total coincidence rate of 90.00%. The specificity, sensitivity of Pb for ALS prediction was 0.79, or 0.74, respectively.

CONCLUSION: Therefore, these results provided quantitative evidence that Pb exposure may contribute to the development of ALS. Bayesian networks may be used to predict the ALS early onset with blood Pb levels.}, } @article {pmid38165347, year = {2024}, author = {}, title = {Observing Patterns in MRI With QSM in Patients With SOD1 Genetic ALS (5047).}, journal = {Neurology}, volume = {102}, number = {2}, pages = {e208121}, doi = {10.1212/WNL.0000000000208121}, pmid = {38165347}, issn = {1526-632X}, mesh = {Humans ; Superoxide Dismutase-1/genetics ; *Amyotrophic Lateral Sclerosis/diagnostic imaging/genetics ; Magnetic Resonance Imaging ; Patients ; }, } @article {pmid38165325, year = {2024}, author = {Spinelli, EG and Ghirelli, A and Basaia, S and Canu, E and Castelnovo, V and Cividini, C and Russo, T and Schito, P and Falzone, YM and Riva, N and Filippi, M and Agosta, F}, title = {Structural and Functional Brain Network Connectivity at Different King's Stages in Patients With Amyotrophic Lateral Sclerosis.}, journal = {Neurology}, volume = {102}, number = {2}, pages = {e207946}, pmid = {38165325}, issn = {1526-632X}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnostic imaging ; Basal Ganglia ; Brain/diagnostic imaging ; Diffusion ; Motor Neurons ; Male ; Female ; }, abstract = {BACKGROUND AND OBJECTIVES: There is currently no validated disease-stage biomarker for amyotrophic lateral sclerosis (ALS). The identification of quantitative and reproducible markers of disease stratification in ALS is fundamental for study design definition and inclusion of homogenous patient cohorts into clinical trials. Our aim was to assess the rearrangements of structural and functional brain connectivity underlying the clinical stages of ALS, to suggest objective, reproducible measures provided by MRI connectomics mirroring disease staging.

METHODS: In this observational study, patients with ALS and healthy controls (HCs) underwent clinical evaluation and brain MRI on a 3T scanner. Patients were classified into 4 groups, according to the King's staging system. Structural and functional brain connectivity matrices were obtained using diffusion tensor and resting-state fMRI data, respectively. Whole-brain network-based statistics (NBS) analysis and comparisons of intraregional and inter-regional connectivity values using analysis of covariance models were performed between groups. Correlations between MRI and clinical/cognitive measures were tested using Pearson coefficient.

RESULTS: One hundred four patients with ALS and 61 age-matched and sex-matched HCs were included. NBS and regional connectivity analyses demonstrated a progressive decrease of intranetwork and internetwork structural connectivity of sensorimotor regions at increasing ALS stages in our cohort, compared with HCs. By contrast, functional connectivity showed divergent patterns between King's stages 3 (increase in basal ganglia and temporal circuits [p = 0.04 and p = 0.05, respectively]) and 4 (frontotemporal decrease [p = 0.03]), suggesting a complex interplay between opposite phenomena in late stages of the disease. Intraregional sensorimotor structural connectivity was correlated with ALS Functional Rating Scale-revised (ALSFRS-r) score (r = 0.31, p < 0.001) and upper motor neuron burden (r = -0.25, p = 0.01). Inter-regional frontal-sensorimotor structural connectivity was also correlated with ALSFRS-r (r = 0.24, p = 0.02). No correlations with cognitive measures were found.

DISCUSSION: MRI of the brain allows to demonstrate and quantify increasing disruption of structural connectivity involving the sensorimotor networks in ALS, mirroring disease stages. Frontotemporal functional disconnection seems to characterize only advanced disease phases. Our findings support the utility of MRI connectomics to stratify patients and stage brain pathology in ALS in a reproducible way, which may mirror clinical progression.}, } @article {pmid38165299, year = {2024}, author = {Nelke, C}, title = {Right Brain: The Strangeness of a Good Diagnosis.}, journal = {Neurology}, volume = {102}, number = {3}, pages = {e208103}, doi = {10.1212/WNL.0000000000208103}, pmid = {38165299}, issn = {1526-632X}, mesh = {Humans ; Female ; Male ; *Cerebral Cortex ; *Amyotrophic Lateral Sclerosis ; Emotions ; Face ; Fasciculation ; }, abstract = {Coffee, black with a spritz of milk. I enjoyed routine, and today was no different. We were on the 12th floor of the "tower", as our hospital is lovingly called. It was my second year of residency, and I was charged with admissions to our neurological ward. Sighing with the expectation of a long day, I walked over to our patients. The first was a woman in her sixties. She complained of trouble swallowing for the past 2 months that was getting worse. She was otherwise healthy. Asked about her social background, she looked over to her husband with an impish grin and replied: "happily married for almost thirty years." Physical examination was next. There was no apparent muscle weakness, but, strangely enough, the Babinski sign was clearly positive. Looking at her tongue, I noticed a single, delicate strain of muscle twitching. It was subtle, but impossible to miss. The twitching was adamant. It was not rhythmic, but it was unrelenting. I could not help but stare, and eventually, the patient closed her mouth, looking at me puzzled. I did not make the connection at first. But, walking back to our room, I realized that the concert of neurological dysfunction was spelling out the diagnosis. I caught myself feeling excited despite my knowledge of the potential outcome. Reporting my findings to my consultant, I remember him saying: "Sure sounds like amyotrophic lateral sclerosis, but we still have to complete our work-up." And so we did, dutifully.}, } @article {pmid38165188, year = {2023}, author = {Altuwaijri, F}, title = {Simulation-based Comparison of British and Australian Advanced Life Support Guidelines.}, journal = {The western journal of emergency medicine}, volume = {24}, number = {6}, pages = {1064-1068}, pmid = {38165188}, issn = {1936-9018}, mesh = {Humans ; Australia ; *Cardiopulmonary Resuscitation/methods ; *Emergency Medical Services ; *Heart Arrest/therapy ; }, abstract = {INTRODUCTION: Cardiac arrest is a major health concern that has been linked to poor disease outcomes. Cardiopulmonary resuscitation (CPR) is a critical protocol for restoring spontaneous circulation. The guidelines used by medical staff differ across different countries. A comparison of these guidelines can help in designing more efficient Advanced Life Support (ALS) protocols. The goal in this study was to compare the guidelines for interruption of compression during CPR (hands-off time) for ALS protocols provided by Australian and United Kingdom (UK) resuscitation councils.

METHODS: The author designed a simulation-based study using a mannequin and a defibrillator, and then recruited six participants. Three participants were certified ALS practitioners who followed UK guidelines, and three were certified ALS practitioners who followed Australian guidelines. Each participant received a random task assignment for each scenario, as a team leader, performer of cardiopulmonary resuscitation, or assistant. The team leader and the chest compressor were unaware of the shockability of each case's rhythm. Eight minutes total were spent on 10 CPR trials, each lasting four cycles. A video of the simulation was recorded for automated timekeeping. An independent sample t-test was used to compare the amount of hands-off time (seconds) throughout each cycle between two procedures. For purposes of calculating statistical significance, a 0.05 P-value was employed.

RESULTS: The mean duration of second cycle hands-off time (seconds) in the UK ALS protocol was statistically significantly longer than the Australian ALS (t = -2.100; P = 0.05). For shockable rhythms, the hands-off time of the UK ALS protocol was significantly longer than Australian ALS protocol, as reflected in the second cycle (t = -0.621; P < 0.001), third cycle (t = -8.083; P < 0.001), and fourth cycle (t = -5.814; p < 0.001), while the difference in the first cycle between groups was not statistically significant. (t = -0.258; P = 0.803).

CONCLUSION: This simulation-based study demonstrated that the UK ALS guidelines led to an increased duration of hands-off time during the second cycle. The hands-off time in the shockable rhythms was also higher during the second, third, and fourth cycles in the UK ALS protocol compared to the Australian ALS protocol. These points must be focused on in future revisions of the UK ALS guidelines. For better results, it is critical to limit hands-off time between chest compression cycles.}, } @article {pmid38162906, year = {2024}, author = {Beswick, E and Forbes, D and Johnson, M and Newton, J and Dakin, R and Glasmcher, S and Abrahams, S and Carson, A and Chandran, S and Pal, S}, title = {Non-motor symptoms in motor neuron disease: prevalence, assessment and impact.}, journal = {Brain communications}, volume = {6}, number = {1}, pages = {fcad336}, pmid = {38162906}, issn = {2632-1297}, abstract = {People with motor neuron disease often experience non-motor symptoms that may occur secondary to, or distinct from, motor degeneration and that may significantly reduce quality of life, despite being under-recognized and evaluated in clinical practice. Non-motor symptoms explored in this population-based study include pain, fatigue, gastrointestinal issues, poor sleep, low mood, anxiety, problematic saliva, apathy, emotional lability, cognitive complaints and sexual dysfunction. People registered on the Clinical Audit Research and Evaluation of motor neuron disease platform, the Scottish Motor Neuron Disease Register, were invited to complete a questionnaire on non-motor symptoms and a self-reported Amyotrophic Lateral Sclerosis Functional Rating Scale. The questionnaire comprised a pre-defined list of 11 potential non-motor symptoms, with the opportunity to list additional symptoms. A total of 120 individuals participated in this cross-sectional study, a 39% response rate of those sent questionnaires (n = 311); 99% of participants recruited (n = 120) experienced at least one non-motor symptom, with 72% (n = 120) reporting five or more. The symptoms most often reported were pain and fatigue (reported by 76% of participants, respectively). The symptoms reported to be most impactful were gastrointestinal issues (reported as 'severe' by 54% of participants who experienced them), followed by pain and problematic saliva (51%, respectively). Lower Amyotrophic Lateral Sclerosis Functional Rating Scale scores, indicating more advanced disease and being a long survivor [diagnosed over 8 years ago; Black et al. (Genetic epidemiology of motor neuron disease-associated variants in the Scottish population. Neurobiol Aging. 2017;51:178.e11-178.e20.)], were significantly associated with reporting more symptoms; 73% of respondents were satisfied with the frequency that non-motor symptoms were discussed in clinical care; 80% of participants indicated they believe evaluation of non-motor symptom is important to include as outcomes in trials, independent of their personal experience of these symptoms. The preferred method of assessment was completing questionnaires, at home. The overwhelming majority of people with motor neuron disease report non-motor symptoms and these frequently co-occur. Pain, fatigue, gastrointestinal issues, sleep, mood, anxiety, problematic saliva, apathy, emotional lability, cognitive complaints and sexual dysfunction are prevalent. People with motor neuron disease who had worse physical function and those who were long survivors were more likely to report more symptoms. Where reported, these symptoms are frequent, impactful and a priority for people with motor neuron disease in clinical care and trial design.}, } @article {pmid38162899, year = {2024}, author = {Waller, R and Bury, JJ and Appleby-Mallinder, C and Wyles, M and Loxley, G and Babel, A and Shekari, S and Kazoka, M and Wollff, H and Al-Chalabi, A and Heath, PR and Shaw, PJ and Kirby, J}, title = {Establishing mRNA and microRNA interactions driving disease heterogeneity in amyotrophic lateral sclerosis patient survival.}, journal = {Brain communications}, volume = {6}, number = {1}, pages = {fcad331}, pmid = {38162899}, issn = {2632-1297}, support = {/WT_/Wellcome Trust/United Kingdom ; }, abstract = {Amyotrophic lateral sclerosis is a fatal neurodegenerative disease, associated with the degeneration of both upper and lower motor neurons of the motor cortex, brainstem and spinal cord. Death in most patients results from respiratory failure within 3-4 years from symptom onset. However, due to disease heterogeneity some individuals survive only months from symptom onset while others live for several years. Identifying specific biomarkers that aid in establishing disease prognosis, particularly in terms of predicting disease progression, will help our understanding of amyotrophic lateral sclerosis pathophysiology and could be used to monitor a patient's response to drugs and therapeutic agents. Transcriptomic profiling technologies are continually evolving, enabling us to identify key gene changes in biological processes associated with disease. MicroRNAs are small non-coding RNAs typically associated with regulating gene expression, by degrading mRNA or reducing levels of gene expression. Being able to associate gene expression changes with corresponding microRNA changes would help to distinguish a more complex biomarker signature enabling us to address key challenges associated with complex diseases such as amyotrophic lateral sclerosis. The present study aimed to investigate the transcriptomic profile (mRNA and microRNA) of lymphoblastoid cell lines from amyotrophic lateral sclerosis patients to identify key signatures that are distinguishable in those patients who suffered a short disease duration (<12 months) (n = 22) compared with those that had a longer disease duration (>6 years) (n = 20). Transcriptional profiling of microRNA-mRNA interactions from lymphoblastoid cell lines in amyotrophic lateral sclerosis patients revealed differential expression of genes involved in cell cycle, DNA damage and RNA processing in patients with longer survival from disease onset compared with those with short survival. Understanding these particular microRNA-mRNA interactions and the pathways in which they are involved may help to distinguish potential therapeutic targets that could exert neuroprotective effects to prolong the life expectancy of amyotrophic lateral sclerosis patients.}, } @article {pmid38161591, year = {2023}, author = {Li, J and Ma, C and Huang, H and Liao, H}, title = {Amyotrophic lateral sclerosis and osteoporosis: a two-sample Mendelian randomization study.}, journal = {Frontiers in aging neuroscience}, volume = {15}, number = {}, pages = {1305040}, pmid = {38161591}, issn = {1663-4365}, abstract = {BACKGROUND: A few observational studies revealed that amyotrophic lateral sclerosis (ALS) was tightly connected with osteoporosis. However, the results of previous studies were inconsistent, and the causal effect of ALS on osteoporosis has not been investigated. To do so, the two-sample Mendelian randomization (MR) method was employed to estimate the causality.

METHODS: The instrumental variables (IVs) for ALS were selected from one GWAS summary dataset (27,205 ALS cases and 110,881 controls), and bone mineral density (BMD) in the femoral neck (FN), lumbar spine (LS), and forearm, extracted from another large-scale GWAS summary database (53,236 cases), were used as phenotypes for osteoporosis. Random-effects inverse variance weighted (IVW), MR Egger, weighted median, simple mode, and weighted mode were conducted to evaluate the causality. Sensitivity analyses were further performed to explore heterogeneity and pleiotropy.

RESULTS: A total of 10 qualified SNPs were finally selected as proxies for ALS. The results of random effects from IVW revealed that ALS has no causal effect on FN-BMD (beta: -0.038, 95% CI: -0.090 to 0.015, SE: 0.027, p = 0.158), LS-BMD (beta: -0.015, 95% CI: -0.076 to 0.046, SE: 0.031, p = 0.629), and forearm BMD (beta: 0.044, 95% CI: -0.063 to 0.152, SE: 0.055, p = 0.418). These results were confirmed using the MR-Egger, weighted median, simple model, and weighted model. No heterogeneity or pleiotropy was detected (p > 0.05 for all).

CONCLUSION: Contrary to previous observational studies, our study figured out that no causal effect existed between ALS and osteoporosis. The disparity in results is probably attributed to secondary effects such as physical inactivity and muscle atrophy caused by ALS.}, } @article {pmid38160320, year = {2024}, author = {Mohanty, P and Rizuan, A and Kim, YC and Fawzi, NL and Mittal, J}, title = {A complex network of interdomain interactions underlies the conformational ensemble of monomeric TDP-43 and modulates its phase behavior.}, journal = {Protein science : a publication of the Protein Society}, volume = {33}, number = {2}, pages = {e4891}, pmid = {38160320}, issn = {1469-896X}, support = {R01 NS116176/NS/NINDS NIH HHS/United States ; /NH/NIH HHS/United States ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics ; Protein Domains ; *Frontotemporal Dementia ; DNA-Binding Proteins/chemistry ; RNA/metabolism ; }, abstract = {TAR DNA-binding protein 43 (TDP-43) is a multidomain protein involved in the regulation of RNA metabolism, and its aggregates have been observed in neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Numerous studies indicate TDP-43 can undergo liquid-liquid phase separation (LLPS) in vitro and is a component of biological condensates. Homo-oligomerization via the folded N-terminal domain (aa:1-77) and the conserved helical region (aa:319-341) of the disordered, C-terminal domain is found to be an important driver of TDP-43 phase separation. However, a comprehensive molecular view of TDP-43 phase separation, particularly regarding the nature of heterodomain interactions, is lacking due to the challenges associated with its stability and purification. Here, we utilize all-atom and coarse-grained (CG) molecular dynamics (MD) simulations to uncover the network of interdomain interactions implicated in TDP-43 phase separation. All-atom simulations uncovered the presence of transient, interdomain interactions involving flexible linkers, RNA-recognition motif (RRM) domains and a charged segment of disordered C-terminal domain (CTD). CG simulations indicate these inter-domain interactions which affect the conformational landscape of TDP-43 in the dilute phase are also prevalent in the condensed phase. Finally, sequence and surface charge distribution analysis coupled with all-atom simulations (at high salt) confirmed that the transient interdomain contacts are predominantly electrostatic in nature. Overall, our findings from multiscale simulations lead to a greater appreciation of the complex interaction network underlying the structural landscape and phase separation of TDP-43.}, } @article {pmid38159460, year = {2024}, author = {Soontrapa, P and Seven, NA and Liewluck, T and Cui, G and Mer, G and Milone, M}, title = {Adolescent-onset multisystem proteinopathy due to a novel VCP variant.}, journal = {Neuromuscular disorders : NMD}, volume = {34}, number = {}, pages = {89-94}, doi = {10.1016/j.nmd.2023.11.014}, pmid = {38159460}, issn = {1873-2364}, mesh = {Adolescent ; Adult ; Child ; Humans ; Cell Cycle Proteins/genetics ; *Muscular Diseases ; Mutation/genetics ; *Myositis, Inclusion Body/diagnosis/genetics/pathology ; *Osteitis Deformans/diagnosis/genetics/pathology ; *Proteostasis Deficiencies ; Valosin Containing Protein/genetics ; }, abstract = {Valosin-containing protein (VCP) pathogenic variants are the most common cause of multisystem proteinopathy presenting with inclusion body myopathy, amyotrophic lateral sclerosis/frontotemporal dementia, and Paget disease of bone in isolation or in combination. We report a patient manifesting with adolescent-onset myopathy caused by a novel heterozygous VCP variant (c.467G > T, p.Gly156Val). The myopathy manifested asymmetrically in lower limbs and extended to proximal, axial, and upper limb muscles, with loss of ambulation at age 35. Creatine kinase value was normal. Alkaline phosphatase was elevated. Electromyography detected mixed low amplitude, short duration and high amplitude, long duration motor unit potentials. Muscle biopsy showed features of inclusion body myopathy, which in combination with newly diagnosed Paget disease of bone, supported the VCP variant pathogenicity. In conclusion, VCP-multisystem proteinopathy is not only a disease of adulthood but can have a pediatric onset and should be considered in differential diagnosis of neuromuscular weakness in the pediatric population.}, } @article {pmid38159307, year = {2024}, author = {Lalechère, E and Monnet, JM and Breen, J and Fuhr, M}, title = {Assessing the potential of remote sensing-based models to predict old-growth forests on large spatiotemporal scales.}, journal = {Journal of environmental management}, volume = {351}, number = {}, pages = {119865}, doi = {10.1016/j.jenvman.2023.119865}, pmid = {38159307}, issn = {1095-8630}, mesh = {*Ecosystem ; Remote Sensing Technology ; Retrospective Studies ; *Biological Phenomena ; }, abstract = {Old-growth forests provide a broad range of ecosystem services. However, due to poor knowledge of their spatiotemporal distribution, implementing conservation and restoration strategies is challenging. The goal of this study is to compare the predictive ability of socioecological factors and different sources of remotely sensed data that determine the spatiotemporal scales at which forest maturity attributes can be predicted. We evaluated various remotely sensed data that cover a broad range of spatial (from local to global) and temporal (from current to decades) extents, from Airborne Laser Scanning (ALS), aerial multispectral and stereo-imagery, Sentinel-1, Sentinel-2 and Landsat data. Using random forests, remotely sensed data were related to a forest maturity index available in 688 forest plots across four ranges of the French Alps. Each model also includes socioecological predictors related to topography, socioeconomy, pedology and climatology. We found that the different remotely sensed data provide information on the main forest structural characteristics as defined by ALS, except for Landsat, which has a too coarse resolution, and Sentinel-1, which responds differently to vegetation structure. The predictions were quite similar considering aerial remotely sensed data, on the one hand, and satellite remotely sensed data, on the other hand. Socioecological variables are the most important predictors compared to the remote sensing metrics. In conclusion, our results indicate that a wide range of remotely sensed data can be used to study old-growth forests beyond the use of ALS and despite different abilities to predict forest structure. Accounting for socioecological predictors is indispensable to avoid a significant loss of predictive accuracy. Remotely sensed data can allow for predictions to be made at different spatiotemporal resolutions and extents. This study paves the way to large-scale monitoring of forest maturity, as well as for retrospective analyses which will show to what extent predicted maturity change at different dates.}, } @article {pmid38158701, year = {2024}, author = {Izumi, R and Ikeda, K and Niihori, T and Suzuki, N and Shirota, M and Funayama, R and Nakayama, K and Warita, H and Tateyama, M and Aoki, Y and Aoki, M}, title = {Nuclear pore pathology underlying multisystem proteinopathy type 3-related inclusion body myopathy.}, journal = {Annals of clinical and translational neurology}, volume = {11}, number = {3}, pages = {577-592}, pmid = {38158701}, issn = {2328-9503}, support = {KAKENHI (20K16571)//Grant-in-Aid for Early-Career Scientists from Japan Society for the Promotion of Science (JSPS)/ ; KAKENHI (20H03586)//Grant-in-Aid for Scientific Research (B) from Japan Society for the Promotion of Science (JSPS)/ ; KAKENHI (23H02821)//Grant-in-Aid for Scientific Research (B) from Japan Society for the Promotion of Science (JSPS)/ ; KAKENHI (20K07897)//Grant-in-Aid for Scientific Research (C) from Japan Society for the Promotion of Science (JSPS)/ ; 23FC1008//Grants-in-Aid from the Research Committee of CNS Degenerative Diseases, Research on Policy Planning and Evaluation for Rare and Intractable Diseases, Health, Labour and Welfare Sciences Research Grants, the Ministry of Health, Labour and Welfare, Japan/ ; 23FC1010//Grants-in-Aid from the Research Committee of CNS Degenerative Diseases, Research on Policy Planning and Evaluation for Rare and Intractable Diseases, Health, Labour and Welfare Sciences Research Grants, the Ministry of Health, Labour and Welfare, Japan/ ; 20FC1036//Grants-in-Aid for Research on Rare and Intractable Diseases from the Ministry of Health, Labour and Welfare of Japan/ ; 23FC1014//Grants-in-Aid for Research on Rare and Intractable Diseases from the Ministry of Health, Labour and Welfare of Japan/ ; //Haruki ALS Research Foundation/ ; 2-5//Intramural Research Grant for Neurological and Psychiatric Disorders Provided from National Center of Neurology and Psychiatry of Japan/ ; 5-6//Intramural Research Grant for Neurological and Psychiatric Disorders Provided from National Center of Neurology and Psychiatry of Japan/ ; }, mesh = {Humans ; *Heterogeneous-Nuclear Ribonucleoprotein Group A-B/genetics/metabolism ; *Amyotrophic Lateral Sclerosis/genetics ; Nuclear Pore/metabolism/pathology ; Muscle, Skeletal/metabolism ; Inclusion Bodies/metabolism/pathology ; *Muscular Diseases/metabolism ; Nuclear Pore Complex Proteins/genetics/metabolism ; }, abstract = {OBJECTIVE: Multisystem proteinopathy type 3 (MSP3) is an inherited, pleiotropic degenerative disorder caused by a mutation in heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1), which can affect the muscle, bone, and/or nervous system. This study aimed to determine detailed histopathological features and transcriptomic profile of HNRNPA1-mutated skeletal muscles to reveal the core pathomechanism of hereditary inclusion body myopathy (hIBM), a predominant phenotype of MSP3.

METHODS: Histopathological analyses and RNA sequencing of HNRNPA1-mutated skeletal muscles harboring a c.940G > A (p.D314N) mutation (NM_031157) were performed, and the results were compared with those of HNRNPA1-unlinked hIBM and control muscle tissues.

RESULTS: RNA sequencing revealed aberrant alternative splicing events that predominantly occurred in myofibril components and mitochondrial respiratory complex. Enrichment analyses identified the nuclear pore complex (NPC) and nucleocytoplasmic transport as suppressed pathways. These two pathways were linked by the hub genes NUP50, NUP98, NUP153, NUP205, and RanBP2. In immunohistochemistry, these nucleoporin proteins (NUPs) were mislocalized to the cytoplasm and aggregated mostly with TAR DNA-binding protein 43 kDa and, to a lesser extent, with hnRNPA1. Based on ultrastructural observation, irregularly shaped myonuclei with deep invaginations were frequently observed in atrophic fibers, consistent with the disorganization of NPCs. Additionally, regarding the expression profiles of overall NUPs, reduced expression of NUP98, NUP153, and RanBP2 was shared with HNRNPA1-unlinked hIBMs.

INTERPRETATION: The shared subset of altered NUPs in amyotrophic lateral sclerosis (ALS), as demonstrated in prior research, HNRNPA1-mutated, and HNRNPA1-unlinked hIBM muscle tissues may provide evidence regarding the underlying common nuclear pore pathology of hIBM, ALS, and MSP.}, } @article {pmid38158673, year = {2023}, author = {Luo, S and Yang, L and Ma, B and Wang, X and Lu, Y and Ma, S and Wang, D and Qu, H and Zou, L}, title = {Explore the pharmacological basis of ShengJiYiSui decoction in the treatment of amyotrophic lateral sclerosis based on network pharmacology and molecular docking technology.}, journal = {Cellular and molecular biology (Noisy-le-Grand, France)}, volume = {69}, number = {13}, pages = {156-161}, doi = {10.14715/cmb/2023.69.13.24}, pmid = {38158673}, issn = {1165-158X}, mesh = {Humans ; Network Pharmacology ; *Amyotrophic Lateral Sclerosis/drug therapy/genetics ; Molecular Docking Simulation ; Phosphatidylinositol 3-Kinases/genetics ; Proto-Oncogene Proteins c-akt ; Medicine, Chinese Traditional ; Technology ; *Drugs, Chinese Herbal/pharmacology/therapeutic use ; }, abstract = {Neurodegenerative illnesses have long been handled clinically by traditional Chinese medicine. This study is the first time to explore the pharmacological basis of application in amyotrophic lateral sclerosis (ALS) through network pharmacology and molecular docking techniques. In the present investigation, the TCMSP database and HIT2 database were examined for 9 TCM constituents of Sheng Ji Yu Sui Decoction (SJYSD), and the desired sites for the components were searched in the Drugbank database. and the Sjysd-target network was constructed. Associated targets for Amyotrophic lateral sclerosis (ALS) were then retrieved and collected in the OMIM, TTD, Genecards and DisGeNET databases. Protein-protein interaction and enrichment analysis were performed for the common targets of drugs and diseases, and molecular anchoring for the chosen core targets and related molecules was carried out. The results showed that SJYSD had 100 active compounds corresponding to 598 targets. ALS has a total of 5,325 genes. SJYSD and ALS share 163 genes, and these targets involve PI3K-AKT signaling, p53 signaling and IL-17 signaling, etc. The core components of luteolin and quercetin were discovered and may be used to treat ALS by regulating PI3K-AKT signaling pathway by HSP90AB1 protein.}, } @article {pmid38157654, year = {2024}, author = {Halseth, M and Mahoney, R and Hsiou, J and Jones, HN and Kimonis, V}, title = {Remote respiratory resistance exercise training improves respiratory function in individuals with VCP multisystem proteinopathy.}, journal = {Neuromuscular disorders : NMD}, volume = {34}, number = {}, pages = {68-74}, doi = {10.1016/j.nmd.2023.12.001}, pmid = {38157654}, issn = {1873-2364}, mesh = {Adult ; Humans ; Valosin Containing Protein/genetics ; *Resistance Training ; *Muscular Diseases ; Respiration ; *Frontotemporal Dementia ; *Amyotrophic Lateral Sclerosis ; Mutation ; Cell Cycle Proteins/genetics ; }, abstract = {Valosin-containing protein (VCP) disease is an autosomal dominant multisystem proteinopathy associated with hereditary inclusion body myopathy, Paget disease of bone, and frontotemporal dementia. Myopathy frequently results in respiratory muscle weakness, leading to early mortality due to respiratory failure. We investigated the effects of a remotely administered inspiratory muscle training program in individuals with VCP disease. Nine adults with VCP mutation-positive familial myopathy without evidence of dementia were recruited for a 40-week remotely administered study. Baseline performance was established during the first 8 weeks, followed by 32 weeks of inspiratory muscle training. The primary outcome was maximum inspiratory pressure (MIP). The secondary and exploratory endpoints included spirometry, grip strength, Inclusion Body Myopathy Functional Rating Scale (IBMFRS), Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS), timed up and go, and six-minute walk test (6MWT). During the treatment phase, MIP increased significantly by a weekly mean of 0.392cm. H2O (p=0.023). In contrast, grip strength and ALSFRS significantly decreased by 0.088 lbs. (p=0.031) and 0.043 points (p=0.004) per week, respectively, as expected from the natural progression of this disease. A remotely administered inspiratory muscle training program is therefore feasible, safe, and well-tolerated in individuals with VCP disease and results in improved inspiratory muscle strength.}, } @article {pmid38157256, year = {2023}, author = {Kang, Q and Jiang, S and Min, J and Hu, F and Xu, R}, title = {Parvalbumin interneurons dysfunction is potentially associated with FαMNs decrease and NRG1-ErbB4 signaling inhibition in spinal cord in amyotrophic lateral sclerosis.}, journal = {Aging}, volume = {15}, number = {24}, pages = {15324-15339}, pmid = {38157256}, issn = {1945-4589}, mesh = {Animals ; Mice ; *Amyotrophic Lateral Sclerosis/metabolism ; *Interneurons/metabolism ; Matrix Metalloproteinase 9/metabolism ; Mice, Transgenic ; Parvalbumins/metabolism ; Receptor, ErbB-4/genetics/metabolism ; Neuregulin-1/genetics/metabolism ; }, abstract = {OBJECTIVE: To investigate the alteration of PV interneurons in ALS mainly focusing its dynamic changes and its relationship with motor neurons and ErbB4 signaling.

METHODS: SOD1G93A mice were used as ALS model. ALS animals were divided into different groups according to birth age: symptomatic prophase (50~60 days), symptomatic phase (90~100 days), and symptomatic progression (130~140 days). Immunofluorescence was performed for measurement of PV-positive interneurons, MMP-9, ChAT, NeuN and ErbB4. RT-qPCR and western blot were used to determine the expression of PV and MMP-9.

RESULTS: PV expression was remarkably higher in the anterior horn of gray matter compared with posterior horn and area in the middle of gray matter in control mice. In ALS mice, PV, MMP-9 and ErbB4 levels were gradually decreased along with onset. PV, MMP-9 and ErbB4 levels in ALS mice were significantly down-regulated than control mice after onset, indicating the alteration of PV interneurons, FαMNs and ErbB4. SαMNs levels only decreased remarkably at symptomatic progression in ALS mice compared with control mice, while γMNs levels showed no significant change during whole period in all mice. MMP-9 and ErbB4 were positively correlated with PV. NRG1 treatment significantly enhanced the expression of ErBb4, PV and MMP-9 in ALS mice.

CONCLUSION: PV interneurons decrease is along with FαMNs and ErbB4 decrease in ALS mice.}, } @article {pmid38156828, year = {2024}, author = {Gebrehiwet, P and Brekke, J and Rudnicki, SA and Mellor, J and Wright, J and Earl, L and Ball, N and Iqbal, H and Thomas, O and Castellano, G}, title = {Time from amyotrophic lateral sclerosis symptom onset to key disease milestones: analysis of data from a multinational cross-sectional survey.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {25}, number = {3-4}, pages = {345-357}, doi = {10.1080/21678421.2023.2297795}, pmid = {38156828}, issn = {2167-9223}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/epidemiology ; Disease Progression ; Cross-Sectional Studies ; Body Mass Index ; Time Factors ; }, abstract = {OBJECTIVE: To determine the average time from Amyotrophic Lateral Sclerosis (ALS) symptom onset to 11 pre-defined milestones, overall and according to ALS progression rate and geographic location.

METHODS: Data were drawn from the Adelphi Real World ALS Disease-Specific Programme[TM], a point-in-time survey of neurologists caring for people living with ALS (pALS) conducted in France, Germany, Italy, Spain, the United Kingdom and the United States from 2020-2021. ALS progression rate was calculated using time since symptom onset and ALS Functional Rating Scale Revised score.

RESULTS: Survey results were available for N = 1003 pALS (progression rate for N = 867). Mean time from symptom onset was 3.8 months to first consultation, 8.0 months to diagnosis, 16.2 months to employment change (part-time/sick leave/retirement/unemployment), 17.5 months to use of a walking aid, 18.5 months to first occurrence of caregiver support, 22.8 months to use of a wheelchair, 24.6 months to use of a communication aid, 27.3 months to use of a respiratory aid, 28.6 months to use of gastrostomy feeding, 29.7 months to use of eye gaze technology and 30.3 months to entering a care facility. Multivariate analysis indicated significant effects of fast (versus slow) progression rate on time to reach all 11 milestones, as well as US (versus European) location, age, body mass index and bulbar onset (versus other) on time to reach milestones.

CONCLUSIONS: pALS rapidly reached clinical and disease-related milestones within 30 months from symptom onset. Milestones were reached significantly faster by pALS with fast versus slow progression. Geographic differences were observed.}, } @article {pmid38156274, year = {2023}, author = {Zheng, Q and Wang, D and Lin, R and Chen, Y and Huang, H and Xu, Z and Zheng, C and Xu, W}, title = {Mendelian randomization analysis suggests no associations of human herpes viruses with amyotrophic lateral sclerosis.}, journal = {Frontiers in neuroscience}, volume = {17}, number = {}, pages = {1299122}, pmid = {38156274}, issn = {1662-4548}, abstract = {BACKGROUND: The causal associations between infections with human herpes viruses (HHVs) and amyotrophic lateral sclerosis (ALS) has been disputed. This study investigated the causal associations between herpes simplex virus (HSV), varicella-zoster virus (VZV), Epstein-Barr virus (EBV), cytomegalovirus (CMV), HHV-6, and HHV-7 infections and ALS through a bidirectional Mendelian randomization (MR) method.

METHODS: The genome-wide association studies (GWAS) database were analyzed by inverse variance weighted (IVW), MR-Egger, weighted median, simple mode, and weighted mode methods. MR-Egger intercept test, MR-PRESSO test, Cochran's Q test, funnel plots, and leaveone-out analysis were used to verify the validity and robustness of the MR results.

RESULTS: In the forward MR analysis of the IVW, genetically predicted HSV infections [odds ratio (OR) = 0.9917; 95% confidence interval (CI): 0.9685-1.0154; p = 0.4886], HSV keratitis and keratoconjunctivitis (OR = 0.9897; 95% CI: 0.9739-1.0059; p = 0.2107), anogenital HSV infection (OR = 1.0062; 95% CI: 0.9826-1.0304; p = 0.6081), VZV IgG (OR = 1.0003; 95% CI: 0.9849-1.0160; p = 0.9659), EBV IgG (OR = 0.9509; 95% CI: 0.8879-1.0183; p = 0.1497), CMV (OR = 0.9481; 95% CI: 0.8680-1.0357; p = 0.2374), HHV-6 IgG (OR = 0.9884; 95% CI: 0.9486-1.0298; p = 0.5765) and HHV-7 IgG (OR = 0.9991; 95% CI: 0.9693-1.0299; p = 0.9557) were not causally associated with ALS. The reverse MR analysis of the IVW revealed comparable findings, indicating no link between HHVs infections and ALS. The reliability and validity of the findings were verified by the sensitivity analysis.

CONCLUSION: According to the MR study, there is no evidence of causal associations between genetically predicted HHVs (HSV, VZV, EBV, CMV, HHV-6, and HHV-7) and ALS.}, } @article {pmid38154301, year = {2024}, author = {Li, X and Gao, X and Fu, B and Lu, C and Han, H and Zhou, Q and Xu, H}, title = {Study on the toxicity prediction model ofacetolactate synthase inhibitor herbicides based on human serum albumin and superoxide dismutase binding information.}, journal = {Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy}, volume = {309}, number = {}, pages = {123789}, doi = {10.1016/j.saa.2023.123789}, pmid = {38154301}, issn = {1873-3557}, mesh = {Animals ; Humans ; *Herbicides/toxicity/metabolism ; Serum Albumin, Human/metabolism ; Molecular Docking Simulation ; *Pesticides ; Protein Binding ; Enzyme Inhibitors/toxicity ; Carrier Proteins ; Superoxide Dismutase/metabolism ; Spectrometry, Fluorescence ; }, abstract = {Toxicity significantly influences the successful development of drugs. Based on the toxicity prediction method (carrier protein binding information-toxicity relationship) previously established by the our group, this paper introduces information on the interaction between pesticides and environmental markers (SOD) into the model for the first time, so that the toxicity prediction model can not only predict the toxicity of pesticides to humans and animals, but also predict the toxicity of pesticides to the environment. Firstly, the interaction of acetolactate synthase inhibitor herbicides (ALS inhibitor herbicides) with human serum albumin (HSA) and superoxide dismutase (SOD) was investigated systematically from theory combined with experiments by spectroscopy methods and molecular docking, and important fluorescence parameters were obtained. Then, the fluorescence parameters, pesticides acute toxicity LD50 and structural splitting information were used to construct predictive modeling of ALS inhibitor herbicides based on the carrier protein binding information (R[2] = 0.977) and the predictive modeling of drug acute toxicity based on carrier protein binding information and conformational relationship (R[2] = 0.991), which had effectively predicted pesticides toxicity in humans and animals. To predict potential environmental toxicity, the predictive modeling of drug acute toxicity based on superoxide dismutase binding information was established (R[2] = 0.883) by ALS inhibitor herbicides-SOD binding information, which has a good predictive ability in the potential toxicity of pesticides to the environment. This study lays the foundation for developing low toxicity pesticides.}, } @article {pmid38152653, year = {2023}, author = {Vacchiano, V and Palombo, F and Ormanbekova, D and Fiorini, C and Fiorentino, A and Caporali, L and Mastrangelo, A and Valentino, ML and Capellari, S and Liguori, R and Carelli, V}, title = {The genetic puzzle of a SOD1-patient with ocular ptosis and a motor neuron disease: a case report.}, journal = {Frontiers in genetics}, volume = {14}, number = {}, pages = {1322067}, pmid = {38152653}, issn = {1664-8021}, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with a complex genetic architecture, showing monogenic, oligogenic, and polygenic inheritance. In this study, we describe the case of a 71 years-old man diagnosed with ALS with atypical clinical features consisting in progressive ocular ptosis and sensorineural deafness. Genetic analyses revealed two heterozygous variants, in the SOD1 (OMIM*147450) and the TBK1 (OMIM*604834) genes respectively, and furthermore mitochondrial DNA (mtDNA) sequencing identified the homoplasmic m.14484T>C variant usually associated with Leber's Hereditary Optic Neuropathy (LHON). We discuss how all these variants may synergically impinge on mitochondrial function, possibly contributing to the pathogenic mechanisms which might ultimately lead to the neurodegenerative process, shaping the clinical ALS phenotype enriched by adjunctive clinical features.}, } @article {pmid38152548, year = {2023}, author = {Neurology, B}, title = {Retracted: Classification of Myopathy and Amyotrophic Lateral Sclerosis Electromyograms Using Bat Algorithm and Deep Neural Networks.}, journal = {Behavioural neurology}, volume = {2023}, number = {}, pages = {9769130}, pmid = {38152548}, issn = {1875-8584}, abstract = {[This retracts the article DOI: 10.1155/2022/3517872.].}, } @article {pmid38151890, year = {2024}, author = {Talebi, S and Khodagholi, F and Bahaeddin, Z and Ansari Dezfouli, M and Zeinaddini-Meymand, A and Berchi Kankam, S and Foolad, F and Alijaniha, F and Fayazi Piranghar, F}, title = {Does hazelnut consumption affect brain health and function against neurodegenerative diseases?.}, journal = {Nutritional neuroscience}, volume = {27}, number = {9}, pages = {1008-1024}, doi = {10.1080/1028415X.2023.2296164}, pmid = {38151890}, issn = {1476-8305}, mesh = {*Corylus ; Humans ; *Neurodegenerative Diseases/prevention & control ; *Brain ; Nuts ; Antioxidants/administration & dosage ; Neuroprotective Agents/administration & dosage ; Animals ; Diet ; Nutritive Value ; }, abstract = {INTRODUCTION: A healthy daily diet and consuming certain nutrients, such as polyphenols, vitamins, and unsaturated fatty acids, may help neuronal health maintenance. Polyphenolic chemicals, which have antioxidant and anti-inflammatory properties, are involved in the neuroprotective pathway. Because of their nutritional value, nuts have been shown in recent research to be helpful in neuroprotection.

OBJECTIVE: Hazelnut is often consumed worldwide in various items, including processed foods, particularly in bakery, chocolate, and confectionery products. This nut is an excellent source of vitamins, amino acids, tocopherols, phytosterols, polyphenols, minerals, and unsaturated fatty acids. Consuming hazelnut may attenuate the risk of neurodegenerative disorders including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis, and Huntington's disease due to its anti-inflammatory and anti-oxidant qualities.

RESULTS: Many documents introduce hazelnut as an excellent choice to provide neuroprotection against neurodegenerative disorders and there is some direct proof of its neuroprotective effects.

DISCUSSION: So hazelnut consumption in daily diet may reduce neurodegenerative disease risk and be advantageous in reducing the imposed costs of dealing with neurodegenerative diseases.}, } @article {pmid38151605, year = {2024}, author = {Molin, J and Hartmann, J and Pærregaard, MM and Thygesen, CB and Sillesen, AS and Raja, AA and Vøgg, ROB and Iversen, KK and Bundgaard, H and Christensen, AH}, title = {The Neonatal QRS Complex and Its Association with Left Ventricular Mass.}, journal = {Pediatric cardiology}, volume = {45}, number = {2}, pages = {248-256}, pmid = {38151605}, issn = {1432-1971}, support = {NNF20OC0065799//The Novo Nordisk Foundation/ ; Grant 0134-00363B//The Independent Research Fund Denmark/ ; }, mesh = {Male ; Infant, Newborn ; Humans ; Female ; *Hypertrophy, Left Ventricular/diagnosis ; Prospective Studies ; *Electrocardiography/methods ; Heart ; Echocardiography ; }, abstract = {To evaluate QRS complex features during the first month of life and the association with echocardiographic measurements of left ventricular mass in neonates. Prospective cohort study of neonates with electrocardiography (ECG) and echocardiography performed during the first month of life. Left ventricular mass index (LVMI) was determined by echocardiography and the correlation with electrocardiographic markers of LVMI outliers (≥ 98th percentile) were analyzed. We included 17,450 neonates (52% boys; median age at examination 11 days) and found an increase in median QRS duration and LVMI during the first month of life (54 vs. 56 ms and 24.7 vs. 28.6 g/m[2] at days 0-4 and 25-30, respectively; both p < 0.001). All investigated ECG features (QRS duration, QRS area in V1/V6, maximum amplitudes of S-V1/R-V6, and the Sokolow-Lyon voltage product) showed no to low correlation with LVMI, resulting in low sensitivities (0-9.0%), but high specificities (97.2-98.1%), and area under the curve values close to the identity line (0.49-0.61) for identifying LVMI outliers. Adjustment of outlier definition for LVMI and threshold for QRS features had no significant effect on sensitivity. We present reference values for QRS complex features and their association with LVMI in neonates from a large, unselected, population-based cohort. The QRS complex gradually evolved during the first month of life but had a low correlation with LVMI. Our results indicate a poor diagnostic value of using ECG features to identify LVMI outliers in neonates.Trial Registry Copenhagen Baby Heart, NCT02753348, https://clinicaltri-als.gov/ct2/show/NCT02753348?cond=Copenhagen+Baby+Heart&draw=2&rank=1 , deidentified individual participant data will not be made available.}, } @article {pmid38151482, year = {2024}, author = {Taha, MA and Morren, JA}, title = {The role of artificial intelligence in electrodiagnostic and neuromuscular medicine: Current state and future directions.}, journal = {Muscle & nerve}, volume = {69}, number = {3}, pages = {260-272}, doi = {10.1002/mus.28023}, pmid = {38151482}, issn = {1097-4598}, mesh = {Humans ; *Artificial Intelligence ; Machine Learning ; *Amyotrophic Lateral Sclerosis/diagnostic imaging ; Brain ; Electromyography ; }, abstract = {The rapid advancements in artificial intelligence (AI), including machine learning (ML), and deep learning (DL) have ushered in a new era of technological breakthroughs in healthcare. These technologies are revolutionizing the way we utilize medical data, enabling improved disease classification, more precise diagnoses, better treatment selection, therapeutic monitoring, and highly accurate prognostication. Different ML and DL models have been used to distinguish between electromyography signals in normal individuals and those with amyotrophic lateral sclerosis and myopathy, with accuracy ranging from 67% to 99.5%. DL models have also been successfully applied in neuromuscular ultrasound, with the use of segmentation techniques achieving diagnostic accuracy of at least 90% for nerve entrapment disorders, and 87% for inflammatory myopathies. Other successful AI applications include prediction of treatment response, and prognostication including prediction of intensive care unit admissions for patients with myasthenia gravis. Despite these remarkable strides, significant knowledge, attitude, and practice gaps persist, including within the field of electrodiagnostic and neuromuscular medicine. In this narrative review, we highlight the fundamental principles of AI and draw parallels with the intricacies of human brain networks. Specifically, we explore the immense potential that AI holds for applications in electrodiagnostic studies, neuromuscular ultrasound, and other aspects of neuromuscular medicine. While there are exciting possibilities for the future, it is essential to acknowledge and understand the limitations of AI and take proactive steps to mitigate these challenges. This collective endeavor holds immense potential for the advancement of healthcare through the strategic and responsible integration of AI technologies.}, } @article {pmid38149762, year = {2024}, author = {Lopes, CS and Pronto-Laborinho, AC and Conceição, VA and Freitas, T and Matias, GL and Gromicho, M and Santos, NC and de Carvalho, M and Carvalho, FA}, title = {Erythrocytes' surface properties and stiffness predict survival and functional decline in ALS patients.}, journal = {BioFactors (Oxford, England)}, volume = {50}, number = {3}, pages = {558-571}, doi = {10.1002/biof.2030}, pmid = {38149762}, issn = {1872-8081}, support = {COVID/BD/151823/2021//Fundação para a Ciência e a Tecnologia/ ; PD/BD/135045/2017//Fundação para a Ciência e a Tecnologia/ ; PTDC/EMD-TLM/7289/2020//Fundação para a Ciência e a Tecnologia/ ; UID/BIM/50005/2019//Fundação para a Ciência e a Tecnologia/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology/pathology/mortality/blood ; Female ; Middle Aged ; Male ; *Erythrocytes/metabolism/pathology ; *Microscopy, Atomic Force ; Aged ; Surface Properties ; Erythrocyte Membrane/metabolism ; Adult ; Vital Capacity ; Disease Progression ; }, abstract = {Erythrocytes play a fundamental role in oxygen delivery to tissues and binding to inflammatory mediators. Evidences suggest that dysregulated erythrocyte function could contribute to the pathophysiology of several neurodegenerative diseases. We aimed to evaluate changes in morphological, biomechanical, and biophysical properties of erythrocytes from amyotrophic lateral sclerosis (ALS) patients, as new areas of study in this disease. Blood samples were collected from ALS patients, comparing with healthy volunteers. Erythrocytes were assessed using atomic force microscopy (AFM) and zeta potential analysis. The patients' motor and respiratory functions were evaluated using the revised ALS Functional Rating Scale (ALSFRS-R) and percentage of forced vital capacity (%FVC). Patient survival was also assessed. Erythrocyte surface roughness was significantly smoother in ALS patients, and this parameter was a predictor of faster decline in ALSFRS-R scores. ALS patients exhibited higher erythrocyte stiffness, as indicated by reduced AFM tip penetration depth, which predicted a faster ALSFRS-R score and respiratory subscore decay. A lower negative charge on the erythrocyte membrane was predictor of a faster ALSFRS-R and FVC decline. Additionally, a larger erythrocyte surface area was an independent predictor of lower survival. These changes in morphological and biophysical membrane properties of ALS patients' erythrocytes, lead to increased cell stiffness and morphological variations. We speculate that these changes might precipitate motoneurons dysfunction and accelerate disease progression. Further studies should explore the molecular alterations related to these observations. Our findings may contribute to dissect the complex interplay between respiratory function, tissue hypoxia, progression rate, and survival in ALS.}, } @article {pmid38149648, year = {2024}, author = {Nicholas, R and Magliozzi, R and Marastoni, D and Howell, O and Roncaroli, F and Muraro, P and Reynolds, R and Friede, T}, title = {High Levels of Perivascular Inflammation and Active Demyelinating Lesions at Time of Death Associated with Rapidly Progressive Multiple Sclerosis Disease Course: A Retrospective Postmortem Cohort Study.}, journal = {Annals of neurology}, volume = {95}, number = {4}, pages = {706-719}, doi = {10.1002/ana.26870}, pmid = {38149648}, issn = {1531-8249}, mesh = {Humans ; *Multiple Sclerosis/pathology ; Cohort Studies ; Retrospective Studies ; Inflammation/complications ; Brain/pathology ; *Multiple Sclerosis, Chronic Progressive/pathology ; }, abstract = {OBJECTIVE: Analysis of postmortem multiple sclerosis (MS) tissues combined with in vivo disease milestones suggests that whereas perivascular white matter infiltrates are associated with demyelinating activity in the initial stages, leptomeningeal immune cell infiltration, enriched in B cells, and associated cortical lesions contribute to disease progression. We systematically examine the association of inflammatory features and white matter demyelination at postmortem with clinical milestones.

METHODS: In 269 MS brains, 20 sites were examined using immunohistochemistry for active lesions (ALs) and perivenular inflammation (PVI). In a subset of 22, a detailed count of CD20+ B cells and CD3+ T cells in PVIs was performed.

RESULTS: ALs were detected in 22%, whereas high levels of PVI were detected in 52% of cases. ALs were present in 35% of cases with high levels of PVI. Shorter time from onset of progression to death was associated with increased prevalence and higher levels of PVI (both p < 0.0001). Shorter time from onset of progression to wheelchair use was associated with higher prevalence of ALs (odds ratio [OR] = 0.921, 95% confidence interval [CI] = 0.858-0.989, p = 0.0230) and higher level of PVI (OR = 0.932, 95% CI = 0.886-0.981, p = 0.0071). High levels of PVI were associated with meningeal inflammation and increased cortical demyelination and significantly higher levels of B lymphocytes within the PVI.

INTERPRETATION: ALs, a feature of early disease stage, persist up to death in a subgroup with high levels of PVI. These features link to a rapid progressive phase and higher levels of meningeal inflammation and B-cell infiltrates, supporting the hypothesis that chronic inflammation drives progression in MS. ANN NEUROL 2024;95:706-719.}, } @article {pmid38149039, year = {2024}, author = {Ryan, M and Doherty, MA and Al Khleifat, A and Costello, E and Hengeveld, JC and Heverin, M and Al-Chalabi, A and Mclaughlin, RL and Hardiman, O}, title = {C9orf72 Repeat Expansion Discordance in 6 Multigenerational Kindreds.}, journal = {Neurology. Genetics}, volume = {10}, number = {1}, pages = {e200112}, pmid = {38149039}, issn = {2376-7839}, support = {MR/R024804/1/MRC_/Medical Research Council/United Kingdom ; }, abstract = {BACKGROUND AND OBJECTIVES: A hexanucleotide repeat expansion in the noncoding region of the C9orf72 gene is the most common genetically identifiable cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia in populations of European ancestry. Pedigrees associated with this expansion exhibit phenotypic heterogeneity and incomplete disease penetrance, the basis of which is poorly understood. Relatives of those carrying the C9orf72 repeat expansion exhibit a characteristic cognitive endophenotype independent of carrier status. To examine whether additional shared genetic or environmental risks within kindreds could compel this observation, we have conducted a detailed cross-sectional study of the inheritance within multigenerational Irish kindreds carrying the C9orf72 repeat expansion.

METHODS: One hundred thirty-one familial ALS pedigrees, 59 of which carried the C9orf72 repeat expansion (45.0% [95% CI 36.7-53.5]), were identified through the Irish population-based ALS register. C9orf72 genotyping was performed using repeat-primed PCR with amplicon fragment length analysis. Pedigrees were further investigated using SNP, targeted sequencing data, whole-exome sequencing, and whole-genome sequencing.

RESULTS: We identified 21 kindreds where at least 1 family member with ALS carried the C9orf72 repeat expansion and from whom DNA was available from multiple affected family members. Of these, 6 kindreds (28.6% [95% CI 11.8-48.3]) exhibited discordant segregation. The C9orf72 haplotype was studied in 2 families and was found to segregate with the C9orf72-positive affected relative but not the C9orf72-negative affected relative. No other ALS pathogenic variants were identified within these discordant kindreds.

DISCUSSION: Family members of kindreds associated with the C9orf72 repeat expansion may carry an increased risk of developing ALS independent of their observed carrier status. This has implications for assessment and counseling of asymptomatic individuals regarding their genetic risk.}, } @article {pmid38148722, year = {2023}, author = {Kiernan, MC and Halliday, GM and Rowe, DB and Tan, RH}, title = {The importance of patient-centred drug development for amyotrophic lateral sclerosis.}, journal = {Neuropathology and applied neurobiology}, volume = {49}, number = {6}, pages = {e12944}, doi = {10.1111/nan.12944}, pmid = {38148722}, issn = {1365-2990}, support = {//FightMND/ ; //National Health and Medical Research Council./ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy ; *Drug Development ; }, } @article {pmid38148559, year = {2024}, author = {Gautam, S and Latif, S and Kang, YS}, title = {Effect of Various Pathological Conditions on Nitric Oxide Level and L-Citrulline Uptake in Motor Neuron-Like (NSC-34) Cell Lines.}, journal = {Biomolecules & therapeutics}, volume = {32}, number = {1}, pages = {154-161}, pmid = {38148559}, issn = {1976-9148}, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disorder that causes progressive paralysis. L-Citrulline is a non-essential neutral amino acid produced by L-arginine via nitric oxide synthase (NOS). According to previous studies, the pathogenesis of ALS entails glutamate toxicity, oxidative stress, protein misfolding, and neurofilament disruption. In addition, L-citrulline prevents neuronal cell death in brain ischemia; therefore, we investigated the change in the transport of L-citrulline under various pathological conditions in a cell line model of ALS. We examined the uptake of [[14]C]L-citrulline in wild-type (hSOD1wt/WT) and mutant NSC-34/ SOD1[G93A] (MT) cell lines. The cell viability was determined via MTT assay. A transport study was performed to determine the uptake of [[14]C]L-citrulline. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis was performed to determine the expression levels of rat large neutral amino acid transported 1 (rLAT1) in ALS cell lines. Nitric oxide (NO) assay was performed using Griess reagent. L-Citrulline had a restorative effect on glutamate induced cell death, and increased [[14]C]L-citrulline uptake and mRNA levels of the large neutral amino acid transporter (LAT1) in the glutamate-treated ALS disease model (MT). NO levels increased significantly when MT cells were pretreated with glutamate for 24 h and restored by co-treatment with L-citrulline. Co-treatment of MT cells with L-arginine, an NO donor, increased NO levels. NSC-34 cells exposed to high glucose conditions showed a significant increase in [[14]C]L-citrulline uptake and LAT1 mRNA expression levels, which were restored to normal levels upon co-treatment with unlabeled L-citrulline. In contrast, exposure of the MT cell line to tumor necrosis factor alpha, lipopolysaccharides, and hypertonic condition decreased the uptake significantly which was restored to the normal level by co-treating with unlabeled L-citrulline. L-Citrulline can restore NO levels and cellular uptake in ALS-affected cells with glutamate cytotoxicity, pro-inflammatory cytokines, or other pathological states, suggesting that L-citrulline supplementation in ALS may play a key role in providing neuroprotection.}, } @article {pmid38147116, year = {2024}, author = {Louro, H and Vettorazzi, A and López de Cerain, A and Spyropoulou, A and Solhaug, A and Straumfors, A and Behr, AC and Mertens, B and Žegura, B and Fæste, CK and Ndiaye, D and Spilioti, E and Varga, E and Dubreil, E and Borsos, E and Crudo, F and Eriksen, GS and Snapkow, I and Henri, J and Sanders, J and Machera, K and Gaté, L and Le Hegarat, L and Novak, M and Smith, NM and Krapf, S and Hager, S and Fessard, V and Kohl, Y and Silva, MJ and Dirven, H and Dietrich, J and Marko, D}, title = {Hazard characterization of Alternaria toxins to identify data gaps and improve risk assessment for human health.}, journal = {Archives of toxicology}, volume = {98}, number = {2}, pages = {425-469}, pmid = {38147116}, issn = {1432-0738}, support = {101057014//European Commission/ ; }, mesh = {Humans ; *Perylene ; Alternaria/metabolism ; *Mycotoxins/toxicity/analysis ; Mutagens/toxicity/metabolism ; Lactones/toxicity/metabolism ; Risk Assessment ; Food Contamination/analysis ; }, abstract = {Fungi of the genus Alternaria are ubiquitous plant pathogens and saprophytes which are able to grow under varying temperature and moisture conditions as well as on a large range of substrates. A spectrum of structurally diverse secondary metabolites with toxic potential has been identified, but occurrence and relative proportion of the different metabolites in complex mixtures depend on strain, substrate, and growth conditions. This review compiles the available knowledge on hazard identification and characterization of Alternaria toxins. Alternariol (AOH), its monomethylether AME and the perylene quinones altertoxin I (ATX-I), ATX-II, ATX-III, alterperylenol (ALP), and stemphyltoxin III (STTX-III) showed in vitro genotoxic and mutagenic properties. Of all identified Alternaria toxins, the epoxide-bearing analogs ATX-II, ATX-III, and STTX-III show the highest cytotoxic, genotoxic, and mutagenic potential in vitro. Under hormone-sensitive conditions, AOH and AME act as moderate xenoestrogens, but in silico modeling predicts further Alternaria toxins as potential estrogenic factors. Recent studies indicate also an immunosuppressive role of AOH and ATX-II; however, no data are available for the majority of Alternaria toxins. Overall, hazard characterization of Alternaria toxins focused, so far, primarily on the commercially available dibenzo-α-pyrones AOH and AME and tenuazonic acid (TeA). Limited data sets are available for altersetin (ALS), altenuene (ALT), and tentoxin (TEN). The occurrence and toxicological relevance of perylene quinone-based Alternaria toxins still remain to be fully elucidated. We identified data gaps on hazard identification and characterization crucial to improve risk assessment of Alternaria mycotoxins for consumers and occupationally exposed workers.}, } @article {pmid38144173, year = {2023}, author = {Simmatis, LE and Robin, J and Pommée, T and McKinlay, S and Sran, R and Taati, N and Truong, J and Koyani, B and Yunusova, Y}, title = {Validation of automated pipeline for the assessment of a motor speech disorder in amyotrophic lateral sclerosis (ALS).}, journal = {Digital health}, volume = {9}, number = {}, pages = {20552076231219102}, pmid = {38144173}, issn = {2055-2076}, support = {R01 DC013547/DC/NIDCD NIH HHS/United States ; }, abstract = {BACKGROUND AND OBJECTIVE: Amyotrophic lateral sclerosis (ALS) frequently causes speech impairments, which can be valuable early indicators of decline. Automated acoustic assessment of speech in ALS is attractive, and there is a pressing need to validate such tools in line with best practices, including analytical and clinical validation. We hypothesized that data analysis using a novel speech assessment pipeline would correspond strongly to analyses performed using lab-standard practices and that acoustic features from the novel pipeline would correspond to clinical outcomes of interest in ALS.

METHODS: We analyzed data from three standard speech assessment tasks (i.e., vowel phonation, passage reading, and diadochokinesis) in 122 ALS patients. Data were analyzed automatically using a pipeline developed by Winterlight Labs, which yielded 53 acoustic features. First, for analytical validation, data were analyzed using a lab-standard analysis pipeline for comparison. This was followed by univariate analysis (Spearman correlations between individual features in Winterlight and in-lab datasets) and multivariate analysis (sparse canonical correlation analysis (SCCA)). Subsequently, clinical validation was performed. This included univariate analysis (Spearman correlation between automated acoustic features and clinical measures) and multivariate analysis (interpretable autoencoder-based dimensionality reduction).

RESULTS: Analytical validity was demonstrated by substantial univariate correlations (Spearman's ρ > 0.70) between corresponding pairs of features from automated and lab-based datasets, as well as interpretable SCCA feature groups. Clinical validity was supported by strong univariate correlations between automated features and clinical measures (Spearman's ρ > 0.70), as well as associations between multivariate outputs and clinical measures.

CONCLUSION: This novel, automated speech assessment feature set demonstrates substantial promise as a valid tool for analyzing impaired speech in ALS patients and for the further development of these technologies.}, } @article {pmid38143564, year = {2023}, author = {Quillet, R and Gutierrez-Mecinas, M and Polgár, E and Dickie, AC and Boyle, KA and Watanabe, M and Todd, AJ}, title = {Synaptic circuits involving gastrin-releasing peptide receptor-expressing neurons in the dorsal horn of the mouse spinal cord.}, journal = {Frontiers in molecular neuroscience}, volume = {16}, number = {}, pages = {1294994}, pmid = {38143564}, issn = {1662-5099}, support = {/WT_/Wellcome Trust/United Kingdom ; MR/V033638/1/MRC_/Medical Research Council/United Kingdom ; }, abstract = {The superficial dorsal horn (SDH) of the spinal cord contains a diverse array of neurons. The vast majority of these are interneurons, most of which are glutamatergic. These can be assigned to several populations, one of which is defined by expression of gastrin-releasing peptide receptor (GRPR). The GRPR cells are thought to be "tertiary pruritoceptors," conveying itch information to lamina I projection neurons of the anterolateral system (ALS). Surprisingly, we recently found that GRPR-expressing neurons belong to a morphological class known as vertical cells, which are believed to transmit nociceptive information to lamina I ALS cells. Little is currently known about synaptic circuits engaged by the GRPR cells. Here we combine viral-mediated expression of PSD95-tagRFP fusion protein with super-resolution microscopy to reveal sources of excitatory input to GRPR cells. We find that they receive a relatively sparse input from peptidergic and non-peptidergic nociceptors in SDH, and a limited input from A- and C-low threshold mechanoreceptors on their ventral dendrites. They receive synapses from several excitatory interneuron populations, including those defined by expression of substance P, neuropeptide FF, cholecystokinin, neurokinin B, and neurotensin. We investigated downstream targets of GRPR cells by chemogenetically exciting them and identifying Fos-positive (activated) cells. In addition to lamina I projection neurons, many ALS cells in lateral lamina V and the lateral spinal nucleus were Fos-positive, suggesting that GRPR-expressing cells target a broader population of projection neurons than was previously recognised. Our findings indicate that GRPR cells receive a diverse synaptic input from various types of primary afferent and excitatory interneuron, and that they can activate ALS cells in both superficial and deep regions of the dorsal horn.}, } @article {pmid38143551, year = {2023}, author = {Kasindi, A and Carstarphen, KJ}, title = {Bulbar Onset Amyotrophic Lateral Sclerosis in an African American Older Adult.}, journal = {Ochsner journal}, volume = {23}, number = {4}, pages = {353-356}, pmid = {38143551}, issn = {1524-5012}, abstract = {Background: Amyotrophic lateral sclerosis (ALS), a fatal neuromuscular disease, affects the motor tracts and anterior horn cells of the spinal cord, causing both upper and lower motor neuron dysfunction. ALS typically involves progressive peripheral weakness and mobility issues. Case Report: An African American male in his early 70s presented to his primary care provider (PCP) with bulbar weakness and urinary tract symptoms. At presentation, and even later in the disease course, he ambulated well and did not report any limb issues. After some months of worsening symptoms of dyspnea, dysarthria, dysphagia, and urinary incontinence, a diagnosis of ALS was made via collaborative work between the PCP, a medical student, and various medical specialists including a neurosurgeon and neurologist. Because of the absence of limb abnormalities, the patient had difficulty accepting a diagnosis of ALS, thus delaying treatment onset. Conclusion: Clinicians must consider the patient's presentation holistically so that they do not miss insidious, complex, or unique presentations. ALS can present with bulbar symptoms early in the disease course with no upper motor neuron/lower motor neuron involvement. Older adult African American males can present with ALS. Mistrust of health care systems and resistance to science based on religious beliefs can impact patient acceptance of diagnoses and engagement in treatments. Having a long-term relationship with a PCP who also represents the patient's community can influence patient willingness to accept diagnoses, especially those that are life-limiting.}, } @article {pmid38143367, year = {2024}, author = {Gao, J and Leinonen, H and Wang, EJ and Ding, M and Perry, G and Palczewski, K and Wang, X}, title = {Sex-Specific Early Retinal Dysfunction in Mutant TDP-43 Transgenic Mice.}, journal = {Journal of Alzheimer's disease : JAD}, volume = {97}, number = {2}, pages = {927-937}, pmid = {38143367}, issn = {1875-8908}, support = {P30 EY034070/EY/NEI NIH HHS/United States ; R01 EY009339/EY/NEI NIH HHS/United States ; RF1 AG056320/AG/NIA NIH HHS/United States ; RF1 AG065342/AG/NIA NIH HHS/United States ; }, mesh = {Mice ; Humans ; Male ; Female ; Animals ; Mice, Transgenic ; *Amyotrophic Lateral Sclerosis/metabolism ; *Frontotemporal Dementia ; *Neurodegenerative Diseases ; DNA-Binding Proteins/genetics/metabolism ; Retina/pathology ; }, abstract = {BACKGROUND: Increasing evidence has highlighted retinal impairments in neurodegenerative diseases. Dominant mutations in TAR DNA-binding protein 43 (TDP-43) cause amyotrophic lateral sclerosis (ALS), and the accumulation of TDP-43 in the cytoplasm is a pathological hallmark of ALS, frontotemporal dementia (FTD), and many other neurodegenerative diseases.

OBJECTIVE: While homozygous transgenic mice expressing the disease-causing human TDP-43 M337V mutant (TDP-43M337V mice) experience premature death, hemizygous TDP-43M337V mice do not suffer sudden death, but they exhibit age-dependent motor-coordinative and cognitive deficits. This study aims to leverage the hemizygous TDP-43M337V mice as a valuable ALS/FTD disease model for the assessment also of retinal changes during the disease progression.

METHODS: We evaluated the retinal function of young TDP-43M337V mice by full field electroretinogram (ERG) recordings.

RESULTS: At 3-4 months of age, well before the onset of brain dysfunction at 8 months, the ERG responses were notably impaired in the retinas of young female TDP-43M337V mice in contrast to their male counterparts and age-matched non-transgenic mice. Mitochondria have been implicated as critical targets of TDP-43. Further investigation revealed that significant changes in the key regulators of mitochondrial dynamics and bioenergetics were only observed in the retinas of young female TDP-43M337V mice, while these alterations were not present in the brains of either gender.

CONCLUSIONS: Together our findings suggest a sex-specific vulnerability within the retina in the early disease stage, and highlight the importance of retinal changes and mitochondrial markers as potential early diagnostic indicators for ALS, FTD, and other TDP-43 related neurodegenerative conditions.}, } @article {pmid38143357, year = {2024}, author = {de Boer, SCM and Riedl, L and Fenoglio, C and Rue, I and Landin-Romero, R and Matis, S and Chatterton, Z and Galimberti, D and Halliday, G and Diehl-Schmid, J and Piguet, O and Pijnenburg, YAL and Ducharme, S}, title = {Rationale and Design of the "DIagnostic and Prognostic Precision Algorithm for behavioral variant Frontotemporal Dementia" (DIPPA-FTD) Study: A Study Aiming to Distinguish Early Stage Sporadic FTD from Late-Onset Primary Psychiatric Disorders.}, journal = {Journal of Alzheimer's disease : JAD}, volume = {97}, number = {2}, pages = {963-973}, pmid = {38143357}, issn = {1875-8908}, mesh = {Humans ; *Frontotemporal Dementia/genetics ; Prospective Studies ; Prognosis ; Neuropsychological Tests ; Biomarkers ; *Acetamides ; *Isothiocyanates ; }, abstract = {BACKGROUND: The behavioral variant of frontotemporal dementia (bvFTD) is very heterogeneous in pathology, genetics, and disease course. Unlike Alzheimer's disease, reliable biomarkers are lacking and sporadic bvFTD is often misdiagnosed as a primary psychiatric disorder (PPD) due to overlapping clinical features. Current efforts to characterize and improve diagnostics are centered on the minority of genetic cases.

OBJECTIVE: The multi-center study DIPPA-FTD aims to develop diagnostic and prognostic algorithms to help distinguish sporadic bvFTD from late-onset PPD in its earliest stages.

METHODS: The prospective DIPPA-FTD study recruits participants with late-life behavioral changes, suspect for bvFTD or late-onset PPD diagnosis with a negative family history for FTD and/or amyotrophic lateral sclerosis. Subjects are invited to participate after diagnostic screening at participating memory clinics or recruited by referrals from psychiatric departments. At baseline visit, participants undergo neurological and psychiatric examination, questionnaires, neuropsychological tests, and brain imaging. Blood is obtained to investigate biomarkers. Patients are informed about brain donation programs. Follow-up takes place 10-14 months after baseline visit where all examinations are repeated. Results from the DIPPA-FTD study will be integrated in a data-driven approach to develop diagnostic and prognostic models.

CONCLUSIONS: DIPPA-FTD will make an important contribution to early sporadic bvFTD identification. By recruiting subjects with ambiguous or prodromal diagnoses, our research strategy will allow the characterization of early disease stages that are not covered in current sporadic FTD research. Results will hopefully increase the ability to diagnose sporadic bvFTD in the early stage and predict progression rate, which is pivotal for patient stratification and trial design.}, } @article {pmid38142663, year = {2024}, author = {Castro, J and Pedrosa, T and Alves, I and Simão, S and Swash, M and de Carvalho, M}, title = {A neurophysiological approach to mirror movements in amyotrophic lateral sclerosis.}, journal = {Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology}, volume = {158}, number = {}, pages = {27-34}, doi = {10.1016/j.clinph.2023.12.002}, pmid = {38142663}, issn = {1872-8952}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis ; Muscle, Skeletal ; *Movement Disorders ; Neurophysiology ; Transcranial Magnetic Stimulation/methods ; }, abstract = {OBJECTIVE: To investigate mirror activity in amyotrophic lateral sclerosis (ALS) patients, using a simple paradigm of signal quantification.

METHODS: Patients were asked to perform a brief isometric maximum contraction of the abductor digiti minimi (ADM) or tibialis anterior (TA) on one side, while relaxing the contralateral side of the body. Both sides were investigated. Signals were stored and analyzed offline, for quantification of electromyographic signal. Clinical signs of upper motor neuron (UMN) dysfunction, transcranial magnetic stimulation (TMS) for the upper (UL) and lower limbs (LL), the ADM ipsilateral cortical silent period (iSP) and the Edinburgh Cognitive and Behavioral ALS Screen (ECAS) cognitive scale were also investigated.

RESULTS: 42 ALS patients were included. In the 4 investigated muscles the amount of mirror activity was significantly higher than in the matched healthy group. The amount of mirror activity was similar between sides, but significantly higher in UL and LL with abnormal TMS results for ADM (p = 0.005) and TA (p = 0.002), as well as in UL with abnormal iSP values (p = 0.009). No association was found between mirror activity and clinical signs of UMN involvement.

CONCLUSIONS: Mirror activity is a common phenomenon in ALS. Mirror activity intensity corresponds to the severity of UMN dysfunction, as measured by TMS, and probably derives from the abnormal transcallosal inhibition as mirrored by iSP abnormality.

SIGNIFICANCE: Mirror activity is increased in ALS and is associated with abnormal transcallosal inhibition and UMN dysfunction.}, } @article {pmid38141357, year = {2024}, author = {Tang, M and Xiong, M and Zhou, W and Lei, J and Huang, M and Huang, C and Wang, F and Liu, J and Li, J and Xu, X}, title = {Generation of a human induced pluripotent stem cell line (SMUSHi002-A) from an ALS patient carrying a heterozygous mutation c.1562G > A in the FUS gene.}, journal = {Stem cell research}, volume = {74}, number = {}, pages = {103286}, doi = {10.1016/j.scr.2023.103286}, pmid = {38141357}, issn = {1876-7753}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/pathology ; *Induced Pluripotent Stem Cells/metabolism ; *Neurodegenerative Diseases/metabolism ; Motor Neurons/metabolism ; Mutation/genetics ; RNA-Binding Protein FUS/genetics ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease. Affected patients experience gradual loss of their spinal cord and cortical motor neurons with consequent muscle weakness and emaciation, and eventual respiratory failure. The pathogenesis of ALS remains largely unknown although the FUS (sarcoma fusion gene) gene is known to be one of the major pathogenic genes. We have generated an induced pluripotent stem cell line SMUSHi002-A from an ALS patient who carries a heterozygous mutation c.1562G > A in FUS. This cell line will serve as a useful model to investigate disease pathogenesis and develop potential therapeutic approaches for ALS.}, } @article {pmid38141272, year = {2024}, author = {Sancho-Cantus, D and Cubero-Plazas, L and Privado, J and García-Iturrospe, EJA and Cañabate Ros, M and Navarro-Illana, E and Ortí, JER}, title = {Spanish adaptation and validation of the ALS Depression Inventory-12 (ADI-12) in patients with Amyotrophic Lateral Sclerosis.}, journal = {Archives of medical research}, volume = {55}, number = {1}, pages = {102936}, doi = {10.1016/j.arcmed.2023.102936}, pmid = {38141272}, issn = {1873-5487}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/complications/diagnosis/epidemiology ; Depression/diagnosis/etiology/epidemiology ; Surveys and Questionnaires ; Mood Disorders ; Reproducibility of Results ; }, abstract = {BACKGROUND: Patients with Amyotrophic Lateral Sclerosis (ALS) have a higher prevalence of mood disorders, including depression, than the general population. Non-specific measurement instruments have been used to evaluate depression in these patients, which complicates accurate diagnosis. The ALS Depression Inventory (ADI-12) exclusively assesses depressive symptoms in patients with ALS.

AIM: To adapt and validate the ADI-12 in a Spanish sample.

METHODS: A selective design was used with 74 patients with ALS, using the ADI-12 questionnaire. The original instrument was translated and back-translated into Spanish. The internal structure, temporal stability, convergent, and discriminant validity of the instrument were analyzed.

RESULTS: Two confirmatory models showed internal validity (p = 0.502 for the one-factor model, p = 0.507 for the two-factor model). The Cronbach's alpha (0.900 in the first measurement and 0.889 in the second one) indicated a high internal consistency of the test. The Pearson correlation (0.90) indicated high temporal stability. In terms of convergent validity, the ADI-12 showed moderate correlations with the Beck Anxiety Inventory (BAI) (0.51-0.58), and low correlations with time since ALS diagnosis (-0.26 to -0.27).

LIMITATIONS: The main limitation of the present study was the small sample size.

CONCLUSIONS: The ADI-12 is fitted to a single general factor of depression, and the scale shows high internal consistency and high temporal stability, therefore, its use is recommended for the diagnosis of depression in patients with ALS.}, } @article {pmid38141002, year = {2024}, author = {Muhanna, M and Lund, I and Bromberg, M and Wicks, P and Benatar, M and Barnes, B and Pierce, K and Ratner, D and Brown, A and Bertorini, T and Barkhaus, P and Carter, G and Mascias Cadavid, J and McDermott, C and Glass, JD and Pattee, G and Armon, C and Bedlack, R and Li, X}, title = {ALSUntangled #73: Lion's Mane.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {25}, number = {3-4}, pages = {420-423}, doi = {10.1080/21678421.2023.2296557}, pmid = {38141002}, issn = {2167-9223}, mesh = {Animals ; Humans ; *Agaricales ; *Amyotrophic Lateral Sclerosis ; Europe ; *Neurodegenerative Diseases ; }, abstract = {Lion's Mane (Hericium erinaceus) has historically been used as traditional medicine in Asia and Europe for its potential benefits in fighting infection and cancer. It has gained interest in the neurodegenerative disease field because of its mechanisms of action; these include anti-inflammation, neuroprotection, and promoting neurite growth demonstrated in various cell and animal models. A very small, double-blind, placebo-controlled trial in patients with mild cognitive impairment showed a temporary improvement in cognitive function; this finding has yet to be replicated. However, there have been no studies in ALS cell or animal models or in humans with ALS. Lion's Mane appears safe and inexpensive when consumed in powder or capsule, but one anaphylactic case was reported after a patient consumed fresh Lion's Mane mushroom. Currently, we do not have enough information to support the use of Lion's Mane for treating ALS. We support further research in ALS disease models and clinical trials to study its efficacy.}, } @article {pmid38140224, year = {2023}, author = {Park, JS and Ahmad, R and Choe, K and Kang, MH and Park, TJ and Kim, MO}, title = {Immunization Effects of a Novel α-Synuclein-Based Peptide Epitope Vaccine in Parkinson's Disease-Associated Pathology.}, journal = {Vaccines}, volume = {11}, number = {12}, pages = {}, pmid = {38140224}, issn = {2076-393X}, support = {2020M3E5D9080660//National Research Foundation of Korea/ ; }, abstract = {Parkinson's disease (PD) is a chronic neurodegenerative disease that affects the central nervous system, specifically the motor system. It is mainly caused by the loss of dopamine due to the accumulation of α-synuclein (α-syn) protein in the striatum and substantia nigra pars compacta (SNpc). Previous studies have reported that immunization may be a potential preventive strategy for neurodegenerative diseases such as Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS). Therefore, the aim of the study was to design an α-syn specific epitope vaccine and investigate its effect in PD-related pathophysiology using an α-syn-induced mouse model. We used an in silico model to identify and design a non-toxic α-syn-based peptide epitope vaccine and, to overcome poor immunogenicity, the vaccine was coupled with immunogenic carrier proteins, i.e., ovalbumin (OVA) and keyhole limpet haemocyanin (KLH). Our results showed that vaccinated PD mouse models, especially with vaccines with carrier proteins, improved in motor functions compared with the non-vaccinated PD model. Additionally, the vaccinated groups showed increased immunoglobulin G (IgG) levels in the spleen and plasma as well as decreased interleukin-10 (IL-10) levels in the plasma. Furthermore, vaccinated groups, especially OVA and KLH groups, showed decrease in α-syn levels and increased dopamine-related markers, i.e., tyrosine hydroxylase (TH), vesicle monoamine transporter 2 (VMAT2), and dopamine transporter (DAT), and autophagy activities in the striatum and SNpc. Lastly, our data showed decreased neuroinflammation by reducing the activation of microglia and astrocytes and pro-inflammatory cytokines in the immunized groups, especially with OVA and KLH carrier proteins. Overall, these results suggest that vaccination, especially with immunogenic carrier proteins, is effective in reducing the accumulation of α-syn aggregates in the brain and ameliorate PD-related pathophysiology. Hence, further development of this approach might have a potential role in preventing the development of PD.}, } @article {pmid38139294, year = {2023}, author = {Peggion, C and Massimino, ML and Pereira, D and Granuzzo, S and Righetto, F and Bortolotto, R and Agostini, J and Sartori, G and Bertoli, A and Lopreiato, R}, title = {Structural Integrity of Nucleolin Is Required to Suppress TDP-43-Mediated Cytotoxicity in Yeast and Human Cell Models.}, journal = {International journal of molecular sciences}, volume = {24}, number = {24}, pages = {}, pmid = {38139294}, issn = {1422-0067}, support = {DOR2395544/23; BIRD202151/20; DOR2331994/23//University of Padova/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism ; DNA ; *DNA-Binding Proteins/metabolism ; *Frontotemporal Lobar Degeneration/genetics/metabolism ; *Nucleolin/metabolism ; RNA ; Saccharomyces cerevisiae/genetics/metabolism ; }, abstract = {The Transactivating response (TAR) element DNA-binding of 43 kDa (TDP-43) is mainly implicated in the regulation of gene expression, playing multiple roles in RNA metabolism. Pathologically, it is implicated in amyotrophic lateral sclerosis and in a class of neurodegenerative diseases broadly going under the name of frontotemporal lobar degeneration (FTLD). A common hallmark of most forms of such diseases is the presence of TDP-43 insoluble inclusions in the cell cytosol. The molecular mechanisms of TDP-43-related cell toxicity are still unclear, and the contribution to cell damage from either loss of normal TDP-43 function or acquired toxic properties of protein aggregates is yet to be established. Here, we investigate the effects on cell viability of FTLD-related TDP-43 mutations in both yeast and mammalian cell models. Moreover, we focus on nucleolin (NCL) gene, recently identified as a genetic suppressor of TDP-43 toxicity, through a thorough structure/function characterization aimed at understanding the role of NCL domains in rescuing TDP-43-induced cytotoxicity. Using functional and biochemical assays, our data demonstrate that the N-terminus of NCL is necessary, but not sufficient, to exert its antagonizing effects on TDP-43, and further support the relevance of the DNA/RNA binding central region of the protein. Concurrently, data suggest the importance of the NCL nuclear localization for TDP-43 trafficking, possibly related to both TDP-43 physiology and toxicity.}, } @article {pmid38136980, year = {2023}, author = {Bouike, Y and Sakima, M and Taninishi, Y and Matsutani, T and Noguchi, Y and Bo, R and Awano, H and Nishio, H}, title = {Real-Time PCR-Based Screening for Homozygous SMN2 Deletion Using Residual Dried Blood Spots.}, journal = {Genes}, volume = {14}, number = {12}, pages = {}, pmid = {38136980}, issn = {2073-4425}, support = {23K07279//the Ministry of Education, Culture, Sports, Science, and Technology, Japan/ ; }, mesh = {Infant ; Infant, Newborn ; Humans ; Real-Time Polymerase Chain Reaction/methods ; Retrospective Studies ; Prospective Studies ; Gene Deletion ; *Muscular Atrophy, Spinal/diagnosis/genetics ; Motor Neurons ; Neonatal Screening/methods ; Survival of Motor Neuron 2 Protein/genetics ; }, abstract = {The survival motor neuron 2 (SMN2) gene is a recognized modifier gene of spinal muscular atrophy (SMA). However, our knowledge about the role of SMN2-other than its modification of SMA phenotypes-is very limited. Discussions regarding the relationship between homozygous SMN2 deletion and motor neuron diseases, including amyotrophic lateral sclerosis, have been mainly based on retrospective epidemiological studies of the diseases, and the precise relationship remains inconclusive. In the present study, we first estimated that the frequency of homozygous SMN2 deletion was ~1 in 20 in Japan. We then established a real-time polymerase chain reaction (PCR)-based screening method using residual dried blood spots to identify infants with homozygous SMN2 deletion. This method can be applied to a future prospective cohort study to clarify the relationship between homozygous SMN2 deletion and motor neuron diseases. In our real-time PCR experiment, both PCR (low annealing temperatures) and blood (high hematocrit values and low white blood cell counts) conditions were associated with incorrect results (i.e., false negatives and positives). Together, our findings not only help to elucidate the role of SMN2, but also aid in our understanding of the pitfalls of current SMA newborn screening programs for detecting homozygous SMN1 deletions.}, } @article {pmid38136659, year = {2023}, author = {Cilleros-Holgado, P and Gómez-Fernández, D and Piñero-Pérez, R and Romero-Domínguez, JM and Reche-López, D and López-Cabrera, A and Álvarez-Córdoba, M and Munuera-Cabeza, M and Talaverón-Rey, M and Suárez-Carrillo, A and Romero-González, A and Sánchez-Alcázar, JA}, title = {Mitochondrial Quality Control via Mitochondrial Unfolded Protein Response (mtUPR) in Ageing and Neurodegenerative Diseases.}, journal = {Biomolecules}, volume = {13}, number = {12}, pages = {}, pmid = {38136659}, issn = {2218-273X}, support = {FIS PI19/00377 and PI22/00142 grants//Instituto de Salud Carlos III/ ; CTS-5725, PY18-850, and UPO-FEDER 2018 (UPO-1380614)//Regional Government of Andalusia/ ; }, mesh = {Animals ; *Neurodegenerative Diseases/metabolism ; Mitochondria/metabolism ; *Mitochondrial Diseases ; Aging ; Unfolded Protein Response ; }, abstract = {Mitochondria play a key role in cellular functions, including energy production and oxidative stress regulation. For this reason, maintaining mitochondrial homeostasis and proteostasis (homeostasis of the proteome) is essential for cellular health. Therefore, there are different mitochondrial quality control mechanisms, such as mitochondrial biogenesis, mitochondrial dynamics, mitochondrial-derived vesicles (MDVs), mitophagy, or mitochondrial unfolded protein response (mtUPR). The last item is a stress response that occurs when stress is present within mitochondria and, especially, when the accumulation of unfolded and misfolded proteins in the mitochondrial matrix surpasses the folding capacity of the mitochondrion. In response to this, molecular chaperones and proteases as well as the mitochondrial antioxidant system are activated to restore mitochondrial proteostasis and cellular function. In disease contexts, mtUPR modulation holds therapeutic potential by mitigating mitochondrial dysfunction. In particular, in the case of neurodegenerative diseases, such as primary mitochondrial diseases, Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), Amyotrophic Lateral Sclerosis (ALS), or Friedreich's Ataxia (FA), there is a wealth of evidence demonstrating that the modulation of mtUPR helps to reduce neurodegeneration and its associated symptoms in various cellular and animal models. These findings underscore mtUPR's role as a promising therapeutic target in combating these devastating disorders.}, } @article {pmid38136561, year = {2023}, author = {Cotet, C and Alarcan, H and Hérault, O and Corcia, P and Vourc'h, P and Andres, CR and Blasco, H and Veyrat-Durebex, C}, title = {Neutrophil to Lymphocyte Ratio as a Prognostic Marker in Amyotrophic Lateral Sclerosis.}, journal = {Biomolecules}, volume = {13}, number = {12}, pages = {}, pmid = {38136561}, issn = {2218-273X}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis ; Neutrophils ; Retrospective Studies ; Prognosis ; Disease Progression ; Lymphocytes ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is the most common neurodegenerative motor neuron disease and remains misunderstood with a difficult diagnosis and prognosis. The implication of the immune system is recognized in ALS pathophysiology, hence the interest in leucocyte count as lymphocytes and neutrophils. The neutrophil-to-lymphocyte ratio (NLR) has recently been used as a prognosis factor to assess the progression of ALS. Thus, the aim of this study was to analyze the evolution of the NLR during disease evolution in a French cohort of ALS patients and its relation with survival. In this monocentric retrospective study, clinical parameters and NLR were collected in ALS patients followed at the University Hospital of Tours (France). ALS patients were subdivided into three groups regarding their NLR value at inclusion: group 1 (NLR < 2); group 2 (NLR: 2-3); group 3 (NLR > 3). A comparison of qualitative and quantitative clinical and biological variables between NLR groups was performed. Then, Cox regressions were carried out to determine the association of NLR with survival. We observed a significant correlation of NLR with ALSFRS-r score (p < 0.0001) and with vital forced capacity (p = 0.0004) at inclusion. We observed that increased NLR at diagnosis is associated with decreased ALS patients' survival.}, } @article {pmid38135852, year = {2024}, author = {Huang, J and Yu, Y and Pang, D and Li, C and Wei, Q and Cheng, Y and Cui, Y and Ou, R and Shang, H}, title = {Lnc-HIBADH-4 Regulates Autophagy-Lysosome Pathway in Amyotrophic Lateral Sclerosis by Targeting Cathepsin D.}, journal = {Molecular neurobiology}, volume = {61}, number = {7}, pages = {4768-4782}, pmid = {38135852}, issn = {1559-1182}, support = {81871000//National Natural Science Foundation of China/ ; 82101485//National Natural Science Foundation of China/ ; 2022ZYD0051//Sichuan Province Science and Technology Support Program/ ; No.2022NSFSC0750//Sichuan Province Science and Technology Support Program/ ; }, mesh = {Humans ; *Autophagy/physiology ; *Amyotrophic Lateral Sclerosis/genetics/pathology/metabolism ; *RNA, Long Noncoding/genetics/metabolism ; *Lysosomes/metabolism ; *Cathepsin D/metabolism/genetics ; Male ; Female ; Signal Transduction ; MicroRNAs/genetics/metabolism ; Apoptosis/genetics ; Middle Aged ; Cell Proliferation ; Down-Regulation/genetics ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is the most prevalent and lethal class of severe motor neuron diseases (MND) with no efficacious treatment. The pathogenic mechanisms underlying ALS remain unclear. Nearly 90% of patients exhibit sporadic onset (sALS). Therefore, elucidating the pathophysiology of ALS is imperative. Long non-coding RNA (lncRNA) is a large class of non-coding RNAs that regulate transcription, translation, and post-translational processes. LncRNAs contribute to the pathogenesis of diverse neurodegenerative disorders and hold promise as targets for interference in the realm of neurodegeneration. However, the mechanisms of which lncRNAs are involved in ALS have not been thoroughly investigated. We identified and validated a downregulated lncRNA, lnc-HIBADH-4, in ALS which correlated with disease severity and overall survival. Lnc-HIBADH-4 acted as a "molecular sponge" regulating lysosomal function through the lnc-HIBADH-4/miR-326/CTSD pathway, thereby impacting autophagy-lysosome dynamics and the levels of cell proliferation and apoptosis. Therefore, this study discovered and revealed the role of lnc-HIBADH-4 in the pathogenesis of ALS. With further research, lnc-HIBADH-4 is expected to provide a new biomarker in the diagnosis and treatment of ALS.}, } @article {pmid38134913, year = {2024}, author = {Wicke, F and Lorenz, E and Pokora, RM}, title = {[Schätzung der Wirksamkeit der Grippeimpfung anhand von Sekundärdaten: Eine Kohortenstudie und Propensity-Score-Matching-Analyse von Leistungsdaten aus Baden-Württemberg].}, journal = {Gesundheitswesen (Bundesverband der Arzte des Offentlichen Gesundheitsdienstes (Germany))}, volume = {86}, number = {S 03}, pages = {S205-S211}, doi = {10.1055/a-2173-8160}, pmid = {38134913}, issn = {1439-4421}, mesh = {Humans ; Germany/epidemiology ; *Influenza, Human/prevention & control/epidemiology ; *Influenza Vaccines/administration & dosage ; Male ; *Propensity Score ; Female ; Middle Aged ; Adult ; Aged ; Adolescent ; Young Adult ; Cohort Studies ; Aged, 80 and over ; Hospitalization/statistics & numerical data ; Vaccine Efficacy/statistics & numerical data ; Treatment Outcome ; Age Distribution ; Sex Distribution ; Reproducibility of Results ; }, abstract = {Ziel war es die Wirksamkeit der Influenza-Impfung (VE) für die Grippesaison 2014/2015 auf Grundlage von Routinedaten aus Krankenkassendatensatz zu schätzen und zu replizieren. Zusätzlich sollten methodische Aspekte untersucht werden. Es wurden Abrechnungsdaten von 2,64 Millionen Versicherten der AOK Baden-Württemberg mit dortigem Wohnsitz ab 15 Jahren analysiert. Basierend auf Abrechnungsdaten für die Influenza-Impfung 2014, wurden die Teilnehmer als ungeimpft oder geimpft klassifiziert. Kovariablen, die den Zusammenhang zwischen Impfung und Influenzainfektion beeinträchtigen könnten, wurden berücksichtigt. Hierzu gehörten Alter, Geschlecht, Wohnort sowie Kovariablen, die auf den Gesundheitszustand und die Inanspruchnahme von Gesundheitsdienstleistungen hinweisen. Der primäre Endpunkt war ein Krankenhausaufenthalt wegen Influenza während der Grippesaison 2015. Zu den sekundären Endpunkten gehörten unter anderem Krankenhausaufenthalte wegen Lungenentzündung und die Gesamtmortalität. Um eine vergleichbare Gruppe von geimpften und ungeimpften Teilnehmern zu ermitteln, wurde ein Propensity-Score-Matching (PSM) durchgeführt. Es wurde eine Bias-Analyse durchgeführt, bei der die VE vor und nach der Grippesaison geschätzt wurde, also zu Zeitpunkten, in denen angenommen wurde, dass die Influenza nicht in der Bevölkerung zirkulierte und die Impfung nicht wirken konnte. Insgesamt konnten 839.706 Teilnehmer 1:1 gematcht werden. Die geschätzte VE (basierend auf Influenza bedingten Krankenhausaufenthalten) betrug 27% [95%Konfidenzintervall (KI): 17%; 36%], was der Schätzung des RKI für dieselbe Saison (27% [95%KI: -1%; 47%]) entspricht. Die Bias-Analyse zeigte, dass das Ergebnis teilweise durch residuale Konfundierung erklärt werden kann, was zu einer potenziellen Überschätzung des zugrunde liegenden Effekts führt. Die Ergebnisse der sekundären Endpunkte zeigten ähnliche Ergebnisse, obwohl sie wahrscheinlich in höherem Maße durch residuale Konfundierung bedingt sind. Zusammenfassend zeigt sich, dass (1) sekundäre Daten der deutschen Krankenkassen verwendet werden können, um plausible VE-Schätzungen abzuleiten, und dass (2) das PSM eine nützliche und transparente Methode zur Ableitung dieser Schätzungen ist. Darüber hinaus ist (3) residuale Konfundierung ein relevantes Problem in Beobachtungsstudien zu VE und (4) Bias-Analysen vor- und nach der Grippesaison sind eine wesentliche Ergänzung für die Interpretation der Ergebnisse.}, } @article {pmid38134563, year = {2024}, author = {Dave, U and Narain, P and Mishra, D and Gomes, J}, title = {Aggregation of E121K mutant D-amino acid oxidase and ubiquitination-mediated autophagy mechanisms leading to amyotrophic lateral sclerosis.}, journal = {Journal of the neurological sciences}, volume = {456}, number = {}, pages = {122845}, doi = {10.1016/j.jns.2023.122845}, pmid = {38134563}, issn = {1878-5883}, mesh = {Adult ; Humans ; Amino Acids ; *Amyotrophic Lateral Sclerosis/genetics/metabolism ; Autophagy/genetics ; Mutation/genetics ; *Neuroblastoma ; Oxidoreductases ; Protein Aggregates ; Ubiquitin/metabolism ; Ubiquitination ; }, abstract = {Amyotrophic Lateral Sclerosis (ALS) is a terminal adult-onset neuromuscular disorder. Our group has been studying this illness and previously reported novel mutations and rare mutations in a study using next-generation sequencing of DNA samples from Indian ALS patients. In this paper, we focus on the E121K mutation in the DAO gene to understand how it leads to ALS. Our experiments in SH-SY5Y cells indicate that the E121K mutation results in the accumulation of mutant protein aggregates, a change in cell morphology, and the death of neuronal cells. These protein aggregates get ubiquitinated and cause an imbalance in autophagy regulation. We observed an increase in the cellular concentrations of p62, OPTN, and LC3II. Through confocal microscopy studies, we show that the binding of p62 with ubiquitinated aggregates and its recruitment to LC3II mediates autophagosome generation. These relative changes in the key partners in autophagy increase cell death in cells harboring the E121K mutation and is a probable mechanism leading to ALS.}, } @article {pmid38132330, year = {2023}, author = {Spisni, E and Valerii, MC and Massimino, ML}, title = {Essential Oil Molecules Can Break the Loop of Oxidative Stress in Neurodegenerative Diseases.}, journal = {Biology}, volume = {12}, number = {12}, pages = {}, pmid = {38132330}, issn = {2079-7737}, support = {0000//Xeda international (1397 Route Nationale 7, Zac la Crau, 13670 Saint Andiol, France)./ ; }, abstract = {Essential oils (EOs) are mixtures of volatile compounds, extracted from aromatic plants, with multiple activities including antioxidant and anti-inflammatory ones. EOs are complex mixtures easy to find on the market and with low costs. In this mini narrative review, we have collected the results of in vitro and in vivo studies, which tested these EOs on validated models of neurodegeneration and in particular of the two main neurodegenerative diseases (NDs) that afflict humans: Alzheimer's and Parkinson's. Since EO compositions can vary greatly, depending on the environmental conditions, plant cultivar, and extraction methods, we focused our attention to studies involving single EO molecules, and in particular those that have demonstrated the ability to cross the blood-brain barrier. These single EO molecules, alone or in defined mixtures, could be interesting new therapies to prevent or slow down oxidative and inflammatory processes which are common mechanisms that contribute to neuronal death in all NDs.}, } @article {pmid38132101, year = {2023}, author = {Liu, T and Wetzel, L and Zhu, Z and Kumaraguru, P and Gorthi, V and Yan, Y and Bukhari, MZ and Ermekbaeva, A and Jeon, H and Kee, TR and Woo, JA and Kang, DE}, title = {Disruption of Mitophagy Flux through the PARL-PINK1 Pathway by CHCHD10 Mutations or CHCHD10 Depletion.}, journal = {Cells}, volume = {12}, number = {24}, pages = {}, pmid = {38132101}, issn = {2073-4409}, support = {I01 BX004680/BX/BLRD VA/United States ; R21 AG070299/AG/NIA NIH HHS/United States ; R01 AG080924/AG/NIA NIH HHS/United States ; R01AG080924/NH/NIH HHS/United States ; R21 AG077735/AG/NIA NIH HHS/United States ; R01NS122350/NH/NIH HHS/United States ; R21AG070299/NH/NIH HHS/United States ; R01 AG059721/AG/NIA NIH HHS/United States ; R01AG059721/NH/NIH HHS/United States ; R01 NS122350/NS/NINDS NIH HHS/United States ; P30 AG072959/AG/NIA NIH HHS/United States ; RF1AG053060/NH/NIH HHS/United States ; RF1 AG053060/AG/NIA NIH HHS/United States ; R01AG067741/NH/NIH HHS/United States ; RF1 NS122218/NS/NINDS NIH HHS/United States ; R01 AG067741/AG/NIA NIH HHS/United States ; }, mesh = {Animals ; Humans ; *Amyotrophic Lateral Sclerosis/metabolism ; *Frontotemporal Dementia/genetics/pathology ; Mitophagy/genetics ; Mitochondrial Proteins/genetics/metabolism ; Mutation/genetics ; DNA-Binding Proteins/genetics/metabolism ; Protein Kinases/genetics ; Mammals/metabolism ; Metalloproteases/genetics ; }, abstract = {Coiled-coil-helix-coiled-coil-helix domain-containing 10 (CHCHD10) is a nuclear-encoded mitochondrial protein which is primarily mutated in the spectrum of familial and sporadic amyotrophic lateral sclerosis (ALS)-frontotemporal dementia (FTD). Endogenous CHCHD10 levels decline in the brains of ALS-FTD patients, and the CHCHD10[S59L] mutation in Drosophila induces dominant toxicity together with PTEN-induced kinase 1 (PINK1), a protein critical for the induction of mitophagy. However, whether and how CHCHD10 variants regulate mitophagy flux in the mammalian brain is unknown. Here, we demonstrate through in vivo and in vitro models, as well as human FTD brain tissue, that ALS/FTD-linked CHCHD10 mutations (R15L and S59L) impair mitophagy flux and mitochondrial Parkin recruitment, whereas wild-type CHCHD10 (CHCHD10[WT]) normally enhances these measures. Specifically, we show that CHCHD10[R15L] and CHCHD10[S59L] mutations reduce PINK1 levels by increasing PARL activity, whereas CHCHD10[WT] produces the opposite results through its stronger interaction with PARL, suppressing its activity. Importantly, we also demonstrate that FTD brains with TAR DNA-binding protein-43 (TDP-43) pathology demonstrate disruption of the PARL-PINK1 pathway and that experimentally impairing mitophagy promotes TDP-43 aggregation. Thus, we provide herein new insights into the regulation of mitophagy and TDP-43 aggregation in the mammalian brain through the CHCHD10-PARL-PINK1 pathway.}, } @article {pmid38131803, year = {2023}, author = {Miteva, D and Vasilev, GV and Velikova, T}, title = {Role of Specific Autoantibodies in Neurodegenerative Diseases: Pathogenic Antibodies or Promising Biomarkers for Diagnosis.}, journal = {Antibodies (Basel, Switzerland)}, volume = {12}, number = {4}, pages = {}, pmid = {38131803}, issn = {2073-4468}, support = {BG-RRP-2.004-0008//the European Union-NextGenerationEU, through the National Recovery and Resilience Plan of the Republic of Bulgaria/ ; }, abstract = {Neurodegenerative diseases (NDDs) affect millions of people worldwide. They develop due to the pathological accumulation and aggregation of various misfolded proteins, axonal and synaptic loss and dysfunction, inflammation, cytoskeletal abnormalities, defects in DNA and RNA, and neuronal death. This leads to the activation of immune responses and the release of the antibodies against them. Recently, it has become clear that autoantibodies (Aabs) can contribute to demyelination, axonal loss, and brain and cognitive dysfunction. This has significantly changed the understanding of the participation of humoral autoimmunity in neurodegenerative disorders. It is crucial to understand how neuroinflammation is involved in neurodegeneration, to aid in improving the diagnostic and therapeutic value of Aabs in the future. This review aims to provide data on the immune system's role in NDDs, the pathogenic role of some specific Aabs against molecules associated with the most common NDDs, and their potential role as biomarkers for monitoring and diagnosing NDDs. It is suggested that the autoimmune aspects of NDDs will facilitate early diagnosis and help to elucidate previously unknown aspects of the pathobiology of these diseases.}, } @article {pmid38131496, year = {2023}, author = {Lynch, HF}, title = {Big Mistake: Knowing and Doing Better in Patient Engagement.}, journal = {The Hastings Center report}, volume = {53}, number = {6}, pages = {2}, doi = {10.1002/hast.1537}, pmid = {38131496}, issn = {1552-146X}, mesh = {Humans ; Female ; Patient Participation ; *Bioethics ; Ethicists ; Dissent and Disputes ; *Amyotrophic Lateral Sclerosis/therapy ; }, abstract = {Pushing back on policies favored by dying patients is a challenging endeavor, requiring tact, engagement, openness to bidirectional learning, and willingness to offer alternative solutions. It's easy to make missteps, especially in the age of social media. Holly Fernandez Lynch shares her experience learning with and from the amyotrophic lateral sclerosis (ALS) community, first as a caricature of an ivory tower bioethicist and more recently as a trusted advisor, at least for some. Patient-engaged bioethics doesn't mean taking the view that patients are always right, but even when disagreement continues, progress is possible if academics and patients recognize the unique expertise each has to offer.}, } @article {pmid38129934, year = {2023}, author = {Marriott, H and Kabiljo, R and Hunt, GP and Khleifat, AA and Jones, A and Troakes, C and , and , and Pfaff, AL and Quinn, JP and Koks, S and Dobson, RJ and Schwab, P and Al-Chalabi, A and Iacoangeli, A}, title = {Unsupervised machine learning identifies distinct ALS molecular subtypes in post-mortem motor cortex and blood expression data.}, journal = {Acta neuropathologica communications}, volume = {11}, number = {1}, pages = {208}, pmid = {38129934}, issn = {2051-5960}, support = {MR/R024804/1/MRC_/Medical Research Council/United Kingdom ; Motor Neurone Disease Association/MNDA_/Motor Neurone Disease Association/United Kingdom ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/pathology ; Unsupervised Machine Learning ; *Motor Cortex/metabolism ; Brain/pathology ; Autopsy ; }, abstract = {Amyotrophic lateral sclerosis (ALS) displays considerable clinical and genetic heterogeneity. Machine learning approaches have previously been utilised for patient stratification in ALS as they can disentangle complex disease landscapes. However, lack of independent validation in different populations and tissue samples have greatly limited their use in clinical and research settings. We overcame these issues by performing hierarchical clustering on the 5000 most variably expressed autosomal genes from motor cortex expression data of people with sporadic ALS from the KCL BrainBank (N = 112). Three molecular phenotypes linked to ALS pathogenesis were identified: synaptic and neuropeptide signalling, oxidative stress and apoptosis, and neuroinflammation. Cluster validation was achieved by applying linear discriminant analysis models to cases from TargetALS US motor cortex (N = 93), as well as Italian (N = 15) and Dutch (N = 397) blood expression datasets, for which there was a high assignment probability (80-90%) for each molecular subtype. The ALS and motor cortex specificity of the expression signatures were tested by mapping KCL BrainBank controls (N = 59), and occipital cortex (N = 45) and cerebellum (N = 123) samples from TargetALS to each cluster, before constructing case-control and motor cortex-region logistic regression classifiers. We found that the signatures were not only able to distinguish people with ALS from controls (AUC 0.88 ± 0.10), but also reflect the motor cortex-based disease process, as there was perfect discrimination between motor cortex and the other brain regions. Cell types known to be involved in the biological processes of each molecular phenotype were found in higher proportions, reinforcing their biological interpretation. Phenotype analysis revealed distinct cluster-related outcomes in both motor cortex datasets, relating to disease onset and progression-related measures. Our results support the hypothesis that different mechanisms underpin ALS pathogenesis in subgroups of patients and demonstrate potential for the development of personalised treatment approaches. Our method is available for the scientific and clinical community at https://alsgeclustering.er.kcl.ac.uk .}, } @article {pmid38129650, year = {2023}, author = {Ito, H and Machida, K and Hasumi, M and Ueyama, M and Nagai, Y and Imataka, H and Taguchi, H}, title = {Reconstitution of C9orf72 GGGGCC repeat-associated non-AUG translation with purified human translation factors.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {22826}, pmid = {38129650}, issn = {2045-2322}, support = {JPMJFS2112//Japan Science and Technology Agency/ ; JP26116002//Ministry of Education, Culture, Sports, Science and Technology/ ; JP18H03984//Ministry of Education, Culture, Sports, Science and Technology/ ; JP21H04763//Ministry of Education, Culture, Sports, Science and Technology/ ; JP20H05925//Ministry of Education, Culture, Sports, Science and Technology/ ; 2019-25//Mitsubishi Foundation/ ; 2019//Uehara Memorial Foundation/ ; }, mesh = {Peptide Chain Elongation, Translational ; Peptide Elongation Factors/metabolism ; Humans ; *C9orf72 Protein/genetics ; Frameshifting, Ribosomal ; Peptide Chain Initiation, Translational ; In Vitro Techniques ; HeLa Cells ; *Protein Biosynthesis ; Amyotrophic Lateral Sclerosis/genetics ; Frontotemporal Dementia/genetics ; }, abstract = {Nucleotide repeat expansion of GGGGCC (G4C2) in the non-coding region of C9orf72 is the most common genetic cause underlying amyotrophic lateral sclerosis and frontotemporal dementia. Transcripts harboring this repeat expansion undergo the translation of dipeptide repeats via a non-canonical process known as repeat-associated non-AUG (RAN) translation. In order to ascertain the essential components required for RAN translation, we successfully recapitulated G4C2-RAN translation using an in vitro reconstituted translation system comprising human factors, namely the human PURE system. Our findings conclusively demonstrate that the presence of fundamental translation factors is sufficient to mediate the elongation from the G4C2 repeat. Furthermore, the initiation mechanism proceeded in a 5' cap-dependent manner, independent of eIF2A or eIF2D. In contrast to cell lysate-mediated RAN translation, where longer G4C2 repeats enhanced translation, we discovered that the expansion of the G4C2 repeats inhibited translation elongation using the human PURE system. These results suggest that the repeat RNA itself functions as a repressor of RAN translation. Taken together, our utilization of a reconstituted RAN translation system employing minimal factors represents a distinctive and potent approach for elucidating the intricacies underlying RAN translation mechanism.}, } @article {pmid38129120, year = {2024}, author = {Allison, RL and Ebert, AD}, title = {ALS iPSC-derived microglia and motor neurons respond to astrocyte-targeted IL-10 and CCL2 modulation.}, journal = {Human molecular genetics}, volume = {33}, number = {6}, pages = {530-542}, doi = {10.1093/hmg/ddad209}, pmid = {38129120}, issn = {1460-2083}, support = {//Medical College of Wisconsin Center for Immunology/ ; //Neuroscience Research Center/ ; }, mesh = {Humans ; Interleukin-10/genetics ; Astrocytes ; C9orf72 Protein ; Microglia ; *Amyotrophic Lateral Sclerosis/genetics ; *Induced Pluripotent Stem Cells ; *Neurodegenerative Diseases ; Superoxide Dismutase-1/genetics ; Motor Neurons ; Chemokine CCL2/genetics ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the loss of upper and lower motor neurons (MNs). The loss of MNs in ALS leads to muscle weakness and wasting, respiratory failure, and death often within two years of diagnosis. Glial cells in ALS show aberrant expression of pro-inflammatory and neurotoxic proteins associated with activation and have been proposed as ideal therapeutic targets. In this study, we examined astrocyte-targeted treatments to reduce glial activation and neuron pathology using cells differentiated from ALS patient-derived iPSC carrying SOD1 and C9ORF72 mutations. Specifically, we tested the ability of increasing interleukin 10 (IL-10) and reducing C-C motif chemokine ligand 2 (CCL2/MCP-1) signaling targeted to astrocytes to reduce activation phenotypes in both astrocytes and microglia. Overall, we found IL10/CCL2NAb treated astrocytes to support anti-inflammatory phenotypes and reduce neurotoxicity, through different mechanisms in SOD1 and C9ORF72 cultures. We also found altered responses of microglia and motor neurons to astrocytic influences when cells were cultured together rather than in isolation. Together these data support IL-10 and CCL2 as non-mutation-specific therapeutic targets for ALS and highlight the role of glial-mediated pathology in this disease.}, } @article {pmid38128275, year = {2024}, author = {Alcaraz, MR and Espinosa-Mansilla, A and Durán-Merás, I and Muñoz de la Peña, A}, title = {An optimized methodology for the determination of multiclass organic ultraviolet sunscreens and metabolites in human milk through chromatographic and chemometric resolution.}, journal = {Talanta}, volume = {270}, number = {}, pages = {125560}, doi = {10.1016/j.talanta.2023.125560}, pmid = {38128275}, issn = {1873-3573}, mesh = {Humans ; *Milk, Human ; Sunscreening Agents ; Chemometrics ; Ecosystem ; Chromatography, Reverse-Phase ; *Liquid Phase Microextraction/methods ; Chromatography, High Pressure Liquid/methods ; }, abstract = {Organic UV filters (UVFS) are used to mitigate the dermal effects associated with health risks from UV radiation, making them essential in personal care products. UVFS are frequently identified in environmental samples due to their high lipophilicity and persistence, underscoring the urgency of comprehensive assessments and regulatory measures aimed at safeguarding ecosystems and human health. The present study reports a multiclass analytical method for determining 16 UV sunscreens and metabolites in breast milk based on an ultrasound-assisted-dispersive liquid-liquid micro-extraction (UA-DLLME) with further chromatographic and chemometric resolution. The experimental conditions of the UA-DLLME were optimized through the implementation of the Design of Experiment tools. To model the responses, least-squares and artificial neural network methodologies were implemented. The optimal conditions were found by employing the desirability function. The samples were analyzed through reverse-phase liquid chromatographic separation, UV diode array, and fast-scanning fluorescence detection. The chromatographic analysis enabled the resolution of 16 analytes in a total time of 13.0 min. Multivariate curve resolution-alternating least-square (MCR-ALS) modelling was implemented to resolve analytes that were not fully resolved and to determine analytes that coeluted with endogenous components of the breast milk samples. An enrichment factor of 5-fold concentration was obtained with this methodology, reaching recoveries between 65 % and 105 % for 13 multiclass UV sunscreens and metabolites in breast milk samples with RSD % and REP % lower than 12 %.}, } @article {pmid38128171, year = {2024}, author = {Manrique Rabelo, CM}, title = {[Resistance to the use of a wheelchair and gait aids by patients with amyotrophic ALS: Learned beliefs and attitudes].}, journal = {Rehabilitacion}, volume = {58}, number = {1}, pages = {100830}, doi = {10.1016/j.rh.2023.100830}, pmid = {38128171}, issn = {1578-3278}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/complications ; Gait ; *Wheelchairs ; Muscular Atrophy ; }, } @article {pmid38127306, year = {2023}, author = {Ho, DT and Berry, JD}, title = {The Intense Psychological Burden of ALS, the Enduring Strength of People Living With ALS, and the Tools We Can Use to Help.}, journal = {The Journal of clinical psychiatry}, volume = {85}, number = {1}, pages = {}, doi = {10.4088/JCP.23com15173}, pmid = {38127306}, issn = {1555-2101}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/psychology ; }, } @article {pmid38127305, year = {2023}, author = {Lester, EG and Vitolo, OV and Flaherty, A and Beaussant, Y and Cramer, M and Harley, R and Cohen, JN}, title = {"When Will All of This End?": A 65-Year-Old Man With Amyotrophic Lateral Sclerosis and Psychiatric Distress.}, journal = {The Journal of clinical psychiatry}, volume = {85}, number = {1}, pages = {}, doi = {10.4088/JCP.23ct15038}, pmid = {38127305}, issn = {1555-2101}, mesh = {Aged ; Humans ; Male ; *Amyotrophic Lateral Sclerosis/complications/diagnosis/therapy ; *Cognitive Behavioral Therapy ; Psychotherapy ; *Psychological Distress ; }, abstract = {Patients with amyotrophic lateral sclerosis (ALS) are impacted both physically and psychiatrically during their illness. Emotional distress (ie, anxiety, depression, stress) is common in patients diagnosed with ALS, as prognosis is poor and there are very few effective treatments. The progression of symptoms is unpredictable, and all cases are terminal. Neuropsychiatric symptoms are also increasingly recognized as part of ALS symptomatology. There are currently no empirically supported interventions or best practices for adjustment to ALS. This case presents both the psychological and pharmacologic aspects of caring for a patient with ALS. Psychotherapy utilized a cognitive behavioral therapy-informed approach, and pharmacotherapy was tailored to the specific needs of the patient. We explore how these approaches impacted our patient, as well as how ALS-specific challenges presented throughout the course of treatment.}, } @article {pmid38127186, year = {2024}, author = {Guo, R and Chen, Y and Zhang, J and Zhou, Z and Feng, B and Du, X and Liu, X and Ma, J and Cui, H}, title = {Neural Differentiation and spinal cord organoid generation from induced pluripotent stem cells (iPSCs) for ALS modelling and inflammatory screening.}, journal = {Molecular neurobiology}, volume = {61}, number = {7}, pages = {4732-4749}, pmid = {38127186}, issn = {1559-1182}, support = {81801278//Natural Science Foundation of China/ ; 201608130015//China National Textile and Apparel Council/ ; H2019206637//Natural Science Foundation of Hebei Province/ ; H2015206409//Natural Science Foundation of Hebei Province/ ; H2020206557//Key Natural Science Foundation of Hebei Province/ ; C20190509//Overseas researcher Program in Hebei Provincial Department of human resources and social security/ ; }, mesh = {*Induced Pluripotent Stem Cells/metabolism ; Humans ; *Amyotrophic Lateral Sclerosis/pathology/genetics/metabolism ; *Organoids/metabolism/pathology ; *Cell Differentiation ; *Spinal Cord/pathology ; *Motor Neurons/pathology/metabolism ; Astrocytes/metabolism/pathology ; Inflammation/pathology ; C9orf72 Protein/genetics/metabolism ; Models, Biological ; Neurons/metabolism/pathology ; }, abstract = {C9orf72 genetic mutation is the most common genetic cause of ALS/FTD accompanied by abnormal protein insufficiency. Induced pluripotent stem cell (iPSC)-derived two-dimensional (2D) and three-dimensional (3D) cultures are providing new approaches. Therefore, this study established neuronal cell types and generated spinal cord organoids (SCOs) derived from C9orf72 knockdown human iPSCs to model ALS disease and screen the unrevealed phenotype. Wild-type (WT) iPSC lines from three healthy donor fibroblasts were established, and pluripotency and differentiation ability were identified by RT-PCR, immunofluorescence and flow cytometry. After infection by the lentivirus with C9orf72-targeting shRNA, stable C9-knockdown iPSC colonies were selected and differentiated into astrocytes, motor neurons and SCOs. Finally, we analyzed the extracted RNA-seq data of human C9 mutant/knockout iPSC-derived motor neurons and astrocytes from the GEO database and the inflammatory regulation-related genes in function and pathways. The expression of inflammatory factors was measured by qRT-PCR. The results showed that both WT-iPSCs and edited C9-iPSCs maintained a similar ability to differentiate into the three germ layers, astrocytes and motor neurons, forming SCOs in a 3D culture system. The constructed C9-SCOs have features of spinal cord development and multiple neuronal cell types, including sensory neurons, motor neurons, and other neurons. Based on the bioinformatics analysis, proinflammatory factors were confirmed to be upregulated in C9-iPSC-derived 2D cells and 3D cultured SCOs. The above differentiated models exhibited low C9orf72 expression and the pathological characteristics of ALS, especially neuroinflammation.}, } @article {pmid38126188, year = {2025}, author = {Alamri, SH and Haque, S and Alghamdi, BS and Tayeb, HO and Azhari, S and Farsi, RM and Elmokadem, A and Alamri, TA and Harakeh, S and Prakash, A and Kumar, V}, title = {Comprehensive mapping of mutations in TDP-43 and α-Synuclein that affect stability and binding.}, journal = {Journal of biomolecular structure & dynamics}, volume = {43}, number = {4}, pages = {1818-1830}, doi = {10.1080/07391102.2023.2293258}, pmid = {38126188}, issn = {1538-0254}, mesh = {*alpha-Synuclein/genetics/chemistry/metabolism ; *DNA-Binding Proteins/genetics/chemistry/metabolism ; Protein Binding ; Humans ; Protein Stability ; Molecular Dynamics Simulation ; *Mutation ; Mutation, Missense ; Binding Sites ; Thermodynamics ; }, abstract = {Abnormal aggregation and amyloid inclusions of TAR DNA-binding protein 43 (TDP-43) and α-Synuclein (α-Syn) are frequently co-observed in amyotrophic lateral sclerosis, Parkinson's disease, and Alzheimer's disease. Several reports showed TDP-43 C-terminal domain (CTD) and α-Syn interact with each other and the aggregates of these two proteins colocalized together in different cellular and animal models. Molecular dynamics simulation was conducted to elucidate the stability of the TDP-43 and Syn complex structure. The interfacial mutations in protein complexes changes the stability and binding affinity of the protein that may cause diseases. Here, we have utilized the computational saturation mutagenesis approach including structure-based stability and binding energy calculations to compute the systemic effects of missense mutations of TDP-43 CTD and α-Syn on protein stability and binding affinity. Most of the interfacial mutations of CTD and α-Syn were found to destabilize the protein and reduced the protein binding affinity. The results thus shed light on the functional consequences of missense mutations observed in TDP-43 associated proteinopathies and may provide the mechanisms of co-morbidities involving these two proteins.Communicated by Ramaswamy H. Sarma.}, } @article {pmid38124685, year = {2024}, author = {Strunge, K and Bostock, H and Howells, J and Cengiz, B and Samusyte, G and Koltzenburg, M and Tankisi, H}, title = {Caffeine and cortical excitability, as measured with paired-pulse transcranial magnetic stimulation.}, journal = {Muscle & nerve}, volume = {69}, number = {2}, pages = {206-212}, doi = {10.1002/mus.28027}, pmid = {38124685}, issn = {1097-4598}, support = {//Lundbeck Foundation/ ; //Grosserer L. F. Foghts Fond/ ; //Aase og Ejnar Danielsens Fond/ ; //Dagmar Marshalls Fond/ ; }, mesh = {Female ; Humans ; Male ; Caffeine/pharmacology ; Chewing Gum ; *Cortical Excitability ; Evoked Potentials, Motor/physiology ; *Motor Cortex/physiology ; Neural Inhibition/physiology ; Transcranial Magnetic Stimulation/methods ; Young Adult ; Adult ; }, abstract = {INTRODUCTION/AIMS: The transcranial magnetic stimulation tests of short-interval intracortical inhibition (SICI) by both conventional amplitude measurements (A-SICI) and threshold-tracking (T-SICI) are important methods to investigate intracortical inhibitory circuits, and T-SICI has been proposed to aid the diagnosis of amyotrophic lateral sclerosis. Beverages containing caffeine are widely consumed, and caffeine has been reported to affect cortical excitability. The aim of this study was to determine whether these SICI tests are affected by caffeine.

METHODS: Twenty-four healthy subjects (13 females, 11 males, aged from 19 to 31, mean: 26.2 ± 2.4 years) were studied in a single fixed-dose randomized double-blind placebo-controlled cross-over trial of 200 mg caffeine or placebo ingested as chewing gum. A-SICI and T-SICI, using parallel tracking (T-SICIp), were performed before and after chewing gum.

RESULTS: There was no significant change in SICI parameters after placebo in A-SICI (p > .10) or T-SICIp (p > .30), and no significant effect of caffeine was found on A-SICI (p > .10) or T-SICIp (p > .50) for any of the interstimulus intervals.

DISCUSSION: There is no need for caffeine abstention before measurements of SICI by either the T-SICI or A-SICI measurements.}, } @article {pmid38123999, year = {2024}, author = {Douglas, AGL and Baralle, D}, title = {Reduced penetrance of gene variants causing amyotrophic lateral sclerosis.}, journal = {Journal of medical genetics}, volume = {61}, number = {3}, pages = {294-297}, doi = {10.1136/jmg-2023-109580}, pmid = {38123999}, issn = {1468-6244}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/epidemiology/genetics/pathology ; *Frontotemporal Dementia/epidemiology/genetics ; C9orf72 Protein/genetics ; Penetrance ; Superoxide Dismutase-1/genetics ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis overlaps aetiologically and genetically with frontotemporal dementia and occurs in both familial and apparently sporadic forms. The most commonly implicated genes are C9orf72, SOD1, TARDBP and FUS. Penetrance of disease-causing variants in these genes is known to be incomplete, but has not been well studied at population level.

OBJECTIVE: We sought to determine the population-level penetrance of pathogenic and likely pathogenic variants in genes commonly causing amyotrophic lateral sclerosis.

METHODS: Published epidemiological data for amyotrophic lateral sclerosis and frontotemporal dementia were used to calculate expected frequencies of disease-causing variants per gene at population level. Variant data from gnomAD and ClinVar databases were used to ascertain observed numbers of disease-causing variants and to estimate population-level penetrance per gene. Data for C9orf72 were obtained from the published literature.

RESULTS: Maximum population penetrance for either amyotrophic lateral sclerosis or frontotemporal dementia was found to be 33% for C9orf72 (95% CI (20.9 to 53.2)), 54% for SOD1 (95% CI (32.7 to 88.6)), 38% for TARDBP (95% CI (21.1 to 69.8)) and 19% for FUS (95% CI (13.0 to 28.4)).

CONCLUSION: Population-level penetrance of amyotrophic lateral sclerosis disease genes is reduced. This finding has implications for the genetic testing and counselling of affected individuals and their unaffected relatives.}, } @article {pmid38123494, year = {2024}, author = {Nolano, M and Provitera, V and Caporaso, G and Fasolino, I and Borreca, I and Stancanelli, A and Iuzzolino, VV and Senerchia, G and Vitale, F and Tozza, S and Ruggiero, L and Iodice, R and Ferrari, S and Santoro, L and Manganelli, F and Dubbioso, R}, title = {Skin innervation across amyotrophic lateral sclerosis clinical stages: new prognostic biomarkers.}, journal = {Brain : a journal of neurology}, volume = {147}, number = {5}, pages = {1740-1750}, doi = {10.1093/brain/awad426}, pmid = {38123494}, issn = {1460-2156}, support = {//Istituti Clinici Scientifici Maugeri IRCCS/ ; //Italian Ministry of Health/ ; //Ministry of University and Research/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/pathology ; Male ; Female ; Middle Aged ; *Skin/innervation/pathology ; Aged ; Prognosis ; Biomarkers/blood ; Neural Conduction/physiology ; Adult ; Disease Progression ; Neurofilament Proteins/blood/metabolism ; Longitudinal Studies ; }, abstract = {Over recent decades, peripheral sensory abnormalities, including the evidence of cutaneous denervation, have been reported among the non-motor manifestations in amyotrophic lateral sclerosis (ALS). However, a correlation between cutaneous innervation and clinical features has not been found. The aims of this study were to assess sensory involvement by applying a morpho-functional approach to a large population of ALS patients stratified according to King's stages and correlate these findings with the severity and prognosis of the disease. We recruited 149 ALS patients and 41 healthy controls. Patients undertook clinical questionnaires for small fibre neuropathy symptoms (Small Fiber Neuropathy Symptoms Inventory Questionnaire) and underwent nerve conductions studies (NCS) and 3-mm punch skin biopsies from leg, thigh and fingertip. We assessed intraepidermal nerve fibre (IENF) and Meissner corpuscle (MC) density by applying an indirect immunofluorescence technique. Moreover, a subset of 65 ALS patients underwent a longitudinal study with repeat biopsies from the thigh at 6- and 12-month follow-ups. Serum NfL levels were measured in 40 patients. Sensory symptoms and sensory NCS abnormalities were present in 32.2% and 24% of patients, respectively, and increased across clinical stages. Analogously, we observed a progressive reduction in amplitude of the sensory and motor ulnar nerve potential from stage 1 to stage 4. Skin biopsy showed a significant loss of IENFs and MCs in ALS compared with healthy controls (all P < 0.001). Across the clinical stages, we found a progressive reduction in MCs (P = 0.004) and an increase in IENFs (all P < 0.027). The increase in IENFs was confirmed by the longitudinal study. Interestingly, the MC density inversely correlated with NfL level (r = -0.424, P = 0.012), and survival analysis revealed that low MC density, higher NfL levels and increasing IENF density over time were associated with a poorer prognosis (all P < 0.024). To summarize, in patients with ALS, peripheral sensory involvement worsens in parallel with motor disability. Furthermore, the correlation between skin innervation and disease activity may suggest the use of skin innervation as a putative prognostic biomarker.}, } @article {pmid38123099, year = {2024}, author = {Stackhouse, LA and Coops, NC and Kuiper, SD and Hinch, SG and White, JC and Tompalski, P and Nonis, A and Gergel, SE}, title = {Modeling instream temperature from solar insolation under varying timber harvesting intensities using RPAS laser scanning.}, journal = {The Science of the total environment}, volume = {912}, number = {}, pages = {169459}, doi = {10.1016/j.scitotenv.2023.169459}, pmid = {38123099}, issn = {1879-1026}, abstract = {Stream temperatures are influenced by the amount of solar insolation they receive. Increasing stream temperatures associated with climate warming pose detrimental health risks to freshwater ecosystems. In British Columbia (BC), Canada, timber harvesting along forested streams is managed using riparian buffer zones of varying widths and designations. Within buffer zones, depending on distance from the stream, selective thinning may be permitted or harvest may be forbidden. In this study, we used airborne laser scanning (ALS) point cloud data acquired via a remotely piloted aircraft system (RPAS) to derive forest canopy characteristics that were then used to estimate daily incoming summer and fall solar insolation for five stream reaches in coastal conifer-dominated temperate forests in Vancouver Island, BC, Canada. We then examined empirical relationships between estimated insolation and actual instream temperature measurements. Based on these empirical relationships, the potential effects of timber harvest on instream temperatures were simulated by comparing scenarios of different riparian forest harvest intensities. Our results indicated that modeled solar insolation explained 43-90 % of the variation in observed stream reach temperatures, and furthermore, when a single cold-water stream reach was excluded explained an overall 81 % of variation. Simulated harvesting scenarios generally projected increases in maximum stream reach temperatures 1-2 °C in summer and early fall months. However, in a full clearcut scenario (i.e. where all trees were removed), maximum stream reach temperatures increased as much as 5.8 °C. Our results emphasize the importance of retaining riparian vegetation for the maintenance of habitable temperatures for freshwater-reliant fish with thermal restrictions. In addition, we demonstrate the feasibility of RPAS-based monitoring of stream reach shading and canopy cover, enabling detailed assessment of environmental stressors faced by fish populations under climate warming.}, } @article {pmid38117120, year = {2024}, author = {Vaage, AM and Benth, JŠ and Meyer, HE and Holmøy, T and Nakken, O}, title = {Premorbid lipid levels and long-term risk of ALS-a population-based cohort study.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {25}, number = {3-4}, pages = {358-366}, doi = {10.1080/21678421.2023.2295455}, pmid = {38117120}, issn = {2167-9223}, mesh = {Female ; Humans ; Male ; Cholesterol, LDL ; Cohort Studies ; *Amyotrophic Lateral Sclerosis/diagnosis/epidemiology ; Triglycerides ; Cholesterol, HDL ; Risk Factors ; }, abstract = {OBJECTIVE: To assess the temporal relationship between premorbid lipid levels and long-term amyotrophic lateral sclerosis (ALS) risk.

METHODS: From Norwegian cardiovascular health surveys (1974-2003), we collected information on total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), glucose, and other cardiovascular risk factors. ALS incidence and mortality were identified through validated Norwegian health registries. The relation between premorbid lipid levels and ALS risk was assessed by Cox regression models.

RESULTS: Out of 640,066 study participants (51.5% females), 974 individuals (43.5% females) developed ALS. Mean follow-up time was 23.7 (SD 7.1) years among ALS cases. One mmol/l increase in LDL-C was associated with 6% increase in risk for ALS (hazard ratio 1.06 [95% CI: 1.01-1.09]). Higher levels of TC and TG were also associated with increased ALS risk, but only within the last 6-7 years prior to ALS diagnosis or death. No association between HDL-C and ALS risk was found. Adjusting for body mass index, birth cohort, smoking, and physical activity did not alter the results.

CONCLUSIONS: Higher levels of LDL-C are associated with increased ALS risk over 40 years later, compatible with a causal relationship. The temporal relationship between TG, TC, and ALS risk suggests that increased levels of these lipid biomarkers represent consequences of ALS.}, } @article {pmid38116771, year = {2023}, author = {Máčová, L and Kancheva, R and Bičíková, M}, title = {Molecular Regulation of the CNS by Vitamin D.}, journal = {Physiological research}, volume = {72}, number = {S4}, pages = {S339-S356}, doi = {10.33549/physiolres.935248}, pmid = {38116771}, issn = {1802-9973}, mesh = {Humans ; Vitamin D/therapeutic use ; Vitamins ; *Alzheimer Disease ; *Nervous System Diseases ; *Parkinson Disease ; }, abstract = {Vitamin D is a lipid-soluble vitamin that can be found in some foods. It is also produced endogenously (in the presence of ultraviolet light), transported through the blood to the targets organs and this is the reason to consider vitamin D as a hormone. It is known that vitamin D has genomic and non-genomic effects. This review is focused mainly on the vitamin D receptors, the importance of vitamin D as a neuromodulator, the role of vitamin D in the pathophysiology of devastating neurological disorders such as Alzheimer's disease, multiple sclerosis, amyotrophic lateral sclerosis, Parkinson's disease and the benefit of vitamin D and its derivates in alleviating these disorders.}, } @article {pmid38115557, year = {2024}, author = {Nementzik, LR and Thumbadoo, KM and Murray, HC and Gordon, D and Yang, S and Blair, IP and Turner, C and Faull, RLM and Curtis, MA and McLean, C and Nicholson, GA and Swanson, MEV and Scotter, EL}, title = {Distribution of ubiquilin 2 and TDP-43 aggregates throughout the CNS in UBQLN2 p.T487I-linked amyotrophic lateral sclerosis and frontotemporal dementia.}, journal = {Brain pathology (Zurich, Switzerland)}, volume = {34}, number = {3}, pages = {e13230}, pmid = {38115557}, issn = {1750-3639}, support = {//Amelia Pais-Rodriguez and Marcus Gerbich/ ; //Freemasons Foundation of New Zealand/ ; //Health Education Trust/ ; 15-UOA-157//Marsden Fund/ ; //Matteo de Nora/ ; //Motor Neuron Disease NZ/ ; //PaR NZ Golfing/ ; 15-UOA-003//Royal Society Te Apārangi/ ; }, mesh = {Humans ; Adaptor Proteins, Signal Transducing/metabolism ; *Amyotrophic Lateral Sclerosis/pathology ; Autophagy-Related Proteins/metabolism ; DNA-Binding Proteins/metabolism ; *Frontotemporal Dementia/genetics/metabolism ; Mutation ; Transcription Factors/metabolism ; }, abstract = {Mutations in the UBQLN2 gene cause amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The neuropathology of such UBQLN2-linked cases of ALS/FTD is characterised by aggregates of the ubiquilin 2 protein in addition to aggregates of the transactive response DNA-binding protein of 43 kDa (TDP-43). ALS and FTD without UBQLN2 mutations are also characterised by TDP-43 aggregates, that may or may not colocalise with wildtype ubiquilin 2. Despite this, the relative contributions of TDP-43 and ubiquilin 2 to disease pathogenesis remain largely under-characterised, as does their relative deposition as aggregates across the central nervous system (CNS). Here we conducted multiplex immunohistochemistry of three UBQLN2 p.T487I-linked ALS/FTD cases, three non-UBQLN2-linked (sporadic) ALS cases, and 8 non-neurodegenerative disease controls, covering 40 CNS regions. We then quantified ubiquilin 2 aggregates, TDP-43 aggregates and aggregates containing both proteins in regions of interest to determine how UBQLN2-linked and non-UBQLN2-linked proteinopathy differ. We find that ubiquilin 2 aggregates that are negative for TDP-43 are predominantly small and punctate and are abundant in the hippocampal formation, spinal cord, all tested regions of neocortex, medulla and substantia nigra in UBQLN2-linked ALS/FTD but not sporadic ALS. Curiously, the striatum harboured small punctate ubiquilin 2 aggregates in all cases examined, while large diffuse striatal ubiquilin 2 aggregates were specific to UBQLN2-linked ALS/FTD. Overall, ubiquilin 2 is mainly deposited in clinically unaffected regions throughout the CNS such that symptomology in UBQLN2-linked cases maps best to the aggregation of TDP-43.}, } @article {pmid38112783, year = {2024}, author = {Libonati, L and Cambieri, C and Colavito, D and Moret, F and D'Andrea, E and Del Giudice, E and Leon, A and Inghilleri, M and Ceccanti, M}, title = {Genetics screening in an Italian cohort of patients with Amyotrophic Lateral Sclerosis: the importance of early testing and its implication.}, journal = {Journal of neurology}, volume = {271}, number = {4}, pages = {1921-1936}, pmid = {38112783}, issn = {1432-1459}, mesh = {Humans ; Mutation ; *Amyotrophic Lateral Sclerosis/epidemiology ; Superoxide Dismutase-1/genetics ; C9orf72 Protein/genetics ; *Neurodegenerative Diseases ; Italy ; Heat-Shock Proteins/genetics ; Molecular Chaperones/genetics ; }, abstract = {INTRODUCTION: Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease with an elusive etiology. While environmental factors have been considered, familial ALS cases have raised the possibility of genetic involvement. This genetic connection is increasingly evident, even in patients with sporadic ALS. We allowed access to the genetic test to all patients attending our clinic to identify the prevalence and the role of genetic variants in the development of the disease and to identify patients with potentially treatable forms of the disease.

MATERIALS AND METHODS: 194 patients with probable or definite ALS, were enrolled. A comprehensive genetic testing was performed, including sequencing all exons of the SOD1 gene and testing for hexanucleotide intronic repeat expansions (G4C2) in the C9orf72 gene using fluorescent repeat-primed PCR (RP-PCR). Whole Exome NGS Sequencing (WES) was performed, followed by an in silico multigene panel targeting neuromuscular diseases, spastic paraplegia, and motor distal neuropathies. We conducted statistical analyses to compare different patient groups.

RESULTS: Clinically significant pathogenetic variants were detected in 14.43% of cases. The highest prevalence of pathogenetic variants was observed in fALS patients, but a substantial proportion of sALS patients also displayed at least one variant, either pathogenetic or of uncertain significance (VUS). The most observed pathogenetic variant was the expansion of the C9orf72 gene, which was associated with a shorter survival. SOD1 variants were found in 1.6% of fALS and 2.5% of sALS patients.

DISCUSSION: The study reveals a significant number of ALS patients carrying pathogenic or likely pathogenic variants, with a higher prevalence in familial ALS cases. The expansion of the C9orf72 gene emerges as the most common genetic cause of ALS, affecting familial and sporadic cases. Additionally, SOD1 variants are detected at an unexpectedly higher rate, even in patients without a familial history of ALS, underscoring the crucial role of genetic testing in treatment decisions and potential participation in clinical trials. We also investigated variants in genes such as TARDBP, FUS, NEK1, TBK1, and DNAJC7, shedding light on their potential involvement in ALS. These findings underscore the complexity of interpreting variants of uncertain significance (VUS) and their ethical implications in patient communication and genetic counseling for patients' relatives.

CONCLUSION: This study emphasizes the diverse genetic basis of ALS and advocates for integrating comprehensive genetic testing into diagnostic protocols. The evolving landscape of genetic therapies requires identifying all eligible patients transcending traditional familial boundaries. The presence of VUS highlights the multifaceted nature of ALS genetics, prompting further exploration of complex interactions among genetic variants, environmental factors, and disease development.}, } @article {pmid38112636, year = {2024}, author = {Wang, Y and Shen, O and Xu, Q and Sun, L and Jia, Y and Liu, Y and He, Y and Chang, X and Guo, D and Shi, M and Chen, GC and Zheng, J and Zhu, Z}, title = {Genetic analyses identify brain imaging-derived phenotypes associated with the risk of amyotrophic lateral sclerosis.}, journal = {Cerebral cortex (New York, N.Y. : 1991)}, volume = {34}, number = {1}, pages = {}, doi = {10.1093/cercor/bhad496}, pmid = {38112636}, issn = {1460-2199}, support = {82103917//National Natural Science Foundation of China/ ; 21KJB330006//Natural Science Research Project of Jiangsu Provincial Higher Education/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnostic imaging/genetics ; Brain/diagnostic imaging ; Genome-Wide Association Study ; Neuroimaging ; Phenotype ; Polymorphism, Single Nucleotide ; Mendelian Randomization Analysis ; }, abstract = {Brain imaging-derived phenotypes have been suggested to be associated with amyotrophic lateral sclerosis in observational studies, but whether these associations are causal remains unclear. We aimed to assess the potential bidirectional causal associations between imaging-derived phenotypes and amyotrophic lateral sclerosis using bidirectional 2-sample Mendelian randomization analyses. Summary statistics for 469 imaging-derived phenotypes (33,224 individuals) and amyotrophic lateral sclerosis (20,806 cases and 59,804 controls) were obtained from 2 large-scale genome-wide association studies of European ancestry. We used the inverse-variance weighted Mendelian randomization method in the main analysis to assess the bidirectional associations between imaging-derived phenotypes and amyotrophic lateral sclerosis, followed by several sensitivity analyses for robustness validation. In the forward Mendelian randomization analyses, we found that genetically determined high orientation dispersion index in the right cerebral peduncle was associated with the increased risk of amyotrophic lateral sclerosis (odds ratio = 1.30, 95% confidence interval = 1.16-1.45, P = 2.26 × 10-6). In addition, the reverse Mendelian randomization analysis indicated that amyotrophic lateral sclerosis had no effect on 469 imaging-derived phenotypes. Mendelian randomization-Egger regression analysis showed no directional pleiotropy for the association between high orientation dispersion index in the right cerebral peduncle and amyotrophic lateral sclerosis, and sensitivity analyses with different Mendelian randomization models further confirmed these findings. The present systematic bidirectional Mendelian randomization analysis showed that high orientation dispersion index in the right cerebral peduncle might be the potential causal mediator of amyotrophic lateral sclerosis, which may provide predictive guidance for the prevention of amyotrophic lateral sclerosis. Further studies are warranted to replicate our findings and clarify the underlying mechanisms.}, } @article {pmid38112345, year = {2024}, author = {Battaglini, M and Marino, A and Montorsi, M and Carmignani, A and Ceccarelli, MC and Ciofani, G}, title = {Nanomaterials as Microglia Modulators in the Treatment of Central Nervous System Disorders.}, journal = {Advanced healthcare materials}, volume = {13}, number = {12}, pages = {e2304180}, doi = {10.1002/adhm.202304180}, pmid = {38112345}, issn = {2192-2659}, mesh = {*Microglia/drug effects/metabolism ; Humans ; *Nanostructures/chemistry ; Animals ; *Central Nervous System Diseases/drug therapy/metabolism ; Neurodegenerative Diseases/drug therapy/metabolism ; }, abstract = {Microglia play a pivotal role in the central nervous system (CNS) homeostasis, acting as housekeepers and defenders of the surrounding environment. These cells can elicit their functions by shifting into two main phenotypes: pro-inflammatory classical phenotype, M1, and anti-inflammatory alternative phenotype, M2. Despite their pivotal role in CNS homeostasis, microglia phenotypes can influence the development and progression of several CNS disorders such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis, ischemic stroke, traumatic brain injuries, and even brain cancer. It is thus clear that the possibility of modulating microglia activation has gained attention as a therapeutic tool against many CNS pathologies. Nanomaterials are an unprecedented tool for manipulating microglia responses, in particular, to specifically target microglia and elicit an in situ immunomodulation activity. This review focuses the discussion on two main aspects: analyzing the possibility of using nanomaterials to stimulate a pro-inflammatory response of microglia against brain cancer and introducing nanostructures able to foster an anti-inflammatory response for treating neurodegenerative disorders. The final aim is to stimulate the analysis of the development of new microglia nano-immunomodulators, paving the way for innovative and effective therapeutic approaches for the treatment of CNS disorders.}, } @article {pmid38112253, year = {2023}, author = {Juranek, J and Osowski, A and Wojtkiewicz, J and Banach, M}, title = {Plasma levels of soluble RAGE, AGEs and AOPPs at the early stage of amyotrophic lateral sclerosis: A preliminary study.}, journal = {Polimery w medycynie}, volume = {53}, number = {2}, pages = {105-110}, doi = {10.17219/pim/175544}, pmid = {38112253}, issn = {0370-0747}, mesh = {Humans ; Receptor for Advanced Glycation End Products/metabolism ; *Advanced Oxidation Protein Products/metabolism ; *Amyotrophic Lateral Sclerosis ; Longitudinal Studies ; Oxidative Stress ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder with largely unknown pathogenesis and no effective cure. It is believed that several, not mutually exclusive mechanisms contribute to the pathogenesis and progression of this disease, including, among others, elevated oxidative stress, excitotoxicity, increased neuroinflammation, and protein aggregation. Receptor for advanced glycation end products (RAGE) is a part of immunoglobulin superfamily; it is believed to participate in ALS pathogenesis.

OBJECTIVES: Our previous studies on ALS demonstrated that RAGE is likely one of the key players in ALS, acting on its own and in tandem with its oxidative stress and pro-inflammatory ligands, such as advanced glycation end products (AGEs) or advanced oxidation protein products (AOPPs). In this study, based on our previous results, we aimed to establish blood levels of soluble RAGE, AGE and AOPP in ALS patients.

MATERIAL AND METHODS: Forty-six coded and anonymized surplus plasma samples from ALS patients and non-neurological control were used in the study. The plasma levels of RAGE, AGE and AOPP were measured using enzyme-linked immunosorbent assay (ELISA) commercially available kits. Statistical evaluation of data was performed using one-way non-parametric analysis of variance (ANOVA) with Kruskal-Wallis post hoc test.

RESULTS: Our results revealed a decline in soluble RAGE level, concurrent with an increase in the levels of AGEs and AOPPs in blood samples from ALS patients, signifying a loss of neuroprotective form of RAGE and a simultaneous increase in AGE and AOPP production and uptake at the early stage of the disease.

CONCLUSIONS: The results obtained from our study indicate that further longitudinal study of RAGE, AGE and AOPP levels would be beneficial, outlining the dynamics between RAGE and its ligand levels as the disease progresses, and making them valuable diagnostic tools and potential therapeutic targets.}, } @article {pmid38111871, year = {2023}, author = {Poletti, B and Aiello, EN and Tagini, S and Solca, F and Torre, S and Colombo, E and Maranzano, A and Bonetti, R and Schevegher, F and Morelli, C and Doretti, A and Verde, F and Barbieri, S and Mameli, F and Priori, A and Ferrucci, R and Silani, V and Cherubini, P and Pravettoni, G and Ticozzi, N}, title = {An exploratory study on counterfactual thinking in amyotrophic lateral sclerosis.}, journal = {Frontiers in psychology}, volume = {14}, number = {}, pages = {1281976}, pmid = {38111871}, issn = {1664-1078}, abstract = {OBJECTIVES: This study aimed at exploring (1) the motor and non-motor correlates of counterfactual thinking (CFT) abilities in non-demented amyotrophic lateral sclerosis (ALS) patients and (2) the ability of CFT measures to discriminate these patients from healthy controls (HCs) and patients with and without cognitive impairment.

METHODS: N = 110 ALS patients and N = 51 HCs were administered two CFT tasks, whose sum, resulting in a CFT Index (CFTI), was addressed as the outcome. Patients further underwent an in-depth cognitive, behavioral, and motor-functional evaluation. Correlational analyses were run to explore the correlates of the CFTI in patients. Logistic regressions were performed to test whether the CFTI could discriminate patients from HCs.

RESULTS: The CFTI was selectively associated (p ≤ 0.005) with fluency and memory subscales of the Edinburgh Cognitive and Behavioral ALS Screen (ECAS), but not with other variables. CFTI scores discriminated patients from HCs (p < 0.001) with high accuracy (82%), but not patients with a normal vs. defective performance on the ECAS-Total.

CONCLUSION: CFT measures in non-demented ALS patients were associated with verbal fluency and memory functions, and they were also able to discriminate them from HCs.}, } @article {pmid38111121, year = {2024}, author = {}, title = {Erratum to "Suicide among veterans with amyotrophic lateral sclerosis".}, journal = {Muscle & nerve}, volume = {69}, number = {2}, pages = {246-247}, doi = {10.1002/mus.28011}, pmid = {38111121}, issn = {1097-4598}, } @article {pmid38111057, year = {2023}, author = {Zhao, B and Cowan, CM and Coutts, JA and Christy, DD and Saraph, A and Hsueh, SCC and Plotkin, SS and Mackenzie, IR and Kaplan, JM and Cashman, NR}, title = {Targeting RACK1 to alleviate TDP-43 and FUS proteinopathy-mediated suppression of protein translation and neurodegeneration.}, journal = {Acta neuropathologica communications}, volume = {11}, number = {1}, pages = {200}, pmid = {38111057}, issn = {2051-5960}, support = {SRA F16-05805//ProMIS Neurosciences/ ; PJT-159546//Canadian Institute of Health Research/ ; CCNA-20R04367//Canadian Institute of Health Research/ ; 20R74974//Fondation Brain Canada/ ; F20-04056//Fondation Brain Canada/ ; F17-00928//William A. Lambert donation/ ; }, mesh = {Animals ; Humans ; *Amyotrophic Lateral Sclerosis/pathology ; Drosophila melanogaster/genetics/metabolism ; HEK293 Cells ; Motor Neurons/metabolism ; DNA-Binding Proteins/genetics/metabolism ; *Frontotemporal Dementia/pathology ; *Frontotemporal Lobar Degeneration/pathology ; Protein Biosynthesis ; *Sarcoma/metabolism/pathology ; RNA-Binding Protein FUS/genetics/metabolism ; Receptors for Activated C Kinase/genetics/metabolism ; Neoplasm Proteins/genetics ; }, abstract = {TAR DNA-binding protein 43 (TDP-43) and Fused in Sarcoma/Translocated in Sarcoma (FUS) are ribonucleoproteins associated with pathogenesis of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Under physiological conditions, TDP-43 and FUS are predominantly localized in the nucleus, where they participate in transcriptional regulation, RNA splicing and metabolism. In disease, however, they are typically mislocalized to the cytoplasm where they form aggregated inclusions. A number of shared cellular pathways have been identified that contribute to TDP-43 and FUS toxicity in neurodegeneration. In the present study, we report a novel pathogenic mechanism shared by these two proteins. We found that pathological FUS co-aggregates with a ribosomal protein, the Receptor for Activated C-Kinase 1 (RACK1), in the cytoplasm of spinal cord motor neurons of ALS, as previously reported for pathological TDP-43. In HEK293T cells transiently transfected with TDP-43 or FUS mutant lacking a functional nuclear localization signal (NLS; TDP-43[ΔNLS] and FUS[ΔNLS]), cytoplasmic TDP-43 and FUS induced co-aggregation with endogenous RACK1. These co-aggregates sequestered the translational machinery through interaction with the polyribosome, accompanied by a significant reduction of global protein translation. RACK1 knockdown decreased cytoplasmic aggregation of TDP-43[ΔNLS] or FUS[ΔNLS] and alleviated associated global translational suppression. Surprisingly, RACK1 knockdown also led to partial nuclear localization of TDP-43[ΔNLS] and FUS[ΔNLS] in some transfected cells, despite the absence of NLS. In vivo, RACK1 knockdown alleviated retinal neuronal degeneration in transgenic Drosophila melanogaster expressing hTDP-43[WT] or hTDP-43[Q331K] and improved motor function of hTDP-43[WT] flies, with no observed adverse effects on neuronal health in control knockdown flies. In conclusion, our results revealed a novel shared mechanism of pathogenesis for misfolded aggregates of TDP-43 and FUS mediated by interference with protein translation in a RACK1-dependent manner. We provide proof-of-concept evidence for targeting RACK1 as a potential therapeutic approach for TDP-43 or FUS proteinopathy associated with ALS and FTLD.}, } @article {pmid38110839, year = {2024}, author = {Benatar, M and Ostrow, LW and Lewcock, JW and Bennett, F and Shefner, J and Bowser, R and Larkin, P and Bruijn, L and Wuu, J}, title = {Biomarker Qualification for Neurofilament Light Chain in Amyotrophic Lateral Sclerosis: Theory and Practice.}, journal = {Annals of neurology}, volume = {95}, number = {2}, pages = {211-216}, pmid = {38110839}, issn = {1531-8249}, support = {U01 NS107027/NS/NINDS NIH HHS/United States ; U01 NS107027/NH/NIH HHS/United States ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/drug therapy ; Superoxide Dismutase-1 ; Intermediate Filaments ; Biomarkers ; Prognosis ; Neurofilament Proteins ; }, abstract = {OBJECTIVE: To explore whether the utility of neurofilament light chain (NfL), as a biomarker to aid amyotrophic lateral sclerosis (ALS) therapy development, would be enhanced by obtaining formal qualification from the US Food and Drug Administration for a defined context-of-use.

METHODS: Consensus discussion among academic, industry, and patient advocacy group representatives.

RESULTS: A wealth of scientific evidence supports the use of NfL as a prognostic, response, and potential safety biomarker in the broad ALS population, and as a risk/susceptibility biomarker among the subset of SOD1 pathogenic variant carriers. Although NfL has not yet been formally qualified for any of these contexts-of-use, the US Food and Drug Administration has provided accelerated approval for an SOD1-lowering antisense oligonucleotide, based partially on the recognition that a reduction in NfL is reasonably likely to predict a clinical benefit.

INTERPRETATION: The increasing incorporation of NfL into ALS therapy development plans provides evidence that its utility-as a prognostic, response, risk/susceptibility, and/or safety biomarker-is already widely accepted by the community. The willingness of the US Food and Drug Administration to base regulatory decisions on rigorous peer-reviewed data-absent formal qualification, leads us to conclude that formal qualification, despite some benefits, is not essential for ongoing and future use of NfL as a tool to aid ALS therapy development. Although the balance of considerations for and against seeking NfL biomarker qualification will undoubtedly vary across different diseases and contexts-of-use, the robustness of the published data and careful deliberations of the ALS community may offer valuable insights for other disease communities grappling with the same issues. ANN NEUROL 2024;95:211-216.}, } @article {pmid38110502, year = {2023}, author = {Ludolph, AC and Grandjean, H and Reviers, E and De Micheli, V and Bianchi, C and Cardosi, L and Russ, H and Silani, V}, title = {The preferences of people with amyotrophic lateral sclerosis on riluzole treatment in Europe.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {22497}, pmid = {38110502}, issn = {2045-2322}, mesh = {Humans ; Riluzole/therapeutic use ; *Amyotrophic Lateral Sclerosis/drug therapy ; Suspensions ; Europe ; *Airway Obstruction ; Tablets ; *Neuroprotective Agents ; }, abstract = {The Patient Preference Survey aims to understand unmet needs related to riluzole management in people with Amyotrophic Lateral Sclerosis (ALS) and to identify which characteristics of a new formulation could better match their preferences. The survey involved 117 people with ALS (PALS) treated with riluzole in four European countries. The dysphagic PALS were least satisfied with the riluzole tablet and oral suspension and with ease in self-administration; up to 68% of respondents postponed or missed the treatment due to swallowing difficulties and need of caregiver assistance. Overall, 51% of tablet and 53% of oral suspension users regularly crushed or mixed riluzole with beverages, respectively; PALS who always manipulated riluzole showed low satisfaction with the formulation and considered the risk of choking and pneumonia the most worrisome event. The survey evaluated the driving factors in choosing/switching the therapy: 67% of PALS declared a low risk of choking. The research finally evaluated which attributes of a new formulation would be preferred: the most relevant were ease of use (4.3/5), convenient/portable packaging (4.0/5) and oral-dissolving properties without tongue motility (3.9/5). The Patient Preference Survey suggests that patients have several unmet needs and preferences that could be addressed by a different formulation, e.g. using oral film technologies.}, } @article {pmid38110419, year = {2023}, author = {Chen, ZS and Ou, M and Taylor, S and Dafinca, R and Peng, SI and Talbot, K and Chan, HYE}, title = {Mutant GGGGCC RNA prevents YY1 from binding to Fuzzy promoter which stimulates Wnt/β-catenin pathway in C9ALS/FTD.}, journal = {Nature communications}, volume = {14}, number = {1}, pages = {8420}, pmid = {38110419}, issn = {2041-1723}, mesh = {Humans ; *Frontotemporal Dementia/genetics ; RNA ; beta Catenin/genetics/metabolism ; C9orf72 Protein/genetics ; DNA Repeat Expansion ; *Amyotrophic Lateral Sclerosis/genetics ; YY1 Transcription Factor/genetics/metabolism ; }, abstract = {The GGGGCC hexanucleotide repeat expansion mutation in the chromosome 9 open reading frame 72 (C9orf72) gene is a major genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia (C9ALS/FTD). In this study, we demonstrate that the zinc finger (ZF) transcriptional regulator Yin Yang 1 (YY1) binds to the promoter region of the planar cell polarity gene Fuzzy to regulate its transcription. We show that YY1 interacts with GGGGCC repeat RNA via its ZF and that this interaction compromises the binding of YY1 to the Fuzzy[YY1] promoter sites, resulting in the downregulation of Fuzzy transcription. The decrease in Fuzzy protein expression in turn activates the canonical Wnt/β-catenin pathway and induces synaptic deficits in C9ALS/FTD neurons. Our findings demonstrate a C9orf72 GGGGCC RNA-initiated perturbation of YY1-Fuzzy transcriptional control that implicates aberrant Wnt/β-catenin signalling in C9ALS/FTD-associated neurodegeneration. This pathogenic cascade provides a potential new target for disease-modifying therapy.}, } @article {pmid38110144, year = {2024}, author = {Hafner, C and Manschein, V and Klaus, DA and Schaubmayr, W and Tiboldi, A and Scharner, V and Gleiss, A and Thal, B and Krammel, M and Hamp, T and Willschke, H and Hermann, M}, title = {Live stream of prehospital point-of-care ultrasound during cardiopulmonary resuscitation - A feasibility trial.}, journal = {Resuscitation}, volume = {194}, number = {}, pages = {110089}, doi = {10.1016/j.resuscitation.2023.110089}, pmid = {38110144}, issn = {1873-1570}, support = {21044//Medical Scientific Fund of the Mayor of the City of Vienna/ ; }, mesh = {Humans ; *Cardiopulmonary Resuscitation/methods ; *Emergency Medical Services/methods ; Feasibility Studies ; *Out-of-Hospital Cardiac Arrest/diagnostic imaging/therapy ; Point-of-Care Systems ; }, abstract = {BACKGROUND: Current resuscitation guidelines recommend that skilled persons could use ultrasound to detect reversible causes during cardiopulmonary resuscitation (CPR) where the examination can be safely integrated into the Advanced Life Support (ALS) algorithm. However, in a prehospital setting performing and rapidly interpreting ultrasound can be challenging for physicians. Implementing remote, expert-guided, and real-time transmissions of ultrasound examinations offers the opportunity for tele-support, even during an out-of-hospital cardiac arrest (OHCA). The aim of this feasibility study was to evaluate the impact of tele-supported ultrasound in ALS on hands-off time during an OHCA.

METHODS: In an urban setting, physicians performed point-of-care ultrasound (POCUS) on patients during OHCA using a portable device, either with tele-support (n = 30) or without tele-support (n = 12). Where tele-support was used, the ultrasound image was transmitted via a remote real-time connection to an on-call specialist in anaesthesia and intensive care medicine with an advanced level of critical care ultrasound expertise. The primary safety endpoint of this study was to evaluate whether POCUS can be safely integrated into the algorithm, and to provide an analysis of hands-off time before, during, and after POCUS during OHCA.

RESULTS: In all 42 cases it was possible to perform POCUS during regular rhythm analyses, and no additional hands-off time was required. In 40 of these 42 cases, the physicians were able to perform POCUS during a single regular rhythm analysis, with two periods required only in two cases. The median hands-off time during these rhythm analyses for POCUS with tele-support was 10 (8-13) seconds, and 11 (9-14) seconds for POCUS without tele-support. Furthermore, as a result of POCUS, in a quarter of all cases the physician on scene altered their diagnosis of the primary suspected cause of cardiac arrest, leading to a change in treatment strategy.

CONCLUSIONS: This feasibility study demonstrated that POCUS with tele-support can be safely performed during OHCA in an urban environment. Trial Registration (before patient enrolment): ClinicalTrials.gov, NCT04817475.}, } @article {pmid38109536, year = {2023}, author = {Qin, F and Cai, B and Cao, R and Bai, X and Yuan, J and Zhang, Y and Liu, Y and Chen, T and Liu, F and Sun, W and Zheng, Y and Qi, X and Zhao, W and Liu, B and Gao, C}, title = {Listerin promotes cGAS protein degradation through the ESCRT pathway to negatively regulate cGAS-mediated immune response.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {120}, number = {52}, pages = {e2308853120}, pmid = {38109536}, issn = {1091-6490}, support = {32230033//MOST | National Natural Science Foundation of China (NSFC)/ ; 81930039//MOST | National Natural Science Foundation of China (NSFC)/ ; 82222027//MOST | National Natural Science Foundation of China (NSFC)/ ; 32270918//MOST | National Natural Science Foundation of China (NSFC)/ ; 31900680//MOST | National Natural Science Foundation of China (NSFC)/ ; 2021YFC2300603//MOST | National Key Research and Development Program of China (NKPs)/ ; ZR201911140289//| Natural Science Foundation of Shandong Province ()/ ; ZR2021YQ48//| Natural Science Foundation of Shandong Province ()/ ; ZR2018BC021//| Natural Science Foundation of Shandong Province ()/ ; ZR2021ZD08//| Natural Science Foundation of Shandong Province ()/ ; 82321002//MOST | National Natural Science Foundation of China (NSFC)/ ; }, mesh = {Animals ; Mice ; *Amyotrophic Lateral Sclerosis/drug therapy/immunology ; Endosomal Sorting Complexes Required for Transport/metabolism ; Immunity, Innate/genetics ; Nucleotidyltransferases/metabolism ; Proteolysis ; Signal Transduction/physiology ; Disease Models, Animal ; *Ubiquitin-Protein Ligases/antagonists & inhibitors/immunology/metabolism ; }, abstract = {The enzyme cyclic GMP-AMP synthase (cGAS) is a key sensor for detecting misplaced double-stranded DNA (dsDNA) of genomic, mitochondrial, and microbial origin. It synthesizes 2'3'-cGAMP, which in turn activates the stimulator of interferon genes pathway, leading to the initiation of innate immune responses. Here, we identified Listerin as a negative regulator of cGAS-mediated innate immune response. We found that Listerin interacts with cGAS on endosomes and promotes its K63-linked ubiquitination through recruitment of the E3 ligase TRIM27. The polyubiquitinated cGAS is then recognized by the endosomal sorting complexes required for transport machinery and sorted into endosomes for degradation. Listerin deficiency enhances the innate antiviral response to herpes simplex virus 1 infection. Genetic deletion of Listerin also deteriorates the neuroinflammation and the ALS disease progress in an ALS mice model; overexpression of Listerin can robustly ameliorate disease progression in ALS mice. Thus, our work uncovers a mechanism for cGAS regulation and suggests that Listerin may be a promising therapeutic target for ALS disease.}, } @article {pmid38109186, year = {2023}, author = {Nimma, S and Gans, A and Wardhan, R and Allen, W}, title = {Remimazolam Sedation and Neuraxial Anesthesia in a Patient with Amyotrophic Lateral Sclerosis Undergoing an Open Colectomy: A Case Report.}, journal = {A&A practice}, volume = {17}, number = {12}, pages = {e01733}, doi = {10.1213/XAA.0000000000001733}, pmid = {38109186}, issn = {2575-3126}, mesh = {Male ; Humans ; Middle Aged ; *Amyotrophic Lateral Sclerosis/complications/surgery ; *Neurodegenerative Diseases ; Benzodiazepines ; *Anesthesia, Conduction ; Colectomy ; *Respiratory Insufficiency ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease involving the upper and lower motor neurons. Perioperative management of patients with ALS can be challenging due to the risk of hemodynamic instability, aspiration, and ventilatory failure. We discuss a 58-year-old male patient with ALS who underwent open abdominal surgery under regional anesthesia utilizing a remimazolam infusion for sedation. While various sedation agents have been used successfully in patients with ALS, remimazolam, a new short-acting benzodiazepine with unique pharmacologic properties and reversible anxiolysis, provides amnesia while avoiding ventilatory depression.}, } @article {pmid38108952, year = {2024}, author = {Xiao, X and Rui, Y and Jin, Y and Chen, M}, title = {Relationship of Sleep Disorder with Neurodegenerative and Psychiatric Diseases: An Updated Review.}, journal = {Neurochemical research}, volume = {49}, number = {3}, pages = {568-582}, pmid = {38108952}, issn = {1573-6903}, support = {82371541//National Natural Science Foundation of China/ ; }, mesh = {Humans ; *Neurodegenerative Diseases/metabolism ; *Alzheimer Disease/metabolism ; Brain/metabolism ; *Huntington Disease/metabolism ; *Sleep Wake Disorders/metabolism ; }, abstract = {Sleep disorders affect many people worldwide and can accompany neurodegenerative and psychiatric diseases. Sleep may be altered before the clinical manifestations of some of these diseases appear. Moreover, some sleep disorders affect the physiological organization and function of the brain by influencing gene expression, accelerating the accumulation of abnormal proteins, interfering with the clearance of abnormal proteins, or altering the levels of related hormones and neurotransmitters, which can cause or may be associated with the development of neurodegenerative and psychiatric diseases. However, the detailed mechanisms of these effects are unclear. This review mainly focuses on the relationship between and mechanisms of action of sleep in Alzheimer's disease, depression, and anxiety, as well as the relationships between sleep and Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. This summary of current research hotspots may provide researchers with better clues and ideas to develop treatment solutions for neurodegenerative and psychiatric diseases associated with sleep disorders.}, } @article {pmid38108666, year = {2024}, author = {Clemente-Gutierrez, U and Pieterman, CRC and Lui, MS and Yamashita, TS and Tame-Elorduy, A and Huang, BL and Shirali, AS and Erstad, DJ and Lee, JE and Fisher, SB and Graham, PH and Grubbs, EG and Waguespack, SG and Ng, CS and Perrier, N}, title = {Beyond the three P's: adrenal involvement in MEN1.}, journal = {Endocrine-related cancer}, volume = {31}, number = {2}, pages = {}, pmid = {38108666}, issn = {1479-6821}, support = {P30 CA016672/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; Adult ; Middle Aged ; *Multiple Endocrine Neoplasia Type 1/pathology ; Retrospective Studies ; *Adrenal Gland Neoplasms/epidemiology ; *Adrenocortical Carcinoma ; *Adrenal Cortex Neoplasms ; }, abstract = {Adrenal lesions (ALs) are often detected in patients with multiple endocrine neoplasia type 1 (MEN1). However, they are not well described in MEN1, making their clinical management unclear. This study examined the prevalence and outcomes of ALs found in MEN1. We performed a retrospective chart review of patients diagnosed with MEN1 from 1990 to 2021. ALs were diagnosed using abdominal or thoracic imaging and classified as being unilateral or bilateral, having single or multiple nodules, and as having diffuse enlargement or not. Measurable nodular lesions were analyzed for their size and growth over time. Patients' clinical and radiographic characteristics were collected. We identified 382 patients with MEN1, 89 (23.3%) of whom had ALs. The mean age at detection was 47 ± 11.9 years. We documented 101 measurable nodular lesions (mean size, 17.5 mm; range, 3-123 mm). Twenty-seven nodules (26.7%) were smaller than 1 cm. Watchful waiting was indicated in 79 (78.2%) patients, of whom 28 (35.4%) had growing lesions. Functional lesions were diagnosed in 6 (15.8%) of 38 that had functional work-up (diagnoses: pheochromocytoma (n = 2), adrenocorticotropic hormone-dependent hypercortisolism (n = 2), hyperandrogenism (n = 1), hyperaldosteronism (n = 1)); surgery was indicated for 5 (83.3%; n = 12 nodules), 2 of whom had bilateral, diffuse adrenal enlargement. Two patients were diagnosed with adrenocortical carcinoma and two with neoplasms of uncertain malignant potential. Radiographic or clinical progression of ALs is uncommon. Malignancy should be suspected on the basis of a lesion's growth rate and size. A baseline hormonal work-up is recommended, and no further biochemical work-up is suggested when the initial assessment shows nonfunctioning lesions.}, } @article {pmid38106242, year = {2023}, author = {Wang, S and Man, X and Chen, Y and Gong, T and Gao, F and Chen, W and Wang, G and Zhao, B and Chhabra, A}, title = {Three-dimensional magnetic resonance neurography aids in detection of brachial plexus nerve root signal and size alterations in patients with amyotrophic lateral sclerosis: a case-control study.}, journal = {Quantitative imaging in medicine and surgery}, volume = {13}, number = {12}, pages = {8694-8703}, pmid = {38106242}, issn = {2223-4292}, abstract = {BACKGROUND: Since previous histopathological studies have shown a distal to proximal gradient of axonal damage in peripheral nerves of patients with amyotrophic lateral sclerosis (ALS), it would be worthwhile to evaluate consequence of such changes on magnetic resonance imaging (MRI). The aim of this study was to assess proximal-distal longitudinal signal and size alterations of brachial plexus nerve roots in ALS patients using 3-dimensional (3D) magnetic resonance neurography (MRN).

METHODS: A total of 21 ALS patients and 19 controls were evaluated. The diameters and signal-to-noise (SNR) ratio values of C5-C8 roots were measured at five points from proximal to distal sites. Student's t-test was performed to compare the differences at each point between two groups. Linear regression was performed for each nerve root, and the differences in linear regression slopes between two groups were analyzed. Receiver operating characteristic (ROC) analysis was performed for the diameter and SNR value ratio of the distal to the proximal points.

RESULTS: Interobserver agreement was excellent [intraclass correlation coefficient (ICC): 0.802-0.913]. The diameters and SNR values of C5-C8 roots showed a significant decrease (P<0.05) from proximal to distal except SNR value of C5 root in controls. The slope values of diameters in ALS were -0.01924 for C5, -0.04404 for C6, -0.06228 for C7, and -0.06464 for C8. The slope values of SNR values in ALS were -10.14 for C5, -12.86 for C6, -15.99 for C7, and -19.06 for C8. The slope of nerve diameters and SNR values for ALS patients were more negatively sloped than controls (P<0.05) except SNR values of C5 and C7 roots. The ROC analysis confirmed that the diameter and SNR value ratio could differentiate ALS patients from controls with high accuracy. The cutoff values of diameter ratio were 0.7418 for C5, 0.6952 for C6, 0.6431 for C7, and 0.7147 for C8. The cutoff values of SNR value ratio were 0.5989 for C5, 0.6516 for C6, 0.6065 for C7, and 0.6758 for C8.

CONCLUSIONS: Proximal-distal longitudinal diameters and SNR values decreased significantly for brachial plexus nerve roots in ALS patients with larger differences in slopes compared to controls. These results reflect pathophysiological changes of ALS and may be helpful in improving the diagnosis of ALS.}, } @article {pmid38105925, year = {2023}, author = {Mimic, S and Aru, B and Pehlivanoğlu, C and Sleiman, H and Andjus, PR and Yanıkkaya Demirel, G}, title = {Immunology of amyotrophic lateral sclerosis - role of the innate and adaptive immunity.}, journal = {Frontiers in neuroscience}, volume = {17}, number = {}, pages = {1277399}, pmid = {38105925}, issn = {1662-4548}, abstract = {This review aims to summarize the latest evidence about the role of innate and adaptive immunity in Amyotrophic Lateral Sclerosis (ALS). ALS is a devastating neurodegenerative disease affecting upper and lower motor neurons, which involves essential cells of the immune system that play a basic role in innate or adaptive immunity, that can be neurotoxic or neuroprotective for neurons. However, distinguishing between the sole neurotoxic or neuroprotective function of certain cells such as astrocytes can be challenging due to intricate nature of these cells, the complexity of the microenvironment and the contextual factors. In this review, in regard to innate immunity we focus on the involvement of monocytes/macrophages, microglia, the complement, NK cells, neutrophils, mast cells, and astrocytes, while regarding adaptive immunity, in addition to humoral immunity the most important features and roles of T and B cells are highlighted, specifically different subsets of CD4[+] as well as CD8[+] T cells. The role of autoantibodies and cytokines is also discussed in distinct sections of this review.}, } @article {pmid38105307, year = {2024}, author = {Hamad, AA and Amer, BE and Hawas, Y and Mabrouk, MA and Meshref, M}, title = {Masitinib as a neuroprotective agent: a scoping review of preclinical and clinical evidence.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {45}, number = {5}, pages = {1861-1873}, pmid = {38105307}, issn = {1590-3478}, mesh = {Humans ; *Neuroprotective Agents/pharmacology/therapeutic use ; Animals ; *Benzamides/pharmacology/therapeutic use ; *Thiazoles/pharmacology/therapeutic use ; *Piperidines/pharmacology/therapeutic use ; *Pyridines/pharmacology/therapeutic use ; Protein Kinase Inhibitors/pharmacology ; }, abstract = {OBJECTIVES: Masitinib, originally developed as a tyrosine kinase inhibitor for cancer treatment, has shown potential neuroprotective effects in various neurological disorders by modulating key pathways implicated in neurodegeneration. This scoping review aimed to summarize the current evidence of masitinib's neuroprotective activities from preclinical to clinical studies.

METHODS: This scoping review was conducted following the guidelines described by Arksey and O'Malley and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The inclusion criteria covered all original studies reporting on the neuroprotective effects of masitinib, including clinical studies, animal studies, and in vitro studies.

RESULTS: A total of 16 studies met the inclusion criteria and were included in the review. These comprised five randomized controlled trials (RCTs), one post-hoc analysis study, one case report, and nine animal studies. The RCTs focused on Alzheimer's disease (two studies), multiple sclerosis (two studies), and amyotrophic lateral sclerosis (one study). Across all included studies, masitinib consistently demonstrated neuroprotective properties. However, the majority of RCTs reported concerns regarding the safety profile of masitinib. Preclinical studies revealed the neuroprotective mechanisms of masitinib, which include inhibition of certain kinases interfering with cell proliferation and survival, reduction of neuroinflammation, and exhibition of antioxidant activity.

CONCLUSION: The current evidence suggests a promising therapeutic benefit of masitinib in neurodegenerative diseases. However, further research is necessary to validate and expand upon these findings, particularly regarding the precise mechanisms through which masitinib exerts its therapeutic effects. Future studies should also focus on addressing the safety concerns associated with masitinib use.}, } @article {pmid38105306, year = {2024}, author = {Katerelos, A and Alexopoulos, P and Economou, P and Polychronopoulos, P and Chroni, E}, title = {Cognitive function in amyotrophic lateral sclerosis: a cross-sectional and prospective pragmatic clinical study with review of the literature.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {45}, number = {5}, pages = {2075-2085}, pmid = {38105306}, issn = {1590-3478}, mesh = {Adult ; Humans ; *Amyotrophic Lateral Sclerosis/complications/diagnosis ; *Cognition Disorders/etiology/complications ; Neuropsychological Tests ; Prospective Studies ; Quality of Life ; Cross-Sectional Studies ; Cognition/physiology ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) can present with either bulbar or spinal symptoms, and in some cases, both types of symptoms may be present. In addition, cognitive impairment has been observed in ALS. The study aimed to evaluate the frontal and general cognitive performance in ALS not only cross-sectionally but also longitudinally.

METHODS AND MATERIALS: The Frontal Assessment Battery (FAB) and the Montreal Cognitive Assessment (MoCA) were employed to assess cognitive function in 52 adults with ALS and 52 cognitively healthy individuals. The statistical analyses encompassed the Pearson Chi square test, the Skillings-Mack test, the Spearman's rank correlation coefficient, and the Proportional Odds Logistic Regression Model (POLR).

RESULTS: Cross-sectionally, lower cognitive performance was associated with ALS diagnosis, older age, and motor functional decline. The cognitive impairment of individuals with bulbar and spinal-bulbar symptoms showed faster deterioration compared to those with spinal symptoms. The spinal subgroup consistently performed worst in delayed recall and attention, while the spinal-bulbar and bulbar subgroups exhibited inferior scores in delayed recall, attention, visuospatial skills, orientation, and verbal fluency.

CONCLUSION: The incorporation of cognitive screening in the diagnostic workup of ALS may be beneficial, as early detection can enhance symptom management and improve the quality of life for both individuals with ALS and their care partners.}, } @article {pmid38103252, year = {2024}, author = {He, L and Zhou, Q and Xiu, C and Shao, Y and Shen, D and Meng, H and Le, W and Chen, S}, title = {Circulating proteomic biomarkers for diagnosing sporadic amyotrophic lateral sclerosis: a cross-sectional study.}, journal = {Neural regeneration research}, volume = {19}, number = {8}, pages = {1842-1848}, pmid = {38103252}, issn = {1673-5374}, abstract = {JOURNAL/nrgr/04.03/01300535-202408000-00039/figure1/v/2023-12-16T180322Z/r/image-tiff Biomarkers are required for the early detection, prognosis prediction, and monitoring of amyotrophic lateral sclerosis, a progressive disease. Proteomics is an unbiased and quantitative method that can be used to detect neurochemical signatures to aid in the identification of candidate biomarkers. In this study, we used a label-free quantitative proteomics approach to screen for substantially differentially regulated proteins in ten patients with sporadic amyotrophic lateral sclerosis compared with five healthy controls. Substantial upregulation of serum proteins related to multiple functional clusters was observed in patients with sporadic amyotrophic lateral sclerosis. Potential biomarkers were selected based on functionality and expression specificity. To validate the proteomics profiles, blood samples from an additional cohort comprising 100 patients with sporadic amyotrophic lateral sclerosis and 100 healthy controls were subjected to enzyme-linked immunosorbent assay. Eight substantially upregulated serum proteins in patients with sporadic amyotrophic lateral sclerosis were selected, of which the cathelicidin-related antimicrobial peptide demonstrated the best discriminative ability between patients with sporadic amyotrophic lateral sclerosis and healthy controls (area under the curve [AUC] = 0.713, P < 0.0001). To further enhance diagnostic accuracy, a multi-protein combined discriminant algorithm was developed incorporating five proteins (hemoglobin beta, cathelicidin-related antimicrobial peptide, talin-1, zyxin, and translationally-controlled tumor protein). The algorithm achieved an AUC of 0.811 and a P-value of < 0.0001, resulting in 79% sensitivity and 71% specificity for the diagnosis of sporadic amyotrophic lateral sclerosis. Subsequently, the ability of candidate biomarkers to discriminate between early-stage amyotrophic lateral sclerosis patients and controls, as well as patients with different disease severities, was examined. A two-protein panel comprising talin-1 and translationally-controlled tumor protein effectively distinguished early-stage amyotrophic lateral sclerosis patients from controls (AUC = 0.766, P < 0.0001). Moreover, the expression of three proteins (FK506 binding protein 1A, cathelicidin-related antimicrobial peptide, and hemoglobin beta-1) was found to increase with disease progression. The proteomic signatures developed in this study may help facilitate early diagnosis and monitor the progression of sporadic amyotrophic lateral sclerosis when used in combination with current clinical-based parameters.}, } @article {pmid38103219, year = {2024}, author = {Ma, S and Zhang, CL}, title = {MAP4K inhibition as a potential therapy for amyotrophic lateral sclerosis.}, journal = {Neural regeneration research}, volume = {19}, number = {8}, pages = {1639-1640}, pmid = {38103219}, issn = {1673-5374}, support = {R01 NS092616/NS/NINDS NIH HHS/United States ; R01 NS111776/NS/NINDS NIH HHS/United States ; R01 NS117065/NS/NINDS NIH HHS/United States ; R01 NS127375/NS/NINDS NIH HHS/United States ; }, } @article {pmid38103074, year = {2023}, author = {Villavicencio-Tejo, F and Olesen, MA and Navarro, L and Calisto, N and Iribarren, C and García, K and Corsini, G and Quintanilla, RA}, title = {Gut-Brain Axis Deregulation and Its Possible Contribution to Neurodegenerative Disorders.}, journal = {Neurotoxicity research}, volume = {42}, number = {1}, pages = {4}, pmid = {38103074}, issn = {1476-3524}, support = {1200178//Agencia Nacional de Investigación y Desarrollo/ ; }, mesh = {Animals ; Humans ; Brain-Gut Axis ; *Amyotrophic Lateral Sclerosis ; *Gastrointestinal Microbiome/physiology ; *Neurodegenerative Diseases/pathology ; Central Nervous System ; *Parkinson Disease/pathology ; *Huntington Disease/pathology ; *Alzheimer Disease ; }, abstract = {The gut-brain axis is an essential communication pathway between the central nervous system (CNS) and the gastrointestinal tract. The human microbiota is composed of a diverse and abundant microbial community that compasses more than 100 trillion microorganisms that participate in relevant physiological functions such as host nutrient metabolism, structural integrity, maintenance of the gut mucosal barrier, and immunomodulation. Recent evidence in animal models has been instrumental in demonstrating the possible role of the microbiota in neurodevelopment, neuroinflammation, and behavior. Furthermore, clinical studies suggested that adverse changes in the microbiota can be considered a susceptibility factor for neurological disorders (NDs), such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS). In this review, we will discuss evidence describing the role of gut microbes in health and disease as a relevant risk factor in the pathogenesis of neurodegenerative disorders, including AD, PD, HD, and ALS.}, } @article {pmid38102715, year = {2023}, author = {Stringer, RN and Weiss, N}, title = {Pathophysiology of ion channels in amyotrophic lateral sclerosis.}, journal = {Molecular brain}, volume = {16}, number = {1}, pages = {82}, pmid = {38102715}, issn = {1756-6606}, support = {#22-23242S//Grantová Agentura České Republiky/ ; VEGA #2/0073/22//Agentúra Ministerstva Školstva, Vedy, Výskumu a Športu SR/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis ; Motor Neurons ; Ion Channels ; Muscle Weakness ; }, abstract = {Amyotrophic lateral sclerosis (ALS) stands as the most prevalent and severe form of motor neuron disease, affecting an estimated 2 in 100,000 individuals worldwide. It is characterized by the progressive loss of cortical, brainstem, and spinal motor neurons, ultimately resulting in muscle weakness and death. Although the etiology of ALS remains poorly understood in most cases, the remodelling of ion channels and alteration in neuronal excitability represent a hallmark of the disease, manifesting not only during the symptomatic period but also in the early pre-symptomatic stages. In this review, we delve into these alterations observed in ALS patients and preclinical disease models, and explore their consequences on neuronal activities. Furthermore, we discuss the potential of ion channels as therapeutic targets in the context of ALS.}, } @article {pmid38102515, year = {2024}, author = {Shen, D and Ji, Y and Qiu, C and Wang, K and Gao, Z and Liu, B and Shen, Y and Gong, L and Yang, X and Chen, X and Sun, H and Yao, X}, title = {Single-Cell RNA Sequencing Analysis of Microglia Dissected the Energy Metabolism and Revealed Potential Biomarkers in Amyotrophic Lateral Sclerosis.}, journal = {Molecular neurobiology}, volume = {61}, number = {7}, pages = {4473-4487}, pmid = {38102515}, issn = {1559-1182}, support = {92068112//National Natural Science Foundation of China/ ; 82072160//National Natural Science Foundation of China/ ; 32130060//National Natural Science Foundation of China/ ; 81901933//National Natural Science Foundation of China/ ; 20KJA310012//Major Natural Science Research Projects in Universities of Jiangsu Province/ ; BK20202013//Natural Science Foundation of Jiangsu Province/ ; BK20201209//Natural Science Foundation of Jiangsu Province/ ; JC22022037//Priority Academic Program Development of Jiangsu Higher Education Institutions/ ; MS22022010//Priority Academic Program Development of Jiangsu Higher Education Institutions/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology ; *Microglia/metabolism/pathology ; Animals ; *Energy Metabolism/genetics ; Humans ; *Biomarkers/metabolism ; *Single-Cell Analysis ; Sequence Analysis, RNA/methods ; Mice ; Mice, Transgenic ; Male ; Superoxide Dismutase-1/genetics/metabolism ; Female ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a common neurodegenerative disease, accompanied by the gradual loss of motor neuron, even life-threatening. However, the pathogenesis, early diagnosis, and effective strategies of ALS are not yet completely understood. In this study, the function of differentially expressed genes (DEGs) in non-neuronal cells of the primary motor cortex of ALS patients (DATA1), the brainstem of SOD1 mutant ALS mice (DATA2), and the whole blood tissue of ALS patients (DATA3) were explored. The results showed that the functions of DEGs in non-neuronal cells were mainly related to energy metabolism (such as oxidative phosphorylation) and protein synthesis. In non-neuronal cells, six upregulated DEGs (HSPA8, SOD1, CALM1, CALM2, NEFL, COX6C) and three downregulated DEGs (SNRNP70, HSPA1A, HSPA1B) might be key factors in regulating ALS. Microglia played a key role in the development of ALS. The expression of SOD1 and TUBA4A in microglia in DATA1 was significantly increased. The integration analysis of DEGs in DATA1 and DATA2 showed that SOD1 and CALM1 might be potential biomarkers. The integration analysis of DEGs in DATA1 and DATA3 showed that CALM2 and HSPA1A might be potential biomarkers. Cell interaction showed that the interaction between microglia and other cells was reduced in high oxidative phosphorylation states, which might be a risk factor in ALS. Our research provided evidence for the pathogenesis, early diagnosis, and potential targeted therapy for ALS.}, } @article {pmid38101818, year = {2024}, author = {Ryan, L and Rubinsztein, DC}, title = {The autophagy of stress granules.}, journal = {FEBS letters}, volume = {598}, number = {1}, pages = {59-72}, doi = {10.1002/1873-3468.14787}, pmid = {38101818}, issn = {1873-3468}, support = {//Raymond and Beverly Sackler Fund/ ; NIHR203312//NIHR Cambridge Biomedical Research Centre/ ; //UK Dementia Research Institute/ ; }, mesh = {Humans ; *Stress Granules ; Proteins ; Autophagy ; *Amyotrophic Lateral Sclerosis/genetics ; }, abstract = {Our understanding of stress granule (SG) biology has deepened considerably in recent years, and with this, increased understanding of links has been made between SGs and numerous neurodegenerative diseases. One of the proposed mechanisms by which SGs and any associated protein aggregates may become pathological is based upon defects in their autophagic clearance, and so the precise processes governing the degradation of SGs are important to understand. Mutations and disease-associated variants implicated in amyotrophic lateral sclerosis, Huntington's disease, Parkinson's disease and frontotemporal lobar dementia compromise autophagy, whilst autophagy-inhibiting drugs or knockdown of essential autophagy proteins result in the persistence of SGs. In this review, we will consider the current knowledge regarding the autophagy of SG.}, } @article {pmid38100415, year = {2023}, author = {Qi, C and Verheijen, BM and Kokubo, Y and Shi, Y and Tetter, S and Murzin, AG and Nakahara, A and Morimoto, S and Vermulst, M and Sasaki, R and Aronica, E and Hirokawa, Y and Oyanagi, K and Kakita, A and Ryskeldi-Falcon, B and Yoshida, M and Hasegawa, M and Scheres, SHW and Goedert, M}, title = {Tau filaments from amyotrophic lateral sclerosis/parkinsonism-dementia complex adopt the CTE fold.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {120}, number = {51}, pages = {e2306767120}, pmid = {38100415}, issn = {1091-6490}, support = {MC_UP_1201/25/MRC_/Medical Research Council/United Kingdom ; MC_U105184291/MRC_/Medical Research Council/United Kingdom ; R01 AG054641/AG/NIA NIH HHS/United States ; /WT_/Wellcome Trust/United Kingdom ; MC_UP_A025_1013/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/complications ; *Dementia/etiology ; *Chronic Traumatic Encephalopathy ; *Neurodegenerative Diseases ; *Parkinsonian Disorders/complications ; *Tauopathies ; Japan ; tau Proteins ; }, abstract = {The amyotrophic lateral sclerosis/parkinsonism-dementia complex (ALS/PDC) of the island of Guam and the Kii peninsula of Japan is a fatal neurodegenerative disease of unknown cause that is characterized by the presence of abundant filamentous tau inclusions in brains and spinal cords. Here, we used electron cryo-microscopy to determine the structures of tau filaments from the cerebral cortex of three cases of ALS/PDC from Guam and eight cases from Kii, as well as from the spinal cord of two of the Guam cases. Tau filaments had the chronic traumatic encephalopathy (CTE) fold, with variable amounts of Type I and Type II filaments. Paired helical tau filaments were also found in three Kii cases and tau filaments with the corticobasal degeneration fold in one Kii case. We identified a new Type III CTE tau filament, where protofilaments pack against each other in an antiparallel fashion. ALS/PDC is the third known tauopathy with CTE-type filaments and abundant tau inclusions in cortical layers II/III, the others being CTE and subacute sclerosing panencephalitis. Because these tauopathies are believed to have environmental causes, our findings support the hypothesis that ALS/PDC is caused by exogenous factors.}, } @article {pmid38100267, year = {2024}, author = {Qi, S and Peng, Y and Wang, G and Zhang, X and Liu, M and He, L}, title = {A tale of dual functions of SERF family proteins in regulating amyloid formation.}, journal = {Chembiochem : a European journal of chemical biology}, volume = {25}, number = {5}, pages = {e202300727}, doi = {10.1002/cbic.202300727}, pmid = {38100267}, issn = {1439-7633}, support = {2018YFE0202301//National Key R&D Program of China/ ; 2018YFE0202300//National Key R&D Program of China/ ; 22174151//National Natural Sciences Foundation of China/ ; 21991080//National Natural Sciences Foundation of China/ ; XDB0540000//Strategic Priority Research Program of the Chinese Academy of Sciences/ ; 2023AFA041//Hubei Provincial Natural Science Foundation of China/ ; }, mesh = {Animals ; Caenorhabditis elegans ; *Neurodegenerative Diseases ; Amyloidogenic Proteins ; Amyloid beta-Peptides ; *Alzheimer Disease ; *Caenorhabditis elegans Proteins ; }, abstract = {The abnormal aggregation of proteins is a significant pathological hallmark of diseases, such as the amyloid formation associated with fused in sarcoma protein (FUS) in frontotemporal lobar degeneration and amyotrophic lateral sclerosis diseases. Understanding which cellular components and how these components regulate the process of abnormal protein aggregation in living organisms is crucial for the prevention and treatment of neurodegenerative diseases. MOAG-4/SERF is a conserved family of proteins with rich positive charged residues, which was initially identified as an enhancer for the formation of amyloids in C. elegans. Knocking out SERF impedes the amyloid formation of various proteins, including α-synuclein and β-amyloid, which are linked to Parkinson's and Alzheimer's diseases, respectively. However, recent studies revealed SERF exhibited dual functions, as it could both promote and inhibit the fibril formation of the neurodegenerative disease-related amyloidogenic proteins. The connection between functions and structure basis of SERF in regulating the amyloid formation is still unclear. This review will outline the hallmark proteins in neurodegenerative diseases, summarize the contradictory role of the SERF protein family in promoting and inhibiting the aggregation of neurodegenerative proteins, and finally explore the potential structural basis and functional selectivity of the SERF protein.}, } @article {pmid38099851, year = {2024}, author = {Rong, P and Heidrick, L}, title = {Hierarchical Temporal Structuring of Speech: A Multiscale, Multimodal Framework to Inform the Assessment and Management of Neuromotor Speech Disorder.}, journal = {Journal of speech, language, and hearing research : JSLHR}, volume = {67}, number = {1}, pages = {92-115}, doi = {10.1044/2023_JSLHR-23-00219}, pmid = {38099851}, issn = {1558-9102}, mesh = {Humans ; *Speech ; Speech Intelligibility ; *Amyotrophic Lateral Sclerosis/complications ; Jaw ; Speech Disorders ; Speech Production Measurement ; Tongue ; Speech Acoustics ; }, abstract = {PURPOSE: Hierarchical temporal structuring of speech is the key to multiscale linguistic information transfer toward effective communication. This study investigated and linked the hierarchical temporal cues of the kinematic and acoustic modalities of natural, unscripted speech in neurologically healthy and impaired speakers.

METHOD: Thirteen individuals with amyotrophic lateral sclerosis (ALS) and 10 age-matched healthy controls performed a story-telling task. The hierarchical temporal structure of the speech stimulus was measured by (a) 26 articulatory-kinematic features characterizing the depth, phase synchronization, and coherence of temporal modulation of the tongue tip, tongue body, lower lip, and jaw, at three hierarchically nested timescales corresponding to prosodic stress, syllables, and onset-rime/phonemes, and (b) 25 acoustic features characterizing the parallel aspects of temporal modulation of five critical-spectral-band envelopes. All features were compared between groups. For each aspect of temporal modulation, the contributions of all articulatory features to the parallel acoustic features were evaluated by group.

RESULTS: Generally consistent disease impacts were identified on the articulatory and acoustic features, manifested by reduced modulation depths of most articulators and critical-spectral-band envelopes, primarily at the timescales of syllables and onset-rime/phonemes. For healthy speakers, the strongest articulatory-acoustic relationships were found for (a) jaw and lip, in modulating stress timing, and (b) tongue tip, in modulating the timing relation between onset-rime/phonemes and syllables. For speakers with ALS, the tongue body, tongue tip, and jaw all showed the greatest contributions to modulating syllable timing.

CONCLUSIONS: The observed disease impacts likely reflect reduced entrainment of speech motor activities to finer-grained linguistic events, presumably due to the dynamic constraints of the neuromuscular system. To accommodate these restrictions, speakers with ALS appear to use their residual articulatory motor capacities to accentuate and convey the perceptually most salient temporal cues underpinned by the syllable-centric parsing mechanism. This adaptive strategy has potential implications in managing neuromotor speech disorders.}, } @article {pmid38099605, year = {2024}, author = {Peverelli, S and Brusati, A and Casiraghi, V and Sorce, MN and Invernizzi, S and Santangelo, S and Morelli, C and Verde, F and Silani, V and Ticozzi, N and Ratti, A}, title = {Analysis of normal C9orf72 repeat length as possible disease modifier in amyotrophic lateral sclerosis.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {25}, number = {1-2}, pages = {207-210}, doi = {10.1080/21678421.2023.2273965}, pmid = {38099605}, issn = {2167-9223}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/epidemiology ; DNA Repeat Expansion/genetics ; C9orf72 Protein/genetics ; Mutation/genetics ; Genotype ; }, abstract = {The C9orf72 hexanucleotide repeat (HR) expansion is the main genetic cause of amyotrophic lateral sclerosis (ALS), with expansion size from 30 to >4000 units. Normal C9orf72 HR length is polymorphic (2-23 repeats) with alleles >8 units showing a low frequency in the general population. This study aimed to investigate if the normal C9orf72 HR length influences C9orf72 gene expression and acts as disease modifier in ALS patients negative for C9orf72 mutation (ALS-C9Neg). We found that the distribution of HR alleles was similar in 325 ALS-C9Neg and 303 healthy controls. Gene expression analysis in blood revealed a significant increase of total C9orf72 and V3 mRNA levels in ALS-C9Neg carrying two long alleles (L/L; ≥8 units) compared to patients homozygous for the 2-unit short allele (S/S). However, HR allele genotypes (L/L, S/L, S/S) correlated with no clinical parameters. Our data suggest that normal C9orf72 HR length does not act as disease modifier in ALS-C9Neg despite increasing gene expression.}, } @article {pmid38097873, year = {2024}, author = {Seo, J and Saurkar, S and Fernandez, GS and Das, A and Goutman, SA and Heidenreich, S}, title = {Preferences of Patients with Amyotrophic Lateral Sclerosis for Intrathecal Drug Delivery: Choosing between an Implanted Drug-Delivery Device and Therapeutic Lumbar Puncture.}, journal = {The patient}, volume = {17}, number = {2}, pages = {161-177}, pmid = {38097873}, issn = {1178-1661}, mesh = {Humans ; Middle Aged ; *Choice Behavior ; *Amyotrophic Lateral Sclerosis/drug therapy ; Spinal Puncture/adverse effects ; Patient Preference ; Europe ; }, abstract = {BACKGROUND: Novel intrathecal treatments for amyotrophic lateral sclerosis (ALS) may require delivery using lumbar puncture (LP). Implanted drug-delivery devices (IDDDs) could be an alternative but little is known about patients' preferences for intrathecal drug-delivery methods.

OBJECTIVE: We aimed to elicit preferences of patients with ALS for routine LP and IDDD use.

METHODS: A discrete choice experiment (DCE) and a threshold technique (TT) exercise were conducted online among patients with ALS in the US and Europe. In the DCE, patients made trade-offs between administration attributes. Attributes were identified from qualitative interviews. The TT elicited maximum acceptable risks (MARs) of complications from device implantation surgery. DCE data were analyzed using mixed logit to quantify relative attribute importance (RAI) as the maximum contribution of each attribute to a preference, and to estimate MARs of device failure. TT data were analyzed using interval regression. Four scenarios of LP and IDDD were compared.

RESULTS: Participants (N = 295) had a mean age of 57.7 years; most (74.2%) were diagnosed < 3 years ago. Preferences were affected by device failure risk (RAI 28.6%), administration frequency (26.4%), administration risk (19.7%), overall duration (17.8%), and appointment location (7.5%). Patients accepted a 5.6% device failure risk to reduce overall duration from 2 h to 30 min and a 3.6% risk for administration in a local clinic instead of a hospital. The average MAR of complications from implantation surgery was 29%. Patients preferred IDDD over LP in three of four scenarios.

CONCLUSION: Patients considered an IDDD as a valuable alternative to LP in multiple clinical settings.}, } @article {pmid38097540, year = {2023}, author = {Ikeda, T and Takahashi, K and Higashi, M and Komiya, H and Asano, T and Ogasawara, A and Kubota, S and Hashiguchi, S and Kunii, M and Tanaka, K and Tada, M and Doi, H and Takeuchi, H and Takei, K and Tanaka, F}, title = {Lateral olfactory tract usher substance (LOTUS), an endogenous Nogo receptor antagonist, ameliorates disease progression in amyotrophic lateral sclerosis model mice.}, journal = {Cell death discovery}, volume = {9}, number = {1}, pages = {454}, pmid = {38097540}, issn = {2058-7716}, support = {17H03561//MEXT | Japan Society for the Promotion of Science (JSPS)/ ; 18K07532//MEXT | Japan Society for the Promotion of Science (JSPS)/ ; 20H03342//MEXT | Japan Society for the Promotion of Science (JSPS)/ ; 20K07761//MEXT | Japan Society for the Promotion of Science (JSPS)/ ; }, abstract = {Nogo-Nogo receptor 1 (NgR1) signaling is significantly implicated in neurodegeneration in amyotrophic lateral sclerosis (ALS). We previously showed that lateral olfactory tract usher substance (LOTUS) is an endogenous antagonist of NgR1 that prevents all myelin-associated inhibitors (MAIs), including Nogo, from binding to NgR1. Here we investigated the role of LOTUS in ALS pathogenesis by analyzing G93A-mutated human superoxide dismutase 1 (SOD1) transgenic (Tg) mice, as an ALS model, as well as newly generated LOTUS-overexpressing SOD1 Tg mice. We examined expression profiles of LOTUS and MAIs and compared motor functions and survival periods in these mice. We also investigated motor neuron survival, glial proliferation in the lumbar spinal cord, and neuromuscular junction (NMJ) morphology. We analyzed downstream molecules of NgR1 signaling such as ROCK2, LIMK1, cofilin, and ataxin-2, and also neurotrophins. In addition, we investigated LOTUS protein levels in the ventral horn of ALS patients. We found significantly decreased LOTUS expression in both SOD1 Tg mice and ALS patients. LOTUS overexpression in SOD1 Tg mice increased lifespan and improved motor function, in association with prevention of motor neuron loss, reduced gliosis, increased NMJ innervation, maintenance of cofilin phosphorylation dynamics, decreased levels of ataxin-2, and increased levels of brain-derived neurotrophic factor (BDNF). Reduced LOTUS expression may enhance neurodegeneration in SOD1 Tg mice and ALS patients by activating NgR1 signaling, and in this study LOTUS overexpression significantly ameliorated ALS pathogenesis. LOTUS might serve as a promising therapeutic target for ALS.}, } @article {pmid38097227, year = {2023}, author = {Ebihara, S and Katsumata, T and Park, U}, title = {[Rehabilitation for Amyotrophic Lateral Sclerosis and ALS clinic].}, journal = {Brain and nerve = Shinkei kenkyu no shinpo}, volume = {75}, number = {12}, pages = {1349-1353}, doi = {10.11477/mf.1416202539}, pmid = {38097227}, issn = {1881-6096}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis ; Exercise Therapy ; *Medicine ; }, abstract = {The dysfunctions of amyotrophic lateral sclerosis (ALS) are highly variable. Rehabilitation medicine for movement disorders differs in accordance with the degree of severity. Exercise therapy should be performed while the disease is mild, with compensatory training increasing as the severity increases. Exercise therapy with a Hybrid Assistive Limb®(HAL®) is generally thought to preserve lower extremity function compared to those without HAL®. The mechanism may be effective on disused muscle fibers. ALS clinic may improve the prognosis of ALS patients.}, } @article {pmid38096766, year = {2024}, author = {Arslan, BT and Görkem Özyurt, M and İşak, B and Cecen, S and Türker, KS}, title = {Single motor unit estimation of the cutaneous silent period in ALS.}, journal = {Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology}, volume = {157}, number = {}, pages = {110-119}, doi = {10.1016/j.clinph.2023.11.013}, pmid = {38096766}, issn = {1872-8952}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis ; Motor Neurons/physiology ; Electromyography/methods ; Spine ; }, abstract = {OBJECTIVE: Recent evidence indicated that amyotrophic lateral sclerosis (ALS) also impairs spinal circuits, including those mediating cutaneous silent period (CSP). However, most studies utilised surface electromyography (sEMG), which needs more resolution to pinpoint changes at the single motoneuron level. We aimed to investigate CSP properties using single motor unit discharges in ALS.

METHODS: In mild and severe ALS patients and controls, CSP was recorded in the first dorsal interosseus and analysed using the discharge rate method, which accurately shows the inhibitory postsynaptic potentials (IPSPs) profile.

RESULTS: Our findings confirmed that the CSP latency was prolonged only in severe ALS patients. Moreover, the CSP duration was similar in each group, but late-stage ALS patients tend to have a longer CSP duration. The discharge rate method revealed a significantly longer duration (up to 150 ms) than the duration detected using sEMG. Strikingly, the motoneuron discharge rate - IPSP duration inverse relationship is lost in ALS patients, indicating a possible impairment in the motoneuron integrative properties.

CONCLUSIONS: Our data support previous findings of prolonged latency, presented input-output modifications of motoneurons, and revealed the entire course of the CSP, representing a much stronger inhibitory event than previously thought.

SIGNIFICANCE: Motoneuron integrative property modification assessed by CSP could be a new biomarker for ALS.}, } @article {pmid38096601, year = {2024}, author = {Chiba, K and Niwa, S}, title = {Autoinhibition and activation of kinesin-1 and their involvement in amyotrophic lateral sclerosis.}, journal = {Current opinion in cell biology}, volume = {86}, number = {}, pages = {102301}, doi = {10.1016/j.ceb.2023.102301}, pmid = {38096601}, issn = {1879-0410}, mesh = {Humans ; *Kinesins/metabolism ; *Amyotrophic Lateral Sclerosis ; Neurons/metabolism ; Biological Transport ; }, abstract = {Kinesin-1, composed of kinesin heavy chain and kinesin light chain, is a founding member of kinesin superfamily and transports various neuronal cargos. Kinesin-1 is one of the most abundant ATPases in the cell and thus need to be tightly regulated to avoid wastage of energy. It has been well established that kinesin-1 is regulated by the autoinhibition mechanism. This review focuses on the recent researches that have contributed to the understanding of mechanisms for the autoinhibition of kinesin-1 and its unlocking. Recent electron microscopic studies have shown an unanticipated structure of autoinhibited kinesin-1. Biochemical reconstitution have revealed detailed molecular mechanisms how the autoinhibition is unlocked. Importantly, misregulation of kinesin-1 is emerging as one of the major causes of amyotrophic lateral sclerosis.}, } @article {pmid38094423, year = {2023}, author = {Methods In Medicine, CAM}, title = {Retracted: Amyotrophic Lateral Sclerosis Symptom Score in Integrative Treatments (ALS-SSIT) for Evaluating Therapeutic Effect of Traditional Chinese Medicine: A Prospective Study.}, journal = {Computational and mathematical methods in medicine}, volume = {2023}, number = {}, pages = {9763080}, pmid = {38094423}, issn = {1748-6718}, abstract = {[This retracts the article DOI: 10.1155/2022/7594481.].}, } @article {pmid38093670, year = {2024}, author = {Oliveira Santos, M and Swash, M and de Carvalho, M}, title = {Current challenges in primary lateral sclerosis diagnosis.}, journal = {Expert review of neurotherapeutics}, volume = {24}, number = {1}, pages = {45-53}, doi = {10.1080/14737175.2023.2295010}, pmid = {38093670}, issn = {1744-8360}, mesh = {Adult ; Humans ; *Amyotrophic Lateral Sclerosis ; *Motor Neuron Disease/diagnosis ; Neuroimaging ; Diagnosis, Differential ; Biomarkers ; Multicenter Studies as Topic ; }, abstract = {INTRODUCTION: Primary lateral sclerosis (PLS) is a rare, adult-onset and slowly progressive motor neuron disorder whose clinical core is characterized by upper motor neuron (UMN) dysfunction. Its formal diagnosis is clinically based and disease duration-dependent. Differentiating PLS from other disorders involving UMN can be challenging, particularly in the early stages.

AREAS COVERED: Our review covers and discusses different aspects of the PLS field, including the diagnostic criteria and its limitations, its differential diagnosis and their major pitfalls, and the actual role of neurophysiology, neuroimaging, genetics, and molecular biomarkers. Symptomatic treatment of the different manifestations is also addressed. The authors searched MEDLINE and Scopus. They also searched the reference lists of articles identified by our search strategy and reviewed and selected those deemed relevant. They selected papers and studies based on the quality of the report, significance of the findings, and on the author's critical appraise and expertise.

EXPERT OPINION: It is important to investigate novel molecular biomarkers and plan multicenter clinical trials for PLS. However, this will require a large international project to recruit enough patients, particularly given the diagnostic uncertainty of the current clinical criteria. A better understanding of PLS pathophysiology is crucial for designing disease-targeted therapies.}, } @article {pmid38093132, year = {2023}, author = {Grigoriev, VV and Shevtsova, EF and Aksinenko, AY and Veselov, IM and Goreva, TV and Gabrelyan, AV and Bachurin, SO}, title = {New Hybrid Structures Based on Memanthine and Edaravone Molecules.}, journal = {Doklady. Biochemistry and biophysics}, volume = {512}, number = {1}, pages = {284-287}, pmid = {38093132}, issn = {1608-3091}, mesh = {*Memantine/pharmacology/chemistry ; Edaravone ; Receptors, N-Methyl-D-Aspartate ; *Adamantane/pharmacology ; }, abstract = {New hybrid structures based on memantine and edaravone molecules, in which the pyrazolone ring and adamantane fragments are linked by an alkyl linker, were synthesized. It was found that, in addition to the ability to block the intrachannel site of NMDA receptors, the new hybrid compounds exhibit the property of blockers of the allosteric site of NMDA receptors, which is not inherent in memantine and edaravone preparations. The most active hit compound was determined, which, along with the properties of a two-site blocker of the NMDA receptor, exhibits a pronounced activity as an inhibitor of lipid peroxidation, similarly to the drug edaravone.}, } @article {pmid38092849, year = {2023}, author = {Ou, Y and Zhao, Y}, title = {On enhancing the noise-reduction performance of the acoustic lined duct utilizing the phase-modulating metasurface.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {22184}, pmid = {38092849}, issn = {2045-2322}, abstract = {This work proposes a noise-reduction structure that integrates phase-modulating metasurface (PMM) with acoustic liners (ALs) to enhance the narrow band absorption performance of a duct with relatively small length-diameter ratio. The PMM manipulates the wavefront by introducing different transmission phase shifts based on an array of Helmholtz resonators, so that the spinning wave within the duct can be generated. Compared with the plane wave, the generated spinning wave has a lower group velocity, which results in a greater traveling distance over the ALs in the duct. The optimization design is performed to determine the final structural parameters of the PMM, which is based on the predictions of the amplitude and phase shift of the acoustic wave at the outlet of the PMM using the theory of passive phased array. With the manipulation of the PMM, the incident plane wave is modulated into a spinning wave, and then enters into the acoustic liner duct (ALD), whose structural parameters are optimized by maximizing the transmission loss using the mode-matching technique. Finally, the noise-reduction performance of this combined structure is evaluated by numerical simulations in the presence of grazing flow. The results demonstrate that, compared with the traditional ALD, the proposed structure exhibits a significant increase in transmission loss within the considered frequency band, especially near the peak frequency of the narrow band noise.}, } @article {pmid38092738, year = {2023}, author = {Raguseo, F and Wang, Y and Li, J and Petrić Howe, M and Balendra, R and Huyghebaert, A and Vadukul, DM and Tanase, DA and Maher, TE and Malouf, L and Rubio-Sánchez, R and Aprile, FA and Elani, Y and Patani, R and Di Michele, L and Di Antonio, M}, title = {The ALS/FTD-related C9orf72 hexanucleotide repeat expansion forms RNA condensates through multimolecular G-quadruplexes.}, journal = {Nature communications}, volume = {14}, number = {1}, pages = {8272}, pmid = {38092738}, issn = {2041-1723}, support = {/WT_/Wellcome Trust/United Kingdom ; MR/S006591/1/MRC_/Medical Research Council/United Kingdom ; MR/S033947/1/MRC_/Medical Research Council/United Kingdom ; SGL027\1022/AMS_/Academy of Medical Sciences/United Kingdom ; }, mesh = {Humans ; *Frontotemporal Dementia/genetics ; *Amyotrophic Lateral Sclerosis/genetics ; RNA/genetics/chemistry ; *G-Quadruplexes ; C9orf72 Protein/genetics ; DNA Repeat Expansion/genetics ; }, abstract = {Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are neurodegenerative diseases that exist on a clinico-pathogenetic spectrum, designated ALS/FTD. The most common genetic cause of ALS/FTD is expansion of the intronic hexanucleotide repeat (GGGGCC)n in C9orf72. Here, we investigate the formation of nucleic acid secondary structures in these expansion repeats, and their role in generating condensates characteristic of ALS/FTD. We observe significant aggregation of the hexanucleotide sequence (GGGGCC)n, which we associate to the formation of multimolecular G-quadruplexes (mG4s) by using a range of biophysical techniques. Exposing the condensates to G4-unfolding conditions leads to prompt disassembly, highlighting the key role of mG4-formation in the condensation process. We further validate the biological relevance of our findings by detecting an increased prevalence of G4-structures in C9orf72 mutant human motor neurons when compared to healthy motor neurons by staining with a G4-selective fluorescent probe, revealing signal in putative condensates. Our findings strongly suggest that RNA G-rich repetitive sequences can form protein-free condensates sustained by multimolecular G-quadruplexes, highlighting their potential relevance as therapeutic targets for C9orf72 mutation-related ALS/FTD.}, } @article {pmid38092667, year = {2024}, author = {Canosa, A and Cabras, S and Di Pede, F and Manera, U and Vasta, R and Moglia, C and Calvo, A and Gallone, S and Chiò, A}, title = {A mother and her daughter carrying a pathogenic expansion of the HTT gene with a phenotype encompassing motor neuron disease and Huntington's disease.}, journal = {Clinical genetics}, volume = {105}, number = {4}, pages = {430-433}, doi = {10.1111/cge.14472}, pmid = {38092667}, issn = {1399-0004}, support = {PRIN-2017SNW5MB//Ministero dell'Istruzione, dell'Università e della Ricerca/ ; RF-2016-02362405//Ministero della Salute/ ; }, mesh = {Female ; Humans ; *Amyotrophic Lateral Sclerosis/genetics ; *Huntington Disease/genetics/pathology ; Mothers ; Nuclear Family ; *Frontotemporal Dementia ; *Motor Neuron Disease/genetics ; Phenotype ; Huntingtin Protein/genetics ; }, abstract = {Recently, pathogenic expansions (range 40-64 CAG repeats) in the HTT gene have been found in patients diagnosed with pure frontotemporal dementia/amyotrophic lateral sclerosis (FTD/ALS). We report a mother with Huntington's disease (HD) associated with motor neuron disease (MND) signs and her daughter suffering from ALS with subtle signs of HD, both carrying a pathogenic allele of the HTT gene (i.e., >39 repeats). The co-occurrence of MND and chorea has been reported in previous cases. Subjects showing both ALS and HD signs and carrying HTT pathogenic expansions in two generations of the same kindred have never been reported so far. The study of the overlap of disease mechanisms at the cellular level between TDP-43 and Huntingtin is relevant in an era offering promising strategies of targeted treatments in neurodegenerative disorders.}, } @article {pmid38092270, year = {2024}, author = {Deng, C and Chen, H}, title = {Brain-derived neurotrophic factor/tropomyosin receptor kinase B signaling in spinal muscular atrophy and amyotrophic lateral sclerosis.}, journal = {Neurobiology of disease}, volume = {190}, number = {}, pages = {106377}, doi = {10.1016/j.nbd.2023.106377}, pmid = {38092270}, issn = {1095-953X}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis ; Brain-Derived Neurotrophic Factor ; Motor Neurons/physiology ; Tropomyosin ; *Muscular Atrophy, Spinal ; Receptor, trkB ; }, abstract = {Tropomyosin receptor kinase B (TrkB) and its primary ligand brain-derived neurotrophic factor (BDNF) are expressed in the neuromuscular system, where they affect neuronal survival, differentiation, and functions. Changes in BDNF levels and full-length TrkB (TrkB-FL) signaling have been revealed in spinal muscular atrophy (SMA) and amyotrophic lateral sclerosis (ALS), two common forms of motor neuron diseases that are characterized by defective neuromuscular junctions in early disease stages and subsequently progressive muscle weakness. This review summarizes the current understanding of BDNF/TrkB-FL-related research in SMA and ALS, with an emphasis on their alterations in the neuromuscular system and possible BDNF/TrkB-FL-targeting therapeutic strategies. The limitations of current studies and future directions are also discussed, giving the hope of discovering novel and effective treatments.}, } @article {pmid38090719, year = {2023}, author = {Brusati, A and Peverelli, S and Calzari, L and Tiloca, C and Casiraghi, V and Sorce, MN and Invernizzi, S and Carbone, E and Cavagnola, R and Verde, F and Silani, V and Ticozzi, N and Ratti, A and Gentilini, D}, title = {Exploring epigenetic drift and rare epivariations in amyotrophic lateral sclerosis by epigenome-wide association study.}, journal = {Frontiers in aging neuroscience}, volume = {15}, number = {}, pages = {1272135}, pmid = {38090719}, issn = {1663-4365}, abstract = {During the last decades, our knowledge about the genetic architecture of sporadic amyotrophic lateral sclerosis (sALS) has significantly increased. However, besides the recognized genetic risk factors, also the environment is supposed to have a role in disease pathogenesis. Epigenetic modifications reflect the results of the interaction between environmental factors and genes and may play a role in the development and progression of ALS. A recent epigenome-wide association study (EWAS) in blood identified differentially methylated positions mapping to 42 genes involved in cholesterol biosynthesis and immune-related pathways. Here we performed a genome-wide DNA methylation analysis in the blood of an Italian cohort of 61 sALS patients and 61 healthy controls. Initially, a conventional genome-wide association analysis was performed, and results were subsequently integrated with the findings from the previous EWAS using a meta-analytical approach. To delve deeper into the significant outcomes, over-representation analysis (ORA) was employed. Moreover, the epigenetic signature obtained from the meta-analysis was examined to determine potential associations with chemical compounds, utilizing the Toxicogenomic Database. Expanding the scope of the epigenetic analysis, we explored both epigenetic drift and rare epivariations. Notably, we observed an elevated epigenetic drift in sALS patients compared to controls, both at a global and single gene level. Interestingly, epigenetic drift at a single gene level revealed an enrichment of genes related to the neurotrophin signaling pathway. Moreover, for the first time, we identified rare epivariations exclusively enriched in sALS cases associated with 153 genes, 88 of whom with a strong expression in cerebral areas. Overall, our study reinforces the evidence that epigenetics may contribute to the pathogenesis of ALS and that epigenetic drift may be a useful diagnostic marker. Moreover, this study suggests the potential role of epivariations in ALS.}, } @article {pmid38090405, year = {2023}, author = {Gupta, D and Vagha, S and Dhingra, H and Shirsath, H}, title = {Advances in Understanding and Treating Amyotrophic Lateral Sclerosis (ALS): A Comprehensive Review.}, journal = {Cureus}, volume = {15}, number = {11}, pages = {e48691}, pmid = {38090405}, issn = {2168-8184}, abstract = {Amyotrophic lateral sclerosis (ALS) is a deadly CNS neurodegenerative disease. The way ALS is now managed, from diagnosis to prognosis, is still not ideal despite many studies. Early diagnosis can help ALS patients live longer since prompt treatment can halt the disease's development. Two medications, riluzole and edaravone, have recently been licensed for use in therapy, and they very slightly increase life expectancy. Still, a lot of cutting-edge experimental medications are being developed. In the following article, we give a synopsis of the innovative medications and genetic remodeling that have emerged recently and help to halt the course of the illness. Studies have also been conducted on a few symptomatic and rehabilitative therapies that enhance the quality of life for ALS patients.}, } @article {pmid38090276, year = {2023}, author = {}, title = {Correction to: Urinary biomarkers for amyotrophic lateral sclerosis: candidates, opportunities and considerations.}, journal = {Brain communications}, volume = {5}, number = {6}, pages = {fcad334}, doi = {10.1093/braincomms/fcad334}, pmid = {38090276}, issn = {2632-1297}, abstract = {[This corrects the article DOI: 10.1093/braincomms/fcad287.].}, } @article {pmid38088823, year = {2023}, author = {Hannan, AJ}, title = {Expanding horizons of tandem repeats in biology and medicine: Why 'genomic dark matter' matters.}, journal = {Emerging topics in life sciences}, volume = {7}, number = {3}, pages = {239-247}, pmid = {38088823}, issn = {2397-8554}, abstract = {Approximately half of the human genome includes repetitive sequences, and these DNA sequences (as well as their transcribed repetitive RNA and translated amino-acid repeat sequences) are known as the repeatome. Within this repeatome there are a couple of million tandem repeats, dispersed throughout the genome. These tandem repeats have been estimated to constitute ∼8% of the entire human genome. These tandem repeats can be located throughout exons, introns and intergenic regions, thus potentially affecting the structure and function of tandemly repetitive DNA, RNA and protein sequences. Over more than three decades, more than 60 monogenic human disorders have been found to be caused by tandem-repeat mutations. These monogenic tandem-repeat disorders include Huntington's disease, a variety of ataxias, amyotrophic lateral sclerosis and frontotemporal dementia, as well as many other neurodegenerative diseases. Furthermore, tandem-repeat disorders can include fragile X syndrome, related fragile X disorders, as well as other neurological and psychiatric disorders. However, these monogenic tandem-repeat disorders, which were discovered via their dominant or recessive modes of inheritance, may represent the 'tip of the iceberg' with respect to tandem-repeat contributions to human disorders. A previous proposal that tandem repeats may contribute to the 'missing heritability' of various common polygenic human disorders has recently been supported by a variety of new evidence. This includes genome-wide studies that associate tandem-repeat mutations with autism, schizophrenia, Parkinson's disease and various types of cancers. In this article, I will discuss how tandem-repeat mutations and polymorphisms could contribute to a wide range of common disorders, along with some of the many major challenges of tandem-repeat biology and medicine. Finally, I will discuss the potential of tandem repeats to be therapeutically targeted, so as to prevent and treat an expanding range of human disorders.}, } @article {pmid38087950, year = {2024}, author = {Metzger, M and Dukic, S and McMackin, R and Giglia, E and Mitchell, M and Bista, S and Costello, E and Peelo, C and Tadjine, Y and Sirenko, V and Plaitano, S and Coffey, A and McManus, L and Farnell Sharp, A and Mehra, P and Heverin, M and Bede, P and Muthuraman, M and Pender, N and Hardiman, O and Nasseroleslami, B}, title = {Functional network dynamics revealed by EEG microstates reflect cognitive decline in amyotrophic lateral sclerosis.}, journal = {Human brain mapping}, volume = {45}, number = {1}, pages = {e26536}, pmid = {38087950}, issn = {1097-0193}, support = {/WT_/Wellcome Trust/United Kingdom ; 16/ERCD/3854/SFI_/Science Foundation Ireland/Ireland ; URF\R1\221917/SFI_/Science Foundation Ireland/Ireland ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis ; Electroencephalography ; Retrospective Studies ; Brain ; Brain Mapping ; *Cognitive Dysfunction/etiology ; }, abstract = {Recent electroencephalography (EEG) studies have shown that patterns of brain activity can be used to differentiate amyotrophic lateral sclerosis (ALS) and control groups. These differences can be interrogated by examining EEG microstates, which are distinct, reoccurring topographies of the scalp's electrical potentials. Quantifying the temporal properties of the four canonical microstates can elucidate how the dynamics of functional brain networks are altered in neurological conditions. Here we have analysed the properties of microstates to detect and quantify signal-based abnormality in ALS. High-density resting-state EEG data from 129 people with ALS and 78 HC were recorded longitudinally over a 24-month period. EEG topographies were extracted at instances of peak global field power to identify four microstate classes (labelled A-D) using K-means clustering. Each EEG topography was retrospectively associated with a microstate class based on global map dissimilarity. Changes in microstate properties over the course of the disease were assessed in people with ALS and compared with changes in clinical scores. The topographies of microstate classes remained consistent across participants and conditions. Differences were observed in coverage, occurrence, duration, and transition probabilities between ALS and control groups. The duration of microstate class B and coverage of microstate class C correlated with lower limb functional decline. The transition probabilities A to D, C to B and C to B also correlated with cognitive decline (total ECAS) in those with cognitive and behavioural impairments. Microstate characteristics also significantly changed over the course of the disease. Examining the temporal dependencies in the sequences of microstates revealed that the symmetry and stationarity of transition matrices were increased in people with late-stage ALS. These alterations in the properties of EEG microstates in ALS may reflect abnormalities within the sensory network and higher-order networks. Microstate properties could also prospectively predict symptom progression in those with cognitive impairments.}, } @article {pmid38087504, year = {2024}, author = {Dellar, ER and Vendrell, I and Talbot, K and Kessler, BM and Fischer, R and Turner, MR and Thompson, AG}, title = {Data-independent acquisition proteomics of cerebrospinal fluid implicates endoplasmic reticulum and inflammatory mechanisms in amyotrophic lateral sclerosis.}, journal = {Journal of neurochemistry}, volume = {168}, number = {2}, pages = {115-127}, pmid = {38087504}, issn = {1471-4159}, support = {MR/K01014X/1/MRC_/Medical Research Council/United Kingdom ; TURNER/JAN13/944-795/MNDA_/Motor Neurone Disease Association/United Kingdom ; TURNER/OCT18/989-797/MNDA_/Motor Neurone Disease Association/United Kingdom ; G0701923/MRC_/Medical Research Council/United Kingdom ; MR/T006927/1/MRC_/Medical Research Council/United Kingdom ; Thompson/Jan20/952-795/MNDA_/Motor Neurone Disease Association/United Kingdom ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis ; Proteomics/methods ; Biomarkers/cerebrospinal fluid ; Prognosis ; Mass Spectrometry ; }, abstract = {While unbiased proteomics of human cerebrospinal fluid (CSF) has been used successfully to identify biomarkers of amyotrophic lateral sclerosis (ALS), high-abundance proteins mask the presence of lower abundance proteins that may have diagnostic and prognostic value. However, developments in mass spectrometry (MS) proteomic data acquisition methods offer improved protein depth. In this study, MS with library-free data-independent acquisition (DIA) was used to compare the CSF proteome of people with ALS (n = 40), healthy (n = 15) and disease (n = 8) controls. Quantified protein groups were subsequently correlated with clinical variables. Univariate analysis identified 7 proteins, all significantly upregulated in ALS versus healthy controls, and 9 with altered abundance in ALS versus disease controls (FDR < 0.1). Elevated chitotriosidase-1 (CHIT1) was common to both comparisons and was proportional to ALS disability progression rate (Pearson r = 0.41, FDR-adjusted p = 0.035) but not overall survival. Ubiquitin carboxyl-terminal hydrolase isozyme L1 (UCHL1; upregulated in ALS versus healthy controls) was proportional to disability progression rate (Pearson r = 0.53, FDR-adjusted p = 0.003) and survival (Kaplan Meier log-rank p = 0.013) but not independently in multivariate proportional hazards models. Weighted correlation network analysis was used to identify functionally relevant modules of proteins. One module, enriched for inflammatory functions, was associated with age at symptom onset (Pearson r = 0.58, FDR-adjusted p = 0.005) and survival (Hazard Ratio = 1.78, FDR = 0.065), and a second module, enriched for endoplasmic reticulum proteins, was negatively correlated with disability progression rate (r = -0.42, FDR-adjusted p = 0.109). DIA acquisition methodology therefore strengthened the biomarker candidacy of CHIT1 and UCHL1 in ALS, while additionally highlighted inflammatory and endoplasmic reticulum proteins as novel sources of prognostic biomarkers.}, } @article {pmid38087359, year = {2023}, author = {Nayab, DE and Din, FU and Ali, H and Kausar, WA and Urooj, S and Zafar, M and Khan, I and Shabbir, K and Khan, GM}, title = {Nano biomaterials based strategies for enhanced brain targeting in the treatment of neurodegenerative diseases: an up-to-date perspective.}, journal = {Journal of nanobiotechnology}, volume = {21}, number = {1}, pages = {477}, pmid = {38087359}, issn = {1477-3155}, support = {20-14604/NRPU/R&D/HEC/2021//Higher Education Commision, Pakistan/ ; }, mesh = {Humans ; *Neurodegenerative Diseases/drug therapy ; Brain ; Blood-Brain Barrier ; Drug Delivery Systems/methods ; Nanotechnology ; }, abstract = {Neurons and their connecting axons gradually degenerate in neurodegenerative diseases (NDs), leading to dysfunctionality of the neuronal cells and eventually their death. Drug delivery for the treatment of effected nervous system is notoriously complicated because of the presence of natural barriers, i.e., the blood-brain barrier and the blood cerebrospinal fluid barrier. Palliative care is currently the standard care for many diseases. Therefore, treatment programs that target the disease's origin rather than its symptoms are recommended. Nanotechnology-based drug delivery platforms offer an innovative way to circumvent these obstacles and deliver medications directly to the central nervous system, thereby enabling treatment of several common neurological problems, i.e., Alzheimer's, Parkinson's, Huntington's, and amyotrophic lateral sclerosis. Interestingly, the combination of nanomedicine and gene therapy enables targeting of selective mutant genes responsible for the progression of NDs, which may provide a much-needed boost in the struggle against these diseases. Herein, we discussed various central nervous system delivery obstacles, followed by a detailed insight into the recently developed techniques to restore neurological function via the differentiation of neural stem cells. Moreover, a comprehensive background on the role of nanomedicine in controlling neurogenesis via differentiation of neural stem cells is explained. Additionally, numerous phytoconstituents with their neuroprotective properties and molecular targets in the identification and management of NDs are also deliberated. Furthermore, a detailed insight of the ongoing clinical trials and currently marketed products for the treatment of NDs is provided in this manuscript.}, } @article {pmid38086894, year = {2024}, author = {Kraft, S and Mease, C and Jillapalli, D and Fermaglich, LJ and Miller, KL}, title = {Trends in drug development for amyotrophic lateral sclerosis.}, journal = {Nature reviews. Drug discovery}, volume = {23}, number = {2}, pages = {99-100}, doi = {10.1038/d41573-023-00199-2}, pmid = {38086894}, issn = {1474-1784}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis ; Drug Development ; }, } @article {pmid38086800, year = {2023}, author = {Wei, J and Li, M and Ye, Z and Hu, X and He, X and Wang, J and Chen, G and Zou, C and Xu, D and Zhang, H and Yuan, J and Zha, Y}, title = {Elevated peripheral levels of receptor-interacting protein kinase 1 (RIPK1) and IL-8 as biomarkers of human amyotrophic lateral sclerosis.}, journal = {Signal transduction and targeted therapy}, volume = {8}, number = {1}, pages = {451}, pmid = {38086800}, issn = {2059-3635}, support = {WJ2021M257//Health and Family Planning Commission of Hubei Province (Hubei Provincial Health Department)/ ; 2019SHZDZX02//Science and Technology Commission of Shanghai Municipality (Shanghai Municipal Science and Technology Commission)/ ; 32070737//National Natural Science Foundation of China (National Science Foundation of China)/ ; 82188101, 91849204, 21837004, 92049303 and 32170755//National Natural Science Foundation of China (National Science Foundation of China)/ ; 20JC1411600//Shanghai Science and Technology Development Foundation (Shanghai Science and Technology Development Fund)/ ; 20QA1411500//Shanghai Science and Technology Development Foundation (Shanghai Science and Technology Development Fund)/ ; }, mesh = {Animals ; Humans ; Mice ; *Amyotrophic Lateral Sclerosis/drug therapy/genetics/metabolism ; Biomarkers ; Interleukin-8/genetics ; Mice, Transgenic ; Motor Neurons/metabolism/pathology ; *Neurodegenerative Diseases/metabolism ; Primidone/metabolism/pharmacology/therapeutic use ; Protein Kinases/metabolism ; Receptor-Interacting Protein Serine-Threonine Kinases/genetics/metabolism/pharmacology ; Superoxide Dismutase/metabolism/pharmacology/therapeutic use ; Superoxide Dismutase-1/genetics/metabolism/pharmacology ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a devastating fatal neurodegenerative disease with no cure. Receptor-interacting protein kinase 1 (RIPK1) has been proposed to mediate pathogenesis of ALS. Primidone has been identified as an old drug that can also inhibit RIPK1 kinase. We conducted a drug-repurposing biomarker study of primidone as a RIPK1 inhibitor using SOD1[G93A] mice and ALS patients. SOD1[G93A] mice treated with primidone showed significant delay of symptomatic onset and improved motor performance. One-hundred-sixty-two ALS participants dosed daily with primidone (62.5 mg) completed 24-week follow-up. A significant reduction was showed in serum levels of RIPK1 and IL-8, which were significantly higher in ALS patients than that of healthy controls (P < 0.0001). Serum RIPK1 levels were correlated positively with the severity of bulbar symptoms (P < 0.05). Our study suggests that serum levels of RIPK1 and IL-8 in peripheral can be used as clinical biomarkers for the activation of RIPK1 in central nervous system in human ALS patients. Repurposing primidone may provide a promising therapeutic strategy for ALS. The effect of primidone for the treatment of other inflammatory diseases may also be considered, since the activation of RIPK1 has been implicated in mediating a variety of inflammatory diseases including COVID-19-associated cytokine release syndrome (CRS). (ChiCTR2200060149).}, } @article {pmid38084484, year = {2023}, author = {Reniers, PWA and Leontjevas, R and Declercq, IJN and Molog, M and Enders-Slegers, MJ and Gerritsen, DL and Hediger, K}, title = {[Not Available].}, journal = {Tijdschrift voor gerontologie en geriatrie}, volume = {}, number = {4}, pages = {}, doi = {10.54195/tgg.18095}, pmid = {38084484}, issn = {0167-9228}, abstract = {Achtergrond: Huisdieren zijn belangrijk in het leven van thuiswonende ouderen en van degenen die langdurige thuiszorg (LTZ) ontvangen. Het doel van dit project was om de betekenis van huisdieren voor thuiswonende ouderen te verkennen en te onderzoeken of deze ook van toepassing zijn op LTZ-cliënten. Daarnaast exploreerden we mogelijke huisdiergerelateerde uitdagingen en de invloed van huisdierbezit op zorgrelaties in de LTZ. Methoden: Het project startte met een systematische kwalitatieve literatuur review gevolgd door een studie met de Consensual Qualitative Research (CQR) methode en een onlinevragenlijst om de resultaten van de review in de LTZ te toetsen. LTZ-cliënten, mantelzorgers en professionele zorgverleners namen deel aan de CQR-studie en vragenlijst. De vragenlijst bevatte daarnaast open vragen over mogelijke huisdiergerelateerde uitdagingen en hun invloed op zorgrelaties in de LTZ. Resultaten: De review bevatte vijftien artikelen die achtentwintig rollen gerelateerd aan de betekenis van huisdieren beschreven, onderverdeeld in zeven categorieën. De uitkomsten van de CQR-studie en vragenlijst toonden dat huisdieren een vergelijkbare betekenis hebben voor thuiswonende ouderen en LTZ-cliënten. Deelnemers rapporteerden mogelijke uitdagingen en zowel positieve als negatieve effecten van huisdieren op zorgrelaties. Conclusies: Huisdieren hebben een vergelijkbare betekenis voor thuiswonende ouderen en LTZ-cliënten. Bovendien ervaren LTZ-cliënten mogelijke specifieke huisdiergerelateerde uitdagingen en kunnen huisdieren zorgrelaties beïnvloeden. Daarom is het noodzakelijk om rekening te houden met huisdieren in de LTZ.}, } @article {pmid38084253, year = {2023}, author = {Minić, R and Arsić, A and Kojadinović, M and Palibrk, A and Đorđević, B and Stević, Z}, title = {Erythrocyte fatty acid aberrations in Amyotrophic Lateral Sclerosis: Correlation with disease duration.}, journal = {Journal of medical biochemistry}, volume = {42}, number = {4}, pages = {621-629}, pmid = {38084253}, issn = {1452-8258}, abstract = {BACKGROUND: Recent literature data highlights metabolic changes in amyotrophic lateral sclerosis (ALS). To explore possible early metabolic changes, we aimed to analyse the fatty acids (FA) composition of erythrocytes in newly diagnosed als patients and to see whether fatty acid levels correlate with the ALSFRS-R score or disease duration.

METHODS: The severity of motor function involvement was assessed by the ALSFRS-R scale at the initial evaluation. The fatty acid profile of erythrocyte membranes was analysed by gas-liquid chromatography. The study comprised 26 clinically diagnosed als patients, with mean ALSFRS-R 38±8. The control group included 26 healthy volunteers.}, } @article {pmid38083843, year = {2024}, author = {Zhang, S and Li, L and Liu, X and Zhong, Q}, title = {The hookup model of the HOPS complex in autophagosome-lysosome fusion.}, journal = {Autophagy}, volume = {20}, number = {3}, pages = {714-715}, pmid = {38083843}, issn = {1554-8635}, mesh = {*Macroautophagy ; C9orf72 Protein/metabolism ; *Autophagy ; Autophagosomes/metabolism ; Membrane Fusion/physiology ; SNARE Proteins/metabolism ; Lysosomes/metabolism ; }, abstract = {Macroautophagy/autophagy is a highly conserved process that involves the degradation of proteins, damaged organelles, and other cytoplasmic macromolecules. Autophagosome-lysosome fusion is critical for successful substrate degradation and is mediated by SNARE proteins. The fusion process requires additional vesicle docking and tethering-regulating factors. Our recent work has uncovered a functional model of autophagosome-lysosome fusion. We demonstrated that the six-subunit homotypic fusion and vacuole protein sorting (HOPS) complex can be assembled by two subcomplexes, the VPS39-VPS11 subcomplex (HOPS-2) and the VPS41-VPS16-VPS18-VPS33A subcomplex (HOPS-4). VPS39 binds with RAB2 on the autophagosome and VPS41 binds with RAB39A on the lysosome, which then promotes membrane tethering and autophagic SNARE-mediated membrane fusion. Moreover, we have revealed that ALS- and FTD-related C9orf72 is a guanine exchange factor (GEF) for RAB39A. In this punctum, we discuss how the C9orf72-RAB39A-HOPS axis function regulates autophagosome-lysosome fusion.}, } @article {pmid38083694, year = {2023}, author = {Migliorelli, L and Moccia, S and Berardini, D and Frontoni, E and Coccia, M and Villani, L and Bandini, A}, title = {A preliminary study on self-care telemonitoring of dysarthria in spinal muscular atrophy.}, journal = {Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference}, volume = {2023}, number = {}, pages = {1-4}, doi = {10.1109/EMBC40787.2023.10340908}, pmid = {38083694}, issn = {2694-0604}, mesh = {Humans ; Dysarthria/diagnosis/etiology ; Self Care ; *Muscular Atrophy, Spinal/complications/diagnosis ; *Amyotrophic Lateral Sclerosis/complications ; Rare Diseases ; }, abstract = {Spinal muscular atrophy (SMA) is a rare neuromuscular disease which may cause impairments in oro-facial musculature. Most of the individuals with SMA present bulbar signs such as flaccid dysarthria which mines their abilities to speak and, as consequence, their psychic balance. To support clinicians, recent work has demonstrated the feasibility of video-based techniques for assessing the oro-facial functions in patients with neurological disorders such as amyotrophic lateral sclerosis. However, no work has so far focused on automatic and quantitative monitoring of dysarthria in SMA. To overcome limitations this work's aim is to propose a cloud-based store-and-forward telemonitoring system for automatic and quantitative evaluation of oro-facial muscles in individuals with SMA. The system integrates a convolutional neural network (CNN) aimed at identifying the position of facial landmarks from video recordings acquired via a web application by an SMA patient.Clinical relevance- The proposed work is in the preliminary stage, but it represents the first step towards a better understanding of the bulbar-functions' evolution in patients with SMA.}, } @article {pmid38082727, year = {2023}, author = {Khan, SU and Majid, M and Linguraru, MG and Muhammad Anwar, S}, title = {Upper Limb Movement Execution Classification using Electroencephalography for Brain Computer Interface.}, journal = {Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference}, volume = {2023}, number = {}, pages = {1-4}, doi = {10.1109/EMBC40787.2023.10341008}, pmid = {38082727}, issn = {2694-0604}, mesh = {Humans ; *Brain-Computer Interfaces ; Upper Extremity ; Electroencephalography/methods ; Movement ; Motion ; }, abstract = {An accurate classification of upper limb movements using electroencephalogram (EEG) signals is gaining significant importance in recent years due to the prevalence of brain-computer interfaces. The upper limbs in the human body are crucial since different skeletal segments combine to make a range of motions that helps us in our trivial daily tasks. Decoding EEG-based upper limb movements can be of great help to people with spinal cord injury (SCI) or other neuro-muscular diseases such as amyotrophic lateral sclerosis (ALS), primary lateral sclerosis, and periodic paralysis. This can manifest in a loss of sensory and motor function, which could make a person reliant on others to provide care in day-to-day activities. We can detect and classify upper limb movement activities, whether they be executed or imagined using an EEG-based brain-computer interface (BCI). Toward this goal, we focus our attention on decoding movement execution (ME) of the upper limb in this study. For this purpose, we utilize a publicly available EEG dataset that contains EEG signal recordings from fifteen subjects acquired using a 61-channel EEG device. We propose a method to classify four ME classes for different subjects using spectrograms of the EEG data through pre-trained deep learning (DL) models. Our proposed method of using EEG spectrograms for the classification of ME has shown significant results, where the highest average classification accuracy (for four ME classes) obtained is 87.36%, with one subject achieving the best classification accuracy of 97.03%.Clinical relevance- This research shows that movement execution of upper limbs is classified with significant accuracy by employing a spectrogram of the EEG signals and a pre-trained deep learning model which is fine-tuned for the downstream task.}, } @article {pmid38082598, year = {2023}, author = {Zhang, C and Deng, F and Li, Y and Hall, T and Goldys, E}, title = {Paper-based lateral flow assay for the point-of-care detection of neurofilament light chain.}, journal = {Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference}, volume = {2023}, number = {}, pages = {1-4}, doi = {10.1109/EMBC40787.2023.10340109}, pmid = {38082598}, issn = {2694-0604}, mesh = {Humans ; *Point-of-Care Systems ; Intermediate Filaments/metabolism ; Reproducibility of Results ; *Amyotrophic Lateral Sclerosis/diagnosis/metabolism ; Biomarkers ; }, abstract = {Neurofilament light chain (NF-L) is a protein found in neurons of the nervous system and is widely used as a biomarker for neurological disorders. However, the current methods for detecting NF-L levels are complicated, expensive, and require specialized equipment, making it challenging to implement in a point-of-care (POC) setting. In this study, we developed a gold nanoshell (AuNS)-assisted lateral flow assay (LFA) based test strip for the POC detection of NF-L at a low ng/mL level (8 ng/mL = 117.65 pM). The test strip is a simple, rapid, and cost-effective method for detecting NF-L, making it suitable for use in a POC setting for the diagnosis and treatment of various neurological disorders. With its ease of use and reliability, the paper-based LFA is a valuable tool for the diagnosis and management of neurological conditions.Clinical Relevance- The AuNS-assisted LFA test strip developed in this study offers a rapid, cost-effective, and simple method for detecting NF-L levels, making it of great interest to practicing clinicians for the diagnosis of various neurological diseases such as HIV-associated dementia (HID), Amyotrophic Lateral Sclerosis (ALS), and Creutzfeldt-Jakob disease (CJD).}, } @article {pmid38082513, year = {2023}, author = {Lluch-Galcerá, JJ and Alcoverro, C and Prat, E and Martinez-Molina, M and Bielsa, I and Quer, A and Bassas, J}, title = {[Refraktärer IgA-Pemphigus erfolgreich mit Adalimumab als Monotherapie behandelt].}, journal = {Journal der Deutschen Dermatologischen Gesellschaft = Journal of the German Society of Dermatology : JDDG}, volume = {21}, number = {12}, pages = {1560-1562}, doi = {10.1111/ddg.15232_g}, pmid = {38082513}, issn = {1610-0387}, } @article {pmid38081672, year = {2023}, author = {Xiong, S and Klesges, L and Doering, M and Pratt, RJ}, title = {Applications of implementation science frameworks, models and theories in disparities-focused cancer screening interventions: a scoping review protocol.}, journal = {BMJ open}, volume = {13}, number = {12}, pages = {e078212}, pmid = {38081672}, issn = {2044-6055}, support = {T32 CA190194/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; *Early Detection of Cancer ; Implementation Science ; *Neoplasms/diagnosis/prevention & control ; Research Design ; Scoping Reviews As Topic ; }, abstract = {BACKGROUND: Implementation science (IS) frameworks, models and theories (FMTs) have gained popularity in guiding the implementation and evaluation of evidence-based interventions (EBIs) for cancer screening. However, there are significant research gaps in understanding their applications in cancer health disparities contexts. This paper outlines a scoping review protocol designed to explore the utilisation of IS FMTs in cancer screening EBIs to inform intervention designs and adaptations.

METHODS AND ANALYSIS: This scoping review protocol adheres to Arksey and O'Malley's five-step methodological framework for conducting scoping studies. Search strategies were conducted in five bibliographic databases: Ovid MEDLINE, PubMed, Scopus, Web of Science and EMBASE. The search was run on 22 June 2023 with an English language filter and a date limit of 2001-current. Two reviewers will independently screen studies for inclusion and exclusion criteria. A third reviewer will be consulted, where appropriate at any of the review stages, to achieve consensus or resolve conflicts. Data will be collected, managed and analysed using Covidence. A narrative synthesis, based on Popay et al's methodology, will guide reporting and summarisation of results. The review will adhere to the PRISMA Extension for Scoping Reviews guidelines.

ETHICS AND DISSEMINATION: This scoping review is a novel approach for examining a growing corpus of research literature on IS FMT applications used in cancer screening EBIs. As a secondary analysis, this scoping review does not require approval from an institutional review board. We anticipate the review will produce insightful information (eg, challenges, key areas for future directions) on the applications of IS TMFs in designing, deploying and testing EBIs for populations experiencing cancer screening disparities. We will disseminate the results through journals and conferences targeting IS and cancer prevention researchers and practitioners.}, } @article {pmid38079474, year = {2024}, author = {Zibold, J and Lessard, LER and Picard, F and da Silva, LG and Zadorozhna, Y and Streichenberger, N and Belotti, E and Osseni, A and Emerit, A and Errazuriz-Cerda, E and Michel-Calemard, L and Menassa, R and Coudert, L and Wiessner, M and Stucka, R and Klopstock, T and Simonetti, F and Hutten, S and Nonaka, T and Hasegawa, M and Strom, TM and Bernard, E and Ollagnon, E and Urtizberea, A and Dormann, D and Petiot, P and Schaeffer, L and Senderek, J and Leblanc, P}, title = {The new missense G376V-TDP-43 variant induces late-onset distal myopathy but not amyotrophic lateral sclerosis.}, journal = {Brain : a journal of neurology}, volume = {147}, number = {5}, pages = {1768-1783}, pmid = {38079474}, issn = {1460-2156}, support = {//CNRS/ ; //Fondation pour la Recherche Médicale/ ; //Federal Ministry of Education and Research/ ; //German Research Foundation/ ; //Core/ ; //CLSM/ ; }, mesh = {Humans ; *Mutation, Missense/genetics ; *Amyotrophic Lateral Sclerosis/genetics/pathology ; Male ; *Distal Myopathies/genetics/pathology ; *DNA-Binding Proteins/genetics ; Female ; Middle Aged ; Aged ; Pedigree ; Muscle, Skeletal/pathology/metabolism ; }, abstract = {TAR DNA binding protein of 43 kDa (TDP-43)-positive inclusions in neurons are a hallmark of several neurodegenerative diseases including familial amyotrophic lateral sclerosis (fALS) caused by pathogenic TARDBP variants as well as more common non-Mendelian sporadic ALS (sALS). Here we report a G376V-TDP-43 missense variant in the C-terminal prion-like domain of the protein in two French families affected by an autosomal dominant myopathy but not fulfilling diagnostic criteria for ALS. Patients from both families presented with progressive weakness and atrophy of distal muscles, starting in their fifth to seventh decade. Muscle biopsies revealed a degenerative myopathy characterized by accumulation of rimmed (autophagic) vacuoles, disruption of sarcomere integrity and severe myofibrillar disorganization. The G376V variant altered a highly conserved amino acid residue and was absent in databases on human genome variation. Variant pathogenicity was supported by in silico analyses and functional studies. The G376V mutant increased the formation of cytoplasmic TDP-43 condensates in cell culture models, promoted assembly into high molecular weight oligomers and aggregates in vitro, and altered morphology of TDP-43 condensates arising from phase separation. Moreover, the variant led to the formation of cytoplasmic TDP-43 condensates in patient-derived myoblasts and induced abnormal mRNA splicing in patient muscle tissue. The identification of individuals with TDP-43-related myopathy, but not ALS, implies that TARDBP missense variants may have more pleiotropic effects than previously anticipated and support a primary role for TDP-43 in skeletal muscle pathophysiology. We propose to include TARDBP screening in the genetic work-up of patients with late-onset distal myopathy. Further research is warranted to examine the precise pathogenic mechanisms of TARDBP variants causing either a neurodegenerative or myopathic phenotype.}, } @article {pmid38078970, year = {2024}, author = {Sun, Z and Zhang, B and Peng, Y}, title = {Development of novel treatments for amyotrophic lateral sclerosis.}, journal = {Metabolic brain disease}, volume = {39}, number = {3}, pages = {467-482}, pmid = {38078970}, issn = {1573-7365}, support = {No. 82073835, and 81872855//National Natural Sciences Foundation of China/ ; No. 2021-I2M-1-054//CAMS Innovation Fund for Medical Sciences/ ; 201920200802//Disciplines construction project/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy/pathology ; *Neurodegenerative Diseases ; }, abstract = {Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease that causes paralysis whose etiology and pathogenesis have not been fully elucidated. Presently it is incurable and rapidly progressive with a survival of 2-5 years from onset, and no treatments could cure it. Therefore, it is urgent to identify which therapeutic target(s) are more promising to develop treatments that could effectively treat ALS. So far, more than 90 novel treatments for ALS patients have been registered on ClinicalTrials.gov, of which 23 are in clinical trials, 12 have been terminated and the rest suspended. This review will systematically summarize the possible targets of these novel treatments under development or failing based on published literature and information released by sponsors, so as to provide basis and support for subsequent drug research and development.}, } @article {pmid38078426, year = {2023}, author = {Handberg, C and Werlauff, U}, title = {People with neuromuscular diseases and their relatives' perspectives on challenges in everyday life and healthcare.}, journal = {Neurodegenerative disease management}, volume = {13}, number = {5}, pages = {289-302}, doi = {10.2217/nmt-2023-0008}, pmid = {38078426}, issn = {1758-2032}, mesh = {Humans ; *Delivery of Health Care ; *Neuromuscular Diseases ; }, abstract = {Objective: People with a neuromuscular disease (NMD) often experience challenges in everyday life and healthcare. Aim: To investigate experiences of and perspectives on challenges in everyday life and healthcare of people with NMDs and their relatives to gain new insights into how life-long rehabilitation can be tailored. Patients & methods: The design was qualitative using the interpretive description methodology and the Sense of Coherence theory. An ethnographic fieldwork was conducted where 45 persons with NMD and their relatives were included for interviews and participant observations. Results & conclusion: People with NMDs continually adapt to a changing functioning and balance their need for knowledge with their dependency on help when navigating the healthcare system. Structured, professionally facilitated peer support is needed.}, } @article {pmid38078079, year = {2023}, author = {Shi, J and Yu, H and Fu, Y and Wang, T and Zhang, Y and Huang, J and Li, S and Zheng, T and Ni, X and Zhao, J}, title = {Development and validation of functional kompetitive allele-specific PCR markers for herbicide resistance in Brassica napus.}, journal = {Frontiers in plant science}, volume = {14}, number = {}, pages = {1213476}, pmid = {38078079}, issn = {1664-462X}, abstract = {Effective weed control in the field is essential for maintaining favorable growing conditions and rapeseed yields. Sulfonylurea herbicides are one kind of most widely used herbicides worldwide, which control weeds by inhibiting acetolactate synthase (ALS). Molecular markers have been designed from polymorphic sites within the sequences of ALS genes, aiding marker-assisted selection in breeding herbicide-resistant rapeseed cultivars. However, most of them are not breeder friendly and have relatively limited application due to higher costs and lower throughput in the breeding projects. The aims of this study were to develop high throughput kompetitive allele-specific PCR (KASP) assays for herbicide resistance. We first cloned and sequenced BnALS1 and BnALS3 genes from susceptible cultivars and resistant 5N (als1als1/als3als3 double mutant). Sequence alignments of BnALS1 and BnALS3 genes for cultivars and 5N showed single nucleotide polymorphisms (SNPs) at positions 1676 and 1667 respectively. These two SNPs for BnALS1 and BnALS3 resulted in amino acid substitutions and were used to develop a KASP assay. These functional markers were validated in three distinct BC1F2 populations. The KASP assay developed in this study will be valuable for the high-throughput selection of elite materials with high herbicide resistance in rapeseed breeding programs.}, } @article {pmid38077951, year = {2023}, author = {Adachi, K and Miyata, K and Chida, Y and Hirose, M and Morisaki, Y and Yamanaka, K and Misawa, H}, title = {Depletion of perivascular macrophages delays ALS disease progression by ameliorating blood-spinal cord barrier impairment in SOD1[G93A] mice.}, journal = {Frontiers in cellular neuroscience}, volume = {17}, number = {}, pages = {1291673}, pmid = {38077951}, issn = {1662-5102}, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disease in which non-cell-autonomous processes have been proposed as its cause. Non-neuronal cells that constitute the environment around motor neurons are known to mediate the pathogenesis of ALS. Perivascular macrophages (PVM) are immune cells that reside between the blood vessels of the central nervous system and the brain parenchyma; PVM are components of the neurovascular unit and regulate the integrity of the blood-spinal cord barrier (BSCB). However, it is not known whether regulation of BSCB function by PVM is involved in the pathogenesis of ALS. Here, we used SOD1[G93A] mice to investigate whether PVM is involved in the pathogenesis of ALS. Immunostaining revealed that the number of PVM was increased during the disease progression of ALS in the spinal cord. We also found that both anti-inflammatory Lyve1[+] PVM and pro-inflammatory MHCII[+] PVM subtypes were increased in SOD1[G93A] mice, and that subtype heterogeneity was shifted toward MHCII[+] PVM compared to wild-type (WT) mice. Then we depleted PVM selectively and continuously in SOD1[G93A] mice by repeated injection of clodronate liposomes into the cerebrospinal fluid and assessed motor neuron number, neurological score, and survival. Results showed that PVM depletion prevented the loss of motoneurons, slowed disease progression, and prolonged survival. Further histological analysis showed that PVM depletion prevents BSCB collapse by ameliorating the reduction of extracellular matrix proteins necessary for the maintenance of barrier function. These results indicate that PVM are involved in the pathogenesis of ALS, as PVM degrades the extracellular matrix and reduces BSCB function, which may affect motor neuron loss and disease progression. Targeting PVM interventions may represent a novel ALS therapeutic strategy.}, } @article {pmid38077871, year = {2023}, author = {Methods In Medicine, CAM}, title = {Retracted: Study on the Diagnostic Value of Neuroelectrophysiological Examination in Patients with Amyotrophic Lateral Sclerosis.}, journal = {Computational and mathematical methods in medicine}, volume = {2023}, number = {}, pages = {9858143}, pmid = {38077871}, issn = {1748-6718}, abstract = {[This retracts the article DOI: 10.1155/2022/3907751.].}, } @article {pmid38077837, year = {2023}, author = {Bekdik, P and Baslo, MB}, title = {Investigation of Ongoing Denervation and Reinnervation in Amyotrophic Lateral Sclerosis by Using Concentric Needle Electrode with Single Fiber Electromyography Method.}, journal = {Noro psikiyatri arsivi}, volume = {60}, number = {4}, pages = {298-303}, pmid = {38077837}, issn = {1300-0667}, abstract = {INTRODUCTION: The aim of this study is to demonstrate the conduction disturbance at the neuromuscular junction in a cranial muscle by measuring jitter with a concentric needle (CN) electrode in the diagnosis of Amyotrophic Lateral Sclerosis (ALS) and to investigate the utility of evaluating the peak number as an ongoing reinnervation marker.

METHOD: Twelve patients diagnosed with ALS were included in this study. Single fiber electromyography (SFEMG) was performed using a CN electrode during the voluntary contraction of the right extensor digitorum communis (EDC) and left frontalis muscles.

RESULTS: In SFEMG from the right EDC muscle, the mean jitter value was high in all of them. The average jitter calculated in EDC muscles was 57.76±24.17 μs. The mean jitter value in the frontal muscles was 28.91±10.21 μs. In all patients, the number of CN electrode peaks was more than 4 in the EDC muscle and above 4 in 91.67% of the frontal muscle.

CONCLUSION: Detection of high jitter in SFEMG examination indicates that the examined muscle undergoes a denervation-reinnervation process in the case of increased peak number values. When such a determination is made in the extremity muscles, it becomes important for the diagnosis of ALS.}, } @article {pmid38077003, year = {2023}, author = {Zhou, Z and Kim, J and Huang, AY and Nolan, M and Park, J and Doan, R and Shin, T and Miller, MB and Chhouk, B and Morillo, K and Yeh, RC and Kenny, C and Neil, JE and Lee, CZ and Ohkubo, T and Ravits, J and Ansorge, O and Ostrow, LW and Lagier-Tourenne, C and Lee, EA and Walsh, CA}, title = {Somatic Mosaicism in Amyotrophic Lateral Sclerosis and Frontotemporal Dementia Reveals Widespread Degeneration from Focal Mutations.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {38077003}, issn = {2692-8205}, support = {R56 AG079857/AG/NIA NIH HHS/United States ; DP2 AG072437/AG/NIA NIH HHS/United States ; K01 AG051791/AG/NIA NIH HHS/United States ; R01 AG070921/AG/NIA NIH HHS/United States ; R01 NS032457/NS/NINDS NIH HHS/United States ; DP2 AG086138/AG/NIA NIH HHS/United States ; R01 AG082346/AG/NIA NIH HHS/United States ; K08 AG065502/AG/NIA NIH HHS/United States ; }, abstract = {Although mutations in dozens of genes have been implicated in familial forms of amyotrophic lateral sclerosis (fALS) and frontotemporal degeneration (fFTD), most cases of these conditions are sporadic (sALS and sFTD), with no family history, and their etiology remains obscure. We tested the hypothesis that somatic mosaic mutations, present in some but not all cells, might contribute in these cases, by performing ultra-deep, targeted sequencing of 88 genes associated with neurodegenerative diseases in postmortem brain and spinal cord samples from 404 individuals with sALS or sFTD and 144 controls. Known pathogenic germline mutations were found in 20.6% of ALS, and 26.5% of FTD cases. Predicted pathogenic somatic mutations in ALS/FTD genes were observed in 2.7% of sALS and sFTD cases that did not carry known pathogenic or novel germline mutations. Somatic mutations showed low variant allele fraction (typically <2%) and were often restricted to the region of initial discovery, preventing detection through genetic screening in peripheral tissues. Damaging somatic mutations were preferentially enriched in primary motor cortex of sALS and prefrontal cortex of sFTD, mirroring regions most severely affected in each disease. Somatic mutation analysis of bulk RNA-seq data from brain and spinal cord from an additional 143 sALS cases and 23 controls confirmed an overall enrichment of somatic mutations in sALS. Two adult sALS cases were identified bearing pathogenic somatic mutations in DYNC1H1 and LMNA, two genes associated with pediatric motor neuron degeneration. Our study suggests that somatic mutations in fALS/fFTD genes, and in genes associated with more severe diseases in the germline state, contribute to sALS and sFTD, and that mosaic mutations in a small fraction of cells in focal regions of the nervous system can ultimately result in widespread degeneration.}, } @article {pmid38076820, year = {2024}, author = {Worthy, AE and Anderson, JT and Lane, AR and Gomez-Perez, L and Wang, AA and Griffith, RW and Rivard, AF and Bikoff, JB and Alvarez, FJ}, title = {Spinal V1 inhibitory interneuron clades differ in birthdate, projections to motoneurons, and heterogeneity.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2023.11.29.569270}, pmid = {38076820}, issn = {2692-8205}, support = {R01 NS047357/NS/NINDS NIH HHS/United States ; }, abstract = {UNLABELLED: Spinal cord interneurons play critical roles shaping motor output, but their precise identity and connectivity remain unclear. Focusing on the V1 interneuron cardinal class we defined four major V1 subsets according to neurogenesis timing, genetic lineage-tracing, synaptic output to motoneurons, and synaptic inputs from muscle afferents. Birthdate delineates two early born (Renshaw and Pou6f2) and two late born (Foxp2 and Sp8) V1 clades, showing that sequential neurogenesis produces different V1 subsets. Early born Renshaw cells and late born Foxp2-V1 interneurons are tightly coupled to motoneurons, while early born Pou6f2-V1 and late born Sp8-V1 interneurons are not, indicating that timing of neurogenesis does not correlate with motoneuron targeting. V1 clades also differ in cell numbers and diversity. Lineage labeling shows that the Foxp2-V1 clade contains over half of all V1 interneurons, provides the largest inhibitory input to motoneuron cell bodies and includes subgroups that differ in birthdate, location, and proprioceptive input. Notably, one Foxp2-V1 subgroup, defined by postnatal Otp expression is positioned near the lateral motor column and receives substantial input from proprioceptors, consistent with an involvement in reciprocal inhibitory pathways. Combined tracing of ankle flexor sensory afferents and interneurons monosynaptically connected to ankle extensors confirmed placement of Foxp2-V1 interneurons in reciprocal inhibitory pathways. Our results validate previously proposed V1 clades as unique functional subtypes that differ in circuit placement, with Foxp2-V1 cells forming the most heterogeneous subgroup. We discuss how V1 organizational diversity enables understanding of their roles in motor control, with implications for their diverse ontogenetic and phylogenetic origins.

SIGNIFICANCE STATEMENT: The complexity of spinal interneuron diversity and circuit organization represents a challenge to understand neural control of movement in normal adults as well as during motor development and in disease. Inhibitory interneurons are a core element of these spinal circuits. V1 interneurons comprise the largest group of inhibitory interneurons in the ventral horn, and their organization remains unclear. Here we present a comprehensive examination of V1 subtypes according to neurogenesis, placement in spinal motor circuits, and motoneuron synaptic targeting. V1 diversity increases during evolution from axial-swimming fishes to limb-based mammalian terrestrial locomotion. This increased diversity is reflected in the size and heterogeneity of the Foxp2-V1 clade, a group closely associated with limb motor pools. We show that Foxp2-V1 interneurons establish the densest direct inhibitory input to motoneurons, especially on cell bodies. These findings are particularly significant because recent studies have shown that motor neurodegenerative diseases like amyotrophic lateral sclerosis (ALS) affect inhibitory V1 synapses on motoneuron cell bodies and Foxp2-V1 interneurons themselves in the earliest stages of pathology.}, } @article {pmid38073637, year = {2023}, author = {Mitsi, E and Christodoulou, CC and Nicolaou, P and Christodoulou, K and Zamba-Papanicolaou, E}, title = {The influence of environmental risk factors in the development of ALS in the Mediterranean Island of Cyprus.}, journal = {Frontiers in neurology}, volume = {14}, number = {}, pages = {1264743}, pmid = {38073637}, issn = {1664-2295}, abstract = {INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a devastating, uniformly lethal degenerative disease of motor neurons, presenting with relentlessly progressive muscle atrophy and weakness. The etiology of ALS remains unexplained for over 85% of all cases, suggesting that besides the genetic basis of the disease, various environmental factors are implicated in the pathogenesis of ALS. This study aimed to investigate the contribution of known environmental risk factors of ALS in the Cypriot population.

METHODS: We conducted a case-control study with a total of 56 ALS cases and 56 healthy gender/age-matched controls of Cypriot nationality. Demographic, lifestyle characteristics, medical conditions, and environmental exposures were collected through the use of a detailed questionnaire. Statistical analyses using the R programming language examined the association between the above environmental factors and ALS.

RESULTS: A chi-square test analysis revealed a statistically significant (p = 0.000461) difference in smoking status between the two groups. In addition, univariate logistic regression analysis showed a statistically significant association between ALS cases for head trauma/injury (p = 0.0398) and exposure to chemicals (p = 0.00128), compared to controls.

CONCLUSION: This case-control investigation has shed some light on the epidemiological data of ALS in Cyprus, by identifying environmental determinants of ALS, such as smoking, head trauma, and chemical exposure, in the Cypriot population.}, } @article {pmid38072540, year = {2023}, author = {Yu, H and Guo, X and Peng, L and Li, X and Chen, J and Cui, H}, title = {Target gene mutations endowed cross-resistance to acetolactate synthase-inhibiting herbicides in wild Brassica juncea.}, journal = {Pesticide biochemistry and physiology}, volume = {197}, number = {}, pages = {105683}, doi = {10.1016/j.pestbp.2023.105683}, pmid = {38072540}, issn = {1095-9939}, mesh = {Amino Acids ; Mustard Plant/genetics/metabolism ; *Herbicides/pharmacology ; *Acetolactate Synthase/metabolism ; Herbicide Resistance/genetics ; Sodium ; Mutation ; Amyotrophic Lateral Sclerosis ; }, abstract = {Wild Brassica juncea is a troublesome weed that infests wheat fields in China. Two suspected wild B. juncea populations (19-5 and 19-6) resistant to acetolactate synthase (ALS) inhibitors were collected from wheat fields in China. To clarify their resistance profiles and resistance mechanism, the resistance levels of populations 19-5 and 19-6 to ALS-inhibiting herbicides and their underlying target-site resistance mechanism were investigated. The results showed that the 19-5 population exhibited resistance to tribenuron-methyl, pyrithiobac‑sodium and florasulam, while the 19-6 population was resistant to tribenuron-methyl, pyrithiobac‑sodium, imazethapyr and florasulam. Using the homologous cloning method, two ALS genes were identified in wild B. juncea, with one gene (ALS1) encoding 652 amino acids and the other (ALS2) encoding 655 amino acids. Pro-197-Arg mutation on ALS2 and Trp-574-Leu mutation on ALS1, together with the combination of these two mutations in a single plant, were observed in both 19-5 and 19-6 populations. ALS2 enzymes carrying the Pro-197-Arg mutation were cross-resistant to tribenuron-methyl, pyrithiobac‑sodium, imazerthapyr and florasulam, with resistance index (RI) values of 6.23, 32.81, 7.97 and 1162.50, respectively. Similarly, ALS1 enzymes with Trp-574-leu substitutions also displayed high resistance to these four herbicides (RI values ranging from 132.61 to 3375.00). In addition, the combination of Pro-197-Arg (ALS2) and Trp-574-Leu (ALS1) mutations increased the resistance level of the ALS enzyme to ALS inhibitors, with its RI values 3.83-214.19, 6.88-37.34, 1.91-31.82 and 2.03-5.90-fold higher than a single mutation for tribenuron-methyl, pyrithiobac‑sodium, imazerthapyr and florasulam, respectively. Collectively, Pro-197-Arg mutation on ALS2, Trp-574-Leu mutation on ALS1 and the combination of Pro-197-Arg (ALS2) and Trp-574-Leu (ALS1) mutations in wild B. juncea could endow broad-spectrum resistance to ALS inhibitors, which might provide guides for establishing effective strategies to prevent or delay such resistance evolution in this weed.}, } @article {pmid38072525, year = {2023}, author = {Han, Y and Sun, Y and Ma, H and Wang, R and Lan, Y and Gao, H and Huang, Z}, title = {Target-site and non-target-site based resistance to clodinafop-propargyl in wild oats (Avena fatua L.).}, journal = {Pesticide biochemistry and physiology}, volume = {197}, number = {}, pages = {105650}, doi = {10.1016/j.pestbp.2023.105650}, pmid = {38072525}, issn = {1095-9939}, mesh = {*Avena/genetics ; Poaceae/genetics ; Plant Proteins/genetics/metabolism ; Herbicide Resistance/genetics ; *Herbicides/pharmacology ; Acetyl-CoA Carboxylase/genetics/metabolism ; Mutation ; }, abstract = {Wild oat (Avena fatua L.) is a common and problematic weed in wheat fields in China. In recent years, farmers found it increasingly difficult to control A. fatua using acetyl-CoA carboxylase (ACCase)-inhibiting herbicides. The purpose of this study was to identify the molecular basis of clodinafop-propargyl resistance in A. fatua. In comparison to the S1496 population, whole dose response studies revealed that the R1623 and R1625 populations were 71.71- and 67.76-fold resistant to clodinafop-propargyl, respectively. The two resistant A. fatua populations displayed high resistance to fenoxaprop-p-ethyl (APP) and low resistance to clethodim (CHD) and pinoxaden (PPZ), but they were still sensitive to the ALS inhibitors mesosulfuron-methyl and pyroxsulam. An Ile-2041-Asn mutation was identified in both resistant individual plants. The copy number and relative expression of the ACCase gene in the resistant population were not significantly different from those in the S1496 population. Under the application of 2160 g ai ha [-1] of clodinafop-propargyl, the fresh weight of the R1623 population was reduced to 74.9%; however, pretreatment with the application of the cytochrome P450 inhibitor malathion and the GST inhibitor NBD-Cl reduced the fresh weight to 50.91% and 47.16%, respectively, which proved the presence of metabolic resistance. This is the first report of an Ile-2041-Asn mutation and probable metabolic resistance in A. fatua, resulting in resistance to clodinafop-propargyl.}, } @article {pmid38072442, year = {2024}, author = {Matsushita, M and Nakamura, Y and Hosokawa, T and Takahashi, Y and Mizusawa, H and Arawaka, S}, title = {[Spinocerebellar ataxia 2 develop lower motor neuron involvement as an initial symptom: a case report].}, journal = {Rinsho shinkeigaku = Clinical neurology}, volume = {64}, number = {1}, pages = {28-32}, doi = {10.5692/clinicalneurol.cn-001910}, pmid = {38072442}, issn = {1882-0654}, mesh = {Male ; Humans ; Adult ; *Trinucleotide Repeat Expansion ; *Spinocerebellar Ataxias/diagnosis/genetics ; Ataxia ; Motor Neurons ; Atrophy ; }, abstract = {A 36-year-old man has developed weakness of left thumb and atrophy of left thenar muscle and left first dorsal interosseous muscle without sensory disturbance for a year. A nerve conduction study revealed decreases in the amplitude of compound muscle action potentials and occurrence of F-waves on left medial nerve. Needle electromyography examination revealed positive sharp waves and later recruited motor units on left abductor pollicis brevis muscle. Brain MRI showed atrophy of bilateral cerebellar hemisphere. His grandmother and his two uncles have been diagnosed as spinocerebellar degeneration. After discharge, he developed bilateral lower limb ataxia. Genetic analysis showed heterozygous CAG repeat expansion (19/39) in ATXN2 gene, being diagnosed as spinocerebellar ataxia 2 (SCA2). A previous report has shown that motor neuron involvement is recognized as part of SCA2 in the same pedigree with full CAG repeat expansions in ATXN2 gene. We here report the patient with lower motor neuron involvement as an initial symptom of SCA2.}, } @article {pmid38072117, year = {2024}, author = {Alaoui Mansouri, M and Kharbach, M and Bouklouze, A}, title = {Current Applications of Multivariate Curve Resolution-Alternating Least Squares (MCR-ALS) in Pharmaceutical Analysis: Review.}, journal = {Journal of pharmaceutical sciences}, volume = {113}, number = {4}, pages = {856-865}, doi = {10.1016/j.xphs.2023.12.004}, pmid = {38072117}, issn = {1520-6017}, mesh = {Least-Squares Analysis ; *Biopharmaceutics ; Pharmaceutical Preparations ; Multivariate Analysis ; }, abstract = {The present review encompasses various applications of multivariate curve resolution- alternating least squares (MCR-ALS) as a promising data handling, which is issued by analytical techniques in pharmaceutics. It involves different sections starting from a concise theory of MCR-ALS and four detailed applications in drugs analysis. Dissolution, stability, polymorphism, and quantification are the main four detailed applications. The data generated by analytical techniques associated with MCR-ALS deals accurately with different challenges compared to other chemometric tools. For each reviewed purpose, it was explained how MCR-ALS was applied and detailed information was given. Different approaches were introduced to overcome challenges that limit the use of MCR-ALS efficiently in pharmaceutical mixture were also discussed.}, } @article {pmid38072051, year = {2024}, author = {Lu, J and Ge, P and Sawaya, MR and Hughes, MP and Boyer, DR and Cao, Q and Abskharon, R and Cascio, D and Tayeb-Fligelman, E and Eisenberg, DS}, title = {Cryo-EM structures of the D290V mutant of the hnRNPA2 low-complexity domain suggests how D290V affects phase separation and aggregation.}, journal = {The Journal of biological chemistry}, volume = {300}, number = {2}, pages = {105531}, pmid = {38072051}, issn = {1083-351X}, support = {RF1 AG065407/AG/NIA NIH HHS/United States ; R01 AG070895/AG/NIA NIH HHS/United States ; R01 AG048120/AG/NIA NIH HHS/United States ; }, mesh = {Humans ; *Cryoelectron Microscopy ; Phase Separation ; Protein Domains ; Mutation ; Hydrogen-Ion Concentration ; *Models, Molecular ; Protein Stability ; Protein Structure, Tertiary ; *Heterogeneous-Nuclear Ribonucleoprotein Group A-B/chemistry/metabolism ; }, abstract = {Heterogeneous nuclear ribonucleoprotein A2 (hnRNPA2) is a human ribonucleoprotein that transports RNA to designated locations for translation via its ability to phase separate. Its mutated form, D290V, is implicated in multisystem proteinopathy known to afflict two families, mainly with myopathy and Paget's disease of bone. Here, we investigate this mutant form of hnRNPA2 by determining cryo-EM structures of the recombinant D290V low complexity domain. We find that the mutant form of hnRNPA2 differs from the WT fibrils in four ways. In contrast to the WT fibrils, the PY-nuclear localization signals in the fibril cores of all three mutant polymorphs are less accessible to chaperones. Also, the mutant fibrils are more stable than WT fibrils as judged by phase separation, thermal stability, and energetic calculations. Similar to other pathogenic amyloids, the mutant fibrils are polymorphic. Thus, these structures offer evidence to explain how a D-to-V missense mutation diverts the assembly of reversible, functional amyloid-like fibrils into the assembly of pathogenic amyloid, and may shed light on analogous conversions occurring in other ribonucleoproteins that lead to neurological diseases such as amyotrophic lateral sclerosis and frontotemporal dementia.}, } @article {pmid38071852, year = {2024}, author = {Musso, G and Blasi, L and Mion, MM and Fortuna, A and Sabbatini, D and Zaninotto, M and Bello, L and Pegoraro, E and Basso, D and Plebani, M and Sorarù, G}, title = {Troponin T in spinal and bulbar muscular atrophy (SBMA).}, journal = {Journal of the neurological sciences}, volume = {456}, number = {}, pages = {122816}, doi = {10.1016/j.jns.2023.122816}, pmid = {38071852}, issn = {1878-5883}, mesh = {Adult ; Humans ; Troponin T ; *Bulbo-Spinal Atrophy, X-Linked ; *Muscular Atrophy, Spinal/diagnosis ; Biomarkers ; *Neuromuscular Diseases ; *Amyotrophic Lateral Sclerosis ; *Spinal Muscular Atrophies of Childhood ; }, abstract = {Serum biomarkers that might detect clinical progression are currently lacking for Spinal and bulbar muscular atrophy (SBMA), thus limiting the effectiveness of possible future pharmacological trials. Elevation of cardiac troponin T (cTnT) unrelated to myocardial damage in a motor neuron (MN) disease as amyotrophic lateral sclerosis (ALS) was associated to disease severity. We enrolled 47 SBMA patients and 5 Spinal muscular atrophy (SMA) type 3 adult patients as control group; each SBMA patient was evaluated at baseline and at one-year follow-up visit. Demographic and clinical data including functional scores (SBMAFRS) were collected; serum was collected as standard of care and tested for cardiac troponins. Levels of cTnT but not cTnI were increased in SBMA with respect to reference values; unlike other neuromuscular diseases, SMA patients had overall normal cTnT values. Median cTnT concentrations did not change after one year and values were correlated to motor function, particularly with lower limb subdomain, at baseline only. Variations of cTnT and of SBMAFRS were unrelated. The cautiously promising results of cTnT as potential biomarker should undergo a more extensive clinical validation, including studies with longer follow-up period. When evaluating SBMA patients for a potential cardiac damage cTnI testing should be coupled or preferred to cTnT.}, } @article {pmid38070961, year = {2023}, author = {Krall, JTW and Chakravartty, A and Caress, JB and Files, DC}, title = {Identification and Management of Acute Neuromuscular Respiratory Failure in the ICU.}, journal = {Chest}, volume = {164}, number = {6}, pages = {1454-1461}, doi = {10.1016/j.chest.2023.09.009}, pmid = {38070961}, issn = {1931-3543}, mesh = {Humans ; *Neuromuscular Diseases/complications/diagnosis/therapy ; *Respiratory Insufficiency/diagnosis/etiology/therapy ; Prognosis ; Intensive Care Units ; }, abstract = {Respiratory failure is a common and potentially life-threatening complication of neuromuscular diseases. Prompt recognition and accurate diagnosis of new or worsening chronic neuromuscular disease have important clinical management and prognostic implications. In this article, we present an approach to the acute presentation of undifferentiated neuromuscular respiratory failure in the ICU and guidance for determination and respiratory management of the underlying disorder.}, } @article {pmid38070417, year = {2024}, author = {Ur Rahman, S and Han, JC and Ahmad, M and Ashraf, MN and Khaliq, MA and Yousaf, M and Wang, Y and Yasin, G and Nawaz, MF and Khan, KA and Du, Z}, title = {Aluminum phytotoxicity in acidic environments: A comprehensive review of plant tolerance and adaptation strategies.}, journal = {Ecotoxicology and environmental safety}, volume = {269}, number = {}, pages = {115791}, doi = {10.1016/j.ecoenv.2023.115791}, pmid = {38070417}, issn = {1090-2414}, mesh = {*Aluminum/toxicity/metabolism ; Malates/metabolism ; Plant Breeding ; Plants/metabolism ; *Alkaloids/pharmacology ; Organic Chemicals/metabolism ; Soil/chemistry ; Plant Roots/metabolism ; Gene Expression Regulation, Plant ; }, abstract = {Aluminum (Al), a non-essential metal for plant growth, exerts significant phytotoxic effects, particularly on root growth. Anthropogenic activities would intensify Al's toxic effects by releasing Al[3+] into the soil solution, especially in acidic soils with a pH lower than 5.5 and rich mineral content. The severity of Al-induced phytotoxicity varies based on factors such as Al concentration, ionic form, plant species, and growth stages. Al toxicity leads to inhibited root and shoot growth, reduced plant biomass, disrupted water uptake causing nutritional imbalance, and adverse alterations in physiological, biochemical, and molecular processes. These effects collectively lead to diminished plant yield and quality, along with reduced soil fertility. Plants employ various mechanisms to counter Al toxicity under stress conditions, including sequestering Al in vacuoles, exuding organic acids (OAs) like citrate, oxalate, and malate from root tip cells to form Al-complexes, activating antioxidative enzymes, and overexpressing Al-stress regulatory genes. Recent advancements focus on enhancing the exudation of OAs to prevent Al from entering the plant, and developing Al-tolerant varieties. Gene transporter families, such as ATP-Binding Cassette (ABC), Aluminum-activated Malate Transporter (ALMT), Natural resistance-associated macrophage protein (Nramp), Multidrug and Toxic compounds Extrusion (MATE), and aquaporin, play a crucial role in regulating Al toxicity. This comprehensive review examined recent progress in understanding the cytotoxic impact of Al on plants at the cellular and molecular levels. Diverse strategies developed by both plants and scientists to mitigate Al-induced phytotoxicity were discussed. Furthermore, the review explored recent genomic developments, identifying candidate genes responsible for OAs exudation, and delved into genome-mediated breeding initiatives, isolating transgenic and advanced breeding lines to cultivate Al-tolerant plants.}, } @article {pmid38069659, year = {2024}, author = {Sommers-Spijkerman, M and Stukker, A and Kavanaugh, MS and Ketelaar, M and Visser-Meily, JMA and Beelen, A}, title = {What, how and when do families communicate about ALS? A qualitative exploration of parents' and children's perceptions.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {25}, number = {3-4}, pages = {256-263}, doi = {10.1080/21678421.2023.2290738}, pmid = {38069659}, issn = {2167-9223}, mesh = {Child ; Humans ; Adolescent ; Young Adult ; Adult ; *Amyotrophic Lateral Sclerosis/diagnosis/genetics ; Parents ; Communication ; Qualitative Research ; }, abstract = {Objectives: In families with a parent diagnosed with amyotrophic lateral sclerosis (ALS), children's adaptation depends among others on how their parents communicate with them about the disease and its trajectory. The aim of this study was to explore parents' and children's perceptions of ALS-related family communication. Methods: A qualitative analysis using a conventional content analysis approach was applied to interview data previously collected from 21 parents (8 with ALS) and 15 children (age 13-23 years) about their experiences living with ALS. Results: Three themes emerged from the interviews: communication topics, styles and timing. Communication topics include facts about disease and prognosis, feelings, care and equipment, and the end. Although most parents perceived the familial communication style concerning ALS as open, the interviews revealed that both parents and children sometimes avoid interactions about ALS, because they do not know what to say or how to open the dialogue, are afraid to burden other family members, or are unwilling to discuss. Communication timing is directed by changes in the disease trajectory and/or questions of children. A family-level analysis showed that ALS-related family communication is sometimes perceived differently by parents and children. Conclusions: The study provides a better understanding of what, how and when parents and children in families living with ALS communicate about the disease. Most families opened the dialogue about ALS yet encountered challenges which may hamper good familial communication. Through addressing those challenges, healthcare professionals may facilitate better communication and adaptation in families with a parent with ALS.}, } @article {pmid38069599, year = {2024}, author = {Hansen, G and Burton-MacLeod, S and Schellenberg, KL}, title = {ALS Health care provider wellness.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {25}, number = {3-4}, pages = {299-307}, doi = {10.1080/21678421.2023.2291710}, pmid = {38069599}, issn = {2167-9223}, mesh = {Humans ; Female ; *Amyotrophic Lateral Sclerosis/epidemiology ; Pandemics ; Canada/epidemiology ; Health Personnel/psychology ; *Physicians/psychology ; *Burnout, Professional/epidemiology/psychology ; Surveys and Questionnaires ; }, abstract = {BACKGROUND: Interest in health care provider (HCP) wellness and burnout is increasing; however, minimal literature explores HCP wellness in the context of Amyotrophic Lateral Sclerosis (ALS) care.

OBJECTIVES: We sought to determine rates of burnout and resiliency, as well as challenges and rewards in the provision of ALS care.

METHODS: A survey link was sent to physicians at all Canadian ALS centers for distribution to ALS HCPs in their network. The survey included demographics questions, and validated measures for resiliency and burnout; the Brief Resilient Coping Scale (BRCS) and the Single Item Burnout Score (SIBS). Participants were asked to describe challenges and rewards of ALS care, impact of COVID-19 pandemic, and how their workplace could better support them.

RESULTS: There were 85 respondents across multiple disciplines. The rate of burnout was 47%. Burnout for female respondents was significantly higher (p = 0.007), but not for age, role, or years in ALS clinic. Most participants were medium resilient copers n = 48 (56.5%), but resiliency was not related to burnout. Challenges included feeling helpless while patients relentlessly progressed to death, and emotionally charged interactions. Participants found fulfillment in providing care, and through relationships with patients and colleagues. There was a strongly expressed desire for increased resources, team building/debriefing, and formal training in emotional exhaustion and burnout.

CONCLUSIONS: The high rate of burnout and challenges of ALS care highlight the need for additional resources, team-building, and formal education around wellness.}, } @article {pmid38069329, year = {2023}, author = {Kim, H and Kim, GS and Hyun, SH and Kim, E}, title = {Advancements in 2D and 3D In Vitro Models for Studying Neuromuscular Diseases.}, journal = {International journal of molecular sciences}, volume = {24}, number = {23}, pages = {}, pmid = {38069329}, issn = {1422-0067}, support = {NRF-2021R1C1C2007132//National Research Foundation of Korea/ ; }, mesh = {Humans ; *Neuromuscular Diseases ; Muscle, Skeletal ; Neuromuscular Junction ; Motor Neurons ; Organoids ; }, abstract = {Neuromuscular diseases (NMDs) are a genetically or clinically heterogeneous group of diseases that involve injury or dysfunction of neuromuscular tissue components, including peripheral motor neurons, skeletal muscles, and neuromuscular junctions. To study NMDs and develop potential therapies, remarkable progress has been made in generating in vitro neuromuscular models using engineering approaches to recapitulate the complex physical and biochemical microenvironments of 3D human neuromuscular tissues. In this review, we discuss recent studies focusing on the development of in vitro co-culture models of human motor neurons and skeletal muscles, with the pros and cons of each approach. Furthermore, we explain how neuromuscular in vitro models recapitulate certain aspects of specific NMDs, including amyotrophic lateral sclerosis and muscular dystrophy. Research on neuromuscular organoids (NMO) will continue to co-develop to better mimic tissues in vivo and will provide a better understanding of the development of the neuromuscular tissue, mechanisms of NMD action, and tools applicable to preclinical studies, including drug screening and toxicity tests.}, } @article {pmid38069154, year = {2023}, author = {Belosludtseva, NV and Matveeva, LA and Belosludtsev, KN}, title = {Mitochondrial Dyshomeostasis as an Early Hallmark and a Therapeutic Target in Amyotrophic Lateral Sclerosis.}, journal = {International journal of molecular sciences}, volume = {24}, number = {23}, pages = {}, pmid = {38069154}, issn = {1422-0067}, support = {23-25-00286//Russian Science Foundation/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/therapy/metabolism ; Mitochondria/metabolism ; Motor Neurons/metabolism ; Energy Metabolism ; Disease Progression ; Superoxide Dismutase-1/metabolism ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal multisystem disease characterized by progressive death of motor neurons, loss of muscle mass, and impaired energy metabolism. More than 40 genes are now known to be associated with ALS, which together account for the majority of familial forms of ALS and only 10% of sporadic ALS cases. To date, there is no consensus on the pathogenesis of ALS, which makes it difficult to develop effective therapy. Accumulating evidence indicates that mitochondria, which play an important role in cellular homeostasis, are the earliest targets in ALS, and abnormalities in their structure and functions contribute to the development of bioenergetic stress and disease progression. Mitochondria are known to be highly dynamic organelles, and their stability is maintained through a number of key regulatory pathways. Mitochondrial homeostasis is dynamically regulated via mitochondrial biogenesis, clearance, fission/fusion, and trafficking; however, the processes providing "quality control" and distribution of the organelles are prone to dysregulation in ALS. Here, we systematically summarized changes in mitochondrial turnover, dynamics, calcium homeostasis, and alterations in mitochondrial transport and functions to provide in-depth insights into disease progression pathways, which may have a significant impact on current symptomatic therapies and personalized treatment programs for patients with ALS.}, } @article {pmid38068696, year = {2023}, author = {Sun, J and Yu, X and Xu, H and Yang, Y and Liu, M and Zhang, Y and Lu, Y and Tang, W}, title = {Post-Emergence Water-Dispersal Application Provides Equal Herbicidal Activity against Echinochloa crus-galli and Rice Safety as Foliar Spraying of Penoxsulam.}, journal = {Plants (Basel, Switzerland)}, volume = {12}, number = {23}, pages = {}, pmid = {38068696}, issn = {2223-7747}, support = {LGN21C140003//Zhejiang Provincial Natural Science Foundation/ ; 32071508//National Natural Science Foundation of China/ ; CARS-01//the China Agriculture Research System/ ; }, abstract = {Penoxsulam is an acetolactate synthase (ALS)-inhibiting herbicide usually applied by post-emergence foliar spraying (PFS) for the control of Echinochloa crus-galli and numerous annual weeds in paddy fields. Herbicides applied by foliar spraying can have negative impacts on the environment, ecosystems, and human health. In this study, the response of E. crus-galli and rice to the PFS and post-emergence water-dispersal (PWD) applications of penoxsulam, and the differences in the detoxification displayed by them between the two treatment methods were compared. The results showed that the PWD application of penoxsulam provides a similar control efficacy against E. crus-galli as PFS at the 1-, 3-, and 5-leaf stages. Meanwhile, the PWD application had a higher safety for the rice. After being treated with 30 g a.i. ha[-1] penoxsulam, residues were not detected in the rice treated by the PWD application method, whereas, with the PFS treatment, there was 59.0 µg/kg penoxsulam remaining. With the PFS application, there were many more residues of penoxsulam in the E. crus-galli than with the PWD method; the amount of residues was 32-fold higher 12 h after treatment. The in vitro enzyme activity assays revealed that the activities of ALS, glutathione-S-transferase (GST), and cytochrome P450 monooxygenases (P450) were increased in the PWD treatments, and were 1.5-, 1.3-, and 2.3-fold higher than with PFS 72 h after treatment. The real-time quantitative PCR (qRT-PCR) revealed that the GST1 and P450 genes, CYP81A14, CYP81A12, CYP81A18, and CYP81A21 were upregulated with the PWD application versus PFS in the E. crus-galli. In summary, these results demonstrate that the herbicidal activity was not affected by the upregulation of target and metabolic enzyme activities with the PWD application of penoxsulam. This research could contribute to application strategies reducing the risk of rice injury and environmental impacts by using water-dispersal formulations of penoxsulam.}, } @article {pmid38068637, year = {2023}, author = {Roth, IS and Singer, A and Yadid, I and Sibony, M and Peleg, Z and Rubin, B}, title = {Do Traits Travel? Multiple-Herbicide-Resistant A. tuberculatus, an Alien Weed Species in Israel.}, journal = {Plants (Basel, Switzerland)}, volume = {12}, number = {23}, pages = {}, pmid = {38068637}, issn = {2223-7747}, support = {3011002657//Israel Cotton Board/ ; 811-0210-98//The Chief Scientist Fund, Ministry of Agriculture, Israel/ ; }, abstract = {Amaranthus tuberculatus is the most common weed in soybean and corn in the USA and Canada. In Israel, it has been a minor riverbank weed. However, in recent years, growing densities of this plant have been observed in field crops, orchards, and roadsides. Between 2017 and 2022, we surveyed the distribution of A. tuberculatus and collected seeds for further study. We identified three main distribution zones in Israel: the Jezreel Valley, Hula Valley, and Coastal Plain. Most of the populations were found near water sources, fishponds, barns, dairies, or bird-feeding sites, suggesting the involvement of imported grain in introducing A. tuberculatus to Israel. Populations were screened for their responses to various post-emergence herbicides (i.e., ALS, EPSPS, PPO, HPPD, and PSII inhibitors). Several populations from the Jezreel Valley were found to be putatively resistant to ALS, EPSPS, and PPO inhibitors. The responses of those populations to trifloxysulfuron, glyphosate, and carfentrazone-ethyl were also studied. A single ALS-, EPSPS- and PPO-resistant plant was vegetatively propagated to create a clonal population, which was treated with foramsulfuron, glyphosate, and carfentrazone-ethyl. No resistance to PSII or HPPD inhibitors was observed, but resistance to herbicides that inhibit ALS, EPSPS, and PPO was observed. A clonal propagation assay revealed the existence of a population that was resistant to ALS, EPSPS, and PPO inhibitors. Since the local A. tuberculatus populations have not been exposed to herbicide selection pressure, these traits probably reached Israel through seed-mediated gene flow via imported grain.}, } @article {pmid38067180, year = {2023}, author = {Stella, R and Bonadio, RS and Cagnin, S and Andreotti, R and Massimino, ML and Bertoli, A and Peggion, C}, title = {Secreted Metabolome of ALS-Related hSOD1(G93A) Primary Cultures of Myocytes and Implications for Myogenesis.}, journal = {Cells}, volume = {12}, number = {23}, pages = {}, pmid = {38067180}, issn = {2073-4409}, support = {BIRD 202151/20//University of Padova/ ; DOR2331994/2//University of Padova/ ; 2016-1006//The Cariplo Foundation/ ; }, mesh = {Mice ; Humans ; Animals ; *Amyotrophic Lateral Sclerosis/metabolism ; Motor Neurons/pathology ; Mice, Transgenic ; Superoxide Dismutase-1/metabolism ; *Motor Neuron Disease/metabolism ; Muscle Cells/metabolism ; Metabolome ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a motor neuron (MN) disease associated with progressive muscle atrophy, paralysis, and eventually death. Growing evidence demonstrates that the pathological process leading to ALS is the result of multiple altered mechanisms occurring not only in MNs but also in other cell types inside and outside the central nervous system. In this context, the involvement of skeletal muscle has been the subject of a few studies on patients and ALS animal models. In this work, by using primary myocytes derived from the ALS transgenic hSOD1(G93A) mouse model, we observed that the myogenic capability of such cells was defective compared to cells derived from control mice expressing the nonpathogenic hSOD1(WT) isoform. The correct in vitro myogenesis of hSOD1(G93A) primary skeletal muscle cells was rescued by the addition of a conditioned medium from healthy hSOD1(WT) myocytes, suggesting the existence of an in trans activity of secreted factors. To define a dataset of molecules participating in such safeguard action, we conducted comparative metabolomic profiling of a culture medium collected from hSOD1(G93A) and hSOD1(WT) primary myocytes and report here an altered secretion of amino acids and lipid-based signaling molecules. These findings support the urgency of better understanding the role of the skeletal muscle secretome in the regulation of the myogenic program and mechanisms of ALS pathogenesis and progression.}, } @article {pmid38066647, year = {2024}, author = {Barrios, V and Martín-Rivada, Á and Guerra-Cantera, S and Campillo-Calatayud, A and Camarneiro, RA and Graell, M and Chowen, JA and Argente, J}, title = {Reduction in Pappalysin-2 Levels and Lower IGF-I Bioavailability in Female Adolescents With Anorexia Nervosa.}, journal = {The Journal of clinical endocrinology and metabolism}, volume = {109}, number = {3}, pages = {e920-e931}, doi = {10.1210/clinem/dgad713}, pmid = {38066647}, issn = {1945-7197}, support = {FIS-PI19/00166//Ministerio de Ciencia e Innovación/ ; //European Union/ ; //Centro de Investigación Biomédica en Red Fisiopatología de Obesidad y Nutrición/ ; CD19/00008//Instituto de Salud Carlos III/ ; //Comunidad Autónoma de Madrid/ ; }, mesh = {Humans ; Female ; Adolescent ; Insulin-Like Growth Factor I/metabolism ; Insulin-Like Growth Factor Binding Protein 4 ; Insulin-Like Growth Factor Binding Protein 3 ; Insulin-Like Growth Factor Binding Protein 2 ; *Anorexia Nervosa ; Biological Availability ; Amenorrhea ; Insulin-Like Growth Factor Binding Proteins ; *Peptide Hormones ; Pregnancy-Associated Plasma Protein-A/metabolism ; }, abstract = {CONTEXT: Anorexia nervosa (AN) can cause severe undernutrition associated with alterations in the IGF axis. Pappalysins (PAPP-A, PAPP-A2) and stanniocalcins (STC-1, STC-2) modulate IGF binding-protein (IGFBP) cleavage and IGF bioavailability, but their implications in AN are unknown.

OBJECTIVE: We determined serum levels of PAPP-As and STCs in relationship with classical IGF axis parameters in female adolescents with AN and their association with nutritional status and secondary amenorrhea.

METHODS: Parameters of the IGF axis were determined in fasting serum samples of 68 female adolescents with AN at diagnosis and 62 sex- and age-matched controls. Standardized body mass index (BMI) and bone mineral density (BMD) were calculated.

RESULTS: Patients with AN had lower concentrations of total and free IGF-I, total IGFBP-3, acid-labile subunit (ALS), insulin, PAPP-A2, STC-1, and STC-2 and higher levels of IGF-II and IGFBP-2. Their free/total IGF-I ratio was decreased and the intact/total IGFBP-3 and -4 ratios increased. BMI was directly related to total IGF-I and intact IGFBP-3 and inversely with IGFBP-2 and intact IGFBP-4. Weight loss was directly correlated with intact IGFBP-4 and negatively with intact IGFBP-3, ALS, STC-2, and PAPP-A2 concentrations. BMD was directly related to intact IGFBP-3 and inversely with intact IGFBP-4 and PAPP-A2 levels. Patients with amenorrhea had lower levels of total IGF-I and IGFBP-3 than those with menses.

CONCLUSION: The reduction of PAPP-A2 in patients with AN may be involved in a decline in IGFBP cleavage, which could underlie the decrease in IGF-I bioavailability that is influenced by nutritional status and amenorrhea.}, } @article {pmid38066205, year = {2024}, author = {Reilich, P and Schöberl, F and Hiebeler, M and Tonon, M and Ludolph, AC and Senel, M}, title = {Myelitis as a side effect of tofersen therapy in SOD1-associated ALS.}, journal = {Journal of neurology}, volume = {271}, number = {4}, pages = {2114-2118}, pmid = {38066205}, issn = {1432-1459}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy/genetics ; Mutation ; *Myelitis/genetics ; Oligonucleotides/adverse effects ; Superoxide Dismutase/genetics ; Superoxide Dismutase-1/antagonists & inhibitors/genetics ; }, } @article {pmid38065418, year = {2024}, author = {Yuan, Y and Bailey, JM and Rivera-Lopez, GM and Atchison, WD}, title = {Preferential potentiation of AMPA-mediated currents in brainstem hypoglossal motoneurons by subchronic exposure of mice expressing the human superoxide dismutase 1 G93A gene mutation to neurotoxicant methylmercury in vivo.}, journal = {Neurotoxicology}, volume = {100}, number = {}, pages = {72-84}, pmid = {38065418}, issn = {1872-9711}, support = {R01 ES024064/ES/NIEHS NIH HHS/United States ; }, mesh = {Mice ; Humans ; Animals ; Superoxide Dismutase-1 ; *Amyotrophic Lateral Sclerosis/chemically induced/genetics ; *Methylmercury Compounds/toxicity ; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid/pharmacology ; Superoxide Dismutase/metabolism ; Mice, Transgenic ; Motor Neurons/metabolism ; Brain Stem/metabolism ; Mutation ; Disease Models, Animal ; Spinal Cord/metabolism ; }, abstract = {The exact causes of Amyotrophic lateral sclerosis (ALS), a progressive and fatal neurological disorder due to loss of upper and/or lower motoneurons, remain elusive. Gene-environment interactions are believed to be an important factor in the development of ALS. We previously showed that in vivo exposure of mice overexpressing the human superoxide dismutase 1 (hSOD1) gene mutation (hSOD1G93A; G93A), a mouse model for ALS, to environmental neurotoxicant methylmercury (MeHg) accelerated the onset of ALS-like phenotype. Here we examined the time-course of effects of MeHg on AMPA receptor (AMPAR)-mediated currents in hypoglossal motoneurons in brainstem slices prepared from G93A, hSOD1wild-type (hWT) and non-carrier WT mice following in vivo exposure to MeHg. Mice were exposed daily to 3 ppm (approximately 0.7 mg/kg/day) MeHg via drinking water beginning at postnatal day 28 (P28) and continued until P47, 64 or 84, then acute brainstem slices were prepared, and spontaneous excitatory postsynaptic currents (sEPSCs) or AMPA-evoked currents were examined using whole cell patch-clamp recording technique. Brainstem slices of untreated littermates were prepared at the same time points to serve as control. MeHg exposure had no significant effect on either sEPSCs or AMPA-evoked currents in slices from hWT or WT mice during any of those exposure time periods under our experimental conditions. MeHg also did not cause any significant effect on sEPSCs or AMPA-currents in G93A hypoglossal motoneurons at P47 and P64. However, at P84, MeHg significantly increased amplitudes of both sEPSCs and AMPA-evoked currents in hypoglossal motineurons from G93A mice (p < 0.05), but not the sEPSC frequency, suggesting a postsynaptic action on AMPARs. MeHg exposure did not cause any significant effect on GABAergic spontaneous inhibitory postsynaptic currents (sIPSCs). Therefore, MeHg exposure in vivo caused differential effects on AMPARs in hypoglossal motoneurons from mice with different genetic backgrounds. MeHg appears to preferentially stimulate the AMPAR-mediated currents in G93A hypoglossal motoneurons in an exposure time-dependent manner, which may contribute to the AMPAR-mediated motoneuron excitotoxicity, thereby facilitating development of ALS-like phenotype.}, } @article {pmid38064644, year = {2024}, author = {Rong, P and Rasmussen, L}, title = {A Fine-Grained Temporal Analysis of Multimodal Oral Diadochokinetic Performance to Assess Speech Impairment in Amyotrophic Lateral Sclerosis.}, journal = {American journal of speech-language pathology}, volume = {33}, number = {1}, pages = {307-332}, doi = {10.1044/2023_AJSLP-23-00177}, pmid = {38064644}, issn = {1558-9110}, mesh = {Humans ; *Speech/physiology ; *Amyotrophic Lateral Sclerosis/complications/diagnosis ; Jaw ; Speech Disorders/complications ; Speech Production Measurement ; }, abstract = {PURPOSE: This study used a semiautomated fine-grained temporal analysis to extract features of temporal oral diadochokinetic (DDK) performance across multiple modalities and tasks, from neurologically healthy and impaired individuals secondary to amyotrophic lateral sclerosis (ALS). The aims were to (a) delineate temporal oral DDK deficits relating to the neuromotor pathology of ALS and (b) identify the optimal task-feature combinations to detect speech impairment in ALS.

METHOD: Mandibular myoelectric, kinematic, and acoustic data were acquired from 13 individuals with ALS and 10 healthy controls producing three alternating motion rate tasks and one sequential motion rate task. Twenty-seven features were extracted from the multimodal data, characterizing three temporal constructs: duration/rate, variability, and coordination. The disease impacts on these features were assessed across tasks, and the task eliciting the greatest disease-related change was identified for each feature. Such "optimal" task-feature combinations were fed into logistic regression to differentiate individuals with ALS from healthy controls.

RESULTS: Temporal deficits in ALS were characterized by (a) increased duration and variability and reduced coordination of jaw muscle activities, (b) increased duration and variability and altered temporal symmetry of jaw velocity profile, (c) increased muscle-burst-to-peak-velocity duration, and (d) increased motion-to-voice onset duration. These temporal features were differentially affected across tasks. The optimal task-feature combinations, which were further clustered into three composite factors reflecting temporal variability, coarser-grained duration, and finer-grained duration, differentiated ALS from controls with an F1 score of 0.86 (precision = 1.00, recall = 0.75).

CONCLUSIONS: Temporal oral DDK deficits are likely attributed to a hierarchy of interrelated neurophysiological and biomechanical factors associated with the neuromotor pathology of ALS. These deficits, as assessed crossmodally, provide previously unavailable insights into the multifaceted timing impairment of oromotor performance in ALS. The optimal task-feature combinations targeting these deficits show promise as quantitative markers for (early) detection of speech impairment in ALS.}, } @article {pmid38064514, year = {2023}, author = {Tang, D and Zheng, K and Zhu, J and Jin, X and Bao, H and Jiang, L and Li, H and Wang, Y and Lu, Y and Liu, J and Liu, H and Tang, C and Feng, S and Dong, X and Xu, L and Yin, Y and Dang, S and Wei, X and Ren, H and Dong, B and Dai, L and Cheng, W and Wan, M and Li, Z and Chen, J and Li, H and Kong, E and Wang, K and Lu, K and Qi, S}, title = {ALS-linked C9orf72-SMCR8 complex is a negative regulator of primary ciliogenesis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {120}, number = {50}, pages = {e2220496120}, pmid = {38064514}, issn = {1091-6490}, support = {32071214//MOST | National Natural Science Foundation of China (NSFC)/ ; 32022020//MOST | National Natural Science Foundation of China (NSFC)/ ; 31970693//MOST | National Natural Science Foundation of China (NSFC)/ ; ZYYC20016//the 135 Project for Disciplines of Excellence, West China Hospital, Sichuan University/ ; ZYYC20015//the 135 Project for Disciplines of Excellence, West China Hospital, Sichuan University/ ; ZYJC18015//the 135 Project for Disciplines of Excellence, West China Hospital, Sichuan University/ ; 2022SCU12041//the Fundamental Research Funds for the Central Universities/ ; 2022NSFSC0049//the Natural Science Foundation of Sichuan, China/ ; 32201025//MOST | National Natural Science Foundation of China (NSFC)/ ; ZYGD18011//the 135 Project for Disciplines of Excellence, West China Hospital, Sichuan University/ ; }, mesh = {Animals ; Mice ; *Amyotrophic Lateral Sclerosis/metabolism ; *C9orf72 Protein/genetics/metabolism ; *Cilia/metabolism ; DNA Repeat Expansion ; *Frontotemporal Dementia/metabolism ; GTPase-Activating Proteins/metabolism ; Humans ; HEK293 Cells ; }, abstract = {Massive GGGGCC (G4C2) repeat expansion in C9orf72 and the resulting loss of C9orf72 function are the key features of ~50% of inherited amyotrophic lateral sclerosis and frontotemporal dementia cases. However, the biological function of C9orf72 remains unclear. We previously found that C9orf72 can form a stable GTPase activating protein (GAP) complex with SMCR8 (Smith-Magenis chromosome region 8). Herein, we report that the C9orf72-SMCR8 complex is a major negative regulator of primary ciliogenesis, abnormalities in which lead to ciliopathies. Mechanistically, the C9orf72-SMCR8 complex suppresses the primary cilium as a RAB8A GAP. Moreover, based on biochemical analysis, we found that C9orf72 is the RAB8A binding subunit and that SMCR8 is the GAP subunit in the complex. We further found that the C9orf72-SMCR8 complex suppressed the primary cilium in multiple tissues from mice, including but not limited to the brain, kidney, and spleen. Importantly, cells with C9orf72 or SMCR8 knocked out were more sensitive to hedgehog signaling. These results reveal the unexpected impact of C9orf72 on primary ciliogenesis and elucidate the pathogenesis of diseases caused by the loss of C9orf72 function.}, } @article {pmid38064278, year = {2024}, author = {Mao, Y and Li, Y and McGarry, B and Wang, J and Temkin-Greener, H}, title = {Home time and state regulations among Medicare beneficiaries in assisted living communities.}, journal = {Journal of the American Geriatrics Society}, volume = {72}, number = {3}, pages = {742-752}, pmid = {38064278}, issn = {1532-5415}, support = {R01 HS026893/HS/AHRQ HHS/United States ; }, mesh = {Aged ; Humans ; United States ; *Medicare ; *Quality of Life ; Nursing Homes ; Medicaid ; Chronic Disease ; }, abstract = {BACKGROUND: Home time is an important patient-centric quality metric, which has been largely unexamined among assisted living (AL) residents. Our objectives were to assess variation in home time among AL residents in the year following admission and to examine the associations with state regulations for direct care workers (DCW) training and staffing and for licensed nurse staffing.

METHODS: Medicare beneficiaries who entered AL communities in 2018 were identified, and their home time in the year following admission was measured. Home time was calculated as the percentage of time spent at home per day being alive. Resident characteristics and state regulations in DCW staffing, DCW training, and licensed staffing were measured. We used a multivariate linear regression model with AL-level fixed effects to estimate the relationship between person-level characteristics and home time. Linear regression models adjusting for resident characteristics were used to estimate the association between state regulations and residents' home time.

RESULTS: The study sample included 59,831 new Medicare beneficiary residents in 12,143 ALs. In the year following AL admission, residents spent 94% (standard deviation = 14.6) of their time at home. Several resident characteristics were associated with lower home time: Medicare-Medicaid dual eligibility, having more chronic conditions, and specific chronic conditions, for example, dementia. In states with greater regulatory specificity for DCW training and staffing, and lower specificity for licensed staffing, residents had longer adjusted home time.

CONCLUSION/IMPLICATIONS: Home time varied substantially among AL residents depending on resident characteristics and state-level regulatory specificity. AL residents eligible for Medicare and Medicaid had substantially shorter home time than the Medicare-only residents, largely due to longer time spent in nursing homes. State AL regulatory specificity for DCWs and licensed staff also impacted AL residents' home time. These findings may guide AL operators and state legislators in efforts to improve this important quality of life metric.}, } @article {pmid38063868, year = {2024}, author = {Luib, E and Demleitner, AF and Cordts, I and Westenberg, E and Rau, P and Pürner, D and Haller, B and Lingor, P}, title = {Reduced tear fluid production in neurological diseases: a cohort study in 708 patients.}, journal = {Journal of neurology}, volume = {271}, number = {4}, pages = {1824-1836}, pmid = {38063868}, issn = {1432-1459}, mesh = {Humans ; Cohort Studies ; *Nervous System Diseases ; *Motor Neuron Disease ; *Amyotrophic Lateral Sclerosis/pathology ; Brain/pathology ; *Parkinson Disease ; }, abstract = {BACKGROUND: Tear fluid (TF) production is an important component of normal ocular function. It is regulated by parasympathetic and sympathetic innervation. Because parasympathetic nerve fibers originate in the brainstem, pathology in this brain region may affect TF production. For example, a reduction in TF production has been described in patients with Parkinson's disease (PD).

METHODS: TF was collected at one center from 772 individuals, 708 of which were patients with different neurological diseases, and 64 healthy controls. Wetting lengths (WL) were recorded using Schirmer test strips with a collection time of 10 min.

RESULTS: WL correlated negatively with age and was significantly reduced in subgroups of patients with neurodegenerative diseases (NDDs) (PD, Amyotrophic lateral sclerosis (ALS), other motor neuron diseases (MNDs)), as well as inflammatory/autoimmune/infectious central nervous system (CNS) diseases and vascular CNS diseases (VCDs), even if corrected for age or sex. While temperature had a significant negative effect on TF production, other environmental factors, such as hours of sunlight and humidity, did not.

CONCLUSION: WL was altered in many neurological diseases compared to healthy controls. Most importantly, we observed a reduction of WL in NDDs, independent of age or sex. This study highlights the potential of WL as an easily obtainable parameter and suggests functional alterations in the autonomic innervation in various neurological disorders.}, } @article {pmid38063178, year = {2023}, author = {Xu, C and Zarrabeitia, M and Li, Y and Biskupek, J and Kaiser, U and Liu, X and Passerini, S}, title = {Three-Dimensional Nitrogen-Doped Carbonaceous Networks Anchored with Cobalt as Separator Modification Layers for Low-Polarization and Long-Lifespan Aluminum-Sulfur Batteries.}, journal = {ACS nano}, volume = {17}, number = {24}, pages = {25234-25242}, doi = {10.1021/acsnano.3c08476}, pmid = {38063178}, issn = {1936-086X}, abstract = {Aluminum-sulfur (Al-S) batteries have attracted extensive interest due to their high theoretical energy density, inherent safety, and low cost. However, severe polarization and poor cycling performance significantly limit the development of Al-S batteries. Herein, three-dimensional (3D) nitrogen-doped carbonaceous networks anchored with cobalt (Co@CMel-ZIF) is proposed as a separator modification layer to mitigate these issues, prepared via carbonizations of a mixture of ZIF-7, melamine, and CoCl2. It exhibits a 3D network structure with a moderate surface area and high average pore diameter, which is demonstrated to be effective in adsorbing the aluminum polysulfides and hindering the mobility of polysulfides across the separator for enhanced cyclic stability of Al-S batteries. Meanwhile, Co@CMel-ZIF are characterized by abundant catalytic pyridinic-N and Co-Nx active sites that effectively eliminate the barrier of sulfides' conversion and thereby facilitate the polarization reduction. As a result, Al-S cells based on the separator modified with Co@CMel-ZIF exhibit a low voltage polarization of 0.47 V under the current density of 50 mA g[-1] at 20 °C and a high discharge specific capacity of 503 mAh g[-1] after 150 cycles. In contrast, the cell employing a bare separator exhibits a polarization of 1.01 V and a discharge capacity of 300 mAh g[-1] after 70 cycles under the same conditions. This work demonstrates that modifying the separators is a promising strategy to mitigate the high polarization and poor cyclability of Al-S batteries.}, } @article {pmid38062520, year = {2023}, author = {Rahman, MAA and Elghobashy, MR and Zaazaa, HE and El-Mosallamy, SS}, title = {Novel analytical method based on chemometric models applied to UV-Vis spectrophotometric data for simultaneous determination of Etoricoxib and Paracetamol in presence of Paracetamol impurities.}, journal = {BMC chemistry}, volume = {17}, number = {1}, pages = {176}, pmid = {38062520}, issn = {2661-801X}, abstract = {The multivariate models that are used for spectral data analysis have many beneficial applications, and one of the important applications is the analysis of drugs and their impurities. Three Chemometrically-assisted spectrophotometric models have been proposed and validated. The proposed models are Partial Least Squares (PLS), Artificial Neural Networks (ANN), and Multivariate Curve Resolution-Alternating Least Squares (MCR-ALS). The advanced chemometric models were applied to resolve the significantly overlapping spectra of Etoricoxib (ETO) and Paracetamol (PCM), along with impurities of PCM namely; P-aminophenol (PAP) and P-hydroxy acetophenone (PHA). The proposed models succeeded in simultaneously analyzing the mixture of ETO and PCM along with the impurities of PCM. So, the proposed techniques can be used without requiring a separation step in the analysis of pharmaceutical formulation. Moreover, no significant differences were found when the results of the suggested and published chemometric models were compared statistically with the reported HPLC method.}, } @article {pmid38062485, year = {2023}, author = {Shen, T and Vogel, JW and Duda, J and Phillips, JS and Cook, PA and Gee, J and Elman, L and Quinn, C and Amado, DA and Baer, M and Massimo, L and Grossman, M and Irwin, DJ and McMillan, CT}, title = {Novel data-driven subtypes and stages of brain atrophy in the ALS-FTD spectrum.}, journal = {Translational neurodegeneration}, volume = {12}, number = {1}, pages = {57}, pmid = {38062485}, issn = {2047-9158}, support = {K08 NS114106/NS/NINDS NIH HHS/United States ; P01 AG066597/AG/NIA NIH HHS/United States ; P30 AG072979/AG/NIA NIH HHS/United States ; R01 NS109260/NS/NINDS NIH HHS/United States ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnostic imaging/genetics ; *Frontotemporal Dementia/diagnostic imaging/genetics ; *Neurodegenerative Diseases/pathology ; Brain/metabolism ; DNA-Binding Proteins/genetics/metabolism ; Atrophy/genetics/complications/pathology ; }, abstract = {BACKGROUND: TDP-43 proteinopathies represent a spectrum of neurological disorders, anchored clinically on either end by amyotrophic lateral sclerosis (ALS) and frontotemporal degeneration (FTD). The ALS-FTD spectrum exhibits a diverse range of clinical presentations with overlapping phenotypes, highlighting its heterogeneity. This study was aimed to use disease progression modeling to identify novel data-driven spatial and temporal subtypes of brain atrophy and its progression in the ALS-FTD spectrum.

METHODS: We used a data-driven procedure to identify 13 anatomic clusters of brain volume for 57 behavioral variant FTD (bvFTD; with either autopsy-confirmed TDP-43 or TDP-43 proteinopathy-associated genetic variants), 103 ALS, and 47 ALS-FTD patients with likely TDP-43. A Subtype and Stage Inference (SuStaIn) model was trained to identify subtypes of individuals along the ALS-FTD spectrum with distinct brain atrophy patterns, and we related subtypes and stages to clinical, genetic, and neuropathological features of disease.

RESULTS: SuStaIn identified three novel subtypes: two disease subtypes with predominant brain atrophy in either prefrontal/somatomotor regions or limbic-related regions, and a normal-appearing group without obvious brain atrophy. The limbic-predominant subtype tended to present with more impaired cognition, higher frequencies of pathogenic variants in TBK1 and TARDBP genes, and a higher proportion of TDP-43 types B, E and C. In contrast, the prefrontal/somatomotor-predominant subtype had higher frequencies of pathogenic variants in C9orf72 and GRN genes and higher proportion of TDP-43 type A. The normal-appearing brain group showed higher frequency of ALS relative to ALS-FTD and bvFTD patients, higher cognitive capacity, higher proportion of lower motor neuron onset, milder motor symptoms, and lower frequencies of genetic pathogenic variants. The overall SuStaIn stages also correlated with evidence for clinical progression including longer disease duration, higher King's stage, and cognitive decline. Additionally, SuStaIn stages differed across clinical phenotypes, genotypes and types of TDP-43 pathology.

CONCLUSIONS: Our findings suggest distinct neurodegenerative subtypes of disease along the ALS-FTD spectrum that can be identified in vivo, each with distinct brain atrophy, clinical, genetic and pathological patterns.}, } @article {pmid38062079, year = {2023}, author = {Bowden, M and Beswick, E and Tam, J and Perry, D and Smith, A and Newton, J and Chandran, S and Watts, O and Pal, S}, title = {A systematic review and narrative analysis of digital speech biomarkers in Motor Neuron Disease.}, journal = {NPJ digital medicine}, volume = {6}, number = {1}, pages = {228}, pmid = {38062079}, issn = {2398-6352}, abstract = {Motor Neuron Disease (MND) is a progressive and largely fatal neurodegeneritve disorder with a lifetime risk of approximately 1 in 300. At diagnosis, up to 25% of people with MND (pwMND) exhibit bulbar dysfunction. Currently, pwMND are assessed using clinical examination and diagnostic tools including the ALS Functional Rating Scale Revised (ALS-FRS(R)), a clinician-administered questionnaire with a single item on speech intelligibility. Here we report on the use of digital technologies to assess speech features as a marker of disease diagnosis and progression in pwMND. Google Scholar, PubMed, Medline and EMBASE were systematically searched. 40 studies were evaluated including 3670 participants; 1878 with a diagnosis of MND. 24 studies used microphones, 5 used smartphones, 6 used apps, 2 used tape recorders and 1 used the Multi-Dimensional Voice Programme (MDVP) to record speech samples. Data extraction and analysis methods varied but included traditional statistical analysis, CSpeech, MATLAB and machine learning (ML) algorithms. Speech features assessed also varied and included jitter, shimmer, fundamental frequency, intelligible speaking rate, pause duration and syllable repetition. Findings from this systematic review indicate that digital speech biomarkers can distinguish pwMND from healthy controls and can help identify bulbar involvement in pwMND. Preliminary evidence suggests digitally assessed acoustic features can identify more nuanced changes in those affected by voice dysfunction. No one digital speech biomarker alone is consistently able to diagnose or prognosticate MND. Further longitudinal studies involving larger samples are required to validate the use of these technologies as diagnostic tools or prognostic biomarkers.}, } @article {pmid38061694, year = {2024}, author = {Ai, Y and Li, F and Hou, Y and Li, X and Li, W and Qin, K and Suo, X and Lei, D and Shang, H and Gong, Q}, title = {Differential cortical gray matter changes in early- and late-onset patients with amyotrophic lateral sclerosis.}, journal = {Cerebral cortex (New York, N.Y. : 1991)}, volume = {34}, number = {1}, pages = {}, doi = {10.1093/cercor/bhad426}, pmid = {38061694}, issn = {1460-2199}, support = {2022YFC2009900//National Key Research and Development Program of China/ ; 81621003//National Natural Science Foundation of China/ ; }, mesh = {Humans ; Gray Matter/diagnostic imaging/pathology ; *Amyotrophic Lateral Sclerosis/diagnostic imaging/pathology ; Magnetic Resonance Imaging ; Brain/pathology ; *Motor Cortex/pathology ; }, abstract = {Age at onset may be an important feature associated with distinct subtypes of amyotrophic lateral sclerosis (ALS). Little is known about the neuropathological mechanism of early-onset ALS (EO-ALS) and late-onset ALS (LO-ALS). Ninety ALS patients were divided into EO-ALS and LO-ALS group, and 128 healthy controls were matched into young controls(YCs) and old controls (OCs). A voxel-based morphometry approach was employed to investigate differences in gray matter volume (GMV). Significant age at onset-by-diagnosis interactions were found in the left parietal operculum, left precentral gyrus, bilateral postcentral gyrus, right occipital gyrus, and right orbitofrontal cortex. Post hoc analysis revealed a significant decrease in GMV in all affected regions of EO-ALS patients compared with YCs, with increased GMV in 5 of the 6 brain regions, except for the right orbitofrontal cortex, in LO-ALS patients compared with OCs. LO-ALS patients had a significantly increased GMV than EO-ALS patients after removing the aging effect. Correspondingly, GMV of the left postcentral gyrus correlated with disease severity in the 2 ALS groups. Our findings suggested that the pathological mechanisms in ALS patients with different ages at onset might differ. These findings provide unique insight into the clinical and biological heterogeneity of the 2 ALS subtypes.}, } @article {pmid38061331, year = {2023}, author = {Yadav, A and Matson, KJE and Lee, D and Alkaslasi, MR and Roome, RB and Ward, ME and Phatnani, H and Le Pichon, CE and Menon, V and Levine, AJ}, title = {A reproducible signature of cytoskeletal and ALS-related genes in human motoneurons.}, journal = {Neuron}, volume = {111}, number = {23}, pages = {3742-3744}, doi = {10.1016/j.neuron.2023.10.034}, pmid = {38061331}, issn = {1097-4199}, support = {R01 NS116350/NS/NINDS NIH HHS/United States ; }, } @article {pmid38059522, year = {2024}, author = {Xu, R and Wang, X and Zhu, S and Jiang, B and Wan, J and Ma, J and Yu, Y and Yu, L and Fang, Q and Hu, C and Zhu, M}, title = {Assessment of Cerebral White Matter Involvement in Amyotrophic Lateral Sclerosis Patients With Disease Progression and Cognitive Impairment by Fixel-Based Analysis and Neurite Orientation Dispersion and Density Imaging.}, journal = {Journal of magnetic resonance imaging : JMRI}, volume = {60}, number = {3}, pages = {900-908}, doi = {10.1002/jmri.29171}, pmid = {38059522}, issn = {1522-2586}, support = {LK2021017//Application Fundamental Research Program of the Jiangsu Provincial Health Commission's Elderly Health Project/ ; UTPIE2023006//the Undergraduate Training Program for Innovation and Entrepreneurship, Soochow University/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnostic imaging/pathology ; Female ; Male ; Middle Aged ; *Disease Progression ; *White Matter/diagnostic imaging/pathology ; *Neurites/pathology ; *Cognitive Dysfunction/diagnostic imaging ; Aged ; Prospective Studies ; Image Processing, Computer-Assisted/methods ; Brain/diagnostic imaging/pathology ; Magnetic Resonance Imaging/methods ; Diffusion Tensor Imaging/methods ; Diffusion Magnetic Resonance Imaging ; }, abstract = {BACKGROUND: Previous studies using emerging diffusion MRI techniques have revealed damage to the white matter (WM) microstructure in amyotrophic lateral sclerosis (ALS), particularly the influence of crossed fibers, but there is a lack of subgroup analyses.

PURPOSE: To detect WM microstructural changes in ALS patients using fixel-based analysis (FBA) and neurite orientation dispersion and density imaging (NODDI) MRI.

STUDY TYPE: Prospective.

POPULATION: Thirty-six ALS patients (aged 60.50 ± 9.5 years) and 25 healthy controls (HCs) (aged 58.90 ± 8.1 years).

FIELD STRENGTH/SEQUENCE: 3 T; NODDI and FBA (b-values = 0, 1000, and 2500 seconds/mm[2]).

ASSESSMENT: Subgroups were performed according to progression rate and cognition, including fast and slow progression (FP/SP), ALS with and without cognitive impairment (ALS-ci/ALS-nci). Fiber density (FD), fiber-bundle cross-section (FC), combined fiber density and cross-section (FDC), neurite density index (NDI), orientation dispersion index (ODI), isotropic volume fraction (ISO), and fractional anisotropy (FA) were calculated and their correlation with clinical variables examined.

STATISTICAL TESTING: Chi-square test, Mann-Whitney U test, two-sample t test, partial correlation analysis, and false discovery rate (FDR) corrected. A P-value <0.05 was considered significant.

RESULTS: ALS patients had lower FD and FDC values predominantly in the corticospinal tract (CST) and corpus callosum (CC) regions, as well as lower NDI value in the CC, radial crown, and internal capsule compared to HCs. Subgroup analysis based on progression rate and cognitive function showed significant differences in FBA results. The FC in the right CST region was significantly lower in the FP than SP, and the FD in the CC region was significantly lower in the ALS-ci than ALS-nci. Furthermore, a negative correlation was found between the mean FC value and the rate of progression in ALS patients (r = -0.408).

DATA CONCLUSION: FBA is a powerful tool for detecting complex cerebral WM microstructural damage for evaluating ALS cognition and disease progression.}, } @article {pmid38057503, year = {2023}, author = {Vernikouskaya, I and Müller, HP and Roselli, F and Ludolph, AC and Kassubek, J and Rasche, V}, title = {AI-assisted quantification of hypothalamic atrophy in amyotrophic lateral sclerosis by convolutional neural network-based automatic segmentation.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {21505}, pmid = {38057503}, issn = {2045-2322}, support = {LU 336/15-1//Deutsche Forschungsgemeinschaft/ ; 01GM1103A//German Network for Motor Neuron Diseases/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnostic imaging ; Neural Networks, Computer ; Magnetic Resonance Imaging/methods ; Neuroimaging/methods ; Atrophy ; Image Processing, Computer-Assisted/methods ; }, abstract = {The hypothalamus is a small structure of the brain with an essential role in metabolic homeostasis, sleep regulation, and body temperature control. Some neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and dementia syndromes are reported to be related to hypothalamic volume alterations. Despite its crucial role in human body regulation, neuroimaging studies of this structure are rather scarce due to work-intensive operator-dependent manual delineations from MRI and lack of automated segmentation tools. In this study we present a fully automatic approach based on deep convolutional neural networks (CNN) for hypothalamic segmentation and volume quantification. We applied CNN of U-Net architecture with EfficientNetB0 backbone to allow for accurate automatic hypothalamic segmentation in seconds on a GPU. We further applied our approach for the quantification of the normalized hypothalamic volumes to a large neuroimaging dataset of 432 ALS patients and 112 healthy controls (without the ground truth labels). Using the automated volumetric analysis, we could reproduce hypothalamic atrophy findings associated with ALS by detecting significant volume differences between ALS patients and controls at the group level. In conclusion, a fast and unbiased AI-assisted hypothalamic quantification method is introduced in this study (whose acceptance rate based on the outlier removal strategy was estimated to be above 95%) and made publicly available for researchers interested in the conduction of hypothalamus studies at a large scale.}, } @article {pmid38056528, year = {2024}, author = {Camiña-Conforto, G and Vilarrasa, E and Cabo, F and Fernández-Vela, J and Pousa, M and Romaní, J}, title = {Response letter to "Tracing the origins of setons in hidradenitis suppurativa: A commentary to Vilarrasa et al's 'Drainage setons for the management of sinus tracts in hidradenitis suppurativa'".}, journal = {Journal of the American Academy of Dermatology}, volume = {90}, number = {4}, pages = {e141-e142}, doi = {10.1016/j.jaad.2023.11.049}, pmid = {38056528}, issn = {1097-6787}, mesh = {Humans ; *Hidradenitis Suppurativa ; Inflammation ; }, } @article {pmid38056310, year = {2024}, author = {Guo, Y and Guan, T and Yu, Q and Sanghai, N and Shafiq, K and Li, M and Jiao, X and Na, D and Zhang, G and Kong, J}, title = {ALS-linked SOD1 mutations impair mitochondrial-derived vesicle formation and accelerate aging.}, journal = {Redox biology}, volume = {69}, number = {}, pages = {102972}, pmid = {38056310}, issn = {2213-2317}, mesh = {Animals ; Humans ; Infant ; Mice ; Middle Aged ; Aging/genetics ; *Amyotrophic Lateral Sclerosis/genetics/metabolism ; Disease Models, Animal ; Mice, Transgenic ; Motor Neurons ; Mutation ; *Sirtuins/metabolism ; Superoxide Dismutase/metabolism ; Superoxide Dismutase-1/genetics/metabolism ; }, abstract = {Oxidative stress (OS) is regarded as the dominant theory for aging. While compelling correlative data have been generated to support the OS theory, a direct cause-and-effect relationship between the accumulation of oxidation-mediated damage and aging has not been firmly established. Superoxide dismutase 1 (SOD1) is a primary antioxidant in all cells. It is, however, susceptible to oxidation due to OS and gains toxic properties to cells. This study investigates the role of oxidized SOD1 derived from amyotrophic lateral sclerosis (ALS) linked SOD1 mutations in cell senescence and aging. Herein, we have shown that the cell line NSC34 expressing the G93A mutation of human SOD1 (hSOD1[G93A]) entered premature senescence as evidenced by a decreased number of the 5-ethynyl-2'-deoxyuridine (EdU)-positive cells. There was an upregulation of cellular senescence markers compared to cells expressing the wild-type human SOD1 (hSOD1[WT]). Transgenic mice carrying the hSOD1[G93A] gene showed aging phenotypes at an early age (135 days) with high levels of P53 and P16 but low levels of SIRT1 and SIRT6 compared with age-matched hSOD1[WT] transgenic mice. Notably, the levels of oxidized SOD1 were significantly elevated in both the senescent NSC34 cells and 135-day hSOD1[G93A] mice. Selective removal of oxidized SOD1 by our CT4-directed autophagy significantly decelerated aging, indicating that oxidized SOD1 is a causal factor of aging. Intriguingly, mitochondria malfunctioned in both senescent NSC34 cells and middle-aged hSOD[G93A] transgenic mice. They exhibited increased production of mitochondrial-derived vesicles (MDVs) in response to mild OS in mutant humanSOD1 (hSOD1) transgenic mice at a younger age; however, the mitochondrial response gradually declined with aging. In conclusion, our data show that oxidized SOD1 derived from ALS-linked SOD1 mutants is a causal factor for cellular senescence and aging. Compromised mitochondrial responsiveness to OS may serve as an indicator of premature aging.}, } @article {pmid38056247, year = {2024}, author = {Jiang, H and Zhang, Y and Hu, J and Wang, Z and Li, G and Lu, Y}, title = {An alternative spliced UPF2 transcript in pancreatic inflammatory myofibroblastic tumors.}, journal = {Biochemical and biophysical research communications}, volume = {691}, number = {}, pages = {149306}, doi = {10.1016/j.bbrc.2023.149306}, pmid = {38056247}, issn = {1090-2104}, mesh = {Humans ; *Neoplasms ; Nonsense Mediated mRNA Decay ; RNA, Messenger/genetics/metabolism ; RNA-Binding Proteins/metabolism ; }, abstract = {BACKGROUND: Inflammatory myofibroblastic tumors (IMTs) are characterized by myofibroblast proliferation and an inflammatory cell infiltrate. Our previous study on IMTs reveals that disrupt NMD pathway causes to lower the threshold for triggering the immune cell infiltration, thereby resulting in inappropriate immune activation. However, myofibroblast differentiation and proliferation is not yet known.

METHODS: RT-PCR, RT-qPCR, DNA sequence, western bolt, 5'race analysis and site-specific mutagenesis were used in this study.

RESULTS: Here, an alternative spliced (ALS) UPF2 mRNA skipping exon 2 and 3 and corresponding to the truncated UPF2 protein were found in 2 pancreatic IMTs. We showed that the uORF present in the 5'UTR of UPF2 mRNA is responsible for the translation inhibition, whiles ALS UPF2 is more facilitated to be translated into the truncated UPF2 protein. Several mRNA targets of the NMD were upregulated in IMT samples, indicating that the truncated UPF2 function is strongly perturbed, resulted in disrupted NMD pathway in IMTs. These upregulated NMD targets included cdkn1a expression and the generation of high levels of p21 (waf1/cip1), which may contribute to triggering IMTs.

CONCLUSION: The disrupt UPFs/NMD pathway may link to molecular alteration associated with differentiation and proliferation for IMTs.}, } @article {pmid38056214, year = {2024}, author = {Jia, F and Zhang, B and Yu, W and Chen, Z and Xu, W and Zhao, W and Wang, Z}, title = {Exploring the cuproptosis-related molecular clusters in the peripheral blood of patients with amyotrophic lateral sclerosis.}, journal = {Computers in biology and medicine}, volume = {168}, number = {}, pages = {107776}, doi = {10.1016/j.compbiomed.2023.107776}, pmid = {38056214}, issn = {1879-0534}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics ; *Neurodegenerative Diseases ; Algorithms ; Calibration ; Cluster Analysis ; Apoptosis ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive and lethal neurodegenerative disease. Several studies have suggested the involvement of cuproptosis in its pathogenesis. In this research, we intend to explore the cuproptosis-related molecular clusters in ALS and develop a novel cuproptosis-related genes prediction model.

METHODS: The peripheral blood gene expression data was downloaded from the Gene Expression Omnibus (GEO) online database. Based on the GSE112681 dataset, we investigated the critical cuproptosis-related genes (CuRGs) and pathological clustering of ALS. The immune microenvironment features of the peripheral blood in ALS patients were also examined using the CIBERSORT algorithm. Cluster-specific hub genes were determined by the WGCNA. The most accurate prediction model was selected by comparing the performance of four machine learning techniques. ROC curves and two independent datasets were applied to validate the prediction accuracy. The available compounds targeting these hub genes were filtered to investigate their efficacy in treating ALS.

RESULTS: We successfully determined four critical cuproptosis-related genes and two pathological clusters with various immune profiles and biological characteristics in ALS. Functional analysis showed that genes in Cluster1 were primarily enriched in pathways closely associated with immunity. The Support Vector Machine (SVM) model exhibited the best discrimination properties with a large area under the curve (AUC = 0.862). Five hub prediction genes (BAP1, SMG1, BCLAF1, DHX15, EIF4G2) were selected to establish a nomogram model, suggesting significant risk prediction potential for ALS. The accuracy of this model in predicting ALS incidence was also demonstrated through calibration curves, nomograms, and decision curve analysis. Finally, three drugs targeting BAP1 were determined through drug-gene interactions.

CONCLUSION: This study elucidated the complex associations between cuproptosis and ALS and constructed a satisfactory predictive model to explore the pathological characteristics of different clusters in ALS patients.}, } @article {pmid38053196, year = {2023}, author = {Lombardo, FL and Spila Alegiani, S and Mayer, F and Cipriani, M and Lo Giudice, M and Ludolph, AC and McDermott, CJ and Corcia, P and Van Damme, P and Van den Berg, LH and Hardiman, O and Nicolini, G and Vanacore, N and Dickie, B and Albanese, A and Puopolo, M and , }, title = {A randomized double-blind clinical trial on safety and efficacy of tauroursodeoxycholic acid (TUDCA) as add-on treatment in patients affected by amyotrophic lateral sclerosis (ALS): the statistical analysis plan of TUDCA-ALS trial.}, journal = {Trials}, volume = {24}, number = {1}, pages = {792}, pmid = {38053196}, issn = {1745-6215}, support = {755094//Horizon 2020 Framework Programme/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/drug therapy ; Riluzole ; *Neuroprotective Agents/adverse effects ; Reproducibility of Results ; Double-Blind Method ; Treatment Outcome ; Disease Progression ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a highly debilitating neurodegenerative condition. Despite recent advancements in understanding the molecular mechanisms underlying ALS, there have been no significant improvements in therapeutic options for ALS patients in recent years. Currently, there is no cure for ALS, and the only approved treatment in Europe is riluzole, which has been shown to slow the disease progression and prolong survival by approximately 3 months. Recently, tauroursodeoxycholic acid (TUDCA) has emerged as a promising and effective treatment for neurodegenerative diseases due to its neuroprotective activities.

METHODS: The ongoing TUDCA-ALS study is a double-blinded, parallel arms, placebo-controlled, randomized multicenter phase III trial with the aim to assess the efficacy and safety of TUDCA as add-on therapy to riluzole in patients with ALS. The primary outcome measure is the treatment response defined as a minimum of 20% improvement in the ALS Functional Rating Scale-Revised (ALSFRS-R) slope during the randomized treatment period (18 months) compared to the lead-in period (3 months). Randomization will be stratified by country. Primary analysis will be conducted based on the intention-to-treat principle through an unadjusted logistic regression model. Patient recruitment commenced on February 22, 2019, and was closed on December 23, 2021. The database will be locked in September 2023.

DISCUSSION: This paper provides a comprehensive description of the statistical analysis plan in order to ensure the reproducibility of the analysis and avoid selective reporting of outcomes and data-driven analysis. Sensitivity analyses have been included in the protocol to assess the impact of intercurrent events related to the coronavirus disease 2019. By focusing on clinically meaningful and robust outcomes, this trial aims to determine whether TUDCA can be effective in slowing the disease progression in patients with ALS.

TRIAL REGISTRATION: ClinicalTrials.gov NCT03800524 . Registered on January 11, 2019.}, } @article {pmid38052682, year = {2024}, author = {Festa, LK and Grinspan, JB and Jordan-Sciutto, KL}, title = {White matter injury across neurodegenerative disease.}, journal = {Trends in neurosciences}, volume = {47}, number = {1}, pages = {47-57}, pmid = {38052682}, issn = {1878-108X}, support = {R01 MH098742/MH/NIMH NIH HHS/United States ; R01 MH126773/MH/NIMH NIH HHS/United States ; R21 MH118121/MH/NIMH NIH HHS/United States ; T32 AI007632/AI/NIAID NIH HHS/United States ; }, mesh = {Humans ; *Neurodegenerative Diseases/metabolism ; *White Matter/metabolism ; *Alzheimer Disease ; *Parkinson Disease ; *Amyotrophic Lateral Sclerosis ; }, abstract = {Oligodendrocytes (OLs), the myelin-generating cells of the central nervous system (CNS), are active players in shaping neuronal circuitry and function. It has become increasingly apparent that injury to cells within the OL lineage plays a central role in neurodegeneration. In this review, we focus primarily on three degenerative disorders in which white matter loss is well documented: Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). We discuss clinical data implicating white matter injury as a key feature of these disorders, as well as shared and divergent phenotypes between them. We examine the cellular and molecular mechanisms underlying the alterations to OLs, including chronic neuroinflammation, aggregation of proteins, lipid dysregulation, and organellar stress. Last, we highlight prospects for therapeutic intervention targeting the OL lineage to restore function.}, } @article {pmid38052485, year = {2024}, author = {Din Abdul Jabbar, MA and Guo, L and Nag, S and Guo, Y and Simmons, Z and Pioro, EP and Ramasamy, S and Yeo, CJJ}, title = {Predicting amyotrophic lateral sclerosis (ALS) progression with machine learning.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {25}, number = {3-4}, pages = {242-255}, doi = {10.1080/21678421.2023.2285443}, pmid = {38052485}, issn = {2167-9223}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis ; Bayes Theorem ; Disease Progression ; Machine Learning ; Databases, Factual ; }, abstract = {OBJECTIVE: To predict ALS progression with varying observation and prediction window lengths, using machine learning (ML).

METHODS: We used demographic, clinical, and laboratory parameters from 5030 patients in the Pooled Resource Open-Access ALS Clinical Trials (PRO-ACT) database to model ALS disease progression as fast (at least 1.5 points decline in ALS Functional Rating Scale-Revised (ALSFRS-R) per month) or non-fast, using Extreme Gradient Boosting (XGBoost) and Bayesian Long Short Term Memory (BLSTM). XGBoost identified predictors of progression while BLSTM provided a confidence level for each prediction.

RESULTS: ML models achieved area under receiver-operating-characteristics curve (AUROC) of 0.570-0.748 and were non-inferior to clinician assessments. Performance was similar with observation lengths of a single visit, 3, 6, or 12 months and on a holdout validation dataset, but was better for longer prediction lengths. 21 important predictors were identified, with the top 3 being days since disease onset, past ALSFRS-R and forced vital capacity. Nonstandard predictors included phosphorus, chloride and albumin. BLSTM demonstrated higher performance for the samples about which it was most confident. Patient screening by models may reduce hypothetical Phase II/III clinical trial sizes by 18.3%.

CONCLUSION: Similar accuracies across ML models using different observation lengths suggest that a clinical trial observation period could be shortened to a single visit and clinical trial sizes reduced. Confidence levels provided by BLSTM gave additional information on the trustworthiness of predictions, which could aid decision-making. The identified predictors of ALS progression are potential biomarkers and therapeutic targets for further research.}, } @article {pmid38052188, year = {2024}, author = {Crowe, AL and Kerr, K and McAneney, H and McMullan, J and Duffy, G and McKnight, AJ}, title = {Stakeholder Perceptions of Complementary and Integrative Medicines from People Living with Rare Diseases in Northern Ireland: A Mixed Methods Study.}, journal = {Complementary medicine research}, volume = {31}, number = {2}, pages = {107-115}, pmid = {38052188}, issn = {2504-2106}, mesh = {Humans ; Northern Ireland ; *Complementary Therapies/statistics & numerical data/psychology ; *Rare Diseases/therapy ; *Integrative Medicine ; Female ; Surveys and Questionnaires ; Male ; Adult ; Middle Aged ; Health Personnel/psychology ; *Stakeholder Participation ; }, abstract = {INTRODUCTION: Only 5% of rare diseases have an approved treatment available, therefore patients often utilise complementary and integrative medicines (CIMs) to help manage their condition. Limited high-quality evidence-based studies are available which support the effectiveness of CIM, as it is difficult to show that an outcome is a direct result of the CIM intervention and not due to bias. Patients and healthcare professionals must weigh up the evidence quality, safety, efficacy, practical logistics, and financial implications of utilising CIM for rare diseases. This study aimed to elucidate perspectives of stakeholders (individuals with rare diseases, carers, family members, CIM practitioners and healthcare professionals), on the usage of CIM for rare diseases across Northern Ireland.

METHODS: This was a mixed methods study. An online survey was open from January to February 2019 (n = 29 responses). Themes identified from the survey were then discussed with stakeholders in a semi-structured discussion workshop in March 2019.

RESULTS: A limited number of participants responded to the survey (n = 29). Some individuals with rare diseases reported CIM as effective in the management of their condition, in particular acupuncture, dietary supplements, herbal medicines, homoeopathy, hydrotherapy, kinesiology, mindfulness, pilates, reflexology, tai chi, and yoga. However, a number of respondents (n = 7) experienced a negative side effect from CIM. Workshop participants raised concerns over the lack of information available about CIM and rare disease. Both the survey and workshop identified inequality of access with participants reporting CIM to be expensive.

CONCLUSIONS: More information, high-quality research, and education about CIM are required for patients and healthcare professionals to help make informed decisions about the usage of CIM for rare diseases. Improved communication, information, and health and social care in general would help individuals be more confident and knowledgeable about therapeutic options in relation to their rare disease(s).

UNLABELLED: EinleitungNur für fünf Prozent der seltenen Erkrankungen existiert eine zugelassene Behandlung, weshalb Patienten häufig komplementäre und integrative Medizin (CIM) nutzen, um ihre Krankheit zu behandeln. Es liegen nur wenige qualitativ hochwertige evidenzbasierte Studien vor, die die Wirksamkeit von CIM stützen, da sich schwer nachweisen lässt, dass ein Behandlungsergebnis direkt durch die CIM-Intervention bedingt und nicht Folge einer Verzerrung ist. Patienten und Angehörige der Gesundheitsberufe müssen die Qualität der Evidenz, die Sicherheit und Wirksamkeit sowie praktische logistische Aspekte und die finanziellen Folgen der Anwendung von CIM bei seltenen Erkrankungen abwägen. Mit der vorliegenden Studie sollte die Perspektive der Betroffenen (Menschen mit seltenen Erkrankungen, Betreuungspersonen, Familienangehörige, CIM-Praktiker und Angehörige der Gesundheitsberufe) in Bezug auf die Anwendung von CIM bei seltenen Erkrankungen in Nordirland untersucht werden.MethodenEs handelte sich um eine Studie mit gemischten Methoden. Eine Online-Umfrage war von Januar bis Februar 2019 geöffnet (n = 29 Antworten). Die in der Umfrage ermittelten Themen wurden anschließend im März 2019 im Rahmen eines halbstrukturierten Diskussionsworkshops mit den Betroffenen erörtert.ErgebnisseEine begrenzte Anzahl von Teilnehmern antwortete auf die Umfrage (n = 29). Einige Personen mit seltenen Erkrankungen gaben an, dass CIM bei der Behandlung ihrer Erkrankung wirksam war, insbesondere Akupunktur, Nahrungsergänzungsmittel, pflanzliche Arzneimittel, Homöopathie, Hydrotherapie, Kinesiologie, Achtsamkeit, Pilates, Reflexologie, Tai Chi und Yoga. Einige Befragte (n = 7) berichteten jedoch über negative Nebenwirkungen der CIM. Die Workshop-Teilnehmer äußerten Bedenken in Bezug auf den Mangel an Informationen über CIM und seltene Erkrankungen. Sowohl in der Umfrage als auch im Workshop zeigte sich eine Ungleichheit beim Zugang zu CIM und die Teilnehmer berichteten, dass CIM teuer sei.SchlussfolgerungenPatienten und Angehörige der Gesundheitsberufe benötigen mehr Informationen, qualitativ hochwertige Forschung und Aufklärung über CIM, um fundierte Entscheidungen über die Anwendung von CIM bei seltenen Erkrankungen treffen zu können. Eine bessere Kommunikation, Information sowie gesundheitliche und soziale Versorgung im Allgemeinen würden zu mehr Selbstvertrauen und Wissen der Betroffenen über die therapeutischen Möglichkeiten im Zusammenhang mit ihrer seltenen Erkrankung beitragen.}, } @article {pmid38051886, year = {2024}, author = {Liang, S and Zhou, J and Yu, X and Lu, S and Liu, R}, title = {Neuronal conversion from glia to replenish the lost neurons.}, journal = {Neural regeneration research}, volume = {19}, number = {7}, pages = {1446-1453}, pmid = {38051886}, issn = {1673-5374}, abstract = {Neuronal injury, aging, and cerebrovascular and neurodegenerative diseases such as cerebral infarction, Alzheimer's disease, Parkinson's disease, frontotemporal dementia, amyotrophic lateral sclerosis, and Huntington's disease are characterized by significant neuronal loss. Unfortunately, the neurons of most mammals including humans do not possess the ability to self-regenerate. Replenishment of lost neurons becomes an appealing therapeutic strategy to reverse the disease phenotype. Transplantation of pluripotent neural stem cells can supplement the missing neurons in the brain, but it carries the risk of causing gene mutation, tumorigenesis, severe inflammation, and obstructive hydrocephalus induced by brain edema. Conversion of neural or non-neural lineage cells into functional neurons is a promising strategy for the diseases involving neuron loss, which may overcome the above-mentioned disadvantages of neural stem cell therapy. Thus far, many strategies to transform astrocytes, fibroblasts, microglia, Müller glia, NG2 cells, and other glial cells to mature and functional neurons, or for the conversion between neuronal subtypes have been developed through the regulation of transcription factors, polypyrimidine tract binding protein 1 (PTBP1), and small chemical molecules or are based on a combination of several factors and the location in the central nervous system. However, some recent papers did not obtain expected results, and discrepancies exist. Therefore, in this review, we discuss the history of neuronal transdifferentiation, summarize the strategies for neuronal replenishment and conversion from glia, especially astrocytes, and point out that biosafety, new strategies, and the accurate origin of the truly converted neurons in vivo should be focused upon in future studies. It also arises the attention of replenishing the lost neurons from glia by gene therapies such as up-regulation of some transcription factors or down-regulation of PTBP1 or drug interference therapies.}, } @article {pmid38051885, year = {2024}, author = {Helgudóttir, SS and Mørkholt, AS and Lichota, J and Bruun-Nyzell, P and Andersen, MC and Kristensen, NMJ and Johansen, AK and Zinn, MR and Jensdóttir, HM and Nieland, JDV}, title = {Rethinking neurodegenerative diseases: neurometabolic concept linking lipid oxidation to diseases in the central nervous system.}, journal = {Neural regeneration research}, volume = {19}, number = {7}, pages = {1437-1445}, pmid = {38051885}, issn = {1673-5374}, abstract = {Currently, there is a lack of effective medicines capable of halting or reversing the progression of neurodegenerative disorders, including amyotrophic lateral sclerosis, Parkinson's disease, multiple sclerosis, or Alzheimer's disease. Given the unmet medical need, it is necessary to reevaluate the existing paradigms of how to target these diseases. When considering neurodegenerative diseases from a systemic neurometabolic perspective, it becomes possible to explain the shared pathological features. This innovative approach presented in this paper draws upon extensive research conducted by the authors and researchers worldwide. In this review, we highlight the importance of metabolic mitochondrial dysfunction in the context of neurodegenerative diseases. We provide an overview of the risk factors associated with developing neurodegenerative disorders, including genetic, epigenetic, and environmental factors. Additionally, we examine pathological mechanisms implicated in these diseases such as oxidative stress, accumulation of misfolded proteins, inflammation, demyelination, death of neurons, insulin resistance, dysbiosis, and neurotransmitter disturbances. Finally, we outline a proposal for the restoration of mitochondrial metabolism, a crucial aspect that may hold the key to facilitating curative therapeutic interventions for neurodegenerative disorders in forthcoming advancements.}, } @article {pmid38051870, year = {2024}, author = {Hartopp, N and Markovinovic, A and Miller, CC and Gomez-Suaga, P}, title = {Insight into endoplasmic reticulum-mitochondria contacts in human amyotrophic lateral sclerosis.}, journal = {Neural regeneration research}, volume = {19}, number = {7}, pages = {1407-1408}, pmid = {38051870}, issn = {1673-5374}, support = {MR/R022666/1/MRC_/Medical Research Council/United Kingdom ; }, } @article {pmid38050971, year = {2024}, author = {Shellikeri, S and Cho, S and Ash, S and Gonzalez-Recober, C and Mcmillan, CT and Elman, L and Quinn, C and Amado, DA and Baer, M and Irwin, DJ and Massimo, L and Olm, CA and Liberman, MY and Grossman, M and Nevler, N}, title = {Digital markers of motor speech impairments in spontaneous speech of patients with ALS-FTD spectrum disorders.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {25}, number = {3-4}, pages = {317-325}, pmid = {38050971}, issn = {2167-9223}, support = {K99 AG073510/AG/NIA NIH HHS/United States ; P01 AG066597/AG/NIA NIH HHS/United States ; R01 NS109260/NS/NINDS NIH HHS/United States ; K08 NS114106/NS/NINDS NIH HHS/United States ; P30 AG072979/AG/NIA NIH HHS/United States ; R01 AG054519/AG/NIA NIH HHS/United States ; }, mesh = {Humans ; *Frontotemporal Dementia/diagnosis/diagnostic imaging ; *Amyotrophic Lateral Sclerosis/complications/diagnosis ; Speech ; Magnetic Resonance Imaging ; *Dystonic Disorders ; }, abstract = {OBJECTIVE: To evaluate automated digital speech measures, derived from spontaneous speech (picture descriptions), in assessing bulbar motor impairments in patients with ALS-FTD spectrum disorders (ALS-FTSD).

METHODS: Automated vowel algorithms were employed to extract two vowel acoustic measures: vowel space area (VSA), and mean second formant slope (F2 slope). Vowel measures were compared between ALS with and without clinical bulbar symptoms (ALS + bulbar (n = 49, ALSFRS-r bulbar subscore: x¯ = 9.8 (SD = 1.7)) vs. ALS-nonbulbar (n = 23), behavioral variant frontotemporal dementia (bvFTD, n = 25) without a motor syndrome, and healthy controls (HC, n = 32). Correlations with bulbar motor clinical scales, perceived listener effort, and MRI cortical thickness of the orobuccal primary motor cortex (oral PMC) were examined. We compared vowel measures to speaking rate, a conventional metric for assessing bulbar dysfunction.

RESULTS: ALS + bulbar had significantly reduced VSA and F2 slope than ALS-nonbulbar (|d|=0.94 and |d|=1.04, respectively), bvFTD (|d|=0.89 and |d|=1.47), and HC (|d|=0.73 and |d|=0.99). These reductions correlated with worse bulbar clinical scores (VSA: R = 0.33, p = 0.043; F2 slope: R = 0.38, p = 0.011), greater listener effort (VSA: R=-0.43, p = 0.041; F2 slope: p > 0.05), and cortical thinning in oral PMC (F2 slope: β = 0.0026, p = 0.017). Vowel measures demonstrated greater sensitivity and specificity for bulbar impairment than speaking rate, while showing independence from cognitive and respiratory impairments.

CONCLUSION: Automatic vowel measures are easily derived from a brief spontaneous speech sample, are sensitive to mild-moderate stage of bulbar disease in ALS-FTSD, and may present better sensitivity to bulbar impairment compared to traditional assessments such as speaking rate.}, } @article {pmid38050862, year = {2023}, author = {Liu, X and Duan, S and Jin, Y and Walker, E and Tsao, M and Jang, JH and Chen, Z and Singh, AK and Cantrell, KL and Ingolfsson, HI and Buratto, SK and Bowers, MT}, title = {Computationally Designed Molecules Modulate ALS-Related Amyloidogenic TDP-43307-319 Aggregation.}, journal = {ACS chemical neuroscience}, volume = {14}, number = {24}, pages = {4395-4408}, doi = {10.1021/acschemneuro.3c00582}, pmid = {38050862}, issn = {1948-7193}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy/metabolism ; *Frontotemporal Dementia ; *Frontotemporal Lobar Degeneration ; *Alzheimer Disease ; DNA-Binding Proteins/metabolism ; }, abstract = {Abnormal cytosolic aggregation of TAR DNA-binding protein of 43 kDa (TDP-43) is observed in multiple diseases, including amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration, and Alzheimer's disease. Previous studies have shown that TDP-43307-319 located at the C-terminal of TDP-43 can form higher-order oligomers and fibrils. Of particular interest are the hexamers that adopt a cylindrin structure that has been strongly correlated to neurotoxicity. In this study, we use the joint pharmacophore space (JPS) model to identify and generate potential TDP-43 inhibitors. Five JPS-designed molecules are evaluated using both experimental and computational methods: ion mobility mass spectrometry, thioflavin T fluorescence assay, circular dichroism spectroscopy, atomic force microscopy, and molecular dynamics simulations. We found that all five molecules can prevent the amyloid fibril formation of TDP-43307-319, but their efficacy varies significantly. Furthermore, among the five molecules, [AC0101] is the most efficient in preventing the formation of higher-order oligomers and dissociating preformed higher-order oligomers. Molecular dynamics simulations show that [AC0101] both is the most flexible and forms the most hydrogen bonds with the TDP-43307-319 monomer. The JPS-designed molecules can insert themselves between the β-strands in the hexameric cylindrin structure of TDP-43307-319 and can open its structure. Possible mechanisms for JPS-designed molecules to inhibit and dissociate TDP-43307-319 oligomers on an atomistic scale are proposed.}, } @article {pmid38050178, year = {2024}, author = {Megens, M and de Souza, A}, title = {Amyotrophic lateral sclerosis with demyelinating neurophysiology and a motor band sign.}, journal = {Practical neurology}, volume = {24}, number = {3}, pages = {219-222}, doi = {10.1136/pn-2023-003963}, pmid = {38050178}, issn = {1474-7766}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology/diagnosis ; Male ; Aged ; Neural Conduction/physiology ; Polyradiculoneuropathy, Chronic Inflammatory Demyelinating/physiopathology/diagnosis/diagnostic imaging ; Magnetic Resonance Imaging/methods ; Demyelinating Diseases/diagnostic imaging/physiopathology ; }, abstract = {We describe an unusual case of clinical amyotrophic lateral sclerosis (ALS) with initial neurophysiological studies suggesting demyelination, along with neuroimaging findings that helped to support the eventual diagnosis. An otherwise well 68-year-old man had 8 weeks of left upper limb weakness. On examination, there were widespread lower and upper motor neurone findings suggesting ALS. However, nerve conduction studies identified sensorimotor demyelinating changes suggesting chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), a diagnosis further supported by cerebrospinal fluid analysis. MR scan of the brain revealed a 'motor band', a feature seen commonly in ALS. His condition was refractory to immunotherapy with clinical progression in-keeping with ALS, establishing the diagnosis. ALS is rarely associated with demyelinating neurophysiological changes resembling CIDP. The clinical phenotype is crucial to support the correct diagnosis and imaging findings may help.}, } @article {pmid38050140, year = {2024}, author = {Thompson, AG and Taschler, B and Smith, SM and Turner, MR}, title = {Premorbid brain structure influences risk of amyotrophic lateral sclerosis.}, journal = {Journal of neurology, neurosurgery, and psychiatry}, volume = {95}, number = {4}, pages = {360-365}, pmid = {38050140}, issn = {1468-330X}, support = {/WT_/Wellcome Trust/United Kingdom ; TURNER/OCT18/989-797/MNDA_/Motor Neurone Disease Association/United Kingdom ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnostic imaging/genetics ; Brain/diagnostic imaging ; Gray Matter/diagnostic imaging ; Magnetic Resonance Imaging ; *White Matter/diagnostic imaging ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a disease of the motor network associated with brain structure and functional connectivity alterations that are implicated in disease progression. Whether such changes have a causal role in ALS, fitting with a postulated influence of premorbid cerebral architecture on the phenotypes associated with neurodegenerative disorders is not known.

METHODS: This study considered causal effects and shared genetic risk of 2240 structural and functional MRI brain scan imaging-derived phenotypes (IDPs) on ALS using two sample Mendelian randomisation, with putative associations further examined with extensive sensitivity analysis. Shared genetic predisposition between IDPs and ALS was explored using genetic correlation analysis.

RESULTS: Increased white matter volume in the cerebral hemispheres was causally associated with ALS. Weaker causal associations were observed for brain stem grey matter volume, parieto-occipital white matter surface and volume of the left thalamic ventral anterior nucleus. Genetic correlation was observed between ALS and intracellular volume fraction and isotropic free water volume fraction within the posterior limb of the internal capsule.

CONCLUSIONS: This study provides evidence that premorbid brain structure, in particular white matter volume, contributes to the risk of ALS.}, } @article {pmid38050066, year = {2024}, author = {Bowser, R and An, J and Mehta, L and Chen, J and Timmons, J and Cudkowicz, M and Paganoni, S}, title = {Effect of sodium phenylbutyrate and taurursodiol on plasma concentrations of neuroinflammatory biomarkers in amyotrophic lateral sclerosis: results from the CENTAUR trial.}, journal = {Journal of neurology, neurosurgery, and psychiatry}, volume = {95}, number = {7}, pages = {605-608}, pmid = {38050066}, issn = {1468-330X}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/blood/drug therapy ; *Biomarkers/blood ; *Chitinase-3-Like Protein 1/blood ; *C-Reactive Protein/analysis ; *Phenylbutyrates/therapeutic use ; Female ; Male ; Middle Aged ; Hexosaminidases/blood ; Aged ; Double-Blind Method ; Chitinases/blood ; }, abstract = {BACKGROUND: An oral sodium phenylbutyrate and taurursodiol combination (PB and TURSO) significantly reduced functional decline in people living with amyotrophic lateral sclerosis (ALS) in the CENTAUR trial. Biomarkers linking clinical therapeutic effect with biological changes are of high interest in ALS. We performed analyses of neuroinflammatory biomarkers associated with ALS in the literature, including YKL-40 (also known as chitinase-3-like protein 1), chitinase 1 (CHIT1) and C reactive protein (CRP), in plasma samples collected in CENTAUR.

METHODS: Log10-transformed plasma biomarker measurements were analysed using a linear mixed-effects model. Correlation between paired biomarker concentrations and ALS Functional Rating Scale-Revised (ALSFRS-R) total scores was assessed via Pearson correlation coefficients.

RESULTS: By week 24, geometric least squares mean YKL-40 plasma concentration decreased by approximately 20% (p=0.008) and CRP by 30% (p=0.048) in the PB and TURSO versus placebo group. YKL-40 (r of -0.21; p<0.0001) and CRP (r of -0.19; p=0.0002) concentration correlated with ALSFRS-R total score. CHIT1 levels were not significantly different between groups.

CONCLUSIONS: YKL-40 and CRP plasma levels were significantly reduced in participants with ALS receiving PB and TURSO in CENTAUR and correlated with disease progression. These findings suggest YKL-40 and CRP could be treatment-sensitive biomarkers in ALS, pending further confirmatory studies.

TRIAL REGISTRATION NUMBER: https://clinicaltrials.gov/study/NCT03127514.}, } @article {pmid38049694, year = {2024}, author = {Sequeira, M and Godinho, F and Lourenço, J}, title = {Amyotrophic Lateral Sclerosis with SOD1 Mutation Presenting with Progressive Cerebellar Ataxia.}, journal = {Cerebellum (London, England)}, volume = {23}, number = {4}, pages = {1702-1704}, pmid = {38049694}, issn = {1473-4230}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/pathology ; *Superoxide Dismutase-1/genetics ; *Cerebellar Ataxia/genetics/diagnostic imaging ; *Mutation ; *Superoxide Dismutase/genetics ; Male ; Middle Aged ; Female ; }, abstract = {Amyotrophic lateral sclerosis is a fatal neurodegenerative disorder that affects upper and lower motor neurons. SOD1 mutations are the second most commonly found in familial and sporadic cases. We describe a patient with a homozygous pathogenic mutation in SOD1 gene that presented with a progressive cerebellar ataxia and ultimately developed a complex phenotype of cerebellar ataxia and motor neuron disease. The linkage between the cerebellum and ALS is shortly discussed.}, } @article {pmid38049641, year = {2024}, author = {Kiani, L}, title = {ALS pathogenesis linked to actin barrier collapse.}, journal = {Nature reviews. Neurology}, volume = {20}, number = {1}, pages = {1}, pmid = {38049641}, issn = {1759-4766}, mesh = {Humans ; *Actins ; *Amyotrophic Lateral Sclerosis/etiology ; }, } @article {pmid38049549, year = {2024}, author = {Wu, T and Li, H}, title = {A case of Mills' syndrome: initially characterized by one cerebral hemisphere atrophy and decreased brain metabolism then evolving into amyotrophic lateral sclerosis.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {45}, number = {3}, pages = {1311-1313}, pmid = {38049549}, issn = {1590-3478}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/complications/diagnostic imaging/pathology ; *Motor Neuron Disease ; Brain/diagnostic imaging/pathology ; Chronic Disease ; Atrophy/pathology ; Muscular Atrophy ; *Cerebrum ; }, abstract = {This article reports a case of Mills' syndrome that initially manifested as atrophy of one cerebral hemisphere and decreased brain metabolism, which developed into amyotrophic lateral sclerosis in the fourth year of the disease. Mills' syndrome is a rare type of motor neuron disease, with only over 20 cases reported since 1990, but most lack imaging such as PET and DTI. This article provides a complete report of the 18F-FDG-PET and DTI images consistent with the characteristics of Mills' syndrome. In addition, we have discovered some new phenomena, which have certain clinical and teaching values. Firstly, the frontal, parietal and temporal lobes on the side of the lesion in the pyramidal tract of this patient were significantly atrophic, indicating that unilateral brain lobe atrophy may be a new feature of Mills' syndrome. Secondly, although there were no abnormalities in three EMG tests taken during the 4 years prior to the onset of the disease, amyotrophy and ALS-like EMG features appeared in the fourth year, suggesting that some Mills' syndrome may progress more rapidly to ALS. This highlights the importance of regular follow-up electromyography in Mills' syndrome patients.}, } @article {pmid38049418, year = {2023}, author = {Megat, S and Mora, N and Sanogo, J and Roman, O and Catanese, A and Alami, NO and Freischmidt, A and Mingaj, X and De Calbiac, H and Muratet, F and Dirrig-Grosch, S and Dieterle, S and Van Bakel, N and Müller, K and Sieverding, K and Weishaupt, J and Andersen, PM and Weber, M and Neuwirth, C and Margelisch, M and Sommacal, A and Van Eijk, KR and Veldink, JH and , and Lautrette, G and Couratier, P and Camuzat, A and Le Ber, I and Grassano, M and Chio, A and Boeckers, T and Ludolph, AC and Roselli, F and Yilmazer-Hanke, D and Millecamps, S and Kabashi, E and Storkebaum, E and Sellier, C and Dupuis, L}, title = {Author Correction: Integrative genetic analysis illuminates ALS heritability and identifies risk genes.}, journal = {Nature communications}, volume = {14}, number = {1}, pages = {8026}, doi = {10.1038/s41467-023-43710-4}, pmid = {38049418}, issn = {2041-1723}, } @article {pmid38049069, year = {2024}, author = {Navarro-Fernandez, I}, title = {Tracing the origins of setons in hidradenitis suppurativa: A commentary to Vilarrasa et al's "Drainage setons for the management of sinus tracts in hidradenitis suppurativa".}, journal = {Journal of the American Academy of Dermatology}, volume = {90}, number = {4}, pages = {e139}, doi = {10.1016/j.jaad.2023.10.068}, pmid = {38049069}, issn = {1097-6787}, mesh = {Humans ; *Hidradenitis Suppurativa ; Inflammation ; }, } @article {pmid38049068, year = {2024}, author = {Wang, B and Huang, Y and Li, J}, title = {Response to John et al's comments of "paroxetine is an effective treatment for refractory erythema of rosacea: Primary results from the prospective rosacea refractory erythema randomized clinical trial".}, journal = {Journal of the American Academy of Dermatology}, volume = {90}, number = {4}, pages = {e143-e144}, doi = {10.1016/j.jaad.2023.11.050}, pmid = {38049068}, issn = {1097-6787}, mesh = {Humans ; *Paroxetine/therapeutic use ; Prospective Studies ; *Rosacea/drug therapy ; Erythema/drug therapy/etiology ; Treatment Outcome ; }, } @article {pmid38046608, year = {2023}, author = {Wang, R and Sun, Y and Lan, Y and Wei, S and Huang, H and Li, X and Huang, Z}, title = {ALS gene overexpression and enhanced metabolism conferring Digitaria sanguinalis resistance to nicosulfuron in China.}, journal = {Frontiers in plant science}, volume = {14}, number = {}, pages = {1290600}, pmid = {38046608}, issn = {1664-462X}, abstract = {Crabgrass (Digitaria sanguinalis) is a common malignant weed in corn fields in China. Recently, the acetolactate synthase (ALS) inhibitor, nicosulfuron, has shown decreasing efficacy against crabgrass. In order to elucidate the molecular basis of resistance to nicosulfuron in crabgrass, we conducted bioassays, combined with gene sequence analysis, relative expression and relative copy number analysis, to characterize resistance in crabgrass populations collected from Beijing, Heilongjiang, Jilin and Anhui provinces. Whole-plant dose-response results indicated that only population collected in Heilongjiang province (HLJ) had developed low level of resistance to nicosulfuron compared with the sensitive population (SD22). No known resistant mutation of ALS gene was found in HLJ population. The real-time fluorescence quantitative PCR results showed that the ALS gene copy number did not differ significantly between the HLJ and SD22 populations. However, the ALS gene expression in the HLJ was 2.07-fold higher than that of the SD22 population at 24 h after treatment with nicosulfuron. Pretreatment with the cytochrome P450 (CYP450) inhibitor malathion, piperonyl butoxide (PBO), and the glutathione S-transferase (GST) inhibitor 4-Chloro-7-nitro-1,2,3-benzoxadiazole (NBD-Cl) all partially reversed HLJ resistance. Among them, the synergistic effect of PBO and nicosulfuron is the most significant. This is the first report of resistance to nicosulfuron in crabgrass through ALS gene overexpression and possible metabolic resistance.}, } @article {pmid38046601, year = {2023}, author = {Quan, W and Chan, Z and Wei, P and Mao, Y and Bartels, D and Liu, X}, title = {PHD finger proteins function in plant development and abiotic stress responses: an overview.}, journal = {Frontiers in plant science}, volume = {14}, number = {}, pages = {1297607}, pmid = {38046601}, issn = {1664-462X}, abstract = {The plant homeodomain (PHD) finger with a conserved Cys4-His-Cys3 motif is a common zinc-binding domain, which is widely present in all eukaryotic genomes. The PHD finger is the "reader" domain of methylation marks in histone H3 and plays a role in the regulation of gene expression patterns. Numerous proteins containing the PHD finger have been found in plants. In this review, we summarize the functional studies on PHD finger proteins in plant growth and development and responses to abiotic stresses in recent years. Some PHD finger proteins, such as VIN3, VILs, and Ehd3, are involved in the regulation of flowering time, while some PHD finger proteins participate in the pollen development, for example, MS, TIP3, and MMD1. Furthermore, other PHD finger proteins regulate the plant tolerance to abiotic stresses, including Alfin1, ALs, and AtSIZ1. Research suggests that PHD finger proteins, as an essential transcription regulator family, play critical roles in various plant biological processes, which is helpful in understanding the molecular mechanisms of novel PHD finger proteins to perform specific function.}, } @article {pmid38046408, year = {2023}, author = {Liu, J and Li, H and Zhou, Y and Zhang, Y and Song, S and Gu, X and Xu, J and Yu, X}, title = {Deep learning-based estimation of axial length using macular optical coherence tomography images.}, journal = {Frontiers in medicine}, volume = {10}, number = {}, pages = {1308923}, pmid = {38046408}, issn = {2296-858X}, abstract = {BACKGROUND: This study aimed to develop deep learning models using macular optical coherence tomography (OCT) images to estimate axial lengths (ALs) in eyes without maculopathy.

METHODS: A total of 2,664 macular OCT images from 444 patients' eyes without maculopathy, who visited Beijing Hospital between March 2019 and October 2021, were included. The dataset was divided into training, validation, and testing sets with a ratio of 6:2:2. Three pre-trained models (ResNet 18, ResNet 50, and ViT) were developed for binary classification (AL ≥ 26 mm) and regression task. Ten-fold cross-validation was performed, and Grad-CAM analysis was employed to visualize AL-related macular features. Additionally, retinal thickness measurements were used to predict AL by linear and logistic regression models.

RESULTS: ResNet 50 achieved an accuracy of 0.872 (95% Confidence Interval [CI], 0.840-0.899), with high sensitivity of 0.804 (95% CI, 0.728-0.867) and specificity of 0.895 (95% CI, 0.861-0.923). The mean absolute error for AL prediction was 0.83 mm (95% CI, 0.72-0.95 mm). The best AUC, and accuracy of AL estimation using macular OCT images (0.929, 87.2%) was superior to using retinal thickness measurements alone (0.747, 77.8%). AL-related macular features were on the fovea and adjacent regions.

CONCLUSION: OCT images can be effectively utilized for estimating AL with good performance via deep learning. The AL-related macular features exhibit a localized pattern in the macula, rather than continuous alterations throughout the entire region. These findings can lay the foundation for future research in the pathogenesis of AL-related maculopathy.}, } @article {pmid38045991, year = {2023}, author = {Barberio, J and Lally, C and Kupelian, V and Hardiman, O and Flanders, WD}, title = {Estimated Familial Amyotrophic Lateral Sclerosis Proportion: A Literature Review and Meta-analysis.}, journal = {Neurology. Genetics}, volume = {9}, number = {6}, pages = {e200109}, pmid = {38045991}, issn = {2376-7839}, abstract = {BACKGROUND AND OBJECTIVES: Amyotrophic lateral sclerosis (ALS) is a rare neurodegenerative disorder. Familial (fALS) cases are usually reported to constitute 5%-10% of all ALS cases; however, no recent literature review or meta-analysis of this proportion (referred to throughout as "proportion fALS") has been conducted. Our objective was to estimate the proportion fALS by geographic region and to assess the effect of study characteristics on the estimates.

METHODS: A comprehensive literature review was performed to identify all original studies reporting the number of fALS cases in an ALS cohort. The results were stratified by geographic region, study design (case series or population-based), and decade of study publication. Subgroup analyses were conducted according to family history criteria used to define fALS. We report pooled estimates of the proportion fALS from random-effects meta-analyses when >2 studies are available and I[2] is < 90%; weighted averages and ranges are otherwise presented.

RESULTS: The overall pooled proportion fALS based on a total 165 studies was 8% (0%, 71%). The proportion fALS was 9% (0%, 71%) among 107 case series and 5% (4%, 6%) among 58 population-based studies. Among population-based studies, proportion fALS by geographic region was 6% (5%, 7%; N = 37) for Europe, 5% (3%, 7%; N = 5) for Latin America, and 5% (4%, 7%; N = 12) for North America. Criteria used to define fALS were reported by 21 population-based studies (36%), and proportion fALS was 5% (4%, 5%; N = 9) for first-degree relative, 7% (4%, 11%; N = 4) for first or second-degree relative, and 11% (N = 1) for more distant ALS family history. Population-based studies published in the 2000s or earlier generated a lower pooled proportion fALS than studies published in the 2010s or later.

DISCUSSION: The results suggest that variability in the reported proportion fALS in the literature may be, in part, due to the differences in geography, study design, fALS definition, and decade of case ascertainment. Few studies outside of European ancestral populations were available. The proportion fALS was marginally higher among case series compared with population-based studies, likely because of referral bias. Criteria used to define fALS were largely unreported. Consensus criteria for fALS and additional population-based studies in non-European ancestral populations are needed.}, } @article {pmid38043854, year = {2024}, author = {Pourzand, P and Moore, J and Metzger, A and Salverda, B and Suresh, M and Arango, S and Rosenhagen, H and Kaizer, A and Duval, S and Debaty, G and Lurie, K}, title = {Hemodynamics, survival and neurological function with early versus delayed automated head-up CPR in a porcine model of prolonged cardiac arrest.}, journal = {Resuscitation}, volume = {194}, number = {}, pages = {110067}, doi = {10.1016/j.resuscitation.2023.110067}, pmid = {38043854}, issn = {1873-1570}, support = {R43HL158361/NH/NIH HHS/United States ; }, mesh = {Animals ; *Cardiopulmonary Resuscitation/methods ; Disease Models, Animal ; Epinephrine ; *Heart Arrest ; Hemodynamics ; Swine ; }, abstract = {AIM: To determine if controlled head and thorax elevation, active compression-decompression cardiopulmonary resuscitation (CPR), and an impedance threshold device combined, termed automated head-up positioning CPR (AHUP-CPR), should be initiated early, as a basic (BLS) intervention, or later, as an advanced (ALS) intervention, in a severe porcine model of cardiac arrest.

METHODS: Yorkshire pigs (n = 22) weighing ∼40 kg were anesthetized and ventilated. After 15 minutes of untreated ventricular fibrillation, pigs were randomized to AHUP-CPR for 25 minutes (BLS group) or conventional CPR for 10 minutes, followed by 15 minutes of AHUP-CPR (ALS group). Thereafter, epinephrine, amiodarone, and defibrillation were administered. Neurologic function, the primary endpoint, was assessed 24-hours later with a Neurological Deficit Score (NDS, 0 = normal and 260 = worst deficit score or death). Secondary outcomes included return of spontaneous circulation (ROSC), cumulative survival, hemodynamics and epinephrine responsivity. Data, expressed as mean ± standard deviation, were compared using Fisher's Exact, log-rank, Mann-Whitney U and unpaired t-tests.

RESULTS: ROSC was achieved in 10/11 pigs with early AHUP-CPR versus 6/11 with delayed AHUP-CPR (p = 0.14), and cumulative 24-hour survival was 45.5% versus 9.1%, respectively (p < 0.02). The NDS was 203 ± 80 with early AHUP-CPR versus 259 ± 3 with delayed AHUP-CPR (p = 0.035). ETCO2, rSO2, and responsiveness to epinephrine were significantly higher in the early versus delayed AHUP-CPR.

CONCLUSION: When delivered early rather than late, AHUP-CPR resulted in significantly increased hemodynamics, 24-hour survival, and improved neurological function in pigs after prolonged cardiac arrest. Based on these findings, AHUP-CPR should be considered a BLS intervention.}, } @article {pmid38043051, year = {2024}, author = {Graber, DJ and Cook, WJ and Sentman, ML and Murad-Mabaera, JM and Sentman, CL}, title = {Human CD4+CD25+ T cells expressing a chimeric antigen receptor against aberrant superoxide dismutase 1 trigger antigen-specific immunomodulation.}, journal = {Cytotherapy}, volume = {26}, number = {2}, pages = {126-135}, pmid = {38043051}, issn = {1477-2566}, support = {P30 CA023108/CA/NCI NIH HHS/United States ; R21 NS102556/NS/NINDS NIH HHS/United States ; R21 NS117895/NS/NINDS NIH HHS/United States ; }, mesh = {Mice ; Animals ; Humans ; Superoxide Dismutase-1/genetics/metabolism/therapeutic use ; *Amyotrophic Lateral Sclerosis/genetics/therapy ; *Receptors, Chimeric Antigen/therapeutic use ; Interleukin-10/genetics ; Superoxide Dismutase/metabolism ; Mice, Transgenic ; CD4-Positive T-Lymphocytes/metabolism ; Immunomodulation ; Disease Models, Animal ; }, abstract = {BACKGROUND AIMS: Amyotrophic lateral sclerosis (ALS) is a fatal disease associated with motor neuron degeneration, accumulation of aggregated misfolded proteins and neuroinflammation in motor regions of the central nervous system (CNS). Clinical trials using regulatory T cells (Tregs) are ongoing because of Tregs' immunomodulatory function, ability to traffic to the CNS, high numbers correlating with slower disease in ALS and disease-modifying activity in ALS mouse models. In the current study, a chimeric antigen receptor (CAR) was developed and characterized in human Tregs to enhance their immunomodulatory activity when in contact with an ALS protein aggregate.

METHODS: A CAR (DG05-28-3z) consisting of a human superoxide dismutase 1 (hSOD1)-binding single-chain variable fragment, CD28 hinge, transmembrane and co-stimulatory domain and CD3ζ signaling domain was created and expressed in human Tregs. Human Tregs were isolated by either magnetic enrichment for CD4+CD25[hi] cells (Enr-Tregs) or cell sorting for CD4+CD25[hi]CD127[lo] cells (FP-Tregs), transduced and expanded for 17 days.

RESULTS: The CAR bound preferentially to the ALS mutant G93A-hSOD1 protein relative to the wild-type hSOD1 protein. The CAR Tregs produced IL-10 when cultured with aggregated G93A-hSOD1 proteins or spinal cord explants from G93A-hSOD1 transgenic mice. Co-culturing DG05-28-3z CAR Tregs with human monocytes/macrophages inhibited production of tumor necrosis factor alpha and reactive oxygen species. Expanded FP-Tregs resulted in more robust Tregs compared with Enr-Tregs. FP-Tregs produced similar IL-10 and less interferon gamma, had lower Treg-specific demethylated region methylation and expressed higher FoxP3 and CD39.

CONCLUSIONS: Taken together, this study demonstrates that gene-modified Tregs can be developed to target an aggregated ALS-relevant protein to elicit CAR-mediated Treg effector functions and provides an approach for generating Treg therapies for ALS with the goal of enhanced disease site-specific immunomodulation.}, } @article {pmid38042502, year = {2024}, author = {Ma, H and Huo, J and Xin, C and Yang, J and Liu, Q and Dong, H and Li, R and Liu, Y}, title = {RABGGTB plays a critical role in ALS pathogenesis.}, journal = {Brain research bulletin}, volume = {206}, number = {}, pages = {110833}, doi = {10.1016/j.brainresbull.2023.110833}, pmid = {38042502}, issn = {1873-2747}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism ; Superoxide Dismutase-1/genetics/metabolism ; *Neurodegenerative Diseases/metabolism ; Motor Neurons/metabolism ; Spinal Cord/metabolism ; DNA-Binding Proteins/metabolism ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease with unknown causes, which mainly affects motor neurons in the anterior horn of the spinal cord, brain stem, and cerebral cortex, also known as motor neuron disease. An important pathological feature of ALS is the formation of aggregates of mutant SOD1 protein, CTF25 of TDP-43, or other abnormal proteins in motor neurons, which require autophagy for degradation. Protein prenylation is known to participate in membrane association and proper localization of proteins. RABGGTB is the β subunit of GGTase II (one of the prenyltransferases) that can regulate autophagy via Rab7 geranylgeranylation. In this study, we overexpressed RABGGTB via lentiviral transfection in NSC34-hSOD1G93A and TDP-43 cells. Overexpression of RABGGTB improved ALS cell proliferation by facilitating autophagosome-lysosome fusion. Furthermore, the abnormal aggregation of SOD1 protein was reduced. This indicates that protein prenylation is important for the proliferation and autophagy of cells autophagy. Enhanced autophagy has been observed in two of the most widely used ALS cell models. These findings indicate the widespread applicability of prenylation in ALS. In summary, overexpression of RABGGTB improved the geranylgeranylation of the Rab7 protein and had a positive effect on cells. These findings provide insights into the development of a novel therapeutic strategy for ALS.}, } @article {pmid38041684, year = {2024}, author = {Dohrn, MF and Beijer, D and Lone, MA and Bayraktar, E and Oflazer, P and Orbach, R and Donkervoort, S and Foley, AR and Rose, A and Lyons, M and Louie, RJ and Gable, K and Dunn, T and Chen, S and Danzi, MC and Synofzik, M and Bönnemann, CG and Nazlı Başak, A and Hornemann, T and Zuchner, S}, title = {Recurrent de-novo gain-of-function mutation in SPTLC2 confirms dysregulated sphingolipid production to cause juvenile amyotrophic lateral sclerosis.}, journal = {Journal of neurology, neurosurgery, and psychiatry}, volume = {95}, number = {3}, pages = {201-205}, pmid = {38041684}, issn = {1468-330X}, support = {R01 NS072248/NS/NINDS NIH HHS/United States ; R01 NS105755/NS/NINDS NIH HHS/United States ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics ; Ceramides ; Gain of Function Mutation ; Mutation/genetics ; *Serine C-Palmitoyltransferase/genetics/chemistry ; Sphingolipids ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) leads to paralysis and death by progressive degeneration of motor neurons. Recently, specific gain-of-function mutations in SPTLC1 were identified in patients with juvenile form of ALS. SPTLC2 encodes the second catalytic subunit of the serine-palmitoyltransferase (SPT) complex.

METHODS: We used the GENESIS platform to screen 700 ALS whole-genome and whole-exome data sets for variants in SPTLC2. The de-novo status was confirmed by Sanger sequencing. Sphingolipidomics was performed using liquid chromatography and high-resolution mass spectrometry.

RESULTS: Two unrelated patients presented with early-onset progressive proximal and distal muscle weakness, oral fasciculations, and pyramidal signs. Both patients carried the novel de-novo SPTLC2 mutation, c.203T>G, p.Met68Arg. This variant lies within a single short transmembrane domain of SPTLC2, suggesting that the mutation renders the SPT complex irresponsive to regulation through ORMDL3. Confirming this hypothesis, ceramide and complex sphingolipid levels were significantly increased in patient plasma. Accordingly, excessive sphingolipid production was shown in mutant-expressing human embryonic kindney (HEK) cells.

CONCLUSIONS: Specific gain-of-function mutations in both core subunits affect the homoeostatic control of SPT. SPTLC2 represents a new Mendelian ALS gene, highlighting a key role of dysregulated sphingolipid synthesis in the pathogenesis of juvenile ALS. Given the direct interaction of SPTLC1 and SPTLC2, this knowledge might open new therapeutic avenues for motor neuron diseases.}, } @article {pmid38041679, year = {2024}, author = {Syeda, SB and Lone, MA and Mohassel, P and Donkervoort, S and Munot, P and França, MC and Galarza-Brito, JE and Eckenweiler, M and Asamoah, A and Gable, K and Majumdar, A and Schumann, A and Gupta, SD and Lakhotia, A and Shieh, PB and Foley, AR and Jackson, KE and Chao, KR and Winder, TL and Catapano, F and Feng, L and Kirschner, J and Muntoni, F and Dunn, TM and Hornemann, T and Bönnemann, CG}, title = {Recurrent de novo SPTLC2 variant causes childhood-onset amyotrophic lateral sclerosis (ALS) by excess sphingolipid synthesis.}, journal = {Journal of neurology, neurosurgery, and psychiatry}, volume = {95}, number = {2}, pages = {103-113}, pmid = {38041679}, issn = {1468-330X}, support = {R01 HG009141/HG/NHGRI NIH HHS/United States ; UM1 HG008900/HG/NHGRI NIH HHS/United States ; }, mesh = {Child ; Humans ; *Amyotrophic Lateral Sclerosis/genetics ; *Neurodegenerative Diseases ; Sphingolipids ; Serine C-Palmitoyltransferase/genetics/metabolism ; *Hereditary Sensory and Autonomic Neuropathies/genetics ; Serine ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease of the upper and lower motor neurons with varying ages of onset, progression and pathomechanisms. Monogenic childhood-onset ALS, although rare, forms an important subgroup of ALS. We recently reported specific SPTLC1 variants resulting in sphingolipid overproduction as a cause for juvenile ALS. Here, we report six patients from six independent families with a recurrent, de novo, heterozygous variant in SPTLC2 c.778G>A [p.Glu260Lys] manifesting with juvenile ALS.

METHODS: Clinical examination of the patients along with ancillary and genetic testing, followed by biochemical investigation of patients' blood and fibroblasts, was performed.

RESULTS: All patients presented with early-childhood-onset progressive weakness, with signs and symptoms of upper and lower motor neuron degeneration in multiple myotomes, without sensory neuropathy. These findings were supported on ancillary testing including nerve conduction studies and electromyography, muscle biopsies and muscle ultrasound studies. Biochemical investigations in plasma and fibroblasts showed elevated levels of ceramides and unrestrained de novo sphingolipid synthesis. Our studies indicate that SPTLC2 variant [c.778G>A, p.Glu260Lys] acts distinctly from hereditary sensory and autonomic neuropathy (HSAN)-causing SPTLC2 variants by causing excess canonical sphingolipid biosynthesis, similar to the recently reported SPTLC1 ALS associated pathogenic variants. Our studies also indicate that serine supplementation, which is a therapeutic in SPTLC1 and SPTCL2-associated HSAN, is expected to exacerbate the excess sphingolipid synthesis in serine palmitoyltransferase (SPT)-associated ALS.

CONCLUSIONS: SPTLC2 is the second SPT-associated gene that underlies monogenic, juvenile ALS and further establishes alterations of sphingolipid metabolism in motor neuron disease pathogenesis. Our findings also have important therapeutic implications: serine supplementation must be avoided in SPT-associated ALS, as it is expected to drive pathogenesis further.}, } @article {pmid38041669, year = {2024}, author = {Guissart, C and De la Cruz, E and Flabeau, O and Grapperon, AM and Corazza, G and Junilhon, L and Delmas, JC and Millecamps, S and Polge, A and Amador, MDM and Salachas, F and Rochat, J and Goizet, C and Juntas Morales, R and Lumbroso, S and Philibert, P and Cheillan, D and Mouzat, K}, title = {Heterozygous SPTLC1 p.Leu39del is a major cause of slow-progressing juvenile ALS.}, journal = {Journal of neurology, neurosurgery, and psychiatry}, volume = {95}, number = {3}, pages = {288-290}, doi = {10.1136/jnnp-2023-331753}, pmid = {38041669}, issn = {1468-330X}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics ; Mutation ; *Serine C-Palmitoyltransferase/genetics ; }, } @article {pmid38041662, year = {2024}, author = {Shy, ME}, title = {Genetics, cell biology and a novel mechanism for ALS.}, journal = {Journal of neurology, neurosurgery, and psychiatry}, volume = {95}, number = {3}, pages = {199-200}, doi = {10.1136/jnnp-2023-332720}, pmid = {38041662}, issn = {1468-330X}, mesh = {Humans ; Animals ; *Amyotrophic Lateral Sclerosis/genetics ; Motor Neurons ; Disease Models, Animal ; *Motor Neuron Disease ; }, } @article {pmid38041659, year = {2024}, author = {Kiernan, MC and Farrar, MA}, title = {Emerging role for sphingolipids in the genetics of amyotrophic lateral sclerosis.}, journal = {Journal of neurology, neurosurgery, and psychiatry}, volume = {95}, number = {2}, pages = {101-102}, doi = {10.1136/jnnp-2023-332719}, pmid = {38041659}, issn = {1468-330X}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics ; Sphingolipids ; *Motor Neuron Disease ; }, } @article {pmid38038225, year = {2024}, author = {Sanghani, N and Claytor, B and Li, Y}, title = {Electrodiagnostic findings in amyotrophic lateral sclerosis: Variation with region of onset and utility of thoracic paraspinal muscle examination.}, journal = {Muscle & nerve}, volume = {69}, number = {2}, pages = {172-178}, doi = {10.1002/mus.28012}, pmid = {38038225}, issn = {1097-4598}, mesh = {Humans ; Female ; Male ; *Amyotrophic Lateral Sclerosis/diagnosis ; Retrospective Studies ; Paraspinal Muscles ; Electromyography ; Electrodiagnosis ; }, abstract = {INTRODUCTION/AIMS: Limited data exist regarding variation of electrodiagnostic (EDX) findings in amyotrophic lateral sclerosis (ALS) patients with different onset regions and specificity of thoracic paraspinal muscle (TPSP) examination for confirming a diagnosis of ALS. We aimed to demonstrate the variation of EDX features and characterize the utility of TPSP muscle examination in the electrodiagnosis of ALS.

METHODS: This is a retrospective study of a large cohort of ALS patients who had a comprehensive EDX evaluation.

RESULTS: The study included 448 patients; all fulfilled the Gold Coast criteria for ALS. The average age at the time of EDX study was 64 years, and 41.1% were women. The onset region was identified as follows: bulbar (N = 149), cervical (N = 127), lumbosacral (N = 162), and other (N = 10). In contrast to limb onset, bulbar-onset patients more frequently demonstrated a pattern of normal or near normal needle electromyography (EMG) (p < .0001) and less frequently had abnormalities on EMG of TPSP (p = .002). Clinical or EDX diagnosis of sensory polyneuropathy was present in 12.6% patients, more frequently in the lumbosacral onset subgroup (p < .03). EMG showed active denervation in 9.6% and chronic denervation in 59% of craniobulbar muscles examined, without observed difference among different onset regions. TPSP showed higher frequencies of active and chronic denervation in ALS than a group of patients with non-ALS neuromuscular disorders.

DISCUSSION: EDX features may differ among ALS patients of different onset regions. TPSP EMG is highly useful in differentiating ALS from non-ALS neuromuscular disorders while the yield of craniobulbar muscles, especially for active denervation, is low.}, } @article {pmid38037913, year = {2024}, author = {Zhong, G and Wang, X and Li, J and Xie, Z and Wu, Q and Chen, J and Wang, Y and Chen, Z and Cao, X and Li, T and Liu, J and Wang, Q}, title = {Insights Into the Role of Copper in Neurodegenerative Diseases and the Therapeutic Potential of Natural Compounds.}, journal = {Current neuropharmacology}, volume = {22}, number = {10}, pages = {1650-1671}, pmid = {38037913}, issn = {1875-6190}, support = {81973918, 82274616//National Natural Science Foundation of China/ ; 2019KSYS005//Key laboratory project of colleges and universities in Guangdong Province/ ; 2020A0505100052//Guangdong province science and technology plan international cooperation project/ ; }, mesh = {Humans ; *Neurodegenerative Diseases/drug therapy/metabolism ; *Copper/metabolism ; Animals ; Biological Products/therapeutic use/pharmacology ; Homeostasis/drug effects ; Chelating Agents/therapeutic use/pharmacology ; }, abstract = {Neurodegenerative diseases encompass a collection of neurological disorders originating from the progressive degeneration of neurons, resulting in the dysfunction of neurons. Unfortunately, effective therapeutic interventions for these diseases are presently lacking. Copper (Cu), a crucial trace element within the human body, assumes a pivotal role in various biological metabolic processes, including energy metabolism, antioxidant defense, and neurotransmission. These processes are vital for the sustenance, growth, and development of organisms. Mounting evidence suggests that disrupted copper homeostasis contributes to numerous age-related neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), Wilson's disease (WD), Menkes disease (MD), prion diseases, and multiple sclerosis (MS). This comprehensive review investigates the connection between the imbalance of copper homeostasis and neurodegenerative diseases, summarizing pertinent drugs and therapies that ameliorate neuropathological changes, motor deficits, and cognitive impairments in these conditions through the modulation of copper metabolism. These interventions include Metal-Protein Attenuating Compounds (MPACs), copper chelators, copper supplements, and zinc salts. Moreover, this review highlights the potential of active compounds derived from natural plant medicines to enhance neurodegenerative disease outcomes by regulating copper homeostasis. Among these compounds, polyphenols are particularly abundant. Consequently, this review holds significant implications for the future development of innovative drugs targeting the treatment of neurodegenerative diseases.}, } @article {pmid38036140, year = {2024}, author = {Karaśkiewicz, J and Wójcik, R}, title = {Modelling optimal water retention in hydrogenic habitats using LIDAR laser data.}, journal = {The Science of the total environment}, volume = {912}, number = {}, pages = {168983}, doi = {10.1016/j.scitotenv.2023.168983}, pmid = {38036140}, issn = {1879-1026}, abstract = {Degradation of hydrogenic habitats in climate change increased rapidly. It is important that we take actions to stop this process. Solution is to increase efficiency of water usage by ecosystems - especially water based ones. Building devices for delaying surface water runoff - like locks and dams - should improve hydrogenic habitats conditions and allow surrounding ecosystems use rainwater more efficient. Modelling of small retention in forests is an important aspect in decision making schema. Aim of this paper is to point optimal solutions for height and placement of devices which delay surface water runoff to set necessary water table level for renaturalization and maintenance of degrading natural habitats. Data used for analyses were acquired in the Polanów Forest Inspectorate in West Pomeranian voivodeship because of the topography diversification and the drainage infrastructure presence. There were three research plots selected based on decreased stability of habitats and historic data stated that there were natural water reservoirs, which were drained in past. Based on 2012 LiDAR (Light Detection and Ranging) point cloud the digital terrain model (DTM) was built. Water outflow points - melioration canals - were identified and analysed for optimal device localization. In following part of research specific data for each hydrogenic habitat were used to model height of devices which delay surface water runoff. Optimal level of device and area covered by water were set for each site separately. The results were handed over to the investor for implementation, then the compliance of the assumptions of the simulation of raising the water table with the as-built field measurements was checked. Study shows that it is possible to use laser technology to optimize location and height of devices which delay surface water runoff what allows to restore degraded hydrogenic habitats. Presented method supports small local retention what increases limited water resources in this region, decreases rapid runoff of surface water which causes frequent floods. Proposed method of modelling the location and height of the dams or locks is universal. Even though results are unique for each object the method is possible to be applied to every other situation.}, } @article {pmid38036035, year = {2024}, author = {Wang, X and Zhu, Z and Sun, J and Jia, L and Cai, L and Chen, Q and Yang, W and Wang, Y and Zhang, Y and Guo, S and Liu, W and Yang, Z and Zhao, P and Wang, Z and Lv, H}, title = {Changes in iron load in specific brain areas lead to neurodegenerative diseases of the central nervous system.}, journal = {Progress in neuro-psychopharmacology & biological psychiatry}, volume = {129}, number = {}, pages = {110903}, doi = {10.1016/j.pnpbp.2023.110903}, pmid = {38036035}, issn = {1878-4216}, mesh = {Humans ; *Neurodegenerative Diseases/diagnostic imaging/pathology ; Iron ; Genome-Wide Association Study ; Magnetic Resonance Imaging/methods ; Brain/diagnostic imaging/pathology ; *Alzheimer Disease/pathology ; *Parkinson Disease ; *Multiple Sclerosis ; }, abstract = {The causes of neurodegenerative diseases remain largely elusive, increasing their personal and societal impacts. To reveal the causal effects of iron load on Parkinson's disease (PD), Alzheimer's disease (AD), amyotrophic lateral sclerosis and multiple sclerosis, we used Mendelian randomisation and brain imaging data from a UK Biobank genome-wide association study of 39,691 brain imaging samples (predominantly of European origin). Using susceptibility-weighted images, which reflect iron load, we analysed genetically significant brain regions. Inverse variance weighting was used as the main estimate, while MR Egger and weighted median were used to detect heterogeneity and pleiotropy. Nine clear associations were obtained. For AD and PD, an increased iron load was causative: the right pallidum for AD and the right caudate, left caudate and right accumbens for PD. However, a reduced iron load was identified in the right and left caudate for multiple sclerosis, the bilateral hippocampus for mixed vascular dementia and the left thalamus and bilateral accumbens for subcortical vascular dementia. Thus, changes in iron load in different brain regions have causal effects on neurodegenerative diseases. Our results are crucial for understanding the pathogenesis and investigating the treatment of these diseases.}, } @article {pmid38035964, year = {2024}, author = {Khan, S and Upadhyay, S and Dave, U and Kumar, A and Gomes, J}, title = {Structural and mechanistic insights into ALS patient derived mutations in D-amino acid oxidase.}, journal = {International journal of biological macromolecules}, volume = {256}, number = {Pt 2}, pages = {128403}, doi = {10.1016/j.ijbiomac.2023.128403}, pmid = {38035964}, issn = {1879-0003}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics ; Kinetics ; Mutation ; Serine/genetics ; }, abstract = {The D-amino acid oxidase protein modulates neurotransmission by controlling the levels of D-serine, a co-agonist of N-methyl-D-aspartate receptors. Mutations in the DAO gene have been associated with ALS, with some studies reporting pathogenic mechanisms of the R199W mutation. We have characterized two novel mutations R38H and Q201R found in ALS patients and report certain novel findings related to the R199W mutation. We report the first instance of crystal structure analysis of a patient-derived mutant of DAO, R38H, solved at 2.10 Å. The structure revealed significant perturbations and altered binding with the cofactor (FAD) and the inhibitor benzoate, supported by biochemical assays. Q201R-DAO also exhibited significantly lower ligand binding efficiency. Furthermore, kinetic analysis across all variants revealed reduced oxidase activity and substrate binding. Notably, R38H-DAO exhibited near-WT activity only at high substrate concentrations, while R199W-DAO and Q201R-DAO displayed drastic activity reduction. Additionally, structural perturbations were inferred for R199W-DAO and Q201R-DAO, evident by the higher oligomeric state in the holoenzyme form. We also observed thermal instability in case of R199W-DAO mutant. We hypothesize that the mutant enzymes may be rendered non-functional in a cellular context, potentially leading to NMDAR-associated excitotoxicity. The study provides novel insights into structural and functional aspects of DAO mutations in ALS.}, } @article {pmid38033869, year = {2023}, author = {Vukolova, MN and Yen, LY and Khmyz, MI and Sobolevsky, AI and Yelshanskaya, MV}, title = {Parkinson's disease, epilepsy, and amyotrophic lateral sclerosis-emerging role of AMPA and kainate subtypes of ionotropic glutamate receptors.}, journal = {Frontiers in cell and developmental biology}, volume = {11}, number = {}, pages = {1252953}, pmid = {38033869}, issn = {2296-634X}, support = {R37 NS083660/NS/NINDS NIH HHS/United States ; R01 NS107253/NS/NINDS NIH HHS/United States ; R01 NS083660/NS/NINDS NIH HHS/United States ; R01 AR078814/AR/NIAMS NIH HHS/United States ; R01 CA206573/CA/NCI NIH HHS/United States ; }, abstract = {Ionotropic glutamate receptors (iGluRs) mediate the majority of excitatory neurotransmission and are implicated in various neurological disorders. In this review, we discuss the role of the two fastest iGluRs subtypes, namely, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and kainate receptors, in the pathogenesis and treatment of Parkinson's disease, epilepsy, and amyotrophic lateral sclerosis. Although both AMPA and kainate receptors represent promising therapeutic targets for the treatment of these diseases, many of their antagonists show adverse side effects. Further studies of factors affecting the selective subunit expression and trafficking of AMPA and kainate receptors, and a reasonable approach to their regulation by the recently identified novel compounds remain promising directions for pharmacological research.}, } @article {pmid38033614, year = {2023}, author = {Nakken, O and Vaage, AM and Stigum, H and Heldal, E and Meyer, HE and Holmøy, T}, title = {Tuberculin responses after BCG vaccination predict amyotrophic lateral sclerosis risk.}, journal = {Brain, behavior, & immunity - health}, volume = {34}, number = {}, pages = {100704}, pmid = {38033614}, issn = {2666-3546}, abstract = {BACKGROUND: T cell infiltration around dying motor neurons is a hallmark of amyotrophic lateral sclerosis (ALS). It is not known if this immune response represents a cause or a consequence of the disease. We aimed to establish whether individual variation in regulation of a T cell driven immune response is associated with long-term ALS risk.

METHODS: Tuberculin skin test (TST) following BCG vaccination represents a standardized measure of a secondary T cell driven immune response. During a Norwegian tuberculosis screening program (1963-1975) Norwegian citizens born from 1910 to 1955 underwent TST. In those previously BCG vaccinated (median 7 years prior to TST), we related tuberculin skin tests to later ALS disease identified through validated Norwegian health registers. We fitted Cox proportional hazard models to investigate the association between tuberculin reactivity and ALS risk.

RESULTS: Among 324,629 participants (52 % women) with median age 22 (IQR 10) years at tuberculosis screening, 496 (50 % women) later developed ALS. Hazard ratio for ALS was 0.74 (95% CI 0.57-0.95) for those who remained TST negative compared to those who mounted a positive TST. The association was strongest when time between BCG immunization and TST was short. The associations observed persisted for more than four decades after TST measurement.

CONCLUSIONS: Negative TST responses after BCG vaccination is associated with decreased long-term risk for ALS development, supporting a primary role for adaptive immunity in ALS development.}, } @article {pmid38031465, year = {2024}, author = {Ghasemi, A and Sadedel, M and Moghaddam, MM}, title = {A wearable system to assist impaired-neck patients: Design and evaluation.}, journal = {Proceedings of the Institution of Mechanical Engineers. Part H, Journal of engineering in medicine}, volume = {238}, number = {1}, pages = {63-77}, doi = {10.1177/09544119231211362}, pmid = {38031465}, issn = {2041-3033}, mesh = {Humans ; *Robotics ; Electromyography/methods ; *Stroke ; Movement ; *Wearable Electronic Devices ; }, abstract = {Patients with neurological disorders, such as amyotrophic lateral sclerosis, Parkinson's disease, and cerebral palsy, often face challenges due to head-neck immobility. The conventional treatment approach involves using a neck collar to maintain an upright head position, but this can be cumbersome and restricts head-neck movements over prolonged periods. This study introduces a wearable robot capable of providing three anatomical head motions for training and assistance. The primary contributions of this research include the design of an optimized structure and the incorporation of human-robot interaction. Based on human head motion data, our primary focus centered on developing a robot capable of accommodating a significant range of neutral head movements. To ensure safety, impedance control was employed to facilitate human-robot interaction. A human study was conducted involving 10 healthy subjects who participated in an experiment to assess the robot's assistance capabilities. Passive and active modes were used to evaluate the robot's effectiveness, taking into account head-neck movement error and muscle activity levels. Surface electromyography signals (sEMG) were collected from the splenius capitis muscles during the experiment. The results demonstrated that the robot covered nearly 85% of the overall range of head rotations. Importantly, using the robot during rehabilitation led to reduced muscle activation, highlighting its potential for assisting individuals with post-stroke movement impairments.}, } @article {pmid38030693, year = {2023}, author = {Vanbilsen, N and Kotz, SA and Rosso, M and Leman, M and Triccas, LT and Feys, P and Moumdjian, L}, title = {Auditory attention measured by EEG in neurological populations: systematic review of literature and meta-analysis.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {21064}, pmid = {38030693}, issn = {2045-2322}, support = {G082021N//Fonds Wetenschappelijk Onderzoek/ ; 1295923N//Fonds Wetenschappelijk Onderzoek/ ; }, mesh = {Humans ; Cross-Sectional Studies ; *Attention ; *Parkinson Disease ; Gait ; Electroencephalography ; }, abstract = {Sensorimotor synchronization strategies have been frequently used for gait rehabilitation in different neurological populations. Despite these positive effects on gait, attentional processes required to dynamically attend to the auditory stimuli needs elaboration. Here, we investigate auditory attention in neurological populations compared to healthy controls quantified by EEG recordings. Literature was systematically searched in databases PubMed and Web of Science. Inclusion criteria were investigation of auditory attention quantified by EEG recordings in neurological populations in cross-sectional studies. In total, 35 studies were included, including participants with Parkinson's disease (PD), stroke, Traumatic Brain Injury (TBI), Multiple Sclerosis (MS), Amyotrophic Lateral Sclerosis (ALS). A meta-analysis was performed on P3 amplitude and latency separately to look at the differences between neurological populations and healthy controls in terms of P3 amplitude and latency. Overall, neurological populations showed impairments in auditory processing in terms of magnitude and delay compared to healthy controls. Consideration of individual auditory processes and thereafter selecting and/or designing the auditory structure during sensorimotor synchronization paradigms in neurological physical rehabilitation is recommended.}, } @article {pmid38030509, year = {2024}, author = {Jacobs, MT and San Gil, R and Walker, AK}, title = {UndERACting ion channels in neurodegeneration.}, journal = {Trends in neurosciences}, volume = {47}, number = {2}, pages = {87-89}, doi = {10.1016/j.tins.2023.11.002}, pmid = {38030509}, issn = {1878-108X}, mesh = {Humans ; Mice ; Animals ; *Amyotrophic Lateral Sclerosis/genetics/metabolism ; Endoplasmic Reticulum ; Ion Channels/genetics/metabolism ; Chloride Channels/metabolism ; }, abstract = {In a recent study, Guo and colleagues characterised the function of an elusive endoplasmic reticulum (ER) anion channel protein, Chloride Channel CLiC Like 1 (CLCC1), and identified rare CLCC1 variants in people with amyotrophic lateral sclerosis (ALS). CLCC1 mutants disrupted ER function in vitro and promoted ALS-like pathology and neurodegeneration in mice. This work reveals a previously uncharacterised pathway involved in ER calcium release and highlights new pathogenic mechanisms underlying neurodegeneration.}, } @article {pmid38029395, year = {2024}, author = {Song, J}, title = {Molecular Mechanisms of Phase Separation and Amyloidosis of ALS/FTD-linked FUS and TDP-43.}, journal = {Aging and disease}, volume = {15}, number = {5}, pages = {2084-2112}, pmid = {38029395}, issn = {2152-5250}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism/genetics/pathology ; *RNA-Binding Protein FUS/metabolism/chemistry/genetics ; *DNA-Binding Proteins/metabolism/chemistry/genetics ; *Frontotemporal Dementia/genetics/metabolism/pathology ; Amyloidosis/metabolism/pathology/genetics ; Phase Separation ; }, abstract = {FUS and TDP-43, two RNA-binding proteins from the heterogeneous nuclear ribonucleoprotein family, have gained significant attention in the field of neurodegenerative diseases due to their association with amyotrophic lateral sclerosis (ALS) and frontotemporal degeneration (FTD). They possess folded domains for binding ATP and various nucleic acids including DNA and RNA, as well as substantial intrinsically disordered regions (IDRs) including prion-like domains (PLDs) and RG-/RGG-rich regions. They play vital roles in various cellular processes, including transcription, splicing, microRNA maturation, RNA stability and transport and DNA repair. In particular, they are key components for forming ribonucleoprotein granules and stress granules (SGs) through homotypic or heterotypic liquid-liquid phase separation (LLPS). Strikingly, liquid-like droplets formed by FUS and TDP-43 may undergo aging to transform into less dynamic assemblies such as hydrogels, inclusions, and amyloid fibrils, which are the pathological hallmarks of ALS and FTD. This review aims to synthesize and consolidate the biophysical knowledge of the sequences, structures, stability, dynamics, and inter-domain interactions of FUS and TDP-43 domains, so as to shed light on the molecular mechanisms underlying their liquid-liquid phase separation (LLPS) and amyloidosis. The review further delves into the mechanisms through which ALS-causing mutants of the well-folded hPFN1 disrupt the dynamics of LLPS of FUS prion-like domain, providing key insights into a potential mechanism for misfolding/aggregation-prone proteins to cause neurodegenerative diseases and aging by gain of functions. With better understanding of different biophysical aspects of FUS and TDP-43, the ultimate goal is to develop drugs targeting LLPS and amyloidosis, which could mediate protein homeostasis within cells and lead to new treatments for currently intractable diseases, particularly neurodegenerative diseases such as ALS, FTD and aging. However, the study of membrane-less organelles and condensates is still in its infancy and therefore the review also highlights key questions that require future investigation.}, } @article {pmid38028604, year = {2023}, author = {Kumar, R and Madhavan, T and Ponnusamy, K and Sohn, H and Haider, S}, title = {Computational study of the motor neuron protein KIF5A to identify nsSNPs, bioactive compounds, and its key regulators.}, journal = {Frontiers in genetics}, volume = {14}, number = {}, pages = {1282234}, pmid = {38028604}, issn = {1664-8021}, abstract = {Introduction: Kinesin family member 5A (KIF5A) is a motor neuron protein expressed in neurons and involved in anterograde transportation of organelles, proteins, and RNA. Variations in the KIF5A gene that interfere with axonal transport have emerged as a distinguishing feature in several neurodegenerative disorders, including hereditary spastic paraplegia (HSP10), Charcot-Marie-Tooth disease type 2 (CMT2), and Amyotrophic Lateral Sclerosis (ALS). Methods: In this study, we implemented a computational structural and systems biology approach to uncover the role of KIF5A in ALS. Using the computational structural biology method, we explored the role of non-synonymous Single Nucleotide Polymorphism (nsSNPs) in KIF5A. Further, to identify the potential inhibitory molecule against the highly destabilizing structure variant, we docked 24 plant-derived phytochemicals involved in ALS. Results: We found KIF5A[S291F] variant showed the most structure destabilizing behavior and the phytocompound "epigallocatechin gallate" showed the highest binding affinity (-9.0 Kcal/mol) as compared to wild KIF5A (-8.4 Kcal/mol). Further, with the systems biology approach, we constructed the KIF5A protein-protein interaction (PPI) network to identify the associated Kinesin Families (KIFs) proteins, modules, and their function. We also constructed a transcriptional and post-transcriptional regulatory network of KIF5A. With the network topological parameters of PPIN (Degree, Bottleneck, Closeness, and MNC) using CytoHubba and computational knock-out experiment using Network Analyzer, we found KIF1A, 5B, and 5C were the significant proteins. The functional modules were highly enriched with microtubule motor activity, chemical synaptic transmission in neurons, GTP binding, and GABA receptor activity. In regulatory network analysis, we found KIF5A post-transcriptionally down-regulated by miR-107 which is further transcriptionally up-regulated by four TFs (HIF1A, PPARA, SREBF1, and TP53) and down-regulated by three TFs (ZEB1, ZEB2, and LIN28A). Discussion: We concluded our study by finding a crucial variant of KIF5A and its potential therapeutic target (epigallocatechin gallate) and KIF5A associated significant genes with important regulators which could decrypt the novel therapeutics in ALS and other neurodegenerative diseases.}, } @article {pmid38026702, year = {2023}, author = {Pisciottani, A and Croci, L and Lauria, F and Marullo, C and Savino, E and Ambrosi, A and Podini, P and Marchioretto, M and Casoni, F and Cremona, O and Taverna, S and Quattrini, A and Cioni, JM and Viero, G and Codazzi, F and Consalez, GG}, title = {Neuronal models of TDP-43 proteinopathy display reduced axonal translation, increased oxidative stress, and defective exocytosis.}, journal = {Frontiers in cellular neuroscience}, volume = {17}, number = {}, pages = {1253543}, pmid = {38026702}, issn = {1662-5102}, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive, lethal neurodegenerative disease mostly affecting people around 50-60 years of age. TDP-43, an RNA-binding protein involved in pre-mRNA splicing and controlling mRNA stability and translation, forms neuronal cytoplasmic inclusions in an overwhelming majority of ALS patients, a phenomenon referred to as TDP-43 proteinopathy. These cytoplasmic aggregates disrupt mRNA transport and localization. The axon, like dendrites, is a site of mRNA translation, permitting the local synthesis of selected proteins. This is especially relevant in upper and lower motor neurons, whose axon spans long distances, likely accentuating their susceptibility to ALS-related noxae. In this work we have generated and characterized two cellular models, consisting of virtually pure populations of primary mouse cortical neurons expressing a human TDP-43 fusion protein, wt or carrying an ALS mutation. Both forms facilitate cytoplasmic aggregate formation, unlike the corresponding native proteins, giving rise to bona fide primary culture models of TDP-43 proteinopathy. Neurons expressing TDP-43 fusion proteins exhibit a global impairment in axonal protein synthesis, an increase in oxidative stress, and defects in presynaptic function and electrical activity. These changes correlate with deregulation of axonal levels of polysome-engaged mRNAs playing relevant roles in the same processes. Our data support the emerging notion that deregulation of mRNA metabolism and of axonal mRNA transport may trigger the dying-back neuropathy that initiates motor neuron degeneration in ALS.}, } @article {pmid38026695, year = {2023}, author = {Donison, N and Hintermayer, M and Subramaniam, M and Santandrea, E and Volkening, K and Strong, MJ}, title = {Upregulation of LRRK2 following traumatic brain injury does not directly phosphorylate Thr[175] tau.}, journal = {Frontiers in cellular neuroscience}, volume = {17}, number = {}, pages = {1272899}, pmid = {38026695}, issn = {1662-5102}, abstract = {Phosphorylated microtubule-associated protein tau (tau) aggregates are a pathological hallmark of various neurodegenerative diseases, including chronic traumatic encephalopathy and amyotrophic lateral sclerosis with cognitive impairment. While there are many residues phosphorylated on tau, phosphorylation of threonine 175 (pThr[175] tau) has been shown to initiate fibril formation in vitro and is present in pathological tau aggregates in vivo. Given this, preventing Thr[175] tau phosphorylation presents a potential approach to reduce fibril formation; however, the kinase(s) acting on Thr[175] are not yet fully defined. Using a single controlled cortical impact rodent model of traumatic brain injury (TBI), which rapidly induces Thr[175] tau phosphorylation, we observed an upregulation and alteration in subcellular localization of leucine-rich repeat kinase 2 (LRRK2), a kinase that has been implicated in tau phosphorylation. LRRK2 upregulation was evident by one-day post-injury and persisted to day 10. The most notable changes were observed in microglia at the site of injury in the cortex. To determine if the appearance of pThr[175] tau was causally related to the upregulation of LRRK2 expression, we examined the ability of LRRK2 to phosphorylate Thr[175]in vitro by co-transfecting 2N4R human WT-tau with either LRRK2-WT, constitutively-active LRRK2-G2019S or inactive LRRK2-3XKD. We found no significant difference in the level of pThr[175] tau between the overexpression of LRRK2-WT, -G2019S or -3XKD, suggesting LRRK2 does not phosphorylate tau at Thr[175]. Further, downstream events known to follow Thr[175] phosphorylation and known to be associated with pathological tau fibril formation (pSer[9]-GSK3β and pThr[231] tau induction) also remained unchanged. We conclude that while LRRK2 expression is altered in TBI, it does not contribute directly to pThr[175] tau generation.}, } @article {pmid38025370, year = {2023}, author = {Narayan, MS and Sameer, M and Viburajah, V}, title = {Hip Fracture in a Patient with Overlap Syndrome - Conundrums Involved in the Management - A Case Report.}, journal = {Journal of orthopaedic case reports}, volume = {13}, number = {11}, pages = {106-111}, pmid = {38025370}, issn = {2250-0685}, abstract = {INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative condition producing symptoms of varying severity depending on the extent and progression of the disease pathology most importantly respiratory insufficiency and pulmonary complications. Myasthenia gravis (MG) on the other hand is an autoimmune condition due to the pathology involving failure of neuromuscular transmission causing muscle weakness exacerbated by activity and involvement of the respiratory muscles leading to respiratory failure. Overlap syndrome is a condition wherein both motor neuron disease (MND) and MG are present in the same patient. The safety of using muscle-relaxing agents in patients with MG undergoing major surgical procedures has so far been assessed as insufficient. There have been many concerns regarding anesthetic management in relation to complications with respiratory function in patients with ALS, with regional anesthesia being considered slightly safer.

CASE REPORT: An 81-year-old female presented with a closed injury to her left hip, and she was diagnosed to have a left neck of femur fracture. She was also a known case of bulbar MND with an overlap syndrome of MG. She was hypertensive and controlled with regular medication. She was planned for a left hip bipolar arthroplasty. Anesthetic requirements and management of these patients require a high degree of expertise and anesthesia in patients undergoing surgery is prone to more complications and mortality. In addition, as the patient had an overlap of both MG and MND, more meticulous assessment and management strategies were necessary.

CONCLUSION: The importance and purpose of this study are to highlight a case of overlap syndrome of MND and MG patients who sustained a left neck femur fracture and underwent bipolar arthroplasty highlighting the anesthetic considerations in the patient for the procedure. We concluded that the choice of mode of anesthesia needs to be individualized based on each patient's requirements after careful analysis of the risk-benefit ratio of general versus regional. Regional anesthesia was successfully administered for this patient.}, } @article {pmid38025276, year = {2023}, author = {Audrain, M and Egesipe, AL and Tentillier, N and Font, L and Ratnam, M and Mottier, L and Clavel, M and Le Roux-Bourdieu, M and Fenyi, A and Ollier, R and Chevalier, E and Guilhot, F and Fuchs, A and Piorkowska, K and Carlyle, B and Arnold, SE and Berry, JD and Luthi-Carter, R and Adolfsson, O and Pfeifer, A and Kosco-Vilbois, M and Seredenina, T and Afroz, T}, title = {Targeting amyotrophic lateral sclerosis by neutralizing seeding-competent TDP-43 in CSF.}, journal = {Brain communications}, volume = {5}, number = {6}, pages = {fcad306}, pmid = {38025276}, issn = {2632-1297}, abstract = {In amyotrophic lateral sclerosis, a disease driven by abnormal transactive response DNA-binding protein of 43 kDa aggregation, CSF may contain pathological species of transactive response DNA-binding protein of 43 kDa contributing to the propagation of pathology and neuronal toxicity. These species, released in part by degenerating neurons, would act as a template for the aggregation of physiological protein contributing to the spread of pathology in the brain and spinal cord. In this study, a robust seed amplification assay was established to assess the presence of seeding-competent transactive response DNA-binding protein of 43 kDa species in CSF of apparently sporadic amyotrophic lateral sclerosis patients. These samples resulted in a significant acceleration of substrate aggregation differentiating the kinetics from healthy controls. In parallel, a second assay was developed to determine the level of target engagement that would be necessary to neutralize such species in human CSF by a therapeutic monoclonal antibody targeting transactive response DNA-binding protein of 43 kDa. For this, evaluation of the pharmacokinetic/pharmacodynamic effect for the monoclonal antibody, ACI-5891.9, in vivo and in vitro confirmed that a CSF concentration of ≍1100 ng/mL would be sufficient for sustained target saturation. Using this concentration in the seed amplification assay, ACI-5891.9 was able to neutralize the transactive response DNA-binding protein of 43 kDa pathogenic seeds derived from amyotrophic lateral sclerosis patient CSF. This translational work adds to the evidence of transmission of transactive response DNA-binding protein of 43 kDa pathology via CSF that could contribute to the non-contiguous pattern of clinical manifestations observed in amyotrophic lateral sclerosis and demonstrates the ability of a therapeutic monoclonal antibody to neutralize the toxic, extracellular seeding-competent transactive response DNA-binding protein of 43 kDa species in the CSF of apparently sporadic amyotrophic lateral sclerosis patients.}, } @article {pmid38022694, year = {2023}, author = {Maselli, F and D'Antona, S and Utichi, M and Arnaudi, M and Castiglioni, I and Porro, D and Papaleo, E and Gandellini, P and Cava, C}, title = {Computational analysis of five neurodegenerative diseases reveals shared and specific genetic loci.}, journal = {Computational and structural biotechnology journal}, volume = {21}, number = {}, pages = {5395-5407}, pmid = {38022694}, issn = {2001-0370}, abstract = {Neurodegenerative diseases (ND) are heterogeneous disorders of the central nervous system that share a chronic and selective process of neuronal cell death. A computational approach to investigate shared genetic and specific loci was applied to 5 different ND: Amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), Parkinson's disease (PD), Multiple sclerosis (MS), and Lewy body dementia (LBD). The datasets were analyzed separately, and then we compared the obtained results. For this purpose, we applied a genetic correlation analysis to genome-wide association datasets and revealed different genetic correlations with several human traits and diseases. In addition, a clumping analysis was carried out to identify SNPs genetically associated with each disease. We found 27 SNPs in AD, 6 SNPs in ALS, 10 SNPs in PD, 17 SNPs in MS, and 3 SNPs in LBD. Most of them are located in non-coding regions, with the exception of 5 SNPs on which a protein structure and stability prediction was performed to verify their impact on disease. Furthermore, an analysis of the differentially expressed miRNAs of the 5 examined pathologies was performed to reveal regulatory mechanisms that could involve genes associated with selected SNPs. In conclusion, the results obtained constitute an important step toward the discovery of diagnostic biomarkers and a better understanding of the diseases.}, } @article {pmid38022487, year = {2023}, author = {Li, X and Liu, Q and Niu, T and Jia, H and Liu, T and Xin, Z and Li, Z and Zhou, X and Li, R and Liu, Y and Dong, H}, title = {Sleep Disturbances as a Potential Risk Factor for Deterioration of Respiratory Function in Patients with Amyotrophic Lateral Sclerosis.}, journal = {Annals of Indian Academy of Neurology}, volume = {26}, number = {5}, pages = {754-760}, pmid = {38022487}, issn = {0972-2327}, abstract = {OBJECTIVES: Sleep disturbances are common in amyotrophic lateral sclerosis (ALS). However, previous studies have explored sleep quality at the cross-sectional level and the longitudinal variability characteristics are currently unknown. Our study aimed to longitudinally explore the effect of sleep quality on disease progression in patients with ALS.

METHODS: All enrolled patients with ALS were first diagnosed and completed the 6- and 12-month follow-ups. Subjective sleep disturbance was assessed using the Pittsburgh Sleep Quality Index (PSQI). Based on the PSQI score at baseline, patients with ALS were classified as poor sleepers (PSQI >5) and good sleepers (PSQI ≤5). Disease progression was assessed using the rate of disease progression, the absolute change from baseline forced vital capacity (ΔFVC) and the percentage change from baseline FVC (ΔFVC%) over the follow-up period.

RESULTS: Sixty-three patients were included in the study, 24 (38.1%) were poor sleepers and 39 were good sleepers. The percentage of patients with poor sleep quality was 38.1% at baseline, increasing to 60.3% and 74.6% at 6- and 12-month, respectively. Compared to good sleepers, ΔFVC and ΔFVC% values were greater in poor sleepers (P < 0.001 and P = 0.001, respectively). Poor sleep quality at diagnosis is associated with rapid deterioration of respiratory function during disease progression.

CONCLUSIONS: Sleep disturbances maybe a potential risk factor for deterioration of respiratory function in patients with ALS. The role of sleep disturbances in disease progression deserves attention, and early assessment and intervention may slow disease progression and improve life quality of patients with ALS.}, } @article {pmid38022476, year = {2023}, author = {Chawla, T and Goyal, V}, title = {Tofersen: Silver Lining or Hyperbole??.}, journal = {Annals of Indian Academy of Neurology}, volume = {26}, number = {5}, pages = {638-640}, pmid = {38022476}, issn = {0972-2327}, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder of anterior horn cells with a dismal prognosis. Over a century since its description, we still do not have a cure for this disorder. Edaravone, Riluzole, and combination of phenylbutyrate and taurursodiol are a handful of FDA-approved drugs that only delay the progression of the disease by a few months. Tofersen, an antisense oligonucleotide, in SOD1 related ALS, has joined the bandwagon of FDA-approved drugs for ALS recently. It is a gene therapy that has been found to lower SOD1 concentrations and neurofilament light chain concentrations in blood and CSF, a known biomarker of ALS, leading to the accelerated approval of the drug. Although it did not show any statistically significant clinical improvement. In this article, we discuss the development and approval process of the first gene-based therapy, Tofersen, for ALS.}, } @article {pmid38022431, year = {2023}, author = {Hiew, FL}, title = {Sleep and Survival in Amyotrophic Lateral Sclerosis (ALS): The Parallelism in Motor and Non-Motor Progression.}, journal = {Annals of Indian Academy of Neurology}, volume = {26}, number = {5}, pages = {628}, pmid = {38022431}, issn = {0972-2327}, } @article {pmid38022117, year = {2023}, author = {Jain, A and Madkan, S and Patil, P}, title = {The Role of Gut Microbiota in Neurodegenerative Diseases: Current Insights and Therapeutic Implications.}, journal = {Cureus}, volume = {15}, number = {10}, pages = {e47861}, pmid = {38022117}, issn = {2168-8184}, abstract = {Small microscopic entities known as microbes, having a population of hundreds of billions or perhaps even in trillions, reside in our gastrointestinal tract. A healthy immune system, digestion, and creation of vitamins and enzymes are all thanks to these microbes. However, new research has shown a hitherto unrecognized connection between the microbiota of the intestines and the genesis of neurodegenerative diseases. Neurons in the CNS gradually deteriorate in neurodegenerative illnesses like multiple sclerosis and Parkinson's disease (PD). This deterioration impairs cognitive and physical function. Amyotrophic lateral sclerosis (ALS), PD, and Alzheimer's disease (AD) are just a few examples of neurodegenerative illnesses that pose a serious threat to world health and have few effective treatments. Recent research suggests that the gut microbiota, a diverse microbial population found in the gastrointestinal system, may substantially impact the cause and development of various diseases. The discovery of altered gut microbiota composition in people with these illnesses is one of the most critical lines of evidence connecting gut microbiota dysbiosis to neurodegenerative diseases. AD patients have a distinct characteristic of having a particular microbiota profile. In addition, an excess population of a specific microbe data profile is seen as compared to a healthy individual. Similar changes in the gut microbiota composition have been noted in people with multiple sclerosis and PD. The latest study indicates the potential that dysbiosis, a condition characterized by alteration in the intestinal microbiota's makeup and functioning, may have an effect on the onset and progression of neurodegenerative diseases, including PD and multiple sclerosis. In order to emphasize any potential underlying mechanisms and examine potential treatment repercussions, the review article's goal is to summarize current knowledge about the connection between gut microbiota and neurodegenerative disorders. The review article aims to summarize current knowledge about the connection between gut microbiota and neurodegenerative disorders, highlighting potential underlying mechanisms and examining potential treatment repercussions.}, } @article {pmid38021968, year = {2023}, author = {Munoz, NR and Agwuegbo, CC and Ghorbani, A and Vincent Coralde, JM and Abdelmalik, R}, title = {Takotsubo Cardiomyopathy Induced by Stress From Amyotrophic Lateral Sclerosis and a Mechanical Fall.}, journal = {Cureus}, volume = {15}, number = {10}, pages = {e47068}, pmid = {38021968}, issn = {2168-8184}, abstract = {Named after the Japanese octopus trap, Takotsubo cardiomyopathy is an acute myocardial condition characterized by a reversible ventricular dysfunction with ballooning of the left ventricle (LV) during systole. A catecholamine surge is likely the primary mechanism responsible for myocardial damage in this condition. The association between amyotrophic lateral sclerosis (ALS) and Takotsubo cardiomyopathy has not been well established. We present a unique case of Takotsubo cardiomyopathy diagnosed in a patient with ALS who presented after a fall with shortness of breath, generalized weakness, and hypotension. She was found to have troponinemia, elevated brain natriuretic peptide, and Osborn waves without ST-segment changes noted on electrocardiography (EKG). The diagnosis of Takotsubo cardiomyopathy was confirmed via transthoracic echocardiography (TTE), which revealed reduced left ventricular ejection fraction, apical ballooning of the LV, akinesis of the ventricular apex, and hyperkinesis of the base of the heart. Coronary angiography revealed no coronary artery disease. She was managed medically and was hemodynamically stable at the time of discharge.}, } @article {pmid38020614, year = {2023}, author = {Xu, D and Chu, M and Chen, Y and Fang, Y and Wang, J and Zhang, X and Xu, F}, title = {Identification and verification of ferroptosis-related genes in the pathology of epilepsy: insights from CIBERSORT algorithm analysis.}, journal = {Frontiers in neurology}, volume = {14}, number = {}, pages = {1275606}, pmid = {38020614}, issn = {1664-2295}, abstract = {BACKGROUND: Epilepsy is a neurological disorder characterized by recurrent seizures. A mechanism of cell death regulation, known as ferroptosis, which involves iron-dependent lipid peroxidation, has been implicated in various diseases, including epilepsy.

OBJECTIVE: This study aimed to provide a comprehensive understanding of the relationship between ferroptosis and epilepsy through bioinformatics analysis. By identifying key genes, pathways, and potential therapeutic targets, we aimed to shed light on the underlying mechanisms involved in the pathogenesis of epilepsy.

MATERIALS AND METHODS: We conducted a comprehensive analysis by screening gene expression data from the Gene Expression Omnibus (GEO) database and identified the differentially expressed genes (DEGs) related to ferroptosis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to gain insights into the biological processes and pathways involved. Moreover, we constructed a protein-protein interaction (PPI) network to identify hub genes, which was further validated using the receiver operating characteristic (ROC) curve analysis. To explore the relationship between immune infiltration and genes, we employed the CIBERSORT algorithm. Furthermore, we visualized four distinct interaction networks-mRNA-miRNA, mRNA-transcription factor, mRNA-drug, and mRNA-compound-to investigate potential regulatory mechanisms.

RESULTS: In this study, we identified a total of 33 differentially expressed genes (FDEGs) associated with epilepsy and presented them using a Venn diagram. Enrichment analysis revealed significant enrichment in the pathways related to reactive oxygen species, secondary lysosomes, and ubiquitin protein ligase binding. Furthermore, GSVA enrichment analysis highlighted significant differences between epilepsy and control groups in terms of the generation of precursor metabolites and energy, chaperone complex, and antioxidant activity in Gene Ontology (GO) analysis. Furthermore, during the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, we observed differential expression in pathways associated with amyotrophic lateral sclerosis (ALS) and acute myeloid leukemia (AML) between the two groups. To identify hub genes, we constructed a protein-protein interaction (PPI) network using 30 FDEGs and utilized algorithms. This analysis led to the identification of three hub genes, namely, HIF1A, TLR4, and CASP8. The application of the CIBERSORT algorithm allowed us to explore the immune infiltration patterns between epilepsy and control groups. We found that CD4-naïve T cells, gamma delta T cells, M1 macrophages, and neutrophils exhibited higher expression in the control group than in the epilepsy group.

CONCLUSION: This study identified three FDEGs and analyzed the immune cells in epilepsy. These findings pave the way for future research and the development of innovative therapeutic strategies for epilepsy.}, } @article {pmid38020597, year = {2023}, author = {Nakamura, R and Kurihara, M and Kobashi, S and Tamaki, Y and Ogawa, N and Kitamura, A and Yamakawa, I and Bamba, S and Terashima, T and Urushitani, M}, title = {Ideal body weight-based determination of minimum oral calories beneficial to function and survival in ALS.}, journal = {Frontiers in neurology}, volume = {14}, number = {}, pages = {1286153}, pmid = {38020597}, issn = {1664-2295}, abstract = {INTRODUCTION: This study sought to identify the optimal caloric intake to improve function and survival in ALS patients by comparing oral intake per ideal body weight (IBW) and its discrepancy with total energy expenditure (TEE) using the Shimizu formula.

METHODS: A retrospective analysis of 104 ALS patients was conducted, categorizing them based on their average intake during the first week after admission using two primary intake cutoffs: 25 kcal/kgIBW and 30 kcal/kgIBW. The variance between oral intake and TEE was also evaluated using -300 kcal and 0 kcal as reference points.

RESULTS: Oral caloric intake per IBW and functional decline rate (rs = -0.35, p < 0.001), but the variance from TEE was not significantly correlated (-0.11, p = 0.27). Survival data showed that patients consuming less than 25 kcal/kgIBW had a median survival of 24 months, increasing to 38 months for those consuming between 25-30 kcal/kgIBW and 63 months for those consuming 30 kcal/kgIBW or more. Deviations from the TEE did not significantly affect survival (p = 0.36). Among patients consuming less than their TEE, those consuming less than 25 kcal/kgIBW had a shorter median survival (24 months) compared to their counterparts (46 months) (p = 0.022). Consumption of less than 25 kcal/kgBW emerged as a significant negative predictor of patient outcome, independent of factors such as age, gender or disease progression.

DISCUSSION: Intakes of 25 kcal/kgIBW or more are correlated with improved ALS outcomes, and larger, multi-regional studies are recommended for deeper insights.}, } @article {pmid38020546, year = {2023}, author = {de Brito Siqueira, ALG and Cremasco, PVV and Bahú, JO and Pioli da Silva, A and Melo de Andrade, LR and González, PGA and Crivellin, S and Cárdenas Concha, VO and Krambeck, K and Lodi, L and Severino, P and Souto, EB}, title = {Phytocannabinoids: Pharmacological effects, biomedical applications, and worldwide prospection.}, journal = {Journal of traditional and complementary medicine}, volume = {13}, number = {6}, pages = {575-587}, pmid = {38020546}, issn = {2225-4110}, abstract = {Scientific evidence exists about the association between neurological diseases (i.e., Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis (ALS), multiple sclerosis, depression, and memory loss) and oxidative damage. The increasing worldwide incidence of such diseases is attracting the attention of researchers to find palliative medications to reduce the symptoms and promote quality of life, in particular, in developing countries, e.g., South America and Africa. Among potential alternatives, extracts of Cannabis Sativa L. are suitable for people who have neurological disorders, spasticity, and pain, nausea, resulting from diseases such as cancer and arthritis. In this review, we discuss the latest developments in the use of Cannabis, its subtypes and constituents, extraction methods, and relevant pharmacological effects. Biomedical applications, marketed products, and prospects for the worldwide use of Cannabis Sativa L. extracts are also discussed, providing the bibliometric maps of scientific literature published in representative countries from South America (i.e., Brazil) and Africa (i.e., South Africa). A lack of evidence on the effectiveness and safety of Cannabis, besides the concerns about addiction and other adverse events, has led many countries to act with caution before changing Cannabis-related regulations. Recent findings are expected to increase the social acceptance of Cannabis, while new technologies seem to boost the global cannabis market because the benefits of (-)-trans-delta-9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD) use have been proven in several studies in addition to the potential to general new employment.}, } @article {pmid38020004, year = {2023}, author = {Du, W and Yan, M and Yin, C and Zhang, Z}, title = {A novel modified nano-alumina composite sol for potential application in forest firefighting.}, journal = {RSC advances}, volume = {13}, number = {48}, pages = {33820-33825}, pmid = {38020004}, issn = {2046-2069}, abstract = {Herein, modified ammonium polyphosphate wrapped nano-alumina (mAPP@Als) was first synthesized and then dispersed in traditional fire extinguishing solution (FES) to fabricate a FES-mAPP@Als composite sol. It was found that the phosphorus-silica containing units were attached onto the nano-alumina surface, and the mAPP@Als particles showed excellent dispersion level in FES with a single-domain particle size distribution range. Due to the synergistic effects of the phosphorus-nitrogen and silica-alumina flame retardant components, FES-mAPP@Als (5% concentration) coated wood exhibited improved limiting oxygen index (33.2%) and carbonization ability, and depressed heat release (41.9%) and smoke production (10.7%), as compared to the pristine wood. In addition, the FES-mAPP@Als composite sol showed enhanced fire-extinguishing and anti-reignition capacities compared to the FES. This research offers a novel composite sol fire extinguishing agent for fighting forest fires.}, } @article {pmid38019651, year = {2023}, author = {Harley, P and Kerins, C and Gatt, A and Neves, G and Riccio, F and Machado, CB and Cheesbrough, A and R'Bibo, L and Burrone, J and Lieberam, I}, title = {Aberrant axon initial segment plasticity and intrinsic excitability of ALS hiPSC motor neurons.}, journal = {Cell reports}, volume = {42}, number = {12}, pages = {113509}, doi = {10.1016/j.celrep.2023.113509}, pmid = {38019651}, issn = {2211-1247}, support = {MR/N025865/1/MRC_/Medical Research Council/United Kingdom ; MR/N026063/1/MRC_/Medical Research Council/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; }, mesh = {Humans ; *Axon Initial Segment/metabolism ; *Amyotrophic Lateral Sclerosis/metabolism ; *Induced Pluripotent Stem Cells/metabolism ; Motor Neurons/metabolism ; Action Potentials/physiology ; }, abstract = {Dysregulated neuronal excitability is a hallmark of amyotrophic lateral sclerosis (ALS). We sought to investigate how functional changes to the axon initial segment (AIS), the site of action potential generation, could impact neuronal excitability in ALS human induced pluripotent stem cell (hiPSC) motor neurons. We find that early TDP-43 and C9orf72 hiPSC motor neurons show an increase in the length of the AIS and impaired activity-dependent AIS plasticity that is linked to abnormal homeostatic regulation of neuronal activity and intrinsic hyperexcitability. In turn, these hyperactive neurons drive increased spontaneous myofiber contractions of in vitro hiPSC motor units. In contrast, late hiPSC and postmortem ALS motor neurons show AIS shortening, and hiPSC motor neurons progress to hypoexcitability. At a molecular level, aberrant expression of the AIS master scaffolding protein ankyrin-G and AIS-specific voltage-gated sodium channels mirror these dynamic changes in AIS function and excitability. Our results point toward the AIS as an important site of dysfunction in ALS motor neurons.}, } @article {pmid38019415, year = {2024}, author = {Zhu, Y and Li, M and Wang, H and Yang, F and Du, R and Pang, X and Bai, J and Huang, X}, title = {Mendelian Randomization Identifies Genetically Supported Drug Targets for Amyotrophic Lateral Sclerosis and Frontotemporal Dementia.}, journal = {Molecular neurobiology}, volume = {61}, number = {7}, pages = {3809-3818}, pmid = {38019415}, issn = {1559-1182}, mesh = {*Amyotrophic Lateral Sclerosis/genetics/drug therapy ; *Frontotemporal Dementia/genetics/drug therapy ; Humans ; *Mendelian Randomization Analysis/methods ; Genome-Wide Association Study ; Quantitative Trait Loci ; Drug Repositioning/methods ; }, abstract = {Currently, amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) have no effective treatments. Drug repurposing offers a rapid method to meet therapeutic need for ALS and FTD. To identify therapeutic targets associated with ALS and FTD, Mendelian randomization (MR) analysis and colocalization were performed. Genetic instruments were based on transcriptomic and proteomic data for 422 actionable proteins targeted by approved drugs or clinical drug candidates. The publicly available ALS GWAS summary data (including a total of 20,806 ALS cases and 59,804 controls) and FTD GWAS summary data (including a total of 2154 patients with FTD and 4308 controls) were used. Using cis-expression quantitative trait loci and cis-protein quantitative trait loci genetic instruments, we identified several drug targets for repurposing (ALS: MARK3, false-discovery rate (FDR) = 0.043; LTBR, FDR = 0.068) (FTD: HLA-DRB1, FDR = 0.083; ADH5, FDR = 0.056). Our MR study analyzed the actionable druggable proteins and provided potential therapeutic targets for ALS and FTD. Future studies should further elucidate the underlying mechanism of corresponding drug targets in the pathogenesis of ALS and FTD.}, } @article {pmid38019311, year = {2023}, author = {Rothstein, JD and Baskerville, V and Rapuri, S and Mehlhop, E and Jafar-Nejad, P and Rigo, F and Bennett, F and Mizielinska, S and Isaacs, A and Coyne, AN}, title = {G2C4 targeting antisense oligonucleotides potently mitigate TDP-43 dysfunction in human C9orf72 ALS/FTD induced pluripotent stem cell derived neurons.}, journal = {Acta neuropathologica}, volume = {147}, number = {1}, pages = {1}, pmid = {38019311}, issn = {1432-0533}, support = {R00 NS123242/NS/NINDS NIH HHS/United States ; R01 NS132836/NS/NINDS NIH HHS/United States ; }, mesh = {Humans ; Oligonucleotides, Antisense/pharmacology ; *Frontotemporal Dementia/genetics ; *Amyotrophic Lateral Sclerosis/genetics ; C9orf72 Protein/genetics ; *Induced Pluripotent Stem Cells ; DNA-Binding Proteins/genetics ; RNA, Antisense ; Dipeptides ; Neurons ; }, abstract = {The G4C2 repeat expansion in the C9orf72 gene is the most common genetic cause of Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Many studies suggest that dipeptide repeat proteins produced from this repeat are toxic, yet, the contribution of repeat RNA toxicity is under investigated and even less is known regarding the pathogenicity of antisense repeat RNA. Recently, two clinical trials targeting G4C2 (sense) repeat RNA via antisense oligonucleotide failed despite a robust decrease in sense-encoded dipeptide repeat proteins demonstrating target engagement. Here, in this brief report, we show that G2C4 antisense, but not G4C2 sense, repeat RNA is sufficient to induce TDP-43 dysfunction in induced pluripotent stem cell (iPSC) derived neurons (iPSNs). Unexpectedly, only G2C4, but not G4C2 sense strand targeting, ASOs mitigate deficits in TDP-43 function in authentic C9orf72 ALS/FTD patient iPSNs. Collectively, our data suggest that the G2C4 antisense repeat RNA may be an important therapeutic target and provide insights into a possible explanation for the recent G4C2 ASO clinical trial failure.}, } @article {pmid38018433, year = {2023}, author = {Naylor, K and Chrzanowska-Wąsik, M and Okońska, P and Kucmin, T and Al-Wathinani, AM and Goniewicz, K}, title = {Adapting to a Pandemic: Web-Based Residency Training and Script Concordance Testing in Emergency Medicine During COVID-19.}, journal = {Disaster medicine and public health preparedness}, volume = {17}, number = {}, pages = {e541}, doi = {10.1017/dmp.2023.195}, pmid = {38018433}, issn = {1938-744X}, mesh = {Humans ; Child ; *Internship and Residency ; Educational Measurement/methods ; Pandemics ; *COVID-19/epidemiology ; Education, Medical, Continuing/methods ; *Emergency Medicine/education ; Clinical Competence ; Internet ; }, abstract = {OBJECTIVE: The coronavirus disease (COVID-19) pandemic necessitated alternative methods to ensure the continuity of medical education. Our study explores the efficacy and acceptability of a digital continuous medical education initiative for medical residents during this challenging period.

METHODS: From September to December 2020, 47 out of 60 enrolled trainee doctors participated in this innovative digital Continuous Medical Education (CME) approach. We utilized the Script Concordance Test to bolster clinical reasoning skills. Three simulation scenarios, namely Advanced Trauma Life Support (ATLS), Advanced Life Support (ALS), and European Paediatric Life Support (EPLS), were transformed into interactive online sessions via Zoom™. Participant feedback was also collected through a survey.

RESULTS: Consistent Script Concordance Testing (SCT) scores among participants indicated the effectiveness of the online training module. Feedback suggested a broad acceptance of this novel training approach. However, discrepancies observed between formative SCT scores, and summative Multiple-Choice Questions (MCQ) assessments highlighted areas for potential refinement.

CONCLUSIONS: Our findings showcase the resilience and adaptability of medical education amidst challenges like the global pandemic. The success of methodologies such as SCT, endorsed by prestigious bodies like the European Resuscitation Council and the American Heart Association, suggests their potential in preparing health care professionals for emergent situations. This research offers valuable insights for shaping future online CME strategies.}, } @article {pmid38018200, year = {2024}, author = {Monteiro, KLC and de Aquino, TM and da Silva-Júnior, EF}, title = {Natural Compounds as Inhibitors of Aβ Peptide and Tau Aggregation.}, journal = {CNS & neurological disorders drug targets}, volume = {23}, number = {10}, pages = {1234-1250}, pmid = {38018200}, issn = {1996-3181}, mesh = {Humans ; *tau Proteins/metabolism/antagonists & inhibitors ; *Amyloid beta-Peptides/metabolism/antagonists & inhibitors ; *Biological Products/pharmacology/therapeutic use ; *Alzheimer Disease/drug therapy/metabolism ; Animals ; Plaque, Amyloid/drug therapy/metabolism ; Protein Aggregation, Pathological/drug therapy ; Neurofibrillary Tangles/drug effects/metabolism ; }, abstract = {Neurodegenerative conditions like Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS) encompass disorders characterized by the degeneration of neurons in specific circumstances. The quest for novel agents to influence these diseases, particularly AD, has unearthed various natural compounds displaying multifaceted activities and diverse pharmacological mechanisms. Given the ongoing extensive study of pathways associated with the accumulation of neurofibrillary aggregates and amyloid plaques, this paper aims to comprehensively review around 130 studies exploring natural products. These studies focus on inhibiting the formation of amyloid plaques and tau protein tangles, with the objective of potentially alleviating or delaying AD.}, } @article {pmid38018119, year = {2024}, author = {Brown, A and Armon, C and Barkhaus, P and Beauchamp, M and Bertorini, T and Bromberg, M and Cadavid, JM and Carter, GT and Crayle, J and Feldman, EL and Heiman-Patterson, T and Jhooty, S and Linares, A and Li, X and Mallon, E and Mcdermott, C and Mushannen, T and Nathaniel, G and Pattee, G and Pierce, K and Ratner, D and Slactova, L and Wicks, P and Bedlack, R}, title = {ALSUntangled #72: Insulin.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {25}, number = {3-4}, pages = {416-419}, doi = {10.1080/21678421.2023.2288110}, pmid = {38018119}, issn = {2167-9223}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy ; Insulin/adverse effects ; }, abstract = {ALSUntangled reviews alternative and off-label treatments for people living with amyotrophic lateral sclerosis (PALS). Here we review insulin, which has at least one plausible mechanism for slowing ALS progression. However, pre-clinical studies are limited and there have been no trials in PALS yet. Insulin use in patients without a metabolic need may cause very serious and potentially lethal side effects. While further studies to evaluate potential benefits may be warranted, at this time we cannot endorse insulin treatment to slow ALS progression.}, } @article {pmid38017952, year = {2023}, author = {Li, Y and Chen, M and Qi, J and Deng, C and Du, L and Bo, Z and Han, C and Mao, Z and He, Y and Shao, X and Han, S}, title = {Underwater ghost imaging with detection distance up to 9.3 attenuation lengths.}, journal = {Optics express}, volume = {31}, number = {23}, pages = {38457-38474}, doi = {10.1364/OE.499186}, pmid = {38017952}, issn = {1094-4087}, abstract = {Underwater ghost imaging LiDAR is an effective method of underwater detection. In this research, theoretical and experimental investigations were conducted on underwater ghost imaging, combining the underwater optical field transmission model with the inherent optical parameters of a water body. In addition, the Wells model and the approximate Sahu-Shanmugam scattering phase function were used to create a model for underwater optical transmission. The second-order Glauber function of the optical field was then employed to analyze the scattering field degradation during the transmission process. The simulation and experimental results verified that the proposed underwater model could better reveal the degrading effect of a water body on ghost imaging. A further series of experiments comparing underwater ghost imaging at different detection distances was also conducted. In the experimental system, gated photomultiplier tube (PMT) was used to filter out the peak of backscattering, allowing a larger gain to be set for longer-range detection of the target. The laser with a central wavelength of 532 nm was operated at a frequency of 2 KHz, with a single pulse energy of 2 mJ, a pulse width of 10 ns. High-reflective targets were imaged up to 65.2 m (9.3 attenuation lengths (ALs), attenuation coefficient c = 0.1426 m[-1], and scattering coefficient b = 0.052 m[-1]) and diffuse-reflection targets up to 41.2 m (6.4 ALs, c = 0.1569 m[-1], and b = 0.081 m[-1]). For the Jerlov-I (c = 0.048 m[-1] and b = 0.002 m[-1]) water body, the experimentally obtained maximum detection distance of 9.3 ALs can be equivalent to 193.7 m under the same optical system conditions.}, } @article {pmid38015828, year = {2023}, author = {Iyer, AK and Schoch, KM and Verbeck, A and Galasso, G and Chen, H and Smith, S and Oldenborg, A and Miller, TM and Karch, CM and Bonni, A}, title = {Targeted ASO-mediated Atp1a2 knockdown in astrocytes reduces SOD1 aggregation and accelerates disease onset in mutant SOD1 mice.}, journal = {PloS one}, volume = {18}, number = {11}, pages = {e0294731}, pmid = {38015828}, issn = {1932-6203}, support = {R01 NS078398/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Mice ; *Amyotrophic Lateral Sclerosis/pathology ; Astrocytes/metabolism ; Disease Models, Animal ; Mice, Transgenic ; Motor Neurons/metabolism ; Sodium-Potassium-Exchanging ATPase/metabolism ; Spinal Cord/metabolism ; Superoxide Dismutase/metabolism ; Superoxide Dismutase-1/genetics/metabolism ; }, abstract = {Astrocyte-specific ion pump α2-Na+/K+-ATPase plays a critical role in the pathogenesis of amyotrophic lateral sclerosis (ALS). Here, we test the effect of Atp1a2 mRNA-specific antisense oligonucleotides (ASOs) to induce α2-Na+/K+-ATPase knockdown in the widely used ALS animal model, SOD1*G93A mice. Two ASOs led to efficient Atp1a2 knockdown and significantly reduced SOD1 aggregation in vivo. Although Atp1a2 ASO-treated mice displayed no off-target or systemic toxicity, the ASO-treated mice exhibited an accelerated disease onset and shorter lifespan than control mice. Transcriptomics studies reveal downregulation of genes involved in oxidative response, metabolic pathways, trans-synaptic signaling, and upregulation of genes involved in glutamate receptor signaling and complement activation, suggesting a potential role for these molecular pathways in de-coupling SOD1 aggregation from survival in Atp1a2 ASO-treated mice. Together, these results reveal a role for α2-Na+/K+-ATPase in SOD1 aggregation and highlight the critical effect of temporal modulation of genetically validated therapeutic targets in neurodegenerative diseases.}, } @article {pmid38014926, year = {2024}, author = {Giometto, S and Finocchietti, M and Paoletti, O and Lombardi, N and Celani, MG and Sciancalepore, F and Lucenteforte, E and Kirchmayer, U and , }, title = {Adherence to riluzole therapy in patients with amyotrophic lateral sclerosis in three Italian regions-The CAESAR study.}, journal = {Pharmacoepidemiology and drug safety}, volume = {33}, number = {1}, pages = {e5736}, doi = {10.1002/pds.5736}, pmid = {38014926}, issn = {1099-1557}, support = {//Agenzia Italiana del Farmaco, Ministero della Salute/ ; }, mesh = {Male ; Humans ; Aged ; Riluzole/adverse effects ; *Amyotrophic Lateral Sclerosis/drug therapy/epidemiology/chemically induced ; Retrospective Studies ; *Neurodegenerative Diseases/chemically induced/drug therapy ; *Neuroprotective Agents/therapeutic use ; Italy/epidemiology ; }, abstract = {PURPOSE: Amyotrophic lateral sclerosis (ALS) is a rare neurodegenerative disease. Riluzole may increase survival and delay the need for mechanical ventilation. The CAESAR project ('Comparative evaluation of the efficacy and safety of drugs used in rare neuromuscular and neurodegenerative diseases', FV AIFA project 2012-2013-2014) involves evaluating prescribing patterns, and analysing effectiveness and comparative safety of drugs, in patients with neurodegenerative diseases. The aim of this study is to evaluate adherence to riluzole in patients with ALS during the first year of use, identifying adherence clusters.

METHODS: A retrospective cohort study was conducted using administrative data from Latium, Tuscany, and Umbria. We identified subjects with a new diagnosis of ALS between 2014 and 2019, with the first dispensation of riluzole within 180 days of diagnosis. We considered a two-year look-back period for the characterization of patients, and we followed them from the date of first dispensing of riluzole for 1 year. We calculated 12 monthly adherence measures, through a modified version of the Medication Possession Ratio, estimating drug coverage with Defined Daily Dose. Adherence trajectories were identified using a three-step method: (1) calculation of statistical measures; (2) principal component analysis; (3) cluster analysis. Patient characteristics at baseline and during follow-up were described and compared between adherence groups identified.

RESULTS: We included 264 ALS patients as new users of riluzole in Latium, 344 in Tuscany, and 63 in Umbria. We observed a higher frequency of males (56.2%) and a mean age of 67.4 (standard deviation, SD, 10.4) in the overall population. We identified two clusters in all regions: one more numerous, including adherent patients (60%, 74%, 88%, respectively), and another one including patients who discontinued therapy (40%, 26%, 12%, respectively). In Tuscany patients discontinuing riluzole more frequently died (28.6% vs. 15.4%, p-value <0.01). Additionally, low-adherers had a higher frequency of central nervous system disorders (69.0% vs. 52.5%, p-value 0.01), and a greater use of non-pharmacological treatments (p-values ≤0.01 for invasive ventilation and tracheostomy). We did not observe any differences in Lazio, whereas in Umbria we observed a higher use of drugs for dementia-related psychiatric problems among low-adherers (57.1% vs. 7.8%, respectively, p-value <0.01), although with small numbers.

CONCLUSION: Most ALS patients who start riluzole adhere to therapy during the first year. Patients who discontinue therapy early show greater fragility and mortality.}, } @article {pmid38014869, year = {2024}, author = {Li, X and Pura, J and Allen, A and Owzar, K and Lu, J and Harms, M and Xie, J}, title = {DYNATE: Localizing rare-variant association regions via multiple testing embedded in an aggregation tree.}, journal = {Genetic epidemiology}, volume = {48}, number = {1}, pages = {42-55}, pmid = {38014869}, issn = {1098-2272}, support = {R01 HG012555/HG/NHGRI NIH HHS/United States ; 1R01HG012555-01/GF/NIH HHS/United States ; }, mesh = {Humans ; *Genetic Variation ; *Trees ; Models, Genetic ; Genetic Association Studies ; Mutation ; Genome-Wide Association Study/methods ; Autophagy-Related Proteins ; Vesicular Transport Proteins ; }, abstract = {Rare-variants (RVs) genetic association studies enable researchers to uncover the variation in phenotypic traits left unexplained by common variation. Traditional single-variant analysis lacks power; thus, researchers have developed various methods to aggregate the effects of RVs across genomic regions to study their collective impact. Some existing methods utilize a static delineation of genomic regions, often resulting in suboptimal effect aggregation, as neutral subregions within the test region will result in an attenuation of signal. Other methods use varying windows to search for signals but often result in long regions containing many neutral RVs. To pinpoint short genomic regions enriched for disease-associated RVs, we developed a novel method, DYNamic Aggregation TEsting (DYNATE). DYNATE dynamically and hierarchically aggregates smaller genomic regions into larger ones and performs multiple testing for disease associations with a controlled weighted false discovery rate. DYNATE's main advantage lies in its strong ability to identify short genomic regions highly enriched for disease-associated RVs. Extensive numerical simulations demonstrate the superior performance of DYNATE under various scenarios compared with existing methods. We applied DYNATE to an amyotrophic lateral sclerosis study and identified a new gene, EPG5, harboring possibly pathogenic mutations.}, } @article {pmid38014622, year = {2023}, author = {Yamashita, T and Nakano, Y and Sasaki, R and Tadokoro, K and Omote, Y and Yunoki, T and Kawahara, Y and Matsumoto, N and Taira, Y and Matsuoka, C and Morihara, R and Abe, K}, title = {Safety and Clinical Effects of a Muse Cell-Based Product in Patients With Amyotrophic Lateral Sclerosis: Results of a Phase 2 Clinical Trial.}, journal = {Cell transplantation}, volume = {32}, number = {}, pages = {9636897231214370}, pmid = {38014622}, issn = {1555-3892}, mesh = {Animals ; Mice ; Humans ; *Amyotrophic Lateral Sclerosis/drug therapy ; Alprostadil/therapeutic use ; Interleukin-6 ; Tumor Necrosis Factor-alpha ; Motor Neurons ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is characterized by progressive loss of motor neurons. Multilineage-differentiating stress-enduring (Muse) cells are unique endogenous stem cells that show therapeutic effects on motor function in ALS mouse models. We conducted a single-center open phase II clinical trial to evaluate the safety and clinical effects of repeated intravenous injections of an allogenic Muse cell-based product, CL2020, in patients with ALS. Five patients with ALS received CL2020 intravenously once a month for a total of six doses. The primary endpoints were safety and tolerability, and the secondary endpoint was the rate of change in the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) score. In addition, serum tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), sphingosine-1-phosphate (S1P), cerebrospinal fluid chitotriosidase-1 (CHIT-1), and neurofilament light chain (NfL) levels were evaluated. The CL2020 treatment was highly tolerated without serious side effects. The ALSFRS-R score change trended upward at 12 months post-CL2020 treatment compared with that at 3 months pre-administration, but the difference was not statistically significant. Among five patients diagnosed with ALS, three exhibited a decrease in the rate of ALSFRS-R score change, one demonstrated an increase, and another showed no change. In addition, the patients' serum IL-6 and TNF-α levels and cerebrospinal fluid CHIT-1 and NfL levels increased for up to 6 months post-treatment; however, their serum S1P levels continuously decreased over 12 months. These findings indicate a favorable safety profile of CL2020 therapy. In the near future, a double-blind study of a larger number of ALS patients should be conducted to confirm the efficacy of ALS treatment with CL2020.}, } @article {pmid38014545, year = {2023}, author = {Pestelacci, S and Hofer-Inteeworn, N and Dennler, M and Glaus, T}, title = {Balloon dilation and transient stenting of unilateral membranous choanal atresia in a British Shorthair cat with chronic purulent rhinitis and ascending meningoencephalitis.}, journal = {Schweizer Archiv fur Tierheilkunde}, volume = {165}, number = {12}, pages = {793-800}, doi = {10.17236/sat00414}, pmid = {38014545}, issn = {1664-2848}, mesh = {Humans ; Animals ; Cats ; *Rhinitis/surgery/veterinary ; *Choanal Atresia/surgery/veterinary ; Constriction, Pathologic/surgery/veterinary ; Dilatation/veterinary ; *Cat Diseases/surgery ; }, abstract = {Choanal atresia is a rare congenital anomaly in humans and animals, characterized by the absence of communication of one or both nasal cavities with the nasopharynx. The severity of clinical signs depends on the presence of unilateral versus bilateral stenosis as well as comorbidities. With bilateral atresia, respiration may be severely compromised particularly during sleep, as airflow can only occur when breathing through the open mouth. Various therapeutic modalities have been described in people and adopted for animals. All treatments may be associated with complications, the most important being post-therapeutic scar formation with re-stenosis. This report describes a 10-month-old British Shorthair cat with chronic unilateral serosal nasal discharge that changed to mucopurulent discharge. When acute neurological signs developed, the cat was presented to the veterinary hospital. A diagnosis of primary, membranous right sided choanal atresia was achieved via computed tomography (CT) and nasopharyngeal (posterior) rhinoscopy. Secondary changes included destructive rhinitis with progression to the CNS with a subdural empyema and meningoencephalitis. Retinal changes and aspiration bronchopneumonia were suspected additional complications. After recovery from the secondary infections, the membranous obstruction was perforated and dilated using a valvuloplasty balloon by an orthograde transnasal approach under endoscopic guidance from a retroflexed nasopharyngeal view. To prevent re-stenosis, a foley catheter was placed as a transient stent for 6 days. The cat recovered uneventfully and was asymptomatic after the stent removal. Endoscopic re-examination after 5 months confirmed a persistent opening and patency of the generated right choanal passage. The cat remains asymptomatic 10 months after the procedure. Transnasal endoscopic balloon dilation and transient stenting of choanal atresia is a minimally invasive and relatively simple procedure with potentially sustained success.}, } @article {pmid38014237, year = {2023}, author = {Alvarado, CX and Weller, CA and Johnson, N and Leonard, HL and Singleton, AB and Reed, X and Blauewendraat, C and Nalls, MA}, title = {Human brain single nucleus cell type enrichments in neurodegenerative diseases.}, journal = {Research square}, volume = {}, number = {}, pages = {}, pmid = {38014237}, issn = {2693-5015}, support = {Z01 AG000949/ImNIH/Intramural NIH HHS/United States ; ZIA AG000534/ImNIH/Intramural NIH HHS/United States ; ZIA NS003154/ImNIH/Intramural NIH HHS/United States ; }, abstract = {BACKGROUND: Single-cell RNA sequencing has opened a window into clarifying the complex underpinnings of disease, particularly in quantifying the relevance of tissue- and cell-type-specific gene expression.

METHODS: To identify the cell types and genes important to therapeutic target development across the neurodegenerative disease spectrum, we leveraged genome-wide association studies, recent single-cell sequencing data, and bulk expression studies in a diverse series of brain region tissues.

RESULTS: We were able to identify significant immune-related cell types in the brain across three major neurodegenerative diseases: Alzheimer's disease, amyotrophic lateral sclerosis, and Parkinson's disease. Subsequently, putative roles of 30 fine-mapped loci implicating seven genes in multiple neurodegenerative diseases and their pathogenesis were identified.

CONCLUSIONS: We have helped refine the genetic regions and cell types effected across multiple neurodegenerative diseases, helping focus future translational research efforts.}, } @article {pmid38014203, year = {2023}, author = {Wilkins, OG and Chien, MZYJ and Wlaschin, JJ and Pisliakova, M and Thompson, D and Digby, H and Simkin, RL and Diaz, JA and Mehta, PR and Keuss, MJ and Zanovello, M and Brown, AL and Harley, P and Darbey, A and Karda, R and Fisher, EMC and Cunningham, TJ and Le Pichon, CE and Ule, J and Fratta, P}, title = {Creation of de novo cryptic splicing for ALS/FTD precision medicine.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {38014203}, issn = {2692-8205}, support = {/WT_/Wellcome Trust/United Kingdom ; MR/S006508/1/MRC_/Medical Research Council/United Kingdom ; U54 NS123743/NS/NINDS NIH HHS/United States ; ZIA HD008966/ImNIH/Intramural NIH HHS/United States ; }, abstract = {A system enabling the expression of therapeutic proteins specifically in diseased cells would be transformative, providing greatly increased safety and the possibility of pre-emptive treatment. Here we describe "TDP-REG", a precision medicine approach primarily for amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), which exploits the cryptic splicing events that occur in cells with TDP-43 loss-of-function (TDP-LOF) in order to drive expression specifically in diseased cells. In addition to modifying existing cryptic exons for this purpose, we develop a deep-learning-powered algorithm for generating customisable cryptic splicing events, which can be embedded within virtually any coding sequence. By placing part of a coding sequence within a novel cryptic exon, we tightly couple protein expression to TDP-LOF. Protein expression is activated by TDP-LOF in vitro and in vivo, including TDP-LOF induced by cytoplasmic TDP-43 aggregation. In addition to generating a variety of fluorescent and luminescent reporters, we use this system to perform TDP-LOF-dependent genomic prime editing to ablate the UNC13A cryptic donor splice site. Furthermore, we design a panel of tightly gated, autoregulating vectors encoding a TDP-43/Raver1 fusion protein, which rescue key pathological cryptic splicing events. In summary, we combine deep-learning and rational design to create sophisticated splicing sensors, resulting in a platform that provides far safer therapeutics for neurodegeneration, potentially even enabling preemptive treatment of at-risk individuals.}, } @article {pmid38014069, year = {2023}, author = {Yang, S and Wijegunawardana, D and Sheth, U and Veire, AM and Salgado, JMS and Agrawal, M and Zhou, J and Pereira, JD and Gendron, TF and Guo, JU}, title = {Aberrant splicing exonizes C9ORF72 repeat expansion in ALS/FTD.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {38014069}, issn = {2692-8205}, support = {DP2 GM132930/GM/NIGMS NIH HHS/United States ; R35 GM152208/GM/NIGMS NIH HHS/United States ; }, abstract = {A nucleotide repeat expansion (NRE) in the first annotated intron of the C9ORF72 gene is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). While C9 NRE-containing RNAs can be translated into several toxic dipeptide repeat proteins, how an intronic NRE can assess the translation machinery in the cytoplasm remains unclear. By capturing and sequencing NRE-containing RNAs from patient-derived cells, we found that C9 NRE was exonized by the usage of downstream 5' splice sites and exported from the nucleus in a variety of spliced mRNA isoforms. C9ORF72 aberrant splicing was substantially elevated in both C9 NRE[+] motor neurons and human brain tissues. Furthermore, NREs above the pathological threshold were sufficient to activate cryptic splice sites in reporter mRNAs. In summary, our results revealed a crucial and potentially widespread role of repeat-induced aberrant splicing in the biogenesis, localization, and translation of NRE-containing RNAs.}, } @article {pmid38013452, year = {2024}, author = {Smith, EN and Lee, J and Prilutsky, D and Zicha, S and Wang, Z and Han, S and Zach, N}, title = {Plasma neurofilament light levels show elevation two years prior to diagnosis of amyotrophic lateral sclerosis in the UK Biobank.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {25}, number = {1-2}, pages = {170-176}, doi = {10.1080/21678421.2023.2285428}, pmid = {38013452}, issn = {2167-9223}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/genetics ; Cohort Studies ; Biomarkers ; Biological Specimen Banks ; Intermediate Filaments ; *Neurodegenerative Diseases ; UK Biobank ; Neurofilament Proteins ; }, abstract = {OBJECTIVE: Amyotrophic lateral sclerosis (ALS) is a debilitating neurodegenerative disease with profound unmet need. In patients carrying genetic mutations, elevations in neurofilament light (NfL) have been shown to precede symptom onset, however, the natural history of NfL in general ALS patients is less characterized.

METHODS: We performed a secondary analysis of the UK Biobank Pharma Proteomics Project (UKB-PPP), a subset of the UK Biobank, a population-based cohort study in the United Kingdom, to examine plasma NfL levels in 237 participants subsequently diagnosed with ALS. We applied logistic and Cox proportional hazards regression to compare cases to 42,752 population-based and 948 age and sex-matched controls. Genetic information was obtained from exome and genotype array data.Results and Conclusions: We observed that NfL was 1.42-fold higher in cases vs population-based controls. At two to three years pre-diagnosis, NfL levels in patients exceeded the 95[th] percentile of age and sex-matched controls. A time-to-diagnosis analysis showed that a 2-fold increase in NfL levels was associated with a 3.4-fold risk of diagnosis per year, with NfL being most predictive of case status at two years (AUC = 0.96). Participants with genetic variation that might put them at risk for familial disease (N = 46) did not show a different pattern of association than those without (N = 191).

DISCUSSION: Our findings show that NfL is elevated and discriminative of future ALS diagnosis up to two years prior to diagnosis in patients with and without genetic risk variants.}, } @article {pmid38013317, year = {2023}, author = {Wang, Z and Yang, H and Han, Y and Teng, J and Kong, X and Qi, X}, title = {Screening and identification of key biomarkers associated with amyotrophic lateral sclerosis and depression using bioinformatics.}, journal = {Medicine}, volume = {102}, number = {47}, pages = {e36265}, pmid = {38013317}, issn = {1536-5964}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/genetics ; Depression/diagnosis/genetics ; Gene Expression Profiling ; *MicroRNAs/genetics ; Biomarkers ; Gene Regulatory Networks ; Computational Biology/methods ; }, abstract = {This study aims to identify common molecular biomarkers between amyotrophic lateral sclerosis (ALS) and depression using bioinformatics methods, in order to provide potential targets and new ideas and methods for the diagnosis and treatment of these diseases. Microarray datasets GSE139384, GSE35978 and GSE87610 were obtained from the Gene Expression Omnibus (GEO) database, and differentially expressed genes (DEGs) between ALS and depression were identified. After screening for overlapping DEGs, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed. Furthermore, a protein-protein interaction (PPI) network was constructed using the STRING database and Cytoscape software, and hub genes were identified. Finally, a network between miRNAs and hub genes was constructed using the NetworkAnalyst tool, and possible key miRNAs were predicted. A total of 357 genes have been identified as common DEGs between ALS and depression. GO and KEGG enrichment analyses of the 357 DEGs showed that they were mainly involved in cytoplasmic translation. Further analysis of the PPI network using Cytoscape and MCODE plugins identified 6 hub genes, including mitochondrial ribosomal protein S12 (MRPS12), poly(rC) binding protein 1 (PARP1), SNRNP200, PCBP1, small G protein signaling modulator 1 (SGSM1), and DNA methyltransferase 1 (DNMT1). Five possible target miRNAs, including miR-221-5p, miR-21-5p, miR-100-5p, miR-30b-5p, and miR-615-3p, were predicted by constructing a miRNA-gene network. This study used bioinformatics techniques to explore the potential association between ALS and depression, and identified potential biomarkers. These biomarkers may provide new ideas and methods for the early diagnosis, treatment, and monitoring of ALS and depression.}, } @article {pmid38011840, year = {2024}, author = {Asawadethmetakul, P and Xie, F and Xie, C and Ma, J and You, Y and Yao, F}, title = {Effect of Tuina Combined with Chinese Herbal Compress on Primary Dysmenorrhea with Cold Coagulation and Blood Stasis Syndrome: A Study Protocol for a Randomized Controlled Trial.}, journal = {Complementary medicine research}, volume = {31}, number = {1}, pages = {20-29}, doi = {10.1159/000534335}, pmid = {38011840}, issn = {2504-2106}, mesh = {Female ; Humans ; *Dysmenorrhea/drug therapy ; China ; *Pain Threshold ; Randomized Controlled Trials as Topic ; Observational Studies as Topic ; }, abstract = {INDRODUCTION: Primary dysmenorrhea (PD) is a very common issue in young women that reduces the quality of women's lives. Both Western medicine and traditional Chinese medicine (TCM) provide several ways to treat PD; however, TCM treatment exhibits fewer side effects for the patient. Tuina massage and Chinese herbal compresses are considered forms of external TCM therapy that have been widely used to treat PD, especially in China. Therefore, to provide the most effective and safe treatment for PD, we combined Tuina and Chinese herbal compresses together in this observational study.

METHODS: A randomized controlled trial (RCT) consisting of 114 participants from the Shanghai University of Traditional Chinese Medicine who meet inclusion criteria will be divided into two groups in a 1:1 allocation ratio. The intervention group will receive Tuina combined with Chinese herbal compress therapy, while the control group will only receive Chinese herbal compress therapy. The treatment will be given 3 days before menstruation (once per day, 3 times per menstrual cycle). The primary outcome will be measured with the Visual Analog Scale (VAS). The secondary outcomes will be measured by the Dysmenorrhea Symptom Score, the Chinese Medical Dysmenorrhea Symptom Score, the Self-Rating Anxiety Scale (SAS), the Self-Rating Depression Scale (SDS), and the pain threshold at Guanyuan (CV4).

CONCLUSION: This study will be the first RCT that will entail the combination of Tuina and Chinese herbal compresses to treat PD in the category of cold coagulation and blood stasis syndrome. If the results demonstrate that Tuina combined with a Chinese herbal compress is effective, we posit that this study will provide evidence-based references for a potential alternative treatment to treat PD in the future.

UNLABELLED: EinleitungDie primäre Dysmenorrhoe (PD) ist ein Problem, das bei jungen Frauen sehr häufig auftritt und ihre Lebensqualität beeinträchtigt. Sowohl die westliche Medizin als auch die traditionelle chinesische Medizin (TCM) bieten verschiedene Therapiemöglichkeiten zur Behandlung der PD, allerdings ist die TCM mit weniger Nebenwirkungen für die Patientin verbunden. Tuina-Massage und chinesische Kräuterkompressen gelten als Formen der äußerlichen TCM-Therapie, die besonders in China zur Behandlung der PD weit verbreitet sind. Daher haben wir in dieser Beobachtungsstudie Tuina und chinesische Kräuterkompressen kombiniert, um eine möglichst wirksame und sichere Behandlung der PD bereitzustellen.MethodenEs handelt sich um eine randomisierte kontrollierte Studie (randomized controlled trial, RCT), bei der 114 Teilnehmerinnen der Shanghai University of Traditional Chinese Medicine, die die Einschlusskriterien erfüllen, im Verhältnis 1:1 in zwei Gruppen aufgeteilt werden. Die Interventionsgruppe erhält Tuina in Kombination mit chinesischen Kräuterkompressen, während die Kontrollgruppe nur eine Behandlung mit chinesischen Kräuterkompressen erhält. Die Behandlung erfolgt drei Tage vor der Menstruation (einmal täglich, dreimal pro Menstruationszyklus). Das primäre Zielkriterium wird anhand der visuellen Analogskala (VAS) gemessen. Die sekundären Zielkriterien werden mithilfe des Dysmenorrhoe-Symptom-Scores, des chinesischen medizinischen Dysmenorrhoe-Symptom-Scores, der Self-rating Anxiety Scale (SAS), der Self-rating Depression Scale (SDS) und der Schmerzschwelle am Guanyuan-Akupunkturpunkt (CV4) ermittelt.SchlussfolgerungDiese Studie ist die erste randomisierte kontrollierte Studie, die die Kombination von Tuina und chinesischen Kräuterkompressen zur Behandlung von PD in der Kategorie Kältekoagulation und Blutstauungssyndrom untersucht. Sollten die Ergebnisse zeigen, dass Tuina in Kombination mit chinesischen Kräuterkompressen wirksam ist, erwarten wir, dass diese Studie evidenzbasierte Belege für eine mögliche alternative Behandlung von PD in der Zukunft liefern wird.}, } @article {pmid38010626, year = {2024}, author = {Zhong, R and Rua, MT and Wei-LaPierre, L}, title = {Targeting mitochondrial Ca[2+] uptake for the treatment of amyotrophic lateral sclerosis.}, journal = {The Journal of physiology}, volume = {602}, number = {8}, pages = {1519-1549}, pmid = {38010626}, issn = {1469-7793}, support = {R01 NS127858/NS/NINDS NIH HHS/United States ; R21 NS099545/NS/NINDS NIH HHS/United States ; R56 NS117429/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Humans ; *Amyotrophic Lateral Sclerosis/pathology ; Calcium/metabolism ; *Neurodegenerative Diseases ; Motor Neurons/physiology ; Mitochondria/metabolism ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a rare adult-onset neurodegenerative disease characterized by progressive motor neuron (MN) loss, muscle denervation and paralysis. Over the past several decades, researchers have made tremendous efforts to understand the pathogenic mechanisms underpinning ALS, with much yet to be resolved. ALS is described as a non-cell autonomous condition with pathology detected in both MNs and non-neuronal cells, such as glial cells and skeletal muscle. Studies in ALS patient and animal models reveal ubiquitous abnormalities in mitochondrial structure and function, and disturbance of intracellular calcium homeostasis in various tissue types, suggesting a pivotal role of aberrant mitochondrial calcium uptake and dysfunctional calcium signalling cascades in ALS pathogenesis. Calcium signalling and mitochondrial dysfunction are intricately related to the manifestation of cell death contributing to MN loss and skeletal muscle dysfunction. In this review, we discuss the potential contribution of intracellular calcium signalling, particularly mitochondrial calcium uptake, in ALS pathogenesis. Functional consequences of excessive mitochondrial calcium uptake and possible therapeutic strategies targeting mitochondrial calcium uptake or the mitochondrial calcium uniporter, the main channel mediating mitochondrial calcium influx, are also discussed.}, } @article {pmid38010108, year = {2024}, author = {Hincelin-Mery, A and Nicolas, X and Cantalloube, C and Pomponio, R and Lewanczyk, P and Benamor, M and Ofengeim, D and Krupka, E and Hsiao-Nakamoto, J and Eastenson, A and Atassi, N}, title = {Safety, pharmacokinetics, and target engagement of a brain penetrant RIPK1 inhibitor, SAR443820 (DNL788), in healthy adult participants.}, journal = {Clinical and translational science}, volume = {17}, number = {1}, pages = {e13690}, pmid = {38010108}, issn = {1752-8062}, mesh = {Adult ; Humans ; Healthy Volunteers ; Dose-Response Relationship, Drug ; Area Under Curve ; Half-Life ; Double-Blind Method ; *Brain ; *Receptor-Interacting Protein Serine-Threonine Kinases ; }, abstract = {SAR443820 (DNL788) is a selective, orally bioavailable, brain penetrant inhibitor of receptor-interacting serine/threonine protein kinase 1 (RIPK1). This phase I first-in-human healthy participant study (NCT05795907) was comprised of three parts: randomized, double-blind, placebo-controlled single ascending dose (SAD; part 1a); 14-day multiple ascending dose (MAD; part 2) parts that evaluated safety, tolerability, pharmacokinetics (PK), and pharmacodynamics of SAR443820; and a separate open-label, single-dose part 1b (PK-cerebrospinal fluid [CSF]) to assess SAR443820 levels in CSF. SAR443820 was well-tolerated in healthy participants, and no treatment discontinuation related to an adverse event (AE) occurred. Most common AEs were dizziness and headache. No clinically meaningful changes were noted in laboratory values, vital signs, or electrocardiogram parameters. SAR443820 had a favorable PK profile, with plasma half-lives (geometric mean) ranged between 5.7-8.0 h and 7.2-8.9 h after single and repeated doses, respectively. There were no major deviations from dose proportionality for maximum concentration and area under the curve across SAR443820 doses. Mean CSF-to-unbound plasma concentration ratio ranged from 0.8 to 1.3 over time (assessed up to 10 h postdose), indicating high brain penetrance. High levels of inhibition of activated RIPK1, as measured by decrease in pS166-RIPK1, were achieved in both SAD and MAD parts, with a maximum median inhibition from baseline close to 90% at predose (Ctrough) after multiple dosing in MAD, reflecting a marked RIPK1 target engagement at the peripheral level. These results support further development of SAR443820 in phase II trials in amyotrophic lateral sclerosis (NCT05237284) and multiple sclerosis (NCT05630547).}, } @article {pmid38009843, year = {2024}, author = {Cykowski, MD and Arumanayagam, AS and Powell, SZ and Appel, SH}, title = {Primary visual cortex pathology in ALS patients with C9ORF72 expansion.}, journal = {Brain pathology (Zurich, Switzerland)}, volume = {34}, number = {5}, pages = {e13229}, pmid = {38009843}, issn = {1750-3639}, support = {RF1 NS118584/NS/NINDS NIH HHS/United States ; RF1NS118584/NS/NINDS NIH HHS/United States ; 19-IIA-465//ALS Association/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/pathology ; *C9orf72 Protein/genetics ; Middle Aged ; Female ; Male ; DNA Repeat Expansion ; Primary Visual Cortex/pathology ; Aged ; Proteins/genetics/metabolism ; }, abstract = {Poly-GA and poly-GP immunofluorescence studies show conspicuous dipeptide repeat pathology in layers IV and II of primary visual cortex in C9ALS patients.}, } @article {pmid38008627, year = {2024}, author = {Zhang, J and Wang, C and Zhou, M and Wang, Z}, title = {Comprehensive treatment of amyotrophic lateral sclerosis combined with colon cancer: A case report.}, journal = {Asian journal of surgery}, volume = {47}, number = {2}, pages = {1274-1275}, doi = {10.1016/j.asjsur.2023.11.063}, pmid = {38008627}, issn = {0219-3108}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis ; *Colonic Neoplasms ; }, } @article {pmid38008074, year = {2024}, author = {Saha, S and Singh, R and Mani, I and Chakraborty, K and Sarkar, P and Saha, S and Rana, A and Chattopadhyay, R}, title = {Individualized Homeopathic Medicines in the Treatment of Post-COVID-19 Fatigue in Adults: Single-Blind, Randomized, Placebo-Controlled Trial.}, journal = {Complementary medicine research}, volume = {31}, number = {1}, pages = {1-9}, doi = {10.1159/000535279}, pmid = {38008074}, issn = {2504-2106}, mesh = {Adult ; Humans ; *COVID-19/therapy ; India ; *Materia Medica ; Quality of Life ; Single-Blind Method ; Sulfur ; }, abstract = {INTRODUCTION: The coronavirus disease 2019 (COVID-19) is leading to unknown and unusual health conditions that are challenging to manage. Post-COVID-19 fatigue is one of those challenges, becoming increasingly common as the pandemic evolves, as it impairs the quality of life of an individual. This trial attempts to identify the preliminary evidence of the efficacy of individualized homeopathic medicines (IHMs) against placebos in the treatment of post-COVID-19 fatigue in adults.

METHODS: A 3-month, single-blind, randomized, placebo-controlled, parallel-arm trial was conducted at the outpatient department of The Calcutta Homoeopathic Medical College and Hospital, India. Sixty participants were randomized in a 1:1 ratio to receive either IHMs (n = 30) or identical-looking placebos (n = 30). The primary and secondary outcome measures were the Fatigue Assessment Scale (FAS) and Outcome in Relation to Impact on Daily Living (ORIDL), respectively, measured every month, for up to 3 months. Comparative analysis was carried out on the intention-to-treat sample to detect group differences.

RESULTS: Group differences in both the primary (FAS total: F1, 58 = 14.356, p < 0.001) and secondary outcomes (ORIDL: F1, 58 = 210.986, p < 0.001) after 3 months favored IHMs against placebos. Lycopodium clavatum (11.7%), sulfur (11.7%), Arsenicum album (10%), and Thuja occidentalis (10%) were the most frequently indicated medicines. No harm, unintended effects, homeopathic aggravations, or any serious adverse events were reported from either of the groups.

CONCLUSION: IHMs produced significantly better effects than placebos in the treatment of post-COVID-19 fatigue in adults. Definitive robust trials may be undertaken to confirm the findings.

UNLABELLED: EinleitungDie Coronainfektion (COVID-19) zieht unbekannte und ungewöhnliche gesundheitliche Probleme nach sich, deren Management oft eine Herausforderung darstellt. Das gilt unter anderem für Ermüdung nach einer COVID-19-Erkrankung, die mit zunehmender Dauer der Pandemie immer häufiger auftritt und die Lebensqualität der Betroffenen beeinträchtigt. In dieser Studie wird versucht, vorläufige Belege für die Wirksamkeit individualisierter homöopathischer Mittel (IHM) im Vergleich zu Placebo zur Behandlung von Ermüdung nach COVID-19 bei Erwachsenen zu identifizieren.MethodenEine einfach verblindete, randomisierte, placebokontrollierte Parallelgruppenstudie von 3 Monaten Dauer wurde im ambulanten Bereich des Calcutta Homoeopathic Medical College and Hospital in Indien durchgeführt. 60 Teilnehmer erhielten nach Randomisierung im Verhältnis 1:1 entweder IHM (n = 30) oder identisch aussehendes Placebo (n = 30). Die primäre und die sekundäre Zielgröße waren die Fatigue Assessment Scale (FAS) und das Outcome in Relation to Impact on Daily Living (ORIDL) für bis zu 3 Monate, jeweils monatlich gemessen. Vergleichende Analysen wurden an der Intent-to-treat-Population durchgeführt, um Unterschiede zwischen den Gruppen zu erkennen.ErgebnisseGruppenunterschiede bei der primären (FAS gesamt: F1, 58 = 14,356; p < 0.001) sowie der sekundären Zielgröße (ORIDL: F1, 58 = 210,986; p < 0.001) nach 3 Monaten sprachen für die IHM gegenüber Placebo. Lycopodium clavatum (11.7%), sulfur (11.7%), Arsenicum album (10%) und Thuja occidentalis (10%) waren die am häufigsten indizierten Mittel. In beiden Gruppen wurden keine Schädigungen, unbeabsichtigten Wirkungen, homöopathischen Verschlechterungen oder jegliche schwerwiegenden unerwünschten Ereignisse beobachtet.SchlussfolgerungDie IHM erzielten signifikant bessere Effekte als Placebo in der Behandlung von Post-COVID-Ermüdung bei Erwachsenen. Definitive, belastbare Studien können eingeleitet werden, um diese Befunde zu bestätigen.}, } @article {pmid38008065, year = {2024}, author = {Maier, GS and Rosar, G and Dietz, G and Hemken, N and Kafchitsas, K and Seeger, JB and Horas, K}, title = {Effectiveness of Mud-Pack Therapy and Mud-Bath Therapy in Osteoarthritis: A Systematic Review.}, journal = {Complementary medicine research}, volume = {31}, number = {1}, pages = {30-39}, doi = {10.1159/000535437}, pmid = {38008065}, issn = {2504-2106}, mesh = {Humans ; *Mud Therapy ; *Osteoarthritis, Knee ; *Osteoarthritis, Hip ; Quality of Life ; *Low Back Pain ; }, abstract = {OBJECTIVES: Osteoarthritis has a tremendous socioeconomic impact in terms of drug spending, hospital admissions, work productivity, and temporary or permanent incapacity. Mud therapy has been discussed as potential conservative treatment options for osteoarthritis. However, findings from several trials still remain controversial. For this reason, we aimed to systematically review the highest evidence provided by published trials to estimate the clinical effect of mud-pack and mud-bath therapy for the treatment of osteoarthritis.

METHODS: We searched PubMed, PEDro, and the Cochrane CENTRAL Register for Controlled Trials for articles published between 2000 and 2020 using the terms "orthopedics," "orthopaedics," "musculoskeletal," "osteoarthritis," and "mud bath," "mud pack."

RESULTS: Of the 19 studies included, 15 examined the effects of mud-bath therapy in knee osteoarthritis treatment. One study focused on the treatment effect of mud bath on hand osteoarthritis, another study examined treatment effects in hip and knee osteoarthritis, and two studies enrolled patients with chronic low back pain caused by lumbar spine osteoarthritis. We systematically reviewed the data obtained from the literature and summarized the results on the basis of the main outcomes. The results show significant improvements in function, quality of life, and perceived pain for patients with osteoarthritis.

CONCLUSION: Results of randomized controlled trials suggest that mud therapy is part of a promising integrated and synergistic multidisciplinary approach in combination with other treatment forms like pharmacotherapy or physiotherapy.

UNLABELLED: ZieleDie sozio-ökonomischen Auswirkungen der Arthrose sind immens. Heiltorfbehandlungen sind seit einiger Zeit als mögliche Ergänzung der konservativen Therapieoptionen dieser Erkrankung Gegenstand wissenschaftlicher Untersuchungen. Ziel dieser Studie war es, die aktuellen Erkenntnisse zur Heiltorftherapie bei Arthrose zusammenzufassen.MethodenWir führten eine systematische Literaturrecherche der Datenbanken Pubmed, PEDro und Cochrane CENTRAL Register of Controlled Trials durch. Hierbei wurden Artikel, die zwischen 2000 und 2020 publiziert wurden und mit den Schlagwörtern “orthopedics”, “orthopaedics”, “musculoskeletal”, “osteoarthritis” und “mud-bath”, “mud-pack” assoziiert waren, erfasst.ErgebnisseVon den 19 näher untersuchten Studien beschäftigten sich 15 mit den Effekten der Heiltorftherapie bei Patienten mit Kniearthrose, eine Studie untersuchte Patienten mit Arthrose der Hand, eine weitere Studie untersuchte die Auswirkung der Therapie bei Arthrose der Hüfte. 2 Studien untersuchten den Effekt der Moorbäder bei Patienten mit chronischen Rückenschmerzen. Insgesamt zeigten sich signifikante Verbesserungen der Funktion, Lebensqualität und Schmerzlinderung bei den Patienten unter Heiltorftherapie.ZusammenfassungDie Ergebnisse der randomisierten, kontrollierten Studien zeigen, dass die Heiltorftherapie eine vielversprechende Ergänzung in einem multidisziplinären Ansatz der Arthrosetherapie ist.}, } @article {pmid38007795, year = {2023}, author = {Feng, T}, title = {Applications of Artificial Intelligence to Diagnosis of Neurodegenerative Diseases.}, journal = {Studies in health technology and informatics}, volume = {308}, number = {}, pages = {648-655}, doi = {10.3233/SHTI230896}, pmid = {38007795}, issn = {1879-8365}, mesh = {Humans ; Artificial Intelligence ; *Neurodegenerative Diseases/diagnostic imaging ; *Alzheimer Disease/diagnostic imaging ; Machine Learning ; Natural Language Processing ; }, abstract = {Artificial Intelligence (AI) is an umbrella term that represents a new technology for simulating and expanding human intelligence by using machines and computer systems. It consists of methods such as machine learning (ML), deep learning (DL), and natural language processing (NLP). In the era of big data, AI has emerged as an essential tool for improving the detection of neurodegenerative diseases, such as Alzheimer's diseases (AD), Parkinson's diseases, amyotrophic lateral sclerosis, etc. AI with its ability to extract critical information from the mass of data has enabled scientists to deal with various types of large-volume data, including genetic data, imaging data, and clinical data, rapidly generated in the course of neurodegenerative disease research. This review provides a comprehensive overview of the literature on current AI applications in the diagnosis of neurodegenerative diseases. Firstly, bioinformatics and AI approaches to identify potential biomarkers for neurodegenerative diseases such as AD are reviewed. Secondly, the use of ML and DL methods to analyze Magnetic Resonance Imaging (MRI) data for a better understanding of disease progression and predicting patient outcomes is discussed. Finally, the use of AI methods including NLP for Electronic Health Record (EHR) data analysis to extract meaningful information and identify patterns that may contribute to early diagnosis and treatment planning are reviewed. The potential benefits of AI-based approaches in improving patient outcomes and the challenges associated with their implementations are also discussed. Overall, this paper highlights the promise of AI in transforming the diagnosis and management of neurodegenerative diseases.}, } @article {pmid38007141, year = {2024}, author = {Wong, CH and Rahat, A and Chang, HC}, title = {Fused in sarcoma regulates glutamate signaling and oxidative stress response.}, journal = {Free radical biology & medicine}, volume = {210}, number = {}, pages = {172-182}, pmid = {38007141}, issn = {1873-4596}, support = {P40 OD010440/OD/NIH HHS/United States ; R01 GM131156/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Humans ; *Amyotrophic Lateral Sclerosis/genetics/pathology ; Caenorhabditis elegans/metabolism ; Glutamates/metabolism ; Mutation ; Oxidation-Reduction ; Oxidative Stress/genetics ; Superoxide Dismutase/genetics/metabolism ; Superoxide Dismutase-1/genetics ; Disease Models, Animal ; *RNA-Binding Protein FUS/genetics/metabolism ; Caenorhabditis elegans Proteins/genetics/metabolism ; }, abstract = {Mutations in fused in sarcoma (fust-1) are linked to ALS. However, how these ALS causative mutations alter physiological processes and lead to the onset of ALS remains largely unknown. By obtaining humanized fust-1 ALS mutations via CRISPR-CAS9, we generated a C. elegans ALS model. Homozygous fust-1 ALS mutant and fust-1 deletion animals are viable in C. elegans. This allows us to better characterize the molecular mechanisms of fust-1-dependent responses. We found FUST-1 plays a role in regulating superoxide dismutase, glutamate signaling, and oxidative stress. FUST-1 suppresses SOD-1 and VGLUT/EAT-4 in the nervous system. FUST-1 also regulates synaptic AMPA-type glutamate receptor GLR-1. We found that fust-1 ALS mutations act as loss-of-function in SOD-1 and VGLUT/EAT-4 phenotypes, whereas the fust-1 ALS mutations act as gain-of-function in redox homeostasis and the microbe-induced oxidative stress response. We hypothesized that FUST-1 is a link between glutamate signaling and SOD-1. Our results may provide new insights into the human ALS alleles and their roles in pathological mechanisms that lead to ALS.}, } @article {pmid38006254, year = {2024}, author = {Kabir, V and Ombelet, F and Hobin, F and Lamaire, N and De Vocht, J and Van Damme, P}, title = {Prognostic value of motor and extramotor involvement in ALS.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {25}, number = {1-2}, pages = {67-74}, doi = {10.1080/21678421.2023.2284899}, pmid = {38006254}, issn = {2167-9223}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/complications/diagnosis/epidemiology ; *Frontotemporal Dementia/complications/diagnosis/psychology ; Cohort Studies ; Prognosis ; Retrospective Studies ; }, abstract = {OBJECTIVE: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder resulting in upper and lower motor neuron loss. ALS often has a focal onset of weakness, which subsequently spreads to other body regions. Survival is limited to two to five years after disease onset, often due to respiratory failure. Cognitive impairment is present in approximately 30% to 50% of patients and in 10%-15% of patients, the clinical criteria of frontotemporal dementia (FTD) are met.

METHODS: In this retrospective single-center ALS cohort study, we examined the occurrence of cognitive and behavioral impairment in relation to motor impairment at disease presentation and studied its impact on survival.

RESULTS: The degree of lower motor neuron involvement was associated with a worse survival, but there was no effect for upper motor neuron involvement. Patients who were cognitively normal had a significantly better survival compared to patients with cognitive or behavioral impairment and to patients with comorbid FTD. There was no significant difference regarding survival between patients with FTD and patients with cognitive or behavioral impairment.

CONCLUSIONS: The extent of motor and extramotor involvement in patients with ALS at disease presentation holds complementary prognostic information.}, } @article {pmid38005489, year = {2023}, author = {Li, J and Liang, W and Yin, X and Li, J and Guan, W}, title = {Multimodal Gait Abnormality Recognition Using a Convolutional Neural Network-Bidirectional Long Short-Term Memory (CNN-BiLSTM) Network Based on Multi-Sensor Data Fusion.}, journal = {Sensors (Basel, Switzerland)}, volume = {23}, number = {22}, pages = {}, pmid = {38005489}, issn = {1424-8220}, support = {No. 2021AAA007//Department of Science and Technology of Hubei Province/ ; }, mesh = {Humans ; *Parkinson Disease/diagnosis ; *Amyotrophic Lateral Sclerosis ; Neural Networks, Computer ; Gait ; *Huntington Disease ; }, abstract = {Global aging leads to a surge in neurological diseases. Quantitative gait analysis for the early detection of neurological diseases can effectively reduce the impact of the diseases. Recently, extensive research has focused on gait-abnormality-recognition algorithms using a single type of portable sensor. However, these studies are limited by the sensor's type and the task specificity, constraining the widespread application of quantitative gait recognition. In this study, we propose a multimodal gait-abnormality-recognition framework based on a Convolutional Neural Network-Bidirectional Long Short-Term Memory (CNN-BiLSTM) network. The as-established framework effectively addresses the challenges arising from smooth data interference and lengthy time series by employing an adaptive sliding window technique. Then, we convert the time series into time-frequency plots to capture the characteristic variations in different abnormality gaits and achieve a unified representation of the multiple data types. This makes our signal processing method adaptable to several types of sensors. Additionally, we use a pre-trained Deep Convolutional Neural Network (DCNN) for feature extraction, and the consequently established CNN-BiLSTM network can achieve high-accuracy recognition by fusing and classifying the multi-sensor input data. To validate the proposed method, we conducted diversified experiments to recognize the gait abnormalities caused by different neuropathic diseases, such as amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), and Huntington's disease (HD). In the PDgait dataset, the framework achieved an accuracy of 98.89% in the classification of Parkinson's disease severity, surpassing DCLSTM's 96.71%. Moreover, the recognition accuracy of ALS, PD, and HD on the PDgait dataset was 100%, 96.97%, and 95.43% respectively, surpassing the majority of previously reported methods. These experimental results strongly demonstrate the potential of the proposed multimodal framework for gait abnormality identification. Due to the advantages of the framework, such as its suitability for different types of sensors and fewer training parameters, it is more suitable for gait monitoring in daily life and the customization of medical rehabilitation schedules, which will help more patients alleviate the harm caused by their diseases.}, } @article {pmid38005288, year = {2023}, author = {Lapshina, MA and Shevtsova, EF and Grigoriev, VV and Aksinenko, AY and Ustyugov, AA and Steinberg, DA and Maleev, GV and Dubrovskaya, ES and Goreva, TV and Epishina, TA and Zamoyski, VL and Makhaeva, GF and Fisenko, VP and Veselov, IM and Vinogradova, DV and Bachurin, SO}, title = {New Adamantane-Containing Edaravone Conjugates as Potential Neuroprotective Agents for ALS Treatments.}, journal = {Molecules (Basel, Switzerland)}, volume = {28}, number = {22}, pages = {}, pmid = {38005288}, issn = {1420-3049}, support = {19-13-00378-P//Russian Science Foundation/ ; }, mesh = {Humans ; Edaravone/pharmacology/therapeutic use ; *Neuroprotective Agents/pharmacology/therapeutic use ; *Amyotrophic Lateral Sclerosis/drug therapy ; *Adamantane ; Riluzole ; Amantadine/therapeutic use ; }, abstract = {Currently, there are no effective drugs for the treatment of amyotrophic lateral sclerosis (ALS). Only two drugs-edaravone and riluzole-have been approved, but they have very limited efficacy. The aim of this work was to modify the structural core of the Edaravone-phenylpyrazolone moiety and combine it with aminoadamantane pharmacophore in order to expand the spectrum of its action to a number of processes involved in the pathogenesis of ALS. New conjugates of edaravone derivatives with 1-aminoadamantanes combined with alkylene or hydroxypropylene spacers were synthesized, and their biological activity was investigated. Compounds were found that could inhibit lipid peroxidation and calcium-related mitochondrial permeability, block fast sodium currents of CNS neurons, and reduce aggregation of the mutated form of the FUS-protein typical to ALS. So, the proposed modification of the edaravone molecule has allowed the obtaining of new original structures that combine some prospective therapeutic mechanisms against key chains of the pathogenesis of ALS. The identified lead compounds can be used for further optimization and development of new promising drugs on this basis for the treatment of ALS.}, } @article {pmid38004577, year = {2023}, author = {Niazi, SK}, title = {Non-Invasive Drug Delivery across the Blood-Brain Barrier: A Prospective Analysis.}, journal = {Pharmaceutics}, volume = {15}, number = {11}, pages = {}, pmid = {38004577}, issn = {1999-4923}, abstract = {Non-invasive drug delivery across the blood-brain barrier (BBB) represents a significant advancement in treating neurological diseases. The BBB is a tightly packed layer of endothelial cells that shields the brain from harmful substances in the blood, allowing necessary nutrients to pass through. It is a highly selective barrier, which poses a challenge to delivering therapeutic agents into the brain. Several non-invasive procedures and devices have been developed or are currently being investigated to enhance drug delivery across the BBB. This paper presents a review and a prospective analysis of the art and science that address pharmacology, technology, delivery systems, regulatory approval, ethical concerns, and future possibilities.}, } @article {pmid38003404, year = {2023}, author = {Huang, B and Liu, X and Zhang, T and Wu, Q and Huang, C and Xia, XG and Zhou, H}, title = {Increase in hnRNPA1 Expression Suffices to Kill Motor Neurons in Transgenic Rats.}, journal = {International journal of molecular sciences}, volume = {24}, number = {22}, pages = {}, pmid = {38003404}, issn = {1422-0067}, support = {R01 NS089701/NS/NINDS NIH HHS/United States ; R01 NS095962/NS/NINDS NIH HHS/United States ; R01 NS110455/NS/NINDS NIH HHS/United States ; NS089701, NS095962, NS110455/NS/NINDS NIH HHS/United States ; }, mesh = {Rats ; Animals ; Mice ; *Amyotrophic Lateral Sclerosis/metabolism ; Rats, Transgenic ; Motor Neurons/metabolism ; Phenotype ; Mutation ; Mice, Transgenic ; Disease Models, Animal ; Superoxide Dismutase-1/genetics ; }, abstract = {A dominant mutation in hnRNPA1 causes amyotrophic lateral sclerosis (ALS), but it is not known whether this mutation leads to motor neuron death through increased or decreased function. To elucidate the relationship between pathogenic hnRNPA1 mutation and its native function, we created novel transgenic rats that overexpressed wildtype rat hnRNPA1 exclusively in motor neurons. This targeted expression of wildtype hnRNPA1 caused severe motor neuron loss and subsequent denervation muscle atrophy in transgenic rats that recapitulated the characteristics of ALS. These findings demonstrate that the augmentation of hnRNPA1 expression suffices to trigger motor neuron degeneration and the manifestation of ALS-like phenotypes. It is reasonable to infer that an amplification of an as-yet undetermined hnRNPA1 function plays a pivotal role in the pathogenesis of familial ALS caused by pathogenic hnRNPA1 mutation.}, } @article {pmid38003309, year = {2023}, author = {Toader, C and Dobrin, N and Brehar, FM and Popa, C and Covache-Busuioc, RA and Glavan, LA and Costin, HP and Bratu, BG and Corlatescu, AD and Popa, AA and Ciurea, AV}, title = {From Recognition to Remedy: The Significance of Biomarkers in Neurodegenerative Disease Pathology.}, journal = {International journal of molecular sciences}, volume = {24}, number = {22}, pages = {}, pmid = {38003309}, issn = {1422-0067}, mesh = {Humans ; *Neurodegenerative Diseases/diagnosis/metabolism ; *Amyotrophic Lateral Sclerosis ; *Parkinson Disease/diagnosis/metabolism ; *Alzheimer Disease/diagnosis ; Biomarkers/metabolism ; }, abstract = {With the inexorable aging of the global populace, neurodegenerative diseases (NDs) like Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS) pose escalating challenges, which are underscored by their socioeconomic repercussions. A pivotal aspect in addressing these challenges lies in the elucidation and application of biomarkers for timely diagnosis, vigilant monitoring, and effective treatment modalities. This review delineates the quintessence of biomarkers in the realm of NDs, elucidating various classifications and their indispensable roles. Particularly, the quest for novel biomarkers in AD, transcending traditional markers in PD, and the frontier of biomarker research in ALS are scrutinized. Emergent susceptibility and trait markers herald a new era of personalized medicine, promising enhanced treatment initiation especially in cases of SOD1-ALS. The discourse extends to diagnostic and state markers, revolutionizing early detection and monitoring, alongside progression markers that unveil the trajectory of NDs, propelling forward the potential for tailored interventions. The synergy between burgeoning technologies and innovative techniques like -omics, histologic assessments, and imaging is spotlighted, underscoring their pivotal roles in biomarker discovery. Reflecting on the progress hitherto, the review underscores the exigent need for multidisciplinary collaborations to surmount the challenges ahead, accelerate biomarker discovery, and herald a new epoch of understanding and managing NDs. Through a panoramic lens, this article endeavors to provide a comprehensive insight into the burgeoning field of biomarkers in NDs, spotlighting the promise they hold in transforming the diagnostic landscape, enhancing disease management, and illuminating the pathway toward efficacious therapeutic interventions.}, } @article {pmid38003212, year = {2023}, author = {Lovatto, M and Gonçalves-Vidigal, MC and Vaz Bisneta, M and Calvi, AC and Mazucheli, J and Vidigal Filho, PS and Miranda, EGR and Melotto, M}, title = {Responsiveness of Candidate Genes on CoPv01[CDRK]/PhgPv01[CD][RK] Loci in Common Bean Challenged by Anthracnose and Angular Leaf Spot Pathogens.}, journal = {International journal of molecular sciences}, volume = {24}, number = {22}, pages = {}, pmid = {38003212}, issn = {1422-0067}, support = {408472/2018-9//National Council for Scientific and Technological Development/ ; BEX 88881.170662//2018-01//Coordenação de Aperfeicoamento de Pessoal de Nível Superior/ ; }, mesh = {Chromosome Mapping ; *Colletotrichum/genetics ; Disease Resistance/genetics ; Genetic Linkage ; Genetic Markers ; Kidney ; *Phaseolus/genetics ; Plant Diseases/genetics ; }, abstract = {Anthracnose (ANT) and angular leaf spot (ALS) are significant diseases in common bean, leading to considerable yield losses under specific environmental conditions. The California Dark Red Kidney (CDRK) bean cultivar is known for its resistance to multiple races of both pathogens. Previous studies have identified the CoPv01[CDRK]/PhgPv01[CDRK] resistance loci on chromosome Pv01. Here, we evaluated the expression levels of ten candidate genes near the CoPv01[CDRK]/PhgPv01[CDRK] loci and plant defense genes using quantitative real-time PCR in CDRK cultivar inoculated with races 73 of Colletotrichum lindemuthianum and 63-39 of Pseudocercospora griseola. Gene expression analysis revealed that the Phvul.001G246300 gene exhibited the most elevated levels, showing remarkable 7.8-fold and 8.5-fold increases for ANT and ALS, respectively. The Phvul.001G246300 gene encodes an abscisic acid (ABA) receptor with pyrabactin resistance, PYR1-like (PYL) protein, which plays a central role in the crosstalk between ABA and jasmonic acid responses. Interestingly, our results also showed that the other defense genes were initially activated. These findings provide critical insights into the molecular mechanisms underlying plant defense against these diseases and could contribute to the development of more effective disease management strategies in the future.}, } @article {pmid38002982, year = {2023}, author = {Lombardi, M and Corrado, L and Piola, B and Comi, C and Cantello, R and D'Alfonso, S and Mazzini, L and De Marchi, F}, title = {Variability in Clinical Phenotype in TARDBP Mutations: Amyotrophic Lateral Sclerosis Case Description and Literature Review.}, journal = {Genes}, volume = {14}, number = {11}, pages = {}, pmid = {38002982}, issn = {2073-4425}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/metabolism ; DNA-Binding Proteins/genetics/metabolism ; Italy ; Mutation ; Phenotype ; }, abstract = {Mutations in the 43 kDa transactive-response (TAR)-DNA-binding protein (TARDBP) are associated with 2-5% of familial Amyotrophic Lateral Sclerosis (ALS) cases. TAR DNA-Binding Protein 43 (TDP-43) is an RNA/DNA-binding protein involved in several cellular mechanisms (e.g., transcription, pre-mRNA processing, and splicing). Many ALS-linked TARDBP mutations have been described in the literature, but few phenotypic data on monogenic TARDBP-mutated ALS are available. In this paper, (1) we describe the clinical features of ALS patients carrying mutations in the TARDBP gene evaluated at the Tertiary ALS Center at Maggiore della Carità University Hospital, Novara, Italy, from 2010 to 2020 and (2) present the results of our review of the literature on this topic, analyzing data obtained for 267 patients and highlighting their main clinical and demographic features.}, } @article {pmid38002967, year = {2023}, author = {Tourtourikov, I and Dabchev, K and Todorov, T and Angelov, T and Chamova, T and Tournev, I and Kadiyska, T and Mitev, V and Todorova, A}, title = {Navigating the ALS Genetic Labyrinth: The Role of MAPT Haplotypes.}, journal = {Genes}, volume = {14}, number = {11}, pages = {}, pmid = {38002967}, issn = {2073-4425}, support = {D-186/ 14.06.2022//Medical University Sofia/ ; }, mesh = {Humans ; Haplotypes ; *Amyotrophic Lateral Sclerosis/genetics ; tau Proteins/genetics ; *Neurodegenerative Diseases ; Genetic Predisposition to Disease ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by wide clinical and biological heterogeneity, with a large proportion of ALS patients also exhibiting frontotemporal dementia (FTD) spectrum symptoms. This project aimed to characterize risk subtypes of the H1 haplotype within the MAPT (microtubule-associated protein tau) gene, according to their possible effect as a risk factor and as a modifying factor in relation to the age of disease onset. One hundred patients from Bulgaria with sporadic ALS were genotyped for the variants rs1467967, rs242557, rs1800547, rs3785883, rs2471738, and rs7521. Haploview 4.2 and SHEsisPlus were used to reconstruct haplotype frequencies using genotyping data from the 1000 Genomes project as controls. Genotype-phenotype correlation was investigated in the context of age of disease onset and risk of disease development. While the individual variants of the subtypes do not influence the age of onset of the disease, a correlation was found between the specific haplotype GGAGCA (H1b) and the risk of developing sALS, with results showing that individuals harboring this haplotype have a nearly two-fold increased risk of developing sALS compared to other H1 subtypes. The results from this study suggest that fine transcriptional regulation at the MAPT locus can influence the risk of ALS.}, } @article {pmid38002924, year = {2023}, author = {Genin, EC and Abou-Ali, M and Paquis-Flucklinger, V}, title = {Mitochondria, a Key Target in Amyotrophic Lateral Sclerosis Pathogenesis.}, journal = {Genes}, volume = {14}, number = {11}, pages = {}, pmid = {38002924}, issn = {2073-4425}, support = {ANR-16-CE16-0024-01//Agence Nationale de la Recherche/ ; MND202004011475//Fondation pour la Recherche Médicale/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/pathology ; Mitochondria/metabolism ; Motor Neurons/metabolism ; Cell Death/genetics ; Mitochondrial Proteins/genetics/metabolism ; }, abstract = {Mitochondrial dysfunction occurs in numerous neurodegenerative diseases, particularly amyotrophic lateral sclerosis (ALS), where it contributes to motor neuron (MN) death. Of all the factors involved in ALS, mitochondria have been considered as a major player, as secondary mitochondrial dysfunction has been found in various models and patients. Abnormal mitochondrial morphology, defects in mitochondrial dynamics, altered activities of respiratory chain enzymes and increased production of reactive oxygen species have been described. Moreover, the identification of CHCHD10 variants in ALS patients was the first genetic evidence that a mitochondrial defect may be a primary cause of MN damage and directly links mitochondrial dysfunction to the pathogenesis of ALS. In this review, we focus on the role of mitochondria in ALS and highlight the pathogenic variants of ALS genes associated with impaired mitochondrial functions. The multiple pathways demonstrated in ALS pathogenesis suggest that all converge to a common endpoint leading to MN loss. This may explain the disappointing results obtained with treatments targeting a single pathological process. Fighting against mitochondrial dysfunction appears to be a promising avenue for developing combined therapies in the future.}, } @article {pmid38002659, year = {2023}, author = {O'Day, DH}, title = {Protein Biomarkers Shared by Multiple Neurodegenerative Diseases Are Calmodulin-Binding Proteins Offering Novel and Potentially Universal Therapeutic Targets.}, journal = {Journal of clinical medicine}, volume = {12}, number = {22}, pages = {}, pmid = {38002659}, issn = {2077-0383}, abstract = {Seven major neurodegenerative diseases and their variants share many overlapping biomarkers that are calmodulin-binding proteins: Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), frontotemporal lobar dementia (FTD), Huntington's disease (HD), Lewy body disease (LBD), multiple sclerosis (MS), and Parkinson's disease (PD). Calcium dysregulation is an early and persistent event in each of these diseases, with calmodulin serving as an initial and primary target of increased cytosolic calcium. Considering the central role of calcium dysregulation and its downstream impact on calcium signaling, calmodulin has gained interest as a major regulator of neurodegenerative events. Here, we show that calmodulin serves a critical role in neurodegenerative diseases via binding to and regulating an abundance of biomarkers, many of which are involved in multiple neurodegenerative diseases. Of special interest are the shared functions of calmodulin in the generation of protein biomarker aggregates in AD, HD, LBD, and PD, where calmodulin not only binds to amyloid beta, pTau, alpha-synuclein, and mutant huntingtin but also, via its regulation of transglutaminase 2, converts them into toxic protein aggregates. It is suggested that several calmodulin binding proteins could immediately serve as primary drug targets, while combinations of calmodulin binding proteins could provide simultaneous insight into the onset and progression of multiple neurodegenerative diseases.}, } @article {pmid38002573, year = {2023}, author = {Goto, S and Maeda, N and Uehara, K and Ogawa, K and Matsumaru, M and Sugiyama, S and Ohnuma, K and Lawu, T and Noda, T}, title = {Effect of Segmented Optical Axial Length on the Performance of New-Generation Intraocular Lens Power Calculation Formulas in Extremely Long Eyes.}, journal = {Journal of clinical medicine}, volume = {12}, number = {22}, pages = {}, pmid = {38002573}, issn = {2077-0383}, abstract = {PURPOSE: To evaluate the performance of traditional vergence formulas with segmented axial length (AL) compared to traditional composite AL in extremely long eyes, and to determine whether the segmented AL can be extended to the new-generation formulas, including the Barrett Universal II, Emmetropia Verifying Optical 2.0 (EVO2), Hill-RBF 3.0 (Hill3), Kane, and Ladas Super formula (LSF) formulas in extremely long eyes.

SETTING: National Hospital. Organization, Tokyo Medical Center, Japan.

DESIGN: Retrospective case series.

METHODS: Consecutive patients who underwent uncomplicated cataract surgery implanted with a three-piece intraocular lens between December 2015 and March 2021 were retrospectively reviewed. The composite AL was measured with a swept-source optical coherence tomography (SS-OCT) biometer using a mean refractive index. The segmented AL was calculated by summing the geometric lengths of the ocular segments (cornea, aqueous, lens, and vitreous) using multiple specific refractive indices based on the data obtained by the SS-OCT-based biometer. When refraction was measured at three months postoperatively, the median absolute errors (MedAEs) were calculated with two ALs for each formula.

RESULTS: The study included 31 eyes of 22 patients. The segmented AL (30.45 ± 1.23 mm) was significantly shorter than the composite AL (30.71 ± 1.28 mm, p < 0.001). The MedAEs were significantly reduced when using segmented AL for SRK/T, Haigis, Hill3, and LSF, compared to those obtained using composite AL (0.38 vs. 0.62, 0.48 vs. 0.79, 0.50 vs. 0.90, 0.34 vs. 0.61, p < 0.001 for all formulas, respectively). On the contrary, the MedAE obtained by Kane with segmented AL was significantly worse compared to the one with composite AL (0.35 vs. 0.27, p = 0.03).

CONCLUSION: In extremely high myopic eyes, the segmented AL improves the performance of SRK/T, Haigis, Hill3, and LSF formulas compared to the composite AL, while the segmented AL worsens the prediction accuracy of the Kane formula.}, } @article {pmid38002490, year = {2023}, author = {Yang, J and Xin, C and Huo, J and Li, X and Dong, H and Liu, Q and Li, R and Liu, Y}, title = {Rab Geranylgeranyltransferase Subunit Beta as a Potential Indicator to Assess the Progression of Amyotrophic Lateral Sclerosis.}, journal = {Brain sciences}, volume = {13}, number = {11}, pages = {}, pmid = {38002490}, issn = {2076-3425}, support = {H2021206310//Natural Science Foundation of Hebei Province/ ; }, abstract = {BACKGROUND: Currently, there is no effective treatment for amyotrophic lateral sclerosis (ALS), a devastating neurodegenerative disorder. Many biomarkers have been proposed, but because ALS is a clinically heterogeneous disease with an unclear etiology, biomarker discovery for ALS has been challenging due to the lack of specificity of these biomarkers. In recent years, the role of autophagy in the development and treatment of ALS has become a research hotspot. In our previous studies, we found that the expression of RabGGTase (low RABGGTB expression and no change in RABGGTA) is lower in the lumbar and thoracic regions of spinal cord motoneurons in SOD1G93A mice compared with WT (wild-type) mice groups, and upregulation of RABGGTB promoted prenylation modification of Rab7, which promoted autophagy to protect neurons by degrading SOD1. Given that RabGGTase is associated with autophagy and autophagy is associated with inflammation, and based on the above findings, since peripheral blood mononuclear cells are readily available from patients with ALS, we proposed to investigate the expression of RabGGTase in peripheral inflammatory cells.

METHODS: Information and venous blood were collected from 86 patients diagnosed with ALS between January 2021 and August 2023. Flow cytometry was used to detect the expression of RABGGTB in monocytes from peripheral blood samples collected from patients with ALS and healthy controls. Extracted peripheral blood mononuclear cells (PBMCs) were differentiated in vitro into macrophages, and then the expression of RABGGTB was detected by immunofluorescence. RABGGTB levels in patients with ALS were analyzed to determine their impact on disease progression.

RESULTS: Using flow cytometry in monocytes and immunofluorescence in macrophages, we found that RABGGTB expression in the ALS group was significantly higher than in the control group. Age, sex, original location, disease course, C-reactive protein (CRP), and interleukin-6 (IL-6) did not correlate with the ALS functional rating scale-revised (ALSFRS-R), whereas the RABGGTB level was significantly correlated with the ALSFRS-R. In addition, multivariate analysis revealed a significant correlation between RABGGTB and ALSFRS-R score. Further analysis revealed a significant correlation between RABGGTB expression levels and disease progression levels (ΔFS).

CONCLUSIONS: The RABGGTB level was significantly increased in patients with ALS compared with healthy controls. An elevated RABGGTB level in patients with ALS is associated with the rate of progression in ALS, suggesting that elevated RABGGTB levels in patients with ALS may serve as an indicator for tracking ALS progression.}, } @article {pmid38002405, year = {2023}, author = {Wu, CM and Chen, YJ and Chen, SC and Zheng, SF}, title = {Creating an AI-Enhanced Morse Code Translation System Based on Images for People with Severe Disabilities.}, journal = {Bioengineering (Basel, Switzerland)}, volume = {10}, number = {11}, pages = {}, pmid = {38002405}, issn = {2306-5354}, support = {NSTC 111-2221-E-167-039 and MOST 111-2221-E-218-023//the National Science and Technology Council (NSTC), Taiwan/ ; }, abstract = {(1) Background: Patients with severe physical impairments (spinal cord injury, cerebral palsy, amyotrophic lateral sclerosis) often have limited mobility due to physical limitations, and may even be bedridden all day long, losing the ability to take care of themselves. In more severe cases, the ability to speak may even be lost, making even basic communication very difficult. (2) Methods: This research will design a set of image-assistive communication equipment based on artificial intelligence to solve communication problems of daily needs. Using artificial intelligence for facial positioning, and facial-motion-recognition-generated Morse code, and then translating it into readable characters or commands, it allows users to control computer software by themselves and communicate through wireless networks or a Bluetooth protocol to control environment peripherals. (3) Results: In this study, 23 human-typed data sets were subjected to recognition using fuzzy algorithms. The average recognition rates for expert-generated data and data input by individuals with disabilities were 99.83% and 98.6%, respectively. (4) Conclusions: Through this system, users can express their thoughts and needs through their facial movements, thereby improving their quality of life and having an independent living space. Moreover, the system can be used without touching external switches, greatly improving convenience and safety.}, } @article {pmid38002264, year = {2023}, author = {Duranti, E and Villa, C}, title = {Muscle Involvement in Amyotrophic Lateral Sclerosis: Understanding the Pathogenesis and Advancing Therapeutics.}, journal = {Biomolecules}, volume = {13}, number = {11}, pages = {}, pmid = {38002264}, issn = {2218-273X}, mesh = {Animals ; Humans ; *Amyotrophic Lateral Sclerosis/therapy/pathology ; Motor Neurons/metabolism ; Muscle, Skeletal/pathology ; Muscular Atrophy/metabolism ; Paralysis/complications/pathology ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal condition characterized by the selective loss of motor neurons in the motor cortex, brainstem, and spinal cord. Muscle involvement, muscle atrophy, and subsequent paralysis are among the main features of this disease, which is defined as a neuromuscular disorder. ALS is a persistently progressive disease, and as motor neurons continue to degenerate, individuals with ALS experience a gradual decline in their ability to perform daily activities. Ultimately, muscle function loss may result in paralysis, presenting significant challenges in mobility, communication, and self-care. While the majority of ALS research has traditionally focused on pathogenic pathways in the central nervous system, there has been a great interest in muscle research. These studies were carried out on patients and animal models in order to better understand the molecular mechanisms involved and to develop therapies aimed at improving muscle function. This review summarizes the features of ALS and discusses the role of muscle, as well as examines recent studies in the development of treatments.}, } @article {pmid38001994, year = {2023}, author = {Jauregui, C and Blanco-Luquin, I and Macías, M and Roldan, M and Caballero, C and Pagola, I and Mendioroz, M and Jericó, I}, title = {Exploring the Disease-Associated Microglia State in Amyotrophic Lateral Sclerosis.}, journal = {Biomedicines}, volume = {11}, number = {11}, pages = {}, pmid = {38001994}, issn = {2227-9059}, abstract = {BACKGROUND: Neuroinflammation, and specifically microglia, plays an important but not-yet well-understood role in the pathophysiology of amyotrophic lateral sclerosis (ALS), constituting a potential therapeutic target for the disease. Recent studies have described the involvement of different microglial transcriptional patterns throughout neurodegenerative processes, identifying a new state of microglia: disease-associated microglia (DAM). The aim of this study is to investigate expression patterns of microglial-related genes in ALS spinal cord.

METHODS: We analyzed mRNA expression levels via RT-qPCR of several microglia-related genes in their homeostatic and DAM state in postmortem tissue (anterior horn of the spinal cord) from 20 subjects with ALS-TDP43 and 19 controls donors from the Navarrabiomed Biobank.

RESULTS: The expression levels of TREM2, MS4A, CD33, APOE and TYROBP were found to be elevated in the spinal cord from ALS subjects versus controls (p-value < 0.05). However, no statistically significant gene expression differences were observed for TMEM119, SPP1 and LPL.

CONCLUSIONS: This study suggests that a DAM-mediated inflammatory response is present in ALS, and TREM2 plays a significant role in immune function of microglia. It also supports the role of C33 and MS4A in the physiopathology of ALS.}, } @article {pmid38001967, year = {2023}, author = {Seki, S and Kitaoka, Y and Kawata, S and Nishiura, A and Uchihashi, T and Hiraoka, SI and Yokota, Y and Isomura, ET and Kogo, M and Tanaka, S}, title = {Characteristics of Sensory Neuron Dysfunction in Amyotrophic Lateral Sclerosis (ALS): Potential for ALS Therapy.}, journal = {Biomedicines}, volume = {11}, number = {11}, pages = {}, pmid = {38001967}, issn = {2227-9059}, support = {21K17088//JSPS KAKENHI/ ; 20H03887//JSPS KAKENHI/ ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder characterised by the progressive degeneration of motor neurons, resulting in muscle weakness, paralysis, and, ultimately, death. Presently, no effective treatment for ALS has been established. Although motor neuron dysfunction is a hallmark of ALS, emerging evidence suggests that sensory neurons are also involved in the disease. In clinical research, 30% of patients with ALS had sensory symptoms and abnormal sensory nerve conduction studies in the lower extremities. Peroneal nerve biopsies show histological abnormalities in 90% of the patients. Preclinical research has reported several genetic abnormalities in the sensory neurons of animal models of ALS, as well as in motor neurons. Furthermore, the aggregation of misfolded proteins like TAR DNA-binding protein 43 has been reported in sensory neurons. This review aims to provide a comprehensive description of ALS-related sensory neuron dysfunction, focusing on its clinical changes and underlying mechanisms. Sensory neuron abnormalities in ALS are not limited to somatosensory issues; proprioceptive sensory neurons, such as MesV and DRG neurons, have been reported to form networks with motor neurons and may be involved in motor control. Despite receiving limited attention, sensory neuron abnormalities in ALS hold potential for new therapies targeting proprioceptive sensory neurons.}, } @article {pmid38001926, year = {2023}, author = {Reddy, VP}, title = {Oxidative Stress in Health and Disease.}, journal = {Biomedicines}, volume = {11}, number = {11}, pages = {}, pmid = {38001926}, issn = {2227-9059}, abstract = {Oxidative stress, resulting from the excessive intracellular accumulation of reactive oxygen species (ROS), reactive nitrogen species (RNS), and other free radical species, contributes to the onset and progression of various diseases, including diabetes, obesity, diabetic nephropathy, diabetic neuropathy, and neurological diseases, such as Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), and Parkinson's disease (PD). Oxidative stress is also implicated in cardiovascular disease and cancer. Exacerbated oxidative stress leads to the accelerated formation of advanced glycation end products (AGEs), a complex mixture of crosslinked proteins and protein modifications. Relatively high levels of AGEs are generated in diabetes, obesity, AD, and other I neurological diseases. AGEs such as N[e]-carboxymethyllysine (CML) serve as markers for disease progression. AGEs, through interaction with receptors for advanced glycation end products (RAGE), initiate a cascade of deleterious signaling events to form inflammatory cytokines, and thereby further exacerbate oxidative stress in a vicious cycle. AGE inhibitors, AGE breakers, and RAGE inhibitors are therefore potential therapeutic agents for multiple diseases, including diabetes and AD. The complexity of the AGEs and the lack of well-established mechanisms for AGE formation are largely responsible for the lack of effective therapeutics targeting oxidative stress and AGE-related diseases. This review addresses the role of oxidative stress in the pathogenesis of AGE-related chronic diseases, including diabetes and neurological disorders, and recent progress in the development of therapeutics based on antioxidants, AGE breakers and RAGE inhibitors. Furthermore, this review outlines therapeutic strategies based on single-atom nanozymes that attenuate oxidative stress through the sequestering of reactive oxygen species (ROS) and reactive nitrogen species (RNS).}, } @article {pmid38001861, year = {2023}, author = {Fu, RH}, title = {Pectolinarigenin Improves Oxidative Stress and Apoptosis in Mouse NSC-34 Motor Neuron Cell Lines Induced by C9-ALS-Associated Proline-Arginine Dipeptide Repeat Proteins by Enhancing Mitochondrial Fusion Mediated via the SIRT3/OPA1 Axis.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {12}, number = {11}, pages = {}, pmid = {38001861}, issn = {2076-3921}, support = {MOST 105-2314-B-039-017-MY3//The Ministry of Science and Technology (Taiwan)/ ; DMR112-122//China Medical University Hospital (Taiwan)/ ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is considered a fatal progressive degeneration of motor neurons (MN) caused by oxidative stress and mitochondrial dysfunction. There are currently no treatments available. The most common inherited form of ALS is the C9orf72 mutation (C9-ALS). The proline-arginine dipeptide repeat protein (PR-DPR) produced by C9-ALS has been confirmed to be a functionally acquired pathogenic factor that can cause increased ROS, mitochondrial defects, and apoptosis in motor neurons. Pectolinarigenin (PLG) from the traditional medicinal herb Linaria vulgaris has antioxidant and anti-apoptotic properties. I established a mouse NSC-34 motor neuron cell line model expressing PR-DPR and confirmed the neuroprotective effect of PLG. The results showed that ROS production and apoptosis caused by PR-DPR could be improved by PLG treatment. In terms of mechanism research, PR-DPR inhibited the activity of the mitochondrial fusion proteins OPA1 and mitofusin 2. Conversely, the expression of fission protein fission 1 and dynamin-related protein 1 (DRP1) increased. However, PLG treatment reversed these effects. Furthermore, I found that PLG increased the expression and deacetylation of OPA1. Deacetylation of OPA1 enhances mitochondrial fusion and resistance to apoptosis. Finally, transfection with Sirt3 small interfering RNA abolished the neuroprotective effects of PLG. In summary, the mechanism by which PLG alleviates PR-DPR toxicity is mainly achieved by activating the SIRT3/OPA1 axis to regulate the balance of mitochondrial dynamics. Taken together, the potential of PLG in preclinical studies for C9-ALS drug development deserves further evaluation.}, } @article {pmid38001860, year = {2023}, author = {Martinez, A and Lamaizon, CM and Valls, C and Llambi, F and Leal, N and Fitzgerald, P and Guy, C and Kamiński, MM and Inestrosa, NC and van Zundert, B and Cancino, GI and Dulcey, AE and Zanlungo, S and Marugan, JJ and Hetz, C and Green, DR and Alvarez, AR}, title = {c-Abl Phosphorylates MFN2 to Regulate Mitochondrial Morphology in Cells under Endoplasmic Reticulum and Oxidative Stress, Impacting Cell Survival and Neurodegeneration.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {12}, number = {11}, pages = {}, pmid = {38001860}, issn = {2076-3921}, support = {R35 CA231620/CA/NCI NIH HHS/United States ; R35CA23160/BC/NCI NIH HHS/United States ; Intramural funding/TR/NCATS NIH HHS/United States ; }, abstract = {The endoplasmic reticulum is a subcellular organelle key in the control of synthesis, folding, and sorting of proteins. Under endoplasmic reticulum stress, an adaptative unfolded protein response is activated; however, if this activation is prolonged, cells can undergo cell death, in part due to oxidative stress and mitochondrial fragmentation. Here, we report that endoplasmic reticulum stress activates c-Abl tyrosine kinase, inducing its translocation to mitochondria. We found that endoplasmic reticulum stress-activated c-Abl interacts with and phosphorylates the mitochondrial fusion protein MFN2, resulting in mitochondrial fragmentation and apoptosis. Moreover, the pharmacological or genetic inhibition of c-Abl prevents MFN2 phosphorylation, mitochondrial fragmentation, and apoptosis in cells under endoplasmic reticulum stress. Finally, in the amyotrophic lateral sclerosis mouse model, where endoplasmic reticulum and oxidative stress has been linked to neuronal cell death, we demonstrated that the administration of c-Abl inhibitor neurotinib delays the onset of symptoms. Our results uncovered a function of c-Abl in the crosstalk between endoplasmic reticulum stress and mitochondrial dynamics via MFN2 phosphorylation.}, } @article {pmid38001563, year = {2023}, author = {Fröhlich, A and Pfaff, AL and Bubb, VJ and Quinn, JP and Koks, S}, title = {Transcriptomic profiling of cerebrospinal fluid identifies ALS pathway enrichment and RNA biomarkers in MND individuals.}, journal = {Experimental biology and medicine (Maywood, N.J.)}, volume = {248}, number = {23}, pages = {2325-2331}, pmid = {38001563}, issn = {1535-3699}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/complications/metabolism ; *Motor Neuron Disease/cerebrospinal fluid/complications ; Gene Expression Profiling ; Biomarkers/metabolism ; RNA ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder and the most common form of motor neurone disease (MND) which is characterized by the damage and death of motor neurons in the brain and spinal cord of affected individuals. Due to the heterogeneity of the disease, a better understanding of the interaction between genetics and biochemistry with the identification of biomarkers is crucial for therapy development. In this study, we used cerebrospinal fluid (CSF) RNA-sequencing data from the New York Genome Center (NYGC) ALS Consortium and analyzed differential gene expression between 47 MND individuals and 29 healthy controls. Pathway analysis showed that the affected genes are enriched in many pathways associated with ALS, including nucleocytoplasmic transport, autophagy, and apoptosis. Moreover, we assessed differential expression on both gene- and transcript-based levels and demonstrate that the expression of previously identified potential biomarkers, including CAPG, CCL3, and MAP2, was significantly higher in MND individuals. Ultimately, this study highlights the transcriptomic composition of CSF which enables insights into changes in the brain in ALS and therefore increases the confidence in the use of CSF for biomarker development.}, } @article {pmid38001557, year = {2024}, author = {Genge, A and Wainwright, S and Vande Velde, C}, title = {Amyotrophic lateral sclerosis: exploring pathophysiology in the context of treatment.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {25}, number = {3-4}, pages = {225-236}, doi = {10.1080/21678421.2023.2278503}, pmid = {38001557}, issn = {2167-9223}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy/metabolism ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a complex, neurodegenerative disorder in which alterations in structural, physiological, and metabolic parameters act synergistically. Over the last decade there has been a considerable focus on developing drugs to slow the progression of the disease. Despite this, only four disease-modifying therapies are approved in North America. Although additional research is required for a thorough understanding of ALS, we have accumulated a large amount of knowledge that could be better integrated into future clinical trials to accelerate drug development and provide patients with improved treatment options. It is likely that future, successful ALS treatments will take a multi-pronged therapeutic approach, targeting different pathways, akin to personalized medicine in oncology. In this review, we discuss the link between ALS pathophysiology and treatments, looking at the therapeutic failures as learning opportunities that can help us refine and optimize drug development.}, } @article {pmid38001260, year = {2023}, author = {Kuan, LH and Parnianpour, P and Kushol, R and Kumar, N and Anand, T and Kalra, S and Greiner, R}, title = {Accurate personalized survival prediction for amyotrophic lateral sclerosis patients.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {20713}, pmid = {38001260}, issn = {2045-2322}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis ; *Neurodegenerative Diseases ; Probability ; Brain ; Learning ; Disease Progression ; }, abstract = {Amyotrophic Lateral Sclerosis (ALS) is a rapidly progressive neurodegenerative disease. Accurately predicting the survival time for ALS patients can help patients and clinicians to plan for future treatment and care. We describe the application of a machine-learned tool that incorporates clinical features and cortical thickness from brain magnetic resonance (MR) images to estimate the time until a composite respiratory failure event for ALS patients, and presents the prediction as individual survival distributions (ISDs). These ISDs provide the probability of survival (none of the respiratory failures) at multiple future time points, for each individual patient. Our learner considers several survival prediction models, and selects the best model to provide predictions. We evaluate our learned model using the mean absolute error margin (MAE-margin), a modified version of mean absolute error that handles data with censored outcomes. We show that our tool can provide helpful information for patients and clinicians in planning future treatment.}, } @article {pmid38000932, year = {2024}, author = {Abel, EJ and Master, VA and Spiess, PE and Raman, JD and Shapiro, DD and Sexton, WJ and Zemp, L and Patil, D and Lauer, K and Allen, GO and Matin, SF and Karam, JA}, title = {Reply to Eduard Roussel, Riccardo Bertolo, Chiara Ciccarese, et al's Letter to the Editor re: E. Jason Abel, Viraj A. Master, Philippe E. Spiess, et al. The Selection for Cytoreductive Nephrectomy (SCREEN) Score: Improving Surgical Risk Stratification by Integrating Common Radiographic Features. Eur Urol Oncol. 2023;6:266-274.}, journal = {European urology oncology}, volume = {7}, number = {2}, pages = {302-303}, doi = {10.1016/j.euo.2023.10.025}, pmid = {38000932}, issn = {2588-9311}, mesh = {Humans ; *Cytoreduction Surgical Procedures ; *Kidney Neoplasms/surgery ; Nephrectomy ; Risk Assessment ; }, } @article {pmid37999738, year = {2024}, author = {Ovsepian, SV and O'Leary, VB and Martinez, S}, title = {Selective vulnerability of motor neuron types and functional groups to degeneration in amyotrophic lateral sclerosis: review of the neurobiological mechanisms and functional correlates.}, journal = {Brain structure & function}, volume = {229}, number = {1}, pages = {1-14}, pmid = {37999738}, issn = {1863-2661}, support = {Innovation Fund Award 2022//University of Greenwich/ ; COOPERATIO-207036//VBO, Charles University/ ; SAF2017-83702-R//Una manera de hacer Europa/ ; }, mesh = {Humans ; Animals ; *Amyotrophic Lateral Sclerosis ; Motor Neurons ; Disease Models, Animal ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative condition characterised by a progressive loss of motor neurons controlling voluntary muscle activity. The disease manifests through a variety of motor dysfunctions related to the extent of damage and loss of neurons at different anatomical locations. Despite extensive research, it remains unclear why some motor neurons are especially susceptible to the disease, while others are affected less or even spared. In this article, we review the neurobiological mechanisms, neurochemical profiles, and morpho-functional characteristics of various motor neuron groups and types of motor units implicated in their differential exposure to degeneration. We discuss specific cell-autonomous (intrinsic) and extrinsic factors influencing the vulnerability gradient of motor units and motor neuron types to ALS, with their impact on disease manifestation, course, and prognosis, as revealed in preclinical and clinical studies. We consider the outstanding challenges and emerging opportunities for interpreting the phenotypic and mechanistic variability of the disease to identify targets for clinical interventions.}, } @article {pmid37999522, year = {2023}, author = {Metcalf, JS and Banack, SA and Cox, PA}, title = {Cyanotoxin Analysis of Air Samples from the Great Salt Lake.}, journal = {Toxins}, volume = {15}, number = {11}, pages = {}, pmid = {37999522}, issn = {2072-6651}, mesh = {Humans ; *Lakes/microbiology ; *Cyanobacteria ; Water ; Utah ; Cyanobacteria Toxins ; }, abstract = {The Great Salt Lake in Utah is the largest saline lake in the Western hemisphere and one of the largest terminal lakes in the world. Situated at the eastern edge of the Great Basin, it is a remnant of the freshwater Lake Bonneville whose water level precipitously lowered about 12,000 years ago due to a natural break in Red Rock pass to the north. It contains a diverse assemblage of cyanobacteria which vary spatially dependent on salinity. In 1984, the waters of the Great Salt Lake occupied 8500 km[2]. Nearly four decades later, the waters occupy 2500 km[2]-a reduction in surface area of 71%. With predominantly westerly winds, there is a potential for the adjacent metropolitan residents to the east to be exposed to airborne cyanobacteria- and cyanotoxin-containing dust. During the summer and fall months of 2022, air and dried sediment samples were collected and assessed for the presence of BMAA which has been identified as a risk factor for ALS. Collection of air samples equivalent to a person breathing for 1 h resulted in BMAA and isomers being found in some air samples, along with their presence in exposed lakebed samples. There was no clear relationship between the presence of these toxins in airborne and adjacent lakebed samples, suggesting that airborne toxins may originate from diffuse rather than point sources. These findings confirm that continued low water levels in the Great Salt Lake may constitute an increasing health hazard for the 2.5 million inhabitants of communities along the Wasatch Front.}, } @article {pmid37999510, year = {2023}, author = {Violi, JP and Pu, L and Pravadali-Cekic, S and Bishop, DP and Phillips, CR and Rodgers, KJ}, title = {Effects of the Toxic Non-Protein Amino Acid β-Methylamino-L-Alanine (BMAA) on Intracellular Amino Acid Levels in Neuroblastoma Cells.}, journal = {Toxins}, volume = {15}, number = {11}, pages = {}, pmid = {37999510}, issn = {2072-6651}, mesh = {Animals ; Humans ; Amino Acids ; *Amino Acids, Diamino/toxicity/metabolism ; Serine/pharmacology ; Neurotoxins/toxicity ; *Neuroblastoma ; }, abstract = {The cyanobacterial non-protein amino acid (AA) β-Methylamino-L-alanine (BMAA) is considered to be a neurotoxin. BMAA caused histopathological changes in brains and spinal cords of primates consistent with some of those seen in early motor neuron disease; however, supplementation with L-serine protected against some of those changes. We examined the impact of BMAA on AA concentrations in human neuroblastoma cells in vitro. Cells were treated with 1000 µM BMAA and intracellular free AA concentrations in treated and control cells were compared at six time-points over a 48 h culture period. BMAA had a profound effect on intracellular AA levels at specific time points but in most cases, AA homeostasis was re-established in the cell. The most heavily impacted amino acid was serine which was depleted in BMAA-treated cells from 9 h onwards. Correction of serine depletion could be a factor in the observation that supplementation with L-serine protects against BMAA toxicity in vitro and in vivo. AAs that could potentially be involved in protection against BMAA-induced oxidation such as histidine, tyrosine, and phenylalanine were depleted in cells at later time points.}, } @article {pmid37999501, year = {2023}, author = {Metcalf, JS and Banack, SA and Wyatt, PB and Nunn, PB and Cox, PA}, title = {A Direct Analysis of β-N-methylamino-l-alanine Enantiomers and Isomers and Its Application to Cyanobacteria and Marine Mollusks.}, journal = {Toxins}, volume = {15}, number = {11}, pages = {}, pmid = {37999501}, issn = {2072-6651}, mesh = {Animals ; Humans ; Chromatography, Liquid/methods ; Tandem Mass Spectrometry ; *Amino Acids, Diamino/toxicity ; Amino Acids/analysis ; *Bivalvia/chemistry ; *Cyanobacteria/metabolism ; Neurotoxins/toxicity ; }, abstract = {Of the wide variety of toxic compounds produced by cyanobacteria, the neurotoxic amino acid β-N-methylamino-l-alanine (BMAA) has attracted attention as a result of its association with chronic human neurodegenerative diseases such as ALS and Alzheimer's. Consequently, specific detection methods are required to assess the presence of BMAA and its isomers in environmental and clinical materials, including cyanobacteria and mollusks. Although the separation of isomers such as β-amino-N-methylalanine (BAMA), N-(2-aminoethyl)glycine (AEG) and 2,4-diaminobutyric acid (DAB) from BMAA has been demonstrated during routine analysis, a further compounding factor is the potential presence of enantiomers for some of these isomers. Current analytical methods for BMAA mostly do not discriminate between enantiomers, and the chiral configuration of BMAA in cyanobacteria is still largely unexplored. To understand the potential for the occurrence of D-BMAA in cyanobacteria, a chiral UPLC-MS/MS method was developed to separate BMAA enantiomers and isomers and to determine the enantiomeric configuration of endogenous free BMAA in a marine Lyngbya mat and two mussel reference materials. After extraction, purification and derivatization with N-(4-nitrophenoxycarbonyl)-l-phenylalanine 2-methoxyethyl ester ((S)-NIFE), both L- and D-BMAA were identified as free amino acids in cyanobacterial materials, whereas only L-BMAA was identified in mussel tissues. The finding of D-BMAA in biological environmental materials raises questions concerning the source and role of BMAA enantiomers in neurological disease.}, } @article {pmid37997256, year = {2024}, author = {Barker, MS and Ceslis, A and Argall, R and McCombe, P and Henderson, RD and Robinson, GA}, title = {Verbal and nonverbal fluency in amyotrophic lateral sclerosis.}, journal = {Journal of neuropsychology}, volume = {18}, number = {2}, pages = {265-285}, doi = {10.1111/jnp.12354}, pmid = {37997256}, issn = {1748-6653}, support = {//Brazil Family Program for Neurology/ ; //Motor Neurone Disease Research Institute of Australia/ ; APP1135769//National Health and Medical Research Council/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/psychology/complications ; Male ; Female ; Middle Aged ; Aged ; *Neuropsychological Tests ; *Gestures ; Verbal Behavior/physiology ; Apathy/physiology ; Adult ; Semantics ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a multi-system disorder that commonly affects cognition and behaviour. Verbal fluency impairments are consistently reported in ALS patients, and we aimed to investigate whether this deficit extends beyond the verbal domain. We further aimed to determine whether deficits are underpinned by a primary intrinsic response generation impairment (i.e., a global reduction across tasks), potentially related to apathy, or an inability to maintain responding over time (i.e., a 'drop off' pattern). Twenty-two ALS patients and 21 demographically-matched controls completed verbal and nonverbal fluency tasks (phonemic/semantic word fluency, design fluency, gesture fluency and ideational fluency), requiring the generation of responses over a specified time period. Fluency performance was analysed in terms of the overall number of novel items produced, as well as the number of items produced in the first 'initiation' and the remaining 'maintenance' time periods. ALS patients' overall performance was not globally reduced across tasks. Patients were impaired only on meaningful gesture fluency, which requires the generation of gestures that communicate meaning (e.g., waving). On phonemic fluency, ALS patients showed a 'drop off' pattern of performance, where they had difficulty maintaining responding over time, but this pattern was not evident on the other fluency tasks. Apathy did not appear to be related to fluency performance. The selective meaningful gesture fluency deficit, in the context of preserved meaningless gesture fluency, highlights that the retrieval of action knowledge may be weakened in early ALS.}, } @article {pmid37996528, year = {2024}, author = {López-Erauskin, J and Bravo-Hernandez, M and Presa, M and Baughn, MW and Melamed, Z and Beccari, MS and Agra de Almeida Quadros, AR and Arnold-Garcia, O and Zuberi, A and Ling, K and Platoshyn, O and Niño-Jara, E and Ndayambaje, IS and McAlonis-Downes, M and Cabrera, L and Artates, JW and Ryan, J and Hermann, A and Ravits, J and Bennett, CF and Jafar-Nejad, P and Rigo, F and Marsala, M and Lutz, CM and Cleveland, DW and Lagier-Tourenne, C}, title = {Stathmin-2 loss leads to neurofilament-dependent axonal collapse driving motor and sensory denervation.}, journal = {Nature neuroscience}, volume = {27}, number = {1}, pages = {34-47}, pmid = {37996528}, issn = {1546-1726}, support = {RF1 NS124203/NS/NINDS NIH HHS/United States ; R01 NS124203/NS/NINDS NIH HHS/United States ; T32 AG066596/AG/NIA NIH HHS/United States ; P30 NS047101/NS/NINDS NIH HHS/United States ; P30 AG062429/AG/NIA NIH HHS/United States ; T32 GM008666/GM/NIGMS NIH HHS/United States ; R01 NS112503/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Mice ; *Amyotrophic Lateral Sclerosis/metabolism ; Axons/physiology ; Denervation ; DNA-Binding Proteins/genetics ; Intermediate Filaments/metabolism/pathology ; Motor Neurons/metabolism ; Stathmin/genetics/metabolism ; Disease Models, Animal ; }, abstract = {The mRNA transcript of the human STMN2 gene, encoding for stathmin-2 protein (also called SCG10), is profoundly impacted by TAR DNA-binding protein 43 (TDP-43) loss of function. The latter is a hallmark of several neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). Using a combination of approaches, including transient antisense oligonucleotide-mediated suppression, sustained shRNA-induced depletion in aging mice, and germline deletion, we show that stathmin-2 has an important role in the establishment and maintenance of neurofilament-dependent axoplasmic organization that is critical for preserving the caliber and conduction velocity of myelinated large-diameter axons. Persistent stathmin-2 loss in adult mice results in pathologies found in ALS, including reduced interneurofilament spacing, axonal caliber collapse that drives tearing within outer myelin layers, diminished conduction velocity, progressive motor and sensory deficits, and muscle denervation. These findings reinforce restoration of stathmin-2 as an attractive therapeutic approach for ALS and other TDP-43-dependent neurodegenerative diseases.}, } @article {pmid37996229, year = {2023}, author = {Del Pozo Vegas, C and Zalama-Sánchez, D and Sanz-Garcia, A and López-Izquierdo, R and Sáez-Belloso, S and Mazas Perez Oleaga, C and Domínguez Azpíroz, I and Elío Pascual, I and Martín-Rodríguez, F}, title = {Prehospital acute life-threatening cardiovascular disease in elderly: an observational, prospective, multicentre, ambulance-based cohort study.}, journal = {BMJ open}, volume = {13}, number = {11}, pages = {e078815}, pmid = {37996229}, issn = {2044-6055}, mesh = {Adult ; Aged ; Humans ; Ambulances ; *Cardiovascular Diseases/therapy ; Cohort Studies ; *Emergency Medical Services/methods ; Prospective Studies ; }, abstract = {OBJECTIVE: The aim was to explore the association of demographic and prehospital parameters with short-term and long-term mortality in acute life-threatening cardiovascular disease by using a hazard model, focusing on elderly individuals, by comparing patients under 75 years versus patients over 75 years of age.

DESIGN: Prospective, multicentre, observational study.

SETTING: Emergency medical services (EMS) delivery study gathering data from two back-to-back studies between 1 October 2019 and 30 November 2021. Six advanced life support (ALS), 43 basic life support and five hospitals in Spain were considered.

PARTICIPANTS: Adult patients suffering from acute life-threatening cardiovascular disease attended by the EMS.

The primary outcome was in-hospital mortality from any cause within the first to the 365 days following EMS attendance. The main measures included prehospital demographics, biochemical variables, prehospital ALS techniques used and syndromic suspected conditions.

RESULTS: A total of 1744 patients fulfilled the inclusion criteria. The 365-day cumulative mortality in the elderly amounted to 26.1% (229 cases) versus 11.6% (11.6%) in patients under 75 years old. Elderly patients (≥75 years) presented a twofold risk of mortality compared with patients ≤74 years. Life-threatening interventions (mechanical ventilation, cardioversion and defibrillation) were also related to a twofold increased risk of mortality. Importantly, patients suffering from acute heart failure presented a more than twofold increased risk of mortality.

CONCLUSIONS: This study revealed the prehospital variables associated with the long-term mortality of patients suffering from acute cardiovascular disease. Our results provide important insights for the development of specific codes or scores for cardiovascular diseases to facilitate the risk of mortality characterisation.}, } @article {pmid37995198, year = {2023}, author = {Ayoubi, R and Ryan, J and Biddle, MS and Alshafie, W and Fotouhi, M and Bolivar, SG and Ruiz Moleon, V and Eckmann, P and Worrall, D and McDowell, I and Southern, K and Reintsch, W and Durcan, TM and Brown, C and Bandrowski, A and Virk, H and Edwards, AM and McPherson, P and Laflamme, C}, title = {Scaling of an antibody validation procedure enables quantification of antibody performance in major research applications.}, journal = {eLife}, volume = {12}, number = {}, pages = {}, pmid = {37995198}, issn = {2050-084X}, support = {U54 AG065187/AG/NIA NIH HHS/United States ; RF1AG057443/AG/NIA NIH HHS/United States ; R24 GM144308/GM/NIGMS NIH HHS/United States ; FDN154305/CAPMC/CIHR/Canada ; SGC/JAN18/988-797/MNDA_/Motor Neurone Disease Association/United Kingdom ; RF1 AG057443/AG/NIA NIH HHS/United States ; U54AG065187/AG/NIA NIH HHS/United States ; }, mesh = {Humans ; *Proteome ; *Antibodies/chemistry ; }, abstract = {Antibodies are critical reagents to detect and characterize proteins. It is commonly understood that many commercial antibodies do not recognize their intended targets, but information on the scope of the problem remains largely anecdotal, and as such, feasibility of the goal of at least one potent and specific antibody targeting each protein in a proteome cannot be assessed. Focusing on antibodies for human proteins, we have scaled a standardized characterization approach using parental and knockout cell lines (Laflamme et al., 2019) to assess the performance of 614 commercial antibodies for 65 neuroscience-related proteins. Side-by-side comparisons of all antibodies against each target, obtained from multiple commercial partners, have demonstrated that: (i) more than 50% of all antibodies failed in one or more applications, (ii) yet, ~50-75% of the protein set was covered by at least one high-performing antibody, depending on application, suggesting that coverage of human proteins by commercial antibodies is significant; and (iii) recombinant antibodies performed better than monoclonal or polyclonal antibodies. The hundreds of underperforming antibodies identified in this study were found to have been used in a large number of published articles, which should raise alarm. Encouragingly, more than half of the underperforming commercial antibodies were reassessed by the manufacturers, and many had alterations to their recommended usage or were removed from the market. This first study helps demonstrate the scale of the antibody specificity problem but also suggests an efficient strategy toward achieving coverage of the human proteome; mine the existing commercial antibody repertoire, and use the data to focus new renewable antibody generation efforts.}, } @article {pmid37993492, year = {2023}, author = {Ragagnin, AMG and Sundaramoorthy, V and Farzana, F and Gautam, S and Saravanabavan, S and Takalloo, Z and Mehta, P and Do-Ha, D and Parakh, S and Shadfar, S and Hunter, J and Vidal, M and Jagaraj, CJ and Brocardo, M and Konopka, A and Yang, S and Rayner, SL and Williams, KL and Blair, IP and Chung, RS and Lee, A and Ooi, L and Atkin, JD}, title = {ALS/FTD-associated mutation in cyclin F inhibits ER-Golgi trafficking, inducing ER stress, ERAD and Golgi fragmentation.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {20467}, pmid = {37993492}, issn = {2045-2322}, support = {10305133//National Health and Medical Research Council of Australia (NHMRC)/ ; 1086887//National Health and Medical Research Council of Australia (NHMRC)/ ; 1095215//National Health and Medical Research Council of Australia (NHMRC)/ ; 10305133//National Health and Medical Research Council of Australia (NHMRC)/ ; 1086887//National Health and Medical Research Council of Australia (NHMRC)/ ; 1095215//National Health and Medical Research Council of Australia (NHMRC)/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism ; *Frontotemporal Dementia/genetics/metabolism ; Endoplasmic Reticulum-Associated Degradation ; Endoplasmic Reticulum/metabolism ; Golgi Apparatus/metabolism ; Mutation ; Cyclins/metabolism ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a severely debilitating neurodegenerative condition that is part of the same disease spectrum as frontotemporal dementia (FTD). Mutations in the CCNF gene, encoding cyclin F, are present in both sporadic and familial ALS and FTD. However, the pathophysiological mechanisms underlying neurodegeneration remain unclear. Proper functioning of the endoplasmic reticulum (ER) and Golgi apparatus compartments is essential for normal physiological activities and to maintain cellular viability. Here, we demonstrate that ALS/FTD-associated variant cyclin F[S621G] inhibits secretory protein transport from the ER to Golgi apparatus, by a mechanism involving dysregulation of COPII vesicles at ER exit sites. Consistent with this finding, cyclin F[S621G] also induces fragmentation of the Golgi apparatus and activates ER stress, ER-associated degradation, and apoptosis. Induction of Golgi fragmentation and ER stress were confirmed with a second ALS/FTD variant cyclin F[S195R], and in cortical primary neurons. Hence, this study provides novel insights into pathogenic mechanisms associated with ALS/FTD-variant cyclin F, involving perturbations to both secretory protein trafficking and ER-Golgi homeostasis.}, } @article {pmid37993052, year = {2024}, author = {Wu, F and Malek, AM and Buchanich, JM and Arena, VC and Rager, JR and Sharma, RK and Vena, JE and Bear, T and Talbott, EO}, title = {Exposure to ambient air toxicants and the risk of amyotrophic lateral sclerosis (ALS): A matched case control study.}, journal = {Environmental research}, volume = {242}, number = {}, pages = {117719}, doi = {10.1016/j.envres.2023.117719}, pmid = {37993052}, issn = {1096-0953}, support = {R01 TS000272/TS/ATSDR CDC HHS/United States ; }, mesh = {Humans ; United States/epidemiology ; Case-Control Studies ; *Amyotrophic Lateral Sclerosis/chemically induced/epidemiology ; *Vinyl Chloride ; Bayes Theorem ; Risk Factors ; Solvents ; Cyanides ; *Dinitrobenzenes ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder with few risk factors identified and no known cure. Gene-environment interaction is hypothesized especially for sporadic ALS cases (90-95%) which are of unknown etiology. We aimed to investigate risk factors for ALS including exposure to ambient air toxics.

METHODS: This population-based case-control study included 267 ALS cases (from the United States [U.S.] Centers for Disease Control and Prevention/Agency for Toxic Substances and Disease Registry National ALS Registry and Biorepository) and 267 age, sex, and county-matched controls identified via a commercial database. Exposure assessment for 34 ambient air toxicants was performed by assigning census tract-level U.S. Environmental Protection Agency (EPA) 2011 National Air Toxics Assessment (NATA) data to participants' residential ZIP codes. Conditional logistic regression was used to compute adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for individual compounds, chemical classes, and overall exposure. Sensitivity analyses using both conditional logistic regression and Bayesian grouped weighted quartile sum (GWQS) models were performed to assess the integrity of findings.

RESULTS: Using the 2011 NATA, the highest exposure quartile (Q4) compared to the lowest (Q1) of vinyl chloride (aOR = 6.00, 95% CI: 1.87-19.25), 2,4-dinitrotoluene (aOR = 5.45, 95% CI: 1.53-19.36), cyanide (aOR = 4.34, 95% CI: 1.52-12.43), cadmium (aOR = 3.30, 95% CI: 1.11-9.77), and carbon disulfide (aOR = 2.98, 95% CI: 1.00-8.91) was associated with increased odds of ALS. Residential air selenium showed an inverse association with ALS (second quartile [Q2] vs. Q1: aOR = 0.38, 95% CI: 0.18-0.79). Additionally, residential exposure to organic/chlorinated solvents (Q4 vs Q1: aOR = 2.62, 95% CI: 1.003-6.85) was associated with ALS.

CONCLUSIONS: Our findings using the 2011 NATA linked by census tract to residential area provide evidence of increased ALS risk in cases compared to controls for 2,4-dinitrotoluene, vinyl chloride, cyanide, and the organic/chlorinated solvents class. This underscores the importance of ongoing surveillance of potential exposures for at-risk populations.}, } @article {pmid37992921, year = {2024}, author = {Li, L and Lei, T and Xing, C and Du, H}, title = {Advances in microfluidic chips targeting toxic aggregation proteins for neurodegenerative diseases.}, journal = {International journal of biological macromolecules}, volume = {256}, number = {Pt 2}, pages = {128308}, doi = {10.1016/j.ijbiomac.2023.128308}, pmid = {37992921}, issn = {1879-0003}, mesh = {Humans ; *Neurodegenerative Diseases/metabolism ; Microfluidics ; *Alzheimer Disease ; Amyloid beta-Peptides ; }, abstract = {Neurodegenerative diseases (NDs) are characterized by nervous system damage, often influenced by genetic and aging factors. Pathological analysis frequently reveals the presence of aggregated toxic proteins. The intricate and poorly understood origins of these diseases have hindered progress in early diagnosis and drug development. The development of novel in-vitro and in-vivo models could enhance our comprehension of ND mechanisms and facilitate clinical treatment advancements. Microfluidic chips are employed to establish three-dimensional culture conditions, replicating the human ecological niche and creating a microenvironment conducive to neuronal cell survival. The incorporation of mechatronic controls unifies the chip, cells, and culture medium optimizing living conditions for the cells. This study provides a comprehensive overview of microfluidic chip applications in drug and biomarker screening for neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, Huntington's disease, multiple sclerosis, and amyotrophic lateral sclerosis. Our Lab-on-a-Chip system releases toxic proteins to simulate the pathological characteristics of neurodegenerative diseases, encompassing β-amyloid, α-synuclein, huntingtin, TAR DNA-binding protein 43, and Myelin Basic Protein. Investigating molecular and cellular interactions in vitro can enhance our understanding of disease mechanisms while minimizing harmful protein levels and can aid in screening potential therapeutic agents. We anticipate that our research will promote the utilization of microfluidic chips in both fundamental research and clinical applications for neurodegenerative diseases.}, } @article {pmid37992159, year = {2023}, author = {Shimizu, M and Shiraishi, N and Tada, S and Sasaki, T and Beck, G and Nagano, S and Kinoshita, M and Sumi, H and Sugimoto, T and Ishida, Y and Koda, T and Ishikura, T and Sugiyama, Y and Kihara, K and Kanakura, M and Nakajima, T and Takeda, S and Takahashi, MP and Yamashita, T and Okuno, T and Mochizuki, H}, title = {RGMa collapses the neuronal actin barrier against disease-implicated protein and exacerbates ALS.}, journal = {Science advances}, volume = {9}, number = {47}, pages = {eadg3193}, pmid = {37992159}, issn = {2375-2548}, mesh = {Animals ; Humans ; Mice ; Actins ; *Amyotrophic Lateral Sclerosis/genetics/pathology ; Antibodies ; Mice, Transgenic ; Motor Neurons/metabolism ; Superoxide Dismutase/genetics/metabolism ; Superoxide Dismutase-1/genetics ; }, abstract = {Repulsive guidance molecule A (RGMa) was originally identified as a neuronal growth cone-collapsing factor. Previous reports have demonstrated the multifunctional roles of RGMa mediated by neogenin1. However, the pathogenic involvement of RGMa in amyotrophic lateral sclerosis (ALS) remains unclear. Here, we demonstrated that RGMa concentration was elevated in the cerebrospinal fluid of both patients with ALS and transgenic mice overexpressing the mutant human superoxide dismutase1 (mSOD1 mice). Treatment with humanized anti-RGMa monoclonal antibody ameliorated the clinical symptoms in mSOD1 mice. Histochemical analysis revealed that the anti-RGMa antibody significantly decreased mutant SOD1 protein accumulation in the motor neurons of mSOD1 mice via inhibition of actin depolymerization. In vitro analysis revealed that the anti-RGMa antibody inhibited the cellular uptake of the mutant SOD1 protein, presumably by reinforcing the neuronal actin barrier. Collectively, these data suggest that RGMa leads to the collapse of the neuronal actin barrier and promotes aberrant protein deposition, resulting in exacerbation of the ALS pathology.}, } @article {pmid37991691, year = {2024}, author = {Yu, L and Xu, G and Zhou, Q and Ouyang, M and Gao, L and Zeng, S}, title = {Biomechanical properties of the ascending aorta in patients with arterial hypertension by velocity vector imaging.}, journal = {The international journal of cardiovascular imaging}, volume = {40}, number = {2}, pages = {397-405}, pmid = {37991691}, issn = {1875-8312}, support = {81801721//the State Natural Sciences Foundation of China/ ; 81871372//the State Natural Sciences Foundation of China/ ; 2019JJ50880//the Natural Science Foundation of Hunan Province/ ; 2019JJ40425//the Natural Science Foundation of Hunan Province/ ; }, mesh = {Humans ; Aorta, Thoracic ; Predictive Value of Tests ; *Hypertension/complications/diagnosis/epidemiology ; Aorta/diagnostic imaging ; Echocardiography/methods ; *Aortic Diseases ; *Ventricular Dysfunction, Left ; }, abstract = {Aortic stiffness is an important risk factor for cardiovascular events and morbidity. Increased aortic stiffness is associated with an increase in cardiac and vascular hypertension-related organ damage. To evaluate the biomechanical properties of the ascending aorta (AA) in patients with arterial hypertension (AH) by velocity vector imaging (VVI). Ninety-five patients with AH and 53 normal healthy control participants were prospectively enrolled. AA biomechanical properties, i.e., ascending aortic global longitudinal strain (ALS), ascending aortic global circumferential strain (ACS), and fractional area change (FAC), were evaluated by VVI. Relative wall thickness (RWT) and left ventricular mass (LVM) were calculated. Pulsed Doppler early transmitral peak flow velocity (E), early diastolic mitral annular velocity (e'), left ventricular global longitudinal strain (GLS), distensibility (D) and stiffness index (SI) of AA were also obtained. The ALS, ACS and FAC were significantly lower in the AH patients, especially in those with ascending aorta dilatation (AAD), than in the normal healthy control subjects. The patients with AAD had a higher E/e' ratio, RWT, LVM and SI and a lower GLS and D than patients without AAD and normal healthy volunteers (p < 0.05). There were significant associations between biomechanical properties and D, SI, E/e' and GLS (ALS and D: r = 0.606, ALS and SI: r = - 0.645, ALS and E/e': r = - 0.489, ALS and GLS: r = 0.466, ACS and D: r = 0.564, ACS and SI: r = - 0.567, ACS and E/e': r = - 0.313, ACS and GLS: r = 0.320, FAC and D: r = 0.649, FAC and SI: r = - 0.601, FAC and E/e': r = - 0.504, FAC and GLS: r = 0.524, respectively, p < 0.05). The biomechanical properties of AA were impaired in patients with AH, especially patients with ascending aorta dilatation. Hypertension is associated with a high prevalence of diastolic and systolic dysfunction and increased arterial stiffness. Further study is needed to evaluate the clinical application of AA biomechanical properties by VVI.}, } @article {pmid37990637, year = {2024}, author = {Ng, SC and McCombie, A and Frizelle, F and Eglinton, T}, title = {Influence of the type of anatomic resection on anastomotic leak after surgery for colon cancer.}, journal = {ANZ journal of surgery}, volume = {94}, number = {3}, pages = {424-428}, doi = {10.1111/ans.18782}, pmid = {37990637}, issn = {1445-2197}, mesh = {Humans ; Male ; *Anastomotic Leak/epidemiology/etiology ; Retrospective Studies ; Risk Factors ; *Colonic Neoplasms/pathology ; Colectomy/adverse effects/methods ; Anastomosis, Surgical/adverse effects/methods ; }, abstract = {INTRODUCTION: Anastomotic leak (AL) after colon cancer resection is feared by surgeons because of its associated morbidity and mortality. Considerable research has been directed at predictive factors for AL, but not the anatomic type of colonic resection. Anecdotally, certain types of resection are associated with higher leak rates although there remains a paucity of data on this. This study aimed to determine the AL rate for different types of colon cancer resection to inform decisions regarding the choice of operation.

METHODOLOGY: Retrospective analysis of Bowel Cancer Outcome Registry (BCOR) for all colonic cancer resections with anastomosis between January 2007 and December 2020. Demographic, patient, tumour and outcome data were analysed. AL rates were compared among the different colonic procedures with both univariate and multivariate analysis.

RESULTS: 20 191 patients who underwent resection with anastomosis for cancer were included in this study. Of these 535 (2.6%) suffered ALs. While the univariate analysis found male sex, procedure type, symptomatic cancers, emergency surgery, unsupervised registrars, conversion to open surgery, medical complications and higher TNM staging were associated with AL, multivariate analysis, found only procedure type remained a significant predictor of AL (total colectomy (OR 4.049, P<0.001), subtotal colectomy (OR 2.477, P<0.001) and extended right hemicolectomy (OR 2.171, P < 0.001)).

CONCLUSION: AL is more common in extended colonic resections. With growing evidence of similar oncological outcomes between subtotal colectomy and left hemicolectomy for splenic flexure cancers, more limited resections should be considered. The type of colonic resection should be integrated into prediction tools for AL.}, } @article {pmid37988788, year = {2024}, author = {Basith, S and Manavalan, B and Lee, G}, title = {Unveiling local and global conformational changes and allosteric communications in SOD1 systems using molecular dynamics simulation and network analyses.}, journal = {Computers in biology and medicine}, volume = {168}, number = {}, pages = {107688}, doi = {10.1016/j.compbiomed.2023.107688}, pmid = {37988788}, issn = {1879-0534}, mesh = {Humans ; Superoxide Dismutase-1/genetics/metabolism ; *Molecular Dynamics Simulation ; Superoxide Dismutase/chemistry/genetics/metabolism ; *Amyotrophic Lateral Sclerosis/genetics ; Mutation ; Protein Folding ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a serious neurodegenerative disorder affecting nerve cells in the brain and spinal cord that is caused by mutations in the superoxide dismutase 1 (SOD1) enzyme. ALS-related mutations cause misfolding, dimerisation instability, and increased formation of aggregates. The underlying allosteric mechanisms, however, remain obscure as far as details of their fundamental atomistic structure are concerned. Hence, this gap in knowledge limits the development of novel SOD1 inhibitors and the understanding of how disease-associated mutations in distal sites affect enzyme activity.

METHODS: We combined microsecond-scale based unbiased molecular dynamics (MD) simulation with network analysis to elucidate the local and global conformational changes and allosteric communications in SOD1 Apo (unmetallated form), Holo, Apo_CallA (mutant and unmetallated form), and Holo_CallA (mutant form) systems. To identify hotspot residues involved in SOD1 signalling and allosteric communications, we performed network centrality, community network, and path analyses.

RESULTS: Structural analyses showed that unmetallated SOD1 systems and cysteine mutations displayed large structural variations in the catalytic sites, affecting structural stability. Inter- and intra H-bond analyses identified several important residues crucial for maintaining interfacial stability, structural stability, and enzyme catalysis. Dynamic motion analysis demonstrated more balanced atomic displacement and highly correlated motions in the Holo system. The rationale for structural disparity observed in the disulfide bond formation and R143 configuration in Apo and Holo systems were elucidated using distance and dihedral probability distribution analyses.

CONCLUSION: Our study highlights the efficiency of combining extensive MD simulations with network analyses to unravel the features of protein allostery.}, } @article {pmid37988653, year = {2024}, author = {Teplansky, KJ and Wisler, A and Goffman, L and Wang, J}, title = {The Impact of Stimulus Length in Tongue and Lip Movement Pattern Stability in Amyotrophic Lateral Sclerosis.}, journal = {Journal of speech, language, and hearing research : JSLHR}, volume = {67}, number = {10S}, pages = {4002-4014}, pmid = {37988653}, issn = {1558-9102}, support = {R01 DC013547/DC/NIDCD NIH HHS/United States ; R01 DC016621/DC/NIDCD NIH HHS/United States ; R03 DC013990/DC/NIDCD NIH HHS/United States ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology ; *Lip/physiopathology/physiology ; *Tongue/physiopathology/physiology ; Male ; Female ; Middle Aged ; Aged ; *Movement/physiology ; Speech/physiology ; Adult ; Speech Production Measurement ; Biomechanical Phenomena ; Case-Control Studies ; }, abstract = {PURPOSE: This study aimed to investigate the effect of stimulus signal length on tongue and lip motion pattern stability in speakers diagnosed with amyotrophic lateral sclerosis (ALS) compared to healthy controls.

METHOD: Electromagnetic articulography was used to derive articulatory motion patterns from individuals with mild (n = 27) and severe (n = 16) ALS and healthy controls (n = 25). The spatiotemporal index (STI) was used as a measure of articulatory stability. Two experiments were conducted to evaluate signal length effects on the STI: (a) the effect of the number of syllables on STI values and (b) increasing lengths of subcomponents of a single phrase. Two-way mixed analyses of variance were conducted to assess the effects of syllable length and group on the STI for the tongue tip (TT), tongue back (TB), and lower lip (LL).

RESULTS: Experiment 1 showed a significant main effect of syllable length (TT, p < .001; TB, p < .001; and LL, p < .001) and group (TT, p = .037; TB, p = .007; and LL, p = .017). TB and LL stability was generally higher with speech stimuli that included a greater number of syllables. Articulatory variability was significantly higher in speakers diagnosed with ALS compared to healthy controls. Experiment 2 showed a significant main effect of length (TT, p < .001; TB, p = .015; and LL, p < .001), providing additional support that STI values tend to be greater when calculated on longer speech signals.

CONCLUSIONS: Articulatory stability is influenced by the length of speech signals and manifests similarly in both healthy speakers and persons with ALS. TT stability may be significantly impacted by phonemic content due to greater movement flexibility. Compared to healthy controls, there was an increase in articulatory variability in those with ALS, which likely reflects deviations in speech motor control.

SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.24463924.}, } @article {pmid37988405, year = {2024}, author = {Nusrath, S and Kalluru, P and Shukla, S and Dharanikota, A and Basude, M and Jonnada, P and Abualjadayel, M and Alabbad, S and Mir, TA and Broering, DC and Raju, K and Rao, TS and Vashist, YK}, title = {Current status of indocyanine green fluorescent angiography in assessing perfusion of gastric conduit and oesophago-gastric anastomosis.}, journal = {International journal of surgery (London, England)}, volume = {110}, number = {2}, pages = {1079-1089}, pmid = {37988405}, issn = {1743-9159}, mesh = {Humans ; *Indocyanine Green ; *Coloring Agents ; Angiography/adverse effects ; Anastomotic Leak/diagnostic imaging/etiology ; Anastomosis, Surgical/adverse effects/methods ; Esophagectomy/adverse effects/methods ; Perfusion ; }, abstract = {Anastomotic leak (AL) remains a significant complication after esophagectomy. Indocyanine green fluorescent angiography (ICG-FA) is a promising and safe technique for assessing gastric conduit (GC) perfusion intraoperatively. It provides detailed visualization of tissue perfusion and has demonstrated usefulness in oesophageal surgery. GC perfusion analysis by ICG-FA is crucial in constructing the conduit and selecting the anastomotic site and enables surgeons to make necessary adjustments during surgery to potentially reduce ALs. However, anastomotic integrity involves multiple factors, and ICG-FA must be combined with optimization of patient and procedural factors to decrease AL rates. This review summarizes ICG-FA's current applications in assessing esophago-gastric anastomosis perfusion, including qualitative and quantitative analysis and different imaging systems. It also explores how fluorescent imaging could decrease ALs and aid clinicians in utilizing ICG-FA to improve esophagectomy outcomes.}, } @article {pmid37986827, year = {2023}, author = {Simmonds, E and Levine, KS and Han, J and Iwaki, H and Koretsky, MJ and Kuznetsov, N and Faghri, F and Solsberg, CW and Schuh, A and Jones, L and Bandres-Ciga, S and Blauwendraat, C and Singleton, A and Escott-Price, V and Leonard, HL and Nalls, MA}, title = {Sleep disturbances as risk factors for neurodegeneration later in life.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, pmid = {37986827}, abstract = {The relationship between sleep disorders and neurodegeneration is complex and multi-faceted. Using over one million electronic health records (EHRs) from Wales, UK, and Finland, we mined biobank data to identify the relationships between sleep disorders and the subsequent manifestation of neurodegenerative diseases (NDDs) later in life. We then examined how these sleep disorders' severity impacts neurodegeneration risk. Additionally, we investigated how sleep attributed risk may compensate for the lack of genetic risk factors (i.e. a lower polygenic risk score) in NDD manifestation. We found that sleep disorders such as sleep apnea were associated with the risk of Alzheimer's disease (AD), amyotrophic lateral sclerosis, dementia, Parkinson's disease (PD), and vascular dementia in three national scale biobanks, with hazard ratios (HRs) ranging from 1.31 for PD to 5.11 for dementia. These sleep disorders imparted significant risk up to 15 years before the onset of an NDD. Cumulative number of sleep disorders in the EHRs were associated with a higher risk of neurodegeneration for dementia and vascular dementia. Sleep related risk factors were independent of genetic risk for Alzheimer's and Parkinson's, potentially compensating for low genetic risk in overall disease etiology. There is a significant multiplicative interaction regarding the combined risk of sleep disorders and Parkinson's disease. Poor sleep hygiene and sleep apnea are relatively modifiable risk factors with several treatment options, including CPAP and surgery, that could potentially reduce the risk of neurodegeneration. This is particularly interesting in how sleep related risk factors are significantly and independently enriched in manifesting NDD patients with low levels of genetic risk factors for these diseases.}, } @article {pmid37986813, year = {2023}, author = {Glineburg, MR and Yildirim, E and Gomez, N and Li, X and Pak, J and Altheim, C and Waksmacki, J and McInerney, G and Barmada, SJ and Todd, PK}, title = {Stress granule formation helps to mitigate neurodegeneration.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {37986813}, issn = {2692-8205}, support = {R01 NS086810/NS/NINDS NIH HHS/United States ; P50 HD104463/HD/NICHD NIH HHS/United States ; I01 BX004842/BX/BLRD VA/United States ; R01 NS099280/NS/NINDS NIH HHS/United States ; R01 NS113943/NS/NINDS NIH HHS/United States ; R01 NS097542/NS/NINDS NIH HHS/United States ; R56 NS128110/NS/NINDS NIH HHS/United States ; }, abstract = {Cellular stress pathways that inhibit translation initiation lead to transient formation of cytoplasmic RNA/protein complexes known as stress granules. Many of the proteins found within stress granules and the dynamics of stress granule formation and dissolution are implicated in neurodegenerative disease. Whether stress granule formation is protective or harmful in neurodegenerative conditions is not known. To address this, we took advantage of the alphavirus protein nsP3, which selectively binds dimers of the central stress granule nucleator protein G3BP (rin in Drosophila) and markedly reduces stress granule formation without directly impacting the protein translational inhibitory pathways that trigger stress granule formation. In Drosophila and rodent neurons, reducing stress granule formation with nsP3 had modest impacts on lifespan even in the setting of serial stress pathway induction. In contrast, reducing stress granule formation in models of ataxia, amyotrophic lateral sclerosis and frontotemporal dementia largely exacerbated disease phenotypes. These data support a model whereby stress granules mitigate, rather than promote, neurodegenerative cascades.}, } @article {pmid37986728, year = {2023}, author = {Fan, C and Hahn, N and Kamdar, F and Avansino, D and Wilson, GH and Hochberg, L and Shenoy, KV and Henderson, JM and Willett, FR}, title = {Plug-and-Play Stability for Intracortical Brain-Computer Interfaces: A One-Year Demonstration of Seamless Brain-to-Text Communication.}, journal = {ArXiv}, volume = {}, number = {}, pages = {}, pmid = {37986728}, issn = {2331-8422}, abstract = {Intracortical brain-computer interfaces (iBCIs) have shown promise for restoring rapid communication to people with neurological disorders such as amyotrophic lateral sclerosis (ALS). However, to maintain high performance over time, iBCIs typically need frequent recalibration to combat changes in the neural recordings that accrue over days. This requires iBCI users to stop using the iBCI and engage in supervised data collection, making the iBCI system hard to use. In this paper, we propose a method that enables self-recalibration of communication iBCIs without interrupting the user. Our method leverages large language models (LMs) to automatically correct errors in iBCI outputs. The self-recalibration process uses these corrected outputs ("pseudo-labels") to continually update the iBCI decoder online. Over a period of more than one year (403 days), we evaluated our Continual Online Recalibration with Pseudo-labels (CORP) framework with one clinical trial participant. CORP achieved a stable decoding accuracy of 93.84% in an online handwriting iBCI task, significantly outperforming other baseline methods. Notably, this is the longest-running iBCI stability demonstration involving a human participant. Our results provide the first evidence for long-term stabilization of a plug-and-play, high-performance communication iBCI, addressing a major barrier for the clinical translation of iBCIs.}, } @article {pmid37984338, year = {2023}, author = {Topaloğlu Ören, ED and Dorukoğlu, S and Ertem, G}, title = {The Use of Complementary and Alternative Medicine and Coping with Stress by Patients with Gynecological Cancer: A Cross-Sectional Study in Türkiye.}, journal = {Complementary medicine research}, volume = {30}, number = {6}, pages = {502-516}, doi = {10.1159/000534707}, pmid = {37984338}, issn = {2504-2106}, mesh = {Humans ; Female ; Adult ; Middle Aged ; Aged ; Aged, 80 and over ; Cross-Sectional Studies ; Turkey ; *Neoplasms ; *Complementary Therapies ; Adaptation, Psychological ; }, abstract = {INTRODUCTION: Gynecological cancers are long-term, challenging, and stressful diseases. In Türkiye, the majority of patients with gynecological cancer use complementary and alternative medicine (CAM). Considering the stress that gynecological cancer patients are exposed to, patients need to know how to cope with stress.

OBJECTIVE: This study aimed to determine the use of CAM and coping with stress by patients with gynecological cancer and the relationships between them and the factors that predict the approaches to coping with stress in women with gynecological cancer in Türkiye.

METHODS: This is a descriptive and cross-sectional study. The study was conducted with 204 patients between April and August 2022. The data of the study were collected by face-to-face interview and filled out by the patients using the Descriptive Information Form and the Stress Coping Styles Scale (SCSS). Number, percentage, mean, χ2, one-way ANOVA, t test, and the Spearman correlation analysis were used in the data analysis. To analyze the multivariate independent associations between variables, a multivariate ordinal logistic regression model was used, with the SCSS domains as dependent variables. A 95% confidence interval was calculated, and all statistical tests had an alpha level of 0.05.

RESULTS: The mean age of the patients was 58.38 ± 12.64 years (32-80). The prevalence of CAM use by patients was 39.2%, and the most common types of CAM were herbal products (43.8%) and supplication (42.5%). The reasons for using CAM were relaxation (symptomatic)-feeling healthy (63.8%) and treating cancer (36.2%). No statistically significant difference was found between the use of CAM and their approaches to coping with stress (p > 0.05). As a result of multivariate ordinal logistic regression analysis, education level under high school, having ovary, cervix, and endometrium cancer, being in the first stage of cancer, receiving chemotherapy, receiving surgical treatment, having another cancer patient in the social environment and increased interest in a partner after the diagnosis of cancer was associated with an effective coping with stress (p < 0.05, adjusted R2 = 0.27, 0.79, and 0.32, respectively). Not working, experiencing an abortion, having another cancer patient in their social environment, being in the third stage of cancer, having an extended family, and living in a rural area of residence were associated with ineffective coping with stress (p < 0.05, adjusted R2 = 0.20 and 0.24, respectively).

CONCLUSIONS: The prevalence of CAM use by patients was low. While determining the approaches of the patients to cope with stress, their education level, place of residence, family type, diagnosis of cancer, stage of cancer, treatment, partner support, and stressful life events should be considered. As nurses, we need to be more knowledgeable about the use of CAM to provide correct guidance to our patients for access to accurate and effective information. We need to determine our patients' stressors and how our patients cope with stress.

UNLABELLED: EinleitungGynäkologische Krebserkrankungen sind langfristige, herausfordernde und belastende Krankheiten. In der Türkei nehmen die meisten Patientinnen mit gynäkologischen Krebserkrankungen Komplementär- und Alternativmedizin in Anspruch. Angesichts der großen Belastungen, denen Patientinnen mit gynäkologischen Krebserkrankungen ausgesetzt sind, müssen sie wissen, wie sie mit Stress umgehen können.ZielMit dieser Studie sollen die Inanspruchnahme von Komplementär- und Alternativmedizin und die Stressbewältigung von Patientinnen mit gynäkologischer Krebserkrankung ermittelt werden und es sollen die Zusammenhänge zwischen diesen beiden Aspekten und den prädiktiven Faktoren für die Ansätze zur Stressbewältigung bei Frauen mit gynäkologischer Krebserkrankung untersucht werden.MethodenEs handelt sich um eine deskriptive Querschnittsstudie. Die Studie wurde mit 204 Patientinnen zwischen April und August 2022 durchgeführt. Die Erhebung der Studiendaten erfolgte durch persönliche Befragung und mithilfe des deskriptiven Informationsformulars sowie der Stress Coping Styles-Skala, die die Patientinnen ausfüllten. Für die Datenanalyse wurden Anzahl, Prozentanteil, Mittelwert, Chi-Quadrat-Test, einfaktorielle ANOVA, t Test und die Spearman-Korrelationsanalyse verwendet. Zur Analyse der multivariaten unabhängigen Zusammenhänge zwischen den Variablen wurde ein multivariates ordinales logistisches Regressionsmodell verwendet mit den SCSS (Stress Coping Styles-Skala)-Domänen als abhängigen Variablen. Es wurde ein 95%-Konfidenzintervall berechnet, und das Signifikanzniveau betrug für alle statistischen Tests α = 0.05.ErgebnisseDas Durchschnittsalter der Patientinnen betrug 58.38 ± 12.64 Jahre (32–80 Jahre). Die Prävalenz der Inanspruchnahme von Komplementär- und Alternativmedizin (CAM) durch die Patientinnen lag bei 39.2%, und die häufigsten CAM-Arten waren pflanzliche Produkte (43.8%) und Bittgebete (42.5%). Die Gründe für die Inanspruchnahme von Komplementär- und Alternativmedizin waren Entspannung (symptomatisch), das Gefühl von Gesundheit (63.8%) und die Behandlung der Krebserkrankung (36.2%). Es fand sich kein statistisch signifikanter Unterschied zwischen der Inanspruchnahme von Komplementär- und Alternativmedizin und ihren Ansätzen zur Stressbewältigung (p > 0.05). Die multivariate ordinale logistische Regressionsanalyse zeigte, dass ein Bildungsniveau unterhalb der Oberstufe sowie Ovarial-, Zervix- und Endometriumkarzinom, Krebs im Anfangsstadium, Chemotherapie, operative Behandlung, eine andere Krebspatientin im sozialen Umfeld und ein gesteigertes Interesse an einem Partner nach der Krebsdiagnose mit effektiver Stressbewältigung assoziiert waren (p < 0.05, adjustiertes R2 = 0.27, 0.79 bzw. 0.32). Fehlende Berufstätigkeit, Fehlgeburt/Schwangerschaftsabbruch, eine andere Krebspatientin im sozialen Umfeld, eine Krebserkrankung im dritten Stadium, eine Großfamilie zu haben und in einer ländlichen Gegend zu leben waren mit ineffektiver Stressbewältigung verbunden (p < 0.05, adjustiertes R2 = 0.20 bzw. 0.24).SchlussfolgerungenDie Prävalenz der Inanspruchnahme von Komplementär- und Alternativmedizin durch die Patientinnen war gering. Bei der Ermittlung der Ansätze der Patientinnen zur Stressbewältigung sollten ihr Bildungsniveau, ihr Wohnort, ihr Familientyp, die Krebsdiagnose, das Krebsstadium, die Behandlung, die Unterstützung durch den Partner und belastende Lebensereignisse berücksichtigt werden. Als Pflegekräfte müssen wir mehr über die Inanspruchnahme von Komplementär- und Alternativmedizin wissen, um unsere Patientinnen in Hinblick auf den Zugang zu genauen und wirksamen Informationen die richtige Orientierungshilfe zu geben. Wir müssen die Stressfaktoren unserer Patientinnen ermitteln und herausfinden, wie unsere Patientinnen mit Stress umgehen.}, } @article {pmid37983967, year = {2024}, author = {Slyne, AD and Ó Murchú, SC}, title = {Persistent inward currents: PICking apart the temporal changes in intrinsic motor neuron excitability in amyotrophic lateral sclerosis.}, journal = {The Journal of physiology}, volume = {602}, number = {1}, pages = {13-14}, doi = {10.1113/JP285776}, pmid = {37983967}, issn = {1469-7793}, support = {//Lilly Research Scholarship/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis ; Motor Neurons/physiology ; Action Potentials/physiology ; }, } @article {pmid37983951, year = {2024}, author = {Turhan, SA and Karlsson, P and Ozun, Y and Gunes, H and Surucu, S and Toker, E and Isak, B}, title = {Identification of corneal and intra-epidermal axonal swellings in amyotrophic lateral sclerosis.}, journal = {Muscle & nerve}, volume = {69}, number = {1}, pages = {78-86}, doi = {10.1002/mus.27995}, pmid = {37983951}, issn = {1097-4598}, support = {//Novo Nordisk/ ; NNF18OC0052301//PK (Pall Karlsson) is funded by a grant from the Novo Nordisk Foundation/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/pathology ; Axons/pathology ; Cornea/innervation ; Skin/pathology ; Nerve Fibers, Unmyelinated/pathology ; Microscopy, Confocal ; }, abstract = {INTRODUCTION/AIMS: In patients with amyotrophic lateral sclerosis (ALS), axonal spheroids in motor axons have been identified in post-mortem studies. In this study, axonal spheroids and swellings on C-fibers of ALS patients were investigated using corneal confocal microscopy (CCM) and skin biopsy, respectively.

METHODS: Thirty-one ALS patients and 20 healthy subjects were evaluated with CCM to assess corneal nerve-fiber length (CNFL), -fiber density (CNFD), -branch density (CNBD), dendritic cell (DC) density, and axonal spheroids originating from C-fibers (>100 μm[2]). In addition, intraepidermal nerve fiber density (IENFD) and axonal swellings (>1.5 μm) were assessed in skin biopsies obtained from the arms and legs of 22 patients and 17 controls.

RESULTS: In ALS patients, IENFD, CNFD, CNFL, and CNBD were not different from controls. The density of DCs and the number of patients with increased DC density were higher in ALS patients than controls (p = .0005 and p = .008). The number of patients with axonal spheroids was higher than controls (p = .03).

DISCUSSION: Evaluation of DCs and axonal bulbs in C-fibers of ALS patients could provide insights into pathophysiology or potentially serve as biomarkers in ALS.}, } @article {pmid37983563, year = {2024}, author = {Wen, D and Ji, Y and Li, Y and Duan, W and Wang, Y and Li, Z and Tao, M and Liu, Y}, title = {OPTN gene therapy increases autophagy and protects mitochondria in SOD1-G93A-expressing transgenic mice and cells.}, journal = {The FEBS journal}, volume = {291}, number = {4}, pages = {795-813}, doi = {10.1111/febs.17009}, pmid = {37983563}, issn = {1742-4658}, support = {H2021206048//Hebei Natural Science Foundation/ ; }, mesh = {Mice ; Animals ; *Amyotrophic Lateral Sclerosis/genetics/therapy/metabolism ; Mice, Transgenic ; Superoxide Dismutase-1/genetics/metabolism/pharmacology ; Superoxide Dismutase/genetics/metabolism ; Autophagy/genetics ; Mitochondria/genetics/metabolism ; Disease Models, Animal ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by progressive motor neuron (MN) death. Mutation of the superoxide dismutase 1 (SOD1) gene, which results in abnormal protein aggregation, is one of the causes of familial ALS. Autophagic dysfunction occurs in SOD1-G93A mutant mice as the disease progresses, but the etiology of this disease is still unclear. Optineurin (OPTN) is an adaptor that is involved in autophagy and participates in aggrephagy and mitophagy. Previous studies have established that OPTN mutations contribute to diseases such as glaucoma and ALS. However, the function of OPTN in autophagy and mitophagy has not been intensively investigated in models of ALS. In this study, we assessed the beneficial effect of OPTN on autophagy and mitochondrial function by intrathecally injecting adeno-associated virus 9 (AAV9)-OPTN into SOD1-G93A transgenic mice and by administering lentivirus (LV)-OPTN to cells expressing the SOD1-G93A mutant protein. The expression of voltage-dependent anion channel 1 (VDAC1) was increased and autophagy was elevated after OPTN gene therapy, as shown by a lower level of p62 and a higher level of microtubule-associated protein 1A/1B-light chain 3 (LC3)-II. Moreover, using electron microscopy, we observed a hyperpolarized mitochondrial transmembrane potential and reversal of mitochondrial morphological abnormalities. Furthermore, the protein level of TANK-binding kinase 1 (TBK1) was increased, suggesting that mitophagy was increased. Our findings from both animal and cell line studies strongly suggest that OPTN gene therapy is a powerful strategy to increase autophagy and protect mitochondria to prevent the progression of ALS and could be effective in the treatment of ALS.}, } @article {pmid37982993, year = {2023}, author = {Tsui, A and Kouznetsova, VL and Kesari, S and Fiala, M and Tsigelny, IF}, title = {Role of Senataxin in Amyotrophic Lateral Sclerosis.}, journal = {Journal of molecular neuroscience : MN}, volume = {73}, number = {11-12}, pages = {996-1009}, pmid = {37982993}, issn = {1559-1166}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism ; Motor Neurons/metabolism ; Gene Expression Regulation ; Mutation ; DNA Helicases/genetics ; RNA Helicases/genetics/metabolism ; Multifunctional Enzymes/genetics/metabolism ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive, uncurable neurodegenerative disorder characterized by the degradation of motor neurons leading to muscle impairment, failure, and death. Senataxin, encoded by the SETX gene, is a human helicase protein whose mutations have been linked with ALS onset, particularly in its juvenile ALS4 form. Using senataxin's yeast homolog Sen1 as a model for study, it is suggested that senataxin's N-terminus interacts with RNA polymerase II, whilst its C-terminus engages in helicase activity. Senataxin is heavily involved in transcription regulation, termination, and R-loop resolution, enabled by recruitment and interactions with enzymes such as ubiquitin protein ligase SAN1 and ribonuclease H (RNase H). Senataxin also engages in DNA damage response (DDR), primarily interacting with the exosome subunit Rrp45. The Sen1 mutation E1597K, alongside the L389S and R2136H gain-of-function mutations to senataxin, is shown to cause negative structural and thus functional effects to the protein, thus contributing to a disruption in WT functions, motor neuron (MN) degeneration, and the manifestation of ALS clinical symptoms. This review corroborates and summarizes published papers concerning the structure and function of senataxin as well as the effects of their mutations in ALS pathology in order to compile current knowledge and provide a reference for future research. The findings compiled in this review are indicative of the experimental and therapeutic potential of senataxin and its mutations as a target in future ALS treatment/cure discovery, with some potential therapeutic routes also being discussed in the review.}, } @article {pmid37982655, year = {2024}, author = {Mossa, A and Mayahara, M and Emezue, C and Paun, O}, title = {The Impact of Rapidly Progressing Neurodegenerative Disorders on Caregivers: An Integrative Literature Review.}, journal = {Journal of hospice and palliative nursing : JHPN : the official journal of the Hospice and Palliative Nurses Association}, volume = {26}, number = {2}, pages = {E62-E73}, pmid = {37982655}, issn = {1539-0705}, mesh = {Humans ; *Quality of Life ; Caregivers ; *Amyotrophic Lateral Sclerosis ; Disease Progression ; Death ; }, abstract = {Neurodegenerative disorders affect over 6 million people in the United States. A subset of these patients experiences symptoms that progress rapidly, along with a 5- to 10-year life expectancy (amyotrophic lateral sclerosis). This subgroup often becomes dependent on family caregivers. Managing care demands at the end of life that are brought on by rapid disease progression has a negative impact on caregiver quality of life. The purpose of this integrative review is to highlight the gaps in the existing body of research on the effect of neuropalliative care on quality of life of this caregiver population. A total of 13 articles met inclusion criteria and were selected for review. The most frequently occurring themes and findings in the literature shed light on neuropalliative care and provided some insight into both caregivers and patients' perspective at the end of life. What sets this population apart from caregivers and patients of other terminal diseases is the nature of disease progression and the rapid life adjustments that come along with it. Integration of neuropalliative has shown to provide additional support for caregivers and patients; however, it remains underused. To promote equitable access to these services, it is necessary to address several structural barriers.}, } @article {pmid37981575, year = {2024}, author = {Shojaie, A and Al Khleifat, A and Sarraf, P and Al-Chalabi, A}, title = {Analysis of non-motor symptoms in amyotrophic lateral sclerosis.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {25}, number = {3-4}, pages = {237-241}, pmid = {37981575}, issn = {2167-9223}, support = {/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/complications/diagnosis/epidemiology ; Surveys and Questionnaires ; Pain/epidemiology/etiology ; }, abstract = {OBJECTIVE: We investigated non-motor symptoms in ALS using sequential questionnaires; here we report the findings of the second questionnaire.

METHODS: A social media platform (Twitter, now known as X) was used to publicize the questionnaires. Data were downloaded from SurveyMonkey and analyzed by descriptive statistics, comparison of means, and regression models.

RESULTS: There were 182 people with ALS and 57 controls. The most important non-motor symptoms were cold limbs (60.4% cases, 14% controls, p = 9.67 x 10[-10]) and appetite loss (29.7% cases, 5.3% controls, p = 1.6 x 10[-4]). The weaker limb was most likely to feel cold (p = 9.67 x 10[-10]), and symptoms were more apparent in the evening and night. Appetite loss was reported as due to feeling full and the time taken to eat. People with ALS experienced medium-intensity pain, more usually shock-like pain than burning or cold-like pain, although the most prevalent type of pain was non-differentiated.

CONCLUSIONS: Non-motor symptoms are an important feature of ALS. Further investigation is needed to understand their physiological basis and whether they represent phenotypic differences useful for subtyping ALS.}, } @article {pmid37981468, year = {2024}, author = {Sutter, PA and Lavoie, ER and Lombardo, ET and Pinter, MK and Crocker, SJ}, title = {Emerging Role of Astrocyte-Derived Extracellular Vesicles as Active Participants in CNS Neuroimmune Responses.}, journal = {Immunological investigations}, volume = {53}, number = {1}, pages = {26-39}, pmid = {37981468}, issn = {1532-4311}, support = {F30 NS129238/NS/NINDS NIH HHS/United States ; R01 NS131327/NS/NINDS NIH HHS/United States ; R21 NS125332/NS/NINDS NIH HHS/United States ; R56 NS099359/NS/NINDS NIH HHS/United States ; }, mesh = {Humans ; *Astrocytes ; *Extracellular Vesicles ; Cell Communication ; Biomarkers ; }, abstract = {Astrocyte-derived extracellular vesicles (ADEVs) have garnered attention as a fundamental mechanism of intercellular communication in health and disease. In the context of neurological diseases, for which prodromal diagnosis would be advantageous, ADEVs are also being explored for their potential utility as biomarkers. In this review, we provide the current state of data supporting our understanding on the manifold roles of ADEVs in several common neurological disorders. We also discuss these findings from a unique emerging perspective that ADEVs represent a means by which the central nervous system may broadcast influence over other systems in the body to affect neuroinflammatory processes, with both dual potential to either propagate illness or restore health and homeostasis.}, } @article {pmid37981210, year = {2024}, author = {Kim, Y and Lee, Y and Choo, M and Yun, N and Cho, JW and Oh, YJ}, title = {A surge of cytosolic calcium dysregulates lysosomal function and impairs autophagy flux during cupric chloride-induced neuronal death.}, journal = {The Journal of biological chemistry}, volume = {300}, number = {1}, pages = {105479}, pmid = {37981210}, issn = {1083-351X}, mesh = {*Autophagy/drug effects/genetics ; *Calcium/metabolism ; *Copper/pharmacology ; *Dopaminergic Neurons/cytology/drug effects/metabolism/ultrastructure ; *Lysosomes/metabolism ; Animals ; Mice ; Cell Line ; Cell Survival/drug effects ; Cytosol/metabolism ; }, abstract = {Autophagy is a degradative pathway that plays an important role in maintaining cellular homeostasis. Dysfunction of autophagy is associated with the progression of neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. Although one of the typical features of brain aging is an accumulation of redox-active metals that eventually lead to neurodegeneration, a plausible link between trace metal-induced neurodegeneration and dysregulated autophagy has not been clearly determined. Here, we used a cupric chloride-induced neurodegeneration model in MN9D dopaminergic neuronal cells along with ultrastructural and biochemical analyses to demonstrate impaired autophagic flux with accompanying lysosomal dysfunction. We found that a surge of cytosolic calcium was involved in cupric chloride-induced dysregulated autophagy. Consequently, buffering of cytosolic calcium by calbindin-D28K overexpression or co-treatment with the calcium chelator BAPTA attenuated the cupric chloride-induced impairment in autophagic flux by ameliorating dysregulation of lysosomal function. Thus, these events allowed the rescue of cells from cupric chloride-induced neuronal death. These phenomena were largely confirmed in cupric chloride-treated primary cultures of cortical neurons. Taken together, these results suggest that abnormal accumulation of trace metal elements and a resultant surge of cytosolic calcium leads to neuronal death by impairing autophagic flux at the lysosomal level.}, } @article {pmid37981175, year = {2023}, author = {Wang, C and Cui, Y and Xu, T and Zhou, Y and Yang, R and Wang, T}, title = {New insights into glycogen synthase kinase-3: A common target for neurodegenerative diseases.}, journal = {Biochemical pharmacology}, volume = {218}, number = {}, pages = {115923}, doi = {10.1016/j.bcp.2023.115923}, pmid = {37981175}, issn = {1873-2968}, mesh = {Humans ; *Neurodegenerative Diseases/drug therapy/metabolism ; Glycogen Synthase Kinase 3 ; *Parkinson Disease ; *Alzheimer Disease ; *Diabetes Mellitus/drug therapy ; Glycogen Synthase Kinase 3 beta ; }, abstract = {Glycogen synthase kinase 3 (GSK-3) is a highly conserved protein serine/threonine kinase that plays a central role in a wide variety of cellular processes to coordinate catabolic and anabolic pathways and regulate cell growth and fate. There is increasing evidence showing that abnormal glycogen synthase kinase 3 (GSK-3) is associated with the pathogenesis and progression of many disorders, such as cancer, diabetes, psychiatric diseases, and neurodegenerative diseases. In this review, we summarize recent findings about the regulatory role of GSK-3 in the occurrence and development of multiple neurodegenerative diseases, mainly focusing on Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. The aim of this study is to provide new insight into the shared working mechanism of GSK-3 as a therapeutic target of multiple neurodegenerative diseases.}, } @article {pmid37980296, year = {2024}, author = {He, D and Liu, Y and Dong, S and Shen, D and Yang, X and Hao, M and Yin, X and He, X and Li, Y and Wang, Y and Liu, M and Wang, J and Chen, X and Cui, L}, title = {The prognostic value of systematic genetic screening in amyotrophic lateral sclerosis patients.}, journal = {Journal of neurology}, volume = {271}, number = {3}, pages = {1385-1396}, pmid = {37980296}, issn = {1432-1459}, support = {XDB39040000//Strategic Priority Research Program (Pilot study) "Biological basis of aging and therapeutic strategies" of the Chinese Academy of Sciences/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/genetics ; Prognosis ; *Neurodegenerative Diseases/genetics ; Genetic Association Studies ; Genetic Testing ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with complex genetic architecture. Emerging evidence has indicated comorbidity between ALS and autoimmune conditions, suggesting a potential shared genetic basis. The objective of this study is to assess the prognostic value of systematic screening for rare deleterious mutations in genes associated with ALS and aberrant inflammatory responses.

METHODS: A discovery cohort of 494 patients and a validation cohort of 69 patients were analyzed in this study, with population-matched healthy subjects (n = 4961) served as controls. Whole exome sequencing (WES) was performed to identify rare deleterious variants in 50 ALS genes and 1177 genes associated with abnormal inflammatory responses. Genotype-phenotype correlation was assessed, and an integrative prognostic model incorporating genetic and clinical factors was constructed.

RESULTS: In the discovery cohort, 8.1% of patients carried confirmed ALS variants, and an additional 15.2% of patients carried novel ALS variants. Gene burden analysis revealed 303 immune-implicated genes with enriched rare variants, and 13.4% of patients harbored rare deleterious variants in these genes. Patients with ALS variants exhibited a more rapid disease progression (HR 2.87 [95% CI 2.03-4.07], p < 0.0001), while no significant effect was observed for immune-implicated variants. The nomogram model incorporating genetic and clinical information demonstrated improved accuracy in predicting disease outcomes (C-index, 0.749).

CONCLUSION: Our findings enhance the comprehension of the genetic basis of ALS within the Chinese population. It also appears that rare deleterious mutations occurring in immune-implicated genes exert minimal influence on the clinical trajectories of ALS patients.}, } @article {pmid37979250, year = {2024}, author = {Chen, K and Gao, T and Liu, Y and Zhu, K and Wang, T and Zeng, P}, title = {Identifying risk loci for FTD and shared genetic component with ALS: A large-scale multitrait association analysis.}, journal = {Neurobiology of aging}, volume = {134}, number = {}, pages = {28-39}, doi = {10.1016/j.neurobiolaging.2023.09.017}, pmid = {37979250}, issn = {1558-1497}, mesh = {Humans ; *Frontotemporal Dementia/genetics ; *Amyotrophic Lateral Sclerosis/genetics ; Genome-Wide Association Study ; Mutation ; *Pick Disease of the Brain ; Proteins/genetics ; Nuclear Proteins/genetics ; }, abstract = {Current genome-wide association studies of frontotemporal dementia (FTD) are underpowered due to limited samples. Further, common genetic etiologies between FTD and amyotrophic lateral sclerosis (ALS) remain unknown. Using the largest summary statistics of FTD (3526 cases and 9402 controls) and ALS (27,205 cases and 110,881 controls), we found a significant genetic correlation between them (rˆg = 0.637, P = 0.032) and identified 190 FTD-related variants within 5 loci (3p22.1, 5q35.1, 9p21.2, 19p13.11, and 20q13.13). Among these, ALS and FTD had causal variants in 9p21.2 and 19p13.11. Moreover, MOBP (3p22.1), C9orf72 (9p21.2), MOB3B (9p21.2), UNC13A (19p13.11), SLC9A8 (20q13.13), SNAI1 (20q13.13), and SPATA2 (20q13.13) were discovered by both SNP- and gene-level analyses, which together discovered 15 FTD-associated genes, with 10 not detected before (IFNK, RNF114, SLC9A8, SPATA2, SNAI1, SCFD1, POLDIP2, TMEM97, G2E3, and PIGW). Functional analyses showed these genes were enriched in heart left ventricle, kidney cortex, and some brain regions. Overall, this study provides insights into genetic determinants of FTD and shared genetic etiology underlying FTD and ALS.}, } @article {pmid37977335, year = {2023}, author = {Benussi, A and Cantoni, V and Grassi, M and Libri, I and Cotelli, MS and Tarantino, B and Datta, A and Thomas, C and Huber, N and Kärkkäinen, S and Herukka, SK and Haapasalo, A and Filosto, M and Padovani, A and Borroni, B}, title = {Cortico-spinal tDCS in amyotrophic lateral sclerosis: A randomized, double-blind, sham-controlled trial followed by an open-label phase.}, journal = {Brain stimulation}, volume = {16}, number = {6}, pages = {1666-1676}, doi = {10.1016/j.brs.2023.11.008}, pmid = {37977335}, issn = {1876-4754}, mesh = {Humans ; *Transcranial Direct Current Stimulation ; *Amyotrophic Lateral Sclerosis/therapy ; Quality of Life ; Transcranial Magnetic Stimulation ; Double-Blind Method ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive disease for which no curative treatment is currently available.

OBJECTIVE: This study aimed to investigate whether cortico-spinal transcranial direct current stimulation (tDCS) could mitigate symptoms in ALS patients via a randomized, double-blind, sham-controlled trial, followed by an open-label phase.

METHODS: Thirty-one participants were randomized into two groups for the initial controlled phase. At baseline (T0), Group 1 received placebo stimulation (sham tDCS), while Group 2 received cortico-spinal stimulation (real tDCS) for five days/week for two weeks (T1), with an 8-week (T2) follow-up (randomized, double-blind, sham-controlled phase). At the 24-week follow-up (T3), all participants (Groups 1 and 2) received a second treatment of anodal bilateral motor cortex and cathodal spinal stimulation (real tDCS) for five days/week for two weeks (T4). Follow-up evaluations were performed at 32-weeks (T5) and 48-weeks (T6) (open-label phase). At each time point, clinical assessment, blood sampling, and intracortical connectivity measures using transcranial magnetic stimulation (TMS) were evaluated. Additionally, we evaluated survival rates.

RESULTS: Compared to sham stimulation, cortico-spinal tDCS significantly improved global strength, caregiver burden, and quality of life scores, which correlated with the restoration of intracortical connectivity measures. Serum neurofilament light levels decreased among patients who underwent real tDCS but not in those receiving sham tDCS. The number of completed 2-week tDCS treatments significantly influenced patient survival.

CONCLUSIONS: Cortico-spinal tDCS may represent a promising therapeutic and rehabilitative approach for patients with ALS. Further larger-scale studies are necessary to evaluate whether tDCS could potentially impact patient survival.

CLINICAL TRIAL REGISTRATION: NCT04293484.}, } @article {pmid37976792, year = {2023}, author = {Larsson, BJ and Nordin, K and Nygren, I}, title = {Symptoms of anxiety and depression in patients with amyotrophic lateral sclerosis and their relatives during the disease trajectory.}, journal = {Journal of the neurological sciences}, volume = {455}, number = {}, pages = {122780}, doi = {10.1016/j.jns.2023.122780}, pmid = {37976792}, issn = {1878-5883}, mesh = {Humans ; *Depression/epidemiology/diagnosis ; *Amyotrophic Lateral Sclerosis/complications/diagnosis/epidemiology ; Longitudinal Studies ; Prospective Studies ; Anxiety/epidemiology ; }, abstract = {OBJECTS: The aim of this study was to describe the presence of anxiety and depression among patients with Amyotrophic Lateral Sclerosis (ALS) and their relatives from diagnosis and during the disease progression. An additional aim was to explore if the patient's physical function correlated with the patients' or relatives' anxiety and depression.

METHODS: A prospective and longitudinal study, including 33 patients with ALS and their relatives who filled out the Hospital Anxiety and Depression Scale (HADS) at the time of diagnosis and over a period of two years. The patient's physical function was measured with the revised Amyotrophic Lateral Sclerosis Functional and Rating Scale (ALS FRS-R).

RESULTS: The results showed that many patients (45%) and relatives (58%) had symptoms of anxiety and that 13% of the patients and 29% of the relatives had symptoms of depression soon after the patient had been diagnosed with ALS. The prevalence of anxiety decreased over time in the group of patients but remained stable in the group of relatives. Relatives had more symptoms of anxiety compared to patients. There was a correlation between the patient's physical function and HADS in the group of relatives; however, no correlation was found in the group of patients.

CONCLUSION: The results showed that many patients and relatives suffered from symptoms of anxiety quite soon after their diagnosis, and that many relatives had symptoms of anxiety during the disease trajectory. This highlights the need to continuously measure patients' anxiety/depression level but also to pay attention to symptoms among relatives.}, } @article {pmid37975798, year = {2024}, author = {Saini, A and Chawla, PA}, title = {Breaking barriers with tofersen: Enhancing therapeutic opportunities in amyotrophic lateral sclerosis.}, journal = {European journal of neurology}, volume = {31}, number = {2}, pages = {e16140}, pmid = {37975798}, issn = {1468-1331}, mesh = {Adult ; Humans ; *Amyotrophic Lateral Sclerosis/drug therapy/genetics ; Superoxide Dismutase-1/genetics ; *Neurodegenerative Diseases ; Oligonucleotides/therapeutic use ; }, abstract = {BACKGROUND AND PURPOSE: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that primarily affects adults, characterized by muscle weakness resulting from the specific death of motor neurons in the spinal cord and brain. The pathogenesis of ALS is associated with the accumulation of mutant superoxide dismutase 1 (SOD1) proteins and neurofilaments in motor neurons, highlighting the critical need for disease-modifying treatments. Current therapies, such as riluzole and edaravone, provide only symptomatic relief. Recently, tofersen gained approval from the US FDA under the brand name Qalsody as the first and only gene therapy for ALS, addressing a significant pathological aspect of the disease.

METHODS: We carried out a literature survey using PubMed, Scopus, National Institutes of Health, and Biogen for articles published in the English language concerned with "amyotrophic lateral sclerosis", pathophysiology, current treatment, treatment under clinical trial, and the newly approved drug "tofersen" and its detailed summary.

RESULTS: A comprehensive review of the literature on the pathophysiology, available treatment, and newly approved drug for this condition revealed convincing evidence that we are now able to better monitor and treat ALS.

CONCLUSIONS: Although treatment of ALS is difficult, the newly approved drug tofersen has emerged as a potential therapy to slow down the progression of ALS by targeting SOD1 mRNA, representing a significant advancement in the treatment of ALS.}, } @article {pmid37975796, year = {2024}, author = {Witzel, S and Statland, JM and Steinacker, P and Otto, M and Dorst, J and Schuster, J and Barohn, RJ and Ludolph, AC}, title = {Longitudinal course of neurofilament light chain levels in amyotrophic lateral sclerosis-insights from a completed randomized controlled trial with rasagiline.}, journal = {European journal of neurology}, volume = {31}, number = {3}, pages = {e16154}, pmid = {37975796}, issn = {1468-1331}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy ; Intermediate Filaments ; Biomarkers ; Neurofilament Proteins ; Disease Progression ; *Indans ; }, abstract = {BACKGROUND AND PURPOSE: Rasagiline might be disease modifying in patients with amyotrophic lateral sclerosis (ALS). The aim was to evaluate the effect of rasagiline 2 mg/day on neurofilament light chain (NfL), a prognostic biomarker in ALS.

METHODS: In 65 patients with ALS randomized in a 3:1 ratio to rasagiline 2 mg/day (n = 48) or placebo (n = 17) in a completed randomized controlled multicentre trial, NfL levels in plasma were measured at baseline, month 6 and month 12. Longitudinal changes in NfL levels were evaluated regarding treatment and clinical parameters.

RESULTS: Baseline NfL levels did not differ between the study arms and correlated with disease progression rates both pre-baseline (r = 0.64, p < 0.001) and during the study (r = 0.61, p < 0.001). NfL measured at months 6 and 12 did not change significantly from baseline in both arms, with a median individual NfL change of +1.4 pg/mL (interquartile range [IQR] -5.6, 14.2) across all follow-up time points. However, a significant difference in NfL change at month 12 was observed between patients with high and low NfL baseline levels treated with rasagiline (high [n = 13], -6.9 pg/mL, IQR -20.4, 6.0; low [n = 18], +5.9 pg/mL, IQR -1.4, 19.7; p = 0.025). Additionally, generally higher longitudinal NfL variability was observed in patients with high baseline levels, whereas disease progression rates and disease duration at baseline had no impact on the longitudinal NfL course.

CONCLUSION: Post hoc NfL measurements in completed clinical trials are helpful in interpreting NfL data from ongoing and future interventional trials and could provide hypothesis-generating complementary insights. Further studies are warranted to ultimately differentiate NfL response to treatment from other factors.}, } @article {pmid37975632, year = {2024}, author = {Fornage, LB and O'Neil, C and Dowker, SR and Wanta, ER and Lewis, RS and Brown, LH}, title = {Prehospital Intervention Improves Outcomes for Patients Presenting in Atrial Fibrillation with Rapid Ventricular Response.}, journal = {Prehospital emergency care}, volume = {28}, number = {7}, pages = {910-919}, doi = {10.1080/10903127.2023.2283885}, pmid = {37975632}, issn = {1545-0066}, mesh = {Humans ; Retrospective Studies ; Male ; Female ; *Atrial Fibrillation/therapy/drug therapy ; Aged ; *Emergency Medical Services/methods ; Middle Aged ; Adult ; Aged, 80 and over ; Adolescent ; Cohort Studies ; Advanced Cardiac Life Support/methods ; Propensity Score ; Out-of-Hospital Cardiac Arrest/therapy/mortality ; Young Adult ; }, abstract = {OBJECTIVE: To compare outcomes of patients presenting to emergency medical services (EMS) with atrial fibrillation with rapid ventricular response (AF-RVR) who did and did not receive prehospital advanced life support (ALS) rate or rhythm control intervention(s).

METHODS: This retrospective cohort study used the 2021 ESO Data Collaborative (Austin, TX) dataset. We identified 9-1-1 scene responses for patients aged 16 to 100 years old presenting with AF and an initial heart rate ≥ 110 beats per minute (bpm). Prehospital ALS interventions for AF-RVR included medications (e.g., calcium channel blockers, beta blockers, etc.) or electrical cardioversion. Outcome measures included prehospital rate control (i.e., final prehospital heart rate < 110 bpm), emergency department (ED) discharge to home, ED and hospital length of stay, and mortality. We also evaluated prehospital adverse events-specifically bradycardia, hypotension, and cardiac arrest. We used propensity score matching to compare outcomes among treated and untreated patients with similar demographic and clinical characteristics. We determined the average treatment effect on the treated (ATET) with 95% confidence intervals (CI) and the number needed to treat (NNT).

RESULTS: After propensity score matching, prehospital outcomes were available for 4,859 treated patients matched with 4,859 similar untreated patients. Prehospital rate control was more frequent for treated than for untreated patients (41.0% vs. 18.2%, ATET +22.8%, CI: +21.1%; +24.6%, NNT = 5). Hospital outcomes were available for 1,347 treated patients matched with 1,347 similar untreated patients. Treated patients were more likely to be discharged from the ED (37.9% vs. 34.0%, ATET +3.9%, CI: +0.2%; +7.5%, NNT = 26) and less likely to die (4.3% vs. 6.7%, ATET -2.5%, CI: -4.2%; -0.8%, NNT = 40) compared to untreated patients. Hypotension occurred more often in treated patients (ATET +2.6%, CI: +1.5%; +3.7%), but resolved before ED arrival in 73% of affected patients. Otherwise, adverse event rates did not significantly differ for the two groups.

CONCLUSIONS: In this propensity score matched study of patients presenting to EMS with AF-RVR, prehospital ALS interventions were associated with more frequent prehospital rate control, more frequent discharge to home from the ED, and lower mortality.}, } @article {pmid37975411, year = {2025}, author = {Noorbakhsh Varnosfaderani, SM and Sadat Haeri, M and Arian, AS and Yousefi Rad, A and Yazdanpour, M and Mojahedian, F and Yaghoubzad-Maleki, M and Zalpoor, H and Baziyar, P and Nabi-Afjadi, M}, title = {Fighting against amyotrophic lateral sclerosis (ALS) with flavonoids: a computational approach to inhibit superoxide dismutase (SOD1) mutant aggregation.}, journal = {Journal of biomolecular structure & dynamics}, volume = {43}, number = {1}, pages = {419-436}, doi = {10.1080/07391102.2023.2281641}, pmid = {37975411}, issn = {1538-0254}, mesh = {*Amyotrophic Lateral Sclerosis/drug therapy/genetics ; *Flavonoids/pharmacology/chemistry ; Humans ; *Superoxide Dismutase-1/genetics/chemistry/metabolism ; *Molecular Dynamics Simulation ; *Mutation ; Protein Aggregates/drug effects ; Molecular Docking Simulation ; Protein Binding ; Hydrogen Bonding ; Protein Aggregation, Pathological/drug therapy/genetics ; Hydrophobic and Hydrophilic Interactions ; Thermodynamics ; }, abstract = {Protein aggregation is a biological process that occurs when proteins misfold. Misfolding and aggregation of human superoxide dismutase (hSOD1) cause a neurodegenerative disease called amyotrophic lateral sclerosis (ALS). Among the mutations occurring, targeting the E21K mutation could be a good choice to understand the pathological mechanism of SOD1 in ALS, whereof it significantly reduces life hopefulness in patients. Naturally occurring polyphenolic flavonoids have been suggested as a way to alleviate the amyloidogenic behavior of proteins. In this study, computational tools were used to identify promising flavonoid compounds that effectively inhibit the pathogenic behavior of the E21K mutant. Initial screening identified Pelargonidin, Curcumin, and Silybin as promising leads. Molecular dynamics (MD) simulations showed that the binding of flavonoids to the mutated SOD1 caused changes in the protein stability, hydrophobicity, flexibility, and restoration of lost hydrogen bonds. Secondary structure analysis indicated that the protein destabilization and the increased propensity of β-sheet caused by the mutation were restored to the wild-type state upon binding of flavonoids. Free energy landscape (FEL) analysis was also used to differentiate aggregation, and results showed that Silybin followed by Pelargonidin had the most therapeutic efficacy against the E21K mutant SOD1. Therefore, these flavonoids hold great potential as highly effective inhibitors in mitigating ALS's fatal and insuperable effects.Communicated by Ramaswamy H. Sarma.}, } @article {pmid37975189, year = {2024}, author = {Lee, I and Mitsumoto, H and Lee, S and Kasarskis, E and Rosenbaum, M and Factor-Litvak, P and Nieves, JW}, title = {Higher Glycemic Index and Glycemic Load Diet Is Associated with Slower Disease Progression in Amyotrophic Lateral Sclerosis.}, journal = {Annals of neurology}, volume = {95}, number = {2}, pages = {217-229}, pmid = {37975189}, issn = {1531-8249}, support = {K23 NS131586/NS/NINDS NIH HHS/United States ; K23NS131586/NS/NINDS NIH HHS/United States ; R01ES016348/ES/NIEHS NIH HHS/United States ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis ; Cohort Studies ; Glycemic Index ; Prospective Studies ; *Glycemic Load ; Diet ; Disease Progression ; }, abstract = {OBJECTIVE: High-caloric diets may slow the progression of amyotrophic lateral sclerosis; however, key macronutrients have not been identified. We examined whether dietary macronutrients are associated with the rate of progression and length of survival among the prospective cohort study participants.

METHODS: Participants with a confirmed diagnosis of sporadic amyotrophic lateral sclerosis enrolled in the Multicenter Cohort Study of Oxidative Stress were included (n = 304). We evaluated baseline macronutrient intake assessed by food frequency questionnaire in relation to change in revised amyotrophic lateral sclerosis functional rating scale total-score, and tracheostomy-free survival using linear regression and Cox proportional hazard models. Baseline age, sex, disease duration, diagnostic certainty, body mass index, bulbar onset, revised amyotrophic lateral sclerosis functional rating scale total-score, and forced vital capacity were included as covariates.

RESULTS: Baseline higher glycemic index and load were associated with less decline of revised amyotrophic lateral sclerosis functional rating scale total score at 3-month follow-up (β = -0.13, 95% CI -0.2, -0.01, p = 0.03) and (β = -0.01, 95% CI -0.03, -0.0007, p = 0.04), respectively. Glycemic index second-quartile, third-quartile, and fourth-quartile groups were associated with less decline at 3 months by 1.9 (95% CI -3.3, -0.5, p = 0.008), 2.0 (95% CI -3.3, -0.6, p = 0.006), and 1.6 (95% CI -3.0, -0.2, p = 0.03) points compared with the first-quartile group; the glycemic load fourth-quartile group had 1.4 points less decline compared with the first-quartile group (95% CI -2.8, 0.1, p = 0.07). Higher glycemic index was associated with a trend toward longer tracheostomy-free survival (HR 0.97, 95% CI 0.93, 1.00, p = 0.07).

INTERPRETATION: Higher dietary glycemic index and load are associated with slower disease progression in amyotrophic lateral sclerosis. ANN NEUROL 2024;95:217-229.}, } @article {pmid37974959, year = {2023}, author = {Bhargava, S and Kulkarni, R and Dewangan, B and Kulkarni, N and Jiaswar, C and Kumar, K and Kumar, A and Bodhe, PR and Kumar, H and Sahu, B}, title = {Microtubule stabilising peptides: new paradigm towards management of neuronal disorders.}, journal = {RSC medicinal chemistry}, volume = {14}, number = {11}, pages = {2192-2205}, pmid = {37974959}, issn = {2632-8682}, abstract = {Neuronal cells made of soma, axon, and dendrites are highly compartmentalized and possess a specialized transport system that can convey long-distance electrical signals for the cross-talk. The transport system is made up of microtubule (MT) polymers and MT-binding proteins. MTs play vital and diverse roles in various cellular processes. Therefore, defects and dysregulation of MTs and their binding proteins lead to many neurological disorders as exemplified by Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis, Huntington's disease, and many others. MT-stabilising agents (MSAs) altering the MT-associated protein connections have shown great potential for several neurodegenerative disorders. Peptides are an important class of molecules with high specificity, biocompatibility and are devoid of side effects. In the past, peptides have been explored in various neuronal disorders as therapeutics. Davunetide, a MT-stabilising octapeptide, has entered into phase II clinical trials for schizophrenia. Numerous examples of peptides emerging as MSAs reflect the emergence of a new paradigm for peptides which can be explored further as drug candidates for neuronal disorders. Although small molecule-based MSAs have been reviewed in the past, there is no systematic review in recent years focusing on peptides as MSAs apart from davunetide in 2013. Therefore, a systematic updated review on MT stabilising peptides may shed light on many hidden aspects and enable researchers to develop new therapies for diseases related to the CNS. In this review we have summarised the recent examples of peptides as MSAs.}, } @article {pmid37974279, year = {2023}, author = {Pelaez, MC and Desmeules, A and Gelon, PA and Glasson, B and Marcadet, L and Rodgers, A and Phaneuf, D and Pozzi, S and Dutchak, PA and Julien, JP and Sephton, CF}, title = {Neuronal dysfunction caused by FUSR521G promotes ALS-associated phenotypes that are attenuated by NF-κB inhibition.}, journal = {Acta neuropathologica communications}, volume = {11}, number = {1}, pages = {182}, pmid = {37974279}, issn = {2051-5960}, support = {RGPIN-2020-06376//Natural Sciences and Engineering Research Council of Canada/ ; DGECR-2020-00060//Natural Sciences and Engineering Research Council of Canada/ ; RGPIN-2018-06227//Natural Sciences and Engineering Research Council of Canada/ ; DGECR-2018-00093//Natural Sciences and Engineering Research Council of Canada/ ; Junior 1//Fonds de Recherche du Québec - Santé/ ; }, mesh = {Aged ; Animals ; Humans ; Mice ; *Amyotrophic Lateral Sclerosis/pathology ; Disease Progression ; *Frontotemporal Dementia/pathology ; Mice, Transgenic ; Motor Neurons/metabolism ; Mutation ; NF-kappa B/metabolism ; RNA-Binding Protein FUS/genetics/metabolism ; }, abstract = {Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are related neurodegenerative diseases that belong to a common disease spectrum based on overlapping clinical, pathological and genetic evidence. Early pathological changes to the morphology and synapses of affected neuron populations in ALS/FTD suggest a common underlying mechanism of disease that requires further investigation. Fused in sarcoma (FUS) is a DNA/RNA-binding protein with known genetic and pathological links to ALS/FTD. Expression of ALS-linked FUS mutants in mice causes cognitive and motor defects, which correlate with loss of motor neuron dendritic branching and synapses, in addition to other pathological features of ALS/FTD. The role of ALS-linked FUS mutants in causing ALS/FTD-associated disease phenotypes is well established, but there are significant gaps in our understanding of the cell-autonomous role of FUS in promoting structural changes to motor neurons, and how these changes relate to disease progression. Here we generated a neuron-specific FUS-transgenic mouse model expressing the ALS-linked human FUSR521G variant, hFUS[R521G/Syn1], to investigate the cell-autonomous role of FUSR521G in causing loss of dendritic branching and synapses of motor neurons, and to understand how these changes relate to ALS-associated phenotypes. Longitudinal analysis of mice revealed that cognitive impairments in juvenile hFUS[R521G/Syn1] mice coincide with reduced dendritic branching of cortical motor neurons in the absence of motor impairments or changes in the neuromorphology of spinal motor neurons. Motor impairments and dendritic attrition of spinal motor neurons developed later in aged hFUS[R521G/Syn1] mice, along with FUS cytoplasmic mislocalisation, mitochondrial abnormalities and glial activation. Neuroinflammation promotes neuronal dysfunction and drives disease progression in ALS/FTD. The therapeutic effects of inhibiting the pro-inflammatory nuclear factor kappa B (NF-κB) pathway with an analog of Withaferin A, IMS-088, were assessed in symptomatic hFUS[R521G/Syn1] mice and were found to improve cognitive and motor function, increase dendritic branches and synapses of motor neurons, and attenuate other ALS/FTD-associated pathological features. Treatment of primary cortical neurons expressing FUSR521G with IMS-088 promoted the restoration of dendritic mitochondrial numbers and mitochondrial activity to wild-type levels, suggesting that inhibition of NF-κB permits the restoration of mitochondrial stasis in our models. Collectively, this work demonstrates that FUSR521G has a cell-autonomous role in causing early pathological changes to dendritic and synaptic structures of motor neurons, and that these changes precede motor defects and other well-known pathological features of ALS/FTD. Finally, these findings provide further support that modulation of the NF-κB pathway in ALS/FTD is an important therapeutic approach to attenuate disease.}, } @article {pmid37974227, year = {2023}, author = {Awuah, WA and Ahluwalia, A and Ghosh, S and Roy, S and Tan, JK and Adebusoye, FT and Ferreira, T and Bharadwaj, HR and Shet, V and Kundu, M and Yee, ALW and Abdul-Rahman, T and Atallah, O}, title = {The molecular landscape of neurological disorders: insights from single-cell RNA sequencing in neurology and neurosurgery.}, journal = {European journal of medical research}, volume = {28}, number = {1}, pages = {529}, pmid = {37974227}, issn = {2047-783X}, mesh = {Humans ; *Neurosurgery ; Neurosurgical Procedures ; *Neurology ; *Brain Neoplasms/genetics ; Sequence Analysis, RNA ; Tumor Microenvironment ; }, abstract = {Single-cell ribonucleic acid sequencing (scRNA-seq) has emerged as a transformative technology in neurological and neurosurgical research, revolutionising our comprehension of complex neurological disorders. In brain tumours, scRNA-seq has provided valuable insights into cancer heterogeneity, the tumour microenvironment, treatment resistance, and invasion patterns. It has also elucidated the brain tri-lineage cancer hierarchy and addressed limitations of current models. Neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis have been molecularly subtyped, dysregulated pathways have been identified, and potential therapeutic targets have been revealed using scRNA-seq. In epilepsy, scRNA-seq has explored the cellular and molecular heterogeneity underlying the condition, uncovering unique glial subpopulations and dysregulation of the immune system. ScRNA-seq has characterised distinct cellular constituents and responses to spinal cord injury in spinal cord diseases, as well as provided molecular signatures of various cell types and identified interactions involved in vascular remodelling. Furthermore, scRNA-seq has shed light on the molecular complexities of cerebrovascular diseases, such as stroke, providing insights into specific genes, cell-specific expression patterns, and potential therapeutic interventions. This review highlights the potential of scRNA-seq in guiding precision medicine approaches, identifying clinical biomarkers, and facilitating therapeutic discovery. However, challenges related to data analysis, standardisation, sample acquisition, scalability, and cost-effectiveness need to be addressed. Despite these challenges, scRNA-seq has the potential to transform clinical practice in neurological and neurosurgical research by providing personalised insights and improving patient outcomes.}, } @article {pmid37973672, year = {2023}, author = {Lo Giudice, M and Cocco, A and Reggiardo, G and Lalli, S and Albanese, A}, title = {Tauro-Urso-Deoxycholic Acid Trials in Amyotrophic Lateral Sclerosis: What is Achieved and What to Expect.}, journal = {Clinical drug investigation}, volume = {43}, number = {12}, pages = {893-903}, pmid = {37973672}, issn = {1179-1918}, support = {755094//Horizon 2020 Framework Programme/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy ; Phenylbutyrates ; Taurochenodeoxycholic Acid/adverse effects ; }, abstract = {Phase II studies on tauro-urso-deoxycholic acid (TUDCA) raised the promise of safety and efficacy in patients with amyotrophic lateral sclerosis, a currently incurable and devastating disease. We review the available evidence on the efficacy and safety of TUDCA, administered alone or in combination, by analyzing and comparing published and ongoing studies on amyotrophic lateral sclerosis. Two independent phase II studies (using TUDCA solo or combined with sodium phenylbutyrate) showed similar efficacy in slowing disease progression measured by functional scales. One open-label follow-up TUDCA+sodium phenylbutyrate study suggested a benefit on survival. Two subsequent phase III studies with TUDCA (solo or combined with sodium phenylbutyrate) have been initiated and are currently ongoing. Their completion is expected by the end of 2023 and beginning of 2024. Evidence collected by phase II studies indicates that there are no safety concerns in patients with amyotrophic lateral sclerosis. The efficacy shown in phase II studies was considered sufficient to grant approval in some countries but not in others, owing to discrepant views on the strength of evidence. It will be necessary to wait for the results of ongoing phase III studies to attain a full appreciation of these data.}, } @article {pmid37973064, year = {2024}, author = {Lisi, E and Abellan, JJ}, title = {Statistical analysis of actigraphy data with generalised additive models.}, journal = {Pharmaceutical statistics}, volume = {23}, number = {3}, pages = {308-324}, doi = {10.1002/pst.2350}, pmid = {37973064}, issn = {1539-1612}, support = {//GlaxoSmithKline/ ; }, mesh = {Humans ; *Actigraphy/statistics & numerical data/methods ; *Models, Statistical ; Exercise/physiology ; Data Interpretation, Statistical ; Amyotrophic Lateral Sclerosis/physiopathology/diagnosis ; Pulmonary Disease, Chronic Obstructive/physiopathology/diagnosis ; Time Factors ; }, abstract = {There is a growing interest in the use of physical activity data in clinical studies, particularly in diseases that limit mobility in patients. High-frequency data collected with digital sensors are typically summarised into actigraphy features aggregated at epoch level (e.g., by minute). The statistical analysis of such volume of data is not straightforward. The general trend is to derive metrics, capturing specific aspects of physical activity, that condense (say) a week worth of data into a single numerical value. Here we propose to analyse the entire time-series data using Generalised Additive Models (GAMs). GAMs are semi-parametric models that allow inclusion of both parametric and non-parametric terms in the linear predictor. The latter are smooth terms (e.g., splines) and, in the context of actigraphy minute-by-minute data analysis, they can be used to assess daily patterns of physical activity. This in turn can be used to better understand changes over time in longitudinal studies as well as to compare treatment groups. We illustrate the application of GAMs in two clinical studies where actigraphy data was collected: a non-drug, single-arm study in patients with amyotrophic lateral sclerosis, and a physical-activity sub-study included in a phase 2b clinical trial in patients with chronic obstructive pulmonary disease.}, } @article {pmid37972988, year = {2024}, author = {Ando, T and Riku, Y and Akagi, A and Miyahara, H and Uematsu, T and Aiba, I and Sone, J and Katsuno, M and Yoshida, M and Iwasaki, Y}, title = {Degeneration of olivospinal tract in the upper cervical spinal cord of multiple system atrophy patients: Reappraisal of Helweg's triangular tract.}, journal = {Brain pathology (Zurich, Switzerland)}, volume = {34}, number = {3}, pages = {e13226}, pmid = {37972988}, issn = {1750-3639}, support = {//Health, Labor, and Welfare Sciences Research Grants/ ; 30-8//Intramural Research Grant for Neurological and Psychiatric Disorders from the NCNP/ ; JP22wm0425019//Japan Agency for Medical Research and Development/ ; JP23K06935//JSPS KAKENHI/ ; //The HORI Science and Arts Foundation/ ; NFRCH 23-0002//The Japanese Red Cross Aichi Medical Center Nagoya Daiichi Hospital Research Grant/ ; //The Ministry of Health, Labor, and Welfare, Japan/ ; //The Research Committee of CNS Degenerative Diseases, Research on Policy Planning and Evaluation for Rare and Intractable Diseases/ ; }, mesh = {Adult ; Humans ; *Multiple System Atrophy/metabolism ; alpha-Synuclein/metabolism ; *Cervical Cord/metabolism ; *Olivopontocerebellar Atrophies ; }, abstract = {Multiple system atrophy (MSA) is an adult-onset neurodegenerative disorder that presents with variable combinations of autonomic dysfunction, cerebellar ataxia, parkinsonism, and pyramidal signs. The inferior olivary nucleus is targeted in MSA, with a phenotype of olivopontocerebellar atrophy in particular, and involvement of the olivocerebellar tract is well known. However, degeneration of the olivospinal tract has not been studied in MSA. We examined 97 spinal cords from consecutively autopsied patients with MSA. Myelin staining revealed that 22 cords (22.7%) had small, bilateral, triangular-shaped tract degeneration in the boundary of the anterior and lateral funiculi, which appeared continuously from C1 to C5. The anatomical pathway of the degenerated tract was consistent with the description of the olivospinal tract provided by Helweg in 1888. The MSA patients showing degeneration of this tract were younger at disease onset (average: 56.4 ± 8.7 years, range: 42-74), and had longer disease duration (average: 10.1 ± 4.8 years, range: 2-25) and more severe olivopontocerebellar changes compared to other MSA patients. Quantitative analyses revealed that patients with olivospinal tract degeneration had a lower neuronal density in the inferior olivary nucleus compared to other patients. Microglial density in this tract was negatively correlated with the neuronal density in the inferior olivary nucleus. The densities of glial cytoplasmic inclusions in the inferior olivary nucleus and in the olivospinal tract were strongly correlated with each other. Neurologically healthy controls (n = 22) and disease controls with Lewy body disease (n = 30), amyotrophic lateral sclerosis (n = 30), and progressive supranuclear palsy (n = 30) did not present the olivospinal tract degeneration. Our results indicate an impairment of the neural connection between the inferior olivary nucleus and the spinal cord in MSA patients, which may develop in a descending manner.}, } @article {pmid37972860, year = {2023}, author = {Rizzuti, M and Sali, L and Melzi, V and Scarcella, S and Costamagna, G and Ottoboni, L and Quetti, L and Brambilla, L and Papadimitriou, D and Verde, F and Ratti, A and Ticozzi, N and Comi, GP and Corti, S and Gagliardi, D}, title = {Genomic and transcriptomic advances in amyotrophic lateral sclerosis.}, journal = {Ageing research reviews}, volume = {92}, number = {}, pages = {102126}, doi = {10.1016/j.arr.2023.102126}, pmid = {37972860}, issn = {1872-9649}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/therapy ; Transcriptome/genetics ; Gene Expression Profiling/methods ; *MicroRNAs/genetics/metabolism ; Biomarkers ; Epigenomics ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder and the most common motor neuron disease. ALS shows substantial clinical and molecular heterogeneity. In vitro and in vivo models coupled with multiomic techniques have provided important contributions to unraveling the pathomechanisms underlying ALS. To date, despite promising results and accumulating knowledge, an effective treatment is still lacking. Here, we provide an overview of the literature on the use of genomics, epigenomics, transcriptomics and microRNAs to deeply investigate the molecular mechanisms developing and sustaining ALS. We report the most relevant genes implicated in ALS pathogenesis, discussing the use of different high-throughput sequencing techniques and the role of epigenomic modifications. Furthermore, we present transcriptomic studies discussing the most recent advances, from microarrays to bulk and single-cell RNA sequencing. Finally, we discuss the use of microRNAs as potential biomarkers and promising tools for molecular intervention. The integration of data from multiple omic approaches may provide new insights into pathogenic pathways in ALS by shedding light on diagnostic and prognostic biomarkers, helping to stratify patients into clinically relevant subgroups, revealing novel therapeutic targets and supporting the development of new effective therapies.}, } @article {pmid37971544, year = {2024}, author = {Fergany, A and Zong, C and Ekuban, FA and Wu, B and Ueha, S and Shichino, S and Matsushima, K and Iwakura, Y and Ichihara, S and Ichihara, G}, title = {Transcriptome analysis of the cerebral cortex of acrylamide-exposed wild-type and IL-1β-knockout mice.}, journal = {Archives of toxicology}, volume = {98}, number = {1}, pages = {181-205}, pmid = {37971544}, issn = {1432-0738}, support = {17H06396//Japan Society for the Promotion of Science London/ ; 19H04279//Japan Society for the Promotion of Science London/ ; }, mesh = {Animals ; Mice ; *Acrylamide/toxicity ; Brain ; Cerebral Cortex ; Gene Expression Profiling ; Mice, Inbred C57BL ; *Neurotoxicity Syndromes/genetics ; }, abstract = {Acrylamide is an environmental electrophile that has been produced in large amounts for many years. There is concern about the adverse health effects of acrylamide exposure due to its widespread industrial use and also presence in commonly consumed foods and others. IL-1β is a key cytokine that protects the brain from inflammatory insults, but its role in acrylamide-induced neurotoxicity remains unknown. We reported recently that deletion of IL-1β gene exacerbates ACR-induced neurotoxicity in mice. The aim of this study was to identify genes or signaling pathway(s) involved in enhancement of ACR-induced neurotoxicity by IL-1β gene deletion or ACR-induced neurotoxicity to generate a hypothesis mechanism explaining ACR-induced neurotoxicity. C57BL/6 J wild-type and IL-1β KO mice were exposed to ACR at 0, 12.5, 25 mg/kg by oral gavage for 7 days/week for 4 weeks, followed by extraction of mRNA from mice cerebral cortex for RNA sequence analysis. IL-1β deletion altered the expression of genes involved in extracellular region, including upregulation of PFN1 gene related to amyotrophic lateral sclerosis and increased the expression of the opposite strand of IL-1β. Acrylamide exposure enhanced mitochondria oxidative phosphorylation, synapse and ribosome pathways, and activated various pathways of different neurodegenerative diseases, such as Alzheimer disease, Parkinson disease, Huntington disease, and prion disease. Protein network analysis suggested the involvement of different proteins in related to learning and cognitive function, such as Egr1, Egr2, Fos, Nr4a1, and Btg2. Our results identified possible pathways involved in IL-1β deletion-potentiated and ACR-induced neurotoxicity in mice.}, } @article {pmid37968433, year = {2024}, author = {Quattrocchi, S and Bonan, L and Cirillo, L and Avoni, P and Di Stasi, V and Rizzo, G and Liguori, R and Vacchiano, V}, title = {Bibrachial amyotrophy as a rare manifestation of intraspinal fluid collection: a case report and systematic review.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {45}, number = {5}, pages = {2279-2288}, pmid = {37968433}, issn = {1590-3478}, mesh = {Humans ; Male ; Middle Aged ; *Magnetic Resonance Imaging ; Electromyography ; Motor Neuron Disease/diagnosis/complications ; }, abstract = {INTRODUCTION: Intraspinal cerebrospinal fluid (CSF) collection has been reported as a rare cause of lower motor neuron (LMN) disorder. We report a case of bibrachial diplegia associated with intraspinal CSF collection and perform a systematic literature review.

PATIENT AND METHODS: A 52-year-old man developed a bibrachial amyotrophy over 6 years, confirmed by the presence of cervical subacute neurogenic changes at electromyography (EMG). Brain magnetic resonance imaging (MRI) revealed cerebral siderosis, while spine MRI showed a ventral longitudinal intraspinal fluid collection (VLISFC) from C2 to L2. No CSF leakage was localized at myelography; a conservative treatment was chosen. We searched for all published cases until 30th April 2023 and extrapolated data of 44 patients reported in 27 publications.

RESULTS: We observed a male predominance, a younger disease onset compared to amyotrophic lateral sclerosis, and a quite long disease duration, highlighting a slow disease progression. LMN signs were more frequently bilateral, mostly involving C5-C6 myotomes. Around 61% of patients presented additional symptoms, but only three referred to a history of headache. Accordingly, CSF opening pressure was mostly normal. Spinal MRI revealed the presence of VLISFC and in some cases myelomalacia. EMG patterns displayed both chronic and subacute neurogenic change in the cervical region. The disease course mainly depended on the treatment choice, which was mostly represented by a surgical approach when a specific dural defect was detected by imaging.

CONCLUSION: Bibrachial diplegia due to VLISFC can be a treatable cause of focal amyotrophy and presents some clinical and radiological "red flags" which cannot be missed by a clinical neurologist.}, } @article {pmid37968324, year = {2023}, author = {Beni, T and Borselli, D and Bonechi, L and Lombardi, L and Gonzi, S and Melelli, L and Turchetti, MA and Fanò, L and D'Alessandro, R and Gigli, G and Casagli, N}, title = {Laser scanner and UAV digital photogrammetry as support tools for cosmic-ray muon radiography applications: an archaeological case study from Italy.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {19983}, pmid = {37968324}, issn = {2045-2322}, abstract = {The use of light detection and ranging technologies, i.e. terrestrial laser scanner (TLS), airborne laser scanner (ALS) and mobile laser scanner (MLS), together with the unmanned aerial vehicles digital photogrammetry (UAV-DP) and satellite data are proving to be fundamental tools to carry out reliable muographic measurement campaigns. The main purpose of this paper is to propose a workflow to correctly plan and exploit these types of data for muon radiography aims. To this end, a real case study is presented: searching for hidden tombs in the Etruscan necropolis of Palazzone (Umbria, Italy). A high-resolution digital elevation model (DEM) and three-dimensional models of the ground surface/sub-surface of the study area were created by merging data obtained using different survey methods to achieve the most accurate three-dimensional environment. Indeed, the simulated muon flux transmission used to infer relative transmission values, and the estimated density distribution, depends on the reliability of the three-dimensional reconstructed ground surface model. The aim of this study is to provide knowledge on the use of TLS and UAV-DP data and GPS-acquired points within the transmission-based muography process and how these data could improve or worsen the muon imaging results. Moreover, this study confirmed that muography applications require a multidisciplinary approach.}, } @article {pmid37967540, year = {2023}, author = {Jalal Jumaah, T and Faal Siahkal, S and Behboodi Moghadam, Z and Ebrahimi, E}, title = {The Effect of Yoga on Maternal Anxiety in Women with Excessive Gestational Weight Gain: A Randomized Controlled Trial.}, journal = {Complementary medicine research}, volume = {30}, number = {6}, pages = {517-524}, doi = {10.1159/000534776}, pmid = {37967540}, issn = {2504-2106}, mesh = {Pregnancy ; Infant, Newborn ; Humans ; Female ; *Yoga ; *Gestational Weight Gain ; Anxiety/therapy ; Iran ; }, abstract = {BACKGROUND: Excessive gestational weight gain (EGWG) and anxiety are comorbid conditions that increase the risk of adverse maternal and neonatal outcomes. This study was conducted to investigate the effect of yoga on the anxiety of women with EGWG.

MATERIALS AND METHODS: This randomized controlled trial was performed on EGWG pregnant women referring to comprehensive health centers in Qom city, Iran, between October 2021 and August 2022. Eighty-eight participants were assigned to the intervention (N = 44) and control (N = 44) groups. The experimental group participated in six sessions of 90-min yoga classes, and the control group only received routine care. Two questionnaires including a demographic information questionnaire and the State-Trait Anxiety Inventory (STAI) questionnaire were used for data collection. Data were analyzed using SPSS software version 22.

RESULTS: The results of this study showed a statistically significant difference between the two groups in terms of trait anxiety (25.84 ± 3.45 vs. 57.38 ± 8.07; p < 0.05) and state anxiety (27.93 ± 3.72 vs. 60.13 ± 8.13; p < 0.05) after intervention. On the other hand, the trait and state anxiety rates were stable in the experimental group before and after intervention, while they increased to the severe form of anxiety in the control group (effect size = -21.84 ± 10.66 vs. -19.43 ± 8.44).

CONCLUSION: The result of this study showed that yoga has a positive effect on the anxiety of pregnant women with EGWG and can be used as a preventive or complementary solution to control the anxiety of these mothers.

UNLABELLED: HintergrundExzessive Gewichtszunahme in der Schwangerschaft (EGWG) und Angst sind Komorbiditäten, die das Risiko für einen ungünstigen Verlauf für Mutter und Kind erhöhen. Diese Studie wurde durchgeführt, um die Auswirkung von Yoga auf Angst bei Frauen mit exzessiver Gewichtszunahme in der Schwangerschaft zu untersuchen.Material und MethodenDiese randomisierte, kontrollierte Studie wurde bei Schwangeren mit EGWG durchgeführt, die sich zwischen Oktober 2021 und August 2022 an Zentren für ganzheitliche Gesundheit in der Stadt Ghom im Iran vorstellten. 88 Teilnehmerinnen wurden einer Interventions- (N = 44) und einer Kontrollgruppe (N = 44) zugeteilt. Die experimentelle Gruppe nahm an einem Yogakurs von sechsmal 90 minuten Dauer teil, die Kontrollgruppe erhielt lediglich die Standardversorgung. Die Datenerhebung erfolgte mit zwei Fragebögen: einem Fragebogen zu demografischen Angaben und dem State-Trait-Angstinventar (STAI). Die Auswertung der Daten erfolgte mit SPSS-Software, Version 22.ErgebnisseDie Ergebnisse dieser Studie zeigten einen statistisch signifikanten Unterschied zwischen beiden Gruppen im Hinblick auf Eigenschaftsangst (25.84 ± 3.45 vs. 57.38 ± 8.07; p < 0.05) und Zustandsangst (27.93 ± 3.72 vs. 60.13 ± 8.13; p < 0.05) nach der Intervention. Auf der anderen Seite waren die Raten von Eigenschafts- und Zustandsangst in der experimentellen Gruppe vor und nach der Intervention stabil, während sie in der Kontrollgruppe zur schweren Form von Angst anstiegen (Effektstärke = −21.84 ± 10.66 vs. −19.43 ± 8.44).SchlussfolgerungDie Ergebnisse dieser Studie zeigen, dass Yoga sich bei Schwangeren mit EGWG positive auf Angst auswirkt und als präventive oder komplementäre Lösung zur Beherrschung von Angst bei diesen Müttern eingesetzt werden kann.}, } @article {pmid37967511, year = {2023}, author = {Pavey, N and Hannaford, A and Higashihara, M and van den Bos, M and Kiernan, MC and Menon, P and Vucic, S}, title = {Utility of split hand index with different motor unit number estimation techniques in ALS.}, journal = {Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology}, volume = {156}, number = {}, pages = {175-182}, doi = {10.1016/j.clinph.2023.09.018}, pmid = {37967511}, issn = {1872-8952}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis ; Muscle, Skeletal ; Hand ; Area Under Curve ; Action Potentials/physiology ; Electromyography/methods ; }, abstract = {OBJECTIVE: Utility of the split hand index (SI) in amyotrophic lateral sclerosis (ALS) has been reported when using the compound muscle action potential (CMAP) amplitude method (SICMAP amp). A motor unit number index (MUNIX) based SI method (SIMUNIX) was purported to exhibit higher sensitivity. The present study assessed the clinical utility of SI, derived by CMAP amplitude, MUNIX and MScan-MUNE (SIMScanFit-MUNE) methods, in ALS.

METHODS: Sixty-two consecutive patients with neuromuscular symptoms (36 ALS and 26 ALS-mimics) were prospectively recruited. The SI was derived by dividing the product of the CMAP amplitude, MUNIX and MScan-MUNE values recorded over first dorsal interosseous and abductor pollicis brevis by values recorded over abductor digit minimi.

RESULTS: SICMAP amp, SIMUNIX and SIMScanFit-MUNE were significantly reduced in ALS, with SICMAP amp (area under curve (AUC) = 0.801) and SIMScanFit-MUNE (AUC = 0.805) exhibiting greater diagnostic utility than SIMUNIX (AUC = 0.713). SICMAP amp and SIMScanFit-MUNE exhibited significant correlations with clinical measures of functional disability and weakness of intrinsic hand muscles.

CONCLUSIONS: SI differentiated ALS from mimic disorders, with SICMAP amp and SIMScanFit-MUNE exhibiting greater utility.

SIGNIFICANCE: The split hand index represents could serve as a potential diagnostic biomarker in ALS.}, } @article {pmid37967220, year = {2023}, author = {Watanabe, S and Murata, Y and Oka, Y and Oiwa, K and Horiuchi, M and Iguchi, Y and Komine, O and Sobue, A and Katsuno, M and Ogi, T and Yamanaka, K}, title = {Mitochondria-associated membrane collapse impairs TBK1-mediated proteostatic stress response in ALS.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {120}, number = {47}, pages = {e2315347120}, pmid = {37967220}, issn = {1091-6490}, support = {17H04986 23K06826//Ministry of Education, Culture, Sports, Science and Technology (MEXT)/ ; 18H02740 18H04860 19KK0214 22H00467//Ministry of Education, Culture, Sports, Science and Technology (MEXT)/ ; JP21ek0109426 JP23wm0425014//Japan Agency for Medical Research and Development (AMED)/ ; //Uehara Memorial Foundation (UMF)/ ; //Public Foundation of Chubu Science and Technology Center (CSTC)/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism ; Mitochondria/metabolism ; Mitochondrial Membranes/metabolism ; Endoplasmic Reticulum/metabolism ; Protein Serine-Threonine Kinases/genetics/metabolism ; }, abstract = {The organelle contact site of the endoplasmic reticulum and mitochondria, known as the mitochondria-associated membrane (MAM), is a multifunctional microdomain in cellular homeostasis. We previously reported that MAM disruption is a common pathological feature in amyotrophic lateral sclerosis (ALS); however, the precise role of MAM in ALS was uncovered. Here, we show that the MAM is essential for TANK-binding kinase 1 (TBK1) activation under proteostatic stress conditions. A MAM-specific E3 ubiquitin ligase, autocrine motility factor receptor, ubiquitinated nascent proteins to activate TBK1 at the MAM, which results in ribosomal protein degradation. MAM or TBK1 deficiency under proteostatic stress conditions resulted in increased cellular vulnerability in vitro and motor impairment in vivo. Thus, MAM disruption exacerbates proteostatic stress via TBK1 inactivation in ALS. Our study has revealed a proteostatic mechanism mediated by the MAM-TBK1 axis, highlighting the physiological importance of the organelle contact sites.}, } @article {pmid37966863, year = {2024}, author = {Babcock, CD and Volk, VL and Zeng, W and Hamilton, LD and Shelburne, KB and Fitzpatrick, CK}, title = {Neural-driven activation of 3D muscle within a finite element framework: exploring applications in healthy and neurodegenerative simulations.}, journal = {Computer methods in biomechanics and biomedical engineering}, volume = {27}, number = {16}, pages = {2389-2399}, pmid = {37966863}, issn = {1476-8259}, support = {U01 AR072989/AR/NIAMS NIH HHS/United States ; }, mesh = {Humans ; *Finite Element Analysis ; *Amyotrophic Lateral Sclerosis/physiopathology ; Muscle, Skeletal/physiopathology/physiology ; Computer Simulation ; Models, Biological ; Motor Neurons/physiology ; }, abstract = {This paper presents a novel computational framework for neural-driven finite element muscle models, with an application to amyotrophic lateral sclerosis (ALS). The multiscale neuromusculoskeletal (NMS) model incorporates physiologically accurate motor neurons, 3D muscle geometry, and muscle fiber recruitment. It successfully predicts healthy muscle force and tendon elongation and demonstrates a progressive decline in muscle force due to ALS, dropping from 203 N (healthy) to 155 N (120 days after ALS onset). This approach represents a preliminary step towards developing integrated neural and musculoskeletal simulations to enhance our understanding of neurodegenerative and neurodevelopmental conditions through predictive NMS models.}, } @article {pmid37966813, year = {2024}, author = {Fang, M and Liu, Y and Huang, C and Fan, S}, title = {Targeting stress granules in neurodegenerative diseases: A focus on biological function and dynamics disorders.}, journal = {BioFactors (Oxford, England)}, volume = {50}, number = {3}, pages = {422-438}, doi = {10.1002/biof.2017}, pmid = {37966813}, issn = {1872-8081}, mesh = {Humans ; *Neurodegenerative Diseases/metabolism/pathology ; *Stress Granules/metabolism/genetics ; *Amyotrophic Lateral Sclerosis/metabolism/genetics/pathology ; Alzheimer Disease/metabolism/pathology/genetics ; Huntington Disease/metabolism/genetics/pathology ; Parkinson Disease/metabolism/pathology/genetics ; Animals ; Frontotemporal Dementia/metabolism/pathology/genetics ; Neurons/metabolism/pathology ; }, abstract = {Stress granules (SGs) are membraneless organelles formed by eukaryotic cells in response to stress to promote cell survival through their pleiotropic cytoprotective effects. SGs recruit a variety of components to enhance their physiological function, and play a critical role in the propagation of pathological proteins, a key factor in neurodegeneration. Recent advances indicate that SG dynamic disorders exacerbate neuronal susceptibility to stress in neurodegenerative diseases (NDs) including Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), Huntington's disease (HD) and Parkinson's disease (PD). Here, we outline the biological functions of SGs, highlight SG dynamic disorders in NDs, and emphasize therapeutic approaches for enhancing SG dynamics to provide new insights into ND intervention.}, } @article {pmid37966683, year = {2024}, author = {Ansari, MA and Tripathi, T and Venkidasamy, B and Monziani, A and Rajakumar, G and Alomary, MN and Alyahya, SA and Onimus, O and D'souza, N and Barkat, MA and Al-Suhaimi, EA and Samynathan, R and Thiruvengadam, M}, title = {Multifunctional Nanocarriers for Alzheimer's Disease: Befriending the Barriers.}, journal = {Molecular neurobiology}, volume = {61}, number = {5}, pages = {3042-3089}, pmid = {37966683}, issn = {1559-1182}, mesh = {Humans ; *Alzheimer Disease/drug therapy ; Animals ; *Drug Carriers/chemistry ; Drug Delivery Systems/methods ; Blood-Brain Barrier/metabolism/drug effects ; Nanoparticles/chemistry ; Multifunctional Nanoparticles/chemistry ; }, abstract = {Neurodegenerative diseases (NDDs) have been increasing in incidence in recent years and are now widespread worldwide. Neuronal death is defined as the progressive loss of neuronal structure or function which is closely associated with NDDs and represents the intrinsic features of such disorders. Amyotrophic lateral sclerosis, frontotemporal dementia, Alzheimer's, Parkinson's, and Huntington's diseases (AD, PD, and HD, respectively) are considered neurodegenerative diseases that affect a large number of people worldwide. Despite the testing of various drugs, there is currently no available therapy that can remedy or effectively slow the progression of these diseases. Nanomedicine has the potential to revolutionize drug delivery for the management of NDDs. The use of nanoparticles (NPs) has recently been developed to improve drug delivery efficiency and is currently subjected to extensive studies. Nanoengineered particles, known as nanodrugs, can cross the blood-brain barrier while also being less invasive compared to the most treatment strategies in use. Polymeric, magnetic, carbonic, and inorganic NPs are examples of NPs that have been developed to improve drug delivery efficiency. Primary research studies using NPs to cure AD are promising, but thorough research is needed to introduce these approaches to clinical use. In the present review, we discussed the role of metal-based NPs, polymeric nanogels, nanocarrier systems such as liposomes, solid lipid NPs, polymeric NPs, exosomes, quantum dots, dendrimers, polymersomes, carbon nanotubes, and nanofibers and surfactant-based systems for the therapy of neurodegenerative diseases. In addition, we highlighted nanoformulations such as N-butyl cyanoacrylate, poly(butyl cyanoacrylate), D-penicillamine, citrate-coated peptide, magnetic iron oxide, chitosan (CS), lipoprotein, ceria, silica, metallic nanoparticles, cholinesterase inhibitors, an acetylcholinesterase inhibitors, metal chelators, anti-amyloid, protein, and peptide-loaded NPs for the treatment of AD.}, } @article {pmid37965583, year = {2023}, author = {Oh, Y}, title = {Editorial: Cell-based neurodegenerative disease modeling.}, journal = {Frontiers in cell and developmental biology}, volume = {11}, number = {}, pages = {1323954}, doi = {10.3389/fcell.2023.1323954}, pmid = {37965583}, issn = {2296-634X}, } @article {pmid37964005, year = {2023}, author = {Lim, L and Kang, J and Song, J}, title = {Extreme diversity of 12 cations in folding ALS-linked hSOD1 unveils novel hSOD1-dependent mechanisms for Fe[2+]/Cu[2+]-induced cytotoxicity.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {19868}, pmid = {37964005}, issn = {2045-2322}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/metabolism ; Cations/chemistry/metabolism ; Copper ; Disulfides/chemistry/metabolism ; *Superoxide Dismutase-1/chemistry/genetics/metabolism ; Zinc ; Protein Folding ; }, abstract = {153-Residue copper-zinc superoxide dismutase 1 (hSOD1) is the first gene whose mutation was linked to FALS. To date, > 180 ALS-causing mutations have been identified within hSOD1, yet the underlying mechanism still remains mysterious. Mature hSOD1 is exceptionally stable constrained by a disulfide bridge to adopt a Greek-key β-barrel fold that accommodates copper/zinc cofactors. Conversely, nascent hSOD1 is unfolded and susceptible to aggregation and amyloid formation, requiring Zn[2+] to initiate folding to a coexistence of folded and unfolded states. Recent studies demonstrate mutations that disrupt Zn[2+]-binding correlate with their ability to form toxic aggregates. Therefore, to decode the role of cations in hSOD1 folding provides not only mechanistic insights, but may bear therapeutic implications for hSOD1-linked ALS. Here by NMR, we visualized the effect of 12 cations: 8 essential for humans (Na[+], K[+], Ca[2+], Zn[2+], Mg[2+], Mn[2+], Cu[2+], Fe[2+]), 3 mimicking zinc (Ni[2+], Cd[2+], Co[2+]), and environmentally abundant Al[3+]. Surprisingly, most cations, including Zn[2+]-mimics, showed negligible binding or induction for folding of nascent hSOD1. Cu[2+] exhibited extensive binding to the unfolded state but led to severe aggregation. Unexpectedly, for the first time Fe[2+] was deciphered to have Zn[2+]-like folding-inducing capacity. Zn[2+] was unable to induce folding of H80S/D83S-hSOD1, while Fe[2+] could. In contrast, Zn[2+] could trigger folding of G93A-hSOD1, but Fe[2+] failed. Notably, pre-existing Fe[2+] disrupted the Zn[2+]-induced folding of G93A-hSOD1. Comparing with the ATP-induced folded state, our findings delineate that hSOD1 maturation requires: (1) intrinsic folding capacity encoded by the sequence; (2) specific Zn[2+]-coordination; (3) disulfide formation and Cu-load catalyzed by hCCS. This study unveils a previously-unknown interplay of cations in governing the initial folding of hSOD1, emphasizing the pivotal role of Zn[2+] in hSOD1-related ALS and implying new hSOD1-dependent mechanisms for Cu[2+]/Fe[2+]-induced cytotoxicity, likely relevant to aging and other diseases.}, } @article {pmid37962258, year = {2024}, author = {Nowakowska-Kotas, M and Korbecki, A and Budrewicz, S and Bladowska, J}, title = {Investigation of cerebellar damage in adult amyotrophic lateral sclerosis patients using magnetic resonance imaging and diffusion tensor imaging.}, journal = {Advances in clinical and experimental medicine : official organ Wroclaw Medical University}, volume = {33}, number = {9}, pages = {1023-1028}, doi = {10.17219/acem/172698}, pmid = {37962258}, issn = {1899-5276}, mesh = {Humans ; Female ; Male ; Middle Aged ; *Amyotrophic Lateral Sclerosis/diagnostic imaging/pathology ; *Diffusion Tensor Imaging/methods ; Retrospective Studies ; Aged ; *Cerebellum/diagnostic imaging/pathology ; Adult ; Magnetic Resonance Imaging/methods ; }, abstract = {BACKGROUND: Research on amyotrophic lateral sclerosis (ALS) reveals that the disorder is not restricted to motor neurons.

OBJECTIVES: This neuroimaging study aimed to investigate the presence of cerebellar damage in adult ALS patients.

MATERIAL AND METHODS: The study retrospectively analyzed magnetic resonance imaging (MRI) examinations performed on a 1.5T MR unit of 33 patients (17 men and 16 women with a mean age of 59.3 years) diagnosed with ALS. Cerebellar and posterior fossa dimensions were calculated using plain MR images. In addition, diffusion tensor imaging (DTI) was used to obtain white matter integrity measurements, represented as fractional anisotropy (FA) values, in the posterior limbs of internal capsules (PLIC) and middle cerebellar peduncles (MCPs). These measurements were compared to 36 healthy volunteers (11 men and 25 women with a mean age of 55.3 years). The study also assessed clinical data for correlations with cerebellar imaging findings.

RESULTS: The linear measurements of the cerebellum did not differ between groups. However, the transverse cerebellar dimension (TCD) ratio to the maximum length of the posterior fossa (0.973 compared to 0.982, t = -2.76, p < 0.01) and FA value in both MCPs (0.67 compared to 0.65 and 0.69 compared to 0.67, p < 0.05) were significantly lower in ALS patients. No significant differences were found in FA value in the PLIC, and no significant correlations were observed between patient clinical characteristics and cerebellar damage.

CONCLUSION: This study provides evidence of cerebellar damage in adult ALS patients. These findings contribute to ALS understanding and highlight the importance of considering cerebellar involvement in the disease process. The results suggest that measuring the TCD ratio and FA value in both MCPs could be potential biomarkers for cerebellar damage in ALS patients.}, } @article {pmid37961916, year = {2023}, author = {Joilin, G and Hafezparast, M}, title = {A case for non-coding RNA as a suitable biomarker of amyotrophic lateral sclerosis.}, journal = {Expert review of molecular diagnostics}, volume = {23}, number = {12}, pages = {1049-1051}, doi = {10.1080/14737159.2023.2283522}, pmid = {37961916}, issn = {1744-8352}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/genetics ; Biomarkers ; RNA, Untranslated ; }, } @article {pmid37961424, year = {2023}, author = {Johnson, CN and Sojitra, KA and Sohn, EJ and Moreno-Romero, AK and Baudin, A and Xu, X and Mittal, J and Libich, DS}, title = {Insights into Molecular Diversity within the FET Family: Unraveling Phase Separation of the N-Terminal Low Complexity Domain from RNA-Binding Protein EWS.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {37961424}, issn = {2692-8205}, support = {R01 GM136917/GM/NIGMS NIH HHS/United States ; R01 GM140127/GM/NIGMS NIH HHS/United States ; }, abstract = {The FET family proteins, which includes FUS, EWS, and TAF15, are RNA chaperones instrumental in processes such as mRNA maturation, transcriptional regulation, and the DNA damage response. These proteins have clinical significance: chromosomal rearrangements in FET proteins are implicated in Ewing family tumors and related sarcomas. Furthermore, point mutations in FUS and TAF15 are associated with neurodegenerative conditions like amyotrophic lateral sclerosis and frontotemporal lobar dementia. The fusion protein EWS::FLI1, the causative mutation of Ewing sarcoma, arises from a genomic translocation that fuses the low-complexity domain (LCD) of EWS (EWS[LCD]) with the DNA binding domain of the ETS transcription factor FLI1. This fusion not only alters transcriptional programs but also hinders native EWS functions like splicing. However, the precise function of the intrinsically disordered EWS[LCD] is still a topic of active investigation. Due to its flexible nature, EWS[LCD] can form transient interactions with itself and other biomolecules, leading to the formation of biomolecular condensates through phase separation - a mechanism thought to be central to the oncogenicity of EWS::FLI1. In our study, we used paramagnetic relaxation enhancement NMR, analytical ultracentrifugation, light microscopy, and all-atom molecular dynamics (MD) simulations to better understand the self-association and phase separation tendencies of EWS[LCD]. Our aim was to elucidate the molecular events that underpin EWS[LCD]-mediated biomolecular condensation. Our NMR data suggest tyrosine residues primarily drive the interactions vital for EWS[LCD] phase separation. Moreover, a higher density and proximity of tyrosine residues amplify the likelihood of condensate formation. Atomistic MD simulations and hydrodynamic experiments revealed that the tyrosine-rich N and C-termini tend to populate compact conformations, establishing unique contact networks, that are connected by a predominantly extended, tyrosine-depleted, linker region. MD simulations provide critical input on the relationship between contacts formed within a single molecule (intramolecular) and inside the condensed phase (intermolecular), and changes in protein conformations upon condensation. These results offer deeper insights into the condensate-forming abilities of the FET proteins and highlights unique structural and functional nuances between EWS and its counterparts, FUS and TAF15.}, } @article {pmid37961353, year = {2023}, author = {Salaikumaran, MR and Gopal, PP}, title = {Rational Design of TDP-43 Derived α-Helical Peptide Inhibitors: an In-Silico Strategy to Prevent TDP-43 Aggregation in Neurodegenerative Disorders.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2023.10.26.564235}, pmid = {37961353}, issn = {2692-8205}, support = {R01 NS122907/NS/NINDS NIH HHS/United States ; }, abstract = {TDP-43, an essential RNA/DNA-binding protein, is central to the pathology of neurodegenerative diseases such as Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Pathological mislocalization and aggregation of TDP-43 disrupts RNA splicing, mRNA stability, and mRNA transport, thereby impairing neuronal function and survival. The formation of amyloid-like TDP-43 filaments is largely facilitated by the destabilization of an α-helical segment within the disordered C-terminal region. In this study, we hypothesized that preventing the destabilization of the α-helical domain could potentially halt the growth of these pathological filaments. To explore this, we utilized a range of in-silico techniques to design and evaluate peptide-based therapeutics. Various pathological TDP-43 amyloid-like filament crystal structures were selected for their potential to inhibit the binding of additional TDP-43 monomers to the growing filaments. Our computational approaches included biophysical and secondary structure property prediction, molecular docking, 3D structure prediction, and molecular dynamics simulations. Through these techniques, we were able to assess the structure, stability, and binding affinity of these peptides in relation to pathological TDP-43 filaments. The results of our in-silico analyses identified a selection of promising peptides, which displayed a stable α-helical structure, exhibited an increased number of intramolecular hydrogen bonds within the helical domain, and demonstrated high binding affinities for pathological TDP-43 amyloid-like filaments. Additionally, molecular dynamics simulations provided further support for the stability of these peptides, as they exhibited lower root mean square deviations in their helical propensity over 100ns. These findings establish α-helical propensity peptides as potential lead molecules for the development of novel therapeutics against TDP-43 aggregation. This structure-based computational approach for rational design of peptide inhibitors opens a new direction in the search for effective interventions for ALS, FTD, and other related neurodegenerative diseases. The peptides identified as the most promising candidates in this study are currently subject to further testing and validation through both in vitro and in vivo experiments.}, } @article {pmid37960974, year = {2023}, author = {Li, M and Liao, Y and Luo, Z and Song, H and Yang, Z}, title = {Work-related factors and risk of amyotrophic lateral sclerosis: A multivariable Mendelian randomization study.}, journal = {Brain and behavior}, volume = {13}, number = {12}, pages = {e3317}, pmid = {37960974}, issn = {2162-3279}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/epidemiology/genetics ; Genome-Wide Association Study ; Mendelian Randomization Analysis ; Smoking ; Tobacco Smoking ; Polymorphism, Single Nucleotide ; }, abstract = {BACKGROUND: The causal relationship between work-related factors and amyotrophic lateral sclerosis (ALS) is unclear. We used a Mendelian randomization (MR) analysis to investigate the unconfounded association between work-related factors and ALS.

METHODS: Univariable MR analyses were conducted to evaluate the causal effects of work-related factors on ALS. Instrumental variables from the UK Biobank on work-related factors (n = 263,615) were used as proxies. The outcome dataset used ALS (n case = 20,806, n control = 59,804) summary-level data from a large-scale genome-wide association study based on European ancestry. MR analysis used inverse variance weighted (IVW), MR-Egger, and weighted median (WM) to assess causal effects and other methods of MR for sensitivity analysis. Further multivariable MR analyses were performed to explore potential mediating effects.

RESULTS: In univariable MR, IVW methods support evidence that genetically determined job involves heavy manual or physical work (OR = 2.04, 95% CI: 1.26-3.31; p = .004) was associated with an increased risk of ALS, and the WM methods also confirm this result (OR = 2.36, 95% CI: 1.30-4.28; p = .005). No evidence of heterogeneity or horizontal pleiotropy was found in the results. In multivariable MR, the association was absent after adjusting for smoking and blood pressure.

CONCLUSIONS: Our MR analysis results demonstrate the potential causal relationship between jobs that involve heavy manual or physical work and ALS, which might be mediated by smoking and high systolic blood pressure.}, } @article {pmid37960542, year = {2023}, author = {Zhao, D and Ji, L and Yang, F}, title = {Land Cover Classification Based on Airborne Lidar Point Cloud with Possibility Method and Multi-Classifier.}, journal = {Sensors (Basel, Switzerland)}, volume = {23}, number = {21}, pages = {}, pmid = {37960542}, issn = {1424-8220}, support = {61972363//National Natural Science Foundation of China/ ; YDZJSX2021C008//Central Government Leading Local Science and Technology Development Fund Project/ ; 20221832//Postgraduate Science and Technology Project of North University of China/ ; }, abstract = {As important geospatial data, point cloud collected from an aerial laser scanner (ALS) provides three-dimensional (3D) information for the study of the distribution of typical urban land cover, which is critical in the construction of a "digital city". However, existing point cloud classification methods usually use a single machine learning classifier that experiences uncertainty in making decisions for fuzzy samples in confusing areas. This limits the improvement of classification accuracy. To take full advantage of different classifiers and reduce uncertainty, we propose a classification method based on possibility theory and multi-classifier fusion. Firstly, the feature importance measure was performed by the XGBoost algorithm to construct a feature space, and two commonly used support vector machines (SVMs) were the chosen base classifiers. Then, classification results from the two base classifiers were quantitatively evaluated to define the confusing areas in classification. Finally, the confidence degree of each classifier for different categories was calculated by the confusion matrix and normalized to obtain the weights. Then, we synthesize different classifiers based on possibility theory to achieve more accurate classification in the confusion areas. DALES datasets were utilized to assess the proposed method. The results reveal that the proposed method can significantly improve classification accuracy in confusing areas.}, } @article {pmid37960284, year = {2023}, author = {Zheng, Y and Bonfili, L and Wei, T and Eleuteri, AM}, title = {Understanding the Gut-Brain Axis and Its Therapeutic Implications for Neurodegenerative Disorders.}, journal = {Nutrients}, volume = {15}, number = {21}, pages = {}, pmid = {37960284}, issn = {2072-6643}, support = {Fondi Studenti PhD//University of Camerino/ ; }, mesh = {Humans ; Brain-Gut Axis ; *Neurodegenerative Diseases/therapy ; *Gastrointestinal Microbiome ; *Alzheimer Disease/therapy ; *Parkinson Disease/therapy ; Brain ; Dysbiosis/therapy ; }, abstract = {The gut-brain axis (GBA) is a complex bidirectional communication network connecting the gut and brain. It involves neural, immune, and endocrine communication pathways between the gastrointestinal (GI) tract and the central nervous system (CNS). Perturbations of the GBA have been reported in many neurodegenerative disorders (NDDs), such as Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS), among others, suggesting a possible role in disease pathogenesis. The gut microbiota is a pivotal component of the GBA, and alterations in its composition, known as gut dysbiosis, have been associated with GBA dysfunction and neurodegeneration. The gut microbiota might influence the homeostasis of the CNS by modulating the immune system and, more directly, regulating the production of molecules and metabolites that influence the nervous and endocrine systems, making it a potential therapeutic target. Preclinical trials manipulating microbial composition through dietary intervention, probiotic and prebiotic supplementation, and fecal microbial transplantation (FMT) have provided promising outcomes. However, its clear mechanism is not well understood, and the results are not always consistent. Here, we provide an overview of the major components and communication pathways of the GBA, as well as therapeutic approaches targeting the GBA to ameliorate NDDs.}, } @article {pmid37959385, year = {2023}, author = {Azcarate, I and Urigüen, JA and Leturiondo, M and Sandoval, CL and Redondo, K and Gutiérrez, JJ and Russell, JK and Wallmüller, P and Sterz, F and Daya, MR and Ruiz de Gauna, S}, title = {The Role of Chest Compressions on Ventilation during Advanced Cardiopulmonary Resuscitation.}, journal = {Journal of clinical medicine}, volume = {12}, number = {21}, pages = {}, pmid = {37959385}, issn = {2077-0383}, abstract = {Background: There is growing interest in the quality of manual ventilation during cardiopulmonary resuscitation (CPR), but accurate assessment of ventilation parameters remains a challenge. Waveform capnography is currently the reference for monitoring ventilation rate in intubated patients, but fails to provide information on tidal volumes and inspiration-expiration timing. Moreover, the capnogram is often distorted when chest compressions (CCs) are performed during ventilation compromising its reliability during CPR. Our main purpose was to characterize manual ventilation during CPR and to assess how CCs may impact on ventilation quality. Methods: Retrospective analysis were performed of CPR recordings fromtwo databases of adult patients in cardiac arrest including capnogram, compression depth, and airway flow, pressure and volume signals. Using automated signal processing techniques followed by manual revision, individual ventilations were identified and ventilation parameters were measured. Oscillations on the capnogram plateau during CCs were characterized, and its correlation with compression depth and airway volume was assessed. Finally, we identified events of reversed airflow caused by CCs and their effect on volume and capnogram waveform. Results: Ventilation rates were higher than the recommended 10 breaths/min in 66.7% of the cases. Variability in ventilation rates correlated with the variability in tidal volumes and other ventilatory parameters. Oscillations caused by CCs on capnograms were of high amplitude (median above 74%) and were associated with low pseudo-volumes (median 26 mL). Correlation between the amplitude of those oscillations with either the CCs depth or the generated passive volumes was low, with correlation coefficients of -0.24 and 0.40, respectively. During inspiration and expiration, reversed airflow events caused opposed movement of gases in 80% of ventilations. Conclusions: Our study confirmed lack of adherence between measured ventilation rates and the guideline recommendations, and a substantial dispersion in manual ventilation parameters during CPR. Oscillations on the capnogram plateau caused by CCs did not correlate with compression depth or associated small tidal volumes. CCs caused reversed flow during inspiration, expiration and in the interval between ventilations, sufficient to generate volume changes and causing oscillations on capnogram. Further research is warranted to assess the impact of these findings on ventilation quality during CPR.}, } @article {pmid37958929, year = {2023}, author = {Boylan, MA and Pincetic, A and Romano, G and Tatton, N and Kenkare-Mitra, S and Rosenthal, A}, title = {Targeting Progranulin as an Immuno-Neurology Therapeutic Approach.}, journal = {International journal of molecular sciences}, volume = {24}, number = {21}, pages = {}, pmid = {37958929}, issn = {1422-0067}, mesh = {Humans ; Progranulins/genetics ; Intercellular Signaling Peptides and Proteins/genetics ; *Frontotemporal Dementia/genetics ; Neurons/pathology ; *Amyotrophic Lateral Sclerosis ; }, abstract = {Immuno-neurology is an emerging therapeutic strategy for dementia and neurodegeneration designed to address immune surveillance failure in the brain. Microglia, as central nervous system (CNS)-resident myeloid cells, routinely perform surveillance of the brain and support neuronal function. Loss-of-function (LOF) mutations causing decreased levels of progranulin (PGRN), an immune regulatory protein, lead to dysfunctional microglia and are associated with multiple neurodegenerative diseases, including frontotemporal dementia caused by the progranulin gene (GRN) mutation (FTD-GRN), Alzheimer's disease (AD), Parkinson's disease (PD), limbic-predominant age-related transactivation response deoxyribonucleic acid binding protein 43 (TDP-43) encephalopathy (LATE), and amyotrophic lateral sclerosis (ALS). Immuno-neurology targets immune checkpoint-like proteins, offering the potential to convert aging and dysfunctional microglia into disease-fighting cells that counteract multiple disease pathologies, clear misfolded proteins and debris, promote myelin and synapse repair, optimize neuronal function, support astrocytes and oligodendrocytes, and maintain brain vasculature. Several clinical trials are underway to elevate PGRN levels as one strategy to modulate the function of microglia and counteract neurodegenerative changes associated with various disease states. If successful, these and other immuno-neurology drugs have the potential to revolutionize the treatment of neurodegenerative disorders by harnessing the brain's immune system and shifting it from an inflammatory/pathological state to an enhanced physiological/homeostatic state.}, } @article {pmid37958767, year = {2023}, author = {Gonzalo-Gobernado, R and Moreno-Martínez, L and González, P and Dopazo, XM and Calvo, AC and Pidal-Ladrón de Guevara, I and Seisdedos, E and Díaz-Muñoz, R and Mellström, B and Osta, R and Naranjo, JR}, title = {Repaglinide Induces ATF6 Processing and Neuroprotection in Transgenic SOD1G93A Mice.}, journal = {International journal of molecular sciences}, volume = {24}, number = {21}, pages = {}, pmid = {37958767}, issn = {1422-0067}, support = {PI21/00372//Instituto de Salud Carlos III/ ; 307//Biomedical Research Networking Center on Neurodegenerative Diseases/ ; }, mesh = {Mice ; Animals ; Mice, Transgenic ; *Amyotrophic Lateral Sclerosis/drug therapy/genetics/metabolism ; Activating Transcription Factor 6/genetics/metabolism ; Neuroprotection ; Motor Neurons/metabolism ; Kv Channel-Interacting Proteins/metabolism ; Superoxide Dismutase/genetics/metabolism ; Disease Models, Animal ; }, abstract = {The interaction of the activating transcription factor 6 (ATF6), a key effector of the unfolded protein response (UPR) in the endoplasmic reticulum, with the neuronal calcium sensor Downstream Regulatory Element Antagonist Modulator (DREAM) is a potential therapeutic target in neurodegeneration. Modulation of the ATF6-DREAM interaction with repaglinide (RP) induced neuroprotection in a model of Huntington's disease. Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder with no cure, characterized by the progressive loss of motoneurons resulting in muscle denervation, atrophy, paralysis, and death. The aim of this work was to investigate the potential therapeutic significance of DREAM as a target for intervention in ALS. We found that the expression of the DREAM protein was reduced in the spinal cord of SOD1G93A mice compared to wild-type littermates. RP treatment improved motor strength and reduced the expression of the ALS progression marker collagen type XIXα1 (Col19α1 mRNA) in the quadriceps muscle in SOD1G93A mice. Moreover, treated SOD1G93A mice showed reduced motoneuron loss and glial activation and increased ATF6 processing in the spinal cord. These results indicate that the modulation of the DREAM-ATF6 interaction ameliorates ALS symptoms in SOD1G93A mice.}, } @article {pmid37958596, year = {2023}, author = {Stoka, V and Vasiljeva, O and Nakanishi, H and Turk, V}, title = {The Role of Cysteine Protease Cathepsins B, H, C, and X/Z in Neurodegenerative Diseases and Cancer.}, journal = {International journal of molecular sciences}, volume = {24}, number = {21}, pages = {}, pmid = {37958596}, issn = {1422-0067}, support = {J1-2473, P1-0140//Slovenian Research Agency/ ; }, mesh = {Humans ; *Cysteine Proteases ; *Neurodegenerative Diseases ; Cysteine/metabolism ; Cathepsin B ; *Neoplasms ; Lysosomes/metabolism ; }, abstract = {Papain-like cysteine proteases are composed of 11 human cysteine cathepsins, originally located in the lysosomes. They exhibit broad specificity and act as endopeptidases and/or exopeptidases. Among them, only cathepsins B, H, C, and X/Z exhibit exopeptidase activity. Recently, cysteine cathepsins have been found to be present outside the lysosomes and often participate in various pathological processes. Hence, they have been considered key signalling molecules. Their potentially hazardous proteolytic activities are tightly regulated. This review aims to discuss recent advances in understanding the structural aspects of these four cathepsins, mechanisms of their zymogen activation, regulation of their activities, and functional aspects of these enzymes in neurodegeneration and cancer. Neurodegenerative effects have been evaluated, particularly in Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, multiple sclerosis, and neuropsychiatric disorders. Cysteine cathepsins also participate in tumour progression and metastasis through the overexpression and secretion of proteases, which trigger extracellular matrix degradation. To our knowledge, this is the first review to provide an in-depth analysis regarding the roles of cysteine cathepsins B, H, C, and X in neurodegenerative diseases and cancer. Further advances in understanding the functions of cysteine cathepsins in these conditions will result in the development of novel, targeted therapeutic strategies.}, } @article {pmid37957721, year = {2023}, author = {Tan, RH and McCann, H and Shepherd, CE and Pinkerton, M and Mazumder, S and Devenney, EM and Adler, GL and Rowe, DB and Kril, J and Halliday, GM and Kiernan, MC}, title = {Heterogeneity of cortical pTDP-43 inclusion morphologies in amyotrophic lateral sclerosis.}, journal = {Acta neuropathologica communications}, volume = {11}, number = {1}, pages = {180}, pmid = {37957721}, issn = {2051-5960}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/pathology ; *Frontotemporal Dementia/pathology ; DNA-Binding Proteins/genetics ; Neurons/pathology ; Phenotype ; }, abstract = {BACKGROUND: Despite the presence of significant cortical pTDP-43 inclusions of heterogeneous morphologies in patients diagnosed with amyotrophic lateral sclerosis (ALS), pathological subclassification is routinely performed in the minority of patients with concomitant frontotemporal dementia (FTD).

OBJECTIVE: In order to improve current understanding of the presence and relevance of pathological pTDP-43 subtypes in ALS, the present study examined the pattern of cortical pTDP-43 aggregates in 61 ALS cases without FTD.

RESULTS: Based on the presence, morphology and composition of pTDP-43 pathology, three distinct ALS-TDP subtypes were delineated: (1) A predominant pattern of pTDP-43 granulofilamentous neuronal inclusions (GFNIs) and grains that were immuno-negative for p62 was identified in 18% of cases designated ALS-TDP type E; (2) neuronal cytoplasmic inclusions (NCIs) that were immuno-positive for both pTDP-43 and p62 were observed in 67% of cases assigned ALS-TDP type B; and (3) scarce cortical pTDP-43 and p62 aggregates were identified in 15% of cases coined ALS-TDP type SC (scarce cortical). Quantitative analyses revealed a significantly greater burden of pTDP-43 GFNI and grains in ALS-TDP type E. Principal component analysis demonstrated significant relationships between GFNIs, grains and ALS-TDP subtypes to support the distinction of subtypes E and B. No significant difference in age at death or disease duration was found between ALS-TDP subgroups to suggest that these subtypes represent earlier or later stages of the same disease process. Instead, a significantly higher ALS-TDP stage, indicating greater topographical spread of pTDP-43, was identified in ALS-TDP type E. Alzheimer's disease neuropathological change (ABC score ≥ intermediate) and Lewy body disease (Braak stage ≥ IV) was more prevalent in the ALS-TDP type SC cohort, which also demonstrated a significantly lower overall cognitive score.

CONCLUSION: In summary, the present study demonstrates that ALS-TDP does not represent a single homogenous neuropathology. We propose the subclassification of ALS-TDP into three distinct subtypes using standard immuno-stains for pTDP-43 and p62 in the motor cortex, which is routinely sampled and evaluated for diagnostic neuropathological characterisation of ALS. We propose that future studies specify both clinicopathological group and pTDP-43 subtype to advance current understanding of the pathogenesis of clinical phenotypes in pTDP-43 proteinopathies, which will have significant relevance to the development of targeted therapies for this heterogeneous disorder.}, } @article {pmid37955773, year = {2023}, author = {Colasuonno, F and Price, R and Moreno, S}, title = {Upper and Lower Motor Neurons and the Skeletal Muscle: Implication for Amyotrophic Lateral Sclerosis (ALS).}, journal = {Advances in anatomy, embryology, and cell biology}, volume = {236}, number = {}, pages = {111-129}, pmid = {37955773}, issn = {0301-5556}, mesh = {Animals ; Mice ; *Amyotrophic Lateral Sclerosis ; Motor Neurons ; Muscle, Skeletal ; Neurons, Efferent ; *Nerve Tissue ; }, abstract = {The relationships between motor neurons and the skeletal muscle during development and in pathologic contexts are addressed in this Chapter.We discuss the developmental interplay of muscle and nervous tissue, through neurotrophins and the activation of differentiation and survival pathways. After a brief overview on muscular regulatory factors, we focus on the contribution of muscle to early and late neurodevelopment. Such a role seems especially intriguing in relation to the epigenetic shaping of developing motor neuron fate choices. In this context, emphasis is attributed to factors regulating energy metabolism, which may concomitantly act in muscle and neural cells, being involved in common pathways.We then review the main features of motor neuron diseases, addressing the cellular processes underlying clinical symptoms. The involvement of different muscle-associated neurotrophic factors for survival of lateral motor column neurons, innervating MyoD-dependent limb muscles, and of medial motor column neurons, innervating Myf5-dependent back musculature is discussed. Among the pathogenic mechanisms, we focus on oxidative stress, that represents a common and early trait in several neurodegenerative disorders. The role of organelles primarily involved in reactive oxygen species scavenging and, more generally, in energy metabolism-namely mitochondria and peroxisomes-is discussed in the frame of motor neuron degeneration.We finally address muscular involvement in amyotrophic lateral sclerosis (ALS), a multifactorial degenerative disorder, hallmarked by severe weight loss, caused by imbalanced lipid metabolism. Even though multiple mechanisms have been recognized to play a role in the disease, current literature generally assumes that the primum movens is neuronal degeneration and that muscle atrophy is only a consequence of such pathogenic event. However, several lines of evidence point to the muscle as primarily involved in the disease, mainly through its role in energy homeostasis. Data from different ALS mouse models strongly argue for an early mitochondrial dysfunction in muscle tissue, possibly leading to motor neuron disturbances. Detailed understanding of skeletal muscle contribution to ALS pathogenesis will likely lead to the identification of novel therapeutic strategies.}, } @article {pmid37955564, year = {2024}, author = {Pinto, S and Oliveira Santos, M and Gromicho, M and Swash, M and de Carvalho, M}, title = {Impact of diabetes mellitus on the respiratory function of amyotrophic lateral sclerosis patients.}, journal = {European journal of neurology}, volume = {31}, number = {2}, pages = {e16129}, pmid = {37955564}, issn = {1468-1331}, support = {GA101017598//European Union's Horizon 2020 research and innovation program/ ; }, mesh = {Male ; Humans ; Middle Aged ; Aged ; *Amyotrophic Lateral Sclerosis ; Retrospective Studies ; *Respiratory Insufficiency/complications ; Respiratory Function Tests/adverse effects ; *Diabetes Mellitus ; }, abstract = {BACKGROUND AND PURPOSE: Respiratory insufficiency and its complications are the main cause of death in amyotrophic lateral sclerosis (ALS). The impact of diabetes mellitus (DM) on respiratory function of ALS patients is uncertain.

METHODS: A retrospective cohort study was carried out. From the 1710 patients with motor neuron disease followed in our unit, ALS and progressive muscular atrophy patients were included. We recorded demographic characteristics, functional ALS rating scale (Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised [ALSFRS-R]) and its subscores at first visit, respiratory function tests, arterial blood gases, phrenic nerve amplitude (PhrenAmpl), and mean nocturnal oxygen saturation (SpO2 mean). We excluded patients with other relevant diseases. Two subgroups were analysed: DIAB (patients with DM) and noDIAB (patients without DM). Independent t-test, χ[2] , or Fisher exact test was applied. Binomial logistic regression analyses assessed DM effects. Kaplan-Meier analysis assessed survival. p < 0.05 was considered significant.

RESULTS: We included 1639 patients (922 men, mean onset age = 62.5 ± 12.6 years, mean disease duration = 18.1 ± 22.0 months). Mean survival was 43.3 ± 40.7 months. More men had DM (p = 0.021). Disease duration was similar between groups (p = 0.063). Time to noninvasive ventilation (NIV) was shorter in DIAB (p = 0.004); total survival was similar. No differences were seen for ALSFRS-R or its decay rate. At entry, DIAB patients were older (p < 0.001), with lower forced vital capacity (p = 0.001), arterial oxygen pressure (p = 0.01), PhrenAmpl (p < 0.001), and SpO2 mean (p = 0.014).

CONCLUSIONS: ALS patients with DM had increased risk of respiratory impairment and should be closely monitored. Early NIV allowed for similar survival rate between groups.}, } @article {pmid37955299, year = {2023}, author = {Yuan, YH and Mao, ND and Duan, JL and Zhang, H and Garrido, C and Lirussi, F and Gao, Y and Xie, T and Ye, XY}, title = {Recent progress in discovery of novel AAK1 inhibitors: from pain therapy to potential anti-viral agents.}, journal = {Journal of enzyme inhibition and medicinal chemistry}, volume = {38}, number = {1}, pages = {2279906}, pmid = {37955299}, issn = {1475-6374}, mesh = {Humans ; *Protein Serine-Threonine Kinases ; *Antiviral Agents/pharmacology ; Phosphorylation ; Pain ; }, abstract = {Adaptor associated kinase 1 (AAK1), a member of the Ark1/Prk1 family of Ser/Thr kinases, is a specific key kinase regulating Thr156 phosphorylation at the μ2 subunit of the adapter complex-2 (AP-2) protein. Due to their important biological functions, AAK1 systems have been validated in clinics for neuropathic pain therapy, and are being explored as potential therapeutic targets for diseases caused by various viruses such as Hepatitis C (HCV), Dengue, Ebola, and COVID-19 viruses and for amyotrophic lateral sclerosis (ALS). Centreing on the advances of drug discovery programs in this field up to 2023, AAK1 inhibitors are discussed from the aspects of the structure-based rational molecular design, pharmacology, toxicology and synthetic routes for the compounds of interest in this review. The aim is to provide the medicinal chemistry community with up-to-date information and to accelerate the drug discovery programs in the field of AAK1 small molecule inhibitors.}, } @article {pmid37955056, year = {2024}, author = {Spörndly-Nees, S and Jakobsson Larsson, B and Zetterberg, L and Åkerblom, Y and Nyholm, D and Åsenlöf, P}, title = {Pain in patients with motor neuron disease: Variation of pain and association with disease severity, health-related quality of life and depression - A longitudinal study.}, journal = {Palliative & supportive care}, volume = {22}, number = {5}, pages = {1150-1157}, doi = {10.1017/S1478951523001347}, pmid = {37955056}, issn = {1478-9523}, mesh = {Humans ; Female ; Male ; *Quality of Life/psychology ; Middle Aged ; Longitudinal Studies ; *Depression/psychology/etiology/complications ; Aged ; *Motor Neuron Disease/complications/psychology ; Prospective Studies ; *Pain/psychology/etiology/complications ; Severity of Illness Index ; Surveys and Questionnaires ; Pain Measurement/methods ; Adult ; Cohort Studies ; Disease Progression ; Psychometrics/methods/instrumentation ; }, abstract = {OBJECTIVES: To describe levels of pain over time during disease progression in individual patients and for a total sample of patients with motor neuron disease (MND), respectively, and to examine associations between pain, disease severity, health-related quality of life (HRQOL), and depression.

METHODS: A prospective cohort study was conducted on 68 patients with MND, including data collected on five occasions over a period of 2 years. Pain was assessed using the Brief Pain Inventory - Short Form. Depression was assessed using the Amyotrophic Lateral Sclerosis (ALS)-Depression-Inventory (ADI-12). Disability progression was measured using the Amyotrophic Lateral Sclerosis Functional Rating Scale - Revised Version (ALSFRS-R). HRQOL was assessed using the Amyotrophic Lateral Sclerosis Assessment Questionnaire (ALSAQ-5).

RESULTS: Participants reported great individual variation over time. The median level of pain was 4 (min 0 and max 10). Higher levels of pain during the last 24 h were associated with higher depression scores (ADI-12), poorer quality of life (ALSAQ-5), and lower reporting of fine and gross motor skills (ALSFRS-R). Baseline pain levels did not predict future values of depression and function. Individuals reporting average pain >3 experienced more hopelessness toward the future and reported higher depression scores compared with participants reporting average pain <3.

SIGNIFICANCE OF RESULTS: Great within-individual variation of pain intensity was reported. Pain intensity was associated with depression, function and HRQOL cross-sectionally, but it did not have a strong prognostic value for future depression, function, or HRQOL. Patients with MND should be offered frequent assessment of pain and depressive symptoms in person-centered care, allowing for individualization of treatment.}, } @article {pmid37954904, year = {2023}, author = {Zhao, K and Chen, P and Alexander-Bloch, A and Wei, Y and Dyrba, M and Yang, F and Kang, X and Wang, D and Fan, D and Ye, S and Tang, Y and Yao, H and Zhou, B and Lu, J and Yu, C and Wang, P and Liao, Z and Chen, Y and Huang, L and Zhang, X and Han, Y and Li, S and Liu, Y}, title = {A neuroimaging biomarker for Individual Brain-Related Abnormalities In Neurodegeneration (IBRAIN): a cross-sectional study.}, journal = {EClinicalMedicine}, volume = {65}, number = {}, pages = {102276}, pmid = {37954904}, issn = {2589-5370}, abstract = {BACKGROUND: Alzheimer's disease (AD) is a prevalent neurodegenerative disorder that poses a worldwide public health challenge. A neuroimaging biomarker would significantly improve early diagnosis and intervention, ultimately enhancing the quality of life for affected individuals and reducing the burden on healthcare systems.

METHODS: Cross-sectional and longitudinal data (10,099 participants with 13,380 scans) from 12 independent datasets were used in the present study (this study was performed between September 1, 2021 and February 15, 2023). The Individual Brain-Related Abnormalities In Neurodegeneration (IBRAIN) score was developed via integrated regional- and network-based measures under an ensemble machine learning model based on structural MRI data. We systematically assessed whether IBRAIN could be a neuroimaging biomarker for AD.

FINDINGS: IBRAIN accurately differentiated individuals with AD from NCs (AUC = 0.92) and other neurodegenerative diseases, including Frontotemporal dementia (FTD), Parkinson's disease (PD), Vascular dementia (VaD) and Amyotrophic Lateral Sclerosis (ALS) (AUC = 0.92). IBRAIN was significantly correlated to clinical measures and gene expression, enriched in immune process and protein metabolism. The IBRAIN score exhibited a significant ability to reveal the distinct progression of prodromal AD (i.e., Mild cognitive impairment, MCI) (Hazard Ratio (HR) = 6.52 [95% CI: 4.42∼9.62], p < 1 × 10[-16]), which offers similar powerful performance with Cerebrospinal Fluid (CSF) Aβ (HR = 3.78 [95% CI: 2.63∼5.43], p = 2.13 × 10[-14]) and CSF Tau (HR = 3.77 [95% CI: 2.64∼5.39], p = 9.53 × 10[-15]) based on the COX and Log-rank test. Notably, the IBRAIN shows comparable sensitivity (beta = -0.70, p < 1 × 10[-16]) in capturing longitudinal changes in individuals with conversion to AD than CSF Aβ (beta = -0.26, p = 4.40 × 10[-9]) and CSF Tau (beta = 0.12, p = 1.02 × 10[-5]).

INTERPRETATION: Our findings suggested that IBRAIN is a biologically relevant, specific, and sensitive neuroimaging biomarker that can serve as a clinical measure to uncover prodromal AD progression. It has strong potential for application in future clinical practice and treatment trials.

FUNDING: Science and Technology Innovation 2030 Major Projects, the National Natural Science Foundation of China, Beijing Natural Science Funds, the Fundamental Research Funds for the CentralUniversity, and the Startup Funds for Talents at Beijing Normal University.}, } @article {pmid37954145, year = {2023}, author = {Kalia, M and Miotto, M and Ness, D and Opie-Martin, S and Spargo, TP and Di Rienzo, L and Biagini, T and Petrizzelli, F and Al Khleifat, A and Kabiljo, R and , and , and Mazza, T and Ruocco, G and Milanetti, E and Dobson, RJ and Al-Chalabi, A and Iacoangeli, A}, title = {Molecular dynamics analysis of superoxide dismutase 1 mutations suggests decoupling between mechanisms underlying ALS onset and progression.}, journal = {Computational and structural biotechnology journal}, volume = {21}, number = {}, pages = {5296-5308}, pmid = {37954145}, issn = {2001-0370}, abstract = {Mutations in the superoxide dismutase 1 (SOD1) gene are the second most common known cause of ALS. SOD1 variants express high phenotypic variability and over 200 have been reported in people with ALS. It was previously proposed that variants can be broadly classified in two groups, 'wild-type like' (WTL) and 'metal binding region' (MBR) variants, based on their structural location and biophysical properties. MBR variants, but not WTL variants, were associated with a reduction of SOD1 enzymatic activity. In this study we used molecular dynamics and large clinical datasets to characterise the differences in the structural and dynamic behaviour of WTL and MBR variants with respect to the wild-type SOD1, and how such differences influence the ALS clinical phenotype. Our study identified marked structural differences, some of which are observed in both variant groups, while others are group specific. Moreover, collecting clinical data of approximately 500 SOD1 ALS patients carrying variants, we showed that the survival time of patients carrying an MBR variant is generally longer (∼6 years median difference, p < 0.001) with respect to patients with a WTL variant. In conclusion, our study highlighted key differences in the dynamic behaviour between WTL and MBR SOD1 variants, and between variants and wild-type SOD1 at an atomic and molecular level, that could be further investigated to explain the associated phenotypic variability. Our results support the hypothesis of a decoupling between mechanisms of onset and progression of SOD1 ALS, and an involvement of loss-of-function of SOD1 with the disease progression.}, } @article {pmid37953591, year = {2023}, author = {Benlefki, S and Younes, R and Challuau, D and Bernard-Marissal, N and Hilaire, C and Scamps, F and Bowerman, M and Kothary, R and Schneider, BL and Raoul, C}, title = {Differential effect of Fas activation on spinal muscular atrophy motoneuron death and induction of axonal growth.}, journal = {Cellular and molecular biology (Noisy-le-Grand, France)}, volume = {69}, number = {10}, pages = {1-8}, doi = {10.14715/cmb/2023.69.10.1}, pmid = {37953591}, issn = {1165-158X}, mesh = {Humans ; Mice ; Animals ; *Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology ; Mice, Transgenic ; Motor Neurons/metabolism/pathology ; *Muscular Atrophy, Spinal/genetics/metabolism/pathology ; Axons/pathology ; }, abstract = {Amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA) are the most common motoneuron diseases affecting adults and infants, respectively. ALS and SMA are both characterized by the selective degeneration of motoneurons. Although different in their genetic etiology, growing evidence indicates that they share molecular and cellular pathogenic signatures that constitute potential common therapeutic targets. We previously described a motoneuron-specific death pathway elicited by the Fas death receptor, whereby vulnerable ALS motoneurons show an exacerbated sensitivity to Fas activation. However, the mechanisms that drive the loss of SMA motoneurons remains poorly understood. Here, we describe an in vitro model of SMA-associated degeneration using primary motoneurons derived from Smn2B/- SMA mice and show that Fas activation selectively triggers death of the proximal motoneurons. Fas-induced death of SMA motoneurons has the molecular signature of the motoneuron-selective Fas death pathway that requires activation of p38 kinase, caspase-8, -9 and -3 as well as upregulation of collapsin response mediator protein 4 (CRMP4). In addition, Rho-associated Kinase (ROCK) is required for Fas recruitment. Remarkably, we found that exogenous activation of Fas also promotes axonal elongation in both wildtype and SMA motoneurons. Axon outgrowth of motoneurons promoted by Fas requires the activity of ERK, ROCK and caspases. This work defines a dual role of Fas signaling in motoneurons that can elicit distinct responses from cell death to axonal growth.}, } @article {pmid37953075, year = {2023}, author = {Shimizu, H and Nishimura, Y and Shiide, Y and Akimoto, M and Yashiro, M and Ueda, M and Hirai, M and Yoshino, H and Mizutani, T and Kanai, K and Kano, O and Kimura, H and Sekino, H and Ito, K}, title = {Pharmacokinetics of Edaravone Oral Suspension in Patients With Amyotrophic Lateral Sclerosis.}, journal = {Clinical therapeutics}, volume = {45}, number = {12}, pages = {1251-1258}, doi = {10.1016/j.clinthera.2023.09.025}, pmid = {37953075}, issn = {1879-114X}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy ; Edaravone/pharmacokinetics ; Glucuronides/therapeutic use ; *Neuroprotective Agents/pharmacokinetics ; Sulfates/therapeutic use ; }, abstract = {PURPOSE: Edaravone is a neuroprotective agent approved as an intravenous treatment for amyotrophic lateral sclerosis (ALS). The intravenous administration of edaravone places a burden on patients and there is a clinical need for oral agents for the treatment of ALS. This report aimed to assess the pharmacokinetics and safety of an edaravone oral suspension in patients with ALS after oral and percutaneous endoscopic gastrostomy (PEG) tube administration.

METHODS: Two single-dose, open-label phase 1 clinical studies were conducted. Edaravone oral suspension (105 mg of edaravone in 5 mL aqueous suspension) was administered orally and via PEG tube to 9 and 6 Japanese patients with ALS, respectively. Plasma and urinary pharmacokinetics of unchanged edaravone and its metabolites (sulfate and glucuronide conjugates) were determined. Safety was also evaluated.

FINDINGS: After reaching maximum plasma concentration, the mean plasma concentration-time of unchanged edaravone showed a triphasic elimination. Mean plasma concentration-time profiles of the metabolites were higher than those of unchanged edaravone. The mean urinary excretion ratios were higher for the glucuronide conjugate than for either unchanged edaravone or the sulfate conjugate. In patients administered edaravone orally, a single adverse event occurred (blood urine present), which was mild and improved without medical intervention. No adverse drug reactions or serious adverse events were reported. In patients administered edaravone via PEG tube, 5 treatment-emergent adverse events were reported in 3 patients; none were related to the study drug. No adverse drug reactions were reported.

IMPLICATIONS: In patients with ALS, a single dose of edaravone oral suspension was well absorbed and mainly eliminated in urine as the glucuronide conjugate. No safety concerns emerged. Pharmacokinetics were similar to those previously reported in healthy participants following oral administration. This indicates that effective drug concentrations were achieved and edaravone can be successfully administered both orally and via a PEG tube in patients with ALS.

CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT04176224 (oral administration) and NCT04254913 (PEG tube administration), www.

CLINICALTRIALS: gov.}, } @article {pmid37952981, year = {2023}, author = {Okano, H and Morimoto, S and Kato, C and Nakahara, J and Takahashi, S}, title = {Induced pluripotent stem cells-based disease modeling, drug screening, clinical trials, and reverse translational research for amyotrophic lateral sclerosis.}, journal = {Journal of neurochemistry}, volume = {167}, number = {5}, pages = {603-614}, doi = {10.1111/jnc.16005}, pmid = {37952981}, issn = {1471-4159}, support = {JP21wm0425009//Japan Agency for Medical Research and Development/ ; JP22bm0804003//Japan Agency for Medical Research and Development/ ; JP22ek0109616//Japan Agency for Medical Research and Development/ ; JP23bm1423002//Japan Agency for Medical Research and Development/ ; JP23bm1123046//Japan Agency for Medical Research and Development/ ; JP23kk0305024//Japan Agency for Medical Research and Development/ ; JP20H00485//Japan Society for the Promotion of Science/ ; JP21H05278//Japan Society for the Promotion of Science/ ; JP22K15736//Japan Society for the Promotion of Science/ ; JP22K07500//Japan Society for the Promotion of Science/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism ; *Induced Pluripotent Stem Cells/metabolism ; Drug Evaluation, Preclinical ; *Neurodegenerative Diseases/metabolism ; Translational Research, Biomedical ; Randomized Controlled Trials as Topic ; }, abstract = {It has been more than 10 years since the hopes for disease modeling and drug discovery using induced pluripotent stem cell (iPSC) technology boomed. Recently, clinical trials have been conducted with drugs identified using this technology, and some promising results have been reported. For amyotrophic lateral sclerosis (ALS), a devastating neurodegenerative disease, several groups have identified candidate drugs, ezogabine (retigabine), bosutinib, and ropinirole, using iPSCs-based drug discovery, and clinical trials using these drugs have been conducted, yielding interesting results. In our previous study, an iPSCs-based drug repurposing approach was utilized to show the potential of ropinirole hydrochloride (ROPI) in reducing ALS-specific pathological phenotypes. Recently, a phase 1/2a trial was conducted to investigate the effects of ropinirole on ALS further. This double-blind, randomized, placebo-controlled study confirmed the safety and tolerability of and provided evidence of its ability to delay disease progression and prolong the time to respiratory failure in ALS patients. Furthermore, in the reverse translational research, in vitro characterization of patient-derived iPSCs-motor neurons (MNs) mimicked the therapeutic effects of ROPI in vivo, suggesting the potential application of this technology to the precision medicine of ALS. Interestingly, RNA-seq data showed that ROPI treatment suppressed the sterol regulatory element-binding protein 2-dependent cholesterol biosynthesis pathway. Therefore, this pathway may be involved in the therapeutic effect of ROPI on ALS. The possibility that this pathway may be involved in the therapeutic effect of ALS was demonstrated. Finally, new future strategies for ALS using iPSCs technology will be discussed in this paper.}, } @article {pmid37952517, year = {2024}, author = {Zürcher, BF}, title = {The Tibetan Formula Cong zhi 6 in the ORL (ENT) Practice: Experiences with Laryngopharyngeal Reflux.}, journal = {Complementary medicine research}, volume = {31}, number = {1}, pages = {84-88}, doi = {10.1159/000534212}, pmid = {37952517}, issn = {2504-2106}, mesh = {Humans ; *Laryngopharyngeal Reflux/drug therapy ; Retrospective Studies ; Pepsin A ; Tibet ; Europe ; }, abstract = {BACKGROUND: Laryngopharyngeal reflux (LPR) is a frequent condition; in European countries, the prevalence can be estimated as 10-30% of the general population. Treatment includes lifestyle measures and highly dosed proton pump inhibitors (PPIs) over at least 4 weeks. However, PPIs are not unproblematic due to their potential side effects and the known phenomenon of rebound acid hypersecretion. Cong zhi 6 is a multi-herbal Tibetan formula additionally containing calcium carbonate and is available in several European countries as a food supplement Padma Aciben/Padma AciTib.

CASE REPORT: Ten patients with LPR took Cong zhi 6. The course of the complaints was documented, and the data were retrospectively analysed. Clinical symptoms as assessed with the Reflux Symptom Index (RSI) questionnaire and the findings in laryngoscopy with the Reflux Finding Score (RFS) both showed marked improvement of several symptoms. The number of patients with pathological LPR sum score was significantly reduced from 8 to 2 patients and from 10 to 1 patient in RSI and RFS, respectively. The mean sum scores were reduced from 18.1 to 8.4 (RSI) and from 12.9 to 4.4 (RFS), respectively. Also, other gastrointestinal symptoms, such as abdominal pain, bloating, feeling of fullness, and nausea, which are usually associated with functional dyspepsia and irritable bowel syndrome, were markedly improved (reduction of mean score of the 3 most frequent symptoms by 77-87%).

CONCLUSION: Standard medical treatment for LPR consists in high dosed PPI for at least 4 weeks, which is known for several side effects and does not treat reliable the nonacid component of LPR of pepsin or other gastric enzymes. Therefore, other medical treatment options are urgently needed. The promising data of this case series suggest that the Tibetan herbal formula Cong zhi 6 may be a treatment option in LPR and related gastrointestinal symptoms and warrant further research.

UNLABELLED: HintergrundDer laryngopharyngeale Reflux (LPR) ist eine häufige Erkrankung. In europäischen Ländern wird die Prävalenz in der Gesamtbevölkerung auf 10–30% geschätzt. Die Behandlung beinhaltet Ernährungs- und Verhaltensänderung sowie die Gabe hochdosierter Protonen-Pumpen-Hemmer (PPI) über mindestens 4 Wochen. PPI sind jedoch aufgrund ihrer hohen potenziellen Nebenwirkungen und des bekannten Rebound-Phänomens der sauren Magensafthypersekretion nicht unproblematisch. Cong zhi 6 ist eine tibetische Rezeptur aus einem Vielpflanzengemisch sowie zusätzlich Calciumcarbonat und ist in einigen europäischen Ländern als Nahrungsergänzungsmittel Padma Aciben/Padma AciTib erhältlich.Case ReportZehn Patienten mit laryngo-pharyngealem Reflux (LPR) nahmen Cong zhi 6 ein. Der Beschwerdeverlauf wurde dokumentiert und die Daten retrospektiv analysiert. Die klinischen Symptome, die mithilfe des Reflux Symptom Index (RSI) Fragebogens erfasst wurden und die mittels des Reflux Finding Score (RFS) beurteilten laryngoskopischen Befunde zeigten beide eine deutliche Verbesserung verschiedener Symptome. Die Zahl der Patienten mit pathologischen LPR-Summenscore reduzierte sich signifikant, im RSI von 8 auf 2 und im RFS von 10 auf 1 Patienten. Der mittlere Summenwert sank von 18.1 auf 8.4 (RSI) und von 12.9 auf 4.4 (RFS). Des Weiteren zeigte sich auch bei anderen gastrointestinalen Beschwerden, wie Bauchschmerzen, Blähungen, Völlegefühl und Übelkeit, die normalerweise mit funktioneller Dyspepsie oder Reizdarm zusammenhängen, eine deutliche Verbesserung (durchschnittliche Verringerung des Scores der drei häufigsten Symptome um 77–87%).ZusammenfassungDie medikamentöse Standardbehandlung bei LPR besteht aus der hochdosierten PPI-Gabe über mindestens 4 Wochen, die jedoch für verschiedene Nebenwirkungen bekannt ist und die nicht-saure Komponente von LPR, wie Pepsin oder andere digestive Enzyme, nicht mitbehandelt. Daher sind andere medikamentöse Behandlungsmöglichkeiten dringend erforderlich. Die vielversprechenden Daten dieser Fallserie deuten darauf hin, dass die tibetische Pflanzenrezeptur Cong zhi 6 eine Behandlungsoption bei LPR sowie deren gastrointestinalen Symptome darstellt und rechtfertigen weitere Studien.}, } @article {pmid37952511, year = {2023}, author = {Zhang, X and Qu, X and Zou, Y}, title = {The Effect of Astragalus on Humoral and Cellular Immune Response: A Systematic Review and Meta-Analysis of Human Studies.}, journal = {Complementary medicine research}, volume = {30}, number = {6}, pages = {535-543}, doi = {10.1159/000534826}, pmid = {37952511}, issn = {2504-2106}, mesh = {Humans ; *Interleukin-10 ; *Interleukin-2 ; Interleukin-4 ; Interleukin-6 ; Tumor Necrosis Factor-alpha ; Biomarkers ; }, abstract = {INTRODUCTION: Astragalus is used in traditional Chinese medicine for immune system disorders. Its effect on immune system function is evaluated in multiple studies. The objective of this systematic review and meta-analysis was to evaluate the effect of Astragalus on humoral and cellular immune response in human studies.

METHODS: A comprehensive search of electronic databases was conducted to identify relevant studies published up to April 2023. Studies that assessed the impact of Astragalus on humoral and cellular immune markers were included. The data were extracted, and a random-effects meta-analysis was performed to determine the overall effect size. Subgroup analyses were conducted based on outcome measures.

RESULTS: A total of 19 studies, including 1,094 human participants, were included in the meta-analysis. The analysis of humoral immune markers revealed a significant reduction in proinflammatory cytokines, including IL-2, IL-4, IL-6, IL-10, TNF-α, and IFN-γ, following Astragalus intervention (SMD -2.8765, 95% CI: -3.2385 to -2.5145, p < 0.0001). In the cellular immunity domain, Astragalus was found to significantly increase CD3 levels and the CD4/CD8 ratio (SMD 2.4629, 95% CI: 1.9598; 2.9661). Subgroup analyses based on outcome measures supported these findings. However, substantial heterogeneity was observed among the included studies.

CONCLUSION: This systematic review and meta-analysis provide evidence supporting the immunomodulatory effects of Astragalus on humoral and cellular response. Astragalus demonstrated a significant reduction in proinflammatory cytokines and an enhancement of cellular immune markers, suggesting its potential as a therapeutic agent for immune-related disorders.

UNLABELLED: EinleitungAstragalus wird in der traditionellen chinesischen Medizin bei Erkrankungen des Immunsystems eingesetzt. Seine Wirkung auf das Immunsystem ist in mehreren Studien untersucht worden. Das Ziel dieser systematischen Übersichtsarbeit und Metaanalyse ist es, die Wirkung von Astragalus auf die humorale und zelluläre Immunantwort in Studien am Menschen zu untersuchen.MethodenEine umfassende Suche in elektronischen Datenbanken wurde durchgeführt, um einschlägige Studien zu finden, die bis April 2023 veröffentlicht wurden. Eingeschlossen wurden Studien, die die Auswirkung von Astragalus auf Marker der humoralen und zellulären Immunantwort untersuchten. Die Daten wurden extrahiert und eine Random-Effects-Metaanalyse durchgeführt, um die Gesamt-Effektstärke zu ermitteln. Subgruppenanalysen wurden basierend auf Zielgrößen durchgeführt.ErgebnisseInsgesamt 19 Studien mit 1’094 menschlichen Teilnehmern wurden in die Metaanalyse eingeschlossen. Die Analyse der humoralen Immunmarker ergab eine signifikante Abnahme proinflammatorischer Zytokine, darunter IL-2, IL-4, IL-6, IL-10, TNF-α und IFN-γ, nach Anwendung von Astragalus (SMD –2.8765; 95%-KI: −3.2385, −2.5145; p < 0.0001). Bei der zellulären Immunität zeigte Astralagus eine signifikante Erhöhung der CD3-Konzentration und des CD4/CD8-Quotienten (SMD 2.4629; 95%-KI: 1.9598, 2.9661). Die Subgruppenanalysen nach Zielgrößen bestätigten diese Ergebnisse. Zwischen den eingeschlossenen Studien bestand jedoch erhebliche Heterogenität.SchlussfolgerungDiese systematische Übersichtsarbeit und Metaanalyse liefert Belege für die immunmodulatorischen Effekte von Astragalus auf die humorale und zelluläre Immunantwort. Astragalus zeigte eine signifikante Abnahme proinflammatorischer Zytokine und eine Verbesserung von Markern der zellulären Immunität, was auf sein Potenzial als Therapeutikum bei immunvermittelten Störungen hindeutet.}, } @article {pmid37952009, year = {2024}, author = {Hu, N and Zhang, L and Shen, D and Yang, X and Liu, M and Cui, L}, title = {Incidence of amyotrophic lateral sclerosis-associated genetic variants: a clinic-based study.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {45}, number = {4}, pages = {1515-1522}, pmid = {37952009}, issn = {1590-3478}, support = {XDB39040000//The Strategic Priority Research Program (Pilot study)"Biological basis of aging and therapeutic strategies" of the Chinese Academy of Sciences/ ; CIFMS 2021-I2M-1-003//CAMS Innovation Fund for Medical Sciences/ ; 2022-PUMCH-B-017//National High Level Hospital Clinical Research Funding/ ; 7202158//Natural Science Foundation of Beijing Municipality/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/epidemiology/genetics ; Incidence ; *Cerebellar Ataxia ; Mutation ; }, abstract = {OBJECTIVE: This study is to determine the incidence of genetic forms of amyotrophic lateral sclerosis (ALS) in clinic-based population.

METHODS: Next-generation sequencing (NGS) of whole exome sequencing (WES) was conducted among a total of 374 patients with definite or probable ALS to identify ALS-associated genes based on ALSoD database (https://alsod.ac.uk) [2023-07-01].

RESULTS: Variants of ALS-associated genes were detected in 54.01% (202/374) ALS patients, among which 8.29% (31/374) were pathogenic/likely pathogenic (P/LP). The detection rates of P/LP variants were significantly higher in familial ALS than sporadic ALS (42.31% vs 5.75%, p < 0.001), while VUS mutations were more commonly detected in sporadic ALS (23.07% vs 47.13%, p = 0.018). There is no significant difference in detection rate between patients with and without early onset (8.93% vs 7.77%), rapid progression (9.30% vs 8.91%), cognitive decline (15.00% vs 7.93%), and cerebellar ataxia (20.00% vs 8.15%) (p > 0.05).

CONCLUSION: Over half of our ALS patients carried variants of ALS-related genes, most of which were variants of uncertain significance (VUS). Family history of ALS could work as strong evidence for carrying P/LP variants regarding ALS. There was no additionally suggestive effect of indicators including early onset, progression rate, cognitive decline, or cerebellar ataxia on the recommendation of genetic testing in clinical practice.}, } @article {pmid37951279, year = {2024}, author = {Vu Trung, K and Heise, C and Abou-Ali, E and Auriemma, F and Karam, E and van der Wiel, SE and Bruno, MJ and Caillol, F and Giovannini, M and Masaryk, V and Will, U and Anderloni, A and Pérez-Cuadrado-Robles, E and Dugic, A and Meier, B and Paik, WH and Petrone, MC and Wichmann, D and Dinis-Ribeiro, M and Gonçalves, TC and Wedi, E and Schmidt, A and Gulla, A and Hoffmeister, A and Rosendahl, J and Ratone, JP and Saadeh, R and Repici, A and Deprez, P and Sauvanet, A and Souche, FR and Fabre, JM and Muehldorfer, S and Caca, K and Löhr, M and Michl, P and Krug, S and Regner, S and Gaujoux, S and Hollenbach, M}, title = {Endoscopic papillectomy for ampullary lesions of minor papilla.}, journal = {Gastrointestinal endoscopy}, volume = {99}, number = {4}, pages = {587-595.e1}, doi = {10.1016/j.gie.2023.10.040}, pmid = {37951279}, issn = {1097-6779}, mesh = {Humans ; Treatment Outcome ; *Ampulla of Vater/surgery/pathology ; Endoscopy, Gastrointestinal ; Pancreatic Ducts/pathology ; *Pancreatic Neoplasms/pathology ; *Duodenal Neoplasms/pathology ; *Common Bile Duct Neoplasms/surgery/pathology ; Retrospective Studies ; }, abstract = {BACKGROUND AND AIMS: Ampullary lesions (ALs) of the minor duodenal papilla are extremely rare. Endoscopic papillectomy (EP) is a routinely used treatment for AL of the major duodenal papilla, but the role of EP for minor AL has not been accurately studied.

METHODS: We identified 20 patients with ALs of minor duodenal papilla in the multicentric database from the Endoscopic Papillectomy vs Surgical Ampullectomy vs Pancreatitcoduodenectomy for Ampullary Neoplasm study, which included 1422 EPs. We used propensity score matching (nearest-neighbor method) to match these cases with ALs of the major duodenal papilla based on age, sex, histologic subtype, and size of the lesion in a 1:2 ratio. Cohorts were compared by means of chi-square or Fisher exact test as well as Mann-Whitney U test.

RESULTS: Propensity score-based matching identified a cohort of 60 (minor papilla 20, major papilla 40) patients with similar baseline characteristics. The most common histologic subtype of lesions of minor papilla was an ampullary adenoma in 12 patients (3 low-grade dysplasia and 9 high-grade dysplasia). Five patients revealed nonneoplastic lesions. Invasive cancer (T1a), adenomyoma, and neuroendocrine neoplasia were each found in 1 case. The rate of complete resection, en-bloc resection, and recurrences were similar between the groups. There were no severe adverse events after EP of lesions of minor papilla. One patient had delayed bleeding that could be treated by endoscopic hemostasis, and 2 patients showed a recurrence in surveillance endoscopy after a median follow-up of 21 months (interquartile range, 12-50 months).

CONCLUSIONS: EP is safe and effective in ALs of the minor duodenal papilla. Such lesions could be managed according to guidelines for EP of major duodenal papilla.}, } @article {pmid37950760, year = {2024}, author = {Beloribi-Djefaflia, S and Morales, RJ and Fatehi, F and Isapof, A and Servais, L and Leonard-Louis, S and Michaud, M and Verdure, P and Gidaro, T and Pouget, J and Poinsignon, V and Bonello-Palot, N and Attarian, S}, title = {Clinical and genetic features of patients suffering from CMT4J.}, journal = {Journal of neurology}, volume = {271}, number = {3}, pages = {1355-1365}, pmid = {37950760}, issn = {1432-1459}, mesh = {Adolescent ; Humans ; *Amyotrophic Lateral Sclerosis ; *Charcot-Marie-Tooth Disease/diagnosis/genetics ; *Flavoproteins/genetics ; Heterozygote ; Mutation/genetics ; Phenotype ; *Phosphoric Monoester Hydrolases/genetics ; }, abstract = {Mutations in the FIG4 gene have been identified in various diseases, including amyotrophic lateral sclerosis, Parkinson's disease, and Charcot-Marie-Tooth 4 J (CMT4J), with a wide range of phenotypic manifestations. We present eight cases of CMT4J patients carrying the p.Ile41Thr mutation of FIG4. The patients were categorized according to their phenotype. Six patients had a pure CMT; whereas, two patients had a CMT associated with parkinsonism. Three patients had an early onset and exhibited more severe forms of the disease. Three others experienced symptoms in their teenage years and had milder forms. Two patients had a late onset in adulthood. Four patients showed electrophysiological evidence of conduction blocks, typically associated with acquired neuropathies. Consequently, two of them received intravenous immunoglobulin treatment without a significant objective response. Interestingly, two heterozygous patients with the same mutations exhibited contrasting phenotypes, one having a severe early-onset form and the other experiencing a slow disease progression starting at the age of 49. Notably, although 7 out of 8 patients in this study were compound heterozygous for the p.Ile41Thr mutation, only one individual was found to be homozygous for this genetic variant and exhibited an early-onset, severe form of the disease. Additionally, one patient who developed the disease in his youth was also diagnosed with hereditary neuropathy with pressure palsies. Our findings provide insights into the CMT4J subtype by reporting on eight heterogeneous patient cases and highlight the potential for misdiagnosis when conduction blocks or asymmetrical nerve conduction study results are observed in patients with FIG4 mutations.}, } @article {pmid37950613, year = {2024}, author = {Gray, D and Lesley, R and Mayberry, EJ and Williams, L and McHutchison, C and Newton, J and Pal, S and Chandran, S and MacPherson, SE and Abrahams, S and , }, title = {Development, reliability, validity, and acceptability of the remote administration of the Edinburgh Cognitive and Behavioural ALS Screen (ECAS).}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {25}, number = {1-2}, pages = {96-103}, doi = {10.1080/21678421.2023.2278512}, pmid = {37950613}, issn = {2167-9223}, mesh = {Humans ; *Cognition Disorders/diagnosis/etiology/psychology ; *Amyotrophic Lateral Sclerosis/diagnosis/psychology ; Reproducibility of Results ; Pandemics ; Neuropsychological Tests ; Cognition ; }, abstract = {BACKGROUND: ALS clinical care and research has changed dramatically since the COVID-19 pandemic, accelerating the need for cognitive assessments to be adapted for remote use.

OBJECTIVES: To develop the remote administration method of the Edinburgh Cognitive and Behavioural ALS Screen (ECAS), and determine its reliability and validity. Methods: The validation process consisted of: (1) Two versions of the ECAS (A and B) were administered, one in-person and one remotely via video call in a randomized order to 27 people without ALS; (2) The ECAS was administered remotely to 24 pwALS, with a second rater independently scoring performance; and (3) Acceptability was assessed by gathering feedback from 17 pwALS and 19 clinicians and researchers about their experience of using the ECAS remotely.

RESULTS: In the group without ALS, the remote and in-person ECAS total scores were found to be equivalent, and a Bland-Altman plot showed good agreement between the two administration methods. In pwALS, there was excellent agreement between two raters (ICC = 0.99). Positive feedback was gained from pwALS, researchers and clinicians with regards to ease of process, convenience, time, and the environment.

CONCLUSIONS: These findings provide evidence of the reliability and validity of the remote administration of the ECAS for pwALS, with clinicians, researchers and pwALS viewing it as a good alternative to face-to-face administration.}, } @article {pmid37949994, year = {2023}, author = {McMackin, R and Bede, P and Ingre, C and Malaspina, A and Hardiman, O}, title = {Biomarkers in amyotrophic lateral sclerosis: current status and future prospects.}, journal = {Nature reviews. Neurology}, volume = {19}, number = {12}, pages = {754-768}, pmid = {37949994}, issn = {1759-4766}, support = {MALASPINA/APR13/817-791/MNDA_/Motor Neurone Disease Association/United Kingdom ; TURNER/OCT15/972-797/MNDA_/Motor Neurone Disease Association/United Kingdom ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis ; Biomarkers ; Prognosis ; Disease Progression ; Drug Development ; }, abstract = {Disease heterogeneity in amyotrophic lateral sclerosis poses a substantial challenge in drug development. Categorization based on clinical features alone can help us predict the disease course and survival, but quantitative measures are also needed that can enhance the sensitivity of the clinical categorization. In this Review, we describe the emerging landscape of diagnostic, categorical and pharmacodynamic biomarkers in amyotrophic lateral sclerosis and their place in the rapidly evolving landscape of new therapeutics. Fluid-based markers from cerebrospinal fluid, blood and urine are emerging as useful diagnostic, pharmacodynamic and predictive biomarkers. Combinations of imaging measures have the potential to provide important diagnostic and prognostic information, and neurophysiological methods, including various electromyography-based measures and quantitative EEG-magnetoencephalography-evoked responses and corticomuscular coherence, are generating useful diagnostic, categorical and prognostic markers. Although none of these biomarker technologies has been fully incorporated into clinical practice or clinical trials as a primary outcome measure, strong evidence is accumulating to support their clinical utility.}, } @article {pmid37949878, year = {2023}, author = {Nagel, G and Kurz, D and Peter, RS and Rosenbohm, A and Koenig, W and Dupuis, L and Bäzner, H and Börtlein, A and Dempewolf, S and Schabet, M and Hecht, M and Kohler, A and Opherk, C and Naegele, A and Sommer, N and Lindner, A and Tumani, H and Ludolph, AC and Rothenbacher, D}, title = {Cystatin C based estimation of chronic kidney disease and amyotrophic lateral sclerosis in the ALS registry Swabia: associated risk and prognostic value.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {19594}, pmid = {37949878}, issn = {2045-2322}, mesh = {Male ; Humans ; Aged ; Female ; Prognosis ; *Amyotrophic Lateral Sclerosis ; Case-Control Studies ; Prospective Studies ; Cystatin C ; *Renal Insufficiency, Chronic/complications ; Glomerular Filtration Rate ; Registries ; Creatinine ; Biomarkers ; }, abstract = {Kidney function as part of metabolic changes could be associated with amyotrophic lateral-sclerosis (ALS). We investigated the associations between estimated chronic kidney disease (CKD), based on the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) cystatin C equation, and the risk at onset and prognostic value of CKD for ALS. Between October 2010 and June 2014, 362 ALS cases (59.4% men, mean age 65.7 years) and 681 controls (59.5% men, means age 66.3 years) were included in a population-based case-control study based on the ALS registry Swabia in Southern Germany. All ALS cases were followed-up (median 89.7 months), 317 died. Serum samples were measured for cystatin C to estimate the glomerular filtration rate (eGFR) according to the CKD-EPI equation. Information on covariates were assessed by an interview-based standardized questionnaire. Conditional logistic regression models were applied to calculate odds ratios (OR) for risk of ALS associated with eGFR/CKD stages. Time-to-death associated with renal parameters at baseline was assessed in ALS cases only. ALS cases were characterized by lower body mass index, slightly lower smoking prevalence, more intense occupational work and lower education than controls. Median serum cystatin-C based eGFR concentrations were lower in ALS cases than in controls (54.0 vs. 59.5 mL/min pro 1.73 m[2]). The prevalence of CKD stage ≥ 3 was slightly higher in ALS cases than in controls (14.1 vs. 11.0%). In the adjusted models, CKD stage 2 (OR 1.82, 95% CI 1.32, 2.52) and stage 3 (OR 2.34, 95% CI 1.38, 3.96) were associated with increased ALS risk. In this cohort of ALS cases, eGFR and CKD stage ≥ 3 (HR 0.94; 95% CI 0.64, 1.38) were not associated with prognosis. In this case-control study, higher CKD stages were associated with increased ALS risk, while in the prospective cohort of ALS cases, no indication of an association of CysC-based CKD on mortality was seen. In addition, our work strengthens the importance to evaluate renal function using a marker independent of muscle mass in ALS patients.}, } @article {pmid37949836, year = {2024}, author = {Yang, L and Jasiqi, Y and Zettor, A and Vadas, O and Chiaravalli, J and Agou, F and Lashuel, HA}, title = {Effective Inhibition of TDP-43 Aggregation by Native State Stabilization.}, journal = {Angewandte Chemie (International ed. in English)}, volume = {63}, number = {3}, pages = {e202314587}, doi = {10.1002/anie.202314587}, pmid = {37949836}, issn = {1521-3773}, support = {1398//École Polytechnique Fédérale de Lausanne/ ; }, mesh = {Humans ; *TDP-43 Proteinopathies/genetics/metabolism ; *Amyotrophic Lateral Sclerosis/metabolism ; *Neurodegenerative Diseases ; DNA-Binding Proteins/chemistry ; }, abstract = {Preventing the misfolding or aggregation of transactive response DNA binding protein with 43 kDa (TDP-43) is the most actively pursued disease-modifying strategy to treat amyotrophic lateral sclerosis and other neurodegenerative diseases. In this work, we provide proof of concept that native state stabilization of TDP-43 is a viable and effective strategy for treating TDP-43 proteinopathies. Firstly, we leveraged the Cryo-EM structures of TDP-43 fibrils to design C-terminal substitutions that disrupt TDP-43 aggregation. Secondly, we showed that these substitutions (S333D/S342D) stabilize monomeric TDP-43 without altering its physiological properties. Thirdly, we demonstrated that binding native oligonucleotide ligands stabilized monomeric TDP-43 and prevented its fibrillization and phase separation in the absence of direct binding to the aggregation-prone C-terminal domain. Fourthly, we showed that the monomeric TDP-43 variant could be induced to aggregate in a controlled manner, which enabled the design and implementation of a high-throughput screening assay to identify native state stabilizers of TDP-43. Altogether, our findings demonstrate that different structural domains in TDP-43 could be exploited and targeted to develop drugs that stabilize the native state of TDP-43 and provide a platform to discover novel drugs to treat TDP-43 proteinopathies.}, } @article {pmid37948743, year = {2024}, author = {Wang, SW and Igarashi-Yokoi, T and Mochida, S and Fujinami, K and Ohno-Matsui, K}, title = {PREVALENCE AND CLINICAL FEATURES OF RADIAL FUNDUS AUTOFLUORESCENCE IN HIGH MYOPIC WOMEN.}, journal = {Retina (Philadelphia, Pa.)}, volume = {44}, number = {3}, pages = {446-454}, doi = {10.1097/IAE.0000000000003981}, pmid = {37948743}, issn = {1539-2864}, mesh = {Humans ; Female ; Child ; Adolescent ; Young Adult ; Adult ; Middle Aged ; Prevalence ; Fundus Oculi ; *Retinitis Pigmentosa/diagnosis ; *Myopia/diagnosis/epidemiology ; Electroretinography ; Retrospective Studies ; Fluorescein Angiography ; Tomography, Optical Coherence ; Eye Proteins ; }, abstract = {PURPOSE: To determine the prevalence and characteristics of radial fundus autofluorescence (FAF) in highly myopic women.

METHODS: This was a retrospective, observational case study to determine the prevalence of radial FAF in the ultra-widefield FAF images in women. The clinical characteristics of these patients were evaluated.

RESULTS: Fifteen of 1,935 (0.78%) highly myopic women were found to have radial FAF. Their mean age was 36.6 ± 25.6 years, and their mean best-corrected visual acuity was 0.3 ± 0.42 logMAR units. The mean axial length (AL) was 28.8 ± 2.8 mm. Among the 15 cases, eight did not have pigmentary changes and seven had pigmentary changes in the ultra-widefield FAF images. The women with the pigmentary changes were significantly older (P = 0.021), had poorer BCVA (P = 0.001), and had longer ALs (P = 0.002). The visual fields and electroretinograms were worse in the eyes with pigmentary changes.

CONCLUSION: The prevalence of radial FAF was 0.78% in women with high myopia. These patients might have mutations in the RPGR or RP2 genes and can develop high myopia and retinitis pigmentosa. Ultra-widefield FAF images should be examined in all highly myopic patients for early detection of radial FAF, and myopia prevention and genetic counseling for possible genetic therapy are recommended.}, } @article {pmid37948524, year = {2023}, author = {Ortega, JA and Sasselli, IR and Boccitto, M and Fleming, AC and Fortuna, TR and Li, Y and Sato, K and Clemons, TD and Mckenna, ED and Nguyen, TP and Anderson, EN and Asin, J and Ichida, JK and Pandey, UB and Wolin, SL and Stupp, SI and Kiskinis, E}, title = {CLIP-Seq analysis enables the design of protective ribosomal RNA bait oligonucleotides against C9ORF72 ALS/FTD poly-GR pathophysiology.}, journal = {Science advances}, volume = {9}, number = {45}, pages = {eadf7997}, pmid = {37948524}, issn = {2375-2548}, support = {R01 NS097850/NS/NINDS NIH HHS/United States ; R01 NS104219/NS/NINDS NIH HHS/United States ; R01 NS131409/NS/NINDS NIH HHS/United States ; R21 NS107761/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Humans ; *Frontotemporal Dementia/genetics ; *Amyotrophic Lateral Sclerosis/genetics ; C9orf72 Protein/genetics/metabolism ; RNA, Ribosomal/genetics ; Chromatin Immunoprecipitation Sequencing ; RNA/genetics ; Drosophila/genetics/metabolism ; DNA Repeat Expansion ; }, abstract = {Amyotrophic lateral sclerosis and frontotemporal dementia patients with a hexanucleotide repeat expansion in C9ORF72 (C9-HRE) accumulate poly-GR and poly-PR aggregates. The pathogenicity of these arginine-rich dipeptide repeats (R-DPRs) is thought to be driven by their propensity to bind low-complexity domains of multivalent proteins. However, the ability of R-DPRs to bind native RNA and the significance of this interaction remain unclear. Here, we used computational and experimental approaches to characterize the physicochemical properties of R-DPRs and their interaction with RNA. We find that poly-GR predominantly binds ribosomal RNA (rRNA) in cells and exhibits an interaction that is predicted to be energetically stronger than that for associated ribosomal proteins. Critically, modified rRNA "bait" oligonucleotides restore poly-GR-associated ribosomal deficits and ameliorate poly-GR toxicity in patient neurons and Drosophila models. Our work strengthens the hypothesis that ribosomal function is impaired by R-DPRs, highlights a role for direct rRNA binding in mediating ribosomal dysfunction, and presents a strategy for protecting against C9-HRE pathophysiological mechanisms.}, } @article {pmid37948306, year = {2023}, author = {Lai, Q and Mason, AH and Agarwal, A and Edenfield, WC and Zhang, X and Kobayashi, T and Kratish, Y and Marks, TJ}, title = {Rapid Polyolefin Hydrogenolysis by a Single-Site Organo-Tantalum Catalyst on a Super-Acidic Support: Structure and Mechanism.}, journal = {Angewandte Chemie (International ed. in English)}, volume = {62}, number = {50}, pages = {e202312546}, doi = {10.1002/anie.202312546}, pmid = {37948306}, issn = {1521-3773}, support = {DE-FG02-03ER15457//Office of Science/ ; ECCS-2025633//National Science Foundation/ ; NNA04CC36G//Ames Research Center/ ; DE-SC0001329//U.S. Department of Energy/ ; DE-AC02-06CH11357//U.S. Department of Energy/ ; DE-AC02-07CH11358//U.S. Department of Energy/ ; DE-SC0014664//Oak Ridge Institute for Science and Education/ ; }, abstract = {The novel electrophilic organo-tantalum catalyst AlS/TaNpx (1) (Np=neopentyl) is prepared by chemisorption of the alkylidene Np3 Ta=CH[t] Bu onto highly Brønsted acidic sulfated alumina (AlS). The proposed catalyst structure is supported by EXAFS, XANES, ICP, DRIFTS, elemental analysis, and SSNMR measurements and is in good agreement with DFT analysis. Catalyst 1 is highly effective for the hydrogenolysis of diverse linear and branched hydrocarbons, ranging from C2 to polyolefins. To the best of our knowledge, 1 exhibits one of the highest polyolefin hydrogenolysis activities (9,800 (CH2 units) ⋅ mol(Ta)[-1] ⋅ h[-1] at 200 °C/17 atm H2) reported to date in the peer-reviewed literature. Unlike the AlS/ZrNp2 analog, the Ta catalyst is more thermally stable and offers multiple potential C-C bond activation pathways. For hydrogenolysis, AlS/TaNpx is effective for a wide variety of pre- and post-consumer polyolefin plastics and is not significantly deactivated by standard polyolefin additives at typical industrial concentrations.}, } @article {pmid37947306, year = {2024}, author = {Ackrivo, J}, title = {Response to: "Pulmonary care for ALS: There is more to the story": We agree more than we disagree.}, journal = {Muscle & nerve}, volume = {69}, number = {1}, pages = {117-118}, pmid = {37947306}, issn = {1097-4598}, support = {K23 HL151879/HL/NHLBI NIH HHS/United States ; HL-151879/HL/NHLBI NIH HHS/United States ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy ; *Respiratory Insufficiency ; *Noninvasive Ventilation ; }, } @article {pmid37946793, year = {2023}, author = {Rogers, ML and Schultz, DW and Karnaros, V and Shepheard, SR}, title = {Urinary biomarkers for amyotrophic lateral sclerosis: candidates, opportunities and considerations.}, journal = {Brain communications}, volume = {5}, number = {6}, pages = {fcad287}, pmid = {37946793}, issn = {2632-1297}, support = {U01 NS107027/NS/NINDS NIH HHS/United States ; }, abstract = {Amyotrophic lateral sclerosis is a relentless neurodegenerative disease that is mostly fatal within 3-5 years and is diagnosed on evidence of progressive upper and lower motor neuron degeneration. Around 15% of those with amyotrophic lateral sclerosis also have frontotemporal degeneration, and gene mutations account for ∼10%. Amyotrophic lateral sclerosis is a variable heterogeneous disease, and it is becoming increasingly clear that numerous different disease processes culminate in the final degeneration of motor neurons. There is a profound need to clearly articulate and measure pathological process that occurs. Such information is needed to tailor treatments to individuals with amyotrophic lateral sclerosis according to an individual's pathological fingerprint. For new candidate therapies, there is also a need for methods to select patients according to expected treatment outcomes and measure the success, or not, of treatments. Biomarkers are essential tools to fulfil these needs, and urine is a rich source for candidate biofluid biomarkers. This review will describe promising candidate urinary biomarkers of amyotrophic lateral sclerosis and other possible urinary candidates in future areas of investigation as well as the limitations of urinary biomarkers.}, } @article {pmid37946741, year = {2023}, author = {Ebrahimi, A and Kamyab, A and Hosseini, S and Ebrahimi, S and Ashkani-Esfahani, S}, title = {Involvement of Coenzyme Q10 in Various Neurodegenerative and Psychiatric Diseases.}, journal = {Biochemistry research international}, volume = {2023}, number = {}, pages = {5510874}, pmid = {37946741}, issn = {2090-2247}, abstract = {Coenzyme Q10 (CoQ10), commonly known as ubiquinone, is a vitamin-like component generated in mitochondrial inner membranes. This molecule is detected broadly in different parts of the human body in various quantities. This molecule can be absorbed by the digestive system from various nutritional sources as supplements. CoQ10 exists in three states: in a of reduced form (ubiquinol), in a semiquinone radical form, and in oxidized ubiquinone form in different organs of the body, playing a crucial role in electron transportation and contributing to energy metabolism and oxygen utilization, especially in the musculoskeletal and nervous systems. Since the early 1980s, research about CoQ10 has become the interest for two reasons. First, CoQ10 deficiency has been found to have a link with cardiovascular, neurologic, and cancer disorders. Second, this molecule has an antioxidant and free-radical scavenger nature. Since then, several investigations have indicated that the drug may benefit patients with cardiovascular, neuromuscular, and neurodegenerative illnesses. CoQ10 may protect the neurological system from degeneration and degradation due to its antioxidant and energy-regulating activity in mitochondria. This agent has shown its efficacy in preventing and treating neurological diseases such as migraine, Parkinson's disease, Alzheimer's disease, Huntington's disease, amyotrophic lateral sclerosis, and Friedreich's ataxia. This study reviews the literature to highlight this agent's potential therapeutic effects in the mentioned neurological disorders.}, } @article {pmid37946655, year = {2023}, author = {Lochbaum, R and Hoffmann, TK and Greve, J and Hahn, J}, title = {[Medikamente als Auslöser Bradykinin-vermittelter Angioödeme - mehr als ACE-Hemmer].}, journal = {Journal der Deutschen Dermatologischen Gesellschaft = Journal of the German Society of Dermatology : JDDG}, volume = {21}, number = {11}, pages = {1283-1290}, doi = {10.1111/ddg.15154_g}, pmid = {37946655}, issn = {1610-0387}, } @article {pmid37945695, year = {2023}, author = {Faria Assoni, A and Giove Mitsugi, T and Wardenaar, R and Oliveira Ferreira, R and Farias Jandrey, EH and Machado Novaes, G and Fonseca de Oliveira Granha, I and Bakker, P and Kaid, C and Zatz, M and Foijer, F and Keith Okamoto, O}, title = {Neurodegeneration-associated protein VAPB regulates proliferation in medulloblastoma.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {19481}, pmid = {37945695}, issn = {2045-2322}, mesh = {Child ; Humans ; *Medulloblastoma/genetics ; *Cerebellar Neoplasms/genetics ; Cell Proliferation/genetics ; Vesicular Transport Proteins ; }, abstract = {VAMP (Vesicle-associated membrane protein)-associated protein B and C (VAPB) has been widely studied in neurodegenerative diseases such as ALS, but little is known about its role in cancer. Medulloblastoma is a common brain malignancy in children and arises from undifferentiated cells during neuronal development. Therefore, medulloblastoma is an interesting model to investigate the possible relationship between VAPB and tumorigenesis. Here we demonstrate that high VAPB expression in medulloblastoma correlates with decreased overall patient survival. Consistent with this clinical correlation, we find that VAPB is required for normal proliferation rates of medulloblastoma cells in vitro and in vivo. Knockout of VAPB (VAPB[KO]) delayed cell cycle progression. Furthermore, transcript levels of WNT-related proteins were decreased in the VAPB[KO]. We conclude that VAPB is required for proliferation of medulloblastoma cells, thus revealing VAPB as a potential therapeutic target for medulloblastoma treatment.}, } @article {pmid37945618, year = {2023}, author = {Ramon-Gonen, R and Dori, A and Shelly, S}, title = {Towards a practical use of text mining approaches in electrodiagnostic data.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {19483}, pmid = {37945618}, issn = {2045-2322}, mesh = {Humans ; Male ; Female ; Retrospective Studies ; Data Mining/methods ; *Brachial Plexus Neuropathies ; *Myasthenia Gravis ; *Polyneuropathies ; }, abstract = {Healthcare professionals produce abounding textual data in their daily clinical practice. Text mining can yield valuable insights from unstructured data. Extracting insights from multiple information sources is a major challenge in computational medicine. In this study, our objective was to illustrate how combining text mining techniques with statistical methodologies can yield new insights and contribute to the development of neurological and neuromuscular-related health information. We demonstrate how to utilize and derive knowledge from medical text, identify patient groups with similar diagnostic attributes, and examine differences between groups using demographical data and past medical history (PMH). We conducted a retrospective study for all patients who underwent electrodiagnostic (EDX) evaluation in Israel's Sheba Medical Center between May 2016 and February 2022. The data extracted for each patient included demographic data, test results, and unstructured summary reports. We conducted several analyses, including topic modeling that targeted clinical impressions and topic analysis to reveal age- and sex-related differences. The use of suspected clinical condition text enriched the data and generated additional attributes used to find associations between patients' PMH and the emerging diagnosis topics. We identified 6096 abnormal EMG results, of which 58% (n = 3512) were males. Based on the latent Dirichlet allocation algorithm we identified 25 topics that represent different diagnoses. Sex-related differences emerged in 7 topics, 3 male-associated and 4 female-associated. Brachial plexopathy, myasthenia gravis, and NMJ Disorders showed statistically significant age and sex differences. We extracted keywords related to past medical history (n = 37) and tested them for association with the different topics. Several topics revealed a close association with past medical history, for example, length-dependent symmetric axonal polyneuropathy with diabetes mellitus (DM), length-dependent sensory polyneuropathy with chemotherapy treatments and DM, brachial plexopathy with motor vehicle accidents, myasthenia gravis and NMJ disorders with botulin treatments, and amyotrophic lateral sclerosis with swallowing difficulty. Summarizing visualizations were created to easily grasp the results and facilitate focusing on the main insights. In this study, we demonstrate the efficacy of utilizing advanced computational methods in a corpus of textual data to accelerate clinical research. Additionally, using these methods allows for generating clinical insights, which may aid in the development of a decision-making process in real-life clinical practice.}, } @article {pmid37944939, year = {2024}, author = {Kalantari, F and Rendl, G and Hecht, S and Pirich, C and Beheshti, M}, title = {[Atypisches lokales Larynxkarzinom-Rezidiv imitiert als entzündlicher thyreoidaler Uptake in der 18F-FDG PET/CT].}, journal = {RoFo : Fortschritte auf dem Gebiete der Rontgenstrahlen und der Nuklearmedizin}, volume = {196}, number = {2}, pages = {195-196}, doi = {10.1055/a-2123-3867}, pmid = {37944939}, issn = {1438-9010}, mesh = {*Fluorodeoxyglucose F18 ; *Positron Emission Tomography Computed Tomography ; Positron-Emission Tomography ; Tomography, X-Ray Computed ; Radiopharmaceuticals ; }, } @article {pmid37944521, year = {2024}, author = {Yang, K and Tang, Z and Xing, C and Yan, N}, title = {STING signaling in the brain: Molecular threats, signaling activities, and therapeutic challenges.}, journal = {Neuron}, volume = {112}, number = {4}, pages = {539-557}, pmid = {37944521}, issn = {1097-4199}, support = {R01 AI151708/AI/NIAID NIH HHS/United States ; R01 NS117424/NS/NINDS NIH HHS/United States ; R01 NS122825/NS/NINDS NIH HHS/United States ; R56 AI151708/AI/NIAID NIH HHS/United States ; }, mesh = {Humans ; *Brain/pathology ; *Nervous System Diseases ; Signal Transduction ; }, abstract = {Stimulator of interferon genes (STING) is an innate immune signaling protein critical to infections, autoimmunity, and cancer. STING signaling is also emerging as an exciting and integral part of many neurological diseases. Here, we discuss recent advances in STING signaling in the brain. We summarize how molecular threats activate STING signaling in the diseased brain and how STING signaling activities in glial and neuronal cells cause neuropathology. We also review human studies of STING neurobiology and consider therapeutic challenges in targeting STING to treat neurological diseases.}, } @article {pmid37944503, year = {2023}, author = {Sun, HJ and Zhang, J and Lu, JP and Wu, MT}, title = {The Improvement in Function of Poststroke Spasticity by Vibrational and Heated Stone-Needle Therapy and Meridian Dredging Exercise: A Randomized, Controlled, Preliminary Trial.}, journal = {Complementary medicine research}, volume = {30}, number = {6}, pages = {492-501}, doi = {10.1159/000534993}, pmid = {37944503}, issn = {2504-2106}, mesh = {Humans ; Animals ; Mice ; *Quality of Life ; *Meridians ; Physical Therapy Modalities ; }, abstract = {BACKGROUND: Poststroke spasticity (PSS) is a common complication of stroke. Current PSS treatments have been linked to high costs, lack of long-term effectiveness, and undesirable side effects. Vibrational and heated stone-needle therapy (VHS) has not been utilized to treat PSS, and its safety and effectiveness have yet to be proven by high-quality clinical research.

OBJECTIVE: The aim of this study was to determine the effectiveness of VHS combined with meridian dredging exercise (MDE) in patients with PSS.

METHODS: One hundred participants with stroke were included and randomly assigned to a treatment group (VHS plus MDEs) and a control group (MDEs alone). Patients in both groups were treated for 4 weeks. The primary outcome measures were the Modified Ashworth Scale (MAS) and Fugl-Meyer Assessment (FMA), while the secondary outcome measures were the Activity of Daily Living (ADL) Scale and Stroke-Specific Quality of Life Scale (SS-QOL). The evaluations were at baseline (T0) at 4 weeks of treatment (T1) and at 12 weeks of follow-up without treatment (T2).

RESULTS: At T1 and T2, there were significant differences in MAS between the two groups (p = 0.001). From the perspective of distribution, the VHS plus MDE group had significant changes, and the group-time interactions of upper and lower extremities in FMA, ADL, and SS-QOL were statistically significant (p < 0.001), indicating that patients' symptoms improved after treatment. But the overall effect size is small, especially the effect size of improvement in SS-QOL at T1.

CONCLUSION: VHS in combination with MDE can consistently alleviate PSS, enhance limb function, and improve the quality of life of patients with PSS. But we need to optimize the device further and observe the improvement of patients for a more extended period.

UNLABELLED: HintergrundSpastik nach Schlaganfall (PSS; post-stroke spasticity) ist eine häufige Komplikation des Schlaganfalls. Gegenwärtige PSS-Behandlungen sind mit hohen Kosten, mangelnder langfristiger Wirksamkeit und unerwünschten Nebenwirkungen in Verbindung gebracht worden. Vibrierende und erhitzte Steinnadeln (VHS) sind bisher nicht zur Behandlung des PSS eingesetzt worden, und der Nachweis ihrer Sicherheit und Wirksamkeit durch hochwertige klinische Forschung steht noch aus.ZielBeurteilung der Wirksamkeit von vibrierenden und erhitzten Steinnadeln (VHS) in Kombination mit Meridian-Ausbagger-Übungen (MDE) bei Patienten mit PSS.Methoden100 Patienten mit Schlaganfall wurden eingeschlossen und per Randomisierung auf eine Behandlungsgruppe (VHS plus MDEs) und eine Kontrollgruppe (nur MDE) aufgeteilt. In beiden Gruppen wurden die Patienten 4 Wochen lang behandelt. Die primären Messinstrumente waren die Modified Ashworth Scale (MAS) und das Fugl-Meyer Assessment (FMA), als sekundäre Messinstrumente wurden die Activity of Daily Living Scale (ADL) und die Stroke-Specific Quality of Life Scale (SS-QOL) erhoben. Die Beurteilungszeitpunkte waren bei Baseline (T0) nach 4 Wochen Behandlung (T1) und nach 12 Wochen Nachbeobachtung ohne Behandlung (T2).ErgebnisseBei T1 und T2 bestanden signifikante Unterschiede bei der MAS zwischen den Gruppen (p = 0.001). Aus der Perspektive der Distribution zeigte die “VHS plus MDE”-Gruppe signifikante Veränderungen, und die Gruppe*Zeit-Interaktionen der oberen and unteren Extremitäten bei FMA, ADL und SS-QOL waren statistisch signifikant (p < 0.001), was darauf hindeutet, dass die Beschwerden der Patienten sich nach der Behandlung besserten. Die Effektstärke ist allerdings gering, insbesondere die der SS-QOL-Verbesserung bei T1.SchlussfolgerungDie Anwendung von vibrierenden und erhitzten Steinnadeln in Kombination mit Meridian-Ausbagger-Übungen kann PSS durchgängig lindern, die Funktion der Extremitäten verbessern und die Lebensqualität der Patienten mit PSS erhöhen. Jedoch muss das Produkt weiter optimiert werden, und die Verbesserungen bei den Patienten müssen über einen längeren Zeitraum beobachtet werden.}, } @article {pmid37942848, year = {2024}, author = {Soreq, H}, title = {Novel single-nucleus transcriptomics unravels developmental and functionally controlled principles of mammalian neuromuscular junctions.}, journal = {Journal of neurochemistry}, volume = {168}, number = {4}, pages = {339-341}, doi = {10.1111/jnc.15986}, pmid = {37942848}, issn = {1471-4159}, mesh = {Animals ; Humans ; Neuromuscular Junction/metabolism ; *Receptors, Nicotinic/genetics/metabolism ; Synaptic Transmission ; *Amyotrophic Lateral Sclerosis/metabolism ; Gene Expression Profiling ; Mammals/metabolism ; }, abstract = {Prof Ohno's team (Ohkawara et al. 2023, current issue) underscored the dynamic and functional features that co-shape the embryonic and early post-natal development of mammalian neuromuscular junctions (NMJs) using single-nucleus transcriptomics which provides specific insights into the activities of individually studied nuclei and their functional characteristics. Unlike other single-nucleus transcriptomics studies, which tend to be limited to single developmental time points, this article provides novel views of the complex developmental and regulatory dynamics and embryonic cell type origins underscoring the formation of functioning mammalian NMJs by combining this transcriptomic approach with interference tests in cultured C2C12 myotubes. This reveals intriguing novel links between the particular nicotinic acetylcholine receptor genes (nAChR) and regulator transcripts thereof and enables outlining the sequential development of functioning NMJs along embryogenesis and soon after delivery. Specifically, the timewise and cell type origins of the studied nuclei emerged as essential for NMJ neurogenesis and inter-cellular transfer of specific regulators has been indicated. Breaking the barriers between distinct research subdisciplines, this study opens new neurochemistry research directions that recombine developmental, regulatory, and functional transcriptomics in NMJ-including tissues. Moreover, these findings may facilitate tests of diverse pharmaceutical and therapeutic modulators of neuromuscular functioning in health and disease, assisting the translational research progress in treating devastating neuromuscular states such as in amyotrophic lateral sclerosis, myasthenia gravis or individuals poisoned occupationally or otherwise with anticholinesterase inhibitors.}, } @article {pmid37942236, year = {2023}, author = {Itou, J and Munakata, Y and Kuramitsu, Y and Madarame, H and Okazaki, K}, title = {Incidence and Distribution of Deep Vein Thrombosis Following Total Hip Arthroplasty Using an Anterolateral Supine Approach.}, journal = {Orthopedic research and reviews}, volume = {15}, number = {}, pages = {199-205}, pmid = {37942236}, issn = {1179-1462}, abstract = {PURPOSE: Venous thromboembolism (VTE) is a potential major complication in patients undergoing total hip arthroplasty (THA). However, the incidence of VTE following THA using anterolateral supine approach (ALS) has not been reported. The purpose of this study was to investigate the incidence of perioperative VTE and the distribution and characteristics of deep vein thrombosis (DVT) following ALS THA.

PATIENTS AND METHODS: This retrospective single-arm study analyzed the 182 consecutive hips of 164 patients who underwent primary ALS THA. Pharmacological prophylaxis consisted of enoxaparin 20 mg twice daily for approximately 6 days starting 24 h postoperatively until duplex ultrasonography was performed to determine whether postoperative DVT was present. DVT was assessed by whole-leg Doppler ultrasound, and the location and characteristics of any thrombus were recorded. If pulmonary thromboembolism was suspected, contrast-enhanced computed tomography was performed.

RESULTS: The overall incidence of VTE was 9.9% for DVT (18/182 hips) and 0.5% for pulmonary thromboembolism (1/182 hips). Most DVTs were in the soleal vein on the affected side and showed isoechoic or hypoechoic echogenicity. All thrombi were non-floating.

CONCLUSION: Following ALS THA with standard pharmacological prophylaxis and an early weight-bearing protocol, the incidence of perioperative DVT was approximately 10%, mostly occurring in the lower leg.}, } @article {pmid37942135, year = {2023}, author = {Shi, Y and Zhu, R}, title = {Analysis of damage-associated molecular patterns in amyotrophic lateral sclerosis based on ScRNA-seq and bulk RNA-seq data.}, journal = {Frontiers in neuroscience}, volume = {17}, number = {}, pages = {1259742}, pmid = {37942135}, issn = {1662-4548}, abstract = {BACKGROUND: Amyotrophic Lateral Sclerosis (ALS) is a devastating neurodegenerative disorder characterized by the progressive loss of motor neurons. Despite extensive research, the exact etiology of ALS remains elusive. Emerging evidence highlights the critical role of the immune system in ALS pathogenesis and progression. Damage-Associated Molecular Patterns (DAMPs) are endogenous molecules released by stressed or damaged cells, acting as danger signals and activating immune responses. However, their specific involvement in ALS remains unclear.

METHODS: We obtained single-cell RNA sequencing (scRNA-seq) data of ALS from the primary motor cortex in the Gene Expression Omnibus (GEO) database. To better understand genes associated with DAMPs, we performed analyses on cell-cell communication and trajectory. The abundance of immune-infiltrating cells was assessed using the single-sample Gene Set Enrichment Analysis (ssGSEA) method. We performed univariate Cox analysis to construct the risk model and utilized the least absolute shrinkage and selection operator (LASSO) analysis. Finally, we identified potential small molecule drugs targeting ALS by screening the Connectivity Map database (CMap) and confirmed their potential through molecular docking analysis.

RESULTS: Our study annotated 10 cell types, with the expression of genes related to DAMPs predominantly observed in microglia. Analysis of intercellular communication revealed 12 ligand-receptor pairs in the pathways associated with DAMPs, where microglial cells acted as ligands. Among these pairs, the SPP1-CD44 pair demonstrated the greatest contribution. Furthermore, trajectory analysis demonstrated distinct differentiation fates of different microglial states. Additionally, we constructed a risk model incorporating four genes (TRPM2, ROCK1, HSP90AA1, and HSPA4). The validity of the risk model was supported by multivariate analysis. Moreover, external validation from dataset GSE112681 confirmed the predictive power of the model, which yielded consistent results with datasets GSE112676 and GSE112680. Lastly, the molecular docking analysis suggested that five compounds, namely mead-acid, nifedipine, nifekalant, androstenol, and hydrastine, hold promise as potential candidates for the treatment of ALS.

CONCLUSION: Taken together, our study demonstrated that DAMP entities were predominantly observed in microglial cells within the context of ALS. The utilization of a prognostic risk model can accurately predict ALS patient survival. Additionally, genes related to DAMPs may present viable drug targets for ALS therapy.}, } @article {pmid37942130, year = {2023}, author = {Piñeros-Fernández, MC}, title = {Artificial Intelligence Applications in the Diagnosis of Neuromuscular Diseases: A Narrative Review.}, journal = {Cureus}, volume = {15}, number = {11}, pages = {e48458}, pmid = {37942130}, issn = {2168-8184}, abstract = {The accurate diagnosis of neuromuscular diseases (NMD) is in many cases difficult; the starting point is the clinical approach based on the course of the disease and a careful physical examination of the patient. Electrodiagnostic tests, imaging, muscle biopsy, and genetics are fundamental complementary studies for the diagnosis of NMD. The large volume of data obtained from such studies makes it necessary to look for efficient solutions, such as artificial intelligence (AI) applications, which can help classify, synthesize, and organize the information of patients with NMD to facilitate their accurate and timely diagnosis. The objective of this study was to describe the usefulness of AI applications in the diagnosis of patients with neuromuscular diseases. A narrative review was done, including publications on artificial intelligence applied to the diagnostic methods of NMD currently existing. Twelve studies were included. Two of the studies focused on muscle ultrasound, five of the studies on muscle MRI, two studies on electromyography, two studies on amyotrophic lateral sclerosis (ALS) biomarkers, and one study on genes related to myopathies. The accuracy of classification using different classification algorithms used in each of the studies included in this narrative review was already 90% in most studies. In conclusion, the future design of more accurate algorithms applied to NMD with greater precision will have an impact on the earlier diagnosis of this group of diseases.}, } @article {pmid37941924, year = {2023}, author = {Zaita, BM and Ghosh, A and Lee, S and Raymond, A and Agnihotri, T and Akhter, NM}, title = {Radiologically inserted gastrostomy tube in neurological disease: A retrospective study.}, journal = {Journal of clinical imaging science}, volume = {13}, number = {}, pages = {35}, pmid = {37941924}, issn = {2156-7514}, abstract = {OBJECTIVES: This study aimed to compare the safety and efficacy of balloon and non-balloon (or dilator) gastrostomy devices in radiologically inserted gastrostomy (RIG) for patients with neurological disease.

MATERIAL AND METHODS: A retrospective analysis of 152 patients was conducted at a tertiary care hospital from July 2017 to September 2020. 104 and 48 patients were included in the balloon and non-balloon groups, respectively. The frequency of complications per specific neurological indication as well as the breakdown of the different complications pertaining to each indication was recorded for analysis. The recovery time, fluoroscopy time, contrast volume, peak radiation, and pain management dosages for each procedure were all reviewed to evaluate for statistical differences between the balloon and non-balloon groups. An adjusted model odds ratio (OR) was conducted to evaluate how each of the variables (type of gastrostomy tube, body mass index [BMI], age, and gender) affected the frequency of complications within our cohort.

RESULTS: This study included 152 patients, with an average age of 65.17 years (interquartile range [IQR] = 12.66) and an average BMI of 26.97 (IQR = 7.19). The majority of patients were male (71.1%). The most common indication for the procedure was stroke (24.3%), followed by post-intubation dysphagia (16.4%) and intracranial hemorrhage (11.8%). Amyotrophic lateral sclerosis (ALS) and altered mental status had a similar prevalence at 9.9%. The overall complication rate was 33.8%, overall mortality rate 3.3%, 30-day mortality rate of 2.6%, and no other major complications according to CIRSE criteria. Notably, patients with neurodegenerative disorders exhibited comparable rates of minor complications: 33.3% in ALS (5/15 patients), 50% in myasthenia gravis (1/2 patients), and 100% in muscular dystrophy (1/1 patient). The study compared two groups: the balloon group (104 patients) and the dilator group (48 patients). The balloon group received significantly lower preoperative sedation in the form of fentanyl (Avg = 4.46 min vs. 6.54 min, P = 0.287). The balloon group had shorter fluoroscopy time, lower radiation exposure dose, and shorter operating time compared to the dilator group, though not statistically significant. In the logistic regression model, there was no statistical difference in complication rates between the dilator and balloon groups. BMI, age, and gender did not significantly affect minor complication rates.

CONCLUSION: RIG tube insertions may serve as a valuable, alternative approach in providing enteral support in patients with neurological disease.}, } @article {pmid37941604, year = {2023}, author = {Dyer, MS and Odierna, GL and Clark, RM and Woodhouse, A and Blizzard, CA}, title = {Synaptic remodeling follows upper motor neuron hyperexcitability in a rodent model of TDP-43.}, journal = {Frontiers in cellular neuroscience}, volume = {17}, number = {}, pages = {1274979}, pmid = {37941604}, issn = {1662-5102}, abstract = {Amyotrophic Lateral Sclerosis (ALS) is an incurable disease characterized by relentlessly progressive degeneration of the corticomotor system. Cortical hyperexcitability has been identified as an early pre-symptomatic biomarker of ALS. This suggests that hyperexcitability occurs upstream in the ALS pathological cascade and may even be part of the mechanism that drives development of symptoms or loss of motor neurons in the spinal cord. However, many studies also indicate a loss to the synaptic machinery that mediates synaptic input which raises the question of which is the driver of disease, and which is a homeostatic response. Herein, we used an inducible mouse model of TDP-43 mediated ALS that permits for the construction of detailed phenotypic timelines. Our work comprehensively describes the relationship between intrinsic hyperexcitability and altered synaptic input onto motor cortical layer 5 pyramidal neurons over time. As a result, we have constructed the most complete timeline of electrophysiological changes following induction of TDP-43 dysfunction in the motor cortex. We report that intrinsic hyperexcitability of layer 5 pyramidal neurons precedes changes to excitatory synaptic connections, which manifest as an overall loss of inputs onto layer 5 pyramidal neurons. This finding highlights the importance of hyperexcitability as a primary mechanism of ALS and re-contextualizes synaptic changes as possibly representing secondary adaptive responses. Recognition of the relationship between intrinsic hyperexcitability and reduced excitatory synaptic input has important implications for the development of useful therapies against ALS. Novel strategies will need to be developed that target neuronal output by managing excitability against synapses separately.}, } @article {pmid37941227, year = {2023}, author = {Young, H and Gerez, L and Cole, T and Inirio, B and Proietti, T and Closs, B and Paganoni, S and Walsh, C}, title = {Air Efficient Soft Wearable Robot for High-Torque Elbow Flexion Assistance.}, journal = {IEEE ... International Conference on Rehabilitation Robotics : [proceedings]}, volume = {2023}, number = {}, pages = {1-6}, doi = {10.1109/ICORR58425.2023.10304679}, pmid = {37941227}, issn = {1945-7901}, mesh = {Humans ; Elbow/physiology ; *Robotics ; *Elbow Joint ; Torque ; *Amyotrophic Lateral Sclerosis ; *Wearable Electronic Devices ; }, abstract = {Recent developments in soft wearable robots have shown promise for assistive and rehabilitative use-cases. For inflatable approaches, a major challenge in developing portable systems is finding a balance between portability, performance, and usability. In this paper, we present a textile-based robotic sleeve that can provide functional elbow flexion assistance and is compatible with a portable actuation unit (PAU). Flexion is driven by a curved textile actuator with internal pneumatic supports (IPS). We show that the addition of IPS improves torque generation and increases battery-powered actuations by 60%. We demonstrate that the device can provide enough torque throughout the ROM of the elbow joint for daily life assistance. Specifically, the device generates 13.5 Nm of torque at 90°. Experimental testing in five healthy individuals and two individuals with Amyotrophic Lateral Sclerosis (ALS) demonstrates its impact on wearer muscle activity and kinematics. The results with healthy subjects show that the device was able to reduce the bicep muscle activity by an average of 49.1±13.3% during static and dynamic exercises, 43.6±11.1% during simulated ADLs, and provided an assisted ROM of 134°±13°. Both ALS participants reported a reduced rate of perceived exertion during both static and dynamic tasks while wearing the device and had an average ROM of 115°±8°. Future work will explore other applications of the IPS and extend the approach to assisting multiple joints.}, } @article {pmid37941028, year = {2023}, author = {Huang, Y and Liu, B and Sinha, SC and Amin, S and Gan, L}, title = {Mechanism and therapeutic potential of targeting cGAS-STING signaling in neurological disorders.}, journal = {Molecular neurodegeneration}, volume = {18}, number = {1}, pages = {79}, pmid = {37941028}, issn = {1750-1326}, support = {R01 AG074541/AG/NIA NIH HHS/United States ; R01AG072758/AG/NIA NIH HHS/United States ; R01AG074541/AG/NIA NIH HHS/United States ; R01AG054214/AG/NIA NIH HHS/United States ; }, mesh = {Humans ; Signal Transduction/physiology ; Nucleotidyltransferases/genetics/metabolism ; DNA/metabolism ; *Interferon Type I/genetics/metabolism ; *Nervous System Diseases ; }, abstract = {DNA sensing is a pivotal component of the innate immune system that is responsible for detecting mislocalized DNA and triggering downstream inflammatory pathways. Among the DNA sensors, cyclic GMP-AMP synthase (cGAS) is a primary player in detecting cytosolic DNA, including foreign DNA from pathogens and self-DNA released during cellular damage, culminating in a type I interferon (IFN-I) response through stimulator of interferon genes (STING) activation. IFN-I cytokines are essential in mediating neuroinflammation, which is widely observed in CNS injury, neurodegeneration, and aging, suggesting an upstream role for the cGAS DNA sensing pathway. In this review, we summarize the latest developments on the cGAS-STING DNA-driven immune response in various neurological diseases and conditions. Our review covers the current understanding of the molecular mechanisms of cGAS activation and highlights cGAS-STING signaling in various cell types of central and peripheral nervous systems, such as resident brain immune cells, neurons, and glial cells. We then discuss the role of cGAS-STING signaling in different neurodegenerative conditions, including tauopathies, Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis, as well as aging and senescence. Finally, we lay out the current advancements in research and development of cGAS inhibitors and assess the prospects of targeting cGAS and STING as therapeutic strategies for a wide spectrum of neurological diseases.}, } @article {pmid37939393, year = {2023}, author = {Lualdi, M and Casale, F and Rizzone, MG and Zibetti, M and Monti, C and Colugnat, I and Calvo, A and De Marco, G and Moglia, C and Fuda, G and Comi, C and Chiò, A and Lopiano, L and Fasano, M and Alberio, T}, title = {Shared and Unique Disease Pathways in Amyotrophic Lateral Sclerosis and Parkinson's Disease Unveiled in Peripheral Blood Mononuclear Cells.}, journal = {ACS chemical neuroscience}, volume = {14}, number = {23}, pages = {4240-4251}, pmid = {37939393}, issn = {1948-7193}, mesh = {Humans ; *Parkinson Disease/metabolism ; *Amyotrophic Lateral Sclerosis/metabolism ; Prospective Studies ; Leukocytes, Mononuclear/metabolism ; Proteomics ; }, abstract = {Recent evidence supports an association between amyotrophic lateral sclerosis (ALS) and Parkinson's disease (PD). Indeed, prospective population-based studies demonstrated that about one-third of ALS patients develop parkinsonian (PK) signs, even though different neuronal circuitries are involved. In this context, proteomics represents a valuable tool to identify unique and shared pathological pathways. Here, we used two-dimensional electrophoresis to obtain the proteomic profile of peripheral blood mononuclear cells (PBMCs) from PD and ALS patients including a small cohort of ALS patients with parkinsonian signs (ALS-PK). After the removal of protein spots correlating with confounding factors, we applied a sparse partial least square discriminant analysis followed by recursive feature elimination to obtain two protein classifiers able to discriminate (i) PD and ALS patients (30 spots) and (ii) ALS-PK patients among all ALS subjects (20 spots). Functionally, the glycolysis pathway was significantly overrepresented in the first signature, while extracellular interactions and intracellular signaling were enriched in the second signature. These results represent molecular evidence at the periphery for the classification of ALS-PK as ALS patients that manifest parkinsonian signs, rather than comorbid patients suffering from both ALS and PD. Moreover, we confirmed that low levels of fibrinogen in PBMCs is a characteristic feature of PD, also when compared with another movement disorder. Collectively, we provide evidence that peripheral protein signatures are a tool to differentially investigate neurodegenerative diseases and highlight altered biochemical pathways.}, } @article {pmid37939160, year = {2023}, author = {Gendron, TF and Petrucelli, L}, title = {Immunological drivers of amyotrophic lateral sclerosis.}, journal = {Science translational medicine}, volume = {15}, number = {721}, pages = {eadj9332}, doi = {10.1126/scitranslmed.adj9332}, pmid = {37939160}, issn = {1946-6242}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/pathology ; Biomarkers ; }, abstract = {Amyotrophic lateral sclerosis (ALS), a devastating motor neuron disease involving complex genetic and environmental factors, is associated with neuroinflammation. Preclinical and clinical studies support immune system involvement in ALS pathogenesis, thereby spurring investigations into potential pathogenic mechanisms, immune response biomarkers, and ALS therapeutics.}, } @article {pmid37938192, year = {2023}, author = {Maharaj, D and Kaur, K and Saltese, A and Gouvea, J}, title = {Personalized Precision Immunotherapy for Amyotrophic Lateral Sclerosis (ALS).}, journal = {Critical reviews in immunology}, volume = {43}, number = {2}, pages = {1-11}, doi = {10.1615/CritRevImmunol.2023048372}, pmid = {37938192}, issn = {1040-8401}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/therapy ; Immunotherapy ; Brain ; Cytokines ; Inflammation ; }, abstract = {Neurological syndrome amyotrophic lateral sclerosis (ALS) affects motor neurons and is characterized by progressive motor neuron loss in the brain and spinal cord. ALS starts with mainly focal onset but when the disease progresses, it spreads to different parts of the body, with survival limits of 2-5 years after disease initiation. To date, only supportive care is provided for ALS patients, and no effective treatment or cure has been discovered. This review is focused on clinical and immunological aspects of ALS patients, based on our case studies, and we discuss the treatment we have provided to those patients based on a detailed evaluation of their peripheral blood immune cells and blood-derived serum secreted factors, cytokines, chemokines and growth factors. We show that using a personalized approach of low dose immunotherapy there is an improvement in the effects on inflammation and immunological dysfunction.}, } @article {pmid37935449, year = {2024}, author = {Darke, AC}, title = {Can I Be Honest With My Neurologist? A Problem of Health Technology Assessment in Canada.}, journal = {The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques}, volume = {51}, number = {5}, pages = {603-605}, doi = {10.1017/cjn.2023.307}, pmid = {37935449}, issn = {0317-1671}, } @article {pmid37934576, year = {2023}, author = {Gao, H and Yu, J and Chen, J and Wang, H and Liang, S and Feng, Z and Gu, Y and Dong, L}, title = {Target-Site and Metabolic Resistance Mechanisms to Penoxsulam in Late Watergrass (Echinochloa phyllopogon) in China.}, journal = {Journal of agricultural and food chemistry}, volume = {71}, number = {46}, pages = {17742-17751}, doi = {10.1021/acs.jafc.3c05921}, pmid = {37934576}, issn = {1520-5118}, mesh = {*Echinochloa/genetics/metabolism ; Herbicide Resistance/genetics ; Tandem Mass Spectrometry ; *Herbicides/pharmacology/metabolism ; *Acetolactate Synthase/genetics/metabolism ; }, abstract = {Echinochloa phyllopogon, a malignant weed in Northeast China's paddy fields, is currently presenting escalating resistance concerns. Our study centered on the HJHL-715 E. phyllopogon population, which showed heightened resistance to penoxsulam, through a whole-plant bioassay. Pretreatment with a P450 inhibitor malathion significantly increased penoxsulam sensitivity in resistant plants. In order to determine the resistance mechanism of the resistant population, we purified the resistant population from individual plants and isolated target-site resistance (TSR) and nontarget-site resistance (NTSR) materials. Pro-197-Thr and Trp-574-Leu mutations in acetolactate synthase (ALS) 1 and ALS2 of the resistant population drove reduced sensitivity of penoxsulam to the target-site ALS, the primary resistance mechanisms. To fully understand the NTSR mechanism, NTSR materials were investigated by using RNA-sequencing (RNA-seq) combined with a reference genome. High-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) analysis further supported the enhanced penoxsulam metabolism in NTSR materials. Gene expression data and quantitative reverse transcription polymerase chain reaction (qRT-PCR) validation confirmed 29 overexpressed genes under penoxsulam treatment, with 16 genes concurrently upregulated with quinclorac and metamifop treatment. Overall, our study confirmed coexisting TSR and NTSR mechanisms in E. phyllopogon's resistance to ALS inhibitors.}, } @article {pmid37934011, year = {2024}, author = {Palmieri, JL and Bach, JR}, title = {Pulmonary care for ALS: There is more to the story.}, journal = {Muscle & nerve}, volume = {69}, number = {1}, pages = {115-116}, doi = {10.1002/mus.27996}, pmid = {37934011}, issn = {1097-4598}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy ; }, } @article {pmid37933884, year = {2024}, author = {Walter, U and Sobiella, G and Prudlo, J and Batchakaschvili, M and Böhmert, J and Storch, A and Hermann, A}, title = {Ultrasonic detection of vagus, accessory, and phrenic nerve atrophy in amyotrophic lateral sclerosis: Relation to impairment and mortality.}, journal = {European journal of neurology}, volume = {31}, number = {2}, pages = {e16127}, pmid = {37933884}, issn = {1468-1331}, support = {GHS-15-0017//European Regional Development Fund/ ; //Hermann und Lilly Schilling-Stiftung für Medizinische Forschung/ ; }, mesh = {Adult ; Humans ; *Amyotrophic Lateral Sclerosis/complications/diagnostic imaging ; Atrophy ; Phrenic Nerve/diagnostic imaging ; Ultrasonics ; Vagus Nerve ; Male ; Female ; }, abstract = {BACKGROUND AND PURPOSE: In amyotrophic lateral sclerosis (ALS), phrenic nerve (PN) atrophy has been found, whereas there is controversy regarding vagus nerve (VN) atrophy. Here, we aimed to find out whether PN atrophy is related to respiratory function and 12-month survival. Moreover, we investigated the relevance of VN and spinal accessory nerve (AN) atrophy in ALS.

METHODS: This prospective observational monocentric study included 80 adult participants (40 ALS patients, 40 age- and sex-matched controls). The cross-sectional area (CSA) of bilateral cervical VN, AN, and PN was measured on high-resolution ultrasonography. Clinical assessments included the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R), the Non-Motor Symptoms Questionnaire, and handheld spirometry of forced vital capacity (FVC). One-year survival was documented.

RESULTS: The CSA of each nerve, VN, AN, and PN, was smaller in ALS patients compared to controls. VN atrophy was unrelated to nonmotor symptom scores. PN CSA correlated with the respiratory subscore of the ALSFRS-R (Spearman test, r = 0.59, p < 0.001), the supine FVC (r = 0.71, p < 0.001), and the relative change of sitting-supine FVC (r = -0.64, p = 0.001). Respiratory impairment was predicted by bilateral mean PN CSA (p = 0.046, optimum cutoff value of ≤0.37 mm[2] , sensitivity = 92%, specificity = 56%) and by the sum of PN and AN CSA (p = 0.036). The combination of ALSFRS-R score with PN and AN CSA measures predicted 1-year survival with similar accuracy as the combination of ALSFRS-R score and FVC.

CONCLUSIONS: Ultrasonography detects degeneration of cranial nerve motor fibers. PN and AN calibers are tightly related to respiratory function and 1-year survival in ALS.}, } @article {pmid37931706, year = {2024}, author = {Xuan, X and Zheng, G and Zhu, W and Sun, Q and Zeng, Y and Du, J and Huang, X}, title = {Alterations in regional homogeneity and functional connectivity in the cerebellum of patients with sporadic amyotrophic lateral sclerosis.}, journal = {Behavioural brain research}, volume = {458}, number = {}, pages = {114749}, doi = {10.1016/j.bbr.2023.114749}, pmid = {37931706}, issn = {1872-7549}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/pathology ; Magnetic Resonance Imaging/methods ; Brain ; Cerebellum/pathology ; }, abstract = {OBJECTIVE: The purpose of this study was to examine the cerebellum's local and global functional characteristics in individuals with sporadic amyotrophic lateral sclerosis (sALS) and their correlation with clinical data.

METHODS: Resting-state functional magnetic resonance imaging was performed on 39 patients with sALS and on 23 healthy controls. Regional homogeneity (ReHo) in the cerebellum of all participants was analyzed, and the cerebellar regions with differences in ReHo were considered regions of interest (ROIs). In addition, the functional connectivity between the ROIs and other brain regions was analyzed.

RESULTS: In patients with sALS, ReHo increased in parts of the posterior cerebellar lobe. Then, the two regions with increased ReHo of the cerebellum were used as seeds, and further analysis revealed that the connectivity of the right cerebellum to the right medial superior frontal gyrus, left lingual gyrus (calcarine sulcus), left precentral gyrus, left supplementary motor area, and right Crus II was significantly increased.

CONCLUSION: The results demonstrate that resting-state functional connectivity changes in both motor and extra-motor regions of the cerebellum in patients with sALS, and that the cerebellum plays a pathophysiological role in sALS.}, } @article {pmid38344317, year = {2022}, author = {Baziyar, P and Seyedalipour, B and Hosseinkhani, S and Nazifi, E}, title = {Development of In Silico Analysis and Molecular Dynamics Simulation on L67P and D76Y Mutants of the Human Superoxide Dismutase 1(hSOD1) Related to Amyotrophic Lateral Sclerosis.}, journal = {Iranian journal of biotechnology}, volume = {20}, number = {4}, pages = {e3178}, pmid = {38344317}, issn = {1728-3043}, abstract = {BACKGROUND: One neurodegenerative disorder that is caused by a mutation in the hSOD1 gene is Amyotrophic lateral sclerosis (ALS).

OBJECTIVES: The current study was developed in order to evaluate the effect exerted by two ALS-associated point mutations, L67P and D76Y are located in the metal-binding loop, on structural characterization of hSOD1 protein using molecular dynamics (MD) simulations and computational predictions.

MATERIALS AND METHODS: In this study, GROMACS was utilized to perform molecular dynamics simulations along with 9 different algorithms such as Predict SNP, PhD-SNP, MAPP, PolyPhen-1, Polyphen-2, SNP, SIFT, SNP&GO, and PMUT for predicting and also evaluating the mutational effect on the structural and conformational characterization of hSOD1.

RESULTS: Our study was done by several programs predicting the destabilizing and harmful effect exerted by mutant hSOD1. The deleterious effect of L67P mutation was predicted by MAPP and PhD-SNP algorithms, and D76Y mutation was predicted by 9 algorithms. Comparative studies that were conducted on mutants and wild-type indicated the altar in flexibility and protein conformational stability influenced the metal-binding loop's conformation. The outcomes of the MD exhibited an increase and decrease of flexibility for D76Y and L67P mutants compared to the wild type, respectively. On the other hand, analysis of the gyration radius indicated lower and higher compactness for D76Y and L67P, respectively, suggesting that replacing amino acid at the metal-binding loop can alter the protein compactness compared with the protein the wild type.

CONCLUSIONS: Overall, these findings provided insight into the effect of mutations on the hSOD1, which leads to neurodegeneration disorders in humans. The results show that the mutations of L67P and D76Y influence the stability of protein conformational and flexibility associated with ALS disease. Thus, results of such mutations are can be a prerequisite to achieve a thorough understanding of ALS pathogenicity.}, } @article {pmid38177466, year = {2022}, author = {Ramamoorthy, D and Severson, K and Ghosh, S and Sachs, K and , and Glass, JD and Fournier, CN and , and , and Herrington, TM and Berry, JD and Ng, K and Fraenkel, E}, title = {Identifying patterns in amyotrophic lateral sclerosis progression from sparse longitudinal data.}, journal = {Nature computational science}, volume = {2}, number = {9}, pages = {605-616}, pmid = {38177466}, issn = {2662-8457}, support = {IK2 CX001595/CX/CSRD VA/United States ; K23 NS099380/NS/NINDS NIH HHS/United States ; U54 NS091046/NS/NINDS NIH HHS/United States ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis ; Disease Progression ; *Neurodegenerative Diseases ; *Parkinson Disease/diagnosis ; }, abstract = {The clinical presentation of amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease, varies widely across patients, making it challenging to determine if potential therapeutics slow progression. We sought to determine whether there were common patterns of disease progression that could aid in the design and analysis of clinical trials. We developed an approach based on a mixture of Gaussian processes to identify clusters of patients sharing similar disease progression patterns, modeling their average trajectories and the variability in each cluster. We show that ALS progression is frequently nonlinear, with periods of stable disease preceded or followed by rapid decline. We also show that our approach can be extended to Alzheimer's and Parkinson's diseases. Our results advance the characterization of disease progression of ALS and provide a flexible modeling approach that can be applied to other progressive diseases.}, } @article {pmid38505242, year = {2022}, author = {Mendive-Tapia, L and Mendive-Tapia, D and Zhao, C and Gordon, D and Benson, S and Bromley, MJ and Wang, W and Wu, J and Kopp, A and Ackermann, L and Vendrell, M}, title = {Rationales Design von Phe-BODIPY-Aminosäuren als fluorogene Bausteine für den peptidbasierten Nachweis von Candida-Infektionen im Harntrakt.}, journal = {Angewandte Chemie (Weinheim an der Bergstrasse, Germany)}, volume = {134}, number = {17}, pages = {e202117218}, pmid = {38505242}, issn = {0044-8249}, } @article {pmid38011426, year = {2022}, author = {Fateh, HR and Askary-Kachoosangy, R and Shirzad, N and Akbarzadeh-Baghban, A and Fatehi, F}, title = {The effect of energy conservation strategies on fatigue, function, and quality of life in adults with motor neuron disease: Randomized controlled trial.}, journal = {Current journal of neurology}, volume = {21}, number = {2}, pages = {83-90}, pmid = {38011426}, issn = {2717-011X}, abstract = {Background: Fatigue is one of the most frequent complaints in patients with motor neuron diseases (MNDs), with a significant impact on the quality of life (QOL). There is lack of enough evidence for current pharmacological or non-pharmacological treatments of fatigue in this population to be applied in clinical setting. Energy conservation strategies are one of the key interventions for fatigue management in chronic diseases. We aimed to investigate the effect of applying these techniques in the fatigue management of patients with MND. Methods: This randomized controlled trial (RCT) study was carried out on 28 patients with MND. Participants were randomly assigned to either the intervention or control group. In addition to routine treatment, patients in the intervention group participated in 3 weekly 1-hour energy conservation programs provided by an experienced occupational therapist. The Fatigue Severity Scale (FSS) score, 36-Item Short Form Survey (SF-36), and Canadian Occupational Performance Measure (COPM) were measured at baseline, immediately after the last intervention session, and one month later. Results: FSS and COPM significantly changed after the course in the intervention group (P < 0.001 and P = 0.001, respectively). Both FSS and COPM improved significantly toward the final assessment only in the intervention group. The SF-36 changes were not significant in each of the groups. Conclusion: According to the findings of the present study, using energy conservation strategies could lead to better mid-term fatigue management and occupational performance improvement, but it did not improve QOL in patients with MND.}, } @article {pmid38283317, year = {2022}, author = {Cheung, K and Mitsumoto, H}, title = {Evaluating Personalized (N-of-1) Trials in Rare Diseases: How Much Experimentation Is Enough?.}, journal = {Harvard data science review}, volume = {2022}, number = {Spec Iss 3}, pages = {}, pmid = {38283317}, issn = {2644-2353}, support = {P30 AG063786/AG/NIA NIH HHS/United States ; R01 LM012836/LM/NLM NIH HHS/United States ; R01 MH109496/MH/NIMH NIH HHS/United States ; UL1 TR001873/TR/NCATS NIH HHS/United States ; }, abstract = {For rare diseases, conducting large, randomized trials of new treatments can be infeasible due to limited sample size, and it may answer the wrong scientific questions due to heterogeneity of treatment effects. Personalized (N-of-1) trials are multi-period crossover studies that aim to estimate individual treatment effects, thereby identifying the optimal treatments for individuals. This article examines the statistical design issues of evaluating a personalized (N-of-1) treatment program in people with amyotrophic lateral sclerosis (ALS). We propose an evaluation framework based on an analytical model for longitudinal data observed in a personalized trial. Under this framework, we address two design parameters: length of experimentation in each trial and number of trials needed. For the former, we consider patient-centric design criteria that aim to maximize the benefits of enrolled patients. Using theoretical investigation and numerical studies, we demonstrate that, from a patient's perspective, the duration of an experimentation period should be no longer than one-third of the entire follow-up period of the trial. For the latter, we provide analytical formulae to calculate the power for testing quality improvement due to personalized trials in a randomized evaluation program and hence determine the required number of trials needed for the program. We apply our theoretical results to design an evaluation program for ALS treatments informed by pilot data and show that the length of experimentation has a small impact on power relative to other factors such as the degree of heterogeneity of treatment effects.}, } @article {pmid37994346, year = {2022}, author = {Yang, C and Qian, C and Singh, N and Xiao, C and Westover, MB and Solomonik, E and Sun, J}, title = {ATD: Augmenting CP Tensor Decomposition by Self Supervision.}, journal = {Advances in neural information processing systems}, volume = {35}, number = {}, pages = {32039-32052}, pmid = {37994346}, issn = {1049-5258}, support = {R01 NS102190/NS/NINDS NIH HHS/United States ; RF1 NS120947/NS/NINDS NIH HHS/United States ; R01 HL161253/HL/NHLBI NIH HHS/United States ; R01 NS126282/NS/NINDS NIH HHS/United States ; R01 NS107291/NS/NINDS NIH HHS/United States ; }, abstract = {Tensor decompositions are powerful tools for dimensionality reduction and feature interpretation of multidimensional data such as signals. Existing tensor decomposition objectives (e.g., Frobenius norm) are designed for fitting raw data under statistical assumptions, which may not align with downstream classification tasks. In practice, raw input tensor can contain irrelevant information while data augmentation techniques may be used to smooth out class-irrelevant noise in samples. This paper addresses the above challenges by proposing augmented tensor decomposition (ATD), which effectively incorporates data augmentations and self-supervised learning (SSL) to boost downstream classification. To address the non-convexity of the new augmented objective, we develop an iterative method that enables the optimization to follow an alternating least squares (ALS) fashion. We evaluate our proposed ATD on multiple datasets. It can achieve 0.8% ~ 2.5% accuracy gain over tensor-based baselines. Also, our ATD model shows comparable or better performance (e.g., up to 15% in accuracy) over self-supervised and autoencoder baselines while using less than 5% of learnable parameters of these baseline models.}, } @article {pmid38505660, year = {2021}, author = {Romero, E and Jones, BS and Hogg, BN and Rué Casamajo, A and Hayes, MA and Flitsch, SL and Turner, NJ and Schnepel, C}, title = {Enzymkatalysierte späte Modifizierungen: Besser spät als nie.}, journal = {Angewandte Chemie (Weinheim an der Bergstrasse, Germany)}, volume = {133}, number = {31}, pages = {16962-16993}, pmid = {38505660}, issn = {0044-8249}, } @article {pmid38011420, year = {2021}, author = {Eishi-Oskouei, A and Basiri, K}, title = {Safety and efficacy of edaravone in well-defined Iranian patients with amyotrophic lateral sclerosis: A parallel-group single-blind trial.}, journal = {Current journal of neurology}, volume = {20}, number = {1}, pages = {1-7}, pmid = {38011420}, issn = {2717-011X}, abstract = {Background: This parallel-group single-blind trial evaluates the safety and efficacy of Edaravone, as a free radical scavenger, in a highly selective subgroup of Iranian patients with amyotrophic lateral sclerosis (ALS). Methods: The study was registered in ClinicalTrials.gov (registration number: NCT03272802) and Iranian Registry of Clinical Trials (registration number: IRCT20190324043105N). Patients were included into the study, who were diagnosed as probable or definite ALS (according to revised El Escorial criteria), mildly to moderately affected by the disease [according to Amyotrophic Lateral Sclerosis Health State Scale (ALS/HSS)], scored ≥ 2 points on all items of the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R), and had forced vital capacity (FVC) of at least 80%. 20 patients (10 cases, 10 controls) were observed for 12 cycles (each cycle lasted four weeks). Cases received Edaravone for the first 14 days in the first cycle and for the first 10 days in the next cycles. In addition, all patients received Riluzole. The 40-item Amyotrophic Lateral Sclerosis Assessment Questionnaire (ALSAQ-40), ALSFRS-R, and Manual Muscle Testing (MMT) scores were measured every 3 cycles to evaluate the physical and functional status of the patients. Besides, injection reactions, adverse events (AEs), and serious adverse events (SAEs) were measured during the study. Results: ALSAQ-40, ALSFRS-R, and MMT scores were not significantly different between cases and controls in 5 different time points. During the study, no injection reactions were observed. AEs and SAEs were not significantly different between cases and controls. Conclusion: Our data did not demonstrate efficacy of Edaravone in ALS treatment, but showed its safety for use in patients with ALS. Further studies are necessary to investigate Edaravone efficacy in patients with ALS before prescribing this new drug outside Japan.}, } @article {pmid38011400, year = {2021}, author = {Afrakhteh, M and Esmaeili, S and Shati, M and Shojaei, SF and Bahadori, M and Zamani, B and Almasi-Doghaee, M and Haghi-Ashtiani, B}, title = {Validating the Persian version of the amyotrophic lateral sclerosis-specific quality of life-revised instrument.}, journal = {Current journal of neurology}, volume = {20}, number = {1}, pages = {37-42}, pmid = {38011400}, issn = {2717-011X}, abstract = {Background: Amyotrophic Lateral Sclerosis-Specific Quality of Life-Revised (ALSSQOL-R) encompasses 50 items which assess quality of life (QOL) in patients with amyotrophic lateral sclerosis (ALS) in six major domains. This study aims to translate the ALSSQOL-R into Persian and evaluate its reliability and validity among Iranian patients. Methods: ALSSQOL-R was translated by the standard multi-step forward-backward method. Content validity was calculated using item content validity index (I-CVI). Three items in the "intimacy" domain were deleted considering Iranian culture. Cronbach's alpha was used for all 6 dimensions to calculate the internal consistency reliability. Test-retest reliability was evaluated using intraclass correlation coefficient (ICC) with one-month interval. Concurrent validity was measured by the validated version of 36-Item Short Form Health Survey (SF-36) questionnaire. Results: Sixty-three patients with ALS were enrolled in the study. I-CVI was 70%, promoted to 85% after modifications (acceptable). Regarding internal consistency reliability, Cronbach's alpha in all six domains was 0.70 and total Cronbach's alpha was 0.89 which is assumed as good. In terms of test-retest reliability, ICC [95% confidence interval (CI)] was 0.91 (91%) and Pearson correlation coefficient (r) was 0.90 (P < 0.001), all indicating an excellent reliability. The concurrent validity was established based on a strong correlation with SF-36 (r = 0.744, P < 0.001). Conclusion: The findings show that the modified Persian version of ALSSQOL-R is a valid and reliable QOL questionnaire which can be used for Iranian patients with ALS in both clinical and research settings.}, } @article {pmid38011396, year = {2020}, author = {Okhovat, AA and Fatehi, F and Rafiemehr, M and Moradi, K and Kiani-Mehr, G and Nafissi, S}, title = {Evaluation of quality of life and mood disorders in caregivers of patients with amyotrophic lateral sclerosis: A single-center cross-sectional study.}, journal = {Current journal of neurology}, volume = {19}, number = {4}, pages = {190-195}, pmid = {38011396}, issn = {2717-011X}, abstract = {Background: Caregivers of patients with amyotrophic lateral sclerosis (ALS) may suffer from anxiety, depression, and reduced quality of life (QoL). Our goal was to evaluate the QoL and mood disorders in caregivers and their correlation with the patients' demographic, physical, and mental conditions. Methods: We analyzed data from 39 patients with ALS and their caregivers. Patients completed questionnaires of anxiety assessed by Generalised Anxiety Disorder Assessment (GAD-7), depression using the Beck Depression Inventory-II (BDI-II), and QoL via 40-item Amyotrophic Lateral Sclerosis Assessment Questionnaire (ALSAQ-40). Physical impairment was also measured in the patients using the revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R). Caregivers were also assessed by BDI-II, GAD-7, and 36-item Short-Form Health Survey questionnaire (SF-36). Results: The prevalence of depression and anxiety in the patients was 82.1% and 71.8%, respectively. Caregivers also had higher rates of anxiety and depression and lower levels of QoL in comparison with the general population (anxiety: 66.7%, depression: 43.6%). Depression and anxiety were considerably associated with worsened QoL in the caregivers. None of the demographic, physical, or mental characteristics of patients with ALS were related to either mood status or QoL of the caregiver population. Conclusion: Caregivers experience higher rates of anxiety and depression and lower QoL in comparison with the general population. The severity of mood disorders is inversely associated with the physical and mental domains of caregivers' QoL. Nonetheless, QoL in the caregivers is not affected by the physical or mental disability of the patients.}, } @article {pmid38396386, year = {2016}, author = {Aimo, J and Promancio, E and Damiani, PC}, title = {Determination of reducing sugars in foodstuff applying multivariate second-order calibration.}, journal = {Analytical methods : advancing methods and applications}, volume = {8}, number = {23}, pages = {4617-4631}, doi = {10.1039/c6ay00964f}, pmid = {38396386}, issn = {1759-9679}, abstract = {In the present report, a chemometrics-assisted second-order kinetic-spectrophotometric method has been developed for determining reducing sugars, glucose, fructose and lactose, in food samples, based on the reaction with hexacyanoferrate, HCF, at 70 °C in alkaline medium. A suitable experimental design helped us to establish the conditions (pH, temperature, and HCF concentration) for optimal sensitivity and selectivity among analytes. Second order data were recorded by measuring the absorbance of unreacted HCF in the spectral range of 370 to 470 nm for five minutes using a diode array. A calibration set of samples was prepared according to a central composite design containing the three sugars for training the algorithms. Validation samples containing only the analytes were prepared for checking the reliability of the algorithms. In this particular system, identical profiles for sample components are obtained in the spèctral dimension corresponding to unreacted HCF. Moreover, two kinds of interferents may be present: sample components active in the spectral region at which HCF absorbs as well as potential reducing interferents, causing linear dependence, since they provide identical profiles in spectral dimension to those of the analytes of interest. In the present work, MCR-ALS in the spectral augmentation mode was the only algorithm that could successfully resolve linear dependence. Satisfactory results were obtained by applying MCR-ALS in the spectral augmentation mode in order to achieve a second order advantage for the determination of fructose and glucose in validation samples, in test samples containing the two kinds of interferents and in real food samples, providing LODs of 4.0 and 5.0 mg L[-1], respectively. However, bad results were obtained for lactose which may be due to its low sensitivity in the augmented dimension. Good results were also obtained by applying U-PLS/RBL and N-PLS/RBL for determining simultaneously the three sugars in validation samples and in test samples containing only active spectral interferents. Finally, lactose and also, glucose and fructose, were successfully quantified in real milk samples, with LODmin = 1.0 mg L[-1], 1.0 mg L[-1] and 0.1 mg L[-1] and LODmax = 3.5, 3.8 and 4.4 mg L[-1], respectively, using UPLS/RBL, and LODmin of 1.3, 1.1 and 0.1 mg L[-1] and LODmax of 4.0, 4.3 and 4.9 mg L[-1] for lactose, glucose and fructose, respectively, for NPLS/RBL. Results for real samples in all cases were statistically comparable to those obtained by applying a reference method based on HPLC (High Performance Liquid Chromatography).}, } @article {pmid37931648, year = {2024}, author = {Aust, E and Günther, R and Hermann, A and Linse, K}, title = {[Psychologically guided group meetings for family caregivers of ALS patients].}, journal = {Fortschritte der Neurologie-Psychiatrie}, volume = {92}, number = {3}, pages = {81-89}, doi = {10.1055/a-2156-9013}, pmid = {37931648}, issn = {1439-3522}, mesh = {Humans ; *Caregivers/psychology ; Adaptation, Psychological ; *Amyotrophic Lateral Sclerosis/therapy/psychology ; Emotions ; Palliative Care ; Quality of Life/psychology ; }, abstract = {BACKGROUND: The course of amyotrophic lateral sclerosis (ALS,) associated with progressive physical limitations, is a challenge to the patients themselves and also to their family caregivers, who have to deal with psychosocial, socio-medical and organizational issues. Caregivers are often closely involved and heavily burdened themselves, which is why specific support is recommended. The aim of this study was to investigate the feasibility and acceptance of psychologically guided supportive group meetings for family caregivers in a specialist ALS outpatient clinic.

METHODS: Over a period of two years, data were collected from a total of 26 caregivers of ALS patients in order to evaluate the relevance, usefulness and criticisms of open-topic meetings that took place every three months.

RESULTS: Topics discussed in the meetings included mainly psychosocial issues such as self-care, dealing with emotions or with conflicts with the patients and third parties, as well as practical and organizational matters. The meetings were predominantly rated as helpful, well understandable and personally relevant and the exchange in a "community of destiny" was perceived as emotionally relieving.

DISCUSSION: The ALS caregiver group meetings in the described format were easy to carry out and well accepted. Supportive interventions, such as the one reported here, might be a valuable component of ALS care, to relieve the highly burdened caregivers of ALS-patients by providing them with social, emotional and practical support. However, the quantitative verification of the intervention's effectiveness is challenging - both methodologically and due to the caregivers' complex life situation. Psychosocial support services for ALS caregivers are feasible with little effort and should be an integral part of the standard ALS care based on a multi-dimensional, palliative care concept.}, } @article {pmid37930717, year = {2023}, author = {Lam, K and Cenzer, I and Levy, CR and Matlock, DD and Smith, AK and Covinsky, KE}, title = {The Natural History of Disability and Caregiving Before and After Long-Term Care Entry.}, journal = {JAMA internal medicine}, volume = {183}, number = {12}, pages = {1295-1303}, pmid = {37930717}, issn = {2168-6114}, support = {P01 AG066605/AG/NIA NIH HHS/United States ; P30 AG044281/AG/NIA NIH HHS/United States ; R03 AG074038/AG/NIA NIH HHS/United States ; KL2 TR001870/TR/NCATS NIH HHS/United States ; K24 AG068312/AG/NIA NIH HHS/United States ; }, mesh = {Aged ; Humans ; Female ; United States/epidemiology ; Aged, 80 and over ; Male ; *Long-Term Care ; *Activities of Daily Living ; Longitudinal Studies ; Medicare ; Caregivers/statistics & numerical data ; }, abstract = {IMPORTANCE: Many older persons move into long-term care facilities (LTCFs) due to disability and insufficient home caregiving options. However, the extent of disability and caregiving provided around the time of entry is unknown.

OBJECTIVE: To quantitatively describe disability and caregiving before and after LTCF entry, comparing nursing home (NH), assisted living (AL), and independent living (IL) entrants.

A longitudinal cohort study using prospectively collected annual data from the National Health and Aging Trends Study from 2011 to 2020 including participants in the continental US. Overall, 932 community-dwelling Medicare beneficiaries entering LTCF from 2011 to 2019 were included. Entry into LTCF was set as t = 0, and participant interviews from 4 years before and 2 years after were used.

MAIN OUTCOMES AND MEASURES: Prevalence of severe disability (severe difficulty or dependence in ≥3 activities of daily living), prevalence of caregivers, and median weekly caregiving hours per entrant, using weighted mixed-effects regression against time as linear spline.

RESULTS: At entry, mean (SD) age was 84 (8.4) years, 609 (64%, all percentages survey weighted) were women, 143 (6%) were Black, 29 (3%) were Hispanic, 30 (4%) were other (other race and ethnicity included American Indian, Asian, Native Hawaiian, and other), and 497 (49%) had dementia. 349 (34%) entered NH, 426 (45%) entered AL, and 157 (21%) entered IL. Overall, NH and AL entry were preceded by months of severe disability and escalating caregiving. Before entry, 49% (95% CI, 29%-68%) of NH entrants and 10% (95% CI, 3%-24%) of AL entrants had severe disability. Most (>97%) had at least a caregiver, but only one-third (NH, 33%; 95% CI, 20%-50%; AL, 33%; 95% CI, 24%-44%) had a paid caregiver. Median care was 27 hours weekly (95% CI, 18-40) in NH entrants and 18 (95% CI, 14-24) in AL entrants. On NH and AL entry, severe disability rose to 89% (95% CI, 82%-94%) and 28% (95% CI, 16%-44%) on NH and AL entry and was 66% (95% CI, 55%-75%) 2 years after entry in AL residents. Few IL entrants (<2%) had severe disability and their median care remained less than 7 hours weekly before and after entry.

CONCLUSIONS: This study found that persons often enter NHs and ALs after months of severe disability and substantial help at home, usually from unpaid caregivers. Assisted living residents move when less disabled, but approach levels of disability similar to NH entrants within 2 years. Data may help clinicians understand when home supports approach a breaking point.}, } @article {pmid37930481, year = {2024}, author = {Domi, T and Schito, P and Sferruzza, G and Russo, T and Pozzi, L and Agosta, F and Carrera, P and Riva, N and Filippi, M and Quattrini, A and Falzone, YM}, title = {Unveiling the SOD1-mediated ALS phenotype: insights from a comprehensive meta-analysis.}, journal = {Journal of neurology}, volume = {271}, number = {3}, pages = {1342-1354}, pmid = {37930481}, issn = {1432-1459}, mesh = {Humans ; Superoxide Dismutase-1/genetics ; *Amyotrophic Lateral Sclerosis/diagnosis/genetics ; Phenotype ; Genetic Testing ; Mutation ; C9orf72 Protein/genetics ; RNA-Binding Protein FUS/genetics ; }, abstract = {BACKGROUND AND OBJECTIVES: Amyotrophic lateral sclerosis associated with mutations in SOD1 (SOD1-ALS) might be susceptible to specific treatment. The aim of the study is to outline the clinical features of SOD1-ALS patients by comparing them to patients without ALS major gene variants and patients with variants in other major ALS genes. Defining SOD1-ALS phenotype may assist clinicians in identifying patients who should be prioritized for genetic testing.

METHODS: We performed an extensive literature research including original studies which reported the clinical features of SOD1-ALS and at least one of the following patient groups: C9ORF72 hexanucleotide repeat expansion (C9-ALS), TARDBP (TARDBP-ALS), FUS (FUS-ALS) or patients without a positive test for a major-ALS gene (N-ALS). A random effects meta-analytic model was applied to clinical data extracted encompassing sex, site and age of onset. To reconstruct individual patient survival data, the published Kaplan-Meier curves were digitized. Data were measured as odds ratio (OR) or standardized mean difference (SMD) as appropriate. Median survival was compared between groups.

RESULTS: Twenty studies met the inclusion criteria. We identified 721 SOD1-ALS, 470 C9-ALS, 183 TARDBP-ALS, 113 FUS-ALS and 2824 N-ALS. SOD1-ALS showed a higher rate of spinal onset compared with N-ALS and C9-ALS (OR = 4.85, 95% CI = 3.04-7.76; OR = 10.47, 95% CI = 4.32-27.87) and an earlier onset compared with N-ALS (SMD = - 0.45, 95% CI = - 0.72 to - 0.18). SOD1-ALS had a similar survival compared with N-ALS (p = 0.14), a longer survival compared with C9-ALS (p < 0.01) and FUS-ALS (p = 0.019) and a shorter survival compared with TARDBP-ALS (p < 0.01).

DISCUSSION: This study indicates the presence of a specific SOD1-ALS phenotype. Insights in SOD1-ALS clinical features are important in genetic counseling, disease prognosis and support patients' stratification in clinical trials.}, } @article {pmid37930016, year = {2023}, author = {Ahn, JJ and Miller, RH and Islam, Y}, title = {Isolation of Pure Astrocytes and Microglia from the Adult Mouse Spinal Cord For In Vitro Assays and Transcriptomic Studies.}, journal = {Journal of visualized experiments : JoVE}, volume = {}, number = {200}, pages = {}, doi = {10.3791/65893}, pmid = {37930016}, issn = {1940-087X}, support = {F31 NS117085/NS/NINDS NIH HHS/United States ; }, mesh = {Mice ; Animals ; *Microglia ; Astrocytes ; Transcriptome ; Proteomics ; Spinal Cord ; *Spinal Cord Injuries/pathology ; }, abstract = {Astrocytes and microglia play pivotal roles in central nervous system development, injury responses, and neurodegenerative diseases. These highly dynamic cells exhibit rapid responses to environmental changes and display significant heterogeneity in terms of morphology, transcriptional profiles, and functions. While our understanding of the functions of glial cells in health and disease has advanced substantially, there remains a need for in vitro, cell-specific analyses conducted in the context of insults or injuries to comprehensively characterize distinct cell populations. Isolating cells from the adult mouse offers several advantages over cell lines or neonatal animals, as it allows for the analysis of cells under pathological conditions and at specific time points. Furthermore, focusing on spinal cord-specific isolation, excluding brain involvement, enables research into spinal cord pathologies, including experimental autoimmune encephalomyelitis, spinal cord injury, and amyotrophic lateral sclerosis. This protocol presents an efficient method for isolating astrocytes and microglia from the adult mouse spinal cord, facilitating immediate or future analysis with potential applications in functional, molecular, or proteomic downstream studies.}, } @article {pmid37929431, year = {2023}, author = {Nagappa, M and Sharma, S and Govindaraj, P and Chickabasaviah, YT and Siram, R and Shroti, A and Seshagiri, DV and Debnath, M and Sinha, S and Bindu, PS and Taly, AB}, title = {Characterisation of Patients with SH3TC2 Associated Neuropathy in an Indian Cohort.}, journal = {Neurology India}, volume = {71}, number = {5}, pages = {940-945}, doi = {10.4103/0028-3886.388101}, pmid = {37929431}, issn = {1998-4022}, mesh = {Humans ; Female ; Male ; *Intracellular Signaling Peptides and Proteins/genetics ; Mutation ; Phenotype ; *Charcot-Marie-Tooth Disease/genetics ; Electrophysiological Phenomena ; }, abstract = {BACKGROUND: SH3TC2 variations lead to demyelinating recessive Charcot-Marie-Tooth (CMT) disease, which is commonly associated with early-onset scoliosis and cranial neuropathy. Data from Indian ethnicity is limited.

OBJECTIVE: We aim to report the characteristics of patients with SH3TC2-associated neuropathy from an Indian cohort.

PATIENTS AND METHODS: Data of five unrelated subjects with SH3TC2 variations were analyzed.

RESULTS: Clinical features included female predominance (n = 4), early-onset neuropathy (n = 2), pes cavus and hammer toes (n = 4), kyphoscoliosis (n = 1), impaired vision and hearing (n = 1), facial muscle weakness (n = 1), impaired kinaesthetic sense (n = 3), tremor (n = 2), and ataxia (n = 1). Four patients had the "CMT" phenotype, while one patient had Roussy-Levy syndrome. All had demyelinating electrophysiology with conduction velocities being "very slow" in one, "slow" in one, "mildly slow" in two, and "intermediate" in one patient. Brain stem auditory evoked potentials were universally abnormal though only one patient had symptomatic deafness. Seven variants were identified in SH3TC2 [homozygous = 3 (c.1412del, c.69del, c.3152G>A), heterozygous = 4 (c.1105C>T, c.3511C>T, c.2028G>C, c.254A>T)]. Except for c.3511C>T variant, the rest were novel. Three patients had additional variations in genes having pathobiological relevance in other CMTs or amyotrophic lateral sclerosis.

CONCLUSION: We provide data on a cohort of patients of Indian origin with SH3TC2 variations and highlight differences from other cohorts. Though the majority were not symptomatic for hearing impairment, evoked potentials disclosed abnormalities in all. Further studies are required to establish the functional consequences of novel variants and their interacting molecular partners identified in the present study to strengthen their association with the phenotype.}, } @article {pmid37928737, year = {2023}, author = {Johnson, GA and Krishnamoorthy, RR and Stankowska, DL}, title = {Modulating mitochondrial calcium channels (TRPM2/MCU/NCX) as a therapeutic strategy for neurodegenerative disorders.}, journal = {Frontiers in neuroscience}, volume = {17}, number = {}, pages = {1202167}, pmid = {37928737}, issn = {1662-4548}, support = {T32 AG020494/AG/NIA NIH HHS/United States ; }, abstract = {Efficient cellular communication is essential for the brain to regulate diverse functions like muscle contractions, memory formation and recall, decision-making, and task execution. This communication is facilitated by rapid signaling through electrical and chemical messengers, including voltage-gated ion channels and neurotransmitters. These messengers elicit broad responses by propagating action potentials and mediating synaptic transmission. Calcium influx and efflux are essential for releasing neurotransmitters and regulating synaptic transmission. Mitochondria, which are involved in oxidative phosphorylation, and the energy generation process, also interact with the endoplasmic reticulum to store and regulate cytoplasmic calcium levels. The number, morphology, and distribution of mitochondria in different cell types vary based on energy demands. Mitochondrial damage can cause excess reactive oxygen species (ROS) generation. Mitophagy is a selective process that targets and degrades damaged mitochondria via autophagosome-lysosome fusion. Defects in mitophagy can lead to a buildup of ROS and cell death. Numerous studies have attempted to characterize the relationship between mitochondrial dysfunction and calcium dysregulation in neurodegenerative diseases such as Alzheimer's Disease, Parkinson's Disease, Huntington's Disease, Amyotrophic lateral sclerosis, spinocerebellar ataxia, and aging. Interventional strategies to reduce mitochondrial damage and accumulation could serve as a therapeutic target, but further research is needed to unravel this potential. This review offers an overview of calcium signaling related to mitochondria in various neuronal cells. It critically examines recent findings, exploring the potential roles that mitochondrial dysfunction might play in multiple neurodegenerative diseases and aging. Furthermore, the review identifies existing gaps in knowledge to guide the direction of future research.}, } @article {pmid37928442, year = {2023}, author = {Chen, SK and Hawley, ZCE and Zavodszky, MI and Hana, S and Ferretti, D and Grubor, B and Hawes, M and Xu, S and Hamann, S and Marsh, G and Cullen, P and Challa, R and Carlile, TM and Zhang, H and Lee, WH and Peralta, A and Clarner, P and Wei, C and Koszka, K and Gao, F and Lo, SC}, title = {Efficacy and safety of a SOD1-targeting artificial miRNA delivered by AAV9 in mice are impacted by miRNA scaffold selection.}, journal = {Molecular therapy. Nucleic acids}, volume = {34}, number = {}, pages = {102057}, pmid = {37928442}, issn = {2162-2531}, abstract = {Toxic gain-of-function mutations in superoxide dismutase 1 (SOD1) contribute to approximately 2%-3% of all amyotrophic lateral sclerosis (ALS) cases. Artificial microRNAs (amiRs) delivered by adeno-associated virus (AAV) have been proposed as a potential treatment option to silence SOD1 expression and mitigate disease progression. Primary microRNA (pri-miRNA) scaffolds are used in amiRs to shuttle a hairpin RNA into the endogenous miRNA pathway, but it is unclear whether different primary miRNA (pri-miRNA) scaffolds impact the potency and safety profile of the expressed amiR in vivo. In our process to develop an AAV amiR targeting SOD1, we performed a preclinical characterization of two pri-miRNA scaffolds, miR155 and miR30a, sharing the same guide strand sequence. We report that, while the miR155-based vector, compared with the miR30a-based vector, leads to a higher level of the amiR and more robust suppression of SOD1 in vitro and in vivo, it also presents significantly greater risks for CNS-related toxicities in vivo. Despite miR30a-based vector showing relatively lower potency, it can significantly delay the development of ALS-like phenotypes in SOD1-G93A mice and increase survival in a dose-dependent manner. These data highlight the importance of scaffold selection in the pursuit of highly efficacious and safe amiRs for RNA interference gene therapy.}, } @article {pmid37926865, year = {2024}, author = {Xiao, X and Li, M and Ye, Z and He, X and Wei, J and Zha, Y}, title = {FUS gene mutation in amyotrophic lateral sclerosis: a new case report and systematic review.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {25}, number = {1-2}, pages = {1-15}, doi = {10.1080/21678421.2023.2272170}, pmid = {37926865}, issn = {2167-9223}, mesh = {Humans ; Male ; *Amyotrophic Lateral Sclerosis/diagnosis/genetics ; Mutation/genetics ; Mutation, Missense ; *Neurodegenerative Diseases ; Retrospective Studies ; RNA-Binding Protein FUS/genetics ; }, abstract = {OBJECTIVE: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease associated with upper and lower motor neuron degeneration and necrosis, characterized by progressive muscle weakness, atrophy, and paralysis. The FUS mutation-associated ALS has been classified as ALS6. We reported a case of ALS6 with de novo mutation and investigated retrospectively the characteristics of cases with FUS mutation.

METHODS: We reported a male patient with a new heterozygous variant of the FUS gene and comprehensively reviewed 173 ALS cases with FUS mutation. The literature was reviewed from the PubMed MEDLINE electronic database (https://www.ncbi.nlm.nih.gov/pubmed) using "Amyotrophic Lateral Sclerosis and Fus mutation" or "Fus mutation" as key words from 1 January 2009 to 1 January 2022.

RESULTS: We report a case of ALS6 with a new mutation point (c.1225-1227delGGA) and comprehensively review 173 ALS cases with FUS mutation. Though ALS6 is all with FUS mutation, it is still a highly heterogenous subtype. The average onset age of ALS6 is 35.2 ± 1.3 years, which is much lower than the average onset age of ALS (60 years old). Juvenile FUS mutations have an aggressive progression of disease, with an average time from onset to death or tracheostomy of 18.2 ± 0.5 months. FUS gene has the characteristics of early onset, faster progress, and shorter survival, especially in deletion mutation p.G504Wfs *12 and missense mutation of p.P525L.

CONCLUSIONS: ALS6 is a highly heterogenous subtype. Our study could allow clinicians to better understand the non-ALS typical symptoms, phenotypes, and pathophysiology of ALS6.}, } @article {pmid37924056, year = {2023}, author = {Sun, J and Chen, J and Xie, Q and Sun, M and Zhang, W and Wang, H and Liu, N and Wang, Q and Wang, M}, title = {Sodium butyrate alleviates R97-116 peptide-induced myasthenia gravis in mice by improving the gut microbiota and modulating immune response.}, journal = {Journal of inflammation (London, England)}, volume = {20}, number = {1}, pages = {37}, pmid = {37924056}, issn = {1476-9255}, abstract = {Fermented butyrate exhibits an anti-inflammatory response to maintain immune homeostasis within the gut. However, the effect and underlying mechanism of butyrate on myasthenia gravis (MG) remain unclear. The changes in the gut microbiota and fecal contents of SCFAs in MG patients were examined. R97-116 peptide was used to induce the experimental autoimmune myasthenia gravis (EAMG) mice and sodium butyrate (NaB) was gavaged to the EAMG mice. Gut microbiota, the frequency of Th1, Th17, Treg, Tfh, and B cells, the levels of IFN-γ, IL-17 A, IL-10, IL-21, and anti-R97-116 IgG, RNA-seq of total B cells in the spleen were explored by metagenomics, flow cytometry, ELISA, and transcriptomics. A significant reduction in SCFA-producing bacteria including Butyricimonas synergistica and functional modules including butyrate synthesis/production II was observed in MG patients and fecal SCFAs detection confirmed the increase. The EAMG mice were successfully constructed and NaB supplementation has changed the composition and function of the gut microbiota. The numbers of Th1, Th17, Tfh, and B cells were significantly increased while that of Treg cells was obviously decreased in EAMG mice compared with controls. Interestingly, NaB treatment has reduced the amounts of Th17, Tfh, and B cells but increased that of Treg cells. Accordingly, the levels of IL-17 A, IL-21, and IgG were increased while IL-10 was decreased in EAMG mice. However, NaB treatment reduced IL-17 A and IL-21 but increased that of IL-10. RNA-seq of B cells has revealed 4577 deferentially expressed genes (DEGs), in which 1218 DEGs were up-regulated while 3359 DEGs were down-regulated in NaB-treated EAMG mice. GO enrichment and KEGG pathway analysis unveiled that the function of these DEGs was mainly focused on immunoglobulin production, mitochondrial respiratory chain complex, ribosome, oxidative phosphorylation, and CNS diseases including amyotrophic lateral sclerosis. We have found that butyrate was significantly reduced in MG patients and NaB gavage could evidently improve MG symptoms in EAMG mice by changing the gut microbiota, regulating the immune response, and altering the gene expression and function of B cells, suggesting NaB might be a potential immunomodulatory supplement for MG drugs.}, } @article {pmid37922093, year = {2024}, author = {Jellinger, KA}, title = {Understanding depression with amyotrophic lateral sclerosis: a short assessment of facts and perceptions.}, journal = {Journal of neural transmission (Vienna, Austria : 1996)}, volume = {131}, number = {2}, pages = {107-115}, pmid = {37922093}, issn = {1435-1463}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/complications/therapy/diagnosis ; Depression/complications ; Quality of Life ; Affect ; *Neurodegenerative Diseases/complications ; }, abstract = {Depression with an average prevalence of 25-40% is a serious condition in amyotrophic lateral sclerosis (ALS) that can impact quality of life and survival of patients and caregiver burden, yet the underlying neurobiology is poorly understood. Preexisting depression has been associated with a higher risk of developing ALS, while people with ALS have a significantly higher risk of developing depression that can cause multiple complications. Depression may be a prodromal or subclinical symptom prior to motor involvement, although its relations with disease progression and impairment of quality of life are under discussion. Unfortunately, there are no studies existing that explore the pathogenic mechanisms of depression associated with the basic neurodegenerative process, and no specific neuroimaging data or postmortem findings for the combination of ALS and depression are currently available. Experience from other neurodegenerative processes suggests that depressive symptoms in ALS may be the consequence of cortical thinning in prefrontal regions and other cortex areas, disruption of mood-related brain networks, dysfunction of neurotransmitter systems, changing cortisol levels and other, hitherto unknown mechanisms. Treatment of both ALS and depression is a multidisciplinary task, depression generally being treated with a combination of antidepressant medication, physiotherapy, psychological and other interventions, while electroconvulsive therapy and deep brain stimulation might not be indicated in the majority of patients in view of their poor prognosis. Since compared to depression in other neurodegenerative diseases, our knowledge of its molecular basis in ALS is missing, multidisciplinary clinicopathological studies to elucidate the pathomechanism of depression in motor system disorders including ALS are urgently warranted.}, } @article {pmid37920668, year = {2023}, author = {Ho, WY and Chak, LL and Hor, JH and Liu, F and Diaz-Garcia, S and Chang, JC and Sanford, E and Rodriguez, MJ and Alagappan, D and Lim, SM and Cho, YL and Shimizu, Y and Sun, AX and Tyan, SH and Koo, E and Kim, SH and Ravits, J and Ng, SY and Okamura, K and Ling, SC}, title = {FUS-dependent microRNA deregulations identify TRIB2 as a druggable target for ALS motor neurons.}, journal = {iScience}, volume = {26}, number = {11}, pages = {108152}, pmid = {37920668}, issn = {2589-0042}, abstract = {MicroRNAs (miRNAs) modulate mRNA expression, and their deregulation contributes to various diseases including amyotrophic lateral sclerosis (ALS). As fused in sarcoma (FUS) is a causal gene for ALS and regulates biogenesis of miRNAs, we systematically analyzed the miRNA repertoires in spinal cords and hippocampi from ALS-FUS mice to understand how FUS-dependent miRNA deregulation contributes to ALS. miRNA profiling identified differentially expressed miRNAs between different central nervous system (CNS) regions as well as disease states. Among the up-regulated miRNAs, miR-1197 targets the pro-survival pseudokinase Trib2. A reduced TRIB2 expression was observed in iPSC-derived motor neurons from ALS patients. Pharmacological stabilization of TRIB2 protein with a clinically approved cancer drug rescues the survival of iPSC-derived human motor neurons, including those from a sporadic ALS patient. Collectively, our data indicate that miRNA profiling can be used to probe the molecular mechanisms underlying selective vulnerability, and TRIB2 is a potential therapeutic target for ALS.}, } @article {pmid37920473, year = {2023}, author = {Lemos, JP and Tenório, LPG and Mouly, V and Butler-Browne, G and Mendes-da-Cruz, DA and Savino, W and Smeriglio, P}, title = {T cell biology in neuromuscular disorders: a focus on Duchenne Muscular Dystrophy and Amyotrophic Lateral Sclerosis.}, journal = {Frontiers in immunology}, volume = {14}, number = {}, pages = {1202834}, pmid = {37920473}, issn = {1664-3224}, mesh = {Humans ; *Muscular Dystrophy, Duchenne/therapy ; *Amyotrophic Lateral Sclerosis/therapy/genetics ; *Neuromuscular Diseases ; Muscles ; Genetic Therapy/methods ; }, abstract = {Growing evidence demonstrates a continuous interaction between the immune system, the nerve and the muscle in neuromuscular disorders of different pathogenetic origins, such as Duchenne Muscular Dystrophy (DMD) and Amyotrophic Lateral Sclerosis (ALS), the focus of this review. Herein we highlight the complexity of the cellular and molecular interactions involving the immune system in neuromuscular disorders, as exemplified by DMD and ALS. We describe the distinct types of cell-mediated interactions, such as cytokine/chemokine production as well as cell-matrix and cell-cell interactions between T lymphocytes and other immune cells, which target cells of the muscular or nervous tissues. Most of these interactions occur independently of exogenous pathogens, through ligand-receptor binding and subsequent signal transduction cascades, at distinct levels of specificity. Although this issue reveals the complexity of the system, it can also be envisioned as a window of opportunity to design therapeutic strategies (including synthetic moieties, cell and gene therapy, as well as immunotherapy) by acting upon one or more targets. In this respect, we discuss ongoing clinical trials using VLA-4 inhibition in DMD, and in ALS, with a focus on regulatory T cells, both revealing promising results.}, } @article {pmid37920145, year = {2024}, author = {Stamatelatou, A and Bertinetto, CG and Jansen, JJ and Postma, G and Selnaes, KM and Bathen, TF and Heerschap, A and Scheenen, TWJ and , }, title = {A multivariate curve resolution analysis of multicenter proton spectroscopic imaging of the prostate for cancer localization and assessment of aggressiveness.}, journal = {NMR in biomedicine}, volume = {37}, number = {3}, pages = {e5062}, doi = {10.1002/nbm.5062}, pmid = {37920145}, issn = {1099-1492}, support = {813120//European Union's Horizon 2020 research and innovation program/ ; }, mesh = {Male ; Humans ; *Prostate/diagnostic imaging/pathology ; Protons ; *Prostatic Neoplasms/diagnostic imaging ; Magnetic Resonance Imaging ; Magnetic Resonance Spectroscopy/methods ; Least-Squares Analysis ; }, abstract = {In this study, we investigated the potential of the multivariate curve resolution alternating least squares (MCR-ALS) algorithm for analyzing three-dimensional (3D) [1] H-MRSI data of the prostate in prostate cancer (PCa) patients. MCR-ALS generates relative intensities of components representing spectral profiles derived from a large training set of patients, providing an interpretable model. Our objectives were to classify magnetic resonance (MR) spectra, differentiating tumor lesions from benign tissue, and to assess PCa aggressiveness. We included multicenter 3D [1] H-MRSI data from 106 PCa patients across eight centers. The patient cohort was divided into a training set (N = 63) and an independent test set (N = 43). Singular value decomposition determined that MR spectra were optimally represented by five components. The profiles of these components were extracted from the training set by MCR-ALS and assigned to specific tissue types. Using these components, MCR-ALS was applied to the test set for a quantitative analysis to discriminate tumor lesions from benign tissue and to assess tumor aggressiveness. Relative intensity maps of the components were reconstructed and compared with histopathology reports. The quantitative analysis demonstrated a significant separation between tumor and benign voxels (t-test, p < 0.001). This result was achieved including voxels with low-quality MR spectra. A receiver operating characteristic analysis of the relative intensity of the tumor component revealed that low- and high-risk tumor lesions could be distinguished with an area under the curve of 0.88. Maps of this component properly identified the extent of tumor lesions. Our study demonstrated that MCR-ALS analysis of [1] H-MRSI of the prostate can reliably identify tumor lesions and assess their aggressiveness. It handled multicenter data with minimal preprocessing and without using prior knowledge or quality control. These findings indicate that MCR-ALS can serve as an automated tool to assess the presence, extent, and aggressiveness of tumor lesions in the prostate, enhancing diagnostic capabilities and treatment planning of PCa patients.}, } @article {pmid37919089, year = {2023}, author = {Moda, F and Ciullini, A and Dellarole, IL and Lombardo, A and Campanella, N and Bufano, G and Cazzaniga, FA and Giaccone, G}, title = {Secondary Protein Aggregates in Neurodegenerative Diseases: Almost the Rule Rather than the Exception.}, journal = {Frontiers in bioscience (Landmark edition)}, volume = {28}, number = {10}, pages = {255}, doi = {10.31083/j.fbl2810255}, pmid = {37919089}, issn = {2768-6698}, mesh = {Humans ; Aged ; *Neurodegenerative Diseases/pathology ; Protein Aggregates ; *Lewy Body Disease/metabolism/pathology ; *Synucleinopathies ; *Alzheimer Disease/metabolism ; *Parkinson Disease/metabolism ; tau Proteins/metabolism ; *Prion Diseases ; Amyloid beta-Peptides ; *Frontotemporal Lobar Degeneration ; }, abstract = {The presence of protein aggregates is a hallmark of many neurodegenerative diseases, including Parkinson's disease (PD), Alzheimer's disease (AD), and frontotemporal lobar degeneration (FTLD). Traditionally, each disease has been associated with the aggregation of specific proteins, which serve as disease-specific biomarkers. For example, aggregates of α-synuclein (α-syn) are found in α-synucleinopathies such as PD, dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). Similarly, AD is characterized by aggregates of amyloid-beta (Aβ) and tau proteins. However, it has been observed that these protein aggregates can also occur in other neurodegenerative diseases, contributing to disease progression. For instance, α-syn aggregates have been detected in AD, Down syndrome, Huntington's disease, prion diseases, and various forms of FTLD. Similarly, Aβ aggregates have been found in conditions like DLB and PD. Tau aggregates, in addition to being present in primary tauopathies, have been identified in prion diseases, α-synucleinopathies, and cognitively healthy aged subjects. Finally, aggregates of TDP-43, typically associated with FTLD and amyotrophic lateral sclerosis (ALS), have been observed in AD, progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), MSA, DLB, and other neurodegenerative diseases. These findings highlight the complexity of protein aggregation in neurodegeneration and suggest potential interactions and common mechanisms underlying different diseases. A deeper understating of this complex scenario may eventually lead to the identification of a better elucidation of the pathogenetic mechanisms of these devastating conditions and hopefully new therapeutic stragegies.}, } @article {pmid37918554, year = {2023}, author = {Mishra, D and Narain, P and Dave, U and Gomes, J}, title = {Role of ALS-associated OPTN-K489E mutation in neuronal cell-death regulation.}, journal = {Molecular and cellular neurosciences}, volume = {127}, number = {}, pages = {103904}, doi = {10.1016/j.mcn.2023.103904}, pmid = {37918554}, issn = {1095-9327}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism ; *Neuroblastoma ; Mutation ; Cell Death ; Apoptosis/genetics ; }, abstract = {Optineurin (OPTN) gene is a marker of amyotrophic lateral sclerosis (ALS). However, the role of optineurin protein (OPTN) in ALS pathology is unclear, even though it is known to regulate autophagy, apoptosis, and other survival-death cellular processes. Genetic analysis of Indian ALS patients by our group ascertained a novel mutation K489E in the OPTN gene. To identify the molecular mechanism associated with OPTN and its mutation, we developed an in-vitro cell model using SH-SY5Y cells harbouring OPTN and OPTN-K489E mutation along with its control vector. Since we observed a significant decrease in cell viability in the mutant, we measured the expressions of genes and proteins mediating apoptosis, necroptosis, and autophagy, to establish the role of OPTN in cell death regulation. Our results show that OPTN-K489E mutation changes the relative gene expressions of miRNA-9, REST, CoREST and BDNF, and causes apoptosis. We also observed an up-regulation in the expressions of necroptosis mediated genes RIPK1, RIPK3, and MLKL and autophagy mediated genes TBK1, P62, and LC3II. The results of FACS analyses revealed that this mutation promotes apoptotic and necroptotic processes confirming the pathogenicity of OPTN-K489E.}, } @article {pmid37916886, year = {2024}, author = {Tang, L and Tang, X and Zhao, Q and Li, Y and Bu, Y and Liu, Z and Li, J and Guo, J and Shen, L and Jiang, H and Tang, B and Xu, R and Cao, W and Yuan, Y and Wang, J}, title = {Mutation and clinical analysis of the CLCC1 gene in amyotrophic lateral sclerosis patients from Central South China.}, journal = {Annals of clinical and translational neurology}, volume = {11}, number = {1}, pages = {79-88}, pmid = {37916886}, issn = {2328-9503}, support = {2021YFA0805202//National Key Research and Development Program of China/ ; 81300981//National Natural Science Foundation of China/ ; 81671120//National Natural Science Foundation of China/ ; 82171431//National Natural Science Foundation of China/ ; 2020LNJJ13//the Project Program of National Clinical Research Center for Geriatric Disorders at Xiangya Hospital/ ; STI2030 Major Projects 2021ZD0201803//the Science and Technology Innovation 2030/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics ; Mutation ; Mutation, Missense ; Genetic Association Studies ; China ; Chloride Channels/genetics ; }, abstract = {INTRODUCTION: Recently, chloride channel CLIC-like 1 (CLCC1) was reported to be a novel ALS-related gene. We aimed to screen CLCC1 variants in our ALS cohort and further explore the genotype-phenotype correlation of CLCC1-related ALS.

METHODS: We screened rare damaging variants in CLCC1 from our cohorts of 1005 ALS patients and 1224 healthy controls with whole-exome sequencing in Central South China. Fisher's exact test was conducted for association analysis at the entire gene level and single variant level.

RESULTS: In total, four heterozygous missense variants in CLCC1 were identified from four unrelated sporadic ALS patients and predicted to be putative pathogenic by in silico tools and protein model prediction, accounting for 0.40% of all patients (4/1005). The four variants were c.A275C (p.Q92P), c.G1139A (p.R380K), c.C1244T (p.T415M), and c.G1328A (p.R443Q), respectively, which had not been reported in ALS patients previously. Three of four variants were located in exon 10. Patients harboring CLCC1 variants seemed to share a group of similar clinical features, including earlier age at onset, rapid progression, spinal onset, and vulnerable cognitive status. Statistically, we did not find CLCC1 to be associated with the risk of ALS at the entire gene level or single variant level.

CONCLUSION: Our findings further expanded the genetic and clinical spectrum of CLCC1-related ALS and provided more genetic evidence for anion channel involvement in the pathogenesis of ALS, but further investigations are needed to verify our findings.}, } @article {pmid37915644, year = {2023}, author = {Kassahun Bekele, B and Kwizera, L and Abdul Razzak, R and Alfadul, ESA and Anand, A and Wojtara, M and Nazir, A and Uwishema, O}, title = {ALS in Africa: current knowledge and exciting opportunities for future study - short communication.}, journal = {Annals of medicine and surgery (2012)}, volume = {85}, number = {11}, pages = {5827-5830}, pmid = {37915644}, issn = {2049-0801}, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that can present with motor and extra-motor manifestations. Its global prevalence is 4.42 per 1 000 000, and it has a high mortality rate. In sub-Saharan Africa alone, 15 per 100 000 develop ALS mainly between their 40s and 60s and only one-fourth of them have access to treatment. ALS was found to be not only affected by genetic variation but also by the patient's mood and lifestyle. In Africa, males and younger people tend to be affected with ALS and rarely present with bulbar onset. ALS diagnosis is very challenging due to the lack of ALS-specific biomarkers and the sharing of some clinical features with other syndromes. ALS treatment is mainly riluzole and supportive treatment via nasogastric tube and ventilatory support. The access to treatment in Africa is very limited, thus a very bad prognosis with a median survival time of 14 months post-diagnosis. Further research is needed to assess the real situation in Africa and to try to closely monitor patients suffering from ALS.}, } @article {pmid37915239, year = {2024}, author = {Lee, J and Yoon, D and Sung, KW and Bae, EJ and Park, DH and Suh, YH and Kwon, YT}, title = {Targeted degradation of SNCA/α-synuclein aggregates in neurodegeneration using the AUTOTAC chemical platform.}, journal = {Autophagy}, volume = {20}, number = {2}, pages = {463-465}, pmid = {37915239}, issn = {1554-8635}, mesh = {Mice ; Animals ; *alpha-Synuclein/metabolism ; Autophagy/physiology ; Ligands ; *Parkinson Disease/metabolism ; Brain/metabolism ; }, abstract = {Parkinson disease (PD) characterized by dopaminergic neuronal loss is caused by aggregation of misfolded SNCA/α-synuclein. We recently developed autophagy-targeting chimera (AUTOTAC), a targeted protein degradation (TPD) technology based on the macroautophagy/autophagy-lysosome pathway (ALP). In this study, we employed AUTOTAC to synthesize ATC161, a chimeric compound that adopts Anle138b as target-binding ligand (TBL) for SNCA aggregates. The autophagy-targeting ligand (ATL) of ATC161 was designed to allosterically activate the autophagy receptor SQSTSM1/p62 (sequestosome 1), a key step for targeting SNCA aggregates to the phagophore. The lysosomal degradation of SNCA aggregates by ATC161 acutely occurs at DC50 of 100-500 nM with no significant off-target degradation of monomeric SNCA. ATC161 protects cells from DNA and mitochondrial damage by SNCA aggregates. In PD model mice, oral administration of ATC161 decreases the level of SNCA aggregates and their propagation across brain regions, which mitigates glial inflammatory responses and improves muscle strength and locomotive activity. An Investigational New Drug (IND) was approved by the Korean Food and Drug Administration for a phase 1 clinical trial to treat PD, Alzheimer disease (AD), progressive supranuclear palsy (PSP), and amyotrophic lateral sclerosis (ALS). We suggest that AUTOTAC provides a platform for drug discovery in proteinopathies and other diseases.}, } @article {pmid37914747, year = {2023}, author = {Sung, W and Kim, JA and Kim, YS and Park, J and Oh, KW and Sung, JJ and Ki, CS and Kim, YE and Kim, SH}, title = {An analysis of variants in TARDBP in the Korean population with amyotrophic lateral sclerosis: comparison with previous data.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {18805}, pmid = {37914747}, issn = {2045-2322}, mesh = {Humans ; Middle Aged ; *Amyotrophic Lateral Sclerosis/epidemiology/genetics/pathology ; Cohort Studies ; Genetic Testing ; Mutation ; Mutation, Missense ; Republic of Korea/epidemiology ; }, abstract = {The TARDBP gene variant is a known major cause of amyotrophic lateral sclerosis (ALS), with limited reports of Korean patients with ALS harboring the variants in TARDBP. This large cohort study introduces four ALS patients who share the p.M337V variant of the TARDBP, allowing for an investigation of clinical characteristics and prognosis by analyzing previously reported cases with the same variant. From November 2014 to August 2022, participants were recruited from two tertiary hospitals in Seoul, Korea. Clinical characteristics of patients diagnosed with ALS carrying the variant in TARDBP were evaluated. Previous articles demonstrating subjects' characteristics were reviewed. Four patients were identified with the pathogenic missense variant (c.1009A>G; p.M337V) in the TARDBP. The mean age of onset was 55 years old, and none of the patients showed severe cognitive impairment. Sixty-three patients carrying the p.M337V variant in TARDBP from this study and previous reports delineated young age of onset (51.6 years), high frequency of bulbar onset patients (61.9%), and low comorbidity of frontotemporal dementia. This study reveals the presence of pathogenic variant of TARDBP in Korea and emphasizes the importance of genetic screening of the TARDBP gene, in diagnosing ALS and evaluating prognosis among familial and simplex ALS patients in Korea.}, } @article {pmid37913752, year = {2023}, author = {Chou, PY and Chen, CM and Wang, CC and Tai, CJ and Lin, YK and Tang, YJ}, title = {Characteristics and Effects of Chinese Herbal Medicine in the Management of Female Infertility: A Hospital-Based Study.}, journal = {Complementary medicine research}, volume = {30}, number = {6}, pages = {481-491}, doi = {10.1159/000534590}, pmid = {37913752}, issn = {2504-2106}, mesh = {Humans ; Female ; Retrospective Studies ; *Drugs, Chinese Herbal/therapeutic use ; *Infertility, Female/therapy ; Treatment Outcome ; Hospitals ; }, abstract = {BACKGROUND: In Taiwan, Chinese herbal medicine (CHM) is used to treat female infertility. Evidence indicates that the absence of monotherapy efficacy assessment and comparison with mainstream interventions may lead to the improper use of CHM for female infertility.

METHODS: A retrospective cohort study enrolled female patients at a hospital undergoing CHM intervention to treat infertility from 2012 to 2020 in order to determine the outcomes of CHM monotherapy for female infertility. Kaplan-Meier analysis under strict assumptions was used to estimate the cumulative probability of pregnancy and live births after CHM. Cox hazard regression analysis was used to estimate the hazard ratios of prognostic variables, namely, the woman's age and diagnostic category.

RESULTS: 694 women met the inclusion criteria and accounted for 2,145 cycles. A total of 190 pregnancies resulted in 125 live births, all of which were singleton births of babies with 16 perinatal complications requiring hospitalization. The real cumulative pregnancy rate and cumulative live birth rate (CLBR) for the total population after 10 cycles were between 27.4% and 35.2% and between 18% and 22.1%, respectively. Compared with the live birth rate corresponding to patients aged under 35 years, that of older patients, particularly those aged 38-39 years, was significantly lower (hazard ratio: 0.19, 95% confidence interval: 0.11-0.33). Women with other diagnoses, namely, uterine problems or endometriosis, had a greater probability of a live birth than did women with tubal pathology (hazard ratio: 6.31, 95% confidence interval: 1.99-20.07).

CONCLUSION: To the best of our knowledge, this is the first retrospective study to employ life table analysis to determine the CHM treatment outcomes in terms of female infertility. The study established a basis to compare in vitro fertilization (IVF) with CHM and identified the advantages and disadvantages of CHM for treating female infertility. Although the CLBR of present study is lower than those reported in IVF studies, CHM in treating female infertility can still be beneficial to women aged younger than 38 years or with diagnoses other than tubal pathology and worth recommendation by reproductive specialists according to the promising results gained from the strict criteria. However, in order to determine the optimal timing, possible mechanism, corresponding side effects, and the efficacy of CHM combined with IVF for treating female infertility, rigorous research is required.

UNLABELLED: HintergrundIn Taiwan wird die chinesische Heilpflanzenmedizin (CHM) zur Behandlung weiblicher Infertilität angewendet. Es liegen Hinweise vor, nach denen fehlende Wirksamkeitsbeurteilungen der Monotherapien und Vergleiche mit herkömmlichen Interventionen zu einer unsachgemäßen Anwendung von CHM bei weiblicher Infertilität führen können.MethodenEine retrospektive Kohortenstudie schloss Patientinnen eines Krankenhauses ein, die von 2012 bis 2020 wegen Infertilität mit CHM behandelt wurden, um die Behandlungsergebnisse der CHM-Monotherapie bei weiblicher Infertilität zu ermitteln. Zur Schätzung der kumulativen Wahrscheinlichkeit von Schwangerschaften und Lebendgeburten nach einer CHM-Behandlung wurde die Kaplan-Meier-Analyse unter strengen Annahmen verwendet. Mit Hilfe der Cox-Hazard-Regressionsanalyse wurden die Risikoverhältnisse der prognostischen Variablen Alter der Frau und Diagnosekategorie geschätzt.Ergebnisse694 Frauen erfüllten die Einschlusskriterien und die Zahl der Zyklen betrug 2,145. Insgesamt 190 Schwangerschaften führten zu 125 Lebendgeburten, allesamt Einlingsgeburten, mit 16 perinatalen Komplikationen, die eine Hospitalisierung erforderten. Die reale kumulative Schwangerschaftsrate und die kumulative Lebendgeburtenrate (cumulative live birth rate, CLBR) für die Gesamtpopulation nach 10 Zyklen lagen zwischen 27.4% und 35.2% bzw. zwischen 18% und 22.1%. Die Lebendgeburtenrate bei älteren Patientinnen, insbesondere im Alter von 38 bis 39 Jahren, war deutlich niedriger als bei Patientinnen unter 35 Jahren (Hazard Ratio: 0.19, 95%-Konfidenzintervall: 0.11–0.33). Bei Frauen mit anderen Diagnosen wie Gebärmutterproblemen oder Endometriose war die Wahrscheinlichkeit einer Lebendgeburt höher als bei Frauen mit Eileitererkrankungen (Hazard Ratio: 6.31, 95%-Konfidenzintervall: 1.99–20.07).SchlussfolgerungUnseres Wissens ist dies die erste retrospektive Studie, in der die Ergebnisse der CHM-Behandlung bei weiblicher Infertilität mittels Sterbetafelanalyse ermittelt wurden. Die Studie bildet eine Grundlage für den Vergleich von In-vitro-Fertilisation (IVF) mit CHM und zeigt die Vor- und Nachteile der CHM zur Behandlung weiblicher Infertilität auf. Zwar fällt die kumulative Lebendgeburtenrate in der vorliegenden Studie niedriger aus als in IVF-Studien, doch kann die CHM bei der Behandlung weiblicher Infertilität für Frauen unter 38 Jahren oder Frauen, die eine andere Diagnose als eine Eileitererkrankung haben, von Nutzen sein und angesichts der vielversprechenden Ergebnisse, die aus den strengen Kriterien gewonnen wurden, ist sie eine Empfehlung durch Reproduktionsspezialisten wert. Allerdings sind rigorose Forschungsarbeiten erforderlich, um die optimale Zeitplanung, den möglichen Mechanismus, die entsprechenden Nebenwirkungen und die Wirksamkeit der CHM in Kombination mit IVF zur Behandlung der weiblichen Infertilität zu ermitteln.}, } @article {pmid37910649, year = {2025}, author = {Franklin, JE}, title = {Palliative hypnosis approaches in the symptomatic treatment of amyotrophic lateral sclerosis (ALS).}, journal = {The American journal of clinical hypnosis}, volume = {67}, number = {1}, pages = {54-68}, doi = {10.1080/00029157.2023.2252875}, pmid = {37910649}, issn = {2160-0562}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy/psychology ; *Palliative Care/methods ; *Hypnosis/methods ; Male ; Middle Aged ; Aged ; Female ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a rare, incurable, and ultimately fatal, devastating, progressive degenerative neurologic disease. It causes upheaval in the lives of patients and family caregivers alike. Palliative care can play an important supportive role in the care of patients and families dealing with the devastation of this illness. Clinical hypnosis has demonstrated benefits in treating the symptoms associated with severe chronic illness. There are, however, few studies looking at the benefits of clinical hypnosis in treating the symptom burden of ALS. This article describes palliative care and how it can provide an additional layer of support to seriously ill patients. A brief review of previous studies of hypnosis in the supportive, symptomatic treatment of ALS is provided, followed by a description of a case series of 30 Veterans who received clinical hypnosis and self-hypnosis training as a complementary treatment for the symptoms of ALS. Details of three case histories are included to highlight and discuss specific strategies and emblematic clinical responses. There is evidence that clinical hypnosis can benefit ALS patients and family caregivers struggling with this devastating illness.}, } @article {pmid37910562, year = {2023}, author = {Lugg, A and Schindle, M and Sivak, A and Tankisi, H and Jones, KE}, title = {Nerve excitability measured with the TROND protocol in amyotrophic lateral sclerosis: a systematic review and meta-analysis.}, journal = {Journal of neurophysiology}, volume = {130}, number = {6}, pages = {1480-1491}, doi = {10.1152/jn.00174.2023}, pmid = {37910562}, issn = {1522-1598}, support = {RGPIN-2017-05624//Gouvernement du Canada | Natural Sciences and Engineering Research Council of Canada (NSERC)/ ; }, mesh = {Humans ; Action Potentials/physiology ; *Amyotrophic Lateral Sclerosis ; Axons/physiology ; Biomarkers ; Prospective Studies ; Clinical Protocols ; }, abstract = {This meta-analysis assessed the 30+ nerve excitability indices generated by the TROND protocol to identify potential biomarkers for amyotrophic lateral sclerosis (ALS). A comprehensive search was conducted in multiple databases to identify human studies that tested median motor axons. Forest plot analyses were performed using a random-effects model to determine the pooled effect (Z-score), heterogeneity (I[2]), and Cohen's d for potential biomarker identification. Out of 2,866 studies, 23 studies met the inclusion criteria, incorporating data from 719 controls and 942 patients with ALS. Seven indices emerged as potential biomarkers: depolarizing threshold electrotonus (TEd) 90-100 ms, strength-duration time constant (SDTC), superexcitability, TEd 40-60 ms, resting I/V slope, 50% depolarizing I/V, and subexcitability (ranked by the magnitude of the difference between patients and controls from largest to smallest). In a sensitivity analysis focusing on patients with larger compound muscle action potentials (CMAPs), only four indices were potential biomarkers: TEd 10-20 ms, TEd 90-100 ms, superexcitability, and SDTC. Among the extensive range of 30+ excitability indices generated by the TROND protocol, we have identified seven indices that effectively differentiate patients with ALS from healthy controls. Furthermore, a smaller subset of four indices shows promise as potential biomarkers when the CMAP remains relatively large. However, most studies were considered to be at moderate risk of bias due to case-control designs and absence of sensitivity and specificity calculations, underscoring the need for more prospective diagnostic test-accuracy studies with appropriate disease controls.NEW & NOTEWORTHY This meta-analysis uncovers seven potential axonal excitability biomarkers for lower motor neuron pathology in ALS, shedding light on ion channel dysfunction. The identified dysfunction aligns with the primary pathology-protein homeostasis disruption. These biomarkers could fill a gap to detect presymptomatic spread of the disease in the spinal cord and monitor treatments targeting protein homeostasis and limiting spread, toward enhancing patient care.}, } @article {pmid37910250, year = {2024}, author = {Khamaysa, M and Lefort, M and Pélégrini-Issac, M and Lackmy-Vallée, A and Mendili, MME and Preuilh, A and Devos, D and Bruneteau, G and Salachas, F and Lenglet, T and Amador, MM and Le Forestier, N and Hesters, A and Gonzalez, J and Rolland, AS and Desnuelle, C and Chupin, M and Querin, G and Georges, M and Morelot-Panzini, C and Marchand-Pauvert, V and Pradat, PF and , }, title = {Quantitative brainstem and spinal MRI in amyotrophic lateral sclerosis: implications for predicting noninvasive ventilation needs.}, journal = {Journal of neurology}, volume = {271}, number = {3}, pages = {1235-1246}, pmid = {37910250}, issn = {1432-1459}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnostic imaging/therapy/complications ; *Noninvasive Ventilation/methods ; Disease Progression ; Magnetic Resonance Imaging/methods ; Brain Stem/diagnostic imaging ; }, abstract = {BACKGROUND: Respiratory complications resulting from motor neurons degeneration are the primary cause of death in amyotrophic lateral sclerosis (ALS). Predicting the need for non-invasive ventilation (NIV) in ALS is important for advance care planning and clinical trial design. The aim of this study was to assess the potential of quantitative MRI at the brainstem and spinal cord levels to predict the need for NIV during the first six months after diagnosis.

METHODS: Forty-one ALS patients underwent MRI and spirometry shortly after diagnosis. The need for NIV was monitored according to French health guidelines for 6 months. The performance of four regression models based on: clinical variables, brainstem structures volumes, cervical spinal measurements, and combined variables were compared to predict the need for NIV within this period.

RESULTS: Both the clinical model (R[2] = 0.28, AUC = 0.85, AICc = 42.67, BIC = 49.8) and the brainstem structures' volumes model (R[2] = 0.30, AUC = 0.85, AICc = 40.13, BIC = 46.99) demonstrated good predictive performance. In addition, cervical spinal cord measurements model similar performance (R[2] = 0.338, AUC = 0.87, AICc = 37.99, BIC = 44.49). Notably, the combined model incorporating predictors from all three models yielded the best performance (R[2] = 0.60, AUC = 0.959, AICc = 36.38, BIC = 44.8). These findings are supported by observed positive correlations between brainstem volumes, cervical (C4/C7) cross-sectional area, and spirometry-measured lung volumes.

CONCLUSIONS: Our study shows that brainstem volumes and spinal cord area are promising measures to predict respiratory intervention needs in ALS.}, } @article {pmid37909610, year = {2023}, author = {Reis, AHO and Figalo, LB and Orsini, M and Lemos, B}, title = {The implications of DNA methylation for amyotrophic lateral sclerosis.}, journal = {Anais da Academia Brasileira de Ciencias}, volume = {95}, number = {suppl 2}, pages = {e20230277}, doi = {10.1590/0001-3765202320230277}, pmid = {37909610}, issn = {1678-2690}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/metabolism ; DNA Methylation/genetics ; Mutation/genetics ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a complex and serious neurodegenerative disorder that develops in consequence of the progressive loss of the upper and lower motor neurons. Cases of ALS are classified as sporadic (sALS), or familial (fALS). Over 90% of cases are sALS, while roughly 10% are related to inherited genetic mutations (fALS). Approximately 70% of the genetic mutations that contribute to fALS have been identified. On the other hand, the majority of the sALS cases have an undetermined genetic contributor and few mutations have been described, despite the advanced genetic analysis methods. Also, several factors contribute to the onset and progression of ALS. Numerous lines of evidence indicate that epigenetic changes are linked to aging, as well as neurodegenerative disorders, such as ALS. In most cases, they act as the heritable regulation of transcription by DNA methylation, histone modification and expression of noncoding RNAs. Mechanisms involving aberrant DNA methylation could be relevant to human ALS pathobiology and therapeutic targeting. Despite advances in research to find factors associated with ALS and more effective treatments, this disease remains complex and has low patient survival. Here, we provide a narrative review of the role of DNA methylation for this complex neurodegenerative disorder.}, } @article {pmid37909302, year = {2024}, author = {Chen, S and Carter, D and Brockenbrough, PB and Cox, S and Gwathmey, K}, title = {Racial disparities in ALS diagnostic delay: a single center's experience and review of potential contributing factors.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {25}, number = {1-2}, pages = {112-118}, doi = {10.1080/21678421.2023.2273361}, pmid = {37909302}, issn = {2167-9223}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis ; Delayed Diagnosis ; Retrospective Studies ; Vital Capacity ; }, abstract = {OBJECTIVE: Outcomes for amyotrophic lateral sclerosis (ALS) patients are improved with prompt diagnosis, earlier initiation of disease-modifying treatments, and participation in a multidisciplinary clinic. We studied diagnostic delay and disease severity at time of clinic presentation between Black and non-Hispanic Caucasian ALS patients.

METHODS: We performed a retrospective analysis of non-Hispanic Caucasian and Black ALS patients seen in the Virginia Commonwealth University Health System multidisciplinary ALS clinic between 2017 and 2023. Diagnostic delay, ALS Functional Rating Scale-Revised (ALSFRS-R) and upright forced vital capacity (FVC) scores at baseline appointment were collected. Patient's distance from clinic and affluency of residential neighborhood were evaluated.

RESULTS: We analyzed 172 non-Hispanic Caucasian and 33 Black ALS patients. Black patients had a 64% increase in diagnostic delay compared to non-Hispanic Caucasian patients. Black patients had a lower performance on ALSFRS-R (5.3 points, p < 0.001) and FVC (17.9 percentage points p < 0.001) at time of first clinic visit. Black patients lived closer to clinic, with higher proportion living in the city of Richmond, but in less affluent areas with lower median house income ($55,300 ± 22,600 vs $69,900 ± 23,700).

DISCUSSION: Our findings demonstrate a large racial difference in ALS diagnostic delay, and greater disease severity and lower respiratory function at time of diagnosis for Black ALS patients. Delay in diagnosis prolongs access to disease-modifying therapies, multidisciplinary care, durable medical equipment, and respiratory and nutritional support. Potential sources of these racial disparities include providers' implicit bias and structural racism.}, } @article {pmid37908143, year = {2024}, author = {Azad, A and Gökmen, ÜR and Uysal, H and Köksoy, S and Bilge, U and Manguoğlu, AE}, title = {Autophagy dysregulation plays a crucial role in regulatory T-cell loss and neuroinflammation in amyotrophic lateral sclerosis (ALS).}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {25}, number = {3-4}, pages = {336-344}, doi = {10.1080/21678421.2023.2273365}, pmid = {37908143}, issn = {2167-9223}, mesh = {Humans ; *T-Lymphocytes, Regulatory/metabolism ; *Amyotrophic Lateral Sclerosis/metabolism ; Neuroinflammatory Diseases ; Autophagy ; Forkhead Transcription Factors/metabolism ; }, abstract = {OBJECTIVE: Neuroinflammation is the hallmark of amyotrophic lateral sclerosis (ALS) disease. Regulatory T cells (Tregs) are essential in immune tolerance and neuroinflammation prevention. It has been shown that a significant decrease in Treg and FoxP3 protein expression is observed in ALS patients. The main reason for the FoxP3[+] Treg loss in ALS is unknown. In this study, the role of autophagy dysregulation in FoxP3[+] Tregs in ALS was investigated.

METHODS: Twenty-three ALS patients and 24 healthy controls were recruited for the study. Mononuclear cells (MNCs) were obtained from peripheral blood, and then Tregs were isolated. Isolated Tregs were stained with FoxP3 and LC3 antibodies and analyzed in flow cytometry to determine autophagy levels in FoxP3[+] Tregs in patients and controls.

RESULTS: The mean of FoxP3[+] LC3[+] cells, were 0.47 and 0.45 in patients and controls, respectively. The mean of FoxP3[+] LC3- cells was 0.15 in patients and 0.20 in controls, p = 0.030 (p < 0.05). There is no significant correlation between ALSFRS-R decay rate and autophagy level in patients. Also, there is no significant difference between autophagy levels in FoxP3[+] Tregs in patients with rapidly progressing ALS and slow-progressing ALS.

CONCLUSION: Excessive autophagy levels in FoxP3[+] Tregs in ALS patients can potentially be an explanation for an increased cell death and result in worsened neuroinflammation and disease onset. However, the disease progress is not attributable to autophagy levels in FoxP3[+] Tregs.}, } @article {pmid37907717, year = {2024}, author = {Yamamoto, K and Itoi, T and Matsunami, Y and Sofuni, A and Tsuchiya, T and Mukai, S and Kojima, H and Minami, H and Nakatsubo, R and Tonozuka, R}, title = {Early and late effects of endoscopic interventions in patients with malignant afferent loop syndrome: A single-center experience and literature review.}, journal = {Journal of hepato-biliary-pancreatic sciences}, volume = {31}, number = {2}, pages = {120-132}, doi = {10.1002/jhbp.1380}, pmid = {37907717}, issn = {1868-6982}, mesh = {Humans ; *Afferent Loop Syndrome/diagnostic imaging/etiology/surgery ; *Cholestasis/etiology ; Drainage ; Endoscopy ; Endosonography ; Liver/pathology ; Retrospective Studies ; Stents/adverse effects ; Treatment Outcome ; }, abstract = {BACKGROUND/PURPOSE: Afferent loop syndrome (ALS) is a rare adverse event after gastrointestinal surgery requiring appropriate early decompression treatment. Several endoscopic interventions have been attempted for treatment, including endoscopic enteral metal stent placement (EMSP), endoscopic ultrasound (EUS)-guided entero-enterostomy (EUS-EE), and EUS-guided hepaticogastrostomy (EUS-HGS). However, there are limited data on outcomes, including duration of stent patency. In this study, we evaluated the usefulness of each endoscopic intervention for malignant ALS.

METHODS: We retrospectively investigated nine patients with malignant ALS who underwent EMSP, EUS-EE, or EUS-HGS. Information on technical success, clinical efficacy, adverse events, stent dysfunction, and overall survival was collected and analyzed.

RESULTS: The most common symptoms were abdominal pain and cholangitis. ALS was treated by EMSP in three patients, EUS-EE in three patients, and EUS-HGS in three patients. Stent placement was successful and clinically effective in all patients with no adverse events. During follow-up, stent dysfunction occurred in two patients treated by EUS-HGS. Eight patients died of primary disease during a median follow-up of 157 days.

CONCLUSIONS: Each of the available endoscopic interventions for malignant ALS can be expected to produce similar outcomes, including duration of stent patency. The choice of endoscopic intervention should be made based on the characteristics of each treatment.}, } @article {pmid37907134, year = {2023}, author = {Birajdar, SV and Mazahir, F and Alam, MI and Kumar, A and Yadav, AK}, title = {Repurposing and clinical attributes of antidiabetic drugs for the treatment of neurodegenerative disorders.}, journal = {European journal of pharmacology}, volume = {961}, number = {}, pages = {176117}, doi = {10.1016/j.ejphar.2023.176117}, pmid = {37907134}, issn = {1879-0712}, mesh = {Humans ; Mice ; Animals ; Hypoglycemic Agents/pharmacology/therapeutic use ; Amyloid beta-Peptides/metabolism ; *Diabetes Mellitus, Type 2/drug therapy ; Drug Repositioning ; Neuroinflammatory Diseases ; *Alzheimer Disease/drug therapy ; Insulin/metabolism ; *Metformin/pharmacology ; }, abstract = {The risk of neurodegeneration was found to be increased among people with type 2 diabetes mellitus (T2DM). Brain disorders like Alzheimer's disease, Parkinson's disease, Huntington's disease, Amyotrophic lateral sclerosis, and others are considered neurodegenerative diseases and can be characterized by progressive loss of neurons. The deficiency of insulin, impaired signaling, and its resistance lead to alteration in the neuronal functioning of the brain. Insulin degrading enzyme (IDE) plays a significant role in the amyloid β metabolism, aggregation, and deposition of misfolded proteins in the brain's hippocampal and cortical neuronal regions. The insulin signaling via IP3 activation upregulates the IDE and could be a promising approach to regulate neurodegeneration. The repurposing of existing antidiabetic drugs such as Metformin, DPP-4 inhibitors, thiazolidinediones, glucagon-like peptides (GLP-1), sodium-glucose co-transport-2 (SGCT-2) inhibitors, and insulin could be an alternative and effective strategy to treat neurodegeneration via modulating insulin signaling, insulin resistance, IDE activity, oxidative stress, mitochondrial dysfunction, serum lipid profile and neuroinflammation in the brain. Antidiabetic medications reduce the risk of neuroinflammation, oxidative stress, and Aβ deposition by enhancing their clearance rate. The downregulation of IDE alters the degradation of Aβ monomers in the Tg2576 APP mice. Also, the treatment with metformin activated the AMPK pathway and suppressed mTOR and BACE-1 protein expression in the APP/PS1-induced mice model. Thus, the primary intention of this review is to explore the link between T2DM and neurodegenerative disorders, and the possible role of various antidiabetic drugs in the management of neurodegenerative disorders.}, } @article {pmid37906991, year = {2023}, author = {Prohaska, S and Matthias, K}, title = {Effectiveness of Mindfulness-Based Stress Reduction as a Nondrug Preventive Intervention in Patients with Migraine: A Systematic Review with Meta-Analyses.}, journal = {Complementary medicine research}, volume = {30}, number = {6}, pages = {525-534}, doi = {10.1159/000534653}, pmid = {37906991}, issn = {2504-2106}, mesh = {Adult ; Humans ; *Mindfulness ; Treatment Outcome ; *Migraine Disorders/prevention & control ; Headache ; Stress, Psychological ; }, abstract = {INTRODUCTION: Migraine is a neurological disorder characterized by recurrent, severe headaches that are often accompanied by other symptoms. There are various factors that can trigger a migraine in sufferers. Stress can be such a trigger. Drug and nondrug treatments are available for the preventive treatment of migraine. According to a German guideline, mindfulness can be recommended for the prophylaxis of migraine. Therefore, the aim was to investigate the effectiveness of mindfulness-based stress reduction (MBSR) in relation to patient-relevant outcomes in adult patients with migraine. Patient-relevant outcomes in this context are migraine frequency, headache intensity during a migraine attack, depressive symptoms, and quality of life.

MATERIAL AND METHODS: The conduct of this study was guided by the PRISMA 2020 statement. A systematic literature search for randomized controlled trials (RCTs) of the effectiveness of MBSR in adult migraine patients was conducted in December 2021 in three databases: MEDLINE via PubMed, the Cochrane Library, and Web of Science. In addition, a review of reference lists and a search of study registries were performed. The last search was conducted on October 7, 2022. In a two-step process, studies were selected based on predefined inclusion and exclusion criteria. The potential for bias was assessed using the Cochrane Risk of Bias Tool 2. The results were summarized descriptively and by means of quantitative synthesis.

RESULTS: Four RCTs with a total of 275 patients and the follow-up publication of one of these studies were included. The risk of bias in one study each was judged to be low or of some concern and high in two studies. Four studies were included in the quantitative analysis. For the endpoint migraine frequency, the meta-analytic summary of three studies failed to show a statistically significant benefit for MBSR (SMD: -0.23; 95% CI: -0.79 to 0.32). For the endpoint depressive symptoms, a meta-analytic summary of three studies showed a statistically significant benefit for MBSR (SMD: -0.59; 95% CI: -0.93 to -0.25). No study had examined the severity of headaches during a migraine episode.

CONCLUSION: Some results suggest that migraine patients may benefit from MBSR. However, the evidence base is currently insufficient for recommendations on the use of MBSR as a nondrug treatment option. Further adequately powered, high-quality RCTs are needed.

UNLABELLED: EinleitungMigräne ist eine neurologische Erkrankung, die durch wiederkehrende, starke Kopfschmerzen gekennzeichnet ist, die häufig von anderen Symptomen einhergehen. Es gibt verschiedene Faktoren, die bei den Betroffenen eine Migräne auslösen können. Ein solcher Auslöser kann Stress sein. Für die präventive Behandlung der Migräne stehen medikamentöse und nichtmedikamentöse Verfahren zur Verfügung. Laut einer deutschen Leitlinie kann Achtsamkeit zur Prophylaxe von Migräne empfohlen werden. Ziel der Studie war es daher, die Wirksamkeit von achtsamkeitsbasierter Stressreduktion (MBSR) in Bezug auf patientenrelevante Outcomes bei erwachsenen Migränepatienten zu untersuchen. Patientenrelevante Outcomes in diesem Zusammenhang sind Migränehäufigkeit, Kopfschmerzintensität während einer Migräneattacke, depressive Symptome und Lebensqualität.MethodenDie Durchführung dieser Studie orientierte sich am PRISMA-Statement. Eine systematische Literatursuche nach randomisierten kontrollierten Studien zur Wirksamkeit von MBSR bei erwachsenen Migränepatienten wurde im Dezember 2021 in drei Datenbanken durchgeführt: MEDLINE über PubMed, die Cochrane Library und Web of Science. Darüber hinaus wurden Referenzlisten und Studienregister durchsucht. Die letzte Suche erfolgte am 7. Oktober 2022. In einem zweistufigen Verfahren wurden die Studien anhand von vordefinierten Ein- und Ausschlusskriterien ausgewählt. Das Verzerrungspotential der Studien wurde mit dem Cochrane Risk of Bias Tool 2 bewertet. Die Ergebnisse wurden deskriptiv und mit Hilfe einer quantitativen Synthese zusammengefasst.ErgebnisseEs wurden vier randomisiert-kontrollierte Studien mit insgesamt 275 Patienten und die Nachfolgepublikation einer dieser Studien eingeschlossen. Das Verzerrungspotential wurde bei je einer Studie als gering oder bedenklich und bei zwei Studien als hoch eingestuft. Vier Studien wurden in die quantitative Analyse einbezogen. Für den Endpunkt Migränehäufigkeit ergab die metaanalytische Zusammenfassung von drei Studien keinen statistisch signifikanten Vorteil für MBSR (SMD −0.23; 95% CI −0.79 bis 0.32). Für den Endpunkt depressive Symptome zeigte eine metaanalytische Zusammenfassung von drei Studien einen statistisch signifikanten Vorteil für MBSR (SMD −0.59; 95% CI −0.93 bis −0.25). Keine Studie hatte die Schwere der Kopfschmerzen während einer Migräneepisode untersucht.SchlussfolgerungEinige Ergebnisse deuten darauf hin, dass Migränepatienten von MBSR profitieren können. Allerdings ist die Evidenzbasis derzeit nicht ausreichend, um Empfehlungen für den Einsatz von MBSR als nichtmedikamentöse Behandlungsoption abzuleiten. Es werden daher weitere qualitativ hochwertige randomisiert-kontrollierte Studien mit ausreichender statistischer Power benötigt.}, } @article {pmid37906785, year = {2022}, author = {Matamala, JM and Moreno-Roco, J and Acosta, I and Hughes, R and Lillo, P and Casar, JC and Earle, N}, title = {[Multidisciplinary care and therapeutic advances in amyotrophic lateral sclerosis].}, journal = {Revista medica de Chile}, volume = {150}, number = {12}, pages = {1633-1646}, doi = {10.4067/s0034-98872022001201633}, pmid = {37906785}, issn = {0717-6163}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy/diagnosis/psychology ; *Neurodegenerative Diseases ; Quality of Life ; Palliative Care ; Disease Progression ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that mainly affects the motor system, resulting in progressive weakness and muscle wasting. Despite the tremendous advances in physiopathological and clinical characterization, we do not have a curative treatment yet. The progressive and fatal course of ALS makes its management particularly complex and challenging given the diversity of symptoms presenting during the disease progression. The main goal in the treatment of ALS patients is to minimize morbidity and maximize the quality of life. Currently, a series of therapeutic interventions improve the quality of life and prolong survival, including multidisciplinary care, respiratory management, and disease-modifying therapy. Within the supportive interventions, weight maintenance through nutritional and metabolic support is critical. In addition, the management of neuropsychiatric manifestations and preservation of communicative capacity before speech loss are also crucial. Lastly, early palliative care intervention is essential to optimize symptomatic management. Anticipatory guidelines to face the inevitable patient deterioration should be devised. This article updates the main therapeutic strategies used in these patients, including evolving clinical trials with promising novel therapies.}, } @article {pmid37906538, year = {2023}, author = {Dong, H and Zhang, H and Jalin, J and He, Z and Wang, R and Huang, L and Liu, Z and Zhang, S and Dai, B and Li, D}, title = {Nucleocapsid proteins from human coronaviruses possess phase separation capabilities and promote FUS pathological aggregation.}, journal = {Protein science : a publication of the Protein Society}, volume = {32}, number = {12}, pages = {e4826}, pmid = {37906538}, issn = {1469-896X}, support = {32170683//National Natural Science Foundation of China/ ; }, mesh = {Humans ; *Nucleocapsid Proteins/genetics/metabolism ; Amyloid/metabolism ; Amyloidogenic Proteins/metabolism ; *Amyotrophic Lateral Sclerosis/metabolism ; SARS-CoV-2/genetics/metabolism ; RNA-Binding Protein FUS/chemistry ; }, abstract = {The nucleocapsid (N) protein is an essential structural component necessary for genomic packaging and replication in various human coronaviruses (HCoVs), such as SARS-CoV-2 and MERS-CoV. Recent studies have revealed that the SARS-CoV-2 N protein exhibits a high capacity for liquid-liquid phase separation (LLPS), which plays multiple roles in viral infection and replication. In this study, we systematically investigate the LLPS capabilities of seven homologous N proteins from different HCoVs using a high-throughput protein phase separation assay. We found that LLPS is a shared intrinsic property among these N proteins. However, the phase separation profiles of the various N protein homologs differ, and they undergo phase separation under distinct in vitro conditions. Moreover, we demonstrate that N protein homologs can co-phase separate with FUS, a SG-containing protein, and accelerate its liquid-to-solid phase transition and amyloid aggregation, which is closely related to amyotrophic lateral sclerosis. Further study shows that N protein homologs can directly bind to the low complexity domain of FUS. Together, our work demonstrates that N proteins of different HCoVs possess phase separation capabilities, which may contribute to promoting pathological aggregation of host proteins and disrupting SG homeostasis during the infection and replication of various HCoVs.}, } @article {pmid37905874, year = {2024}, author = {Abyadeh, M and Gupta, V and Paulo, JA and Mahmoudabad, AG and Shadfar, S and Mirshahvaladi, S and Gupta, V and Nguyen, CTO and Finkelstein, DI and You, Y and Haynes, PA and Salekdeh, GH and Graham, SL and Mirzaei, M}, title = {Amyloid-beta and tau protein beyond Alzheimer's disease.}, journal = {Neural regeneration research}, volume = {19}, number = {6}, pages = {1262-1276}, pmid = {37905874}, issn = {1673-5374}, support = {R01 GM132129/GM/NIGMS NIH HHS/United States ; }, abstract = {The aggregation of amyloid-beta peptide and tau protein dysregulation are implicated to play key roles in Alzheimer's disease pathogenesis and are considered the main pathological hallmarks of this devastating disease. Physiologically, these two proteins are produced and expressed within the normal human body. However, under pathological conditions, abnormal expression, post-translational modifications, conformational changes, and truncation can make these proteins prone to aggregation, triggering specific disease-related cascades. Recent studies have indicated associations between aberrant behavior of amyloid-beta and tau proteins and various neurological diseases, such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis, as well as retinal neurodegenerative diseases like Glaucoma and age-related macular degeneration. Additionally, these proteins have been linked to cardiovascular disease, cancer, traumatic brain injury, and diabetes, which are all leading causes of morbidity and mortality. In this comprehensive review, we provide an overview of the connections between amyloid-beta and tau proteins and a spectrum of disorders.}, } @article {pmid37905867, year = {2024}, author = {Xiong, W and Lu, L and Li, J}, title = {Long non-coding RNAs with essential roles in neurodegenerative disorders.}, journal = {Neural regeneration research}, volume = {19}, number = {6}, pages = {1212-1220}, pmid = {37905867}, issn = {1673-5374}, abstract = {Recently, with the advent of high-resolution and high-throughput sequencing technologies, an increasing number of long non-coding RNAs (lncRNAs) have been found to be involved in the regulation of neuronal function in the central nervous system with specific spatiotemporal patterns, across different neurodegenerative diseases. However, the underlying mechanisms of lncRNAs during neurodegeneration remain poorly understood. This review provides an overview of the current knowledge of the biology of lncRNAs and focuses on introducing the latest identified roles, regulatory mechanisms, and research status of lncRNAs in Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. Finally, this review discusses the potential values of lncRNAs as diagnostic biomarkers and therapeutic targets for neurodegenerative diseases, hoping to provide broader implications for developing effective treatments.}, } @article {pmid37905864, year = {2024}, author = {Cauchi, RJ}, title = {SCFD1 in amyotrophic lateral sclerosis: reconciling a genetic association with in vivo functional analysis.}, journal = {Neural regeneration research}, volume = {19}, number = {6}, pages = {1201-1202}, pmid = {37905864}, issn = {1673-5374}, } @article {pmid37905855, year = {2024}, author = {Claud, K and Sun, J}, title = {Metabolites and micronutrition in modulating amyotrophic lateral sclerosis.}, journal = {Neural regeneration research}, volume = {19}, number = {6}, pages = {1183-1184}, pmid = {37905855}, issn = {1673-5374}, } @article {pmid37904275, year = {2024}, author = {Kacem, I and Sghaier, I and Peverelli, S and Abida, Y and Ben Brahim, H and Ratti, A and Nasri, A and Ticozzi, N and Silani, V and Gouider, R}, title = {Optineurin in patients with Amyotrophic Lateral Sclerosis associated to atypical Parkinsonism in Tunisian population.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {25}, number = {1-2}, pages = {128-134}, doi = {10.1080/21678421.2023.2273961}, pmid = {37904275}, issn = {2167-9223}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics ; Family ; *Frontotemporal Dementia/genetics ; Mutation/genetics ; *Parkinson Disease ; }, abstract = {Amyotrophic Lateral Sclerosis (ALS) is a heterogeneous disorder and the phenotypic variability goes far beyond the used clinical stratification parameter. Evidence has emerged that ALS may coexist with distinct neurodegenerative diseases in single cases. We aim to study the clinical features of two familial cases of ALS carriers of two distinct variants harbored in the Optineurin (OPTN) gene. We included definite familial ALS followed up in the Department of Neurology of Razi University Hospital, Tunisia, and selected according to Byrne criteria. Preliminary screening for the four main ALS genes (SOD1, C9ORF72, TARDBP, FUS) was conducted. Given the negative results, we proceeded to NGS target-re-sequencing with a custom panel including genes associated with ALS-FTD, Alzheimer's, and Parkinson's diseases. Both families are carriers of two different OPTN variants and they present very different ALS clinical features. The first family comprises two siblings diagnosed with ALS and Corticobasal syndrome (ALS-CBS) at an early age of onset and carriers of OPTN p.E135X in the homozygous state. The proband for the second family was diagnosed with ALS at an early age of onset presenting as progressive muscular atrophy with rapid progression. Genetic analysis revealed the presence of the homozygous variant p.R520H. Our findings highlight the peculiarity of genetic Tunisian drift. Indeed, genes with a recessive mode of inheritance may explain part of ALS diversity in clinical features. Therefore, the screening of the OPTN gene is highly recommended among inbreeding populations such as the Tunisian one.}, } @article {pmid37904013, year = {2024}, author = {Chen, X and Luo, J and Zheng, W and Huang, Q and Du, C and Yuan, H and Xiao, F}, title = {Hyperhidrosis as the initial symptom in FUS mutation-associated amyotrophic lateral sclerosis: a case report and comprehensive literature review.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {45}, number = {4}, pages = {1523-1527}, pmid = {37904013}, issn = {1590-3478}, mesh = {Female ; Humans ; Young Adult ; *Amyotrophic Lateral Sclerosis/complications/diagnosis/genetics ; *Hyperhidrosis/genetics ; Mutation ; *Neurodegenerative Diseases ; Quality of Life ; RNA-Binding Protein FUS/genetics ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that is now recognized to involve autonomic dysfunction. The burden of autonomic dysfunction is an important factor in the quality of life and prognosis of ALS patients. This article presents the clinical characteristics of a young female ALS patient with a fused in sarcoma (FUS) gene mutation and notable hyperhidrosis.

METHOD: Detailed clinical characteristics of the patients were collected, and comprehensive examinations such as electrophysiological assessment, neuro-ultrasound, genetic testing, and relevant blood tests were conducted.

RESULT: A 24-year-old female experienced progressive weakness in both lower limbs for over 5 months, along with excessive sweating on both palms and feet. A positive skin iodine-starch test was observed. Electromyography revealed extensive neurogenic damage and prolonged sympathetic skin response (SSR) latency in both lower limbs. Full exon gene sequencing showed a heterozygous mutation c.1574C>T (p.Pro525Leu) in the FUS gene.

CONCLUSION: The pathogenesis of ALS remains unclear at present. This case underscores the presence of autonomic nervous symptoms in ALS associated with FUS mutation and highlights the importance of early diagnosis and timely treatment intervention to enhance patient prognosis.}, } @article {pmid37902807, year = {2024}, author = {Sampson, CS and Maberry, MD and Stilley, JA}, title = {Football Saturday: are collegiate football stadiums adequately prepared to handle spectator emergencies?.}, journal = {The Journal of sports medicine and physical fitness}, volume = {64}, number = {1}, pages = {73-77}, doi = {10.23736/S0022-4707.23.15428-4}, pmid = {37902807}, issn = {1827-1928}, mesh = {Humans ; Emergencies ; *Emergency Medical Services/organization & administration ; *Football ; *Sports and Recreational Facilities/organization & administration ; }, abstract = {BACKGROUND: Mass gatherings are a commonly occurring event, especially on college campuses. Any mass gathering gives rise to possible small- or large-scale emergencies. Mass gathering medicine is an integral part of emergency medical services (EMS). An assessment was performed to see if collegiate stadiums possess capabilities for advanced medical care when emergencies arise among attendees.

METHODS: A standardized survey was sent by a single researcher to all National Collegiate Athletic Association (NCAA) Division I programs regarding medical services they currently have in place at their stadiums during Saturday football games. A follow-up inquiry was made at each local community office of emergency management (OEM) to confirm responses or obtain missing data.

RESULTS: Only 21.5% (N.=17) of stadium facilities reported having physicians solely dedicated to the care of fans and other support staff. Most stadiums (N.=70, 88.6%) offered ALS services for their fans, with the remaining ALS services provided by paramedics (N.=46, 58.2%) or registered nurses (N.=7, 8.9%). The remaining stadiums only offered BLS services (N.=6, 7.6%) or basic first aid (N.=3, 3.8%). One stadium offered athletic trainer services to its fan in addition to the ALS care.

CONCLUSIONS: Given the potential for a large influx of patients at sporting events, almost all stadiums have some degree of prehospital emergency care on site. More than a 10% of stadiums lacked ALS services and very few stadiums have physicians on site. Many stadiums were unaware of the resources available during these events. The ability to have ALS services on site who can provide rapid, advanced care to spectators is important due to likely delays in 911 response. At a minimum ALS services should be available within the stadium with consideration of physician coverage as well.}, } @article {pmid37901127, year = {2023}, author = {Aslam, A and Sarmad, E and Nawaz, A and Numan, A and Ahmad, A and Hassan, MA}, title = {Brait-Fahn-Schwartz Disease: A Unique Co-Occurrence of Parkinson's Disease and Amyotrophic Lateral Sclerosis.}, journal = {Case reports in neurology}, volume = {15}, number = {1}, pages = {207-214}, pmid = {37901127}, issn = {1662-680X}, abstract = {The Parkinson's disease-amyotrophic lateral sclerosis (ALS) complex typically manifests as levodopa-responsive parkinsonism, followed by ALS. It is extremely rare for Parkinson's disease and ALS to coexist without other neurological disorders. Named after the scientists who first described this overlap of two neurodegenerative conditions, it is referred to as Brait-Fahn-Schwartz disease. Given its variable presentation, increasing rarity, and lack of any diagnostic test, it poses a diagnostic challenge for physicians. We present a case of a 55-year-old Pakistani male experiencing progressive quadriparesis with spastic lower limbs and flaccid upper limbs, in addition to the cardinal features of idiopathic Parkinson's disease. Since there is currently no cure available for either Parkinson's disease or ALS, all available treatment focuses on improving quality of life, which we achieved in our patient. This case is unique in being the first incidence of Parkinson's disease-ALS complex in a novel geographic region such as Pakistan, where genetic testing and cost constraints limit the diagnosis of rare disorders. The coexistence of extrapyramidal symptoms and pyramidal symptoms is uncommon. In such situations, physicians may overlook one group of symptoms, potentially leading to a misdiagnosis. This case highlights the value of a thorough physical examination and electrodiagnostic studies and suggests the association between Parkinson's disease and ALS. This case demonstrates the significance of understanding when Parkinson's disease symptoms start to appear in patients with ALS and the need to start dopaminergic therapy in those who had Parkinson's disease features before ALS to alleviate the suffering of an individual and enhance quality of life.}, } @article {pmid37898010, year = {2023}, author = {Halkiadakis, Y and Davidson, N and Morgan, KD}, title = {Time series modeling characterizes stride time variability to identify individuals with neurodegenerative disorders.}, journal = {Human movement science}, volume = {92}, number = {}, pages = {103152}, doi = {10.1016/j.humov.2023.103152}, pmid = {37898010}, issn = {1872-7646}, mesh = {Humans ; Time Factors ; *Amyotrophic Lateral Sclerosis ; *Neurodegenerative Diseases/diagnosis ; Gait/physiology ; Walking/physiology ; *Huntington Disease ; }, abstract = {The progressive death and dysfunction of neurons causes altered stride-to-stride variability in individuals with Amyotrophic Lateral Sclerosis (ALS) and Huntington's Disease (HD). Yet these altered gait dynamics can manifest differently in these populations based on how and where these neurodegenerative disorders attack the central nervous system. Time series analyses can quantify differences in stride time variability which can help contribute to the detection and identification of these disorders. Here, autoregressive modeling time series analysis was utilized to quantify differences in stride time variability amongst the Controls, the individuals with ALS, and the individuals with HD. For this study, fifteen Controls, 12 individuals with ALS and 15 individuals with HD walked up and down a hallway continuously for 5-min. Participants wore force sensitive resistors in their shoes to collect stride time data. A second order autoregressive (AR) model was fit to the time series created from the stride time data. The mean stride time and two AR model coefficients served as metrics to identify differences in stride time variability amongst the three groups. The individuals with HD walked with significantly greater stride time variability indicating a more chaotic gait while the individuals with ALS adopted more ordered, less variable stride time dynamics (p < 0.001). A plot of the stride time metrics illustrated how each group exhibited significantly different stride time dynamics. The stride time metrics successfully quantified differences in stride time variability amongst individuals with neurodegenerative disorders. This work provided valuable insight about how these neuromuscular disorders disrupt motor coordination leading to the adoption of new gait dynamics.}, } @article {pmid37897436, year = {2024}, author = {Connolly, A and Bailey, S and Lamont, R and Tu, A}, title = {Factors associated with assistive technology prescription and acceptance in motor neurone disease.}, journal = {Disability and rehabilitation. Assistive technology}, volume = {19}, number = {6}, pages = {2229-2238}, doi = {10.1080/17483107.2023.2272858}, pmid = {37897436}, issn = {1748-3115}, mesh = {Humans ; *Motor Neuron Disease/rehabilitation ; *Self-Help Devices ; Male ; Female ; Middle Aged ; *Focus Groups ; *Qualitative Research ; Adult ; Quality of Life ; Aged ; Attitude of Health Personnel ; Interviews as Topic ; Patient Acceptance of Health Care ; }, abstract = {PURPOSE: The risk of delaying assistive technology (AT) prescription and implementation has significant implications on the safety and quality of life of people with Motor Neurone Disease (PwMND). This study aims to explore the barriers and enablers of AT prescription and implementation identified by PwMND and clinicians.

METHODS: A qualitative study using semi-structured focus groups with clinicians and in-depth interviews with PwMND. Sixteen clinicians and ten PwMND were recruited. Thematic analysis was completed and results were compared and discussed to reach an agreement on the final themes.

RESULTS: Three main factors were identified - PwMND, Clinician and Extrapersonal. For PwMND, personal characteristics, such as mindset, was the strongest enabler and inability to accept diagnosis and AT was the key barrier. For Clinician, communication approach was both the most identified enabler and barrier. For Extrapersonal, the availability of interactive education of AT was the strongest enabler and long wait time was a significant barrier.

CONCLUSION: Our study identified themes that clinicians could have an impact on, such as, providing interactive education, engaging PwMND and their support network, and ongoing upskilling of clinicians working in this field. Themes identified that were beyond the control of clinicians were personal characteristics, acceptance and support networks. It highlights the importance for clinicians to be flexible with their communication approach to accommodate the needs of PwMND in the acceptance of AT.}, } @article {pmid37895110, year = {2023}, author = {Provenzano, F and Torazza, C and Bonifacino, T and Bonanno, G and Milanese, M}, title = {The Key Role of Astrocytes in Amyotrophic Lateral Sclerosis and Their Commitment to Glutamate Excitotoxicity.}, journal = {International journal of molecular sciences}, volume = {24}, number = {20}, pages = {}, pmid = {37895110}, issn = {1422-0067}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism ; Glutamic Acid/metabolism ; Astrocytes/metabolism ; Neuroglia/metabolism ; Neurons/metabolism ; }, abstract = {In the last two decades, there has been increasing evidence supporting non-neuronal cells as active contributors to neurodegenerative disorders. Among glial cells, astrocytes play a pivotal role in driving amyotrophic lateral sclerosis (ALS) progression, leading the scientific community to focus on the "astrocytic signature" in ALS. Here, we summarized the main pathological mechanisms characterizing astrocyte contribution to MN damage and ALS progression, such as neuroinflammation, mitochondrial dysfunction, oxidative stress, energy metabolism impairment, miRNAs and extracellular vesicles contribution, autophagy dysfunction, protein misfolding, and altered neurotrophic factor release. Since glutamate excitotoxicity is one of the most relevant ALS features, we focused on the specific contribution of ALS astrocytes in this aspect, highlighting the known or potential molecular mechanisms by which astrocytes participate in increasing the extracellular glutamate level in ALS and, conversely, undergo the toxic effect of the excessive glutamate. In this scenario, astrocytes can behave as "producers" and "targets" of the high extracellular glutamate levels, going through changes that can affect themselves and, in turn, the neuronal and non-neuronal surrounding cells, thus actively impacting the ALS course. Moreover, this review aims to point out knowledge gaps that deserve further investigation.}, } @article {pmid37895020, year = {2023}, author = {Davis, SE and Cirincione, AB and Jimenez-Torres, AC and Zhu, J}, title = {The Impact of Neurotransmitters on the Neurobiology of Neurodegenerative Diseases.}, journal = {International journal of molecular sciences}, volume = {24}, number = {20}, pages = {}, pmid = {37895020}, issn = {1422-0067}, support = {R01 DA057866/DA/NIDA NIH HHS/United States ; F31 DA057163/DA/NIDA NIH HHS/United States ; R01 DA047924/DA/NIDA NIH HHS/United States ; R01 DA035714/DA/NIDA NIH HHS/United States ; DA047924/NH/NIH HHS/United States ; DA035714/NH/NIH HHS/United States ; DA057866/NH/NIH HHS/United States ; DA057163/NH/NIH HHS/United States ; }, mesh = {Humans ; *Neurodegenerative Diseases/pathology ; *Alzheimer Disease/pathology ; Brain/pathology ; *Huntington Disease/pathology ; *HIV Infections/pathology ; }, abstract = {Neurodegenerative diseases affect millions of people worldwide. Neurodegenerative diseases result from progressive damage to nerve cells in the brain or peripheral nervous system connections that are essential for cognition, coordination, strength, sensation, and mobility. Dysfunction of these brain and nerve functions is associated with Alzheimer's disease, Parkinson's disease, Huntington's disease, Amyotrophic lateral sclerosis, and motor neuron disease. In addition to these, 50% of people living with HIV develop a spectrum of cognitive, motor, and/or mood problems collectively referred to as HIV-Associated Neurocognitive Disorders (HAND) despite the widespread use of a combination of antiretroviral therapies. Neuroinflammation and neurotransmitter systems have a pathological correlation and play a critical role in developing neurodegenerative diseases. Each of these diseases has a unique pattern of dysregulation of the neurotransmitter system, which has been attributed to different forms of cell-specific neuronal loss. In this review, we will focus on a discussion of the regulation of dopaminergic and cholinergic systems, which are more commonly disturbed in neurodegenerative disorders. Additionally, we will provide evidence for the hypothesis that disturbances in neurotransmission contribute to the neuronal loss observed in neurodegenerative disorders. Further, we will highlight the critical role of dopamine as a mediator of neuronal injury and loss in the context of NeuroHIV. This review will highlight the need to further investigate neurotransmission systems for their role in the etiology of neurodegenerative disorders.}, } @article {pmid37894774, year = {2023}, author = {Moțățăianu, A and Șerban, G and Andone, S}, title = {The Role of Short-Chain Fatty Acids in Microbiota-Gut-Brain Cross-Talk with a Focus on Amyotrophic Lateral Sclerosis: A Systematic Review.}, journal = {International journal of molecular sciences}, volume = {24}, number = {20}, pages = {}, pmid = {37894774}, issn = {1422-0067}, support = {PN-III-P1-1.1-TE-2021-0960//Ministry of Research, Innovation and Digitization, CNCS - UEFISCDI/ ; }, mesh = {Humans ; Aged ; *Gastrointestinal Microbiome/physiology ; *Amyotrophic Lateral Sclerosis/metabolism ; *Neurodegenerative Diseases/metabolism ; Brain/metabolism ; Fatty Acids, Volatile/metabolism ; Fatty Acids/metabolism ; }, abstract = {Amyotrophic lateral sclerosis is a devastating neurodegenerative disease characterized by the gradual loss of motor neurons in the brain and spinal cord, leading to progressive motor function decline. Unfortunately, there is no effective treatment, and its increasing prevalence is linked to an aging population, improved diagnostics, heightened awareness, and changing lifestyles. In the gastrointestinal system, the gut microbiota plays a vital role in producing metabolites, neurotransmitters, and immune molecules. Short-chain fatty acids, of interest for their potential health benefits, are influenced by a fiber- and plant-based diet, promoting a diverse and balanced gut microbiome. These fatty acids impact the body by binding to receptors on enteroendocrine cells, influencing hormones like glucagon-like peptide-1 and peptide YY, which regulate appetite and insulin sensitivity. Furthermore, these fatty acids impact the blood-brain barrier, neurotransmitter levels, and neurotrophic factors, and directly stimulate vagal afferent nerves, affecting gut-brain communication. The vagus nerve is a crucial link between the gut and the brain, transmitting signals related to appetite, inflammation, and various processes. Dysregulation of this pathway can contribute to conditions like obesity and irritable bowel syndrome. Emerging evidence suggests the complex interplay among these fatty acids, the gut microbiota, and environmental factors influences neurodegenerative processes via interconnected pathways, including immune function, anti-inflammation, gut barrier, and energy metabolism. Embracing a balanced, fiber-rich diet may foster a diverse gut microbiome, potentially impacting neurodegenerative disease risk. Comprehensive understanding requires further research into interventions targeting the gut microbiome and fatty acid production and their potential therapeutic role in neurodegeneration.}, } @article {pmid37893463, year = {2023}, author = {Laucius, O and Drūteika, J and Balnytė, R and Petrikonis, K and Ališauskienė, M and Vaitkus, A}, title = {Sonographic Phrenic Nerve Changes in Amyotrophic Lateral Sclerosis.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {59}, number = {10}, pages = {}, pmid = {37893463}, issn = {1648-9144}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/complications/diagnostic imaging ; Phrenic Nerve/physiology ; *Neurodegenerative Diseases ; Prognosis ; Muscle Weakness/complications ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that affects both the upper and lower motor neurons in the nervous system, causing muscle weakness and severe disability. The progressive course of the disease reduces the functional capacity of the affected patients, limits daily activities, and leads to complete dependence on caregivers, ultimately resulting in a fatal outcome. Respiratory dysfunction mostly occurs later in the disease and is associated with a worse prognosis. Forty-six participants were included in our study, with 23 patients in the ALS group and 23 individuals in the control group. The ultrasound examination of the phrenic nerve (PN) was performed by two authors using a high-resolution "Philips EPIQ 7" ultrasound machine with a linear 4-18 MHz transducer. Our study revealed that the phrenic nerve is significantly smaller on both sides in ALS patients compared to the control group (p < 0.001). Only one significant study on PN ultrasound in ALS, conducted in Japan, also showed significant results (p < 0.00001). These small studies are particularly promising, as they suggest that ultrasound findings could serve as an additional diagnostic tool for ALS.}, } @article {pmid37893165, year = {2023}, author = {De Marchi, F and Munitic, I and Vidatic, L and Papić, E and Rački, V and Nimac, J and Jurak, I and Novotni, G and Rogelj, B and Vuletic, V and Liscic, RM and Cannon, JR and Buratti, E and Mazzini, L and Hecimovic, S}, title = {Overlapping Neuroimmune Mechanisms and Therapeutic Targets in Neurodegenerative Disorders.}, journal = {Biomedicines}, volume = {11}, number = {10}, pages = {}, pmid = {37893165}, issn = {2227-9059}, abstract = {Many potential immune therapeutic targets are similarly affected in adult-onset neurodegenerative diseases, such as Alzheimer's (AD) disease, Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and frontotemporal dementia (FTD), as well as in a seemingly distinct Niemann-Pick type C disease with primarily juvenile onset. This strongly argues for an overlap in pathogenic mechanisms. The commonly researched immune targets include various immune cell subsets, such as microglia, peripheral macrophages, and regulatory T cells (Tregs); the complement system; and other soluble factors. In this review, we compare these neurodegenerative diseases from a clinical point of view and highlight common pathways and mechanisms of protein aggregation, neurodegeneration, and/or neuroinflammation that could potentially lead to shared treatment strategies for overlapping immune dysfunctions in these diseases. These approaches include but are not limited to immunisation, complement cascade blockade, microbiome regulation, inhibition of signal transduction, Treg boosting, and stem cell transplantation.}, } @article {pmid37893003, year = {2023}, author = {Wu, YS and Taniar, D and Adhinugraha, K and Tsai, LK and Pai, TW}, title = {Detection of Amyotrophic Lateral Sclerosis (ALS) Comorbidity Trajectories Based on Principal Tree Model Analytics.}, journal = {Biomedicines}, volume = {11}, number = {10}, pages = {}, pmid = {37893003}, issn = {2227-9059}, support = {MOST 111-2221-E-027 -113 -MY2//National Science and Technology Council/ ; }, abstract = {The multifaceted nature and swift progression of Amyotrophic Lateral Sclerosis (ALS) pose considerable challenges to our understanding of its evolution and interplay with comorbid conditions. This study seeks to elucidate the temporal dynamics of ALS progression and its interaction with associated diseases. We employed a principal tree-based model to decipher patterns within clinical data derived from a population-based database in Taiwan. The disease progression was portrayed as branched trajectories, each path representing a series of distinct stages. Each stage embodied the cumulative occurrence of co-existing diseases, depicted as nodes on the tree, with edges symbolizing potential transitions between these linked nodes. Our model identified eight distinct ALS patient trajectories, unveiling unique patterns of disease associations at various stages of progression. These patterns may suggest underlying disease mechanisms or risk factors. This research re-conceptualizes ALS progression as a migration through diverse stages, instead of the perspective of a sequence of isolated events. This new approach illuminates patterns of disease association across different progression phases. The insights obtained from this study hold the potential to inform doctors regarding the development of personalized treatment strategies, ultimately enhancing patient prognosis and quality of life.}, } @article {pmid37892126, year = {2023}, author = {Ramos, V and Reis, M and Ferreira, L and Silva, AM and Ferraz, R and Vieira, M and Vasconcelos, V and Martins, R}, title = {Stalling the Course of Neurodegenerative Diseases: Could Cyanobacteria Constitute a New Approach toward Therapy?.}, journal = {Biomolecules}, volume = {13}, number = {10}, pages = {}, pmid = {37892126}, issn = {2218-273X}, mesh = {Humans ; *Neurodegenerative Diseases/metabolism ; Oxidative Stress ; *Parkinson Disease/drug therapy ; Antioxidants/pharmacology ; *Cyanobacteria/metabolism ; }, abstract = {Neurodegenerative diseases (NDs) are characterized by progressive and irreversible neuronal loss, accompanied by a range of pathological pathways, including aberrant protein aggregation, altered energy metabolism, excitotoxicity, inflammation, and oxidative stress. Some of the most common NDs include Alzheimer's Disease (AD), Parkinson's Disease (PD), Multiple Sclerosis (MS), Amyotrophic Lateral Sclerosis (ALS), and Huntington's Disease (HD). There are currently no available cures; there are only therapeutic approaches that ameliorate the progression of symptoms, which makes the search for new drugs and therapeutic targets a constant battle. Cyanobacteria are ancient prokaryotic oxygenic phototrophs whose long evolutionary history has resulted in the production of a plethora of biomedically relevant compounds with anti-inflammatory, antioxidant, immunomodulatory, and neuroprotective properties, that can be valuable in this field. This review summarizes the major NDs and their pathophysiology, with a focus on the anti-neurodegenerative properties of cyanobacterial compounds and their main effects.}, } @article {pmid37891975, year = {2023}, author = {Fu, RH and Chen, HJ and Hong, SY}, title = {Glycine-Alanine Dipeptide Repeat Protein from C9-ALS Interacts with Sulfide Quinone Oxidoreductase (SQOR) to Induce the Activity of the NLRP3 Inflammasome in HMC3 Microglia: Irisflorentin Reverses This Interaction.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {12}, number = {10}, pages = {}, pmid = {37891975}, issn = {2076-3921}, support = {MOST 105-2314-B-039-017-MY3//the Ministry of Science and Technology (Taiwan)/ ; DMR-111-140//China Medical University Hospital (Taiwan)/ ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal rare disease of progressive degeneration of motor neurons. The most common genetic mutation in ALS is the hexanucleotide repeat expansion (HRE) located in the first intron of the C9orf72 gene (C9-ALS). HRE can produce dipeptide repeat proteins (DPRs) such as poly glycine-alanine (GA) in a repeat-associated non-ATG (RAN) translation. GA-DPR has been shown to be toxic to motor neurons in various biological models. However, its effects on microglia involved in C9-ALS have not been reported. Here, we show that GA-DPR (GA50) activates the NLR family pyrin domain containing 3 (NLRP3) inflammasome in a human HMC3 microglia model. MCC950 (specific inhibitor of the NLRP3) treatment can abrogate this activity. Next, using yeast two-hybrid screening, we identified sulfide quinone oxidoreductase (SQOR) as a GA50 interacting protein. SQOR knockdown in HMC3 cells can significantly induce the activity of the NLRP3 inflammasome by upregulating the level of intracellular reactive oxygen species and the cytoplasmic escape of mitochondrial DNA. Furthermore, we obtained irisflorentin as an effective blocker of the interaction between SQOR and GA50, thus inhibiting NLRP3 inflammasome activity in GA50-expressing HMC3 cells. These results imply the association of GA-DPR, SQOR, and NLRP3 inflammasomes in microglia and establish a treatment strategy for C9-ALS with irisflorentin.}, } @article {pmid37891966, year = {2023}, author = {Grossini, E and De Marchi, F and Venkatesan, S and Mele, A and Ferrante, D and Mazzini, L}, title = {Effects of Acetyl-L-Carnitine on Oxidative Stress in Amyotrophic Lateral Sclerosis Patients: Evaluation on Plasma Markers and Members of the Neurovascular Unit.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {12}, number = {10}, pages = {}, pmid = {37891966}, issn = {2076-3921}, abstract = {Oxidative stress, the alteration of mitochondrial function, and the neurovascular unit (NVU), play a role in Amyotrophic Lateral Sclerosis (ALS) pathogenesis. We aimed to demonstrate the changes in the plasma redox system and nitric oxide (NO) in 32 new ALS-diagnosed patients in treatment with Acetyl-L-Carnitine (ALCAR) compared to healthy controls. We also evaluated the effects of plasma on human umbilical cord-derived endothelial vascular cells (HUVEC) and astrocytes. The analyses were performed at the baseline (T0), after three months (T1), and after six months (T2). In ALS patients at T0/T1, the plasma markers of lipid peroxidation, thiobarbituric acid reactive substances (TBARS) and 4-hydroxy nonenal (4-HNE) were higher, whereas the antioxidants, glutathione (GSH) and the glutathione peroxidase (GPx) activity were lower than in healthy controls. At T2, plasma TBARS and 4-HNE decreased, whereas plasma GSH and the GPx activity increased in ALS patients. As regards NO, the plasma levels were firmly lower at T0-T2 than those of healthy controls. Cell viability, and mitochondrial membrane potential in HUVEC/astrocytes treated with the plasma of ALS patients at T0-T2 were reduced, while the oxidant release increased. Those results, which confirmed the fundamental role of oxidative stress, mitochondrial function, and of the NVU in ALS pathogenesis, can have a double meaning, acting as disease markers at baseline and potential markers of drug effects in clinical practice and during clinical trials.}, } @article {pmid37891890, year = {2023}, author = {Korczowska-Łącka, I and Słowikowski, B and Piekut, T and Hurła, M and Banaszek, N and Szymanowicz, O and Jagodziński, PP and Kozubski, W and Permoda-Pachuta, A and Dorszewska, J}, title = {Disorders of Endogenous and Exogenous Antioxidants in Neurological Diseases.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {12}, number = {10}, pages = {}, pmid = {37891890}, issn = {2076-3921}, abstract = {In diseases of the central nervous system, such as Alzheimer's disease (AD), Parkinson's disease (PD), stroke, amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), and even epilepsy and migraine, oxidative stress load commonly surpasses endogenous antioxidative capacity. While oxidative processes have been robustly implicated in the pathogenesis of these diseases, the significance of particular antioxidants, both endogenous and especially exogenous, in maintaining redox homeostasis requires further research. Among endogenous antioxidants, enzymes such as catalase, superoxide dismutase, and glutathione peroxidase are central to disabling free radicals, thereby preventing oxidative damage to cellular lipids, proteins, and nucleic acids. Whether supplementation with endogenously occurring antioxidant compounds such as melatonin and glutathione carries any benefit, however, remains equivocal. Similarly, while the health benefits of certain exogenous antioxidants, including ascorbic acid (vitamin C), carotenoids, polyphenols, sulforaphanes, and anthocyanins are commonly touted, their clinical efficacy and effectiveness in particular neurological disease contexts need to be more robustly defined. Here, we review the current literature on the cellular mechanisms mitigating oxidative stress and comment on the possible benefit of the most common exogenous antioxidants in diseases such as AD, PD, ALS, HD, stroke, epilepsy, and migraine. We selected common neurological diseases of a basically neurodegenerative nature.}, } @article {pmid37891753, year = {2023}, author = {Rostás, R and Fekete, I and Horváth, L and Fekete, K}, title = {Blink Reflex Examination in Patients with Amyotrophic Lateral Sclerosis Compared to Diseases Affecting the Peripheral Nervous System and Healthy Controls.}, journal = {Brain sciences}, volume = {13}, number = {10}, pages = {}, pmid = {37891753}, issn = {2076-3425}, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal form of neuromuscular disease. The aim of this study was to assess changes in the blink reflex (BR) parameters as a valid and easy-to-use tool in ALS patients. We assessed the BR test in patients with a definitive diagnosis of ALS, healthy volunteers, and patients with diseases affecting the peripheral nervous system. The BR was studied in 29 patients who met the Awaji criteria. Latencies were compared with our healthy controls (N = 50) and other diseases of the peripheral nervous system (N = 61). The ALS Functional Rating Scale-Revised (ALSFRS-R) was used to evaluate functional status. Significantly prolonged R2i and R2c latencies were found in the ALS group compared with the healthy control group (p < 0.001). The latencies of R1, R2i, R2c were all increased in the bulbar subtype compared to the limb-onset subtype (p < 0.05). According to our results, BR examination might be a promising tool to monitor the course of the disease or serve as a prognostic biomarker in patients with ALS, but it should be assessed in further studies. The abnormalities detected through BR might help perform earlier interventions in ALS patients and might be useful in other diseases affecting the peripheral nervous system.}, } @article {pmid37891396, year = {2023}, author = {Carey, LB and Bambling, M and Hodgson, TJ and Jamieson, N and Bakhurst, MG and Koenig, HG}, title = {Pastoral Narrative Disclosure: The Development and Evaluation of an Australian Chaplaincy Intervention Strategy for Addressing Moral Injury.}, journal = {Journal of religion and health}, volume = {62}, number = {6}, pages = {4032-4071}, pmid = {37891396}, issn = {1573-6571}, mesh = {Humans ; *Stress Disorders, Post-Traumatic ; Australia ; *Veterans ; Morals ; Narration ; *Pastoral Care/methods ; Clergy ; *Chaplaincy Service, Hospital ; Spirituality ; }, abstract = {This paper describes the development and initial chaplaincy user evaluation of 'Pastoral Narrative Disclosure' (PND) as a rehabilitation strategy developed for chaplains to address moral injury among veterans. PND is an empirically informed and integrated intervention comprising eight stages of pastoral counselling, guidance and education that was developed by combining two previously existing therapeutic techniques, namely Litz et al's (2017) 'Adaptive Disclosure' and 'Confessional Practice' (Joob & Kettunen, 2013). The development and results of PND can be categorized into five phases. Phase 1: PND Strategy Formation-based upon extensive international research demonstrating that MI is a complex bio-psycho-social-spiritual syndrome with symptoms sufficiently distinct from post-traumatic stress disorder. The review also provided evidence of the importance of chaplains being involved in moral injury rehabilitation. Phase II: Development and Implementation of 'Moral Injury Skills Training' (MIST)-which involved the majority of available Australian Defence Force (ADF) Chaplains (n = 242/255: 94.9%) completing a basic 'Introduction to Moral Injury' (MIST-1) as well as an 'Introduction to PND' (MIST-2). Phase III: MIST-3-PND-Pilot evaluation-involved a representative chaplaincy cohort (n = 13) undergoing the PND eight-stage strategy to ensure the integrity and quality of PND from a chaplaincy perspective prior to wider implementation. The pilot PND evaluation indicated a favourable satisfaction rating (n = 11/13: 84.6%; M = 4.73/5.0 satisfaction). Phase IV: MIST-3-PND Implementation-involved a larger cohort of ADF Chaplaincy participants (n = 210) completing a revised and finalized PND strategy which was regarded favourably by the majority of ADF Chaplains (n = 201/210: 95.7%; M = 4.73/5.0 satisfaction). Phase V: Summation. In conclusion the positive satisfaction ratings by a significant number of ADF chaplaincy personnel completing MIST-3-PND, provided evidence that chaplains evaluated PND as a suitable counselling, guidance and education strategy, which affirmed its utilisation and justifies further research for using PND to address MI among veterans, that may also prove valuable for other chaplains working in community health and first responder contexts.}, } @article {pmid37890889, year = {2023}, author = {Ilieva, H and Vullaganti, M and Kwan, J}, title = {Advances in molecular pathology, diagnosis, and treatment of amyotrophic lateral sclerosis.}, journal = {BMJ (Clinical research ed.)}, volume = {383}, number = {}, pages = {e075037}, pmid = {37890889}, issn = {1756-1833}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/genetics/therapy ; Pathology, Molecular ; Disease Progression ; }, abstract = {Although the past two decades have produced exciting discoveries in the genetics and pathology of amyotrophic lateral sclerosis (ALS), progress in developing an effective therapy remains slow. This review summarizes the critical discoveries and outlines the advances in disease characterization, diagnosis, imaging, and biomarkers, along with the current status of approaches to ALS care and treatment. Additional knowledge of the factors driving disease progression and heterogeneity will hopefully soon transform the care for patients with ALS into an individualized, multi-prong approach able to prevent disease progression sufficiently to allow for a dignified life with limited disability.}, } @article {pmid37889424, year = {2024}, author = {Yan, Z and Xu, Y and Li, K and Liu, L}, title = {Association between genetically proxied lipid-lowering drug targets, lipid traits, and amyotrophic lateral sclerosis: a mendelian randomization study.}, journal = {Acta neurologica Belgica}, volume = {124}, number = {2}, pages = {485-494}, pmid = {37889424}, issn = {2240-2993}, support = {No. 81860826//National Natural Science Foundation of China/ ; }, mesh = {Humans ; Cholesterol, LDL/genetics ; *Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use ; *Amyotrophic Lateral Sclerosis/genetics ; Mendelian Randomization Analysis ; Apolipoproteins B/genetics ; Polymorphism, Single Nucleotide ; }, abstract = {BACKGROUND: The use of circulating lipid traits as biomarkers to predict the risk of amyotrophic lateral sclerosis (ALS) is currently controversial, and the evidence-based medical evidence for the use of lipid-lowering agents, especially statins, on ALS risk remains insufficient. Our aim was to apply a Mendelian randomization (MR) approach to assess the causal impact of lipid-lowering agents and circulating lipid traits on ALS risk.

MATERIALS AND METHODS: Our study included primary and secondary analyses, in which the risk associations of lipid-lowering gene inhibitors, lipid traits, and ALS were assessed by the inverse variance weighting method as the primary approach. The robustness of the results was assessed using LDSC assessment, conventional MR sensitivity analysis, and used Mediating MR to explore potential mechanisms of occurrence. In the secondary analysis, the association of lipid-lowering genes with ALS was validated using the Summary data-based Mendelian Randomization (SMR) method.

RESULTS: Our results showed strong evidence between genetic proxies for Apolipoprotein B (ApoB) inhibitor (OR = 0.76, 95% CI = 0.68 - 0.86; P = 5.58 × 10[-6]) and reduced risk of ALS. Additionally, 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) inhibitor (OR = 1.06, 95% CI = 0. 85-1.33) was not found to increase ALS risk. SMR results suggested that ApoB expression was associated with increased ALS risk, and colocalization analysis did not support a significant common genetic variation between ApoB and ALS. Mediator MR analysis suggested a possible mediating role for interleukin-6 and low-density lipoprotein cholesterol (LDL-C). While elevated LDL-C was significantly associated with increased risk of ALS among lipid traits, total cholesterol (TC) and ApoB were weakly associated with ALS. LDSC results suggested a potential genetic correlation between these lipid traits and ALS.

CONCLUSIONS: Using ApoB inhibitor can lower the risk of ALS, statins do not trigger ALS, and LDL-C, TC, and ApoB levels can predict the risk of ALS.}, } @article {pmid37889099, year = {2023}, author = {Liddell, JR and Hilton, JBW and Crouch, PJ}, title = {Cu[II](atsm) significantly decreases microglial reactivity in patients with sporadic amyotrophic lateral sclerosis.}, journal = {Neuropathology and applied neurobiology}, volume = {49}, number = {5}, pages = {e12938}, doi = {10.1111/nan.12938}, pmid = {37889099}, issn = {1365-2990}, support = {//National Health and Medical Research Council/ ; }, mesh = {Animals ; Humans ; Mice ; *Amyotrophic Lateral Sclerosis ; Microglia ; Copper ; Mice, Transgenic ; }, } @article {pmid37887472, year = {2023}, author = {Palazzo, L and Pizzolato, L and Rigo, M and Bondì, G}, title = {Amyotrophic Lateral Sclerosis and Its Management during the COVID-19 Pandemic: A Qualitative Study with Thematic Analysis of Patients and Caregivers Who Participated in Self-Help Groups.}, journal = {Behavioral sciences (Basel, Switzerland)}, volume = {13}, number = {10}, pages = {}, pmid = {37887472}, issn = {2076-328X}, abstract = {This study employs a qualitative methodology to explore the effects of the pandemic on the lives of ALS patients and their caregivers. It aims to understand whether and how online self-help groups have assisted families dealing with amyotrophic lateral sclerosis (ALS) patients. ALS is a neurodegenerative disease with both physical and psychosocial implications. Consequently, it significantly affects the lives of patients' caregivers. In 2020, the COVID-19 pandemic exacerbated this situation. The results show that the pandemic has had a negative impact on the well-being of ALS caregivers and patients. Furthermore, bereavement and death were dealt with in different ways by the families involved. The pandemic aggravated the health of ALS patients and increased the workload of their caregivers; however, online psychological support was appreciated for its role in providing emotional help and diminishing social isolation.}, } @article {pmid37887320, year = {2023}, author = {Fu, RH and Chen, HJ and Hong, SY}, title = {Interaction of the C9orf72-Amyotrophic Lateral Sclerosis-Related Proline-Arginine Dipeptide Repeat Protein with the RNA-Binding Protein NOVA1 Causes Decreased Expression of UNC13A Due to Enhanced Inclusion of Cryptic Exons, Which Is Reversed by Betulin Treatment.}, journal = {Cells}, volume = {12}, number = {20}, pages = {}, pmid = {37887320}, issn = {2073-4409}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy/genetics/metabolism ; Arginine/metabolism ; C9orf72 Protein/genetics/metabolism ; Dipeptides/metabolism ; Motor Neurons/pathology ; Neuro-Oncological Ventral Antigen ; Proline/metabolism ; RNA, Messenger/genetics/metabolism ; RNA-Binding Proteins/genetics/metabolism ; }, abstract = {C9orf72 mutations are the most common form of familial amyotrophic lateral sclerosis (C9-ALS). It causes the production of proline-arginine dipeptide repeat proteins (PR-DPRs) in motor neurons (MNs), leading to the molecular pathology characteristic of ALS. UNC13A is critical for maintaining the synaptic function of MNs. Most ALS patients have nuclear deletion of the splicing repressor TDP-43 in MNs, which causes inclusion of the cryptic exon (CE) of UNC13A mRNA, resulting in nonsense-mediated mRNA decay and reduced protein expression. Therefore, in this study, we explored the role of PR-DPR in CE inclusion of UNC13A mRNA. Our results showed that PR-DPR (PR50) induced CE inclusion and decreased the protein expression of UNC13A in human neuronal cell lines. We also identified an interaction between the RNA-binding protein NOVA1 and PR50 by yeast two-hybrid screening. NOVA1 expression is known to be reduced in patients with ALS. We found that knockdown of NOVA1 enhanced CE inclusion of UNC13A mRNA. Furthermore, the naturally occurring triterpene betulin can inhibit the interaction between NOVA1 and PR50, thus preventing CE inclusion of UNC13A mRNA and protein reduction in human neuronal cell lines. This study linked PR-DPR with CE inclusion of UNC13A mRNA and developed candidate therapeutic strategies for C9-ALS using betulin.}, } @article {pmid37887305, year = {2023}, author = {Provasek, VE and Kodavati, M and Guo, W and Wang, H and Boldogh, I and Van Den Bosch, L and Britz, G and Hegde, ML}, title = {lncRNA Sequencing Reveals Neurodegeneration-Associated FUS Mutations Alter Transcriptional Landscape of iPS Cells That Persists in Motor Neurons.}, journal = {Cells}, volume = {12}, number = {20}, pages = {}, pmid = {37887305}, issn = {2073-4409}, support = {RF1NS112719/NS/NINDS NIH HHS/United States ; R01 NS094535/NS/NINDS NIH HHS/United States ; R03AG064266/NH/NIH HHS/United States ; R01NS094535/NH/NIH HHS/United States ; R01 NS088645/NS/NINDS NIH HHS/United States ; R03 AG064266/AG/NIA NIH HHS/United States ; RF1 NS112719/NS/NINDS NIH HHS/United States ; R01NS088645/NH/NIH HHS/United States ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/metabolism ; *Induced Pluripotent Stem Cells/metabolism ; *RNA, Long Noncoding/genetics/metabolism ; Motor Neurons/metabolism ; Mutation/genetics ; RNA-Binding Protein FUS/genetics/metabolism ; }, abstract = {Fused-in sarcoma (FUS) gene mutations have been implicated in amyotrophic lateral sclerosis (ALS). This study aimed to investigate the impact of FUS mutations (R521H and P525L) on the transcriptome of induced pluripotent stem cells (iPSCs) and iPSC-derived motor neurons (iMNs). Using RNA sequencing (RNA Seq), we characterized differentially expressed genes (DEGs) and differentially expressed lncRNAs (DELs) and subsequently predicted lncRNA-mRNA target pairs (TAR pairs). Our results show that FUS mutations significantly altered the expression profiles of mRNAs and lncRNAs in iPSCs. Using this large dataset, we identified and verified six key differentially regulated TAR pairs in iPSCs that were also altered in iMNs. These target transcripts included: GPR149, NR4A, LMO3, SLC15A4, ZNF404, and CRACD. These findings indicated that selected mutant FUS-induced transcriptional alterations persist from iPSCs into differentiated iMNs. Functional enrichment analyses of DEGs indicated pathways associated with neuronal development and carcinogenesis as likely altered by these FUS mutations. Furthermore, ingenuity pathway analysis (IPA) and GO network analysis of lncRNA-targeted mRNAs indicated associations between RNA metabolism, lncRNA regulation, and DNA damage repair. Our findings provide insights into potential molecular mechanisms underlying the pathophysiology of ALS-associated FUS mutations and suggest potential therapeutic targets for the treatment of ALS.}, } @article {pmid37887017, year = {2023}, author = {You, J and Youssef, MMM and Santos, JR and Lee, J and Park, J}, title = {Microglia and Astrocytes in Amyotrophic Lateral Sclerosis: Disease-Associated States, Pathological Roles, and Therapeutic Potential.}, journal = {Biology}, volume = {12}, number = {10}, pages = {}, pmid = {37887017}, issn = {2079-7737}, abstract = {Microglial and astrocytic reactivity is a prominent feature of amyotrophic lateral sclerosis (ALS). Microglia and astrocytes have been increasingly appreciated to play pivotal roles in disease pathogenesis. These cells can adopt distinct states characterized by a specific molecular profile or function depending on the different contexts of development, health, aging, and disease. Accumulating evidence from ALS rodent and cell models has demonstrated neuroprotective and neurotoxic functions from microglia and astrocytes. In this review, we focused on the recent advancements of knowledge in microglial and astrocytic states and nomenclature, the landmark discoveries demonstrating a clear contribution of microglia and astrocytes to ALS pathogenesis, and novel therapeutic candidates leveraging these cells that are currently undergoing clinical trials.}, } @article {pmid37886540, year = {2023}, author = {Snyder, A and Ryan, VH and Hawrot, J and Lawton, S and Ramos, DM and Qi, YA and Johnson, K and Reed, X and Johnson, NL and Kollasch, AW and Duffy, M and VandeVrede, L and Cochran, JN and Miller, BL and Toro, C and Bielekova, B and Yokoyama, JS and Marks, DS and Kwan, JY and Cookson, MR and Ward, ME}, title = {An ANXA11 P93S variant dysregulates TDP-43 and causes corticobasal syndrome.}, journal = {Research square}, volume = {}, number = {}, pages = {}, pmid = {37886540}, issn = {2693-5015}, support = {P50 AG023501/AG/NIA NIH HHS/United States ; 75N95022C00031/DA/NIDA NIH HHS/United States ; K01 AG049152/AG/NIA NIH HHS/United States ; R01 AG062588/AG/NIA NIH HHS/United States ; FI2 GM142475/GM/NIGMS NIH HHS/United States ; U54 NS123985/NS/NINDS NIH HHS/United States ; U19 AG079774/AG/NIA NIH HHS/United States ; P30 AG062422/AG/NIA NIH HHS/United States ; P01 AG019724/AG/NIA NIH HHS/United States ; R01 AG057234/AG/NIA NIH HHS/United States ; ZIA AG000534/ImNIH/Intramural NIH HHS/United States ; ZIA AG000539/ImNIH/Intramural NIH HHS/United States ; R00 AG068271/AG/NIA NIH HHS/United States ; K23 AG073514/AG/NIA NIH HHS/United States ; }, abstract = {As genetic testing has become more accessible and affordable, variants of uncertain significance (VUS) are increasingly identified, and determining whether these variants play causal roles in disease is a major challenge. The known disease-associated Annexin A11 (ANXA11) mutations result in ANXA11 aggregation, alterations in lysosomal-RNA granule co-trafficking, and TDP-43 mis-localization and present as amyotrophic lateral sclerosis or frontotemporal dementia. We identified a novel VUS in ANXA11 (P93S) in a kindred with corticobasal syndrome and unique radiographic features that segregated with disease. We then queried neurodegenerative disorder clinic databases to identify the phenotypic spread of ANXA11 mutations. Multi-modal computational analysis of this variant was performed and the effect of this VUS on ANXA11 function and TDP-43 biology was characterized in iPSC-derived neurons. Single-cell sequencing and proteomic analysis of iPSC-derived neurons and microglia were used to determine the multiomic signature of this VUS. Mutations in ANXA11 were found in association with clinically diagnosed corticobasal syndrome, thereby establishing corticobasal syndrome as part of ANXA11 clinical spectrum. In iPSC-derived neurons expressing mutant ANXA11, we found decreased colocalization of lysosomes and decreased neuritic RNA as well as decreased nuclear TDP-43 and increased formation of cryptic exons compared to controls. Multiomic assessment of the P93S variant in iPSC-derived neurons and microglia indicates that the pathogenic omic signature in neurons is modest compared to microglia. Additionally, omic studies reveal that immune dysregulation and interferon signaling pathways in microglia are central to disease. Collectively, these findings identify a new pathogenic variant in ANXA11, expand the range of clinical syndromes caused by ANXA11 mutations, and implicate both neuronal and microglia dysfunction in ANXA11 pathophysiology. This work illustrates the potential for iPSC-derived cellular models to revolutionize the variant annotation process and provides a generalizable approach to determining causality of novel variants across genes.}, } @article {pmid37885757, year = {2023}, author = {Krannich, T and Sarrias, MH and Ben Aribi, H and Shokrof, M and Iacoangeli, A and Al-Chalabi, A and Sedlazeck, FJ and Busby, B and Al Khleifat, A}, title = {VariantSurvival: a tool to identify genotype-treatment response.}, journal = {Frontiers in bioinformatics}, volume = {3}, number = {}, pages = {1277923}, pmid = {37885757}, issn = {2673-7647}, support = {/WT_/Wellcome Trust/United Kingdom ; MR/L501529/1/MRC_/Medical Research Council/United Kingdom ; }, abstract = {Motivation: For a number of neurological diseases, such as Alzheimer's disease, amyotrophic lateral sclerosis, and many others, certain genes are known to be involved in the disease mechanism. A common question is whether a structural variant in any such gene may be related to drug response in clinical trials and how this relationship can contribute to the lifecycle of drug development. Results: To this end, we introduce VariantSurvival, a tool that identifies changes in survival relative to structural variants within target genes. VariantSurvival matches annotated structural variants with genes that are clinically relevant to neurological diseases. A Cox regression model determines the change in survival between the placebo and clinical trial groups with respect to the number of structural variants in the drug target genes. We demonstrate the functionality of our approach with the exemplary case of the SETX gene. VariantSurvival has a user-friendly and lightweight graphical user interface built on the shiny web application package.}, } @article {pmid37885418, year = {2023}, author = {Biebelberg, B and Klompas, M and Rhee, C}, title = {The authors' reply to Schaffzin et al's Letter to the Editor.}, journal = {Infection control and hospital epidemiology}, volume = {44}, number = {12}, pages = {2098}, doi = {10.1017/ice.2023.222}, pmid = {37885418}, issn = {1559-6834}, } @article {pmid37885330, year = {2023}, author = {Lunghi, G and Di Biase, E and Carsana, EV and Henriques, A and Callizot, N and Mauri, L and Ciampa, MG and Mari, L and Loberto, N and Aureli, M and Sonnino, S and Spedding, M and Chiricozzi, E and Fazzari, M}, title = {GM1 ganglioside exerts protective effects against glutamate-excitotoxicity via its oligosaccharide in wild-type and amyotrophic lateral sclerosis motor neurons.}, journal = {FEBS open bio}, volume = {13}, number = {12}, pages = {2324-2341}, pmid = {37885330}, issn = {2211-5463}, support = {//Banca d'Italia/ ; 200045//Mizutani Foundation for Glycoscience/ ; //APC central fund of the University of Milan/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy/metabolism ; G(M1) Ganglioside/pharmacology/metabolism ; Glutamic Acid ; *Neurodegenerative Diseases/metabolism ; Superoxide Dismutase/metabolism ; Motor Neurons/metabolism ; }, abstract = {Alterations in glycosphingolipid metabolism have been linked to the pathophysiological mechanisms of amyotrophic lateral sclerosis (ALS), a neurodegenerative disease affecting motor neurons. Accordingly, administration of GM1, a sialic acid-containing glycosphingolipid, is protective against neuronal damage and supports neuronal homeostasis, with these effects mediated by its bioactive component, the oligosaccharide head (GM1-OS). Here, we add new evidence to the therapeutic efficacy of GM1 in ALS: Its administration to WT and SOD1[G93A] motor neurons affected by glutamate-induced excitotoxicity significantly increased neuronal survival and preserved neurite networks, counteracting intracellular protein accumulation and mitochondria impairment. Importantly, the GM1-OS faithfully replicates GM1 activity, emphasizing that even in ALS the protective function of GM1 strictly depends on its pentasaccharide.}, } @article {pmid37882882, year = {2023}, author = {Wang, Y and Sun, S and Zhai, J and Liu, Y and Song, C and Sun, C and Li, Q and Liu, J and Jiang, H and Liu, Y}, title = {scAAV9-VEGF alleviates symptoms of amyotrophic lateral sclerosis (ALS) mice through regulating aromatase.}, journal = {Experimental brain research}, volume = {241}, number = {11-12}, pages = {2817-2827}, pmid = {37882882}, issn = {1432-1106}, support = {ZR2020QH126//Natural Science Foundation of Shandong Province Youth Fund/ ; ZR2020QH124//Natural Science Foundation of Shandong Province Youth Fund/ ; 2019ZC010137//Zibo city key research and development plan/ ; 2021Q048//TCM science and technology Project of Shandong Province/ ; }, mesh = {Mice ; Animals ; *Amyotrophic Lateral Sclerosis/drug therapy/metabolism ; Motor Neurons/physiology ; Vascular Endothelial Growth Factor A/metabolism/pharmacology ; *Neurodegenerative Diseases/metabolism ; Aromatase/genetics/metabolism/pharmacology ; Superoxide Dismutase/genetics/metabolism/pharmacology ; Mice, Transgenic ; Disease Models, Animal ; Estrogens/pharmacology/therapeutic use ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is an adult-onset, chronic, progressive, and fatal neurodegenerative disease that leads to progressive atrophy and weakness of the muscles throughout the body. Herein, we found that the intrathecal injection of adeno-associated virus (AAV)-delivered VEGF in SOD1-G93A transgenic mice, as well as ALS mice, could significantly delay disease onset and preserve motor functions and neurological functions, thus prolonging the survival of mice models. Moreover, we found that VEGF treatment could induce the elevated expression of aromatase, which is a key enzyme in estrogen synthesis, in neurons but not in astrocytes. On the other hand, the changes in the expression of oxidative stress-related factors HO-1 and GCLM and autophagy-related proteins p62 and LC3II upon the administration of VEGF revealed the involvement of oxidative stress and autophagy underlying the downstream of the VEGF-induced mitigation of ALS. In conclusion, this study proved the protective effects of VEGF in the onset and development of ALS and revealed the involvement of estrogen, oxidative stress and autophagy in the VEGF-induced alleviation of ALS. Our results highlighted the potential of VEGF as a promising therapeutic agent in the treatment of ALS.}, } @article {pmid37882537, year = {2024}, author = {Hung, C and Patani, R}, title = {Elevated 4R tau contributes to endolysosomal dysfunction and neurodegeneration in VCP-related frontotemporal dementia.}, journal = {Brain : a journal of neurology}, volume = {147}, number = {3}, pages = {970-979}, pmid = {37882537}, issn = {1460-2156}, support = {/WT_/Wellcome Trust/United Kingdom ; MR/S006591/1/MRC_/Medical Research Council/United Kingdom ; /CRUK_/Cancer Research UK/United Kingdom ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics ; *Frontotemporal Dementia/genetics ; *Induced Pluripotent Stem Cells ; Lysosomes ; *Valosin Containing Protein/genetics ; }, abstract = {Frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) are two incurable neurodegenerative diseases that exist on a clinical, genetic and pathological spectrum. The VCP gene is highly relevant, being directly implicated in both FTD and ALS. Here, we investigate the effects of VCP mutations on the cellular homoeostasis of human induced pluripotent stem cell-derived cortical neurons, focusing on endolysosomal biology and tau pathology. We found that VCP mutations cause abnormal accumulation of enlarged endolysosomes accompanied by impaired interaction between two nuclear RNA binding proteins: fused in sarcoma (FUS) and splicing factor, proline- and glutamine-rich (SFPQ) in human cortical neurons. The spatial dissociation of intranuclear FUS and SFPQ correlates with alternative splicing of the MAPT pre-mRNA and increased tau phosphorylation. Importantly, we show that inducing 4R tau expression using antisense oligonucleotide technology is sufficient to drive neurodegeneration in control human neurons, which phenocopies VCP-mutant neurons. In summary, our findings demonstrate that tau hyperphosphorylation, endolysosomal dysfunction, lysosomal membrane rupture, endoplasmic reticulum stress and apoptosis are driven by a pathogenic increase in 4R tau.}, } @article {pmid37882288, year = {2023}, author = {Barco-Antoñanzas, M and Font-Farre, M and Eceiza, MV and Gil-Monreal, M and van der Hoorn, RAL and Royuela, M and Zabalza, A}, title = {Cysteine proteases are activated in sensitive Amaranthus palmeri populations upon treatment with herbicides inhibiting amino acid biosynthesis.}, journal = {Physiologia plantarum}, volume = {175}, number = {5}, pages = {e13993}, doi = {10.1111/ppl.13993}, pmid = {37882288}, issn = {1399-3054}, support = {//Eusko Jaurlaritza/ ; 2020 117723-RB-100//Ministerio de Ciencia e Innovación/ ; AGL2016-77531-R//Ministerio de Economía y Competitividad/ ; }, mesh = {Herbicide Resistance ; *Amaranthus/metabolism ; *Herbicides/pharmacology/metabolism ; *Cysteine Proteases/metabolism/pharmacology ; }, abstract = {The herbicides glyphosate and pyrithiobac inhibit the enzyme 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) in the aromatic amino acid biosynthetic pathway and acetolactate synthase (ALS) in the branched-chain amino acid biosynthetic pathway, respectively. Here we characterise the protease activity profiles of a sensitive (S), a glyphosate-resistant (GR) and a multiple-resistant (MR) population of Amaranthus palmeri in response to glyphosate and pyrithiobac. Amino acid accumulation and cysteine protease activities were induced with both herbicides in the S population and with pyrithiobac in the GR population, suggesting that the increase in cysteine proteases is responsible for the increased degradation of the available proteins and the observed increase in free amino acids. Herbicides did not induce any changes in the proteolytic activities in the populations with target-site resistance, indicating that this effect was only induced in sensitive plants.}, } @article {pmid37881503, year = {2023}, author = {Petrashen, AP and Lin, Y and Kun, B and Kreiling, JA}, title = {A cluster of X-linked miRNAs are de-repressed with age in mouse liver and target growth hormone signaling.}, journal = {Frontiers in aging}, volume = {4}, number = {}, pages = {1261121}, pmid = {37881503}, issn = {2673-6217}, support = {P20 GM119943/GM/NIGMS NIH HHS/United States ; T32 AG041688/AG/NIA NIH HHS/United States ; T32 GM136566/GM/NIGMS NIH HHS/United States ; }, abstract = {Growth hormone (GH) signaling influences lifespan in a wide variety of mammalian species. We previously reported that a cluster of miRNAs located on the X-chromosome are de-repressed with age in male mouse liver, and a subset, the mir-465 family, can directly attenuate expression of the growth hormone receptor (GHR) in vitro leading to a reduction in GH signaling. Here we show that this cluster of miRNAs is also upregulated in the liver with age in females, and that calorie restriction and the Ames dwarf genotype, both known to delay aging, attenuate the upregulation of the miRNA cluster. Upregulation of mir-465 in vivo leads to a reduction in GHR mRNA in the liver and an attenuation of GH signaling, indicated by a reduction in GHR, IGF-1, IGFBP3, and ALS mRNA expression. There is a corresponding reduction in IGF-1 protein levels in the liver and plasma. These results suggest that the age-associated upregulation of the X-chromosomal cluster of miRNAs could influence lifespan.}, } @article {pmid37881309, year = {2023}, author = {Li, T and Ye, M and Yang, G and Diao, S and Zhou, Y and Qin, Y and Ding, D and Zhu, M and Fang, Q}, title = {Regional white matter hyperintensity volume predicts persistent cognitive impairment in acute lacunar infarct patients.}, journal = {Frontiers in neurology}, volume = {14}, number = {}, pages = {1265743}, pmid = {37881309}, issn = {1664-2295}, abstract = {BACKGROUND: White matter hyperintensity (WMH) is often described in acute lacunar stroke (ALS) patients. However, the specific relationship between regional WMH volume and persistent cognitive impairment remains unclear.

METHODS: We enrolled patients with ALS who were hospitalized at the First Affiliated Hospital of Soochow University between January 2020 and November 2022. All patients were assessed for global cognitive function using the Montreal Cognitive Assessment (MoCA) scale at 14 ± 2 days and 6 months after the onset of ALS. Manifestations of chronic cerebral small vessel disease (CSVD) were assessed via MRI scan. The distributions of regional WMH were segmented, and their relationship with cognitive impairment was evaluated.

RESULTS: A total of 129 patients were enrolled. Baseline frontal WMH volume (OR = 1.18, P = 0.04) was an independent risk factor for long-term cognitive impairment after ALS. Furthermore, the presence of WMH at the genu of the corpus callosum (GCC) at baseline (OR = 3.1, P = 0.033) was strongly associated with persistent cognitive decline. Multivariable logistic regression analysis showed that depression (OR = 6.252, P = 0.029), NIHSS score (OR = 1.24, P = 0.011), and albumin at admission (OR = 0.841, P = 0.032) were also important determinants of long-term cognitive impairment after ALS.

CONCLUSIONS: Our study found that WMH, especially frontal WMH volume and the presence of WMH at the GCC at baseline, independently contributed to long-term cognitive decline in ALS patients. This study provides new evidence of the clinical relationship between regional WMH volume and cognitive impairment in ALS patients.}, } @article {pmid37880984, year = {2024}, author = {Menon, D and Nashi, S and Mohanty, M and Dubbal, R and Mk, F and Vengalil, S and Thomas, A and Kumar, V and Baskar, D and Arunachal, G and Nalini, A}, title = {A novel DHTKD1 gene mutation with ALS like presentation: a case report.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {25}, number = {3-4}, pages = {413-415}, doi = {10.1080/21678421.2023.2273366}, pmid = {37880984}, issn = {2167-9223}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/genetics/metabolism ; Ketoglutarate Dehydrogenase Complex/genetics/metabolism ; *Ketone Oxidoreductases/genetics/metabolism ; Mitochondria ; Mutation/genetics ; Aged ; }, abstract = {DHTKD1 is a nuclear gene that encodes "dehydrogenase E1 and transketolase domain-containing 1", essential in mitochondrial metabolism. First identified in the patients of 2-amino-apidic and 2 oxoapidic aciduria, mutation in this gene has recently been implicated in CMT2Q and ALS. Here we report the case of a septuagenarian who presented with a 2 years progressive history of respiratory and neck muscle weakness without significant bulbar and limb involvement. Clinical and electrophysiological examination revealed lower motor neuron involvement with widespread chronic denervation and reinnervation. Clinical exome sequencing revealed a heterozygous nonsense variant in exon 8 of the DHTKD1 gene, which was previously described in CMT2Q. This report highlights the pleotropic phenotypic presentation of DHTKD1 mutation and the need for genetic testing even in sporadic cases of ALS presenting at a later age.}, } @article {pmid37880536, year = {2024}, author = {Iazzolino, B and Grassano, M and Moglia, C and Canosa, A and Manera, U and Vasta, R and Cabras, S and Callegaro, S and Matteoni, E and Di Pede, F and Palumbo, F and Mora, G and Calvo, A and Chiò, A}, title = {High serum uric acid levels are protective against cognitive impairment in amyotrophic lateral sclerosis.}, journal = {Journal of neurology}, volume = {271}, number = {2}, pages = {955-961}, pmid = {37880536}, issn = {1432-1459}, support = {RF-2016-02362405//Ministero della Salute/ ; 2017SNW5MB//Ministero dell'Istruzione, dell'Università e della Ricerca/ ; 259867//Seventh Framework Programme/ ; 101017598//Horizon 2020 Framework Programme/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/epidemiology ; *Frontotemporal Dementia/complications/diagnosis ; Uric Acid ; *Cognitive Dysfunction/diagnosis ; *Cognition Disorders/complications ; }, abstract = {BACKGROUND: Uric acid (UA) has emerged as a factor that can modify cognitive function both in the general population and in people with neurodegenerative disorders. Since very few data are available concerning amyotrophic lateral sclerosis (ALS), we explored the correlation of UA levels and cognitive impairment in a large cohort of ALS patients.

METHODS: We enrolled ALS patients consecutively seen at the Turin ALS expert center in the 2007-2018 period who underwent both cognitive/behavioral and UA evaluation at diagnosis. Patients were classified in 5 categories: normal cognition (ALS-CN), isolated cognitive impairment (ALSci), isolated behavioural impairment (ALSbi), cognitive and behavioural impairment (ALScbi), frontotemporal dementia (ALS-FTD). For this study, ALSci, ALSbi and ALScbi were merged as ALS with intermediate cognitive impairment (ALS-INT).

RESULTS: Out of the 841 ALS patients, 422 had ALS-CN, 271 ALS-INT and 148 ALS-FTD. The mean values of UA were significantly different among the cognitive subgroups of patients, with the lowest values in the ALS-FTD (ALS-CN, 288.5 ± 78.0 (μmol/L; ALS-INT, 289.7 ± 75.5 μmol/L; ALS-FTD, 271.8 ± 74.9 μmol/L; p = 0.046). The frequency of ALS-FTD was significantly higher in the 1st tertile of UA. Lower UA levels were independently associated with FTD (OR 1.32, 95% c.i. 1.01-1.43; p = 0.038) in binary logistic regression.

CONCLUSIONS: We found that in ALS lower UA serum levels are correlated with reduced frequency of co-morbid FTD. Patients with intermediate cognitive impairment showed UA levels similar to ALS-CN but higher than ALS-FTD, implying that higher UA levels can prevent or delay cognitive function deterioration.}, } @article {pmid37879951, year = {2023}, author = {Liu, JY and Lu, YR and Guo, J and Li, H and Wang, Y and Zhao, YQ and Li, J and Wang, Q}, title = {Effect of electroacupuncture intervention on the spinal cord PPIA/NF-κB signaling pathway in mice with amyotrophic lateral sclerosis.}, journal = {Zhen ci yan jiu = Acupuncture research}, volume = {48}, number = {10}, pages = {1009-1016}, doi = {10.13702/j.1000-0607.20230251}, pmid = {37879951}, issn = {1000-0607}, mesh = {Animals ; Mice ; *Amyotrophic Lateral Sclerosis/genetics/therapy/metabolism ; DNA-Binding Proteins/metabolism ; *Electroacupuncture ; Motor Neurons/metabolism ; NF-kappa B/genetics/metabolism ; Riluzole ; Signal Transduction ; Spinal Cord ; Superoxide Dismutase-1/genetics/metabolism ; Peptidylprolyl Isomerase/metabolism ; }, abstract = {OBJECTIVES: To observe the effects of electroacupuncture (EA) on motor function, expression of extracellular cyclophile A(PPIA) and PPIA/nuclear factor-κB (NF-κB) signaling pathway in spinal cord of amyotrophic la-teral sclerosis (ALS) mice, so as to explore the mechanism of EA intervention in regulating extracellular PPIA on neuroinflammation in ALS mice.

METHODS: Thirty ALS-SOD1[G93A] mice with hSOD1-G93A gene were randomly divided into model, EA and Riluzole groups , with 10 mice in each group, and other 10 ALS-SOD1[G93A] negative mice were used as the blank group. EA was applied to bilateral "Yanglingquan"(GB34) and "Zusanli"(ST36) for 20 min once daily, 5 days a week for 2 weeks. In the Riluzole group, riluzole solution (30 mg·kg[-1]·d[-1]) was administrated intragastrically, and the treatment time was the same as that in the EA group.Rotating rod experiment and open field experiment were used to evaluate the changes in motor function of mice .The morphology of motor neurons in the anterior horn of spinal cord was observed by HE staining.The relative protein expression levels of PPIA, TDP-43 and NF-κB in the spinal cord were detected by Western blot.The positive expression level of TDP-43 in the spinal cord was detected by immunohistochemistry. The positive expression level of PPIA in spinal cord was marked by immunofluorescence. Serum PPIA content was determined by ELISA.

RESULTS: Compared with the blank group, the time of rod dropping and the total distance of open field movement in the model group were shortened (P<0.01), the number of motor neurons in the anterior horn of the spinal cord was reduced, the cell morphology was incomplete, the cell body was atrophied, the protein expression and positive expression of TDP-43 were increased (P<0.01), the protein expressions of PPIA and NF-κB in the spinal cord were increased(P<0.01), the serum content of PPIA and immunofluorescence expression of PPIA in spinal cord were increased (P<0.01). Compared with the model group, the time of rod dropping and the total distance of open field movement of mice in the EA group and the Riluzole group were prolonged (P<0.05, P<0.01), and the injury of motor neuron in the anterior horn of the spinal cord was decreased, the protein expression and positive expression of TDP-43 in the spinal cord were decreased (P<0.05, P<0.01)；the relative expression levels of PPIA and NF-κB proteins were decreased (P<0.05, P<0.01), and the content of PPIA in serum and the immunofluorescence expression of PPIA in the spinal cord were decreased (P<0.05, P<0.01) in the EA group；the relative protein expression of NF-κB and fluorescence expression of PPIA in spinal cord of mice in the Riluzole group were decreased (P<0.05).

CONCLUSIONS: EA intervention can improve motor function in ALS mice, and its mechanism may be related to the inhibition of PPIA/NF-κB signaling pathway by EA to alleviating neuroinflammatory response.}, } @article {pmid37877583, year = {2024}, author = {Haldar, S and Khan, AH and De, A and Reichmayr, F and Morag, A and Yu, M and Schneemann, A and Kaskel, S}, title = {Fluorinated Benzimidazole-Linked Highly Conjugated Polymer Enabling Covalent Polysulfide Anchoring for Stable Sulfur Batteries.}, journal = {Chemistry (Weinheim an der Bergstrasse, Germany)}, volume = {30}, number = {2}, pages = {e202302779}, doi = {10.1002/chem.202302779}, pmid = {37877583}, issn = {1521-3765}, support = {SPP2248//Deutsche Forschungsgemeinschaft/ ; }, abstract = {Sulfur is one of the most abundant and economical elements in the p-block family and highly redox active, potentially utilizable as a charge-storing electrode with high theoretical capacities. However, its inherent good solubility in many electrolytes inhibits its accessibility as an electrode material in typical metal-sulfur batteries. In this work, the synthetically designed fluorinated porous polymer, when treated with elemental sulfur through a well-known nucleophilic aromatic substitution mechanism (SN Ar), allows for the covalent integration of polysulfides into a highly conjugated benzimidazole polymer by replacing the fluorine atoms. Chemically robust benzimidazole linkages allow such harsh post-synthetic treatment and facilitate the electronic activation of the anchored polysulfides for redox reactions under applied potential. The electrode amalgamated with sulfurized polymer mitigates the so-called polysulfide shuttle effect in the lithium-sulfur (Li-S) battery and also enables a reversible, more environmentally friendly, and more economical aluminum-sulfur (Al-S) battery that is configured with mostly p-block elements as cathode, anode, and electrolytes. The improved cycling stabilities and reduction of the overpotential in both cases pave the way for future sustainable energy storage solutions.}, } @article {pmid37877361, year = {2023}, author = {Heyming, TW and Knudsen-Robbins, C and Shelton, SK and Pham, PK and Brukman, S and Wickens, M and Valdez, B and Bacon, K and Thorpe, J and Kwon, KT and Schultz, C}, title = {9-1-1 Activations from Ambulatory Care Centers: A Sicker Pediatric Population.}, journal = {Prehospital and disaster medicine}, volume = {38}, number = {6}, pages = {749-756}, pmid = {37877361}, issn = {1945-1938}, mesh = {Child ; Child, Preschool ; Female ; Humans ; Male ; Ambulatory Care/statistics & numerical data ; *Emergency Medical Services/statistics & numerical data ; Emergency Service, Hospital ; Retrospective Studies ; Life Support Care/statistics & numerical data ; }, abstract = {BACKGROUND: Pediatric patients transferred by Emergency Medical Services (EMS) from urgent care (UC) and office-based physician practices to the emergency department (ED) following activation of the 9-1-1 EMS system are an under-studied population with scarce literature regarding outcomes for these children. The objectives of this study were to describe this population, explore EMS level-of-care transport decisions, and examine ED outcomes.

METHODS: This was a retrospective review of patients zero to <15 years of age transported by EMS from UC and office-based physician practices to the ED of two pediatric receiving centers from January 2017 through December 2019. Variables included reason for transfer, level of transport, EMS interventions and medications, ED medications/labs/imaging ordered in the first hour, ED procedures, ED disposition, and demographics. Data were analyzed with descriptive statistics, X test, point biserial correlation, two-sample z test, Mann-Whitney U test, and 2-way ANOVA.

RESULTS: A total of 450 EMS transports were included in this study: 382 Advanced Life Support (ALS) runs and 68 Basic Life Support (BLS) runs. The median patient age was 2.66 years, 60.9% were male, and 60.7% had private insurance. Overall, 48.9% of patients were transported from an office-based physician practice and 25.1% were transported from UC. Almost one-half (48.7%) of ALS patients received an EMS intervention or medication, as did 4.41% of BLS patients. Respiratory distress was the most common reason for transport (46.9%). Supplemental oxygen was the most common EMS intervention and albuterol was the most administered EMS medication. There was no significant association between level of transport and ED disposition (P = .23). The in-patient admission rate for transported patients was significantly higher than the general ED admission rate (P <.001).

CONCLUSION: This study demonstrates that pediatric patients transferred via EMS after activation of the 9-1-1 system from UC and medical offices are more acutely ill than the general pediatric ED population and are likely sicker than the general pediatric EMS population. Paramedics appear to be making appropriate level-of-care transport decisions.}, } @article {pmid37877320, year = {2024}, author = {Yom-Tov, E and Navar, I and Fraenkel, E and Berry, JD}, title = {Identifying amyotrophic lateral sclerosis through interactions with an internet search engine.}, journal = {Muscle & nerve}, volume = {69}, number = {1}, pages = {40-47}, doi = {10.1002/mus.27991}, pmid = {37877320}, issn = {1097-4598}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis ; Search Engine ; Delayed Diagnosis ; *Motor Neuron Disease ; *Cognitive Dysfunction ; }, abstract = {INTRODUCTION/AIMS: Amyotrophic lateral sclerosis (ALS), a motor neuron disease, remains a clinical diagnosis with an average time from onset of symptoms to diagnosis of about 1 year. Herein we examine the possibility that interactions with an internet search engine can identify people with ALS.

METHODS: We identified 285 anonymous Bing users whose queries indicated that they had been diagnosed with ALS and matched them to: (1) 3276 control users; and (2) 1814 users whose searches indicated they had ALS disease mimics. We tested whether the ALS group could be distinguished from controls and disease mimics based on search engine query data. Finally, we conducted a prospective validation from participants who provided access to their Bing search data.

RESULTS: The model distinguished between the ALS group and controls with an area under the curve (AUC) of 0.81. Model scores for the ALS group differed from the disease mimics group (rank sum test, p < .05 with Bonferroni correction). Mild cognitive impairment could not be distinguished from ALS (p > .05). In the prospective analysis, the model reached an AUC of 0.74.

DISCUSSION: Our results suggest that interactions with search engines should be further studied to understand the potential to act as a tool to assist in screening for ALS and to reduce diagnostic delay.}, } @article {pmid37877256, year = {2024}, author = {Gariscsak, PJ and Appireddy, R and Vyas, A and Ritsma, BR}, title = {Virtual Multidisciplinary ALS Clinic Care During the COVID-19 Pandemic: A Canadian Cohort.}, journal = {The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques}, volume = {51}, number = {5}, pages = {719-722}, doi = {10.1017/cjn.2023.302}, pmid = {37877256}, issn = {0317-1671}, } @article {pmid37877011, year = {2023}, author = {Ghaderi, S and Batouli, SAH and Mohammadi, S and Fatehi, F}, title = {Iron quantification in basal ganglia using quantitative susceptibility mapping in a patient with ALS: a case report and literature review.}, journal = {Frontiers in neuroscience}, volume = {17}, number = {}, pages = {1229082}, pmid = {37877011}, issn = {1662-4548}, abstract = {BACKGROUND: Quantitative susceptibility mapping (QSM) is a magnetic resonance imaging (MRI) technique that can measure the magnetic susceptibility of tissues, which can reflect their iron content. QSM has been used to detect iron accumulation in cortical and subcortical brain regions. However, its application in subcortical regions such as the basal ganglia, particularly the putamen, is rare in patients with amyotrophic lateral sclerosis (ALS).

We present the case of a 40-year-old male patient with ALS who underwent an MRI for QSM. We compared his QSM images with those of a control subject and performed a quantitative analysis of the magnetic susceptibility values in the putamen regions. We also reviewed the literature on previous QSM studies in ALS and summarized their methods and findings. Our QSM analysis revealed increased magnetic susceptibility values in the bilateral putamen of the ALS patient compared to controls, indicating iron overload. This finding is consistent with previous studies reporting iron dysregulation in subcortical nuclei in ALS. We also discussed the QSM processing techniques used in our study and in the literature, highlighting their advantages and limitations.

CONCLUSION: This case report demonstrates the potential of QSM as a sensitive MRI biomarker for evaluating iron levels in subcortical regions of ALS patients. QSM can provide quantitative information on iron deposition patterns in both motor and extra-motor areas of ALS patients, which may help understand the pathophysiology of ALS and monitor disease progression. Further studies with larger samples are needed to validate these results and explore the clinical implications of QSM in ALS.}, } @article {pmid37875807, year = {2023}, author = {Loubet, I and Meyer, L and Michel, S and Pernin, F and Carrère, S and Barrès, B and Le Corre, V and Délye, C}, title = {A high diversity of non-target site resistance mechanisms to acetolactate-synthase (ALS) inhibiting herbicides has evolved within and among field populations of common ragweed (Ambrosia artemisiifolia L.).}, journal = {BMC plant biology}, volume = {23}, number = {1}, pages = {510}, pmid = {37875807}, issn = {1471-2229}, support = {DRAGON 29001099-1944//Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement/ ; DRAGON 29001099-1944//ACTA - Les instituts techniques agricoles/ ; 2018-CRD-02 PPV18//Agence Nationale de Sécurité Sanitaire de l'Alimentation, de l'Environnement et du Travail/ ; 2018-CRD-02 PPV18//Agence Nationale de Sécurité Sanitaire de l'Alimentation, de l'Environnement et du Travail/ ; 2018-CRD-02 PPV18//Agence Nationale de Sécurité Sanitaire de l'Alimentation, de l'Environnement et du Travail/ ; 2018-CRD-02 PPV18//Agence Nationale de Sécurité Sanitaire de l'Alimentation, de l'Environnement et du Travail/ ; 2018-CRD-02 PPV18//Agence Nationale de Sécurité Sanitaire de l'Alimentation, de l'Environnement et du Travail/ ; 2018-CRD-02 PPV18//Agence Nationale de Sécurité Sanitaire de l'Alimentation, de l'Environnement et du Travail/ ; }, mesh = {Humans ; Ambrosia/genetics ; *Herbicides/pharmacology ; *Acetolactate Synthase ; Transcriptome ; Herbicide Resistance/genetics ; }, abstract = {BACKGROUND: Non-target site resistance (NTSR) to herbicides is a polygenic trait that threatens the chemical control of agricultural weeds. NTSR involves differential regulation of plant secondary metabolism pathways, but its precise genetic determinisms remain fairly unclear. Full-transcriptome sequencing had previously been implemented to identify NTSR genes. However, this approach had generally been applied to a single weed population, limiting our insight into the diversity of NTSR mechanisms. Here, we sought to explore the diversity of NTSR mechanisms in common ragweed (Ambrosia artemisiifolia L.) by investigating six field populations from different French regions where NTSR to acetolactate-synthase-inhibiting herbicides had evolved.

RESULTS: A de novo transcriptome assembly (51,242 contigs, 80.2% completeness) was generated as a reference to seek genes differentially expressed between sensitive and resistant plants from the six populations. Overall, 4,609 constitutively differentially expressed genes were identified, of which none were common to all populations, and only 197 were shared by several populations. Similarly, population-specific transcriptomic response was observed when investigating early herbicide response. Gene ontology enrichment analysis highlighted the involvement of stress response and regulatory pathways, before and after treatment. The expression of 121 candidate constitutive NTSR genes including CYP71, CYP72, CYP94, oxidoreductase, ABC transporters, gluco and glycosyltransferases was measured in 220 phenotyped plants. Differential expression was validated in at least one ragweed population for 28 candidate genes. We investigated whether expression patterns at some combinations of candidate genes could predict phenotype. Within populations, prediction accuracy decreased when applied to an additional, independent plant sampling. Overall, a wide variety of genes linked to NTSR was identified within and among ragweed populations, of which only a subset was captured in our experiments.

CONCLUSION: Our results highlight the complexity and the diversity of NTSR mechanisms that can evolve in a weed species in response to herbicide selective pressure. They strongly point to a non-redundant, population-specific evolution of NTSR to ALS inhibitors in ragweed. It also alerts on the potential of common ragweed for rapid adaptation to drastic environmental or human-driven selective pressures.}, } @article {pmid37875404, year = {2023}, author = {Luo, S and Angrick, M and Coogan, C and Candrea, DN and Wyse-Sookoo, K and Shah, S and Rabbani, Q and Milsap, GW and Weiss, AR and Anderson, WS and Tippett, DC and Maragakis, NJ and Clawson, LL and Vansteensel, MJ and Wester, BA and Tenore, FV and Hermansky, H and Fifer, MS and Ramsey, NF and Crone, NE}, title = {Stable Decoding from a Speech BCI Enables Control for an Individual with ALS without Recalibration for 3 Months.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {10}, number = {35}, pages = {e2304853}, pmid = {37875404}, issn = {2198-3844}, support = {U01 DC016686/DC/NIDCD NIH HHS/United States ; UH3 NS114439/NS/NINDS NIH HHS/United States ; U01DC016686/DC/NIDCD NIH HHS/United States ; UH3NS114439/NS/NINDS NIH HHS/United States ; }, mesh = {Humans ; Speech ; *Brain-Computer Interfaces ; *Amyotrophic Lateral Sclerosis/complications ; Electrocorticography ; }, abstract = {Brain-computer interfaces (BCIs) can be used to control assistive devices by patients with neurological disorders like amyotrophic lateral sclerosis (ALS) that limit speech and movement. For assistive control, it is desirable for BCI systems to be accurate and reliable, preferably with minimal setup time. In this study, a participant with severe dysarthria due to ALS operates computer applications with six intuitive speech commands via a chronic electrocorticographic (ECoG) implant over the ventral sensorimotor cortex. Speech commands are accurately detected and decoded (median accuracy: 90.59%) throughout a 3-month study period without model retraining or recalibration. Use of the BCI does not require exogenous timing cues, enabling the participant to issue self-paced commands at will. These results demonstrate that a chronically implanted ECoG-based speech BCI can reliably control assistive devices over long time periods with only initial model training and calibration, supporting the feasibility of unassisted home use.}, } @article {pmid37875101, year = {2024}, author = {Karacaoglu, C and Ersoy, S and Pala, E and Engin, VS}, title = {Evaluation of the Effectiveness of Wet Cupping Therapy in Fibromyalgia Patients: A Randomized Controlled Trial.}, journal = {Complementary medicine research}, volume = {31}, number = {1}, pages = {10-19}, doi = {10.1159/000534637}, pmid = {37875101}, issn = {2504-2106}, mesh = {Adult ; Female ; Humans ; Male ; Middle Aged ; *Cupping Therapy ; *Fibromyalgia/therapy ; Quality of Life ; Treatment Outcome ; Adolescent ; Young Adult ; Aged ; }, abstract = {INTRODUCTION: The aim of this study was to investigate the efficacy of wet cupping therapy (WCT) in patients diagnosed with fibromyalgia syndrome (FMS) as a complementary method in fibromyalgia treatment.

MATERIALS AND METHODS: A total of 120 participants between 18 and 65 years who were diagnosed with FMS were included in the study. They were randomized into two groups: 60 patients as the intervention and 60 patients as the control group. Each participant in the intervention group received 3 sessions of WCT once a month in addition to their ongoing treatment whereas the control group received only routine medical treatment. The evaluation was conducted in both groups based on the fibromyalgia impact questionnaire (FIQ), visual analog scale (VAS), and quality of life scale (QoL) parameters initially (at 0th week) and 1 week after the WCT sessions (at the 10th week). For the comparison of quantitative variables showing a normal distribution between the two groups, the Student's t test was used, while the Mann-Whitney U test was employed for variables not showing a normal distribution. The χ2 test and Continuity (Yates) Correction were used for the comparison of qualitative data. The significance level was set at p < 0.05.

RESULTS: The study included 107 female and 13 male participants, with a mean age of 45.79 ± 8.49 years. When comparing the pretreatment FIQ, VAS, and QoL scores with the scores obtained after three sessions of WCT, it was observed that in the WCT group, the FIQ and VAS values significantly decreased compared to the control group while the QoL significantly increased compared to the control group (p < 0.001 in all).

CONCLUSION: The findings obtained from this study indicate that WCT can be an effective treatment option for patients with FMS.

UNLABELLED: EinleitungMit dieser Studie soll die Wirksamkeit der blutigen Schröpftherapie (wet cupping therapy, WCT) bei Patienten mit diagnostiziertem Fibromyalgie-Syndrom (FMS) als komplementäre Methode in der Fibromyalgie-Behandlung untersucht werden.Material und MethodenInsgesamt wurden 120 Teilnehmer mit diagnostiziertem FMS zwischen 18 und 65 Jahren in die Studie aufgenommen. Diese wurden randomisiert zwei Gruppen zugeordnet: 60 Patienten wurden der Interventionsgruppe zugewiesen und 60 Patienten der Kontrollgruppe. Alle Teilnehmer der Interventionsgruppe erhielten einmal im Monat drei Sitzungen WCT zusätzlich zu ihrer laufenden Therapie, während die Kontrollgruppe lediglich die Standardbehandlung erhielt. Die Bewertung erfolgte in beiden Gruppen anhand des Fibromyalgia Impact Questionnaire (FIQ), der Visuellen Analogskala (VAS) und der Parameter der Quality of Life (QoL) Scale zu Beginn (in Woche 0) und eine Woche nach den WCT-Sitzungen (in Woche 10). Für den Vergleich von quantitativen Variablen, die eine Normalverteilung zwischen den beiden Gruppen aufwiesen, wurde der Student’s t-Test verwendet, während bei Variablen ohne Normalverteilung der Mann-Whitney-U-Test zur Anwendung kam. Qualitative Daten wurden mit dem Chi-Quadrat-Test und der Kontinuitätskorrektur (Yates) verglichen. Das Signifikanzniveau wurde auf p < 0,05 festgelegt.ErgebnisseIn die Studie wurden 107 Frauen und 13 Männer mit einem Durchschnittsalter von 45,79 ± 8,49 Jahren aufgenommen. Beim Vergleich der FIQ-, VAS- und QoL-Werte vor der Behandlung mit den nach drei WCT-Sitzungen erhobenen Werten zeigte sich in der WCT-Gruppe ein signifikanter Rückgang der FIQ- und VAS-Werte im Vergleich zur Kontrollgruppe, wohingegen bei der QoL ein signifikanter Anstieg gegenüber der Kontrollgruppe zu beobachten war (p < 0,001 in allen Fällen).SchlussfolgerungDie Ergebnisse dieser Studie deuten darauf hin, dass die WCT eine wirksame therapeutische Option für Patienten mit FMS sein kann.}, } @article {pmid37874905, year = {2023}, author = {Harrison, D and Billinton, A and Bock, MG and Doedens, JR and Gabel, CA and Holloway, MK and Porter, RA and Reader, V and Scanlon, J and Schooley, K and Watt, AP}, title = {Discovery of Clinical Candidate NT-0796, a Brain-Penetrant and Highly Potent NLRP3 Inflammasome Inhibitor for Neuroinflammatory Disorders.}, journal = {Journal of medicinal chemistry}, volume = {66}, number = {21}, pages = {14897-14911}, doi = {10.1021/acs.jmedchem.3c01398}, pmid = {37874905}, issn = {1520-4804}, mesh = {Humans ; *Inflammasomes/metabolism ; *NLR Family, Pyrin Domain-Containing 3 Protein/physiology ; Neuroinflammatory Diseases ; Brain/metabolism ; Esters ; }, abstract = {The NLRP3 inflammasome is a component of the innate immune system involved in the production of proinflammatory cytokines. Neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, multiple sclerosis, and amyotrophic lateral sclerosis, have been shown to have a component driven by NLRP3 inflammasome activation. Diseases such as these with large unmet medical needs have resulted in an interest in inhibiting the NLRP3 inflammasome as a potential pharmacological treatment, but to date, no marketed drugs specifically targeting NLRP3 have been approved. Furthermore, the requirement for CNS-penetrant molecules adds additional complexity to the search for NLRP3 inflammasome inhibitors suitable for clinical investigation of neuroinflammatory disorders. We designed a series of ester-substituted carbamate compounds as selective NLRP3 inflammasome inhibitors, leading to NT-0796, an isopropyl ester that undergoes intracellular conversion to NDT-19795, the carboxylic acid active species. NT-0796 was shown to be a potent and selective NLRP3 inflammasome inhibitor with demonstrated in vivo brain penetration.}, } @article {pmid37874476, year = {2024}, author = {Liu, Y and He, X and Yuan, Y and Li, B and Liu, Z and Li, W and Li, K and Tan, S and Zhu, Q and Tang, Z and Han, F and Wu, Z and Shen, L and Jiang, H and Tang, B and Qiu, J and Hu, Z and Wang, J}, title = {Association of TRMT2B gene variants with juvenile amyotrophic lateral sclerosis.}, journal = {Frontiers of medicine}, volume = {18}, number = {1}, pages = {68-80}, pmid = {37874476}, issn = {2095-0225}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics ; *Neurodegenerative Diseases ; HEK293 Cells ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive degeneration of motor neurons, and it demonstrates high clinical heterogeneity and complex genetic architecture. A variation within TRMT2B (c.1356G>T; p.K452N) was identified to be associated with ALS in a family comprising two patients with juvenile ALS (JALS). Two missense variations and one splicing variation were identified in 10 patients with ALS in a cohort with 910 patients with ALS, and three more variants were identified in a public ALS database including 3317 patients with ALS. A decreased number of mitochondria, swollen mitochondria, lower expression of ND1, decreased mitochondrial complex I activities, lower mitochondrial aerobic respiration, and a high level of ROS were observed functionally in patient-originated lymphoblastoid cell lines and TRMT2B interfering HEK293 cells. Further, TRMT2B variations overexpression cells also displayed decreased ND1. In conclusion, a novel JALS-associated gene called TRMT2B was identified, thus broadening the clinical and genetic spectrum of ALS.}, } @article {pmid37873269, year = {2023}, author = {Pottinger, TD and Motelow, JE and Povysil, G and Moreno, CAM and Ren, Z and Phatnani, H and , and Aitman, TJ and Santoyo-Lopez, J and , and Mitsumoto, H and , and , and , and Goldstein, DB and Harms, MB}, title = {Rare variant analyses validate known ALS genes in a multi-ethnic population and identifies ANTXR2 as a candidate in PLS.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, pmid = {37873269}, support = {K01 MH098126/MH/NIMH NIH HHS/United States ; RC2 MH089915/MH/NIMH NIH HHS/United States ; P01 HD080642/HD/NICHD NIH HHS/United States ; R01 MH097971/MH/NIMH NIH HHS/United States ; RC2 NS070344/NS/NINDS NIH HHS/United States ; UL1 TR000040/TR/NCATS NIH HHS/United States ; UL1 TR001873/TR/NCATS NIH HHS/United States ; UM1 AI100645/AI/NIAID NIH HHS/United States ; P30 AG028377/AG/NIA NIH HHS/United States ; U54 NS078059/NS/NINDS NIH HHS/United States ; P01 AG007232/AG/NIA NIH HHS/United States ; RF1 AG054023/AG/NIA NIH HHS/United States ; R01 HD048805/HD/NICHD NIH HHS/United States ; U01 HG007672/HG/NHGRI NIH HHS/United States ; U01 NS053998/NS/NINDS NIH HHS/United States ; U01 NS077303/NS/NINDS NIH HHS/United States ; U19 AI067854/AI/NIAID NIH HHS/United States ; R01 AG037212/AG/NIA NIH HHS/United States ; R01 ES016348/ES/NIEHS NIH HHS/United States ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease affecting over 30,000 people in the United States. It is characterized by the progressive decline of the nervous system that leads to the weakening of muscles which impacts physical function. Approximately, 15% of individuals diagnosed with ALS have a known genetic variant that contributes to their disease. As therapies that slow or prevent symptoms, such as antisense oligonucleotides, continue to develop, it is important to discover novel genes that could be targets for treatment. Additionally, as cohorts continue to grow, performing analyses in ALS subtypes, such as primary lateral sclerosis (PLS), becomes possible due to an increase in power. These analyses could highlight novel pathways in disease manifestation.

METHODS: Building on our previous discoveries using rare variant association analyses, we conducted rare variant burden testing on a substantially larger cohort of 6,970 ALS patients from a large multi-ethnic cohort as well as 166 PLS patients, and 22,524 controls. We used intolerant domain percentiles based on sub-region Residual Variation Intolerance Score (subRVIS) that have been described previously in conjunction with gene based collapsing approaches to conduct burden testing to identify genes that associate with ALS and PLS.

RESULTS: A gene based collapsing model showed significant associations with SOD1, TARDBP, and TBK1 (OR=19.18, p = 3.67 × 10[-39]; OR=4.73, p = 2 × 10[-10]; OR=2.3, p = 7.49 × 10[-9], respectively). These genes have been previously associated with ALS. Additionally, a significant novel control enriched gene, ALKBH3 (p = 4.88 × 10[-7]), was protective for ALS in this model. An intolerant domain based collapsing model showed a significant improvement in identifying regions in TARDBP that associated with ALS (OR=10.08, p = 3.62 × 10[-16]). Our PLS protein truncating variant collapsing analysis demonstrated significant case enrichment in ANTXR2 (p=8.38 × 10[-6]).

CONCLUSIONS: In a large multi-ethnic cohort of 6,970 ALS patients, rare variant burden testing validated known ALS genes and identified a novel potentially protective gene, ALKBH3. A first-ever analysis in 166 patients with PLS found a candidate association with loss-of-function mutations in ANTXR2.}, } @article {pmid37873158, year = {2024}, author = {Alecki, C and Rizwan, J and Le, P and Jacob-Tomas, S and Fernandez-Comaduran, M and Verbrugghe, M and Xu, JSM and Minotti, S and Lynch, J and Biswas, J and Wu, T and Durham, H and Yeo, GW and Vera, M}, title = {Localized synthesis of molecular chaperones sustains neuronal proteostasis.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2023.10.03.560761}, pmid = {37873158}, issn = {2692-8205}, support = {RF1 MH126719/MH/NIMH NIH HHS/United States ; U41 HG009889/HG/NHGRI NIH HHS/United States ; U24 HG009889/HG/NHGRI NIH HHS/United States ; R01 HG004659/HG/NHGRI NIH HHS/United States ; R01 HG011864/HG/NHGRI NIH HHS/United States ; R01 NS103172/NS/NINDS NIH HHS/United States ; }, abstract = {Neurons are challenged to maintain proteostasis in neuronal projections, particularly with the physiological stress at synapses to support intercellular communication underlying important functions such as memory and movement control. Proteostasis is maintained through regulated protein synthesis and degradation and chaperone-assisted protein folding. Using high-resolution fluorescent microscopy, we discovered that neurons localize a subset of chaperone mRNAs to their dendrites, particularly more proximal regions, and increase this asymmetric localization following proteotoxic stress through microtubule-based transport from the soma. The most abundant chaperone mRNA in dendrites encodes the constitutive heat shock protein 70, HSPA8. Proteotoxic stress in cultured neurons, induced by inhibiting proteasome activity or inducing oxidative stress, enhanced transport of Hspa8 mRNAs to dendrites and the percentage of mRNAs engaged in translation on mono and polyribosomes. Knocking down the ALS-related protein Fused in Sarcoma (FUS) and a dominant mutation in the heterogenous nuclear ribonucleoprotein A2/B1 (HNRNPA2B1) impaired stress-mediated localization of Hspa8 mRNA to dendrites in cultured murine motor neurons and human iPSC-derived neurons, respectively, revealing the importance of these RNA-binding proteins in maintaining proteostasis. These results reveal the increased dendritic localization and translation of the constitutive HSP70 Hspa8 mRNA as a crucial neuronal stress response to uphold proteostasis and prevent neurodegeneration.}, } @article {pmid37873064, year = {2023}, author = {Mann, N and Hill, J and Wang, K and Hughes, RM}, title = {OptoProfilin: A Single Component Biosensor of Applied Cellular Stress.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {37873064}, issn = {2692-8205}, support = {R15 NS125564/NS/NINDS NIH HHS/United States ; }, abstract = {The actin cytoskeleton is a biosensor of cellular stress and a potential prognosticator of human disease. In particular, aberrant cytoskeletal structures such as cofilin-actin rods and stress granules formed in response to energetic and oxidative stress are closely linked to neurodegenerative diseases such as Alzheimer's, Parkinson's, and ALS. Whether these cytoskeletal phenomena can be harnessed for the development of biosensors for cytoskeletal dysfunction and, by extension, neurodegenerative disease progression, remains an open question. In this work, we describe the design and development of an optogenetic iteration of profilin, an actin monomer binding protein with critical functions in cytoskeletal dynamics. We demonstrate that this optically activated profilin ('OptoProfilin') can act as an optically triggered biosensor of applied cellular stress in select immortalized cell lines. Notably, OptoProfilin is a single component biosensor, likely increasing its utility for experimentalists. While a large body of preexisting work closely links profilin activity with cellular stress and neurodegenerative disease, this, to our knowledge, is the first example of profilin as an optogenetic biosensor of stress-induced changes in the cytoskeleton.}, } @article {pmid37872794, year = {2023}, author = {You, FL and Xia, GF and Cai, J}, title = {Behavioural Variant Frontotemporal Dementia due to CCNF Gene Mutation: A Case Report.}, journal = {Current Alzheimer research}, volume = {20}, number = {5}, pages = {371-378}, doi = {10.2174/1567205020666230811092906}, pmid = {37872794}, issn = {1875-5828}, mesh = {Male ; Humans ; Aged ; *Frontotemporal Dementia/diagnosis/genetics ; *Amyotrophic Lateral Sclerosis/diagnosis/genetics ; *Neurodegenerative Diseases ; Memantine/therapeutic use ; Mutation/genetics ; Neuropsychological Tests ; Sodium ; Cyclins/genetics ; }, abstract = {BACKGROUND: Frontal, temporal lobe dementia (FTD) and amyotrophic lateral sclerosis (ALS) are fatal neurodegenerative diseases. Studies have found that CCNF mutations have been found in patients with familial and sporadic ALS and FTD. Behavioural variant frontotemporal dementia (bvFTD) is a clinical syndrome characterized by progressive deterioration of personality, social behaviour, and cognitive function, which is most closely related to genetic factors. As the early symptoms of bvFTD are highly heterogeneous, the condition is often misdiagnosed as Alzheimer's disease or psychiatric disorders. In this study, a bvFTD patient had a CCNF gene mutation, which led to ubiquitinated protein accumulation and ultimately caused neurodegenerative disease. Genetic detection should be improved urgently for bvFTD patients and family members to provide a clinical reference for early diagnosis of frontotemporal dementia.

CASE PRESENTATION: In this case, the patient was 65 years old with an insidious onset, early-onset memory loss, a significant decline in the episodic memory, an early AD diagnosis, and oral treatment with donepezil hydrochloride for 3 years with poor efficacy, followed by a change to oral memantine hydrochloride tablets, which controlled the condition for several months. His medication was switched to sodium oligomannate capsules, and his condition was gradually controlled, but no significant improvement was observed. After spontaneous drug withdrawal, the patient's condition progressed rapidly; therefore, he visited our hospital and underwent neuropsychological tests for moderate to severe cognitive impairment. AD cerebrospinal fluid markers showed no significant abnormalities, and cranial MRI revealed frontotemporal lobe atrophy and decreased hippocampal volume. Genetic testing for the presence of the CCNF gene revealed a c.1532C > A (p. T511N) heterozygous variant, which might be a diagnostic criterion for bvFTD. Therefore, the patient's symptoms recurred after transient improvement with the combination of donepezil, oral memantine hydrochloride tablets, and sodium oligomannate, but his overall condition was improved compared to that before, and this treatment regimen was continued to observe changes during the follow-up.

CONCLUSION: The early clinical manifestations of bvFTD are complex and variable, and the condition is easily misdiagnosed, thus delaying treatment. Therefore, for patients with a high clinical suspicion of FTD, in addition to a detailed understanding of their medical history and family history and improvement of relevant examinations, genetic testing should be performed as early as possible to help confirm the diagnosis. For diseases closely related to genes, genetic testing of other family members should be optimised as much as possible to allow early diagnosis and intervention and guide fertility in the next generation.}, } @article {pmid37872607, year = {2023}, author = {Falker-Gieske, C}, title = {Transcriptome driven discovery of novel candidate genes for human neurological disorders in the telomer-to-telomer genome assembly era.}, journal = {Human genomics}, volume = {17}, number = {1}, pages = {94}, pmid = {37872607}, issn = {1479-7364}, support = {R01 GM129325/GM/NIGMS NIH HHS/United States ; }, mesh = {Humans ; *Transcriptome/genetics ; Genomics ; *Nervous System Diseases/genetics ; Sequence Analysis, RNA ; Telomere ; }, abstract = {BACKGROUND: With the first complete draft of a human genome, the Telomere-to-Telomere Consortium unlocked previously concealed genomic regions for genetic analyses. These regions harbour nearly 2000 potential novel genes with unknown function. In order to uncover candidate genes associated with human neurological pathologies, a comparative transcriptome study using the T2T-CHM13 and the GRCh38 genome assemblies was conducted on previously published datasets for eight distinct human neurological disorders.

RESULTS: The analysis of differential expression in RNA sequencing data led to the identification of 336 novel candidate genes linked to human neurological disorders. Additionally, it was revealed that, on average, 3.6% of the differentially expressed genes detected with the GRCh38 assembly may represent potential false positives. Among the noteworthy findings, two novel genes were discovered, one encoding a pore-structured protein and the other a highly ordered β-strand-rich protein. These genes exhibited upregulation in multiple epilepsy datasets and hold promise as candidate genes potentially modulating the progression of the disease. Furthermore, an analysis of RNA derived from white matter lesions in multiple sclerosis patients indicated significant upregulation of 26 rRNA encoding genes. Additionally, putative pathology related genes were identified for Alzheimer's disease, amyotrophic lateral sclerosis, glioblastoma, glioma, and conditions resulting from the m.3242 A > G mtDNA mutation.

CONCLUSION: The results presented here underline the potential of the T2T-CHM13 assembly in facilitating the discovery of candidate genes from transcriptome data in the context of human disorders. Moreover, the results demonstrate the value of remapping sequencing data to a superior genome assembly. Numerous potential pathology related genes, either as causative factors or related elements, have been unveiled, warranting further experimental validation.}, } @article {pmid37872558, year = {2023}, author = {Schmitz, J and Liebold, F and Hinkelbein, J and Nöhl, S and Thal, SC and Sellmann, T}, title = {Cardiopulmonary resuscitation during hyperbaric oxygen therapy: a comprehensive review and recommendations for practice.}, journal = {Scandinavian journal of trauma, resuscitation and emergency medicine}, volume = {31}, number = {1}, pages = {57}, pmid = {37872558}, issn = {1757-7241}, mesh = {Humans ; *Cardiopulmonary Resuscitation ; *Heart Arrest/therapy ; Heart Massage ; *Hyperbaric Oxygenation ; Ventricular Fibrillation ; Practice Guidelines as Topic ; }, abstract = {BACKGROUND: Cardiopulmonary resuscitation (CPR) during hyperbaric oxygen therapy (HBOT) presents unique challenges due to limited access to patients in cardiac arrest (CA) and the distinct physiological conditions present during hyperbaric therapy. Despite these challenges, guidelines specifically addressing CPR during HBOT are lacking. This review aims to consolidate the available evidence and offer recommendations for clinical practice in this context.

MATERIALS AND METHODS: A comprehensive literature search was conducted in PubMed, EMBASE, Cochrane Library, and CINAHL using the search string: "(pressure chamber OR decompression OR hyperbaric) AND (cardiac arrest OR cardiopulmonary resuscitation OR advanced life support OR ALS OR life support OR chest compression OR ventricular fibrillation OR heart arrest OR heart massage OR resuscitation)". Additionally, relevant publications and book chapters not identified through this search were included.

RESULTS: The search yielded 10,223 publications, with 41 deemed relevant to the topic. Among these, 18 articles (primarily case reports) described CPR or defibrillation in 22 patients undergoing HBOT. The remaining 23 articles provided information or recommendations pertaining to CPR during HBOT. Given the unique physiological factors during HBOT, the limitations of current resuscitation guidelines are discussed.

CONCLUSIONS: CPR in the context of HBOT is a rare, yet critical event requiring special considerations. Existing guidelines should be adapted to address these unique circumstances and integrated into regular training for HBOT practitioners. This review serves as a valuable contribution to the literature on "CPR under special circumstances".}, } @article {pmid37872557, year = {2023}, author = {Li, C and Wei, Q and Hou, Y and Lin, J and Ou, R and Zhang, L and Jiang, Q and Xiao, Y and Liu, K and Chen, X and Yang, T and Song, W and Zhao, B and Wu, Y and Shang, H}, title = {Genome-wide analyses identify NEAT1 as genetic modifier of age at onset of amyotrophic lateral sclerosis.}, journal = {Molecular neurodegeneration}, volume = {18}, number = {1}, pages = {77}, pmid = {37872557}, issn = {1750-1326}, mesh = {Humans ; Age of Onset ; *Amyotrophic Lateral Sclerosis/genetics/metabolism ; Asian People ; Genome-Wide Association Study/methods ; Polymorphism, Single Nucleotide ; }, abstract = {BACKGROUND: Patients with amyotrophic lateral sclerosis (ALS) demonstrate great heterogeneity in the age at onset (AAO), which is closely related to the course of disease. However, most genetic studies focused on the risk of ALS, while the genetic background underlying AAO of ALS is still unknown.

METHODS: To identify genetic determinants influencing AAO of ALS, we performed genome-wide association analysis using a Cox proportional hazards model in 2,841 patients with ALS (Ndiscovery = 2,272, Nreplication = 569) in the Chinese population. We further conducted colocalization analysis using public cis-eQTL dataset, and Mendelian randomization analysis to identify risk factors for AAO of ALS. Finally, functional experiments including dual-luciferase reporter assay and RT-qPCR were performed to explore the regulatory effect of the target variant.

RESULTS: The total heritability of AAO of ALS was ~ 0.24. One novel locus rs10128627 (FRMD8) was significantly associated with earlier AAO by ~ 3.15 years (P = 1.54E-08, beta = 0.31, SE = 0.05). This locus was cis-eQTL of NEAT1 in multiple brain tissues and blood. Colocalization analysis detected association signals at this locus between AAO of ALS and expression of NEAT1. Furthermore, functional exploration supported the variant rs10128627 was associated with upregulated expression of NEAT1 in cell models and patients with ALS. Causal inference suggested higher total cholesterol, low-density lipoprotein, and eosinophil were nominally associated with earlier AAO of ALS, while monocyte might delay the AAO.

CONCLUSIONS: Collective evidence from genetic, bioinformatic, and functional results suggested NEAT1 as a key player in the disease progression of ALS. These findings improve the current understanding of the genetic role in AAO of ALS, and provide a novel target for further research on the pathogenesis and therapeutic options to delay the disease onset.}, } @article {pmid37871782, year = {2024}, author = {Burns, B and Marschner, I and Eggins, R and Buscher, H and Morton, RL and Bendall, J and Keech, A and Dennis, M and , }, title = {A randomized trial of expedited intra-arrest transfer versus more extended on-scene resuscitation for refractory out of hospital cardiac arrest: Rationale and design of the EVIDENCE trial.}, journal = {American heart journal}, volume = {267}, number = {}, pages = {22-32}, doi = {10.1016/j.ahj.2023.10.003}, pmid = {37871782}, issn = {1097-6744}, mesh = {Adolescent ; Adult ; Aged ; Humans ; Middle Aged ; Young Adult ; *Cardiopulmonary Resuscitation ; *Emergency Medical Services ; *Out-of-Hospital Cardiac Arrest/therapy ; Prospective Studies ; Quality of Life ; *Tachycardia, Ventricular ; }, abstract = {BACKGROUND: Refractory Out of Hospital Cardiac Arrest (r-OHCA) is common and the benefit versus harm of intra-arrest transport of patients to hospital is not clear.

OBJECTIVE: To assess the rate of survival to hospital discharge in adult patients with r-OHCA, initial rhythm pulseless ventricular tachycardia (VT)/ventricular fibrillation (VF) or Pulseless Electrical Activity (PEA) treated with 1 of 2 locally accepted standards of care:[1] expedited transport from scene; or[2] ongoing advanced life support (ALS) resuscitation on-scene.

HYPOTHESIS: We hypothesize that expedited transport from scene in r-OHCA improves survival with favorable neurological status/outcome.

METHODS/DESIGN: Phase III, multi-center, partially blinded, prospective, intention-to-treat, safety and efficacy clinical trial with contemporaneous registry of patient ineligible for the clinical trial. Eligible patients for inclusion are adults with witnessed r-OHCA; estimated age 18 to 70, assumed medical cause with immediate bystander cardiopulmonary resuscitation (CPR); initial rhythm of VF/pulseless VT, or PEA; no return of spontaneous circulation following 3 shocks and/or 15 minutes of professional on-scene resuscitation; with mechanical CPR available. Two hundred patients will be randomized in a 1:1 ratio to either expedited transport from scene or ongoing ALS at the scene of cardiac arrest.

SETTING: Two urban regions in NSW Australia.

OUTCOMES: Primary: survival to hospital discharge with cerebral performance category (CPC) 1 or 2. Secondary: safety, survival, prognostic factors, use of ECMO supported CPR and functional assessment at hospital discharge and 4 weeks and 6 months, quality of life, healthcare use and cost-effectiveness.

CONCLUSIONS: The EVIDENCE trial will determine the potential risks and benefits of an expedited transport from scene of cardiac arrest.}, } @article {pmid37870685, year = {2023}, author = {Zhou, L and Chen, W and Jiang, S and Xu, R}, title = {In Vitro Models of Amyotrophic Lateral Sclerosis.}, journal = {Cellular and molecular neurobiology}, volume = {43}, number = {8}, pages = {3783-3799}, pmid = {37870685}, issn = {1573-6830}, support = {30560042//National Natural Science Foundation of China/ ; 81160161//National Natural Science Foundation of China/ ; 81360198//National Natural Science Foundation of China/ ; 82160255//National Natural Science Foundation of China/ ; GJJ13198//Education Department of Jiangxi Province/ ; GJJ170021//Education Department of Jiangxi Province/ ; 20192BAB205043//Jiangxi Provincial Department of Science and Technology/ ; 20181019//Health and Family Planning Commission of Jiangxi Province/ ; 202210002//Health and Family Planning Commission of Jiangxi Province/ ; }, mesh = {Animals ; Humans ; Mice ; *Amyotrophic Lateral Sclerosis/metabolism ; Superoxide Dismutase-1/genetics/metabolism ; Disease Models, Animal ; Motor Neurons/metabolism ; Mutation/genetics ; Superoxide Dismutase/metabolism ; Mice, Transgenic ; }, abstract = {Amyotrophic Lateral Sclerosis (ALS) is one of the commonest neurodegenerative diseases of adult-onset, which is characterized by the progressive death of motor neurons in the cerebral cortex, brain stem and spinal cord. The dysfunction and death of motor neurons lead to the progressive muscle weakness, atrophy, fasciculations, spasticity and ultimately the whole paralysis of body. Despite the identification of several genetic mutations associated with the pathogenesis of ALS, including mutations in chromosome 9 open reading frame 72 leading to the abnormal expansion of GGGGCC repeat sequence, TAR DNA-binding protein 43, fused in sarcoma/translocated in liposarcoma, copper/zinc superoxide dismutase 1 (SOD1) and TANK-binding kinase 1, the exact mechanisms underlying the specific degeneration of motor neurons that causes ALS remain incompletely understood. At present, since the transgenic model expressed SOD1 mutants was established, multiple in vitro models of ALS have been developed for studying the pathology, pathophysiology and pathogenesis of ALS as well as searching the effective neurotherapeutics. This review reviewed the details of present established in vitro models used in studying the pathology, pathophysiology and pathogenesis of ALS. Meanwhile, we also discussed the advantages, disadvantages, cost and availability of each models.}, } @article {pmid37870677, year = {2024}, author = {Wang, S and Zheng, X and Wei, Q and Lin, J and Yang, T and Xiao, Y and Jiang, Q and Li, C and Shang, H}, title = {Rare DNAJC7 Variants May Play a Minor Role in Chinese Patients with ALS.}, journal = {Molecular neurobiology}, volume = {61}, number = {4}, pages = {2265-2269}, pmid = {37870677}, issn = {1559-1182}, support = {2022ZDZX0023//Sichuan Science and Technology Program/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics ; Genetic Association Studies ; Mutation, Missense ; Gene Frequency ; China ; Heat-Shock Proteins/genetics ; Molecular Chaperones ; }, abstract = {DnaJ heat shock protein family member C7 gene (DNAJC7) has been identified as a genetic risk factor for amyotrophic lateral sclerosis (ALS). In our study, we aimed to screen for rare variants in DNAJC7 in a large cohort of Chinese ALS patients, and investigate the genotype-phenotype correlation of DNAJC7 in ALS. Four (0.19%) variants of DNAJC7 with minor allele frequency (MAF) < 0.1% among 2124 patients were identified, including 1 protein-truncating variant and 3 missense variants, all of which were predicted to be damaging. The patients carrying variants of DNAJC7 in our cohort tented to have a limb onset and a relatively slow disease progression. However, burden analysis did not show an enrichment of rare damaging variants in ALS patients compared to controls. Further analysis involving diverse regions and larger sample size is necessary to elucidate the role of DNAJC7 in the pathogenicity of ALS.}, } @article {pmid37870566, year = {2023}, author = {Miller, CCJ and Gomez-Suaga, P}, title = {Poor communication between ER and mitochondria: a signature of ALS/FTD?.}, journal = {Aging}, volume = {15}, number = {20}, pages = {10814-10816}, pmid = {37870566}, issn = {1945-4589}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics ; *Frontotemporal Dementia/genetics ; DNA Repeat Expansion ; Mitochondria ; }, } @article {pmid37868386, year = {2023}, author = {Hoxhaj, P and Hastings, N and Kachhadia, MP and Gupta, R and Sindhu, U and Durve, SA and Azam, A and Auz Vinueza, MJ and Bhuvan, and Win, SH and Rathod, DC and Afsar, AP}, title = {Exploring Advancements in the Treatment of Amyotrophic Lateral Sclerosis: A Comprehensive Review of Current Modalities and Future Prospects.}, journal = {Cureus}, volume = {15}, number = {9}, pages = {e45489}, pmid = {37868386}, issn = {2168-8184}, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal and incurable disease requiring a multidisciplinary treatment approach and a collaborative therapeutic effort. A combination of both upper and lower motor neuron degeneration ultimately leads to respiratory failure, similar to other dementia-type neurodegenerative diseases. The aim of this paper is to pioneer current ALS research by carrying out a narrative literature review of the current treatment modalities of the disease. Through these efforts, we hope to condense the most pertinent information regarding current treatments and enhance the management of ALS patients as a whole, giving these patients a better quality of life as the search for a cure continues. We used a Pubmed search strategy and specific MeSH terms for the selection of the literature articles using the keywords "ALS," "new treatment," "treatment," and "symptomatic treatment." A combination of pharmaceutical interventions, psychological support, and physical rehabilitation has been most effective in enhancing the quality of life of patients with ALS (PALS). Among potential pharmacological therapies, only a few have been approved by the US Food and Drug Administration(FDA) to be used to treat ALS and its symptoms. Other treatment modalities being considered include gene therapy, cellular therapy, psychological therapy, physical therapy, and speech therapy, alongside robotics, alternative feeding methods, and communication devices.}, } @article {pmid37865869, year = {2024}, author = {Vélez-GóMEZ, B and Perna, A and Vazquez, C and Ketzoian, C and Lillo, P and Godoy-Reyes, G and Sáez, D and Zaldivar Vaillant, T and Gutiérrez Gil, JV and Lara-Fernández, GE and Povedano, M and Heverin, M and McFarlane, R and Logroscino, G and Hardiman, O}, title = {LAENALS: epidemiological and clinical features of amyotrophic lateral sclerosis in Latin America.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {25}, number = {1-2}, pages = {119-127}, doi = {10.1080/21678421.2023.2271517}, pmid = {37865869}, issn = {2167-9223}, mesh = {Male ; Humans ; Female ; Latin America/epidemiology ; *Amyotrophic Lateral Sclerosis/diagnosis/epidemiology ; Cuba/epidemiology ; Uruguay/epidemiology ; Prevalence ; }, abstract = {OBJECTIVE: The Latin American Epidemiologic study of ALS (LAENALS) aims to gather data on ALS epidemiology, phenotype, and risk factors in Cuba, Chile, and Uruguay, to understand the impact of genetic and environmental factors on ALS.

METHODS: A harmonized data collection protocol was generated, and a Latin-American Spanish language Register was constructed. Patient data were collected in Uruguay in 2018, in Chile from 2017 to 2019, and in Cuba between 2017 and 2018. Statistical analysis was performed using SPSS 25.0.0 software. Crude cumulative incidence, standardized incidence, and prevalence were calculated in the population aged 15 years and older.

RESULTS: During 2017-2019, 90 people with ALS from Uruguay (55.6% men), 219 from Chile (54.6% men), and 49 from Cuba (55.1% men) were included. The cumulative crude incidence in 2018 was 1.73/100,000 persons in Uruguay, 1.08 in Chile and 0.195 in Cuba. Crude prevalence in 2018 was 2.19 per 100,000 persons in Uruguay, 1.39 in Chile and 0.55 in Cuba. Mean age at onset was 61.8 ± 11.96 SD years in Uruguay, 61.9 ± 10.4 SD years in Chile, and 60.21 ± 12.45 SD years in Cuba (p = 0.75). Median survival from onset was 32.43 months (21.93 - 42.36) in Uruguay, 24 months (13.5 - 33.5) in Chile, and 29 months (15 - 42.5) in Cuba (p = 0.006).

CONCLUSIONS: These preliminary data from LAENALS confirm the lower incidence and prevalence of ALS in counties with admixed populations. The LAENALS database is now open to other Latin American countries for harmonized prospective data collection.}, } @article {pmid37865833, year = {2023}, author = {Wu, YK and Wecht, JM and Bloom, OE and Panza, GS and Harel, NY}, title = {Remote Ischemic conditioning as an emerging tool to improve corticospinal transmission in individuals with chronic spinal cord injury.}, journal = {Current opinion in neurology}, volume = {36}, number = {6}, pages = {523-530}, doi = {10.1097/WCO.0000000000001216}, pmid = {37865833}, issn = {1473-6551}, support = {R03 HD097709/HD/NICHD NIH HHS/United States ; }, mesh = {Adult ; Humans ; *Myocardial Infarction ; *Stroke ; *Spinal Cord Injuries ; Hypoxia ; }, abstract = {PURPOSE OF REVIEW: Remote ischemic conditioning (RIC) involves transient blood flow restriction to one limb leading to systemic tissue-protective effects. RIC shares some potential underlying mechanisms with intermittent hypoxia (IH), in which brief bouts of systemic hypoxia trigger increases in growth factor expression and neural plasticity. RIC has shown promise in acute myocardial infarction and stroke but may be applicable toward chronic neuropathology as well. Consequently, this review discusses similarities and differences between RIC and IH and presents preliminary and ongoing research findings regarding RIC.

RECENT FINDINGS: Several publications demonstrated that combining RIC with motor training may enhance motor learning in adults with intact nervous systems, though the precise mechanisms were unclear. Our own preliminary data has found that RIC, in conjunction with task specific exercise, can increase corticospinal excitability in a subset of people without neurological injury and in those with chronic cervical spinal cord injury or amyotrophic lateral sclerosis.

SUMMARY: RIC is a low-cost intervention easy to deliver in a clinical or home setting. Its potential application to facilitate neural plasticity and motor learning during rehabilitation training for individuals with chronic neurological disorders is a novel concept requiring further investigation to characterize mechanisms, safety, and efficacy.}, } @article {pmid37864389, year = {2024}, author = {Xiao, F and He, Z and Wang, S and Li, J and Fan, X and Yan, T and Yang, M and Yang, D}, title = {Regulatory mechanism of circular RNAs in neurodegenerative diseases.}, journal = {CNS neuroscience & therapeutics}, volume = {30}, number = {4}, pages = {e14499}, pmid = {37864389}, issn = {1755-5949}, support = {//China Scholarship Council/ ; //National Natural Science Foundation of China/ ; }, mesh = {Humans ; *Neurodegenerative Diseases/diagnosis/genetics ; RNA, Circular/metabolism ; *MicroRNAs/genetics ; *Alzheimer Disease/genetics ; *Parkinson Disease ; Biomarkers ; }, abstract = {BACKGROUND: Neurodegenerative disease is a collective term for a category of diseases that are caused by neuronal dysfunction, such as Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). Circular RNAs (circRNAs) are a class of non-coding RNAs without the 3' cap and 5' poly(A) and are linked by covalent bonds. CircRNAs are highly expressed in brain neurons and can regulate the pathological process of neurodegenerative diseases by affecting the levels of various deposition proteins.

AIMS: This review is aiming to suggest that the majority of circRNAs influence neurodegenerative pathologies mainly by affecting the abnormal deposition of proteins in neurodegenerative diseases.

METHODS: We systematically summarized the pathological features of neurodegenerative diseases and the regulatory mechanisms of circRNAs in various types of neurodegenerative diseases.

RESULTS: Neurodegenerative disease main features include intercellular ubiquitin-proteasome system abnormalities, changes in cytoskeletal proteins, and the continuous deposition of insoluble protein fragments and inclusion bodies in the cytoplasm or nucleus, resulting in impairment of the normal physiological processes of the neuronal system. CircRNAs have multiple mechanisms, such as acting as microRNA sponges, binding to proteins, and regulating transcription. CircRNAs, which are highly stable molecules, are expected to be potential biomarkers for the pathological detection of neurodegenerative diseases such as AD and PD.

CONCLUSIONS: In this review, we describe the regulatory roles and mechanisms of circRNAs in neurodegenerative diseases and aim to employ circRNAs as biomarkers for the diagnosis and treatment of neurodegenerative diseases.}, } @article {pmid37864255, year = {2023}, author = {Godfrey, RK and Alsop, E and Bjork, RT and Chauhan, BS and Ruvalcaba, HC and Antone, J and Gittings, LM and Michael, AF and Williams, C and Hala'ufia, G and Blythe, AD and Hall, M and Sattler, R and Van Keuren-Jensen, K and Zarnescu, DC}, title = {Modelling TDP-43 proteinopathy in Drosophila uncovers shared and neuron-specific targets across ALS and FTD relevant circuits.}, journal = {Acta neuropathologica communications}, volume = {11}, number = {1}, pages = {168}, pmid = {37864255}, issn = {2051-5960}, support = {RF1 NS091299/NS/NINDS NIH HHS/United States ; T34 GM008718/GM/NIGMS NIH HHS/United States ; R01 NS091299/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Humans ; *Amyotrophic Lateral Sclerosis/pathology ; DNA-Binding Proteins/genetics/metabolism ; Drosophila/metabolism ; *Frontotemporal Dementia/genetics/pathology ; Motor Neurons/metabolism ; *Pick Disease of the Brain/pathology ; RNA, Messenger ; *TDP-43 Proteinopathies/pathology ; }, abstract = {Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) comprise a spectrum of neurodegenerative diseases linked to TDP-43 proteinopathy, which at the cellular level, is characterized by loss of nuclear TDP-43 and accumulation of cytoplasmic TDP-43 inclusions that ultimately cause RNA processing defects including dysregulation of splicing, mRNA transport and translation. Complementing our previous work in motor neurons, here we report a novel model of TDP-43 proteinopathy based on overexpression of TDP-43 in a subset of Drosophila Kenyon cells of the mushroom body (MB), a circuit with structural characteristics reminiscent of vertebrate cortical networks. This model recapitulates several aspects of dementia-relevant pathological features including age-dependent neuronal loss, nuclear depletion and cytoplasmic accumulation of TDP-43, and behavioral deficits in working memory and sleep that occur prior to axonal degeneration. RNA immunoprecipitations identify several candidate mRNA targets of TDP-43 in MBs, some of which are unique to the MB circuit and others that are shared with motor neurons. Among the latter is the glypican Dally-like-protein (Dlp), which exhibits significant TDP-43 associated reduction in expression during aging. Using genetic interactions we show that overexpression of Dlp in MBs mitigates TDP-43 dependent working memory deficits, conistent with Dlp acting as a mediator of TDP-43 toxicity. Substantiating our findings in the fly model, we find that the expression of GPC6 mRNA, a human ortholog of dlp, is specifically altered in neurons exhibiting the molecular signature of TDP-43 pathology in FTD patient brains. These findings suggest that circuit-specific Drosophila models provide a platform for uncovering shared or disease-specific molecular mechanisms and vulnerabilities across the spectrum of TDP-43 proteinopathies.}, } @article {pmid37863900, year = {2023}, author = {Hutter, N and Hendricks, S and Jutila, A and Ricker, R and von Albedyll, L and Birnbaum, G and Haas, C}, title = {Digital elevation models of the sea-ice surface from airborne laser scanning during MOSAiC.}, journal = {Scientific data}, volume = {10}, number = {1}, pages = {729}, pmid = {37863900}, issn = {2052-4463}, support = {03F0866A//Bundesministerium für Bildung und Forschung (Federal Ministry of Education and Research)/ ; 03F0866A//Bundesministerium für Bildung und Forschung (Federal Ministry of Education and Research)/ ; NA20OAR4320271 - 2023-1311//United States Department of Commerce | National Oceanic and Atmospheric Administration (NOAA)/ ; }, abstract = {Airborne laser scanners (ALS) are used to map the sea-ice surface at sub-meter resolution. We conducted 64 flights over the Arctic sea ice between September 2019 and September 2020 during the Multidisciplinary drifting Observatory for the Study of Arctic Climate (MOSAiC) expedition to measure sea-ice surface elevation. The flights ranged from repeated, local-scale 5 × 5 km[2] floe grid surveys to regional-scale transects more than 100 km long. We provide data at different processing levels: geolocated elevation point clouds and gridded segments of elevation and freeboard with a spatial resolution of 0.5 m. The latter product is corrected for atmospheric backscatter, sea-ice drift, and offset in elevation due to degraded INS/GNSS solutions > 85° N. For floe grid surveys, all data are combined to merged two-dimensional elevation maps. Other provided parameters include laser reflectance and echo width. The presented data offer a unique possibility to study the temporal evolution, spatial distribution, and variability of the snow and sea-ice surface and their properties in addition to validating satellite products.}, } @article {pmid37863594, year = {2023}, author = {The Lancet Neurology, }, title = {Speeding up research to improve the lives of people with ALS.}, journal = {The Lancet. Neurology}, volume = {22}, number = {11}, pages = {971}, doi = {10.1016/S1474-4422(23)00380-0}, pmid = {37863594}, issn = {1474-4465}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy ; }, } @article {pmid37862967, year = {2023}, author = {Rabeh, N and Hajjar, B and Maraka, JO and Sammanasunathan, AF and Khan, M and Alkhaaldi, SMI and Mansour, S and Almheiri, RT and Hamdan, H and Abd-Elrahman, KS}, title = {Targeting mGluR group III for the treatment of neurodegenerative diseases.}, journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie}, volume = {168}, number = {}, pages = {115733}, doi = {10.1016/j.biopha.2023.115733}, pmid = {37862967}, issn = {1950-6007}, mesh = {Humans ; *Neurodegenerative Diseases/drug therapy ; Signal Transduction/physiology ; Glutamic Acid ; Neurotransmitter Agents ; Neurons ; *Receptors, Metabotropic Glutamate/physiology ; }, abstract = {Glutamate, an excitatory neurotransmitter, is essential for neuronal function, and it acts on ionotropic or metabotropic glutamate receptors (mGluRs). A disturbance in glutamatergic signaling is a hallmark of many neurodegenerative diseases. Developing disease-modifying treatments for neurodegenerative diseases targeting glutamate receptors is a promising avenue. The understudied group III mGluR 4, 6-8 are commonly found in the presynaptic membrane, and their activation inhibits glutamate release. Thus, targeted mGluRs therapies could aid in treating neurodegenerative diseases. This review describes group III mGluRs and their pharmacological ligands in the context of amyotrophic lateral sclerosis, Parkinson's, Alzheimer's, and Huntington's diseases. Attempts to evaluate the efficacy of these drugs in clinical trials are also discussed. Despite a growing list of group III mGluR-specific pharmacological ligands, research on the use of these drugs in neurodegenerative diseases is limited, except for Parkinson's disease. Future efforts should focus on delineating the contribution of group III mGluR to neurodegeneration and developing novel ligands with superior efficacy and a favorable side effect profile for the treatment of neurodegenerative diseases.}, } @article {pmid37862206, year = {2024}, author = {Hu, Y and Chen, W and Wei, C and Jiang, S and Li, S and Wang, X and Xu, R}, title = {Pathological mechanisms of amyotrophic lateral Sclerosis.}, journal = {Neural regeneration research}, volume = {19}, number = {5}, pages = {1036-1044}, pmid = {37862206}, issn = {1673-5374}, abstract = {Amyotrophic lateral sclerosis refers to a neurodegenerative disease involving the motor system, the cause of which remains unexplained despite several years of research. Thus, the journey to understanding or treating amyotrophic lateral sclerosis is still a long one. According to current research, amyotrophic lateral sclerosis is likely not due to a single factor but rather to a combination of mechanisms mediated by complex interactions between molecular and genetic pathways. The progression of the disease involves multiple cellular processes and the interaction between different complex mechanisms makes it difficult to identify the causative factors of amyotrophic lateral sclerosis. Here, we review the most common amyotrophic lateral sclerosis-associated pathogenic genes and the pathways involved in amyotrophic lateral sclerosis, as well as summarize currently proposed potential mechanisms responsible for amyotrophic lateral sclerosis disease and their evidence for involvement in amyotrophic lateral sclerosis. In addition, we discuss current emerging strategies for the treatment of amyotrophic lateral sclerosis. Studying the emergence of these new therapies may help to further our understanding of the pathogenic mechanisms of the disease.}, } @article {pmid37862205, year = {2024}, author = {Romano, R and Bucci, C}, title = {Antisense therapy: a potential breakthrough in the treatment of neurodegenerative diseases.}, journal = {Neural regeneration research}, volume = {19}, number = {5}, pages = {1027-1035}, pmid = {37862205}, issn = {1673-5374}, abstract = {Neurodegenerative diseases are a group of disorders characterized by the progressive degeneration of neurons in the central or peripheral nervous system. Currently, there is no cure for neurodegenerative diseases and this means a heavy burden for patients and the health system worldwide. Therefore, it is necessary to find new therapeutic approaches, and antisense therapies offer this possibility, having the great advantage of not modifying cellular genome and potentially being safer. Many preclinical and clinical studies aim to test the safety and effectiveness of antisense therapies in the treatment of neurodegenerative diseases. The objective of this review is to summarize the recent advances in the development of these new technologies to treat the most common neurodegenerative diseases, with a focus on those antisense therapies that have already received the approval of the U.S. Food and Drug Administration.}, } @article {pmid37862202, year = {2024}, author = {Tarot, P and Lasbleiz, C and Liévens, JC}, title = {NRF2 signaling cascade in amyotrophic lateral sclerosis: bridging the gap between promise and reality.}, journal = {Neural regeneration research}, volume = {19}, number = {5}, pages = {1006-1012}, pmid = {37862202}, issn = {1673-5374}, abstract = {Amyotrophic lateral sclerosis is a very disabling disease due to the degeneration of motor neurons. Symptoms include muscle weakness and atrophy, spasticity, and progressive paralysis. Currently, there is no treatment to reverse damage to motor neurons and cure amyotrophic lateral sclerosis. The only two treatments actually approved, riluzole and edaravone, have shown mitigated beneficial effects. The difficulty to find a cure lies in the complexity and multifaceted pattern of amyotrophic lateral sclerosis pathogenesis. Among mechanisms, abnormal RNA metabolism, nucleocytoplasmic transport defects, accumulation of unfolded protein, and mitochondrial dysfunction would in fine induce oxidative damage and vice versa. A potent therapeutic strategy will be to find molecules that break this vicious circle. Sharpening the nuclear factor erythroid-2 related factor 2 signaling may fulfill this objective since nuclear factor erythroid-2 related factor 2 has a multitarget profile controlling antioxidant defense, mitochondrial functioning, and inflammation. We here discuss the interest of developing nuclear factor erythroid-2 related factor 2-based therapy in regard to the pathophysiological mechanisms and we provide a general overview of the attempted clinical assays in amyotrophic lateral sclerosis.}, } @article {pmid37862201, year = {2024}, author = {Yang, K and Yan, Y and Yu, A and Zhang, R and Zhang, Y and Qiu, Z and Li, Z and Zhang, Q and Wu, S and Li, F}, title = {Mitophagy in neurodegenerative disease pathogenesis.}, journal = {Neural regeneration research}, volume = {19}, number = {5}, pages = {998-1005}, pmid = {37862201}, issn = {1673-5374}, abstract = {Mitochondria are critical cellular energy resources and are central to the life of the neuron. Mitophagy selectively clears damaged or dysfunctional mitochondria through autophagic machinery to maintain mitochondrial quality control and homeostasis. Mature neurons are postmitotic and consume substantial energy, thus require highly efficient mitophagy pathways to turn over damaged or dysfunctional mitochondria. Recent evidence indicates that mitophagy is pivotal to the pathogenesis of neurological diseases. However, more work is needed to study mitophagy pathway components as potential therapeutic targets. In this review, we briefly discuss the characteristics of nonselective autophagy and selective autophagy, including ERphagy, aggrephagy, and mitophagy. We then introduce the mechanisms of Parkin-dependent and Parkin-independent mitophagy pathways under physiological conditions. Next, we summarize the diverse repertoire of mitochondrial membrane receptors and phospholipids that mediate mitophagy. Importantly, we review the critical role of mitophagy in the pathogenesis of neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. Last, we discuss recent studies considering mitophagy as a potential therapeutic target for treating neurodegenerative diseases. Together, our review may provide novel views to better understand the roles of mitophagy in neurodegenerative disease pathogenesis.}, } @article {pmid37861203, year = {2024}, author = {Van Wijk, IF and Van Eijk, RPA and Van Boxmeer, L and Westeneng, HJ and Van Es, MA and Van Rheenen, W and Van Den Berg, LH and Eijkemans, MJC and Veldink, JH}, title = {Assessment of risk of ALS conferred by the GGGGCC hexanucleotide repeat expansion in C9orf72 among first-degree relatives of patients with ALS carrying the repeat expansion.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {25}, number = {1-2}, pages = {188-196}, doi = {10.1080/21678421.2023.2272187}, pmid = {37861203}, issn = {2167-9223}, mesh = {Humans ; Aged, 80 and over ; *Frontotemporal Dementia/genetics ; *Amyotrophic Lateral Sclerosis/epidemiology/genetics ; C9orf72 Protein/genetics ; DNA Repeat Expansion/genetics ; Proteins/genetics ; }, abstract = {OBJECTIVES: We aimed to estimate the age-related risk of ALS in first-degree relatives of patients with ALS carrying the C9orf72 repeat expansion.

METHODS: We included all patients with ALS carrying a C9orf72 repeat expansion in The Netherlands. Using structured questionnaires, we determined the number of first-degree relatives, their age at death due to ALS or another cause, or age at time of questionnaire. The cumulative incidence of ALS among first-degree relatives was estimated, while accounting for death from other causes. Variability in ALS risk between families was evaluated using a random effects hazards model. We used a second, distinct approach to estimate the risk of ALS and FTD in the general population, using previously published data.

RESULTS: In total, 214 of the 2,486 (9.2%) patients with ALS carried the C9orf72 repeat expansion. The mean risk of ALS at age 80 for first-degree relatives carrying the repeat expansion was 24.1%, but ranged between individual families from 16.0 to 60.6%. Using the second approach, we found the risk of ALS and FTD combined was 28.7% (95% CI 17.8%-54.3%) for carriers in the general population.

CONCLUSIONS: On average, our estimated risk of ALS in the C9orf72 repeat expansion was lower compared to historical estimates. We showed, however, that the risk of ALS likely varies between families and one overall penetrance estimate may not be sufficient to describe ALS risk. This warrants a tailor-made, patient-specific approach in testing. Further studies are needed to assess the risk of FTD in the C9orf72 repeat expansion.}, } @article {pmid37860934, year = {2024}, author = {Recasens, BB and Balañá Corberó, A and Llorens, JMM and Guillen-Sola, A and Moreno, MV and Escobar, GG and Umayahara, Y and Soh, Z and Tsuji, T and Rubio, MÁ}, title = {Sound-based cough peak flow estimation in patients with neuromuscular disorders.}, journal = {Muscle & nerve}, volume = {69}, number = {2}, pages = {213-217}, doi = {10.1002/mus.27987}, pmid = {37860934}, issn = {1097-4598}, mesh = {Humans ; Reproducibility of Results ; *Neuromuscular Diseases/complications ; Peak Expiratory Flow Rate ; *Nervous System Diseases ; Cough ; }, abstract = {INTRODUCTION/AIMS: Cough impairment is common in individuals with neuromuscular disorders and is associated with respiratory infections and shorter survival. Cough strength is assessed by measuring cough peak flow (CPF) using a flow meter, but this method requires a complex device setup and trained staff. The aim of the study is to evaluate the reliability of a smartphone app to estimate CPF based on cough sounds in a cohort of individuals with neuromuscular disorders.

METHODS: Individuals with neuromuscular disorders underwent CPF measurement with a flow meter and a smartphone app. A CPF <270 L/min was considered abnormal.

RESULTS: Of the 50 patients studied, 26 had amyotrophic lateral sclerosis (52%), 15 had hereditary myopathies (30%), and 9 had myasthenia gravis (18%). The intraclass correlation coefficient (ICC) between the CPF measured with a flow meter and CPF estimated with cough sounds was 0.774 (p < .001) even if the patients had orofacial weakness (ICC = 0.806, p < .001). The smartphone app had 94.4% sensitivity and 100% specificity to detect patients with CPF of less than 270 L/min.

DISCUSSION: Our findings suggest that sounds measured with a smartphone app provide a reliable estimate of CPF in patients with neuromuscular disorders, even in the presence of with orofacial weakness. This may be a convenient way to monitor respiratory involvement in patients with neuromuscular disorders, but larger studies of more diverse patient cohorts are needed.}, } @article {pmid37860271, year = {2023}, author = {Ayoubi, R and Alshafie, W and You, Z and Southern, K and McPherson, PS and Laflamme, C}, title = {Identification of high-performing antibodies for Superoxide dismutase [Cu-Zn] 1 (SOD1) for use in Western blot, immunoprecipitation, and immunofluorescence.}, journal = {F1000Research}, volume = {12}, number = {}, pages = {391}, pmid = {37860271}, issn = {2046-1402}, support = {FDN154305//CIHR/Canada ; }, mesh = {Humans ; *Superoxide Dismutase-1/immunology/genetics ; *Fluorescent Antibody Technique/methods ; *Immunoprecipitation/methods ; *Blotting, Western/methods ; *Antibodies/immunology ; Animals ; Mice ; }, abstract = {Superoxide dismutase [Cu-Zn] 1 (SOD1), is an antioxidant enzyme encoded by the gene SOD1, responsible for regulating oxidative stress levels by sequestering free radicals. Identified as the first gene with mutations in Amyotrophic lateral sclerosis (ALS), SOD1 is a determinant for studying diseases of aging and neurodegeneration. With guidance on well-characterized anti-SOD1 antibodies, the reproducibility of SOD1 research would be enhanced. In this study, we characterized eleven SOD1 commercial antibodies for Western blot, immunoprecipitation, and immunofluorescence using a standardized experimental protocol based on comparing read-outs in knockout cell lines and isogenic parental controls. We identified many high-performing antibodies and encourage readers to use this report as a guide to select the most appropriate antibody for their specific needs.}, } @article {pmid37859765, year = {2023}, author = {Vinceti, G and Carbone, C and Gallingani, C and Fiondella, L and Salemme, S and Zucchi, E and Martinelli, I and Gianferrari, G and Tondelli, M and Mandrioli, J and Chiari, A and Zamboni, G}, title = {The association between lifelong personality and clinical phenotype in the FTD-ALS spectrum.}, journal = {Frontiers in neuroscience}, volume = {17}, number = {}, pages = {1248622}, pmid = {37859765}, issn = {1662-4548}, abstract = {INTRODUCTION: Frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) are two phenotypes of the same neurodegenerative disease, the FTD-ALS spectrum. What determines the development of one rather than the other phenotype is still unknown. Based on the clinical observation that patients' personality seems to differ between the two phenotypes, i.e., ALS patients tend to display kind, prosocial behaviors whereas FTD patients tend to present anti-social behaviors, and that these traits are often reported as pre-existing the disease onset by caregivers, we set up to study experimentally patients' personality in their premorbid life.

METHODS: We first tested for differences between groups, then tested the association between premorbid personality and current functional organization of the brain. Premorbid personality of a cohort of forty patients, 27 FTD and 13 ALS, was explored through the NEO Personality Inventory 3 (NEO-PI-3), which analyses the five main personality factors, completed by the caregiver with reference to patient's personality 20 years before symptoms onset (premorbid). A subgroup of patients underwent a brain MRI including structural and resting-state functional MRI (rsfMRI).

RESULTS: A significant difference between FTD and ALS in premorbid personality emerged in the Openness (133.92 FTD vs. 149.84 ALS, p = 0.01) and Extraversion (136.55 FTD vs. 150.53 ALS, p = 0.04) factors. This suggests that ALS patients had been, in their premorbid life, more open to new experiences, more sociable and optimistic than FTD patients. They also showed greater functional connectivity than both FTD and a control group in the Salience resting state network, over and above differences in gray matter atrophy. Finally, there was a positive correlation between premorbid Openness and functional connectivity in the Salience network across all patients, suggesting a possible association between premorbid personality and current functional organization of the brain, irrespective of the degree of atrophy.

DISCUSSION: Our proof-of-concept results suggest that premorbid personality may eventually predispose to the development of one, rather than the other, phenotype in the FTD-ALS spectrum.}, } @article {pmid37858681, year = {2023}, author = {Wang, Y and Liang, W and Wang, T and Zhang, C and Yang, Y and Cong, C and Wang, X and Wang, S and Wang, D and Huo, D and Wang, H and Su, X and Tan, X and Feng, H}, title = {Researches of calcium-activated chloride channel ANO1 intervening amyotrophic lateral sclerosis progression by activating EGFR and CaMKII signaling.}, journal = {Brain research bulletin}, volume = {204}, number = {}, pages = {110792}, doi = {10.1016/j.brainresbull.2023.110792}, pmid = {37858681}, issn = {1873-2747}, mesh = {Animals ; Mice ; *Amyotrophic Lateral Sclerosis/metabolism ; Anoctamin-1 ; Calcium-Calmodulin-Dependent Protein Kinase Type 2/metabolism ; Chloride Channels ; Disease Models, Animal ; ErbB Receptors/metabolism ; Mice, Transgenic ; Superoxide Dismutase/metabolism ; Superoxide Dismutase-1/metabolism ; }, abstract = {BACKGROUND: ANO1 is closely correlated with the activation of EGFR and CaMKII, while EGFR and CaMKII show low activation in amyotrophic lateral sclerosis (ALS) models. Therefore, we designed experiments to verify that ANO1 may play a protective role on motor neurons in ALS by activating EGFR and CaMKII.

METHODS: The expression changes of ANO1, EGFR, CaMKII, pEGFR, and pCaMKII, cell survival status, and apoptosis were studied by western blot, real-time quantitative PCR, immunofluorescence, immunohistochemistry, CCK-8, and flow cytometry. The role of ANO1 in the ALS model by activating EGFR and CaMKII was studied by applying corresponding activators, inhibitors, gene silencing, and overexpression.

RESULTS: In hSOD1[G93A] transgenic animals and cell lines, low expression of ANO1 and low activation of EGFR and CaMKII were identified. ANO1 expression decreased gradually with the progression of ALS. Overexpression of ANO1 in the hSOD1[G93A] cell line and primary neurons of hSOD1[G93A] transgenic mice increased cell viability and decreased cell apoptosis. After the application of ANO1 inhibitor CaCC-inhA01 in hSOD1[G93A] cell line and primary neurons of hSOD1[G93A] transgenic mice, EGFR activator EGF and CaMKII activator Carbachol, increased cell viability and reduced cell apoptosis. After ANO1 was overexpressed in the hSOD1[G93A] cell line and primary neurons of hSOD1[G93A] transgenic mice, EGFR inhibitor AEE788 and CaMKII inhibitor KN93 decreased cell viability and increased cell apoptosis.

CONCLUSIONS: Our results suggest that ANO1 plays an important role in the survival of ALS motor neurons. ANO1 can increase cell activity and reduce apoptosis by activating EGFR and CaMKII signals.}, } @article {pmid37858624, year = {2024}, author = {Lauck, KC and Malick, H and Tolkachjov, SN}, title = {Response to Joshi et al's "Considerations for perioperative antibiotic prophylaxis in Mohs micrographic surgery".}, journal = {Journal of the American Academy of Dermatology}, volume = {90}, number = {3}, pages = {e103-e104}, doi = {10.1016/j.jaad.2023.10.019}, pmid = {37858624}, issn = {1097-6787}, mesh = {Humans ; *Mohs Surgery/adverse effects ; Antibiotic Prophylaxis ; *Skin Neoplasms/surgery ; Surgical Wound Infection/prevention & control ; }, } @article {pmid37858563, year = {2023}, author = {Ezenarro, J and García-Pizarro, Á and Busto, O and de Juan, A and Boqué, R}, title = {Analysing olive ripening with digital image RGB histograms.}, journal = {Analytica chimica acta}, volume = {1280}, number = {}, pages = {341884}, doi = {10.1016/j.aca.2023.341884}, pmid = {37858563}, issn = {1873-4324}, mesh = {*Olea/chemistry ; Olive Oil/analysis ; Fruit/chemistry ; }, abstract = {Digital images are commonly used to monitor processes that are based on colour changes due to their simplicity and easy capture. Colour information in these images can be analysed objectively and accurately using colour histograms. One such process is olive ripening, which is characterized by changes in chemical composition, sensory properties and can be followed by changes in physical appearance, mainly colour. The reference method to quantify the ripeness of olives is the Maturity Index (MI), which is determined by trained experts assigning individual olives into a colour scale through visual inspection. Instead, this study proposes a methodology based on Chemometrics Assisted Colour Histogram-based Analytical Systems (CACHAS) to automatically assess the MI of olives based on R, G, and B colour histograms derived from digital images. The methodology was shown to be easily transferable for routine analysis and capable of controlling the ripening of olives. The study also confirms the high potential of digital images to understand the ripening process of olives (and potentially other fruits) and to predict the MI with satisfactory accuracy, providing an objective and reproducible alternative to visual inspection of trained experts.}, } @article {pmid37858176, year = {2023}, author = {Xie, M and Pallegar, PN and Parusel, S and Nguyen, AT and Wu, LJ}, title = {Regulation of cortical hyperexcitability in amyotrophic lateral sclerosis: focusing on glial mechanisms.}, journal = {Molecular neurodegeneration}, volume = {18}, number = {1}, pages = {75}, pmid = {37858176}, issn = {1750-1326}, support = {R35 NS132326/NS/NINDS NIH HHS/United States ; RF1AG082314/AG/NIA NIH HHS/United States ; RF1 AG082314/AG/NIA NIH HHS/United States ; U19AG 069701/AG/NIA NIH HHS/United States ; R35NS132326/NS/NINDS NIH HHS/United States ; U19 AG069701/AG/NIA NIH HHS/United States ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/pathology ; Motor Neurons/pathology ; Neuroglia/pathology ; Microglia/pathology ; Disease Progression ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder characterized by the loss of both upper and lower motor neurons, resulting in muscle weakness, atrophy, paralysis, and eventually death. Motor cortical hyperexcitability is a common phenomenon observed at the presymptomatic stage of ALS. Both cell-autonomous (the intrinsic properties of motor neurons) and non-cell-autonomous mechanisms (cells other than motor neurons) are believed to contribute to cortical hyperexcitability. Decoding the pathological relevance of these dynamic changes in motor neurons and glial cells has remained a major challenge. This review summarizes the evidence of cortical hyperexcitability from both clinical and preclinical research, as well as the underlying mechanisms. We discuss the potential role of glial cells, particularly microglia, in regulating abnormal neuronal activity during the disease progression. Identifying early changes such as neuronal hyperexcitability in the motor system may provide new insights for earlier diagnosis of ALS and reveal novel targets to halt the disease progression.}, } @article {pmid37857264, year = {2024}, author = {Kiene, H and Hamre, HJ}, title = {A Fundamental Question for Complementary Medicine: Are There Other Forces in the Natural World Besides the Physical Forces?.}, journal = {Complementary medicine research}, volume = {31}, number = {1}, pages = {71-77}, doi = {10.1159/000534592}, pmid = {37857264}, issn = {2504-2106}, mesh = {*Complementary Therapies ; *Homeopathy ; DNA ; RNA ; }, abstract = {BACKGROUND: The integration of conventional and complementary medicine reflects the pluralism in science. Still, a critical issue is the conception of the natural world. Many complementary therapy systems seem to contradict the reductionist-atomistic paradigm that all of natural reality is essentially based on the physical interactions of atoms and molecules. Thus, a fundamental question about the natural world is: Do other than the physical forces exist?

SUMMARY: The assumption that no other than physical forces exist and work in the natural world is not tenable. For example, the formation and maintenance of the functional Gestalt of organisms cannot possibly be explained by molecular processes (e.g., from DNA to RNA and further to amino acids and proteins). The processes on each structural level - from molecules, organelles, cells, organs up to the whole organism - are regulated in regard to the formation of the next higher level. Specific Gestalt-forming forces exist and can be systematically investigated. Their existence implies an extended conception of matter. The Gestalt-forming forces and the extended concept of matter may be relevant for the scientific assessment of complementary therapies.

KEY MESSAGES: (i) In the natural world, specific Gestalt-forming forces exist in addition to the physical forces, and can be systematically investigated. (ii) The existence of these forces implies an extended conception of matter. (iii) These forces and this extended concept of matter may be relevant for the scientific assessment of complementary therapies, e.g., homeopathy.

UNLABELLED: HintergrundIn der Integration von konventioneller und komplementärer Medizin spiegelt sich der Methodenpluralismus der Wissenschaft. Die Ontologien vieler komplementärmedizinisches Systeme liegen allerdings außerhalb der Erklärbarkeit durch die Kräfte der Physik. Eine zentrale Frage ist deshalb: Gibt es Kräfte in der Natur, die eine materielle Wirkung haben, deren Ursprung aber nicht in Atomen oder Molekülen und in diesem Sinne nicht in der Materie liegt?ZusammenfassungDie Annahme, dass in der Natur keine anderen als die mit Atomen und Molekülen assoziierten physikalischen Kräfte existent und wirksam seien, ist wissenschaftlich nicht begründet. Beispielsweise ist die Bildung und Erhaltung der funktionsfähigen Gestalt von Organismen nicht durch molekulare Prozesse (z.B. von der DNA zur RNA und weiter zu Aminosäuren und Proteinen) erklärbar. Die Prozesse auf jeder strukturellen Ebene – von den Molekülen, Organellen, Zellen, Organen bis hinauf zum Gesamtorganismus – sind in Hinblick auf die Bildung der funktionsfähigen Gestalt der jeweils nächsthöheren Ebene gesteuert. Für diese Gestaltbildung gibt es spezifische Kräfte, die systematisch erforscht werden können. Ihre Existenz impliziert eine erweiterte Konzeption von Materie. Diese Gestalt-bildenden Kräfte und dieses erweiterte Konzept von Materie sind relevant für die wissenschaftliche Erfassung komplementärmedizinischer Systeme.Zentrale Aussagen(i) In der Natur sind außer den physikalischen Kräften noch weitere spezifische Kräfte wirksam, beispielsweise bei der Bildung und Erhaltung der funktionsfähigen Gestalt von Organismen. Diese Kräfte können systematisch erforscht werden. (ii) Die Existenz dieser Kräfte impliziert eine erweitere Konzeption von Materie. (iii) Diese Kräfte und das erweiterte Materiekonzept sind relevant für die wissenschaftliche Erfassung komplementärmedizinischer Systeme, beispielsweise der Homöopathie.}, } @article {pmid37856900, year = {2023}, author = {Magrì, B and D'Amico, AG and Maugeri, G and Morello, G and La Cognata, V and Saccone, S and Federico, C and Cavallaro, S and D'Agata, V}, title = {Neuroprotective effect of the PACAP-ADNP axis on SOD1G93A mutant motor neuron death induced by trophic factors deprivation.}, journal = {Neuropeptides}, volume = {102}, number = {}, pages = {102386}, doi = {10.1016/j.npep.2023.102386}, pmid = {37856900}, issn = {1532-2785}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology ; Pituitary Adenylate Cyclase-Activating Polypeptide/pharmacology/metabolism ; *Neuroprotective Agents/pharmacology/metabolism ; Superoxide Dismutase-1/genetics/metabolism/pharmacology ; Reactive Oxygen Species/metabolism ; *Neurodegenerative Diseases ; Motor Neurons/metabolism/pathology ; Superoxide Dismutase/genetics/metabolism ; Nerve Degeneration/metabolism/pathology ; Mutation ; Nerve Tissue Proteins/metabolism ; Homeodomain Proteins/genetics/metabolism/pharmacology ; }, abstract = {Amyotrophic lateral Sclerosis (ALS) is a neurodegenerative disease characterized by progressive degeneration of motor neurons in the central nervous system. Mutations in the gene encoding Cu/Zn superoxide dismutase (SOD1) account for approximately in 20% of familial ALS cases. The pathological mechanisms underlying the toxicity induced by mutated SOD1 are still unknown. However, it has been hypothesized that oxidative stress (OS) has a crucial role in motor neuron degeneration in ALS patients. Moreover, it has been described that SOD1 mutation interferes expression of nuclear factor erythroid 2-related factor 2 (Nrf2), a protective key modulator against OS and reactive oxygen species (ROS) formation. The protective effect of pituitary adenylate cyclase-activating peptide (PACAP) has been demonstrated in various neurological disorders, including ALS. Some of its effects are mediated by the stimulation of an intracellular factor known as activity-dependent protein (ADNP). The role of PACAP-ADNP axis on mutated SOD1 motor neuron degeneration has not been explored, yet. The present study aimed to investigate whether PACAP prevented apoptotic cell death induced by growth factor deprivation through ADNP activation and whether the peptidergic axis can counteract the OS insult. By using an in vitro model of ALS, we demonstrated that PACAP by binding to PAC1 receptor (PAC1R) prevented motor neuron death induced by serum deprivation through induction of the ADNP expression via PKC stimulation. Furthermore, we have also demonstrated that the PACAP/ADNP axis counteracted ROS formation by inducing translocation of the Nfr2 from the cytoplasm to the nucleus. In conclusion, our study provides new insights regarding the protective role of PACAP-ADNP in ALS.}, } @article {pmid37855949, year = {2023}, author = {Suh, A and Ong, J and Kamran, SA and Waisberg, E and Paladugu, P and Zaman, N and Sarker, P and Tavakkoli, A and Lee, AG}, title = {Retina Oculomics in Neurodegenerative Disease.}, journal = {Annals of biomedical engineering}, volume = {51}, number = {12}, pages = {2708-2721}, pmid = {37855949}, issn = {1573-9686}, support = {80NSSC20K183//NASA Grant/ ; }, mesh = {Humans ; *Artificial Intelligence ; *Neurodegenerative Diseases/diagnostic imaging ; Quality of Life ; Retina/diagnostic imaging ; Tomography, Optical Coherence/methods ; Biomarkers ; }, abstract = {Ophthalmic biomarkers have long played a critical role in diagnosing and managing ocular diseases. Oculomics has emerged as a field that utilizes ocular imaging biomarkers to provide insights into systemic diseases. Advances in diagnostic and imaging technologies including electroretinography, optical coherence tomography (OCT), confocal scanning laser ophthalmoscopy, fluorescence lifetime imaging ophthalmoscopy, and OCT angiography have revolutionized the ability to understand systemic diseases and even detect them earlier than clinical manifestations for earlier intervention. With the advent of increasingly large ophthalmic imaging datasets, machine learning models can be integrated into these ocular imaging biomarkers to provide further insights and prognostic predictions of neurodegenerative disease. In this manuscript, we review the use of ophthalmic imaging to provide insights into neurodegenerative diseases including Alzheimer Disease, Parkinson Disease, Amyotrophic Lateral Sclerosis, and Huntington Disease. We discuss recent advances in ophthalmic technology including eye-tracking technology and integration of artificial intelligence techniques to further provide insights into these neurodegenerative diseases. Ultimately, oculomics opens the opportunity to detect and monitor systemic diseases at a higher acuity. Thus, earlier detection of systemic diseases may allow for timely intervention for improving the quality of life in patients with neurodegenerative disease.}, } @article {pmid37855870, year = {2024}, author = {Borghero, G and Pili, F and Muroni, A and Ercoli, T and Pateri, MI and Pilotto, S and Maccabeo, A and Defazio, G}, title = {Disease survival and progression in TARDBP ALS patients from Sardinia, Italy.}, journal = {Journal of neurology}, volume = {271}, number = {2}, pages = {929-934}, pmid = {37855870}, issn = {1432-1459}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/epidemiology/genetics ; C9orf72 Protein/genetics ; Delayed Diagnosis ; Disease Progression ; Italy/epidemiology ; Mutation/genetics ; Phenotype ; }, abstract = {BACKGROUND: Common genes implicated in amyotrophic lateral sclerosis (ALS) development may also influence its progression rate. The C9orf72 mutations featured a faster progression rate while the European SOD1 mutations were associated with a slower progression. In this study, we assessed the relationship between TARDBP and ALS progression/survival.

METHODS: ALS incident patients (2010-2019) were diagnosed by El Escorial revised criteria and staged over the disease course by the King's staging system. Disease progression was analysed by Kaplan-Meier survival curves and Cox regression models, with survival measured from symptom onset to death/tracheostomy or censor date.

RESULTS: The study population included 76 patients carrying TARDBP mutations (A382T/G295S), 28 patients carrying the C9orf72 GGGGCC expansion, and 158 patients who had no evidence of causative genetic mutations (nmALS group). TARDBP patients reached death/tracheostomy later than C9orf72 and nmALS patients, independently of possible prognostic indicators (sex, age at ALS onset, diagnostic delay, phenotype at onset, and family history of ALS). On King's staging, the time elapsed between disease onset (King's stage 1) and involvement of the second body region (King's stage 2B) was similar in TARDBP and nmALS patients but longer in TARDBP than in C9orf72 patients. TARDBP patients reached King's stages 3 and 4 later than C9orf72 and nmALS patients.

CONCLUSIONS: TARDBP patients have a better survival/prognosis than C9orf72-positive and nmALS patients. King's staging also suggested that the higher survival rate and the slower progression associated with the TARDBP mutation could mainly be attributed to the longer time elapsed between King's stages 2B to 3.}, } @article {pmid37855859, year = {2024}, author = {Vieira, TCRG and Barros, CA and Domingues, R and Outeiro, TF}, title = {PrP meets alpha-synuclein: Molecular mechanisms and implications for disease.}, journal = {Journal of neurochemistry}, volume = {168}, number = {8}, pages = {1625-1639}, doi = {10.1111/jnc.15992}, pmid = {37855859}, issn = {1471-4159}, support = {SFB1286 (B8)//Deutsche Forschungsgemeinschaft/ ; EXC 2067/1-390729940//Deutsche Forschungsgemeinschaft/ ; //Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ)/ ; //Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)/ ; }, mesh = {Humans ; *alpha-Synuclein/metabolism ; Animals ; Synucleinopathies/metabolism/pathology ; Prion Proteins/metabolism ; }, abstract = {The discovery of prions has challenged dogmas and has revolutionized our understanding of protein-misfolding diseases. The concept of self-propagation via protein conformational changes, originally discovered for the prion protein (PrP), also applies to other proteins that exhibit similar behavior, such as alpha-synuclein (aSyn), a central player in Parkinson's disease and in other synucleinopathies. aSyn pathology appears to spread from one cell to another during disease progression, and involves the misfolding and aggregation of aSyn. How the transfer of aSyn between cells occurs is still being studied, but one important hypothesis involves receptor-mediated transport. Interestingly, recent studies indicate that the cellular prion protein (PrP[C]) may play a crucial role in this process. PrP[C] has been shown to act as a receptor/sensor for protein aggregates in different neurodegenerative disorders, including Alzheimer's disease and amyotrophic lateral sclerosis. Here, we provide a comprehensive overview of the current state of knowledge regarding the interaction between aSyn and PrP[C] and discuss its role in synucleinopathies. We examine the properties of PrP and aSyn, including their structure, function, and aggregation. Additionally, we discuss the current understanding of PrP[C]'s role as a receptor/sensor for aSyn aggregates and identify remaining unanswered questions in this area of research. Ultimately, we posit that exploring the interaction between aSyn and PrP[C] may offer potential treatment options for synucleinopathies.}, } @article {pmid37855109, year = {2024}, author = {Jia, H and Li, Z and Liu, H and Ren, M and Liu, T and Zhou, X and Li, X and Li, R and Liu, Q and Liu, Y and Dong, H}, title = {The Beaumont behavioral intervention in a Chinese amyotrophic lateral sclerosis cohort.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {25}, number = {1-2}, pages = {88-95}, doi = {10.1080/21678421.2023.2271518}, pmid = {37855109}, issn = {2167-9223}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/epidemiology/complications ; *Frontotemporal Dementia/diagnosis ; Cross-Sectional Studies ; Sensitivity and Specificity ; *Pick Disease of the Brain ; Neuropsychological Tests ; }, abstract = {OBJECTIVE: The prevalence of behavior impairment (27.38%) in the Chinese amyotrophic lateral sclerosis (ALS) cohort is lower. We hypothesize that the screening scales used among studies might not be appropriate to diagnose behavioral disorders in ALS patients. So, we urgently need to find a behavior scale with a high detection rate designed specifically for ALS. This study aims to verify the Chinese translation of the Beaumont Behavioral Inventory (BBI) as an effective assessment in a Chinese ALS cohort.

METHODS: Ninety-eighty ALS patients and ninety-three healthy controls were included in this cross-sectional study. All participants took emotional state, overall cognitive, sleep quality and gastroenteric function, and behavioral evaluation.

RESULTS: The BBI scores showed a strong association with the amyotrophic lateral sclerosis-Frontotemporal Dementia-Questionnaire (ALS-FTD-Q) (rs = 0.71, p < 0.001) as well as a moderate correlation with the Frontal Behavioral Inventory (FBI) (rs = 0.55, p < 0.001). High internal consistency was demonstrated in patients using BBI-after items (Cronbach's a = 0.89). When tested against clinical diagnoses, the optimal cutoff of total BBI score was identified at 5.5 (AUC = 0.95; SE = 0.02; 95% CI [0.91, 0.99]), the BBI reached optimal sensitivity and specificity values (91.5% and 87.2%). The BBI turned out to be more precise than the FBI (AUC = 0.76; SE = 0.05; 95% CI [0.66, 0.86]) and the ALS-FTD-Q (AUC = 0.84; SE = 0.04; 95% CI [0.77, 0.92]).

CONCLUSION: The Chinese version of BBI is a quicker and more efficient instrument for assessing behavioral impairment in the ALS population in China.}, } @article {pmid37853696, year = {2023}, author = {Ingólfsson, HI and Rizuan, A and Liu, X and Mohanty, P and Souza, PCT and Marrink, SJ and Bowers, MT and Mittal, J and Berry, J}, title = {Multiscale simulations reveal TDP-43 molecular-level interactions driving condensation.}, journal = {Biophysical journal}, volume = {122}, number = {22}, pages = {4370-4381}, pmid = {37853696}, issn = {1542-0086}, support = {R01 NS116176/NS/NINDS NIH HHS/United States ; }, mesh = {Humans ; Protein Domains ; *Amyotrophic Lateral Sclerosis/metabolism ; DNA-Binding Proteins/metabolism ; Molecular Dynamics Simulation ; Amyloid ; }, abstract = {The RNA-binding protein TDP-43 is associated with mRNA processing and transport from the nucleus to the cytoplasm. TDP-43 localizes in the nucleus as well as accumulating in cytoplasmic condensates such as stress granules. Aggregation and formation of amyloid-like fibrils of cytoplasmic TDP-43 are hallmarks of numerous neurodegenerative diseases, most strikingly present in >90% of amyotrophic lateral sclerosis (ALS) patients. If excessive accumulation of cytoplasmic TDP-43 causes, or is caused by, neurodegeneration is presently not known. In this work, we use molecular dynamics simulations at multiple resolutions to explore TDP-43 self- and cross-interaction dynamics. A full-length molecular model of TDP-43, all 414 amino acids, was constructed from select structures of the protein functional domains (N-terminal domain, and two RNA recognition motifs, RRM1 and RRM2) and modeling of disordered connecting loops and the low complexity glycine-rich C-terminus domain. All-atom CHARMM36m simulations of single TDP-43 proteins served as guides to construct a coarse-grained Martini 3 model of TDP-43. The Martini model and a coarser implicit solvent C⍺ model, optimized for disordered proteins, were subsequently used to probe TDP-43 interactions; self-interactions from single-chain full-length TDP-43 simulations, cross-interactions from simulations with two proteins and simulations with assemblies of dozens to hundreds of proteins. Our findings illustrate the utility of different modeling scales for accessing TDP-43 molecular-level interactions and suggest that TDP-43 has numerous interaction preferences or patterns, exhibiting an overall strong, but dynamic, association and driving the formation of biomolecular condensates.}, } @article {pmid37852234, year = {2023}, author = {Sueda, T and Tei, M and Mori, S and Nishida, K and Yasuyama, A and Nomura, M and Yoshikawa, Y and Tsujie, M}, title = {Clinical Impact of Transanal Drainage Tube on Anastomosis Leakage Following Minimally Invasive Resection Without Diverting Stoma in Patients With Rectal Cancer: A Propensity Score-matched Analysis.}, journal = {Surgical laparoscopy, endoscopy & percutaneous techniques}, volume = {33}, number = {6}, pages = {608-616}, doi = {10.1097/SLE.0000000000001237}, pmid = {37852234}, issn = {1534-4908}, mesh = {Humans ; *Anastomotic Leak/etiology/prevention & control/surgery ; Anastomosis, Surgical/adverse effects/methods ; Retrospective Studies ; Propensity Score ; *Rectal Neoplasms/surgery/complications ; Drainage/methods ; }, abstract = {OBJECTIVES: As one of the most serious complications of rectal cancer (RC) surgery, preventing anastomotic leakage (AL) is crucial. Several studies have suggested a positive role of the transanal drainage tube (TaDT) in AL prevention. However, whether TaDT is beneficial for AL in patients with RC remains controversial. The present study aimed to evaluate the clinical impact of TaDT on AL following minimally invasive resection without diverting stoma (DS) in patients with RC.

MATERIALS AND METHODS: We retrospectively analyzed 392 consecutive patients with RC who had undergone minimally invasive resection without DS between 2010 and 2021. Propensity score matching (PSM) was performed to reduce selection bias. AL was classified as grade A, B, or C.

RESULTS: A TaDT was used in 214 patients overall. After PSM, we enrolled 316 patients (n=158 in each group). Before PSM, significant group-dependent differences were observed in terms of age, American Society of Anesthesiologists physical status, and the use of antiplatelet/anticoagulant agents. The frequency of AL was 7.3% in the overall cohort and was significantly lower in the TaDT group (3.7%) than in the non-TaDT group (11.8%). The rate of grade B AL was significantly lower in the TaDT group than in the non-TaDT group (before PSM, P <0.01; after PSM, P =0.02). However, no significant differences between groups were found for grade C AL. Moreover, multivariate analysis identified the lack of a TaDT as an independent risk factor for AL in the overall and matched cohorts [before PSM, odds ratio, 3.64, P <0.01; after PSM, odds ratio, 2.91, P =0.02].

CONCLUSION: These results indicated that TaDT may play a beneficial role in preventing AL, particularly of grade B, for patients with RC undergoing minimally invasive resection without DS. However, further randomized controlled trials, including patient-reported outcomes, are still needed to understand better the role of TaDT in preventing ALs in patients with RC undergoing minimally invasive resection without DS.}, } @article {pmid37851044, year = {2023}, author = {Gwathmey, K and Heiman-Patterson, TD}, title = {Multidisciplinary Clinics in Neuromuscular Medicine.}, journal = {Continuum (Minneapolis, Minn.)}, volume = {29}, number = {5}, pages = {1585-1594}, pmid = {37851044}, issn = {1538-6899}, mesh = {Humans ; Quality of Life ; *Telemedicine ; *Amyotrophic Lateral Sclerosis/diagnosis ; Ambulatory Care ; *Neuromuscular Diseases/diagnosis/therapy ; }, abstract = {Multidisciplinary care is comprehensive, coordinated clinical care across medical disciplines and allied health professions. Neuromuscular disorders, such as amyotrophic lateral sclerosis and muscular dystrophies, are often associated with disabling weakness and extramuscular symptoms and may benefit from care in a model that consolidates numerous clinic visits into a single more efficient multidisciplinary clinic visit. The goal of the neuromuscular multidisciplinary care model is to improve patient outcomes, patient satisfaction, quality of life, access to medications and equipment, and survival. Although the costs of running a multidisciplinary clinic are high, they are likely associated with cost savings from the patient's perspective. Several barriers to acceptance of multidisciplinary clinics include the distance needed to travel to the clinic and the duration of the clinic visit. Telehealth multidisciplinary clinic visits may address some of these concerns. Further study is needed to understand the value of multidisciplinary clinics and is a necessary step toward creating a sustainable model.}, } @article {pmid37851042, year = {2023}, author = {Izenberg, A}, title = {Amyotrophic Lateral Sclerosis and Other Motor Neuron Diseases.}, journal = {Continuum (Minneapolis, Minn.)}, volume = {29}, number = {5}, pages = {1538-1563}, pmid = {37851042}, issn = {1538-6899}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/genetics/therapy ; *Motor Neuron Disease/diagnosis/genetics/therapy ; Biomarkers ; }, abstract = {OBJECTIVE: This article reviews the clinical spectrum of amyotrophic lateral sclerosis (ALS), its variant presentations, and the approach to diagnosis and management. This review includes a detailed discussion of current and emerging disease-modifying therapies and the management of respiratory and bulbar manifestations of disease. An updated review of ALS genetics and pathophysiology is also provided. This article also touches on several other important motor neuron diseases.

LATEST DEVELOPMENTS: A new set of simplified diagnostic criteria may help identify patients at earlier stages of the disease. A coformulation of sodium phenylbutyrate and tauroursodeoxycholic acid has been shown to have a significant benefit on disease progression and survival, leading to approval by regulatory authorities in the United States and Canada. An oral formulation of edaravone and an antisense oligonucleotide to a SOD1 gene variation (tofersen) have also recently been approved by the US Food and Drug Administration (FDA). Phase 3 trials of intrathecal mesenchymal stem cells failed to meet primary end points for efficacy. Updated American Academy of Neurology quality measures for the care of patients with ALS were published in 2023.

ESSENTIAL POINTS: There has been continued progress in ALS genetics, diagnosis, and disease-modifying therapies. However, we still lack a definitive biomarker or a treatment that can halt the progression or reverse the course of disease. The evolving understanding of the genetic and pathophysiologic underpinnings of disease offers promise for more effective and clinically meaningful treatments in the future.}, } @article {pmid37850654, year = {2024}, author = {Chen, S and Huan, X and Xu, CZ and Luo, SS and Zhao, CB and Zhong, HH and Zheng, XY and Qiao, K and Dong, Y and Wang, Y and Liu, CY and Huang, HP and Chen, Y and Zou, ZY}, title = {Eomesodermin expression in CD4[+]T-cells associated with disease progression in amyotrophic lateral sclerosis.}, journal = {CNS neuroscience & therapeutics}, volume = {30}, number = {4}, pages = {e14503}, pmid = {37850654}, issn = {1755-5949}, support = {81901286, 81974199, 82271458//National Natural Science Foundation of China/ ; 2018Y9026, 2021Y9065//The Joint Funds for the innovation of science and Technology, Fujian province/ ; 2018QH1032//The Startup Fund for scientific research, Fujian Medical University/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/blood/diagnosis/immunology ; Biomarkers ; Disease Progression ; Longitudinal Studies ; Prognosis ; T-Lymphocytes ; *T-Box Domain Proteins/metabolism ; *CD4-Positive T-Lymphocytes/immunology/metabolism ; }, abstract = {AIM: To clarify the role of Eomesodermin (EOMES) to serve as a disease-relevant biomarker and the intracellular molecules underlying the immunophenotype shifting of CD4[+]T subsets in amyotrophic lateral sclerosis (ALS).

METHODS: The derivation and validation cohorts included a total of 148 ALS patients and 101 healthy controls (HCs). Clinical data and peripheral blood were collected. T-cell subsets and the EOMES expression were quantified using multicolor flow cytometry. Serum neurofilament light chain (NFL) was measured. In 1-year longitudinal follow-ups, the ALSFRS-R scores and primary endpoint events were further recorded in the ALS patients of the validation cohort.

RESULTS: In the derivation cohort, the CD4[+]EOMES[+]T-cell subsets were significantly increased (p < 0.001). EOMES[+] subset was positively correlated with increased serum NFL levels in patients with onset longer than 12 months. In the validation cohort, the elevated CD4[+]EOMES[+]T-cell proportions and their association with NFL levels were also identified. The longitudinal study revealed that ALS patients with higher EOMES expression were associated with higher progression rates (p = .010) and worse prognosis (p = .003).

CONCLUSIONS: We demonstrated that increased CD4[+]EOMES[+]T-cell subsets in ALS were associated with disease progression and poor prognosis. Identifying these associations may contribute to a better understanding of the immunopathological mechanism of ALS.}, } @article {pmid37849894, year = {2023}, author = {Fang, M and Deibler, SK and Nana, AL and Vatsavayai, SC and Banday, S and Zhou, Y and Almeida, S and Weiss, A and Brown, RH and Seeley, WW and Gao, FB and Green, MR}, title = {Loss of TDP-43 function contributes to genomic instability in amyotrophic lateral sclerosis.}, journal = {Frontiers in neuroscience}, volume = {17}, number = {}, pages = {1251228}, pmid = {37849894}, issn = {1662-4548}, support = {R01 NS104437/NS/NINDS NIH HHS/United States ; RF1 NS101986/NS/NINDS NIH HHS/United States ; U01 AG057195/AG/NIA NIH HHS/United States ; R01 GM035490/GM/NIGMS NIH HHS/United States ; R21 NS119952/NS/NINDS NIH HHS/United States ; U19 AG063911/AG/NIA NIH HHS/United States ; P30 AG062422/AG/NIA NIH HHS/United States ; P01 AG019724/AG/NIA NIH HHS/United States ; R37 NS057553/NS/NINDS NIH HHS/United States ; R21 NS112766/NS/NINDS NIH HHS/United States ; R01 NS101986/NS/NINDS NIH HHS/United States ; }, abstract = {A common pathological hallmark of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) is the cytoplasmic mislocalization and aggregation of the DNA/RNA-binding protein TDP-43, but how loss of nuclear TDP-43 function contributes to ALS and FTD pathogenesis remains largely unknown. Here, using large-scale RNAi screening, we identify TARDBP, which encodes TDP-43, as a gene whose loss-of-function results in elevated DNA mutation rate and genomic instability. Consistent with this finding, we observe increased DNA damage in induced pluripotent stem cells (iPSCs) and iPSC-derived post-mitotic neurons generated from ALS patients harboring TARDBP mutations. We find that the increase in DNA damage in ALS iPSC-derived neurons is due to defects in two major pathways for DNA double-strand break repair: non-homologous end joining and homologous recombination. Cells with defects in DNA repair are sensitive to DNA damaging agents and, accordingly, we find that ALS iPSC-derived neurons show a marked reduction in survival following treatment with a DNA damaging agent. Importantly, we find that increased DNA damage is also observed in neurons with nuclear TDP-43 depletion from ALS/FTD patient brain tissues. Collectively, our results demonstrate that ALS neurons with loss of nuclear TDP-43 function have elevated levels of DNA damage and contribute to the idea that genomic instability is a defining pathological feature of ALS/FTD patients with TDP-43 pathology.}, } @article {pmid37849367, year = {2023}, author = {Takagi, S and Daimon, S and Inoue, K and Umeda, M and Kobayashi, Z}, title = {[A Case of Amyotrophic Lateral Sclerosis with Semantic Variant Primary Progressive Aphasia: A Study of Language Symptoms and Agraphia].}, journal = {Brain and nerve = Shinkei kenkyu no shinpo}, volume = {75}, number = {10}, pages = {1155-1161}, doi = {10.11477/mf.1416202493}, pmid = {37849367}, issn = {1881-6096}, mesh = {Male ; Humans ; Aged ; *Agraphia/etiology ; Semantics ; *Amyotrophic Lateral Sclerosis/complications ; Language ; Magnetic Resonance Imaging/adverse effects ; *Aphasia, Primary Progressive/diagnostic imaging/complications ; Atrophy/complications ; }, abstract = {The patient was a 66-year-old man brought to the emergency room with impaired consciousness due to hypercarbonemia, managed on a respirator, and diagnosed with amyotrophic lateral sclerosis (ALS). MRI showed atrophy of the anterior and medial surfaces of the bilateral temporal lobes that was more severe in the right side. The patient had dysgraphia in both kana and kanji. Detailed examinations of the language function revealed impaired single-word comprehension, impaired naming, and surface dysgraphia, leading to the diagnosis of semantic variant primary progressive aphasia (svPPA). ALS patients with atrophy of the anterior temporal lobe and surface dysgraphia of kanji may have svPPA as a complication. (Received April 14, 2023; Accepted June 21, 2023; Published October 1, 2023).}, } @article {pmid37849306, year = {2024}, author = {Olsen, CG and Busk, ØL and Holla, ØL and Tveten, K and Holmøy, T and Tysnes, OB and Høyer, H}, title = {Genetic overlap between ALS and other neurodegenerative or neuromuscular disorders.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {25}, number = {1-2}, pages = {177-187}, doi = {10.1080/21678421.2023.2270705}, pmid = {37849306}, issn = {2167-9223}, mesh = {Humans ; Genetic Predisposition to Disease/genetics ; *Amyotrophic Lateral Sclerosis/epidemiology/genetics ; Genetic Association Studies ; Family ; *Neurodegenerative Diseases/epidemiology/genetics ; ATPases Associated with Diverse Cellular Activities/genetics ; ATP-Dependent Proteases/genetics ; LDL-Receptor Related Proteins/genetics ; Membrane Transport Proteins/genetics ; Kinesins/genetics ; Cytoskeletal Proteins/genetics ; *Cell Cycle Proteins ; }, abstract = {OBJECTIVE: In Norway, 89% of patients with Amyotrophic lateral sclerosis (ALS) lacks a genetic diagnose. ALS genes and genes that cause other neuromuscular or neurodegenerative disorders extensively overlap. This population-based study examined whether patients with ALS have a family history of neurological disorders and explored the occurrence of rare genetic variants associated with other neurodegenerative or neuromuscular disorders.

METHODS: During a two-year period, blood samples and clinical data from patients with ALS were collected from all 17 neurological departments in Norway. Our genetic analysis involved exome sequencing and bioinformatics filtering of 510 genes associated with neurodegenerative and neuromuscular disorders. The variants were interpreted using genotype-phenotype correlations and bioinformatics tools.

RESULTS: A total of 279 patients from a Norwegian population-based ALS cohort participated in this study. Thirty-one percent of the patients had first- or second-degree relatives with other neurodegenerative disorders, most commonly dementia and Parkinson's disease. The genetic analysis identified 20 possible pathogenic variants, in ATL3, AFG3L2, ATP7A, BICD2, HARS1, KIF1A, LRRK2, MSTO1, NEK1, NEFH, and SORL1, in 25 patients. NEK1 risk variants were present in 2.5% of this ALS cohort. Only four of the 25 patients reported relatives with other neurodegenerative or neuromuscular disorders.

CONCLUSION: Gene variants known to cause other neurodegenerative or neuromuscular disorders, most frequently in NEK1, were identified in 9% of the patients with ALS. Most of these patients had no family history of other neurodegenerative or neuromuscular disorders. Our findings indicated that AFG3L2, ATP7A, BICD2, KIF1A, and MSTO1 should be further explored as potential ALS-causing genes.}, } @article {pmid37847372, year = {2023}, author = {Sattler, R and Traynor, BJ and Robertson, J and Van Den Bosch, L and Barmada, SJ and Svendsen, CN and Disney, MD and Gendron, TF and Wong, PC and Turner, MR and Boxer, A and Babu, S and Benatar, M and Kurnellas, M and Rohrer, JD and Donnelly, CJ and Bustos, LM and Van Keuren-Jensen, K and Dacks, PA and Sabbagh, MN and , }, title = {Roadmap for C9ORF72 in Frontotemporal Dementia and Amyotrophic Lateral Sclerosis: Report on the C9ORF72 FTD/ALS Summit.}, journal = {Neurology and therapy}, volume = {12}, number = {6}, pages = {1821-1843}, pmid = {37847372}, issn = {2193-8253}, support = {RF1 NS114128/NS/NINDS NIH HHS/United States ; ZIAAG000933-15/AG/NIA NIH HHS/United States ; TURNER/OCT18/989-797/MNDA_/Motor Neurone Disease Association/United Kingdom ; MR/M008525/1/MRC_/Medical Research Council/United Kingdom ; MR/T046015/1/MRC_/Medical Research Council/United Kingdom ; R35 NS116846/NS/NINDS NIH HHS/United States ; ZIA AG000933/ImNIH/Intramural NIH HHS/United States ; }, abstract = {A summit held March 2023 in Scottsdale, Arizona (USA) focused on the intronic hexanucleotide expansion in the C9ORF72 gene and its relevance in frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS; C9ORF72-FTD/ALS). The goal of this summit was to connect basic scientists, clinical researchers, drug developers, and individuals affected by C9ORF72-FTD/ALS to evaluate how collaborative efforts across the FTD-ALS disease spectrum might break down existing disease silos. Presentations and discussions covered recent discoveries in C9ORF72-FTD/ALS disease mechanisms, availability of disease biomarkers and recent advances in therapeutic development, and clinical trial design for prevention and treatment for individuals affected by C9ORF72-FTD/ALS and asymptomatic pathological expansion carriers. The C9ORF72-associated hexanucleotide repeat expansion is an important locus for both ALS and FTD. C9ORF72-FTD/ALS may be characterized by loss of function of the C9ORF72 protein and toxic gain of functions caused by both dipeptide repeat (DPR) proteins and hexanucleotide repeat RNA. C9ORF72-FTD/ALS therapeutic strategies discussed at the summit included the use of antisense oligonucleotides, adeno-associated virus (AAV)-mediated gene silencing and gene delivery, and engineered small molecules targeting RNA structures associated with the C9ORF72 expansion. Neurofilament light chain, DPR proteins, and transactive response (TAR) DNA-binding protein 43 (TDP-43)-associated molecular changes were presented as biomarker candidates. Similarly, brain imaging modalities (i.e., magnetic resonance imaging [MRI] and positron emission tomography [PET]) measuring structural, functional, and metabolic changes were discussed as important tools to monitor individuals affected with C9ORF72-FTD/ALS, at both pre-symptomatic and symptomatic disease stages. Finally, summit attendees evaluated current clinical trial designs available for FTD or ALS patients and concluded that therapeutics relevant to FTD/ALS patients, such as those specifically targeting C9ORF72, may need to be tested with composite endpoints covering clinical symptoms of both FTD and ALS. The latter will require novel clinical trial designs to be inclusive of all patient subgroups spanning the FTD/ALS spectrum.}, } @article {pmid37845811, year = {2024}, author = {Holt, MW and Robinson, EC and Shlobin, NA and Hanson, JT and Bozkurt, I}, title = {Intracortical brain-computer interfaces for improved motor function: a systematic review.}, journal = {Reviews in the neurosciences}, volume = {35}, number = {2}, pages = {213-223}, pmid = {37845811}, issn = {2191-0200}, mesh = {Humans ; *Brain-Computer Interfaces ; *Motor Cortex/physiology/physiopathology ; }, abstract = {In this systematic review, we address the status of intracortical brain-computer interfaces (iBCIs) applied to the motor cortex to improve function in patients with impaired motor ability. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 Guidelines for Systematic Reviews. Risk Of Bias In Non-randomized Studies - of Interventions (ROBINS-I) and the Effective Public Health Practice Project (EPHPP) were used to assess bias and quality. Advances in iBCIs in the last two decades demonstrated the use of iBCI to activate limbs for functional tasks, achieve neural typing for communication, and other applications. However, the inconsistency of performance metrics employed by these studies suggests the need for standardization. Each study was a pilot clinical trial consisting of 1-4, majority male (64.28 %) participants, with most trials featuring participants treated for more than 12 months (55.55 %). The systems treated patients with various conditions: amyotrophic lateral sclerosis, stroke, spinocerebellar degeneration without cerebellar involvement, and spinal cord injury. All participants presented with tetraplegia at implantation and were implanted with microelectrode arrays via pneumatic insertion, with nearly all electrode locations solely at the precentral gyrus of the motor cortex (88.88 %). The development of iBCI devices using neural signals from the motor cortex to improve motor-impaired patients has enhanced the ability of these systems to return ability to their users. However, many milestones remain before these devices can prove their feasibility for recovery. This review summarizes the achievements and shortfalls of these systems and their respective trials.}, } @article {pmid37845749, year = {2023}, author = {Bennett, CL and Dastidar, S and Arnold, FJ and McKinstry, SU and Stockford, C and Freibaum, BD and Sopher, BL and Wu, M and Seidner, G and Joiner, W and Taylor, JP and West, RJH and La Spada, AR}, title = {Senataxin helicase, the causal gene defect in ALS4, is a significant modifier of C9orf72 ALS G4C2 and arginine-containing dipeptide repeat toxicity.}, journal = {Acta neuropathologica communications}, volume = {11}, number = {1}, pages = {164}, pmid = {37845749}, issn = {2051-5960}, support = {R01 GM125080/GM/NIGMS NIH HHS/United States ; R35 NS122140/NS/NINDS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Humans ; Animals ; *Amyotrophic Lateral Sclerosis/metabolism ; Dipeptides/genetics ; C9orf72 Protein/genetics/metabolism ; Arginine/genetics/metabolism ; HEK293 Cells ; Motor Neurons/metabolism ; Drosophila/metabolism ; RNA/metabolism ; *Frontotemporal Dementia/genetics ; DNA Repeat Expansion/genetics ; DNA Helicases/genetics ; RNA Helicases/genetics ; Multifunctional Enzymes/genetics ; }, abstract = {Identifying genetic modifiers of familial amyotrophic lateral sclerosis (ALS) may reveal targets for therapeutic modulation with potential application to sporadic ALS. GGGGCC (G4C2) repeat expansions in the C9orf72 gene underlie the most common form of familial ALS, and generate toxic arginine-containing dipeptide repeats (DPRs), which interfere with membraneless organelles, such as the nucleolus. Here we considered senataxin (SETX), the genetic cause of ALS4, as a modifier of C9orf72 ALS, because SETX is a nuclear helicase that may regulate RNA-protein interactions involved in ALS dysfunction. After documenting that decreased SETX expression enhances arginine-containing DPR toxicity and C9orf72 repeat expansion toxicity in HEK293 cells and primary neurons, we generated SETX fly lines and evaluated the effect of SETX in flies expressing either (G4C2)58 repeats or glycine-arginine-50 [GR(50)] DPRs. We observed dramatic suppression of disease phenotypes in (G4C2)58 and GR(50) Drosophila models, and detected a striking relocalization of GR(50) out of the nucleolus in flies co-expressing SETX. Next-generation GR(1000) fly models, that show age-related motor deficits in climbing and movement assays, were similarly rescued with SETX co-expression. We noted that the physical interaction between SETX and arginine-containing DPRs is partially RNA-dependent. Finally, we directly assessed the nucleolus in cells expressing GR-DPRs, confirmed reduced mobility of proteins trafficking to the nucleolus upon GR-DPR expression, and found that SETX dosage modulated nucleolus liquidity in GR-DPR-expressing cells and motor neurons. These findings reveal a hitherto unknown connection between SETX function and cellular processes contributing to neuron demise in the most common form of familial ALS.}, } @article {pmid37845449, year = {2023}, author = {Shin, J and Kang, H and Kim, S}, title = {Primo Vessels Inside Lymphatic Vessels Are Absent in an ALS Mouse Model.}, journal = {Advances in experimental medicine and biology}, volume = {1438}, number = {}, pages = {113-117}, pmid = {37845449}, issn = {0065-2598}, mesh = {Mice ; Animals ; *Amyotrophic Lateral Sclerosis ; *Neurodegenerative Diseases ; *Lymphatic Vessels ; Lymph Nodes ; Oxygen/analysis ; Disease Models, Animal ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the selective death of motor neurons in the central nervous system. It is also a representative rare disease among degenerative diseases of the nervous system. Although many drugs for the treatment of degenerative brain diseases are being developed, they are not delivered correctly to the target due to the blood-brain barrier. The present study aimed to analyze changes in the primo vascular system (PVS) in ALS mice with symptoms and the partial oxygen pressure (pO2) in normal mice. In normal mice, we consistently observed primo vessels in lymphatic vessels (L-PVS). However, in ALS mice with symptoms, L-PVS were mostly lost, rendering them difficult to observe. The pO2 of the L-PVS in normal mice was significantly higher than that of normal dermis and lymph nodes.In conclusion, the relatively higher oxygen levels measured in the L-PVS than in normal dermis and lymph nodes suggest a role for the PVS in oxygen transport and enable a hypothesis that the L-PVS can function as a drug delivery pathway.}, } @article {pmid37845420, year = {2024}, author = {Zhang, J and Liu, Y and Xu, G and Cao, X and Wang, W and Zhang, D and Zhu, M}, title = {Causal relationship between coffee intake and neurological diseases: a Mendelian randomization study.}, journal = {European journal of clinical nutrition}, volume = {78}, number = {2}, pages = {114-119}, pmid = {37845420}, issn = {1476-5640}, support = {82260225//National Natural Science Foundation of China (National Science Foundation of China)/ ; 20202BAB216043//Natural Science Foundation of Jiangxi Province (Jiangxi Province Natural Science Foundation)/ ; }, mesh = {Humans ; Coffee/adverse effects ; Mendelian Randomization Analysis ; *Nervous System Diseases/etiology/genetics ; *Migraine Disorders/genetics ; Causality ; }, abstract = {BACKGROUND: Previous observational studies focused on the association of coffee consumption and neurological disease. However, it is not known whether these associations are causal.

METHODS: We used Mendelian randomization (MR) study to assess the causal relationship of coffee intake with the risk of neurological diseases, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis, epilepsy, stroke, and migraine. Single-nucleotide polymorphisms (SNPs) which had genetic statistical significance with coffee intake were used as instrumental variable (IV). Genetic instruments were stretched from the MRC-IEU (MRC Integrative Epidemiology Unit) analysis on the UK Biobank. We performed MR analyses using the inverse variance weighted (IVW) method as the main approach. Sensitivity analyses were further performed using MR-Egger and MR-PRESSO to assess the robustness.

RESULTS: In the MR analysis, 40 SNPs were selected as IV, the F statistics for all SNPs ranged from 16 to 359. In IVW approach, our results provide genetic evidence supporting a potential causal association between coffee intake and a lower risk of migraine (OR = 0.528, 95% CI = 0.342-0.817, P = 0.004) and migraine with aura (OR = 0.374, 95% CI = 0.208-0.672, P = 0.001). However, we found no significant association between coffee intake and other neurological diseases along with their subtypes in this MR study.

CONCLUSION: Using genetic data, our MR study found significant evidence supporting a causal association between coffee intake and migraine. This suggests that coffee consumption is likely a trigger or a prevention strategy for migraine.}, } @article {pmid37845101, year = {2023}, author = {Ugawa, Y}, title = {Somatosensory cortex/tracts involvement in amyotrophic lateral sclerosis.}, journal = {Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology}, volume = {156}, number = {}, pages = {249-250}, doi = {10.1016/j.clinph.2023.09.009}, pmid = {37845101}, issn = {1872-8952}, } @article {pmid37844546, year = {2023}, author = {Polverino, M and Sampaolo, S and Capuozzo, A and Fasolino, M and Aliberti, M and Satta, E and Santoriello, C and Orengo, JP and Polverino, F}, title = {Respiratory Function Changes as Early Signs of Amyotrophic Lateral Sclerosis.}, journal = {Respiration; international review of thoracic diseases}, volume = {102}, number = {11}, pages = {919-923}, pmid = {37844546}, issn = {1423-0356}, support = {R01 HL149744/HL/NHLBI NIH HHS/United States ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis ; Respiration ; Respiratory Function Tests ; Lung ; Exhalation ; }, abstract = {BACKGROUND: The current diagnostic criteria for amyotrophic lateral sclerosis (ALS) may remain unsatisfactory for months or years in the early disease. Pulmonary assessment has never been considered useful in the early diagnosis of ALS, and studies of pulmonary function in this patient category are lacking.

OBJECTIVES: The objective of this study was to assess the pulmonary function in subjects with unspecific symptoms of ALS in whom an ALS diagnosis cannot be reached based on the current available guidelines.

METHODS: We performed pulmonary function tests, arterial gas analysis, maximal inspiratory (MIP) and expiratory (MEP) pressure, and respiratory drive (P0.1) assessment in 35 patients with unspecific neurological symptoms at the time of the visit and those were subsequently diagnosed with ALS 2 years after the initial visit ("pre-ALS"); we compared these patients with 29 patients with established ALS and with 28 control subjects.

RESULTS: Spirometric parameters were not different between the three groups. However, MIP was significantly lower and P0.1 was significantly increased (with the ratio P0.1/MIP significantly higher) in both established and pre-ALS patients compared to controls, while both MIP and P0.1 were similar between established ALS and pre-ALS.

CONCLUSIONS: Changes in MIP, P0.1, and P0.1/MIP ratio are highly suggestive of preclinical ALS when the spirometry and neurodiagnostic tests are still inconclusive. MIP and P0.1 are noninvasive measurements that can be easily assessed in an ambulatory setting. Future studies on larger cohorts are needed to validate the use of these parameters in the preclinical diagnosis of ALS as well as in other neuromuscular diseases.}, } @article {pmid37844376, year = {2023}, author = {Qassim, HM and Seyedalipour, B and Baziyar, P and Ahamady-Asbchin, S}, title = {Polyphenolic flavonoid compounds act as the inhibitory potential of aggregation process: Implications for the prevention and therapeutics against FALS-associated D101G SOD1 mutant.}, journal = {Computational biology and chemistry}, volume = {107}, number = {}, pages = {107967}, doi = {10.1016/j.compbiolchem.2023.107967}, pmid = {37844376}, issn = {1476-928X}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy/genetics/metabolism ; Superoxide Dismutase-1/genetics/chemistry/metabolism ; *Hesperidin/pharmacology ; Superoxide Dismutase/chemistry/genetics/metabolism ; Mutation ; }, abstract = {Aggregation of proteins is a biological phenomenon caused by misfolded proteins. Human superoxide dismutase (hSOD1) misfolding and aggregation underlie the neurological illness amyotrophic lateral sclerosis (ALS). The most significant contributing factor to ALS is genetic point mutations in SOD1. particularly, D101G mutant is the most harmful because it significantly reduces the life expectancy of patients. Subsequently, the use of natural polyphenolic flavonoids is strongly recommended to reduce the amyloidogenic behavior of protopathic proteins. In this study, using computational parameters such as protein-ligand interaction and molecular dynamics (MD) simulation analyses, we are trying to identify a pharmacodynamically promising flavonoid compound that can effectively inhibit the pathogenic behavior of the D101G mutant. Epigallocatechin-gallate (EGCG), Hesperidin, Isorhamnetin, and Diosmetin were identified as potential leads in a preliminary screening of flavonoids to anti-amyloid action. The results of MD showed that the binding of flavonoids to D101G mutant caused changes in stability, hydrophobicity of protein, and flexibility, as well as significantly led to the restoration of lost hydrogen bonds. Secondary structure analysis showed that protein destabilization and the increased propensity of β-sheet caused by the mutation were restored to the wild-type state upon binding of flavonoids. Besides, to differentiate aggregation, we elucidated alterations in the free energy landscape (FEL) and dynamic cross-correlation matrix (DCCM) of WT-SOD1 and mutant (unbound /bound) states. Among flavonoids, Epigallocatechin-gallate and Hesperidin had the most therapeutic efficacy against the D101G mutant. Therefore, Epigallocatechin-gallate and Hesperidin promise considerable therapeutic potential to develop highly effective inhibitors in reducing fatal and irreversible ALS.}, } @article {pmid37843219, year = {2024}, author = {Liu, X and Liu, Y and Liu, J and Zhang, H and Shan, C and Guo, Y and Gong, X and Cui, M and Li, X and Tang, M}, title = {Correlation between the gut microbiome and neurodegenerative diseases: a review of metagenomics evidence.}, journal = {Neural regeneration research}, volume = {19}, number = {4}, pages = {833-845}, pmid = {37843219}, issn = {1673-5374}, abstract = {A growing body of evidence suggests that the gut microbiota contributes to the development of neurodegenerative diseases via the microbiota-gut-brain axis. As a contributing factor, microbiota dysbiosis always occurs in pathological changes of neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. High-throughput sequencing technology has helped to reveal that the bidirectional communication between the central nervous system and the enteric nervous system is facilitated by the microbiota's diverse microorganisms, and for both neuroimmune and neuroendocrine systems. Here, we summarize the bioinformatics analysis and wet-biology validation for the gut metagenomics in neurodegenerative diseases, with an emphasis on multi-omics studies and the gut virome. The pathogen-associated signaling biomarkers for identifying brain disorders and potential therapeutic targets are also elucidated. Finally, we discuss the role of diet, prebiotics, probiotics, postbiotics and exercise interventions in remodeling the microbiome and reducing the symptoms of neurodegenerative diseases.}, } @article {pmid37843214, year = {2024}, author = {Wang, X and Hu, Y and Xu, R}, title = {The pathogenic mechanism of TAR DNA-binding protein 43 (TDP-43) in amyotrophic lateral sclerosis.}, journal = {Neural regeneration research}, volume = {19}, number = {4}, pages = {800-806}, pmid = {37843214}, issn = {1673-5374}, abstract = {The onset of amyotrophic lateral sclerosis is usually characterized by focal death of both upper and/or lower motor neurons occurring in the motor cortex, basal ganglia, brainstem, and spinal cord, and commonly involves the muscles of the upper and/or lower extremities, and the muscles of the bulbar and/or respiratory regions. However, as the disease progresses, it affects the adjacent body regions, leading to generalized muscle weakness, occasionally along with memory, cognitive, behavioral, and language impairments; respiratory dysfunction occurs at the final stage of the disease. The disease has a complicated pathophysiology and currently, only riluzole, edaravone, and phenylbutyrate/taurursodiol are licensed to treat amyotrophic lateral sclerosis in many industrialized countries. The TAR DNA-binding protein 43 inclusions are observed in 97% of those diagnosed with amyotrophic lateral sclerosis. This review provides a preliminary overview of the potential effects of TAR DNA-binding protein 43 in the pathogenesis of amyotrophic lateral sclerosis, including the abnormalities in nucleoplasmic transport, RNA function, post-translational modification, liquid-liquid phase separation, stress granules, mitochondrial dysfunction, oxidative stress, axonal transport, protein quality control system, and non-cellular autonomous functions (e.g., glial cell functions and prion-like propagation).}, } @article {pmid37843208, year = {2024}, author = {King, PH}, title = {Skeletal muscle as a molecular and cellular biomarker of disease progression in amyotrophic lateral sclerosis: a narrative review.}, journal = {Neural regeneration research}, volume = {19}, number = {4}, pages = {747-753}, pmid = {37843208}, issn = {1673-5374}, support = {I01 BX001148/BX/BLRD VA/United States ; I01 BX005899/BX/BLRD VA/United States ; R01 NS092651/NS/NINDS NIH HHS/United States ; R21 NS111275/NS/NINDS NIH HHS/United States ; }, abstract = {Amyotrophic lateral sclerosis is a fatal multisystemic neurodegenerative disease with motor neurons being a primary target. Although progressive weakness is a hallmark feature of amyotrophic lateral sclerosis, there is considerable heterogeneity, including clinical presentation, progression, and the underlying triggers for disease initiation. Based on longitudinal studies with families harboring amyotrophic lateral sclerosis-associated gene mutations, it has become apparent that overt disease is preceded by a prodromal phase, possibly in years, where compensatory mechanisms delay symptom onset. Since 85-90% of amyotrophic lateral sclerosis is sporadic, there is a strong need for identifying biomarkers that can detect this prodromal phase as motor neurons have limited capacity for regeneration. Current Food and Drug Administration-approved therapies work by slowing the degenerative process and are most effective early in the disease. Skeletal muscle, including the neuromuscular junction, manifests abnormalities at the earliest stages of the disease, before motor neuron loss, making it a promising source for identifying biomarkers of the prodromal phase. The accessibility of muscle through biopsy provides a lens into the distal motor system at earlier stages and in real time. The advent of "omics" technology has led to the identification of numerous dysregulated molecules in amyotrophic lateral sclerosis muscle, ranging from coding and non-coding RNAs to proteins and metabolites. This technology has opened the door for identifying biomarkers of disease activity and providing insight into disease mechanisms. A major challenge is correlating the myriad of dysregulated molecules with clinical or histological progression and understanding their relevance to presymptomatic phases of disease. There are two major goals of this review. The first is to summarize some of the biomarkers identified in human amyotrophic lateral sclerosis muscle that have a clinicopathological correlation with disease activity, evidence of a similar dysregulation in the SOD1[G93A] mouse during presymptomatic stages, and evidence of progressive change during disease progression. The second goal is to review the molecular pathways these biomarkers reflect and their potential role in mitigating or promoting disease progression, and as such, their potential as therapeutic targets in amyotrophic lateral sclerosis.}, } @article {pmid37842553, year = {2023}, author = {Zucchi, E and Musazzi, UM and Fedele, G and Martinelli, I and Gianferrari, G and Simonini, C and Fini, N and Ghezzi, A and Caputo, M and Sette, E and Vacchiano, V and Zinno, L and Anceschi, P and Canali, E and Vinceti, M and Ferro, S and Mandrioli, J and , }, title = {Effect of tauroursodeoxycholic acid on survival and safety in amyotrophic lateral sclerosis: a retrospective population-based cohort study.}, journal = {EClinicalMedicine}, volume = {65}, number = {}, pages = {102256}, pmid = {37842553}, issn = {2589-5370}, abstract = {BACKGROUND: Oral tauroursodeoxycholic acid (TUDCA) is a commercial drug currently tested in patients with amyotrophic lateral sclerosis (ALS) both singly and combined with sodium phenylbutyrate. This retrospective study aimed to investigate, in a real-world setting, whether TUDCA had an impact on the overall survival of patients with ALS who were treated with this drug compared to those patients who received standard care only.

METHODS: This propensity score-matched study was conducted in the Emilia Romagna Region (Italy), which has had an ALS regional registry since 2009. Out of 627 patients with ALS diagnosed from January 1st, 2015 to June 30th, 2021 and recorded in the registry with available information on death/tracheostomy, 86 patients took TUDCA and were matched in a 1:2 ratio with patients who received only usual care according to age at onset, sex, phenotype, diagnostic latency, ALS Functional Rating Scale-Revised (ALSFRS-R) at first visit, disease progression rate at first visit, and BMI at diagnosis. The primary outcome was survival difference (time from onset of symptoms to tracheostomy/death) between TUDCA exposed and unexposed patients.

FINDINGS: A total of 86 patients treated with TUDCA were matched to 172 patients who did not receive treatment. TUDCA-exposed patients were stratified based on dosage (less than or equal to 1000 mg/day or greater) and duration (less than or equal to 12 months or longer) of treatment. The median overall survival was 49.6 months (95% CI 41.7-93.5) among those treated with TUDCA and 36.2 months (95% CI 32.7-41.6) in the control group, with a reduced risk of death observed in patients exposed to a higher dosage (defined as ≥ 1000 mg/day) of TUDCA (HR 0.56; 95% CI 0.38-0.83; p = 0.0042) compared to both the control group and those with lower TUDCA dosages (defined as < 1000 mg/day). TUDCA was generally well-tolerated, except for a minority of patients (n = 7, 8.1%) who discontinued treatment due to side effects, primarily gastrointestinal and mild in severity; only 2 adverse events required hospital access but resolved without sequelae.

INTERPRETATION: In this population-based exploratory study, patients with ALS who were treated with TUDCA may have prolonged survival compared to patients receiving standard care only. Additional prospective randomized studies are needed to confirm the efficacy and safety of this drug.

FUNDING: Emilia-Romagna Region.}, } @article {pmid37841873, year = {2023}, author = {Crone, N and Candrea, D and Shah, S and Luo, S and Angrick, M and Rabbani, Q and Coogan, C and Milsap, G and Nathan, K and Wester, B and Anderson, W and Rosenblatt, K and Clawson, L and Maragakis, N and Vansteensel, M and Tenore, F and Ramsey, N and Fifer, M and Uchil, A}, title = {A click-based electrocorticographic brain-computer interface enables long-term high-performance switch-scan spelling.}, journal = {Research square}, volume = {}, number = {}, pages = {}, pmid = {37841873}, issn = {2693-5015}, support = {T32 HD007414/HD/NICHD NIH HHS/United States ; UH3 NS114439/NS/NINDS NIH HHS/United States ; }, abstract = {BACKGROUND: Brain-computer interfaces (BCIs) can restore communication in movement- and/or speech-impaired individuals by enabling neural control of computer typing applications. Single command "click" decoders provide a basic yet highly functional capability.

METHODS: We sought to test the performance and long-term stability of click-decoding using a chronically implanted high density electrocorticographic (ECoG) BCI with coverage of the sensorimotor cortex in a human clinical trial participant (ClinicalTrials.gov, NCT03567213) with amyotrophic lateral sclerosis (ALS). We trained the participant's click decoder using a small amount of training data (< 44 minutes across four days) collected up to 21 days prior to BCI use, and then tested it over a period of 90 days without any retraining or updating.

RESULTS: Using this click decoder to navigate a switch-scanning spelling interface, the study participant was able to maintain a median spelling rate of 10.2 characters per min. Though a transient reduction in signal power modulation interrupted testing with this fixed model, a new click decoder achieved comparable performance despite being trained with even less data (< 15 min, within one day).

CONCLUSION: These results demonstrate that a click decoder can be trained with a small ECoG dataset while retaining robust performance for extended periods, providing functional text-based communication to BCI users.}, } @article {pmid37841575, year = {2023}, author = {Ayala, YM}, title = {Uncovering Critical Roles for RNA in Neurodegeneration.}, journal = {Missouri medicine}, volume = {120}, number = {5}, pages = {374-380}, pmid = {37841575}, issn = {0026-6620}, mesh = {Humans ; RNA/genetics ; *Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology ; DNA-Binding Proteins/genetics/metabolism ; *Frontotemporal Dementia/genetics/metabolism ; }, abstract = {RNA-binding proteins, in particular TDP-43, are key players in neurodegenerative disorders, mainly amyotrophic lateral sclerosis and frontotemporal dementia. We aim to elucidate how TDP-43 dysfunction alters cell metabolism and to identify mechanisms linked to aberrant behavior. We find that RNA binding plays a key role in maintaining TDP-43 homeostasis and in controlling cellular organization, two processes of essential importance to TDP-43 pathology. This research will provide insight into pathogenesis and help develop therapeutic interventions.}, } @article {pmid37840177, year = {2023}, author = {Li, XG and Liu, MS and Cui, LY}, title = {[Attention should be paid to the importance of genetic testing in clinical practice of amyotrophic lateral sclerosis].}, journal = {Zhonghua yi xue za zhi}, volume = {103}, number = {39}, pages = {3071-3076}, doi = {10.3760/cma.j.cn112137-20230516-00796}, pmid = {37840177}, issn = {0376-2491}, support = {81750002//National Natural Science Foundation of China/ ; 320675017092//the WJP Medical Foundation/ ; 2021I2MC&TA003//CAMS Innovation Fund for Medical Sciences (CIFMS)/ ; YJXJJZ2021001406//Beijing Yicheng Cooperative Development Foundation Research Project/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/genetics ; *Neurodegenerative Diseases/genetics/pathology ; Motor Neurons/pathology ; Superoxide Dismutase-1/genetics ; Genetic Testing ; Mutation ; Superoxide Dismutase/genetics ; }, abstract = {Amyotrophic lateral sclerosis(ALS) is a progressive and fatal neurodegenerative disease that mainly involves upper and lower motor neurons. It lacks clear biomarkers and can be clearly diagnosed only one and a half years after the onset. Gene test is of great significance for diagnosis, prognosis and genetic counseling. In recent years, several gene therapy studies have entered the clinical trial stage of ALS, among which the antisense oligonucleotide therapy targeting the pathogenic variation of the superoxide dismutase 1 (SOD1) gene has been launched, and it is urgent to carry out routine gene test in clinical practice. On the basis of progress of ALS gene research in recent years, family history, age of onset and typical clinical manifestations of patients are no longer considered as the basis for genetic testing. However, the target genes of clinical gene testing needs to be further clarified according to the diagnostic purpose, the testing method and scheme need to be standardized, and the genetic consultation before testing should be paid attention to, and the informed consent should be fully achieved.}, } @article {pmid37839397, year = {2023}, author = {Helwa, N and Sharma, M and Vanama, MS and Helwa, Y and El-Falou, A}, title = {Colonic Anastomotic Leak Model in Swine.}, journal = {European surgical research. Europaische chirurgische Forschung. Recherches chirurgicales europeennes}, volume = {64}, number = {4}, pages = {406-411}, doi = {10.1159/000534580}, pmid = {37839397}, issn = {1421-9921}, mesh = {Swine ; Animals ; *Anastomotic Leak/etiology ; *Colon/surgery ; Anastomosis, Surgical/adverse effects ; Postoperative Complications/etiology ; Models, Animal ; }, abstract = {INTRODUCTION: Anastomotic leaks (ALs) are serious postoperative complications. Current experimental studies designed to investigate leaks are based on acute intraoperative dehiscence of the anastomosis. Clinically, however, AL usually happens later in the postoperative course. Presented here is a clinically relevant colonic AL model in swine.

METHODS: Seventeen Yorkshire pigs were divided into 2 groups: the control group (n = 6) and the experimental group (n = 11). An enterotomy was performed on the descending colon and an end-to-end handsewn anastomosis was created in the groups. The proximal and distal ends of the suture were exteriorized and tied to a plastic tube. Subsequently, the suture was cut and pulled to induce breakdown of the anastomosis in the experimental group 3-4 h postoperatively. Study endpoints included behavioral changes, clinical assessment, laboratory indicators, and macroscopic indicators of leakage.

RESULTS: Leaks were successfully created in 8/11 of the experimental group animals and confirmed through exploratory relaparotomy. Seven of the experimental pigs showed complete anastomotic breakdown and one showed partial rupture. Fecal peritonitis and enteric spillage were observed macroscopically within the abdomen of the experimental pigs, confirming the presence of a leak. The remaining (3/11) experimental pigs did not experience those findings due to either a tamponade/containment by the abdominal wall or surrounding organs. Statistical significance (p < 0.05) was achieved between the experimental and control cohorts for laboratory and clinical indicators including fever, leukocytosis, and decreased blood potassium.

CONCLUSION: This animal model generated postoperative induced leak in approximately three-quarters (8/11) of experimental pigs, allowing control over the time of leak onset to simulate clinical settings.}, } @article {pmid37839080, year = {2024}, author = {Gaynor, LS and Yadollahikhales, G and Tsoy, E and Hall, M and Boxer, AL and Miller, BL and Grinberg, LT}, title = {C9orf72 Repeat Expansion Initially Presenting as Late-Onset Bipolar Disorder With Psychosis.}, journal = {The neurologist}, volume = {29}, number = {2}, pages = {109-112}, pmid = {37839080}, issn = {2331-2637}, support = {P50 AG023501/AG/NIA NIH HHS/United States ; K24 AG045333/AG/NIA NIH HHS/United States ; K24 AG053435/AG/NIA NIH HHS/United States ; R01 AG038791/AG/NIA NIH HHS/United States ; P01 AG019724/AG/NIA NIH HHS/United States ; U54 NS092089/NS/NINDS NIH HHS/United States ; T32 AG023481/AG/NIA NIH HHS/United States ; P30 AG062422/AG/NIA NIH HHS/United States ; }, mesh = {Female ; Humans ; Adult ; Middle Aged ; *Bipolar Disorder/diagnosis/genetics ; C9orf72 Protein/genetics ; *Frontotemporal Dementia/diagnosis/genetics ; *Psychotic Disorders/diagnosis/genetics ; *Apraxias ; }, abstract = {INTRODUCTION: C9orf72 expansion is the most common genetic abnormality in behavioral variant frontotemporal dementia (bvFTD) and amyotrophic lateral sclerosis. Although psychiatric prodromes are common in C9orf72 expansion carriers, there are only scattered reported cases of primary psychiatric disorders, such as bipolar disorder, diagnosed at disease onset. Moreover, C9orf72 carrier status is rarely identified in bipolar disorder genetic studies.

CASE REPORT: A 51-year-old, right-handed woman with 16 years of education presented for evaluation of long-standing cognitive and behavioral change. She initially displayed symptoms of mania and florid, multimodal psychotic symptoms at age 39. Her bipolar disorder symptoms were initially responsive to medication; however, she later developed executive dysfunction and behavioral symptoms consistent with bvFTD. She became progressively nonverbal, and her limited speech was notable for speech apraxia. At the time of presentation, she demonstrated cortical sensory deficit, ideomotor and oral-buccal apraxia, and unstable gait. Neuroimaging revealed diffuse brain atrophy. Postmortem histopathological evaluation revealed frontotemporal lobar degeneration with TDP-43 inclusions, type B, and genetic study identified C9orf72 expansion. A detailed review of family history found a strong paternal history of bipolar disorder and substance use disorder.

CONCLUSIONS: We describe a rare case of C9orf72 expansion initially characterized by late-onset bipolar disorder and florid, multimodal psychotic symptoms, followed years later by bvFTD diagnosis. This report emphasizes the importance of completing a neurological examination, obtaining a detailed family history, and pursuing genetic screening to distinguish between primary psychiatric disorder and bvFTD in individuals who meet the criteria for late-onset bipolar disorder.}, } @article {pmid37838979, year = {2024}, author = {Jagadish, A and Shankaranarayana, AM and Natarajan, M and Solomon, JM}, title = {Transcranial direct current stimulation for fatigue in neurological conditions: A systematic scoping review.}, journal = {Physiotherapy research international : the journal for researchers and clinicians in physical therapy}, volume = {29}, number = {1}, pages = {e2054}, doi = {10.1002/pri.2054}, pmid = {37838979}, issn = {1471-2865}, mesh = {Humans ; *Brain Injuries, Traumatic ; Fatigue/therapy/etiology ; *Multiple Sclerosis/complications/therapy ; *Parkinson Disease ; Quality of Life ; *Stroke ; *Transcranial Direct Current Stimulation/adverse effects ; }, abstract = {BACKGROUND AND PURPOSE: Fatigue following neurological conditions negatively impacts daily activities, reducing overall quality of life. Transcranial direct current stimulation (tDCS) for fatigue management is still underexplored. This scoping review explores its use in managing fatigue among various neurological conditions.

METHODS: A thorough literature search was carried out using PubMed, Scopus, CINAHL, Web of Science, Embase, ProQuest, and the Cochrane Library. Google Scholar and clinicaltrials.gov were manually searched for gray literature and ongoing trials, respectively. Regardless of the study design, all studies utilizing tDCS for the management of fatigue in various neurological conditions were considered. Two reviewers independently screened all the studies, following which the data were retrieved.

RESULTS: Studies employing tDCS for fatigue management across neurological conditions is as follows: Multiple sclerosis (MS) (n = 28, 66%), stroke (n = 5, 12%), Parkinson's disease (PD) (n = 4, 10%), post-polio syndrome (PPS) (n = 2, 5%), traumatic brain injury (TBI) (n = 2, 5%), and amyotrophic lateral sclerosis (n = 1, 2%). All the studies used anodal stimulation, with the common stimulation site being the left dorsolateral prefrontal cortex for MS, stroke, and PD. A stimulation intensity of 1.0-4.0 mA with a duration ranging from 15 to 30 min in 1 to 24 sessions were commonly reported. The Fatigue Severity Scale (n = 21) and Modified Fatigue Impact Scale (n = 17) were frequently implemented outcome measures. Regardless of the study design, 36/42 (85.7%) studies reported an improvement in fatigue scores in the tDCS group. The common adverse events noted were tingling (n = 8, 35%), headache (n = 6, 26%), and itching (n = 6, 26%).

DISCUSSION: Application of tDCS for fatigue was explored in individuals with stroke, PD, PPS, and TBI after MS. Even though a wide range of treatment parameters and outcome measures were adopted to assess and target fatigue, tDCS proves to have a promising role in alleviating this symptom.}, } @article {pmid37838698, year = {2023}, author = {Zeballos C, MA and Moore, HJ and Smith, TJ and Powell, JE and Ahsan, NS and Zhang, S and Gaj, T}, title = {Mitigating a TDP-43 proteinopathy by targeting ataxin-2 using RNA-targeting CRISPR effector proteins.}, journal = {Nature communications}, volume = {14}, number = {1}, pages = {6492}, pmid = {37838698}, issn = {2041-1723}, support = {R01 GM141296/GM/NIGMS NIH HHS/United States ; T32 EB019944/EB/NIBIB NIH HHS/United States ; U01 NS122102/NS/NINDS NIH HHS/United States ; R01 NS123556/NS/NINDS NIH HHS/United States ; }, mesh = {Mice ; Animals ; Ataxin-2/genetics ; RNA/metabolism ; *TDP-43 Proteinopathies/genetics/metabolism/pathology ; *Amyotrophic Lateral Sclerosis/genetics ; DNA-Binding Proteins/genetics/metabolism ; }, abstract = {The TDP-43 proteinopathies, which include amyotrophic lateral sclerosis and frontotemporal dementia, are a devastating group of neurodegenerative disorders that are characterized by the mislocalization and aggregation of TDP-43. Here we demonstrate that RNA-targeting CRISPR effector proteins, a programmable class of gene silencing agents that includes the Cas13 family of enzymes and Cas7-11, can be used to mitigate TDP-43 pathology when programmed to target ataxin-2, a modifier of TDP-43-associated toxicity. In addition to inhibiting the aggregation and transit of TDP-43 to stress granules, we find that the in vivo delivery of an ataxin-2-targeting Cas13 system to a mouse model of TDP-43 proteinopathy improved functional deficits, extended survival, and reduced the severity of neuropathological hallmarks. Further, we benchmark RNA-targeting CRISPR platforms against ataxin-2 and find that high-fidelity forms of Cas13 possess improved transcriptome-wide specificity compared to Cas7-11 and a first-generation effector. Our results demonstrate the potential of CRISPR technology for TDP-43 proteinopathies.}, } @article {pmid37838538, year = {2024}, author = {Wang, SA and Lee, HW and Ko, YC and Sun, JT and Matsuyama, T and Lin, CH and Hsieh, MJ and Chiang, WC and Ma, MH}, title = {Effect of crew ratio of advanced life support-trained personnel on patients with out-of-hospital cardiac arrest: A systematic review and meta-analysis.}, journal = {Journal of the Formosan Medical Association = Taiwan yi zhi}, volume = {123}, number = {5}, pages = {561-570}, doi = {10.1016/j.jfma.2023.10.008}, pmid = {37838538}, issn = {0929-6646}, mesh = {Humans ; *Out-of-Hospital Cardiac Arrest/therapy/mortality ; *Emergency Medical Services ; *Advanced Cardiac Life Support ; Cardiopulmonary Resuscitation ; Taiwan ; Return of Spontaneous Circulation ; Japan ; }, abstract = {BACKGROUND/PURPOSE: This review aimed to investigate the effect of crew ratios of on-scene advanced life support (ALS)-trained personnel on patients with out-of-hospital cardiac arrest (OHCA).

METHODS: We systematically searched PubMed, Ovid EMBASE, and the Cochrane Central Register of Controlled Trials databases from the inception date until September 30, 2022, for eligible studies. Two reviewers independently screened the studies for relevance, extracted data, and quality. We compared the effect of the ratio of on-scene ALS-trained personnel >50 % to those with a ratio ≤50 % among prehospital personnel on the clinical outcomes of OHCA patients. The primary outcome was survival-to-discharge and secondary outcomes were any return of spontaneous circulation (ROSC), sustained ROSC (≥2 h), and favourable neurological outcome at discharge (cerebral performance category scores: 1 or 2). Pooled odds ratios (ORs) were calculated, and the certainty of evidence was assessed.

RESULTS: From 10,864 references, we identified four non-randomised studies, including 16,475 patients. Two studies were performed in Japan and two in Taiwan. There were significant differences in survival-to-discharge (OR: 1.24, 95 % confidence interval [CI]: 1.07-1.44, I[2]: 7 %), any ROSC (OR:1.22, 95 % CI: 1.04-1.43, I[2]: 74 %) and sustained ROSC (OR: 1.39, 95 % CI: 1.16-1.65, I[2]: 40 %), but insignificant differences in favourable neurological outcome at discharge. The overall certainty of evidence was rated as very low for all outcomes.

CONCLUSION: Prehospital ALS care with a ratio of on-scene ALS-trained personnel >50 % could improve OHCA patient outcomes than crew ratios ≤50 %. Further studies are required to reach a robust conclusion.}, } @article {pmid37838312, year = {2023}, author = {Kumar, R and Malik, MZ and Thanaraj, TA and Bagabir, SA and Haque, S and Tambuwala, M and Haider, S}, title = {A computational biology approach to identify potential protein biomarkers and drug targets for sporadic amyotrophic lateral sclerosis.}, journal = {Cellular signalling}, volume = {112}, number = {}, pages = {110915}, doi = {10.1016/j.cellsig.2023.110915}, pmid = {37838312}, issn = {1873-3913}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy/genetics/metabolism ; *Neurodegenerative Diseases ; Molecular Docking Simulation ; Proteins ; Computational Biology ; Biomarkers ; *Cyclosporins/therapeutic use ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease caused by the loss of upper and lower motor neurons. The sporadic ALS (sALS) is a multigenic disorder and the complex mechanisms underlying its onset are still not fully delineated. Despite the recent scientific advancements, certain aspects of ALS pathogenic targets need to be yet clarified. The aim of the presented study is to identify potential genetic biomarkers and drug targets for sALS, by analysing gene expression profiles, presented in the publicly available GSE68605 dataset, of motor neurons cells obtained from sALS patients. We used different computational approaches including differential expression analysis, protein network mapping, candidate protein biomarker (CPB) identification, elucidation of the role of functional modules, and molecular docking analysis. The resultant top ten up- and downregulated genes were further used to construct protein-protein interaction network (PPIN). The PPIN analysis resulted in identifying four CPBs (namely RIOK2, AKT1, CTNNB1, and TNF) that commonly overlapped with one another in network parameters (degree, bottleneck and maximum neighbourhood component). The RIOK2 protein emerged as a potential mediator of top five functional modules that are associated with RNA binding, lipoprotein particle receptor binding in pre-ribosome, and interferon, cytokine-mediated signaling pathway. Furthermore, molecular docking analysis revealed that cyclosporine exhibited the highest binding affinity (-8.6 kJ/mol) with RIOK2, and surpassed the FDA-approved ALS drugs, such as riluzole and edaravone. This suggested that cyclosporine may serve as a promising candidate for targeting RIOK2 downregulation observed in sALS patients. In order to validate our computational results, it is suggested that in vitro and in vivo studies may be conducted in future to provide a more detailed understanding of ALS diagnosis, prognosis, and therapeutic intervention.}, } @article {pmid37837507, year = {2024}, author = {Hamad, AA and Amer, BE and Abbas, NB and Alnajjar, AZ and Meshref, M}, title = {Prevalence and correlates of fatigue in amyotrophic lateral sclerosis: A systematic review and meta-analysis.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {45}, number = {2}, pages = {485-493}, pmid = {37837507}, issn = {1590-3478}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/complications/epidemiology ; Prevalence ; Quality of Life ; Fatigue/etiology/complications ; }, abstract = {OBJECTIVES: This systematic review and meta-analysis aimed to determine the frequency and correlates of fatigue in patients with amyotrophic lateral sclerosis (ALS).

METHODS: Three databases were searched up to 2nd May 2023 to identify studies reporting fatigue frequency in ALS. Studies included had to identify ALS patients through one of ALS diagnostic criteria and measure fatigue by a validated tool with a specific cut-off value. Meta-analysis was conducted using RStudio's "meta" package with a random-effects model. Subgroup analyses and meta-regression explored the relationship between fatigue frequency in ALS and different covariates.

RESULTS: Eleven studies, compromising 1072 patients, met the inclusion criteria and were included in our analysis. The pooled frequency of fatigue across all studies was 48% (95% CI = 40% to 57%). Our subgroup analysis based on the ALSFRS-R revealed a higher frequency of fatigue in studies with lower scores (< 30) compared to those with higher scores (≥ 30), with a pooled frequency of 62% (95% CI = 43% to 79%) and 43% (95% CI = 37% to 49%), respectively. Also, the meta-regression analysis showed a significant negative association between fatigue and ALSFRS-R mean (P = 0.02). The included studies reported an association between fatigue and lower functional status and poorer quality of life in patients with ALS.

CONCLUSION: Our findings suggest that fatigue is prevalent in almost half of ALS patients and is associated with lower functional status and poorer quality of life, highlighting the importance of assessing and managing fatigue in ALS patients.}, } @article {pmid37836771, year = {2023}, author = {Colombo, E and Olla, S and Minnelli, C and Formato, A and Veroni, C and Corbisiero, S and Pericolo, M and Siguri, C and Mobbili, G and Agresti, C and Seneci, P}, title = {Synthesis and Characterization of Edaravone Analogues as Remyelinating Agents and Putative Mechanistic Probes.}, journal = {Molecules (Basel, Switzerland)}, volume = {28}, number = {19}, pages = {}, pmid = {37836771}, issn = {1420-3049}, support = {2017/R/2//Fondazione Italiana Sclerosi Multipla/ ; }, mesh = {Humans ; Edaravone/pharmacology/therapeutic use ; *Antioxidants/pharmacology/therapeutic use ; *Amyotrophic Lateral Sclerosis/drug therapy ; Oxidative Stress ; Esters/pharmacology ; }, abstract = {Edaravone (EDA), an antioxidant drug approved for the treatment of ischemic stroke and amyotrophic lateral sclerosis, was recently proposed as a remyelinating candidate for the treatment of multiple sclerosis. Here, we synthesized twelve EDA analogues 2b-4c showing three substitution patterns A-C, searching for improved remyelinating agents and putative molecular targets responsible for their regenerative activity. We profiled them in three primary assays to determine their stimulation of oligodendrocyte progenitor cell metabolism (tetrazolium MTT assay), their antioxidant potential (2,2-diphenyl-1-picrylhydrazyl-DPPH assay) and to predict their bioavailability (virtual ADME profile). Active 4'-carboxylate 2b, 4'-ester 2c and N[1]-carbamate-4'-ester 4a were further characterized, justifying their in vitro effects and selecting 4a as a putative EDA 1 prodrug suitable for in vivo testing.}, } @article {pmid37834458, year = {2023}, author = {Shvetcov, A and Thomson, S and Spathos, J and Cho, AN and Wilkins, HM and Andrews, SJ and Delerue, F and Couttas, TA and Issar, JK and Isik, F and Kaur, S and Drummond, E and Dobson-Stone, C and Duffy, SL and Rogers, NM and Catchpoole, D and Gold, WA and Swerdlow, RH and Brown, DA and Finney, CA}, title = {Blood-Based Transcriptomic Biomarkers Are Predictive of Neurodegeneration Rather Than Alzheimer's Disease.}, journal = {International journal of molecular sciences}, volume = {24}, number = {19}, pages = {}, pmid = {37834458}, issn = {1422-0067}, support = {P01 AG060882/AG/NIA NIH HHS/United States ; }, mesh = {Humans ; *Alzheimer Disease/diagnosis/genetics/metabolism ; *Neurodegenerative Diseases ; *Amyotrophic Lateral Sclerosis/diagnosis/genetics/metabolism ; Transcriptome ; *Parkinson Disease/diagnosis/genetics/metabolism ; Biomarkers/metabolism ; }, abstract = {Alzheimer's disease (AD) is a growing global health crisis affecting millions and incurring substantial economic costs. However, clinical diagnosis remains challenging, with misdiagnoses and underdiagnoses being prevalent. There is an increased focus on putative, blood-based biomarkers that may be useful for the diagnosis as well as early detection of AD. In the present study, we used an unbiased combination of machine learning and functional network analyses to identify blood gene biomarker candidates in AD. Using supervised machine learning, we also determined whether these candidates were indeed unique to AD or whether they were indicative of other neurodegenerative diseases, such as Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS). Our analyses showed that genes involved in spliceosome assembly, RNA binding, transcription, protein synthesis, mitoribosomes, and NADH dehydrogenase were the best-performing genes for identifying AD patients relative to cognitively healthy controls. This transcriptomic signature, however, was not unique to AD, and subsequent machine learning showed that this signature could also predict PD and ALS relative to controls without neurodegenerative disease. Combined, our results suggest that mRNA from whole blood can indeed be used to screen for patients with neurodegeneration but may be less effective in diagnosing the specific neurodegenerative disease.}, } @article {pmid37834407, year = {2023}, author = {Baj, J and Flieger, W and Barbachowska, A and Kowalska, B and Flieger, M and Forma, A and Teresiński, G and Portincasa, P and Buszewicz, G and Radzikowska-Büchner, E and Flieger, J}, title = {Consequences of Disturbing Manganese Homeostasis.}, journal = {International journal of molecular sciences}, volume = {24}, number = {19}, pages = {}, pmid = {37834407}, issn = {1422-0067}, mesh = {Humans ; Manganese/toxicity/metabolism ; *Diabetes Mellitus, Type 2 ; *Manganese Poisoning/metabolism ; Homeostasis ; *Neurodegenerative Diseases ; }, abstract = {Manganese (Mn) is an essential trace element with unique functions in the body; it acts as a cofactor for many enzymes involved in energy metabolism, the endogenous antioxidant enzyme systems, neurotransmitter production, and the regulation of reproductive hormones. However, overexposure to Mn is toxic, particularly to the central nervous system (CNS) due to it causing the progressive destruction of nerve cells. Exposure to manganese is widespread and occurs by inhalation, ingestion, or dermal contact. Associations have been observed between Mn accumulation and neurodegenerative diseases such as manganism, Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. People with genetic diseases associated with a mutation in the gene associated with impaired Mn excretion, kidney disease, iron deficiency, or a vegetarian diet are at particular risk of excessive exposure to Mn. This review has collected data on the current knowledge of the source of Mn exposure, the experimental data supporting the dispersive accumulation of Mn in the brain, the controversies surrounding the reference values of biomarkers related to Mn status in different matrices, and the competitiveness of Mn with other metals, such as iron (Fe), magnesium (Mg), zinc (Zn), copper (Cu), lead (Pb), calcium (Ca). The disturbed homeostasis of Mn in the body has been connected with susceptibility to neurodegenerative diseases, fertility, and infectious diseases. The current evidence on the involvement of Mn in metabolic diseases, such as type 2 diabetes mellitus/insulin resistance, osteoporosis, obesity, atherosclerosis, and non-alcoholic fatty liver disease, was collected and discussed.}, } @article {pmid37834374, year = {2023}, author = {Oprisan, AL and Popescu, BO}, title = {Dysautonomia in Amyotrophic Lateral Sclerosis.}, journal = {International journal of molecular sciences}, volume = {24}, number = {19}, pages = {}, pmid = {37834374}, issn = {1422-0067}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/pathology ; *Neurodegenerative Diseases/pathology ; Motor Neurons/pathology ; *Primary Dysautonomias/etiology/pathology ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease, characterized in its typical presentation by a combination of lower and upper motor neuron symptoms, with a progressive course and fatal outcome. Due to increased recognition of the non-motor symptoms, it is currently considered a multisystem disorder with great heterogeneity, regarding genetical, clinical, and neuropathological features. Often underestimated, autonomic signs and symptoms have been described in patients with ALS, and various method analyses have been used to assess autonomic nervous system involvement. The aim of this paper is to offer a narrative literature review on autonomic disturbances in ALS, based on the scarce data available to date.}, } @article {pmid37834128, year = {2023}, author = {Huber, K and Szerenos, E and Lewandowski, D and Toczylowski, K and Sulik, A}, title = {The Role of Adipokines in the Pathologies of the Central Nervous System.}, journal = {International journal of molecular sciences}, volume = {24}, number = {19}, pages = {}, pmid = {37834128}, issn = {1422-0067}, mesh = {Humans ; Adipokines/metabolism ; Central Nervous System/metabolism ; *Alzheimer Disease/metabolism ; *Amyotrophic Lateral Sclerosis/metabolism ; Adipose Tissue/metabolism ; }, abstract = {Adipokines are protein hormones secreted by adipose tissue in response to disruptions in physiological homeostasis within the body's systems. The regulatory functions of adipokines within the central nervous system (CNS) are multifaceted and intricate, and they have been identified in a number of pathologies. Therefore, specific adipokines have the potential to be used as biomarkers for screening purposes in neurological dysfunctions. The systematic review presented herein focuses on the analysis of the functions of various adipokines in the pathogenesis of CNS diseases. Thirteen proteins were selected for analysis through scientific databases. It was found that these proteins can be identified within the cerebrospinal fluid either by their ability to modify their molecular complex and cross the blood-brain barrier or by being endogenously produced within the CNS itself. As a result, this can correlate with their measurability during pathological processes, including Alzheimer's disease, amyotrophic lateral sclerosis, multiple sclerosis, depression, or brain tumors.}, } @article {pmid37834094, year = {2023}, author = {Jellinger, KA}, title = {The Spectrum of Cognitive Dysfunction in Amyotrophic Lateral Sclerosis: An Update.}, journal = {International journal of molecular sciences}, volume = {24}, number = {19}, pages = {}, pmid = {37834094}, issn = {1422-0067}, support = {000//Society for the Promotion of Research in Experimental Neurology, Vienna, Austria/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics ; *Frontotemporal Dementia/genetics ; Brain/pathology ; *Cognition Disorders/pathology ; *Cognitive Dysfunction/pathology ; *Neurodegenerative Diseases/pathology ; *Pick Disease of the Brain/pathology ; }, abstract = {Cognitive dysfunction is an important non-motor symptom in amyotrophic lateral sclerosis (ALS) that has a negative impact on survival and caregiver burden. It shows a wide spectrum ranging from subjective cognitive decline to frontotemporal dementia (FTD) and covers various cognitive domains, mainly executive/attention, language and verbal memory deficits. The frequency of cognitive impairment across the different ALS phenotypes ranges from 30% to 75%, with up to 45% fulfilling the criteria of FTD. Significant genetic, clinical, and pathological heterogeneity reflects deficits in various cognitive domains. Modern neuroimaging studies revealed frontotemporal degeneration and widespread involvement of limbic and white matter systems, with hypometabolism of the relevant areas. Morphological substrates are frontotemporal and hippocampal atrophy with synaptic loss, associated with TDP-43 and other co-pathologies, including tau deposition. Widespread functional disruptions of motor and extramotor networks, as well as of frontoparietal, frontostriatal and other connectivities, are markers for cognitive deficits in ALS. Cognitive reserve may moderate the effect of brain damage but is not protective against cognitive decline. The natural history of cognitive dysfunction in ALS and its relationship to FTD are not fully understood, although there is an overlap between the ALS variants and ALS-related frontotemporal syndromes, suggesting a differential vulnerability of motor and non-motor networks. An assessment of risks or the early detection of brain connectivity signatures before structural changes may be helpful in investigating the pathophysiological mechanisms of cognitive impairment in ALS, which might even serve as novel targets for effective disease-modifying therapies.}, } @article {pmid37833071, year = {2023}, author = {}, title = {Erratum: Huh et al., "Time Course of Alterations in Adult Spinal Motoneuron Properties in the SOD1(G93A) Mouse Model of ALS".}, journal = {eNeuro}, volume = {10}, number = {10}, pages = {}, doi = {10.1523/ENEURO.0370-23.2023}, pmid = {37833071}, issn = {2373-2822}, } @article {pmid37833013, year = {2023}, author = {Bryukhovetskiy, AS and Grivtsova, LY and Bogachev, SS and Ustyugov, AA and Nebogatikov, VO and Shurdov, MA}, title = {Technology of genomic balancing of chromatin of autologous hematopoietic stem cells for gene therapy of fatal immune-mediated diseases of civilization, extended life expectancy and sudden human death prevention.}, journal = {International review of neurobiology}, volume = {172}, number = {}, pages = {237-284}, doi = {10.1016/bs.irn.2023.07.005}, pmid = {37833013}, issn = {2162-5514}, mesh = {Rats ; Humans ; Animals ; Mice ; *Chromatin/metabolism ; *Quality of Life ; Rats, Wistar ; Hematopoietic Stem Cells/metabolism ; Genetic Therapy ; Life Expectancy ; Genomics ; DNA/metabolism ; Technology ; Death, Sudden ; Civilization ; }, abstract = {A biotechnology for personalized ex vivo gene therapy based on molecular genomic balancing of hematopoietic stem cell (HSC) chromatin with nucleosome monomers of human genomic DNA (hDNA[nmr]) has been developed and implemented in the clinic to change (to "correct") mutant chromosome loci genomes of dominant HSC clones that form mono- and oligoclonal hematopoiesis during aging and major (oncological, cardiovascular, neurodegenerative and autoimmune) fatal immune-mediated diseases of civilization. A fundamentally new biotechnological approach has been applied to the delivery of genetic material into eukaryotic stem and progenitor cells by establishing an artificial "recombinogenic situation" in them to induce homologous recombination (equivalent replacement) of mutant DNA regions with healthy hDNA[nmr]. In experimental preclinical trials, the effectiveness of genomic balancing technology has been proven to reduce the risk of sudden death in old animals and to increase the lifespan of outbred mice by 30% and Wistar rats by 57%. The improvement in their quality of life, compared with the control, is explained by an increase in the telomeric regions of the HSCs and HPCs chromosomes by 1.5-2 times. The potential of the technology to slow down the hereditary neurodegenerative diseases on the model of amyotrophic lateral sclerosis is shown. The effectiveness of this technology in clinical practice is presented on the example of a terminal patient with stage 4 neuroendocrine cancer. This technology used in the treatment of a number of oncological, neurodegenerative, autoimmune and hereditary diseases with clonal hematopoiesis is able to arrest the progression of the disease, prevent its recurrence, prolong the active life of a person, increase the average life expectancy and prevent sudden death.}, } @article {pmid37832609, year = {2023}, author = {Rezaee, D and Saadatpour, F and Akbari, N and Zoghi, A and Najafi, S and Beyranvand, P and Zamani-Rarani, F and Rashidi, MA and Bagheri-Mohammadi, S and Bakhtiari, M}, title = {The role of microRNAs in the pathophysiology of human central nervous system: A focus on neurodegenerative diseases.}, journal = {Ageing research reviews}, volume = {92}, number = {}, pages = {102090}, doi = {10.1016/j.arr.2023.102090}, pmid = {37832609}, issn = {1872-9649}, mesh = {Humans ; *MicroRNAs/genetics/metabolism ; *Neurodegenerative Diseases/metabolism ; Amyloid beta-Peptides ; *Alzheimer Disease/genetics/metabolism ; Central Nervous System/metabolism ; *Neoplasms ; }, abstract = {microRNAs (miRNAs) are suggested to play substantial roles in regulating the development and various physiologic functions of the central nervous system (CNS). These include neurogenesis, cell fate and differentiation, morphogenesis, formation of dendrites, and targeting non-neural mRNAs. Notably, deregulation of an increasing number of miRNAs is associated with several neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, multiple sclerosis, amyotrophic lateral sclerosis and CNS tumors. They are particularly known to affect the amyloid β (Aβ) cleavage and accumulation, tau protein homeostasis, and expression of alpha-synuclein (α-syn), Parkin, PINK1, and brain-derived neurotrophic factor (BDNF) that play pivotal roles in the pathogenesis of neurodegenerative diseases. These include miR-16, miR-17-5p, miR-20a, miR-106a, miR-106b, miR-15a, miR-15b, miR-103, miR-107, miR-298, miR-328, miR-195, miR-485, and miR-29. In CNS tumors, several miRNAs, including miR-31, miR-16, and miR-21 have been identified to modulate tumorigenesis through impacting tumor invasion and apoptosis. In this review article, we have a look at the recent advances on our knowledge about the role of miRNAs in human brain development and functions, neurodegenerative diseases, and their clinical potentials.}, } @article {pmid37832429, year = {2023}, author = {Migliorelli, L and Scoppolini Massini, L and Coccia, M and Villani, L and Frontoni, E and Squartini, S}, title = {A deep learning-based telemonitoring application to automatically assess oral diadochokinesis in patients with bulbar amyotrophic lateral sclerosis.}, journal = {Computer methods and programs in biomedicine}, volume = {242}, number = {}, pages = {107840}, doi = {10.1016/j.cmpb.2023.107840}, pmid = {37832429}, issn = {1872-7565}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis ; *Deep Learning ; Software ; }, abstract = {BACKGROUND AND OBJECTIVES: Timely identification of dysarthria progression in patients with bulbar-onset amyotrophic lateral sclerosis (ALS) is relevant to have a comprehensive assessment of the disease evolution. To this goal literature recognized the utmost importance of the assessment of the number of syllables uttered by a subject during the oral diadochokinesis (DDK) test.

METHODS: To support clinicians, this work proposes a remote deep learning-based system, which consists (i) of a web application to acquire audio tracks of bulbar-onset ALS patients and healthy control subjects while performing the oral DDK test (i.e., repeating the /pa/, /pa-ta-ka/ and /oo-ee/ syllables) and (ii) a DDK-AID network designed to process the acquired audio signals which have different duration and to output the number of per-task syllables repeated by the subject.

RESULTS: The DDK-AID network overcomes the comparative method achieving a mean Accuracy of 90.23 in counting syllables repeated by the eleven bulbar-onset ALS-patients while performing the oral DDK test.

CONCLUSIONS: The proposed remote monitoring system, in the light of the achieved performance, represents an important step towards the implementation of self-service telemedicine systems which may ensure customised care plans.}, } @article {pmid37832380, year = {2023}, author = {Kwon, S and Kim, B and Han, KD and Jung, W and Cho, EB and Yang, JH and Shin, DW and Min, JH}, title = {Increased risk of myocardial infarction in amyotrophic lateral sclerosis: A nationwide cohort study in South Korea.}, journal = {Journal of the neurological sciences}, volume = {454}, number = {}, pages = {120829}, doi = {10.1016/j.jns.2023.120829}, pmid = {37832380}, issn = {1878-5883}, mesh = {Humans ; Male ; Female ; Cohort Studies ; *Amyotrophic Lateral Sclerosis/epidemiology ; *Myocardial Infarction/epidemiology ; Obesity ; Incidence ; }, abstract = {BACKGROUND: The risk of myocardial infarction (MI), the major form of CVD, in amyotrophic lateral sclerosis (ALS) is currently unknown. We investigated the risk of MI in ALS and analyzed the effect of ALS-related physical disability on the risk of MI using the Korean National Health Insurance Service database.

METHODS: A total of 659 ALS patients and 10,927 non-ALS participants were finally selected between January 1, 2011, and December 31, 2015. A Cox hazard regression model was used to examine the hazard ratios (HRs) for MI in ALS after adjustment for potential confounders.

RESULTS: The incidence rate of MI was 26.2 per 1000 person-years, and the adjusted HR (aHR) for MI in ALS patients was 10.6 (95% confidence interval [CI] 7.2-15.4) compared with the controls. ALS patients who developed physical disability had an even higher risk of MI (aHR 18.6, 95% CI 11.5-30.0) compared with those who did not develop disability (aHR 7.4, 95% CI 4.6-11.9). The increased risk of MI was more prominent in female subjects than in male subjects (aHR 17.8, 95% CI 10.8-29.4 vs. aHR 6.9, 95% CI 4.1-11.6, P for interaction 0.006) and in obese subjects than in non-obese subjects (aHR 17.8, 95% CI 10.5-30.1 vs. aHR 7.9, 95% CI 4.9-12.8, P for interaction 0.018).

CONCLUSIONS: Our findings suggest that the risk of MI is high in ALS patients compared with a control population, and the risk is more prominent in those who develop physical disability, or who are female or obese.}, } @article {pmid37831677, year = {2023}, author = {Kim, JA and Jang, H and Choi, Y and Min, YG and Hong, YH and Sung, JJ and Choi, SJ}, title = {Subclinical articulatory changes of vowel parameters in Korean amyotrophic lateral sclerosis patients with perceptually normal voices.}, journal = {PloS one}, volume = {18}, number = {10}, pages = {e0292460}, pmid = {37831677}, issn = {1932-6203}, mesh = {Humans ; *Dysarthria/diagnosis/etiology ; *Amyotrophic Lateral Sclerosis ; Speech Intelligibility ; Phonetics ; Republic of Korea ; Speech Acoustics ; }, abstract = {The available quantitative methods for evaluating bulbar dysfunction in patients with amyotrophic lateral sclerosis (ALS) are limited. We aimed to characterize vowel properties in Korean ALS patients, investigate associations between vowel parameters and clinical features of ALS, and analyze subclinical articulatory changes of vowel parameters in those with perceptually normal voices. Forty-three patients with ALS (27 with dysarthria and 16 without dysarthria) and 20 healthy controls were prospectively collected in the study. Dysarthria was assessed using the ALS Functional Rating Scale-Revised (ALSFRS-R) speech subscores, with any loss of 4 points indicating the presence of dysarthria. The structured speech samples were recorded and analyzed using Praat software. For three corner vowels (/a/, /i/, and /u/), data on the vowel duration, fundamental frequency, frequencies of the first two formants (F1 and F2), harmonics-to-noise ratio, vowel space area (VSA), and vowel articulation index (VAI) were extracted from the speech samples. Corner vowel durations were significantly longer in ALS patients with dysarthria than in healthy controls. The F1 frequency of /a/, F2 frequencies of /i/ and /u/, the VSA, and the VAI showed significant differences between ALS patients with dysarthria and healthy controls. The area under the curve (AUC) was 0.912. The F1 frequency of /a/ and the VSA were the major determinants for differentiating ALS patients who had not yet developed apparent dysarthria from healthy controls (AUC 0.887). In linear regression analyses, as the ALSFRS-R speech subscore decreased, both the VSA and VAI were reduced. In contrast, vowel durations were found to be rather prolonged. The analyses of vowel parameters provided a useful metric correlated with disease severity for detecting subclinical bulbar dysfunction in ALS patients.}, } @article {pmid37831552, year = {2023}, author = {Trabelsi, T and Esposito, VJ and Francisco, JS}, title = {Spectroscopy and Photochemistry of Aluminum-Bearing Species in the Universe.}, journal = {Accounts of chemical research}, volume = {56}, number = {21}, pages = {3045-3052}, doi = {10.1021/acs.accounts.3c00481}, pmid = {37831552}, issn = {1520-4898}, abstract = {ConspectusMetal-bearing molecules impact the chemical and physical environment of many astronomical sources such as the circumstellar envelopes of large asymptotic giant branch and red supergiant stars, the interstellar medium, and planetary atmospheres (e.g., ablation of ∼20 tons per day into the Earth's upper atmosphere). In recent decades, the number of successfully detected metal-containing molecules has increased via rotational spectroscopic observations, which are driven by theoretical and experimental investigations. Following formation, the ultimate fate of each species (stabilization, dissociation, etc.) is determined by its electronic structure and electronic spectroscopic properties as it encounters the pervasive radiation fields in the vacuum of space. Studying these properties can evince the possibility of detection and predict the impact each molecule has on its surrounding environment. Aluminum, one of the most abundant elements and metals, is distributed throughout the universe as a constituent of gas-phase molecules (e.g., AlO, AlOH, AlCl, etc.) as well as condensed onto solid dust grains such as Al2O3. Free gas-phase aluminum-bearing molecules are synthesized by nonthermal equilibrium processes such as shocks and pulsations near the stellar photosphere or via the reaction of molecules on the surface of dust grains. Recent investigations in our research group utilizing quantum chemical methods, such as coupled cluster (CCSD(T) and CCSD(T)-F12) and multireference configuration interaction (MRCI) with large basis sets, have explored a wide breadth of spectroscopy and photochemistry of small (triatomic and tetratomic) aluminum-bearing molecules, including Al-H, Al-C, Al-N, Al-O, Al-Si, Al-P, and Al-S bonds, among others. The ground-state spectroscopy (rotational and vibrational) of various aluminum-bearing molecules is discussed in the context of experimental and observational detection potentials. These detection potentials depend on various factors, such as the magnitude of the permanent dipole moment (PDM) and the population of states yielding transition frequencies in detectable ranges. Many aluminum-bearing molecules possess large PDMs and may be prime candidates for astronomical and laboratory detection. Within this discussion, interesting aspects of the ground-state molecular orbital configuration of OAlNO are shown to lead to an uncommon triplet ground state. Additionally, the electronic absorption spectrum of the quasi-isoenergetic ground-state isomers of AlOSO is discussed as a sensitive method for detecting this species and differentiating between the two isomers. Finally, photochemical mechanisms key to the production of AlO and AlOH in low-density regions and the destruction of AlCO and AlOC are also discussed in order to understand the radiation-induced formation and destruction of these molecules.}, } @article {pmid37831200, year = {2023}, author = {Latorre-Rodríguez, AR and Huang, J and Schaheen, L and Smith, MA and Hashimi, S and Bremner, RM and Mittal, SK}, title = {Diagnosis and management of anastomotic leaks after Ivor Lewis esophagectomy: a single-center experience.}, journal = {Langenbeck's archives of surgery}, volume = {408}, number = {1}, pages = {397}, pmid = {37831200}, issn = {1435-2451}, mesh = {Humans ; *Anastomotic Leak/diagnosis/etiology/therapy ; Esophagectomy/adverse effects ; *Esophageal Neoplasms/surgery ; Endoscopy, Gastrointestinal/adverse effects ; Retrospective Studies ; Postoperative Complications/diagnosis/epidemiology/etiology ; Anastomosis, Surgical/adverse effects ; Treatment Outcome ; }, abstract = {PURPOSE: Esophageal anastomotic leaks (ALs) after esophagectomy are a common and serious complication. The incidence, diagnostic approach, and management have changed over time. We described the diagnosis and management of patients who developed an esophageal AL after an Ivor Lewis esophagectomy at our center.

METHODS: After IRB approval, we queried our prospectively maintained database for patients who developed an esophageal AL after esophagectomy from August 2016 through July 2022. Data pertaining to demographics, comorbidities, surgical and oncological characteristics, and clinical course were extracted and analyzed.

RESULTS: During the study period, 145 patients underwent an Ivor Lewis esophagectomy; 10 (6.9%) developed an AL, diagnosed a median of 7.5 days after surgery, and detected by enteric contents in wound drains (n = 3), endoscopy (n = 3), CT (n = 2), and contrast esophagogram (n = 2). Nine patients (90%) had an increasing white blood cell count and additional signs of sepsis. One asymptomatic patient was identified by contrast esophagography. All patients received enteral nutritional support, intravenous antibiotics, and antifungals. Primary treatment of ALs included endoscopic placement of a self-expanding metal stent (SEMS; n = 6), surgery (n = 2), and SEMS with endoluminal vacuum therapy (n = 2). One patient required surgery after SEMS placement. The median length of ICU and total hospital stays were 11.5 and 22.5 days, respectively. There was no 30-day mortality.

CONCLUSION: The incidence of esophageal ALs at our center is similar to that of other high-volume centers. Most ALs can be managed without surgery; however, ALs remain a significant source of postoperative morbidity despite clinical advancements that have improved mortality.}, } @article {pmid37830099, year = {2023}, author = {Berlowitz, DJ and Mathers, S and Hutchinson, K and Hogden, A and Carey, KA and Graco, M and Whelan, BM and Charania, S and Steyn, F and Allcroft, P and Crook, A and Sheers, NL}, title = {The complexity of multidisciplinary respiratory care in amyotrophic lateral sclerosis.}, journal = {Breathe (Sheffield, England)}, volume = {19}, number = {3}, pages = {220269}, pmid = {37830099}, issn = {1810-6838}, abstract = {UNLABELLED: Motor neurone disease/amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder with no known cure, where death is usually secondary to progressive respiratory failure. Assisting people with ALS through their disease journey is complex and supported by clinics that provide comprehensive multidisciplinary care (MDC). This review aims to apply both a respiratory and a complexity lens to the key roles and areas of practice within the MDC model in ALS. Models of noninvasive ventilation care, and considerations in the provision of palliative therapy, respiratory support, and speech and language therapy are discussed. The impact on people living with ALS of both inequitable funding models and the complexity of clinical care decisions are illustrated using case vignettes. Considerations of the impact of emerging antisense and gene modifying therapies on MDC challenges are also highlighted. The review seeks to illustrate how MDC members contribute to collective decision-making in ALS, how the sum of the parts is greater than any individual care component or health professional, and that the MDC per se adds value to the person living with ALS. Through this approach we hope to support clinicians to navigate the space between what are minimum, guideline-driven, standards of care and what excellent, person-centred ALS care that fully embraces complexity could be.

EDUCATIONAL AIMS: To highlight the complexities surrounding respiratory care in ALS.To alert clinicians to the risk that complexity of ALS care may modify the effectiveness of any specific, evidence-based therapy for ALS.To describe the importance of person-centred care and shared decision-making in optimising care in ALS.}, } @article {pmid37828541, year = {2023}, author = {Richardson, PJ and Smith, DP and de Giorgio, A and Snetkov, X and Almond-Thynne, J and Cronin, S and Mead, RJ and McDermott, CJ and Shaw, PJ}, title = {Janus kinase inhibitors are potential therapeutics for amyotrophic lateral sclerosis.}, journal = {Translational neurodegeneration}, volume = {12}, number = {1}, pages = {47}, pmid = {37828541}, issn = {2047-9158}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy/genetics/metabolism ; *Janus Kinase Inhibitors/therapeutic use ; *Neurodegenerative Diseases ; Central Nervous System/metabolism ; Janus Kinases/metabolism/therapeutic use ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a poorly treated multifactorial neurodegenerative disease associated with multiple cell types and subcellular organelles. As with other multifactorial diseases, it is likely that drugs will need to target multiple disease processes and cell types to be effective. We review here the role of Janus kinase (JAK)/Signal transducer and activator of transcription (STAT) signalling in ALS, confirm the association of this signalling with fundamental ALS disease processes using the BenevolentAI Knowledge Graph, and demonstrate that inhibitors of this pathway could reduce the ALS pathophysiology in neurons, glia, muscle fibres, and blood cells. Specifically, we suggest that inhibition of the JAK enzymes by approved inhibitors known as Jakinibs could reduce STAT3 activation and modify the progress of this disease. Analysis of the Jakinibs highlights baricitinib as a suitable candidate due to its ability to penetrate the central nervous system and exert beneficial effects on the immune system. Therefore, we recommend that this drug be tested in appropriately designed clinical trials for ALS.}, } @article {pmid37828358, year = {2023}, author = {Abrahams, S}, title = {Neuropsychological impairment in amyotrophic lateral sclerosis-frontotemporal spectrum disorder.}, journal = {Nature reviews. Neurology}, volume = {19}, number = {11}, pages = {655-667}, pmid = {37828358}, issn = {1759-4766}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/complications/diagnosis ; *Frontotemporal Dementia/complications ; *Neurodegenerative Diseases ; *Cognitive Dysfunction ; *Cognition Disorders/diagnosis/etiology ; Neuropsychological Tests ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with a rapid course, characterized by motor neuron dysfunction, leading to progressive disability and death. This Review, which is aimed at neurologists, psychologists and other health professionals who follow evidence-based practice relating to ALS and frontotemporal dementia (FTD), examines the neuropsychological evidence that has driven the reconceptualization of ALS as a spectrum disorder ranging from a pure motor phenotype to ALS-FTD. It focuses on changes in cognition and behaviour, which vary in severity across the spectrum: around 50% individuals with ALS are within the normal range, 15% meet the criteria for ALS-FTD, and the remaining 35% are in the mid-spectrum range with milder and more focal impairments. The cognitive impairments include deficits in verbal fluency, executive functions, social cognition and language, and apathy is the most prevalent behavioural change. The pattern and severity of cognitive and behavioural change predicts underlying regional cerebral dysfunction from brain imaging and post-mortem pathology. Our increased recognition of cognition and behaviour as part of the ALS phenotype has led to the development and standardization of assessment tools, which have been incorporated into research and clinical care. Measuring change over the course of the disease is vital for clinical trials, and neuropsychology is proving to be a biomarker for the earliest preclinical changes.}, } @article {pmid37827960, year = {2023}, author = {Todd, TW and Shao, W and Zhang, YJ and Petrucelli, L}, title = {The endolysosomal pathway and ALS/FTD.}, journal = {Trends in neurosciences}, volume = {46}, number = {12}, pages = {1025-1041}, pmid = {37827960}, issn = {1878-108X}, support = {R35 NS097273/NS/NINDS NIH HHS/United States ; RF1 AG062171/AG/NIA NIH HHS/United States ; RF1 AG062077/AG/NIA NIH HHS/United States ; R21 NS127331/NS/NINDS NIH HHS/United States ; P01 NS084974/NS/NINDS NIH HHS/United States ; U54 NS123743/NS/NINDS NIH HHS/United States ; R01 NS117461/NS/NINDS NIH HHS/United States ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/metabolism ; *Frontotemporal Dementia/genetics ; Mutation ; Autophagy ; C9orf72 Protein/genetics ; }, abstract = {Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are considered to be part of a disease spectrum that is associated with causative mutations and risk variants in a wide range of genes. Mounting evidence indicates that several of these genes are linked to the endolysosomal system, highlighting the importance of this pathway in ALS/FTD. Although many studies have focused on how disruption of this pathway impacts on autophagy, recent findings reveal that this may not be the whole picture: specifically, disrupting autophagy may not be sufficient to induce disease, whereas disrupting the endolysosomal system could represent a crucial pathogenic driver. In this review we discuss the connections between ALS/FTD and the endolysosomal system, including a breakdown of how disease-associated genes are implicated in this pathway. We also explore the potential downstream consequences of disrupting endolysosomal activity in the brain, outside of an effect on autophagy.}, } @article {pmid37827930, year = {2023}, author = {Cassereau, J and Bernard, E and Genestet, S and Chebbah, M and Le Clanche, S and Verschueren, A and Couratier, P}, title = {Management of amyotrophic lateral sclerosis in clinical practice: Results of the expert consensus using the Delphi methodology.}, journal = {Revue neurologique}, volume = {179}, number = {10}, pages = {1134-1144}, doi = {10.1016/j.neurol.2023.07.011}, pmid = {37827930}, issn = {0035-3787}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/therapy ; Riluzole/therapeutic use ; Motor Neurons ; Diagnosis, Differential ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a rare disease characterized by a progressive and irreversible degeneration of upper and lower motor neurons leading to death. In France, limited data exist describing the criteria used in clinical practice for diagnosis and follow-up, and how novel therapies may fit in. The objective of this Delphi panel was to obtain an overview of current French practices in ALS diagnosis, management, and follow-up by determining the scales and criteria used in clinical practice outside of clinical trials, as well as the place of a future treatment like AMX0035, acting on endoplasmic reticulum (ER) stress and mitochondrial dysfunction, in the current therapeutic strategies. A questionnaire was administered to 24 ALS healthcare providers practicing in ALS centers in France. Two rounds of remote voting were organized, before proposition of final consensus statements. Consensus was considered reached when at least 66% of the voters agreed. Consensus were obtained to define the new Gold Coast criteria as the ones used in clinical practice to establish the diagnosis of ALS, thus replacing the revised El Escorial criteria, considered too complex and now mainly used to characterize the patient populations to be included in clinical trials. The clinical factors considered to establish ALS diagnosis are mainly the demonstration of progression of the motor deficit and elimination of differential diagnoses. The ALSFRS-R scale is used in daily clinical practice to assess patient's functional impairment in terms of number of points lost, with the bulbar, respiratory, and fine motor subscores being the most important to evaluate independently. A critical medical need was identified regarding the provision of new therapeutic alternatives in ALS. The panel members would support the earliest management of patients. In this landscape, based on data from a very encouraging phase II (Centaur trial), AMX0035 represents a new tool of choice in current treatment strategies for all patients for whom experts are confident in the diagnosis of ALS, in combination with riluzole. These results will need to be confirmed by the ongoing phase III trial (Phoenix trial).}, } @article {pmid37827904, year = {2023}, author = {Santiago, JA and Karthikeyan, M and Lackey, M and Villavicencio, D and Potashkin, JA}, title = {Diabetes: a tipping point in neurodegenerative diseases.}, journal = {Trends in molecular medicine}, volume = {29}, number = {12}, pages = {1029-1044}, pmid = {37827904}, issn = {1471-499X}, support = {R01 AG062176/AG/NIA NIH HHS/United States ; }, mesh = {Humans ; *Neurodegenerative Diseases/metabolism ; Mitochondria/metabolism ; *Amyotrophic Lateral Sclerosis/genetics/metabolism ; Brain/metabolism ; *Diabetes Mellitus/metabolism ; }, abstract = {Diabetes is associated with an increased risk and progression of Alzheimer's (AD) and Parkinson's (PD) diseases. Conversely, diabetes may confer neuroprotection against amyotrophic lateral sclerosis (ALS). It has been posited that perturbations in glucose and insulin regulation, cholesterol metabolism, and mitochondrial bioenergetics defects may underlie the molecular underpinnings of diabetes effects on the brain. Nevertheless, the precise molecular mechanisms remain elusive. Here, we discuss the evidence from molecular, epidemiological, and clinical studies investigating the impact of diabetes on neurodegeneration and highlight shared dysregulated pathways between these complex comorbidities. We also discuss promising antidiabetic drugs, molecular diagnostics currently in clinical trials, and outstanding questions and challenges for future pursuit.}, } @article {pmid37827876, year = {2023}, author = {Shimizu, T and Nakayama, Y and Hayashi, K and Mochizuki, Y and Matsuda, C and Haraguchi, M and Bokuda, K and Komori, T and Takahashi, K}, title = {Somatosensory pathway dysfunction in patients with amyotrophic lateral sclerosis in a completely locked-in state.}, journal = {Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology}, volume = {156}, number = {}, pages = {253-261}, doi = {10.1016/j.clinph.2023.09.004}, pmid = {37827876}, issn = {1872-8952}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics ; Superoxide Dismutase-1 ; Evoked Potentials, Somatosensory/physiology ; Median Nerve ; }, abstract = {OBJECTIVE: To investigate somatosensory pathway function in patients with amyotrophic lateral sclerosis (ALS) dependent on invasive ventilation and in a completely locked-in state (CLIS).

METHODS: We examined median nerve somatosensory evoked potentials (SEPs) in 17 ALS patients in a CLIS, including 11 patients with sporadic ALS, one with familial ALS with genes not examined, four with a Cu/Zn superoxide-dismutase-1 (SOD1) gene variant (Val118Leu, Gly93Ser, Cys146Arg), and one with a fused-in-sarcoma gene variant (P525L). We evaluated N9, N13, N20 and P25, and central conduction time (CCT); the data were compared with those of 73 healthy controls.

RESULTS: N20 and N13 were abolished in 12 and 10 patients, and their latencies was prolonged in four and three patients, respectively. The CCT was prolonged in five patients with measurable N13 and N20. Two patients with SOD1 gene mutations had absent or slightly visible N9. Compared to the CCT and latencies and amplitudes of N13 and N20 in the controls, those in the patient cohort were significantly abnormal.

CONCLUSIONS: The central somatosensory pathway is severely involved in patients with ALS in a CLIS.

SIGNIFICANCE: Our findings suggest that median nerve SEP cannot be utilized for communication in patients with ALS in a CLIS.}, } @article {pmid37827570, year = {2024}, author = {McHutchison, CA and Wuu, J and McMillan, CT and Rademakers, R and Statland, J and Wu, G and Rampersaud, E and Myers, J and Hernandez, JP and Abrahams, S and Benatar, M and , }, title = {Temporal course of cognitive and behavioural changes in motor neuron diseases.}, journal = {Journal of neurology, neurosurgery, and psychiatry}, volume = {95}, number = {4}, pages = {316-324}, pmid = {37827570}, issn = {1468-330X}, support = {U54 NS092091/NS/NINDS NIH HHS/United States ; }, mesh = {Humans ; Male ; Middle Aged ; Female ; *Amyotrophic Lateral Sclerosis/diagnosis ; C9orf72 Protein/genetics ; *Motor Neuron Disease/genetics/complications ; *Cognitive Dysfunction/genetics/complications ; Cognition/physiology ; Neuropsychological Tests ; }, abstract = {BACKGROUND: Cognitive and behavioural dysfunction may occur in people with motor neuron disease (MND), with some studies suggesting an association with the C9ORF72 repeat expansion. Their onset and progression, however, is poorly understood. We explored how cognition and behaviour change over time, and whether demographic, clinical and genetic factors impact these changes.

METHODS: Participants with MND were recruited through the Phenotype-Genotype-Biomarker study. Every 3-6 months, the Edinburgh Cognitive and Behavioural ALS Screen (ECAS) was used to assess amyotrophic lateral sclerosis (ALS) specific (executive functioning, verbal fluency, language) and ALS non-specific (memory, visuospatial) functions. Informants reported on behaviour symptoms via semi-structured interview.

RESULTS: Participants with neuropsychological data at ≥3 visits were included (n=237, mean age=59, 60% male), of which 18 (8%) were C9ORF72 positive. Baseline cognitive impairment was apparent in 18 (8%), typically in ALS specific domains, and associated with lower education, but not C9ORF72 status. Cognition, on average, remained stable over time, with two exceptions: (1) C9ORF72 carriers declined in all ECAS domains, (2) 8%-9% of participants with baseline cognitive impairment further declined, primarily in the ALS non-specific domain, which was associated with less education. Behavioural symptoms were uncommon.

CONCLUSIONS: In this study, cognitive dysfunction was less common than previously reported and remained stable over time for most. However, cognition declines longitudinally in a small subset, which is not entirely related to C9ORF72 status. Our findings raise questions about the timing of cognitive impairment in MND, and whether it arises during early clinically manifest disease or even prior to motor manifestations.}, } @article {pmid37827425, year = {2024}, author = {Jia, H and Li, Z and Guo, F and Hua, Z and Zhou, X and Li, X and Li, R and Liu, Q and Liu, Y and Dong, H}, title = {Cortical structure and the risk of amyotrophic lateral sclerosis: A bidirectional Mendelian randomization study.}, journal = {Progress in neuro-psychopharmacology & biological psychiatry}, volume = {129}, number = {}, pages = {110872}, doi = {10.1016/j.pnpbp.2023.110872}, pmid = {37827425}, issn = {1878-4216}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnostic imaging/genetics ; Genome-Wide Association Study ; Mendelian Randomization Analysis ; Reproducibility of Results ; Magnetic Resonance Imaging/methods ; }, abstract = {BACKGROUND: Current observational studies indicate progressive brain atrophy is closely associated with the clinical feature of amyotrophic lateral sclerosis. However, it is unclear whether the changes in cortical structure are the cause or result of ALS. Our study aimed to investigate the causal relationship between cortical structure and ALS risk using a bidirectional two-sample MR study.

METHODS: We collected publicly available genome-wide association studies' summary statistics for cortical structure from UK Biobank and ENIGMA consortium (n = 33,992) and ALS from the Project MinE (n = 138,086). We used the inverse variance weighted method (IVW) as primary analysis in order to evaluate the causal effects. In addition, the weighted median and MR Egger methods were performed to ensure the robustness and reliability of the IVW results.

RESULTS: We found the decreased surface of the paracentral lobule and thickness of the frontal pole and middle temporal lobe were suggestively associated with an increased risk of ALS as well as the increased surface of medial orbitofrontal and middle temporal lobe. In another aspect, the causalities between the susceptibility to ALS and the volume of the transverse temporal gyrus and superior temporal gyrus were negative. Besides, the susceptibility to ALS might also contribute to an increased thickness of the postcentral gyrus and superior parietal gyrus.

CONCLUSION: In this two-sample MR analysis, we observed that multiple cortical brain regions are associated with a higher ALS risk. Further research into the underlying mechanisms is required to back up our findings.}, } @article {pmid37827137, year = {2024}, author = {Heckmann, JG and Kiem, M and Immich, G}, title = {Forest Therapy as a Nature-Based Intervention: An Option for Neurological Rehabilitation?.}, journal = {Complementary medicine research}, volume = {31}, number = {1}, pages = {56-63}, doi = {10.1159/000534533}, pmid = {37827137}, issn = {2504-2106}, mesh = {Humans ; *Medicine ; *Neurological Rehabilitation ; *Sleep Wake Disorders ; *Stroke/therapy ; *Dementia ; Observational Studies as Topic ; }, abstract = {BACKGROUND: Forest therapy demonstrates positive effects on mood, immune system, stress levels, and general well-being. Studies on depression, stress-related illnesses, sleep disorders, and arterial hypertension have provided evidence-based proof of this.

SUMMARY: The aim of this review was to examine the possible effects of forest therapy with regard to its evidence in the treatment of chronic neurological diseases such as stroke in the rehabilitation phase, Parkinson's disease, dementia, and multiple sclerosis. Therefore, the electronic databases Medline, Scopus, and Cochrane were searched for such clinical trials for the years 1970 to mid-2023 without language restriction. The literature search revealed only few studies with positive indications but too few cases to be able to make generalizable evidence-based statements. In terms of improvement in the Hamilton Depression Scale analysis of two studies in stroke patients showed slight benefits in the forest therapy group (standard mean difference -0.43; 95% CI: -0.76 to -0.10; p < 0.01). One observational study revealed a higher rate of stroke survival in patients living in marked greenness. Few nature-based interventions in dementia patients showed certain benefits in particular details.

KEY MESSAGES: There are no evidence-based results on the benefit of forest therapy for chronic neurological diseases. However, there are hints that forest therapy could have a positive benefit. Therefore, a proposal for forest therapy as a component of multimodal neurological rehabilitation is presented.

UNLABELLED: HintergrundDie Waldtherapie zeigt positive Auswirkungen auf die Stimmung, das Immunsystem, das Stressniveau und das allgemeine Wohlbefinden. Studien zu Depressionen, stressbedingten Erkrankungen, Schlafstörungen und arteriellem Bluthochdruck haben dies evidenzbasiert belegt.ZusammenfassungZiel dieser Übersichtsarbeit war es, die möglichen Wirkungen der Waldtherapie im Hinblick auf ihre Evidenz bei der Behandlung chronischer neurologischer Erkrankungen wie Schlaganfall in der Rehabilitationsphase, Morbus Parkinson, Demenz und Multiple Sklerose zu untersuchen. Dazu wurden die elektronischen Datenbanken Medline, Scopus und Cochrane für die Jahre 1970 bis Mitte 2023 ohne sprachliche Einschränkung nach solchen klinischen Studien durchsucht. Die Literaturrecherche ergab nur wenige Studien mit positiven Indikationen, aber zu wenigen Fällen, um verallgemeinerbare evidenzbasierte Aussagen machen zu können. Im Hinblick auf Verbesserung in der Hamilton Depressionsskala zeigte die Analyse von 2 Studien bei Schlaganfallpatienten leichte Vorteile der Waldtherapiegruppen (Standard Mean Difference −0.43; 95% CI: -0.76- -0,10; p < 0.01). Eine Beobachtungsstudie ergab eine höhere Schlaganfall-Überlebensrate bei Patienten, die in ausgeprägtem Grün leben. Einige naturbasierte Interventionen bei Demenzpatienten zeigten in einzelnen Parametern gewisse Vorteile.FazitEs gibt bis dato keine verallgemeinerbaren evidenzbasierten Ergebnisse zum Nutzen der Waldtherapie bei chronischen neurologischen Erkrankungen. Es gibt jedoch Hinweise, dass die Waldtherapie einen positiven Nutzen haben könnte. Es wird daher ein Vorschlag für eine Waldtherapie als Bestandteil einer multimodalen neurologischen Rehabilitation vorgestellt.}, } @article {pmid37823684, year = {2024}, author = {Marlin, E and Valencia, M and Peregrín, N and Ferrero, R and Nicolás, MJ and Vinueza-Gavilanes, R and Pineda-Lucena, A and Artieda, J and Arrasate, M and Aragón, T}, title = {Pharmacological inhibition of the integrated stress response accelerates disease progression in an amyotrophic lateral sclerosis mouse model.}, journal = {British journal of pharmacology}, volume = {181}, number = {3}, pages = {495-508}, doi = {10.1111/bph.16260}, pmid = {37823684}, issn = {1476-5381}, support = {Predoctoral Fellowship//AC-CIMA/ ; Proyectos I+D 2017//Fundación para la Investigación Médica Aplicada/ ; 0011-0537-2018-000006 Predoctoral fellowship//Gobierno de Navarra, Departamento de Universidad, Innovación y Transformación Digital/ ; Intramural IdiSNA 2022//Instituto de Investigación Sanitaria de Navarra (IdiSNA)/ ; BFU2017-90043-P MICINN/ AEI/10.13039/501100011033//Ministerio de Ciencia e Innovación/ ; PID2020-120497RB-I00 MICINN/ AEI /10.13039/501100011//Ministerio de Ciencia e Innovación/ ; //Proyecto Intramural IdisNa 2022/ ; //Fundación para la Investigación Médica Aplicada (FIMA)/ ; 0011-0537-2018-000006//Departamento de Educación, Gobierno de Navarra/ ; //Asociación de Amigos (ADA)/ ; }, mesh = {Humans ; Mice ; Animals ; *Amyotrophic Lateral Sclerosis/drug therapy/metabolism ; Superoxide Dismutase-1/genetics ; Eukaryotic Initiation Factor-2B ; Superoxide Dismutase/metabolism ; Mice, Transgenic ; Disease Progression ; Disease Models, Animal ; }, abstract = {BACKGROUND AND PURPOSE: The integrated stress response (ISR) regulates translation in response to diverse stresses. ISR activation has been documented in amyotrophic lateral sclerosis (ALS) patients and ALS experimental models. In experimental models, both ISR stimulation and inhibition prevented ALS neurodegeneration; however, which mode of ISR regulation would work in patients is still debated. We previously demonstrated that the ISR modulator ISRIB (Integrated Stress Response InhiBitor, an eIF2B activator) enhances survival of neurons expressing the ALS neurotoxic allele SOD1 G93A. Here, we tested the effect of two ISRIB-like eIF2B activators (2BAct and PRXS571) in the disease progression of transgenic SOD1[G93A] mice.

EXPERIMENTAL APPROACH: After biochemical characterization in primary neurons, SOD1[G93A] mice were treated with 2BAct and PRXS571. Muscle denervation of vulnerable motor units was monitored with a longitudinal electromyographic test. We used a clinical score to document disease onset and progression; force loss was determined with the hanging wire motor test. Motor neuronal survival was assessed by immunohistochemistry.

KEY RESULTS: In primary neurons, 2BAct and PRXS571 relieve the ISR-imposed translational inhibition while maintaining high ATF4 levels. Electromyographic recordings evidenced an earlier and more dramatic muscle denervation in treated SOD1[G93A] mice that correlated with a decrease in motor neuron survival. Both compounds anticipated disease onset and shortened survival time.

CONCLUSION AND IMPLICATIONS: 2BAct and PRXS571 anticipate disease onset, aggravating muscle denervation and motor neuronal death of SOD1[G93A] mice. This study reveals that the ISR works as a neuroprotective pathway in ALS motor neurons and reveals the toxicity that eIF2B activators may display in ALS patients.}, } @article {pmid37823580, year = {2023}, author = {Mehta, AK and Sarmet, M and Maiser, S and Meyer, JA and Kolodziejczak, S and Washington, K and Simmons, Z}, title = {Quality-of-life assessment instruments used across ALS clinics.}, journal = {Muscle & nerve}, volume = {68}, number = {6}, pages = {865-872}, doi = {10.1002/mus.27985}, pmid = {37823580}, issn = {1097-4598}, mesh = {Humans ; *Quality of Life ; *Amyotrophic Lateral Sclerosis/diagnosis/therapy ; Palliative Care ; Surveys and Questionnaires ; Ambulatory Care ; }, abstract = {INTRODUCTION/AIMS: Instruments have been developed to assess quality of life (QoL) among people with amyotrophic lateral sclerosis (ALS). It is unclear whether these are utilized regularly in the clinical setting to guide individual patient care. In this study we aimed to understand the current use of instruments and existing barriers to assessing QoL in clinical ALS care.

METHODS: An anonymous survey developed by Northeast ALS (NEALS) Consortium Palliative Committee members was distributed to all multidisciplinary NEALS members. Data were summarized via calculation of descriptive statistics. ALS Center characteristics were compared using chi-square and Fisher exact tests for categorical variables.

RESULTS: Seventy-three (6.4%) of the 1132 NEALS members responded to the survey, representing 148 clinics, 49.3% of whom reported assessing QoL during clinic visits. The most used ALS-specific instruments were the ALS Assessment Questionnaire (19.4%) and Amyotrophic Lateral Sclerosis Specific Quality of Life scale (16.6%). Barriers reported were uncertainty regarding which instrument to use and length of visits. QoL assessment was not significantly correlated with length of clinic visit but with access to specialty palliative care.

DISCUSSION: QoL assessments are performed by some, but not all, ALS centers during clinical visits. Although this study did have a low number of responding centers, the percentage, the proportion is similar to that seen in earlier studies, which limits the findings' generalizability. The value of QoL assessments' impact on outcomes should be further investigated and, if warranted, creative ways sought to increase the frequency of their use, including patient self-assessments before clinic and/or the use of teleheath to reduce the length of clinic visits.}, } @article {pmid37822527, year = {2023}, author = {Colombo, E and Gentile, F and Maranzano, A and Doretti, A and Verde, F and Olivero, M and Gagliardi, D and Faré, M and Meneri, M and Poletti, B and Maderna, L and Corti, S and Corbo, M and Morelli, C and Silani, V and Ticozzi, N}, title = {The impact of upper motor neuron involvement on clinical features, disease progression and prognosis in amyotrophic lateral sclerosis.}, journal = {Frontiers in neurology}, volume = {14}, number = {}, pages = {1249429}, pmid = {37822527}, issn = {1664-2295}, } @article {pmid37821950, year = {2023}, author = {Košir, M and Možina, H and Podbregar, M}, title = {Skeletal muscle oxygenation during cardiopulmonary resuscitation as a predictor of return of spontaneous circulation: a pilot study.}, journal = {European journal of medical research}, volume = {28}, number = {1}, pages = {418}, pmid = {37821950}, issn = {2047-783X}, mesh = {Adult ; Humans ; Male ; Aged ; Female ; *Cardiopulmonary Resuscitation/methods ; Pilot Projects ; Return of Spontaneous Circulation ; Cerebrovascular Circulation/physiology ; *Out-of-Hospital Cardiac Arrest/therapy ; }, abstract = {BACKGROUND: Near-infrared spectroscopy (NIRS) provides regional tissue oxygenation (rSO2) even in pulseless states, such as out-of-hospital cardiac arrest (OHCA). Brain rSO2 seems to be important predictor of return of spontaneous circulation (ROSC) during cardiopulmonary resuscitation (CPR). Aim of our study was to explore feasibility for monitoring and detecting changes of skeletal muscle rSO2 during resuscitation.

METHODS: Skeletal muscle and brain rSO2 were measured by NIRS (SenSmart Model X-100, Nonin, USA) during CPR in adult patient with OHCA. Start (basal) rSO2, maximal during CPR (maximal) and difference between maximal-minimal rSO2 (delta-rSO2), were recorded. Patients were divided into ROSC and NO-ROSC group.

RESULTS: 20 patients [age: 66.0ys (60.5-79.5), 65% male] with OHCA [50% witnessed, 70% BLS, time to ALS 13.5 min (11.0-19.0)] were finally analyzed. ROSC was confirmed in 5 (25%) patients. Basal and maximal skeletal muscle rSO2 were higher in ROSC compared to NO-ROSC group [49.0% (39.7-53.7) vs. 15.0% (12.0-25.2), P =  0.006; 76.0% (52.7-80.5) vs. 34.0% (18.0-49.5), P =  0.005, respectively]. There was non-linear cubic relationship between time of collapse and basal skeletal muscle rSO2 in witnessed OHCA and without BLS (F-ratio = 9.7713, P =  0.0261). There was correlation between maximal skeletal muscle and brain rSO2 (n = 18, rho: 0.578, P =   0.0121).

CONCLUSIONS: Recording of skeletal muscle rSO2 during CPR in patients with OHCA is feasible. Basal and maximal skeletal muscle rSO2 were higher in ROSC compared to NO-ROSC group. Clinical trial registration number ClinicalTrials.gov, NCT04058925, registered on: 16th August 2019. URL of trial registry record: https://www.

CLINICALTRIALS: gov/ct2/show/NCT04058925?titles=Tissue+Oxygenation+During+Cardiopulmonary+Resuscitation+as+a+Predictor+of+Return+of+Spontaneous+Circulation&draw=2&rank=1 .}, } @article {pmid37821429, year = {2023}, author = {Zhang, S and Tong, M and Zheng, D and Huang, H and Li, L and Ungermann, C and Pan, Y and Luo, H and Lei, M and Tang, Z and Fu, W and Chen, S and Liu, X and Zhong, Q}, title = {C9orf72-catalyzed GTP loading of Rab39A enables HOPS-mediated membrane tethering and fusion in mammalian autophagy.}, journal = {Nature communications}, volume = {14}, number = {1}, pages = {6360}, pmid = {37821429}, issn = {2041-1723}, mesh = {Animals ; Autophagy ; C9orf72 Protein/genetics/metabolism ; Catalysis ; Guanosine Triphosphate/metabolism ; Mammals/metabolism ; *Membrane Fusion/physiology ; Vacuoles/metabolism ; }, abstract = {The multi-subunit homotypic fusion and vacuole protein sorting (HOPS) membrane-tethering complex is required for autophagosome-lysosome fusion in mammals, yet reconstituting the mammalian HOPS complex remains a challenge. Here we propose a "hook-up" model for mammalian HOPS complex assembly, which requires two HOPS sub-complexes docking on membranes via membrane-associated Rabs. We identify Rab39A as a key small GTPase that recruits HOPS onto autophagic vesicles. Proper pairing with Rab2 and Rab39A enables HOPS complex assembly between proteoliposomes for its tethering function, facilitating efficient membrane fusion. GTP loading of Rab39A is important for the recruitment of HOPS to autophagic membranes. Activation of Rab39A is catalyzed by C9orf72, a guanine exchange factor associated with amyotrophic lateral sclerosis and familial frontotemporal dementia. Constitutive activation of Rab39A can rescue autophagy defects caused by C9orf72 depletion. These results therefore reveal a crucial role for the C9orf72-Rab39A-HOPS axis in autophagosome-lysosome fusion.}, } @article {pmid37819987, year = {2023}, author = {Zhang, Z and Sun, S}, title = {Linking ALS mutations to the disruption of the MHC-II pathway.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {120}, number = {43}, pages = {e2315240120}, pmid = {37819987}, issn = {1091-6490}, support = {R01 AG078948/AG/NIA NIH HHS/United States ; RF1 NS113820/NS/NINDS NIH HHS/United States ; RF1 NS127925/NS/NINDS NIH HHS/United States ; }, mesh = {*Antigen Presentation ; *Histocompatibility Antigens Class II/immunology ; Genes, MHC Class II ; Mutation ; }, } @article {pmid37819399, year = {2023}, author = {Feng, CY and Han, JR and Lu, CY and Gu, L and Li, S and Lian, WH and Dong, L and Li, WJ}, title = {Telluribacter roseus sp. nov., Isolated from the Kumtag Desert Soil.}, journal = {Current microbiology}, volume = {80}, number = {12}, pages = {365}, pmid = {37819399}, issn = {1432-0991}, support = {32061143043//National Natural Science Foundation of China/ ; 32270076//National Natural Science Foundation of China/ ; 32000005//National Natural Science Foundation of China/ ; 2022xjkk1204//the Third Xinjiang Scientific Expedition Program/ ; 2023A1515012020//Guangdong Basic and Applied Basic Research Foundation, China/ ; MB2020KF05//Guangdong Provincial Key Laboratory of Chinese Medicine for Prevention and Treatment of Refractory Chronic Diseases/ ; }, mesh = {*Soil ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; Bacterial Typing Techniques ; DNA, Bacterial/genetics ; *Phospholipids/chemistry ; Fatty Acids/chemistry ; Sequence Analysis, DNA ; }, abstract = {A pink-pigmented bacterium, designated as strain SYSU D00476[T], was isolated from sandy soil collected from the Kumtag Desert in China. Colonies were opaque, smooth and of a slight convexity with a clearly defined border. Cells were rod-shaped, Gram-stain-negative, catalase- and oxidase-positive. Growth occurred at 4-45 ℃ (optimum at 28-30 ℃), pH 6.0-8.0 (optimum at 7.0), and with 0-3.0% NaCl (w/v, optimum at 0-2.0%). Major fatty acids (> 10%) were C16:0, summed feature 3 (C16:1 ω7c and/or C16:1 ω6c), iso-C17:0 3-OH and iso-C15:0. Polar lipids comprised of three unidentified polar aminolipids (ALs), two unidentified aminophosphoglycolipids (APLs), one unidentified glycolipid (GL) and three unidentified phospholipids (PLs). The predominant respiratory quinone was MK-7. The genomic DNA G + C content was 50.5%. The low digital DNA-DNA hybridization (dDDH, 27.4%) and average nucleotide identity (ANI, 85%) values between strain SYSU D00476[T] and Telluribacter humicola KCTC 42819[T] indicated that SYSU D00476[T] represent a distinct species. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain SYSU D00476[T] belonged to the genus Telluribacter, showing 97.5% similarity with T. humicola KCTC 42819[T]. All these data support that strain SYSU D00476[T] represent a novel species of the genus Telluribacter within the family Spirosomataceae, named as Telluribacter roseus sp. nov. The type strain is SYSU D00476[T] (= KCTC 82285[T] = CGMCC 1.18647[T] = MCCC 1K04983[T]).}, } @article {pmid37819053, year = {2023}, author = {Necarsulmer, JC and Simon, JM and Evangelista, BA and Chen, Y and Tian, X and Nafees, S and Marquez, AB and Jiang, H and Wang, P and Ajit, D and Nikolova, VD and Harper, KM and Ezzell, JA and Lin, FC and Beltran, AS and Moy, SS and Cohen, TJ}, title = {RNA-binding deficient TDP-43 drives cognitive decline in a mouse model of TDP-43 proteinopathy.}, journal = {eLife}, volume = {12}, number = {}, pages = {}, pmid = {37819053}, issn = {2050-084X}, support = {F31 NS122242/NS/NINDS NIH HHS/United States ; R01 NS105981/NS/NINDS NIH HHS/United States ; P50 HD103573/HD/NICHD NIH HHS/United States ; P30NS045892/NS/NINDS NIH HHS/United States ; P30 NS045892/NS/NINDS NIH HHS/United States ; T32 GM133364/GM/NIGMS NIH HHS/United States ; F30 AG072786/AG/NIA NIH HHS/United States ; R01NS105981/NS/NINDS NIH HHS/United States ; UM1TR004406/TR/NCATS NIH HHS/United States ; T32 GM008719/GM/NIGMS NIH HHS/United States ; UM1 TR004406/TR/NCATS NIH HHS/United States ; F31NS122242/NS/NINDS NIH HHS/United States ; U54 HD079124/HD/NICHD NIH HHS/United States ; F30AG072786/AG/NIA NIH HHS/United States ; 1T32GM133364-01A1/GM/NIGMS NIH HHS/United States ; 5T32GM008719-19/GM/NIGMS NIH HHS/United States ; }, mesh = {Humans ; Animals ; Mice ; *TDP-43 Proteinopathies/genetics/metabolism ; DNA-Binding Proteins/genetics/metabolism ; *Frontotemporal Lobar Degeneration/genetics/metabolism ; *Amyotrophic Lateral Sclerosis/genetics ; *Frontotemporal Dementia/genetics ; Disease Models, Animal ; *Cognitive Dysfunction ; RNA ; }, abstract = {TDP-43 proteinopathies including frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS) are neurodegenerative disorders characterized by aggregation and mislocalization of the nucleic acid-binding protein TDP-43 and subsequent neuronal dysfunction. Here, we developed endogenous models of sporadic TDP-43 proteinopathy based on the principle that disease-associated TDP-43 acetylation at lysine 145 (K145) alters TDP-43 conformation, impairs RNA-binding capacity, and induces downstream mis-regulation of target genes. Expression of acetylation-mimic TDP-43[K145Q] resulted in stress-induced nuclear TDP-43 foci and loss of TDP-43 function in primary mouse and human-induced pluripotent stem cell (hiPSC)-derived cortical neurons. Mice harboring the TDP-43[K145Q] mutation recapitulated key hallmarks of FTLD, including progressive TDP-43 phosphorylation and insolubility, TDP-43 mis-localization, transcriptomic and splicing alterations, and cognitive dysfunction. Our study supports a model in which TDP-43 acetylation drives neuronal dysfunction and cognitive decline through aberrant splicing and transcription of critical genes that regulate synaptic plasticity and stress response signaling. The neurodegenerative cascade initiated by TDP-43 acetylation recapitulates many aspects of human FTLD and provides a new paradigm to further interrogate TDP-43 proteinopathies.}, } @article {pmid37818935, year = {2024}, author = {Rehmann, R}, title = {Editorial for: "Quantitative MRI Analysis of Brachial Plexus and Limb-Girdle Muscles in Upper Extremity Onset Amyotrophic Lateral Sclerosis".}, journal = {Journal of magnetic resonance imaging : JMRI}, volume = {60}, number = {1}, pages = {302-303}, doi = {10.1002/jmri.29051}, pmid = {37818935}, issn = {1522-2586}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnostic imaging ; *Magnetic Resonance Imaging/methods ; *Brachial Plexus/diagnostic imaging ; *Muscle, Skeletal/diagnostic imaging ; Upper Extremity/diagnostic imaging ; }, } @article {pmid37818590, year = {2023}, author = {Grima, N and Liu, S and Southwood, D and Henden, L and Smith, A and Lee, A and Rowe, DB and D'Silva, S and Blair, IP and Williams, KL}, title = {RNA sequencing of peripheral blood in amyotrophic lateral sclerosis reveals distinct molecular subtypes: Considerations for biomarker discovery.}, journal = {Neuropathology and applied neurobiology}, volume = {49}, number = {6}, pages = {e12943}, pmid = {37818590}, issn = {1365-2990}, support = {//Motor Neurone Disease Research Australia/ ; //National Health and Medical Research Council/ ; 2011120//NHMRC/ ; //FightMND/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/genetics ; *Neurodegenerative Diseases ; Australia ; Biomarkers ; Sequence Analysis, RNA ; }, abstract = {AIM: Amyotrophic lateral sclerosis (ALS) is a heterogeneous neurodegenerative disease with limited therapeutic options. A key factor limiting the development of effective therapeutics is the lack of disease biomarkers. We sought to assess whether biomarkers for diagnosis, prognosis or cohort stratification could be identified by RNA sequencing (RNA-seq) of ALS patient peripheral blood.

METHODS: Whole blood RNA-seq data were generated for 96 Australian sporadic ALS (sALS) cases and 48 healthy controls (NCBI GEO accession GSE234297). Differences in sALS-control gene expression, transcript usage and predicted leukocyte proportions were assessed, with pathway analysis used to predict the activity state of biological processes. Weighted Gene Co-expression Network Analysis (WGCNA) and machine learning algorithms were applied to search for diagnostic and prognostic gene expression patterns. Unsupervised clustering analysis was employed to determine whether sALS patient subgroups could be detected.

RESULTS: Two hundred and forty-five differentially expressed genes were identified in sALS patients relative to controls, with enrichment of immune, metabolic and stress-related pathways. sALS patients also demonstrated switches in transcript usage across a small set of genes. We established a classification model that distinguished sALS patients from controls with an accuracy of 78% (sensitivity: 79%, specificity: 75%) using the expression of 20 genes. Clustering analysis identified four patient subgroups with gene expression signatures and immune cell proportions reflective of distinct peripheral effects.

CONCLUSIONS: Our findings suggest that peripheral blood RNA-seq can identify diagnostic biomarkers and distinguish molecular subtypes of sALS patients however, its prognostic value requires further investigation.}, } @article {pmid37817804, year = {2023}, author = {Cui, S and Zhang, T and Xiong, X and Zhao, J and Cao, Q and Zhou, H and Xia, XG}, title = {Detergent-insoluble PFN1 inoculation expedites disease onset and progression in PFN1 transgenic rats.}, journal = {Frontiers in neuroscience}, volume = {17}, number = {}, pages = {1279259}, pmid = {37817804}, issn = {1662-4548}, support = {R01 NS089701/NS/NINDS NIH HHS/United States ; R01 NS099635/NS/NINDS NIH HHS/United States ; R01 NS110455/NS/NINDS NIH HHS/United States ; RF1 AG064822/AG/NIA NIH HHS/United States ; }, abstract = {Accumulating evidence suggests a gain of elusive toxicity in pathogenically mutated PFN1. The prominence of PFN1 aggregates as a pivotal pathological hallmark in PFN1 transgenic rats underscores the crucial involvement of protein aggregation in the initiation and progression of neurodegeneration. Detergent-insoluble materials were extracted from the spinal cords of paralyzed rats afflicted with ALS and were intramuscularly administered to asymptomatic recipient rats expressing mutant PFN1, resulting in an accelerated development of PFN1 inclusions and ALS-like phenotypes. This effect diminished when the extracts derived from wildtype PFN1 transgenic rats were employed, as detergent-insoluble PFN1 was detected exclusively in mutant PFN1 transgenic rats. Consequently, the factor influencing the progression of ALS pathology in recipient rats is likely associated with the presence of detergent-insoluble PFN1 within the extracted materials. Noteworthy is the absence of disease course modification upon administering detergent-insoluble extracts to rats that already displayed PFN1 inclusions, suggesting a seeding rather than augmenting role of such extracts in initiating neuropathological changes. Remarkably, pathogenic PFN1 exhibited an enhanced affinity for the molecular chaperone DNAJB6, leading to the sequestration of DNAJB6 within protein inclusions, thereby depleting its availability for cellular functions. These findings shed light on a novel mechanism that underscores the prion-like characteristics of pathogenic PFN1 in driving neurodegeneration in the context of PFN1-related ALS.}, } @article {pmid37816542, year = {2024}, author = {McHenry, KL}, title = {Airway Clearance Strategies and Secretion Management in Amyotrophic Lateral Sclerosis.}, journal = {Respiratory care}, volume = {69}, number = {2}, pages = {227-237}, pmid = {37816542}, issn = {1943-3654}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/complications/therapy ; Respiratory Therapy/methods ; *Chest Wall Oscillation ; Bodily Secretions ; *Insufflation/methods ; Cough/etiology ; *Respiratory Insufficiency/therapy ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a rare, neurodegenerative motor neuron disease that affects voluntary muscle movement. Often, difficulty in coughing, breathing, and swallowing are sequela associated with the condition, and the presence of bulbar muscle predominant weakness results in deleterious effects on airway clearance and secretion management. This narrative review will provide practical guidance for clinicians treating this population. Cough insufficiency in this population typically manifests as a prolonged, slow, weak cough effort that impedes the clearability of secretions and airway protection. Dystussia and dysphagia frequently occur simultaneously in bulbar dysfunction, subsequently impacting respiratory health. Measures of respiratory strength should be obtained and monitored every 3-6 months, preferably in a multidisciplinary clinic setting. Cough augmentation, whether manual or mechanical techniques, should be sought as early in the disease progression as possible to adequately control secretions in the proximal airways. This airway clearance strategy can aid in the prevention and treatment of respiratory tract infections (RTIs), which can pose a significant clinical hurdle to those with ALS. The use of mechanical insufflation-exsufflation may be complicated by severe bulbar dysfunction rendering this technique ineffective. Though peripheral airway clearance strategies, such as high-frequency chest-wall compression, have the advantage of being less impacted by bulbar dysfunction, it is only recommended this modality be used in conjunction with, versus in lieu of, proximal strategies. Salivary secretion management includes the use of anticholinergics, botulinum toxin, and radiation therapy depending on severity and desire for relief.}, } @article {pmid37815936, year = {2023}, author = {Shammas, MK and Nie, Y and Gilsrud, A and Huang, X and Narendra, DP and Chinnery, PF}, title = {CHCHD10 mutations induce tissue-specific mitochondrial DNA deletions with a distinct signature.}, journal = {Human molecular genetics}, volume = {33}, number = {1}, pages = {91-101}, pmid = {37815936}, issn = {1460-2083}, support = {212219/Z/18/Z/WT_/Wellcome Trust/United Kingdom ; 224486/Z/21/Z/WT_/Wellcome Trust/United Kingdom ; MR/S005021/1/MRC_/Medical Research Council/United Kingdom ; MR/S035699/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Animals ; Humans ; Mice ; *Amyotrophic Lateral Sclerosis/genetics ; DNA, Mitochondrial/genetics/metabolism ; *Frontotemporal Dementia/genetics ; Mitochondria/metabolism ; *Mitochondrial Proteins/genetics/metabolism ; Mutation ; }, abstract = {Mutations affecting the mitochondrial intermembrane space protein CHCHD10 cause human disease, but it is not known why different amino acid substitutions cause markedly different clinical phenotypes, including amyotrophic lateral sclerosis-frontotemporal dementia, spinal muscular atrophy Jokela-type, isolated autosomal dominant mitochondrial myopathy and cardiomyopathy. CHCHD10 mutations have been associated with deletions of mitochondrial DNA (mtDNA deletions), raising the possibility that these explain the clinical variability. Here, we sequenced mtDNA obtained from hearts, skeletal muscle, livers and spinal cords of WT and Chchd10 G58R or S59L knockin mice to characterise the mtDNA deletion signatures of the two mutant lines. We found that the deletion levels were higher in G58R and S59L mice than in WT mice in some tissues depending on the Chchd10 genotype, and the deletion burden increased with age. Furthermore, we observed that the spinal cord was less prone to the development of mtDNA deletions than the other tissues examined. Finally, in addition to accelerating the rate of naturally occurring deletions, Chchd10 mutations also led to the accumulation of a novel set of deletions characterised by shorter direct repeats flanking the deletion breakpoints. Our results indicate that Chchd10 mutations in mice induce tissue-specific deletions which may also contribute to the clinical phenotype associated with these mutations in humans.}, } @article {pmid37815307, year = {2024}, author = {Liu, KF and Ramachandran, S and Chang, CW and Chen, RF and Huang, CH and Huang, HT and Lee, CC and Li, YT and Kuo, YR}, title = {The Synergistic Effect of Full-Spectrum Light Therapy and Transient Immunosuppressants Prolonged Allotransplant Survival.}, journal = {Plastic and reconstructive surgery}, volume = {154}, number = {4}, pages = {775-783}, doi = {10.1097/PRS.0000000000011135}, pmid = {37815307}, issn = {1529-4242}, support = {SH11003//Kaohsiung Medical University Hospital, Taiwan./ ; }, mesh = {Animals ; *Immunosuppressive Agents/therapeutic use ; *Graft Survival/drug effects/immunology ; *Rats, Inbred Lew ; Rats ; *Vascularized Composite Allotransplantation/methods ; *Hindlimb/transplantation ; Male ; Combined Modality Therapy ; Cyclosporine ; Graft Rejection/prevention & control/immunology ; Phototherapy/methods ; Rats, Inbred BN ; Antilymphocyte Serum ; }, abstract = {BACKGROUND: The lifelong administration of immunosuppressants remains the largest drawback in vascularized composite allotransplantation (VCA). Therefore, developing alternative strategies to minimize the long-term use of immunosuppressive agents is crucial. This study investigated whether full-spectrum bright light therapy (FBLT) combined with short-term immunosuppressant therapy could prolong VCA survival in a rodent hindlimb model.

METHODS: Hindlimb allotransplantation was conducted from Brown-Norway to Lewis rats, and the rats were divided into 4 groups. Group 1 did not receive treatment as a rejection control. Group 2 received FBLT alone. Group 3 was treated with short-term antilymphocyte serum (ALS) and cyclosporine A (CsA). Group 4 was administered short-term ALS/CsA combined with FBLT for 8 weeks. Peripheral blood and transplanted tissues were collected for analysis.

RESULTS: The results revealed median survival time of FBLT alone (group 2) did not increase allograft survival compared with the control (group 1). However, in group 4, FBLT combined with short-term ALS/CsA, median composite tissue allograft survival time (266 days) was significantly prolonged compared with groups 1 (11 days), 2 (10 days), and 3 (41 days) (P < 0.01). Group 4 also showed a significant increase in regulatory T cells (P = 0.04) and transforming growth factor-β1 levels (P = 0.02), and a trend toward a decrease in interleukin-1β levels (P = 0.03) at 16 weeks after transplantation as compared with control (group 1).

CONCLUSIONS: FBLT combined with short-term immunosuppressants prolonged allotransplant survival by modulating T-cell regulatory functions and antiinflammatory cytokine expression. This approach could be a potential strategy to increase VCA survival.

CLINICAL RELEVANCE STATEMENT: Full-spectrum light therapy could be a potential strategy to increase vascularized composite allotransplant survival.}, } @article {pmid37815224, year = {2024}, author = {Northall, A and Doehler, J and Weber, M and Tellez, I and Petri, S and Prudlo, J and Vielhaber, S and Schreiber, S and Kuehn, E}, title = {Multimodal layer modelling reveals in vivo pathology in amyotrophic lateral sclerosis.}, journal = {Brain : a journal of neurology}, volume = {147}, number = {3}, pages = {1087-1099}, pmid = {37815224}, issn = {1460-2156}, support = {2019-A03//Else Kröner Fresenius Stiftung/ ; KU 3711/2-1//Deutsche Forschungsgemeinschaft/ ; 501214112//SCHR/ ; }, mesh = {Humans ; Calcium ; *Amyotrophic Lateral Sclerosis/diagnostic imaging ; *Neurodegenerative Diseases ; *Dermatitis ; Iron ; *Demyelinating Diseases ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a rapidly progressing neurodegenerative disease characterized by the loss of motor control. Current understanding of ALS pathology is largely based on post-mortem investigations at advanced disease stages. A systematic in vivo description of the microstructural changes that characterize early stage ALS, and their subsequent development, is so far lacking. Recent advances in ultra-high field (7 T) MRI data modelling allow us to investigate cortical layers in vivo. Given the layer-specific and topographic signature of ALS pathology, we combined submillimetre structural 7 T MRI data (qT1, QSM), functional localizers of body parts (upper limb, lower limb, face) and layer modelling to systematically describe pathology in the primary motor cortex (M1), in 12 living ALS patients with reference to 12 matched controls. Longitudinal sampling was performed for a subset of patients. We calculated multimodal pathology maps for each layer (superficial layer, layer 5a, layer 5b, layer 6) of M1 to identify hot spots of demyelination, iron and calcium accumulation in different cortical fields. We show preserved mean cortical thickness and layer architecture of M1, despite significantly increased iron in layer 6 and significantly increased calcium in layer 5a and superficial layer, in patients compared to controls. The behaviourally first-affected cortical field shows significantly increased iron in L6 compared to other fields, while calcium accumulation is atopographic and significantly increased in the low myelin borders between cortical fields compared to the fields themselves. A subset of patients with longitudinal data shows that the low myelin borders are particularly disrupted and that calcium hot spots, but to a lesser extent iron hot spots, precede demyelination. Finally, we highlight that a very slow progressing patient (Patient P4) shows a distinct pathology profile compared to the other patients. Our data show that layer-specific markers of in vivo pathology can be identified in ALS patients with a single 7 T MRI measurement after first diagnosis, and that such data provide critical insights into the individual disease state. Our data highlight the non-topographic architecture of ALS disease spread and the role of calcium, rather than iron accumulation, in predicting future demyelination. We also highlight a potentially important role of low myelin borders, that are known to connect to multiple areas within the M1 architecture, in disease spread. Finally, the distinct pathology profile of a very-slow progressing patient (Patient P4) highlights a distinction between disease duration and progression. Our findings demonstrate the importance of in vivo histology imaging for the diagnosis and prognosis of neurodegenerative diseases such as ALS.}, } @article {pmid37815061, year = {2024}, author = {Zhang, X and Dai, L and Long, Y and Chen, X and Alhafi, MAK}, title = {Healthcare costs for patients with rare diseases: Evidence from China.}, journal = {The International journal of health planning and management}, volume = {39}, number = {1}, pages = {48-61}, doi = {10.1002/hpm.3713}, pmid = {37815061}, issn = {1099-1751}, support = {21Y012//Hubei Provincial Department of Education Project/ ; }, mesh = {Humans ; *Insurance, Health ; Rare Diseases/therapy ; *Amyotrophic Lateral Sclerosis ; Health Care Costs ; Health Expenditures ; China ; }, abstract = {OBJECTIVE: Rare diseases cause a huge financial burden to countless patients and families. It is an important public health issue that requires widespread attention. This study analyzes medical expenses composition and the change in trends of out-of-pocket (OOP) expenses for patients with Amyotrophic lateral sclerosis (ALS) and explores the factors influencing these changes.

METHODS: Data were obtained from the Chinese Medical Insurance Department database from 2018 to 2020, including 857 patients with ALS in 60 cities across 30 provinces. We used descriptive methods to analyse the baseline characteristics and medical expenses of outpatients and inpatients with ALS. And we used quantile regression to analyse the differences in patient OOP ratio and the factors influencing them.

RESULTS: In China, 80.3% of ALS patients chose tertiary hospitals, with an annual direct medical cost of 11,339.7 RMB per patient and an OOP ratio of 41.6%. The annual medical cost for outpatients was 345.1 RMB per patient, with an OOP ratio of 36.7%. The annual medical cost for inpatients was 28,139.8 RMB per patient, with an OOP ratio of 41.7%. Compared to outpatients, inpatients had higher medical costs but lower actual reimbursement rates. The OOP ratio of ALS patients decreased, then increased over time. And the OOP ratio was influenced by medical institution, medical insurance, and age (p < 0.05). Patients who chose tertiary hospitals, those who were covered by the urban resident basic medical insurance and younger patients had relatively higher OOP ratio.

CONCLUSION: In recent years, although China has begun to pay attention to the rights and interests of patients with rare diseases, the government has provided some healthcare security to patients with rare diseases. However, the level of medical insurance coverage was still low, the equity of protection was still insufficient and the financial burden on patients was high. Therefore, the government should further improve the healthcare system to provide full life-cycle and affordable healthcare services to patients with rare diseases.}, } @article {pmid37814924, year = {2023}, author = {Spiliopoulos, KC and Lykouras, D and Veltsista, D and Skaramagkas, V and Karkoulias, K and Tzouvelekis, A and Chroni, E}, title = {The utility of diaphragm ultrasound thickening indices for assessing respiratory decompensation in amyotrophic lateral sclerosis.}, journal = {Muscle & nerve}, volume = {68}, number = {6}, pages = {850-856}, doi = {10.1002/mus.27980}, pmid = {37814924}, issn = {1097-4598}, mesh = {Humans ; Diaphragm/diagnostic imaging ; *Amyotrophic Lateral Sclerosis/complications/diagnostic imaging ; *Noninvasive Ventilation ; *Respiratory Insufficiency/diagnostic imaging/etiology ; Ultrasonography ; }, abstract = {INTRODUCTION/AIMS: Amyotrophic lateral sclerosis (ALS) leads to diaphragmatic weakness at some point during its course, which is a major cause of respiratory insufficiency. The aim of this study was to evaluate ultrasound-based measures for assessing the diaphragmatic competency and the need for ventilatory support.

METHODS: Twenty-six subjects with ALS and 12 healthy controls were enrolled. All participants underwent B-mode diaphragm ultrasound (DUS). Diaphragm thickness and thickening indices were recorded. In the subjects with ALS, further assessments included functional scales and spirometry. We investigated the diagnostic accuracy of DUS thickening indices in predicting diaphragmatic dysfunction and the correlation between clinical, spirometric, and DUS data.

RESULTS: Significant relationships were found between forced vital capacity and all diaphragmatic thickening indices. Similarly, all diaphragmatic thickening indices correlated with both Milano Torino staging and disease progression rate. Only thickening fraction (TFdi) correlated with score on the revised ALS Functional Rating Scale (r = 0.459, P = .024). TFdi had better accuracy in predicting diaphragmatic dysfunction (area under the curve [AUC] = 0.839, 95% confidence interval [CI] 0.643 to 0.953) and the need for initiation of noninvasive ventilation (NIV) (AUC = 0.989, 95% CI 0.847 to 1.000) compared with the other indices. A TFdi cut-off point of 0.50 was a sensitive threshold to consider NIV.

DISCUSSION: DUS successfully identifies diaphragmatic dysfunction in ALS, being a valuable accessory modality for investigating respiratory symptoms. TFdi was found to be the most useful DUS index, which encourages further investigation.}, } @article {pmid37814618, year = {2023}, author = {Li, B and Zhang, W and Zhong, S and Pan, J and Wang, X and Zou, H and Dou, X}, title = {Short-term outcome of plasma adsorption therapy in amyotrophic lateral sclerosis.}, journal = {Journal of medical biochemistry}, volume = {42}, number = {3}, pages = {401-406}, pmid = {37814618}, issn = {1452-8258}, abstract = {BACKGROUND: To observe the short-term outcome of plasma adsorption PA therapy in amyotrophic lateral sclerosis (ALS).

METHODS: 28 cases of als patients were recruited in this study, of which 20 were male and 8 were female with a mean age of 53.21±9.07 years and the average course of 33±23.35 months. The clinical manifestations were limb weakness (N=27), muscular atrophy (N=27), muscular tremor (N=5), dysphagia (N=12) and dysarthria (N=12). The clinical data of the patients recruited were graded by Amyotrophic Lateral Sclerosis Functional Rating Scale Revised (ALSFRSR) : <10 (N=1), 11-20 (N=4), 21-30 (N=6), 31-40 (N=12), >40 (N=5). All patients received PA therapy once a week for three successive times after examining the conditions of blood coagulation and virus infection. PA therapy was supplemented with neurotrophic therapy meanwhile. All patients' clinical manifestations and scores of ALSFRSR before treatment and one week after treatment were evaluated and compared. The levels of serum superoxide dismutase (SOD), interleukin-10 (IL-10), serum creatine kinase (CK) and lactate dehydrogenase (LDH) before and after treatment were compared.

RESULTS: After PA therapy, 14 patients have improved obviously in muscle strength, 4 patients in hypermyotonia partially, 3 patients in muscular tremor, 5 patients in dysarthria, 3 patients in salivation to some extent and 2 patients in swallowing function. The score of ALSFRSR after PA treatment (31.89±10.36) was remarkably higher than that before PA treatment (30.68±10.52) (P<0.01). The levels of SOD (155.10±21.87 IU/L) and IL-10 (138.06±185.88 pg/mL) after PA treatment were significantly higher than the levels before PA treatment (143.08.3±19.16 IU/L and 46.34±75.31 pg/mL, respectively) (P<0.05). The levels of CK (168.86±113.50 IU/L) and LDH (152.07±32.65 IU/L) after PA treatment were significantly lower than the levels before PA treatment (356.68±250.30 IU/L and 181.36±33.74 IU/L respectively) (P<0.01). At the end of follow-up period (November, 2019), five patients died of respiratory failure 16-21 months after PA treatment and two patents died of respiratory infection 15-20 months after PA treatment. 7 patients were still alive. The score of ALSFRS-R of these patients who survived at the end of follow-up (13.00±13.37) were significantly lower than before PA treatment (36.71±8.56) (P<0.05) and after PA treatment (38.14±8.82) (P<0.05).

CONCLUSIONS: Plasma adsorption (PA) therapy has shortterm therapeutic effects on als. The effects might be attributed to the anti-oxygen free radical effect by increasing SOD level and the anti-inflammation effect by increasing IL-10 level. As the efficacy of PA therapy was obtained in a small sample size and short follow-up period, the longterm observation of PA efficacy in treating als should be further investigated.}, } @article {pmid37814465, year = {2023}, author = {Fan, J and Li, Y and Niu, JW and Hu, N and Guan, YZ and Cui, LY and Liu, MS}, title = {Differentiation Between Amyotrophic Lateral Sclerosis and Mimics Using Quantitative Analysis of Fsciculation with Muscle Ultrasound.}, journal = {Chinese medical sciences journal = Chung-kuo i hsueh k'o hsueh tsa chih}, volume = {38}, number = {4}, pages = {265-272}, doi = {10.24920/004282}, pmid = {37814465}, issn = {1001-9294}, mesh = {Adult ; Humans ; *Amyotrophic Lateral Sclerosis/diagnostic imaging ; Fasciculation/diagnostic imaging ; *Radiculopathy ; Muscle, Skeletal/diagnostic imaging ; Ultrasonography/methods ; }, abstract = {Objective To determine the diagnostic accuracy of the intensity of fasciculation evaluated by muscle ultrasound in the differential diagnosis of amyotrophic lateral sclerosis (ALS). Methods We prospectively recruited patients who had ALS and neuropathy-radiculopathy attending Peking Union Medical College Hospital from 2017 to 2020. Healthy adults from a community were recruited as healthy controls. Muscle strength was assessed using the Medical Research Council (MRC) scale. At the first visit to the hospital, patients were assessed for maximal grade of fasciculations, total fasciculation score, and fasciculation grade in 16 muscle groups of bilateral upper and lower limbs using ultrasonography. The sensitivity and specificity of maximal grade of fasciculations, total fasciculation score, and fasciculation grade for the diagnosis of ALS were assessed by receiver operating characteristic analyses. Results The percentage of limb muscles with a maximal fasciculation grade higher than grade 2 in ALS patients and neuropathy-radiculopathy patients was 84.9% and 9.8%, respectively (χ[2] = 172.436, P < 0.01). Of the 16 limb muscles detected, the total fasciculation score [median (interquartile range)] was 29 (15, 41) in ALS patients and 3 (0, 8) in neuropathy-radiculopathy patients (Z = 9.642, P < 0.001). Remarkable fasciculations were seen in ALS patients whose muscles with a MRC score ranging from 2 to 4, followed by patients with MRC score 5, and then in those with MRC score 0 and 1. The sensitivity and specificity of total fasciculation score for diagnosis of ALS were 80.6% and 93.4%, respectively (cut-off value 14). In patients with ALS, for muscles with MRC score 4 and 5, the percentage of muscles with fasciculation grades ≥ 3 was 42.3% and 24.1% respectively, while in neuropathy-radiculopathy patients, the percentage for muscles with MRC score 4 and 5 was only 1.7% and 0, respectively. Conclusion A combined analysis of fasciculation intensity and MRC score of the limb muscles may be helpful for differential diagnosis of ALS.}, } @article {pmid37813308, year = {2023}, author = {Babazadeh, A and Rayner, SL and Lee, A and Chung, RS}, title = {TDP-43 as a therapeutic target in neurodegenerative diseases: Focusing on motor neuron disease and frontotemporal dementia.}, journal = {Ageing research reviews}, volume = {92}, number = {}, pages = {102085}, doi = {10.1016/j.arr.2023.102085}, pmid = {37813308}, issn = {1872-9649}, mesh = {Animals ; Humans ; *Amyotrophic Lateral Sclerosis/therapy ; DNA-Binding Proteins/metabolism ; *Frontotemporal Dementia/therapy ; *Motor Neuron Disease/therapy/pathology ; *Neurodegenerative Diseases/therapy ; }, abstract = {A common feature of adult-onset neurodegenerative diseases is the presence of characteristic pathological accumulations of specific proteins. These pathological protein depositions can vary in their protein composition, cell-type distribution, and intracellular (or extracellular) location. For example, abnormal cytoplasmic protein deposits which consist of the TDP-43 protein are found within motor neurons in patients with amyotrophic lateral sclerosis (ALS, a common form of motor neuron disease) and frontotemporal dementia (FTD). The presence of these insoluble intracellular TDP-43 inclusions suggests that restoring TDP-43 homeostasis represents a potential therapeutical strategy, which has been demonstrated in alleviating neurodegenerative symptoms in cell and animal models of ALS/FTD. We have reviewed the mechanisms that lead to disrupted TDP-43 homeostasis and discussed how small molecule-based therapies could be applied in modulating these mechanisms. This review covers recent advancements and challenges in small molecule-based therapies that could be used to clear pathological forms of TDP-43 through various protein homeostasis mechanisms and advance the way towards finding effective therapeutical drug discoveries for neurodegenerative diseases characterized by TDP-43 proteinopathies, especially ALS and FTD. We also consider the wider insight of these therapeutic strategies for other neurodegenerative diseases.}, } @article {pmid37813148, year = {2023}, author = {Heidet, M and Benjamin Leung, KH and Bougouin, W and Alam, R and Frattini, B and Liang, D and Jost, D and Canon, V and Deakin, J and Hubert, H and Christenson, J and Vivien, B and Chan, T and Cariou, A and Dumas, F and Jouven, X and Marijon, E and Bennington, S and Travers, S and Souihi, S and Mermet, E and Freyssenge, J and Arrouy, L and Lecarpentier, E and Derkenne, C and Grunau, B}, title = {Improving EMS response times for out-of-hospital cardiac arrest in urban areas using drone-like vertical take-off and landing air ambulances: An international, simulation-based cohort study.}, journal = {Resuscitation}, volume = {193}, number = {}, pages = {109995}, doi = {10.1016/j.resuscitation.2023.109995}, pmid = {37813148}, issn = {1873-1570}, mesh = {Adult ; Humans ; *Cardiopulmonary Resuscitation ; Cohort Studies ; *Air Ambulances ; *Out-of-Hospital Cardiac Arrest/therapy ; Reaction Time ; Unmanned Aerial Devices ; *Emergency Medical Services ; }, abstract = {BACKGROUND: Advances in vertical take-off and landing (VTOL) technologies may enable drone-like crewed air ambulances to rapidly respond to out-of-hospital cardiac arrest (OHCA) in urban areas. We estimated the impact of incorporating VTOL air ambulances on OHCA response intervals in two large urban centres in France and Canada.

METHODS: We included adult OHCAs occurring between Jan. 2017-Dec. 2018 within Greater Paris in France and Metro Vancouver in Canada. Both regions utilize tiered OHCA response with basic (BLS)- and advanced life support (ALS)-capable units. We simulated incorporating 1-2 ALS-capable VTOL air ambulances dedicated to OHCA response in each study region, and computed time intervals from call reception by emergency medical services (EMS) to arrival of the: (1) first ALS unit ("call-to-ALS arrival interval"); and (2) first EMS unit ("call-to-first EMS arrival interval").

RESULTS: There were 6,217 OHCAs included during the study period (3,760 in Greater Paris and 2,457 in Metro Vancouver). Historical median call-to-ALS arrival intervals were 21 min [IQR 16-29] in Greater Paris and 12 min [IQR 9-17] in Metro Vancouver, while median call-to-first EMS arrival intervals were 11 min [IQR 8-14] and 7 min [IQR 5-8] respectively. Incorporating 1-2 VTOL air ambulances improved median call-to-ALS arrival intervals to 7-9 min and call-to-first EMS arrival intervals to 6-8 min in both study regions (all P < 0.001).

CONCLUSION: VTOL air ambulances dedicated to OHCA response may improve EMS response intervals, with substantial improvements in ALS response metrics.}, } @article {pmid37812352, year = {2023}, author = {Salemi, M and Mandarà, LGM and Salluzzo, MG and Schillaci, FA and Castiglione, R and Cordella, A and Iorio, R and Perrotta, CS and Ferri, R and Romano, C}, title = {NGS study in a sicilian case series with a genetic diagnosis for Gerstmann-Sträussler-Scheinker syndrome (PRNP, p.P102L).}, journal = {Molecular biology reports}, volume = {50}, number = {11}, pages = {9715-9720}, pmid = {37812352}, issn = {1573-4978}, support = {(RC 2773804)//Ministero della Salute/ ; }, mesh = {Animals ; Humans ; *Gerstmann-Straussler-Scheinker Disease/diagnosis/genetics/metabolism ; *Prions/genetics ; Prion Proteins/genetics ; Mutation/genetics ; High-Throughput Nucleotide Sequencing ; }, abstract = {BACKGROUND: Gerstmann Sträussler Scheinker (GSS) is an inherited, invariably fatal prion disease. Like other human prion diseases, GSS is caused by missense mutations in the prion protein (PrP) gene (PRNP), and by the formation and overtime accumulation of the misfolded, pathogenic scrapie PrP (PrPSc). The first mutation identified in the PRNP gene, and the one blamed as the main cause of the disease, is c.C305T:p.P102L.

METHODS AND RESULTS: The Sanger sequencing method was performed on the PRNP gene for the detection of c.C305T:p.P102L mutations in a cohort of 10 subjects; moreover, a study was carried out, using Next Generation Sequencing (NGS), by sequencing a group of genes related to amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), movement disorders and dementia which show a phenotypic profile similar to that of GSS. The results obtained from the study using NGS indicate the potential role of other genetic variants which could contribute to the various GSS phenotypes.

CONCLUSIONS: In conclusion, we highlight the large clinical variability in subjects presenting with GSS and p.P102L, as well as the hypothesis that the mutation in PrP codon 102 alone is not sufficient to trigger the cardinal clinical signs of the disease; furthermore, we do not exclude the possibility that further genetic variants play a decisive role in the aspects of the various phenotypes with which GSS manifests itself.}, } @article {pmid37811740, year = {2023}, author = {Grossschaedl, K and Vallant, C and Dernoscheg, MT and Richtig, M and Öllinger, A and Balakirski, G and Wilsmann-Theis, D and Nguyen, VA and Weinlich, G and Tsiogka, A and Koelblinger, P and Scheffel, J and Richtig, E and Richtig, G}, title = {[Verwendung und Nutzen des Internets als Informationsquelle für Erkrankungen und Therapien in der Dermatologie: Usage and benefit of the Internet as a source of information on disease and therapy in dermatology].}, journal = {Journal der Deutschen Dermatologischen Gesellschaft = Journal of the German Society of Dermatology : JDDG}, volume = {21}, number = {11}, pages = {1383-1386}, doi = {10.1111/ddg.15199_g}, pmid = {37811740}, issn = {1610-0387}, } @article {pmid37810917, year = {2023}, author = {Carrera-Juliá, S and Estrela, JM and Zacarés, M and Navarro, MÁ and Vega-Bello, MJ and de la Rubia Ortí, JE and Moreno, ML and Drehmer, E}, title = {Effect of the Mediterranean diet supplemented with nicotinamide riboside and pterostilbene and/or coconut oil on anthropometric variables in amyotrophic lateral sclerosis. A pilot study.}, journal = {Frontiers in nutrition}, volume = {10}, number = {}, pages = {1232184}, pmid = {37810917}, issn = {2296-861X}, abstract = {Amyotrophic Lateral Sclerosis (ALS) is a chronic and progressive neurodegenerative disease that causes the death of motor neurons and alters patients' body composition. Supplementation with the antioxidants nicotinamide riboside (NR) and pterostilbene (PTER) can combat associated oxidative stress. Additionally, coconut oil is an alternative energy substrate that can address mitochondrial dysfunction. The aim of the present study is to assess the impact of a Mediterranean Diet supplemented with NR and PTER and/or with coconut oil on the anthropometric variables of patients with ALS. A prospective, mixed, randomized, analytical and experimental pilot study in humans was performed through a clinical trial (registered with ClinicalTrials.gov under number NCT03489200) with pre- and post-intervention assessments. The sample was made up of 40 subjects categorized into four study groups (Control, Antioxidants, Coconut oil, and Antioxidants + Coconut oil). Pre- and post-intervention anthropometric assessments were carried out to determine the following data: weight, percentage of fat and muscle mass, skinfolds, body perimeters, Body Mass Index (BMI), Waste-to-Hip Index (WHI) and Waist-Height Ratio (WHR). Compared to the Control group, GAx significantly increased muscle mass percentage and decreased fat mass percentage, triceps, iliac crest, and abdominal skinfolds. GCoco significantly increased muscle mass percentage and decreased fat mass percentage, subscapular skinfolds, and abdominal skinfolds. GAx + coco significantly increased muscle mass percentage and decreased abdominal skinfolds. Therefore, our results suggest that the Mediterranean Diet supplemented with NR and PTER and the Mediterranean Diet supplemented with coconut oil (ketogenic diet) are the two nutritional interventions that have reported the greatest benefits, at anthropometric level.}, } @article {pmid37809062, year = {2023}, author = {Akhtar, M and Basher, SR and Nizam, NN and Hossain, L and Bhuiyan, TR and Qadri, F and Lundgren, A}, title = {T helper cell responses in adult diarrheal patients following natural infection with enterotoxigenic Escherichia coli are primarily of the Th17 type.}, journal = {Frontiers in immunology}, volume = {14}, number = {}, pages = {1220130}, pmid = {37809062}, issn = {1664-3224}, mesh = {Adult ; Humans ; Antibodies, Bacterial ; *Bacterial Toxins ; Diarrhea ; *Enterotoxigenic Escherichia coli ; Enterotoxins ; Immunoglobulin A ; Interleukin-17 ; Leukocytes, Mononuclear/chemistry ; Th17 Cells ; }, abstract = {BACKGROUND: Infection with enterotoxigenic Escherichia coli (ETEC) gives rise to IgA antibodies against both the heat labile toxin (LT) and colonization factors (CFs), which are considered to synergistically protect against ETEC diarrhea. Since the development of ETEC-specific long lived plasma cells and memory B cells is likely to be dependent on T helper (Th) cells, we investigated if natural ETEC diarrhea elicits ETEC-specific Th cells and their relation to IgA responses.

METHODS: Th cell subsets were analyzed in adult Bangladeshi patients hospitalized due to ETEC diarrhea by flow cytometric analysis of peripheral blood mononuclear cells (PBMCs) isolated from blood collected day 2, 7, 30 and 90 after hospitalization as well as in healthy controls. The LT- and CF-specific Th responses were determined by analysis of IL-17A and IFN-γ in antigen stimulated PBMC cultures using ELISA. ETEC-specific IgA secreted by circulating antibody secreting cells (plasmablasts) were analyzed by using the antibodies in lymphocyte supernatants (ALS) ELISA-based method and plasma IgA was also measured by ELISA.

RESULTS: ETEC patients mounted significant ALS and plasma IgA responses against LTB and CFs on day 7 after hospitalization. ETEC patients had significantly elevated proportions of memory Th cells with a Th17 phenotype (CCR6+CXCR3-) in blood compared to controls, while frequencies of Th1 (CCR6-CXCR3+) or Th2 (CCR6-CXCR3-) cells were not increased. Antigen stimulation of PBMCs revealed IL-17A responses to LT, most clearly observed after stimulation with double mutant heat labile toxin (dmLT), but also with LT B subunit (LTB), and to CS6 in samples from patients with LT+ or CS6+ ETEC bacteria. Some individuals also mounted IFN-γ responses to dmLT and LTB. Levels of LTB specific IgA antibodies in ALS, but not plasma samples correlated with both IL-17A (r=0.5, p=0.02) and IFN-γ (r=0.6, p=0.01) responses to dmLT.

CONCLUSIONS: Our results show that ETEC diarrhea induces T cell responses, which are predominantly of the Th17 type. The correlations between IL-17A and IFN-g and intestine-derived plasmablast responses support that Th responses may contribute to the development of protective IgA responses against ETEC infection. These observations provide important insights into T cell responses that need to be considered in the evaluation of advanced ETEC vaccine candidates.}, } @article {pmid37808871, year = {2024}, author = {Okekenwa, S and Tsai, M and Dooley, P and Wang, B and Comassio, P and Moreira, J and Kriefall, N and Martin, S and Morfini, G and Brady, S and Song, Y}, title = {Divergent Molecular Pathways for Toxicity of Selected Mutant C9ORF72-derived Dipeptide Repeats.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2023.09.28.558663}, pmid = {37808871}, issn = {2692-8205}, abstract = {Expansion of a hexanucleotide repeat in a noncoding region of the C9ORF72 gene is responsible for a significant fraction of Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD) cases, but mechanisms linking mutant gene products to neuronal toxicity remain debatable. Pathogenesis was proposed to involve the production of toxic RNA species and/or accumulation of toxic dipeptide repeats (DPRs) but distinguishing between these mechanisms has been challenging. In this study, we first use complementary model systems for analyzing pathogenesis in adult-onset neurodegenerative diseases to characterize the pathogenicity of DPRs produced by Repeat Associated Non-ATG translation of C9ORF72 in specific cellular compartments: isolated axoplasm and giant synapse from the squid. Results showed selective axonal and presynaptic toxicity of GP-DPRs, independent of associated RNA. These effects involved a MAPK signaling pathway that affects fast axonal transport and synaptic function, a pathogenic mechanism shared with other mutant proteins associated with familial ALS, like SOD1 and FUS. In primary cultured neurons, GP but not other DPRs promote the "dying-back" axonopathy seen in ALS. Interestingly, GR- and PR-DPRs, which had no effect on axonal transport or synaptic transmission, were found to disrupt the nuclear membrane, promoting "dying-forward" neuropathy. All C9-DPR-mediated toxic effects observed in these studies are independent of whether the corresponding mRNAs contained hexanucleotide repeats or alternative codons. Finally, C9ORF72 human tissues confirmed a close association between GP and active P38 in degenerating motor neurons as well as GR-associated nuclear damage in the cortex. Collectively, our studies establish compartment-specific toxic effects of C9-DPRs associated with degeneration, suggesting that two independent pathogenic mechanisms may contribute to disease heterogeneity and/or synergize on disease progression in C9ORF72 patients with ALS and/or FTD symptoms.}, } @article {pmid37807882, year = {2023}, author = {Pereira-Elizeu, AV and de Ávila-Panisset, J and Rodrigues-da Silva, ML and da Silva-Paz, LP and da Costa-Cunha, K and da Silva, ML and Monsores, N}, title = {Factors associated with the time taken for diagnosis of amyotrophic lateral sclerosis (ALS) in Brazil. An online population-based inquiry.}, journal = {Revista de neurologia}, volume = {77}, number = {8}, pages = {177-183}, pmid = {37807882}, issn = {1576-6578}, mesh = {Male ; Humans ; Female ; Middle Aged ; *Amyotrophic Lateral Sclerosis/diagnosis ; Brazil ; }, abstract = {OBJECTIVE: This study evaluated factors associated with the time, in months, between the onset of symptoms and the diagnosis (time taken for diagnosis) of ALS for patients in Brazil, in the year 2014.

PATIENTS AND METHODS: An electronic questionnaire composed of 38 questions was developed and applied through internet-based social networks of patients. From the 210 replies, 194 were considered (86 from women, 108 from men). Most respondents were 51 to 60 years old. The Mann-Whitney test was used to compare the time taken for diagnosis between the strata of the sample.

RESULTS: The mean time taken for diagnosis was 14.21 (±16.87) months. There was a statistically significant difference only for higher education conditions (p = 0.009) and low education status (p = 0.042). There was no statistically significant difference between sexes, bulbar onset, age groups, and the presence of spouse, or 'partnership with ALS patients associations or exchange of experiences'.

CONCLUSION: These data suggest that the time taken for diagnosis of ALS is influenced by socioeconomic conditions that promote access to information and/or health services.}, } @article {pmid37807839, year = {2023}, author = {Paganoni, S and Quintana, M and Sherman, AV and Vestrucci, M and Wu, Y and Timmons, J and Cudkowicz, M and , }, title = {Analysis of sodium phenylbutyrate and taurursodiol survival effect in ALS using external controls.}, journal = {Annals of clinical and translational neurology}, volume = {10}, number = {12}, pages = {2297-2304}, pmid = {37807839}, issn = {2328-9503}, support = {//ALS Association/ ; //ALS Finding a Cure®/ ; //Amylyx Pharmaceuticals, Inc./ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy ; Phenylbutyrates/pharmacology/therapeutic use ; Survival Analysis ; Proportional Hazards Models ; }, abstract = {OBJECTIVE: Sodium phenylbutyrate and taurursodiol (PB and TURSO) was evaluated in amyotrophic lateral sclerosis (ALS) in the CENTAUR trial encompassing randomized placebo-controlled and open-label extension phases. On intent-to-treat (ITT) survival analysis, median overall survival (OS) was 4.8 months longer and risk of death 36% lower in those originally randomized to an initial 6-month double-blind period of PB and TURSO versus placebo. To estimate PB and TURSO treatment effect without placebo-to-active crossover, we performed a post hoc survival analysis comparing PB and TURSO-randomized participants from CENTAUR and a propensity score-matched, PB and TURSO-naïve external control cohort from the Pooled Resource Open-Access ALS Clinical Trials (PRO-ACT) database.

METHODS: Clinical trial control participants from the PRO-ACT database who met prespecified eligibility criteria were propensity score matched 1:1 with PB and TURSO-randomized CENTAUR participants using prognostically significant covariates in ALS.

RESULTS: Baseline characteristics including propensity score-matched covariates were generally well balanced between CENTAUR PB and TURSO (n = 89) and PRO-ACT external control (n = 85) groups. Estimated median (IQR) OS was 23.54 (14.56-39.32) months in the CENTAUR PB and TURSO group and 13.15 (9.83-19.20) months in the PRO-ACT external control group; hazard of death was 52% lower in the former group (hazard ratio, 0.48; 95% CI, 0.31-0.72; p = 0.00048).

INTERPRETATION: This analysis suggests potentially greater survival benefit with PB and TURSO in ALS without placebo-to-active crossover than seen on ITT analysis in CENTAUR. Analyses using well-matched external controls may provide additional context for evaluating survival effects in future ALS trials.}, } @article {pmid37807784, year = {2023}, author = {Barba, L and Otto, M and Abu-Rumeileh, S}, title = {The Underestimated Relevance of Alzheimer's Disease Copathology in Amyotrophic Lateral Sclerosis.}, journal = {Journal of Alzheimer's disease : JAD}, volume = {95}, number = {4}, pages = {1401-1404}, doi = {10.3233/JAD-230900}, pmid = {37807784}, issn = {1875-8908}, mesh = {Humans ; *Alzheimer Disease/diagnosis ; *Amyotrophic Lateral Sclerosis/diagnosis ; tau Proteins/cerebrospinal fluid ; Neurofilament Proteins/cerebrospinal fluid ; Biomarkers/cerebrospinal fluid ; *Cognitive Dysfunction ; Amyloid beta-Peptides/cerebrospinal fluid ; }, abstract = {Concomitant Alzheimer's disease (AD) pathology can be observed in approximately 10-15% of cases with amyotrophic lateral sclerosis (ALS). ALS-AD patients have a higher prevalence of amnestic cognitive disturbances, which may often precede motor symptoms. Cerebrospinal fluid (CSF) AD core biomarkers usually show no or slightly significant changes in ALS, whereas blood phosphorylated tau protein might be increased independently from AD copathology. Neurofilament proteins are consistently elevated in CSF and blood of ALS, but have been poorly investigated in ALS-AD. All these issues should be taken into account when using fluid biomarkers as inclusion criteria or secondary endpoints in clinical trials.}, } @article {pmid37807406, year = {2023}, author = {Anderson, G}, title = {Gut Microbiome and Circadian Interactions with Platelets Across Human Diseases, including Alzheimer's Disease, Amyotrophic Lateral Sclerosis, and Cancer.}, journal = {Current topics in medicinal chemistry}, volume = {23}, number = {28}, pages = {2699-2719}, doi = {10.2174/0115680266253465230920114223}, pmid = {37807406}, issn = {1873-4294}, mesh = {Humans ; *Melatonin/metabolism ; *Alzheimer Disease ; *Gastrointestinal Microbiome ; *Amyotrophic Lateral Sclerosis ; *Neoplasms ; Tumor Microenvironment ; }, abstract = {Platelets have traditionally been investigated for their role in clot formation in the course of cardiovascular diseases and strokes. However, recent work indicates platelets to be an integral aspect of wider systemic processes, with relevance to the pathophysiology of a host of diverse medical conditions, including neurodegenerative disorders and cancer. This article reviews platelet function and interactions with the gut microbiome and circadian systems, highlighting the role of the platelet mitochondrial melatonergic pathway in determining platelet activation, fluxes and plasticity. This provides a number of novel conceptualizations of platelet function and mode of interaction with other cell types, including in the pathoetiology and pathophysiology of diverse medical conditions, such as cancer, Alzheimer's disease, and amyotrophic lateral sclerosis. It is proposed that a platelet-gut axis allows platelets to contribute to many of the pathophysiological processes linked to gut dysbiosis and gut permeability. This is at least partly via platelet sphingosine- 1-phosphate release, which regulates enteric glial cells and lymphocyte chemotaxis, indicating an etiological role for platelets in a wide array of medical conditions linked to alterations in the gut microbiome. Platelets are also an important regulator of the various microenvironments that underpin most human medical conditions, including the tumor microenvironment, neurodegenerative diseases, and autoimmune disorders. Platelet serotonin release regulates the availability of the mitochondrial melatonergic pathway systemically, thereby being an important determinant of the dynamic metabolic interactions occurring across cell types that underpin the pathoetiology of many medical conditions. In addition, a number of novel and diverse future research directions and treatment implications are proposed.}, } @article {pmid37806880, year = {2024}, author = {Wang, L and Cao, W and Xi, MH and Li, Y}, title = {Appendectomy and the risk of neurodegenerative diseases: A two-sample Mendelian randomization study.}, journal = {Asian journal of surgery}, volume = {47}, number = {1}, pages = {673-674}, doi = {10.1016/j.asjsur.2023.09.170}, pmid = {37806880}, issn = {0219-3108}, mesh = {Humans ; *Neurodegenerative Diseases/genetics ; Mendelian Randomization Analysis ; Appendectomy ; Genetic Predisposition to Disease ; }, } @article {pmid37804508, year = {2023}, author = {Mamontova, EM and Clément, MJ and Sukhanova, MV and Joshi, V and Bouhss, A and Rengifo-Gonzalez, JC and Desforges, B and Hamon, L and Lavrik, OI and Pastré, D}, title = {FUS RRM regulates poly(ADP-ribose) levels after transcriptional arrest and PARP-1 activation on DNA damage.}, journal = {Cell reports}, volume = {42}, number = {10}, pages = {113199}, doi = {10.1016/j.celrep.2023.113199}, pmid = {37804508}, issn = {2211-1247}, mesh = {Humans ; *DNA Damage ; DNA Repair ; HeLa Cells ; Poly (ADP-Ribose) Polymerase-1/genetics/metabolism ; *Poly Adenosine Diphosphate Ribose/metabolism ; Poly(ADP-ribose) Polymerase Inhibitors ; *Poly(ADP-ribose) Polymerases/genetics/metabolism ; RNA Recognition Motif ; *RNA-Binding Protein FUS/genetics/metabolism ; }, abstract = {PARP-1 activation at DNA damage sites leads to the synthesis of long poly(ADP-ribose) (PAR) chains, which serve as a signal for DNA repair. Here we show that FUS, an RNA-binding protein, is specifically directed to PAR through its RNA recognition motif (RRM) to increase PAR synthesis by PARP-1 in HeLa cells after genotoxic stress. Using a structural approach, we also identify specific residues located in the FUS RRM, which can be PARylated by PARP-1 to control the level of PAR synthesis. Based on the results of this work, we propose a model in which, following a transcriptional arrest that releases FUS from nascent mRNA, FUS can be recruited by PARP-1 activated by DNA damage to stimulate PAR synthesis. We anticipate that this model offers new perspectives to understand the role of FET proteins in cancers and in certain neurodegenerative diseases such as amyotrophic lateral sclerosis.}, } @article {pmid37804412, year = {2024}, author = {Kusama-Eguchi, K and Tokui, Y and Minoura, A and Yanai, Y and Hirose, D and Furukawa, M and Kosuge, Y and Miura, M and Ohkoshi, E and Makino, M and Minagawa, K and Matsuzaki, K and Ogawa, Y and Watanabe, K and Ohsaki, A}, title = {2(3H)-Dihydrofranolactone metabolites from Pleosporales sp. NUH322 as anti-amyotrophic lateral sclerosis drugs.}, journal = {Journal of natural medicines}, volume = {78}, number = {1}, pages = {146-159}, pmid = {37804412}, issn = {1861-0293}, support = {12-021//A Grant from the Ministry of Education, Culture, Sports, Science, and Technology to promote 2001-multidisciplinary research projects/ ; 13-023//A Grant from the Ministry of Education, Culture, Sports, Science, and Technology to promote 2001-multidisciplinary research projects/ ; 22590088//Grant-in-Aid for Scientific Research/ ; }, mesh = {Mice ; Male ; Female ; Animals ; *Amyotrophic Lateral Sclerosis/drug therapy/genetics/metabolism ; Motor Neurons/metabolism ; Superoxide Dismutase-1/genetics/metabolism ; Mice, Transgenic ; Superoxide Dismutase/metabolism ; Spinal Cord/metabolism ; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid/metabolism ; Disease Models, Animal ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a devastating motor disease with limited treatment options. A domestic fungal extract library was screened using three assays related to the pathophysiology of ALS with the aim of developing a novel ALS drug. 2(3H)-dihydrofuranolactones 1 and 2, and five known compounds 3-7 were isolated from Pleosporales sp. NUH322 culture media, and their protective activity against the excitotoxicity of β-N-oxalyl-L-α,β-diaminopropionic acid (ODAP), an α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamatergic agonist, was evaluated under low mitochondrial glutathione levels induced by ethacrynic acid (EA) and low sulfur amino acids using our developed ODAP-EA assay. Additional assays evaluated the recovery from cytotoxicity caused by transfected SOD1-G93A, an ALS-causal gene, and the inhibitory effect against reactive oxygen species (ROS) elevation. The structures of 1 and 2 were elucidated using various spectroscopic methods. We synthesized 1 from D-ribose, and confirmed the absolute structure. Isolated and synthesized 1 displayed higher ODAP-EA activities than the extract and represented its activity. Furthermore, 1 exhibited protective activity against SOD1-G93A-induced toxicity. An ALS mouse model, SOD1-G93A, of both sexes, was treated orally with 1 at pre- and post-symptomatic stages. The latter treatment significantly extended their lifespan (p = 0.03) and delayed motor deterioration (p = 0.001-0.01). Our result suggests that 1 is a promising lead compound for the development of ALS drugs with a new spectrum of action targeting both SOD1-G93A proteopathy and excitotoxicity through its action on the AMPA-type glutamatergic receptor.}, } @article {pmid37803257, year = {2023}, author = {Genuis, SK and Luth, W and Weber, G and Bubela, T and Johnston, WS}, title = {Asynchronous online focus groups for research with people living with amyotrophic lateral sclerosis and family caregivers: usefulness, acceptability and lessons learned.}, journal = {BMC medical research methodology}, volume = {23}, number = {1}, pages = {222}, pmid = {37803257}, issn = {1471-2288}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy ; Caregivers ; Focus Groups ; Travel ; Travel-Related Illness ; }, abstract = {BACKGROUND: People with amyotrophic lateral sclerosis (ALS) face disability- and travel-related barriers to research participation. We investigate the usefulness and acceptability of asynchronous, online focus groups (AOFGs) for research involving people affected by ALS (patients and family caregivers) and outline lessons learned.

METHODS: The ALS Talk Project, consisting of seven AOFGs and 100 participants affected by ALS, provided context for this investigation. Hosted on the secure itracks Board™ platform, participants interacted in a threaded web forum structure. Moderators posted weekly discussion questions and facilitated discussion. Data pertaining to methodology, participant interaction and experience, and moderator technique were analyzed using itracks and NVivo 12 analytics (quantitative) and conventional content analysis and the constant-comparative approach (qualitative).

RESULTS: There was active engagement within groups, with post lengths averaging 111.48 words and a complex network of branching interactions between participants. One third of participant responses included individual reflections without further interaction. Participants affirmed their co-group members, offered practical advice, and discussed shared and differing perspectives. Moderators responded to all posts, indicating presence and probing answers. AOFGs facilitated qualitative and quantitative data-gathering and flexible response to unanticipated events. Although total participation fell below 50% after 10-12 weeks, participants valued interacting with peers in an inclusive, confidential forum. Participants used a variety of personal devices, browsers, and operating systems when interacting on the online platform.

CONCLUSIONS: This methodological examination of AOFGs for patient-centred investigations involving people affected by ALS demonstrates their usefulness and acceptability, and advances knowledge of online research methodologies. Lessons learned include: early identification of research goals and participant needs is critical to selecting an AOFG platform; although duration longer than 10-12 weeks may be burdensome in this population, participants were positive about AOFGs; AOFGs offer real world flexibility enabling response to research challenges and opportunities; and, AOGFs can effectively foster safe spaces for sharing personal perspectives and discussing sensitive topics. With moderators playing an important role in fostering engagement, AOFGs facilitated rich data gathering and promoted reciprocity by fostering the exchange of ideas and interaction between peers. Findings may have implications for research involving other neurologically impaired and/or medically vulnerable populations.}, } @article {pmid37802187, year = {2024}, author = {Weiss, BD}, title = {Role of health literacy screening in clinical practice-Response to Reddy et al's JAAD paper titled "Health literacy screening tools to identify patients at risk of misunderstanding wound care instructions after dermatologic surgery".}, journal = {Journal of the American Academy of Dermatology}, volume = {90}, number = {1}, pages = {e39}, doi = {10.1016/j.jaad.2023.07.1046}, pmid = {37802187}, issn = {1097-6787}, mesh = {Humans ; *Health Literacy ; Dermatologic Surgical Procedures/adverse effects ; }, } @article {pmid37801095, year = {2024}, author = {Gentile, F and Maranzano, A and Verde, F and Bettoni, V and Colombo, E and Doretti, A and Olivero, M and Scheveger, F and Colombrita, C and Bulgarelli, I and Spinelli, EG and Torresani, E and Messina, S and Maderna, L and Agosta, F and Morelli, C and Filippi, M and Silani, V and Ticozzi, N}, title = {The value of routine blood work-up in clinical stratification and prognosis of patients with amyotrophic lateral sclerosis.}, journal = {Journal of neurology}, volume = {271}, number = {2}, pages = {794-803}, pmid = {37801095}, issn = {1432-1459}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis ; Creatinine ; Chlorides ; Disease Progression ; Prognosis ; Biomarkers ; }, abstract = {BACKGROUND: There is an unmet need in amyotrophic lateral sclerosis (ALS) to provide specific biomarkers for the disease. Due to their easy availability, we aimed to investigate whether routine blood parameters provide useful clues for phenotypic classification and disease prognosis.

METHODS: We analyzed a large inpatient cohort of 836 ALS patients who underwent deep phenotyping with evaluation of the clinical and neurophysiological burden of upper (UMN) and lower (LMN) motor neuron signs. Disability and progression rate were measured through the revised ALS Functional Rating Scale (ALSFRS-R) and its changes during time. Cox regression analysis was performed to assess survival associations.

RESULTS: Creatinine significantly correlated with LMN damage (r = 0.38), active (r = 0.18) and chronic (r = 0.24) denervation and baseline ALSFRS-R (r = 0.33). Creatine kinase (CK), alanine (ALT) and aspartate (AST) transaminases correlated with active (r = 0.35, r = 0.27, r = 0.24) and chronic (r = 0.37, r = 0.20, r = 0.19) denervation, while albumin and C-reactive protein significantly correlated with LMN score (r = 0.20 and r = 0.17). Disease progression rate showed correlations with chloride (r = -0.19) and potassium levels (r = -0.16). After adjustment for known prognostic factors, total protein [HR 0.70 (95% CI 0.57-0.86)], creatinine [HR 0.86 (95% CI 0.81-0.92)], chloride [HR 0.95 (95% CI 0.92-0.99)], lactate dehydrogenase [HR 0.99 (95% CI 0.99-0.99)], and AST [HR 1.02 (95% CI 1.01-1.02)] were independently associated with survival.

CONCLUSIONS: Creatinine is a reliable biomarker for ALS, associated with clinical features, disability and survival. Markers of nutrition/inflammation may offer additional prognostic information and partially correlate with clinical features. AST and chloride could further assist in predicting progression rate and survival.}, } @article {pmid37800716, year = {2023}, author = {Shipley, PZ and Falkenstern, SK}, title = {Life Patterns of Family Caregivers of Patients With Amyotrophic Lateral Sclerosis.}, journal = {Nursing science quarterly}, volume = {36}, number = {4}, pages = {356-368}, doi = {10.1177/08943184231187903}, pmid = {37800716}, issn = {1552-7409}, mesh = {Humans ; Caregivers/psychology ; *Amyotrophic Lateral Sclerosis/psychology ; Adaptation, Psychological ; *Nursing Research ; Surveys and Questionnaires ; Family/psychology ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a terminal disease that greatly affects patients and the family caregivers who provide most of their care. Despite the psychological, physical, and financial strain placed on ALS caregivers, few research efforts have been directed to this caregiving phenomenon. The purpose of this research study, utilizing Newman's health as expanding consciousness as the theoretical framework and research method, was to advance understanding of the experience of ALS family caregivers for the advancement of nursing science. Nine patterns of the whole across all family caregivers emerged from the data, showing important implications for nursing research and practice.}, } @article {pmid37800457, year = {2023}, author = {Billings, JL and Hilton, JBW and Liddell, JR and Hare, DJ and Crouch, PJ}, title = {Fundamental Neurochemistry Review: Copper availability as a potential therapeutic target in progressive supranuclear palsy: Insight from other neurodegenerative diseases.}, journal = {Journal of neurochemistry}, volume = {167}, number = {3}, pages = {337-346}, doi = {10.1111/jnc.15978}, pmid = {37800457}, issn = {1471-4159}, mesh = {Humans ; *Supranuclear Palsy, Progressive/diagnosis/pathology ; Copper ; *Neurodegenerative Diseases/therapy ; Superoxide Dismutase-1 ; *Neurochemistry ; *Parkinson Disease/pathology ; }, abstract = {Since the first description of Parkinson's disease (PD) over two centuries ago, the recognition of rare types of atypical parkinsonism has introduced a spectrum of related PD-like diseases. Among these is progressive supranuclear palsy (PSP), a neurodegenerative condition that clinically differentiates through the presence of additional symptoms uncommon in PD. As with PD, the initial symptoms of PSP generally present in the sixth decade of life when the underpinning neurodegeneration is already significantly advanced. The causal trigger of neuronal cell loss in PSP is unknown and treatment options are consequently limited. However, converging lines of evidence from the distinct neurodegenerative conditions of PD and amyotrophic lateral sclerosis (ALS) are beginning to provide insights into potential commonalities in PSP pathology and opportunity for novel therapeutic intervention. These include accumulation of the high abundance cuproenzyme superoxide dismutase 1 (SOD1) in an aberrant copper-deficient state, associated evidence for altered availability of the essential micronutrient copper, and evidence for neuroprotection using compounds that can deliver available copper to the central nervous system. Herein, we discuss the existing evidence for SOD1 pathology and copper imbalance in PSP and speculate that treatments able to provide neuroprotection through manipulation of copper availability could be applicable to the treatment of PSP.}, } @article {pmid37798838, year = {2024}, author = {Shojaie, A and Al Khleifat, A and Opie-Martin, S and Sarraf, P and Al-Chalabi, A}, title = {Non-motor symptoms in amyotrophic lateral sclerosis.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {25}, number = {1-2}, pages = {61-66}, pmid = {37798838}, issn = {2167-9223}, support = {/WT_/Wellcome Trust/United Kingdom ; P30 AG066509/AG/NIA NIH HHS/United States ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/complications/diagnosis ; Quality of Life ; Pain/etiology ; Disease Progression ; }, abstract = {OBJECTIVE: While motor symptoms are well-known in ALS, non-motor symptoms are often under-reported and may have a significant impact on quality of life. In this study, we aimed to examine the nature and extent of non-motor symptoms in ALS.

METHODS: A 20-item questionnaire was developed covering the domains of autonomic function, sleep, pain, gastrointestinal disturbance, and emotional lability, posted online and shared on social media platforms to target people with ALS and controls.

RESULTS: A total of 1018 responses were received, of which 927 were complete from 506 people with ALS and 421 unaffected individuals. Cold limbs (p 1.66 × 10[-36)], painful limbs (p 6.14 × 10[-28]), and urinary urgency (p 4.70 × 10[-23]) were associated with ALS. People with ALS were more likely to report autonomic symptoms, pain, and psychiatric symptoms than controls (autonomic symptoms B = 0.043, p 6.10 × 10[-5], pain domain B = 0.18, p 3.72 × 10[-11] and psychiatric domain B = 0.173, p 1.32 × 10[-4]).

CONCLUSIONS: Non-motor symptoms in ALS are common. The identification and management of non-motor symptoms should be integrated into routine clinical care for people with ALS. Further research is warranted to investigate the relationship between non-motor symptoms and disease progression, as well as to develop targeted interventions to improve the quality of life for people with ALS.}, } @article {pmid37797839, year = {2024}, author = {Hooper, MJ and Veon, FL and Enriquez, GL and Nguyen, M and Grimes, CB and LeWitt, TM and Pang, Y and Case, S and Choi, J and Guitart, J and Burns, MB and Zhou, XA}, title = {Reply to Wu et al's US SEER analysis of sepsis in Black patients with CTCL.}, journal = {Journal of the American Academy of Dermatology}, volume = {90}, number = {2}, pages = {e79}, pmid = {37797839}, issn = {1097-6787}, support = {KL2 TR001424/TR/NCATS NIH HHS/United States ; }, mesh = {Humans ; *Lymphoma, T-Cell, Cutaneous ; SEER Program ; Black People ; *Sepsis/diagnosis/epidemiology ; *Skin Neoplasms/epidemiology ; }, } @article {pmid37797620, year = {2023}, author = {Yonekura, K and Maki-Yonekura, S and Takaba, K}, title = {Applications and limitations of electron 3D crystallography.}, journal = {Structure (London, England : 1993)}, volume = {31}, number = {11}, pages = {1328-1334}, doi = {10.1016/j.str.2023.09.007}, pmid = {37797620}, issn = {1878-4186}, mesh = {Crystallography/methods ; *Electrons ; Crystallography, X-Ray ; *Proteins/chemistry ; Microscopy, Electron, Transmission ; Peptides ; }, abstract = {Three-dimensional electron diffraction (3D ED) is a measurement and analysis technique in transmission electron microscopy that is used for determining atomic structures from small crystals. Diverse targets such as proteins, polypeptides, and organic compounds, whose crystals exist in aqueous solutions and organic solvents, or as dried powders, can be studied with 3D ED. We have been involved in the development of this technique, which can now rapidly process a large number of data collected through AI control, enabling efficient structure determination. Here, we introduce this method and describe our recent results. These include the structures and pathogenic mechanisms of wild-type and mutant polypeptides associated with the debilitating disease amyotrophic lateral sclerosis (ALS), the double helical structure of nanographene promoting nanofiber formation, and the structural properties of an organic semiconductor containing disordered regions. We also discuss the limitations and prospects of 3D ED compared to microcrystallography with X-ray free electron lasers.}, } @article {pmid37796272, year = {2023}, author = {Weber, S and Corcia, P and Viader, F}, title = {[Genetics of amyotrophic lateral sclerosis].}, journal = {La Revue du praticien}, volume = {73}, number = {7}, pages = {783-787}, pmid = {37796272}, issn = {2101-017X}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics ; Mutation ; }, abstract = {GENETICS OF AMYOTROPHIC LATERAL SCLEROSIS. Approximately 10 to 15% of people with amyotrophic lateral sclerosis (ALS) have a family history of the disease. In 2/3 of them, but also in 10% of subjects without any family history of ALS, a pathogenic genetic variant can be identified. Many genes are involved, the four main ones being C9orf72 (which can also be responsible for dementia), SOD1, TARDBP and FUS. ALS of genetic origin is almost always inherited in an autosomal dominant pattern. The progress made in recent years in the knowledge of the genetic forms of ALS has led to a better understanding of the pathophysiology of the disease and has opened up new therapeutic avenues, some of which are already being explored. For all these reasons, it is now recommended that all patients with ALS, whether familial or not, undergo a genetic investigation, with analyses appropriate to their age and family history. When a pathogenic variant is found, it can then be sought in at-risk relatives who so desire. These tests must follow legally mandated procedures and can only be conducted in a specialized ALS center under the supervision of a geneticist after a thorough discussion of the personal and family implications of the result and written consent from the patient.}, } @article {pmid37796077, year = {2023}, author = {Belenky, VV and Plakhotina, NA and Skoromets, AA and Dugaev, PP and Komantsev, VN and Leontiev, OV}, title = {[Diagnostic capabilities of spinal MR angiography and spinal MR tractography in a patient with motor neuron disease].}, journal = {Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova}, volume = {123}, number = {9}, pages = {111-115}, doi = {10.17116/jnevro2023123091111}, pmid = {37796077}, issn = {1997-7298}, mesh = {Adult ; Humans ; *Amyotrophic Lateral Sclerosis/pathology ; Magnetic Resonance Angiography ; *Motor Neuron Disease/diagnostic imaging ; Motor Neurons/pathology ; *Muscular Atrophy, Spinal ; Spinal Cord/diagnostic imaging ; }, abstract = {Motor neuron diseases (MND) include two main forms - amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA). A certain part of these diseases is hereditary, while etiology of sporadic cases remains unknown. Both entities are known to develop because of motoneurons damage. Difference between them lies in the state of the descending pyramidal pathways. The pyramidal pathways in SMA are intact, as brain pyramidal neurons are not affected, thus pathology of SMA is restricted to anterior horns of spinal cord. Meanwhile, most forms of ALS arise due to loss of both cerebral and spinal motoneurons, which, in addition to anterior horn lesion, leads to pyramidal descending pathways damage either in brain or in spinal cord. While pathological distinction between these two entities is clear and definite, the clinical difference remains obscure. We present the case of 41-year old patient with MND, in whom spinal MR tractography has revealed lateral columns to be intact that proves the utility of spinal MR tractography in differential diagnosis between ALS and SMA. Given that ischemic diseases of the spinal cord often occur with a clinical picture of MND, we also examined this patient using spinal MRI angiography, revealing a pronounced narrowing and tortuosity of the spinal arteries, complicated by occlusion of the right twelve intercostal artery.}, } @article {pmid37795580, year = {2024}, author = {Rodriguez, P and Blakely, RD}, title = {Sink or swim: Does a worm paralysis phenotype hold clues to neurodegenerative disease?.}, journal = {Journal of cellular physiology}, volume = {239}, number = {6}, pages = {e31125}, doi = {10.1002/jcp.31125}, pmid = {37795580}, issn = {1097-4652}, support = {22A01//Florida Department of Health Ed/ ; }, mesh = {Animals ; *Caenorhabditis elegans/genetics ; *Neurodegenerative Diseases/genetics ; *Phenotype ; Humans ; *Disease Models, Animal ; Caenorhabditis elegans Proteins/genetics/metabolism ; Paralysis/genetics ; Swimming ; Signal Transduction/genetics ; Dopamine/metabolism ; }, abstract = {Receiving a neurodegenerative disease (NDD) diagnosis, such as Alzheimer's disease, Parkinson's disease, Huntington's disease, or amyotrophic lateral sclerosis, is devastating, particularly given the limited options for treatment. Advances in genetic technologies have allowed for efficient modeling of NDDs in animals and brought hope for new disease-modifying medications. The complexity of the mammalian brain and the costs and time needed to identify and develop therapeutic leads limits progress. Modeling NDDs in invertebrates, such as the fruit fly Drosophila melanogaster and the nematode Caenorhabditis elegans, offers orders of magnitude increases in speed of genetic analysis and manipulation, and can be pursued at substantially reduced cost, providing an important, platform complement and inform research with mammalian NDD models. In this review, we describe how our efforts to exploit C. elegans for the study of neural signaling and health led to the discovery of a paralytic phenotype (swimming-induced paralysis) associated with altered dopamine signaling and, surprisingly, to the discovery of a novel gene and pathway whose dysfunction in glial cells triggers neurodegeneration. Research to date on swip-10 and its putative mammalian ortholog MBLAC1, suggests that a tandem analysis will offer insights into NDD mechanisms and insights into novel, disease-modifying therapeutics.}, } @article {pmid37795273, year = {2023}, author = {Venediktov, AA and Bushueva, OY and Kudryavtseva, VA and Kuzmin, EA and Moiseeva, AV and Baldycheva, A and Meglinski, I and Piavchenko, GA}, title = {Closest horizons of Hsp70 engagement to manage neurodegeneration.}, journal = {Frontiers in molecular neuroscience}, volume = {16}, number = {}, pages = {1230436}, pmid = {37795273}, issn = {1662-5099}, abstract = {Our review seeks to elucidate the current state-of-the-art in studies of 70-kilodalton-weighed heat shock proteins (Hsp70) in neurodegenerative diseases (NDs). The family has already been shown to play a crucial role in pathological aggregation for a wide spectrum of brain pathologies. However, a slender boundary between a big body of fundamental data and its implementation has only recently been crossed. Currently, we are witnessing an anticipated advancement in the domain with dozens of studies published every month. In this review, we briefly summarize scattered results regarding the role of Hsp70 in the most common NDs including Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). We also bridge translational studies and clinical trials to portray the output for medical practice. Available options to regulate Hsp70 activity in NDs are outlined, too.}, } @article {pmid37795262, year = {2023}, author = {Lin, TJ and Cheng, KC and Wu, LY and Lai, WY and Ling, TY and Kuo, YC and Huang, YH}, title = {Corrigendum: Potential of cellular therapy for ALS: current strategies and future prospects.}, journal = {Frontiers in cell and developmental biology}, volume = {11}, number = {}, pages = {1292681}, doi = {10.3389/fcell.2023.1292681}, pmid = {37795262}, issn = {2296-634X}, abstract = {[This corrects the article DOI: 10.3389/fcell.2022.851613.].}, } @article {pmid37794802, year = {2024}, author = {Din Abdul Jabbar, MA and Guo, L and Guo, Y and Simmons, Z and Pioro, EP and Ramasamy, S and Yeo, CJJ}, title = {Describing and characterising variability in ALS disease progression.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {25}, number = {1-2}, pages = {34-45}, doi = {10.1080/21678421.2023.2260838}, pmid = {37794802}, issn = {2167-9223}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis ; Disease Progression ; }, abstract = {BACKGROUND, OBJECTIVES: Decrease in the revised ALS Functional Rating Scale (ALSFRS-R) score is currently the most widely used measure of disease progression. However, it does not sufficiently encompass the heterogeneity of ALS. We describe a measure of variability in ALSFRS-R scores and demonstrate its utility in disease characterization.

METHODS: We used 5030 ALS clinical trial patients from the Pooled Resource Open-Access ALS Clinical Trials database to calculate variability in disease progression employing a novel measure and correlated variability with disease span. We characterized the more and less variable populations and designed a machine learning model that used clinical, laboratory and demographic data to predict class of variability. The model was validated with a holdout clinical trial dataset of 84 ALS patients (NCT00818389).

RESULTS: Greater variability in disease progression was indicative of longer disease span on the patient-level. The machine learning model was able to predict class of variability with accuracy of 60.1-72.7% across different time periods and yielded a set of predictors based on clinical, laboratory and demographic data. A reduced set of 16 predictors and the holdout dataset yielded similar accuracy.

DISCUSSION: This measure of variability is a significant determinant of disease span for fast-progressing patients. The predictors identified may shed light on pathophysiology of variability, with greater variability in fast-progressing patients possibly indicative of greater compensatory reinnervation and longer disease span. Increasing variability alongside decreasing rate of disease progression could be a future aim of trials for faster-progressing patients.}, } @article {pmid37794794, year = {2024}, author = {Goyal, NA and Bonar, K and Savic, N and Beau Lejdstrom, R and Wright, J and Mellor, J and McDermott, C}, title = {Misdiagnosis of amyotrophic lateral sclerosis in clinical practice in Europe and the USA: a patient chart review and physician survey.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {25}, number = {1-2}, pages = {16-25}, doi = {10.1080/21678421.2023.2260808}, pmid = {37794794}, issn = {2167-9223}, mesh = {Humans ; Adolescent ; *Amyotrophic Lateral Sclerosis/diagnosis/epidemiology/therapy ; Cross-Sectional Studies ; Europe/epidemiology ; *Physicians ; Diagnostic Errors ; }, abstract = {OBJECTIVE: Delays in amyotrophic lateral sclerosis (ALS) diagnosis can result in compromised disease management and unnecessary costs. We examined the extent of ALS misdiagnosis in the US and Europe.

METHODS: Data were collected via the Adelphi ALS Disease Specific Programme™, a cross-sectional survey of physicians and a medical chart review of their consulting patients with ALS in France, Germany, Italy, Spain, the UK (EU5), and the US. Between July 2020 and March 2021, eligible physicians (primary speciality neurology, active involvement in managing patients with ALS) abstracted data from patients (≥18 years old) with confirmed ALS.

RESULTS: Overall, 138 physicians completed the survey (EU5 107, US 31), with data reviewed from 795 patient medical charts (EU5 568, US 227); 278 (35.0%) patients (EU5 183 [32.2%], US 95 [41.9%]) had received ≥1 initial misdiagnosis based on symptoms later attributed to ALS. Mean (SD) time from symptom onset to first healthcare professional consultation was 3.8 (5.2) months (EU5 4.3 [4.8] months, US 2.6 [5.8] months). Mean (SD) time from symptom onset to ALS diagnosis was 8.2 (12.5) months (EU5 9.6 [14.0] months, US 5.0 [6.8] months) and increased to 10.4 (17.9) for patients with a misdiagnosis (compared with 6.9 [7.2] for patients with no misdiagnosis). Physician-identified barriers to timely ALS diagnosis included the similarity of symptoms to other conditions and delayed referral to neurologists.

CONCLUSIONS: Misdiagnosis of ALS is frequent, with a protracted diagnostic pathway. Targeted education of patients and physicians about signs and symptoms and benefits of prompt referral to multidisciplinary care are needed.}, } @article {pmid37793650, year = {2024}, author = {Mori, F and Yasui, H and Miki, Y and Kon, T and Arai, A and Kurotaki, H and Tomiyama, M and Wakabayashi, K}, title = {Colocalization of TDP-43 and stress granules at the early stage of TDP-43 aggregation in amyotrophic lateral sclerosis.}, journal = {Brain pathology (Zurich, Switzerland)}, volume = {34}, number = {2}, pages = {e13215}, pmid = {37793650}, issn = {1750-3639}, support = {21K07452//Japan Society for the Promotion of Science/ ; 22H02948//Japan Society for the Promotion of Science/ ; 23K06802//Japan Society for the Promotion of Science/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/pathology ; Anterior Horn Cells/pathology ; Cytoplasm ; DNA-Binding Proteins ; Stress Granules ; }, abstract = {TDP-43 aggregates (skeins and round inclusions [RIs]) are frequent histopathological features of amyotrophic lateral sclerosis (ALS). We have shown that diffuse punctate cytoplasmic staining (DPCS) is the earliest pathologic manifestation of TDP-43 in ALS, corresponding to nonfibrillar TDP-43 located in the rough endoplasmic reticulum. Previous in vitro studies have suggested that TDP-43 inclusions may be derived from stress granules (SGs). Therefore, we investigated the involvement of SGs in the formation of TDP-43 inclusions. Formalin-fixed spinal cords of six ALS patients with a disease duration of less than 1 year (short duration), eight patients with a disease duration of 2-5 years (standard duration), and five normal controls were subjected to histopathological examination using antibodies against an SG marker, HuR. In normal controls, the cytoplasm of anterior horn cells was diffusely HuR-positive. In short-duration and standard-duration ALS, the number of HuR-positive anterior horn cells was significantly decreased relative to the controls. DPCS and RIs were more frequent in short-duration ALS than in standard-duration ALS. The majority of DPCS areas and a small proportion of RIs, but not skeins, were positive for HuR. Immunoelectron microscopy showed that ribosome-like granular structures in DPCS areas and RIs were labeled with anti-HuR, whereas skeins were not. These findings suggest that colocalization of TDP-43 and SGs occurs at the early stage of TDP-43 aggregation.}, } @article {pmid37791873, year = {2023}, author = {Kour, S and Fortuna, T and Anderson, EN and Mawrie, D and Bilstein, J and Sivasubramanian, R and Ward, C and Roy, R and Rajasundaram, D and Sterneckert, J and Pandey, UB}, title = {Drosha-dependent microRNAs modulate FUS-mediated neurodegeneration in vivo.}, journal = {Nucleic acids research}, volume = {51}, number = {20}, pages = {11258-11276}, pmid = {37791873}, issn = {1362-4962}, support = {R01 NS081303/NS/NINDS NIH HHS/United States ; S10 OD028483/OD/NIH HHS/United States ; }, mesh = {Animals ; Amyotrophic Lateral Sclerosis/metabolism ; Drosophila/genetics/metabolism ; *MicroRNAs/genetics/metabolism ; Mutation ; Neurons/metabolism ; RNA-Binding Proteins/genetics/metabolism ; Neurodegenerative Diseases/metabolism ; *Heterogeneous-Nuclear Ribonucleoprotein Group F-H/metabolism ; Humans ; *Ribonuclease III/metabolism ; *Drosophila Proteins/metabolism ; }, abstract = {Mutations in the Fused in Sarcoma (FUS) gene cause the familial and progressive form of amyotrophic lateral sclerosis (ALS). FUS is a nuclear RNA-binding protein involved in RNA processing and the biogenesis of a specific set of microRNAs. Here we report that Drosha and two previously uncharacterized Drosha-dependent miRNAs are strong modulators of FUS expression and prevent the cytoplasmic segregation of insoluble mutant FUS in vivo. We demonstrate that depletion of Drosha mitigates FUS-mediated degeneration, survival and motor defects in Drosophila. Mutant FUS strongly interacts with Drosha and causes its cytoplasmic mis-localization into the insoluble FUS inclusions. Reduction in Drosha levels increases the solubility of mutant FUS. Interestingly, we found two Drosha dependent microRNAs, miR-378i and miR-6832-5p, which differentially regulate the expression, solubility and cytoplasmic aggregation of mutant FUS in iPSC neurons and mammalian cells. More importantly, we report different modes of action of these miRNAs against mutant FUS. Whereas miR-378i may regulate mutant FUS inclusions by preventing G3BP-mediated stress granule formation, miR-6832-5p may affect FUS expression via other proteins or pathways. Overall, our research reveals a possible association between ALS-linked FUS mutations and the Drosha-dependent miRNA regulatory circuit, as well as a useful perspective on potential ALS treatment via microRNAs.}, } @article {pmid37791834, year = {2024}, author = {Hyppa-Martin, J and Lilley, J and Chen, M and Friese, J and Schmidt, C and Bunnell, HT}, title = {A large-scale comparison of two voice synthesis techniques on intelligibility, naturalness, preferences, and attitudes toward voices banked by individuals with amyotrophic lateral sclerosis.}, journal = {Augmentative and alternative communication (Baltimore, Md. : 1985)}, volume = {40}, number = {1}, pages = {31-45}, doi = {10.1080/07434618.2023.2262032}, pmid = {37791834}, issn = {1477-3848}, mesh = {Adult ; Humans ; *Amyotrophic Lateral Sclerosis ; *Communication Devices for People with Disabilities ; *Communication Disorders/complications ; *Voice ; Dysarthria ; Speech Intelligibility ; }, abstract = {Amyotrophic lateral sclerosis (ALS) commonly results in the inability to produce natural speech, making speech-generating devices (SGDs) important. Historically, synthetic voices generated by SGDs were neither unique, nor age- or dialect-appropriate, which depersonalized SGD use. Voices generated by SGDs can now be customized via voice banking and should ideally sound uniquely like the individual's natural speech, be intelligible, and elicit positive reactions from communication partners. This large-scale 2 x 2 mixed between- and within-participants design examined perceptions of 831 adult listeners regarding custom synthetic voices created for two individuals diagnosed with ALS via two synthesis systems in common clinical use (waveform concatenation and statistical parametric synthesis). The study explored relationships among synthesis system, dysarthria severity, synthetic speech intelligibility, naturalness, and preferences, and also provided a preliminary examination of attitudes regarding the custom synthetic voices. Synthetic voices generated via statistical parametric synthesis trained on deep neural networks were more intelligible, natural, and preferred than voices produced via waveform concatenation, and were associated with more positive attitudes. The custom synthetic voice created from moderately dysarthric speech was more intelligible than the voice created from mildly dysarthric speech. Clinical implications and factors that may have contributed to the relative intelligibilities are discussed.}, } @article {pmid37791757, year = {2023}, author = {Rønne, ME and Tandrup, T and Madsen, M and Hunt, CJ and Myers, PN and Moll, JM and Holck, J and Brix, S and Strube, ML and Aachmann, FL and Wilkens, C and Svensson, B}, title = {Three alginate lyases provide a new gut Bacteroides ovatus isolate with the ability to grow on alginate.}, journal = {Applied and environmental microbiology}, volume = {89}, number = {10}, pages = {e0118523}, pmid = {37791757}, issn = {1098-5336}, mesh = {Polysaccharide-Lyases/metabolism ; Bacteroides ; Oligosaccharides/metabolism ; *Bacteria/metabolism ; *Alginates/metabolism ; Humans ; Substrate Specificity ; }, abstract = {Humans consume alginate in the form of seaweed, food hydrocolloids, and encapsulations, making the digestion of this mannuronic acid (M) and guluronic acid (G) polymer of key interest for human health. To increase knowledge on alginate degradation in the gut, a gene catalog from human feces was mined for potential alginate lyases (ALs). The predicted ALs were present in nine species of the Bacteroidetes phylum, of which two required supplementation of an endo-acting AL, expected to mimic cross-feeding in the gut. However, only a new isolate grew on alginate. Whole-genome sequencing of this alginate-utilizing isolate suggested that it is a new Bacteroides ovatus strain harboring a polysaccharide utilization locus (PUL) containing three ALs of families: PL6, PL17, and PL38. The BoPL6 degraded polyG to oligosaccharides of DP 1-3, and BoPL17 released 4,5-unsaturated monouronate from polyM. BoPL38 degraded both alginates, polyM, polyG, and polyMG, in endo-mode; hence, it was assumed to deliver oligosaccharide substrates for BoPL6 and BoPL17, corresponding well with synergistic action on alginate. BoPL17 and BoPL38 crystal structures, determined at 1.61 and 2.11 Å, respectively, showed (α/α)6-barrel + anti-parallel β-sheet and (α/α)7-barrel folds, distinctive for these PL families. BoPL17 had a more open active site than the two homologous structures. BoPL38 was very similar to the structure of an uncharacterized PL38, albeit with a different triad of residues possibly interacting with substrate in the presumed active site tunnel. Altogether, the study provides unique functional and structural insights into alginate-degrading lyases of a PUL in a human gut bacterium.IMPORTANCEHuman ingestion of sustainable biopolymers calls for insight into their utilization in our gut. Seaweed is one such resource with alginate, a major cell wall component, used as a food hydrocolloid and for encapsulation of pharmaceuticals and probiotics. Knowledge is sparse on the molecular basis for alginate utilization in the gut. We identified a new Bacteroides ovatus strain from human feces that grew on alginate and encoded three alginate lyases in a gene cluster. BoPL6 and BoPL17 show complementary specificity toward guluronate (G) and mannuronate (M) residues, releasing unsaturated oligosaccharides and monouronic acids. BoPL38 produces oligosaccharides degraded by BoPL6 and BoPL17 from both alginates, G-, M-, and MG-substrates. Enzymatic and structural characterization discloses the mode of action and synergistic degradation of alginate by these alginate lyases. Other bacteria were cross-feeding on alginate oligosaccharides produced by an endo-acting alginate lyase. Hence, there is an interdependent community in our guts that can utilize alginate.}, } @article {pmid37791472, year = {2023}, author = {Zhang, Y and Nelson, SCK and Viera Ortiz, AP and Lee, EB and Fairman, R}, title = {C9orf72 proline-arginine dipeptide repeats disrupt the proteasome and perturb proteolytic activities.}, journal = {Journal of neuropathology and experimental neurology}, volume = {82}, number = {11}, pages = {901-910}, pmid = {37791472}, issn = {1554-6578}, support = {P40 OD018537/OD/NIH HHS/United States ; P01 AG066597/AG/NIA NIH HHS/United States ; R01 NS095793/NS/NINDS NIH HHS/United States ; P30AG072979/NH/NIH HHS/United States ; P30 AG072979/AG/NIA NIH HHS/United States ; }, mesh = {Animals ; Humans ; *Amyotrophic Lateral Sclerosis/pathology ; Drosophila melanogaster/genetics/metabolism ; Proteasome Endopeptidase Complex/genetics/metabolism ; C9orf72 Protein/genetics/metabolism ; Arginine/genetics/metabolism ; Proteolysis ; Dipeptides/genetics/metabolism ; Proline/genetics/metabolism ; *Frontotemporal Dementia/genetics ; DNA Repeat Expansion ; }, abstract = {The hexanucleotide G4C2 repeat expansion in C9orf72 is the most frequent genetic cause of familial amyotrophic lateral sclerosis (ALS). Aberrant translation of this hexanucleotide sequence leads to production of 5 dipeptide repeats (DPRs). One of these DPRs is proline-arginine (polyPR), which is found in C9orf72-expanded ALS (C9ALS) patient brain tissue and is neurotoxic across multiple model systems. PolyPR was previously reported to bind and impair proteasomes in vitro. Nevertheless, the clinical relevance of the polyPR-proteasome interaction and its functional consequences in vivo are yet to be established. Here, we aim to confirm and functionally characterize polyPR-induced impairment of proteolysis in C9ALS patient tissue and an in vivo model system. Confocal microscopy and immunofluorescence studies on both human and Drosophila melanogaster brain tissues revealed sequestration of proteasomes by polyPR into inclusion-like bodies. Co-immunoprecipitation in D. melanogaster showed that polyPR strongly binds to the proteasome. In vivo, functional evidence for proteasome impairment is further shown by the accumulation of ubiquitinated proteins along with lysosomal accumulation and hyper-acidification, which can be rescued by a small-molecule proteasomal enhancer. Together, we provide the first clinical report of polyPR-proteasome interactions and offer in vivo evidence proposing polyPR-induced proteolytic dysfunction as a pathogenic mechanism in C9ALS.}, } @article {pmid37791043, year = {2023}, author = {Richter, V and Neumann, M and Green, JR and Richburg, B and Roesler, O and Kothare, H and Ramanarayanan, V}, title = {Remote Assessment for ALS using Multimodal Dialog Agents: Data Quality, Feasibility and Task Compliance.}, journal = {Interspeech}, volume = {2023}, number = {}, pages = {5441-5445}, pmid = {37791043}, issn = {2308-457X}, support = {K24 DC016312/DC/NIDCD NIH HHS/United States ; R42 DC019877/DC/NIDCD NIH HHS/United States ; }, abstract = {We investigate the feasibility, task compliance and audiovisual data quality of a multimodal dialog-based solution for remote assessment of Amyotrophic Lateral Sclerosis (ALS). 53 people with ALS and 52 healthy controls interacted with Tina, a cloud-based conversational agent, in performing speech tasks designed to probe various aspects of motor speech function while their audio and video was recorded. We rated a total of 250 recordings for audio/video quality and participant task compliance, along with the relative frequency of different issues observed. We observed excellent compliance (98%) and audio (95.2%) and visual quality rates (84.8%), resulting in an overall yield of 80.8% recordings that were both compliant and of high quality. Furthermore, recording quality and compliance were not affected by level of speech severity and did not differ significantly across end devices. These findings support the utility of dialog systems for remote monitoring of speech in ALS.}, } @article {pmid37790622, year = {2023}, author = {Renz, M and Müller, L and Herbst, M and Riedel, J and Mohnke, K and Ziebart, A and Ruemmler, R}, title = {Analysis of cerebral Interleukin-6 and tumor necrosis factor alpha patterns following different ventilation strategies during cardiac arrest in pigs.}, journal = {PeerJ}, volume = {11}, number = {}, pages = {e16062}, pmid = {37790622}, issn = {2167-8359}, mesh = {Animals ; *Cardiopulmonary Resuscitation/methods ; Cytokines ; *Heart Arrest/therapy ; Interleukin-6/genetics ; Prospective Studies ; RNA, Messenger ; Swine ; Tumor Necrosis Factor-alpha/genetics ; }, abstract = {Hypoxia-induced neuroinflammation after cardiac arrest has been shown to be mitigated by different ventilation methods. In this prospective randomized animal trial, 35 landrace pigs were randomly divided into four groups: intermittent positive pressure ventilation (IPPV), synchronized ventilation 20 mbar (SV 20 mbar), chest compression synchronized ventilation 40 mbar (CCSV 40 mbar) and a control group (Sham). After inducing ventricular fibrillation, basic life support (BLS) and advanced life support (ALS) were performed, followed by post-resuscitation monitoring. After 6 hours, the animals were euthanized, and direct postmortem brain tissue samples were taken from the hippocampus (HC) and cortex (Cor) for molecular biological investigation of cytokine mRNA levels of Interleukin-6 (IL-6) and tumor necrosis factor alpha (TNFα). The data analysis showed that CCSV 40 mbar displayed low TNFα mRNA-levels, especially in the HC, while the highest TNFα mRNA-levels were detected in SV 20 mbar. The results indicate that chest compression synchronized ventilation may have a potential positive impact on the cytokine expression levels post-resuscitation. Further studies are needed to derive potential therapeutic algorithms from these findings.}, } @article {pmid37789566, year = {2024}, author = {Raymond, J and Berry, J and Kasarskis, EJ and Larson, T and Horton, DK and Mehta, P}, title = {A brief report on juvenile amyotrophic lateral sclerosis cases in the United States National ALS Registry: 2010-2018.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {25}, number = {1-2}, pages = {211-213}, pmid = {37789566}, issn = {2167-9223}, support = {CC999999/ImCDC/Intramural CDC HHS/United States ; }, mesh = {Adult ; Humans ; Male ; United States/epidemiology ; Young Adult ; *Amyotrophic Lateral Sclerosis/diagnosis/epidemiology ; Risk Factors ; Registries ; Databases, Factual ; }, abstract = {Juvenile ALS (jALS) is a rare form of ALS, defined as symptom onset before age 25. This report describes the demographic characteristics of confirmed and likely jALS cases in a large cohort of ALS patients ascertained in the National ALS Registry (Registry) from 2010 to 2018. Patients in the Registry must be at least 18 years of age. Of the 44 identified patients, 37.8% were diagnosed at age 24, were more likely to be nonwhite (54.5%), male (79.5%), and live in the Midwest or Northeast regions (54.5%) of the US. Some 68.9% of the jALS cases were received from federal administrative databases, and 16% came from the web portal only. Demographic characteristics for jALS cases in the Registry differed from previous publications examining ALS cases for all adults. More research is needed to better understand risk factors contributing to jALS, which could lead to earlier diagnosis and therapeutic interventions.}, } @article {pmid37789557, year = {2024}, author = {Kläppe, U and Sennfält, S and Lovik, A and Finn, A and Bofaisal, U and Zetterberg, H and Blennow, K and Piehl, F and Kmezic, I and Press, R and Samuelsson, K and Månberg, A and Fang, F and Ingre, C}, title = {Neurodegenerative biomarkers outperform neuroinflammatory biomarkers in amyotrophic lateral sclerosis.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {25}, number = {1-2}, pages = {150-161}, doi = {10.1080/21678421.2023.2263874}, pmid = {37789557}, issn = {2167-9223}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis ; Neuroinflammatory Diseases ; Case-Control Studies ; Biomarkers ; Prognosis ; Neurofilament Proteins/cerebrospinal fluid ; }, abstract = {OBJECTIVE: To describe the diagnostic and prognostic performance, and longitudinal trajectories, of potential biomarkers of neuroaxonal degeneration and neuroinflammation in amyotrophic lateral sclerosis (ALS).

METHODS: This case-control study included 192 incident ALS patients, 42 ALS mimics, 114 neurological controls, and 117 healthy controls from Stockholm, Sweden. Forty-four ALS patients provided repeated measurements. We assessed biomarkers of (1)neuroaxonal degeneration: neurofilament light (NfL) and phosphorylated neurofilament heavy (pNfH) in cerebrospinal fluid (CSF) and NfL in serum, and (2)neuroinflammation: chitotriosidase-1 (CHIT1) and monocyte chemoattractant protein 1 (MCP-1) in CSF. To evaluate diagnostic performance, we calculated the area under the curve (AUC). To estimate prognostic performance, we applied quantile regression and Cox regression. We used linear regression models with robust standard errors to assess temporal changes over time.

RESULTS: Neurofilaments performed better at differentiating ALS patients from mimics (AUC: pNfH 0.92, CSF NfL 0.86, serum NfL 0.91) than neuroinflammatory biomarkers (AUC: CHIT1 0.71, MCP-1 0.56). Combining biomarkers did not improve diagnostic performance. Similarly, neurofilaments performed better than neuroinflammatory biomarkers at predicting functional decline and survival. The stratified analysis revealed differences according to the site of onset: in bulbar patients, neurofilaments and CHIT1 performed worse at predicting survival and correlations were lower between biomarkers. Finally, in bulbar patients, neurofilaments and CHIT1 increased longitudinally but were stable in spinal patients.

CONCLUSIONS: Biomarkers of neuroaxonal degeneration displayed better diagnostic and prognostic value compared with neuroinflammatory biomarkers. However, in contrast to spinal patients, in bulbar patients neurofilaments and CHIT1 performed worse at predicting survival and seemed to increase over time.}, } @article {pmid37787835, year = {2024}, author = {Li, S and Zhao, L and Xiao, J and Guo, Y and Fu, R and Zhang, Y and Xu, S}, title = {The gut microbiome: an important role in neurodegenerative diseases and their therapeutic advances.}, journal = {Molecular and cellular biochemistry}, volume = {479}, number = {9}, pages = {2217-2243}, pmid = {37787835}, issn = {1573-4919}, support = {No. 81973626, No. 81774059//National Natural Science Foundation of China/ ; No. 21JCYBJC01620//Tianjin Municipal Science and Technology Commission of China/ ; No. 2021099//Tianjin Health Committee/ ; No. 2021KJ146//Tianjin Education Committee/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; *Neurodegenerative Diseases/therapy/microbiology ; *Fecal Microbiota Transplantation ; *Probiotics/therapeutic use ; Animals ; Parkinson Disease/therapy/microbiology ; Alzheimer Disease/therapy/microbiology ; }, abstract = {There are complex interactions between the gut and the brain. With increasing research on the relationship between gut microbiota and brain function, accumulated clinical and preclinical evidence suggests that gut microbiota is intimately involved in the pathogenesis of neurodegenerative diseases (NDs). Increasingly studies are beginning to focus on the association between gut microbiota and central nervous system (CNS) degenerative pathologies to find potential therapies for these refractory diseases. In this review, we summarize the changes in the gut microbiota in Alzheimer's disease, Parkinson's disease, multiple sclerosis, and amyotrophic lateral sclerosis and contribute to our understanding of the function of the gut microbiota in NDs and its possible involvement in the pathogenesis. We subsequently discuss therapeutic approaches targeting gut microbial abnormalities in these diseases, including antibiotics, diet, probiotics, and fecal microbiota transplantation (FMT). Furthermore, we summarize some completed and ongoing clinical trials of interventions with gut microbes for NDs, which may provide new ideas for studying NDs.}, } @article {pmid37787812, year = {2024}, author = {Beswick, E and Johnson, M and Newton, J and Dakin, R and Stenson, A and Abrahams, S and Carson, A and Chandran, S and Pal, S}, title = {Factors impacting trial participation in people with motor neuron disease.}, journal = {Journal of neurology}, volume = {271}, number = {1}, pages = {543-552}, pmid = {37787812}, issn = {1432-1459}, mesh = {Female ; Humans ; Male ; *Amyotrophic Lateral Sclerosis/therapy ; *Motor Neuron Disease/therapy ; Probability ; Prospective Studies ; Randomized Controlled Trials as Topic ; Adaptive Clinical Trials as Topic ; }, abstract = {Motor neuron disease (MND) is a rapidly progressive neurodegenerative disorder with limited treatment options. Historically, neurological trials have been plagued by suboptimal recruitment and high rates of attrition. The Motor Neuron Disease-Systematic Multi-Arm Randomised Adaptive Trial (MND-SMART) seeks to identify effective disease modifying drugs. This study investigates person-specific factors affecting recruitment and retention. Improved understanding of these factors may improve trial protocol design, optimise recruitment and retention. Participants with MND completed questionnaires and this was supplemented with clinical data. 12 months after completing the questionnaires we used MND-SMART recruitment data to establish if members of our cohort engaged with the trial. 120 people with MND completed questionnaires for this study. Mean age at participation was 66 (SD = 9), 14% (n = 17) were categorised as long survivors, with 68% (n = 81) of participants male and 60% (n = 73) had the ALS sub-type. Of the 120 study participants, 50% (n = 60) were randomised into MND-SMART and 78% (n = 94) expressed interest an in participating. After the 1-year follow-up period 65% (n = 39) of the 60 randomised participants remained in MND-SMART. Older age was significantly associated with reduced likelihood of participation (OR = 0.92, 95% CI = 0.88-0.96, p = 0.000488). The findings show that people with MND are highly motivated to engage in research, but older individuals remain significantly less likely to participate. We recommend the inclusion of studies to explore characteristics of prospective and current participants alongside trials.}, } @article {pmid37787459, year = {2023}, author = {Wei, S and Yang, Y and Wang, Y}, title = {Proximity Proteomics Revealed Aberrant mRNA Splicing Elicited by ALS-Linked Profilin-1 Mutants.}, journal = {Analytical chemistry}, volume = {95}, number = {41}, pages = {15141-15145}, pmid = {37787459}, issn = {1520-6882}, support = {R35 ES031707/ES/NIEHS NIH HHS/United States ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/pathology ; Profilins/genetics/metabolism ; Actins/metabolism ; Proteomics ; Mutation ; Basic Helix-Loop-Helix Transcription Factors/genetics ; }, abstract = {Profilin 1 (PFN1) is a cytoskeleton protein that modulates actin dynamics through binding to monomeric actin and polyproline-containing proteins. Mutations in PFN1 have been linked to the pathogenesis of familial amyotrophic lateral sclerosis (ALS). Here, we employed an unbiased proximity labeling strategy in combination with proteomic analysis for proteome-wide profiling of proteins that differentially interact with mutant and wild-type (WT) PFN1 proteins in human cells. We uncovered 11 mRNA splicing proteins that are preferentially enriched in the proximity proteomes of the two ALS-linked PFN1 variants, C71G and M114T, over that of wild-type PFN1. We validated the preferential interactions of the ALS-linked PFN1 variants with two mRNA splicing factors, hnRNPC and U2AF2, by immunoprecipitation, followed with immunoblotting. We also found that the two ALS-linked PFN1 variants promoted the exonization of Alu elements in the mRNAs of MTO1, TCFL5, WRN and POLE genes in human cells. Together, we showed that the two ALS-linked PFN1 variants interacted preferentially with mRNA splicing proteins, which elicited aberrant exonization of the Alu elements in mRNAs. Thus, our work provided pivotal insights into the perturbations of ALS-linked PFN1 variants in RNA biology and their potential contributions to ALS pathology.}, } @article {pmid37786726, year = {2023}, author = {Bell, AM and Utting, C and Dickie, AC and Kucharczyk, MW and Quillet, R and Gutierrez-Mecinas, M and Razlan, ANB and Cooper, AH and Lan, Y and Hachisuka, J and Weir, GA and Bannister, K and Watanabe, M and Kania, A and Hoon, MA and Macaulay, IC and Denk, F and Todd, AJ}, title = {Deep sequencing of Phox2a nuclei reveals five classes of anterolateral system neurons.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {37786726}, issn = {2692-8205}, support = {MR/T01072X/1/MRC_/Medical Research Council/United Kingdom ; MRF-160-0015-ELP-DENK-C0844/MRF_/MRF_/United Kingdom ; MR/W004739/1/MRC_/Medical Research Council/United Kingdom ; MR/V033638/1/MRC_/Medical Research Council/United Kingdom ; 26815/CRUK_/Cancer Research UK/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; }, abstract = {The anterolateral system (ALS) is a major ascending pathway from the spinal cord that projects to multiple brain areas and underlies the perception of pain, itch and skin temperature. Despite its importance, our understanding of this system has been hampered by the considerable functional and molecular diversity of its constituent cells. Here we use fluorescence-activated cell sorting to isolate ALS neurons belonging to the Phox2a-lineage for single-nucleus RNA sequencing. We reveal five distinct clusters of ALS neurons (ALS1-5) and document their laminar distribution in the spinal cord using in situ hybridization. We identify 3 clusters of neurons located predominantly in laminae I-III of the dorsal horn (ALS1-3) and two clusters with cell bodies located in deeper laminae (ALS4 & ALS5). Our findings reveal the transcriptional logic that underlies ALS neuronal diversity in the adult mouse and uncover the molecular identity of two previously identified classes of projection neurons. We also show that these molecular signatures can be used to target groups of ALS neurons using retrograde viral tracing. Overall, our findings provide a valuable resource for studying somatosensory biology and targeting subclasses of ALS neurons.}, } @article {pmid37783557, year = {2023}, author = {Chen, D and Huang, H and Saberi, H and Sharma, HS}, title = {Positive and negative cell therapy in randomized control trials for central nervous system diseases.}, journal = {International review of neurobiology}, volume = {171}, number = {}, pages = {241-254}, doi = {10.1016/bs.irn.2023.05.017}, pmid = {37783557}, issn = {2162-5514}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy ; Quality of Life ; *Central Nervous System Diseases/therapy ; Cell- and Tissue-Based Therapy ; *Parkinson Disease/therapy ; Brain Damage, Chronic ; }, abstract = {Neurorestorative cell therapies have been tested to treat patients with nervous system diseases for over 20 years. Now it is still hard to answer which kinds of cells can really play a role on improving these patients' quality of life. Non-randomized clinical trials or studies could not provide strong evidences in answering this critical question. In this review, we summarized randomized clinical trials of cell therapies for central nervous diseases, such as stroke, spinal cord injury, cerebral palsy (CP), Parkinson's disease (PD), multiple sclerosis (MS), brain trauma, amyotrophic lateral sclerosis (ALS), etc. Most kinds of cell therapies demonstrated negative results for stoke, brain trauma and amyotrophic lateral sclerosis. A few kinds of cell therapies showed neurorestorative effects in this level of evidence-based medicine, such as olfactory ensheating cells for chronic ischemic stroke. Some kinds of cells showed positive or negative effects from different teams in the same or different diseases. We analyzed the possible failed reasons of negative results and the cellular bio-propriety basis of positive results. Based on therapeutic results of randomized control trials and reasonable analysis, we recommend: (1) to further conduct trials for successful cell therapies with positive results to increase neurorestorative effects; (2) to avoid in repeating failed cell therapies with negative results in same diseases because it is nonsense for them to be done with similar treatment methods, such as cell dosage, transplanting way, time of window, etc. Furthermore, we strongly suggest not to do non-randomized clinical trials for cells that had shown negative results in randomized clinical trials.}, } @article {pmid37782813, year = {2023}, author = {Pennisi, F and Lo Presti, T and Ricciardi, GE and Dalla Valle, Z and Minerva, M and Privitera, G and Signorelli, C}, title = {Training and career opportunities for residencies in Hygiene and Preventive Medicine: results of a survey on 39 Italian schools.}, journal = {Igiene e sanita pubblica}, volume = {80}, number = {4}, pages = {94-100}, pmid = {37782813}, issn = {0019-1639}, mesh = {Humans ; *Internship and Residency ; State Medicine ; Public Health/education ; Hygiene/education ; Universities ; Preventive Medicine/education ; }, abstract = {INTRODUCTION: The Italian National Health Service (SSN) is currently grappling. with a complex situation, characterized by a persistent shortage of medical personnel and the divergent aspirations of young medical graduates. Additionally, recent regulatory developments concerning specialist training further contribute to the intricacies of the landscape, calling for a comprehensive analysis of the challenges and opportunities within the sector. This study aims to provide an updated overview of the current placement of medical graduates, residents and specialists in the specific hygiene and preventive medicine (Public Health) field.

METHODS: Data on admissions, withdrawals and resignations were obtained from the Ministries of Universities and Health and from the archives of the "Associazione Liberi Specializzandi" (ALS). Information regarding the professional prospects for specialists and residents in the field of Public Health was gathered through a tailored survey conducted by the "Consulta dei Medici in Formazione Specialistica" (Council of Medical Residents) of the Italian Society of Hygiene (SItI).

RESULTS: In 2022, a total of 483 specialization contracts were granted, indicating a decrease of 37% compared to the previous year. Notably, 85 positions (17.6%) remained unallocated or resulted in dropouts. Six months after completing their residency, 1.5% of hygiene residents were still actively seeking employment. On a positive note, 75.4% of fourth-year residents secured contracts under the "Decreto Calabria". Career opportunities within the Italian SSN have witnessed growth, with a significant proportion of placements in territorial services and hospital medical directorates.

DISCUSSION AND CONCLUSIONS: The updating of training programs provided by residency schools and the exploration of innovative approaches are of paramount importance to address the urgent need for high-quality training and to cater to the requirements of the national health system.}, } @article {pmid37782796, year = {2023}, author = {Huang, J and Fan, X and Jin, X and Teng, L and Yan, N}, title = {Dual-pocket inhibition of Nav channels by the antiepileptic drug lamotrigine.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {120}, number = {41}, pages = {e2309773120}, pmid = {37782796}, issn = {1091-6490}, mesh = {Humans ; Anticonvulsants/pharmacology ; Lamotrigine/pharmacology ; *Cannabidiol ; Sodium/metabolism ; *Voltage-Gated Sodium Channels/chemistry ; }, abstract = {Voltage-gated sodium (Nav) channels govern membrane excitability, thus setting the foundation for various physiological and neuronal processes. Nav channels serve as the primary targets for several classes of widely used and investigational drugs, including local anesthetics, antiepileptic drugs, antiarrhythmics, and analgesics. In this study, we present cryogenic electron microscopy (cryo-EM) structures of human Nav1.7 bound to two clinical drugs, riluzole (RLZ) and lamotrigine (LTG), at resolutions of 2.9 Å and 2.7 Å, respectively. A 3D EM reconstruction of ligand-free Nav1.7 was also obtained at 2.1 Å resolution. RLZ resides in the central cavity of the pore domain and is coordinated by residues from repeats III and IV. Whereas one LTG molecule also binds to the central cavity, the other is found beneath the intracellular gate, known as site BIG. Therefore, LTG, similar to lacosamide and cannabidiol, blocks Nav channels via a dual-pocket mechanism. These structures, complemented with docking and mutational analyses, also explain the structure-activity relationships of the LTG-related linear 6,6 series that have been developed for improved efficacy and subtype specificity on different Nav channels. Our findings reveal the molecular basis for these drugs' mechanism of action and will aid the development of novel antiepileptic and pain-relieving drugs.}, } @article {pmid37782409, year = {2023}, author = {Lee, SY and Cho, HY and Oh, JP and Park, J and Bae, SH and Park, H and Kim, EJ and Lee, JH}, title = {Therapeutic Effects of Combination of Nebivolol and Donepezil: Targeting Multifactorial Mechanisms in ALS.}, journal = {Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics}, volume = {20}, number = {6}, pages = {1779-1795}, pmid = {37782409}, issn = {1878-7479}, support = {S3030175//Korea Technology and Information Promotion Agency for SMEs/ ; }, mesh = {Humans ; Mice ; Animals ; *Amyotrophic Lateral Sclerosis/drug therapy/genetics/metabolism ; Donepezil/therapeutic use ; Nebivolol/therapeutic use/metabolism ; Phosphatidylinositol 3-Kinases/metabolism ; HeLa Cells ; Quality of Life ; Spinal Cord/metabolism ; Disease Progression ; Disease Models, Animal ; Mice, Transgenic ; Superoxide Dismutase/genetics ; Superoxide Dismutase-1/genetics ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by progressive loss of motor neurons in the spinal cord. Although the disease's pathophysiological mechanism remains poorly understood, multifactorial mechanisms affecting motor neuron loss converge to worsen the disease. Although two FDA-approved drugs, riluzole and edaravone, targeting excitotoxicity and oxidative stress, respectively, are available, their efficacies are limited to extending survival by only a few months. Here, we developed combinatorial drugs targeting multifactorial mechanisms underlying key components in ALS disease progression. Using data analysis based on the genetic information of patients with ALS-derived cells and pharmacogenomic data of the drugs, a combination of nebivolol and donepezil (nebivolol-donepezil) was identified for ALS therapy. Here, nebivolol-donepezil markedly reduced the levels of cytokines in the microglial cell line, inhibited nuclear factor-κB (NF-κB) nucleus translocation in the HeLa cell and substantially protected against excitotoxicity-induced neuronal loss by regulating the PI3K-Akt pathway. Nebivolol-donepezil significantly promoted the differentiation of neural progenitor cells (NPC) into motor neurons. Furthermore, we verified the low dose efficacy of nebivolol-donepezil on multiple indices corresponding to the quality of life of patients with ALS in vivo using SOD1[G93A] mice. Nebivolol-donepezil delayed motor function deterioration and halted motor neuronal loss in the spinal cord. Drug administration effectively suppressed muscle atrophy by mitigating the proportion of smaller myofibers and substantially reducing phospho-neurofilament heavy chain (pNF-H) levels in the serum, a promising ALS biomarker. High-dose nebivolol-donepezil significantly prolonged survival and delayed disease onset compared with vehicle-treated mice. These results indicate that the combination of nebivolol-donepezil efficiently prevents ALS disease progression, benefiting the patients' quality of life and life expectancy.}, } @article {pmid37782260, year = {2023}, author = {Bchara, L and Eritja, R and Gargallo, R and Benavente, F}, title = {Rapid and Highly Efficient Separation of i-Motif DNA Species by CE-UV and Multivariate Curve Resolution.}, journal = {Analytical chemistry}, volume = {95}, number = {41}, pages = {15189-15198}, pmid = {37782260}, issn = {1520-6882}, mesh = {*DNA ; Spectrophotometry ; Spectrophotometry, Ultraviolet/methods ; Temperature ; *Electrophoresis, Capillary/methods ; }, abstract = {The i-motif is a class of nonstandard DNA structure with potential biological implications. A novel capillary electrophoresis with an ultraviolet absorption spectrophotometric detection (CE-UV) method has been developed for the rapid analysis of the i-motif folding equilibrium as a function of pH and temperature. The electrophoretic analyses are performed in reverse polarity of the separation voltage with 32 cm long fused silica capillaries permanently coated with hydroxypropyl cellulose (HPC), after an appropriate conditioning procedure was used to achieve good repeatability. However, the electrophoretic separation between the folded and unfolded conformers of the studied cytosine-rich i-motif sequences (i.e., TT, Py39WT, and nmy01) is compromised, especially for Py39WT and nmy01, which result in completely overlapped peaks. Therefore, deconvolution with multivariate curve resolution-alternating least-squares (MCR-ALS) has been required for the efficient separation of the folded and unfolded species found at different concentration levels at pH 6.5 and between 12 and 40 °C, taking advantage of the small dissimilarities in the electrophoretic mobilities and UV spectra levels. MCR-ALS has also provided quantitative information that has been used to estimate melting temperatures (Tm), which are similar to those determined by UV and circular dichroism (CD) spectroscopies. The obtained results demonstrate that CE-UV assisted by MCR-ALS may become a very useful tool to get novel insight into the folding of i-motifs and other complex DNA structures.}, } @article {pmid37782142, year = {2023}, author = {Rahman, A and Saikia, B and Baruah, A}, title = {In silico analysis of SOD1 aggregation inhibition modes of tertiary amine pyrazolone and pyrano coumarin ferulate as ALS drug candidates.}, journal = {Physical chemistry chemical physics : PCCP}, volume = {25}, number = {39}, pages = {26833-26846}, doi = {10.1039/d3cp03978a}, pmid = {37782142}, issn = {1463-9084}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics ; Molecular Docking Simulation ; Molecular Dynamics Simulation ; Mutation ; *Neurodegenerative Diseases ; Protein Folding ; Superoxide Dismutase-1/chemistry/genetics ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease, the familial form (fALS) of which is often cognate to mutations in the antioxidant enzyme Cu/Zn superoxide dismutase 1 (SOD1) leading to misfolding and aggregation. Two small molecules, a tertiary amine pyrazolone (TAP) and a pyrano coumarin ferulate (PCF) were suggested to be ALS drug candidates following experimental observation of their ability to inhibit SOD1 protein misfolding and aggregation. The present work aims at computational investigation of these experimentally proposed drug candidates to gain insight into their mechanism of SOD1 misfolding and aggregation inhibition. On the basis of molecular docking, molecular dynamics simulation, MM-PBSA and per-residue energy decomposition analysis, we examined the specific interactions of TAP and PCF with three probable binding sites of SOD1, namely, dimeric interface cavity, W32 and, UMP binding sites. Results suggest that the binding of TAP at W32 and at UMP sites are least probable due to absence of any favorable interaction. The binding of TAP to dimeric cavity is also unstable due to strong unfavorable interactions. In case of PCF, binding at the UMP site is least probable while binding at dimeric cavity is accompanied by unfavorable interactions. PCF, however, exhibits stable binding with the W32 binding site of SOD1 by stabilizing the solvent accessible hydrophobic residues, which otherwise would have acted as contact points for aggregation. Thus the results imply that compound PCF functions as an inhibitior of SOD1 misfolding/aggregation through direct interaction with the protein SOD1 at the W32 binding site. However, TAP is likely to act as an inhibitor through a different mechanism rather than direct interaction with the protein SOD1. These results apart from reinforcing previous experimental findings, shed light on the probable mechanism of action of the proposed drug candidates.}, } @article {pmid37781884, year = {2023}, author = {Erdag, E and Haskologlu, IC and Mercan, M and Abacioglu, N and Sehirli, AO}, title = {An in silico investigation: Can melatonin serve as an adjuvant in NR1D1-linked chronotherapy for amyotrophic lateral sclerosis?.}, journal = {Chronobiology international}, volume = {40}, number = {10}, pages = {1395-1403}, doi = {10.1080/07420528.2023.2265476}, pmid = {37781884}, issn = {1525-6073}, mesh = {Animals ; Humans ; *Melatonin/pharmacology ; Circadian Rhythm/physiology ; *Amyotrophic Lateral Sclerosis/drug therapy ; Molecular Docking Simulation ; Chronotherapy/methods ; Nuclear Receptor Subfamily 1, Group D, Member 1/genetics ; }, abstract = {Chronobiology, which studies biological rhythms and their impacts on health, presents a potential avenue for treating amyotrophic lateral sclerosis. Clock gene-related therapies, focusing on genes responsible for regulating biological rhythms, may hold promise in the treatment. Among these clock genes, nuclear receptor subfamily 1 Group D member 1 (NR1D1) plays a vital role in neurodegenerative diseases. In this particular study, it was aimed to investigate the potential of FDA-approved drugs commonly used in amyotrophic lateral sclerosis treatment and melatonin, a hormone known for its role in regulating sleep-wake cycles, as ligands for clock gene-related therapy. The ligands were subjected to molecular docking and molecular dynamics simulation methods against the NR1D1 clock gene. These results suggested that combining melatonin with FDA-approved medications commonly used in the treatment might yield positive outcomes. This study provides preliminary data and lays the groundwork for future investigations involving in vitro (laboratory-based) and in vivo (animal or human-based) research on chronotherapy. In summary, this research highlights the potential of clock gene-related therapy utilizing melatonin in conjunction with FDA-approved drugs for amyotrophic lateral sclerosis treatment, offering insights into novel treatment strategies. The findings underscore the need for further studies to explore the effectiveness of this hypothetical approach in experimental and clinical settings.}, } @article {pmid37781096, year = {2023}, author = {Yu, H and Xiong, M and Zhang, Z}, title = {The role of glycogen synthase kinase 3 beta in neurodegenerative diseases.}, journal = {Frontiers in molecular neuroscience}, volume = {16}, number = {}, pages = {1209703}, pmid = {37781096}, issn = {1662-5099}, abstract = {Neurodegenerative diseases (NDDs) pose an increasingly prevalent threat to the well-being and survival of elderly individuals worldwide. NDDs include Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), and so on. They are characterized by progressive loss or dysfunction of neurons in the central or peripheral nervous system and share several cellular and molecular mechanisms, including protein aggregation, mitochondrial dysfunction, gene mutations, and chronic neuroinflammation. Glycogen synthase kinase-3 beta (GSK-3β) is a serine/threonine kinase that is believed to play a pivotal role in the pathogenesis of NDDs. Here we summarize the structure and physiological functions of GSK3β and explore its involvement in NDDs. We also discussed its potential as a therapeutic target.}, } @article {pmid37780700, year = {2023}, author = {Li, H and Xuan, T and Xu, T and Yang, J and Cheng, J and Wang, Z}, title = {SIGMAR1 variants in ALS-PD complex cases: a case report of a novel mutation and literature review.}, journal = {Frontiers in neurology}, volume = {14}, number = {}, pages = {1242472}, pmid = {37780700}, issn = {1664-2295}, abstract = {Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by progressive degeneration of upper and lower motor neurons, with occasional involvement of the extrapyramidal system. Mutations in the sigma non-opioid intracellular receptor 1 (SIGMAR1) gene have been identified as one of the causes of ALS. Here, we present a case of a 49-year-old man diagnosed with ALS-Parkinson's disease (PD) complex. The patient exhibited bradykinesia and tremor, and whole-exome sequencing revealed homozygous mutations in the SIGMAR1 gene (c.446-2A > T). In addition, we conducted an investigation into the clinical and molecular phenotype of previously reported variants of SIGMAR1 associated with ALS. This case report aims to raise awareness among physicians regarding atypical phenotypes of amyotrophic lateral sclerosis and to encourage further research on the factors leading to SIGMAR1 mutations in patients.}, } @article {pmid37780560, year = {2023}, author = {Zwicker, J and Smith, IC and Rice, J and Murphy, R and Breiner, A and McNeely, S and Duff, M and Buenger, U and Zehrt, B and Nogo, D and Watt, CL}, title = {Palliative care at any stage of amyotrophic lateral sclerosis: a prospective feasibility study.}, journal = {Frontiers in medicine}, volume = {10}, number = {}, pages = {1204816}, pmid = {37780560}, issn = {2296-858X}, abstract = {INTRODUCTION: Many patients with amyotrophic lateral sclerosis (ALS) receive palliative care (PC) very late or not at all. The impact of PC on patients with ALS and caregivers has not been quantified. Study goals included (1) measuring the impact of early PC on quality of life and mood of patients/caregivers and (2) describing patient/caregiver satisfaction with PC.

METHODS: The study was a non-randomized, prospective feasibility study of patients with ALS being treated at The Ottawa Hospital ALS Clinic and their caregivers. Exclusion criteria were age < 18 years, inability to complete questionnaires, and prior receipt of PC. The ALS Specific Quality of Life-Revised (ALSSQOL-R) questionnaire (patients only) and Hospital Anxiety and Depression Scale (HADS) were completed at regular intervals for up to 2 years. Patients accepting a PC consultation completed a post-PC satisfaction survey. Primary outcome measures included ALSSQOL-R and HADS scores compared before and after PC consultation, and between groups receiving and not receiving a PC consultation. Secondary outcome measures included responses on the post-PC satisfaction survey (1 = strongly disagree, 5 = strongly agree).

RESULTS: 39 patients with ALS (age 66 ± 10 years, median time from diagnosis = 6 months) and 22 caregivers were enrolled. 32 patients had a PC consultation (30 were virtual). Patients and caregivers agreed with statements that the PC consult was helpful (mean ± SD = 4.54 ± 0.60, range = 3-5) and they would recommend PC to others with ALS (4.59 ± 0.59, range = 3-5). Participants disagreed with statements that the consult would have been better later in disease course (1.87 ± 0.80, range = 1-4) and that it took too much time/energy (1.44 ± 0.85, range = 1-4). Average ALSSQOL-R scores worsened significantly over time. HADS and ALSSQOL-R scores did not significantly differ between groups receiving and not receiving PC.

CONCLUSION: Patients with ALS and their caregivers found virtual PC consultations beneficial irrespective of disease duration or severity. Offering routine PC to all patients with ALS is feasible and should be considered as part of standard care.

CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT04257760, identifier NCT04257760.}, } @article {pmid37779364, year = {2024}, author = {Matveeva, A and Watters, O and Rukhadze, A and Khemka, N and Gentile, D and Perez, IF and Llorente-Folch, I and Farrell, C and Lo Cacciato, E and Jackson, J and Piazzesi, A and Wischhof, L and Woods, I and Halang, L and Hogg, M and Muñoz, AG and Dillon, ET and Matallanas, D and Arijs, I and Lambrechts, D and Bano, D and Connolly, NMC and Prehn, JHM}, title = {Integrated analysis of transcriptomic and proteomic alterations in mouse models of ALS/FTD identify early metabolic adaptions with similarities to mitochondrial dysfunction disorders.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {25}, number = {1-2}, pages = {135-149}, doi = {10.1080/21678421.2023.2261979}, pmid = {37779364}, issn = {2167-9223}, mesh = {Mice ; Animals ; Humans ; *Frontotemporal Dementia/metabolism ; *Amyotrophic Lateral Sclerosis/pathology ; Proteomics ; *Neurodegenerative Diseases ; *Pick Disease of the Brain ; Mice, Transgenic ; *Mitochondrial Diseases ; Gene Expression Profiling ; RNA, Messenger ; }, abstract = {OBJECTIVE: Sporadic and familial amyotrophic lateral sclerosis (ALS) is a fatal progressive neurodegenerative disease that results in loss of motor neurons and, in some patients, associates with frontotemporal dementia (FTD). Apart from the accumulation of proteinaceous deposits, emerging literature indicates that aberrant mitochondrial bioenergetics may contribute to the onset and progression of ALS/FTD. Here we sought to investigate the pathophysiological signatures of mitochondrial dysfunction associated with ALS/FTD.

METHODS: By means of label-free mass spectrometry (MS) and mRNA sequencing (mRNA-seq), we report pre-symptomatic changes in the cortices of TDP-43 and FUS mutant mouse models. Using tissues from transgenic mouse models of mitochondrial diseases as a reference, we performed comparative analyses and extracted unique and common mitochondrial signatures that revealed neuroprotective compensatory mechanisms in response to early damage.

RESULTS: In this regard, upregulation of both Acyl-CoA Synthetase Long-Chain Family Member 3 (ACSL3) and mitochondrial tyrosyl-tRNA synthetase 2 (YARS2) were the most representative change in pre-symptomatic ALS/FTD tissues, suggesting that fatty acid beta-oxidation and mitochondrial protein translation are mechanisms of adaptation in response to ALS/FTD pathology.

CONCLUSIONS: Together, our unbiased integrative analyses unveil novel molecular components that may influence mitochondrial homeostasis in the earliest phase of ALS.}, } @article {pmid37777552, year = {2023}, author = {Ometto, JP and Gorgens, EB and de Souza Pereira, FR and Sato, L and de Assis, MLR and Cantinho, R and Longo, M and Jacon, AD and Keller, M}, title = {A biomass map of the Brazilian Amazon from multisource remote sensing.}, journal = {Scientific data}, volume = {10}, number = {1}, pages = {668}, pmid = {37777552}, issn = {2052-4463}, mesh = {*Biomass ; Brazil ; Carbon/analysis ; *Forests ; *Remote Sensing Technology/methods ; Tropical Climate ; }, abstract = {The Amazon Forest, the largest contiguous tropical forest in the world, stores a significant fraction of the carbon on land. Changes in climate and land use affect total carbon stocks, making it critical to continuously update and revise the best estimates for the region, particularly considering changes in forest dynamics. Forest inventory data cover only a tiny fraction of the Amazon region, and the coverage is not sufficient to ensure reliable data interpolation and validation. This paper presents a new forest above-ground biomass map for the Brazilian Amazon and the associated uncertainty both with a resolution of 250 meters and baseline for the satellite dataset the year of 2016 (i.e., the year of the satellite observation). A significant increase in data availability from forest inventories and remote sensing has enabled progress towards high-resolution biomass estimates. This work uses the largest airborne LiDAR database ever collected in the Amazon, mapping 360,000 km[2] through transects distributed in all vegetation categories in the region. The map uses airborne laser scanning (ALS) data calibrated by field forest inventories that are extrapolated to the region using a machine learning approach with inputs from Synthetic Aperture Radar (PALSAR), vegetation indices obtained from the Moderate-Resolution Imaging Spectroradiometer (MODIS) satellite, and precipitation information from the Tropical Rainfall Measuring Mission (TRMM). A total of 174 field inventories geolocated using a Differential Global Positioning System (DGPS) were used to validate the biomass estimations. The experimental design allowed for a comprehensive representation of several vegetation types, producing an above-ground biomass map varying from a maximum value of 518 Mg ha[-1], a mean of 174 Mg ha[-1], and a standard deviation of 102 Mg ha[-1]. This unique dataset enabled a better representation of the regional distribution of the forest biomass and structure, providing further studies and critical information for decision-making concerning forest conservation, planning, carbon emissions estimate, and mechanisms for supporting carbon emissions reductions.}, } @article {pmid37776851, year = {2023}, author = {Tsioras, K and Smith, KC and Edassery, SL and Garjani, M and Li, Y and Williams, C and McKenna, ED and Guo, W and Wilen, AP and Hark, TJ and Marklund, SL and Ostrow, LW and Gilthorpe, JD and Ichida, JK and Kalb, RG and Savas, JN and Kiskinis, E}, title = {Analysis of proteome-wide degradation dynamics in ALS SOD1 iPSC-derived patient neurons reveals disrupted VCP homeostasis.}, journal = {Cell reports}, volume = {42}, number = {10}, pages = {113160}, pmid = {37776851}, issn = {2211-1247}, support = {S10 OD032464/OD/NIH HHS/United States ; R01 AG078796/AG/NIA NIH HHS/United States ; R01 NS134166/NS/NINDS NIH HHS/United States ; R21 NS107761/NS/NINDS NIH HHS/United States ; R01 NS097850/NS/NINDS NIH HHS/United States ; R01 NS124802/NS/NINDS NIH HHS/United States ; R01 NS104219/NS/NINDS NIH HHS/United States ; R01 NS122908/NS/NINDS NIH HHS/United States ; R01 NS096746/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Humans ; *Amyotrophic Lateral Sclerosis/genetics/metabolism ; Superoxide Dismutase-1/genetics/metabolism ; Proteome/metabolism ; Valosin Containing Protein/metabolism ; *Induced Pluripotent Stem Cells/metabolism ; Caenorhabditis elegans/metabolism ; Motor Neurons/metabolism ; Homeostasis ; Mutation ; }, abstract = {Mutations in SOD1 cause amyotrophic lateral sclerosis (ALS) through gain-of-function effects, yet the mechanisms by which misfolded mutant SOD1 (mutSOD1) protein impairs human motor neurons (MNs) remain unclear. Here, we use induced-pluripotent-stem-cell-derived MNs coupled to metabolic stable isotope labeling and mass spectrometry to investigate proteome-wide degradation dynamics. We find several proteins, including the ALS-causal valosin-containing protein (VCP), which predominantly acts in proteasome degradation and autophagy, that degrade slower in mutSOD1 relative to isogenic control MNs. The interactome of VCP is altered in mutSOD1 MNs in vitro, while VCP selectively accumulates in the affected motor cortex of ALS-SOD1 patients. Overexpression of VCP rescues mutSOD1 toxicity in MNs in vitro and in a C. elegans model in vivo, in part due to its ability to modulate the degradation of insoluble mutSOD1. Our results demonstrate that VCP contributes to mutSOD1-dependent degeneration, link two distinct ALS-causal genes, and highlight selective protein degradation impairment in ALS pathophysiology.}, } @article {pmid37776476, year = {2023}, author = {Ocharán-Mercado, A and Loaeza-Loaeza, J and Castro-Coronel, Y and Acosta-Saavedra, LC and Hernández-Kelly, LC and Hernández-Sotelo, D and Ortega, A}, title = {RNA-Binding Proteins: A Role in Neurotoxicity?.}, journal = {Neurotoxicity research}, volume = {41}, number = {6}, pages = {681-697}, pmid = {37776476}, issn = {1476-3524}, mesh = {Humans ; Aged ; *Neurodegenerative Diseases/metabolism ; RNA-Binding Proteins/metabolism ; Neurons/metabolism ; *Frontotemporal Dementia ; *Amyotrophic Lateral Sclerosis/metabolism ; }, abstract = {Despite sustained efforts to treat neurodegenerative diseases, little is known at the molecular level to understand and generate novel therapeutic approaches for these malignancies. Therefore, it is not surprising that neurogenerative diseases are among the leading causes of death in the aged population. Neurons require sophisticated cellular mechanisms to maintain proper protein homeostasis. These cells are generally sensitive to loss of gene expression control at the post-transcriptional level. Post-translational control responds to signals that can arise from intracellular processes or environmental factors that can be regulated through RNA-binding proteins. These proteins recognize RNA through one or more RNA-binding domains and form ribonucleoproteins that are critically involved in the regulation of post-transcriptional processes from splicing to the regulation of association of the translation machinery allowing a relatively rapid and precise modulation of the transcriptome. Neurotoxicity is the result of the biological, chemical, or physical interaction of agents with an adverse effect on the structure and function of the central nervous system. The disruption of the proper levels or function of RBPs in neurons and glial cells triggers neurotoxic events that are linked to neurodegenerative diseases such as spinal muscular atrophy (SMA), amyotrophic lateral sclerosis (ALS), fragile X syndrome (FXS), and frontotemporal dementia (FTD) among many others. The connection between RBPs and neurodegenerative diseases opens a new landscape for potentially novel therapeutic targets for the intervention of these neurodegenerative pathologies. In this contribution, a summary of the recent findings of the molecular mechanisms involved in the plausible role of RBPs in RNA processing in neurodegenerative disease is discussed.}, } @article {pmid37774774, year = {2023}, author = {Gschwendtberger, T and Thau-Habermann, N and von der Ohe, J and Luo, T and Hass, R and Petri, S}, title = {Protective effects of EVs/exosomes derived from permanently growing human MSC on primary murine ALS motor neurons.}, journal = {Neuroscience letters}, volume = {816}, number = {}, pages = {137493}, doi = {10.1016/j.neulet.2023.137493}, pmid = {37774774}, issn = {1872-7972}, mesh = {Mice ; Humans ; Animals ; *Amyotrophic Lateral Sclerosis/metabolism ; *Exosomes/metabolism ; Antioxidants/pharmacology ; Motor Neurons/metabolism ; *Mesenchymal Stem Cells/metabolism ; }, abstract = {In recent years, the neuroprotective potential of mesenchymal stroma-/stem-like cells (MSC) as well as of MSC-derived extracellular vesicles (EVs) like exosomes has been intensively explored. This included preclinical evaluation regarding treatment of neurodegenerative disorders such as the fatal motor neuron disease amyotrophic Lateral Sclerosis (ALS). Several studies have reported that MSC-derived exosomes can stimulate tissue regeneration and reduce inflammation. MSC release EVs and trophic factors and thereby modify cell-to-cell communication. These cell-free products may protect degenerating motor neurons (MNs) and represent a potential therapeutic approach for ALS. In the present study we investigated the effects of exosomes derived from a permanently growing MSC line on both, wild type and ALS (SOD1[G93A] transgenic) primary motor neurons. Following application in a normal and stressed environment we could demonstrate beneficial effects of MSC exosomes on neurite growth and morphology indicating the potential for further preclinical evaluation and clinical therapeutic development. Investigation of gene expression profiles detected transcripts of several antioxidant and anti-inflammatory genes in MSC exosomes. Characterization of their microRNA (miRNA) content revealed miRNAs capable of regulating antioxidant and anti-apoptotic pathways.}, } @article {pmid37774738, year = {2023}, author = {Stipancic, KL and Golzy, M and Zhao, Y and Pinkerton, L and Rohl, A and Kuruvilla-Dugdale, M}, title = {Improving Perceptual Speech Ratings: The Effects of Auditory Training on Judgments of Dysarthric Speech.}, journal = {Journal of speech, language, and hearing research : JSLHR}, volume = {66}, number = {11}, pages = {4236-4258}, pmid = {37774738}, issn = {1558-9102}, support = {R15 DC016383/DC/NIDCD NIH HHS/United States ; R21 DC019952/DC/NIDCD NIH HHS/United States ; }, mesh = {Humans ; Dysarthria/therapy ; *Speech Perception ; Judgment ; Reproducibility of Results ; *Amyotrophic Lateral Sclerosis ; Speech Intelligibility ; Speech Production Measurement ; *Parkinson Disease/complications ; }, abstract = {PURPOSE: Auditory training has been shown to reduce rater variability in perceptual voice assessment. Because rater variability is also a central issue in the auditory-perceptual assessment of dysarthria, this study sought to determine if training produces a meaningful change in rater reliability, criterion validity, and scaling magnitude of four features: overall speech impairment, articulatory imprecision, monotony, and slow rate.

METHOD: Forty-four nonexperts randomized to training and nontraining listener groups completed a pretest and posttest. Only the former group underwent auditory training between pre- and posttests. For both testing and training, listeners rated samples from speakers with amyotrophic lateral sclerosis (ALS), speakers with Parkinson's disease (PD), and neurologically healthy control speakers using separate visual analog scales (VASs) for each of the four features. Intraclass correlation coefficients were used to compare inter- and intrarater reliability between pre- and posttest for both listener groups. For criterion validity, severity ratings from the two nonexpert listener groups were compared to those of two experienced listeners for all four features. To determine changes in scaling magnitude, raw VAS scores for each feature were compared from pre- to posttest within the two nonexpert listener groups. Scaling changes were also compared between the two listener groups for the pre- and posttest conditions.

RESULTS AND CONCLUSIONS: In the training group, a meaningful improvement in interrater reliability was observed for some features in all three speaker groups, but not in the nontraining group. In contrast, for intrarater reliability, in the nontraining group, a meaningful improvement was observed for many features in all three speaker groups, but only for PD monotony and slow rate in the training group. All ratings from the nonexpert listeners were valid except for monotony. Raw VAS scores did not meaningfully change from pre- to posttest for any of the features, but there was a trend toward lower scores posttraining, mainly for the ALS samples. Modifications to the auditory training paradigm to further improve reliability and validity, along with future goals for optimizing training, are discussed.}, } @article {pmid37773576, year = {2024}, author = {Aiello, EN and Solca, F and Torre, S and Gentile, F and Scheveger, F and Olivero, M and Colombo, E and Maranzano, A and Manzoni, M and Morelli, C and Doretti, A and Verde, F and Silani, V and Ticozzi, N and Poletti, B}, title = {Frontotemporal-spectrum disorders and functional independence in non-demented ALS patients.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {45}, number = {3}, pages = {1087-1095}, pmid = {37773576}, issn = {1590-3478}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis ; Activities of Daily Living ; Functional Status ; Neuropsychological Tests ; *Frontotemporal Dementia ; Cognition ; }, abstract = {BACKGROUND: The present study aimed at determining whether, net of motor confounders, neuropsychological features affect functional independence (FI) in activities of daily living (ADLs) in non-demented amyotrophic lateral sclerosis (ALS) patients.

METHODS: N = 88 ALS patients without frontotemporal dementia were assessed for FI-Katz's Basic ADL Scale (BADL) and Lawton-Brody's Instrumental ADL Scale (IADL)-, cognition-Edinburgh Cognitive and Behavioural ALS Screen (ECAS)-and behaviour-Beaumont Behavioural Inventory and Dimensional Apathy Scale. The association between cognitive and behavioural measures and BADL/IADL scores was assessed by covarying for demographics, anxiety and depression levels, disease duration and motor confounders-i.e. ALS Functional Rating Scale-Revised (ALSFRS-R) scores, progression rate and both King's and Milano-Torino stages.

RESULTS: Higher scores on the ECAS-Language were associated with higher IADL scores (p = 0.005), whilst higher apathetic features-as measured by the Dimensional Apathy Scale (DAS)-were inversely related to the BADL (p = 0.003). Whilst IADL scores were related to all ECAS-Language tasks, the DAS-Initiation was the only subscale associated with BADL scores. Patients with abnormal ECAS-Language (p = 0.023) and DAS (p = 0.008) scores were more functionally dependent than those without.

DISCUSSION: Among non-motor features, language changes and apathetic features detrimentally affect FI in non-demented ALS patients.}, } @article {pmid37773166, year = {2023}, author = {Aguilar-Vázquez, CA and Gallardo-González, LI and Raymundo-Carrillo, AD and Reyes-Sosa, LC and Martínez-Romo, ES}, title = {[Parkinson-dementia and amyotrophic lateral sclerosis association (complex of Guam). Diagnostic challenge, Mexican patient].}, journal = {Revista medica del Instituto Mexicano del Seguro Social}, volume = {61}, number = {5}, pages = {677-684}, pmid = {37773166}, issn = {2448-5667}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/complications/diagnosis/epidemiology ; *Parkinson Disease/complications/pathology ; *Dementia/complications/epidemiology/pathology ; *Neurodegenerative Diseases ; Guam/epidemiology ; *Parkinsonian Disorders/etiology/complications ; }, abstract = {BACKGROUND: The Amyotrophic Lateral Sclerosis-Parkinsonism-Dementia Complex (ALS-PDC) was first described in the islands of Guam. This pathology presented its peak incidence in the 1950s. Due to the rarity of the association, we report a clinical case with this complex. The objective was to describe the nosological and pathogenic implications of these neurodegenerative disorder, since they are not frequent to find in our population.

CLINICAL CASE: We present a case of Latinoamerican origin who initially manifested systemic symptoms of more than 6 years of evolution, with subsequent cognitive alterations. Later, patient began with gait disturbances and motor symptoms suggestive of parkinsonism with atypical data and data of motor neurone disease (MND). More studies were carried out and confirmed findings compatible with upper and lower motor neuron involvement. A mutation in the POLG gene was observed, related to mitochondrial depletion syndrome.

CONCLUSION: Despite the knowledge of this association, it is an entity whose clinical diagnosis could be very difficult to achieve. In addition, molecular mechanisms have not been fully identified, the most common genes related to Parkinsonism and ALS have been excluded, and even attempts to locate the locus were made, without achieving accurate results. Unfortunately, being a neurodegenerative disease, the prognosis is fatal, with no disease-modifying treatment.}, } @article {pmid37772684, year = {2023}, author = {Ali, Z and Godoy-Corchuelo, JM and Martins-Bach, AB and Garcia-Toledo, I and Fernández-Beltrán, LC and Nair, RR and Spring, S and Nieman, BJ and Jimenez-Coca, I and Bains, RS and Forrest, H and Lerch, JP and Miller, KL and Fisher, EMC and Cunningham, TJ and Corrochano, S}, title = {Mutation in the FUS nuclear localisation signal domain causes neurodevelopmental and systemic metabolic alterations.}, journal = {Disease models & mechanisms}, volume = {16}, number = {10}, pages = {}, pmid = {37772684}, issn = {1754-8411}, support = {FISHER/APR14/874-792/MNDA_/Motor Neurone Disease Association/United Kingdom ; G0801110/MRC_/Medical Research Council/United Kingdom ; MR/L021056/1/MRC_/Medical Research Council/United Kingdom ; MC_EX_MR/N501931/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Mice ; Animals ; *Amyotrophic Lateral Sclerosis/pathology ; Nuclear Localization Signals/genetics/metabolism ; RNA-Binding Protein FUS/genetics/metabolism ; Mutation/genetics ; Neurons/metabolism ; }, abstract = {Variants in the ubiquitously expressed DNA/RNA-binding protein FUS cause aggressive juvenile forms of amyotrophic lateral sclerosis (ALS). Most FUS mutation studies have focused on motor neuron degeneration; little is known about wider systemic or developmental effects. We studied pleiotropic phenotypes in a physiological knock-in mouse model carrying the pathogenic FUSDelta14 mutation in homozygosity. RNA sequencing of multiple organs aimed to identify pathways altered by the mutant protein in the systemic transcriptome, including metabolic tissues, given the link between ALS-frontotemporal dementia and altered metabolism. Few genes were commonly altered across all tissues, and most genes and pathways affected were generally tissue specific. Phenotypic assessment of mice revealed systemic metabolic alterations related to the pathway changes identified. Magnetic resonance imaging brain scans and histological characterisation revealed that homozygous FUSDelta14 brains were smaller than heterozygous and wild-type brains and displayed significant morphological alterations, including a thinner cortex, reduced neuronal number and increased gliosis, which correlated with early cognitive impairment and fatal seizures. These findings show that the disease aetiology of FUS variants can include both neurodevelopmental and systemic alterations.}, } @article {pmid37770379, year = {2023}, author = {Souza, INO and Roychaudhuri, R and de Belleroche, J and Mothet, JP}, title = {d-Amino acids: new clinical pathways for brain diseases.}, journal = {Trends in molecular medicine}, volume = {29}, number = {12}, pages = {1014-1028}, doi = {10.1016/j.molmed.2023.09.001}, pmid = {37770379}, issn = {1471-499X}, mesh = {Humans ; *Amino Acids/metabolism ; Critical Pathways ; Central Nervous System/metabolism ; Brain/metabolism ; *Alzheimer Disease/metabolism ; }, abstract = {Free d-amino acids (d-AAs) are emerging as a novel and important class of signaling molecules in many organs, including the brain and endocrine systems. There has been considerable progress in our understanding of the fundamental roles of these atypical messengers, with increasingly recognized implications in a wide range of neuropathologies, including schizophrenia (SCZ), epilepsy, Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), substance abuse, and chronic pain, among others. Research has enabled the discovery that d-serine, d-aspartate and more recently d-cysteine are essential for the healthy development and function of the central nervous system (CNS). We discuss recent progress that has profoundly transformed our vision of numerous physiological processes but has also shown how d-AAs are now offering therapeutic promise in clinical settings for several human diseases.}, } @article {pmid37770137, year = {2023}, author = {Bivehed, E and Hellman, B and Fan, Y and Haglöf, J and Buratovic, S}, title = {DNA integrity under alkaline conditions: An investigation of factors affecting the comet assay.}, journal = {Mutation research. Genetic toxicology and environmental mutagenesis}, volume = {891}, number = {}, pages = {503680}, doi = {10.1016/j.mrgentox.2023.503680}, pmid = {37770137}, issn = {1879-3592}, mesh = {Humans ; *Comet Assay/methods ; DNA ; DNA Damage ; DNA Repair ; Hydrogen-Ion Concentration ; }, abstract = {The effect of pH on DNA integrity was assessed using a three-step approach. The comet assay was used on a whole genome level, with three different protocols: neutral (no alkaline unwinding), flash (pH 12.5 with 2.5 min unwinding), and the conventional alkaline protocol (pH>13 with 40 min unwinding). Real-time quantitative PCR (RT-qPCR) was then used to study the isolated DNA, revealing that gene amplification decreased with increasing pH, indicating DNA degradation. Specially designed molecular beacons were used to examine DNA at the molecular level, with or without alkali-labile site (ALS) insertions. At pH 12.5, fluorescence in the hairpins with ALS started to increase after 30 min, while at pH> 13, this increase was already observed after 5 min, indicating a significant increase in DNA strand breaks. Liquid chromatography analysis was also used, demonstrating that the hairpins remained intact up to pH 10, even after 1 h exposure, whereas, at pH 12.5, partial conversion into strand breaks occurred after 30 min. At pH> 13, the hairpins were almost completely degraded after 30 min. The flash protocol effectively detects DNA single- and double-strand breaks and identified these damages after 2.5 min of alkaline treatment at pH 12.5. When the hairpins were exposed to pH 12.5 for 60 min, ALS were converted to strand breaks, demonstrating the sensitivity of this approach to detect changes in DNA structure. These findings indicate that pH poses a substantial risk to DNA integrity, leading to significantly higher background levels of DNA damage compared to conditions closer to neutrality. Our study demonstrates the importance of understanding the influence of pH on DNA stability and provides insights into risks associated with alkaline environments, especially at pH> 13.}, } @article {pmid37769591, year = {2023}, author = {Pazian Martins, M and González-Salazar, C and de Lima, FD and Bernardes Leoni, T and R M Martinez, A and Nunes Gonçalves, JP and Nucci, A and Cavalcante França, M}, title = {Autonomic function in sporadic and familial ALS type 8.}, journal = {Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology}, volume = {155}, number = {}, pages = {68-74}, doi = {10.1016/j.clinph.2023.08.006}, pmid = {37769591}, issn = {1872-8952}, abstract = {OBJECTIVE: To characterize and compare autonomic function in patients with sporadic (sALS) and familial ALS type 8 (fALS8).

METHODS: We selected 11 patients with sALS (7 men), 14 with fALS8 (8 men) and 26 controls (15 men). All groups were gender and age-matched. For each subject, Scale for Outcomes in Parkinson's Disease for Autonomic Symptoms (SCOPA-AUT) was applied and data from heart rate variability, Quantitative Sudomotor Axon Reflex Test (QSART) and skin sympathetic response (SSR) were collected. These data were compared across groups using nonparametric tests. P-values < 0.05 were considered significant.

RESULTS: SCOPA-AUT revealed predominant clinical complaints in thermoregulatory, pupillomotor and sexual domains in fALS8 relative to sALS as well as controls. Neurophysiological tests demonstrated significant differences in Valsalva ratio, Expiratory:Inspiratory index and RR minimum values in both ALS groups relative to controls. Sudomotor dysfunction was also observed in sALS and fALS8 groups, as shown by reduced medial forearm and foot QSART volumes and absence of SSR in lower limbs.

CONCLUSIONS: Dysautonomia - cardiac and sudomotor - is part of the phenotype in sALS and fALS8. The profile of autonomic symptoms, however, is different in each group.

SIGNIFICANCE: Patients with fALS8 and sALS have autonomic dysfunction involving both sympathetic and parasympathetic divisions.}, } @article {pmid37768998, year = {2023}, author = {Abraham, A and Fainmesser, Y and Drory, VE and Bril, V}, title = {Quantitative sonographic assessment of muscle thickness and fasciculations distribution is a sensitive tool for neuromuscular disorders.}, journal = {PloS one}, volume = {18}, number = {9}, pages = {e0292123}, pmid = {37768998}, issn = {1932-6203}, mesh = {Humans ; Fasciculation/diagnostic imaging ; Muscle, Skeletal/diagnostic imaging ; *Amyotrophic Lateral Sclerosis/diagnostic imaging ; Electromyography ; *Neuromuscular Diseases/diagnostic imaging ; *Muscular Diseases ; Ultrasonography ; *Polyneuropathies/diagnostic imaging ; }, abstract = {INTRODUCTION: Loss of muscle thickness can be demonstrated in a wide spectrum of neuromuscular disorders, while fasciculations are more frequent in amyotrophic lateral sclerosis (ALS). In the current study, we aimed to determine the sensitivity and specificity of quantitative sonographic assessment of muscle thickness and the presence of fasciculations for diagnosing various neuromuscular disorders.

METHODS: The thickness and the presence of fasciculations in eight muscles were determined by sonography in patients with myopathy (22), polyneuropathy (36), ALS (91), and spinal muscular atrophy (SMA) (31) and compared to normative values determined in 65 heathy control subjects.

RESULTS: Reduced muscle thickness in at least one relaxed muscle showed 92-100% sensitivity for diagnosing a neuromuscular disease, with a specificity of 85% for differentiating patients from heathy controls (AUC = 0.90). Subtracting distal from proximal muscle thickness may differentiate between myopathy and polyneuropathy. Fasciculations in ≥1 proximal muscle showed good diagnostic accuracy (AUC = 0.87) for diagnosing ALS.

DISCUSSION: Sonographic assessment of muscle thickness is a sensitive tool for diagnosing a wide spectrum of neuromuscular diseases, and may facilitate diagnosis even in patients with normal strength on neurological examination, while the presence of fasciculations in proximal muscles may facilitate ALS diagnosis.}, } @article {pmid37768719, year = {2023}, author = {Aksoy, ME and Özkan, AE and Kitapcioglu, D and Usseli, T}, title = {Comparing the Outcomes of Virtual Reality-Based Serious Gaming and Lecture-Based Training for Advanced Life Support Training: Randomized Controlled Trial.}, journal = {JMIR serious games}, volume = {11}, number = {}, pages = {e46964}, pmid = {37768719}, issn = {2291-9279}, abstract = {BACKGROUND: Simulation-based Advanced Cardiac Life Support (ACLS) or Advanced Life Support (ALS) training for health care professionals is important worldwide for saving lives. Virtual reality (VR)-based serious gaming can be an alternative modality to be used as a part of simulation-based ALS training.

OBJECTIVE: The aim of this study is to investigate whether a VR-based ALS serious game module can replace classroom-based ALS lectures, the latter being part of existing conventional ALS training protocols in addition to skills training.

METHODS: Participants were students from Acibadem Mehmet Ali Aydinlar University's Vocational School for Anesthesiology (N=29) randomly divided into 2 groups with 15 (conventional training group) and 14 (VR-based training group) participants each. Participants in the conventional training group had to complete the pretest consisting of multiple-choice questions at the beginning of the study. Afterward, they took part in an interactive classroom-based ALS lecture. The next step involved skills training with task trainers to teach them compression skills. Following this, the conventional training group was divided into Code Blue teams, each consisting of 5 participants for the simulation session. Two independent instructors evaluated video recordings in terms of technical and nontechnical skills. The score acquired from the manikin-based simulation session was considered the main performance indicator in this study to measure the learning outcome. A similar workflow was used for the VR-based training group, but this group was trained with the VR-based ALS serious game module instead of the theoretical lecture. The final stage of the study involved completing the posttest consisting of multiple-choice questions. A preference survey was conducted among the study participants. Mann-Whitney U and Wilcoxon signed-rank tests were used to analyze the 2 groups' performances in this study.

RESULTS: The improvement in posttest results compared with pretest results was significant in the conventional training group (P=.002). Hands-on technical scores of the conventional training group were higher than those of the VR-based training group during manikin-based simulation, but total scores, including those for technical and crisis resource management skills, acquired from the manikin-based simulation session did not reveal any significant difference between the 2 groups. The results of the VR preference survey revealed that the majority of the participants prefer VR-based serious game-based training instead of classroom lectures.

CONCLUSIONS: Although hands-on technical scores of the conventional training group during the manikin-based simulation session were higher than those of the VR-based training group, both groups' total performance scores, including those for technical and crisis resource management skills, did not differ significantly. The preference survey reveals that the majority of the participants would prefer a VR-based ALS serious gaming module instead of lecture-based training. Further studies are required to reveal the learning outcome of VR-based ALS serious gaming.

TRIAL REGISTRATION: ClinicalTrials.gov NCT05798910; https://clinicaltrials.gov/study/NCT05798910.}, } @article {pmid37768183, year = {2023}, author = {Trajano, GS and Orssatto, LBR and McCombe, PA and Rivlin, W and Tang, L and Henderson, RD}, title = {Longitudinal changes in intrinsic motoneuron excitability in amyotrophic lateral sclerosis are dependent on disease progression.}, journal = {The Journal of physiology}, volume = {601}, number = {21}, pages = {4723-4735}, doi = {10.1113/JP285181}, pmid = {37768183}, issn = {1469-7793}, mesh = {Humans ; Animals ; Mice ; *Amyotrophic Lateral Sclerosis ; Cross-Sectional Studies ; Superoxide Dismutase-1/genetics ; Motor Neurons/physiology ; Muscle, Skeletal ; Muscle Weakness ; Paresis ; Disease Progression ; }, abstract = {Increased amplitude of persistent inward currents (PICs) is observed in pre-symptomatic genetically modified SOD1 mice models of amyotrophic lateral sclerosis (ALS). However, at the symptomatic stage this reverses and there is a large reduction in PIC amplitude. It remains unclear whether these changes in PICs can be observed in humans, with cross-sectional studies in humans reporting contradictory findings. In people with ALS, we estimated the PIC contribution to self-sustained firing of motoneurons, using the paired-motor unit analysis to calculate the Δfrequency (ΔF), to compare the weaker and stronger muscles during the course of disease. We hypothesised that, with disease progression, ΔFs would relatively increase in the stronger muscles; and decline in the weaker muscles. Forty-three individuals with ALS were assessed in two occasions on average 17 weeks apart. Tibialis anterior high-density electromyograms were recorded during dorsiflexion (40% of maximal capacity) ramped contractions, followed by clinical tests. ∆F increased from 3.14 (2.57, 3.71) peaks per second (pps) to 3.55 (2.94, 4.17) pps on the stronger muscles (0.41 (0.041, 0.781) pps, standardised difference (d) = 0.287 (0.023, 0.552), P = 0.030). ∆F reduced from 3.38 (95% CI 2.92, 3.84) pps to 2.88 (2.40, 3.36) pps on the weaker muscles (-0.50 (-0.80, -0.21) pps, d = 0.353 (0.138, 0.567), P = 0.001). The ALSFRS-R score reduced 3.9 (2.3, 5.5) points. These data indicate that the contribution of PICs to motoneuron self-sustained firing increases over time in early stages of the disease when there is little weakness before decreasing as the disease progresses and muscle weakness exacerbates, in alignment with the findings from studies using SOD1 mice. KEY POINTS: Research on mouse model of amyotrophic lateral sclerosis (ALS) suggests that the amplitude of persistent inward currents (PICs) is increased in early stages before decreasing as the disease progresses. Cross-sectional studies in humans have reported contradictory findings with both higher and lower PIC contributions to motoneuron self-sustained firing. In this longitudinal (∼17 weeks) study we tracked changes in PIC contribution to motoneuron self-sustained firing, using the ΔF calculation (i.e. onset-offset hysteresis of motor unit pairs), in tibialis anterior muscles with normal strength and with clinical signs of weakness in people with ALS. ΔFs decreased over time in muscles with clinical signs of weakness. The PIC contribution to motoneuron self-sustained firing increases before the onset of muscle weakness, and subsequently decreases when muscle weakness progresses.}, } @article {pmid37767949, year = {2024}, author = {Liang, W and Liu, Y and Zhao, Y and Chen, Y and Yin, Y and Zhai, L and Li, Z and Gong, Z and Zhang, J and Zhang, M}, title = {Quantitative MRI Analysis of Brachial Plexus and Limb-Girdle Muscles in Upper Extremity Onset Amyotrophic Lateral Sclerosis.}, journal = {Journal of magnetic resonance imaging : JMRI}, volume = {60}, number = {1}, pages = {291-301}, doi = {10.1002/jmri.29027}, pmid = {37767949}, issn = {1522-2586}, support = {82271478//National Natural Science Foundation of China/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnostic imaging ; Female ; Male ; Middle Aged ; *Magnetic Resonance Imaging/methods ; *Brachial Plexus/diagnostic imaging ; *Upper Extremity/diagnostic imaging ; Retrospective Studies ; Aged ; Adult ; Muscle, Skeletal/diagnostic imaging ; }, abstract = {BACKGROUND: Recent evidence highlights the potential of axonal degeneration as a biomarker for amyotrophic lateral sclerosis (ALS) detection. However, the diagnostic potential of peripheral nerve axon changes in ALS remains unclear.

PURPOSE: To evaluate the diagnostic performance of quantitative MRI of the brachial plexus and limb-girdle muscles (LGMs) in patients with upper extremity onset of ALS.

STUDY TYPE: Retrospective.

POPULATION: 47 patients with upper extremity onset of ALS and 20 healthy volunteers.

FIELD STRENGTH/SEQUENCE: 3-T, three-dimensional sampling perfection with application-optimized contrasts using different flip angle evolutions with short-tau inversion recovery sequences, T2-weighted turbo spin-echo Dixon sequence.

ASSESSMENT: The cross-sectional area (CSA) and nerve-muscle T2 signal intensity ratio (nT2) of the bilateral brachial plexus as well as the CSA and fat fraction (FF) of the bilateral LGMs were assessed by two radiologists. Disease severity and clinical stage of ALS patients were assessed by two neurologists.

STATISTICAL TESTS: Student's t-test, Wilcoxon rank-sum test, binary logistic regression, interclass correlation coefficient, receiver operating characteristic analysis, and correlation analysis were performed for MRI quantitative metrics and clinical variables. Significance level: P < 0.05.

RESULTS: In the affected limbs of patients with ALS, the CSA of the brachial plexus roots, trunks, and cords and the nT2 values of the brachial plexus trunks were significantly smaller than in the healthy controls. In the LGMs, the affected limbs of ALS showed significantly smaller CSA and higher FF than controls. The model containing parameters such as brachial plexus trunk CSA, subscapularis CSA, infraspinatus CSA, and subscapularis FF had excellent diagnostic efficacy for ALS. Additionally, increased subscapularis FF and supraspinatus FF were correlated with disease severity, and subscapularis CSA was negatively correlated with the clinical stage.

DATA CONCLUSION: Brachial plexus thinning, LGM atrophy, and fatty infiltration might serve as MRI-derived biomarkers for ALS with upper extremity onset.

LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY: Stage 2.}, } @article {pmid37767237, year = {2023}, author = {Trofimov, A and Pavlov, D and Goswami, A and Gorlova, A and Chaprov, K and Umriukhin, A and Kalueff, A and Deykin, A and Lesch, KP and Anthony, DC and Strekalova, T}, title = {Lipopolysaccharide triggers exacerbated microglial activation, excessive cytokine release and behavioural disturbances in mice with truncated Fused-in-Sarcoma Protein (FUS).}, journal = {Brain, behavior, & immunity - health}, volume = {33}, number = {}, pages = {100686}, pmid = {37767237}, issn = {2666-3546}, abstract = {CNS inflammation, including microglial activation, in response to peripheral infections are known to contribute to the pathology of both familial and sporadic neurodegenerative disease. The relationship between Fused-in-Sarcoma Protein (FUS)-mediated disease in the transgenic FUS[1-359] animals and the systemic inflammatory response have not been explored. Here, we investigated microglial activation, inflammatory gene expression and the behavioural responses to lipopolysaccharide-induced (LPS; 0.1 mg/kg) systemic inflammation in the FUS[1-359] transgenic mice. The pathology of these mice recapitulates the key features of mutant FUS-associated familial frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). Here, pre-symptomatic 8-week-old mutant or wild type controls were challenged with LPS or with saline and sucrose intake, novel cage exploration, marble burying and swimming behaviours were analyzed. The level of pro-inflammatory gene expression was also determined, and microglial activation was evaluated. In chronic experiments, to discover whether the LPS challenge would affect the onset of ALS-like paralysis, animals were evaluated for clinical signs from 5 to 7 weeks post-injection. Compared to controls, acutely challenged FUS[1-359]-tg mice exhibited decreased sucrose intake and increased floating behaviours. The FUS[1-359]-tg mice exhibited an increase in immunoreactivity for Iba1-positive cells in the prefrontal cortex and ventral horn of the spinal cord, which was accompanied by increased expression of interleukin-1β, tumour necrosis factor, cyclooxygenase-(COX)-1 and COX-2. However, the single LPS challenge did not alter the time to development of paralysis in the FUS[1-359]-tg mice. Thus, while the acute inflammatory response was enhanced in the FUS mutant animals, it did not have a lasting impact on disease progression.}, } @article {pmid37767023, year = {2023}, author = {Ayoubi, R and Alshafie, W and Southern, K and McPherson, PS and Laflamme, C and , }, title = {The identification of high-performing antibodies for Coiled-coil-helix-coiled-coil-helix domain containing protein 10 (CHCHD10) for use in Western Blot, immunoprecipitation and immunofluorescence.}, journal = {F1000Research}, volume = {12}, number = {}, pages = {403}, pmid = {37767023}, issn = {2046-1402}, mesh = {Humans ; *Fluorescent Antibody Technique/methods ; *Immunoprecipitation/methods ; *Mitochondrial Proteins/immunology ; *Blotting, Western ; *Antibodies/immunology ; HEK293 Cells ; }, abstract = {CHCHD10 is a mitochondrial protein, implicated in the regulation of mitochondrial morphology and cristae structure, as well as the maintenance of mitochondrial DNA integrity. Recently discovered to be associated with amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) in its mutant form, the scientific community would benefit from the availability of validated anti-CHCHD10 antibodies. In this study, we characterized four CHCHD10 commercial antibodies for Western Blot, immunoprecipitation, and immunofluorescence using a standardized experimental protocol based on comparing read-outs in knockout cell lines and isogenic parental controls. As this study highlights high-performing antibodies for CHCHD10, we encourage readers to use it as a guide to select the most appropriate antibody for their specific needs.}, } @article {pmid37766843, year = {2023}, author = {Olukoya, AO and Stires, H and Bahnassy, S and Persaud, S and Guerra, Y and Ranjit, S and Ma, S and Cruz, MI and Benitez, C and Rozeboom, AM and Ceuleers, H and Berry, DL and Jacobsen, BM and Raj, GV and Riggins, RB}, title = {Riluzole Suppresses Growth and Enhances Response to Endocrine Therapy in ER+ Breast Cancer.}, journal = {Journal of the Endocrine Society}, volume = {7}, number = {10}, pages = {bvad117}, pmid = {37766843}, issn = {2472-1972}, support = {T32 CA009686/CA/NCI NIH HHS/United States ; }, abstract = {BACKGROUND: Resistance to endocrine therapy in estrogen receptor-positive (ER+) breast cancer remains a significant clinical problem. Riluzole is FDA-approved for the treatment of amyotrophic lateral sclerosis. A benzothiazole-based glutamate release inhibitor with several context-dependent mechanism(s) of action, riluzole has shown antitumor activity in multiple malignancies, including melanoma, glioblastoma, and breast cancer. We previously reported that the acquisition of tamoxifen resistance in a cellular model of invasive lobular breast cancer is accompanied by the upregulation of GRM mRNA expression and growth inhibition by riluzole.

METHODS: We tested the ability of riluzole to reduce cell growth, alone and in combination with endocrine therapy, in a diverse set of ER+ invasive ductal and lobular breast cancer-derived cell lines, primary breast tumor explant cultures, and the estrogen-independent, ESR1-mutated invasive lobular breast cancer patient-derived xenograft model HCI-013EI.

RESULTS: Single-agent riluzole suppressed the growth of ER+ invasive ductal and lobular breast cancer cell lines in vitro, inducing a histologic subtype-associated cell cycle arrest (G0-G1 for ductal, G2-M for lobular). Riluzole induced apoptosis and ferroptosis and reduced phosphorylation of multiple prosurvival signaling molecules, including Akt/mTOR, CREB, and Fak/Src family kinases. Riluzole, in combination with either fulvestrant or 4-hydroxytamoxifen, additively suppressed ER+ breast cancer cell growth in vitro. Single-agent riluzole significantly inhibited HCI-013EI patient-derived xenograft growth in vivo, and the combination of riluzole plus fulvestrant significantly reduced proliferation in ex vivo primary breast tumor explant cultures.

CONCLUSION: Riluzole may offer therapeutic benefits in diverse ER+ breast cancers, including lobular breast cancer.}, } @article {pmid37766430, year = {2023}, author = {Cheng, W and Huang, J and Fu, XQ and Tian, WY and Zeng, PM and Li, Y and Luo, ZG}, title = {Intrathecal delivery of AAV-NDNF ameliorates disease progression of ALS mice.}, journal = {Molecular therapy : the journal of the American Society of Gene Therapy}, volume = {31}, number = {11}, pages = {3277-3289}, pmid = {37766430}, issn = {1525-0024}, mesh = {Animals ; Mice ; *Amyotrophic Lateral Sclerosis/genetics/therapy ; Dependovirus/genetics ; Disease Models, Animal ; Disease Progression ; Mice, Transgenic ; Motor Neurons/metabolism ; Nerve Growth Factors/metabolism ; *Neurodegenerative Diseases/metabolism ; Spinal Cord/metabolism ; Superoxide Dismutase-1/genetics/metabolism ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a uniformly lethal neurodegenerative disease characterized by progressive deterioration of motor neurons and neuromuscular denervation. Adeno-associated virus (AAV)-mediated delivery of trophic factors is being considered as a potential disease-modifying therapeutic avenue. Here we show a marked effect of AAV-mediated over-expression of neuron-derived neurotrophic factor (NDNF) on SOD1[G93A] ALS model mice. First, we adopt AAV-PHP.eB capsid to enable widespread expression of target proteins in the brain and spinal cord when delivered intrathecally. Then we tested the effects of AAV-NDNF on SOD1[G93A] mice at different stages of disease. Interestingly, AAV-NDNF markedly improved motor performance and alleviated weight loss when delivered at early post-symptomatic stage. Injection in the middle post-symptomatic stages still improved the locomotion ability, although it did not alleviate the loss of body weight. Injection in the late stage also extended the life span of SOD1[G93A] mice. Furthermore, NDNF expression promoted the survival of spinal motoneurons, reduced abnormal protein aggregation, and preserved the innervated neuromuscular functions. We further analyzed the signaling pathways of NDNF expression and found that it activates cell survival and growth-associated mammalian target of rapamycin signaling pathway and downregulates apoptosis-related pathways. Thus, intrathecally AAV-NDNF delivery has provided a potential strategy for the treatment of ALS.}, } @article {pmid37766226, year = {2023}, author = {Ayers, JI and Xu, G and Lu, Q and Dillon, K and Fromholt, S and Borchelt, DR}, title = {Multiple Factors Influence the Incubation Period of ALS Prion-like Transmission in SOD1 Transgenic Mice.}, journal = {Viruses}, volume = {15}, number = {9}, pages = {}, pmid = {37766226}, issn = {1999-4915}, support = {R01 NS092788/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Humans ; Mice ; Young Adult ; *Amyotrophic Lateral Sclerosis/genetics ; Mice, Transgenic ; Paralysis ; *Prions ; Superoxide Dismutase-1/genetics ; }, abstract = {Mutations in superoxide dismutase 1 (SOD1) that are associated with amyotrophic lateral sclerosis (ALS) cause its misfolding and aggregation. Prior studies have demonstrated that the misfolded conformation of ALS-SOD1 can template with naïve SOD1 "host proteins" to propagate, spread, and induce paralysis in SOD1 transgenic mice. These observations have advanced the argument that SOD1 is a host protein for an ALS conformer that is prion-like and experimentally transmissible. Here, we investigated the propagation of different isolates of G93A-SOD1 ALS conformers using a paradigm involving transmission to mice expressing human G85R-SOD1 fused to yellow fluorescent protein (G85R-SOD1:YFP). In these studies, we also utilized a newly developed line of mice in which the G85R-SOD1:YFP construct was flanked by loxp sites, allowing its temporal and spatial regulation. We used methods in which the G93A ALS conformers were injected into the sciatic nerve or hindlimb muscle of adult transgenic mice. We observed that the incubation period to paralysis varied significantly depending upon the source of inoculum containing misfolded G93A SOD1. Serial passage and selection produced stable isolates of G93A ALS conformers that exhibited a defined minimum incubation period of ~2.5 months when injected into the sciatic nerve of young adult mice. As expected, neuronal excision of the transgene in loxpG85R-SOD1:YFP mice blocked induction of paralysis by transmission of G93A ALS conformers. Our findings indicate that G93A ALS conformers capable of inducing disease require neuronal expression of a receptive host SOD1 protein for propagation, with a defined incubation period to paralysis.}, } @article {pmid37763163, year = {2023}, author = {Kortazar-Zubizarreta, I and Manero-Azua, A and Afonso-Agüera, J and Perez de Nanclares, G}, title = {C9ORF72 Gene GGGGCC Hexanucleotide Expansion: A High Clinical Variability from Amyotrophic Lateral Sclerosis to Frontotemporal Dementia.}, journal = {Journal of personalized medicine}, volume = {13}, number = {9}, pages = {}, pmid = {37763163}, issn = {2075-4426}, abstract = {The expanded GGGGCC hexanucleotide repeat (HRE) in the non-coding region of the C9ORF72 gene (C9ORF72-HRE) is the most common genetic cause of familial forms of amyotrophic lateral sclerosis (ALS), FTD, and concurrent ALS and FTD (ALS-FTD), in addition to contributing to the sporadic forms of these diseases. Both syndromes overlap not only genetically, but also sharing similar clinical and neuropathological findings, being considered as a spectrum. In this paper we describe the clinical-genetic findings in a Basque family with different manifestations within the spectrum, our difficulties in reaching the diagnosis, and a narrative review, carried out as a consequence, of the main features associated with C9ORF72-HRE. Family members underwent a detailed clinical assessment, neurological examination, and genetic analysis by repeat-primed PCR. We studied 10 relatives of a symptomatic carrier of the C9ORF72-HRE expansion. Two of them presented the expansion in the pathological range, one of them was symptomatic whereas the other one remained asymptomatic at 72 years. Given the great intrafamilial clinical variability of C9ORF72-HRE, the characterization of patients and family members with particular clinical and genetic subgroups within ALS and FTD becomes a bottleneck for medication development, in particular for genetically focused medicines for ALS and FTD.}, } @article {pmid37762807, year = {2023}, author = {Annunziata, A and Calabrese, C and Simioli, F and Coppola, A and Pierucci, P and Mariniello, DF and Fiorentino, G}, title = {Psychological Factors Influencing Adherence to NIV in Neuromuscular Patients Dependent on Non Invasive Mechanical Ventilation: Preliminary Results.}, journal = {Journal of clinical medicine}, volume = {12}, number = {18}, pages = {}, pmid = {37762807}, issn = {2077-0383}, abstract = {BACKGROUND: Non-invasive ventilation (NIV) is associated with improvement of both morbility and mortality in patients affected by neuromuscular diseases with chronic respiratory failure. Several studies have also shown that long-term NIV positively impacts the patient's quality of life and perception of disease status. Its effectiveness is likely related to the adherence to NIV. Several factors, patient- and not patient-related, may compromise adherence to NIV, such as physical, behavioral, familiar, and social issues. Few data are currently available on the role of psychological factors in influencing NIV adherence.

MATERIALS AND METHODS: In this pilot study, we evaluated the adherence to NIV in a group of 15 adult patients with neuromuscular diseases (Duchenne muscular dystrophy, myotonic dystrophy, and amyotrophic lateral sclerosis) in relation to their grade of depression assessed by the Beck Depression Inventory (BDI) questionnaire. Other data were collected, such as clinical features (age and sex), use of anxiolytic drugs, the presence of a family or professional caregiver, the quality of patient-physician relationship, the beginning of psychological support after BDI screening, and the family acceptance of NIV. NIV adherence was definied as the use of NIV for at least 4 h per night on 70% of nights in a month.

RESULTS: The overall rate of NIV adherence was 60%. Based on the BDI questionnaire, patients who were non-adherent to NIV had a higher rate of depression, mainly observed in the oldest patients. The acceptance of NIV by the family and positive physician-patient interaction seem to favor NIV adherence.

CONCLUSION: Depression can interfere with NIV adherence in patients with neuromuscolar diseases.}, } @article {pmid37762599, year = {2023}, author = {Taneva, SG and Todinova, S and Andreeva, T}, title = {Morphometric and Nanomechanical Screening of Peripheral Blood Cells with Atomic Force Microscopy for Label-Free Assessment of Alzheimer's Disease, Parkinson's Disease, and Amyotrophic Lateral Sclerosis.}, journal = {International journal of molecular sciences}, volume = {24}, number = {18}, pages = {}, pmid = {37762599}, issn = {1422-0067}, support = {KP-06-H31/8//Bulgarian Science Fund/ ; funding programme Open Access Publishing//Baden-Württemberg Ministry of Science, Research and Culture/ ; }, mesh = {Humans ; *Parkinson Disease/diagnosis ; *Amyotrophic Lateral Sclerosis/diagnosis ; *Alzheimer Disease/diagnosis ; Microscopy, Atomic Force ; Blood Cells ; }, abstract = {Neurodegenerative disorders (NDDs) are complex, multifactorial disorders with significant social and economic impact in today's society. NDDs are predicted to become the second-most common cause of death in the next few decades due to an increase in life expectancy but also to a lack of early diagnosis and mainly symptomatic treatment. Despite recent advances in diagnostic and therapeutic methods, there are yet no reliable biomarkers identifying the complex pathways contributing to these pathologies. The development of new approaches for early diagnosis and new therapies, together with the identification of non-invasive and more cost-effective diagnostic biomarkers, is one of the main trends in NDD biomedical research. Here we summarize data on peripheral biomarkers, biofluids (cerebrospinal fluid and blood plasma), and peripheral blood cells (platelets (PLTs) and red blood cells (RBCs)), reported so far for the three most common NDDs-Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). PLTs and RBCs, beyond their primary physiological functions, are increasingly recognized as valuable sources of biomarkers for NDDs. Special attention is given to the morphological and nanomechanical signatures of PLTs and RBCs as biophysical markers for the three pathologies. Modifications of the surface nanostructure and morphometric and nanomechanical signatures of PLTs and RBCs from patients with AD, PD, and ALS have been revealed by atomic force microscopy (AFM). AFM is currently experiencing rapid and widespread adoption in biomedicine and clinical medicine, in particular for early diagnostics of various medical conditions. AFM is a unique instrument without an analog, allowing the generation of three-dimensional cell images with extremely high spatial resolution at near-atomic scale, which are complemented by insights into the mechanical properties of cells and subcellular structures. Data demonstrate that AFM can distinguish between the three pathologies and the normal, healthy state. The specific PLT and RBC signatures can serve as biomarkers in combination with the currently used diagnostic tools. We highlight the strong correlation of the morphological and nanomechanical signatures between RBCs and PLTs in PD, ALS, and AD.}, } @article {pmid37762278, year = {2023}, author = {Mastrangelo, A and Vacchiano, V and Zenesini, C and Ruggeri, E and Baiardi, S and Cherici, A and Avoni, P and Polischi, B and Santoro, F and Capellari, S and Liguori, R and Parchi, P}, title = {Amyloid-Beta Co-Pathology Is a Major Determinant of the Elevated Plasma GFAP Values in Amyotrophic Lateral Sclerosis.}, journal = {International journal of molecular sciences}, volume = {24}, number = {18}, pages = {}, pmid = {37762278}, issn = {1422-0067}, support = {Ricerca Corrente//Ministero della Salute/ ; PE0000006//#NextGenerationEU/ ; }, abstract = {Recent studies reported increased plasma glial acidic fibrillary protein (GFAP) levels in amyotrophic lateral sclerosis (ALS) patients compared to controls. We expanded these findings in a larger cohort, including 156 ALS patients and 48 controls, and investigated the associations of plasma GFAP with clinical variables and other biofluid biomarkers. Plasma GFAP and Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarkers were assessed by the single molecule array and the Lumipulse platforms, respectively. In ALS patients, plasma GFAP was higher than in controls (p < 0.001) and associated with measures of cognitive decline. Twenty ALS patients (12.8%) showed a positive amyloid status (A+), of which nine also exhibited tau pathology (A+T+, namely ALS-AD). ALS-AD patients showed higher plasma GFAP than A- ALS participants (p < 0.001) and controls (p < 0.001), whereas the comparison between A- ALS and controls missed statistical significance (p = 0.07). Plasma GFAP distinguished ALS-AD subjects more accurately (area under the curve (AUC) 0.932 ± 0.027) than plasma p-tau181 (AUC 0.692 ± 0.058, p < 0.0001) and plasma neurofilament light chain protein (AUC, 0.548 ± 0.088, p < 0.0001). Cognitive measures differed between ALS-AD and other ALS patients. AD co-pathology deeply affects plasma GFAP values in ALS patients. Plasma GFAP is an accurate biomarker for identifying AD co-pathology in ALS, which can influence the cognitive phenotype.}, } @article {pmid37762112, year = {2023}, author = {Gimenez, J and Spalloni, A and Cappelli, S and Ciaiola, F and Orlando, V and Buratti, E and Longone, P}, title = {TDP-43 Epigenetic Facets and Their Neurodegenerative Implications.}, journal = {International journal of molecular sciences}, volume = {24}, number = {18}, pages = {}, pmid = {37762112}, issn = {1422-0067}, support = {PathensTDP//Fondazione Italiana di Ricerca per la Sclerosi Laterale Amiotrofica/ ; JPND2020-568-078//EU Joint Programme - Neurodegenerative Disease Research/ ; }, mesh = {Humans ; *Chromatin ; Cytoplasm ; *DNA-Binding Proteins/genetics ; Epigenesis, Genetic ; Epigenomics ; }, abstract = {Since its initial involvement in numerous neurodegenerative pathologies in 2006, either as a principal actor or as a cofactor, new pathologies implicating transactive response (TAR) DNA-binding protein 43 (TDP-43) are regularly emerging also beyond the neuronal system. This reflects the fact that TDP-43 functions are particularly complex and broad in a great variety of human cells. In neurodegenerative diseases, this protein is often pathologically delocalized to the cytoplasm, where it irreversibly aggregates and is subjected to various post-translational modifications such as phosphorylation, polyubiquitination, and cleavage. Until a few years ago, the research emphasis has been focused particularly on the impacts of this aggregation and/or on its widely described role in complex RNA splicing, whether related to loss- or gain-of-function mechanisms. Interestingly, recent studies have strengthened the knowledge of TDP-43 activity at the chromatin level and its implication in the regulation of DNA transcription and stability. These discoveries have highlighted new features regarding its own transcriptional regulation and suggested additional mechanistic and disease models for the effects of TPD-43. In this review, we aim to give a comprehensive view of the potential epigenetic (de)regulations driven by (and driving) this multitask DNA/RNA-binding protein.}, } @article {pmid37762010, year = {2023}, author = {Tsuruta, K and Shidara, T and Miyagishi, H and Nango, H and Nakatani, Y and Suzuki, N and Amano, T and Suzuki, T and Kosuge, Y}, title = {Anti-Inflammatory Effects of Miyako Bidens pilosa in a Mouse Model of Amyotrophic Lateral Sclerosis and Lipopolysaccharide-Stimulated BV-2 Microglia.}, journal = {International journal of molecular sciences}, volume = {24}, number = {18}, pages = {}, pmid = {37762010}, issn = {1422-0067}, support = {22K06654 (Y.K.) and 21K06620 (H.M. and Y.K.)//JSPS KAKENHI/ ; 2211//a Nihon University Research Grant for 2022-2023/ ; 2019//Shorei Foundation for Science and Technology/ ; 2020//The Research Foundation for Pharmaceutical Sciences/ ; }, mesh = {Humans ; Animals ; Mice ; Microglia ; *Amyotrophic Lateral Sclerosis/drug therapy ; *Bidens ; Interleukin-6 ; Lipopolysaccharides/toxicity ; Cytokines ; Disease Models, Animal ; }, abstract = {Neuroinflammation is a fundamental feature in the pathogenesis of amyotrophic lateral sclerosis (ALS) and arises from the activation of astrocytes and microglial cells. Previously, we reported that Miyako Bidens pilosa extract (MBP) inhibited microglial activation and prolonged the life span in a human ALS-linked mutant superoxide dismutase-1 (SOD1[G93A]) transgenic mouse model of ALS (G93A mice). Herein, we evaluated the effect of MBP on microglial activation in the spinal cord of G93A mice and lipopolysaccharide-stimulated BV-2 microglial cells. The administration of MBP inhibited the upregulation of the M1-microglia/macrophage marker (interferon-γ receptor (IFN-γR)) and pro-inflammatory cytokines (tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6) in G93A mice. However, MBP did not affect the increase in the M2-microglia/macrophage marker (IL-13R) and anti-inflammatory cytokines (transforming growth factor (TGF)-β and IL-10) in G93A mice. BV-2 cell exposure to MBP resulted in a decrease in 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium (MTT) reduction activity and bromodeoxyuridine incorporation, without an increase in the number of ethidium homodimer-1-stained dead cells. Moreover, MBP suppressed the production of lipopolysaccharide-induced pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) in BV-2 cells. These results suggest that the selective suppression of M1-related pro-inflammatory cytokines is involved in the therapeutic potential of MBP in ALS model mice.}, } @article {pmid37761265, year = {2023}, author = {Anghel, L and Ciubară, A and Nechita, A and Nechita, L and Manole, C and Baroiu, L and Ciubară, AB and Mușat, CL}, title = {Sleep Disorders Associated with Neurodegenerative Diseases.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {13}, number = {18}, pages = {}, pmid = {37761265}, issn = {2075-4418}, abstract = {Sleep disturbances are common in various neurological pathologies, including amyotrophic lateral sclerosis (ALS), multiple system atrophy (MSA), hereditary ataxias, Huntington's disease (HD), progressive supranuclear palsy (PSP), and dementia with Lewy bodies (DLB). This article reviews the prevalence and characteristics of sleep disorders in these conditions, highlighting their impact on patients' quality of life and disease progression. Sleep-related breathing disorders, insomnia, restless legs syndrome (RLS), periodic limb movement syndrome (PLMS), and rapid eye movement sleep behavior disorder (RBD) are among the common sleep disturbances reported. Both pharmacological and non-pharmacological interventions play crucial roles in managing sleep disturbances and enhancing overall patient care.}, } @article {pmid37760880, year = {2023}, author = {Milella, G and Sciancalepore, D and Cavallaro, G and Piccirilli, G and Nanni, AG and Fraddosio, A and D'Errico, E and Paolicelli, D and Fiorella, ML and Simone, IL}, title = {Acoustic Voice Analysis as a Useful Tool to Discriminate Different ALS Phenotypes.}, journal = {Biomedicines}, volume = {11}, number = {9}, pages = {}, pmid = {37760880}, issn = {2227-9059}, abstract = {Approximately 80-96% of people with amyotrophic lateral sclerosis (ALS) become unable to speak during the disease progression. Assessing upper and lower motor neuron impairment in bulbar regions of ALS patients remains challenging, particularly in distinguishing spastic and flaccid dysarthria. This study aimed to evaluate acoustic voice parameters as useful biomarkers to discriminate ALS clinical phenotypes. Triangular vowel space area (tVSA), alternating motion rates (AMRs), and sequential motion rates (SMRs) were analyzed in 36 ALS patients and 20 sex/age-matched healthy controls (HCs). tVSA, AMR, and SMR values significantly differed between ALS and HCs, and between ALS with prevalent upper (pUMN) and lower motor neuron (pLMN) impairment. tVSA showed higher accuracy in discriminating pUMN from pLMN patients. AMR and SMR were significantly lower in patients with bulbar onset than those with spinal onset, both with and without bulbar symptoms. Furthermore, these values were also lower in patients with spinal onset associated with bulbar symptoms than in those with spinal onset alone. Additionally, AMR and SMR values correlated with the degree of dysphagia. Acoustic voice analysis may be considered a useful prognostic tool to differentiate spastic and flaccid dysarthria and to assess the degree of bulbar involvement in ALS.}, } @article {pmid37760050, year = {2023}, author = {Rubino, V and La Rosa, G and Pipicelli, L and Carriero, F and Damiano, S and Santillo, M and Terrazzano, G and Ruggiero, G and Mondola, P}, title = {Insights on the Multifaceted Roles of Wild-Type and Mutated Superoxide Dismutase 1 in Amyotrophic Lateral Sclerosis Pathogenesis.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {12}, number = {9}, pages = {}, pmid = {37760050}, issn = {2076-3921}, abstract = {Amyotrophic Lateral Sclerosis (ALS) is a progressive motor neurodegenerative disease. Cell damage in ALS is the result of many different, largely unknown, pathogenetic mechanisms. Astrocytes and microglial cells play a critical role also for their ability to enhance a deranged inflammatory response. Excitotoxicity, due to excessive glutamate levels and increased intracellular Ca[2+] concentration, has also been proposed to play a key role in ALS pathogenesis/progression. Reactive Oxygen Species (ROS) behave as key second messengers for multiple receptor/ligand interactions. ROS-dependent regulatory networks are usually mediated by peroxides. Superoxide Dismutase 1 (SOD1) physiologically mediates intracellular peroxide generation. About 10% of ALS subjects show a familial disease associated with different gain-of-function SOD1 mutations. The occurrence of sporadic ALS, not clearly associated with SOD1 defects, has been also described. SOD1-dependent pathways have been involved in neuron functional network as well as in immune-response regulation. Both, neuron depolarization and antigen-dependent T-cell activation mediate SOD1 exocytosis, inducing increased interaction of the enzyme with a complex molecular network involved in the regulation of neuron functional activity and immune response. Here, alteration of SOD1-dependent pathways mediating increased intracellular Ca[2+] levels, altered mitochondria functions and defective inflammatory process regulation have been proposed to be relevant for ALS pathogenesis/progression.}, } @article {pmid37759926, year = {2023}, author = {Shimizu, T and Nakayama, Y and Bokuda, K and Takahashi, K}, title = {Sensory Gating during Voluntary Finger Movement in Amyotrophic Lateral Sclerosis with Sensory Cortex Hyperexcitability.}, journal = {Brain sciences}, volume = {13}, number = {9}, pages = {}, pmid = {37759926}, issn = {2076-3425}, support = {16H05583//Japan Society for the Promotion of Science/ ; 19H03939//Japan Society for the Promotion of Science/ ; 22H03398//Japan Society for the Promotion of Science/ ; }, abstract = {Cortical responses in somatosensory evoked potentials (SEP) are enhanced in patients with amyotrophic lateral sclerosis (ALS). This study investigated whether sensory gating is involved in the pathophysiology of sensory cortical hyperactivity in ALS patients. The median nerve SEP was recorded at rest and during voluntary finger movements in 14 ALS patients and 13 healthy control subjects. The parietal N20, P25, and frontal N30 were analyzed, and sensory gating was assessed by measuring the amplitude of each component during finger movement. The amplitudes of the N20 onset-peak, N20 peak-P25 peak, and N30 onset-peak were higher in ALS patients than in controls. Nonetheless, there were no significant differences in the amplitude reduction ratio of SEPs between patients and controls. There was a significant correlation between the baseline amplitudes of the N20 onset-peak or N20 peak-P25 peak and their gating ratios in patients with ALS. Our findings indicate that the excitability of the primary sensory cortex and secondary motor cortex is enhanced in ALS, while sensory gating is preserved in the early stages of ALS. This result suggests that enhanced SEP is caused by the hyperexcitability of the primary sensory and secondary motor cortices but not by the dysfunction of inhibitory mechanisms during voluntary movements.}, } @article {pmid37759773, year = {2023}, author = {Goto, S and Zhang, Y and Vyas, SA and Zhu, Q and Wildsoet, CF}, title = {Changes in Expression in BMP2 and Two Closely Related Genes in Guinea Pig Retinal Pigment Epithelium during Induction and Recovery from Myopia.}, journal = {Biomolecules}, volume = {13}, number = {9}, pages = {}, pmid = {37759773}, issn = {2218-273X}, support = {R01 EY012392/EY/NEI NIH HHS/United States ; }, mesh = {Animals ; Guinea Pigs ; Bone Morphogenetic Protein 2/genetics ; Choroid ; *Myopia/genetics ; *Retinal Pigment Epithelium ; }, abstract = {PURPOSE: We previously reported differential gene expression of the bone morphogenetic protein 2 (Bmp2) in guinea pig retinal pigment epithelium (RPE) after 1 day of hyperopic defocus, imposed with a negative contact lens (CLs). The study reported here sought to obtain insights into the temporal profiles of gene expression changes in Bmp2, as well as those of two closely related genes, the inhibitor of DNA binding 3 (Id3) and Noggin (Nog), both during myopia induction and when the CL treatment was terminated to allow recovery from induced myopia.

METHODS: To induce myopia, 2-week-old pigmented guinea pigs (New Zealand strain, n = 8) wore monocular -10 diopter (D) rigid gas-permeable (RGP) CLs for one week, while the other eye served as a control. Ocular measurements were made at baseline, 3 days, and 7 days after the initiation of CL wear, with treatment then being terminated and additional measurements being made after a further 3 days, 1 week, and 2 weeks. Spherical equivalent refractive errors (SERs), axial length (AL), choroidal thickness (ChT), and scleral thickness (ScT) data were collected using retinoscopy, optical biometry (Lenstar), and spectral domain optical coherence tomography (SD-OCT), respectively. RPE samples were collected from both eyes of the guinea pigs after either 1 day or 1 week of CL wear or 1 day or 2 weeks after its termination, and RNA was subsequently isolated and subjected to quantitative real-time PCR (qRT-PCR) analyses, targeting the Bmp2, Id3, and Nog genes.

RESULTS: Mean interocular differences (treated-control) in AL and SER were significantly different from baseline after 3 and 7 days of CL wear, consistent with induced myopia (p < 0.001 for all cases). Termination of CL wear resulted in the normalization (i.e., recovery) of the ALs and SERs of the treated eyes within 7 days, and the earlier significant ChT thinning with CL wear (p = 0004, day 7) was replaced by rapid thickening, which remained significant on day 7 (p = 0.009) but had normalized by day 14. The ChT changes were much smaller in magnitude than the AL changes in both phases. Interocular differences in the ScT showed no significant changes. The Bmp2 and Id3 genes were both significantly downregulated with CL wear, after 1 day (p = 0.012 and 0.016) and 7 days (p = 0.002 and 0.005), while Bmp2 gene expression increased and Nog gene expression decreased after the termination of CL wear, albeit transiently, which was significant on 1 day (p = 0.004 and 0.04) but not 2 weeks later. No change in Id3 gene expression was observed over the latter period. Conclusions: The above patterns of myopia induction and recovery validate this negative RGP-CL model as an alternative to traditional spectacle lens models for guinea pigs. The defocus-driven, sign-dependent changes in the expression of the Bmp2 gene in guinea pig RPE are consistent with observations in chicks and demonstrate the important role of BMP2 in eye growth regulation.}, } @article {pmid37759656, year = {2023}, author = {Angelopoulou, E and Pyrgelis, ES and Ahire, C and Suman, P and Mishra, A and Piperi, C}, title = {Functional Implications of Protein Arginine Methyltransferases (PRMTs) in Neurodegenerative Diseases.}, journal = {Biology}, volume = {12}, number = {9}, pages = {}, pmid = {37759656}, issn = {2079-7737}, abstract = {During the aging of the global population, the prevalence of neurodegenerative diseases will be continuously growing. Although each disorder is characterized by disease-specific protein accumulations, several common pathophysiological mechanisms encompassing both genetic and environmental factors have been detected. Among them, protein arginine methyltransferases (PRMTs), which catalyze the methylation of arginine of various substrates, have been revealed to regulate several cellular mechanisms, including neuronal cell survival and excitability, axonal transport, synaptic maturation, and myelination. Emerging evidence highlights their critical involvement in the pathophysiology of neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), frontotemporal dementia-amyotrophic lateral sclerosis (FTD-ALS) spectrum, Huntington's disease (HD), spinal muscular atrophy (SMA) and spinal and bulbar muscular atrophy (SBMA). Underlying mechanisms include the regulation of gene transcription and RNA splicing, as well as their implication in various signaling pathways related to oxidative stress responses, apoptosis, neuroinflammation, vacuole degeneration, abnormal protein accumulation and neurotransmission. The targeting of PRMTs is a therapeutic approach initially developed against various forms of cancer but currently presents a novel potential strategy for neurodegenerative diseases. In this review, we discuss the accumulating evidence on the role of PRMTs in the pathophysiology of neurodegenerative diseases, enlightening their pathogenesis and stimulating future research.}, } @article {pmid37759591, year = {2023}, author = {Wang, X and Hu, W and Li, Y and Jiang, M and Zhao, N and Cao, H and Liao, M}, title = {Cytochrome P450s-Involved Enhanced Metabolism Contributes to the High Level of Nicosulfuron Resistance in Digitaria sanguinalis from China.}, journal = {Biology}, volume = {12}, number = {9}, pages = {}, pmid = {37759591}, issn = {2079-7737}, support = {202203a06020016//the Science and Technology Major Project of Anhui Province/ ; rc342004//the Talent Research Project of Anhui Agricultural University/ ; X202310364519//the College Students' Innovation Training Project in Anhui Agricultural University/ ; }, abstract = {Large crabgrass (Digitaria sanguinalis (L.) Scop.) is one of the major malignant grass weeds in Chinese maize (Zea mays L.) fields, and it has recently developed resistance to the acetolactate synthase (ALS)-inhibiting herbicide nicosulfuron. This study focused on a suspected nicosulfuron-resistant (R) population (LJ-01) of D. sanguinalis, collected from Lujiang County in Anhui Province, China, to explore the resistance level and potential resistance mechanism. Whole-plant dose-response testing confirmed that the LJ-01 population evolved a high level of resistance to nicosulfuron (11.5-fold) compared to the susceptible (S) population, DY-02. The ALS gene sequencing and relative expression assay of the R plants indicated that target gene mutation and overexpression were not responsible for the resistance phenotype. However, pretreatment with malathion, a known cytochrome P450 monooxygenase (P450) inhibitor, alleviated the resistance of the R population to nicosulfuron by approximately 36%. High-performance liquid chromatography (HPLC) analysis revealed that the R plants metabolized nicosulfuron faster than the S plants. Moreover, cross-resistance testing suggested that the R population exhibited low levels of resistance to thifensulfuron-methyl and pyrazosulfuron-ethyl, but it remained susceptible to rimsulfuron. Multiple resistance patterns showed that the R population evolved low resistance to the photosystem inhibitors bromoxynil octanoate and atrazine and sensitivity to the acetyl-CoA carboxylase (ACCase) inhibitor cyhalofop-butyl and the 4-hydroxyphenylpyruvate dioxygenase (HPPD) inhibitors tembotrione, mesotrione, and topramezone. This study reports, for the first time, the simultaneous resistance to ALS and different photosystem inhibitors in D. sanguinalis. The nicosulfuron resistance observed in the R population could primarily be attributed to an enhanced metabolism involving P450 enzymes.}, } @article {pmid37759540, year = {2023}, author = {Sanghai, N and Tranmer, GK}, title = {Biochemical and Molecular Pathways in Neurodegenerative Diseases: An Integrated View.}, journal = {Cells}, volume = {12}, number = {18}, pages = {}, pmid = {37759540}, issn = {2073-4409}, abstract = {Neurodegenerative diseases (NDDs) like Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS) are defined by a myriad of complex aetiologies. Understanding the common biochemical molecular pathologies among NDDs gives an opportunity to decipher the overlapping and numerous cross-talk mechanisms of neurodegeneration. Numerous interrelated pathways lead to the progression of neurodegeneration. We present evidence from the past pieces of literature for the most usual global convergent hallmarks like ageing, oxidative stress, excitotoxicity-induced calcium butterfly effect, defective proteostasis including chaperones, autophagy, mitophagy, and proteosome networks, and neuroinflammation. Herein, we applied a holistic approach to identify and represent the shared mechanism across NDDs. Further, we believe that this approach could be helpful in identifying key modulators across NDDs, with a particular focus on AD, PD, and ALS. Moreover, these concepts could be applied to the development and diagnosis of novel strategies for diverse NDDs.}, } @article {pmid37759469, year = {2023}, author = {Castillo Bautista, CM and Eismann, K and Gentzel, M and Pelucchi, S and Mertens, J and Walters, HE and Yun, MH and Sterneckert, J}, title = {Obatoclax Rescues FUS-ALS Phenotypes in iPSC-Derived Neurons by Inducing Autophagy.}, journal = {Cells}, volume = {12}, number = {18}, pages = {}, pmid = {37759469}, issn = {2073-4409}, support = {R01 AG056306/AG/NIA NIH HHS/United States ; P30 AG062429/AG/NIA NIH HHS/United States ; ERC-STG-2019-852086/ERC_/European Research Council/International ; AG056306/AG/NIA NIH HHS/United States ; RF1 AG056306/AG/NIA NIH HHS/United States ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism ; Motor Neurons/metabolism ; *Induced Pluripotent Stem Cells/metabolism ; Mutation ; Autophagy/physiology ; Phenotype ; Proto-Oncogene Proteins c-bcl-2/metabolism ; RNA-Binding Protein FUS/genetics/metabolism ; }, abstract = {Aging is associated with the disruption of protein homeostasis and causally contributes to multiple diseases, including amyotrophic lateral sclerosis (ALS). One strategy for restoring protein homeostasis and protecting neurons against age-dependent diseases such as ALS is to de-repress autophagy. BECN1 is a master regulator of autophagy; however, is repressed by BCL2 via a BH3 domain-mediated interaction. We used an induced pluripotent stem cell model of ALS caused by mutant FUS to identify a small molecule BH3 mimetic that disrupts the BECN1-BCL2 interaction. We identified obatoclax as a brain-penetrant drug candidate that rescued neurons at nanomolar concentrations by reducing cytoplasmic FUS levels, restoring protein homeostasis, and reducing degeneration. Proteomics data suggest that obatoclax protects neurons via multiple mechanisms. Thus, obatoclax is a candidate for repurposing as a possible ALS therapeutic and, potentially, for other age-associated disorders linked to defects in protein homeostasis.}, } @article {pmid37759179, year = {2023}, author = {Garcia-Vaquero, ML and Heim, M and Flix, B and Pereira, M and Palin, L and Marques, TM and Pinto, FR and de Las Rivas, J and Voigt, A and Besse, F and Gama-Carvalho, M}, title = {Analysis of asymptomatic Drosophila models for ALS and SMA reveals convergent impact on functional protein complexes linked to neuro-muscular degeneration.}, journal = {BMC genomics}, volume = {24}, number = {1}, pages = {576}, pmid = {37759179}, issn = {1471-2164}, mesh = {Adult ; Humans ; Animals ; *Amyotrophic Lateral Sclerosis/genetics ; Drosophila/genetics ; *Muscular Atrophy, Spinal ; Motor Neurons ; RNA ; DNA-Binding Proteins ; *Drosophila Proteins/genetics ; }, abstract = {BACKGROUND: Spinal Muscular Atrophy (SMA) and Amyotrophic Lateral Sclerosis (ALS) share phenotypic and molecular commonalities, including the fact that they can be caused by mutations in ubiquitous proteins involved in RNA metabolism, namely SMN, TDP-43 and FUS. Although this suggests the existence of common disease mechanisms, there is currently no model to explain the resulting motor neuron dysfunction. In this work we generated a parallel set of Drosophila models for adult-onset RNAi and tagged neuronal expression of the fly orthologues of the three human proteins, named Smn, TBPH and Caz, respectively. We profiled nuclear and cytoplasmic bound mRNAs using a RIP-seq approach and characterized the transcriptome of the RNAi models by RNA-seq. To unravel the mechanisms underlying the common functional impact of these proteins on neuronal cells, we devised a computational approach based on the construction of a tissue-specific library of protein functional modules, selected by an overall impact score measuring the estimated extent of perturbation caused by each gene knockdown.

RESULTS: Transcriptome analysis revealed that the three proteins do not bind to the same RNA molecules and that only a limited set of functionally unrelated transcripts is commonly affected by their knock-down. However, through our integrative approach we were able to identify a concerted effect on protein functional modules, albeit acting through distinct targets. Most strikingly, functional annotation revealed that these modules are involved in critical cellular pathways for motor neurons, including neuromuscular junction function. Furthermore, selected modules were found to be significantly enriched in orthologues of human neuronal disease genes.

CONCLUSIONS: The results presented here show that SMA and ALS disease-associated genes linked to RNA metabolism functionally converge on neuronal protein complexes, providing a new hypothesis to explain the common motor neuron phenotype. The functional modules identified represent promising biomarkers and therapeutic targets, namely given their alteration in asymptomatic settings.}, } @article {pmid37759084, year = {2024}, author = {Tan, EL and Tahedl, M and Lope, J and Hengeveld, JC and Doherty, MA and McLaughlin, RL and Hardiman, O and Chang, KM and Finegan, E and Bede, P}, title = {Language deficits in primary lateral sclerosis: cortical atrophy, white matter degeneration and functional disconnection between cerebral regions.}, journal = {Journal of neurology}, volume = {271}, number = {1}, pages = {431-445}, pmid = {37759084}, issn = {1432-1459}, mesh = {Humans ; *White Matter/diagnostic imaging/pathology ; Diffusion Tensor Imaging/methods ; Prospective Studies ; *Motor Neuron Disease/pathology ; Atrophy/pathology ; Magnetic Resonance Imaging ; }, abstract = {BACKGROUND: Primary lateral sclerosis (PLS) is traditionally regarded as a pure upper motor neuron disorder, but recent cases series have highlighted cognitive deficits in executive and language domains.

METHODS: A single-centre, prospective neuroimaging study was conducted with comprehensive clinical and genetic profiling. The structural and functional integrity of language-associated brain regions and networks were systematically evaluated in 40 patients with PLS in comparison to 111 healthy controls. The structural integrity of the arcuate fascicle, frontal aslant tract, inferior occipito-frontal fascicle, inferior longitudinal fascicle, superior longitudinal fascicle and uncinate fascicle was evaluated. Functional connectivity between the supplementary motor region and the inferior frontal gyrus and connectivity between Wernicke's and Broca's areas was also assessed.

RESULTS: Cortical thickness reductions were observed in both Wernicke's and Broca's areas. Fractional anisotropy reduction was noted in the aslant tract and increased radical diffusivity (RD) identified in the aslant tract, arcuate fascicle and superior longitudinal fascicle in the left hemisphere. Functional connectivity was reduced along the aslant track, i.e. between the supplementary motor region and the inferior frontal gyrus, but unaffected between Wernicke's and Broca's areas. Cortical thickness alterations, structural and functional connectivity changes were also noted in the right hemisphere.

CONCLUSIONS: Disease-burden in PLS is not confined to motor regions, but there is also a marked involvement of language-associated tracts, networks and cortical regions. Given the considerably longer survival in PLS compared to ALS, the impact of language impairment on the management of PLS needs to be carefully considered.}, } @article {pmid37758732, year = {2023}, author = {Marzullo, M and Romano, G and Pellacani, C and Riccardi, F and Ciapponi, L and Feiguin, F}, title = {Su(var)3-9 mediates age-dependent increase in H3K9 methylation on TDP-43 promoter triggering neurodegeneration.}, journal = {Cell death discovery}, volume = {9}, number = {1}, pages = {357}, pmid = {37758732}, issn = {2058-7716}, abstract = {Aging progressively modifies the physiological balance of the organism increasing susceptibility to both genetic and sporadic neurodegenerative diseases. These changes include epigenetic chromatin remodeling events that may modify the transcription levels of disease-causing genes affecting neuronal survival. However, how these events interconnect is not well understood. Here, we found that Su(var)3-9 causes increased methylation of histone H3K9 in the promoter region of TDP-43, the most frequently altered factor in amyotrophic lateral sclerosis (ALS), affecting the mRNA and protein expression levels of this gene through epigenetic modifications that appear to be conserved in aged Drosophila brains, mouse, and human cells. Remarkably, augmented Su(var)3-9 activity causes a decrease in TDP-43 expression followed by early defects in locomotor activities. In contrast, decreasing Su(var)3-9 action promotes higher levels of TDP-43 expression, improving motility parameters in old flies. The data uncover a novel role of this enzyme in regulating TDP-43 expression and locomotor senescence and indicate conserved epigenetic mechanisms that may play a role in the pathogenesis of ALS.}, } @article {pmid37758454, year = {2024}, author = {Goutman, SA and Boss, J and Jang, DG and Mukherjee, B and Richardson, RJ and Batterman, S and Feldman, EL}, title = {Environmental risk scores of persistent organic pollutants associate with higher ALS risk and shorter survival in a new Michigan case/control cohort.}, journal = {Journal of neurology, neurosurgery, and psychiatry}, volume = {95}, number = {3}, pages = {241-248}, pmid = {37758454}, issn = {1468-330X}, support = {K23 ES027221/ES/NIEHS NIH HHS/United States ; R01 ES030049/ES/NIEHS NIH HHS/United States ; UL1 TR002240/TR/NCATS NIH HHS/United States ; R01 NS127188/NS/NINDS NIH HHS/United States ; R01 TS000289/TS/ATSDR CDC HHS/United States ; R01TS000289/ACL/ACL HHS/United States ; }, mesh = {Humans ; Persistent Organic Pollutants ; Michigan/epidemiology ; *Amyotrophic Lateral Sclerosis ; *Environmental Pollutants/adverse effects ; Risk Factors ; *Hydrocarbons, Chlorinated ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a fatal, progressive neurogenerative disease caused by combined genetic susceptibilities and environmental exposures. Identifying and validating these exposures are of paramount importance to modify disease risk. We previously reported that persistent organic pollutants (POPs) associate with ALS risk and survival and aimed to replicate these findings in a new cohort.

METHOD: Participants with and without ALS recruited in Michigan provided plasma samples for POPs analysis by isotope dilution with triple quadrupole mass spectrometry. ORs for risk models and hazard ratios for survival models were calculated for individual POPs. POP mixtures were represented by environmental risk scores (ERS), a summation of total exposures, to evaluate the association with risk (ERS[risk]) and survival (ERS[survival]).

RESULTS: Samples from 164 ALS and 105 control participants were analysed. Several individual POPs significantly associated with ALS, including 8 of 22 polychlorinated biphenyls and 7 of 10 organochlorine pesticides (OCPs). ALS risk was most strongly represented by the mixture effects of OCPs alpha-hexachlorocyclohexane, hexachlorobenzene, trans-nonachlor and cis-nonachlor and an interquartile increase in ERS[risk] enhanced ALS risk 2.58 times (p<0.001). ALS survival was represented by the combined mixture of all POPs and an interquartile increase in ERS[survival] enhanced ALS mortality rate 1.65 times (p=0.008).

CONCLUSIONS: These data continue to support POPs as important factors for ALS risk and progression and replicate findings in a new cohort. The assessments of POPs in non-Michigan ALS cohorts are encouraged to better understand the global effect and the need for targeted disease risk reduction strategies.}, } @article {pmid37758263, year = {2024}, author = {Crumbley, C and Cepni, AB and Taylor, A and Thompson, D and Moran, NE and Olvera, N and O'Connor, DP and Johnston, CA and Ledoux, TA}, title = {Exploring Factors Associated With Accelerometer Validity Among Ethnically Diverse Toddlers.}, journal = {Pediatric exercise science}, volume = {36}, number = {2}, pages = {66-74}, doi = {10.1123/pes.2022-0114}, pmid = {37758263}, issn = {1543-2920}, mesh = {Humans ; Male ; Female ; Child, Preschool ; Adult ; *Exercise ; *Sedentary Behavior ; Parents ; Patient Compliance ; Accelerometry ; }, abstract = {PURPOSE: Studying physical activity in toddlers using accelerometers is challenging due to noncompliance with wear time (WT) and activity log (AL) instructions. The aims of this study are to examine relationships between WT and AL completion and (1) demographic and socioeconomic variables, (2) parenting style, and (3) whether sedentary time differs by AL completion.

METHODS: Secondary analysis was performed using baseline data from a community wellness program randomized controlled trial for parents with toddlers (12-35 mo). Parents had toddlers wear ActiGraph wGT3x accelerometers and completed ALs. Valid days included ≥600-minute WT. Analysis of variance and chi-square analyses were used.

RESULTS: The sample (n = 50) comprised racial and ethnically diverse toddlers (mean age = 27 mo, 58% male) and parents (mean age = 31.7 y, 84% female). Twenty-eight families (56%) returned valid accelerometer data with ALs. Participants in relationships were more likely to complete ALs (P < .05). Toddler sedentary time did not differ between those with ALs and those without.

CONCLUSIONS: We found varied compliance with WT instructions and AL completion. Returned AL quality was poor, presenting challenges in correctly characterizing low-activity counts to improve internal validity of WT and physical activity measures. Support from marital partners may be important for adherence to study protocols.}, } @article {pmid37756636, year = {2023}, author = {Wang, Y and Liu, L and Chen, H and Yang, Y and Mu, C and Ren, H and Liu, Y and Yu, L and Fang, Q and Wang, G and Hao, Z}, title = {Disrupted phase behavior of FUS underlies poly-PR-induced DNA damage in amyotrophic lateral sclerosis.}, journal = {Human molecular genetics}, volume = {33}, number = {1}, pages = {64-77}, doi = {10.1093/hmg/ddad163}, pmid = {37756636}, issn = {1460-2083}, support = {//National Natural Science Foundation of China/ ; //Priority Academic Program Development of Jiangsu Higher Education Institutions/ ; 2020M671572//China Postdoctoral Science Foundation/ ; 21KJA180003//Key Project of Natural Science Foundation of Jiangsu Provincial Higher Education Institutions/ ; 32271039//National Natural Science Foundation of China/ ; }, mesh = {Animals ; Mice ; *Amyotrophic Lateral Sclerosis/genetics/metabolism ; DNA Repeat Expansion ; *Frontotemporal Dementia/genetics/metabolism ; Proteins/genetics ; DNA Damage/genetics ; Arginine/genetics ; C9orf72 Protein/genetics/metabolism ; Dipeptides/genetics ; }, abstract = {GGGGCC (G4C2) hexanucleotide repeat expansion (HRE) in the first intron of the chromosome 9 open reading frame 72 (C9ORF72) gene is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Among the five dipeptide repeat proteins translated from G4C2 HRE, arginine-rich poly-PR (proline:arginine) is extremely toxic. However, the molecular mechanism responsible for poly-PR-induced cell toxicity remains incompletely understood. Here, we found that poly-PR overexpression triggers severe DNA damage in cultured cells, primary cortical neurons, and the motor cortex of a poly-PR transgenic mouse model. Interestingly, we identified a linkage between poly-PR and RNA-binding protein fused in sarcoma (FUS), another ALS-related gene product associated with DNA repair. Poly-PR interacts with FUS both in vitro and in vivo, phase separates with FUS in a poly-PR concentration-dependent manner, and impairs the fluidity of FUS droplets in vitro and in cells. Moreover, poly-PR impedes the recruitment of FUS and its downstream protein XRCC1 to DNA damage foci after microirradiation. Importantly, overexpression of FUS significantly decreased the level of DNA damage and dramatically reduced poly-PR-induced cell death. Our data suggest the severe DNA damage caused by poly-PR and highlight the interconnection between poly-PR and FUS, enlightening the potential therapeutic role of FUS in alleviating poly-PR-induced cell toxicity.}, } @article {pmid37756598, year = {2023}, author = {Prior-González, M and Lazo-Gómez, R and Tapia, R}, title = {Sodium butyrate does not protect spinal motor neurons from AMPA-induced excitotoxic degeneration in vivo.}, journal = {Disease models & mechanisms}, volume = {16}, number = {10}, pages = {}, pmid = {37756598}, issn = {1754-8411}, mesh = {Humans ; Animals ; *Amyotrophic Lateral Sclerosis/pathology ; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid/metabolism ; Butyric Acid/pharmacology/metabolism ; Motor Neurons/pathology ; Spinal Cord/pathology ; }, abstract = {Motor neuron (MN) loss is the primary pathological hallmark of amyotrophic lateral sclerosis (ALS). Histone deacetylase 4 (HDAC4) is one of several factors involved in nerve-muscle communication during MN loss, hindering muscle reinnervation, as shown in humans and in animal models of ALS, and may explain the differential progression observed in patients with ALS - rapid versus slow progression. In this work, we inhibited HDAC4 activity through the administration of a pan-histone deacetylase inhibitor, sodium butyrate, in an in vivo model of chronic spinal MN death induced by AMPA-mediated excitotoxicity. We infused AMPA into the spinal cord at low and high doses, which mimic the rapid and slow progression observed in humans, respectively. We found that muscle HDAC4 expression was increased by high-dose infusion of AMPA. Treatment of animals with sodium butyrate further decreased expression of muscle HDAC4, although non-significantly, and did not prevent the paralysis or the MN loss induced by AMPA infusion. These results inform on the role of muscle HDAC4 in MN degeneration in vivo and provide insights for the search for more suitable therapeutic strategies.}, } @article {pmid37755677, year = {2024}, author = {Hu, C and Yan, Y and Jin, Y and Yang, J and Xi, Y and Zhong, Z}, title = {Decoding the Cellular Trafficking of Prion-like Proteins in Neurodegenerative Diseases.}, journal = {Neuroscience bulletin}, volume = {40}, number = {2}, pages = {241-254}, pmid = {37755677}, issn = {1995-8218}, mesh = {Humans ; *Prions ; *Neurodegenerative Diseases/pathology ; Amyloid beta-Peptides ; *Alzheimer Disease ; alpha-Synuclein ; tau Proteins ; *Parkinson Disease ; }, abstract = {The accumulation and spread of prion-like proteins is a key feature of neurodegenerative diseases (NDs) such as Alzheimer's disease, Parkinson's disease, or Amyotrophic Lateral Sclerosis. In a process known as 'seeding', prion-like proteins such as amyloid beta, microtubule-associated protein tau, α-synuclein, silence superoxide dismutase 1, or transactive response DNA-binding protein 43 kDa, propagate their misfolded conformations by transforming their respective soluble monomers into fibrils. Cellular and molecular evidence of prion-like propagation in NDs, the clinical relevance of their 'seeding' capacities, and their levels of contribution towards disease progression have been intensively studied over recent years. This review unpacks the cyclic prion-like propagation in cells including factors of aggregate internalization, endo-lysosomal leaking, aggregate degradation, and secretion. Debates on the importance of the role of prion-like protein aggregates in NDs, whether causal or consequent, are also discussed. Applications lead to a greater understanding of ND pathogenesis and increased potential for therapeutic strategies.}, } @article {pmid37753578, year = {2023}, author = {Yang, X and Hayes, LR}, title = {Order from chaos: Using CSF proteomics to predict ALS progression.}, journal = {Annals of clinical and translational neurology}, volume = {10}, number = {12}, pages = {2176-2178}, pmid = {37753578}, issn = {2328-9503}, support = {R03 NS127011/NS/NINDS NIH HHS/United States ; R01 NS123538/NS/NINDS NIH HHS/United States ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/cerebrospinal fluid/diagnosis ; Biomarkers ; Disease Progression ; *Proteomics ; *Cerebrospinal Fluid Proteins/analysis ; }, } @article {pmid37753280, year = {2023}, author = {Orr, JE and Chen, K and Vaida, F and Schmickl, CN and Laverty, CG and Ravits, J and Lesser, D and Bhattacharjee, R and Malhotra, A and Owens, RL}, title = {Effectiveness of long-term noninvasive ventilation measured by remote monitoring in neuromuscular disease.}, journal = {ERJ open research}, volume = {9}, number = {5}, pages = {}, pmid = {37753280}, issn = {2312-0541}, support = {K23 HL151880/HL/NHLBI NIH HHS/United States ; K23 HL161336/HL/NHLBI NIH HHS/United States ; }, abstract = {BACKGROUND AND OBJECTIVE: Patients with neuromuscular disease are often treated with home noninvasive ventilation (NIV) with devices capable of remote patient monitoring. We sought to determine whether long-term NIV data could provide insight into the effectiveness of ventilation over time.

METHODS: We abstracted available longitudinal data for adults with neuromuscular disease in monthly increments from first available to most recent. Generalised linear mixed-effects modelling with subject-level random effects was used to evaluate trajectories over time.

RESULTS: 1799 months of data across 85 individuals (median age 61, interquartile range (IQR) 46-71 years; 44% female; 49% amyotrophic lateral sclerosis (ALS)) were analysed, with a median (IQR) of 17 (8-35) months per individual. Over time, tidal volume increased and respiratory rate decreased. Dynamic respiratory system compliance decreased, accompanied by increased pressure support. Compared to volume-assured mode, fixed-pressure modes were associated with lower initial tidal volume, higher respiratory rate and lower pressures, which did not fully equalise with volume-assured mode over time. Compared with non-ALS patients, those with ALS had lower initial pressure support, but faster increases in pressure support over time, and ALS was associated wtih a more robust increase in respiratory rate in response to low tidal volume. Nonsurvivors did not differ from survivors in ventilatory trajectories over time, but did exhibit decreasing NIV use prior to death, in contrast with stable use in survivors.

CONCLUSION: NIV keeps breathing patterns stable over time, but support needs are dynamic and influenced by diagnosis and ventilation mode. Mortality is preceded by decreased NIV use rather than inadequate support during use.}, } @article {pmid37753182, year = {2023}, author = {Marciante, AB and Seven, YB and Kelly, MN and Perim, RR and Mitchell, GS}, title = {Magnitude and Mechanism of Phrenic Long-term Facilitation Shift Between Daily Rest Versus Active Phase.}, journal = {Function (Oxford, England)}, volume = {4}, number = {6}, pages = {zqad041}, pmid = {37753182}, issn = {2633-8823}, support = {T32 HL134621/HL/NHLBI NIH HHS/United States ; }, mesh = {Rats ; Animals ; Humans ; Rats, Sprague-Dawley ; *Serotonin ; *Hypoxia ; Signal Transduction ; Adenosine ; }, abstract = {Plasticity is a fundamental property of the neural system controlling breathing. One key example of respiratory motor plasticity is phrenic long-term facilitation (pLTF), a persistent increase in phrenic nerve activity elicited by acute intermittent hypoxia (AIH). pLTF can arise from distinct cell signaling cascades initiated by serotonin versus adenosine receptor activation, respectively, and interact via powerful cross-talk inhibition. Here, we demonstrate that the daily rest/active phase and the duration of hypoxic episodes within an AIH protocol have profound impact on the magnitude and mechanism of pLTF due to shifts in serotonin/adenosine balance. Using the historical "standard" AIH protocol (3, 5-min moderate hypoxic episodes), we demonstrate that pLTF magnitude is unaffected by exposure in the midactive versus midrest phase, yet the mechanism driving pLTF shifts from serotonin-dominant (midrest) to adenosine-dominant (midactive). This mechanistic "flip" results from combined influences of hypoxia-evoked adenosine release and daily fluctuations in basal spinal adenosine. Since AIH evokes less adenosine with shorter (15, 1-min) hypoxic episodes, midrest pLTF is amplified due to diminished adenosine constraint on serotonin-driven plasticity; in contrast, elevated background adenosine during the midactive phase suppresses serotonin-dominant pLTF. These findings demonstrate the importance of the serotonin/adenosine balance in regulating the amplitude and mechanism of AIH-induced pLTF. Since AIH is emerging as a promising therapeutic modality to restore respiratory and nonrespiratory movements in people with spinal cord injury or ALS, knowledge of how time-of-day and hypoxic episode duration impact the serotonin/adenosine balance and the magnitude and mechanism of pLTF has profound biological, experimental, and translational implications.}, } @article {pmid37752364, year = {2023}, author = {Guan, T and Zhou, T and Zhang, X and Guo, Y and Yang, C and Lin, J and Zhang, JV and Cheng, Y and Marzban, H and Wang, YT and Kong, J}, title = {Selective removal of misfolded SOD1 delays disease onset in a mouse model of amyotrophic lateral sclerosis.}, journal = {Cellular and molecular life sciences : CMLS}, volume = {80}, number = {10}, pages = {304}, pmid = {37752364}, issn = {1420-9071}, mesh = {Humans ; Animals ; Mice ; *Amyotrophic Lateral Sclerosis/genetics ; Superoxide Dismutase-1/genetics ; *Neurodegenerative Diseases ; Disease Models, Animal ; Motor Neurons ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease. There is no cure currently. The discovery that mutations in the gene SOD1 are a cause of ALS marks a breakthrough in the search for effective treatments for ALS. SOD1 is an antioxidant that is highly expressed in motor neurons. Human SOD1 is prone to aberrant modifications. Familial ALS-linked SOD1 variants are particularly susceptible to aberrant modifications. Once modified, SOD1 undergoes conformational changes and becomes misfolded. This study aims to determine the effect of selective removal of misfolded SOD1 on the pathogenesis of ALS.

METHODS: Based on the chaperone-mediated protein degradation pathway, we designed a fusion peptide named CT4 and tested its efficiency in knocking down intracellularly misfolded SOD1 and its efficacy in modifying the pathogenesis of ALS.

RESULTS: Expression of the plasmid carrying the CT4 sequence in human HEK cells resulted in robust removal of misfolded SOD1 induced by serum deprivation. Co-transfection of the CT4 and the G93A-hSOD1 plasmids at various ratios demonstrated a dose-dependent knockdown efficiency on G93A-hSOD1, which could be further increased when misfolding of SOD1 was enhanced by serum deprivation. Application of the full-length CT4 peptide to primary cultures of neurons expressing the G93A variant of human SOD1 revealed a time course of the degradation of misfolded SOD1; misfolded SOD1 started to decrease by 2 h after the application of CT4 and disappeared by 7 h. Intravenous administration of the CT4 peptide at 10 mg/kg to the G93A-hSOD1 reduced human SOD1 in spinal cord tissue by 68% in 24 h and 54% in 48 h in presymptomatic ALS mice. Intraperitoneal administration of the CT4 peptide starting from 60 days of age significantly delayed the onset of ALS and prolonged the lifespan of the G93A-hSOD1 mice.

CONCLUSIONS: The CT4 peptide directs the degradation of misfolded SOD1 in high efficiency and specificity. Selective removal of misfolded SOD1 significantly delays the onset of ALS, demonstrating that misfolded SOD1 is the toxic form of SOD1 that causes motor neuron death. The study proves that selective removal of misfolded SOD1 is a promising treatment for ALS.}, } @article {pmid37752346, year = {2024}, author = {Cabrera, GT and Meijboom, KE and Abdallah, A and Tran, H and Foster, Z and Weiss, A and Wightman, N and Stock, R and Gendron, T and Gruntman, A and Giampetruzzi, A and Petrucelli, L and Brown, RH and Mueller, C}, title = {Artificial microRNA suppresses C9ORF72 variants and decreases toxic dipeptide repeat proteins in vivo.}, journal = {Gene therapy}, volume = {31}, number = {3-4}, pages = {105-118}, pmid = {37752346}, issn = {1476-5462}, support = {NS088689//U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; R01 NS088689/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Humans ; Mice ; *Amyotrophic Lateral Sclerosis/genetics/therapy ; C9orf72 Protein/genetics/metabolism ; Dipeptides/genetics/metabolism ; DNA Repeat Expansion/genetics ; Mice, Transgenic ; *MicroRNAs/genetics ; *Neurodegenerative Diseases ; Proteins/genetics/metabolism ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that affects motor neurons, causing progressive muscle weakness and respiratory failure. The presence of an expanded hexanucleotide repeat in chromosome 9 open reading frame 72 (C9ORF72) is the most frequent mutation causing familial ALS and frontotemporal dementia (FTD). To determine if suppressing expression of C9ORF72 gene products can reduce toxicity, we designed a set of artificial microRNAs (amiRNA) targeting the human C9ORF72 gene. Here we report that an AAV9-mediated amiRNA significantly suppresses expression of the C9ORF72 mRNA, protein, and toxic dipeptide repeat proteins generated by the expanded repeat in the brain and spinal cord of C9ORF72 transgenic mice.}, } @article {pmid37752099, year = {2024}, author = {Koreki, A and Michel, S and Lebeaux, C and Trouilh, L and Délye, C}, title = {Prevalence, spatial structure and evolution of resistance to acetolactate-synthase (ALS) inhibitors and 2,4-D in the major weed Papaver rhoeas (L.) assessed using a massive, country-wide sampling.}, journal = {Pest management science}, volume = {80}, number = {2}, pages = {637-647}, doi = {10.1002/ps.7791}, pmid = {37752099}, issn = {1526-4998}, support = {//Corteva Agriscience/ ; }, mesh = {2,4-Dichlorophenoxyacetic Acid/pharmacology ; *Acetolactate Synthase/antagonists & inhibitors/genetics ; Herbicide Resistance/genetics ; *Herbicides/pharmacology ; Lactates ; Mutation ; Nucleotides ; *Papaver/drug effects/genetics ; }, abstract = {BACKGROUND: Corn poppy (Papaver rhoeas) is the most damaging broadleaf weed in France. Massively parallel amplicon sequencing was used to investigate the prevalence, mode of evolution and spread of resistance-endowing ALS alleles in 422 populations randomly sampled throughout poppy's range in France. Bioassays were used to detect resistance to the synthetic auxin 2,4-D in 43 of these populations.

RESULTS: A total of 21 100 plants were analysed and 24 mutant ALS alleles carrying an amino-acid substitution involved or potentially involved in resistance were identified. The vast majority (97.6%) of the substitutions occurred at codon Pro197, where all six possible single-nucleotide non-synonymous substitutions plus four double-nucleotide substitutions were identified. Changes observed in the enzymatic properties of the mutant ALS isoforms could not explain the differences in prevalence among the corresponding alleles. Sequence read analysis showed that mutant ALS alleles had multiple, independent evolutionary origins, and could have evolved several times independently within an area of a few kilometres. Finally, 2,4-D resistance was associated with mutant ALS alleles in individual plants in one third of the populations assayed.

CONCLUSION: The intricate geographical mosaic of mutant ALS alleles observed is the likely result of the combination of huge population sizes, multiple independent mutation events and human-mediated spread of resistance. Our work highlights the ability of poppy populations and individual plants to accumulate different ALS alleles and as yet unknown mechanisms conferring resistance to synthetic auxins. This does not bode well for the continued use of chemical herbicides to control poppy. © 2023 Society of Chemical Industry.}, } @article {pmid37751856, year = {2023}, author = {Martin Schaff, C and Kurent, JE and Kolodziejczak, S and Milic, M and Foster, LA and Mehta, AK}, title = {Neuroprognostication for Patients with Amyotrophic Lateral Sclerosis: An Updated, Evidence-Based Review.}, journal = {Seminars in neurology}, volume = {43}, number = {5}, pages = {776-790}, doi = {10.1055/s-0043-1775595}, pmid = {37751856}, issn = {1098-9021}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/therapy ; Quality of Life ; Prognosis ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative disorder that presents and progresses in various ways, making prognostication difficult. Several paradigms exist for providers to elucidate prognosis in a way that addresses not only the amount of time a patient has to live, but also a patient's quality of their life moving forward. Prognostication, with regard to both survivability and quality of life, is impacted by several features that include, but are not limited to, patient demographics, clinical features on presentation, and over time, access to therapy, and access to multidisciplinary clinics. An understanding of the impact that these features have on the life of a patient with ALS can help providers to develop a better and more personalized approach for patients related to their clinical prognosis after a diagnosis is made. The ultimate goal of prognostication is to empower patients with ALS to take control and make decisions with their care teams to ensure that their goals are addressed and met.}, } @article {pmid37751804, year = {2023}, author = {Wang, Z and Zhang, C and Fan, C and Liu, Y}, title = {Post-translational modifications in stress granule and their implications in neurodegenerative diseases.}, journal = {Biochimica et biophysica acta. Gene regulatory mechanisms}, volume = {1866}, number = {4}, pages = {194989}, doi = {10.1016/j.bbagrm.2023.194989}, pmid = {37751804}, issn = {1876-4320}, mesh = {Humans ; *Neurodegenerative Diseases/genetics/metabolism ; Stress Granules ; Protein Processing, Post-Translational ; *Amyotrophic Lateral Sclerosis/genetics/pathology ; RNA, Messenger/metabolism ; }, abstract = {Stress granules (SGs) arise as formations of mRNAs and proteins in response to translation initiation inhibition during stress. These dynamic compartments adopt a fluidic nature through liquid-liquid phase separation (LLPS), exhibiting a composition subject to constant change within cellular contexts. Research has unveiled an array of post-translational modifications (PTMs) occurring on SG proteins, intricately orchestrating SG dynamics. In the realm of neurodegenerative diseases, pathological mutant proteins congregate into insoluble aggregates alongside numerous SG proteins, manifesting resilience against disassembly. Specific PTMs conspicuously label these aggregates, designating them for subsequent degradation. The strategic manipulation of aberrant SGs via PTMs emerges as a promising avenue for therapeutic intervention. This review discerns recent strides in comprehending the impact of PTMs on LLPS behavior and the assembly/disassembly kinetics of SGs. By delving into the roles of PTMs in governing SG dynamics, we augment our cognizance of the molecular underpinnings of neurodegeneration. Furthermore, we offer invaluable insights into potential targets for therapeutic intervention in neurodegenerative afflictions, encompassing conditions like amyotrophic lateral sclerosis and frontotemporal dementia.}, } @article {pmid37749234, year = {2023}, author = {Linsenmeier, M and Faltova, L and Morelli, C and Capasso Palmiero, U and Seiffert, C and Küffner, AM and Pinotsi, D and Zhou, J and Mezzenga, R and Arosio, P}, title = {The interface of condensates of the hnRNPA1 low-complexity domain promotes formation of amyloid fibrils.}, journal = {Nature chemistry}, volume = {15}, number = {10}, pages = {1340-1349}, pmid = {37749234}, issn = {1755-4349}, support = {101002094//EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council)/ ; }, abstract = {The maturation of liquid-like protein condensates into amyloid fibrils has been associated with several neurodegenerative diseases. However, the molecular mechanisms underlying this liquid-to-solid transition have remained largely unclear. Here we analyse the amyloid formation mediated by condensation of the low-complexity domain of hnRNPA1, a protein involved in amyotrophic lateral sclerosis. We show that phase separation and fibrillization are connected but distinct processes that are modulated by different regions of the protein sequence. By monitoring the spatial and temporal evolution of amyloid formation we demonstrate that the formation of fibrils does not occur homogeneously inside the droplets but is promoted at the interface of the condensates. We further show that coating the interface of the droplets with surfactant molecules inhibits fibril formation. Our results reveal that the interface of biomolecular condensates of hnRNPA1 promotes fibril formation, therefore suggesting interfaces as a potential novel therapeutic target against the formation of aberrant amyloids mediated by condensation.}, } @article {pmid37748881, year = {2023}, author = {McFarlane, R and Peelo, C and Galvin, M and Heverin, M and Hardiman, O}, title = {Epidemiologic Trends of Amyotrophic Lateral Sclerosis in Ireland, 1996-2021.}, journal = {Neurology}, volume = {101}, number = {19}, pages = {e1905-e1912}, pmid = {37748881}, issn = {1526-632X}, mesh = {Male ; Humans ; Female ; Middle Aged ; Aged ; *Amyotrophic Lateral Sclerosis/diagnosis ; Ireland/epidemiology ; Delayed Diagnosis ; Riluzole ; Proportional Hazards Models ; }, abstract = {BACKGROUND AND OBJECTIVES: The objective of this study was to examine changes to the incidence, prevalence, age at onset, and survival of patients diagnosed with amyotrophic lateral sclerosis (ALS) in the Republic of Ireland over 25 years.

METHODS: Incident and prevalent cases of ALS were estimated using the Irish population-based ALS Register, which has been in continuous operation since 1994. Incident cases were age standardized using the direct method and applied to 3 standard populations (Irish, European, and American). Survival was determined using Kaplan-Meier curves and Cox regression models. Non-normally distributed groups were compared using the Kruskal-Wallis test with a Bonferroni correction.

RESULTS: A total of 2,771 patients with ALS were identified in the Republic of Ireland over 25 years. Incidence per 100,000 was determined for the population older than 15 years. Crude incidence increased from 2.64 to 5.46 per 100,000. Standardized incidence increased from 2.64 to 3.1 per 100,000. Prevalence increased from 5.83 to 8.10 per 100,000. The median age at onset increased from 64 to 67 years. The peak age of incidence increased from those between 70 and 74 years to those between 75 and 79 years. Overall, women had a consistently later median age at onset of 67 years compared with men at 65 years (p < 0.001). No significant difference in survival was noted between those captured across 3 different epochs (1996-2003, 2004-2012, 2013-2021). Older age at onset (hazard ratio [HR] 1.03, CI 1.02-1.04, p < 0.001) was a negative predictive factor of survival in multivariate Cox regression analysis. Riluzole use (HR 0.67, CI 0.50-0.90, p = 0.033) and diagnostic delay (HR 0.98, CI 0.98-0.99, p < 0.001) were positive predictive factors.

DISCUSSION: Within the Republic of Ireland, the age-standardized overall incidence, peak incidence, prevalence, and age at onset of ALS have all increased over 25 years. Despite the widespread use of noninvasive ventilation, aggressive secretion management, and changes in ALS care, the mean survival within the Irish population has not changed.}, } @article {pmid37748861, year = {2023}, author = {Soustelle, L and Aimond, F and López-Andrés, C and Brugioti, V and Raoul, C and Layalle, S}, title = {ALS-Associated KIF5A Mutation Causes Locomotor Deficits Associated with Cytoplasmic Inclusions, Alterations of Neuromuscular Junctions, and Motor Neuron Loss.}, journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, volume = {43}, number = {47}, pages = {8058-8072}, pmid = {37748861}, issn = {1529-2401}, mesh = {Male ; Animals ; Female ; Humans ; *Amyotrophic Lateral Sclerosis/genetics/metabolism ; Kinesins/genetics/metabolism ; Genome-Wide Association Study ; *Neurodegenerative Diseases/metabolism ; Motor Neurons/metabolism ; Neuromuscular Junction/metabolism ; Mutation/genetics ; Drosophila/metabolism ; Inclusion Bodies/metabolism ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease affecting motor neurons. Recently, genome-wide association studies identified KIF5A as a new ALS-causing gene. KIF5A encodes a protein of the kinesin-1 family, allowing the anterograde transport of cargos along the microtubule rails in neurons. In ALS patients, mutations in the KIF5A gene induce exon 27 skipping, resulting in a mutated protein with a new C-terminal region (KIF5A Δ27). To understand how KIF5A Δ27 underpins the disease, we developed an ALS-associated KIF5A Drosophila model. When selectively expressed in motor neurons, KIF5A Δ27 alters larval locomotion as well as morphology and synaptic transmission at neuromuscular junctions in both males and females. We show that the distribution of mitochondria and synaptic vesicles is profoundly disturbed by KIF5A Δ27 expression. That is consistent with the numerous KIF5A Δ27-containing inclusions observed in motor neuron soma and axons. Moreover, KIF5A Δ27 expression leads to motor neuron death and reduces life expectancy. Our in vivo model reveals that a toxic gain of function underlies the pathogenicity of ALS-linked KIF5A mutant.SIGNIFICANCE STATEMENT Understanding how a mutation identified in patients with amyotrophic lateral sclerosis (ALS) causes the disease and the loss of motor neurons is crucial to fight against this disease. To this end, we have created a Drosophila model based on the motor neuron expression of the KIF5A mutant gene, recently identified in ALS patients. KIF5A encodes a kinesin that allows the anterograde transport of cargos. This model recapitulates the main features of ALS, including alterations of locomotion, synaptic neurotransmission, and morphology at neuromuscular junctions, as well as motor neuron death. KIF5A mutant is found in cytoplasmic inclusions, and its pathogenicity is because of a toxic gain of function.}, } @article {pmid37748443, year = {2024}, author = {Jütte, R}, title = {Involving Voters and Consumers in Decision-Making about the Health Care System - The Swiss Case: A Review.}, journal = {Complementary medicine research}, volume = {31}, number = {1}, pages = {78-83}, doi = {10.1159/000534268}, pmid = {37748443}, issn = {2504-2106}, mesh = {Humans ; Switzerland ; *Voting ; *Complementary Therapies ; Evidence-Based Medicine ; }, abstract = {BACKGROUND: Behind the principle of involving users and voters directly in decision-making about the health care system are ideas relating to empowerment. This implies a challenge to the traditional view that scientific knowledge is generally believed to be of higher value than empirical knowledge, as it is the case with CAM. The objectives of this review are (a) to show that this assumption disregards the fact that CAM is as scientific as conventional medicine but has different basic assumptions what the world is being made of and consequently uses different/adapted scientific methods; (b) to demonstrate how a perspective of the history of medicine and science as well as direct democracy mechanisms such as stipulated in the Swiss constitution can be used to achieve the acceptance of CAM in a modern medical health care system. A public health care system financed by levies from the population should also reflect the widely documented desire in the population for medical pluralism (provided that therapeutical alternatives are not risky). Otherwise, the problem of social inequality arises because only people with a good financial background can afford this medicine.

SUMMARY: From the perspective of scientific theory and the history of science, the answer to the question of whether complementary medicine and conventional medical procedures must provide proof of efficacy according to a uniform scientific is quite controversial according to epistemologically oriented studies on this issue.

KEY MESSAGES: This review found strong evidence for involving voters and consumers directly in decision-making about the provision of CAM in the health care system. It also seems necessary to step back in the debate on evidence-based medicine, taking a history of medicine and science perspective, as the role which the proper method occupies and plays in medicine is defined by the scientific nature of the world view.

UNLABELLED: Hinter dem Grundsatz, Nutzer und Wähler direkt in die Entscheidungsfindung über das Gesundheitssystem einzubeziehen, stehen Vorstellungen von Empowerment. Dies impliziert eine Infragestellung der traditionellen Ansicht, dass wissenschaftliches Wissen im Allgemeinen als wertvoller angesehen wird als empirisches Wissen und erprobte Erfahrung, wie es bei der Komplementärmedizin der Fall ist. Die Ziele dieser Übersichtsarbeit sind: (a) zu zeigen, dass diese Annahme die Tatsache außer Acht lässt, dass die Komplementärmedizin ebenso wissenschaftlich ist wie die Schulmedizin, aber von anderen Grundannahmen ausgeht, wie die Welt beschaffen ist, und folglich andere/angepasste wissenschaftliche Methoden anwendet; (b) aufzuzeigen, wie eine medizin- und wissenschaftsgeschichtliche Perspektive sowie Mechanismen der direkten Demokratie, wie sie in der Schweizer Verfassung vorgesehen sind, genutzt werden können, um die Akzeptanz der Komplementärmedizin in einem modernen medizinischen Gesundheitssystem zu erreichen. Ein öffentliches, durch Abgaben der Bevölkerung finanziertes Gesundheitssystem sollte auch dem vielfach dokumentierten Wunsch der Bevölkerung nach medizinischem Pluralismus Rechnung tragen (sofern die therapeutischen Alternativen nicht riskant sind). Andernfalls stellt sich das Problem der sozialen Ungleichheit, weil sich nur Menschen mit einem guten finanziellen Hintergrund diese Medizin leisten können.}, } @article {pmid37747929, year = {2023}, author = {Krupp, S and Hubbard, I and Tam, O and Hammell, GM and Dubnau, J}, title = {TDP-43 pathology in Drosophila induces glial-cell type specific toxicity that can be ameliorated by knock-down of SF2/SRSF1.}, journal = {PLoS genetics}, volume = {19}, number = {9}, pages = {e1010973}, pmid = {37747929}, issn = {1553-7404}, support = {R01 AG076493/AG/NIA NIH HHS/United States ; R01 AG078788/AG/NIA NIH HHS/United States ; RF1 AG057338/AG/NIA NIH HHS/United States ; RF1 AG076493/AG/NIA NIH HHS/United States ; }, mesh = {Animals ; *Amyotrophic Lateral Sclerosis/genetics ; Astrocytes/metabolism ; DNA-Binding Proteins/genetics/metabolism ; Drosophila/genetics/metabolism ; *Drosophila Proteins/genetics/metabolism ; *Frontotemporal Dementia ; Neurons/metabolism ; RNA Splicing Factors/metabolism ; }, abstract = {Accumulation of cytoplasmic inclusions of TAR-DNA binding protein 43 (TDP-43) is seen in both neurons and glia in a range of neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD) and Alzheimer's disease (AD). Disease progression involves non-cell autonomous interactions among multiple cell types, including neurons, microglia and astrocytes. We investigated the effects in Drosophila of inducible, glial cell type-specific TDP-43 overexpression, a model that causes TDP-43 protein pathology including loss of nuclear TDP-43 and accumulation of cytoplasmic inclusions. We report that TDP-43 pathology in Drosophila is sufficient to cause progressive loss of each of the 5 glial sub-types. But the effects on organismal survival were most pronounced when TDP-43 pathology was induced in the perineural glia (PNG) or astrocytes. In the case of PNG, this effect is not attributable to loss of the glial population, because ablation of these glia by expression of pro-apoptotic reaper expression has relatively little impact on survival. To uncover underlying mechanisms, we used cell-type-specific nuclear RNA sequencing to characterize the transcriptional changes induced by pathological TDP-43 expression. We identified numerous glial cell-type specific transcriptional changes. Notably, SF2/SRSF1 levels were found to be decreased in both PNG and in astrocytes. We found that further knockdown of SF2/SRSF1 in either PNG or astrocytes lessens the detrimental effects of TDP-43 pathology on lifespan, but extends survival of the glial cells. Thus TDP-43 pathology in astrocytes or PNG causes systemic effects that shorten lifespan and SF2/SRSF1 knockdown rescues the loss of these glia, and also reduces their systemic toxicity to the organism.}, } @article {pmid37747630, year = {2023}, author = {Oh, JE and Oh, JA and Demopoulos, M and Clark, KM and Phillips, MC}, title = {Impact of the metabolic syndrome on prevalence and survival in motor neuron disease: a retrospective case series.}, journal = {Metabolic brain disease}, volume = {38}, number = {8}, pages = {2583-2589}, pmid = {37747630}, issn = {1573-7365}, support = {Waikato Hospital Neurology Research Fund//Waikato Hospital Neurology Research Fund/ ; }, mesh = {Prevalence ; Retrospective Studies ; *Amyotrophic Lateral Sclerosis ; *Motor Neuron Disease/epidemiology/complications/diagnosis ; *Metabolic Syndrome/epidemiology/complications ; Humans ; Australasian People ; Maori People ; }, abstract = {Metabolic dysfunction is an important factor in the pathogenesis of motor neuron disease, but its prevalence and association with survival in this disorder is unknown. We hypothesized that patients with motor neuron disease would show a higher prevalence of metabolic syndrome compared to the general New Zealand population, and that metabolic syndrome would be associated with worsened survival. We undertook a retrospective analysis in 109 motor neuron disease patients diagnosed and treated at Waikato Hospital from 2013 to 2020. Demographic, clinical, and laboratory data were collected. Survival was defined as the date of initial symptom onset to the date of death. Of 104 eligible patients, 34 patients (33%) had metabolic syndrome (33% of Europeans, 46% of Māori). Mean survival in motor neuron disease patients with metabolic syndrome was significantly reduced compared to patients without metabolic syndrome (38 vs. 61 months, P = 0.044), with a 5-year survival rate of 21% for the former and 38% for the latter (P = 0.012). Compared with the general New Zealand population, metabolic syndrome is highly prevalent amongst motor neuron disease patients in the Waikato region and it is associated with worsened survival. Metabolic dysfunction may be a key factor underlying the pathogenesis of motor neuron disease.}, } @article {pmid37747451, year = {2023}, author = {Brisley, A and Lambert, H and Rodrigues, C}, title = {Antibiotics in Catalan Primary Care: Prescription, Use and Remedies for a Crisis of Care.}, journal = {Medical anthropology}, volume = {42}, number = {7}, pages = {682-696}, pmid = {37747451}, issn = {1545-5882}, support = {/WT_/Wellcome Trust/United Kingdom ; 210359/Z/18/Z/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Humans ; *Anti-Bacterial Agents/therapeutic use ; Anthropology, Medical ; *Prescriptions ; Primary Health Care ; Europe ; }, abstract = {Antimicrobial resistance is one of the twenty-first century's major health challenges. Linked to the extensive use of antibiotics and other antimicrobials, resistance occurs when microbes stop responding to medications. Rates of antibiotic consumption in Spain are among the highest in Europe. Drawing on research conducted in Catalonia, in this article we present findings from ethnographic fieldwork and semi-structured interviews with general practitioners, residents of Barcelona, and professionals who have worked in antibiotic stewardship. We argue that the circulation of antibiotics should be understood in relation to broader historical processes and the deficient systems of health and social care provision they have produced.}, } @article {pmid37746849, year = {2023}, author = {Martino, J and Liu, Q and Vukojevic, K and Ke, J and Lim, TY and Khan, A and Gupta, Y and Perez, A and Yan, Z and Milo Rasouly, H and Vena, N and Lippa, N and Giordano, JL and Saraga, M and Saraga-Babic, M and Westland, R and Bodria, M and Piaggio, G and Bendapudi, PK and Iglesias, AD and Wapner, RJ and Tasic, V and Wang, F and Ionita-Laza, I and Ghiggeri, GM and Kiryluk, K and Sampogna, RV and Mendelsohn, CL and D'Agati, VD and Gharavi, AG and Sanna-Cherchi, S}, title = {Mouse and human studies support DSTYK loss of function as a low-penetrance and variable expressivity risk factor for congenital urinary tract anomalies.}, journal = {Genetics in medicine : official journal of the American College of Medical Genetics}, volume = {25}, number = {12}, pages = {100983}, doi = {10.1016/j.gim.2023.100983}, pmid = {37746849}, issn = {1530-0366}, support = {U54 DK104309/DK/NIDDK NIH HHS/United States ; K25 DK128563/DK/NIDDK NIH HHS/United States ; P20 DK116191/DK/NIDDK NIH HHS/United States ; R01 DK103184/DK/NIDDK NIH HHS/United States ; R01 DK115574/DK/NIDDK NIH HHS/United States ; T35 DK093430/DK/NIDDK NIH HHS/United States ; R01 DK080099/DK/NIDDK NIH HHS/United States ; }, mesh = {*Urogenital Abnormalities/genetics ; Vesico-Ureteral Reflux ; Mice, Inbred C3H ; Mice, Inbred C57BL ; *Urinary Tract ; Receptor-Interacting Protein Serine-Threonine Kinases/genetics ; Risk Factors ; Penetrance ; Humans ; Mice ; Animals ; *Epilepsy/genetics ; Kidney/abnormalities ; }, abstract = {PURPOSE: Previous work identified rare variants in DSTYK associated with human congenital anomalies of the kidney and urinary tract (CAKUT). Here, we present a series of mouse and human studies to clarify the association, penetrance, and expressivity of DSTYK variants.

METHODS: We phenotypically characterized Dstyk knockout mice of 3 separate inbred backgrounds and re-analyzed the original family segregating the DSTYK c.654+1G>A splice-site variant (referred to as "SSV" below). DSTYK loss of function (LOF) and SSVs were annotated in individuals with CAKUT, epilepsy, or amyotrophic lateral sclerosis vs controls. A phenome-wide association study analysis was also performed using United Kingdom Biobank (UKBB) data.

RESULTS: Results demonstrate ∼20% to 25% penetrance of obstructive uropathy, at least, in C57BL/6J and FVB/NJ Dstyk[-/-] mice. Phenotypic penetrance increased to ∼40% in C3H/HeJ mutants, with mild-to-moderate severity. Re-analysis of the original family segregating the rare SSV showed low penetrance (43.8%) and no alternative genetic causes for CAKUT. LOF DSTYK variants burden showed significant excess for CAKUT and epilepsy vs controls and an exploratory phenome-wide association study supported association with neurological disorders.

CONCLUSION: These data support causality for DSTYK LOF variants and highlights the need for large-scale sequencing studies (here >200,000 cases) to accurately assess causality for genes and variants to lowly penetrant traits with common population prevalence.}, } @article {pmid37746513, year = {2023}, author = {Singh, A and Arora, S and Chavan, M and Shahbaz, S and Jabeen, H}, title = {An Overview of the Neurotrophic and Neuroprotective Properties of the Psychoactive Drug Lithium as an Autophagy Modulator in Neurodegenerative Conditions.}, journal = {Cureus}, volume = {15}, number = {8}, pages = {e44051}, pmid = {37746513}, issn = {2168-8184}, abstract = {For both short-term and long-term treatment of bipolar disorder, lithium is a prototypical mood stabilizer. Lithium's neuroprotective properties were revealed by cumulative translational research, which opened the door to reforming the chemical as a treatment for neurodegenerative illnesses. The control of homeostatic systems such as oxidative stress, autophagy, apoptosis, mitochondrial function, and inflammation underlies lithium's neuroprotective characteristics. The fact that lithium inhibits the enzymes inositol monophosphatase (IMPase) and glycogen synthase kinase (GSK)-3 may be the cause of the various intracellular reactions. In this article, we review lithium's neurobiological properties, as demonstrated by its neurotrophic and neuroprotective capabilities, as well as translational studies in cells in culture and in animal models of Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), Prion disease, amyotrophic lateral sclerosis (ALS), ischemic stroke, and neuronal ceroid lipofuscinosis (NCL), discussing the justification for the drug's use in the treatment of these neurodegenerative disorders.}, } @article {pmid37746061, year = {2023}, author = {Bennett, SA and Cobos, SN and Son, E and Segal, R and Mathew, S and Yousuf, H and Torrente, MP}, title = {Impaired RNA Binding Does Not Prevent Histone Modification Changes in a FUS ALS/FTD Yeast Model.}, journal = {microPublication biology}, volume = {2023}, number = {}, pages = {}, pmid = {37746061}, issn = {2578-9430}, support = {R15 NS125394/NS/NINDS NIH HHS/United States ; }, abstract = {Mutations in the RNA-binding protein FUS are linked to amyotrophic lateral sclerosis and frontotemporal dementia (ALS/FTD). FUS mutants mislocalize and aggregate in dying neurons. We previously established that FUS proteinopathy is linked to changes in the histone modification landscape in a yeast ALS/FTD model. Here, we examine whether FUS' RNA binding is necessary for this connection. We find that overexpression of a FUS mutant unable to bind RNA is still associated with reduced levels of H3S10ph, H3K14ac and H3K56ac. Hence, FUS' ability to bind RNA is not required in the mechanism connecting FUS proteinopathy to altered histone post-translational modifications.}, } @article {pmid37745492, year = {2024}, author = {Hwang, RD and Lu, Y and Tang, Q and Periz, G and Park, G and Li, X and Xiang, Q and Liu, Y and Zhang, T and Wang, J}, title = {DBT is a metabolic switch for maintenance of proteostasis under proteasomal impairment.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2023.09.12.556394}, pmid = {37745492}, issn = {2692-8205}, abstract = {Proteotoxic stress impairs cellular homeostasis and underlies the pathogenesis of many neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). The proteasomal and autophagic degradation of proteins are two major pathways for protein quality control in the cell. Here, we report a genome-wide CRISPR screen uncovering a major regulator of cytotoxicity resulting from the inhibition of the proteasome. Dihydrolipoamide branched chain transacylase E2 (DBT) was found to be a robust suppressor, the loss of which protects against proteasome inhibition-associated cell death through promoting clearance of ubiquitinated proteins. Loss of DBT altered the metabolic and energetic status of the cell and resulted in activation of autophagy in an AMP-activated protein kinase (AMPK)-dependent mechanism in the presence of proteasomal inhibition. Loss of DBT protected against proteotoxicity induced by ALS-linked mutant TDP-43 in Drosophila and mammalian neurons. DBT is upregulated in the tissues from ALS patients. These results demonstrate that DBT is a master switch in the metabolic control of protein quality control with implications in neurodegenerative diseases.}, } @article {pmid37745304, year = {2023}, author = {Yokota, M and Yoshino, Y and Hosoi, M and Hashimoto, R and Kakuta, S and Shiga, T and Ishikawa, KI and Okano, H and Hattori, N and Akamatsu, W and Koike, M}, title = {Reduced ER-mitochondrial contact sites and mitochondrial Ca[2+] flux in PRKN-mutant patient tyrosine hydroxylase reporter iPSC lines.}, journal = {Frontiers in cell and developmental biology}, volume = {11}, number = {}, pages = {1171440}, pmid = {37745304}, issn = {2296-634X}, abstract = {Endoplasmic reticulum-mitochondrial contact sites (ERMCS) play an important role in mitochondrial dynamics, calcium signaling, and autophagy. Disruption of the ERMCS has been linked to several neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). However, the etiological role of ERMCS in these diseases remains unclear. We previously established tyrosine hydroxylase reporter (TH-GFP) iPSC lines from a PD patient with a PRKN mutation to perform correlative light-electron microscopy (CLEM) analysis and live cell imaging in GFP-expressing dopaminergic neurons. Here, we analyzed ERMCS in GFP-expressing PRKN-mutant dopaminergic neurons from patients using CLEM and a proximity ligation assay (PLA). The PLA showed that the ERMCS were significantly reduced in PRKN-mutant patient dopaminergic neurons compared to the control under normal conditions. The reduction of the ERMCS in PRKN-mutant patient dopaminergic neurons was further enhanced by treatment with a mitochondrial uncoupler. In addition, mitochondrial calcium imaging showed that mitochondrial Ca[2+] flux was significantly reduced in PRKN-mutant patient dopaminergic neurons compared to the control. These results suggest a defect in calcium flux from ER to mitochondria is due to the decreased ERMCS in PRKN-mutant patient dopaminergic neurons. Our study of ERMCS using TH-GFP iPSC lines would contribute to further understanding of the mechanisms of dopaminergic neuron degeneration in patients with PRKN mutations.}, } @article {pmid37744877, year = {2023}, author = {Wilkins, JM and Gakh, O and Guo, Y and Popescu, B and Staff, NP and Lucchinetti, CF}, title = {Biomolecular alterations detected in multiple sclerosis skin fibroblasts using Fourier transform infrared spectroscopy.}, journal = {Frontiers in cellular neuroscience}, volume = {17}, number = {}, pages = {1223912}, pmid = {37744877}, issn = {1662-5102}, abstract = {Multiple sclerosis (MS) is the leading cause of non-traumatic disability in young adults. New avenues are needed to help predict individuals at risk for developing MS and aid in diagnosis, prognosis, and outcome of therapeutic treatments. Previously, we showed that skin fibroblasts derived from patients with MS have altered signatures of cell stress and bioenergetics, which likely reflects changes in their protein, lipid, and biochemical profiles. Here, we used Fourier transform infrared (FTIR) spectroscopy to determine if the biochemical landscape of MS skin fibroblasts were altered when compared to age- and sex-matched controls (CTRL). More so, we sought to determine if FTIR spectroscopic signatures detected in MS skin fibroblasts are disease specific by comparing them to amyotrophic lateral sclerosis (ALS) skin fibroblasts. Spectral profiling of skin fibroblasts from MS individuals suggests significant alterations in lipid and protein organization and homeostasis, which may be affecting metabolic processes, cellular organization, and oxidation status. Sparse partial least squares-discriminant analysis of spectral profiles show that CTRL skin fibroblasts segregate well from diseased cells and that changes in MS and ALS may be unique. Differential changes in the spectral profile of CTRL, MS, and ALS cells support the development of FTIR spectroscopy to detect biomolecular modifications in patient-derived skin fibroblasts, which may eventually help establish novel peripheral biomarkers.}, } @article {pmid37741764, year = {2024}, author = {Ducharme, S and Pijnenburg, Y and Rohrer, JD and Huey, E and Finger, E and Tatton, N}, title = {Identifying and Diagnosing TDP-43 Neurodegenerative Diseases in Psychiatry.}, journal = {The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry}, volume = {32}, number = {1}, pages = {98-113}, pmid = {37741764}, issn = {1545-7214}, support = {U01 AG079850/AG/NIA NIH HHS/United States ; R01 MH120794/MH/NIMH NIH HHS/United States ; R01 AG062268/AG/NIA NIH HHS/United States ; MR/T046015/1/MRC_/Medical Research Council/United Kingdom ; MR/M008525/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/genetics ; DNA-Binding Proteins/genetics ; *Frontotemporal Dementia/diagnosis/genetics ; *Neurodegenerative Diseases/diagnosis/genetics ; *Psychiatry ; }, abstract = {Neuropsychiatric symptoms (NPS) are common manifestations of neurodegenerative disorders and are often early signs of those diseases. Among those neurodegenerative diseases, TDP-43 proteinopathies are an increasingly recognized cause of early neuropsychiatric manifestations. TDP-43-related diseases include frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS), and Limbic-Predominant Age-Related TDP-43 Encephalopathy (LATE). The majority of TDP-43-related diseases are sporadic, but a significant proportion is hereditary, with progranulin (GRN) mutations and C9orf72 repeat expansions as the most common genetic etiologies. Studies reveal that NPS can be the initial manifestation of those diseases or can complicate disease course, but there is a lack of awareness among clinicians about TDP-43-related diseases, which leads to common diagnostic mistakes or delays. There is also emerging evidence that TDP-43 accumulations could play a role in late-onset primary psychiatric disorders. In the absence of robust biomarkers for TDP-43, the diagnosis remains primarily based on clinical assessment and neuroimaging. Given the association with psychiatric symptoms, clinical psychiatrists have a key role in the early identification of patients with TDP-43-related diseases. This narrative review provides a comprehensive overview of the pathobiology of TDP-43, resulting clinical presentations, and associated neuropsychiatric manifestations to help guide clinical practice.}, } @article {pmid37741265, year = {2024}, author = {Li, M and Zhang, L and Jiang, LL and Zhao, ZB and Long, YH and Chen, DM and Bin, J and Kang, C and Liu, YJ}, title = {Label-free Raman microspectroscopic imaging with chemometrics for cellular investigation of apple ring rot and nondestructive early recognition using near-infrared reflection spectroscopy with machine learning.}, journal = {Talanta}, volume = {267}, number = {}, pages = {125212}, doi = {10.1016/j.talanta.2023.125212}, pmid = {37741265}, issn = {1873-3573}, mesh = {Machine Learning ; *Malus ; Chemometrics ; Spectroscopy, Near-Infrared/methods ; Ascomycota ; Pectins ; }, abstract = {Apple ring rot caused by Botryosphaeria dothidea can cause fruit decay during the growth and storage stages of apple fruit. Understanding the infection process and cellular defense response at the cellular micro-level holds immense importance in the field of prevention and control. Consequently, there is a pressing need to develop suitable chemical imaging analysis methods. Here we proposed a label-free, high-throughput imaging method for cellular investigation of apple fruit ring rot infected by Botryosphaeria dothidea, based on confocal Raman microspectroscopic imaging technology combined with multivariate curve resolution-alternating least squares algorithm (MCR-ALS). We conducted Raman measurements on every apple fruit and obtain an image cube. This cube was then unfolded into an augmented matrix in a column-wise manner. We proceeded with simultaneous MCR-ALS analysis, resolving the single-substance spectrum and concentration profile from the mixed signals. Lastly, the accurate and pure molecular imaging of low methoxyl pectin, high methoxyl pectin, cellulose, lignin, and phenols were realized by refolding the resolved concentration data to construct the composition image. Thereafter, we realized the study of the spatial-temporal changes distribution of the above substances in the cuticle and cell wall of green and red apples at different stages of infection. The imaging method proposed in this paper is expected to provide a chemical imaging strategy for studying pathogen infection process and fruit defense response at the cellular level. In addition, by utilizing a fiber-optic probe near-infrared reflection spectrometer in conjunction with machine learning, we developed a rapid and non-destructive classification method. This method allows for the timely identification of apples exhibiting early infection by Botryosphaeria dothidea. Notably, both principal component analysis-quadratic discriminant analysis and support vector machine achieved a classification accuracy of 100%.}, } @article {pmid37741154, year = {2023}, author = {Wabwile, JM and Angeyo, HK and Massop, AD}, title = {Exploring band-free Raman microspectrometry combined with PCA and MCR-ALS for size-resolved forensic analysis of uranium in aerosols in a model nuclear atmosphere.}, journal = {Journal of environmental radioactivity}, volume = {270}, number = {}, pages = {107295}, doi = {10.1016/j.jenvrad.2023.107295}, pmid = {37741154}, issn = {1879-1700}, mesh = {*Radiation Monitoring ; *Uranium/analysis ; Least-Squares Analysis ; Principal Component Analysis ; Aerosols/analysis ; Atmosphere ; }, abstract = {Achieving non-destructive micrometer-scale molecular and structural analysis of uranic materials in atmospheric aerosols with traditional methodologies is a challenge. Spatially resolved analysis of uranium in actinide-bearing aerosols is critical for nuclear forensics. Although laser Raman microspectrometry enables this, for the normally low uranium concentrations in the aerosols the spectra are indiscernible (band-free) against pronounced background: trace analysis requires a push in analytical strategy. We combined laser Raman microspectrometry (utilizing two lasers (λ = 532 nm, λ = 785 nm)) with principal component analysis (PCA) and multivariate curve resolution-alternate least squares (MCR-ALS) to perform size-resolved analysis of uranium in aerosols. Uranium-specific Raman scatter bands corresponding to uranyl nitrate (860 cm[-1]), uranium sulphate (868 cm[-1]), uranyl chloride (816 cm[-1]) and uranium trioxide (839 cm[-1]) were detected. The 816 cm[-1], 854 cm[-1], 868 cm[-1] bands were resolved by MCR-ALS and used to identify and map uranium in PM4.5 size aerosols. Based on spectral feature selection of the signature bands, PCA identified two sources of aerosol particles in model nuclear atmosphere - Sea spray for PM4.5 and re-suspension of 'nuclear' dust from a rare earth element (REE) mine for PM2.5. The MCR-ALS-resolved uranium bands showed the potential for attributive nuclear forensic analysis.}, } @article {pmid37740686, year = {2023}, author = {Vucic, S and Kiernan, MC}, title = {Nanocrystalline gold (CNM-Au8): a novel bioenergetic treatment for ALS.}, journal = {Expert opinion on investigational drugs}, volume = {32}, number = {9}, pages = {783-785}, doi = {10.1080/13543784.2023.2263368}, pmid = {37740686}, issn = {1744-7658}, } @article {pmid37739217, year = {2023}, author = {Chakraborty, J and Chakraborty, S and Chakraborty, S and Narayan, MN}, title = {Entanglement of MAPK pathways with gene expression and its omnipresence in the etiology for cancer and neurodegenerative disorders.}, journal = {Biochimica et biophysica acta. Gene regulatory mechanisms}, volume = {1866}, number = {4}, pages = {194988}, doi = {10.1016/j.bbagrm.2023.194988}, pmid = {37739217}, issn = {1876-4320}, mesh = {Humans ; Mitogen-Activated Protein Kinases ; MAP Kinase Signaling System/genetics ; *Neoplasms/genetics/drug therapy ; *Neurodegenerative Diseases/genetics ; Gene Expression ; }, abstract = {Mitogen Activated Protein Kinase (MAPK) is one of the most well characterized cellular signaling pathways that controls fundamental cellular processes including proliferation, differentiation, and apoptosis. These cellular functions are consequences of transcription of regulatory genes that are influenced and regulated by the MAP-Kinase signaling cascade. MAP kinase components such as Receptor Tyrosine Kinases (RTKs) sense external cues or ligands and transmit these signals via multiple protein complexes such as RAS-RAF, MEK, and ERKs and eventually modulate the transcription factors inside the nucleus to induce transcription and other regulatory functions. Aberrant activation, dysregulation of this signaling pathway, and genetic alterations in any of these components results in the developmental disorders, cancer, and neurodegenerative disorders. Over the years, the MAPK pathway has been a prime pharmacological target, to treat complex human disorders that are genetically linked such as cancer, Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. The current review re-visits the mechanism of MAPK pathways in gene expression regulation. Further, a current update on the progress of the mechanistic understanding of MAPK components is discussed from a disease perspective.}, } @article {pmid37739207, year = {2023}, author = {Verdile, V and Palombo, R and Ferrante, G and Ferri, A and Amadio, S and Volonté, C and Paronetto, MP}, title = {Dysregulation of alternative splicing underlies synaptic defects in familial amyotrophic lateral sclerosis.}, journal = {Progress in neurobiology}, volume = {231}, number = {}, pages = {102529}, doi = {10.1016/j.pneurobio.2023.102529}, pmid = {37739207}, issn = {1873-5118}, mesh = {Humans ; Animals ; *Amyotrophic Lateral Sclerosis/genetics/metabolism ; Alternative Splicing/genetics ; *Neurodegenerative Diseases/metabolism ; Motor Neurons/metabolism ; Superoxide Dismutase-1/genetics ; Disease Models, Animal ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease characterized by the degeneration of upper and lower motor neurons, progressive wasting and paralysis of voluntary muscles. A hallmark of ALS is the frequent nuclear loss and cytoplasmic accumulation of RNA binding proteins (RBPs) in motor neurons (MN), which leads to aberrant alternative splicing regulation. However, whether altered splicing patterns are also present in familial models of ALS without mutations in RBP-encoding genes has not been investigated yet. Herein, we found that altered splicing of synaptic genes is a common trait of familial ALS MNs. Similar deregulation was also observed in hSOD1[G93A] MN-like cells. In silico analysis identified the potential regulators of these pre-mRNAs, including the RBP Sam68. Immunofluorescence analysis and biochemical fractionation experiments revealed that Sam68 accumulates in the cytoplasmic insoluble ribonucleoprotein fraction of MN. Remarkably, the synaptic splicing events deregulated in ALS MNs were also affected in Sam68[-/-] spinal cords. Recombinant expression of Sam68 protein was sufficient to rescue these splicing changes in ALS hSOD1[G93A] MN-like cells. Hence, our study highlights an aberrant function of Sam68, which leads to splicing changes in synaptic genes and may contribute to the MN phenotype that characterizes ALS.}, } @article {pmid37739033, year = {2023}, author = {Tanaka, Y and Ito, SI and Honma, Y and Hasegawa, M and Kametani, F and Suzuki, G and Kozuma, L and Takeya, K and Eto, M}, title = {Dysregulation of the progranulin-driven autophagy-lysosomal pathway mediates secretion of the nuclear protein TDP-43.}, journal = {The Journal of biological chemistry}, volume = {299}, number = {11}, pages = {105272}, pmid = {37739033}, issn = {1083-351X}, mesh = {Humans ; *Autophagy/drug effects/genetics ; *DNA-Binding Proteins/genetics/metabolism ; HeLa Cells ; Intercellular Signaling Peptides and Proteins/genetics/metabolism ; *Lysosomes/metabolism ; *Progranulins/genetics/metabolism ; Microtubule-Associated Proteins/genetics/metabolism ; Gene Expression Regulation/drug effects ; Extracellular Vesicles/metabolism ; Enzyme Inhibitors/pharmacology ; Autophagosomes/drug effects/metabolism ; Autophagy-Related Proteins/genetics/metabolism ; }, abstract = {The cytoplasmic accumulation of the nuclear protein transactive response DNA-binding protein 43 kDa (TDP-43) has been linked to the progression of amyotrophic lateral sclerosis and frontotemporal lobar degeneration. TDP-43 secreted into the extracellular space has been suggested to contribute to the cell-to-cell spread of the cytoplasmic accumulation of TDP-43 throughout the brain; however, the underlying mechanisms remain unknown. We herein demonstrated that the secretion of TDP-43 was stimulated by the inhibition of the autophagy-lysosomal pathway driven by progranulin (PGRN), a causal protein of frontotemporal lobar degeneration. Among modulators of autophagy, only vacuolar-ATPase inhibitors, such as bafilomycin A1 (Baf), increased the levels of the full-length and cleaved forms of TDP-43 and the autophagosome marker LC3-II (microtubule-associated proteins 1A/1B light chain 3B) in extracellular vesicle fractions prepared from the culture media of HeLa, SH-SY5Y, or NSC-34 cells, whereas vacuolin-1, MG132, chloroquine, rapamycin, and serum starvation did not. The C-terminal fragment of TDP-43 was required for Baf-induced TDP-43 secretion. The Baf treatment induced the translocation of the aggregate-prone GFP-tagged C-terminal fragment of TDP-43 and mCherry-tagged LC3 to the plasma membrane. The Baf-induced secretion of TDP-43 was attenuated in autophagy-deficient ATG16L1 knockout HeLa cells. The knockdown of PGRN induced the secretion of cleaved TDP-43 in an autophagy-dependent manner in HeLa cells. The KO of PGRN in mouse embryonic fibroblasts increased the secretion of the cleaved forms of TDP-43 and LC3-II. The treatment inducing TDP-43 secretion increased the nuclear translocation of GFP-tagged transcription factor EB, a master regulator of the autophagy-lysosomal pathway in SH-SY5Y cells. These results suggest that the secretion of TDP-43 is promoted by dysregulation of the PGRN-driven autophagy-lysosomal pathway.}, } @article {pmid37738797, year = {2023}, author = {Dong, W and Peng, Q and Liu, Z and Xie, Z and Guo, X and Li, Y and Chen, C}, title = {Estrogen plays an important role by influencing the NLRP3 inflammasome.}, journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie}, volume = {167}, number = {}, pages = {115554}, doi = {10.1016/j.biopha.2023.115554}, pmid = {37738797}, issn = {1950-6007}, abstract = {The nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome is an important part of the natural immune system that plays an important role in many diseases. Estrogen is a sex hormone that plays an important role in controlling reproduction and regulates many physiological and pathological processes. Recent studies have indicated that estrogen is associated with disease progression. Estrogen can ameliorate some diseases (e. g, sepsis, mood disturbances, cerebral ischemia, some hepatopathy, Parkinson's disease, amyotrophic lateral sclerosis, inflammatory bowel disease, spinal cord injury, multiple sclerosis, myocardial ischemia/reperfusion injury, osteoarthritis, and renal fibrosis) by inhibiting the NLRP3 inflammasome. Estrogen can also promote the development of diseases (e.g., ovarian endometriosis, dry eye disease, and systemic lupus erythematosus) by upregulating the NLRP3 inflammasome. In addition, estrogen has a dual effect on the development of cancers and asthma. However, the mechanism of these effects is not summarized. This article reviewed the progress in understanding the effects of estrogen on the NLRP3 inflammasome and its mechanisms in recent years to provide a theoretical basis for an in-depth study.}, } @article {pmid37737151, year = {2024}, author = {Cabona, C and Ferraro, PM and Scialò, C and Bandettini Di Poggio, M and Novi, G and Gemelli, C and Vignolo, M and Rao, F and Capovilla, M and Marogna, M and Mandich, P and Origone, P and Schenone, A and Caponnetto, C}, title = {Clinical epidemiology of amyotrophic lateral sclerosis in Liguria, Italy: a ten year follow up study.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {25}, number = {1-2}, pages = {104-111}, doi = {10.1080/21678421.2023.2260842}, pmid = {37737151}, issn = {2167-9223}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/epidemiology/therapy ; Follow-Up Studies ; Prospective Studies ; Delayed Diagnosis ; Italy/epidemiology ; }, abstract = {OBJECTIVE: This article presents an updated analysis of the LIGALS register, a prospective study conducted over a ten-year period (2009-2018) in Liguria, Italy, aimed at evaluating the incidence, prevalence, clinical presentation, and management of amyotrophic lateral sclerosis (ALS).

METHODS: We calculated the mean annual crude incidence rate of ALS, assessed the point prevalence of ALS on January 1, 2018, and analyzed demographic factors, clinical characteristics, and clinical management strategies. Data analysis included Cox regression analysis to identify predictors of survival.

RESULTS: The mean annual crude incidence rate of ALS was 3.16/100,000 per year (CI 95%) while the point prevalence of ALS on January 1, 2018, was 9.31/100,000 population (CI 95%). Among the patients, 6.5% were familial ALS, while 93.5% were sporadic cases. Clinical management strategies, including percutaneous endoscopic gastrostomy (PEG) and noninvasive ventilation (NIV), were employed. The study observed a stable frequency of NIV initiation and PEG placement over time, with a growing trend toward earlier PEG positioning. The mean survival from symptom onset was 39 months, whereas from diagnosis, it was 26 months. Cox regression analysis identified several predictors of survival, including gender, age at onset and diagnosis, site of onset, diagnostic category, phenotype, and diagnostic delay.

CONCLUSIONS: This comprehensive analysis provides valuable insights into the long-term trends in ALS epidemiology and clinical management in Liguria, Italy. It underscores the importance of continued research efforts in understanding and addressing the challenges posed by ALS, particularly in terms of early diagnosis and optimizing clinical interventions to improve patient outcomes.}, } @article {pmid37736795, year = {2024}, author = {Liu, WS and Zhang, YR and Ge, YJ and Wang, HF and Cheng, W and Yu, JT}, title = {Inflammation and Brain Structure in Alzheimer's Disease and Other Neurodegenerative Disorders: a Mendelian Randomization Study.}, journal = {Molecular neurobiology}, volume = {61}, number = {3}, pages = {1593-1604}, pmid = {37736795}, issn = {1559-1182}, mesh = {Humans ; *Alzheimer Disease/genetics/metabolism ; *Amyotrophic Lateral Sclerosis/genetics ; Genome-Wide Association Study ; Mendelian Randomization Analysis ; *Neurodegenerative Diseases/genetics ; *Parkinson Disease/genetics ; Brain/metabolism ; Inflammation/genetics ; Cytokines/genetics/metabolism ; *Encephalitis ; }, abstract = {Previous in vitro and post-mortem studies have reported the role of inflammation in neurodegenerative disorders. However, the association between inflammation and brain structure in vivo and the transcriptome-driven functional basis with relevance to neurodegenerative disorders remains elusive. The aim of the present study is to identify the association among inflammation, brain structure, and neurodegenerative disorders at genetic and transcriptomic levels. Genetic variants associated with inflammatory cytokines were selected from the latest and largest genome-wide association studies of European ancestry. Neurodegenerative disorders including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and dementia with Lewy bodies (DLB) and brain structure imaging measures were selected as the outcomes. Two-sample Mendelian randomization analyses were conducted to identify the causal associations. Single-nucleus transcriptome data of the occipitotemporal cortex was further analyzed to identify the differential expressed genes in AD, which were tested for biological processes and protein interaction network. MR analysis indicated that genetically predicted TREM2 and sTREM2 were significantly associated with AD (TREM2: z-score = -9.088, p-value = 1.02 × 10[-19]; sTREM2: z-score = -7.495, p-value = 6.61 × 10[-14]). The present study found no evidence to support the causal associations between other inflammatory cytokines and the risks of AD, PD, ALS, or DLB. Genetically predicted TREM2 was significantly associated with the cortical thickness of inferior temporal (z-score = -4.238, p-value = 2.26 × 10[-5]) and pole temporal (z-score = -4.549, p-value = 5.40 × 10[-6]). In the occipitotemporal cortex samples, microglia were the main source of TREM2 gene and showed increasing expression of genes associated with inflammation and immunity. The present study has leveraged genetic and transcriptomic data to identify the association among TREM2, temporal lobe, and AD and the underlying cellular and molecular basis, thus providing a new perspective on the role of TREM2 in AD and insights into the complex associations among inflammation, brain structure, and neurodegenerative disorders, particularly AD.}, } @article {pmid37736756, year = {2023}, author = {Vahsen, BF and Nalluru, S and Morgan, GR and Farrimond, L and Carroll, E and Xu, Y and Cramb, KML and Amein, B and Scaber, J and Katsikoudi, A and Candalija, A and Carcolé, M and Dafinca, R and Isaacs, AM and Wade-Martins, R and Gray, E and Turner, MR and Cowley, SA and Talbot, K}, title = {C9orf72-ALS human iPSC microglia are pro-inflammatory and toxic to co-cultured motor neurons via MMP9.}, journal = {Nature communications}, volume = {14}, number = {1}, pages = {5898}, pmid = {37736756}, issn = {2041-1723}, support = {102176/Z/13/Z/WT_/Wellcome Trust/United Kingdom ; MR/N013468/1/MRC_/Medical Research Council/United Kingdom ; WADE-MARTINS/OCT13/867-792/MNDA_/Motor Neurone Disease Association/United Kingdom ; 203141/Z/16/Z/WT_/Wellcome Trust/United Kingdom ; /DH_/Department of Health/United Kingdom ; MR/M024962/1/MRC_/Medical Research Council/United Kingdom ; TURNER/OCT18/989-797/MNDA_/Motor Neurone Disease Association/United Kingdom ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics ; Matrix Metalloproteinase 9/genetics ; C9orf72 Protein/genetics ; Microglia ; Coculture Techniques ; *Induced Pluripotent Stem Cells ; Lipopolysaccharides ; *Neurodegenerative Diseases ; Motor Neurons ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive motor neuron loss, with additional pathophysiological involvement of non-neuronal cells such as microglia. The commonest ALS-associated genetic variant is a hexanucleotide repeat expansion (HRE) mutation in C9orf72. Here, we study its consequences for microglial function using human iPSC-derived microglia. By RNA-sequencing, we identify enrichment of pathways associated with immune cell activation and cyto-/chemokines in C9orf72 HRE mutant microglia versus healthy controls, most prominently after LPS priming. Specifically, LPS-primed C9orf72 HRE mutant microglia show consistently increased expression and release of matrix metalloproteinase-9 (MMP9). LPS-primed C9orf72 HRE mutant microglia are toxic to co-cultured healthy motor neurons, which is ameliorated by concomitant application of an MMP9 inhibitor. Finally, we identify release of dipeptidyl peptidase-4 (DPP4) as a marker for MMP9-dependent microglial dysregulation in co-culture. These results demonstrate cellular dysfunction of C9orf72 HRE mutant microglia, and a non-cell-autonomous role in driving C9orf72-ALS pathophysiology in motor neurons through MMP9 signaling.}, } @article {pmid37736625, year = {2023}, author = {Kvande, K and Garetto, B and Deplano, G and Signorile, M and Solemsli, BG and Prodinger, S and Olsbye, U and Beato, P and Bordiga, S and Svelle, S and Borfecchia, E}, title = {Understanding C-H activation in light alkanes over Cu-MOR zeolites by coupling advanced spectroscopy and temperature-programmed reduction experiments.}, journal = {Chemical science}, volume = {14}, number = {36}, pages = {9704-9723}, pmid = {37736625}, issn = {2041-6520}, abstract = {The direct activation of methane to methanol (MTM) proceeds through a chemical-looping process over Cu-oxo sites in zeolites. Herein, we extend the overall understanding of oxidation reactions over metal-oxo sites and C-H activation reactions by pinpointing the evolution of Cu species during reduction. To do so, a set of temperature-programmed reduction experiments were performed with CH4, C2H6, and CO. With a temperature ramp, the Cu reduction could be accelerated to detect changes in Cu speciation that are normally not detected due to the slow CH4 adsorption/interaction during MTM (∼200 °C). To follow the Cu-speciation with the three reductants, X-ray absorption spectroscopy (XAS), UV-vis and FT-IR spectroscopy were applied. Multivariate curve resolution alternating least-square (MCR-ALS) analysis was used to resolve the time-dependent concentration profiles of pure Cu components in the X-ray absorption near edge structure (XANES) spectra. Within the large datasets, as many as six different Cu[II] and Cu[I] components were found. Close correlations were found between the XANES-derived Cu[II] to Cu[I] reduction, CH4 consumption, and CO2 production. A reducibility-activity relationship was also observed for the Cu-MOR zeolites. Extended X-ray absorption fine structure (EXAFS) spectra for the pure Cu components were furthermore obtained with MCR-ALS analysis. With wavelet transform (WT) analysis of the EXAFS spectra, we were able to resolve the atomic speciation at different radial distances from Cu (up to about 4 Å). These results indicate that all the Cu[II] components consist of multimeric Cu[II]-oxo sites, albeit with different Cu-Cu distances.}, } @article {pmid37736067, year = {2023}, author = {Chambers, C and Lichten, L and Crook, A and Uhlmann, WR and Dratch, L}, title = {Incorporating Genetic Testing Into the Care of Patients With Amyotrophic Lateral Sclerosis/Frontotemporal Degeneration Spectrum Disorders.}, journal = {Neurology. Clinical practice}, volume = {13}, number = {5}, pages = {e200201}, pmid = {37736067}, issn = {2163-0402}, abstract = {PURPOSE OF REVIEW: Amyotrophic lateral sclerosis (ALS) and frontotemporal degeneration (FTD) spectrum disorders have a strong genetic component. Genetic counselors are a limited resource, and therefore, other providers must be prepared to integrate genetic testing into their practice.

RECENT FINDINGS: Recent ALS/FTD studies have demonstrated that lack of family history does not preclude a genetic etiology. The benefits of a genetic diagnosis have expanded to include the potential to treat; thus, genetic testing is increasingly recommended to be offered to all persons with ALS/FTD.

SUMMARY: Offering genetic testing to persons with ALS/FTD spectrum disorders should be part of routine clinical neurologic care. All genetic testing should include discussion about the medical and psychosocial implications of testing for the patient and family members. Neurologists should be prepared to facilitate this process and recognize when referral to a genetic counselor is indicated.}, } @article {pmid37735909, year = {2023}, author = {Irie, T and Sawa, M}, title = {CDC7 kinase inhibitors: a survey of recent patent literature (2017-2022).}, journal = {Expert opinion on therapeutic patents}, volume = {33}, number = {7-8}, pages = {493-501}, doi = {10.1080/13543776.2023.2262138}, pmid = {37735909}, issn = {1744-7674}, mesh = {Humans ; *Cell Cycle Proteins/metabolism ; Patents as Topic ; Protein Serine-Threonine Kinases ; DNA Replication ; *Neoplasms ; }, abstract = {INTRODUCTION: CDC7 is a serine/threonine kinase which plays an important role in DNA replication. Inhibition of CDC7 in cancer cells causes lethal S phase or M phase progression, whereas inhibition of CDC7 in normal cells does not cause cell death and only leads to cell cycle arrest at the DNA replication checkpoint. Therefore, CDC7 has been recognized as a potential target for novel therapeutic interventions in cancers.

AREAS COVERED: Patent literature claiming novel small molecule compounds inhibiting CDC7 disclosed from 2017 to 2022.

EXPERT OPINION: Despite the indisputable positive impact of CDC7 as a drug target, there have been reported only a handful of chemical scaffolds as CDC7 inhibitors. Several CDC7 inhibitors have been progressed into clinical trials for cancer treatments, but they did not result in satisfactory efficacies in those trials. One possible reason for the failure might be due to the dose-limiting toxicities, and some of the observed toxicities were thought to be not related to CDC7 inhibition, suggesting it should be important to identify novel chemical scaffolds to eliminate unwanted toxicities. Another important factor is the patient stratification that would enable greater response, and the identification of such predictive biomarkers should be the key to success for the development of CDC7 inhibitors.}, } @article {pmid37735683, year = {2023}, author = {Sołek, P and Czechowska, E and Sowa-Kućma, M and Stachowicz, K and Kaczka, P and Tabęcka-Łonczyńska, A}, title = {Elucidating the molecular mechanisms underlying the induction of autophagy by antidepressant-like substances in C57BL/6J mouse testis model upon LPS challenge.}, journal = {Cell communication and signaling : CCS}, volume = {21}, number = {1}, pages = {251}, pmid = {37735683}, issn = {1478-811X}, mesh = {Animals ; Male ; Mice ; Antidepressive Agents/pharmacology ; Autophagy ; *Lipopolysaccharides/pharmacology ; Mice, Inbred C57BL ; Testis ; }, abstract = {The treatment of depression with pharmaceuticals is associated with many adverse side effects, including male fertility problems. The precise mechanisms by which these agents affect testicular cells remain largely unknown, but they are believed to induce cellular stress, which is sensed by the endoplasmic reticulum (ER) and the Golgi apparatus. These organelles are responsible for maintaining cellular homeostasis and regulating signal pathways that lead to autophagy or apoptosis. Therefore, in this study, we aimed to investigate the autophagy, ER, and Golgi stress-related pathways in mouse testis following treatment with antidepressant-like substances (ALS) and ALS combined with lipopolysaccharide (LPS). We found that most ALS and activated proteins are associated with the induction of apoptosis. However, when imipramine (IMI) was combined with NS-398 (a cyclooxygenase-2 inhibitor) after LPS administration, we observed a marked increase in the BECLIN1, Bcl-2, ATG16L, and LC3 expression, which are marker proteins of autophagosome formation. The expression of the BECN1 and ATG16L genes was also high compared to the control, indicating the induction of autophagy processes that may potentially protect mouse testicular cells from death and regulate metabolism in the testis. Our findings may provide a better understanding of the stress-related effects of specific ALS on the testis. Video Abstract.}, } @article {pmid37735622, year = {2023}, author = {Sarkar, S and Elliott, EC and Henry, HR and Ludovico, ID and Melchior, JT and Frazer-Abel, A and Webb-Robertson, BJ and Davidson, WS and Holers, VM and Rewers, MJ and Metz, TO and Nakayasu, ES}, title = {Systematic review of type 1 diabetes biomarkers reveals regulation in circulating proteins related to complement, lipid metabolism, and immune response.}, journal = {Clinical proteomics}, volume = {20}, number = {1}, pages = {38}, pmid = {37735622}, issn = {1542-6416}, support = {P30 DK116073/DK/NIDDK NIH HHS/United States ; R01 DK032493/DK/NIDDK NIH HHS/United States ; U01 DK127505/DK/NIDDK NIH HHS/United States ; U01 DK127786/DK/NIDDK NIH HHS/United States ; }, abstract = {BACKGROUND: Type 1 diabetes (T1D) results from an autoimmune attack of the pancreatic β cells that progresses to dysglycemia and symptomatic hyperglycemia. Current biomarkers to track this evolution are limited, with development of islet autoantibodies marking the onset of autoimmunity and metabolic tests used to detect dysglycemia. Therefore, additional biomarkers are needed to better track disease initiation and progression. Multiple clinical studies have used proteomics to identify biomarker candidates. However, most of the studies were limited to the initial candidate identification, which needs to be further validated and have assays developed for clinical use. Here we curate these studies to help prioritize biomarker candidates for validation studies and to obtain a broader view of processes regulated during disease development.

METHODS: This systematic review was registered with Open Science Framework (https://doi.org/10.17605/OSF.IO/N8TSA). Using PRISMA guidelines, we conducted a systematic search of proteomics studies of T1D in the PubMed to identify putative protein biomarkers of the disease. Studies that performed mass spectrometry-based untargeted/targeted proteomic analysis of human serum/plasma of control, pre-seroconversion, post-seroconversion, and/or T1D-diagnosed subjects were included. For unbiased screening, 3 reviewers screened all the articles independently using the pre-determined criteria.

RESULTS: A total of 13 studies met our inclusion criteria, resulting in the identification of 266 unique proteins, with 31 (11.6%) being identified across 3 or more studies. The circulating protein biomarkers were found to be enriched in complement, lipid metabolism, and immune response pathways, all of which are found to be dysregulated in different phases of T1D development. We found 2 subsets: 17 proteins (C3, C1R, C8G, C4B, IBP2, IBP3, ITIH1, ITIH2, BTD, APOE, TETN, C1S, C6A3, SAA4, ALS, SEPP1 and PI16) and 3 proteins (C3, CLUS and C4A) have consistent regulation in at least 2 independent studies at post-seroconversion and post-diagnosis compared to controls, respectively, making them strong candidates for clinical assay development.

CONCLUSIONS: Biomarkers analyzed in this systematic review highlight alterations in specific biological processes in T1D, including complement, lipid metabolism, and immune response pathways, and may have potential for further use in the clinic as prognostic or diagnostic assays.}, } @article {pmid37735487, year = {2023}, author = {Gao, C and Jiang, J and Tan, Y and Chen, S}, title = {Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets.}, journal = {Signal transduction and targeted therapy}, volume = {8}, number = {1}, pages = {359}, pmid = {37735487}, issn = {2059-3635}, mesh = {Animals ; *Neurodegenerative Diseases/genetics ; Microglia ; Neuroinflammatory Diseases ; Protein Aggregates ; *Alzheimer Disease/genetics ; }, abstract = {Microglia activation is observed in various neurodegenerative diseases. Recent advances in single-cell technologies have revealed that these reactive microglia were with high spatial and temporal heterogeneity. Some identified microglia in specific states correlate with pathological hallmarks and are associated with specific functions. Microglia both exert protective function by phagocytosing and clearing pathological protein aggregates and play detrimental roles due to excessive uptake of protein aggregates, which would lead to microglial phagocytic ability impairment, neuroinflammation, and eventually neurodegeneration. In addition, peripheral immune cells infiltration shapes microglia into a pro-inflammatory phenotype and accelerates disease progression. Microglia also act as a mobile vehicle to propagate protein aggregates. Extracellular vesicles released from microglia and autophagy impairment in microglia all contribute to pathological progression and neurodegeneration. Thus, enhancing microglial phagocytosis, reducing microglial-mediated neuroinflammation, inhibiting microglial exosome synthesis and secretion, and promoting microglial conversion into a protective phenotype are considered to be promising strategies for the therapy of neurodegenerative diseases. Here we comprehensively review the biology of microglia and the roles of microglia in neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, multiple system atrophy, amyotrophic lateral sclerosis, frontotemporal dementia, progressive supranuclear palsy, corticobasal degeneration, dementia with Lewy bodies and Huntington's disease. We also summarize the possible microglia-targeted interventions and treatments against neurodegenerative diseases with preclinical and clinical evidence in cell experiments, animal studies, and clinical trials.}, } @article {pmid37735229, year = {2023}, author = {He, X and Yang, J and Feng, J and Huang, H and Dong, X and Zhao, Q and Shen, Q and Hu, C and Xu, Y}, title = {Venous blood parameters in determination of respiratory impairment in amyotrophic lateral sclerosis.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {15695}, pmid = {37735229}, issn = {2045-2322}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis ; *Respiratory Insufficiency ; Leukocyte Count ; Cholesterol, HDL ; Cholesterol, LDL ; Creatinine ; }, abstract = {This study aimed to investigate the relationship between venous blood parameters and respiratory functions in patients with amyotrophic lateral sclerosis (ALS) and develop a model to predict respiratory impairment for individual patients with ALS. A total of 416 ALS patients were included in the study, and various hematologic and biochemical laboratory parameters as well as demographic and clinical factors were collected and compared. A multivariable logistic regression model was constructed to assess the association between FVC and venous blood biomarkers and clinical factors. The results showed that along with onset age, bulbar-onset, disease duration, BMI, eosinophil count (EO#), basophil count (BASO#), creatinine (CREA), uric acid (URCI) and low-density lipoprotein cholesterol/high-density lipoprotein cholesterol (LDL/HDL) ratio were associated with reduced FVC. The area under the ROC curve is 0.735 for the test set and 0.721 for the validation set. The study also developed a relatively acceptable model for predicting respiratory impairment in ALS patients. These findings suggest that EO#, BASO#, CREA, URIC and LDL/HDL ratio can be useful in assessing FVC in ALS and can be easily accessible, accurate, and low-cost parameters.}, } @article {pmid37735015, year = {2023}, author = {Corcia, P and Vourc'h, P and Bernard, E and Cassereau, J and Codron, P and Fleury, MC and Guy, N and Mouzat, K and Pradat, PF and Soriani, MH and Couratier, P}, title = {French National Protocol for genetic of amyotrophic lateral sclerosis.}, journal = {Revue neurologique}, volume = {179}, number = {9}, pages = {1020-1029}, doi = {10.1016/j.neurol.2023.05.005}, pmid = {37735015}, issn = {0035-3787}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/epidemiology/genetics ; Mutation ; }, abstract = {Relationships between genes and amyotrophic lateral sclerosis (ALS) have been widely accepted since the first studies highlighting pathogenic mutations in the SOD1 gene 30years ago. Over the last three decades, scientific literature has clearly highlighted the central role played by genetic factors in the disease, in both clinics and pathophysiology, as well as in therapeutics. This implies that health professionals who care for patients with ALS are increasingly faced with patients and relatives eager to have answers to questions related to the role of genetic factors in the occurrence of the disease and the risk for their relatives to develop ALS. In order to address these public health issues, the French ALS network FILSLAN proposed to the Haute Autorité de santé (HAS) the drafting of a French National Protocol (PNDS) on ALS genetics. This PNDS was developed according to the "method for developing a national diagnosis and care protocol for rare diseases" published by the HAS in 2012 (methodological guide for PNDS available on the HAS website: http://www.has-sante.fr/). This document aims to provide the most recent data on the role of genes in ALS and to detail the implications for diagnosis and care.}, } @article {pmid37734916, year = {2023}, author = {Kredentser, MS and Mackenzie, CS and McClement, SE and Enns, MW and Hiebert-Murphy, D and Murphy, DJ and Chochinov, HM}, title = {Neuroticism as a moderator of symptom-related distress and depression in 4 noncancer end-of-life populations.}, journal = {Palliative & supportive care}, volume = {}, number = {}, pages = {1-9}, doi = {10.1017/S147895152300127X}, pmid = {37734916}, issn = {1478-9523}, abstract = {OBJECTIVES: Neuroticism is a significant predictor of adverse psychological outcomes in patients with cancer. Less is known about how this relationship manifests in those with noncancer illness at the end-of-life (EOL). The objective of this study was to examine the impact of neuroticism as a moderator of physical symptoms and development of depression in patients with amyotrophic lateral sclerosis (ALS), chronic obstructive pulmonary disease (COPD), end-stage renal disease (ESRD), and frailty in the last 6 months of life.

METHODS: We met this objective using secondary data collected in the Dignity and Distress across End-of-Life Populations study. The data included N = 404 patients with ALS (N = 101), COPD (N = 100), ESRD (N = 101), and frailty (N = 102) in the estimated last 6 months of life, with a range of illness-related symptoms, assessed longitudinally at 2 time points. We examined neuroticism as a moderator of illness-related symptoms at Time 1 (∼6 months before death) and depression at Time 2 (∼3 months before death) using ordinary least squares regression.

RESULTS: Results revealed that neuroticism significantly moderated the relationship between the following symptoms and depression measured 3 months later: drowsiness, fatigue, shortness of breath, wellbeing (ALS); drowsiness, trouble sleeping, will to live, activity (COPD); constipation (ESRD); and weakness and will to live (frailty).

SIGNIFICANCE OF RESULTS: These findings suggest that neuroticism represents a vulnerability factor that either attenuates or amplifies the relationship of specific illness and depressive symptoms in these noncancer illness groups at the EOL. Identifying those high in neuroticism may provide insight into patient populations that require special care at the EOL.}, } @article {pmid37734449, year = {2023}, author = {Hayashi, K and Sasaki, K}, title = {Number of kinesins engaged in axonal cargo transport: A novel biomarker for neurological disorders.}, journal = {Neuroscience research}, volume = {197}, number = {}, pages = {25-30}, doi = {10.1016/j.neures.2023.09.004}, pmid = {37734449}, issn = {1872-8111}, mesh = {Humans ; *Kinesins/metabolism ; Axonal Transport/physiology ; Axons/metabolism ; Dyneins/metabolism ; *Amyotrophic Lateral Sclerosis/metabolism ; }, abstract = {Kinesin motor proteins play crucial roles in anterograde transport of cargo vesicles in neurons, moving them along axons from the cell body towards the synaptic region. Not only the transport force and velocity of single motor protein, but also the number of kinesin molecules involved in transporting a specific cargo, is pivotal for synapse formation. This collective transport by multiple kinesins ensures stable and efficient cargo transport in neurons. Abnormal increases or decreases in the number of engaged kinesin molecules per cargo could potentially act as biomarkers for neurodegenerative diseases such as Alzheimer's, Parkinson's, amyotrophic lateral sclerosis (ALS), spastic paraplegia, polydactyly syndrome, and virus transport disorders. We review here a model constructed using physical measurements to quantify the number of kinesin molecules associated with their cargo, which could shed light on the molecular mechanisms of neurodegenerative diseases related to axonal transport.}, } @article {pmid37734132, year = {2023}, author = {Cengiz, B and Koçak, ÖK and Erdoğan, T and Yanık, E and Pek, G and Savrun, Y and Evren Boran, H and Reha Kuruoğlu, H}, title = {Excitability of somatosensory cortex is increased in ALS: A SEP recovery function study.}, journal = {Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology}, volume = {155}, number = {}, pages = {58-64}, doi = {10.1016/j.clinph.2023.08.013}, pmid = {37734132}, issn = {1872-8952}, abstract = {OBJECTIVE: Neuronal loss in the somatosensory, as well as the motor cortex in amyotrophic lateral sclerosis (ALS), indicative of a structural abnormality has been reported. Previously we have shown that afferent inhibition was impaired in ALS, suggestive of sensory involvement. In this study, we aimed to evaluate excitability changes in the somatosensory cortex of ALS patients.

METHODS: ALS patients underwent a paired pulse somatosensory evoked potential (SEP) paradigm at various interstimulus intervals (ISI). The amplitude ratio obtained by dividing the amplitude of paired pulse SEP stimulation S2 (paired pulse stimulation) to S1 (the single pulse stimulation) was considered the somatosensory cortex excitability parameter. Findings were compared to the results obtained from healthy controls. Resting motor threshold (RMT) was also assessed in the ALS group.

RESULTS: An increased S2/S1 ratio was found in the ALS group in every ISI examined. Additionally, the reduced inhibition correlated negatively with forced vital capacity, Medical Research Council sum score, median nerve compound muscle action potential amplitude, while there was a positive association with Penn upper motor neuron score and sural nerve conduction velocity. No correlation existed with RMT.

CONCLUSIONS: Our findings demonstrated increased somatosensory cortical excitability in ALS, which was associated with clinical parameters such as reduced pulmonary function and motor strength.

SIGNIFICANCE: Somatosensory cortical excitability is impaired in ALS. Whether this is associated with increased motor cortical excitability requires further studies.}, } @article {pmid37733208, year = {2023}, author = {Hernández, S and Salvany, S and Casanovas, A and Piedrafita, L and Soto-Bernardini, MC and Tarabal, O and Blasco, A and Gras, S and Gatius, A and Schwab, MH and Calderó, J and Esquerda, JE}, title = {Persistent NRG1 Type III Overexpression in Spinal Motor Neurons Has No Therapeutic Effect on ALS-Related Pathology in SOD1[G93A] Mice.}, journal = {Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics}, volume = {20}, number = {6}, pages = {1820-1834}, pmid = {37733208}, issn = {1878-7479}, support = {PID2021-122785OB-I00//Ministerio de Ciencia, Innovación y Universidades/ ; 202005-30//Fundació la Marató de TV3/ ; }, mesh = {Animals ; Mice ; *Amyotrophic Lateral Sclerosis/genetics/therapy/metabolism ; Mice, Transgenic ; Motor Neurons/pathology ; Neuregulin-1/genetics ; *Neurodegenerative Diseases/metabolism ; Superoxide Dismutase/genetics/metabolism ; Superoxide Dismutase-1/genetics ; Disease Models, Animal ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease affecting upper and lower motor neurons (MNs). Neuregulin-1 (NRG1) is a pleiotropic growth factor that has been shown to be potentially valuable for ALS when supplemented by means of viral-mediated gene therapy. However, these results are inconsistent with other reports. An alternative approach for investigating the therapeutic impact of NRG1 on ALS is the use of transgenic mouse lines with genetically defined NRG1 overexpression. Here, we took advantage of a mouse line with NRG1 type III overexpression in spinal cord α motor neurons (MN) to determine the impact of steadily enhanced NRG1 signalling on mutant superoxide dismutase 1 (SOD1)-induced disease. The phenotype of SOD1[G93A]-NRG1 double transgenic mice was analysed in detail, including neuropathology and extensive behavioural testing. At least 3 animals per condition and sex were histopathologically assessed, and a minimum of 10 mice per condition and sex were clinically evaluated. The accumulation of misfolded SOD1 (mfSOD1), MN degeneration, and a glia-mediated neuroinflammatory response are pathological hallmarks of ALS progression in SOD1[G93A] mice. None of these aspects was significantly improved when examined in double transgenic NRG1-SOD1[G93A] mice. In addition, behavioural testing revealed that NRG1 type III overexpression did not affect the survival of SOD1[G93A] mice but accelerated disease onset and worsened the motor phenotype.}, } @article {pmid37732211, year = {2023}, author = {Guo, L and Mann, JR and Mauna, JC and Copley, KE and Wang, H and Rubien, JD and Odeh, HM and Lin, J and Lee, BL and Ganser, L and Robinson, E and Kim, KM and Murthy, AC and Paul, T and Portz, B and Gleixner, AM and Diaz, Z and Carey, JL and Smirnov, A and Padilla, G and Lavorando, E and Espy, C and Shang, Y and Huang, EJ and Chesi, A and Fawzi, NL and Myong, S and Donnelly, CJ and Shorter, J}, title = {Defining RNA oligonucleotides that reverse deleterious phase transitions of RNA-binding proteins with prion-like domains.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2023.09.04.555754}, pmid = {37732211}, issn = {2692-8205}, support = {F31 NS129101/NS/NINDS NIH HHS/United States ; R01 NS121143/NS/NINDS NIH HHS/United States ; R35 GM138109/GM/NIGMS NIH HHS/United States ; RF1 NS121143/NS/NINDS NIH HHS/United States ; }, abstract = {RNA-binding proteins with prion-like domains, such as FUS and TDP-43, condense into functional liquids, which can transform into pathological fibrils that underpin fatal neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS)/frontotemporal dementia (FTD). Here, we define short RNAs (24-48 nucleotides) that prevent FUS fibrillization by promoting liquid phases, and distinct short RNAs that prevent and, remarkably, reverse FUS condensation and fibrillization. These activities require interactions with multiple RNA-binding domains of FUS and are encoded by RNA sequence, length, and structure. Importantly, we define a short RNA that dissolves aberrant cytoplasmic FUS condensates, restores nuclear FUS, and mitigates FUS proteotoxicity in optogenetic models and human motor neurons. Another short RNA dissolves aberrant cytoplasmic TDP-43 condensates, restores nuclear TDP-43, and mitigates TDP-43 proteotoxicity. Since short RNAs can be effectively delivered to the human brain, these oligonucleotides could have therapeutic utility for ALS/FTD and related disorders.}, } @article {pmid37730935, year = {2024}, author = {Ferrari, C and Ingannato, A and Matà, S and Ramat, S and Caremani, L and Bagnoli, S and Bessi, V and Sorbi, S and Nacmias, B}, title = {Parkinson-ALS with a novel MAPT variant.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {45}, number = {3}, pages = {1051-1055}, pmid = {37730935}, issn = {1590-3478}, mesh = {Female ; Humans ; Middle Aged ; *Amyotrophic Lateral Sclerosis/genetics ; *Frontotemporal Dementia/genetics/pathology ; tau Proteins/genetics ; *Parkinson Disease/genetics ; Mutation/genetics ; *Parkinsonian Disorders/genetics ; }, abstract = {The mutations on microtubule associated protein tau (MAPT) gene manifest clinically with behavioural frontotemporal dementia (FTD), parkinsonism, such as progressive supranuclear palsy and corticobasal degeneration, and rarely with amyotrophic lateral sclerosis (ALS). FTD-parkinsonism and FTD-ALS are clinical overlaps included in the spectrum of MAPT mutation's phenotypes. The mutations on MAPT gene cause the dysfunction of tau protein determining its accumulation in neurofibrillary tangles. Recent data describe frequently the co-occurrence of the aggregation of tau protein and α-synuclein in patients with parkinsonism and Parkinson disease (PD), suggesting an interaction of the two proteins in determining neurodegenerative process. The sporadic description of PD-ALS clinical complex, known as Brait-Fahn-Schwarz disease, supports the hypothesis of common neuropathological pathways between different disorders. Here we report the case of a 54-year-old Italian woman with idiopathic PD later complicated by ALS carrying a novel MAPT variant (Pro494Leu). The variant is characterized by an amino acid substitution and is classified as damaging for MAPT functions. The case supports the hypothesis of tau dysfunction as the basis of multiple neurodegenerative disorders.}, } @article {pmid37730668, year = {2023}, author = {Zhu, L and Li, S and Li, XJ and Yin, P}, title = {Pathological insights from amyotrophic lateral sclerosis animal models: comparisons, limitations, and challenges.}, journal = {Translational neurodegeneration}, volume = {12}, number = {1}, pages = {46}, pmid = {37730668}, issn = {2047-9158}, mesh = {Humans ; Animals ; Swine ; *Amyotrophic Lateral Sclerosis/genetics ; *Neurodegenerative Diseases ; Brain ; }, abstract = {In order to dissect amyotrophic lateral sclerosis (ALS), a multigenic, multifactorial, and progressive neurodegenerative disease with heterogeneous clinical presentations, researchers have generated numerous animal models to mimic the genetic defects. Concurrent and comparative analysis of these various models allows identification of the causes and mechanisms of ALS in order to finally obtain effective therapeutics. However, most genetically modified rodent models lack overt pathological features, imposing challenges and limitations in utilizing them to rigorously test the potential mechanisms. Recent studies using large animals, including pigs and non-human primates, have uncovered important events that resemble neurodegeneration in patients' brains but could not be produced in small animals. Here we describe common features as well as discrepancies among these models, highlighting new insights from these models. Furthermore, we will discuss how to make rodent models more capable of recapitulating important pathological features based on the important pathogenic insights from large animal models.}, } @article {pmid37729728, year = {2023}, author = {Anzilotti, S and Valente, V and Brancaccio, P and Franco, C and Casamassa, A and Lombardi, G and Palazzi, A and Conte, A and Paladino, S and Canzoniero, LMT and Annunziato, L and Pierantoni, GM and Pignataro, G}, title = {Chronic exposure to l-BMAA cyanotoxin induces cytoplasmic TDP-43 accumulation and glial activation, reproducing an amyotrophic lateral sclerosis-like phenotype in mice.}, journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie}, volume = {167}, number = {}, pages = {115503}, doi = {10.1016/j.biopha.2023.115503}, pmid = {37729728}, issn = {1950-6007}, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive and often fatal neurodegenerative disease characterized by the loss of Motor Neurons (MNs) in spinal cord, motor cortex and brainstem. Despite significant efforts in the field, the exact pathogenetic mechanisms underlying both familial and sporadic forms of ALS have not been fully elucidated, and the therapeutic possibilities are still very limited. Here we investigate the molecular mechanisms of neurodegeneration induced by chronic exposure to the environmental cyanotoxin L-BMAA, which causes a form of ALS/Parkinson's disease (PD) in several populations consuming food and/or water containing high amounts of this compound.

METHODS: In this effort, mice were chronically exposed to L-BMAA and analyzed at different time points to evaluate cellular and molecular alterations and behavioral deficits, performing MTT assay, immunoblot, immunofluorescence and immunohistochemistry analysis, and behavioral tests.

RESULTS: We found that cyanotoxin L-BMAA determines apoptotic cell death and a marked astrogliosis in spinal cord and motor cortex, and induces neurotoxicity by favoring TDP-43 cytoplasmic accumulation.

CONCLUSIONS: Overall, our results characterize a new versatile neurotoxic animal model of ALS that may be useful for the identification of new druggable targets to develop innovative therapeutic strategies for this disease.}, } @article {pmid37728482, year = {2023}, author = {Keun, CH and Choi, SJ and Kim, YJ and Kim, SM and Hong, YH and Sung, JJ}, title = {Suicide Attempts in Patients With Amyotrophic Lateral Sclerosis: An Analysis of the Korean National Health Insurance Database.}, journal = {The Journal of clinical psychiatry}, volume = {84}, number = {6}, pages = {}, doi = {10.4088/JCP.22m14754}, pmid = {37728482}, issn = {1555-2101}, mesh = {Humans ; *Suicide, Attempted ; *Amyotrophic Lateral Sclerosis/epidemiology ; Cohort Studies ; National Health Programs ; Republic of Korea/epidemiology ; }, abstract = {Objective: The knowledge of the common risk factors for suicide attempts may not be simply applicable to patients with amyotrophic lateral sclerosis (ALS). We aimed to identify risk factors associated with suicide attempts in patients with ALS and to determine the annual prevalence and periods of vulnerability associated with attempts. Methods: This nationwide cohort study was performed using the Korean National Health Insurance Database. All patients with ALS concomitantly registered for the Exempted Calculation of Health Insurance for rare, incurable diseases between 2011 and 2017 were identified. We used the Cox proportional hazards regression model and competing risk model to identify the risk factors for suicide attempts. The multivariable models were adjusted for potential risk factors from the univariate analysis. Results: Among 2,955 incident patients, 47 attempted suicide. After adjusting for sex, previous attempts, and previous psychiatric disorders, the hazard ratios for psychiatric hospitalization before ALS diagnosis were 3.17 (95% confidence interval [CI], 1.31-7.70; P = .01) and 3.02 (95% CI, 1.32-6.90; P = .01) in the Cox regression model and the competing risk model, respectively. The annual prevalence of suicide attempts was 0.29%-1.12%. Twenty (42.6%) and 9 (19.1%) attempts occurred within 3 months and 12-18 months after diagnosis, respectively. Conclusions: Psychiatric hospitalization increased the risk of suicide attempts, which clustered at the early stage or on losing autonomy. Those with a history of psychiatric hospitalization should receive an in-depth evaluation and be cautiously monitored.}, } @article {pmid37728307, year = {2024}, author = {Shefner, JM and Bunte, T and Kittle, G and Genge, A and van den Berg, LH}, title = {Harmonized standard operating procedures for administering the ALS functional rating scale-revised.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {25}, number = {1-2}, pages = {26-33}, doi = {10.1080/21678421.2023.2260832}, pmid = {37728307}, issn = {2167-9223}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis ; Outcome Assessment, Health Care ; Europe ; }, abstract = {The ALS Functional Rating Scale-Revised is the most commonly used primary outcome measure in current ALS clinical trials. While rigorous training and certification is generally recognized as critical to reliable performance, differences have existed between training in the two groups responsible for most training in ALS outcome measures. We present a harmonized standard operating procedure which is intended to further reduce response variability by the use of identical training in North America and Europe.}, } @article {pmid37725936, year = {2024}, author = {Giannakopoulos, A and Papanastasiou, AD and Zarkadis, IK and Andrew, SF and Rosenfeld, RG and Efthymiadou, A and Chrysis, D and Hwa, V}, title = {A Novel, Heterozygous, de novo Splicing Variant Affecting the Intracellular Domain of the Growth Hormone Receptor, and Causing a Mild Short Stature.}, journal = {Hormone research in paediatrics}, volume = {97}, number = {4}, pages = {397-403}, doi = {10.1159/000534183}, pmid = {37725936}, issn = {1663-2826}, mesh = {Humans ; Male ; Adolescent ; *Receptors, Somatotropin/genetics ; Heterozygote ; RNA Splicing ; Laron Syndrome/genetics ; Protein Domains ; Dwarfism/genetics ; Mutation ; Body Height/genetics ; }, abstract = {INTRODUCTION: Although the majority of growth hormone insensitivity syndrome (GHIS) cases are classical, the spectrum of clinical phenotypes has expanded to include "atypical" GHIS subjects with milder phenotypes due to very rare heterozygous growth hormone receptor (GHR) mutations with dominant negative effects.

CASE PRESENTATION: A 13-year-old pubertal boy presented with short stature (-1.7 SDS) and delayed bone age (11.5 years). His serum IGF-1 was low (16 ng/mL; reference range: 179-540). IGFBP-3 (1.3 mg/L; 3.1-9.5) and ALS (565 mU/mL; 1,500-3,500) were also low. GH stimulation test was normal, and GHBP was markedly elevated (6,300 pmol/L; 240-3,000). Additionally, the boy had insulin resistance and liver steatosis. His final height reached -1.8 SDS, which was 3.0 SDS below his mid-parental height. GHR gene from genomic DNA and established primary fibroblast culture was analyzed and a synonymous heterozygous GHR: c.945G>A variant, in the last nucleotide of exon 9 (encoding intracellular domain of GHR) was identified. In vitro analysis of the GHR cDNA demonstrated a splicing defect, leading to the heterozygous excision of exon 9. The final predicted product was a truncated GHR protein which explained the elevated GHBP levels.

CONCLUSION: We describe the first synonymous heterozygous GHR splicing variant in the exon 9-encoding part of the intracellular domain of GHR identified in a patient with mild short stature, thus supporting the continuum of genotype-phenotype of GHIS.}, } @article {pmid37725878, year = {2023}, author = {Singh, N and Vishwas, S and Kaur, A and Kaur, H and Kakoty, V and Khursheed, R and Chaitanya, MVNL and Babu, MR and Awasthi, A and Corrie, L and Harish, V and Yanadaiah, P and Gupta, S and Sayed, AA and El-Sayed, A and Ali, I and Kensara, OA and Ghaboura, N and Gupta, G and Dou, AM and Algahtani, M and El-Kott, AF and Dua, K and Singh, SK and Abdel-Daim, MM}, title = {Harnessing role of sesamol and its nanoformulations against neurodegenerative diseases.}, journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie}, volume = {167}, number = {}, pages = {115512}, doi = {10.1016/j.biopha.2023.115512}, pmid = {37725878}, issn = {1950-6007}, abstract = {Sesamol is a lignan of sesame seeds and a natural phenolic molecule that has emerged as a useful medical agent. Sesamol is a non-toxic phytoconstituent, which exerts certain valuable effects in the management of cancer, diabetes, cardiovascular diseases, neurodegenerative diseases (NDs), etc. Sesamol is known to depict its neuroprotective role by various mechanisms, such as metabolic regulators, action on oxidative stress, neuroinflammation, etc. However, its poor oral bioavailability, rapid excretion (as conjugates), and susceptibility to gastric irritation/toxicity (particularly in rats' forestomach) may restrict its effectiveness. To overcome the associated limitations, novel drug delivery system-based formulations of sesamol are emerging and being researched extensively. These can conjugate with sesamol and enhance the bioavailability and solubility of free sesamol, along with delivery at the target site. In this review, we have summarized various research works highlighting the role of sesamol on various NDs, including Alzheimer's disease, Huntington's disease, Amyotrophic lateral sclerosis, and Parkinson's disease. Moreover, the formulation strategies and neuroprotective role of sesamol-based nano-formulations have also been discussed.}, } @article {pmid37725216, year = {2024}, author = {Dar, NJ and John, U and Bano, N and Khan, S and Bhat, SA}, title = {Oxytosis/Ferroptosis in Neurodegeneration: the Underlying Role of Master Regulator Glutathione Peroxidase 4 (GPX4).}, journal = {Molecular neurobiology}, volume = {61}, number = {3}, pages = {1507-1526}, pmid = {37725216}, issn = {1559-1182}, mesh = {Humans ; Phospholipid Hydroperoxide Glutathione Peroxidase/metabolism ; *Ferroptosis ; Cell Death ; Oxidation-Reduction ; *Neurodegenerative Diseases ; Glutathione Peroxidase/metabolism ; Glutathione/metabolism ; Lipid Peroxidation ; }, abstract = {Oxytosis/ferroptosis is an iron-dependent oxidative form of cell death triggered by lethal accumulation of phospholipid hydroperoxides (PLOOHs) in membranes. Failure of the intricate PLOOH repair system is a principle cause of ferroptotic cell death. Glutathione peroxidase 4 (GPX4) is distinctly vital for converting PLOOHs in membranes to non-toxic alcohols. As such, GPX4 is known as the master regulator of oxytosis/ferroptosis. Ferroptosis has been implicated in a number of disorders such as neurodegenerative diseases (amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD), etc.), ischemia/reperfusion injury, and kidney degeneration. Reduced function of GPX4 is frequently observed in degenerative disorders. In this study, we examine how diminished GPX4 function may be a critical event in triggering oxytosis/ferroptosis to perpetuate or initiate the neurodegenerative diseases and assess the possible therapeutic importance of oxytosis/ferroptosis in neurodegenerative disorders. These discoveries are important for advancing our understanding of neurodegenerative diseases because oxytosis/ferroptosis may provide a new target to slow the course of the disease.}, } @article {pmid37723585, year = {2023}, author = {Beckers, J and Tharkeshwar, AK and Fumagalli, L and Contardo, M and Van Schoor, E and Fazal, R and Thal, DR and Chandran, S and Mancuso, R and Van Den Bosch, L and Van Damme, P}, title = {A toxic gain-of-function mechanism in C9orf72 ALS impairs the autophagy-lysosome pathway in neurons.}, journal = {Acta neuropathologica communications}, volume = {11}, number = {1}, pages = {151}, pmid = {37723585}, issn = {2051-5960}, support = {MR/N013255/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics ; C9orf72 Protein/genetics ; Gain of Function Mutation ; Lysosomes ; Motor Neurons ; Autophagy ; }, abstract = {BACKGROUND: Motor neurons (MNs), which are primarily affected in amyotrophic lateral sclerosis (ALS), are a specialized type of neurons that are long and non-dividing. Given their unique structure, these cells heavily rely on transport of organelles along their axons and the process of autophagy to maintain their cellular homeostasis. It has been shown that disruption of the autophagy pathway is sufficient to cause progressive neurodegeneration and defects in autophagy have been associated with various subtypes of ALS, including those caused by hexanucleotide repeat expansions in the C9orf72 gene. A more comprehensive understanding of the dysfunctional cellular mechanisms will help rationalize the design of potent and selective therapies for C9orf72-ALS.

METHODS: In this study, we used induced pluripotent stem cell (iPSC)-derived MNs from C9orf72-ALS patients and isogenic control lines to identify the underlying mechanisms causing dysregulations of the autophagy-lysosome pathway. Additionally, to ascertain the potential impact of C9orf72 loss-of-function on autophagic defects, we characterized the observed phenotypes in a C9orf72 knockout iPSC line (C9-KO).

RESULTS: Despite the evident presence of dysfunctions in several aspects of the autophagy-lysosome pathway, such as disrupted lysosomal homeostasis, abnormal lysosome morphology, inhibition of autophagic flux, and accumulation of p62 in C9orf72-ALS MNs, we were surprised to find that C9orf72 loss-of-function had minimal influence on these phenotypes. Instead, we primarily observed impairment in endosome maturation as a result of C9orf72 loss-of-function. Additionally, our study shed light on the pathological mechanisms underlying C9orf72-ALS, as we detected an increased TBK1 phosphorylation at S172 in MNs derived from C9orf72 ALS patients.

CONCLUSIONS: Our data provides further insight into the involvement of defects in the autophagy-lysosome pathway in C9orf72-ALS and strongly indicate that those defects are mainly due to the toxic gain-of-function mechanisms underlying C9orf72-ALS.}, } @article {pmid37723203, year = {2023}, author = {Huang, X and Jia, H and Xu, J and Wang, Y and Wen, J and Wang, N}, title = {Transgene-free genome editing of vegetatively propagated and perennial plant species in the T0 generation via a co-editing strategy.}, journal = {Nature plants}, volume = {9}, number = {10}, pages = {1591-1597}, pmid = {37723203}, issn = {2055-0278}, support = {2022-70029-38471//US Department of Agriculture/ ; 2021-67013-34588//US Department of Agriculture/ ; 2018-70016-27412//US Department of Agriculture/ ; 2016-70016-24833//US Department of Agriculture/ ; FLA-CRC-005979//Florida Department of Agriculture and Consumer Services/ ; }, mesh = {*Gene Editing ; CRISPR-Cas Systems ; Transgenes ; Plants, Genetically Modified/genetics ; *Herbicides ; Genome, Plant ; }, abstract = {Transgene-free plant genome editing in the T0 generation is highly desirable but challenging[1,2]. Here we achieved such a goal using a co-editing strategy via Agrobacterium-mediated transient expression of cytosine base editor to edit ALS encoding acetolactate synthase to confer herbicide chlorsulfuron resistance as a selection marker, Cas12a/CRISPR RNA for editing gene(s) of interest, and green fluorescent protein for selecting transgene-free transformants. The biallelic/homozygous transgene-free mutation rates for target genes among herbicide-resistant transformants ranged from 1.9% to 42.1% in tomato, tobacco, potato and citrus. This co-editing strategy is particularly useful for transgene-free genome editing of vegetatively propagated and perennial plant species in the T0 generation.}, } @article {pmid37722062, year = {2023}, author = {Chi, B and Öztürk, MM and Paraggio, CL and Leonard, CE and Sanita, ME and Dastpak, M and O'Connell, JD and Coady, JA and Zhang, J and Gygi, SP and Lopez-Gonzalez, R and Yin, S and Reed, R}, title = {Causal ALS genes impact the MHC class II antigen presentation pathway.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {120}, number = {39}, pages = {e2305756120}, pmid = {37722062}, issn = {1091-6490}, support = {R01 GM067945/GM/NIGMS NIH HHS/United States ; R35 GM122524/GM/NIGMS NIH HHS/United States ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics ; Antigen Presentation/genetics ; Genes, MHC Class II ; Major Histocompatibility Complex ; Motor Neurons ; RNA-Binding Proteins/genetics ; Nuclear Matrix-Associated Proteins ; }, abstract = {Mutations in RNA/DNA-binding proteins cause amyotrophic lateral sclerosis (ALS), but the underlying disease mechanisms remain unclear. Here, we report that a set of ALS-associated proteins, namely FUS, EWSR1, TAF15, and MATR3, impact the expression of genes encoding the major histocompatibility complex II (MHC II) antigen presentation pathway. Both subunits of the MHC II heterodimer, HLA-DR, are down-regulated in ALS gene knockouts/knockdown in HeLa and human microglial cells, due to loss of the MHC II transcription factor CIITA. Importantly, hematopoietic progenitor cells (HPCs) derived from human embryonic stem cells bearing the FUS[R495X] mutation and HPCs derived from C9ORF72 ALS patient induced pluripotent stem cells also exhibit disrupted MHC II expression. Given that HPCs give rise to numerous immune cells, our data raise the possibility that loss of the MHC II pathway results in global failure of the immune system to protect motor neurons from damage that leads to ALS.}, } @article {pmid37721281, year = {2024}, author = {Jourdi, G and Fleury, S and Boukhatem, I and Lordkipanidzé, M}, title = {Soluble p75 neurotrophic receptor as a reliable biomarker in neurodegenerative diseases: what is the evidence?.}, journal = {Neural regeneration research}, volume = {19}, number = {3}, pages = {536-541}, pmid = {37721281}, issn = {1673-5374}, abstract = {Neurodegenerative diseases are often misdiagnosed, especially when the diagnosis is based solely on clinical symptoms. The p75 neurotrophic receptor (p75[NTR]) has been studied as an index of sensory and motor nerve development and maturation. Its cleavable extracellular domain (ECD) is readily detectable in various biological fluids including plasma, serum and urine. There is evidence for increased p75[NTR] ECD levels in neurodegenerative diseases such as Alzheimer's disease, amyotrophic lateral sclerosis, age-related dementia, schizophrenia, and diabetic neuropathy. Whether p75[NTR] ECD could be used as a biomarker for diagnosis and/or prognosis in these disorders, and whether it could potentially lead to the development of targeted therapies, remains an open question. In this review, we present and discuss published studies that have evaluated the relevance of this emerging biomarker in the context of various neurodegenerative diseases. We also highlight areas that require further investigation to better understand the role of p75[NTR] ECD in the clinical diagnosis and management of neurodegenerative disorders.}, } @article {pmid37721161, year = {2024}, author = {Guo, K and Figueroa-Romero, C and Noureldein, MH and Murdock, BJ and Savelieff, MG and Hur, J and Goutman, SA and Feldman, EL}, title = {Gut microbiome correlates with plasma lipids in amyotrophic lateral sclerosis.}, journal = {Brain : a journal of neurology}, volume = {147}, number = {2}, pages = {665-679}, pmid = {37721161}, issn = {1460-2156}, support = {UL1TR002240/NH/NIH HHS/United States ; K23 ES027221/ES/NIEHS NIH HHS/United States ; R01TS000339/ACL/ACL HHS/United States ; R01 ES030049/ES/NIEHS NIH HHS/United States ; UL1 TR002240/TR/NCATS NIH HHS/United States ; R01 TS000339/TS/ATSDR CDC HHS/United States ; R01 NS127188/NS/NINDS NIH HHS/United States ; /CC/CDC HHS/United States ; UL1 TR000433/TR/NCATS NIH HHS/United States ; UM1 TR004404/TR/NCATS NIH HHS/United States ; R01 TS000289/TS/ATSDR CDC HHS/United States ; R01TS000289/ACL/ACL HHS/United States ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics ; *Gastrointestinal Microbiome/genetics ; *Neurodegenerative Diseases ; Biomarkers ; Lipids ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a complex, fatal neurodegenerative disease. Disease pathophysiology is incompletely understood but evidence suggests gut dysbiosis occurs in ALS, linked to impaired gastrointestinal integrity, immune system dysregulation and altered metabolism. Gut microbiome and plasma metabolome have been separately investigated in ALS, but little is known about gut microbe-plasma metabolite correlations, which could identify robust disease biomarkers and potentially shed mechanistic insight. Here, gut microbiome changes were longitudinally profiled in ALS and correlated to plasma metabolome. Gut microbial structure at the phylum level differed in ALS versus control participants, with differential abundance of several distinct genera. Unsupervised clustering of microbe and metabolite levels identified modules, which differed significantly in ALS versus control participants. Network analysis found several prominent amplicon sequence variants strongly linked to a group of metabolites, primarily lipids. Similarly, identifying the features that contributed most to case versus control separation pinpointed several bacteria correlated to metabolites, predominantly lipids. Mendelian randomization indicated possible causality from specific lipids related to fatty acid and acylcarnitine metabolism. Overall, the results suggest ALS cases and controls differ in their gut microbiome, which correlates with plasma metabolites, particularly lipids, through specific genera. These findings have the potential to identify robust disease biomarkers and shed mechanistic insight into ALS.}, } @article {pmid37721118, year = {2024}, author = {Gao, J and Jiang, M and Erricolo, D and Magin, RL and Morfini, G and Royston, T and Larson, AC and Li, W}, title = {Identifying potential imaging markers for diffusion property changes in a mouse model of amyotrophic lateral sclerosis: Application of the continuous time random walk model to ultrahigh b-value diffusion-weighted MR images of spinal cord tissue.}, journal = {NMR in biomedicine}, volume = {37}, number = {1}, pages = {e5037}, doi = {10.1002/nbm.5037}, pmid = {37721118}, issn = {1099-1492}, support = {RO1CA181658/GF/NIH HHS/United States ; }, mesh = {Mice ; Animals ; *Amyotrophic Lateral Sclerosis/diagnostic imaging/pathology ; Superoxide Dismutase-1 ; Spinal Cord/diagnostic imaging/pathology ; Mice, Transgenic ; Diffusion Magnetic Resonance Imaging ; Disease Models, Animal ; }, abstract = {Diffusion MRI (dMRI) explores tissue microstructures by analyzing diffusion-weighted signal decay measured at different b-values. While relatively low b-values are used for most dMRI models, high b-value diffusion-weighted imaging (DWI) techniques have gained interest given that the non-Gaussian water diffusion behavior observed at high b-values can yield potentially valuable information. In this study, we investigated anomalous diffusion behaviors associated with degeneration of spinal cord tissue using a continuous time random walk (CTRW) model for DWI data acquired across an extensive range of ultrahigh b-values. The diffusion data were acquired in situ from the lumbar level of spinal cords of wild-type and age-matched transgenic SOD1[G93A] mice, a well-established animal model of amyotrophic lateral sclerosis (ALS) featuring progressive degeneration of axonal tracts in this tissue. Based on the diffusion decay behaviors at low and ultrahigh b-values, we applied the CTRW model using various combinations of b-values and compared diffusion metrics calculated from the CTRW model between the experimental groups. We found that diffusion-weighted signal decay curves measured with ultrahigh b-values (up to 858,022 s/mm[2] in this study) were well represented by the CTRW model. The anomalous diffusion coefficient obtained from lumbar spinal cords was significantly higher in SOD1[G93A] mice compared with control mice (14.7 × 10[-5] ± 5.54 × 10[-5] vs. 7.87 × 10[-5] ± 2.48 × 10[-5] mm[2] /s, p = 0.01). We believe this is the first study to illustrate the efficacy of the CTRW model for analyzing anomalous diffusion regimes at ultrahigh b-values. The CTRW modeling of ultrahigh b-value dMRI can potentially present a novel approach for noninvasively evaluating alterations in spinal cord tissue associated with ALS pathology.}, } @article {pmid37720552, year = {2023}, author = {Naskar, A and Nayak, A and Salaikumaran, MR and Vishal, SS and Gopal, PP}, title = {Phase separation and pathologic transitions of RNP condensates in neurons: implications for amyotrophic lateral sclerosis, frontotemporal dementia and other neurodegenerative disorders.}, journal = {Frontiers in molecular neuroscience}, volume = {16}, number = {}, pages = {1242925}, pmid = {37720552}, issn = {1662-5099}, support = {R01 NS122907/NS/NINDS NIH HHS/United States ; }, abstract = {Liquid-liquid phase separation results in the formation of dynamic biomolecular condensates, also known as membrane-less organelles, that allow for the assembly of functional compartments and higher order structures within cells. Multivalent, reversible interactions between RNA-binding proteins (RBPs), including FUS, TDP-43, and hnRNPA1, and/or RNA (e.g., RBP-RBP, RBP-RNA, RNA-RNA), result in the formation of ribonucleoprotein (RNP) condensates, which are critical for RNA processing, mRNA transport, stability, stress granule assembly, and translation. Stress granules, neuronal transport granules, and processing bodies are examples of cytoplasmic RNP condensates, while the nucleolus and Cajal bodies are representative nuclear RNP condensates. In neurons, RNP condensates promote long-range mRNA transport and local translation in the dendrites and axon, and are essential for spatiotemporal regulation of gene expression, axonal integrity and synaptic function. Mutations of RBPs and/or pathologic mislocalization and aggregation of RBPs are hallmarks of several neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and Alzheimer's disease. ALS/FTD-linked mutations of RBPs alter the strength and reversibility of multivalent interactions with other RBPs and RNAs, resulting in aberrant phase transitions. These aberrant RNP condensates have detrimental functional consequences on mRNA stability, localization, and translation, and ultimately lead to compromised axonal integrity and synaptic function in disease. Pathogenic protein aggregation is dependent on various factors, and aberrant dynamically arrested RNP condensates may serve as an initial nucleation step for pathologic aggregate formation. Recent studies have focused on identifying mechanisms by which neurons resolve phase transitioned condensates to prevent the formation of pathogenic inclusions/aggregates. The present review focuses on the phase separation of neurodegenerative disease-linked RBPs, physiological functions of RNP condensates, and the pathologic role of aberrant phase transitions in neurodegenerative disease, particularly ALS/FTD. We also examine cellular mechanisms that contribute to the resolution of aberrant condensates in neurons, and potential therapeutic approaches to resolve aberrantly phase transitioned condensates at a molecular level.}, } @article {pmid37720544, year = {2023}, author = {McGoldrick, P and Robertson, J}, title = {Unraveling the impact of disrupted nucleocytoplasmic transport systems in C9orf72-associated ALS.}, journal = {Frontiers in cellular neuroscience}, volume = {17}, number = {}, pages = {1247297}, pmid = {37720544}, issn = {1662-5102}, abstract = {Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are two adult-onset neurodegenerative diseases that are part of a common disease spectrum due to clinical, genetic, and pathological overlap. A prominent genetic factor contributing to both diseases is a hexanucleotide repeat expansion in a non-coding region of the C9orf72 gene. This mutation in C9orf72 leads to nuclear depletion and cytoplasmic aggregation of Tar DNA-RNA binding protein 43 (TDP-43). TDP-43 pathology is characteristic of the majority of ALS cases, irrespective of disease causation, and is present in ~50% of FTD cases. Defects in nucleocytoplasmic transport involving the nuclear pore complex, the Ran-GTPase cycle, and nuclear transport factors have been linked with the mislocalization of TDP-43. Here, we will explore and discuss the implications of these system abnormalities of nucleocytoplasmic transport in C9orf72-ALS/FTD, as well as in other forms of familial and sporadic ALS.}, } @article {pmid37720012, year = {2023}, author = {Simmatis, L and Robin, J and Spilka, M and Yunusova, Y}, title = {Detecting bulbar amyotrophic lateral sclerosis (ALS) using automatic acoustic analysis.}, journal = {Research square}, volume = {}, number = {}, pages = {}, pmid = {37720012}, issn = {2693-5015}, support = {R01 DC013547/DC/NIDCD NIH HHS/United States ; }, abstract = {Home-based speech assessments have the potential to dramatically improve ALS clinical practice and facilitate patient stratification for ALS clinical trials. Acoustic speech analysis has demonstrated the ability to capture a variety of relevant speech motor impairments, but implementation has been hindered by both the nature of lab-based assessments (requiring travel and time for patients) and also by the opacity of some acoustic feature analysis methods. Furthermore, these challenges and others have obscured the ability to distinguish different ALS disease stages/severities. Validation of remote-capable acoustic analysis tools could enable detection of early signs of ALS, and these tools could be deployed to screen and monitor patients without requiring clinic visits. Here, we sought to determine whether acoustic features gathered using a remote-capable assessment app could detect ALS as well as different levels of speech impairment severity resulting from ALS. Speech samples (readings of a standardized, 99-word passage) from 119 ALS patients with varying degrees of disease severity as well as 22 neurologically healthy participants were analyzed, and 53 acoustic features were extracted. Patients were stratified into early and late stages of disease (ALS-early/ALS-E and ALS-late/ALS-L) based on the ALS Functional Ratings Scale - Revised bulbar score (FRS-bulb). Data were analyzed using a sparse Bayesian logistic regression classifier. It was determined that the current relatively small set of acoustic features could distinguish between ALS and controls well (area under receiver operating characteristic curve/AUROC = 0.85), that the ALS-E patients could be separated well from control participants (AUROC = 0.78), and that ALS-E and ALS-L patients could be reasonably separated (AUROC = 0.70). These results highlight the potential for remote acoustic analyses to detect and stratify ALS.}, } @article {pmid37717009, year = {2023}, author = {Malnar Črnigoj, M and Čerček, U and Yin, X and Ho, MT and Repic Lampret, B and Neumann, M and Hermann, A and Rouleau, G and Suter, B and Mayr, M and Rogelj, B}, title = {Phenylalanine-tRNA aminoacylation is compromised by ALS/FTD-associated C9orf72 C4G2 repeat RNA.}, journal = {Nature communications}, volume = {14}, number = {1}, pages = {5764}, pmid = {37717009}, issn = {2041-1723}, mesh = {Humans ; Transfer RNA Aminoacylation ; Aminoacylation ; *Amyotrophic Lateral Sclerosis/genetics ; *Frontotemporal Dementia/genetics ; C9orf72 Protein/genetics ; Phenylalanine/genetics ; RNA, Transfer, Phe ; RNA, Antisense ; }, abstract = {The expanded hexanucleotide GGGGCC repeat mutation in the C9orf72 gene is the main genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia. Under one disease mechanism, sense and antisense transcripts of the repeat are predicted to bind various RNA-binding proteins, compromise their function and cause cytotoxicity. Here we identify phenylalanine-tRNA synthetase (FARS) subunit alpha (FARSA) as the main interactor of the CCCCGG antisense repeat RNA in cytosol. The aminoacylation of tRNA[Phe] by FARS is inhibited by antisense RNA, leading to decreased levels of charged tRNA[Phe]. Remarkably, this is associated with global reduction of phenylalanine incorporation in the proteome and decrease in expression of phenylalanine-rich proteins in cellular models and patient tissues. In conclusion, this study reveals functional inhibition of FARSA in the presence of antisense RNA repeats. Compromised aminoacylation of tRNA could lead to impairments in protein synthesis and further contribute to C9orf72 mutation-associated pathology.}, } @article {pmid37714849, year = {2023}, author = {Li, J and Jaiswal, MK and Chien, JF and Kozlenkov, A and Jung, J and Zhou, P and Gardashli, M and Pregent, LJ and Engelberg-Cook, E and Dickson, DW and Belzil, VV and Mukamel, EA and Dracheva, S}, title = {Divergent single cell transcriptome and epigenome alterations in ALS and FTD patients with C9orf72 mutation.}, journal = {Nature communications}, volume = {14}, number = {1}, pages = {5714}, pmid = {37714849}, issn = {2041-1723}, support = {R01 MH122590/MH/NIMH NIH HHS/United States ; I01 BX005585/BX/BLRD VA/United States ; R01 MH122592/MH/NIMH NIH HHS/United States ; I01 BX003625/BX/BLRD VA/United States ; U01 MH122590/MH/NIMH NIH HHS/United States ; P01 AG003949/AG/NIA NIH HHS/United States ; U01 MH122592/MH/NIMH NIH HHS/United States ; R01 AG067151/AG/NIA NIH HHS/United States ; }, mesh = {Humans ; *Frontotemporal Dementia/genetics ; *Amyotrophic Lateral Sclerosis/genetics ; C9orf72 Protein/genetics ; Transcriptome/genetics ; Epigenome ; Mutation ; }, abstract = {A repeat expansion in the C9orf72 (C9) gene is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Here we investigate single nucleus transcriptomics (snRNA-seq) and epigenomics (snATAC-seq) in postmortem motor and frontal cortices from C9-ALS, C9-FTD, and control donors. C9-ALS donors present pervasive alterations of gene expression with concordant changes in chromatin accessibility and histone modifications. The greatest alterations occur in upper and deep layer excitatory neurons, as well as in astrocytes. In neurons, the changes imply an increase in proteostasis, metabolism, and protein expression pathways, alongside a decrease in neuronal function. In astrocytes, the alterations suggest activation and structural remodeling. Conversely, C9-FTD donors have fewer high-quality neuronal nuclei in the frontal cortex and numerous gene expression changes in glial cells. These findings highlight a context-dependent molecular disruption in C9-ALS and C9-FTD, indicating unique effects across cell types, brain regions, and diseases.}, } @article {pmid37714236, year = {2023}, author = {Santhanam, V and Modi, P and Mishra, UK and Jahan, I and Ramesh, NG and Deep, S}, title = {Rational design and synthesis of novel triazole- and tetrazole-fused iminosugars as potential inhibitors of amyotrophic lateral sclerosis (ALS) linked SOD1 aggregation.}, journal = {International journal of biological macromolecules}, volume = {253}, number = {Pt 4}, pages = {126900}, doi = {10.1016/j.ijbiomac.2023.126900}, pmid = {37714236}, issn = {1879-0003}, mesh = {Humans ; Superoxide Dismutase-1/genetics ; *Amyotrophic Lateral Sclerosis ; Superoxide Dismutase/genetics ; Mutation ; }, abstract = {In this manuscript we report the first example of an iminosugar that inhibits superoxide dismutase fibrillation associated with the amyotrophic lateral sclerosis (ALS). The present work involves synthesis of novel triazole and tetrazole embedded iminosugars, synthesized in 11-13 high yielding steps starting from readily available tri-O-benzyl-D-glucal and proceeding through a concomitant azidation - thermal intramolecular [3 + 2] cycloaddition reaction as the key step. One of these pre-designed iminosugars was found to inhibit fibrillation of SOD1 and also has shown propensity to break pre-formed fibrils. Docking and MD simulation studies suggest that the most probable interaction of this compound is a hydrogen bonding with Arg69, a loop IV residue of SOD1, which has a crucial role in stabilizing the native conformation of SOD1.}, } @article {pmid37713127, year = {2024}, author = {Aust, E and Graupner, ST and Günther, R and Linse, K and Joos, M and Grosskreutz, J and Prudlo, J and Pannasch, S and Hermann, A}, title = {Impairment of oculomotor functions in patients with early to advanced amyotrophic lateral sclerosis.}, journal = {Journal of neurology}, volume = {271}, number = {1}, pages = {325-339}, pmid = {37713127}, issn = {1432-1459}, support = {01VSF16026//Gemeinsame Bundesausschuss/ ; 13GW0482//Bundesministerium für Bildung und Forschung/ ; }, mesh = {Humans ; *Saccades ; *Amyotrophic Lateral Sclerosis ; Eye Movements ; Pursuit, Smooth ; }, abstract = {Amyotrophic lateral sclerosis (ALS) can result into an incomplete locked in state (iLIS), in which communication depends on eye tracking computer devices. Oculomotor function impairments in ALS have been reported, but there is little research, particularly with respect to patients in iLIS. In the present study, we compared reflexive and executive oculomotor function by means of an eye tracking test battery between three groups: advanced ALS patients in iLIS (n = 22), patients in early to middle ALS stages (n = 44) and healthy subjects (n = 32). Patients with ALS showed significant deteriorations in oculomotor functions, with stronger impairments in iLIS. More specifically, ALS patients produced visually guided prosaccades with longer latencies and more frequent hypometria compared to healthy subjects. Longest latencies were obtained in iLIS patients, with a stronger prolongation for vertical than for horizontal prosaccades. ALS patients made more antisaccade errors and generated antisaccades with longer latencies. Smooth pursuit was also impaired in ALS. In the earlier ALS stages, bulbar onset patients presented stronger antisaccade and smooth pursuit deficits than spinal onset patients. Our findings reveal a relevant deterioration of important oculomotor functions in ALS, which increases in iLIS. It includes impairments of reflexive eye movements to loss of executive inhibitory control, indicating a progressing pathological involvement of prefrontal, midbrain and brainstem areas. The assessment of oculomotor functions may therefore provide clinically relevant bio- and progression marker, particularly in advanced ALS.}, } @article {pmid37712858, year = {2024}, author = {Al-Kuraishy, HM and Jabir, MS and Al-Gareeb, AI and Saad, HM and Batiha, GE and Klionsky, DJ}, title = {The beneficial role of autophagy in multiple sclerosis: Yes or No?.}, journal = {Autophagy}, volume = {20}, number = {2}, pages = {259-274}, pmid = {37712858}, issn = {1554-8635}, support = {R35 GM131919/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Mice ; *Multiple Sclerosis/metabolism ; Leukocytes, Mononuclear/metabolism ; Autophagy ; Central Nervous System ; *Encephalomyelitis, Autoimmune, Experimental ; Mice, Inbred C57BL ; }, abstract = {Multiple sclerosis (MS) is a chronic progressive demyelinating disease of the central nervous system (CNS) due to an increase of abnormal peripherally auto-reactive T lymphocytes which elicit autoimmunity. The main pathophysiology of MS is myelin sheath damage by immune cells and a defect in the generation of myelin by oligodendrocytes. Macroautophagy/autophagy is a critical degradation process that eliminates dysfunctional or superfluous cellular components. Autophagy has the property of a double-edged sword in MS in that it may have both beneficial and detrimental effects on MS neuropathology. Therefore, this review illustrates the protective and harmful effects of autophagy with regard to this disease. Autophagy prevents the progression of MS by reducing oxidative stress and inflammatory disorders. In contrast, over-activated autophagy is associated with the progression of MS neuropathology and in this case the use of autophagy inhibitors may alleviate the pathogenesis of MS. Furthermore, autophagy provokes the activation of different immune and supporting cells that play an intricate role in the pathogenesis of MS. Autophagy functions in the modulation of MS neuropathology by regulating cell proliferation related to demyelination and remyelination. Autophagy enhances remyelination by increasing the activity of oligodendrocytes, and astrocytes. However, autophagy induces demyelination by activating microglia and T cells. In conclusion, specific autophagic activators of oligodendrocytes, and astrocytes, and specific autophagic inhibitors of dendritic cells (DCs), microglia and T cells induce protective effects against the pathogenesis of MS.Abbreviations: ALS: amyotrophic lateral sclerosis; APCs: antigen-presenting cells; BBB: blood-brain barrier; CSF: cerebrospinal fluid; CNS: central nervous system; DCs: dendritic cells; EAE: experimental autoimmune encephalomyelitis; ER: endoplasmic reticulum; LAP: LC3-associated phagocytosis; MS: multiple sclerosis; NCA: non-canonical autophagy; OCBs: oligoclonal bands; PBMCs: peripheral blood mononuclear cells; PD: Parkinson disease; ROS: reactive oxygen species; UPR: unfolded protein response.}, } @article {pmid37712540, year = {2023}, author = {Zhao, R and Huang, QW and Yu, ZY and Han, Z and Fan, K and Zhao, ZH and Nie, DX}, title = {[Simultaneous determination of 36 mycotoxins in fruits by QuEChERS coupled with ultra performance liquid chromatography-tandem mass spectrometry].}, journal = {Se pu = Chinese journal of chromatography}, volume = {41}, number = {9}, pages = {760-770}, pmid = {37712540}, issn = {1872-2059}, mesh = {Animals ; Humans ; Chromatography, Liquid ; *Fruit ; Tandem Mass Spectrometry ; *Patulin ; Acetonitriles ; }, abstract = {Mycotoxins are secondary metabolites produced by toxigenic fungi under specific environmental conditions. Fruits, owing to their high moisture content, rich nutrition, and improper harvest or storage conditions, are highly susceptible to various mycotoxins, such as ochratoxin A (OTA), zearalenone (ZEN), patulin (PAT), Alternaria toxins, etc. These mycotoxins can cause acute and chronic toxic effects (teratogenicity, mutagenicity, and carcinogenicity, etc) in animals and humans. Given the high toxicity and wide prevalence of mycotoxins, establishing an efficient analytical method to detect multiple mycotoxins simultaneously in different types of fruits is of great importance. Conventional mycotoxin detection methods rely on high performance liquid chromatography (HPLC) coupled with mass spectrometry (MS). However, fruit sample matrices contain large amounts of pigments, cellulose, and minerals, all of which dramatically impede the detection of trace mycotoxins in fruits. Therefore, the efficient enrichment and purification of multiple mycotoxins in fruit samples is crucial before instrumental analysis. In this study, a reliable method based on a QuEChERs sample preparation approach coupled with ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was established to determine 36 mycotoxins in fruits. In the optimal extraction method, 2.0 g of a sample was extracted with 10 mL of acetic acid-acetonitrile-water (1∶79∶20, v/v/v) in a 50 mL centrifuge tube, vortexed for 30 s, and ultrasonicated for 40 min. The mixture was then salted out with 2.0 g of anhydrous MgSO4 and 0.5 g of NaCl and centrifuged for 5 min. Next, 6 mL of the supernatant was purified using 85 mg of octadecylsilane-bonded silica gel (C18) and 15 mg of N-propylethylenediamine (PSA). After vigorous shaking and centrifugation, the supernatant was collected and dried with nitrogen at 40 ℃. Finally, the residues were redissolved in 1 mL of 5 mmol/L ammonium acetate aqueous solution-acetonitrile (50∶50, v/v) and passed through a 0.22 μm nylon filter before analysis. The mycotoxins were separated on a Waters XBridge BEH C18 column using a binary gradient mixture of ammonium acetate aqueous solution and methanol. The injection volume was 3 μL. The mycotoxins were analyzed in multiple reaction monitoring (MRM) mode under both positive and negative electrospray ionization. Quantitative analysis was performed using an external standard method with matrix-matched calibration curves. Under optimal conditions, good linear relationships were obtained in the respective linear ranges, with correlation coefficients (R[2]) no less than 0.990. The limits of detection (LODs) and quantification (LOQs) were 0.02-5 and 0.1-10 μg/kg, respectively. The recoveries of the 36 mycotoxins in fruits ranged from 77.0% to 118.9% at low, medium, and high spiked levels, with intra- and inter-day precisions in the range of 1.3%-14.9% and 0.2%-17.3%, respectively. The validated approach was employed to investigate mycotoxin contamination in actual fruit samples, including strawberry, grape, pear, and peach (15 samples of each type). Eleven mycotoxins, namely, altenuene (ALT), altenusin (ALS), alternariol-methyl ether (AME), tenuazonic acid (TeA), tentoxin (Ten), OTA, beauvericin (BEA), PAT, zearalanone (ZAN), T-2 toxin (T2), and mycophenolic acid (MPA), were found in the samples; three samples were contaminated with multiple mycotoxins. The incidence rates of mycotoxins in strawberry, grape, pear, and peach were 27%, 40%, 40%, and 33%, respectively. In particular, Alternaria toxins were the most frequently found mycotoxins in these fruits, with an incidence of 15%. The proposed method is simple, rapid, accurate, sensitive, reproducible, and stable; thus, it is suitable for the simultaneous detection of the 36 mycotoxins in different fruits.}, } @article {pmid37711512, year = {2023}, author = {Tomiyama, ALMR and Cartarozzi, LP and de Oliveira Coser, L and Chiarotto, GB and Oliveira, ALR}, title = {Neuroprotection by upregulation of the major histocompatibility complex class I (MHC I) in SOD1[G93A] mice.}, journal = {Frontiers in cellular neuroscience}, volume = {17}, number = {}, pages = {1211486}, pmid = {37711512}, issn = {1662-5102}, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that progressively affects motoneurons, causing muscle atrophy and evolving to death. Astrocytes inhibit the expression of MHC-I by neurons, contributing to a degenerative outcome. The present study verified the influence of interferon β (IFN β) treatment, a proinflammatory cytokine that upregulates MHC-I expression, in SOD1[G93A] transgenic mice. For that, 17 days old presymptomatic female mice were subjected to subcutaneous application of IFN β (250, 1,000, and 10,000 IU) every other day for 20 days. Rotarod motor test, clinical score, and body weight assessment were conducted every third day throughout the treatment period. No significant intergroup variations were observed in such parameters during the pre-symptomatic phase. All mice were then euthanized, and the spinal cords collected for comparative analysis of motoneuron survival, reactive gliosis, synapse coverage, microglia morphology classification, cytokine analysis by flow cytometry, and RT-qPCR quantification of gene transcripts. Additionally, mice underwent Rotarod motor assessment, weight monitoring, and neurological scoring. The results show that IFN β treatment led to an increase in the expression of MHC-I, which, even at the lowest dose (250 IU), resulted in a significant increase in neuronal survival in the ALS presymptomatic period which lasted until the onset of the disease. The treatment also influenced synaptic preservation by decreasing excitatory inputs and upregulating the expression of AMPA receptors by astrocytes. Microglial reactivity quantified by the integrated density of pixels did not decrease with treatment but showed a less activated morphology, coupled with polarization to an M1 profile. Disease progression upregulated gene transcripts for pro- and anti-inflammatory cytokines, and IFN β treatment significantly decreased mRNA expression for IL4. Overall, the present results demonstrate that a low dosage of IFN β shows therapeutic potential by increasing MHC-I expression, resulting in neuroprotection and immunomodulation.}, } @article {pmid37711501, year = {2023}, author = {Zare, H and Najand, B and Fugal, A and Assari, S}, title = {Allostatic load in the US general population: Race and educational intersection.}, journal = {Public health in practice (Oxford, England)}, volume = {6}, number = {}, pages = {100425}, pmid = {37711501}, issn = {2666-5352}, abstract = {OBJECTIVES: Educational attainment is a protective factor against poor health, but high educational attainment has a weaker effect on black people than on white people; this pattern has been called marginalization-related diminished returns (MDRs). Using a national sample of white people and black people 25 years and above, this study estimates the association between high educational attainment and allostatic load between black people and white people, and within each group.

STUDY DESIGN: This cross-sectional study uses data from the National Health and Nutrition Examination Survey (NHANES) between 1999 and 2016, including 2761 black people and 7058 white people. The outcome variable of interest was the Allostatic Load Scale (AL). We created the allostatic load scale by using 8 biomarkers, then created a binary variable (if ALS≥4 as 1 and ALS<4 as 0) to present elevated AL.

METHODS: We used several weighted modified Poisson regression models controlling for educational attainment (a predictor) and race (a moderator variable), age, sex, and marital status. We also controlled the models for smoking and drinking status as health behavior variables. As a sensitivity analysis, we ran several sets of regression analysis using the AL scale as a continuous outcome variable.

RESULTS: We found an inverse association between AL and educational attainment. The interaction between race and education has resulted in an inverse association between AL and educational attainment, with a weaker association in black people than in white people. We found similar findings by running regression models with AL as a continuous variable.

CONCLUSIONS: We observed a weaker association between educational attainment and AL in black people than in white people, suggesting that educational attainment has more robust protection against allostatic load for white people than black people.}, } @article {pmid37711011, year = {2023}, author = {Rodrigues, RB and Orsini, M and Neves, SV and de Rezende Pinto, WBV and da Silva Catarino, AM and Pereira, DA and Oliveira, ASB}, title = {Differential Diagnosis or Etiology: A Case Report on Amyotrophic Lateral Sclerosis-like Neuropathy Associated with HIV Infection.}, journal = {Current HIV research}, volume = {21}, number = {5}, pages = {323-329}, doi = {10.2174/1570162X21666230914104220}, pmid = {37711011}, issn = {1873-4251}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/complications/drug therapy ; *HIV Infections/complications/drug therapy ; Diagnosis, Differential ; }, abstract = {BACKGROUND: Retroviruses are described as a risk factor for chronic neuropathy. However, it is still unknown if they can work as amyotrophic lateral sclerosis triggers. Over the years, some cases of this association have been described with heterogenous disclosures.

CASE REPRESENTATION: This study aimed to report a case of HIV and ALS-like neuropathy and briefly discuss peculiarities of clinical aspects, such as physiopathology and treatment options. The patient underwent neurological examination associated with blood tests, electromyography, analysis of cerebrospinal fluid, and imaging studies.

DISCUSSION: A non-systematic review was performed in major databases regarding the topic. The case presented mixed upper and lower motor neuron signs and was framed as a probable case of ALS following the present criteria.

CONCLUSION: After a short follow-up and viral load cleansing, neurological stabilization was achieved.}, } @article {pmid37710422, year = {2024}, author = {Thomas, A and Garg, D and Srivastava, AK and Kumar, A and Pandit, AK and Vibha, D and Vivekanandhan, S and Shukla, G and Prasad, K}, title = {Clinical factors and vascular endothelial growth factor as determinants of disease progression in Indian patients with amyotrophic lateral sclerosis.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {25}, number = {1-2}, pages = {46-52}, doi = {10.1080/21678421.2023.2256362}, pmid = {37710422}, issn = {2167-9223}, mesh = {Humans ; Male ; Adult ; Middle Aged ; Female ; *Amyotrophic Lateral Sclerosis/diagnosis ; Vascular Endothelial Growth Factor A ; Cross-Sectional Studies ; Biomarkers ; Disease Progression ; }, abstract = {OBJECTIVE: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder. Prognostication remains sub-optimally defined. We aimed to assess clinical determinants of disease progression rates in Indian patients with ALS and to assess the role of vascular endothelial growth factor (VEGF) in disease progression.

METHODS: In this cross-sectional study, consecutive patients with clinically definite/probable ALS according to the revised El Escorial criteria and controls were included. Patients were classified into fast or slow progressors based on disease progression rate (DPR). Serum and CSF VEGF level was assessed for patients and controls.

RESULTS: Of 142 patients recruited, 93 (65.5%) were male. Mean age at enrollment was 49.37 ± 12.65 years. Mean duration of symptoms was 20.53 ± 20.88 months. Mean DPR was 1.14 ± 0.94. Based on DPR, 81 (57%) patients were slow progressors and 61 (43%) were fast progressors. Univariate analysis demonstrated a statistically significant association of DPR with age at onset, symptom duration, time to spread, wasting of small muscles of the hand, frontal release signs, and neurophysiologic bulbar abnormalities. On multivariate analysis, age at onset and symptom duration had a significant association with disease progression. The CSF VEGF levels of ALS patients (46.18 ± 27.8) were significantly elevated compared to controls (25.95 ± 25.64 pg/ml) (p = 0.001), but not serum VEGF.

CONCLUSION: Age at symptom onset and duration of disease had a significant impact on disease progression in Indian patients with ALS. CSF VEGF levels were significantly elevated in ALS compared to controls, indicating the role of CSF VEGF as a potential biomarker.}, } @article {pmid37710261, year = {2023}, author = {Zeng, Q and Wang, K and Liu, WX and Zeng, JZ and Li, XL and Zhang, QF and Ren, SQ and Xu, WM}, title = {Efficacy of high-fidelity simulation in advanced life support training: a systematic review and meta-analysis of randomized controlled trials.}, journal = {BMC medical education}, volume = {23}, number = {1}, pages = {664}, pmid = {37710261}, issn = {1472-6920}, support = {2023NSFSC1475//Sichuan Province Science and Technology Support Program/ ; 2023-207//Health Commission of Sichuan Province/ ; 2021ZX01//Sichuan Provincial People's Hospital/ ; KLET-202104//Ministry of Education Hainan Medical University/ ; R2021012//Peking Union Medical Foundation/ ; }, mesh = {Humans ; Computer Simulation ; Educational Status ; *High Fidelity Simulation Training ; Randomized Controlled Trials as Topic ; }, abstract = {BACKGROUND: Simulation is an increasingly used novel method for the education of medical professionals. This study aimed to systematically review the efficacy of high-fidelity (HF) simulation compared with low-fidelity (LF) simulation or no simulation in advanced life support (ALS) training.

METHODS: A comprehensive search of the PubMed, Chinese Biomedicine Database, Embase, CENTRAL, ISI, and China Knowledge Resource Integrated Database was performed to identify randomized controlled trials (RCTs) that evaluated the use of HF simulation in ALS training. Quality assessment was based on the Cochrane Handbook for Systematic Reviews of Interventions version 5.0.1. The primary outcome was the improvement of knowledge and skill performance. The secondary outcomes included the participants' confidence and satisfaction at the course conclusion, skill performance at one year, skill performance in actual resuscitation, and patient outcomes. Data were synthesized using the RevMan 5.4 software.

RESULTS: Altogether, 25 RCTs with a total of 1,987 trainees were included in the meta-analysis. In the intervention group, 998 participants used HF manikins, whereas 989 participants received LF simulation-based or traditional training (classical training without simulation). Pooled data from the RCTs demonstrated a benefit in improvement of knowledge [standardized mean difference (SMD) = 0.38; 95% confidence interval (CI): 0.18-0.59, P = 0.0003, I[2] = 70%] and skill performance (SMD = 0.63; 95% CI: 0.21-1.04, P = 0.003, I[2] = 92%) for HF simulation when compared with LF simulation and traditional training. The subgroup analysis revealed a greater benefit in knowledge with HF simulation compared with traditional training at the course conclusion (SMD = 0.51; 95% CI: 0.20-0.83, P = 0.003, I[2] = 61%). Studies measuring knowledge at three months, skill performance at one year, teamwork behaviors, participants' satisfaction and confidence demonstrated no significant benefit for HF simulation.

CONCLUSIONS: Learners using HF simulation more significantly benefited from the ALS training in terms of knowledge and skill performance at the course conclusion. However, further research is necessary to enhance long-term retention of knowledge and skill in actual resuscitation and patient's outcomes.}, } @article {pmid37709948, year = {2023}, author = {Goutman, SA and Savelieff, MG and Jang, DG and Hur, J and Feldman, EL}, title = {The amyotrophic lateral sclerosis exposome: recent advances and future directions.}, journal = {Nature reviews. Neurology}, volume = {19}, number = {10}, pages = {617-634}, pmid = {37709948}, issn = {1759-4766}, support = {R01 TS000327/TS/ATSDR CDC HHS/United States ; K23 ES027221/ES/NIEHS NIH HHS/United States ; R01 ES030049/ES/NIEHS NIH HHS/United States ; R01 NS120926/NS/NINDS NIH HHS/United States ; R01 NS127188/NS/NINDS NIH HHS/United States ; R01 TS000289/TS/ATSDR CDC HHS/United States ; R01TS000289/ACL/ACL HHS/United States ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/etiology/genetics ; *Exposome ; Environmental Exposure/adverse effects ; Mutation ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal disease of motor neuron degeneration with typical survival of only 2-5 years from diagnosis. The causes of ALS are multifactorial: known genetic mutations account for only around 70% of cases of familial ALS and 15% of sporadic cases, and heritability estimates range from 8% to 61%, indicating additional causes beyond genetics. Consequently, interest has grown in environmental contributions to ALS risk and progression. The gene-time-environment hypothesis posits that ALS onset occurs through an interaction of genes with environmental exposures during ageing. An alternative hypothesis, the multistep model of ALS, suggests that several hits, at least some of which could be environmental, are required to trigger disease onset, even in the presence of highly penetrant ALS-associated mutations. Studies have sought to characterize the ALS exposome - the lifetime accumulation of environmental exposures that increase disease risk and affect progression. Identifying the full scope of environmental toxicants that enhance ALS risk raises the prospect of preventing disease by eliminating or mitigating exposures. In this Review, we summarize the evidence for an ALS exposome, discussing the strengths and limitations of epidemiological studies that have identified contributions from various sources. We also consider potential mechanisms of exposure-mediated toxicity and suggest future directions for ALS exposome research.}, } @article {pmid37709589, year = {2023}, author = {Jin, J and Zhong, XB}, title = {ASO drug Qalsody (tofersen) targets amyotrophic lateral sclerosis.}, journal = {Trends in pharmacological sciences}, volume = {44}, number = {12}, pages = {1043-1044}, pmid = {37709589}, issn = {1873-3735}, support = {R35 GM140862/GM/NIGMS NIH HHS/United States ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy ; Oligonucleotides ; }, } @article {pmid37709437, year = {2023}, author = {Cavallini, N and Strani, L and Becchi, PP and Pizzamiglio, V and Michelini, S and Savorani, F and Cocchi, M and Durante, C}, title = {Tracing the identity of Parmigiano Reggiano "Prodotto di Montagna - Progetto Territorio" cheese using NMR spectroscopy and multivariate data analysis.}, journal = {Analytica chimica acta}, volume = {1278}, number = {}, pages = {341761}, doi = {10.1016/j.aca.2023.341761}, pmid = {37709437}, issn = {1873-4324}, mesh = {*Cheese ; Data Analysis ; Gene Library ; Metabolomics ; Multivariate Analysis ; }, abstract = {BACKGROUND: Nuclear magnetic resonance (NMR) spectroscopy is one of the well-established tools for food metabolomic analysis, as it proved to be very effective in authenticity and quality control of dairy products, as well as to follow product evolution during processing and storage. The analytical assessment of the EU mountain denomination label, specifically for Parmigiano Reggiano "Prodotto di Montagna - Progetto Territorio" (Mountain-CQ) cheese, has received limited attention. Although it was established in 2012 the EU mountain denomination label has not been much studied from an analytical point of view. Nonetheless, tracing a specific profile for the mountain products is essential to support the value chain of this specialty.

RESULTS: The aim of the study was to produce an identity profile for Parmigiano Reggiano "Prodotto di Montagna - Progetto Territorio" (Mountain-CQ) cheese, and to differentiate it from Parmigiano Reggiano PDO samples (conventional-PDO) using [1]H NMR spectroscopy coupled with multivariate data analysis. Three different approaches were applied and compared. First, the spectra-as-such were analysed after proper preprocessing. For the other two approaches, Multivariate Curve Resolution-Alternating Least Squares (MCR-ALS) was used for signals resolution and features extraction, either individually on manually-defined spectral intervals or by reapplying MCR-ALS on the whole spectra with selectivity constraints using the reconstructed "pure profiles" as initial estimates and targets. All approaches provided comparable information regarding the samples' distribution, as in all three cases the separation between the two product categories conventional-PDO and Mountain-CQ could be highlighted. Moreover, a novel MATLAB toolbox for features extraction via MCR-ALS was developed and used in synergy with the Chenomx library, allowing for a putative identification of the selected features.

SIGNIFICANCE: A first identity profile for Parmigiano Reggiano "Prodotto di Montagna - Progetto Territorio" obtained by interpreting the metabolites signals in NMR spectroscopy was obtained. Our workflow and toolbox for generating the features dataset allows a more straightforward interpretation of the results, to overcome the limitations due to dimensionality and to peaks overlapping, but also to include the signals assignment and matching since the early stages of the data processing and analysis.}, } @article {pmid37708975, year = {2024}, author = {Isaq, NA and Link, JL}, title = {Response to Papp et al's "Long-term safety and disease control with ruxolitinib cream in atopic dermatitis: Results from two phase 3 studies".}, journal = {Journal of the American Academy of Dermatology}, volume = {90}, number = {1}, pages = {e19-e20}, doi = {10.1016/j.jaad.2023.04.076}, pmid = {37708975}, issn = {1097-6787}, mesh = {Humans ; *Dermatitis, Atopic/drug therapy ; Nitriles ; Pyrimidines/adverse effects ; Pyrazoles/adverse effects ; }, } @article {pmid37707250, year = {2023}, author = {Guo, Y and Jin, W and Wang, W and He, Y and Qiu, S}, title = {Baseline correction for Raman spectra using a spectral estimation-based asymmetrically reweighted penalized least squares method.}, journal = {Applied optics}, volume = {62}, number = {18}, pages = {4766-4776}, doi = {10.1364/AO.489478}, pmid = {37707250}, issn = {1539-4522}, abstract = {Baseline correction is necessary for the qualitative and quantitative analysis of samples because of the existence of background fluorescence interference in Raman spectra. The asymmetric least squares (ALS) method is an adaptive and automated algorithm that avoids peak detection operations along with other user interactions. However, current ALS-based improved algorithms only consider the smoothness configuration of regions where the signals are greater than the fitted baseline, which results in smoothing distortion. In this paper, an asymmetrically reweighted penalized least squares method based on spectral estimation (SEALS) is proposed. SEALS considers not only the uniform distribution of additive noise along the baseline but also the energy distribution of the signal above and below the fitted baseline. The energy distribution is estimated using inverse Fourier and autoregressive models to create a spectral estimation kernel. This kernel effectively optimizes and balances the asymmetric weight assigned to each data point. By doing so, it resolves the issue of local oversmoothing that is typically encountered in the asymmetrically reweighted penalized least squares method. This oversmoothing problem can negatively impact the iteration depth and accuracy of baseline fitting. In comparative experiments on simulated spectra, SEALS demonstrated a better baseline fitting performance compared to several other advanced baseline correction methods, both under moderate and strong fluorescence backgrounds. It has also been proven to be highly resistant to noise interference. When applied to real Raman spectra, the algorithm correctly restored the weak peaks and removed the fluorescence peaks, demonstrating the effectiveness of this method. The computation time of the proposed method was approximately 0.05 s, which satisfies the real-time baseline correction requirements of practical spectroscopy acquisition.}, } @article {pmid37706096, year = {2023}, author = {Stipa, G and Ancidoni, A and Vanacore, N and Bellomo, G}, title = {Raw Water and ALS: A Unifying Hypothesis for the Environmental Agents Involved in ALS.}, journal = {Annals of neurosciences}, volume = {30}, number = {2}, pages = {124-132}, pmid = {37706096}, issn = {0972-7531}, abstract = {Different studies identified the presence of several altered genes in familial and sporadic amyotrophic lateral sclerosis (ALS) forms. The experimental data, together with the epidemiological data, would seem to suggest the existence of molecular mechanisms (e.g., axonal transport) related to these genes, together with a susceptibility of the same genes to certain environmental factors that would therefore suggest an impact of the environment on the etiopathogenesis of ALS. In our review, we considered the most relevant environmental clusters around the world, collecting different hypotheses and underlining common environmental factors among the different clusters. Moreover, further epidemiological data identified a higher risk of ALS in professional athletes and, in particular, in soccer and football players. Despite this increased risk of ALS highlighted by the epidemiological evidence in aforementioned sports, the mechanisms remain unclear. At last, the use of raw water has been associated with ALS risk. The aim of the present review is to characterize a possible relationship between these clusters, to be explored in the context of the interaction between genetic and environmental factors on the etiopathogenesis of ALS.}, } @article {pmid37705092, year = {2023}, author = {Gerovska, D and Noer, JB and Qin, Y and Ain, Q and Januzi, D and Schwab, M and Witte, OW and Araúzo-Bravo, MJ and Kretz, A}, title = {A distinct circular DNA profile intersects with proteome changes in the genotoxic stress-related hSOD1[G93A] model of ALS.}, journal = {Cell & bioscience}, volume = {13}, number = {1}, pages = {170}, pmid = {37705092}, issn = {2045-3701}, support = {EKFS//Else Kröner-Fresenius-Stiftung/ ; WI 830/12-1//Deutsche Forschungsgemeinschaft/ ; RegenerAging-52-5581-413-FSU-I-03/14//TMWWDG/ ; FF01//Center for Clinical and Translational Research/ ; 899417//HORIZON EUROPE European Innovation Council/ ; PID2020-119715GB-I00/AEI/10.13039/501100011033//Ministerio de Ciencia e Innovación/ ; iDATA-MP//Instituto de Salud Carlos III/ ; iDATA-MP//Instituto de Salud Carlos III/ ; 8088-00049B//Innovationsfonden/ ; CF21-0167//Carlsbergfondet/ ; NNF21OC0072023//Novo Nordisk Fonden/ ; }, abstract = {BACKGROUND: Numerous genes, including SOD1, mutated in familial and sporadic amyotrophic lateral sclerosis (f/sALS) share a role in DNA damage and repair, emphasizing genome disintegration in ALS. One possible outcome of chromosomal instability and repair processes is extrachromosomal circular DNA (eccDNA) formation. Therefore, eccDNA might accumulate in f/sALS with yet unknown function.

METHODS: We combined rolling circle amplification with linear DNA digestion to purify eccDNA from the cervical spinal cord of 9 co-isogenic symptomatic hSOD1[G93A] mutants and 10 controls, followed by deep short-read sequencing. We mapped the eccDNAs and performed differential analysis based on the split read signal of the eccDNAs, referred as DifCir, between the ALS and control specimens, to find differentially produced per gene circles (DPpGC) in the two groups. Compared were eccDNA abundances, length distributions and genic profiles. We further assessed proteome alterations in ALS by mass spectrometry, and matched the DPpGCs with differentially expressed proteins (DEPs) in ALS. Additionally, we aligned the ALS-specific DPpGCs to ALS risk gene databases.

RESULTS: We found a six-fold enrichment in the number of unique eccDNAs in the genotoxic ALS-model relative to controls. We uncovered a distinct genic circulome profile characterized by 225 up-DPpGCs, i.e., genes that produced more eccDNAs from distinct gene sequences in ALS than under control conditions. The inter-sample recurrence rate was at least 89% for the top 6 up-DPpGCs. ALS proteome analyses revealed 42 corresponding DEPs, of which 19 underlying genes were itemized for an ALS risk in GWAS databases. The up-DPpGCs and their DEP tandems mainly impart neuron-specific functions, and gene set enrichment analyses indicated an overrepresentation of the adenylate cyclase modulating G protein pathway.

CONCLUSIONS: We prove, for the first time, a significant enrichment of eccDNA in the ALS-affected spinal cord. Our triple circulome, proteome and genome approach provide indication for a potential importance of certain eccDNAs in ALS neurodegeneration and a yet unconsidered role as ALS biomarkers. The related functional pathways might open up new targets for therapeutic intervention.}, } @article {pmid37704403, year = {2023}, author = {Lin, CC and Hill, CE and Kerber, KA and Burke, JF and Skolarus, LE and Esper, GJ and de Havenon, A and De Lott, LB and Callaghan, BC}, title = {Patient Travel Distance to Neurologist Visits.}, journal = {Neurology}, volume = {101}, number = {18}, pages = {e1807-e1820}, pmid = {37704403}, issn = {1526-632X}, support = {K23 NS126495/NS/NINDS NIH HHS/United States ; UL1 TR001863/TR/NCATS NIH HHS/United States ; }, mesh = {Humans ; United States/epidemiology ; Aged ; *Neurologists ; Medicare ; Cross-Sectional Studies ; *Amyotrophic Lateral Sclerosis ; Travel ; Health Services Accessibility ; }, abstract = {BACKGROUND AND OBJECTIVES: The density of neurologists within a given geographic region varies greatly across the United States. We aimed to measure patient travel distance and travel time to neurologist visits, across neurologic conditions and subspecialties. Our secondary goal was to identify factors associated with long-distance travel for neurologic care.

METHODS: We performed a cross-sectional analysis using a 2018 Medicare sample of patients with at least 1 outpatient neurologist visit. Long-distance travel was defined as driving distance ≥50 miles 1-way to the visit. Travel time was measured as driving time in minutes. Multilevel generalized linear mixed models with logistic link function, which accounted for clustering of patients within hospital referral region and allowed modeling of region-specific random effects, were used to determine the association of patient and regional characteristics with long-distance travel.

RESULTS: We identified 563,216 Medicare beneficiaries with a neurologist visit in 2018. Of them, 96,213 (17%) traveled long distance for care. The median driving distance and time were 81.3 (interquartile range [IQR]: 59.9-144.2) miles and 90 (IQR: 69-149) minutes for patients with long-distance travel compared with 13.2 (IQR: 6.5-23) miles and 22 (IQR: 14-33) minutes for patients without long-distance travel. Comparing across neurologic conditions, long-distance travel was most common for nervous system cancer care (39.6%), amyotrophic lateral sclerosis [ALS] (32.1%), and MS (22.8%). Many factors were associated with long-distance travel, most notably low neurologist density (first quintile: OR 3.04 [95% CI 2.41-3.83] vs fifth quintile), rural setting (4.89 [4.79-4.99]), long-distance travel to primary care physician visit (3.6 [3.51-3.69]), and visits for ALS and nervous system cancer care (3.41 [3.14-3.69] and 5.27 [4.72-5.89], respectively). Nearly one-third of patients bypassed the nearest neurologist by 20+ miles, and 7.3% of patients crossed state lines for neurologist care.

DISCUSSION: We found that nearly 1 in 5 Medicare beneficiaries who saw a neurologist traveled ≥50 miles 1-way for care, and travel burden was most common for lower-prevalence neurologic conditions that required coordinated multidisciplinary care. Important potentially addressable predictors of long-distance travel were low neurologist density and rural location, suggesting interventions to improve access to care such as telemedicine or neurologic subspecialist support to local neurologists. Future work should evaluate differences in clinical outcomes between patients with long-distance travel and those without.}, } @article {pmid37704056, year = {2023}, author = {Tang, J and Kang, Y and Zhou, Y and Chen, Q and Lan, J and Liu, X and Peng, Y}, title = {Umbilical cord mesenchymal stem cell-conditioned medium inhibits microglial activation to ameliorate neuroinflammation in amyotrophic lateral sclerosis mice and cell models.}, journal = {Brain research bulletin}, volume = {202}, number = {}, pages = {110760}, doi = {10.1016/j.brainresbull.2023.110760}, pmid = {37704056}, issn = {1873-2747}, mesh = {Mice ; Animals ; Microglia ; Neuroinflammatory Diseases ; *Amyotrophic Lateral Sclerosis ; Culture Media, Conditioned/pharmacology ; *Neurodegenerative Diseases ; Superoxide Dismutase-1 ; *Mesenchymal Stem Cells ; Mice, Transgenic ; Cytokines ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease for which few effective therapeutic strategies are available. Increasing evidence indicates that neuroinflammation plays a significant role in ALS pathogenesis. Mesenchymal stem cell (MSC)-based therapy has been proposed for the treatment of neurodegenerative diseases, including ALS. In this study, we first demonstrated that systemic administration of conditioned medium derived from umbilical cord MSCs (UCMSC-CM) extends the lifespan of transgenic SOD1-G93A mice, a well-characterized model of familial ALS. Moreover, UCMSC-CM inhibits microglial activation and astrogliosis and alleviates the inflammatory milieu by reducing the release of proinflammatory cytokines and the expression of iNOS in the spinal cord. Using BV-2 cells overexpressing the SOD1-G93A mutant as an ALS cellular model, we uncovered that UCMSC-CM also suppresses the lipopolysaccharide (LPS)-induced inflammatory response, including reduced expression of proinflammatory cytokines and iNOS. Importantly, by culturing astrocytes alone in microglia-conditioned medium (MCM) or together with microglia in a transwell coculture system, we found that UCMSC-CM modulates the secretome of microglia exposed to inflammatory stimuli, thereby preventing the conversion of astrocytes to the A1 neurotoxic phenotype. This study revealed the anti-inflammatory properties of UCMSC-CM and its regulatory effect on glial activation in the treatment of neuroinflammation in ALS, providing strong evidence for the clinical application of UCMSC-CM.}, } @article {pmid37703175, year = {2023}, author = {Runfola, V and Giambruno, R and Caronni, C and Pannese, M and Andolfo, A and Gabellini, D}, title = {MATR3 is an endogenous inhibitor of DUX4 in FSHD muscular dystrophy.}, journal = {Cell reports}, volume = {42}, number = {9}, pages = {113120}, pmid = {37703175}, issn = {2211-1247}, support = {R21 CA249378/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; Amyotrophic Lateral Sclerosis/genetics ; Gene Expression Regulation ; Genes, Homeobox ; *Homeodomain Proteins/genetics/metabolism ; Muscle, Skeletal/metabolism ; *Muscular Dystrophy, Facioscapulohumeral/genetics/metabolism ; Neurodegenerative Diseases/genetics ; Nuclear Matrix-Associated Proteins/metabolism ; RNA-Binding Proteins/metabolism ; }, abstract = {Facioscapulohumeral muscular dystrophy (FSHD) is one of the most common neuromuscular disorders and has no cure. Due to an unknown molecular mechanism, FSHD displays overlapping manifestations with the neurodegenerative disease amyotrophic lateral sclerosis (ALS). FSHD is caused by aberrant gain of expression of the transcription factor double homeobox 4 (DUX4), which triggers a pro-apoptotic transcriptional program resulting in inhibition of myogenic differentiation and muscle wasting. Regulation of DUX4 activity is poorly known. We identify Matrin 3 (MATR3), whose mutation causes ALS and dominant distal myopathy, as a cellular factor controlling DUX4 expression and activity. MATR3 binds to the DUX4 DNA-binding domain and blocks DUX4-mediated gene expression, rescuing cell viability and myogenic differentiation of FSHD muscle cells, without affecting healthy muscle cells. Finally, we characterize a shorter MATR3 fragment that is necessary and sufficient to directly block DUX4-induced toxicity to the same extent as the full-length protein. Collectively, our data suggest MATR3 as a candidate for developing a treatment for FSHD.}, } @article {pmid37700955, year = {2023}, author = {Cardenas, J and Cardenas, JM and Garber, M and Irazuzta, J}, title = {Incidence of Air Leak Syndrome in Pediatric Patients With SARS-COV-2 Pneumonia and Respiratory Failure: A Single-Center Retrospective Study.}, journal = {Cureus}, volume = {15}, number = {8}, pages = {e43329}, pmid = {37700955}, issn = {2168-8184}, abstract = {Air leak syndrome (ALS) is defined as the extrusion of air from an aerated compartment into an unaerated compartment with associated symptoms of respiratory distress. This syndrome can occur as a consequence of trauma, iatrogenic causes, or spontaneously. Retrospective investigations conducted in the adult population have demonstrated an elevated risk of spontaneous ALS development in patients with coronavirus disease 2019 (COVID-19) pneumonia, along with its correlation with mortality. However, no studies have yet explored this phenomenon within the pediatric population. In light of this knowledge gap, we conducted a retrospective chart review comprising 128 pediatric patients ranging in age from one month to 18 years. The primary objective was to assess the incidence of ALS in two distinct groups: patients diagnosed with COVID-19 pneumonia and those with non-COVID-19 viral pneumonia. The groups were compared using Fisher's exact test for sex, the presence of ALS, the requirement of extracorporeal membrane oxygenation (ECMO), and death. The modified Wald method was used to calculate the 95% confidence interval for the mortality rate in patients with COVID-19 pneumonia in the presence of ALS. Our findings revealed a higher prevalence of ALS in patients with COVID-19 pneumonia compared to the non-COVID-19 viral pneumonia group, with a statistically significant P-value of 0.02 and an odds ratio (OR) of 6.72. In terms of mortality rates, there was a statistically significant difference between the two groups (P = 0.025, OR = 1.083). In addition, in patients with ALS in the presence of COVID-19 pneumonia, the mortality rate was 37.5%. However, the requirement of ECMO was not statistically significant (P = 0.16, OR = 1.04). These results suggest that patients with COVID-19 pneumonia have an increased mortality rate and a heightened risk of developing ALS compared to individuals with other viral pneumonias. Furthermore, the presence of ALS was associated with a high mortality rate in COVID-19 pneumonia patients. However, it is crucial to note that obtaining a larger patient sample and involving multiple institutions would be necessary to obtain more consistent and robust data.}, } @article {pmid37700418, year = {2023}, author = {Madanchi, M and Brenner, M and Navarini, AA and Juratli, HA}, title = {[Ageusie als Symptom bei Affenpockeninfektion].}, journal = {Journal der Deutschen Dermatologischen Gesellschaft = Journal of the German Society of Dermatology : JDDG}, volume = {21}, number = {9}, pages = {1035-1037}, doi = {10.1111/ddg.15118_g}, pmid = {37700418}, issn = {1610-0387}, } @article {pmid37698628, year = {2023}, author = {Aly, A and Laszlo, ZI and Rajkumar, S and Demir, T and Hindley, N and Lamont, DJ and Lehmann, J and Seidel, M and Sommer, D and Franz-Wachtel, M and Barletta, F and Heumos, S and Czemmel, S and Kabashi, E and Ludolph, A and Boeckers, TM and Henstridge, CM and Catanese, A}, title = {Correction to: Integrative proteomics highlight presynaptic alterations and c-Jun misactivation as convergent pathomechanisms in ALS.}, journal = {Acta neuropathologica}, volume = {146}, number = {5}, pages = {783}, doi = {10.1007/s00401-023-02630-9}, pmid = {37698628}, issn = {1432-0533}, } @article {pmid37698313, year = {2023}, author = {Abraham, A and Abramovich, B and Banon, T and Weil, C and Chodick, G and Birman, N and Fainmesser, Y and Drory, VE}, title = {Pre-morbid Laboratory Tests, Diseases, and Medications in Amyotrophic Lateral Sclerosis in Israel.}, journal = {The Israel Medical Association journal : IMAJ}, volume = {25}, number = {9}, pages = {617-621}, pmid = {37698313}, issn = {1565-1088}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/drug therapy/epidemiology ; Israel/epidemiology ; *Cardiovascular Diseases ; Morbidity ; Antiviral Agents ; }, abstract = {BACKGROUND: There is an unmet need for real-world data regarding laboratory results, co-morbidities, and medication use prior to the first symptoms of amyotrophic lateral sclerosis (ALS). Researchers must identify specific subpopulations at risk for developing ALS and understand pathogenic mechanisms preceding the clinical presentation of ALS as well as possible subclinical disease manifestations.

OBJECTIVES: To valuate the role of laboratory results, co-morbidities, and medication use prior to the first symptoms of patients with ALS in Israel so that specific subpopulations at risk for developing ALS can be identified and for possible subclinical disease manifestations. To understand pathogenic mechanisms preceding the clinical presentation of ALS.

METHODS: At the ALS clinic at Tel Aviv Sourasky Medical Center, 259 ALS patients insured by Maccabi Healthcare Services and seen between January 1998 and December 2017 were included. Comparisons of demographics, co-morbidities, medications taken, history of trauma, and laboratory tests prior to disease onset were performed between patients and 1295 matched controls.

RESULTS: Prior to disease presentation, ALS patients had a higher frequency of hypertension and cardiovascular disease; presented more frequently with trauma and viral infections; more frequently used analgesics, non-steroidal anti-inflammatory drugs, narcotics, antibiotics, and antiviral medications; and had higher creatine kinase levels.

CONCLUSIONS: ALS patients showed higher frequency of cardiovascular disease prior to diagnosis, as well as higher frequency of trauma, infections, and pain medication usage.}, } @article {pmid37697342, year = {2023}, author = {Li, Z and Wang, X and Wang, X and Yi, X and Wong, YK and Wu, J and Xie, F and Hu, D and Wang, Q and Wang, J and Zhong, T}, title = {Research progress on the role of extracellular vesicles in neurodegenerative diseases.}, journal = {Translational neurodegeneration}, volume = {12}, number = {1}, pages = {43}, pmid = {37697342}, issn = {2047-9158}, mesh = {Humans ; *Neurodegenerative Diseases/diagnosis/therapy ; *Extracellular Vesicles ; *Alzheimer Disease ; *Parkinson Disease ; *Amyotrophic Lateral Sclerosis ; }, abstract = {Neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease, affect millions of people worldwide. Tremendous efforts have been put into disease-related research, but few breakthroughs have been made in diagnostic and therapeutic approaches. Extracellular vesicles (EVs) are heterogeneous cell-derived membrane structures that arise from the endosomal system or are directly separated from the plasma membrane. EVs contain many biomolecules, including proteins, nucleic acids, and lipids, which can be transferred between different cells, tissues, or organs, thereby regulating cross-organ communication between cells during normal and pathological processes. Recently, EVs have been shown to participate in various aspects of neurodegenerative diseases. Abnormal secretion and levels of EVs are closely related to the pathogenesis of neurodegenerative diseases and contribute to disease progression. Numerous studies have proposed EVs as therapeutic targets or biomarkers for neurodegenerative diseases. In this review, we summarize and discuss the advanced research progress on EVs in the pathological processes of several neurodegenerative diseases. Moreover, we outline the latest research on the roles of EVs in neurodegenerative diseases and their therapeutic potential for the diseases.}, } @article {pmid37696852, year = {2023}, author = {Latallo, MJ and Wang, S and Dong, D and Nelson, B and Livingston, NM and Wu, R and Zhao, N and Stasevich, TJ and Bassik, MC and Sun, S and Wu, B}, title = {Single-molecule imaging reveals distinct elongation and frameshifting dynamics between frames of expanded RNA repeats in C9ORF72-ALS/FTD.}, journal = {Nature communications}, volume = {14}, number = {1}, pages = {5581}, pmid = {37696852}, issn = {2041-1723}, support = {R01 GM136897/GM/NIGMS NIH HHS/United States ; R21 AG072078/AG/NIA NIH HHS/United States ; T32 GM007445/GM/NIGMS NIH HHS/United States ; T32 GM008403/GM/NIGMS NIH HHS/United States ; R01 NS107347/NS/NINDS NIH HHS/United States ; RF1 NS113820/NS/NINDS NIH HHS/United States ; T32 GM135131/GM/NIGMS NIH HHS/United States ; RF1 NS127925/NS/NINDS NIH HHS/United States ; }, mesh = {Humans ; *Frontotemporal Dementia/genetics ; *Amyotrophic Lateral Sclerosis/genetics ; C9orf72 Protein/genetics ; RNA/genetics ; Single Molecule Imaging ; Dipeptides ; Carrier Proteins ; }, abstract = {C9ORF72 hexanucleotide repeat expansion is the most common genetic cause of both amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). One pathogenic mechanism is the accumulation of toxic dipeptide repeat (DPR) proteins like poly-GA, GP and GR, produced by the noncanonical translation of the expanded RNA repeats. However, how different DPRs are synthesized remains elusive. Here, we use single-molecule imaging techniques to directly measure the translation dynamics of different DPRs. Besides initiation, translation elongation rates vary drastically between different frames, with GP slower than GA and GR the slowest. We directly visualize frameshift events using a two-color single-molecule translation assay. The repeat expansion enhances frameshifting, but the overall frequency is low. There is a higher chance of GR-to-GA shift than in the reversed direction. Finally, the ribosome-associated protein quality control (RQC) factors ZNF598 and Pelota modulate the translation dynamics, and the repeat RNA sequence is important for invoking the RQC pathway. This study reveals that multiple translation steps modulate the final DPR production. Understanding repeat RNA translation is critically important to decipher the DPR-mediated pathogenesis and identify potential therapeutic targets in C9ORF72-ALS/FTD.}, } @article {pmid37696099, year = {2023}, author = {Wiesenfarth, M and Huppertz, HJ and Dorst, J and Lulé, D and Ludolph, AC and Müller, HP and Kassubek, J}, title = {Structural and microstructural neuroimaging signature of C9orf72-associated ALS: A multiparametric MRI study.}, journal = {NeuroImage. Clinical}, volume = {39}, number = {}, pages = {103505}, pmid = {37696099}, issn = {2213-1582}, mesh = {Humans ; *Multiparametric Magnetic Resonance Imaging ; Diffusion Tensor Imaging ; C9orf72 Protein/genetics ; *Amyotrophic Lateral Sclerosis/diagnostic imaging/genetics ; Neuroimaging ; }, abstract = {BACKGROUND: ALS patients with hexanucleotide expansion in C9orf72 are characterized by a specific clinical phenotype, including more aggressive disease course and cognitive decline. Computerized multiparametric MRI with gray matter volumetry and diffusion tensor imaging (DTI) to analyze white matter structural connectivity is a potential in vivo biomarker.

OBJECTIVE: The objective of this study was to develop a multiparametric MRI signature in a large cohort of ALS patients with C9orf72 mutations. The aim was to investigate how morphological features of C9orf72-associated ALS differ in structural MRI and DTI compared to healthy controls and ALS patients without C9orf72 mutations.

METHODS: Atlas-based volumetry (ABV) and whole brain-based DTI-based analyses were performed in a cohort of n = 51 ALS patients with C9orf72 mutations and compared with both n = 51 matched healthy controls and n = 51 C9orf72 negative ALS patients, respectively. Subsequently, Spearman correlation analysis of C9orf72 ALS patients' data with clinical parameters (age of onset, sex, ALS-FRS-R, progression rate, survival) as well as ECAS and p-NfH in CSF was performed.

RESULTS: The whole brain voxel-by-voxel comparison of fractional anisotropy (FA) maps between C9orf72 ALS patients and controls showed significant bilateral alterations in axonal structures of the white matter at group level, primarily along the corticospinal tracts and in fibers projecting to the frontal lobes. For the frontal lobes, these alterations were also significant between C9orf72 positive and C9orf72 negative ALS patients. In ABV, patients with C9orf72 mutations showed lower volumes of the frontal, temporal, and parietal lobe, with the lowest values in the gray matter of the superior frontal and the precentral gyrus, but also in hippocampi and amygdala. Compared to C9orf72 negative ALS, the differences were shown to be significant for cerebral gray matter (p = 0.04), especially in the frontal (p = 0.01) and parietal lobe (p = 0.01), and in the thalamus (p = 0.004). A correlation analysis between ECAS and averaged regional FA values revealed significant correlations between cognitive performance in ECAS and frontal association fibers. Lower FA values in the frontal lobes were associated with worse performance in all cognitive domains measured (language, verbal fluency, executive functions, memory and spatial perception). In addition, there were significant negative correlations between age of onset and atlas-based volumetry results for gray matter.

CONCLUSIONS: This study demonstrates a distinct pattern of DTI alterations of the white matter and ubiquitous volume reductions of the gray matter early in the disease course of C9orf72-associated ALS. Alterations were closely linked to a more aggressive cognitive phenotype. These results are in line with an expected pTDP43 propagation pattern of cortical affection and thus strengthen the hypothesis that an underlying developmental disorder is present in ALS with C9orf72 expansions. Thus, multiparametric MRI could contribute to the assessment of the disease as an in vivo biomarker even in the early phase of the disease.}, } @article {pmid37695947, year = {2024}, author = {Sanson, G and Antonaglia, V and Buttignon, G and Caggegi, GD and Pegani, C and Peratoner, A}, title = {Dynamic Course of Clinical State Transitions in Patients Undergoing Advanced Life Support after Out-of-Hospital Cardiac Arrest.}, journal = {Prehospital emergency care}, volume = {28}, number = {3}, pages = {461-469}, doi = {10.1080/10903127.2023.2258192}, pmid = {37695947}, issn = {1545-0066}, mesh = {Humans ; *Out-of-Hospital Cardiac Arrest/therapy/complications ; *Cardiopulmonary Resuscitation ; Retrospective Studies ; *Emergency Medical Services ; Ventricular Fibrillation/therapy/complications ; *Tachycardia, Ventricular/complications ; Arrhythmias, Cardiac ; }, abstract = {OBJECTIVES: Studies of out-of-hospital cardiac arrest generally document the presenting (pulseless electrical activity [PEA], ventricular fibrillation/tachycardia (VF/VT), asystole), and the final states (resuming stable spontaneous circulation [s-ROSC], being declared dead). Only a few studies described the transitions between clinical states during advanced life support (ALS). The aim of this study was to describe and analyze the dynamics of state transitions during ALS.

METHODS: A retrospective analysis of 464 OHCA events was conducted. Any observed state and its corresponding changing time were documented through continuous electrocardiographic and trans-thoracic impedance recording.

RESULTS: When achieved, most s-ROSCs were obtained by 30 min, regardless of the presenting state. After this time point, the persistence of any transient state was associated with a great probability of being declared dead. The most probable change for VF/VT or PEA at any time was the transition to asystole (36.4% and 34.4%, respectively); patients in asystole at any time had a 70% probability of death. Patients achieving s-ROSC mostly came from a VF/VT state.In most cases, the presenting rhythm tended to persist over time during ALS. Asystole was the most stable state; a higher degree of instability was observed when the presenting rhythms were VF/VT or PEA. Transient ROSC episodes occurred mainly as the first transition after the presenting state, especially for initial PEA.

CONCLUSIONS: An understanding of the dynamic course of clinical state transitions during ALS may allow treatment strategies to be tailored in patients affected by OHCA.}, } @article {pmid37695732, year = {2023}, author = {Barasa, L and Chaudhuri, S and Zhou, JY and Jiang, Z and Choudhary, S and Green, RM and Wiggin, E and Cameron, M and Humphries, F and Fitzgerald, KA and Thompson, PR}, title = {Development of LB244, an Irreversible STING Antagonist.}, journal = {Journal of the American Chemical Society}, volume = {145}, number = {37}, pages = {20273-20288}, pmid = {37695732}, issn = {1520-5126}, support = {R35 GM118112/GM/NIGMS NIH HHS/United States ; }, mesh = {Humans ; Proteome ; *Amyotrophic Lateral Sclerosis ; *Autoimmune Diseases of the Nervous System ; Cyclic GMP ; Nucleotidyltransferases ; }, abstract = {The cGMP-AMP Synthase (cGAS)-Stimulator of Interferon Genes (STING) pathway plays a critical role in sensing dsDNA localized to the cytosol, resulting in the activation of a robust inflammatory response. While cGAS-STING signaling is essential for antiviral immunity, aberrant STING activation is observed in amyotrophic lateral sclerosis (ALS), lupus, and autoinflammatory diseases such as Aicardi-Goutières syndrome (AGS) and STING associated vasculopathy with onset in infancy (SAVI). Significant efforts have therefore focused on the development of STING inhibitors. In a concurrent submission, we reported that BB-Cl-amidine inhibits STING-dependent signaling in the nanomolar range, both in vitro and in vivo. Considering this discovery, we sought to generate analogs with higher potency and proteome-wide selectivity. Herein, we report the development of LB244, which displays nanomolar potency and inhibits STING signaling with markedly enhanced proteome-wide selectivity. Moreover, LB244 mirrored the efficacy of BB-Cl-amidine in vivo. In summary, our data identify novel chemical entities that inhibit STING signaling and provide a scaffold for the development of therapeutics for treating STING-dependent inflammatory diseases.}, } @article {pmid37695623, year = {2023}, author = {Genge, A and van den Berg, LH and Frick, G and Han, S and Abikoff, C and Simmons, A and Lin, Q and Patra, K and Kupperman, E and Berry, JD}, title = {Efficacy and Safety of Ravulizumab, a Complement C5 Inhibitor, in Adults With Amyotrophic Lateral Sclerosis: A Randomized Clinical Trial.}, journal = {JAMA neurology}, volume = {80}, number = {10}, pages = {1089-1097}, pmid = {37695623}, issn = {2168-6157}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy ; Male ; Female ; *Antibodies, Monoclonal, Humanized/therapeutic use/adverse effects/administration & dosage ; Middle Aged ; Double-Blind Method ; Aged ; Adult ; Complement Inactivating Agents/therapeutic use/adverse effects/administration & dosage ; Treatment Outcome ; Complement C5/antagonists & inhibitors ; }, abstract = {IMPORTANCE: Additional therapies for amyotrophic lateral sclerosis (ALS) are urgently needed. Immune-mediated complement activation may be involved in ALS pathogenesis as evidenced by the upregulation of terminal components; thus, complement inhibition could potentially slow progression.

OBJECTIVE: To evaluate the safety and efficacy of the terminal complement C5 inhibitor ravulizumab in adults with ALS.

This double-blind, placebo-controlled, parallel-group, multinational, randomized, phase 3 clinical trial was conducted from March 30, 2020, to October 17, 2021, in 81 ALS specialty centers across 17 countries. A preplanned, unmasked, nonbinding interim futility analysis was conducted when 33% of participants had completed week 26, wherein a conditional power of less than 10% would halt the trial. A total of 478 individuals were screened, and 96 were excluded. Inclusion criteria were weight of 40 kg or more, fulfillment of the El Escorial diagnostic criteria, and a minimal prestudy Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) progression score of -0.3 points per month.

INTERVENTIONS: Study treatment consisted of placebo or a weight-based dose of intravenous ravulizumab every 8 weeks until week 42. Participants could continue standard-of-care treatment.

MAIN OUTCOMES AND MEASURES: The primary end point was change from baseline in ALSFRS-R score at week 50 based on the Combined Assessment of Function and Survival (CAFS).

RESULTS: A total of 382 participants were randomly assigned 2:1 to receive ravulizumab (n = 255; mean [SD] age, 58.6 [10.6] years; 94 female [36.9%] and 161 male [63.1%]) or placebo (n = 127; mean [SD] age, 58.0 [11.0] years; 58 female [45.7%] and 69 male [54.3%]). The interim analysis showed that the observed mean change from baseline in ALSFRS-R at week 50 was -14.67 points (SE, 0.89 points; 95% CI, -16.42 to -12.91 points) for ravulizumab and -13.33 points (SE, 1.22 points; 95% CI, -15.72 to -10.93 points) for placebo, with no significant difference between the groups (mean [SE] difference, -1.34 [1.46] points; 95% CI, -4.21 to 1.53 points). Based on these data, the trial was terminated for futility. The primary analysis at week 50 showed no significant difference in CAFS between groups (mean [SE], 5.5 [10.8] points; 95% CI, -15.7 to 26.6 points; P = .61). Overall incidence rates for treatment-emergent adverse events were similar for ravulizumab (204 participants [80.0%]) and placebo (108 participants [85.0%]).

CONCLUSIONS AND RELEVANCE: This trial rapidly showed that terminal complement C5 inhibition with ravulizumab did not slow functional decline in participants with ALS and that the safety profiles of ravulizumab and placebo were similar. Highly effective, novel treatments are critically needed to slow functional decline and extend survival in patients with ALS.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04248465.}, } @article {pmid37695446, year = {2024}, author = {Yang, EJ}, title = {Combined Treatment with Bojungikgi-tang (Buzhong Yiqi Decoction) and Riluzole Attenuates Cell Death in TDP-43-Expressing Cells.}, journal = {Chinese journal of integrative medicine}, volume = {30}, number = {7}, pages = {616-622}, pmid = {37695446}, issn = {1993-0402}, mesh = {*Drugs, Chinese Herbal/pharmacology ; *DNA-Binding Proteins/metabolism ; *Cell Death/drug effects ; *Riluzole/pharmacology ; Cell Line ; Autophagy/drug effects ; Animals ; Amyotrophic Lateral Sclerosis/drug therapy/pathology/metabolism ; Cell Survival/drug effects ; Drug Therapy, Combination ; Humans ; }, abstract = {OBJECTIVE: To examine the effect of combined treatment with Bojungikgi-tang (BJIGT, Buzhong Yiqi Decoction) and riluzole (RZ) in transactive response DNA-binding protein 43 (TDP-43) stress granule (SG) cells, a amyotrophic lateral sclerosis (ALS) cell line using transcriptomic and molecular techniques.

METHODS: TDP-43 SG cells were pretreated with BJIGT (100 µg/mL), RZ (50 µmol/L), and combined BJIGT (100 µg/mL)/RZ (50 µmol/L) for 6 h before treatment with lipopolysaccharide (LPS, 200 µmol/L). Cell viability assay was performed to elucidate cell toxicity in TDP-43 SC cells using a cell-counting kit-8 (CCK8) assay kit. The expression levels of cell death-related proteins, including Bax, caspase 1, cleaved caspase 3 and DJ1 in TDP-43 SG cells were examined by Western blot analysis. The autophagy-related proteins, including pmTOR/mTOR, LC3b, P62, ATG7 and Bcl-2-associated athanogene 3 (Bag3) were investigated using immunofluorescence and immunoblotting assays.

RESULTS: Cell viability assay and Western blot analysis showed that combined treatment with BJIGT and RZ suppressed LPS-induced cell death and expression of cell death-related proteins, including Bax, caspase 1, and DJ1 (P<0.05 or P<0.01). Immunofluorescence and immunoblotting assays showed that combined treatment with BJIGT and RZ reduced LPS-induced formation of TDP-43 aggregates and regulated autophagy-related protein levels, including p62, light chain 3b, Bag3, and ATG7, in TDP-43-expressing cells (P<0.05 or P<0.01).

CONCLUSION: The combined treatment of BJIGT and RZ might reduce inflammation and regulate autophagy dysfunction in TDP-43-induced ALS.}, } @article {pmid37694825, year = {2023}, author = {Tahedl, M and Tan, EL and Chipika, RH and Lope, J and Hengeveld, JC and Doherty, MA and McLaughlin, RL and Hardiman, O and Hutchinson, S and McKenna, MC and Bede, P}, title = {The involvement of language-associated networks, tracts, and cortical regions in frontotemporal dementia and amyotrophic lateral sclerosis: Structural and functional alterations.}, journal = {Brain and behavior}, volume = {13}, number = {11}, pages = {e3250}, pmid = {37694825}, issn = {2162-3279}, mesh = {Humans ; *Frontotemporal Dementia/diagnostic imaging/genetics/pathology ; *Amyotrophic Lateral Sclerosis/diagnostic imaging/genetics ; C9orf72 Protein/genetics ; Brain/pathology ; Language ; }, abstract = {BACKGROUND: Language deficits are cardinal manifestations of some frontotemporal dementia (FTD) phenotypes and also increasingly recognized in sporadic and familial amyotrophic lateral sclerosis (ALS). They have considerable social and quality-of-life implications, and adaptive strategies are challenging to implement. While the neuropsychological profiles of ALS-FTD phenotypes are well characterized, the neuronal underpinnings of language deficits are less well studied.

METHODS: A multiparametric, quantitative neuroimaging study was conducted to characterize the involvement of language-associated networks, tracts, and cortical regions with a panel of structural, diffusivity, and functional magnetic resonance imaging (MRI) metrics. Seven study groups were evaluated along the ALS-FTD spectrum: healthy controls (HC), individuals with ALS without cognitive impairment (ALSnci), C9orf72-negative ALS-FTD, C9orf72-positive ALS-FTD, behavioral-variant FTD (bvFTD), nonfluent variant primary progressive aphasia (nfvPPA), and semantic variant PPA (svPPA). The integrity of the Broca's area, Wernicke's area, frontal aslant tract (FAT), arcuate fascicle (AF), inferior occipitofrontal fascicle (IFO), inferior longitudinal fascicle (ILF), superior longitudinal fascicle (SLF), and uncinate fascicle (UF) was quantitatively evaluated. The functional connectivity (FC) between Broca's and Wernicke' areas and FC along the FAT was also specifically assessed.

RESULTS: Patients with nfvPPA and svPPA exhibit distinctive patterns of gray and white matter degeneration in language-associated brain regions. Individuals with bvFTD exhibit Broca's area, right FAT, right IFO, and UF degeneration. The ALSnci group exhibits Broca's area atrophy and decreased FC along the FAT. Both ALS-FTD cohorts, irrespective of C9orf72 status, show bilateral FAT, AF, and IFO pathology. Interestingly, only C9orf72-negative ALS-FTD patients exhibit bilateral uncinate and right ILF involvement, while C9orf72-positive ALS-FTD patients do not.

CONCLUSIONS: Language-associated tracts and networks are not only affected in language-variant FTD phenotypes but also in ALS and bvFTD. Language domains should be routinely assessed in ALS irrespective of the genotype.}, } @article {pmid37694369, year = {2023}, author = {Verde, F and Aiello, EN and Adobbati, L and Poletti, B and Solca, F and Tiloca, C and Sangalli, D and Maranzano, A and Muscio, C and Ratti, A and Zago, S and Ticozzi, N and Frisoni, GB and Silani, V}, title = {Coexistence of Amyotrophic Lateral Sclerosis and Alzheimer's Disease: Case Report and Review of the Literature.}, journal = {Journal of Alzheimer's disease : JAD}, volume = {95}, number = {4}, pages = {1383-1399}, doi = {10.3233/JAD-230562}, pmid = {37694369}, issn = {1875-8908}, mesh = {Humans ; Female ; Male ; *Amyotrophic Lateral Sclerosis/complications/diagnosis/genetics ; *Alzheimer Disease/diagnosis/diagnostic imaging ; *Cognitive Dysfunction/complications ; Brain/diagnostic imaging ; *Frontotemporal Dementia/complications/diagnostic imaging/genetics ; }, abstract = {We describe a case of amyotrophic lateral sclerosis (ALS) associated with Alzheimer's disease (AD) and review the literature about the coexistence of the two entities, highlighting the following: mean age at onset is 63.8 years, with slight female predominance; ALS tends to manifest after cognitive impairment and often begins in the bulbar region; average disease duration is 3 years; cognitive phenotype is mostly amnestic; the pattern of brain involvement is, in most cases, consistent with AD. Our case and the reviewed ones suggest that patients with ALS and dementia lacking unequivocal features of FTD should undergo additional examinations in order to recognize AD.}, } @article {pmid37694126, year = {2023}, author = {Liguori, F and Pandey, UB and Digilio, FA}, title = {Editorial: Drosophila as a model to study neurodegenerative diseases.}, journal = {Frontiers in neuroscience}, volume = {17}, number = {}, pages = {1275253}, pmid = {37694126}, issn = {1662-4548}, } @article {pmid37693725, year = {2023}, author = {Barbalho, IMP and Fonseca, ALA and Fernandes, F and Henriques, J and Gil, P and Nagem, D and Lindquist, R and Lima, T and Dos Santos, JPQ and Paiva, J and Morais, AHF and Dourado Júnior, MET and Valentim, RAM}, title = {Digital health solution for monitoring and surveillance of Amyotrophic Lateral Sclerosis in Brazil.}, journal = {Frontiers in public health}, volume = {11}, number = {}, pages = {1209633}, pmid = {37693725}, issn = {2296-2565}, mesh = {Humans ; Brazil/epidemiology ; *Amyotrophic Lateral Sclerosis/epidemiology ; *Neurodegenerative Diseases ; Databases, Factual ; Health Personnel ; }, abstract = {Amyotrophic Lateral Sclerosis (ALS) is a complex and rare neurodegenerative disease given its heterogeneity. Despite being known for many years, few countries have accurate information about the characteristics of people diagnosed with ALS, such as data regarding diagnosis and clinical features of the disease. In Brazil, the lack of information about ALS limits data for the research progress and public policy development that benefits people affected by this health condition. In this context, this article aims to show a digital health solution development and application for research, intervention, and strengthening of the response to ALS in the Brazilian Health System. The proposed solution is composed of two platforms: the Brazilian National ALS Registry, responsible for the data collection in a structured way from ALS patients all over Brazil; and the Brazilian National ALS Observatory, responsible for processing the data collected in the National Registry and for providing a monitoring room with indicators on people diagnosed with ALS in Brazil. The development of this solution was supported by the Brazilian Ministry of Health (MoH) and was carried out by a multidisciplinary team with expertise in ALS. This solution represents a tool with great potential for strengthening public policies and stands out for being the only public database on the disease, besides containing innovations that allow data collection by health professionals and/or patients. By using both platforms, it is believed that it will be possible to understand the demographic and epidemiological data of ALS in Brazil, since the data will be able to be analyzed by care teams and also by public health managers, both in the individual and collective monitoring of people living with ALS in Brazil.}, } @article {pmid37693322, year = {2023}, author = {Bayraktar, E and Çiftçi, V and Uysal, H and Başak, AN}, title = {Another de novo mutation in the SOD1 gene: the first Turkish patient with SOD1-His47Arg, a case report.}, journal = {Frontiers in genetics}, volume = {14}, number = {}, pages = {1208673}, pmid = {37693322}, issn = {1664-8021}, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal, progressive neurodegenerative disease of motor neurons. Most ALS cases are considered sporadic due to the presence of a combination of environmental and complex genetic risk factors, while approximately 10% of cases have a family history. Pathogenic variants in the SOD1 gene are the second most frequent causative factor of genetics-based ALS worldwide, after C9ORF72 hexanucleotide repeat expansion. The De novo occurrence of pathogenic mutations in ALS-associated genes and its effect on disease progression have been studied previously, especially in the FUS gene. Recent studies have shown that a very small portion of SOD1 cases occurred de novo. Here, we present the first de novo case of the SOD1 His47Arg mutation in a young female patient with mild symptoms and, currently, a slow progression for 7 years.}, } @article {pmid37692101, year = {2023}, author = {Stansberry, WM and Pierchala, BA}, title = {Neurotrophic factors in the physiology of motor neurons and their role in the pathobiology and therapeutic approach to amyotrophic lateral sclerosis.}, journal = {Frontiers in molecular neuroscience}, volume = {16}, number = {}, pages = {1238453}, pmid = {37692101}, issn = {1662-5099}, support = {R01 NS089585/NS/NINDS NIH HHS/United States ; }, abstract = {The discovery of the neurotrophins and their potent survival and trophic effects led to great enthusiasm about their therapeutic potential to rescue dying neurons in neurodegenerative diseases. The further discovery that brain-derived neurotrophic factor (BDNF), ciliary neurotrophic factor (CNTF) and glial cell line-derived neurotrophic factor (GDNF) had potent survival-promoting activity on motor neurons led to the proposal for their use in motor neuron diseases such as amyotrophic lateral sclerosis (ALS). In this review we synthesize the literature pertaining to the role of NGF, BDNF, CNTF and GDNF on the development and physiology of spinal motor neurons, as well as the preclinical studies that evaluated their potential for the treatment of ALS. Results from the clinical trials of these molecules will also be described and, with the aid of decades of hindsight, we will discuss what can reasonably be concluded and how this information can inform future clinical development of neurotrophic factors for ALS.}, } @article {pmid37691335, year = {2023}, author = {Corcoran, J and Kluger, BM}, title = {Prognosis in chronic progressive neurologic disease: a narrative review.}, journal = {Annals of palliative medicine}, volume = {12}, number = {5}, pages = {952-962}, doi = {10.21037/apm-22-1338}, pmid = {37691335}, issn = {2224-5839}, mesh = {Humans ; *Parkinson Disease/diagnosis/therapy ; *Nervous System Diseases ; Prognosis ; Palliative Care ; Chronic Disease ; *Dementia ; }, abstract = {BACKGROUND AND OBJECTIVE: Prognostication is the process of predicting a patient's likely outcome from their medical condition, and consists of determining both how well and how long a patient may live. There are few disease-specific prognostic tools to estimate a patient's individualized prognosis in terms of symptom burden and mortality. Here we summarize relevant literature on prognosis in four progressive neurologic diseases-dementia, Parkinson's disease, amyotrophic lateral sclerosis, and multiple sclerosis-as well as on best practices on communicating prognosis with patients and care partners.

METHODS: We conducted a PubMed search for terms including "prognosis", "mortality" and "prognostic indicators" in addition to specific diseases, and for terms including "prognosis AND communication". Only English-language papers were included in this review. The time frame of our literature search was 1965 through March 1, 2023.

KEY CONTENT AND FINDINGS: There is some literature to help clinicians in predicting disease progression and survival. These include both general factors (e.g., age, medical co-morbidities) and disease-specific factors (e.g., postural instability in Parkinson's disease). There is also literature on communication of prognosis in neurologic and non-neurologic disease which demonstrates that many patients and care partners prefer to hear prognosis early after diagnosis and to have prognosis discussed as a roadmap of disease.

CONCLUSIONS: More work is needed to develop tools for individualized prognostication and communication for patients with neurologic disease. While there is limited literature on disease-specific prognostic models, existing literature combined with palliative care approaches may improve prognostic guidance for patients.}, } @article {pmid37691292, year = {2023}, author = {Roggenbuck, J and Eubank, BHF and Wright, J and Harms, MB and Kolb, SJ and , }, title = {Evidence-based consensus guidelines for ALS genetic testing and counseling.}, journal = {Annals of clinical and translational neurology}, volume = {10}, number = {11}, pages = {2074-2091}, pmid = {37691292}, issn = {2328-9503}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/genetics/therapy ; C9orf72 Protein/genetics ; Systematic Reviews as Topic ; Meta-Analysis as Topic ; Genetic Testing ; Counseling ; }, abstract = {OBJECTIVE: Advances in amyotrophic lateral sclerosis (ALS) gene discovery, ongoing gene therapy trials, and patient demand have driven increased use of ALS genetic testing. Despite this progress, the offer of genetic testing to persons with ALS is not yet "standard of care." Our primary goal is to develop clinical ALS genetic counseling and testing guidelines to improve and standardize genetic counseling and testing practice among neurologists, genetic counselors or any provider caring for persons with ALS.

METHODS: Core clinical questions were identified and a rapid review performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA-P) 2015 method. Guideline recommendations were drafted and the strength of evidence for each recommendation was assessed by combining two systems: the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) System and the Evaluation of Genomic Applications in Practice and Prevention (EGAPP). A modified Delphi approach was used to reach consensus among a group of content experts for each guideline statement.

RESULTS: A total of 35 guideline statements were developed. In summary, all persons with ALS should be offered single-step genetic testing, consisting of a C9orf72 assay, along with sequencing of SOD1, FUS, and TARDBP, at a minimum. The key education and genetic risk assessments that should be provided before and after testing are delineated. Specific guidance regarding testing methods and reporting for C9orf72 and other genes is provided for commercial laboratories.

INTERPRETATION: These evidence-based, consensus guidelines will support all stakeholders in the ALS community in navigating benefits and challenges of genetic testing.}, } @article {pmid37691199, year = {2024}, author = {Bhat, MA and Dhaneshwar, S}, title = {Neurodegenerative Diseases: New Hopes and Perspectives.}, journal = {Current molecular medicine}, volume = {24}, number = {8}, pages = {1004-1032}, pmid = {37691199}, issn = {1875-5666}, mesh = {Humans ; *Neurodegenerative Diseases/therapy/pathology ; Animals ; }, abstract = {Alzheimer's disease, Parkinson's disease, Amyotrophic lateral sclerosis, Huntington's disease, and Friedrich ataxia are all incurable neurodegenerative diseases defined by the continuous progressive loss of distinct neuronal subtypes. Despite their rising prevalence among the world's ageing population, fewer advances have been made in the concurrent massive efforts to develop newer drugs. Recently, there has been a shift in research focus towards the discovery of new therapeutic agents for neurodegenerative diseases. In this review, we have summarized the recently developed therapies and their status in the management of neurodegenerative diseases.}, } @article {pmid37689642, year = {2023}, author = {Bustamante-Barrientos, FA and Luque-Campos, N and Araya, MJ and Lara-Barba, E and de Solminihac, J and Pradenas, C and Molina, L and Herrera-Luna, Y and Utreras-Mendoza, Y and Elizondo-Vega, R and Vega-Letter, AM and Luz-Crawford, P}, title = {Mitochondrial dysfunction in neurodegenerative disorders: Potential therapeutic application of mitochondrial transfer to central nervous system-residing cells.}, journal = {Journal of translational medicine}, volume = {21}, number = {1}, pages = {613}, pmid = {37689642}, issn = {1479-5876}, mesh = {Humans ; Mitochondria ; *Neurodegenerative Diseases/therapy ; *Alzheimer Disease ; *Parkinson Disease ; Central Nervous System ; }, abstract = {Mitochondrial dysfunction is reiteratively involved in the pathogenesis of diverse neurodegenerative diseases. Current in vitro and in vivo approaches support that mitochondrial dysfunction is branded by several molecular and cellular defects, whose impact at different levels including the calcium and iron homeostasis, energetic balance and/or oxidative stress, makes it difficult to resolve them collectively given their multifactorial nature. Mitochondrial transfer offers an overall solution since it contains the replacement of damage mitochondria by healthy units. Therefore, this review provides an introducing view on the structure and energy-related functions of mitochondria as well as their dynamics. In turn, we summarize current knowledge on how these features are deregulated in different neurodegenerative diseases, including frontotemporal dementia, multiple sclerosis, amyotrophic lateral sclerosis, Friedreich ataxia, Alzheimer´s disease, Parkinson´s disease, and Huntington's disease. Finally, we analyzed current advances in mitochondrial transfer between diverse cell types that actively participate in neurodegenerative processes, and how they might be projected toward developing novel therapeutic strategies.}, } @article {pmid37689321, year = {2023}, author = {Donini, L and Tanel, R and Zuccarino, R and Basso, M}, title = {Protein biomarkers for the diagnosis and prognosis of Amyotrophic Lateral Sclerosis.}, journal = {Neuroscience research}, volume = {197}, number = {}, pages = {31-41}, doi = {10.1016/j.neures.2023.09.002}, pmid = {37689321}, issn = {1872-8111}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/metabolism ; Prognosis ; Biomarkers ; Disease Progression ; }, abstract = {Amyotrophic Lateral Sclerosis (ALS) is the most common motor neuron disease, still incurable. The disease is highly heterogenous both genetically and phenotypically. Therefore, developing efficacious treatments is challenging in many aspects because it is difficult to predict the rate of disease progression and stratify the patients to minimize statistical variability in clinical studies. Moreover, there is a lack of sensitive measures of therapeutic effect to assess whether a pharmacological intervention ameliorates the disease. There is also urgency of markers that reflect a molecular mechanism dysregulated by ALS pathology and can be rescued when a treatment relieves the condition. Here, we summarize and discuss biomarkers tested in multicentered studies and across different laboratories like neurofilaments, the most used marker in ALS clinical studies, neuroinflammatory-related proteins, p75[ECD], p-Tau/t-Tau, and UCHL1. We also explore the applicability of muscle proteins and extracellular vesicles as potential biomarkers.}, } @article {pmid37688751, year = {2023}, author = {Khakha, N and Khan, H and Kaur, A and Singh, TG}, title = {Therapeutic implications of phosphorylation- and dephosphorylation-dependent factors of cAMP-response element-binding protein (CREB) in neurodegeneration.}, journal = {Pharmacological reports : PR}, volume = {75}, number = {5}, pages = {1152-1165}, pmid = {37688751}, issn = {2299-5684}, mesh = {Animals ; *Alzheimer Disease/drug therapy ; Cyclic AMP Response Element-Binding Protein/metabolism ; *Neurodegenerative Diseases/drug therapy/genetics ; Phosphorylation ; Response Elements ; Humans ; }, abstract = {Neurodegeneration is a condition of the central nervous system (CNS) characterized by loss of neural structures and function. The most common neurodegenerative disorders (NDDs) include Alzheimer's disease (AD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), multiple sclerosis (MS), motor neuron disorders, psychological disorders, dementia with vascular dementia (VaD), Lewy body dementia (DLB), epilepsy, cerebral ischemia, mental illness, and behavioral disorders. CREB (cAMP-response element-binding protein) represent a nuclear protein that regulates gene transcriptional activity. The primary focus of the review pertains to the exploration of CREB expression and activation within the context of neurodegenerative diseases, specifically in relation to the phosphorylation and dephosphorylation events that occur within the CREB signaling pathway under normal physiological conditions. The findings mentioned have contributed to the elucidation of the regulatory mechanisms governing CREB activity. Additionally, they have provided valuable insights into the potential mediation of diverse biological processes, such as memory consolidation and neuroprotective effects, by various related studies. The promotion of synaptic plasticity and neurodevelopment in the central nervous system through the targeting of CREB proteins has the potential to contribute to the prevention or delay of the onset of neurodegenerative disorders. Multiple drugs have been found to initiate downstream signaling pathways, leading to neuroprotective advantages in both animal model studies and clinical trials. The clinical importance of the cAMP-response element-binding protein (CREB) is examined in this article, encompassing its utility as both a predictive/prognostic marker and a target for therapeutic interventions.}, } @article {pmid37688660, year = {2023}, author = {Yue, W and Tang, CW and Fang, Y}, title = {PIKFYVE Inhibition, A Neuronal "Emetic" for Treating ALS?.}, journal = {Neuroscience bulletin}, volume = {39}, number = {11}, pages = {1738-1740}, pmid = {37688660}, issn = {1995-8218}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy ; Neurons ; Phosphatidylinositol 3-Kinases ; *Phosphoinositide-3 Kinase Inhibitors/therapeutic use ; }, } @article {pmid37688479, year = {2024}, author = {Li, Z and Tian, M and Jia, H and Li, X and Liu, Q and Zhou, X and Li, R and Dong, H and Liu, Y}, title = {Genetic variation in targets of lipid-lowering drugs and amyotrophic lateral sclerosis risk: a Mendelian randomization study.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {25}, number = {1-2}, pages = {197-206}, doi = {10.1080/21678421.2023.2255622}, pmid = {37688479}, issn = {2167-9223}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy/epidemiology/genetics ; Mendelian Randomization Analysis ; Genome-Wide Association Study ; Cholesterol, LDL ; Apolipoproteins B/genetics ; Genetic Variation ; Polymorphism, Single Nucleotide/genetics ; }, abstract = {BACKGROUND: The use of lipid-lowering drugs is still highly controversial in patients with amyotrophic lateral sclerosis (ALS). We performed a drug-target Mendelian randomization (MR) analysis to investigate the effect of targeted lipid-lowering drugs on the risk of ALS.

METHODS: First, we evaluated the causal relationship between HMG-CoA (3-hydroxy-3-methylglutaryl coenzyme A) reductase (HMGCR) inhibitors-taking trait and ALS using a bidirectional two-sample MR study. Second, we investigated the causal relationship between lipid-lowering drugs and ALS through a drug-target MR approach. The summary data for HMGCR inhibitors-taking traits were extracted from a genome-wide association study (GWAS) of medication use and associated disease in the UK Biobank. The summary data for low-density lipoprotein cholesterol and apolipoprotein B (apoB) were extracted from a meta-analysis of GWAS in individuals of European ancestry in the UKB. The GWAS summary data of ALS were obtained from the Project MinE.

RESULTS: Our bidirectional two-sample MR showed that genetically determined increased HMGCR inhibitors-taking trait was an independent risk factor for ALS (odds ratio [OR] = 1.090, 95% confidence interval [CI] = 1.035-1.150, p = 0.001). The results of drug-target MR showed that the increased expression of the HMGCR gene in blood with the higher risk of ALS (OR = 1.21, 95% CI = 1.01-1.46; p = 0.042) through SMR method and the apoB level mediated by the APOB gene increased the risk of ALS (OR = 1.15; 95% CI =1.05-1.25; p = 0.001) through inverse-variance weighted MR method.

CONCLUSION: This present study provides genetic support for a positive causal effect of HMGCR inhibitors-taking trait and ALS. The reason for this may be due to the underlying disease condition behind the medication, rather than the medication itself. Our findings also suggested that HMGCR and apoB inhibitors may have potential protective effects on ALS.}, } @article {pmid37687832, year = {2023}, author = {Pavelka, K and Matoušková, E and Pavelka, K}, title = {Remarks on Geomatics Measurement Methods Focused on Forestry Inventory.}, journal = {Sensors (Basel, Switzerland)}, volume = {23}, number = {17}, pages = {}, pmid = {37687832}, issn = {1424-8220}, abstract = {This contribution focuses on a comparison of modern geomatics technologies for the derivation of growth parameters in forest management. The present text summarizes the results of our measurements over the last five years. As a case project, a mountain spruce forest with planned forest logging was selected. In this locality, terrestrial laser scanning (TLS) and terrestrial and drone close-range photogrammetry were experimentally used, as was the use of PLS mobile technology (personal laser scanning) and ALS (aerial laser scanning). Results from the data joining, usability, and economics of all technologies for forest management and ecology were discussed. ALS is expensive for small areas and the results were not suitable for a detailed parameter derivation. The RPAS (remotely piloted aircraft systems, known as "drones") method of data acquisition combines the benefits of close-range and aerial photogrammetry. If the approximate height and number of the trees are known, one can approximately calculate the extracted cubage of wood mass before forest logging. The use of conventional terrestrial close-range photogrammetry and TLS proved to be inappropriate and practically unusable in our case, and also in standard forestry practice after consultation with forestry workers. On the other hand, the use of PLS is very simple and allows you to quickly define ordered parameters and further calculate, for example, the cubic volume of wood stockpiles. The results from our research into forestry show that drones can be used to estimate quantities (wood cubature) and inspect the health status of spruce forests, However, PLS seems, nowadays, to be the best solution in forest management for deriving forest parameters. Our results are mainly oriented to practice and in no way diminish the general research in this area.}, } @article {pmid37686737, year = {2023}, author = {Zhou, J and Zhang, W and Cao, Z and Lian, S and Li, J and Nie, J and Huang, Y and Zhao, K and He, J and Liu, C}, title = {Association of Selenium Levels with Neurodegenerative Disease: A Systemic Review and Meta-Analysis.}, journal = {Nutrients}, volume = {15}, number = {17}, pages = {}, pmid = {37686737}, issn = {2072-6643}, support = {81903294//National Natural Science Foundation of China/ ; 202102020120//Guangzhou Basic and Applied Basic Research Foundation/ ; A2022080//Medical Scientific Research Foundation of Guangdong Province of China/ ; }, mesh = {Humans ; *Selenium ; *Neurodegenerative Diseases ; *Alzheimer Disease ; *Amyotrophic Lateral Sclerosis ; Databases, Factual ; }, abstract = {BACKGROUND: Neurodegenerative diseases (NDs) have posed significant challenges to public health, and it is crucial to understand their mechanisms in order to develop effective therapeutic strategies. Recent studies have highlighted the potential role of selenium in ND pathogenesis, as it plays a vital role in maintaining cellular homeostasis and preventing oxidative damage. However, a comprehensive analysis of the association between selenium and NDs is still lacking.

METHOD: Five public databases, namely PubMed, Web of Science, EMBASE, Cochrane and Clinical Trials, were searched in our research. Random model effects were chosen, and Higgins inconsistency analyses (I[2]), Cochrane's Q test and Tau2 were calculated to evaluate the heterogeneity.

RESULT: The association of selenium in ND patients with Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS) and Huntington's disease (HD) was studied. A statistically significant relationship was only found for AD patients (SMD = -0.41, 95% CI (-0.64, -0.17), p < 0.001), especially for erythrocytes. However, no significant relationship was observed in the analysis of the other four diseases.

CONCLUSION: Generally, this meta-analysis indicated that AD patients are strongly associated with lower selenium concentrations compared with healthy people, which may provide a clinical reference in the future. However, more studies are urgently needed for further study and treatment of neurodegenerative diseases.}, } @article {pmid37686322, year = {2023}, author = {Badu-Mensah, A and Guo, X and Mendez, R and Parsaud, H and Hickman, JJ}, title = {The Effect of Skeletal Muscle-Specific Creatine Treatment on ALS NMJ Integrity and Function.}, journal = {International journal of molecular sciences}, volume = {24}, number = {17}, pages = {}, pmid = {37686322}, issn = {1422-0067}, support = {R01 NS050452/NS/NINDS NIH HHS/United States ; R01NS050452/NH/NIH HHS/United States ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy ; *Creatine/pharmacology/therapeutic use ; Muscle Fatigue ; Muscle, Skeletal ; Neuromuscular Junction ; }, abstract = {Although skeletal muscle (hSKM) has been proven to be actively involved in Amyotrophic Lateral Sclerosis (ALS) neuromuscular junction (NMJ) dysfunction, it is rarely considered as a pharmacological target in preclinical drug discovery. This project investigated how improving ALS hSKM viability and function effects NMJ integrity. Phenotypic ALS NMJ human-on-a-chip models developed from patient-derived induced pluripotent stem cells (iPSCs) were used to study the effect of hSKM-specific creatine treatment on clinically relevant functional ALS NMJ parameters, such as NMJ numbers, fidelity, stability, and fatigue index. Results indicated comparatively enhanced NMJ numbers, fidelity, and stability, as well as reduced fatigue index, across all hSKM-specific creatine-treated systems. Immunocytochemical analysis of the NMJs also revealed improved post-synaptic nicotinic Acetylcholine receptor (AChR) clustering and cluster size in systems supplemented with creatine relative to the un-dosed control. This work strongly suggests hSKM as a therapeutic target in ALS drug discovery. It also demonstrates the need to consider all tissues involved in multi-systemic diseases, such as ALS, in drug discovery efforts. Finally, this work further establishes the BioMEMs NMJ platform as an effective means of performing mutation-specific drug screening, which is a step towards personalized medicine for rare diseases.}, } @article {pmid37686239, year = {2023}, author = {Zalar, M and Wang, B and Plavec, J and Šket, P}, title = {Insight into Tetramolecular DNA G-Quadruplexes Associated with ALS and FTLD: Cation Interactions and Formation of Higher-Ordered Structure.}, journal = {International journal of molecular sciences}, volume = {24}, number = {17}, pages = {}, pmid = {37686239}, issn = {1422-0067}, support = {P1-0242//Slovenian Research Agency/ ; J1-1704//Slovenian Research Agency/ ; J1-7108//Slovenian Research Agency/ ; }, mesh = {Humans ; *G-Quadruplexes ; *Amyotrophic Lateral Sclerosis/genetics ; *Frontotemporal Dementia ; *Frontotemporal Lobar Degeneration ; Cations ; Potassium ; }, abstract = {The G4C2 hexanucleotide repeat expansion in the c9orf72 gene is a major genetic cause of familial amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD), with the formation of G-quadruplexes directly linked to the development of these diseases. Cations play a crucial role in the formation and structure of G-quadruplexes. In this study, we investigated the impact of biologically relevant potassium ions on G-quadruplex structures and utilized [15]N-labeled ammonium cations as a substitute for K[+] ions to gain further insights into cation binding and exchange dynamics. Through nuclear magnetic resonance spectroscopy and molecular dynamics simulations, we demonstrate that the single d(G4C2) repeat, in the presence of [15]NH4[+] ions, adopts a tetramolecular G-quadruplex with an all-syn quartet at the 5'-end. The movement of [15]NH4[+] ions through the central channel of the G-quadruplex, as well as to the bulk solution, is governed by the vacant cation binding site, in addition to the all-syn quartet at the 5'-end. Furthermore, the addition of K[+] ions to G-quadruplexes folded in the presence of [15]NH4[+] ions induces stacking of G-quadruplexes via their 5'-end G-quartets, leading to the formation of stable higher-ordered species.}, } @article {pmid37683919, year = {2023}, author = {Yu, Z and Zhang, H and Wang, Y}, title = {Cervical Spondylotic Amyotrophy Initially Misdiagnosed as Amyotrophic Lateral Sclerosis.}, journal = {World neurosurgery}, volume = {180}, number = {}, pages = {3-5}, doi = {10.1016/j.wneu.2023.08.130}, pmid = {37683919}, issn = {1878-8769}, mesh = {Male ; Humans ; Middle Aged ; *Amyotrophic Lateral Sclerosis/diagnosis ; Muscular Atrophy/diagnosis/surgery ; Muscle, Skeletal ; Muscle Weakness/etiology ; *Spondylosis/diagnostic imaging/surgery ; Diagnostic Errors ; Cervical Vertebrae/diagnostic imaging/surgery ; }, abstract = {A 63-year-old man diagnosed with mixed-type cervical spondylotic amyotrophy exhibited severe atrophy in the right biceps brachii, teres major, and intrinsic hand muscles, resulting in level 3 muscle weakness. Magnetic resonance imaging showed symmetrical high signal, also referred to as the snake eye sign. Previously, he was erroneously diagnosed with amyotrophic lateral sclerosis. He had undergone anterior cervical surgery 7 years prior. At present, his right upper limb muscles display minimal atrophy compared with the left, with muscle strength nearing level 4, which is considered normal. We believe that prompt surgical intervention on diagnosis of cervical spondylotic amyotrophy, along with comprehensive postsurgery rehabilitation, can halt further deterioration of the condition and accelerate recovery.}, } @article {pmid37683611, year = {2023}, author = {Harding, O and Holzer, E and Riley, JF and Martens, S and Holzbaur, ELF}, title = {Damaged mitochondria recruit the effector NEMO to activate NF-κB signaling.}, journal = {Molecular cell}, volume = {83}, number = {17}, pages = {3188-3204.e7}, pmid = {37683611}, issn = {1097-4164}, support = {R01 NS060698/NS/NINDS NIH HHS/United States ; R37 NS060698/NS/NINDS NIH HHS/United States ; W 1261/FWF_/Austrian Science Fund FWF/Austria ; }, mesh = {*NF-kappa B/genetics ; *Signal Transduction ; I-kappa B Kinase/genetics ; Protein Serine-Threonine Kinases/genetics ; Mitochondria/genetics ; }, abstract = {Failure to clear damaged mitochondria via mitophagy disrupts physiological function and may initiate damage signaling via inflammatory cascades, although how these pathways intersect remains unclear. We discovered that nuclear factor kappa B (NF-κB) essential regulator NF-κB effector molecule (NEMO) is recruited to damaged mitochondria in a Parkin-dependent manner in a time course similar to recruitment of the structurally related mitophagy adaptor, optineurin (OPTN). Upon recruitment, NEMO partitions into phase-separated condensates distinct from OPTN but colocalizing with p62/SQSTM1. NEMO recruitment, in turn, recruits the active catalytic inhibitor of kappa B kinase (IKK) component phospho-IKKβ, initiating NF-κB signaling and the upregulation of inflammatory cytokines. Consistent with a potential neuroinflammatory role, NEMO is recruited to mitochondria in primary astrocytes upon oxidative stress. These findings suggest that damaged, ubiquitinated mitochondria serve as an intracellular platform to initiate innate immune signaling, promoting the formation of activated IKK complexes sufficient to activate NF-κB signaling. We propose that mitophagy and NF-κB signaling are initiated as parallel pathways in response to mitochondrial stress.}, } @article {pmid37682899, year = {2023}, author = {van Eenennaam, RM and Rave, N and Kruithof, WJ and Kruitwagen-van Reenen, ET and van den Berg, LH and Visser-Meily, JA and Beelen, A}, title = {Control in the absence of choice: A qualitative study on decision-making about gastrostomy in people with amyotrophic lateral sclerosis, caregivers, and healthcare professionals.}, journal = {PloS one}, volume = {18}, number = {9}, pages = {e0290508}, pmid = {37682899}, issn = {1932-6203}, mesh = {Humans ; *Caregivers ; Gastrostomy ; *Amyotrophic Lateral Sclerosis/therapy ; Health Personnel ; Delivery of Health Care ; }, abstract = {BACKGROUND: Gastrostomy is recommended in amyotrophic lateral sclerosis for long-term nutritional support, however, people with amyotrophic lateral sclerosis and healthcare professionals perceive decision-making as complex.

METHOD: To explore their perspectives on decision-making regarding gastrostomy, we used semi-structured interviews with people with amyotrophic lateral sclerosis, who had made a decision, and their caregivers; healthcare professionals were interviewed separately. Interviews were transcribed and analyzed thematically.

RESULTS: In 14 cases, 13 people with amyotrophic lateral sclerosis and 12 caregivers were interviewed; and in 10 of these cases, 5 healthcare professionals. Participants described decision-making on gastrostomy as a continuous process of weighing (future) clinical need against their values and beliefs in coming to a decision to accept or reject gastrostomy, or to postpone decision-making, while being supported by loved ones and healthcare professionals. Participants described gastrostomy as inevitable, but retained agency through control over the timing of decision-making. They said physical necessity, experiences of loss and identity, and expectations about gastrostomy placement were important factors in decision-making. Decision-making was described as a family affair, with caregivers supporting patient choice. healthcare professionals supported people with amyotrophic lateral sclerosis during the decision-making process and respected their autonomy and values. People with amyotrophic lateral sclerosis stressed the importance of adequate information on the procedure and the benefits.

CONCLUSION: People with amyotrophic lateral sclerosis feel in control of decision-making on gastrostomy if they are able to make their own choice at their own pace, supported by loved ones and healthcare professionals. Person-centered decision-making on gastrostomy requires early information exchange and repeated discussions with people with amyotrophic lateral sclerosis and their caregivers, incorporating their values and respecting patient choice.}, } @article {pmid37682317, year = {2023}, author = {Sassi, S and Bianchi, E and Diamanti, L and Tornabene, D and Sette, E and Medici, D and Matà, S and Leccese, D and Sperti, M and Martinelli, I and Ghezzi, A and Mandrioli, J and Iuzzolino, VV and Dubbioso, R and Trojsi, F and Passaniti, C and D'Alvano, G and Filosto, M and Padovani, A and Mazzini, L and De Marchi, F and Zinno, L and Nuredini, A and Bongioanni, P and Dolciotti, C and Canali, E and Toschi, G and Petrucci, A and Perna, A and Riso, V and Inghilleri, M and Libonati, L and Cambieri, C and Pupillo, E}, title = {Correction to: Retrospective observational study on the use of acetyl-L-carnitine in ALS.}, journal = {Journal of neurology}, volume = {270}, number = {11}, pages = {5358-5359}, doi = {10.1007/s00415-023-11960-3}, pmid = {37682317}, issn = {1432-1459}, } @article {pmid37682161, year = {2023}, author = {Tang, X and Zhan, Y and Yang, B and Du, B and Huang, J}, title = {Exploring the mechanism of Semen Strychni in treating amyotrophic lateral sclerosis based on network pharmacology.}, journal = {Medicine}, volume = {102}, number = {36}, pages = {e35101}, pmid = {37682161}, issn = {1536-5964}, mesh = {Humans ; *Semen ; *Amyotrophic Lateral Sclerosis/drug therapy ; Network Pharmacology ; Molecular Docking Simulation ; Phosphatidylinositol 3-Kinases ; }, abstract = {Semen Strychni (SS), known as an agonist of central nervous system, is a traditional herb widely used in treating amyotrophic lateral sclerosis (ALS) in small doses to relieve muscle weakness and improve muscle strength. However, the potential mechanisms and the main components of SS in treating ALS remain unclear. To explore the underlying mechanism of SS in treating ALS based on network pharmacology and molecular docking. The active components of SS were obtained using TCMSP, Herb, ETCM, and BATMAN-TCM. The targets of SS were gained from PharmMapper. The targets of ALS were searched on Genecards, Drugbank, DisGeNET, OMIM, TTD and GEO database. After obtaining the coincidence targets, we submitted them to the STRING database to build a protein-protein interaction network. Gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis were performed subsequently. The active components and targets were further investigated using molecular docking technology. 395 targets of SS and 1925 targets of ALS were obtained with 125 common targets. The protein-protein interaction analysis indicated that SRC, AKT1, MAPK1, EGFR, and HSP90AA1 received the higher degree value and were considered the central genes. The Ras, PI3K-Akt, and MAPK signaling pathway could be involved in the treatment of ALS. Brucine-N-oxide obtained the lowest binding energy in molecular docking. This study explored the mechanism of SS in the treatment of ALS and provides a new perspective for future study. However, further experimental studies are needed to validate the therapeutic effect.}, } @article {pmid37681895, year = {2023}, author = {Dunn, E and Steinert, JR and Stone, A and Sahota, V and Williams, RSB and Snowden, S and Augustin, H}, title = {Medium-Chain Fatty Acids Rescue Motor Function and Neuromuscular Junction Degeneration in a Drosophila Model of Amyotrophic Lateral Sclerosis.}, journal = {Cells}, volume = {12}, number = {17}, pages = {}, pmid = {37681895}, issn = {2073-4409}, support = {/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Animals ; *Amyotrophic Lateral Sclerosis/genetics ; Drosophila ; *Frontotemporal Dementia ; Drosophila melanogaster ; *Neurodegenerative Diseases ; Fatty Acids ; Neuromuscular Junction ; Larva ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disease characterised by progressive degeneration of the motor neurones. An expanded GGGGCC (G4C2) hexanucleotide repeat in C9orf72 is the most common genetic cause of ALS and frontotemporal dementia (FTD); therefore, the resulting disease is known as C9ALS/FTD. Here, we employ a Drosophila melanogaster model of C9ALS/FTD (C9 model) to investigate a role for specific medium-chain fatty acids (MCFAs) in reversing pathogenic outcomes. Drosophila larvae overexpressing the ALS-associated dipeptide repeats (DPRs) in the nervous system exhibit reduced motor function and neuromuscular junction (NMJ) defects. We show that two MCFAs, nonanoic acid (NA) and 4-methyloctanoic acid (4-MOA), can ameliorate impaired motor function in C9 larvae and improve NMJ degeneration, although their mechanisms of action are not identical. NA modified postsynaptic glutamate receptor density, whereas 4-MOA restored defects in the presynaptic vesicular release. We also demonstrate the effects of NA and 4-MOA on metabolism in C9 larvae and implicate various metabolic pathways as dysregulated in our ALS model. Our findings pave the way to identifying novel therapeutic targets and potential treatments for ALS.}, } @article {pmid37681887, year = {2023}, author = {Vasconcelos, CFM and Ribas, VT and Petrs-Silva, H}, title = {Shared Molecular Pathways in Glaucoma and Other Neurodegenerative Diseases: Insights from RNA-Seq Analysis and miRNA Regulation for Promising Therapeutic Avenues.}, journal = {Cells}, volume = {12}, number = {17}, pages = {}, pmid = {37681887}, issn = {2073-4409}, mesh = {Humans ; *Neurodegenerative Diseases/genetics/therapy ; RNA-Seq ; Homeostasis ; *Glaucoma/genetics/therapy ; *MicroRNAs/genetics ; }, abstract = {Advances in RNA-sequencing technologies have led to the identification of molecular biomarkers for several diseases, including neurodegenerative diseases, such as Alzheimer's, Parkinson's, Huntington's diseases and Amyotrophic Lateral Sclerosis. Despite the nature of glaucoma as a neurodegenerative disorder with several similarities with the other above-mentioned diseases, transcriptional data about this disease are still scarce. microRNAs are small molecules (~17-25 nucleotides) that have been found to be specifically expressed in the CNS as major components of the system regulating the development signatures of neurodegenerative diseases and the homeostasis of the brain. In this review, we sought to identify similarities between the functional mechanisms and the activated pathways of the most common neurodegenerative diseases, as well as to discuss how those mechanisms are regulated by miRNAs, using RNA-Seq as an approach to compare them. We also discuss therapeutically suitable applications for these disease hallmarks in clinical future studies.}, } @article {pmid37680659, year = {2023}, author = {Choayb, S and Harras, YE and Fikri, M and Kettani, NEE and Jiddane, M and Touarsa, F}, title = {Brain MRI abnormalities associated with amyotrophic lateral sclerosis: A case illustration.}, journal = {Radiology case reports}, volume = {18}, number = {11}, pages = {3972-3974}, pmid = {37680659}, issn = {1930-0433}, abstract = {Amyotrophic lateral sclerosis is a progressive neurodegenerative pathology. It involves both upper and lower motor neurons, leading to their degeneration. Lower motor neurons can be detected with an electromyogram, but the detection of upper motor neuron dysfunction may be more accurate using MRI. We present the case of a 64-year-old woman with amyotrophic lateral sclerosis, presenting the motor band sign and the bright tongue sign on MRI.}, } @article {pmid37680538, year = {2023}, author = {Dunn, E and Zhang, B and Sahota, VK and Augustin, H}, title = {Potential benefits of medium chain fatty acids in aging and neurodegenerative disease.}, journal = {Frontiers in aging neuroscience}, volume = {15}, number = {}, pages = {1230467}, pmid = {37680538}, issn = {1663-4365}, abstract = {Neurodegenerative diseases are a large class of neurological disorders characterized by progressive dysfunction and death of neurones. Examples include Alzheimer's disease, Parkinson's disease, frontotemporal dementia, and amyotrophic lateral sclerosis. Aging is the primary risk factor for neurodegeneration; individuals over 65 are more likely to suffer from a neurodegenerative disease, with prevalence increasing with age. As the population ages, the social and economic burden caused by these diseases will increase. Therefore, new therapies that address both aging and neurodegeneration are imperative. Ketogenic diets (KDs) are low carbohydrate, high-fat diets developed initially as an alternative treatment for epilepsy. The classic ketogenic diet provides energy via long-chain fatty acids (LCFAs); naturally occurring medium chain fatty acids (MCFAs), on the other hand, are the main components of the medium-chain triglyceride (MCT) ketogenic diet. MCT-based diets are more efficient at generating the ketone bodies that are used as a secondary energy source for neurones and astrocytes. However, ketone levels alone do not closely correlate with improved clinical symptoms. Recent findings suggest an alternative mode of action for the MCFAs, e.g., via improving mitochondrial biogenesis and glutamate receptor inhibition. MCFAs have been linked to the treatment of both aging and neurodegenerative disease via their effects on metabolism. Through action on multiple disease-related pathways, MCFAs are emerging as compounds with notable potential to promote healthy aging and ameliorate neurodegeneration. MCFAs have been shown to stimulate autophagy and restore mitochondrial function, which are found to be disrupted in aging and neurodegeneration. This review aims to provide insight into the metabolic benefits of MCFAs in neurodegenerative disease and healthy aging. We will discuss the use of MCFAs to combat dysregulation of autophagy and mitochondrial function in the context of "normal" aging, Parkinson's disease, amyotrophic lateral sclerosis and Alzheimer's disease.}, } @article {pmid37679883, year = {2024}, author = {de Boer, EMJ and Demaegd, KC and de Bie, CI and Veldink, JH and van den Berg, LH and van Es, MA}, title = {Familial motor neuron disease: co-occurrence of PLS and ALS (-FTD).}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {25}, number = {1-2}, pages = {53-60}, doi = {10.1080/21678421.2023.2255621}, pmid = {37679883}, issn = {2167-9223}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/epidemiology/genetics ; *Frontotemporal Dementia/genetics ; Prospective Studies ; *Motor Neuron Disease/epidemiology/genetics/pathology ; *Muscular Atrophy, Spinal/epidemiology/genetics ; }, abstract = {OBJECTIVE: To report the frequency and characteristics of patients diagnosed with primary lateral sclerosis (PLS) with a positive family history for motor neuron diseases (MND) in the Netherlands and to compare our findings to the literature.

METHODS: Patients were identified through our ongoing, prospective population-based study on MND in The Netherlands, which also includes a standardized collection of patient characteristics, genetic testing, and family history. Only patients meeting the latest consensus criteria for definite PLS were included. The family history was considered positive for MND if any family members had been diagnosed with PLS, amyotrophic lateral sclerosis (ALS)(-FTD), or progressive muscular atrophy (PMA). Additionally, the literature was reviewed on PLS cases in which MND co-occurred within the same family.

RESULTS: We identified 392 definite PLS cases, resulting in 9 families with a PLS patient and a positive family history for MND (2.3%). In only one of these pedigrees, a pathogenic variant (C9orf72 repeat expansion) was found. Our literature review revealed 23 families with a co-occurrence of PLS and MND, with 12 of them having a potentially pathogenic genetic variant.

CONCLUSIONS: The consistent observation of PLS patients with a positive family history for MND, evident in both our study and the literature, implies the presence of shared underlying genetic factors between PLS and ALS. However, these factors are yet to be elucidated.}, } @article {pmid37679868, year = {2024}, author = {Martinelli, I and Zucchi, E and Simonini, C and Gianferrari, G and Bedin, R and Biral, C and Ghezzi, A and Fini, N and Carra, S and Mandrioli, J}, title = {SerpinA1 levels in amyotrophic lateral sclerosis patients: An exploratory study.}, journal = {European journal of neurology}, volume = {31}, number = {1}, pages = {e16054}, pmid = {37679868}, issn = {1468-1331}, support = {bando per la ricerca clinica 2015//Agenzia di Ricerca per la Sclerosi Laterale Amiotrofica/ ; grant number 2016-02364678//Agenzia Italiana del Farmaco, Ministero della Salute/ ; Neurobiobanca di Modena//Fondazione Cassa di Risparmio di Modena/ ; bando per la ricerca finalizzata 2016, grant number RF-2016-02361616//Ministero della Salute/ ; bando FAR 2021, Progetti di ricerca Interdisciplinari Mission Oriented, NEURALS project//Università Degli Studi di Modena e Reggio Emila/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis ; Disease Progression ; Neurofilament Proteins/cerebrospinal fluid ; Prognosis ; Biomarkers ; }, abstract = {BACKGROUND: SerpinA1, a serine protease inhibitor, is involved in the modulation of microglial-mediated inflammation in neurodegenerative diseases. We explored SerpinA1 levels in cerebrospinal fluid (CSF) and serum of amyotrophic lateral sclerosis (ALS) patients to understand its potential role in the pathogenesis of the disease.

METHODS: SerpinA1, neurofilament light (NfL) and heavy (NfH) chain, and chitinase-3-like protein-1 (CHI3L1) were determined in CSF and serum of ALS patients (n = 110) and healthy controls (n = 10) (automated next-generation ELISA), and correlated with clinical parameters, after identifying three classes of progressors (fast, intermediate, slow). Biomarker levels were analyzed for diagnostic power and association with progression and survival.

RESULTS: SerpinA1serum was significantly decreased in ALS (median: 1032 μg/mL) compared with controls (1343 μg/mL) (p = 0.02). SerpinA1CSF was elevated only in fast progressors (8.6 μg/mL) compared with slow (4.43 μg/mL, p = 0.01) and intermediate (4.42 μg/mL, p = 0.03) progressors. Moreover, SerpinA1CSF correlated with neurofilament and CHI3L1 levels in CSF. Contrarily to SerpinA1CSF , neurofilament and CHI3L1 concentrations in CSF correlated with measures of disease progression in ALS, while SerpinA1serum mildly related with time to generalization (rho = 0.20, p = 0.04). In multivariate analysis, the ratio between serum and CSF SerpinA1 (SerpinA1 ratio) and NfHCSF were independently associated with survival.

CONCLUSIONS: Higher SerpinA1CSF levels are found in fast progressors, suggesting SerpinA1 is a component of the neuroinflammatory mechanisms acting upon fast-progressing forms of ALS. Both neurofilaments or CHI3L1CSF levels outperformed SerpinA1 at predicting disease progression rate in our cohort, and so the prognostic value of SerpinA1 alone as a measure remains inconclusive.}, } @article {pmid37678221, year = {2024}, author = {Huynh, A and Adams, K and Barnett-Tapia, C and Kalra, S and Zinman, L and Yunusova, Y}, title = {Accessing and Receiving Speech-Language Pathology Services at the Multidisciplinary Amyotrophic Lateral Sclerosis Clinic: An Exploratory Qualitative Study of Patient Experiences and Needs.}, journal = {Journal of speech, language, and hearing research : JSLHR}, volume = {67}, number = {10S}, pages = {4025-4037}, pmid = {37678221}, issn = {1558-9102}, support = {R01 DC017291/DC/NIDCD NIH HHS/United States ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/psychology/therapy/complications ; *Speech-Language Pathology ; Male ; Female ; *Qualitative Research ; Middle Aged ; Aged ; *Caregivers/psychology ; *Health Services Accessibility ; Canada ; Health Services Needs and Demand ; Adult ; }, abstract = {PURPOSE: This study sought to explore how patients with amyotrophic lateral sclerosis (ALS) presenting with coexisting bulbar and cognitive impairments and their caregivers experienced the speech-language pathologist (SLP) services provided in multidisciplinary ALS clinics in Canada and identified their perceived needs for bulbar symptom management.

METHOD: This qualitative study was informed by interpretive description. Seven interviews were conducted with patients with severe bulbar dysfunction or severe bulbar and cognitive dysfunction due to ALS or ALS-frontotemporal dementia, respectively, and/or their caregivers. Purposive sampling was used to recruit individuals with severe bulbar or bulbar and cognitive disease. Thematic analysis was used to analyze interview data.

RESULTS: Patients and caregivers reported difficulties with accessing and receiving SLP services at the multidisciplinary ALS clinic. These difficulties were further exacerbated in those with severe cognitive disease. Participants expressed a need for more specific (i.e., disease and service-related) information and personalized care to address their changing needs and preferences. Engaging caregivers earlier in SLP appointments was perceived as vital to support care planning and provide in-time caregiver education.

CONCLUSIONS: This study highlighted the challenges experienced by patients and caregivers in accessing and receiving SLP services. There is a pressing need for a more person-centered approach to ALS care and a continuing need for education of SLPs on care provision in cases of complex multisymptom diseases within a multidisciplinary ALS clinic.

SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.24069222.}, } @article {pmid37675986, year = {2023}, author = {Sonobe, Y and Lee, S and Krishnan, G and Gu, Y and Kwon, DY and Gao, FB and Roos, RP and Kratsios, P}, title = {Translation of dipeptide repeat proteins in C9ORF72 ALS/FTD through unique and redundant AUG initiation codons.}, journal = {eLife}, volume = {12}, number = {}, pages = {}, pmid = {37675986}, issn = {2050-084X}, support = {R01 NS101986/NS/NINDS NIH HHS/United States ; R37 NS057553/NS/NINDS NIH HHS/United States ; RF1 NS101986/NS/NINDS NIH HHS/United States ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/pathology ; *C9orf72 Protein/genetics/metabolism ; Codon, Initiator/genetics ; Dipeptides/genetics/metabolism ; *Frontotemporal Dementia/pathology ; *Pick Disease of the Brain ; Proteins/genetics ; }, abstract = {A hexanucleotide repeat expansion in C9ORF72 is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). A hallmark of ALS/FTD pathology is the presence of dipeptide repeat (DPR) proteins, produced from both sense GGGGCC (poly-GA, poly-GP, poly-GR) and antisense CCCCGG (poly-PR, poly-PG, poly-PA) transcripts. Translation of sense DPRs, such as poly-GA and poly-GR, depends on non-canonical (non-AUG) initiation codons. Here, we provide evidence for canonical AUG-dependent translation of two antisense DPRs, poly-PR and poly-PG. A single AUG is required for synthesis of poly-PR, one of the most toxic DPRs. Unexpectedly, we found redundancy between three AUG codons necessary for poly-PG translation. Further, the eukaryotic translation initiation factor 2D (EIF2D), which was previously implicated in sense DPR synthesis, is not required for AUG-dependent poly-PR or poly-PG translation, suggesting that distinct translation initiation factors control DPR synthesis from sense and antisense transcripts. Our findings on DPR synthesis from the C9ORF72 locus may be broadly applicable to many other nucleotide repeat expansion disorders.}, } @article {pmid37674720, year = {2023}, author = {Chen, S and Puri, A and Bell, B and Fritsche, J and Palacios, H and Balch, M and Sprunger, M and Howard, M and Patterson, J and Patti, G and Davis, A and Jackrel, M}, title = {HtrA1 prevents and reverses α-synuclein aggregation, rendering it non-toxic and seeding incompetent.}, journal = {Research square}, volume = {}, number = {}, pages = {}, pmid = {37674720}, issn = {2693-5015}, support = {K08 NS101118/NS/NINDS NIH HHS/United States ; R35 GM128772/GM/NIGMS NIH HHS/United States ; }, abstract = {Parkinson disease (PD) is closely linked to the misfolding and accumulation of α-synuclein (α-syn) into Lewy bodies. HtrA1 is a PDZ serine protease that degrades fibrillar tau, which is associated with Alzheimer disease (AD). Further, inactivating mutations to mitochondrial HtrA2 have been implicated in PD. Here, we establish that HtrA1 inhibits the aggregation of α-syn as well as FUS and TDP-43, which are implicated in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). We demonstrate that the protease domain of HtrA1 is necessary and sufficient for inhibition of aggregation, yet this activity is independent of HtrA1 proteolytic activity. Further, we find that HtrA1 also disaggregates preformed α-syn fibrils, which may promote their clearance. Treatment of α-syn fibrils with HtrA1 renders α-syn incapable of seeding the aggregation of endogenous α-syn in mammalian biosensor cells. We find that HtrA1 remodels α-syn by specifically targeting the NAC domain, which is the key domain that catalyzes α-syn oligomerization and fibrillization. Finally, in a primary neuron model of α-syn aggregation, we show that HtrA1 and its proteolytically inactive form both detoxify α-syn and prevent the formation of hyperphosphorylated α-syn accumulations. Our findings suggest that HtrA1 prevents aggregation and promotes disaggregation of multiple disease-associated proteins, and may be a therapeutic target for treating a range of neurodegenerative disorders.}, } @article {pmid37674380, year = {2024}, author = {Volpato, E and Banfi, P and Poletti, V and Pagnini, F}, title = {Living beyond loss: a qualitative investigation of caregivers' experiences after the death of their relatives with amyotrophic lateral sclerosis.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {25}, number = {1-2}, pages = {75-87}, doi = {10.1080/21678421.2023.2255628}, pmid = {37674380}, issn = {2167-9223}, mesh = {Humans ; Male ; Female ; Middle Aged ; *Amyotrophic Lateral Sclerosis/psychology ; Caregivers/psychology ; Social Support ; Coping Skills ; Qualitative Research ; }, abstract = {BACKGROUND: Caregivers of Amyotrophic Lateral Sclerosis (ALS) patients experience varying psychological responses following the patient's death, including sadness, loneliness, guilt, and a loss of purpose.

OBJECTIVES: This research aims to investigate the caregiver journey experienced from the time of diagnosis to the loss of a care recipient, with a specific focus on understanding the factors that contribute to improved coping with bereavement.

METHODS: The present study used the Interpretative Phenomenological Approach (IPA) to qualitatively explore the accounts of 41 Italian bereaved caregivers of people affected by ALS (Mean Age = 59.78; Female: 60.98%; Male: 39.02%).

RESULTS: Results revealed 5 overarching themes representing 5 macro areas that emerged from the analysis of the interviews ("Caregiver's perception of his/her life", "Caregiver's feelings", "Caregiver's life after patient's death", "Caregiver's disease description", "Caregiver's help resources"), these were further defined based on 12 main themes, which were, in turn, articulated into 30 subthemes. The transition from life before ALS ("a peaceful landscape") to caregiver life (compared to the color "black") was a "shock", during which caregivers had to change their needs. However, life after the person living with ALS' death was both characterized by a sense of "re-birth" and "emptiness", and a general need for "psychological assistance" and "social support".

CONCLUSIONS: Results emphasize the need to improve the psychological support offered to caregivers of person living with ALS after the patient's death, tailoring it to the specificity of the condition, to meet their emotional needs, reduce isolation and help them cope with practical challenges and plans.}, } @article {pmid37674309, year = {2024}, author = {Yamamoto, M and Tsukasaki, K and Kyota, K}, title = {Relationship Between Resilience Factors and Caregiving Status of Families of Patients with Amyotrophic Lateral Sclerosis (ALS) in Japan.}, journal = {Journal of community health nursing}, volume = {41}, number = {1}, pages = {44-56}, doi = {10.1080/07370016.2023.2254771}, pmid = {37674309}, issn = {1532-7655}, mesh = {Humans ; Male ; Female ; *Amyotrophic Lateral Sclerosis/therapy ; Adaptation, Psychological ; *Resilience, Psychological ; Cross-Sectional Studies ; Japan ; Quality of Life ; Caregivers ; }, abstract = {PURPOSE: To identify innate and acquired factors leading to amyotrophic lateral sclerosis (ALS) caregivers' resilience, the relationships among these factors, and caregiving situations.

DESIGN: Cross-sectional study.

METHODS: Questionnaires measuring resilience, caregiver burden, and family functioning were mailed to caregivers of ALS patients in Japan.

FINDINGS: The 370 responses showed that increases in both innate and acquired factors were related to having an ALS association membership, while decreases were associated with reduced family function. Increases in innate factors were related to employment and those consenting to ventilators, while decreases were associated with being male and having a sense of the care burden. Decreases in acquired factors were related to the presence of an alternative caregiver.

CONCLUSIONS: By identifying the caregiving situation based on innate and acquired factors, we were able to identify the significance and direction of specific caregiving support.

CLINICAL EVIDENCE: Community health nurses should focus on improving family function and creating a supportive environment. Further, support for male and non-working caregivers should be strengthened and consultation on the use of respiratory equipment promoted to reduce the caregiving burden.}, } @article {pmid37672915, year = {2023}, author = {Rajagopalan, V and Pioro, EP}, title = {Graph network measures reveal distinct white matter abnormalities in motor and extra-motor brain regions of two UMN-predominant ALS subtypes.}, journal = {Journal of the neurological sciences}, volume = {452}, number = {}, pages = {120765}, doi = {10.1016/j.jns.2023.120765}, pmid = {37672915}, issn = {1878-5883}, mesh = {Humans ; *White Matter/diagnostic imaging ; *Amyotrophic Lateral Sclerosis/diagnostic imaging ; Cerebellum ; Echo-Planar Imaging ; *Leukoaraiosis ; Motor Neurons ; }, abstract = {BACKGROUND: Routine clinical magnetic resonance imaging (MRI) shows bilateral corticospinal tract (CST) hyperintensity in some patients with upper motor neuron (UMN)-predominant ALS (ALS-CST+) but not in others (ALS-CST-). Although, similar in their UMN features, the ALS-CST+ patient group is significantly younger in age, has faster disease progression and shorter survival than the ALS-CST- patient group. Reasons for the differences are unclear.

METHOD: In order to evaluate more objective MRI measures of these ALS subgroups, we used diffusion tensor images (DTI) obtained using single shot echo planar imaging sequence from 1.5 T Siemens MRI Scanner. We performed an exploratory whole brain white matter (WM) network analysis using graph theory approach on 45 ALS patients (ALS-CST+) (n = 21), and (ALS-CST-) (n = 24) and neurological controls (n = 14).

RESULTS: Significant (p < 0.05) differences in nodal degree measure between ALS patients and controls were observed in motor and extra motor regions, supplementary motor area, subcortical WM regions, cerebellum and vermis. Importantly, WM network abnormalities were significantly (p < 0.05) different between ALS-CST+ and ALS-CST- subgroups. Compared to neurologic controls, both ALS subgroups showed hubs in the right superior occipital gyrus and cuneus as well as significantly (p < 0.05) reduced small worldness supportive of WM network damage.

CONCLUSIONS: Significant differences between ALS-CST+ and ALS-CST- subgroups of WM network abnormalities, age of onset, symptom duration prior to MRI, and progression rate suggest these patients represent distinct clinical phenotypes and possibly pathophysiologic mechanisms of ALS.}, } @article {pmid37672770, year = {2023}, author = {Naveed, M and Aqib Shabbir, M and Aziz, T and Hurraira, HM and Fatima Zaidi, S and Athar, R and Chattha, HA and Alharbi, M and Alshammari, A and Alasmari, AF}, title = {CRISPR-Cas9 guided rna based model for the treatment of Amyotrophic Lateral Sclerosis: A progressive neurodegenerative disorder.}, journal = {Acta biochimica Polonica}, volume = {70}, number = {3}, pages = {643-653}, doi = {10.18388/abp.2020_6789}, pmid = {37672770}, issn = {1734-154X}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/therapy ; CRISPR-Cas Systems/genetics ; Gene Editing ; Muscles ; RNA, Guide, CRISPR-Cas Systems ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder that leads to the degeneration of motor neurons and the weakening of muscles. Despite extensive research efforts, there is currently no cure for ALS and existing treatments only address its symptoms. To address this unmet medical need, genome editing technologies, such as CRISPR-Cas9, have emerged as a promising solution for the development of new treatments for ALS. Studies have shown that CRISPR-Cas9-guided RNAs have the potential to provide accurate and effective silencing in the genetic disease of ALS. Results have demonstrated a 67% on-target score and a 98% off-target score with GC content within the range of 40-60%. This is further validated by the correlation between the gRNA's structural accuracy and the minimum free energy. The use of CRISPR-Cas9 provides a unique opportunity to target this disease at the molecular level, offering hope for the development of a more effective treatment. In silico and computational therapeutic approaches for ALS suggest that the CRISPR-Cas9 protein holds promise as a future treatment candidate. The CRISPR mechanism and the specificity of gRNA provide a novel therapeutic approach for this genetic disease, offering new hope to those affected by ALS. This study highlights the potential of CRISPR-Cas9 as a promising solution for the development of new treatments for ALS. Further research is required to validate these findings in preclinical and clinical trials and to establish the safety and efficacy of this approach in the treatment of ALS.}, } @article {pmid37671427, year = {2023}, author = {Gastelum, S and Michael, AF and Bolger, TA}, title = {Saccharomyces cerevisiae as a research tool for RNA-mediated human disease.}, journal = {Wiley interdisciplinary reviews. RNA}, volume = {}, number = {}, pages = {e1814}, doi = {10.1002/wrna.1814}, pmid = {37671427}, issn = {1757-7012}, support = {R01 GM136827/GM/NIGMS NIH HHS/United States ; GM136827/GM/NIGMS NIH HHS/United States ; }, abstract = {The budding yeast, Saccharomyces cerevisiae, has been used for decades as a powerful genetic tool to study a broad spectrum of biological topics. With its ease of use, economic utility, well-studied genome, and a highly conserved proteome across eukaryotes, it has become one of the most used model organisms. Due to these advantages, it has been used to study an array of complex human diseases. From broad, complex pathological conditions such as aging and neurodegenerative disease to newer uses such as SARS-CoV-2, yeast continues to offer new insights into how cellular processes are affected by disease and how affected pathways might be targeted in therapeutic settings. At the same time, the roles of RNA and RNA-based processes have become increasingly prominent in the pathology of many of these same human diseases, and yeast has been utilized to investigate these mechanisms, from aberrant RNA-binding proteins in amyotrophic lateral sclerosis to translation regulation in cancer. Here we review some of the important insights that yeast models have yielded into the molecular pathology of complex, RNA-based human diseases. This article is categorized under: RNA in Disease and Development > RNA in Disease.}, } @article {pmid37671079, year = {2023}, author = {Alothmani, OS and Siddiqui, AY}, title = {Accuracy of Root ZX Electronic Apex Locator in Relation to Two Different Employment Protocols: An In Vitro Study.}, journal = {Cureus}, volume = {15}, number = {9}, pages = {e44659}, pmid = {37671079}, issn = {2168-8184}, abstract = {Objective The aim of this study is to determine the apical level of the root canal, whether it is the apical foramen or a level coronal to it, that Root ZX (J. Morita Co., Kyoto, Japan) targets and to identify its employment protocol that provides better accuracy. Methods Actual lengths (ALs) of 75 extracted single-rooted teeth were obtained by inserting a K-file size 8 until its tip was in level with the most coronal border of the apical foramen. Reference length (RL) was calculated by deducting 0.5 mm from AL. Roots were placed in porous sponge block soaked with Ringer's solution, and canals were irrigated with 2 mL of 5% sodium hypochlorite. The blinded operator used Root ZX to measure lengths with K-file size 8. In the first tested employment protocol, the file was advanced to the "APEX mark" of the digital display, and the length was obtained. The second employment protocol followed the manufacturer's recommendations by inserting the file until the "APEX mark" followed by its withdrawal to the "0.5 mark." Stability of the digital meter for 5 seconds was mandatory before recording the lengths. All measurements were repeated one week later and then both measurements were averaged to represent "APEX mark" and "0.5 mark," respectively. Data were analyzed using t-test, with significance set at 0.05. Results Regardless of the employment protocol, most registered lengths were longer than targeted. The mean "APEX mark" was significantly longer than the mean AL (P=0.000), and the mean "0.5 mark" was significantly longer than the mean RL (P=0.000). Although the mean "0.5 mark" was longer than the mean AL, the difference was not significant (P=0.07). Conclusion The apical level of the root canal targeted by the Root ZX was the apical foramen. The most accurate employment protocol to achieve that is to use the Root ZX according to the manufacturer's recommendations.}, } @article {pmid37671010, year = {2023}, author = {Broadhead, MJ and Ayvazian-Hancock, A and Doucet, K and Kantelberg, O and Motherwell, L and Zhu, F and Grant, SGN and Horrocks, MH and Miles, GB}, title = {Synaptic expression of TAR-DNA-binding protein 43 in the mouse spinal cord determined using super-resolution microscopy.}, journal = {Frontiers in molecular neuroscience}, volume = {16}, number = {}, pages = {1027898}, pmid = {37671010}, issn = {1662-5099}, support = {MILES/APR18/863-791/MNDA_/Motor Neurone Disease Association/United Kingdom ; }, abstract = {Amyotrophic Lateral Sclerosis (ALS) is characterised by a loss of motor neurons in the brain and spinal cord that is preceded by early-stage changes in synapses that may be associated with TAR-DNA-Binding Protein 43 (TDP-43) pathology. Cellular inclusions of hyperphosphorylated TDP-43 (pTDP-43) are a key hallmark of neurodegenerative diseases such ALS. However, there has been little characterisation of the synaptic expression of TDP-43 inside subpopulations of spinal cord synapses. This study utilises a range of high-resolution and super-resolution microscopy techniques with immunolabelling, as well as an aptamer-based TDP-43 labelling strategy visualised with single-molecule localisation microscopy, to characterise and quantify the presence of pTDP-43 in populations of excitatory synapses near where motor neurons reside in the lateral ventral horn of the mouse lumbar spinal cord. We observe that TDP-43 is expressed in approximately half of spinal cord synapses as nanoscale clusters. Synaptic TDP-43 clusters are found most abundantly at synapses associated with VGLUT1-positive presynaptic terminals, compared to VGLUT2-associated synapses. Our nanoscopy techniques showed no difference in the subsynaptic expression of pTDP-43 in the ALS mouse model, SOD1[G93a], compared to healthy controls, despite prominent structural deficits in VGLUT1-associated synapses in SOD1[G93a] mice. This research characterises the basic synaptic expression of TDP-43 with nanoscale precision and provides a framework with which to investigate the potential relationship between TDP-43 pathology and synaptic pathology in neurodegenerative diseases.}, } @article {pmid37670160, year = {2023}, author = {Devalckeneer, A and Bourgeois, P and Caudron, Y and Estrade, L and Obled, L and Leclerc, X and Assaker, R and Lejeune, JP and Aboukais, R}, title = {Surgical evolution in spinal dural arteriovenous fistula treatment-a 7 years monocentric experience.}, journal = {Neurosurgical review}, volume = {46}, number = {1}, pages = {225}, pmid = {37670160}, issn = {1437-2320}, mesh = {Adult ; Humans ; *Central Nervous System Vascular Malformations ; Cerebrospinal Fluid Leak ; Laminectomy ; Retrospective Studies ; *Spinal Cord Diseases ; }, abstract = {Accounting for 70% of all spinal vascular malformations, spinal dural arteriovenous fistulas (SDAVF) are the most common type of malformation. Interruption of the fistulous arterialized vein point is the goal of surgical treatment. The aim of the study was to compare open surgery (laminectomy) versus minimal invasive surgery (MIS) in SDAVF treatment. Between March 2013 and March 2020, we retrospectively collected 21 consecutive adult patients with SDAVF. Since March 2017, MIS has been routinely used for surgical treatment. Pre- and post-operative clinical evaluations used Aminoff-Logue score (ALS). Complication rate was noted. Post-operative occlusion of the malformation was confirmed by digital subtraction angiography (DSA) in all patients. MIS was compared to open surgery in terms of efficacy and complications with statistical evaluation. Standard laminectomy was performed in 12 patients and MIS technique in 9 patients. No difference was noted on pre-operative parameters. ALS and MRI signs of myelopathy were improved in all cases except for 1 patient in each group. All SDAVFs were excluded based on post-operative DSA. Significant differences were noted between the 2 groups in terms of perioperative blood loss (p<0.001), post-operative pain visual analog scale values (p<0.001), and first time out of bed (p<0.001). Wrong level surgery occurred in one patient in each group; patients were re-operated using the same technique. No infection or cerebrospinal fluid (CSF) leak was noted. In our experience, MIS is a safe alternative to open laminectomy for SDAVF treatment. MIS contributes to patient comfort and minimizes blood loss without increasing complication rate.}, } @article {pmid37670116, year = {2023}, author = {Kang, J and Lim, L and Song, J}, title = {ATP induces folding of ALS-causing C71G-hPFN1 and nascent hSOD1.}, journal = {Communications chemistry}, volume = {6}, number = {1}, pages = {186}, pmid = {37670116}, issn = {2399-3669}, abstract = {ALS-causing C71G-hPFN1 coexists in both folded and unfolded states, while nascent hSOD1 is unfolded. So far, the mechanisms underlying their ALS-triggering potential remain enigmatic. Here we show by NMR that ATP completely converts C71G-hPFN1 into the folded state at a 1:2 ratio, while inducing nascent hSOD1 into two co-existing states at a 1:8 ratio. Surprisingly, the inducing capacity of ATP comes from its triphosphate, but free triphosphate triggers aggregation. The inducing capacity ranks as: ATP = ATPP = PPP > ADP = AMP-PNP = AMP-PCP = PP, while AMP, adenosine, P, and NaCl show no conversion. Mechanistically, ATP and triphosphate appear to enhance the intrinsic folding capacity encoded in the sequences, as unveiled by comparing conformations and dynamics of ATP- and Zn[2+]-induced hSOD1 folded states. Our study provides a mechanism for the finding that some single-cell organisms employ polyphosphates as primordial chaperones, and sheds light on the enigma of age-related onset of familial ALS and risk increase of neurodegenerative diseases.}, } @article {pmid37669876, year = {2023}, author = {Quinn, L and Bird, P and Remsing, S and Reeves, K and Lilford, R}, title = {Unintended consequences of the 18-week referral to treatment standard in NHS England: a threshold analysis.}, journal = {BMJ quality & safety}, volume = {32}, number = {12}, pages = {712-720}, pmid = {37669876}, issn = {2044-5423}, mesh = {Humans ; *State Medicine ; *Hospitals ; Patients ; England ; Referral and Consultation ; }, abstract = {OBJECTIVE: In 2012, an '18-week referral to treatment standard' was introduced in England. Among people on the list of those waiting for hospital treatment at a point in time, the standard states that at least '92% of patients should have been waiting for less than 18 weeks'. Targets can have unintended consequences, where patients are prioritised based on the target rather than clinical need. Such an effect will be evident as a spike in the number of hospital trusts at the target threshold, referred to as a threshold effect. This study examines for threshold effects across all non-specialist acute NHS England hospital trusts by financial year.

METHODS: A retrospective observational study of publicly available data examined waiting times for patients on the waiting list. We examined trust performance against the 92% target by financial year, from 2015/16 to 2021/22, using Cattaneo et al's manipulation density test (test for discontinuity/spike in data around target threshold) for all patients and by type of treatment.

RESULTS: The proportion of NHS hospital trusts meeting the 92% target deteriorated over time. From 2015/16 to 2019/20, there was strong evidence of a threshold effect at the 92% target (p<0.001). There was no evidence of a threshold effect in 2020/21 (p=0.063) or 2021/22 (p=0.090). Threshold effects were present across most types of treatment in 2016/17 and fewer types from 2017/18 onwards.

CONCLUSION: We observed striking evidence of a threshold effect suggesting that while targets change behaviour, they do so in a selective way, focusing on the threshold rather than a pervasive improvement in practice. However, at the height of the pandemic, as almost no trusts could reach the target, the threshold effect disappeared.}, } @article {pmid37669872, year = {2023}, author = {}, title = {Dextromethorphan-Quinidine (Nuedexta) Improves Swallowing in Bulbar Onset ALS Patients With Pseudobulbar Affect - Pre-Post Observational Study in 86 ALS Patients (P4.4-019).}, journal = {Neurology}, volume = {101}, number = {16}, pages = {730}, doi = {10.1212/WNL.0000000000207886}, pmid = {37669872}, issn = {1526-632X}, } @article {pmid37668918, year = {2024}, author = {Asakawa, K and Handa, H and Kawakami, K}, title = {In Vivo Optogenetic Phase Transition of an Intrinsically Disordered Protein.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {2707}, number = {}, pages = {257-264}, pmid = {37668918}, issn = {1940-6029}, mesh = {Animals ; *Intrinsically Disordered Proteins/genetics ; Optogenetics ; Zebrafish ; DNA-Binding Proteins ; Motor Neurons ; }, abstract = {Proteins containing intrinsically disordered regions (IDRs) control a wide variety of cellular processes by assembly of membrane-less organelles via IDR-mediated liquid-liquid phase separation. Dysregulated IDR-mediated phase transition has been implicated in the pathogenesis of diseases characterized by deposition of abnormal protein aggregates. Here, we describe a method to enhance interactions between the IDRs of the RNA/DNA-binding protein and TAR DNA-binding protein 43 (TDP-43) by light to drive its phase transition in the motor neurons of zebrafish. The optically controlled TDP-43 phase transition in motor neurons, in vivo, provides a unique opportunity to evaluate the impact of dysregulated TDP-43 phase transition on the physiology of motor neurons. This will help to address the etiology of neurodegenerative diseases associated with abnormal TDP-43 phase transition and aggregation, including amyotrophic lateral sclerosis (ALS).}, } @article {pmid37668704, year = {2023}, author = {Martinelli, I and Ghezzi, A and Zucchi, E and Gianferrari, G and Ferri, L and Moglia, C and Manera, U and Solero, L and Vasta, R and Canosa, A and Grassano, M and Brunetti, M and Mazzini, L and De Marchi, F and Simonini, C and Fini, N and Vinceti, M and Pinti, M and Chiò, A and Calvo, A and Mandrioli, J}, title = {Predictors for progression in amyotrophic lateral sclerosis associated to SOD1 mutation: insight from two population-based registries.}, journal = {Journal of neurology}, volume = {270}, number = {12}, pages = {6081-6092}, pmid = {37668704}, issn = {1432-1459}, support = {RF-2016-02362405//Ministero della Salute/ ; 259867//Seventh Framework Programme/ ; 2017SNW5MB//Ministero dell'Istruzione, dell'Università e della Ricerca/ ; 101017598//Ministero dell'Istruzione, dell'Università e della Ricerca/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/epidemiology/genetics ; Superoxide Dismutase-1/genetics ; Mutation ; Registries ; *Neoplasms ; Superoxide Dismutase/genetics ; }, abstract = {BACKGROUND: Uncovering distinct features and trajectories of amyotrophic lateral sclerosis (ALS) associated with SOD1 mutations (SOD1-ALS) can provide valuable insights for patient' counseling and stratification for trials, and interventions timing. Our study aims to pinpoint distinct clinical characteristics of SOD1-ALS by delving into genotype-phenotype correlations and factors that potentially impact disease progression.

METHODS: This is a retrospective observational study of a SOD1-ALS cohort from two Italian registers situated in the regions of Emilia-Romagna, Piedmont and Valle d'Aosta.

RESULTS: Out of 2204 genotyped ALS patients, 2.5% carried SOD1 mutations, with a M:F ratio of 0.83. SOD1-ALS patients were younger, and more frequently reported a family history of ALS and/or FTD. SOD1-ALS had a longer survival compared to patients without ALS-associated gene mutations. However, here was considerable variability in survival across distinct SOD1 mutations, with an average survival of less than a year for the L39V, G42S, G73S, D91N mutations. Among SOD1-ALS, multivariate analysis showed that, alongside established clinical prognostic factors such as advanced age at onset and high progression rate at diagnosis, mutations located in exon 2 or within highly conserved gene positions predicted worse survival. Conversely, among comorbidities, cancer history was independently associated with longer survival.

INTERPRETATION: Within the context of an overall slower disease, SOD1-ALS exhibits some degree of heterogeneity linked to the considerable genetic diversity arising from the multitude of potential mutations sites and specific clinical prognostic factors, including cancer history. Revealing the factors that modulate the phenotypic heterogeneity of SOD1-ALS could prove advantageous in improving the efficacy of upcoming therapeutic approaches.}, } @article {pmid37666761, year = {2023}, author = {Li, Q and Zhang, T and Song, Y and Liu, Y and Sun, M}, title = {[A design and evaluation of wearable p300 brain-computer interface system based on Hololens2].}, journal = {Sheng wu yi xue gong cheng xue za zhi = Journal of biomedical engineering = Shengwu yixue gongchengxue zazhi}, volume = {40}, number = {4}, pages = {709-717}, pmid = {37666761}, issn = {1001-5515}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis ; *Brain-Computer Interfaces ; Quality of Life ; Event-Related Potentials, P300 ; *Wearable Electronic Devices ; }, abstract = {Patients with amyotrophic lateral sclerosis (ALS) often have difficulty in expressing their intentions through language and behavior, which prevents them from communicating properly with the outside world and seriously affects their quality of life. The brain-computer interface (BCI) has received much attention as an aid for ALS patients to communicate with the outside world, but the heavy device causes inconvenience to patients in the application process. To improve the portability of the BCI system, this paper proposed a wearable P300-speller brain-computer interface system based on the augmented reality (MR-BCI). This system used Hololens2 augmented reality device to present the paradigm, an OpenBCI device to capture EEG signals, and Jetson Nano embedded computer to process the data. Meanwhile, to optimize the system's performance for character recognition, this paper proposed a convolutional neural network classification method with low computational complexity applied to the embedded system for real-time classification. The results showed that compared with the P300-speller brain-computer interface system based on the computer screen (CS-BCI), MR-BCI induced an increase in the amplitude of the P300 component, an increase in accuracy of 1.7% and 1.4% in offline and online experiments, respectively, and an increase in the information transfer rate of 0.7 bit/min. The MR-BCI proposed in this paper achieves a wearable BCI system based on guaranteed system performance. It has a positive effect on the realization of the clinical application of BCI.}, } @article {pmid37666695, year = {2023}, author = {Duplessis, C and Clarkson, KA and Ross Turbyfill, K and Alcala, AN and Gutierrez, R and Riddle, MS and Lee, T and Paolino, K and Weerts, HP and Lynen, A and Oaks, EV and Porter, CK and Kaminski, R}, title = {GMP manufacture of Shigella flexneri 2a Artificial Invaplex (InvaplexAR) and evaluation in a Phase 1 Open-label, dose escalating study administered intranasally to healthy, adult volunteers.}, journal = {Vaccine}, volume = {41}, number = {42}, pages = {6261-6271}, doi = {10.1016/j.vaccine.2023.08.051}, pmid = {37666695}, issn = {1873-2518}, abstract = {Shigella species cause severe disease among travelers to, and children living in, endemic countries. Although significant efforts have been made to improve sanitation, increased antibiotic resistance and other factors suggest an effective vaccine is a critical need. Artificial Invaplex (InvaplexAR) is a subunit vaccine approach complexing Shigella LPS with invasion plasmid antigens. In pre-clinical studies, the InvaplexAR vaccine demonstrated increased immunogenicity as compared to the first generation product and was subsequently manufactured under cGMP for clinical testing in a first-in-human Phase 1 study. The primary objective of this study was the safety of S. flexneri 2a InvaplexAR given by intranasal (IN) immunization (without adjuvant) in a single-center, open-label, dose-escalating Phase 1 trial and secondarily to assess immunogenicity to identify a dose of InvaplexAR for subsequent clinical evaluations. Subjects received three IN immunizations of InvaplexAR, two weeks apart, in increasing dose cohorts (10 µg, 50 µg, 250 µg, and 500 μg). Adverse events were monitored using symptom surveillance, memory aids, and targeted physical exams. Samples were collected throughout the study to investigate vaccine-induced systemic and mucosal immune responses. There were no adverse events that met vaccination-stopping criteria. The majority (96%) of vaccine-related adverse events were mild in severity (most commonly nasal congestion, rhinorrhea, and post-nasal drip). Vaccination with InvaplexAR induced anti-LPS serum IgG responses and anti-Invaplex IgA and IgG antibody secreting cell (ASC) responses at vaccine doses ≥250 µg. Additionally, mucosal immune responses and functional antibody responses were seen from the serum bactericidal assay measurements. Notably, the responder rates and the kinetics of ASCs and antibody lymphocyte secretion (ALS) were similar, suggesting that either assay may be employed to identify IgG and IgA secreting cells. Further studies with InvaplexAR will evaluate alternative immunization routes, vaccination schedules and formulations to further optimize immunogenicity. (Clinical Trial Registry Number NCT02445963).}, } @article {pmid37666602, year = {2023}, author = {Chen, X and Ma, Y and Huang, M and Li, W and Zeng, D and Li, J and Wang, Y}, title = {Multiple herbicide resistance in a Cyperus difformis population in rice field from China.}, journal = {Pesticide biochemistry and physiology}, volume = {195}, number = {}, pages = {105576}, doi = {10.1016/j.pestbp.2023.105576}, pmid = {37666602}, issn = {1095-9939}, mesh = {*Oryza/genetics ; *2-Methyl-4-chlorophenoxyacetic Acid ; *Cyperus ; Herbicide Resistance/genetics ; China ; ATP-Binding Cassette Transporters ; *Acetolactate Synthase/genetics ; *Herbicides/pharmacology ; Indoleacetic Acids ; }, abstract = {Herbicide resistance is rapidly emerging in Cyperus difformis in rice fields across China. The response of a C. difformis population GX-35 was tested against five acetolactate synthase (ALS)-inhibiting herbicides, auxin herbicide MCPA and photosynthesis II (PSII)-inhibitor bentazone. Population GX-35 evolved multiple resistance to ALS-inhibiting herbicides (penoxsulam, bispyribac‑sodium, pyrazosulfuron-ethyl, halosulfuron-methly and imazapic) and auxin herbicide MCPA, with resistance levels of 140-, 1253-, 578-, 18-, 13-, and 21-fold, respectively, compared to the susceptible population. In this population, ALS gene expression was similar to that of the susceptible population. However, an Asp376Glu mutation in ALS gene was observed, leading to reduced inhibition of in-vitro ALS activities by five ALS-inhibiting herbicides. Furthermore, CYP71D8, CYP77A3, CYP78A5 and three ABC transporter genes (cluster-14412.23067, cluster-14412.25321, and cluster-14412.24716) over-expressed in absence of penoxsulam. On the other hand, an UGT73C1 and an ABC transporter (cluster-14412.25038) were induced by penoxsulam. Additionally, both over-expression and induction were observed for CYP74, CYP71A1, UGT88A1 and an ABC transporter (cluster-14412.21723). The GX-35 population has indeed evolved multiple herbicide resistance in China. Therefore, a diverse range of weed control tactics should be implemented in rice field.}, } @article {pmid37666564, year = {2023}, author = {Odland, ML and Abdul-Latif, AM and Ignatowicz, A and Bekele, A and Chu, K and Howard, A and Tabiri, S and Byiringiro, JC and Davies, J and , }, title = {Governance for injury care systems in Ghana, South Africa and Rwanda: development and pilot testing of an assessment tool.}, journal = {BMJ open}, volume = {13}, number = {9}, pages = {e074088}, pmid = {37666564}, issn = {2044-6055}, support = {130036/DH_/Department of Health/United Kingdom ; }, mesh = {Humans ; Ghana ; Rwanda ; South Africa ; Africa, Northern ; *Consensus ; }, abstract = {OBJECTIVES: This study aims to evaluate health systems governance for injury care in three sub-Saharan countries from policymakers' and injury care providers' perspectives.

SETTING: Ghana, Rwanda and South Africa.

DESIGN: Based on Siddiqi et al's framework for governance, we developed an online assessment tool for health system governance for injury with 37 questions covering health policy and implementation under 10 overarching principles of strategic vision, participation and consensus orientation, rule of law, transparency, responsiveness of institutions, equity, effectiveness or efficiency, accountability, ethics and intelligence and information. A literature review was also done to support the scoring. We derived scores using two methods-investigator scores and respondent scores.

PARTICIPANTS: The tool was sent out to purposively selected stakeholders, including policymakers and injury care providers in Ghana, Rwanda and South Africa. Data were collected between October 2020 and February 2021.

Investigator-weighted and respondent percentage scores for health system governance for injury care. This was calculated for each country in total and per principle.

RESULTS: Rwanda had the highest overall investigator-weighted percentage score (70%), followed by South Africa (59%). Ghana had the lowest overall investigator score (48%). The overall results were similar for the respondent scores. Some areas, such as participation and consensus, scored high in all three countries, while other areas, such as transparency, scored very low.

CONCLUSION: In this multicountry governance survey, we provide insight into and evaluation of health system governance for trauma in three low- and middle-income countries (LMICs) in sub-Saharan Africa. It highlights areas of improvement that need to be prioritised, such as transparency, to meet the high burden of trauma and injuries in LMICs.}, } @article {pmid37666395, year = {2023}, author = {Atiya, A and Muhsinah, AB and Alrouji, M and Alhumaydhi, FA and Al Abdulmonem, W and Aljasir, MA and Sharaf, SE and Furkan, M and Khan, RH and Shahwan, M and Shamsi, A}, title = {Unveiling promising inhibitors of superoxide dismutase 1 (SOD1) for therapeutic interventions.}, journal = {International journal of biological macromolecules}, volume = {253}, number = {Pt 2}, pages = {126684}, doi = {10.1016/j.ijbiomac.2023.126684}, pmid = {37666395}, issn = {1879-0003}, mesh = {Humans ; Superoxide Dismutase-1/genetics ; Molecular Docking Simulation ; *Amyotrophic Lateral Sclerosis/metabolism ; Oxidation-Reduction ; *Neoplasms ; Superoxide Dismutase/metabolism ; Mutation ; }, abstract = {Superoxide dismutase 1 (SOD1) is a vital enzyme responsible for controlling cellular oxidative stress. Any dysregulation of SOD1 activity is linked with cancer pathogenesis and neurodegenerative disorders, such as amyotrophic lateral sclerosis (ALS). Among the inhibitors known to be effective against SOD1, LCS-1 stands out; however, its efficacy, specificity, and safety profiles are somewhat restricted. In this study, we used PubChem library to retrieve compounds that exhibited a structural similarity of at least 90 % with LCS-1. These compounds underwent molecular docking analyses to examine their interaction patterns and binding affinities with SOD1. Further, we applied filters based on physicochemical and ADMET properties, refining the selection process. Our analysis revealed that selected compounds interact with crucial residues of SOD1 active site. To gain further insights into conformational stability and dynamics of the SOD1-ligand complexes, we conducted all-atom molecular dynamics (MD) simulations for 100 ns. We identified two compounds, CID:133306073 and CID:133446715, as potential scaffolds with promising inhibitory properties against SOD1. Both compounds hold significant potential for further exploration as therapeutic SOD1 inhibitors. Further studies are warranted to fully harness their therapeutic potential in targeting SOD1 for cancer and ALS treatment, offering new avenues for improved patient outcomes and disease management.}, } @article {pmid37664610, year = {2023}, author = {Cicardi, ME and Hallgren, JH and Mawrie, D and Krishnamurthy, K and Markandaiah, SS and Nelson, AT and Kankate, V and Anderson, EN and Pasinelli, P and Pandey, UB and Eischen, CM and Trotti, D}, title = {C9orf72 poly(PR) mediated neurodegeneration is associated with nucleolar stress.}, journal = {iScience}, volume = {26}, number = {9}, pages = {107505}, pmid = {37664610}, issn = {2589-0042}, support = {R01 NS109150/NS/NINDS NIH HHS/United States ; R21 NS090912/NS/NINDS NIH HHS/United States ; RF1 AG057882/AG/NIA NIH HHS/United States ; }, abstract = {The ALS/FTD-linked intronic hexanucleotide repeat expansion in the C9orf72 gene is aberrantly translated in the sense and antisense directions into dipeptide repeat proteins, among which poly proline-arginine (PR) displays the most aggressive neurotoxicity in-vitro and in-vivo. PR partitions to the nucleus when heterologously expressed in neurons and other cell types. We show that by lessening the nuclear accumulation of PR, we can drastically reduce its neurotoxicity. PR strongly accumulates in the nucleolus, a nuclear structure critical in regulating the cell stress response. We determined that, in neurons, PR caused nucleolar stress and increased levels of the transcription factor p53. Downregulating p53 levels also prevented PR-mediated neurotoxicity both in in-vitro and in-vivo models. We investigated if PR could induce the senescence phenotype in neurons. However, we did not observe any indications of such an effect. Instead, we found evidence for the induction of programmed cell death via caspase-3 activation.}, } @article {pmid37664457, year = {2023}, author = {Horánszky, A and Shashikadze, B and Elkhateib, R and Lombardo, SD and Lamberto, F and Zana, M and Menche, J and Fröhlich, T and Dinnyés, A}, title = {Proteomics and disease network associations evaluation of environmentally relevant Bisphenol A concentrations in a human 3D neural stem cell model.}, journal = {Frontiers in cell and developmental biology}, volume = {11}, number = {}, pages = {1236243}, pmid = {37664457}, issn = {2296-634X}, abstract = {Bisphenol A (BPA) exposure is associated with a plethora of neurodevelopmental abnormalities and brain disorders. Previous studies have demonstrated BPA-induced perturbations to critical neural stem cell (NSC) characteristics, such as proliferation and differentiation, although the underlying molecular mechanisms remain under debate. The present study evaluated the effects of a repeated-dose exposure of environmentally relevant BPA concentrations during the in vitro 3D neural induction of human induced pluripotent stem cells (hiPSCs), emulating a chronic exposure scenario. Firstly, we demonstrated that our model is suitable for NSC differentiation during the early stages of embryonic brain development. Our morphological image analysis showed that BPA exposure at 0.01, 0.1 and 1 µM decreased the average spheroid size by day 21 (D21) of the neural induction, while no effect on cell viability was detected. No alteration to the rate of the neural induction was observed based on the expression of key neural lineage and neuroectodermal transcripts. Quantitative proteomics at D21 revealed several differentially abundant proteins across all BPA-treated groups with important functions in NSC proliferation and maintenance (e.g., FABP7, GPC4, GAP43, Wnt-8B, TPPP3). Additionally, a network analysis demonstrated alterations to the glycolytic pathway, potentially implicating BPA-induced changes to glycolytic signalling in NSC proliferation impairments, as well as the pathophysiology of brain disorders including intellectual disability, autism spectrum disorders, and amyotrophic lateral sclerosis (ALS). This study enhances the current understanding of BPA-related NSC aberrations based mostly on acute, often high dose exposures of rodent in vivo and in vitro models and human GWAS data in a novel human 3D cell-based model with real-life scenario relevant prolonged and low-level exposures, offering further mechanistic insights into the ramifications of BPA exposure on the developing human brain and consequently, later life neurological disorders.}, } @article {pmid37664456, year = {2023}, author = {Garodia, P and Hegde, M and Kunnumakkara, AB and Aggarwal, BB}, title = {Curcumin, inflammation, and neurological disorders: How are they linked?.}, journal = {Integrative medicine research}, volume = {12}, number = {3}, pages = {100968}, pmid = {37664456}, issn = {2213-4220}, abstract = {BACKGROUND: Despite the extensive research in recent years, the current treatment modalities for neurological disorders are suboptimal. Curcumin, a polyphenol found in Curcuma genus, has been shown to mitigate the pathophysiology and clinical sequalae involved in neuroinflammation and neurodegenerative diseases.

METHODS: We searched PubMed database for relevant publications on curcumin and its uses in treating neurological diseases. We also reviewed relevant clinical trials which appeared on searching PubMed database using 'Curcumin and clinical trials'.

RESULTS: This review details the pleiotropic immunomodulatory functions and neuroprotective properties of curcumin, its derivatives and formulations in various preclinical and clinical investigations. The effects of curcumin on neurodegenerative diseases such as Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), brain tumors, epilepsy, Huntington's disorder (HD), ischemia, Parkinson's disease (PD), multiple sclerosis (MS), and traumatic brain injury (TBI) with a major focus on associated signalling pathways have been thoroughly discussed.

CONCLUSION: This review demonstrates curcumin can suppress spinal neuroinflammation by modulating diverse astroglia mediated cascades, ensuring the treatment of neurological disorders.}, } @article {pmid37663359, year = {2023}, author = {Gomes de Souza E Silva, EM and Tomaz da Silva, S and Januário de Holanda, L and Tezoni Borges, D and Mendonça Fernandes, AP and Evangelista Rodrigues da Silva, K and Souza Ribeiro, T and Protásio de Melo, L and de Medeiros Valentim, RA and Alves Pinto Nagem, D and Rodrigues Lindquist, AR}, title = {Effects of a self-care educational program via telerehabilitation on quality of life and caregiver burden in amyotrophic lateral sclerosis: a single-blinded randomized clinical trial protocol.}, journal = {Frontiers in psychology}, volume = {14}, number = {}, pages = {1164370}, pmid = {37663359}, issn = {1664-1078}, abstract = {INTRODUCTION: The implementation of a telerehabilitation protocol for self-care in the routine of caregivers of individuals with amyotrophic lateral sclerosis (ALS) has been associated with reduced levels of stress and improved quality of life. Moreover, it may reduce the difficulty of traveling to perform physical or other self-care activities. Thus, this study designed a clinical trial protocol to investigate the effects of a self-care education program via telerehabilitation on the burden and quality of life of caregivers of individuals with ALS.

METHODS: This single-blinded randomized clinical trial will recruit 26 caregivers and randomly allocate them to the experimental (EG = 13) or control group (CG = 13). The EG will receive an informative booklet and participate in a 6-week synchronous telerehabilitation program with a neuropsychologist, nutritionist, and physiotherapist to discuss physical and mental health. The CG will receive an informative booklet on self-care and physical activity and weekly phone calls for 6 weeks to solve questions about the booklet. Outcomes will include the caregiver burden (Zarit scale), quality of life (World Health Organization Quality of Life BREF), pain (McGill Pain Questionnaire), stress (Perceived Stress Scale), and depression (Beck Depression Inventory), which will be evaluated at the baseline after the six-week program and 30 days after the program. Additionally, we will assess daily the nocturnal awakenings, sleep patterns, level of physical activity, and heart rate variability.

DISCUSSION: This study aimed to investigate the effectiveness of telerehabilitation for caregivers of individuals with ALS. If effective, this program could be disseminated among health professionals, increasing the possibility of remotely monitoring individuals with difficulty performing physical activities.

TRIAL REGISTRATION NUMBER: NCT05884034 (clinicaltrials.gov).}, } @article {pmid37662922, year = {2023}, author = {Cao, W and Fan, D}, title = {Neutrophils: a subgroup of neglected immune cells in ALS.}, journal = {Frontiers in immunology}, volume = {14}, number = {}, pages = {1246768}, pmid = {37662922}, issn = {1664-3224}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis ; Neutrophils ; *Neurodegenerative Diseases ; Motor Neurons ; Immunity, Innate ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a chronic, progressive neurodegenerative disease characterized by the loss of motor neurons. Dysregulated peripheral immunity has been identified as a hallmark of ALS. Neutrophils, as the front-line responders of innate immunity, contribute to host defense through pathogen clearance. However, they can concurrently play a detrimental role in chronic inflammation. With the unveiling of novel functions of neutrophils in neurodegenerative diseases, it becomes essential to review our current understanding of neutrophils and to recognize the gap in our knowledge about their role in ALS. Thus, a detailed comprehension of the biological processes underlying neutrophil-induced pathogenesis in ALS may assist in identifying potential cell-based therapeutic strategies to delay disease progression.}, } @article {pmid37662623, year = {2023}, author = {Shoji, H and Sakamoto, R and Saito, C and Akino, K and Taniguchi, M}, title = {Re-survey of 16 Japanese patients with advanced-stage hereditary motor sensory neuropathy with proximal dominant involvement (HMSN-P): Painful muscle cramps for early diagnosis.}, journal = {Intractable & rare diseases research}, volume = {12}, number = {3}, pages = {198-201}, pmid = {37662623}, issn = {2186-3644}, abstract = {Hereditary motor and sensory neuropathy with proximal dominant involvement (HMSN-P) is an intractable neurological disease with autosomal dominant inheritance, four-limb weakness, sensory impairment, and a slowly progressive course. HMSN-P patients develop four-limb paralysis at the advanced-stage, as in amyotrophic lateral sclerosis (ALS). There is a natural 20- to 30-year course from initial painful muscle cramps and four-limb paralysis to respiratory dysfunction. A delay in the diagnosis of HMSN-P occurs due to the 20- to 30-year span from the initial symptom(s) to typical quadriplegia. Its early diagnosis is important, but the involvement of painful muscle cramps as an early symptom has not been clear. Following our earlier survey, we conducted a re-survey focusing on painful muscle cramps, assistive-device use, and hope for specific therapies in 16 Japanese patients with advanced-stage HMSN-P. Fifteen patients presented painful muscle cramps as the initial symptom, and muscle cramps in the lower abdomen including the flank were described by 10 of the patients. The presence of painful muscle cramps including those in the abdominal region may be a clue for the early diagnosis of HMSN-P. Painful abdominal cramps have not described in related diseases, e.g., ALS, spinal muscular atrophy, and Charcot-Marie-Tooth disease. Recent patient-welfare improvements and advances in assistive devices including robot-suit assistive limbs are delaying the terminal state of HMSN-P. Regarding specific therapies for HMSN-P, many patients choose both nucleic acid medicine and the application of induced pluripotent stem cells as a specific therapy for HMSN-P.}, } @article {pmid37662046, year = {2023}, author = {Zhu, Y and Bai, J and Li, M and Wang, H and Wang, J and Huang, X}, title = {Repetitive nerve stimulation on survival in amyotrophic lateral sclerosis.}, journal = {Frontiers in neurology}, volume = {14}, number = {}, pages = {1244385}, pmid = {37662046}, issn = {1664-2295}, abstract = {OBJECTIVE: No previous studies investigated the association between decrement of low-frequency repetitive nerve stimulation (LF-RNS) and amyotrophic lateral sclerosis (ALS) survival. We aim to study the relationship between decrement and survival in ALS.

METHODS: Sporadic ALS patients diagnosed at the Department of Neurology, the First Medical Center, Chinese PLA General Hospital from January 2018 to December 2019 were enrolled in this study. Experienced neurologists followed up the participants regularly every 6 months until January 2022. A decremental response of 10% or greater at least in one muscle was considered positive. According to the decrement, the participants were divided into LF-RNS (+) and LF-RNS (-) groups.

RESULTS: One hundred and eighty-one sporadic ALS patients were recruited in our study, including 100 males and 81 females. Among them, 10 cases (5.5%) were lost to follow-up, 99 cases (54.7%) died, and 72 patients (39.8%) were still alive at the last follow-up. The median survival time of all ALS patients in this study was 42.0 months. There was no significant difference of median survival in LF-RNS(+) group and LF-RNS(-) group (p = 0.159, Kaplan-Meier method). In multivariate Cox regression analysis, age of onset, diagnostic delay, and ALS Functional Rating Scale-Revised (ALSFRS-R) score were associated with ALS survival, but the decrement was not correlated with ALS survival (p = 0.238).

CONCLUSION: The decrement in accessory and ulnar nerves was not associated with the survival of ALS. The decrement of LF-RNS could not be an electrophysiological marker to predict ALS survival.}, } @article {pmid37661426, year = {2023}, author = {Conroy, E and Vélez-Gómez, B and O'Brien, D and Heverin, M and Hardiman, O and Mcdermott, C and Galvin, M}, title = {IMPACT-ALS: summary of results from a European survey of people living with ALS.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {}, number = {}, pages = {1-10}, doi = {10.1080/21678421.2023.2249515}, pmid = {37661426}, issn = {2167-9223}, abstract = {OBJECTIVE: The IMPACT-ALS survey collected the experiences of people living with ALS (plwALS) across nine European countries. We aimed to better understand the functional burden of ALS to ensure the experiences of plwALS inform the development of person-centered therapies.

METHODS: The content was informed by the US IMPACT-ALS survey, with adjustments relevant to the European population. Questionnaires consisted of four modules, each of which was pilot tested in advance of distribution. Data were captured using the Qualtrics software and were analyzed in SPSS.

RESULTS: 857 respondents completed the survey, with a participation rate ranging from 0.2% to 6.3% across the nine participating countries. The majority were male and aged 55-74 years old. In the previous 2 weeks, symptoms experienced included weakness (81%), fatigue (61%), speech impairment (38%), pain (27%), and depression and other mood changes (23%). Eighty-two percent of respondents reported fears, of which the most common were leaving family too soon (68%) and death from respiratory failure (50%). Lifestyle changes since diagnosis were reported by 89% of respondents, with less time spent doing most daily activities but more time on the internet (81%), reading (56%) and communicating with family and friends (55%). Stopping progression of ALS was the most desired impact for a new therapy for 68% respondents.

CONCLUSIONS: The European IMPACT-ALS survey has generated insights into the complex experiences of plwALS. The data provide unique patient perspectives on common symptoms, fears, functional limitations, lifestyle changes, and wishes for future therapies that will enhance patient-centric care in ALS.}, } @article {pmid37660686, year = {2023}, author = {Bhakta, P and Dutta, A}, title = {Homeopathic Treatment of Ramsay Hunt Syndrome: A Case Report.}, journal = {Complementary medicine research}, volume = {30}, number = {6}, pages = {544-552}, doi = {10.1159/000533849}, pmid = {37660686}, issn = {2504-2106}, mesh = {Female ; Humans ; Young Adult ; Adult ; *Facial Paralysis ; *Homeopathy ; *Herpes Zoster Oticus/therapy ; *Deglutition Disorders ; Quality of Life ; Ulcer ; }, abstract = {INTRODUCTION: Ramsay Hunt syndrome (RHS) is an uncommon neurological complication resulting from the reactivation of latent herpes zoster virus. The condition often presents with facial paralysis, palatal ulcers, dysphagia, and altered taste sensation, leading to reduced quality of life. Standard therapeutic options for RHS have limitations, prompting the exploration of alternative treatments with improved prognostic outcomes. This case report aims to present a noteworthy clinical observation of RHS managed with individualized homeopathic treatment, emphasizing its potential therapeutic effect.

CASE DESCRIPTION: A 24-year-old female patient exhibited left-sided facial weakness, along with palatal ulcers, dysphagia, and ageusia, prompting the diagnosis of RHS. Following the principles of homeopathy, a personalized therapeutic regimen was formulated, consisting tailored administration of Rhus toxicodendron, Spigelia anthelmia, and Sulfur. The House-Brackmann scale was employed to objectively assess the severity of facial palsy, while photographic documentation tracked the progression of palatal ulcers and facial paralysis. Over a carefully monitored observation period of 14 days, the patient demonstrated notable therapeutic response. There was a significant reduction in the extent of palatal ulceration and left-sided facial palsy exhibited marked improvement. Subsequent days of follow-up witnessed a consistent amelioration of the patient's condition, substantiating the effect of the individualized homeopathic treatment.

CONCLUSION: This case report highlights an exceptional instance of RHS recovery within a relatively short timeframe, achieved through the administration of individualized homeopathic therapy. The favorable outcomes observed in this case underscore the potential of homeopathy as a promising intervention for RHS management. Nevertheless, further systematic investigations are imperative to comprehensively evaluate the scope and applicability of homeopathy in the treatment of RHS.

UNLABELLED: EinleitungDas Ramsay‐Hunt‐Syndrom (RHS) ist eine seltene neurologische Komplikation, die durch die Reaktivierung einer latenten Herpes‐Zoster‐Virusinfektion verursacht wird. Die Krankheit manifestiert sich häufig mit Gesichtslähmung, Ulcerationen am Gaumen, Dysphagie und verändertem Geschmacksempfinden und ist mit einer Einschränkung der Lebensqualität verbunden. Die Standardtherapieoptionen für RHS sind begrenzt, weshalb nach alternativen Behandlungsmöglichkeiten mit besseren prognostischen Ergebnissen gesucht wird. Im vorliegenden Fallbericht wird eine interessante klinische Beobachtung bei RHS vorgestellt, das mit individualisierter Homöopathie behandelt wurde, und deren potenzielle therapeutische Wirksamkeit wird hervorgehoben.Der FallEine 24-jährige Patientin zeigte eine linksseitige Gesichtsschwäche in Verbindung mit Ulcerationen am Gaumen, Dysphagie und Ageusie, so dass die Diagnose RHS gestellt wurde. Gemäß den Prinzipien der Homöopathie wurde ein personalisiertes Therapieschema formuliert, das die individuell zugeschnittene Gabe von Rhus toxicodendron, Spigelia anthelmia, und Sulphur umfasste. Die objektive Bewertung des Schweregrads der Gesichtslähmung erfolgte mithilfe der House-Brackmann-Skala, wohingegen das Fortschreiten der Gaumenulcerationen und der Gesichtslähmung fotografisch dokumentiert wurde. Während eines sorgfältig überwachten Beobachtungszeitraums von 14 Tagen zeigte die Patientin ein deutliches therapeutisches Ansprechen. Das Ausmaß der Gaumenulcerationen ging signifikant zurück, und die linksseitige Gesichtslähmung besserte sich deutlich. In den folgenden Tagen besserte sich der Zustand der Patientin kontinuierlich, was die Wirkung der individualisierten homöopathischen Behandlung untermauert.SchlussfolgerungDieser Fallbericht beleuchtet einen ungewöhnlichen Fall von Genesung nach einem RHS innerhalb relativ kurzer Zeit, die durch Verabreichung einer individualisierten homöopathischen Therapie erreicht wurde. Die im vorliegenden Fall beobachteten günstigen Ergebnisse unterstreichen das Potenzial der Homöopathie als vielversprechende Intervention zur Behandlung von RHS. Allerdings sind weitere systematische Untersuchungen unabdingbar, um den Umfang und die Anwendbarkeit der Homöopathie bei der Behandlung von RHS umfassend zu beurteilen.}, } @article {pmid37658972, year = {2023}, author = {Singh, S and Shukla, R}, title = {Nanovesicular-Mediated Intranasal Drug Therapy for Neurodegenerative Disease.}, journal = {AAPS PharmSciTech}, volume = {24}, number = {7}, pages = {179}, pmid = {37658972}, issn = {1530-9932}, mesh = {Humans ; *Neurodegenerative Diseases/drug therapy ; Nose ; Drug Delivery Systems ; Brain ; *Glioblastoma ; }, abstract = {Numerous neurodegenerative conditions, such as Alzheimer's, Huntington's, Parkinson's, amyotrophic lateral sclerosis, and glioblastoma multiform are now becoming significant concerns of global health. Formulation-related issues, physiological and anatomical barriers, post-administration obstacles, physical challenges, regulatory limitations, environmental hurdles, and health and safety issues have all hindered successful delivery and effective outcomes despite a variety of treatment options. In the current review, we covered the intranasal route, an alternative strategic route targeting brain for improved delivery across the BBB. The trans-nasal pathway is non-invasive, directing therapeutics directly towards brain, circumventing the barrier and reducing peripheral exposure. The delivery of nanosized vesicles loaded with drugs was also covered in the review. Nanovesicle systems are organised in concentric bilayered lipid membranes separated with aqueous layers. These carriers surmount the disadvantages posed by intranasal delivery of rapid mucociliary clearance and enzymatic degradation, and enhance retention of drug to reach the site of target. In conclusion, the review covers in-depth conclusions on numerous aspects of formulation of drug-loaded vesicular system delivery across BBB, current marketed nasal devices, significant jeopardies, potential therapeutic aids, and current advancements followed by future perspectives.}, } @article {pmid37660155, year = {2023}, author = {Chandhok, S and Pereira, L and Momchilova, EA and Marijan, D and Zapf, R and Lacroix, E and Kaur, A and Keymanesh, S and Krieger, C and Audas, TE}, title = {Stress-mediated aggregation of disease-associated proteins in amyloid bodies.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {14471}, pmid = {37660155}, issn = {2045-2322}, support = {PJT-162364//CIHR/Canada ; }, mesh = {Humans ; Diclofenac/pharmacology ; Amyloidogenic Proteins ; *Amyloidosis ; Prostaglandin-Endoperoxide Synthases ; *Immunoglobulin Light-chain Amyloidosis ; }, abstract = {The formation of protein aggregates is a hallmark of many neurodegenerative diseases and systemic amyloidoses. These disorders are associated with the fibrillation of a variety of proteins/peptides, which ultimately leads to cell toxicity and tissue damage. Understanding how amyloid aggregation occurs and developing compounds that impair this process is a major challenge in the health science community. Here, we demonstrate that pathogenic proteins associated with Alzheimer's disease, diabetes, AL/AA amyloidosis, and amyotrophic lateral sclerosis can aggregate within stress-inducible physiological amyloid-based structures, termed amyloid bodies (A-bodies). Using a limited collection of small molecule inhibitors, we found that diclofenac could repress amyloid aggregation of the β-amyloid (1-42) in a cellular setting, despite having no effect in the classic Thioflavin T (ThT) in vitro fibrillation assay. Mapping the mechanism of the diclofenac-mediated repression indicated that dysregulation of cyclooxygenases and the prostaglandin synthesis pathway was potentially responsible for this effect. Together, this work suggests that the A-body machinery may be linked to a subset of pathological amyloidosis, and highlights the utility of this model system in the identification of new small molecules that could treat these debilitating diseases.}, } @article {pmid37659835, year = {2023}, author = {Bermudo Fuenmayor, S and Serrano Castro, PJ and Quiroga Subirana, P and López Palmero, S and Requena Mullor, M and Parrón Carreño, T}, title = {Environmental exposure to pesticides and Amyotrophic Lateral Sclerosis in the South of Spain.}, journal = {Neurologia}, volume = {38}, number = {7}, pages = {447-452}, doi = {10.1016/j.nrleng.2021.01.004}, pmid = {37659835}, issn = {2173-5808}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/chemically induced/epidemiology ; *Pesticides/adverse effects ; Spain/epidemiology ; Case-Control Studies ; Environmental Exposure/adverse effects ; }, abstract = {OBJECTIVE: To determine if there is a relationship between environmental exposure to pesticides and the prevalence of Amyotrophic Lateral Sclerosis (ALS) in Andalusia.

METHOD: We carried out a case-control study using the logistic regression method to verify the relationship between the prevalence of ALS in the area exposed to pesticides versus the unexposed area, through the Odds Ratio statistical test.

RESULTS: The study population consisted of 519 individuals diagnosed with ALS between January 2016 and December 2018 according to the CMBD (Minimum Basic Data Set) as cases. In the control group, we have 8,384,083 individuals obtained from data from the National Institute of Statistics (INE). The Odds Ratio (OR) was used as a measure of association between cases and controls, obtaining an OR between 0.76 and 1.08 for the confidence interval of the CI (95%).

CONCLUSIONS: Despite the existence of various studies that suggest a possible association between environmental exposure to pesticides and the risk of Amyotrophic Lateral Sclerosis, our analysis of the Andalusian population did not find significant evidence of this association.}, } @article {pmid37659173, year = {2023}, author = {Hirayama, T and Shibukawa, M and Morioka, H and Hozumi, M and Tsuda, H and Atsuta, N and Izumi, Y and Nakayama, Y and Shimizu, T and Inoue, H and Urushitani, M and Yamanaka, K and Aoki, M and Ebihara, S and Takeda, A and Kano, O}, title = {The necessity to improve disaster preparedness among patients with amyotrophic lateral sclerosis and their families.}, journal = {Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia}, volume = {116}, number = {}, pages = {87-92}, doi = {10.1016/j.jocn.2023.08.002}, pmid = {37659173}, issn = {1532-2653}, mesh = {Humans ; Male ; Middle Aged ; Aged ; *Amyotrophic Lateral Sclerosis/therapy ; Communication ; *Disasters ; Educational Status ; Japan ; }, abstract = {Disaster preparation is an important issue for patients with amyotrophic lateral sclerosis (ALS). However, to the best of our knowledge, no studies have investigated disaster preparedness among patients with ALS. In this study, we aimed to investigate disaster preparation in patients with ALS and their caregivers, including their families, in Japan. We conducted a nationwide webinar in September 2022 titled "ALS Café" and distributed a self-report questionnaire to participants with questions about awareness of disaster preparedness, social countermeasures, stockpiles, and electricity demand. Forty-eight patients with ALS (27 male; average age 60.0 ± 9.3 years) and 23 caregivers (8 male; 55.7 ± 9.9 years) responded. The median revised ALS Functional Rating Scale score was 30.5, and 25% of the patients with ALS were on a ventilator. More than 70% of the respondents answered that they were not prepared for disasters, increasing to 89% in patients not using ventilators. In the event of their phones being down, 86% of the respondents had no plans for alternative means of communication. <30% of the respondents, including ventilator users, had secured human resources for transportation. Twenty-five percent of the respondents did not stockpile food and beverages, and 12% of the ventilator users had no government-recommended ventilator preparation equipment. Thus, although patients with ALS and their families with ventilators have a high awareness of disaster preparedness, their awareness remains insufficient. Furthermore, patients with ALS and their families without ventilators have a low awareness of disaster preparedness. Therefore, better education regarding disaster preparedness is necessary for these groups.}, } @article {pmid37658515, year = {2024}, author = {Howe, SL and Holdom, CJ and McCombe, PA and Henderson, RD and Zigman, JM and Ngo, ST and Steyn, FJ}, title = {Associations of postprandial ghrelin, liver-expressed antimicrobial peptide 2 and leptin levels with body composition, disease progression and survival in patients with amyotrophic lateral sclerosis.}, journal = {European journal of neurology}, volume = {31}, number = {1}, pages = {e16052}, pmid = {37658515}, issn = {1468-1331}, support = {R01 DK103884/DK/NIDDK NIH HHS/United States ; /NH/NIH HHS/United States ; }, mesh = {Humans ; *Leptin/metabolism ; Ghrelin/metabolism ; *Amyotrophic Lateral Sclerosis ; Hepcidins/metabolism ; Prospective Studies ; Delayed Diagnosis ; Body Weight ; Disease Progression ; Body Composition ; }, abstract = {BACKGROUND AND PURPOSE: Loss of appetite contributes to weight loss and faster disease progression in amyotrophic lateral sclerosis (ALS). Impairment of appetite control in ALS may include altered production or action of orexigenic (i.e., ghrelin) and anorexigenic (i.e., liver-expressed antimicrobial peptide 2 [LEAP2] and leptin) hormones. We aimed to determine if postprandial circulating ghrelin levels, LEAP2 levels, LEAP2:ghrelin molar ratio and leptin levels differ in ALS patients compared to non-neurodegenerative disease controls, and whether they are associated with disease progression and body composition.

METHODS: In this prospective natural history study, we assessed postprandial plasma levels of ghrelin, LEAP2 and leptin in patients with ALS (cases; n = 46) and controls (controls; n = 43). For cases, measures were compared to changes in body weight, body composition and clinical outcomes.

RESULTS: Postprandial ghrelin level was decreased by 52% in cases compared to controls (p = 0.013). LEAP2:ghrelin molar ratio was increased by 249% (p = 0.009), suggesting greater ghrelin resistance. Patients with lower LEAP2:ghrelin tended to have better functional capacity at assessment, as inferred by the ALS Functional Rating Scale-Revised (τ = -0.179, p = 0.086). Furthermore, ghrelin and LEAP2:ghrelin molar ratio correlated with diagnostic delay (ghrelin, τ = 0.223, p = 0.029; LEAP2:ghrelin, τ = -0.213, p = 0.037). Baseline ghrelin level, LEAP2 level, LEAP2:ghrelin ratio and leptin level were, however, not predictive of change in functional capacity during follow-up. Also, patients with higher postprandial ghrelin levels (hazard ratio [HR] 1.375, p = 0.048), and lower LEAP2:ghelin ratios (HR 0.828, p = 0.051) had an increased risk of earlier death.

CONCLUSIONS: Reduced postprandial ghrelin levels, coupled with increased LEAP2:ghrelin molar ratios, suggests a loss of ghrelin action in patients with ALS. Given ghrelin's actions on appetite, metabolism and neuroprotection, reduced ghrelin and greater ghrelin resistance could contribute to impaired capacity to tolerate the physiological impact of disease. Comprehensive studies are needed to explain how ghrelin and LEAP2 contribute to body weight regulation and disease progression in ALS.}, } @article {pmid37657967, year = {2023}, author = {Ryan, SK and Ugalde, CL and Rolland, AS and Skidmore, J and Devos, D and Hammond, TR}, title = {Therapeutic inhibition of ferroptosis in neurodegenerative disease.}, journal = {Trends in pharmacological sciences}, volume = {44}, number = {10}, pages = {674-688}, doi = {10.1016/j.tips.2023.07.007}, pmid = {37657967}, issn = {1873-3735}, support = {MC_PC_19032/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Humans ; *Ferroptosis ; *Neurodegenerative Diseases/drug therapy ; Iron ; }, abstract = {Iron accumulation has been associated with the etiology and progression of multiple neurodegenerative diseases (NDDs). The exact role of iron in these diseases is not fully understood, but an iron-dependent form of regulated cell death called ferroptosis could be key. Although there is substantial preclinical and clinical evidence that ferroptosis plays a role in NDD, there are still questions regarding how to target ferroptosis therapeutically, including which proteins to target, identification of clinically relevant biomarkers, and which patients might benefit most. Clinical trials of iron- and ferroptosis-targeted therapies are beginning to provide some answers, but there is growing interest in developing new ferroptosis inhibitors. We describe newly identified ferroptosis targets, opportunities, and challenges in NDD, as well as key considerations for progressing new therapeutics to the clinic.}, } @article {pmid37657945, year = {2023}, author = {Cristi, AC and Rapuri, S and Coyne, AN}, title = {Nuclear pore complex and nucleocytoplasmic transport disruption in neurodegeneration.}, journal = {FEBS letters}, volume = {597}, number = {20}, pages = {2546-2566}, pmid = {37657945}, issn = {1873-3468}, support = {R00 NS123242/NS/NINDS NIH HHS/United States ; R01 NS132836/NS/NINDS NIH HHS/United States ; }, mesh = {Humans ; *Nuclear Pore/metabolism ; Active Transport, Cell Nucleus/physiology ; Nuclear Envelope ; Nuclear Pore Complex Proteins/genetics/metabolism ; Endosomal Sorting Complexes Required for Transport/genetics/metabolism ; *Neurodegenerative Diseases/metabolism ; }, abstract = {Nuclear pore complexes (NPCs) play a critical role in maintaining the equilibrium between the nucleus and cytoplasm, enabling bidirectional transport across the nuclear envelope, and are essential for proper nuclear organization and gene regulation. Perturbations in the regulatory mechanisms governing NPCs and nuclear envelope homeostasis have been implicated in the pathogenesis of several neurodegenerative diseases. The ESCRT-III pathway emerges as a critical player in the surveillance and preservation of well-assembled, functional NPCs, as well as nuclear envelope sealing. Recent studies have provided insights into the involvement of nuclear ESCRT-III in the selective reduction of specific nucleoporins associated with neurodegenerative pathologies. Thus, maintaining quality control of the nuclear envelope and NPCs represents a pivotal element in the pathological cascade leading to neurodegenerative diseases. This review describes the constituents of the nuclear-cytoplasmic transport machinery, encompassing the nuclear envelope, NPC, and ESCRT proteins, and how their structural and functional alterations contribute to the development of neurodegenerative diseases.}, } @article {pmid37657764, year = {2023}, author = {Zhou, S and Zhou, Y and Zhong, W and Su, Z and Qin, Z}, title = {Involvement of protein L-isoaspartyl methyltransferase in the physiopathology of neurodegenerative diseases: Possible substrates associated with synaptic function.}, journal = {Neurochemistry international}, volume = {170}, number = {}, pages = {105606}, doi = {10.1016/j.neuint.2023.105606}, pmid = {37657764}, issn = {1872-9754}, mesh = {Humans ; *Protein D-Aspartate-L-Isoaspartate Methyltransferase/metabolism ; *Neurodegenerative Diseases/metabolism ; Proteins/metabolism ; Isoaspartic Acid/metabolism ; Aspartic Acid/metabolism ; }, abstract = {Synaptic dysfunction is a typical pathophysiologic change in neurodegenerative diseases (NDs) such as Alzheimer's disease (AD), Parkinson's disease (PD), Hintington's disease (HD) and amyotrophic lateral sclerosis (ALS), which involves protein post-translational modifications (PTMs) including L-isoaspartate (L-isoAsp) formed by isomerization of aspartate or deamidation of asparagine. The formation of L-isoAsp could be repaired by protein L-isoaspartyl methyltransferase (PIMT). Some synaptic proteins have been identified as PIMT potential substrates and play an essential role in ensuring synaptic function. In this review, we discuss the role of certain synaptic proteins as PIMT substrates in neurodegenerative disease, thus providing therapeutic synapse-centered targets for the treatment of NDs.}, } @article {pmid37654673, year = {2023}, author = {Fischetti, F and Poli, L and De Tommaso, M and Paolicelli, D and Greco, G and Cataldi, S}, title = {The role of exercise parameters on small extracellular vesicles and microRNAs cargo in preventing neurodegenerative diseases.}, journal = {Frontiers in physiology}, volume = {14}, number = {}, pages = {1241010}, pmid = {37654673}, issn = {1664-042X}, abstract = {Physical activity (PA), which includes exercise, can reduce the risk of developing various non-communicable diseases, including neurodegenerative diseases (NDs), and mitigate their adverse effects. However, the mechanisms underlying this ability are not yet fully understood. Among several possible mechanisms proposed, such as the stimulation of brain-derived neurotrophic factor (BDNF), endothelial nitric oxide synthase (eNOS), insulin-like growth factor-1 (IGF-1), vascular endothelial growth factor (VEGF), and nerve growth factor (NGF), the possible involvement of particular vesicular structures enclosed in lipid membranes known as extracellular vesicles (EVs) has recently been investigated. These EVs would appear to exert a paracrine and systemic action through their ability to carry various molecules, particularly so-called microRNAs (miRNAs), performing a function as mediators of intercellular communication. Interestingly, EVs and miRNAs are differentially expressed following PA, but evidence on how different exercise parameters may differentially affect EVs and the miRNAs they carry is still scarce. In this review we summarized the current human findings on the effects of PA and different exercise parameters exerted on EVs and their cargo, focusing on miRNAs molecules, and discussing how this may represent one of the biological mechanisms through which exercise contributes to preventing and slowing NDs.}, } @article {pmid37653823, year = {2023}, author = {Oh, SH and Jin, HS and Park, CH}, title = {Risk factors and neonatal outcomes of pulmonary air leak syndrome in extremely preterm infants: A nationwide descriptive cohort study.}, journal = {Medicine}, volume = {102}, number = {34}, pages = {e34759}, pmid = {37653823}, issn = {1536-5964}, mesh = {Female ; Humans ; Infant, Newborn ; Pregnancy ; Cohort Studies ; *Infant, Extremely Premature ; Prospective Studies ; Risk Factors ; Salts ; Sodium Chloride ; Sodium Chloride, Dietary ; *Lung Diseases ; Syndrome ; }, abstract = {Most extremely preterm infants (EPIs), who were born before 28 weeks of gestation, with pulmonary air leak syndrome (ALS) are symptomatic, often severe, and require drainage. EPIs with severe air leak syndrome (sALS) that require tube drainage or needle aspiration are at high risk of morbidities and mortality. This study aimed to investigate perinatal characteristics, morbidities, and mortality in EPIs with sALS, and to estimate the risk of mortality according to gestational age (GA). A prospective cohort study conducted from 2013 to 2020 compiled the Korean Neonatal Network database to evaluate the incidence, perinatal characteristics, and outcomes of sALS in EPIs born before 28 weeks of gestation. Among 5666 EPIs, the incidence of sALS was 9.4% and inversely related to GA. From this cohort, we compared 532 EPIs with sALS to 1064 EPIs without sALS as controls, matching the subjects by GA and birth weight. Preterm premature rupture of membranes, oligohydramnios, resuscitation after birth, low Apgar scores, repeated surfactant administration, persistent pulmonary hypertension of the newborn, and pulmonary hemorrhage were associated with the development of pneumothorax. The sALS group required a higher fraction of inspired oxygen and more invasive respiratory support at both 28 days of life and 36 weeks of postmenstrual age. The sALS group had a higher incidence of bronchopulmonary dysplasia and major brain injury. The mortality rate was higher in the sALS group than in the control group (55.3% vs 32.5%, P < .001), and the ALS group had a 1.7 times risk of mortality than the control group. More attention should be paid to sALS in EPIs because the frequency of sALS increased as GA decreased, and the risk of mortality was more significant at lower GA.}, } @article {pmid37651908, year = {2024}, author = {Câmara, ABF and da Silva, WJO and Neves, ACO and Moura, HOMA and de Lima, KMG and de Carvalho, LS}, title = {Excitation-emission fluorescence spectroscopy coupled with PARAFAC and MCR-ALS with area correlation for investigation of jet fuel contamination.}, journal = {Talanta}, volume = {266}, number = {Pt 2}, pages = {125126}, doi = {10.1016/j.talanta.2023.125126}, pmid = {37651908}, issn = {1873-3573}, abstract = {The contamination of jet fuel has gained attention in the past years as a notable factor in aircraft accidents. Identifying the contamination sources is still a challenge, especially when they have a similar composition to the fuel, such as kerosene solvent (KS). A novel analytical methodology was developed by combining a set of excitation-emission matrix (EEM) fluorescence to area constrained multivariate curve resolution with alternating least-squares (MCR-ALS) and PARAllel FACtor (PARAFAC) analysis, in order to identify KS in blends with JET-A1. For this purpose, a dataset with 50 samples (KS and JET-A1 blends, 2.0-100% v/v) was used to build the multivariate models. Both PARAFAC and MCR-ALS allowed fuel quantification with 4.64% and 3.46% RMSEP, respectively; both models (PARAFAC and MCR-ALS) could quantify KS with high accuracy (RMSEP <5.36%). In addition, MCR-ALS model was able to recover the pure spectral profiles of KS, JET-A1 and interferers. GC-MS data of the samples proved the composition similarities between both petroleum distillates, thus being inefficient for identifying the contamination. These results indicate that the development of multivariate models using EEM was the key for contributing with a new low-cost and accurate method for on-line screening of jet fuel contamination.}, } @article {pmid37651612, year = {2023}, author = {Sadžak, A and Eraković, M and Šegota, S}, title = {Kinetics of Flavonoid Degradation and Controlled Release from Functionalized Magnetic Nanoparticles.}, journal = {Molecular pharmaceutics}, volume = {20}, number = {10}, pages = {5148-5159}, doi = {10.1021/acs.molpharmaceut.3c00478}, pmid = {37651612}, issn = {1543-8392}, abstract = {Flavonoids are naturally occurring antioxidants that have been shown to protect cell membranes from oxidative stress and have a potential use in photodynamic cancer treatment. However, they degrade at physiological pH values, which is often neglected in drug release studies. Kinetic study of flavonoid oxidation can help to understand the mechanism of degradation and to correctly analyze flavonoid release data. Additionally, the incorporation of flavonoids into magnetic nanocarriers can be utilized to mitigate degradation and overcome their low solubility, while the release can be controlled using magnetic fields (MFs). An approach that combines alternating least squares (ALS) and multilinear regression to consider flavonoid autoxidation in release studies is presented. This approach can be used in general cases to account for the degradation of unstable drugs released from nanoparticles. The oxidation of quercetin, myricetin (MCE), and myricitrin (MCI) was studied in PBS buffer (pH = 7.4) using UV-vis spectrophotometry. ALS was used to determine the kinetic profiles and characteristic spectra, which were used to analyze UV-vis data of release from functionalized magnetic nanoparticles (MNPs). MNPs were selected for their unique magnetic properties, which can be exploited for both targeted drug delivery and control over the drug release. MNPs were prepared and characterized by X-ray diffraction, infrared spectroscopy, scanning electron microscopy, superconducting quantum interference device magnetometer, and electrophoretic mobility measurements. Autoxidation of all three flavonoids follows a two-step first-order kinetic model. MCE showed the fastest degradation, while the oxidation of MCI was the slowest. The flavonoids were successfully loaded into the prepared MNPs, and the drug release was described by the first-order and Korsmeyer-Peppas models. External MFs were utilized to control the release mechanism and the cumulative mass of the flavonoids released.}, } @article {pmid37651420, year = {2023}, author = {Williams, W and Theron, E and Khan, W and Stassen, W}, title = {Developing a South African curriculum for education in neonatal critical care retrieval: An initial exploration.}, journal = {PloS one}, volume = {18}, number = {8}, pages = {e0290972}, pmid = {37651420}, issn = {1932-6203}, mesh = {Infant, Newborn ; Humans ; South Africa ; Retrospective Studies ; Educational Status ; *Curriculum ; *Critical Care ; }, abstract = {BACKGROUND: Owing to limited or centralised neonatal critical care resources, the interfacility transfer of neonates is inevitable. In many high-income settings, dedicated Critical Care Retrieval Services (CCRS) with additional education and training undertake neonatal critical care retrieval (CCR). In South Africa, however, these transfers are mostly conducted by advanced paramedics with limited education in neonatal care, and this may lead to high adverse event rates. In SA, a shortage of skilled neonatal interfacility transport services has been identified as one of the top ten avoidable causes of under-5 mortality. In order to address this gap in neonatal transfer education for paramedics in South Africa, the aim of this study is to develop a curriculum for neonatal critical care retrieval in South Africa.

METHODS: Using Kern's approach to curriculum development, a general and targeted needs assessment was conducted through semi-structured interviews with experts in the field and a focus group discussion with a prospective student group. Interviews were preceded and informed by a literature review and retrospective chart review of neonates who underwent CCR in SA over a one-year period. Audio recordings of interviews were transcribed verbatim and subjected to inductive-dominant content analysis. Finally, qualitative codes were expanded into course outcome and a curriculum map was developed.

RESULTS: Six experts in neonatal critical care and retrieval participated in semi-structured interviews with a mean duration of 59 minutes. Following transcription and analysis, 372 codes were developed. Seven prehospital providers (prospective students) who are involved in neonatal transfers in South Africa participated in a focus group discussion with a duration of 91 minutes. The audio recording was transcribed and analysed with 97 codes extracted. The main categories were: Current status of neonatal CCR in South Africa; learning and education in neonatal CCR; and proposed curriculum structure. The proposed curriculum structure described 13 broad course outcomes to be delivered as a blended postgraduate programme. Participants noted that funding, employer buy-in and internet resources would be required. The targeted prospective student group should be all Advanced Life Support (ALS) providers with a change in their scope of practice on completion.

CONCLUSION: This study described the need for additional education in neonatal critical care retrieval due to the limitations in the current and past education systems. This study provides a curriculum structure with course outcomes that can be used as a basis for the development of a complete curriculum for education in neonatal CCR, with the potential to greatly reduce adverse event rates.}, } @article {pmid37651231, year = {2023}, author = {Held, A and Adler, M and Marques, C and Reyes, CJ and Kavuturu, AS and Quadros, ARAA and Ndayambaje, IS and Lara, E and Ward, M and Lagier-Tourenne, C and Wainger, BJ}, title = {iPSC motor neurons, but not other derived cell types, capture gene expression changes in postmortem sporadic ALS motor neurons.}, journal = {Cell reports}, volume = {42}, number = {9}, pages = {113046}, pmid = {37651231}, issn = {2211-1247}, support = {RF1 NS127407/NS/NINDS NIH HHS/United States ; RF1 NS124203/NS/NINDS NIH HHS/United States ; DP2 NS106664/NS/NINDS NIH HHS/United States ; R01 NS112503/NS/NINDS NIH HHS/United States ; F32 NS114319/NS/NINDS NIH HHS/United States ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/pathology ; *Induced Pluripotent Stem Cells/metabolism ; Motor Neurons/metabolism ; Gene Expression ; DNA-Binding Proteins/metabolism ; }, abstract = {Motor neuron degeneration, the defining feature of amyotrophic lateral sclerosis (ALS), is a primary example of cell-type specificity in neurodegenerative diseases. Using isogenic pairs of induced pluripotent stem cells (iPSCs) harboring different familial ALS mutations, we assess the capacity of iPSC-derived lower motor neurons, sensory neurons, astrocytes, and superficial cortical neurons to capture disease features including transcriptional and splicing dysregulation observed in human postmortem neurons. At early time points, differentially regulated genes in iPSC-derived lower motor neurons, but not other cell types, overlap with one-third of the differentially regulated genes in laser-dissected motor neurons from ALS compared with control postmortem spinal cords. For genes altered in both the iPSC model and bona fide human lower motor neurons, expression changes correlate between the two populations. In iPSC-derived lower motor neurons, but not other derived cell types, we detect the downregulation of genes affected by TDP-43-dependent splicing. This reduction takes place exclusively within genotypes known to involve TDP-43 pathology.}, } @article {pmid37650499, year = {2023}, author = {Morichon, L and Hirtz, C and Tiers, L and Mezghrani, A and Raoul, C and Esselin, F and La Cruz, E and Julien, JP and Camu, W and Lehmann, S}, title = {Ultrasensitive digital immunoassays for SOD1 conformation in amyotrophic lateral sclerosis.}, journal = {Bioanalysis}, volume = {15}, number = {15}, pages = {927-936}, doi = {10.4155/bio-2023-0103}, pmid = {37650499}, issn = {1757-6199}, support = {misSOD1//ARSLA: Association pour la recherche sur la SLA/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis ; Superoxide Dismutase-1 ; Biological Assay ; Immunoassay ; Molecular Conformation ; }, abstract = {Aim: The aim of this study was to detect misfolded Cu/Zn SOD1 as a potential biomarker for amyotrophic lateral sclerosis (ALS). Materials & methods: Two ultrasensitive immunodetection assays were developed for the quantification of total and misfolded SOD1. Results: The detection of total and misfolded SOD1 was possible in human serum and cerebrospinal fluid. Total SOD1 was increased in cerebrospinal fluid from ALS patients. Misfolded SOD1 had low and variable expression in both control and ALS patient samples. Conclusion: These assays hold promise for improving our understanding of ALS and its detection, and could lead to more effective treatment options in the future. Further studies in larger cohorts are now required.}, } @article {pmid37650100, year = {2023}, author = {De Marchi, F and Ferraro, PM and Introna, A and Spinelli, EG}, title = {Editorial: What's next? Innovative translational markers across the ALS-FTD continuum.}, journal = {Frontiers in neuroscience}, volume = {17}, number = {}, pages = {1250127}, pmid = {37650100}, issn = {1662-4548}, } @article {pmid37649875, year = {2023}, author = {Shrestha, R and Indrasena, BSH and Subedi, P and Lamsal, D and Moulton, C and Aylott, J}, title = {Evaluation of junior doctors' retention of knowledge and skills after simulation training in shockable rhythm cardiac arrest in a low-resource setting in Nepal.}, journal = {Resuscitation plus}, volume = {15}, number = {}, pages = {100448}, pmid = {37649875}, issn = {2666-5204}, abstract = {AIMS: To test junior doctors' abilities to retain advanced life support psychomotor skills and theoretical knowledge in management of shockable rhythm cardiac arrest.

METHODS: A repeated measure pre-post study design was used with 43 junior doctors, recruited after notifying them with robust method of attraction through flyers, brochures, email and phone calls. Written and performance tests, initial pre-test, immediate post-training, 30-days post-training and 60-days post-training, using simulation-based scenarios with a low-fidelity manikin were used with recording performance of ALS.

INSTRUMENTATION: Resuscitation Council UK ALS algorithms and guidelines[1] were used in a simulated testing environment.

RESULTS: There was a highly significant improvement in knowledge immediately after training (p < 0.00), with a net gain of marks from a mean value of 63.2% before training to 87.7% after training by 24.5% (95% CI 19.4, 29.6).There was a gradual decline of retained knowledge with time from immediate post-training over, 30-days and 60-days post-training (p < 0.00). The simulation pre-training assessments and immediate post-training assessments results were statistically significant (p < .00). The mean difference was 44.1% (95% CI 50.11, 38.10). There was a statistically significant decline of the competency with time (p < .00). Unlike for the knowledge test, the drop was significant on the 30th day (p < .00) with a mean difference of -10.5% (95% CI -13.55, -7.40).

CONCLUSION: The training of junior doctors in shockable rhythm cardiac arrest in a low resource setting, improved knowledge and skills in the participants after training. However, retention of knowledge declined at 30 days and more significantly after 60 days and retention of skill was declined more significantly at 30 days.}, } @article {pmid37648703, year = {2023}, author = {Chan-Yao-Chong, M and Chan, J and Kono, H}, title = {Benchmarking of force fields to characterize the intrinsically disordered R2-FUS-LC region.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {14226}, pmid = {37648703}, issn = {2045-2322}, mesh = {Humans ; Amyotrophic Lateral Sclerosis ; *Intrinsically Disordered Proteins ; RNA-Binding Protein FUS ; Water ; }, abstract = {Intrinsically Disordered Proteins (IDPs) play crucial roles in numerous diseases like Alzheimer's and ALS by forming irreversible amyloid fibrils. The effectiveness of force fields (FFs) developed for globular proteins and their modified versions for IDPs varies depending on the specific protein. This study assesses 13 FFs, including AMBER and CHARMM, by simulating the R2 region of the FUS-LC domain (R2-FUS-LC region), an IDP implicated in ALS. Due to the flexibility of the region, we show that utilizing multiple measures, which evaluate the local and global conformations, and combining them together into a final score are important for a comprehensive evaluation of force fields. The results suggest c36m2021s3p with mTIP3p water model is the most balanced FF, capable of generating various conformations compatible with known ones. In addition, the mTIP3P water model is computationally more efficient than those of top-ranked AMBER FFs with four-site water models. The evaluation also reveals that AMBER FFs tend to generate more compact conformations compared to CHARMM FFs but also more non-native contacts. The top-ranking AMBER and CHARMM FFs can reproduce intra-peptide contacts but underperform for inter-peptide contacts, indicating there is room for improvement.}, } @article {pmid37648532, year = {2023}, author = {Kim, YS and Kim, YE and Choung, YH and Kim, H and Kim, HJ and Jung, NY and Lee, SM and Kim, EJ and Moon, SY}, title = {Pearls & Oy-sters: Familial Verbal Auditory Agnosia Due to C9orf72 Repeat Expansion.}, journal = {Neurology}, volume = {101}, number = {20}, pages = {e2046-e2050}, pmid = {37648532}, issn = {1526-632X}, mesh = {Humans ; Male ; Middle Aged ; *Frontotemporal Dementia/genetics ; *Amyotrophic Lateral Sclerosis/genetics/pathology ; C9orf72 Protein/genetics ; Proteins/genetics ; DNA Repeat Expansion/genetics ; *Pick Disease of the Brain/genetics ; }, abstract = {Chromosome 9 open reading frame 72 (C9orf72) gene pathogenic variants have been typically associated with frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS), but recent studies suggest their involvement in other disorders. This report describes a family with an autosomal dominant pattern of inheritance of progressive verbal auditory agnosia due to GGGGCC repeat expansion in C9orf72. A 60-year-old right-handed male truck driver presented with slowly progressive poor speech perception for 8 years, which became most troublesome when receiving verbal orders over the phone. He had difficulty recognizing single-syllable spoken words beyond his hearing loss but had no problem understanding complex written language. He had a heterozygous pathogenic variant carrying 160 hexanucleotide repeats in the C9orf72 gene. His family history included his deceased mother with similar symptoms that had progressed over 30 years, as well as his older brother and youngest sister who experienced speech perception difficulty beginning in their early fifties. His asymptomatic younger brother had a heterozygous 2 repeat in the C9orf72 gene, while his symptomatic youngest sister had a heterozygous 159 repeat. The patient and his sister exhibited more pronounced cortical thinning in the frontotemporoparietal areas. The discrepancy observed between the distribution of atrophy and the presentation of symptoms in patients with C9orf72 pathogenic repeat expansion may be attributable to the slow progression of their clinical course over time. The variable symptom presentation of C9orf72 pathogenic repeat expansion highlights the importance of considering this pathogenic variant as a potential cause of autosomal dominant degenerative brain diseases beyond FTD and ALS.}, } @article {pmid37648527, year = {2023}, author = {Kastner, S}, title = {A Marxist Exegesis of ALS.}, journal = {Neurology}, volume = {101}, number = {21}, pages = {966-967}, doi = {10.1212/WNL.0000000000207760}, pmid = {37648527}, issn = {1526-632X}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis ; }, } @article {pmid37647907, year = {2023}, author = {Gondim, FAA and Pinto, WBVR and Chieia, MAT and Correia, CDC and Cunha, FMB and Dourado, MET and França Júnior, MC and Marques Júnior, W and Oliveira, ASB and Rodrigues, CL and Silva, DJD and Dias-Tosta, E}, title = {Definitions, phenomenology, diagnosis, and management of the disorders of laughter and crying in amyotrophic lateral sclerosis (ALS): Consensus from ALS and Motor Neuron Disease Scientific Department of the Brazilian Academy of Neurology.}, journal = {Arquivos de neuro-psiquiatria}, volume = {81}, number = {8}, pages = {764-775}, pmid = {37647907}, issn = {1678-4227}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/therapy ; Brazil ; *Laughter ; Consensus ; Crying ; *Motor Neuron Disease ; *Neurology ; }, abstract = {The spectrum of neuropsychiatric phenomena observed in amyotrophic lateral sclerosis (ALS) is wide and not fully understood. Disorders of laughter and crying stand among the most common manifestations. The aim of this study is to report the results of an educational consensus organized by the Brazilian Academy of Neurology to evaluate the definitions, phenomenology, diagnosis, and management of the disorders of laughter and crying in ALS patients. Twelve members of the Brazilian Academy of Neurology - considered to be experts in the field - were recruited to answer 12 questions about the subject. After exchanging revisions, a first draft was prepared. A face-to-face meeting was held in Fortaleza, Brazil on 9.23.22 to discuss it. The revised version was subsequently emailed to all members of the ALS Scientific Department from the Brazilian Academy of Neurology and the final revised version submitted for publication. The prevalence of pseudobulbar affect/pathological laughter and crying (PBA/PLC) in ALS patients from 15 combined studies and 3906 patients was 27.4% (N = 1070), ranging from 11.4% to 71%. Bulbar onset is a risk factor but there are limited studies evaluating the differences in prevalence among the different motor neuron diseases subtypes, including patients with and without frontotemporal dementia. Antidepressants and a combination of dextromethorphan and quinidine (not available in Brazil) are possible therapeutic options. This group of panelists acknowledge the multiple gaps in the current literature and reinforces the need for further studies.}, } @article {pmid37647208, year = {2024}, author = {Vázquez-Costa, JF}, title = {Do we really need to calculate a minimal important difference for ALSFRS-R?: A letter in response to 'Clinically meaningful change: evaluation of the Rasch-built Overall Amyotrophic Lateral Sclerosis Disability Scale (ROADS) and the ALSFRS-R' published in Vol. 24(3-4), pp. 311-316.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {25}, number = {1-2}, pages = {214-215}, doi = {10.1080/21678421.2023.2248199}, pmid = {37647208}, issn = {2167-9223}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis ; Surveys and Questionnaires ; *Persons with Disabilities ; Disease Progression ; }, } @article {pmid37646130, year = {2023}, author = {Pattee, GL and Genge, A and Couratier, P and Lunetta, C and Sobue, G and Aoki, M and Yoshino, H and Jackson, CE and Wymer, J and Salah, A and Nelson, S}, title = {Oral Edaravone - Introducing a Flexible Treatment Option for Amyotrophic Lateral Sclerosis.}, journal = {Expert review of neurotherapeutics}, volume = {23}, number = {10}, pages = {859-866}, doi = {10.1080/14737175.2023.2251687}, pmid = {37646130}, issn = {1744-8360}, mesh = {Humans ; Edaravone/pharmacokinetics ; *Amyotrophic Lateral Sclerosis/drug therapy ; *Neurodegenerative Diseases/drug therapy ; Free Radical Scavengers/pharmacology ; Administration, Intravenous ; }, abstract = {INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a progressive and incurable neurodegenerative disease. While pharmacotherapy options remain limited, the Food and Drug Administration (FDA) approved intravenous (IV) and oral edaravone for the treatment of ALS in 2017 and 2022, respectively. With the addition of oral edaravone, patients with ALS may exclusively use oral medications.

AREAS COVERED: The authors performed a review of the published literature using the United States (US) National Library of Medicine's PubMed.gov resource to describe the pharmacokinetics, pharmacodynamics, safety, and efficacy of oral edaravone, as well as pertinent completed and ongoing clinical trials, including the oral edaravone clinical trial development program. The clinical profile of oral edaravone is also discussed.

EXPERT OPINION: Edaravone has been shown to slow the rate of motor function deterioration experienced by patients with ALS. As the oral formulation has been approved, patients with ALS may use it alone or in combination with other approved therapeutics. Additional clinical trials and real-world evidence are ongoing to gain further understanding of the clinical profile of oral edaravone.}, } @article {pmid37646115, year = {2023}, author = {Vu, L and Garcia-Mansfield, K and Pompeiano, A and An, J and David-Dirgo, V and Sharma, R and Venugopal, V and Halait, H and Marcucci, G and Kuo, YH and Uechi, L and Rockne, RC and Pirrotte, P and Bowser, R}, title = {Proteomics and mathematical modeling of longitudinal CSF differentiates fast versus slow ALS progression.}, journal = {Annals of clinical and translational neurology}, volume = {10}, number = {11}, pages = {2025-2042}, pmid = {37646115}, issn = {2328-9503}, support = {R56 NS061867/NS/NINDS NIH HHS/United States ; R01 NS061867/NS/NINDS NIH HHS/United States ; P30 CA033572/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis ; Proteome/metabolism ; Proteomics/methods ; Biomarkers/cerebrospinal fluid ; Disease Progression ; Retinol-Binding Proteins, Plasma ; }, abstract = {OBJECTIVE: Amyotrophic lateral sclerosis (ALS) is a heterogeneous disease with a complex etiology that lacks biomarkers predicting disease progression. The objective of this study was to use longitudinal cerebrospinal fluid (CSF) samples to identify biomarkers that distinguish fast progression (FP) from slow progression (SP) and assess their temporal response.

METHODS: We utilized mass spectrometry (MS)-based proteomics to identify candidate biomarkers using longitudinal CSF from a discovery cohort of SP and FP ALS patients. Immunoassays were used to quantify and validate levels of the top biomarkers. A state-transition mathematical model was created using the longitudinal MS data that also predicted FP versus SP.

RESULTS: We identified a total of 1148 proteins in the CSF of all ALS patients. Pathway analysis determined enrichment of pathways related to complement and coagulation cascades in FPs and synaptogenesis and glucose metabolism in SPs. Longitudinal analysis revealed a panel of 59 candidate markers that could segregate FP and SP ALS. Based on multivariate analysis, we identified three biomarkers (F12, RBP4, and SERPINA4) as top candidates that segregate ALS based on rate of disease progression. These proteins were validated in the discovery and a separate validation cohort. Our state-transition model determined that the overall variance of the proteome over time was predictive of the disease progression rate.

INTERPRETATION: We identified pathways and protein biomarkers that distinguish rate of ALS disease progression. A mathematical model of the CSF proteome determined that the change in entropy of the proteome over time was predictive of FP versus SP.}, } @article {pmid37645951, year = {2023}, author = {Bridges, LR}, title = {Replicating RNA as a component of scrapie fibrils.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {37645951}, issn = {2692-8205}, support = {P41 GM103311/GM/NIGMS NIH HHS/United States ; R01 GM129325/GM/NIGMS NIH HHS/United States ; }, abstract = {Recently, electron cryo-microscopy (cryo-EM) maps of fibrils from the brains of mice and hamsters with five infectious scrapie strains have been published[1-5] and deposited in the electron microscopy data bank (EMDB)[6]. This represents long-awaited near-atomic level structural evidence, widely expected to confirm the protein-only prion hypothesis[7,8]. Instead, the maps reveal a second component, other than protein. The aim of the present study was to identify the nature of this second component, in the published maps[1-5], using an in silico approach. Extra densities (EDs) containing this component were continuous, straight, axial, at right angles to protein rungs and within hydrogen-bonding distance of protein, consistent with a role as guide and support in fibril construction. EDs co-located with strips of basic residues, notably lysines, and formed a conspicuous cladding over parts of the N-terminal lobe of the protein. In one ED, there was evidence of a Y-shaped polymer forming two antiparallel chains, consistent with replicating RNA. Although the protein-only prion hypothesis[7] is still popular, convincing counter-evidence for an essential role of RNA as a cofactor has amassed in the last 20 years[8]. The present findings go beyond this in providing evidence for RNA as the genetic element of scrapie. To reflect the monotonous nature of the protein interface, it is suggested that the RNA may be a tandem repeat. This is against the protein-only prion hypothesis and in favour of a more orthodox agent, more akin to a virus. Fibrils from brains of patients with Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and other neurodegenerations also contain EDs[9] and may be of a similar aetiology.}, } @article {pmid37645251, year = {2023}, author = {Rojas, F and Aguilar, R and Almeida, S and Fritz, E and Corvalán, D and Ampuero, E and Abarzúa, S and Garcés, P and Amaro, A and Diaz, I and Arredondo, C and Cortes, N and Sanchez, M and Mercado, C and Varela-Nallar, L and Gao, FB and Montecino, M and van Zundert, B}, title = {Mature iPSC-derived astrocytes of an ALS/FTD patient carrying the TDP43[A90V] mutation display a mild reactive state and release polyP toxic to motoneurons.}, journal = {Frontiers in cell and developmental biology}, volume = {11}, number = {}, pages = {1226604}, pmid = {37645251}, issn = {2296-634X}, support = {R01 NS101986/NS/NINDS NIH HHS/United States ; R21 NS119952/NS/NINDS NIH HHS/United States ; R37 NS057553/NS/NINDS NIH HHS/United States ; RF1 NS101986/NS/NINDS NIH HHS/United States ; }, abstract = {Astrocytes play a critical role in the maintenance of a healthy central nervous system and astrocyte dysfunction has been implicated in various neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). There is compelling evidence that mouse and human ALS and ALS/FTD astrocytes can reduce the number of healthy wild-type motoneurons (MNs) in co-cultures or after treatment with astrocyte conditioned media (ACM), independently of their genotype. A growing number of studies have shown that soluble toxic factor(s) in the ACM cause non-cell autonomous MN death, including our recent identification of inorganic polyphosphate (polyP) that is excessively released from mouse primary astrocytes (SOD1, TARDBP, and C9ORF72) and human induced pluripotent stem cells (iPSC)-derived astrocytes (TARDBP) to kill MNs. However, others have reported that astrocytes carrying mutant TDP43 do not produce detectable MN toxicity. This controversy is likely to arise from the findings that human iPSC-derived astrocytes exhibit a rather immature and/or reactive phenotype in a number of studies. Here, we have succeeded in generating a highly homogenous population of functional quiescent mature astrocytes from control subject iPSCs. Using identical conditions, we also generated mature astrocytes from an ALS/FTD patient carrying the TDP43[A90V] mutation. These mutant TDP43 patient-derived astrocytes exhibit key pathological hallmarks, including enhanced cytoplasmic TDP-43 and polyP levels. Additionally, mutant TDP43 astrocytes displayed a mild reactive signature and an aberrant function as they were unable to promote synaptogenesis of hippocampal neurons. The polyP-dependent neurotoxic nature of the TDP43[A90V] mutation was further confirmed as neutralization of polyP in ACM derived from mutant TDP43 astrocytes prevented MN death. Our results establish that human astrocytes carrying the TDP43[A90V] mutation exhibit a cell-autonomous pathological signature, hence providing an experimental model to decipher the molecular mechanisms underlying the generation of the neurotoxic phenotype.}, } @article {pmid37645021, year = {2023}, author = {Littleton, SW and Laghi, F}, title = {Pearls and pitfalls of respiratory testing in a patient with amyotrophic lateral sclerosis and COPD.}, journal = {Breathe (Sheffield, England)}, volume = {19}, number = {2}, pages = {230043}, pmid = {37645021}, issn = {1810-6838}, abstract = {Interpretation of pulmonary function testing in patients with amyotrophic lateral sclerosis must account for coexisting lung diseases, when making patient care decisions. https://bit.ly/3Co2yR0.}, } @article {pmid37644984, year = {2023}, author = {Raghavendran, HRB and Kumaramanickavel, G and Iwata, T}, title = {Editorial: Personalized medicine-Where do we stand regarding bench to bedside translation?.}, journal = {Frontiers in medicine}, volume = {10}, number = {}, pages = {1243896}, pmid = {37644984}, issn = {2296-858X}, } @article {pmid37644868, year = {2023}, author = {Marton, S and Miquel, E and Acosta-Rodríguez, J and Fontenla, S and Libisch, G and Cassina, P}, title = {SOD1[G93A] Astrocyte-Derived Extracellular Vesicles Induce Motor Neuron Death by a miRNA-155-5p-Mediated Mechanism.}, journal = {ASN neuro}, volume = {15}, number = {}, pages = {17590914231197527}, pmid = {37644868}, issn = {1759-0914}, mesh = {Mice ; Animals ; Superoxide Dismutase-1/genetics/metabolism ; *Amyotrophic Lateral Sclerosis/genetics/metabolism ; Astrocytes/metabolism ; *Neurodegenerative Diseases/metabolism ; Mice, Transgenic ; Motor Neurons ; *MicroRNAs/genetics ; *Extracellular Vesicles/metabolism ; Disease Models, Animal ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by upper and lower motor neuron (MN) degeneration. Astrocytes surrounding MNs are known to modulate ALS progression. When cocultured with astrocytes overexpressing the ALS-linked mutant Cu/Zn superoxide dismutase (SOD1[G93A]) or when cultured with conditioned medium from SOD1[G93A] astrocytes, MN survival is reduced. The exact mechanism of this neurotoxic effect is unknown. Astrocytes secrete extracellular vesicles (EVs) that transport protein, mRNA, and microRNA species from one cell to another. The size and protein markers characteristic of exosomes were observed in the EVs obtained from cultured astrocytes, indicating their abundance in exosomes. Here, we analyzed the microRNA content of the exosomes derived from SOD1[G93A] astrocytes and evaluated their role in MN survival. Purified MNs exposed to SOD1[G93A] astrocyte-derived exosomes showed reduced survival and neurite length compared to those exposed to exosomes derived from non-transgenic (non-Tg) astrocytes. Analysis of the miRNA content of the exosomes revealed that miR-155-5p and miR-582-3p are differentially expressed in SOD1[G93A] exosomes compared with exosomes from non-Tg astrocytes. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicates that miR-155-5p and miR-582-3p predicted targets are enriched in the neurotrophin signaling pathway. Importantly, when levels of miR-155-5p were reduced by incubation with a specific antagomir, SOD1[G93A] exosomes did not affect MN survival or neurite length. These results demonstrate that SOD1[G93A]-derived exosomes are sufficient to induce MN death, and miRNA-155-5p contributes to this effect. miRNA-155-5p may offer a new therapeutic target to modulate disease progression in ALS.}, } @article {pmid37644692, year = {2023}, author = {Clark, RM and Clark, CM and Lewis, KEA and Dyer, MS and Chuckowree, JA and Hoyle, JA and Blizzard, CA and Dickson, TC}, title = {Intranasal neuropeptide Y1 receptor antagonism improves motor deficits in symptomatic SOD1 ALS mice.}, journal = {Annals of clinical and translational neurology}, volume = {10}, number = {11}, pages = {1985-1999}, pmid = {37644692}, issn = {2328-9503}, mesh = {Mice ; Humans ; Animals ; *Amyotrophic Lateral Sclerosis/genetics ; Superoxide Dismutase-1/genetics ; Motor Neurons ; Mice, Transgenic ; Superoxide Dismutase/genetics ; Peptides/pharmacology ; *Neuropeptides/metabolism ; }, abstract = {OBJECTIVE: Neuropeptide Y (NPY) is a 36 amino acid peptide widely considered to provide neuroprotection in a range of neurodegenerative diseases. In the fatal motor neuron disease amyotrophic lateral sclerosis (ALS), recent evidence supports a link between NPY and ALS disease processes. The goal of this study was to determine the therapeutic potential and role of NPY in ALS, harnessing the brain-targeted intranasal delivery of the peptide, previously utilised to correct motor and cognitive phenotypes in other neurological conditions.

METHODS: To confirm the association with clinical disease characteristics, NPY expression was quantified in post-mortem motor cortex tissue of ALS patients and age-matched controls. The effect of NPY on ALS cortical pathophysiology was investigated using slice electrophysiology and multi-electrode array recordings of SOD1[G93A] cortical cultures in vitro. The impact of NPY on ALS disease trajectory was investigated by treating SOD1[G93A] mice intranasally with NPY and selective NPY receptor agonists and antagonists from pre-symptomatic and symptomatic phases of disease.

RESULTS: In the human post-mortem ALS motor cortex, we observe a significant increase in NPY expression, which is not present in the somatosensory cortex. In vitro, we demonstrate that NPY can ameliorate ALS hyperexcitability, while brain-targeted nasal delivery of NPY and a selective NPY Y1 receptor antagonist modified survival and motor deficits specifically within the symptomatic phase of the disease in the ALS SOD1[G93A] mouse.

INTERPRETATION: Taken together, these findings highlight the capacity for non-invasive brain-targeted interventions in ALS and support antagonism of NPY Y1Rs as a novel strategy to improve ALS motor function.}, } @article {pmid37644512, year = {2023}, author = {Morón-Oset, J and Fischer, LKS and Jauré, N and Zhang, P and Jahn, AJ and Supèr, T and Pahl, A and Isaacs, AM and Grönke, S and Partridge, L}, title = {Repeat length of C9orf72-associated glycine-alanine polypeptides affects their toxicity.}, journal = {Acta neuropathologica communications}, volume = {11}, number = {1}, pages = {140}, pmid = {37644512}, issn = {2051-5960}, support = {/WT_/Wellcome Trust/United Kingdom ; P40 OD018537/OD/NIH HHS/United States ; WT098565/Z/12/Z/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Animals ; *Amyotrophic Lateral Sclerosis/genetics ; C9orf72 Protein/genetics ; *Frontotemporal Dementia ; Peptides ; Dipeptides/toxicity ; Insulin ; Alanine ; Drosophila ; }, abstract = {G4C2 hexanucleotide repeat expansions in a non-coding region of the C9orf72 gene are the most common cause of familial amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). G4C2 insertion length is variable, and patients can carry up to several thousand repeats. Dipeptide repeat proteins (DPRs) translated from G4C2 transcripts are thought to be a main driver of toxicity. Experiments in model organisms with relatively short DPRs have shown that arginine-rich DPRs are most toxic, while polyGlycine-Alanine (GA) DPRs cause only mild toxicity. However, GA is the most abundant DPR in patient brains, and experimental work in animals has generally relied on the use of low numbers of repeats, with DPRs often tagged for in vivo tracking. Whether repeat length or tagging affect the toxicity of GA has not been systematically assessed. Therefore, we generated Drosophila fly lines expressing GA100, GA200 or GA400 specifically in adult neurons. Consistent with previous studies, expression of GA100 and GA200 caused only mild toxicity. In contrast, neuronal expression of GA400 drastically reduced climbing ability and survival of flies, indicating that long GA DPRs can be highly toxic in vivo. This toxicity could be abolished by tagging GA400. Proteomics analysis of fly brains showed a repeat-length-dependent modulation of the brain proteome, with GA400 causing earlier and stronger changes than shorter GA proteins. PolyGA expression up-regulated proteins involved in ER to Golgi trafficking, and down-regulated proteins involved in insulin signalling. Experimental down-regulation of Tango1, a highly conserved regulator of ER-to Golgi transport, partially rescued GA400 toxicity, suggesting that misregulation of this process contributes to polyGA toxicity. Experimentally increasing insulin signaling also rescued GA toxicity. In summary, our data show that long polyGA proteins can be highly toxic in vivo, and that they may therefore contribute to ALS/FTD pathogenesis in patients.}, } @article {pmid37642362, year = {2023}, author = {Bireley, JD and Morren, JA}, title = {CNM-Au8: an experimental agent for the treatment of amyotrophic lateral sclerosis (ALS).}, journal = {Expert opinion on investigational drugs}, volume = {32}, number = {8}, pages = {677-683}, doi = {10.1080/13543784.2023.2252738}, pmid = {37642362}, issn = {1744-7658}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy ; Edaravone/pharmacokinetics/therapeutic use ; *Neuroprotective Agents/pharmacology/therapeutic use ; Quality of Life ; Drugs, Investigational/therapeutic use ; }, abstract = {INTRODUCTION: Two established disease-specific therapies for the treatment of amyotrophic lateral sclerosis (ALS) are riluzole and edaravone. Limitations of these medications include minimal progression slowing or survival benefit, and effectiveness only in selected populations, particularly for edaravone. AMX0035 and tofersen received US FDA approval in September 2022 and April 2023, respectively. However, phase 3 trials, further examining both medications' efficacy, are ongoing. CNM-Au8 is an efficient catalyst of energy metabolism and is therefore a potential disease-modifying treatment for ALS, a neurodegenerative condition in which there is bioenergetics impairment.

AREAS COVERED: In this review, we provide an overview of the current ALS treatment market, followed by a description of the pharmacodynamics and pharmacokinetics of CNM-Au8. The main preclinical and available early clinical evidence of CNM-Au8 is then described, as well as its potential as an ALS treatment.

EXPERT OPINION: Oral treatment with CNM-Au8 failed to meet primary clinical and electrodiagnostic endpoints in phase 2/3 clinical trials. Despite this failure, a number of exploratory endpoints included in phase 2/3 trials suggest CNM-Au8 has the potential to significantly slow clinical worsening, improve quality of life, and prolong survival in ALS. Further study of CNM-Au8 in a phase 3 clinical trial is currently underway.}, } @article {pmid37642179, year = {2023}, author = {Tucker, H and Duncan, T and Craven, PA and Goode, C and Scheidler, J}, title = {A Retrospective Application of the Arbon and Hartman Models to the Union Cycliste International Mountain Bike World Cup.}, journal = {Prehospital and disaster medicine}, volume = {38}, number = {5}, pages = {612-616}, pmid = {37642179}, issn = {1945-1938}, mesh = {Humans ; *Emergency Medical Services/methods ; Retrospective Studies ; Bicycling ; Mass Behavior ; Mass Gatherings ; }, abstract = {INTRODUCTION: Outdoor activities have accelerated in the past several years. The authors were tasked with providing medical care for the Union Cycliste International (UCI) mountain biking World Cup in Snowshoe, West Virginia (USA) in September 2021. The Hartman and Arbon models were designed to predict patient presentation and hospital transport rates as well as needed medical resources at urban mass-gathering events. However, there is a lack of standardized methods to predict injury, illness, and insult severity at rural mass gatherings.

STUDY OBJECTIVE: This study aimed to determine whether the Arbon model would predict, within 10%, the number of patient presentations to be expected and to determine if the event classification provided by the Hartman model would adequately predict resources needed during the event.

METHODS: Race data were collected from UCI event officials and injury data were collected from participants at time of presentation for medical care. Predicted presentation and transport rates were calculated using the Arbon model, which was then compared to the actual observed presentation rates. Furthermore, the event classification provided by the Hartman model was compared to the resources utilized during the event.

RESULTS: During the event, 34 patients presented for medical care and eight patients required some level of transport to a medical facility. The Arbon predictive model for the 2021 event yielded 30.3 expected patient presentations. There were 34 total patient presentations during the 2021 race, approximately 11% more than predicted. The Hartman model yielded a score of four. Based on this score, this race would be classified as an "intermediate" event, requiring multiple Advanced Life Support (ALS) and Basic Life Support (BLS) personnel and transport units.

CONCLUSION: The Arbon model provided a predicted patient presentation rate within reasonable error to allow for effective pre-event planning and resource allocation with only a four patient presentation difference from the actual data. While the Arbon model under-predicted patient presentations, the Hartman model under-estimated resources needed due to the high-risk nature of downhill cycling. The events staffed required physician skills and air medical services to safely care for patients. Further evaluation of rural events will be needed to determine if there is a generalized need for physician presence at smaller events with inherently risky activities, or if this recurring cycling event is an outlier.}, } @article {pmid37642165, year = {2023}, author = {Shelash Al-Hawary, SI and Yahya Ali, A and Mustafa, YF and Margiana, R and Maksuda Ilyasovna, S and Ramadan, MF and Almalki, SG and Alwave, M and Alkhayyat, S and Alsalamy, A}, title = {The microRNAs (miRs) overexpressing mesenchymal stem cells (MSCs) therapy in neurological disorders; hope or hype.}, journal = {Biotechnology progress}, volume = {39}, number = {6}, pages = {e3383}, doi = {10.1002/btpr.3383}, pmid = {37642165}, issn = {1520-6033}, mesh = {Humans ; *MicroRNAs/genetics/metabolism ; *Nervous System Diseases/genetics/therapy/metabolism ; *Mesenchymal Stem Cells/metabolism ; *Parkinson Disease/therapy ; Neurogenesis ; }, abstract = {Altered expression of multiple miRNAs was found to be extensively involved in the pathogenesis of different neurological disorders including Alzheimer's disease, Parkinson's disease, stroke, epilepsy, multiple sclerosis, amyotrophic lateral sclerosis, and Huntington's disease. One of the biggest concerns within gene-based therapy is the delivery of the therapeutic microRNAs to the intended place, which is obligated to surpass the biological barriers without undergoing degradation in the bloodstream or renal excretion. Hence, the delivery of modified and unmodified miRNA molecules using excellent vehicles is required. In this light, mesenchymal stem cells (MSCs) have attracted increasing attention. The MSCs can be genetically modified to express or overexpress a particular microRNA aimed with promote neurogenesis and neuroprotection. The current review has focused on the therapeutic capabilities of microRNAs-overexpressing MSCs to ameliorate functional deficits in neurological conditions.}, } @article {pmid37641631, year = {2023}, author = {Fetit, R}, title = {Celebrating the life and research of BNA Past-President Colin Blakemore.}, journal = {Brain and neuroscience advances}, volume = {7}, number = {}, pages = {23982128231195514}, pmid = {37641631}, issn = {2398-2128}, abstract = {Professor Sir Colin Blakemore was a remarkable neuroscientist, persuasive communicator, and brave advocate for animal research who, sadly, passed away in June 2022 from amyotrophic lateral sclerosis. His work helped establish the concept of neuronal plasticity, which was fundamental to our understanding of the postnatal brain and continues to impact our outlook on neurodegenerative disorders. The BNA2023 Festival of Neuroscience dedicated its last plenary session in his honour, bringing together five prominent neuroscientists whose careers were shaped by Professor Blakemore. Here, we summarise the speakers' reflections on how Colin's support, generosity, and foresight influenced their academic paths, inspired their research, and changed their outlook on life.}, } @article {pmid37641579, year = {2024}, author = {Shefner, JM and Jacobsen, B and Kupfer, S and Malik, FI and Meng, L and Wei, J and Wolff, AA and Rudnicki, SA}, title = {Relationship between quantitative strength and functional outcomes in the phase 2 FORTITUDE-ALS trial.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {25}, number = {1-2}, pages = {162-169}, doi = {10.1080/21678421.2023.2252468}, pmid = {37641579}, issn = {2167-9223}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/drug therapy ; Hand Strength ; Quality of Life ; Surveys and Questionnaires ; Muscle Strength ; Disease Progression ; }, abstract = {OBJECTIVE: To assess the relationship among measurements of strength, function, and quality of life in an amyotrophic lateral sclerosis (ALS) clinical trial.

METHODS: In the FORTITUDE-ALS clinical trial (NCT03160898), 456 participants in the full-analysis set were treated with either reldesemtiv or placebo for 12 weeks; this post hoc analysis included all participants regardless of treatment assignments. Assessments included slow vital capacity (SVC), the ALS Functional Rating Scale-Revised (ALSFRS-R), and the 5-item ALS Assessment Questionnaire (ALSAQ-5). Muscle strength was measured quantitatively with hand-held dynamometry, and grip strength with a dedicated dynamometer. The relationship between strength and ALSFRS-R fine and gross motor domain scores, or responses to ALSAQ-5 questions on hand function and walking, was assessed with Spearman's rank correlation. The relationship between mean upper- or lower-extremity muscle strength and specific ALSFRS-R domains was modeled using principal-components analysis.

RESULTS: Upper-extremity muscle strength and hand grip were highly correlated with ALSFRS-R fine motor scores and the ALSAQ-5 hand function question. Similarly, lower-extremity strength correlated well with ALSFRS-R gross motor domain and the ALSAQ-5 walking question. For SVC, correlation was poor with the ALSFRS-R respiratory domain, but stronger with the total score, potentially reflecting the insensitivity of the respiratory questions in the scale. Upper- and lower-extremity strength were both strong predictors of ALSFRS-R domain scores.

CONCLUSIONS: In this analysis of data from an ALS clinical trial, muscle strength quantified by dynamometry was strongly correlated with functional capacity. These results suggest that muscle strength directly relates to specific functions of importance to people with ALS.}, } @article {pmid37641443, year = {2023}, author = {Maragakis, NJ and de Carvalho, M and Weiss, MD}, title = {Therapeutic targeting of ALS pathways: Refocusing an incomplete picture.}, journal = {Annals of clinical and translational neurology}, volume = {10}, number = {11}, pages = {1948-1971}, pmid = {37641443}, issn = {2328-9503}, support = {R01 NS117604/NS/NINDS NIH HHS/United States ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/pathology ; *Neurodegenerative Diseases ; Biomarkers ; }, abstract = {Numerous potential amyotrophic lateral sclerosis (ALS)-relevant pathways have been hypothesized and studied preclinically, with subsequent translation to clinical trial. However, few successes have been observed with only modest effects. Along with an improved but incomplete understanding of ALS as a neurodegenerative disease is the evolution of more sophisticated and diverse in vitro and in vivo preclinical modeling platforms, as well as clinical trial designs. We highlight proposed pathological pathways that have been major therapeutic targets for investigational compounds. It is likely that the failures of so many of these therapeutic compounds may not have occurred because of lack of efficacy but rather because of a lack of preclinical modeling that would help define an appropriate disease pathway, as well as a failure to establish target engagement. These challenges are compounded by shortcomings in clinical trial design, including lack of biomarkers that could predict clinical success and studies that are underpowered. Although research investments have provided abundant insights into new ALS-relevant pathways, most have not yet been developed more fully to result in clinical study. In this review, we detail some of the important, well-established pathways, the therapeutics targeting them, and the subsequent clinical design. With an understanding of some of the shortcomings in translational efforts over the last three decades of ALS investigation, we propose that scientists and clinicians may choose to revisit some of these therapeutic pathways reviewed here with an eye toward improving preclinical modeling, biomarker development, and the investment in more sophisticated clinical trial designs.}, } @article {pmid37640472, year = {2023}, author = {Yamamuro-Tanabe, A and Kosuge, Y and Ishimaru, Y and Yoshioka, Y}, title = {Schwann cell derived-peroxiredoxin protects motor neurons against hydrogen peroxide-induced cell death in mouse motor neuron cell line NSC-34.}, journal = {Journal of pharmacological sciences}, volume = {153}, number = {2}, pages = {73-83}, doi = {10.1016/j.jphs.2023.07.006}, pmid = {37640472}, issn = {1347-8648}, mesh = {Animals ; Mice ; *Hydrogen Peroxide/toxicity ; *Amyotrophic Lateral Sclerosis/genetics ; Reactive Oxygen Species ; Superoxide Dismutase-1/genetics ; Motor Neurons ; Cell Death ; Schwann Cells ; Cell Line ; Peroxiredoxins/genetics ; }, abstract = {Schwann cells and oligodendrocytes secrete proteins that promote neuron survival, but their role in amyotrophic lateral sclerosis (ALS) is unclear. To address this question, we evaluated the effect of molecules secreted by Schwann cells on reactive oxygen species (ROS)-induced motor neuronal cell death. We observed that in motor neuron cell line NSC-34 cultures, the conditioned medium (CM) from Schwann cell line YST-1 (YST-1 CM) cultures had a protective effect against hydrogen peroxide-induced cell death. However, this protective effect of YST-1 CM was abolished by removing peroxiredoxin 1-4 (PRDX1-4) from the CM. We found that the expression of PRDX1 mRNA was markedly downregulated in the lumbar spinal cord of the superoxide dismutase 1 (SOD1)[G93A] mouse model of ALS. We also found that transient transfection of YST-1 cells with G93A SOD1 resulted in reduced PRDX1 mRNA expression. Additionally, in the mutant transfected cells, YST-1 CM showed decreased neuroprotective effect against hydrogen peroxide-induced NSC-34 cell death compared to those transfected with WT SOD1. Our results suggest that Schwann cells protect motor neurons from oxidative stress by secreting PRDX1 and that the reduction of PRDX secreted from Schwann cells contributes to increased ROS and associated motor neuronal death in ALS.}, } @article {pmid37640438, year = {2023}, author = {Hong Tuan Ha, V and Jost, D and Bougouin, W and Joly, G and Jouffroy, R and Jabre, P and Beganton, F and Derkenne, C and Lemoine, S and Frédéric, L and Lamhaut, L and Loeb, T and Revaux, F and Dumas, F and Trichereau, J and Stibbe, O and Deye, N and Marijon, E and Cariou, A and Jouven, X and Travers, S}, title = {Trends in survival from out-of-hospital cardiac arrest with a shockable rhythm and its association with bystander resuscitation: a retrospective study.}, journal = {Emergency medicine journal : EMJ}, volume = {40}, number = {11}, pages = {761-767}, doi = {10.1136/emermed-2023-213220}, pmid = {37640438}, issn = {1472-0213}, mesh = {Humans ; *Cardiopulmonary Resuscitation ; Retrospective Studies ; *Out-of-Hospital Cardiac Arrest ; Defibrillators ; Arrhythmias, Cardiac ; *Emergency Medical Services ; }, abstract = {OBJECTIVE: Over 300 000 cases of out-of-hospital cardiac arrests (OHCAs) occur each year in the USA and Europe. Despite decades of investment and research, survival remains disappointingly low. We report the trends in survival after a ventricular fibrillation/pulseless ventricular tachycardia OHCA, over a 13-year period, in a French urban region, and describe the simultaneous evolution of the rescue system.

METHODS: We investigated four 18-month periods between 2005 and 2018. The first period was considered baseline and included patients from the randomised controlled trial 'DEFI 2005'. The three following periods were based on the Paris Sudden Death Expertise Center Registry (France). Inclusion criteria were non-traumatic cardiac arrests treated with at least one external electric shock with an automated external defibrillator from the basic life support team and resuscitated by a physician-staffed ALS team. Primary outcome was survival at hospital discharge with a good neurological outcome.

RESULTS: Of 21 781 patients under consideration, 3476 (16%) met the inclusion criteria. Over all study periods, survival at hospital discharge increased from 12% in 2005 to 25% in 2018 (p<0.001), and return of spontaneous circulation at hospital admission increased from 43% to 58% (p=0.004).Lay-rescuer cardiopulmonary resuscitation (CPR) and telephone CPR (T-CPR) rates increased significantly, but public defibrillator use remained limited.

CONCLUSION: In a two-tiered rescue system, survival from OHCA at hospital discharge doubled over a 13-year study period. Concomitantly, the system implemented an OHCA patient registry and increased T-CPR frequency, despite a consistently low rate of public defibrillator use.}, } @article {pmid37639764, year = {2023}, author = {Stenson, K and O'Callaghan, L and Mellor, J and Wright, J and Gibson, G and Earl, L and Barlow, S and Fournier, CN}, title = {Healthcare resource utilization at different stages of amyotrophic lateral sclerosis: Results from a real-world survey.}, journal = {Journal of the neurological sciences}, volume = {452}, number = {}, pages = {120764}, doi = {10.1016/j.jns.2023.120764}, pmid = {37639764}, issn = {1878-5883}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/epidemiology/therapy ; Patient Acceptance of Health Care ; France ; *General Practitioners ; Germany ; }, abstract = {People with amyotrophic lateral sclerosis (pALS) require complex, multi-disciplinary care, resulting in extensive healthcare resource utilization (HCRU). To investigate the relationship between HCRU and ALS progression, the study objectives were (i) to characterize HCRU in pALS and (ii) to establish whether this varied according to disease stage, as defined using three different methodologies: neurologist-defined early/mid/late stage, the King's clinical staging system for ALS, and the Milan Torino Staging system for ALS (MiToS). Real-world data were drawn from the Adelphi ALS Disease-Specific Programme™, a point-in-time survey of neurologists in France, Germany, Italy, Spain, the UK, and the USA conducted July 2020-March 2021. The analysis included survey responses from 142 physicians with respect to 880 pALS. With advancing ALS stage, significant differences were observed in the number of healthcare professional consultations and X-rays per person (both p < 0.05 for all staging systems), and the proportion of pALS with emergency room admissions, intensive care unit admissions, and assisted ventilation (all p < 0.05 for all staging systems). Across stages, >55% of pALS received care from a general neurologist and a general/primary care practitioner. With increasing stage, there was a significant difference in the proportion receiving care from a physical therapist, pulmonologist/respiratory care practitioner, respiratory therapist, speech/language therapist, and palliative care team, and in the proportion receiving care only from professional caregivers (all p < 0.05 for all staging systems). This study confirmed the substantial HCRU required to support pALS through all stages of ALS and highlighted an increasing need for healthcare resources as the disease progresses.}, } @article {pmid37639327, year = {2024}, author = {Baskerville, V and Rapuri, S and Mehlhop, E and Coyne, AN}, title = {SUN1 facilitates CHMP7 nuclear influx and injury cascades in sporadic amyotrophic lateral sclerosis.}, journal = {Brain : a journal of neurology}, volume = {147}, number = {1}, pages = {109-121}, pmid = {37639327}, issn = {1460-2156}, support = {R00 NS123242/NS/NINDS NIH HHS/United States ; R01 NS132836/NS/NINDS NIH HHS/United States ; R00NS123242/GF/NIH HHS/United States ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism ; *Frontotemporal Dementia/pathology ; *Pick Disease of the Brain ; C9orf72 Protein/genetics/metabolism ; Neurons/metabolism ; Membrane Proteins ; Microtubule-Associated Proteins ; Nuclear Proteins ; Endosomal Sorting Complexes Required for Transport ; }, abstract = {We have recently identified the aberrant nuclear accumulation of the ESCRT-III protein CHMP7 as an initiating event that leads to a significant injury to the nuclear pore complex (NPC) characterized by the reduction of specific nucleoporins from the neuronal NPC in sporadic amyotrophic lateral sclerosis (sALS) and C9orf72 ALS/frontotemporal dementia (FTD)-induced pluripotent stem cell-derived neurons (iPSNs), a phenomenon also observed in post-mortem patient tissues. Importantly, this NPC injury is sufficient to contribute to TDP-43 dysfunction and mislocalization, a common pathological hallmark of neurodegenerative diseases. However, the molecular mechanisms and events that give rise to increased nuclear translocation and/or retention of CHMP7 to initiate this pathophysiological cascade remain largely unknown. Here, using an iPSN model of sALS, we demonstrate that impaired NPC permeability barrier integrity and interactions with the LINC complex protein SUN1 facilitate CHMP7 nuclear localization and the subsequent 'activation' of NPC injury cascades. Collectively, our data provide mechanistic insights in the pathophysiological underpinnings of ALS/FTD and highlight SUN1 as a potent contributor to and modifier of CHMP7-mediated toxicity in sALS pathogenesis.}, } @article {pmid37639066, year = {2024}, author = {Ma, Y and Jia, T and Qin, F and He, Y and Han, F and Zhang, C}, title = {Abnormal Brain Protein Abundance and Cross-tissue mRNA Expression in Amyotrophic Lateral Sclerosis.}, journal = {Molecular neurobiology}, volume = {61}, number = {1}, pages = {510-518}, pmid = {37639066}, issn = {1559-1182}, support = {2021YFS0248//Key R & D Projects of Science and Technology Department of Sichuan Province/ ; 2020HXBH163//Postdoctoral Foundation of West China Hospital/ ; 20221174L//College Students' innovation and entrepreneurship training program/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism ; Genome-Wide Association Study ; Bayes Theorem ; Brain/metabolism ; Proteome/metabolism ; RNA, Messenger/genetics ; ATPases Associated with Diverse Cellular Activities/genetics/metabolism ; Electron Transport Complex III/metabolism ; 17-Hydroxysteroid Dehydrogenases/metabolism ; }, abstract = {Due to the limitations of the present risk genes in understanding the etiology of amyotrophic lateral sclerosis (ALS), it is necessary to find additional causative genes utilizing novel approaches. In this study, we conducted a two-stage proteome-wide association study (PWAS) using ALS genome-wide association study (GWAS) data (N = 152,268) and two distinct human brain protein quantitative trait loci (pQTL) datasets (ROSMAP N = 376 and Banner N = 152) to identify ALS risk genes and prioritized candidate genes with Mendelian randomization (MR) and Bayesian colocalization analysis. Next, we verified the aberrant expression of risk genes in multiple tissues, including lower motor neurons, skeletal muscle, and whole blood. Six ALS risk genes (SCFD1, SARM1, TMEM175, BCS1L, WIPI2, and DHRS11) were found during the PWAS discovery phase, and SARM1 and BCS1L were confirmed during the validation phase. The following MR (p = 2.10 × 10[-7]) and Bayesian colocalization analysis (ROSMAP PP4 = 0.999, Banner PP4 = 0.999) confirmed the causal association between SARM1 and ALS. Further differential expression analysis revealed that SARM1 was markedly downregulated in lower motor neurons (p = 7.64 × 10[-3]), skeletal muscle (p = 9.34 × 10[-3]), and whole blood (p = 1.94 × 10[-3]). Our findings identified some promising protein candidates for future investigation as therapeutic targets. The dysregulation of SARM1 in multiple tissues provides a new way to explain ALS pathology.}, } @article {pmid37638500, year = {2024}, author = {Ross, JP and Akçimen, F and Liao, C and Kwan, K and Phillips, DE and Schmilovich, Z and Spiegelman, D and Genge, A and Dupré, N and Dion, PA and Farhan, SMK and Rouleau, GA}, title = {Rare-variant and polygenic analyses of amyotrophic lateral sclerosis in the French-Canadian genome.}, journal = {Genetics in medicine : official journal of the American College of Medical Genetics}, volume = {26}, number = {1}, pages = {100967}, doi = {10.1016/j.gim.2023.100967}, pmid = {37638500}, issn = {1530-0366}, mesh = {Humans ; Genetic Association Studies ; *Amyotrophic Lateral Sclerosis/epidemiology/genetics ; Genome-Wide Association Study ; Canada ; Genome ; Genetic Predisposition to Disease ; }, abstract = {PURPOSE: The genetic etiology of amyotrophic lateral sclerosis (ALS) includes few rare, large-effect variants and potentially many common, small-effect variants per case. The genetic risk liability for ALS might require a threshold comprised of a certain amount of variants. Here, we tested the degree to which risk for ALS was affected by rare variants in ALS genes, polygenic risk score, or both.

METHODS: 335 ALS cases and 356 controls from Québec, Canada were concurrently tested by microarray genotyping and targeted sequencing of ALS genes known at the time of study inception. ALS genome-wide association studies summary statistics were used to estimate an ALS polygenic risk score (PRS). Cases and controls were subdivided into rare-variant heterozygotes and non-heterozygotes.

RESULTS: Risk for ALS was significantly associated with PRS and rare variants independently in a logistic regression model. Although ALS PRS predicted a small amount of ALS risk overall, the effect was most pronounced between ALS cases and controls that were not heterozygous for a rare variant in the ALS genes surveyed.

CONCLUSION: Both PRS and rare variants in ALS genes impact risk for ALS. PRS for ALS is most informative when rare variants are not observed in ALS genes.}, } @article {pmid37638449, year = {2023}, author = {McCann, EP and Grima, N and Fifita, JA and Chan Moi Fat, S and Lehnert, K and Henden, L and Blair, IP and Williams, KL}, title = {Characterising the Genetic Landscape of Amyotrophic Lateral Sclerosis: A Catalogue and Assessment of Over 1,000 Published Genetic Variants.}, journal = {Journal of neuromuscular diseases}, volume = {10}, number = {6}, pages = {1127-1141}, pmid = {37638449}, issn = {2214-3602}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics ; *Neurodegenerative Diseases ; Gene Frequency ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with genetic and phenotypic heterogeneity. Pathogenic genetic variants remain the only validated cause of disease, the majority of which were discovered in familial ALS patients. While causal gene variants are a lesser contributor to sporadic ALS, an increasing number of risk alleles (low penetrance genetic variants associated with a small increase in disease risk) and variants of uncertain significance have been reported.

OBJECTIVE: To examine the pathogenic potential of genetic variation in ALS, we sought to characterise variant- and gene-level attributes of previously reported ALS-implicated variants.

METHODS: A list of 1,087 genetic variants reported in ALS to March 2021 was compiled through comprehensive literature review. Individual variants were annotated using in silico tools and databases across variant features including pathogenicity scores, localisation to protein domains, evolutionary conservation, and minor allele frequencies. Gene level attributes of genic tolerance, gene expression in ALS-relevant tissues and gene ontology terms were assessed for 33 ALS genes. Statistical analysis was performed for each characteristic, and we compared the most penetrant variants found in familial cases with risk alleles exclusive to sporadic cases, to explore genetic variant features that associate with disease penetrance.

RESULTS: We provide spreadsheet (hg19 and GRCh38) and variant call format (GRCh38) resources for all 1,087 reported ALS-implicated variants, including detailed summaries for each attribute. We demonstrate that the characteristics of variants found exclusively in sporadic ALS cases are less severe than those observed in familial ALS.

CONCLUSIONS: We provide a comprehensive, literature-derived catalogue of genetic variation in ALS thus far and reveal crucial attributes that contribute to ALS pathogenicity. Our variant- and gene-level observations highlight the complexity of genetic variation in ALS, and we discuss important implications and considerations for novel variant interpretation.}, } @article {pmid37638324, year = {2023}, author = {Zhou, W and Xu, R}, title = {Current insights in the molecular genetic pathogenesis of amyotrophic lateral sclerosis.}, journal = {Frontiers in neuroscience}, volume = {17}, number = {}, pages = {1189470}, pmid = {37638324}, issn = {1662-4548}, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neurodegenerative disease that leads to the massive loss of motor neurons in cerebrum, brain stem and spinal cord. It affects not only motor neurons but also other neurons and glial cells, resulting in the progressive muscle atrophy, the severe disability and the eventual death due to the respiratory failure. The pathogenesis of ALS is not fully understood. Currently, several factors are considered to be involved in the pathogenesis of ALS, such as genetic factors, imbalances in protein homeostasis, RNA metabolism disorders, mitochondrial dysfunctions, glutamate-mediated excitatory toxicities and intra-neuronal material transport disorders in neurons. The study of genetic mutations related to ALS pathogenesis will link the molecular and cellular mechanisms of the disease, thus enhancing the understanding of its occurrence and progression, thereby providing new insights for the pathogenesis of ALS. This review summarizes the current insights in the molecular genetic pathogenesis of ALS.}, } @article {pmid37636591, year = {2023}, author = {Jamali, AM and Kethamreddy, M and Burkett, BJ and Port, JD and Pandey, MK}, title = {PET and SPECT Imaging of ALS: An Educational Review.}, journal = {Molecular imaging}, volume = {2023}, number = {}, pages = {5864391}, pmid = {37636591}, issn = {1536-0121}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnostic imaging ; Positron-Emission Tomography ; Tomography, Emission-Computed, Single-Photon ; Brain/diagnostic imaging ; Fluorodeoxyglucose F18 ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a disease leading to progressive motor degeneration and ultimately death. It is a complex disease that can take a significantly long time to be diagnosed, as other similar pathological conditions must be ruled out for a definite diagnosis of ALS. Noninvasive imaging of ALS has shed light on disease pathology and altered biochemistry in the ALS brain. Other than magnetic resonance imaging (MRI), two types of functional imaging, positron emission tomography (PET) and single photon emission computed tomography (SPECT), have provided valuable data about what happens in the brain of ALS patients compared to healthy controls. PET imaging has revealed a specific pattern of brain metabolism through [[18]F]FDG, while other radiotracers have uncovered neuroinflammation, changes in neuronal density, and protein aggregation. SPECT imaging has shown a general decrease in regional cerebral blood flow (rCBF) in ALS patients. This educational review summarizes the current state of ALS imaging with various PET and SPECT radiopharmaceuticals to better understand the pathophysiology of ALS.}, } @article {pmid37636024, year = {2023}, author = {Nouri Nojadeh, J and Bildiren Eryilmaz, NS and Ergüder, BI}, title = {CRISPR/Cas9 genome editing for neurodegenerative diseases.}, journal = {EXCLI journal}, volume = {22}, number = {}, pages = {567-582}, pmid = {37636024}, issn = {1611-2156}, abstract = {Gene therapy has emerged as a promising therapeutic strategy for various conditions, including blood disorders, ocular disease, cancer, and nervous system disorders. The advent of gene editing techniques has facilitated the ability of researchers to specifically target and modify the eukaryotic cell genome, making it a valuable tool for gene therapy. This can be performed through either in vivo or ex vivo approaches. Gene editing tools, such as zinc finger nucleases, transcription activator-like effector nucleases, and CRISPR-Cas-associated nucleases, can be employed for gene therapy purposes. Among these tools, CRISPR-Cas-based gene editing stands out because of its ability to introduce heritable genome changes by designing short guide RNAs. This review aims to provide an overview of CRISPR-Cas technology and summarizes the latest research on the application of CRISPR/Cas9 genome editing technology for the treatment of the most prevalent neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, Huntington's disease, Amyotrophic lateral sclerosis, and Spinocerebellar ataxia.}, } @article {pmid37635943, year = {2023}, author = {Alshafie, W and Fotouhi, M and Ayoubi, R and Shlaifer, I and Southern, K and McPherson, PS and Laflamme, C and , }, title = {The identification of high-performing antibodies for Charged multivesicular body protein 2b for use in Western Blot, immunoprecipitation and immunofluorescence.}, journal = {F1000Research}, volume = {12}, number = {}, pages = {884}, pmid = {37635943}, issn = {2046-1402}, support = {SGC/JAN18/988-797/MNDA_/Motor Neurone Disease Association/United Kingdom ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis ; *Frontotemporal Dementia ; Multivesicular Bodies ; Reproducibility of Results ; Blotting, Western ; Fluorescent Antibody Technique ; Immunoprecipitation ; Antibodies ; }, abstract = {Charged multivesicular body protein 2B is a subunit of the endosomal sorting complex required for transport III (ESRCT-III), a complex implicated in the lysosomal degradation pathway and formation of multivesicular bodies. Mutations to the CHMP2B gene can result in abnormal protein aggregates in neurons and is therefore predicted to be associated in neurodegenerative diseases, including across the ALS-FTD spectrum. Through our standardized experimental protocol which compares read-outs in knockout cell lines and isogenic parental controls, this study aims to enhance the reproducibility of research on this target by characterizing eight commercial antibodies against charged multivesicular body protein 2b using Western Blot, immunoprecipitation, and immunofluorescence. We identified many high-performing antibodies and encourage readers to use this report as a guide to select the most appropriate antibody for their specific needs.}, } @article {pmid37635508, year = {2023}, author = {Djordjevic, G and Milosevic, V and Ljubisavljevic, S and Stojanovic, I and Stojanov, A}, title = {Values of Nitric Oxide and Superoxide Dismutase in Cerebrospinal Fluid of Patients with Sporadic Amyotrophic Lateral Sclerosis.}, journal = {Neurology India}, volume = {71}, number = {4}, pages = {742-747}, doi = {10.4103/0028-3886.383853}, pmid = {37635508}, issn = {1998-4022}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis ; Nitric Oxide/cerebrospinal fluid ; Superoxide Dismutase/cerebrospinal fluid ; Disease Progression ; }, abstract = {INTRODUCTION: Neurons are highly energy-dependent and highly specialized cells, showing great sensitivity to oxidative stress (OS). Nitric oxide (NO) and its oxidation products play a central role in neurodegeneration. This study aimed to contribute to the further elucidation of the role of OS in the pathogenesis of amyotrophic lateral sclerosis (ALS).

METHODS: We assessed NO and superoxide dismutase (SOD) levels in cerebrospinal fluid (CSF) of 24 sporadic ALS (sALS) patients (13 of them presented with spinal form while 11 patients had bulbar form) and 20 controls (CG).

RESULTS: The obtained SOD levels in sALS patients were lower than those in CG (p < 0.001), while NO showed higher levels compared to CG (p < 0.001). Observed separately, there were no significant differences in the levels of NO and SOD in CSF between patients about their clinical presentations (p > 0.05). There were significant negative correlations between SOD and NO levels in all sALS patients (r = 0.31, P = 0.025). Significant correlation between SOD and functional rating scale as well as disease progression index was recorded in patients with sALS (r = 0.618. r = 0.425, P < 0.01), while NO levels were significantly associated with disease progression only (r = 0.348, P < 0.01).

CONCLUSION: The data presented clearly support the role of impaired oxidant/antioxidant balance in the pathogenesis of ALS, where NO overproduction and decreased SOD defense activity seem to be particularly involved. The CSF SOD and NO level might serve as useful biomarkers for functional disorder and progression of the disease.}, } @article {pmid37633753, year = {2023}, author = {Singh, J and Habean, ML and Panicker, N}, title = {Inflammasome assembly in neurodegenerative diseases.}, journal = {Trends in neurosciences}, volume = {46}, number = {10}, pages = {814-831}, pmid = {37633753}, issn = {1878-108X}, support = {R00 AG066862/AG/NIA NIH HHS/United States ; }, mesh = {Humans ; *Neurodegenerative Diseases ; Inflammasomes ; *Alzheimer Disease ; *Parkinson Disease ; *Amyotrophic Lateral Sclerosis ; }, abstract = {Neurodegenerative disorders are characterized by the progressive dysfunction and death of selectively vulnerable neuronal populations, often associated with the accumulation of aggregated host proteins. Sustained brain inflammation and hyperactivation of inflammasome complexes have been increasingly demonstrated to contribute to neurodegenerative disease progression. Here, we review molecular mechanisms leading to inflammasome assembly in neurodegeneration. We focus primarily on four degenerative brain disorders in which inflammasome hyperactivation has been well documented: Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), and the spectrum of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). We discuss shared and divergent principles of inflammasome assembly across these disorders, and underscore the differences between neurodegeneration-associated inflammasome activation pathways and their peripheral-immune counterparts. We examine how aberrant assembly of inflammasome complexes may amplify pathology in neurodegeneration, including misfolded protein aggregation, and highlight prospects for neurotherapeutic interventions based on targeting inflammasome pathways.}, } @article {pmid37632964, year = {2023}, author = {Wang, T and Yang, X and Du, R and Zheng, S and Cui, H}, title = {Acupuncture in the Treatment of Amyotrophic Lateral Sclerosis: A Research Progress in Clinical Trials.}, journal = {Alternative therapies in health and medicine}, volume = {29}, number = {7}, pages = {114-118}, pmid = {37632964}, issn = {1078-6791}, abstract = {BACKGROUND: Acupuncture, a complementary and alternative medicine (CAM) modality, shows promise as an integrative therapy for Amyotrophic Lateral Sclerosis (ALS) due to the chronic nature of the disease and its persistent symptoms. Many patients turn to CAM for ALS treatment.

OBJECTIVE: This review assesses acupuncture's efficacy in treating Amyotrophic Lateral Sclerosis.

METHODS: We searched China National Knowledge Network (CNKI) and PubMed databases for Chinese and English articles, including clinical trials, case studies, cohorts, and randomized controlled trials. The search, performed on March 31, 2023, encompassed literature published up to that date. Keywords used in titles and abstracts were (acupuncture) OR (electro-acupuncture)) AND (Amyotrophic Lateral Sclerosis).

RESULTS: Among the 45 articles studied, 34 were included in this research. Acupuncture's benefits primarily lie in neuro-immune system regulation, enhanced quality of life, reduced fatigue, disease progression delay, and fewer relapses.

CONCLUSIONS: Recent clinical trials highlight the potential of traditional Chinese acupuncture in improving Amyotrophic Lateral Sclerosis symptoms (e.g., fatigue, neural functional deficits) and curtailing relapses. Consequently, acupuncture holds promise as an integrative therapy for ALS patients.}, } @article {pmid37631001, year = {2023}, author = {Yan, J and Bading, H}, title = {The Disruption of NMDAR/TRPM4 Death Signaling with TwinF Interface Inhibitors: A New Pharmacological Principle for Neuroprotection.}, journal = {Pharmaceuticals (Basel, Switzerland)}, volume = {16}, number = {8}, pages = {}, pmid = {37631001}, issn = {1424-8247}, abstract = {With the discovery that the acquisition of toxic features by extrasynaptic NMDA receptors (NMDARs) involves their physical interaction with the non-selective cation channel, TRPM4, it has become possible to develop a new pharmacological principle for neuroprotection, namely the disruption of the NMDAR/TRPM4 death signaling complex. This can be accomplished through the expression of the TwinF domain, a 57-amino-acid-long stretch of TRPM4 that mediates its interaction with NMDARs, but also using small molecule TwinF interface (TI) inhibitors, also known as NMDAR/TRPM4 interaction interface inhibitors. Both TwinF and small molecule TI inhibitors detoxify extrasynaptic NMDARs without interfering with synaptic NMDARs, which serve important physiological functions in the brain. As the toxic signaling of extrasynaptic NMDARs contributes to a wide range of neurodegenerative conditions, TI inhibitors may offer therapeutic options for currently untreatable human neurodegenerative diseases including Amyotrophic Lateral Sclerosis, Alzheimer's disease, and Huntington's disease.}, } @article {pmid37629277, year = {2023}, author = {Fernandes, F and Barbalho, I and Bispo Júnior, A and Alves, L and Nagem, D and Lins, H and Arrais Júnior, E and Coutinho, KD and Morais, AHF and Santos, JPQ and Machado, GM and Henriques, J and Teixeira, C and Dourado Júnior, MET and Lindquist, ARR and Valentim, RAM}, title = {Digital Alternative Communication for Individuals with Amyotrophic Lateral Sclerosis: What We Have.}, journal = {Journal of clinical medicine}, volume = {12}, number = {16}, pages = {}, pmid = {37629277}, issn = {2077-0383}, support = {132/2018//Brazilian Ministry of Health/ ; 132/2018//Norte-Grandense Foundation for Research and Culture and the Federal University of Rio Grande do Norte (FUNPEC)/ ; }, abstract = {Amyotrophic Lateral Sclerosis is a disease that compromises the motor system and the functional abilities of the person in an irreversible way, causing the progressive loss of the ability to communicate. Tools based on Augmentative and Alternative Communication are essential for promoting autonomy and improving communication, life quality, and survival. This Systematic Literature Review aimed to provide evidence on eye-image-based Human-Computer Interaction approaches for the Augmentative and Alternative Communication of people with Amyotrophic Lateral Sclerosis. The Systematic Literature Review was conducted and guided following a protocol consisting of search questions, inclusion and exclusion criteria, and quality assessment, to select primary studies published between 2010 and 2021 in six repositories: Science Direct, Web of Science, Springer, IEEE Xplore, ACM Digital Library, and PubMed. After the screening, 25 primary studies were evaluated. These studies showcased four low-cost, non-invasive Human-Computer Interaction strategies employed for Augmentative and Alternative Communication in people with Amyotrophic Lateral Sclerosis. The strategies included Eye-Gaze, which featured in 36% of the studies; Eye-Blink and Eye-Tracking, each accounting for 28% of the approaches; and the Hybrid strategy, employed in 8% of the studies. For these approaches, several computational techniques were identified. For a better understanding, a workflow containing the development phases and the respective methods used by each strategy was generated. The results indicate the possibility and feasibility of developing Human-Computer Interaction resources based on eye images for Augmentative and Alternative Communication in a control group. The absence of experimental testing in people with Amyotrophic Lateral Sclerosis reiterates the challenges related to the scalability, efficiency, and usability of these technologies for people with the disease. Although challenges still exist, the findings represent important advances in the fields of health sciences and technology, promoting a promising future with possibilities for better life quality.}, } @article {pmid37629005, year = {2023}, author = {La Cognata, V and D'Amico, AG and Maugeri, G and Morello, G and Guarnaccia, M and Magrì, B and Aronica, E and Alkon, DL and D'Agata, V and Cavallaro, S}, title = {The ε-Isozyme of Protein Kinase C (PKCε) Is Impaired in ALS Motor Cortex and Its Pulse Activation by Bryostatin-1 Produces Long Term Survival in Degenerating SOD1-G93A Motor Neuron-like Cells.}, journal = {International journal of molecular sciences}, volume = {24}, number = {16}, pages = {}, pmid = {37629005}, issn = {1422-0067}, support = {DSB.AD007.304//IRIB-CNR/ ; }, mesh = {Humans ; Protein Kinase C-epsilon/genetics ; *Amyotrophic Lateral Sclerosis/genetics ; Isoenzymes/genetics ; Superoxide Dismutase-1/genetics ; *Motor Cortex ; Bryostatins/pharmacology ; *Neurodegenerative Diseases ; Motor Neurons ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a rapidly progressive and ultimately fatal neurodegenerative disease, characterized by a progressive depletion of upper and lower motor neurons (MNs) in the brain and spinal cord. The aberrant regulation of several PKC-mediated signal transduction pathways in ALS has been characterized so far, describing either impaired expression or altered activity of single PKC isozymes (α, β, ζ and δ). Here, we detailed the distribution and cellular localization of the ε-isozyme of protein kinase C (PKCε) in human postmortem motor cortex specimens and reported a significant decrease in both PKCε mRNA (PRKCE) and protein immunoreactivity in a subset of sporadic ALS patients. We furthermore investigated the steady-state levels of both pan and phosphorylated PKCε in doxycycline-activated NSC-34 cell lines carrying the human wild-type (WT) or mutant G93A SOD1 and the biological long-term effect of its transient agonism by Bryostatin-1. The G93A-SOD1 cells showed a significant reduction of the phosphoPKCε/panPKCε ratio compared to the WT. Moreover, a brief pulse activation of PKCε by Bryostatin-1 produced long-term survival in activated G93A-SOD1 degenerating cells in two different cell death paradigms (serum starvation and chemokines-induced toxicity). Altogether, the data support the implication of PKCε in ALS pathophysiology and suggests its pharmacological modulation as a potential neuroprotective strategy, at least in a subgroup of sporadic ALS patients.}, } @article {pmid37628709, year = {2023}, author = {De Marchi, F and Tondo, G and Corrado, L and Menegon, F and Aprile, D and Anselmi, M and D'Alfonso, S and Comi, C and Mazzini, L}, title = {Neuroinflammatory Pathways in the ALS-FTD Continuum: A Focus on Genetic Variants.}, journal = {Genes}, volume = {14}, number = {8}, pages = {}, pmid = {37628709}, issn = {2073-4425}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics ; *Frontotemporal Dementia/genetics ; Neuroinflammatory Diseases ; Oxidative Stress ; Astrocytes ; Mitochondrial Proteins ; }, abstract = {Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal dementia (FDT) are progressive neurodegenerative disorders that, in several cases, overlap in clinical presentation, and genetic and pathological disease mechanisms. About 10-15% of ALS cases and up to 40% of FTD are familial, usually with dominant traits. ALS and FTD, in several cases, share common gene mutations, such as in C9ORF72, TARDBP, SQSTM-1, FUS, VCP, CHCHD10, and TBK-1. Also, several mechanisms are involved in ALS and FTD pathogenesis, such as protein misfolding, oxidative stress, and impaired axonal transport. In addition, neuroinflammation and neuroinflammatory cells, such as astrocytes, oligodendrocytes, microglia, and lymphocytes and, overall, the cellular microenvironment, have been proposed as pivotal players in the pathogenesis the ALS-FTD spectrum disorders. This review overviews the current evidence regarding neuroinflammatory markers in the ALS/FTD continuum, focusing on the neuroinflammatory pathways involved in the genetic cases, moving from post-mortem reports to in vivo biofluid and neuroimaging data. We further discuss the potential link between genetic and autoimmune disorders and potential therapeutic implications.}, } @article {pmid37627588, year = {2023}, author = {Giménez-Bejarano, A and Alegre-Cortés, E and Yakhine-Diop, SMS and Gómez-Suaga, P and Fuentes, JM}, title = {Mitochondrial Dysfunction in Repeat Expansion Diseases.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {12}, number = {8}, pages = {}, pmid = {37627588}, issn = {2076-3921}, support = {CIBERNED CB06/05/0041//Instituto de Salud Carlos III/ ; }, abstract = {Repeat expansion diseases are a group of neuromuscular and neurodegenerative disorders characterized by expansions of several successive repeated DNA sequences. Currently, more than 50 repeat expansion diseases have been described. These disorders involve diverse pathogenic mechanisms, including loss-of-function mechanisms, toxicity associated with repeat RNA, or repeat-associated non-ATG (RAN) products, resulting in impairments of cellular processes and damaged organelles. Mitochondria, double membrane organelles, play a crucial role in cell energy production, metabolic processes, calcium regulation, redox balance, and apoptosis regulation. Its dysfunction has been implicated in the pathogenesis of repeat expansion diseases. In this review, we provide an overview of the signaling pathways or proteins involved in mitochondrial functioning described in these disorders. The focus of this review will be on the analysis of published data related to three representative repeat expansion diseases: Huntington's disease, C9orf72-frontotemporal dementia/amyotrophic lateral sclerosis, and myotonic dystrophy type 1. We will discuss the common effects observed in all three repeat expansion disorders and their differences. Additionally, we will address the current gaps in knowledge and propose possible new lines of research. Importantly, this group of disorders exhibit alterations in mitochondrial dynamics and biogenesis, with specific proteins involved in these processes having been identified. Understanding the underlying mechanisms of mitochondrial alterations in these disorders can potentially lead to the development of neuroprotective strategies.}, } @article {pmid37627315, year = {2023}, author = {Kandeel, M and Morsy, MA and Alkhodair, KM and Alhojaily, S}, title = {Mesenchymal Stem Cell-Derived Extracellular Vesicles: An Emerging Diagnostic and Therapeutic Biomolecules for Neurodegenerative Disabilities.}, journal = {Biomolecules}, volume = {13}, number = {8}, pages = {}, pmid = {37627315}, issn = {2218-273X}, mesh = {Adult ; Humans ; *Amyotrophic Lateral Sclerosis ; *Mesenchymal Stem Cells ; *Adult Stem Cells ; *Alzheimer Disease ; *Extracellular Vesicles ; *Huntington Disease ; *Multiple Sclerosis ; *Parkinson Disease/diagnosis/therapy ; }, abstract = {Mesenchymal stem cells (MSCs) are a type of versatile adult stem cells present in various organs. These cells give rise to extracellular vesicles (EVs) containing a diverse array of biologically active elements, making them a promising approach for therapeutics and diagnostics. This article examines the potential therapeutic applications of MSC-derived EVs in addressing neurodegenerative disorders such as Alzheimer's disease (AD), multiple sclerosis (MS), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD). Furthermore, the present state-of-the-art for MSC-EV-based therapy in AD, HD, PD, ALS, and MS is discussed. Significant progress has been made in understanding the etiology and potential treatments for a range of neurodegenerative diseases (NDs) over the last few decades. The contents of EVs are carried across cells for intercellular contact, which often results in the control of the recipient cell's homeostasis. Since EVs represent the therapeutically beneficial cargo of parent cells and are devoid of many ethical problems connected with cell-based treatments, they offer a viable cell-free therapy alternative for tissue regeneration and repair. Developing innovative EV-dependent medicines has proven difficult due to the lack of standardized procedures in EV extraction processes as well as their pharmacological characteristics and mechanisms of action. However, recent biotechnology and engineering research has greatly enhanced the content and applicability of MSC-EVs.}, } @article {pmid37627263, year = {2023}, author = {Rühmkorf, A and Harbauer, AB}, title = {Role of Mitochondria-ER Contact Sites in Mitophagy.}, journal = {Biomolecules}, volume = {13}, number = {8}, pages = {}, pmid = {37627263}, issn = {2218-273X}, mesh = {Humans ; *Mitophagy ; Mitochondria ; Mitochondrial Membranes ; *Amyotrophic Lateral Sclerosis ; Apoptosis ; Mitochondrial Proteins ; Receptors, Estrogen ; }, abstract = {Mitochondria are often referred to as the "powerhouse" of the cell. However, this organelle has many more functions than simply satisfying the cells' metabolic needs. Mitochondria are involved in calcium homeostasis and lipid metabolism, and they also regulate apoptotic processes. Many of these functions require contact with the ER, which is mediated by several tether proteins located on the respective organellar surfaces, enabling the formation of mitochondria-ER contact sites (MERCS). Upon damage, mitochondria produce reactive oxygen species (ROS) that can harm the surrounding cell. To circumvent toxicity and to maintain a functional pool of healthy organelles, damaged and excess mitochondria can be targeted for degradation via mitophagy, a form of selective autophagy. Defects in mitochondria-ER tethers and the accumulation of damaged mitochondria are found in several neurodegenerative diseases, including Parkinson's disease and amyotrophic lateral sclerosis, which argues that the interplay between the two organelles is vital for neuronal health. This review provides an overview of the different mechanisms of mitochondrial quality control that are implicated with the different mitochondria-ER tether proteins, and also provides a novel perspective on how MERCS are involved in mediating mitophagy upon mitochondrial damage.}, } @article {pmid37627248, year = {2023}, author = {Belo do Nascimento, I and Ates, G and Desmet, N and Beckers, P and Massie, A and Hermans, E}, title = {AMPKα1 Deficiency in Astrocytes from a Rat Model of ALS Is Associated with an Altered Metabolic Resilience.}, journal = {Biomolecules}, volume = {13}, number = {8}, pages = {}, pmid = {37627248}, issn = {2218-273X}, mesh = {Rats ; Animals ; *Amyotrophic Lateral Sclerosis/genetics ; Astrocytes ; AMP-Activated Protein Kinases ; Motor Neurons ; Glutamic Acid ; Superoxide Dismutase-1/genetics ; Adenosine Triphosphate ; }, abstract = {Alterations in the activity of the regulator of cell metabolism AMP-activated protein kinase (AMPK) have been reported in motor neurons from patients and animal models of amyotrophic lateral sclerosis (ALS). Considering the key role played by astrocytes in modulating energy metabolism in the nervous system and their compromised support towards neurons in ALS, we examined whether a putative alteration in AMPK expression/activity impacted astrocytic functions such as their metabolic plasticity and glutamate handling capacity. We found a reduced expression of AMPK mRNA in primary cultures of astrocytes derived from transgenic rats carrying an ALS-associated mutated superoxide dismutase (hSOD1[G93A]). The activation of AMPK after glucose deprivation was reduced in hSOD1[G93A] astrocytes compared to non-transgenic. This was accompanied by a lower increase in ATP levels and increased vulnerability to this insult, although the ATP production rate did not differ between the two cell types. Furthermore, soliciting the activity of glutamate transporters was found to induce similar AMPK activity in these cells. However, manipulation of AMPK activity did not influence glutamate transport. Together, these results suggest that the altered AMPK responsiveness in ALS might be context dependent and may compromise the metabolic adaptation of astrocytes in response to specific cellular stress.}, } @article {pmid37626868, year = {2023}, author = {Guerra, M and Meola, L and Lattante, S and Conte, A and Sabatelli, M and Sette, C and Bernardini, C}, title = {Characterization of SOD1-DT, a Divergent Long Non-Coding RNA in the Locus of the SOD1 Human Gene.}, journal = {Cells}, volume = {12}, number = {16}, pages = {}, pmid = {37626868}, issn = {2073-4409}, mesh = {Humans ; *RNA, Long Noncoding/genetics ; Superoxide Dismutase-1/genetics ; *Amyotrophic Lateral Sclerosis/genetics ; *Neuroblastoma ; Alleles ; }, abstract = {Researchers studying Amyotrophic Lateral Sclerosis (ALS) have made significant efforts to find a unique mechanism to explain the etiopathology of the different forms of the disease. However, despite several mutations associated with ALS having been discovered in recent years, the link between the mutated genes and its onset has not yet been fully elucidated. Among the genes associated with ALS, superoxide dismutase 1 (SOD1) was the first to be identified, but its role in the etiopathogenesis of the disease is still unclear. In recent years, research has been focused on the non-coding part of the genome to fully understand the mechanisms underlying gene regulation. Non-coding RNAs are conserved molecules and are not usually translated in protein. A total of 98% of the human genome is composed of non-protein coding sequences with roles in the transcriptional and post-transcriptional regulation of gene expression. In this study, we characterized a divergent nuclear lncRNA (SOD1-DT) transcribed in the antisense direction from the 5' region of the SOD1 coding gene in both the SH-SY5Y cell line and fibroblasts derived from ALS patients. Interestingly, this lncRNA seems to regulate gene expression, since its inhibition leads to the upregulation of surrounding genes including SOD1. SOD1-DT represents a very complex molecule, displaying allelic and transcriptional variability concerning transposable elements (TEs) included in its sequence, widening the scenario of gene expression regulation in ALS disease.}, } @article {pmid37626649, year = {2023}, author = {Younes, R and Issa, Y and Jdaa, N and Chouaib, B and Brugioti, V and Challuau, D and Raoul, C and Scamps, F and Cuisinier, F and Hilaire, C}, title = {The Secretome of Human Dental Pulp Stem Cells and Its Components GDF15 and HB-EGF Protect Amyotrophic Lateral Sclerosis Motoneurons against Death.}, journal = {Biomedicines}, volume = {11}, number = {8}, pages = {}, pmid = {37626649}, issn = {2227-9059}, support = {R20071FF//ARSLA/ ; 0000//Délégation Régionale Occitanie Méditerranée/ ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal and incurable paralytic disorder caused by the progressive death of upper and lower motoneurons. Although numerous strategies have been developed to slow disease progression and improve life quality, to date only a few therapeutic treatments are available with still unsatisfactory therapeutic benefits. The secretome of dental pulp stem cells (DPSCs) contains numerous neurotrophic factors that could promote motoneuron survival. Accordingly, DPSCs confer neuroprotective benefits to the SOD1[G93A] mouse model of ALS. However, the mode of action of DPSC secretome on motoneurons remains largely unknown. Here, we used conditioned medium of human DPSCs (DPSCs-CM) and assessed its effect on survival, axonal length, and electrical activity of cultured wildtype and SOD1[G93A] motoneurons. To further understand the role of individual factors secreted by DPSCs and to circumvent the secretome variability bias, we focused on GDF15 and HB-EGF whose neuroprotective properties remain elusive in the ALS pathogenic context. DPSCs-CM rescues motoneurons from trophic factor deprivation-induced death, promotes axon outgrowth of wildtype but not SOD1[G93A] mutant motoneurons, and has no impact on the spontaneous electrical activity of wildtype or mutant motoneurons. Both GDF15 and HB-EGF protect SOD1[G93A] motoneurons against nitric oxide-induced death, but not against death induced by trophic factor deprivation. GDF15 and HB-EGF receptors were found to be expressed in the spinal cord, with a two-fold increase in expression for the GDF15 low-affinity receptor in SOD1[G93A] mice. Therefore, the secretome of DPSCs appears as a new potential therapeutic candidate for ALS.}, } @article {pmid37626421, year = {2023}, author = {Wang, S and Sun, S}, title = {Translation dysregulation in neurodegenerative diseases: a focus on ALS.}, journal = {Molecular neurodegeneration}, volume = {18}, number = {1}, pages = {58}, pmid = {37626421}, issn = {1750-1326}, support = {R21 AG072078/AG/NIA NIH HHS/United States ; R01 NS107347/NS/NINDS NIH HHS/United States ; RF1 NS113820/NS/NINDS NIH HHS/United States ; RF1 NS127925/NS/NINDS NIH HHS/United States ; R01 AG078948/AG/NIA NIH HHS/United States ; }, mesh = {Humans ; *Neurodegenerative Diseases/genetics ; *Amyotrophic Lateral Sclerosis/genetics ; Nerve Degeneration ; Homeostasis ; RNA ; }, abstract = {RNA translation is tightly controlled in eukaryotic cells to regulate gene expression and maintain proteome homeostasis. RNA binding proteins, translation factors, and cell signaling pathways all modulate the translation process. Defective translation is involved in multiple neurological diseases including amyotrophic lateral sclerosis (ALS). ALS is a progressive neurodegenerative disorder and poses a major public health challenge worldwide. Over the past few years, tremendous advances have been made in the understanding of the genetics and pathogenesis of ALS. Dysfunction of RNA metabolisms, including RNA translation, has been closely associated with ALS. Here, we first introduce the general mechanisms of translational regulation under physiological and stress conditions and review well-known examples of translation defects in neurodegenerative diseases. We then focus on ALS-linked genes and discuss the recent progress on how translation is affected by various mutant genes and the repeat expansion-mediated non-canonical translation in ALS.}, } @article {pmid37622689, year = {2024}, author = {Dey, B and Kumar, A and Patel, AB}, title = {Pathomechanistic Networks of Motor System Injury in Amyotrophic Lateral Sclerosis.}, journal = {Current neuropharmacology}, volume = {22}, number = {11}, pages = {1778-1806}, pmid = {37622689}, issn = {1875-6190}, support = {DST/CSRI/2017/258//Department of Science and Technology (DST), Govt. of India/ ; DBT/JRF/BET-17/1/2017/AL/400//Department of Biotechnology (DBT), Govt. of India/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/genetics/metabolism ; Humans ; Animals ; Gene-Environment Interaction ; Motor Neurons/metabolism/pathology ; }, abstract = {Amyotrophic Lateral Sclerosis (ALS) is the most common, adult-onset, progressive motor neurodegenerative disorder that results in death within 3 years of the clinical diagnosis. Due to the clinicopathological heterogeneity, any reliable biomarkers for diagnosis or prognosis of ALS have not been identified till date. Moreover, the only three clinically approved treatments are not uniformly effective in slowing the disease progression. Over the last 15 years, there has been a rapid advancement in research on the complex pathomechanistic landscape of ALS that has opened up new avenues for successful clinical translation of targeted therapeutics. Multiple studies suggest that the age-dependent interaction of risk-associated genes with environmental factors and endogenous modifiers is critical to the multi-step process of ALS pathogenesis. In this review, we provide an updated discussion on the dysregulated cross-talk between intracellular homeostasis processes, the unique molecular networks across selectively vulnerable cell types, and the multisystemic nature of ALS pathomechanisms. Importantly, this work highlights the alteration in epigenetic and epitranscriptomic landscape due to gene-environment interactions, which have been largely overlooked in the context of ALS pathology. Finally, we suggest that precision medicine research in ALS will be largely benefitted from the stratification of patient groups based on the clinical phenotype, onset and progression, genome, exposome, and metabolic identities.}, } @article {pmid37621312, year = {2023}, author = {Sun, Z and Liu, X and Zuo, W and Fu, Q and Xu, T and Cui, L and Zhang, B and Peng, Y}, title = {Development of a robust UPLC-MS/MS method for the quantification of riluzole in human plasma and its application in pharmacokinetics.}, journal = {Frontiers in pharmacology}, volume = {14}, number = {}, pages = {1227354}, pmid = {37621312}, issn = {1663-9812}, abstract = {Introduction: The aim of the present study was to establish a simple method for the determination of riluzole in human plasma by ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and apply it for the determination of riluzole in amyotrophic lateral sclerosis (ALS) patients. Methods: Samples were prepared by protein precipitation and were then gradient-eluted on a column of ACQUITY UPLC[®] HSS T3 by using 0.1% formic acid acetonitrile and 0.1% formic acid water as the mobile phase. Detection was performed on a Xevo TQ-S tandem mass spectrometer in the multiple-reaction monitoring mode using positive electrospray ionization. Validation was performed in the range of 5-800 ng/mL. Results and discussion: Three batches of precision accuracy, selectivity, matrix effects, extraction recovery, and stability were also verified and met the requirements. The results showed that the method was reliable and successfully applied to the pharmacokinetics study of riluzole in Chinese amyotrophic lateral sclerosis patients. Meanwhile, in comparison with other prior published methods, our method has the advantages of simple sample preparation, relatively short running time, and small plasma sample consumption, which represented a high-throughput sample determination potential.}, } @article {pmid37620418, year = {2023}, author = {Artuğ, NT}, title = {Fully automated F-wave corridor extraction and analysis algorithm for F-wave analyses and MUNE studies.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {13822}, pmid = {37620418}, issn = {2045-2322}, mesh = {Humans ; *Algorithms ; Software ; Foot ; *Poliomyelitis/diagnosis ; Thumb ; }, abstract = {F-waves are used in motor unit number estimation (MUNE) studies, which require rapid dedicated software to perform calculations. The aim of this study is to define a mathematical method for a fully automated F-wave extraction algorithm to perform F-wave and MUNE studies while performing baseline corrections without distorting traces. Ten recordings from each class, such as healthy controls, polio patients and ALS patients, were included. Submaximal stimuli were applied to the median and ulnar nerves to record 300 traces from the abductor pollicis brevis and abductor digiti minimi muscles. The autocorrelation function and the signal of sum of all traces were used to find the location for the maximum amplitude of the F-waves. F-waves were revealed by using a cutting window. Linear line estimation was preferred for baseline corrections because it did not cause any distortion in the traces. The algorithm automatically revealed F-waves from all 30 recordings in accordance with the locations marked by a neurophysiologist. The execution of the algorithm was less than 2 (usually < 1) minutes when 300 traces were analyzed. Mean sMUP amplitudes and MUNE values are important for differentiating healthy controls from patients. Moreover, F-wave parameters belonging to polio patients on whom there was a relatively low number of studies conducted were also evaluated.}, } @article {pmid37620323, year = {2023}, author = {Krebs, AS and Liu, HF and Zhou, Y and Rey, JS and Levintov, L and Shen, J and Howe, A and Perilla, JR and Bartesaghi, A and Zhang, P}, title = {Molecular architecture and conservation of an immature human endogenous retrovirus.}, journal = {Nature communications}, volume = {14}, number = {1}, pages = {5149}, pmid = {37620323}, issn = {2041-1723}, support = {/WT_/Wellcome Trust/United Kingdom ; R01 AI157843/AI/NIAID NIH HHS/United States ; R01 GM141223/GM/NIGMS NIH HHS/United States ; U54 AI170791/AI/NIAID NIH HHS/United States ; }, mesh = {Humans ; *Endogenous Retroviruses/genetics ; *Amyotrophic Lateral Sclerosis ; Biological Evolution ; Capsid ; Capsid Proteins/genetics ; }, abstract = {The human endogenous retrovirus K (HERV-K) is the most recently acquired endogenous retrovirus in the human genome and is activated and expressed in many cancers and amyotrophic lateral sclerosis. We present the immature HERV-K capsid structure at 3.2 Å resolution determined from native virus-like particles using cryo-electron tomography and subtomogram averaging. The structure shows a hexamer unit oligomerized through a 6-helix bundle, which is stabilized by a small molecule analogous to IP6 in immature HIV-1 capsid. The HERV-K immature lattice is assembled via highly conserved dimer and trimer interfaces, as detailed through all-atom molecular dynamics simulations and supported by mutational studies. A large conformational change mediated by the linker between the N-terminal and the C-terminal domains of CA occurs during HERV-K maturation. Comparison between HERV-K and other retroviral immature capsid structures reveals a highly conserved mechanism for the assembly and maturation of retroviruses across genera and evolutionary time.}, } @article {pmid37620293, year = {2023}, author = {Kuiper, EFE and Prophet, SM and Schlieker, C}, title = {Coordinating nucleoporin condensation and nuclear pore complex assembly.}, journal = {FEBS letters}, volume = {597}, number = {20}, pages = {2534-2545}, doi = {10.1002/1873-3468.14725}, pmid = {37620293}, issn = {1873-3468}, support = {//Dystonia Medical Research Foundation/ ; ALTF 910-2022//European Molecular Biology Organization/ ; 019.222EN.007//Nederlandse Organisatie voor Wetenschappelijk Onderzoek/ ; PR200788//U.S. Department of Defense/ ; }, abstract = {The nuclear pore complex (NPC) is among the most elaborate protein complexes in eukaryotes. While ribosomes and proteasomes are known to require dedicated assembly machinery, our understanding of NPC assembly is at a relatively early stage. Defects in NPC assembly or homeostasis are tied to movement disorders, including dystonia and amyotrophic lateral sclerosis (ALS), as well as aging, requiring a better understanding of these processes to enable therapeutic intervention. Here, we discuss recent progress in the understanding of NPC assembly and highlight how related defects in human disorders can shed light on NPC biogenesis. We propose that the condensation of phenylalanine-glycine repeat nucleoporins needs to be carefully controlled during NPC assembly to prevent aberrant condensation, aggregation, or amyloid formation.}, } @article {pmid37620092, year = {2023}, author = {Fink, JK}, title = {The hereditary spastic paraplegias.}, journal = {Handbook of clinical neurology}, volume = {196}, number = {}, pages = {59-88}, doi = {10.1016/B978-0-323-98817-9.00022-3}, pmid = {37620092}, issn = {0072-9752}, mesh = {Child, Preschool ; Humans ; *Spastic Paraplegia, Hereditary/genetics ; Biological Transport ; *Cerebral Palsy ; Exercise ; Family ; }, abstract = {The hereditary spastic paraplegias (HSPs) are a group of more than 90 genetic disorders in which lower extremity spasticity and weakness are either the primary neurologic impairments ("uncomplicated HSP") or when accompanied by other neurologic deficits ("complicated HSP"), important features of the clinical syndrome. Various genetic types of HSP are inherited such as autosomal dominant, autosomal recessive, X-linked, and maternal (mitochondrial) traits. Symptoms that begin in early childhood may be nonprogressive and resemble spastic diplegic cerebral palsy. Symptoms that begin later, typically progress insidiously over a number of years. Genetic testing is able to confirm the diagnosis for many subjects. Insights from gene discovery indicate that abnormalities in diverse molecular processes underlie various forms of HSP, including disturbance in axon transport, endoplasmic reticulum morphogenesis, vesicle transport, lipid metabolism, and mitochondrial function. Pathologic studies in "uncomplicated" HSP have shown axon degeneration particularly involving the distal ends of corticospinal tracts and dorsal column fibers. Treatment is limited to symptom reduction including amelioration of spasticity, reducing urinary urgency, proactive physical therapy including strengthening, stretching, balance, and agility exercise.}, } @article {pmid37620088, year = {2023}, author = {Muzio, L and Ghirelli, A and Agosta, F and Martino, G}, title = {Novel therapeutic approaches for motor neuron disease.}, journal = {Handbook of clinical neurology}, volume = {196}, number = {}, pages = {523-537}, doi = {10.1016/B978-0-323-98817-9.00027-2}, pmid = {37620088}, issn = {0072-9752}, mesh = {Animals ; Humans ; *Neurodegenerative Diseases ; *Motor Neuron Disease/therapy ; *Amyotrophic Lateral Sclerosis/therapy ; Motor Neurons ; Cognition ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that leads to the neurodegeneration and death of upper and lower motor neurons (MNs). Although MNs are the main cells involved in the process of neurodegeneration, a growing body of evidence points toward other cell types as concurrent to disease initiation and propagation. Given the current absence of effective therapies, the quest for other therapeutic targets remains open and still challenges the scientific community. Both neuronal and extra-neuronal mechanisms of cellular stress and damage have been studied and have posed the basis for the development of novel therapies that have been investigated on both animal models and humans. In this chapter, a thorough review of the main mechanisms of cellular damage and the respective therapeutic attempts targeting them is reported. The main areas covered include neuroinflammation, protein aggregation, RNA metabolism, and oxidative stress.}, } @article {pmid37620070, year = {2023}, author = {Younger, DS and Brown, RH}, title = {Amyotrophic lateral sclerosis.}, journal = {Handbook of clinical neurology}, volume = {196}, number = {}, pages = {203-229}, doi = {10.1016/B978-0-323-98817-9.00031-4}, pmid = {37620070}, issn = {0072-9752}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/therapy ; Motor Neurons ; Syndrome ; }, abstract = {The scientific landscape surrounding amyotrophic lateral sclerosis has shifted immensely with a number of well-defined ALS disease-causing genes, each with related phenotypical and cellular motor neuron processes that have come to light. Yet in spite of decades of research and clinical investigation, there is still no etiology for sporadic amyotrophic lateral sclerosis, and treatment options even for those with well-defined familial syndromes are still limited. This chapter provides a comprehensive review of the genetic basis of amyotrophic lateral sclerosis, highlighting factors that contribute to its heritability and phenotypic manifestations, and an overview of past, present, and upcoming therapeutic strategies.}, } @article {pmid37619957, year = {2023}, author = {Chaves-Filho, AB and Diniz, LS and Santos, RS and Lima, RS and Oreliana, H and Pinto, IFD and Dantas, LS and Inague, A and Faria, RL and Medeiros, MHG and Glezer, I and Festuccia, WT and Yoshinaga, MY and Miyamoto, S}, title = {Plasma oxylipin profiling by high resolution mass spectrometry reveal signatures of inflammation and hypermetabolism in amyotrophic lateral sclerosis.}, journal = {Free radical biology & medicine}, volume = {208}, number = {}, pages = {285-298}, doi = {10.1016/j.freeradbiomed.2023.08.019}, pmid = {37619957}, issn = {1873-4596}, mesh = {Rats ; Humans ; Animals ; Mice ; *Amyotrophic Lateral Sclerosis/genetics/metabolism ; Oxylipins ; *Neurodegenerative Diseases ; Mass Spectrometry ; Superoxide Dismutase-1/genetics/metabolism ; Inflammation ; Disease Models, Animal ; Mice, Transgenic ; Superoxide Dismutase/genetics ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive loss of motor neurons, systemic hypermetabolism, and inflammation. In this context, oxylipins have been investigated as signaling molecules linked to neurodegeneration, although their specific role in ALS remains unclear. Importantly, most methods focused on oxylipin analysis are based on low-resolution mass spectrometry, which usually confers high sensitivity, but not great accuracy for molecular characterization, as provided by high-resolution MS (HRMS). Here, we established an ultra-high performance liquid chromatography HRMS (LC-HRMS) method for simultaneous analysis of 126 oxylipins in plasma. Intra- and inter-day method validation showed high sensitivity (0.3-25 pg), accuracy and precision for more than 90% of quality controls. This method was applied in plasma of ALS rats overexpressing the mutant human Cu/Zn-superoxide dismutase gene (SOD1-G93A) at asymptomatic (ALS 70 days old) and symptomatic stages (ALS 120 days old), and their respective age-matched wild type controls. From the 56 oxylipins identified in plasma, 17 species were significantly altered. Remarkably, most of oxylipins linked to inflammation and oxidative stress derived from arachidonic acid (AA), like prostaglandins and mono-hydroxides, were increased in ALS 120 d rats. In addition, ketones derived from AA and linoleic acid (LA) were increased in both WT 120 d and ALS 120 d groups, supporting that age also modulates oxylipin metabolism in plasma. Interestingly, the LA-derived diols involved in fatty acid uptake and β-oxidation, 9(10)-DiHOME and 12(13)-DiHOME, were decreased in ALS 120 d rats and showed significant synergic effects between age and disease factors. In summary, we validated a high-throughput LC-HRMS method for oxylipin analysis and provided a comprehensive overview of plasma oxylipins involved in ALS disease progression. Noteworthy, the oxylipins altered in plasma have potential to be investigated as biomarkers for inflammation and hypermetabolism in ALS.}, } @article {pmid37619619, year = {2023}, author = {Wang, Y and Lv, MN and Zhao, WJ}, title = {Research on ferroptosis as a therapeutic target for the treatment of neurodegenerative diseases.}, journal = {Ageing research reviews}, volume = {91}, number = {}, pages = {102035}, doi = {10.1016/j.arr.2023.102035}, pmid = {37619619}, issn = {1872-9649}, mesh = {Humans ; *Neurodegenerative Diseases/metabolism ; *Ferroptosis ; *Alzheimer Disease/drug therapy ; *Parkinson Disease/drug therapy ; *Huntington Disease ; }, abstract = {Ferroptosis is an iron- and lipid peroxidation (LPO)-mediated programmed cell death type. Recently, mounting evidence has indicated the involvement of ferroptosis in neurodegenerative diseases, especially in Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), and so on. Treating ferroptosis presents opportunities as well as challenges for neurodegenerative diseases. This review provides a comprehensive overview of typical features of ferroptosis and the underlying mechanisms that contribute to its occurrence, as well as their implications in the pathogenesis and advancement of major neurodegenerative disorders. Meanwhile, we summarize the utilization of ferroptosis inhibition in both experimental and clinical approaches for the treatment of major neurodegenerative disorders. In addition, we specifically summarize recent advances in developing therapeutic means targeting ferroptosis in these diseases, which may guide future approaches for the effective management of these devastating medical conditions.}, } @article {pmid37619554, year = {2023}, author = {Cheesbrough, A and Harley, P and Riccio, F and Wu, L and Song, W and Lieberam, I}, title = {A scalable human iPSC-based neuromuscular disease model on suspended biobased elastomer nanofiber scaffolds.}, journal = {Biofabrication}, volume = {15}, number = {4}, pages = {}, pmid = {37619554}, issn = {1758-5090}, support = {BB/M009513/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; /DH_/Department of Health/United Kingdom ; MR/W006251/1/MRC_/Medical Research Council/United Kingdom ; MR/N026063/1/MRC_/Medical Research Council/United Kingdom ; 108874/Z/15/Z/WT_/Wellcome Trust/United Kingdom ; WT098503/WT_/Wellcome Trust/United Kingdom ; MR/N025865/1/MRC_/Medical Research Council/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis ; *Induced Pluripotent Stem Cells ; *Nanofibers ; Elastomers ; *Neuromuscular Diseases ; }, abstract = {Many devastating neuromuscular diseases currently lack effective treatments. This is in part due to a lack of drug discovery platforms capable of assessing complex human neuromuscular disease phenotypes in a scalable manner. A major obstacle has been generating scaffolds to stabilise mature contractile myofibers in a multi-well assay format amenable to high content image (HCI) analysis. This study describes the development of a scalable human induced pluripotent stem cell (iPSC)-neuromuscular disease model, whereby suspended elastomer nanofibers support long-term stability, alignment, maturation, and repeated contractions of iPSC-myofibers, innervated by iPSC-motor neurons in 96-well assay plates. In this platform, optogenetic stimulation of the motor neurons elicits robust myofiber-contractions, providing a functional readout of neuromuscular transmission. Additionally, HCI analysis provides rapid and automated quantification of axonal outgrowth, myofiber morphology, and neuromuscular synapse number and morphology. By incorporating amyotrophic lateral sclerosis (ALS)-related TDP-43[G298S]mutant motor neurons and CRISPR-corrected controls, key neuromuscular disease phenotypes are recapitulated, including weaker myofiber contractions, reduced axonal outgrowth, and reduced number of neuromuscular synapses. Treatment with a candidate ALS drug, the receptor-interacting protein kinase-1 (RIPK1)-inhibitor necrostatin-1, rescues these phenotypes in a dose-dependent manner, highlighting the potential of this platform to screen novel treatments for neuromuscular diseases.}, } @article {pmid37615876, year = {2023}, author = {Kobayashi, H and Ueda, K and Morimoto, S and Ishikawa, M and Leventoux, N and Sasaki, R and Hirokawa, Y and Kokubo, Y and Okano, H}, title = {Protein profiling of extracellular vesicles from iPSC-derived astrocytes of patients with ALS/PDC in Kii peninsula.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {44}, number = {12}, pages = {4511-4516}, pmid = {37615876}, issn = {1590-3478}, support = {JP15J03921//Japan Society for the Promotion of Science/ ; JP18K07368//Japan Society for the Promotion of Science/ ; JP18KK0239//Japan Society for the Promotion of Science/ ; JP19K17002//Japan Society for the Promotion of Science/ ; JP19K08002//Japan Society for the Promotion of Science/ ; JP21H05278//Japan Society for the Promotion of Science/ ; JP22K15736//Japan Society for the Promotion of Science/ ; JP25305030//Japan Society for the Promotion of Science/ ; JP15K09364//Japan Society for the Promotion of Science/ ; JP17H01689//Japan Society for the Promotion of Science/ ; JP18K07514//Japan Society for the Promotion of Science/ ; JP20H00485//Japan Society for the Promotion of Science/ ; JP21F21410//Japan Society for the Promotion of Science/ ; JP21H05273//Japan Society for the Promotion of Science/ ; JP22KF0333//Japan Society for the Promotion of Science/ ; JP23kk0305024//Japan Agency for Medical Research and Development/ ; JP23bm1123046//Japan Agency for Medical Research and Development/ ; 17ek0109139h0003//Japan Agency for Medical Research and Development/ ; JP22bm0804003//Japan Agency for Medical Research and Development/ ; JP20ek0109395//Japan Agency for Medical Research and Development/ ; JP20ek0109329//Japan Agency for Medical Research and Development/ ; JP21wm0425009//Japan Agency for Medical Research and Development/ ; JP23bm1423002//Japan Agency for Medical Research and Development/ ; 21210301//Ministry of Health, Labour and Welfare/ ; H29-Nanchi- Ippan-085//Ministry of Health, Labour and Welfare/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/epidemiology ; *Induced Pluripotent Stem Cells/metabolism/pathology ; *Neurodegenerative Diseases ; Astrocytes/pathology ; Proteome ; Japan/epidemiology ; *Extracellular Vesicles/metabolism/pathology ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis/Parkinsonism-dementia complex in Kii peninsula, Japan (Kii ALS/PDC), is an endemic neurodegenerative disease whose causes and pathogenesis remain unknown. However, astrocytes in autopsied cases of Kii ALS/PDC show characteristic lesions. In addition, relationships between extracellular vesicles (EVs) and neurodegenerative diseases are increasingly apparent. Therefore, we focused on proteins in EVs derived from Kii ALS/PDC astrocytes in the present study.

METHODS: Induced pluripotent stem cells (iPSCs) derived from three healthy controls (HCs) and three patients with Kii ALS/PDC were differentiated into astrocytes. EVs in the culture medium of astrocytes were collected and subjected to quantitative proteome analysis.

RESULTS: Our proteome analysis reveals that EV-containing proteins derived from astrocytes of patients with Kii ALS/PDC show distinctive patterns compared with those of HCs. Moreover, EVs derived from Kii ALS/PDC astrocytes display increased proteins related to proteostasis and decreased proteins related to anti-inflammation.

DISCUSSION: Proteins contained in EVs from astrocytes unveil protective support to neurons and may reflect the molecular pathomechanism of Kii ALS/PDC; accordingly, they may be potential biomarker candidates of Kii ALS/PDC.}, } @article {pmid37615751, year = {2023}, author = {Ortholand, J and Pradat, PF and Tezenas du Montcel, S and Durrleman, S}, title = {Interaction of sex and onset site on the disease trajectory of amyotrophic lateral sclerosis.}, journal = {Journal of neurology}, volume = {270}, number = {12}, pages = {5903-5912}, pmid = {37615751}, issn = {1432-1459}, support = {826421 (TVB-Cloud)//H2020 program/ ; ANR-10-IAIHU-06 (IHU ICM)//Agence Nationale de la Recherche/ ; ANR-19-P3IA-0001 (PRAIRIE 3IA Institute)//Agence Nationale de la Recherche/ ; ANR-19-JPW2-000 (E- DADS)//Agence Nationale de la Recherche/ ; }, mesh = {Male ; Humans ; Female ; *Amyotrophic Lateral Sclerosis ; Cross-Sectional Studies ; Disease Progression ; Survival Analysis ; Body Mass Index ; }, abstract = {BACKGROUND: Studies showed the impact of sex and onset site (spinal or bulbar) on disease onset and survival in ALS. However, they mainly result from cross-sectional or survival analysis, and the interaction of sex and onset site on the different proxies of disease trajectory has not been fully investigated.

METHODS: We selected all patients with repeated observations in the PRO-ACT database. We divided them into four groups depending on their sex and onset site. We estimated a multivariate disease progression model, named ALS Course Map, to investigate the combined temporal changes of the four sub-scores of the revised ALS functional rating scale (ALSFRSr), the forced vital capacity (FVC), and the body mass index (BMI). We then compared the progression rate, the estimated age at onset, and the relative progression of the outcomes across each group.

RESULTS: We included 1438 patients from the PRO-ACT database. They were 51% men with spinal onset, 12% men with bulbar onset, 26% women with spinal onset, and 11% women with bulbar onset. We showed a significant influence of both sex and onset site on the ALSFRSr progression. The BMI decreased 8.9 months earlier (95% CI [3.9, 13.8]) in women than men, after correction for the onset site. Among patients with bulbar onset, FVC was impaired 2.6 months earlier (95% CI [0.6, 4.6]) in women.

CONCLUSION: Using a multivariable disease modelling approach, we showed that sex and onset site are important drivers of the progression of motor function, BMI, and FVC decline.}, } @article {pmid37615238, year = {2023}, author = {Merriam, AB and Malone, JM and Hereward, JP and Gill, G and Preston, C}, title = {Point mutations including a novel Pro-197-Phe mutation confer cross-resistance to acetolactate synthase (ALS) inhibiting herbicides in Lactuca serriola in Australia.}, journal = {Pest management science}, volume = {79}, number = {12}, pages = {5333-5340}, doi = {10.1002/ps.7743}, pmid = {37615238}, issn = {1526-4998}, support = {//Grains Research and Development Corporation/ ; //Australian Government Research Training Program Scholarship/ ; }, mesh = {Humans ; Point Mutation ; *Acetolactate Synthase/genetics/metabolism ; *Herbicides/pharmacology ; Mutation ; Herbicide Resistance/genetics ; Phenylalanine/genetics ; Australia ; Proline/genetics ; Plant Proteins/genetics/metabolism ; }, abstract = {BACKGROUND: Control of prickly lettuce has become increasingly difficult for lentil growers in southern Australia because of widespread resistance to common herbicides, a lack of alternative herbicide options and the prolific production of highly mobile seed. This study aimed to quantify acetolactate synthase (ALS)-inhibiting herbicide resistance in the Mid North (MN) and Yorke Peninsula (YP) of South Australia, characterize the resistance mutations present and investigate population structure and gene flow in this species.

RESULTS: Resistance was identified in all populations tested, with average survival of 92% to chlorsulfuron and 95% to imazamox + imazapyr. Five different amino acid substitutions were identified at proline 197 of the ALS gene. There was no significant difference in the median lethal dose (LD50) between plants with these five different substitutions when treated with metsulfuron-methyl; however, the imidazolinone resistance level was higher in plants with a phenylalanine substitution and lower in plants with a serine. Population structure based on 701 single nucleotide polymorphisms and 271 individuals provided evidence for both independent evolution of the same mutation in different populations, as well as frequent short- to medium-distance dispersal accompanied by occasional long-distance dispersal events. The overall inbreeding coefficient (FIS) was calculated at 0.5174, indicating an intermediate level of outcrossing despite the cross-pollination experiment showing only low outcrossing. In the structure analyses, most individuals from YP were assigned to a single cluster, whereas most individuals from MN were assigned 50% to each of two clusters, indicating some genetic differences between these two regions, but also evidence for dispersal between them.

CONCLUSIONS: Use of imidazolinone herbicides has selected for mutations conferring higher levels of resistance, such as the Pro-197-Phe mutation, and resulted in further spread of resistance in this species. © 2023 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.}, } @article {pmid37614471, year = {2023}, author = {Bhattacharya, MRC}, title = {A nerve-wracking buzz: lessons from Drosophila models of peripheral neuropathy and axon degeneration.}, journal = {Frontiers in aging neuroscience}, volume = {15}, number = {}, pages = {1166146}, pmid = {37614471}, issn = {1663-4365}, support = {R01 NS105680/NS/NINDS NIH HHS/United States ; }, abstract = {The degeneration of axons and their terminals occurs following traumatic, toxic, or genetically-induced insults. Common molecular mechanisms unite these disparate triggers to execute a conserved nerve degeneration cascade. In this review, we will discuss how models of peripheral nerve injury and neuropathy in Drosophila have led the way in advancing molecular understanding of axon degeneration and nerve injury pathways. Both neuron-intrinsic as well as glial responses to injury will be highlighted. Finally, we will offer perspective on what additional questions should be answered to advance these discoveries toward clinical interventions for patients with neuropathy.}, } @article {pmid37614251, year = {2023}, author = {Hussein, S and Pingili, S and Makkena, VK and Jaramillo, AP and Awosusi, BL and Ayyub, J and Dabhi, KN and Gohil, NV and Tanveer, N and Hamid, P}, title = {The Impact of Serum Uric Acid on the Progression of Amyotrophic Lateral Sclerosis in Adults Aged 18 and Older: A Systematic Review.}, journal = {Cureus}, volume = {15}, number = {7}, pages = {e42312}, pmid = {37614251}, issn = {2168-8184}, abstract = {We have conducted this review to see if serum uric acid (UA) is associated with slowing amyotrophic lateral sclerosis (ALS) progression in adult patients who are at least 18 years old. Understanding the effects of this biomarker for future use is critical because of its easy accessibility. This systematic review paper examined five previous years of recent studies and reports, published in English and limited to human investigations from the Cochrane, PubMed, and Google Scholar databases. Using instruments for assessing the eligibility and quality of systematic and narrative reviews, we narrowed our search to 11 reports that show evidence of a positive association between high blood uric acid and the progression of ALS. However, this claim still needs confirmation by future studies to confirm that possibility. The results of this systematic review may provide a strong foundation for future studies on this biomarker, demonstrating the significance of blood uric acid levels in ALS and highlighting the necessity of using that biomarker to track the disease's progression.}, } @article {pmid37614226, year = {2023}, author = {Pickles, S and Zanetti Alepuz, D and Koike, Y and Yue, M and Tong, J and Liu, P and Zhou, Y and Jansen-West, K and Daughrity, LM and Song, Y and DeTure, M and Oskarsson, B and Graff-Radford, NR and Boeve, BF and Petersen, RC and Josephs, KA and Dickson, DW and Ward, ME and Dong, L and Prudencio, M and Cook, CN and Petrucelli, L}, title = {CRISPR interference to evaluate modifiers of C9ORF72-mediated toxicity in FTD.}, journal = {Frontiers in cell and developmental biology}, volume = {11}, number = {}, pages = {1251551}, pmid = {37614226}, issn = {2296-634X}, support = {R35 NS097273/NS/NINDS NIH HHS/United States ; R01 AG065219/AG/NIA NIH HHS/United States ; R01 AG063780/AG/NIA NIH HHS/United States ; RF1 AG062077/AG/NIA NIH HHS/United States ; P01 NS084974/NS/NINDS NIH HHS/United States ; R01 AG037491/AG/NIA NIH HHS/United States ; U54 NS123743/NS/NINDS NIH HHS/United States ; RF1 NS120992/NS/NINDS NIH HHS/United States ; }, abstract = {Treatments for neurodegenerative disease, including Frontotemporal dementia (FTD) and Amyotrophic lateral sclerosis (ALS), remain rather limited, underscoring the need for greater mechanistic insight and disease-relevant models. Our ability to develop novel disease models of genetic risk factors, disease modifiers, and other FTD/ALS-relevant targets is impeded by the significant amount of time and capital required to develop conventional knockout and transgenic mice. To overcome these limitations, we have generated a novel CRISPRi interference (CRISPRi) knockin mouse. CRISPRi uses a catalytically dead form of Cas9, fused to a transcriptional repressor to knockdown protein expression, following the introduction of single guide RNA against the gene of interest. To validate the utility of this model we have selected the TAR DNA binding protein (TDP-43) splicing target, stathmin-2 (STMN2). STMN2 RNA is downregulated in FTD/ALS due to loss of TDP-43 activity and STMN2 loss is suggested to play a role in ALS pathogenesis. The involvement of STMN2 loss of function in FTD has yet to be determined. We find that STMN2 protein levels in familial FTD cases are significantly reduced compared to controls, supporting that STMN2 depletion may be involved in the pathogenesis of FTD. Here, we provide proof-of-concept that we can simultaneously knock down Stmn2 and express the expanded repeat in the Chromosome 9 open reading frame 72 (C9ORF72) gene, successfully replicating features of C9-associated pathology. Of interest, depletion of Stmn2 had no effect on expression or deposition of dipeptide repeat proteins (DPRs), but significantly decreased the number of phosphorylated Tdp-43 (pTdp-43) inclusions. We submit that our novel CRISPRi mouse provides a versatile and rapid method to silence gene expression in vivo and propose this model will be useful to understand gene function in isolation or in the context of other neurodegenerative disease models.}, } @article {pmid37614106, year = {2023}, author = {Golini, E and Marinelli, S and Pisu, S and De Angelis, F and Vacca, V and Rava, A and Casola, I and Laurenzi, G and Rizzuto, E and Giuliani, A and Musarò, A and Dobrowolny, G and Mandillo, S}, title = {Wheel Running Adversely Affects Disease Onset and Neuromuscular Interplay in Amyotrophic Lateral Sclerosis Slow Progression Mouse Model.}, journal = {Current neurovascular research}, volume = {20}, number = {3}, pages = {362-376}, doi = {10.2174/1567202620666230823095922}, pmid = {37614106}, issn = {1875-5739}, mesh = {Male ; Animals ; Mice ; *Amyotrophic Lateral Sclerosis ; Motor Activity ; Disease Models, Animal ; Disease Progression ; }, abstract = {BACKGROUND: Physical activity in Amyotrophic Lateral Sclerosis (ALS) plays a controversial role. In some epidemiological studies, both recreational or professional sport exercise has been associated to an increased risk for ALS but the mechanisms underlying the effects of exercise have not been fully elucidated in either patients or animal models.

METHODS: To better reproduce the influence of this environmental factor in the pathogenesis of ALS, we exposed SOD1[G93A] low-copy male mice to multiple exercise sessions at asymptomatic and pre-symptomatic disease stages in an automated home-cage running-wheel system for about 3 months.

RESULTS: Repeated voluntary running negatively influenced disease progression by anticipating disease onset, impairing neuromuscular transmission, worsening neuromuscular decline, and exacerbating muscle atrophy. Muscle fibers and neuromuscular junctions (NMJ) as well as key molecular players of the nerve-muscle circuit were similarly affected.

CONCLUSION: It thus appears that excessive physical activity can be detrimental in predisposed individuals and these findings could model the increased risk of developing ALS in predisposed and specific professional athletes.}, } @article {pmid37614052, year = {2023}, author = {Oleinik, N and Albayram, O and Kassir, MF and Atilgan, FC and Walton, C and Karakaya, E and Kurtz, J and Alekseyenko, A and Alsudani, H and Sheridan, M and Szulc, ZM and Ogretmen, B}, title = {Alterations of lipid-mediated mitophagy result in aging-dependent sensorimotor defects.}, journal = {Aging cell}, volume = {22}, number = {10}, pages = {e13954}, pmid = {37614052}, issn = {1474-9726}, support = {I01 BX002466/BX/BLRD VA/United States ; R01 DE016572/DE/NIDCR NIH HHS/United States ; P20 GM148302/GM/NIGMS NIH HHS/United States ; CA203628/CA/NCI NIH HHS/United States ; R56 AG069769/AG/NIA NIH HHS/United States ; R01 CA214461/CA/NCI NIH HHS/United States ; }, mesh = {Mice ; Animals ; *Mitophagy ; *Malates ; Ceramides/metabolism ; Motor Neurons/metabolism ; Fumarates ; Ubiquitin-Protein Ligases ; }, abstract = {The metabolic consequences of mitophagy alterations due to age-related stress in healthy aging brains versus neurodegeneration remain unknown. Here, we demonstrate that ceramide synthase 1 (CerS1) is transported to the outer mitochondrial membrane by the p17/PERMIT transporter that recognizes mislocalized mitochondrial ribosomes (mitoribosomes) via 39-FLRN-42 residues, inducing ceramide-mediated mitophagy. P17/PERMIT-CerS1-mediated mitophagy attenuated the argininosuccinate/fumarate/malate axis and induced d-glucose and fructose accumulation in neurons in culture and brain tissues (primarily in the cerebellum) of wild-type mice in vivo. These metabolic changes in response to sodium-selenite were nullified in the cerebellum of CerS1to/to (catalytically inactive for C18-ceramide production CerS1 mutant), PARKIN-/- or p17/PERMIT-/- mice that have dysfunctional mitophagy. Whereas sodium selenite induced mitophagy in the cerebellum and improved motor-neuron deficits in aged wild-type mice, exogenous fumarate or malate prevented mitophagy. Attenuating ceramide-mediated mitophagy enhanced damaged mitochondria accumulation and age-dependent sensorimotor abnormalities in p17/PERMIT-/- mice. Reinstituting mitophagy using a ceramide analog drug with selenium conjugate, LCL768, restored mitophagy and reduced malate/fumarate metabolism, improving sensorimotor deficits in old p17/PERMIT-/- mice. Thus, these data describe the metabolic consequences of alterations to p17/PERMIT/ceramide-mediated mitophagy associated with the loss of mitochondrial quality control in neurons and provide therapeutic options to overcome age-dependent sensorimotor deficits and related disorders like amyotrophic lateral sclerosis (ALS).}, } @article {pmid37614020, year = {2024}, author = {Rotshild, V and Matok, I}, title = {Authors Reply to Comment on Rotshild et al's "The Risk for Prostate Cancer With Calcium Channel Blockers".}, journal = {The Annals of pharmacotherapy}, volume = {58}, number = {4}, pages = {443}, doi = {10.1177/10600280231185784}, pmid = {37614020}, issn = {1542-6270}, mesh = {Male ; Humans ; *Calcium Channel Blockers/adverse effects ; *Prostatic Neoplasms/drug therapy ; }, } @article {pmid37614019, year = {2024}, author = {Liao, KF and Hwang, BF and Liu, CS and Lai, SW}, title = {Comment on Rotshild et al's "The Risk for Prostate Cancer With Calcium Channel Blockers".}, journal = {The Annals of pharmacotherapy}, volume = {58}, number = {4}, pages = {441-442}, doi = {10.1177/10600280231185781}, pmid = {37614019}, issn = {1542-6270}, mesh = {Male ; Humans ; *Calcium Channel Blockers/adverse effects ; *Prostatic Neoplasms/drug therapy ; }, } @article {pmid37612833, year = {2023}, author = {Choi, SJ and Yoon, SH and Sung, JJ and Lee, JH}, title = {Association Between Fat Depletion and Prognosis of Amyotrophic Lateral Sclerosis: CT-Based Body Composition Analysis.}, journal = {Annals of neurology}, volume = {94}, number = {6}, pages = {1116-1125}, doi = {10.1002/ana.26775}, pmid = {37612833}, issn = {1531-8249}, support = {04-2021-2280//Seoul National University Hospital Research Fund/ ; }, mesh = {Male ; Female ; Humans ; Child, Preschool ; *Sarcopenia/diagnostic imaging/complications ; *Amyotrophic Lateral Sclerosis/complications/diagnostic imaging/pathology ; Retrospective Studies ; Creatinine ; Prognosis ; Muscle, Skeletal/pathology ; Body Composition ; Tomography, X-Ray Computed ; }, abstract = {OBJECTIVE: The purpose of this study was to present the results of our investigation of the prognostic value of adipopenia and sarcopenia in patients with amyotrophic lateral sclerosis (ALS).

METHODS: Consecutive patients with ALS with abdominal computed tomography (CT) were retrospectively identified at a single tertiary hospital between January 2010 and July 2021. Deep learning-based volumetric CT body composition analysis software was used to obtain abdominal waist fat volume, fat attenuation, and skeletal muscle area at the L3 level, then normalized to the fat volume index (FVI) and skeletal muscle index (SMI). Adipopenia and sarcopenia were defined as the sex-specific lowest quartile and SMI reference values, respectively. The associations of CT-derived body composition parameters with clinical variables, such as body mass index (BMI) and creatinine, were evaluated by Pearson correlation analyses, and associations with survival were assessed using the multivariable Cox regression analysis.

RESULTS: Eighty subjects (40 men, 65.5 ± 9.4 years of age) were investigated (median interval between disease onset and CT examination = 25 months). The mean BMI at the CT examination was 20.3 ± 4.3 kg/m[2] . The BMI showed a positive correlation with both FVI (R = 0.70, p < 0.001) and SMI (R = 0.63, p < 0.001), and the serum creatinine level was associated with SMI (R = 0.68, p < 0.001). After adjusting for sex, age, King's stage, BMI, creatinine, progression rate, and sarcopenia, adipopenia was associated with shorter survival (hazard ratio [HR] = 5.94, 95% confidence interval [CI] = 1.01, 35.0, p = 0.049). In a subgroup analysis for subjects with nutritional failure (stage 4a), the HR of adipopenia was 15.1 (95% CI = 2.45, 93.4, p = 0.003).

INTERPRETATION: Deep learning-based CT-derived adipopenia in patients with ALS is an independent poor prognostic factor for survival. ANN NEUROL 2023;94:1116-1125.}, } @article {pmid37612500, year = {2023}, author = {Willett, FR and Kunz, EM and Fan, C and Avansino, DT and Wilson, GH and Choi, EY and Kamdar, F and Glasser, MF and Hochberg, LR and Druckmann, S and Shenoy, KV and Henderson, JM}, title = {A high-performance speech neuroprosthesis.}, journal = {Nature}, volume = {620}, number = {7976}, pages = {1031-1036}, pmid = {37612500}, issn = {1476-4687}, support = {R01 MH060974/MH/NIMH NIH HHS/United States ; U01 DC017844/DC/NIDCD NIH HHS/United States ; U01 DC019430/DC/NIDCD NIH HHS/United States ; }, mesh = {Humans ; Amyotrophic Lateral Sclerosis/physiopathology/rehabilitation ; *Brain-Computer Interfaces ; Cerebral Cortex/physiology ; Microelectrodes ; *Paralysis/physiopathology/rehabilitation ; *Speech ; Vocabulary ; *Neural Prostheses ; }, abstract = {Speech brain-computer interfaces (BCIs) have the potential to restore rapid communication to people with paralysis by decoding neural activity evoked by attempted speech into text[1,2] or sound[3,4]. Early demonstrations, although promising, have not yet achieved accuracies sufficiently high for communication of unconstrained sentences from a large vocabulary[1-7]. Here we demonstrate a speech-to-text BCI that records spiking activity from intracortical microelectrode arrays. Enabled by these high-resolution recordings, our study participant-who can no longer speak intelligibly owing to amyotrophic lateral sclerosis-achieved a 9.1% word error rate on a 50-word vocabulary (2.7 times fewer errors than the previous state-of-the-art speech BCI[2]) and a 23.8% word error rate on a 125,000-word vocabulary (the first successful demonstration, to our knowledge, of large-vocabulary decoding). Our participant's attempted speech was decoded at 62 words per minute, which is 3.4 times as fast as the previous record[8] and begins to approach the speed of natural conversation (160 words per minute[9]). Finally, we highlight two aspects of the neural code for speech that are encouraging for speech BCIs: spatially intermixed tuning to speech articulators that makes accurate decoding possible from only a small region of cortex, and a detailed articulatory representation of phonemes that persists years after paralysis. These results show a feasible path forward for restoring rapid communication to people with paralysis who can no longer speak.}, } @article {pmid37612427, year = {2023}, author = {Cheng, J and Ho, WK and Wu, BT and Liu, HP and Lin, WY}, title = {miRNA profiling as a complementary diagnostic tool for amyotrophic lateral sclerosis.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {13805}, pmid = {37612427}, issn = {2045-2322}, mesh = {*Amyotrophic Lateral Sclerosis/diagnosis ; Humans ; *MicroRNAs/analysis/genetics ; Gene Expression Profiling ; Machine Learning ; }, abstract = {Amyotrophic lateral sclerosis (ALS), the most prevalent motor neuron disease characterized by its complex genetic structure, lacks a single diagnostic test capable of providing a conclusive diagnosis. In order to demonstrate the potential for genetic diagnosis and shed light on the pathogenic role of miRNAs in ALS, we developed an ALS diagnostic rule by training the model using 80% of a miRNA profiling dataset consisting of 253 ALS samples and 103 control samples. Subsequently, we validated the diagnostic rule using the remaining 20% of unseen samples. The diagnostic rule we developed includes miR-205-5p, miR-206, miR-376a-5p, miR-412-5p, miR-3927-3p, miR-4701-3p, miR-6763-5p, and miR-6801-3p. Remarkably, the rule achieved an 82% true positive rate and a 73% true negative rate when predicting the unseen samples. Furthermore, the identified miRNAs target 21 genes in the PI3K-Akt pathway and 27 genes in the ALS pathway, including notable genes such as BCL2, NEFH, and OPTN. We propose that miRNA profiling may serve as a complementary diagnostic tool to supplement the clinical presentation and aid in the early recognition of ALS.}, } @article {pmid37612295, year = {2023}, author = {Kokalj, Ž and Džeroski, S and Šprajc, I and Štajdohar, J and Draksler, A and Somrak, M}, title = {Machine learning-ready remote sensing data for Maya archaeology.}, journal = {Scientific data}, volume = {10}, number = {1}, pages = {558}, pmid = {37612295}, issn = {2052-4463}, support = {4000130508/20/I-NB//European Space Agency (ESA)/ ; P2-0406//Javna Agencija za Raziskovalno Dejavnost RS (Slovenian Research Agency)/ ; J6-7085//Javna Agencija za Raziskovalno Dejavnost RS (Slovenian Research Agency)/ ; P6-0079//Javna Agencija za Raziskovalno Dejavnost RS (Slovenian Research Agency)/ ; J6-7085//Javna Agencija za Raziskovalno Dejavnost RS (Slovenian Research Agency)/ ; J6-7085//Javna Agencija za Raziskovalno Dejavnost RS (Slovenian Research Agency)/ ; J6-7085//Javna Agencija za Raziskovalno Dejavnost RS (Slovenian Research Agency)/ ; P2-0406//Javna Agencija za Raziskovalno Dejavnost RS (Slovenian Research Agency)/ ; }, abstract = {In our study, we set out to collect a multimodal annotated dataset for remote sensing of Maya archaeology, that is suitable for deep learning. The dataset covers the area around Chactún, one of the largest ancient Maya urban centres in the central Yucatán Peninsula. The dataset includes five types of data records: raster visualisations and canopy height model from airborne laser scanning (ALS) data, Sentinel-1 and Sentinel-2 satellite data, and manual data annotations. The manual annotations (used as binary masks) represent three different types of ancient Maya structures (class labels: buildings, platforms, and aguadas - artificial reservoirs) within the study area, their exact locations, and boundaries. The dataset is ready for use with machine learning, including convolutional neural networks (CNNs) for object recognition, object localization (detection), and semantic segmentation. We would like to provide this dataset to help more research teams develop their own computer vision models for investigations of Maya archaeology or improve existing ones.}, } @article {pmid37611905, year = {2024}, author = {Huang, Q and Wang, Y and Chen, S and Liang, F}, title = {Glycometabolic Reprogramming of Microglia in Neurodegenerative Diseases: Insights from Neuroinflammation.}, journal = {Aging and disease}, volume = {15}, number = {3}, pages = {1155-1175}, pmid = {37611905}, issn = {2152-5250}, mesh = {*Microglia/metabolism ; Humans ; *Neurodegenerative Diseases/metabolism/pathology ; *Glucose/metabolism ; Neuroinflammatory Diseases/metabolism/immunology ; Animals ; }, abstract = {Neurodegenerative diseases (ND) are conditions defined by progressive deterioration of the structure and function of the nervous system. Some major examples include Alzheimer's disease (AD), Parkinson's disease (PD), and Amyotrophic lateral sclerosis (ALS). These diseases lead to various dysfunctions, like impaired cognition, memory, and movement. Chronic neuroinflammation may underlie numerous neurodegenerative disorders. Microglia, an important immunocell in the brain, plays a vital role in defending against neuroinflammation. When exposed to different stimuli, microglia are activated and assume different phenotypes, participating in immune regulation of the nervous system and maintaining tissue homeostasis. The immunological activity of activated microglia is affected by glucose metabolic alterations. However, in the context of chronic neuroinflammation, specific alterations of microglial glucose metabolism and their mechanisms of action remain unclear. Thus, in this paper, we review the glycometabolic reprogramming of microglia in ND. The key molecular targets and main metabolic pathways are the focus of this research. Additionally, this study explores the mechanisms underlying microglial glucose metabolism reprogramming in ND and offers an analysis of the most recent therapeutic advancements. The ultimate aim is to provide insights into the development of potential treatments for ND.}, } @article {pmid37611832, year = {2023}, author = {González-Torralva, F and Norsworthy, JK}, title = {Quizalofop resistance in weedy rice (Oryza sativa L.) is mainly conferred by an Ile1781Leu mutation.}, journal = {Plant science : an international journal of experimental plant biology}, volume = {336}, number = {}, pages = {111838}, doi = {10.1016/j.plantsci.2023.111838}, pmid = {37611832}, issn = {1873-2259}, mesh = {*Oryza/genetics ; Herbicide Resistance/genetics ; Mutation ; Plant Weeds/genetics ; *Herbicides/pharmacology ; }, abstract = {Weedy rice (Oryza sativa L.) is an economically important weed species in rice (Oryza sativa L.) cropping systems. Two weedy rice samples (acc7 and acc8) suspected to be resistant to quizalofop-ethyl (quizalofop) were collected in Arkansas. In this research, susceptibility to quizalofop and resistance mechanisms have been explored. Dose-response assays displayed a resistance index of 42- and 58-fold for the acc7 and acc8, respectively. Experiments with metabolism inhibitors demonstrated that NBD-Cl (4-chloro-7-nitrobenzofurazan) increased quizalofop efficacy slightly in acc8, whereas malathion did not improve effectiveness in resistant samples. Sequencing of the ACCase gene displayed an Ile1781Leu substitution in the resistant samples, like the mutation present in Provisia™ rice. In addition, an allele-specific PCR was developed to genotype the Ile1781Leu mutation. The gene copy number of ACCase showed similar values among samples. In the resistant plants, a KASP (Kompetitive Allele Specific PCR) assay to detect the ALS[S653D] (acetolactate synthase) and HIS1 (HPPD Inhibitor Sensitive 1) traits revealed that 37.5% of plants carried the ALS[S653D] trait, whereas 25% showed the HIS1 allele. In summary, a target-site mutation is the main resistance mechanism to quizalofop in weedy rice. Results also suggest the presence of herbicide metabolism (a non-target site resistance mechanism) mediated by glutathione-S-transferases (GSTs) in one resistant sample.}, } @article {pmid37610866, year = {2023}, author = {Kołodziej, D and Sobczak, Ł and Łączkowski, KZ}, title = {New opportunities for treatment and prevention of neurodegenerative diseases with PTP1B inhibitors.}, journal = {Future medicinal chemistry}, volume = {15}, number = {16}, pages = {1443-1447}, doi = {10.4155/fmc-2023-0187}, pmid = {37610866}, issn = {1756-8927}, mesh = {Humans ; *Neurodegenerative Diseases/drug therapy/prevention & control ; *Alzheimer Disease ; *Parkinson Disease ; *Amyotrophic Lateral Sclerosis ; }, } @article {pmid37610446, year = {2023}, author = {Bombaci, A and Lupica, A and Pozzi, FE and Remoli, G and Manera, U and Di Stefano, V}, title = {Sensory neuropathy in amyotrophic lateral sclerosis: a systematic review.}, journal = {Journal of neurology}, volume = {270}, number = {12}, pages = {5677-5691}, pmid = {37610446}, issn = {1432-1459}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/complications/diagnosis/epidemiology ; *Neurodegenerative Diseases ; Quality of Life ; Motor Neurons/physiology ; Electromyography ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the degeneration of both upper and lower motoneurons, leading to motor and non-motor symptoms. Recent evidence suggests that ALS is indeed a multisystem disorder, associated with cognitive impairment, dysautonomia, pain and fatigue, excess of secretions, and sensory symptoms. To evaluate whether sensory neuropathy could broaden its spectrum, we systematically reviewed its presence and characteristics in ALS, extracting data on epidemiological, clinical, neurophysiological, neuropathological, and genetic features. Sensory neuropathy can be found in up to 20% of ALS patients, affecting both large and small fibers, although there is a great heterogeneity related to different techniques used for its detection (electromyography vs skin biopsy vs nerve biopsy). Moreover, the association between CIDP-like neuropathy and ALS needs to be better explored, although it could be interpreted as part of the neuroinflammatory process in the latter disease. Sensory neuropathy in ALS may be associated with a spinal onset and might be more frequent in SOD1 patients. Moreover, it seems mutually exclusive with cognitive impairment. No associations with sex and other genetic mutation were observed. All these data in the literature reveal the importance of actively looking for sensory neuropathy in ALS patients, and suggest including sensory neuropathy among ALS non-motor features, as it may explain sensory symptoms frequently reported throughout the course of the disease. Its early identification could help avoid diagnostic delays and improve patients' treatment and quality of life.}, } @article {pmid37609280, year = {2023}, author = {Read, TA and Cisterna, BA and Skruber, K and Ahmadieh, S and Lindamood, HL and Vitriol, JA and Shi, Y and Lefebvre, AEYT and Black, JB and Butler, MT and Bear, JE and Cherezova, A and Ilatovskaya, DV and Weintraub, NL and Vitriol, EA}, title = {The actin binding protein profilin 1 is critical for mitochondria function.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {37609280}, issn = {2692-8205}, support = {R35 GM137959/GM/NIGMS NIH HHS/United States ; }, abstract = {Profilin 1 (PFN1) is an actin binding protein that is vital for the polymerization of monomeric actin into filaments. Here we screened knockout cells for novel functions of PFN1 and discovered that mitophagy, a type of selective autophagy that removes defective or damaged mitochondria from the cell, was significantly upregulated in the absence of PFN1. Despite successful autophagosome formation and fusion with the lysosome, and activation of additional mitochondrial quality control pathways, PFN1 knockout cells still accumulate damaged, dysfunctional mitochondria. Subsequent imaging and functional assays showed that loss of PFN1 significantly affects mitochondria morphology, dynamics, and respiration. Further experiments revealed that PFN1 is located to the mitochondria matrix and is likely regulating mitochondria function from within rather than through polymerizing actin at the mitochondria surface. Finally, PFN1 mutants associated with amyotrophic lateral sclerosis (ALS) fail to rescue PFN1 knockout mitochondrial phenotypes and form aggregates within mitochondria, further perturbing them. Together, these results suggest a novel function for PFN1 in regulating mitochondria and identify a potential pathogenic mechanism of ALS-linked PFN1 variants.}, } @article {pmid37609205, year = {2023}, author = {Shen, T and Vogel, JW and Duda, J and Phillips, JS and Cook, PA and Gee, J and Elman, L and Quinn, C and Amado, DA and Baer, M and Massimo, L and Grossman, M and Irwin, DJ and McMillan, CT}, title = {Novel data-driven subtypes and stages of brain atrophy in the ALS-FTD spectrum.}, journal = {Research square}, volume = {}, number = {}, pages = {}, pmid = {37609205}, issn = {2693-5015}, support = {T32 MH019112/MH/NIMH NIH HHS/United States ; P01 AG066597/AG/NIA NIH HHS/United States ; P30 AG072979/AG/NIA NIH HHS/United States ; R01 AG054519/AG/NIA NIH HHS/United States ; K01 AG061277/AG/NIA NIH HHS/United States ; R01 NS109260/NS/NINDS NIH HHS/United States ; }, abstract = {BACKGROUND: TDP-43 proteinopathies represents a spectrum of neurological disorders, anchored clinically on either end by amyotrophic lateral sclerosis (ALS) and frontotemporal degeneration (FTD). The ALS-FTD spectrum exhibits a diverse range of clinical presentations with overlapping phenotypes, highlighting its heterogeneity. This study aimed to use disease progression modeling to identify novel data-driven spatial and temporal subtypes of brain atrophy and its progression in the ALS-FTD spectrum.

METHODS: We used a data-driven procedure to identify 13 anatomic clusters of brain volumes for 57 behavioral variant FTD (bvFTD; with either autopsy-confirmed TDP-43 or TDP-43 proteinopathy-associated genetic variants), 103 ALS, and 47 ALS-FTD patients with likely TDP-43. A Subtype and Stage Inference (SuStaIn) model was trained to identify subtypes of individuals along the ALS-FTD spectrum with distinct brain atrophy patterns, and we related subtypes and stages to clinical, genetic, and neuropathological features of disease.

RESULTS: SuStaIn identified three novel subtypes: two disease subtypes with predominant brain atrophy either in prefrontal/somatomotor regions or limbic-related regions, and a normal-appearing group without obvious brain atrophy. The Limbic-predominant subtype tended to present with more impaired cognition, higher frequencies of pathogenic variants in TBK1 and TARDBP genes, and a higher proportion of TDP-43 type B, E and C. In contrast, the Prefrontal/Somatomotor-predominant subtype had higher frequencies of pathogenic variants in C9orf72 and GRN genes and higher proportion of TDP-43 type A. The normal-appearing brain group showed higher frequency of ALS relative to ALS-FTD and bvFTD patients, higher cognitive capacity, higher proportion of lower motor neuron onset, milder motor symptoms, and lower frequencies of genetic pathogenic variants. Overall SuStaIn stages also correlated with evidence for clinical progression including longer disease duration, higher King's stage, and cognitive decline. Additionally, SuStaIn stages differed across clinical phenotypes, genotypes and types of TDP-43 pathology.

CONCLUSIONS: Our findings suggest distinct neurodegenerative subtypes of disease along the ALS-FTD spectrum that can be identified in vivo, each with distinct brain atrophy, clinical, genetic and pathological patterns.}, } @article {pmid37608584, year = {2023}, author = {Solovyev, N and Lucio, M and Mandrioli, J and Forcisi, S and Kanawati, B and Uhl, J and Vinceti, M and Schmitt-Kopplin, P and Michalke, B}, title = {Interplay of Metallome and Metabolome in Amyotrophic Lateral Sclerosis: A Study on Cerebrospinal Fluid of Patients Carrying Disease-Related Gene Mutations.}, journal = {ACS chemical neuroscience}, volume = {14}, number = {17}, pages = {3035-3046}, pmid = {37608584}, issn = {1948-7193}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis ; Copper ; Manganese ; *Neurodegenerative Diseases ; Metabolome ; Mutation ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a lethal progressive neurodegenerative disease, characterized by a loss of function of upper and lower motor neurons. This study aimed to explore probable pathological alterations occurring in individuals with ALS compared to neurologically healthy controls through the analysis of cerebrospinal fluid (CSF), a medium, which directly interacts with brain parenchyma. A total of 7 ALS patients with disease-associated mutations (ATXN2, C9ORF72, FUS, SOD1, and TARDBP) and 13 controls were included in the study. Multiple analytical approaches were employed, including metabolomic and metallomics profiling, as well as genetic screening, using CSF samples obtained from the brain compartment. Data analysis involved the application of multivariate statistical methods. Advanced hyphenated selenium and redox metal (iron, copper, and manganese) speciation techniques and nontargeted Fourier transform ion cyclotron resonance mass spectrometry-based metabolomics were used for data acquisition. Nontargeted metabolomics showed reduced steroids, including sex hormones; additionally, copper and manganese species were found to be the most relevant features for ALS patients. This indicates a potential alteration of sex hormone pathways in the ALS-affected brain, as reflected in the CSF.}, } @article {pmid37608352, year = {2023}, author = {Bjorklund, GR and Wong, J and Brafman, D and Bowser, R and Stabenfeldt, SE}, title = {Traumatic brain injury induces TDP-43 mislocalization and neurodegenerative effects in tissue distal to the primary injury site in a non-transgenic mouse.}, journal = {Acta neuropathologica communications}, volume = {11}, number = {1}, pages = {137}, pmid = {37608352}, issn = {2051-5960}, support = {R01 NS116657/NS/NINDS NIH HHS/United States ; R03 NS122018/NS/NINDS NIH HHS/United States ; }, mesh = {Mice ; Animals ; *Amyotrophic Lateral Sclerosis ; *Frontotemporal Dementia ; *Brain Injuries, Traumatic/complications ; Brain ; *Alzheimer Disease ; DNA-Binding Proteins/genetics ; *Pick Disease of the Brain ; }, abstract = {Traumatic brain injury (TBI) initiates tissue and cellular damage to the brain that is immediately followed by secondary injury sequalae with delayed and continual damage. This secondary damage includes pathological processes that may contribute to chronic neurodegeneration and permanent functional and cognitive deficits. TBI is also associated with an increased risk of developing neurodegenerative diseases such as Alzheimer's disease (AD), frontotemporal dementia (FTD), and amyotrophic lateral sclerosis (ALS) as indicated by shared pathological features. For example, abnormalities in the TAR DNA-binding Protein 43 (TDP-43) that includes cytoplasmic mislocalization, cytosolic aggregation, and an increase in phosphorylation and ubiquitination are seen in up to 50% of FTD cases, up to 70% of AD cases, and is considered a hallmark pathology of ALS occurring in > 97% of cases. Yet the prevalence of TDP-43 pathology post-TBI has yet to be fully characterized. Here, we employed a non-transgenic murine controlled cortical injury model of TBI and observed injury-induced hallmark TDP-43 pathologies in brain and spinal cord tissue distal to the primary injury site and did not include the focally damaged tissue within the primary cortical injury site. Analysis revealed a temporal-dependent and significant increase in neuronal TDP-43 mislocalization in the cortical forebrain rostral to and distant from the primary injury site up to 180 days post injury (DPI). TDP-43 mislocalization was also detected in neurons located in the ventral horns of the cervical spinal cord following a TBI. Moreover, a cortical layer-dependent affect was identified, increasing from superficial to deeper cortical layers over time from 7 DPI up to 180 DPI. Lastly, RNAseq analysis confirmed an injury-induced misregulation of several key biological processes implicated in neurons that increased over time. Collectively, this study demonstrates a connection between a single moderate TBI event and chronic neurodegenerative processes that are not limited to the primary injury site and broadly distributed throughout the cortex and corticospinal tract.}, } @article {pmid37608094, year = {2023}, author = {Mlynárik, V}, title = {Amyotrophic lateral sclerosis and the upper motor neurons: we do need more than meets the eye.}, journal = {European radiology}, volume = {33}, number = {11}, pages = {7675-7676}, pmid = {37608094}, issn = {1432-1084}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis ; *Motor Cortex ; Motor Neurons ; }, } @article {pmid37608081, year = {2023}, author = {Chattopadhyay, S and Do, NP and Flower, DR and Chattopadhyay, AK}, title = {Extracting prime protein targets as possible drug candidates: machine learning evaluation.}, journal = {Medical & biological engineering & computing}, volume = {61}, number = {11}, pages = {3035-3048}, pmid = {37608081}, issn = {1741-0444}, support = {76/QD-BGDDT//National Foundation for Science and Technology Development/ ; }, mesh = {Molecular Docking Simulation ; *Drug Design ; *Proteins ; Algorithms ; Machine Learning ; }, abstract = {Extracting "high ranking" or "prime protein targets" (PPTs) as potent MRSA drug candidates from a given set of ligands is a key challenge in efficient molecular docking. This study combines protein-versus-ligand matching molecular docking (MD) data extracted from 10 independent molecular docking (MD) evaluations - ADFR, DOCK, Gemdock, Ledock, Plants, Psovina, Quickvina2, smina, vina, and vinaxb to identify top MRSA drug candidates. Twenty-nine active protein targets (APT) from the enhanced DUD-E repository (http://DUD-E.decoys.org) are matched against 1040 ligands using "forward modeling" machine learning for initial "data mining and modeling" (DDM) to extract PPTs and the corresponding high affinity ligands (HALs). K-means clustering (KMC) is then performed on 400 ligands matched against 29 PTs, with each cluster accommodating HALs, and the corresponding PPTs. Performance of KMC is then validated against randomly chosen head, tail, and middle active ligands (ALs). KMC outcomes have been validated against two other clustering methods, namely, Gaussian mixture model (GMM) and density based spatial clustering of applications with noise (DBSCAN). While GMM shows similar results as with KMC, DBSCAN has failed to yield more than one cluster and handle the noise (outliers), thus affirming the choice of KMC or GMM. Databases obtained from ADFR to mine PPTs are then ranked according to the number of the corresponding HAL-PPT combinations (HPC) inside the derived clusters, an approach called "reverse modeling" (RM). From the set of 29 PTs studied, RM predicts high fidelity of 5 PPTs (17%) that bind with 76 out of 400, i.e., 19% ligands leading to a prediction of next-generation MRSA drug candidates: PPT2 (average HPC is 41.1%) is the top choice, followed by PPT14 (average HPC 25.46%), and then PPT15 (average HPC 23.12%). This algorithm can be generically implemented irrespective of pathogenic forms and is particularly effective for sparse data.}, } @article {pmid37607754, year = {2023}, author = {Cluse, F and Hermier, M and Demarquay, G and Rogemond, V and Mallaret, M and Svahn, J and Pegat, A and Honnorat, J and Bernard, E}, title = {Trigeminal Nerve Involvement in Bulbar-Onset Anti-IgLON5 Disease.}, journal = {Neurology(R) neuroimmunology & neuroinflammation}, volume = {10}, number = {6}, pages = {}, pmid = {37607754}, issn = {2332-7812}, mesh = {*Amyotrophic Lateral Sclerosis ; *Trigeminal Nerve Diseases ; Gadolinium ; Trigeminal Nerve ; Humans ; Contrast Media ; Hashimoto Disease ; Encephalitis ; }, abstract = {OBJECTIVES: Anti-IgLON5 disease (IgLON5-D) may present with a bulbar-onset motor neuron disease-like phenotype, mimicking bulbar-onset amyotrophic lateral sclerosis. Recognition of their distinctive clinical and paraclinical features may help for differential diagnosis. We report 2 cases of atypical trigeminal neuropathy in bulbar-onset IgLON5-D.

METHODS: Trigeminal nerve involvement was assessed using comprehensive clinical, laboratory, electrophysiologic, and MRI workup.

RESULTS: Both patients were referred for progressive dysphagia, sialorrhea, and hoarseness. They were treated with bilevel positive airway pressure for nocturnal hypoventilation. Patient 1 complained of continuous facial burning pain with allodynia, exacerbated by mastication and prolonged speech. Patient 2 reported no facial pain. Anti-IgLON5 autoantibodies (IgLON5-Abs) were positive in serum for both patients and CSF for patient 1. Cerebral MRI revealed bilateral T2 fluid-attenuated inversion recovery (FLAIR) hyperintensity and enlargement of trigeminal nerves without gadolinium enhancement in both patients. Needle myography showed fasciculations in masseter muscles. Blink-reflex study confirmed bilateral trigeminal neuropathy only in patient 2. Cortical laser-evoked potentials showed a bilateral small-fiber dysfunction in the trigeminal nerve ophthalmic branch in patient 1.

DISCUSSION: In case of progressive atypical bulbar symptoms, the presence of a trigeminal neuropathy or trigeminal nerve abnormalities on MRI should encourage the testing of IgLON5-Abs in serum and CSF.}, } @article {pmid37607386, year = {2023}, author = {Rong, P and Taylor, A}, title = {A Vowel-Centric View Toward Characterizing Temporal Organization of Motor Speech Activities in Neurologically Impaired and Healthy Speakers.}, journal = {Journal of speech, language, and hearing research : JSLHR}, volume = {66}, number = {10}, pages = {3697-3720}, doi = {10.1044/2023_JSLHR-23-00129}, pmid = {37607386}, issn = {1558-9102}, mesh = {Humans ; *Speech ; *Amyotrophic Lateral Sclerosis/complications ; Speech Acoustics ; Speech Disorders ; Speech Production Measurement ; Speech Intelligibility ; }, abstract = {PURPOSE: This study tested the hypotheses that (a) motor speech activities are temporally organized around the nuclei into vowel-centric units that hold both stability and flexibility and (b) such temporal organization is impacted by motor speech impairment.

METHOD: Thirteen individuals with amyotrophic lateral sclerosis and 10 healthy controls read a sentence 3 times at each of the following rates: habitual, fast, and slow. Articulatory gestures and phonatory event were assessed in two vowel-centric units, as operationally defined within and across the boundaries of two target words-cat and must-to accommodate common coda omission and coarticulation. Twelve absolute and relative timing measures centering on the nucleus were derived to characterize the temporal organization of each unit. These measures were evaluated in terms of (a) their relations with global duration across rate conditions and (b) between-groups differences for the habitual rate condition.

RESULTS: Both vowel-centric units remained stable in relative timing between the articulatory gestures approaching and moving away from the nucleus across rate conditions. Relative timing between the articulatory gestures and phonatory event at smaller temporal granularities varied with global duration, but in different ways for neurologically impaired and healthy speakers. Disease impacts on relative timing were only detected across word boundaries. All absolute timing measures revealed consistent temporal scaling effects and disease-related prolongations.

CONCLUSIONS: The findings provide preliminary support for vowel-centric temporal organization of motor speech activities. Such temporal organization holds some extent of both stability and flexibility, which may facilitate the parsing of syllabic events during auditory processing, while accommodating task-specific suprasegmental variations. The timing impairments in amyotrophic lateral sclerosis are likely attributed to the disease-imposed dynamic constraints, reducing the entrainment of the related motor speech activities to the underlying linguistic elements. These findings have potential implications in guiding the assessment and management of temporal speech deficits in ALS.}, } @article {pmid37607205, year = {2023}, author = {Keifer, OP and Gutierrez, J and Butt, MT and Cramer, SD and Bartus, R and Tansey, M and Deaver, D and Betourne, A and Boulis, NM}, title = {Spinal cord and brain concentrations of riluzole after oral and intrathecal administration: A potential new treatment route for amyotrophic lateral sclerosis.}, journal = {PloS one}, volume = {18}, number = {8}, pages = {e0277718}, pmid = {37607205}, issn = {1932-6203}, mesh = {Humans ; Animals ; Dogs ; *Amyotrophic Lateral Sclerosis/drug therapy ; Riluzole/therapeutic use ; Brain ; Administration, Oral ; *Drug-Related Side Effects and Adverse Reactions ; }, abstract = {Riluzole is the only treatment known to improve survival in patients with Amyotrophic Lateral Sclerosis (ALS). However, oral riluzole efficacy is modest at best, further it is known to have large inter-individual variability of serum concentration and clearance, is formulated as an oral drug in a patient population plagued with dysphagia, and has known systemic side-effects like asthenia (limiting patient compliance) and elevated liver enzymes. In this context, we postulated that continuous intrathecal (IT) infusion of low doses of riluzole could provide consistent elevations of the drug spinal cord (SC) concentrations at or above those achieved with oral dosing, without increasing the risk for adverse events associated with systemic drug exposure or off-target side effects in the brain. We developed a formulation of riluzole for IT delivery and conducted our studies in purpose-bred hound dogs. Our non-GLP studies revealed that IT infusion alone was able to increase SC concentrations above those provided by oral administration, without increasing plasma concentrations. We then conducted two GLP studies that combined IT infusion with oral administration at human equivalent dose, to evaluate SC and brain concentrations of riluzole along with assessments of safety and tolerability. In the 6-week study, the highest IT dose (0.2 mg/hr) was well tolerated by the animals and increased SC concentrations above those achieved with oral riluzole alone, without increasing brain concentrations. In the 6-month study, the highest dose tested (0.4 mg/hr) was not tolerated and yielded SC significantly above those achieved in all previous studies. Our data show the feasibility and safety profile of continuous IT riluzole delivery to the spinal cord, without concurrent elevated liver enzymes, and minimal brain concentrations creating another potential therapeutic route of delivery to be used in isolation or in combination with other therapeutics."}, } @article {pmid37606662, year = {2023}, author = {Lo Russo, F and Contarino, VE and Conte, G and Morelli, C and Trogu, F and Casale, S and Sbaraini, S and Caschera, L and Genovese, V and Liu, C and Cinnante, CM and Silani, V and Triulzi, FM}, title = {Amyotrophic lateral sclerosis with upper motor neuron predominance: diagnostic accuracy of qualitative and quantitative susceptibility metrics in the precentral gyrus.}, journal = {European radiology}, volume = {33}, number = {11}, pages = {7677-7685}, pmid = {37606662}, issn = {1432-1084}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnostic imaging ; *Motor Cortex/diagnostic imaging ; Retrospective Studies ; Motor Neurons ; *Motor Neuron Disease/diagnostic imaging ; Magnetic Resonance Imaging/methods ; }, abstract = {OBJECTIVE: The study aims at comparing the diagnostic accuracy of qualitative and quantitative assessment of the susceptibility in the precentral gyrus in detecting amyotrophic lateral sclerosis (ALS) with predominance of upper motor neuron (UMN) impairment.

METHODS: We retrospectively collected clinical and 3T MRI data of 47 ALS patients, of whom 12 with UMN predominance (UMN-ALS). We further enrolled 23 healthy controls (HC) and 15 ALS Mimics (ALS-Mim). The Motor Cortex Susceptibility (MCS) score was qualitatively assessed on the susceptibility-weighted images (SWI) and automatic metrics were extracted from the quantitative susceptibility mapping (QSM) in the precentral gyrus. MCS scores and QSM-based metrics were tested for correlation, and ROC analyses.

RESULTS: The correlation of MCS score and susceptibility skewness was significant (Rho = 0.55, p < 0.001). The susceptibility SD showed an AUC of 0.809 with a specificity and positive predictive value of 100% in differentiating ALS and ALS Mim versus HC, significantly higher than MCS (Z = -3.384, p-value = 0.00071). The susceptibility skewness value of -0.017 showed specificity of 92.3% and predictive positive value of 91.7% in differentiating UMN-ALS versus ALS mimics, even if the performance was not significantly better than MCS (Z = 0.81, p = 0.21).

CONCLUSION: The MCS and susceptibility skewness of the precentral gyrus show high diagnostic accuracy in differentiating UMN-ALS from ALS-mimics subjects. The quantitative assessment might be preferred being an automatic measure unbiased by the reader.

CLINICAL RELEVANCE STATEMENT: The clinical diagnostic evaluation of ALS patients might benefit from the qualitative and/or quantitative assessment of the susceptibility in the precentral gyrus as imaging marker of upper motor neuron predominance.

KEY POINTS: • Amyotrophic lateral sclerosis diagnostic work-up lacks biomarkers able to identify upper motor neuron involvement. • Susceptibility-weighted imaging/quantitative susceptibility mapping-based measures showed good diagnostic accuracy in discriminating amyotrophic lateral sclerosis with predominant upper motor neuron impairment from patients with suspected motor neuron disorder. • Susceptibility-weighted imaging/quantitative susceptibility mapping-based assessment of the magnetic susceptibility provides a diagnostic marker for amyotrophic lateral sclerosis with upper motor neuron predominance.}, } @article {pmid37606396, year = {2023}, author = {Shirai, R and Cho, M and Isogai, M and Fukatsu, S and Okabe, M and Okawa, M and Miyamoto, Y and Torii, T and Yamauchi, J}, title = {FTD/ALS Type 7-Associated Thr104Asn Mutation of CHMP2B Blunts Neuronal Process Elongation, and Is Recovered by Knockdown of Arf4, the Golgi Stress Regulator.}, journal = {Neurology international}, volume = {15}, number = {3}, pages = {980-993}, pmid = {37606396}, issn = {2035-8385}, abstract = {Frontotemporal dementia and/or amyotrophic lateral sclerosis type 7 (FTD/ALS7) is an autosomal dominant neurodegenerative disorder characterized by the onset of FTD and/or ALS, mainly in adulthood. Patients with some types of mutations, including the Thr104Asn (T104N) mutation of charged multivesicular body protein 2B (CHMP2B), have predominantly ALS phenotypes, whereas patients with other mutations have predominantly FTD phenotypes. A few mutations result in patients having both phenotypes approximately equally; however, the reason why phenotypes differ depending on the position of the mutation is unknown. CHMP2B comprises one part of the endosomal sorting complexes required for transport (ESCRT), specifically ESCRT-III, in the cytoplasm. We describe here, for the first time, that CHMP2B with the T104N mutation inhibits neuronal process elongation in the N1E-115 cell line, a model line undergoing neuronal differentiation. This inhibitory phenotype was accompanied by changes in marker protein expression. Of note, CHMP2B with the T104N mutation, but not the wild-type form, was preferentially accumulated in the Golgi body. Of the four major Golgi stress signaling pathways currently known, the pathway through Arf4, the small GTPase, was specifically upregulated in cells expressing CHMP2B with the T104N mutation. Conversely, knockdown of Arf4 with the cognate small interfering (si)RNA recovered the neuronal process elongation inhibited by the T104N mutation. These results suggest that the T104N mutation of CHMP2B inhibits morphological differentiation by triggering Golgi stress signaling, revealing a possible therapeutic molecular target for recovering potential molecular and cellular phenotypes underlying FTD/ALS7.}, } @article {pmid37606360, year = {2023}, author = {Bouché, TV and Coates, JR and Moore, SA and Faissler, D and Rishniw, M and Olby, NJ}, title = {Diagnosis and management of dogs with degenerative myelopathy: A survey of neurologists and rehabilitation professionals.}, journal = {Journal of veterinary internal medicine}, volume = {37}, number = {5}, pages = {1815-1820}, pmid = {37606360}, issn = {1939-1676}, mesh = {Humans ; Dogs ; Animals ; *Spinal Cord Diseases/diagnosis/therapy/veterinary ; *Amyotrophic Lateral Sclerosis/genetics/pathology/veterinary ; Neurologists ; Superoxide Dismutase-1/genetics ; Mutation ; *Dog Diseases/diagnosis/therapy/genetics ; }, abstract = {BACKGROUND: Antemortem diagnosis of degenerative myelopathy (DM) in dogs is presumptive and there are no accepted guidelines for the management of this condition.

HYPOTHESIS/OBJECTIVES: Describe current practices of neurology clinicians and physical rehabilitation professionals in the diagnosis and management of DM.

ANIMALS: None.

METHODS: Online surveys examining diagnosis and management of DM were constructed and distributed via neurology and rehabilitation listservs.

RESULTS: One hundred ninety neurology and 79 rehabilitation professionals from 20 countries participated. Most neurology (142/189) and rehabilitation (23/39) respondents required genetic testing for the superoxide dismutase 1 (SOD1) mutation and 82/189 neurologists also required spinal magnetic resonance imaging (MRI) for presumptive DM diagnosis. Most neurology respondents recommended exercise (187/190) and physical rehabilitation (184/190). Over 50% (102/190) of neurology respondents perform rechecks on dogs diagnosed with DM. Rehabilitation respondents reported preservation or improvement of strength (78/79) and coordination (77/79) as therapeutic goals. At-home exercises (75/79), underwater treadmill (64/79), gait training (55/79), and strength building exercises (65/79) were used to maintain strength (58/79), coordination (56/79), muscle mass (56/79), and improve overall wellbeing (54/79). Neurology respondents reported that owners elect euthanasia when dogs become nonambulatory paraparetic whereas rehabilitation respondents report euthanasia when paraplegia and incontinence develop.

The majority of dogs diagnosed with DM have not undergone advanced imaging, the combination of history, neurological findings, and genetic testing is heavily relied upon. Whereas the diagnosis of DM is frequently made by veterinary neurologists, continued care is often performed by rehabilitation professionals or primary veterinarians.}, } @article {pmid37605404, year = {2024}, author = {De, SK}, title = {New Pyrrolopyrimidines as LRRK2 Inhibitors for Treating Parkinson's Disease.}, journal = {Current medicinal chemistry}, volume = {31}, number = {33}, pages = {5477-5480}, pmid = {37605404}, issn = {1875-533X}, mesh = {Humans ; *Leucine-Rich Repeat Serine-Threonine Protein Kinase-2/antagonists & inhibitors/metabolism ; *Parkinson Disease/drug therapy/metabolism ; *Protein Kinase Inhibitors/chemistry/pharmacology/therapeutic use ; *Pyrimidines/chemistry/pharmacology/therapeutic use ; *Pyrroles/chemistry/pharmacology/therapeutic use ; Patents as Topic ; }, abstract = {This patent describes the novel pyrroloppyrimidine compounds as LRRK2 kinase inhibitors. The patent includes the synthesis of compounds, compositions containing them and their use in the treatment of or prevention of diseases associated with LRRK2 kinase activity, such as Parkinson's disease, Alzheimer's disease, and amyotrophic lateral sclerosis (ALS).}, } @article {pmid37605276, year = {2023}, author = {Estades Ayuso, V and Pickles, S and Todd, T and Yue, M and Jansen-West, K and Song, Y and González Bejarano, J and Rawlinson, B and DeTure, M and Graff-Radford, NR and Boeve, BF and Knopman, DS and Petersen, RC and Dickson, DW and Josephs, KA and Petrucelli, L and Prudencio, M}, title = {TDP-43-regulated cryptic RNAs accumulate in Alzheimer's disease brains.}, journal = {Molecular neurodegeneration}, volume = {18}, number = {1}, pages = {57}, pmid = {37605276}, issn = {1750-1326}, support = {RF1 NS120992/NS/NINDS NIH HHS/United States ; U19 AG063911/AG/NIA NIH HHS/United States ; P30 AG062677/AG/NIA NIH HHS/United States ; U54 NS123743/NS/NINDS NIH HHS/United States ; P01 NS084974/NS/NINDS NIH HHS/United States ; R01 AG037491/AG/NIA NIH HHS/United States ; R35 NS097273/NS/NINDS NIH HHS/United States ; }, mesh = {Humans ; *Alzheimer Disease/metabolism ; Amyotrophic Lateral Sclerosis ; Brain ; *DNA-Binding Proteins/metabolism ; Frontotemporal Dementia ; }, abstract = {BACKGROUND: Inclusions of TAR DNA-binding protein 43 kDa (TDP-43) has been designated limbic-predominant, age-related TDP-43 encephalopathy (LATE), with or without co-occurrence of Alzheimer's disease (AD). Approximately, 30-70% AD cases present TDP-43 proteinopathy (AD-TDP), and a greater disease severity compared to AD patients without TDP-43 pathology. However, it remains unclear to what extent TDP-43 dysfunction is involved in AD pathogenesis.

METHODS: To investigate whether TDP-43 dysfunction is a prominent feature in AD-TDP cases, we evaluated whether non-conserved cryptic exons, which serve as a marker of TDP-43 dysfunction in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD-TDP), accumulate in AD-TDP brains. We assessed a cohort of 192 post-mortem brains from three different brain regions: amygdala, hippocampus, and frontal cortex. Following RNA and protein extraction, qRT-PCR and immunoassays were performed to quantify the accumulation of cryptic RNA targets and phosphorylated TDP-43 pathology, respectively.

RESULTS: We detected the accumulation of misspliced cryptic or skiptic RNAs of STMN2, KCNQ2, UNC13A, CAMK2B, and SYT7 in the amygdala and hippocampus of AD-TDP cases. The topographic distribution of cryptic RNA accumulation mimicked that of phosphorylated TDP-43, regardless of TDP-43 subtype classification. Further, cryptic RNAs efficiently discriminated AD-TDP cases from controls.

CONCLUSIONS: Overall, our results indicate that cryptic RNAs may represent an intriguing new therapeutic and diagnostic target in AD, and that methods aimed at detecting and measuring these species in patient biofluids could be used as a reliable tool to assess TDP-43 pathology in AD. Our work also raises the possibility that TDP-43 dysfunction and related changes in cryptic splicing could represent a common molecular mechanism shared between AD-TDP and FTLD-TDP.}, } @article {pmid37604821, year = {2023}, author = {Gupta, AS and Patel, S and Premasiri, A and Vieira, F}, title = {At-home wearables and machine learning sensitively capture disease progression in amyotrophic lateral sclerosis.}, journal = {Nature communications}, volume = {14}, number = {1}, pages = {5080}, pmid = {37604821}, issn = {2041-1723}, support = {R01 NS117826/NS/NINDS NIH HHS/United States ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis ; Disease Progression ; Machine Learning ; Motor Neurons ; *Wearable Electronic Devices ; }, abstract = {Amyotrophic lateral sclerosis causes degeneration of motor neurons, resulting in progressive muscle weakness and impairment in motor function. Promising drug development efforts have accelerated in amyotrophic lateral sclerosis, but are constrained by a lack of objective, sensitive, and accessible outcome measures. Here we investigate the use of wearable sensors, worn on four limbs at home during natural behavior, to quantify motor function and disease progression in 376 individuals with amyotrophic lateral sclerosis. We use an analysis approach that automatically detects and characterizes submovements from passively collected accelerometer data and produces a machine-learned severity score for each limb that is independent of clinical ratings. We show that this approach produces scores that progress faster than the gold standard Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (-0.86 ± 0.70 SD/year versus -0.73 ± 0.74 SD/year), resulting in smaller clinical trial sample size estimates (N = 76 versus N = 121). This method offers an ecologically valid and scalable measure for potential use in amyotrophic lateral sclerosis trials and clinical care.}, } @article {pmid37604596, year = {2023}, author = {Bhaumik, S and Zwi, AB and Norton, R and Jagnoor, J}, title = {How and why snakebite became a global health priority: a policy analysis.}, journal = {BMJ global health}, volume = {8}, number = {8}, pages = {}, pmid = {37604596}, issn = {2059-7908}, mesh = {Humans ; Antivenins ; *Global Health ; *Health Priorities ; Policy Making ; *Snake Bites/epidemiology ; Animals ; }, abstract = {BACKGROUND: Snakebite was added to the WHO neglected tropical disease (NTD) list in 2017, followed by a World Health Assembly resolution in 2018, and an explicit global target being set to reduce the burden in 2019. We aimed to understand how and why snakebite became a global health priority.

METHODS: We conducted a policy case study, using in-depth interviews, and documents (peer-reviewed and grey literature) as data sources. We drew on Shiffman et al's framework on global health network to guide the analysis.

RESULTS: We conducted 20 interviews and examined 91 documents. The prioritisation of snakebite occurred in four phases: pre-crescendo, crescendo, de-crescendo and re-crescendo. The core snakebite network consisted of academics, which expanded during the re-crescendo phase to include civil society organisations and state actors. The involvement of diverse stakeholders led to better understanding of WHO processes. The use of intersecting and layered issue framing, framing solutions around snake antivenoms, in a background of cross-cultural fascination and fear of snakes enabled prioritisation in the re-crescendo phase. Ebbs and flows in legitimacy of the network and reluctant acceptance of snakebite within the NTD community are challenges.

CONCLUSION: Our analyses imply a fragile placement of snakebite in the global agenda. We identify two challenges, which needs to be overcome. The study highlights the need to review the WHO criteria for classifying diseases as NTD. We propose that future prioritisation analysis should consider identifying temporal patterns, as well as integrating legitimacy dimensions, as in our study.}, } @article {pmid37604125, year = {2023}, author = {Lee, SW and Lyu, YR and Yang, WK and Kim, SH and Kim, SY and Kang, W and Jung, IC and Lee, BJ and Choi, JY and Lee, MY and Park, YC}, title = {Efficacy and Safety of Yukmijihwang-Tang in the Treatment of Cough-Variant Asthma: Study Protocol for a Phase 2, Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial.}, journal = {Complementary medicine research}, volume = {30}, number = {5}, pages = {424-430}, doi = {10.1159/000533252}, pmid = {37604125}, issn = {2504-2106}, mesh = {Humans ; *Cough/drug therapy ; *Asthma/drug therapy ; Randomized Controlled Trials as Topic ; Multicenter Studies as Topic ; Clinical Trials, Phase II as Topic ; }, abstract = {BACKGROUND: Cough-variant asthma (CVA), a precursor of typical asthma, is the main cause of chronic cough. We hypothesize that yukmijihwang-tang (YJT), which has been used for chronic cough in traditional medicine and has been reported to have an anti-inflammatory effect, could be an adjuvant to asthma treatment.

METHODS: We plan a randomized, double-blind, placebo-controlled, multicenter, phase 2 trial to investigate the efficacy and safety of YJT in CVA patients. A total of 60 patients with CVA will be recruited and randomly assigned to either a high-dose YJT group, standard-dose YJT group, or control group (placebo) in a 1:1:1 allocation ratio after a 2-week run-in period. For the run-in period, only inhaled corticosteroids (ICSs) will be used, and the investigational drug will be administered once a day with concomitant ICS for 6 weeks. Data will be collected at baseline, week 3, and week 6, and the primary outcome measure will be the mean cough symptom score (CSS) change before and after medication. The secondary outcome measures will include the Leicester cough questionnaire-Korean version (LCQ-K) score, eosinophil count and eosinophil cationic protein level, pulmonary function test, and the number of uses of rescue medication, and so on.

CONCLUSION: This study aimed to evaluate the efficacy and safety of YJT in concomitant treatment with ICS in patients with CVA and to determine the optimal dosage of YJT. The results are expected to provide evidence for the use of YJT as an adjuvant treatment for CVA.

UNLABELLED: HintergrundCough-Variant-Asthma (CVA), eine Frühform von typischem Asthma, ist die Hauptursache von chronischem Husten. Unserer Vermutung nach könnte Yukmijihwang-Tang (YJT), das in der traditionellen Medizin zur Behandlung von chronischem Husten eingesetzt wird und das Berichten zufolge einen entzündungshemmenden Effekt hat, unterstützend in der Asthma-Therapie wirken.Methoden: Wir planen eine randomisierte, doppelblinde, placebokontrollierte, multizentrische Phase-2-Studie, um die Wirksamkeit und Sicherheit von YJT bei Patienten mit CVA zu untersuchen. Insgesamt werden 60 CVA-Patienten für die Studie rekrutiert und nach einer zweiwöchigen Run-in-Phase randomisiert im Verhältnis 1:1:1 einer Gruppe mit hochdosiertem YJT, einer Gruppe, die YJT in der Standarddosierung erhält oder einer Kontrollgruppe (Placebo) zugewiesen. Während der Run-in-Phase werden nur inhalative Corticosteroide (ICS) verwendet, und das Prüfpräparat wird über 6 Wochen einmal täglich gleichzeitig mit den ICS angewendet. Die Datenerhebung erfolgt bei Studienbeginn, in Woche 3 sowie in Woche 6, und das primäre Zielkriterium ist die Änderung des mittleren Hustenscores (cough symptom score, CSS) vor und nach der Anwendung der Medikamente. Zu den sekundären Zielkriterien gehören der Score des Leicester Hustenfragebogens - koreanische Version (LCQ-K), die Eosinophilenzahl und der Spiegel an eosinophilem kationischen Protein, Lungenfunktionstests sowie die Anzahl der Anwendungen von Bedarfsmedikation usw.SchlussfolgerungZiel dieser Studie ist es, die Wirksamkeit und Sicherheit von YJT bei gleichzeitiger Behandlung mit ICS bei Patienten mit CVA zu bewerten und die optimale YJT-Dosis zu ermitteln. Es wird erwartet, dass die Ergebnisse Belege für die Anwendung von YJT als adjuvante Therapie bei CVA liefern werden.Registrierung der StudieWHO International Clinical Trials Registry Platform, Clinical Research Information Service (CRIS), KCT0006994, registriert am 10. Februar 2022, https://cris.nih.go.kr/cris/search/detailSearch.do/21743.}, } @article {pmid37602847, year = {2023}, author = {Klingl, YE and Da Cruz, S and Van Den Bosch, L}, title = {Current Methods In ALS Research.}, journal = {Journal of visualized experiments : JoVE}, volume = {}, number = {193}, pages = {}, doi = {10.3791/65016}, pmid = {37602847}, issn = {1940-087X}, mesh = {Adult ; Humans ; Animals ; Mice ; *Amyotrophic Lateral Sclerosis ; Caenorhabditis elegans ; Zebrafish ; Motor Neurons ; Drosophila ; }, abstract = {Asakawa, K., Handa, H., Kawakami, K. Optogenetic phase transition of TDP-43 in spinal motor neurons of zebrafish larvae. Journal of Visualized Experiments. (180), e62932 (2022). Coyne, A. N., Rothstein, J. D. Nuclei isolation and super-resolution structured illumination microscopy for examining nucleoporin alterations in human neurodegeneration. (175), e62789 (2021). Currey, H. N., Liachko, N. F. Evaluation of motor impairment in C. elegans models of amyotrophic lateral sclerosis. (175), e62699 (2021). Hayes, L. R., Duan, L., Vidensky, S., Kalab, P. Nuclear transport assays in permeabilized mouse cortical neurons. (173), e62710 (2021). Krishnamurthy, K., Trotti, D., Pasinelli, P., Jensen, B. Real-time fluorescent measurements of synaptic functions in models of amyotrophic lateral sclerosis. (173), e62813 (2021). Loganathan, S., Ball H. E., Manzo, E., Zarnescu, D. C. Measuring glucose uptake in Drosophila models of TDP-43 proteinopathy. (174), e62936 (2021). Stilwell, G., Agudelo, A. Dissection and immunohistochemistry of the Drosophila adult leg to detect changes at the neuromuscular junction for an identified motor neuron. (180), e62844 (2022) Taga, A. et al. Establishment of an electrophysiological platform for modeling ALS with regionally-specific human pluripotent stem cell-derived astrocytes and neurons. (174), e62726 (2021). Stoklund Dittlau, K. et al., Generation of human motor units with functional neuromuscular junctions in microfluidic devices. (175), e62959 (2021).}, } @article {pmid37602649, year = {2023}, author = {Mehta, P and Raymond, J and Zhang, Y and Punjani, R and Han, M and Larson, T and Muravov, O and Lyles, RH and Horton, DK}, title = {Prevalence of amyotrophic lateral sclerosis in the United States, 2018.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {}, number = {}, pages = {1-7}, doi = {10.1080/21678421.2023.2245858}, pmid = {37602649}, issn = {2167-9223}, abstract = {OBJECTIVE: To estimate prevalent ALS cases in the United States for calendar year 2018.

METHODS: The National ALS Registry (Registry) compiled data from national administrative databases (from the Centers for Medicare and Medicaid Services, the Veterans Health Administration, and the Veterans Benefits Administration) and enrollment data voluntarily submitted through a web portal (www.cdc.gov/als). We used log-linear capture-recapture (CRC) model-based methodology to estimate the number of cases not ascertained by the Registry.

RESULTS: The Registry identified 21,655 cases of ALS in 2018, with an age-adjusted prevalence of 6.6 per 100,000 U.S. population. When CRC methods were used, an estimated 29,824 cases were identified, for an adjusted prevalence of 9.1 per 100,000 U.S. population. The demographics of cases of ALS did not change from previous year's reports. ALS continues to impact Whites, males, and persons over 50 years of age more so than other comparison groups. The results from the present report suggest case ascertainment for the Registry has improved, with the estimate of missing prevalent cases decreasing from 44% in 2017 to 27% in in 2018.

DISCUSSION: Consistent with previous estimates that used CRC, ALS prevalence in the United States is about 29,824 cases per year.}, } @article {pmid37602388, year = {2023}, author = {Sharma, S and Tomar, VR and Deep, S}, title = {Mechanism of the interaction of toxic SOD1 fibrils with two potent polyphenols: curcumin and quercetin.}, journal = {Physical chemistry chemical physics : PCCP}, volume = {25}, number = {34}, pages = {23081-23091}, doi = {10.1039/d3cp02120c}, pmid = {37602388}, issn = {1463-9084}, mesh = {Humans ; *Curcumin/pharmacology ; Quercetin/pharmacology ; Superoxide Dismutase-1 ; *Amyotrophic Lateral Sclerosis ; *Neurodegenerative Diseases ; Polyphenols ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a debilitating neurodegenerative disease commonly caused due to the aggregation of superoxide dismutase 1 (SOD1) protein. Finding inhibitors of SOD1 aggregation is of prime concern, but understanding the mechanistic action of inhibitors is equally important. Recent experiments found that two polyphenols, curcumin, and quercetin, have the ability to inhibit SOD1 aggregation. Quercetin was experimentally proven to break pre-formed fibrils into shorter segments, while curcumin did not significantly affect the pre-formed species. Here, we delve deeper into understanding the mechanism of action of quercetin and curcumin on pre-formed octameric fibrils of SOD1 ([28]PVKVWGSIKGL[38]: chains A-H) with the help of molecular dynamics (MD) simulations of a fibril docked polyphenol complex. Our results suggest that quercetin shows π-π stacking interaction with one of the key residues for toxic amyloid formation, Trp 32 of chains D, E, and F, and breaks the peptide chains G, and H from the rest of the fibril. On the other hand, curcumin binds to the hydrophobic amino acids of almost all the chains B-H and stabilizes the fibril rather than destabilizing it. Binding free energy calculations using MM/PBSA showed that curcumin binds more strongly to the SOD1 fibril due to greater van der Waals interactions compared to quercetin. These findings provide insights for the development of potential ALS treatments.}, } @article {pmid37602264, year = {2023}, author = {Nakamori, M and Ishikawa, R and Watanabe, T and Toko, M and Naito, H and Takahashi, T and Simizu, Y and Yamazaki, Y and Maruyama, H}, title = {Swallowing sound evaluation using an electronic stethoscope and artificial intelligence analysis for patients with amyotrophic lateral sclerosis.}, journal = {Frontiers in neurology}, volume = {14}, number = {}, pages = {1212024}, pmid = {37602264}, issn = {1664-2295}, abstract = {BACKGROUND AND PURPOSE: Non-invasive, simple, and repetitive swallowing evaluation is required to prevent aspiration pneumonia in neurological care. We investigated the usefulness of swallowing sound evaluation in patients with amyotrophic lateral sclerosis (ALS) using our new electronic stethoscope artificial intelligence (AI) analysis tool.

METHODS: We studied patients with ALS who provided written informed consent. We used an electronic stethoscope, placed a Bluetooth-enabled electronic stethoscope on the upper end of the sternum, performed a 3-mL water swallow three times, and remotely identified the intermittent sound components of the water flow caused at that time by AI, with the maximum value as the swallowing sound index. We examined the correlation between the swallowing sound index and patient background, including swallowing-related parameters.

RESULTS: We evaluated 24 patients with ALS (age 64.0 ± 11.8 years, 13 women, median duration of illness 17.5 months). The median ALS Functional Rating Scale-Revised (ALSFRS-R) score was 41 (minimum 18, maximum 47). In all cases, the mean swallowing sound index was 0.209 ± 0.088. A multivariate analysis showed that a decrease in the swallowing sound index was significantly associated with a low ALSFRS-R score, an ALSFRS-R bulbar symptom score, % vital capacity, tongue pressure, a Mann Assessment of Swallowing Ability (MASA) score, and a MASA pharyngeal phase-related score.

CONCLUSION: Swallowing sound evaluation using an electronic stethoscope AI analysis showed a correlation with existing indicators in swallowing evaluation in ALS and suggested its usefulness as a new method. This is expected to be a useful examination method in home and remote medical care.}, } @article {pmid37602234, year = {2023}, author = {Luzzi, A and Wang, F and Li, S and Iacovino, M and Chou, TF}, title = {Skeletal muscle cell protein dysregulation highlights the pathogenesis mechanism of myopathy-associated p97/VCP R155H mutations.}, journal = {Frontiers in neurology}, volume = {14}, number = {}, pages = {1211635}, pmid = {37602234}, issn = {1664-2295}, support = {R01 NS102279/NS/NINDS NIH HHS/United States ; }, abstract = {p97/VCP, a hexametric member of the AAA-ATPase superfamily, has been associated with a wide range of cellular protein pathways, such as proteasomal degradation, the unfolding of polyubiquitinated proteins, and autophagosome maturation. Autosomal dominant p97/VCP mutations cause a rare hereditary multisystem disorder called IBMPFD/ALS (Inclusion Body Myopathy with Paget's Disease and Frontotemporal Dementia/Amyotrophic Lateral Sclerosis), characterized by progressive weakness and subsequent atrophy of skeletal muscles, and impacting bones and brains, such as Parkinson's disease, Lewy body disease, Huntington's disease, and amyotrophic lateral ALS. Among all disease-causing mutations, Arginine 155 to Histidine (R155H/+) was reported to be the most common one, affecting over 50% of IBMPFD patients, resulting in disabling muscle weakness, which might eventually be life-threatening due to cardiac and respiratory muscle involvement. Induced pluripotent stem cells (iPSCs) offer an unlimited resource of cells to study pathology's underlying molecular mechanism, perform drug screening, and investigate regeneration. Using R155H/+ patients' fibroblasts, we generated IPS cells and corrected the mutation (Histidine to Arginine, H155R) to generate isogenic control cells before differentiating them into myotubes. The further proteomic analysis allowed us to identify differentially expressed proteins associated with the R155H mutation. Our results showed that R155H/+ cells were associated with dysregulated expression of several proteins involved in skeletal muscle function, cytoskeleton organization, cell signaling, intracellular organelles organization and function, cell junction, and cell adhesion. Our findings provide molecular evidence of dysfunctional protein expression in R155H/+ myotubes and offer new therapeutic targets for treating IBMPFD/ALS.}, } @article {pmid37601533, year = {2023}, author = {Guareschi, S and Ravasi, M and Baldessari, D and Pozzi, S and Zaffino, T and Melazzini, M and Ambrosini, A}, title = {The positive impact on translational research of Fondazione italiana di ricerca per la Sclerosi Laterale Amiotrofica (AriSLA), a non-profit foundation focused on amyotrophic lateral sclerosis. Convergence of ex-ante evaluation and ex-post outcomes when goals are set upfront.}, journal = {Frontiers in research metrics and analytics}, volume = {8}, number = {}, pages = {1067981}, pmid = {37601533}, issn = {2504-0537}, abstract = {Charities investing on rare disease research greatly contribute to generate ground-breaking knowledge with the clear goal of finding a cure for their condition of interest. Although the amount of their investments may be relatively small compared to major funders, the advocacy groups' clear mission promotes innovative research and aggregates highly motivated and mission-oriented scientists. Here, we illustrate the case of Fondazione italiana di ricerca per la Sclerosi Laterale Amiotrofica (AriSLA), the main Italian funding agency entirely dedicated to amyotrophic lateral sclerosis research. An international benchmark analysis of publications derived from AriSLA-funded projects indicated that their mean relative citation ratio values (iCite dashboard, National Institutes of Health, U.S.) were very high, suggesting a strong influence on the referring international scientific community. An interesting trend of research toward translation based on the "triangle of biomedicine" and paper citations (iCite) was also observed. Qualitative analysis on researchers' accomplishments was convergent with the bibliometric data, indicating a high level of performance of several working groups, lines of research that speak of progression toward clinical translation, and one study that has progressed from the investigation of cellular mechanisms to a Phase 2 international clinical trial. The key elements of the success of the AriSLA investment lie in: (i) the clear definition of the objectives (research with potential impact on patients, no matter how far), (ii) a rigorous peer-review process entrusted to an international panel of experts, (iii) diversification of the portfolio with ad hoc selection criteria, which also contributed to bringing new experts and younger scientists to the field, and (iv) a close interaction of AriSLA stakeholders with scientists, who developed a strong sense of belonging. Periodic review of the portfolio of investments is a vital practice for funding agencies. Sharing information between funding agencies about their own policies and research assessment methods and outcomes help guide the international debate on funding strategies and research directions to be undertaken, particularly in the field of rare diseases, where synergy is a relevant enabling factor.}, } @article {pmid37600819, year = {2023}, author = {Räuber, S and Nelke, C and Schroeter, CB and Barman, S and Pawlitzki, M and Ingwersen, J and Akgün, K and Günther, R and Garza, AP and Marggraf, M and Dunay, IR and Schreiber, S and Vielhaber, S and Ziemssen, T and Melzer, N and Ruck, T and Meuth, SG and Herty, M}, title = {Classifying flow cytometry data using Bayesian analysis helps to distinguish ALS patients from healthy controls.}, journal = {Frontiers in immunology}, volume = {14}, number = {}, pages = {1198860}, pmid = {37600819}, issn = {1664-3224}, mesh = {*Flow Cytometry/classification/methods ; Bayes Theorem ; Algorithms ; *Amyotrophic Lateral Sclerosis/diagnosis ; Humans ; Models, Theoretical ; Male ; Female ; Adult ; Middle Aged ; Aged ; Aged, 80 and over ; }, abstract = {INTRODUCTION: Given its wide availability and cost-effectiveness, multidimensional flow cytometry (mFC) became a core method in the field of immunology allowing for the analysis of a broad range of individual cells providing insights into cell subset composition, cellular behavior, and cell-to-cell interactions. Formerly, the analysis of mFC data solely relied on manual gating strategies. With the advent of novel computational approaches, (semi-)automated gating strategies and analysis tools complemented manual approaches.

METHODS: Using Bayesian network analysis, we developed a mathematical model for the dependencies of different obtained mFC markers. The algorithm creates a Bayesian network that is a HC tree when including raw, ungated mFC data of a randomly selected healthy control cohort (HC). The HC tree is used to classify whether the observed marker distribution (either patients with amyotrophic lateral sclerosis (ALS) or HC) is predicted. The relative number of cells where the probability q is equal to zero is calculated reflecting the similarity in the marker distribution between a randomly chosen mFC file (ALS or HC) and the HC tree.

RESULTS: Including peripheral blood mFC data from 68 ALS and 35 HC, the algorithm could correctly identify 64/68 ALS cases. Tuning of parameters revealed that the combination of 7 markers, 200 bins, and 20 patients achieved the highest AUC on a significance level of p < 0.0001. The markers CD4 and CD38 showed the highest zero probability. We successfully validated our approach by including a second, independent ALS and HC cohort (55 ALS and 30 HC). In this case, all ALS were correctly identified and side scatter and CD20 yielded the highest zero probability. Finally, both datasets were analyzed by the commercially available algorithm 'Citrus', which indicated superior ability of Bayesian network analysis when including raw, ungated mFC data.

DISCUSSION: Bayesian network analysis might present a novel approach for classifying mFC data, which does not rely on reduction techniques, thus, allowing to retain information on the entire dataset. Future studies will have to assess the performance when discriminating clinically relevant differential diagnoses to evaluate the complementary diagnostic benefit of Bayesian network analysis to the clinical routine workup.}, } @article {pmid37600635, year = {2023}, author = {Fathi, M and Sedaghat, M and Ahadi, H}, title = {Quality of Life of Amyotrophic Lateral Sclerosis Patients in Iran.}, journal = {Medical journal of the Islamic Republic of Iran}, volume = {37}, number = {}, pages = {76}, pmid = {37600635}, issn = {1016-1430}, abstract = {BACKGROUND: Amyotrophic Lateral Sclerosis (ALS) is a rare disease that can bring different emotional, physical, and psychological burdens. This study aimed to investigate the quality of life in patients with ALS.

METHODS: This is a cross-sectional study. Fifty-two patients contributed in this study. The setting was an ALS clinic in Iran. A mixed method was used in this study. We applied a short form of the WHO Quality of Life questionnaire (WHOQOL) to measure the quality of life of patients. Also, all participants were interviewed through the semi-structured interview guide. To measure physical strength and functioning the Appel ALS Rating Scale (AALS) was employed in this study. To analyze the data, a two-tailed t-test and x2 test were used.

RESULTS: 42.3% of the participants were female. The age of the participants ranged between 28 to 81 (mean=57.6). The disease duration ranged from 0.07 to 14 years (mean=1.8). The overall mean QOL was 58.7 (±8.1). The overall mean of the AALS score was 74.4 (±24.2). The results of the qualitative part of the study showed four psychosocial themes: (1) internal personality traits, communicating with friends and family; (2) religion and spirituality; (3) stress, mood changes, and difficult relationship; and (4) changes in lifestyle, work, leisure time and financial situation.

CONCLUSION: Despite recent advances, ALS is still one of the diseases for which there is no effective treatment. Paying attention to psychosocial issues in patients with ALS can play a very important role in increasing the quality of life of patients.}, } @article {pmid37599994, year = {2023}, author = {Baker, BH and Zhang, S and Simon, JM and McLarnan, SM and Chung, WK and Pearson, BL}, title = {Environmental carcinogens disproportionally mutate genes implicated in neurodevelopmental disorders.}, journal = {Frontiers in neuroscience}, volume = {17}, number = {}, pages = {1106573}, pmid = {37599994}, issn = {1662-4548}, support = {P50 HD103573/HD/NICHD NIH HHS/United States ; }, abstract = {INTRODUCTION: De novo mutations contribute to a large proportion of sporadic psychiatric and developmental disorders, yet the potential role of environmental carcinogens as drivers of causal de novo mutations in neurodevelopmental disorders is poorly studied.

METHODS: To explore environmental mutation vulnerability of disease-associated gene sets, we analyzed publicly available whole genome sequencing datasets of mutations in human induced pluripotent stem cell clonal lines exposed to 12 classes of environmental carcinogens, and human lung cancers from individuals living in highly polluted regions. We compared observed rates of exposure-induced mutations in disease-related gene sets with the expected rates of mutations based on control genes randomly sampled from the genome using exact binomial tests. To explore the role of sequence characteristics in mutation vulnerability, we modeled the effects of sequence length, gene expression, and percent GC content on mutation rates of entire genes and gene coding sequences using multivariate Quasi-Poisson regressions.

RESULTS: We demonstrate that several mutagens, including radiation and polycyclic aromatic hydrocarbons, disproportionately mutate genes related to neurodevelopmental disorders including autism spectrum disorders, schizophrenia, and attention deficit hyperactivity disorder. Other disease genes including amyotrophic lateral sclerosis, Alzheimer's disease, congenital heart disease, orofacial clefts, and coronary artery disease were generally not mutated more than expected. Longer sequence length was more strongly associated with elevated mutations in entire genes compared with mutations in coding sequences. Increased expression was associated with decreased coding sequence mutation rate, but not with the mutability of entire genes. Increased GC content was associated with increased coding sequence mutation rates but decreased mutation rates in entire genes.

DISCUSSION: Our findings support the possibility that neurodevelopmental disorder genetic etiology is partially driven by a contribution of environment-induced germ line and somatic mutations.}, } @article {pmid37599467, year = {2024}, author = {Sung, H and Lloyd, TE}, title = {Disrupted endoplasmic reticulum-mediated autophagosomal biogenesis in a Drosophila model of C9-ALS-FTD.}, journal = {Autophagy}, volume = {20}, number = {1}, pages = {94-113}, pmid = {37599467}, issn = {1554-8635}, support = {P30 NS050274/NS/NINDS NIH HHS/United States ; R01 NS094239/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; *Frontotemporal Dementia/genetics/metabolism ; *Amyotrophic Lateral Sclerosis/genetics/metabolism ; Drosophila ; DNA Repeat Expansion ; Autophagy/genetics ; Transcription Factors ; }, abstract = {3R: UAS construct expressing 3 G4C2 repeats (used as control); 3WJ: three-way junction; 12R: UAS construct expressing leader sequence and 12 G4C2 repeats; 30R: UAS construct expressing 30 G4C2 repeats; 36R: UAS construct expressing 36 G4C2 repeats; 44R: UAS construct expressing leader sequence and 44 G4C2 repeats; ALS: amyotrophic lateral sclerosis; Atg: autophagy related; atl: atlastin; C9-ALS-FTD: ALS or FTD caused by hexanuleotide repeat expansion in C9orf72; ER: endoplasmic reticulum; FTD: frontotemporal dementia; HRE: GGGGCC hexanucleotide repeat expansion; HSP: hereditary spastic paraplegia; Lamp1: lysosomal associated membrane protein 1; MT: microtubule; NMJ: neuromuscular junction; Rab: Ras-associated binding GTPase; RAN: repeat associated non-AUG (RAN) translation; RO-36: UAS construct expression "RNA-only" version of 36 G4C2 repeats in which stop codons in all six reading frames are inserted.; Rtnl1: Reticulon-like 1; SN: segmental nerve; TFEB/Mitf: transcription factor EB/microphthalmia associated transcription factor (Drosophila ortholog of TFEB); TrpA1: transient receptor potential cation channel A1; VAPB: VAMP associated protein B and C; VNC: ventral nerve cord (spinal cord in Drosophila larvae).}, } @article {pmid37598759, year = {2023}, author = {Rani, N and Alam, MM and Jamal, A and Bin Ghaffar, U and Parvez, S}, title = {Caenorhabditis elegans: A transgenic model for studying age-associated neurodegenerative diseases.}, journal = {Ageing research reviews}, volume = {91}, number = {}, pages = {102036}, doi = {10.1016/j.arr.2023.102036}, pmid = {37598759}, issn = {1872-9649}, mesh = {Animals ; Humans ; *Neurodegenerative Diseases/genetics ; Caenorhabditis elegans/metabolism ; *Alzheimer Disease/genetics ; *Parkinson Disease ; *Huntington Disease/genetics ; }, abstract = {Neurodegenerative diseases (NDs) are a heterogeneous group of aging-associated ailments characterized by interrupting cellular proteostasic machinery and the misfolding of distinct proteins to form toxic aggregates in neurons. Neurodegenerative diseases, which include Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), and others, are becoming an increasing threat to human health worldwide. The degeneration and death of certain specific groups of neurons are the hallmarks of these diseases. Over the past decades, Caenorhabditis eleganshas beenwidely used as a transgenic model to investigate biological processes related to health and disease. The nematode Caenorhabditis elegans (C. elegans) has developed as a powerful tool for studying disease mechanisms due to its ease of genetic handling and instant cultivation while providing a whole-animal system amendable to several molecular and biochemical techniques. In this review, we elucidate the potential of C. elegans as a versatile platform for systematic dissection of the molecular basis of human disease, focusing on neurodegenerative disorders, and may help better our understanding of the disease mechanisms and search for new therapeutics for these devastating diseases.}, } @article {pmid37597354, year = {2023}, author = {Alaoui Mansouri, M and Kharbach, M and El Maouardi, M and Barra, I and Bouklouze, A}, title = {Quantification of ciprofloxacin in pharmaceutical products from various brands using FT-NIR: A comparative investigation of PLS and MCR-ALS.}, journal = {Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy}, volume = {303}, number = {}, pages = {123268}, doi = {10.1016/j.saa.2023.123268}, pmid = {37597354}, issn = {1873-3557}, mesh = {*Excipients ; Least-Squares Analysis ; *Chemometrics ; Ciprofloxacin ; Spectroscopy, Fourier Transform Infrared ; }, abstract = {This study aims to quantify ciprofloxacin in commercial tablets with varying excipient compositions using Fourier Transform Near-Infrared Spectroscopy (FT-NIR) and chemometric models: Partial Least Squares (PLS) and Multivariate Curve Resolution - Alternating Least Squares (MCR-ALS). Matrix variation, arising from differences in excipient compositions among the tablets, can impact quantification accuracy. We discuss this phenomenon, emphasizing potential issues introduced by varying certain excipients and its importance in reliable ciprofloxacin quantification. We evaluated the performance of PLS and MCR-ALS models independently on two sets of tablets, each containing the same drug substance but different excipients. The statistical results revealed promising results with PLS prediction error of 0.38% w/w of the first set and 0.47% w/w of the second set, while MCR-ALS achieved prediction errors of 0.67% w/w of the first set and 1.76% w/w of the second set. To address the challenge of matrix variation, we developed single models for PLS and MCR-ALS using a dataset combining both first and second sets. The PLS single model demonstrated a prediction error of 4.3% w/w and a relative error of 6.41% w/w, while the MCR-ALS single model showed a prediction error of 1.88% w/w and a relative error of 1.29% w/w. We then assessed the performance of the single PLS and MCR-ALS models developed based on the combination of the first and the second set in quantifying ciprofloxacin in various commercial tablet brands containing new excipients. The PLS model achieved a prediction error ranging between 6.2% w/w and 8.39% w/w, with relative errors varied between 8.53% w/w and 12.82% w/w. On the other hand, the MCR-ALS model had a prediction error between 1.11% w/w and 2.66% w/w, and the relative errors ranging from 0.8% to 1.74% w/w.}, } @article {pmid37596282, year = {2023}, author = {Liu, S and Heumüller, SE and Hossinger, A and Müller, SA and Buravlova, O and Lichtenthaler, SF and Denner, P and Vorberg, IM}, title = {Reactivated endogenous retroviruses promote protein aggregate spreading.}, journal = {Nature communications}, volume = {14}, number = {1}, pages = {5034}, pmid = {37596282}, issn = {2041-1723}, mesh = {Humans ; *Endogenous Retroviruses/genetics ; Protein Aggregates ; *Amyotrophic Lateral Sclerosis ; Antiviral Agents ; *Prions ; }, abstract = {Prion-like spreading of protein misfolding is a characteristic of neurodegenerative diseases, but the exact mechanisms of intercellular protein aggregate dissemination remain unresolved. Evidence accumulates that endogenous retroviruses, remnants of viral germline infections that are normally epigenetically silenced, become upregulated in neurodegenerative diseases such as amyotrophic lateral sclerosis and tauopathies. Here we uncover that activation of endogenous retroviruses affects prion-like spreading of proteopathic seeds. We show that upregulation of endogenous retroviruses drastically increases the dissemination of protein aggregates between cells in culture, a process that can be inhibited by targeting the viral envelope protein or viral protein processing. Human endogenous retrovirus envelopes of four different clades also elevate intercellular spreading of proteopathic seeds, including pathological Tau. Our data support a role of endogenous retroviruses in protein misfolding diseases and suggest that antiviral drugs could represent promising candidates for inhibiting protein aggregate spreading.}, } @article {pmid37595581, year = {2023}, author = {Yang, M and Liu, M and Sánchez, YF and Avazzadeh, S and Quinlan, LR and Liu, G and Lu, Y and Yang, G and O'Brien, T and Henshall, DC and Hardiman, O and Shen, S}, title = {A novel protocol to derive cervical motor neurons from induced pluripotent stem cells for amyotrophic lateral sclerosis.}, journal = {Stem cell reports}, volume = {18}, number = {9}, pages = {1870-1883}, pmid = {37595581}, issn = {2213-6711}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis ; *Induced Pluripotent Stem Cells ; Motor Neurons ; Autophagy ; Cell Differentiation ; *Osteochondrodysplasias ; }, abstract = {Sporadic amyotrophic lateral sclerosis (sALS) is the majority of ALS, and the lack of appropriate disease models has hindered its research. Induced pluripotent stem cell (iPSC) technology now permits derivation of iPSCs from somatic cells of sALS patients to investigate disease phenotypes and mechanisms. Most existing differentiation protocols are time-consuming or low efficient in generating motor neurons (MNs). Here we report a rapid and simple protocol to differentiate MNs in monolayer culture using small molecules, which led to nearly pure neural stem cells in 6 days, robust OLIG2[+] pMNs (73%-91%) in 12 days, enriched CHAT[+] cervical spinal MNs (sMNs) (88%-97%) in 18 days, and functionally mature sMNs in 28 days. This simple and reproducible protocol permitted the identification of hyperexcitability phenotypes in our sALS iPSC-derived sMNs, and its application in neurodegenerative diseases should facilitate in vitro disease modeling, drug screening, and the development of cell therapy.}, } @article {pmid37593923, year = {2023}, author = {Pino, MG and Rich, KA and Hall, NJ and Jones, ML and Fox, A and Musier-Forsyth, K and Kolb, SJ}, title = {Heterogeneous splicing patterns resulting from KIF5A variants associated with amyotrophic lateral sclerosis.}, journal = {Human molecular genetics}, volume = {32}, number = {22}, pages = {3166-3180}, doi = {10.1093/hmg/ddad134}, pmid = {37593923}, issn = {1460-2083}, mesh = {Humans ; Mice ; Animals ; *Amyotrophic Lateral Sclerosis/genetics ; *Neurodegenerative Diseases/genetics ; RNA Splicing/genetics ; RNA, Messenger/genetics ; Exons/genetics ; Kinesins/genetics/metabolism ; }, abstract = {Single-nucleotide variants (SNVs) in the gene encoding Kinesin Family Member 5A (KIF5A), a neuronal motor protein involved in anterograde transport along microtubules, have been associated with amyotrophic lateral sclerosis (ALS). ALS is a rapidly progressive and fatal neurodegenerative disease that primarily affects the motor neurons. Numerous ALS-associated KIF5A SNVs are clustered near the splice-site junctions of the penultimate exon 27 and are predicted to alter the carboxy-terminal (C-term) cargo-binding domain of KIF5A. Mis-splicing of exon 27, resulting in exon exclusion, is proposed to be the mechanism by which these SNVs cause ALS. Whether all SNVs proximal to exon 27 result in exon exclusion is unclear. To address this question, we designed an in vitro minigene splicing assay in human embryonic kidney 293 cells, which revealed heterogeneous site-specific effects on splicing: only 5' splice-site (5'ss) SNVs resulted in exon skipping. We also quantified splicing in select clustered, regularly interspaced, short palindromic repeats-edited human stem cells, differentiated to motor neurons, and in neuronal tissues from a 5'ss SNV knock-in mouse, which showed the same result. Moreover, the survival of representative 3' splice site, 5'ss, and truncated C-term variant KIF5A (v-KIF5A) motor neurons was severely reduced compared with wild-type motor neurons, and overt morphological changes were apparent. While the total KIF5A mRNA levels were comparable across the cell lines, the total KIF5A protein levels were decreased for v-KIF5A lines, suggesting an impairment of protein synthesis or stability. Thus, despite the heterogeneous effect on ribonucleic acid splicing, KIF5A SNVs similarly reduce the availability of the KIF5A protein, leading to axonal transport defects and motor neuron pathology.}, } @article {pmid37592793, year = {2024}, author = {Manera, U and Matteoni, E and Canosa, A and Callegaro, S and Casale, F and Marchis, D and Vasta, R and Moglia, C and Chiò, A and Calvo, A}, title = {Mycotoxins and Amyotrophic Lateral Sclerosis: Food Exposure, Nutritional Implications and Dietary Solutions.}, journal = {CNS & neurological disorders drug targets}, volume = {23}, number = {5}, pages = {562-572}, pmid = {37592793}, issn = {1996-3181}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/epidemiology ; *Mycotoxins/toxicity ; Animals ; Environmental Exposure/adverse effects ; Food Contamination ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder determined by a combination of both genetic and environmental factors. Despite wide investigations, the role of chronic exposure to environmental pollutants is still rather unknown. Among natural toxins, the mycotoxins have received major attention only in the last few years, due to both technical and scientific achievements that allowed to disentangle many important features of the complex fungal biology. Whereas the effects of acute and high-dose mycotoxin exposure are well known, the potential effects of chronic and low-dose exposure on neurodegeneration have not been broadly elucidated. In this review, we have summarized all the studies concerning environmental exposure to unknown substances that caused ALS outbreaks all over the world, reinterpreting in light of the new scientific acquisitions and highlighting the potential and neglected role of mycotoxins. Then, we focused on recent papers about food exposure to mycotoxin, mycobiome and fungal infections in ALS and other neurodegenerative diseases. We analyzed the gaps of current literature that lead to an undervaluation of mycotoxins as detrimental molecules. By listing all the most important mycotoxins and analyzing all the biological pathways that they can affect, we explained the reasons why they need to be considered in the next epidemiological studies on ALS and other neurodegenerative and neuroinflammatory diseases. In conclusion, after suggesting some possible solutions to mitigate mycotoxin exposure risk, we affirm that future collaborations between scientists and policymakers are important to develop sustainable interventions and promote health through dietary diversity.}, } @article {pmid37591957, year = {2023}, author = {Mandrioli, J and D'Amico, R and Zucchi, E and De Biasi, S and Banchelli, F and Martinelli, I and Simonini, C and Lo Tartaro, D and Vicini, R and Fini, N and Gianferrari, G and Pinti, M and Lunetta, C and Gerardi, F and Tarlarini, C and Mazzini, L and De Marchi, F and Scognamiglio, A and Sorarù, G and Fortuna, A and Lauria, G and Bella, ED and Caponnetto, C and Meo, G and Chio, A and Calvo, A and Cossarizza, A}, title = {Randomized, double-blind, placebo-controlled trial of rapamycin in amyotrophic lateral sclerosis.}, journal = {Nature communications}, volume = {14}, number = {1}, pages = {4970}, pmid = {37591957}, issn = {2041-1723}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy/genetics ; Interleukin-18 ; Quality of Life ; Ribosomal Proteins ; Autophagy ; }, abstract = {In preclinical studies rapamycin was found to target neuroinflammation, by expanding regulatory T cells, and affecting autophagy, two pillars of amyotrophic lateral sclerosis (ALS) pathogenesis. Herein we report a multicenter, randomized, double-blind trial, in 63 ALS patients who were randomly assigned in a 1:1:1 ratio to receive rapamycin 2 mg/m[2]/day,1 mg/m[2]/day or placebo (EUDRACT 2016-002399-28; NCT03359538). The primary outcome, the number of patients exhibiting an increase >30% in regulatory T cells from baseline to treatment end, was not attained. Secondary outcomes were changes from baseline of T, B, NK cell subpopulations, inflammasome mRNA expression and activation status, S6-ribosomal protein phosphorylation, neurofilaments; clinical outcome measures of disease progression; survival; safety and quality of life. Of the secondary outcomes, rapamycin decreased mRNA relative expression of the pro-inflammatory cytokine IL-18, reduced plasmatic IL-18 protein, and increased the percentage of classical monocytes and memory switched B cells, although no corrections were applied for multiple tests. In conclusion, we show that rapamycin treatment is well tolerated and provides reassuring safety findings in ALS patients, but further trials are necessary to understand the biological and clinical effects of this drug in ALS.}, } @article {pmid37591233, year = {2023}, author = {Donohue, C and Robison, R and Steele, CM and Wymer, JP and Plowman, EK}, title = {Profiling Number of Swallows per Bolus and Residue in Individuals With Amyotrophic Lateral Sclerosis.}, journal = {Journal of speech, language, and hearing research : JSLHR}, volume = {66}, number = {10}, pages = {3763-3772}, pmid = {37591233}, issn = {1558-9102}, support = {K00 AG076123/AG/NIA NIH HHS/United States ; R01 AG077481/AG/NIA NIH HHS/United States ; R01 DC011020/DC/NIDCD NIH HHS/United States ; R01 NS100859/NS/NINDS NIH HHS/United States ; }, mesh = {Humans ; *Deglutition Disorders/etiology ; *Amyotrophic Lateral Sclerosis/complications ; Deglutition ; Fluoroscopy/methods ; Food ; Pharynx ; }, abstract = {PURPOSE: Swallowing efficiency impairments are the most prevalent and earliest manifestation of dysphagia in people with amyotrophic lateral sclerosis (pALS). We aimed to profile number of swallows elicited in pALS across thin liquid, moderately thick liquid, extremely thick liquid, and crackers compared to expected healthy reference data and to determine relationships between degree of pharyngeal residue, number of elicited swallows, and swallowing safety.

METHOD: pALS underwent standardized videofluoroscopic swallowing studies of 10 bolus trials. Trained raters performed duplicate, independent, and blinded ratings to derive Dynamic Imaging Grade of Swallowing Toxicity (DIGEST) efficiency and safety grades and Analysis of Swallowing Physiology: Events, Kinematics, and Timing (ASPEKT) percent total pharyngeal residue. Number of swallows per bolus was quantified (1 = typical, 2 = atypically high, 3 = extremely high). Kruskal-Wallis, Pearson chi-square, and odds ratio analyses were performed at bolus and participant levels.

KEY RESULTS: At the bolus level (N = 2,523), number of swallows per bolus was observed to be, in rank order, as follows: atypically high (49.1%), extremely high (28.5%), and typical (22.4%). Mean number of swallows significantly differed by International Dysphagia Diet Standardisation Initiative level (p < .0001), with a higher number of swallows elicited in pALS for moderately thick versus thin liquids, extremely thick liquids, and crackers, p < .0001. Number of swallows per bolus increased with increasing DIGEST efficiency grades (p < .0001). Positive correlations were observed between ASPEKT percent residue and number of swallows for thin (r = .24) and moderately thick (r = .16) liquids, p < .05. DIGEST efficiency and safety grades were not significantly associated (p > .05).

CONCLUSION AND INFERENCES: pALS demonstrated a higher number of swallows per bolus compared to healthy reference data that may represent a compensation for reductions in swallowing efficiency to clear pharyngeal residue.}, } @article {pmid37590965, year = {2023}, author = {Rani, A and Saini, V and Patra, P and Prashar, T and Pandey, RK and Mishra, A and Jha, HC}, title = {Epigallocatechin Gallate: A Multifaceted Molecule for Neurological Disorders and Neurotropic Viral Infections.}, journal = {ACS chemical neuroscience}, volume = {14}, number = {17}, pages = {2968-2980}, doi = {10.1021/acschemneuro.3c00368}, pmid = {37590965}, issn = {1948-7193}, mesh = {Humans ; *Alzheimer Disease ; *Epstein-Barr Virus Infections ; Glycogen Synthase Kinase 3 ; Phosphatidylinositol 3-Kinases ; *Zika Virus Infection ; Herpesvirus 4, Human ; *Zika Virus ; *Nervous System Diseases ; }, abstract = {Epigallocatechin-3-gallate (EGCG), a polyphenolic moiety found in green tea extracts, exhibits pleiotropic bioactivities to combat many diseases including neurological ailments. These neurological diseases include Alzheimer's disease, multiple sclerosis, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. For instance, in the case of Alzheimer's disease, the formation of a β-sheet in the region of the 10th-21st amino acids was significantly reduced in EGCG-induced oligomeric samples of Aβ40. Its interference induces the formation of Aβ structures with an increase in intercenter-of-mass distances, reduction in interchain/intrachain contacts, reduction in β-sheet propensity, and increase in α-helix. Besides, numerous neurotropic viruses are known to instigate or aggravate neurological ailments. It exerts an effect on the oxidative damage caused in neurodegenerative disorders by acting on GSK3-β, PI3K/Akt, and downstream signaling pathways via caspase-3 and cytochrome-c. EGCG also diminishes these viral-mediated effects, such as EGCG delayed HSV-1 infection by blocking the entry for virions, inhibitory effects on NS3/4A protease or NS5B polymerase of HCV and potent inhibitor of ZIKV NS2B-NS3pro/NS3 serine protease (NS3-SP). It showed a reduction in the neurotoxic properties of HIV-gp120 and Tat in the presence of IFN-γ. EGCG also involves numerous viral-mediated inflammatory cascades, such as JAK/STAT. Nonetheless, it also inhibits the Epstein-Barr virus replication protein (Zta and Rta). Moreover, it also impedes certain viruses (influenza A and B strains) by hijacking the endosomal and lysosomal compartments. Therefore, the current article aims to describe the importance of EGCG in numerous neurological diseases and its inhibitory effect against neurotropic viruses.}, } @article {pmid37590829, year = {2023}, author = {Lee-Iannotti, JK}, title = {Sleep Disorders in Patients with Neurologic Disease.}, journal = {Continuum (Minneapolis, Minn.)}, volume = {29}, number = {4}, pages = {1188-1204}, pmid = {37590829}, issn = {1538-6899}, mesh = {Humans ; *Neurodegenerative Diseases ; *Sleep Wake Disorders/complications/diagnosis ; *Parkinson Disease ; *Multiple Sclerosis ; *Stroke ; }, abstract = {OBJECTIVE: This article provides an overview of the growing body of evidence showing bidirectional relationships between sleep and various neurologic disorders.

LATEST DEVELOPMENTS: Mounting evidence demonstrates that disrupted sleep can negatively impact various neurologic disease processes, including stroke, multiple sclerosis, epilepsy, neuromuscular disorders including amyotrophic lateral sclerosis, and headache syndromes. Abnormal sleep can also be a precursor to Alzheimer disease and neurodegenerative disease states such as Parkinson disease and dementia with Lewy bodies. Interventions to improve sleep and treat obstructive sleep apnea may play a vital role in preventing neurologic disease development and progression.

ESSENTIAL POINTS: Sleep disorders are common among patients with neurologic disorders. To provide comprehensive care to patients with neurologic conditions, neurologists must ask patients about sleep issues that may warrant further diagnostic testing, treatment, and sleep medicine referral when indicated.}, } @article {pmid37590144, year = {2023}, author = {Hendricks, E and Quihuis, AM and Hung, ST and Chang, J and Dorjsuren, N and Der, B and Staats, KA and Shi, Y and Sta Maria, NS and Jacobs, RE and Ichida, JK}, title = {The C9ORF72 repeat expansion alters neurodevelopment.}, journal = {Cell reports}, volume = {42}, number = {8}, pages = {112983}, pmid = {37590144}, issn = {2211-1247}, support = {R00 NS077435/NS/NINDS NIH HHS/United States ; R01 NS097850/NS/NINDS NIH HHS/United States ; R44 NS097094/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Mice ; *Amyotrophic Lateral Sclerosis/genetics ; *C9orf72 Protein/genetics ; Dipeptides ; *Frontotemporal Dementia/genetics ; Mutation ; Disease Models, Animal ; }, abstract = {Genetic mutations that cause adult-onset neurodegenerative diseases are often expressed during embryonic stages, but it is unclear whether they alter neurodevelopment and how this might influence disease onset. Here, we show that the most common cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS), a repeat expansion in C9ORF72, restricts neural stem cell proliferation and reduces cortical and thalamic size in utero. Surprisingly, a repeat expansion-derived dipeptide repeat protein (DPR) not known to reduce neuronal viability plays a key role in impairing neurodevelopment. Pharmacologically mimicking the effects of the repeat expansion on neurodevelopment increases susceptibility of C9ORF72 mice to motor defects. Thus, the C9ORF72 repeat expansion stunts development of the brain regions prominently affected in C9ORF72 FTD/ALS patients.}, } @article {pmid37589710, year = {2023}, author = {Shu, L and Du, C and Zuo, Y}, title = {Abnormal phosphorylation of protein tyrosine in neurodegenerative diseases.}, journal = {Journal of neuropathology and experimental neurology}, volume = {82}, number = {10}, pages = {826-835}, doi = {10.1093/jnen/nlad066}, pmid = {37589710}, issn = {1554-6578}, mesh = {Humans ; Phosphorylation ; *Neurodegenerative Diseases/pathology ; Tyrosine/metabolism ; Signal Transduction ; Protein-Tyrosine Kinases ; Protein Tyrosine Phosphatases/metabolism ; }, abstract = {Neurodegenerative diseases, including Alzheimer disease, Parkinson disease, amyotrophic lateral sclerosis, and multiple sclerosis, are chronic disorders of the CNS that are characterized by progressive neuronal dysfunction. These diseases have diverse clinical and pathological features and their pathogenetic mechanisms are not yet fully understood. Currently, widely accepted hypotheses include the accumulation of misfolded proteins, oxidative stress from reactive oxygen species, mitochondrial dysfunction, DNA damage, neurotrophin dysfunction, and neuroinflammatory processes. In the CNS of patients with neurodegenerative diseases, a variety of abnormally phosphorylated proteins play important roles in pathological processes such as neuroinflammation and intracellular accumulation of β-amyloid plaques and tau. In recent years, the roles of abnormal tyrosine phosphorylation of intracellular signaling molecules regulated by protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs) in neurodegenerative diseases have attracted increasing attention. Here, we summarize the roles of signaling pathways related to protein tyrosine phosphorylation in the pathogenesis of neurodegenerative diseases and the progress of therapeutic studies targeting PTKs and PTPs that provide theoretical support for future studies on therapeutic strategies for these devastating and important neurodegenerative diseases.}, } @article {pmid37587694, year = {2023}, author = {Taylor, M and Marx, O and Norris, A}, title = {TDP-1 and FUST-1 co-inhibit exon inclusion and control fertility together with transcriptional regulation.}, journal = {Nucleic acids research}, volume = {51}, number = {18}, pages = {9610-9628}, pmid = {37587694}, issn = {1362-4962}, support = {R01 NS111055/NS/NINDS NIH HHS/United States ; R35GM133461/GM/NIGMS NIH HHS/United States ; R35 GM133461/GM/NIGMS NIH HHS/United States ; R01NS111055/NS/NINDS NIH HHS/United States ; /NH/NIH HHS/United States ; }, abstract = {Gene expression is a multistep process and crosstalk among regulatory layers plays an important role in coordinating gene expression. To identify functionally relevant gene expression coordination, we performed a systematic reverse-genetic interaction screen in C. elegans, combining RNA binding protein (RBP) and transcription factor (TF) mutants to generate over 100 RBP;TF double mutants. We identified many unexpected double mutant phenotypes, including two strong genetic interactions between the ALS-related RBPs, fust-1 and tdp-1, and the homeodomain TF ceh-14. Losing any one of these genes alone has no effect on the health of the organism. However, fust-1;ceh-14 and tdp-1;ceh-14 double mutants both exhibit strong temperature-sensitive fertility defects. Both double mutants exhibit defects in gonad morphology, sperm function, and oocyte function. RNA-Seq analysis of double mutants identifies ceh-14 as the main controller of transcript levels, while fust-1 and tdp-1 control splicing through a shared role in exon inhibition. A skipped exon in the polyglutamine-repeat protein pqn-41 is aberrantly included in tdp-1 mutants, and genetically forcing this exon to be skipped in tdp-1;ceh-14 double mutants rescues their fertility. Together our findings identify a novel shared physiological role for fust-1 and tdp-1 in promoting C. elegans fertility and a shared molecular role in exon inhibition.}, } @article {pmid37587387, year = {2023}, author = {Hamad, AA and Amer, BE and Al Mawla, AM and Goufa, E and Abdelwahab, MM and Serag, I}, title = {Clinical characteristics, course, and outcomes of amyotrophic lateral sclerosis overlapping with pregnancy: a systematic review of 38 published cases.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {44}, number = {12}, pages = {4219-4231}, pmid = {37587387}, issn = {1590-3478}, mesh = {Female ; Infant, Newborn ; Humans ; Pregnancy ; *Amyotrophic Lateral Sclerosis/complications/diagnosis ; *Neurodegenerative Diseases/complications ; Prognosis ; Health Status ; Databases, Factual ; }, abstract = {OBJECTIVES: Amyotrophic lateral sclerosis (ALS) is a rare and fatal neurodegenerative disease that can overlap with pregnancy, but little is known about its clinical characteristics, course, and outcomes in this context. This systematic review aimed to synthesize the current evidence on ALS overlapping with pregnancy.

METHODS: We comprehensively searched four databases on February 2, 2023, to identify case studies reporting cases of ALS overlapping with pregnancy. Joanna Brigs Institute tool was followed to assess the quality of the included studies.

RESULTS: Twenty-six articles reporting 38 cases were identified and included in our study. Out of the 38 cases, 18 were aged < 30 years. The onset of ALS was before pregnancy in 18 cases, during pregnancy in 16 cases, and directly after pregnancy in 4 cases. ALS progression course was rapid or severe in 55% of the cases during pregnancy, and this percentage reached 61% in cases with an onset of ALS before pregnancy. While ALS progression course after pregnancy was rapid or severe in 63% and stable in 37% of the cases. Most cases (95%) were able to complete the pregnancy and gave live birth. However, preterm delivery was common. For neonates, 86% were healthy without any complications.

CONCLUSION: While pregnancy with ALS is likely to survive and result in giving birth to healthy infants, it could be associated with rapid or severe progression of ALS and result in a worse prognosis, highlighting the importance of close monitoring and counselling for patients and healthcare providers.}, } @article {pmid37586842, year = {2024}, author = {Honda, H and Yagita, K and Arahata, H and Hamasaki, H and Noguchi, H and Koyama, S and Sasagasako, N}, title = {Increased expression of human antiviral protein MxA in FUS proteinopathy in amyotrophic lateral sclerosis.}, journal = {Brain pathology (Zurich, Switzerland)}, volume = {34}, number = {2}, pages = {e13191}, pmid = {37586842}, issn = {1750-3639}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/pathology ; Antiviral Agents/metabolism ; Mutation ; Neurons/pathology ; RNA-Binding Protein FUS/genetics ; }, abstract = {FUS mutations are one of the major mutations in familial amyotrophic lateral sclerosis (ALS). The pathological hallmark is FUS-positive neuronal cytoplasmic inclusions (FUS-NCI), known as FUS proteinopathy. Human myxovirus resistance protein 1 (MxA) is an IFN-induced dynamin-like GTPase that acts as antiviral factor. In this study, we examined the expression of MxA in neurons bearing FUS-NCI. We performed immunohistochemistry for FUS and MxA to examine the expression of MxA in two autopsy cases with different FUS gene mutations localized at the nuclear localization signal site (Case 1, H517P; Case 2, R521C). MxA. Most neurons bearing FUS-NCI have increased cytoplasmic MxA expression. Increased cytoplasmic MxA showed several distribution patterns in relation to FUS-NCIs such as the following: colocalization with NCI, distribution more widely than NCI, and different distribution peaks from NCI. Our results suggested that antiviral signaling IFNs are involved upstream in the formation of FUS-NCI in ALS-FUS patients.}, } @article {pmid37585529, year = {2023}, author = {Mann, JR and McKenna, ED and Mawrie, D and Papakis, V and Alessandrini, F and Anderson, EN and Mayers, R and Ball, HE and Kaspi, E and Lubinski, K and Baron, DM and Tellez, L and Landers, JE and Pandey, UB and Kiskinis, E}, title = {Loss of function of the ALS-associated NEK1 kinase disrupts microtubule homeostasis and nuclear import.}, journal = {Science advances}, volume = {9}, number = {33}, pages = {eadi5548}, pmid = {37585529}, issn = {2375-2548}, support = {R01 NS134166/NS/NINDS NIH HHS/United States ; R56 NS073873/NS/NINDS NIH HHS/United States ; I01 BX002466/BX/BLRD VA/United States ; P41 GM108569/GM/NIGMS NIH HHS/United States ; R01 NS073873/NS/NINDS NIH HHS/United States ; T32 AG020506/AG/NIA NIH HHS/United States ; P30 CA060553/CA/NCI NIH HHS/United States ; F31 NS117084/NS/NINDS NIH HHS/United States ; S10 OD025194/OD/NIH HHS/United States ; R01 NS104219/NS/NINDS NIH HHS/United States ; T32 NS041234/NS/NINDS NIH HHS/United States ; R21 NS107761/NS/NINDS NIH HHS/United States ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics ; Active Transport, Cell Nucleus ; NIMA-Related Kinase 1/genetics ; Proteins ; Motor Neurons ; Microtubules ; Homeostasis ; }, abstract = {Loss-of-function variants in NIMA-related kinase 1 (NEK1) constitute a major genetic cause of amyotrophic lateral sclerosis (ALS), accounting for 2 to 3% of all cases. However, how NEK1 mutations cause motor neuron (MN) dysfunction is unknown. Using mass spectrometry analyses for NEK1 interactors and NEK1-dependent expression changes, we find functional enrichment for proteins involved in the microtubule cytoskeleton and nucleocytoplasmic transport. We show that α-tubulin and importin-β1, two key proteins involved in these processes, are phosphorylated by NEK1 in vitro. NEK1 is essential for motor control and survival in Drosophila models in vivo, while using several induced pluripotent stem cell (iPSC)-MN models, including NEK1 knockdown, kinase inhibition, and a patient mutation, we find evidence for disruptions in microtubule homeostasis and nuclear import. Notably, stabilizing microtubules with two distinct classes of drugs restored NEK1-dependent deficits in both pathways. The capacity of NEK1 to modulate these processes that are critically involved in ALS pathophysiology renders this kinase a formidable therapeutic candidate.}, } @article {pmid37584401, year = {2023}, author = {Casiraghi, A and Gentile, A and Marjanovic, I and Chiò, A}, title = {Crushing riluzole tablets: evaluation of loss of powder and active principle in a home-simulation experiment.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {}, number = {}, pages = {1-7}, doi = {10.1080/21678421.2023.2245860}, pmid = {37584401}, issn = {2167-9223}, abstract = {Objective: Swallowing difficulties cause patients with amyotrophic lateral sclerosis (ALS) to crush oral medications, falling outside the labeling instructions and entailing some risks. To date, there is no evidence about consequences of crushing riluzole tablets in a home setting. This simulation experiment evaluated the loss of powder and active principle ingredient (API) mimicking the home setting with two alternative crushing methods (A and B). Methods: The tests were carried out by 15 volunteers without experience in the preparation of medication. Each volunteer manually crushed 5 tablets with a meat tenderizer (method A) or two spoons pressed against each other (method B). Riluzole was weighed before (W1) and after crushing (W2). Then, a subsample of crushed tablets was analyzed by HPLC to measure API content. The loss of powder was calculated as a percentage of the intact tablet weight, and the loss of API as a percentage of the labeled API content. Results: The quantitative analysis showed a mean percentage loss of 6.27% corresponding to a mean (SD) loss of powder of 13(±13) mg. The API loss was directly related to the powder loss: overall the mean percentage of API loss was 8.53% (corresponding to a mean API loss of 4.27 ± 4.50 mg). The difference in powder and API loss was highly statistically significant. Conclusion: Crushing riluzole tablets in a simulated home setting determined a significant loss of powder and API. These results support neurologists to evaluate formulations that minimize the need to alter the product and can improve ALS patient journey.}, } @article {pmid37584389, year = {2024}, author = {Liu, S and Sun, X and Ren, Q and Chen, Y and Dai, T and Yang, Y and Gong, G and Li, W and Zhao, Y and Meng, X and Lin, P and Yan, C}, title = {Glymphatic dysfunction in patients with early-stage amyotrophic lateral sclerosis.}, journal = {Brain : a journal of neurology}, volume = {147}, number = {1}, pages = {100-108}, doi = {10.1093/brain/awad274}, pmid = {37584389}, issn = {1460-2156}, support = {2020M672067//China Postdoctoral Science Foundation/ ; NSFC82001354//National Natural Science Foundation of China/ ; }, mesh = {Humans ; Animals ; Mice ; *Amyotrophic Lateral Sclerosis/complications ; Diffusion Tensor Imaging ; *Neurodegenerative Diseases ; Retrospective Studies ; Aquaporin 4 ; }, abstract = {Recently, an astrocytic aquaporin 4-dependent drainage system, that is, the glymphatic system, has been identified in the live murine and human brain. Growing evidence suggests that glymphatic function is impaired in patients with several neurodegenerative diseases, including Alzheimer's and Parkinson's disease. As the third most common neurodegenerative disease, although animal studies have indicated that early glymphatic dysfunction is likely an important pathological mechanism underpinning amyotrophic lateral sclerosis (ALS), no available study has been conducted to thoroughly assess glymphatic function in vivo in ALS patients to date, particularly in patients with early-stage ALS. Thus, using diffusion tensor imaging analysis along the perivascular space (ALPS) index, an approximate measure of glymphatic function in vivo, we aimed to explore whether glymphatic function is impaired in patients with patients with early-stage ALS, and the diagnostic performance of the ALPS index in distinguishing between patients with early-stage ALS and healthy subjects. We also aimed to identify the relationships between glymphatic dysfunction and clinical disabilities and sleep problems in patients with early-stage ALS. In this retrospective study, King's Stage 1 ALS patients were defined as patients with early-stage ALS. We enrolled 56 patients with early-stage ALS and 32 age- and sex-matched healthy control subjects. All participants completed clinical screening, sleep assessment and ALPS index analysis. For the sleep assessment, the Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale and polysomnography were used. Compared with healthy control subjects, patients with early-stage ALS had a significantly lower ALPS index after family-wise error correction (P < 0.05). Moreover, receiver operating characteristic analysis showed that the area under the curve for the ALPS index was 0.792 (95% confidence interval 0.700-0.884). Partial correlation analyses showed that the ALPS index was significantly correlated with clinical disability and sleep disturbances in patients with early-stage ALS. Multivariate analysis showed that sleep efficiency (r = 0.419, P = 0.002) and periodic limb movements in sleep index (r = -0.294, P = 0.017) were significant predictive factors of the ALPS index in patients with early-stage ALS. In conclusion, our study continues to support an important role for glymphatic dysfunction in ALS pathology, and we provide additional insights into the early diagnostic value of glymphatic dysfunction and its correlation with sleep disturbances in vivo in patients with early-stage ALS. Moreover, we suggest that early improvement of glymphatic function may be a promising strategy for slowing the neurodegenerative process in ALS. Future studies are needed to explore the diagnostic and therapeutic value of glymphatic dysfunction in individuals with presymptomatic-stage neurodegenerative diseases.}, } @article {pmid37582053, year = {2024}, author = {Assoni, AF and Guerrero, EN and Wardenaar, R and Oliveira, D and Bakker, PL and Alves, LM and Carvalho, VM and Okamoto, OK and Zatz, M and Foijer, F}, title = {IFNγ protects motor neurons from oxidative stress via enhanced global protein synthesis in FUS-associated amyotrophic lateral sclerosis.}, journal = {Brain pathology (Zurich, Switzerland)}, volume = {34}, number = {1}, pages = {e13206}, pmid = {37582053}, issn = {1750-3639}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/metabolism ; Motor Neurons/metabolism ; Mutation ; Oxidative Stress ; RNA-Binding Protein FUS/genetics ; }, abstract = {Amyotrophic lateral sclerosis type 6 (ALS6) is a familial subtype of ALS linked to Fused in Sarcoma (FUS) gene mutation. FUS mutations lead to decreased global protein synthesis, but the mechanism that drives this has not been established. Here, we used ALS6 patient-derived induced pluripotent stem cells (hIPSCs) to study the effect of the ALS6 FUS[R521H] mutation on the translation machinery in motor neurons (MNs). We find, in agreement with findings of others, that protein synthesis is decreased in FUS[R521H] MNs. Furthermore, FUS[R521H] MNs are more sensitive to oxidative stress and display reduced expression of TGF-β and mTORC gene pathways when stressed. Finally, we show that IFNγ treatment reduces apoptosis of FUS[R521H] MNs exposed to oxidative stress and partially restores the translation rates in FUS[R521H] MNs. Overall, these findings suggest that a functional IFNγ response is important for FUS-mediated protein synthesis, possibly by FUS nuclear translocation in ALS6.}, } @article {pmid37581600, year = {2023}, author = {Mehdipour, A and Teshler, L and Dal Bello-Haas, V and Richardson, J and Beauchamp, M and Turnbull, J and Chum, M and Johnston, W and O'Connell, C and Luth, W and Kuspinar, A}, title = {Assessing the Measurement Properties of the Self-Administered Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R): A Rasch Analysis.}, journal = {Physical therapy}, volume = {103}, number = {11}, pages = {}, doi = {10.1093/ptj/pzad109}, pmid = {37581600}, issn = {1538-6724}, support = {//ALS Society of Canada Project/ ; }, mesh = {Male ; Humans ; Middle Aged ; Female ; *Amyotrophic Lateral Sclerosis ; Reproducibility of Results ; Language ; Psychometrics ; Disease Progression ; }, abstract = {OBJECTIVE: The self-administered version of the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) is used to monitor function and disease progression in individuals with amyotrophic lateral sclerosis (ALS). However, the performance of the self-administered ALSFRS-R has not been assessed using Rasch Measurement Theory. Therefore, the purpose of this study was to examine the psychometric properties of the self-administered ALSFRS-R using Rasch analysis.

METHODS: Rasch analysis was performed on self-administered ALSFRS-R data from individuals with ALS across Canada. The following 6 aspects of Rasch analysis were examined using RUMM2030: fit via residuals and chi-square statistics, targeting via person-item threshold maps, dependency via item residual correlations, unidimensionality through principal components analysis of residuals, reliability via person separation index, and stability through differential item functioning analyses for sex, age, and language.

RESULTS: Analysis was performed on 122 participants (mean age: 52.9 years; 62.8% men). The overall scale demonstrated good fit, reliability, and stability; however, multidimensionality was found. To address this issue, items were divided into 3 subscales (bulbar, motor, and respiratory function), and Rasch analysis was performed for each subscale. The subscales demonstrated good fit, reliability, stability, and unidimensionality. However, there were still issues with item dependency for all subscale and targeting for bulbar and respiratory subscales.

CONCLUSIONS: The self-administered ALSFRS-R is reliable, internally valid, and stable across sex, age, and language subgroups; however, it is recommended that the ALSFRS-R be scored by subscale. Future studies can look at revising and/or adding items to tackle misfit, redundancy, and ceiling effects.

IMPACT: Self-administered measures are simple to administer and inexpensive. The self-administered ALSFRS-R was found to be psychometrically sound and can be used as a tool to monitor disease progression and function in ALS.}, } @article {pmid37581487, year = {2023}, author = {van Roon-Mom, W and Ferguson, C and Aartsma-Rus, A}, title = {From Failure to Meet the Clinical Endpoint to U.S. Food and Drug Administration Approval: 15th Antisense Oligonucleotide Therapy Approved Qalsody (Tofersen) for Treatment of SOD1 Mutated Amyotrophic Lateral Sclerosis.}, journal = {Nucleic acid therapeutics}, volume = {33}, number = {4}, pages = {234-237}, doi = {10.1089/nat.2023.0027}, pmid = {37581487}, issn = {2159-3345}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy/genetics ; Mutation ; *Oligonucleotides, Antisense/therapeutic use ; Superoxide Dismutase-1/genetics ; United States ; United States Food and Drug Administration ; Drug Approval ; Endpoint Determination ; }, } @article {pmid37581144, year = {2023}, author = {Risavi, BL and Carlson, J and Reese, EM and Raleigh, A and Wallis, J}, title = {Prehospital Surgical Airway Management Skills in a Rural Emergency Medical Service System.}, journal = {Cureus}, volume = {15}, number = {7}, pages = {e41864}, pmid = {37581144}, issn = {2168-8184}, abstract = {BACKGROUND: The objective of this study is to describe the education, training, and use of prehospital surgical airways in a rural Emergency Medical Service (EMS) system.

MATERIALS AND METHODS: We conducted an internet-based survey instrument of all advanced life support (ALS) EMS agencies in a seven-county rural EMS system in Pennsylvania. ALS agencies were queried regarding basic demographic information as well as the number of surgical airways performed in the previous 10 years as well as the education and training of EMS providers in surgical airways.

RESULTS: The survey was completed by 11 of 20 ALS EMS agencies in our region (55% rate of return). The content and frequency of training varied considerably among EMS agencies. Only four prehospital surgical airways were performed during the study period. One patient survived to hospital discharge to home.

CONCLUSION: Surgical airways are an infrequently performed procedure in the rural prehospital setting. There is no universally accepted standard for teaching or evaluating the competency of this potentially life-saving procedure. Further efforts to establish a core educational curriculum appear warranted.}, } @article {pmid37579999, year = {2023}, author = {Lin, S and Zhang, H and Qi, M and Cooper, DN and Yang, Y and Yang, Y and Zhao, H}, title = {Inferring the genetic relationship between brain imaging-derived phenotypes and risk of complex diseases by Mendelian randomization and genome-wide colocalization.}, journal = {NeuroImage}, volume = {279}, number = {}, pages = {120325}, doi = {10.1016/j.neuroimage.2023.120325}, pmid = {37579999}, issn = {1095-9572}, mesh = {Humans ; *Depressive Disorder, Major/diagnostic imaging/genetics ; *Cardiovascular Diseases/diagnostic imaging/genetics ; Genome-Wide Association Study/methods ; *Autism Spectrum Disorder/diagnostic imaging/genetics ; *Amyotrophic Lateral Sclerosis ; Mendelian Randomization Analysis/methods ; Phenotype ; *Brain Diseases/diagnostic imaging/genetics ; *Hypertension ; Neuroimaging ; }, abstract = {Observational studies consistently disclose brain imaging-derived phenotypes (IDPs) as critical markers for early diagnosis of both brain disorders and cardiovascular diseases. However, it remains unclear about the shared genetic landscape between brain IDPs and the risk of brain disorders and cardiovascular diseases, restricting the applications of potential diagnostic techniques through brain IDPs. Here, we reported genetic correlations and putative causal relationships between 921 brain IDPs, 20 brain disorders and six cardiovascular diseases by leveraging their large-scale genome-wide association study (GWAS) summary statistics. Applications of Mendelian randomization (MR) identified significant putative causal effects of multiple region-specific brain IDPs in relation to the increased risks for amyotrophic lateral sclerosis (ALS), major depressive disorder (MDD), autism spectrum disorder (ASD) and schizophrenia (SCZ). We also found brain IDPs specifically from temporal lobe as a putatively causal consequence of hypertension. The genome-wide colocalization analysis identified three genomic regions in which MDD, ASD and SCZ colocalized with the brain IDPs, and two novel SNPs to be associated with ASD, SCZ, and multiple brain IDPs. Furthermore, we identified a list of candidate genes involved in the shared genetics underlying pairs of brain IDPs and MDD, ASD, SCZ, ALS and hypertension. Our results provide novel insights into the genetic relationships between brain disorders and cardiovascular diseases and brain IDP, which may server as clues for using brain IDPs to predict risks of diseases.}, } @article {pmid37579835, year = {2023}, author = {Yadav, H and Jaldhi, and Bhardwaj, R and Anamika, and Bakshi, A and Gupta, S and Maurya, SK}, title = {Unveiling the role of gut-brain axis in regulating neurodegenerative diseases: A comprehensive review.}, journal = {Life sciences}, volume = {330}, number = {}, pages = {122022}, doi = {10.1016/j.lfs.2023.122022}, pmid = {37579835}, issn = {1879-0631}, mesh = {Humans ; *Neurodegenerative Diseases ; Brain-Gut Axis ; *Parkinson Disease/therapy ; *Gastrointestinal Microbiome/physiology ; *Probiotics/therapeutic use ; Brain ; }, abstract = {Emerging evidence have shown the importance of gut microbiota in regulating brain functions. The diverse molecular mechanisms involved in cross-talk between gut and brain provide insight into importance of this communication in maintenance of brain homeostasis. It has also been observed that disturbed gut microbiota contributes to neurological diseases such as Alzheimer's disease, Parkinson's disease, multiple sclerosis, amyotrophic lateral sclerosis and aging. Recently, gut microbiome-derived exosomes have also been reported to play an essential role in the development and progression of neurodegenerative diseases and could thereby act as a therapeutic target. Further, pharmacological interventions including antibiotics, prebiotics and probiotics can influence gut microbiome-mediated management of neurological diseases. However, extensive research is warranted to better comprehend this interconnection in maintenance of brain homeostasis and its implication in neurological diseases. Thus, the present review is aimed to provide a detailed understanding of gut-brain axis followed by possibilities to target the gut microbiome for improving neurological health.}, } @article {pmid37579155, year = {2023}, author = {Mohanty, P and Shenoy, J and Rizuan, A and Mercado-Ortiz, JF and Fawzi, NL and Mittal, J}, title = {A synergy between site-specific and transient interactions drives the phase separation of a disordered, low-complexity domain.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {120}, number = {34}, pages = {e2305625120}, pmid = {37579155}, issn = {1091-6490}, support = {R01 NS116176/NS/NINDS NIH HHS/United States ; }, mesh = {Humans ; Protein Domains ; *Amyotrophic Lateral Sclerosis/genetics/metabolism ; *Frontotemporal Dementia/genetics ; DNA-Binding Proteins/metabolism ; Methionine ; }, abstract = {TAR DNA-binding protein 43 (TDP-43) is involved in key processes in RNA metabolism and is frequently implicated in many neurodegenerative diseases, including amyotrophic lateral sclerosis and frontotemporal dementia. The prion-like, disordered C-terminal domain (CTD) of TDP-43 is aggregation-prone, can undergo liquid-liquid phase separation (LLPS) in isolation, and is critical for phase separation (PS) of the full-length protein under physiological conditions. While a short conserved helical region (CR, spanning residues 319-341) promotes oligomerization and is essential for LLPS, aromatic residues in the flanking disordered regions (QN-rich, IDR1/2) are also found to play a critical role in PS and aggregation. Compared with other phase-separating proteins, TDP-43 CTD has a notably distinct sequence composition including many aliphatic residues such as methionine and leucine. Aliphatic residues were previously suggested to modulate the apparent viscosity of the resulting phases, but their direct contribution toward CTD phase separation has been relatively ignored. Using multiscale simulations coupled with in vitro saturation concentration (csat) measurements, we identified the importance of aromatic residues while also suggesting an essential role for aliphatic methionine residues in promoting single-chain compaction and LLPS. Surprisingly, NMR experiments showed that transient interactions involving phenylalanine and methionine residues in the disordered flanking regions can directly enhance site-specific, CR-mediated intermolecular association. Overall, our work highlights an underappreciated mode of biomolecular recognition, wherein both transient and site-specific hydrophobic interactions act synergistically to drive the oligomerization and phase separation of a disordered, low-complexity domain.}, } @article {pmid37579081, year = {2023}, author = {Sulistyo, A and Abrahao, A and Freitas, ME and Ritsma, B and Zinman, L}, title = {Enteral tube feeding for amyotrophic lateral sclerosis/motor neuron disease.}, journal = {The Cochrane database of systematic reviews}, volume = {8}, number = {8}, pages = {CD004030}, pmid = {37579081}, issn = {1469-493X}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/complications/therapy ; *Deglutition Disorders/therapy/complications ; Enteral Nutrition/methods ; Intubation, Gastrointestinal ; *Motor Neuron Disease/complications ; }, abstract = {BACKGROUND: Maintaining adequate nutrition is critical for people with amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND). Enteral tube feeding is offered to people experiencing difficulty swallowing (dysphagia) to prevent weight loss and aspiration pneumonia. Among the types of enteral tube feeding, percutaneous endoscopic gastrostomy (PEG) is the typical procedure offered to people with ALS and will be mainly discussed here.

OBJECTIVES: To examine the effectiveness of percutaneous endoscopic gastrostomy or other enteral tube feeding in people with ALS, compared to oral feeds without enteral tube feeding on: 1. survival; 2. nutritional status; 3. quality of life. To examine the incidence of minor and major complications of percutaneous endoscopic gastrostomy (PEG) and other enteral tube feeding procedures in people with ALS.

SEARCH METHODS: On 3 January 2020 and 6 February 2021, we searched the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE. Embase, ClinicalTrials.gov and WHO ICTRP. We screened the results to identify randomized controlled studies on enteral tube feeding in ALS. We reviewed all references from the search in published articles to identify any additional references.

SELECTION CRITERIA: We included randomized controlled trials (RCTs), quasi-RCTs, and cross-over trials evaluating the effectiveness and complications of PEG or other enteral tube feeding placement in ALS.

DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane.

MAIN RESULTS: We found no RCTs or quasi-RCTs comparing the effectiveness of enteral tube feeding versus oral feeds without enteral tube feeding.

AUTHORS' CONCLUSIONS: There are no RCTs or quasi-RCTs to indicate whether enteral tube feeding is effective compared to continuation of oral feeding for any of the outcome measures. Such RCTs are very unlikely to be performed for ethical reasons. RCTs evaluating the effect of different enteral tube insertion techniques and timings of tube placement on survival and quality of life of people with ALS dysphagia are feasible and warranted.}, } @article {pmid37578398, year = {2024}, author = {Baskar, D and Veeramani-Kumar, P and Polavarapu, K and Nashi, S and Vengalil, S and Menon, D and Thomas, A and Bhargava Sanka, S and Muddasu Suhasini, K and Huddar, A and Unnikrishnan, G and Bardhan, M and Thomas, PT and Manjunath, N and Atchayaram, N}, title = {Clinical spectrum, biochemical profile and disease progression of Kennedy disease in an Indian cohort.}, journal = {Internal medicine journal}, volume = {54}, number = {3}, pages = {455-460}, doi = {10.1111/imj.16205}, pmid = {37578398}, issn = {1445-5994}, mesh = {Humans ; *Bulbo-Spinal Atrophy, X-Linked ; Retrospective Studies ; Disease Progression ; }, abstract = {BACKGROUND: Kennedy disease (KD) is a slowly progressive lower motor neuron degenerative disease. The prevalence of KD is unknown in India.

AIM: To describe the phenotypic and laboratory features of an Indian cohort of KD patients.

METHODS: A retrospective study was done on seven genetically confirmed KD patients based on demographic, clinical and laboratory details.

RESULTS: Mean age at onset and presentation was 37 ± 11.9 and 44.6 ± 13.5 years respectively. Progressive asymmetric proximal and distal limb weakness was the commonest symptom (57.1%). All patients had motor symptoms along with non-specific symptoms such as cramps from the onset. Easy fatigability, decremental response along with ptosis were noted in two patients, which was a novel finding. Gynaecomastia and tongue wasting with fasciculations were universal findings. All five patients with nerve conduction studies showed sensorimotor neuropathy. Magnetic resonance imaging muscle done in two patients showed a prominent moth-eaten appearance in the thigh and posterior leg compartment in one patient. The mean cytosine-adenine-guanine repeats were 44 ± 3.7, and there was no association between age of onset or severity with repeat length. Only one patient required an assistive device for ambulation after 15 years of symptom onset.

CONCLUSIONS: This study showed phenotypic heterogeneity in the Indian cohort. The age of onset was earlier with a slowly progressive indolent course as compared with other ethnic cohorts. This highlights the importance of considering the KD diagnosis in patients with the indolent course and suspected ALS diagnosis even with ptosis and fatigability in an appropriate clinical context.}, } @article {pmid37577689, year = {2023}, author = {Alvarado, CX and Weller, CA and Johnson, N and Leonard, HL and Singleton, AB and Reed, X and Blauewendraat, C and Nalls, M}, title = {Human brain single nucleus cell type enrichments in neurodegenerative diseases.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, pmid = {37577689}, abstract = {Single cell RNA sequencing has opened a window into clarifying the complex underpinnings of disease, particularly in quantifying the relevance of tissue- and cell-type-specific gene expression. To identify the cell types and genes important to therapeutic target development across the neurodegenerative disease spectrum, we leveraged genome-wide association studies, recent single cell sequencing data, and bulk expression studies in a diverse series of brain region tissues. We were able to identify significant immune-related cell types in the brain across three major neurodegenerative diseases: Alzheimer's Disease, Amyotrophic Lateral Sclerosis, and Parkinson's Diseases. Subsequently, we identified the major role of 30 fine-mapped loci implicating seven genes in multiple neurodegenerative diseases and their pathogenesis.}, } @article {pmid37577533, year = {2023}, author = {Duffy, MF and Ding, J and Langston, RG and Shah, SI and Nalls, MA and Scholz, SW and Whitaker, DT and Auluck, PK and Marenco, S and Gibbs, JR and Cookson, MR}, title = {Divergent patterns of healthy aging across human brain regions at single-cell resolution reveal links to neurodegenerative disease.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {37577533}, issn = {2692-8205}, support = {P30 AG050911/AG/NIA NIH HHS/United States ; ZIA AG000539/ImNIH/Intramural NIH HHS/United States ; ZIA NS003154/ImNIH/Intramural NIH HHS/United States ; }, abstract = {Age is a major common risk factor underlying neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. Previous studies reported that chronological age correlates with differential gene expression across different brain regions. However, prior datasets have not disambiguated whether expression associations with age are due to changes in cell numbers and/or gene expression per cell. In this study, we leveraged single nucleus RNA-sequencing (snRNAseq) to examine changes in cell proportions and transcriptomes in four different brain regions, each from 12 donors aged 20-30 years (young) or 60-85 years (old). We sampled 155,192 nuclei from two cortical regions (entorhinal cortex and middle temporal gyrus) and two subcortical regions (putamen and subventricular zone) relevant to neurodegenerative diseases or the proliferative niche. We found no changes in cellular composition of different brain regions with healthy aging. Surprisingly, we did find that each brain region has a distinct aging signature, with only minor overlap in differentially associated genes across regions. Moreover, each cell type shows distinct age-associated expression changes, including loss of protein synthesis genes in cortical inhibitory neurons, axonogenesis genes in excitatory neurons and oligodendrocyte precursor cells, enhanced gliosis markers in astrocytes and disease-associated markers in microglia, and genes critical for neuron-glia communication. Importantly, we find cell type-specific enrichments of age associations with genes nominated by Alzheimer's disease and Parkinson's disease genome-wide association studies (GWAS), such as apolipoprotein E (APOE), and leucine-rich repeat kinase 2 (LRRK2) in microglia that are independent of overall expression levels across cell types. We present this data as a new resource which highlights, first, region- and cell type-specific transcriptomic changes in healthy aging that may contribute to selective vulnerability and, second, provide context for testing GWAS-nominated disease risk genes in relevant subtypes and developing more targeted therapeutic strategies. The data is readily accessible without requirement for extensive computational support in a public website, https://brainexp-hykyffa56a-uc.a.run.app/.}, } @article {pmid37577380, year = {2023}, author = {Thompson, AG and Marsden, R and Talbot, K and Turner, MR}, title = {Primary care blood tests show lipid profile changes in pre-symptomatic amyotrophic lateral sclerosis.}, journal = {Brain communications}, volume = {5}, number = {4}, pages = {fcad211}, pmid = {37577380}, issn = {2632-1297}, support = {MR/T006927/1/MRC_/Medical Research Council/United Kingdom ; TURNER/OCT18/989-797/MNDA_/Motor Neurone Disease Association/United Kingdom ; }, abstract = {Multiple sources of evidence suggest that changes in metabolism may precede the onset of motor symptoms in amyotrophic lateral sclerosis. This study aimed to seek evidence for alterations in the levels of blood indices collected routinely in the primary care setting prior to the onset of motor symptoms in amyotrophic lateral sclerosis. Premorbid data, measured as part of routine health screening, for total cholesterol, high-density and low-density lipoprotein cholesterol, triglyceride, glycated haemoglobin A1c and creatinine were collected retrospectively from (i) a cohort of amyotrophic lateral sclerosis patients attending a specialist clinic (n = 143) and (ii) from primary care-linked data within UK Biobank. Data were fitted using linear mixed effects models with linear b-splines to identify inflection points, controlling for age and sex. In specialist amyotrophic lateral sclerosis clinic cases, models indicated decreasing levels of total and low-density lipoprotein cholesterol prior to an inflection point in the years before symptom onset (total cholesterol 3.25 years, low-density lipoprotein cholesterol 1.25 years), after which they stabilized or rose. A similar pattern was observed in amyotrophic lateral sclerosis cases within UK Biobank, occurring several years prior to diagnosis (total cholesterol 7 years, low-density lipoprotein cholesterol 7.25 years), differing significantly from matched controls. High-density lipoprotein cholesterol followed a similar pattern but was less robust to sensitivity analyses. Levels of triglyceride remained stable throughout. Glycated haemoglobin temporal profiles were not consistent between the clinic and biobank cohorts. Creatinine level trajectories prior to amyotrophic lateral sclerosis did not differ significantly from controls but decreased significantly in the symptomatic period after an inflection point of 0.25 years after symptom onset (clinic cohort) or 0.5 years before diagnosis (UK Biobank). These data provide further evidence for a pre-symptomatic period of dynamic metabolic change in amyotrophic lateral sclerosis, consistently associated with alterations in blood cholesterols. Such changes may ultimately contribute to biomarkers applicable to population screening and for pathways guiding the targeting of preventative therapy.}, } @article {pmid37576491, year = {2023}, author = {Seidel, M and Rajkumar, S and Steffke, C and Noeth, V and Agarwal, S and Roger, K and Lipecka, J and Ludolph, A and Guerrera, CI and Boeckers, T and Catanese, A}, title = {Propranolol reduces the accumulation of cytotoxic aggregates in C9orf72-ALS/FTD in vitro models.}, journal = {Current research in neurobiology}, volume = {5}, number = {}, pages = {100105}, pmid = {37576491}, issn = {2665-945X}, abstract = {Mutations in the C9orf72 gene are the most common cause of familial amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The pathogenetic mechanisms linked to this gene are a direct consequence of an aberrant intronic expansion of a GGGGCC hexanucleotide located between the 1a and 1b non-coding exons, which can be transcribed to form cytotoxic RNA foci or even translated into aggregation-prone dipeptide repeat proteins. Importantly, the abnormal length of these repeats affects also the expression levels of C9orf72 itself, which suggests haploinsufficiency as additional pathomechanism. Thus, it appears that both toxic gain of function and loss of function are distinct but still coexistent features contributing to the insurgence of the disease in case of C9orf72 mutations. In this study, we aimed at identifying a strategy to address both aspects of the C9orf72-related pathobiochemistry and provide proof-of-principle information for a better understanding of the mechanisms leading to neuronal loss. By using primary neurons overexpressing toxic poly(GA), the most abundant protein product of the GGGGCC repeats, we found that the antiarrhythmic drug propranolol could efficiently reduce the accumulation of aberrant aggregates and increase the survival of C9orf72-related cultures. Interestingly, the improved catabolism appeared to not depend on major degradative pathways such as autophagy and the proteasome. By analyzing the proteome of poly(GA)-expressing neurons after exposure to propranolol, we found that the drug increased lysosomal degradation through a mechanism directly involving C9orf72 protein, whose levels were increased after treatment. Further confirmation of the beneficial effect of the beta blocker on aggregates' accumulation and survival of hiPSC-derived C9orf72-mutant motoneurons strengthened the finding that addressing both facets of C9orf72 pathology might represent a valid strategy for the treatment of these ALS/FTD cases.}, } @article {pmid37576467, year = {2023}, author = {Yang, D and Wheeler, M and Karanth, SD and Aduse-Poku, L and Leeuwenburgh, C and Anton, S and Guo, Y and Bian, J and Liang, M and Yoon, HS and Akinyemiju, T and Braithwaite, D and Zhang, D}, title = {Allostatic load and risk of all-cause, cancer-specific, and cardiovascular mortality in older cancer survivors: an analysis of the National Health and Nutrition Examination Survey 1999-2010.}, journal = {Aging and cancer}, volume = {4}, number = {2}, pages = {74-84}, pmid = {37576467}, issn = {2643-8909}, support = {R01 CA249506/CA/NCI NIH HHS/United States ; }, abstract = {BACKGROUND: Allostatic load has been linked to an increased risk of death in various populations. However, to date, there is no research specifically investigating the effect of allostatic load on mortality in older cancer survivors.

AIMS: To investigate the association between allostatic load (AL) and mortality in older cancer survivors.

METHOD: A total of 1,291 adults aged 60 years or older who survived for ≥1 year since cancer diagnoses were identified from the 1999-2010 National Health and Nutrition Examination Survey. AL was the exposure of interest incorporating 9 clinical measures/biomarkers; one point was added to AL if any of the measures/biomarkers exceeded the normal level. The sum of points was categorized as an ordinal variable to reflect low, moderate, and high AL. Our outcomes of interest were all-cause, cancer-specific, and cardiovascular disease (CVD)-specific mortality. Death was identified by linkage to the National Death Index. Multivariable Cox proportional hazards models were used to estimate adjusted hazard ratio (aHR) and 95% confidence intervals (CI) of mortality by AL category.

RESULTS: Overall, 53.6% of participants were male and 78.4% were white. The mean age of study participants at interview was 72.8 years (SD=7.1). A total of 546 participants died during the follow-up (median follow-up time: 8.0 years). Among them, 158 died of cancer and 106 died of cardiovascular events. Results from multivariable Cox proportional hazards models showed that higher ALS was positively associated with higher all-cause mortality (ALS=4-9 vs. ALS =0-1: aHR=1.52, 95% CI =1.17-1.98, p-trend<0.01) and higher cancer-specific mortality (ALS=4-9 vs. ALS =0-1: aHR=1.80, 95% CI =1.12-2.90, p-trend=0.01). The association between ALS and cardiovascular mortality was positive but non-significant (ALS=4-9 vs. ALS =0-1: aHR=1.59, 95% CI =0.86-2.94, p-trend=0.11).

CONCLUSIONS: Our study suggests that older cancer survivors can have a higher risk of death if they have a high burden of AL.}, } @article {pmid37575992, year = {2023}, author = {Mohammadi, M and Yarmohammadi, A and Salehi-Abargouei, A and Ghasemirad, H and Shirvani, M and Ghoshouni, H}, title = {Uric acid and glaucoma: a systematic review and meta-analysis.}, journal = {Frontiers in medicine}, volume = {10}, number = {}, pages = {1159316}, pmid = {37575992}, issn = {2296-858X}, abstract = {BACKGROUND: Glaucoma, the leading cause of irreversible blindness, is a common disorder that contributes to gradual optic nerve degeneration. The beneficial impacts of uric acid (UA) have been reported in some neurodegenerative conditions such as Parkinson's disease, Alzheimer's disease, and amyotrophic lateral sclerosis. But the results of current studies about the association between serum UA level and glaucoma are conflicting. The present meta-analysis was conducted to provide a better understanding of the association between serum UA level and glaucoma.

METHODS: We searched the databases of PubMed, Scopus, Web of Science, and Google Scholar systematically until November 20, 2022 to identify case-control studies, comparing the serum UA concentrations of the patients with glaucoma and controls. The mean ± standard division difference was used to assess the difference in serum UA concentrations between the glaucoma patients and controls.

RESULTS: Six studies involving 1,221 glaucoma patients and 1,342 control group were included in the present meta-analysis. This meta-analysis using a random effect model indicated that the mean UA level in glaucoma patients was 0.13 (I[2] = 91.92%, 95% CI = -0.42 to 0.68) higher than the controls; however, it was not statistically significant.

CONCLUSIONS: Our findings provide evidence that glaucoma patients have a higher serum UA level compared to the controls, but this difference is not statistically significant. Prospective studies are needed to determine the possible association between increased UA and glaucoma pathogenesis.

https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022364055, identifier: CRD42022364055.}, } @article {pmid37575265, year = {2023}, author = {Clénet, ML and Keaney, J and Gillet, G and Valadas, JS and Langlois, J and Cardenas, A and Gasser, J and Kadiu, I}, title = {Divergent functional outcomes of NLRP3 blockade downstream of multi-inflammasome activation: therapeutic implications for ALS.}, journal = {Frontiers in immunology}, volume = {14}, number = {}, pages = {1190219}, pmid = {37575265}, issn = {1664-3224}, mesh = {Mice ; Animals ; Humans ; Inflammasomes/metabolism ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; *Amyotrophic Lateral Sclerosis/drug therapy/metabolism ; *Neurodegenerative Diseases ; NLR Proteins ; }, abstract = {NOD-Like Receptor Family Pyrin Domain Containing 3 (NLRP3) inflammasome modulation has emerged as a potential therapeutic approach targeting inflammation amplified by pyroptotic innate immune cell death. In diseases characterized by non-cell autonomous neurodegeneration including amyotrophic lateral sclerosis (ALS), the activation of several inflammasomes has been reported. Since functional redundancy can exist among inflammasome pathways, here we investigate the effects of NLRP3 inhibition on NLRP3, NLR family CARD Domain Containing 4 (NLRC4) and non-canonical pathways to understand whether NLRP3 blockade alone can mitigate pro-inflammatory cytokine release and pyroptotic cell death in contexts where single or multiple inflammasome pathways independent of NLRP3 are activated. In this study we do not limit our insights into inflammasome biology by solely relying on the THP-1 monocytic line under the LPS/nigericin-mediated NLRP3 pathway activation paradigm. We assess therapeutic potential and limitations of NLRP3 inhibition in multi-inflammasome activation contexts utilizing various human cellular systems including cell lines expressing gain of function (GoF) mutations for several inflammasomes, primary human monocytes, macrophages, healthy and Amyotrophic Lateral Sclerosis (ALS) patient induced pluripotent stem cells (iPSC)-derived microglia (iMGL) stimulated for canonical and non-canonical inflammasome pathways. We demonstrate that NLRP3 inhibition can modulate the NLRC4 and non-canonical inflammasome pathways; however, these effects differ between immortalized, human primary innate immune cells, and iMGL. We extend our investigation in more complex systems characterized by activation of multiple inflammasomes such as the SOD1[G93A] mouse model. Through deep immune phenotyping by single-cell mass cytometry we demonstrate that acute NLRP3 inhibition does not ameliorate spinal cord inflammation in this model. Taken together, our data suggests that NLRP3 inhibition alone may not be sufficient to address dynamic and complex neuroinflammatory pathobiological mechanisms including dysregulation of multiple inflammasome pathways in neurodegenerative disease such as ALS.}, } @article {pmid37575227, year = {2023}, author = {Terrabuio, E and Zenaro, E and Constantin, G}, title = {The role of the CD8+ T cell compartment in ageing and neurodegenerative disorders.}, journal = {Frontiers in immunology}, volume = {14}, number = {}, pages = {1233870}, pmid = {37575227}, issn = {1664-3224}, mesh = {Humans ; *CD8-Positive T-Lymphocytes ; Cytokines ; Central Nervous System ; *Amyotrophic Lateral Sclerosis ; }, abstract = {CD8+ lymphocytes are adaptive immunity cells with the particular function to directly kill the target cell following antigen recognition in the context of MHC class I. In addition, CD8+ T cells may release pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ), and a plethora of other cytokines and chemoattractants modulating immune and inflammatory responses. A role for CD8+ T cells has been suggested in aging and several diseases of the central nervous system (CNS), including Alzheimer's disease, Parkinson's disease, multiple sclerosis, amyotrophic lateral sclerosis, limbic encephalitis-induced temporal lobe epilepsy and Susac syndrome. Here we discuss the phenotypic and functional alterations of CD8+ T cell compartment during these conditions, highlighting similarities and differences between CNS disorders. Particularly, we describe the pathological changes in CD8+ T cell memory phenotypes emphasizing the role of senescence and exhaustion in promoting neuroinflammation and neurodegeneration. We also discuss the relevance of trafficking molecules such as selectins, mucins and integrins controlling the extravasation of CD8+ T cells into the CNS and promoting disease development. Finally, we discuss how CD8+ T cells may induce CNS tissue damage leading to neurodegeneration and suggest that targeting detrimental CD8+ T cells functions may have therapeutic effect in CNS disorders.}, } @article {pmid37573779, year = {2023}, author = {Zhang, Z and Zhu, Y and Zhu, C and Li, S and Zhao, Y and Yang, J and Qin, Y and Hou, J and Zhang, J and Han, C}, title = {Effects of Dihuang Yinzi Decoction on Alzheimer's Disease: A Systematic Review and Meta-Analysis.}, journal = {Complementary medicine research}, volume = {30}, number = {5}, pages = {440-452}, doi = {10.1159/000531931}, pmid = {37573779}, issn = {2504-2106}, mesh = {Humans ; *Alzheimer Disease/drug therapy ; Treatment Outcome ; *Medicine ; Medicine, Chinese Traditional ; China ; }, abstract = {OBJECTIVE: The aim of this study was to systematically evaluate the therapeutic effects of Dihuang Yinzi decoction on Alzheimer's disease (AD) and provide a medical evidence-based clinical application of traditional Chinese medicine (TCM).

METHODS: A comprehensive search was conducted across multiple databases, including PubMed, Embase, Cochrane Library, China National Journals Full-text Database, VIP Database for Chinese Technical Periodicals, Wan Fang database, and SinoMed database, to collect clinical randomized controlled trials of Dihuang Yinzi decoction in the treatment of AD. Strict literature screening was performed based on predefined inclusion and exclusion criteria. The Cochrane Collaboration risk of bias assessment tool and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system recommendation-level method was used to assess the quality of the included studies. Review Manager 5.4 and Stata 17 software were used for data synthesis and processing, while GRADE Profiler 3.6 software was used to evaluate the quality of evidence for outcome indicators (risk ratio, standardized mean difference, and weighted mean difference).

RESULTS: A total of 11 studies involving 798 patients met the inclusion criteria. Dihuang Yinzi decoction, whether used alone or in combination with conventional Western medicine, demonstrated superior efficacy compared to conventional Western medicine alone in improving the clinical effective rate, TCM syndrome score, activity of daily living score, Mini-Mental State Examination score, and Hasegawa Dementia Scale score in AD treatment. Furthermore, it exhibited a favorable safety profile. However, the GRADE evidence quality rating for the included studies was low.

CONCLUSIONS: Dihuang Yinzi decoction, either used alone or in combination with conventional Western medicine, shows promising results in enhancing cognitive and memory functions as well as the self-care ability of patients with AD. However, the low GRADE evidence quality rating highlights the need for focused advancements in the planning and execution of clinical randomized controlled trials during future research attempts.

UNLABELLED: ZIELZiel dieser Studie ist es, die therapeutischen Effekte von Dihuang Yinzi-Dekokt auf die Alzheimer-Krankheit systematisch zu bewerten und eine evidenzbasierte klinische Anwendung der traditionellen chinesischen Medizin (TCM) bereitzustellen.MethodenEs wurde eine umfassende Suche in mehreren Datenbanken, darunter PubMed, Embase, Cochrane Library, China National Journals Volltext-Datenbank, VIP Database for Chinese Technical Periodicals, Wan Fang Datenbank und SinoMed-Datenbank durchgeführt, um randomisierte, kontrollierte klinische Studien zu Dihuang Yinzi-Dekokt in der Behandlung der Alzheimer-Krankheit zu erfassen. Die strenge Literatursuche erfolgte auf Grundlage von vordefinierten Ein-und Ausschlusskriterien. Zur Bewertung der Qualität der eingeschlossenen Studien wurden das Risk-of-Bias-Tool von Cochrane und das GRADE (Grading of Recommendations Assessment, Development, and Evaluation)-System zur Beurteilung der Empfehlungsgrade herangezogen. Die Datensynthese und -verarbeitung erfolgten mithilfe der Review Manager 5.4- und der Stata 17-Software, während für die Bewertung der Evidenzqualität der Outcome-Indikatoren (Risikoverhältnis, standardisierte Mittelwertdifferenz und gewichtete Mittelwertdifferenz) die Software GRADE Profiler 3.6 verwendet wurde.ErgebnisseInsgesamt erfüllten 11 Studien, an denen 798 Patienten teilnahmen, die Einschlusskriterien. Dihuang Yinzi-Dekokt zeigte allein oder in Kombination mit konventioneller westlicher Medizin eine überlegene Wirksamkeit gegenüber der alleinigen Verwendung von konventioneller westlicher Medizin in Bezug auf die klinische Gesamtwirksamkeitsrate, den TCM-Syndrom-Score, den Score für die Alltagsaktivitäten, den Mini-Mental State Examination-Score und den Score der Hasegawa-Demenz-Skala in der Behandlung der Alzheimer-Krankheit. Darüber hinaus wies es ein günstiges Sicherheitsprofil auf. Die Evidenzqualität der eingeschlossenen Studien gemäß GRADE wurde jedoch als gering eingestuft.SchlussfolgerungenDihuang Yinzi-Dekokt zeigt allein oder in Kombination mit konventioneller westlicher Medizin vielversprechende Ergebnisse in Bezug auf die Verbesserung der kognitiven und Gedächtnisfunktionen sowie die Selbstversorgungsfähigkeit von Alzheimer-Patienten. Die niedrige Bewertung der Evidenzqualität gemäß GRADE unterstreicht jedoch die Notwendigkeit von zielgerichteten Weiterentwicklungen bei der Planung und Durchführung von randomisierten, kontrollierten klinischen Studien in zukünftigen Forschungsunternehmungen.}, } @article {pmid37573646, year = {2023}, author = {Kushol, R and Luk, CC and Dey, A and Benatar, M and Briemberg, H and Dionne, A and Dupré, N and Frayne, R and Genge, A and Gibson, S and Graham, SJ and Korngut, L and Seres, P and Welsh, RC and Wilman, AH and Zinman, L and Kalra, S and Yang, YH}, title = {SF2Former: Amyotrophic lateral sclerosis identification from multi-center MRI data using spatial and frequency fusion transformer.}, journal = {Computerized medical imaging and graphics : the official journal of the Computerized Medical Imaging Society}, volume = {108}, number = {}, pages = {102279}, doi = {10.1016/j.compmedimag.2023.102279}, pmid = {37573646}, issn = {1879-0771}, support = {//CIHR/Canada ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnostic imaging ; Canada ; Magnetic Resonance Imaging/methods ; Neuroimaging ; Brain/diagnostic imaging/pathology ; }, abstract = {Amyotrophic Lateral Sclerosis (ALS) is a complex neurodegenerative disorder characterized by motor neuron degeneration. Significant research has begun to establish brain magnetic resonance imaging (MRI) as a potential biomarker to diagnose and monitor the state of the disease. Deep learning has emerged as a prominent class of machine learning algorithms in computer vision and has shown successful applications in various medical image analysis tasks. However, deep learning methods applied to neuroimaging have not achieved superior performance in classifying ALS patients from healthy controls due to insignificant structural changes correlated with pathological features. Thus, a critical challenge in deep models is to identify discriminative features from limited training data. To address this challenge, this study introduces a framework called SF[2]Former, which leverages the power of the vision transformer architecture to distinguish ALS subjects from the control group by exploiting the long-range relationships among image features. Additionally, spatial and frequency domain information is combined to enhance the network's performance, as MRI scans are initially captured in the frequency domain and then converted to the spatial domain. The proposed framework is trained using a series of consecutive coronal slices and utilizes pre-trained weights from ImageNet through transfer learning. Finally, a majority voting scheme is employed on the coronal slices of each subject to generate the final classification decision. The proposed architecture is extensively evaluated with multi-modal neuroimaging data (i.e., T1-weighted, R2*, FLAIR) using two well-organized versions of the Canadian ALS Neuroimaging Consortium (CALSNIC) multi-center datasets. The experimental results demonstrate the superiority of the proposed strategy in terms of classification accuracy compared to several popular deep learning-based techniques.}, } @article {pmid37573553, year = {2023}, author = {Ling, YTT and Korneva, A and Quigley, HA and Nguyen, TD}, title = {Computational study of the mechanical behavior of the astrocyte network and axonal compartments in the mouse optic nerve head.}, journal = {Biomechanics and modeling in mechanobiology}, volume = {22}, number = {5}, pages = {1751-1772}, pmid = {37573553}, issn = {1617-7940}, support = {P30 EY001765/EY/NEI NIH HHS/United States ; R01 EY002120/EY/NEI NIH HHS/United States ; R56 EY002120/EY/NEI NIH HHS/United States ; EY 01765/NH/NIH HHS/United States ; }, mesh = {Mice ; Animals ; *Optic Disk ; Astrocytes ; *Glaucoma ; Intraocular Pressure ; Axons ; }, abstract = {Glaucoma is a blinding disease characterized by the degeneration of the retinal ganglion cell (RGC) axons at the optic nerve head (ONH). A major risk factor for glaucoma is the intraocular pressure (IOP). However, it is currently impossible to measure the IOP-induced mechanical response of the axons of the ONH. The objective of this study was to develop a computational modeling method to estimate the IOP-induced strains and stresses in the axonal compartments in the mouse astrocytic lamina (AL) of the ONH, and to investigate the effect of the structural features on the mechanical behavior. We developed experimentally informed finite element (FE) models of six mouse ALs to investigate the effect of structure on the strain responses of the astrocyte network and axonal compartments to pressure elevation. The specimen-specific geometries of the FE models were reconstructed from confocal fluorescent images of cryosections of the mouse AL acquired in a previous study that measured the structural features of the astrocytic processes and axonal compartments. The displacement fields obtained from digital volume correlation in prior inflation tests of the mouse AL were used to determine the displacement boundary conditions of the FE models. We then applied Gaussian process regression to analyze the effects of the structural features on the strain outcomes simulated for the axonal compartments. The axonal compartments experienced, on average, 6 times higher maximum principal strain but 1800 times lower maximum principal stress compared to those experienced by the astrocyte processes. The strains experienced by the axonal compartments were most sensitive to variations in the area of the axonal compartments. Larger axonal compartments that were more vertically aligned, closer to the AL center, and with lower local actin area fraction had higher strains. Understanding the factors affecting the deformation in the axonal compartments will provide insights into mechanisms of glaucomatous axonal damage.}, } @article {pmid37573101, year = {2023}, author = {Queral-Beltran, A and Marín-García, M and Lacorte, S and Tauler, R}, title = {UV-Vis absorption spectrophotometry and LC-DAD-MS-ESI(+)-ESI(-) coupled to chemometrics analysis of the monitoring of sulfamethoxazole degradation by chlorination, photodegradation, and chlorination/photodegradation.}, journal = {Analytica chimica acta}, volume = {1276}, number = {}, pages = {341563}, doi = {10.1016/j.aca.2023.341563}, pmid = {37573101}, issn = {1873-4324}, mesh = {*Sulfamethoxazole ; *Chemometrics ; Halogenation ; Photolysis ; Chlorine ; Spectrophotometry/methods ; Mass Spectrometry/methods ; Chromatography, Liquid ; }, abstract = {Sulfamethoxazole (SMX) is one of the most widely used antibiotics worldwide and has been detected at high concentrations in wastewater treatment plant effluents and river waters. In this study, the SMX degradation process combining the simultaneous chlorine oxidation and UV photodegradation is assessed and compared with both photodegradation and chlorine oxidation processes individually. Photodegradation and Chlorine/UV tests were performed using Suntest CPS equipment. Different experimental techniques, including UV-Visible spectrophotometry and liquid chromatography coupled to a diode array detector and positive and negative ionization mass spectrometry (LC-DAD-MS-ESI(+)-ESI(-)), were used to evaluate the degradation reaction of SMX. All the analytical data generated have been processed with the Multivariate Curve Resolution-Alternating Least Squares (MCR-ALS) method to monitor, resolve, and identify the several transformation products generated during the studied degradation processes. A new data fusion analysis strategy is proposed to examine the three processes simultaneously (with only photodegradation, only chlorination, and simultaneous chlorination+photodegradation). Combined with the analysis of different analytical techniques individually (spectrophotometry, LC-DAD, and LC-MS), the fusion of all generated data improved the description of the degradation processes. Detection using DAD allowed a better correspondence among the species monitored spectrophotometrically (UV-Vis) with those analyzed chromatographically. On the other side, detection using MS in both positive and negative acquisition modes allowed resolving a larger number of chemical compounds (specially SMX degradation subproducts) that could not be detected by UV-Vis spectrometry. The results obtained permitted the comparison of the effects produced by the three different degradation processes.}, } @article {pmid37572163, year = {2023}, author = {Teli, P and Kale, V and Vaidya, A}, title = {Beyond animal models: revolutionizing neurodegenerative disease modeling using 3D in vitro organoids, microfluidic chips, and bioprinting.}, journal = {Cell and tissue research}, volume = {394}, number = {1}, pages = {75-91}, pmid = {37572163}, issn = {1432-0878}, abstract = {Neurodegenerative diseases (NDs) are characterized by uncontrolled loss of neuronal cells leading to a progressive deterioration of brain functions. The transition rate of numerous neuroprotective drugs against Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease, leading to FDA approval, is only 8-14% in the last two decades. Thus, in spite of encouraging preclinical results, these drugs have failed in human clinical trials, demonstrating that traditional cell cultures and animal models cannot accurately replicate human pathophysiology. Hence, in vitro three-dimensional (3D) models have been developed to bridge the gap between human and animal studies. Such technological advancements in 3D culture systems, such as human-induced pluripotent stem cell (iPSC)-derived cells/organoids, organ-on-a-chip technique, and 3D bioprinting, have aided our understanding of the pathophysiology and underlying mechanisms of human NDs. Despite these recent advances, we still lack a 3D model that recapitulates all the key aspects of NDs, thus making it difficult to study the ND's etiology in-depth. Hence in this review, we propose developing a combinatorial approach that allows the integration of patient-derived iPSCs/organoids with 3D bioprinting and organ-on-a-chip technique as it would encompass the neuronal cells along with their niche. Such a 3D combinatorial approach would characterize pathological processes thoroughly, making them better suited for high-throughput drug screening and developing effective novel therapeutics targeting NDs.}, } @article {pmid37570984, year = {2023}, author = {Jin, R and Wang, J and Guo, B and Yang, T and Hu, J and Wang, B and Yu, Q}, title = {Identification and Expression Analysis of the Alfin-like Gene Family in Tomato and the Role of SlAL3 in Salt and Drought Stresses.}, journal = {Plants (Basel, Switzerland)}, volume = {12}, number = {15}, pages = {}, pmid = {37570984}, issn = {2223-7747}, support = {2022D01A269//Natural Science Foundation of Xinjiang Uygur Autonomous Region/ ; xjnkywdzc-2022001-8//Key Programs for Crop Important Traits Formation and Cutting-edge Technologies in Biological Breeding/ ; 2022B02002//Key Research and Development Task Special Project of Xinjiang Uygur Autonomous Region/ ; }, abstract = {Alfin-like (AL) transcription factors are a family of plant-specific genes with a PHD-finger-like structural domain at the C-terminus and a DUF3594 structural domain at the N-terminus that play important roles in plant development and stress response. In the present study, genome-wide identification and analysis were performed of the AL protein family in cultivated tomato (Solanum lycopersicum) and three wild relatives (S. pennellii, S. pimpinellifolium, and S. lycopersicoides) to evaluate their response to different abiotic stresses. A total of 39 ALs were identified and classified into four groups and based on phylogenetic tree and evolutionary analysis were shown to have formed prior to the differentiation of monocotyledons and dicots. Moreover, cis-acting element analysis revealed that various phytohormone response and abiotic stress response elements were highly existed in tomato. In addition, further analysis of the SlAL3 gene revealed that its expression was induced by drought and salt stresses and localized to the nucleus. In conclusion, our findings concerning AL genes provide useful information for further studies on their functions and regulatory mechanisms and provide theoretical references for studying AL gene response to abiotic stresses in plants.}, } @article {pmid37570771, year = {2023}, author = {Liu, X and Zhao, X and He, J and Wang, S and Shen, X and Liu, Q and Wang, S}, title = {Advances in the Structure of GGGGCC Repeat RNA Sequence and Its Interaction with Small Molecules and Protein Partners.}, journal = {Molecules (Basel, Switzerland)}, volume = {28}, number = {15}, pages = {}, pmid = {37570771}, issn = {1420-3049}, support = {22274050//National Natural Science Foundation of China/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism ; *Frontotemporal Dementia/genetics ; Base Sequence ; DNA Repeat Expansion ; RNA/genetics/chemistry ; RNA-Binding Proteins/genetics/metabolism ; }, abstract = {The aberrant expansion of GGGGCC hexanucleotide repeats within the first intron of the C9orf72 gene represent the predominant genetic etiology underlying amyotrophic lateral sclerosis (ALS) and frontal temporal dementia (FTD). The transcribed r(GGGGCC)n RNA repeats form RNA foci, which recruit RNA binding proteins and impede their normal cellular functions, ultimately resulting in fatal neurodegenerative disorders. Furthermore, the non-canonical translation of the r(GGGGCC)n sequence can generate dipeptide repeats, which have been postulated as pathological causes. Comprehensive structural analyses of r(GGGGCC)n have unveiled its polymorphic nature, exhibiting the propensity to adopt dimeric, hairpin, or G-quadruplex conformations, all of which possess the capacity to interact with RNA binding proteins. Small molecules capable of binding to r(GGGGCC)n have been discovered and proposed as potential lead compounds for the treatment of ALS and FTD. Some of these molecules function in preventing RNA-protein interactions or impeding the phase transition of r(GGGGCC)n. In this review, we present a comprehensive summary of the recent advancements in the structural characterization of r(GGGGCC)n, its propensity to form RNA foci, and its interactions with small molecules and proteins. Specifically, we emphasize the structural diversity of r(GGGGCC)n and its influence on partner binding. Given the crucial role of r(GGGGCC)n in the pathogenesis of ALS and FTD, the primary objective of this review is to facilitate the development of therapeutic interventions targeting r(GGGGCC)n RNA.}, } @article {pmid37569549, year = {2023}, author = {Yabata, H and Riku, Y and Miyahara, H and Akagi, A and Sone, J and Urushitani, M and Yoshida, M and Iwasaki, Y}, title = {Nuclear Expression of TDP-43 Is Linked with Morphology and Ubiquitylation of Cytoplasmic Aggregates in Amyotrophic Lateral Sclerosis.}, journal = {International journal of molecular sciences}, volume = {24}, number = {15}, pages = {}, pmid = {37569549}, issn = {1422-0067}, support = {JP20K16586, JP22K07359, JP23K06935//JSPS KAKENHI/ ; JP20ek0109392, JP20ek0109391//AMED/ ; (30-8)//Intramural Research Grant for Neurological and Psychiatric Disorders of NCNP/ ; not applicable//Grants-in-Aid from the Research Committee of CNS Degenerative Diseases, Research on Policy Planning and Evaluation for Rare and Intractable Diseases, Health, Labour, and Welfare Sciences Research Grants, the Ministry of Health, Labour, and Welfare, Japan/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism ; DNA-Binding Proteins/metabolism ; Motor Neurons/metabolism ; Ubiquitination ; }, abstract = {The transactive response DNA-binding protein of 43 kDa (TDP-43) is a pathological protein of amyotrophic lateral sclerosis (ALS). TDP-43 pathology is characterized by a combination of the cytoplasmic aggregation and nuclear clearance of this protein. However, the mechanisms underlying TDP-43 pathology have not been fully clarified. The aim of this study was to evaluate the relationships between the expression level of nuclear TDP-43 and the pathological properties of cytoplasmic aggregates in autopsied ALS cases. We included 22 consecutively autopsied cases with sporadic TDP-43-related ALS. The motor neuron systems were neuropathologically assessed. We identified 790 neurons with cytoplasmic TDP-43 inclusions from the lower motor neuron system of included cases. Nuclear TDP-43 disappeared in 84% (n = 660) and expressed in 16% (n = 130) of neurons with cytoplasmic inclusions; the former was defined as TDP-43 cytoplasmic immunoreactivity (c-ir), and the latter was defined as nuclear and cytoplasmic immunoreactivity (n/c-ir). Morphologically, diffuse cytoplasmic inclusions were significantly more prevalent in TDP-43 n/c-ir neurons than in c-ir neurons, while skein-like and round inclusions were less prevalent in n/c-ir neurons. The cytoplasmic inclusions of TDP-43 n/c-ir neurons were phosphorylated but poorly ubiquitylated when compared with those of c-ir neurons. TDP-43 n/c-ir neurons became less dominant than the c-ir neurons among cases with a prolonged disease duration. The expression level of nuclear TDP-43 was significantly lower in n/c-ir neurons than in normal neurons without cytoplasmic inclusions. Our results indicate that the maturation of cytoplasmic TDP-43 inclusions correlates with the depletion of nuclear TDP-43 in each affected neuron. This finding supports the view that an imbalance between nuclear and cytoplasmic TDP-43 may be an essential pathway to TDP-43 pathology.}, } @article {pmid37569475, year = {2023}, author = {Napoli, G and Rubin, M and Cutillo, G and Schito, P and Russo, T and Quattrini, A and Filippi, M and Riva, N}, title = {Tako-Tsubo Syndrome in Amyotrophic Lateral Sclerosis: Single-Center Case Series and Brief Literature Review.}, journal = {International journal of molecular sciences}, volume = {24}, number = {15}, pages = {}, pmid = {37569475}, issn = {1422-0067}, support = {Percorso Marazzina//Giovanni Marazzina Foundation/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/complications ; *Takotsubo Cardiomyopathy/complications ; *Neurodegenerative Diseases/complications ; Retrospective Studies ; *Primary Dysautonomias ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with variable phenotypic expressions which has been associated with autonomic dysfunction. The cardiovascular system seems to be affected especially in the context of bulbar involvement. We describe four new cases of Tako-Tsubo syndrome (TTS) in ALS patients with an appraisal of the literature. We present a late-stage ALS patient with prominent bulbar involvement that presented TTS during hospitalization. We then retrospectively identify three additional ALS-TTS cases reporting relevant clinical findings. TTS cardiomyopathy has been observed in different acute neurological conditions, and the co-occurrence of ALS and TTS has already been reported. Cardiovascular autonomic dysfunctions have been described in ALS, especially in the context of an advanced diseases and with bulbar involvement. Noradrenergic hyperfunction linked to sympathetic denervation and ventilatory deficits coupled in different instances with a trigger event could play a synergistic role in the development of TTS in ALS. Sympathetic hyperfunctioning and ventilatory deficits in conjunction with cardiac autonomic nerves impairment may play a role in the development of TTS in a context of ALS.}, } @article {pmid37568457, year = {2023}, author = {Boentert, M and Hermann, A and Großkreutz, J}, title = {Amyotrophic Lateral Sclerosis: Advances and Prospects.}, journal = {Journal of clinical medicine}, volume = {12}, number = {15}, pages = {}, pmid = {37568457}, issn = {2077-0383}, abstract = {The JCM Topical Collection "Amyotrophic Lateral Sclerosis: Latest Advances and Prospects" started in 2020 and currently includes 11 publications reflecting a broad range of clinical research areas in the ALS field [...].}, } @article {pmid37568439, year = {2023}, author = {Risi, B and Cotti Piccinelli, S and Gazzina, S and Labella, B and Caria, F and Damioli, S and Poli, L and Padovani, A and Filosto, M}, title = {Prognostic Usefulness of Motor Unit Number Index (MUNIX) in Patients Newly Diagnosed with Amyotrophic Lateral Sclerosis.}, journal = {Journal of clinical medicine}, volume = {12}, number = {15}, pages = {}, pmid = {37568439}, issn = {2077-0383}, abstract = {UNLABELLED: The MUNIX technique allows us to estimate the number and size of surviving motor units (MUs). Previous studies on ALS found correlations between MUNIX and several clinical measures, but its potential role as a predictor of disease progression rate (DPR) has not been thoroughly evaluated to date. We aimed to investigate MUNIX's ability to predict DPR at a six-month follow up.

METHODS: 24 ALS patients with short disease duration (<24 months from symptoms' onset) were enrolled and divided according to their baseline DPR into two groups (normal [DPR-N] and fast [DPR-F] progressors). MUNIX values were obtained from five muscles (TA, APB, ADM, FDI, Trapezius) and averaged for each subject.

RESULTS: MUNIX was found to predict DPR at follow up in a multivariable linear regression model; namely, patients with lower MUNIX values were at risk of showing greater DPR scores at follow up. The result was replicated in a simple logistic regression analysis, with the dichotomic category "MUNIX-Low" as the independent variable and the outcome "DPR-F" as the dependent variable.

CONCLUSIONS: our results pave the way for the use of the MUNIX method as a prognostic tool in early ALS, enabling patients' stratification according to their rates of future decline.}, } @article {pmid37567819, year = {2024}, author = {Marrie, RA and Maxwell, CJ and Rotstein, DL and Tsai, CC and Tremlett, H}, title = {Prodromes in demyelinating disorders, amyotrophic lateral sclerosis, Parkinson disease, and Alzheimer's dementia.}, journal = {Revue neurologique}, volume = {180}, number = {3}, pages = {125-140}, doi = {10.1016/j.neurol.2023.07.002}, pmid = {37567819}, issn = {0035-3787}, mesh = {Humans ; *Alzheimer Disease/diagnosis ; *Parkinson Disease/complications/diagnosis ; *Amyotrophic Lateral Sclerosis/diagnosis ; Biomarkers ; *Multiple Sclerosis ; Prodromal Symptoms ; }, abstract = {A prodrome is an early set of symptoms, which indicates the onset of a disease; these symptoms are often non-specific. Prodromal phases are now recognized in multiple central nervous system diseases. The depth of understanding of the prodromal phase varies across diseases, being more nascent for multiple sclerosis for example, than for Parkinson disease or Alzheimer's disease. Key challenges when identifying the prodromal phase of a disease include the lack of specificity of prodromal symptoms, and consequent need for accessible and informative biomarkers. Further, heterogeneity of the prodromal phase may be influenced by age, sex, genetics and other poorly understood factors. Nonetheless, recognition that an individual is in the prodromal phase of disease offers the opportunity for earlier diagnosis and with it the opportunity for earlier intervention.}, } @article {pmid37567224, year = {2023}, author = {Takano, HK and Benko, ZL and Zielinski, MM and Hamza, A and Kalnmals, CA and Roth, JJ and Bravo-Altamirano, K and Siddall, T and Satchivi, N and Church, JB and Riar, DS}, title = {Discovery and Mode-of-Action Characterization of a New Class of Acetolactate Synthase-Inhibiting Herbicides.}, journal = {Journal of agricultural and food chemistry}, volume = {71}, number = {47}, pages = {18227-18238}, doi = {10.1021/acs.jafc.3c03858}, pmid = {37567224}, issn = {1520-5118}, mesh = {*Herbicides/pharmacology/chemistry ; *Acetolactate Synthase/chemistry ; Herbicide Resistance ; Ethers ; }, abstract = {Herbicides are effective tools to manage weeds and enable food production and sustainable agriculture. Corteva Agriscience R&D has recently discovered new diphenyl-ether compounds displaying excellent postemergent efficacy on important weed species along with corn safety. Here, we describe the chemistry, biology, biochemistry, and computational modeling research that led to the discovery and elucidation of the primary mode of action for these compounds. The target protein was found to be acetolactate synthase (ALS), a key enzyme in the biosynthesis of branched chain amino acids (valine, leucine, and isoleucine). While weed resistance evolution to ALS herbicides is widespread, the molecular interaction of the diphenyl-ether compounds at the active site of the ALS enzyme differs significantly from that of some commercial ALS inhibitors. The unique biochemical profile of these molecules along with their excellent herbicidal activity and corn selectivity make them a noteworthy development in the pursuit of novel, safe, and sustainable weed control solutions.}, } @article {pmid37566385, year = {2023}, author = {Kreple, CJ and Gajagowni, S and Jockel-Balsaratti, J and Bucelli, RC and Miller, TM}, title = {Lumbar punctures are safe in patients with ALS and have a risk profile similar to that in the non-ALS population.}, journal = {Muscle & nerve}, volume = {68}, number = {5}, pages = {771-775}, doi = {10.1002/mus.27956}, pmid = {37566385}, issn = {1097-4598}, support = {R01NS097816/NH/NIH HHS/United States ; R01NS078398/NH/NIH HHS/United States ; R01NS097816/NH/NIH HHS/United States ; R01NS078398/NH/NIH HHS/United States ; }, abstract = {INTRODUCTION/AIMS: Analysis of biofluids, especially cerebrospinal fluid (CSF), is critically important for amyotrophic lateral sclerosis (ALS) research. Collection of CSF is typically performed by lumbar puncture (LP). Previous studies have demonstrated the safety of LPs in patients with other neurodegenerative diseases, such as Alzheimer's disease, although there are no published studies of the safety of LPs in patients with ALS. We performed a retrospective analysis of complications resulting from LPs.

METHODS: This is a retrospective study of LPs performed between 2015 and 2021 on a total of 233 participants (healthy controls [n = 63], ALS [n = 154], and disease controls [n = 16]) as part of clinical research studies at the Washington University ALS Center. We used bivariate logistical analyses looking for associations between participant characteristics and adverse events (AEs), and likelihood ratio tests were used for significance testing.

RESULTS: We found an overall AE rate of 21.03%. AEs included headache, back pain, vasovagal syncope, and severe headache requiring epidural blood patch. Participants with ALS were not more likely to experience post-LP AEs compared to controls (odds ratio [OR] 0.61 [0.32-1.18]). Post-LP headaches were significantly less likely in participants with ALS (OR 0.36 [0.15-0.83]).

DISCUSSION: Our findings demonstrate that LP is a safe procedure for participants with ALS, with a similar or lower rate of AEs than in participants without ALS.}, } @article {pmid37566177, year = {2024}, author = {Meyer, M and Meijer, O and Hunt, H and Belanoff, J and Lima, A and de Kloet, ER and Gonzalez Deniselle, MC and De Nicola, AF}, title = {Stress-induced Neuroinflammation of the Spinal Cord is Restrained by Cort113176 (Dazucorilant), A Specific Glucocorticoid Receptor Modulator.}, journal = {Molecular neurobiology}, volume = {61}, number = {1}, pages = {1-14}, pmid = {37566177}, issn = {1559-1182}, support = {PIP 11220170100002CO//Consejo Nacional de Investigaciones Científicas y Técnicas/ ; PIP 11220210100091CO//Consejo Nacional de Investigaciones Científicas y Técnicas/ ; PICT 2021 00389//Ministerio de Ciencia, Tecnología e Innovación Productiva/ ; Ubacyt 20020170100224BA//Secretaria de Ciencia y Tecnica, Universidad de Buenos Aires/ ; }, mesh = {Male ; Mice ; Humans ; Animals ; Receptors, Glucocorticoid/metabolism ; Corticosterone ; *HMGB1 Protein/metabolism ; Neuroinflammatory Diseases ; Gliosis/metabolism ; Toll-Like Receptor 4/metabolism ; Glucocorticoids/pharmacology ; Spinal Cord/metabolism ; *Neurodegenerative Diseases/metabolism ; *Isoquinolines ; *Pyrazoles ; }, abstract = {Glucocorticoids exert antiinflammatory, antiproliferative and immunosupressive effects. Paradoxically they may also enhance inflammation particularly in the nervous system, as shown in Cushing´ syndrome and neurodegenerative disorders of humans and models of human diseases. ."The Wobbler mouse model of amyotrophic lateral sclerosis shows hypercorticoidism and neuroinflammation which subsided by treatment with the glucocorticoid receptor (GR) modulator Dazucorilant (CORT113176). This effect suggests that GR mediates the chronic glucocorticoid unwanted effects. We now tested this hypothesis using a chronic stress model resembling the condition of the Wobbler mouse Male NFR/NFR mice remained as controls or were subjected to a restraining / rotation stress protocol for 3 weeks, with a group of stressed mice receiving CORT113176 also for 3 weeks. We determined the mRNAS or reactive protein for the proinflamatory factors HMGB1, TLR4, NFkB, TNFα, markers of astrogliosis (GFAP, SOX9 and acquaporin 4), of microgliosis (Iba, CD11b, P2RY12 purinergic receptor) as well as serum IL1β and corticosterone. We showed that chronic stress produced high levels of serum corticosterone and IL1β, decreased body and spleen weight, produced microgliosis and astrogliosis and increased proinflammatory mediators. In stressed mice, modulation of the GR with CORT113176 reduced Iba + microgliosis, CD11b and P2RY12 mRNAs, immunoreactive HMGB1 + cells, GFAP + astrogliosis, SOX9 and acquaporin expression and TLR4 and NFkB mRNAs vs. stress-only mice. The effects of CORT113176 indicate that glucocorticoids are probably involved in neuroinflammation. Thus, modulation of the GR would become useful to dampen the inflammatory component of neurodegenerative disorders.}, } @article {pmid37566088, year = {2023}, author = {Rossi, S and Di Salvio, M and Balì, M and De Simone, A and Apolloni, S and D'Ambrosi, N and Arisi, I and Cipressa, F and Cozzolino, M and Cestra, G}, title = {C9orf72 Toxic Species Affect ArfGAP-1 Function.}, journal = {Cells}, volume = {12}, number = {15}, pages = {}, pmid = {37566088}, issn = {2073-4409}, mesh = {Animals ; Humans ; Mice ; ADP-Ribosylation Factor 1/metabolism ; *Amyotrophic Lateral Sclerosis/metabolism ; *C9orf72 Protein/genetics/metabolism ; Drosophila/genetics/metabolism ; RNA/metabolism ; RNA, Messenger/genetics ; *GTPase-Activating Proteins/genetics/metabolism ; }, abstract = {Compelling evidence indicates that defects in nucleocytoplasmic transport contribute to the pathogenesis of amyotrophic lateral sclerosis (ALS). In particular, hexanucleotide (G4C2) repeat expansions in C9orf72, the most common cause of genetic ALS, have a widespread impact on the transport machinery that regulates the nucleocytoplasmic distribution of proteins and RNAs. We previously reported that the expression of G4C2 hexanucleotide repeats in cultured human and mouse cells caused a marked accumulation of poly(A) mRNAs in the cell nuclei. To further characterize the process, we set out to systematically identify the specific mRNAs that are altered in their nucleocytoplasmic distribution in the presence of C9orf72-ALS RNA repeats. Interestingly, pathway analysis showed that the mRNAs involved in membrane trafficking are particularly enriched among the identified mRNAs. Most importantly, functional studies in cultured cells and Drosophila indicated that C9orf72 toxic species affect the membrane trafficking route regulated by ADP-Ribosylation Factor 1 GTPase Activating Protein (ArfGAP-1), which exerts its GTPase-activating function on the small GTPase ADP-ribosylation factor 1 to dissociate coat proteins from Golgi-derived vesicles. We demonstrate that the function of ArfGAP-1 is specifically affected by expanded C9orf72 RNA repeats, as well as by C9orf72-related dipeptide repeat proteins (C9-DPRs), indicating the retrograde Golgi-to-ER vesicle-mediated transport as a target of C9orf72 toxicity.}, } @article {pmid37566031, year = {2023}, author = {Torazza, C and Provenzano, F and Gallia, E and Cerminara, M and Balbi, M and Bonifacino, T and Tessitore, S and Ravera, S and Usai, C and Musante, I and Puliti, A and Van Den Bosch, L and Jafar-Nejad, P and Rigo, F and Milanese, M and Bonanno, G}, title = {Genetic Downregulation of the Metabotropic Glutamate Receptor Type 5 Dampens the Reactive and Neurotoxic Phenotype of Adult ALS Astrocytes.}, journal = {Cells}, volume = {12}, number = {15}, pages = {}, pmid = {37566031}, issn = {2073-4409}, mesh = {Animals ; Mice ; *Amyotrophic Lateral Sclerosis/metabolism ; Astrocytes/metabolism ; Down-Regulation/genetics ; Glutamic Acid/metabolism ; Mice, Transgenic ; *Neurodegenerative Diseases/metabolism ; Superoxide Dismutase-1/genetics/metabolism ; *Receptor, Metabotropic Glutamate 5/genetics ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive degeneration of motor neurons (MNs). Astrocytes display a toxic phenotype in ALS, which results in MN damage. Glutamate (Glu)-mediated excitotoxicity and group I metabotropic glutamate receptors (mGluRs) play a pathological role in the disease progression. We previously demonstrated that in vivo genetic ablation or pharmacological modulation of mGluR5 reduced astrocyte activation and MN death, prolonged survival and ameliorated the clinical progression in the SOD1[G93A] mouse model of ALS. This study aimed to investigate in vitro the effects of mGluR5 downregulation on the reactive spinal cord astrocytes cultured from adult late symptomatic SOD1[G93A] mice. We observed that mGluR5 downregulation in SOD1[G93A] astrocytes diminished the cytosolic Ca[2+] overload under resting conditions and after mGluR5 simulation and reduced the expression of the reactive glial markers GFAP, S100β and vimentin. In vitro exposure to an anti-mGluR5 antisense oligonucleotide or to the negative allosteric modulator CTEP also ameliorated the altered reactive astrocyte phenotype. Downregulating mGluR5 in SOD1[G93A] mice reduced the synthesis and release of the pro-inflammatory cytokines IL-1β, IL-6 and TNF-α and ameliorated the cellular bioenergetic profile by improving the diminished oxygen consumption and ATP synthesis and by lowering the excessive lactate dehydrogenase activity. Most relevantly, mGluR5 downregulation hampered the neurotoxicity of SOD1[G93A] astrocytes co-cultured with spinal cord MNs. We conclude that selective reduction in mGluR5 expression in SOD1[G93A] astrocytes positively modulates the astrocyte reactive phenotype and neurotoxicity towards MNs, further supporting mGluR5 as a promising therapeutic target in ALS.}, } @article {pmid37566027, year = {2023}, author = {Bagyinszky, E and Hulme, J and An, SSA}, title = {Studies of Genetic and Proteomic Risk Factors of Amyotrophic Lateral Sclerosis Inspire Biomarker Development and Gene Therapy.}, journal = {Cells}, volume = {12}, number = {15}, pages = {}, pmid = {37566027}, issn = {2073-4409}, mesh = {Humans ; Child ; *Amyotrophic Lateral Sclerosis/genetics/therapy/metabolism ; *Neurodegenerative Diseases ; Proteomics ; DNA-Binding Proteins/metabolism ; Superoxide Dismutase-1 ; Biomarkers ; Risk Factors ; DNA Helicases ; RNA Helicases ; Multifunctional Enzymes ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease affecting the upper and lower motor neurons, leading to muscle weakness, motor impairments, disabilities and death. Approximately 5-10% of ALS cases are associated with positive family history (familial ALS or fALS), whilst the remainder are sporadic (sporadic ALS, sALS). At least 50 genes have been identified as causative or risk factors for ALS. Established pathogenic variants include superoxide dismutase type 1 (SOD1), chromosome 9 open reading frame 72 (c9orf72), TAR DNA Binding Protein (TARDBP), and Fused In Sarcoma (FUS); additional ALS-related genes including Charged Multivesicular Body Protein 2B (CHMP2B), Senataxin (SETX), Sequestosome 1 (SQSTM1), TANK Binding Kinase 1 (TBK1) and NIMA Related Kinase 1 (NEK1), have been identified. Mutations in these genes could impair different mechanisms, including vesicle transport, autophagy, and cytoskeletal or mitochondrial functions. So far, there is no effective therapy against ALS. Thus, early diagnosis and disease risk predictions remain one of the best options against ALS symptomologies. Proteomic biomarkers, microRNAs, and extracellular vehicles (EVs) serve as promising tools for disease diagnosis or progression assessment. These markers are relatively easy to obtain from blood or cerebrospinal fluids and can be used to identify potential genetic causative and risk factors even in the preclinical stage before symptoms appear. In addition, antisense oligonucleotides and RNA gene therapies have successfully been employed against other diseases, such as childhood-onset spinal muscular atrophy (SMA), which could also give hope to ALS patients. Therefore, an effective gene and biomarker panel should be generated for potentially "at risk" individuals to provide timely interventions and better treatment outcomes for ALS patients as soon as possible.}, } @article {pmid37565992, year = {2023}, author = {Cheng, JY and Deng, YT and Yu, JT}, title = {The causal role of circulating amino acids on neurodegenerative disorders: A two-sample Mendelian randomization study.}, journal = {Journal of neurochemistry}, volume = {166}, number = {6}, pages = {972-981}, doi = {10.1111/jnc.15937}, pmid = {37565992}, issn = {1471-4159}, mesh = {Humans ; Amino Acids/genetics ; Genome-Wide Association Study ; Mendelian Randomization Analysis ; *Neurodegenerative Diseases/genetics ; Glutamine ; *Parkinson Disease ; *Alzheimer Disease ; *Lewy Body Disease ; Causality ; }, abstract = {Potential associations between the risk of neurodegenerative diseases and circulating levels of amino acids have been implied in both experimental research and observational studies. However, because of the confounding and reverse causality, the findings could be biased. We aimed to determine whether circulating amino acid levels have potential effects on the risk of neurodegenerative diseases through a more robust analysis. So, we performed a total of two MR analyses, a discovery two-sample MR analysis, and a replication test, using summary-level genome-wide association study (GWAS) data, both with circulating levels of amino acids as exposure and risk of neurodegenerative diseases as an outcome. The potential causalities between nine amino acids (Glutamine [Glu], Leucine [Leu], Isoleucine [Ile], Phenylalanine [Phe], Valine [Val], Alanine [Ala], Tyrosine [Tyr], Histidine [His], and Glycine [Gly]) and six neurodegenerative disorders (Alzheimer's disease [AD], Parkinson's disease [PD], Multiple sclerosis [MS], Frontotemporal dementia [FTD], Lewy body dementia [DLB], Amyotrophic lateral sclerosis [ALS]) were explored in this study. According to the discovery MR analysis, 1 SD. increase in circulating levels of Gln was genetically determined to result in a 13% lower risk of AD (IVW ORSD [95% CI] = 0.872 [0.822, 0.926]; FDR = 7.46 × 10[-5]) while PD risk was decreased to 63% per SD. increase of circulating Leu levels (IVW ORSD [95% CI] = 0.628 [0.467, 0.843]; FDR = 0.021). Results from the replication test provide further evidence of the potential association between circulating Gln levels and AD risk (IVW ORSD [95% CI] = 0.094 [0.028, 0.311]; FDR = 9.98 × 10[-4]). Meanwhile, sensitivity analysis demonstrated that the significant relationships revealed by our two-sample MR outcomes were reliable. Our analyses provided robust evidence of causal associations between circulating levels of Gln and AD risk as well as circulating Leu levels and risk of PD. However, the underlying mechanisms remain to be further investigated.}, } @article {pmid37565261, year = {2023}, author = {Murphy, S and Schmitt-John, T and Dowling, P and Henry, M and Meleady, P and Swandulla, D and Ohlendieck, K}, title = {Proteomic profiling of the brain from the wobbler mouse model of amyotrophic lateral sclerosis reveals elevated levels of the astrogliosis marker glial fibrillary acidic protein.}, journal = {European journal of translational myology}, volume = {33}, number = {3}, pages = {}, pmid = {37565261}, issn = {2037-7452}, abstract = {The wobbler mouse is a widely used model system of amyotrophic lateral sclerosis and exhibits progressive neurodegeneration and neuroinflammation in association with skeletal muscle wasting. This study has used wobbler brain preparations for the systematic and mass spectrometric determination of proteome-wide changes. The proteomic characterization of total protein extracts from wobbler specimens was carried out with the help of an Orbitrap mass spectrometer and revealed elevated levels of glia cell marker proteins, i.e., glial fibrillary acidic protein and the actin-binding protein coronin. In contrast, the abundance of the actin-binding protein neurabin and the scaffolding protein named piccolo of the presynaptic cytomatrix were shown to be reduced. The increased abundance of glial fibrillary acidic protein, which is frequently used in neuropathological studies as a marker protein of glial scar formation, was confirmed by immunoblotting. In analogy, the proteomic profiling of the brain from another established murine model of motor neuron disease, the SOD1mouse, also showed increased levels of this intermediate filament protein. This suggests that neurodegenerative processes are associated with astrogliosis in both the wobbler and SOD1 brain.}, } @article {pmid37565183, year = {2023}, author = {Sheers, NL and O'Sullivan, R and Howard, ME and Berlowitz, DJ}, title = {The role of lung volume recruitment therapy in neuromuscular disease: a narrative review.}, journal = {Frontiers in rehabilitation sciences}, volume = {4}, number = {}, pages = {1164628}, pmid = {37565183}, issn = {2673-6861}, abstract = {Respiratory muscle weakness results in substantial discomfort, disability, and ultimately death in many neuromuscular diseases. Respiratory system impairment manifests as shallow breathing, poor cough and associated difficulty clearing mucus, respiratory tract infections, hypoventilation, sleep-disordered breathing, and chronic ventilatory failure. Ventilatory support (i.e., non-invasive ventilation) is an established and key treatment for the latter. As survival outcomes improve for people living with many neuromuscular diseases, there is a shift towards more proactive and preventative chronic disease multidisciplinary care models that aim to manage symptoms, improve morbidity, and reduce mortality. Clinical care guidelines typically recommend therapies to improve cough effectiveness and mobilise mucus, with the aim of averting acute respiratory compromise or respiratory tract infections. Moreover, preventing recurrent infective episodes may prevent secondary parenchymal pathology and further lung function decline. Regular use of techniques that augment lung volume has similarly been recommended (volume recruitment). It has been speculated that enhancing lung inflation in people with respiratory muscle weakness when well may improve respiratory system "flexibility", mitigate restrictive chest wall disease, and slow lung volume decline. Unfortunately, clinical care guidelines are based largely on clinical rationale and consensus opinion rather than level A evidence. This narrative review outlines the physiological changes that occur in people with neuromuscular disease and how these changes impact on breathing, cough, and respiratory tract infections. The biological rationale for lung volume recruitment is provided, and the clinical trials that examine the immediate, short-term, and longer-term outcomes of lung volume recruitment in paediatric and adult neuromuscular diseases are presented and the results synthesised.}, } @article {pmid37564731, year = {2023}, author = {Kudritzki, V and Howard, IM}, title = {Telehealth-based exercise in amyotrophic lateral sclerosis.}, journal = {Frontiers in neurology}, volume = {14}, number = {}, pages = {1238916}, pmid = {37564731}, issn = {1664-2295}, abstract = {The Veterans Health Administration (VHA) has served as a leader in the implementation of telerehabilitation technologies and continues to expand utilization of non-traditional patient encounters to better serve a geographically and demographically diverse population. Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disease impacting Veterans at a higher rate than the civilian population and associated with high levels of disability and limited access to subspecialized care. There is growing evidence supporting exercise-based interventions as an independent or adjunctive treatment to maintain or restore function for this patient population; many of these interventions can be delivered remotely by telehealth. The recent advancements in disease-modifying therapies for neuromuscular disorders will likely increase the importance of rehabilitation interventions to maximize functional outcomes. Here, we review the evidence for specific exercise interventions in ALS and the evidence for telehealth-based exercise in neuromuscular disorders. We then use this existing literature to propose a framework for telehealth delivery of these treatments, including feasible exercise interventions and remote outcome measures, recommended peripheral devices, and an example of a current remote group exercise program offered through VHA.}, } @article {pmid37564648, year = {2023}, author = {Calafatti, M and Cocozza, G and Limatola, C and Garofalo, S}, title = {Microglial crosstalk with astrocytes and immune cells in amyotrophic lateral sclerosis.}, journal = {Frontiers in immunology}, volume = {14}, number = {}, pages = {1223096}, pmid = {37564648}, issn = {1664-3224}, mesh = {Mice ; Animals ; Humans ; *Amyotrophic Lateral Sclerosis/genetics ; Microglia/pathology ; Astrocytes/pathology ; Motor Neurons/pathology ; }, abstract = {In recent years, biomedical research efforts aimed to unravel the mechanisms involved in motor neuron death that occurs in amyotrophic lateral sclerosis (ALS). While the main causes of disease progression were first sought in the motor neurons, more recent studies highlight the gliocentric theory demonstrating the pivotal role of microglia and astrocyte, but also of infiltrating immune cells, in the pathological processes that take place in the central nervous system microenvironment. From this point of view, microglia-astrocytes-lymphocytes crosstalk is fundamental to shape the microenvironment toward a pro-inflammatory one, enhancing neuronal damage. In this review, we dissect the current state-of-the-art knowledge of the microglial dialogue with other cell populations as one of the principal hallmarks of ALS progression. Particularly, we deeply investigate the microglia crosstalk with astrocytes and immune cells reporting in vitro and in vivo studies related to ALS mouse models and human patients. At last, we highlight the current experimental therapeutic approaches that aim to modulate microglial phenotype to revert the microenvironment, thus counteracting ALS progression.}, } @article {pmid37563264, year = {2023}, author = {Nag, S and Schneider, JA}, title = {Limbic-predominant age-related TDP43 encephalopathy (LATE) neuropathological change in neurodegenerative diseases.}, journal = {Nature reviews. Neurology}, volume = {19}, number = {9}, pages = {525-541}, pmid = {37563264}, issn = {1759-4766}, support = {P30 AG072975/AG/NIA NIH HHS/United States ; R01 AG042210/AG/NIA NIH HHS/United States ; R01 AG067482/AG/NIA NIH HHS/United States ; R01 AG017917/AG/NIA NIH HHS/United States ; P30 AG010161/AG/NIA NIH HHS/United States ; RF1 AG022018/AG/NIA NIH HHS/United States ; }, mesh = {*Frontotemporal Lobar Degeneration/diagnosis ; *Alzheimer Disease/pathology ; *Neurodegenerative Diseases ; Dementia ; TDP-43 Proteinopathies ; Humans ; *Amyotrophic Lateral Sclerosis/complications ; Adult ; *Frontotemporal Dementia/pathology ; Aged, 80 and over ; DNA-Binding Proteins ; }, abstract = {TAR DNA-binding protein 43 (TDP43) is a focus of research in late-onset dementias. TDP43 pathology in the brain was initially identified in amyotrophic lateral sclerosis and frontotemporal lobar degeneration, and later in Alzheimer disease (AD), other neurodegenerative diseases and ageing. Limbic-predominant age-related TDP43 encephalopathy (LATE), recognized as a clinical entity in 2019, is characterized by amnestic dementia resembling AD dementia and occurring most commonly in adults over 80 years of age. Neuropathological findings in LATE, referred to as LATE neuropathological change (LATE-NC), consist of neuronal and glial cytoplasmic TDP43 localized predominantly in limbic areas with or without coexisting hippocampal sclerosis and/or AD neuropathological change and without frontotemporal lobar degeneration or amyotrophic lateral sclerosis pathology. LATE-NC is frequently associated with one or more coexisting pathologies, mainly AD neuropathological change. The focus of this Review is the pathology, genetic risk factors and nature of the cognitive impairments and dementia in pure LATE-NC and in LATE-NC associated with coexisting pathologies. As the clinical and cognitive profile of LATE is currently not easily distinguishable from AD dementia, it is important to develop biomarkers to aid in the diagnosis of this condition in the clinic. The pathogenesis of LATE-NC should be a focus of future research to form the basis for the development of preventive and therapeutic strategies.}, } @article {pmid37562878, year = {2023}, author = {Weil, EL and Nakawah, MO and Masdeu, JC}, title = {Advances in the neuroimaging of motor disorders.}, journal = {Handbook of clinical neurology}, volume = {195}, number = {}, pages = {359-381}, doi = {10.1016/B978-0-323-98818-6.00039-X}, pmid = {37562878}, issn = {0072-9752}, mesh = {Humans ; Diffusion Tensor Imaging ; *Motor Disorders ; Neuroimaging/methods ; Magnetic Resonance Imaging/methods ; *Amyotrophic Lateral Sclerosis ; *Motor Neuron Disease/diagnostic imaging ; }, abstract = {Neuroimaging is a valuable adjunct to the history and examination in the evaluation of motor system disorders. Conventional imaging with computed tomography or magnetic resonance imaging depicts important anatomic information and helps to identify imaging patterns which may support diagnosis of a specific motor disorder. Advanced imaging techniques can provide further detail regarding volume, functional, or metabolic changes occurring in nervous system pathology. This chapter is an overview of the advances in neuroimaging with particular emphasis on both standard and less well-known advanced imaging techniques and findings, such as diffusion tensor imaging or volumetric studies, and their application to specific motor disorders. In addition, it provides reference to emerging imaging biomarkers in motor system disorders such as Parkinson disease, amyotrophic lateral sclerosis, and Huntington disease, and briefly reviews the neuroimaging findings in different causes of myelopathy and peripheral nerve disorders.}, } @article {pmid37562867, year = {2023}, author = {Mahjoub, Y and Martino, D}, title = {Immunology and microbiome: Implications for motor systems.}, journal = {Handbook of clinical neurology}, volume = {195}, number = {}, pages = {135-157}, doi = {10.1016/B978-0-323-98818-6.00001-7}, pmid = {37562867}, issn = {0072-9752}, mesh = {Animals ; Humans ; *Gastrointestinal Microbiome/physiology ; Dysbiosis ; *Tourette Syndrome ; *Microbiota ; *Parkinson Disease ; }, abstract = {Immune-inflammatory mechanisms seem to play a relevant role in neurodegenerative disorders affecting motor systems, particularly Parkinson's disease, where activity changes in inflammatory cells and evidence of neuroinflammation in experimental models and patients is available. Amyotrophic lateral sclerosis is also characterized by neuroinflammatory changes that involve primarily glial cells, both microglia and astrocytes, as well as systemic immune dysregulation associated with more rapid progression. Similarly, the exploration of gut dysbiosis in these two prototypical neurodegenerative motor disorders is advancing rapidly. Altered composition of gut microbial constituents and related metabolic and putative functional pathways is supporting a pathophysiological link that is currently explored in preclinical, germ-free animal models. Less compelling, but still intriguing, evidence suggests that motor neurodevelopmental disorders, e.g., Tourette syndrome, are associated with abnormal trajectories of maturation that include also immune system development. Microglia has a key role also in these disorders, and new therapeutic avenues aiming at its modulation are exciting prospects. Preclinical and clinical research on the role of gut dysbiosis in Tourette syndrome and related behavioral disorders is still in its infancy, but early findings support the rationale to delve deeper into its contribution to neural and immune maturation abnormalities in its spectrum.}, } @article {pmid37562449, year = {2023}, author = {Blackmer-Raynolds, L and Sampson, TR}, title = {Overview of the Gut Microbiome.}, journal = {Seminars in neurology}, volume = {43}, number = {4}, pages = {518-529}, doi = {10.1055/s-0043-1771463}, pmid = {37562449}, issn = {1098-9021}, mesh = {Animals ; Humans ; *Gastrointestinal Microbiome/physiology ; Quality of Life ; *Nervous System Diseases ; Brain ; *Parkinson Disease ; }, abstract = {The human gastrointestinal tract is home to trillions of microorganisms-collectively referred to as the gut microbiome-that maintain a symbiotic relationship with their host. This diverse community of microbes grows and changes as we do, with developmental, lifestyle, and environmental factors all shaping microbiome community structure. Increasing evidence suggests this relationship is bidirectional, with the microbiome also influencing host physiological processes. For example, changes in the gut microbiome have been shown to alter neurodevelopment and have lifelong effects on the brain and behavior. Age-related changes in gut microbiome composition have also been linked to inflammatory changes in the brain, perhaps increasing susceptibility to neurological disease. Indeed, associations between gut dysbiosis and many age-related neurological diseases-including Parkinson's disease, Alzheimer's disease, multiple sclerosis, and amyotrophic lateral sclerosis-have been reported. Further, microbiome manipulation in animal models of disease highlights a potential role for the gut microbiome in disease development and progression. Although much remains unknown, these associations open up an exciting new world of therapeutic targets, potentially allowing for improved quality of life for a wide range of patient populations.}, } @article {pmid37560029, year = {2023}, author = {Meng, J and Li, R and Huang, Q and Guo, D and Fan, K and Zhang, J and Zhu, X and Wang, M and Chen, X and Nie, D and Cao, C and Zhao, Z and Han, Z}, title = {Survey and toxigenic abilities of Aspergillus, Fusarium, and Alternaria fungi from wheat and paddy grains in Shanghai, China.}, journal = {Frontiers in plant science}, volume = {14}, number = {}, pages = {1202738}, pmid = {37560029}, issn = {1664-462X}, abstract = {A systematic study was carried out on 638 wheat and paddy grains (including fresh and stored samples) collected in 2021 from Shanghai, China, to identify the major mycobiota and their toxigenic abilities. A total of 349 fungi, namely, 252 Fusarium, 53 Aspergillus, and 44 Alternaria, were characterized by morphological and molecular identification. Fusarium and Aspergillus were more frequently isolated in paddy with Fusarium sambucinum species complex and Aspergillus section flavi as the predominant species, respectively. The genus Alternaria was the most frequently isolated fungal species in wheat. The toxin-producing potentials of the identified fungi were further evaluated in vitro. Deoxynevalenol (DON) was produced by 34.5% of Fusarium isolates and zearalenone (ZEN) was produced by 47.6% of them, and one isolate also processed the abilities for fumonisin B1 (FB1), B2 (FB2), and B3 (FB3) productions. Aflatoxin B1 (AFB1), B2 (AFB2), and G1 (AFG1) were only generated by Aspergillus section flavi, with the production rate of 65.5%, 27.6%, and 13.8%, respectively. Alternariol (AOH) was the most prevalent Alternaria toxin, which could be produced by 95.5% of the isolates, followed by alternariol monomethyl ether (AME) (72.7%), altenuene (ALT) (52.3%), tenuazonic acid (TeA) (45.5%), tentoxin (TEN) (29.5%), and altenusin (ALS) (4.5%). A combinational analysis of mycobiota and toxigenic ability allowed us to provide comprehensive information about the production mechanisms of mycotoxins in wheat and paddy in a specific geographic area, and will be helpful for developing efficient prevention and control programs.}, } @article {pmid37559423, year = {2023}, author = {Kim, S and An, S and Lee, J and Jeong, Y and You, CL and Kim, H and Bae, JH and Yun, CE and Ryu, D and Bae, GU and Kang, JS}, title = {Cdon ablation in motor neurons causes age-related motor neuron degeneration and impaired sciatic nerve repair.}, journal = {Journal of cachexia, sarcopenia and muscle}, volume = {14}, number = {5}, pages = {2239-2252}, pmid = {37559423}, issn = {2190-6009}, support = {NRF-2016R1A5A2945889//National Research Foundation Grant funded by the Korean Government (MSIP)/ ; NRF-2022R1A2B5B02001482//National Research Foundation Grant funded by the Korean Government (MSIP)/ ; }, abstract = {BACKGROUND: The functional deterioration and loss of motor neurons are tightly associated with degenerative motor neuron diseases and aging-related muscle wasting. Motor neuron diseases or aging-related muscle wasting in turn contribute to increased risk of adverse health outcomes in the elderly. Cdon (cell adhesion molecule-downregulated oncogene) belongs to the immunoglobulin superfamily of cell adhesion molecule and plays essential roles in multiple signalling pathways, including sonic hedgehog (Shh), netrin, and cadherin-mediated signalling. Cdon as a Shh coreceptor plays a critical role in motor neuron specification during embryonic development. However, its role in adult motor neuron function is unknown.

METHODS: Hb9-Cre recombinase-driven motor neuron-specific Cdon deficient mice (mnKO) and a compound mutant mice (mnKO::SOD1[G93A]) were generated to investigate the role of Cdon in motor neuron degeneration. Motor neuron regeneration was examined by using a sciatic nerve crush injury model. To investigate the phenotype, physical activity, compound muscle action potential, immunostaining, and transmission electron microscopy were carried out. In the mechanism study, RNA sequencing and RNA/protein analyses were employed.

RESULTS: Mice lacking Cdon in motor neurons exhibited middle age onset lethality and aging-related decline in motor function. In the sciatic nerve crush injury model, mnKO mice exhibited an impairment in motor function recovery evident by prolonged compound muscle action potential duration (4.63 ± 0.35 vs. 3.93 ± 0.22 s for f/f, P < 0.01) and physical activity. Consistently, neuromuscular junctions of mnKO muscles were incompletely occupied (49.79 ± 5.74 vs. 79.39 ± 3.77% fully occupied neuromuscular junctions for f/f, P < 0.0001), suggesting an impaired reinnervation. The transmission electron microscopy analysis revealed that mnKO sciatic nerves had smaller axon diameter (0.88 ± 0.13 vs. 1.43 ± 0.48 μm for f/f, P < 0.0001) and myelination defects. RNA sequencing of mnKO lumbar spinal cords showed alteration in genes related to neurogenesis, inflammation and cell death. Among the altered genes, ErbB4 and FgfR expressions were significantly altered in mnKO as well as in Cdon-depleted NSC34 motor neuron cells. Consistently, Cdon-depleted NSC34 cells exhibited elevated levels of cleaved Caspase3 and γH2AX proteins, as well as Bax transcription. Cdon-depleted NSC34 cells also exhibited impaired activation of Akt in response to neuregulin-1 (NRG1) treatment.

CONCLUSIONS: Our current data demonstrate the functional importance of Cdon in motor neuron function and nerve repair. Cdon ablation causes alterations in neurotrophin signalling that leads to motor neuron degeneration.}, } @article {pmid37558576, year = {2023}, author = {Prado, MB and Pedro, KM and Adiao, KJB}, title = {Efficacy, safety and tolerability of high caloric diet in amyotrophic lateral sclerosis patients: A systematic review and meta-analysis.}, journal = {Revue neurologique}, volume = {179}, number = {9}, pages = {1008-1019}, doi = {10.1016/j.neurol.2023.01.731}, pmid = {37558576}, issn = {0035-3787}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy ; Prospective Studies ; *Motor Neuron Disease ; Diet ; Carbohydrates/therapeutic use ; }, abstract = {BACKGROUND: Several randomized clinical trials were done to determine whether supplementation with a high caloric diet, either through carbohydrate or lipid supplementation, is safe, tolerable and improves survival. However, most of these trials are small and the results are conflicting.

METHODS: Randomized prospective trials utilizing high caloric supplementation among patients with amyotrophic lateral sclerosis (ALS) were searched using the terms [("amyotrophic lateral sclerosis" or "motor neuron disease" or "ALS" or "MND") and ("high calorie" or "high fat" or "high protein" or "high carbohydrate" or "supplementation")] in Medline, Cochrane, Embase, Scopus, Prospero and Herdin by two independent neurologists. Journal articles deemed relevant were assessed for eligibility.

MAIN RESULTS: There were 57 articles obtained from databases, 49 of which were excluded. Four articles were further excluded since all of them had different interventions. Overall, there were 311 ALS patients included in the study, 176 of them were from the intervention group while 135 were used as controls. Overall, high caloric supplementation in ALS was deemed safe and tolerable, and also when adverse events, tolerability and mortality are combined using meta-analysis. Although in most publications the efficacy of giving high caloric supplementation has been generally beneficial, some of the outcome parameters are not statistically different from controls when studies are combined using meta-analysis.

CONCLUSIONS: Current evidence suggests that high calorie supplementation is generally safe and tolerable for patients with ALS. However, it has not been shown to be efficacious in improving weight and functional disability.}, } @article {pmid37558109, year = {2023}, author = {Dave, U and Khan, S and Gomes, J}, title = {Characterization of E121K mutation of D-amino acid oxidase - Insights into mechanisms leading to amyotrophic lateral sclerosis.}, journal = {Biochimica et biophysica acta. Proteins and proteomics}, volume = {1871}, number = {6}, pages = {140947}, doi = {10.1016/j.bbapap.2023.140947}, pmid = {37558109}, issn = {1878-1454}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics ; Mutation ; Amino Acids/genetics ; Oxidoreductases/genetics ; India ; }, abstract = {D-amino acid oxidase (DAO) maintains the intracellular d-serine level which modulates the activity of the N-methyl-d-aspartate receptor and its dysfunction has been linked to several neurodegenerative disorders. In targeted next-generation sequencing study by our group, E121K mutation in DAO was associated with amyotrophic lateral sclerosis (ALS) in patients from India. However, variations in molecular mechanisms caused by this mutation which leads to ALS have not been studied. Hence, we carried out comparative biophysical characterization and assay studies of the wildtype- and mutant E121K-DAO. We observed that the purified E121K-DAO was inactive and exhibited a lower affinity for the FAD cofactor and benzoate inhibitor. Structural studies revealed that the E121K mutant has higher beta-sheet content, melting temperature, and oligomeric states compared to the wildtype. Kinetic study of aggregation of the variants using thioflavin-T confirmed that the E121K-DAO was more prone to aggregation. Microscopic visualization showed that the aggregation proceeds through an intermediate step involving the formation of fibrillar structures in the E121K mutant. Our results give insights into the underlying mechanisms leading to ALS pathogenesis.}, } @article {pmid37558082, year = {2024}, author = {Giannini, M and Porrua, O}, title = {Senataxin: A key actor in RNA metabolism, genome integrity and neurodegeneration.}, journal = {Biochimie}, volume = {217}, number = {}, pages = {10-19}, doi = {10.1016/j.biochi.2023.08.001}, pmid = {37558082}, issn = {1638-6183}, mesh = {Humans ; RNA Helicases/genetics/metabolism ; DNA Helicases/genetics/metabolism ; *Amyotrophic Lateral Sclerosis/genetics/metabolism ; *Neurodegenerative Diseases/genetics ; Transcription, Genetic ; Mutation ; Multifunctional Enzymes/genetics/metabolism ; RNA ; }, abstract = {The RNA/DNA helicase senataxin (SETX) has been involved in multiple crucial processes related to genome expression and integrity such us transcription termination, the regulation of transcription-replication conflicts and the resolution of R-loops. SETX has been the focus of numerous studies since the discovery that mutations in its coding gene are the root cause of two different neurodegenerative diseases: Ataxia with Oculomotor Apraxia type 2 (AOA2) and a juvenile form of Amyotrophic Lateral Sclerosis (ALS4). A plethora of cellular phenotypes have been described as the result of SETX deficiency, yet the precise molecular function of SETX as well as the molecular pathways leading from SETX mutations to AOA2 and ALS4 pathologies have remained unclear. However, recent data have shed light onto the biochemical activities and biological roles of SETX, thus providing new clues to understand the molecular consequences of SETX mutation. In this review we summarize near two decades of scientific effort to elucidate SETX function, we discuss strengths and limitations of the approaches and models used thus far to investigate SETX-associated diseases and suggest new possible research avenues for the study of AOA2 and ALS4 pathogenesis.}, } @article {pmid37558009, year = {2023}, author = {Monteiro Neto, JR and Ribeiro, GD and Magalhães, RSS and Follmer, C and Outeiro, TF and Eleutherio, ECA}, title = {Glycation modulates superoxide dismutase 1 aggregation and toxicity in models of sporadic amyotrophic lateral sclerosis.}, journal = {Biochimica et biophysica acta. Molecular basis of disease}, volume = {1869}, number = {8}, pages = {166835}, doi = {10.1016/j.bbadis.2023.166835}, pmid = {37558009}, issn = {1879-260X}, mesh = {Humans ; Superoxide Dismutase-1/genetics ; *Amyotrophic Lateral Sclerosis/pathology ; Superoxide Dismutase/metabolism ; Maillard Reaction ; Magnesium Oxide ; Motor Neurons/metabolism ; DNA-Binding Proteins/metabolism ; }, abstract = {Different SOD1 proteoforms are implicated## in both familial and sporadic cases of Amyotrophic Lateral Sclerosis (ALS), an aging-associated disease that affects motor neurons. SOD1 is crucial to neuronal metabolism and health, regulating the oxidative stress response and the shift between oxidative-fermentative metabolism, which is important for astrocyte-neuron metabolic cooperation. Neurons have a limited capacity to metabolize methylglyoxal (MGO), a potentially toxic side product of glycolysis. MGO is highly reactive and can readily posttranslationally modify proteins, in a reaction known as glycation, impacting their normal biology. Here, we aimed to investigate the effect of glycation on the aggregation and toxicity of human SOD1WT (hSOD1WT). Cells with deficiency in MGO metabolism showed increased levels of hSOD1WT inclusions, displaying also reduced hSOD1WT activity and viability. Strikingly, we also found that the presence of hSOD1WT in stress granules increased upon MGO treatment. The treatment of recombinant hSOD1WT with MGO resulted in the formation of SDS-stable oligomers, specially trimers, and thioflavin-T positive aggregates, which can promote cell toxicity and TDP-43 pathology. Together, our results suggest that glycation may play a still underappreciated role on hSOD1WT and TDP-43 pathologies in sporadic ALS, which could open novel perspectives for therapeutic intervention.}, } @article {pmid37556308, year = {2023}, author = {Kadambi, P and Stegmann, GM and Liss, J and Berisha, V and Hahn, S}, title = {Wav2DDK: Analytical and Clinical Validation of an Automated Diadochokinetic Rate Estimation Algorithm on Remotely Collected Speech.}, journal = {Journal of speech, language, and hearing research : JSLHR}, volume = {66}, number = {8S}, pages = {3166-3181}, pmid = {37556308}, issn = {1558-9102}, support = {R01 DC006859/DC/NIDCD NIH HHS/United States ; R21 DC019475/DC/NIDCD NIH HHS/United States ; }, mesh = {Humans ; *Speech ; *Amyotrophic Lateral Sclerosis ; Reproducibility of Results ; Speech Articulation Tests ; Algorithms ; }, abstract = {PURPOSE: Oral diadochokinesis is a useful task in assessment of speech motor function in the context of neurological disease. Remote collection of speech tasks provides a convenient alternative to in-clinic visits, but scoring these assessments can be a laborious process for clinicians. This work describes Wav2DDK, an automated algorithm for estimating the diadochokinetic (DDK) rate on remotely collected audio from healthy participants and participants with amyotrophic lateral sclerosis (ALS).

METHOD: Wav2DDK was developed using a corpus of 970 DDK assessments from healthy and ALS speakers where ground truth DDK rates were provided manually by trained annotators. The clinical utility of the algorithm was demonstrated on a corpus of 7,919 assessments collected longitudinally from 26 healthy controls and 82 ALS speakers. Corpora were collected via the participants' own mobile device, and instructions for speech elicitation were provided via a mobile app. DDK rate was estimated by parsing the character transcript from a deep neural network transformer acoustic model trained on healthy and ALS speech.

RESULTS: Algorithm estimated DDK rates are highly accurate, achieving .98 correlation with manual annotation, and an average error of only 0.071 syllables per second. The rate exactly matched ground truth for 83% of files and was within 0.5 syllables per second for 95% of files. Estimated rates achieve a high test-retest reliability (r = .95) and show good correlation with the revised ALS functional rating scale speech subscore (r = .67).

CONCLUSION: We demonstrate a system for automated DDK estimation that increases efficiency of calculation beyond manual annotation. Thorough analytical and clinical validation demonstrates that the algorithm is not only highly accurate, but also provides a convenient, clinically relevant metric for tracking longitudinal decline in ALS, serving to promote participation and diversity of participants in clinical research.

SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.23787033.}, } @article {pmid37556038, year = {2023}, author = {Yamamuro-Tanabe, A and Mukai, Y and Kojima, W and Zheng, S and Matsumoto, N and Takada, S and Mizuhara, M and Kosuge, Y and Ishimaru, Y and Yoshioka, Y}, title = {An Increase in Peroxiredoxin 6 Expression Induces Neurotoxic A1 Astrocytes in the Lumbar Spinal Cord of Amyotrophic Lateral Sclerosis Mice Model.}, journal = {Neurochemical research}, volume = {48}, number = {12}, pages = {3571-3584}, pmid = {37556038}, issn = {1573-6903}, mesh = {Mice ; Humans ; Animals ; *Amyotrophic Lateral Sclerosis/metabolism ; Astrocytes/metabolism ; Peroxiredoxin VI/genetics/metabolism ; *Neurodegenerative Diseases/metabolism ; Mice, Transgenic ; Spinal Cord/metabolism ; Cytokines/metabolism ; Disease Models, Animal ; *Neurotoxicity Syndromes/metabolism ; RNA, Messenger/metabolism ; Superoxide Dismutase-1/genetics ; Superoxide Dismutase/metabolism ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a severe neurodegenerative disease with selective degeneration of motor neurons. It has been reported that an increase in the levels of inflammatory cytokines and glial cells such as reactive astrocytes is closely involved in the pathological progression of ALS. Recently, the levels of neuropathic cytotoxic (A1) astrocytes among reactive astrocytes have reportedly increased in the central nervous system of ALS mice, which induce motor neuron degeneration through the production of inflammatory cytokines and secretion of neuropathic factors. Hence, elucidating the induction mechanism of A1 astrocytes in ALS is important to understand the mechanism of disease progression in ALS. In this study, we observed that the expression of peroxiredoxin 6 (PRDX6), a member of the peroxiredoxin family, was markedly upregulated in astrocytes of the lumbar spinal cord of SOD1[G93A] mice model for ALS. Additionally, when PRDX6 was transiently transfected into the mouse astrocyte cell line C8-D1A and human astrocytoma cell line U-251 MG, the mRNA expression of complement C3 (a marker for A1 astrocyte phenotype) and inflammatory cytokines was increased. Furthermore, the mRNA expression of C3 and inflammatory cytokine was increased in C8-D1A and U-251 MG cells stably expressing PRDX6, and the increased mRNA expression was significantly suppressed by MJ33 (lithium[1-hexadecoxy-3-(2,2,2-trifluoroethoxy) propan-2-yl] methyl phosphate), an inhibitor of the phospholipase A2 activity of PRDX6. Our results suggest that the expression of PRDX6 in astrocytes plays an important role in the induction of A1 astrocytes and expression of inflammatory cytokines in the ALS mice model.}, } @article {pmid37555859, year = {2023}, author = {Tsuboguchi, S and Nakamura, Y and Ishihara, T and Kato, T and Sato, T and Koyama, A and Mori, H and Koike, Y and Onodera, O and Ueno, M}, title = {TDP-43 differentially propagates to induce antero- and retrograde degeneration in the corticospinal circuits in mouse focal ALS models.}, journal = {Acta neuropathologica}, volume = {146}, number = {4}, pages = {611-629}, pmid = {37555859}, issn = {1432-0533}, mesh = {Animals ; Mice ; *Amyotrophic Lateral Sclerosis/pathology ; DNA-Binding Proteins/genetics/metabolism ; Motor Neurons/metabolism ; *Retrograde Degeneration/metabolism/pathology ; Spinal Cord/pathology ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by TDP-43 inclusions in the cortical and spinal motor neurons. It remains unknown whether and how pathogenic TDP-43 spreads across neural connections to progress degenerative processes in the cortico-spinal motor circuitry. Here we established novel mouse ALS models that initially induced mutant TDP-43 inclusions in specific neuronal or cell types in the motor circuits, and investigated whether TDP-43 and relevant pathological processes spread across neuronal or cellular connections. We first developed ALS models that primarily induced TDP-43 inclusions in the corticospinal neurons, spinal motor neurons, or forelimb skeletal muscle, by using adeno-associated virus (AAV) expressing mutant TDP-43. We found that TDP-43 induced in the corticospinal neurons was transported along the axons anterogradely and transferred to the oligodendrocytes along the corticospinal tract (CST), coinciding with mild axon degeneration. In contrast, TDP-43 introduced in the spinal motor neurons did not spread retrogradely to the cortical or spinal neurons; however, it induced an extreme loss of spinal motor neurons and subsequent degeneration of neighboring spinal neurons, suggesting a degenerative propagation in a retrograde manner in the spinal cord. The intraspinal degeneration further led to severe muscle atrophy. Finally, TDP-43 induced in the skeletal muscle did not propagate pathological events to spinal neurons retrogradely. Our data revealed that mutant TDP-43 spread across neuro-glial connections anterogradely in the corticospinal pathway, whereas it exhibited different retrograde degenerative properties in the spinal circuits. This suggests that pathogenic TDP-43 may induce distinct antero- and retrograde mechanisms of degeneration in the motor system in ALS.}, } @article {pmid37555725, year = {2024}, author = {Wei, F and Liang, X and Shi, JC and Luo, JN and Qiu, LJ and Li, XX and Lu, LJ and Wen, YQ and Feng, JY}, title = {Pan-Genomic Analysis Identifies the Chinese Strain as a New Subspecies of Xanthomonas fragariae.}, journal = {Plant disease}, volume = {108}, number = {1}, pages = {45-49}, doi = {10.1094/PDIS-05-23-0933-SC}, pmid = {37555725}, issn = {0191-2917}, mesh = {*Genomics ; Multilocus Sequence Typing ; *Xanthomonas/genetics ; }, abstract = {Xanthomonas fragariae is classified as a quarantine pathogen by the European and Mediterranean Plant Protection Organization. It commonly induces typical angular leaf spot (ALS) symptoms in strawberry leaves. X. fragariae strains from China (YL19, SHAQP01, and YLX21) exhibit ALS symptoms in leaves and more severe symptoms of dry cavity rot in strawberry crowns. Conversely, strains from other countries do not cause severe dry cavity rot symptoms in strawberries. After employing multilocus sequence analysis (MLSA), average nucleotide identity (ANI), and amino acid identity (AAI), we determined that Chinese strains of X. fragariae are genetically distinct from other strains and can be considered a new subspecies. Subsequent analysis of 63 X. fragariae genomes published at NCBI using IPGA and EDGAR3.0 revealed the pan-genomic profile, with 1,680 shared genes present in all 63 strains, including 71 virulence-related genes. Additionally, we identified 123 genes exclusive to all the Chinese strains, encompassing 12 virulence-related genes. The qRT-PCR analysis demonstrated that the expression of XopD, XopG1, CE8, GT2, and GH121 out of 12 virulence-related genes of Chinese strains (YL19) exhibited a constant increase in the early stages (6, 24, 54, and 96 hours postinoculation [hpi]) of strawberry leaf infected by YL19. So, the presence of XopD, XopG1, CE8, GT2, and GH121 in Chinese strains may play important roles in the early infection process of Chinese strains. These findings offer novel insights into comprehending the population structure and variation in the pathogenic capacity of X. fragariae.}, } @article {pmid37555646, year = {2023}, author = {Ribeiro, SS and Gnutt, D and Azoulay-Ginsburg, S and Fetahaj, Z and Spurlock, E and Lindner, F and Kuz, D and Cohen-Erez, Y and Rapaport, H and Israelson, A and Gruzman, AL and Ebbinghaus, S}, title = {Intracellular spatially-targeted chemical chaperones increase native state stability of mutant SOD1 barrel.}, journal = {Biological chemistry}, volume = {404}, number = {10}, pages = {909-930}, pmid = {37555646}, issn = {1437-4315}, mesh = {Humans ; Superoxide Dismutase-1/genetics/chemistry/metabolism ; *Amyotrophic Lateral Sclerosis/drug therapy ; Protein Folding ; Mutation ; Molecular Chaperones ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurological disorder with currently no cure. Central to the cellular dysfunction associated with this fatal proteinopathy is the accumulation of unfolded/misfolded superoxide dismutase 1 (SOD1) in various subcellular locations. The molecular mechanism driving the formation of SOD1 aggregates is not fully understood but numerous studies suggest that aberrant aggregation escalates with folding instability of mutant apoSOD1. Recent advances on combining organelle-targeting therapies with the anti-aggregation capacity of chemical chaperones have successfully reduce the subcellular load of misfolded/aggregated SOD1 as well as their downstream anomalous cellular processes at low concentrations (micromolar range). Nevertheless, if such local aggregate reduction directly correlates with increased folding stability remains to be explored. To fill this gap, we synthesized and tested here the effect of 9 ER-, mitochondria- and lysosome-targeted chemical chaperones on the folding stability of truncated monomeric SOD1 (SOD1bar) mutants directed to those organelles. We found that compound ER-15 specifically increased the native state stability of ER-SOD1bar-A4V, while scaffold compound FDA-approved 4-phenylbutyric acid (PBA) decreased it. Furthermore, our results suggested that ER15 mechanism of action is distinct from that of PBA, opening new therapeutic perspectives of this novel chemical chaperone on ALS treatment.}, } @article {pmid37555559, year = {2023}, author = {Reimer, RJ and Goncalves, A and Soper, B and Cadena, J and Wilson, JL and Gryshuk, AL and Suarez, P and Osborne, TF and Grimes, KV and Ray, P}, title = {An electronic health record cohort of Veterans with amyotrophic lateral sclerosis.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {}, number = {}, pages = {1-7}, doi = {10.1080/21678421.2023.2239300}, pmid = {37555559}, issn = {2167-9223}, abstract = {Objective: To assemble and characterize an electronic health record (EHR) dataset for a large cohort of US military Veterans diagnosed with ALS (Amyotrophic Lateral Sclerosis). Methods: An EHR dataset for 19,662 Veterans diagnosed with ALS between January 1, 2000 to December 31, 2020 was compiled from the Veterans Health Administration (VHA) EHR database by a query for ICD9 diagnosis (335.20) or ICD10 diagnosis (G12.21) for Amyotrophic Lateral Sclerosis. Results: The cohort is predominantly male (98.94%) and white (72.37%) with a median age at disease onset of 68 years and median survival from the date of diagnosis of 590 days. With the designation of ALS as a compensable illness in 2009, there was a subsequent increase in the number of Veterans diagnosed per year in the VHA, but no change in median survival. The cohort included a greater-than-expected proportion of individuals whose branch of service at the time of separation was the Army. Conclusions: The composition of the cohort reflects the VHA population who are at greatest risk for ALS. The greater than expected proportion of individuals whose branch of service at the time of separation was the Army suggests the possibility of a branch-specific risk factor for ALS.}, } @article {pmid37554051, year = {2023}, author = {Cao, W and Cao, Z and Tian, Y and Zhang, L and Wang, W and Tang, L and Xu, C and Fan, D}, title = {Neutrophils Are Associated with Higher Risk of Incident Amyotrophic Lateral Sclerosis in a BMI- and Age-Dependent Manner.}, journal = {Annals of neurology}, volume = {94}, number = {5}, pages = {942-954}, doi = {10.1002/ana.26760}, pmid = {37554051}, issn = {1531-8249}, mesh = {Humans ; Aged ; *Neutrophils ; *Amyotrophic Lateral Sclerosis/epidemiology ; Body Mass Index ; Lymphocytes ; Prognosis ; Biomarkers ; Retrospective Studies ; Inflammation ; }, abstract = {OBJECTIVE: Peripheral immune markers have been associated with the progression and prognosis of amyotrophic lateral sclerosis (ALS). However, whether dysregulation of peripheral immunity is a risk factor for ALS or a consequence of motor neuron degeneration has not yet been clarified. We aimed to identify longitudinal associations between prediagnostic peripheral immunity and the risk of incident ALS.

METHODS: A total of 345,000 individuals from the UK Biobank between 2006 and 2010 were included at the baseline. The counts of peripheral immune markers (neutrophils, lymphocytes, monocytes, platelets, and CRP) and its derived metrics (neutrophil-to-lymphocyte ratio [NLR], platelet-to-lymphocyte ratio [PLR], lymphocyte-to-monocyte ratio [LMR], and systemic immune-inflammation index [SII]) were analyzed in relation to the following incident ALS by Cox proportional hazard models. Subgroup and interaction analyses were performed to explore the covariates of these relationships further.

RESULTS: After adjusting for all covariates, the multivariate analysis showed that high neutrophil counts and their derived metrics (NLR and SII) were associated with an increased risk of ALS incidence (per SD increment hazard ratio [HR] = 1.15, 95% confidence interval [CI] = 1.02-1.29 for neutrophils; HR = 1.15, 95% CI = 1.03-1.28 for NLR; and HR = 1.17, 95% CI = 1.05-1.30 for SII). Subgroup and interaction analyses revealed that body mass index (BMI) and age had specific effects on this association. In participants with BMI ≥ 25 or age < 65 years, higher neutrophil counts, and their metrics increased the risk of incident ALS; however, in participants with BMI < 25 or age ≥ 65 years, neutrophils had no effect on incident ALS.

INTERPRETATION: Our study provides evidence that increased neutrophil levels and neutrophil-derived metrics (NLR and SII) are associated with an increased risk of developing ALS. ANN NEUROL 2023;94:942-954.}, } @article {pmid37552461, year = {2023}, author = {Weeks, RD and Banack, SA and Howell, S and Thunga, P and Metcalf, JS and Green, AJ and Cox, PA and Planchart, A}, title = {The Effects of Long-term, Low-dose β-N-methylamino-L-alanine (BMAA) Exposures in Adult SOD[G93R] Transgenic Zebrafish.}, journal = {Neurotoxicity research}, volume = {41}, number = {5}, pages = {481-495}, pmid = {37552461}, issn = {1476-3524}, support = {P30 ES025128/ES/NIEHS NIH HHS/United States ; T32 ES007046/ES/NIEHS NIH HHS/United States ; }, mesh = {Animals ; Zebrafish ; *Neurodegenerative Diseases/etiology ; *Amyotrophic Lateral Sclerosis/chemically induced/genetics/complications ; *Amino Acids, Diamino/toxicity ; Animals, Genetically Modified ; Neurotoxins/toxicity ; Superoxide Dismutase ; }, abstract = {β-N-Methylamino-L-alanine (BMAA) is a non-proteinogenic amino acid produced by cyanobacteria, which has been implicated in several neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). It is postulated that chronic exposure to BMAA can lead to formation of protein aggregates, oxidative stress, and/or excitotoxicity, which are mechanisms involved in the etiology of ALS. While specific genetic mutations are identified in some instances of ALS, it is likely that a combination of genetic and environmental factors, such as exposure to the neurotoxin BMAA, contributes to disease. We used a transgenic zebrafish with an ALS-associated mutation, compared with wild-type fish to explore the potential neurotoxic effects of BMAA through chronic long-term exposures. While our results revealed low concentrations of BMAA in the brains of exposed fish, we found no evidence of decreased swim performance or behavioral differences that might be reflective of neurodegenerative disease. Further research is needed to determine if chronic BMAA exposure in adult zebrafish is a suitable model to study neurodegenerative disease initiation and/or progression.}, } @article {pmid37550954, year = {2023}, author = {Weemering, DN and Midei, M and Milner, P and Gopalakrishnan, V and Kumar, A and Dannenberg, AJ and Bunte, TM and Foucher, J and Ingre, C and Ķēniņa, V and Rallmann, K and van den Berg, LH and van Eijk, RPA}, title = {A randomized, double-blind, placebo-controlled phase 2 study to assess safety, tolerability, and efficacy of RT001 in patients with amyotrophic lateral sclerosis.}, journal = {European journal of neurology}, volume = {30}, number = {12}, pages = {3722-3731}, doi = {10.1111/ene.16020}, pmid = {37550954}, issn = {1468-1331}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis ; Linoleic Acids/therapeutic use ; Double-Blind Method ; Treatment Outcome ; }, abstract = {BACKGROUND AND PURPOSE: RT001 is a deuterated synthetic homologue of linoleic acid, which makes membrane polyunsaturated fatty acids resistant to lipid peroxidation, a process involved in motor neuron degeneration in amyotrophic lateral sclerosis (ALS).

METHODS: We conducted a randomized, multicenter, placebo-controlled clinical trial. Patients with ALS were randomly allocated to receive either RT001 or placebo for 24 weeks. After the double-blind period, all patients received RT001 during an open-label phase for 24 weeks. The primary outcome measures were safety and tolerability. Key efficacy outcomes included the ALS Functional Rating Scale (ALSFRS-R), percent predicted slow vital capacity, and plasma neurofilament light chain concentration.

RESULTS: In total, 43 patients (RT001 = 21; placebo = 22) were randomized. RT001 was well tolerated; one patient required dose reduction due to adverse events (AEs). Numerically, there were more AEs in the RT001 group compared to the placebo group (71% versus 55%, p = 0.35), with gastrointestinal symptoms being the most common (43% in RT001, 27% in placebo, p = 0.35). Two patients in the RT001 group experienced a serious AE, though unrelated to treatment. The least-squares mean difference in ALSFRS-R total score at week 24 of treatment was 1.90 (95% confidence interval = -1.39 to 5.19) in favor of RT001 (p = 0.25). The directions of other efficacy outcomes favored RT001 compared to placebo, although no inferential statistics were performed.

CONCLUSIONS: Initial data indicate that RT001 is safe and well tolerated. Given the exploratory nature of the study, a larger clinical trial is required to evaluate its efficacy.}, } @article {pmid37550578, year = {2024}, author = {Maksymowicz, S and Siwek, T}, title = {Diagnostic odyssey in amyotrophic lateral sclerosis: diagnostic criteria and reality.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {45}, number = {1}, pages = {191-196}, pmid = {37550578}, issn = {1590-3478}, mesh = {Male ; Female ; Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/therapy ; Quality of Life ; *Physicians ; Rare Diseases ; }, abstract = {BACKGROUND: Diagnosing a rare disease, such as amyotrophic lateral sclerosis, is a major challenge for physicians and patients. Despite detailed diagnostic criteria, this process often does not proceed as it should, exacerbating the problems of patients. In the following study, we show how the process, which in medical sciences has been called the "diagnostic odyssey", proceeds and how it affects patients.

MATERIALS AND METHODS: Participants were recruited via a neurology clinic. Twenty-four patients with the diagnosed disease were interviewed using in-depth interviews and an author questionnaire: 9 females and 15 males ages ranging from 30-39 to 60-69.

RESULTS: The median time from 1st symptoms to diagnosis was almost 12 months and mean almost 20 months (min. 3, max 106). Only 5 patients waited less than 6 months for being diagnosed. Over 80% of patients received an alternative diagnosis on the first attempt.

CONCLUSION: ALS is a fast-paced fatal disease, which requires immediate action to slow down the course of the disease and improve patients' quality of life. However, in many cases, the disease is diagnosed too late. It also happens that a wrong diagnosis causes inaccurate treatment, which accelerates the development of ALS. For this reason, it is necessary to expand the clinical and communication competences of medical personnel already at the stage of medical studies. In addition, the diagnostic criteria should highlight the common problem with diagnosing ALS.}, } @article {pmid37550499, year = {2023}, author = {Wang, XH and Peng, BB and Zhang, L and Zhao, J and Zhang, L and Ren, H and Hu, P and Li, H and Zhong, S}, title = {Mixed mode of artificial liver support in patients with acute-on-chronic liver failure: a retrospective cohort study.}, journal = {Hepatology international}, volume = {17}, number = {5}, pages = {1241-1250}, pmid = {37550499}, issn = {1936-0541}, support = {82173237//National Natural Science Foundation of China/ ; 81902068//National Natural Science Foundation of China/ ; No. [2022]15//Senior Medical Talents Program of Chongqing for Young and Middle-aged/ ; W0082//Program for Youth Innovation in Future Medicine, Chongqing Medical University/ ; Shan Zhong//Kuanren Talents Program of the Second Affiliated Hospital of Chongqing Medical University/ ; Hu Li//Kuanren Talents Program of the Second Affiliated Hospital of Chongqing Medical University/ ; }, mesh = {Female ; Humans ; Male ; *Acute-On-Chronic Liver Failure/mortality ; Liver Cirrhosis/complications ; *Liver, Artificial/adverse effects ; Prognosis ; Retrospective Studies ; }, abstract = {BACKGROUND AND AIMS: Different modes of artificial liver support (ALS) therapy can improve the survival of patients with acute-on-chronic liver failure (ACLF). This study aimed to compare the effects of mixed using different modes of ALS (MALS) and single using one mode of ALS (SALS) on 28- and 90-day survival rates of ACLF.

METHODS: Clinical data and survival times of patients with ACLF treated for ALS between January 1, 2018 and December 30, 2021 were retrospectively collected. Cox regression analysis was performed to identify risk factors of 28- and 90-day mortalities.

RESULTS: Of the 462 eligible ACLF patients, 388 belonged to the SALS group (76.3% male, 74.2% cirrhosis) and 74 to the MALS group (86.5% male, 71.6% cirrhosis). Comparison of 28-day and 90-day crude mortality between the SALS and MALS groups showed no significant differences (28-day: 20.4% vs. 14.9%, p = 0.27; 90-day: 44.6% vs. 52.7%, p = 0.20). After adjusting for confounders, the 28-day mortality (adjusted hazard ratio [aHR]: 0.32, 95% confidence interval [CI] 0.16-0.65) and 90-day mortality (aHR: 0.65, 95% CI 0.44-0.95) in the MALS group were significantly lower than those in the SALS group. These associations were consistently observed across pre-specified subgroups according to age, sex, etiology, and Child-Pugh grade. However, positive interactions between MALS and 90-day mortality were found between MALS and 90-day mortality in those with MELD score ≥ 22 and international normalized ratio ≥ 1.9 (p for interaction < 0.05).

CONCLUSION: MALS therapy significantly decreased 28- and 90-day mortalities of ACLF than SALS did, especially in advanced stages.}, } @article {pmid37549725, year = {2023}, author = {Fan, H and Bai, Q and Yang, Y and Shi, X and Du, G and Yan, J and Shi, J and Wang, D}, title = {The key roles of reactive oxygen species in microglial inflammatory activation: Regulation by endogenous antioxidant system and exogenous sulfur-containing compounds.}, journal = {European journal of pharmacology}, volume = {956}, number = {}, pages = {175966}, doi = {10.1016/j.ejphar.2023.175966}, pmid = {37549725}, issn = {1879-0712}, mesh = {Humans ; *Antioxidants/pharmacology/metabolism ; Reactive Oxygen Species/metabolism ; *Microglia ; Sulfur Compounds/metabolism/pharmacology ; Neuroinflammatory Diseases ; Cysteine/pharmacology ; Sulfur/metabolism/pharmacology ; }, abstract = {Aberrant innate immunity in the brain has been implicated in the pathogenesis of several central nervous system (CNS) disorders, including Alzheimer's disease, Huntington's disease, Parkinson's disease, stroke, amyotrophic lateral sclerosis, and depression. Except for extraparenchymal CNS-associated macrophages, which predominantly afford protection against peripheral invading pathogens, it has been reported that microglia, a population of macrophage-like cells governing CNS immune defense in nearly all neurological diseases, are the main CNS resident immune cells. Although microglia have been recognized as the most important source of reactive oxygen species (ROS) in the CNS, ROS also may underlie microglial functions, especially M1 polarization, by modulating redox-sensitive signaling pathways. Recently, endogenous antioxidant systems, including glutathione, hydrogen sulfide, superoxide dismutase, and methionine sulfoxide reductase A, were found to be involved in regulating microglia-mediated neuroinflammation. A series of natural sulfur-containing compounds, including S-adenosyl methionine, S-methyl-L-cysteine, sulforaphane, DMS, and S-alk(enyl)-l-cysteine sulfoxide, modulating endogenous antioxidant systems have been discovered. We have summarized the current knowledge on the involvement of endogenous antioxidant systems in regulating microglial inflammatory activation and the effects of sulfur-containing compounds on endogenous antioxidant systems. Finally, we discuss the possibilities associated with compounds targeting the endogenous antioxidant system to treat neuroinflammation-associated diseases.}, } @article {pmid37548757, year = {2024}, author = {Zhu, Y and Huo, Y and Bai, J and Li, M and Wang, H and Wang, J and Huang, X}, title = {Serum Cystatin C is a potential biomarker for predicting amyotrophic lateral sclerosis survival.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {45}, number = {1}, pages = {197-201}, pmid = {37548757}, issn = {1590-3478}, mesh = {Female ; Humans ; Male ; *Amyotrophic Lateral Sclerosis ; Biomarkers ; Cystatin C ; Delayed Diagnosis ; Disease Progression ; Prognosis ; }, abstract = {OBJECTIVE: Currently, it is unclear whether serum Cystatin C can be used to evaluate the prognosis of ALS. We aim to study the relationship between serum Cystatin C and survival in ALS.

METHODS: Sporadic ALS patients diagnosed at the Department of Neurology, the First Medical Center, and the Chinese PLA General Hospital from January 2016 to December 2019 were enrolled in this study. Experienced neurologists followed up the participants regularly every 6 months until January 2022. According to the levels of serum Cystatin C, the participants were divided into high and low Cystatin C levels groups. The comparison between groups was performed with parametric or non-parametric test. Kaplan-Meier method and Cox regression model were used to calculate survival analysis.

RESULTS: Three hundred fifty-six sporadic ALS patients were enrolled in this study, including 203 males and 153 females. Among all ALS patients, 26 cases (7.3%) were lost to follow-up, 226 cases (63.5%) died, and 104 cases (29.2%) were still alive at the last follow-up. The median survival time of all ALS patients was 42.0 months. Patients with high Cystatin C levels had shorter median survival than those with lower Cystatin C levels (38.0 months vs. 48.0 months, P = 2.58 × 10[-4]). In multivariate Cox regression analysis, onset form, age of onset, diagnostic delay, disease progression rate, creatinine, and serum Cystatin C levels were associated with ALS survival.

CONCLUSIONS: Our study found that serum Cystatin C was associated with ALS survival, and serum Cystatin C level might be an independent predictor of ALS survival.}, } @article {pmid37548234, year = {2023}, author = {Notarstefano, V and Belloni, A and Mariani, P and Orilisi, G and Orsini, G and Giorgini, E and Byrne, HJ}, title = {Multivariate curve Resolution-Alternating least squares coupled with Raman microspectroscopy: new insights into the kinetic response of primary oral squamous carcinoma cells to cisplatin.}, journal = {The Analyst}, volume = {148}, number = {18}, pages = {4365-4372}, doi = {10.1039/d3an01182h}, pmid = {37548234}, issn = {1364-5528}, mesh = {Humans ; *Cisplatin/pharmacology ; Least-Squares Analysis ; Spectrum Analysis, Raman/methods ; *Carcinoma, Squamous Cell/drug therapy ; Multivariate Analysis ; }, abstract = {Raman MicroSpectroscopy (RMS) is a powerful label-free tool to probe the effects of drugs at a cellular/subcellular level. It is important, however, to be able to extract relevant biochemical and kinetic spectroscopic signatures of the specific cellular responses. In the present study, a combination of Multivariate Curve Resolution-Alternating Least Squares (MCR-ALS) and Principal Component Analysis (PCA) is used to analyse the RMS data for the example of exposure of primary Oral Squamous Carcinoma Cells (OSCC) to the chemotherapeutic agent cisplatin. Dosing regimens were established by cytotoxicity assays, and the effects of the drug on cellular spectral profiles were monitored from 16 to 72 hours post-exposure using an apoptosis assay, to establish the relative populations of viable (V), early (EA) and late apoptotic/dead (LA/D) cells after the drug treatment. Based on a kinetic model of the progression from V > EA > D, MCR-ALS regression analysis of the RMS responses was able to extract spectral profiles associated with each stage of the cellular responses, enabling a quantitative comparison of the response rates for the respective drug treatments. Moreover, PCA was used to compare the spectral profiles of the viable cells exposed to the drug. Spectral differences were highlighted in the early stages (16 hours exposure), indicative of the initial cellular response to the drug treatment, and also in the late stages (48-72 hours exposure), representing the cell death pathway. The study demonstrates that RMS coupled with multivariate analysis can be used to quantitatively monitor the progression of cellular responses to different drugs, towards future applications for label-free, in vitro, pre-clinical screening.}, } @article {pmid37548032, year = {2024}, author = {LeBlanc, MA and Gough, A and Rideout, AL and Dyack, S and Singh, K and MacNeil, M}, title = {Atypical Neuropsychiatric Presentation of FTD-ALS Caused by a Pathogenic Repeat Expansion in C9orf72: A Case Report.}, journal = {Journal of geriatric psychiatry and neurology}, volume = {37}, number = {2}, pages = {157-162}, pmid = {37548032}, issn = {1552-5708}, mesh = {Humans ; Male ; *Amyotrophic Lateral Sclerosis/diagnosis/genetics ; C9orf72 Protein/genetics ; DNA Repeat Expansion ; *Frontotemporal Dementia/diagnosis/genetics ; Mutation ; Adult ; }, abstract = {The case report describes the presentation of a 42-year-old male ultimately diagnosed with FTD-ALS caused by a genetic mutation, who initially presented with atypical psychiatric symptoms. Given that the initial clinical manifestations of FTD-ALS can be quite variable, the diagnosis is often challenging; the case report aims to highlight several key considerations in the diagnostic assessment, including genetic testing in order to guide clinicians in more timely diagnosis and ultimately improve patient care.}, } @article {pmid37547740, year = {2023}, author = {Aiello, EN and Solca, F and Torre, S and Patisso, V and De Lorenzo, A and Treddenti, M and Colombo, E and Maranzano, A and Morelli, C and Doretti, A and Verde, F and Silani, V and Ticozzi, N and Poletti, B}, title = {Bulbar involvement and cognitive features in amyotrophic lateral sclerosis: a retrospective study on 347 patients.}, journal = {Frontiers in aging neuroscience}, volume = {15}, number = {}, pages = {1217080}, pmid = {37547740}, issn = {1663-4365}, abstract = {BACKGROUND: This study aimed at clarifying the role of bulbar involvement (BI) as a risk factor for cognitive impairment (CI) in non-demented amyotrophic lateral sclerosis (ALS) patients.

METHODS: Data on N = 347 patients were retrospectively collected. Cognition was assessed via the Edinburgh Cognitive and Behavioral ALS Screen (ECAS). On the basis of clinical records and ALS Functional Rating Scale-Revised (ALSFRS-R) scores, BI was characterized as follows: (1) BI at onset-from medical history; (2) BI at testing (an ALSFRS-R-Bulbar score ≤11); (3) dysarthria (a score ≤3 on item 1 of the ALSFRS-R); (4) severity of BI (the total score on the ALSFRS-R-Bulbar); and (5) progression rate of BI (computed as 12-ALSFRS-R-Bulbar/disease duration in months). Logistic regressions were run to predict a below- vs. above-cutoff performance on each ECAS measure based on BI-related features while accounting for sex, disease duration, severity and progression rate of respiratory and spinal involvement and ECAS response modality.

RESULTS: No predictors yielded significance either on the ECAS-Total and -ALS-non-specific or on ECAS-Language/-Fluency or -Visuospatial subscales. BI at testing predicted a higher probability of an abnormal performance on the ECAS-ALS-specific (p = 0.035) and ECAS-Executive Functioning (p = 0.018). Lower ALSFRS-R-Bulbar scores were associated with a defective performance on the ECAS-Memory (p = 0.025). No other BI-related features affected other ECAS performances.

DISCUSSION: In ALS, the occurrence of BI itself, while neither its specific features nor its presence at onset, might selectively represent a risk factor for executive impairment, whilst its severity might be associated with memory deficits.}, } @article {pmid37547466, year = {2023}, author = {Vinciguerra, C and Di Fonzo, A and Monfrini, E and Ronchi, D and Cuoco, S and Piscosquito, G and Barone, P and Pellecchia, MT}, title = {Case report: Asp194Ala variant in MFN2 is associated with ALS-FTD in an Italian family.}, journal = {Frontiers in genetics}, volume = {14}, number = {}, pages = {1235887}, pmid = {37547466}, issn = {1664-8021}, abstract = {Background: MFN2 gene encodes the protein Mitofusin 2, involved in essential mitochondrial functions such as fusion, trafficking, turnover, and cellular interactions. We describe a family carrying a novel MFN2 mutation associated with ALS-frontotemporal dementia (FTD) clinical phenotype in the mother and Charcot-Marie-Tooth disease type 2A (CMT2A) in her son. Case presentation: The mother, a 67-year-old woman, referred to us for a three year-history of mood disturbance and gait impairment, and a more recent hypophonia, dysarthria, dysphagia, and diffuse muscle wasting. Family history was positive for psychiatric disorders and gait disturbances. Brain 18F-FDG PET showed severe hypometabolism in the fronto-temporal brain cortex bilaterally. Electrodiagnostic studies (EDX) showed severe motor axonopathy in the bulbar, cervical and lumbosacral districts. Her 41-year-old son had a history of mood depression and sensory disturbances in the limbs, along with mild muscle wasting, weakness, and reduced reflexes. Nerve conduction studies revealed a moderate sensory-motor polyneuropathy, while brain MRI was normal. Whole exome sequencing of the patients' DNA identified the novel MFN2 (NM_014874.4) variant c.581A>C p.(Asp194Ala). Conclusion: Our findings provide evidence of heterogenous clinical manifestations in family members sharing the same MFN2 molecular defect. Additionally, we present the first documented case of ASL-FTD associated with an MFN2 mutation, thereby expanding the range of MFN-related disorders. Further research involving larger cohorts of patients will be needed to better understand the role of MFN2 as a contributing gene in the development of ALS-FTD.}, } @article {pmid37546945, year = {2023}, author = {Syed, SA and Singh, J and Elkholy, H and Palavra, IR and Tomicevic, M and Eric, AP and da Costa, MP and Guloksuz, S and Radhakrishnan, R}, title = {International perspective on physician knowledge, attitude and practices related to medical cannabis.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, pmid = {37546945}, support = {R01 DA054314/DA/NIDA NIH HHS/United States ; R21 AT010763/AT/NCCIH NIH HHS/United States ; R21 DA054491/DA/NIDA NIH HHS/United States ; }, abstract = {BACKGROUND: The trends of recreational use of cannabis and use of cannabis for medical indications (i.e. "medical cannabis") have grown in recent years. Despite that, there is still limited scientific evidence to guide clinical decision-making and the strength of evidence for the medical use of cannabis is currently considered to be low. In contrast, there's growing evidence for negative health outcomes related to use of cannabis. In this rapidly shifting landscape, the role of physician's attitudes regarding the therapeutic value of cannabis has become essential. This study aimed to characterize knowledge/experience, attitudes, and potential predictors of clinical practice regarding medical cannabis.

METHODS: We conducted a cross-sectional survey of physicians from 17 countries between 2016-2018. The survey comprised of 28 questions designed to explore physician knowledge, attitude, and practices regarding the use of medical cannabis. Descriptive statistics were used to examine willingness to recommend medical cannabis for medical and psychiatric indications, followed by regression analysis to identify predictors of physician willingness to recommend medical cannabis.

RESULTS: A total of 323 physicians responded to the survey. Mean age was 35.4± 9.5 years, with 10.04 ±8.6 years of clinical experience. 53 percent of physicians were women. Clinical experience with medical cannabis was overall limited (51.4% noted never having recommended medical cannabis; 33% noted inadequate knowledge regarding medical cannabis). Overall willingness to recommend medical cannabis was highest for chemotherapy-induced nausea, refractory chronic neuropathic pain, and spasticity in amyotropic lateral sclerosis (ALS).

CONCLUSION: This international study examining knowledge, attitudes and practices related to medical cannabis among physicians revealed that there are significant gaps in domain-specific knowledge related to medical cannabis. There is wide variability in willingness to recommend medical cannabis that is not consistent with the current strength of evidence. This study thus highlights the need for greater education related to domain-specific knowledge about medical cannabis.}, } @article {pmid37545643, year = {2023}, author = {Brunette, S and Sharma, A and Bell, R and Puente, L and Megeney, LA}, title = {Caspase 3 exhibits a yeast metacaspase proteostasis function that protects mitochondria from toxic TDP43 aggregates.}, journal = {Microbial cell (Graz, Austria)}, volume = {10}, number = {8}, pages = {157-169}, pmid = {37545643}, issn = {2311-2638}, abstract = {Caspase 3 activation is a hallmark of cell death and there is a strong correlation between elevated protease activity and evolving pathology in neurodegenerative disease, such as amyotrophic lateral sclerosis (ALS). At the cellular level, ALS is characterized by protein aggregates and inclusions, comprising the RNA binding protein TDP-43, which are hypothesized to trigger pathogenic activation of caspase 3. However, a growing body of evidence indicates this protease is essential for ensuring cell viability during growth, differentiation and adaptation to stress. Here, we explored whether caspase 3 acts to disperse toxic protein aggregates, a proteostasis activity first ascribed to the distantly related yeast metacaspase ScMCA1. We demonstrate that human caspase 3 can functionally substitute for the ScMCA1 and limit protein aggregation in yeast, including TDP-43 inclusions. Proteomic analysis revealed that disrupting caspase 3 in the same yeast substitution model resulted in detrimental TDP-43/mitochondrial protein associations. Similarly, suppression of caspase 3, in either murine or human skeletal muscle cells, led to accumulation of TDP-43 aggregates and impaired mitochondrial function. These results suggest that caspase 3 is not inherently pathogenic, but may act as a compensatory proteostasis factor, to limit TDP-43 protein inclusions and protect organelle function in aggregation related degenerative disease.}, } @article {pmid37545536, year = {2023}, author = {Ramachandran, S and Grozdanov, V and Leins, B and Kandler, K and Witzel, S and Mulaw, M and Ludolph, AC and Weishaupt, JH and Danzer, KM}, title = {Low T-cell reactivity to TDP-43 peptides in ALS.}, journal = {Frontiers in immunology}, volume = {14}, number = {}, pages = {1193507}, pmid = {37545536}, issn = {1664-3224}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism ; CD8-Positive T-Lymphocytes/metabolism ; DNA-Binding Proteins/metabolism ; Interleukin-2 ; }, abstract = {BACKGROUND: Dysregulation of the immune system in amyotrophic lateral sclerosis (ALS) includes changes in T-cells composition and infiltration of T cells in the brain and spinal cord. Recent studies have shown that cytotoxic T cells can directly induce motor neuron death in a mouse model of ALS and that T cells from ALS patients are cytotoxic to iPSC-derived motor neurons from ALS patients. Furthermore, a clonal expansion to unknown epitope(s) was recently found in familial ALS and increased peripheral and intrathecal activation of cytotoxic CD8[+] T cells in sporadic ALS.

RESULTS: Here, we show an increased activation of peripheral T cells from patients with sporadic ALS by IL-2 treatment, suggesting an increase of antigen-experienced T cells in ALS blood. However, a putative antigen for T-cell activation in ALS has not yet been identified. Therefore, we investigated if peptides derived from TDP-43, a key protein in ALS pathogenesis, can act as epitopes for antigen-mediated activation of human T cells by ELISPOT and flow cytometry. We found that TDP-43 peptides induced only a weak MHCI or MHCII-restricted activation of both naïve and antigen-experienced T cells from healthy controls and ALS patients. Interestingly, we found less activation in T cells from ALS patients to TDP-43 and control stimuli. Furthermore, we found no change in the levels of naturally occurring auto-antibodies against full-length TDP-43 in ALS.

CONCLUSION: Our data suggests a general increase in antigen-experienced T cells in ALS blood, measured by in-vitro culture with IL-2 for 14 days. Furthermore, it suggests that TDP-43 is a weak autoantigen.}, } @article {pmid37545133, year = {2023}, author = {Correa-Arrieta, C and Ortiz-Corredor, F and Castellar-Leones, S and Sánchez-Peñarete, D}, title = {Slowly progressive late-onset spinal muscular atrophy Finkel-type related to p.Pro56Ser VABP mutation in Colombia.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {}, number = {}, pages = {1-3}, doi = {10.1080/21678421.2023.2241881}, pmid = {37545133}, issn = {2167-9223}, abstract = {Late-onset spinal muscular atrophy associated with the VAPB gene is a slowly progressing, adult-onset, lower motor neuron disease with an autosomal dominant inheritance pattern. We present a male with progressive weakness beginning at age 44, predominantly in the proximal legs, fasciculations, and gait disturbance, with similar clinical syndrome in his mother. On physical examination, he presented weakness in 4 extremities, predominantly proximal, with atrophy and areflexia. The genetic study identified the c.166C > T mutation in the VAPB gene. The P56S mutation of the VAPB gene is associated with adult-onset spinal muscular atrophy and amyotrophic lateral sclerosis; It has been reported in different countries, although the prevalence is higher in Brazil, related to Portuguese migration. Clinically, the patients present with late-onset ALS or SMA. The disease usually onset in the fifth decade of life as progressive weakness, predominantly proximal in the lower extremities, without bulbar or respiratory involvement.}, } @article {pmid37545108, year = {2023}, author = {Portley, M and Sherer, C and Wu, T and Farren, J and Danielian, LE and Scholz, SW and Traynor, BJ and Ward, ME and Haselhuhn, T and Snyder, A and Kwan, JY}, title = {Cognitive determinants of decisional capacity in neurodegenerative disorders.}, journal = {Annals of clinical and translational neurology}, volume = {10}, number = {10}, pages = {1816-1823}, pmid = {37545108}, issn = {2328-9503}, support = {K24 AG000949/AG/NIA NIH HHS/United States ; Z01 AG000949/ImNIH/Intramural NIH HHS/United States ; }, mesh = {United States ; Humans ; *Mental Competency/psychology ; Informed Consent/psychology ; Cross-Sectional Studies ; *Frontotemporal Dementia/diagnosis ; Cognition ; }, abstract = {OBJECTIVE: Cognitive contributions to decisional capacity are complex and not well understood. Capacity to consent for research has been linked to executive function, but executive function assessment tools are imperfect. In this study, we examine the relationship between decisional capacity and a newly developed executive function composite score and determine whether cognitive performance can predict impaired decisional capacity.

METHODS: This is a cross sectional study of participants at the National Institutes of Health with frontotemporal dementia-amyotrophic lateral sclerosis spectrum disorders enrolled between 2017 and 2022. A structured interview tool was used to ascertain research decisional capacity. Study participant Uniform Data Set (v3.0) executive function (UDS3-EF) composite score, Clinical Dementia Rating Scale©, and Neuropsychiatric Inventory was determined.

RESULTS: A decrease in UDS3-EF composite score significantly increased the odds of impaired decisional capacity (OR = 2.92, 95% CI [1.66-5.13], p = 0.0002). Executive function was most impaired in frontotemporal dementia (-2.86, SD = 1.26) and least impaired in amyotrophic lateral sclerosis (-0.52, SD = 1.25) participants. The UDS3-EF composite score was also strongly correlated to the Clinical Dementia Rating Scale©.

INTERPRETATION: Decisional capacity is intrinsically related to executive function in neurodegenerative disorders, and executive dysfunction may predict a lack of decisional capacity alerting investigators of the need for additional scrutiny during the informed consent process.}, } @article {pmid37543533, year = {2024}, author = {Morishima, R and Shimizu, T and Kimura, H and Bokuda, K and Saotome, T and Nakayama, Y and Takahashi, K}, title = {High doses of opioids usage for amyotrophic lateral sclerosis patients with non-invasive ventilation.}, journal = {Acta neurologica Belgica}, volume = {124}, number = {1}, pages = {101-107}, pmid = {37543533}, issn = {2240-2993}, mesh = {Humans ; *Noninvasive Ventilation ; Respiration, Artificial ; *Amyotrophic Lateral Sclerosis/drug therapy/diagnosis ; Analgesics, Opioid/therapeutic use ; Retrospective Studies ; Morphine Derivatives ; }, abstract = {INTRODUCTION: While opioids have been found to be useful in relieving suffering in amyotrophic lateral sclerosis (ALS), there is a lack of evidence concerning how and how much to use them in practice. This study was conducted to clarify how opioids were used for patients with ALS.

METHODS: We performed a retrospective case-based analysis at a single tertiary neurology center in Tokyo from 2010 to 2018. We enrolled patients with ALS who had died before the end of 2018. We examined the opioid dosage equivalent of morphine hydrochloride and patients' clinical backgrounds, focusing on ventilatory support.

RESULTS: Morphine was administered in 110 patients with ALS, and 84 were followed up until their death. Of these 84 patients, 57 (69.9%) did not use mechanical ventilation until death (no-MV group), and 21 (22.9%) utilized only non-invasive ventilation (NIV group). Final morphine dosage in the NIV group was significantly higher (mean 65.7 mg [SD 54.6], range 10-200 mg) than in the no-MV group (mean 31.7 mg [SD 26.9], range 0-120 mg; p = 0.015, Welch's t-test). The NIV group needed psychotropic drugs more frequently than the no-MV group (62% [n = 13] vs. 35% [n = 20]).

CONCLUSION: Patients in the NIV group used opioids for a statistically significantly longer time and at a higher dose than those in the no-MV group. Symptom control with opioids alone may be difficult, and the development of multifaceted evaluation and care is desirable.}, } @article {pmid37543480, year = {2023}, author = {Petrić Howe, M and Patani, R}, title = {Nonsense-mediated mRNA decay in neuronal physiology and neurodegeneration.}, journal = {Trends in neurosciences}, volume = {46}, number = {10}, pages = {879-892}, doi = {10.1016/j.tins.2023.07.001}, pmid = {37543480}, issn = {1878-108X}, support = {/CRUK_/Cancer Research UK/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; MR/S006591/1/MRC_/Medical Research Council/United Kingdom ; MR/S006591/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Humans ; *Nonsense Mediated mRNA Decay ; *Protein Biosynthesis ; Neurons ; }, abstract = {The processes of mRNA export from the nucleus and subsequent mRNA translation in the cytoplasm are of particular relevance in eukaryotic cells. In highly polarised cells such as neurons, finely-tuned molecular regulation of these processes serves to safeguard the spatiotemporal fidelity of gene expression. Nonsense-mediated mRNA decay (NMD) is a cytoplasmic translation-dependent quality control process that regulates gene expression in a wide range of scenarios in the nervous system, including neurodevelopment, learning, and memory formation. Moreover, NMD dysregulation has been implicated in a broad range of neurodevelopmental and neurodegenerative disorders. We discuss how NMD and related aspects of mRNA translation regulate key neuronal functions and, in particular, we focus on evidence implicating these processes in the molecular pathogenesis of neurodegeneration. Finally, we discuss the therapeutic potential and challenges of targeting mRNA translation and NMD across the spectrum of largely untreatable neurological diseases.}, } @article {pmid37543426, year = {2023}, author = {Kruithof, WJ and Kruitwagen-van Reenen, E and van Eenennaam, RM and Ronda, MCM and Lamers, MJ and Visser-Meily, JMA and Beelen, A and van den Berg, LH}, title = {Multidisciplinary end-of-life care for a patient with amyotrophic lateral sclerosis requesting euthanasia.}, journal = {Lancet (London, England)}, volume = {402}, number = {10400}, pages = {484}, doi = {10.1016/S0140-6736(23)01286-2}, pmid = {37543426}, issn = {1474-547X}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy ; *Terminal Care ; *Euthanasia ; }, } @article {pmid37543304, year = {2023}, author = {Kwon, S and Lee, E and Choi, EK and Lee, SR and Oh, S and Choi, YS}, title = {Long-term outcomes of abandoned leads of cardiac implantable electronic devices.}, journal = {Heart rhythm}, volume = {20}, number = {12}, pages = {1639-1646}, doi = {10.1016/j.hrthm.2023.07.068}, pmid = {37543304}, issn = {1556-3871}, mesh = {Humans ; *Defibrillators, Implantable/adverse effects ; Retrospective Studies ; Constriction, Pathologic/etiology ; *Vascular Diseases/etiology ; *Thrombosis/etiology ; *Venous Thrombosis/etiology ; *Pacemaker, Artificial/adverse effects ; *Prosthesis-Related Infections/diagnosis/epidemiology/etiology ; }, abstract = {BACKGROUND: Evidence of the long-term outcomes of abandoned leads (ALs) in patients with cardiac implantable electronic devices (CIEDs) is scarce.

OBJECTIVE: This study aimed to investigate the long-term outcomes of ALs.

METHODS: This retrospective cohort study reviewed a single-center CIED registry of 2962 procedures performed from 1984-2018 and identified 130 patients with AL (AL group). We matched 2 controls without AL (by age, sex, device type, and device revision/removal date) to each patient with AL (n = 260) and compared CIED-related infection, venous thrombosis/stenosis, and all-cause mortality between groups using a Cox proportional hazard model analysis.

RESULTS: For a mean follow-up period of 11.2 ± 8.2 years, 14 (3.6%), 7 (1.8%), and 143 (36.7%) patients had a CIED-related infection, venous thrombosis/stenosis, or experienced all-cause mortality, respectively. The AL group had more comorbidities than the control group. Lead malfunction was the most common cause of abandonment (64.6%). After adjustment for covariates, no significant intergroup differences were noted in the risks of infection, venous thrombosis/stenosis, or all-cause mortality (adjusted hazard ratio [aHR] 2.52; 95% confidence interval [CI] 0.77-8.25; aHR 1.18; 95% CI 0.25-5.64; aHR 1.26; 95% CI 0.89-1.80, respectively). Patients with multiple ALs had increased risks of infection and all-cause mortality vs controls (aHR 8.61; 95% CI 2.13-34.84; aHR 2.42; 95% CI 1.17-5.00, respectively).

CONCLUSION: Patients with a single AL showed similar risks of CIED-related infections, venous thrombosis/stenosis, and all-cause mortality as those without ALs, whereas those with multiple ALs showed increased risks of infection and all-cause mortality.}, } @article {pmid37543248, year = {2023}, author = {Batty, GD and Kivimäki, M and Frank, P and Gale, CR and Wright, L}, title = {Systemic inflammation and subsequent risk of amyotrophic lateral sclerosis: Prospective cohort study.}, journal = {Brain, behavior, and immunity}, volume = {114}, number = {}, pages = {46-51}, pmid = {37543248}, issn = {1090-2139}, support = {MR/P023444/1/MRC_/Medical Research Council/United Kingdom ; MR/S011676/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Humans ; Female ; *Amyotrophic Lateral Sclerosis/epidemiology ; Prospective Studies ; Biomarkers ; C-Reactive Protein/metabolism ; Inflammation/complications ; }, abstract = {BACKGROUND: While systemic inflammation has been implicated in the etiology of selected neurodegenerative disorders, its role in the development of amyotrophic lateral sclerosis (ALS), a condition with high case-fatality, is untested. Accordingly, we quantified the relationship of C-reactive protein (CRP), an acute-phase reactant and marker of systemic inflammation, with subsequent ALS occurrence.

METHODS: We used data from UK Biobank, a prospective cohort study of 502,649 participants who were aged 37 to 73 years when examined at research centers between 2006 and 2010. Venous blood was collected at baseline in the full cohort and assayed for CRP, and repeat measurement was made 3-7 years later in a representative subgroup (N = 14,514) enabling correction for regression dilution. ALS was ascertained via national hospitalization and mortality registries until 2021. We computed multivariable hazard ratios with accompanying 95% confidence intervals for log-transformed CRP expressed as standard deviation and tertiles.

RESULTS: In an analytical sample of 400,884 initially ALS-free individuals (218,203 women), a mean follow-up of 12 years gave rise to 231 hospitalizations and 223 deaths ascribed to ALS. After adjustment for covariates which included health behaviors, comorbidity, and socio-economic status, a one standard deviation higher log-CRP was associated with elevated rates of both ALS mortality (hazard ratios; 95% confidence intervals: 1.32; 1.13, 1.53) and hospitalizations (1.20; 1.00, 1.39). There was evidence of dose-response effects across tertiles of CRP for both outcomes (p for trend ≤ 0.05). Correction for regression dilution led to a strengthening of the relationship with CRP for both mortality (1.62; 1.27, 2.08) and hospitalizations (1.37; 1.05, 1.76).

CONCLUSIONS: Higher levels of CRP, a blood-based biomarker widely captured in clinical practice, is associated with moderately increased future risk of amyotrophic lateral sclerosis.}, } @article {pmid37542825, year = {2023}, author = {Lee, A and Henderson, R and Arachchige, BJ and Robertson, T and McCombe, PA}, title = {Proteomic investigation of ALS motor cortex identifies known and novel pathogenetic mechanisms.}, journal = {Journal of the neurological sciences}, volume = {452}, number = {}, pages = {120753}, doi = {10.1016/j.jns.2023.120753}, pmid = {37542825}, issn = {1878-5883}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism ; *Motor Cortex/pathology ; Proteomics ; Motor Neurons/pathology ; Spinal Cord/pathology ; }, abstract = {The key pathological feature in ALS is death of motor neurones from the brain and spinal cord, but the molecular mechanisms underlying this degeneration remain unknown. Quantifying the motor cortex proteome in autopsy brain and comparing tissues from ALS cases and non-ALS controls is critical to understanding these mechanisms. We used Sequential Window Acquisition of All Theoretical Mass Spectra (SWATH-MS) to characterize the proteomes of the motor cortex from ALS cases (n = 8) and control subjects (n = 8). A total of 1427 proteins were identified at a critical local false discovery rate < 5%; 187 of these exhibited significant expression differences between ALS cases and controls. Of these, 91 proteins were significantly upregulated and 96 proteins were significantly downregulated. Bioinformatics analysis revealed that these proteins are involved in molecular transport, protein trafficking, free radical scavenging, lipid metabolism, cell death and survival, nucleic acid metabolism, inflammatory response or amino acid metabolism and carbohydrate metabolism. Differentially expressed proteins were subjected to pathway analysis. This revealed abnormalities in pathways involving mitochondrial function, sirtuin signaling, oxidative phosphorylation, glycolysis, phagosome maturation, SNARE signaling, redox regulation and several others. Core analysis revealed mitochondrial dysfunction to be the top canonical pathway. The top-enriched networks involved JNK activation and inhibition of AKT signaling, suggesting that disruption of these signaling pathways could lead to demise of motor neurons in the ALS motor cortex.}, } @article {pmid37541304, year = {2023}, author = {Zhou, Q and Zhang, X and Wu, Y and Jiang, X and Li, T and Chen, M and Ni, L and Diao, G}, title = {Polyoxometalates@Metal-Organic Frameworks Derived Bimetallic Co/Mo2 C Nanoparticles Embedded in Carbon Nanotube-Interwoven Hierarchically Porous Carbon Polyhedron Composite as a High-Efficiency Electrocatalyst for Al-S Batteries.}, journal = {Small (Weinheim an der Bergstrasse, Germany)}, volume = {19}, number = {48}, pages = {e2304515}, doi = {10.1002/smll.202304515}, pmid = {37541304}, issn = {1613-6829}, support = {21971221//National Natural Science Foundation of China/ ; 21401162//National Natural Science Foundation of China/ ; 21773203//National Natural Science Foundation of China/ ; KYCX22_3467//Postgraduate Research & Practice Innovation Program of Jiangsu Province/ ; yzuxk202010//Yangzhou University Interdisciplinary Research Foundation for Chemistry Discipline/ ; //High-Level Entrepreneurial and Innovative Talents Program of Jiangsu/ ; //"Qing Lan Project" in Colleges and Universities of Jiangsu Province/ ; //Lvyangjinfeng Talent Program of Yangzhou/ ; }, abstract = {Al-S battery (ASB) is a promising energy storage device, notable for its safety, crustal abundance, and high theoretical energy density. However, its development faces challenges due to slow reaction kinetics and poor reversibility. The creation of a multifunctional cathode material that can both adsorb polysulfides and accelerate their conversion is key to advancing ASB. Herein, a composite composed of polyoxometalate nanohybridization-derived Mo2 C and N-doped carbon nanotube-interwoven polyhedrons (Co/Mo2 C@NCNHP) is proposed for the first time as an electrochemical catalyst in the sulfur cathode. This composite improves the utilization and conductivity of sulfur within the cathode. DFT calculations and experimental results indicate that Co enables the chemisorption of polysulfides while Mo2 C catalyzes the reduction reaction of long-chain polysulfides. X-ray photoelectron spectroscopy (XPS) and in situ UV analysis reveal the different intermediates of Al polysulfide species in Co/Mo2 C@NCNHP during discharging/charging. As a cathode material for ASB, Co/Mo2 C@NCNHP@S composite can deliver a discharge-charge voltage hysteresis of 0.75 V with a specific capacity of 370 mAh g[-1] after 200 cycles at 1A g[-1] .}, } @article {pmid37540751, year = {2023}, author = {Oiwa, K and Watanabe, S and Onodera, K and Iguchi, Y and Kinoshita, Y and Komine, O and Sobue, A and Okada, Y and Katsuno, M and Yamanaka, K}, title = {Monomerization of TDP-43 is a key determinant for inducing TDP-43 pathology in amyotrophic lateral sclerosis.}, journal = {Science advances}, volume = {9}, number = {31}, pages = {eadf6895}, pmid = {37540751}, issn = {2375-2548}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/pathology ; DNA-Binding Proteins/genetics/metabolism ; Inclusion Bodies/metabolism ; Motor Neurons/metabolism ; }, abstract = {The cytoplasmic aggregation of TAR DNA binding protein-43 (TDP-43), also known as TDP-43 pathology, is the pathological hallmark of amyotrophic lateral sclerosis (ALS). However, the mechanism underlying TDP-43 cytoplasmic mislocalization and subsequent aggregation remains unclear. Here, we show that TDP-43 dimerization/multimerization is impaired in the postmortem brains and spinal cords of patients with sporadic ALS and that N-terminal dimerization-deficient TDP-43 consists of pathological inclusion bodies in ALS motor neurons. Expression of N-terminal dimerization-deficient mutant TDP-43 in Neuro2a cells and induced pluripotent stem cell-derived motor neurons recapitulates TDP-43 pathology, such as Nxf1-dependent cytoplasmic mislocalization and aggregate formation, which induces seeding effects. Furthermore, TDP-DiLuc, a bimolecular luminescence complementation reporter assay, could detect decreased N-terminal dimerization of TDP-43 before TDP-43 pathological changes caused by the transcription inhibition linked to aberrant RNA metabolism in ALS. These findings identified TDP-43 monomerization as a critical determinant inducing TDP-43 pathology in ALS.}, } @article {pmid37540049, year = {2023}, author = {Ko, JI and Choi, SJ and Yoo, SH and Cho, B and Kim, MS and Kim, KH and Lee, SY}, title = {Epidemiology and characteristics of emergency department utilization by patients with amyotrophic lateral sclerosis in Korea from 2016 to 2020: A nationwide study.}, journal = {Muscle & nerve}, volume = {68}, number = {4}, pages = {451-459}, doi = {10.1002/mus.27952}, pmid = {37540049}, issn = {1097-4598}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/epidemiology/therapy ; Cross-Sectional Studies ; Emergency Service, Hospital ; *Respiratory Insufficiency/epidemiology/etiology/therapy ; Dyspnea ; Republic of Korea/epidemiology ; Retrospective Studies ; }, abstract = {INTRODUCTION/AIMS: Patients with amyotrophic lateral sclerosis (ALS) inevitably visit the emergency department (ED) due to their increased risk of respiratory failure and mobility limitations. However, nationwide data on ED visits by patients with ALS are limited. This study investigated the characteristics of patients with ALS-related ED visits.

METHODS: We conducted a cross-sectional study from 2016 to 2020, utilizing a nationwide ED database. The total number of patients with ALS who visited the ED and their primary reasons for visiting/diagnoses were analyzed.

RESULTS: In total, 6036 visits to the ED were made by patients with ALS. Of these, 41.8% arrived by ambulance and 27.7% spent >9 h in the ED. Following ED treatment, 57.4% were hospitalized, including 19.3% admitted to the intensive care unit (ICU) and 5.4% who died in the hospital. The primary reasons for ALS-related ED visits were dyspnea (35.2%), feeding tube problems (10.1%), fever (7.8%), and mental status changes (3.6%). The most common diagnoses were pneumonia (14.5%), respiratory failure (5.7%), dyspnea (5.5%), aspiration pneumonia (4.3%), and tracheostomy complications (3.4%).

DISCUSSION: Reasons for ED visits for patients with ALS include acute respiratory distress, as well as concerns related to tube feeding and tracheostomy. To reduce the risk of patients with ALS requiring ED visits, it is essential to ensure the provision of timely respiratory support and high-quality home-based medical care teams that can support and address patients before their condition deteriorates.}, } @article {pmid37539949, year = {2023}, author = {Raymond, J and Punjani, R and Larson, T and Berry, JD and Horton, DK and Mehta, P}, title = {Comparing Amyotrophic lateral sclerosis (ALS) patient characteristics from the National ALS Registry and the Massachusetts ALS Registry, data through 2015.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {}, number = {}, pages = {1-8}, pmid = {37539949}, issn = {2167-9223}, support = {CC999999/ImCDC/Intramural CDC HHS/United States ; }, abstract = {OBJECTIVE: To compare, for completeness, ALS patients identified in the National ALS Registry (National Registry) from MA to those in the Massachusetts ALS Registry (MA Registry) through 2015.

METHODS: Sensitivity analyses were conducted to determine the completeness among patients reported in both registries. Patients were matched on first and last name, month and year of birth, sex, as well as Soundex name matching. Demographics for matching and nonmatching ALS patients were also examined using bivariate analyses and logistic regression.

RESULTS: There were 1,042 ALS patients in the MA Registry, and 642 patients matched (61.6%) in the National Registry. Sensitivity analyses found the National Registry had a sensitivity of 87.7% and specificity of 60%. For these matched patients, 522 (81.2%) came from Medicare. Of the 400 patients in the MA Registry not matched to the National Registry, 11.1% were nonwhite, compared to 6.0% in the matched group) (p = 0.0091) and 59.2% were diagnosed before age 60, compared to 28.6% in the matched group (p < 0.0001). Multivariate logistic regression analysis showed being an ALS case (p < 0.0001) and having an ALS diagnosis at age 60 or later (p < 0.0001) were associated with being more likely to match between the two registries.

CONCLUSIONS: These findings show that ALS's non-notifiable condition status at the national level continues to pose a challenge in identifying all ALS patients. This analysis also showed missing cases at the state level even with a reporting statute. Additional strategies are needed for better patient-ascertainment to quantify all ALS patients in the U.S.}, } @article {pmid37537908, year = {2023}, author = {Tandan, R and Howard, D and Matthews, DE}, title = {Increased total daily energy expenditure in mild to moderate ALS: greater contribution from physical activity energy expenditure than hyper-metabolism.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {}, number = {}, pages = {1-8}, doi = {10.1080/21678421.2023.2240377}, pmid = {37537908}, issn = {2167-9223}, abstract = {Objective: It is unknown whether the relative contribution to energy imbalance in amyotrophic lateral sclerosis (ALS) is due to decreased energy intake, or increased energy expenditure from hyper-metabolism and/or physical activity, or both. Methods: We studied 10 free-living sporadic ALS subjects with mild to moderate disease and 10 matched healthy controls to address this question. We estimated energy intake by 24-h recall in ALS subjects and three-day food diary in all. We estimated body composition by dual energy X-ray absorptiometry and resting metabolic rate by indirect calorimetry; and measured total daily energy expenditure (TEE) and physical activity-energy expenditure using doubly labeled water. Results: Daily energy intake was no different between ALS subjects and controls. Despite lower fat-free mass, unadjusted TEE was higher in ALS subjects than controls (2844 ± 319 vs. 2505 ± 261 kcal/d, p = 0.005 by paired t-test). Compared to controls, hyper-metabolism occurred in 80% of ALS subjects. Physical activity-energy expenditure was higher in ALS subjects than controls (718 ± 262 kcal/d vs. 487 ± 196 kcal/d, p = 0.04). In controls, energy intake matched TEE; in ALS subjects TEE was higher than energy intake. Conclusions: We found higher TEE in ALS subjects than controls, with larger contribution to difference from physical activity-energy expenditure than hyper-metabolism. Although daily energy intake in ALS subjects was similar to that in controls, they were unable to compensate for increased energy needs. To accurately determine energy balance and optimize nutrition in ALS, future studies should consider measuring energy intake, energy expenditure, and physical activity.}, } @article {pmid37536971, year = {2023}, author = {Crook-Rumsey, M and Daniels, SJC and Abulikemu, S and Lai, H and Rapeaux, A and Hadjipanayi, C and Soreq, E and Li, LM and Bashford, J and Jeyasingh-Jacob, J and Gruia, DC and Lambert, D and Weil, R and Hampshire, A and Sharp, DJ and Haar, S}, title = {Multicohort cross-sectional study of cognitive and behavioural digital biomarkers in neurodegeneration: the Living Lab Study protocol.}, journal = {BMJ open}, volume = {13}, number = {8}, pages = {e072094}, pmid = {37536971}, issn = {2044-6055}, support = {UKDRI-7004/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Humans ; Cross-Sectional Studies ; Activities of Daily Living ; *Neurodegenerative Diseases/diagnosis ; *Cognitive Dysfunction/psychology ; Cognition ; Biomarkers ; Observational Studies as Topic ; }, abstract = {INTRODUCTION AND AIMS: Digital biomarkers can provide a cost-effective, objective and robust measure for neurological disease progression, changes in care needs and the effect of interventions. Motor function, physiology and behaviour can provide informative measures of neurological conditions and neurodegenerative decline. New digital technologies present an opportunity to provide remote, high-frequency monitoring of patients from within their homes. The purpose of the living lab study is to develop novel digital biomarkers of functional impairment in those living with neurodegenerative disease (NDD) and neurological conditions.

METHODS AND ANALYSIS: The Living Lab study is a cross-sectional observational study of cognition and behaviour in people living with NDDs and other, non-degenerative neurological conditions. Patients (n≥25 for each patient group) with dementia, Parkinson's disease, amyotrophic lateral sclerosis, mild cognitive impairment, traumatic brain injury and stroke along with controls (n≥60) will be pragmatically recruited. Patients will carry out activities of daily living and functional assessments within the Living Lab. The Living Lab is an apartment-laboratory containing a functional kitchen, bathroom, bed and living area to provide a controlled environment to develop novel digital biomarkers. The Living Lab provides an important intermediary stage between the conventional laboratory and the home. Multiple passive environmental sensors, internet-enabled medical devices, wearables and electroencephalography (EEG) will be used to characterise functional impairments of NDDs and non-NDD conditions. We will also relate these digital technology measures to clinical and cognitive outcomes.

ETHICS AND DISSEMINATION: Ethical approvals have been granted by the Imperial College Research Ethics Committee (reference number: 21IC6992). Results from the study will be disseminated at conferences and within peer-reviewed journals.}, } @article {pmid37535076, year = {2023}, author = {Yang, X and Zhang, Y and Luo, JX and Zhu, T and Ran, Z and Mu, BR and Lu, MH}, title = {Targeting mitophagy for neurological disorders treatment: advances in drugs and non-drug approaches.}, journal = {Naunyn-Schmiedeberg's archives of pharmacology}, volume = {396}, number = {12}, pages = {3503-3528}, pmid = {37535076}, issn = {1432-1912}, mesh = {Animals ; Humans ; Mitophagy/physiology ; Mitochondria/metabolism ; *Parkinson Disease/metabolism ; *Alzheimer Disease/metabolism ; }, abstract = {Mitochondria serve as a vital energy source for nerve cells. The mitochondrial network also acts as a defense mechanism against external stressors that can threaten the stability of the nervous system. However, excessive accumulation of damaged mitochondria can lead to neuronal death. Mitophagy is an essential pathway in the mitochondrial quality control system and can protect neurons by selectively removing damaged mitochondria. In most neurological disorders, dysfunctional mitochondria are a common feature, and drugs that target mitophagy can improve symptoms. Here, we reviewed the role of mitophagy in Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease, stroke, and traumatic brain injuries. We also summarized drug and non-drug approaches to promote mitophagy and described their therapeutic role in neurological disorders in order to provide valuable insight into the potential therapeutic agents available for neurological disease treatment. However, most studies on mitophagy regulation are based on preclinical research using cell and animal models, which may not accurately reflect the effects in humans. This poses a challenge to the clinical application of drugs targeting mitophagy. Additionally, these drugs may carry the risk of intolerable side effects and toxicity. Future research should focus on the development of safer and more targeted drugs for mitophagy.}, } @article {pmid37534756, year = {2023}, author = {Spargo, TP and Opie-Martin, S and Hunt, GP and Kalia, M and Al Khleifat, A and Topp, SD and Shaw, CE and Al-Chalabi, A and Iacoangeli, A and , }, title = {SOD1-ALS-Browser: a web-utility for investigating the clinical phenotype in SOD1 amyotrophic lateral sclerosis.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {}, number = {}, pages = {1-10}, doi = {10.1080/21678421.2023.2236650}, pmid = {37534756}, issn = {2167-9223}, support = {MR/L501529/1/MRC_/Medical Research Council/United Kingdom ; }, abstract = {Objective: Variants in the superoxide dismutase (SOD1) gene are among the most common genetic causes of amyotrophic lateral sclerosis. Reflecting the wide spectrum of putatively deleterious variants that have been reported to date, it has become clear that SOD1-linked ALS presents a highly variable age at symptom onset and disease duration.Methods: Here we describe an open access web tool for comparative phenotype analysis in ALS: https://sod1-als-browser.rosalind.kcl.ac.uk/. The tool contains a built-in dataset of clinical information from 1383 people with ALS harboring a SOD1 variant resulting in one of 162 unique amino acid sequence alterations and from a non-SOD1 comparator ALS cohort of 13,469 individuals. We present two examples of analyses possible with this tool, testing how the ALS phenotype relates to SOD1 variants that alter amino acid residue hydrophobicity and to distinct variants at the 94[th] residue of SOD1, where six are sampled.Results and conclusions: The tool provides immediate access to the datasets and enables bespoke analysis of phenotypic trends associated with different protein variants, including the option for users to upload their own datasets for integration with the server data. The tool can be used to study SOD1-ALS and provides an analytical framework to study the differences between other user-uploaded ALS groups and our large reference database of SOD1 and non-SOD1 ALS. The tool is designed to be useful for clinicians and researchers, including those without programming expertise, and is highly flexible in the analyses that can be conducted.}, } @article {pmid37534731, year = {2023}, author = {Tian, Y and Ma, G and Li, H and Zeng, Y and Zhou, S and Wang, X and Shan, S and Xu, Y and Xiong, J and Cheng, G}, title = {Shared Genetics and Comorbid Genes of Amyotrophic Lateral Sclerosis and Parkinson's Disease.}, journal = {Movement disorders : official journal of the Movement Disorder Society}, volume = {38}, number = {10}, pages = {1813-1821}, doi = {10.1002/mds.29572}, pmid = {37534731}, issn = {1531-8257}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics ; *Parkinson Disease/genetics ; Genome-Wide Association Study ; Genetic Predisposition to Disease/genetics ; Comorbidity ; Polymorphism, Single Nucleotide/genetics ; Mendelian Randomization Analysis ; Membrane Proteins/genetics ; ADAM Proteins/genetics ; Transcription Factors/genetics ; DNA Repair Enzymes/genetics ; }, abstract = {BACKGROUND: Comorbidity exists between amyotrophic lateral sclerosis (ALS) and Parkinson's disease (PD), but the role of genetic factors is unclear.

OBJECTIVE: We aim to investigate genetic correlation, causal relationship, and comorbid genes between ALS and PD.

METHODS: Leveraging the largest genome-wide association study data (ALS: 27,205 cases, 110,881 controls; PDG: 33,674 cases, 449,056 controls), we used linkage disequilibrium score regression and Mendelian randomization analysis for genetic correlation and causal inference. We performed genome-wide cross-trait analysis via Multi-Trait Analysis of Genome-Wide Association Studies and Cross-Phenotype Association to identify specific single-nucleotide polymorphisms, followed by functional mapping and annotation. Integrating expression quantitative trait loci data from 13 brain regions, we conducted a transcriptome-wide association study via functional summary-based imputation and joint-tissue imputation to explore comorbid genes, followed by pathway enrichment analysis.

RESULTS: We found that PD positively correlates with ALS (rg  = 0.144, P = 0.026) and confers a causal effect (odds ratio = 1.09, 95% confidence interval: 1.03-1.15, P = 3.00 × 10[-3]). We identified nine single-nucleotide polymorphisms (eight new), associating with three risk loci (chromosomes 4, 10, and 17) and seven genes (TMEM175, MAPT, NSF, LRRC37A2, ARHGAP27, GAK, and FGFRL1). In transcriptome-wide association study analysis, we showed six previously unreported pleiotropic genes (KANSL1, ARL17B, EFNA1, WNT3, ERCC8, and ADAM15), and we found these candidate genes are mainly enriched in negative regulation of neuron projection development (GO:0010977).

CONCLUSIONS: Our work demonstrates shared genetic architecture between ALS and PD, reports new pleiotropic genes, and sheds light on the comorbid mechanism. © 2023 International Parkinson and Movement Disorder Society.}, } @article {pmid37534581, year = {2023}, author = {Lebœuf, M and Vargas-Abonce, SE and Pezé-Hedsieck, E and Dupont, E and Jimenez-Alonso, L and Moya, KL and Prochiantz, A}, title = {ENGRAILED-1 transcription factor has a paracrine neurotrophic activity on adult spinal α-motoneurons.}, journal = {EMBO reports}, volume = {24}, number = {8}, pages = {e56525}, pmid = {37534581}, issn = {1469-3178}, support = {339379/ERC_/European Research Council/International ; }, mesh = {Mice ; Animals ; *Transcription Factors/genetics/metabolism ; *Motor Neurons/metabolism ; Spinal Cord/metabolism ; Homeodomain Proteins/genetics/metabolism ; Interneurons/metabolism ; }, abstract = {Several homeoprotein transcription factors transfer between cells and regulate gene expression, protein translation, and chromatin organization in recipient cells. ENGRAILED-1 is one such homeoprotein expressed in spinal V1 interneurons that synapse on α-motoneurons. Neutralizing extracellular ENGRAILED-1 by expressing a secreted single-chain antibody blocks its capture by spinal motoneurons resulting in α-motoneuron loss and limb weakness. A similar but stronger phenotype is observed in the Engrailed-1 heterozygote mouse, confirming that ENGRAILED-1 exerts a paracrine neurotrophic activity on spinal cord α-motoneurons. Intrathecal injection of ENGRAILED-1 leads to its specific internalization by spinal motoneurons and has long-lasting protective effects against neurodegeneration and weakness. Midbrain dopaminergic neurons express Engrailed-1 and, similarly to spinal cord α-motoneurons, degenerate in the heterozygote. We identify genes expressed in spinal cord motoneurons whose expression changes in mouse Engrailed-1 heterozygote midbrain neurons. Among these, p62/SQSTM1 shows increased expression during aging in spinal cord motoneurons in the Engrailed-1 heterozygote and upon extracellular ENGRAILED-1 neutralization. We conclude that ENGRAILED-1 might regulate motoneuron aging and has non-cell-autonomous neurotrophic activity.}, } @article {pmid37533065, year = {2023}, author = {Jones, BD and Wilkins, JLM and Schram, ÁB and Gladman, T and Kenwright, D and A Lucio-Ramírez, C}, title = {Validating a measure of motivational climate in health science courses.}, journal = {BMC medical education}, volume = {23}, number = {1}, pages = {548}, pmid = {37533065}, issn = {1472-6920}, mesh = {Humans ; *Motivation ; Schools ; *Students, Medical ; Achievement ; Surveys and Questionnaires ; }, abstract = {PURPOSE: The aim of the study was to examine the validity evidence for the 19-item form of the MUSIC Model of Academic Motivation Inventory (College Student version) within health science schools in three different countries. The MUSIC Inventory includes five scales that assess the motivational climate by measuring students' perceptions related to five separate constructs: empowerment, usefulness, success, interest, and caring.

BACKGROUND: The 26-item form of the MUSIC Inventory has been validated for use with undergraduate students and with students in professional schools, including students at a veterinary medicine school, a pharmacy school, and a medical school. A 19-item form of the MUSIC Inventory has also been validated for use with undergraduate students, but it has not yet been validated for use with medical school students. The purpose of this study was to provide validity evidence for the use of the 19-item form in heath science schools in three different countries to determine if this version is acceptable for use in different cultures. If validated, this shorter form of the MUSIC Inventory would provide more differentiation between the Interest and Usefulness scales and could reduce respondent fatigue.

METHODOLOGY: Cook et al's [1] practical guidelines were followed to implement Kane's [2] validity framework as a means to examine the evidence of validity through scoring inferences, generalization inferences, and extrapolation inferences. Students (n = 667) in health science schools within three countries were surveyed.

RESULTS: The results produced evidence to support all five hypotheses related to scoring, generalization, and extrapolation inferences.

CONCLUSIONS: Scores from the 19-item form of the MUSIC Inventory are valid for use in health science courses within professional schools in different countries. Therefore, the MUSIC Inventory can be used in these schools to assess students' perceptions of the motivational climate.}, } @article {pmid37532939, year = {2023}, author = {Arseni, D and Chen, R and Murzin, AG and Peak-Chew, SY and Garringer, HJ and Newell, KL and Kametani, F and Robinson, AC and Vidal, R and Ghetti, B and Hasegawa, M and Ryskeldi-Falcon, B}, title = {TDP-43 forms amyloid filaments with a distinct fold in type A FTLD-TDP.}, journal = {Nature}, volume = {620}, number = {7975}, pages = {898-903}, pmid = {37532939}, issn = {1476-4687}, support = {MC_UP_1201/25/MRC_/Medical Research Council/United Kingdom ; P30 AG010133/AG/NIA NIH HHS/United States ; RF1 AG071177/AG/NIA NIH HHS/United States ; P30 AG072976/AG/NIA NIH HHS/United States ; U01 NS110437/NS/NINDS NIH HHS/United States ; R01 AG071177/AG/NIA NIH HHS/United States ; }, mesh = {Humans ; Citrullination ; Cryoelectron Microscopy ; *DNA-Binding Proteins/chemistry/metabolism/ultrastructure ; *Frontotemporal Dementia/metabolism/pathology ; *Frontotemporal Lobar Degeneration/classification/metabolism/pathology ; Methylation ; }, abstract = {The abnormal assembly of TAR DNA-binding protein 43 (TDP-43) in neuronal and glial cells characterizes nearly all cases of amyotrophic lateral sclerosis (ALS) and around half of cases of frontotemporal lobar degeneration (FTLD)[1,2]. A causal role for TDP-43 assembly in neurodegeneration is evidenced by dominantly inherited missense mutations in TARDBP, the gene encoding TDP-43, that promote assembly and give rise to ALS and FTLD[3-7]. At least four types (A-D) of FTLD with TDP-43 pathology (FTLD-TDP) are defined by distinct brain distributions of assembled TDP-43 and are associated with different clinical presentations of frontotemporal dementia[8]. We previously showed, using cryo-electron microscopy, that TDP-43 assembles into amyloid filaments in ALS and type B FTLD-TDP[9]. However, the structures of assembled TDP-43 in FTLD without ALS remained unknown. Here we report the cryo-electron microscopy structures of assembled TDP-43 from the brains of three individuals with the most common type of FTLD-TDP, type A. TDP-43 formed amyloid filaments with a new fold that was the same across individuals, indicating that this fold may characterize type A FTLD-TDP. The fold resembles a chevron badge and is unlike the double-spiral-shaped fold of ALS and type B FTLD-TDP, establishing that distinct filament folds of TDP-43 characterize different neurodegenerative conditions. The structures, in combination with mass spectrometry, led to the identification of two new post-translational modifications of assembled TDP-43, citrullination and monomethylation of R293, and indicate that they may facilitate filament formation and observed structural variation in individual filaments. The structures of TDP-43 filaments from type A FTLD-TDP will guide mechanistic studies of TDP-43 assembly, as well as the development of diagnostic and therapeutic compounds for TDP-43 proteinopathies.}, } @article {pmid37532350, year = {2023}, author = {Zhao, B and Xu, X and Li, B and Qi, Z and Huang, J and Hu, A and Wang, G and Liu, X}, title = {Target-site mutation and enhanced metabolism endow resistance to nicosulfuron in a Digitaria sanguinalis population.}, journal = {Pesticide biochemistry and physiology}, volume = {194}, number = {}, pages = {105488}, doi = {10.1016/j.pestbp.2023.105488}, pmid = {37532350}, issn = {1095-9939}, mesh = {Digitaria/genetics ; Sulfonylurea Compounds/pharmacology ; Pyridines ; Mutation ; *Acetolactate Synthase/metabolism ; Enzyme Inhibitors/pharmacology ; *Herbicides/pharmacology ; Herbicide Resistance/genetics ; }, abstract = {Digitaria sanguinalis is a competitive and annual grass weed that commonly infests crops across the world. In recent years, the control of D. sanguinalis by nicosulfuron has declined in Hebei Province, China. To determine the resistance mechanisms of D. sanguinalis to nicosulfuron, a population of D. sanguinalis where nicosulfuron had failed was collected from a maize field of Hebei Province, China. Whole-plant dose-response experiments demonstrated that the resistant population (HBMT-15) displayed 6.9-fold resistance to nicosulfuron compared with the susceptible population (HBMT-5). Addition of the glutathione S-transferase (GSTs) inhibitor 4-chloro-7-nitrobenzoxadiazole (NBD-Cl) significantly reduced the resistance level of the HBMT-15 population to nicosulfuron, and the GSTs activity of the HBMT-15 population was higher than the HBMT-5 population after nicosulfuron treatment. In vitro acetolactate synthase (ALS) enzyme experiments revealed that the nicosulfuron I50 value for the HBMT-15 population was 41 times higher than that of the HBMT-5 population. An Asp376 to Glu substitution in the ALS gene was identified in the HBMT-15 population. The HBMT-15 population had a moderate (2- to 4-fold) level of cross-resistance to three other ALS inhibitors (imazethapyr, pyroxsulam, and flucarbazone‑sodium), but was susceptible to pyrithiobac‑sodium. This study demonstrated that both an Asp376 to Glu substitution in the ALS gene and GSTs-involved metabolic resistance to ALS inhibitors coexisted in a D. sanguinalis population.}, } @article {pmid37532339, year = {2023}, author = {Deng, W and Li, Y and Yao, S and Duan, Z and Yang, Q and Yuan, S}, title = {ACCase gene mutations and P450-mediated metabolism contribute to cyhalofop-butyl resistance in Eleusine indica biotypes from direct-seeding paddy fields.}, journal = {Pesticide biochemistry and physiology}, volume = {194}, number = {}, pages = {105530}, doi = {10.1016/j.pestbp.2023.105530}, pmid = {37532339}, issn = {1095-9939}, mesh = {*Eleusine/genetics ; Acetyl-CoA Carboxylase/metabolism ; Herbicide Resistance/genetics ; *Oryza/genetics/metabolism ; Mutation ; *Herbicides/pharmacology ; }, abstract = {Eleusine indica causes problems in direct-seeding rice fields across Jiangsu Province in China. Long-term application of chemical herbicides has led to the widespread evolution of resistance in E. indica. In this study, we surveyed the resistance level of cyhalofop-butyl (CyB) in 19 field-collected E. indica biotypes, and characterized its underlying resistance mechanisms. All 19 biotypes evolved moderate- to high-level resistance to CyB (from 5.8- to 171.1-fold). 18 biotypes had a target-site mechanism with Trp-1999-Ser, Trp-2027-Cys, or Asp-2078-Gly mutations, respectively. One biotype (JSSQ-1) was identified to have metabolic resistance, in which malathion pretreatment significantly reduced the CyB resistance, and cyhalofop acid was degraded 1.7- to 2.5-times faster in this biotype compared with a susceptible control. Furthermore, the JSSQ-1 biotype showed multiple resistance to acetyl-CoA carboxylase (ACCase) inhibitor metamifop (RI = 4.6) and fenoxaprop-p-ethyl (RI = 5.1), acetolactate synthase (ALS) inhibitor imazethapyr (RI = 4.1), and hydroxyphenylpyruvate dioxygenase (HPPD) inhibitor mesotrione (RI = 3.5). In addition, 11 out of 19 E. indica biotypes exhibited multiple resistance to glyphosate. This research has identified the widespread occurrence of CyB resistance in E. indica, attributed to target-site mutations or enhanced metabolism. Moreover, certain biotypes have exhibited resistance to multiple herbicides or even cross-resistance. Consequently, there is an urgent need to implement diverse weed management practices to effectively combat the proliferation of this weed in rice fields.}, } @article {pmid37532326, year = {2023}, author = {Guan, Y and Cao, S and Zou, Y and Liu, L and Yang, C and Ji, M}, title = {Enhanced metabolic ability enabled wild panicgrass (Panicum miliaceum L. var. ruderale kit.) resistance to ALS inhibitor herbicide.}, journal = {Pesticide biochemistry and physiology}, volume = {194}, number = {}, pages = {105510}, doi = {10.1016/j.pestbp.2023.105510}, pmid = {37532326}, issn = {1095-9939}, mesh = {*Panicum/metabolism ; *Herbicides/pharmacology ; Sulfonylurea Compounds/pharmacology ; Pyridines/pharmacology ; Zea mays ; Herbicide Resistance/genetics ; *Acetolactate Synthase/metabolism ; Plant Proteins/genetics ; }, abstract = {Wild panicgrass (Panicum miliaceum L. var. ruderale kit.) is an annual grass weed that primarily occurs in maize fields. Nicosulfuron is a widely used selective herbicide that effectively controls gramineous weeds in maize fields. However, owing to its long-term and extensive application, the control of P. miliaceum has been substantially reduced. The objective of this study was to determine the resistance pattern to ALS inhibitors in P. miliaceum and investigate the underlying resistance mechanisms. These are important for guiding the prevention and eradication of resistant weeds. Whole plant bioassays showed P. miliaceum had evolved high levels of resistance to nicosulfuron and multiple resistance to atrazine and mesotrione. The ALS gene sequence results indicated the absence of mutations in the resistant population. Additionally, there was no significant difference found in the inhibition rate of the ALS enzyme activity (I50) between the resistant and sensitive populations. Following the application of malathion the resistant P. miliaceum population became more sensitive to nicosulfuron. At 96 h after application of nicosulfuron, glutathione-S-transferase activity in the resistant population was significantly higher than that in the susceptible population. The study reveals that the main cause of resistance to ALS inhibitor herbicide in P. miliaceum is likely increased metabolism of herbicides. These findings may assist in devising effective strategies for preventing and eliminating resistant P. miliaceum.}, } @article {pmid37531027, year = {2023}, author = {Gomes, BC and Peixinho, N and Pisco, R and Gromicho, M and Pronto-Laborinho, AC and Rueff, J and de Carvalho, M and Rodrigues, AS}, title = {Differential Expression of miRNAs in Amyotrophic Lateral Sclerosis Patients.}, journal = {Molecular neurobiology}, volume = {60}, number = {12}, pages = {7104-7117}, pmid = {37531027}, issn = {1559-1182}, mesh = {Humans ; *MicroRNAs/genetics ; *Amyotrophic Lateral Sclerosis/genetics ; Delayed Diagnosis ; Brain ; Disease Progression ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive motor neuron disease that affects nerve cells in the brain and spinal cord, causing loss of muscle control, muscle atrophy and in later stages, death. Diagnosis has an average delay of 1 year after symptoms onset, which impairs early management. The identification of a specific disease biomarker could help decrease the diagnostic delay. MicroRNA (miRNA) expression levels have been proposed as ALS biomarkers, and altered function has been reported in ALS pathogenesis. The aim of this study was to assess the differential expression of plasma miRNAs in ALS patients and two control populations (healthy controls and ALS-mimic disorders). For that, 16 samples from each group were pooled, and then 1008 miRNAs were assessed through reverse transcription-quantitative polymerase chain reaction (RT-qPCR). From these, ten candidate miRNAs were selected and validated in 35 ALS patients, 16 ALS-mimic disorders controls and 15 healthy controls. We also assessed the same miRNAs in two different time points of disease progression. Although we were unable to determine a miRNA signature to use as disease or condition marker, we found that miR-7-2-3p, miR-26a-1-3p, miR-224-5p and miR-206 are good study candidates to understand the pathophysiology of ALS.}, } @article {pmid37529232, year = {2023}, author = {Wen, T and Zhang, Z}, title = {Cellular mechanisms of fibrin (ogen): insight from neurodegenerative diseases.}, journal = {Frontiers in neuroscience}, volume = {17}, number = {}, pages = {1197094}, pmid = {37529232}, issn = {1662-4548}, abstract = {Neurodegenerative diseases are prevalent and currently incurable conditions that progressively impair cognitive, behavioral, and psychiatric functions of the central or peripheral nervous system. Fibrinogen, a macromolecular glycoprotein, plays a crucial role in the inflammatory response and tissue repair in the human body and interacts with various nervous system cells due to its unique molecular structure. Accumulating evidence suggests that fibrinogen deposits in the brains of patients with neurodegenerative diseases. By regulating pathophysiological mechanisms and signaling pathways, fibrinogen can exacerbate the neuro-pathological features of neurodegenerative diseases, while depletion of fibrinogen contributes to the amelioration of cognitive function impairment in patients. This review comprehensively summarizes the molecular mechanisms and biological functions of fibrinogen in central nervous system cells and neurodegenerative diseases, including Alzheimer's disease, Multiple Sclerosis, Parkinson's disease, Vascular dementia, Huntington's disease, and Amyotrophic Lateral Sclerosis. Additionally, we discuss the potential of fibrinogen-related treatments in the management of neurodegenerative disorders.}, } @article {pmid37528809, year = {2023}, author = {Lee, YY and Caron-Roy, S and Turko, B and Shearer, J and Campbell, DJ and Elliott, C and Barker, D and Raine, KD and Tyminski, S and Olstad, DL}, title = {Experiences and perceived outcomes of a grocery gift card programme for households at risk of food insecurity.}, journal = {Public health nutrition}, volume = {26}, number = {11}, pages = {2460-2469}, pmid = {37528809}, issn = {1475-2727}, mesh = {Child ; Humans ; *Food Supply ; Cognition ; Family Characteristics ; Alberta ; Food Insecurity ; *Food Assistance ; }, abstract = {OBJECTIVE: This study explored programme recipients' and deliverers' experiences and perceived outcomes of accessing or facilitating a grocery gift card (GGC) programme from I Can for Kids (iCAN), a community-based programme that provides GGC to low-income families with children.

DESIGN: This qualitative descriptive study used Freedman et al's framework of nutritious food access to guide data generation and analysis. Semi-structured interviews were conducted between August and November 2020. Data were analysed using directed content analysis with a deductive-inductive approach.

PARTICIPANTS: Fifty-four participants were purposively recruited, including thirty-seven programme recipients who accessed iCAN's GGC programme and seventeen programme deliverers who facilitated it.

SETTING: Calgary, Alberta, Canada.

RESULTS: Three themes were generated from the data. First, iCAN's GGC programme promoted a sense of autonomy and dignity among programme recipients as they appreciated receiving financial support, the flexibility and convenience of using GGC, and the freedom to select foods they desired. Recipients perceived these benefits improved their social and emotional well-being. Second, recipients reported that the use of GGC improved their households' dietary patterns and food skills. Third, both participant groups identified programmatic strengths and limitations.

CONCLUSION: Programme recipients reported that iCAN's GGC programme provided them with dignified access to nutritious food and improved their households' finances, dietary patterns, and social and emotional well-being. Increasing the number of GGC provided to households on each occasion, establishing clear and consistent criteria for distributing GGC to recipients, and increasing potential donors' awareness of iCAN's GGC programme may augment the amount of support iCAN could provide to households.}, } @article {pmid37528491, year = {2023}, author = {Li, C and Lin, J and Jiang, Q and Yang, T and Xiao, Y and Huang, J and Hou, Y and Wei, Q and Cui, Y and Wang, S and Zheng, X and Ou, R and Liu, K and Chen, X and Song, W and Zhao, B and Shang, H}, title = {Genetic Modifiers of Age at Onset for Amyotrophic Lateral Sclerosis: A Genome-Wide Association Study.}, journal = {Annals of neurology}, volume = {94}, number = {5}, pages = {933-941}, doi = {10.1002/ana.26752}, pmid = {37528491}, issn = {1531-8249}, mesh = {Humans ; *Genome-Wide Association Study ; Age of Onset ; *Amyotrophic Lateral Sclerosis/epidemiology/genetics ; Polymorphism, Single Nucleotide/genetics ; Risk Factors ; }, abstract = {OBJECTIVE: Age at onset (AAO) is an essential clinical feature associated with disease progression and mortality in amyotrophic lateral sclerosis (ALS). Identification of genetic variants and environmental risk factors influencing AAO of ALS could help better understand the disease's biological mechanism and provide clinical guidance. However, most genetic studies focused on the risk of ALS, while the genetic background of AAO is less explored. This study aimed to identify genetic and environmental determinants for AAO of ALS.

METHODS: We performed a genome-wide association analysis using a Cox proportional hazards model on AAO of ALS in 10,068 patients. We further conducted colocalization analysis and in-vitro functional exploration for the target variants, as well as Mendelian randomization analysis to identify risk factors influencing AAO of ALS.

RESULTS: The total heritability of AAO of ALS was ~0.16 (standard error [SE] = 0.03). One novel locus rs2046243 (CTIF) was significantly associated with earlier AAO by ~1.29 years (p = 1.68E-08, beta = 0.10, SE = 0.02). Functional exploration suggested this variant was associated with increased expression of CTIF in multiple tissues including the brain. Colocalization analysis detected a colocalization signal at the locus between AAO of ALS and expression of CTIF. Causal inference indicated higher education level was associated with later AAO.

INTERPRETATION: These findings improve the current knowledge of the genetic and environmental etiology of AAO of ALS, and provide a novel target CTIF for further research on ALS pathogenesis and potential therapeutic options to delay the disease onset. ANN NEUROL 2023;94:933-941.}, } @article {pmid37528084, year = {2023}, author = {Gao, XK and Sheng, ZK and Lu, YH and Sun, YT and Rao, XS and Shi, LJ and Cong, XX and Chen, X and Wu, HB and Huang, M and Zheng, Q and Guo, JS and Jiang, LJ and Zheng, LL and Zhou, YT}, title = {VAPB-mediated ER-targeting stabilizes IRS-1 signalosomes to regulate insulin/IGF signaling.}, journal = {Cell discovery}, volume = {9}, number = {1}, pages = {83}, pmid = {37528084}, issn = {2056-5968}, support = {32270720//National Natural Science Foundation of China (National Science Foundation of China)/ ; 91954121//National Natural Science Foundation of China (National Science Foundation of China)/ ; T2121004//National Natural Science Foundation of China (National Science Foundation of China)/ ; 32100671//National Natural Science Foundation of China (National Science Foundation of China)/ ; 82072201//National Natural Science Foundation of China (National Science Foundation of China)/ ; 2021M702848//China Postdoctoral Science Foundation/ ; }, abstract = {The scaffold protein IRS-1 is an essential node in insulin/IGF signaling. It has long been recognized that the stability of IRS-1 is dependent on its endomembrane targeting. However, how IRS-1 targets the intracellular membrane, and what type of intracellular membrane is actually targeted, remains poorly understood. Here, we found that the phase separation-mediated IRS-1 puncta attached to endoplasmic reticulum (ER). VAPB, an ER-anchored protein that mediates tethers between ER and membranes of other organelles, was identified as a direct interacting partner of IRS-1. VAPB mainly binds active IRS-1 because IGF-1 enhanced the VAPB-IRS-1 association and replacing of the nine tyrosine residues of YXXM motifs disrupted the VAPB-IRS-1 association. We further delineated that the Y745 and Y746 residues in the FFAT-like motif of IRS-1 mediated the association with VAPB. Notably, VAPB targeted IRS-1 to the ER and subsequently maintained its stability. Consistently, ablation of VAPB in mice led to downregulation of IRS-1, suppression of insulin signaling, and glucose intolerance. The amyotrophic lateral sclerosis (ALS)-derived VAPB P56S mutant also impaired IRS-1 stability by interfering with the ER-tethering of IRS-1. Our findings thus revealed a previously unappreciated condensate-membrane contact (CMC), by which VAPB stabilizes the membraneless IRS-1 signalosome through targeting it to ER membrane.}, } @article {pmid37527763, year = {2023}, author = {Cao, MC and Ryan, B and Wu, J and Curtis, MA and Faull, RLM and Dragunow, M and Scotter, EL}, title = {A panel of TDP-43-regulated splicing events verifies loss of TDP-43 function in amyotrophic lateral sclerosis brain tissue.}, journal = {Neurobiology of disease}, volume = {185}, number = {}, pages = {106245}, doi = {10.1016/j.nbd.2023.106245}, pmid = {37527763}, issn = {1095-953X}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/metabolism ; Brain/metabolism ; *DNA-Binding Proteins/genetics/metabolism ; *Frontotemporal Dementia/genetics ; RNA ; RNA Splicing ; }, abstract = {TDP-43 dysfunction is a molecular hallmark of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). A major hypothesis of TDP-43 dysfunction in disease is the loss of normal nuclear function, resulting in impaired RNA regulation and the emergence of cryptic exons. Cryptic exons and differential exon usage are emerging as promising markers of lost TDP-43 function in addition to revealing biological pathways involved in neurodegeneration in ALS/FTD. In this brief report, we identified markers of TDP-43 loss of function by depleting TARDBP from post-mortem human brain pericytes, a manipulable in vitro primary human brain cell model, and identifying differential exon usage events with bulk RNA-sequencing analysis. We present these data in an interactive database (https://www.scotterlab.auckland.ac.nz/research-themes/tdp43-lof-db-v2/) together with seven other TDP-43-depletion datasets we meta-analysed previously, for user analysis of differential expression and splicing signatures. Differential exon usage events that were validated by qPCR were then compiled into a 'differential exon usage panel' with other well-established TDP-43 loss-of-function exon markers. This differential exon usage panel was investigated in ALS and control motor cortex tissue to verify whether, and to what extent, TDP-43 loss of function occurs in ALS. We find that profiles of TDP-43-regulated cryptic exons, changed exon usage and changed 3' UTR usage discriminate ALS brain tissue from controls, verifying that TDP-43 loss of function occurs in ALS. We propose that TDP-43-regulated splicing events that occur in brain tissue will have promise as predictors of disease.}, } @article {pmid37527465, year = {2023}, author = {Kahriman, A and Bouley, J and Tuncali, I and Dogan, EO and Pereira, M and Luu, T and Bosco, DA and Jaber, S and Peters, OM and Brown, RH and Henninger, N}, title = {Repeated mild traumatic brain injury triggers pathology in asymptomatic C9ORF72 transgenic mice.}, journal = {Brain : a journal of neurology}, volume = {146}, number = {12}, pages = {5139-5152}, pmid = {37527465}, issn = {1460-2156}, support = {MC_PC_16030/2/MRC_/Medical Research Council/United Kingdom ; R01 NS111990/NS/NINDS NIH HHS/United States ; MR/W004879/1/MRC_/Medical Research Council/United Kingdom ; K08 NS091499/NS/NINDS NIH HHS/United States ; R01 NS104022/NS/NINDS NIH HHS/United States ; R21 NS131756/NS/NINDS NIH HHS/United States ; T32 AI095213/AI/NIAID NIH HHS/United States ; R01 NS088689/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Female ; Male ; Mice ; *Amyotrophic Lateral Sclerosis/genetics ; *Brain Concussion/pathology ; *C9orf72 Protein/genetics/metabolism ; DNA Repeat Expansion ; *Frontotemporal Dementia/genetics/pathology ; Mice, Transgenic ; *Pick Disease of the Brain ; }, abstract = {Frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) are fatal neurodegenerative diseases that represent ends of the spectrum of a single disease. The most common genetic cause of FTD and ALS is a hexanucleotide repeat expansion in the C9orf72 gene. Although epidemiological data suggest that traumatic brain injury (TBI) represents a risk factor for FTD and ALS, its role in exacerbating disease onset and course remains unclear. To explore the interplay between traumatic brain injury and genetic risk in the induction of FTD/ALS pathology we combined a mild repetitive traumatic brain injury paradigm with an established bacterial artificial chromosome transgenic C9orf72 (C9BAC) mouse model without an overt motor phenotype or neurodegeneration. We assessed 8-10 week-old littermate C9BACtg/tg (n = 21), C9BACtg/- (n = 20) and non-transgenic (n = 21) mice of both sexes for the presence of behavioural deficits and cerebral histopathology at 12 months after repetitive TBI. Repetitive TBI did not affect body weight gain, general neurological deficit severity, nor survival over the 12-month observation period and there was no difference in rotarod performance, object recognition, social interaction and acoustic characteristics of ultrasonic vocalizations of C9BAC mice subjected to repetitive TBI versus sham injury. However, we found that repetitive TBI increased the time to the return of the righting reflex, reduced grip force, altered sociability behaviours and attenuated ultrasonic call emissions during social interactions in C9BAC mice. Strikingly, we found that repetitive TBI caused widespread microglial activation and reduced neuronal density that was associated with loss of histological markers of axonal and synaptic integrity as well as profound neuronal transactive response DNA binding protein 43 kDa mislocalization in the cerebral cortex of C9BAC mice at 12 months; this was not observed in non-transgenic repetitive TBI and C9BAC sham mice. Our data indicate that repetitive TBI can be an environmental risk factor that is sufficient to trigger FTD/ALS-associated neuropathology and behavioural deficits, but not paralysis, in mice carrying a C9orf72 hexanucleotide repeat expansion.}, } @article {pmid37527390, year = {2023}, author = {Firnberg, MT and Lerner, EB and Nan, N and Ma, CX and Shah, MI and Mann, NC and Dayan, PS}, title = {National Variation in EMS Response and Antiepileptic Medication Administration for Children with Seizures in the Prehospital Setting.}, journal = {The western journal of emergency medicine}, volume = {24}, number = {4}, pages = {805-813}, pmid = {37527390}, issn = {1936-9018}, mesh = {Male ; Female ; Humans ; Child ; United States/epidemiology ; Anticonvulsants/therapeutic use ; Midazolam/therapeutic use ; *Emergency Medical Services ; *Emergency Medical Technicians ; Seizures/drug therapy ; Retrospective Studies ; }, abstract = {BACKGROUND AND OBJECTIVES: Prehospital Advanced Life Support (ALS) is important to improve patient outcomes in children with seizures, yet data is limited regarding national prehospital variation in ALS response for these children. We aimed to determine the variation in ALS response and prehospital administration of antiepileptic medication for children with seizures across the United States.

METHODS: We analyzed children <19 years with 9-1-1 dispatch codes for seizure in the 2019 National Emergency Medical Services Information System dataset. We defined ALS response as ALS-paramedic, ALS-Advanced Emergency Medical Technician, or ALS-intermediate responses. We conducted regression analyses to identify associations between ALS response (primary outcome), antiepileptic administration (secondary outcome) and age, gender, location, and US census regions.

RESULTS: Of 147,821 pediatric calls for seizures, 88% received ALS responses. Receipt of ALS response was associated with urbanicity, with wilderness (adjusted odds ratio [aOR] 0.44, 0.39-0.49) and rural (aOR 0.80, 0.75-0.84) locations less likely to have ALS responses than urban areas. Of 129,733 emergency medical service (EMS) activations with an ALS responder's impression of seizure, antiepileptic medications were administered in 9%. Medication administration was independently associated with age (aOR 1.008, 95% confidence interval [CI] 1.005-1.010) and gender (aOR 1.22, 95% CI 1.18-1.27), with females receiving medications more than males. Of the 11,698 children who received antiepileptic medications, midazolam was the most commonly used (83%).

CONCLUSION: The majority of children in the US receive ALS responses for seizures. Although medications are infrequently administered, the majority who received medications had midazolam given, which is the current standard of care. Further research should determine the proportion of children who are continuing to seize upon EMS arrival and would most benefit from immediate treatment.}, } @article {pmid37526799, year = {2024}, author = {Brylev, L and Demeshonok, VS and Ataulina, AI and Kovalchuk, MO and Druzhinin, DS and Guekht, AB}, title = {Validity and reliability of the Russian version of the revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R).}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {45}, number = {1}, pages = {187-189}, pmid = {37526799}, issn = {1590-3478}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis ; Reproducibility of Results ; Activities of Daily Living ; Russia ; }, abstract = {OBJECTIVE: The aim of this study is to elaborate a valid and reliable Russian version of the ALSFRS-R.

METHODS: Russian adaptation of the ALSFRS-R was applied twice in 50 ALS patients followed by the test-retest analysis with a 7-day interval between applications and internal consistency analysis.

RESULTS: Test-retest analysis showed very strong correlation for all of the ALSFRS-R variables. The intra-class correlation coefficient was 0.83.

CONCLUSION: The elaborated Russian version of the ALSFRS-R has shown to be comparable with the original English version of the scale.}, } @article {pmid37525592, year = {2023}, author = {Brooks, BR and Pioro, EP and Sakata, T and Takahashi, F and Hagan, M and Apple, S}, title = {The effects of intervention with intravenous edaravone in Study 19 on hospitalization, tracheostomy, ventilation, and death in patients with amyotrophic lateral sclerosis.}, journal = {Muscle & nerve}, volume = {68}, number = {4}, pages = {397-403}, doi = {10.1002/mus.27946}, pmid = {37525592}, issn = {1097-4598}, mesh = {Humans ; Edaravone/therapeutic use ; *Amyotrophic Lateral Sclerosis/drug therapy ; Tracheostomy ; Proportional Hazards Models ; Survival Analysis ; }, abstract = {INTRODUCTION/AIMS: Intravenous (IV) edaravone is a US Food and Drug Administration-approved treatment for amyotrophic lateral sclerosis (ALS), shown in clinical trials to slow physical functional decline. In this study we compared the effect of IV edaravone (edaravone-first group) versus placebo followed by IV edaravone (placebo-first group) on survival and additional milestone events.

METHODS: This work is a post hoc analysis of Study 19/MCI186-19, which was a randomized, placebo-controlled, phase 3 study investigating IV edaravone versus placebo. Study 19 and its 24-week extension have been described previously (NCT01492686). Edaravone-first versus placebo-first group time to events for specific milestone(s) were analyzed post hoc. Time-to-event composite endpoints were time to death; time to death, tracheostomy, or permanent assisted ventilation (PAV); and time to death, tracheostomy, PAV, or hospitalization.

RESULTS: The risk for death, tracheostomy, PAV, or hospitalization was 53% lower among patients in the edaravone-first vs placebo-first groups (hazard ratio = 0.47 [95% confidence interval 0.25 to 0.88], P = .02). The overall effect of IV edaravone on ALS progression could be seen in the significant separation of time-to-event curves for time to death, tracheostomy, PAV, or hospitalization. ALS survival composite endpoint analyses (ALS/SURV) suggested a treatment benefit (least-squares mean difference) for the edaravone-first versus the placebo-first group at week 24 (0.15 ± 0.05 [95% confidence interval 0.06 to 0.25], P < .01) and week 48 (0.11 ± 0.05 [95% confidence interval 0.02 to 0.21], P = .02).

DISCUSSION: These analyses illustrate the value of timely and continued IV edaravone treatment, as earlier initiation was associated with a lower risk of death, tracheostomy, PAV, or hospitalization in patients with ALS.}, } @article {pmid37525497, year = {2024}, author = {Chong, ZZ and Menkes, DL and Souayah, N}, title = {Pathogenesis underlying hexanucleotide repeat expansions in C9orf72 gene in amyotrophic lateral sclerosis.}, journal = {Reviews in the neurosciences}, volume = {35}, number = {1}, pages = {85-97}, pmid = {37525497}, issn = {2191-0200}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/pathology ; C9orf72 Protein/genetics/metabolism ; Proteins/genetics/metabolism ; Dipeptides/genetics/metabolism ; RNA ; Arginine ; Alanine ; Glycine ; Proline ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a rapidly progressive and fatal neurodegenerative disorder. Mutations in C9orf72 and the resulting hexanucleotide repeat (GGGGCC) expansion (HRE) has been identified as a major cause of familial ALS, accounting for about 40 % of familial and 6 % of sporadic cases of ALS in Western patients. The pathological outcomes of HRE expansion in ALS have been recognized as the results of two mechanisms that include both the toxic gain-of-function and loss-of-function of C9ORF72. The gain of toxicity results from RNA and dipeptide repeats (DPRs). The HRE can be bidirectionally transcribed into RNA foci, which can bind to and disrupt RNA splicing, transport, and translation. The DPRs that include poly-glycine-alanine, poly-glycine-proline, poly-glycine- arginine, poly-proline-alanine, and poly-proline-arginine can induce toxicity by direct binding and sequestrating other proteins to interfere rRNA synthesis, ribosome biogenesis, translation, and nucleocytoplasmic transport. The C9ORF72 functions through binding to its partners-Smith-Magenis chromosome regions 8 (SMCR8) and WD repeat-containing protein (WDR41). Loss of C9ORF72 function results in impairment of autophagy, deregulation of autoimmunity, increased stress, and disruption of nucleocytoplasmic transport. Further insight into the mechanism in C9ORF72 HRE pathogenesis will facilitate identifying novel and effective therapeutic targets for ALS.}, } @article {pmid37525032, year = {2023}, author = {Papageorgiou, L and Mangana, E and Papakonstantinou, E and Diakou, I and Pierouli, K and Dragoumani, K and Bacopoulou, F and Chrousos, GP and Exarchos, TP and Vlamos, P and Eliopoulos, E and Vlachakis, D}, title = {An Updated Evolutionary and Structural Study of TBK1 Reveals Highly Conserved Motifs as Potential Pharmacological Targets in Neurodegenerative Diseases.}, journal = {Advances in experimental medicine and biology}, volume = {1423}, number = {}, pages = {41-57}, pmid = {37525032}, issn = {0065-2598}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy/genetics ; Phylogeny ; *Neurodegenerative Diseases/drug therapy/genetics ; Phosphorylation ; NF-kappa B/metabolism ; Protein Serine-Threonine Kinases/genetics/metabolism ; }, abstract = {TANK-binding kinase 1 protein (TBK1) is a kinase that belongs to the IκB (IKK) family. TBK1, also known as T2K, FTDALS4, NAK, IIAE8, and NF-κB, is responsible for the phosphorylation of the amino acid residues, serine and threonine. This enzyme is involved in various key biological processes, including interferon activation and production, homeostasis, cell growth, autophagy, insulin production, and the regulation of TNF-α, IFN-β, and IL-6. Mutations in the TBK1 gene alter the protein's normal function and may lead to an array of pathological conditions, including disorders of the central nervous system. The present study sought to elucidate the role of the TBK1 protein in amyotrophic lateral sclerosis (ALS), a human neurodegenerative disorder. A broad evolutionary and phylogenetic analysis of TBK1 was performed across numerous organisms to distinguish conserved regions important for the protein's function. Subsequently, mutations and SNPs were explored, and their potential effect on the enzyme's function was investigated. These analytical steps, in combination with the study of the secondary, tertiary, and quaternary structure of TBK1, enabled the identification of conserved motifs, which can function as novel pharmacological targets and inform therapeutic strategies for amyotrophic lateral sclerosis.}, } @article {pmid37524961, year = {2023}, author = {Ferraro, PM and Ponzano, M and Cillerai, M and Signori, A and Caponnetto, C}, title = {Reply to "Cognition and motor phenotypes in ALS: a retrospective study".}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {44}, number = {12}, pages = {4531-4533}, pmid = {37524961}, issn = {1590-3478}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics ; Retrospective Studies ; Cognition ; *Motor Cortex ; Phenotype ; }, } @article {pmid37524863, year = {2023}, author = {Verdile, V and Riccioni, V and Guerra, M and Ferrante, G and Sette, C and Valle, C and Ferri, A and Paronetto, MP}, title = {An impaired splicing program underlies differentiation defects in hSOD1[G93A] neural progenitor cells.}, journal = {Cellular and molecular life sciences : CMLS}, volume = {80}, number = {8}, pages = {236}, pmid = {37524863}, issn = {1420-9071}, support = {IG21877//Associazione Italiana per la Ricerca sul Cancro/ ; }, mesh = {Animals ; *Neural Stem Cells/metabolism/cytology ; Mice ; *Cell Differentiation/genetics ; *Amyotrophic Lateral Sclerosis/genetics/pathology/metabolism ; *Neurogenesis/genetics ; Superoxide Dismutase-1/genetics/metabolism ; Motor Neurons/metabolism/pathology ; Disease Models, Animal ; RNA Splicing/genetics ; Humans ; Mice, Transgenic ; Alternative Splicing/genetics ; Cell Proliferation/genetics ; Mutation ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is an adult devastating neurodegenerative disease characterized by the loss of upper and lower motor neurons (MNs), resulting in progressive paralysis and death. Genetic animal models of ALS have highlighted dysregulation of synaptic structure and function as a pathogenic feature of ALS-onset and progression. Alternative pre-mRNA splicing (AS), which allows expansion of the coding power of genomes by generating multiple transcript isoforms from each gene, is widely associated with synapse formation and functional specification. Deciphering the link between aberrant splicing regulation and pathogenic features of ALS could pave the ground for novel therapeutic opportunities. Herein, we found that neural progenitor cells (NPCs) derived from the hSOD1[G93A] mouse model of ALS displayed increased proliferation and propensity to differentiate into neurons. In parallel, hSOD1[G93A] NPCs showed impaired splicing patterns in synaptic genes, which could contribute to the observed phenotype. Remarkably, master splicing regulators of the switch from stemness to neural differentiation are de-regulated in hSOD1[G93A] NPCs, thus impacting the differentiation program. Our data indicate that hSOD1[G93A] mutation impacts on neurogenesis by increasing the NPC pool in the developing mouse cortex and affecting their intrinsic properties, through the establishment of a specific splicing program.}, } @article {pmid37524529, year = {2023}, author = {Kvam, KA and Benatar, M and Brownlee, A and Caller, T and Das, RR and Green, P and Kolodziejczak, S and Russo, J and Sanders, D and Sethi, N and Stavros, K and Stierwalt, J and Giles Walters, N and Bennett, A and Wessels, SR and Brooks, BR}, title = {Amyotrophic Lateral Sclerosis Quality Measurement Set 2022 Update: Quality Improvement in Neurology.}, journal = {Neurology}, volume = {101}, number = {5}, pages = {223-232}, pmid = {37524529}, issn = {1526-632X}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy ; Quality Improvement ; *Neurology ; }, } @article {pmid37524128, year = {2023}, author = {Bernstein, HG and Smalla, KH and Keilhoff, G and Dobrowolny, H and Kreutz, MR and Steiner, J}, title = {The many "Neurofaces" of Prohibitins 1 and 2: Crucial for the healthy brain, dysregulated in numerous brain disorders.}, journal = {Journal of chemical neuroanatomy}, volume = {132}, number = {}, pages = {102321}, doi = {10.1016/j.jchemneu.2023.102321}, pmid = {37524128}, issn = {1873-6300}, mesh = {Humans ; *Prohibitins ; Endothelial Cells/metabolism ; Mitochondria/metabolism ; Brain/metabolism ; *Brain Diseases/metabolism ; }, abstract = {Prohibitin 1 (PHB1) and prohibitin 2 (PHB2) are proteins that are nearly ubiquitously expressed. They are localized in mitochondria, cytosol and cell nuclei. In the healthy CNS, they occur in neurons and non-neuronal cells (oligodendrocytes, astrocytes, microglia, and endothelial cells) and fulfill pivotal functions in brain development and aging, the regulation of brain metabolism, maintenance of structural integrity, synapse formation, aminoacidergic neurotransmission and, probably, regulation of brain action of certain hypothalamic-pituitary hormones.With regard to the diseased brain there is increasing evidence that prohibitins are prominently involved in numerous major diseases of the CNS, which are summarized and discussed in the present review (brain tumors, neurotropic viruses, Alzheimer disease, Down syndrome, Fronto-temporal and vascular dementia, dementia with Lewy bodies, Parkinson disease, Huntington disease, Multiple sclerosis, Amyotrophic lateral sclerosis, stroke, alcohol use disorder, schizophrenia and autism). Unfortunately, there is no PHB-targeted therapy available for any of these diseases.}, } @article {pmid37523555, year = {2023}, author = {Chiot, A and Roemer, SF and Ryner, L and Bogachuk, A and Emberley, K and Brownell, D and Jimenez, GA and Leviten, M and Woltjer, R and Dickson, DW and Steinman, L and Ajami, B}, title = {Elevated α5 integrin expression on myeloid cells in motor areas in amyotrophic lateral sclerosis is a therapeutic target.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {120}, number = {32}, pages = {e2306731120}, pmid = {37523555}, issn = {1091-6490}, support = {P01 NS084974/NS/NINDS NIH HHS/United States ; P30 AG062677/AG/NIA NIH HHS/United States ; U19 AG063911/AG/NIA NIH HHS/United States ; }, mesh = {Mice ; Humans ; Animals ; *Amyotrophic Lateral Sclerosis/metabolism ; Superoxide Dismutase-1/genetics/metabolism ; Integrin alpha5/metabolism ; *Motor Cortex ; Mice, Transgenic ; Superoxide Dismutase/metabolism ; Macrophages/metabolism ; Disease Models, Animal ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal disease affecting upper and lower motor neurons. Microglia directly interact with motor neurons and participate in the progression of ALS. Single-cell mass cytometry (CyTOF) analysis revealed prominent expression of α5 integrin in microglia and macrophages in a superoxide dismutase-1 G93A mouse model of ALS (SOD1[G93A]). In postmortem tissues from ALS patients with various clinical ALS phenotypes and disease duration, α5 integrin is prominent in motor pathways of the central and peripheral nervous system and in perivascular zones associated with the blood-brain barrier. In SOD1[G93A] mice, administration of a monoclonal antibody against α5 integrin increased survival compared to an isotype control and improved motor function on behavioral testing. Together, these findings in mice and in humans suggest that α5 integrin is a potential therapeutic target in ALS.}, } @article {pmid37522762, year = {2023}, author = {Webber, CJ and Murphy, CN and Rondón-Ortiz, AN and van der Spek, SJF and Kelly, EX and Lampl, NM and Chiesa, G and Khalil, AS and Emili, A and Wolozin, B}, title = {Human herpesvirus 8 ORF57 protein is able to reduce TDP-43 pathology: network analysis identifies interacting pathways.}, journal = {Human molecular genetics}, volume = {32}, number = {20}, pages = {2966-2980}, pmid = {37522762}, issn = {1460-2083}, support = {R01 EB029483/EB/NIBIB NIH HHS/United States ; AG080810/NH/NIH HHS/United States ; }, mesh = {Humans ; *Herpesvirus 8, Human/metabolism ; Proteomics ; *Neuroblastoma ; DNA-Binding Proteins/genetics/metabolism ; Cell Line ; *Amyotrophic Lateral Sclerosis/metabolism ; Viral Regulatory and Accessory Proteins/metabolism ; }, abstract = {Aggregation of TAR DNA-binding protein 43 kDa (TDP-43) is thought to drive the pathophysiology of amyotrophic lateral sclerosis and some frontotemporal dementias. TDP-43 is normally a nuclear protein that in neurons translocates to the cytoplasm and can form insoluble aggregates upon activation of the integrated stress response (ISR). Viruses evolved to control the ISR. In the case of Herpesvirus 8, the protein ORF57 acts to bind protein kinase R, inhibit phosphorylation of eIF2α and reduce activation of the ISR. We hypothesized that ORF57 might also possess the ability to inhibit aggregation of TDP-43. ORF57 was expressed in the neuronal SH-SY5Y line and its effects on TDP-43 aggregation characterized. We report that ORF57 inhibits TDP-43 aggregation by 55% and elicits a 2.45-fold increase in the rate of dispersion of existing TDP-43 granules. These changes were associated with a 50% decrease in cell death. Proteomic studies were carried out to identify the protein interaction network of ORF57. We observed that ORF57 directly binds to TDP-43 as well as interacts with many components of the ISR, including elements of the proteostasis machinery known to reduce TDP-43 aggregation. We propose that viral proteins designed to inhibit a chronic ISR can be engineered to remove aggregated proteins and dampen a chronic ISR.}, } @article {pmid37522559, year = {2023}, author = {Kaur, K and Chen, PC and Ko, MW and Huerta-Yepez, S and Maharaj, D and Jewett, A}, title = {The Potential Role of Cytotoxic Immune Effectors in Amyotrophic Lateral Sclerosis (ALS); A Longitudinal Case Study Comparing Patients with Genetically Identical Healthy Twin.}, journal = {Critical reviews in immunology}, volume = {43}, number = {1}, pages = {27-39}, doi = {10.1615/CritRevImmunol.2023047233}, pmid = {37522559}, issn = {1040-8401}, abstract = {Amyotrophic lateral sclerosis (ALS) is an auto-immune neurodegenerative disorder affecting the motor-neurons. The causes of ALS are heterogeneous, and are only partially understood to date. We studied percentage and function of immune cell subsets in particular natural killer (NK) and CD8+ T cells in an ALS patient and compared the results to those obtained from his genetically identical healthy twin in a longitudinal study. We found several basic mechanisms which were potentially involved in the disease induction and progression. Our findings demonstrate that ALS patient's peripheral blood contained higher NK and B cells and, lower T cell percentages compared with the healthy twin brother's peripheral blood. Significantly increased interferon-gamma secretion by anti-CD3/28 monoclonal antibody-treated peripheral blood mononuclear cells, and sorted CD8+ T cells were observed in the ALS patient, suggesting that hyper-responsiveness of T cell compartment could be a potential mechanism of ALS progression. Significant increase in NK cell function due to genetic mutations in ALS associated genes may partly be responsible for the increase expansion and function of CD8+ T cells with effector/memory phenotype, in addition to direct activation and expansion of antigen specific T cells by such mutations. Weekly N-acetyl cysteine infusion to block cell death in patient in addition to a number of other therapies listed in this paper were not effective, and even though the treatments might have extended the patient's life, it was not curative. Therefore, activated CD8+ T and NK cells are likely cells targeting motor neurons in the patient, and strategies should be designed to decrease the aggressive nature of these cells to achieve longer lasting therapeutic benefits.}, } @article {pmid37522558, year = {2023}, author = {Chen, PC and Kaur, K and Ko, MW and Huerta-Yepez, S and Jain, Y and Jewett, A}, title = {Regulation of Cytotoxic Immune Effector Function by AJ3 Probiotic Bacteria in Amyotrophic Lateral Sclerosis (ALS).}, journal = {Critical reviews in immunology}, volume = {43}, number = {1}, pages = {13-26}, doi = {10.1615/CritRevImmunol.2023047231}, pmid = {37522558}, issn = {1040-8401}, mesh = {Humans ; Interleukin-10/pharmacology ; *Amyotrophic Lateral Sclerosis/therapy ; Leukocytes, Mononuclear ; Interleukin-2 ; Cytokines ; Interferon-gamma ; *Antineoplastic Agents/pharmacology ; Antibodies, Monoclonal ; }, abstract = {Our recent studies indicated that amyotrophic lateral sclerosis (ALS) patients suffer from significantly elevated levels of interferon-gamma (IFN-γ) secretion by natural killer (NK) and CD8+ T cells, which may be responsible for the immune-pathologies seen in central nervous system and in peripheral organs of the patients. In order to counter such elevated induction of IFN-γ in patients we designed a treatment strategy to increase anti-inflammatory cytokine interleukin-10 (IL-10) by the use of probiotic strains which significantly increase the levels of IL-10. Therefore, in this paper we demonstrate disease specific functions of Al-Pro (AJ3) formulated for the adjunct treatment of auto-immune diseases including ALS, and compared the function with CA/I-Pro (AJ4) for the treatment of cancer and viral diseases, and NK-CLK (AJ2) for maintenance of immune balance and promotion of disease prevention. The three different formulations of probiotic bacteria have distinct profiles of activation of peripheral blood mononuclear cells (PBMCs), NK, and CD8+ T cells, and their induced activation is different from those mediated by either IL-2 or IL-2 + anti-CD16 monoclonal antibodies (mAbs) or IL-2 + anti-CD3/CD28 mAbs. IL-2 + anti-CD16 mAb activation of PBMCs and NK cells had the highest IFN-γ/IL-10 ratio, whereas IL-2 combination with sAJ4 had the next highest followed by IL-2 + sAJ2 and the lowest was seen with IL-2 + sAJ3. Accordingly, the highest secretion of IFN-γ was seen when the PBMCs and NK cells were treated with IL-2 + sAJ4, intermediate for IL-2 + sAJ2 and the lowest with IL-2 + sAJ3. The levels of IFN-γ induction and the ratio of IFN-γ to IL-10 induced by different probiotic bacteria formulation in the absence of IL-2 treatment remained much lower when compared to those treated in the presence of IL-2. Of note is the difference between NK cells and CD8+ T cells in which synergistic induction of IFN-y by IL-2 + sAJ4 was significantly higher in NK cells than those seen by CD8+ T cells. Based on these results, sAJ3 should be effective in alleviating auto-immunity seen in ALS since it will greatly regulate the levels and function of IFN-γ negatively, decreasing overactivation of cytotoxic immune effectors and prevention of death in motor neurons.}, } @article {pmid37522557, year = {2023}, author = {Kaur, K and Chen, PC and Ko, MW and Mei, A and Huerta-Yepez, S and Maharaj, D and Malarkannan, S and Jewett, A}, title = {Successes and Challenges in Taming the Beast: Cytotoxic Immune Effectors in Amyotrophic Lateral Sclerosis.}, journal = {Critical reviews in immunology}, volume = {43}, number = {1}, pages = {1-11}, doi = {10.1615/CritRevImmunol.2023047235}, pmid = {37522557}, issn = {1040-8401}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/therapy/metabolism ; Motor Neurons/metabolism/pathology ; Superoxide Dismutase-1/genetics/metabolism/pharmacology ; Cytokines/metabolism ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurological disease characterized by the progressive loss of motor neurons in the brain and spinal cord. No effective therapeutic strategies have been established thus far, and therefore there is a significant unmet need for effective therapeutics to arrest the disease and reverse the pathologies induced by it. Although the cause of ALS is not well-defined, it appears to be heterogenous. Currently over 20 genes have been found to be associated with ALS. Family history can only be found in 10% of ALS patients, but in the remaining 90% no association with family history is found. The most common genetic causes are expansion in the C9orf72 gene and mutations in superoxide dismutase 1, TDP-43, and FUS. In our recent study, we also found mutations in TDP43 and FUS in ALS patients. To understand the pathogenesis of the disease, we set ourselves the task of analyzing the phenotype and function of all key immune effectors in ALS patients, comparing them with either a genetically healthy twin or healthy individuals. Our study demonstrated a significant increase in functional activation of NK and CD8+ T cytotoxic immune effectors and release of significant IFN-γ not only by the effector cells but also in the serum of ALS patients. Longitudinal analysis of CD8+ T cell-mediated IFN-γ secretion from ALS patients demonstrated continued and sustained increase in IFN-γ secretion with periods of decrease which coincided with certain treatments; however, the effects were largely short-lived. N-acetyl cysteine (NAC), one of the treatments used, is known to block cell death; however, even though such treatment was able to block most of the proinflammatory cytokines, chemokines, and growth factor release, it was not able to block IFN-γ and TNF-α, the two cytokines we had demonstrated previously to induce differentiation of the cells. In this review, we discuss the contribution of cytotoxic effector cells, especially primary NK cells, supercharged NK cells (sNK), and the contribution of sNK cells in expansion and functional activation of CD8+ T cells to memory/effector T cells in the pathogenesis of ALS. Potential new targeted therapeutic strategies are also discussed.}, } @article {pmid37521204, year = {2023}, author = {Dou, J and Bakulski, K and Guo, K and Hur, J and Zhao, L and Saez-Atienzar, S and Stark, A and Chia, R and García-Redondo, A and Rojas-Garcia, R and Vázquez Costa, JF and Santiago, RF and Bandres-Ciga, S and Gómez-Garre, P and Periñán, MT and Mir, P and Pérez-Tur, J and Cardona, F and Menendez-Gonzalez, M and Riancho, J and Borrego-Hernández, D and Galán-Dávila, L and Ceberio, JI and Pastor, P and Paradas, C and Dols-Icardo, O and , and Traynor, BJ and Feldman, EL and Goutman, SA}, title = {Erratum: Cumulative Genetic Score and C9orf72 Repeat Status Independently Contribute to Amyotrophic Lateral Sclerosis Risk in 2 Case-Control Studies.}, journal = {Neurology. Genetics}, volume = {9}, number = {5}, pages = {e200095}, pmid = {37521204}, issn = {2376-7839}, abstract = {[This corrects the article DOI: 10.1212/NXG.0000000000200079.].}, } @article {pmid37520962, year = {2023}, author = {Souayah, N and Pahwa, A and Jaffry, M and Patel, T and Nasar, A and Chong, ZZ and Sander, HW}, title = {Electrodiagnostic profile of conduction slowing in amyotrophic lateral sclerosis.}, journal = {Heliyon}, volume = {9}, number = {8}, pages = {e18400}, pmid = {37520962}, issn = {2405-8440}, abstract = {OBJECTIVE: Since motor nerve conduction slowing can occur due to loss of large axons, we investigate the conduction slowing profile in amyotrophic lateral sclerosis (ALS) and identify the limits beyond which the diagnosis of exclusive axonal loss is unlikely.

METHODS: First, using linear regression analysis, we established the range of motor conduction slowing in 76 chronic inflammatory demyelinating polyneuropathy (CIDP) patients. Demyelinating range confidence intervals were defined by assessing conduction velocity (CV), distal latency (DML), and F-wave latency (F) in relation to distal compound muscle action potential (CMAP) amplitude of median, ulnar, fibular, and tibial nerves. Results were subsequently validated in 38 additional CIDP patients. Then, the newly established demyelination confidence intervals were used to investigate the profile of conduction slowing in 95 ALS patients.

RESULTS: CV slowing, prolonged DML, and abnormal F were observed in 22.2%, 19.6%, and 47.1% of the studied nerves respectively in ALS patients. When slowing occurred, it affected more than one segment of the motor nerve, suggesting that CMAP amplitude dependent conduction slowing caused by an exclusive loss of large axons is the main mechanism of slowing. No ALS patient had more than 2 nerves with CV slowing in the confidence interval defined by the regression equations or the American Academy of Neurology (AAN) research criteria for CIDP diagnosis.

CONCLUSIONS: The presence of more than two motor nerves with CV slowing in the demyelinating range defined by the regression analysis or AAN criteria in ALS patients suggests the contribution of acquired demyelination or other additional mechanisms exist in the electrodiagnostic profile of ALS.}, } @article {pmid37520009, year = {2023}, author = {Gouveia, D and Correia, J and Cardoso, A and Carvalho, C and Oliveira, AC and Almeida, A and Gamboa, Ó and Ribeiro, L and Branquinho, M and Sousa, A and Lopes, B and Sousa, P and Moreira, A and Coelho, A and Rêma, A and Alvites, R and Ferreira, A and Maurício, AC and Martins, Â}, title = {Intensive neurorehabilitation and allogeneic stem cells transplantation in canine degenerative myelopathy.}, journal = {Frontiers in veterinary science}, volume = {10}, number = {}, pages = {1192744}, pmid = {37520009}, issn = {2297-1769}, abstract = {INTRODUCTION: Degenerative myelopathy (DM) is a neurodegenerative spinal cord disease with upper motor neurons, with progressive and chronic clinical signs, similar to amyotrophic lateral sclerosis (ALS). DM has a complex etiology mainly associated with SOD1 gene mutation and its toxic role, with no specific treatment. Daily intensive rehabilitation showed survival time near 8 months but most animals are euthanized 6-12 months after clinical signs onset.

METHODS: This prospective controlled blinded cohort clinical study aims to evaluate the neural regeneration response ability of DM dogs subjected to an intensive neurorehabilitation protocol with mesenchymal stem cells (MSCs) transplantation. In total, 13 non-ambulatory (OFS 6 or 8) dogs with homozygous genotype DM/DM and diagnosed by exclusion were included. All were allocated to the intensive neurorehabilitation with MSCs protocol (INSCP) group (n = 8) or to the ambulatory rehabilitation protocol (ARP) group (n = 5), which differ in regard to training intensity, modalities frequency, and MSCs transplantation. The INSCP group was hospitalized for 1 month (T0 to T1), followed by MSCs transplantation (T1) and a second month (T2), whereas the ARP group was under ambulatory treatment for the same 2 months.

RESULTS: Survival mean time of total population was 375 days, with 438 days for the INSCP group and 274 for the ARP group, with a marked difference on the Kaplan-Meier survival analysis. When comparing the literature's results, there was also a clear difference in the one-sample t-test (p = 0.013) with an increase in time of approximately 70%. OFS classifications between groups at each time point were significantly different (p = 0.008) by the one-way ANOVA and the independent sample t-test.

DISCUSSION: This INSCP showed to be safe, feasible, and a possibility for a long progression of DM dogs with quality of life and functional improvement. This study should be continued.}, } @article {pmid37519899, year = {2023}, author = {Feng, T and Minevich, G and Liu, P and Qin, HX and Wozniak, G and Pham, J and Pham, K and Korgaonkar, A and Kurnellas, M and Defranoux, NA and Long, H and Mitra, A and Hu, F}, title = {AAV-GRN partially corrects motor deficits and ALS/FTLD-related pathology in Tmem106b[-/-]Grn[-/-] mice.}, journal = {iScience}, volume = {26}, number = {7}, pages = {107247}, pmid = {37519899}, issn = {2589-0042}, support = {R01 NS088448/NS/NINDS NIH HHS/United States ; R01 NS095954/NS/NINDS NIH HHS/United States ; }, abstract = {Loss of function of progranulin (PGRN), encoded by the granulin (GRN) gene, is implicated in several neurodegenerative diseases. Several therapeutics to boost PGRN levels are currently in clinical trials. However, it is difficult to test the efficacy of PGRN-enhancing drugs in mouse models due to the mild phenotypes of Grn[-/-] mice. Recently, mice deficient in both PGRN and TMEM106B were shown to develop severe motor deficits and pathology. Here, we show that intracerebral ventricle injection of PGRN-expressing AAV1/9 viruses partially rescues motor deficits, neuronal loss, glial activation, and lysosomal abnormalities in Tmem106b[-/-]Grn[-/-] mice. Widespread expression of PGRN is detected in both the brain and spinal cord for both AAV subtypes. However, AAV9 but not AAV1-mediated expression of PGRN results in high levels of PGRN in the serum. Together, these data support using the Tmem106b[-/-]Grn[-/-] mouse strain as a robust mouse model to determine the efficacy of PGRN-elevating therapeutics.}, } @article {pmid37519724, year = {2023}, author = {Khosla, R and Bhagat, H and Lal, P and Anand, A}, title = {ALS plasma reduces the viability of NSC34 cells via altering mRNA expression of VEGF: A short report.}, journal = {Heliyon}, volume = {9}, number = {7}, pages = {e18287}, pmid = {37519724}, issn = {2405-8440}, abstract = {INTRODUCTION: Amyotrophic Lateral Sclerosis (ALS) is a devastating neurodegenerative disorder that progressively leads to motor neuron degeneration at the neuromuscular junctions, resulting in paralysis in the patients. The clinical diagnosis of ALS is time taking and further delays the therapeutics that can be helpful if the disease is diagnosed at an early stage. Changes in plasma composition can be reflected upon CSF composition and hence, can be used to study the diagnosis and prognosis markers for the disease.

AIM: To develop a simple model system using motor neuron like cell line after plasma induction.

METHOD: Neuroblastoma × Spinal Cord hybridoma cell line (NSC34) was cultured under appropriate conditions. 10% ALS patients' plasma was added to the media, and cells were conditioned for 12 h. Cell survival analysis and differential gene expression of a panel of molecules (published previously, VEGF, VEGFR2, ANG, OPTN, TDP43, and MCP-1) were done.

RESULTS: ALS patients' plasma impacted the life of the cells and reduced survival to nearly 50% after induction. VEGF was found to be significantly down-regulated in the cells, which can be explained as a reason for reduced cell survival.

CONCLUSION: ALS plasma altered the expression of an essential neuroprotective and growth factor VEGF in NSC34 cells leading to reduced viability.}, } @article {pmid37519256, year = {2023}, author = {Foucher, J and Winroth, I and Lovik, A and Sennfält, S and Pereira, JB and Fang, F and Lule, D and Andersen, PM and Ingre, C}, title = {Validity and reliability measures of the Swedish Karolinska version of the Edinburgh Cognitive and Behavioral ALS Screen (SK-ECAS).}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {}, number = {}, pages = {1-6}, doi = {10.1080/21678421.2023.2239857}, pmid = {37519256}, issn = {2167-9223}, abstract = {OBJECTIVE: Cognitive and behavioral impairment is observed in up to 50% of patients with amyotrophic lateral sclerosis (ALS). The Edinburgh Cognitive and Behavioral ALS Screen (ECAS) is a 5-domain screening tool customized for quick cognitive screening in patients with ALS. Although the ECAS is available in Swedish at the Karolinska University Hospital (SK-ECAS), it has not yet been validated in Sweden stressing the need to assess validity and reliability of the SK-ECAS Version A.

METHODS: The study included 176 patients with ALS or other motor neuron disease diagnosed between September 2017 and October 2021 at the Karolinska ALS Clinical Research Center in Stockholm, Sweden, and 35 age-matched healthy control subjects. SK-ECAS was validated against the Montreal Cognitive Assessment (MoCA) and optimal cutoffs, receiver operating characteristic (ROC) curve and area under the curve (AUC) were calculated.

RESULTS: We identified an optimal cutoff of 108 for the SK-ECAS total score and 82 for the SK-ECAS ALS-specific score to detect cognitive impairment. The SK-ECAS showed good performance in indicating abnormal cognition with an AUC of 0.73 for SK-ECAS ALS-specific score and 0.77 for SK-ECAS total score. There was good internal consistency with a Cronbach's alpha of 0.79.

CONCLUSIONS: This study demonstrates good validity and reliability indices for SK-ECAS Version A for the detection of cognitive impairment in newly diagnosed ALS patients.}, } @article {pmid37519183, year = {2023}, author = {Siokas, V and Liampas, I and Aloizou, AM and Bakirtzis, C and Tsouris, Z and Nousia, A and Nasios, G and Papadimitriou, D and Lavdas, E and Liakos, P and Bogdanos, DP and Hadjigeorgiou, GM and Dardiotis, E}, title = {Lack of Association between CD33 rs3865444 and Amyotrophic Lateral Sclerosis: A Case-Control Study.}, journal = {Journal of integrative neuroscience}, volume = {22}, number = {4}, pages = {106}, doi = {10.31083/j.jin2204106}, pmid = {37519183}, issn = {0219-6352}, support = {5287//Research Committee of the University of Thessaly/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics ; Case-Control Studies ; Sialic Acid Binding Ig-like Lectin 3 ; }, abstract = {BACKGROUND: Microglial activation is considered to assume a role in the pathogenesis of Amyotrophic Lateral Sclerosis (ALS). To date, the relationship between ALS and the rs3865444 polymorphism of the cluster of differentiation 33 (CD33) has not been explored. The current report aimed to investigate the potential connection between CD33 rs3865444 and ALS.

METHODS: Patients diagnosed with sporadic ALS according to the revised El Escorial criteria, as well as age and sex matched community controls, were enrolled. Two evenly numbered, age and sex matched groups of 155 participants each were genotyped.

RESULTS: No association was found between rs3865444 and ALS [log-additive odds ratio (OR) = 0.83 (0.57, 1.22), over-dominant OR = 0.86 (0.55, 1.36), recessive OR = 0.73 (0.25, 2.17), dominant OR = 0.82 (0.52, 1.29), co-dominant OR1 = 0.68 (0.23, 2.05) and co-dominant OR2 = 0.84 (0.53, 1.33)]. Moreover, no relationship was established between rs3865444 and the age of ALS onset based on both unadjusted and sex adjusted Cox-proportional hazards models. Finally, no association between rs3865444 and ALS was found in subgroup analyses based on the site of ALS onset (bulbar or spinal) and sex.

CONCLUSIONS: The current analysis is the first to report that rs3865444 is not linked to ALS. Larger multi-racial studies are required to confirm these findings.}, } @article {pmid37519177, year = {2023}, author = {Blagov, A and Borisov, E and Grechko, A and Popov, M and Sukhorukov, V and Orekhov, A}, title = {The Role of Impaired Mitochondrial Transport in the Development of Neurodegenerative Diseases.}, journal = {Journal of integrative neuroscience}, volume = {22}, number = {4}, pages = {86}, doi = {10.31083/j.jin2204086}, pmid = {37519177}, issn = {0219-6352}, support = {23-25-00237//Russian Science Foundation/ ; }, mesh = {Humans ; *Neurodegenerative Diseases ; Mitochondria ; *Alzheimer Disease ; *Parkinson Disease ; *Huntington Disease ; }, abstract = {The fight against neurodegenerative diseases is one of the key direction of modern medicine. Unfortunately, the difficulties in understanding the factors underlying the development of neurodegeneration hinder the development of breakthrough therapeutics that can stop or at least greatly slow down the progression of these diseases. In this review, it is considered the disruption of mitochondrial transport as one of the pathogenesis factors contributing to neurodegeneration using the examples of Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease. Here, the mechanism of mitochondrial transport under normal conditions and the mechanisms of disturbances for the indicated diseases will be considered.}, } @article {pmid37517821, year = {2023}, author = {Huang, Y and Yang, H and Yang, B and Zheng, Y and Hou, X and Chen, G and Zhang, W and Zeng, X and DU, B}, title = {Ginsenoside-Rg1 combined with a conditioned medium from induced neuron-like hUCMSCs alleviated the apoptosis in a cell model of ALS through regulating the NF-κB/Bcl-2 pathway.}, journal = {Chinese journal of natural medicines}, volume = {21}, number = {7}, pages = {540-550}, doi = {10.1016/S1875-5364(23)60445-5}, pmid = {37517821}, issn = {1875-5364}, mesh = {Humans ; NF-kappa B/genetics/metabolism ; *Ginsenosides/pharmacology ; *Amyotrophic Lateral Sclerosis/drug therapy/genetics ; Culture Media, Conditioned/pharmacology ; Superoxide Dismutase-1 ; *Neurodegenerative Diseases ; Neurons/metabolism ; Apoptosis ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease affecting both upper and lower motor neurons in the brain and spinal cord. One important aspect of ALS pathogenesis is superoxide dismutase 1 (SOD1) mutant-mediated mitochondrial toxicity, leading to apoptosis in neurons. This study aimed to evaluate the neural protective synergistic effects of ginsenosides Rg1 (G-Rg1) and conditioned medium (CM) on a mutational SOD1 cell model, and to explore the underlying mechanisms. We found that the contents of nerve growth factor, glial cell line-derived neurotrophic factor, and brain-derived neurotrophic factor significantly increased in CM after human umbilical cord mesenchymal stem cells (hUCMSCs) were exposed to neuron differentiation reagents for seven days. CM or G-Rg1 decreased the apoptotic rate of SOD1[G93A]-NSC34 cells to a certain extent, but their combination brought about the least apoptosis, compared with CM or G-Rg1 alone. Further research showed that the anti-apoptotic protein Bcl-2 was upregulated in all the treatment groups. Proteins associated with mitochondrial apoptotic pathways, such as Bax, caspase 9 (Cas-9), and cytochrome c (Cyt c), were downregulated. Furthermore, CM or G-Rg1 also inhibited the activation of the nuclear factor-kappa B (NF-κB) signaling pathway by reducing the phosphorylation of p65 and IκBα. CM/G-Rg1 or their combination also reduced the apoptotic rate induced by betulinic acid (BetA), an agonist of the NF-κB signaling pathway. In summary, the combination of CM and G-Rg1 effectively reduced the apoptosis of SOD1[G93A]-NSC34 cells through suppressing the NF-κB/Bcl-2 signaling pathway (Fig. 1 is a graphical representation of the abstract).}, } @article {pmid37517401, year = {2023}, author = {Gerlach, K}, title = {Improvement of Spinocerebellar Ataxia 3 Symptoms Treated with Eurythmy Therapy: A Case Vignette.}, journal = {Complementary medicine research}, volume = {30}, number = {5}, pages = {460-465}, doi = {10.1159/000532120}, pmid = {37517401}, issn = {2504-2106}, mesh = {Male ; Humans ; Middle Aged ; *Machado-Joseph Disease ; *Sleep Wake Disorders ; Ataxia ; Exercise Therapy ; Spasm ; }, abstract = {A 58-year-old male with genetically confirmed spinocerebellar ataxia 3 was treated with 10 sessions of eurythmy therapy. He was rated 9 on the "Scale for Assessment and Rating of Ataxia" before therapy started. Among movement and mental symptoms, he complained about sleep disturbances, insensitivity in the feet, and spasms in the legs. The patient was asked to build strong inner images as a basis for the eurythmy therapy movement exercises. After 10 sessions, he reported improvement in sleep disturbances, insensitivity in the feet, and spasms in the legs. He improved to 7.5 points on the "Scale for Assessment and Rating of Ataxia". In the 3 months, before starting and during eurythmy therapy, the patient did not alter the only medication taken (Bryophyllum 50% powder) and did not undergo any other therapy. Ein 58-jähriger Mann mit genetisch bestätigter spinozerebellärer Ataxie 3 wurde mit 10 Sitzungen Heileurythmie behandelt. Vor Beginn der Therapie wurde er auf der “Scale for Assessment and Rating of Ataxia” mit 9 bewertet. Neben Bewegungs- und psychischen Symptomen klagte er über Schlafstörungen, Unempfindlichkeit in den Füßen und Spasmen in den Beinen. Der Patient wurde aufgefordert, starke innere Bilder als Grundlage für die heileurythmischen Bewegungsübungen aufzubauen. Nach 10 Sitzungen berichtete er über eine Verbesserung der Schlafstörungen, der Unempfindlichkeit in den Füßen und der Spasmen in den Beinen. Er verbesserte sich auf 7.5 Punkte auf der “Scale for Assessment and Rating of Ataxia”. Während der drei Monate vor Beginn und während der Eurythmie Therapie änderte der Patient seine Medikation nicht (Bryophyllum 50% Pulver) und unterzog sich keiner weiteren Therapie.}, } @article {pmid37516990, year = {2023}, author = {Tröger, J and Baltes, J and Baykara, E and Kasper, E and Kring, M and Linz, N and Robin, J and Schäfer, S and Schneider, A and Hermann, A}, title = {PROSA-a multicenter prospective observational study to develop low-burden digital speech biomarkers in ALS and FTD.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {}, number = {}, pages = {1-10}, doi = {10.1080/21678421.2023.2239312}, pmid = {37516990}, issn = {2167-9223}, abstract = {Objective: There is a need for novel biomarkers that can indicate disease state, project disease progression, or assess response to treatment for amyotrophic lateral sclerosis (ALS) and associated neurodegenerative diseases such as frontotemporal dementia (FTD). Digital biomarkers are especially promising as they can be collected non-invasively and at low burden for patients. Speech biomarkers have the potential to objectively measure cognitive, motor as well as respiratory symptoms at low-cost and in a remote fashion using widely available technology such as telephone calls. Methods: The PROSA study aims to develop and evaluate low-burden frequent prognostic digital speech biomarkers. The main goal is to create a single, easy-to-perform battery that serves as a valid and reliable proxy for cognitive, respiratory, and motor domains in ALS and FTD. The study will be a multicenter 12-months observational study aiming to include 75 ALS and 75 FTD patients as well as 50 healthy controls and build on three established longitudinal cohorts: DANCER, DESCRIBE-ALS and DESCRIBE-FTD. In addition to the extensive clinical phenotyping in DESCRIBE, PROSA collects a comprehensive speech protocol in fully remote and automated fashion over the telephone at four time points. This longitudinal speech data, together with gold standard measures, will allow advanced speech analysis using artificial intelligence for the development of speech-based phenotypes of ALS and FTD patients measuring cognitive, motor and respiratory symptoms. Conclusion: Speech-based phenotypes can be used to develop diagnostic and prognostic models predicting clinical change. Results are expected to have implications for future clinical trial stratification as well as supporting innovative trial designs in ALS and FTD.}, } @article {pmid37516812, year = {2023}, author = {Yin, Z and Chen, J and Xia, M and Zhang, X and Li, Y and Chen, Z and Bao, Q and Zhong, W and Yao, J and Wu, K and Zhao, L and Liang, F}, title = {Assessing causal relationship between circulating cytokines and age-related neurodegenerative diseases: a bidirectional two-sample Mendelian randomization analysis.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {12325}, pmid = {37516812}, issn = {2045-2322}, mesh = {Humans ; Cytokines/genetics ; *Neurodegenerative Diseases/genetics ; Mendelian Randomization Analysis ; *Amyotrophic Lateral Sclerosis/genetics ; Fibroblast Growth Factor 2 ; Genome-Wide Association Study ; *Alzheimer Disease ; *Parkinson Disease/genetics ; }, abstract = {Numerous studies have reported that circulating cytokines (CCs) are linked to age-related neurodegenerative diseases (ANDDs); however, there is a lack of systematic investigation for the causal association. A two-sample bidirectional Mendelian Randomisation (MR) method was utilized to evaluate the causal effect. We applied genetic variants correlated with concentrations of CCs from a genome-wide association study meta-analysis (n = 8293) as instrumental variables. Summary data of three major ANDDs [Alzheimer's disease (AD), Parkinson's disease (PD), and Amyotrophic lateral sclerosis (ALS)] were identified from the IEU OpenGWAS platform (n = 627, 266). Inverse-variance weighted method is the main approach to analyse causal effect, and MR results are verified by several sensitivity and pleiotropy analyses. In directional MR, it suggested that several CCs were nominally correlated with the risk of ANDDs, with a causal odds ratio (OR) of Interleukin (IL)-5 of 0.909 for AD; OR of IL-2 of 1.169 for PD; and OR of Beta nerve growth factor of 1.142 for ALS). In reverse MR, there were some suggestively causal effects of ANDDs on CCs (AD on increased Basic fibroblast growth factor and IL-12 and decreased Stem cell growth factor beta; PD on decreased Monokine induced by interferon-gamma; ALS on decreased Basic fibroblast growth factor and IL-17). The findings were stable across sensitivity and pleiotropy analyses. However, after Bonferroni correction, there is no statistically significant association between CCs and ANDDs. Through the genetic epidemiological approach, our study assessed the role and presented possible causal associations between CCs and ANDDs. Further studies are warranted to verify the causal associations.}, } @article {pmid37516663, year = {2023}, author = {Ahmed, M and Spicer, C and Harley, J and Taylor, JP and Hanna, M and Patani, R and Greensmith, L}, title = {Amplifying the Heat Shock Response Ameliorates ALS and FTD Pathology in Mouse and Human Models.}, journal = {Molecular neurobiology}, volume = {60}, number = {12}, pages = {6896-6915}, pmid = {37516663}, issn = {1559-1182}, support = {MR/S006591/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Humans ; Animals ; Mice ; *Amyotrophic Lateral Sclerosis/drug therapy/genetics/metabolism ; *Frontotemporal Dementia/drug therapy/genetics/pathology ; Hydroxylamines/therapeutic use ; Heat-Shock Response ; Mutation/genetics ; }, abstract = {Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are now known as parts of a disease spectrum with common pathological features and genetic causes. However, as both conditions are clinically heterogeneous, patient groups may be phenotypically similar but pathogenically and genetically variable. Despite numerous clinical trials, there remains no effective therapy for these conditions, which, in part, may be due to challenges of therapy development in a heterogeneous patient population. Disruption to protein homeostasis is a key feature of different forms of ALS and FTD. Targeting the endogenous protein chaperone system, the heat shock response (HSR) may, therefore, be a potential therapeutic approach. We conducted a preclinical study of a known pharmacological amplifier of the HSR, called arimoclomol, in mice with a mutation in valosin-containing protein (VCP) which causes both ALS and FTD in patients. We demonstrate that amplification of the HSR ameliorates the ALS/FTD-like phenotype in the spinal cord and brain of mutant VCP mice and prevents neuronal loss, replicating our earlier findings in the SOD1 mouse model of ALS. Moreover, in human cell models, we demonstrate improvements in pathology upon arimoclomol treatment in mutant VCP patient fibroblasts and iPSC-derived motor neurons. Our findings suggest that targeting of the HSR may have therapeutic potential, not only in non-SOD1 ALS, but also for the treatment of FTD.}, } @article {pmid37516410, year = {2023}, author = {Ying, Z and Ye, N and Ma, Q and Chen, F and Li, N and Zhen, X}, title = {Targeted to neuronal organelles for CNS drug development.}, journal = {Advanced drug delivery reviews}, volume = {200}, number = {}, pages = {115025}, doi = {10.1016/j.addr.2023.115025}, pmid = {37516410}, issn = {1872-8294}, mesh = {Humans ; Mitochondria/metabolism/pathology ; *Neurodegenerative Diseases/drug therapy/metabolism ; *Parkinson Disease ; Central Nervous System/metabolism/pathology ; Drug Development ; Central Nervous System Agents/pharmacology ; }, abstract = {Significant evidences indicate that sub-cellular organelle dynamics is critical for both physiological and pathological events and therefore may be attractive drug targets displaying great therapeutic potential. Although the basic biological mechanism underlying the dynamics of intracellular organelles has been extensively studied, relative drug development is still limited. In the present review, we show that due to the development of technical advanced imaging tools, especially live cell imaging methods, intracellular organelle dynamics (including mitochondrial dynamics and membrane contact sites) can be dissected at the molecular level. Based on these identified molecular targets, we review and discuss the potential of drug development to target organelle dynamics, especially mitochondria dynamics and ER-organelle membrane contact dynamics, in the central nervous system for treating human diseases, including neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease and amyotrophic lateral sclerosis.}, } @article {pmid37515753, year = {2023}, author = {Manicardi, A and Scarabel, L and Llenes, JM and Montull, JM and Osuna, MD and Torra Farré, J and Milani, A}, title = {Genetic basis and origin of resistance to acetolactate synthase inhibitors in Amaranthus palmeri from Spain and Italy.}, journal = {Pest management science}, volume = {79}, number = {12}, pages = {4886-4896}, doi = {10.1002/ps.7690}, pmid = {37515753}, issn = {1526-4998}, support = {//Agencia Estatal de Investigación/ ; //European Regional Development Fund/ ; //Horizon 2020 Framework Programme/ ; //Ministerio de Ciencia e Innovación/ ; }, mesh = {*Herbicides/pharmacology ; *Amaranthus/genetics ; *Acetolactate Synthase/genetics ; Herbicide Resistance/genetics ; Spain ; Italy ; }, abstract = {BACKGROUND: Amaranthus palmeri is an aggressive annual weed native to the United States, which has become invasive in some European countries. Populations resistant to acetolactate synthase (ALS) inhibitors have been recorded in Spain and Italy, but the evolutionary origin of the resistance traits remains unknown. Bioassays were conducted to identify cross-resistance to ALS inhibitors and a haplotype-based genetic approach was used to elucidate the origin and distribution of resistance in both countries.

RESULTS: Amaranthus palmeri populations were resistant to thifensulfuron-methyl and imazamox, and the 574-Leu mutant ALS allele was found to be the main cause of resistance among them. In two Spanish populations, 376-Glu and 197-Thr mutant ALS alleles were also found. The haplotype analyses revealed the presence of two and four distinct 574-Leu mutant haplotypes in the Italian and Spanish populations, respectively. None was common to both countries, but some mutant haplotypes were shared between geographically close populations or between populations more than 100 km apart. Wide genetic diversity was found in two very close Spanish populations.

CONCLUSION: ALS-resistant A. palmeri populations were introduced to Italy and Spain from outside Europe. Populations from both countries have different evolutionary histories and originate from independent introduction events. ALS resistance then spread over short and long distances by seed dispersal. The higher number and genetic diversity among mutant haplotypes from the Spanish populations indicated recurrent invasions. The implementation of control tactics to limit seed dispersal and the establishment of A. palmeri is recommended in both countries. © 2023 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.}, } @article {pmid37514344, year = {2023}, author = {Lu, H and Liu, Y and Bu, D and Yang, F and Zhang, Z and Qiang, S}, title = {A Double Mutation in the ALS Gene Confers a High Level of Resistance to Mesosulfuron-Methyl in Shepherd's-Purse.}, journal = {Plants (Basel, Switzerland)}, volume = {12}, number = {14}, pages = {}, pmid = {37514344}, issn = {2223-7747}, support = {32102238//National Natural Science Foundation of China/ ; 2021YFD1700102//National Key R&D Program of China/ ; }, abstract = {Shepherd's-purse (Capsella bursa-pastoris), a globally distributed noxious weed species often found in wheat, has evolved resistance to ALS-inhibiting herbicides mainly due to single mutations in the ALS gene. In the present study, dose-response bioassays showed that a shepherd's-purse population (R), collected from Xinghua, Jiangsu Province, China, had high level of resistance to the ALS-inhibiting herbicide, mesosulfuron-methyl (800-fold), and even much higher resistance levels to other reported ALS-inhibiting herbicides, tribenuron-methyl (1313-fold), bensulfuron-methyl (969-fold) and penoxsulam (613-fold). Sequencing of the open reading frame of the ALS gene revealed a double ALS gene mutation (Pro197-Ser plus Trp574-Leu) conferring the high resistance in the R plants. Docking analysis of the ALS protein and mesosulfuron-methyl predicts that the two amino acid substitutions in the R samples reduces the binding energy to the herbicide by decreasing the hydrogen bonds (H-bonds) and other interactions, thus endowing resistance to ALS-inhibiting herbicides. These results demonstrate that the double ALS mutation confers high resistance levels to ALS-inhibiting herbicides. To our knowledge, this is the first evidence of the double ALS mutation in shepherd's-purse endowing ALS-inhibiting herbicide resistance.}, } @article {pmid37513359, year = {2023}, author = {Pecheu, CN and Tchieda, VK and Tajeu, KY and Jiokeng, SLZ and Lesch, A and Tonle, IK and Ngameni, E and Janiak, C}, title = {Electrochemical Determination of Epinephrine in Pharmaceutical Preparation Using Laponite Clay-Modified Graphene Inkjet-Printed Electrode.}, journal = {Molecules (Basel, Switzerland)}, volume = {28}, number = {14}, pages = {}, pmid = {37513359}, issn = {1420-3049}, mesh = {*Graphite/chemistry ; Carbon/chemistry ; Clay ; Electrochemical Techniques/methods ; Epinephrine/chemistry ; Electrodes ; Pharmaceutical Preparations ; }, abstract = {Epinephrine (EP, also called adrenaline) is a compound belonging to the catecholamine neurotransmitter family. It can cause neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, Huntington's disease and amyotrophic lateral sclerosis. This work describes an amperometric sensor for the electroanalytical detection of EP by using an inkjet-printed graphene electrode (IPGE) that has been chemically modified by a thin layer of a laponite (La) clay mineral. The ion exchange properties and permeability of the chemically modified electrode (denoted La/IPGE) were evaluated using multi-sweep cyclic voltammetry, while its charge transfer resistance was determined by electrochemical impedance spectroscopy. The results showed that La/IPGE exhibited higher sensitivity to EP compared to the bare IPGE. The developed sensor was directly applied for the determination of EP in aqueous solution using differential pulse voltammetry. Under optimized conditions, a linear calibration graph was obtained in the concentration range between 0.8 µM and 10 μM. The anodic peak current of EP was directly proportional to its concentration, leading to detection limits of 0.34 μM and 0.26 μM with bare IPGE and La/IPGE, respectively. The sensor was successfully applied for the determination of EP in pharmaceutical preparations. Recovery rates and the effects of interfering species on the detection of EP were evaluated to highlight the selectivity of the elaborated sensor.}, } @article {pmid37512004, year = {2023}, author = {Hildebrand, A and Schreiber, F and Weber, L and Arndt, P and Garz, C and Petri, S and Prudlo, J and Meuth, SG and Waerzeggers, Y and Henneicke, S and Vielhaber, S and Schreiber, S}, title = {Peripheral Nerve Ultrasound for the Differentiation between ALS, Inflammatory, and Hereditary Polyneuropathies.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {59}, number = {7}, pages = {}, pmid = {37512004}, issn = {1648-9144}, support = {02728/STV//Stiftung für Medizinische Wissenschaft/ ; }, mesh = {Humans ; *Polyradiculoneuropathy, Chronic Inflammatory Demyelinating/diagnostic imaging ; *Amyotrophic Lateral Sclerosis/diagnostic imaging ; Peripheral Nerves/diagnostic imaging ; *Polyneuropathies/diagnostic imaging ; Ultrasonography/methods ; }, abstract = {Background and Objectives: Ultrasound (US) is a non-invasive tool for the in vivo detection of peripheral nerve alterations. Materials and Methods: In this study, we applied nerve US to assist the discrimination between the spectrum of amyotrophic lateral sclerosis (ALS, n = 11), chronic inflammatory demyelinating polyradiculoneuropathy (CIDP, n = 5), and genetically confirmed Charcot-Marie-Tooth disease (CMT, n = 5). All participants and n = 15 controls without neurological diseases underwent high-resolution US of the bilateral tibial nerve. The nerve cross-sectional area (CSA) and nerve microvascular blood flow were compared between the groups and related to cerebrospinal fluid (CSF) measures, clinical symptoms, and nerve conduction studies. The analyses are part of a larger multimodal study on the comparison between US and 7 Tesla (7T) magnetic resonance neurography (MRN). Results: The patients and controls were matched with respect to their demographical data. CMT had the longest disease duration, followed by CIDP and ALS. CSA was related to age, weight, and disease duration. CSA was larger in CMT and CIDP compared to ALS and controls. The blood flow was greatest in CIDP, and higher than in CMT, ALS, and controls. In ALS, greater CSA was correlated with greater CSF total protein and higher albumin quotient. The US measures did not correlate with clinical scores or nerve conduction studies in any of the subgroups. Conclusion: Our results point towards the feasibility of CSA and blood flow to discriminate between ALS, CIDP, and CMT, even in groups of small sample size. In ALS, larger CSA could indicate an inflammatory disease subtype characterized by reduced blood-nerve barrier integrity. Our upcoming analysis will focus on the additive value of 7T MRN in combination with US to disentangle the spectrum between more inflammatory or more degenerative disease variants among the disease groups.}, } @article {pmid37511491, year = {2023}, author = {Antonioni, A and Raho, EM and Lopriore, P and Pace, AP and Latino, RR and Assogna, M and Mancuso, M and Gragnaniello, D and Granieri, E and Pugliatti, M and Di Lorenzo, F and Koch, G}, title = {Frontotemporal Dementia, Where Do We Stand? A Narrative Review.}, journal = {International journal of molecular sciences}, volume = {24}, number = {14}, pages = {}, pmid = {37511491}, issn = {1422-0067}, mesh = {Middle Aged ; Humans ; *Frontotemporal Dementia/diagnosis/therapy/pathology ; *Neurodegenerative Diseases ; *Pick Disease of the Brain ; *Amyotrophic Lateral Sclerosis/pathology ; Temporal Lobe/pathology ; }, abstract = {Frontotemporal dementia (FTD) is a neurodegenerative disease of growing interest, since it accounts for up to 10% of middle-age-onset dementias and entails a social, economic, and emotional burden for the patients and caregivers. It is characterised by a (at least initially) selective degeneration of the frontal and/or temporal lobe, generally leading to behavioural alterations, speech disorders, and psychiatric symptoms. Despite the recent advances, given its extreme heterogeneity, an overview that can bring together all the data currently available is still lacking. Here, we aim to provide a state of the art on the pathogenesis of this disease, starting with established findings and integrating them with more recent ones. In particular, advances in the genetics field will be examined, assessing them in relation to both the clinical manifestations and histopathological findings, as well as considering the link with other diseases, such as amyotrophic lateral sclerosis (ALS). Furthermore, the current diagnostic criteria will be explored, including neuroimaging methods, nuclear medicine investigations, and biomarkers on biological fluids. Of note, the promising information provided by neurophysiological investigations, i.e., electroencephalography and non-invasive brain stimulation techniques, concerning the alterations in brain networks and neurotransmitter systems will be reviewed. Finally, current and experimental therapies will be considered.}, } @article {pmid37511443, year = {2023}, author = {Kittipeerapat, N and Fabian, R and Bernsen, S and Weydt, P and Castro-Gomez, S}, title = {Creatine Kinase MB Isoenzyme Is a Complementary Biomarker in Amyotrophic Lateral Sclerosis.}, journal = {International journal of molecular sciences}, volume = {24}, number = {14}, pages = {}, pmid = {37511443}, issn = {1422-0067}, support = {390873048//Deutsche Forschungsgemeinschaft/ ; 21060//Alzheimer Forschung Initiative/ ; 0001//Alle-Lieben-Schmidt e.V/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis ; Isoenzymes ; *Neurodegenerative Diseases ; Creatine Kinase, MB Form ; Creatine Kinase ; Biomarkers ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is an invariably fatal neurodegenerative disease with limited therapeutic options. There is an urgent need for novel biomarkers to be used as surrogates for new therapeutic trials and disease monitoring. In this study, we sought to systematically study creatine kinase isoenzyme MB (CK-MB) in a real-world cohort of ALS patients, assess the diagnostic performance, and evaluate its association with other laboratory and clinical parameters. We reviewed data from 194 consecutive patients that included 130 ALS patients and 64 disease control patients (primary lateral sclerosis [PLS], benign fasciculations syndrome [BFS], Huntington's disease [HD] and Alzheimer's disease [AD]). CK-MB was elevated in the sera of more than half of all patients with ALS. In patients with spinal-onset ALS, CK-MB levels were significantly higher than in patients with other neurodegenerative diseases. Patients with slower rates of functional decline had a significantly higher baseline CK-MB. Furthermore, CK-MB elevations correlated with cardiac troponin T (cTnT) and with revised ALS Functional Rating Scale (ALSFRS-R) bulbar subcategory. We posit that measuring CK-MB in ALS patients in a complimentary fashion could potentially aid in the diagnostic workup of ALS and help discriminate the disease from some ALS mimics and other neurodegenerative diseases. CK-MB levels also may provide valuable prognostic information regarding disease aggressiveness as well as correlations with specific phenotypic presentations.}, } @article {pmid37511314, year = {2023}, author = {Pfaff, AL and Bubb, VJ and Quinn, JP and Koks, S}, title = {A Genome-Wide Screen for the Exonisation of Reference SINE-VNTR-Alus and Their Expression in CNS Tissues of Individuals with Amyotrophic Lateral Sclerosis.}, journal = {International journal of molecular sciences}, volume = {24}, number = {14}, pages = {}, pmid = {37511314}, issn = {1422-0067}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics ; Minisatellite Repeats ; Short Interspersed Nucleotide Elements ; Alu Elements ; RNA, Messenger/genetics ; }, abstract = {The hominid-specific retrotransposon SINE-VNTR-Alu (SVA) is a composite element that has contributed to the genetic variation between individuals and influenced genomic structure and function. SVAs are involved in modulating gene expression and splicing patterns, altering mRNA levels and sequences, and have been associated with the development of disease. We evaluated the genome-wide effects of SVAs present in the reference genome on transcript sequence and expression in the CNS of individuals with and without the neurodegenerative disorder Amyotrophic Lateral Sclerosis (ALS). This study identified SVAs in the exons of 179 known transcripts, several of which were expressed in a tissue-specific manner, as well as 92 novel exonisation events occurring in the motor cortex. An analysis of 65 reference genome SVAs polymorphic for their presence/absence in the ALS consortium cohort did not identify any elements that were significantly associated with disease status, age at onset, and survival. However, there were transcripts, such as transferrin and HLA-A, that were differentially expressed between those with or without disease, and expression levels were associated with the genotype of proximal SVAs. This study demonstrates the functional consequences of several SVA elements altering mRNA splicing patterns and expression levels in tissues of the CNS.}, } @article {pmid37511056, year = {2023}, author = {Bettendorff, L}, title = {Synthetic Thioesters of Thiamine: Promising Tools for Slowing Progression of Neurodegenerative Diseases.}, journal = {International journal of molecular sciences}, volume = {24}, number = {14}, pages = {}, pmid = {37511056}, issn = {1422-0067}, mesh = {Animals ; Humans ; *Neurodegenerative Diseases/drug therapy ; Thiamine/pharmacology/therapeutic use ; Thiamine Pyrophosphate ; Coenzymes ; }, abstract = {Thiamine (vitamin B1) is essential for the brain. This is attributed to the coenzyme role of thiamine diphosphate (ThDP) in glucose and energy metabolism. The synthetic thiamine prodrug, the thioester benfotiamine (BFT), has been extensively studied and has beneficial effects both in rodent models of neurodegeneration and in human clinical studies. BFT has no known adverse effects and improves cognitive outcomes in patients with mild Alzheimer's disease. In cell culture and animal models, BFT has antioxidant and anti-inflammatory properties that seem to be mediated by a mechanism independent of the coenzyme function of ThDP. Recent in vitro studies show that another thiamine thioester, O,S-dibenzoylthiamine (DBT), is even more efficient than BFT, especially with respect to its anti-inflammatory potency, and is effective at lower concentrations. Thiamine thioesters have pleiotropic properties linked to an increase in circulating thiamine concentrations and possibly in hitherto unidentified open thiazole ring derivatives. The identification of the active neuroprotective metabolites and the clarification of their mechanism of action open extremely promising perspectives in the field of neurodegenerative, neurodevelopmental, and psychiatric conditions. The present review aims to summarize existing data on the neuroprotective effects of thiamine thioesters and give a comprehensive account.}, } @article {pmid37511037, year = {2023}, author = {Xiang, L and Wang, Y and Liu, S and Liu, B and Jin, X and Cao, X}, title = {Targeting Protein Aggregates with Natural Products: An Optional Strategy for Neurodegenerative Diseases.}, journal = {International journal of molecular sciences}, volume = {24}, number = {14}, pages = {}, pmid = {37511037}, issn = {1422-0067}, support = {32000387//National Natural Science Foundation of China/ ; LY23C060001//Zhejiang Provincial Natural Science Foundation/ ; 2021LFR053//Scientific Research Foundation of Zhejiang A&F University/ ; 19 0069//Swedish Cancer Society/ ; VR 2019-03604//Swedish Research Council/ ; }, mesh = {Humans ; *Neurodegenerative Diseases/metabolism ; Protein Aggregates ; *Biological Products/pharmacology/therapeutic use ; *Parkinson Disease ; *Alzheimer Disease ; }, abstract = {Protein aggregation is one of the hallmarks of aging and aging-related diseases, especially for the neurodegenerative diseases (NDs) such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), Amyotrophic lateral sclerosis (ALS), and others. In these diseases, many pathogenic proteins, such as amyloid-β, tau, α-Syn, Htt, and FUS, form aggregates that disrupt the normal physiological function of cells and lead to associated neuronal lesions. Protein aggregates in NDs are widely recognized as one of the important targets for the treatment of these diseases. Natural products, with their diverse biological activities and rich medical history, represent a great treasure trove for the development of therapeutic strategies to combat disease. A number of in vitro and in vivo studies have shown that natural products, by virtue of their complex molecular scaffolds that specifically bind to pathogenic proteins and their aggregates, can inhibit the formation of aggregates, disrupt the structure of aggregates and destabilize them, thereby alleviating conditions associated with NDs. Here, we systematically reviewed studies using natural products to improve disease-related symptoms by reducing or inhibiting the formation of five pathogenic protein aggregates associated with NDs. This information should provide valuable insights into new directions and ideas for the treatment of neurodegenerative diseases.}, } @article {pmid37511010, year = {2023}, author = {Carata, E and Muci, M and Di Giulio, S and Mariano, S and Panzarini, E}, title = {Looking to the Future of the Role of Macrophages and Extracellular Vesicles in Neuroinflammation in ALS.}, journal = {International journal of molecular sciences}, volume = {24}, number = {14}, pages = {}, pmid = {37511010}, issn = {1422-0067}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism ; Neuroinflammatory Diseases ; Macrophages/metabolism ; Inflammation/metabolism ; *Extracellular Vesicles/metabolism ; }, abstract = {Neuroinflammation is a common pathological feature of amyotrophic lateral sclerosis (ALS). Although scientific evidence to date does not allow defining neuroinflammation as an ALS trigger, its role in exacerbating motor neuron (MNs) degeneration and disease progression is attracting research interest. Activated CNS (Central Nervous System) glial cells, proinflammatory peripheral and infiltrated T lymphocytes and monocytes/macrophages, as well as the immunoreactive molecules they release, represent the active players for the role of immune dysregulation enhancing neuroinflammation. The crosstalk between the peripheral and CNS immune cells significantly correlates with the survival of ALS patients since the modification of peripheral macrophages can downregulate inflammation at the periphery along the nerves and in the CNS. As putative vehicles for misfolded protein and inflammatory mediators between cells, extracellular vesicles (EVs) have also drawn particular attention in the field of ALS. Both CNS and peripheral immune cells release EVs, which are able to modulate the behavior of neighboring recipient cells; unfortunately, the mechanisms involved in EVs-mediated communication in neuroinflammation remain unclear. This review aims to synthesize the current literature regarding EV-mediated cell-to-cell communication in the brain under ALS, with a particular point of view on the role of peripheral macrophages in responding to inflammation to understand the biological process and exploit it for ALS management.}, } @article {pmid37510999, year = {2023}, author = {Halder, SK and Milner, R}, title = {Spinal Cord Blood Vessels in Aged Mice Show Greater Levels of Hypoxia-Induced Vascular Disruption and Microglial Activation.}, journal = {International journal of molecular sciences}, volume = {24}, number = {14}, pages = {}, pmid = {37510999}, issn = {1422-0067}, support = {RF1 NS119477/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Mice ; *Amyotrophic Lateral Sclerosis/pathology ; Hypoxia ; Microglia/pathology ; *Spinal Cord/pathology ; *White Matter/pathology ; *Aging/pathology ; }, abstract = {In response to chronic mild hypoxia (CMH, 8% O2), spinal cord blood vessels launch a robust angiogenic response that is associated with transient disruption of the blood-spinal cord barrier (BSCB) which, in turn, triggers a microglial vasculo-protective response. Because hypoxia occurs in many age-related conditions, the goal of this study was to define how aging influences these responses by comparing events in young (8-10 weeks) and aged (20 months) mice. This revealed that aged mice had much greater (3-4-fold) levels of hypoxic-induced BSCB disruption than young mice and that, while the early stage of the angiogenic response in aged mice was no different to young mice, the maturation of newly formed vessels was significantly delayed. Interestingly, microglia in the spinal cords of aged mice were much more activated than young mice, even under normoxic conditions, and this was further enhanced by CMH, though, surprisingly, this resulted in reduced microglial clustering around leaky blood vessels and diminished vasculo-protection. Vascular disruption was associated with loss of myelin in spinal cord white matter (WM) in both young and aged mice. Furthermore, it was notable that the spinal cord of aged mice contained a lower density of Olig2+ oligodendroglial cells even under normoxic conditions and that CMH significantly reduced the density of Olig2+ cells in spinal cord WM of the aged, but not the young, mice. These results demonstrate that spinal cord blood vessels of aged mice are much more vulnerable to the damaging effects of hypoxia than young mice, in part due to the reduced vasculo-protection conferred by chronically activated microglial cells. These observations may have implications for the pathogenesis and/or treatment of spinal cord diseases such as amyotrophic lateral sclerosis (ALS) and suggest that an improvement in microglial function could offer therapeutic potential for treating these age-related conditions.}, } @article {pmid37509677, year = {2023}, author = {Zoccolella, S and Giugno, A and Milella, G and Filardi, M and Introna, A and Fraddosio, A and D'Errico, E and Gnoni, V and Tamburrino, L and Urso, D and Caputo, F and Misceo, S and Logroscino, G}, title = {A Clinical Scale for Rating the Severity of Bulbar Lower Motor Neuron Dysfunction in Amyotrophic Lateral Sclerosis.}, journal = {Biomedicines}, volume = {11}, number = {7}, pages = {}, pmid = {37509677}, issn = {2227-9059}, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is characterized by the progressive loss of upper (UMN) and lower motor neurons (LMN) in four different body regions (bulbar, cervical, thoracic, and lumbosacral). Over the past decades, several clinical scoring systems have been developed to assess the UMN and LMN burden in ALS. However, concerning the bulbar LMN burden, the available scoring systems solely assess the presence/absence of bulbar LMN signs without providing a degree of impairment. Therefore, in this study, we proposed a novel scale to stratify subjects with ALS according to the bulbar LMN involvement and assessed its prognostic value.

METHODS: We developed a four-item scale based on the LMN signs according to the El Escorial criteria. Ten raters, specializing in ALS or neurocognitive disorders, retrospectively applied the scale to the first evaluation of 195 patients with ALS. Cohen's kappa (Cohen's k) and an intra-class correlation coefficient (ICC) were used to assess the inter-rater reliability. The Kaplan-Mayer estimator was used to estimate survival distribution according to the bulbar scale scores.

RESULTS: The raters showed a substantial to excellent agreement with Cohen's k, ranging from 0.834 to 0.975, with an overall ICC of 0.922 (95% CI = 0.906-0.936). The survival distribution was statistically different across the three bulbar scale scores (χ[2](2) = 9.50, p < 0.01).

CONCLUSIONS: Our bulbar LMN scale represents a reliable measure of the bulbar LMN signs in ALS. This easy-to-administer clinical scale could provide unique information in phenotyping and predicting survival in ALS.}, } @article {pmid37509570, year = {2023}, author = {Wang, W and Zhang, L and Cao, W and Xia, K and Huo, J and Huang, T and Fan, D}, title = {Systematic Screening of Associations between Medication Use and Risk of Neurodegenerative Diseases Using a Mendelian Randomization Approach.}, journal = {Biomedicines}, volume = {11}, number = {7}, pages = {}, pmid = {37509570}, issn = {2227-9059}, support = {82101489, 81873784, 82071426//National Natural Science Foundation of China/ ; 2021M690255//China Postdoctoral Science Foundation/ ; BYESS2023317//Young Elite Scientists Sponsorship Program by BAST/ ; BYSYDL2019002//Clinical Cohort Construction Program of Peking University Third Hospital/ ; }, abstract = {BACKGROUND: Systematically assessing the causal associations between medications and neurodegenerative diseases is significant in identifying disease etiology and novel therapies. Here, we investigated the putative causal associations between 23 existing medication categories and major neurodegenerative diseases (NDs), including Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS).

METHODS: A two-sample mendelian randomization (MR) approach was conducted. Estimates were calculated using the inverse-variance weighted (IVW) method as the main model. A sensitivity analysis and a pleiotropy analysis were performed to identify potential violations.

RESULTS: Genetically predisposition to antihypertensives (OR = 0.809, 95% CI = 0.668-0.981, p = 0.031), thyroid preparations (OR = 0.948, 95% CI = 0.909-0.988, p = 0.011), and immunosuppressants (OR = 0.879, 95% CI = 0.789-0.979, p = 0.018) was associated with a decreased risk of AD. Genetic proxies for thyroid preparations (OR = 0.934, 95% CI = 0.884-0.988, p = 0.017), immunosuppressants (OR = 0.825, 95% CI = 0.699-0.973, p = 0.022), and glucocorticoids (OR = 0.862, 95% CI = 0.756-0.983, p = 0.027) were causally associated with a decreased risk of PD. Genetically determined antithrombotic agents (OR = 1.234, 95% CI = 1.042-1.461, p = 0.015), HMG CoA reductase inhibitors (OR = 1.085, 95% CI = 1.025-1.148, p = 0.005), and salicylic acid and derivatives (OR = 1.294, 95% CI = 1.078-1.553, p = 0.006) were associated with an increased risk of ALS.

CONCLUSIONS: We presented a systematic view concerning the causal associations between medications and NDs, which will promote the etiology discovery, drug repositioning and patient management for NDs.}, } @article {pmid37509427, year = {2023}, author = {Badini, S and Regondi, S and Lammi, C and Bollati, C and Donvito, G and Pugliese, R}, title = {Computational Mechanics of Form-Fitting 3D-Printed Lattice-Based Wrist-Hand Orthosis for Motor Neuron Disease.}, journal = {Biomedicines}, volume = {11}, number = {7}, pages = {}, pmid = {37509427}, issn = {2227-9059}, support = {F45C22000230003//Regione Lombardia and Unioncamere Lombardia/ ; }, abstract = {Motor neuron disease (MND) patients often experience hand-wrist muscle atrophy resulting in severe social consequences and hampering their daily activities. Although hand-wrist orthosis is commonly used to assist weakened muscles, its effectiveness is limited due to the rapid progression of the disease and the need for customization to suit individual patient requirements. To address these challenges, this study investigates the application of three-dimensional (3D) printing technology to design and fabricate two lattice structures inspired by silkworm cocoons, using poly-ε-caprolactone as feedstock material. Finite element method (FEM) analysis is employed to study the mechanical behavior, enabling control over the geometric configuration incorporated into the hand-wrist orthosis. Through tensile displacement and three-point bending simulations, the stress distribution is examined for both lattice geometries. Geometry-1 demonstrates anisotropic behavior, while geometry-2 exhibits no strict directional dependence due to its symmetry and uniform node positioning. Moreover, the biocompatibility of lattices with human skin fibroblasts is investigated, confirming excellent biocompatibility. Lastly, the study involves semi-structured interviews with MND patients to gather feedback and develop prototypes of form-fitting 3D-printed lattice-based hand-wrist orthosis. By utilizing 3D printing technology, this study aims to provide customized orthosis that can effectively support weakened muscles and reposition the hand for individuals with MND.}, } @article {pmid37509182, year = {2023}, author = {Stump, AL and Rioux, DJ and Albright, R and Melki, GL and Prosser, DC}, title = {Yeast Models of Amyotrophic Lateral Sclerosis Type 8 Mimic Phenotypes Seen in Mammalian Cells Expressing Mutant VAPB[P56S].}, journal = {Biomolecules}, volume = {13}, number = {7}, pages = {}, pmid = {37509182}, issn = {2218-273X}, mesh = {Animals ; Humans ; *Amyotrophic Lateral Sclerosis/metabolism ; Saccharomyces cerevisiae/genetics/metabolism ; Vesicular Transport Proteins/genetics/metabolism ; *Neurodegenerative Diseases ; Mutation ; Mammals/metabolism ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a complex neurodegenerative disease that results in the loss of motor neurons and can occur sporadically or due to genetic mutations. Among the 30 genes linked to familial ALS, a P56S mutation in VAPB, an ER-resident protein that functions at membrane contact sites, causes ALS type 8. Mammalian cells expressing VAPB[P56S] have distinctive phenotypes, including ER collapse, protein and/or membrane-containing inclusions, and sensitivity to ER stress. VAPB is conserved through evolution and has two homologs in budding yeast, SCS2 and SCS22. Previously, a humanized version of SCS2 bearing disease-linked mutations was described, and it caused Scs2-containing inclusions when overexpressed in yeast. Here, we describe a yeast model for ALS8 in which the two SCS genes are deleted and replaced with a single chromosomal copy of either wild-type or mutant yeast SCS2 or human VAPB expressed from the SCS2 promoter. These cells display ER collapse, the formation of inclusion-like structures, and sensitivity to tunicamycin, an ER stress-inducing drug. Based on the phenotypic similarity to mammalian cells expressing VAPB[P56S], we propose that these models can be used to study the molecular basis of cell death or dysfunction in ALS8. Moreover, other conserved ALS-linked genes may create opportunities for the generation of yeast models of disease.}, } @article {pmid37508574, year = {2023}, author = {Malhotra, S and Miras, MCM and Pappolla, A and Montalban, X and Comabella, M}, title = {Liquid Biopsy in Neurological Diseases.}, journal = {Cells}, volume = {12}, number = {14}, pages = {}, pmid = {37508574}, issn = {2073-4409}, mesh = {Humans ; Liquid Biopsy/methods ; *Cell-Free Nucleic Acids ; *MicroRNAs ; *Central Nervous System Neoplasms ; Biomarkers ; }, abstract = {The most recent and non-invasive approach for studying early-stage biomarkers is liquid biopsy. This implies the extraction and analysis of non-solid biological tissues (serum, plasma, saliva, urine, and cerebrospinal fluid) without undergoing invasive procedures to determine disease prognosis. Liquid biopsy can be used for the screening of several components, such as extracellular vesicles, microRNAs, cell-free DNA, cell-free mitochondrial and nuclear DNA, circulating tumour cells, circulating tumour DNA, transfer RNA, and circular DNA or RNA derived from body fluids. Its application includes early disease diagnosis, the surveillance of disease activity, and treatment response monitoring, with growing evidence for validating this methodology in cancer, liver disease, and central nervous system (CNS) disorders. This review will provide an overview of mentioned liquid biopsy components, which could serve as valuable biomarkers for the evaluation of complex neurological conditions, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis, epilepsy, stroke, traumatic brain injury, CNS tumours, and neuroinfectious diseases. Furthermore, this review highlights the future directions and potential limitations associated with liquid biopsy.}, } @article {pmid37508558, year = {2023}, author = {Wu, LY and Song, YJ and Zhang, CL and Liu, J}, title = {KV Channel-Interacting Proteins in the Neurological and Cardiovascular Systems: An Updated Review.}, journal = {Cells}, volume = {12}, number = {14}, pages = {}, pmid = {37508558}, issn = {2073-4409}, mesh = {*Neurons/metabolism ; Carrier Proteins/metabolism ; Kv Channel-Interacting Proteins/genetics/metabolism ; Cell Membrane/metabolism ; *Cardiovascular System/metabolism ; }, abstract = {KV channel-interacting proteins (KChIP1-4) belong to a family of Ca[2+]-binding EF-hand proteins that are able to bind to the N-terminus of the KV4 channel α-subunits. KChIPs are predominantly expressed in the brain and heart, where they contribute to the maintenance of the excitability of neurons and cardiomyocytes by modulating the fast inactivating-KV4 currents. As the auxiliary subunit, KChIPs are critically involved in regulating the surface protein expression and gating properties of KV4 channels. Mechanistically, KChIP1, KChIP2, and KChIP3 promote the translocation of KV4 channels to the cell membrane, accelerate voltage-dependent activation, and slow the recovery rate of inactivation, which increases KV4 currents. By contrast, KChIP4 suppresses KV4 trafficking and eliminates the fast inactivation of KV4 currents. In the heart, IKs, ICa,L, and INa can also be regulated by KChIPs. ICa,L and INa are positively regulated by KChIP2, whereas IKs is negatively regulated by KChIP2. Interestingly, KChIP3 is also known as downstream regulatory element antagonist modulator (DREAM) because it can bind directly to the downstream regulatory element (DRE) on the promoters of target genes that are implicated in the regulation of pain, memory, endocrine, immune, and inflammatory reactions. In addition, all the KChIPs can act as transcription factors to repress the expression of genes involved in circadian regulation. Altered expression of KChIPs has been implicated in the pathogenesis of several neurological and cardiovascular diseases. For example, KChIP2 is decreased in failing hearts, while loss of KChIP2 leads to increased susceptibility to arrhythmias. KChIP3 is increased in Alzheimer's disease and amyotrophic lateral sclerosis, but decreased in epilepsy and Huntington's disease. In the present review, we summarize the progress of recent studies regarding the structural properties, physiological functions, and pathological roles of KChIPs in both health and disease. We also summarize the small-molecule compounds that regulate the function of KChIPs. This review will provide an overview and update of the regulatory mechanism of the KChIP family and the progress of targeted drug research as a reference for researchers in related fields.}, } @article {pmid37508548, year = {2023}, author = {Morello, G and La Cognata, V and Guarnaccia, M and La Bella, V and Conforti, FL and Cavallaro, S}, title = {A Diagnostic Gene-Expression Signature in Fibroblasts of Amyotrophic Lateral Sclerosis.}, journal = {Cells}, volume = {12}, number = {14}, pages = {}, pmid = {37508548}, issn = {2073-4409}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/genetics/metabolism ; Transcriptome/genetics ; *Neurodegenerative Diseases/metabolism ; Gene Expression Profiling/methods ; Fibroblasts/metabolism ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal, progressive neurodegenerative disease with limited treatment options. Diagnosis can be difficult due to the heterogeneity and non-specific nature of the initial symptoms, resulting in delays that compromise prompt access to effective therapeutic strategies. Transcriptome profiling of patient-derived peripheral cells represents a valuable benchmark in overcoming such challenges, providing the opportunity to identify molecular diagnostic signatures. In this study, we characterized transcriptome changes in skin fibroblasts of sporadic ALS patients (sALS) and controls and evaluated their utility as a molecular classifier for ALS diagnosis. Our analysis identified 277 differentially expressed transcripts predominantly involved in transcriptional regulation, synaptic transmission, and the inflammatory response. A support vector machine classifier based on this 277-gene signature was developed to discriminate patients with sALS from controls, showing significant predictive power in both the discovery dataset and in six independent publicly available gene expression datasets obtained from different sALS tissue/cell samples. Taken together, our findings support the utility of transcriptional signatures in peripheral cells as valuable biomarkers for the diagnosis of ALS.}, } @article {pmid37508478, year = {2023}, author = {La Cognata, V and D'Amico, AG and Maugeri, G and Morello, G and Guarnaccia, M and Magrì, B and Aronica, E and D'Agata, V and Cavallaro, S}, title = {CXCR2 Is Deregulated in ALS Spinal Cord and Its Activation Triggers Apoptosis in Motor Neuron-Like Cells Overexpressing hSOD1-G93A.}, journal = {Cells}, volume = {12}, number = {14}, pages = {}, pmid = {37508478}, issn = {2073-4409}, mesh = {Animals ; Humans ; Mice ; *Amyotrophic Lateral Sclerosis/genetics/metabolism ; Apoptosis ; Chemokine CXCL2/metabolism ; Ligands ; Mice, Transgenic ; Motor Neurons/pathology ; *Neurodegenerative Diseases/genetics/metabolism ; Superoxide Dismutase/genetics/metabolism ; Superoxide Dismutase-1/genetics/metabolism ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a multifactorial neurodegenerative disease characterized by progressive depletion of motor neurons (MNs). Recent evidence suggests a role in ALS pathology for the C-X-C motif chemokine receptor 2 (CXCR2), whose expression was found increased at both mRNA and protein level in cortical neurons of sporadic ALS patients. Previous findings also showed that the receptor inhibition is able to prevent iPSC-derived MNs degeneration in vitro and improve neuromuscular function in SOD1-G93A mice. Here, by performing transcriptional analysis and immunofluorescence studies, we detailed the increased expression and localization of CXCR2 and its main ligand CXCL8 in the human lumbar spinal cord of sporadic ALS patients. We further investigated the functional role of CXCR2/ligands axis in NSC-34 motor neuron-like cells expressing human wild-type (WT) or mutant (G93A) SOD1. A significant expression of CXCR2 was found in doxycycline-induced G93A-SOD1-expressing cells, but not in WT cells. In vitro assays showed CXCR2 activation by GROα and MIP2α, two murine endogenous ligands and functional homologs of CXCL8, reduces cellular viability and triggers apoptosis in a dose dependent manner, while treatment with reparixin, a non-competitive allosteric CXCR2 inhibitor, effectively counteracts GROα and MIP2α toxicity, significantly inhibiting the chemokine-induced cell death. Altogether, data further support a role of CXCR2 axis in ALS etiopathogenesis and confirm its pharmacological modulation as a candidate therapeutic strategy.}, } @article {pmid37507754, year = {2023}, author = {Brockmann, SJ and Buck, E and Casoli, T and Meirelles, JL and Ruf, WP and Fabbietti, P and Holzmann, K and Weishaupt, JH and Ludolph, AC and Conti, F and Danzer, KM}, title = {Mitochondrial genome study in blood of maternally inherited ALS cases.}, journal = {Human genomics}, volume = {17}, number = {1}, pages = {70}, pmid = {37507754}, issn = {1479-7364}, mesh = {Humans ; *Genome, Mitochondrial/genetics ; Maternal Inheritance/genetics ; *Amyotrophic Lateral Sclerosis/genetics ; DNA, Mitochondrial/genetics ; Mitochondria/genetics ; Mutation ; }, abstract = {BACKGROUND: ALS is a heterogeneous disease in which different factors such as mitochondrial phenotypes act in combination with a genetic predisposition. This study addresses the question of whether homoplasmic (total mitochondrial genome of a sample is affected) and/or heteroplasmic mutations (wildtype and mutant mitochondrial DNA molecules coexist) might play a role in familial ALS. Blood was drawn from familial ALS patients with a possible maternal pattern of inheritance according to their pedigrees, which was compared to blood of ALS patients without maternal association as well as age-matched controls. In two cohorts, we analyzed the mitochondrial genome from whole blood or isolated white blood cells and platelets using a resequencing microarray (Affymetrix MitoChip v2.0) that is able to detect homoplasmic and heteroplasmic mitochondrial DNA mutations and allows the assessment of low-level heteroplasmy.

RESULTS: We identified an increase in homoplasmic ND5 mutations, a subunit of respiratory chain complex I, in whole blood of ALS patients that allowed maternal inheritance. This effect was more pronounced in patients with bulbar onset. Heteroplasmic mutations were significantly increased in different mitochondrial genes in platelets of patients with possible maternal inheritance. No increase of low-level heteroplasmy was found in maternal ALS patients.

CONCLUSION: Our results indicate a contribution of homoplasmic ND5 mutations to maternally associated ALS with bulbar onset. Therefore, it might be conceivable that specific maternally transmitted rather than randomly acquired mitochondrial DNA mutations might contribute to the disease process. This stands in contrast with observations from Alzheimer's and Parkinson's diseases showing an age-dependent accumulation of unspecific mutations in mitochondrial DNA.}, } @article {pmid37507019, year = {2023}, author = {Clark, NE and Katolik, A and Gallant, P and Welch, A and Murphy, E and Buerer, L and Schorl, C and Naik, N and Naik, MT and Holloway, SP and Cano, K and Weintraub, ST and Howard, KM and Hart, PJ and Jogl, G and Damha, MJ and Fairbrother, WG}, title = {Activation of human RNA lariat debranching enzyme Dbr1 by binding protein TTDN1 occurs though an intrinsically disordered C-terminal domain.}, journal = {The Journal of biological chemistry}, volume = {299}, number = {9}, pages = {105100}, pmid = {37507019}, issn = {1083-351X}, support = {R01 GM094157/GM/NIGMS NIH HHS/United States ; R01 GM095612/GM/NIGMS NIH HHS/United States ; R01 GM105681/GM/NIGMS NIH HHS/United States ; R01 GM127472/GM/NIGMS NIH HHS/United States ; }, mesh = {Humans ; Introns ; *RNA Nucleotidyltransferases/genetics/metabolism ; RNA Splicing ; *Adaptor Proteins, Signal Transducing/metabolism ; Enzyme Activation/genetics ; Protein Domains ; Protein Binding ; Intrinsically Disordered Proteins/genetics/metabolism ; Entamoeba histolytica/enzymology/genetics ; Metals, Heavy/metabolism ; }, abstract = {In eukaryotic cells, the introns are excised from pre-mRNA by the spliceosome. These introns typically have a lariat configuration due to the 2'-5' phosphodiester bond between an internal branched residue and the 5' terminus of the RNA. The only enzyme known to selectively hydrolyze the 2'-5' linkage of these lariats is the RNA lariat debranching enzyme Dbr1. In humans, Dbr1 is involved in processes such as class-switch recombination of immunoglobulin genes, and its dysfunction is implicated in viral encephalitis, HIV, ALS, and cancer. However, mechanistic details of precisely how Dbr1 affects these processes are missing. Here we show that human Dbr1 contains a disordered C-terminal domain through sequence analysis and nuclear magnetic resonance. This domain stabilizes Dbr1 in vitro by reducing aggregation but is dispensable for debranching activity. We establish that Dbr1 requires Fe[2+] for efficient catalysis and demonstrate that the noncatalytic protein Drn1 and the uncharacterized protein trichothiodystrophy nonphotosensitive 1 directly bind to Dbr1. We demonstrate addition of trichothiodystrophy nonphotosensitive 1 to in vitro debranching reactions increases the catalytic efficiency of human Dbr1 19-fold but has no effect on the activity of Dbr1 from the amoeba Entamoeba histolytica, which lacks a disordered C-terminal domain. Finally, we systematically examine how the identity of the branchpoint nucleotide affects debranching rates. These findings describe new aspects of Dbr1 function in humans and further clarify how Dbr1 contributes to human health and disease.}, } @article {pmid37505455, year = {2023}, author = {Dos Santos, MM and Ishida, K}, title = {We need to talk about Candida tropicalis: Virulence factors and survival mechanisms.}, journal = {Medical mycology}, volume = {61}, number = {8}, pages = {}, doi = {10.1093/mmy/myad075}, pmid = {37505455}, issn = {1460-2709}, support = {2022/08516-5//Fundação de Amparo à Pesquisa do Estado de São Paulo/ ; 001 - 88887.663125/2022-00//Coordenação de Aperfeiçoamento de Pessoal de Nível Superior/ ; 306041/2022-7//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; }, mesh = {Animals ; *Candida tropicalis/genetics ; *Antifungal Agents/therapeutic use ; Virulence Factors/genetics/metabolism ; Candida ; Candida albicans ; Drug Resistance, Fungal ; Microbial Sensitivity Tests/veterinary ; }, abstract = {Candida tropicalis is a notable species of the Candida genus representing an impressive epidemiology in tropical regions, especially in South America and Asia, where India already presents the species as the first in Candida epidemiology. Candida tropicalis has also shown a worrying antifungal resistance profile in recent years. It is essential to highlight that each pathogenic species of the Candida genus has a particular biology; however, Candida virulence factors are almost entirely based on studies with C. albicans. The intrinsic resistance of C. krusei to some azoles, the intrinsic osmotolerance of C. tropicalis, and the multidrug resistance of C. auris are just a few examples of how the biology of each Candida species is unique. Despite being a phylogenetically close species, C. tropicalis can support 15% NaCl, antagonistically metabolize and signal N-acetylglucosamine, encode 16 reported ALS genes, and other specificities discussed here compared to C. albicans. It is essential to clarify the details of the C. tropicalis infectious process, including identifying the participating secreted enzyme(s), the factors responsible for tissue damage, and the mechanisms underlying the morphogenesis and tolerance signaling pathways. In this review, we thoroughly assembled what is known about the main virulence factors of C. tropicalis, highlighting the missing pieces to stimulate further research with C. tropicalis and other non-Candida albicans species.}, } @article {pmid37503230, year = {2023}, author = {Broce, IJ and Sirkis, DW and Nillo, RM and Bonham, LW and Lee, SE and Miller, B and Castruita, P and Sturm, VE and Sugrue, LS and Desikan, RS and Yokoyama, JS}, title = {C9orf72 gene networks in the human brain correlate with cortical thickness in C9-FTD and implicate vulnerable cell types.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {37503230}, issn = {2692-8205}, support = {R01 AG062588/AG/NIA NIH HHS/United States ; R01 AG052496/AG/NIA NIH HHS/United States ; T32 AG058529/AG/NIA NIH HHS/United States ; R25 NS117367/NS/NINDS NIH HHS/United States ; R01 AG058233/AG/NIA NIH HHS/United States ; K01 AG070376/AG/NIA NIH HHS/United States ; }, abstract = {INTRODUCTION: A hexanucleotide repeat expansion (HRE) intronic to chromosome 9 open reading frame 72 (C9orf72) is recognized as the most common genetic cause of amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and ALS-FTD. Identifying genes that show similar regional co-expression patterns to C9orf72 may help identify novel gene targets and biological mechanisms that mediate selective vulnerability to ALS and FTD pathogenesis.

METHODS: We leveraged mRNA expression data in healthy brain from the Allen Human Brain Atlas to evaluate C9orf72 co-expression patterns. To do this, we correlated average C9orf72 expression values in 51 regions across different anatomical divisions (cortex, subcortex, cerebellum) with average gene expression values for 15,633 protein-coding genes, including 50 genes known to be associated with ALS, FTD, or ALS-FTD. We then evaluated whether the identified C9orf72 co-expressed genes correlated with patterns of cortical thickness in symptomatic C9orf72 pathogenic HRE carriers (n=19). Lastly, we explored whether genes with significant C9orf72 radiogenomic correlations (i.e., 'C9orf72 gene network') were enriched in specific cell populations in the brain and enriched for specific biological and molecular pathways.

RESULTS: A total of 1,748 genes showed an anatomical distribution of gene expression in the brain similar to C9orf72 and significantly correlated with patterns of cortical thickness in C9orf72 HRE carriers. This C9orf72 gene network was differentially expressed in cell populations previously implicated in ALS and FTD, including layer 5b cells, cholinergic motor neurons in the spinal cord, and medium spiny neurons of the striatum, and was enriched for biological and molecular pathways associated with multiple neurotransmitter systems, protein ubiquitination, autophagy, and MAPK signaling, among others.

CONCLUSIONS: Considered together, we identified a network of C9orf72-associated genes that may influence selective regional and cell-type-specific vulnerabilities in ALS/FTD.}, } @article {pmid37503131, year = {2023}, author = {Hobson, R and Levy, SHS and Flaherty, D and Xiao, H and Ciener, B and Reddy, H and Singal, C and Teich, AF and Shneider, NA and Bradshaw, EM and Elyaman, W}, title = {Clonal CD8 T cells in the leptomeninges are locally controlled and influence microglia in human neurodegeneration.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2023.07.13.548931}, pmid = {37503131}, issn = {2692-8205}, support = {R01 AG067581/AG/NIA NIH HHS/United States ; }, abstract = {Recent murine studies have highlighted a crucial role for the meninges in surveilling the central nervous system (CNS) and influencing CNS inflammation. However, how meningeal immunity is altered in human neurodegeneration and its potential effects on neuroinflammation is understudied. In the present study, we performed single-cell analysis of the transcriptomes and T cell receptor repertoire of 72,576 immune cells from 36 postmortem human brain and leptomeninges tissues from donors with neurodegenerative diseases including amyotrophic lateral sclerosis, Alzheimer's disease, and Parkinson's disease. We identified the meninges as an important site of antigen presentation and CD8 T cell activation and clonal expansion and found that T cell activation in the meninges is a requirement for infiltration into the CNS. We further found that natural killer cells have the potential to negatively regulate T cell activation locally in the meninges through direct killing and are one of many regulatory mechanisms that work to control excessive neuroinflammation.}, } @article {pmid37502965, year = {2023}, author = {Kodavati, M and Wang, H and Guo, W and Mitra, J and Hegde, PM and Provasek, V and Maloji Rao, VH and Vedula, I and Zhang, A and Mitra, S and Tomkinson, AE and Hamilton, DJ and Bosch, LVD and Hegde, ML}, title = {FUS Unveiled in Mitochondrial DNA Repair and Targeted Ligase-1 Expression Rescues Repair-Defects in FUS-Linked Neurodegeneration.}, journal = {Research square}, volume = {}, number = {}, pages = {}, pmid = {37502965}, issn = {2693-5015}, support = {R01 NS094535/NS/NINDS NIH HHS/United States ; R01 ES012512/ES/NIEHS NIH HHS/United States ; R01 NS088645/NS/NINDS NIH HHS/United States ; R03 AG064266/AG/NIA NIH HHS/United States ; RF1 NS112719/NS/NINDS NIH HHS/United States ; }, abstract = {This study establishes the physiological role of Fused in Sarcoma (FUS) in mitochondrial DNA (mtDNA) repair and highlights its implications to the pathogenesis of FUS-associated neurodegenerative diseases such as Amyotrophic lateral sclerosis (ALS). Endogenous FUS interacts with and recruits mtDNA Ligase IIIα (mtLig3) to DNA damage sites within mitochondria, a relationship essential for maintaining mtDNA repair and integrity in healthy cells. Using ALS patient-derived FUS mutant cell lines, a transgenic mouse model, and human autopsy samples, we discovered that compromised FUS functionality hinders mtLig3's repair role, resulting in increased mtDNA damage and mutations. These alterations cause various manifestations of mitochondrial dysfunction, particularly under stress conditions relevant to disease pathology. Importantly, rectifying FUS mutations in patient-derived induced pluripotent cells (iPSCs) preserves mtDNA integrity. Similarly, targeted introduction of human DNA Ligase 1 restores repair mechanisms and mitochondrial activity in FUS mutant cells, suggesting a potential therapeutic approach. Our findings unveil FUS's critical role in mitochondrial health and mtDNA repair, offering valuable insights into the mechanisms underlying mitochondrial dysfunction in FUS-associated neurodegeneration.}, } @article {pmid37502200, year = {2023}, author = {Syam, V and Safal, S and Bhutia, O and Singh, AK and Giri, D and Bhandari, SS and Panigrahi, R}, title = {A non-invasive method for prediction of neurodegenerative diseases using gait signal features.}, journal = {Procedia computer science}, volume = {218}, number = {}, pages = {1529-1541}, pmid = {37502200}, issn = {1877-0509}, support = {D43 TW009120/TW/FIC NIH HHS/United States ; }, abstract = {The steady degeneration of neurons is the hallmark of neurodegenerative illnesses, which are, by definition, incurable. Corticobasal Syndrome (CS), Huntington's Disease (HD), Dementia, Amyotrophic Lateral Sclerosis (ALS), Progressive supranuclear palsy (PSP) and Parkinson's Disease (PD) are some of the common neurodegenerative diseases which has impacted millions of people, predominantly among the older population. Various computational techniques, including but not limited to machine learning, are emerging as discrimination and detection of neuro-related diseases. This research proposed a machine learning-based framework to correctly detect PD, HD, and ALS from the gait signals of subjects both in binary and multi-class detection environment. The detection approach proposed here combines the classification power of Naïve Bayes and Logistic Regression jointly in a modern UltraBoost ensemble framework. The proposed method is unique in its ability to detect neuro diseases with a small number of gait features. The proposed approach ascertains most essential gait features through three state-of-the-art feature selection schemes, infinite feature selection, infinite latent feature selection and Sigmis feature selection. It has been observed that the gait signal features of the subjects are identified through Infinite Feature Selection manifests better detection results than the features obtained through Infinite Latent Feature and Sigmis feature selection while detecting Parkinson's and Huntington's Disease in a multi-class environment. So far as the binary detection environment is concern, the Amyotrophic lateral sclerosis is detected with 99.1% detection accuracy using 18 Sigmis gait features, with 99.1% sensitivity and 98.9% specificity, respectively. Similarly, Huntington's disease was detected with 94.2% detection accuracy, 94.2% sensitivity, and 94.5% specificity using 5 Sigmis gait features. Finally, Parkinson's disease was detected with 98.4% sensitivity, specificity, and detection accuracy.}, } @article {pmid37501540, year = {2023}, author = {Ma, Q and Xin, J and Peng, Q and Li, N and Sun, S and Hou, H and Ma, G and Wang, N and Zhang, L and Tam, KY and Dussmann, H and Prehn, JH and Wang, H and Ying, Z}, title = {UBQLN2 and HSP70 participate in Parkin-mediated mitophagy by facilitating outer mitochondrial membrane rupture.}, journal = {EMBO reports}, volume = {24}, number = {9}, pages = {e55859}, pmid = {37501540}, issn = {1469-3178}, mesh = {Humans ; Mitochondrial Membranes/metabolism ; *Amyotrophic Lateral Sclerosis/genetics ; Mitophagy ; *Frontotemporal Dementia/genetics ; Adaptor Proteins, Signal Transducing/genetics ; Autophagy-Related Proteins/genetics ; Proteasome Endopeptidase Complex/metabolism ; Ubiquitin/metabolism ; *Neurodegenerative Diseases/metabolism ; Transcription Factors/metabolism ; Ubiquitin-Protein Ligases/metabolism ; }, abstract = {Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are two aging-related neurodegenerative diseases that share common key features, including aggregation of pathogenic proteins, dysfunction of mitochondria, and impairment of autophagy. Mutations in ubiquilin 2 (UBQLN2), a shuttle protein in the ubiquitin-proteasome system (UPS), can cause ALS/FTD, but the mechanism underlying UBQLN2-mediated pathogenesis is still uncertain. Recent studies indicate that mitophagy, a selective form of autophagy which is crucial for mitochondrial quality control, is tightly associated with neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, and ALS. In this study, we show that after Parkin-dependent ubiquitination of damaged mitochondria, UBQLN2 is recruited to poly-ubiquitinated mitochondria through the UBA domain. UBQLN2 cooperates with the chaperone HSP70 to promote UPS-driven degradation of outer mitochondrial membrane (OMM) proteins. The resulting rupture of the OMM triggers the autophagosomal recognition of the inner mitochondrial membrane receptor PHB2. UBQLN2 is required for Parkin-mediated mitophagy and neuronal survival upon mitochondrial damage, and the ALS/FTD pathogenic mutations in UBQLN2 impair mitophagy in primary cultured neurons. Taken together, our findings link dysfunctional mitophagy to UBQLN2-mediated neurodegeneration.}, } @article {pmid37500993, year = {2023}, author = {Ludolph, A and Dupuis, L and Kasarskis, E and Steyn, F and Ngo, S and McDermott, C}, title = {Nutritional and metabolic factors in amyotrophic lateral sclerosis.}, journal = {Nature reviews. Neurology}, volume = {19}, number = {9}, pages = {511-524}, pmid = {37500993}, issn = {1759-4766}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism ; *Neurodegenerative Diseases ; Energy Metabolism ; Prognosis ; Disease Progression ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a complex neurodegenerative disease that is classically thought to impact the motor system. Over the past 20 years, research has started to consider the contribution of non-motor symptoms and features of the disease, and how they might affect ALS prognosis. Of the non-motor features of the disease, nutritional status (for example, malnutrition) and metabolic balance (for example, weight loss and hypermetabolism) have been consistently shown to contribute to more rapid disease progression and/or earlier death. Several complex cellular changes observed in ALS, including mitochondrial dysfunction, are also starting to be shown to contribute to bioenergetic failure. The resulting energy depletion in high energy demanding neurons makes them sensitive to apoptosis. Given that nutritional and metabolic stressors at the whole-body and cellular level can impact the capacity to maintain optimal function, these factors present avenues through which we can identify novel targets for treatment in ALS. Several clinical trials are now underway evaluating the effectiveness of modifying energy balance in ALS, making this article timely in reviewing the evidence base for metabolic and nutritional interventions.}, } @article {pmid37499984, year = {2023}, author = {Azoulay, L and St-Jean, A and Platt, RW}, title = {Response to Magnaterra et al's unveiling hydrochlorothiazide: Skin cancer risk and hidden interactions.}, journal = {Journal of the American Academy of Dermatology}, volume = {89}, number = {5}, pages = {e247-e248}, doi = {10.1016/j.jaad.2023.07.1012}, pmid = {37499984}, issn = {1097-6787}, } @article {pmid37499137, year = {2023}, author = {Illner, V and Tykalova, T and Skrabal, D and Klempir, J and Rusz, J}, title = {Automated Vowel Articulation Analysis in Connected Speech Among Progressive Neurological Diseases, Dysarthria Types, and Dysarthria Severities.}, journal = {Journal of speech, language, and hearing research : JSLHR}, volume = {66}, number = {8}, pages = {2600-2621}, doi = {10.1044/2023_JSLHR-22-00526}, pmid = {37499137}, issn = {1558-9102}, mesh = {Humans ; Dysarthria/etiology ; Speech/physiology ; *Cerebellar Ataxia ; *Parkinson Disease/complications ; Articulation Disorders ; Atrophy ; Speech Acoustics ; Speech Intelligibility ; }, abstract = {PURPOSE: Although articulatory impairment represents distinct speech characteristics in most neurological diseases affecting movement, methods allowing automated assessments of articulation deficits from the connected speech are scarce. This study aimed to design a fully automated method for analyzing dysarthria-related vowel articulation impairment and estimate its sensitivity in a broad range of neurological diseases and various types and severities of dysarthria.

METHOD: Unconstrained monologue and reading passages were acquired from 459 speakers, including 306 healthy controls and 153 neurological patients. The algorithm utilized a formant tracker in combination with a phoneme recognizer and subsequent signal processing analysis.

RESULTS: Articulatory undershoot of vowels was presented in a broad spectrum of progressive neurodegenerative diseases, including Parkinson's disease, progressive supranuclear palsy, multiple-system atrophy, Huntington's disease, essential tremor, cerebellar ataxia, multiple sclerosis, and amyotrophic lateral sclerosis, as well as in related dysarthria subtypes including hypokinetic, hyperkinetic, ataxic, spastic, flaccid, and their mixed variants. Formant ratios showed a higher sensitivity to vowel deficits than vowel space area. First formants of corner vowels were significantly lower for multiple-system atrophy than cerebellar ataxia. Second formants of vowels /a/ and /i/ were lower in ataxic compared to spastic dysarthria. Discriminant analysis showed a classification score of up to 41.0% for disease type, 39.3% for dysarthria type, and 49.2% for dysarthria severity. Algorithm accuracy reached an F-score of 0.77.

CONCLUSIONS: Distinctive vowel articulation alterations reflect underlying pathophysiology in neurological diseases. Objective acoustic analysis of vowel articulation has the potential to provide a universal method to screen motor speech disorders.

SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.23681529.}, } @article {pmid37498094, year = {2023}, author = {Christoforidou, E and Simoes, FA and Gordon, D and Talbot, K and Hafezparast, M}, title = {Aberrant dynein function promotes TDP-43 aggregation and upregulation of p62 in male mice harboring transgenic human TDP-43.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {}, number = {}, pages = {1-10}, doi = {10.1080/21678421.2023.2239276}, pmid = {37498094}, issn = {2167-9223}, abstract = {OBJECTIVE: Most TDP-43 mouse models of ALS do not display cytoplasmic mislocalisation or protein aggregation of TDP-43 in spinal motor neurons in vivo. Thus, we investigated whether a combination of defective dynein with a TDP-43 mutation could trigger TDP-43 pathology.

METHODS: Using immunohistochemical methods we examined the intracellular motor neuron pathology of the offspring of TDP-43[WT] and TDP-43[M337V] transgenic mice bred to heterozygous Loa mice, which carry an autosomal dominant mutation in dynein cytoplasmic 1 heavy chain 1 (Dync1h1).

RESULTS: These mice did not exhibit TDP-43 mislocalisation in spinal motor neurons, but the expression of mutant dynein in combination with wildtype human TDP-43 resulted in p62 upregulation and TDP-43 aggregation, thus partially recapitulating the human disease.

CONCLUSIONS: These findings provide new insights into the possible relationship between dynein and TDP-43 and could prove useful in future studies looking to elucidate the mechanism behind the TDP-43 pathology observed in ALS.}, } @article {pmid37497262, year = {2023}, author = {Ajjarapu, A and Feely, SME and Shy, ME and Trout, C and Zuchner, S and Moore, SA and Mathews, KD}, title = {Thirty-Year Follow-Up of Early Onset Amyotrophic Lateral Sclerosis with a Pathogenic Variant in SPTLC1.}, journal = {Case reports in neurology}, volume = {15}, number = {1}, pages = {146-152}, pmid = {37497262}, issn = {1662-680X}, support = {P50 NS053672/NS/NINDS NIH HHS/United States ; U54 NS065712/NS/NINDS NIH HHS/United States ; }, abstract = {Dominant mutations in serine palmitoyltransferase long chain base subunit 1 (SPTLC1), a known cause of hereditary sensory autonomic neuropathy type 1 (HSAN1), are a recently identified cause of juvenile amyotrophic lateral sclerosis (JALS) with slow progression. We present a case of SPTLC1-associated JALS followed for 30 years. She was initially evaluated at age 22 years for upper extremity weakness. She experienced gradual decline in muscle strength with development of weakness and hyperreflexia in lower extremities and diffuse fasciculations in the upper extremities at 26 years. She lost independent ambulation at age 45 years. Pulmonary function declined from a forced vital capacity of 94% predicted at 27 years to 49% predicted at 47 years, and she was hospitalized twice for respiratory failure. To our knowledge, this is the longest documented follow-up period of JALS caused by a de novo pathogenic variant in SPTLC1.}, } @article {pmid37496277, year = {2023}, author = {Melka, D and Demisse, H and Assefa, H and Zenebe, Y and A Ayele, B and Awraris, M and Gelan, Y and Kifelew, S and Fedlu, M and Tsehayneh, F and Zebenigus, M and Alemayehu, S and Tesfaye, H and Gulelat, H and Guta, T and Tafesse, A and Bekele, N and Saez, M and Veldink, JH and Al-Chalabi, A and Povedano, M and Al Khleifat, A}, title = {Epidemiological and clinical profile of amyotrophic lateral sclerosis in Ethiopia: a 5-year multicenter retrospective study.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {}, number = {}, pages = {1-9}, doi = {10.1080/21678421.2023.2238016}, pmid = {37496277}, issn = {2167-9223}, support = {MR/L501529/1/MRC_/Medical Research Council/United Kingdom ; }, abstract = {Background: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that results in progressive weakness of skeletal muscles including respiratory muscles. Epidemiological and clinical aspects of ALS are derived from a few world regions with very little representation of low- and middle-income countries. We therefore set out to determine the epidemiological and clinical phenotype of individuals with ALS in Ethiopia. Methods: Multicenter retrospective analysis was conducted using clinical records from ALS patients seen in Ethiopia at Tikur Anbessa Specialized Hospital and Yehuleshet specialty clinic between January 2016 and August 2021. The data collected included clinical characteristics, disease-related symptoms, a revised ALS functional rating scale, and medications. Results: Patients in Ethiopia had a younger age of onset with a mean age of disease onset of 51.9 years. 2.9% of patients had juvenile ALS, and the male-to-female ratio was almost 2:1. 4.9% had a positive family history of the disease. 68% of patients had spinal region involvement at onset, while 32% had bulbar region involvement at onset. Riluzole was used by 31% of ALS patients. 20.6% of patients had some respiratory symptoms, but none received a standard respiratory function assessment. 33.3% of patients were wheelchair-bound. Conclusion: In this retrospective study spanning 5 years, we examined the clinical phenotype of ALS in Ethiopian patients. Our findings suggest that most patients had clinically definite ALS with spinal region involvement. Further research, including genetic and epigenetic information, is necessary to understand the early onset of the disease in Ethiopia.}, } @article {pmid37496071, year = {2023}, author = {Onda-Ohto, A and Hasegawa-Ogawa, M and Matsuno, H and Shiraishi, T and Bono, K and Hiraki, H and Kanegae, Y and Iguchi, Y and Okano, HJ}, title = {Specific vulnerability of iPSC-derived motor neurons with TDP-43 gene mutation to oxidative stress.}, journal = {Molecular brain}, volume = {16}, number = {1}, pages = {62}, pmid = {37496071}, issn = {1756-6606}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/pathology ; DNA-Binding Proteins/genetics/metabolism ; *Induced Pluripotent Stem Cells/metabolism ; Motor Neurons/pathology ; Mutation/genetics ; Oxidative Stress ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a disease that affects motor neurons and has a poor prognosis. We focused on TAR DNA-binding protein 43 kDa (TDP-43), which is a common component of neuronal inclusions in many ALS patients. To analyze the contribution of TDP-43 mutations to ALS in human cells, we first introduced TDP-43 mutations into healthy human iPSCs using CRISPR/Cas9 gene editing technology, induced the differentiation of these cells into motor and sensory neurons, and analyzed factors that are assumed to be altered in or associated with ALS (cell morphology, TDP-43 localization and aggregate formation, cell death, TDP-43 splicing function, etc.). We aimed to clarify the pathological alterations caused solely by TDP-43 mutation, i.e., the changes in human iPSC-derived neurons with TDP-43 mutation compared with those with the same genetic background except TDP-43 mutation. Oxidative stress induced by hydrogen peroxide administration caused the death of TDP-43 mutant-expressing motor neurons but not in sensory neurons, indicating the specific vulnerability of human iPSC-derived motor neurons with TDP-43 mutation to oxidative stress. In our model, we observed aggregate formation in a small fraction of TDP-43 mutant-expressing motor neurons, suggesting that aggregate formation seems to be related to ALS pathology but not the direct cause of cell death. This study provides basic knowledge for elucidating the pathogenesis of ALS and developing treatments for the disease.}, } @article {pmid37495641, year = {2023}, author = {Caballero-Eraso, C and Carrera-Cueva, C and de Benito Zorrero, E and Lopez-Ramirez, C and Marin-Romero, S and Asensio-Cruz, MI and Barrot-Cortes, E and Jara-Palomares, L}, title = {Prospective study to evaluate quality of life in amyotrophic lateral sclerosis.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {12074}, pmid = {37495641}, issn = {2045-2322}, mesh = {Humans ; Female ; Middle Aged ; Aged ; Male ; *Quality of Life ; Prospective Studies ; *Amyotrophic Lateral Sclerosis ; Surveys and Questionnaires ; Patients ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative rare disease characterized by symptoms and signs in the upper and lower motor neurons, leading to progressive neuro-degeneration and muscle atrophy. Our objective was to analyse the quality of life (QoL) in patients with ALS and compare with general population and with patients with cancer. Prospective study from consecutive ALS patients in one center. In order to assess quality of life, during the first visit three questionnaires were administered: Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R), Short Form-36 (SF-36) and EuroQoL 5D (EQ-5D). We compared SF-36 of ALS patients with a reference population (n = 9151), and we compared the EQ-5D index score of ALS patients versus patients with cancer in the same area and in the same period (2015-2018). Between June 2015 and September 2017, 23 were included. The mean age was 65.1 ± 12.6 years and 56.5% were women. Compared with the general population, patients with ALS showed lowest QoL (p < 0.05) in all the dimensions, with a very important impairment in physical function (median: 0; p25-75: 0-10) and physical role (median: 0; p25-75: 0-6.25). In EQ-5D questionnaire, patients with ALS presented an EQ-5D index score of 0.21 ± 0.39 (mean ± standard deviation) with a visual analog scale (VAS) score of 0.32 ± 0.24. Compared with an oncological population, patients with ALS had a worse EQ-5D index score both clinically and statistically (0.21 ± 0.39 vs. 0.77 ± 0.27; p < 0.05). We demonstrate a poorer quality of life in patients with ALS is poor, and clinically and statistically worse than in patients with cancer or general population. New studies need to evaluate the impact of strategies in this population to improve the quality of life.}, } @article {pmid37495165, year = {2023}, author = {Sammeta, SS and Banarase, TA and Rahangdale, SR and Wankhede, NL and Aglawe, MM and Taksande, BG and Mangrulkar, SV and Upaganlawar, AB and Koppula, S and Kopalli, SR and Umekar, MJ and Kale, MB}, title = {Molecular understanding of ER-MT communication dysfunction during neurodegeneration.}, journal = {Mitochondrion}, volume = {72}, number = {}, pages = {59-71}, doi = {10.1016/j.mito.2023.07.005}, pmid = {37495165}, issn = {1872-8278}, mesh = {Humans ; Endoplasmic Reticulum/metabolism ; Mitochondria/metabolism ; Mitochondrial Membranes/metabolism ; *Neurodegenerative Diseases/metabolism ; *Parkinson Disease/pathology ; }, abstract = {Biological researchers are seeing organelles in a new light. These cellular entities have been believed to be singular and distinctive structures that performed specialized purposes for a very long time. But in recentpast years, scientists have learned that organelles become dynamic and make physical contact. Additionally, Biological processes are regulated by organelles interactions and its alteration play an important role in cell malfunctioning and several pathologies, including neurodegenerative diseases. Mitochondrial-ER contact sites (MERCS) have received considerable attention in the domain of cell homeostasis and dysfunction, specifically in the area of neurodegeneration. This is largely due to the significant role of this subcellular compartment in a diverse array of vital cellular functions, including Ca[2+] homeostasis, transport, bioenergetics and turnover, mitochondrial dynamics, apoptotic signaling, ER stress, and inflammation. A significant number of disease-associated proteins were found to physically interact with the ER-Mitochondria (ER-MT) interface, causing structural and/or functional alterations in this compartment. In this review, we summarize current knowledge about the structure and functions of the ER-MT contact sites, as well as the possible repercussions of their alteration in notable neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and fronto-temporal dementia. The constraints and complexities in defining the nature and origin of the highlighted defects in ER-MT communication, as well as their concise contribution to the neurodegenerative process, are illustrated in particular. The possibility of using MERCS as a potential drug target to prevent neuronal damage and ultimately neurodegeneration is the topic of our final discussion.}, } @article {pmid37494887, year = {2023}, author = {Bouvier, L and Green, JR and Tapia, CB and Tilton-Bolowsky, V and Maffei, MF and Fless, Z and Seaver, K and Huynh, A and Gutz, SE and Martino, R and Abrahao, A and Berry, J and Zinman, L and Yunusova, Y}, title = {Amyotrophic Lateral Sclerosis-Bulbar Dysfunction Index-Remote: Test-Retest and Interrater Reliability of Candidate Items.}, journal = {American journal of speech-language pathology}, volume = {32}, number = {4S}, pages = {1884-1900}, pmid = {37494887}, issn = {1558-9110}, support = {R01 DC017291/DC/NIDCD NIH HHS/United States ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis ; Reproducibility of Results ; Neurologic Examination ; Deglutition ; Severity of Illness Index ; }, abstract = {PURPOSE: The primary aim of this study was to establish the reliability of candidate items as a step in the development of the Amyotrophic Lateral Sclerosis-Bulbar Dysfunction Index-Remote (ALS-BDI-Remote), a novel tool being developed for the detection and monitoring of bulbar signs and symptoms in remote settings.

METHOD: The set of candidate items included 40 items covering three domains: cranial nerve examination, auditory-perceptual evaluation, and functional assessment. Forty-eight participants diagnosed with ALS and exhibiting a range of bulbar disease severity were included. Data collection for each participant took place on Zoom over three sessions. During Session 1, the participants were instructed to adjust their Zoom settings and to optimize their recording environment (e.g., lighting, background noise). Their cognition and eating were screened to determine their ability to follow instructions and their eligibility to perform the swallowing and chewing tasks. During Session 2, two speech-language pathologists (SLPs) administered the tool consecutively to determine the items' interrater reliability. During Session 3, one of the SLPs readministered the tool within 2 weeks of Session 1 to assess test-retest reliability. The reliability of each item was estimated using weighted kappa and the percentage of agreement. To be considered reliable, the items had to reach a threshold of 0.5 weighted kappa or 80% percentage agreement (if skewed distribution of the scores) for both interrater and test-retest reliability.

RESULTS: In total, 33 of the 40 candidate items reached the reliability cutoff for both reliability analyses. All assessment domains included reliable items. Items requiring very good visualization of structures or movements were generally less reliable.

CONCLUSIONS: This study resulted in the selection of reliable items to be included in the next version of the ALS-BDI-Remote, which will undergo psychometric evaluation (reliability, validity, and responsiveness analyses). Additionally, the results contributed to our understanding of the remote administration of SLP assessments for telehealth applications.}, } @article {pmid37494873, year = {2023}, author = {Ramya, L and Helina Hilda, S}, title = {Structural dynamics of moonlighting intrinsically disordered proteins - A black box in multiple sclerosis.}, journal = {Journal of molecular graphics & modelling}, volume = {124}, number = {}, pages = {108572}, doi = {10.1016/j.jmgm.2023.108572}, pmid = {37494873}, issn = {1873-4243}, mesh = {Humans ; *Multiple Sclerosis ; *Intrinsically Disordered Proteins ; Myelin Proteins ; Membrane Proteins ; }, abstract = {Multiple Sclerosis (MS) is a demyelinating disease of the central nervous system that disturbs the flow of brain signals to other parts of the body. The actual cause of the disease is still not apparent. The intrinsically disordered proteins (IDP) play a crucial role in neurodegenerative diseases like Alzheimer's, Lewy bodies, Parkinson's, Amyotrophic Lateral Sclerosis, Multiple Sclerosis, etc. In MS, it was known that the immune system attacks the proteins like Myelin Basic Protein (MBP), Myelin-associated Oligodendrocyte Basic protein (MOBP), Myelin-Associated Protein (MAG), and Myelin Proteolipid Protein (PLP) and this leads to demyelination causing MS. Here the proteins MBP and MOBP are both moonlighting intrinsically disordered proteins and exist between the myelin sheath, unlike MAG which is a transmembrane protein. The main focus of the article was to examine the significant role of proteins intrinsically disordered regions (IDR) in maintaining their function. Molecular dynamics simulation studies were performed to study the conformational dynamics of these protein IDRs both in water and near the myelin sheath. The results suggest that the IDR dominates the structural dynamics of these proteins and IDR in both proteins was responsible for their interaction with the myelin sheath. Interestingly, it was noted that the known epitopes MBP83-96 and MOBP65-87 in the IDR have no interaction with the myelin sheath. Thus when the protein remains intrinsically disordered it maintains the proper function and myelin integrity and if it adopts folds the region was identified as an epitope by the immune system leading to demyelination causing MS.}, } @article {pmid37494786, year = {2023}, author = {Jin, S and Zhang, L and Wang, L}, title = {Kaempferol, a potential neuroprotective agent in neurodegenerative diseases: From chemistry to medicine.}, journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie}, volume = {165}, number = {}, pages = {115215}, doi = {10.1016/j.biopha.2023.115215}, pmid = {37494786}, issn = {1950-6007}, mesh = {Humans ; *Neurodegenerative Diseases/drug therapy/pathology ; *Neuroprotective Agents/pharmacology/therapeutic use/chemistry ; *Amyotrophic Lateral Sclerosis/drug therapy ; Kaempferols/pharmacology/therapeutic use ; *Alzheimer Disease/drug therapy ; *Parkinson Disease/drug therapy ; *Huntington Disease/drug therapy ; }, abstract = {Neurodegenerative diseases (NDDs) encompass a range of conditions that involve progressive deterioration and dysfunction of the nervous system. Some of the common NDDs include Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS). Although significant progress has been made in understanding the pathological mechanisms of NDDs in recent years, the development of targeted and effective drugs for their treatment remains challenging. Kaempferol is a flavonoid whose derivatives include kaempferol-O-rhamnoside, 3-O-β-rutinoside/6-hydroxykaempferol 3,6-di-O-β-d-glucoside, and kaempferide. Emerging studies have suggested that kaempferol and its derivatives possess neuroprotective properties and may have potential therapeutic benefits in NDDs. Here, we aimed to provide a theoretical basis for the use of kaempferol and its derivatives in the clinical treatment of NDDs. We systematically reviewed the literature in the PubMed, Web of Science, and Science Direct databases until June 2022 using the search terms "kaempferol," "kaempferol derivatives," "NDDs," "pharmacokinetics," and "biosynthesis" according to the reporting items for systematic review (PRISMA) standard. Based on combined results of in vivo and in vitro studies, we summarize the basic mechanisms and targets of kaempferol and its derivatives in the management of AD, PD, HD, and ALS. Kaempferol and its derivatives exert a neuroprotective role mainly by preventing the deposition of amyloid fibrils (such as Aβ, tau, and α-synuclein), inhibiting microglia activation, reducing the release of inflammatory factors, restoring the mitochondrial membrane to prevent oxidative stress, protecting the blood-brain barrier, and inhibiting specific enzyme activities (such as cholinesterase). Kaempferol and its derivatives are promising natural neuroprotective agents. By determining their pharmacological mechanism, kaempferol and its derivatives may be new candidate drugs for the treatment of NDDs.}, } @article {pmid37493896, year = {2023}, author = {Lo Piccolo, L and Umegawachi, T and Yeewa, R and Potikanond, S and Nimlamool, W and Prachayasittikul, V and Gotoh, Y and Yoshida, H and Yamaguchi, M and Jantrapirom, S}, title = {A Novel Drosophila-based Drug Repurposing Platform Identified Fingolimod As a Potential Therapeutic for TDP-43 Proteinopathy.}, journal = {Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics}, volume = {20}, number = {5}, pages = {1330-1346}, pmid = {37493896}, issn = {1878-7479}, mesh = {Animals ; *Amyotrophic Lateral Sclerosis/genetics ; DNA-Binding Proteins/genetics ; Drosophila/metabolism ; Drug Repositioning ; Fingolimod Hydrochloride/therapeutic use ; *TDP-43 Proteinopathies/pathology ; }, abstract = {Pathogenic changes to TAR DNA-binding protein 43 (TDP-43) leading to alteration of its homeostasis are a common feature shared by several progressive neurodegenerative diseases for which there is no effective therapy. Here, we developed Drosophila lines expressing either wild type TDP-43 (WT) or that carrying an Amyotrophic Lateral Sclerosis /Frontotemporal Lobar Degeneration-associating G384C mutation that recapitulate several aspects of the TDP-43 pathology. To identify potential therapeutics for TDP-43-related diseases, we implemented a drug repurposing strategy that involved three consecutive steps. Firstly, we evaluated the improvement of eclosion rate, followed by the assessment of locomotive functions at early and late developmental stages. Through this approach, we successfully identified fingolimod, as a promising candidate for modulating TDP-43 toxicity. Fingolimod exhibited several beneficial effects in both WT and mutant models of TDP-43 pathology, including post-transcriptional reduction of TDP-43 levels, rescue of pupal lethality, and improvement of locomotor dysfunctions. These findings provide compelling evidence for the therapeutic potential of fingolimod in addressing TDP-43 pathology, thereby strengthening the rationale for further investigation and consideration of clinical trials. Furthermore, our study demonstrates the utility of our Drosophila-based screening pipeline in identifying novel therapeutics for TDP-43-related diseases. These findings encourage further scale-up screening endeavors using this platform to discover additional compounds with therapeutic potential for TDP-43 pathology.}, } @article {pmid37493444, year = {2023}, author = {Gonzalez Deniselle, MC and Bettini, M and Garrido, RM and Meyer, M and Lara, A and Garay, LI and Casas, S and Fulgenzi, E and Nuñez, M and Rugiero, MF and De Nicola, AF and Gargiulo-Monachelli, G}, title = {Exposure to endogenous and exogenous sex hormones and reproductive history influence prognosis in women with ALS.}, journal = {Muscle & nerve}, volume = {68}, number = {4}, pages = {414-421}, doi = {10.1002/mus.27942}, pmid = {37493444}, issn = {1097-4598}, mesh = {Male ; Humans ; Female ; *Amyotrophic Lateral Sclerosis ; Reproductive History ; *Neurodegenerative Diseases/complications ; Gonadal Steroid Hormones ; Prognosis ; Risk Factors ; Steroids ; }, abstract = {INTRODUCTION/AIMS: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a higher incidence in men suggesting an influence of sex steroids. Our objective was to investigate past exposure to endogenous and synthetic steroids in female ALS patients and controls.

METHODS: We administered a questionnaire to 158 postmenopausal women (75 ALS patients and 83 controls). We calculated reproductive time span (RTS), lifetime endogenous estrogen (LEE) and progesterone exposures (LPE), oral contraceptive pill (OCP) use, and reproductive history.

RESULTS: ALS patients showed shorter LEE and LPE, a lower proportion of breast cancer, and 11% showed no history of pregnancies vs. 4% of controls. Odds ratios (ORs) showed that <17 y of LEE and a delayed menarche (>13 y) constitute risk factors for ALS [OR = 2.1 (95% confidence interval {CI}, 1.08-4.2); and OR = 2.4 (95% CI, 1.1-5.1) respectively]. According to Cox survival analysis, for each year the LEE increased over 17 y, it was independently associated with longer survival [hazard ratio (HR) = 0.37 (95% CI, 0.16-0.85)] after adjusting for smoking, age and site of onset. Multivariate regression analysis demonstrated that for each month using OCP for longer than 40 mo increased the risk of ALS [adjusted OR = 4.1 (95% CI, 1.2-13.8)].

DISCUSSION: Thus, longer exposure to endogenous female sex steroids increased survival and reduced ALS susceptibility. In contrast, longer exposure to synthetic sex steroids showed a negative impact by reducing the production of endogenous female sex steroids or due to crossover with other steroid receptors. Given the neuroprotective effects of sex steroids, we suggest that abnormalities of neuroendocrine components may alter motor function in women with ALS.}, } @article {pmid37493197, year = {2024}, author = {Sun, Y and Benatar, M and Mascías Cadavid, J and Ennist, D and Wicks, P and Staats, K and Beauchamp, M and Jhooty, S and Pattee, G and Brown, A and Bertorini, T and Barkhaus, P and Bromberg, M and Carter, G and Bedlack, R and Li, X}, title = {ALSUntangled #71: Nuedexta.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {25}, number = {1-2}, pages = {218-222}, doi = {10.1080/21678421.2023.2239292}, pmid = {37493197}, issn = {2167-9223}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy ; *Dextromethorphan/therapeutic use ; Drug Combinations ; *Quinidine/therapeutic use ; }, abstract = {Nuedexta is a combination of dextromethorphan hydrobromide and quinidine sulfate and was approved by the Food and Drug Administration (FDA) in 2010 to treat pseudobulbar affect (PBA). There have since been anecdotal case reports of bulbar function improvements after Nuedexta treatment. Here, we review the off-label use of Nuedexta for improving bulbar function in people with ALS. Nuedexta has plausible mechanisms for protecting brain stem motor neurons via its effects on S1R and glutamate excitotoxicity. Recent clinical trials support that Nuedexta can improve bulbar function in PALS, with or without PBA. Nuedexta causes mild to moderate side effects. Based on this information, we support considering Nuedexta treatment for bulbar dysfunction in ALS patients with or without PBA.}, } @article {pmid37491680, year = {2023}, author = {Vasta, R and Callegaro, S and Sgambetterra, S and Cabras, S and Di Pede, F and De Mattei, F and Matteoni, E and Grassano, M and Bombaci, A and De Marco, G and Fuda, G and Marchese, G and Palumbo, F and Canosa, A and Mazzini, L and De Marchi, F and Moglia, C and Manera, U and Chiò, A and Calvo, A}, title = {Presymptomatic geographical distribution of ALS patients suggests the involvement of environmental factors in the disease pathogenesis.}, journal = {Journal of neurology}, volume = {270}, number = {11}, pages = {5475-5482}, pmid = {37491680}, issn = {1432-1459}, support = {grant RF-2016-02362405//Ministero della Salute/ ; FP7/2007-2013 under grant agreement 259867//Seventh Framework Programme/ ; PRIN//Ministero dell'Istruzione, dell'Università e della Ricerca/ ; grant 2017SNW5MB//Ministero dell'Istruzione, dell'Università e della Ricerca/ ; Brainteaser Project//European Union's Horizon 2020 research and innovation programme/ ; grant GA101017598//European Union's Horizon 2020 research and innovation programme/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/epidemiology/etiology ; Risk ; Incidence ; Cluster Analysis ; }, abstract = {BACKGROUND: Given that the pathogenetic process of ALS begins many years prior to its clinical onset, examining patients' residential histories may offer insights on the disease risk factors. Here, we analyzed the spatial distribution of a large ALS cohort in the 50 years preceding the disease onset.

METHODS: Data from the PARALS register were used. A spatial cluster analysis was performed at the time of disease onset and at 1-year intervals up to 50 years prior to that.

RESULTS: A total of 1124 patients were included. The analysis revealed a higher-incidence cluster in a large area (435,000 inhabitants) west of Turin. From 9 to 2 years before their onset, 105 cases were expected and 150 were observed, resulting in a relative risk of 1.49 (P = 0.04). We also found a surprising high number of patients pairs (51) and trios (3) who lived in the same dwelling while not being related. Noticeably, these occurrences were not observed in large dwellings as we would have expected. The probability of this occurring in smaller buildings only by chance was very low (P = 0.01 and P = 0.04 for pairs and trios, respectively).

CONCLUSIONS: We identified a higher-incidence ALS cluster in the years preceding the disease onset. The cluster area being densely populated, many exposures could have contributed to the high incidence ALS cluster, while we could not find a shared exposure among the dwellings where multiple patients had lived. However, these findings support that exogenous factors are likely involved in the ALS pathogenesis.}, } @article {pmid37491426, year = {2023}, author = {Yazar, V and Kühlwein, JK and Knehr, A and Grozdanov, V and Ekici, AB and Ludolph, AC and Danzer, KM}, title = {Impaired ATF3 signaling involves SNAP25 in SOD1 mutant ALS patients.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {12019}, pmid = {37491426}, issn = {2045-2322}, mesh = {Animals ; Mice ; *Amyotrophic Lateral Sclerosis/genetics/metabolism ; Leukocytes, Mononuclear/metabolism ; Mice, Transgenic ; Mutation ; Superoxide Dismutase/genetics/metabolism ; Superoxide Dismutase-1/genetics ; }, abstract = {Epigenetic remodeling is emerging as a critical process for several neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). Genetics alone fails to explain the etiology of ALS, the investigation of the epigenome might therefore provide novel insights into the molecular mechanisms of the disease. In this study, we interrogated the epigenetic landscape in peripheral blood mononuclear cells (PBMCs) of familial ALS (fALS) patients with either chromosome 9 open reading frame 72 (C9orf72) or superoxide dismutase 1 (SOD1) mutation and aimed to identify key epigenetic footprints of the disease. To this end, we used an integrative approach that combines chromatin immunoprecipitation targeting H3K27me3 (ChIP-Seq) with the matching gene expression data to gain new insights into the likely impact of blood-specific chromatin remodeling on ALS-related molecular mechanisms. We demonstrated that one of the hub molecules that modulates changes in PBMC transcriptome in SOD1-mutant ALS patients is ATF3, which has been previously reported in an SOD1[G93A] mouse model. We also identified potential suppression of SNAP25, with impaired ATF3 signaling in SOD1-mutant ALS blood. Together, our study shed light on the mechanistic underpinnings of SOD1 mutations in ALS.}, } @article {pmid37491361, year = {2023}, author = {Aousji, O and Feldengut, S and Antonucci, S and Schön, M and Boeckers, TM and Matschke, J and Mawrin, C and Ludolph, AC and Del Tredici, K and Roselli, F and Braak, H}, title = {Patterns of synaptic loss in human amyotrophic lateral sclerosis spinal cord: a clinicopathological study.}, journal = {Acta neuropathologica communications}, volume = {11}, number = {1}, pages = {120}, pmid = {37491361}, issn = {2051-5960}, mesh = {Humans ; Mice ; Animals ; *Amyotrophic Lateral Sclerosis/pathology ; Retrospective Studies ; Motor Neurons/metabolism ; Spinal Cord/pathology ; }, abstract = {Amyotrophic Lateral Sclerosis (ALS) is mainly characterized by the degeneration of corticospinal neurons and spinal α-motoneurons; vulnerable cells display prominent pTDP-43 inclusions. Evidence gathered from genetics, murine models, and iPSC-derived neurons point to the early involvement of synapses in the disease course and their crucial role in the pathogenic cascade. However, pathology studies, with specimens from large post-mortem cohorts, mapping the pattern of synaptic disturbances over clinical and neuropathological hallmarks of disease progression, are currently not available. Thus, the appearance and progression of synaptic degeneration in human ALS patients are currently not known, preventing a full validation of the murine and in vitro models. Here, we investigated the loss of synaptophysin-positive terminals in cervical, thoracic, and lumbar spinal cord samples from a retrospective cohort of n = 33 ALS patients and n = 8 healthy controls, and we correlated the loss of synapses against clinicodemographic features and neuropathological ALS stage. We found that, although dorsal and intermediate spinal cord laminae do not lose synapses, ALS patients displayed a substantial but variable loss of synapses in the ventral horn of lumbar and cervical spinal cord. The amount of synaptic loss was predicted by disease duration, by the clinical site of onset, and by the loss of α-motoneurons, although not by the fraction of pTDP-43-immunopositive α-motoneurons. Taken together, our findings validate the synaptic pathology observed in other models and suggest that pathogenic pathways unfolding in the spinal microenvironment are critical to the progressive disassembly of local synaptic connectivity.}, } @article {pmid37490673, year = {2023}, author = {Kovrazhkina, EA and Serdyuk, AV and Razinskaya, OD and Shurdumova, MH and Vyatkina, NV and Baranova, EA}, title = {[Myasthenic syndrome in a patient with end-stage amyotrophic lateral sclerosis].}, journal = {Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova}, volume = {123}, number = {7}, pages = {102-107}, doi = {10.17116/jnevro2023123071102}, pmid = {37490673}, issn = {1997-7298}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/complications/diagnosis/therapy ; *Myasthenia Gravis/complications/diagnosis ; *Lambert-Eaton Myasthenic Syndrome ; }, abstract = {Amyotrophic lateral sclerosis (ALS) and myasthenia gravis are diseases with similar clinical features but different prognosis and approach to treatment. It is possible as an extremely rare combination of these diseases, as well as myasthenia gravis with signs of ALS (MuSK-positive), as well as ALS, accompanied by myasthenic syndrome. Latter option is the most common. Myasthenic syndrome accompanying the ALS characterized by pathological muscle fatigue signs, symptoms variability during the day, partial sensitivity to neostigmine, M-wave decrements detection during electromyographyc study. We present a case of a patient with terminal ALS and myasthenic syndrome. The main pathogenesis theories of this condition and the differential diagnosis of ALS and myasthenia gravis are discussed.}, } @article {pmid37490576, year = {2023}, author = {Beyermann, A and Asp, M and Godskesen, T and Söderman, M}, title = {Nurses' challenges when supporting the family of patients with ALS in specialized palliative home care: A qualitative study.}, journal = {International journal of qualitative studies on health and well-being}, volume = {18}, number = {1}, pages = {2238984}, pmid = {37490576}, issn = {1748-2631}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy/psychology ; Palliative Care/psychology ; *Home Care Services ; Family/psychology ; Qualitative Research ; *Nurses ; }, abstract = {PURPOSE: Being a family member to someone who has amyotrophic lateral sclerosis (ALS) is demanding and often requires sacrificing a lot. Family members can experience fatigue, anxiety, guilt and need support. The aim was to explore registered nurses' (RNs') experiences of providing support to the families of patients with ALS within specialized palliative home care (SPHC).

METHODS: A qualitative explorative design. Interviews were conducted with RNs (n = 11) from five SPHCs in Sweden and analysed using qualitative content analysis.

RESULTS: The results emerged in the following categories:"To support in an increasingly difficult everyday life", based on the sub-categories: "Creating a trusting relationship", "Balancing between the needs of patients and their families", and "Sharing knowledge about dying to the families";"To support in emotionally challenging situations", based on the sub-categories: "Harbouring family members' difficult feelings", "Providing support even though the situation is unpleasant" and "Being able to give support by receiving confirmation and support from others".

CONCLUSIONS: RNs working in SPHC have an important role in providing support in several ways to the families of patients with ALS, through facilitating their everyday life and giving emotional support when needed, based on the needs of both patients and the families.}, } @article {pmid37489926, year = {2023}, author = {Greensmith, L and Bryson, JB}, title = {The cholesterol depleting agent, (2-Hydroxypropyl)-ß-cyclodextrin, does not affect disease progression in SOD1[G93A] mice.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {}, number = {}, pages = {1-7}, doi = {10.1080/21678421.2023.2239867}, pmid = {37489926}, issn = {2167-9223}, abstract = {Objective: Previously, we demonstrated that Amyloid Precursor Protein (APP) contributes to pathology in the SOD1[G93A] mouse model of ALS and that genetic ablation of APP in SOD1[G93A] mice significantly improved multiple disease parameters, including muscle innervation and motor neuron survival. We also observed elevated levels of potentially neurotoxic Aß peptides that have been implicated in Alzheimer's Disease (AD) pathogenesis, within motor neurons and astrocytes in SOD1[G93A] mice. More recently, it has been shown that blocking Aß production improves outcome measures in SOD1[G93A] mice. The cyclodextrin, (2-Hydroxypropyl)-ß-cyclodextrin (HP-β-CD), has previously been shown to deplete intraneuronal unesterified cholesterol, resulting in effective reduction of Aß production and amelioration of disease progression in mouse models of AD and Niemann Pick Type C (NPC) disease. Here, we tested whether HP-β-CD could also improve phenotypic progression in SOD1[G93A] mice. Methods: Pre-symptomatic male SOD1[G93A] mice were randomly assigned to the following treatment groups: HP-β-CD (4000mg/kg, n = 9) or vehicle (saline; n = 10), delivered by weekly subcutaneous injection, commencing at 67 days of age. Longitudinal grip-strength and body mass analysis was performed until late-stage disease (120 days of age), followed by in vivo bilateral isometric muscle tension analysis of tibialis anterior (TA) and extensor digitorum longus (EDL) muscles. Results: HP-β-CD administration had no effect on body mass or grip-strength compared to vehicle treated SOD1[G93A] mice. Similarly, HP-β-CD treatment had no effect on muscle force, contractile properties or motor unit number estimates (MUNE) at late-stage disease in SOD1[G93A] mice. Conclusion: This study shows that HP-β-CD does not confer any therapeutic benefit in SOD1[G93A] mice. However, the absence of detrimental effects is informative, given the common use of cyclodextrins as complexing agents for other pharmaceutical products, their standalone therapeutic potential and the emerging association between dyslipidaemia and ALS progression.}, } @article {pmid37489441, year = {2023}, author = {Ramakrishna, K and Nalla, LV and Naresh, D and Venkateswarlu, K and Viswanadh, MK and Nalluri, BN and Chakravarthy, G and Duguluri, S and Singh, P and Rai, SN and Kumar, A and Singh, V and Singh, SK}, title = {WNT-β Catenin Signaling as a Potential Therapeutic Target for Neurodegenerative Diseases: Current Status and Future Perspective.}, journal = {Diseases (Basel, Switzerland)}, volume = {11}, number = {3}, pages = {}, pmid = {37489441}, issn = {2079-9721}, abstract = {Wnt/β-catenin (WβC) signaling pathway is an important signaling pathway for the maintenance of cellular homeostasis from the embryonic developmental stages to adulthood. The canonical pathway of WβC signaling is essential for neurogenesis, cell proliferation, and neurogenesis, whereas the noncanonical pathway (WNT/Ca[2+] and WNT/PCP) is responsible for cell polarity, calcium maintenance, and cell migration. Abnormal regulation of WβC signaling is involved in the pathogenesis of several neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), and spinal muscular atrophy (SMA). Hence, the alteration of WβC signaling is considered a potential therapeutic target for the treatment of neurodegenerative disease. In the present review, we have used the bibliographical information from PubMed, Google Scholar, and Scopus to address the current prospects of WβC signaling role in the abovementioned neurodegenerative diseases.}, } @article {pmid37489031, year = {2023}, author = {Rahimzadeh Goradel, R and Sattarpour, R and Hooshyari, Z and Taebi, M and Ghavampour, A and Jazani, MR and Sarraf, P}, title = {Examining the validity and reliability of the Persian version of the MiND-B questionnaire in ALS patients.}, journal = {Brain and behavior}, volume = {13}, number = {9}, pages = {e3167}, pmid = {37489031}, issn = {2162-3279}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/psychology ; Reproducibility of Results ; *Cognition Disorders ; Cognition/physiology ; Surveys and Questionnaires ; }, abstract = {BACKGROUND: In addition to affecting the nerves and muscles, amyotrophic lateral sclerosis (ALS) disease also affects the behavior and cognition of patients. In this study, we examine the validity and reliability of the Persian version of Motor Neuron Disease Behavioral instrument (MiND-B) questionnaire to investigate behavioral changes in Persian-speaking ALS patients.

METHODS: Forty-six Persian-speaking patients with ALS filled out the MiND-B questionnaire. Then, the overall scores and each of the domains of this questionnaire were statistically analyzed.

RESULTS: Cronbach's alpha coefficient was calculated .70 for the whole questionnaire. To check the validity of the questionnaire, the correlation of its scores with the Edinburgh Cognitive and Behavioral ALS screen (ECAS-A) questionnaire was taken, and this correlation was significant (p = .038).

CONCLUSION: The findings of this study show that the Persian version of the MiND-B questionnaire has the necessary validity and reliability to investigate behavioral changes in Persian-speaking patients with ALS.}, } @article {pmid37488957, year = {2023}, author = {Lee, J and Kim, A and Choi, SJ and Cho, E and Seo, J and Oh, SI and Jung, J and Kim, JS and Sung, JJ and Abrahams, S and Hong, YH}, title = {Development and Validation of the Korean Version of the Edinburgh Cognitive and Behavioral Amyotrophic Lateral Sclerosis Screen (ECAS-K).}, journal = {Journal of clinical neurology (Seoul, Korea)}, volume = {19}, number = {5}, pages = {454-459}, pmid = {37488957}, issn = {1738-6586}, support = {2020R1F1A1072153/NRF/National Research Foundation of Korea/Korea ; }, abstract = {BACKGROUND AND PURPOSE: Cognitive and behavioral changes are common in amyotrophic lateral sclerosis (ALS), with about 15% of patients presenting with overt frontotemporal dementia and 30%-50% with varying degrees of impairments. We aimed to develop and validate the Korean version of the Edinburgh Cognitive and Behavioral ALS Screen (ECAS-K), a brief multidomain assessment tool developed for ALS patients with physical disability.

METHODS: We developed the ECAS-K according to the translation guidelines, and administered it to 38 patients with ALS and 26 age- and education-level-matched controls. We also administered the Montreal Cognitive Assessment (MoCA) and Frontal Assessment Battery (FAB) to investigate convergent validity, and the Center for Neurologic Study-Liability Scale to assess the association between pseudobulbar affect and cognitive/behavioral changes.

RESULTS: Internal consistency among the ECAS-K test items was found to be high, with a Cronbach's alpha of 0.87. Significant differences were found between patients with ALS and the controls in language, fluency, and memory functions (p<0.05). Abnormal performance based on the ECAS total score was noted in 39.4% of patients, and 66.6% presented behavioral changes in at least one domain. Significant correlations were observed between the scores of the ECAS-K and those of other cognitive screening tools (MoCA and FAB, with correlation coefficients of 0.69 and 0.55, respectively; p<0.01).

CONCLUSIONS: We developed and validated the ECAS-K which could be used as an effective tool to screen the cognitive and behavioral impairments in Korean patients with ALS.}, } @article {pmid37488888, year = {2024}, author = {Zhou, M and Li, S and Huang, C}, title = {Physiological and pathological functions of circular RNAs in the nervous system.}, journal = {Neural regeneration research}, volume = {19}, number = {2}, pages = {342-349}, pmid = {37488888}, issn = {1673-5374}, abstract = {Circular RNAs (circRNAs) are a class of covalently closed single-stranded RNAs that are expressed during the development of specific cells and tissues. CircRNAs play crucial roles in physiological and pathological processes by sponging microRNAs, modulating gene transcription, controlling the activity of certain RNA-binding proteins, and producing functional peptides. A key focus of research at present is the functionality of circRNAs in the nervous system and several advances have emerged over the last 2 years. However, the precise role of circRNAs in the nervous system has yet to be comprehensively reviewed. In this review, we first summarize the recently described roles of circRNAs in brain development, maturity, and aging. Then, we focus on the involvement of circRNAs in various diseases of the central nervous system, such as brain cancer, chronic neurodegenerative diseases, acute injuries of the nervous system, and neuropathic pain. A better understanding of the functionality of circRNAs will help us to develop potential diagnostic, prognostic, and therapeutic strategies to treat diseases of the nervous system.}, } @article {pmid37488879, year = {2024}, author = {Yu, Z and Teng, Y and Yang, J and Yang, L}, title = {The role of exosomes in adult neurogenesis: implications for neurodegenerative diseases.}, journal = {Neural regeneration research}, volume = {19}, number = {2}, pages = {282-288}, pmid = {37488879}, issn = {1673-5374}, abstract = {Exosomes are cup-shaped extracellular vesicles with a lipid bilayer that is approximately 30 to 200 nm in thickness. Exosomes are widely distributed in a range of body fluids, including urine, blood, milk, and saliva. Exosomes exert biological function by transporting factors between different cells and by regulating biological pathways in recipient cells. As an important form of intercellular communication, exosomes are increasingly being investigated due to their ability to transfer bioactive molecules such as lipids, proteins, mRNAs, and microRNAs between cells, and because they can regulate physiological and pathological processes in the central nervous system. Adult neurogenesis is a multistage process by which new neurons are generated and migrate to be integrated into existing neuronal circuits. In the adult brain, neurogenesis is mainly localized in two specialized niches: the subventricular zone adjacent to the lateral ventricles and the subgranular zone of the dentate gyrus. An increasing body of evidence indicates that adult neurogenesis is tightly controlled by environmental conditions with the niches. In recent studies, exosomes released from different sources of cells were shown to play an active role in regulating neurogenesis both in vitro and in vivo, thereby participating in the progression of neurodegenerative disorders in patients and in various disease models. Here, we provide a state-of-the-art synopsis of existing research that aimed to identify the diverse components of exosome cargoes and elucidate the therapeutic potential of exosomal contents in the regulation of neurogenesis in several neurodegenerative diseases. We emphasize that exosomal cargoes could serve as a potential biomarker to monitor functional neurogenesis in adults. In addition, exosomes can also be considered as a novel therapeutic approach to treat various neurodegenerative disorders by improving endogenous neurogenesis to mitigate neuronal loss in the central nervous system.}, } @article {pmid37488847, year = {2024}, author = {Huber, CC and Wang, H}, title = {Pathogenic and therapeutic role of exosomes in neurodegenerative disorders.}, journal = {Neural regeneration research}, volume = {19}, number = {1}, pages = {75-79}, pmid = {37488847}, issn = {1673-5374}, support = {P20 GM103443/GM/NIGMS NIH HHS/United States ; P20 RR016479/RR/NCRR NIH HHS/United States ; RF1 AG072510/AG/NIA NIH HHS/United States ; T32 GM136503/GM/NIGMS NIH HHS/United States ; }, abstract = {Neurodegenerative disorders affect millions of people worldwide, and the prevalence of these disorders is only projected to rise as the number of people over 65 will drastically increase in the coming years. While therapies exist to aid in symptomatic relief, effective treatments that can stop or reverse the progress of each neurodegenerative disease are lacking. Recently, research on the role of extracellular vesicles as disease markers and therapeutics has been intensively studied. Exosomes, 30-150 nm in diameter, are one type of extracellular vesicles facilitating cell-to-cell communication. Exosomes are thought to play a role in disease propagation in a variety of neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. Accordingly, the exosomes derived from the patients are an invaluable source of disease biomarkers. On the other hand, exosomes, especially those derived from stem cells, could serve as a therapeutic for these disorders, as seen by a rapid increase in clinical trials investigating the therapeutic efficacy of exosomes in different neurological diseases. This review summarizes the pathological burden and therapeutic approach of exosomes in neurodegenerative disorders. We also highlight how heat shock increases the yield of exosomes while still maintaining their therapeutic efficacy. Finally, this review concludes with outstanding questions that remain to be addressed in exosomal research.}, } @article {pmid37488208, year = {2023}, author = {Aly, A and Laszlo, ZI and Rajkumar, S and Demir, T and Hindley, N and Lamont, DJ and Lehmann, J and Seidel, M and Sommer, D and Franz-Wachtel, M and Barletta, F and Heumos, S and Czemmel, S and Kabashi, E and Ludolph, A and Boeckers, TM and Henstridge, CM and Catanese, A}, title = {Integrative proteomics highlight presynaptic alterations and c-Jun misactivation as convergent pathomechanisms in ALS.}, journal = {Acta neuropathologica}, volume = {146}, number = {3}, pages = {451-475}, pmid = {37488208}, issn = {1432-0533}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/pathology ; *Neurodegenerative Diseases/pathology ; Proteomics ; Superoxide Dismutase-1/genetics ; Motor Neurons/metabolism ; }, abstract = {Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease mainly affecting upper and lower motoneurons. Several functionally heterogeneous genes have been associated with the familial form of this disorder (fALS), depicting an extremely complex pathogenic landscape. This heterogeneity has limited the identification of an effective therapy, and this bleak prognosis will only improve with a greater understanding of convergent disease mechanisms. Recent evidence from human post-mortem material and diverse model systems has highlighted the synapse as a crucial structure actively involved in disease progression, suggesting that synaptic aberrations might represent a shared pathological feature across the ALS spectrum. To test this hypothesis, we performed the first comprehensive analysis of the synaptic proteome from post-mortem spinal cord and human iPSC-derived motoneurons carrying mutations in the major ALS genes. This integrated approach highlighted perturbations in the molecular machinery controlling vesicle release as a shared pathomechanism in ALS. Mechanistically, phosphoproteomic analysis linked the presynaptic vesicular phenotype to an accumulation of cytotoxic protein aggregates and to the pro-apoptotic activation of the transcription factor c-Jun, providing detailed insights into the shared pathobiochemistry in ALS. Notably, sub-chronic treatment of our iPSC-derived motoneurons with the fatty acid docosahexaenoic acid exerted a neuroprotective effect by efficiently rescuing the alterations revealed by our multidisciplinary approach. Together, this study provides strong evidence for the central and convergent role played by the synaptic microenvironment within the ALS spinal cord and highlights a potential therapeutic target that counteracts degeneration in a heterogeneous cohort of human motoneuron cultures.}, } @article {pmid37488110, year = {2023}, author = {Huang, LY and Ou, YN and Yang, YX and Wang, ZT and Tan, L and Yu, JT}, title = {Associations of cardiovascular risk factors and lifestyle behaviors with neurodegenerative disease: a Mendelian randomization study.}, journal = {Translational psychiatry}, volume = {13}, number = {1}, pages = {267}, pmid = {37488110}, issn = {2158-3188}, mesh = {Humans ; Risk Factors ; *Neurodegenerative Diseases/epidemiology/genetics ; Mendelian Randomization Analysis ; Genome-Wide Association Study ; *Amyotrophic Lateral Sclerosis/genetics ; *Cardiovascular Diseases/epidemiology/genetics ; Heart Disease Risk Factors ; Polymorphism, Single Nucleotide ; Life Style ; }, abstract = {Previous observational studies reported that midlife clustering of cardiovascular risk factors and lifestyle behaviors were associated with neurodegenerative disease; however, these findings might be biased by confounding and reverse causality. This study aimed to investigate the causal associations of cardiovascular risk factors and lifestyle behaviors with neurodegenerative disease, using the two-sample Mendelian randomization design. Genetic variants for the modifiable risk factors and neurodegenerative disease were extracted from large-scale genome-wide association studies. The inverse-variance weighted method was used as the main analysis method, and MR-Egger regression and leave-one-out analyses were performed to identify potential violations. Genetically predicted diastolic blood pressure (DBP: OR per 1 mmHg, 0.990 [0.979-1.000]), body mass index (BMI: OR per 1 SD, 0.880 [0.825-0.939]), and educational level (OR per 1 SD, 0.698 [0.602-0.810]) were associated with lower risk of late-onset Alzheimer's disease (LOAD), while genetically predicted low-density lipoprotein (LDL: OR per 1 SD, 1.302 [1.066-1.590]) might increase LOAD risk. Genetically predicted exposures (including LDL and BMI) applied to familial AD showed the same effect. The association of LDL was also found with Amyotrophic lateral sclerosis (ALS) (LDL: OR per 1 SD, 1.180 [1.080-1.289]). This MR analysis showed that LDL, BMI, BP, and educational level were causally related to AD; a significant association between LDL and ALS risk, as well as the potential effect of sleep duration on PD risk, were also revealed. Targeting these modifiable factors was a promising strategy of neurodegenerative disease prevention.}, } @article {pmid37488055, year = {2023}, author = {Letko, A and Brülisauer, F and Häfliger, IM and Corr, E and Scholes, S and Drögemüller, C}, title = {Loss-of-function variant in the ovine TMCO6 gene in North Country Cheviot sheep with motor neuron disease.}, journal = {Genomics}, volume = {115}, number = {5}, pages = {110689}, doi = {10.1016/j.ygeno.2023.110689}, pmid = {37488055}, issn = {1089-8646}, abstract = {In North Country Cheviot lambs with early-onset progressive ataxia and motor neuron degeneration, whole-genome sequencing identified a homozygous loss-of-function variant in the ovine transmembrane and coiled-coil domains (TMCO6) gene. The familial recessive form of motor neuron disease in sheep is due to a pathogenic 4 bp deletion leading to a 50% protein truncation that is assumed to result in the absence of a functional TMCO6. This uncharacterised protein is proposed to interact with ubiquilin 1 which is associated with Alzheimer's disease, whereas sporadic forms of amyotrophic lateral sclerosis are caused by variants in UBQLN2. Our findings provide a first spontaneous animal model for TMCO6, which could have implications in the studies of other comparative neurodegenerative diseases. In addition, these results will allow the design of a genetic test to prevent the occurrence of this fatal disease in the affected sheep population.}, } @article {pmid37486495, year = {2023}, author = {Papikinos, T and Krokidis, MG and Vrahatis, A and Vlamos, P and Exarchos, TP}, title = {Signature-Based Computational Drug Repurposing for Amyotrophic Lateral Sclerosis.}, journal = {Advances in experimental medicine and biology}, volume = {1424}, number = {}, pages = {201-211}, pmid = {37486495}, issn = {0065-2598}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy/genetics/metabolism ; Drug Repositioning ; *Neurodegenerative Diseases ; Transcriptome ; Motor Neurons/metabolism ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a late-onset fatal neurodegenerative disease characterized by progressive loss of the upper and lower motor neurons. There are currently limited approved drugs for the disorder, and for this reason the strategy of repositioning already approved therapeutics could exhibit a successful outcome. Herein, we used CMAP and L1000CDS[2] databases which include gene expression profiles datasets (genomic signatures) to identify potent compounds and classes of compounds which reverse disease's signature which could in turn reverse its phenotype. ALS signature was obtained by comparing gene expression of muscle biopsy specimens between diseased and healthy individuals. Statistical analysis was conducted to explore differentially transcripts in patients' samples. Then, the list of upregulated and downregulated genes was used to query both databases in order to determine molecules which downregulate the genes which are upregulated by ALS and vice versa. These compounds, based on their chemical structure along with known treatments, were clustered to reveal drugs with novel and potentially more effective mode of action with most of them predicted to affect pathways heavily involved in ALS. This evidence suggests that these compounds are strong candidates for moving to the next phase of the drug repurposing pipeline which is in vitro and in vivo experimental evaluation.}, } @article {pmid37486108, year = {2023}, author = {Malmström, N and Jakobsson Larsson, B and Nilsson, S and Öhlén, J and Nygren, I and Andersen, PM and Ozanne, A}, title = {Living with a parent with ALS - adolescents' need for professional support from the adolescents' and the parents' perspectives.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {}, number = {}, pages = {1-9}, doi = {10.1080/21678421.2023.2228348}, pmid = {37486108}, issn = {2167-9223}, abstract = {AIM: The aim of the study was to qualitatively investigate the adolescents' need for professional support when a parent has amyotrophic lateral sclerosis (ALS) - from the adolescents' and the parents' perspectives.

METHODS: A total of 37 individual semi-structured single interviews with 18 families were conducted, including 11 adolescents aged 8-25 and 26 parents, 13 with ALS and 13 co-parents. Data was analysed using qualitative content analysis.

RESULTS: Both adolescents and parents described the adolescents as needing professional support but found it difficult to articulate this need. However, the results indicate that the adolescents needed help in bringing manageability into their lives due to the uncertainty of living with the illness in the family. It was therefore essential to ensure that the adolescents were not forgotten in the disease context and that their needs for being involved as well as for obtaining information and understanding, was addressed. The importance of offering the adolescents support early was emphasized, but also of actively helping the families to master challenges in their everyday life. Support adapted to each family's unique situation and preferences was desired, as the adolescents' need for support seemed to be individual, disease-dependent and varied during different phases.

CONCLUSION: Given the adolescents' need for information and understanding, healthcare professionals must actively work to reach the adolescents as early as possible. It is crucial to ensure that the adolescents are given the opportunity to be involved based on their own conditions, as well as to support the families to strengthen their communication.}, } @article {pmid37485983, year = {2023}, author = {van Kessel, CS and Waller, J and Steffens, D and Lee, PJ and Austin, KKS and Stalley, PD and Solomon, MJ}, title = {Improving Surgical Outcomes in Pelvic Exenteration Surgery: Comparison of Prone Sacrectomy With Anterior Cortical Sacrectomy Techniques.}, journal = {Annals of surgery}, volume = {278}, number = {6}, pages = {945-953}, doi = {10.1097/SLA.0000000000006040}, pmid = {37485983}, issn = {1528-1140}, mesh = {Humans ; *Pelvic Exenteration/methods ; *Rectal Neoplasms/surgery/pathology ; Retrospective Studies ; Sacrum/surgery/pathology ; Treatment Outcome ; }, abstract = {OBJECTIVE: To assess the effect of changing our sacrectomy approach from prone to anterior on surgical and oncological outcomes.

BACKGROUND: In patients with advanced pelvic malignancy involving the sacrum, pelvic exenteration (PE) with en-bloc sacrectomy is the only potential curative option but morbidity is high. Over time sacrectomy techniques have evolved from prone sacrectomy (PS) to abdominolithotomy sacrectomy (ALS, ≤S3) and high anterior cortical sacrectomy (HACS, >S3) to optimize surgical outcomes.

METHODS: A retrospective, single institution analysis of prospectively collected data for patients undergoing PE with en-bloc sacrectomy between 1994 and 2021 was performed.

RESULTS: A total of 363 patients were identified and divided into PS (n=77, 21.2%), ALS (n=247, 68.0%), and HACS (n=39, 10.7%). Indications were: locally advanced (n=92) or recurrent (n=177) rectal cancer, primary other (n=31), recurrent other (n=60), and benign disease (n=3). PS resulted in longer operating time (P <0.01) and more blood loss (P <0.01). Patients with HACS had more major nerve (87.2%) and vascular (25.6%) resections (P <0.01). Vertical rectus abdominis myocutaneous flap repair was less common following HACS (7.7%) than ALS (25.5%) and PS (27.3%) (P =0.040). R0 rate was 80.8%, 65.8%, and 76.9% following ALS, PS, and HACS, respectively (P =0.024). Wound-related complications and re-operations were significantly reduced following ALS and HACS compared with PS.

CONCLUSIONS: Changing our practice from PS to an anterior approach with ALS or HAS has been safe and improved overall surgical and perioperative outcomes, while maintaining good oncological outcomes. Given the improved perioperative and surgical outcomes, it would be important for surgeons to learn and adopt the anterior sacrectomy approaches.}, } @article {pmid37484758, year = {2023}, author = {Chen, TY and Hsu, CW and Chang, YP and Wang, MT and Wu, YJ and Wang, CH and Wang, KY and Chu, TH and Lee, YK}, title = {Percutaneous transhepatic duodenal drainage is good option for afferent loop syndrome for obstructive colorectal cancer patient with history of Billroth's operation II: A case report of a rare postoperative complication.}, journal = {Clinical case reports}, volume = {11}, number = {7}, pages = {e7725}, pmid = {37484758}, issn = {2050-0904}, abstract = {KEY CLINICAL MESSAGE: Temporal percutaneous transhepatic duodenum drainage (PTDD) seems to be effective in the treatment of postoperative afferent loop syndrome (ALS) following transverse loop colostomy for obstructive colorectal cancer.

ABSTRACT: Management of obstructive colorectal cancer still remains a challenge. There are various options with different risks of mortality and mobility for obstructive colorectal cancer. A rare unexpected postoperative ALS following a low anterior resection and transverse loop colostomy for obstructive colorectal cancer is presented in this report. A 64-year-old man had the acute ALS had been noted 10 days after transverse loop colostomy. An option was temporal PTDD treatment in the patient with history of Billroth's operation II for upper gastrointestinal bleeding 30 years ago. Acute ALS was treated by temporal PTDD. The drainage tube for PTDD was not removed until closure of the transverse colostomy 2 months later. The patient recovered uneventfully. Acute ALS after transverse loop colostomy for obstructive colorectal cancer is rare and has never been reported in the literature. The mechanism of acute ALS after construction of a loop colostomy and the treatment strategy of PTDD for acute ALS is presented.}, } @article {pmid37484552, year = {2023}, author = {}, title = {Correction to: Bulbar onset amyotrophic lateral sclerosis with more evident symptoms in the left hemibody: a case report.}, journal = {Oxford medical case reports}, volume = {2023}, number = {7}, pages = {omad077}, doi = {10.1093/omcr/omad077}, pmid = {37484552}, issn = {2053-8855}, abstract = {[This corrects the article DOI: 10.1093/omcr/omad045.].}, } @article {pmid37483353, year = {2023}, author = {Shi, Y and Zhao, Y and Lu, L and Gao, Q and Yu, D and Sun, M}, title = {CRISPR/Cas9: implication for modeling and therapy of amyotrophic lateral sclerosis.}, journal = {Frontiers in neuroscience}, volume = {17}, number = {}, pages = {1223777}, pmid = {37483353}, issn = {1662-4548}, abstract = {Amyotrophic lateral sclerosis (ALS) is a deadly neurological disease with a complicated and variable pathophysiology yet to be fully understood. There is currently no effective treatment available to either slow or terminate it. However, recent advances in ALS genomics have linked genes to phenotypes, encouraging the creation of novel therapeutic approaches and giving researchers more tools to create efficient animal models. Genetically engineered rodent models replicating ALS disease pathology have a high predictive value for translational research. This review addresses the history of the evolution of gene editing tools, the most recent ALS disease models, and the application of CRISPR/Cas9 against ALS disease.}, } @article {pmid37482930, year = {2023}, author = {Grassano, M and Manera, U and De Marchi, F and Cugnasco, P and Matteoni, E and Daviddi, M and Solero, L and Bombaci, A and Palumbo, F and Vasta, R and Canosa, A and Salamone, P and Fuda, G and Casale, F and Mazzini, L and Calvo, A and Moglia, C and Chiò, A}, title = {The role of peripheral immunity in ALS: a population-based study.}, journal = {Annals of clinical and translational neurology}, volume = {10}, number = {9}, pages = {1623-1632}, pmid = {37482930}, issn = {2328-9503}, mesh = {Humans ; Female ; *Amyotrophic Lateral Sclerosis ; Lymphocytes ; Blood Cell Count ; Leukocytes ; Inflammation ; }, abstract = {BACKGROUND: Systemic inflammation has been proposed as a relevant mechanism in amyotrophic lateral sclerosis (ALS). Still, comprehensive data on ALS patients' innate and adaptive immune responses and their effect on the clinical phenotype are lacking. Here, we investigate systemic immunity in a population-based ALS cohort using readily available hematological indexes.

METHODS: We collected clinical data and the complete blood count (CBC) at diagnosis in ALS patients from the Piemonte and Valle d'Aosta Register for ALS (PARALS) from 2007 to 2019. Leukocytes populations, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic-immune-inflammation index (SII), and lymphocyte-to-monocyte ratio (LMR) were derived from CBC. All variables were analyzed for association with clinical features in the entire cohort and then in sex- and age-based subgroups.

RESULTS: Neutrophils (P = 0.001) and markers of increased innate immunity (NLR, P = 0.008 and SII, P = 0.006) were associated with a faster disease progression. Similarly, elevated innate immunity correlated with worse pulmonary function and shorter survival. The prognosis in women also correlated with low lymphocytes (P = 0.045) and a decreased LMR (P = 0.013). ALS patients with cognitive impairment exhibited lower monocytes (P = 0.0415).

CONCLUSIONS AND RELEVANCE: The dysregulation of the systemic immune system plays a multifaceted role in ALS. More specifically, an elevated innate immune response is associated with faster progression and reduced survival. Conversely, ALS patients with cognitive impairment showed a reduction in monocyte count. Additionally, immune response varied according to sex and age, thus suggesting that involved immune pathways are patient specific. Further studies will help translate those findings into clinical practice or targeted treatments.}, } @article {pmid37482646, year = {2024}, author = {Liu, K and Guo, Q and Ding, Y and Luo, L and Huang, J and Zhang, Q}, title = {Alterations in nasal microbiota of patients with amyotrophic lateral sclerosis.}, journal = {Chinese medical journal}, volume = {137}, number = {2}, pages = {162-171}, pmid = {37482646}, issn = {2542-5641}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/microbiology ; Feces/microbiology ; *Microbiota/genetics ; *Gastrointestinal Microbiome/genetics ; Bacteria/genetics ; RNA, Ribosomal, 16S/genetics ; }, abstract = {BACKGROUND: Links between alterations in gut microbiota composition and amyotrophic lateral sclerosis (ALS) have previously been reported. This study aimed to examine the microbiota in the nasal cavity of ALS.

METHODS: Sixty-six ALS patients and 40 healthy caregivers who live in close proximity with patients were enrolled. High throughput metagenomic sequencing of the 16S ribosomal deoxyribonucleic acid (rDNA) gene V3-V4 region of nasal microbiota was used to characterize the alpha and beta diversity and relative abundance of bacterial taxa, predict function, and conduct correlation analysis between specific taxa and clinical features.

RESULTS: The nasal microbiome of ALS patients showed lower alpha diversity than that of corresponding healthy family members. Genera Gaiella , Sphingomonas , Polaribacter _1, Lachnospiraceae _NK4A136_group, Klebsiella , and Alistipes were differentially enriched in ALS patients compared to controls. Nasal microbiota composition in ALS patients significantly differed from that in healthy subjects (unweighted UniFrac P = 0.001), while Linear discriminant analysis Effect Size (LEfSe) analysis indicated that Bacteroidetes and Firmicutes dominated healthy nasal communities at the phylum level, whereas Actinobacteria was the predominant phylum and Thermoleophilia was the predominant class in ALS patients. Genus Faecalibacterium and Alistipes were positively correlated with ALS functional rating scale revised (ALSFRS-R; rs = 0.349, P = 0.020 and rs = 0.393, P = 0.008), while Prevotella -9 and Bacteroides operational taxonomic units (OTUs) were positively associated with lung function (FVC) in ALS patients (rs = 0.304, P = 0.045, and rs = 0.300, P = 0.048, respectively). Prevotella -1 was positively correlated with white blood cell counts (WBC, rs = 0.347, P = 0.021), neutrophil percentage (Neu%, rs = 0.428, P = 0.004), and neutrophil-to-lymphocyte ratio (NLR, rs = 0.411, P = 0.006), but negatively correlated with lymphocyte percentage (Lym%, rs = -0.408, P = 0.006). In contrast, Streptococcus was negatively associated with Neu% (rs = -0.445, P = 0.003) and NLR (rs = -0.436, P = 0.003), while positively associated with Lym% (rs = 0.437, P = 0.003). No significant differences in nasal microbiota richness and evenness were detected among the severe and mild ALS patients.

CONCLUSIONS: ALS is accompanied by altered nasal microbial community composition and diversity. The findings presented here highlight the need to understand how dysbiosis of nasal microbiota may contribute to the development of ALS.}, } @article {pmid37481656, year = {2023}, author = {Mohovic, N and Peradinovic, J and Markovinovic, A and Cimbro, R and Minic, Z and Dominovic, M and Jakovac, H and Nimac, J and Rogelj, B and Munitic, I}, title = {Neuroimmune characterization of optineurin insufficiency mouse model during ageing.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {11840}, pmid = {37481656}, issn = {2045-2322}, mesh = {Male ; Mice ; Animals ; *Amyotrophic Lateral Sclerosis/metabolism ; *Frontotemporal Dementia ; Polyubiquitin/genetics ; Cell Cycle Proteins/metabolism ; Signal Transduction ; Mutation ; Aging ; }, abstract = {Optineurin is a multifunctional polyubiquitin-binding protein implicated in inflammatory signalling. Optineurin mutations are associated with amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), neurodegenerative diseases characterised by neuronal loss, neuroinflammation, and peripheral immune disbalance. However, the pathogenic role of optineurin mutations is unclear. We previously observed no phenotype in the unmanipulated young optineurin insufficiency mice (Optn[470T]), designed to mimic ALS/FTD-linked truncations deficient in polyubiquitin binding. The purpose of this study was to investigate whether ageing would trigger neurodegeneration. We performed a neurological, neuropathological, and immunological characterization of ageing wild-type (WT) and Optn[470T] mice. No motor or cognitive differences were detected between the genotypes. Neuropathological analyses demonstrated signs of ageing including lipofuscin accumulation and microglial activation in WT mice. However, this was not worsened in Optn[470T] mice, and they did not exhibit TAR DNA-binding protein 43 (TDP-43) aggregation or neuronal loss. Spleen immunophenotyping uncovered T cell immunosenescence at two years but without notable differences between the WT and Optn[470T] mice. Conventional dendritic cells (cDC) and macrophages exhibited increased expression of activation markers in two-year-old Optn[470T] males but not females, although the numbers of innate immune cells were similar between genotypes. Altogether, a combination of optineurin insufficiency and ageing did not induce ALS/FTD-like immune imbalance and neuropathology in mice.}, } @article {pmid37481642, year = {2023}, author = {Yang, R and Yang, B and Liu, W and Tan, C and Chen, H and Wang, X}, title = {Emerging role of non-coding RNAs in neuroinflammation mediated by microglia and astrocytes.}, journal = {Journal of neuroinflammation}, volume = {20}, number = {1}, pages = {173}, pmid = {37481642}, issn = {1742-2094}, support = {32102749//National Natural Science Foundation of China/ ; 32122086//National Natural Science Foundation of China/ ; 2022M721277//China Postdoctoral Science Foundation/ ; 2021YFD1800800//National Key Research and Development Program of China/ ; 2021CFA016//Natural Science Foundation of Hubei Province/ ; 2662023PY005//Fundamental Research Funds for the Central Universities/ ; }, mesh = {Humans ; Astrocytes ; Microglia ; Neuroinflammatory Diseases ; *RNA, Long Noncoding/genetics ; *MicroRNAs ; }, abstract = {Neuroinflammation has been implicated in the initiation and progression of several central nervous system (CNS) disorders, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis, ischemic stroke, traumatic brain injury, spinal cord injury, viral encephalitis, and bacterial encephalitis. Microglia and astrocytes are essential in neural development, maintenance of synaptic connections, and homeostasis in a healthy brain. The activation of astrocytes and microglia is a defense mechanism of the brain against damaged tissues and harmful pathogens. However, their activation triggers neuroinflammation, which can exacerbate or induce CNS injury. Non-coding RNAs (ncRNAs) are functional RNA molecules that lack coding capabilities but can actively regulate mRNA expression and function through various mechanisms. ncRNAs are highly expressed in astrocytes and microglia and are potential mediators of neuroinflammation. We reviewed the recent research progress on the role of miRNAs, lncRNAs, and circRNAs in regulating neuroinflammation in various CNS diseases. Understanding how these ncRNAs affect neuroinflammation will provide important therapeutic insights for preventing and managing CNS dysfunction.}, } @article {pmid37481159, year = {2023}, author = {Sharma, K and Banerjee, S and Savran, D and Rajes, C and Wiese, S and Girdhar, A and Schwierz, N and Lee, C and Shorter, J and Schmidt, M and Guo, L and Fändrich, M}, title = {Cryo-EM Structure of the Full-length hnRNPA1 Amyloid Fibril.}, journal = {Journal of molecular biology}, volume = {435}, number = {18}, pages = {168211}, pmid = {37481159}, issn = {1089-8638}, support = {R01 GM099836/GM/NIGMS NIH HHS/United States ; R35 GM138109/GM/NIGMS NIH HHS/United States ; /CRUK_/Cancer Research UK/United Kingdom ; }, mesh = {*Amyloid/chemistry ; Cryoelectron Microscopy/methods ; *Heterogeneous Nuclear Ribonucleoprotein A1/chemistry ; Mutation ; Prions/chemistry ; Protein Domains ; }, abstract = {Heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) is a multifunctional RNA-binding protein that is associated with neurodegenerative diseases, such as amyotrophic lateral sclerosis and multisystem proteinopathy. In this study, we have used cryo-electron microscopy to investigate the three-dimensional structure of amyloid fibrils from full-length hnRNPA1 protein. We find that the fibril core is formed by a 45-residue segment of the prion-like low-complexity domain of the protein, whereas the remaining parts of the protein (275 residues) form a fuzzy coat around the fibril core. The fibril consists of two fibril protein stacks that are arranged into a pseudo-21 screw symmetry. The ordered core harbors several of the positions that are known to be affected by disease-associated mutations, but does not encompass the most aggregation-prone segments of the protein. These data indicate that the structures of amyloid fibrils from full-length proteins may be more complex than anticipated by current theories on protein misfolding.}, } @article {pmid37480846, year = {2023}, author = {Ziff, OJ and Harley, J and Wang, Y and Neeves, J and Tyzack, G and Ibrahim, F and Skehel, M and Chakrabarti, AM and Kelly, G and Patani, R}, title = {Nucleocytoplasmic mRNA redistribution accompanies RNA binding protein mislocalization in ALS motor neurons and is restored by VCP ATPase inhibition.}, journal = {Neuron}, volume = {111}, number = {19}, pages = {3011-3027.e7}, doi = {10.1016/j.neuron.2023.06.019}, pmid = {37480846}, issn = {1097-4199}, support = {FC010110/WT_/Wellcome Trust/United Kingdom ; MR/S006591/1/MRC_/Medical Research Council/United Kingdom ; FC010110/MRC_/Medical Research Council/United Kingdom ; FC010110/CRUK_/Cancer Research UK/United Kingdom ; MC_PC_19038/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/metabolism ; Adenosine Triphosphatases/genetics/metabolism ; RNA, Messenger/metabolism ; Motor Neurons/metabolism ; RNA-Binding Proteins/metabolism ; Valosin Containing Protein/genetics ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is characterized by nucleocytoplasmic mislocalization of the RNA-binding protein (RBP) TDP-43. However, emerging evidence suggests more widespread mRNA and protein mislocalization. Here, we employed nucleocytoplasmic fractionation, RNA sequencing, and mass spectrometry to investigate the localization of mRNA and protein in induced pluripotent stem cell-derived motor neurons (iPSMNs) from ALS patients with TARDBP and VCP mutations. ALS mutant iPSMNs exhibited extensive nucleocytoplasmic mRNA redistribution, RBP mislocalization, and splicing alterations. Mislocalized proteins exhibited a greater affinity for redistributed transcripts, suggesting a link between RBP mislocalization and mRNA redistribution. Notably, treatment with ML240, a VCP ATPase inhibitor, partially restored mRNA and protein localization in ALS mutant iPSMNs. ML240 induced changes in the VCP interactome and lysosomal localization and reduced oxidative stress and DNA damage. These findings emphasize the link between RBP mislocalization and mRNA redistribution in ALS motor neurons and highlight the therapeutic potential of VCP inhibition.}, } @article {pmid37480213, year = {2023}, author = {Suddull, HJ and Rosa-Fernandes, L and Lee, A}, title = {How can proteomics help solve the lack of biomarkers to aid in the early diagnosis of motor neuron disease (MND)?.}, journal = {Expert review of proteomics}, volume = {20}, number = {7-9}, pages = {121-123}, doi = {10.1080/14789450.2023.2240513}, pmid = {37480213}, issn = {1744-8387}, } @article {pmid37478793, year = {2023}, author = {Fournier, JE and Mak, G and Gordon, K and Glogauer, J and Fareez, F and Provias, J and Tarnopolsky, MA and Lu, JQ}, title = {Cylindrical spirals and other concentric structures of skeletal muscle in patients with neurological diseases.}, journal = {Journal of the neurological sciences}, volume = {451}, number = {}, pages = {120734}, doi = {10.1016/j.jns.2023.120734}, pmid = {37478793}, issn = {1878-5883}, mesh = {Adult ; Humans ; Infant ; Muscle, Skeletal/pathology ; *Muscular Diseases/pathology ; *Neuromuscular Diseases ; *Huntington Disease/pathology ; Muscular Atrophy/pathology ; }, abstract = {Cylindrical spirals (CSs) are ultrastructurally distinct, intracytoplasmic inclusions characterized by concentrically wrapped lamellae, which are rarely found in skeletal muscle biopsies on electron microscopy (EM). CSs are often confused with other EM concentric structures including concentric laminated bodies and mitochondrial concentric cristae (MCC), due to similarities in these ultrastructures. In this study, we found CSs in 9 muscle biopsies from 9 patients, accounting for 0.5% of the biopsies examined routinely by EM. The frequency of CSs in these muscles varied from sparse and segregated to focally frequent and aggregated. CS-associated features included muscle fiber denervation atrophy in all 9 cases, fiber type grouping in 7/8 cases, tubular aggregates in 3/9 cases, and MCC in 2/9 cases. We also compared the concentric structures and highlighted their differences to distinguish CSs from other similar structures. Clinically, 8 out of 9 patients were adults aged 41-74 years and only one patient was 17 month-old. CSs were associated with several neurological diseases including Huntington's disease, amyotrophic lateral sclerosis, Mitochondrial Encephalopathy, Lactic Acidosis, and Stroke-like episodes, and other complex neurological disorders with neuropathy/encephalopathy, as well as anti-MDA5+ dermatomyositis. Eight of nine patients had genetic findings such as trinucleotide repeat expansion of huntingtin gene, ALS2 variant, MT-TL1 m.3243A > G mutation, and PMP 22 gene deletion. These results suggest that CSs may be highly variable in frequency and likely are under-reported/under-detected; they may be associated with neurogenic myopathy or central/peripheral nervous system disorders including some genetic neurological/neuromuscular diseases. Our findings of more CS-associated neurological diseases and an association of CSs with muscle neurogenic features may contribute to a better understanding of the clinico-pathological significance of CSs.}, } @article {pmid37477391, year = {2023}, author = {Alix, JJP and Plesia, M and Shaw, PJ and Mead, RJ and Day, JCC}, title = {Combining electromyography and Raman spectroscopy: optical EMG.}, journal = {Muscle & nerve}, volume = {68}, number = {4}, pages = {464-470}, pmid = {37477391}, issn = {1097-4598}, support = {MC_PC_15034/MRC_/Medical Research Council/United Kingdom ; NF-SI-0617-10077/DH_/Department of Health/United Kingdom ; IS-BRC-1215-20017/DH_/Department of Health/United Kingdom ; }, mesh = {Mice ; Animals ; Electromyography ; Superoxide Dismutase-1/genetics ; *Spectrum Analysis, Raman ; Muscle, Skeletal ; Mice, Transgenic ; *Amyotrophic Lateral Sclerosis/diagnosis/genetics ; Disease Models, Animal ; Superoxide Dismutase ; }, abstract = {INTRODUCTION/AIMS: Electromyography (EMG) remains a key component of the diagnostic work-up for suspected neuromuscular disease, but it does not provide insight into the molecular composition of muscle which can provide diagnostic information. Raman spectroscopy is an emerging neuromuscular biomarker capable of generating highly specific, molecular fingerprints of tissue. Here, we present "optical EMG," a combination of EMG and Raman spectroscopy, achieved using a single needle.

METHODS: An optical EMG needle was created to collect electrophysiological and Raman spectroscopic data during a single insertion. We tested functionality with in vivo recordings in the SOD1[G93A] mouse model of amyotrophic lateral sclerosis (ALS), using both transgenic (n = 10) and non-transgenic (NTg, n = 7) mice. Under anesthesia, compound muscle action potentials (CMAPs), spontaneous EMG activity and Raman spectra were recorded from both gastrocnemius muscles with the optical EMG needle. Standard concentric EMG needle recordings were also undertaken. Electrophysiological data were analyzed with standard univariate statistics, Raman data with both univariate and multivariate analyses.

RESULTS: A significant difference in CMAP amplitude was observed between SOD1[G93A] and NTg mice with optical EMG and standard concentric needles (p = .015 and p = .011, respectively). Spontaneous EMG activity (positive sharp waves) was detected in transgenic SOD1[G93A] mice only. Raman spectra demonstrated peaks associated with key muscle components. Significant differences in molecular composition between SOD1[G93A] and NTg muscle were identified through the Raman spectra.

DISCUSSION: Optical EMG can provide standard electrophysiological data and molecular Raman data during a single needle insertion and represents a potential biomarker for neuromuscular disease.}, } @article {pmid37476298, year = {2023}, author = {Nitu, NS and Sultana, SZ and Haq, A and Sumi, SA and Bose, SK and Sinha, S and Kumar, S and Haque, M}, title = {Histological Study on the Thickness of Gray Matter at the Summit and Bottom of Folium in Different Age Groups of Bangladeshi People.}, journal = {Cureus}, volume = {15}, number = {7}, pages = {e42103}, pmid = {37476298}, issn = {2168-8184}, abstract = {Context The cerebellum is a part of the hindbrain and consists of cortical gray matter (GM) at the surface and a medullary core of white matter (WM). The GM contains a cell body of neurons that helps process and transmit any command type through nerve fibers found in the WM. The main functions of GM in the central nervous system empower persons to control motor activity, recollection, and passion. So, this research aims to assess the thickness of GM at the summit and bottom of folia by histologically studying the cerebellum cortex. Methods The collection of data was a descriptive type of cross-sectional study. The method was the purposive type. This study was conducted from August 2016 to March 2017, and the research was carried out at Mymensingh Medical College's Department of Anatomy, Bangladesh. Specimens containing cerebellum were preserved from Bangladeshi cadavers according to sexes and ages ranging in years. We chose fresh specimens from people who died within the last 12 hours and preserved them in 10% formol saline. The size of the tissue that was collected for the histological study was not more than 2 cm[2] and not more than 4-5 mm thick. Then the tissue was placed in 10% formol saline. This fluid was used for quick fixation and partial dehydration of the tissue. After dehydration, each tissue segment is processed for infiltration and embedding separately. Every section was stained with hematoxylin and eosin stain (H&E) before being coated with dibutyl phthalate polystyrene xylene (DPX) coverslips on slides. Result The mean (±SD) thickness of GM at the summit of folium was 886.2±29.7µm in Group A, 925.2±25.9µm in Group B, 912.7±22.3µm in Group C, and 839.9±40.7µm in Group D. Mean (±SD) GM thickness at the bottom of the fissure was 395.6±12.2 µm, 403.9±26.0µm, 380.4±23.4 µm, and 375.8±28.8 µm in Groups A, B, C, and D respectively. Conclusion The thickness of the cortex is an essential factor in the normal development process, and it was similar in the current study. Normal aging, Alzheimer's disease, and other dementias cause reduced GM which makes the cortical sheet thin. Huntington's disease, corticobasal degeneration, amyotrophic lateral sclerosis, and schizophrenia are all examples of neurological disorders. Cortical thinning is typically locally localized, and the progression of atrophy can thus disclose much about a disease's history and causal variables. The present study correspondingly found that GM was reduced after the age of 50 years onward. Furthermore, longitudinal investigations of cortical atrophy have the potential to be extremely useful in measuring the efficacy of a wide range of treatments.}, } @article {pmid37475885, year = {2023}, author = {Acosta-Galeana, I and Hernández-Martínez, R and Reyes-Cruz, T and Chiquete, E and Aceves-Buendia, JJ}, title = {RNA-binding proteins as a common ground for neurodegeneration and inflammation in amyotrophic lateral sclerosis and multiple sclerosis.}, journal = {Frontiers in molecular neuroscience}, volume = {16}, number = {}, pages = {1193636}, pmid = {37475885}, issn = {1662-5099}, abstract = {The neurodegenerative and inflammatory illnesses of amyotrophic lateral sclerosis and multiple sclerosis were once thought to be completely distinct entities that did not share any remarkable features, but new research is beginning to reveal more information about their similarities and differences. Here, we review some of the pathophysiological features of both diseases and their experimental models: RNA-binding proteins, energy balance, protein transportation, and protein degradation at the molecular level. We make a thorough analysis on TDP-43 and hnRNP A1 dysfunction, as a possible common ground in both pathologies, establishing a potential link between neurodegeneration and pathological immunity. Furthermore, we highlight the putative variations that diverge from a common ground in an atemporal course that proposes three phases for all relevant molecular events.}, } @article {pmid37475056, year = {2023}, author = {Yang, S and Park, JH and Lu, HC}, title = {Axonal energy metabolism, and the effects in aging and neurodegenerative diseases.}, journal = {Molecular neurodegeneration}, volume = {18}, number = {1}, pages = {49}, pmid = {37475056}, issn = {1750-1326}, support = {R01 NS086794/NS/NINDS NIH HHS/United States ; NS086794/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Humans ; *Neurodegenerative Diseases/metabolism ; NAD/metabolism ; Aging/metabolism ; Axons/metabolism ; Energy Metabolism ; Glucose/metabolism ; }, abstract = {Human studies consistently identify bioenergetic maladaptations in brains upon aging and neurodegenerative disorders of aging (NDAs), such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and Amyotrophic lateral sclerosis. Glucose is the major brain fuel and glucose hypometabolism has been observed in brain regions vulnerable to aging and NDAs. Many neurodegenerative susceptible regions are in the topological central hub of the brain connectome, linked by densely interconnected long-range axons. Axons, key components of the connectome, have high metabolic needs to support neurotransmission and other essential activities. Long-range axons are particularly vulnerable to injury, neurotoxin exposure, protein stress, lysosomal dysfunction, etc. Axonopathy is often an early sign of neurodegeneration. Recent studies ascribe axonal maintenance failures to local bioenergetic dysregulation. With this review, we aim to stimulate research in exploring metabolically oriented neuroprotection strategies to enhance or normalize bioenergetics in NDA models. Here we start by summarizing evidence from human patients and animal models to reveal the correlation between glucose hypometabolism and connectomic disintegration upon aging/NDAs. To encourage mechanistic investigations on how axonal bioenergetic dysregulation occurs during aging/NDAs, we first review the current literature on axonal bioenergetics in distinct axonal subdomains: axon initial segments, myelinated axonal segments, and axonal arbors harboring pre-synaptic boutons. In each subdomain, we focus on the organization, activity-dependent regulation of the bioenergetic system, and external glial support. Second, we review the mechanisms regulating axonal nicotinamide adenine dinucleotide (NAD[+]) homeostasis, an essential molecule for energy metabolism processes, including NAD[+] biosynthetic, recycling, and consuming pathways. Third, we highlight the innate metabolic vulnerability of the brain connectome and discuss its perturbation during aging and NDAs. As axonal bioenergetic deficits are developing into NDAs, especially in asymptomatic phase, they are likely exaggerated further by impaired NAD[+] homeostasis, the high energetic cost of neural network hyperactivity, and glial pathology. Future research in interrogating the causal relationship between metabolic vulnerability, axonopathy, amyloid/tau pathology, and cognitive decline will provide fundamental knowledge for developing therapeutic interventions.}, } @article {pmid37474791, year = {2023}, author = {Li, D and Johmura, Y and Morimoto, S and Doi, M and Nakanishi, K and Ozawa, M and Tsunekawa, Y and Inoue-Yamauchi, A and Naruse, H and Matsukawa, T and Takeshita, Y and Suzuki, N and Aoki, M and Nishiyama, A and Zeng, X and Konishi, C and Suzuki, N and Nishiyama, A and Harris, AS and Morita, M and Yamaguchi, K and Furukawa, Y and Nakai, K and Tsuji, S and Yamazaki, S and Yamanashi, Y and Shimada, S and Okada, T and Okano, H and Toda, T and Nakanishi, M}, title = {LONRF2 is a protein quality control ubiquitin ligase whose deficiency causes late-onset neurological deficits.}, journal = {Nature aging}, volume = {3}, number = {8}, pages = {1001-1019}, pmid = {37474791}, issn = {2662-8465}, mesh = {Animals ; Mice ; DNA Helicases/metabolism ; DNA-Binding Proteins/genetics ; Ligases/metabolism ; *Motor Neurons/metabolism ; Poly-ADP-Ribose Binding Proteins/metabolism ; RNA Helicases/metabolism ; RNA Recognition Motif Proteins/metabolism ; *Ubiquitin/metabolism ; *Ubiquitin-Protein Ligases/genetics/metabolism ; }, abstract = {Protein misfolding is a major factor of neurodegenerative diseases. Post-mitotic neurons are highly susceptible to protein aggregates that are not diluted by mitosis. Therefore, post-mitotic cells may have a specific protein quality control system. Here, we show that LONRF2 is a bona fide protein quality control ubiquitin ligase induced in post-mitotic senescent cells. Under unperturbed conditions, LONRF2 is predominantly expressed in neurons. LONRF2 binds and ubiquitylates abnormally structured TDP-43 and hnRNP M1 and artificially misfolded proteins. Lonrf2[-/-] mice exhibit age-dependent TDP-43-mediated motor neuron (MN) degeneration and cerebellar ataxia. Mouse induced pluripotent stem cell-derived MNs lacking LONRF2 showed reduced survival, shortening of neurites and accumulation of pTDP-43 and G3BP1 after long-term culture. The shortening of neurites in MNs from patients with amyotrophic lateral sclerosis is rescued by ectopic expression of LONRF2. Our findings reveal that LONRF2 is a protein quality control ligase whose loss may contribute to MN degeneration and motor deficits.}, } @article {pmid37474587, year = {2023}, author = {Zilio, F and Gomez-Pilar, J and Chaudhary, U and Fogel, S and Fomina, T and Synofzik, M and Schöls, L and Cao, S and Zhang, J and Huang, Z and Birbaumer, N and Northoff, G}, title = {Altered brain dynamics index levels of arousal in complete locked-in syndrome.}, journal = {Communications biology}, volume = {6}, number = {1}, pages = {757}, pmid = {37474587}, issn = {2399-3642}, support = {//CIHR/Canada ; }, mesh = {Humans ; *Locked-In Syndrome ; Electroencephalography/methods ; Brain/physiology ; Wakefulness ; Biomarkers ; }, abstract = {Complete locked-in syndrome (CLIS) resulting from late-stage amyotrophic lateral sclerosis (ALS) is characterised by loss of motor function and eye movements. The absence of behavioural indicators of consciousness makes the search for neuronal correlates as possible biomarkers clinically and ethically urgent. EEG-based measures of brain dynamics such as power-law exponent (PLE) and Lempel-Ziv complexity (LZC) have been shown to have explanatory power for consciousness and may provide such neuronal indices for patients with CLIS. Here, we validated PLE and LZC (calculated in a dynamic way) as benchmarks of a wide range of arousal states across different reference states of consciousness (e.g., awake, sleep stages, ketamine, sevoflurane). We show a tendency toward high PLE and low LZC, with high intra-subject fluctuations and inter-subject variability in a cohort of CLIS patients with values graded along different arousal states as in our reference data sets. In conclusion, changes in brain dynamics indicate altered arousal in CLIS. Specifically, PLE and LZC are potentially relevant biomarkers to identify or diagnose the arousal level in CLIS and to determine the optimal time point for treatment, including communication attempts.}, } @article {pmid37473705, year = {2023}, author = {Chen, W and Li, S and Bai, D and Li, Z and Liu, H and Bai, L and Pan, L}, title = {Detoxification mechanism of herbicide in Polypogon fugax and its influence on rhizosphere enzyme activities.}, journal = {Ecotoxicology and environmental safety}, volume = {263}, number = {}, pages = {115263}, doi = {10.1016/j.ecoenv.2023.115263}, pmid = {37473705}, issn = {1090-2414}, mesh = {*Herbicides/toxicity ; Molecular Docking Simulation ; Rhizosphere ; Poaceae/metabolism ; Herbicide Resistance/genetics ; Plant Proteins/metabolism ; }, abstract = {The excessive use of chemical herbicides has resulted in evolution of herbicide-resistant weeds. Cytochrome P450 monooxygenases (P450s) are vital detoxification enzymes for herbicide-resistant weeds. Herein, we confirmed a resistant (R) Polypogon fugax population showing resistance to quizalofop-p-ethyl, acetolactate synthase (ALS)-inhibiting herbicide pyroxsulam, and several other ACCase (acetyl-CoA carboxylase)-inhibiting herbicides. Molecular analysis revealed no target-site gene mutations in the R population. Foliar spraying with malathion clearly reversed the quizalofop-p-ethyl phytotoxicity. Higher level of quizalofop-p-ethyl degradation was confirmed in the R population using HPLC analysis. Subsequently, RNA-Seq transcriptome analysis indicated that the overexpression of CYP89A2 gene appeared to be responsible for reducing quizalofop-p-ethyl phytotoxicity. The molecular docking results supported a metabolic effect of CYP89A2 protein on most herbicides tested. Furthermore, we found that low doses of herbicides stimulated the rhizosphere enzyme activities in P. fugax and the increase of rhizosphere dehydrogenase of R population may be related to its resistance mechanism. In summary, our research has shown that metabolic herbicide resistance mediated by CYP89A2, contributes to quizalofop-p-ethyl resistance in P. fugax.}, } @article {pmid37473581, year = {2023}, author = {Woo, E and Bredvik, K and Liu, B and Fuchs, TJ and Manfredi, G and Konrad, C}, title = {Machine learning approaches based on fibroblast morphometry do not predict ALS.}, journal = {Neurobiology of aging}, volume = {130}, number = {}, pages = {80-83}, doi = {10.1016/j.neurobiolaging.2023.06.010}, pmid = {37473581}, issn = {1558-1497}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/metabolism ; Biomarkers ; Endoplasmic Reticulum/metabolism ; Machine Learning ; Fibroblasts/metabolism ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a devastating neuromuscular disease with limited therapeutic options. Biomarkers are needed for early disease detection, clinical trial design, and personalized medicine. Early evidence suggests that specific morphometric features in ALS primary skin fibroblasts may be used as biomarkers; however, this hypothesis has not been rigorously tested in conclusively large fibroblast populations. Here, we imaged ALS-relevant organelles (mitochondria, endoplasmic reticulum, lysosomes) and proteins (TAR DNA-binding protein 43, Ras GTPase-activating protein-binding protein 1, heat-shock protein 60) at baseline and under stress perturbations and tested their predictive power on a total set of 443 human fibroblast lines from ALS and healthy individuals. Machine learning approaches were able to confidently predict stress perturbation states (ROC-AUC ∼0.99) but not disease groups or clinical features (ROC-AUC 0.58-0.64). Our findings indicate that multivariate models using patient-derived fibroblast morphometry can accurately predict different stressors but are insufficient to develop viable ALS biomarkers.}, } @article {pmid37471224, year = {2023}, author = {Park, J and Wu, Y and Shao, W and Gendron, TF and van der Spek, SJF and Sultanakhmetov, G and Basu, A and Castellanos Otero, P and Jones, CJ and Jansen-West, K and Daughrity, LM and Phanse, S and Del Rosso, G and Tong, J and Castanedes-Casey, M and Jiang, L and Libera, J and Oskarsson, B and Dickson, DW and Sanders, DW and Brangwynne, CP and Emili, A and Wolozin, B and Petrucelli, L and Zhang, YJ}, title = {Poly(GR) interacts with key stress granule factors promoting its assembly into cytoplasmic inclusions.}, journal = {Cell reports}, volume = {42}, number = {8}, pages = {112822}, pmid = {37471224}, issn = {2211-1247}, support = {R35 NS097273/NS/NINDS NIH HHS/United States ; RF1 AG062171/AG/NIA NIH HHS/United States ; U01 AG072577/AG/NIA NIH HHS/United States ; RF1 AG062077/AG/NIA NIH HHS/United States ; P01 AG019724/AG/NIA NIH HHS/United States ; R21 NS127331/NS/NINDS NIH HHS/United States ; R01 NS117461/NS/NINDS NIH HHS/United States ; RF1 AG061706/AG/NIA NIH HHS/United States ; P01 NS084974/NS/NINDS NIH HHS/United States ; R01 AG080810/AG/NIA NIH HHS/United States ; P01 NS099114/NS/NINDS NIH HHS/United States ; U54 NS123743/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Mice ; Humans ; *Amyotrophic Lateral Sclerosis/pathology ; DNA Helicases/metabolism ; Stress Granules ; DNA Repeat Expansion ; Poly-ADP-Ribose Binding Proteins/genetics/metabolism ; RNA Helicases/genetics/metabolism ; RNA Recognition Motif Proteins/metabolism ; *Frontotemporal Dementia/metabolism ; Inclusion Bodies/metabolism ; Heat-Shock Proteins/metabolism ; RNA/metabolism ; C9orf72 Protein/genetics/metabolism ; }, abstract = {C9orf72 repeat expansions are the most common genetic cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). Poly(GR) proteins are toxic to neurons by forming cytoplasmic inclusions that sequester RNA-binding proteins including stress granule (SG) proteins. However, little is known of the factors governing poly(GR) inclusion formation. Here, we show that poly(GR) infiltrates a finely tuned network of protein-RNA interactions underpinning SG formation. It interacts with G3BP1, the key driver of SG assembly and a protein we found is critical for poly(GR) inclusion formation. Moreover, we discovered that N[6]-methyladenosine (m6A)-modified mRNAs and m6A-binding YTHDF proteins not only co-localize with poly(GR) inclusions in brains of c9FTD/ALS mouse models and patients with c9FTD, they promote poly(GR) inclusion formation via the incorporation of RNA into the inclusions. Our findings thus suggest that interrupting interactions between poly(GR) and G3BP1 or YTHDF1 proteins or decreasing poly(GR) altogether represent promising therapeutic strategies to combat c9FTD/ALS pathogenesis.}, } @article {pmid37470509, year = {2023}, author = {Strnad, P and San Martin, J}, title = {RNAi therapeutics for diseases involving protein aggregation: fazirsiran for alpha-1 antitrypsin deficiency-associated liver disease.}, journal = {Expert opinion on investigational drugs}, volume = {32}, number = {7}, pages = {571-581}, doi = {10.1080/13543784.2023.2239707}, pmid = {37470509}, issn = {1744-7658}, mesh = {Humans ; *Protein Aggregates ; RNA Interference ; RNAi Therapeutics ; *alpha 1-Antitrypsin Deficiency/complications/genetics/therapy ; RNA, Small Interfering ; }, abstract = {INTRODUCTION: Therapeutic agents that prevent protein misfolding or promote protein clearance are being studied to treat proteotoxic diseases. Among them, alpha-1 antitrypsin deficiency (AATD) is caused by mutations in the alpha-1 antitrypsin (SERPINA1) gene. Fazirsiran is a small interfering RNA (siRNA) that is intended to address the underlying cause of liver disease associated with AATD through the RNA interference (RNAi) mechanism.

AREAS COVERED: This article describes the role of misfolded proteins and protein aggregates in disease and options for therapeutic approaches. The RNAi mechanism is discussed, along with how the siRNA therapeutic fazirsiran for the treatment of AATD was developed. We also describe the implications of siRNA therapeutics in extrahepatic diseases.

EXPERT OPINION: Using RNAi as a therapeutic approach is well suited to treat disease in conditions where an excess of a protein or the effect of an abnormal mutated protein causes disease. The results observed for the first few siRNA therapeutics that were approved or are in development provide an important promise for the development of future drugs that can address such conditions in a specific and targeted way. Current developments should enable the use of RNAi therapeutics outside the liver, where there are many more possible diseases to address.}, } @article {pmid37470197, year = {2023}, author = {Zhan, Z and Fu, J and Chen, H and Pan, H and Weng, S and He, J and Guo, C}, title = {Development and characterization of a spleen cell line from yellowfin seabream Acanthopagrus latus and its susceptibility to Mandarinfish ranavirus.}, journal = {Journal of fish diseases}, volume = {46}, number = {11}, pages = {1173-1181}, doi = {10.1111/jfd.13837}, pmid = {37470197}, issn = {1365-2761}, support = {//Agriculture Research System of China/ ; //Guangdong Basic and Applied Basic Research Foundation/ ; //Guangdong Key Research and Development Program/ ; //Guangdong Laboratory for Lingnan Modern Agriculture/ ; //Guangdong Provincial Special Fund for Modern Agriculture Industry Technology Innovation Teams/ ; //Innovation Group Project of Southern Marine Science and Engineering Guangdong Laboratory (Zhuhai)/ ; //National Key Research and Development Program of China/ ; }, abstract = {Yellowfin seabream (Acanthopagrus latus) is one of the most commercially important marine fish in China. In this study, a new continuous cell line, named ALS cells, was developed from the spleen tissue of A. latus. The cell line was maintained in Dulbecco's modified Eagle medium/Nutrient Mixture F-12 Ham (DMEM/F-12) supplemented with 10% fetal bovine serum (FBS) and successfully cultured up to 50 passages. The cell line was authenticated by amplifying and sequencing mitochondrial cytochrome C oxidase subunit-I (coi-I) gene. The ALS cell line had the maximum growth rate in DMEM/F-12 medium containing 20% FBS at 27°C. Chromosome number analysis showed that the ALS cells have a modal diploid chromosome number of 34. The ALS cell line was transfected with the pEGFP-N1 plasmid, and green fluorescence was observed. The ALS cell line was used for testing Mandarinfish ranavirus (MRV) susceptibility, and the cytopathic effects in the cell line were observed at 4 days post-infection (dpi). Furthermore, the susceptibility of the ALS cell line to MRV and the levels of MRV mRNA and viral loads were found to be significantly increased at 1-7 dpi. This study revealed that the ALS cell line could be useful for molecular, virological, and biotechnological studies on yellowfin seabream.}, } @article {pmid37469832, year = {2023}, author = {Mora, S and Allodi, I}, title = {Neural circuit and synaptic dysfunctions in ALS-FTD pathology.}, journal = {Frontiers in neural circuits}, volume = {17}, number = {}, pages = {1208876}, pmid = {37469832}, issn = {1662-5110}, mesh = {Animals ; *Amyotrophic Lateral Sclerosis/genetics/pathology ; *Frontotemporal Dementia/complications/genetics/pathology ; Brain ; Cognition ; }, abstract = {Action selection is a capital feature of cognition that guides behavior in processes that range from motor patterns to executive functions. Here, the ongoing actions need to be monitored and adjusted in response to sensory stimuli to increase the chances of reaching the goal. As higher hierarchical processes, these functions rely on complex neural circuits, and connective loops found within the brain and the spinal cord. Successful execution of motor behaviors depends, first, on proper selection of actions, and second, on implementation of motor commands. Thus, pathological conditions crucially affecting the integrity and preservation of these circuits and their connectivity will heavily impact goal-oriented motor behaviors. Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD) are two neurodegenerative disorders known to share disease etiology and pathophysiology. New evidence in the field of ALS-FTD has shown degeneration of specific neural circuits and alterations in synaptic connectivity, contributing to neuronal degeneration, which leads to the impairment of motor commands and executive functions. This evidence is based on studies performed on animal models of disease, post-mortem tissue, and patient derived stem cells. In the present work, we review the existing evidence supporting pathological loss of connectivity and selective impairment of neural circuits in ALS and FTD, two diseases which share strong genetic causes and impairment in motor and executive functions.}, } @article {pmid37469125, year = {2023}, author = {Ghaderi, S and Fatehi, F and Kalra, S and Batouli, SAH}, title = {MRI biomarkers for memory-related impairment in amyotrophic lateral sclerosis: a systematic review.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {}, number = {}, pages = {1-17}, doi = {10.1080/21678421.2023.2236651}, pmid = {37469125}, issn = {2167-9223}, abstract = {Introduction: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder associated with cognitive and behavioral impairments and motor symptoms. Magnetic resonance imaging (MRI) biomarkers have been investigated as potential tools for detecting and monitoring memory-related impairment in ALS. Our objective was to examine the importance of identifying MRI biomarkers for memory-related impairment in ALS, motor neuron disease (MND), and ALS frontotemporal dementia (FTD) (ALS-FTD) patients. Methods: PubMed and Scopus databases were searched. Keywords covering magnetic resonance imaging, ALS, MND, and memory impairments were searched. There were a total of 25 studies included in our work here. Results: The structural MRI (sMRI) studies reported gray matter (GM) atrophy in the regions associated with memory processing, such as the hippocampus and parahippocampal gyrus (PhG), in ALS patients. The diffusion tensor imaging (DTI) studies showed white matter (WM) alterations in the corticospinal tract (CST) and other tracts that are related to motor and extra-motor functions, and these alterations were associated with memory and executive function impairments in ALS. The functional MRI (fMRI) studies also demonstrated an altered activation in the prefrontal cortex, limbic system, and other brain regions involved in memory and emotional processing in ALS patients. Conclusion: MRI biomarkers show promise in uncovering the neural mechanisms of memory-related impairment in ALS. Nonetheless, addressing challenges such as sample sizes, imaging protocols, and longitudinal studies is crucial for future research. Ultimately, MRI biomarkers have the potential to be a tool for detecting and monitoring memory-related impairments in ALS.}, } @article {pmid37467887, year = {2023}, author = {Troxell, DA and Bach, JR and Nilsestuen, JO}, title = {Mechanical Insufflation-Exsufflation Implementation and Management, Aided by Graphics Analysis.}, journal = {Chest}, volume = {164}, number = {6}, pages = {1505-1511}, doi = {10.1016/j.chest.2023.07.007}, pmid = {37467887}, issn = {1931-3543}, mesh = {Humans ; *Insufflation ; Respiration, Artificial ; Lung ; *Respiratory Insufficiency/therapy ; Cough ; }, abstract = {Mechanical insufflation-exsufflation (MIE) facilitates airway clearance to mitigate respiratory infection, decompensation, and ultimately the need for intubation and placement of a tracheostomy tube. Despite widespread adoption as a respiratory support intervention for motor neuron disease, muscular dystrophy, spinal cord injury, and other diseases associated with ventilatory pump failure and ineffective cough peak flow, there is debate in the clinical community about how to optimize settings when MIE is implemented. This article will demonstrate the clinical utility of MIE graphics in titrating the initial MIE settings, guiding upper airway and lung protective strategies and providing insight to clinicians for ongoing clinical management.}, } @article {pmid37467213, year = {2023}, author = {Oey, A and McClure, M and Symons, JA and Chanda, S and Fry, J and Smith, PF and Luciani, K and Fayon, M and Chokephaibulkit, K and Uppala, R and Bernatoniene, J and Furuno, K and Stanley, T and Huntjens, D and Witek, J and , }, title = {Lumicitabine, an orally administered nucleoside analog, in infants hospitalized with respiratory syncytial virus (RSV) infection: Safety, efficacy, and pharmacokinetic results.}, journal = {PloS one}, volume = {18}, number = {7}, pages = {e0288271}, pmid = {37467213}, issn = {1932-6203}, mesh = {Adult ; Child ; Humans ; Infant ; Infant, Newborn ; Antiviral Agents/adverse effects ; *Neutropenia/complications ; Nucleosides/therapeutic use ; *Respiratory Syncytial Virus Infections ; *Respiratory Syncytial Virus, Human ; }, abstract = {Respiratory syncytial virus (RSV) infection is the leading cause of infant hospitalizations and mortality. Lumicitabine, an oral nucleoside analog was studied for the treatment of RSV. The phase 1b and phase 2b studies reported here assessed the safety, pharmacokinetics, and pharmacodynamics of lumicitabine in infants/neonates hospitalized with RSV. In the phase 1b study, infants (≥1 to ≤12 months) and neonates (<28 days) received a single-ascending or multiple-ascending doses (single loading dose [LD] then 9 maintenance doses [MD] of lumicitabine, or placebo [3:1]). In the phase 2b study, infants/children (28 days to ≤36 months old) received lumicitabine 40/20 mg/kg, 60/40 mg/kg LD/MD twice-daily or placebo (1:1:1) for 5 days. Safety, pharmacokinetics, and efficacy parameters were assessed over 28 days. Lumicitabine was associated with a dose-related increase in the incidence and severity of reversible neutropenia. Plasma levels of ALS-008112, the active nucleoside analog, were dose-proportional with comparable mean exposure levels at the highest doses in both studies. There were no significant differences between the lumicitabine groups and placebo in reducing viral load, time to viral non-detectability, and symptom resolution. No emergent resistance-associated substitutions were observed at the RSV L-gene positions of interest. In summary, lumicitabine was associated with a dose-related increase in the incidence and severity of reversible neutropenia and failed to demonstrate antiviral activity in RSV-infected hospitalized infants. This contrasts with the findings of the previous RSV-A adult challenge study where significant antiviral activity was noted, without incidence of neutropenia. Trial registration ClinicalTrials.gov Identifier: NCT02202356 (phase 1b); NCT03333317 (phase 2b).}, } @article {pmid37466825, year = {2024}, author = {Poppe, C and Elger, BS}, title = {Brain-Computer Interfaces, Completely Locked-In State in Neurodegenerative Diseases, and End-of-Life Decisions.}, journal = {Journal of bioethical inquiry}, volume = {21}, number = {1}, pages = {19-27}, pmid = {37466825}, issn = {1872-4353}, mesh = {Humans ; *Brain-Computer Interfaces/ethics ; *Terminal Care/ethics ; *Neurodegenerative Diseases ; *Quality of Life ; *Decision Making/ethics ; Suicide, Assisted/ethics ; Locked-In Syndrome ; Mental Competency ; }, abstract = {In the future, policies surrounding end-of-life decisions will be faced with the question of whether competent people in a completely locked-in state should be enabled to make end-of-life decisions via brain-computer interfaces (BCI). This article raises ethical issues with acting through BCIs in the context of these decisions, specifically self-administration requirements within assisted suicide policies. We argue that enabling patients to end their life even once they have entered completely locked-in state might, paradoxically, prolong and uphold their quality of life.}, } @article {pmid37466726, year = {2023}, author = {Gittings, LM and Alsop, EB and Antone, J and Singer, M and Whitsett, TG and Sattler, R and Van Keuren-Jensen, K}, title = {Cryptic exon detection and transcriptomic changes revealed in single-nuclei RNA sequencing of C9ORF72 patients spanning the ALS-FTD spectrum.}, journal = {Acta neuropathologica}, volume = {146}, number = {3}, pages = {433-450}, pmid = {37466726}, issn = {1432-0533}, support = {P30 AG019610/AG/NIA NIH HHS/United States ; P30 AG072980/AG/NIA NIH HHS/United States ; U24 NS072026/NS/NINDS NIH HHS/United States ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/pathology ; *Frontotemporal Dementia/genetics/pathology ; C9orf72 Protein/genetics/metabolism ; Transcriptome ; *Pick Disease of the Brain/genetics ; DNA-Binding Proteins/genetics/metabolism ; Exons ; Sequence Analysis, RNA ; }, abstract = {The C9ORF72-linked diseases amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are characterized by the nuclear depletion and cytoplasmic accumulation of TAR DNA-binding protein 43 (TDP-43). Recent studies have shown that the loss of TDP-43 function leads to the inclusion of cryptic exons (CE) in several RNA transcript targets of TDP-43. Here, we show for the first time the detection of CEs in a single-nuclei RNA sequencing (snRNA-seq) dataset obtained from frontal and occipital cortices of C9ORF72 patients that phenotypically span the ALS-FTD disease spectrum. We assessed each cellular cluster for detection of recently described TDP-43-induced CEs. Transcripts containing CEs in the genes STMN2 and KALRN were detected in the frontal cortex of all C9ORF72 disease groups with the highest frequency in excitatory neurons in the C9ORF72-FTD group. Within the excitatory neurons, the cluster with the highest proportion of cells containing a CE had transcriptomic similarities to von Economo neurons, which are known to be vulnerable to TDP-43 pathology and selectively lost in C9ORF72-FTD. Differential gene expression and pathway analysis of CE-containing neurons revealed multiple dysregulated metabolic processes. Our findings reveal novel insights into the transcriptomic changes of neurons vulnerable to TDP-43 pathology.}, } @article {pmid37466098, year = {2023}, author = {Borghero, G and Sechi, MM and Vasta, R and Pierri, V and Pili, F and Pateri, I and Pilotto, S and Ercoli, T and Muroni, A and Chiò, A and Defazio, G}, title = {Spatial clustering of amyotrophic lateral sclerosis in Sardinia, Italy: The contribution of age, sex, and genetic factors.}, journal = {Muscle & nerve}, volume = {68}, number = {3}, pages = {323-328}, doi = {10.1002/mus.27939}, pmid = {37466098}, issn = {1097-4598}, mesh = {Humans ; Male ; *Amyotrophic Lateral Sclerosis/epidemiology/genetics ; Mutation/genetics ; Incidence ; Risk Factors ; Cluster Analysis ; Italy/epidemiology ; }, abstract = {INTRODUCTION/AIMS: Several microgeographic clusters of higher/lower incidence of amyotrophic lateral sclerosis (ALS) have been identified worldwide. Differences in the distribution of local factors were proposed to explain the excess ALS risk, whereas the contribution of known genetic/epigenetic factors remains unclear. The aim is to identify restricted areas of higher risk in Sardinia and to assess whether age, sex, and the most common causative genetic mutations in Sardinia (C9orf72 and TARDBP mutations) contributed to the variation in the ALS risk.

METHODS: We performed an ad hoc analysis of the 10-y population-based incident cohort of ALS cases from a recent study of a large Sardinian area. Cluster analysis was performed by age- and sex-adjusted Kulldorff's spatial scan statistic.

RESULTS: We identified a statistically significant cluster of higher ALS incidence in a relatively large area including 34 municipalities and >100,000 individuals. The investigated genetic mutations were more frequent in the cluster area than outside. Regardless of the genetic mutations, the excess of ALS risk was significantly associated with either sex or with age ≥ 65 y. Finally, an additive interaction between older age and male sex contributed to the excess of ALS risk in the cluster area but not outside.

DISCUSSION: Our analysis demonstrated that known genetic factors, age, and sex may contribute to microgeographic variation in ALS incidence. The significant additive interaction between older age and male sex we found in the high-incidence cluster could suggest the presence of a third factor connecting the analyzed risk factors.}, } @article {pmid37465879, year = {2023}, author = {Alhindi, A and Shand, M and Smith, HL and Leite, AS and Huang, YT and van der Hoorn, D and Ridgway, Z and Faller, KME and Jones, RA and Gillingwater, TH and Chaytow, H}, title = {Neuromuscular junction denervation and terminal Schwann cell loss in the hTDP-43 overexpression mouse model of amyotrophic lateral sclerosis.}, journal = {Neuropathology and applied neurobiology}, volume = {49}, number = {4}, pages = {e12925}, doi = {10.1111/nan.12925}, pmid = {37465879}, issn = {1365-2990}, mesh = {Mice ; Animals ; *Amyotrophic Lateral Sclerosis/pathology ; *Neurodegenerative Diseases/pathology ; Neuromuscular Junction/pathology ; Motor Neurons/pathology ; Schwann Cells/metabolism/pathology ; Denervation ; DNA-Binding Proteins/metabolism ; Mice, Transgenic ; Disease Models, Animal ; }, abstract = {AIMS: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with complex aetiology. Despite evidence of neuromuscular junction (NMJ) denervation and 'dying-back' pathology in models of SOD1-dependent ALS, evidence in other genetic forms of ALS is limited by a lack of suitable animal models. TDP-43, a key mediator protein in ALS, is overexpressed in neurons in Thy1-hTDP-43[WT] mice. We therefore aimed to comprehensively analyse NMJ pathology in this model of ALS.

METHODS: Expression of TDP-43 was assessed via western blotting. Immunohistochemistry techniques, alongside NMJ-morph quantification, were used to analyse motor neuron number, NMJ denervation status and terminal Schwann cell morphology.

RESULTS: We present a time course of progressive, region-specific motor neuron pathology in Thy1-hTDP-43[WT] mice. Thy1-driven hTDP-43 expression increased steadily, correlating with developing hindlimb motor weakness and associated motor neuron loss in the spinal cord with a median survival of 21 days. Pronounced NMJ denervation was observed in hindlimb muscles, mild denervation in cranial muscles but no evidence of denervation in either forelimb or trunk muscles. NMJ pathology was restricted to motor nerve terminals, with denervation following the same time course as motor neuron loss. Terminal Schwann cells were lost from NMJs in hindlimb muscles, directly correlating with denervation status.

CONCLUSIONS: Thy1-hTDP-43[WT] mice represent a severe model of ALS, with NMJ pathology/denervation of distal muscles and motor neuron loss, as observed in ALS patients. This model therefore provides an ideal platform to investigate mechanisms of dying-back pathology, as well as NMJ-targeting disease-modifying therapies in ALS.}, } @article {pmid37465321, year = {2023}, author = {Gnoni, V and Zoccolella, S and Giugno, A and Urso, D and Tamburrino, L and Filardi, M and Logroscino, G}, title = {Hypothalamus and amyotrophic lateral sclerosis: potential implications in sleep disorders.}, journal = {Frontiers in aging neuroscience}, volume = {15}, number = {}, pages = {1193483}, pmid = {37465321}, issn = {1663-4365}, abstract = {Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease that affects both motor and non-motor functions, including sleep regulation. Emerging evidence suggests that the hypothalamus, a brain region that plays a critical role in sleep-wake regulation, may be involved in the pathogenesis of ALS-related sleep disturbances. In this review, we have summarized results of studies on sleep disorders in ALS published between 2000 and 2023. Thereafter, we examined possible mechanisms by which hypothalamic dysfunctions may contribute to ALS-related sleep disturbances. Achieving a deeper understanding of the relationship between hypothalamic dysfunction and sleep disturbances in ALS can help improve the overall management of ALS and reduce the burden on patients and their families.}, } @article {pmid37465304, year = {2023}, author = {Kargbo, RB}, title = {Microbiome-Gut-Brain Axis Modulation: New Approaches in Treatment of Parkinson's Disease and Amyotrophic Lateral Sclerosis.}, journal = {ACS medicinal chemistry letters}, volume = {14}, number = {7}, pages = {886-888}, pmid = {37465304}, issn = {1948-5875}, abstract = {Parkinson's Disease (PD) is a neurodegenerative movement disorder characterized by symptoms like resting tremor, rigidity, bradykinesia, and postural instability, mainly due to dopamine depletion and degeneration of dopaminergic neurons. Mitochondrial dysfunction plays a critical role in the disease's progression, while amyotrophic Lateral Sclerosis (ALS), or Lou Gehrig's disease, is a fatal progressive neurodegenerative disease characterized by significant motor neuron loss in the primary motor cortex, brainstem, and spinal cord. This loss results in impaired movements such as breathing, leading to death within 2-5 years of diagnosis. Patients experience muscle weakness in the hands, arms, legs, and swallowing muscles and may require breathing aids. This Patent Highlight describes blends, such as microbiome compositions, that can be used to treat various diseases or conditions, particularly those affecting the nervous system, like neurodegenerative diseases (PD and ALS).}, } @article {pmid37463628, year = {2023}, author = {Soumya, BS and Shreenidhi, VP and Agarwal, A and Gandhirajan, RK and Dharmarajan, A and Warrier, S}, title = {Unwinding the role of Wnt signaling cascade and molecular triggers of motor neuron degeneration in amyotrophic lateral sclerosis (ALS).}, journal = {Cellular signalling}, volume = {110}, number = {}, pages = {110807}, doi = {10.1016/j.cellsig.2023.110807}, pmid = {37463628}, issn = {1873-3913}, mesh = {Humans ; Animals ; *Amyotrophic Lateral Sclerosis/metabolism ; Wnt Signaling Pathway ; Motor Neurons/metabolism ; Oxidative Stress ; Nerve Degeneration/metabolism/pathology ; Disease Models, Animal ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative condition, triggered by various factors causing the degeneration of upper and lower motor neurons, resulting in progressive muscle wasting, paralysis, and death. Multiple in vivo and in vitro models have been established to unravel the molecular events leading to the deterioration of motor neurons in ALS. The canonical and non-canonical Wnt signaling pathway has been implicated to play a crucial role in the progression of neurodegenerative disorders. This review discusses the role of Wnt signaling in the reported causes of ALS such as oxidative stress, mitochondrial dysfunction, autophagy, and apoptosis. Mutations in ALS-associated genes such as SOD1, C9orf72, TDP43, FUS, and OPTN cause an imbalance in neuronal integrity and homeostasis leading to motor neuron demise. Wnt signaling is also observed to play a crucial role in the muscle sparing of oculomotor neurons. The non-canonical Wnt/Ca[2+] pathway which regulates intrinsic electrophysiological properties and mobilizes calcium ions to maintain neuronal integrity has been found to be altered in the stem cell-derived ALS model. Thus, the interplay of dysregulated canonical and non-canonical Wnt pathways in multiple motor neuron disease models has shown that Wnt contributes to disease progression indicating it to be utilized as a potential target for ALS.}, } @article {pmid37462337, year = {2023}, author = {Genuis, SK and Luth, W and Bubela, T and Johnston, WS}, title = {What do people affected by amyotrophic lateral sclerosis want from health communications? Evidence from the ALS Talk Project.}, journal = {Muscle & nerve}, volume = {68}, number = {3}, pages = {286-295}, doi = {10.1002/mus.27935}, pmid = {37462337}, issn = {1097-4598}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy ; *Health Communication ; Quality of Life ; Caregivers ; Health Personnel ; }, abstract = {INTRODUCTION/AIMS: Health communication is central to effective, supportive amyotrophic lateral sclerosis (ALS) clinical care. Guidance for ALS communication is limited, focuses on diagnosis disclosure, and frequently relies on expert consensus and/or reviews. Patient-based evidence is needed to guide ALS health communication. We investigated how the experiences of ALS patients and family caregivers can inform effective communication practices from diagnosis to end-of-life.

METHODS: Data were drawn from the ALS Talk Project, an asynchronous, online focus group study. Seven focus groups and five interviews (105 participants) were conducted. Data were qualitatively analyzed using directed content analysis and the constant-comparative approach.

RESULTS: We found four primary themes: communication content, communication circumstances, information sufficiency, and communication manner. Data indicate participants relied on clinicians for medical information but also wanted practical information; health communication should attend to the circumstances within which conversations occur; information must be sufficient for individual needs, without overwhelming; and an empathetic, direct, and honest manner facilitated trust. Participants identified communication challenges and strategies to improve communication across major themes, including stepwise approaches and conversations tailored to individuals and their heterogeneous disease experiences.

DISCUSSION: Healthcare professionals should discuss patient/caregiver communication preferences early in the therapeutic relationship, co-develop a communication agreement, and update the agreement in response to changing needs and disease progression. This will foster regular discussion of information needs and promote timely discussions of challenging topics, including advance care, while giving patients and families a sense of control. Findings may have implications for other neuromuscular disease and/or seriously ill populations.}, } @article {pmid37461717, year = {2023}, author = {Provasek, VE and Kodavati, M and Guo, W and Wang, H and Boldogh, I and Van Den Bosch, L and Britz, G and Hegde, M}, title = {lncRNA Sequencing Reveals Neurodegeneration-associated FUS Mutations Alter Transcriptional Landscape of iPS Cells That Persists In Motor Neurons.}, journal = {Research square}, volume = {}, number = {}, pages = {}, pmid = {37461717}, issn = {2693-5015}, support = {R01 NS088645/NS/NINDS NIH HHS/United States ; R01 NS094535/NS/NINDS NIH HHS/United States ; R03 AG064266/AG/NIA NIH HHS/United States ; RF1 NS112719/NS/NINDS NIH HHS/United States ; }, abstract = {Fused-in Sarcoma (FUS) gene mutations have been implicated in amyotrophic lateral sclerosis (ALS). This study aimed to investigate the impact of FUS mutations (R521H and P525L) on the transcriptome of induced pluripotent stem cells (iPSCs) and iPSC-derived motor neurons (iMNs). Using RNA sequencing (RNA Seq), we characterized differentially expressed genes (DEGs), differentially expressed lncRNAs (DELs), and subsequently predicted lncRNA-mRNA target pairs (TAR pairs). Our results show that FUS mutations significantly altered expression profiles of mRNAs and lncRNAs in iPSCs. We identified key differentially regulated TAR pairs, including LMO3, TMEM132D, ERMN, GPR149, CRACD, and ZNF404 in mutant FUS iPSCs. We performed reverse transcription PCR (RT-PCR) validation in iPSCs and iMNs. Validation confirmed RNA-Seq findings and suggested that mutant FUS-induced transcriptional alterations persisted from iPSCs into differentiated iMNs. Functional enrichment analyses of DEGs indicated pathways associated with neuronal development and carcinogenesis that were likely altered by FUS mutations. Ingenuity Pathway Analysis (IPA) and GO network analysis of lncRNA-targeted mRNAs indicated associations related to RNA metabolism, lncRNA regulation, and DNA damage repair. Our findings provide insights into the molecular mechanisms underlying the pathophysiology of ALS-associated FUS mutations and suggest potential therapeutic targets for the treatment of ALS.}, } @article {pmid37461319, year = {2023}, author = {Fujino, Y and Ueyama, M and Ishiguro, T and Ozawa, D and Ito, H and Sugiki, T and Murata, A and Ishiguro, A and Gendron, T and Mori, K and Tokuda, E and Taminato, T and Konno, T and Koyama, A and Kawabe, Y and Takeuchi, T and Furukawa, Y and Fujiwara, T and Ikeda, M and Mizuno, T and Mochizuki, H and Mizusawa, H and Wada, K and Ishikawa, K and Onodera, O and Nakatani, K and Petrucelli, L and Taguchi, H and Nagai, Y}, title = {FUS regulates RAN translation through modulating the G-quadruplex structure of GGGGCC repeat RNA in C9orf72-linked ALS/FTD.}, journal = {eLife}, volume = {12}, number = {}, pages = {}, pmid = {37461319}, issn = {2050-084X}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/pathology ; C9orf72 Protein/genetics/metabolism ; *Frontotemporal Dementia/pathology ; RNA/metabolism ; RNA-Binding Protein FUS/genetics ; RNA-Binding Proteins/genetics ; Drosophila/genetics ; }, abstract = {Abnormal expansions of GGGGCC repeat sequence in the noncoding region of the C9orf72 gene is the most common cause of familial amyotrophic lateral sclerosis and frontotemporal dementia (C9-ALS/FTD). The expanded repeat sequence is translated into dipeptide repeat proteins (DPRs) by noncanonical repeat-associated non-AUG (RAN) translation. Since DPRs play central roles in the pathogenesis of C9-ALS/FTD, we here investigate the regulatory mechanisms of RAN translation, focusing on the effects of RNA-binding proteins (RBPs) targeting GGGGCC repeat RNAs. Using C9-ALS/FTD model flies, we demonstrated that the ALS/FTD-linked RBP FUS suppresses RAN translation and neurodegeneration in an RNA-binding activity-dependent manner. Moreover, we found that FUS directly binds to and modulates the G-quadruplex structure of GGGGCC repeat RNA as an RNA chaperone, resulting in the suppression of RAN translation in vitro. These results reveal a previously unrecognized regulatory mechanism of RAN translation by G-quadruplex-targeting RBPs, providing therapeutic insights for C9-ALS/FTD and other repeat expansion diseases.}, } @article {pmid37461167, year = {2023}, author = {Berger, A and Locatelli, M and Arcila-Londono, X and Hayat, G and Olney, N and Wymer, J and Gwathmey, K and Lunetta, C and Heiman-Patterson, T and Ajroud-Driss, S and Macklin, EA and Bind, MA and Goslin, K and Stuchiner, T and Brown, L and Bazan, T and Regan, T and Adamo, A and Ferment, V and Schroeder, C and Somers, M and Manousakis, G and Faulconer, K and Sinani, E and Mirochnick, J and Yu, H and Sherman, AV and Walk, D and , }, title = {The natural history of ALS: Baseline characteristics from a multicenter clinical cohort.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {}, number = {}, pages = {1-9}, doi = {10.1080/21678421.2023.2232812}, pmid = {37461167}, issn = {2167-9223}, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a rare disease with urgent need for improved treatment. Despite the acceleration of research in recent years, there is a need to understand the full natural history of the disease. As only 40% of people living with ALS are eligible for typical clinical trials, clinical trial datasets may not generalize to the full ALS population. While biomarker and cohort studies have more generous inclusion criteria, these too may not represent the full range of phenotypes, particularly if the burden for participation is high. To permit a complete understanding of the heterogeneity of ALS, comprehensive data on the full range of people with ALS is needed.

METHODS: The ALS Natural History Consortium (ALS NHC) consists of nine ALS clinics and was created to build a comprehensive dataset reflective of the ALS population. At each clinic, most patients are asked to participate and about 95% do. After obtaining consent, a minimum dataset is abstracted from each participant's electronic health record. Participant burden is therefore minimal.

RESULTS: Data on 1925 ALS patients were submitted as of 9 December 2022. ALS NHC participants were more heterogeneous relative to anonymized clinical trial data from the Pooled Resource Open-Access ALS Clinical Trials (PRO-ACT) database. The ALS NHC includes ALS patients of older age of onset and a broader distribution of El Escorial categories, than the PRO-ACT database.

CONCLUSIONS: ALS NHC participants had a higher diversity of diagnostic and demographic data compared to ALS clinical trial participants.Key MessagesWhat is already known on this topic: Current knowledge of the natural history of ALS derives largely from regional and national registries that have broad representation of the population of people living with ALS but do not always collect covariates and clinical outcomes. Clinical studies with rich datasets of participant characteristics and validated clinical outcomes have stricter inclusion and exclusion criteria that may not be generalizable to the full ALS population.What this study adds: To bridge this gap, we collected baseline characteristics for a sample of the population of people living with ALS seen at a consortium of ALS clinics that collect extensive, pre-specified participant-level data, including validated outcome measures.How this study might affect research, practice, or policy: A clinic-based longitudinal dataset can improve our understanding of the natural history of ALS and can be used to inform the design and analysis of clinical trials and health economics studies, to help the prediction of clinical course, to find matched controls for open label extension trials and expanded access protocols, and to document real-world evidence of the impact of novel treatments and changes in care practice.}, } @article {pmid37460793, year = {2023}, author = {Gawlik-Dziki, U and Wrzesińska-Krupa, B and Nowak, R and Pietrzak, W and Zyprych-Walczak, J and Obrępalska-Stęplowska, A}, title = {Herbicide resistance status impacts the profile of non-anthocyanin polyphenolics and some phytomedical properties of edible cornflower (Centaurea cyanus L.) flowers.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {11538}, pmid = {37460793}, issn = {2045-2322}, mesh = {*Herbicide Resistance ; *Herbicides/pharmacology ; Flowers ; Centaurea ; Plant Weeds ; }, abstract = {To ensure sufficient food supply worldwide, plants are treated with pesticides to provide protection against pathogens and pests. Herbicides are the most commonly utilised pesticides, used to reduce the growth of weeds. However, their long-term use has resulted in the emergence of herbicide-resistant biotypes in many weed species. Cornflower (Centaurea cyanus L., Asteraceae) is one of these plants, whose biotypes resistant to herbicides from the group of acetolactate synthase (ALS) inhibitors have begun to emerge in recent years. Some plants, although undesirable in crops and considered as weeds, are of great importance in phytomedicine and food production, and characterised by a high content of health-promoting substances, including antioxidants. Our study aimed to investigate how the acquisition of herbicide resistance affects the health-promoting properties of plants on the example of cornflower, as well as how they are affected by herbicide treatment. To this end, we analysed non-anthocyanin polyphenols and antioxidant capacity in flowers of C. cyanus from herbicide-resistant and susceptible biotypes. Our results indicated significant compositional changes associated with an increase in the content of substances and activities that have health-promoting properties. High antioxidant activity and higher total phenolic and flavonoid compounds as well as reducing power were observed in resistant biotypes. The latter one increased additionally after herbicide treatment which might also suggest their role in the resistance acquisition mechanism. Overall, these results show that the herbicide resistance development, although unfavourable to crop production, may paradoxically have very positive effects for medicinal plants such as cornflower.}, } @article {pmid37460332, year = {2023}, author = {Lacroix, C and Guilhaumou, R and Micallef, J and Bruneteau, G and Desnuelle, C and Blin, O}, title = {Cannabis for the treatment of amyotrophic lateral sclerosis: What is the patients' view?.}, journal = {Revue neurologique}, volume = {179}, number = {9}, pages = {967-974}, doi = {10.1016/j.neurol.2023.03.018}, pmid = {37460332}, issn = {0035-3787}, mesh = {Humans ; *Cannabis/adverse effects ; *Amyotrophic Lateral Sclerosis/drug therapy/complications ; Quality of Life ; *Cannabinoids/adverse effects ; Pain ; }, abstract = {Cannabis may have therapeutic benefits to relieve symptoms of amyotrophic lateral sclerosis (ALS) thanks to its pleiotropic pharmacological activity. This study is the first to present a large questionnaire-based survey about the "real-life" situation regarding cannabis use in the medical context in ALS patients in France. There were 129 respondents and 28 reported the use of cannabis (21.7%) to relieve symptoms of ALS. Participants mostly reported the use of cannabidiol (CBD) oil and cannabis weed and declared benefits both on motor (rigidity, cramps, fasciculations) and non-motor (sleep quality, pain, emotional state, quality of life, depression) symptoms and only eight reported minor adverse reactions (drowsiness, euphoria and dry mouth). Even if cannabis is mostly used outside medical pathways and could expose patients to complications (street and uncontrolled drugs, drug-drug interactions, adverse effects…), most of the participants reported "rational" consumption (legal cannabinoids, with only few combustion and adverse reactions). Despite some limitations, this study highlights the need for further research on the potential benefits of cannabis use for the management of ALS motor and non-motor symptoms. Indeed, there is an urgent need and call for and from patients to know more about cannabis and secure its use in a medical context.}, } @article {pmid37460258, year = {2023}, author = {Pedron, S and Herbert-Maul, A and Sauter, A and Linder, S and Sommer, R and Vomhof, M and Gontscharuk, V and Abu-Omar, K and Thiel, A and Ziemainz, H and Holle, R and Laxy, M}, title = {Preferences of women in difficult life situations for a physical activity programme: protocol of a discrete choice experiment in the German NU-BIG project.}, journal = {BMJ open}, volume = {13}, number = {7}, pages = {e067235}, pmid = {37460258}, issn = {2044-6055}, mesh = {Humans ; Female ; *Choice Behavior ; *Exercise ; Socioeconomic Factors ; Surveys and Questionnaires ; Patient Preference ; }, abstract = {INTRODUCTION: The BIG project ('Bewegung als Investition in die Gesundheit', ie, 'Movement as Investment in Health') was developed in 2005 as a community-based participatory research programme to offer accessible opportunities for physical activity to women in difficult life situations. Since then, the programme has been expanded to eight sites in Germany. A systematic evaluation of BIG is currently being conducted. As part of this effort, we strive to understand the preferences of participating women for different aspects of the programme, and to analyse their willingness to pay.

METHODS AND ANALYSIS: In this protocol, we describe the development and analysis plan of a discrete choice experiment (DCE) to investigate participants' preferences for a physical activity programme for women in difficult life situations. The experiment will be embedded in a questionnaire covering several aspects of participation in the programme (eg, reach, efficacy and further effects) and the socioeconomic characteristics of all active participants. After a thorough search of the literature, BIG documents review and expert interviews, we identified five important attributes of the programme: course times, travel time to the course venue, additional social activities organised by BIG, consideration of wishes and interests for the further planning of courses and costs per course unit. Thereafter, we piloted the experiment with a sample of participants from the target group. After data collection, the experiment will be analysed using a conditional logit model and a latent class analysis to assess eventual heterogeneity in preferences.

ETHICS AND DISSEMINATION: Understanding women's preferences will provide useful insights for the further development of the programme and ultimately increase participation and retention. The questionnaire, the included DCE and the pretest on participants received ethical approval (application no. 20-247_1-B). We plan to disseminate the results of the DCE in peer-reviewed journals, national conferences and among participants and programme coordinators and organisers.}, } @article {pmid37460141, year = {2023}, author = {}, title = {Tofersen (Qalsody) for ALS.}, journal = {The Medical letter on drugs and therapeutics}, volume = {65}, number = {1681}, pages = {113-114}, doi = {10.58347/tml.2023.1681a}, pmid = {37460141}, issn = {1523-2859}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/drug therapy ; Edaravone ; Oligonucleotides ; }, } @article {pmid37459708, year = {2023}, author = {Li, X and Liu, Q and Niu, T and Liu, T and Xin, Z and Zhou, X and Li, R and Li, Z and Jia, L and Liu, Y and Dong, H}, title = {Sleep disorders and white matter integrity in patients with sporadic amyotrophic lateral sclerosis.}, journal = {Sleep medicine}, volume = {109}, number = {}, pages = {170-180}, doi = {10.1016/j.sleep.2023.07.003}, pmid = {37459708}, issn = {1878-5506}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnostic imaging ; *White Matter/diagnostic imaging ; Diffusion Tensor Imaging/methods ; Extremities ; *Sleep Initiation and Maintenance Disorders/complications ; }, abstract = {This study aimed to explore the characteristics of sleep disorders and their relationship with abnormal white-matter integrity in patients with sporadic amyotrophic lateral sclerosis. One hundred and thirty-six patients and 80 healthy controls were screened consecutively, and 56 patients and 43 healthy controls were ultimately analyzed. Sleep disorders were confirmed using the Pittsburgh sleep quality index, the Epworth sleepiness scale, and polysomnography; patients were classified into those with poor and good sleep quality. White-matter integrity was assessed using diffusion tensor imaging and compared between groups to identify the white-matter tracts associated with sleep disorders. The relationship between scores on the Pittsburgh sleep quality index and impaired white-matter tracts was analyzed using multiple regression. Poor sleep quality was more common in patients (adjusted odds ratio, 4.26; p = 0.005). Compared to patients with good sleep quality (n = 30), patients with poor sleep quality (n = 26; 46.4%) showed decreased fractional anisotropy, increased mean diffusivity, and increased radial diffusivity of projection and commissural fibers, and increased radial diffusivity of the right thalamus. The Pittsburgh score showed the best fit with the mean fractional anisotropy of the right anterior limb of the internal capsule (r = - 0.355, p = 0.011) and the mean radial diffusivity of the right thalamus (r = 0.309, p = 0.028). We conclude that sleep disorders are common in patients with sporadic amyotrophic lateral sclerosis and are associated with reduced white-matter integrity. The pathophysiology of amyotrophic lateral sclerosis may contribute directly to sleep disorders.}, } @article {pmid37459678, year = {2023}, author = {Fuentes, CA and Öztop, MH and Rojas-Rioseco, M and Bravo, M and Göksu, AÖ and Manley, M and Castillo, RDP}, title = {Application of segmented analysis via multivariate curve resolution with alternating least squares to [1]H-nuclear magnetic resonance spectroscopy to identify different sugar sources.}, journal = {Food chemistry}, volume = {428}, number = {}, pages = {136817}, doi = {10.1016/j.foodchem.2023.136817}, pmid = {37459678}, issn = {1873-7072}, mesh = {*Sugars ; Multivariate Analysis ; Least-Squares Analysis ; *Carbohydrates ; Magnetic Resonance Spectroscopy ; }, abstract = {The different types of sugar employed in the food industry exhibit chemical similarity and are mostly dominated by sucrose. Owing to the sugar origin of and differences in production, the presence of certain minor organic compounds differs. To differentiate between sugars based on their botanical source, geographical origin, or storage conditions, commercial brown sugars and sugar beet extracts were analyzed by [1]H NMR spectroscopy applying a segmented analysis by means of multivariate curve resolution-alternating least squares (MCR-ALS). Principal component analysis and partial least squares-discriminant analysis yielded excellent differentiation between sugars from different sources after the application of this preprocessing strategy; without loss of chemical information and with direct interpretation of the results. By applying a segmented analysis via MCR-ALS to [1]H NMR sugar data, similar spectroscopic profiles could be differentiated. This improved the selectivity of [1]H NMR spectroscopy for sugar source differentiation which can be useful for industrial sugar authentication purposes.}, } @article {pmid37458987, year = {2023}, author = {Gupta, R and Advani, D and Yadav, D and Ambasta, RK and Kumar, P}, title = {Dissecting the Relationship Between Neuropsychiatric and Neurodegenerative Disorders.}, journal = {Molecular neurobiology}, volume = {60}, number = {11}, pages = {6476-6529}, pmid = {37458987}, issn = {1559-1182}, mesh = {Humans ; Aged ; *Alzheimer Disease/genetics ; *Parkinson Disease ; *Huntington Disease ; *Amyotrophic Lateral Sclerosis ; *Depressive Disorder, Major ; *Autism Spectrum Disorder ; *Neurodegenerative Diseases/metabolism ; }, abstract = {Neurodegenerative diseases (NDDs) and neuropsychiatric disorders (NPDs) are two common causes of death in elderly people, which includes progressive neuronal cell death and behavioral changes. NDDs include Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, multiple sclerosis, and motor neuron disease, characterized by cognitive defects and memory impairment, whereas NPDs include depression, seizures, migraine headaches, eating disorders, addictions, palsies, major depressive disorders, anxiety, and schizophrenia, characterized by behavioral changes. Mounting evidence demonstrated that NDDs and NPDs share an overlapping mechanism, which includes post-translational modifications, the microbiota-gut-brain axis, and signaling events. Mounting evidence demonstrated that various drug molecules, namely, natural compounds, repurposed drugs, multitarget directed ligands, and RNAs, have been potentially implemented as therapeutic agents against NDDs and NPDs. Herein, we highlighted the overlapping mechanism, the role of anxiety/stress-releasing factors, cytosol-to-nucleus signaling, and the microbiota-gut-brain axis in the pathophysiology of NDDs and NPDs. We summarize the therapeutic application of natural compounds, repurposed drugs, and multitarget-directed ligands as therapeutic agents. Lastly, we briefly described the application of RNA interferences as therapeutic agents in the pathogenesis of NDDs and NPDs. Neurodegenerative diseases and neuropsychiatric diseases both share a common signaling molecule and molecular phenomenon, namely, pro-inflammatory cytokines, γCaMKII and MAPK/ERK, chemokine receptors, BBB permeability, and the gut-microbiota-brain axis. Studies have demonstrated that any alterations in the signaling mentioned above molecules and molecular phenomena lead to the pathophysiology of neurodegenerative diseases, namely, Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis, and neuropsychiatric disorders, such as bipolar disorder, schizophrenia, depression, anxiety, autism spectrum disorder, and post-traumatic stress disorder.}, } @article {pmid37458842, year = {2023}, author = {Vigano', M and Mantero, V and Basilico, P and Pirro, F and Ronchi, D and Di Fonzo, A and Salmaggi, A}, title = {Don't forget Allgrove syndrome in adult patients as a bulbar-ALS mimicker.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {44}, number = {10}, pages = {3703-3705}, pmid = {37458842}, issn = {1590-3478}, mesh = {Humans ; Adult ; *Esophageal Achalasia/diagnosis/genetics ; *Amyotrophic Lateral Sclerosis/diagnosis/genetics ; *Adrenal Insufficiency/diagnosis/genetics ; *Lacrimal Apparatus Diseases/diagnosis ; }, abstract = {INTRODUCTION: Allgrove syndrome is a genetic disorder characterized by a multisystem involvement manifesting mainly in childhood with esophageal achalasia, adrenal insufficiency, and alacrima. Associated neurological manifestations are frequent in patients with late-onset forms and include peripheral, central, and autonomic dysfunction. The definitive diagnosis remains genetic, but neurological symptoms/signs could be a relevant clue for the diagnosis.

DISCUSSION: This syndrome is rare, but it is not impossible for it to occur in adults, so all neurologists must be alert. Moreover, in this regard, neurological symptoms can sometimes be very similar to those of motor neuron disease patients, so that, although rare, Allgrove syndrome may also enter into the differential diagnosis with the bulbar variant of amyotrophic lateral sclerosis. Nevertheless, attention to extra-neurological symptoms must remain high as these play an equally important role in reaching the diagnosis.

CASE REPORT: Here we present the case of a patient with some peculiarities that are onset at an advanced age, genetic confirmation of the diagnosis, and prominent neurological involvement, which also opens the differential diagnosis to amyotrophic lateral sclerosis.}, } @article {pmid37458788, year = {2023}, author = {El Mendili, MM and Verschueren, A and Ranjeva, JP and Guye, M and Attarian, S and Zaaraoui, W and Grapperon, AM}, title = {Association between brain and upper cervical spinal cord atrophy assessed by MRI and disease aggressiveness in amyotrophic lateral sclerosis.}, journal = {Neuroradiology}, volume = {65}, number = {9}, pages = {1395-1403}, pmid = {37458788}, issn = {1432-1920}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnostic imaging/pathology ; *Cervical Cord/diagnostic imaging ; Magnetic Resonance Imaging ; *White Matter ; Atrophy/pathology ; }, abstract = {PURPOSE: To study the relative contributions of brain and upper cervical spinal cord compartmental atrophy to disease aggressiveness in amyotrophic lateral sclerosis (ALS).

METHODS: Twenty-nine ALS patients and 24 age- and gender-matched healthy controls (HC) were recruited. Disease duration and the Revised-ALS Functional Rating Scale (ALSFRS-R) at baseline, 3- and 6-months follow-up were assessed. Patients were clinically differentiated into fast (n=13) and slow (n=16) progressors according to their ALSFRS-R progression rate. Brain grey (GM) and white matter, brainstem sub-structures volumes and spinal cord cross-sectional area (SC-CSA) at C1-C2 vertebral levels were measured from a 3D-T1-weighted MRI.

RESULTS: Fast progressors showed significant GM, medulla oblongata and SC atrophy compared to HC (p<0.001, p=0.013 and p=0.008) and significant GM atrophy compared to slow progressors (p=0.008). GM volume correlated with the ALSFRS-R progression rate (Rho/p=-0.487/0.007), the ALSFRS-R at 3-months (Rho/p=0.622/0.002), and ALSFRS-R at 6-months (Rho/p=0.407/0.039). Medulla oblongata volume and SC-CSA correlated with the ALSFRS-R at 3-months (Rho/p=0.510/0.015 and Rho/p=0.479/0.024). MRI measures showed high performance to discriminate between fast and slow progressors.

CONCLUSION: Our study suggests an association between compartmental atrophy and disease aggressiveness. This result is consistent with the combination of upper and lower motor neuron degeneration as the main driver of disease worsening and severity in ALS. Our study highlights the potential of brain and spinal cord atrophy measured by MRI as biomarker of disease aggressiveness signature.}, } @article {pmid37458559, year = {2023}, author = {Desnuelle, C}, title = {[Living with… amyotrophic lateral].}, journal = {La Revue du praticien}, volume = {73}, number = {6}, pages = {659-660}, pmid = {37458559}, issn = {2101-017X}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/therapy ; }, } @article {pmid37457842, year = {2023}, author = {Mavridis, IN and Pyrgelis, ES}, title = {Nucleus accumbens changes in amyotrophic lateral sclerosis.}, journal = {American journal of neurodegenerative disease}, volume = {12}, number = {3}, pages = {85-88}, pmid = {37457842}, issn = {2165-591X}, abstract = {Amyotrophic lateral sclerosis (ALS), a representative example of motor neuron disease, is a progressive and fatal neurodegenerative disorder. The nucleus accumbens (NA) is the ventral striatum's main part and is considered as a modulator of the human brain's reward network. The purpose of this article is to review the current knowledge regarding NA changes in ALS patients. The NA involvement in ALS includes volumetric, cellular and molecular changes. There are recent imaging and pathological studies revealing NA atrophy in ALS, a finding which seems to be related to neuronal loss and protein deposition in this area. The clinical significance of NA atrophy in these patients is not currently fully understood. Perhaps it could be correlated with apathy, behavioral disturbances and cognitive impairment that ALS patients sometimes manifest.}, } @article {pmid37456581, year = {2023}, author = {Giovannelli, L and Bari, E and Jommi, C and Tartara, F and Armocida, D and Garbossa, D and Cofano, F and Torre, ML and Segale, L}, title = {Mesenchymal stem cell secretome and extracellular vesicles for neurodegenerative diseases: Risk-benefit profile and next steps for the market access.}, journal = {Bioactive materials}, volume = {29}, number = {}, pages = {16-35}, pmid = {37456581}, issn = {2452-199X}, abstract = {Neurodegenerative diseases represent a growing burden on healthcare systems worldwide. Mesenchymal stem cells (MSCs) have shown promise as a potential therapy due to their neuroregenerative, neuroprotective, and immunomodulatory properties, which are, however, linked to the bioactive substances they release, collectively known as secretome. This paper provides an overview of the most recent research on the safety and efficacy of MSC-derived secretome and extracellular vesicles (EVs) in clinical (if available) and preclinical models of Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis, Huntington's disease, acute ischemic stroke, and spinal cord injury. The article explores the biologically active substances within MSC-secretome/EVs, the mechanisms responsible for the observed therapeutic effects, and the strategies that may be used to optimize MSC-secretome/EVs production based on specific therapeutic needs. The review concludes with a critical discussion of current clinical trials and a perspective on potential future directions in translating MSC-secretome and EVs into the clinic, specifically regarding how to address the challenges associated with their pharmaceutical manufacturing, including scalability, batch-to-batch consistency, adherence to Good Manufacturing Practices (GMP) guidelines, formulation, and storage, along with quality controls, access to the market and relative costs, value for money and impact on total expenditure.}, } @article {pmid37456074, year = {2023}, author = {Li, Y and Xie, D and Wang, Y and Jin, S and Zhou, K and Zhang, Z and Li, W and Zhang, W and Mu, X and Yan, G}, title = {Individual tree segmentation of airborne and UAV LiDAR point clouds based on the watershed and optimized connection center evolution clustering.}, journal = {Ecology and evolution}, volume = {13}, number = {7}, pages = {e10297}, pmid = {37456074}, issn = {2045-7758}, abstract = {Light detection and ranging (LiDAR) data can provide 3D structural information of objects and are ideal for extracting individual tree parameters, and individual tree segmentation (ITS) is a vital step for this purpose. Various ITS methods have been emerging from airborne LiDAR scanning (ALS) or unmanned aerial vehicle LiDAR scanning (ULS) data. Here, we propose a new individual tree segmentation method, which couples the classical and efficient watershed algorithm (WS) and the newly developed connection center evolution (CCE) clustering algorithm in pattern recognition. The CCE is first used in ITS and comprehensively optimized by considering tree structure and point cloud characteristics. Firstly, the amount of data is greatly reduced by mean shift voxelization. Then, the optimal clustering scale is automatically determined by the shapes in the projection of three different directions. We select five forest plots in Saihanba, China and 14 public plots in Alpine region, Europe with ULS or ALS point cloud densities from 11 to 3295 pts/m[2]. Eleven ITS methods were used for comparison. The accuracy of tree top detection and tree height extraction is estimated by five and two metrics, respectively. The results show that the matching rate (R match) of tree tops is up to 0.92, the coefficient of determination (R [2]) of tree height estimation is up to .94, and the minimum root mean square error (RMSE) is 0.6 m. Our method outperforms the other methods especially in the broadleaf forests plot on slopes, where the five evaluation metrics for tree top detection outperformed the other algorithms by at least 11% on average. Our ITS method is both robust and efficient and has the potential to be used especially in coniferous forests to extract the structural parameters of individual trees for forest management, carbon stock estimation, and habitat mapping.}, } @article {pmid37454169, year = {2023}, author = {Antoniani, F and Cimino, M and Mediani, L and Vinet, J and Verde, EM and Secco, V and Yamoah, A and Tripathi, P and Aronica, E and Cicardi, ME and Trotti, D and Sterneckert, J and Goswami, A and Carra, S}, title = {Loss of PML nuclear bodies in familial amyotrophic lateral sclerosis-frontotemporal dementia.}, journal = {Cell death discovery}, volume = {9}, number = {1}, pages = {248}, pmid = {37454169}, issn = {2058-7716}, support = {DFG FZT 111 and DFG EXC 168//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; WE 1406/16-1//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; }, abstract = {Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD) are two neurodegenerative disorders that share genetic causes and pathogenic mechanisms. The critical genetic players of ALS and FTD are the TARDBP, FUS and C9orf72 genes, whose protein products, TDP-43, FUS and the C9orf72-dipeptide repeat proteins, accumulate in form of cytoplasmic inclusions. The majority of the studies focus on the understanding of how cells control TDP-43 and FUS aggregation in the cytoplasm, overlooking how dysfunctions occurring at the nuclear level may influence the maintenance of protein solubility outside of the nucleus. However, protein quality control (PQC) systems that maintain protein homeostasis comprise a cytoplasmic and a nuclear arm that are interconnected and share key players. It is thus conceivable that impairment of the nuclear arm of the PQC may have a negative impact on the cytoplasmic arm of the PQC, contributing to the formation of the cytoplasmic pathological inclusions. Here we focused on two stress-inducible condensates that act as transient deposition sites for misfolding-prone proteins: Promyelocytic leukemia protein (PML) nuclear bodies (PML-NBs) and cytoplasmic stress granules (SGs). Upon stress, PML-NBs compartmentalize misfolded proteins, including defective ribosomal products (DRiPs), and recruit chaperones and proteasomes to promote their nuclear clearance. SGs transiently sequester aggregation-prone RNA-binding proteins linked to ALS-FTD and mRNAs to attenuate their translation. We report that PML assembly is impaired in the human brain and spinal cord of familial C9orf72 and FUS ALS-FTD cases. We also show that defective PML-NB assembly impairs the compartmentalization of DRiPs in the nucleus, leading to their accumulation inside cytoplasmic SGs, negatively influencing SG dynamics. Although it is currently unclear what causes the decrease of PML-NBs in ALS-FTD, our data highlight the existence of a cross-talk between the cytoplasmic and nuclear PQC systems, whose alteration can contribute to SG accumulation and cytoplasmic protein aggregation in ALS-FTD.}, } @article {pmid37452624, year = {2023}, author = {Asakawa, K and Handa, H and Kawakami, K}, title = {Dysregulated TDP-43 proteostasis perturbs excitability of spinal motor neurons during brainstem-mediated fictive locomotion in zebrafish.}, journal = {Development, growth & differentiation}, volume = {65}, number = {8}, pages = {446-452}, pmid = {37452624}, issn = {1440-169X}, support = {//Daiichi-Sankyo Foundation of Life Science/ ; JP23gm6410011h0003//Japan Agency for Medical Research and Development/ ; JP16K07045//Japan Society for the Promotion of Science/ ; JP19K06933//Japan Society for the Promotion of Science/ ; JP21H02463//Japan Society for the Promotion of Science/ ; JP22H02958//Japan Society for the Promotion of Science/ ; JP23H04266//Japan Society for the Promotion of Science/ ; //Nakabayashi Trust For ALS Research/ ; //National BioResource Project (NBRP)/ ; //Takeda Science Foundation/ ; //The Kato Memorial Trust For Nambyo Research/ ; }, mesh = {Animals ; Humans ; *Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology ; Zebrafish/metabolism ; Calcium/metabolism ; Proteostasis ; Motor Neurons/metabolism/pathology ; Spinal Cord ; DNA-Binding Proteins/genetics/metabolism ; }, abstract = {Spinal motor neurons (SMNs) are the primary target of degeneration in amyotrophic lateral sclerosis (ALS). Degenerating motor neurons accumulate cytoplasmic TAR DNA-binding protein 43 (TDP-43) aggregates in most ALS cases. This SMN pathology can occur without mutation in the coding sequence of the TDP-43-encoding gene, TARDBP. Whether and how wild-type TDP-43 drives pathological changes in SMNs in vivo remains largely unexplored. In this study, we develop a two-photon calcium imaging setup in which tactile-evoked neural responses of motor neurons in the brainstem and spinal cord can be monitored using the calcium indicator GCaMP. We devise a piezo-assisted tactile stimulator that reproducibly evokes a brainstem descending neuron upon tactile stimulation of the head. A direct comparison between caudal primary motor neurons (CaPs) with or without TDP-43 overexpression in contiguous spinal segments demonstrates that CaPs overexpressing TDP-43 display attenuated Ca[2+] transients during fictive escape locomotion evoked by the tactile stimulation. These results show that excessive amounts of TDP-43 protein reduce the neuronal excitability of SMNs and potentially contribute to asymptomatic pathological lesions of SMNs and movement disorders in patients with ALS.}, } @article {pmid37452450, year = {2023}, author = {Boyle, J and Wheeler, DC and Naum, R and Burke Brockenbrough, P and Gebhardt, M and Smith, L and Harrell, T and Stewart, D and Gwathmey, K}, title = {Analysis of the spatial distribution of amyotrophic lateral sclerosis in Virginia.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {}, number = {}, pages = {1-9}, doi = {10.1080/21678421.2023.2236653}, pmid = {37452450}, issn = {2167-9223}, abstract = {Objective: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder that is usually fatal. Environmental exposures have been posited in the etiology of ALS, but few studies have modeled the spatial risk of ALS over large geographic areas. In this paper, our goal was to analyze the spatial distribution of ALS in Virginia and identify any areas with significantly elevated risk using Virginia ALS Association administrative data. Methods: We used Bayesian hierarchical spatial regression models to estimate the relative risk for ALS in Virginia census tracts, adjusting for several covariates posited to be associated with the disease. We used an intrinsic conditional autoregressive prior to allow for spatial correlation in the risk estimates and stabilize estimates over space. Results: Considerable variation in ALS risk existed across Virginia, with greater relative risk found in the central and western parts of the state. We identified significantly elevated relative risk in a number of census tracts. In particular, Henrico, Albemarle, and Botetourt counties all contained at least four census tracts with significantly elevated risk. Conclusions: We identified several areas with significantly elevated ALS risk across Virginia census tracts. These results can inform future studies of potential environmental triggers for the disease, whose etiology is still being understood.}, } @article {pmid37451615, year = {2023}, author = {Yen, H and Yen, H and Huang, CH and Huang, IH and Hung, WK and Su, HJ and Tai, CC and Haw, WWY and Flohr, C and Yiu, ZZN and Chi, CC}, title = {Systematic Review and Critical Appraisal of Urticaria Clinical Practice Guidelines: A Global Guidelines in Dermatology Mapping Project (GUIDEMAP).}, journal = {The journal of allergy and clinical immunology. In practice}, volume = {11}, number = {10}, pages = {3213-3220.e11}, doi = {10.1016/j.jaip.2023.07.002}, pmid = {37451615}, issn = {2213-2201}, mesh = {Humans ; Australia ; Databases, Factual ; *Dermatology ; Stakeholder Participation ; *Urticaria/diagnosis/therapy ; Practice Guidelines as Topic ; }, abstract = {BACKGROUND: Management of urticaria can be optimized with clinical practice guidelines (CPGs). However, the quality of recent urticaria CPGs remains unclear.

OBJECTIVE: To identify and appraise urticaria CPGs worldwide published in the last 5 years.

METHODS: A search for relevant urticaria CPGs was conducted between January 1, 2017, and May 31, 2022, using the following databases: MEDLINE, Embase, National Institute for Health and Care Excellence (NICE) Evidence Search, Guidelines International Network, ECRI Guidelines Trust, Australian Clinical Practice Guidelines, Trip Medical Database, and DynaMed. The included CPGs were critically appraised using the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument, Lenzer et al's red flags, and the Institute of Medicine (IOM) criteria of trustworthiness.

RESULTS: We included 21 urticaria CPGs. Most guidelines reviewed treatment recommendations of chronic spontaneous urticaria. The majority of guidelines were from European and Asian countries with high and high-middle sociodemographic index, written in English, and openly accessible. Seventeen guidelines (81%) had at least 1 AGREE II domain rated poor quality. Applicability, rigor of development, and stakeholder involvement were the 3 AGREE II domains that scored the lowest across guidelines. Appraisal with Lenzer et al's red flags showed that 18 guidelines (86%) raised at least 1 red flag indicating potential bias. The top 3 domains raising red flags were: no inclusion of nonphysician experts/patient representative/community stakeholders, no or limited involvement of a methodologist in the evaluation of evidence, and lack of external review. Based on IOM's criteria of trustworthiness, 20 guidelines (95%) had 1 or more criteria that did not meet best practice standards. The 3 domains with the highest number of best practice standards not met were updating procedures, rating strength of recommendations, and external review. Guidelines scored highest for the AGREE II domains of defining scope and purpose and clarity of presentation, and had the most fully met IOM's best practice standard for articulation of recommendations. However, only 1 urticaria CPG by NICE was identified as rigorously developed across all 3 appraisal tools.

CONCLUSIONS: The quality of urticaria CPGs in the last 5 years varied widely. Only the NICE urticaria guideline consistently demonstrated excellent quality, high trustworthiness, and low risk of bias. Use of a rigorous framework to rate certainty of evidence and grade strength of recommendation, involvement of methodologists, stakeholder engagement with external review, and clear guidance for updating can help improve the quality of future CPGs.}, } @article {pmid37451236, year = {2023}, author = {Koike, Y and Pickles, S and Ayuso, VE and Jansen-West, K and Qi, YA and Li, Z and Daughrity, LM and Yue, M and Zhang, YJ and Cook, CN and Dickson, DW and Ward, M and Petrucelli, L and Prudencio, M}, title = {Correction: TDP-43 and other hnRNPs regulate cryptic exon inclusion of a key ALS/FTD risk gene, UNC13A.}, journal = {PLoS biology}, volume = {21}, number = {7}, pages = {e3002228}, pmid = {37451236}, issn = {1545-7885}, abstract = {[This corrects the article DOI: 10.1371/journal.pbio.3002028.].}, } @article {pmid37450673, year = {2023}, author = {Mushtaq, U}, title = {EP1 receptor: Devil in emperors coat.}, journal = {Journal of cellular biochemistry}, volume = {124}, number = {8}, pages = {1105-1114}, doi = {10.1002/jcb.30436}, pmid = {37450673}, issn = {1097-4644}, mesh = {Receptors, Prostaglandin E, EP1 Subtype/genetics ; *Signal Transduction/physiology ; *Protein Kinase C/metabolism ; }, abstract = {EP1 receptor belongs to prostanoid receptors and is activated by prostaglandin E2. The receptor performs contrasting functions in central nervous system (CNS) and other tissues. Although the receptor is neurotoxic and proapoptotic in CNS, it has also been reported to act in an antiapoptotic manner by modulating cell survival, proliferation, invasion, and migration in different types of cancers. The receptor mediates its neurotoxic effects by increasing cytosolic Ca[2+] levels, leading to the activation of its downstream target, protein kinase C, in different neurological disorders including Alzheimer's disease, Parkinson's disease, stroke, amyotrophic lateral sclerosis, and epilepsy. Antagonists ONO-8713, SC51089, and SC51322 against EP1 receptor ameliorate the neurotoxic effect by attenuating the neuroinflammation. The receptor also shows increased expression in different types of cancers and has been found to activate different signaling pathways, which lead to the development, progression, and metastasis of different cancers. The receptor stimulates the cell survival pathway by phosphorylating the AKT and PTEN (phosphatase and tensin homolog deleted on chromosome 10) signaling pathways. Although there are limited studies about this receptor and not a single clinical trial has been targeting the EP1 receptor for different neurological disorders or cancer, the receptor is appearing as a potential candidate for therapeutic targets. The aim of this article is to review the recent progress in understanding the pathogenic roles of EP1 receptors in different pathological conditions.}, } @article {pmid37450615, year = {2024}, author = {Karasz, A and Nemiroff, S and Joo, P and Blanco, I and Fishman, AY and Kelly, MS and Henick, SM and Lambros, M and Burton, WB}, title = {A Sense of Belonging: Perceptions of the Medical School Learning Environment among URM and Non-URM Students.}, journal = {Teaching and learning in medicine}, volume = {36}, number = {5}, pages = {566-576}, doi = {10.1080/10401334.2023.2232347}, pmid = {37450615}, issn = {1532-8015}, mesh = {Humans ; *Students, Medical/psychology/statistics & numerical data ; New York City ; Female ; *Schools, Medical ; Male ; Minority Groups/psychology/statistics & numerical data ; Education, Medical, Undergraduate ; Perception ; Adult ; }, abstract = {Approach: Using Gruppen et al's model, this study investigated experiences of the LE from the perspectives of both URM and non-URM students at a medical school in New York City. In examining experiences of the organizational, social, and physical domains of the LE, we sought to explore the symbolic and experiential links across domains and identify concrete needs for improvement. Findings: Institutional structures and policies, features of the built environment, and social relationships that put learning first and generated a sense of community were highly valued. Although both URM and non-URM students shared many perceptions and experiences, URM students expressed heightened vulnerability to the experiences of devaluation and exclusion. Insights: All participants in the study greatly appreciated aspects of the LE that made them feel like valued members of the community. Medical schools should approach the task of improving the LE for URM students using a comprehensive, multi-dimensional approach.}, } @article {pmid37450566, year = {2023}, author = {Rifai, OM and O'Shaughnessy, J and Dando, OR and Munro, AF and Sewell, MDE and Abrahams, S and Waldron, FM and Sibley, CR and Gregory, JM}, title = {Distinct neuroinflammatory signatures exist across genetic and sporadic amyotrophic lateral sclerosis cohorts.}, journal = {Brain : a journal of neurology}, volume = {146}, number = {12}, pages = {5124-5138}, pmid = {37450566}, issn = {1460-2156}, support = {/WT_/Wellcome Trust/United Kingdom ; R01 NS127186/NS/NINDS NIH HHS/United States ; 5-R01-NS127186-02/GF/NIH HHS/United States ; 108890/Z/15/Z/WT_/Wellcome Trust/United Kingdom ; }, mesh = {*Amyotrophic Lateral Sclerosis/pathology ; Brain-Derived Neurotrophic Factor/genetics ; NF-kappa B ; *Neurodegenerative Diseases/genetics ; Dystonic Disorders ; Humans ; DNA Repeat Expansion ; C9orf72 Protein/genetics ; *Frontotemporal Dementia/genetics ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive loss of upper and lower motor neurons. ALS is on a pathogenetic disease spectrum with frontotemporal dementia, referred to as ALS-frontotemporal spectrum disorder (ALS-FTSD). For mutations associated with ALS-FTSD, such as the C9orf72 hexanucleotide repeat expansion, the molecular factors associated with heterogeneity along this spectrum require further characterization. Here, using a targeted NanoString molecular barcoding approach, we interrogate neuroinflammatory dysregulation and heterogeneity at the level of gene expression in post-mortem motor cortex tissue from a cohort of clinically heterogeneous C9-ALS-FTSD cases. We identified 20 dysregulated genes in C9-ALS-FTSD, with enrichment of microglial and inflammatory response gene sets. Two genes with significant correlations to available clinical metrics were selected for validation: FKBP5, a correlate of cognitive function, and brain-derived neurotrophic factor (BDNF), a correlate of disease duration. FKBP5 and its signalling partner, NF-κB, appeared to have a cell type-specific staining distribution, with activated (i.e. nuclear) NF-κB immunoreactivity in C9-ALS-FTSD. Expression of BDNF, a correlate of disease duration, was confirmed to be higher in individuals with long compared to short disease duration using BaseScope™ in situ hybridization. Our analyses also revealed two distinct neuroinflammatory panel signatures (NPS), NPS1 and NPS2, delineated by the direction of expression of proinflammatory, axonal transport and synaptic signalling pathways. We compared NPS between C9-ALS-FTSD cases and those from sporadic ALS and SOD1-ALS cohorts and identified NPS1 and NPS2 across all cohorts. Moreover, a subset of NPS was also able to separate publicly available RNA sequencing data from independent C9-ALS and sporadic ALS cohorts into two inflammatory subgroups. Importantly, NPS subgroups did not clearly segregate with available demographic, genetic, clinical or pathological features, highlighting the value of molecular stratification in clinical trials for inflammatory subgroup identification. Our findings thus underscore the importance of tailoring therapeutic approaches based on distinct molecular signatures that exist between and within ALS-FTSD cohorts.}, } @article {pmid37450246, year = {2023}, author = {Candelise, N and Caissutti, D and Zenuni, H and Nesci, V and Scaricamazza, S and Salvatori, I and Spinello, Z and Mattei, V and Garofalo, T and Ferri, A and Valle, C and Misasi, R}, title = {Different Chronic Stress Paradigms Converge on Endogenous TDP43 Cleavage and Aggregation.}, journal = {Molecular neurobiology}, volume = {60}, number = {11}, pages = {6346-6361}, pmid = {37450246}, issn = {1559-1182}, support = {Post-doctoral Fellowship 2021 - anno 2021//Fondazione Umberto Veronesi/ ; CUP B89J22001910007//Fondazione Cassa di Risparmio di Pistoia e Pescia/ ; PRIN 20109MXHNR//Ministero dell'Università e della Ricerca/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics ; Cell Line ; Cytoplasm/metabolism ; *DNA-Binding Proteins/metabolism ; Neuroblastoma/metabolism ; TDP-43 Proteinopathies/metabolism ; }, abstract = {The TAR-DNA binding protein (TDP43) is a nuclear protein whose cytoplasmic inclusions are hallmarks of Amyotrophic Lateral Sclerosis (ALS). Acute stress in cells causes TDP43 mobilization to the cytoplasm and its aggregation through different routes. Although acute stress elicits a strong phenotype, is far from recapitulating the years-long aggregation process. We applied different chronic stress protocols and described TDP43 aggregation in a human neuroblastoma cell line by combining solubility assays, thioflavin-based microscopy and flow cytometry. This approach allowed us to detect, for the first time to our knowledge in vitro, the formation of 25 kDa C-terminal fragment of TDP43, a pathogenic hallmark of ALS. Our results indicate that chronic stress, compared to the more common acute stress paradigm, better recapitulates the cell biology of TDP43 proteinopathies. Moreover, we optimized a protocol for the detection of bona fide prions in living cells, suggesting that TDP43 may form amyloids as a stress response.}, } @article {pmid37450244, year = {2023}, author = {Dubowsky, M and Theunissen, F and Carr, JM and Rogers, ML}, title = {The Molecular Link Between TDP-43, Endogenous Retroviruses and Inflammatory Neurodegeneration in Amyotrophic Lateral Sclerosis: a Potential Target for Triumeq, an Antiretroviral Therapy.}, journal = {Molecular neurobiology}, volume = {60}, number = {11}, pages = {6330-6345}, pmid = {37450244}, issn = {1559-1182}, support = {1950//Motor Neurone Disease Australia/ ; 1950//Andrew Butcher Grant/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics ; *Endogenous Retroviruses ; *Motor Neuron Disease/pathology ; Motor Neurons/metabolism ; DNA-Binding Proteins/metabolism ; *HIV Infections/pathology ; }, abstract = {Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND), is a progressive neurological disorder, characterised by the death of upper and lower motor neurons. The aetiology of ALS remains unknown, and treatment options are limited. Endogenous retroviruses (ERVs), specifically human endogenous retrovirus type K (HERV-K), have been proposed to be involved in the propagation of neurodegeneration in ALS. ERVs are genomic remnants of ancient viral infection events, with most being inactive and not retaining the capacity to encode a fully infectious virus. However, some ERVs retain the ability to be activated and transcribed, and ERV transcripts have been found to be elevated within the brain tissue of MND patients. A hallmark of ALS pathology is altered localisation of the transactive response (TAR) DNA binding protein 43 kDa (TDP-43), which is normally found within the nucleus of neuronal and glial cells and is involved in RNA regulation. In ALS, TDP-43 aggregates within the cytoplasm and facilitates neurodegeneration. The involvement of ERVs in ALS pathology is thought to occur through TDP-43 and neuroinflammatory mediators. In this review, the proposed involvement of TDP-43, HERV-K and immune regulators on the onset and progression of ALS will be discussed. Furthermore, the evidence supporting a therapy based on targeting ERVs in ALS will be reviewed.}, } @article {pmid37449847, year = {2023}, author = {Wang, J and Mao, Y and McGarry, B and Cai, S and Temkin-Greener, H}, title = {Assisted living or nursing home: Who is moving in?.}, journal = {Journal of the American Geriatrics Society}, volume = {71}, number = {11}, pages = {3480-3488}, pmid = {37449847}, issn = {1532-5415}, support = {R01 HS026893/HS/AHRQ HHS/United States ; 1R01HS026893/AG/NIA NIH HHS/United States ; }, mesh = {Humans ; Male ; Aged ; United States ; *Skilled Nursing Facilities ; Retrospective Studies ; *Medicare ; Nursing Homes ; Hospitalization ; Patient Discharge ; }, abstract = {BACKGROUND: Despite the rapid growth of assisted living (AL) communities and the increasing similarity between AL and nursing home (NH) populations, little is known about the characteristics of older adults at the time of AL admission and how these characteristics compare to individuals newly admitted to NH from the community. This study examined the individual, facility, and geographic factors associated with new AL admission.

METHODS: This retrospective descriptive study used data from the national Medicare enrollment and claims datasets, the Minimum Data Set, and the Medicare Provider Analysis and Review. The study cohort included 158,124 Medicare beneficiaries newly admitted to ALs and 715,261 newly admitted to NHs during 10/2017-10/2019. Multinomial logistic regression analysis and logistic regression analysis were conducted to examine factors associated with new admissions.

RESULTS: Demographic, socioeconomic, and health service use characteristics were associated with new admission to long-term care. Specifically, Medicare fee-for-service beneficiaries, those age 75 years and older, male, having one skilled nursing facility (SNF) stay or any hospital stay in the past 6 months are more likely to be newly admitted to AL, whereas those who are dually eligible, racial/ethnic minorities, and having two or more SNF stays in the past 6 months are more likely to be admitted to an NH.

CONCLUSION: There are substantial differences between individuals who are newly admitted from the community to AL versus those to NH.}, } @article {pmid37448088, year = {2023}, author = {Xu, J and Huang, Z and Liu, L and Li, X and Wei, K}, title = {Eye-Gaze Controlled Wheelchair Based on Deep Learning.}, journal = {Sensors (Basel, Switzerland)}, volume = {23}, number = {13}, pages = {}, pmid = {37448088}, issn = {1424-8220}, mesh = {Humans ; *Deep Learning ; *Wheelchairs ; Fixation, Ocular ; Movement ; Motion ; }, abstract = {In this paper, we design a technologically intelligent wheelchair with eye-movement control for patients with ALS in a natural environment. The system consists of an electric wheelchair, a vision system, a two-dimensional robotic arm, and a main control system. The smart wheelchair obtains the eye image of the controller through a monocular camera and uses deep learning and an attention mechanism to calculate the eye-movement direction. In addition, starting from the relationship between the trajectory of the joystick and the wheelchair speed, we establish a motion acceleration model of the smart wheelchair, which reduces the sudden acceleration of the smart wheelchair during rapid motion and improves the smoothness of the motion of the smart wheelchair. The lightweight eye-movement recognition model is transplanted into an embedded AI controller. The test results show that the accuracy of eye-movement direction recognition is 98.49%, the wheelchair movement speed is up to 1 m/s, and the movement trajectory is smooth, without sudden changes.}, } @article {pmid37446372, year = {2023}, author = {Alarcan, H and Vourc'h, P and Berton, L and Benz-De Bretagne, I and Piver, E and Andres, CR and Corcia, P and Veyrat-Durebex, C and Blasco, H}, title = {Implication of Central Nervous System Barrier Impairment in Amyotrophic Lateral Sclerosis: Gender-Related Difference in Patients.}, journal = {International journal of molecular sciences}, volume = {24}, number = {13}, pages = {}, pmid = {37446372}, issn = {1422-0067}, mesh = {Female ; Humans ; Male ; *Amyotrophic Lateral Sclerosis/genetics ; Retrospective Studies ; Sex Factors ; Delayed Diagnosis ; Central Nervous System ; }, abstract = {Central nervous system (CNS) barrier impairment has been reported in amyotrophic lateral sclerosis (ALS), highlighting its potential significance in the disease. In this context, we aim to shed light on its involvement in the disease, by determining albumin quotient (QAlb) at the time of diagnosis of ALS in a large cohort of patients. Patients from the university hospital of Tours (n = 307) were included in this monocentric, retrospective study. In total, 92 patients (30%) had elevated QAlb levels. This percentage was higher in males (43%) than in females (15%). Interestingly, QAlb was not associated with age of onset, age at sampling or diagnostic delay. However, we found an association with ALS functional rating scale-revised (ALSFRS-r) at diagnosis but this was significant only in males. The QAlb levels were not linked to the presence of a pathogenic mutation. Finally, we performed a multivariate survival analysis and found that QAlb was significantly associated with survival in male patients (HR = 2.3, 95% CI = 1.2-4.3, p = 0.009). A longitudinal evaluation of markers of barrier impairment, in combination with inflammatory biomarkers, could give insight into the involvement of CNS barrier impairment in the pathogenesis of the disease. The gender difference might guide the development of new drugs and help personalise the treatment of ALS.}, } @article {pmid37445986, year = {2023}, author = {Ciurea, AV and Mohan, AG and Covache-Busuioc, RA and Costin, HP and Glavan, LA and Corlatescu, AD and Saceleanu, VM}, title = {Unraveling Molecular and Genetic Insights into Neurodegenerative Diseases: Advances in Understanding Alzheimer's, Parkinson's, and Huntington's Diseases and Amyotrophic Lateral Sclerosis.}, journal = {International journal of molecular sciences}, volume = {24}, number = {13}, pages = {}, pmid = {37445986}, issn = {1422-0067}, mesh = {Humans ; *Neurodegenerative Diseases/genetics ; *Huntington Disease/genetics ; *Alzheimer Disease/genetics ; *Parkinson Disease/genetics ; *Amyotrophic Lateral Sclerosis/genetics ; }, abstract = {Neurodegenerative diseases are, according to recent studies, one of the main causes of disability and death worldwide. Interest in molecular genetics has started to experience exponential growth thanks to numerous advancements in technology, shifts in the understanding of the disease as a phenomenon, and the change in the perspective regarding gene editing and the advantages of this action. The aim of this paper is to analyze the newest approaches in genetics and molecular sciences regarding four of the most important neurodegenerative disorders: Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. We intend through this review to focus on the newest treatment, diagnosis, and predictions regarding this large group of diseases, in order to obtain a more accurate analysis and to identify the emerging signs that could lead to a better outcome in order to increase both the quality and the life span of the patient. Moreover, this review could provide evidence of future possible novel therapies that target the specific genes and that could be useful to be taken into consideration when the classical approaches fail to shed light.}, } @article {pmid37445890, year = {2023}, author = {Kousparou, C and Fyrilla, M and Stephanou, A and Patrikios, I}, title = {DHA/EPA (Omega-3) and LA/GLA (Omega-6) as Bioactive Molecules in Neurodegenerative Diseases.}, journal = {International journal of molecular sciences}, volume = {24}, number = {13}, pages = {}, pmid = {37445890}, issn = {1422-0067}, mesh = {Humans ; Eicosapentaenoic Acid/pharmacology ; Docosahexaenoic Acids/therapeutic use/metabolism ; *Neurodegenerative Diseases/drug therapy ; *Fatty Acids, Omega-3/therapeutic use ; Fatty Acids, Unsaturated/metabolism ; Arachidonic Acid/metabolism ; Linoleic Acids ; Inflammation/drug therapy ; }, abstract = {Neurodegenerative diseases are characterized by neuroinflammation, neuronal depletion and oxidative stress. They coincide with subtle chronic or flaring inflammation, sometimes escalating with infiltrations of the immune system cells in the inflamed parts causing mild to severe or even lethal damage. Thus, neurodegenerative diseases show all features of autoimmune diseases. Prevalence of neurodegenerative diseases has dramatically increased in recent decades and unfortunately, the therapeutic efficacy and safety profile of available drugs is moderate. The beneficial effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) polyunsaturated fatty acids (omega-3 PUFAs) are nowadays highlighted by a plethora of studies. They play a role in suppression of inflammation, gene expression, cellular membrane fluidity/permeability, immune functionality and intracellular/exocellular signaling. The role of omega-6 polyunsaturated fatty acids, such as linoleic acid (LA), gamma linolenic acid (GLA), and arachidonic acid (AA), on neuroprotection is controversial, as some of these agents, specifically AA, are proinflammatory, whilst current data suggest that they may have neuroprotective properties as well. This review provides an overview of the existing recent clinical studies with respect to the role of omega-3 and omega-6 PUFAs as therapeutic agents in chronic, inflammatory, autoimmune neurodegenerative diseases as well as the dosages and the period used for testing.}, } @article {pmid37443797, year = {2023}, author = {Afonso, GJM and Cavaleiro, C and Valero, J and Mota, SI and Ferreiro, E}, title = {Recent Advances in Extracellular Vesicles in Amyotrophic Lateral Sclerosis and Emergent Perspectives.}, journal = {Cells}, volume = {12}, number = {13}, pages = {}, pmid = {37443797}, issn = {2073-4409}, support = {PTDC/BTM-ORG/0055/2021, UIDB/04539/2020, UIDP/04539/2020, LA/P/0058/2020, 2022.13281.BD, DL57/2016/CP1448/CT0027, CEECIND/00322/2017, 2022.00011.CEECIND.//Fundação para a Ciência e Tecnologia/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis ; *Neurodegenerative Diseases ; *Extracellular Vesicles ; Motor Neurons ; *Exosomes ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a severe and incurable neurodegenerative disease characterized by the progressive death of motor neurons, leading to paralysis and death. It is a rare disease characterized by high patient-to-patient heterogeneity, which makes its study arduous and complex. Extracellular vesicles (EVs) have emerged as important players in the development of ALS. Thus, ALS phenotype-expressing cells can spread their abnormal bioactive cargo through the secretion of EVs, even in distant tissues. Importantly, owing to their nature and composition, EVs' formation and cargo can be exploited for better comprehension of this elusive disease and identification of novel biomarkers, as well as for potential therapeutic applications, such as those based on stem cell-derived exosomes. This review highlights recent advances in the identification of the role of EVs in ALS etiopathology and how EVs can be promising new therapeutic strategies.}, } @article {pmid37443723, year = {2023}, author = {Spalloni, A and de Stefano, S and Gimenez, J and Greco, V and Mercuri, NB and Chiurchiù, V and Longone, P}, title = {The Ying and Yang of Hydrogen Sulfide as a Paracrine/Autocrine Agent in Neurodegeneration: Focus on Amyotrophic Lateral Sclerosis.}, journal = {Cells}, volume = {12}, number = {13}, pages = {}, pmid = {37443723}, issn = {2073-4409}, support = {RF-2018-12365509//Italian Ministry of Health/ ; Ricerca Corrente (Linea di Ricerca 2)//Governo Italiano/ ; }, mesh = {Humans ; *Hydrogen Sulfide ; *Neurodegenerative Diseases ; *Amyotrophic Lateral Sclerosis ; Central Nervous System ; Nitric Oxide ; }, abstract = {Ever since its presence was reported in the brain, the nature and role of hydrogen sulfide (H2S) in the Central Nervous System (CNS) have changed. Consequently, H2S has been elected as the third gas transmitter, along with carbon monoxide and nitric oxide, and a number of studies have focused on its neuromodulatory and protectant functions in physiological conditions. The research on H2S has highlighted its many facets in the periphery and in the CNS, and its role as a double-faced compound, switching from protective to toxic depending on its concentration. In this review, we will focus on the bell-shaped nature of H2S as an angiogenic factor and as a molecule released by glial cells (mainly astrocytes) and non-neuronal cells acting on the surrounding environment (paracrine) or on the releasing cells themselves (autocrine). Finally, we will discuss its role in Amyotrophic Lateral Sclerosis, a paradigm of a neurodegenerative disease.}, } @article {pmid37442650, year = {2024}, author = {Lopez-Garcia, YK and Valdez-Carrizales, M and Nuñez-Zuno, JA and Apodaca-Chávez, E and Rangel-Patiño, J and Demichelis-Gómez, R}, title = {Are delays in diagnosis and treatment of acute leukemia in a middle-income country associated with poor outcomes? A retrospective cohort study.}, journal = {Hematology, transfusion and cell therapy}, volume = {46}, number = {4}, pages = {366-373}, pmid = {37442650}, issn = {2531-1387}, abstract = {INTRODUCTION: Acute leukemias (ALs) are aggressive diseases that lead to death without medical attention. We evaluated the association between delays in diagnosis and poor outcomes in AL by evaluating the symptom onset to treatment intervals in adults with newly diagnosed AL and their effect on an early death (ED).

METHODS: We assessed adults diagnosed with AL between 2015 and 2020 and evaluated baseline characteristics, the patient interval (PI), diagnostic interval (DI), treatment interval (TI) and the total time interval (TTI) to determine ED-associated factors.

MAIN RESULTS: We assessed 102 patients with acute lymphoblastic leukemia (ALL), 57 with acute myeloblastic leukemia (AML) and 29 with acute promyelocytic leukemia (APL). Median interval days were PI 14, DI 10, TI 4 and TTI 31.5. The TI and TTI intervals were lower in APL than in ALL and AML; TI 1 vs. 4 and 3 (p = 0.001) and TTI 21 vs. 31 and 35 (p = 0.016). The 30-day and 60-day EDs were 13.8% and 20.7%, mainly infections. ECOG > 2 (OR = 15.0) and PI < 7 days (OR = 4.06) were associated with 30-day ED; AML (OR = 2.69), high-risk (OR = 3.34), albumin < 3.5 g/dl (OR = 5) and platelets < 20 × 10[3]/uL (OR = 2.71) with a 60-day ED.

CONCLUSION: None of the interval-delays were associated with an ED. Intervals seemed to be longer in patients without an ED, except for the TI, probably because of "the waiting time paradox." Aggressive manifestations of disease may lead to shorter diagnostic intervals, but increased mortality.}, } @article {pmid37440197, year = {2023}, author = {Yang, J and Li, H and Zhao, Y}, title = {Dessert or Poison? The Roles of Glycosylation in Alzheimer's, Parkinson's, Huntington's Disease, and Amyotrophic Lateral Sclerosis.}, journal = {Chembiochem : a European journal of chemical biology}, volume = {24}, number = {16}, pages = {e202300017}, doi = {10.1002/cbic.202300017}, pmid = {37440197}, issn = {1439-7633}, mesh = {Humans ; Aged ; *Huntington Disease ; *Neurodegenerative Diseases ; *Alzheimer Disease ; *Amyotrophic Lateral Sclerosis ; *Parkinson Disease ; Glycosylation ; *Poisons ; Quality of Life ; }, abstract = {Ministry of Education and Key Laboratory of Neurons and glial cells of the central nervous system (CNS) are modified by glycosylation and rely on glycosylation to achieve normal neural function. Neurodegenerative disease is a common disease of the elderly, affecting their healthy life span and quality of life, and no effective treatment is currently available. Recent research implies that various glycosylation traits are altered during neurodegenerative diseases, suggesting a potential implication of glycosylation in disease pathology. Herein, we summarized the current knowledge about glycosylation associated with Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and Amyotrophic lateral sclerosis (ALS) pathogenesis, focusing on their promising functional avenues. Moreover, we collected research aimed at highlighting the need for such studies to provide a wealth of disease-related glycosylation information that will help us better understand the pathophysiological mechanisms and hopefully specific glycosylation information to provide further diagnostic and therapeutic directions for neurodegenerative diseases.}, } @article {pmid37439013, year = {2023}, author = {Zhou, Q and Kang, Q and Chen, W and Xu, R}, title = {Potential effects of brain lipid binding protein in the pathogenesis of amyotrophic lateral sclerosis.}, journal = {Science progress}, volume = {106}, number = {3}, pages = {368504231184320}, pmid = {37439013}, issn = {2047-7163}, mesh = {Animals ; Mice ; *Amyotrophic Lateral Sclerosis/genetics ; *Fatty Acid-Binding Protein 7/genetics ; *Neural Stem Cells ; Superoxide Dismutase-1 ; Disease Models, Animal ; }, abstract = {Current studies suggest that the abnormal alteration of brain lipid binding protein (BLBP) might participate in the pathogenesis of amyotrophic lateral sclerosis (ALS). However, the detailed understanding of ALS pathogenesis been yet to be elucidated. Therefore, this research intended to explore the potential effects of BLBP in ALS. The observation and analysis of BLBP-altered features in various anatomical areas and different spinal segments was conducted at the pre-onset, onset, and progression stages of Tg(SOD1*G93A)1Gur (TG) mice and the same periods of age-matched SOD1 wild-type (WT) mice by fluorescence immunohistochemistry and western blotting. BLBP-positive cells were comprehensively distributed in various spinal anatomical areas, especially in both the anterior and posterior horn, around the central canal and in anterior, lateral, and posterior funiculi. Overall, BLBP expression tended to increase from the pre-onset to the onset to the progression stages of the same periods of age-matched WT mice. Furthermore, in TG mice, BLBP expression in the entire spinal cord significantly increased from onset to the progression stage. BLBP was expressed in neurons, astrocytes, and radial glial cells, and at the early and late stages of neural precursor cells (NPCs) and was predominantly distributed outside the cell nucleus. The increase of BLBP-positive cells was closely related to neural cell reduction in TG mice. The distribution and increased expression of BLBP among the cervical, thoracic, and lumbar segments of the spinal cord might participate in the development of ALS and exert potential effects in the pathogenesis of ALS by regulating NPCs.}, } @article {pmid37438565, year = {2023}, author = {da Silveira Estevão, PL and Lemes, LFR and Soares, FLF and Nagata, N}, title = {Raman mapping for determination of TiO2 in different solid food samples by multivariate curve resolution with alternating least squares.}, journal = {Analytical and bioanalytical chemistry}, volume = {415}, number = {21}, pages = {5235-5245}, pmid = {37438565}, issn = {1618-2650}, support = {3080/20112011//Financiadora de Estudos e Projetos/ ; }, mesh = {Least-Squares Analysis ; *Titanium/analysis ; *Food ; Food Additives ; Multivariate Analysis ; }, abstract = {Titanium dioxide is a food additive commonly used as a white food coloring (E171). Its wide use by the food industry associated with the nanometric size distribution of the particles of this pigment has shown high genotoxicity associated with recurrent exposure by ingestion. Therefore, the use of E171 in food products has already been banned by some industries and in the European Union. Such banishment should soon be extended to other countries around the world, making it important to establish techniques for the efficient determination of TiO2 in different food products. The association between hyperspectral images and chemometric tools can be useful in this sense, aiming to enable the use of a single method for sample preparation and analysis of different types of food. Thus, the present work aims to evaluate the use of Raman mapping associated with the resolution of multivariate curves with alternating least squares (MCR-ALS) for the determination of titanium dioxide in solid food samples with different compositions, without the need to introduce specific sample preparation. The proposed method allowed for the first-time quantification of TiO2 in different food matrices without specific sample preparation, with a simple, rapid, accurate (93% of recovery), low detection limits (0.0111% m/m) and quantification (0.0370% m/m) and adequate linearity (r = 0.9990) and precise (standard deviation around 0.020-0.030% w/w) methodology. Such results highlight the potential use of Raman mapping associated with the MCR-ALS for quantification of the nano-TiO2 in commercial samples.}, } @article {pmid37438085, year = {2023}, author = {Balendra, R and Ruiz de Los Mozos, I and Odeh, HM and Glaria, I and Milioto, C and Wilson, KM and Ule, AM and Hallegger, M and Masino, L and Martin, S and Patani, R and Shorter, J and Ule, J and Isaacs, AM}, title = {Transcriptome-wide RNA binding analysis of C9orf72 poly(PR) dipeptides.}, journal = {Life science alliance}, volume = {6}, number = {9}, pages = {}, pmid = {37438085}, issn = {2575-1077}, support = {/WT_/Wellcome Trust/United Kingdom ; MR/S006591/1/MRC_/Medical Research Council/United Kingdom ; 107196/Z/14/Z/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Humans ; *Transcriptome/genetics ; C9orf72 Protein/genetics ; *Gene Expression Profiling ; Poly A ; Dipeptides ; RNA/genetics ; }, abstract = {An intronic GGGGCC repeat expansion in C9orf72 is a common genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia. The repeats are transcribed in both sense and antisense directions to generate distinct dipeptide repeat proteins, of which poly(GA), poly(GR), and poly(PR) have been implicated in contributing to neurodegeneration. Poly(PR) binding to RNA may contribute to toxicity, but analysis of poly(PR)-RNA binding on a transcriptome-wide scale has not yet been carried out. We therefore performed crosslinking and immunoprecipitation (CLIP) analysis in human cells to identify the RNA binding sites of poly(PR). We found that poly(PR) binds to nearly 600 RNAs, with the sequence GAAGA enriched at the binding sites. In vitro experiments showed that poly(GAAGA) RNA binds poly(PR) with higher affinity than control RNA and induces the phase separation of poly(PR) into condensates. These data indicate that poly(PR) preferentially binds to poly(GAAGA)-containing RNAs, which may have physiological consequences.}, } @article {pmid37437982, year = {2023}, author = {Sharma, K and Sarkar, J and Trisal, A and Ghosh, R and Dixit, A and Singh, AK}, title = {Targeting mitochondrial dysfunction to salvage cellular senescence for managing neurodegeneration.}, journal = {Advances in protein chemistry and structural biology}, volume = {136}, number = {}, pages = {309-337}, doi = {10.1016/bs.apcsb.2023.02.016}, pmid = {37437982}, issn = {1876-1631}, mesh = {Humans ; *Cellular Senescence ; Mitochondria ; *Alzheimer Disease ; Cyclin-Dependent Kinase Inhibitor Proteins ; }, abstract = {Aging is an inevitable phenomenon that causes a decline in bodily functions over time. One of the most important processes that play a role in aging is senescence. Senescence is characterized by accumulation of cells that are no longer functional but elude the apoptotic pathway. These cells secrete inflammatory molecules that comprise the senescence associated secretory phenotype (SASP). Several essential molecules such as p53, Rb, and p16INK4a regulate the senescence process. Mitochondrial regulation has been found to play an important role in senescence. Reactive oxygen species (ROS) generated from mitochondria can affect cellular senescence by inducing the persistent DNA damage response, thus stabilizing the senescence. Evidently, senescence plays a major contributory role to the development of age-related neurological disorders. In this chapter, we discuss the role of senescence in the progression and onset of several neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. Moreover, we also discuss the efficacy of certain molecules like MitoQ, SkQ1, and Latrepirdine that could be proven therapeutics with respect to these disorders by regulating mitochondrial activity.}, } @article {pmid37436778, year = {2023}, author = {Zamiri, K and Kesari, S and Paul, K and Hwang, SH and Hammock, B and Kaczor-Urbanowicz, KE and Urbanowicz, A and Gao, L and Whitelegge, J and Fiala, M}, title = {Therapy of autoimmune inflammation in sporadic amyotrophic lateral sclerosis: Dimethyl fumarate and H-151 downregulate inflammatory cytokines in the cGAS-STING pathway.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {37}, number = {8}, pages = {e23068}, pmid = {37436778}, issn = {1530-6860}, support = {R01 NS078410/NS/NINDS NIH HHS/United States ; R35 ES030443/ES/NIEHS NIH HHS/United States ; }, mesh = {Humans ; *Cytokines/metabolism ; Interleukin-17 ; Dimethyl Fumarate ; Leukocytes, Mononuclear/metabolism ; *Amyotrophic Lateral Sclerosis/drug therapy ; Granzymes ; Inflammation/drug therapy ; Nucleotidyltransferases ; }, abstract = {In sporadic amyotrophic lateral sclerosis (sALS), IL-17A- and granzyme-positive cytotoxic T lymphocytes (CTL), IL-17A-positive mast cells, and inflammatory macrophages invade the brain and spinal cord. In some patients, the disease starts following a trauma or a severe infection. We examined cytokines and cytokine regulators over the disease course and found that, since the early stages, peripheral blood mononuclear cells (PBMC) exhibit increased expression of inflammatory cytokines IL-12A, IFN-γ, and TNF-α, as well as granzymes and the transcription factors STAT3 and STAT4. In later stages, PBMCs upregulated the autoimmunity-associated cytokines IL-23A and IL-17B, and the chemokines CXCL9 and CXCL10, which attract CTL and monocytes into the central nervous system. The inflammation is fueled by the downregulation of IL-10, TGFβ, and the inhibitory T-cell co-receptors CTLA4, LAG3, and PD-1, and, in vitro, by stimulation with the ligand PD-L1. We investigated in two sALS patients the regulation of the macrophage transcriptome by dimethyl fumarate (DMF), a drug approved against multiple sclerosis and psoriasis, and the cyclic GMP-AMP synthase/stimulator of interferon genes (cGAS/STING) pathway inhibitor H-151. Both DMF and H-151 downregulated the expression of granzymes and the pro-inflammatory cytokines IL-1β, IL-6, IL-15, IL-23A, and IFN-γ, and induced a pro-resolution macrophage phenotype. The eicosanoid epoxyeicosatrienoic acids (EET) from arachidonic acid was anti-inflammatory in synergy with DMF. H-151 and DMF are thus candidate drugs targeting the inflammation and autoimmunity in sALS via modulation of the NFκB and cGAS/STING pathways.}, } @article {pmid37436254, year = {2023}, author = {Cunha-Correia, CD and Gama, MDP and Fontana, PN and Fantini, FGMM and Prado, GF and Dourado Júnior, MET and Schwingel, PA}, title = {Noninvasive mechanical ventilation assistance in amyotrophic lateral sclerosis: a systematic review.}, journal = {Sao Paulo medical journal = Revista paulista de medicina}, volume = {142}, number = {1}, pages = {e2022470}, pmid = {37436254}, issn = {1806-9460}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy/complications ; *Noninvasive Ventilation/methods ; Quality of Life ; Respiration, Artificial/adverse effects ; *Respiratory Insufficiency/therapy/complications ; }, abstract = {BACKGROUND: Respiratory failure is the most common cause of death in patients with amyotrophic lateral sclerosis (ALS), and morbidity is related to poor quality of life (QOL). Non-invasive ventilation (NIV) may be associated with prolonged survival and QOL in patients with ALS.

OBJECTIVES: To assess whether NIV is effective and safe for patients with ALS in terms of survival and QOL, alerting the health system.

DESIGN AND SETTING: Systematic review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting standards using population, intervention, comparison, and outcome strategies.

METHODS: The Cochrane Library, CENTRAL, MEDLINE, LILACS, EMBASE, and CRD databases were searched based on the eligibility criteria for all types of studies on NIV use in patients with ALS published up to January 2022. Data were extracted from the included studies, and the findings were presented using a narrative synthesis.

RESULTS: Of the 120 papers identified, only 14 were related to systematic reviews. After thorough reading, only one meta-analysis was considered eligible. In the second stage, 248 studies were included; however, only one systematic review was included. The results demonstrated that NIV provided relief from the symptoms of chronic hypoventilation, increased survival, and improved QOL compared to standard care. These results varied according to clinical phenotype.

CONCLUSIONS: NIV in patients with ALS improves the outcome and can delay the indication for tracheostomy, reducing expenditure on hospitalization and occupancy of intensive care unit beds.

PROSPERO database: CRD42021279910 - https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=279910.}, } @article {pmid37435576, year = {2023}, author = {Titus, MB and Chang, AW and Popitsch, N and Ebmeier, CC and Bono, JM and Olesnicky, EC}, title = {The identification of protein and RNA interactors of the splicing factor Caper in the adult Drosophila nervous system.}, journal = {Frontiers in molecular neuroscience}, volume = {16}, number = {}, pages = {1114857}, pmid = {37435576}, issn = {1662-5099}, support = {R15 NS104976/NS/NINDS NIH HHS/United States ; }, abstract = {Post-transcriptional gene regulation is a fundamental mechanism that helps regulate the development and healthy aging of the nervous system. Mutations that disrupt the function of RNA-binding proteins (RBPs), which regulate post-transcriptional gene regulation, have increasingly been implicated in neurological disorders including amyotrophic lateral sclerosis, Fragile X Syndrome, and spinal muscular atrophy. Interestingly, although the majority of RBPs are expressed widely within diverse tissue types, the nervous system is often particularly sensitive to their dysfunction. It is therefore critical to elucidate how aberrant RNA regulation that results from the dysfunction of ubiquitously expressed RBPs leads to tissue specific pathologies that underlie neurological diseases. The highly conserved RBP and alternative splicing factor Caper is widely expressed throughout development and is required for the development of Drosophila sensory and motor neurons. Furthermore, caper dysfunction results in larval and adult locomotor deficits. Nonetheless, little is known about which proteins interact with Caper, and which RNAs are regulated by Caper. Here we identify proteins that interact with Caper in both neural and muscle tissue, along with neural specific Caper target RNAs. Furthermore, we show that a subset of these Caper-interacting proteins and RNAs genetically interact with caper to regulate Drosophila gravitaxis behavior.}, } @article {pmid37434215, year = {2023}, author = {Riemenschneider, H and Simonetti, F and Sheth, U and Katona, E and Roth, S and Hutten, S and Farny, D and Michaelsen, M and Nuscher, B and Schmidt, MK and Flatley, A and Schepers, A and Gruijs da Silva, LA and Zhou, Q and Klopstock, T and Liesz, A and Arzberger, T and Herms, J and Feederle, R and Gendron, TF and Dormann, D and Edbauer, D}, title = {Targeting the glycine-rich domain of TDP-43 with antibodies prevents its aggregation in vitro and reduces neurofilament levels in vivo.}, journal = {Acta neuropathologica communications}, volume = {11}, number = {1}, pages = {112}, pmid = {37434215}, issn = {2051-5960}, mesh = {Animals ; Mice ; *Antibodies, Monoclonal ; Epitopes ; Immunization ; *Intermediate Filaments ; NF-kappa B ; }, abstract = {Cytoplasmic aggregation and concomitant nuclear clearance of the RNA-binding protein TDP-43 are found in ~ 90% of cases of amyotrophic lateral sclerosis and ~ 45% of patients living with frontotemporal lobar degeneration, but no disease-modifying therapy is available. Antibody therapy targeting other aggregating proteins associated with neurodegenerative disorders has shown beneficial effects in animal models and clinical trials. The most effective epitopes for safe antibody therapy targeting TDP-43 are unknown. Here, we identified safe and effective epitopes in TDP-43 for active and potential future passive immunotherapy. We prescreened 15 peptide antigens covering all regions of TDP-43 to identify the most immunogenic epitopes and to raise novel monoclonal antibodies in wild-type mice. Most peptides induced a considerable antibody response and no antigen triggered obvious side effects. Thus, we immunized mice with rapidly progressing TDP-43 proteinopathy ("rNLS8" model) with the nine most immunogenic peptides in five pools prior to TDP-43ΔNLS transgene induction. Strikingly, combined administration of two N-terminal peptides induced genetic background-specific sudden lethality in several mice and was therefore discontinued. Despite a strong antibody response, no TDP-43 peptide prevented the rapid body weight loss or reduced phospho-TDP-43 levels as well as the profound astrogliosis and microgliosis in rNLS8 mice. However, immunization with a C-terminal peptide containing the disease-associated phospho-serines 409/410 significantly lowered serum neurofilament light chain levels, indicative of reduced neuroaxonal damage. Transcriptomic profiling showed a pronounced neuroinflammatory signature (IL-1β, TNF-α, NfκB) in rNLS8 mice and suggested modest benefits of immunization targeting the glycine-rich region. Several novel monoclonal antibodies targeting the glycine-rich domain potently reduced phase separation and aggregation of TDP-43 in vitro and prevented cellular uptake of preformed aggregates. Our unbiased screen suggests that targeting the RRM2 domain and the C-terminal region of TDP-43 by active or passive immunization may be beneficial in TDP-43 proteinopathies by inhibiting cardinal processes of disease progression.}, } @article {pmid37433768, year = {2023}, author = {Zhang, W and Xiao, D and Mao, Q and Xia, H}, title = {Role of neuroinflammation in neurodegeneration development.}, journal = {Signal transduction and targeted therapy}, volume = {8}, number = {1}, pages = {267}, pmid = {37433768}, issn = {2059-3635}, support = {UL1 TR002538/TR/NCATS NIH HHS/United States ; }, mesh = {Animals ; *Alzheimer Disease/genetics ; *Amyotrophic Lateral Sclerosis/genetics ; Inflammation/genetics ; Neuroinflammatory Diseases ; *Parkinson Disease/genetics ; Protein Aggregates ; Humans ; Clinical Trials as Topic ; Disease Models, Animal ; }, abstract = {Studies in neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease and Amyotrophic lateral sclerosis, Huntington's disease, and so on, have suggested that inflammation is not only a result of neurodegeneration but also a crucial player in this process. Protein aggregates which are very common pathological phenomenon in neurodegeneration can induce neuroinflammation which further aggravates protein aggregation and neurodegeneration. Actually, inflammation even happens earlier than protein aggregation. Neuroinflammation induced by genetic variations in CNS cells or by peripheral immune cells may induce protein deposition in some susceptible population. Numerous signaling pathways and a range of CNS cells have been suggested to be involved in the pathogenesis of neurodegeneration, although they are still far from being completely understood. Due to the limited success of traditional treatment methods, blocking or enhancing inflammatory signaling pathways involved in neurodegeneration are considered to be promising strategies for the therapy of neurodegenerative diseases, and many of them have got exciting results in animal models or clinical trials. Some of them, although very few, have been approved by FDA for clinical usage. Here we comprehensively review the factors affecting neuroinflammation and the major inflammatory signaling pathways involved in the pathogenicity of neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, and Amyotrophic lateral sclerosis. We also summarize the current strategies, both in animal models and in the clinic, for the treatment of neurodegenerative diseases.}, } @article {pmid37433222, year = {2023}, author = {Shihora, A and Elias, RD and Hammond, JA and Ghirlando, R and Deshmukh, L}, title = {ALS Variants of Annexin A11's Proline-Rich Domain Impair Its S100A6-Mediated Fibril Dissolution.}, journal = {ACS chemical neuroscience}, volume = {14}, number = {15}, pages = {2583-2589}, pmid = {37433222}, issn = {1948-7193}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/metabolism ; Annexins/genetics ; *Neurodegenerative Diseases ; Solubility ; Amyloid/metabolism ; Proline/genetics ; S100 Calcium Binding Protein A6 ; Cell Cycle Proteins/chemistry/metabolism ; }, abstract = {Mutations in the proline-rich domain (PRD) of annexin A11 are linked to amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease, and generate abundant neuronal A11 inclusions by an unknown mechanism. Here, we demonstrate that recombinant A11-PRD and its ALS-associated variants form liquidlike condensates that transform into β-sheet-rich amyloid fibrils. Surprisingly, these fibrils dissolved in the presence of S100A6, an A11 binding partner overexpressed in ALS. The ALS variants of A11-PRD showed longer fibrillization half-times and slower dissolution, even though their binding affinities for S100A6 were not significantly affected. These findings indicate a slower fibril-to-monomer exchange for these ALS variants, resulting in a decreased level of S100A6-mediated fibril dissolution. These ALS-A11 variants are thus more likely to remain aggregated despite their slower fibrillization.}, } @article {pmid37433093, year = {2023}, author = {Wong, W}, title = {Managed care considerations to improve health care utilization for patients with ALS.}, journal = {The American journal of managed care}, volume = {29}, number = {7 Suppl}, pages = {S120-S126}, doi = {10.37765/ajmc.2023.89388}, pmid = {37433093}, issn = {1936-2692}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy ; Edaravone ; Activities of Daily Living ; Quality of Life ; Patient Acceptance of Health Care ; Managed Care Programs ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatally progressive degenerative disease, with many patients succumbing to the condition within 3 to 5 years after diagnosis. It is a rare, orphan disease with an estimated US prevalence of 25,000 patients. Patients with ALS and their caregivers are faced with a substantial financial burden as a result of the condition, as ALS has an estimated national financial burden of $1.03 billion. A significant driver of the patient financial burden includes the continued need for caregiver support as the weakening of muscles progresses to dysphagia and dyspnea, making it difficult to complete activities of daily living as the disease progresses. Caregivers also experience financial burdens, as well as feelings of anxiety, depression, and decreased quality of life. In addition to needed caregiver support, patients with ALS and their families also incur substantial nonmedical costs including travel expenses, home modifications such as ramps, and indirect costs such as productivity loss. Due to the wide range of clinical symptoms that patients may exhibit when first presenting with ALS symptoms, diagnosis is often delayed, which negatively affects patient outcomes and impacts missed opportunity for clinical trial recruitment aimed at developing new disease-modifying therapies. Additionally, delay in diagnosis and referral to ALS treatment centers results in increased overall health care costs. Telemedicine may be a tool used to promote timely care from an ALS treatment center in addition to clinical trial participation for those patients who cannot overcome mobility barriers for care. Currently, 4 therapies are approved for the treatment of ALS. Riluzole has demonstrated modest improvement in survival. Other recently approved therapies include oral edaravone, a combination therapy of sodium phenylbutyrate and taurursodiol (PB/TURSO), and tofersen, which is administered intrathecally and approved under an accelerated approval. Long-term studies have shown PB/TURSO to have a dual benefit on survival and function. The Institute for Clinical and Economic Review (ICER) 2022 Evidence Report for ALS does not value the high price points of edaravone and PB/TURSO as cost-effective based on the current evidence, despite valuing the need for new treatment options for this patient population.}, } @article {pmid37433092, year = {2023}, author = {Lynch, K}, title = {Optimizing pharmacologic treatment for ALS to improve outcomes and quality of life.}, journal = {The American journal of managed care}, volume = {29}, number = {7 Suppl}, pages = {S112-S119}, doi = {10.37765/ajmc.2023.89389}, pmid = {37433092}, issn = {1936-2692}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy ; Quality of Life ; Riluzole ; Edaravone ; }, abstract = {Just 3 disease-modifying treatments-edaravone, riluzole, and sodium phenylbutyrate and taurursodiol (PB/TURSO)-are currently FDA approved to slow progression of amyotrophic lateral sclerosis (ALS). A fourth therapy has been recently approved under accelerated approval and is contingent upon verification of clinical benefit in confirmatory trials(s). Therapy selection is based largely upon patient characteristics, as guidelines have not been updated since the recent approval of PB/TURSO or accelerated approval of tofersen. Managing ALS symptomatically is important to improve patients' quality of life. Although evidence is lacking for many pharmacologic therapies, providers use symptomatic treatments to address common symptoms including anxiety, depression, emotional lability (pseudobulbar affect), fasciculations, fatigue, insomnia, muscle cramps or spasms, musculoskeletal pain due to immobility, neuropathic type pain, excessive salivation (sialorrhea), spasticity, constipation, and urinary urgency. Emerging agents offer some hope for patients with ALS. Among the drugs, biologics, and interventions under investigation for ALS are an oral tyrosine kinase inhibitor, RIPK1 inhibition, the use of mesenchymal stem cells, antisense oligonucleotides, sequential administration of all experimental treatments in a new study design, and modification of the patient's own mesenchymal stem cells.}, } @article {pmid37433091, year = {2023}, author = {Lynch, K}, title = {Pathogenesis and presentation of ALS: examining reasons for delayed diagnosis and identifying opportunities for improvement.}, journal = {The American journal of managed care}, volume = {29}, number = {7 Suppl}, pages = {S104-S111}, doi = {10.37765/ajmc.2023.89390}, pmid = {37433091}, issn = {1936-2692}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis ; Delayed Diagnosis ; Quality of Life ; Brain ; Risk Factors ; }, abstract = {Amyotrophic lateral sclerosis (ALS), or Lou Gehrig disease, is a progressive, always-fatal neuromuscular disease characterized by motor neuron degeneration in the brain and spinal cord. As upper and lower motor neurons fail, inability to transmit messages to the muscles causes muscle stiffness, atrophy, and wasting. The incidence of this incurable disease is increasing in the United States, and its prognosis is grim. On average, patients survive about 3 to 5 years from symptom onset. Until recently, few risk factors were known, but some are newly emerging. About 10% of cases are related to genetic variants. Patients who develop ALS often experience diagnostic delays (10-16 months on average), and its heterogeneity contributes to that delay. Diagnosis is based primarily on clinical signs and symptoms and exclusion of other causes of motor neuron dysfunction. Reliable, accessible biomarkers are needed to aid early ALS diagnosis, differentiate from ALS-mimicking diseases, predict survival, and monitor disease progression and treatment response. Misdiagnosing ALS can have devastating consequences, including unnecessary emotional burden, delayed and/or inappropriate treatment, and undue financial burden. The grim prognosis and sure progression to death creates considerable burden and reduces quality of life for patients and caregivers.}, } @article {pmid37432640, year = {2024}, author = {Maurya, S and Gaur, M and Yadav, AB}, title = {Staphylococcus aureus Biofilm Destabilization by Tween-80 and Lung Surfactants to Overcome Biofilm-Imposed Drug Resistance.}, journal = {Applied biochemistry and biotechnology}, volume = {196}, number = {3}, pages = {1558-1569}, pmid = {37432640}, issn = {1559-0291}, mesh = {Animals ; *Staphylococcus aureus ; Anti-Bacterial Agents/pharmacology ; Polysorbates/pharmacology ; Biofilms ; *Staphylococcal Infections/microbiology ; Surface-Active Agents/pharmacology ; Drug Resistance ; Lung ; }, abstract = {This study is aimed to evaluating the potential of tween-80 and artificial lung surfactant (ALS) to destabilize S. aureus biofilm. The biofilm destabilization was studied by crystal violet staining, bright field microscopy, and scanning electron microscopy (SEM). During the study, S. aureus biofilm was exposed with tween-80 along various concentrations (1%, 0.1%, and 0.05%) or LS (lung surfactant) at (2.5%, 5%, and 15%) for 2 hrs. It was observed that 0.1% of tween-80 destabilized 63.83 ± 4.35% and 15% ALS 77 ± 1.7% biofilm in comparison to without treatment. The combination of tween-80 and ALS was used and showed a synergistic effect to destabilize 83.4 ± 1.46% biofilm. These results showed the potential of tween-80 and ALS as biofilm disruptors, which further needs to explore in an in-vivo animal model to access the actual potential of biofilm disruption in natural conditions. This study could play a pivotal role to overcome the problem of antibiotic resistance imposed due to biofilm formation to combat antibiotic resistance imposed by bacteria.}, } @article {pmid37432384, year = {2023}, author = {Renke, G and Almeida, VBP and Souza, EA and Lessa, S and Teixeira, RL and Rocha, L and Sousa, PL and Starling-Soares, B}, title = {Clinical Outcomes of the Deleterious Effects of Aluminum on Neuro-Cognition, Inflammation, and Health: A Review.}, journal = {Nutrients}, volume = {15}, number = {9}, pages = {}, pmid = {37432384}, issn = {2072-6643}, mesh = {Humans ; *Aluminum/toxicity ; *Inflammation ; Adjuvants, Immunologic ; Chelating Agents ; Cognition ; Food Additives ; }, abstract = {Introduction: In the scenario of metal toxicity, aluminum (Al) stands out as a ubiquitous type of metal that can be combined with other elements and form different compounds. Al is widely used daily as an adjuvant in vaccines, antacids, food additives (as components of AI-containing food additives), skin care products, cosmetics, and kitchenware, and can be an element or contaminant present in our daily life. Objective: To present a review of the main deleterious effects of Al on human health. Methods: The search was carried out from September 2022 to February 2023 in the Scopus, PubMed, Science Direct, Scielo, and Google Scholar databases, using scientific articles from 2012 to 2023. The quality of the studies was based on the GRADE instrument, and the risk of bias was analyzed according to the Cochrane instrument. Results and Conclusions: A total of 115 files were search returned. Further, 95 articles were evaluated, and 44 were included in this review. Based on the results, measuring Al's relevance to health is essential in medicine. Several studies have demonstrated clinical outcomes and metabolic alterations with Al exposure. The tolerable weekly intake established by the European Food Safety Authority (EFSA) of 1 mg Al/kg body weight can be achieved through dietary exposure alone. Proven neurotoxicity in humans is the critical adverse effect of Al. A carcinogenic effect of Al has not been proven so far. Preventive medicine advocates that exposure to Al should be kept as low as possible. Chelating agents, such as calcium disodium ethylene diamine tetraacetic acid and deferoxamine, are options for acute poisoning, and monomethysilanetriol supplementation may be a long-term strategy with chelation potential. Further studies are needed to assess the impacts of Al on human health.}, } @article {pmid37431963, year = {2023}, author = {Pérez-Berlanga, M and Wiersma, VI and Zbinden, A and De Vos, L and Wagner, U and Foglieni, C and Mallona, I and Betz, KM and Cléry, A and Weber, J and Guo, Z and Rigort, R and de Rossi, P and Manglunia, R and Tantardini, E and Sahadevan, S and Stach, O and Hruska-Plochan, M and Allain, FH and Paganetti, P and Polymenidou, M}, title = {Loss of TDP-43 oligomerization or RNA binding elicits distinct aggregation patterns.}, journal = {The EMBO journal}, volume = {42}, number = {17}, pages = {e111719}, pmid = {37431963}, issn = {1460-2075}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism ; *Frontotemporal Lobar Degeneration/metabolism ; DNA-Binding Proteins/metabolism ; Neurons/metabolism ; RNA/genetics ; }, abstract = {Aggregation of the RNA-binding protein TAR DNA-binding protein 43 (TDP-43) is the key neuropathological feature of neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). In physiological conditions, TDP-43 is predominantly nuclear, forms oligomers, and is contained in biomolecular condensates assembled by liquid-liquid phase separation (LLPS). In disease, TDP-43 forms cytoplasmic or intranuclear inclusions. How TDP-43 transitions from physiological to pathological states remains poorly understood. Using a variety of cellular systems to express structure-based TDP-43 variants, including human neurons and cell lines with near-physiological expression levels, we show that oligomerization and RNA binding govern TDP-43 stability, splicing functionality, LLPS, and subcellular localization. Importantly, our data reveal that TDP-43 oligomerization is modulated by RNA binding. By mimicking the impaired proteasomal activity observed in ALS/FTLD patients, we found that monomeric TDP-43 forms inclusions in the cytoplasm, whereas its RNA binding-deficient counterpart aggregated in the nucleus. These differentially localized aggregates emerged via distinct pathways: LLPS-driven aggregation in the nucleus and aggresome-dependent inclusion formation in the cytoplasm. Therefore, our work unravels the origins of heterogeneous pathological species reminiscent of those occurring in TDP-43 proteinopathy patients.}, } @article {pmid37431079, year = {2023}, author = {Kurashige, T}, title = {[Histopathological Diagnostic Marker for ALS: Phosphorylated Transacting Response DNA-Binding Protein of 43kDa in Intramuscular Nerve Bundles].}, journal = {Brain and nerve = Shinkei kenkyu no shinpo}, volume = {75}, number = {7}, pages = {877-887}, doi = {10.11477/mf.1416202436}, pmid = {37431079}, issn = {1881-6096}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis ; Retrospective Studies ; Autopsy ; DNA-Binding Proteins ; }, abstract = {The discovery of transacting response DNA-binding protein of 43 kDa (TDP-43) led to a deeper understanding of the pathogenesis of amyotrophic lateral sclerosis (ALS). Since this discovery, blood and cerebrospinal fluid biomarkers of ALS have been reported. However, these biomarkers do not exhibit sufficient specificity for ALS. Our case-control postmortem and retrospective muscle biopsy cohort studies revealed phosphorylated TDP-43 in intramuscular nerve bundles, which precedes the clinical fulfillment of the Gold Coast criteria. We attempted to establish a histopathological biomarker for ALS and identify molecular targets for the treatment of lower motor dysfunction in patients with ALS.}, } @article {pmid37430314, year = {2023}, author = {Mitsumoto, H and Cheung, K and Oskarsson, B and Andrews, HF and Jang, GE and Andrews, JA and Shah, JS and Fernandes, JA and McElhiney, M and Santella, RM}, title = {Randomized double-blind personalized N-of-1 clinical trial to test the safety and potential efficacy of TJ-68 for treating muscle cramps in amyotrophic lateral sclerosis (ALS): study protocol for a TJ-68 trial.}, journal = {Trials}, volume = {24}, number = {1}, pages = {449}, pmid = {37430314}, issn = {1745-6215}, support = {no number//Tsumura and Company/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/complications/diagnosis/drug therapy ; Drug Combinations ; *Drugs, Chinese Herbal ; Muscle Cramp/diagnosis/drug therapy/etiology ; Quality of Life ; Randomized Controlled Trials as Topic ; }, abstract = {INTRODUCTION/AIMS: Muscle cramps are a common and often disabling symptom in amyotrophic lateral sclerosis (ALS), a devastating and incurable neurodegenerative disorder. To date, there are no medications specifically approved for the treatment of muscle cramps. Ameliorating muscle cramps in ALS may improve and sustain quality of life. A widely prescribed traditional Japanese (Kampo) medicine against muscle cramps, shakuyakukanzoto (TJ-68), has been studied in advanced liver disease, spinal stenosis, kidney failure, and diabetic neuropathy. The Japanese ALS Management Guideline mentions TJ-68 for difficult muscle cramps in ALS. Therefore, the rationale of our trial is to investigate the safety and effectiveness of TJ-68 in treating painful and disabling muscle cramps in people with ALS outside of Japan. Accordingly, we are conducting a randomized clinical trial to test the safety and efficacy of TJ-68 in participants with ALS reporting frequent muscle cramps using an innovative, personalized N-of-1 design. If successful, TJ-68 may be used for muscle cramps in a broader population of people with ALS.

METHODS: This is a two-site, double-blind, randomized personalized N-of-1 early clinical trial with TJ-68. At least 22 participants with ALS and daily muscle cramps will receive drug or placebo for 2 weeks (one treatment period) followed by a 1-week washout in a four-period cross-over design. While the primary objective is to evaluate the safety of TJ-68, the study has 85% power to detect a one-point shift on the Visual Analog Scale for Muscle Cramps Affecting Overall Daily Activity of the Columbia Muscle Cramp Scale (MCS). Secondary outcomes include the full MCS score, a Cramp Diary, Clinical Global Impression of Changes, Goal Attainment Scale, quality of life scale and ALS functional rating scale-revised (ALSFRS-R).

DISCUSSION: The study is underway. A personalized N-of-1 trial design is an efficient approach to testing medications that alleviate muscle cramps in rare disorders. If TJ-68 proves safe and efficacious then it may be used to treat cramps in ALS, and help to improve and sustain quality of life.

TRIAL REGISTRATION: This clinical trial has been registered with ClinicalTrials.gov (NCT04998305), 8/9/2021.}, } @article {pmid37430221, year = {2023}, author = {Miyake, N and Igarashi, Y and Nakae, R and Mizobuchi, T and Masuno, T and Yokobori, S}, title = {Ventilator management and risk of air leak syndrome in patients with SARS-CoV-2 pneumonia: a single-center, retrospective, observational study.}, journal = {BMC pulmonary medicine}, volume = {23}, number = {1}, pages = {251}, pmid = {37430221}, issn = {1471-2466}, mesh = {Adult ; Humans ; SARS-CoV-2 ; Retrospective Studies ; *COVID-19/therapy ; *Pneumonia ; Ventilators, Mechanical ; Syndrome ; }, abstract = {BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia is reportedly associated with air leak syndrome (ALS), including mediastinal emphysema and pneumothorax, and has a high mortality rate. In this study, we compared values obtained every minute from ventilators to clarify the relationship between ventilator management and risk of developing ALS.

METHODS: This single-center, retrospective, observational study was conducted at a tertiary care hospital in Tokyo, Japan, over a 21-month period. Information on patient background, ventilator data, and outcomes was collected from adult patients with SARS-CoV-2 pneumonia on ventilator management. Patients who developed ALS within 30 days of ventilator management initiation (ALS group) were compared with those who did not (non-ALS group).

RESULTS: Of the 105 patients, 14 (13%) developed ALS. The median positive-end expiratory pressure (PEEP) difference was 0.20 cmH2O (95% confidence interval [CI], 0.20-0.20) and it was higher in the ALS group than in the non-ALS group (9.6 [7.8-20.2] vs. 9.3 [7.3-10.2], respectively). For peak pressure, the median difference was -0.30 cmH2O (95% CI, -0.30 - -0.20) (20.4 [17.0-24.4] in the ALS group vs. 20.9 [16.7-24.6] in the non-ALS group). The mean pressure difference of 0.0 cmH2O (95% CI, 0.0-0.0) (12.7 [10.9-14.6] vs. 13.0 [10.3-15.0], respectively) was also higher in the non-ALS group than in the ALS group. The difference in single ventilation volume per ideal body weight was 0.71 mL/kg (95% CI, 0.70-0.72) (8.17 [6.79-9.54] vs. 7.43 [6.03-8.81], respectively), and the difference in dynamic lung compliance was 8.27 mL/cmH2O (95% CI, 12.76-21.95) (43.8 [28.2-68.8] vs. 35.7 [26.5-41.5], respectively); both were higher in the ALS group than in the non-ALS group.

CONCLUSIONS: There was no association between higher ventilator pressures and the development of ALS. The ALS group had higher dynamic lung compliance and tidal volumes than the non-ALS group, which may indicate a pulmonary contribution to ALS. Ventilator management that limits tidal volume may prevent ALS development.}, } @article {pmid37429415, year = {2023}, author = {Asveda, T and Talwar, P and Ravanan, P}, title = {Exploring microglia and their phenomenal concatenation of stress responses in neurodegenerative disorders.}, journal = {Life sciences}, volume = {328}, number = {}, pages = {121920}, doi = {10.1016/j.lfs.2023.121920}, pmid = {37429415}, issn = {1879-0631}, mesh = {Humans ; Microglia/metabolism ; *Neurodegenerative Diseases/metabolism ; Central Nervous System/metabolism ; *Alzheimer Disease/metabolism ; *Parkinson Disease/metabolism ; }, abstract = {Neuronal cells are highly functioning but also extremely stress-sensitive cells. By defending the neuronal cells against pathogenic insults, microglial cells, a unique cell type, act as the frontline cavalry in the central nervous system (CNS). Their remarkable and unique ability to self-renew independently after their creation is crucial for maintaining normal brain function and neuroprotection. They have a wide range of molecular sensors that help maintain CNS homeostasis during development and adulthood. Despite being the protector of the CNS, studies have revealed that persistent microglial activation may be the root cause of innumerable neurodegenerative illnesses, including Alzheimer's disease (AD), Parkinson's disease (PD), and Amyotrophic Lateral Sclerosis (ALS). From our vigorous review, we state that there is a possible interlinking between pathways of Endoplasmic reticulum (ER) stress response, inflammation, and oxidative stress resulting in dysregulation of the microglial population, directly influencing the accumulation of pro-inflammatory cytokines, complement factors, free radicals, and nitric oxides leading to cell death via apoptosis. Recent research uses the suppression of these three pathways as a therapeutic approach to prevent neuronal death. Hence, in this review, we have spotlighted the advancement in microglial studies, which focus on their molecular defenses against multiple stresses, and current therapeutic strategies indirectly targeting glial cells for neurodevelopmental diseases.}, } @article {pmid37427714, year = {2023}, author = {Van Unnik, JWJ and Bakers, JNE and Kokx, S and Van Den Berg, LH and Visser-Meily, JMA and Beelen, A and Van Eijk, RPA}, title = {Portable fixed dynamometry enables home-based, reliable assessment of muscle strength in patients with amyotrophic lateral sclerosis: a pilot study.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {}, number = {}, pages = {1-10}, doi = {10.1080/21678421.2023.2231494}, pmid = {37427714}, issn = {2167-9223}, abstract = {OBJECTIVE: To determine the feasibility, reliability, and sensitivity of remotely monitoring muscle strength loss of knee extensors using a novel portable fixed dynamometer (PFD) in patients with amyotrophic lateral sclerosis (ALS).

METHODS: We conducted a pilot study with a newly developed device to measure knee extension strength. Patients performed unsupervised PFD measurements, biweekly, for 6 months at home. We evaluated feasibility using adherence and a device-specific questionnaire. Reliability was assessed by (1) comparing unsupervised and supervised measurements to identify systematic bias, and (2) comparing consecutive unsupervised measurements to determine test-retest reliability expressed as intraclass correlation coefficient (ICC) and standard error of measurement (SEM). Sensitivity to detect longitudinal change was described using linear mixed-effects models.

RESULTS: We enrolled 18 patients with ALS. Adherence was 86%, where all patients found that the device suitable to measure muscle strength at home; 4 patients (24%) found the measurements burdensome. The correlation between (un)supervised measurements was excellent (Pearson's r 0.97, 95%CI; 0.94 - 0.99) and no systematic bias was present (mean difference 0.13, 95%CI; -2.22 - 2.48, p = 0.91). Unsupervised measurements had excellent test-retest reliability with an average ICC of 0.97 (95%CI: 0.94 - 0.99) and SEM of 5.8% (95%CI: 4.8 - 7.0). Muscle strength declined monthly by 1.9 %predicted points (95%CI; -3.0 to -0.9, p = 0.001).

CONCLUSIONS: Using the PFD, it proved feasible to perform knee extension strength measurements at home which were reliable and sensitive for detecting muscle strength loss. Larger studies are warranted to compare the device with conventional outcomes.}, } @article {pmid37427570, year = {2023}, author = {Diaz Villanueva, L and Lada Colunga, B and Villanueva Ordóñez, MJ and Cuartas Álvarez, T and Cernuda Martinez, JA and Castro Delgado, R}, title = {Impact of the COVID-19 Pandemic on the Profile of Patients in SAMU-Asturias EMS (Spain): A Two-Year Retrospective Analysis of Advanced Life Support Unit Data.}, journal = {Prehospital and disaster medicine}, volume = {38}, number = {4}, pages = {430-435}, doi = {10.1017/S1049023X23006015}, pmid = {37427570}, issn = {1945-1938}, mesh = {Humans ; *COVID-19/epidemiology/prevention & control ; Cross-Sectional Studies ; *Emergency Medical Services/methods/statistics & numerical data ; Pandemics/prevention & control ; Retrospective Studies ; Spain/epidemiology ; *Advanced Cardiac Life Support/statistics & numerical data ; }, abstract = {INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic had important consequences on the health system. Emergency Medical Services (EMS) were a key element in the response and were forced to modify their daily procedures. The main objective of this study was to find out if there were differences in response times and in the profile of patients treated by the Advanced Life Support (ALS) units of Servicio de Asistencia Médica Urgente (SAMU)-Asturias, the EMS of the Principality of Asturias, between the pre-pandemic period and the pandemic period.

METHODOLOGY: This was a descriptive, cross-sectional, observational, and retrospective study that included all patients treated by SAMU-Asturias ALS from January 1, 2019 through December 31, 2020.

RESULTS: The pandemic has had an impact on daily activity of SAMU-Asturias, with a 9.2% decrease in daily ALS services during the pandemic, longer prehospital times during the pandemic period (mean = 54'35"; SD = 0'48"; P = 0.00) mainly due to an increase in scene time (mean = 28'01"; SD = 12'57"; P = 0.00), and a slight increase in the average age of patients during the pandemic in relation to the pre-pandemic period. No differences were found between the types of incidents for ALS or between the resolution of the patients.

CONCLUSIONS: The COVID-19 pandemic mainly affects prehospital times in an emergency service, with no differences being observed in types of incidents; in EMS future pandemic planning, this should be taken into consideration.}, } @article {pmid37427325, year = {2023}, author = {Najafi, S and Najafi, P and Kaffash Farkhad, N and Hosseini Torshizi, G and Assaran Darban, R and Boroumand, AR and Sahab-Negah, S and Khodadoust, MA and Tavakol-Afshari, J}, title = {Mesenchymal stem cell therapy in amyotrophic lateral sclerosis (ALS) patients: A comprehensive review of disease information and future perspectives.}, journal = {Iranian journal of basic medical sciences}, volume = {26}, number = {8}, pages = {872-881}, pmid = {37427325}, issn = {2008-3866}, abstract = {Amyotrophic lateral sclerosis (ALS) is a rare deadly progressive neurological disease that primarily affects the upper and lower motor neurons with an annual incidence rate of 0.6 to 3.8 per 100,000 people. Weakening and gradual atrophy of the voluntary muscles are the first signs of the disease onset affecting all aspects of patients' lives, including eating, speaking, moving, and even breathing. Only 5-10% of patients have a familial type of the disease and show an autosomal dominant pattern, but the cause of the disease is unknown in the remaining 90% of patients (Sporadic ALS). However, in both types of disease, the patient's survival is 2 to 5 years from the disease onset. Some clinical and molecular biomarkers, magnetic resonance imaging (MRI), blood or urine test, muscle biopsy, and genetic testing are complementary methods for disease diagnosis. Unfortunately, with the exception of Riluzole, the only medically approved drug for the management of this disease, there is still no definitive cure for it. In this regard, the use of mesenchymal stem cells (MSCs) for the treatment or management of the disease has been common in preclinical and clinical studies for many years. MSCs are multipotent cells having immunoregulatory, anti-inflammatory, and differentiation ability that makes them a good candidate for this purpose. This review article aims to discuss multiple aspects of ALS disease and focus on MSCs' role in disease management based on performed clinical trials.}, } @article {pmid37427180, year = {2023}, author = {Chapagain, S and Khati, N and Lama, R and Karki, R and Aryal, R and Pangyani, B and Koirala, A}, title = {Amyotrophic lateral sclerosis with respiratory failure and dysautonomia: a case report.}, journal = {Annals of medicine and surgery (2012)}, volume = {85}, number = {7}, pages = {3623-3625}, pmid = {37427180}, issn = {2049-0801}, abstract = {UNLABELLED: Amyotrophic lateral sclerosis (ALS) is a disease that affects both upper and lower motor neurons, causing a range of symptoms beyond the motor system. Recent research has shown that the autonomic nervous system can also be affected, with symptoms such as orthostatic hypotension, fluctuations in blood pressure, and dizziness being reported.

CASE PRESENTATION: A 58-year-old male presented with left lower limb limping, difficulty climbing stairs, and left foot weakness, followed by right upper limb weakness and was diagnosed with ALS and received edaravone and riluzole treatment. He presented again with right lower limb weakness, shortness of breath, and wide fluctuations in blood pressure, leading to ICU admission with new diagnosis of ALS with dysautonomia with respiratory failure and was managed with non-invasive ventilation, physiotherapy, and gait training exercises.

CLINICAL DISCUSSION: ALS is a progressive neurodegenerative disease affecting motor neurons but non-motor symptoms can also occur, including dysautonomia, which can result in blood pressure fluctuations. Dysautonomia in ALS is caused by several mechanisms such as severe muscle atrophy, prolonged ventilatory support, and upper and lower motor neuron lesions. Management of ALS involves giving a definitive diagnosis, providing nutritional support, using disease-modifying drugs such as riluzole and non-invasive ventilation to improve survival and quality of life. Early diagnosis is essential for effective management of the disease.

CONCLUSION: Early diagnosis, use of disease-modifying drugs, non-invasive ventilation, and maintaining the patient's nutritional status are crucial for managing ALS which can have non-motor symptoms as well.}, } @article {pmid37427010, year = {2023}, author = {Mballa Yene, BV and Lee, SY and Park, KS and Kang, YJ and Seo, SH and Yoo, JI}, title = {Prevalence of Sarcopenia in Africa: A Systematic Review.}, journal = {Clinical interventions in aging}, volume = {18}, number = {}, pages = {1021-1035}, pmid = {37427010}, issn = {1178-1998}, mesh = {Male ; Female ; Humans ; *Sarcopenia/epidemiology/diagnosis ; Prevalence ; Africa/epidemiology ; }, abstract = {OBJECTIVE: The world population gradually getting older, age-related sarcopenia is becoming more frequent. Known to be highly prevalent in high income countries, relative data in Africa are still scarce. This review aims to estimate the prevalence of sarcopenia in Africa and its characteristics.

STUDY DESIGN AND SETTING: A literature search in PubMed, Web of Science, Google Scholar, and Scopus was conducted in October 2022. All studies reporting the prevalence of sarcopenia in Africa within 15 years were included, and we did an assessment of bias with Hoy et al's risk bias assessment tool. The estimated prevalence of sarcopenia was the outcome and we performed secondary analyses by age, gender, and diagnostic criteria. The random effect model was used for the prevalence estimation. The prevalence of sarcopenia and 95% confidence interval (95% CI) were calculated using the inverse-variance method.

RESULTS: A total of 17 studies met our eligibility criteria, for a study population of 12,690 participants with 44.3% males and 55.7% females. The overall prevalence of sarcopenia was 25% (95% CI: 19-30%). The prevalence of sarcopenia among 50 years old and older was 23% (95% CI: 17-29%). We had a higher prevalence of sarcopenia among males (30%, %95 IC: 20-39%) than females (29%, %95 IC: 21-36%). The prevalence of sarcopenia was different depending on the diagnosis criteria used.

CONCLUSION: The prevalence of sarcopenia in Africa was relatively high. However, the fact that the majority of included studies were hospital-based studies shows the necessity of further community-based studies in order to have a more accurate representation of the situation in the general population.}, } @article {pmid37426441, year = {2023}, author = {Pamphlett, R and Bishop, DP}, title = {The toxic metal hypothesis for neurological disorders.}, journal = {Frontiers in neurology}, volume = {14}, number = {}, pages = {1173779}, pmid = {37426441}, issn = {1664-2295}, abstract = {Multiple sclerosis and the major sporadic neurogenerative disorders, amyotrophic lateral sclerosis, Parkinson disease, and Alzheimer disease are considered to have both genetic and environmental components. Advances have been made in finding genetic predispositions to these disorders, but it has been difficult to pin down environmental agents that trigger them. Environmental toxic metals have been implicated in neurological disorders, since human exposure to toxic metals is common from anthropogenic and natural sources, and toxic metals have damaging properties that are suspected to underlie many of these disorders. Questions remain, however, as to how toxic metals enter the nervous system, if one or combinations of metals are sufficient to precipitate disease, and how toxic metal exposure results in different patterns of neuronal and white matter loss. The hypothesis presented here is that damage to selective locus ceruleus neurons from toxic metals causes dysfunction of the blood-brain barrier. This allows circulating toxicants to enter astrocytes, from where they are transferred to, and damage, oligodendrocytes, and neurons. The type of neurological disorder that arises depends on (i) which locus ceruleus neurons are damaged, (ii) genetic variants that give rise to susceptibility to toxic metal uptake, cytotoxicity, or clearance, (iii) the age, frequency, and duration of toxicant exposure, and (iv) the uptake of various mixtures of toxic metals. Evidence supporting this hypothesis is presented, concentrating on studies that have examined the distribution of toxic metals in the human nervous system. Clinicopathological features shared between neurological disorders are listed that can be linked to toxic metals. Details are provided on how the hypothesis applies to multiple sclerosis and the major neurodegenerative disorders. Further avenues to explore the toxic metal hypothesis for neurological disorders are suggested. In conclusion, environmental toxic metals may play a part in several common neurological disorders. While further evidence to support this hypothesis is needed, to protect the nervous system it would be prudent to take steps to reduce environmental toxic metal pollution from industrial, mining, and manufacturing sources, and from the burning of fossil fuels.}, } @article {pmid37425721, year = {2023}, author = {Angrick, M and Luo, S and Rabbani, Q and Candrea, DN and Shah, S and Milsap, GW and Anderson, WS and Gordon, CR and Rosenblatt, KR and Clawson, L and Maragakis, N and Tenore, FV and Fifer, MS and Hermansky, H and Ramsey, NF and Crone, NE}, title = {Online speech synthesis using a chronically implanted brain-computer interface in an individual with ALS.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, pmid = {37425721}, support = {UH3 NS114439/NS/NINDS NIH HHS/United States ; }, abstract = {Recent studies have shown that speech can be reconstructed and synthesized using only brain activity recorded with intracranial electrodes, but until now this has only been done using retrospective analyses of recordings from able-bodied patients temporarily implanted with electrodes for epilepsy surgery. Here, we report online synthesis of intelligible words using a chronically implanted brain-computer interface (BCI) in a clinical trial participant (ClinicalTrials.gov, NCT03567213) with dysarthria due to amyotrophic lateral sclerosis (ALS). We demonstrate a reliable BCI that synthesizes commands freely chosen and spoken by the user from a vocabulary of 6 keywords originally designed to allow intuitive selection of items on a communication board. Our results show for the first time that a speech-impaired individual with ALS can use a chronically implanted BCI to reliably produce synthesized words that are intelligible to human listeners while preserving the participants voice profile.}, } @article {pmid37425709, year = {2023}, author = {Rhodes, E and Alfa, S and Jin, H and Massimo, L and Elman, L and Amado, D and Baer, M and Quinn, C and McMillan, CT}, title = {Cognitive reserve in ALS: The role of occupational skills and requirements.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, doi = {10.1101/2023.06.21.23291677}, pmid = {37425709}, support = {K08 NS114106/NS/NINDS NIH HHS/United States ; }, abstract = {BACKGROUND: Amyotrophic Lateral Sclerosis (ALS) is a heterogeneous neurodegenerative condition featuring variable degrees of motor decline and cognitive impairment. We test the hypothesis that cognitive reserve (CR), defined by occupational histories involving more complex cognitive demands, may protect against cognitive decline, while motor reserve (MR), defined by working jobs requiring complex motor skills, may protect against motor dysfunction.

METHODS: Individuals with ALS (n=150) were recruited from the University of Pennsylvania's Comprehensive ALS Clinic. Cognitive performance was evaluated using the Edinburgh Cognitive and Behavioral ALS Screen (ECAS), and motor functioning was measured using Penn Upper Motor Neuron (PUMNS) scale and ALS Functional Rating Scales (ALSFRS-R). The Occupational Information Network (O*NET) Database was used to derive 17 factors representing distinct worker characteristics, occupational requirements, and worker requirements, which were related to ECAS, PUMNS, and ALSFRS-R scores using multiple linear regression.

RESULTS: A history of working jobs involving greater reasoning ability (β=2.12, p<.05), social ability (β=1.73, p<.05), analytic skills, (β=3.12, p<.01) and humanities knowledge (β=1.83, p<.01) was associated with better performance on the ECAS, while jobs involving more exposure to environmental hazards (β=-2.57, p<.01) and technical skills (β=-2.16, p<.01) were associated with lower ECAS Total Scores. Jobs involving greater precision skills (β=1.91, p<.05) were associated with greater disease severity on the PUMNS. Findings for the ALSFRS-R did not survive correction for multiple comparisons.

DISCUSSION: Jobs requiring greater reasoning abilities, social skills, and humanities knowledge were related to preserved cognitive functioning consistent with CR, while jobs with greater exposure to environmental hazards and technical demands were linked to poorer cognitive functioning. We did not find evidence of MR as no protective effects of occupational skills and requirements were found for motor symptoms, and jobs involving greater precision skills and reasoning abilities were associated with worse motor functioning. Occupational history provides insight into protective and risk factors for variable degrees of cognitive and motor dysfunction in ALS.}, } @article {pmid37424512, year = {2023}, author = {de Alcântara, C and Cruzeiro, MM and França, MC and Alencar, MA and Jaeger, A and de Araújo, CM and da Gama, NAS and Camargos, ST and de Souza, LC}, title = {A comparative study of cognitive and behavioral profiles between sporadic and type 8 amyotrophic lateral sclerosis.}, journal = {Muscle & nerve}, volume = {68}, number = {3}, pages = {316-322}, doi = {10.1002/mus.27927}, pmid = {37424512}, issn = {1097-4598}, mesh = {Male ; Humans ; Middle Aged ; *Amyotrophic Lateral Sclerosis/diagnosis ; Executive Function ; *Apathy ; Cognition ; Neuropsychological Tests ; }, abstract = {INTRODUCTION/AIMS: Amyotrophic lateral sclerosis (ALS) type 8 (ALS8) is caused by VAPB gene mutations. The differences between neuropsychological and behavioral profiles of patients with sporadic ALS (sALS) and those with ALS8 are unclear. We aimed to compare cognitive performance and behavioral aspects between sALS and ALS8 patients.

METHODS: Our study included 29 symptomatic ALS8 patients (17 men; median age 49 years), 20 sALS patients (12 men; median age 55 years), and 30 healthy controls (16 men; median age 50 years), matched for sex, age, and education. Participants underwent neuropsychological assessments focused on executive functions, visual memory, and facial emotion recognition. Behavioral and psychiatric symptoms were evaluated using the Hospital Anxiety and Depression Scale and the Cambridge Behavioral Inventory.

RESULTS: Clinical groups (sALS and ALS8) exhibited lower global cognitive efficiency and impaired cognitive flexibility, processing speed, and inhibitory control compared with controls. ALS8 and sALS showed similar performance in most executive tests, except for poorer verbal (lexical) fluency in those with sALS. Apathy, anxiety, and stereotypical behaviors were frequent in both clinical groups.

DISCUSSION: sALS and ALS8 patients demonstrated similar deficits in most cognitive domains and had comparable behavioral profiles. These findings should be considered in the care of patients.}, } @article {pmid37424394, year = {2024}, author = {Dratch, L and Owczarzak, J and Mu, W and Cousins, KAQ and Massimo, L and Grossman, M and Erby, L}, title = {The lived experience of reconstructing identity in response to genetic risk of frontotemporal degeneration and amyotrophic lateral sclerosis.}, journal = {Journal of genetic counseling}, volume = {33}, number = {3}, pages = {515-527}, pmid = {37424394}, issn = {1573-3599}, support = {P01 AG066597/AG/NIA NIH HHS/United States ; ZIE HG200353/ImNIH/Intramural NIH HHS/United States ; /HG/NHGRI NIH HHS/United States ; AG066597/AG/NIA NIH HHS/United States ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/psychology ; Female ; Male ; Middle Aged ; Adult ; Genetic Predisposition to Disease ; Aged ; Frontotemporal Lobar Degeneration/genetics/psychology ; }, abstract = {With the increasing availability of predictive genetic testing for adult-onset neurodegenerative conditions, it is imperative that we better understand the impact of learning one's risk status. Frontotemporal degeneration (FTD) is the second most prevalent cause of early-onset dementia. About one-third of patients have an identifiable genetic etiology, and some genetic variants that cause FTD can also cause amyotrophic lateral sclerosis (ALS). To understand individuals' risk perception and broader experience of living at risk, we completed semi-structured telephone interviews with 14 asymptomatic adults who tested positive for a variant known to cause risk for FTD and/or ALS. We conducted a thematic analysis, and within the core topic of identity, we derived three themes: conceptualization of FTD and ALS as a threat to identity, enduring uncertainty and dread, and varying centrality of risk status to identity. FTD and ALS risk raised fundamental issues for participants related to the essence of personhood, challenged them to confront Cartesian dualism (the philosophy of mind-body separation), and exposed how time, relationships, and social roles have affected their understanding of the nature of the self. Our findings provide important insight into how being at genetic risk shapes an individual's identity. We conclude that genetic counseling interventions that allow for identity exploration, anticipatory guidance, and uncertainty management should be utilized when supporting persons at risk.}, } @article {pmid37423671, year = {2023}, author = {Gómez-Sánchez, A and Vitale, R and Devos, O and de Juan, A and Ruckebusch, C}, title = {Kernelizing: A way to increase accuracy in trilinear decomposition analysis of multiexponential signals.}, journal = {Analytica chimica acta}, volume = {1273}, number = {}, pages = {341545}, doi = {10.1016/j.aca.2023.341545}, pmid = {37423671}, issn = {1873-4324}, abstract = {The unmixing of multiexponential decay signals into monoexponential components using soft modelling approaches is a challenging task due to the strong correlation and complete window overlap of the profiles. To solve this problem, slicing methodologies, such as PowerSlicing, tensorize the original data matrix into a three-way data array that can be decomposed based on trilinear models providing unique solutions. Satisfactory results have been reported for different types of data, e.g., nuclear magnetic resonance or time-resolved fluorescence spectra. However, when decay signals are described by only a few sampling (time) points, a significant degradation of the results can be observed in terms of accuracy and precision of the recovered profiles. In this work, we propose a methodology called Kernelizing that provides a more efficient way to tensorize data matrices of multiexponential decays. Kernelizing relies on the invariance of exponential decays, i.e., when convolving a monoexponential decaying function with any positive function of finite width (hereafter called "kernel"), the shape of the decay (determined by the characteristic decay constant) remains unchanged and only the preexponential factor varies. The way preexponential factors are affected across the sample and time modes is linear, and it only depends on the kernel used. Thus, using kernels of different shapes, a set of convolved curves can be obtained for every sample, and a three-way data array generated, for which the modes are sample, time and kernelizing effect. This three-way array can be afterwards analyzed by a trilinear decomposition method, such as PARAFAC-ALS, to resolve the underlying monoexponential profiles. To validate this new approach and assess its performance, we applied Kernelizing to simulated datasets, real time-resolved fluorescence spectra collected on mixtures of fluorophores and fluorescence-lifetime imaging microscopy data. When the measured multiexponential decays feature few sampling points (down to fifteen), more accurate trilinear model estimates are obtained than when using slicing methodologies.}, } @article {pmid37422901, year = {2023}, author = {Zhao, B and Jiang, Q and Lin, J and Wei, Q and Li, C and Hou, Y and Cao, B and Zhang, L and Ou, R and Liu, K and Yang, T and Xiao, Y and Shang, H}, title = {TBK1 variants in Chinese patients with amyotrophic lateral sclerosis: Genetic analysis and clinical features.}, journal = {European journal of neurology}, volume = {30}, number = {10}, pages = {3079-3089}, doi = {10.1111/ene.15973}, pmid = {37422901}, issn = {1468-1331}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics ; *Frontotemporal Dementia/genetics ; East Asian People ; Mutation, Missense ; Asian People/genetics ; Mutation ; Protein Serine-Threonine Kinases/genetics ; }, abstract = {BACKGROUND AND PURPOSE: Haploinsufficiency of TANK-binding kinase 1 (TBK1) loss-of-function (LoF) variants has been shown to be pathogenic in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). However, the genetic spectrum of TBK1 and clinical features of ALS patients with TBK1 variants remain largely unknown in Asians.

METHODS: Genetic analysis was performed on 2011 Chinese ALS patients. Software was used to predict the deleteriousness of missense variants in TBK1. In addition, PubMed, Embase and Web of Science were searched for related literature.

RESULTS: Twenty-six TBK1 variants were identified in 33 of 2011 ALS patients, including six novel LoF variants (0.3%) and 20 rare missense variants, 12 of which were predicted to be deleterious (0.6%). In addition to TBK1 variants, 11 patients had other ALS-related gene variants. Forty-two previous studies found that the frequency of TBK1 variants was 1.81% in ALS/FTD patients. The frequency of TBK1 LoF variants in ALS was 0.5% (Asians 0.4%; Caucasian 0.6%) and that of missense variants was 0.8% (Asians 1.0%; Caucasian 0.8%). ALS patients with TBK1 LoF variants affecting the kinase domain had a significantly younger age of onset than patients carrying LoF variants affecting the coiled coil domains CCD1 and CCD2. FTD has a frequency of 10% in Caucasian ALS patients with TBK1 LoF variants, which was not found in our cohort.

CONCLUSION: Our study expanded the genotypic spectrum of ALS patients with TBK1 variants and found that the clinical manifestations of TBK1 carriers are diverse.}, } @article {pmid37422655, year = {2023}, author = {van Eijk, RPA and van den Berg, LH and Roes, KCB and Tian, L and Lai, TL and Nelson, LM and Li, C and Scowcroft, A and Garcia-Segovia, J and Lu, Y}, title = {Hybrid Controlled Clinical Trials Using Concurrent Registries in Amyotrophic Lateral Sclerosis: A Feasibility Study.}, journal = {Clinical pharmacology and therapeutics}, volume = {114}, number = {4}, pages = {883-892}, doi = {10.1002/cpt.2994}, pmid = {37422655}, issn = {1532-6535}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/drug therapy ; Feasibility Studies ; Research Design ; }, abstract = {Hybrid designs with both randomized arms and an external control cohort preserve key features of randomization and utilize external information to augment clinical trials. In this study, we propose to leverage high-quality, patient-level concurrent registries to enhance clinical trials and illustrate the impact on trial design for amyotrophic lateral sclerosis. The proposed methodology was evaluated in a randomized, placebo-controlled clinical trial. We used patient-level information from a well-defined, population-based registry, that was running parallel to the randomized clinical trial, to identify concurrently nonparticipating, eligible patients who could be matched with trial participants, and integrate them into the statistical analysis. We assessed the impact of the addition of the external controls on the treatment effect estimate, precision, and time to reach a conclusion. During the runtime of the trial, a total of 1,141 registry patients were alive; 473 (41.5%) of them fulfilled the eligibility criteria and 133 (11.7%) were enrolled in the study. A matched control population could be identified among the nonparticipating patients. Augmenting the randomized controls with matched external controls could have avoided unnecessary randomization of 17 patients (-12.8%) as well as reducing the study duration from 30.1 months to 22.6 months (-25.0%). Matching eligible external controls from a different calendar period led to bias in the treatment effect estimate. Hybrid trial designs utilizing a concurrent registry with rigorous matching can minimize bias due to a mismatch in calendar time and differences in standard of care, and may accelerate the development of new treatments.}, } @article {pmid37422580, year = {2024}, author = {Naito, H and Sugimoto, T and Kimoto, K and Abe, T and Ohno, N and Giga, M and Kono, T and Ueno, H and Nomura, E and Maruyama, H}, title = {Detection of episodic nocturnal hypercapnia in patients with neurodegenerative disorders.}, journal = {Sleep & breathing = Schlaf & Atmung}, volume = {28}, number = {1}, pages = {393-399}, pmid = {37422580}, issn = {1522-1709}, mesh = {Humans ; Hypercapnia/diagnosis/epidemiology ; Hypoventilation/diagnosis ; Carbon Dioxide ; *Amyotrophic Lateral Sclerosis/diagnosis/epidemiology ; *Neurodegenerative Diseases/diagnosis/epidemiology ; Biomarkers ; }, abstract = {PURPOSE: Episodic nocturnal hypercapnia (eNH) in transcutaneous carbon dioxide pressure (PtcCO2) corresponding to rapid eye movement sleep hypoventilation is a useful biomarker for detecting nocturnal hypoventilation. However, the relationship between eNH and neurodegenerative diseases with sleep-related breathing disorders (SRBDs) is unknown. The aim of this study was to evaluate the relationship between eNH and nocturnal hypoventilation in neurodegenerative diseases.

METHODS: Patients with neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), multiple system atrophy (MSA), Parkinson's disease, progressive supranuclear palsy, corticobasal syndrome, and idiopathic normal pressure hydrocephalus, were enrolled and received overnight PtcCO2 monitoring. The patients were divided into groups for eNH and sleep-associated hypoventilation (SH) prevalence analysis: A (ALS), B (MSA), and C (others).

RESULTS: Among 110 patients, twenty-three (21%) and 10 (9%) of the patients met eNH and SH criteria, respectively. eNH and SH were significantly more frequent in groups A and B than in C. The prevalence of SH in the patients with eNH was 39% whereas most of patients with SH (90%) presented with eNH. Among patients with daytime carbon dioxide pressure in arterial blood ≤ 45 mmHg, eNH frequency was 13%, whereas none of the patients met SH criteria. The frequency of noninvasive positive pressure ventilation after PtcCO2 monitoring was significantly higher in those with than without eNH.

CONCLUSIONS: eNH is common in patients with MSA and ALS who present with SRBD. eNH with overnight PtcCO2 monitoring is a useful biomarker to detect hypoventilation among neurodegenerative diseases with different SRBD mechanisms.}, } @article {pmid37421736, year = {2023}, author = {Migliorelli, L and Berardini, D and Cela, K and Coccia, M and Villani, L and Frontoni, E and Moccia, S}, title = {A store-and-forward cloud-based telemonitoring system for automatic assessing dysarthria evolution in neurological diseases from video-recording analysis.}, journal = {Computers in biology and medicine}, volume = {163}, number = {}, pages = {107194}, doi = {10.1016/j.compbiomed.2023.107194}, pmid = {37421736}, issn = {1879-0534}, mesh = {Humans ; *Dysarthria/diagnosis ; *Amyotrophic Lateral Sclerosis ; Cloud Computing ; Speech ; Video Recording ; }, abstract = {BACKGROUND AND OBJECTIVES: Patients suffering from neurological diseases may develop dysarthria, a motor speech disorder affecting the execution of speech. Close and quantitative monitoring of dysarthria evolution is crucial for enabling clinicians to promptly implement patients' management strategies and maximizing effectiveness and efficiency of communication functions in term of restoring, compensating or adjusting. In the clinical assessment of orofacial structures and functions, at rest condition or during speech and non-speech movements, a qualitative evaluation is usually performed, throughout visual observation.

METHODS: To overcome limitations posed by qualitative assessments, this work presents a store-and-forward self-service telemonitoring system that integrates, within its cloud architecture, a convolutional neural network (CNN) for analyzing video recordings acquired by individuals with dysarthria. This architecture - called facial landmark Mask RCNN - aims at locating facial landmarks as a prior for assessing the orofacial functions related to speech and examining dysarthria evolution in neurological diseases.

RESULTS: When tested on the Toronto NeuroFace dataset, a publicly available annotated dataset of video recordings from patients with amyotrophic lateral sclerosis (ALS) and stroke, the proposed CNN achieved a normalized mean error equal to 1.79 on localizing the facial landmarks. We also tested our system in a real-life scenario on 11 bulbar-onset ALS subjects, obtaining promising outcomes in terms of facial landmark position estimation.

DISCUSSION AND CONCLUSIONS: This preliminary study represents a relevant step towards the use of remote tools to support clinicians in monitoring the evolution of dysarthria.}, } @article {pmid37421418, year = {2023}, author = {Kim, H and Choi, M and Han, S and Park, SY and Jeong, M and Kim, SR and Hwang, EM and Lee, SG}, title = {Expression patterns of AEG-1 in the normal brain.}, journal = {Brain structure & function}, volume = {228}, number = {7}, pages = {1629-1641}, pmid = {37421418}, issn = {1863-2661}, support = {NRF-2020R1F1A1071525//National Research Foundation of Korea/ ; NRF-2017R1D1A1B03032218//National Research Foundation of Korea/ ; }, mesh = {Animals ; Humans ; Mice ; *Brain/metabolism ; Brain Neoplasms/pathology ; Cell Adhesion Molecules/metabolism ; *Membrane Proteins/genetics/metabolism ; }, abstract = {Astrocyte elevated gene-1 (AEG-1) is a well-known oncogene implicated in various types of human cancers, including brain tumors. Recently, AEG-1 has also been reported to play pivotal roles in glioma-associated neurodegeneration and neurodegenerative diseases like Parkinson's disease and amyotrophic lateral sclerosis. However, the normal physiological functions and expression patterns of AEG-1 in the brain are not well understood. In this study, we investigated the expression patterns of AEG-1 in the normal mouse brain and found that AEG-1 is widely expressed in neurons and neuronal precursor cells, but little in glial cells. We observed differential expression levels of AEG-1 in various brain regions, and its expression was mainly localized in the cell body of neurons rather than the nucleus. Additionally, AEG-1 was expressed in the cytoplasm of Purkinje cells in both the mouse and human cerebellum, suggesting its potential role in this brain region. These findings suggest that AEG-1 may have important functions in normal brain physiology and warrant further investigation. Our results may also shed light on the differential expression patterns of AEG-1 in normal and pathological brains, providing insights into its roles in various neurological disorders.}, } @article {pmid37420383, year = {2022}, author = {Park, S and Simeone, O}, title = {Speeding up Training of Linear Predictors for Multi-Antenna Frequency-Selective Channels via Meta-Learning.}, journal = {Entropy (Basel, Switzerland)}, volume = {24}, number = {10}, pages = {}, pmid = {37420383}, issn = {1099-4300}, support = {725731/ERC_/European Research Council/International ; }, abstract = {An efficient data-driven prediction strategy for multi-antenna frequency-selective channels must operate based on a small number of pilot symbols. This paper proposes novel channel-prediction algorithms that address this goal by integrating transfer and meta-learning with a reduced-rank parametrization of the channel. The proposed methods optimize linear predictors by utilizing data from previous frames, which are generally characterized by distinct propagation characteristics, in order to enable fast training on the time slots of the current frame. The proposed predictors rely on a novel long short-term decomposition (LSTD) of the linear prediction model that leverages the disaggregation of the channel into long-term space-time signatures and fading amplitudes. We first develop predictors for single-antenna frequency-flat channels based on transfer/meta-learned quadratic regularization. Then, we introduce transfer and meta-learning algorithms for LSTD-based prediction models that build on equilibrium propagation (EP) and alternating least squares (ALS). Numerical results under the 3GPP 5G standard channel model demonstrate the impact of transfer and meta-learning on reducing the number of pilots for channel prediction, as well as the merits of the proposed LSTD parametrization.}, } @article {pmid37418099, year = {2023}, author = {Moglia, C and Palumbo, F and Veronese, S and , and Calvo, A}, title = {Withdrawal of mechanical ventilation in amyotrophic lateral sclerosis patients: a multicenter Italian survey.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {44}, number = {12}, pages = {4349-4357}, pmid = {37418099}, issn = {1590-3478}, support = {RF-2016-02362405//Ministero della Salute/ ; 2017SNW5MB//Ministero dell'Istruzione, dell'Università e della Ricerca/ ; FP7/2007-2013//Seventh Framework Programme/ ; 101017598//Horizon 2020/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy ; Respiration, Artificial ; *Terminal Care/methods ; Delivery of Health Care ; *Neurology ; }, abstract = {BACKGROUND: Law 219/2017 was approved in Italy in December 2017, after a years-long debate on the autonomy of healthcare choices. This Law, for the first time in Italian legislation, guarantees the patient's right to request for withdrawal of life-sustaining treatments, including mechanical ventilation (MV).

OBJECTIVE: To investigate the current status of MV withdrawal in amyotrophic lateral sclerosis (ALS) patients in Italy and to assess the impact of Law 219/2017 on this practice.

METHODS: We conducted a Web-based survey, addressed to Italian neurologists with expertise in ALS care, and members of the Motor Neuron Disease Study Group of the Italian Society of Neurology.

RESULTS: Out of 40 ALS Italian centers, 34 (85.0%) responded to the survey. Law 219/2017 was followed by an increasing trend in MV withdrawals, and a significant increase of neurologists involved in this procedure (p 0.004). However, variations across Italian ALS centers were observed, regarding the inconsistent involvement of community health services and palliative care (PC) services, and the intervention and composition of the multidisciplinary team.

CONCLUSIONS: Law 219/2017 has had a positive impact on the practice of MV withdrawal in ALS patients in Italy. The recent growing public attention on end-of-life care choices, along with the cultural and social changes in Italy, requires further regulatory frameworks that strengthen tools for self-determination, increased investment of resources in community and PC health services, and practical recommendations and guidelines for health workers involved.}, } @article {pmid37414530, year = {2023}, author = {Pinkerton, M and Lourenco, G and Pacheco, MT and Halliday, GM and Kiernan, MC and Tan, RH}, title = {Survival in sporadic ALS is associated with lower p62 burden in the spinal cord.}, journal = {Journal of neuropathology and experimental neurology}, volume = {82}, number = {9}, pages = {769-773}, pmid = {37414530}, issn = {1554-6578}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/pathology ; Motor Neurons/pathology ; Spinal Cord/pathology ; Inclusion Bodies/pathology ; }, abstract = {The autophagy marker p62 appears as a consistent component of pathological aggregates in amyotrophic lateral sclerosis (ALS) and its modulation to facilitate protein degradation has been proposed as a potential therapeutic target. Importantly, recent studies have implicated diffuse phosphorylated TDP-43 inclusions that are immuno-negative for p62 in more rapid disease, highlighting the need for better understanding of p62 involvement in ALS pathogenesis. The present study set out to assess p62 pathology in the motor neurons of 31 patients with sporadic ALS that had either a short (<2 years) or longer (4-7 years) disease duration to determine its association with pTDP-43 pathology, motor neuron loss, and survival in sporadic disease. Our results identified significantly more cytoplasmic p62 aggregates in the spinal cord of patients with a shorter survival. Disease duration demonstrated a negative association with p62 burden and density of remaining motor neurons in the spinal cord, suggesting that survival in sporadic ALS is associated with the successful clearance of lower motor neurons with p62 aggregates. These findings implicate the autophagy pathway in ALS survival and provide support for further study of p62 as a potential prognostic biomarker in ALS.}, } @article {pmid37410912, year = {2023}, author = {Bodin, A and Greibill, L and Gouju, J and Letournel, F and Pozzi, S and Julien, JP and Renaud, L and Bohl, D and Millecamps, S and Verny, C and Cassereau, J and Lenaers, G and Chevrollier, A and Tassin, AM and Codron, P}, title = {Transactive response DNA-binding protein 43 is enriched at the centrosome in human cells.}, journal = {Brain : a journal of neurology}, volume = {146}, number = {9}, pages = {3624-3633}, pmid = {37410912}, issn = {1460-2156}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism ; DNA-Binding Proteins/genetics/metabolism ; *TDP-43 Proteinopathies/pathology ; *Frontotemporal Lobar Degeneration/pathology ; Centrosome/metabolism/pathology ; }, abstract = {The centrosome, as the main microtubule organizing centre, plays key roles in cell polarity, genome stability and ciliogenesis. The recent identification of ribosomes, RNA-binding proteins and transcripts at the centrosome suggests local protein synthesis. In this context, we hypothesized that TDP-43, a highly conserved RNA binding protein involved in the pathophysiology of amyotrophic lateral sclerosis and frontotemporal lobar degeneration, could be enriched at this organelle. Using dedicated high magnification sub-diffraction microscopy on human cells, we discovered a novel localization of TDP-43 at the centrosome during all phases of the cell cycle. These results were confirmed on purified centrosomes by western blot and immunofluorescence microscopy. In addition, the co-localization of TDP-43 and pericentrin suggested a pericentriolar enrichment of the protein, leading us to hypothesize that TDP-43 might interact with local mRNAs and proteins. Supporting this hypothesis, we found four conserved centrosomal mRNAs and 16 centrosomal proteins identified as direct TDP-43 interactors. More strikingly, all the 16 proteins are implicated in the pathophysiology of TDP-43 proteinopathies, suggesting that TDP-43 dysfunction in this organelle contributes to neurodegeneration. This first description of TDP-43 centrosomal enrichment paves the way for a more comprehensive understanding of TDP-43 physiology and pathology.}, } @article {pmid37408276, year = {2023}, author = {Hosaka, T and Tsuji, H and Kwak, S}, title = {Roles of Aging, Circular RNAs, and RNA Editing in the Pathogenesis of Amyotrophic Lateral Sclerosis: Potential Biomarkers and Therapeutic Targets.}, journal = {Cells}, volume = {12}, number = {10}, pages = {}, pmid = {37408276}, issn = {2073-4409}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/therapy/metabolism ; RNA, Circular/genetics/metabolism ; RNA Editing/genetics ; RNA/genetics/metabolism ; Aging/genetics ; Biomarkers/metabolism ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is an incurable motor neuron disease caused by upper and lower motor neuron death. Despite advances in our understanding of ALS pathogenesis, effective treatment for this fatal disease remains elusive. As aging is a major risk factor for ALS, age-related molecular changes may provide clues for the development of new therapeutic strategies. Dysregulation of age-dependent RNA metabolism plays a pivotal role in the pathogenesis of ALS. In addition, failure of RNA editing at the glutamine/arginine (Q/R) site of GluA2 mRNA causes excitotoxicity due to excessive Ca[2+] influx through Ca[2+]-permeable α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors, which is recognized as an underlying mechanism of motor neuron death in ALS. Circular RNAs (circRNAs), a circular form of cognate RNA generated by back-splicing, are abundant in the brain and accumulate with age. Hence, they are assumed to play a role in neurodegeneration. Emerging evidence has demonstrated that age-related dysregulation of RNA editing and changes in circRNA expression are involved in ALS pathogenesis. Herein, we review the potential associations between age-dependent changes in circRNAs and RNA editing, and discuss the possibility of developing new therapies and biomarkers for ALS based on age-related changes in circRNAs and dysregulation of RNA editing.}, } @article {pmid37408187, year = {2023}, author = {Zimyanin, VL and Pielka, AM and Glaß, H and Japtok, J and Großmann, D and Martin, M and Deussen, A and Szewczyk, B and Deppmann, C and Zunder, E and Andersen, PM and Boeckers, TM and Sterneckert, J and Redemann, S and Storch, A and Hermann, A}, title = {Live Cell Imaging of ATP Levels Reveals Metabolic Compartmentalization within Motoneurons and Early Metabolic Changes in FUS ALS Motoneurons.}, journal = {Cells}, volume = {12}, number = {10}, pages = {}, pmid = {37408187}, issn = {2073-4409}, support = {S10 OD025156/OD/NIH HHS/United States ; R01 NS111220/NS/NINDS NIH HHS/United States ; R01 NS091617/NS/NINDS NIH HHS/United States ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism ; Motor Neurons/metabolism ; Mutation ; Mitochondria/metabolism ; Adenosine Triphosphate/metabolism ; RNA-Binding Protein FUS/genetics/metabolism/pharmacology ; }, abstract = {Motoneurons are one of the most energy-demanding cell types and a primary target in Amyotrophic lateral sclerosis (ALS), a debilitating and lethal neurodegenerative disorder without currently available effective treatments. Disruption of mitochondrial ultrastructure, transport, and metabolism is a commonly reported phenotype in ALS models and can critically affect survival and the proper function of motor neurons. However, how changes in metabolic rates contribute to ALS progression is not fully understood yet. Here, we utilize hiPCS-derived motoneuron cultures and live imaging quantitative techniques to evaluate metabolic rates in fused in sarcoma (FUS)-ALS model cells. We show that differentiation and maturation of motoneurons are accompanied by an overall upregulation of mitochondrial components and a significant increase in metabolic rates that correspond to their high energy-demanding state. Detailed compartment-specific live measurements using a fluorescent ATP sensor and FLIM imaging show significantly lower levels of ATP in the somas of cells carrying FUS-ALS mutations. These changes lead to the increased vulnerability of diseased motoneurons to further metabolic challenges with mitochondrial inhibitors and could be due to the disruption of mitochondrial inner membrane integrity and an increase in its proton leakage. Furthermore, our measurements demonstrate heterogeneity between axonal and somatic compartments, with lower relative levels of ATP in axons. Our observations strongly support the hypothesis that mutated FUS impacts the metabolic states of motoneurons and makes them more susceptible to further neurodegenerative mechanisms.}, } @article {pmid37408045, year = {2023}, author = {Morris, JL and Chalkley, AE and Helme, ZE and Timms, O and Young, E and McLoughlin, GM and Bartholomew, JB and Daly-Smith, A}, title = {Initial insights into the impact and implementation of Creating Active Schools in Bradford, UK.}, journal = {The international journal of behavioral nutrition and physical activity}, volume = {20}, number = {1}, pages = {80}, pmid = {37408045}, issn = {1479-5868}, mesh = {Humans ; *School Health Services ; *Schools ; Exercise ; Focus Groups ; United Kingdom ; }, abstract = {BACKGROUND: Few whole-school physical activity programmes integrate implementation science frameworks within the design, delivery, and evaluation. As a result, knowledge of the key factors that support implementation at scale is lacking. The Creating Active Schools (CAS) programme was co-designed and is underpinned by the Capability, Opportunity, Motivation and Behaviour (COM-B) model and the Consolidated Framework for Implementation Research (CFIR). The study aims to understand the initial impact and implementation of CAS in Bradford over 9 months using McKay's et al.'s (2019) implementation evaluation roadmap.

METHODS: Focus groups and interviews were conducted with school staff (n = 30, schools = 25), CAS Champions (n = 9), and the CAS strategic lead (n = 1). Qualitative data were analysed both inductively and deductively. The deductive analysis involved coding data into a priori themes based on McKay et al's implementation evaluation roadmap, using a codebook approach to thematic analysis. The inductive analysis included producing initial codes and reviewing themes before finalising.

RESULTS: Identified themes aligned into three categories: (i) key ingredients for successful adoption and implementation of CAS, (ii) CAS implementation: challenges and solutions, and (iv) the perceived effectiveness of CAS at the school level. This included the willingness of schools to adopt and implement whole-school approaches when they are perceived as high quality and aligned with current school values. The programme implementation processes were seen as supportive; schools identified and valued the step-change approach to implementing CAS long-term. Formal and informal communities of practice provided "safe spaces" for cross-school support. Conversely, challenges persisted with gaining broader reach within schools, school staff's self-competence and shifting school culture around physical activity. This resulted in varied uptake between and within schools.

CONCLUSIONS: This study provides novel insights into the implementation of CAS, with outcomes aligning to the adoption, reach, and sustainability. Successful implementation of CAS was underpinned by determinants including acceptability, intervention complexity, school culture and school stakeholders' perceived self-efficacy. The combination of McKay's evaluation roadmap and CFIR establishes a rigorous approach for evaluating activity promotion programmes underpinned by behavioural and implementation science. Resultantly this study offers originality and progression in understanding the implementation and effectiveness of whole-school approaches to physical activity.}, } @article {pmid37407098, year = {2023}, author = {Kious, BM}, title = {Medical Assistance in Dying in Neurology.}, journal = {Neurologic clinics}, volume = {41}, number = {3}, pages = {443-454}, doi = {10.1016/j.ncl.2023.03.002}, pmid = {37407098}, issn = {1557-9875}, mesh = {Humans ; *Suicide, Assisted/psychology ; *Alzheimer Disease ; Medical Assistance ; *Neurology ; }, abstract = {An increasing number of jurisdictions have legalized medical assistance in dying (MAID) with significant variation in the procedures and eligibility criteria used. In the United States, MAID is available for persons with terminal illnesses but is frequently sought by persons with neurologic conditions. Persons with conditions that cause cognitive impairment, such as Alzheimer dementia, are often ineligible for MAID, as their illness is not considered terminal in its early stages, whereas in later stages, they may have impaired decision-making capacity.}, } @article {pmid37402805, year = {2023}, author = {Kiani, L}, title = {Electrophysiology test for early ALS diagnosis.}, journal = {Nature reviews. Neurology}, volume = {19}, number = {8}, pages = {459}, pmid = {37402805}, issn = {1759-4766}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis ; Motor Neurons ; Electrophysiology ; }, } @article {pmid37402803, year = {2023}, author = {Kiani, L}, title = {Fatty acids might slow ALS progression.}, journal = {Nature reviews. Neurology}, volume = {19}, number = {8}, pages = {459}, pmid = {37402803}, issn = {1759-4766}, mesh = {Humans ; *Fatty Acids ; *Amyotrophic Lateral Sclerosis/genetics ; Disease Progression ; }, } @article {pmid37401984, year = {2023}, author = {Gomes, BPFA and Berber, VB and Chiarelli-Neto, VM and Aveiro, E and Chapola, RC and Passini, MRZ and Lopes, EM and Chen, T and Paster, BJ}, title = {Microbiota present in combined endodontic-periodontal diseases and its risks for endocarditis.}, journal = {Clinical oral investigations}, volume = {27}, number = {8}, pages = {4757-4771}, pmid = {37401984}, issn = {1436-3771}, mesh = {Humans ; *Periodontal Diseases ; *Endocarditis ; Bacteria ; Periodontal Pocket/microbiology ; *Microbiota ; }, abstract = {INTRODUCTION: Infective endocarditis (IE) is an inflammatory disease usually caused by bacteria that enter the bloodstream and establish infections in the inner linings or valves of the heart, including blood vessels. Despite the availability of modern antimicrobial and surgical treatments, IE continues to cause substantial morbidity and mortality. Oral microbiota is considered one of the most significant risk factors for IE. The objective of this study was to evaluate the microbiota present in root canal (RC) and periodontal pocket (PP) clinical samples in cases with combined endo-periodontal lesions (EPL) to detect species related to IE using NGS.

METHODS: Microbial samples were collected from 15 RCs and their associated PPs, also from 05 RCs with vital pulp tissues (negative control, NC). Genomic studies associated with bioinformatics, combined with structuring of a database (genetic sequences of bacteria reported for infective endocarditis), allowed for the assessment of the microbial community at both sites. Functional prediction was conducted using PICRUSt2.

RESULTS: Parvimonas, Streptococcus, and Enterococcus were the major genera detected in the RCs and PPs. A total of 79, 96, and 11 species were identified in the RCs, PPs, and NCs, respectively. From them, a total of 34 species from RCs, 53 from PPs, and 2 from NCs were related to IE. Functional inference demonstrated that CR and PP microbiological profiles may not be the only risk factors for IE but may also be associated with systemic diseases, including myocarditis, human cytomegalovirus infection, bacterial invasion of epithelial cells, Huntington's disease, amyotrophic lateral sclerosis, and hypertrophic cardiomyopathy. Additionally, it was possible to predict antimicrobial resistance variants for broad-spectrum drugs, including ampicillin, tetracycline, and macrolides.

CONCLUSION: Microorganisms present in the combined EPL may not be the only risk factor for IE but also for systemic diseases. Antimicrobial resistance variants for broad-spectrum drugs were inferred based on PICRUSt-2. State-of-the-art sequencing combined with bioinformatics has proven to be a powerful tool for conducting studies on microbial communities and could considerably assist in the diagnosis of serious infections.

CLINICAL RELEVANCE: Few studies have investigated the microbiota in teeth compromised by combined endo-periodontal lesions (EPL), but none have correlated the microbiological findings to any systemic condition, particularly IE, using NGS techniques. In such cases, the presence of apical periodontitis and periodontal disease can increase IE risk in susceptible patients.}, } @article {pmid37401737, year = {2024}, author = {Brewer, MK and Torres, P and Ayala, V and Portero-Otin, M and Pamplona, R and Andrés-Benito, P and Ferrer, I and Gentry, MS and Guinovart, JJ and Duran, J}, title = {Glycogen accumulation modulates life span in a mouse model of amyotrophic lateral sclerosis.}, journal = {Journal of neurochemistry}, volume = {168}, number = {5}, pages = {744-759}, pmid = {37401737}, issn = {1471-4159}, support = {P01 NS097197/NS/NINDS NIH HHS/United States ; R35 NS116824/NS/NINDS NIH HHS/United States ; 754510//H2020 Marie Skłodowska-Curie Actions/ ; //Ministerio de Ciencia e Innovación/ ; PI20/00155//Ministerio de Ciencia, Innovación y Universidades/ ; BFU2017-84345-P//Ministerio de Ciencia, Innovación y Universidades/ ; PID2020-118699GB-I00//Ministerio de Ciencia, Innovación y Universidades/ ; //Ministerio de Economía y Competitividad/ ; //Ministerio de Universidades/ ; P01 NS097197/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; *Amyotrophic Lateral Sclerosis/metabolism/pathology/genetics ; *Glycogen/metabolism ; Mice ; *Mice, Transgenic ; *Disease Models, Animal ; *Longevity ; *Spinal Cord/metabolism/pathology ; *Astrocytes/metabolism ; Male ; Mice, Inbred C57BL ; Humans ; Superoxide Dismutase-1/genetics/metabolism ; Female ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by the progressive loss of motor neurons in the spinal cord. Glial cells, including astrocytes and microglia, have been shown to contribute to neurodegeneration in ALS, and metabolic dysfunction plays an important role in the progression of the disease. Glycogen is a soluble polymer of glucose found at low levels in the central nervous system that plays an important role in memory formation, synaptic plasticity, and the prevention of seizures. However, its accumulation in astrocytes and/or neurons is associated with pathological conditions and aging. Importantly, glycogen accumulation has been reported in the spinal cord of human ALS patients and mouse models. In the present work, using the SOD1[G93A] mouse model of ALS, we show that glycogen accumulates in the spinal cord and brainstem during symptomatic and end stages of the disease and that the accumulated glycogen is associated with reactive astrocytes. To study the contribution of glycogen to ALS progression, we generated SOD1[G93A] mice with reduced glycogen synthesis (SOD1[G93A] GS[het] mice). SOD1[G93A] GS[het] mice had a significantly longer life span than SOD1[G93A] mice and showed lower levels of the astrocytic pro-inflammatory cytokine Cxcl10, suggesting that the accumulation of glycogen is associated with an inflammatory response. Supporting this, inducing an increase in glycogen synthesis reduced life span in SOD1[G93A] mice. Altogether, these results suggest that glycogen in reactive astrocytes contributes to neurotoxicity and disease progression in ALS.}, } @article {pmid37399804, year = {2023}, author = {Hanhisuanto, M and Solje, E and Jokela, M and Sipilä, JOT}, title = {Amyotrophic Lateral Sclerosis in Southwestern and Eastern Finland.}, journal = {Neuroepidemiology}, volume = {57}, number = {4}, pages = {238-245}, doi = {10.1159/000531238}, pmid = {37399804}, issn = {1423-0208}, mesh = {Male ; Humans ; Female ; Aged ; *Amyotrophic Lateral Sclerosis/diagnosis/epidemiology/genetics ; Riluzole ; Finland/epidemiology ; C9orf72 Protein/genetics ; Phenotype ; }, abstract = {INTRODUCTION: The incidence of amyotrophic lateral sclerosis (ALS) worldwide is approximately 1-2.6/1,000,000 and prevalence is 5-6/100,000. ALS has been suggested to be relatively common in Finland, but epidemiological information on the subject is scarce and outdated.

MATERIAL AND METHODS: Patients with ALS diagnostic codes were identified from mandatory administrative registries in the provinces of Southwestern Finland (population circa 430,000) and North Karelia (population circa 170,000), together comprising 11.7% of the total population of Finland. The diagnoses were verified, and data were extracted by reviewing the patient records. Incidence period was 2010-2018, and the prevalence date was December 31, 2018. Age-standardization was performed using the European Standard Population 2013 (ESP2013).

RESULTS: Overall crude incidence of ALS was 4.2/100,000 person-years in Southwestern Finland (ESP2013: 4.0/100,000) and 5.6/100,000 person-years in North Karelia (ESP2013: 4.8/100,000), while crude prevalences were 11.9/100,000 (ESP2013: 10.5/100,000) and 10.9/100,000 (ESP2013: 9.3/100,000), respectively. Mean age at diagnosis was 65.5-71.6 years in women (higher in Southwestern Finland compared to North Karelia, p = 0.003) and 64.7-67.3 years in men (no difference between provinces, p = 0.39). The diagnosis had been made in 50% before the age of 70 years in Southwestern Finland and before the age of 65 years in 51% in North Karelia. Genetic testing had been conducted in 28% of all patients with the most common findings being SOD1 and C9orf72. After the diagnosis, mean survival was 2.0-2.7 and median survival 1.3-1.4 years. Onset phenotype (p < 0.001), age at diagnosis (p < 0.001), and genotype (p = 0.001) predicted survival. Riluzole had been used by 25% of patients and tracheostomy and invasive ventilation (TIV) had been performed in <1%.

CONCLUSIONS: Both incidence and prevalence of ALS in Finland are among the highest in the world but with some notable differences between the eastern and southwestern parts of the country. Low median life expectancy may be related to the advanced age of patients and the high prevalence of C9orf72 repeat expansion in Finland as well infrequent use of TIV and riluzole.}, } @article {pmid37399802, year = {2023}, author = {Pannek, J and Mahler, J and Wöllner, J and Krebs, J}, title = {Satisfaction with Homeopathic Service and Care for Persons with Spinal Cord Injury.}, journal = {Complementary medicine research}, volume = {30}, number = {5}, pages = {408-414}, doi = {10.1159/000531658}, pmid = {37399802}, issn = {2504-2106}, mesh = {Humans ; Cross-Sectional Studies ; *Homeopathy ; Surveys and Questionnaires ; Switzerland ; }, abstract = {BACKGROUND: The aim of the study was to investigate the satisfaction of individuals with spinal cord injury (SCI) with a homeopathic service at an SCI rehabilitation center.

PATIENTS AND METHODS: A cross-sectional questionnaire study was performed at an SCI rehabilitation center in Switzerland. It included patients with chronic SCI who presented themselves to a homeopathic service offered by the hospital in a 12-months period. The participants filled in standardized questionnaires in German: "Measure Yourself Medical Outcome Profile" (MYMOP), Treatment Satisfaction Questionnaire for Medication (TSQM-9), the European Project on Patient Evaluation of General Practice Care (EUROPEP) questionnaire, and a self-administered questionnaire.

RESULTS: The data of 14 patients were analyzed. Symptom severity as well as bother by the symptoms that led to homeopathic treatment decreased under homeopathic treatment (severity: from 4.3 to 3.3; bother: from 4.2 to 2.9) and remained lower over time (severity: 2.6; bother: 2.7), suggesting a sustained effect. Irrespective of the test instrument used, satisfaction rates were higher for homeopathic service than for homeopathic medication, which was rated as successful by 50% of the participants.

CONCLUSION: Persons with SCI suffering from secondary complications of SCI who accessed homeopathic care reported high satisfaction rates with the service. Therefore, homeopathic service can be considered as an additive measure in persons with SCI suffering from recurrent symptoms.

UNLABELLED: HintergrundEvaluierung der Zufriedenheit von Personen mit Querschnittlähmung (QSL) mit einer homöopathischen Betreuung an einem Rehabilitationszentrum für QSL.Patient*innen und MethodikAn einem Rehabilitationszentrum für QSL in der Schweiz wurde eine Querschnittserhebung mittels Fragebögen durchgeführt. Eingeschlossen wurden Personen mit chronischer QSL, die sich in einer von der Klinik angebotenen homöopathischen Sprechstunde in einem 12-Monats-Intervall vorstellten. Die Teilnehmenden füllten standardisierte Fragebogen in deutscher Sprache aus: "Measure Yourself Medical Outcome Profile" (MYMOP), Treatment Satisfaction Questionnaire for Medication (TSQM-9), den "European Project on Patient Evaluation of General Practice Care (EUROPEP)" Fragebogen sowie einen selbst-erstellten Fragebogen.ErgebnisseDie Daten von 14 Teilnehmenden wurden ausgewertet. Der Schweregrad der Symptome sowie die Belastung durch die Symptome die zur homöopathischen Behandlung geführt haben, wurden unter der homöopathischen Therapie geringer (Schweregrad: von 4.3 auf 3.3; Belastung: von 4.2 auf 2.9) und blieben über den Untersuchungszeitraum geringer (Schweregrad: 2.6; Belastung 2.7), was einen anhaltenden Effekt nahelegt. Unabhängig von dem verwendeten Testinstrument waren die Zufriedenheitsraten für die homöopathische Betreuung höher als diejenigen für die homöopathische Medikation, die von 50% der Teilnehmenden als erfolgreich bewertet wurde.SchlussfolgerungPersonen mit QSL, die wegen Sekundärkomplikationen eine homöopathische Sprechstunde aufsuchten, berichteten eine hohe Zufriedenheit mit dieser Betreuung. Daher kann eine homöopathische Betreuung als zusätzliche Massnahme bei Personen mit QSL mit persistierender Symptomatik in Betracht gezogen werden.}, } @article {pmid37399380, year = {2023}, author = {Pérez-Cabello, JA and Silvera-Carrasco, L and Franco, JM and Capilla-González, V and Armaos, A and Gómez-Lima, M and García-García, R and Yap, XW and Leal-Lasarte, M and Lall, D and Baloh, RH and Martínez, S and Miyata, Y and Tartaglia, GG and Sawarkar, R and García-Domínguez, M and Pozo, D and Roodveldt, C}, title = {MAPK/MAK/MRK overlapping kinase (MOK) controls microglial inflammatory/type-I IFN responses via Brd4 and is involved in ALS.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {120}, number = {28}, pages = {e2302143120}, pmid = {37399380}, issn = {1091-6490}, support = {MC_UU_00025/8/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Animals ; Mice ; *Amyotrophic Lateral Sclerosis/metabolism ; Disease Models, Animal ; Microglia/metabolism ; *Neurodegenerative Diseases/metabolism ; Nuclear Proteins/metabolism ; Transcription Factors/genetics/metabolism ; *Bromodomain Containing Proteins/genetics/metabolism ; *Mitogen-Activated Protein Kinases/metabolism ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal and incurable neurodegenerative disease affecting motor neurons and characterized by microglia-mediated neurotoxic inflammation whose underlying mechanisms remain incompletely understood. In this work, we reveal that MAPK/MAK/MRK overlapping kinase (MOK), with an unknown physiological substrate, displays an immune function by controlling inflammatory and type-I interferon (IFN) responses in microglia which are detrimental to primary motor neurons. Moreover, we uncover the epigenetic reader bromodomain-containing protein 4 (Brd4) as an effector protein regulated by MOK, by promoting Ser[492]-phospho-Brd4 levels. We further demonstrate that MOK regulates Brd4 functions by supporting its binding to cytokine gene promoters, therefore enabling innate immune responses. Remarkably, we show that MOK levels are increased in the ALS spinal cord, particularly in microglial cells, and that administration of a chemical MOK inhibitor to ALS model mice can modulate Ser[492]-phospho-Brd4 levels, suppress microglial activation, and modify the disease course, indicating a pathophysiological role of MOK kinase in ALS and neuroinflammation.}, } @article {pmid37399127, year = {2023}, author = {Shi, L and Li, X and Xue, L and Zhang, J and Huang, B and Sun, Z and Zhang, Z and Dai, X and Han, S and Dong, W and Zhang, X}, title = {Creation of herbicide-resistance in allotetraploid peanut using CRISPR/Cas9-meditated cytosine base-editing.}, journal = {Plant biotechnology journal}, volume = {21}, number = {10}, pages = {1923-1925}, pmid = {37399127}, issn = {1467-7652}, mesh = {Arachis/genetics ; CRISPR-Cas Systems/genetics ; Cytosine ; *Fabaceae ; *Herbicides ; Gene Editing ; }, } @article {pmid37399044, year = {2023}, author = {Hokkoku, K and Tsukamoto, H and Uchida, Y and Gatto, DM and Sonoo, M}, title = {Different Tendencies in Muscle Ultrasound Characteristic in Amyotrophic Lateral Sclerosis and Chronic Inflammatory Demyelinating Polyradiculoneuropathy.}, journal = {Journal of clinical neurophysiology : official publication of the American Electroencephalographic Society}, volume = {40}, number = {5}, pages = {450-455}, doi = {10.1097/WNP.0000000000000898}, pmid = {37399044}, issn = {1537-1603}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnostic imaging ; *Polyradiculoneuropathy, Chronic Inflammatory Demyelinating/diagnostic imaging ; Action Potentials/physiology ; Muscle, Skeletal/innervation ; Arm ; Neural Conduction/physiology ; }, abstract = {INTRODUCTION: The difference in muscle ultrasound (MUS) characteristics in primary axonal degeneration and demyelination has not been well established. The authors aimed to investigate the subject based on the correlation between MUS findings (echo intensity and muscle thickness) and compound muscle action potential (CMAP) amplitude in amyotrophic lateral sclerosis (ALS) and chronic inflammatory demyelinating polyradiculoneuropathy.

METHODS: Fifteen patients with ALS and 16 patients with chronic inflammatory demyelinating polyradiculoneuropathy were examined. For each patient, echo intensity and muscle thickness of the abductor pollicis brevis, abductor digiti minimi, and first dorsal interosseous muscles were investigated. Compound muscle action potential amplitudes were measured by median and ulnar nerve conduction studies.

RESULTS: In total, 45 muscles were evaluated in each group. The ALS group showed a linear correlation between the MUS finding and CMAP amplitude (rs = -0.70 and 0.59 for echo intensity and muscle thickness, respectively), whereas the chronic inflammatory demyelinating polyradiculoneuropathy group showed a weaker correlation than the ALS group (rs = -0.32 for echo intensity and rs = 0.34 for muscle thickness).

CONCLUSIONS: The relationship between MUS abnormalities and CMAP amplitude showed different tendencies in ALS and chronic inflammatory demyelinating polyradiculoneuropathy. The results suggested that MUS abnormalities substantially reflect the muscle function in primary axonal degeneration, whereas a discrepancy between MUS findings and muscle function can be frequently seen in demyelination; specifically, MUS findings tend to be normal even though CMAP showed a reduction. These tendencies originating from underlying pathophysiology should be considered when MUS findings are used as biomarkers of disease severity.}, } @article {pmid37398206, year = {2023}, author = {Acharya, A and Ambikan, AT and Thurman, M and Malik, MR and Dyavar, SR and Végvári, Á and Neogi, U and Byrareddy, SN}, title = {Proteomic landscape of astrocytes and pericytes infected with HIV/SARS-CoV-2 mono/co-infection, impacting on neurological complications.}, journal = {Research square}, volume = {}, number = {}, pages = {}, pmid = {37398206}, issn = {2693-5015}, support = {R01 DA052845/DA/NIDA NIH HHS/United States ; }, abstract = {BACKGROUND: Although most individuals recover from coronavirus disease 2019 (COVID-19) within a few weeks, some people continue to experience a wide range of symptoms known as post-acute sequelae of SARS-CoV-2 (PASC) or long COVID. Majority of patients with PASC develop neurological disorders like brain fog, fatigue, mood swings, sleep disorders, loss of smell and test among others collectively called neuro-PASC. While the people living with HIV (PWH) do not have a higher risk of developing severe disease and mortality/morbidity due to COVID-19. As a large section of PWH suffered from HIV-associated neurocognitive disorders (HAND), it is essential to understand the impact of neuro-PASC on people with HAND. In pursuit of this, we infected HIV/SARS-CoV-2 alone or together in primary human astrocytes and pericytes and performed proteomics to understand the impact of co-infection in the central nervous system.

METHODS: Primary human astrocytes and pericytes were infected with SARS-CoV-2 or HIV or HIV + SARS-CoV-2. The concentration of HIV and SARS-CoV-2 genomic RNA in the culture supernatant was quantified using reverse transcriptase quantitative real time polymerase chain reaction (RT-qPCR). This was followed by a quantitative proteomics analysis of mock, HIV, SARS-CoV-2, and HIV + SARS-CoV-2 infected astrocytes and pericytes to understand the impact of the virus in CNS cell types.

RESULTS: Both healthy and HIV-infected astrocytes and pericytes support abortive/low level of SARS-CoV-2 replication. In both mono-infected and co-infected cells, we observe a modest increase in the expression of SARS-CoV-2 host cell entry factors (ACE2, TMPRSS2, NRP1, and TRIM28) and inflammatory mediators (IL-6, TNF-α, IL-1β and IL-18). Quantitative proteomic analysis has identified uniquely regulated pathways in mock vs SARS-CoV-2, mock vs HIV + SARS-CoV-2, and HIV vs HIV + SARS-CoV-2 infected astrocytes and pericytes. The gene set enrichment analysis revealed that the top ten enriched pathways are linked to several neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis.

CONCLUSIONS: Our study emphasizes the significance of long-term monitoring of patients co-infected with HIV and SARS-CoV-2 to detect and understand the development of neurological abnormalities. By unraveling the molecular mechanisms involved, we can identify potential targets for future therapeutic interventions.}, } @article {pmid37398081, year = {2023}, author = {Funes, S and Gadd, DH and Mosqueda, M and Zhong, J and Jung, J and Shankaracharya, and Unger, M and Cameron, D and Dawes, P and Keagle, PJ and McDonough, JA and Boopathy, S and Sena-Esteves, M and Lutz, C and Skarnes, WC and Lim, ET and Schafer, DP and Massi, F and Landers, JE and Bosco, DA}, title = {Expression of ALS-PFN1 impairs vesicular degradation in iPSC-derived microglia.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2023.06.01.541136}, pmid = {37398081}, issn = {2692-8205}, abstract = {Microglia play a pivotal role in neurodegenerative disease pathogenesis, but the mechanisms underlying microglia dysfunction and toxicity remain to be fully elucidated. To investigate the effect of neurodegenerative disease-linked genes on the intrinsic properties of microglia, we studied microglia-like cells derived from human induced pluripotent stem cells (iPSCs), termed iMGs, harboring mutations in profilin-1 (PFN1) that are causative for amyotrophic lateral sclerosis (ALS). ALS-PFN1 iMGs exhibited lipid dysmetabolism and deficits in phagocytosis, a critical microglia function. Our cumulative data implicate an effect of ALS-linked PFN1 on the autophagy pathway, including enhanced binding of mutant PFN1 to the autophagy signaling molecule PI3P, as an underlying cause of defective phagocytosis in ALS-PFN1 iMGs. Indeed, phagocytic processing was restored in ALS-PFN1 iMGs with Rapamycin, an inducer of autophagic flux. These outcomes demonstrate the utility of iMGs for neurodegenerative disease research and highlight microglia vesicular degradation pathways as potential therapeutic targets for these disorders.}, } @article {pmid37397495, year = {2023}, author = {Boldin, R and Zychar, BC and Gonçalves, LRC and Sciani, JM}, title = {Design, in silico and pharmacological evaluation of a peptide inhibitor of BACE-1.}, journal = {Frontiers in pharmacology}, volume = {14}, number = {}, pages = {1184006}, pmid = {37397495}, issn = {1663-9812}, abstract = {Introduction: Alzheimer's disease (AD) is the main type of dementia, caused by the accumulation of amyloid plaques, formed by amyloid peptides after being processed from amyloid precursor protein (APP) by γ- and ß-secretases (BACE-1). Although amyloid peptides have been well established for AD, they have been found in other neurodegenerative diseases, such as Parkinson's disease, Lewy body dementia, and amyotrophic lateral sclerosis. Inhibitors of BACE-1 have been searched and developed, but clinical trials failed due to lack of efficacy or toxicity. Nevertheless, it is still considered a good therapeutic target, as it was proven to remove amyloid peptides and improve memory. Methods: In this work, we designed a peptide based on a sequence obtained from the marine fish Merluccius productus and evaluated it by molecular docking to verify its binding to BACE-1, which was tested experimentally by enzymatic kinetics and cell culture assays. The peptide was injected in healthy mice to study its pharmacokinetics and toxicity. Results: We could obtain a new sequence in which the first N-terminal amino acids and the last one bound to the catalytic site of BACE-1 and showed high stability and hydrophobicity. The synthetic peptide showed a competitive inhibition of BACE-1 and Ki = 94 nM, and when injected in differentiated neurons, it could reduce Aβ42o production. In plasma, its half-life is ∼1 h, clearance is 0.0015 μg/L/h, and Vss is 0.0015 μg/L/h. The peptide was found in the spleen and liver 30 min after injection and reduced its level after that, when it was quantified in the kidneys, indicating its fast distribution and urinary excretion. Interestingly, the peptide was found in the brain 2 h after its administration. Histological analysis showed no morphological alteration in any organ, as well as the absence of inflammatory cells, indicating a lack of toxicity. Discussion: We obtained a new BACE-1 inhibitor peptide with fast distribution to the tissues, without accumulation in any organ, but found in the brain, with the possibility to reach its molecular target, BACE-1, contributing to the reduction in the amyloid peptide, which causes amyloid-linked neurodegenerative diseases.}, } @article {pmid37396808, year = {2023}, author = {Vucic, S and Menon, P and Huynh, W and Mahoney, C and Ho, KS and Hartford, A and Rynders, A and Evan, J and Evan, J and Ligozio, S and Glanzman, R and Hotchkin, MT and Kiernan, MC}, title = {Efficacy and safety of CNM-Au8 in amyotrophic lateral sclerosis (RESCUE-ALS study): a phase 2, randomised, double-blind, placebo-controlled trial and open label extension.}, journal = {EClinicalMedicine}, volume = {60}, number = {}, pages = {102036}, pmid = {37396808}, issn = {2589-5370}, abstract = {BACKGROUND: CNM-Au8® is a catalytically-active gold nanocrystal neuroprotective agent that enhances intracellular energy metabolism and reduces oxidative stress. The phase 2, randomised, double-blind, placebo-controlled trial and open label extension RESCUE-ALS trial evaluated the efficacy and safety of CNM-Au8 for treatment of amyotrophic lateral sclerosis (ALS).

METHODS: RESCUE-ALS and its long-term open label extension (OLE) were conducted at two multidisciplinary ALS clinics located in Sydney, Australia: (i) the Brain and Mind Centre and (ii) Westmead Hospital. The double-blind portion of RESCUE-ALS was conducted from January 16, 2020 (baseline visit, first-patient first-visit (FPFV)) through July 13, 2021 (double-blind period, last-patient last-visit (LPLV)). Participants (N = 45) were randomised 1:1 to receive 30 mg of CNM-Au8 or matching placebo daily over 36 weeks in addition to background standard of care, riluzole. The primary outcome was mean percent change in summed motor unit number index (MUNIX), a sensitive neurophysiological biomarker of lower motor neuron function. Change in total (or summated) MUNIX score and change in forced vital capacity (FVC) were secondary outcome measures. ALS disease progression events, ALS Functional Rating Scale (ALSFRS-R) change, change in quality of life (ALSSQOL-SF) were assessed as exploratory outcome measures. Long-term survival evaluated vital status of original active versus placebo randomisation for all participants through at least 12 months following last-patient last-visit (LPLV) of the double-blind period. RESCUE-ALS and the open label study are registered in clinicaltrials.gov with registration numbers NCT04098406 and NCT05299658, respectively.

FINDINGS: In the intention-to-treat (ITT) population, there was no significant difference in the summated MUNIX score percent change (LS mean difference: 7.7%, 95% CI: -11.9 to 27.3%, p = 0.43), total MUNIX score change (18.8, 95% CI: -56.4 to 94.0), or FVC change (LS mean difference: 3.6, 95% CI: -12.4 to 19.7) between the active and placebo treated groups at week 36. In contrast, survival analyses through 12-month LPLV demonstrated a 60% reduction in all-cause mortality with CNM-Au8 treatment [hazard ratio = 0.408 (95% Wald CI: 0.166 to 1.001, log-rank p = 0.0429). 36 participants entered the open label extension (OLE), and those initially randomised to CNM-Au8 exhibited a slower rate of disease progression, as measured by time to the occurrence of death, tracheostomy, initiation of non-invasive ventilatory support, or gastrostomy tube placement. CNM-Au8 was well-tolerated, and no safety signals were observed.

INTERPRETATION: CNM-Au8, in combination with riluzole, was well-tolerated in ALS with no identified safety signals. While the primary and secondary outcomes of this trial were not significant, the clinically meaningful exploratory results support further investigation of CNM-Au8 in ALS.

FUNDING: The RESCUE-ALS was substantially funded by a grant from FightMND. Additional funding was provided by Clene Australia Pty Ltd.}, } @article {pmid37395323, year = {2023}, author = {Stevenson, R and Samokhina, E and Mangat, A and Rossetti, I and Purushotham, SS and Malladi, CS and Morley, JW and Buskila, Y}, title = {Astrocytic K[+] clearance during disease progression in amyotrophic lateral sclerosis.}, journal = {Glia}, volume = {71}, number = {10}, pages = {2456-2472}, doi = {10.1002/glia.24435}, pmid = {37395323}, issn = {1098-1136}, mesh = {Mice ; Animals ; *Amyotrophic Lateral Sclerosis ; Astrocytes ; Superoxide Dismutase-1 ; Motor Neurons/physiology ; Spinal Cord ; Disease Models, Animal ; Disease Progression ; Mice, Transgenic ; Superoxide Dismutase ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder in which patients lose motor functions due to progressive loss of motor neurons in the cortex, brainstem, and spinal cord. Whilst the loss of neurons is central to the disease, it is becoming clear that glia, specifically astrocytes, contribute to the onset and progression of neurodegeneration. Astrocytes play an important role in maintaining ion homeostasis in the extracellular milieu and regulate multiple brain functions by altering their extracellular concentrations. In this study, we have investigated the ability of astrocytes to maintain K[+] homeostasis in the brain via direct measurement of the astrocytic K[+] clearance rate in the motor and somatosensory cortices of an ALS mouse model (SOD1[G93A]). Using electrophysiological recordings from acute brain slices, we show region-specific alterations in the K[+] clearance rate, which was significantly reduced in the primary motor cortex but not the somatosensory cortex. This decrease was accompanied by significant changes in astrocytic morphology, impaired conductivity via Kir4.1 channels and low coupling ratio in astrocytic networks in the motor cortex, which affected their ability to form the K[+] gradient needed to disperse K[+] through the astrocytic syncytium. These findings indicate that the supportive function astrocytes typically provide to motoneurons is diminished during disease progression and provides a potential explanation for the increased vulnerability of motoneurons in ALS.}, } @article {pmid37395272, year = {2023}, author = {Hurtle, BT and Xie, L and Donnelly, CJ}, title = {Disrupting pathologic phase transitions in neurodegeneration.}, journal = {The Journal of clinical investigation}, volume = {133}, number = {13}, pages = {}, pmid = {37395272}, issn = {1558-8238}, support = {R01 NS127187/NS/NINDS NIH HHS/United States ; L30 AG048607/AG/NIA NIH HHS/United States ; R01 NS105756/NS/NINDS NIH HHS/United States ; }, mesh = {Humans ; Aged ; *TDP-43 Proteinopathies/pathology ; *Neurodegenerative Diseases/pathology ; *Frontotemporal Lobar Degeneration/metabolism/pathology ; *Amyotrophic Lateral Sclerosis/genetics/pathology ; Proteins ; }, abstract = {Solid-like protein deposits found in aged and diseased human brains have revealed a relationship between insoluble protein accumulations and the resulting deficits in neurologic function. Clinically diverse neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, frontotemporal lobar degeneration, and amyotrophic lateral sclerosis, exhibit unique and disease-specific biochemical protein signatures and abnormal protein depositions that often correlate with disease pathogenesis. Recent evidence indicates that many pathologic proteins assemble into liquid-like protein phases through the highly coordinated process of liquid-liquid phase separation. Over the last decade, biomolecular phase transitions have emerged as a fundamental mechanism of cellular organization. Liquid-like condensates organize functionally related biomolecules within the cell, and many neuropathology-associated proteins reside within these dynamic structures. Thus, examining biomolecular phase transitions enhances our understanding of the molecular mechanisms mediating toxicity across diverse neurodegenerative diseases. This Review explores the known mechanisms contributing to aberrant protein phase transitions in neurodegenerative diseases, focusing on tau and TDP-43 proteinopathies and outlining potential therapeutic strategies to regulate these pathologic events.}, } @article {pmid37394908, year = {2023}, author = {Bakavayev, S and Stavsky, A and Argueti-Ostrovsky, S and Yehezkel, G and Fridmann-Sirkis, Y and Barak, Z and Gitler, D and Israelson, A and Engel, S}, title = {Blocking an epitope of misfolded SOD1 ameliorates disease phenotype in a model of amyotrophic lateral sclerosis.}, journal = {Brain : a journal of neurology}, volume = {146}, number = {11}, pages = {4594-4607}, doi = {10.1093/brain/awad222}, pmid = {37394908}, issn = {1460-2156}, mesh = {Mice ; Animals ; Superoxide Dismutase-1/genetics ; *Amyotrophic Lateral Sclerosis/metabolism ; Superoxide Dismutase/genetics/metabolism ; Epitopes ; Phenotype ; Protein Folding ; Disease Models, Animal ; Mice, Transgenic ; }, abstract = {The current strategies to mitigate the toxicity of misfolded superoxide dismutase 1 (SOD1) in familial amyotrophic lateral sclerosis via blocking SOD1 expression in the CNS are indiscriminative for misfolded and intact proteins, and as such, entail a risk of depriving CNS cells of their essential antioxidant potential. As an alternative approach to neutralize misfolded and spare unaffected SOD1 species, we developed scFv-SE21 antibody that blocks the β6/β7 loop epitope exposed exclusively in misfolded SOD1. The β6/β7 loop epitope has previously been proposed to initiate amyloid-like aggregation of misfolded SOD1 and mediate its prion-like activity. The adeno-associated virus-mediated expression of scFv-SE21 in the CNS of hSOD1G37R mice rescued spinal motor neurons, reduced the accumulation of misfolded SOD1, decreased gliosis and thus delayed disease onset and extended survival by 90 days. The results provide evidence for the role of the exposed β6/β7 loop epitope in the mechanism of neurotoxic gain-of-function of misfolded SOD1 and open avenues for the development of mechanism-based anti-SOD1 therapeutics, whose selective targeting of misfolded SOD1 species may entail a reduced risk of collateral oxidative damage to the CNS.}, } @article {pmid37394881, year = {2023}, author = {Dilliott, AA and Kwon, S and Rouleau, GA and Iqbal, S and Farhan, SMK}, title = {Characterizing proteomic and transcriptomic features of missense variants in amyotrophic lateral sclerosis genes.}, journal = {Brain : a journal of neurology}, volume = {146}, number = {11}, pages = {4608-4621}, pmid = {37394881}, issn = {1460-2156}, support = {//CIHR/Canada ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics ; Transcriptome/genetics ; Proteomics ; Mutation, Missense/genetics ; Genetic Testing ; }, abstract = {Within recent years, there has been a growing number of genes associated with amyotrophic lateral sclerosis (ALS), resulting in an increasing number of novel variants, particularly missense variants, many of which are of unknown clinical significance. Here, we leverage the sequencing efforts of the ALS Knowledge Portal (3864 individuals with ALS and 7839 controls) and Project MinE ALS Sequencing Consortium (4366 individuals with ALS and 1832 controls) to perform proteomic and transcriptomic characterization of missense variants in 24 ALS-associated genes. The two sequencing datasets were interrogated for missense variants in the 24 genes, and variants were annotated with gnomAD minor allele frequencies, ClinVar pathogenicity classifications, protein sequence features including Uniprot functional site annotations, and PhosphoSitePlus post-translational modification site annotations, structural features from AlphaFold predicted monomeric 3D structures, and transcriptomic expression levels from Genotype-Tissue Expression. We then applied missense variant enrichment and gene-burden testing following binning of variation based on the selected proteomic and transcriptomic features to identify those most relevant to pathogenicity in ALS-associated genes. Using predicted human protein structures from AlphaFold, we determined that missense variants carried by individuals with ALS were significantly enriched in β-sheets and α-helices, as well as in core, buried or moderately buried regions. At the same time, we identified that hydrophobic amino acid residues, compositionally biased protein regions and regions of interest are predominantly enriched in missense variants carried by individuals with ALS. Assessment of expression level based on transcriptomics also revealed enrichment of variants of high and medium expression across all tissues and within the brain. We further explored enriched features of interest using burden analyses and identified individual genes were indeed driving certain enrichment signals. A case study is presented for SOD1 to demonstrate proof-of-concept of how enriched features may aid in defining variant pathogenicity. Our results present proteomic and transcriptomic features that are important indicators of missense variant pathogenicity in ALS and are distinct from features associated with neurodevelopmental disorders.}, } @article {pmid37394863, year = {2023}, author = {Zhao, YN and Fu, JY and He, J and Fan, DS}, title = {[Progress in the application of uric acid-lowering treatments in amyotrophic lateral sclerosis].}, journal = {Zhonghua nei ke za zhi}, volume = {62}, number = {7}, pages = {885-890}, doi = {10.3760/cma.j.cn112138-20220708-00498}, pmid = {37394863}, issn = {0578-1426}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy ; Uric Acid ; }, } @article {pmid37394036, year = {2023}, author = {Arnold, FJ and Nguyen, AD and Bedlack, RS and Bennett, CL and La Spada, AR}, title = {Intercellular transmission of pathogenic proteins in ALS: Exploring the pathogenic wave.}, journal = {Neurobiology of disease}, volume = {184}, number = {}, pages = {106218}, doi = {10.1016/j.nbd.2023.106218}, pmid = {37394036}, issn = {1095-953X}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism ; Superoxide Dismutase-1/metabolism ; Protein Aggregates ; C9orf72 Protein/genetics ; DNA-Binding Proteins/genetics/metabolism ; }, abstract = {In patients with amyotrophic lateral sclerosis (ALS), disease symptoms and pathology typically spread in a predictable spatiotemporal pattern beginning at a focal site of onset and progressing along defined neuroanatomical tracts. Like other neurodegenerative diseases, ALS is characterized by the presence of protein aggregates in postmortem patient tissue. Cytoplasmic, ubiquitin-positive aggregates of TDP-43 are observed in approximately 97% of sporadic and familial ALS patients, while SOD1 inclusions are likely specific to cases of SOD1-ALS. Additionally, the most common subtype of familial ALS, caused by a hexanucleotide repeat expansion in the first intron of the C9orf72 gene (C9-ALS), is further characterized by the presence of aggregated dipeptide repeat proteins (DPRs). As we will describe, cell-to-cell propagation of these pathological proteins tightly correlates with the contiguous spread of disease. While TDP-43 and SOD1 are capable of seeding protein misfolding and aggregation in a prion-like manner, C9orf72 DPRs appear to induce (and transmit) a 'disease state' more generally. Multiple mechanisms of intercellular transport have been described for all of these proteins, including anterograde and retrograde axonal transport, extracellular vesicle secretion, and macropinocytosis. In addition to neuron-to-neuron transmission, transmission of pathological proteins occurs between neurons and glia. Given that the spread of ALS disease pathology corresponds with the spread of symptoms in patients, the various mechanisms by which ALS-associated protein aggregates propagate through the central nervous system should be closely examined.}, } @article {pmid37393503, year = {2023}, author = {Vítor, J and Saracino, D and Ströer, S and Camuzat, A and Dorgham, K and Clot, F and Martin-Hardy, P and Pasquier, F and , and Le Ber, I}, title = {Atypical White Matter Hyperintensities Markedly Impact Plasma Neurofilament Light Chain Variability in GRN Patients.}, journal = {Journal of Alzheimer's disease : JAD}, volume = {94}, number = {4}, pages = {1351-1360}, doi = {10.3233/JAD-230315}, pmid = {37393503}, issn = {1875-8908}, mesh = {Humans ; Biomarkers ; *Frontotemporal Dementia/genetics ; Intermediate Filaments ; Mutation ; Neurofilament Proteins ; Progranulins/genetics ; *White Matter/diagnostic imaging ; }, abstract = {GRN mutations, causing frontotemporal dementia, can be associated with atypical white matter hyperintensities (WMH). We hypothesized that the presence of WMH may impact neurofilament light chain (NfL) levels, markers of neuroaxonal damage. We analyzed plasma NfL in 20 GRN patients and studied their association to visually-scored WMH burden. The 12 patients displaying atypical WMH had significantly higher NfL levels (98.4±34.9 pg/mL) than those without WMH (47.2±29.4 pg/mL, p = 0.003), independently from age, disease duration and Fazekas-Schmidt grade. NfL correlated with WMH burden (rho = 0.55, p = 0.01). This study prompts considering WMH burden as a variability factor when evaluating NfL levels in GRN patients.}, } @article {pmid37392160, year = {2023}, author = {Hivare, P and Mujmer, K and Swarup, G and Gupta, S and Bhatia, D}, title = {Endocytic pathways of pathogenic protein aggregates in neurodegenerative diseases.}, journal = {Traffic (Copenhagen, Denmark)}, volume = {24}, number = {10}, pages = {434-452}, doi = {10.1111/tra.12906}, pmid = {37392160}, issn = {1600-0854}, mesh = {Humans ; *Neurodegenerative Diseases/metabolism ; Protein Aggregates ; *Alzheimer Disease/metabolism ; *Parkinson Disease/metabolism ; alpha-Synuclein/metabolism ; }, abstract = {Endocytosis is the fundamental uptake process through which cells internalize extracellular materials and species. Neurodegenerative diseases (NDs) are characterized by a progressive accumulation of intrinsically disordered protein species, leading to neuronal death. Misfolding in many proteins leads to various NDs such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS) and other disorders. Despite the significance of disordered protein species in neurodegeneration, their spread between cells and the cellular uptake of extracellular species is not entirely understood. This review discusses the major internalization mechanisms of the different conformer species of these proteins and their endocytic mechanisms. We briefly introduce the broad types of endocytic mechanisms found in cells and then summarize what is known about the endocytosis of monomeric, oligomeric and aggregated conformations of tau, Aβ, α-Syn, Huntingtin, Prions, SOD1, TDP-43 and other proteins associated with neurodegeneration. We also highlight the key players involved in internalizing these disordered proteins and the several techniques and approaches to identify their endocytic mechanisms. Finally, we discuss the obstacles involved in studying the endocytosis of these protein species and the need to develop better techniques to elucidate the uptake mechanisms of a particular disordered protein species.}, } @article {pmid37391647, year = {2023}, author = {Karati, D and Mukherjee, S and Roy, S}, title = {Molecular and Structural Insight into Adenosine A2A Receptor in Neurodegenerative Disorders: A Significant Target for Efficient Treatment Approach.}, journal = {Molecular neurobiology}, volume = {60}, number = {10}, pages = {5987-6000}, pmid = {37391647}, issn = {1559-1182}, mesh = {Humans ; *Adenosine/pharmacology ; Receptor, Adenosine A2A/metabolism ; Ligands ; *Neurodegenerative Diseases/drug therapy ; Purinergic P1 Receptor Antagonists/therapeutic use ; Receptors, Purinergic P1 ; }, abstract = {All biological tissues and bodily fluids include the autacoid adenosine. The P1 class of purinergic receptors includes adenosine receptors. Four distinct G-protein-coupled receptors on the cellular membrane mediate the effects of adenosine, whose cytoplasmic content is regulated by producing/degrading enzymes and nucleoside transporters. A2A receptor has received a great deal of attention in recent years because it has a wide range of potential therapeutic uses. A2B and, more significantly, A2A receptors regulate numerous physiological mechanisms in the central nervous system (CNS). The inferior targetability of A2B receptors towards adenosine points that they might portray a promising medicinal target since they are triggered only under pharmacological circumstances (when adenosine levels rise up to micromolar concentrations). The accessibility of specific ligands for A2B receptors would permit the exploration of such a theory. A2A receptors mediate both potentially neurotoxic and neuroprotective actions. Hence, it is debatable to what extent they play a role in neurodegenerative illnesses. However, A2A receptor blockers have demonstrated clear antiparkinsonian consequences, and a significant attraction exists in the role of A2A receptors in other neurodegenerative disorders. Amyloid peptide extracellular accumulation and tau hyperphosphorylation are the pathogenic components of AD that lead to neuronal cell death, cognitive impairment, and memory loss. Interestingly, in vitro and in vivo research has shown that A2A adenosine receptor antagonists may block each of these clinical symptoms, offering a crucial new approach to combat a condition for which, regrettably, only symptomatic medications are currently available. At least two requirements must be met to determine whether such receptors are a target for diseases of the CNS: a complete understanding of the mechanisms governing A2A-dependent processes and the availability of ligands that can distinguish between the various receptor populations. This review concisely summarises the biological effects mediated by A2A adenosine receptors in neurodegenerative disorders and discusses the chemical characteristics of A2A adenosine receptor antagonists undergoing clinical trials. Selective A2A receptor blocker against neurodegenerative disorders.}, } @article {pmid37391243, year = {2023}, author = {Gerecht, RB and Nable, JV}, title = {Out-of-Hospital Cardiac Arrest.}, journal = {Emergency medicine clinics of North America}, volume = {41}, number = {3}, pages = {433-453}, doi = {10.1016/j.emc.2023.03.002}, pmid = {37391243}, issn = {1558-0539}, mesh = {Humans ; *Out-of-Hospital Cardiac Arrest/diagnosis/therapy ; *Emergency Medical Services ; }, abstract = {Survival from out-of-hospital cardiac arrest (OHCA) is predicated on a community and system-wide approach that includes rapid recognition of cardiac arrest, capable bystander CPR, effective basic and advanced life support (BLS and ALS) by EMS providers, and coordinated postresuscitation care. Management of these critically ill patients continues to evolve. This article focuses on the management of OHCA by EMS providers.}, } @article {pmid37390744, year = {2023}, author = {Eskandari, S and Rezayof, A and Asghari, SM and Hashemizadeh, S}, title = {Neurobiochemical characteristics of arginine-rich peptides explain their potential therapeutic efficacy in neurodegenerative diseases.}, journal = {Neuropeptides}, volume = {101}, number = {}, pages = {102356}, doi = {10.1016/j.npep.2023.102356}, pmid = {37390744}, issn = {1532-2785}, mesh = {Humans ; *Neurodegenerative Diseases/drug therapy ; Arginine ; Oxidative Stress ; Peptides/metabolism ; *Nucleic Acids/metabolism/therapeutic use ; *Alzheimer Disease/metabolism ; }, abstract = {Neurodegenerative diseases, including Alzheimer̕ s disease (AD), Parkinson̕ s disease (PD), Huntington̕ s disease (HD), and Amyotrophic Lateral Sclerosis (ALS) require special attention to find new potential treatment methods. This review aims to summarize the current knowledge of the relationship between the biochemical properties of arginine-rich peptides (ARPs) and their neuroprotective effects to deal with the harmful effects of risk factors. It seems that ARPs have portrayed a promising and fantastic landscape for treating neurodegeneration-associated disorders. With multimodal mechanisms of action, ARPs play various unprecedented roles, including as the novel delivery platforms for entering the central nervous system (CNS), the potent antagonists for calcium influx, the invader molecules for targeting mitochondria, and the protein stabilizers. Interestingly, these peptides inhibit the proteolytic enzymes and block protein aggregation to induce pro-survival signaling pathways. ARPs also serve as the scavengers of toxic molecules and the reducers of oxidative stress agents. They also have anti-inflammatory, antimicrobial, and anti-cancer properties. Moreover, by providing an efficient nucleic acid delivery system, ARPs can play an essential role in developing various fields, including gene vaccines, gene therapy, gene editing, and imaging. ARP agents and ARP/cargo therapeutics can be raised as an emergent class of neurotherapeutics for neurodegeneration. Part of the aim of this review is to present recent advances in treating neurodegenerative diseases using ARPs as an emerging and powerful therapeutic tool. The applications and progress of ARPs-based nucleic acid delivery systems have also been discussed to highlight their usefulness as a broad-acting class of drugs.}, } @article {pmid37390359, year = {2023}, author = {Sheers, NL and Howard, ME and Rochford, PD and Rautela, L and Chao, C and McKim, DA and Berlowitz, DJ}, title = {A Randomized Controlled Clinical Trial of Lung Volume Recruitment in Adults with Neuromuscular Disease.}, journal = {Annals of the American Thoracic Society}, volume = {20}, number = {10}, pages = {1445-1455}, pmid = {37390359}, issn = {2325-6621}, mesh = {Female ; Humans ; Adult ; Middle Aged ; Adolescent ; *Quality of Life ; Prospective Studies ; Lung Volume Measurements ; Lung ; *Neuromuscular Diseases/complications ; }, abstract = {Rationale: Clinical care guidelines advise that lung volume recruitment (LVR) be performed routinely by people with neuromuscular disease (NMD) to maintain lung and chest wall flexibility and slow lung function decline. However, the evidence base is limited, and no randomized controlled trials of regular LVR in adults have been published. Objectives: To evaluate the effect of regular LVR on respiratory function and quality of life in adults with NMD. Methods: A randomized controlled trial with assessor blinding was conducted between September 2015 and May 2019. People (>14 years old) with NMD and vital capacity <80% predicted were eligible, stratified by disease subgroup (amyotrophic lateral sclerosis/motor neuron disease or other NMDs), and randomized to 3 months of twice-daily LVR or breathing exercises. The primary outcome was change in maximum insufflation capacity (MIC) from baseline to 3 months, analyzed using a linear mixed model approach. Results: Seventy-six participants (47% woman; median age, 57 [31-68] years; mean baseline vital capacity, 40 ± 18% predicted) were randomized (LVR, n = 37). Seventy-three participants completed the study. There was a statistically significant difference in MIC between groups (linear model interaction effect P = 0.002, observed mean difference, 0.19 [0.00-0.39] L). MIC increased by 0.13 (0.01-0.25) L in the LVR group, predominantly within the first month. No interaction or treatment effects were observed in secondary outcomes of lung volumes, respiratory system compliance, and quality of life. No adverse events were reported. Conclusions: Regular LVR increased MIC in a sample of LVR-naive participants with NMD. We found no direct evidence that regular LVR modifies respiratory mechanics or slows the rate of lung volume decline. The implications of increasing MIC are unclear, and the change in MIC may represent practice. Prospective long-term clinical cohorts with comprehensive follow-up, objective LVR use, and clinically meaningful outcome data are needed. Clinical trial registered with anzctr.org.au (ACTRN12615000565549).}, } @article {pmid37388914, year = {2023}, author = {Kaivola, K and Chia, R and Ding, J and Rasheed, M and Fujita, M and Menon, V and Walton, RL and Collins, RL and Billingsley, K and Brand, H and Talkowski, M and Zhao, X and Dewan, R and Stark, A and Ray, A and Solaiman, S and Alvarez Jerez, P and Malik, L and Dawson, TM and Rosenthal, LS and Albert, MS and Pletnikova, O and Troncoso, JC and Masellis, M and Keith, J and Black, SE and Ferrucci, L and Resnick, SM and Tanaka, T and , and , and , and , and Topol, E and Torkamani, A and Tienari, P and Foroud, TM and Ghetti, B and Landers, JE and Ryten, M and Morris, HR and Hardy, JA and Mazzini, L and D'Alfonso, S and Moglia, C and Calvo, A and Serrano, GE and Beach, TG and Ferman, T and Graff-Radford, NR and Boeve, BF and Wszolek, ZK and Dickson, DW and Chiò, A and Bennett, DA and De Jager, PL and Ross, OA and Dalgard, CL and Gibbs, JR and Traynor, BJ and Scholz, SW}, title = {Genome-wide structural variant analysis identifies risk loci for non-Alzheimer's dementias.}, journal = {Cell genomics}, volume = {3}, number = {6}, pages = {100316}, pmid = {37388914}, issn = {2666-979X}, support = {P30 AG072975/AG/NIA NIH HHS/United States ; K08 AG065463/AG/NIA NIH HHS/United States ; U24 AG021886/AG/NIA NIH HHS/United States ; U01 AG061356/AG/NIA NIH HHS/United States ; P30 AG072980/AG/NIA NIH HHS/United States ; P30 AG010161/AG/NIA NIH HHS/United States ; P50 NS038377/NS/NINDS NIH HHS/United States ; P30 AG019610/AG/NIA NIH HHS/United States ; P30 AG066507/AG/NIA NIH HHS/United States ; R35 NS127253/NS/NINDS NIH HHS/United States ; T32 HG002295/HG/NHGRI NIH HHS/United States ; ZIA AG000935/ImNIH/Intramural NIH HHS/United States ; P30 AG066546/AG/NIA NIH HHS/United States ; RF1 AG057473/AG/NIA NIH HHS/United States ; ZIA NS003154/ImNIH/Intramural NIH HHS/United States ; U24 NS072026/NS/NINDS NIH HHS/United States ; }, abstract = {We characterized the role of structural variants, a largely unexplored type of genetic variation, in two non-Alzheimer's dementias, namely Lewy body dementia (LBD) and frontotemporal dementia (FTD)/amyotrophic lateral sclerosis (ALS). To do this, we applied an advanced structural variant calling pipeline (GATK-SV) to short-read whole-genome sequence data from 5,213 European-ancestry cases and 4,132 controls. We discovered, replicated, and validated a deletion in TPCN1 as a novel risk locus for LBD and detected the known structural variants at the C9orf72 and MAPT loci as associated with FTD/ALS. We also identified rare pathogenic structural variants in both LBD and FTD/ALS. Finally, we assembled a catalog of structural variants that can be mined for new insights into the pathogenesis of these understudied forms of dementia.}, } @article {pmid37388502, year = {2023}, author = {Mohamed, W and Kumar, J and Alghamdi, BS and Soliman, AH and Toshihide, Y}, title = {Neurodegeneration and inflammation crosstalk: Therapeutic targets and perspectives.}, journal = {IBRO neuroscience reports}, volume = {14}, number = {}, pages = {95-110}, pmid = {37388502}, issn = {2667-2421}, abstract = {Glia, which was formerly considered to exist just to connect neurons, now plays a key function in a wide range of physiological events, including formation of memory, learning, neuroplasticity, synaptic plasticity, energy consumption, and homeostasis of ions. Glial cells regulate the brain's immune responses and confers nutritional and structural aid to neurons, making them an important player in a broad range of neurological disorders. Alzheimer's, ALS, Parkinson's, frontotemporal dementia (FTD), and epilepsy are a few of the neurodegenerative diseases that have been linked to microglia and astroglia cells, in particular. Synapse growth is aided by glial cell activity, and this activity has an effect on neuronal signalling. Each glial malfunction in diverse neurodegenerative diseases is distinct, and we will discuss its significance in the progression of the illness, as well as its potential for future treatment.}, } @article {pmid37387467, year = {2023}, author = {Timmins, HC and Vucic, S and Kiernan, MC}, title = {Cortical hyperexcitability in amyotrophic lateral sclerosis: from pathogenesis to diagnosis.}, journal = {Current opinion in neurology}, volume = {36}, number = {4}, pages = {353-359}, doi = {10.1097/WCO.0000000000001162}, pmid = {37387467}, issn = {1473-6551}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/genetics/therapy ; Motor Neurons ; Transcranial Magnetic Stimulation/methods ; *Frontotemporal Dementia/diagnosis/genetics ; Biomarkers ; }, abstract = {PURPOSE OF REVIEW: Identification of upper motor neuron involvement remains a critical component of a diagnosis of amyotrophic lateral sclerosis (ALS), although supportive clinical signs are often not easily appreciated, particularly in the early symptomatic stages of the disease. Although diagnostic criteria have been developed to facilitate improved detection of lower motor neuron impairment through electrophysiological features that have improved diagnostic sensitivity, assessment of upper motor neuron involvement remains problematic.

RECENT FINDINGS: Recent evidence has emerged about pathophysiological processes, particularly glutamate-mediated excitotoxicity, which has resulted in the development of novel diagnostic investigations and uncovered potential therapeutic targets. Advances in genetics, including the C9orf72 gene, have changed concepts of ALS, from being classified as a neuromuscular disease to a disease that forms a continuum with other primary neurodegenerative disorders, particularly frontotemporal dementia. Transcranial magnetic stimulation has been utilized to provide pathophysiological insights, leading to the development of diagnostic and therapeutic biomarkers, which are now being introduced into the clinical setting.

SUMMARY: Specifically, the advent of cortical hyperexcitability has been consistently identified as an early and intrinsic feature of ALS. With greater accessibility of TMS techniques promoting clinical utilization, TMS measures of cortical function may develop as a diagnostic biomarker, with further potential utility in the clinical trial setting for monitoring of neuroprotective and genetic-based therapies.}, } @article {pmid37386798, year = {2023}, author = {Hirsch-Reinshagen, V and Hercher, C and Vila-Rodriguez, F and Neumann, M and Rademakers, R and Honer, WG and Hsiung, GR and Mackenzie, IR}, title = {Psychotic symptoms in frontotemporal dementia with TDP-43 tend to be associated with type B pathology.}, journal = {Neuropathology and applied neurobiology}, volume = {49}, number = {4}, pages = {e12921}, pmid = {37386798}, issn = {1365-2990}, support = {P01 AG019724/AG/NIA NIH HHS/United States ; U19 AG063911/AG/NIA NIH HHS/United States ; }, mesh = {Humans ; C9orf72 Protein/genetics ; DNA-Binding Proteins/genetics ; *Frontotemporal Dementia/genetics/pathology ; *Frontotemporal Lobar Degeneration/pathology ; *Psychotic Disorders/complications ; Retrospective Studies ; }, abstract = {AIMS: Psychotic symptoms are increasingly recognized as a distinguishing clinical feature in patients with dementia due to frontotemporal lobar degeneration with TDP-43 pathology (FTLD-TDP). Within this group, carriers of the C9orf72 repeat expansion are particularly prone to develop delusions and hallucinations.

METHODS: The present retrospective study sought to provide novel details about the relationship between FTLD-TDP pathology and the presence of psychotic symptoms during life.

RESULTS: We found that FTLD-TDP subtype B was more frequent in patients with psychotic symptoms than in those without. This relationship was present even when corrected for the presence of C9orf72 mutation, suggesting that pathophysiological processes leading to the development of subtype B pathology may increase the risk of psychotic symptoms. Within the group of FTLD-TDP cases with subtype B pathology, psychotic symptoms tended to be associated with a greater burden of TDP-43 pathology in the white matter and a lower burden in lower motor neurons. When present, pathological involvement of motor neurons was more likely to be asymptomatic in patients with psychosis.

CONCLUSIONS: This work suggests that psychotic symptoms in patients with FTLD-TDP tend to be associated with subtype B pathology. This relationship is not completely explained by the effects of the C9orf72 mutation and raises the possibility of a direct link between psychotic symptoms and this particular pattern of TDP-43 pathology.}, } @article {pmid37386297, year = {2023}, author = {Sheridan, C}, title = {Unprecedented blood biomarker enables ALS drug approval.}, journal = {Nature biotechnology}, volume = {41}, number = {7}, pages = {886-888}, doi = {10.1038/s41587-023-01862-0}, pmid = {37386297}, issn = {1546-1696}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/blood/diagnosis/drug therapy ; Biomarkers/blood ; Drug Approval ; }, } @article {pmid37386082, year = {2023}, author = {Szebényi, K and Barrio-Hernandez, I and Gibbons, GM and Biasetti, L and Troakes, C and Beltrao, P and Lakatos, A}, title = {A human proteogenomic-cellular framework identifies KIF5A as a modulator of astrocyte process integrity with relevance to ALS.}, journal = {Communications biology}, volume = {6}, number = {1}, pages = {678}, pmid = {37386082}, issn = {2399-3642}, support = {MR/P008658/1/MRC_/Medical Research Council/United Kingdom ; MR/X006867/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics ; Astrocytes ; Genome-Wide Association Study ; Kinesins/genetics ; *Proteogenomics ; }, abstract = {Genome-wide association studies identified several disease-causing mutations in neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). However, the contribution of genetic variants to pathway disturbances and their cell type-specific variations, especially in glia, is poorly understood. We integrated ALS GWAS-linked gene networks with human astrocyte-specific multi-omics datasets to elucidate pathognomonic signatures. It predicts that KIF5A, a motor protein kinesin-1 heavy-chain isoform, previously detected only in neurons, can also potentiate disease pathways in astrocytes. Using postmortem tissue and super-resolution structured illumination microscopy in cell-based perturbation platforms, we provide evidence that KIF5A is present in astrocyte processes and its deficiency disrupts structural integrity and mitochondrial transport. We show that this may underly cytoskeletal and trafficking changes in SOD1 ALS astrocytes characterised by low KIF5A levels, which can be rescued by c-Jun N-terminal Kinase-1 (JNK1), a kinesin transport regulator. Altogether, our pipeline reveals a mechanism controlling astrocyte process integrity, a pre-requisite for synapse maintenance and suggests a targetable loss-of-function in ALS.}, } @article {pmid37385457, year = {2023}, author = {DuMont, M and Agostinis, A and Singh, K and Swan, E and Buttle, Y and Tropea, D}, title = {Sex representation in neurodegenerative and psychiatric disorders' preclinical and clinical studies.}, journal = {Neurobiology of disease}, volume = {184}, number = {}, pages = {106214}, doi = {10.1016/j.nbd.2023.106214}, pmid = {37385457}, issn = {1095-953X}, mesh = {Humans ; Male ; Female ; *Alzheimer Disease ; *Parkinson Disease ; *Amyotrophic Lateral Sclerosis/epidemiology/therapy ; *Attention Deficit Disorder with Hyperactivity ; }, abstract = {Many studies show the importance of biological sex for the onset, progression, and response to treatment in brain disorders. In line with these reports, health agencies have requested that all trials, both at the clinical and preclinical level, use a similar number of male and female subjects to correctly interpret the results. Despite these guidelines, many studies still tend to be unbalanced in the use of male and female subjects. In this review we consider three neurodegenerative disorders: Alzheimer's disease, Parkinson's disease, Amyotrophic lateral sclerosis, and three psychiatric disorders: Depression, Attention Deficit Hyperactivity Disorder, and Schizophrenia. These disorders were chosen because of their prevalence and their recognized sex-specific differences in onset, progression, and response to treatment. Alzheimer's disease and Depression demonstrate higher prevalence in females, whereas Parkinson's Disease, Amyotrophic lateral sclerosis, Attention Deficit Hyperactivity Disorder, and schizophrenia show higher prevalence in males. Results from preclinical and clinical studies examining each of these disorders revealed sex-specific differences in risk factors, diagnostic biomarkers, and treatment response and efficacy, suggesting a role for sex-specific therapies in neurodegenerative and neuropsychiatric disorders. However, the qualitative analysis of the percentage of males and females enrolled in clinical trials in the last two decades shows that for most of the disorders, there is still a sex bias in the patients' enrolment.}, } @article {pmid37384409, year = {2023}, author = {Tejwani, L and Jung, Y and Kokubu, H and Sowmithra, S and Ni, L and Lee, C and Sanders, B and Lee, PJ and Xiang, Y and Luttik, K and Soriano, A and Yoon, J and Park, J and Ro, HH and Ju, H and Liao, C and Tieze, SM and Rigo, F and Jafar-Nejad, P and Lim, J}, title = {Reduction of nemo-like kinase increases lysosome biogenesis and ameliorates TDP-43-related neurodegeneration.}, journal = {The Journal of clinical investigation}, volume = {133}, number = {16}, pages = {}, pmid = {37384409}, issn = {1558-8238}, support = {R21 MH119803/MH/NIMH NIH HHS/United States ; R01 NS083706/NS/NINDS NIH HHS/United States ; R01 NS088321/NS/NINDS NIH HHS/United States ; R01 AG076154/AG/NIA NIH HHS/United States ; R01 AG066447/AG/NIA NIH HHS/United States ; R01 AG074609/AG/NIA NIH HHS/United States ; T32 NS007224/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Mice ; *Amyotrophic Lateral Sclerosis/metabolism ; DNA-Binding Proteins/genetics/metabolism ; Lysosomes/metabolism ; *Neurodegenerative Diseases/genetics ; Humans ; }, abstract = {Protein aggregation is a hallmark of many neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS). Although mutations in TARDBP, encoding transactive response DNA-binding protein 43 kDa (TDP-43), account for less than 1% of all ALS cases, TDP-43-positive aggregates are present in nearly all ALS patients, including patients with sporadic ALS (sALS) or carrying other familial ALS-causing (fALS-causing) mutations. Interestingly, TDP-43 inclusions are also present in subsets of patients with frontotemporal dementia, Alzheimer's disease, and Parkinson's disease; therefore, methods of activating intracellular protein quality control machinery capable of clearing toxic cytoplasmic TDP-43 species may alleviate disease-related phenotypes. Here, we identify a function of nemo-like kinase (Nlk) as a negative regulator of lysosome biogenesis. Genetic or pharmacological reduction of Nlk increased lysosome formation and improved clearance of aggregated TDP-43. Furthermore, Nlk reduction ameliorated pathological, behavioral, and life span deficits in 2 distinct mouse models of TDP-43 proteinopathy. Because many toxic proteins can be cleared through the autophagy/lysosome pathway, targeted reduction of Nlk represents a potential approach to therapy development for multiple neurodegenerative disorders.}, } @article {pmid37384248, year = {2023}, author = {Hipke, K and Pitter, B and Hruscha, A and van Bebber, F and Modic, M and Bansal, V and Lewandowski, SA and Orozco, D and Edbauer, D and Bonn, S and Haass, C and Pohl, U and Montanez, E and Schmid, B}, title = {Loss of TDP-43 causes ectopic endothelial sprouting and migration defects through increased fibronectin, vcam 1 and integrin α4/β1.}, journal = {Frontiers in cell and developmental biology}, volume = {11}, number = {}, pages = {1169962}, pmid = {37384248}, issn = {2296-634X}, abstract = {Aggregation of the Tar DNA-binding protein of 43 kDa (TDP-43) is a pathological hallmark of amyotrophic lateral sclerosis and frontotemporal dementia and likely contributes to disease by loss of nuclear function. Analysis of TDP-43 function in knockout zebrafish identified an endothelial directional migration and hypersprouting phenotype during development prior lethality. In human umbilical vein cells (HUVEC) the loss of TDP-43 leads to hyperbranching. We identified elevated expression of FIBRONECTIN 1 (FN1), the VASCULAR CELL ADHESION MOLECULE 1 (VCAM1), as well as their receptor INTEGRIN α4β1 (ITGA4B1) in HUVEC cells. Importantly, reducing the levels of ITGA4, FN1, and VCAM1 homologues in the TDP-43 loss-of-function zebrafish rescues the angiogenic defects indicating the conservation of human and zebrafish TDP-43 function during angiogenesis. Our study identifies a novel pathway regulated by TDP-43 important for angiogenesis during development.}, } @article {pmid37383106, year = {2023}, author = {Wu, C and Feng, Y}, title = {Exploring the potential of mindfulness-based therapy in the prevention and treatment of neurodegenerative diseases based on molecular mechanism studies.}, journal = {Frontiers in neuroscience}, volume = {17}, number = {}, pages = {1097067}, pmid = {37383106}, issn = {1662-4548}, abstract = {Neurodegenerative diseases (ND) have received increasing attention due to their irreversibility, but there is still no means to completely cure ND in clinical practice. Mindfulness therapy (MT), including Qigong, Tai Chi, meditation, and yoga, etc., has become an effective complementary treatment modality in solving clinical and subclinical problems due to its advantages of low side effects, less pain, and easy acceptance by patients. MT is primarily used to treat mental and emotional disorders. In recent years, evidence has shown that MT has a certain therapeutic effect on ND with a potential molecular basis. In this review, we summarize the pathogenesis and risk factors of Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS), relating to telomerase activity, epigenetics, stress, and the pro-inflammatory transcription factor nuclear factor kappa B (NF-κB) mediated inflammatory response, and analyze the molecular mechanism basis of MT to prevent and treat ND, to provide possible explanations for the potential of MT treatments for ND.}, } @article {pmid37382103, year = {2023}, author = {Benatar, M and Turner, MR and Wuu, J}, title = {Presymptomatic amyotrophic lateral sclerosis: from characterization to prevention.}, journal = {Current opinion in neurology}, volume = {36}, number = {4}, pages = {360-364}, pmid = {37382103}, issn = {1473-6551}, support = {R01 NS105479/NS/NINDS NIH HHS/United States ; TURNER/OCT18/989-797/MNDA_/Motor Neurone Disease Association/United Kingdom ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/genetics/prevention & control ; *Frontotemporal Dementia/genetics ; Longitudinal Studies ; Biomarkers ; Asymptomatic Diseases ; }, abstract = {PURPOSE OF REVIEW: Significant progress in characterizing presymptomatic amyotrophic lateral sclerosis (ALS) is ushering in an era of potential disease prevention. Although these advances have largely been based on cohorts of deep-phenotyped mutation carriers at an elevated risk for ALS, there are increasing opportunities to apply principles and insights gleaned, to the broader population at risk for ALS [and frontotemporal dementia (FTD)].

RECENT FINDINGS: The discovery that blood neurofilament light chain (NfL) level increases presymptomatically and may serve as a susceptibility biomarker, predicting timing of phenoconversion in some mutation carriers, has empowered the first-ever prevention trial in SOD1 -ALS. Moreover, there is emerging evidence that presymptomatic disease is not uniformly clinically silent, with mild motor impairment (MMI), mild cognitive impairment (MCI), and/or mild behavioral impairment (MBI) representing a prodromal stage of disease. Structural and functional brain abnormalities, as well as systemic markers of metabolic dysfunction, have emerged as potentially even earlier markers of presymptomatic disease. Ongoing longitudinal studies will determine the extent to which these reflect an endophenotype of genetic risk.

SUMMARY: The discovery of presymptomatic biomarkers and the delineation of prodromal states is yielding unprecedented opportunities for earlier diagnosis, treatment, and perhaps even prevention of genetic and apparently sporadic forms of disease.}, } @article {pmid37381832, year = {2023}, author = {Zhang, Y and Cao, X and Gao, Z and Ma, X and Wang, Q and Xu, X and Cai, X and Zhang, Y and Zhang, Z and Wei, G and Wen, B}, title = {MATR3-antisense LINE1 RNA meshwork scaffolds higher-order chromatin organization.}, journal = {EMBO reports}, volume = {24}, number = {8}, pages = {e57550}, pmid = {37381832}, issn = {1469-3178}, mesh = {Humans ; *RNA, Antisense ; Histones/genetics ; *Amyotrophic Lateral Sclerosis/genetics ; Chromatin/genetics ; Cell Nucleus/genetics/metabolism ; RNA-Binding Proteins/genetics ; Nuclear Matrix-Associated Proteins/genetics/metabolism ; }, abstract = {Long interspersed nuclear elements (LINEs) play essential roles in shaping chromatin states, while the factors that cooperate with LINEs and their roles in higher-order chromatin organization remain poorly understood. Here, we show that MATR3, a nuclear matrix protein, interplays with antisense LINE1 (AS L1) RNAs to form a meshwork via phase separation, providing a dynamic platform for chromatin spatial organization. MATR3 and AS L1 RNAs affect the nuclear localization of each other. After MATR3 depletion, the chromatin, particularly H3K27me3-modified chromatin, redistributes in the cell nuclei. Topologically associating domains (TADs) that highly transcribe MATR3-associated AS L1 RNAs show decreased intra-TAD interactions in both AML12 and ES cells. MATR3 depletion increases the accessibility of H3K27me3 domains adjacent to MATR3-associated AS L1, without affecting H3K27me3 modifications. Furthermore, amyotrophic lateral sclerosis (ALS)-associated MATR3 mutants alter biophysical features of the MATR3-AS L1 RNA meshwork and cause an abnormal H3K27me3 staining. Collectively, we reveal a role of the meshwork formed by MATR3 and AS L1 RNAs in gathering chromatin in the nucleus.}, } @article {pmid37380145, year = {2023}, author = {Mercadante, S and Al-Husinat, L}, title = {Palliative Care in Amyotrophic Lateral Sclerosis.}, journal = {Journal of pain and symptom management}, volume = {66}, number = {4}, pages = {e485-e499}, doi = {10.1016/j.jpainsymman.2023.06.029}, pmid = {37380145}, issn = {1873-6513}, mesh = {Humans ; Palliative Care ; *Amyotrophic Lateral Sclerosis/therapy/diagnosis ; Quality of Life ; *Neurodegenerative Diseases ; *Hospice and Palliative Care Nursing ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease of the motor neurons. Given the evolutive characteristics of this disease, palliative care principles should be a foundation of ALS care. A multidisciplinary medical intervention is of paramount importance in the different phases of disease. The involvement of the palliative care team improves quality of life and symptoms, and prognosis. Early initiation is of paramount importance to ensuring patient-centered care, when the patient has still the capability to communicate effectively and participate in his medical care. Advance care planning supports patients and family members in understanding and sharing their preferences according to their personal values and life goals regarding future medical treatment. The principal problems which require intensive supportive care include cognitive disturbances, psychological distress, pain, sialorrhrea, nutrition, and ventilatory support. Communication skills of health-care professionals are mandatory to manage the inevitability of death. Palliative sedation has peculiar aspects in this population, particularly with the decision of withdrawing ventilatory support.}, } @article {pmid37379901, year = {2023}, author = {Rypka, KJ and Goldfarb, N and Mansh, M}, title = {Response to the feasibility of Kreher et al's "Risk of melanoma and nonmelanoma skin cancer with immunosuppressants, part II: methotrexate, alkylating agents, biologics, and small molecule inhibitors".}, journal = {Journal of the American Academy of Dermatology}, volume = {89}, number = {4}, pages = {e181-e185}, doi = {10.1016/j.jaad.2023.05.095}, pmid = {37379901}, issn = {1097-6787}, mesh = {Humans ; Methotrexate/therapeutic use ; Immunosuppressive Agents ; *Biological Products ; Alkylating Agents ; Feasibility Studies ; *Skin Neoplasms/drug therapy/epidemiology ; *Melanoma/drug therapy ; }, } @article {pmid37379726, year = {2023}, author = {Floudiotis, N and Modi, G and Mochan, A}, title = {Motor neuron disease in black African patients at a tertiary care hospital in Soweto, South Africa.}, journal = {Journal of the neurological sciences}, volume = {451}, number = {}, pages = {120710}, doi = {10.1016/j.jns.2023.120710}, pmid = {37379726}, issn = {1878-5883}, mesh = {Female ; Humans ; Male ; *Amyotrophic Lateral Sclerosis/diagnosis ; Cross-Sectional Studies ; Delayed Diagnosis ; *Motor Neuron Disease ; South Africa/epidemiology ; Tertiary Care Centers ; Adult ; Middle Aged ; }, abstract = {INTRODUCTION: In this brief report, we describe the nature of ALS in a South African cohort of patients of Black African ancestry - a population which has been historically understudied.

METHODS: We performed a chart review of all patients attending the ALS/MND clinic at the Chris Hani Baragwanath Academic Hospital in Soweto, Johannesburg, South Africa, during the period 1 January 2015 to 30 June 2020. Cross-sectional demographic and clinical data captured at the time of diagnosis was collected.

RESULTS: Seventy-one patients were included in the study. Males constituted 66% (n = 47), with a male to female sex ratio of 2:1. The median age at onset of symptoms was 46 years (IQR 40-57) with a median disease duration at diagnosis (diagnostic delay) of 2 years (IQR 1-3). The onset was spinal in 76% and bulbar in 23%. The median ALSFRS-R score at time of presentation was 29 (IQR 23-38.5). The median ALSFRS-R slope (unit/month) was 0.80 (IQR 0.43-1.39). Sixty five patients (92%) were diagnosed with the classic ALS phenotype. Fourteen patients were known to be HIV positive, and of those, 12 were on antiretroviral treatment (ART). None of the patients had familial ALS.

CONCLUSION: Our findings of an earlier age at symptom onset and seemingly advanced disease at presentation in patients with Black African ancestry support the existing literature on the African population.}, } @article {pmid37379724, year = {2023}, author = {Paucar, M and Laffita-Mesa, J and Niemelä, V and Malmgren, H and Nennesmo, I and Lagerstedt-Robinson, K and Nordenskjöld, M and Svenningsson, P}, title = {Genetic screening for Huntington disease phenocopies in Sweden: A tertiary center case series focused on short tandem repeat (STR) disorders.}, journal = {Journal of the neurological sciences}, volume = {451}, number = {}, pages = {120707}, doi = {10.1016/j.jns.2023.120707}, pmid = {37379724}, issn = {1878-5883}, mesh = {*Huntington Disease/diagnosis/genetics ; Spinocerebellar Ataxias ; Sweden ; Humans ; C9orf72 Protein/genetics ; *Frontotemporal Dementia/genetics ; *Amyotrophic Lateral Sclerosis/genetics ; Genetic Testing ; *Prion Diseases ; Microsatellite Repeats ; Ubiquitin-Protein Ligases/genetics ; DNA Repeat Expansion ; *Prions ; }, abstract = {OBJECTIVE: To perform a screening for Huntington disease (HD) phenocopies in a Swedish cohort.

METHODS: Seventy-three DNA samples negative for HD were assessed at a tertiary center in Stockholm. The screening included analyses for C9orf72-frontotemporal dementia/amyotrophic lateral sclerosis (C9orf72-FTD/ALS), octapeptide repeat insertions (OPRIs) in PRNP associated with inherited prion diseases (IPD), Huntington's disease-like 2 (HDL2), spinocerebellar ataxia-2 (SCA2), spinocerebellar ataxia 3 (SCA3) and spinocerebellar ataxia-17 (SCA17). Targeted genetic analysis was carried out in two cases based on the salient phenotypic features.

RESULTS: The screening identified two patients with SCA17, one patient with IPD associated with 5-OPRI but none with nucleotide expansions in C9orf72 or for HDL2, SCA2 or SCA3. Furthermore, SGCE-myoclonic-dystonia 11 (SGCE-M-D) and benign hereditary chorea (BHC) was diagnosed in two sporadic cases. WES identified VUS in STUB1 in two patients with predominant cerebellar ataxia.

CONCLUSIONS: Our results are in keeping with previous screenings and suggest that other genes yet to be discovered are involved in the etiology of HD phenocopies.}, } @article {pmid37378756, year = {2023}, author = {Sassi, S and Bianchi, E and Diamanti, L and Tornabene, D and Sette, E and Medici, D and Matà, S and Leccese, D and Sperti, M and Martinelli, I and Ghezzi, A and Mandrioli, J and Iuzzolino, VV and Dubbioso, R and Trojsi, F and Passaniti, C and D'Alvano, G and Filosto, M and Padovani, A and Mazzini, L and De Marchi, F and Zinno, L and Nuredini, A and Bongioanni, P and Dolciotti, C and Canali, E and Toschi, G and Petrucci, A and Perna, A and Riso, V and Inghilleri, M and Libonati, L and Cambieri, C and Pupillo, E}, title = {Retrospective observational study on the use of acetyl-L-carnitine in ALS.}, journal = {Journal of neurology}, volume = {270}, number = {11}, pages = {5344-5357}, pmid = {37378756}, issn = {1432-1459}, mesh = {Humans ; *Acetylcarnitine/therapeutic use ; *Amyotrophic Lateral Sclerosis/diagnosis ; Retrospective Studies ; Case-Control Studies ; Double-Blind Method ; }, abstract = {ALCAR (Acetyl-L-carnitine) is a donor of acetyl groups and increases the intracellular levels of carnitine, the primary transporter of fatty acids across the mitochondrial membranes. In vivo studies showed that ALCAR decrease oxidative stress markers and pro-inflammatory cytokines. In a previous double-blind placebo-controlled phase II trial showed positive effects on self-sufficiency (defined as a score of 3+ on the ALSFRS-R items for swallowing, cutting food and handling utensils, and walking) ALSFRS-R total score and FVC. We conducted an observational, retrospective, multicentre, case-control study to provide additional data on the effects of ALCAR in subjects with ALS in Italy. Subjects treated with ALCAR 1.5 g/day or 3 g/day were included and matched with not treated subjects by sex, age at diagnosis, site of onset, and time from diagnosis to baseline, (45 subjects per group). ALCAR 3 g/day vs not treated: 22 not treated subjects (48.9%) were still alive at 24 months after baseline, compared to 23 (51.1%) treated subjects (adj. OR 1.18, 95% CI 0.46-3.02). No statistically significant differences were detected in ALSFRS nor FVC nor self-sufficiency. ALCAR 1.5 g/day vs not treated: 22 not treated subjects (48.9%) were still alive at 24 months after baseline, compared to 32 (71.1%) treated subjects (adj. OR 0.27, 95% CI 0.10-0.71). For ALSFRS-R, a mean slope of - 1.0 was observed in treated subjects compared to - 1.4 in those not treated (p = 0.0575). No statistically significant difference was detected in the FVC nor self-sufficiency. Additional evidence should be provided to confirm the efficacy of the drug and provide a rationale for the dosage.}, } @article {pmid37378058, year = {2023}, author = {Sancho, J and Ferrer, S}, title = {How to increase noninvasive ventilation effectiveness in bulbar amyotrophic lateral sclerosis patients.}, journal = {Breathe (Sheffield, England)}, volume = {19}, number = {1}, pages = {220266}, pmid = {37378058}, issn = {1810-6838}, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease in which the respiratory muscles are also affected, leading to respiratory failure. Bulbar impairment develops in almost all cases during the course of the disease, becoming severe in the late stages of disease. Noninvasive ventilation (NIV) has been shown to increase survival in ALS; however, severe bulbar dysfunction has a negative impact on NIV tolerance and effectiveness. Therefore, certain steps should be taken to improve NIV outcomes in these patients including optimal ventilatory parameters, adequate interface selection, effective respiratory secretion management and control of bulbar symptoms.}, } @article {pmid37375224, year = {2023}, author = {Zhang, Y and Huang, J and Yu, K and Cui, X}, title = {G-Quadruplexes Formation by the C9orf72 Nucleotide Repeat Expansion d(GGGGCC)n and Conformation Regulation by Fangchinoline.}, journal = {Molecules (Basel, Switzerland)}, volume = {28}, number = {12}, pages = {}, pmid = {37375224}, issn = {1420-3049}, support = {KLEEMA202201//Key Laboratory of Ecology and Environment in 458 Minority Areas (Minzu University of China), National Ethnic Affairs Commission/ ; }, mesh = {Humans ; *Frontotemporal Dementia ; *G-Quadruplexes ; C9orf72 Protein/genetics ; Nucleotides ; *Amyotrophic Lateral Sclerosis/genetics ; RNA/chemistry ; DNA/genetics ; }, abstract = {The G-quadruplex (GQ)-forming hexanucleotide repeat expansion (HRE) in the C9orf72 (C9) gene has been found to be the most common cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) (collectively, C9ALS/FTD), implying the great significance of modulating C9-HRE GQ structures in C9ALS/FTD therapeutic treatment strategies. In this study, we investigated the GQ structures formed by varied lengths of C9-HRE DNA sequences d(GGGGCC)4 (C9-24mer) and d(GGGGCC)8 (C9-48mer), and found that the C9-24mer forms anti-parallel GQ (AP-GQ) in the presence of potassium ions, while the long C9-48mer bearing eight guanine tracts forms unstacked tandem GQ consisting of two C9-24mer unimolecular AP-GQs. Moreover, the natural small molecule Fangchinoline was screened out in order to be able to stabilize and alter the C9-HRE DNA to parallel GQ topology. Further study of the interaction of Fangchinoline with the C9-HRE RNA GQ unit r(GGGGCC)4 (C9-RNA) revealed that it can also recognize and improve the thermal stability of C9-HRE RNA GQ. Finally, use of AutoDock simulation results indicated that Fangchinoline binds to the groove regions of the parallel C9-HRE GQs. These findings pave the way for further studies of GQ structures formed by pathologically related long C9-HRE sequences, and also provide a natural small-molecule ligand that modulates the structure and stability of C9-HRE GQ, both in DNA and RNA levels. Altogether, this work may contribute to therapeutic approaches of C9ALS/FTD which take the upstream C9-HRE DNA region, as well as the toxic C9-HRE RNA, as targets.}, } @article {pmid37375216, year = {2023}, author = {De Luca, M and Ioele, G and Grande, F and Occhiuzzi, MA and Chieffallo, M and Garofalo, A and Ragno, G}, title = {Multivariate Curve Resolution Methodology Applied to the ATR-FTIR Data for Adulteration Assessment of Virgin Coconut Oil.}, journal = {Molecules (Basel, Switzerland)}, volume = {28}, number = {12}, pages = {}, pmid = {37375216}, issn = {1420-3049}, support = {PON R&I 2014-2020 - ARS01_00568//PON R&I 2014-2020 - ARS01_00568 - SI.F.I.PA.CRO.DE. - Sviluppo e industrializzazione farmaci innovativi per terapia molecolare personalizzata PA.CRO.DE/ ; }, mesh = {Coconut Oil ; Spectroscopy, Fourier Transform Infrared/methods ; Fourier Analysis ; *Food Contamination/analysis ; *Plant Oils/analysis ; Least-Squares Analysis ; Olive Oil/analysis ; }, abstract = {Virgin coconut oil (VCO) is a functional food with important health benefits. Its economic interest encourages fraudsters to deliberately adulterate VCO with cheap and low-quality vegetable oils for financial gain, causing health and safety problems for consumers. In this context, there is an urgent need for rapid, accurate, and precise analytical techniques to detect VCO adulteration. In this study, the use of Fourier transform infrared (FTIR) spectroscopy combined with multivariate curve resolution-alternating least squares (MCR-ALS) methodology was evaluated to verify the purity or adulteration of VCO with reference to low-cost commercial oils such as sunflower (SO), maize (MO) and peanut (PO) oils. A two-step analytical procedure was developed, where an initial control chart approach was designed to assess the purity of oil samples using the MCR-ALS score values calculated on a data set of pure and adulterated oils. The pre-treatment of the spectral data by derivatization with the Savitzky-Golay algorithm allowed to obtain the classification limits able to distinguish the pure samples with 100% of correct classifications in the external validation. In the next step, three calibration models were developed using MCR-ALS with correlation constraints for analysis of adulterated coconut oil samples in order to assess the blend composition. Different data pre-treatment strategies were tested to best extract the information contained in the sample fingerprints. The best results were achieved by derivative and standard normal variate procedures obtaining RMSEP and RE% values in the ranges of 1.79-2.66 and 6.48-8.35%, respectively. The models were optimized using a genetic algorithm (GA) to select the most important variables and the final models in the external validations gave satisfactory results in quantifying adulterants, with absolute errors and RMSEP of less than 4.6% and 1.470, respectively.}, } @article {pmid37375110, year = {2023}, author = {Xu, E and Park, S and Calderon, J and Cao, D and Liang, B}, title = {In Silico Identification and In Vitro Validation of Repurposed Compounds Targeting the RSV Polymerase.}, journal = {Microorganisms}, volume = {11}, number = {6}, pages = {}, pmid = {37375110}, issn = {2076-2607}, support = {R01 GM130950/GM/NIGMS NIH HHS/United States ; R01GM130950/NH/NIH HHS/United States ; }, abstract = {Respiratory Syncytial Virus (RSV) is the top cause of infant hospitalization globally, with no effective treatments available. Researchers have sought small molecules to target the RNA-dependent RNA Polymerase (RdRP) of RSV, which is essential for replication and transcription. Based on the cryo-EM structure of the RSV polymerase, in silico computational analysis including molecular docking and the protein-ligand simulation of a database, including 6554 molecules, is currently undergoing phases 1-4 of clinical trials and has resulted in the top ten repurposed compound candidates against the RSV polymerase, including Micafungin, Totrombopag, and Verubecestat. We performed the same procedure to evaluate 18 small molecules from previous studies and chose the top four compounds for comparison. Among the top identified repurposed compounds, Micafungin, an antifungal medication, showed significant inhibition and binding affinity improvements over current inhibitors such as ALS-8112 and Ribavirin. We also validated Micafungin's inhibition of the RSV RdRP using an in vitro transcription assay. These findings contribute to RSV drug development and hold promise for broad-spectrum antivirals targeting the non-segmented negative-sense (NNS) RNA viral polymerases, including those of rabies (RABV) and Ebola (EBOV).}, } @article {pmid37374084, year = {2023}, author = {McCluskey, G and Morrison, KE and Donaghy, C and McConville, J and McCarron, MO and McVerry, F and Duddy, W and Duguez, S}, title = {Serum Neurofilaments in Motor Neuron Disease and Their Utility in Differentiating ALS, PMA and PLS.}, journal = {Life (Basel, Switzerland)}, volume = {13}, number = {6}, pages = {}, pmid = {37374084}, issn = {2075-1729}, support = {Clinical research fellowship//Guarantors of Brain/ ; Clinical Research Fellowship//Association of British Neurologists/ ; Research Grant//Irish Institute of Clinical Neuroscience/ ; }, abstract = {Neurofilament levels are elevated in many neurodegenerative diseases and have shown promise as diagnostic and prognostic biomarkers in Amyotrophic Lateral Sclerosis (ALS), the most common form of Motor Neuron Disease (MND). This study assesses serum neurofilament light (NFL) and neurofilament heavy (NFH) chain concentrations in patients with ALS, other variants of motor neuron disease such as Progressive Muscular Atrophy (PMA) and Primary Lateral Sclerosis (PLS), and a range of other neurological diseases. It aims to evaluate the use of NFL and NFH to differentiate these conditions and for the prognosis of MND disease progression. NFL and NFH levels were quantified using electrochemiluminescence immunoassays (ECLIA). Both were elevated in 47 patients with MND compared to 34 patients with other neurological diseases and 33 healthy controls. NFL was able to differentiate patients with MND from the other groups with a Receiver Operating Characteristic (ROC) curve area under the curve (AUC) of 0.90 (p < 0.001). NFL correlated with the rate of disease progression in MND (rho 0.758, p < 0.001) and with the ALS Functional Rating Scale (rho -0.335, p = 0.021). NFL levels were higher in patients with ALS compared to both PMA (p = 0.032) and PLS (p = 0.012) and were able to distinguish ALS from both PMA and PLS with a ROC curve AUC of 0.767 (p = 0.005). These findings support the use of serum NFL to help diagnose and differentiate types of MND, in addition to providing prognostic information to patients and their families.}, } @article {pmid37373667, year = {2023}, author = {Sipilä, JOT}, title = {Adult-Onset Neuroepidemiology in Finland: Lessons to Learn and Work to Do.}, journal = {Journal of clinical medicine}, volume = {12}, number = {12}, pages = {}, pmid = {37373667}, issn = {2077-0383}, abstract = {Finland is a relatively small genetic isolate with a genetically non-homogenous population. Available Finnish data on neuroepidemiology of adult-onset disorders are limited, and this paper describes the conclusions that can be drawn and their implications. Apparently, Finnish people have a (relatively) high risk of developing Unverricht-Lundborg disease (EPM1), Multiple Sclerosis (MS), Amyotrophic Lateral Sclerosis (ALS), Spinal muscular atrophy, Jokela type (SMAJ) and adult-onset dystonia. On the other hand, some disorders, such as Friedreich's ataxia (FRDA) and Wilson's disease (WD), are almost absent or completely absent in the population. Valid and timely data concerning even many common disorders, such as stroke, migraine, neuropathy, Alzheimer's disease and Parkinson's disease, are unavailable, and there are virtually no data on many less-common neurological disorders, such as neurosarcoidosis or autoimmune encephalitides. There also appear to be marked regional differences in the incidence and prevalence of many diseases, suggesting that non-granular nationwide data may be misleading in many cases. Concentrated efforts to advance neuroepidemiological research in the country would be of clinical, administrative and scientific benefit, but currently, all progress is blocked by administrative and financial obstacles.}, } @article {pmid37371694, year = {2023}, author = {De Marchi, F and Franjkic, T and Schito, P and Russo, T and Nimac, J and Chami, AA and Mele, A and Vidatic, L and Kriz, J and Julien, JP and Apic, G and Russell, RB and Rogelj, B and Cannon, JR and Baralle, M and Agosta, F and Hecimovic, S and Mazzini, L and Buratti, E and Munitic, I}, title = {Emerging Trends in the Field of Inflammation and Proteinopathy in ALS/FTD Spectrum Disorder.}, journal = {Biomedicines}, volume = {11}, number = {6}, pages = {}, pmid = {37371694}, issn = {2227-9059}, abstract = {Proteinopathy and neuroinflammation are two main hallmarks of neurodegenerative diseases. They also represent rare common events in an exceptionally broad landscape of genetic, environmental, neuropathologic, and clinical heterogeneity present in patients. Here, we aim to recount the emerging trends in amyotrophic lateral sclerosis (ALS) and frontotemporal degeneration (FTD) spectrum disorder. Our review will predominantly focus on neuroinflammation and systemic immune imbalance in ALS and FTD, which have recently been highlighted as novel therapeutic targets. A common mechanism of most ALS and ~50% of FTD patients is dysregulation of TAR DNA-binding protein 43 (TDP-43), an RNA/DNA-binding protein, which becomes depleted from the nucleus and forms cytoplasmic aggregates in neurons and glia. This, in turn, via both gain and loss of function events, alters a variety of TDP-43-mediated cellular events. Experimental attempts to target TDP-43 aggregates or manipulate crosstalk in the context of inflammation will be discussed. Targeting inflammation, and the immune system in general, is of particular interest because of the high plasticity of immune cells compared to neurons.}, } @article {pmid37371389, year = {2023}, author = {Górska, A and Markiewicz-Gospodarek, A and Markiewicz, R and Chilimoniuk, Z and Borowski, B and Trubalski, M and Czarnek, K}, title = {Distribution of Iron, Copper, Zinc and Cadmium in Glia, Their Influence on Glial Cells and Relationship with Neurodegenerative Diseases.}, journal = {Brain sciences}, volume = {13}, number = {6}, pages = {}, pmid = {37371389}, issn = {2076-3425}, abstract = {Recent data on the distribution and influence of copper, zinc and cadmium in glial cells are summarized. This review also examines the relationship between those metals and their role in neurodegenerative diseases like Alzheimer disease, multiple sclerosis, Parkinson disease and Amyotrophic lateral sclerosis, which have become a great challenge for today's physicians. The studies suggest that among glial cells, iron has the highest concentration in oligodendrocytes, copper in astrocytes and zinc in the glia of hippocampus and cortex. Previous studies have shown neurotoxic effects of copper, iron and manganese, while zinc can have a bidirectional effect, i.e., neurotoxic but also neuroprotective effects depending on the dose and disease state. Recent data point to the association of metals with neurodegeneration through their role in the modulation of protein aggregation. Metals can accumulate in the brain with aging and may be associated with age-related diseases.}, } @article {pmid37369876, year = {2023}, author = {Verde, F and Milone, I and Colombo, E and Maranzano, A and Dubini, A and Colombrita, C and Gentile, F and Doretti, A and Torre, S and Messina, S and Morelli, C and Torresani, E and Poletti, B and Priori, A and Maderna, L and Ratti, A and Silani, V and Ticozzi, N}, title = {Phosphorylated tau in plasma could be a biomarker of lower motor neuron impairment in amyotrophic lateral sclerosis.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {44}, number = {10}, pages = {3697-3702}, pmid = {37369876}, issn = {1590-3478}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis ; Motor Neurons ; Biomarkers/cerebrospinal fluid ; tau Proteins/cerebrospinal fluid ; }, abstract = {INTRODUCTION: Plasma levels of phosphorylated tau (P-tau181) have been recently reported to be increased in amyotrophic lateral sclerosis (ALS) and associated with lower motor neuron (LMN) impairment.

PATIENTS AND METHODS: We quantified plasma P-tau181 (pP-tau181) in a cohort of 29 deeply phenotyped ALS patients using the new fully automated Lumipulse assay and analysed phenotype-biomarker correlations.

RESULTS: pP-tau181 levels correlated positively with a clinical LMN score (r = 0.3803) and negatively, albeit not significantly, with a composite index of muscle strength (r =  - 0.3416; p = 0.0811), but not with Penn Upper Motor Neuron (UMN) Score. Accordingly, pP-tau181 correlated with electromyographic indices of spinal active and chronic denervation (r = 0.4507 and r = 0.3864, respectively) but not with transcranial magnetic stimulation parameters of UMN dysfunction. pP-tau181 levels did not correlate with those in the cerebrospinal fluid (CSF), serum NFL, serum GFAP, CSF/serum albumin ratio, or estimated glomerular filtration rate, but correlated with plasma creatine kinase levels (r = 0.4661). Finally, while not being associated with neuropsychological phenotype, pP-tau181 correlated negatively with pH (r =  - 0.5632) and positively with partial pressure of carbon dioxide (PaCO2; r = 0.7092), bicarbonate (sHCO3[-]; r = 0.6667) and base excess (r = 0.6611) on arterial blood gas analysis.

DISCUSSION: pP-tau181 has potential as ALS biomarker and could be associated with LMN impairment. Its raised levels might reflect pathophysiological processes (tau hyperphosphorylation and/or release) occurring in the axons of LMNs distantly from the CNS and the CSF. pP-tau181 could also be associated with respiratory dysfunction.}, } @article {pmid37369861, year = {2023}, author = {Zhu, Q and Xu, D and Huang, H and Li, D and Yang, D and Zhou, J and Zhao, Y}, title = {The safety and effectiveness of high-calorie therapy for treating amyotrophic lateral sclerosis: a systematic review and meta-analysis.}, journal = {Journal of neurology}, volume = {270}, number = {10}, pages = {4729-4743}, pmid = {37369861}, issn = {1432-1459}, support = {2022BCA055//Department of Science and Technology, Hubei Provincial People's Government/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy ; Lipids/therapeutic use ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder affecting the upper and lower motor neurons, which can lead to death from respiratory failure within 3-5 years after the onset of this disease. Nowadays, no drug can effectively slow down the progression of this disease. High-calorie therapy, an emerging complementary alternative treatment, has been reported in studies to prolong the survival time of patients, prevent muscle atrophy and provide a better prognosis. However, no systematic review and meta-analysis were performed to summarize the evidence of this therapy. This meta-analysis comprehensively evaluates the effectiveness and safety of high-calorie therapy for treating ALS.

METHODS: We searched the electronic databases from inception to 1 April 2023: PubMed, Embase, Web of Science, Cochrane Library, Scopus, Ovid/Medline, and ProQuest. Randomized controlled trials (RCTs) that met the inclusion criteria were performed by meta-analysis. All statistical analyses were performed in STATA software.

RESULTS: A total of six eligible RCTs were included in this meta-analysis, involving 370 ALS patients. The meta-analyses showed that high-calorie therapy had superiority in improving body weight (SMD = 1, 95% CI 0.36, 1.65) and BMI (SMD = 0.83, 95% CI 0.02, 1.63). With respect to safety, there was no difference between the high-calorie therapy and the control group regarding the number of adverse events (RR = 3.61, 95% CI 0.08, 162.49). However, ALSFRS-R scores (SMD = 0.34, 95% CI - 0.4, 1.08), survival rate (RR = 1.23, 95% CI 0.98, 1.55), and lipid profile (LDL: SMD = 0.21, 95% CI - 0.33, 0.75; HDL: SMD = 0.17, 95% CI - 0.37, 0.71; TC: SMD = 0.21, 95% CI - 0.33, 0.75), CRP (SMD = 0.85, 95% CI - 1.37, 3.06) showed no significant difference compared to the control groups.

CONCLUSIONS: High-calorie therapy is effective in gaining weight and BMI with few side effects. However, no significant superiority was detected in ALSFRS-R scores, survival time, lipid profile, and CRP indicator. The overall quality of the included studies is high, and the results have some credibility, but future corroboration by high-quality RCTs is also expected.}, } @article {pmid37368631, year = {2023}, author = {Barney, RE and Huang, G and Gallagher, TL and Tischbein, M and DeWitt, J and Martindale, R and LaRochelle, EMP and Tsongalis, GJ and Stommel, EW}, title = {Validation of a Droplet Digital PCR (ddPCR) Assay to Detect Cyanobacterial 16S rDNA in Human Lung Tissue.}, journal = {Toxics}, volume = {11}, number = {6}, pages = {}, pmid = {37368631}, issn = {2305-6304}, abstract = {Cyanobacteria produce a variety of secondary metabolites, including toxins that may contribute to the development of disease. Previous work was able to detect the presence of a cyanobacterial marker in human nasal and broncoalveolar lavage samples; however, it was not able to determine the quantification of the marker. To further research the relationship between cyanobacteria and human health, we validated a droplet digital polymerase chain reaction (ddPCR) assay to simultaneously detect the cyanobacterial 16S marker and a human housekeeping gene in human lung tissue samples. The ability to detect cyanobacteria in human samples will allow further research into the role cyanobacteria plays in human health and disease.}, } @article {pmid37368071, year = {2023}, author = {Xia, X and Zhang, W and Guo, J and Chang, X and Zhao, R and Wang, J and Pang, X and Zhang, J}, title = {Diagnostic utility of different dysphagia screening tools to detect dysphagia in individuals with amyotrophic lateral sclerosis.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {44}, number = {11}, pages = {3919-3927}, pmid = {37368071}, issn = {1590-3478}, abstract = {OBJECTIVE: Dysphagia is a common and serious clinical symptom of amyotrophic lateral sclerosis (ALS). The study aimed to evaluate the diagnostic utility of four dysphagia screening tools in ALS, including the ALS Functional Rating Scale-Revised (ALSFRS-R) bulbar subscale, water-swallowing test (WST), Eating Assessment Tool-10 (EAT-10) and Sydney Swallow Questionnaire (SSQ).

METHODS: A total of 68 individuals from First Hospital, Shanxi medical university, were recruited in the study. The ALSFRS-R, WST, EAT-10, SSQ and the gold standard video fluoroscopic swallowing study (VFSS) were performed. The Penetration Aspiration Scale (PAS) during VFSS was assessed to identify unsafe swallowing (PAS ≥ 3) and aspiration (PAS ≥ 6). Receiver operator characteristic curve (ROC) analyses were performed to evaluate the accuracy of the 4 tools. Youden index was used to determine the ideal cut-off value for each tool.

RESULTS: Of the patients, 20.59% (14/68) presented unsafety swallowing and 16.18% (11/68) had aspiration. The four tools could effectively identify patients with unsafe swallowing and aspiration. The EAT-10 had the maximum AUC (0.873 and 0.963, respectively) among the tools in the diagnosis of unsafe swallowing and aspiration. To detect unsafe swallowing and aspiration, an EAT-10 score of 6 (sensitivity: 78.6%, specificity: 87.0%) and an EAT-10 score of 8 (sensitivity: 90.9%, specificity: 91.2%), were the most appropriate cut-off points, respectively.

CONCLUSIONS: The ALSFRS-R bulbar subscale, WST, EAT-10, and SSQ could effectively identify unsafe swallowing and aspiration in patients with ALS. Of the four tools, the EAT-10 was relatively accurate, safe, and convenient. Further studies including more patients should be conducted to verify the conclusions.}, } @article {pmid37367854, year = {2023}, author = {Barros, ANAB and Felipe, MLDN and Barbosa, IR and Leite-Lais, L and Pedrosa, LFC}, title = {Dietary Intake of Micronutrients and Disease Severity in Patients with Amyotrophic Lateral Sclerosis.}, journal = {Metabolites}, volume = {13}, number = {6}, pages = {}, pmid = {37367854}, issn = {2218-1989}, support = {001//Coordenação de Aperfeicoamento de Pessoal de Nível Superior/ ; }, abstract = {Vitamins and essential metals have been studied as potential risk and prognostic factors in amyotrophic lateral sclerosis (ALS). This study aimed to evaluate the prevalence of inadequate micronutrient intake in ALS patients, comparing subgroups according to the disease severity. Data were obtained from the medical records of 69 individuals. Assessment of disease severity was determined by the revised ALS Functional Scale (ALSFRS-R), using the median as the cutoff. The prevalence of inadequate micronutrient intake was estimated using the Estimated Average Requirements (EAR) cut-point method. The prevalence of inadequate vitamin D, E, riboflavin, pyridoxine, folate, cobalamin, calcium, zinc, and magnesium intake was considered severe. Patients with lower ALSFRS-R scores had lower intakes of vitamin E (p < 0.001), niacin (p = 0.033), pantothenic acid (p = 0.037), pyridoxin (p = 0.008), folate (p = 0.009) and selenium (p = 0.001). Therefore, ALS patients should be monitored regarding dietary intake of micronutrients essential in neurological processes.}, } @article {pmid37366506, year = {2022}, author = {Erustes, AG and Guarache, GC and Guedes, EDC and Leão, AHFF and Pereira, GJDS and Smaili, SS}, title = {α-Synuclein Interactions in Mitochondria-ER Contacts: A Possible Role in Parkinson's Disease.}, journal = {Contact (Thousand Oaks (Ventura County, Calif.))}, volume = {5}, number = {}, pages = {25152564221119347}, pmid = {37366506}, issn = {2515-2564}, abstract = {Endoplasmic reticulum-mitochondria contact sites regulate various biological processes, such as mitochondrial dynamics, calcium homeostasis, autophagy and lipid metabolism. Notably, dysfunctions in these contact sites are closely related to neurodegenerative diseases, including Parkinson's disease, Alzheimer's disease and amyotrophic lateral sclerosis. However, details about the role of endoplasmic reticulum-mitochondria contact sites in neurodegenerative diseases remain unknown. In Parkinson's disease, interactions between α-synuclein in the contact sites and components of tether complexes that connect organelles can lead to various dysfunctions, especially with regards to calcium homeostasis. This review will summarize the main tether complexes present in endoplasmic reticulum-mitochondria contact sites, and their roles in calcium homeostasis and trafficking. We will discuss the impact of α-synuclein accumulation, its interaction with tethering complex components and the implications in Parkinson's disease pathology.}, } @article {pmid37365312, year = {2023}, author = {Li, Y and Dou, X and Liu, J and Xiao, Y and Zhang, Z and Hayes, L and Wu, R and Fu, X and Ye, Y and Yang, B and Ostrow, LW and He, C and Sun, S}, title = {Globally reduced N[6]-methyladenosine (m[6]A) in C9ORF72-ALS/FTD dysregulates RNA metabolism and contributes to neurodegeneration.}, journal = {Nature neuroscience}, volume = {26}, number = {8}, pages = {1328-1338}, pmid = {37365312}, issn = {1546-1726}, support = {RM1 HG008935/HG/NHGRI NIH HHS/United States ; R21 AG072078/AG/NIA NIH HHS/United States ; R01 NS123538/NS/NINDS NIH HHS/United States ; R01 NS107347/NS/NINDS NIH HHS/United States ; R01 ES030546/ES/NIEHS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; RF1 NS127925/NS/NINDS NIH HHS/United States ; K08 NS104273/NS/NINDS NIH HHS/United States ; RF1 NS113820/NS/NINDS NIH HHS/United States ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/metabolism ; C9orf72 Protein/genetics/metabolism ; Dipeptides/genetics/metabolism ; DNA Repeat Expansion/genetics ; *Frontotemporal Dementia/genetics/metabolism ; RNA ; RNA, Messenger ; }, abstract = {Repeat expansion in C9ORF72 is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Here we show that N[6]-methyladenosine (m[6]A), the most prevalent internal mRNA modification, is downregulated in C9ORF72-ALS/FTD patient-derived induced pluripotent stem cell (iPSC)-differentiated neurons and postmortem brain tissues. The global m[6]A hypomethylation leads to transcriptome-wide mRNA stabilization and upregulated gene expression, particularly for genes involved in synaptic activity and neuronal function. Moreover, the m[6]A modification in the C9ORF72 intron sequence upstream of the expanded repeats enhances RNA decay via the nuclear reader YTHDC1, and the antisense RNA repeats can also be regulated through m[6]A modification. The m[6]A reduction increases the accumulation of repeat RNAs and the encoded poly-dipeptides, contributing to disease pathogenesis. We further demonstrate that, by elevating m[6]A methylation, we could significantly reduce repeat RNA levels from both strands and the derived poly-dipeptides, rescue global mRNA homeostasis and improve survival of C9ORF72-ALS/FTD patient iPSC-derived neurons.}, } @article {pmid37364449, year = {2023}, author = {Fan, J and Li, Y and Niu, J and Liu, J and Guan, Y and Cui, L and Liu, M}, title = {The cross-sectional area of peripheral nerve in amyotrophic lateral sclerosis: A case-control study.}, journal = {Clinical neurology and neurosurgery}, volume = {231}, number = {}, pages = {107847}, doi = {10.1016/j.clineuro.2023.107847}, pmid = {37364449}, issn = {1872-6968}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnostic imaging ; Case-Control Studies ; Peripheral Nerves/diagnostic imaging ; Median Nerve/diagnostic imaging ; Spinal Nerve Roots ; }, abstract = {OBJECTIVE: A growing body of literature recognises the importance of peripheral nerve ultrasound in neuromuscular disorders. Several attempts have been made to differentiate amyotrophic lateral sclerosis (ALS) from multifocal motor neuropathy (MMN) using peripheral nerve ultrasound. A much-debated question is whether the cross-sectional area (CSA) of peripheral nerve in ALS patients is significantly smaller compared to healthy controls. This study aims to determine the CSA of peripheral nerves in patients with ALS.

METHODS: One hundred and thirty-nine patients with ALS and 75 healthy controls were recruited. Ultrasound of the median, ulnar, and trunks of the brachial plexus and cervical nerve roots was undertaken in ALS patients and controls.

RESULTS: Compared to controls, ALS patients had mild reductions of the median nerve, most sites of the ulnar nerve, trunks of the brachial plexus and cervical nerve roots. Another important finding of this study is that the median nerve tends to have a more significant reduction than the ulnar nerve in ALS patients, especially at the proximal.

CONCLUSIONS: Ultrasound could be sensitive to nerve motor fibre loss in patients with ALS. CSA at the proximal Median nerve may be a promising biomarker in patients with ALS.}, } @article {pmid37363576, year = {2023}, author = {Aderinto, N and Muili AbdulBasit, O and Afolayan, O and Jolayemi, MM}, title = {Current status and future directions of amyotrophic lateral sclerosis research in Africa: a perspective.}, journal = {Annals of medicine and surgery (2012)}, volume = {85}, number = {6}, pages = {3204-3208}, pmid = {37363576}, issn = {2049-0801}, abstract = {Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease with a global burden. Despite significant strides in ALS research, challenges facing ALS research in Africa are substantial. This paper discusses the current status and future directions of ALS research in Africa. Challenges and opportunities for ALS research in the region are highlighted, including limited funding and resources, the need for collaboration, and capacity building. Emerging technologies in ALS research in Africa are described, including telemedicine, neuroimaging, and genetic studies. Priorities for future ALS research in Africa are identified, including epidemiological studies, developing culturally appropriate diagnostic and management tools, and clinical trials of emerging treatments. Addressing these priorities will be critical to advancing ALS research and improving patient outcomes in Africa.}, } @article {pmid37363428, year = {2022}, author = {Sienes Bailo, P and Llorente Martín, E and Calmarza, P and Montolio Breva, S and Bravo Gómez, A and Pozo Giráldez, A and Sánchez-Pascuala Callau, JJ and Vaquer Santamaría, JM and Dayaldasani Khialani, A and Cerdá Micó, C and Camps Andreu, J and Sáez Tormo, G and Fort Gallifa, I}, title = {The role of oxidative stress in neurodegenerative diseases and potential antioxidant therapies.}, journal = {Advances in laboratory medicine}, volume = {3}, number = {4}, pages = {342-360}, pmid = {37363428}, issn = {2628-491X}, abstract = {OBJECTIVES: The central nervous system (CNS) is essential for homeostasis and controls the physiological functions of the body. However, the biochemical characteristics of the CNS make it especially vulnerable to oxidative damage (OS). This phenomenon compromises correct CNS functioning, leading to neurodegeneration and neuronal death.

CONTENTS: OS plays a crucial role in the physiopathology of neurodegenerative diseases. It is involved in multiple mechanisms of nucleic acid, protein, and lipid oxidation, thereby contributing to progressive brain damage. These mechanisms include mitochondrial dysfunction; excessive production of reactive oxygen and nitrogen species; deficiency of antioxidant defenses; protein oligomerization; cytokine production and inflammatory response; blood-brain barrier abnormalities; and proteasome dysfunction. All these dysfunctions are involved in the pathogenesis of neurodegenerative diseases, including Parkinson's disease, Alzheimer's disease, Huntington's disease, or amyotrophic lateral sclerosis.

SUMMARY AND OUTLOOK: A curative treatment is currently not available. Research is focused on the search for therapies that reduce oxidative damage and delay disease progression. In the recent years, researchers have focused their attention on the effects of antioxidant therapies.}, } @article {pmid37360345, year = {2023}, author = {Iijima, K and Watanabe, H and Nakashiro, Y and Iida, Y and Nonaka, M and Moriwaka, F and Hamada, S}, title = {Long-term effects of the gait treatment using a wearable cyborg hybrid assistive limb in a patient with spinal and bulbar muscular atrophy: a case report with 5 years of follow-up.}, journal = {Frontiers in neurology}, volume = {14}, number = {}, pages = {1143820}, pmid = {37360345}, issn = {1664-2295}, abstract = {BACKGROUND: Spinal and bulbar muscular atrophy (SBMA) is a progressive neuromuscular degenerative disease characterized by the degeneration of lower motor neurons in the spinal cord and brainstem and neurogenic atrophy of the skeletal muscle. Although the short-term effectiveness of gait treatment using a wearable cyborg hybrid assistive limb (HAL) has been demonstrated for the rehabilitation of patients with SBMA, the long-term effects of this treatment are unclear. Thus, this study aimed to investigate the long-term effects of the continued gait treatment with HAL in a patient with SBMA.

RESULTS: A 68-year-old man with SBMA had lower limb muscle weakness and atrophy, gait asymmetry, and decreased walking endurance. The patient performed nine courses of HAL gait treatment (as one course three times per week for 3 weeks, totaling nine times) for ~5 years. The patient performed HAL gait treatment to improve gait symmetry and endurance. A physical therapist adjusted HAL based on the gait analysis and physical function of the patient. Outcome measurements, such as 2-min walking distance (2MWD), 10-meter walking test (maximal walking speed, step length, cadence, and gait symmetry), muscle strength, Revised Amyotrophic Lateral Sclerosis Functional Assessment Scale (ALSFRS-R), and patient-reported outcomes, were evaluated immediately before and after gait treatment with HAL for each course. 2MWD improved from 94 m to 101.8 m, and the ALSFRS-R gait items remained unchanged (score 3) for approximately 5 years. The patient could maintain walking ability in terms of gait symmetry, walking endurance, and independence walking despite disease progression during HAL treatment.

CONCLUSION: The long-term gait treatment with HAL in a patient with SBMA may contribute to the maintenance and improvement of the gait endurance and ability to perform activities of daily living. The cybernics treatment using HAL may enable patients to relearn correct gait movements. The gait analysis and physical function assessment by a physical therapist might be important to maximize the benefits of HAL treatment.}, } @article {pmid37360176, year = {2023}, author = {Borg, R and Herrera, P and Purkiss, A and Cacciottolo, R and Cauchi, RJ}, title = {Reduced levels of ALS gene DCTN1 induce motor defects in Drosophila.}, journal = {Frontiers in neuroscience}, volume = {17}, number = {}, pages = {1164251}, pmid = {37360176}, issn = {1662-4548}, abstract = {Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neuromuscular disease that has a strong genetic component. Deleterious variants in the DCTN1 gene are known to be a cause of ALS in diverse populations. DCTN1 encodes the p150 subunit of the molecular motor dynactin which is a key player in the bidirectional transport of cargos within cells. Whether DCTN1 mutations lead to the disease through either a gain or loss of function mechanism remains unresolved. Moreover, the contribution of non-neuronal cell types, especially muscle tissue, to ALS phenotypes in DCTN1 carriers is unknown. Here we show that gene silencing of Dctn1, the Drosophila main orthologue of DCTN1, either in neurons or muscles is sufficient to cause climbing and flight defects in adult flies. We also identify Dred, a protein with high homology to Drosophila Dctn1 and human DCTN1, that on loss of function also leads to motoric impairments. A global reduction of Dctn1 induced a significant reduction in the mobility of larvae and neuromuscular junction (NMJ) deficits prior to death at the pupal stage. RNA-seq and transcriptome profiling revealed splicing alterations in genes required for synapse organisation and function, which may explain the observed motor dysfunction and synaptic defects downstream of Dctn1 ablation. Our findings support the possibility that loss of DCTN1 function can lead to ALS and underscore an important requirement for DCTN1 in muscle in addition to neurons.}, } @article {pmid37358634, year = {2023}, author = {Dubbioso, R and Provitera, V and Pacella, D and Santoro, L and Manganelli, F and Nolano, M}, title = {Autonomic dysfunction is associated with disease progression and survival in amyotrophic lateral sclerosis: a prospective longitudinal cohort study.}, journal = {Journal of neurology}, volume = {270}, number = {10}, pages = {4968-4977}, pmid = {37358634}, issn = {1432-1459}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis ; Longitudinal Studies ; Prospective Studies ; Disease Progression ; *Primary Dysautonomias ; }, abstract = {BACKGROUND: Among non-motor symptoms, autonomic disturbances have been described in amyotrophic lateral sclerosis (ALS) and reported as mild to moderate in up to 75% of patients. However, no study has systematically investigated autonomic symptoms as prognostic factors.

OBJECTIVES: The main aim of this longitudinal study was to examine the association of autonomic dysfunction with disease progression and survival in ALS.

METHODS: We enrolled newly diagnosed ALS patients and a healthy control group (HC). Time from disease onset to disease milestone (King's stage 4) and death were calculated to assess disease progression and survival. Autonomic symptoms were assessed by a dedicated questionnaire. Longitudinal evaluation of parasympathetic cardiovascular activity was performed by the heart rate variability (HRV). Multivariable Cox proportional hazards regression models on the risk of the disease milestone and death were used. A mixed-effect linear regression model was used to compare autonomic dysfunction with a HC group as well as its impairment over time.

RESULTS: A total of 102 patients and 41 HC were studied. ALS patients, compared with HC, complained of more autonomic symptoms, especially in bulbar onset patients. Autonomic symptoms occurred in 69 (68%) patients at diagnosis and progressed over time (post-6: p = 0.015 and post-12: p < 0.001). A higher autonomic symptom burden was an independent marker of faster development of King's stage 4 (HR 1.05; 95% CI 1.00-1.11; p = 0.022); whereas, urinary complaints were independent factors of a shorter survival (HR 3.12; 95% CI 1.22-7.97; p = 0.018). Moreover, HRV in ALS patients was lower than in HC (p = 0.018) and further decreased over time (p = 0.003), implying a parasympathetic hypofunction that progressed over time.

CONCLUSION: Autonomic symptoms occur in most of the ALS patients at diagnosis and progress over time, implying that autonomic dysfunction represents an intrinsic non-motor feature of the disease. A higher autonomic burden is a poor prognostic factor, associated with a more rapid development of disease milestones and shorter survival.}, } @article {pmid37358003, year = {2024}, author = {Canever, JB and Queiroz, LY and Soares, ES and de Avelar, NCP and Cimarosti, HI}, title = {Circadian rhythm alterations affecting the pathology of neurodegenerative diseases.}, journal = {Journal of neurochemistry}, volume = {168}, number = {8}, pages = {1475-1489}, doi = {10.1111/jnc.15883}, pmid = {37358003}, issn = {1471-4159}, support = {//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; //Coordenação de Aperfeiçoamento de Pessoal de Nível Superior/ ; }, mesh = {Humans ; *Neurodegenerative Diseases/physiopathology/pathology/metabolism ; *Circadian Rhythm/physiology ; Animals ; }, abstract = {The circadian rhythm is a nearly 24-h oscillation found in various physiological processes in the human brain and body that is regulated by environmental and genetic factors. It is responsible for maintaining body homeostasis and it is critical for essential functions, such as metabolic regulation and memory consolidation. Dysregulation in the circadian rhythm can negatively impact human health, resulting in cardiovascular and metabolic diseases, psychiatric disorders, and premature death. Emerging evidence points to a relationship between the dysregulation circadian rhythm and neurodegenerative diseases, suggesting that the alterations in circadian function might play crucial roles in the pathogenesis and progression of neurodegenerative diseases. Better understanding this association is of paramount importance to expand the knowledge on the pathophysiology of neurodegenerative diseases, as well as, to provide potential targets for the development of new interventions based on the dysregulation of circadian rhythm. Here we review the latest findings on dysregulation of circadian rhythm alterations in Parkinson's disease, Alzheimer's disease, Huntington's disease, amyotrophic lateral sclerosis, multiple sclerosis, spinocerebellar ataxia and multiple-system atrophy, focusing on research published in the last 3 years.}, } @article {pmid37356043, year = {2023}, author = {Nguyen, QT and Thanh, LN and Hoang, VT and Phan, TTK and Heke, M and Hoang, DM}, title = {Bone Marrow-Derived Mononuclear Cells in the Treatment of Neurological Diseases: Knowns and Unknowns.}, journal = {Cellular and molecular neurobiology}, volume = {43}, number = {7}, pages = {3211-3250}, pmid = {37356043}, issn = {1573-6830}, mesh = {Humans ; *Autism Spectrum Disorder ; Bone Marrow ; *Stroke/therapy ; Bone Marrow Cells ; }, abstract = {Bone marrow-derived mononuclear cells (BMMNCs) have been used for decades in preclinical and clinical studies to treat various neurological diseases. However, there is still a knowledge gap in the understanding of the underlying mechanisms of BMMNCs in the treatment of neurological diseases. In addition, prerequisite factors for the efficacy of BMMNC administration, such as the optimal route, dose, and number of administrations, remain unclear. In this review, we discuss known and unknown aspects of BMMNCs, including the cell harvesting, administration route and dose; mechanisms of action; and their applications in neurological diseases, including stroke, cerebral palsy, spinal cord injury, traumatic brain injury, amyotrophic lateral sclerosis, autism spectrum disorder, and epilepsy. Furthermore, recommendations on indications for BMMNC administration and the advantages and limitations of BMMNC applications for neurological diseases are discussed. BMMNCs in the treatment of neurological diseases. BMMNCs have been applied in several neurological diseases. Proposed mechanisms for the action of BMMNCs include homing, differentiation and paracrine effects (angiogenesis, neuroprotection, and anti-inflammation). Further studies should be performed to determine the optimal cell dose and administration route, the roles of BMMNC subtypes, and the indications for the use of BMMNCs in neurological conditions with and without genetic abnormalities.}, } @article {pmid37356024, year = {2023}, author = {Heinrich, F and Cordts, I and Günther, R and Stolte, B and Zeller, D and Schröter, C and Weyen, U and Regensburger, M and Wolf, J and Schneider, I and Hermann, A and Metelmann, M and Kohl, Z and Linker, RA and Koch, JC and Radelfahr, F and Schönfelder, E and Gardt, P and Mohajer-Peseschkian, T and Osmanovic, A and Klopstock, T and Dorst, J and Ludolph, AC and Schöffski, O and Boentert, M and Hagenacker, T and Deschauer, M and Lingor, P and Petri, S and Schreiber-Katz, O}, title = {Economic evaluation of Motor Neuron Diseases: a nationwide cross-sectional analysis in Germany.}, journal = {Journal of neurology}, volume = {270}, number = {10}, pages = {4922-4938}, pmid = {37356024}, issn = {1432-1459}, mesh = {Humans ; Quality of Life ; Cost of Illness ; Cross-Sectional Studies ; *Amyotrophic Lateral Sclerosis ; Cost-Benefit Analysis ; Surveys and Questionnaires ; Health Care Costs ; Germany/epidemiology ; *Muscular Atrophy, Spinal ; }, abstract = {BACKGROUND AND OBJECTIVES: Motor Neuron Diseases (MND) are rare diseases but have a high impact on affected individuals and society. This study aims to perform an economic evaluation of MND in Germany.

METHODS: Primary patient-reported data were collected including individual impairment, the use of medical and non-medical resources, and self-rated Health-Related Quality of Life (HRQoL). Annual socio-economic costs per year as well as Quality-Adjusted Life Years (QALYs) were calculated.

RESULTS: 404 patients with a diagnosis of Amyotrophic Lateral Sclerosis (ALS), Spinal Muscular Atrophy (SMA) or Hereditary Spastic Paraplegia (HSP) were enrolled. Total annual costs per patient were estimated at 83,060€ in ALS, 206,856€ in SMA and 27,074€ in HSP. The main cost drivers were informal care (all MND) and disease-modifying treatments (SMA). Self-reported HRQoL was best in patients with HSP (mean EuroQoL Five Dimension Five Level (EQ-5D-5L) index value 0.67) and lowest in SMA patients (mean EQ-5D-5L index value 0.39). QALYs for patients with ALS were estimated to be 1.89 QALYs, 23.08 for patients with HSP and 14.97 for patients with SMA, respectively. Cost-utilities were estimated as follows: 138,960€/QALY for ALS, 525,033€/QALY for SMA, and 49,573€/QALY for HSP. The main predictors of the high cost of illness and low HRQoL were disease progression and loss of individual autonomy.

CONCLUSION: As loss of individual autonomy was the main cost predictor, therapeutic and supportive measures to maintain this autonomy may contribute to reducing high personal burden and also long-term costs, e.g., care dependency and absenteeism from work.}, } @article {pmid37355220, year = {2023}, author = {Balog, BM and Sonti, A and Zigmond, RE}, title = {Neutrophil biology in injuries and diseases of the central and peripheral nervous systems.}, journal = {Progress in neurobiology}, volume = {228}, number = {}, pages = {102488}, pmid = {37355220}, issn = {1873-5118}, support = {F32 NS122918/NS/NINDS NIH HHS/United States ; R01 NS114891/NS/NINDS NIH HHS/United States ; }, mesh = {Humans ; *Neutrophils ; *Axons/physiology ; Nerve Regeneration/physiology ; Peripheral Nervous System ; Biology ; }, abstract = {The role of inflammation in nervous system injury and disease is attracting increased attention. Much of that research has focused on microglia in the central nervous system (CNS) and macrophages in the peripheral nervous system (PNS). Much less attention has been paid to the roles played by neutrophils. Neutrophils are part of the granulocyte subtype of myeloid cells. These cells, like macrophages, originate and differentiate in the bone marrow from which they enter the circulation. After tissue damage or infection, neutrophils are the first immune cells to infiltrate into tissues and are directed there by specific chemokines, which act on chemokine receptors on neutrophils. We have reviewed here the basic biology of these cells, including their differentiation, the types of granules they contain, the chemokines that act on them, the subpopulations of neutrophils that exist, and their functions. We also discuss tools available for identification and further study of neutrophils. We then turn to a review of what is known about the role of neutrophils in CNS and PNS diseases and injury, including stroke, Alzheimer's disease, multiple sclerosis, amyotrophic lateral sclerosis, spinal cord and traumatic brain injuries, CNS and PNS axon regeneration, and neuropathic pain. While in the past studies have focused on neutrophils deleterious effects, we will highlight new findings about their benefits. Studies on their actions should lead to identification of ways to modify neutrophil effects to improve health.}, } @article {pmid37354387, year = {2023}, author = {Garbuzova-Davis, S and Borlongan, CV}, title = {Transplanted Human Bone Marrow Endothelial Progenitor Cells Prolong Functional Benefits and Extend Survival of ALS Mice Likely via Blood-Spinal Cord Barrier Repair.}, journal = {Stem cell reviews and reports}, volume = {19}, number = {7}, pages = {2284-2291}, pmid = {37354387}, issn = {2629-3277}, support = {1R01NS090962/NH/NIH HHS/United States ; 1R01NS090962/NH/NIH HHS/United States ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a multifactorial disease with one of these factors being an impaired blood-spinal cord barrier (BSCB). In order to block harmful components in systemic circulation from accessing the CNS, barrier damage needs alleviation. Recently, we found that symptomatic ALS animals treated with intravenously delivered human bone marrow-derived CD34+ (hBM34+) cells or endothelial progenitor cells (hBMEPCs) showed delayed disease progression for 4 weeks post-transplant via BSCB repair. However, despite noted benefits from transplanted human bone marrow-derived stem cells, long-term effects of transplanted cells in ALS mice remain undetermined. This study aimed to determine prolonged effects of single equal doses of hBM34[+] cells and hBMEPCs systemically transplanted into symptomatic G93A SOD1 mice on behavioral disease outcomes and mouse lifespan. Results showed that transplanted hBMEPCs better ameliorated disease behavioral outcomes than hBM34 + cells until near end-stage disease and significantly increased lifespan vs. media-treated mice. These results provide important evidence that transplanted hBMEPCs prolonged functional benefits and extended survival of ALS mice, potentially by repairing the damaged BSCB. However, due to modestly increased lifespan of hBMEPC-treated mice, repeated cell transplants into symptomatic ALS mice may more effectively delay motor function deficit and extend lifespan by continuous reparative processes via replacement of damaged endothelial cells during disease progression.}, } @article {pmid37354059, year = {2023}, author = {Stikvoort García, DJL and Sleutjes, BTHM and van Schelven, LJ and Goedee, HS and van den Berg, LH}, title = {Diagnostic accuracy of nerve excitability and compound muscle action potential scan derived biomarkers in amyotrophic lateral sclerosis.}, journal = {European journal of neurology}, volume = {30}, number = {10}, pages = {3068-3078}, doi = {10.1111/ene.15954}, pmid = {37354059}, issn = {1468-1331}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis ; Action Potentials/physiology ; *Motor Neuron Disease ; Muscle, Skeletal ; Gold ; }, abstract = {BACKGROUND AND PURPOSE: The lack of reliable early biomarkers still causes substantial diagnostic delays in amyotrophic lateral sclerosis (ALS). The aim was to assess the diagnostic accuracy of a novel electrophysiological protocol in patients with suspected motor neuron disease (MND).

METHODS: Consecutive patients with suspected MND were prospectively recruited at our tertiary referral centre for MND in Utrecht, The Netherlands. Procedures were performed in accordance with the Standards for Reporting of Diagnostic Accuracy. In addition to the standard diagnostic workup, an electrophysiological protocol of compound muscle action potential (CMAP) scans and nerve excitability tests was performed on patients' thenar muscles. The combined diagnostic yield of nerve excitability and CMAP scan based motor unit number estimation was compared to the Awaji and Gold Coast criteria and their added value was determined.

RESULTS: In all, 153 ALS or progressive muscular atrophy patients, 63 disease controls and 43 healthy controls were included. Our electrophysiological protocol had high diagnostic accuracy (area under the curve [AUC] 0.85, 95% confidence interval [95% CI] 0.80-0.90), even in muscles with undetectable axon loss (AUC 0.78, 95% CI 0.70-0.85) and in bulbar-onset patients (AUC 0.85, 95% CI 0.73-0.95). Twenty-four of 33 (73%) ALS patients who could not be diagnosed during the same visit were correctly identified, as well as 8/13 (62%) ALS patients not meeting the Gold Coast criteria and 49/59 (83%) ALS patients not meeting the Awaji criteria during this first visit.

CONCLUSIONS: Our practical and non-invasive electrophysiological protocol may improve early diagnosis in clinically challenging patients with suspected ALS. Routine incorporation may boost early diagnosis, enhance patient selection and generate baseline measures for clinical trials.}, } @article {pmid37353279, year = {2023}, author = {van Eenennaam, RM and Kruithof, W and Beelen, A and Bakker, LA and van Eijk, RPA and Maessen, M and Baardman, JF and Visser-Meily, JMA and Veldink, JH and van den Berg, LH}, title = {Frequency of euthanasia, factors associated with end-of-life practices, and quality of end-of-life care in patients with amyotrophic lateral sclerosis in the Netherlands: a population-based cohort study.}, journal = {The Lancet. Neurology}, volume = {22}, number = {7}, pages = {591-601}, doi = {10.1016/S1474-4422(23)00155-2}, pmid = {37353279}, issn = {1474-4465}, mesh = {Male ; Female ; Humans ; *Amyotrophic Lateral Sclerosis/therapy ; Netherlands/epidemiology ; Cohort Studies ; Quality of Life ; *Neurodegenerative Diseases/complications ; *Terminal Care ; *Suicide, Assisted ; Death ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis is a progressive and lethal neurodegenerative disease that is at the forefront of debates on regulation of assisted dying. Since 2002, when euthanasia was legally regulated in the Netherlands, the frequency of this end-of-life practice has increased substantially from 1·7% of all deaths in 1990 and 2005 to 4·5% in 2015. We aimed to investigate whether the frequency of euthanasia in patients with amyotrophic lateral sclerosis had similarly increased since 2002, and to assess the factors associated with end-of-life practices and the quality of end-of-life care in patients with this disease.

METHODS: Using data from the Netherlands ALS registry, we did a population-based cohort study of clinicians and informal caregivers of patients with amyotrophic lateral sclerosis to assess factors associated with end-of-life decision making and the quality of end-of-life care. We included individuals who were diagnosed with amyotrophic lateral sclerosis according to the revised El-Escorial criteria, and who died between Jan 1, 2014, and Dec 31, 2016. We calculated the frequency of euthanasia in patients with amyotrophic lateral sclerosis from reports made to euthanasia review committees (ERCs) between 2012 and 2020. Results were compared with clinic-based survey studies conducted in 1994-2005. End-of-life practices were end-of-life decisions by a clinician when hastening of death was considered as the potential, probable, or definite effect comprising euthanasia, physician-assisted suicide, ending of life without explicit request, forgoing life-prolonging treatment, and intensified alleviation of symptoms.

FINDINGS: Between Jan 1, 2012, and Dec 31, 2020, 4130 reports of death from amyotrophic lateral sclerosis were made to ERCs, of which 1014 were from euthanasia or physician-assisted suicide (mean frequency 25% [SD 3] per year). Sex and gender data were unavailable from the ERC registry. Of 884 patients with amyotrophic lateral sclerosis who died between Jan 1, 2014, and Dec 31, 2016, their treating clinician was identified for 731 and a caregiver was identified for 741, of whom 356 (49%) and 450 (61%), respectively, agreed to participate in the population-based survey study. According to clinicians, end-of-life practices were chosen by 280 (79%) of 356 patients with amyotrophic lateral sclerosis who died. The frequency of euthanasia in patients with amyotrophic lateral sclerosis in 2014-16 (141 [40%] of 356 deaths in patients with amyotrophic lateral sclerosis) was higher than in 1994-98 (35 [17%] of 203) and 2000-05 (33 [16%] of 209). Median survival of patients with amyotrophic lateral sclerosis from diagnosis was 15·9 months (95% CI 12·6-17·6) for those who chose euthanasia and 16·1 months (13·4-19·1) for those who did not choose euthanasia (hazard ratio 1·07, 95% CI 0·85-1·34; p=0·58). According to caregivers, compared with other end-of-life practices, patients with amyotrophic lateral sclerosis choosing euthanasia commonly reported reasons to hasten death as no chance of improvement (53 [56%] of 94 patients who chose euthanasia vs 28 [39%] of 72 patients who chose other end-of-life practices), loss of dignity (47 [50%] vs 15 [21%]), dependency (34 [36%] vs five [7%]), and fatigue or extreme weakness (41 [44%] vs 14 [20%]). According to caregivers, people with amyotrophic lateral sclerosis-whether they chose euthanasia or did not-were satisfied with the general quality (83 [93%] of 89 patients who chose euthanasia vs 73 [86%] of 85 patients who did not) and availability (85 [97%] of 88 vs 81 [91%] of 90) of end-of-life care.

INTERPRETATION: The proportion of patients with amyotrophic lateral sclerosis who chose euthanasia in the Netherlands has increased since 2002. The choice of euthanasia was not associated with disease or patient characteristics, depression or hopelessness, or the availability or quality of end-of-life care. The choice of euthanasia had no effect on overall survival. Future studies could focus on the effect of discussing end-of-life options on quality of life as part of multidisciplinary care throughout the course of the disease, to reduce feelings of loss of autonomy and dignity in patients living with amyotrophic lateral sclerosis.

FUNDING: Netherlands ALS Foundation.}, } @article {pmid37353271, year = {2023}, author = {Hardiman, O}, title = {End-of-life decision making in amyotrophic lateral sclerosis.}, journal = {The Lancet. Neurology}, volume = {22}, number = {7}, pages = {547-548}, doi = {10.1016/S1474-4422(23)00193-X}, pmid = {37353271}, issn = {1474-4465}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy ; Death ; Quality of Life ; Decision Making ; }, } @article {pmid37352984, year = {2023}, author = {Yang, B and Pan, J and Zhang, XN and Wang, H and He, L and Rong, X and Li, X and Peng, Y}, title = {NRF2 activation suppresses motor neuron ferroptosis induced by the SOD1[G93A] mutation and exerts neuroprotection in amyotrophic lateral sclerosis.}, journal = {Neurobiology of disease}, volume = {184}, number = {}, pages = {106210}, doi = {10.1016/j.nbd.2023.106210}, pmid = {37352984}, issn = {1095-953X}, mesh = {Animals ; Humans ; Mice ; *Amyotrophic Lateral Sclerosis/metabolism ; Disease Models, Animal ; *Ferroptosis ; Mice, Transgenic ; Motor Neurons/metabolism ; Mutation/genetics ; *Neurodegenerative Diseases/metabolism ; Neuroprotection ; NF-E2-Related Factor 2/metabolism ; Superoxide Dismutase/genetics ; Superoxide Dismutase-1/genetics/metabolism ; }, abstract = {The progressive neurodegenerative disease amyotrophic lateral sclerosis (ALS) is caused by a decline in motor neuron function, resulting in worsened motor impairments, malnutrition, respiratory failure and mortality, and there is a lack of effective clinical treatments. The exact mechanism of motor neuronal degeneration remains unclear. Previously, we reported that ferroptosis, which is characterized by the accumulation of lipid peroxide and glutathione depletion in an iron-dependent manner, contributed to motor neuronal death in ALS cell models with the hSOD1[G93A] (human Cu/Zn-superoxide dismutase) gene mutation. In this study, we further explored the role of ferroptosis in motor neurons and its regulation in mutant hSOD1[G93A] cell and mouse models. Our results showed that ferroptosis was activated in hSOD1[G93A] NSC-34 cells and mouse models, which was accompanied by decreased nuclear retention of nuclear factor erythroid 2-related factor 2 (NRF2) and downregulation of solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4) levels. Moreover, RTA-408, an NRF2 activator, inhibited ferroptosis in hSOD1[G93A] NSC-34 cells by upregulating the protein expression of SLC7A11 and GPX4. Moreover, hSOD1[G93A] mice treated with RTA-408 showed obvious improvements in body weight and motor function. Our study demonstrated that ferroptosis contributed to the toxicity of motor neurons and that activating NRF2 could alleviate neuronal degeneration in ALS with the hSOD1[G93A] mutation.}, } @article {pmid37352136, year = {2023}, author = {Fukushi, M and Ohsawa, R and Okinaka, Y and Oikawa, D and Kiyono, T and Moriwaki, M and Irie, T and Oda, K and Kamei, Y and Tokunaga, F and Sotomaru, Y and Maruyama, H and Kawakami, H and Sakaguchi, T}, title = {Optineurin deficiency impairs autophagy to cause interferon beta overproduction and increased survival of mice following viral infection.}, journal = {PloS one}, volume = {18}, number = {6}, pages = {e0287545}, pmid = {37352136}, issn = {1932-6203}, mesh = {Animals ; Humans ; Mice ; *Amyotrophic Lateral Sclerosis/genetics ; Autophagy/genetics ; *Cell Cycle Proteins/genetics ; Immunity, Innate ; Interferon-beta/genetics ; Transcription Factor TFIIIA/genetics/metabolism ; *Virus Diseases ; *Membrane Transport Proteins/genetics ; Mice, Knockout ; }, abstract = {BACKGROUND: Optineurin (OPTN) is associated with several human diseases, including amyotrophic lateral sclerosis (ALS), and is involved in various cellular processes, including autophagy. Optineurin regulates the expression of interferon beta (IFNβ), which plays a central role in the innate immune response to viral infection. However, the role of optineurin in response to viral infection has not been fully clarified. It is known that optineurin-deficient cells produce more IFNβ than wild-type cells following viral infection. In this study, we investigate the reasons for, and effects of, IFNβ overproduction during optineurin deficiency both in vitro and in vivo.

METHODS: To investigate the mechanism of IFNβ overproduction, viral nucleic acids in infected cells were quantified by RT-qPCR and the autophagic activity of optineurin-deficient cells was determined to understand the basis for the intracellular accumulation of viral nucleic acids. Moreover, viral infection experiments using optineurin-disrupted (Optn-KO) animals were performed with several viruses.

RESULTS: IFNβ overproduction following viral infection was observed not only in several types of optineurin-deficient cell lines but also in Optn-KO mice and human ALS patient cells carrying mutations in OPTN. IFNβ overproduction in Optn-KO cells was revealed to be caused by excessive accumulation of viral nucleic acids, which was a consequence of reduced autophagic activity caused by the loss of optineurin. Additionally, IFNβ overproduction in Optn-KO mice suppressed viral proliferation, resulting in increased mouse survival following viral challenge.

CONCLUSION: Our findings indicate that the combination of optineurin deficiency and viral infection leads to IFNβ overproduction in vitro and in vivo. The effects of optineurin deficiency are elicited by viral infection, therefore, viral infection may be implicated in the development of optineurin-related diseases.}, } @article {pmid37351379, year = {2023}, author = {, }, title = {Erratum: Autophagy and neurodegeneration: unraveling the role of C9ORF72 in the regulation of autophagy and its relationship to ALS-FTD pathology.}, journal = {Frontiers in cellular neuroscience}, volume = {17}, number = {}, pages = {1225439}, doi = {10.3389/fncel.2023.1225439}, pmid = {37351379}, issn = {1662-5102}, abstract = {[This corrects the article DOI: 10.3389/fncel.2023.1086895.].}, } @article {pmid37351305, year = {2023}, author = {Lins, J and Brock, TJ and Hopkins, CE and Hart, AC}, title = {Generation of a C. elegans tdp-1 null allele and humanized TARDBP containing human disease-variants.}, journal = {microPublication biology}, volume = {2023}, number = {}, pages = {}, pmid = {37351305}, issn = {2578-9430}, support = {R43 AG061978/AG/NIA NIH HHS/United States ; }, abstract = {Clinical variants of TARDBP are associated with frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS) and other degenerative diseases. The predicted C. elegans ortholog of TARDBP is encoded by tdp-1 , but functional orthology has not been demonstrated in vivo. We undertook CRISPR/Cas9-based genome editing of the tdp-1 locus to create a complete loss of function allele; all tdp-1 exons and introns were deleted, creating tdp-1(tgx58) , which resulted in neurodegeneration after oxidative stress. Next, we undertook CRISPR-based genome editing to replace tdp-1 exons with human TARDBP coding sequences, creating humanized (hTARDBP) C. elegans expressing TDP-43 . Based on the efficiency of this genome editing, we suggest that iterative genome editing of the tdp-1 target locus using linked coCRISPR markers, like dpy-10 , would be a more efficient strategy for sequential assembly of the large engineered transgenes. hTARDBP decreased the neurodegeneration defect of tdp-1(tgx58) , demonstrating functional cross-species orthology. To develop C. elegans models of FTD and ALS, we inserted five different patient TARDBP variants in the C. elegans hTARDBP locus. Only one clinical variant increased stress-induced neurodegeneration; other variants caused inconsistent or negligible defects under these conditions. Combined, this work yielded an unambiguous null allele for tdp-1 , a validated, humanized hTARDBP, and multiple ALS/FTD patient-associated variant models that can be used for future studies.}, } @article {pmid37350671, year = {2023}, author = {Kalnmals, CA and Benko, ZL and Hamza, A and Bravo-Altamirano, K and Siddall, TL and Zielinski, M and Takano, HK and Riar, DS and Satchivi, NM and Roth, JJ and Church, JB}, title = {A New Class of Diaryl Ether Herbicides: Structure-Activity Relationship Studies Enabled by a Rapid Scaffold Hopping Approach.}, journal = {Journal of agricultural and food chemistry}, volume = {71}, number = {47}, pages = {18171-18187}, doi = {10.1021/acs.jafc.3c01285}, pmid = {37350671}, issn = {1520-5118}, mesh = {*Herbicides/pharmacology ; Ether ; Structure-Activity Relationship ; Ethers/pharmacology ; Plant Weeds/metabolism ; Ethyl Ethers ; *Acetolactate Synthase/metabolism ; Herbicide Resistance ; }, abstract = {We report on the development of a novel class of diaryl ether herbicides. After the discovery of a phenoxybenzoic acid with modest herbicidal activity, optimization led to several molecules with improved control of broadleaf and grass weeds. To facilitate this process, we first employed a three-step combinatorial approach, then pivoted to a one-step Ullmann-type coupling that provided faster access to new analogs. After determining that the primary target site of our benchmark diaryl ethers was acetolactate synthase (ALS), we further leveraged this copper-catalyzed methodology to conduct a scaffold hopping campaign in the hope of uncovering an additional mode of action with fewer documented cases of resistance. Our comprehensive and systematic investigation revealed that while the herbicidal activity of this area seems to be exclusively linked to ALS inhibition, our molecules represent a structurally distinct class of Group 2 herbicides. The structure-activity relationships that led us to this conclusion are described herein.}, } @article {pmid37350306, year = {2023}, author = {Zhou, J and Zeng, Q and Liao, Q and Niu, Q and Gu, W and Su, D and Li, S and Xiao, B and Bi, F}, title = {Biomarkers in cerebrospinal fluid for amyotrophic lateral sclerosis phenotypes.}, journal = {Annals of clinical and translational neurology}, volume = {10}, number = {8}, pages = {1467-1480}, pmid = {37350306}, issn = {2328-9503}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/cerebrospinal fluid ; Proteomics ; HLA-DR alpha-Chains ; *Neurodegenerative Diseases ; Biomarkers/cerebrospinal fluid ; Phenotype ; }, abstract = {OBJECTIVE: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease involving both upper and lower motor neurons. The motor phenotypes of ALS are highly clinically heterogeneous, and the underlying mechanisms are poorly understood.

METHODS: A comparative proteomic analysis was performed in the cerebrospinal fluid (CSF) of bulbar-onset (BO) and spinal-onset (SO) ALS patients and controls (n = 14). Five biomarker candidates were selected from a differentially regulated protein pool, and further validation was performed in a larger independent cohort (n = 92) using enzyme-linked immunosorbent assay (ELISA).

RESULTS: A total of 1732 CSF proteins were identified, and 78 differentially expressed proteins were found among BO-ALS patients, SO-ALS patients, and controls. Five promising biomarker candidates were selected for further validation, and lipopolysaccharide-binding protein (LBP) and HLA class II histocompatibility antigen, DR alpha chain (HLA-DRA) were validated. CSF LBP levels were increased in ALS patients compared with controls and higher in BO-ALS versus SO-ALS. The increased CSF LBP levels were correlated with the revised ALS Functional Scale (ALSFRS-R) score. CSF HLA-DRA levels were specifically elevated in BO-ALS patients, and there was no significant difference between SO-ALS patients and controls. Increased HLA-DRA expression was correlated with decreased survival.

INTERPRETATION: Our data shows that elevated CSF LBP is a good biomarker for ALS and correlates with clinical severity, and increased HLA-DRA is a specific biomarker for BO-ALS and may predict short survival. It also suggests that the microglial pathway and HLA-II-related adaptive immunity may be differentially involved in ALS phenotypes and may be new therapeutic targets for ALS.}, } @article {pmid37349911, year = {2023}, author = {Trojsi, F and Di Nardo, F and D'Alvano, G and Passaniti, C and Sharbafshaaer, M and Canale, F and Russo, A and Silvestro, M and Lavorgna, L and Cirillo, M and Esposito, F and Tedeschi, G and Siciliano, M}, title = {Cognitive, behavioral, and brain functional connectivity correlates of fatigue in amyotrophic lateral sclerosis.}, journal = {Brain and behavior}, volume = {13}, number = {7}, pages = {e2931}, pmid = {37349911}, issn = {2162-3279}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/complications/diagnostic imaging ; *Persons with Disabilities ; *Motor Disorders ; Brain ; Magnetic Resonance Imaging/methods ; Mental Fatigue/diagnostic imaging/etiology ; Cognition ; }, abstract = {INTRODUCTION: Fatigue is defined as a symptom of exhaustion unexplained by drug effects or psychiatric disorders and comprises two main components (i.e., central or "mental" and peripheral or "physical" components), both influencing global disability in amyotrophic lateral sclerosis (ALS). We aim at investigating the clinical correlations between "physical" and "mental" components of fatigue, measured by the Multidimensional Fatigue Inventory scale, and motor and cognitive/behavioral disability in a large sample of patients with ALS. We also investigated the correlations between these measures of fatigue and resting-state functional connectivity of brain functional magnetic resonance imaging (RS-fMRI) large-scale networks in a subset of patients.

METHODS: One hundred and thirty ALS patients were assessed for motor disability, cognitive and behavioral dysfunctions, fatigue, anxiety, apathy, and daytime sleepiness. Moreover, the collected clinical parameters were correlated with RS-fMRI functional connectivity changes in the large-scale brain networks of 30 ALS patients who underwent MRI.

RESULTS: Multivariate correlation analysis revealed that "physical" fatigue was related to anxiety and respiratory dysfunction, while "mental" fatigue was related to memory impairment and apathy. Moreover, the mental fatigue score was directly related to functional connectivity in the right and left insula (within the salience network), and inversely related to functional connectivity in the left middle temporal gyrus (within the default mode network).

CONCLUSIONS: Although the "physical" component of fatigue may be influenced by the disease itself, in ALS the "mental" component of fatigue correlates with cognitive and behavioral impairment, as well as with alterations of functional connectivity in extra-motor networks.}, } @article {pmid37349906, year = {2023}, author = {Shojaie, A and Rota, S and Al Khleifat, A and Ray Chaudhuri, K and Al-Chalabi, A}, title = {Non-motor symptoms in amyotrophic lateral sclerosis: lessons from Parkinson's disease.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {}, number = {}, pages = {1-10}, doi = {10.1080/21678421.2023.2220748}, pmid = {37349906}, issn = {2167-9223}, abstract = {Amyotrophic lateral sclerosis and Parkinson's disease are neurodegenerative diseases of the motor system which are now recognized also to affect non-motor pathways. Non-motor symptoms have been acknowledged as important determinants of quality of life in Parkinson's disease, and there is increasing interest in understanding the extent and role of non-motor symptoms in amyotrophic lateral sclerosis. We therefore reviewed what is known about non-motor symptoms in amyotrophic lateral sclerosis, using lessons from Parkinson's disease.}, } @article {pmid37348646, year = {2023}, author = {Lone, MA and Zeng, S and Bourquin, F and Wang, M and Huang, S and Lin, Z and Tang, B and Zhang, R and Hornemann, T}, title = {SPTLC1 p.Leu38Arg, a novel mutation associated with childhood ALS.}, journal = {Biochimica et biophysica acta. Molecular and cell biology of lipids}, volume = {1868}, number = {9}, pages = {159359}, doi = {10.1016/j.bbalip.2023.159359}, pmid = {37348646}, issn = {1879-2618}, mesh = {Female ; Humans ; Child ; *Amyotrophic Lateral Sclerosis/genetics ; HEK293 Cells ; Sphingolipids/metabolism ; Mutation ; Serine C-Palmitoyltransferase/genetics/metabolism ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neuromuscular disease. Recently, several gain-of-function mutations in SPTLC1 were associated with juvenile ALS. SPTLC1 encodes for a subunit of the serine-palmitoyltransferase (SPT) - the rate-limiting enzyme in the de novo synthesis of sphingolipids (SL). SPT activity, and thus SL de novo synthesis, is tightly controlled by a homeostatic feedback mechanism mediated by ORMDL proteins. Here we report a novel SPTLC1p.L38R mutation in a young Chinese girl with a signature of juvenile ALS. The patient presented with muscular weakness and atrophy, tongue tremor and fasciculation, breathing problems and positive pyramidal signs. All SPTLC1-ALS mutations including the SPTLC1 p.L38R are located within a single membrane-spanning domain of the protein and impede the interaction with the regulatory ORMDL subunit of SPT. Pertinent to the altered homeostatic control, lipid analysis showed overall increased SL levels in the patient plasma. An increased SPT activity and SL de novo synthesis was confirmed in p.L38R expressing HEK293 cells. Particularily dihydro-sphingolipids (dhSL) were signficantly increased in patient plasma and p.L38R mutant expressing cells. Increased dhSL formation has been previously linked to neurotoxicity and may be involved in the pathomechanism of SPTLC1-ALS mutations.}, } @article {pmid37346932, year = {2023}, author = {Monnakgotla, NR and Mahungu, AC and Heckmann, JM and Botha, G and Mulder, NJ and Wu, G and Rampersaud, E and Myers, J and Van Blitterswijk, M and Rademakers, R and Taylor, JP and Wuu, J and Benatar, M and Nel, M}, title = {Analysis of Structural Variants Previously Associated With ALS in Europeans Highlights Genomic Architectural Differences in Africans.}, journal = {Neurology. Genetics}, volume = {9}, number = {4}, pages = {e200077}, pmid = {37346932}, issn = {2376-7839}, abstract = {BACKGROUND AND OBJECTIVES: Amyotrophic lateral sclerosis (ALS) is a degenerative condition of the brain and spinal cord in which protein-coding variants in known ALS disease genes explain a minority of sporadic cases. There is a growing interest in the role of noncoding structural variants (SVs) as ALS risk variants or genetic modifiers of ALS phenotype. In small European samples, specific short SV alleles in noncoding regulatory regions of SCAF4, SQSTM1, and STMN2 have been reported to be associated with ALS, and several groups have investigated the possible role of SMN1/SMN2 gene copy numbers in ALS susceptibility and clinical severity.

METHODS: Using short-read whole genome sequencing (WGS) data, we investigated putative ALS-susceptibility SCAF4 (3'UTR poly-T repeat), SQSTM1 (intron 5 AAAC insertion), and STMN2 (intron 3 CA repeat) alleles in African ancestry patients with ALS and described the architecture of the SMN1/SMN2 gene region. South African cases with ALS (n = 114) were compared with ancestry-matched controls (n = 150), 1000 Genomes Project samples (n = 2,336), and H3Africa Genotyping Chip Project samples (n = 347).

RESULTS: There was no association with previously reported SCAF4 poly-T repeat, SQSTM1 AAAC insertion, and long STMN2 CA alleles with ALS risk in South Africans (p > 0.2). Similarly, SMN1 and SMN2 gene copy numbers did not differ between South Africans with ALS and matched population controls (p > 0.9). Notably, 20% of the African samples in this study had no SMN2 gene copies, which is a higher frequency than that reported in Europeans (approximately 7%).

DISCUSSION: We did not replicate the reported association of SCAF4, SQSTM1, and STMN2 short SVs with ALS in a small South African sample. In addition, we found no link between SMN1 and SMN2 copy numbers and susceptibility to ALS in this South African sample, which is similar to the conclusion of a recent meta-analysis of European studies. However, the SMN gene region findings in Africans replicate previous results from East and West Africa and highlight the importance of including diverse population groups in disease gene discovery efforts. The clinically relevant differences in the SMN gene architecture between African and non-African populations may affect the effectiveness of targeted SMN2 gene therapy for related diseases such as spinal muscular atrophy.}, } @article {pmid37346371, year = {2023}, author = {Lorenzini, I and Alsop, E and Levy, J and Gittings, LM and Lall, D and Rabichow, BE and Moore, S and Pevey, R and Bustos, LM and Burciu, C and Bhatia, D and Singer, M and Saul, J and McQuade, A and Tzioras, M and Mota, TA and Logemann, A and Rose, J and Almeida, S and Gao, FB and Marks, M and Donnelly, CJ and Hutchins, E and Hung, ST and Ichida, J and Bowser, R and Spires-Jones, T and Blurton-Jones, M and Gendron, TF and Baloh, RH and Van Keuren-Jensen, K and Sattler, R}, title = {Moderate intrinsic phenotypic alterations in C9orf72 ALS/FTD iPSC-microglia despite the presence of C9orf72 pathological features.}, journal = {Frontiers in cellular neuroscience}, volume = {17}, number = {}, pages = {1179796}, pmid = {37346371}, issn = {1662-5102}, support = {RF1 NS101986/NS/NINDS NIH HHS/United States ; R01 NS097545/NS/NINDS NIH HHS/United States ; R21 NS119952/NS/NINDS NIH HHS/United States ; I01 BX003625/BX/BLRD VA/United States ; T32 NS007433/NS/NINDS NIH HHS/United States ; T32 NS082174/NS/NINDS NIH HHS/United States ; P30 AG019610/AG/NIA NIH HHS/United States ; R01 NS101986/NS/NINDS NIH HHS/United States ; R01 NS120331/NS/NINDS NIH HHS/United States ; }, abstract = {While motor and cortical neurons are affected in C9orf72 amyotrophic lateral sclerosis and frontotemporal dementia (ALS/FTD), it remains largely unknown if and how non-neuronal cells induce or exacerbate neuronal damage. We differentiated C9orf72 ALS/FTD patient-derived induced pluripotent stem cells into microglia (iPSC-MG) and examined their intrinsic phenotypes. Similar to iPSC motor neurons, C9orf72 ALS/FTD iPSC-MG mono-cultures form G4C2 repeat RNA foci, exhibit reduced C9orf72 protein levels, and generate dipeptide repeat proteins. Healthy control and C9orf72 ALS/FTD iPSC-MG equally express microglial specific genes and perform microglial functions, including inflammatory cytokine release and phagocytosis of extracellular cargos, such as synthetic amyloid beta peptides and healthy human brain synaptoneurosomes. RNA sequencing analysis revealed select transcriptional changes of genes associated with neuroinflammation or neurodegeneration in diseased microglia yet no significant differentially expressed microglial-enriched genes. Moderate molecular and functional differences were observed in C9orf72 iPSC-MG mono-cultures despite the presence of C9orf72 pathological features suggesting that a diseased microenvironment may be required to induce phenotypic changes in microglial cells and the associated neuronal dysfunction seen in C9orf72 ALS/FTD neurodegeneration.}, } @article {pmid37345437, year = {2023}, author = {Rush, CL and Lester, EG and Manglani, H and Woodworth, E and Vitolo, O and Fava, M and Berry, JD and Brizzi, K and Babu, S and Lindenberger, EC and Curtis, JR and Vranceanu, AM}, title = {Resilient together-ALS: leveraging the NDD transdiagnostic framework to develop an early dyadic intervention for people with amyotrophic lateral sclerosis and their informal care-partners.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {}, number = {}, pages = {1-8}, doi = {10.1080/21678421.2023.2224400}, pmid = {37345437}, issn = {2167-9223}, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive weakness and eventual death, usually within 3-5 years. An ALS diagnosis is associated with substantial emotional distress for both the affected person and their family care-partners which impairs the ability to engage in important conversations about long term care planning, negatively impacts ALS symptoms for the patient, and quality of life for both patient and care-partner. Here we 1) discuss published works identified by the authors about psychosocial interventions for the ALS population, 2) identify a lack of early, dyadic interventions to support psychosocial needs of people with ALS and care-partners; 3) describe the Neurodegenerative Diseases (NDD) framework for early dyadic intervention development and 4) propose an adaptation of an evidence-based early dyadic psychosocial intervention, Recovering Together, for the unique needs of people with ALS and their care-partners (Resilient Together-ALS; RT-ALS) using the NDD framework. Future work will use stakeholder feedback to optimize the intervention for subsequent efficacy testing.}, } @article {pmid37345346, year = {2023}, author = {Donohue, C and Chapin, JL and Anderson, A and DiBiase, L and Gray, LT and Wymer, JP and Plowman, EK}, title = {Sensitivity and specificity of the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised to detect dysarthria in individuals with amyotrophic lateral sclerosis.}, journal = {Muscle & nerve}, volume = {68}, number = {3}, pages = {296-302}, pmid = {37345346}, issn = {1097-4598}, support = {R01 NS100859/NS/NINDS NIH HHS/United States ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/complications/diagnosis ; Dysarthria/diagnosis/etiology ; Severity of Illness Index ; Sensitivity and Specificity ; ROC Curve ; }, abstract = {INTRODUCTION/AIMS: Given the widespread use of the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) to measure disease progression in ALS and recent reports demonstrating its poor sensitivity, we aimed to determine the sensitivity and specificity of the ALSFRS-R bulbar subscale and speech item to detect validated clinical ratings of dysarthria in individuals with ALS.

METHODS: Paired ALSFRS-R and validated Speech Intelligibility Test (SIT) data from individuals with ALS were analyzed. Trained raters completed duplicate, independent, and blinded ratings of audio recordings to obtain speech intelligibility (%) and speaking rate (words per minute, WPM). Binary dysarthria profiles were derived (dysarthria ≤96% intelligible and/or <150 WPM). Data were obtained using the Kruskal-Wallis test, receiver-operating characteristic (ROC) curve, area under the curve (AUC), sensitivity and specificity percentages, and positive/negative predictive values (PPV/NPV).

RESULTS: A total of 250 paired SIT and ALSFRS-R data points were analyzed. Dysarthria was confirmed in 72.4% (n = 181). Dysarthric speakers demonstrated lower ALSFRS-R bulbar subscale (8.9 vs. 11.2) and speech item (2.7 vs. 3.7) scores (P < .0001). The ALSFRS-R bulbar subscale score had an AUC of 0.81 (95% confidence interval [CI] 0.75 to 0.86). A subscale score of ≤11 yielded a sensitivity of 86%, specificity of 57%, PPV of 84%, and NPV of 60% to correctly identify dysarthria status. The ALSFRS-R speech item score demonstrated an AUC of 0.81 to detect dysarthria (95% CI 0.76 to 0.85), with sensitivity of 79%, specificity of 75%, PPV of 89%, and NPV of 58% for a speech item cutpoint of ≤3.

DISCUSSION: The ALSFRS-R bulbar and speech item subscale scores may be useful, inexpensive, and quick tools for monitoring dysarthria status in ALS.}, } @article {pmid37345246, year = {2023}, author = {Li, X and Tian, Y and Wu, H and Wang, T}, title = {Network Pharmacology and Molecular Docking to Unveil the Mechanism of Shudihuang against Amyotrophic Lateral Sclerosis.}, journal = {Current pharmaceutical design}, volume = {29}, number = {19}, pages = {1535-1545}, doi = {10.2174/1381612829666230621105552}, pmid = {37345246}, issn = {1873-4286}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy ; Molecular Docking Simulation ; Network Pharmacology ; Sitosterols ; Cyclooxygenase 2 ; PPAR gamma ; Stigmasterol ; *Drugs, Chinese Herbal/pharmacology/therapeutic use ; Medicine, Chinese Traditional ; }, abstract = {BACKGROUND: Shudihuang has been clinically proven to be an effective Chinese medicine compatible with the treatment of amyotrophic lateral sclerosis. However, the underlying mechanism of Shudihuang against amyotrophic lateral sclerosis remains unclear.

OBJECTIVES: The present study aims to elucidate the possible mechanism of Shudihuang in treating ALS using network pharmacology and molecular docking.

METHODS: The primary active components of Shudihuang and their relevant targets were identified by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and the Swiss Target Prediction database, respectively. The ALS-related targets were obtained from the Disgenet and OMIM databases. The shared targets were derived by the intersection of disease-associated and component-associated targets and then introduced into the Cytoscape software to construct a network of drug-component-target. In addition, protein interaction relationships among the shared targets were analyzed by the STRING and Cytoscape software. Furthermore, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) functional enrichment analysis were conducted by the Metascape platform. The binding activities between the hub targets and the active components were assessed with molecular docking.

RESULTS: Stigmasterol and sitosterol were identified as the core components of Shudihuang, and the hub targets of ALS are PTGS2, PPARG, ESR1, IGF-1R, and MAPK3, with the highest degrees in the PPI network. The finding that stigmasterol and sitosterol had a good affinity with PTGS2, PPARG, ESR1, IGF-1R, and MAPK3 also supported this. Finally, it was revealed that Shudihuang treatment of ALS predominantly involves estrogen- related pathways such as nuclear receptor activity and steroid binding.

CONCLUSION: In summary, this study suggested that the main active components of Shudihuang (stigmasterol and sitosterol) may exert a critical effect in ALS treatment by binding to hub targets (PTGS2, PPARG, ESR1, IGF-1R, and MAPK3) and then modulating estrogen receptor-related pathways to attenuate glutamate excitotoxicity, inhibit oxidative stress and antagonize inflammation.}, } @article {pmid37344897, year = {2023}, author = {Dweikat, IM and Gelli, M and Bernards, M and Martin, A and Jhala, A}, title = {Mutations in the acetolactate synthase (ALS) enzyme affect shattercane (Sorghum bicolor) response to ALS-inhibiting herbicides.}, journal = {Hereditas}, volume = {160}, number = {1}, pages = {28}, pmid = {37344897}, issn = {1601-5223}, mesh = {*Acetolactate Synthase/genetics/metabolism ; *Sorghum ; *Herbicides/pharmacology ; Herbicide Resistance/genetics ; Mutation ; Plant Proteins/genetics ; }, abstract = {BACKGROUND: Shattercane [Sorghum bicolor (L.) Moench ssp. Arundinaceum (Desv.)] is a competitive weed in North America's corn, soybean, sorghum, and other agronomic crops. Control of shattercane with POST herbicides in corn became possible with the introduction of acetolactate synthase (ALS)-inhibiting herbicides in the 1980s, and their extensive use resulted in the evolution of ALS-inhibitors resistant shattercane.

RESULTS: Shattercane seeds were collected from 16 south-eastern and south-central Nebraska fields that were treated with primisulfuron for three consecutive years. Three resistant plants were found in greenhouse evaluations of more than 30,000 plants. Results from a greenhouse bioassay conducted to assess the response of each shattercane biotype to ALS-inhibiting herbicides showed a differential response to ALS inhibitors within and between chemical classes. Biotype P8-30 was resistant or partially resistant to all ALS-inhibiting herbicides applied and displayed a unique amino acid sequence substitution (Trp574 to Leu) relative to the other two resistant biotypes, P2-205 and P9-102. Whole plant dose-response studies confirmed a 4- to the 12-fold level of primisulfuron resistance in three shattercane biotypes compared with the known primisulfuron-susceptible shattercane biotype. The ALS gene was sequenced using primers designed from the corn ALS sequence to identify mutations in the ALS gene that confer resistance. A total of seven nucleotide substitutions were detected in the three herbicide-resistant biotypes P2-205, P8-30, and P9-102. These biotypes are being crossed to adapted sorghum lines (grain, sweet, and forage) to broaden germplasm with resistance to ALS-inhibiting herbicides.

CONCLUSION: The discovery of these mutants should accelerate the development of sorghum genotypes that tolerate ALS-based herbicides, which provide additional choices for sorghum farmers to control weeds, especially grasses, in their fields.}, } @article {pmid37344230, year = {2023}, author = {Bjornevik, K and Cortese, M and Furtado, JD and Paganoni, S and Schwarzschild, MA and Cudkowicz, ME and Ascherio, A}, title = {Association of Polyunsaturated Fatty Acids and Clinical Progression in Patients With ALS: Post Hoc Analysis of the EMPOWER Trial.}, journal = {Neurology}, volume = {101}, number = {7}, pages = {e690-e698}, pmid = {37344230}, issn = {1526-632X}, mesh = {Male ; Humans ; Middle Aged ; Female ; *Amyotrophic Lateral Sclerosis/drug therapy ; Fatty Acids, Unsaturated ; *Fatty Acids, Omega-3 ; Fatty Acids, Omega-6 ; Disease Progression ; Fatty Acids ; }, abstract = {BACKGROUND AND OBJECTIVES: Polyunsaturated fatty acids (PUFAs) have neuroprotective and anti-inflammatory effects and could be beneficial in amyotrophic lateral sclerosis (ALS). Higher dietary intake and plasma levels of PUFAs, in particular alpha-linolenic acid (ALA), have been associated with a lower risk of ALS in large epidemiologic cohort studies, but data on disease progression in patients with ALS are sparse. We examined whether plasma levels of ALA and other PUFAs contributed to predicting survival time and functional decline in patients with ALS.

METHODS: We conducted a study among participants in the EMPOWER clinical trial who had plasma samples collected at the time of randomization that were available for fatty acid analyses. Plasma fatty acids were measured using gas chromatography. We used Cox proportional hazards models and linear regression to evaluate the association of individual fatty acids with risk of death and joint rank test score of functional decline and survival.

RESULTS: Fatty acid analyses were conducted in 449 participants. The mean (SD) age of these participants at baseline was 57.5 (10.7) years, and 293 (65.3%) were men; 126 (28.1%) died during follow-up. Higher ALA levels were associated with lower risk of death (age-adjusted and sex-adjusted hazard ratio comparing highest vs lowest quartile 0.50, 95% CI 0.29-0.86, p-trend = 0.041) and higher joint rank test score (difference in score according to 1 SD increase 10.7, 95% CI 0.2-21.1, p = 0.045), consistent with a slower functional decline. The estimates remained similar in analyses adjusted for body mass index, race/ethnicity, symptom duration, site of onset, riluzole use, family history of ALS, predicted upright slow vital capacity, and treatment group. Higher levels of the n-3 fatty acid eicosapentaenoic acid and the n-6 fatty acid linoleic acid were associated with a lower risk of death during follow-up.

DISCUSSION: Higher levels of ALA were associated with longer survival and slower functional decline in patients with ALS. These results suggest that ALA may have a favorable effect on disease progression in patients with ALS.}, } @article {pmid37343857, year = {2023}, author = {Mauri, L and Tarolli, P}, title = {Modeling windthrow effects on water runoff and hillslope stability in a mountain catchment affected by the VAIA storm.}, journal = {The Science of the total environment}, volume = {895}, number = {}, pages = {164831}, doi = {10.1016/j.scitotenv.2023.164831}, pmid = {37343857}, issn = {1879-1026}, abstract = {Windthrows seriously affect forest landscapes, causing several issues in hydrological and geomorphological terms. In this regard, Airborne Laser Scanning (ALS) topographic data recently increased the opportunity to investigate in detail physical processes at the catchment scale. Moreover, topographically based hydrological and geomorphological models allow quantifying runoff alteration due to windthrows-driven land cover changes and detect the occurrence of land degradative processes at the sub-catchment scale. In this connection, accurate investigations about windthrows role in varying local runoff regimes over time are still obscure, as well as the possibility of predicting terrain instabilities due to windstorm occurrence. This research aims to investigate the interaction between windthrows, runoff alterations and hillslope failures affecting a landslide-prone mountain catchment (northern Italy). Hydrological HEC-HMS and geomorphological RESS models were applied. Windthrows' role in altering runoff regimes and hillslope stability was investigated starting from the elaboration of ALS-derived points clouds acquired before and after the occurrence of the Vaia storm. Digital Terrain Models (DTMs) were elaborated for the two scenarios to compare daily runoff variations and predict the activation of terrain instabilities by looking at land cover changes driven by the blowdown event at the sub-catchment detail. Results attested the key role of windstorms in altering local runoff, with a maximum relative runoff increment equal to 2.56 % and a maximum runoff difference equal to 3.12 mmh[-1], as well as in encouraging the activation of the observed shallow landslide. The correlation between windthrows occurrence and runoff alterations was validated by performing regression analysis (R[2] = 0.76), while the accuracy of instabilities predictions was tested through the Distance to Perfect Classification (D2PC) index and True Skill Statistic (TSS) score, respectively resulted equal to 0.076 and 0.898. This research represents a valid tool for investigating similar issues at a wider scale, also providing suggestions for promoting interventions in wind-disturbed forest areas.}, } @article {pmid37343835, year = {2023}, author = {Lilly, E and Hamilton, HK and Dover, JS}, title = {Response to Richey et al's "Psychiatric comorbidity and pharmacology in a cosmetic dermatology setting: A retrospective cohort study".}, journal = {Journal of the American Academy of Dermatology}, volume = {89}, number = {4}, pages = {e187}, doi = {10.1016/j.jaad.2023.02.068}, pmid = {37343835}, issn = {1097-6787}, mesh = {Humans ; *Dermatology ; Retrospective Studies ; Comorbidity ; }, } @article {pmid37343522, year = {2023}, author = {Zhou, ZD and Yi, LX and Tan, EK}, title = {Targeting gasdermin E in neurodegenerative diseases.}, journal = {Cell reports. Medicine}, volume = {4}, number = {6}, pages = {101075}, pmid = {37343522}, issn = {2666-3791}, mesh = {Humans ; Gasdermins ; *Neurodegenerative Diseases ; *Frontotemporal Dementia ; *Amyotrophic Lateral Sclerosis ; }, abstract = {Neel et al. identified pathophysiologic clues linking gasdermin-E (GSDME) with frontotemporal dementia and amyotrophic lateral sclerosis.[1] Therapeutic studies targeting GSDME may provide a viable approach for neurodegenerative diseases.}, } @article {pmid37342380, year = {2023}, author = {Shamsaei, G and Houshmand, F and Ahmadzadeh Deylami, A and Valizadeh, A and Rafie, S and Moradi, M}, title = {The Efficacy and Safety of Intrathecal Autologous Bone Marrow-Derived Mesenchymal Stromal Cells in Amyotrophic Lateral Sclerosis: A Pilot Study.}, journal = {Advanced pharmaceutical bulletin}, volume = {13}, number = {2}, pages = {361-367}, pmid = {37342380}, issn = {2228-5881}, abstract = {Purpose: Amyotrophic lateral sclerosis (ALS) is an uncommon and aggressive neurodegenerative disorder that influences the lower and upper motor neurons. There are low eligible drugs for ALS treatment; in this regard, supplemental and replacement treatments are essential. There are relative studies in the field of mesenchymal stromal cells (MSCs) therapy in ALS, but the different methods, differently used medium, and difference in follow-up periods affect the outcome treatment. Methods: The current survey is a single-center, phase I clinical trial to evaluating the efficacy and safety of autologous bone marrow (BM)-derived MSCs through intrathecal administration in ALS patients. MNCs were isolated from BM specimens and cultured. The clinical outcome was evaluated based Revised Amyotrophic Lateral Sclerosis Functional Rating (ALSFRS-R) Scale. Results: Each patient received 15±3×10[6] cells through subarachnoid space. No adverse events (AEs) were detected. Just one patient experienced a mild headache after injection. Following injection, no new intradural cerebrospinal pathology transplant-related was observed. None of the patients' pathologic disruptions following transplantation were detected by magnetic resonance imaging (MRI). The additional analyses have shown the average rate of ALSFRS-R score and forced vital capacity (FVC) reduction have decreased during 10 months following MSCs transplantation versus the pretreatment period, from -5.4±2.3 to -2±3.08 ALSFRS-R points/period (P=0.014) and -12.6±5.22% to -4.8±14.72%/period (P<0.001), respectively. Conclusion: These results have shown that autologous MSCs transplantation reduces the disease's progression and has favorable safety. Trial Registration: This study performed as a phase I clinical trial (code IRCT20200828048551N1).}, } @article {pmid37341302, year = {2023}, author = {Wang, Y and Wu, S and Li, Q and Sun, H and Wang, H}, title = {Pharmacological Inhibition of Ferroptosis as a Therapeutic Target for Neurodegenerative Diseases and Strokes.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {10}, number = {24}, pages = {e2300325}, pmid = {37341302}, issn = {2198-3844}, support = {81260196//National Natural Science Foundation of China/ ; 81450036//National Natural Science Foundation of China/ ; 2020YK02//Science Foundation of AMHT/ ; 2021YK05//Science Foundation of AMHT/ ; 2022YK01//Science Foundation of AMHT/ ; YN202104//Science Foundation of ASCH/ ; YN202305//Science Foundation of ASCH/ ; 2020MS08175//Natural Science Foundation of Inner Mongolia Autonomous Region/ ; 2021LHMS08024//Natural Science Foundation of Inner Mongolia Autonomous Region/ ; 2022MS08046//Natural Science Foundation of Inner Mongolia Autonomous Region/ ; YC202305//Science Foundation of Inner Mongolia Key Laboratory of human genetic diseases/ ; YC202304//Science Foundation of Inner Mongolia Key Laboratory of human genetic diseases/ ; }, mesh = {Humans ; *Ferroptosis ; *Neurodegenerative Diseases/drug therapy ; *Stroke/drug therapy ; Cell Death ; }, abstract = {Emerging evidence suggests that ferroptosis, a unique regulated cell death modality that is morphologically and mechanistically different from other forms of cell death, plays a vital role in the pathophysiological process of neurodegenerative diseases, and strokes. Accumulating evidence supports ferroptosis as a critical factor of neurodegenerative diseases and strokes, and pharmacological inhibition of ferroptosis as a therapeutic target for these diseases. In this review article, the core mechanisms of ferroptosis are overviewed and the roles of ferroptosis in neurodegenerative diseases and strokes are described. Finally, the emerging findings in treating neurodegenerative diseases and strokes through pharmacological inhibition of ferroptosis are described. This review demonstrates that pharmacological inhibition of ferroptosis by bioactive small-molecule compounds (ferroptosis inhibitors) could be effective for treatments of these diseases, and highlights a potential promising therapeutic avenue that could be used to prevent neurodegenerative diseases and strokes. This review article will shed light on developing novel therapeutic regimens by pharmacological inhibition of ferroptosis to slow down the progression of these diseases in the future.}, } @article {pmid37340732, year = {2023}, author = {Hsueh, SJ and Chao, CC and Chen, TF and Chen, YF and Hsueh, HW and Tsai, LK and Wu, WC and Hsieh, ST}, title = {Brain imaging signatures in amyotrophic lateral sclerosis: Correlation with peripheral motor degeneration.}, journal = {Annals of clinical and translational neurology}, volume = {10}, number = {8}, pages = {1456-1466}, pmid = {37340732}, issn = {2328-9503}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnostic imaging ; Diffusion Tensor Imaging/methods ; Brain/diagnostic imaging ; Magnetic Resonance Imaging ; Neuroimaging ; }, abstract = {OBJECTIVE: This study aimed to explore the clinical significance of brain imaging signatures in the context of clinical neurological deficits in association with upper and lower motor neuron degeneration in amyotrophic lateral sclerosis (ALS).

METHODS: We performed brain MRI examinations to quantitatively evaluate (1) gray matter volume and (2) white matter tract fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD), and mean diffusivity (MD). Image-derived indices were correlated with (1) global neurological deficits of MRC muscle strength sum score, revised amyotrophic lateral sclerosis functional rating scale (ALSFRS-R), and forced vital capacity (FVC), and (2) focal scores of University of Pennsylvania Upper motor neuron score (Penn score) and the summation of compound muscle action potential Z scores (CMAP Z sum score).

RESULTS: There were 39 ALS patients and 32 control subjects matched for age and gender. Compared to controls, ALS patients had a lower gray matter volume in the precentral gyrus of the primary motor cortex, which was correlated with FA of corticofugal tracts. The gray matter volume of the precentral gyrus was correlated with FVC, MRC sum score, and CMAP Z sum score, while the FA of the corticospinal tract was linearly associated with CMAP Z sum score and Penn score on multivariate linear regression model.

INTERPRETATION: This study indicated that clinical assessment of muscle strength and routine measurements on nerve conduction studies provided surrogate markers of brain structural changes for ALS. Furthermore, these findings suggested parallel involvement of both upper and lower motor neurons in ALS.}, } @article {pmid37340319, year = {2023}, author = {Ozzoude, M and Varriano, B and Beaton, D and Ramirez, J and Adamo, S and Holmes, MF and Scott, CJM and Gao, F and Sunderland, KM and McLaughlin, P and Goubran, M and Kwan, D and Roberts, A and Bartha, R and Symons, S and Tan, B and Swartz, RH and Abrahao, A and Saposnik, G and Masellis, M and Lang, AE and Marras, C and Zinman, L and Shoesmith, C and Borrie, M and Fischer, CE and Frank, A and Freedman, M and Montero-Odasso, M and Kumar, S and Pasternak, S and Strother, SC and Pollock, BG and Rajji, TK and Seitz, D and Tang-Wai, DF and Turnbull, J and Dowlatshahi, D and Hassan, A and Casaubon, L and Mandzia, J and Sahlas, D and Breen, DP and Grimes, D and Jog, M and Steeves, TDL and Arnott, SR and Black, SE and Finger, E and Rabin, J and , and Tartaglia, MC}, title = {White matter hyperintensities and smaller cortical thickness are associated with neuropsychiatric symptoms in neurodegenerative and cerebrovascular diseases.}, journal = {Alzheimer's research & therapy}, volume = {15}, number = {1}, pages = {114}, pmid = {37340319}, issn = {1758-9193}, mesh = {Humans ; Female ; *White Matter/diagnostic imaging ; *Frontotemporal Dementia ; *Parkinson Disease ; *Cognitive Dysfunction/psychology ; *Cerebrovascular Disorders/complications/diagnostic imaging ; Magnetic Resonance Imaging ; }, abstract = {BACKGROUND: Neuropsychiatric symptoms (NPS) are a core feature of most neurodegenerative and cerebrovascular diseases. White matter hyperintensities and brain atrophy have been implicated in NPS. We aimed to investigate the relative contribution of white matter hyperintensities and cortical thickness to NPS in participants across neurodegenerative and cerebrovascular diseases.

METHODS: Five hundred thirteen participants with one of these conditions, i.e. Alzheimer's Disease/Mild Cognitive Impairment, Amyotrophic Lateral Sclerosis, Frontotemporal Dementia, Parkinson's Disease, or Cerebrovascular Disease, were included in the study. NPS were assessed using the Neuropsychiatric Inventory - Questionnaire and grouped into hyperactivity, psychotic, affective, and apathy subsyndromes. White matter hyperintensities were quantified using a semi-automatic segmentation technique and FreeSurfer cortical thickness was used to measure regional grey matter loss.

RESULTS: Although NPS were frequent across the five disease groups, participants with frontotemporal dementia had the highest frequency of hyperactivity, apathy, and affective subsyndromes compared to other groups, whilst psychotic subsyndrome was high in both frontotemporal dementia and Parkinson's disease. Results from univariate and multivariate results showed that various predictors were associated with neuropsychiatric subsyndromes, especially cortical thickness in the inferior frontal, cingulate, and insula regions, sex(female), global cognition, and basal ganglia-thalamus white matter hyperintensities.

CONCLUSIONS: In participants with neurodegenerative and cerebrovascular diseases, our results suggest that smaller cortical thickness and white matter hyperintensity burden in several cortical-subcortical structures may contribute to the development of NPS. Further studies investigating the mechanisms that determine the progression of NPS in various neurodegenerative and cerebrovascular diseases are needed.}, } @article {pmid37340309, year = {2023}, author = {Yue, W and Deng, X and Wang, Z and Jiang, M and Hu, R and Duan, Y and Wang, Q and Cui, J and Fang, Y}, title = {Inhibition of the MEK/ERK pathway suppresses immune overactivation and mitigates TDP-43 toxicity in a Drosophila model of ALS.}, journal = {Immunity & ageing : I & A}, volume = {20}, number = {1}, pages = {27}, pmid = {37340309}, issn = {1742-4933}, support = {31970697//National Natural Science Foundation of China/ ; 201409003300//Science and Technology Commission of Shanghai Municipality/ ; }, abstract = {TDP-43 is an important DNA/RNA-binding protein that is associated with age-related neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD); however, its pathomechanism is not fully understood. In a transgenic RNAi screen using Drosophila as a model, we uncovered that knockdown (KD) of Dsor1 (the Drosophila MAPK kinase dMEK) suppressed TDP-43 toxicity without altering TDP-43 phosphorylation or protein levels. Further investigation revealed that the Dsor1 downstream gene rl (dERK) was abnormally upregulated in TDP-43 flies, and neuronal overexpression of dERK induced profound upregulation of antimicrobial peptides (AMPs). We also detected a robust immune overactivation in TDP-43 flies, which could be suppressed by downregulation of the MEK/ERK pathway in TDP-43 fly neurons. Furthermore, neuronal KD of abnormally increased AMPs improved the motor function of TDP-43 flies. On the other hand, neuronal KD of Dnr1, a negative regulator of the Drosophila immune deficiency (IMD) pathway, activated the innate immunity and boosted AMP expression independent of the regulation by the MEK/ERK pathway, which diminished the mitigating effect of RNAi-dMEK on TDP-43 toxicity. Finally, we showed that an FDA-approved MEK inhibitor trametinib markedly suppressed immune overactivation, alleviated motor deficits and prolonged the lifespan of TDP-43 flies, but did not exhibit a lifespan-extending effect in Alzheimer disease (AD) or spinocerebellar ataxia type 3 (SCA3) fly models. Together, our findings suggest an important role of abnormal elevation of the MEK/ERK signaling and innate immunity in TDP-43 pathogenesis and propose trametinib as a potential therapeutic agent for ALS and other TDP-43-related diseases.}, } @article {pmid37339631, year = {2023}, author = {Kume, K and Kurashige, T and Muguruma, K and Morino, H and Tada, Y and Kikumoto, M and Miyamoto, T and Akutsu, SN and Matsuda, Y and Matsuura, S and Nakamori, M and Nishiyama, A and Izumi, R and Niihori, T and Ogasawara, M and Eura, N and Kato, T and Yokomura, M and Nakayama, Y and Ito, H and Nakamura, M and Saito, K and Riku, Y and Iwasaki, Y and Maruyama, H and Aoki, Y and Nishino, I and Izumi, Y and Aoki, M and Kawakami, H}, title = {CGG repeat expansion in LRP12 in amyotrophic lateral sclerosis.}, journal = {American journal of human genetics}, volume = {110}, number = {7}, pages = {1086-1097}, pmid = {37339631}, issn = {1537-6605}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/pathology ; Motor Neurons/pathology ; *Muscular Dystrophies/genetics ; *Neurodegenerative Diseases/genetics ; C9orf72 Protein/genetics ; DNA Repeat Expansion ; Low Density Lipoprotein Receptor-Related Protein-1/genetics ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by the degeneration of motor neurons. Although repeat expansion in C9orf72 is its most common cause, the pathogenesis of ALS isn't fully clear. In this study, we show that repeat expansion in LRP12, a causative variant of oculopharyngodistal myopathy type 1 (OPDM1), is a cause of ALS. We identify CGG repeat expansion in LRP12 in five families and two simplex individuals. These ALS individuals (LRP12-ALS) have 61-100 repeats, which contrasts with most OPDM individuals with repeat expansion in LRP12 (LRP12-OPDM), who have 100-200 repeats. Phosphorylated TDP-43 is present in the cytoplasm of iPS cell-derived motor neurons (iPSMNs) in LRP12-ALS, a finding that reproduces the pathological hallmark of ALS. RNA foci are more prominent in muscle and iPSMNs in LRP12-ALS than in LRP12-OPDM. Muscleblind-like 1 aggregates are observed only in OPDM muscle. In conclusion, CGG repeat expansions in LRP12 cause ALS and OPDM, depending on the length of the repeat. Our findings provide insight into the repeat length-dependent switching of phenotypes.}, } @article {pmid37339001, year = {2023}, author = {Song, J and Dikwella, N and Sinske, D and Roselli, F and Knöll, B}, title = {SRF deletion results in earlier disease onset in a mouse model of amyotrophic lateral sclerosis.}, journal = {JCI insight}, volume = {8}, number = {15}, pages = {}, pmid = {37339001}, issn = {2379-3708}, mesh = {Animals ; Mice ; *Amyotrophic Lateral Sclerosis/genetics ; Etoposide ; Gene Expression Regulation ; Motor Neurons/physiology ; Serum Response Factor/genetics ; }, abstract = {Changes in neuronal activity modulate the vulnerability of motoneurons (MNs) in neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). So far, the molecular basis of neuronal activity's impact in ALS is poorly understood. Herein, we investigated the impact of deleting the neuronal activity-stimulated transcription factor (TF) serum response factor (SRF) in MNs of SOD1G93A mice. SRF was present in vulnerable MMP9+ MNs. Ablation of SRF in MNs induced an earlier disease onset starting around 7-8 weeks after birth, as revealed by enhanced weight loss and decreased motor ability. This earlier disease onset in SRF-depleted MNs was accompanied by a mild elevation of neuroinflammation and neuromuscular synapse degeneration, whereas overall MN numbers and mortality were unaffected. In SRF-deficient mice, MNs showed impaired induction of autophagy-encoding genes, suggesting a potentially new SRF function in transcriptional regulation of autophagy. Complementary, constitutively active SRF-VP16 enhanced autophagy-encoding gene transcription and autophagy progression in cells. Furthermore, SRF-VP16 decreased ALS-associated aggregate induction. Chemogenetic modulation of neuronal activity uncovered SRF as having important TF-mediating activity-dependent effects, which might be beneficial to reduce ALS disease burden. Thus, our data identify SRF as a gene regulator connecting neuronal activity with the cellular autophagy program initiated in degenerating MNs.}, } @article {pmid37338894, year = {2023}, author = {Burg, T and Van Den Bosch, L}, title = {Abnormal energy metabolism in ALS: a key player?.}, journal = {Current opinion in neurology}, volume = {36}, number = {4}, pages = {338-345}, pmid = {37338894}, issn = {1473-6551}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism ; *Neurodegenerative Diseases/pathology ; Motor Neurons/pathology ; Energy Metabolism ; Precision Medicine ; }, abstract = {PURPOSE OF THE REVIEW: Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disease of the motor system due to the selective and progressive degeneration of both upper and lower motor neurons. Disturbances in energy homeostasis were repeatedly associated with the ALS pathogenesis and appear early during the disease process. In this review, we highlight recent work demonstrating the crucial role of energy metabolism in ALS and discuss its potential clinical relevance.

RECENT FINDINGS: The alteration of various metabolic pathways contributes to the heterogeneity of the clinical phenotype of ALS. Recent work showed that different ALS mutations selectively impact these pathways and translate to the disease phenotypes in patients and disease models. Strikingly, a growing number of studies point towards an early, even presymptomatic, contribution of abnormal energy homeostasis to the ALS pathogenesis. Advances in metabolomics generated valuable tools to study altered metabolic pathways, to test their therapeutic potential, and to develop personalized medicine. Importantly, recent preclinical studies and clinical trials demonstrated that targeting energy metabolism is a promising therapeutic approach.

SUMMARY: Abnormal energy metabolism is a key player in ALS pathogenesis, emerging as a source of potential disease biomarkers and therapeutic targets.}, } @article {pmid37338836, year = {2023}, author = {Seefeldt, T and Aitzetmüller-Klietz, ML and Kückelhaus, M and Wiebringhaus, P and Hirsch, T and Harati, K and Aitzetmüller-Klietz, MM}, title = {[Liposuktion beim Lipödem - Doch besser als ihr Ruf?].}, journal = {Journal der Deutschen Dermatologischen Gesellschaft = Journal of the German Society of Dermatology : JDDG}, volume = {21}, number = {6}, pages = {601-610}, doi = {10.1111/ddg.15064_g}, pmid = {37338836}, issn = {1610-0387}, } @article {pmid37338820, year = {2023}, author = {Willemse, SW and van Es, MA}, title = {Susceptibility and disease modifier genes in amyotrophic lateral sclerosis: from genetic associations to therapeutic implications.}, journal = {Current opinion in neurology}, volume = {36}, number = {4}, pages = {365-370}, pmid = {37338820}, issn = {1473-6551}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy/drug therapy ; Genes, Modifier ; Superoxide Dismutase-1/genetics/therapeutic use ; Motor Neurons ; Mutation ; }, abstract = {PURPOSE OF REVIEW: Amyotrophic lateral sclerosis (ALS) is a severe disease characterized by the degeneration of motor neurons. Large-scale genetic studies have now identified over 60 genes that are associated with ALS, which in large part have also been functionally characterized. The purpose of this review is to outline how these advances are being translated into novel therapeutic strategies.

RECENT FINDINGS: The emergence of techniques that allow the specific therapeutic targeting of a (mutant) gene, in particular antisense oligonucleotide therapy (ASOs), have led to the first successful gene therapy for SOD1-ALS and multiple other gene-targeted trials are underway. This includes genetic variants that modify the disease phenotype as well as causal mutations.

SUMMARY: Technological and methodological advances are enabling researchers to unravel the genetics of ALS. Both causal mutations and genetic modifiers are viable therapeutic targets. By performing natural history studies, the phenotype-genotype correlations can be characterized. In conjunction with biomarkers for target engagement and international collaboration, this makes performing gene-targeted trials ALS feasible. The first effective treatment has now been developed for SOD1-ALS and, with multiple studies underway, it seems realistic that more therapies will follow.}, } @article {pmid37338613, year = {2023}, author = {Milella, G and Zoccolella, S and Giugno, A and Filardi, M and Urso, D and Nigro, S and Tafuri, B and Tamburrino, L and Gnoni, V and Logroscino, G}, title = {The impact of upper and lower motor neuron burden on diagnostic certainty, and clinical course of spinal-onset amyotrophic lateral sclerosis: a cluster-based approach.}, journal = {Journal of neurology}, volume = {270}, number = {10}, pages = {4868-4875}, pmid = {37338613}, issn = {1432-1459}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/epidemiology/complications ; Bayes Theorem ; Motor Neurons/physiology ; Prognosis ; Disease Progression ; }, abstract = {BACKGROUND: Upper motor neuron (UMN) and lower motor neuron (LMN) involvement represent the core clinical features of amyotrophic lateral sclerosis (ALS). Several studies divided patients into prevalent UMN and LMN impairment phenotypes to investigate the association between motor systems impairments and ALS clinical course. However, this distinction was somehow heterogeneous and significantly affected the comparability across studies.

AIMS: This study aimed to investigate whether patients spontaneously segregate based on the extent of UMN and LMN involvement without a-priori categorization and to identify potential clinical and prognostic features of different clusters.

METHODS: Eighty-eight consecutive spinal-onset ALS patients were referred to an ALS tertiary center between 2015 and 2022. UMN and LMN burden was assessed with the Penn Upper Motor Neuron scale (PUMNS) and the Devine score, respectively. PUMNS and LMN scores were normalized into 0-1 and analyzed using a two-step cluster analysis and the Euclidean distance measure. The Bayesian Information Criterion was used to determine the cluster number. Demographic and clinical variables were tested for differences among the clusters.

RESULTS: Three distinct clusters emerged at cluster analysis. Patients in "cluster-1" showed moderate UMN and severe LMN involvement, corresponding to the typical ALS phenotype. Patients in "cluster-2" showed mild LMN and severe UMN damage, corresponding to a predominant UMN phenotype, while "cluster-3" patients showed mild UMN and moderate LMN damage, corresponding to a predominant LMN phenotype. Patients in "cluster-1" and "cluster-2" showed a higher prevalence of definite ALS than those in "cluster-3" (61% and 46 vs 9%, p < 0.001). "Cluster-1" patients had a lower median ALSFRS-r score compared to both "cluster-2" and 3 patients (27 vs 40 and 35, < 0.001). "Cluster-1" (HR: 8.5; 95% CI 2.1-35.1 and p = 0.003) and 3 (HR: 3.2; 95% CI 1.1-9.1; p = 0.03) were associated with shorter survival than those in "cluster-2".

CONCLUSIONS: Spinal-onset ALS can be categorized into three groups according to LMN and UMN burden. The UMN burden is related to higher diagnostic certainty and broader disease spread, while LMN involvement is associated with higher disease severity and shorter survival.}, } @article {pmid37338307, year = {2023}, author = {Tripathi, SJ and Chakraborty, S and Miller, E and Pieper, AA and Paul, BD}, title = {Hydrogen sulfide signalling in neurodegenerative diseases.}, journal = {British journal of pharmacology}, volume = {}, number = {}, pages = {}, pmid = {37338307}, issn = {1476-5381}, support = {P30 AG062428/AG/NIA NIH HHS/United States ; R01 AG071512/AG/NIA NIH HHS/United States ; RO1AG066707/AG/NIA NIH HHS/United States ; 1 U01 AG073323/AG/NIA NIH HHS/United States ; RM1 GM142002/GM/NIGMS NIH HHS/United States ; U01 AG073323/AG/NIA NIH HHS/United States ; R01 AG066707/AG/NIA NIH HHS/United States ; T32 AG071474/AG/NIA NIH HHS/United States ; P50 DA044123/DA/NIDA NIH HHS/United States ; 1 P30 AGO62428-01/AG/NIA NIH HHS/United States ; R01AG071512/AG/NIA NIH HHS/United States ; I01 BX005976/BX/BLRD VA/United States ; 1R21AG073684-01/AG/NIA NIH HHS/United States ; DA044123/DA/NIDA NIH HHS/United States ; R21 AG073684/AG/NIA NIH HHS/United States ; }, abstract = {The gaseous neurotransmitter hydrogen sulfide (H2 S) exerts neuroprotective efficacy in the brain via post-translational modification of cysteine residues by sulfhydration, also known as persulfidation. This process is comparable in biological impact to phosphorylation and mediates a variety of signalling events. Unlike conventional neurotransmitters, H2 S cannot be stored in vesicles due to its gaseous nature. Instead, it is either locally synthesized or released from endogenous stores. Sulfhydration affords both specific and general neuroprotective effects and is critically diminished in several neurodegenerative disorders. Conversely, some forms of neurodegenerative disease are linked to excessive cellular H2 S. Here, we review the signalling roles of H2 S across the spectrum of neurodegenerative diseases, including Huntington's disease, Parkinson's disease, Alzheimer's disease, Down syndrome, traumatic brain injury, the ataxias, and amyotrophic lateral sclerosis, as well as neurodegeneration generally associated with ageing.}, } @article {pmid37337289, year = {2023}, author = {Nango, H and Tsuruta, K and Miyagishi, H and Aono, Y and Saigusa, T and Kosuge, Y}, title = {Update on the pathological roles of prostaglandin E2 in neurodegeneration in amyotrophic lateral sclerosis.}, journal = {Translational neurodegeneration}, volume = {12}, number = {1}, pages = {32}, pmid = {37337289}, issn = {2047-9158}, mesh = {Mice ; Animals ; *Amyotrophic Lateral Sclerosis/drug therapy/genetics/metabolism ; *Neurodegenerative Diseases/metabolism ; Motor Neurons/pathology ; Mice, Transgenic ; Dinoprostone/metabolism/pharmacology/therapeutic use ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by selective degeneration of upper and lower motor neurons. The pathogenesis of ALS remains largely unknown; however, inflammation of the spinal cord is a focus of ALS research and an important pathogenic process in ALS. Prostaglandin E2 (PGE2) is a major lipid mediator generated by the arachidonic-acid cascade and is abundant at inflammatory sites. PGE2 levels are increased in the postmortem spinal cords of ALS patients and in ALS model mice. Beneficial therapeutic effects have been obtained in ALS model mice using cyclooxygenase-2 inhibitors to inhibit the biosynthesis of PGE2, but the usefulness of this inhibitor has not yet been proven in clinical trials. In this review, we present current evidence on the involvement of PGE2 in the progression of ALS and discuss the potential of microsomal prostaglandin E synthase (mPGES) and the prostaglandin receptor E-prostanoid (EP) 2 as therapeutic targets for ALS. Signaling pathways involving prostaglandin receptors mediate toxic effects in the central nervous system. In some situations, however, the receptors mediate neuroprotective effects. Our recent studies demonstrated that levels of mPGES-1, which catalyzes the final step of PGE2 biosynthesis, are increased at the early-symptomatic stage in the spinal cords of transgenic ALS model mice carrying the G93A variant of superoxide dismutase-1. In addition, in an experimental motor-neuron model used in studies of ALS, PGE2 induces the production of reactive oxygen species and subsequent caspase-3-dependent cytotoxicity through activation of the EP2 receptor. Moreover, this PGE2-induced EP2 up-regulation in motor neurons plays a role in the death of motor neurons in ALS model mice. Further understanding of the pathophysiological role of PGE2 in neurodegeneration may provide new insights to guide the development of novel therapies for ALS.}, } @article {pmid37336982, year = {2023}, author = {Nikom, D and Zheng, S}, title = {Alternative splicing in neurodegenerative disease and the promise of RNA therapies.}, journal = {Nature reviews. Neuroscience}, volume = {24}, number = {8}, pages = {457-473}, pmid = {37336982}, issn = {1471-0048}, support = {R01 NS125276/NS/NINDS NIH HHS/United States ; }, mesh = {Humans ; Alternative Splicing/genetics ; RNA/genetics/metabolism ; *Neurodegenerative Diseases/genetics/therapy/metabolism ; RNA Splicing ; Protein Isoforms/genetics/metabolism ; *Amyotrophic Lateral Sclerosis ; *Frontotemporal Dementia/genetics ; }, abstract = {Alternative splicing generates a myriad of RNA products and protein isoforms of different functions from a single gene. Dysregulated alternative splicing has emerged as a new mechanism broadly implicated in the pathogenesis of neurodegenerative diseases such as Alzheimer disease, amyotrophic lateral sclerosis, frontotemporal dementia, Parkinson disease and repeat expansion diseases. Understanding the mechanisms and functional outcomes of abnormal splicing in neurological disorders is vital in developing effective therapies to treat mis-splicing pathology. In this Review, we discuss emerging research and evidence of the roles of alternative splicing defects in major neurodegenerative diseases and summarize the latest advances in RNA-based therapeutic strategies to target these disorders.}, } @article {pmid37336364, year = {2023}, author = {Di Maio, A and Nuzzo, T and Gilio, L and Serra, M and Buttari, F and Errico, F and De Rosa, A and Bassi, MS and Morelli, M and Sasabe, J and Sulzer, D and Carta, M and Centonze, D and Usiello, A}, title = {Homeostasis of serine enantiomers is disrupted in the post-mortem caudate putamen and cerebrospinal fluid of living Parkinson's disease patients.}, journal = {Neurobiology of disease}, volume = {184}, number = {}, pages = {106203}, doi = {10.1016/j.nbd.2023.106203}, pmid = {37336364}, issn = {1095-953X}, support = {R01 NS095435/NS/NINDS NIH HHS/United States ; }, mesh = {Humans ; *Parkinson Disease/metabolism ; Serine/metabolism ; Putamen/metabolism ; *Amyotrophic Lateral Sclerosis ; *Alzheimer Disease/metabolism ; Amino Acids ; Receptors, N-Methyl-D-Aspartate/metabolism ; N-Methylaspartate ; Homeostasis ; }, abstract = {L-serine generated in astrocytes plays a pivotal role in modulating essential neurometabolic processes, while its enantiomer, D-serine, specifically regulates NMDA receptor (NMDAR) signalling. Despite their physiological relevance in modulating cerebral activity, serine enantiomers metabolism in Parkinson's disease (PD) remains elusive. Using High-Performance Liquid Chromatography (HPLC), we measured D- and L-serine levels along with other amino acids known to modulate NMDAR function, such as L-glutamate, L-aspartate, D-aspartate, and glycine, in the post-mortem caudate putamen (CPu) and superior frontal gyrus (SFG) of PD patients. Moreover, we examined these amino acids in the cerebrospinal fluid (CSF) of de novo living PD, Alzheimer's disease (AD), and amyotrophic lateral sclerosis (ALS) patients versus subjects with other neurological disorders (OND), used as control. We found higher D-serine and L-serine levels in the CPu of PD patients but not in the SFG, a cerebral region that, in contrast to the CPu, is not innervated by nigral dopaminergic terminals. We also highlighted a significant elevation of both serine enantiomers in the CSF samples from PD but not in those of AD and ALS patients, compared with control subjects. By contrast, none or only minor changes were found in the amount of other NMDAR modulating amino acids. Our findings identify D-serine and L-serine level upregulation as a biochemical signature associated with nigrostriatal dopaminergic degeneration in PD.}, } @article {pmid37335771, year = {2023}, author = {Peters, B and Wiedrick, J and Baylor, C}, title = {Effects of Aided Communication on Communicative Participation for People With Amyotrophic Lateral Sclerosis.}, journal = {American journal of speech-language pathology}, volume = {32}, number = {4}, pages = {1450-1465}, pmid = {37335771}, issn = {1558-9110}, support = {R01 DC009834/DC/NIDCD NIH HHS/United States ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/complications ; Communication ; Speech ; Speech Disorders ; Dysarthria/diagnosis/etiology ; }, abstract = {PURPOSE: Many people with amyotrophic lateral sclerosis (PALS) experience speech changes, which may interfere with participation in communication situations. This study was designed to investigate the effects of aided communication on self-rated communicative participation among PALS and the relationship between speech function and communicative participation for PALS at various stages of speech impairment and communication aid use.

METHOD: Participants with amyotrophic lateral sclerosis completed an online questionnaire in which they identified their current communication methods, rated their speech function, and rated their communicative participation in various situations on a modified version of the Communicative Participation Item Bank short form. PALS who reported using aided communication rated their communicative participation under two conditions: with unaided communication only and with access to all of their communication methods.

RESULTS: Communication aids appeared to support communicative participation for many participants with dysarthria. Across all levels of speech function, PALS who use aided communication reported better participation under the all-methods condition than the unaided-only condition, with the largest benefits for participants with anarthria (Revised ALS Functional Rating Scale [ALSFRS-R] speech rating = 0). Communicative participation ratings worsened with more severe speech impairment under both conditions for most levels of speech function, but PALS with anarthria (ALSFRS-R speech rating = 0) reported better participation under the all-methods condition than those who used residual speech in combination with non speech methods (ALSFRS-R speech rating = 1).

CONCLUSIONS: Aided communication can help PALS continue to participate in various communication situations as their speech function deteriorates. Variability in self-rated communicative participation, even for PALS at the same level of speech function, highlights the need for an individualized approach and consideration of personal and environmental factors in augmentative and alternative communication intervention.

SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.22782986.}, } @article {pmid37335396, year = {2023}, author = {Dubbioso, R and Spisto, M and Hausdorff, JM and Aceto, G and Iuzzolino, VV and Senerchia, G and De Marco, S and Marcuccio, L and Femiano, C and Iodice, R and Salvatore, E and Santangelo, G and Trojano, L and Moretta, P}, title = {Cognitive impairment is associated with gait variability and fall risk in amyotrophic lateral sclerosis.}, journal = {European journal of neurology}, volume = {30}, number = {10}, pages = {3056-3067}, doi = {10.1111/ene.15936}, pmid = {37335396}, issn = {1468-1331}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/complications ; *Cognitive Dysfunction/complications ; Gait ; Walking ; Cognition ; }, abstract = {BACKGROUND: In amyotrophic lateral sclerosis (ALS), gait abnormalities contribute to poor mobility and represent a relevant risk for falls. To date, gait studies in ALS patients have focused on the motor dimension of the disease, underestimating the cognitive aspects.

METHODS: Using a wearable gait analysis device, we compared gait patterns in ambulatory ALS patients with mild cognitive impairment (ALS MCI+; n = 18), and without MCI (ALS MCI-; n = 24), and healthy subjects (HS; n = 16) under two conditions: (1) normal gait (single task) and (2) walking while counting backward (dual task). Finally, we examined if the occurrence and number of falls in the 3 months following the baseline test were related to cognition.

RESULTS: In the single task condition, ALS patients, regardless of cognition, displayed higher gait variability than HS, especially for stance and swing time (p < 0.001). The dual task condition revealed additional differences in gait variability parameters between ALS MCI+ and ALS MCI- for cadence (p = 0.005), stance time (p = 0.04), swing time (p = 0.04) and stability index (p = 0.02). Moreover, ALS MCI+ showed a higher occurrence (p = 0.001) and number of falls (p < 0.001) at the follow-up. Regression analyses demonstrated that MCI condition predicted the occurrence of future falls (β = 3.649; p = 0.01) and, together with executive dysfunction, was associated with the number of falls (cognitive impairment: β = 0.63; p < 0.001; executive dysfunction: β = 0.39; p = 0.03), regardless of motor impairment at clinical examination.

CONCLUSION: In ALS, MCI is associated with exaggerated gait variability and predicts the occurrence and number of short-term falls.}, } @article {pmid37334341, year = {2023}, author = {Galeazzi, L and Holzman, J and Mondoloni, M and Rochefort, J}, title = {Lingual fasciculation: A point of call for the diagnosis of amyotrophic lateral sclerosis.}, journal = {Clinical case reports}, volume = {11}, number = {6}, pages = {e7560}, pmid = {37334341}, issn = {2050-0904}, abstract = {A 60-year-old female patient, with no notable medical history, was referred by the internal medicine department for a dry mouth workup. The clinical examination revealed an absence of dryness, and the presence of lingual fasciculations, associated with difficulties in mastication and phonation. These symptoms appeared spontaneously 9 months before the consultation, after leaving confinement. Given the presence of lingual fasciculations, the diagnostic hypothesis of a neurological pathology, in particular amyotrophic lateral sclerosis (ALS), was suspected. After performing an electromyogram (EMG), the diagnosis of ALS was retained. Riluzole treatment was then started, and physical therapy sessions were scheduled. Riluzole allows an average gain of 4 to 6 months of life expectancy. Speech therapy and physical therapy allow to maintain the functions as long as possible and to improve the end-of-life conditions. The interest of early detection of ALS allows delaying the progression of the disease.}, } @article {pmid37334257, year = {2023}, author = {Sennfält, S and Aspegren, O and Engvall, M and Granberg, T and Piehl, F}, title = {Systemic Capillary Leak Syndrome With Cerebral Involvement in a C9orf72 Expansion Carrier: Case Report and Review of the Literature.}, journal = {Neurology. Genetics}, volume = {9}, number = {4}, pages = {e200081}, pmid = {37334257}, issn = {2376-7839}, abstract = {OBJECTIVE: Systemic capillary leak syndrome (SCLS) is a rare condition associated with episodes of hypotension, hemoconcentration, hypoalbuminemia, and rhabdomyolysis. We describe a middle-aged man presenting with several distinct SCLS-like episodes, the last being fatal. In addition, in the year before the final event, he developed rapid cognitive decline with contrast-enhancing lesions on MRI and highly elevated neurofilament light protein levels in CSF.

METHODS: Data and imaging were obtained from patient medical records.

RESULTS: At the time, the SCLS-like episodes were interpreted as myositis secondary to viral infection. A thorough workup for other causes, including genetic testing, was negative. As for the rapid cognitive decline, despite an extensive workup for infectious and inflammatory causes, no definitive diagnosis was made. Whole genome sequencing however identified a C9orf72 hexanucleotide expansion.

DISCUSSION: The C9orf72 expansion is associated with frontotemporal dementia and amyotrophic lateral sclerosis but has also been shown to increase susceptibility to neuroinflammation. Recent findings also suggest C9orf72 to exert functions in the immune system, in particular regulation of type I interferon responses, in turn shown to be associated with SCLS. This case suggests a possible link between SCLS, cerebral inflammation, dysregulated type I interferon signaling, and expansions in C9orf72.}, } @article {pmid37334170, year = {2023}, author = {Zhao, D and Ma, Y and Meng, J and Hu, Y and Hong, M and Zhang, J and Zuo, G and Lv, X and Liu, Y and Shi, C}, title = {MCR-ALS-based muscle synergy extraction method combined with LSTM neural network for motion intention detection.}, journal = {Frontiers in neurorobotics}, volume = {17}, number = {}, pages = {1174710}, pmid = {37334170}, issn = {1662-5218}, abstract = {INTRODUCTION: The time-varying and individual variability of surface electromyographic signals (sEMG) can lead to poorer motor intention detection results from different subjects and longer temporal intervals between training and testing datasets. The consistency of using muscle synergy between the same tasks may be beneficial to improve the detection accuracy over long time ranges. However, the conventional muscle synergy extraction methods, such as non-negative matrix factorization (NMF) and principal component analysis (PCA) have some limitations in the field of motor intention detection, especially in the continuous estimation of upper limb joint angles.

METHODS: In this study, we proposed a reliable multivariate curve-resolved-alternating least squares (MCR-ALS) muscle synergy extraction method combined with long-short term memory neural network (LSTM) to estimate continuous elbow joint motion by using the sEMG datasets from different subjects and different days. The pre-processed sEMG signals were then decomposed into muscle synergies by MCR-ALS, NMF and PCA methods, and the decomposed muscle activation matrices were used as sEMG features. The sEMG features and elbow joint angular signals were input to LSTM to establish a neural network model. Finally, the established neural network models were tested by using sEMG dataset from different subjects and different days, and the detection accuracy was measured by correlation coefficient.

RESULTS: The detection accuracy of elbow joint angle was more than 85% by using the proposed method. This result was significantly higher than the detection accuracies obtained by using NMF and PCA methods. The results showed that the proposed method can improve the accuracy of motor intention detection results from different subjects and different acquisition timepoints.

DISCUSSION: This study successfully improves the robustness of sEMG signals in neural network applications using an innovative muscle synergy extraction method. It contributes to the application of human physiological signals in human-machine interaction.}, } @article {pmid37333922, year = {2023}, author = {Vaccarino, AL and Black, SE and Gilbert Evans, S and Frey, BN and Javadi, M and Kennedy, SH and Lam, B and Lam, RW and Lasalandra, B and Martens, E and Masellis, M and Milev, R and Mitchell, S and Munoz, DP and Sparks, A and Swartz, RH and Tan, B and Uher, R and Evans, KR}, title = {Rasch analyses of the Quick Inventory of Depressive Symptomatology Self-Report in neurodegenerative and major depressive disorders.}, journal = {Frontiers in psychiatry}, volume = {14}, number = {}, pages = {1154519}, pmid = {37333922}, issn = {1664-0640}, abstract = {BACKGROUND: Symptoms of depression are present in neurodegenerative disorders (ND). It is important that depression-related symptoms be adequately screened and monitored in persons living with ND. The Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR) is a widely-used self-report measure to assess and monitor depressive severity across different patient populations. However, the measurement properties of the QIDS-SR have not been assessed in ND.

AIM: To use Rasch Measurement Theory to assess the measurement properties of the Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR) in ND and in comparison to major depressive disorder (MDD).

METHODS: De-identified data from the Ontario Neurodegenerative Disease Research Initiative (NCT04104373) and Canadian Biomarker Integration Network in Depression (NCT01655706) were used in the analyses. Five hundred and twenty participants with ND (Alzheimer's disease or mild cognitive impairment, amyotrophic lateral sclerosis, cerebrovascular disease, frontotemporal dementia and Parkinson's disease) and 117 participants with major depressive disorder (MDD) were administered the QIDS-SR. Rasch Measurement Theory was used to assess measurement properties of the QIDS-SR, including unidimensionality and item-level fit, category ordering, item targeting, person separation index and reliability and differential item functioning.

RESULTS: The QIDS-SR fit well to the Rasch model in ND and MDD, including unidimensionality, satisfactory category ordering and goodness-of-fit. Item-person measures (Wright maps) showed gaps in item difficulties, suggesting poor precision for persons falling between those severity levels. Differences between mean person and item measures in the ND cohort logits suggest that QIDS-SR items target more severe depression than experienced by the ND cohort. Some items showed differential item functioning between cohorts.

CONCLUSION: The present study supports the use of the QIDS-SR in MDD and suggest that the QIDS-SR can be also used to screen for depressive symptoms in persons with ND. However, gaps in item targeting were noted that suggests that the QIDS-SR cannot differentiate participants falling within certain severity levels. Future studies would benefit from examination in a more severely depressed ND cohort, including those with diagnosed clinical depression.}, } @article {pmid37333274, year = {2023}, author = {Tseng, YJ and Malik, I and Deng, X and Krans, A and Jansen-West, K and Tank, EMH and Gomez, NB and Sher, R and Petrucelli, L and Barmada, SJ and Todd, PK}, title = {Ribosomal quality control factors inhibit repeat-associated non-AUG translation from GC-rich repeats.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {37333274}, issn = {2692-8205}, support = {RF1 AG062171/AG/NIA NIH HHS/United States ; R01 NS086810/NS/NINDS NIH HHS/United States ; P50 HD104463/HD/NICHD NIH HHS/United States ; RF1 AG062077/AG/NIA NIH HHS/United States ; I01 BX004842/BX/BLRD VA/United States ; P01 NS084974/NS/NINDS NIH HHS/United States ; P30 AG072931/AG/NIA NIH HHS/United States ; R01 NS099280/NS/NINDS NIH HHS/United States ; R01 NS113943/NS/NINDS NIH HHS/United States ; R35 NS097273/NS/NINDS NIH HHS/United States ; R01 NS097542/NS/NINDS NIH HHS/United States ; R56 NS128110/NS/NINDS NIH HHS/United States ; }, abstract = {A GGGGCC (G4C2) hexanucleotide repeat expansion in C9ORF72 causes amyotrophic lateral sclerosis and frontotemporal dementia (C9ALS/FTD), while a CGG trinucleotide repeat expansion in FMR1 leads to the neurodegenerative disorder Fragile X-associated tremor/ataxia syndrome (FXTAS). These GC-rich repeats form RNA secondary structures that support repeat-associated non-AUG (RAN) translation of toxic proteins that contribute to disease pathogenesis. Here we assessed whether these same repeats might trigger stalling and interfere with translational elongation. We find that depletion of ribosome-associated quality control (RQC) factors NEMF, LTN1, and ANKZF1 markedly boost RAN translation product accumulation from both G4C2 and CGG repeats while overexpression of these factors reduces RAN production in both reporter cell lines and C9ALS/FTD patient iPSC-derived neurons. We also detected partially made products from both G4C2 and CGG repeats whose abundance increased with RQC factor depletion. Repeat RNA sequence, rather than amino acid content, is central to the impact of RQC factor depletion on RAN translation - suggesting a role for RNA secondary structure in these processes. Together, these findings suggest that ribosomal stalling and RQC pathway activation during RAN translation elongation inhibits the generation of toxic RAN products. We propose augmenting RQC activity as a therapeutic strategy in GC-rich repeat expansion disorders.}, } @article {pmid37333227, year = {2023}, author = {Krebs, AS and Liu, HF and Zhou, Y and Rey, JS and Levintov, L and Shen, J and Howe, A and Perilla, JR and Bartesaghi, A and Zhang, P}, title = {Molecular architecture and conservation of an immature human endogenous retrovirus.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {37333227}, issn = {2692-8205}, support = {/WT_/Wellcome Trust/United Kingdom ; R01 AI157843/AI/NIAID NIH HHS/United States ; R01 GM141223/GM/NIGMS NIH HHS/United States ; }, abstract = {A significant part of the human genome consists of endogenous retroviruses sequences. Human endogenous retrovirus K (HERV-K) is the most recently acquired endogenous retrovirus, is activated and expressed in many cancers and amyotrophic lateral sclerosis and possibly contributes to the aging process. To understand the molecular architecture of endogenous retroviruses, we determined the structure of immature HERV-K from native virus-like particles (VLPs) using cryo-electron tomography and subtomogram averaging (cryoET STA). The HERV-K VLPs show a greater distance between the viral membrane and immature capsid lattice, correlating with the presence of additional peptides, SP1 and p15, between the capsid (CA) and matrix (MA) proteins compared to the other retroviruses. The resulting cryoET STA map of the immature HERV-K capsid at 3.2 Å resolution shows a hexamer unit oligomerized through a 6-helix bundle which is further stabilized by a small molecule in the same way as the IP6 in immature HIV-1 capsid. The HERV-K immature CA hexamer assembles into the immature lattice via highly conserved dimmer and trimer interfaces, whose interactions were further detailed through all-atom molecular dynamics simulations and supported by mutational studies. A large conformational change mediated by the flexible linker between the N-terminal and the C-terminal domains of CA occurs between the immature and the mature HERV-K capsid protein, analogous to HIV-1. Comparison between HERV-K and other retroviral immature capsid structures reveals a highly conserved mechanism for the assembly and maturation of retroviruses across genera and evolutionary time.}, } @article {pmid37333144, year = {2023}, author = {Nelson, AT and Cicardi, ME and Markandaiah, SS and Han, J and Philp, N and Welebob, E and Haeusler, AR and Pasinelli, P and Manfredi, G and Kawamata, H and Trotti, D}, title = {Glucose Hypometabolism Prompts RAN Translation and Exacerbates C9orf72-related ALS/FTD Phenotypes.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {37333144}, issn = {2692-8205}, support = {RF1 NS114128/NS/NINDS NIH HHS/United States ; R21 NS090912/NS/NINDS NIH HHS/United States ; R01 NS109150/NS/NINDS NIH HHS/United States ; R35 NS122209/NS/NINDS NIH HHS/United States ; F31 NS118838/NS/NINDS NIH HHS/United States ; RF1 AG057882/AG/NIA NIH HHS/United States ; }, abstract = {The most prevalent genetic cause of both amyotrophic lateral sclerosis and frontotemporal dementia is a (GGGGCC)n nucleotide repeat expansion (NRE) occurring in the first intron of the C9orf72 gene (C9). Brain glucose hypometabolism is consistently observed in C9-NRE carriers, even at pre-symptomatic stages, although its potential role in disease pathogenesis is unknown. Here, we identified alterations in glucose metabolic pathways and ATP levels in the brain of asymptomatic C9-BAC mice. We found that, through activation of the GCN2 kinase, glucose hypometabolism drives the production of dipeptide repeat proteins (DPRs), impairs the survival of C9 patient-derived neurons, and triggers motor dysfunction in C9-BAC mice. We also found that one of the arginine-rich DPRs (PR) can directly contribute to glucose metabolism and metabolic stress. These findings provide a mechanistic link between energy imbalances and C9-ALS/FTD pathogenesis and support a feedforward loop model that opens several opportunities for therapeutic intervention.}, } @article {pmid37333094, year = {2023}, author = {Guise, AJ and Misal, SA and Carson, R and Boekweg, H and Watt, DV and Truong, T and Liang, Y and Chu, JH and Welsh, NC and Gagnon, J and Payne, SH and Plowey, ED and Kelly, RT}, title = {TDP-43-stratified single-cell proteomic profiling of postmortem human spinal motor neurons reveals protein dynamics in amyotrophic lateral sclerosis.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {37333094}, issn = {2692-8205}, support = {R01 GM138931/GM/NIGMS NIH HHS/United States ; R33 CA225248/CA/NCI NIH HHS/United States ; }, abstract = {Unbiased proteomics has been employed to interrogate central nervous system (CNS) tissues (brain, spinal cord) and fluid matrices (CSF, plasma) from amyotrophic lateral sclerosis (ALS) patients; yet, a limitation of conventional bulk tissue studies is that motor neuron (MN) proteome signals may be confounded by admixed non-MN proteins. Recent advances in trace sample proteomics have enabled quantitative protein abundance datasets from single human MNs (Cong et al., 2020b). In this study, we leveraged laser capture microdissection (LCM) and nanoPOTS (Zhu et al., 2018c) single-cell mass spectrometry (MS)-based proteomics to query changes in protein expression in single MNs from postmortem ALS and control donor spinal cord tissues, leading to the identification of 2515 proteins across MNs samples (>900 per single MN) and quantitative comparison of 1870 proteins between disease groups. Furthermore, we studied the impact of enriching/stratifying MN proteome samples based on the presence and extent of immunoreactive, cytoplasmic TDP-43 inclusions, allowing identification of 3368 proteins across MNs samples and profiling of 2238 proteins across TDP-43 strata. We found extensive overlap in differential protein abundance profiles between MNs with or without obvious TDP-43 cytoplasmic inclusions that together point to early and sustained dysregulation of oxidative phosphorylation, mRNA splicing and translation, and retromer-mediated vesicular transport in ALS. Our data are the first unbiased quantification of single MN protein abundance changes associated with TDP-43 proteinopathy and begin to demonstrate the utility of pathology-stratified trace sample proteomics for understanding single-cell protein abundance changes in human neurologic diseases.}, } @article {pmid37333039, year = {2023}, author = {Mann, RH}, title = {Impaired Thiamine Metabolism in Amyotrophic Lateral Sclerosis and Its Potential Treatment With Benfotiamine: A Case Report and a Review of the Literature.}, journal = {Cureus}, volume = {15}, number = {6}, pages = {e40511}, pmid = {37333039}, issn = {2168-8184}, abstract = {Homogenates of brain tissue from the frontal cortex at autopsy in patients with amyotrophic lateral sclerosis (ALS) showed dramatically reduced levels of the enzyme thiamine pyrophosphatase (TPPase), the enzyme responsible for the conversion of thiamine pyrophosphate (TPP) to thiamine monophosphate (TMP). Additionally, free thiamine (vitamin B1) and TMP levels have been shown to be significantly reduced in the plasma and cerebral spinal fluid (CSF) of patients with ALS. These findings suggest that there is impaired thiamine metabolism in patients with ALS. Impaired thiamine metabolism decreases adenosine triphosphate (ATP) production and is a well-established cause of neurodegeneration. Decreased levels of TPPase, resulting in decreased levels of TMP in the cells of the frontal cortex, might account for the focal neurodegenerative changes observed in motor neurons in ALS. Benfotiamine, a safe, lipid-soluble, highly absorbable thiamine analogue, significantly raises free thiamine, TMP, and TPP levels in the blood. A case in which benfotiamine may have positively impacted the symptoms of a patient with ALS is presented. The use of benfotiamine in patients with ALS appears to be a promising therapeutic option. Considering the severity and the lack of satisfactory treatment options associated with this disease, more research on the effects of benfotiamine on the course of ALS is urgently needed.}, } @article {pmid37786905, year = {2021}, author = {Huang, ZQ and Ba, ZS and Huang, NQ and Li, YY and Luo, Y}, title = {Aberrant TDP-43 phosphorylation: a key wind gap from TDP-43 to TDP-43 proteinopathy.}, journal = {Ibrain}, volume = {7}, number = {2}, pages = {119-131}, pmid = {37786905}, issn = {2769-2795}, abstract = {TDP-43 proteinopathy is a kind of neurodegenerative diseases related to the TAR DNA-binding protein of 43-kDa molecular weight (TDP-43). The typical neurodegenerative diseases include amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration (FTLD), Alzheimer's disease (AD), Parkinson's disease (PD) and so on. As the disease process cannot be blocked or slowed down, these patients have poor quality of life and poor prognosis, and bring a huge burden to the family and society. So far, the specific pathogenesis of TDP-43 proteinopathy is not clear, and there is no effective preventive measure and treatment program for this kind of disease. TDP-43 plays an important role in triggering or promoting the occurrence and progression of TDP-43 proteinopathy. The hyperphosphorylation of TDP-43 is undoubtedly an important factor in triggering or promoting the process of TDP-43 proteinopathy. Hyperphosphorylation of TDP-43 can inhibit the degradation of TDP-43, aggravate the aggregation of TDP-43 protein, increase the wrong localization of TDP-43 in cells, and enhance the cytotoxicity of TDP-43. More and more evidences show that the hyperphosphorylation of TDP-43 plays an important role in the pathogenesis of TDP-43 proteinopathy. Inhibition of TDP-43 hyperphosphorylation may be one of the important strategies for the treatment of TDP-43 proteinopathy. Therefore, this article reviews the role of TDP-43 phosphorylation in TDP-43 proteinopathy and the related mechanisms.}, } @article {pmid37427003, year = {2021}, author = {Horowitz, AJ and Guger, C and Korostenskaja, M}, title = {What Internal Variables Affect Sensorimotor Rhythm Brain-Computer Interface (SMR-BCI) Performance?.}, journal = {HCA healthcare journal of medicine}, volume = {2}, number = {3}, pages = {163-179}, pmid = {37427003}, issn = {2689-0216}, abstract = {Description In this review article, we aimed to create a summary of the effects of internal variables on the performance of sensorimotor rhythm-based brain computer interfaces (SMR-BCIs). SMR-BCIs can be potentially used for interfacing between the brain and devices, bypassing usual central nervous system output, such as muscle activity. The careful consideration of internal factors, affecting SMR-BCI performance, can maximize BCI application in both healthy and disabled people. Internal variables may be generalized as descriptors of the processes mainly dependent on the BCI user and/or originating within the user. The current review aimed to critically evaluate and summarize the currently accumulated body of knowledge regarding the effect of internal variables on SMR-BCI performance. The examples of such internal variables include motor imagery, hand coordination, attention, motivation, quality of life, mood and neurophysiological signals other than SMR. We will conclude our review with the discussion about the future developments regarding the research on the effects of internal variables on SMR-BCI performance. The end-goal of this review paper is to provide current BCI users and researchers with the reference guide that can help them optimize the SMR-BCI performance by accounting for possible influences of various internal factors.}, } @article {pmid37366377, year = {2021}, author = {Borgese, N and Navone, F and Nukina, N and Yamanaka, T}, title = {Mutant VAPB: Culprit or Innocent Bystander of Amyotrophic Lateral Sclerosis?.}, journal = {Contact (Thousand Oaks (Ventura County, Calif.))}, volume = {4}, number = {}, pages = {25152564211022515}, pmid = {37366377}, issn = {2515-2564}, abstract = {Nearly twenty years ago a mutation in the VAPB gene, resulting in a proline to serine substitution (p.P56S), was identified as the cause of a rare, slowly progressing, familial form of the motor neuron degenerative disease Amyotrophic Lateral Sclerosis (ALS). Since then, progress in unravelling the mechanistic basis of this mutation has proceeded in parallel with research on the VAP proteins and on their role in establishing membrane contact sites between the ER and other organelles. Analysis of the literature on cellular and animal models reviewed here supports the conclusion that P56S-VAPB, which is aggregation-prone, non-functional and unstable, is expressed at levels that are insufficient to support toxic gain-of-function or dominant negative effects within motor neurons. Instead, insufficient levels of the product of the single wild-type allele appear to be required for pathological effects, and may be the main driver of the disease. In light of the multiple interactions of the VAP proteins, we address the consequences of specific VAPB depletion and highlight various affected processes that could contribute to motor neuron degeneration. In the future, distinction of specific roles of each of the two VAP paralogues should help to further elucidate the basis of p.P56S familial ALS, as well as of other more common forms of the disease.}, } @article {pmid37387779, year = {2021}, author = {Huang, H and Chen, L and Chopp, M and Young, W and Robert Bach, J and He, X and Sarnowaska, A and Xue, M and Chunhua Zhao, R and Shetty, A and Siniscalco, D and Guo, X and Khoshnevisan, A and Hawamdeh, Z}, title = {The 2020 Yearbook of Neurorestoratology.}, journal = {Journal of neurorestoratology}, volume = {9}, number = {1}, pages = {1-12}, pmid = {37387779}, issn = {2324-2426}, abstract = {COVID-19 has been an emerging and rapidly evolving risk to people of the world in 2020. Facing this dangerous situation, many colleagues in Neurorestoratology did their best to avoid infection if themselves and their patients, and continued their work in the research areas described in the 2020 Yearbook of Neurorestoratology. Neurorestorative achievements and progress during 2020 includes recent findings on the pathogenesis of neurological diseases, neurorestorative mechanisms and clinical therapeutic achievements. Therapeutic progress during this year included advances in cell therapies, neurostimulation/neuromodulation, brain-computer interface (BCI), and pharmaceutical neurorestorative therapies, which improved neurological functions and quality of life for patients. Four clinical guidelines or standards of Neurorestoratology were published in 2020. Milestone examples include: 1) a multicenter randomized, double-blind, placebo-controlled study of olfactory ensheathing cell treatment of chronic stroke showed functional improvements; 2) patients after transhumeral amputation experienced increased sensory acuity and had improved effectiveness in work and other activities of daily life using a prosthesis; 3) a patient with amyotrophic lateral sclerosis used a steady-state visual evoked potential (SSVEP)-based BCI to achieve accurate and speedy computer input; 4) a patient with complete chronic spinal cord injury recovered both motor function and touch sensation with a BCI and restored ability to detect objects by touch and several sensorimotor functions. We hope these achievements motivate and encourage other scientists and physicians to increase neurorestorative research and its therapeutic applications.}, } @article {pmid37465403, year = {2020}, author = {Au, C and Myatt, T}, title = {Loose PEG Tube Leading to Peristomal Leakage and Peritonitis, a Case Report.}, journal = {Journal of education & teaching in emergency medicine}, volume = {5}, number = {2}, pages = {V7-V10}, pmid = {37465403}, issn = {2474-1949}, abstract = {UNLABELLED: We present the case of a 37-year-old male with history of amyotrophic lateral sclerosis (ALS) and recent percutaneous endoscopic gastrostomy (PEG) tube placement presented with abdominal pain, nausea, vomiting, abdominal distention, tenderness and guarding. Given the concern for peritonitis, upright/decubitus chest X-ray was obtained and showed bilateral free peritoneal air suggesting possible perforation or peristomal leakage after PEG tube placement. While PEG complication rates are relatively low, clinicians should consider them and remember that chest X-ray can be a very efficient and accurate method of evaluation for possible gastrointestinal perforation, especially in acute emergencies.

TOPICS: Abdominal/gastrointestinal, peritonitis, perforation, surgical complication.}, } @article {pmid37577056, year = {2020}, author = {Fogarty, MJ and Brown, AD and Sieck, GC}, title = {MOTOR NEURON LOSS IN AGING AND AMYOTROPHIC LATERAL SCLEROSIS: DIFFERENT FUSE LENGTHS, SAME EXPLOSION.}, journal = {Physiological mini-reviews}, volume = {13}, number = {1}, pages = {1-11}, pmid = {37577056}, issn = {1669-5410}, support = {R01 AG044615/AG/NIA NIH HHS/United States ; R01 AG057052/AG/NIA NIH HHS/United States ; R01 HL146114/HL/NHLBI NIH HHS/United States ; T32 HL105355/HL/NHLBI NIH HHS/United States ; }, abstract = {Advanced age and amyotrophic lateral sclerosis (ALS) are both associated with a loss of motor neurons resulting in muscle fiber atrophy and muscle weakness. Aging associated muscle fiber atrophy and weakening is termed sarcopenia, but the association with motor neuron loss is not as clearly established as in ALS, probably related to the prolonged time course of aging-related changes. Although aging and ALS effects on limb muscle strength and neuromotor performance are serious, such effects on the diaphragm muscle can be life threatening. Converging evidence indicates that larger phrenic motor neurons, innervating more fatigable type IIx and/or IIb diaphragm muscle fibers (fast fatigue intermediate, FInt and fast fatigable, FF motor units) are more susceptible to degeneration with both aging and ALS compared to smaller phrenic motor neurons innervating type I and IIa diaphragm muscle fibers (slow and fast fatigue resistant motor units, respectively). The etiology of ALS and age-related loss of motor neurons appears to involve mitochondrial function and neuroinflammation, both chronic and acute exacerbation. How mitochondrial dysfunction, neuroinflammation and motor neuron size intersect is the focus of continuing investigation.}, } @article {pmid37333000, year = {2023}, author = {Boostani, R and Olfati, N and Shamshiri, H and Salimi, Z and Fatehi, F and Hedjazi, SA and Fakharian, A and Ghasemi, M and Okhovat, AA and Basiri, K and Haghi Ashtiani, B and Ansari, B and Raissi, GR and Khatoonabadi, SA and Sarraf, P and Movahed, S and Panahi, A and Ziaadini, B and Yazdchi, M and Bakhtiyari, J and Nafissi, S}, title = {Iranian clinical practice guideline for amyotrophic lateral sclerosis.}, journal = {Frontiers in neurology}, volume = {14}, number = {}, pages = {1154579}, pmid = {37333000}, issn = {1664-2295}, abstract = {Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegeneration involving motor neurons. The 3-5 years that patients have to live is marked by day-to-day loss of motor and sometimes cognitive abilities. Enormous amounts of healthcare services and resources are necessary to support patients and their caregivers during this relatively short but burdensome journey. Organization and management of these resources need to best meet patients' expectations and health system efficiency mandates. This can only occur in the setting of multidisciplinary ALS clinics which are known as the gold standard of ALS care worldwide. To introduce this standard to the care of Iranian ALS patients, which is an inevitable quality milestone, a national ALS clinical practice guideline is the necessary first step. The National ALS guideline will serve as the knowledge base for the development of local clinical pathways to guide patient journeys in multidisciplinary ALS clinics. To this end, we gathered a team of national neuromuscular experts as well as experts in related specialties necessary for delivering multidisciplinary care to ALS patients to develop the Iranian ALS clinical practice guideline. Clinical questions were prepared in the Patient, Intervention, Comparison, and Outcome (PICO) format to serve as a guide for the literature search. Considering the lack of adequate national/local studies at this time, a consensus-based approach was taken to evaluate the quality of the retrieved evidence and summarize recommendations.}, } @article {pmid37332910, year = {2023}, author = {Rather, MA and Khan, A and Wang, L and Jahan, S and Rehman, MU and Makeen, HA and Mohan, S}, title = {TRP channels: Role in neurodegenerative diseases and therapeutic targets.}, journal = {Heliyon}, volume = {9}, number = {6}, pages = {e16910}, pmid = {37332910}, issn = {2405-8440}, abstract = {TRP (Transient receptor potential) channels are integral membrane proteins consisting of a superfamily of cation channels that allow permeability of both monovalent and divalent cations. TRP channels are subdivided into six subfamilies: TRPC, TRPV, TRPM, TRPP, TRPML, and TRPA, and are expressed in almost every cell and tissue. TRPs play an instrumental role in the regulation of various physiological processes. TRP channels are extensively represented in brain tissues and are present in both prokaryotes and eukaryotes, exhibiting responses to several mechanisms, including physical, chemical, and thermal stimuli. TRP channels are involved in the perturbation of Ca[2+] homeostasis in intracellular calcium stores, both in neuronal and non-neuronal cells, and its discrepancy leads to several neuronal disorders such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and Amyotrophic lateral sclerosis (ALS). TRPs participate in neurite outgrowth, receptor signaling, and excitotoxic cell death in the central nervous system. Understanding the mechanism of TRP channels in neurodegenerative diseases may extend to developing novel therapies. Thus, this review articulates TRP channels' physiological and pathological role in exploring new therapeutic interventions in neurodegenerative diseases.}, } @article {pmid37332610, year = {2023}, author = {Ghaffari, LT and Trotti, D and Haeusler, AR}, title = {Differential response of C9orf72 transcripts following neuronal depolarization.}, journal = {iScience}, volume = {26}, number = {6}, pages = {106959}, pmid = {37332610}, issn = {2589-0042}, support = {R21 NS090912/NS/NINDS NIH HHS/United States ; R21 NS116761/NS/NINDS NIH HHS/United States ; RF1 AG057882/AG/NIA NIH HHS/United States ; RF1 NS114128/NS/NINDS NIH HHS/United States ; }, abstract = {The (G4C2)n nucleotide repeat expansion (NRE) mutation in C9orf72 is the most common genetic cause of ALS and FTD. The biological functions of C9orf72 are becoming understood, but it is unclear if this gene is regulated in a neural-specific manner. Neuronal activity is a crucial modifier of biological processes in health and neurodegenerative disease contexts. Here, we show that prolonged membrane depolarization in healthy human iPSC-cortical neurons leads to a significant downregulation of a transcript variant 3 (V3) of C9orf72, with a concomitant increase in variant 2 (V2), which leads to total C9orf72 RNA transcript levels remaining unchanged. However, the same response is not observed in cortical neurons derived from patients with the C9-NRE mutation. These findings reveal the impact of depolarization on C9orf72 transcripts, and how this response diverges in C9-NRE-carriers, which may have important implications in the underlying unique clinical associations of C9-NRE transcripts and disease pathogenesis.}, } @article {pmid37332605, year = {2023}, author = {Miyagi, T and Ueda, K and Sugimoto, M and Yagi, T and Ito, D and Yamazaki, R and Narumi, S and Hayamizu, Y and Uji-I, H and Kuroda, M and Kanekura, K}, title = {Differential toxicity and localization of arginine-rich C9ORF72 dipeptide repeat proteins depend on de-clustering of positive charges.}, journal = {iScience}, volume = {26}, number = {6}, pages = {106957}, pmid = {37332605}, issn = {2589-0042}, abstract = {Arginine-rich dipeptide repeat proteins (R-DPRs), poly(PR) and poly(GR), translated from the hexanucleotide repeat expansion in the amyotrophic lateral sclerosis (ALS)-causative C9ORF72 gene, contribute significantly to pathogenesis of ALS. Although both R-DPRs share many similarities, there are critical differences in their subcellular localization, phase separation, and toxicity mechanisms. We analyzed localization, protein-protein interactions, and phase separation of R-DPR variants and found that sufficient segregation of arginine charges is necessary for nucleolar distribution. Proline not only efficiently separated the charges, but also allowed for weak, but highly multivalent binding. In contrast, because of its high flexibility, glycine cannot fully separate the charges, and poly(GR) behaves similarly to the contiguous arginines, being trapped in the cytoplasm. We conclude that the amino acid that spaces the arginine charges determines the strength and multivalency of the binding, leading to differences in localization and toxicity mechanisms.}, } @article {pmid37331748, year = {2023}, author = {Ma, Y and Ye, S and Zhao, D and Liu, X and Cao, L and Zhou, H and Zuo, G and Shi, C}, title = {Using different matrix factorization approaches to identify muscle synergy in stroke survivors.}, journal = {Medical engineering & physics}, volume = {117}, number = {}, pages = {103993}, doi = {10.1016/j.medengphy.2023.103993}, pmid = {37331748}, issn = {1873-4030}, mesh = {Humans ; *Muscle, Skeletal/physiology ; Electromyography ; *Stroke/complications ; Algorithms ; }, abstract = {Over the past several decades, many scholars have investigated muscle synergy as a promising tool for evaluating motor function. However, it is challenging to obtain favorable robustness using the general muscle synergy identification algorithms, namely non-negative matrix factorization (NMF), independent component analysis (ICA), and factor analysis (FA). Some scholars have proposed improved muscle synergy identification algorithms to overcome the shortcomings of these approaches, such as singular value decomposition NMF (SVD-NMF), sparse NMF (S-NMF), and multivariate curve resolution-alternating least squares (MCR-ALS). However, performance comparisons of these algorithms are seldom conducted. In this study, experimental electromyography (EMG) data collected from healthy individuals and stroke survivors were applied to assess the repeatability and intra-subject consistency of NMF, SVD-NMF, S-NMF, ICA, FA, and MCR-ALS. MCR-ALS presented higher repeatability and intra-subject consistencies than the other algorithms. More synergies and lower intra-subject consistencies were observed in stroke survivors than in healthy individuals. Thus, MCR-ALS is considered a favorable muscle synergy identification algorithm for patients with neural system disorders.}, } @article {pmid37331636, year = {2023}, author = {Zhang, H and Qi, G and Wang, K and Yang, J and Shen, Y and Yang, X and Chen, X and Yao, X and Gu, X and Qi, L and Zhou, C and Sun, H}, title = {Oxidative stress: Roles in skeletal muscle atrophy.}, journal = {Biochemical pharmacology}, volume = {214}, number = {}, pages = {115664}, doi = {10.1016/j.bcp.2023.115664}, pmid = {37331636}, issn = {1873-2968}, mesh = {Humans ; *Muscular Atrophy/metabolism ; Oxidative Stress ; Muscle, Skeletal/metabolism ; *Sarcopenia/drug therapy/metabolism/pathology ; Antioxidants/metabolism ; Chronic Disease ; }, abstract = {Oxidative stress, inflammation, mitochondrial dysfunction, reduced protein synthesis, and increased proteolysis are all critical factors in the process of muscle atrophy. In particular, oxidative stress is the key factor that triggers skeletal muscle atrophy. It is activated in the early stages of muscle atrophy and can be regulated by various factors. The mechanisms of oxidative stress in the development of muscle atrophy have not been completely elucidated. This review provides an overview of the sources of oxidative stress in skeletal muscle and the correlation of oxidative stress with inflammation, mitochondrial dysfunction, autophagy, protein synthesis, proteolysis, and muscle regeneration in muscle atrophy. Additionally, the role of oxidative stress in skeletal muscle atrophy caused by several pathological conditions, including denervation, unloading, chronic inflammatory diseases (diabetes mellitus, chronic kidney disease, chronic heart failure, and chronic obstructive pulmonary disease), sarcopenia, hereditary neuromuscular diseases (spinal muscular atrophy, amyotrophic lateral sclerosis, and Duchenne muscular dystrophy), and cancer cachexia, have been discussed. Finally, this review proposes the alleviation oxidative stress using antioxidants, Chinese herbal extracts, stem cell and extracellular vesicles as a promising therapeutic strategy for muscle atrophy. This review will aid in the development of novel therapeutic strategies and drugs for muscle atrophy.}, } @article {pmid37328865, year = {2023}, author = {Wainberg, M and Andrews, SJ and Tripathy, SJ}, title = {Shared genetic risk loci between Alzheimer's disease and related dementias, Parkinson's disease, and amyotrophic lateral sclerosis.}, journal = {Alzheimer's research & therapy}, volume = {15}, number = {1}, pages = {113}, pmid = {37328865}, issn = {1758-9193}, support = {R00 AG070109/AG/NIA NIH HHS/United States ; }, mesh = {Humans ; *Alzheimer Disease/genetics ; *Parkinson Disease/genetics ; *Amyotrophic Lateral Sclerosis/genetics ; Genome-Wide Association Study ; Genetic Predisposition to Disease/genetics ; *Neurodegenerative Diseases/genetics ; Polymorphism, Single Nucleotide/genetics ; }, abstract = {BACKGROUND: Genome-wide association studies (GWAS) have indicated moderate genetic overlap between Alzheimer's disease (AD) and related dementias (ADRD), Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS), neurodegenerative disorders traditionally considered etiologically distinct. However, the specific genetic variants and loci underlying this overlap remain almost entirely unknown.

METHODS: We leveraged state-of-the-art GWAS for ADRD, PD, and ALS. For each pair of disorders, we examined each of the GWAS hits for one disorder and tested whether they were also significant for the other disorder, applying Bonferroni correction for the number of variants tested. This approach rigorously controls the family-wise error rate for both disorders, analogously to genome-wide significance.

RESULTS: Eleven loci with GWAS hits for one disorder were also associated with one or both of the other disorders: one with all three disorders (the MAPT/KANSL1 locus), five with ADRD and PD (near LCORL, CLU, SETD1A/KAT8, WWOX, and GRN), three with ADRD and ALS (near GPX3, HS3ST5/HDAC2/MARCKS, and TSPOAP1), and two with PD and ALS (near GAK/TMEM175 and NEK1). Two of these loci (LCORL and NEK1) were associated with an increased risk of one disorder but decreased risk of another. Colocalization analysis supported a shared causal variant between ADRD and PD at the CLU, WWOX, and LCORL loci, between ADRD and ALS at the TSPOAP1 locus, and between PD and ALS at the NEK1 and GAK/TMEM175 loci. To address the concern that ADRD is an imperfect proxy for AD and that the ADRD and PD GWAS have overlapping participants (nearly all of which are from the UK Biobank), we confirmed that all our ADRD associations had nearly identical odds ratios in an AD GWAS that excluded the UK Biobank, and all but one remained nominally significant (p < 0.05) for AD.

CONCLUSIONS: In one of the most comprehensive investigations to date of pleiotropy between neurodegenerative disorders, we identify eleven genetic risk loci shared among ADRD, PD, and ALS. These loci support lysosomal/autophagic dysfunction (GAK/TMEM175, GRN, KANSL1), neuroinflammation/immunity (TSPOAP1), oxidative stress (GPX3, KANSL1), and the DNA damage response (NEK1) as transdiagnostic processes underlying multiple neurodegenerative disorders.}, } @article {pmid37328685, year = {2023}, author = {Pisharady, PK and Eberly, LE and Adanyeguh, IM and Manousakis, G and Guliani, G and Walk, D and Lenglet, C}, title = {Multimodal MRI improves diagnostic accuracy and sensitivity to longitudinal change in amyotrophic lateral sclerosis.}, journal = {Communications medicine}, volume = {3}, number = {1}, pages = {84}, pmid = {37328685}, issn = {2730-664X}, support = {P41 EB015894/EB/NIBIB NIH HHS/United States ; }, abstract = {BACKGROUND: Recent advances in MRI acquisitions and image analysis have increased the utility of neuroimaging in understanding disease-related changes. In this work, we aim to demonstrate increased sensitivity to disease progression as well as improved diagnostic accuracy in Amyotrophic lateral sclerosis (ALS) with multimodal MRI of the brain and cervical spinal cord.

METHODS: We acquired diffusion MRI data from the brain and cervical cord, and T1 data from the brain, of 20 participants with ALS and 20 healthy control participants. Ten ALS and 14 control participants, and 11 ALS and 13 control participants were re-scanned at 6-month and 12-month follow-ups respectively. We estimated cross-sectional differences and longitudinal changes in diffusion metrics, cortical thickness, and fixel-based microstructure measures, i.e. fiber density and fiber cross-section.

RESULTS: We demonstrate improved disease diagnostic accuracy and sensitivity through multimodal analysis of brain and spinal cord metrics. The brain metrics also distinguished lower motor neuron-predominant ALS participants from control participants. Fiber density and cross-section provided the greatest sensitivity to longitudinal change. We demonstrate evidence of progression in a cohort of 11 participants with slowly progressive ALS, including in participants with very slow change in ALSFRS-R. More importantly, we demonstrate that longitudinal change is detectable at a six-month follow-up visit. We also report correlations between ALSFRS-R and the fiber density and cross-section metrics.

CONCLUSIONS: Our findings suggest that multimodal MRI is useful in improving disease diagnosis, and fixel-based measures may serve as potential biomarkers of disease progression in ALS clinical trials.}, } @article {pmid37328037, year = {2023}, author = {Xu, L and Wang, D and Zhao, L and Yang, Z and Liu, X and Li, X and Yuan, T and Wang, Y and Huang, T and Bian, N and He, Y and Chen, X and Tian, B and Liu, Z and Luo, F and Si, W and Gao, G and Ji, W and Niu, Y and Wei, J}, title = {C9orf72 poly(PR) aggregation in nucleus induces ALS/FTD-related neurodegeneration in cynomolgus monkeys.}, journal = {Neurobiology of disease}, volume = {184}, number = {}, pages = {106197}, doi = {10.1016/j.nbd.2023.106197}, pmid = {37328037}, issn = {1095-953X}, mesh = {Animals ; *Amyotrophic Lateral Sclerosis/metabolism ; C9orf72 Protein/genetics/metabolism ; Dipeptides/genetics ; DNA Repeat Expansion ; *Frontotemporal Dementia/genetics/pathology ; Macaca fascicularis/genetics/metabolism ; Proteins/genetics ; Proteomics ; Disease Models, Animal ; }, abstract = {Poly(PR) is a dipeptide repeat protein comprising proline and arginine residues. It is one of the translational product of expanded G4C2 repeats in the C9orf72 gene, and its accumulation is contributing to the neuropathogenesis of C9orf72-associated amyotrophic lateral sclerosis and/or frontotemporal dementia (C9-ALS/FTD). In this study, we demonstrate that poly(PR) protein alone is sufficient to induce neurodegeneration related to ALS/FTD in cynomolgus monkeys. By delivering poly(PR) via AAV, we observed that the PR proteins were located within the nucleus of infected cells. The expression of (PR)50 protein, consisting of 50 PR repeats, led to increased loss of cortical neurons, cytoplasmic lipofuscin, and gliosis in the brain, as well as demyelination and loss of ChAT positive neurons in the spinal cord of monkeys. While, these pathologies were not observed in monkeys expressing (PR)5, a protein comprising only 5 PR repeats. Furthermore, the (PR)50-expressing monkeys exhibited progressive motor deficits, cognitive impairment, muscle atrophy, and abnormal electromyography (EMG) potentials, which closely resemble clinical symptoms seen in C9-ALS/FTD patients. By longitudinally tracking these monkeys, we found that changes in cystatin C and chitinase-1 (CHIT1) levels in the cerebrospinal fluid (CSF) corresponded to the phenotypic progression of (PR)50-induced disease. Proteomic analysis revealed that the major clusters of dysregulated proteins were nuclear-localized, and downregulation of the MECP2 protein was implicated in the toxic process of poly(PR). This research indicates that poly(PR) expression alone induces neurodegeneration and core phenotypes associated with C9-ALS/FTD in monkeys, which may provide insights into the mechanisms of disease pathogenesis.}, } @article {pmid37327984, year = {2023}, author = {Tzeplaeff, L and Seguin, J and Le Gras, S and Megat, S and Cosquer, B and Plassard, D and Dieterlé, S and Paiva, I and Picchiarelli, G and Decraene, C and Alcala-Vida, R and Cassel, JC and Merienne, K and Dupuis, L and Boutillier, AL}, title = {Mutant FUS induces chromatin reorganization in the hippocampus and alters memory processes.}, journal = {Progress in neurobiology}, volume = {227}, number = {}, pages = {102483}, doi = {10.1016/j.pneurobio.2023.102483}, pmid = {37327984}, issn = {1873-5118}, mesh = {Animals ; Mice ; *Amyotrophic Lateral Sclerosis/genetics ; Chromatin/metabolism ; Epigenesis, Genetic ; *Frontotemporal Dementia/genetics ; Hippocampus/metabolism ; Mutation ; RNA-Binding Protein FUS/genetics/metabolism ; Disease Models, Animal ; }, abstract = {Cytoplasmic mislocalization of the nuclear Fused in Sarcoma (FUS) protein is associated to amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Cytoplasmic FUS accumulation is recapitulated in the frontal cortex and spinal cord of heterozygous Fus[∆NLS/+] mice. Yet, the mechanisms linking FUS mislocalization to hippocampal function and memory formation are still not characterized. Herein, we show that in these mice, the hippocampus paradoxically displays nuclear FUS accumulation. Multi-omic analyses showed that FUS binds to a set of genes characterized by the presence of an ETS/ELK-binding motifs, and involved in RNA metabolism, transcription, ribosome/mitochondria and chromatin organization. Importantly, hippocampal nuclei showed a decompaction of the neuronal chromatin at highly expressed genes and an inappropriate transcriptomic response was observed after spatial training of Fus[∆NLS/+] mice. Furthermore, these mice lacked precision in a hippocampal-dependent spatial memory task and displayed decreased dendritic spine density. These studies shows that mutated FUS affects epigenetic regulation of the chromatin landscape in hippocampal neurons, which could participate in FTD/ALS pathogenic events. These data call for further investigation in the neurological phenotype of FUS-related diseases and open therapeutic strategies towards epigenetic drugs.}, } @article {pmid37327376, year = {2023}, author = {Shefner, JM and Musaro, A and Ngo, ST and Lunetta, C and Steyn, FJ and Robitaille, R and De Carvalho, M and Rutkove, S and Ludolph, AC and Dupuis, L}, title = {Skeletal muscle in amyotrophic lateral sclerosis.}, journal = {Brain : a journal of neurology}, volume = {146}, number = {11}, pages = {4425-4436}, pmid = {37327376}, issn = {1460-2156}, mesh = {Adult ; Humans ; *Amyotrophic Lateral Sclerosis/pathology ; Motor Neurons/pathology ; Muscle, Skeletal/pathology ; Neuromuscular Junction/pathology ; Muscle Weakness ; }, abstract = {Amyotrophic lateral sclerosis (ALS), the major adult-onset motor neuron disease, has been viewed almost exclusively as a disease of upper and lower motor neurons, with muscle changes interpreted as a consequence of the progressive loss of motor neurons and neuromuscular junctions. This has led to the prevailing view that the involvement of muscle in ALS is only secondary to motor neuron loss. Skeletal muscle and motor neurons reciprocally influence their respective development and constitute a single functional unit. In ALS, multiple studies indicate that skeletal muscle dysfunction might contribute to progressive muscle weakness, as well as to the final demise of neuromuscular junctions and motor neurons. Furthermore, skeletal muscle has been shown to participate in disease pathogenesis of several monogenic diseases closely related to ALS. Here, we move the narrative towards a better appreciation of muscle as a contributor of disease in ALS. We review the various potential roles of skeletal muscle cells in ALS, from passive bystanders to active players in ALS pathophysiology. We also compare ALS to other motor neuron diseases and draw perspectives for future research and treatment.}, } @article {pmid37326935, year = {2023}, author = {Cantisani, TA}, title = {Is there a treatment effective and safe for sialorrhea in people with amyotrophic lateral sclerosis (ALS)? Summary of a Cochrane Systematic Review.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {44}, number = {9}, pages = {3083-3085}, pmid = {37326935}, issn = {1590-3478}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy/drug therapy ; *Botulinum Toxins/therapeutic use ; *Sialorrhea/therapy/drug therapy ; Treatment Outcome ; Systematic Reviews as Topic ; }, } @article {pmid37326908, year = {2023}, author = {Zheng, C and Li, W and Ali, T and Peng, Z and Liu, J and Pan, Z and Feng, J and Li, S}, title = {Ibrutinib Delays ALS Installation and Increases Survival of SOD1[G93A] Mice by Modulating PI3K/mTOR/Akt Signaling.}, journal = {Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology}, volume = {18}, number = {3}, pages = {383-396}, pmid = {37326908}, issn = {1557-1904}, support = {NCT03721302//International Cooperation Project（NCT03721302）of Shenzhen Children's Hospital/ ; 2019SHIBS0004//Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions/ ; JCYJ20220530155611026//Basic research of Shenzhen Science and Technology Plan Project（General Program/ ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal multisystem degenerative disorder with minimal available therapeutic. However, some recent studies showed promising results of immunological-based treatment. Here, we aimed to evaluate the efficacy of ibrutinib against ALS-associated abnormalities by targeting inflammation and muscular atrophy. Ibrutinib was administrated orally to SOD1 [G93A] mice from 6 to 19 weeks for prophylactic administration and 13 to 19 weeks for therapeutic administration. Our results demonstrated that ibrutinib treatment significantly delayed ALS-like symptom onset in the SOD1 [G93A] mice, as shown by improved survival time and reduced behavioral impairments. Ibrutinib treatment significantly reduced muscular atrophy by increasing muscle/body weight and decreasing muscular necrosis. The ibrutinib treatment also considerably reduced pro-inflammatory cytokine production, IBA-1, and GFAP expression, possibly mediated by mTOR/Akt/Pi3k signaling in the medulla, motor cortex and spinal cord of the ALS mice. In conclusion, our study demonstrated that ibrutinib could delay ALS onset, increase survival time, and reduce ALS progression by targeting inflammation and muscular atrophy via mTOR/Akt/PI3K modulation.}, } @article {pmid37323141, year = {2023}, author = {Khatoon, S and Kalam, N and Rashid, S and Bano, G}, title = {Effects of gut microbiota on neurodegenerative diseases.}, journal = {Frontiers in aging neuroscience}, volume = {15}, number = {}, pages = {1145241}, pmid = {37323141}, issn = {1663-4365}, abstract = {A progressive degradation of the brain's structure and function, which results in a reduction in cognitive and motor skills, characterizes neurodegenerative diseases (NDs) such as Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD). The morbidity linked to NDs is growing, which poses a severe threat to human being's mental and physical ability to live well. The gut-brain axis (GBA) is now known to have a crucial role in the emergence of NDs. The gut microbiota is a conduit for the GBA, a two-way communication system between the gut and the brain. The myriad microorganisms that make up the gut microbiota can affect brain physiology by transmitting numerous microbial chemicals from the gut to the brain via the GBA or neurological system. The synthesis of neurotransmitters, the immunological response, and the metabolism of lipids and glucose have all been demonstrated to be impacted by alterations in the gut microbiota, such as an imbalance of helpful and harmful bacteria. In order to develop innovative interventions and clinical therapies for NDs, it is crucial to comprehend the participation of the gut microbiota in these conditions. In addition to using antibiotics and other drugs to target particular bacterial species that may be a factor in NDs, this also includes using probiotics and other fecal microbiota transplantation to maintain a healthy gut microbiota. In conclusion, the examination of the GBA can aid in understanding the etiology and development of NDs, which may benefit the improvement of clinical treatments for these disorders and ND interventions. This review indicates existing knowledge about the involvement of microbiota present in the gut in NDs and potential treatment options.}, } @article {pmid37323039, year = {2023}, author = {Baeken, C}, title = {[Haalt rTMS ECT in als behandeling voor depressie? Waarschijnlijk niet in Europa].}, journal = {Tijdschrift voor psychiatrie}, volume = {65}, number = {4}, pages = {219-221}, pmid = {37323039}, issn = {0303-7339}, mesh = {Humans ; *Depressive Disorder, Major ; Transcranial Magnetic Stimulation ; }, } @article {pmid37322338, year = {2023}, author = {Maxwell, MN and Marullo, AL and Slyne, AD and Lucking, EF and O'Halloran, KD}, title = {Ventilatory Effects of Acute Intermittent Hypoxia in Conscious Dystrophic Mice.}, journal = {Advances in experimental medicine and biology}, volume = {1427}, number = {}, pages = {83-88}, doi = {10.1007/978-3-031-32371-3_9}, pmid = {37322338}, issn = {0065-2598}, mesh = {Mice ; Male ; Animals ; Mice, Inbred mdx ; *Hypoxia ; *Respiration ; Hypercapnia ; }, abstract = {Exposure to acute intermittent hypoxia (AIH) elicits a form of respiratory plasticity known as long-term facilitation (LTF). Interest has grown in developing AIH interventions to treat ventilatory insufficiency, with promising results in spinal cord injury and amyotrophic lateral sclerosis. Therapeutic AIH may have application in neuromuscular disorders including muscular dystrophies. We sought to establish hypoxic ventilatory responsiveness and the expression of ventilatory LTF in X-linked muscular dystrophy (mdx) mice.Experiments were performed in 15 male wild-type (BL10) and 15 male mdx mice at 4 months of age. Ventilation was assessed using whole-body plethysmography. Baseline measures of ventilation and metabolism were established. Mice were exposed to 10 successive bouts of hypoxia, each lasting 5 min, interspersed with 5-min bouts of normoxia. Measurements were taken for 60 min following termination of AIH.In mdx mice, ventilation was significantly increased 60 min post-AIH compared to baseline. However, metabolic CO2 production was also increased. Therefore, ventilatory equivalent was unaffected by AIH exposure, i.e., no ventilatory LTF manifestation. In wild-type mice, ventilation and metabolism were not affected by AIH.Eliciting ventilatory LTF is dependent on many factors and may require concomitant isocapnia or hypercapnia during AIH exposures and/or repeated daily AIH exposures, which is worthy of further pursuit.}, } @article {pmid37319115, year = {2023}, author = {Yang, F and Mahaman, YAR and Zhang, B and Wang, JZ and Liu, R and Liu, F and Wang, X}, title = {C9orf72 poly-PR helps p53 escape from the ubiquitin-proteasome system and promotes its stability.}, journal = {Journal of neurochemistry}, volume = {166}, number = {2}, pages = {389-402}, doi = {10.1111/jnc.15872}, pmid = {37319115}, issn = {1471-4159}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism ; Proteasome Endopeptidase Complex/metabolism ; *Frontotemporal Dementia/genetics/metabolism ; Ubiquitin/metabolism ; C9orf72 Protein/genetics/metabolism ; Tumor Suppressor Protein p53/genetics/metabolism ; Cytoplasm/metabolism ; Dipeptides/genetics ; DNA Repeat Expansion ; }, abstract = {C9orf72-derived dipeptide repeats (DPRs) proteins have been regarded as the pathogenic cause of neurodegeneration in amyotrophic lateral sclerosis and frontotemporal dementia (C9-ALS/FTD). As the most toxic DPRs in C9-ALS/FTD, poly-proline-arginine (poly-PR) is associated with the stability and accumulation of p53, which consequently induces neurodegeneration. However, the exact molecular mechanism via which C9orf72 poly-PR stabilizes p53 remains unclear. In this study, we showed that C9orf72 poly-PR induces not only neuronal damage but also p53 accumulation and p53 downstream gene activation in primary neurons. C9orf72 (PR)50 also slows down p53 protein turnover without affecting the p53 transcription level and thus promotes its stability in N2a cells. Interestingly, the ubiquitin-proteasome system but not the autophagy function was impaired in (PR)50 transfected N2a cells, resulting in defective p53 degradation. Moreover, we found that (PR)50 induces mdm2 mistranslocation from the nucleus to the cytoplasm and competitively binds to p53, reducing mdm2-p53 interactions in the nucleus in two different (PR)50 transfected cells. Our data strongly indicate that (PR)50 reduces mdm2-p53 interactions and causes p53 to escape from the ubiquitin-proteasome system, promoting its stability and accumulation. Inhibiting or at least downregulating (PR)50 binding with p53 may be therapeutically exploited for the treatment of C9-ALS/FTD.}, } @article {pmid37318330, year = {2023}, author = {Docherty, SR and Safonova, OV and Copéret, C}, title = {Surface Redox Dynamics in Gold-Zinc CO2 Hydrogenation Catalysts.}, journal = {Journal of the American Chemical Society}, volume = {145}, number = {25}, pages = {13526-13530}, doi = {10.1021/jacs.3c03522}, pmid = {37318330}, issn = {1520-5126}, abstract = {Au-Zn catalysts have previously been shown to promote the hydrogenation of CO2 to methanol, but their active state is poorly understood. Here, silica-supported bimetallic Au-Zn alloys, prepared by surface organometallic chemistry (SOMC), are shown to be proficient catalysts for hydrogenation of CO2 to methanol. In situ X-ray absorption spectroscopy (XAS), in conjunction with gas-switching experiments, is used to amplify subtle changes occurring at the surface of this tailored catalyst during reaction. Consequently, an Au-Zn alloy is identified and is shown to undergo subsequent reversible redox changes under reaction conditions according to multivariate curve resolution alternating least-squares (MCR-ALS) analysis. These results highlight the role of alloying and dealloying in Au-based CO2 hydrogenation catalysts and illustrate the role of these reversible processes in driving reactivity.}, } @article {pmid37317656, year = {2023}, author = {Jülg, J and Edbauer, D and Behrends, C}, title = {C9orf72 protein quality control by UBR5-mediated heterotypic ubiquitin chains.}, journal = {EMBO reports}, volume = {24}, number = {8}, pages = {e55895}, pmid = {37317656}, issn = {1469-3178}, mesh = {Humans ; C9orf72 Protein/genetics/metabolism ; Ubiquitin/metabolism ; Carrier Proteins/metabolism ; Proteins/genetics/metabolism ; *Frontotemporal Dementia/genetics/metabolism ; *Amyotrophic Lateral Sclerosis/genetics/metabolism ; Ubiquitin-Protein Ligases/genetics/metabolism ; Molecular Chaperones/metabolism ; }, abstract = {Hexanucleotide repeat expansions within C9orf72 are a frequent cause of amyotrophic lateral sclerosis and frontotemporal dementia. Haploinsufficiency leading to reduced C9orf72 protein contributes to disease pathogenesis. C9orf72 binds SMCR8 to form a robust complex that regulates small GTPases, lysosomal integrity, and autophagy. In contrast to this functional understanding, we know far less about the assembly and turnover of the C9orf72-SMCR8 complex. Loss of either subunit causes the concurrent ablation of the respective partner. However, the molecular mechanism underlying this interdependence remains elusive. Here, we identify C9orf72 as a substrate of branched ubiquitin chain-dependent protein quality control. We find that SMCR8 prevents C9orf72 from rapid degradation by the proteasome. Mass spectrometry and biochemical analyses reveal the E3 ligase UBR5 and the BAG6 chaperone complex as C9orf72-interacting proteins, which are components of the machinery that modifies proteins with K11/K48-linked heterotypic ubiquitin chains. Depletion of UBR5 results in reduced K11/K48 ubiquitination and increased C9orf72 when SMCR8 is absent. Our data provide novel insights into C9orf72 regulation with potential implication for strategies to antagonize C9orf72 loss during disease progression.}, } @article {pmid37317638, year = {2023}, author = {Yang, Y and Rowe, D and McCann, H and Shepherd, CE and Kril, JJ and Kiernan, MC and Halliday, GM and Tan, RH}, title = {Treatment with the copper compound CuATSM has no significant effect on motor neuronal pathology in patients with ALS.}, journal = {Neuropathology and applied neurobiology}, volume = {49}, number = {4}, pages = {e12919}, pmid = {37317638}, issn = {1365-2990}, support = {R28 AA012725/AA/NIAAA NIH HHS/United States ; }, mesh = {Mice ; Animals ; *Amyotrophic Lateral Sclerosis/drug therapy/pathology ; Copper ; Superoxide Dismutase-1 ; Riluzole ; Superoxide Dismutase ; Motor Neurons/pathology ; Spinal Cord/pathology ; DNA-Binding Proteins ; Mice, Transgenic ; }, abstract = {AIMS: Although the orally available brain-penetrant copper compound CuATSM has demonstrated promising effects in SOD1-linked mouse models, the impact of CuATSM on disease pathology in patients with amyotrophic lateral sclerosis (ALS) remains unknown.

METHODS: The present study set out to address this deficit by performing the first pilot comparative analysis of ALS pathology in patients that had been administered CuATSM and riluzole [N = 6 cases composed of ALS-TDP (n = 5) and ALS-SOD1 (n = 1)] versus riluzole only [N = 6 cases composed of ALS-TDP (n = 4) and ALS-SOD1 (n = 2)].

RESULTS: Our results revealed no significant difference in neuron density or TDP-43 burden in the motor cortex and spinal cord of patients that had received CuATSM compared with patients that had not. In patients that had received CuATSM, p62-immunoreactive astrocytes were observed in the motor cortex and reduced Iba1 density was found in the spinal cord. However, no significant difference in measures of astrocytic activity and SOD1 immunoreactivity was found with CuATSM treatment.

DISCUSSION: These findings, in this first postmortem investigation of patients with ALS in CuATSM trials, demonstrate that in contrast to that seen in preclinical models of disease, CuATSM does not significantly alleviate neuronal pathology or astrogliosis in patients with ALS.}, } @article {pmid37316950, year = {2023}, author = {Petri, S and Grehl, T and Grosskreutz, J and Hecht, M and Hermann, A and Jesse, S and Lingor, P and Löscher, W and Maier, A and Schoser, B and Weber, M and Ludolph, AC}, title = {Guideline "Motor neuron diseases" of the German Society of Neurology (Deutsche Gesellschaft für Neurologie).}, journal = {Neurological research and practice}, volume = {5}, number = {1}, pages = {25}, pmid = {37316950}, issn = {2524-3489}, abstract = {INTRODUCTION: In 2021, the Deutsche Gesellschaft für Neurology published a new guideline on diagnosis and therapy of motor neuron disorders. Motor neuron disorders affect upper motor neurons in the primary motor cortex and/or lower motor neurons in the brain stem and spinal cord. The most frequent motor neuron disease amyotrophic lateral sclerosis (ALS) is a rapidly progressive disease with an average life expectancy of 2-4 years with a yearly incidence of 3.1/100,000 in Central Europe (Rosenbohm et al. in J Neurol 264(4):749-757, 2017. https://doi.org/10.1007/s00415-017-8413-3). It is considered a rare disease mainly due to its low prevalence as a consequence of short disease duration.

RECOMMENDATIONS: These guidelines comprise recommendations regarding differential diagnosis, neuroprotective therapies and multidisciplinary palliative care including management of respiration and nutrition as well as provision of assistive devices and end-of-life situations.

CONCLUSION: Diagnostic and therapeutic guidelines are necessary due the comparatively high number of cases and the aggressive disease course. Given the low prevalence and the severe impairment of patients, it is often impossible to generate evidence-based data so that ALS guidelines are partially dependent on expert opinion.}, } @article {pmid37316681, year = {2023}, author = {Blair, HA}, title = {Tofersen: First Approval.}, journal = {Drugs}, volume = {83}, number = {11}, pages = {1039-1043}, pmid = {37316681}, issn = {1179-1950}, mesh = {Adult ; Humans ; *Amyotrophic Lateral Sclerosis/drug therapy/genetics ; Superoxide Dismutase/genetics ; Oligonucleotides/pharmacology/therapeutic use ; Superoxide Dismutase-1/genetics ; Mutation ; }, abstract = {Tofersen (Qalsody[™]) is an antisense oligonucleotide being developed by Biogen for the treatment of amyotrophic lateral sclerosis (ALS). On 25 April 2023, tofersen was approved in the USA for the treatment of ALS in adults who have a mutation in the superoxide dismutase 1 (SOD1) gene. This article summarizes the milestones in the development of tofersen leading to this first approval for ALS.}, } @article {pmid37316187, year = {2023}, author = {Iverson, GL and Castellani, RJ and Cassidy, JD and Schneider, GM and Schneider, KJ and Echemendia, RJ and Bailes, JE and Hayden, KA and Koerte, IK and Manley, GT and McNamee, M and Patricios, JS and Tator, CH and Cantu, RC and Dvorak, J}, title = {Examining later-in-life health risks associated with sport-related concussion and repetitive head impacts: a systematic review of case-control and cohort studies.}, journal = {British journal of sports medicine}, volume = {57}, number = {12}, pages = {810-821}, doi = {10.1136/bjsports-2023-106890}, pmid = {37316187}, issn = {1473-0480}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis ; *Sports ; *Brain Concussion/epidemiology/etiology ; Cohort Studies ; Case-Control Studies ; *Dementia ; }, abstract = {OBJECTIVE: Concern exists about possible problems with later-in-life brain health, such as cognitive impairment, mental health problems and neurological diseases, in former athletes. We examined the future risk for adverse health effects associated with sport-related concussion, or exposure to repetitive head impacts, in former athletes.

DESIGN: Systematic review.

DATA SOURCES: Search of MEDLINE, Embase, Cochrane, CINAHL Plus and SPORTDiscus in October 2019 and updated in March 2022.

ELIGIBILITY CRITERIA: Studies measuring future risk (cohort studies) or approximating that risk (case-control studies).

RESULTS: Ten studies of former amateur athletes and 18 studies of former professional athletes were included. No postmortem neuropathology studies or neuroimaging studies met criteria for inclusion. Depression was examined in five studies in former amateur athletes, none identifying an increased risk. Nine studies examined suicidality or suicide as a manner of death, and none found an association with increased risk. Some studies comparing professional athletes with the general population reported associations between sports participation and dementia or amyotrophic lateral sclerosis (ALS) as a cause of death. Most did not control for potential confounding factors (eg, genetic, demographic, health-related or environmental), were ecological in design and had high risk of bias.

CONCLUSION: Evidence does not support an increased risk of mental health or neurological diseases in former amateur athletes with exposure to repetitive head impacts. Some studies in former professional athletes suggest an increased risk of neurological disorders such as ALS and dementia; these findings need to be confirmed in higher quality studies with better control of confounding factors.

PROSPERO REGISTRATION NUMBER: CRD42022159486.}, } @article {pmid37316165, year = {2023}, author = {Ziegler, A and Öner, A and Quadflieg, G and Betschart, RO and Thiéry, A and Babel, H and Mwambi, HG and Neumeyer, H and Mackschin, S and Hintz, S and Mann, M and Dittrich, H and Schmidt, C}, title = {Cost-effectiveness of a telemonitoring programme in patients with cardiovascular diseases compared with standard of care.}, journal = {Heart (British Cardiac Society)}, volume = {109}, number = {21}, pages = {1617-1623}, pmid = {37316165}, issn = {1468-201X}, mesh = {Humans ; *Cardiovascular Diseases/therapy ; Cost-Benefit Analysis ; Quality of Life ; Standard of Care ; *Hypertension/diagnosis/therapy ; Quality-Adjusted Life Years ; }, abstract = {OBJECTIVES: The main aim of this work was to analyse the cost-effectiveness of an integrated care concept (NICC) that combines telemonitoring with the support of a care centre in addition to guideline therapy for patients. Secondary aims were to compare health utility and health-related quality of life (QoL) between NICC and standard of care (SoC).

METHODS: The randomised controlled CardioCare MV Trial compared NICC and SoC in patients from Mecklenburg-West Pomerania (Germany) with atrial fibrillation, heart failure or treatment-resistant hypertension. QoL was measured using the EQ-5D-5L at baseline, 6 months and 1 year follow-up. Quality-adjusted life years (QALYs), EQ5D utility scores, Visual Analogue Scale (VAS) Scores and VAS adjusted life years (VAS-AL) were calculated. Cost data were obtained from health insurance companies, and the payer perspective was taken in health economic analyses. Quantile regression was used with adjustments for stratification variables.

RESULTS: The net benefit of NICC (QALY) was 0.031 (95% CI 0.012 to 0.050; p=0.001) in this trial involving 957 patients. EQ5D Index values, VAS-ALs and VAS were larger for NICC compared with SoC at 1 year follow-up (all p≤0.004). Direct cost per patient and year were €323 (CI €157 to €489) lower in the NICC group. When 2000 patients are served by the care centre, NICC is cost-effective if one is willing to pay €10 652 per QALY per year.

CONCLUSION: NICC was associated with higher QoL and health utility. The programme is cost-effective if one is willing to pay approximately €11 000 per QALY per year.}, } @article {pmid37316101, year = {2023}, author = {Tavazzi, E and Longato, E and Vettoretti, M and Aidos, H and Trescato, I and Roversi, C and Martins, AS and Castanho, EN and Branco, R and Soares, DF and Guazzo, A and Birolo, G and Pala, D and Bosoni, P and Chiò, A and Manera, U and de Carvalho, M and Miranda, B and Gromicho, M and Alves, I and Bellazzi, R and Dagliati, A and Fariselli, P and Madeira, SC and Di Camillo, B}, title = {Artificial intelligence and statistical methods for stratification and prediction of progression in amyotrophic lateral sclerosis: A systematic review.}, journal = {Artificial intelligence in medicine}, volume = {142}, number = {}, pages = {102588}, doi = {10.1016/j.artmed.2023.102588}, pmid = {37316101}, issn = {1873-2860}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis ; Artificial Intelligence ; Brain ; Cluster Analysis ; Databases, Factual ; }, abstract = {BACKGROUND: Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disorder characterised by the progressive loss of motor neurons in the brain and spinal cord. The fact that ALS's disease course is highly heterogeneous, and its determinants not fully known, combined with ALS's relatively low prevalence, renders the successful application of artificial intelligence (AI) techniques particularly arduous.

OBJECTIVE: This systematic review aims at identifying areas of agreement and unanswered questions regarding two notable applications of AI in ALS, namely the automatic, data-driven stratification of patients according to their phenotype, and the prediction of ALS progression. Differently from previous works, this review is focused on the methodological landscape of AI in ALS.

METHODS: We conducted a systematic search of the Scopus and PubMed databases, looking for studies on data-driven stratification methods based on unsupervised techniques resulting in (A) automatic group discovery or (B) a transformation of the feature space allowing patient subgroups to be identified; and for studies on internally or externally validated methods for the prediction of ALS progression. We described the selected studies according to the following characteristics, when applicable: variables used, methodology, splitting criteria and number of groups, prediction outcomes, validation schemes, and metrics.

RESULTS: Of the starting 1604 unique reports (2837 combined hits between Scopus and PubMed), 239 were selected for thorough screening, leading to the inclusion of 15 studies on patient stratification, 28 on prediction of ALS progression, and 6 on both stratification and prediction. In terms of variables used, most stratification and prediction studies included demographics and features derived from the ALSFRS or ALSFRS-R scores, which were also the main prediction targets. The most represented stratification methods were K-means, and hierarchical and expectation-maximisation clustering; while random forests, logistic regression, the Cox proportional hazard model, and various flavours of deep learning were the most widely used prediction methods. Predictive model validation was, albeit unexpectedly, quite rarely performed in absolute terms (leading to the exclusion of 78 eligible studies), with the overwhelming majority of included studies resorting to internal validation only.

CONCLUSION: This systematic review highlighted a general agreement in terms of input variable selection for both stratification and prediction of ALS progression, and in terms of prediction targets. A striking lack of validated models emerged, as well as a general difficulty in reproducing many published studies, mainly due to the absence of the corresponding parameter lists. While deep learning seems promising for prediction applications, its superiority with respect to traditional methods has not been established; there is, instead, ample room for its application in the subfield of patient stratification. Finally, an open question remains on the role of new environmental and behavioural variables collected via novel, real-time sensors.}, } @article {pmid37315804, year = {2023}, author = {Helm, M and Helm, T and Helm, K and Foulke, G}, title = {Response to Jerjen et al's "Systemic sclerosis in adults. Part I: clinical features and pathogenesis".}, journal = {Journal of the American Academy of Dermatology}, volume = {89}, number = {4}, pages = {e171}, doi = {10.1016/j.jaad.2023.04.074}, pmid = {37315804}, issn = {1097-6787}, mesh = {Humans ; Adult ; *Scleroderma, Systemic/diagnosis ; *Scleroderma, Localized ; }, } @article {pmid37315803, year = {2023}, author = {Barry, R and Murray, G and Hazel, K and Ryan, J and Watchorn, RE}, title = {Response to Pan et al's "Non-melanoma skin cancer in patients with hereditary hemochromatosis: A case-control study".}, journal = {Journal of the American Academy of Dermatology}, volume = {89}, number = {4}, pages = {e167-e168}, doi = {10.1016/j.jaad.2023.05.078}, pmid = {37315803}, issn = {1097-6787}, mesh = {Humans ; Case-Control Studies ; *Hemochromatosis/complications/epidemiology/genetics ; *Skin Neoplasms/epidemiology ; *Carcinoma, Basal Cell ; }, } @article {pmid37315438, year = {2023}, author = {Yang, HC and Park, SM and Lee, KJ and Jo, YH and Kim, YJ and Lee, DK and Jang, DH}, title = {Delayed arrival of advanced life support adversely affects the neurological outcome in a multi-tier emergency response system.}, journal = {The American journal of emergency medicine}, volume = {71}, number = {}, pages = {1-6}, doi = {10.1016/j.ajem.2023.06.001}, pmid = {37315438}, issn = {1532-8171}, mesh = {Adult ; Humans ; Electric Countershock ; *Emergency Medical Services ; *Out-of-Hospital Cardiac Arrest/therapy ; Retrospective Studies ; *Advanced Cardiac Life Support ; }, abstract = {AIM: Prehospital management of out-of-hospital cardiac arrest (OHCA) is based on basic life support, with the addition of advanced life support (ALS) if possible. This study aimed to investigate the effect of delayed arrival of ALS on neurological outcomes of patients with OHCA at hospital discharge.

METHODS: This was a retrospective study of a registry of patients with OHCA. A multi-tier emergency response system was established in the study area. ALS was initiated when the second-arrival team arrived at the scene. A restricted cubic spline curve was used to investigate the relationship between the response time interval of the second-arrival team and neurological outcomes at hospital discharge. Multivariable logistic regression analysis was performed to assess the independent association between the response time interval of the second-arrival team and neurological outcomes of patients at hospital discharge.

RESULTS: A total of 3186 adult OHCA patients who received ALS at the scene were included in the final analysis. A restricted cubic spline curve showed that a long response time interval of the second-arrival team was correlated with a high likelihood of poor neurological outcomes. Meanwhile, multivariable logistic regression analysis showed that a long response time interval of the second-arrival team was independently associated with poor neurological outcomes (odds ratio, 1.10; 95% confidence interval, 1.03-1.17).

CONCLUSION: In a multi-tiered prehospital emergency response system, the delayed arrival of ALS was associated with poor neurological outcomes at hospital discharge.}, } @article {pmid37315423, year = {2023}, author = {Tracey, TJ and Jiang, L and Gill, MK and Ranie, SN and Ovchinnikov, DA and Wolvetang, EJ and Ngo, ST}, title = {Generation of a human induced pluripotent stem cell line (UQi001-A-1) edited with the CRISPR-Cas9 system to carry the heterozygous TARDBP c.1144G > A (p.A382T) missense mutation.}, journal = {Stem cell research}, volume = {70}, number = {}, pages = {103137}, doi = {10.1016/j.scr.2023.103137}, pmid = {37315423}, issn = {1876-7753}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics ; CRISPR-Cas Systems/genetics ; DNA-Binding Proteins/genetics ; *Induced Pluripotent Stem Cells/cytology ; Mutation ; Mutation, Missense ; *Neurodegenerative Diseases/genetics ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease in which the TDP-43 protein is believed to play a central role in disease pathophysiology. Using the CRISPR-Cas9 system, we introduced the heterozygous c.1144G > A (p.A382T) missense mutation in exon 6 of the TARDBP gene into an iPSC line derived from a healthy individual. These edited iPSCs displayed normal cellular morphology, expressed major pluripotency markers, were capable of tri-lineage differentiation, and possessed a normal karyotype.}, } @article {pmid37315349, year = {2023}, author = {Ustun, R and Chalmers, G and Tehrani, D and Uzun, B}, title = {Computational molecular explanation of Soybean AHAS resistance from P197S mutation.}, journal = {Plant physiology and biochemistry : PPB}, volume = {201}, number = {}, pages = {107782}, doi = {10.1016/j.plaphy.2023.107782}, pmid = {37315349}, issn = {1873-2690}, mesh = {Glycine max/genetics/metabolism ; Sulfonamides ; *Herbicides/pharmacology/chemistry ; Mutation/genetics ; Amino Acids ; *Acetolactate Synthase/genetics ; Herbicide Resistance/genetics ; }, abstract = {The first enzyme in the pathway involving branched-chain amino is acetohydroxyacid synthase (AHAS, E.C. 2.2.1.6), which is inhibited by five commercial herbicide families. In this work a computational study of a point mutation of Proline-197-Serine of the Soybean AHAS enzyme, which was obtained by mutagenesis, explains the latter's S197 resistance to the commonly used Chlorsulfuron. Using protein-ligand docking and large-scale sampling and distributions from AlphaFold-generated the resistant and susceptible soybean AHAS protein structure. The computational approach here is scaled to screen for mutation probabilities of protein binding sites, similar to screening compounds for potential hits in therapeutic design using the docking software. P197 and S197 AHAS structures were found to be different even if only one amino acid was changed. The non-specific distribution of bindings in the S197 cavity after the P197S change has been rigorously calculated by RMSD analysis that it would require x20 more concentrations to fill the P197 site by the same amount. There is no previously performed detailed chlorsulfuron soybean P197S AHAS binding calculation. In the herbicide site of AHAS, several amino acids interact - a computational study could elucidate the optimal choice of point mutations for herbicidal resistance either individually or collectively by mutations one at a time and analyzing the effects with a set of herbicides individually. With a computational approach, enzymes involved in crop research and development could be analyzed more quickly, enabling faster discovery and development of herbicides.}, } @article {pmid37315259, year = {2023}, author = {Kutlubaev, MA and Areprintseva, DK and Pervushina, EV}, title = {[The influence of uric acid on the course of amyotrophic lateral sclerosis].}, journal = {Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova}, volume = {123}, number = {5}, pages = {177-180}, doi = {10.17116/jnevro2023123051177}, pmid = {37315259}, issn = {1997-7298}, mesh = {Male ; Humans ; Uric Acid ; *Amyotrophic Lateral Sclerosis ; *Gout/complications/drug therapy ; Antioxidants/therapeutic use ; Neuroprotection ; }, abstract = {Uric acid has antioxidant and neuroprotective properties. A number of studies show that high levels of uric acid may have a positive influence on the course of amyotrophic lateral sclerosis (ALS), especially in males. The frequency of ALS is lower in patients with gout than in the general population. We present a case of a patient with gout and slowly progressive ALS. More research is needed on the potential role of uric acid in ALS and other neurodegenerative disorders.}, } @article {pmid37314311, year = {2023}, author = {Sharma, S and Tomar, VR and Deep, S}, title = {Myricetin: A Potent Anti-Amyloidogenic Polyphenol against Superoxide Dismutase 1 Aggregation.}, journal = {ACS chemical neuroscience}, volume = {14}, number = {13}, pages = {2461-2475}, doi = {10.1021/acschemneuro.3c00276}, pmid = {37314311}, issn = {1948-7193}, mesh = {Humans ; Superoxide Dismutase-1/metabolism ; *Amyotrophic Lateral Sclerosis/metabolism ; Polyphenols/pharmacology ; Flavonoids/pharmacology ; Superoxide Dismutase/metabolism ; Mutation ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is believed to be caused by the aggregation of misfolded or mutated superoxide dismutase 1 (SOD1). As there is currently no treatment, research into aggregation inhibitors continues. Based on docking, molecular dynamics (MD) simulations, and experimental observations, we propose that myricetin, a plant flavonoid, can act as a potent anti-amyloidogenic polyphenol against SOD1 aggregation. Our MD simulation results showed that myricetin stabilizes the protein interface, destabilizes the preformed fibril, and decreases the rate of fibril elongation. Myricetin inhibits the aggregation of SOD1 in a dose-dependent manner as shown by the ThT aggregation kinetics curves. Our transmission electron microscopy, dynamic light scattering, and circular dichroism experiments indicate that fewer shorter fibrils have formed. Fluorescence spectroscopy results predict the involvement of a static quenching mechanism characterized by a strong binding between protein and myricetin. Importantly, size exclusion chromatography revealed the potential of myricetin for fibril destabilization and depolymerization. These experimental observations complement the MD results. Thus, myricetin is a potent SOD1 aggregation inhibitor that can reduce the fibril load. Using the structure of myricetin as a reference, it is possible to design more effective therapeutic inhibitors against ALS that prevent the disease and reverse its effects.}, } @article {pmid37313936, year = {2023}, author = {Negi, R and Srivastava, A and Srivastava, AK and Pandeya, A and Vatsa, P and Ansari, UA and Pant, AB}, title = {Proteome architecture of human-induced pluripotent stem cell-derived three-dimensional organoids as a tool for early diagnosis of neuronal disorders.}, journal = {Indian journal of pharmacology}, volume = {55}, number = {2}, pages = {108-118}, pmid = {37313936}, issn = {1998-3751}, mesh = {Humans ; Proteome ; *Amyotrophic Lateral Sclerosis/diagnosis/genetics ; *Induced Pluripotent Stem Cells ; Proteomics ; Early Diagnosis ; DNA-Binding Proteins ; Organoids ; }, abstract = {BACKGROUND AND OBJECTIVES: Induced pluripotent stem cells (iPSCs) derived three-dimensional (3D) model for rare neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS) is emerging as a novel alternative to human diseased tissue to explore the disease etiology and potential drug discovery. In the interest of the same, we have generated a TDP-43-mutated human iPSCs (hiPSCs) derived 3D organoid model of ALS disease. The high-resolution mass spectrometry (MS)-based proteomic approach is used to explore the differential mechanism under disease conditions and the suitability of a 3D model to study the disease.

MATERIALS AND METHODS: The hiPSCs cell line was procured from a commercial source, grown, and characterized following standard protocols. The mutation in hiPSCs was accomplished using CRISPR/Cas-9 technology and predesigned gRNA. The two groups of organoids were produced by normal and mutated hiPSCs and subjected to the whole proteomic profiling by high-resolution MS in two biological replicates with three technical replicas of each.

RESULTS: The proteomic analysis of normal and mutated organoids revealed the proteins associated with pathways of neurodegenerative disorders, proteasomes, autophagy, and hypoxia-inducible factor-1 signaling. Differential proteomic analysis revealed that the mutation in TDP-43 gene caused proteomic deregulation, which impaired protein quality mechanisms. Furthermore, this impairment may contribute to the generation of stress conditions that may ultimately lead to the development of ALS pathology.

CONCLUSION: The developed 3D model represents the majority of candidate proteins and associated biological mechanisms altered in ALS disease. The study also offers novel protein targets that may uncloud the precise disease pathological mechanism and be considered for future diagnostic and therapeutic purposes for various neurodegenerative disorders.}, } @article {pmid37312655, year = {2023}, author = {Stevens-Jones, O and Malmeström, C and Constantinescu, C and Dalla, K and Nellgård, B and Zelano, J and Constantinescu, R and Axelsson, M}, title = {Presence of neural surface and onconeural autoantibodies in cerebrospinal fluid and serum in neurological diseases presents a potential risk for misdiagnosis.}, journal = {European journal of neurology}, volume = {30}, number = {9}, pages = {2602-2610}, doi = {10.1111/ene.15926}, pmid = {37312655}, issn = {1468-1331}, mesh = {*Multiple Sclerosis/diagnosis ; Diagnostic Errors ; *Parkinson Disease/diagnosis ; Hashimoto Disease ; Encephalitis ; Humans ; Autoantibodies ; }, abstract = {BACKGROUND AND PURPOSE: Autoantibodies have been found to contribute to pathology and are used in the diagnosis of some neurological diseases. We examined the prevalence of autoantibodies in patients with various neurological diseases and whether patients who had autoantibodies differed in age, sex, or disability from those who did not.

METHODS: We examined the prevalence of neural surface and onconeural autoantibodies in cerebrospinal fluid (CSF) and serum from patients with multiple sclerosis (n = 64), Parkinson disease plus atypical parkinsonism (n = 150), amyotrophic lateral sclerosis (n = 43), or autoimmune encephalitis (positive control; n = 7) and a healthy control group (n = 37). A total of 12 onconeural autoantibodies and six neural surface autoantibodies were tested in all participants.

RESULTS: Autoantibodies were present in all cohorts. The prevalence of autoantibodies was high (>80%) in the autoimmune encephalitis cohort but low (<20%) in all other cohorts. When comparing patients within cohorts who were positive for autoantibodies to patients who were not, there was no difference in age, sex, and disability. This was apart from the multiple sclerosis and Parkinson disease plus atypical parkinsonism cohorts, where those with positivity for autoantibodies in the CSF were significantly older.

CONCLUSIONS: The presence of the autoantibodies examined does not appear to have a substantial clinical impact within the diseases examined in this study. The presence of autoantibodies in all cohorts presents a risk for misdiagnosis when the method is used incorrectly on patients with atypical clinical presentation.}, } @article {pmid37312136, year = {2023}, author = {Ciećwierska, K and Lulé, D and Bielecki, M and Helczyk, O and Maksymowicz-Śliwińska, A and Finsel, J and Nieporęcki, K and Andersen, PM and Ludolph, AC and Kuźma-Kozakiewicz, M}, title = {Quality of life and depression in patients with amyotrophic lateral sclerosis - does the country of origin matter?.}, journal = {BMC palliative care}, volume = {22}, number = {1}, pages = {72}, pmid = {37312136}, issn = {1472-684X}, support = {JPND; 01ED1405//EU Joint Program - Neurodegenerative Disease Research project/ ; JPND; 01ED1405//EU Joint Program - Neurodegenerative Disease Research project/ ; JPND; 01ED1405//EU Joint Program - Neurodegenerative Disease Research project/ ; LU 336/13-2 BI 195/54-2//Deutsche Forschungsgemeinschaft/ ; LU 336/13-2 BI 195/54-2//Deutsche Forschungsgemeinschaft/ ; LU 336/13-2 BI 195/54-2//Deutsche Forschungsgemeinschaft/ ; 3/IV/MAXOMOD/11.2020//ERA-NET-E Rare/ ; 3/IV/MAXOMOD/11.2020//ERA-NET-E Rare/ ; KAW #2014.0305//the Knut and Alice Wallenberg Foundation/ ; }, mesh = {Humans ; Male ; *Quality of Life ; *Amyotrophic Lateral Sclerosis/complications ; Depression/etiology ; Health Status ; Germany ; }, abstract = {BACKGROUND: Given the inevitable relentless progressing nature of amyotrophic lateral sclerosis (ALS), it is essential to identify factors influencing patients' wellbeing. The study aimed to prospectively assess factors influencing the quality of life (QoL) and depression in ALS patients compared to healthy controls (HCs) from Poland, Germany and Sweden and their relationship to socio-demographic and clinical factors.

METHODS: 314 ALS patients (120 from Poland, 140 from Germany, 54 from Sweden) and 311 age-, sex- and education-level-matched HCs underwent standardized interviews for quality of life, depression, functional status and pain.

RESULTS: Patients from all three countries showed similar levels of functional impairment (ALSFRS-R). Overall, ALS patients assessed their quality of life as lower compared to HCs (p < 0.001 for the anamnestic comparative self-assessment (ACSA), p = 0.002 for the Schedule for the evaluation of the subjective quality of life - SEIQoL- direct weighting (SEIQoL-DW). Also, the German and Swedish patients, but not the Polish, reported higher depression levels than the corresponding HCs (p < 0.001). Analysis of ALS groups revealed that functional impairment was related to a lower quality of life (ACSA) and higher depression levels among German ALS patients. Longer time since diagnosis predicted lower depression and (in male subjects) higher quality of life.

CONCLUSIONS: ALS patients assess their quality of life and mood lower than healthy individuals within the studied countries. The relationships between clinical and demographic factors are moderated by country of provenance, which bears implications for the design and interpretation of scientific and clinical studies, which should reflect the complexity and heterogeneity of mechanisms determining QoL.}, } @article {pmid37311649, year = {2023}, author = {de Jongh, AD and van Eijk, RPA and Bakker, LA and Bunte, TM and Beelen, A and van der Meijden, C and van Es, MA and Visser-Meily, JMA and Kruitwagen, ET and Veldink, JH and van den Berg, LH}, title = {Development of a Rasch-Built Amyotrophic Lateral Sclerosis Impairment Multidomain Scale to Measure Disease Progression in ALS.}, journal = {Neurology}, volume = {101}, number = {6}, pages = {e602-e612}, pmid = {37311649}, issn = {1526-632X}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis ; Reproducibility of Results ; Prognosis ; Probability ; Disease Progression ; }, abstract = {BACKGROUND AND OBJECTIVES: Current scales used in amyotrophic lateral sclerosis (ALS) attempt to summarize different functional domains or "dimensions" into 1 overall score, which may not accurately characterize the individual patient's disease severity or prognosis. The use of composite score risks declaring treatments ineffective if not all dimensions of ALS disease progression are affected equally. We aimed to develop the ALS Impairment Multidomain Scale (AIMS) to comprehensively characterize disease progression and increase the likelihood of identifying effective treatments.

METHODS: The Revised ALS Functional Rating Scale (ALSFRS-R) and a preliminary questionnaire, based on literature review and patient input, were completed online by patients from the Netherlands ALS registry at bimonthly intervals over a period of 12 months. A 2-week test-retest, factor analysis, Rasch analysis, and a signal-to-noise optimization strategy were performed to create a multidomain scale. Reliability, longitudinal decline, and associations with survival were evaluated. The sample size required to detect a 35% reduction in progression rate over 6 or 12 months was assessed for a clinical trial that defines the ALSFRS-R or AIMS subscales as a primary endpoint family.

RESULTS: The preliminary questionnaire, consisting of 110 questions, was completed by 367 patients. Three unidimensional subscales were identified, and a multidomain scale was constructed with 7 bulbar, 11 motor, and 5 respiratory questions. Subscales fulfilled Rasch model requirements, with excellent test-retest reliability of 0.91-0.94 and a strong relationship with survival (p < 0.001). Compared with the ALSFRS-R, signal-to-noise ratios were higher as patients declined more uniformly per subscale. Consequently, the estimated sample size reductions achieved with the AIMS compared with those achieved with the ALSFRS-R were 16.3% and 25.9% for 6-month and 12-month clinical trials, respectively.

DISCUSSION: We developed the AIMS, consisting of unidimensional bulbar, motor, and respiratory subscales, which may characterize disease severity better than a total score. AIMS subscales have high test-retest reliability, are optimized to measure disease progression, and are strongly related to survival time. The AIMS can be easily administered and may increase the likelihood of identifying effective treatments in ALS clinical trials.}, } @article {pmid37310359, year = {2023}, author = {Fang, J and Huang, Y and Wu, J and Shen, B and Yang, Y and Ju, M}, title = {Fluorogenic methodology for visualization of phase separation in chemical biology.}, journal = {Organic & biomolecular chemistry}, volume = {21}, number = {25}, pages = {5140-5149}, doi = {10.1039/d3ob00660c}, pmid = {37310359}, issn = {1477-0539}, mesh = {Humans ; *Alzheimer Disease ; Biology ; }, abstract = {Phase separation is a common biological phenomenon in the liquid environment of organisms. Phase separation has been shown to be a key cause of many existing incurable diseases, such as the protein aggregates formed by phase separation of Alzheimer's Disease, Amyotrophic Lateral Sclerosis, Parkinson's disease, etc. Tracking the occurrence of phase separation in vivo is critical to many disease detection methods and solving many treatment problems. Its physicochemical properties and visual detection methods have flourished in the last few years in chemical biology, among which the fluorogenic toolbox has great application potential compared to the traditional detection methods that cannot visualize the phase separation process intuitively, but just show some parameters indirectly. This paper reviews the mechanism and disease correlation proven in recent years for phase separation and analyzes the detection methods for phase separation, including functional microscope imaging techniques, turbidity monitoring, macromolecule congestion sensing, in silico analysis, etc. It is worth mentioning that the qualitative and quantitative analysis of aggregates formed by phase separation using in vitro parameters has successfully provided basic physical and chemical properties for phase separation aggregates, and is an important cornerstone for researchers to carry forward the past and break through the existing technical shackles to create new in vivo monitoring methods such as fluorescence methodology. Crucially, fluorescence methods for cell microenvironment imaging based on different mechanisms are discussed, such as AIE-based probes, TICT-based probes and FRET-based probes, etc.}, } @article {pmid37310119, year = {2023}, author = {Jackson, IM and Carlson, ML and Beinat, C and Malik, N and Kalita, M and Reyes, S and Azevedo, EC and Nagy, SC and Alam, IS and Sharma, R and La Rosa, SA and Moradi, F and Cleland, J and Shen, B and James, ML}, title = {Clinical Radiosynthesis and Translation of [[18]F]OP-801: A Novel Radiotracer for Imaging Reactive Microglia and Macrophages.}, journal = {ACS chemical neuroscience}, volume = {14}, number = {13}, pages = {2416-2424}, pmid = {37310119}, issn = {1948-7193}, support = {T32 GM007365/GM/NIGMS NIH HHS/United States ; T32 GM145402/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Humans ; Mice ; Brain ; Fluorine Radioisotopes/chemistry ; Macrophages ; *Microglia ; *Positron-Emission Tomography/methods ; Radiopharmaceuticals/chemistry ; Clinical Trials, Phase I as Topic ; Clinical Trials, Phase II as Topic ; }, abstract = {Positron emission tomography (PET) is a powerful tool for studying neuroinflammatory diseases; however, current PET biomarkers of neuroinflammation possess significant limitations. We recently reported a promising dendrimer PET tracer ([[18]F]OP-801), which is selectively taken up by reactive microglia and macrophages. Here, we describe further important characterization of [[18]F]OP-801 in addition to optimization and validation of a two-step clinical radiosynthesis. [[18]F]OP-801 was found to be stable in human plasma for 90 min post incubation, and human dose estimates were calculated for 24 organs of interest; kidneys and urinary bladder wall without bladder voiding were identified as receiving the highest absorbed dose. Following optimization detailed herein, automated radiosynthesis and quality control (QC) analyses of [[18]F]OP-801 were performed in triplicate in suitable radiochemical yield (6.89 ± 2.23% decay corrected), specific activity (37.49 ± 15.49 GBq/mg), and radiochemical purity for clinical imaging. Importantly, imaging mice with tracer (prepared using optimized methods) 24 h following the intraperitoneal injection of liposaccharide resulted in the robust brain PET signal. Cumulatively, these data enable clinical translation of [[18]F]OP-801 for imaging reactive microglia and macrophages in humans. Data from three validation runs of the clinical manufacturing and QC were submitted to the Food and Drug Administration (FDA) as part of a Drug Master File (DMF). Subsequent FDA approval to proceed was obtained, and a phase 1/2 clinical trial (NCT05395624) for first-in-human imaging in healthy controls and patients with amyotrophic lateral sclerosis is underway.}, } @article {pmid37309712, year = {2023}, author = {Ribeiro, VHV and Brunharo, CA and Mallory-Smith, C and Walenta, DL and Barroso, J}, title = {First report of target-site resistance to ACCase-inhibiting herbicides in Bromus tectorum L.}, journal = {Pest management science}, volume = {79}, number = {10}, pages = {4025-4033}, doi = {10.1002/ps.7607}, pmid = {37309712}, issn = {1526-4998}, support = {//Oregon Fine Fescue Comission/ ; }, mesh = {*Bromus ; *Herbicides/pharmacology ; Herbicide Resistance/genetics ; Mutation ; Acetyl-CoA Carboxylase/genetics ; Enzyme Inhibitors/pharmacology ; }, abstract = {BACKGROUND: The prevalent and repeated use of acetyl-coenzyme A carboxylase (ACCase)-inhibiting herbicides for Bromus tectorum L. control in fine fescue (Festuca L. spp) grown for seed has selected ACCase-resistant B. tectorum populations. The objectives of this study were to (1) evaluate the response of nine B. tectorum populations to the ACCase inhibitors clethodim, sethoxydim, fluazifop-P-butyl, and quizalofop-P-ethyl and the acetolactate synthase (ALS) inhibitor sulfosulfuron and (2) characterize the resistance mechanisms.

RESULTS: Bromus tectorum populations were confirmed to be resistant to the ACCase-inhibiting herbicides tested. The levels of resistance varied among the populations for clethodim (resistance ratio, RR = 5.1-14.5), sethoxydim (RR = 18.7-44.7), fluazifop-P-butyl (RR = 3.1-40.3), and quizalofop-P-ethyl (RR = 14.5-36). Molecular investigations revealed that the mutations Ile2041Thr and Gly2096Ala were the molecular basis of resistance to the ACCase-inhibiting herbicides. The Gly2096Ala mutation resulted in cross-resistance to the aryloxyphenoxypropionate (APP) herbicides fluazifop-P-butyl and quizalofop-P-ethyl, and the cyclohexanedione (CHD) herbicides clethodim, and sethoxydim, whereas Ile2041Thr mutation resulted in resistance only to the two APP herbicides. All B. tectorum populations were susceptible to sulfosulfuron (RR = 0.3-1.7).

CONCLUSIONS: This is the first report of target-site mutations conferring resistance to ACCase-inhibiting herbicides in B. tectorum. The results of this study suggest multiple evolutionary origins of resistance and contribute to understanding the patterns of cross-resistance to ACCase inhibitors associated with different mutations in B. tectorum. © 2023 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.}, } @article {pmid37309077, year = {2023}, author = {Stegmann, G and Charles, S and Liss, J and Shefner, J and Rutkove, S and Berisha, V}, title = {A speech-based prognostic model for dysarthria progression in ALS.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {}, number = {}, pages = {1-6}, pmid = {37309077}, issn = {2167-9223}, support = {R01 DC006859/DC/NIDCD NIH HHS/United States ; R43 DC017625/DC/NIDCD NIH HHS/United States ; }, abstract = {Objective: We demonstrated that it was possible to predict ALS patients' degree of future speech impairment based on past data. We used longitudinal data from two ALS studies where participants recorded their speech on a daily or weekly basis and provided ALSFRS-R speech subscores on a weekly or quarterly basis (quarter-annually). Methods: Using their speech recordings, we measured articulatory precision (a measure of the crispness of pronunciation) using an algorithm that analyzed the acoustic signal of each phoneme in the words produced. First, we established the analytical and clinical validity of the measure of articulatory precision, showing that the measure correlated with perceptual ratings of articulatory precision (r = .9). Second, using articulatory precision from speech samples from each participant collected over a 45-90 day model calibration period, we showed it was possible to predict articulatory precision 30-90 days after the last day of the model calibration period. Finally, we showed that the predicted articulatory precision scores mapped onto ALSFRS-R speech subscores. Results: the mean absolute error was as low as 4% for articulatory precision and 14% for ALSFRS-R speech subscores relative to the total range of their respective scales. Conclusion: Our results demonstrated that a subject-specific prognostic model for speech predicts future articulatory precision and ALSFRS-R speech values accurately.}, } @article {pmid37308477, year = {2023}, author = {Xie, T and Liu, P and Wu, X and Dong, F and Zhang, Z and Yue, J and Mahawar, U and Farooq, F and Vohra, H and Fang, Q and Liu, W and Wattenberg, BW and Gong, X}, title = {Ceramide sensing by human SPT-ORMDL complex for establishing sphingolipid homeostasis.}, journal = {Nature communications}, volume = {14}, number = {1}, pages = {3475}, pmid = {37308477}, issn = {2041-1723}, support = {R21 NS120128/NS/NINDS NIH HHS/United States ; }, mesh = {Humans ; Child ; *Ceramides ; Sphingolipids ; *Amyotrophic Lateral Sclerosis ; Binding Sites ; Homeostasis ; }, abstract = {The ORM/ORMDL family proteins function as regulatory subunits of the serine palmitoyltransferase (SPT) complex, which is the initiating and rate-limiting enzyme in sphingolipid biosynthesis. This complex is tightly regulated by cellular sphingolipid levels, but the sphingolipid sensing mechanism is unknown. Here we show that purified human SPT-ORMDL complexes are inhibited by the central sphingolipid metabolite ceramide. We have solved the cryo-EM structure of the SPT-ORMDL3 complex in a ceramide-bound state. Structure-guided mutational analyses reveal the essential function of this ceramide binding site for the suppression of SPT activity. Structural studies indicate that ceramide can induce and lock the N-terminus of ORMDL3 into an inhibitory conformation. Furthermore, we demonstrate that childhood amyotrophic lateral sclerosis (ALS) variants in the SPTLC1 subunit cause impaired ceramide sensing in the SPT-ORMDL3 mutants. Our work elucidates the molecular basis of ceramide sensing by the SPT-ORMDL complex for establishing sphingolipid homeostasis and indicates an important role of impaired ceramide sensing in disease development.}, } @article {pmid37308302, year = {2023}, author = {Wolfson, C and Gauvin, DE and Ishola, F and Oskoui, M}, title = {Global Prevalence and Incidence of Amyotrophic Lateral Sclerosis: A Systematic Review.}, journal = {Neurology}, volume = {101}, number = {6}, pages = {e613-e623}, pmid = {37308302}, issn = {1526-632X}, mesh = {*Amyotrophic Lateral Sclerosis/epidemiology ; Incidence ; Prevalence ; Humans ; Africa/epidemiology ; Asia/epidemiology ; Europe/epidemiology ; North America/epidemiology ; South America/epidemiology ; Oceania/epidemiology ; }, abstract = {BACKGROUND AND OBJECTIVES: Amyotrophic lateral sclerosis (ALS) is a rare neurodegenerative disorder affecting upper and lower motor neurons. Due to its rarity and rapidly progressive nature, studying the epidemiology of ALS is challenging, and a comprehensive picture of the global burden of this disease is lacking. The objective of this systematic review was to describe the global incidence and prevalence of ALS.

METHODS: We searched MEDLINE, Embase, Global Health, PsycInfo, Cochrane Library, and CINAHL to identify articles published between January 1, 2010, and May 6, 2021. Studies that were population based and reported estimates of prevalence, incidence, and/or mortality of ALS were eligible for inclusion. This study focuses on the incidence and prevalence. Quality assessment was performed using a tool developed to evaluate methodology relevant to prevalence and incidence studies. This review was registered with PROSPERO, CRD42021250559.

RESULTS: This search generated 6,238 articles, of which 140 were selected for data extraction and quality assessment. Of these, 85 articles reported on the incidence and 61 on the prevalence of ALS. Incidence ranged from 0.26 per 100,000 person-years in Ecuador to 23.46 per 100,000 person-years in Japan. Point prevalence ranged from 1.57 per 100,000 in Iran to 11.80 per 100,000 in the United States. Many articles identified cases with ALS from multiple data sources.

DISCUSSION: There is variation in reported incidence and prevalence estimates of ALS across the world. While registries are an important and powerful tool to quantify disease burden, such resources are not available everywhere. This results in gaps in reporting of the global epidemiology of ALS, as highlighted by the degree of variation (and quality) in estimates of incidence and prevalence reported in this review.}, } @article {pmid37308278, year = {2023}, author = {Morón-Oset, J and Fischer, LK and Carcolé, M and Giblin, A and Zhang, P and Isaacs, AM and Grönke, S and Partridge, L}, title = {Toxicity of C9orf72-associated dipeptide repeat peptides is modified by commonly used protein tags.}, journal = {Life science alliance}, volume = {6}, number = {9}, pages = {}, pmid = {37308278}, issn = {2575-1077}, support = {WT098565/Z/12/Z/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Animals ; Dipeptides ; C9orf72 Protein ; Peptides ; Genes, Regulator ; *Amyotrophic Lateral Sclerosis ; Drosophila ; *Skin Neoplasms ; }, abstract = {Hexanucleotide repeat expansions in the C9orf72 gene are the most prevalent genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia. Transcripts of the expansions are translated into toxic dipeptide repeat (DPR) proteins. Most preclinical studies in cell and animal models have used protein-tagged polyDPR constructs to investigate DPR toxicity but the effects of tags on DPR toxicity have not been systematically explored. Here, we used Drosophila to assess the influence of protein tags on DPR toxicity. Tagging of 36 but not 100 arginine-rich DPRs with mCherry increased toxicity, whereas adding mCherry or GFP to GA100 completely abolished toxicity. FLAG tagging also reduced GA100 toxicity but less than the longer fluorescent tags. Expression of untagged but not GFP- or mCherry-tagged GA100 caused DNA damage and increased p62 levels. Fluorescent tags also affected GA100 stability and degradation. In summary, protein tags affect DPR toxicity in a tag- and DPR-dependent manner, and GA toxicity might be underestimated in studies using tagged GA proteins. Thus, including untagged DPRs as controls is important when assessing DPR toxicity in preclinical models.}, } @article {pmid37308108, year = {2023}, author = {Kögel, A and Lauerer, M and Zank, D}, title = {[Income of physicians in private practice in Germany: Results of a micro census].}, journal = {Gesundheitswesen (Bundesverband der Arzte des Offentlichen Gesundheitsdienstes (Germany))}, volume = {85}, number = {12}, pages = {1205-1212}, doi = {10.1055/a-2075-7696}, pmid = {37308108}, issn = {1439-4421}, mesh = {Male ; Humans ; Female ; *Censuses ; Germany ; *General Practitioners ; Private Practice ; }, abstract = {EINLEITUNG: Daten zum Einkommen von Ärzt:innen in Deutschland sind bisher nur teilweise verfügbar. Die Einkommen der niedergelassenen Ärzteschaft werden vor allem aus den Praxiserträgen abgeleitet, was aber große Interpretationsspielräume eröffnet. Ziel des Artikels ist es, diese Lücke zu schließen.

METHODIK: Hierfür werden die Einkommensangaben aus dem Mikrozensus 2017 ausgewertet - mit besonderem Fokus auf niedergelassene Ärzt:innen. Neben dem persönlichen Einkommen erfolgt eine Darstellung der Einkommenssituation auf Haushaltsebene. Die Einkommensziffern werden nach Tätigkeitsumfang, Tätigkeitsgruppe (Allgemein-/Fach-/Zahnärzte), Geschlecht und Stadt/Land differenziert.

Das verfügbare persönliche Nettoeinkommen niedergelassener Ärzt:innen beträgt bei Vollzeittätigkeit im Mittel knapp 7.900 € pro Monat. Fachärzt:innen liegen bei 8.250 €, Allgemein- und Zahnärzt:innen bei ca. 7.700 €. Eine finanzielle Benachteiligung von Landärzt:innen lässt sich nicht feststellen, Allgemeinärzt:innen aus Gemeinden<5.000 Einwohnerinnen und Einwohner haben mit 8.700 € sogar das höchste Durchschnittseinkommen - bei einer mittleren Arbeitszeit von 51 Stunden pro Woche. Ärztinnen arbeiten häufiger in Teilzeit als Ärzte. Ein niedrigeres Einkommen resultiert überwiegend aus einem geringeren Tätigkeitsumfang.

INTRODUCTION: Data on the income of physicians in Germany are only partially available to date. The income of physicians in private practice is derived primarily from practice income, but this opens up considerable scope for interpretation. The aim of this article is to close this gap.

METHODOLOGY: For this purpose, the income data from the 2017 micro census were evaluated, with a special focus on physicians in private practice. In addition to personal income, the income situation was presented at the household level. The income figures were differentiated according to the scope of activity, activity group (general practitioners/specialists/dentists), gender and city/country.

RESULTS AND CONCLUSION: The disposable personal income of physicians in private practice was just under € 7,900 per month on average for full-time employment. Specialists earned € 8,250, while general practitioners and dentists earned about € 7,700. Rural physicians were not found to suffer from financial disadvantages; general practitioners from municipalities with<5,000 inhabitants even had the highest average income of € 8,700, with an average working time of 51 hours per week. Female physicians worked part-time more often than did male physicians. A lower income resulted primarily from a lower scope of activity.}, } @article {pmid37307969, year = {2023}, author = {Mavadat, E and Seyedalipour, B and Hosseinkhani, S and Colagar, AH}, title = {Role of charged residues of the "electrostatic loop" of hSOD1 in promotion of aggregation: Implications for the mechanism of ALS-associated mutations under amyloidogenic conditions.}, journal = {International journal of biological macromolecules}, volume = {244}, number = {}, pages = {125289}, doi = {10.1016/j.ijbiomac.2023.125289}, pmid = {37307969}, issn = {1879-0003}, mesh = {Humans ; Superoxide Dismutase-1/genetics/metabolism ; *Amyotrophic Lateral Sclerosis/metabolism ; Superoxide Dismutase/metabolism ; Static Electricity ; Mutation ; Amyloid/chemistry ; }, abstract = {Protein misfolding and amyloid formation are hallmarks of numerous diseases, including amyotrophic lateral sclerosis (ALS), in which hSOD1 aggregation is involved in pathogenesis. We used two point mutations in the electrostatic loop, G138E and T137R, to analyze charge distribution under destabilizing circumstances to gain more about how ALS-linked mutations affect SOD1 protein stability or net repulsive charge. We show that protein charge is important in the ALS disease process using bioinformatics and experiments. The MD simulation findings demonstrate that the mutant protein differs significantly from WT SOD1, which is consistent with the experimental evidence. The specific activity of the wild type was 1.61 and 1.48 times higher than that of the G138E and T137R mutants, respectively. Under amyloid induction conditions, the intensity of intrinsic and ANS fluorescence in both mutants reduced. Increasing the content of β-sheet structures in mutants can be attributed to aggregation propensity, which was confirmed using CD polarimetry and FTIR spectroscopy. Our findings show that two ALS-related mutations promote the formation of amyloid-like aggregates at near physiological pH under destabilizing conditions, which were detected using spectroscopic probes such as Congo red and ThT fluorescence, and also further confirmation of amyloid-like species by TEM. Overall, our results provide evidence supporting the notion that negative charge changes combined with other destabilizing factors play an important role in increasing protein aggregation by reducing repulsive negative charges.}, } @article {pmid37307822, year = {2024}, author = {Chen, S and Cai, X and Lao, L and Wang, Y and Su, H and Sun, H}, title = {Brain-Gut-Microbiota Axis in Amyotrophic Lateral Sclerosis: A Historical Overview and Future Directions.}, journal = {Aging and disease}, volume = {15}, number = {1}, pages = {74-95}, pmid = {37307822}, issn = {2152-5250}, mesh = {Humans ; Aged ; Child, Preschool ; *Amyotrophic Lateral Sclerosis/epidemiology ; *Neurodegenerative Diseases/complications ; *Gastrointestinal Microbiome/physiology ; Brain-Gut Axis ; Brain ; }, abstract = {Amyotrophic Lateral Sclerosis (ALS) is a devastating neurodegenerative disease which is strongly associated with age. The incidence of ALS increases from the age of 40 and peaks between the ages of 65 and 70. Most patients die of respiratory muscle paralysis or lung infections within three to five years of the appearance of symptoms, dealing a huge blow to patients and their families. With aging populations, improved diagnostic methods and changes in reporting criteria, the incidence of ALS is likely to show an upward trend in the coming decades. Despite extensive researches have been done, the cause and pathogenesis of ALS remains unclear. In recent decades, large quantities of studies focusing on gut microbiota have shown that gut microbiota and its metabolites seem to change the evolvement of ALS through the brain-gut-microbiota axis, and in turn, the progression of ALS will exacerbate the imbalance of gut microbiota, thereby forming a vicious cycle. This suggests that further exploration and identification of the function of gut microbiota in ALS may be crucial to break the bottleneck in the diagnosis and treatment of this disease. Hence, the current review summarizes and discusses the latest research advancement and future directions of ALS and brain-gut-microbiota axis, so as to help relevant researchers gain correlative information instantly.}, } @article {pmid37307819, year = {2024}, author = {He, D and Xu, Y and Liu, M and Cui, L}, title = {The Inflammatory Puzzle: Piecing together the Links between Neuroinflammation and Amyotrophic Lateral Sclerosis.}, journal = {Aging and disease}, volume = {15}, number = {1}, pages = {96-114}, pmid = {37307819}, issn = {2152-5250}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics ; Neuroinflammatory Diseases ; *Neurodegenerative Diseases/complications ; Central Nervous System ; Signal Transduction/genetics ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that has a complex genetic basis. Through advancements in genetic screening, researchers have identified more than 40 mutant genes associated with ALS, some of which impact immune function. Neuroinflammation, with abnormal activation of immune cells and excessive production of inflammatory cytokines in the central nervous system, significantly contributes to the pathophysiology of ALS. In this review, we examine recent evidence on the involvement of ALS-associated mutant genes in immune dysregulation, with a specific focus on the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway and N6-methyladenosine (m[6]A)-mediated immune regulation in the context of neurodegeneration. We also discuss the perturbation of immune cell homeostasis in both the central nervous system and peripheral tissues in ALS. Furthermore, we explore the advancements made in the emerging genetic and cell-based therapies for ALS. This review underscores the complex relationship between ALS and neuroinflammation, highlighting the potential to identify modifiable factors for therapeutic intervention. A deeper understanding of the connection between neuroinflammation and the risk of ALS is crucial for advancing effective treatments for this debilitating disorder.}, } @article {pmid37307637, year = {2023}, author = {Tamai, Y and Noda, A and Yamamoto, E}, title = {Estimation of confidence intervals for quantitation of coeluted peaks in liquid chromatography-Photodiode array detection through a combination of multivariate curve resolution-alternating least-square and Bayesian inference techniques.}, journal = {Journal of chromatography. A}, volume = {1704}, number = {}, pages = {464136}, doi = {10.1016/j.chroma.2023.464136}, pmid = {37307637}, issn = {1873-3778}, mesh = {*Confidence Intervals ; Bayes Theorem ; Reproducibility of Results ; Chromatography, Liquid ; Chromatography, High Pressure Liquid/methods ; }, abstract = {There is a dramatic increase in drug candidates that exhibit complex structures and do not comply with Lipinski's rule of five. One of the most critical and complex technical challenges in the quality control of such drug candidates is the control of analogous substances contained in active pharmaceutical ingredients and related formulations. Although the development of ultrahigh-performance liquid chromatography and high-performance columns has improved efficiency per unit time, the difficulty of peak separation to quantify impurities with similar structures and physicochemical properties continues to rise, and so does the probability of failure to achieve the necessary separation. Coeluting peaks observed in the case of high-performance liquid chromatography (HPLC) with photodiode array detection can be separated using the multivariate curve resolution-alternating least-square (MCR-ALS) method exploiting differences in analyte UV spectra. However, relatively large quantitation errors have been observed for coeluting analogous substances, and the reliability of the corresponding quantitative data requires improvement. Herein, Bayesian inference is applied to separation by the MCR-ALS method to develop an algorithm assigning a confidence interval to the quantitative data of each analogous substance. The usefulness and limitations of this approach are tested using two analogs of telmisartan as models. For this test, a simulated two-component HPLC-UV dataset with an intensity ratio (relative to the main peak) of 0.1-1.0 and a resolution of 0.5-1.0 is used. The developed algorithm allows the prediction confidence interval, including the true value, to be assigned to the peak area in almost all cases, even when the intensity ratio, resolution, and signal-to-noise ratio are changed. Finally, the developed algorithm is also evaluated on a real HPLC-UV dataset to confirm that reasonable prediction confidence intervals including true values are assigned to peak areas. In addition to allowing the separation and quantitation of substances such as impurities challenging to separate by HPLC in a scientifically valid manner, which is impossible for conventional HPLC-UV detection, our method can assign confidence intervals to quantitative data. Therefore, the adopted approach is expected to resolve the issues associated with assessing impurities in the quality control of pharmaceuticals.}, } @article {pmid37307220, year = {2023}, author = {Lai, SW}, title = {Comment on Parameswaran et al's "Increased Stroke Risk Following Herpes Zoster Infection and Protection With Zoster Vaccine".}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {77}, number = {5}, pages = {801-802}, doi = {10.1093/cid/ciad352}, pmid = {37307220}, issn = {1537-6591}, mesh = {Humans ; *Herpes Zoster Vaccine ; *Herpes Zoster/complications/epidemiology/prevention & control ; *Stroke/prevention & control ; }, } @article {pmid37306196, year = {2023}, author = {Lloyd, EM and Pinniger, GJ and Murphy, RM and Grounds, MD}, title = {Slow or fast: Implications of myofibre type and associated differences for manifestation of neuromuscular disorders.}, journal = {Acta physiologica (Oxford, England)}, volume = {238}, number = {4}, pages = {e14012}, doi = {10.1111/apha.14012}, pmid = {37306196}, issn = {1748-1716}, mesh = {Male ; Animals ; Female ; *Muscle Fibers, Fast-Twitch ; *Muscle Fibers, Slow-Twitch ; Muscle, Skeletal/physiology ; Muscle Contraction/physiology ; Aging ; Mammals ; }, abstract = {Many neuromuscular disorders can have a differential impact on a specific myofibre type, forming the central premise of this review. The many different skeletal muscles in mammals contain a spectrum of slow- to fast-twitch myofibres with varying levels of protein isoforms that determine their distinctive contractile, metabolic, and other properties. The variations in functional properties across the range of classic 'slow' to 'fast' myofibres are outlined, combined with exemplars of the predominantly slow-twitch soleus and fast-twitch extensor digitorum longus muscles, species comparisons, and techniques used to study these properties. Other intrinsic and extrinsic differences are discussed in the context of slow and fast myofibres. These include inherent susceptibility to damage, myonecrosis, and regeneration, plus extrinsic nerves, extracellular matrix, and vasculature, examined in the context of growth, ageing, metabolic syndrome, and sexual dimorphism. These many differences emphasise the importance of carefully considering the influence of myofibre-type composition on manifestation of various neuromuscular disorders across the lifespan for both sexes. Equally, understanding the different responses of slow and fast myofibres due to intrinsic and extrinsic factors can provide deep insight into the precise molecular mechanisms that initiate and exacerbate various neuromuscular disorders. This focus on the influence of different myofibre types is of fundamental importance to enhance translation for clinical management and therapies for many skeletal muscle disorders.}, } @article {pmid37304072, year = {2023}, author = {Santiago, JA and Potashkin, JA}, title = {Physical activity and lifestyle modifications in the treatment of neurodegenerative diseases.}, journal = {Frontiers in aging neuroscience}, volume = {15}, number = {}, pages = {1185671}, pmid = {37304072}, issn = {1663-4365}, support = {R01 AG062176/AG/NIA NIH HHS/United States ; }, abstract = {Neurodegenerative diseases have reached alarming numbers in the past decade. Unfortunately, clinical trials testing potential therapeutics have proven futile. In the absence of disease-modifying therapies, physical activity has emerged as the single most accessible lifestyle modification with the potential to fight off cognitive decline and neurodegeneration. In this review, we discuss findings from epidemiological, clinical, and molecular studies investigating the potential of lifestyle modifications in promoting brain health. We propose an evidence-based multidomain approach that includes physical activity, diet, cognitive training, and sleep hygiene to treat and prevent neurodegenerative diseases.}, } @article {pmid37303947, year = {2023}, author = {Miura, S and Hiruki, S and Okada, T and Takei, SI and Senzaki, K and Okada, Y and Ochi, M and Tanabe, Y and Ochi, H and Igase, M and Ohyagi, Y and Shibata, H}, title = {Case report: Frontotemporal dementia and amyotrophic lateral sclerosis caused by a missense variant (p.Arg89Trp) in the valosin-containing protein gene.}, journal = {Frontiers in genetics}, volume = {14}, number = {}, pages = {1155998}, pmid = {37303947}, issn = {1664-8021}, abstract = {Frontotemporal dementia and/or amyotrophic lateral sclerosis 6, also known as amyotrophic lateral sclerosis 14, is an autosomal dominant, progressive neurodegenerative disorder caused by various mutations in the valosin-containing protein gene. In this report, we examined a 51-year-old female Japanese patient with frontotemporal dementia and amyotrophic lateral sclerosis. The patient began noticing gait disturbances at the age of 45 years. Neurological examination at the age of 46 years met the Awaji criteria for clinically probable amyotrophic lateral sclerosis. At the age of 49 years, she tended to have poor mood and an aversion to activity. Her symptoms gradually worsened. She required a wheelchair for transport and had difficulty communicating with others because of poor comprehension. She then began to frequently exhibit irritability. Eventually, she was admitted to the psychiatric hospital because uncontrollable violent behavior throughout the day. Longitudinal brain magnetic resonance imaging revealed progressive brain atrophy with temporal dominance, non-progressive cerebellar atrophy, and some non-specific white matter intensities. Brain single photon emission computed tomography showed hypoperfusion in the bilateral temporal lobes and cerebellar hemispheres. Clinical exome sequencing revealed the presence of a heterozygous nonsynonymous variant (NM_007126.5, c.265C>T; p.Arg89Trp) in the valosin-containing protein gene, which was absent in the 1000 Genomes Project, the Exome Aggregation Consortium Database, and the Genome Aggregation Database, and was predicted to be "damaging" by PolyPhen-2 and "deleterious" using SIFT with a Combined Annotation Dependent Depletion score of 35. We also confirmed the absence of this variant in 505 Japanese control subjects. Therefore, we concluded that the variant in the valosin-containing protein gene was responsible for the symptoms of this patient.}, } @article {pmid37303816, year = {2023}, author = {Maurer, L and Brown, M and Saggi, T and Cardiges, A and Kolarcik, CL}, title = {Hindlimb muscle representations in mouse motor cortex defined by viral tracing.}, journal = {Frontiers in neuroanatomy}, volume = {17}, number = {}, pages = {965318}, pmid = {37303816}, issn = {1662-5129}, support = {P40 OD010996/OD/NIH HHS/United States ; }, abstract = {INTRODUCTION: Descending pathways from the cortex to the spinal cord are involved in the control of natural movement. Although mice are widely used to study the neurobiology of movement and as models of neurodegenerative disease, an understanding of motor cortical organization is lacking, particularly for hindlimb muscles.

METHODS: In this study, we used the retrograde transneuronal transport of rabies virus to compare the organization of descending cortical projections to fast- and slow-twitch hindlimb muscles surrounding the ankle joint in mice.

RESULTS: Although the initial stage of virus transport from the soleus muscle (predominantly slow-twitch) appeared to be more rapid than that associated with the tibialis anterior muscle (predominantly fast-twitch), the rate of further transport of virus to cortical projection neurons in layer V was equivalent for the two injected muscles. After appropriate survival times, dense concentrations of layer V projection neurons were identified in three cortical areas: the primary motor cortex (M1), secondary motor cortex (M2), and primary somatosensory cortex (S1).

DISCUSSION: The origin of the cortical projections to each of the two injected muscles overlapped almost entirely within these cortical areas. This organization suggests that cortical projection neurons maintain a high degree of specificity; that is, even when cortical projection neurons are closely located, each neuron could have a distinct functional role (controlling fast- versus slow-twitch and/or extensor versus flexor muscles). Our results represent an important addition to the understanding of the mouse motor system and lay the foundation for future studies investigating the mechanisms underlying motor system dysfunction and degeneration in diseases such as amyotrophic lateral sclerosis and spinal muscular atrophy.}, } @article {pmid37303084, year = {2023}, author = {Liu, Q and Huang, Y and Yang, Q and Peng, H and Wang, J}, title = {An Attention-Aware Long Short-Term Memory-Like Spiking Neural Model for Sentiment Analysis.}, journal = {International journal of neural systems}, volume = {33}, number = {8}, pages = {2350037}, doi = {10.1142/S0129065723500375}, pmid = {37303084}, issn = {1793-6462}, mesh = {Humans ; *Neural Networks, Computer ; Sentiment Analysis ; }, abstract = {LSTM-SNP model is a recently developed long short-term memory (LSTM) network, which is inspired from the mechanisms of spiking neural P (SNP) systems. In this paper, LSTM-SNP is utilized to propose a novel model for aspect-level sentiment analysis, termed as ALS model. The LSTM-SNP model has three gates: reset gate, consumption gate and generation gate. Moreover, attention mechanism is integrated with LSTM-SNP model. The ALS model can better capture the sentiment features in the text to compute the correlation between context and aspect words. To validate the effectiveness of the ALS model for aspect-level sentiment analysis, comparison experiments with 17 baseline models are conducted on three real-life data sets. The experimental results demonstrate that the ALS model has a simpler structure and can achieve better performance compared to these baseline models.}, } @article {pmid37302030, year = {2023}, author = {Rudge, JD}, title = {The Lipid Invasion Model: Growing Evidence for This New Explanation of Alzheimer's Disease.}, journal = {Journal of Alzheimer's disease : JAD}, volume = {94}, number = {2}, pages = {457-470}, pmid = {37302030}, issn = {1875-8908}, mesh = {Humans ; *Alzheimer Disease/pathology ; Amyloid beta-Peptides/metabolism ; Brain/pathology ; Blood-Brain Barrier/metabolism ; Cholesterol ; }, abstract = {The Lipid Invasion Model (LIM) is a new hypothesis for Alzheimer's disease (AD) which argues that AD is a result of external lipid invasion to the brain, following damage to the blood-brain barrier (BBB). The LIM provides a comprehensive explanation of the observed neuropathologies associated with the disease, including the lipid irregularities first described by Alois Alzheimer himself, and accounts for the wide range of risk factors now identified with AD, all of which are also associated with damage to the BBB. This article summarizes the main arguments of the LIM, and new evidence and arguments in support of it. The LIM incorporates and extends the amyloid hypothesis, the current main explanation of the disease, but argues that the greatest cause of late-onset AD is not amyloid-β (Aβ) but bad cholesterol and free fatty acids, let into the brain by a damaged BBB. It suggests that the focus on Aβ is the reason why we have made so little progress in treating the disease in the last 30 years. As well as offering new perspectives for further research into the diagnosis, prevention, and treatment of AD, based on protecting and repairing the BBB, the LIM provides potential new insights into other neurodegenerative diseases such as Parkinson's disease and amyotrophic lateral sclerosis/motor neuron disease.}, } @article {pmid37300059, year = {2023}, author = {Stateczny, A and Halicki, A and Specht, M and Specht, C and Lewicka, O}, title = {Review of Shoreline Extraction Methods from Aerial Laser Scanning.}, journal = {Sensors (Basel, Switzerland)}, volume = {23}, number = {11}, pages = {}, pmid = {37300059}, issn = {1424-8220}, support = {LIDER/10/0030/L-11/19/NCBR/2020//National Centre for Research and Development in Poland/ ; WN/2023/PZ/05//Gdynia Maritime University/ ; }, abstract = {Autonomous technologies are increasingly used in various areas of science. The use of unmanned vehicles for hydrographic surveys in shallow coastal areas requires accurate estimation of shoreline position. This is a nontrivial task, which can be performed using a wide range of sensors and methods. The aim of the publication is to review shoreline extraction methods based solely on data from aerial laser scanning (ALS). This narrative review discusses and critically analyses seven publications drawn up in the last ten years. The discussed papers employed nine different shoreline extraction methods based on aerial light detection and ranging (LiDAR) data. It should be noted that unambiguous evaluation of shoreline extraction methods is difficult or impossible. This is because not all of the methods reported achieved accuracy, the methods were assessed on different datasets, the measurements were conducted using different devices, the water areas differed in geometrical and optical properties, the shorelines had different geometries, and the extent of anthropogenic transformation. The methods proposed by the authors were compared with a wide range of reference methods.}, } @article {pmid37299139, year = {2023}, author = {Zhang, J and Zhang, L and Wang, Q and Liu, J and Sun, Y}, title = {Diurnal Regulation of Leaf Photosynthesis Is Related to Leaf-Age-Dependent Changes in Assimilate Accumulation in Camellia oleifera.}, journal = {Plants (Basel, Switzerland)}, volume = {12}, number = {11}, pages = {}, pmid = {37299139}, issn = {2223-7747}, support = {32001348//the National Natural Science Foundation Project/ ; }, abstract = {In order to clarify the mechanism of diurnal changes in photosynthesis of leaves of different leaf ages in Camellia oleifera, current-year leaves (CLs) and annual leaves (ALs) were used as the test materials to analyze the diurnal changes in photosynthetic parameters, assimilate contents and enzyme activities, as well as structural differences and expression levels of sugar transport regulating genes. The rate of net photosynthesis in CLs and ALs was highest in the morning. During the day, there was a decrease in the CO2 assimilation rate, and this decrease was greater in ALs than in CLs at midday. The maximal efficiency of photosystem II (PSII) photochemistry (Fv/Fm) showed a decreasing trend as the sunlight intensity increased, but no significant difference between CLs and ALs was found. Compared with CLs, ALs showed a greater decrease in the carbon export rate at midday and the levels of sugars and starch increased significantly in ALs, accompanied by higher enzyme activity of sucrose synthetase and ADP-glucose pyrophosphorylase. In addition, compared with CLs, ALs had a larger leaf vein area and higher leaf vein density, as well as higher expression levels of sugar transport regulating genes during the day. It is concluded that the excessive accumulation of assimilate is an important factor contributing to the midday depression of photosynthesis in Camellia oleifera annual leaves on a sunny day. Sugar transporters may play an important regulatory role in excessive accumulation of assimilate in leaves.}, } @article {pmid37299097, year = {2023}, author = {Dominguez-Valenzuela, JA and Palma-Bautista, C and Vazquez-Garcia, JG and Yanniccari, M and Gigón, R and Alcántara-de la Cruz, R and De Prado, R and Portugal, J}, title = {Convergent Adaptation of Multiple Herbicide Resistance to Auxin Mimics and ALS- and EPSPS-Inhibitors in Brassica rapa from North and South America.}, journal = {Plants (Basel, Switzerland)}, volume = {12}, number = {11}, pages = {}, pmid = {37299097}, issn = {2223-7747}, abstract = {Herbicide-resistant weeds have been identified and recorded on every continent where croplands are available. Despite the diversity of weed communities, it is of interest how selection has led to the same consequences in distant regions. Brassica rapa is a widespread naturalized weed that is found throughout temperate North and South America, and it is a frequent weed among winter cereal crops in Argentina and in Mexico. Broadleaf weed control is based on glyphosate that is used prior to sowing and sulfonylureas or mimic auxin herbicides that are used once the weeds have already emerged. This study was aimed at determining whether a convergent phenotypic adaptation to multiple herbicides had occurred in B. rapa populations from Mexico and Argentina by comparing the herbicide sensitivity to inhibitors of the acetolactate synthase (ALS), 5-enolpyruvylshikimate-3-phosphate (EPSPS), and auxin mimics. Five B. rapa populations were analyzed from seeds collected in wheat fields in Argentina (Ar1 and Ar2) and barley fields in Mexico (Mx1, Mx2 and MxS). Mx1, Mx2, and Ar1 populations presented multiple resistance to ALS- and EPSPS-inhibitors and to auxin mimics (2,4-D, MCPA, and fluroxypyr), while the Ar2 population showed resistance only to ALS-inhibitors and glyphosate. Resistance factors ranged from 947 to 4069 for tribenuron-methyl, from 1.5 to 9.4 for 2,4-D, and from 2.7 to 42 for glyphosate. These were consistent with ALS activity, ethylene production, and shikimate accumulation analyses in response to tribenuron-methyl, 2,4-D, and glyphosate, respectively. These results fully support the evolution of the multiple- and cross-herbicide resistance to glyphosate, ALS-inhibitors, and auxinic herbicides in B. rapa populations from Mexico and Argentina.}, } @article {pmid37298586, year = {2023}, author = {Cerasuolo, M and Di Meo, I and Auriemma, MC and Trojsi, F and Maiorino, MI and Cirillo, M and Esposito, F and Polito, R and Colangelo, AM and Paolisso, G and Papa, M and Rizzo, MR}, title = {Iron and Ferroptosis More than a Suspect: Beyond the Most Common Mechanisms of Neurodegeneration for New Therapeutic Approaches to Cognitive Decline and Dementia.}, journal = {International journal of molecular sciences}, volume = {24}, number = {11}, pages = {}, pmid = {37298586}, issn = {1422-0067}, mesh = {Humans ; Iron/metabolism ; *Alzheimer Disease/metabolism ; *Ferroptosis ; *Neurodegenerative Diseases/metabolism ; *Cognitive Dysfunction/drug therapy/etiology/metabolism ; }, abstract = {Neurodegeneration is a multifactorial process that involves multiple mechanisms. Examples of neurodegenerative diseases are Parkinson's disease, multiple sclerosis, Alzheimer's disease, prion diseases such as Creutzfeldt-Jakob's disease, and amyotrophic lateral sclerosis. These are progressive and irreversible pathologies, characterized by neuron vulnerability, loss of structure or function of neurons, and even neuron demise in the brain, leading to clinical, functional, and cognitive dysfunction and movement disorders. However, iron overload can cause neurodegeneration. Dysregulation of iron metabolism associated with cellular damage and oxidative stress is reported as a common event in several neurodegenerative diseases. Uncontrolled oxidation of membrane fatty acids triggers a programmed cell death involving iron, ROS, and ferroptosis, promoting cell death. In Alzheimer's disease, the iron content in the brain is significantly increased in vulnerable regions, resulting in a lack of antioxidant defenses and mitochondrial alterations. Iron interacts with glucose metabolism reciprocally. Overall, iron metabolism and accumulation and ferroptosis play a significant role, particularly in the context of diabetes-induced cognitive decline. Iron chelators improve cognitive performance, meaning that brain iron metabolism control reduces neuronal ferroptosis, promising a novel therapeutic approach to cognitive impairment.}, } @article {pmid37298554, year = {2023}, author = {Michetti, F and Clementi, ME and Di Liddo, R and Valeriani, F and Ria, F and Rende, M and Di Sante, G and Romano Spica, V}, title = {The S100B Protein: A Multifaceted Pathogenic Factor More Than a Biomarker.}, journal = {International journal of molecular sciences}, volume = {24}, number = {11}, pages = {}, pmid = {37298554}, issn = {1422-0067}, mesh = {Humans ; Biomarkers/metabolism ; *Nervous System Diseases ; *Parkinson Disease/metabolism ; *S100 Calcium Binding Protein beta Subunit ; }, abstract = {S100B is a calcium-binding protein mainly concentrated in astrocytes in the nervous system. Its levels in biological fluids are recognized as a reliable biomarker of active neural distress, and more recently, mounting evidence points to S100B as a Damage-Associated Molecular Pattern molecule, which, at high concentration, triggers tissue reactions to damage. S100B levels and/or distribution in the nervous tissue of patients and/or experimental models of different neural disorders, for which the protein is used as a biomarker, are directly related to the progress of the disease. In addition, in experimental models of diseases such as Alzheimer's and Parkinson's diseases, amyotrophic lateral sclerosis, multiple sclerosis, traumatic and vascular acute neural injury, epilepsy, and inflammatory bowel disease, alteration of S100B levels correlates with the occurrence of clinical and/or toxic parameters. In general, overexpression/administration of S100B worsens the clinical presentation, whereas deletion/inactivation of the protein contributes to the amelioration of the symptoms. Thus, the S100B protein may be proposed as a common pathogenic factor in different disorders, sharing different symptoms and etiologies but appearing to share some common pathogenic processes reasonably attributable to neuroinflammation.}, } @article {pmid37298512, year = {2023}, author = {Guo, Z}, title = {Ganglioside GM1 and the Central Nervous System.}, journal = {International journal of molecular sciences}, volume = {24}, number = {11}, pages = {}, pmid = {37298512}, issn = {1422-0067}, support = {R35 GM131686/GM/NIGMS NIH HHS/United States ; R35GM131686/NH/NIH HHS/United States ; }, mesh = {Humans ; *G(M1) Ganglioside/metabolism ; *Gangliosidosis, GM1 ; Central Nervous System/metabolism ; Brain/metabolism ; Glycosphingolipids/metabolism ; }, abstract = {GM1 is one of the major glycosphingolipids (GSLs) on the cell surface in the central nervous system (CNS). Its expression level, distribution pattern, and lipid composition are dependent upon cell and tissue type, developmental stage, and disease state, which suggests a potentially broad spectrum of functions of GM1 in various neurological and neuropathological processes. The major focus of this review is the roles that GM1 plays in the development and activities of brains, such as cell differentiation, neuritogenesis, neuroregeneration, signal transducing, memory, and cognition, as well as the molecular basis and mechanisms for these functions. Overall, GM1 is protective for the CNS. Additionally, this review has also examined the relationships between GM1 and neurological disorders, such as Alzheimer's disease, Parkinson's disease, GM1 gangliosidosis, Huntington's disease, epilepsy and seizure, amyotrophic lateral sclerosis, depression, alcohol dependence, etc., and the functional roles and therapeutic applications of GM1 in these disorders. Finally, current obstacles that hinder more in-depth investigations and understanding of GM1 and the future directions in this field are discussed.}, } @article {pmid37298129, year = {2023}, author = {Molinaro, P and Sanguigno, L and Casamassa, A and Valsecchi, V and Sirabella, R and Pignataro, G and Annunziato, L and Formisano, L}, title = {Emerging Role of DREAM in Healthy Brain and Neurological Diseases.}, journal = {International journal of molecular sciences}, volume = {24}, number = {11}, pages = {}, pmid = {37298129}, issn = {1422-0067}, support = {PE0000006//Ministry of Education, Universities and Research/ ; PE0000012//Ministry of Education, Universities and Research/ ; CN00000041//Ministry of Education, Universities and Research/ ; 2017JL8SRX//Ministry of Education, Universities and Research/ ; 20173EAZ2Z//Ministry of Education, Universities and Research/ ; 2017WJZ9W9//Ministry of Education, Universities and Research/ ; }, mesh = {*Kv Channel-Interacting Proteins/metabolism ; *Repressor Proteins/genetics ; Brain/metabolism ; Dynorphins/metabolism ; Cell Nucleus/metabolism ; }, abstract = {The downstream regulatory element antagonist modulator (DREAM) is a multifunctional Ca[2+]-sensitive protein exerting a dual mechanism of action to regulate several Ca[2+]-dependent processes. Upon sumoylation, DREAM enters in nucleus where it downregulates the expression of several genes provided with a consensus sequence named dream regulatory element (DRE). On the other hand, DREAM could also directly modulate the activity or the localization of several cytosolic and plasma membrane proteins. In this review, we summarize recent advances in the knowledge of DREAM dysregulation and DREAM-dependent epigenetic remodeling as a central mechanism in the progression of several diseases affecting central nervous system, including stroke, Alzheimer's and Huntington's diseases, amyotrophic lateral sclerosis, and neuropathic pain. Interestingly, DREAM seems to exert a common detrimental role in these diseases by inhibiting the transcription of several neuroprotective genes, including the sodium/calcium exchanger isoform 3 (NCX3), brain-derived neurotrophic factor (BDNF), pro-dynorphin, and c-fos. These findings lead to the concept that DREAM might represent a pharmacological target to ameliorate symptoms and reduce neurodegenerative processes in several pathological conditions affecting central nervous system.}, } @article {pmid37297781, year = {2023}, author = {Gentili, D and Deiana, G and Chessa, V and Calabretta, A and Marras, E and Solinas, C and Gugliotta, C and Azara, A}, title = {Quality of Life in Amyotrophic Lateral Sclerosis Patients and Care Burden of Caregivers in Sardinia during COVID-19 Pandemic.}, journal = {Healthcare (Basel, Switzerland)}, volume = {11}, number = {11}, pages = {}, pmid = {37297781}, issn = {2227-9032}, abstract = {Amyotrophic Lateral Sclerosis (ALS) is a rare neurogenerative disorder whose median survival ranges from 2 to 4 years after symptomatic onset. Therefore, the global Quality of Life (QoL) assessment in these patients should be carefully evaluated to guarantee an adequate care level, particularly during the COVID-19 pandemic period, given the increased social isolation and the pressure on healthcare services. Caregiving has been recognized as an important source of physical and psychological burden, with a possible QoL impairment. The purpose of this study was to evaluate the QoL of ALS patients and the burden of their caregivers across Sardinia, Italy. The ALS Specific QoL Instrument-Short Form (ALSSQOL-SF) and the Zarit Burden Inventory (ZBI) tools were used to assess patient's QoL and the burden on their caregivers, respectively. The questionnaires were supplemented with items specific for the COVID-19 period. Sixty-six family units of patients with advanced ALS were interviewed between June and August 2021 across Sardinia. Patients' psychological and social well-being were found to significantly affect the patients' QoL, regardless of their physical condition. In addition, the caregiver burden resulted as being inversely proportional to the patient's perceived QoL. Lack of adequate psychological support was reported among the caregivers during the emergency period. Providing adequate psychological and social support might be useful to improve QoL in middle and late stages of ALS patients and to decrease caregivers' perceived home care burden.}, } @article {pmid37296644, year = {2023}, author = {Tzeplaeff, L and Wilfling, S and Requardt, MV and Herdick, M}, title = {Current State and Future Directions in the Therapy of ALS.}, journal = {Cells}, volume = {12}, number = {11}, pages = {}, pmid = {37296644}, issn = {2073-4409}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy ; Riluzole/therapeutic use ; Motor Neurons/pathology ; Biomarkers ; Disease Progression ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative disorder affecting upper and lower motor neurons, with death resulting mainly from respiratory failure three to five years after symptom onset. As the exact underlying causative pathological pathway is unclear and potentially diverse, finding a suitable therapy to slow down or possibly stop disease progression remains challenging. Varying by country Riluzole, Edaravone, and Sodium phenylbutyrate/Taurursodiol are the only drugs currently approved in ALS treatment for their moderate effect on disease progression. Even though curative treatment options, able to prevent or stop disease progression, are still unknown, recent breakthroughs, especially in the field of targeting genetic disease forms, raise hope for improved care and therapy for ALS patients. In this review, we aim to summarize the current state of ALS therapy, including medication as well as supportive therapy, and discuss the ongoing developments and prospects in the field. Furthermore, we highlight the rationale behind the intense research on biomarkers and genetic testing as a feasible way to improve the classification of ALS patients towards personalized medicine.}, } @article {pmid37296623, year = {2023}, author = {Kandhavivorn, W and Glaß, H and Herrmannsdörfer, T and Böckers, TM and Uhlarz, M and Gronemann, J and Funk, RHW and Pietzsch, J and Pal, A and Hermann, A}, title = {Restoring Axonal Organelle Motility and Regeneration in Cultured FUS-ALS Motoneurons through Magnetic Field Stimulation Suggests an Alternative Therapeutic Approach.}, journal = {Cells}, volume = {12}, number = {11}, pages = {}, pmid = {37296623}, issn = {2073-4409}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism ; Motor Neurons/pathology ; Axons/metabolism ; Organelles/metabolism ; Magnetic Fields ; RNA-Binding Protein FUS/genetics/metabolism ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a devastating motoneuron disease characterized by sustained loss of neuromuscular junctions, degenerating corticospinal motoneurons and rapidly progressing muscle paralysis. Motoneurons have unique features, essentially a highly polarized, lengthy architecture of axons, posing a considerable challenge for maintaining long-range trafficking routes for organelles, cargo, mRNA and secretion with a high energy effort to serve crucial neuronal functions. Impaired intracellular pathways implicated in ALS pathology comprise RNA metabolism, cytoplasmic protein aggregation, cytoskeletal integrity for organelle trafficking and maintenance of mitochondrial morphology and function, cumulatively leading to neurodegeneration. Current drug treatments only have marginal effects on survival, thereby calling for alternative ALS therapies. Exposure to magnetic fields, e.g., transcranial magnetic stimulations (TMS) on the central nervous system (CNS), has been broadly explored over the past 20 years to investigate and improve physical and mental activities through stimulated excitability as well as neuronal plasticity. However, studies of magnetic treatments on the peripheral nervous system are still scarce. Thus, we investigated the therapeutic potential of low frequency alternating current magnetic fields on cultured spinal motoneurons derived from induced pluripotent stem cells of FUS-ALS patients and healthy persons. We report a remarkable restoration induced by magnetic stimulation on axonal trafficking of mitochondria and lysosomes and axonal regenerative sprouting after axotomy in FUS-ALS in vitro without obvious harmful effects on diseased and healthy neurons. These beneficial effects seem to derive from improved microtubule integrity. Thus, our study suggests the therapeutic potential of magnetic stimulations in ALS, which awaits further exploration and validation in future long-term in vivo studies.}, } @article {pmid37296572, year = {2023}, author = {Dučić, T and Koch, JC}, title = {Synchrotron-Based Fourier-Transform Infrared Micro-Spectroscopy of Cerebrospinal Fluid from Amyotrophic Lateral Sclerosis Patients Reveals a Unique Biomolecular Profile.}, journal = {Cells}, volume = {12}, number = {11}, pages = {}, pmid = {37296572}, issn = {2073-4409}, mesh = {Adult ; Humans ; *Amyotrophic Lateral Sclerosis/metabolism ; Spectroscopy, Fourier Transform Infrared ; *Neurodegenerative Diseases ; Synchrotrons ; Lipids ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease, with the most common adult-onset neurodegenerative disorder affecting motoneurons. Although disruptions in macromolecular conformation and homeostasis have been described in association with ALS, the underlying pathological mechanisms are still not completely understood, and unambiguous biomarkers are lacking. Fourier Transform Infrared Spectroscopy (FTIR) of cerebrospinal fluid (CSF) is appealing to extensive interest due to its potential to resolve biomolecular conformation and content, as this approach offers a non-invasive, label-free identification of specific biologically relevant molecules in a few microliters of CSF sample. Here, we analyzed the CSF of 33 ALS patients compared to 32 matched controls using FTIR spectroscopy and multivariate analysis and demonstrated major differences in the molecular contents. A significant change in the conformation and concentration of RNA is demonstrated. Moreover, significantly increased glutamate and carbohydrates are found in ALS. Moreover, key markers of lipid metabolism are strongly altered; specifically, we find a decrease in unsaturated lipids and an increase in peroxidation of lipids in ALS, whereas the total amount of lipids compared to proteins is reduced. Our study demonstrates that FTIR characterization of CSF could represent a powerful tool for ALS diagnosis and reveals central features of ALS pathophysiology.}, } @article {pmid37296571, year = {2023}, author = {Valori, CF and Sulmona, C and Brambilla, L and Rossi, D}, title = {Astrocytes: Dissecting Their Diverse Roles in Amyotrophic Lateral Sclerosis and Frontotemporal Dementia.}, journal = {Cells}, volume = {12}, number = {11}, pages = {}, pmid = {37296571}, issn = {2073-4409}, mesh = {Animals ; *Astrocytes ; *Frontotemporal Dementia ; *Amyotrophic Lateral Sclerosis ; }, abstract = {Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are fatal neurodegenerative disorders often co-occurring in the same patient, a feature that suggests a common origin of the two diseases. Consistently, pathological inclusions of the same proteins as well as mutations in the same genes can be identified in both ALS/FTD. Although many studies have described several disrupted pathways within neurons, glial cells are also regarded as crucial pathogenetic contributors in ALS/FTD. Here, we focus our attention on astrocytes, a heterogenous population of glial cells that perform several functions for optimal central nervous system homeostasis. Firstly, we discuss how post-mortem material from ALS/FTD patients supports astrocyte dysfunction around three pillars: neuroinflammation, abnormal protein aggregation, and atrophy/degeneration. Furthermore, we summarize current attempts at monitoring astrocyte functions in living patients using either novel imaging strategies or soluble biomarkers. We then address how astrocyte pathology is recapitulated in animal and cellular models of ALS/FTD and how we used these models both to understand the molecular mechanisms driving glial dysfunction and as platforms for pre-clinical testing of therapeutics. Finally, we present the current clinical trials for ALS/FTD, restricting our discussion to treatments that modulate astrocyte functions, directly or indirectly.}, } @article {pmid37296379, year = {2023}, author = {Piccoli, T and Castro, F and La Bella, V and Meraviglia, S and Di Simone, M and Salemi, G and Dieli, F and Spataro, R}, title = {Role of the immune system in amyotrophic lateral sclerosis. Analysis of the natural killer cells and other circulating lymphocytes in a cohort of ALS patients.}, journal = {BMC neurology}, volume = {23}, number = {1}, pages = {222}, pmid = {37296379}, issn = {1471-2377}, mesh = {Humans ; Male ; *Amyotrophic Lateral Sclerosis/complications ; Disease Progression ; Killer Cells, Natural ; }, abstract = {AIMS: Neuroinflammation might be involved in the degeneration and progression of Amyotrophic Lateral Sclerosis (ALS). Here, we studied the role of the circulating lymphocytes in ALS, in particular the NK cells. We focused on the relationship between blood lymphocytes, ALS clinical subtype and disease severity.

SUBJECTS AND METHODS: Blood samples were collected from 92 patients with sporadic ALS, 21 patients with Primary Lateral Sclerosis (PLS) and 37 patients affected by primary progressive multiple sclerosis (PPMS) with inactive plaques. Blood was taken from ALS and controls at the time of diagnosis/referral. Circulating lymphocytes were analyzed by flow cytometry with specific antibodies. Values were expressed as absolute number (n°/µl) of viable lymphocytes subpopulations in ALS were compared with controls. Multivariable analysis was made using site of onset, gender changes in ALSFRS-R and disease progression rate (calculated as ΔFS score).

RESULTS: Age at onset was 65y (58-71) in ALS (spinal 67.4%; bulbar, 32.6%), 57y (48-78) in PLS and 56y (44-68) PPMS. Absolute blood levels of the lymphocytes in the different cohorts were within normal range. Furthermore, while levels of lymphocytes T and B were not different between disease groups, NK cells were increased in the ALS cohort (ALS = 236 [158-360] vs. Controls = 174[113-240], p < 0.001). In ALS, blood levels of NK cells were not related with the main clinical-demographic variables, including the rate of disease progression. Multivariable analysis suggested that male gender and bulbar onset were independently associated with a risk of high blood NK cells levels.

CONCLUSIONS: We show that blood NK cells are selectively increased in ALS, though their level appear unaffected in patients with an estimated rapidly progressing disease. Being of a male gender and with a bulbar onset seems to confer higher susceptibility to have increased NK lymphocytes levels at diagnosis/referral. Our experiments provides a further clear-cut evidence of the role of the NK lymphocytes as a significant player in ALS pathogenesis.}, } @article {pmid37295966, year = {2023}, author = {Alves, I and Gromicho, M and Oliveira Santos, M and Pinto, S and Pronto-Laborinho, A and Swash, M and de Carvalho, M}, title = {Demographic changes in a large motor neuron disease cohort in Portugal: a 27 year experience.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {}, number = {}, pages = {1-11}, doi = {10.1080/21678421.2023.2220747}, pmid = {37295966}, issn = {2167-9223}, abstract = {Objective: Motor Neuron Diseases (MND) have a large clinical spectrum, being the most common amyotrophic lateral sclerosis (ALS) but there is significant clinical heterogeneity. Our goal was to investigate this heterogeneity and any potential changes during a long period. Methods: We performed a retrospective cohort study among a large Portuguese cohort of MND patients (n = 1550) and investigated changing patterns in clinical and demographic characteristics over the 27-year period of our database. With that aim, patients were divided into three 9-year groups according to the date of their first visit to our unit: P1, 1994-2002; P2, 2003-2011; P3, 2012-2020. Results: The overall cohort's clinical and demographic characteristics are consistent with clinical experience, but our findings point to gradual changes over time. Time pattern analysis revealed statistically significant differences in the distribution of clinical phenotypes, the average age of onset, diagnostic delay, the proportin of patients using respiratory support with noninvasive ventilation (NIV), time to NIV, and survival. Across time, in the overall cohort, we found an increasing age at onset (p = 0.029), a decrease of two months in diagnostic delay (p < 0.001) and a higher relative frequency of progressive muscular atrophy patients. For ALS patients with spinal onset, from P1 to P2, there was a more widespread (54.8% vs 69.4%, p = 0.005) and earlier (36.9 vs 27.2 months, p = 0.05) use of NIV and a noteworthy 13-month increase in median survival (p = 0.041). Conclusions: Our results probably reflect better comprehensive care, and they are relevant for future studies exploring the impact of new treatments on ALS patients.}, } @article {pmid37295429, year = {2023}, author = {Boeynaems, S and Dorone, Y and Zhuang, Y and Shabardina, V and Huang, G and Marian, A and Kim, G and Sanyal, A and Şen, NE and Griffith, D and Docampo, R and Lasker, K and Ruiz-Trillo, I and Auburger, G and Holehouse, AS and Kabashi, E and Lin, Y and Gitler, AD}, title = {Poly(A)-binding protein is an ataxin-2 chaperone that regulates biomolecular condensates.}, journal = {Molecular cell}, volume = {83}, number = {12}, pages = {2020-2034.e6}, pmid = {37295429}, issn = {1097-4164}, support = {P30 NS069375/NS/NINDS NIH HHS/United States ; P01 AG019724/AG/NIA NIH HHS/United States ; R21 AI140421/AI/NIAID NIH HHS/United States ; U54 NS123743/NS/NINDS NIH HHS/United States ; R35 NS097263/NS/NINDS NIH HHS/United States ; }, mesh = {Humans ; *Ataxin-2/genetics ; Poly(A)-Binding Protein I ; *Neurodegenerative Diseases/metabolism ; Biomolecular Condensates ; }, abstract = {Biomolecular condensation underlies the biogenesis of an expanding array of membraneless assemblies, including stress granules (SGs), which form under a variety of cellular stresses. Advances have been made in understanding the molecular grammar of a few scaffold proteins that make up these phases, but how the partitioning of hundreds of SG proteins is regulated remains largely unresolved. While investigating the rules that govern the condensation of ataxin-2, an SG protein implicated in neurodegenerative disease, we unexpectedly identified a short 14 aa sequence that acts as a condensation switch and is conserved across the eukaryote lineage. We identify poly(A)-binding proteins as unconventional RNA-dependent chaperones that control this regulatory switch. Our results uncover a hierarchy of cis and trans interactions that fine-tune ataxin-2 condensation and reveal an unexpected molecular function for ancient poly(A)-binding proteins as regulators of biomolecular condensate proteins. These findings may inspire approaches to therapeutically target aberrant phases in disease.}, } @article {pmid37295193, year = {2023}, author = {Yamashita, S and Tawara, N and Hara, K and Ueda, M}, title = {Gender differences in clinical features at the initial examination of late-onset amyotrophic lateral sclerosis.}, journal = {Journal of the neurological sciences}, volume = {451}, number = {}, pages = {120697}, doi = {10.1016/j.jns.2023.120697}, pmid = {37295193}, issn = {1878-5883}, mesh = {Male ; Female ; Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/epidemiology ; Retrospective Studies ; *Neurodegenerative Diseases ; Sex Factors ; Motor Neurons ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that mainly affects motor neurons in the brain and spinal cord. With the advent of aging societies, the proportion of elderly patients with ALS is expected to increase.

METHODS: We retrospectively compared the clinical characteristics at the initial examination of patients with onset of ALS at age 74 years or younger (early onset) and those aged 75 years or older at onset (late-onset) at a single regional ALS diagnostic center in Japan.

RESULTS: The phenotype of late-onset ALS differed between males and females, with late-onset females having more bulbar-onset ALS and significantly lower body mass index, late-onset males having more frequent bulbar and respiratory symptoms at the initial examination, and significantly lower forced vital capacity at the initial examination in both groups compared to early onset patients.

CONCLUSION: For late-onset patients, maintenance of skeletal muscle mass by early intervention for bulbar and respiratory symptoms may be useful for prolonging survival; however, a prospective analysis is warranted.}, } @article {pmid37294668, year = {2023}, author = {Sato, K and Farquhar, CE and Rodriguez, J and Pentelute, BL}, title = {Automated Fast-Flow Synthesis of Chromosome 9 Open Reading Frame 72 Dipeptide Repeat Proteins.}, journal = {Journal of the American Chemical Society}, volume = {145}, number = {24}, pages = {12992-12997}, doi = {10.1021/jacs.3c02285}, pmid = {37294668}, issn = {1520-5126}, mesh = {Humans ; *Dipeptides/chemistry ; C9orf72 Protein/genetics/metabolism ; Open Reading Frames ; *Proteins/chemistry ; Glycine ; Alanine ; Proline ; Arginine/genetics ; Chromosomes, Human, Pair 9/metabolism ; }, abstract = {An expansion of the hexanucleotide (GGGGCC) repeat sequence in chromosome 9 open frame 72 (c9orf72) is the most common genetic mutation in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The mutation leads to the production of toxic dipeptide repeat proteins (DPRs) that induce neurodegeneration. However, the fundamental physicochemical properties of DPRs remain largely unknown due to their limited availability. Here, we synthesized the c9orf72 DPRs poly-glycine-arginine (poly-GR), poly-proline-arginine (poly-PR), poly-glycine-proline (poly-GP), poly-proline-alanine (poly-PA), and poly-glycine-alanine (poly-GA) using automated fast-flow peptide synthesis (AFPS) and achieved single-domain chemical synthesis of proteins with up to 200 amino acids. Circular dichroism spectroscopy of the synthetic DPRs revealed that proline-containing poly-PR, poly-GP, and poly-PA could adopt polyproline II-like helical secondary structures. In addition, structural analysis by size-exclusion chromatography indicated that longer poly-GP and poly-PA might aggregate. Furthermore, cell viability assays showed that human neuroblastoma cells cultured with poly-GR and poly-PR with longer repeat lengths resulted in reduced cell viability, while poly-GP and poly-PA did not, thereby reproducing the cytotoxic property of endogenous DPRs. This research demonstrates the potential of AFPS to synthesize low-complexity peptides and proteins necessary for studying their pathogenic mechanisms and constructing disease models.}, } @article {pmid37294189, year = {2023}, author = {Pegat, A and Bernard, E}, title = {Immunoglobulin light-chain amyloidosis mimicking bulbar amyotrophic lateral sclerosis.}, journal = {Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis}, volume = {30}, number = {3}, pages = {346-347}, doi = {10.1080/13506129.2022.2163891}, pmid = {37294189}, issn = {1744-2818}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis ; *Immunoglobulin Light-chain Amyloidosis/diagnosis ; Tongue Diseases/diagnosis ; }, } @article {pmid37293667, year = {2023}, author = {Manera, U and Grassano, M and Matteoni, E and Bombaci, A and Vasta, R and Palumbo, F and Torrieri, MC and Cugnasco, P and Moglia, C and Canosa, A and Chiò, A and Calvo, A}, title = {Serum chloride as a respiratory failure marker in amyotrophic lateral sclerosis.}, journal = {Frontiers in aging neuroscience}, volume = {15}, number = {}, pages = {1188827}, pmid = {37293667}, issn = {1663-4365}, abstract = {Respiratory failure is the most common cause of death in patients with amyotrophic lateral sclerosis (ALS) and occurs with great variability among patients according to different phenotypic features. Early predictors of respiratory failure in ALS are important to start non-invasive ventilation (NIV). Venous serum chloride values correlate with carbonate (HCO3-) blood levels and reflect metabolic compensation of respiratory acidosis. Despite its wide availability and low cost, few data on serum chloride as a prognostic marker exist in ALS literature. In the present study, we evaluated serum chloride values at diagnosis as prognostic biomarkers for overall survival and NIV adaptation in a retrospective center-based cohort of ALS patients. We collected all ALS patients with serum chloride assessment at diagnosis, identified through the Piemonte and Valle d'Aosta Register for ALS, evaluating the correlations among serum chloride, clinical features, and other serum biomarkers. Thereafter, time-to-event analysis was modeled to predict overall survival and NIV start. We found a significant correlation between serum chloride and inflammatory status markers, serum sodium, forced vital capacity (FVC), ALS functional rating scale-revised (ALSFRS-R) item 10 and 11, age at diagnosis, and weight loss. Time-to-event analysis confirmed both in univariate analysis and after multiple confounders' adjustment that serum chloride value at diagnosis significantly influenced survival and time to NIV start. According to our analysis, based on a large ALS cohort, we found that serum chloride analyzed at diagnosis is a low-cost marker of impending respiratory decompensation. In our opinion, it should be added among the serum prognostic biomarkers that are able to stratify patients into different prognostic categories even when performed in the early phases of the disease.}, } @article {pmid37293291, year = {2023}, author = {Dou, J and Bakulski, K and Guo, K and Hur, J and Zhao, L and Saez-Atienzar, S and Stark, A and Chia, R and García-Redondo, A and Rojas-Garcia, R and Vázquez Costa, JF and Fernandez Santiago, R and Bandres-Ciga, S and Gómez-Garre, P and Periñán, MT and Mir, P and Pérez-Tur, J and Cardona, F and Menendez-Gonzalez, M and Riancho, J and Borrego-Hernández, D and Galán-Dávila, L and Infante Ceberio, J and Pastor, P and Paradas, C and Dols-Icardo, O and Traynor, BJ and Feldman, EL and Goutman, SA and , }, title = {Cumulative Genetic Score and C9orf72 Repeat Status Independently Contribute to Amyotrophic Lateral Sclerosis Risk in 2 Case-Control Studies.}, journal = {Neurology. Genetics}, volume = {9}, number = {4}, pages = {e200079}, pmid = {37293291}, issn = {2376-7839}, support = {P30 ES017885/ES/NIEHS NIH HHS/United States ; R01 ES030049/ES/NIEHS NIH HHS/United States ; R01 NS127188/NS/NINDS NIH HHS/United States ; R01 TS000289/TS/ATSDR CDC HHS/United States ; }, abstract = {BACKGROUND AND OBJECTIVES: Most patients with amyotrophic lateral sclerosis (ALS) lack a monogenic mutation. This study evaluates ALS cumulative genetic risk in an independent Michigan and Spanish replication cohort using polygenic scores.

METHODS: Participant samples from University of Michigan were genotyped and assayed for the chromosome 9 open reading frame 72 hexanucleotide expansion. Final cohort size was 219 ALS and 223 healthy controls after genotyping and participant filtering. Polygenic scores excluding the C9 region were generated using an independent ALS genome-wide association study (20,806 cases, 59,804 controls). Adjusted logistic regression and receiver operating characteristic curves evaluated the association and classification between polygenic scores and ALS status, respectively. Population attributable fractions and pathway analyses were conducted. An independent Spanish study sample (548 cases, 2,756 controls) was used for replication.

RESULTS: Polygenic scores constructed from 275 single-nucleotide variation (SNV) had the best model fit in the Michigan cohort. An SD increase in ALS polygenic score associated with 1.28 (95% CI 1.04-1.57) times higher odds of ALS with area under the curve of 0.663 vs a model without the ALS polygenic score (p value = 1 × 10[-6]). The population attributable fraction of the highest 20th percentile of ALS polygenic scores, relative to the lowest 80th percentile, was 4.1% of ALS cases. Genes annotated to this polygenic score enriched for important ALS pathomechanisms. Meta-analysis with the Spanish study, using a harmonized 132 single nucleotide variation polygenic score, yielded similar logistic regression findings (odds ratio: 1.13, 95% CI 1.04-1.23).

DISCUSSION: ALS polygenic scores can account for cumulative genetic risk in populations and reflect disease-relevant pathways. If further validated, this polygenic score will inform future ALS risk models.}, } @article {pmid37292457, year = {2023}, author = {Davies, JC and Dharmadasa, T and Thompson, AG and Edmond, EC and Yoganathan, K and Gao, J and Talbot, K and Turner, MR}, title = {Limited value of serum neurofilament light chain in diagnosing amyotrophic lateral sclerosis.}, journal = {Brain communications}, volume = {5}, number = {3}, pages = {fcad163}, pmid = {37292457}, issn = {2632-1297}, support = {MR/T006927/1/MRC_/Medical Research Council/United Kingdom ; TURNER/OCT18/989-797/MNDA_/Motor Neurone Disease Association/United Kingdom ; }, abstract = {A biomarker specific for the diagnosis of amyotrophic lateral sclerosis must be sensitive across a spectrum of clinical heterogeneity. Neurofilament light chain levels in amyotrophic lateral sclerosis correlate with the rate of disability progression. Previous attempts to establish a diagnostic role for neurofilament light chain have been limited to comparison with healthy individuals or controls with alternative diagnoses unlikely to be confused with amyotrophic lateral sclerosis in real-world clinical practice. In a tertiary amyotrophic lateral sclerosis referral clinic, at first visit, serum was taken for neurofilament light chain measurement after prospectively recording the clinical diagnosis as 'amyotrophic lateral sclerosis', 'primary lateral sclerosis', 'alternative' or 'currently uncertain'. Of 133 referrals, 93 patients were diagnosed with amyotrophic lateral sclerosis (median neurofilament light chain 218.1 pg/ml, interquartile range 130.7-311.9), three primary lateral sclerosis (65.6, 51.5-106.9) and 19 alternative diagnoses (45.2, 13.5-71.9) at first visit. Of 18 initially uncertain diagnoses, eight were subsequently diagnosed with amyotrophic lateral sclerosis (98.5, 45.3-300.1). Neurofilament light chain ≥110.9 pg/ml had a positive predictive value of 0.92 for amyotrophic lateral sclerosis; <110.9 pg/ml had a negative predictive value of 0.48. In a specialized clinic, neurofilament light chain is largely confirmatory to clinical judgement in diagnosing amyotrophic lateral sclerosis and has limited ability to exclude alternative diagnoses. The current, important, value of neurofilament light chain is its potential to stratify patients with amyotrophic lateral sclerosis by disease activity and as a biomarker in therapeutic trials.}, } @article {pmid37292026, year = {2023}, author = {Poletti, B and Aiello, EN and La Tona, A and Solca, F and Torre, S and Colombo, E and Maranzano, A and Morelli, C and Doretti, A and Verde, F and Monti, A and Brugnera, A and Compare, A and Ferrucci, R and Barbieri, S and Mameli, F and Priori, A and Pravettoni, G and Silani, V and Ticozzi, N}, title = {Single task-level, 2SD-based cutoffs for the Italian version of the Edinburgh Cognitive and Behavioral ALS screen (ECAS).}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {}, number = {}, pages = {1-4}, doi = {10.1080/21678421.2023.2220746}, pmid = {37292026}, issn = {2167-9223}, abstract = {The present study aimed at deriving, by means of a traditional "2 standard deviation-based" (2SD) approach, single task-level cutoffs for the Italian version of the Edinburgh Cognitive and Behavioral ALS Screen (ECAS). Cutoffs were derived - as M-2*SD - from the sample of healthy participants (HPs) included within 2016 Poletti et al.'s normative study - N = 248; 104 males; age: 57.8 ± 10.6; education: 14.1 ± 4.6 - separately for the four, original demographic classes: 1) education <14 years and age ≤60 years; 2) education <14 years and age >60 years; 3) education ≥14 years and age ≤60 years; 4) education ≥14 years and age >60 years. The prevalence of deficits on each task was then estimated within a cohort of N = 377 amyotrophic lateral sclerosis (ALS) patients without dementia. The distribution of abnormal performance prevalences was overall consistent with the cognitive phenotype of ALS. In conclusion, the single task-level cutoffs herewith provided for the Italian version of the ECAS, which complement those already available within Poletti et al.'s normative framework, will help better profile Italian ALS patients' cognitive phenotype within both clinical and research settings.}, } @article {pmid37291830, year = {2023}, author = {Ibrahim, NM and Jagota, P and Pal, PK and Bhidayasiri, R and Lim, SY and Ugawa, Y and Aldaajani, Z and Jeon, B and Fujioka, S and Lee, JY and Kukkle, PL and Shang, H and Phokaewvarangkul, O and Diesta, C and Shambetova, C and Lin, CH}, title = {Historical and More Common Nongenetic Movement Disorders From Asia.}, journal = {Journal of movement disorders}, volume = {16}, number = {3}, pages = {248-260}, pmid = {37291830}, issn = {2005-940X}, abstract = {Nongenetic movement disorders are common throughout the world. The movement disorders encountered may vary depending on the prevalence of certain disorders across various geographical regions. In this paper, we review historical and more common nongenetic movement disorders in Asia. The underlying causes of these movement disorders are diverse and include, among others, nutritional deficiencies, toxic and metabolic causes, and cultural Latah syndrome, contributed by geographical, economic, and cultural differences across Asia. The industrial revolution in Japan and Korea has led to diseases related to environmental toxin poisoning, such as Minamata disease and β-fluoroethyl acetate-associated cerebellar degeneration, respectively, while religious dietary restriction in the Indian subcontinent has led to infantile tremor syndrome related to vitamin B12 deficiency. In this review, we identify the salient features and key contributing factors in the development of these disorders.}, } @article {pmid37291782, year = {2024}, author = {Dai, S and Qiu, L and Veeraraghavan, VP and Sheu, CL and Mony, U}, title = {Advances in iPSC Technology in Neural Disease Modeling, Drug Screening, and Therapy.}, journal = {Current stem cell research & therapy}, volume = {19}, number = {6}, pages = {809-819}, doi = {10.2174/1574888X18666230608105703}, pmid = {37291782}, issn = {2212-3946}, mesh = {Humans ; *Induced Pluripotent Stem Cells/cytology ; *Drug Evaluation, Preclinical/methods ; Animals ; *Neurodegenerative Diseases/therapy ; Cell- and Tissue-Based Therapy/methods ; Cell Differentiation ; Disease Models, Animal ; }, abstract = {Neurodegenerative disorders (NDs) including Alzheimer's Disease, Parkinson's Disease, Amyotrophic Lateral Sclerosis (ALS), and Huntington's disease are all incurable and can only be managed with drugs for the associated symptoms. Animal models of human illnesses help to advance our understanding of the pathogenic processes of diseases. Understanding the pathogenesis as well as drug screening using appropriate disease models of neurodegenerative diseases (NDs) are vital for identifying novel therapies. Human-derived induced pluripotent stem cell (iPSC) models can be an efficient model to create disease in a dish and thereby can proceed with drug screening and identifying appropriate drugs. This technology has many benefits, including efficient reprogramming and regeneration potential, multidirectional differentiation, and the lack of ethical concerns, which open up new avenues for studying neurological illnesses in greater depth. The review mainly focuses on the use of iPSC technology in neuronal disease modeling, drug screening, and cell therapy.}, } @article {pmid37290723, year = {2023}, author = {Lu, Y and Wang, JT and Li, N and Zhu, X and Li, Y and Bansal, S and Wang, Y and Al-Jamal, KT}, title = {Intranasal administration of edaravone nanoparticles improves its stability and brain bioavailability.}, journal = {Journal of controlled release : official journal of the Controlled Release Society}, volume = {359}, number = {}, pages = {257-267}, doi = {10.1016/j.jconrel.2023.06.001}, pmid = {37290723}, issn = {1873-4995}, mesh = {Animals ; Mice ; Administration, Intranasal ; *Amyotrophic Lateral Sclerosis/drug therapy ; Biological Availability ; Brain/metabolism ; Chromatography, Liquid ; Drug Carriers/chemistry ; Drug Delivery Systems ; *Edaravone/administration & dosage/pharmacokinetics ; Hydrogen Peroxide/metabolism ; *Nanoparticles/administration & dosage ; Particle Size ; Polylactic Acid-Polyglycolic Acid Copolymer/metabolism ; Tandem Mass Spectrometry ; Tissue Distribution ; Cell Line ; }, abstract = {The clinical application of EDV, a potent antioxidant drug approved for amyotrophic lateral sclerosis (ALS), is limited by its short biological half-life and poor water solubility necessitating hospitalization during intravenous infusion. Nanotechnology-based drug delivery constitutes a powerful tool through inferring drug stability and targeted drug delivery improving drug bioavailability at the diseased site. Nose-to-brain drug delivery offers direct access to the brain bypassing the blood brain barrier and reducing systemic biodistribution. In this study, we designed EDV-loaded poly(lactic-co-glycolic acid) (PLGA)-based polymeric nanoparticles (NP-EDV) for intranasal administration. NPs were formulated by the nanoprecipitation method. Morphology, EDV loading, physicochemical properties, shelf-life stability, in vitro release and pharmacokinetic assessment in mice were conducted. EDV was efficiently loaded into ∼90 nm NPs, stable up to 30 days of storage, at ∼3% drug loading. NP-EDV reduced H2O2-induced oxidative stress toxicity in mouse microglial cell line BV-2. Optical imaging and ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) showed that intranasal delivery of NP-EDV offered higher and more sustained brain uptake of EDV compared to intravenous administration. This study is the first of its kind to develop an ALS drug in a nanoparticulate formulation for nose-to-brain delivery raising hope to ALS patients where currently treatment options are limited to two clinically approved drugs only.}, } @article {pmid37290686, year = {2023}, author = {Liu, Y and Ding, M and Pan, S and Zhou, R and Yao, J and Fu, R and Yu, H and Lu, Z}, title = {MicroRNA-23a-3p Is Upregulated in Plasma Exosomes of Bulbar-onset ALS Patients and Targets ERBB4.}, journal = {Neuroscience}, volume = {524}, number = {}, pages = {65-78}, doi = {10.1016/j.neuroscience.2023.05.030}, pmid = {37290686}, issn = {1873-7544}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/pathology ; *Exosomes/metabolism ; *Neurodegenerative Diseases/metabolism ; *MicroRNAs/metabolism ; Apoptosis ; Receptor, ErbB-4/metabolism ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease related to the progressive death of motor neurons. Understanding the pathogenesis of ALS continues to provide considerable challenges. Bulbar-onset ALS involves faster functional loss and shorter survival time than spinal cord-onset ALS. However, debate is ongoing regarding typical plasma miRNA changes in ALS patients with bulbar onset. Exosomal miRNAs have not yet been described as a tool for bulbar-onset ALS diagnosis or prognosis prediction. In this study, candidate exosomal miRNAs were identified by small RNA sequencing using samples from patients with bulbar-onset ALS and healthy controls. Potential pathogenic mechanisms were identified through enrichment analysis of target genes for differential miRNAs. Expression of miR-16-5p, miR-23a-3p, miR-22-3p, and miR-93-5p was significantly up-regulated in plasma exosomes from bulbar-onset ALS patients compared with healthy control subjects. Among them, miR-16-5p and miR-23a-3p were significantly lower in spinal-onset ALS patients than those with bulbar-onset. Furthermore, up-regulation of miR-23a-3p in motor neuron-like NSC-34 cells promoted apoptosis and inhibited cell viability. This miRNA was found to directly target ERBB4 and regulate the AKT/GSK3β pathway. Collectively, the above miRNAs and their targets are related to the development of bulbar-onset ALS. Our research indicates that miR-23a-3p might have an effect on motor neuron loss observed in bulbar-onset ALS and may be a novel target for the therapy of ALS in the future.}, } @article {pmid37290609, year = {2023}, author = {Bai, J and Zhang, X and Wang, H and Yu, W and He, Z and Wang, J and Feng, F and Li, M and Wang, H and Yang, F and Huang, X}, title = {Gender-specific association of uric acid and survival in sporadic amyotrophic lateral sclerosis patients.}, journal = {Brain research}, volume = {1815}, number = {}, pages = {148445}, doi = {10.1016/j.brainres.2023.148445}, pmid = {37290609}, issn = {1872-6240}, mesh = {Humans ; Male ; Female ; *Uric Acid ; *Amyotrophic Lateral Sclerosis ; Creatinine ; }, abstract = {OBJECTIVE: To investigate the relationship between serum uric acid (UA) and survival in sporadic amyotrophic lateral sclerosis (sALS) patients.

METHOD: A total of 801 sporadic amyotrophic lateral sclerosis (sALS) patients fulfilled the revised El Escorial criteria were enrolled and followed up in the study. Baseline clinical data and laboratory variables including gender, age, age of onset, site of onset, disease duration, body mass index (BMI), uric acid (UA), creatinine (Cr), and creatine kinase (CK) were collected during enrollment. Multivariate Cox regression models were used to evaluate the survival-related factors after adjustment for confounders.

RESULTS: The serum UA level was significantly lower in female patients than that in male patients (243.5 vs 314.9 μmol/L, p < 0.001). Gender, BMI, Cr, CK were significantly associated with the level of uric acid according to the linear regression analysis. In the multivariate Cox regression analysis, higher serum UA level (>268.0 μmol/L) was an independent protective factor for prolonged survival among female patients (HR = 0.69, P = 0.042) after adjustment for confounders.

CONCLUSION: The present study provided further support that higher UA was a protective factor for survival in sALS patients, especially in female.}, } @article {pmid37289771, year = {2023}, author = {Ahn, JY and Ryoo, HW and Jung, H and Ro, YS and Park, JH}, title = {Impact of emergency medical service with advanced life support training for adults with out-of-hospital cardiac arrest in the Republic of Korea: A retrospective multicenter study.}, journal = {PloS one}, volume = {18}, number = {6}, pages = {e0286047}, pmid = {37289771}, issn = {1932-6203}, mesh = {Adult ; Humans ; *Cardiopulmonary Resuscitation/methods ; *Emergency Medical Services/methods ; *Out-of-Hospital Cardiac Arrest/therapy ; Pilot Projects ; Registries ; Republic of Korea ; Retrospective Studies ; }, abstract = {Prehospital advanced life support (ALS) has been offered in many countries for patients experiencing out-of-hospital cardiac arrest (OHCA); however, its effectiveness remains unclear. This study aimed to determine the impact of emergency medical service (EMS) with ALS training as a nationwide pilot project for adults with OHCA in the Republic of Korea. This retrospective multicenter observational study was conducted between July 2019 and December 2020 using the Korean Cardiac Arrest Research Consortium registry. The patients were categorized into an intervention group that received EMS with ALS training and a control group that did not receive EMS with ALS training. Conditional logistic regression analysis was performed using matched data to compare clinical outcomes between the two groups. Compared with the control group, the intervention group had a lower rate of supraglottic airway usage (60.5% vs. 75.6%) and a higher rate of undergoing endotracheal intubation (21.7% vs. 6.1%, P < 0.001). In addition, the intervention group was administered more intravenous epinephrine (59.8% vs. 14.2%, P < 0.001) and used mechanical chest compression devices more frequently in prehospital settings than the control group (59.0% vs. 23.8%, P < 0.001). Based on the results of multivariable conditional logistic regression analysis, survival to hospital discharge (odds ratio: 0.48, 95% confidence interval: 0.27-0.87) of the intervention group was significantly lower than that of the control group; however, good neurological outcome was not significantly different between the two groups. In this study, survival to hospital discharge was worse in patients with OHCA who received EMS with ALS training than in those who did not.}, } @article {pmid37289322, year = {2023}, author = {Miscioscia, A and Puthenparampil, M and Blasi, L and Rinaldi, F and Perini, P and Sorarù, G and Gallo, P}, title = {Neurodegeneration in the retina of motoneuron diseases: a longitudinal study in amyotrophic lateral sclerosis and Kennedy's disease.}, journal = {Journal of neurology}, volume = {270}, number = {9}, pages = {4478-4486}, pmid = {37289322}, issn = {1432-1459}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/complications/diagnostic imaging/pathology ; Longitudinal Studies ; *Bulbo-Spinal Atrophy, X-Linked ; Retina/diagnostic imaging/pathology ; *Motor Neuron Disease/pathology ; *Retinal Degeneration/diagnostic imaging/etiology/pathology ; Tomography, Optical Coherence/methods ; Atrophy/pathology ; Motor Neurons/pathology ; }, abstract = {BACKGROUND: To what extent retinal atrophy in neurodegenerative diseases reflects the severity and/or the chronicity of brain pathology or is a local independent phenomenon remains to be clarified. Moreover, whether retinal atrophy has a clinical (diagnostic and prognostic) value in these diseases remains unclear.

OBJECTIVE: To add light on the pathological significance and clinical value of retinal atrophy in patients with amyotrophic lateral sclerosis (ALS) and Kennedy's disease (KD).

METHODS: Thirty-five ALS, thirty-seven KD, and forty-nine age-matched healthy controls (HC) were included in a one-year longitudinal study. Spectrum-domain optical coherence tomography (OCT) was performed at study entry (T0) and after 12 months (T1). Disease duration and functional rating scale (FRS) for ALS and KD patients were correlated to retinal thicknesses.

RESULTS: Compared to HC, peripapillary retinal nerve fiber layer (pRNFL) thickness was significantly thinner in both ALS (p = 0.034) and KD (p = 0.003). pRNFL was thinner in KD compared to ALS, but the difference was not significant. In KD, pRNFL atrophy significantly correlated with both disease severity (r = 0.296, p = 0.035) and disease duration (r = - 0.308, p = 0.013) while no significant correlation was found in ALS (disease severity: r = 0.147, p = 0.238; disease duration: r = - 0.093, p = 0.459). During the follow-up, pRNFL thickness remained stable in KD while significantly decreased in ALS (p = 0.043).

CONCLUSIONS: Our study provides evidence of retinal atrophy in both ALS and KD and suggests that retinal thinning is a primary local phenomenon in motoneuron diseases. The clinical value of pRNFL atrophy in KD is worthy of further investigation.}, } @article {pmid37288776, year = {2023}, author = {Hatch, J and Barkhaus, P and Barnes, B and Beauchamp, M and Benatar, M and Bertorini, T and Bowser, R and Bromberg, M and Brown, A and Mascias Cadavid, J and Carter, GT and Cole, N and Crayle, J and Dimachkie, M and Ennist, D and Feldman, E and Fullam, T and Heiman-Patterson, T and Jhooty, S and Levine, T and Li, X and Lund, I and Mallon, E and Maragakis, N and McDermott, C and Pattee, G and Pierce, K and Ratner, D and Staats, K and Wicks, P and Wiedau, M and Bedlack, R}, title = {ALSUntangled #70: caffeine.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {}, number = {}, pages = {1-5}, doi = {10.1080/21678421.2023.2220742}, pmid = {37288776}, issn = {2167-9223}, abstract = {ALSUntangled reviews alternative and off-label treatments for people living with amyotrophic lateral sclerosis (PALS). Here, we review caffeine which has plausible mechanisms for slowing ALS progression. However, pre-clinical studies are contradictory, and a large case series showed no relationship between caffeine intake and ALS progression rate. While low doses of caffeine are safe and inexpensive, higher doses can cause serious side effects. At this time, we cannot endorse caffeine as a treatment to slow ALS progression.}, } @article {pmid37288312, year = {2023}, author = {Costello, E and Ryan, M and Donohoe, B and Kavanagh, C and Pinto-Grau, M and Doherty, M and McLaughlin, RL and McHutchison, C and Abrahams, S and Heverin, M and Hardiman, O and Pender, N}, title = {Cognitive and neuropsychiatric endophenotypes in amyotrophic lateral sclerosis.}, journal = {Brain communications}, volume = {5}, number = {3}, pages = {fcad166}, pmid = {37288312}, issn = {2632-1297}, abstract = {First- and second-degree relatives of people with amyotrophic lateral sclerosis report higher rates of neuropsychiatric disorders, indicating that risk genes may be pleiotropic, causing multiple phenotypes within kindreds. Such phenotypes may constitute a disease endophenotype that associates with disease liability. We have directly investigated cognitive functioning and neuropsychiatric traits among relatives of people with amyotrophic lateral sclerosis to identify potential endophenotypes of the disease. In a family-based, cross-sectional study design, first- and second-degree relatives of people with amyotrophic lateral sclerosis (n = 149) were compared to controls (n = 60) using an in-depth neuropsychological and neuropsychiatric assessment. Subgroup analyses examined the effect of family history and C9orf72 repeat expansion status (n = 16 positive carriers). Relatives of people with amyotrophic lateral sclerosis had lower scores on executive functioning, language and memory tasks compared to controls, with large effect sizes observed on object naming (d = 0.91, P = 0.00001) and phonemic verbal fluency (d = 0.81, P = 0.0003). Relatives also had higher autism quotient attention to detail traits (d = -0.52, P = 0.005), lower conscientiousness (d = 0.57, P = 0.003) and lower openness to experience personality traits (d = 0.54, P = 0.01) than controls. These effects were typically larger in relatives of people with familial, rather than sporadic, amyotrophic lateral sclerosis and were present in both gene carrier and non-carrier relatives of probands with a C9orf72 repeat expansion. Poorer phonemic fluency and object naming, along with autism and personality traits, are more frequent in relatives of people with amyotrophic lateral sclerosis. Among kindreds carrying the C9orf72 repeat expansion, these traits were identified in relatives regardless of their carrier status, suggesting the presence of a disease-associated endophenotype that is not exclusively mediated by the C9orf72 expansion.}, } @article {pmid37288069, year = {2023}, author = {Corrigan, F and Wee, IC and Collins-Praino, LE}, title = {Chronic motor performance following different traumatic brain injury severity-A systematic review.}, journal = {Frontiers in neurology}, volume = {14}, number = {}, pages = {1180353}, pmid = {37288069}, issn = {1664-2295}, abstract = {INTRODUCTION: Traumatic brain injury (TBI) is now known to be a chronic disease, causing ongoing neurodegeneration and linked to increased risk of neurodegenerative motor diseases, such as Parkinson's disease and amyotrophic lateral sclerosis. While the presentation of motor deficits acutely following traumatic brain injury is well-documented, however, less is known about how these evolve in the long-term post-injury, or how the initial severity of injury affects these outcomes. The purpose of this review, therefore, was to examine objective assessment of chronic motor impairment across the spectrum of TBI in both preclinical and clinical models.

METHODS: PubMed, Embase, Scopus, and PsycINFO databases were searched with a search strategy containing key search terms for TBI and motor function. Original research articles reporting chronic motor outcomes with a clearly defined TBI severity (mild, repeated mild, moderate, moderate-severe, and severe) in an adult population were included.

RESULTS: A total of 97 studies met the inclusion criteria, incorporating 62 preclinical and 35 clinical studies. Motor domains examined included neuroscore, gait, fine-motor, balance, and locomotion for preclinical studies and neuroscore, fine-motor, posture, and gait for clinical studies. There was little consensus among the articles presented, with extensive differences both in assessment methodology of the tests and parameters reported. In general, an effect of severity was seen, with more severe injury leading to persistent motor deficits, although subtle fine motor deficits were also seen clinically following repeated injury. Only six clinical studies investigated motor outcomes beyond 10 years post-injury and two preclinical studies to 18-24 months post-injury, and, as such, the interaction between a previous TBI and aging on motor performance is yet to be comprehensively examined.

CONCLUSION: Further research is required to establish standardized motor assessment procedures to fully characterize chronic motor impairment across the spectrum of TBI with comprehensive outcomes and consistent protocols. Longitudinal studies investigating the same cohort over time are also a key for understanding the interaction between TBI and aging. This is particularly critical, given the risk of neurodegenerative motor disease development following TBI.}, } @article {pmid37287555, year = {2023}, author = {Işık, K and Morkavuk, G and Odabaşı, Z}, title = {Dropped Head Syndrome As a Presenting Sign of Different Diseases: Report of Three Cases.}, journal = {Noro psikiyatri arsivi}, volume = {60}, number = {2}, pages = {185-187}, pmid = {37287555}, issn = {1300-0667}, abstract = {Dropped head is an abnormal forward flexion of the cervical spine. Patients can straighten their heads with support. This condition, which is seen as neck extensor muscle weakness, is defined as 'head ptosis' or 'dropped head syndrome' and is seen in various central and neuromuscular diseases. Myasthenia gravis, inflammatory myopathy, amyotrophic lateral sclerosis, facio-scapulo-humeral dystrophy, nemaline myopathy, carnitine deficiency and spinal muscular atrophy are some of the neuromuscular diseases seen in dropped head cases. We aimed to present 3 different cases with a diagnosis of myasthenia gravis, inflammatory myopathy, and amyotrophic lateral sclerosis presenting with dropped head.}, } @article {pmid37285737, year = {2023}, author = {Taheri, M and Askari, A and Hussen, BM and Eghbali, A and Ghafouri-Fard, S}, title = {A review on the role of MYC-induced long non-coding RNA in human disorders.}, journal = {Pathology, research and practice}, volume = {248}, number = {}, pages = {154568}, doi = {10.1016/j.prp.2023.154568}, pmid = {37285737}, issn = {1618-0631}, mesh = {Humans ; *Carcinoma, Hepatocellular/pathology ; Gene Expression Regulation, Neoplastic ; *Liver Neoplasms/pathology ; *MicroRNAs/genetics/metabolism ; *RNA, Long Noncoding/genetics/metabolism ; }, abstract = {MINCR (MYC-Induced Long Non-Coding RNA) is classified as an lncRNA. It has a significant correlation with MYC gene. MINCR has important roles in the carcinogenesis. It has been approved that this lncRNA can act as molecular sponge for miR-28-5p, miR-708-5p, miR-876-5p and miR-146a-5p. Dysregulated levels of MINCR has been observed in different types of cancer, especially hepatocellular carcinoma. In addition to malignant conditions, schizophrenia and neurodegenerative diseases such as Alzheimer's disease and amyotrophic lateral sclerosis are associated with dysregulation of expression patterns of MINCR. This review outlines MINCR molecular mechanisms of action in different disorders.}, } @article {pmid37284659, year = {2023}, author = {Zhu, Q and Zhou, J and Zhang, Y and Huang, H and Han, J and Cao, B and Xu, D and Zhao, Y and Chen, G}, title = {Risk factors associated with amyotrophic lateral sclerosis based on the observational study: a systematic review and meta-analysis.}, journal = {Frontiers in neuroscience}, volume = {17}, number = {}, pages = {1196722}, pmid = {37284659}, issn = {1662-4548}, abstract = {OBJECTIVE: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder affecting the upper and lower motor neurons. Though the pathogenesis of ALS is still unclear, exploring the associations between risk factors and ALS can provide reliable evidence to find the pathogenesis. This meta-analysis aims to synthesize all related risk factors of ALS to understand this disease comprehensively.

METHODS: We searched the following databases: PubMed, EMBASE, Cochrane library, Web of Science, and Scopus. Moreover, observational studies, including cohort studies, and case-control studies, were included in this meta-analysis.

RESULTS: A total of 36 eligible observational studies were included, and 10 of them were cohort studies and the rest were case-control studies. We found six factors exacerbated the progression of disease: head trauma (OR = 1.26, 95% CI = 1.13, 1.40), physical activity (OR = 1.06, 95% CI = 1.04, 1.09), electric shock (OR = 2.72, 95% CI = 1.62, 4.56), military service (OR = 1.34, 95% CI = 1.11, 1.61), pesticides (OR = 1.96, 95% CI = 1.7, 2.26), and lead exposure (OR = 2.31, 95% CI = 1.44, 3.71). Of note, type 2 diabetes mellitus was a protective factor for ALS. However, cerebrovascular disease (OR = 0.99, 95% CI = 0.75, 1.29), agriculture (OR = 1.22, 95% CI = 0.74, 1.99), industry (OR = 1.24, 95% CI = 0.81, 1.91), service (OR = 0.47, 95% CI = 0.19, 1.17), smoking (OR = 1.25, 95% CI = 0.5, 3.09), chemicals (OR = 2.45, 95% CI = 0.89, 6.77), and heavy metal (OR = 1.5, 95% CI = 0.47, 4.84) were not risk factors for ALS based on meta-analyses.

CONCLUSIONS: Head trauma, physical activity, electric shock, military service, pesticides, and lead were risk factors for ALS onset and progression. But DM was a protective factor. This finding provides a better understanding of ALS risk factors with strong evidence for clinicians to rationalize clinical intervention strategies.

INPLSY REGISTRATION NUMBER: https://inplasy.com/inplasy-2022-9-0118/, INPLASY202290118.}, } @article {pmid37284147, year = {2022}, author = {}, title = {66th Annual Meeting of the German Society of Neuropathology and Neuroanatomy (DGNN) - Meeting Abstracts: Berlin, November 1-5, 2022.}, journal = {Free neuropathology}, volume = {3}, number = {}, pages = {20}, doi = {10.17879/freeneuropathology-2022-4366}, pmid = {37284147}, issn = {2699-4445}, abstract = {Liebe Kolleginnen und Kollegen, zur 66. Jahrestagung der Deutschen Gesellschaft für Neuropathologie und Neuroanatomie im Rahmen der Neurowoche vom 1. bis zum 5. November 2022 begrüße ich Sie herzlich in Berlin. Die letzten Jahre haben eine enorme Erweiterung der analytischen Methodik mit Schwerpunkt auf molekularen Untersuchungen gebracht. Ein großer Teil dieser Untersuchungen wurde in unseren Einrichtungen entwickelt und wird dort erbracht. In der Tat hat sich die Neuropathologie zu einem Motor der neuroonkologischen und neurowissenschaftlichen Forschung entwickelt und deutschsprachige neuropathologische Institutionen haben wesentlich dazu beigetragen. Ganz neue Therapien bauen auf diese Erkenntnisse auf. Dadurch sind wir für die Versorgung unserer Patienten wichtiger denn jeher. Deswegen sehe ich einen großen und zunehmenden Bedarf dem wir Neuropathologen nachkommen müssen. Alle Schwerpunkte unseres Faches sind hiervon betroffen, die Gehirntumordiagnostik, die neurodegenerativen Erkrankungen, Entzündung und Erkrankungen der Muskeln und der Nerven. Wir arbeiten eng mit unseren Kollegen aus der Neuroonkologie, Neuropädiatrie, Neurologie Neurochirurgie und Neuroradiologie zusammen. Der interdisziplinäre Austausch hat einen hohen Stellenwert und wir freuen uns deshalb besonders, dass unsere Jahrestagung in diesem Jahr wieder im Rahmen der Neurowoche stattfindet, was die Kommunikation und den Wissenstransfer über die Fächergrenzen beflügelt. Dieses Jahr wollen wir besonders die jungen Neuropathologen und Neuropathologinnen in den Vordergrund stellen. Sie sollen unser Fach als lebendig und besonders zukunftsfähig erleben. Von ihnen erwarten wir die Dynamik, den Einsatz und den Ideenreichtum, der die Neuropathologie in den nächsten Jahren noch weiter zu einer zentralen Querschnittsplattform für die Neurofächer machen wird. Wir haben einen Kongressstrang mit wissenschaftlichen Sitzungen am Donnerstag, Freitag und Samstag ausgerichtet. Sie dürfen Vorträge mit jungen neuropathologischen Expertinnen und Experten sowie von jungen Nachwuchswissenschaftlerinnen und Nachwuchswissenschaftlern erwarten. Ich freue mich auf lebhafte Diskussionen und spannende interdisziplinäre Debatten! Ihr Prof. Dr. Andreas von Deimling Universitätsklinikum Heidelberg Neuropathologie.}, } @article {pmid37282469, year = {2023}, author = {Dash, BP and Hermann, A}, title = {Combination of novel RNA sequencing and sophisticated network modeling to reveal a common denominator in amyotrophic lateral sclerosis?.}, journal = {Neural regeneration research}, volume = {18}, number = {11}, pages = {2403-2405}, pmid = {37282469}, issn = {1673-5374}, } @article {pmid37280513, year = {2023}, author = {Vidovic, M and Freigang, M and Aust, E and Linse, K and Petzold, D and Günther, R}, title = {Cognitive performance of adult patients with SMA before and after treatment initiation with nusinersen.}, journal = {BMC neurology}, volume = {23}, number = {1}, pages = {216}, pmid = {37280513}, issn = {1471-2377}, mesh = {Humans ; Adult ; Longitudinal Studies ; *Muscular Atrophy, Spinal/drug therapy ; *Spinal Muscular Atrophies of Childhood ; Cognition ; }, abstract = {BACKGROUND: Spinal muscular atrophy (SMA) is a genetic neuromuscular disease caused by mutations of the SMN1 gene. Deficient SMN protein causes irreversible degeneration of alpha motor neurons characterized by progressive muscle weakness and atrophy. Considering that SMA is a multi-systemic disorder and SMN protein was found to be expressed in cortical structures, the cognitive profile of adult patients with SMA has recently been of particular interest. With nusinersen, a novel, disease-modifying drug has been established, but its effects on neuropsychological functions have not been validated yet. Aim of this study was to investigate the cognitive profile of adult patients with SMA during treatment initiation with nusinersen and to reveal improvement or deterioration in cognitive performance.

METHODS: This monocentric longitudinal study included 23 patients with SMA type 2 and 3. All patients were assessed with the Edinburgh Cognitive and Behavioral ALS Screen (ECAS) before and after 14 months of treatment initiation with nusinersen. Additionally, motor function was evaluated by Hammersmith Functional Motor Scale Expanded (HFMSE), Revised Upper Limb Module (RULM) and Amyotrophic Lateral Sclerosis Functional Rating Scale Revised (ALSFRS-R).

RESULTS: Of the treatment-naive patients, only three were below the age- and education-matched cut-off for cognitive impairment in the ECAS total score. Significant differences between SMA type 2 and 3 were only detected in the domain of Language. After 14 months of treatment, patients showed significant improvement of absolute scores in all three ALS-specific domains, in the non-ALS-specific domain of Memory, in both subscores and in the ECAS total score. No associations were detected between cognitive and functional outcome measures.

CONCLUSIONS: In some adult patients with SMA abnormal cognitive performance in ALS-specific functions of the ECAS was evident. However, the presented results suggest no clinically significant cognitive changes during the observed treatment period with nusinersen.}, } @article {pmid37280477, year = {2023}, author = {Nakamagoe, K and Matsumoto, S and Touno, N and Tateno, I and Koganezawa, T}, title = {Correction to: Saccadic oscillations as a biomarker of clinical symptoms in amyotrophic lateral sclerosis.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {44}, number = {10}, pages = {3767}, doi = {10.1007/s10072-023-06889-4}, pmid = {37280477}, issn = {1590-3478}, } @article {pmid37280445, year = {2023}, author = {Ohgaki, Y and Ishibashi, Y and Hatao, F and Furuta, R and Saito, N and Inayoshi, R and Morita, Y}, title = {Laparoscopically assisted percutaneous endoscopic gastrostomy performed for remnant stomach in patient with amyotrophic lateral sclerosis: a case report.}, journal = {Surgical case reports}, volume = {9}, number = {1}, pages = {98}, pmid = {37280445}, issn = {2198-7793}, abstract = {BACKGROUND: Although percutaneous endoscopic gastrostomy (PEG) offers better access to the gastrointestinal system, in patients with previous abdominal surgery, PEG can be unsuccessful. Laparoscopically assisted percutaneous endoscopic gastrostomy (LAPEG) is indicated for such patients. However, patients with amyotrophic lateral sclerosis (ALS) may be more susceptible to anesthesia-related complications than other patients, requiring the indications for LAPEG, along with perioperative management, to be considered carefully.

CASE PRESENTATION: A 70-year-old, male patient with ALS was referred to our hospital for a gastrostomy for progressive dysphagia. He had undergone an open distal gastrectomy for gastric ulcer perforation in his twenties. Upper gastrointestinal endoscopy denied the transillumination sign and focal finger invagination. Because the risk of respiratory complications caused by general anesthesia was not considered serious, the decision was made to perform a LAPEG. Under careful, intraoperative airway management and neuromuscular monitoring, adhesiolysis was performed to increase mobility of the remnant stomach. A gastrostomy tube was inserted through the abdominal wall and into the remnant stomach under laparoscopic and endoscopic guidance. The patient was discharged in stable condition on postoperative day 3 without any respiratory complications.

CONCLUSIONS: LAPEG was able to be performed in a patient with ALS with a previous gastrectomy. A perioperative team comprised of neurologists, endoscopists, surgeons, anesthesiologists, and nurses who are fully conversant with ALS must be assembled to deal with potentially complex medical issues related to the procedure and anesthetic and perioperative management.}, } @article {pmid37280161, year = {2023}, author = {Nakamura, M and Nishii, M and Kume, K and Kawakami, H and Yakushiji, Y}, title = {An autopsy case of sporadic, adult-onset amyotrophic lateral sclerosis with heterozygous p.N1935S SETX gene variant.}, journal = {Journal of neuropathology and experimental neurology}, volume = {82}, number = {8}, pages = {734-738}, doi = {10.1093/jnen/nlad041}, pmid = {37280161}, issn = {1554-6578}, mesh = {Adult ; Humans ; *Amyotrophic Lateral Sclerosis/genetics ; Autopsy ; DNA Helicases/genetics ; Heterozygote ; Multifunctional Enzymes/genetics ; Mutation/genetics ; RNA Helicases/genetics ; }, } @article {pmid37279716, year = {2023}, author = {Clair, S and Kirk, R and Coulter, ID and Saller, R}, title = {A Pragmatic Historical Assessment Tool: A New Systematic Framework for the Collation and Evaluation of Documented Empirical Effectiveness and Safety of Traditional Plant Medicines in the European Materia Medica.}, journal = {Complementary medicine research}, volume = {30}, number = {4}, pages = {340-353}, doi = {10.1159/000531021}, pmid = {37279716}, issn = {2504-2106}, mesh = {Humans ; *Materia Medica ; Medicine, Traditional/methods ; Phytotherapy ; Plant Extracts ; Plant Oils ; *Plants, Medicinal ; }, abstract = {INTRODUCTION: Traditional plant medicines (TPMs) are plant-derived therapeutic products prepared and applied according to longstanding medical customs. Around the world they are widely used in primary and preventative health care. The World Health Organization (WHO) calls in its Traditional Medicine Strategy 2014-2023 for Member States to provide a regulatory framework so that the formal contribution of traditional therapeutics can be advanced in national systems of health care. Evidence of effectiveness and safety is paramount for the regulatory integration of TPMs; however, a presumed lack of such "evidence" is one obstacle for full integration. The consequential health policy question is how to systematically evaluate therapeutic claims relating to herbal remedies when the extant evidence is predominantly based on historical and contemporary clinical usage, i.e., is empiricist in nature. This paper introduces a new method along with several illustrative examples.

METHOD: Our research design employs a longitudinal, comparative textual analysis of standard textbooks of the professional European medical literature from the early modern period (1588/1664) onwards to today. It then triangulated these intergenerationally documented clinical observations on two exemplars (Arnica and St. John's Wort) with corresponding listings in multiple qualitative and quantitative sources. A Pragmatic Historical Assessment (PHA) tool was developed and tested as a method to systematically collate the large amount of pharmacological data recorded in these judiciously selected sources. The evidential validity of longstanding professional clinical knowledge could thus be compared with therapeutic indications approved in official and authoritative sources (pharmacopoeias, monographs) and with those supported by contemporary scientific research (randomised-controlled trials [RCTs], experimental research).

RESULTS: There was high congruency between therapeutic indications that are based on repeated empirical observations from professional patient care (empirical evidence), those approved in pharmacopoeias and monographs, and modern scientific evidence based on RCTs. The extensive herbal triangulation confirmed parallel records of all main therapeutic indications of the exemplars across all qualitative and quantitative sources over the past 400 years.

CONCLUSIONS: Historical clinical medical textbooks and contemporary phytotherapeutic equivalents are the key repository of repeatedly evaluated therapeutic plant knowledge. The professional clinical literature proved to be a reliable and verifiable body of empirical evidence that harmonised with contemporary scientific assessments. The newly developed PHA tool provides a coding framework for the systematic collation and evaluation of empirical data on the effectiveness and safety of TPMs. It is suggested as a feasible and efficient tool to extend evidence typologies that substantiate therapeutic claims for TPMs as part of an evidence-based regulatory framework that formally integrates these medically and culturally important therapeutics.

UNLABELLED: EinleitungTraditionelle pflanzliche Arzneimittel sind aus Pflanzen gewonnene Heilmittel, die gemäß langjähriger medizinischer Praxis zubereitet und angewendet werden. Weltweit sind sie in der primären und präventiven Gesundheitsversorgung weit verbreitet. Die Weltgesundheitsorganisation (WHO) ruft in ihrer Traditional Medicine Strategy 2014–2023 die Mitgliedstaaten dazu auf, regulatorische Rahmenbedingungen zu schaffen, welche den formellen Beitrag traditioneller Therapeutika in den nationalen Gesundheitssystemen fördern. Der Nachweis von Wirksamkeit und Sicherheit ist von zentraler Bedeutung für die regulatorische Integration traditioneller pflanzlicher Arzneimittel, doch das angebliche Fehlen solcher “Nachweise“ ist eine der Hürden für die vollständige Integration. Daraus ergibt sich die gesundheitspolitische Frage, wie man therapeutische Anwendungsgebiete pflanzlicher Heilmittel systematisch evaluieren kann, wenn die vorliegende Evidenz überwiegend auf deren historischer und aktueller klinischen Verwendung beruht, also empirischer Natur ist. In dieser Arbeit wird eine neue Methode mitsamt veranschaulichenden Beispielen vorgestellt.MethodenUnser Forschungsansatz beruhte auf einer longitudinalen, vergleichenden Textanalyse von Standard-Lehrwerken der europäischen medizinischen Fachliteratur ausgehend von der frühen Neuzeit (1588/1664) bis heute. Die über Generationen dokumentierten klinischen Beobachtungen wurden anhand von zwei Beispielen (Arnika and Johanniskraut) mit den diesbezüglichen Angaben in unterschiedlichen qualitativen und quantitativen Quellen trianguliert. Ein Pragmatisch‐Historisches Auswertungstool (PHA) wurde als Methode entwickelt und getestet, um die großen Mengen der in diesen kritisch ausgewählten Quellen enthaltenen pharmakologischen Daten systematisch zu erfassen. Die Evidenzvalidität des langjährigen klinischen Fachwissens konnte so mit den therapeutischen Anwendungsgebieten verglichen werden, die in offiziellen und autoritativen Quellen (Pharmakopöen, Monografien) zugelassen sind, sowie mit denjenigen, die durch zeitgenössische wissenschaftliche Forschung gestützt werden (randomisierte kontrollierte Studien [RCTs], experimentelle Forschung).ErgebnisseEs bestand ein hohes Maß an Kongruenz zwischen den therapeutischen Anwendungsgebieten, welche auf wiederholte empirische Beobachtung aus der professionellen Patientenversorgung beruhen (empirische Evidenz), den zugelassenen Indikationen in Pharmakopöen und Monographien sowie der aktuellen wissenschaftlichen Evidenz basierend auf klinischen Studien. Die umfassende pflanzenbezogene Triangulation bestätigte parallele Aufzeichnungen aller wesentlichen Anwendungsgebiete der untersuchten Beispiele in allen qualitativen und quantitativen Quellen über die letzten 400 Jahre hinweg.SchlussfolgerungenHistorische Lehrbücher für klinische Medizin und zeitgenössische phytotherapeutische Äquivalente sind die wichtigsten Quellen von wiederholt evaluiertem therapeutischem Wissen zu Heilpflanzen. Die klinische Fachliteratur erwies sich als zuverlässiger und verifizierbarer Korpus empirischer Evidenz, der mit aktuellen wissenschaftlichen Untersuchungen übereinstimmte. Das neu entwickelte PHA-Verfahren bietet ein Kodierungs‐Instrument für das systematische Erfassen und Auswerten empirischer Daten zur Wirksamkeit und Sicherheit von traditionellen pflanzlichen Arzneimitteln. Das PHA‐Verfahren wird als praktikables und effizientes Instrument zur Erweiterung der Evidenz‐Typologien empfohlen, indem es therapeutische Indikationen für traditionelle pflanzliche Arzneimittel untermauern kann, so dass diese medizinisch und kulturell wichtigen Therapeutika in einen evidenz-basierten regulatorischen Rahmen integriert werden können.}, } @article {pmid37279497, year = {2023}, author = {van Selms, MKA and Henselijn, JCR and Schaminée, ACM and van der Meijden, C and van der Linden, MW}, title = {[Oral care in patients with ALS: an exploratory study].}, journal = {Nederlands tijdschrift voor tandheelkunde}, volume = {130}, number = {6}, pages = {287-294}, doi = {10.5177/ntvt.2023.06.23013}, pmid = {37279497}, issn = {0028-2200}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis ; Toothbrushing ; Emotions ; Gagging ; }, abstract = {For this exploratory study, ALS patients and their partners/caregivers were interviewed to find out what problems they encounter when performing oral care. In addition, the tooth brushing procedure was recorded on video. Most mentioned by the six patients was that the performance of oral care is hampered by the loss of motor skills and by the gag reflex. They also mentioned various adjustments that would ease dental visits. Three of the four partners indicated that an instructional video would have additional value, and two partners said they sometimes felt insecure whether they were performing oral care properly. The five videos showed that there are major differences regarding tooth brushing duration, which surfaces are being brushed, and the brushing technique. This study shows that there are several ways in which oral care is performed in ALS patients. Furthermore, not all caregivers are aware of how oral care should be performed.}, } @article {pmid37279301, year = {2023}, author = {Fehlings, MG and Moghaddamjou, A and Harrop, JS and Stanford, R and Ball, J and Aarabi, B and Freeman, BJC and Arnold, PM and Guest, JD and Kurpad, SN and Schuster, JM and Nassr, A and Schmitt, KM and Wilson, JR and Brodke, DS and Ahmad, FU and Yee, A and Ray, WZ and Brooks, NP and Wilson, J and Chow, DS and Toups, EG and Kopjar, B}, title = {Safety and Efficacy of Riluzole in Acute Spinal Cord Injury Study (RISCIS): A Multi-Center, Randomized, Placebo-Controlled, Double-Blinded Trial.}, journal = {Journal of neurotrauma}, volume = {40}, number = {17-18}, pages = {1878-1888}, pmid = {37279301}, issn = {1557-9042}, mesh = {Humans ; Riluzole/adverse effects ; *Neuroprotective Agents/adverse effects ; Pandemics ; Prospective Studies ; Treatment Outcome ; Double-Blind Method ; *COVID-19 ; *Spinal Cord Injuries/drug therapy/chemically induced ; }, abstract = {Riluzole is a sodium-glutamate antagonist that attenuates neurodegeneration in amyotrophic lateral sclerosis (ALS). It has shown favorable results in promoting recovery in pre-clinical models of traumatic spinal cord injury (tSCI) and in early phase clinical trials. This study aimed to evaluate the efficacy and safety of riluzole in acute cervical tSCI. An international, multi-center, prospective, randomized, double-blinded, placebo-controlled, adaptive, Phase III trial (NCT01597518) was undertaken. Patients with American Spinal Injury Association Impairment Scale (AIS) A-C, cervical (C4-C8) tSCI, and <12 h from injury were randomized to receive either riluzole, at an oral dose of 100 mg twice per day (BID) for the first 24 h followed by 50 mg BID for the following 13 days, or placebo. The primary efficacy end-point was change in Upper Extremity Motor (UEM) scores at 180 days. The primary efficacy analyses were conducted on an intention to treat (ITT) and completed cases (CC) basis. The study was powered at a planned enrolment of 351 patients. The trial began in October 2013 and was halted by the sponsor on May 2020 (and terminated in April 2021) in the face of the global COVID-19 pandemic. One hundred ninety-three patients (54.9% of the pre-planned enrolment) were randomized with a follow-up rate of 82.7% at 180 days. At 180 days, in the CC population the riluzole-treated patients compared with placebo had a mean gain of 1.76 UEM scores (95% confidence interval: -2.54-6.06) and 2.86 total motor scores (CI: -6.79-12.52). No drug-related serious adverse events were associated with the use of riluzole. Additional pre-planned sensitivity analyses revealed that in the AIS C population, riluzole was associated with significant improvement in total motor scores (estimate: standard error [SE] 8.0; CI 1.5-14.4) and upper extremity motor scores (SE 13.8; CI 3.1-24.5) at 6 months. AIS B patients had higher reported independence, measured by the Spinal Cord Independence Measure score (45.3 vs. 27.3; d: 18.0 CI: -1.7-38.0) and change in mental health scores, measured by the Short Form 36 mental health domain (2.01 vs. -11.58; d: 13.2 CI: 1.2-24.8) at 180 days. AIS A patients who received riluzole had a higher average gain in neurological levels at 6 months compared with placebo (mean 0.50 levels gained vs. 0.12 in placebo; d: 0.38, CI: -0.2-0.9). The primary analysis did not achieve the predetermined end-point of efficacy for riluzole, likely related to insufficient power. However, on pre-planned secondary analyses, all subgroups of cervical SCI subjects (AIS grades A, B and C) treated with riluzole showed significant gains in functional recovery. The results of this trial may warrant further investigation to extend these findings. Moreover, guideline development groups may wish to assess the possible clinical relevance of the secondary outcome analyses, in light of the fact that SCI is an uncommon orphan disorder without an accepted neuroprotective treatment.}, } @article {pmid37279290, year = {2023}, author = {Schwartzenburg, JB and Cruise, SC and Reed, RE and Hutchinson, CM and Mirzalieva, OS and Edwards, KN and Edwards, S and Gilpin, NW and Molina, PE and Desai, SD}, title = {Neuropathological Outcomes of Traumatic Brain Injury and Alcohol Use in Males and Females: Studies Using Pre-Clinical Rodent and Clinical Human Specimens.}, journal = {Journal of neurotrauma}, volume = {40}, number = {21-22}, pages = {2410-2426}, pmid = {37279290}, issn = {1557-9042}, support = {R01 AA025792/AA/NIAAA NIH HHS/United States ; T32 AA007577/AA/NIAAA NIH HHS/United States ; R21 NS060960/NS/NINDS NIH HHS/United States ; }, mesh = {Humans ; Male ; Female ; Animals ; Rats ; *Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology ; Rodentia/metabolism ; *Brain Injuries, Traumatic/metabolism ; DNA-Binding Proteins/genetics ; *Chronic Traumatic Encephalopathy ; Alcohol Drinking ; }, abstract = {Traumatic brain injury (TBI) and alcohol misuse are inextricably linked and can increase the risk for development of neurodegenerative diseases, particularly in military veterans and contact sport athletes. Proteinopathy (defects in protein degradation) is considered an underlying factor in neurodegenerative diseases. Whether it contributes to TBI/alcohol-mediated neurodegeneration is unexplored, however. Our recent studies have identified ISGylation, a conjugated form of ISG15 (Interferon-Stimulated Gene 15) and inducer of proteinopathy, as a potential mechanistic link underlying TBI-mediated neurodegeneration and proteinopathy in veterans. In the current study, a rat model of combined TBI and alcohol use was utilized to investigate the same relationship. Here, we report sustained induction of Interferon β (IFNβ), changes in TAR DNA Binding 43 (TDP-43) ISGylation levels, TDP-43 proteinopathy (C-terminal fragmentation [CTF]), and neurodegeneration in the ventral horns of the lumbar spinal cords (LSCs) and/or motor cortices (MCs) of female rats post-TBI in a time-dependent manner. In males, these findings mostly remained non-significant, although moderate alcohol use appears to decrease neurodegeneration in males (but not females) post-TBI. We, however, do not claim that moderate alcohol consumption is beneficial for preventing TBI-mediated neurodegeneration. We have previously demonstrated that ISGylation is increased in the LSCs of veterans with TBI/ALS (amyotrophic lateral sclerosis). Here, we show increased ISGylation of TDP-43 in the LSCs of TBI/ALS-afflicted female veterans compared with male veterans. Knowing that ISGylation induces proteinopathy, we suggest targeting ISGylation may prevent proteinopathy-mediated neurodegeneration post-TBI, particularly in women; however, causal studies are required to confirm this claim.}, } @article {pmid37279166, year = {2023}, author = {Anand, T and Ishaque, A and Ta, D and Khan, MU and Bharti, K and Wu, A and Krebs, D and Beaulieu, C and Seres, P and Kalra, S}, title = {Characterization of white matter alterations using diffusion kurtosis imaging in patients with amyotrophic lateral sclerosis.}, journal = {Brain and behavior}, volume = {13}, number = {7}, pages = {e3102}, pmid = {37279166}, issn = {2162-3279}, support = {//CIHR/Canada ; }, mesh = {Humans ; Diffusion Tensor Imaging/methods ; *White Matter/diagnostic imaging/pathology ; *Amyotrophic Lateral Sclerosis/diagnostic imaging ; Brain/diagnostic imaging/pathology ; *Brain Diseases/pathology ; }, abstract = {BACKGROUND: To evaluate the degeneration of the corticospinal tract (CST) and corpus callosum (CC) in patients with motor neuron disease and upper motor neuron (UMN) dysfunction using diffusion kurtosis imaging (DKI).

METHODS: Twenty-seven patients and 33 healthy controls underwent magnetic resonance imaging along with clinical and neuropsychological testing. Tractography of diffusion tensor images was performed to extract tracts of the bilateral CST and CC. Group mean differences both across the entire averaged tract and along each tract were assessed, including correlations between diffusion metrics and clinical measures. Tract-based spatial statistics (TBSS) was performed to evaluate the spatial distribution of whole-brain microstructural abnormalities in patients.

RESULTS: In comparison to controls, patients had significantly higher mean and radial diffusivity and lower fractional anisotropy (FA), kurtosis anisotropy, mean kurtosis (MK), and radial kurtosis (RK) in the CST and CC (p < .017). Along-the-tract analysis revealed changes concentrated in the posterior limb of the internal capsule, corona radiata, and primary motor cortex (false-discovery rate p < .05). FA of the left CST correlated with disease progression rate, whereas MK of the bilateral CST correlated with UMN burden (p < .01). TBSS results corroborated along-tract analysis findings and additionally revealed reduced RK and MK in the fornix, where diffusion tensor imaging (DTI) changes were absent.

CONCLUSION: DKI abnormalities in the CST and CC are present in patients with UMN dysfunction, potentially revealing complementary information to DTI regarding the pathology and microstructural alterations occurring in such patients. DKI shows promise as a potential in vivo biomarker for cerebral degeneration in amyotrophic lateral sclerosis.}, } @article {pmid37277972, year = {2023}, author = {Mori, K and Gotoh, S and Ikeda, M}, title = {Aspects of degradation and translation of the expanded C9orf72 hexanucleotide repeat RNA.}, journal = {Journal of neurochemistry}, volume = {166}, number = {2}, pages = {156-171}, doi = {10.1111/jnc.15847}, pmid = {37277972}, issn = {1471-4159}, mesh = {Humans ; C9orf72 Protein/genetics ; Proteins/genetics/metabolism ; RNA/genetics/metabolism ; *Frontotemporal Dementia/genetics ; *Amyotrophic Lateral Sclerosis/genetics ; DNA Repeat Expansion/genetics ; }, abstract = {An hexanucleotide repeat expansion mutation in the non-coding region of C9orf72 gene causes frontotemporal dementia and amyotrophic lateral sclerosis. This mutation is estimated to be the most frequent genetic cause of these currently incurable diseases. Since the mutation causes autosomal dominantly inherited diseases, disease cascade essentially starts from the expanded DNA repeats. However, molecular disease mechanism is inevitably complex because possible toxic entity for the disease is not just functional loss of translated C9ORF72 protein, if any, but potentially includes bidirectionally transcribed expanded repeat containing RNA and their unconventional repeat-associated non-AUG translation products in all possible reading frames. Although the field learned so much about the disease since the identification of the mutation in 2011, how the expanded repeat causes a particular type of fronto-temporal lobe dominant neurodegeneration and/or motor neuron degeneration is not yet clear. In this review, we summarize and discuss the current understandings of molecular mechanism of this repeat expansion mutation with focuses on the degradation and translation of the repeat containing RNA transcripts.}, } @article {pmid37276151, year = {2024}, author = {Peters, GA and Cash, RE and Goldberg, SA and Kolb, LM and Ordoobadi, AJ and Camargo, CA}, title = {Emergency Medical Services Management of Bronchospasm in the United States: A Cross-Sectional Analysis and Nationwide Quality Assessment.}, journal = {Prehospital emergency care}, volume = {28}, number = {2}, pages = {231-242}, doi = {10.1080/10903127.2023.2220021}, pmid = {37276151}, issn = {1545-0066}, mesh = {Adult ; Aged ; Child ; Female ; Humans ; Male ; Adrenal Cortex Hormones ; *Bronchial Spasm/drug therapy ; Cross-Sectional Studies ; *Emergency Medical Services ; Oxygen ; United States ; Child, Preschool ; Adolescent ; Middle Aged ; }, abstract = {Background/Objective: Bronchospasm, caused by asthma and other related conditions, is a significant cause of morbidity and mortality commonly managed by emergency medical services (EMS). We aimed to evaluate the quality of prehospital management of bronchospasm by EMS in the US.Methods: The National EMS Information System Public Release Research dataset, a nationwide convenience sample of prehospital patient care report data from 2018 to 2019, was used to capture 9-1-1 activations where patients aged ≥2 years were treated and transported by EMS for suspected bronchospasm. First, we described the extent to which EMS care met eight quality measures identified from available statewide EMS protocols, existing quality measures, and national guidelines. Second, we quantified the extent of risk-standardized agency-level variation in administration of inhaled beta agonists and systemic corticosteroids using logistic regression models, accounting for patient characteristics, severity, and clustering by agencies. Third, we compared rates of completed prehospital interventions between pediatric (age <18 years) versus adult patients using two-sample t-tests.Results: A total of 1,336,988 EMS encounters for suspected bronchospasm met inclusion criteria. Median age of patients was 66 years, with only 4% pediatric; 55% were female. Advanced life support (ALS) units managed 94% of suspected bronchospasm. Respiratory rate (98%) and pulse oximetry (96%) were documented in nearly all cases. Supplemental oxygen was administered to hypoxic patients by 65% of basic life support (BLS) and 73% of ALS units. BLS administered inhaled beta-agonist therapy less than half the time (48%), compared to 77% by ALS. ALS administered inhaled anticholinergic therapy in 38% of cases, and systemic corticosteroids in 19% of cases. Pediatric patients were significantly less likely to receive supplemental oxygen when hypoxic, inhaled beta-agonists, inhaled anticholinergics, or systemic corticosteroids.Conclusions: We found important gaps in recent EMS practice for prehospital care of suspected bronchospasm. We highlight three targets for improvement: inhaled beta-agonist administration by BLS, systemic corticosteroid administration by ALS, and increased interventions for pediatric patients. These findings indicate important areas for research, protocol modification, and quality improvement efforts to improve EMS management of bronchospasm.}, } @article {pmid37274187, year = {2023}, author = {Santarelli, S and Londero, C and Soldano, A and Candelaresi, C and Todeschini, L and Vernizzi, L and Bellosta, P}, title = {Drosophila melanogaster as a model to study autophagy in neurodegenerative diseases induced by proteinopathies.}, journal = {Frontiers in neuroscience}, volume = {17}, number = {}, pages = {1082047}, pmid = {37274187}, issn = {1662-4548}, abstract = {Proteinopathies are a large group of neurodegenerative diseases caused by both genetic and sporadic mutations in particular genes which can lead to alterations of the protein structure and to the formation of aggregates, especially toxic for neurons. Autophagy is a key mechanism for clearing those aggregates and its function has been strongly associated with the ubiquitin-proteasome system (UPS), hence mutations in both pathways have been associated with the onset of neurodegenerative diseases, particularly those induced by protein misfolding and accumulation of aggregates. Many crucial discoveries regarding the molecular and cellular events underlying the role of autophagy in these diseases have come from studies using Drosophila models. Indeed, despite the physiological and morphological differences between the fly and the human brain, most of the biochemical and molecular aspects regulating protein homeostasis, including autophagy, are conserved between the two species.In this review, we will provide an overview of the most common neurodegenerative proteinopathies, which include PolyQ diseases (Huntington's disease, Spinocerebellar ataxia 1, 2, and 3), Amyotrophic Lateral Sclerosis (C9orf72, SOD1, TDP-43, FUS), Alzheimer's disease (APP, Tau) Parkinson's disease (a-syn, parkin and PINK1, LRRK2) and prion diseases, highlighting the studies using Drosophila that have contributed to understanding the conserved mechanisms and elucidating the role of autophagy in these diseases.}, } @article {pmid37274121, year = {2023}, author = {Keukeleire, P and Makrodimitris, S and Reinders, M}, title = {Cell type deconvolution of methylated cell-free DNA at the resolution of individual reads.}, journal = {NAR genomics and bioinformatics}, volume = {5}, number = {2}, pages = {lqad048}, pmid = {37274121}, issn = {2631-9268}, abstract = {Cell-free DNA (cfDNA) are DNA fragments originating from dying cells that are detectable in bodily fluids, such as the plasma. Accelerated cell death, for example caused by disease, induces an elevated concentration of cfDNA. As a result, determining the cell type origins of cfDNA molecules can provide information about an individual's health. In this work, we aim to increase the sensitivity of methylation-based cell type deconvolution by adapting an existing method, CelFiE, which uses the methylation beta values of individual CpG sites to estimate cell type proportions. Our new method, CelFEER, instead differentiates cell types by the average methylation values within individual reads. We additionally improved the originally reported performance of CelFiE by using a new approach for finding marker regions that are differentially methylated between cell types. We show that CelFEER estimates cell type proportions with a higher correlation (r = 0.94 ± 0.04) than CelFiE (r = 0.86 ± 0.09) on simulated mixtures of cell types. Moreover, we show that the cell type proportion estimated by CelFEER can differentiate between ALS patients and healthy controls, between pregnant women in their first and third trimester, and between pregnant women with and without gestational diabetes.}, } @article {pmid37273905, year = {2023}, author = {McIntosh, J and Mekrouda, I and Dashti, M and Giuraniuc, CV and Banks, RW and Miles, GB and Bewick, GS}, title = {Development of abnormalities at the neuromuscular junction in the SOD1-G93A mouse model of ALS: dysfunction then disruption of postsynaptic structure precede overt motor symptoms.}, journal = {Frontiers in molecular neuroscience}, volume = {16}, number = {}, pages = {1169075}, pmid = {37273905}, issn = {1662-5099}, abstract = {INTRODUCTION: The ultimate deficit in amyotrophic lateral sclerosis (ALS) is neuromuscular junction (NMJ) loss, producing permanent paralysis, ultimately in respiratory muscles. However, understanding the functional and structural deficits at NMJs prior to this loss is crucial for therapeutic strategy design. Should early interventions focus on reversing denervation, or supporting largely intact NMJs that are functionally impaired? We therefore determined when functional and structural deficits appeared in diaphragmatic NMJs relative to the onset of hindlimb tremor (the first overt motor symptoms) in vivo in the SOD1-G93A mouse model of ALS.

MATERIALS AND METHODS: We employed electrophysiological recording of NMJ postsynaptic potentials for spontaneous and nerve stimulation-evoked responses. This was correlated with fluorescent imaging microscopy of the postsynaptic acetylcholine receptor (AChR) distribution throughout the postnatal developmental timecourse from 2 weeks to early symptomatic ages.

RESULTS: Significant reduction in the amplitudes of spontaneous miniature endplate potentials (mEPPs) and evoked EPPs emerged only at early symptomatic ages (in our colony, 18-22 weeks). Reductions in mEPP frequency, number of vesicles per EPP, and EPP rise time were seen earlier, at 16weeks, but this reversed by early symptomatic ages. However, the earliest and most striking impairment was an inability to maintain EPP amplitude during a 20 Hz stimulus train, which appeared 6 weeks before overt in vivo motor symptoms. Despite this, fluorescent α-bungarotoxin labelling revealed no systematic, progressive changes in 11 comprehensive NMJ morphological parameters (area, shape, compactness, number of acetylcholine receptor, AChR, regions, etc.) with disease progression. Rather, while NMJs were largely normally-shaped, from 16 weeks there was a progressive and substantial disruption in AChR concentration and distribution within the NMJ footprint.

DISCUSSION: Thus, NMJ functional deficits appear at least 6 weeks before motor symptoms in vivo, while structural deficits occur 4 weeks later, and predominantly within NMJs. These data suggest initial therapies focused on rectifying suboptimal NMJ function could produce effective relief of symptoms of weakness.}, } @article {pmid37273142, year = {2023}, author = {Iida, S and Kanouchi, T and Hattori, T and Kanai, K and Nakazato, T and Hattori, N and Yokota, T}, title = {Verification of propagation hypothesis in patients with sporadic hand onset amyotrophic lateral sclerosis.}, journal = {Acta neurologica Belgica}, volume = {123}, number = {4}, pages = {1511-1517}, pmid = {37273142}, issn = {2240-2993}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis ; Retrospective Studies ; Hand ; }, abstract = {OBJECTIVE: If lesions in sporadic amyotrophic lateral sclerosis (ALS) originate from a single focal onset site and spread contiguously by prion-like cell-to-cell propagation at a constant speed, the lesion spread time should be proportional to the anatomical distance. We verify this model in the patients.

METHODS: In 29 sporadic ALS patients with hand onset followed by spread to shoulder and leg, we retrospectively evaluated the inter/intra-regional spread time ratio: time interval of symptoms from hand-to-leg divided by that from hand-to-shoulder. We also obtained the corresponding inter-/intra-regional distance ratios of spinal cord from magnetic resonance imaging of 12 patients, and those of primary motor cortex from coordinates using neuroimaging software.

RESULTS: Inter-/intra-regional spread time ratios ranged from 0.29 to 6.00 (median 1.20). Distance ratios ranged from 1.85 to 2.86 in primary motor cortex and from 5.79 to 8.67 in spinal cord. Taken together with clinical manifestations, of 27 patients with the requisite information available, lesion spreading was consistent with the model in primary motor cortex in 4 (14.8%) patients, and in spinal cord in only 1 (3.7%) patient. However, in more patients (12 of 29 patients: 41.4%), the inter-regional spread times in a long anatomical distance of hand-to-leg were shorter than or equal to the intra-regional spread times in a short anatomical distance of hand-to-shoulder.

CONCLUSION: Contiguous cell-to-cell propagation at a constant speed might not play a major role at least in distant lesion spreading of ALS. Several mechanisms can be responsible for progression in ALS.}, } @article {pmid37272384, year = {2023}, author = {Enriquez de Salamanca Gambara, R and Sanz-García, A and Martín-Conty, JL and Polonio-López, B and Del Pozo Vegas, C and Martín-Rodríguez, F and López-Izquierdo, R}, title = {Long-Term Mortality in Patients Transferred by Emergency Medical Services: Prospective Cohort Study.}, journal = {Prehospital and disaster medicine}, volume = {38}, number = {3}, pages = {352-359}, doi = {10.1017/S1049023X23005800}, pmid = {37272384}, issn = {1945-1938}, mesh = {Adult ; Humans ; Prospective Studies ; *Emergency Medical Services ; Emergency Service, Hospital ; Ambulances ; Risk Factors ; }, abstract = {OBJECTIVE: This study aimed to determine the long-term mortality (one-year follow-up) associated with patients transferred by Emergency Medical Services (EMS), and to reveal the determinants (causes and risk factors).

METHODS: This was a multicenter, prospective, observational, controlled, ambulance-based study of adult patients transferred by ambulance to emergency departments (EDs) from October 2019 through July 2021 for any cause. A total of six Advanced Life Support (ALS) units, 38 Basic Life Support (BLS) units, and five hospitals from Spain were included. Physiological, biochemical, demographic, and reasons for transfer variables were collected. A longitudinal analysis was performed to determine the factors associated to long-term mortality (any cause).

RESULTS: The final cohort included 1,406 patients. The one-year mortality rate was 21.6% (n = 304). Mortality over the first two days reached 5.2% of all the patients; between Day 2 and Day 30, reached 5.3%; and between Day 31 and Day 365, reached 11.1%. Low Glasgow values, elevated lactate levels, elevated blood urea nitrogen (BUN) levels, low oxygen saturation, high respiratory rate, as well as being old and suffering from circulatory diseases and neurological diseases were risk factors for long-term mortality.

CONCLUSION: The quick identification of patients at risk of long-term worsening could provide an opportunity to customize care through specific follow-up.}, } @article {pmid37272348, year = {2024}, author = {Bouvier, L and McKinlay, S and Truong, J and Genge, A and Dupré, N and Dionne, A and Kalra, S and Yunusova, Y}, title = {Speech timing and monosyllabic diadochokinesis measures in the assessment of amyotrophic lateral sclerosis in Canadian French.}, journal = {International journal of speech-language pathology}, volume = {26}, number = {2}, pages = {267-277}, pmid = {37272348}, issn = {1754-9515}, support = {R01 DC017291/DC/NIDCD NIH HHS/United States ; }, mesh = {Humans ; *Speech ; *Amyotrophic Lateral Sclerosis/complications ; Canada ; Speech Production Measurement/methods ; Language ; }, abstract = {PURPOSE: The primary objective of this study was to determine if speech and pause measures obtained using a passage reading task and timing measures from a monosyllabic diadochokinesis (DDK) task differ across speakers of Canadian French diagnosed with amyotrophic lateral sclerosis (ALS) presenting with and without bulbar symptoms, and healthy controls. The secondary objective was to determine if these measures can reflect the severity of bulbar symptoms.

METHOD: A total of 29 Canadian French speakers with ALS (classified as bulbar symptomatic [n = 14] or pre-symptomatic [n = 15]) and 17 age-matched healthy controls completed a passage reading task and a monosyllabic DDK task (/pa/ and /ta/), for up to three follow-up visits. Measures of speaking rate, total duration, speech duration, and pause events were extracted from the passage reading recordings using a semi-automated speech and pause analysis procedure. Manual analysis of DDK recordings provided measures of DDK rate and variability.

RESULT: Group comparisons revealed significant differences (p = < .05) between the symptomatic group and the pre-symptomatic and control groups for all passage measures and DDK rates. Only the DDK rate in /ta/ differentiated the pre-symptomatic and control groups. Repeated measures correlations revealed moderate correlations (rrm = > 0.40; p = < 0.05) between passage measures of total duration, speaking rate, speech duration, and number of pauses, and ALSFRS-R total and bulbar scores, as well as between DDK rate and ALSFRS-R total score.

CONCLUSION: Speech and pause measures in passage and timing measures in monosyllabic DDK tasks might be suitable for monitoring bulbar functional symptoms in French speakers with ALS, but more work is required to identify which measures are sensitive to the earliest stages of the disease.}, } @article {pmid37270090, year = {2023}, author = {Shibahashi, K and Kato, T and Hikone, M and Sugiyama, K}, title = {Identifying individuals satisfying the termination of resuscitation rule but having potential to achieve favourable neurological outcome following out-of-hospital cardiac arrest.}, journal = {Resuscitation}, volume = {190}, number = {}, pages = {109860}, doi = {10.1016/j.resuscitation.2023.109860}, pmid = {37270090}, issn = {1873-1570}, mesh = {Adolescent ; Aged, 80 and over ; Humans ; *Cardiopulmonary Resuscitation ; Decision Support Techniques ; *Emergency Medical Services ; *Out-of-Hospital Cardiac Arrest/therapy ; Registries ; Resuscitation Orders ; Life Support Care ; }, abstract = {AIM: To develop a simple scoring model that identifies individuals satisfying the termination of resuscitation (TOR) rule but having potential to achieve favourable neurological outcome following out-of-hospital cardiac arrest (OHCA).

METHODS: This study analysed the All-Japan Utstein Registry from 1 January 2010 to 31 December 2019. We identified patients satisfying basic life support (BLS) and advanced life support (ALS) TOR rules and determined factors associated with favourable neurological outcome (cerebral performance category scale of 1 or 2) for each cohort using multivariable logistic regression analysis. Scoring models were derived and validated to identify patient subgroups that might benefit from continued resuscitation efforts.

RESULTS: Among 1,695,005 eligible patients, 1,086,092 (64.1%) and 409,498 (24.2%) satisfied BLS and ALS TOR rules, respectively. One month post-arrest, 2038 (0.2%) and 590 (0.1%) patients in the BLS and ALS cohorts, respectively, achieved favourable neurological outcome. A scoring model derived for the BLS cohort (2 points for age <17 years or ventricular fibrillation/ventricular tachycardia rhythm; 1 point for age <80 years, pulseless electrical activity rhythm, or transport time <25 min) effectively stratified the probability of achieving 1-month favourable neurological outcome, with patients scoring <4 having a probability of <1%, whereas those scoring 4, 5, and 6 having probabilities of 1.1%, 7.1%, and 11.1%, respectively. In the ALS cohort, the probability increased with scores; however, it remained <1%.

CONCLUSION: A simple scoring model comprising age, first documented cardiac rhythm, and transport time effectively stratified the likelihood of achieving favourable neurological outcome in patients satisfying the BLS TOR rule.}, } @article {pmid37269968, year = {2023}, author = {Alqahtani, T and Deore, SL and Kide, AA and Shende, BA and Sharma, R and Dadarao Chakole, R and Nemade, LS and Kishor Kale, N and Borah, S and Shrikant Deokar, S and Behera, A and Dhawal Bhandari, D and Gaikwad, N and Kalam Azad, A and Ghosh, A}, title = {Mitochondrial dysfunction and oxidative stress in Alzheimer's disease, and Parkinson's disease, Huntington's disease and Amyotrophic Lateral Sclerosis -An updated review.}, journal = {Mitochondrion}, volume = {71}, number = {}, pages = {83-92}, doi = {10.1016/j.mito.2023.05.007}, pmid = {37269968}, issn = {1872-8278}, mesh = {Humans ; *Parkinson Disease/pathology ; *Alzheimer Disease/pathology ; *Huntington Disease/metabolism ; *Amyotrophic Lateral Sclerosis/pathology ; Oxidative Stress/physiology ; *Neurodegenerative Diseases/metabolism ; Mitochondria/metabolism ; }, abstract = {Misfolded proteins in the central nervous system can induce oxidative damage, which can contribute to neurodegenerative diseases in the mitochondria. Neurodegenerative patients face early mitochondrial dysfunction, impacting energy utilization. Amyloid-ß and tau problems both have an effect on mitochondria, which leads to mitochondrial malfunction and, ultimately, the onset of Alzheimer's disease. Cellular oxygen interaction yields reactive oxygen species within mitochondria, initiating oxidative damage to mitochondrial constituents. Parkinson's disease, linked to oxidative stress, α-synuclein aggregation, and inflammation, results from reduced brain mitochondria activity. Mitochondrial dynamics profoundly influence cellular apoptosis via distinct causative mechanisms. The condition known as Huntington's disease is characterized by an expansion of polyglutamine, primarily impactingthe cerebral cortex and striatum. Research has identified mitochondrial failure as an early pathogenic mechanism contributing to HD's selective neurodegeneration. The mitochondria are organelles that exhibit dynamism by undergoing fragmentation and fusion processes to attain optimal bioenergetic efficiency. They can also be transported along microtubules and regulateintracellular calcium homeostasis through their interaction with the endoplasmic reticulum. Additionally, the mitochondria produce free radicals. The functions of eukaryotic cells, particularly in neurons, have significantly deviated from the traditionally assigned role of cellular energy production. Most of them areimpaired in HD, which may lead to neuronal dysfunction before symptoms manifest. This article summarizes the most important changes in mitochondrial dynamics that come from neurodegenerative diseases including Alzheimer's, Parkinson's, Huntington's and Amyotrophic Lateral Sclerosis. Finally, we discussed about novel techniques that can potentially treat mitochondrial malfunction and oxidative stress in four most dominating neuro disorders.}, } @article {pmid37269231, year = {2024}, author = {Alqallaf, A and Cates, DW and Render, KP and Patel, KA}, title = {Sodium Phenylbutyrate and Taurursodiol: A New Therapeutic Option for the Treatment of Amyotrophic Lateral Sclerosis.}, journal = {The Annals of pharmacotherapy}, volume = {58}, number = {2}, pages = {165-173}, doi = {10.1177/10600280231172802}, pmid = {37269231}, issn = {1542-6270}, mesh = {United States ; Humans ; *Amyotrophic Lateral Sclerosis/drug therapy ; Phenylbutyrates/adverse effects ; }, abstract = {OBJECTIVE: To review the safety and efficacy of sodium phenylbutyrate and taurursodiol (SP + T) in slowing progression of amyotrophic lateral sclerosis (ALS) compared with pre-existing therapies.

DATA SOURCES: A PubMed (from January 1, 2009, to April 13, 2023) and ClinicalTrials.gov search conducted using sodium phenylbutyrate, taurursodiol, AMX0035, riluzole, and edaravone. Additional articles were identified by hand from references.

This included English-language articles evaluating SP + T efficacy or safety in humans for decreasing neuronal death and slowing the progression of ALS.

DATA SYNTHESIS: In one phase II clinical trial that encompassed an open-label extension phase, disease severity, assessed by the rate of decline in overall score on the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised with higher scores indicating more functional ability, was -1.24 points per month with active drug and -1.66 points per month with placebo (difference, 0.42 points per month; 95% CI, 0.03-0.81; P = 0.03). Post hoc analysis found survival benefit of median 4.8 months with active medication compared with placebo.

SP + T is a new US Food and Drug Administration-approved oral suspension for the treatment of ALS. Patients who received active medication through the phase II trial showed decreased rates of disease progression. Overall, SP + T could be considered a potential agent for the treatment of ALS which has a high unmet need.

CONCLUSION: SP + T is an option for the treatment of ALS; however, additional data regarding efficacy in phase III trials with long-term safety profile considerations, as well as trials to compare current therapy with SP + T, are needed.}, } @article {pmid37269166, year = {2023}, author = {Vucic, S}, title = {Clinical utility of far field motor potentials in amyotrophic lateral sclerosis.}, journal = {Muscle & nerve}, volume = {68}, number = {3}, pages = {237-239}, doi = {10.1002/mus.27852}, pmid = {37269166}, issn = {1097-4598}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis ; Evoked Potentials ; }, } @article {pmid37268555, year = {2024}, author = {Fakim, H and Vande Velde, C}, title = {The implications of physiological biomolecular condensates in amyotrophic lateral sclerosis.}, journal = {Seminars in cell & developmental biology}, volume = {156}, number = {}, pages = {176-189}, doi = {10.1016/j.semcdb.2023.05.006}, pmid = {37268555}, issn = {1096-3634}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism ; Biomolecular Condensates ; DNA-Binding Proteins/genetics/metabolism ; *Neurodegenerative Diseases/metabolism ; Mutation/genetics ; RNA ; }, abstract = {In recent years, there has been an emphasis on the role of phase-separated biomolecular condensates, especially stress granules, in neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS). This is largely due to several ALS-associated mutations occurring in genes involved in stress granule assembly and observations that pathological inclusions detected in ALS patient neurons contain stress granule proteins, including the ALS-linked proteins TDP-43 and FUS. However, protein components of stress granules are also found in numerous other phase-separated biomolecular condensates under physiological conditions which are inadequately discussed in the context of ALS. In this review, we look beyond stress granules and describe the roles of TDP-43 and FUS in physiological condensates occurring in the nucleus and neurites, such as the nucleolus, Cajal bodies, paraspeckles and neuronal RNA transport granules. We also discuss the consequences of ALS-linked mutations in TDP-43 and FUS on their ability to phase separate into these stress-independent biomolecular condensates and perform their respective functions. Importantly, biomolecular condensates sequester multiple overlapping protein and RNA components, and their dysregulation could contribute to the observed pleiotropic effects of both sporadic and familial ALS on RNA metabolism.}, } @article {pmid37268333, year = {2023}, author = {Chen, X and Zhou, L and Cui, C and Sun, J}, title = {Evolving markers in amyotrophic lateral sclerosis.}, journal = {Advances in clinical chemistry}, volume = {114}, number = {}, pages = {225-246}, doi = {10.1016/bs.acc.2023.02.002}, pmid = {37268333}, issn = {2162-9471}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/therapy ; *Neurodegenerative Diseases ; Motor Neurons/physiology ; Prognosis ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a relatively rare but fatal neurodegenerative disease with the progressive loss of both upper and lower motor neurons. Although electromyography, imaging and multi-omics technologies have suggested numerous functional, structural, circulating and microbiota markers for ALS, no clinically validated markers have, as yet, been identified. Here we summarize the advances to characterize markers underlying ALS pathophysiology as well as their potential use in diagnosis, prognosis and therapy.}, } @article {pmid37267913, year = {2023}, author = {Morimoto, S and Takahashi, S and Ito, D and Daté, Y and Okada, K and Kato, C and Nakamura, S and Ozawa, F and Chyi, CM and Nishiyama, A and Suzuki, N and Fujimori, K and Kondo, T and Takao, M and Hirai, M and Kabe, Y and Suematsu, M and Jinzaki, M and Aoki, M and Fujiki, Y and Sato, Y and Suzuki, N and Nakahara, J and , and Okano, H}, title = {Phase 1/2a clinical trial in ALS with ropinirole, a drug candidate identified by iPSC drug discovery.}, journal = {Cell stem cell}, volume = {30}, number = {6}, pages = {766-780.e9}, doi = {10.1016/j.stem.2023.04.017}, pmid = {37267913}, issn = {1875-9777}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy ; Indoles/adverse effects/pharmacology ; *Induced Pluripotent Stem Cells ; Motor Neurons ; }, abstract = {iPSC-based drug discovery led to a phase 1/2a trial of ropinirole in ALS. 20 participants with sporadic ALS received ropinirole or placebo for 24 weeks in the double-blind period to evaluate safety, tolerability, and therapeutic effects. Adverse events were similar in both groups. During the double-blind period, muscle strength and daily activity were maintained, but a decline in the ALSFRS-R, which assesses the functional status of ALS patients, was not different from that in the placebo group. However, in the open-label extension period, the ropinirole group showed significant suppression of ALSFRS-R decline and an additional 27.9 weeks of disease-progression-free survival. iPSC-derived motor neurons from participants showed dopamine D2 receptor expression and a potential involvement of the SREBP2-cholesterol pathway in therapeutic effects. Lipid peroxide represents a clinical surrogate marker to assess disease progression and drug efficacy. Limitations include small sample sizes and high attrition rates in the open-label extension period, requiring further validation.}, } @article {pmid37267911, year = {2023}, author = {Mazzini, L and De Marchi, F}, title = {iPSC-based research in ALS precision medicine.}, journal = {Cell stem cell}, volume = {30}, number = {6}, pages = {748-749}, doi = {10.1016/j.stem.2023.05.008}, pmid = {37267911}, issn = {1875-9777}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy ; *Induced Pluripotent Stem Cells/physiology ; Precision Medicine ; Motor Neurons ; }, abstract = {Clinical trials in amyotrophic lateral sclerosis (ALS) are challenged by the lack of pre-clinical models and biomarkers of disease onset and progression. In this issue, Morimoto et al. use induced pluripotent stem cell (iPSC)-derived motor neurons from patients with ALS to study therapeutic mechanisms of ropinirole in a clinical trial and identify treatment responders.}, } @article {pmid37266922, year = {2024}, author = {Parra-Cantu, C and Martinez-Thompson, JM and Linch, FB and Welch, TL and Chou, CZ and Pattinson, AK and Staff, NP and Neisen, M}, title = {Radiologically Inserted Gastrostomy Tube Placement Guided by the Assessment and Primary Palliative Care Provided by an Amyotrophic Lateral Sclerosis Multidisciplinary Clinic: A Single-Arm Retrospective Clinical Study.}, journal = {The American journal of hospice & palliative care}, volume = {41}, number = {5}, pages = {516-526}, doi = {10.1177/10499091231180553}, pmid = {37266922}, issn = {1938-2715}, mesh = {Humans ; Gastrostomy/methods ; Retrospective Studies ; *Amyotrophic Lateral Sclerosis/therapy ; Palliative Care ; *Neurodegenerative Diseases ; Quality of Life ; Treatment Outcome ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with a median survival of about 3 years. An ALS multidisciplinary team can provide primary palliative care and improve outcomes and quality of life for patients. Feeding tube insertion may be considered for patients with significant weight loss, or respiratory insufficiency. While radiologically inserted gastrostomy (RIG) tube placement may be an option, further studies are required to determine its best timing and appropriateness. This study's objectives were to evaluate the feasibility and outcomes of RIG tube placement in ALS patients over a 90-day follow-up period through the assessment and primary palliative care provided by the multidisciplinary team. This retrospective study reviewed the placement of 16 or 18 French RIG-tube without intubation or endoscopy for 36 ALS patients at a single center between April 2019 and December 2021. Measures included ALS Functional Rating Scale-Revised (ALSFRS-R) scores to determine the ALS stage. Demographic, clinical, procedural, and follow-up data were reviewed. Results showed that the RIG tube placement had a low rate of minor adverse events (11%) and no major procedure-related adverse events. The mean ALSFRS-R score at the time of procedure in subjects who died within 90 days was lower than of those alive beyond 90 days (P = .04). This study found that RIG-tube placement is a safe and effective way to manage dysphagia in ALS patients and highlights the importance of educating members of the multidisciplinary clinic in palliative care principles to determine the appropriateness of RIG tube placement.}, } @article {pmid37266849, year = {2024}, author = {Ugale, V and Deshmukh, R and Lokwani, D and Narayana Reddy, P and Khadse, S and Chaudhari, P and Kulkarni, PP}, title = {GluN2B subunit selective N-methyl-D-aspartate receptor ligands: Democratizing recent progress to assist the development of novel neurotherapeutics.}, journal = {Molecular diversity}, volume = {28}, number = {3}, pages = {1765-1792}, pmid = {37266849}, issn = {1573-501X}, mesh = {*Receptors, N-Methyl-D-Aspartate/metabolism/antagonists & inhibitors ; Humans ; Ligands ; Animals ; Structure-Activity Relationship ; Protein Subunits/metabolism/chemistry ; }, abstract = {N-methyl-D-aspartate receptors (NMDARs) play essential roles in vital aspects of brain functions. NMDARs mediate clinical features of neurological diseases and thus, represent a potential therapeutic target for their treatments. Many findings implicated the GluN2B subunit of NMDARs in various neurological disorders including epilepsy, ischemic brain damage, and neurodegenerative disorders such as Parkinson's disease, Alzheimer's disease, Huntington's chorea, and amyotrophic lateral sclerosis. Although a large amount of information is growing consistently on the importance of GluN2B subunit, however, limited recent data is available on how subunit-selective ligands impact NMDAR functions, which blunts the ability to render the diagnosis or craft novel treatments tailored to patients. To bridge this gap, we have focused on and summarized recently reported GluN2B selective ligands as emerging subunit-selective antagonists and modulators of NMDAR. Herein, we have also presented an overview of the structure-function relationship for potential GluN2B/NMDAR ligands with their binding sites and connection to CNS functionalities. Understanding of design rules and roles of GluN2B selective compounds will provide the link to medicinal chemists and neuroscientists to explore novel neurotherapeutic strategies against dysfunctions of glutamatergic neurotransmission.}, } @article {pmid37266403, year = {2023}, author = {Petersen, RB and Walter, B}, title = {Editorial: Insights into Parkinson's disease and aging related movement disorders.}, journal = {Frontiers in aging neuroscience}, volume = {15}, number = {}, pages = {1193197}, pmid = {37266403}, issn = {1663-4365}, } @article {pmid37265463, year = {2023}, author = {Gagliardi, D and Ripellino, P and Meneri, M and Del Bo, R and Antognozzi, S and Comi, GP and Gobbi, C and Ratti, A and Ticozzi, N and Silani, V and Ronchi, D and Corti, S}, title = {Clinical and molecular features of patients with amyotrophic lateral sclerosis and SOD1 mutations: a monocentric study.}, journal = {Frontiers in neurology}, volume = {14}, number = {}, pages = {1169689}, pmid = {37265463}, issn = {1664-2295}, abstract = {INTRODUCTION: SOD1 was the first gene associated with both familial and sporadic forms of amyotrophic lateral sclerosis (ALS) and is the second most mutated gene in Caucasian ALS patients. Given their high clinical and molecular heterogeneity, a detailed characterization of SOD1-ALS patients could improve knowledge about the natural history of this disease. Here, the authors aimed to provide a clinical and molecular description of a monocentric cohort of SOD1-ALS patients.

METHODS: Amyotrophic lateral sclerosis (ALS) patients referring to the neurology unit of our center between 2008 and 2021 were clinically assessed and underwent molecular testing for SOD1. Segregation studies in available family members and in silico analysis were performed to sustain the pathogenicity of the identified SOD1 variants.

RESULTS: Among the 576 patients in our cohort, we identified 19 individuals harboring a mutation in SOD1 (3.3%), including 15 (78.9%) with a familial and four (21.1%) with a sporadic form. The spinal onset of the disease was observed in all patients, and survival was extremely variable, ranging from 8 months to over 30 years. Twelve different SOD1 missense variants were identified in our cohort, including one novel mutation (p.Pro67Leu).

DISCUSSION: In the present series, we provided the first description of an Italian monocentric cohort of SOD1-ALS patients, and we expanded the repertoire of SOD1 mutations. Our cohort presents several remarkable features, including variable expressivity in the same family, atypical presentation (ataxia, cognitive impairment, and other extra-motor symptoms), and different modes of inheritance of a given mutation in the same family. Given the recent authorization of SOD1-directed antisense oligonucleotide for use in SOD1-ALS patients, we recommend prompt screening for SOD1 mutations in novel ALS patients with familiar or sporadic presentations.}, } @article {pmid37265174, year = {2023}, author = {Tabor Gray, L and Locatelli, E and Vasilopoulos, T and Wymer, J and Plowman, EK}, title = {Dextromethorphan/quinidine for the treatment of bulbar impairment in amyotrophic lateral sclerosis.}, journal = {Annals of clinical and translational neurology}, volume = {10}, number = {8}, pages = {1296-1304}, pmid = {37265174}, issn = {2328-9503}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/complications/drug therapy ; Dextromethorphan/pharmacology/therapeutic use ; Quinidine/pharmacology/therapeutic use ; Deglutition ; Speech ; }, abstract = {OBJECTIVE: No efficacious treatments exist to improve or prolong bulbar functions of speech and swallowing in persons with amyotrophic lateral sclerosis (pALS). This study evaluated the short-term impact of dextromethorphan/quinidine (DMQ) treatment on speech and swallowing function in pALS.

METHODS: This was a cohort trial conducted between August 2019 to August 2021 in pALS with a confirmed diagnosis of probable-definite ALS (El-Escorial Criteria-revisited) and bulbar impairment (ALS Functional Rating Scale score ≤ 10 and speaking rate ≤ 140 words per minute) who were DMQ naïve. Efficacy of DMQ was assessed via pre-post change in the ALS Functional Rating Scale-Revised bulbar subscale and validated speech and swallowing outcomes. Paired t-tests, Fisher's exact, and χ[2] tests were conducted with alpha at 0.05.

RESULTS: Twenty-eight pALS enrolled, and 24 participants completed the 28-day trial of DMQ. A significant increase in ALSFRS-R bulbar subscale score pre- (7.47 ± 1.98) to post- (8.39 ± 1.79) treatment was observed (mean difference: 0.92, 95% CI: 0.46-1.36, p < 0.001). Functional swallowing outcomes improved, with a reduction in unsafe (75% vs. 44%, p = 0.003) and inefficient swallowing (67% vs. 58%, p = 0.002); the relative speech event duration in a standard reading passage increased, indicating a greater duration of uninterrupted speech (mean difference: 0.33 s, 95% CI: 0.02-0.65, p = 0.035). No differences in diadochokinetic rate or speech intelligibility were observed (p > 0.05).

INTERPRETATION: Results of this study provide preliminary evidence that DMQ pharmacologic intervention may have the potential to improve or maintain bulbar function in pALS.}, } @article {pmid37263460, year = {2023}, author = {Punessen, NC and Pena, C and Sandberg, A and Koza, LA and Linseman, DA}, title = {A novel anti-apoptotic role for Cdc42/ACK-1 signaling in neurons.}, journal = {Molecular and cellular neurosciences}, volume = {126}, number = {}, pages = {103865}, doi = {10.1016/j.mcn.2023.103865}, pmid = {37263460}, issn = {1095-9327}, mesh = {Rats ; Animals ; *Protein-Tyrosine Kinases/metabolism ; *rho GTP-Binding Proteins/metabolism/pharmacology ; Neurons/metabolism ; Apoptosis/physiology ; }, abstract = {Neurodegenerative diseases such as amyotrophic lateral sclerosis, Alzheimer's and Parkinson's disease are caused by a progressive and aberrant destruction of neurons in the brain and spinal cord. These disorders lack effective long-term treatments that impact the underlying mechanisms of pathogenesis and as a result, existing options focus primarily on alleviating symptomology. Dysregulated programmed cell death (i.e., apoptosis) is a significant contributor to neurodegeneration, and is controlled by a number of different factors. Rho family GTPases are molecular switches with recognized importance in proper neuronal development and migration that have more recently emerged as central regulators of apoptosis and neuronal survival. Here, we investigated a role for the Rho GTPase family member, Cdc42, and its downstream effectors, in neuronal survival and apoptosis. We initially induced apoptosis in primary cultures of rat cerebellar granule neurons (CGNs) by removing both growth factor-containing serum and depolarizing potassium from the cell medium. We then utilized both chemical inhibitors and adenoviral shRNA targeted to Cdc42 to block the function of Cdc42 or its downstream effectors under either control or apoptotic conditions. Our in vitro studies demonstrate that functional inhibition of Cdc42 or its downstream effector, activated Cdc42-associated tyrosine kinase-1 (ACK-1), had no adverse effects on CGN survival under control conditions, but significantly sensitized neurons to cell death under apoptotic conditions. In conclusion, our results suggest a key pro-survival role for Cdc42/ACK-1 signaling in neurons, particularly in regulating neuronal susceptibility to pro-apoptotic stress such as that observed in neurodegenerative disorders.}, } @article {pmid37263278, year = {2025}, author = {Guler, Y}, title = {Clinical and pathological risk factors for tumour recurrence and upstaging in second TURBT for patients with NMIBC: a systematic review and meta-analysis.}, journal = {Aktuelle Urologie}, volume = {56}, number = {1}, pages = {30-40}, doi = {10.1055/a-2063-3144}, pmid = {37263278}, issn = {1438-8820}, mesh = {Humans ; *Neoplasm Recurrence, Local/pathology ; Risk Factors ; *Urinary Bladder Neoplasms/pathology/surgery ; Neoplasm Staging ; Non-Muscle Invasive Bladder Neoplasms ; }, abstract = {UNLABELLED: ZIEL: Offenlegung signifikanter Risikofaktoren durch Identifizierung gepoolter Effektschätzungsstatistiken in einer systemischen Überprüfung und Metaanalyse klinischer und pathologischer Risikofaktoren, die ein Tumorrezidiv und ein Upstaging auf eine zweite TURBT bei Patienten mit hochgradigem NMIBC vorhersagen.

MATERIAL-METHODE: Alle Datenquellen wurden umfassend bis Oktober 2022 untersucht. Die Daten wurden aus den relevanten Studien extrahiert und mit der Software RevMan analysiert. In einem inversen Varianzmodell mit zufälligen und festen Effekten werden Odds Ratio (OR)-Werte mit 95%-Konfidenzintervallen [95%-KI] angegeben.

ERGEBNISSE: Der Review umfasste insgesamt 18 Studien und 4548 Patienten. Gemäß den gepoolten Effektschätzern waren Carcinoma in situ (CIS), Tumorgrad, Multiplizität und Chirurgenfaktoren signifikante Risikofaktoren. Die gepoolten Effektschätzungen für das Tumorstadium und die Tumormorphologie waren sehr nahe an der Signifikanz. Für CIS, Grad, Multiplizität und Chirurgenfaktor, OR, IVR oder IVF [95%-KI] waren die p- und I2-Werte 1,8 [1,1, 3,0], 0,03, 75%; 2 [1,1, 3,4], 0,02, 53%; 1,3 [1,2, 1,6], <0,01, 40%; und 2 [1,4, 3], <0,01, 66%.

SCHLUSSFOLGERUNGEN: Als Ergebnis der ersten TURBT; Eine zweite TURBT sollte in den 2-6 Wochen der postoperativen Phase für Patienten mit hochgradigem, begleitendem CIS, multipler, solider Morphologie, DM(-) im pathologischen Präparat und NMIBC, das von Trainern/Juniorchirurgen operiert wird, geplant werden.}, } @article {pmid37263249, year = {2023}, author = {Balamurugan, D and Nayak, C and Chattopadhyay, A and Karuppusamy, A and Ambrose, MM and Kumar, A and Singh, NK and Koley, M and Saha, S}, title = {Individualized Homeopathic Medicines in the Treatment of Psoriasis Vulgaris: Double-Blind, Randomized, Placebo-Controlled Trial.}, journal = {Complementary medicine research}, volume = {30}, number = {4}, pages = {317-331}, doi = {10.1159/000530180}, pmid = {37263249}, issn = {2504-2106}, mesh = {Humans ; *Psoriasis/drug therapy ; Double-Blind Method ; *Homeopathy ; India ; }, abstract = {INTRODUCTION: Psoriasis is a chronic inflammatory skin disorder, affecting the trunk and extensor surfaces of the limbs and scalp predominantly. Worldwide prevalence ranges between 0.1 and 11.4%, and in India between 0.4 and 2.8%; this creates a serious health burden. Psoriasis remains a frequently encountered condition in homeopathy practice, but there is a dearth of conclusive efficacy data supporting its use.

METHODS: This 6-month, double-blind, randomized trial was conducted on 51 patients suffering from psoriasis at the National Institute of Homoeopathy, India. Patients were randomized to receive either individualized homeopathic medicines (IHMs; n = 25) in LM potencies or identical-looking placebos (n = 26). Psoriasis area and severity index (PASI; primary), psoriasis disability index (PDI), and dermatological life quality index (DLQI; secondary) were measured at baseline and every 2 months, up to 6 months. The intention-to-treat sample was analyzed using a two-way repeated measure analysis of variance.

RESULTS: Although intragroup changes were significant in both groups in the outcome measures, improvements were significantly higher in the IHMs group than in placebos in PASI scores after 6 months of intervention (F1, 49 = 10.448, p = 0.002). DLQI daily activity subscale scores also yielded similar significant results favoring IHMs against placebos after 6 months (F1, 49 = 5.480, p = 0.023). Improvement in PDI total (F1, 49 = 0.063, p = 0.803), DLQI total (F1, 49 = 1.371, p = 0.247), and all remaining subscales were higher in the IHMs group than placebos after 6 months, but nonsignificant statistically. Calcarea carbonica, Mercurius solubilis, Arsenicum album, and Petroleum were the most frequently prescribed medicines.

CONCLUSIONS: IHMs exhibited better results than placebos in the treatment of psoriasis. Further research is warranted.

UNLABELLED: EinleitungPsoriasis ist eine chronisch entzündliche Hauterkrankung, die vor allem den Körperstamm und die Streckseiten der Extremitäten sowie die Kopfhaut betrifft. Die weltweite Prävalenz liegt zwischen 0,1 und 11,4% und in Indien zwischen 0,4 und 2,8%, was sie zu einer erheblichen Belastung für das Gesundheitssystem macht. In der homöopathischen Praxis ist die Psoriasis nach wie vor häufig anzutreffen, doch mangelt es an schlüssigen Wirksamkeitsdaten, die deren Anwendung stützen.MethodenDiese sechsmonatige, doppelblinde, randomisierte Studie wurde mit 51 Psoriasis-Patienten am National Institute of Homoeopathy in Indien durchgeführt. Die Patienten erhielten randomisiert entweder individualisierte homöopathische Arzneimittel (individualized homeopathic medicines, IHMs; n = 25) in LM-Potenzen oder identisch aussehende Placebos (n = 26). Der Psoriasis Area and Severity Index (PASI; primär), der Psoriasis Disability Index (PDI) und der Dermatological Life Quality Index (DLQI; sekundär) wurden bei Baseline und anschließend alle zwei Monate für bis zu sechs Monate gemessen. Die Analyse der Intention-to-Treat-Stichprobe erfolgte mittels zweifaktorieller Varianzanalyse mit wiederholten Messungen.ErgebnisseZwar waren in beiden Gruppen die gruppeninternen Veränderungen bei den Zielkriterien signifikant, doch fielen die Verbesserungen der PASI-Werte nach der sechsmonatigen Intervention in der IHM-Gruppe signifikant höher aus als in der Placebogruppe (F1, 49 = 10,448, p = 0,002), und die Werte der DLQI-Subskala für die tägliche Aktivität zeigten nach 6 Monaten ähnliche signifikante Ergebnisse zugunsten der IHMs gegenüber Placebo (F1, 49 = 5,480, p = 0,023). Die Verbesserungen beim PDI-Gesamt-Score (F1, 49 = 0,063, p = 0,803), beim DLQI-Gesamt-Score (F1, 49 = 1,371, p = 0,247) und bei den anderen Subskalen waren nach 6 Monaten in der IHM-Gruppe höher als in der Placebo-Gruppe, erreichten jedoch keine statistische Signifikanz. Calcarea carbonica, Mercurius solubilis, Arsenicum album und Petroleum waren die am häufigsten verordneten Arzneimittel.SchlussfolgerungenDie IHMs zeigten in der Behandlung der Psoriasis bessere Ergebnisse als Placebo. Weitere Untersuchungen sind erforderlich.}, } @article {pmid37261630, year = {2023}, author = {Zhu, Y and Li, M and He, Z and Pang, X and Du, R and Yu, W and Zhang, J and Bai, J and Wang, J and Huang, X}, title = {Evaluating the causal association between microRNAs and amyotrophic lateral sclerosis.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {44}, number = {10}, pages = {3567-3575}, pmid = {37261630}, issn = {1590-3478}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/epidemiology/genetics ; Genome-Wide Association Study ; *MicroRNAs/genetics/metabolism ; *Circulating MicroRNA/genetics ; Biomarkers ; }, abstract = {BACKGROUND: Currently, miRNAs are involved in the development of amyotrophic lateral sclerosis (ALS), and identifying circulating miRNAs that are causally associated with ALS risk as biomarkers is imperative.

METHODS: We performed a two-sample Mendelian randomization study to evaluate the causal relationship between miRNAs and ALS. Our analysis was conducted using summary statistics from miRNA expression quantitative loci (eQTL) data of the Framingham Heart Study and ALS genome-wide association studies data. Another independent miRNA data was used to further validate.

RESULTS: We identified eight unique miRNAs that were causally associated with ALS risk. Using expression data of miRNAs from an independent study, we validated three high-confidence miRNAs, namely hsa-miR-27b-3p, hsa-miR-139-5p, and hsa-miR-152-3p, which might have a potential causal effect on ALS risk.

CONCLUSION: We suggested that higher levels of hsa-miR-27b-3p and hsa-miR-139-5p had protective effects on ALS, whereas higher levels of hsa-miR-152-3p might act as a risk factor for ALS. The analytical framework presented in this study helps to understand the role of miRNAs in the development of ALS and to identify the biomarkers for ALS risk.}, } @article {pmid37260726, year = {2023}, author = {Chavan, M and Singh, A and Bathvar, PK and Mehta, ST and Qadree, AK and Dhakal, S}, title = {Bulbar onset amyotrophic lateral sclerosis with more evident symptoms in the left hemibody: a case report.}, journal = {Oxford medical case reports}, volume = {2023}, number = {5}, pages = {omad045}, pmid = {37260726}, issn = {2053-8855}, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive, degenerative neuromuscular condition. The procedure and difficulties involved in the clinical diagnosis of ALS have been the subject of numerous investigations. The understanding of the genetics and the epigenetics of the disease is still at infancy with several missing links. We present a case report of a 73-year-old woman suffering from bulbar onset ALS with a 4-month history of progressive dysphagia and dyspnea. She displayed tongue fasciculations and muscle atrophy. The bilateral palmomental reflexes, snout reflex, Hoffman, Babinski, diminished gag reflex, bilateral clonus and wild mood swings confirmed the neurodegenerative condition of the patient. The diagnosis of ALS can be challenging; therefore, the data presented may be useful to investigate its characteristics of the onset and to improve the understanding of the aspects of differentiation from other neurodegenerative disorders.}, } @article {pmid37260495, year = {2023}, author = {Garcia-Guerra, A and Ellerington, R and Gaitzsch, J and Bath, J and Kye, M and Varela, MA and Battaglia, G and Wood, MJA and Manzano, R and Rinaldi, C and Turberfield, AJ}, title = {A modular RNA delivery system comprising spherical nucleic acids built on endosome-escaping polymeric nanoparticles.}, journal = {Nanoscale advances}, volume = {5}, number = {11}, pages = {2941-2949}, pmid = {37260495}, issn = {2516-0230}, support = {205162/Z/16/Z/WT_/Wellcome Trust/United Kingdom ; MC_PC_16056/MRC_/Medical Research Council/United Kingdom ; }, abstract = {Nucleic acid therapeutics require delivery systems to reach their targets. Key challenges to be overcome include avoidance of accumulation in cells of the mononuclear phagocyte system and escape from the endosomal pathway. Spherical nucleic acids (SNAs), in which a gold nanoparticle supports a corona of oligonucleotides, are promising carriers for nucleic acids with valuable properties including nuclease resistance, sequence-specific loading and control of receptor-mediated endocytosis. However, SNAs accumulate in the endosomal pathway and are thus vulnerable to lysosomal degradation or recycling exocytosis. Here, an alternative SNA core based on diblock copolymer PMPC25-PDPA72 is investigated. This pH-sensitive polymer self-assembles into vesicles with an intrinsic ability to escape endosomes via osmotic shock triggered by acidification-induced disassembly. DNA oligos conjugated to PMPC25-PDPA72 molecules form vesicles, or polymersomes, with DNA coronae on luminal and external surfaces. Nucleic acid cargoes or nucleic acid-tagged targeting moieties can be attached by hybridization to the coronal DNA. These polymeric SNAs are used to deliver siRNA duplexes against C9orf72, a genetic target with therapeutic potential for amyotrophic lateral sclerosis, to motor neuron-like cells. By attaching a neuron-specific targeting peptide to the PSNA corona, effective knock-down is achieved at doses of 2 particles per cell.}, } @article {pmid37259916, year = {2023}, author = {Berth, SH and Lloyd, TE}, title = {Disruption of axonal transport in neurodegeneration.}, journal = {The Journal of clinical investigation}, volume = {133}, number = {11}, pages = {}, pmid = {37259916}, issn = {1558-8238}, support = {K08 NS118123/NS/NINDS NIH HHS/United States ; R01 NS082563/NS/NINDS NIH HHS/United States ; R01 NS094239/NS/NINDS NIH HHS/United States ; P30 NS050274/NS/NINDS NIH HHS/United States ; }, mesh = {Humans ; Axonal Transport/physiology ; *Neurodegenerative Diseases/metabolism ; Neurons/metabolism ; *Alzheimer Disease/metabolism ; *Parkinson Disease/metabolism ; }, abstract = {Neurons are markedly compartmentalized, which makes them reliant on axonal transport to maintain their health. Axonal transport is important for anterograde delivery of newly synthesized macromolecules and organelles from the cell body to the synapse and for the retrograde delivery of signaling endosomes and autophagosomes for degradation. Dysregulation of axonal transport occurs early in neurodegenerative diseases and plays a key role in axonal degeneration. Here, we provide an overview of mechanisms for regulation of axonal transport; discuss how these mechanisms are disrupted in neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, Huntington's disease, hereditary spastic paraplegia, amyotrophic lateral sclerosis, and Charcot-Marie-Tooth disease; and discuss therapeutic approaches targeting axonal transport.}, } @article {pmid37259156, year = {2023}, author = {Ionescu, A and Altman, T and Perlson, E}, title = {Looking for answers far away from the soma-the (un)known axonal functions of TDP-43, and their contribution to early NMJ disruption in ALS.}, journal = {Molecular neurodegeneration}, volume = {18}, number = {1}, pages = {35}, pmid = {37259156}, issn = {1750-1326}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism ; Axons/metabolism ; *DNA-Binding Proteins/metabolism ; *Neurodegenerative Diseases/metabolism ; Neuromuscular Junction ; }, abstract = {Axon degeneration and Neuromuscular Junction (NMJ) disruption are key pathologies in the fatal neurodegenerative disease Amyotrophic Lateral Sclerosis (ALS). Despite accumulating evidence that axons and NMJs are impacted at a very early stage of the disease, current knowledge about the mechanisms leading to their degeneration remains elusive. Cytoplasmic mislocalization and accumulation of the protein TDP-43 are considered key pathological hallmarks of ALS, as they occur in ~ 97% of ALS patients, both sporadic and familial. Recent studies have identified pathological accumulation of TDP-43 in intramuscular nerves of muscle biopsies collected from pre-diagnosed, early symptomatic ALS patients. These findings suggest a gain of function for TDP-43 in axons, which might facilitate early NMJ disruption. In this review, we dissect the process leading to axonal TDP-43 accumulation and phosphorylation, discuss the known and hypothesized roles TDP-43 plays in healthy axons, and review possible mechanisms that connect TDP-43 pathology to the axon and NMJ degeneration in ALS.}, } @article {pmid37258447, year = {2023}, author = {Liu, J and Duan, W and Deng, Y and Zhang, Q and Li, R and Long, J and Ahmed, W and Gu, C and Qiu, Y and Cai, H and Hu, Y and Chen, L}, title = {New Insights into Molecular Mechanisms Underlying Neurodegenerative Disorders.}, journal = {Journal of integrative neuroscience}, volume = {22}, number = {3}, pages = {58}, doi = {10.31083/j.jin2203058}, pmid = {37258447}, issn = {0219-6352}, support = {2022YFA1104900//National Key R&D Program of China/ ; 2022YFA1104904//National Key R&D Program of China/ ; 2021A1515010013//Natural Science Foundation of Guangdong Province/ ; 2021ZDZX2011//Department of Education of Guangdong Province/ ; 20221275//Traditional Chinese Medicine Bureau of Guangdong Province/ ; 202201011760//Guangzhou Municipal Science and Technology Project/ ; 1202101003//President Foundation of Integrated Hospital of Traditional Chinese Medicine of Southern Medical University/ ; 1202103007//President Foundation of Integrated Hospital of Traditional Chinese Medicine of Southern Medical University/ ; }, mesh = {Humans ; Quality of Life ; *Neurodegenerative Diseases/metabolism ; *Alzheimer Disease/metabolism ; *Parkinson Disease/etiology/therapy/metabolism ; Oxidative Stress ; }, abstract = {As a large and heterogeneous group of disorders, neurodegenerative diseases are characterized by the progressive loss of structure or function in neurons, finally leading to neuronal death. Neurodegenerative diseases cause serious threat to a patient's quality of life and the most common are Alzheimer's disease and Parkinson's disease. Currently, little is known of the detailed etiology of these disorders; as such, there are no effective treatments available. Furthermore, the lack of targeted, effective, and resolvable therapy for neurodegenerative diseases, represents an expanding research field for the discovery of new therapeutic strategies. Investigations of the potential pathogenesis of neurodegenerative diseases will become the basis of preventing the occurrence and development of neurodegenerative diseases and finding effective therapies. Existing theories and mechanisms, such as genetic and environmental factors, abnormal protein accumulation, and oxidative stress, are intricately associated with each other. However, there is no molecular theory that can entirely explain the pathological processes underlying neurodegenerative diseases. Due to the development of experimental technology and the support of multidisciplinary integration, it has been possible to perform more in-depth research on potential targets for neurodegenerative diseases and there have been many exciting discoveries in terms of original theories and underlying mechanisms. With this review, we intend to review the existing literature and provide new insights into the molecular mechanisms underlying neurodegenerative diseases.}, } @article {pmid37257946, year = {2023}, author = {Idera, A and Sharkey, LM and Kurauchi, Y and Kadoyama, K and Paulson, HL and Katsuki, H and Seki, T}, title = {Wild-type and pathogenic forms of ubiquilin 2 differentially modulate components of the autophagy-lysosome pathways.}, journal = {Journal of pharmacological sciences}, volume = {152}, number = {3}, pages = {182-192}, doi = {10.1016/j.jphs.2023.05.002}, pmid = {37257946}, issn = {1347-8648}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology ; Adaptor Proteins, Signal Transducing/genetics ; Autophagy/genetics ; Mutation ; Autophagy-Related Proteins/genetics/metabolism ; Transcription Factors/metabolism ; Lysosomes/metabolism/pathology ; }, abstract = {Missense mutations of ubiquilin 2 (UBQLN2) have been identified to cause X-linked amyotrophic lateral sclerosis (ALS). Proteasome-mediated protein degradation is reported to be impaired by ALS-associated mutations of UBQLN2. However, it remains unknown how these mutations affect autophagy-lysosome protein degradation, which consists of macroautophagy (MA), microautophagy (mA), and chaperone-mediated autophagy (CMA). Using a CMA/mA fluorescence reporter we found that overexpression of wild-type UBQLN2 impairs CMA. Conversely, knockdown of endogenous UBQLN2 increases CMA activity, suggesting that normally UBQLN2 negatively regulates CMA. ALS-associated mutant forms of UBQLN2 exacerbate this impairment of CMA. Using cells stably transfected with wild-type or ALS-associated mutant UBQLN2, we further determined that wild-type UBQLN2 increased the ratio of LAMP2A (a CMA-related protein) to LAMP1 (a lysosomal protein). This could represent a compensatory reaction to the impairment of CMA by wild-type UBQLN2. However, ALS-associated mutant UBQLN2 failed to show this compensation, exacerbating the impairment of CMA by mutant UBQLN2. We further demonstrated that ALS-associated mutant forms of UBQLN2 also impair MA, but wild-type UBQLN2 does not. These results support the view that ALS-associated mutant forms of UBQLN2 impair both CMA and MA which may contribute to the neurodegeneration observed in patients with UBQLN2-mediated ALS.}, } @article {pmid37257710, year = {2023}, author = {Kim, S and Yang, M and Ku, B and Cha, E and Seo, W and Son, I and Kang, H and Kim, D and Song, B and Yang, CS and Kim, S}, title = {Efficacy of mecasin for treatment of amyotrophic lateral sclerosis: A phase IIa multicenter randomized double-blinded placebo-controlled trial.}, journal = {Journal of ethnopharmacology}, volume = {315}, number = {}, pages = {116670}, doi = {10.1016/j.jep.2023.116670}, pmid = {37257710}, issn = {1872-7573}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy ; Double-Blind Method ; Vital Capacity ; Disease Progression ; Pain ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a lethal neurodegenerative disorder characterized by progressive paralysis of voluntary muscles. Mecasin, the extract of modified jakyakgamchobuja-tang-a herbal preparation comprising of Radix Paeoniae Alba, Radix Glycyrrhizae, Radix Aconiti Lateralis Preparata, Radix Salviae Miltiorrhizae, Rhizoma Gastrodiae, Radix Polygalae, Curcuma Root, Fructus Chaenomelis, and Rhizoma Atractylodis Japonicae-shows neuroprotective and anti-neuroinflammatory effects and alleviates the symptoms in patients with ALS.

AIM OF THE STUDY: This trial aimed to evaluate the efficacy and safety of mecasin in these patients.

MATERIAL AND METHODS: Patients were randomized to receive mecasin 1.6 g daily, mecasin 2.4 g daily, or placebo for 12 weeks. The primary endpoint was the Korean version of ALS Functional Rating Scale-Revised (K-ALSFRS-R) score. The secondary endpoints were muscular atrophy measurements, pulmonary function test results, creatine kinase levels, body weight, safety, and scores of the Medical Research Council (MRC) scale for muscle strength; Visual Analog Scale for pain (VAS pain); Hamilton Rating Scale for Depression; and Fatigue Severity Scale.

RESULTS: Among the 30 patients randomized, 24 completed the follow-up. Significant between-group differences were detected in the primary endpoint using the omnibus F-test. The changes in the K-ALSFRS-R score between 12 weeks and baseline were -0·25, -1·32, and -2·78 in the mecasin 1.6 g, mecasin 2.4 g, and placebo groups, respectively. The difference in the K-ALSFRS-R score between the mecasin 1.6 g and placebo groups was 2·53 points (95% confidence interval [CI]: 0·61-4·45), and that between the 2.4 g and placebo groups was 1·46 points (95% CI: 0·48-3·40). However, no significant differences were detected in the secondary endpoints (MRC: dyspnea, p = 0·139; VAS pain, p = 0·916; forced vital capacity, p = 0·373). The incidence of adverse events was similar and low in all groups.

CONCLUSIONS: Mecasin may retard symptomatic progression without major adverse effects. A phase IIb study to evaluate its long-term effects in ALS is ongoing.}, } @article {pmid37257665, year = {2023}, author = {Lazo, PA and Morejón-García, P}, title = {VRK1 variants at the cross road of Cajal body neuropathogenic mechanisms in distal neuropathies and motor neuron diseases.}, journal = {Neurobiology of disease}, volume = {183}, number = {}, pages = {106172}, doi = {10.1016/j.nbd.2023.106172}, pmid = {37257665}, issn = {1095-953X}, mesh = {Humans ; Coiled Bodies/metabolism ; Syndrome ; Mutation ; *Motor Neuron Disease/metabolism ; Intracellular Signaling Peptides and Proteins/genetics ; *Charcot-Marie-Tooth Disease/genetics ; }, abstract = {Distal hereditary neuropathies and neuro motor diseases are complex neurological phenotypes associated with pathogenic variants in a large number of genes, but in some the origin is unknown. Recently, rare pathogenic variants of the human VRK1 gene have been associated with these neurological phenotypes. All VRK1 pathogenic variants are recessive, and their clinical presentation occurs in either homozygous or compound heterozygous patients. The pathogenic VRK1 gene pathogenic variants are located in three clusters within the protein sequence. The main, and initial, shared clinical phenotype among VRK1 pathogenic variants is a distal progressive loss of motor and/or sensory function, which includes diseases such as spinal muscular atrophy, Charcot-Marie-Tooth, amyotrophic lateral sclerosis and hereditary spastic paraplegia. In most cases, symptoms start early in infancy, or in utero, and are slowly progressive. Additional neurological symptoms vary among non-related patients, probably because of their different VRK1 variants and their genetic background. The underlying common pathogenic mechanism, by its functional impairment, is a likely consequence of the roles that the VRK1 protein plays in the regulation on the stability and assembly of Cajal bodies, which affect RNA maturation and processing, neuronal migration of RNPs along axons, and DNA-damage responses. Alterations of these processes are associated with several neuro sensory or motor syndromes. The clinical heterogeneity of the neurological phenotypes associated with VRK1 is a likely consequence of the protein complexes in which VRK1 is integrated, which include several proteins known to be associated with Cajal bodies and DNA damage responses. Several hereditary distal neurological diseases are a consequence of pathogenic variants in genes that alter these cellular functions. We conclude that VRK1-related distal hereditary neuropathies and motor neuron diseases represent a novel subgroup of Cajal body related neurological syndromes.}, } @article {pmid37257467, year = {2023}, author = {Fidelix, EC and Santana, GC and Barros, DMDS and Dourado Junior, MET}, title = {Telehealth for amyotrophic lateral sclerosis in a multidisciplinary service in a Brazilian reference center.}, journal = {Arquivos de neuro-psiquiatria}, volume = {81}, number = {5}, pages = {469-474}, pmid = {37257467}, issn = {1678-4227}, mesh = {Humans ; Male ; Female ; *Amyotrophic Lateral Sclerosis/therapy ; Brazil ; Retrospective Studies ; *COVID-19 ; *Telemedicine ; }, abstract = {BACKGROUND: Telehealth has been used in the treatment of different diseases, and it has been shown to provide benefits for patients with amyotrophic lateral sclerosis (ALS). Due to the social distancing measures put into effect during the coronavirus disease 2019 (COVID-19) pandemic, there was an urgent need for telehealth to ensure the provision of healthcare.

OBJECTIVE: To evaluate the feasibility of telehealth for the provision of multidisciplinary ALS care, and to assess its acceptability among patients and caregivers.

METHODS: We conducted a retrospective cohort study in which multidisciplinary evaluations were performed using the Teleconsulta platform. The patients included had ALS and at least one in-person clinical evaluation. The patients and the caregivers answered satisfaction questionnaires.

RESULTS: The sample was composed of 46 patients, 32 male and 14 female subjects. The average distance from their residences to the reference services was of 115 km. Respiratory adjustment was the most addressed topic.

CONCLUSION: The strategy is viable and well accepted in terms of satisfaction. It was even more positive for patients in advanced stages of the disease or for those living far from the referral center.}, } @article {pmid37256664, year = {2023}, author = {Castillo Padrós, MR and Pastor, N and Altarriba Paracolls, J and Mosquera Peña, M and Pergolizzi, D and Salvador Vergès, À}, title = {A Smart System for Remote Monitoring of Patients in Palliative Care (HumanITcare Platform): Mixed Methods Study.}, journal = {JMIR formative research}, volume = {7}, number = {}, pages = {e45654}, pmid = {37256664}, issn = {2561-326X}, abstract = {BACKGROUND: Due to the complexities of advanced illnesses and their treatments, it can be difficult for patients in palliative care to maintain their quality of life. Telemedicine interventions in chronic disease management engage patients in their care, provide continuous follow-up by their health care providers, identify symptoms earlier, and allow a quick response to illness-related decline.

OBJECTIVE: We aimed to detail and reflect on the design of an app and evaluate its feasibility to monitor the clinical situation of patients with advanced illnesses.

METHODS: This study used a mixed methods design using qualitative methods to inform app development and design and quantitative methods for data collection and analysis of patient evaluations. Palliative care units in 2 Spanish university hospitals (Nuestra Señora de la Candelaria in Santa Cruz de Tenerife and University Hospital Complex of Ferrol in A Coruña) carried out a literature review, designed the study protocol, and obtained approval from the Ethics Committee from June to December 2020. In addition, focus group meetings were held, and the design and technical development of the app were elaborated on and subsequently presented in the participating palliative care units. From January to March 2021, the app was made public on the App Store and Play Store, and a pilot study with patients was carried out in April to September 2021.

RESULTS: Six focus group meetings were held that included doctors, nurses, app developers, technology consultants, and sponsors. In addition, the technology consultants presented their results 3 times in the participating palliative care units to obtain feedback. After the app's final design, it was possible to publish it on the usual servers and begin its evaluation in patients (n=60, median age 72 years). Sixty percent (n=36) of the participants were women and 40% (n=24) were men. The most prevalent advanced pathology was cancer (n=46, 76%), followed by other diseases (n=7, 12%) and amyotrophic lateral sclerosis (n=5, 8%). Seventy percent (n=42) of the patients were already in follow-up prior to the start of the study, while 30% (n=18) were included at the start of their follow-up. The information in the app was collected and entered by relatives or caregivers in 60% (n=36) of the cases. The median follow-up was 52 (IQR 14-104) days. In all, 69% (n=41) had a follow-up >30 days (10 were deceased and 9 were missing data). The use of the different sections of the app ranged from 37% (n=22) for the glycemic record to 90% (n=54) for the constipation scale). Patients and caregivers were delighted with its ease of use and usefulness.

CONCLUSIONS: Incorporating an intelligent remote patient monitoring system in clinical practice for patients in palliative care can improve access to health services and provide more information to professionals.}, } @article {pmid37256332, year = {2023}, author = {Tayebi, H and Azadnajafabad, S and Maroufi, SF and Pour-Rashidi, A and Khorasanizadeh, M and Faramarzi, S and Slavin, KV}, title = {Applications of brain-computer interfaces in neurodegenerative diseases.}, journal = {Neurosurgical review}, volume = {46}, number = {1}, pages = {131}, pmid = {37256332}, issn = {1437-2320}, mesh = {Humans ; *Brain-Computer Interfaces ; Electroencephalography/methods ; *Neurodegenerative Diseases/therapy ; Brain ; Central Nervous System ; }, abstract = {Brain-computer interfaces (BCIs) provide the central nervous system with channels of direct communication to the outside world, without having to go through the peripheral nervous system. Neurodegenerative diseases (NDs) are notoriously incurable and burdensome medical conditions that will result in progressive deterioration of the nervous system. The applications of BCIs in NDs have been studied for decades now through different approaches, resulting in a considerable amount of literature in all related areas. In this study, we begin by introducing BCIs and proceed by explaining the principles of BCI-based neurorehabilitation. Then, we go through four specific types of NDs, including amyotrophic lateral sclerosis, Parkinson's disease, Alzheimer's disease, and spinal muscular atrophy, and review some of the applications of BCIs in the neural rehabilitation of these diseases. We conclude with a discussion of the characteristics, challenges, and future possibilities of research in the field. Going through the uses of BCIs in NDs, we can see that approaches and strategies employed to tackle the wide range of limitations caused by NDs are numerous and diverse. Furthermore, NDs can fall under different categories based on the target area of neurodegeneration and thus require different methods of BCI-based rehabilitation. In recent years, neurotechnology companies have substantially invested in research on BCIs, focusing on commercializing BCIs and bringing BCI-based technologies from bench to bedside. This can mean the beginning of a new era for BCI-based neurorehabilitation, with an anticipated spike in interest among researchers, practitioners, engineers, and entrepreneurs alike.}, } @article {pmid37255643, year = {2023}, author = {Saucedo, S and Katsuura, Y}, title = {Preventing Unnecessary Surgery in Patients Presenting for Orthopedic Spine Surgery: Literature Review and Case Series.}, journal = {Journal of orthopaedic case reports}, volume = {13}, number = {5}, pages = {76-81}, pmid = {37255643}, issn = {2250-0685}, abstract = {INTRODUCTION: Almost 40% of patients who have been diagnosed with amyotrophic lateral sclerosis (ALS) may have been misdiagnosed. Some of these patients may have undergone surgical procedures to address symptoms that could have actually be early indications of ALS.Up to 40% of patients diagnosed with amyotrophic lateral sclerosis (ALS) have received an incorrect diagnosis, a number undergo surgical treatment for signs and symptoms that can be attributed to early manifestations of ALS. Initial presentation of ALS is elusive and is often mistaken for other disorders originating from the cervical spine such as cervical radiculopathy or myelopathy. Such incorrect diagnoses often display symptoms that fall within the scope of an orthopedic spine surgeon, who can remedy said diagnoses. Given that a diagnosis of ALS is grave, it is crucial to establish a definitive diagnosis quickly, without unnecessary surgery. The objective of this series is to highlight patients who were referred by other physicians for spine surgery to remedy potential side effects of cervical myelopathy but were ultimately diagnosed with ALS.

CASE REPORT: Case 1: A 46-year-old Caucasian woman with carpal tunnel syndrome and cervical intervertebral disc degeneration. Case 2: A 77-year-old African American man with a history of arthritis, GERD, a herniated disc, claw hand, hypertension, prostate disease, and general weakness. Case 3: A 74-year-old Caucasian woman with a background history of hypertension, dyslipidemia, hypothyroidism, osteopenia, and foot drop.

CONCLUSION: In orthopedic spine surgery, ALS could be an easily misdiagnosed disease, which can be mistaken for cervical spondylosis, cervical radiculopathy, cervical myelopathy, lumbar radiculopathy, and lumbar myelopathy; it is of note to be aware of how ALS may initially present. It is imperative for the orthopedic spine surgeon to consider ALS with patients presenting with progressive unilateral/bilateral upper extremity weakness.}, } @article {pmid37254833, year = {2023}, author = {White, S and O'Cathain, A and Halliday, V and Croot, L and McDermott, CJ}, title = {Factors influencing decisions people with motor neuron disease make about gastrostomy placement and ventilation: A qualitative evidence synthesis.}, journal = {Health expectations : an international journal of public participation in health care and health policy}, volume = {26}, number = {4}, pages = {1418-1435}, pmid = {37254833}, issn = {1369-7625}, support = {NIHR301592//National Institute for Health and Care Research/ ; }, mesh = {Humans ; *Gastrostomy/psychology ; Quality of Life ; *Motor Neuron Disease/therapy/complications/psychology ; Health Personnel ; Caregivers/psychology ; }, abstract = {BACKGROUND: People with motor neuron disease (pwMND) are routinely offered gastrostomy feeding tube placement and (non-invasive and invasive) ventilation to manage the functional decline associated with the disease. This study aimed to synthesise the findings from the qualitative literature to understand how individual, clinical team and organisational factors influence pwMND decisions about these interventions.

METHODS: The study design was guided by the enhancing transparency in reporting the synthesis of qualitative research (ENTREC) statement. The search of five bibliography databases and an extensive supplementary search strategy identified 27 papers that included qualitative accounts of pwMND, caregivers and healthcare professionals' (HCPs) experiences of making decisions about gastrostomy and ventilation. The findings from each study were included in a thematic synthesis.

FINDINGS: Making decisions about interventions is an emotional rather than simply a functional issue for pwMND. The interventions can signal an end to normality, and increasing dependence, where pwMND consider the balance between quality of life and extending survival. Interactions with multiple HCPs and caregivers can influence the process of decision-making and the decisions made. These interactions contribute to the autonomy pwMND are able to exert during decision-making. HCPs can both promote and threaten pwMND perceived agency over decisions through how they approach discussions about these interventions. Though there is uncertainty over the timing of interventions, pwMND who agree to interventions report reaching a tipping point where they accept the need for change.

CONCLUSION: Discussion of gastrostomy and ventilation options generate an emotional response in pwMND. Decisions are the consequence of interactions with multiple external agents, including HCPs treading a complex ethical path when trying to improve health outcomes while respecting pwMND right to autonomy. Future decision support interventions that address the emotional response and seek to support autonomy have the potential to enable pwMND to make informed and timely decisions about gastrostomy placement and ventilation.

The lead author collaborated with several patient and participant involvement (PPI) groups with regards to the conceptualisation and design of this project. Decisions that have been influenced by discussions with multiple PPI panels include widening the scope of decisions about ventilation in addition to gastrostomy placement and the perceptions of all stakeholders involved (i.e., pwMND, caregivers and HCPs).}, } @article {pmid37254449, year = {2023}, author = {Shefner, JM and Al-Chalabi, A and Andrews, JA and Chio, A and De Carvalho, M and Cockroft, BM and Corcia, P and Couratier, P and Cudkowicz, ME and Genge, A and Hardiman, O and Heiman-Patterson, T and Henderson, RD and Ingre, C and Jackson, CE and Johnston, W and Lechtzin, N and Ludolph, A and Maragakis, NJ and Miller, TM and Mora Pardina, JS and Petri, S and Simmons, Z and Van Den Berg, LH and Zinman, L and Kupfer, S and Malik, FI and Meng, L and Simkins, TJ and Wei, J and Wolff, AA and Rudnicki, SA}, title = {COURAGE-ALS: a randomized, double-blind phase 3 study designed to improve participant experience and increase the probability of success.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {24}, number = {5-6}, pages = {523-534}, doi = {10.1080/21678421.2023.2216223}, pmid = {37254449}, issn = {2167-9223}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/drug therapy ; *Courage ; Double-Blind Method ; Probability ; Disease Progression ; }, abstract = {Objective: To determine the target population and optimize the study design of the phase 3 clinical trial evaluating reldesemtiv in participants with amyotrophic lateral sclerosis (ALS).Methods: We evaluated the phase 2 study of reldesemtiv, FORTITUDE-ALS, to inform eligibility criteria and design features that would increase trial efficiency and reduce participant burden of the phase 3 trial.Results: In FORTITUDE-ALS, the effect of reldesemtiv was particularly evident among participants in the intermediate- and fast-progressing tertiles for pre-study disease progression. These participants most often had symptom onset ≤24 months and an ALS Functional Rating Scale-Revised (ALSFRS-R) total score ≤44 at baseline. Compared with the overall FORTITUDE-ALS population, the subgroup meeting these criteria declined by fewer ALSFRS-R points at 12 weeks (difference of least-squares mean [SE] versus placebo 1.84 [0.49] and 0.87 [0.35] for the overall population). These inclusion criteria will be used for the phase 3 clinical trial, COURAGE-ALS, in which the primary outcome is the change in ALSFRS-R total score at week 24. We also measure durable medical equipment use and evaluate strength in muscles expected to change rapidly. To reduce participant burden, study visits are often remote, and strength evaluation is simplified to reduce time and effort.Conclusions: In COURAGE-ALS, the phase 3 clinical trial to evaluate reldesemtiv, the sensitivity of detecting a potential treatment effect may be increased by defining eligibility criteria that limit the proportion of participants who have slower disease progression. Implementing remote visits and simplifying strength measurements will reduce both site and participant burden.ClinicalTrials.gov identifiers: NCT03160898 (FORTITUDE-ALS) and NCT04944784 (COURAGE-ALS).}, } @article {pmid37253318, year = {2023}, author = {Liu, W and Ma, R and Sun, C and Xu, Y and Liu, Y and Hu, J and Ma, Y and Wang, D and Wen, D and Yu, Y}, title = {Implications from proteomic studies investigating circadian rhythm disorder-regulated neurodegenerative disease pathology.}, journal = {Sleep medicine reviews}, volume = {70}, number = {}, pages = {101789}, doi = {10.1016/j.smrv.2023.101789}, pmid = {37253318}, issn = {1532-2955}, mesh = {Humans ; *Neurodegenerative Diseases ; Proteomics ; *Parkinson Disease/metabolism ; *Alzheimer Disease ; *Chronobiology Disorders ; Circadian Rhythm/genetics ; }, abstract = {Neurodegenerative diseases (NDs) affect 15% of the world's population and are becoming an increasingly common cause of morbidity and mortality worldwide. Circadian rhythm disorders (CRDs) have been reported to be involved in the pathogenic regulation of various neurologic diseases, including Alzheimer's disease, Parkinson's disease, Huntington's disease, multiple sclerosis and amyotrophic lateral sclerosis. Proteomic technology is helpful to explore treatment targets for CRDs in patients with NDs. Here, we review the key differentially expressed (DE) proteins identified in previous proteomic studies investigating NDs, CRDs and associated models and the related pathways identified by enrichment analysis. Furthermore, we summarize the advantages and disadvantages of the above studies and propose new proteomic technologies for the precise study of circadian disorder-mediated regulation of ND pathology. This review provides a theoretical and technical reference for the precise study of circadian disorder-mediated regulation of ND pathology.}, } @article {pmid37252342, year = {2023}, author = {Wajnberg, G and Allain, EP and Roy, JW and Srivastava, S and Saucier, D and Morin, P and Marrero, A and O'Connell, C and Ghosh, A and Lewis, SM and Ouellette, RJ and Crapoulet, N}, title = {Application of annotation-agnostic RNA sequencing data analysis tools for biomarker discovery in liquid biopsy.}, journal = {Frontiers in bioinformatics}, volume = {3}, number = {}, pages = {1127661}, pmid = {37252342}, issn = {2673-7647}, abstract = {RNA sequencing analysis is an important field in the study of extracellular vesicles (EVs), as these particles contain a variety of RNA species that may have diagnostic, prognostic and predictive value. Many of the bioinformatics tools currently used to analyze EV cargo rely on third-party annotations. Recently, analysis of unannotated expressed RNAs has become of interest, since these may provide complementary information to traditional annotated biomarkers or may help refine biological signatures used in machine learning by including unknown regions. Here we perform a comparative analysis of annotation-free and classical read-summarization tools for the analysis of RNA sequencing data generated for EVs isolated from persons with amyotrophic lateral sclerosis (ALS) and healthy donors. Differential expression analysis and digital-droplet PCR validation of unannotated RNAs also confirmed their existence and demonstrates the usefulness of including such potential biomarkers in transcriptome analysis. We show that find-then-annotate methods perform similarly to standard tools for the analysis of known features, and can also identify unannotated expressed RNAs, two of which were validated as overexpressed in ALS samples. We demonstrate that these tools can therefore be used for a stand-alone analysis or easily integrated into current workflows and may be useful for re-analysis as annotations can be integrated post hoc.}, } @article {pmid37252191, year = {2023}, author = {Maruyama, T and Tanabe, S and Uyeda, A and Suzuki, T and Muramatsu, R}, title = {Free fatty acids support oligodendrocyte survival in a mouse model of amyotrophic lateral sclerosis.}, journal = {Frontiers in cellular neuroscience}, volume = {17}, number = {}, pages = {1081190}, pmid = {37252191}, issn = {1662-5102}, abstract = {INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the white matter degeneration. Although changes in blood lipids are involved in the pathogenesis of neurological diseases, the pathological role of blood lipids in ALS remains unclear.

METHODS AND RESULTS: We performed lipidome analysis on the plasma of ALS model mice, mutant superoxide dismutase 1 (SOD1[G93A]) mice, and found that the concentration of free fatty acids (FFAs), including oleic acid (OA) and linoleic acid (LA), decreased prior to disease onset. An in vitro study revealed that OA and LA directly inhibited glutamate-induced oligodendrocytes cell death via free fatty acid receptor 1 (FFAR1). A cocktail containing OA/LA suppressed oligodendrocyte cell death in the spinal cord of SOD1[G93A] mice.

DISCUSSION: These results suggested that the reduction of FFAs in the plasma is a pathogenic biomarker for ALS in the early stages, and supplying a deficiency in FFAs is a potential therapeutic approach for ALS by preventing oligodendrocyte cell death.}, } @article {pmid37251807, year = {2023}, author = {Allen, SP and Al Sultan, A and Kabucho Kibirige, E and Tonkiss, E and Hamer, KJ and Castelli, LM and Lin, YH and Roscoe, S and Stefanidis, N and Mead, RJ and Highley, JR and Cooper-Knock, J and Hautbergue, GM and Heath, PR and Kirby, J and Shaw, PJ}, title = {A Y374X TDP43 truncation leads to an altered metabolic profile in amyotrophic lateral sclerosis fibroblasts driven by pyruvate and TCA cycle intermediate alterations.}, journal = {Frontiers in aging neuroscience}, volume = {15}, number = {}, pages = {1151848}, pmid = {37251807}, issn = {1663-4365}, support = {/WT_/Wellcome Trust/United Kingdom ; ALLEN/OCT15/956-799/MNDA_/Motor Neurone Disease Association/United Kingdom ; }, abstract = {A p.Y374X truncation in TARDBP was recently shown to reduce expression of TDP43 in fibroblasts isolated from ALS cases. In this follow up study focused on assessing the downstream phenotypic consequences of loss of TDP43 in the context of the truncation, we have shown a striking effect on the fibroblast metabolic profile. Phenotypic metabolic screening uncovered a distinct metabolic profile in TDP43-Y374X fibroblasts compared to controls, which was driven by alterations in key metabolic checkpoint intermediates including pyruvate, alpha-ketoglutarate and succinate. These metabolic alterations were confirmed using transcriptomics and bioenergetic flux analysis. These data suggest that TDP43 truncation directly compromises glycolytic and mitochondrial function, identifying potential therapeutic targets for mitigating the effects of TDP43-Y374X truncation.}, } @article {pmid37250416, year = {2023}, author = {Wang, H and Guan, L and Deng, M}, title = {Recent progress of the genetics of amyotrophic lateral sclerosis and challenges of gene therapy.}, journal = {Frontiers in neuroscience}, volume = {17}, number = {}, pages = {1170996}, pmid = {37250416}, issn = {1662-4548}, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by the degeneration of motor neurons in the brain and spinal cord. The causes of ALS are not fully understood. About 10% of ALS cases were associated with genetic factors. Since the discovery of the first familial ALS pathogenic gene SOD1 in 1993 and with the technology advancement, now over 40 ALS genes have been found. Recent studies have identified ALS related genes including ANXA11, ARPP21, CAV1, C21ORF2, CCNF, DNAJC7, GLT8D1, KIF5A, NEK1, SPTLC1, TIA1, and WDR7. These genetic discoveries contribute to a better understanding of ALS and show the potential to aid the development of better ALS treatments. Besides, several genes appear to be associated with other neurological disorders, such as CCNF and ANXA11 linked to FTD. With the deepening understanding of the classic ALS genes, rapid progress has been made in gene therapies. In this review, we summarize the latest progress on classical ALS genes and clinical trials for these gene therapies, as well as recent findings on newly discovered ALS genes.}, } @article {pmid37250330, year = {2023}, author = {Pang, W and Hu, F}, title = {C9ORF72 suppresses JAK-STAT mediated inflammation.}, journal = {iScience}, volume = {26}, number = {5}, pages = {106579}, pmid = {37250330}, issn = {2589-0042}, abstract = {Hexanucleotide repeat expansion in the gene C9ORF72 is a leading cause of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). C9ORF72 deficiency leads to severe inflammatory phenotypes in mice, but exactly how C9ORF72 regulates inflammation remains to be fully elucidated. Here, we report that loss of C9ORF72 leads to the hyperactivation of the JAK-STAT pathway and an increase in the protein levels of STING, a transmembrane adaptor protein involved in immune signaling in response to cytosolic DNA. Treatment with a JAK inhibitor rescues the enhanced inflammatory phenotypes caused by C9ORF72 deficiency in cell culture and mice. Furthermore, we showed that the ablation of C9ORF72 results in compromised lysosome integrity, which could contribute to the activation of the JAK/STAT-dependent inflammatory responses. In summary, our study identifies a mechanism by which C9ORF72 regulates inflammation, which might facilitate therapeutic development for ALS/FTLD with C9ORF72 mutations.}, } @article {pmid37250128, year = {2023}, author = {Mazzaro, A and Vita, V and Ronfini, M and Casola, I and Klein, A and Dobrowolny, G and Sorarù, G and Musarò, A and Mongillo, M and Zaglia, T}, title = {Sympathetic neuropathology is revealed in muscles affected by amyotrophic lateral sclerosis.}, journal = {Frontiers in physiology}, volume = {14}, number = {}, pages = {1165811}, pmid = {37250128}, issn = {1664-042X}, abstract = {Rationale: The anatomical substrate of skeletal muscle autonomic innervation has remained underappreciated since it was described many decades ago. As such, the structural and functional features of muscle sympathetic innervation are largely undetermined in both physiology and pathology, mainly due to methodological limitations in the histopathological analysis of small neuronal fibers in tissue samples. Amyotrophic lateral sclerosis (ALS) is a fatal neuromuscular disease which mainly targets motor neurons, and despite autonomic symptoms occurring in a significant fraction of patients, peripheral sympathetic neurons (SNs) are generally considered unaffected and, as such, poorly studied. Purpose: In this research, we compared sympathetic innervation of normal and ALS muscles, through structural analysis of the sympathetic network in human and murine tissue samples. Methods and Results: We first refined tissue processing to circumvent methodological limitations interfering with the detection of muscle sympathetic innervation. The optimized "Neuro Detection Protocol" (NDP) was validated in human muscle biopsies, demonstrating that SNs innervate, at high density, both blood vessels and skeletal myofibers, independent of the fiber metabolic type. Subsequently, NDP was exploited to analyze sympathetic innervation in muscles of SOD1[G93A] mice, a preclinical ALS model. Our data show that ALS murine muscles display SN denervation, which has already initiated at the early disease stage and worsened during aging. SN degeneration was also observed in muscles of MLC/SOD1[G93A] mice, with muscle specific expression of the SOD1[G93A] mutant gene. Notably, similar alterations in SNs were observed in muscle biopsies from an ALS patient, carrying the SOD1[G93A] mutation. Conclusion: We set up a protocol for the analysis of murine and, more importantly, human muscle sympathetic innervation. Our results indicate that SNs are additional cell types compromised in ALS and suggest that dysfunctional SOD1[G93A] muscles affect their sympathetic innervation.}, } @article {pmid37249795, year = {2023}, author = {Patel, RB and Bajpai, AK and Thirumurugan, K}, title = {Differential Expression of MicroRNAs and Predicted Drug Target in Amyotrophic Lateral Sclerosis.}, journal = {Journal of molecular neuroscience : MN}, volume = {73}, number = {6}, pages = {375-390}, pmid = {37249795}, issn = {1559-1166}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy/genetics/diagnosis ; *Neurodegenerative Diseases ; *Curcumin ; Molecular Docking Simulation ; *MicroRNAs/genetics/metabolism ; Gene Expression Profiling ; }, abstract = {ALS (Amyotrophic Lateral Sclerosis) is a rare type of neurodegenerative disease. It shows progressive degradation of motor neurons in the brain and spinal cord. At present, there is no treatment available that can completely cure ALS. The available treatments can only increase a patient's life span by a few months. Recently, microRNAs (miRNAs), a sub-class of small non-coding RNAs have been shown to play an essential role in the diagnosis, prognosis, and therapy of ALS. Our study focuses on analyzing differential miRNA profiles and predicting drug targets in ALS using bioinformatics and computational approach. The study identifies eight highly differentially expressed miRNAs in ALS patients, four of which are novel. We identified 42 hub genes for these eight highly expressed miRNAs with Amyloid Precursor Protein (APP) as a candidate gene among them for highly expressed down-regulated miRNA, hsa-miR-455-3p using protein-protein interaction network and Cytoscape analysis. A novel association has been found between hsa-miR-455-3p/APP/serotonergic pathway using KEGG pathway analysis. Also, molecular docking studies have revealed curcumin as a potential drug target that may be used for the treatment of ALS. Thus, the present study has identified four novel miRNA biomarkers: hsa-miR-3613-5p, hsa-miR-24, hsa-miR-3064-5p, and hsa-miR-4455. There is a formation of a novel axis, hsa-miR-455-3p/APP/serotonergic pathway, and curcumin is predicted as a potential drug target for ALS.}, } @article {pmid37249667, year = {2023}, author = {Nourelden, AZ and Kamal, I and Hagrass, AI and Tawfik, AG and Elhady, MM and Fathallah, AH and Eshag, MME and Zaazouee, MS}, title = {Safety and efficacy of edaravone in patients with amyotrophic lateral sclerosis: a systematic review and meta-analysis.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {44}, number = {10}, pages = {3429-3442}, pmid = {37249667}, issn = {1590-3478}, mesh = {United States ; Humans ; Edaravone/therapeutic use ; *Amyotrophic Lateral Sclerosis/drug therapy/chemically induced ; Prospective Studies ; Quality of Life ; Severity of Illness Index ; }, abstract = {AIM: The study aims to increase understanding of edaravone's efficacy and safety as an amyotrophic lateral sclerosis (ALS) treatment and provide significant insights regarding this field's future research.

METHODS: We conducted a comprehensive search of the Embase, PubMed, Cochrane Library, Web of Science, and Scopus databases for randomized controlled trials and observational studies up until September 2022. We evaluated the studies' quality using the Cochrane risk of bias tool and the National Institutes of Health tool.

RESULTS: We included 11 studies with 2845 ALS patients. We found that edaravone improved the survival rate at 18, 24, and 30 months (risk ratio (RR) = 1.03, 95% confidence interval (CI) [1.02 to 1.24], P = 0.02), (RR = 1.22, 95% CI [1.06 to 1.41], P = 0.007), and (RR = 1.17, 95% CI [1.01 to 1.34], P = 0.03), respectively. However, the administration of edaravone did not result in any significant difference in adverse effects or efficacy outcomes between the two groups, as indicated by a P value greater than 0.05.

CONCLUSION: Edaravone improves survival rates of ALS patients at 18, 24, and 30 months with no adverse effects. However, edaravone does not affect functional outcomes. In order to ensure the validity of our findings and assess the results in accordance with the disease stage, it is essential to carry out additional prospective, rigorous, and high-quality clinical trials. The current study offers preliminary indications regarding the effectiveness and safety of edaravone. However, further comprehensive research is required to establish the generalizability and sustainability of the findings.}, } @article {pmid37248728, year = {2023}, author = {Young, HM and Kilaberia, TR and Whitney, R and Link, BM and Bell, JF and Tonkikh, O and Famula, J and Oskarsson, B}, title = {Needs of persons living with ALS at home and their family caregivers: A scoping review.}, journal = {Muscle & nerve}, volume = {68}, number = {3}, pages = {240-249}, doi = {10.1002/mus.27849}, pmid = {37248728}, issn = {1097-4598}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy/psychology ; Caregivers/psychology ; Cross-Sectional Studies ; *Home Care Services ; Emotions ; }, abstract = {INTRODUCTION/AIMS: Most persons with amyotrophic lateral sclerosis (ALS) live at home with support of family caregivers, with escalating complexity of care over the trajectory of the disease requiring resources and support to mitigate negative physical, social, and emotional outcomes.

METHODS: This scoping review identifies the home health/home care needs of persons with ALS and their caregivers as a basis for creating a home health medical standard. We used the PRISMA Extension for Scoping Reviews (PRISMA-ScR) to examine studies describing home care needs published between 2011 and 2021.

RESULTS: Our search yielded 481 articles, of which 44 were included with a total of 3592 (9-273) participants. Most studies used a cross-sectional design and 20 (45%) were rated as high quality. We grouped the needs identified as emotional/psychological, assistive devices and technology, information and education, and human resources and professional services. Most studies demonstrated persistent unmet needs and that available interventions were helpful while needs generally were not met proactively, despite the predictable trajectory.

DISCUSSION: This review describes biopsychosocial and equipment interventions over the trajectory of ALS with implications for anticipatory planning by clinicians, as well as policy for coverage of necessary services and supports. Interdisciplinary expert teams could develop consensus around needs across the trajectory and recommended services and supports. To make knowledge more accessible, encourage availability of services, and clarify the need for coverage of services, we aim to develop an expert consensus-based ALS home health medical standard guidance document in collaboration with the American Association of Neuromuscular and Electrodiagnostic Medicine.}, } @article {pmid37248338, year = {2023}, author = {Kumar, ST and Nazarov, S and Porta, S and Maharjan, N and Cendrowska, U and Kabani, M and Finamore, F and Xu, Y and Lee, VM and Lashuel, HA}, title = {Seeding the aggregation of TDP-43 requires post-fibrillization proteolytic cleavage.}, journal = {Nature neuroscience}, volume = {26}, number = {6}, pages = {983-996}, pmid = {37248338}, issn = {1546-1726}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism ; *TDP-43 Proteinopathies/pathology ; *Frontotemporal Lobar Degeneration/metabolism ; *Frontotemporal Dementia ; DNA-Binding Proteins/genetics/metabolism ; }, abstract = {Despite the strong evidence linking the transactive response DNA-binding protein 43 (TDP-43) aggregation to the pathogenesis of frontotemporal lobar degeneration with TDP-43, amyotrophic lateral sclerosis and several neurodegenerative diseases, our knowledge of the sequence and structural determinants of its aggregation and neurotoxicity remains incomplete. Herein, we present a new method for producing recombinant full-length TDP-43 filaments that exhibit sequence and morphological features similar to those of brain-derived TDP-43 filaments. We show that TDP-43 filaments contain a β-sheet-rich helical amyloid core that is fully buried by the flanking structured domains of the protein. We demonstrate that the proteolytic cleavage of TDP-43 filaments and exposure of this amyloid core are necessary for propagating TDP-43 pathology and enhancing the seeding of brain-derived TDP-43 aggregates. Only TDP-43 filaments with exposed amyloid core efficiently seeded the aggregation of endogenous TDP-43 in cells. These findings suggest that inhibiting the enzymes mediating cleavage of TDP-43 aggregates represents a viable disease-modifying strategy to slow the progression of amyotrophic lateral sclerosis and other TDP-43 proteinopathies.}, } @article {pmid37248019, year = {2023}, author = {Zhang, L and Wang, W and Du, Y and Deng, Y and Bai, T and Ji, M}, title = {Multiple resistance of Echinochloa phyllopogon to synthetic auxin, ALS-, and ACCase-inhibiting herbicides in Northeast China.}, journal = {Pesticide biochemistry and physiology}, volume = {193}, number = {}, pages = {105450}, doi = {10.1016/j.pestbp.2023.105450}, pmid = {37248019}, issn = {1095-9939}, mesh = {Herbicide Resistance/genetics ; *Echinochloa/genetics ; Indoleacetic Acids ; *Herbicides/pharmacology ; Acetyl-CoA Carboxylase/genetics ; }, abstract = {Echinochloa phyllopogon is a self-pollinating allotetraploid weed and a serious threat to global rice production. One sensitive and three multiple-resistant populations collected from two provinces of Northeast China were used to analyze the mechanism of multiple resistance of E. phyllopogon to penoxsulam, metamifop, and quinclorac. Compared with the sensitive population LN12, LN1 showed higher resistance to these three herbicides; LN24 showed medium resistance to penoxsulam and metamifop and higher resistance to quinclorac (274-fold); HLJ4 showed low resistance to penoxsulam and high resistance to metamifop and quinclorac. Target sequence analysis showed no mutations in acetolactate synthase or acetyl-CoA carboxylase genes. In-vitro enzyme activity analysis showed that the activity of the target enzyme of multiple herbicide-resistant populations was similar to that of the sensitive population. The P450 inhibitor, malathion, noticeably increased the sensitivity of LN1, LN24, and HLJ4 to penoxsulam, LN1 to metamifop, and HLJ4 to quinclorac. Under all four treatments, the GSTs activities of resistant and sensitive populations showed an increasing trend from day 1 to day 5, but the sensitivity and activity of GSTs were higher in the multiple-resistant population than that in the sensitive population LN12. This study identified the development of multiple-resistant E. phyllopogon populations that pose a serious threat to rice production in rice fields in Northeast China, preliminarily confirming that multiple-resistance was likely due to non-target-site resistance mechanisms. These populations of E. phyllopogon are likely to be more difficult to control.}, } @article {pmid37247505, year = {2023}, author = {Moreno, R and Recio, J and Barber, S and Gil, C and Martinez, A}, title = {The emerging role of mixed lineage kinase 3 (MLK3) and its potential as a target for neurodegenerative diseases therapies.}, journal = {European journal of medicinal chemistry}, volume = {257}, number = {}, pages = {115511}, doi = {10.1016/j.ejmech.2023.115511}, pmid = {37247505}, issn = {1768-3254}, mesh = {Humans ; *Neurodegenerative Diseases/drug therapy ; *Parkinson Disease/drug therapy ; MAP Kinase Kinase Kinases ; Cell Death ; Mitogen-Activated Protein Kinase Kinase Kinase 11 ; }, abstract = {Selective and brain-permeable protein kinase inhibitors are in preclinical development for treating neurodegenerative diseases. Among them, MLK3 inhibitors, with a potent neuroprotective biological action have emerged as valuable agents for the treatment of pathologies such as Alzheimer's, Parkinson's disease and amyotrophic lateral sclerosis. In fact, one MLK3 inhibitor, CEP-1347, reached clinical trials for Parkinson's disease. Additionally, another compound called prostetin/12k, a potent and rather selective MLK3 inhibitor has started clinical development for ALS based on its motor neuron protection in both in vitro and in vivo models. In this review, we will focus on the role of MLK3 in neuron-related cell death processes, neurodegenerative diseases, and the potential advantages of targeting this kinase through pharmacological modulation for neuroprotective treatment.}, } @article {pmid37247026, year = {2023}, author = {Becker, W and Behler, A and Vintonyak, O and Kassubek, J}, title = {Patterns of small involuntary fixation saccades (SIFSs) in different neurodegenerative diseases: the role of noise.}, journal = {Experimental brain research}, volume = {241}, number = {7}, pages = {1821-1833}, pmid = {37247026}, issn = {1432-1106}, mesh = {Humans ; Saccades ; *Neurodegenerative Diseases ; *Amyotrophic Lateral Sclerosis ; Fixation, Ocular ; *Supranuclear Palsy, Progressive ; *Ocular Motility Disorders ; }, abstract = {During the attempt to steadily fixate at a single spot, sequences of small involuntary fixation saccades (SIFSs, known also as microsaccades οr intrusions) occur which form spatio-temporal patterns such as square wave jerks (SWJs), a pattern characterised by alternating centrifugal and centripetal movements of similar magnitude. In many neurodegenerative disorders, SIFSs exhibit elevated amplitudes and frequencies. Elevated SIFS amplitudes have been shown to favour the occurrence of SWJs ("SWJ coupling"). We analysed SIFSs in different subject groups comprising both healthy controls (CTR) and patients with amyotrophic lateral sclerosis (ALS) and progressive supranuclear palsy (PSP), i.e. two neurodegenerative diseases with completely different neuropathological basis and different clinical phenotypes. We show that, across these groups, the relations between SIFS amplitude and the relative frequency of SWJ-like patterns and other SIFS characteristics follow a common law. As an explanation, we propose that physiological and technical noise comprises a small, amplitude-independent component that has little effect on large SIFSs, but causes considerable deviations from the intended amplitude and direction of small ones. Therefore, in contrast to large SIFSs, successive small SIFSs have a lower chance to meet the SWJ similarity criteria. In principle, every measurement of SIFSs is affected by an amplitude-independent noise background. Therefore, the dependence of SWJ coupling on SIFS amplitude will probably be encountered in almost any group of subjects. In addition, we find a positive correlation between SIFS amplitude and frequency in ALS, but none in PSP, suggesting that the elevated amplitudes might arise at different sites in the two disorders.}, } @article {pmid37246507, year = {2023}, author = {Pillai, M and Das, A and Jha, SK}, title = {Electrostatic Modulation of Intramolecular and Intermolecular Interactions during the Formation of an Amyloid-like Assembly.}, journal = {Biochemistry}, volume = {62}, number = {12}, pages = {1890-1905}, doi = {10.1021/acs.biochem.3c00014}, pmid = {37246507}, issn = {1520-4995}, mesh = {Static Electricity ; *Protein Aggregates ; *Amyloid/chemistry ; Amyloidogenic Proteins ; DNA-Binding Proteins/chemistry ; Protein Folding ; }, abstract = {The mechanism of protein aggregation can be broadly viewed as a shift from the native-state stabilizing intramolecular to the aggregated-phase sustaining intermolecular interactions. Understanding the role of electrostatic forces on the extent of modulation of this switch has recently evolved as a topic of monumental significance as protein aggregation has lately been connected to charge modifications of an aging proteome. To decipher the distinctive role of electrostatic forces on the extremely complicated phase separation landscape, we opted for a combined in vitro-in silico approach to ascertain the structure-dynamics-stability-aggregability relationship of the functional tandem RRM domains of the ALS-related protein TDP-43 (TDP-43[tRRM]), under a bivariate solution condition in terms of pH and salt concentration. Under acidic pH conditions, the native TDP-43[tRRM] protein creates an aggregation-prone entropically favorable partially unfolded conformational landscape due to enthalpic destabilization caused by the protonation of the buried ionizable residues and consequent overwhelming fluctuations of selective segments of the sequence leading to anti-correlated movements of the two domains of the protein. The evolved fluffy ensemble with a comparatively exposed backbone then easily interacts with incoming protein molecules in the presence of salt via typical amyloid-aggregate-like intermolecular backbone hydrogen bonds with a considerable contribution originating from the dispersion forces. Subsequent exposure to excess salt at low pH conditions expedites the aggregation process via an electrostatic screening mechanism where salt shows preferential binding to the positively charged side chain. The applied target observable-specific approach complementarity unveils the hidden information landscape of an otherwise complex process with unquestionable conviction.}, } @article {pmid37245265, year = {2023}, author = {Biglari, N and Mehdizadeh, A and Vafaei Mastanabad, M and Gharaeikhezri, MH and Gol Mohammad Pour Afrakoti, L and Pourbala, H and Yousefi, M and Soltani-Zangbar, MS}, title = {Application of mesenchymal stem cells (MSCs) in neurodegenerative disorders: History, findings, and prospective challenges.}, journal = {Pathology, research and practice}, volume = {247}, number = {}, pages = {154541}, doi = {10.1016/j.prp.2023.154541}, pmid = {37245265}, issn = {1618-0631}, mesh = {Humans ; Prospective Studies ; *Neurodegenerative Diseases/metabolism/therapy ; *Mesenchymal Stem Cells/metabolism ; *Parkinson Disease ; *Alzheimer Disease/metabolism ; }, abstract = {Over the past few decades, the application of mesenchymal stem cells has captured the attention of researchers and practitioners worldwide. These cells can be obtained from practically every tissue in the body and are used to treat a broad variety of conditions, most notably neurological diseases such as Parkinson's disease, multiple sclerosis, amyotrophic lateral sclerosis, and Alzheimer's disease. Studies are still being conducted, and the results of these studies have led to the identification of several different molecular pathways involved in the neuroglial speciation process. These molecular systems are closely regulated and interconnected due to the coordinated efforts of many components that make up the machinery responsible for cell signaling. Within the scope of this study, we compared and contrasted the numerous mesenchymal cell sources and their cellular features. These many sources of mesenchymal cells included adipocyte cells, fetal umbilical cord tissue, and bone marrow. In addition, we investigated whether these cells can potentially treat and modify neurodegenerative illnesses.}, } @article {pmid37245191, year = {2023}, author = {Louapre, C and Rosenzwajg, M and Golse, M and Roux, A and Pitoiset, F and Adda, L and Tchitchek, N and Papeix, C and Maillart, E and Ungureanu, A and Charbonnier-Beaupel, F and Galanaud, D and Corvol, JC and Vicaut, E and Lubetzki, C and Klatzmann, D}, title = {A randomized double-blind placebo-controlled trial of low-dose interleukin-2 in relapsing-remitting multiple sclerosis.}, journal = {Journal of neurology}, volume = {270}, number = {9}, pages = {4403-4414}, pmid = {37245191}, issn = {1432-1459}, support = {ANR-16-RHUS-0001//ANR/ ; }, mesh = {Female ; Humans ; Double-Blind Method ; Interleukin-2/therapeutic use ; *Multiple Sclerosis ; *Multiple Sclerosis, Relapsing-Remitting/diagnostic imaging/drug therapy ; Treatment Outcome ; Male ; Adult ; }, abstract = {BACKGROUND: Multiple sclerosis (MS) is associated with regulatory T cells (Tregs) insufficiency while low-dose interleukin-2 (IL2LD) activates Tregs and reduces disease activity in autoimmune diseases.

METHODS: We aimed at addressing whether IL2LD improved Tregs from MS patients. MS-IL2 was a single-center double-blind phase-2 study. Thirty patients (mean [SD] age 36.8 years [8.3], 16 female) with relapsing-remitting MS with new MRI lesions within 6 months before inclusion were randomly assigned in a 1:1 ratio to placebo or IL-2 at 1 million IU, daily for 5 days and then fortnightly for 6 months. The primary endpoint was change in Tregs at day-5.

RESULTS: Unlike previous trials of IL2LD in more than 20 different autoimmune diseases, Tregs were not expanded at day-5 in IL2LD group, but only at day-15 (median [IQR] fold change from baseline: 1.26 [1.21-1.33] in IL2LD group; 1.01 [0.95-1.05] in placebo group, p < 0.001). At day-5, however, Tregs had acquired an activated phenotype (fold change of CD25 expression in Tregs: 2.17 [1.70-3.55] in IL2LD versus 0.97 [0.86-1.28] in placebo group, p < 0.0001). Regulator/effector T cells ratio remained elevated throughout treatment period in the IL2LD group (p < 0.001). Number of new active brain lesions and of relapses tended to be reduced in IL2LD treated patients, but the difference did not reach significance in this trial not powered to detect clinical efficacy.

CONCLUSION: The effect of IL2LD on Tregs in MS patients was modest and delayed, compared to other auto-immune diseases. This, together with findings that Tregs improve remyelination in MS models and recent reports of IL2LD efficacy in amyotrophic lateral sclerosis, warrants larger studies of IL2LD in MS, notably with increased dosages and/or modified modalities of administration.

ClinicalTrials.gov: NCT02424396; EU Clinical trials Register: 2014-000088-42.}, } @article {pmid37245090, year = {2023}, author = {Quintana, M and Saville, BR and Vestrucci, M and Detry, MA and Chibnik, L and Shefner, J and Berry, JD and Chase, M and Andrews, J and Sherman, AV and Yu, H and Drake, K and Cudkowicz, M and Paganoni, S and Macklin, EA and , }, title = {Design and Statistical Innovations in a Platform Trial for Amyotrophic Lateral Sclerosis.}, journal = {Annals of neurology}, volume = {94}, number = {3}, pages = {547-560}, doi = {10.1002/ana.26714}, pmid = {37245090}, issn = {1531-8249}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy ; Bayes Theorem ; Disease Progression ; Time Factors ; Clinical Trials as Topic ; Adaptive Clinical Trials as Topic ; }, abstract = {Platform trials allow efficient evaluation of multiple interventions for a specific disease. The HEALEY ALS Platform Trial is testing multiple investigational products in parallel and sequentially in persons with amyotrophic lateral sclerosis (ALS) with the goal of rapidly identifying novel treatments to slow disease progression. Platform trials have considerable operational and statistical efficiencies compared with typical randomized controlled trials due to their use of shared infrastructure and shared control data. We describe the statistical approaches required to achieve the objectives of a platform trial in the context of ALS. This includes following regulatory guidance for the disease area of interest and accounting for potential differences in outcomes of participants within the shared control (potentially due to differences in time of randomization, mode of administration, and eligibility criteria). Within the HEALEY ALS Platform Trial, the complex statistical objectives are met using a Bayesian shared parameter analysis of function and survival. This analysis serves to provide a common integrated estimate of treatment benefit, overall slowing in disease progression, as measured by function and survival while accounting for potential differences in the shared control group using Bayesian hierarchical modeling. Clinical trial simulation is used to provide a better understanding of this novel analysis method and complex design. ANN NEUROL 2023;94:547-560.}, } @article {pmid37244664, year = {2023}, author = {Carabajal, MD and Vidal, RP and Arancibia, JA and Olivieri, AC}, title = {A new constraint to model background signals when processing chromatographic-spectral second-order data with multivariate curve resolution.}, journal = {Analytica chimica acta}, volume = {1266}, number = {}, pages = {341354}, doi = {10.1016/j.aca.2023.341354}, pmid = {37244664}, issn = {1873-4324}, abstract = {BACKGROUND: the chemometric processing of second-order chromatographic-spectral data is usually carried out with the aid of multivariate curve resolution-alternating least-squares (MCR-ALS). When baseline contributions occur in the data, the background profile retrieved with MCR-ALS may show abnormal lumps or negative dips at the position of the remaining component peaks.

RESULTS: The phenomenon is shown to be due to remaining rotational ambiguity in the obtained profiles, as confirmed by the estimation of the boundaries of the range of feasible bilinear profiles. To avoid the abnormal features in the retrieved profile, a new background interpolation constraint is proposed and described in detail. Both simulated and experimental data are employed to support the need of the new MCR-ALS constraint. In the latter case, the estimated analyte concentrations agreed with those previously reported.

SIGNIFICANCE: The developed procedure helps to reduce the extent of rotational ambiguity in the solution and to better interpret the results on physicochemical grounds.}, } @article {pmid37243816, year = {2023}, author = {Davidson, JM and Wu, SSL and Rayner, SL and Cheng, F and Duncan, K and Russo, C and Newbery, M and Ding, K and Scherer, NM and Balez, R and García-Redondo, A and Rábano, A and Rosa-Fernandes, L and Ooi, L and Williams, KL and Morsch, M and Blair, IP and Di Ieva, A and Yang, S and Chung, RS and Lee, A}, title = {The E3 Ubiquitin Ligase SCF Cyclin F Promotes Sequestosome-1/p62 Insolubility and Foci Formation and is Dysregulated in ALS and FTD Pathogenesis.}, journal = {Molecular neurobiology}, volume = {60}, number = {9}, pages = {5034-5054}, pmid = {37243816}, issn = {1559-1182}, support = {IG1910//Motor Neurone Disease Research Australia/ ; IG2029//Motor Neurone Disease Research Australia/ ; IG2036//Motor Neurone Disease Research Australia/ ; IG2221//Motor Neurone Disease Research Australia/ ; Phyllis Diana Seman MND Research Grant//Motor Neurone Disease Research Australia/ ; BLP1901//Motor Neurone Disease Research Australia/ ; IG2308//Motor Neurone Disease Research Australia/ ; APP1095215//National Health and Medical Research Council/ ; APP1107644//National Health and Medical Research Council/ ; APP1176913//National Health and Medical Research Council/ ; APP2020035//National Health and Medical Research Council/ ; }, mesh = {Humans ; *Frontotemporal Dementia/genetics/pathology ; *Amyotrophic Lateral Sclerosis/metabolism ; Ubiquitin-Protein Ligases/metabolism ; Cyclins/metabolism ; Ubiquitination ; Mutation/genetics ; }, abstract = {Amyotrophic lateral sclerosis (ALS)- and frontotemporal dementia (FTD)-linked mutations in CCNF have been shown to cause dysregulation to protein homeostasis. CCNF encodes for cyclin F, which is part of the cyclin F-E3 ligase complex SCF[cyclinF] known to ubiquitylate substrates for proteasomal degradation. In this study, we identified a function of cyclin F to regulate substrate solubility and show how cyclin F mechanistically underlies ALS and FTD disease pathogenesis. We demonstrated that ALS and FTD-associated protein sequestosome-1/p62 (p62) was a canonical substrate of cyclin F which was ubiquitylated by the SCF[cyclinF] complex. We found that SCF[cyclin F] ubiquitylated p62 at lysine(K)281, and that K281 regulated the propensity of p62 to aggregate. Further, cyclin F expression promoted the aggregation of p62 into the insoluble fraction, which corresponded to an increased number of p62 foci. Notably, ALS and FTD-linked mutant cyclin F p.S621G aberrantly ubiquitylated p62, dysregulated p62 solubility in neuronal-like cells, patient-derived fibroblasts and induced pluripotent stem cells and dysregulated p62 foci formation. Consistently, motor neurons from patient spinal cord tissue exhibited increased p62 ubiquitylation. We suggest that the p.S621G mutation impairs the functions of cyclin F to promote p62 foci formation and shift p62 into the insoluble fraction, which may be associated to aberrant mutant cyclin F-mediated ubiquitylation of p62. Given that p62 dysregulation is common across the ALS and FTD spectrum, our study provides insights into p62 regulation and demonstrates that ALS and FTD-linked cyclin F mutant p.S621G can drive p62 pathogenesis associated with ALS and FTD.}, } @article {pmid37243319, year = {2023}, author = {Elmansy, MF and Reidl, CT and Rahaman, M and Özdinler, PH and Silverman, RB}, title = {Small molecules targeting different cellular pathologies for the treatment of amyotrophic lateral sclerosis.}, journal = {Medicinal research reviews}, volume = {43}, number = {6}, pages = {2260-2302}, pmid = {37243319}, issn = {1098-1128}, support = {R01 AG061708/AG/NIA NIH HHS/United States ; }, mesh = {Animals ; Humans ; *Amyotrophic Lateral Sclerosis/drug therapy/genetics ; *Neurodegenerative Diseases/metabolism ; Disease Models, Animal ; Motor Neurons/metabolism/pathology ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease in which the motor neuron circuitry displays progressive degeneration, affecting mostly the motor neurons in the brain and in the spinal cord. There are no effective cures, albeit three drugs, riluzole, edaravone, and AMX0035 (a combination of sodium phenylbutyrate and taurursodiol), have been approved by the Food and Drug Administration, with limited improvement in patients. There is an urgent need to build better and more effective treatment strategies for ALS. Since the disease is very heterogenous, numerous approaches have been explored, such as targeting genetic mutations, decreasing oxidative stress and excitotoxicity, enhancing mitochondrial function and protein degradation mechanisms, and inhibiting neuroinflammation. In addition, various chemical libraries or previously identified drugs have been screened for potential repurposing in the treatment of ALS. Here, we review previous drug discovery efforts targeting a variety of cellular pathologies that occur from genetic mutations that cause ALS, such as mutations in SOD1, C9orf72, FUS, and TARDP-43 genes. These mutations result in protein aggregation, which causes neuronal degeneration. Compounds used to target cellular pathologies that stem from these mutations are discussed and comparisons among different preclinical models are presented. Because the drug discovery landscape for ALS and other motor neuron diseases is changing rapidly, we also offer recommendations for a novel, more effective, direction in ALS drug discovery that could accelerate translation of effective compounds from animals to patients.}, } @article {pmid37240836, year = {2023}, author = {Barbieri, R and Nizzari, M and Zanardi, I and Pusch, M and Gavazzo, P}, title = {Voltage-Gated Sodium Channel Dysfunctions in Neurological Disorders.}, journal = {Life (Basel, Switzerland)}, volume = {13}, number = {5}, pages = {}, pmid = {37240836}, issn = {2075-1729}, abstract = {The pore-forming subunits (α subunits) of voltage-gated sodium channels (VGSC) are encoded in humans by a family of nine highly conserved genes. Among them, SCN1A, SCN2A, SCN3A, and SCN8A are primarily expressed in the central nervous system. The encoded proteins Nav1.1, Nav1.2, Nav1.3, and Nav1.6, respectively, are important players in the initiation and propagation of action potentials and in turn of the neural network activity. In the context of neurological diseases, mutations in the genes encoding Nav1.1, 1.2, 1.3 and 1.6 are responsible for many forms of genetic epilepsy and for Nav1.1 also of hemiplegic migraine. Several pharmacological therapeutic approaches targeting these channels are used or are under study. Mutations of genes encoding VGSCs are also involved in autism and in different types of even severe intellectual disability (ID). It is conceivable that in these conditions their dysfunction could indirectly cause a certain level of neurodegenerative processes; however, so far, these mechanisms have not been deeply investigated. Conversely, VGSCs seem to have a modulatory role in the most common neurodegenerative diseases such as Alzheimer's, where SCN8A expression has been shown to be negatively correlated with disease severity.}, } @article {pmid37240666, year = {2023}, author = {González-Mingot, C and Miana-Mena, FJ and Iñarrea, PJ and Iñiguez, C and Capablo, JL and Osta, R and Gil-Sánchez, A and Brieva, L and Larrodé, P}, title = {Mitochondrial Aconitase Enzymatic Activity: A Potential Long-Term Survival Biomarker in the Blood of ALS Patients.}, journal = {Journal of clinical medicine}, volume = {12}, number = {10}, pages = {}, pmid = {37240666}, issn = {2077-0383}, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a multisystemic, progressive, neurodegenerative disorder. Despite it being generally fatal within a period of 2-4 years, it is highly heterogeneous; as a result, survival periods may vary greatly among individual patients. Biomarkers can serve as tools for diagnosis, prognosis, indicators of therapeutic response, and future therapeutics. Free-radical-dependent mitochondrial damage is believed to play a crucial role in neurodegeneration in ALS. Mitochondrial aconitase, which is also known as aconitase 2 (Aco2), is a key Krebs cycle enzyme and is involved in the regulation of cellular metabolism and iron homeostasis. Aco2 is very sensitive to oxidative inactivation and can aggregate and accumulate in the mitochondrial matrix, causing mitochondrial dysfunction. Loss of Aco2 activity may therefore reflect increased levels of mitochondrial dysfunction due to oxidative damage and could be relevant to ALS pathogenesis. The aim of our study was to confirm changes in mitochondrial aconitase activity in peripheral blood and to determine whether such changes are dependent on, or independent of, the patient's condition and to propose the feasibility of using them as possible valid biomarkers to quantify the progression of the disease and as a predictor of individual prognosis in ALS.

METHODS: We measured the Aco2 enzymatic activity in the platelets of blood samples taken from 22 controls and 26 ALS patients at different stages of disease development. We then correlated antioxidant activity with clinical and prognostic variables.

RESULTS: Aco2 activity was significantly lower in the 26 ALS patients than in the 22 controls (p < 0.05). Patients with higher levels of Aco2 activity survived longer than those with lower levels (p < 0.05). Aco2 activity was also higher in patients with earlier onset (p < 0.05) and in those with predominantly upper motor neuron signs.

CONCLUSIONS: Aco2 activity seems to be an independent factor that could be used in the long-term survival prognosis of ALS. Our findings suggest that blood Aco2 could be a leading candidate for use as a biomarker to improve prognosis. More studies are needed to confirm these results.}, } @article {pmid37240459, year = {2023}, author = {Carlucci, A and Fusar Poli, B}, title = {Getting It Right in Restrictive Lung Disease.}, journal = {Journal of clinical medicine}, volume = {12}, number = {10}, pages = {}, pmid = {37240459}, issn = {2077-0383}, abstract = {Restrictive lung disease (predominantly in patients with neuromuscular disease (NMD) and ribcage deformity) may induce chronic hypercapnic respiratory failure, which represents an absolute indication to start home NIV (HNIV). However, in the early phases of NMD, patients may present only diurnal symptoms or orthopnoea and sleep disturbances with normal diurnal gas exchange. The evaluation of respiratory function decline may predict the presence of sleep disturbances (SD) and nocturnal hypoventilation that can be respectively diagnosed with polygraphy and PCO2 transcutaneous monitoring. If nocturnal hypoventilation and/or apnoea/hypopnea syndrome are detected, HNIV should be introduced. Once HNIV has been started, adequate follow-up is mandatory. The ventilator's built-in software provides important information about patient adherence and eventual leaks to correct. Detailed data about pressure and flow curves may suggest the presence of upper airway obstruction (UAO) during NIV that may occur with or without decrease in respiratory drive. Etiology and treatment of these two different forms of UAO are different. For this reason, in some circumstances, it might be useful to perform a polygraph. PtCO2 monitoring, together with pulse-oximetry, seem to be very important tools to optimize HNIV. The role of HNIV in neuromuscular disease is to correct diurnal and nocturnal hypoventilation with the consequence of improving quality of life, symptoms, and survival.}, } @article {pmid37240370, year = {2023}, author = {Mukhamedyarov, MA and Khabibrakhmanov, AN and Khuzakhmetova, VF and Giniatullin, AR and Zakirjanova, GF and Zhilyakov, NV and Mukhutdinova, KA and Samigullin, DV and Grigoryev, PN and Zakharov, AV and Zefirov, AL and Petrov, AM}, title = {Early Alterations in Structural and Functional Properties in the Neuromuscular Junctions of Mutant FUS Mice.}, journal = {International journal of molecular sciences}, volume = {24}, number = {10}, pages = {}, pmid = {37240370}, issn = {1422-0067}, support = {21-14-00044//Russian Science Foundation/ ; contract 1/22-3 dated July 13, 2022//Kazan State Medical University/ ; }, mesh = {Animals ; Mice ; *Amyotrophic Lateral Sclerosis/genetics ; Neuromuscular Junction/metabolism ; Neurotransmitter Agents/metabolism ; RNA-Binding Protein FUS/genetics ; Synapsins/genetics/metabolism ; Disease Models, Animal ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is manifested as skeletal muscle denervation, loss of motor neurons and finally severe respiratory failure. Mutations of RNA-binding protein FUS are one of the common genetic reasons of ALS accompanied by a 'dying back' type of degeneration. Using fluorescent approaches and microelectrode recordings, the early structural and functional alterations in diaphragm neuromuscular junctions (NMJs) were studied in mutant FUS mice at the pre-onset stage. Lipid peroxidation and decreased staining with a lipid raft marker were found in the mutant mice. Despite the preservation of the end-plate structure, immunolabeling revealed an increase in levels of presynaptic proteins, SNAP-25 and synapsin 1. The latter can restrain Ca[2+]-dependent synaptic vesicle mobilization. Indeed, neurotransmitter release upon intense nerve stimulation and its recovery after tetanus and compensatory synaptic vesicle endocytosis were markedly depressed in FUS mice. There was a trend to attenuation of axonal [Ca[2+]]in increase upon nerve stimulation at 20 Hz. However, no changes in neurotransmitter release and the intraterminal Ca[2+] transient in response to low frequency stimulation or in quantal content and the synchrony of neurotransmitter release at low levels of external Ca[2+] were detected. At a later stage, shrinking and fragmentation of end plates together with a decrease in presynaptic protein expression and disturbance of the neurotransmitter release timing occurred. Overall, suppression of synaptic vesicle exo-endocytosis upon intense activity probably due to alterations in membrane properties, synapsin 1 levels and Ca[2+] kinetics could be an early sign of nascent NMJ pathology, which leads to neuromuscular contact disorganization.}, } @article {pmid37240368, year = {2023}, author = {Singh, J and Goodman-Vincent, E and Santosh, P}, title = {Evidence Synthesis of Gene Therapy and Gene Editing from Different Disorders-Implications for Individuals with Rett Syndrome: A Systematic Review.}, journal = {International journal of molecular sciences}, volume = {24}, number = {10}, pages = {}, pmid = {37240368}, issn = {1422-0067}, support = {RE16403//Reverse Rett/ ; RE16403//Reverse Rett/ ; }, mesh = {Humans ; *Rett Syndrome/therapy/drug therapy ; Gene Editing ; Tissue Distribution ; Methyl-CpG-Binding Protein 2/genetics/metabolism ; Brain/metabolism ; Genetic Therapy ; }, abstract = {This systematic review and thematic analysis critically evaluated gene therapy trials in amyotrophic lateral sclerosis, haemoglobinopathies, immunodeficiencies, leukodystrophies, lysosomal storage disorders and retinal dystrophies and extrapolated the key clinical findings to individuals with Rett syndrome (RTT). The PRISMA guidelines were used to search six databases during the last decade, followed by a thematic analysis to identify the emerging themes. Thematic analysis across the different disorders revealed four themes: (I) Therapeutic time window of gene therapy; (II) Administration and dosing strategies for gene therapy; (III) Methods of gene therapeutics and (IV) Future areas of clinical interest. Our synthesis of information has further enriched the current clinical evidence base and can assist in optimising gene therapy and gene editing studies in individuals with RTT, but it would also benefit when applied to other disorders. The findings suggest that gene therapies have better outcomes when the brain is not the primary target. Across different disorders, early intervention appears to be more critical, and targeting the pre-symptomatic stage might prevent symptom pathology. Intervention at later stages of disease progression may benefit by helping to clinically stabilise patients and preventing disease-related symptoms from worsening. If gene therapy or editing has the desired outcome, older patients would need concerted rehabilitation efforts to reverse their impairments. The timing of intervention and the administration route would be critical parameters for successful outcomes of gene therapy/editing trials in individuals with RTT. Current approaches also need to overcome the challenges of MeCP2 dosing, genotoxicity, transduction efficiencies and biodistribution.}, } @article {pmid37240018, year = {2023}, author = {Pardo-Moreno, T and Mohamed-Mohamed, H and Suleiman-Martos, S and Ramos-Rodriguez, JJ and Rivas-Dominguez, A and Melguizo-Rodríguez, L and Gómez-Urquiza, JL and Bermudez-Pulgarin, B and Garcia-Morales, V}, title = {Amyotrophic Lateral Sclerosis and Serum Lipid Level Association: A Systematic Review and Meta-Analytic Study.}, journal = {International journal of molecular sciences}, volume = {24}, number = {10}, pages = {}, pmid = {37240018}, issn = {1422-0067}, support = {P18-RT-3324//Regional Government of Andalusia/ ; 20-01293 and PECART-0096-2020//Regional Government of Andalusia/ ; P20-01061//Regional Government of Andalusia/ ; PID2019-110960GB-I00//Ministry of Science and Innovation, Spain/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis ; *Neurodegenerative Diseases ; Triglycerides ; Cholesterol, HDL ; Cholesterol, LDL ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with unknown etiology. Many metabolic alterations occur during ALS progress and can be used as a method of pre-diagnostic and early diagnosis. Dyslipidemia is one of the physiological changes observed in numerous ALS patients. The aim of this study is to analyze the possible relationship between the rate of disease progression (functional rating scale (ALS-FRS)) and the plasma lipid levels at the early stage of ALS. A systematic review was carried out in July 2022. The search equation was "Triglycerides AND amyotrophic lateral sclerosis" and its variants. Four meta-analyses were performed. Four studies were included in the meta-analysis. No significant differences were observed between the lipid levels (total cholesterol, triglycerides, HDL cholesterol, and LDL cholesterol) and the ALS-FRS score at the onset of the disease. Although the number of studies included in this research was low, the results of this meta-analytic study suggest that there is no clear relationship between the symptoms observed in ALS patients and the plasma lipid levels. An increase in research, as well as an expansion of the geographical area, would be of interest.}, } @article {pmid37239468, year = {2023}, author = {Hedges, EC and Cocks, G and Shaw, CE and Nishimura, AL}, title = {Generation of an Open-Access Patient-Derived iPSC Biobank for Amyotrophic Lateral Sclerosis Disease Modelling.}, journal = {Genes}, volume = {14}, number = {5}, pages = {}, pmid = {37239468}, issn = {2073-4425}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/metabolism ; *Induced Pluripotent Stem Cells/metabolism ; *Neurodegenerative Diseases/metabolism ; Biological Specimen Banks ; Motor Neurons/metabolism ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease affecting the upper and lower motor neurons, causing patients to lose control over voluntary movement, and leading to gradual paralysis and death. There is no cure for ALS, and the development of viable therapeutics has proved challenging, demonstrated by a lack of positive results from clinical trials. One strategy to address this is to improve the tool kit available for pre-clinical research. Here, we describe the creation of an open-access ALS iPSC biobank generated from patients carrying mutations in the TARDBP, FUS, ANXA11, ARPP21, and C9ORF72 genes, alongside healthy controls. To demonstrate the utilisation of these lines for ALS disease modelling, a subset of FUS-ALS iPSCs were differentiated into functionally active motor neurons. Further characterisation revealed an increase in cytoplasmic FUS protein and reduced neurite outgrowth in FUS-ALS motor neurons compared to the control. This proof-of-principle study demonstrates that these novel patient-derived iPSC lines can recapitulate specific and early disease-related ALS phenotypes. This biobank provides a disease-relevant platform for discovery of ALS-associated cellular phenotypes to aid the development of novel treatment strategies.}, } @article {pmid37239275, year = {2023}, author = {Chen, H and Hu, Z and Ke, Z and Xu, Y and Bai, F and Liu, Z}, title = {Aberrant Multimodal Connectivity Pattern Involved in Default Mode Network and Limbic Network in Amyotrophic Lateral Sclerosis.}, journal = {Brain sciences}, volume = {13}, number = {5}, pages = {}, pmid = {37239275}, issn = {2076-3425}, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder that progressively affects bulbar and limb function. Despite increasing recognition of the disease as a multinetwork disorder characterized by aberrant structural and functional connectivity, its integrity agreement and its predictive value for disease diagnosis remain to be fully elucidated. In this study, we recruited 37 ALS patients and 25 healthy controls (HCs). High-resolution 3D T1-weighted imaging and resting-state functional magnetic resonance imaging were, respectively, applied to construct multimodal connectomes. Following strict neuroimaging selection criteria, 18 ALS and 25 HC patients were included. Network-based statistic (NBS) and the coupling of grey matter structural-functional connectivity (SC-FC coupling) were performed. Finally, the support vector machine (SVM) method was used to distinguish the ALS patients from HCs. Results showed that, compared with HCs, ALS individuals exhibited a significantly increased functional network, predominantly encompassing the connections between the default mode network (DMN) and the frontoparietal network (FPN). The increased structural connections predominantly involved the inter-regional connections between the limbic network (LN) and the DMN, the salience/ventral attention network (SVAN) and FPN, while the decreased structural connections mainly involved connections between the LN and the subcortical network (SN). We also found increased SC-FC coupling in DMN-related brain regions and decoupling in LN-related brain regions in ALS, which could differentiate ALS from HCs with promising capacity based on SVM. Our findings highlight that DMN and LN may play a vital role in the pathophysiological mechanism of ALS. Additionally, SC-FC coupling could be regarded as a promising neuroimaging biomarker for ALS and shows important clinical potential for early recognition of ALS individuals.}, } @article {pmid37239045, year = {2023}, author = {Ferecskó, AS and Smallwood, MJ and Moore, A and Liddle, C and Newcombe, J and Holley, J and Whatmore, J and Gutowski, NJ and Eggleton, P}, title = {STING-Triggered CNS Inflammation in Human Neurodegenerative Diseases.}, journal = {Biomedicines}, volume = {11}, number = {5}, pages = {}, pmid = {37239045}, issn = {2227-9059}, abstract = {BACKGROUND: Some neurodegenerative diseases have an element of neuroinflammation that is triggered by viral nucleic acids, resulting in the generation of type I interferons. In the cGAS-STING pathway, microbial and host-derived DNA bind and activate the DNA sensor cGAS, and the resulting cyclic dinucleotide, 2'3-cGAMP, binds to a critical adaptor protein, stimulator of interferon genes (STING), which leads to activation of downstream pathway components. However, there is limited work demonstrating the activation of the cGAS-STING pathway in human neurodegenerative diseases.

METHODS: Post-mortem CNS tissue from donors with multiple sclerosis (n = 4), Alzheimer's disease (n = 6), Parkinson's disease (n = 3), amyotrophic lateral sclerosis (n = 3) and non-neurodegenerative controls (n = 11) were screened by immunohistochemistry for STING and relevant protein aggregates (e.g., amyloid-β, α-synuclein, TDP-43). Human brain endothelial cells were cultured and stimulated with the STING agonist palmitic acid (1-400 μM) and assessed for mitochondrial stress (release of mitochondrial DNA into cytosol, increased oxygen consumption), downstream regulator factors, TBK-1/pIRF3 and inflammatory biomarker interferon-β release and changes in ICAM-1 integrin expression.

RESULTS: In neurodegenerative brain diseases, elevated STING protein was observed mainly in brain endothelial cells and neurons, compared to non-neurodegenerative control tissues where STING protein staining was weaker. Interestingly, a higher STING presence was associated with toxic protein aggregates (e.g., in neurons). Similarly high STING protein levels were observed within acute demyelinating lesions in multiple sclerosis subjects. To understand non-microbial/metabolic stress activation of the cGAS-STING pathway, brain endothelial cells were treated with palmitic acid. This evoked mitochondrial respiratory stress up to a ~2.5-fold increase in cellular oxygen consumption. Palmitic acid induced a statistically significant increase in cytosolic DNA leakage from endothelial cell mitochondria (Mander's coefficient; p < 0.05) and a significant increase in TBK-1, phosphorylated transcription factor IFN regulatory factor 3, cGAS and cell surface ICAM. In addition, a dose response in the secretion of interferon-β was observed, but it failed to reach statistical significance.

CONCLUSIONS: The histological evidence shows that the common cGAS-STING pathway appears to be activated in endothelial and neural cells in all four neurodegenerative diseases examined. Together with the in vitro data, this suggests that the STING pathway might be activated via perturbation of mitochondrial stress and DNA leakage, resulting in downstream neuroinflammation; hence, this pathway may be a target for future STING therapeutics.}, } @article {pmid37239030, year = {2023}, author = {Wang, W and Zhang, L and Xia, K and Huang, T and Fan, D}, title = {Mendelian Randomization Analysis Reveals Statins Potentially Increase Amyotrophic Lateral Sclerosis Risk Independent of Peripheral Cholesterol-Lowering Effects.}, journal = {Biomedicines}, volume = {11}, number = {5}, pages = {}, pmid = {37239030}, issn = {2227-9059}, support = {82101489, 81873784, 82071426//National Natural Science Foundation of China/ ; 2021M690255//China Postdoctoral Science Foundation/ ; }, abstract = {BACKGROUND: Observational studies suggest that statins may affect amyotrophic lateral sclerosis (ALS). However, they are limited by confounding and reverse causality biases. Therefore, we aimed to investigate the potential causal associations between statins and ALS using a mendelian randomization (MR) approach.

METHODS: Two-sample MR and drug-target MR were performed. Exposure sources included GWAS summary statistics of statin use, low-density-lipoprotein cholesterol (LDL-C), HMGCR-mediated LDL-C and LDL-C response to statins.

RESULTS: Genetic predisposition to statin medication was associated with increased ALS risk (OR = 1.085, 95% CI = 1.025-1.148, p = 0.005). After removing SNPs significantly associated with statin use from the instrumental variables (IVs), LDL-C-related higher ALS risk was absent (before removing: OR = 1.075, 95% CI = 1.013-1.141, p = 0.017; after removing: OR = 1.036, 95% CI = 0.949-1.131, p = 0.432). HMGCR-mediated LDL-C (OR = 1.033, 95% CI = 0.823-1.296, p = 0.779) and blood LDL-C response to statins (OR = 0.998, 95% CI = 0.991-1.005, p = 0.538) had no association with ALS.

CONCLUSIONS: Here, we show that statins may be a risky exposure that increases ALS risk independent of the lowering effect of LDL-C in peripheral circulation. This provides insights into ALS development and prevention.}, } @article {pmid37238987, year = {2023}, author = {Ravnik Glavač, M and Mezzavilla, M and Dolinar, A and Koritnik, B and Glavač, D}, title = {Aberrantly Expressed Hsa_circ_0060762 and CSE1L as Potential Peripheral Blood Biomarkers for ALS.}, journal = {Biomedicines}, volume = {11}, number = {5}, pages = {}, pmid = {37238987}, issn = {2227-9059}, support = {P3-0054, P3-0338, P1-0170, AD PhD thesis grant//Slovenian Research Agency/ ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a rapidly progressive adult-onset neurodegenerative disease that is often diagnosed with a delay due to initial non-specific symptoms. Therefore, reliable and easy-to-obtain biomarkers are an absolute necessity for earlier and more accurate diagnostics. Circular RNAs (circRNAs) have already been proposed as potential biomarkers for several neurodegenerative diseases. In this study, we further investigated the usefulness of circRNAs as potential biomarkers for ALS. We first performed a microarray analysis of circRNAs on peripheral blood mononuclear cells of a subset of ALS patients and controls. Among the differently expressed circRNA by microarray analysis, we selected only the ones with a host gene that harbors the highest level of conservation and genetic constraints. This selection was based on the hypothesis that genes under selective pressure and genetic constraints could have a major role in determining a trait or disease. Then we performed a linear regression between ALS cases and controls using each circRNA as a predictor variable. With a False Discovery Rate (FDR) threshold of 0.1, only six circRNAs passed the filtering and only one of them remained statistically significant after Bonferroni correction: hsa_circ_0060762 and its host gene CSE1L. Finally, we observed a significant difference in expression levels between larger sets of patients and healthy controls for both hsa_circ_0060762 and CSE1L. CSE1L is a member of the importin β family and mediates inhibition of TDP-43 aggregation; the central pathogenicity in ALS and hsa_circ_0060762 has binding sites for several miRNAs that have been already proposed as biomarkers for ALS. In addition, receiver operating characteristics curve analysis showed diagnostic potential for CSE1L and hsa_circ_0060762. Hsa_circ_0060762 and CSE1L thus represent novel potential peripheral blood biomarkers and therapeutic targets for ALS.}, } @article {pmid37238921, year = {2023}, author = {Oh, S and Jang, Y and Na, CH}, title = {Discovery of Biomarkers for Amyotrophic Lateral Sclerosis from Human Cerebrospinal Fluid Using Mass-Spectrometry-Based Proteomics.}, journal = {Biomedicines}, volume = {11}, number = {5}, pages = {}, pmid = {37238921}, issn = {2227-9059}, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by the loss of upper and lower motor neurons, which eventually may lead to death. Critical to the mission of developing effective therapies for ALS is the discovery of biomarkers that can illuminate mechanisms of neurodegeneration and have diagnostic, prognostic, or pharmacodynamic value. Here, we merged unbiased discovery-based approaches and targeted quantitative comparative analyses to identify proteins that are altered in cerebrospinal fluid (CSF) from patients with ALS. Mass spectrometry (MS)-based proteomic approaches employing tandem mass tag (TMT) quantification methods from 40 CSF samples comprising 20 patients with ALS and 20 healthy control (HC) individuals identified 53 proteins that are differential between the two groups after CSF fractionation. Notably, these proteins included both previously identified ones, validating our approach, and novel ones that have the potential for expanding biomarker repertoire. The identified proteins were subsequently examined using parallel reaction monitoring (PRM) MS methods on 61 unfractionated CSF samples comprising 30 patients with ALS and 31 HC individuals. Fifteen proteins (APOB, APP, CAMK2A, CHI3L1, CHIT1, CLSTN3, ERAP2, FSTL4, GPNMB, JCHAIN, L1CAM, NPTX2, SERPINA1, SERPINA3, and UCHL1) showed significant differences between ALS and the control. Taken together, this study identified multiple novel proteins that are altered in ALS, providing the foundation for developing new biomarkers for ALS.}, } @article {pmid37238732, year = {2023}, author = {Maksimovic, K and Youssef, M and You, J and Sung, HK and Park, J}, title = {Evidence of Metabolic Dysfunction in Amyotrophic Lateral Sclerosis (ALS) Patients and Animal Models.}, journal = {Biomolecules}, volume = {13}, number = {5}, pages = {}, pmid = {37238732}, issn = {2218-273X}, mesh = {Animals ; *Amyotrophic Lateral Sclerosis/metabolism ; *Neurodegenerative Diseases/metabolism ; Motor Neurons/metabolism ; Models, Animal ; Glucose/metabolism ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that affects motor neurons, leading to muscle weakness, paralysis, and eventual death. Research from the past few decades has appreciated that ALS is not only a disease of the motor neurons but also a disease that involves systemic metabolic dysfunction. This review will examine the foundational research of understanding metabolic dysfunction in ALS and provide an overview of past and current studies in ALS patients and animal models, spanning from full systems to various metabolic organs. While ALS-affected muscle tissue exhibits elevated energy demand and a fuel preference switch from glycolysis to fatty acid oxidation, adipose tissue in ALS undergoes increased lipolysis. Dysfunctions in the liver and pancreas contribute to impaired glucose homeostasis and insulin secretion. The central nervous system (CNS) displays abnormal glucose regulation, mitochondrial dysfunction, and increased oxidative stress. Importantly, the hypothalamus, a brain region that controls whole-body metabolism, undergoes atrophy associated with pathological aggregates of TDP-43. This review will also cover past and present treatment options that target metabolic dysfunction in ALS and provide insights into the future of metabolism research in ALS.}, } @article {pmid37238605, year = {2023}, author = {Zhang, H and Dai, S and Yang, Y and Wei, J and Li, X and Luo, P and Jiang, X}, title = {Role of Sirtuin 3 in Degenerative Diseases of the Central Nervous System.}, journal = {Biomolecules}, volume = {13}, number = {5}, pages = {}, pmid = {37238605}, issn = {2218-273X}, mesh = {Humans ; Central Nervous System/metabolism ; Mitochondria/metabolism ; *Neurodegenerative Diseases/metabolism ; *Parkinson Disease/metabolism ; *Sirtuin 3/metabolism ; }, abstract = {An NAD[+]-dependent deacetylase called Sirtuin 3 (Sirt3) is involved in the metabolic processes of the mitochondria, including energy generation, the tricarboxylic acid cycle, and oxidative stress. Sirt3 activation can slow down or prevent mitochondrial dysfunction in response to neurodegenerative disorders, demonstrating a strong neuroprotective impact. The mechanism of Sirt3 in neurodegenerative illnesses has been elucidated over time; it is essential for neuron, astrocyte, and microglial function, and its primary regulatory factors include antiapoptosis, oxidative stress, and the maintenance of metabolic homeostasis. Neurodegenerative disorders, such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS), may benefit from a thorough and in-depth investigation of Sirt3. In this review, we primarily cover Sirt3's role and its regulation in the nerve cells and the connection between Sirt3 and neurodegenerative disorders.}, } @article {pmid37237880, year = {2023}, author = {Wunsch, FT and Metzler-Nolte, N and Theiss, C and Matschke, V}, title = {Defects in Glutathione System in an Animal Model of Amyotrophic Lateral Sclerosis.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {12}, number = {5}, pages = {}, pmid = {37237880}, issn = {2076-3921}, abstract = {Amyotrophic lateral sclerosis (ALS) is a progredient neurodegenerative disease characterized by a degeneration of the first and second motor neurons. Elevated levels of reactive oxygen species (ROS) and decreased levels of glutathione, which are important defense mechanisms against ROS, have been reported in the central nervous system (CNS) of ALS patients and animal models. The aim of this study was to determine the cause of decreased glutathione levels in the CNS of the ALS model wobbler mouse. We analyzed changes in glutathione metabolism in the spinal cord, hippocampus, cerebellum, liver, and blood samples of the ALS model, wobbler mouse, using qPCR, Western Blot, HPLC, and fluorometric assays. Here, we show for the first time a decreased expression of enzymes involved in glutathione synthesis in the cervical spinal cord of wobbler mice. We provide evidence for a deficient glutathione metabolism, which is not restricted to the nervous system, but can be seen in various tissues of the wobbler mouse. This deficient system is most likely the reason for an inefficient antioxidative system and, thus, for elevated ROS levels.}, } @article {pmid37236359, year = {2023}, author = {Thornburg-Suresh, EJC and Richardson, JE and Summers, DW}, title = {The Stathmin-2 membrane-targeting domain is required for axon protection and regulated degradation by DLK signaling.}, journal = {The Journal of biological chemistry}, volume = {299}, number = {7}, pages = {104861}, pmid = {37236359}, issn = {1083-351X}, support = {R01 NS126191/NS/NINDS NIH HHS/United States ; }, mesh = {Humans ; *Stathmin/genetics/metabolism ; Axons/metabolism ; Neurons/metabolism ; Signal Transduction ; *Amyotrophic Lateral Sclerosis/metabolism ; MAP Kinase Kinase Kinases/metabolism ; }, abstract = {Axon integrity is essential for functional connectivity in the nervous system. The degeneration of stressed or damaged axons is a common and sometimes initiating event in neurodegenerative disorders. Stathmin-2 (Stmn2) is an axon maintenance factor that is depleted in amyotrophic lateral sclerosis, and replenishment of Stmn2 can restore neurite outgrowth in diseased neurons. However, mechanisms responsible for Stmn2-mediated axon maintenance in injured neurons are not known. We used primary sensory neurons to interrogate the role of Stmn2 in the degeneration of severed axons. We discover that membrane association of Stmn2 is critical for its axon-protective activity. Structure-function studies revealed that axonal enrichment of Stmn2 is driven by palmitoylation as well as tubulin interaction. Using live imaging, we discover that another Stmn, Stmn3, comigrates with Stmn2-containing vesicles. We also demonstrate that Stmn3 undergoes regulated degradation through dual leucine zipper kinase (DLK)-c-Jun N-terminal kinase signaling. The Stmn2 membrane-targeting domain is both necessary and sufficient for localization to a specific vesicle population and confers sensitivity to DLK-dependent degradation. Our findings reveal a broader role for DLK in tuning the local abundance of palmitoylated Stmns in axon segments. Moreover, palmitoylation is a critical component of Stmn-mediated axon protection, and defining the Stmn2-containing vesicle population will provide important clues toward mechanisms of axon maintenance.}, } @article {pmid37233619, year = {2023}, author = {Hrafnkelsdottir, AE and Bjornsson, HM and Oskarsson, JP and Runolfsson, S}, title = {[Training of Icelandic rural doctors in managing trauma and acute illness].}, journal = {Laeknabladid}, volume = {109}, number = {6}, pages = {283-290}, doi = {10.17992/lbl.2023.06.747}, pmid = {37233619}, issn = {1670-4959}, mesh = {Humans ; Child ; Iceland ; Emergencies ; Cross-Sectional Studies ; Acute Disease ; *General Practitioners ; *Rural Health Services ; }, abstract = {INTRODUCTION: Rural medicine is in many ways different from urban primary care. In addition to providing primary care for a population, the rural doctor is tasked with the initial evaluation and stabilization of all emergencies usually managed by an Emergency Department in urban areas. The goal of this study was to assess rural doctors' in Iceland attendance of courses in Emergency Medicine (EM), how rural doctors grade their own ability to respond to emergencies and evaluate their Continuous Medical Education (CME) within the field of EM.

MATERIALS AND METHODS: In this descriptive cross-sectional study, all rural general practitioners (GP) in Iceland with at least two years of experience post foundation training and who practiced at least a quarter of every year outside the capital area were surveyed using an electronic questionnaire. T-test and qi-square test were used for analysis and significance determined if p<0.05.

RESULTS: The survey was sent to 84 doctors with 47 (56%) completing the survey. Over 90% of the participants reported having completed a course in Advanced Life Support (ALS) but only 18% had completed a course in prehospital EM specifically designed for this group of doctors. Over half of the participants considered themselves to have good training to perform 7 out of 11 surveyed emergency procedures. Over 40% of participants considered it necessary to improve their CME in 7 out of 10 categories of EM. The majority of rural GPs considered shortage of doctors in the rural environment a significant factor limiting their CME.

CONCLUSIONS: The majority of rural doctors in Iceland consider themselves to have a good training to provide initial EM care in their community. Efforts to improve their training in this field of medicine should focus on scene safety and working in the prehospital setting, pediatrics, labor and deliveries and gynecological emergencies. Rural doctors need to have access to appropriate EM training courses.}, } @article {pmid37231286, year = {2023}, author = {Goudarzi, A and Agah, E and Ghajarzadeh, M and Jazani, MR and Sarraf, P}, title = {Clinical determinants of sleep quality in patients with amyotrophic lateral sclerosis.}, journal = {Sleep & breathing = Schlaf & Atmung}, volume = {27}, number = {6}, pages = {2517-2522}, pmid = {37231286}, issn = {1522-1709}, mesh = {Humans ; Sleep Quality ; *Amyotrophic Lateral Sclerosis/complications/diagnosis ; Severity of Illness Index ; Deglutition/physiology ; Patient Acuity ; *Sleep Wake Disorders/diagnosis/epidemiology/complications ; }, abstract = {OBJECTIVES: Poor sleep quality is more prevalent in patients with amyotrophic lateral sclerosis (ALS) than in healthy populations. The purpose of this study was to examine whether or not motor dysfunction at various distinct levels correlates with subjective sleep quality.

METHODS: Patients with ALS and controls were assessed using the Pittsburgh Sleep Quality Index (PSQI), ALS Functional Rating Scale Revised (ALSFRS-R), Beck Depression Inventory-II (BDI-II), and the Epworth Sleepiness Scale (ESS). The ALSFRS-R was used to obtain information on 12 different aspects of motor function in patients with ALS. We compared these data between the groups with poor and good sleep quality.

RESULTS: A total of 92 patients with ALS and 92 age- and sex-matched controls entered the study. The global PSQI score was significantly higher in patients with ALS than in healthy subjects (5.5 ± 4.2 vs. 4.0 ± 2.8) and 44% of the patients with ALS had poor sleep quality (PSQI score > 5). The sleep duration, sleep efficiency, and sleep disturbances components were significantly worse in patients with ALS. Sleep quality (PSQI) score correlated with ALSFRS-R score, BDI-II score, and ESS score. Of the 12 ALSFRS-R functions, swallowing significantly affected sleep quality. Orthopnea, speech, salivation, dyspnea, and walking had a medium effect. In addition, turning in bed, climbing stairs, and dressing and hygiene were found to have a small effect on sleep quality among patients with ALS.

CONCLUSIONS: Nearly half of our patients had poor sleep quality related to disease severity, depression, and daytime sleepiness. Bulbar muscle dysfunction may be associated with sleep disturbances in individuals with ALS, particularly when swallowing is impaired. In addition, patients suffering from axial or lower limb muscle disruptions are likely to have trouble sleeping.}, } @article {pmid37231108, year = {2023}, author = {Berriat, F and Lobsiger, CS and Boillée, S}, title = {The contribution of the peripheral immune system to neurodegeneration.}, journal = {Nature neuroscience}, volume = {26}, number = {6}, pages = {942-954}, pmid = {37231108}, issn = {1546-1726}, mesh = {Humans ; Central Nervous System ; *Alzheimer Disease/metabolism ; *Neurodegenerative Diseases/pathology ; *Amyotrophic Lateral Sclerosis/pathology ; Leukocytes/metabolism ; }, abstract = {Microglial cells are the major immune cells of the central nervous system (CNS), and directly react to neurodegeneration, but other immune cell types are also able to react to pathology and can modify the course of neurodegenerative processes. These mainly include monocytes/macrophages and lymphocytes. While these peripheral immune cells were initially considered to act only after infiltrating the CNS, recent evidence suggests that some of them can also act directly from the periphery. We will review the existing and emerging evidence for a role of peripheral immune cells in neurodegenerative diseases, both with and without CNS infiltration. Our focus will be on amyotrophic lateral sclerosis, but we will also compare to Alzheimer's disease and Parkinson's disease to highlight similarities or differences. Peripheral immune cells are easily accessible, and therefore may be an attractive therapeutic target for neurodegenerative diseases. Thus, understanding how these peripheral immune cells communicate with the CNS deserves deeper investigation.}, } @article {pmid37228467, year = {2022}, author = {Murphy, D}, title = {Invited discussant comments during the UCL-Penn Global COVID Study webinar 'Reflections, Resilience, and Recovery: A qualitative study of Covid-19's impact on an international adult population's mental health and priorities for support': part 3 of 3.}, journal = {UCL open. Environment}, volume = {4}, number = {}, pages = {e007}, pmid = {37228467}, issn = {2632-0886}, abstract = {This discussant commentary considers the findings presented from the UCL-Penn Global COVID Study webinar 'Let's Talk! What do you need to recover from Covid-19?' and published in Wong et al's article in this journal, Reflections, Resilience, and Recovery, drawing into focus the support required to recover from the changes in people's mental health, physical health and relationships brought on by the Covid-19 pandemic. Acknowledging the importance of not making broad generalisations about the effect of the lockdown allows us to see individuals in their own context and their own particular challenges. As we emerge from the Covid-19 pandemic, we need to use the lessons from this study as the foundations for building resilience against future pandemics.}, } @article {pmid37228252, year = {2023}, author = {Liu, X and Qin, T and Li, T and Shan, L and Lei, X and Xu, X and Wen, B and Feng, Y and Yin, P and Fan, D}, title = {"Huoling Shengji granule" for amyotrophic lateral sclerosis: protocol for a multicenter, randomized, double-blind, riluzole parallel controlled clinical trial.}, journal = {Frontiers in aging neuroscience}, volume = {15}, number = {}, pages = {1153973}, pmid = {37228252}, issn = {1663-4365}, abstract = {BACKGROUND: There is still a large demand for effective treatments to delay disease deterioration in amyotrophic lateral sclerosis (ALS). Typical symptoms of ALS are considered "flaccidity syndrome" in traditional Chinese medicine (TCM). Huoling Shengji Granule (HLSJ) is a TCM formula used to treat flaccidity syndrome. Results of preclinical tests and a previous clinical study support HLSJ as a novel drug for ALS patients. This trial proposed to examine whether a 48-week course of HLSJ is effective and safe for ALS patients diagnosed with the Chinese medicine syndrome of spleen qi insufficiency and kidney yang deficiency.

METHODS AND ANALYSIS: In this phase II, multicenter, randomized, double-blind, riluzole parallel-controlled, superiority-design study, eligible participants had the equal opportunity to be assigned to receive either HLSJ or riluzole randomly. Eleven specialized ALS centers in Mainland China will recruit 144 patients for this trial. The primary and secondary outcomes included the change in the ALSFRS-R score and the Rasch-Built Overall Amyotrophic Lateral Sclerosis Disability Scale (ROADS) from baseline to Week 48.

DISCUSSION: Here, we endeavored to evaluate TCM for ALS using a standard evidence-based approach for the first time. In addition, the ROADS, a self-report linear-weighted questionnaire, was selected as a secondary outcome measure. We expect to offer a new reference for the outcome evaluation of ALS trials.Clinical trial registration:http://www.Chictr.org.cn, identifier ChiCTR2100044085.}, } @article {pmid37225489, year = {2024}, author = {Toyoshima, M and Suzuki, N and Mitsuzawa, S and Soga, T and Izumi, R and Mitsui, K and Miyagi, S and Aoki, M and Kato, M}, title = {Amyotrophic Lateral Sclerosis with a Priority Request for a Postmortem Kidney Donation to a Relative.}, journal = {Internal medicine (Tokyo, Japan)}, volume = {63}, number = {2}, pages = {305-307}, pmid = {37225489}, issn = {1349-7235}, mesh = {Male ; Humans ; Middle Aged ; *Amyotrophic Lateral Sclerosis/surgery ; *Tissue and Organ Procurement ; Autopsy ; Kidney ; }, abstract = {The patient was 57 years old when he was diagnosed with amyotrophic lateral sclerosis (ALS) at 1 year after developing bulbar symptoms. At 58 years old, he stated that he was considering donating his kidney to his son suffering from diabetic nephropathy. We confirmed the patient's intentions through repeated interviews before his death at 61 years old. Nephrectomy was performed 30 min after his cardiac death. Organ donation spontaneously proposed by an ALS patient should be considered in order to meet the requests of patients who want their families and other patients to live longer, thereby imparting a beneficial legacy through their deaths.}, } @article {pmid37225320, year = {2023}, author = {Shanker, OR and Kumar, S and Dixit, AB and Banerjee, J and Tripathi, M and Sarat Chandra, P}, title = {Epigenetics of neurological diseases.}, journal = {Progress in molecular biology and translational science}, volume = {198}, number = {}, pages = {165-184}, doi = {10.1016/bs.pmbts.2023.01.006}, pmid = {37225320}, issn = {1878-0814}, mesh = {Humans ; *Nervous System Diseases/genetics ; Epigenesis, Genetic ; *Parkinson Disease/genetics ; DNA Methylation/genetics ; Chromatin ; }, abstract = {Higher-order DNA structure and gene expression are governed by epigenetic processes like DNA methylation and histone modifications. Abnormal epigenetic mechanisms are known to contribute to the emergence of numerous diseases, including cancer. Historically, the chromatin abnormalities were only considered to be limited to discrete DNA sequences and were thought to be associated with rare genetic syndrome however, recent discoveries have pointed to genome-wide level changes in the epigenetic machinery which has contributed to a better knowledge of the mechanisms underlying developmental and degenerative neuronal problems associated with diseases such as Parkinson's disease, Huntington's disease, Epilepsy, Multiple sclerosis, etc. In the given chapter we describe the epigenetic alterations seen in various neurological disorders and further discuss the influence of these epigenetic changes on developing novel therapies.}, } @article {pmid37224600, year = {2023}, author = {Santos Silva, C and Swash, M and de Carvalho, M}, title = {Exploring the split hand phenomenon with the neurophysiological index.}, journal = {Neurophysiologie clinique = Clinical neurophysiology}, volume = {53}, number = {4}, pages = {102864}, doi = {10.1016/j.neucli.2023.102864}, pmid = {37224600}, issn = {1769-7131}, abstract = {In 164 subjects of different age groups, we studied the neurophysiological index (NI) ([CMAP amplitude/Distal motor latency] *[F-wave frequency]; CMAP=compound muscle action potential) for three hand muscles (APB= abductor pollicis brevis; FDI= first dorsal interosseous; ADM= abductor digiti minimi). A split hand index based on CMAP amplitude (SHI_CMAP) and NI (SHI_NI) were calculated ([APB CMAP amplitude or NI * FDI CMAP amplitude or NI]/[ADM CMAP amplitude or NI]). All these neurophysiological measurements differed between age groups (p<0.001). Hand muscle NIs, as well as SHI_NI and SHI_CMAP were age dependent. This may be relevant for diagnostic purposes in motor neuron diseases.}, } @article {pmid37223625, year = {2023}, author = {Mashriqi, F and Mishra, BB and Giliberto, L and Franceschi, AM}, title = {[18] F-FDG Brain PET/MRI in Amyotrophic Lateral Sclerosis- Frontotemporal Spectrum Disorder (ALS-FTSD).}, journal = {World journal of nuclear medicine}, volume = {22}, number = {2}, pages = {135-139}, pmid = {37223625}, issn = {1450-1147}, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal and progressive neurodegenerative disorder involving both upper and lower motor neurons. Interestingly, 15 to 41% of patients with ALS have concomitant frontotemporal dementia (FTD). Approximately, 50% of patients with ALS can copresent with a broader set of neuropsychological pathologies that do not meet FTD diagnostic criteria. This association resulted in revised and expanded criteria establishing the ALS-frontotemporal spectrum disorder (FTSD). In this case report, we review background information, epidemiology, pathophysiology, and structural and molecular imaging features of ALS-FTSD.}, } @article {pmid37223565, year = {2023}, author = {Brotherton, JML and McDermott, T and Smith, MA and Machalek, DA and Shilling, H and Prang, KH and Jennett, C and Nightingale, C and Zammit, C and Pagotto, A and Rankin, NM and Kelaher, M}, title = {Implementation of Australia's primary human papillomavirus (HPV) cervical screening program: The STakeholders Opinions of Renewal Implementation and Experiences Study.}, journal = {Preventive medicine reports}, volume = {33}, number = {}, pages = {102213}, pmid = {37223565}, issn = {2211-3355}, abstract = {In this study, we aimed to document stakeholders' experiences of implementing Australia's renewed National Cervical Screening Program. In December 2017, the program changed from 2nd yearly cytology for 20-69 year olds to 5 yearly human papillomavirus (HPV) screening for women 25-74 years. We undertook semi-structured interviews with key stakeholders including government, program administrators, register staff, clinicians and health care workers, non-government organisations, professional bodies, and pathology laboratories from across Australia between Nov 2018 - Aug 2019. Response rate to emailed invitations was 49/85 (58%). We used Proctor et al's (2011) implementation outcomes framework to guide our questions and thematic analysis. We found that stakeholders were evenly divided over whether implementation was successful. There was strong support for change, but concern over aspects of the implementation. There was some frustration related to the delayed start, timeliness of communication and education, shortcomings in change management, lack of inclusion of Aboriginal and Torres Strait Islander people in planning and implementation, failure to make self-collection widely available, and delays in the National Cancer Screening Register. Barriers centred around a perceived failure to appreciate the enormity of the change and register build, and consequent failure to resource, project manage and communicate effectively. Facilitators included the good will and dedication of stakeholders, strong evidence base for change and the support of jurisdictions during the delay. We documented substantial implementation challenges, offering learnings for other countries transitioning to HPV screening. Sufficient planning, significant and transparent engagement and communication with stakeholders, and change management are critical.}, } @article {pmid37223542, year = {2023}, author = {Ciccarone, F and Castelli, S and Lazzarino, G and Scaricamazza, S and Mangione, R and Bernardini, S and Apolloni, S and D'Ambrosi, N and Ferri, A and Ciriolo, MR}, title = {Lipid catabolism and mitochondrial uncoupling are stimulated in brown adipose tissue of amyotrophic lateral sclerosis mouse models.}, journal = {Genes & diseases}, volume = {10}, number = {2}, pages = {321-324}, pmid = {37223542}, issn = {2352-3042}, } @article {pmid37223130, year = {2023}, author = {Ruf, WP and Boros, M and Freischmidt, A and Brenner, D and Grozdanov, V and de Meirelles, J and Meyer, T and Grehl, T and Petri, S and Grosskreutz, J and Weyen, U and Guenther, R and Regensburger, M and Hagenacker, T and Koch, JC and Emmer, A and Roediger, A and Steinbach, R and Wolf, J and Weishaupt, JH and Lingor, P and Deschauer, M and Cordts, I and Klopstock, T and Reilich, P and Schoeberl, F and Schrank, B and Zeller, D and Hermann, A and Knehr, A and Günther, K and Dorst, J and Schuster, J and Siebert, R and Ludolph, AC and Müller, K}, title = {Spectrum and frequency of genetic variants in sporadic amyotrophic lateral sclerosis.}, journal = {Brain communications}, volume = {5}, number = {3}, pages = {fcad152}, pmid = {37223130}, issn = {2632-1297}, abstract = {Therapy of motoneuron diseases entered a new phase with the use of intrathecal antisense oligonucleotide therapies treating patients with specific gene mutations predominantly in the context of familial amyotrophic lateral sclerosis. With the majority of cases being sporadic, we conducted a cohort study to describe the mutational landscape of sporadic amyotrophic lateral sclerosis. We analysed genetic variants in amyotrophic lateral sclerosis-associated genes to assess and potentially increase the number of patients eligible for gene-specific therapies. We screened 2340 sporadic amyotrophic lateral sclerosis patients from the German Network for motor neuron diseases for variants in 36 amyotrophic lateral sclerosis-associated genes using targeted next-generation sequencing and for the C9orf72 hexanucleotide repeat expansion. The genetic analysis could be completed on 2267 patients. Clinical data included age at onset, disease progression rate and survival. In this study, we found 79 likely pathogenic Class 4 variants and 10 pathogenic Class 5 variants (without the C9orf72 hexanucleotide repeat expansion) according to the American College of Medical Genetics and Genomics guidelines, of which 31 variants are novel. Thus, including C9orf72 hexanucleotide repeat expansion, Class 4, and Class 5 variants, 296 patients, corresponding to ∼13% of our cohort, could be genetically resolved. We detected 437 variants of unknown significance of which 103 are novel. Corroborating the theory of oligogenic causation in amyotrophic lateral sclerosis, we found a co-occurrence of pathogenic variants in 10 patients (0.4%) with 7 being C9orf72 hexanucleotide repeat expansion carriers. In a gene-wise survival analysis, we found a higher hazard ratio of 1.47 (95% confidence interval 1.02-2.1) for death from any cause for patients with the C9orf72 hexanucleotide repeat expansion and a lower hazard ratio of 0.33 (95% confidence interval 0.12-0.9) for patients with pathogenic SOD1 variants than for patients without a causal gene mutation. In summary, the high yield of 296 patients (∼13%) harbouring a pathogenic variant and oncoming gene-specific therapies for SOD1/FUS/C9orf72, which would apply to 227 patients (∼10%) in this cohort, corroborates that genetic testing should be made available to all sporadic amyotrophic lateral sclerosis patients after respective counselling.}, }